E. coli - A Medical Dictionary, Bibliography, and Annotated Research Guide to Internet References

COLI A M EDICAL D ICTIONARY , B IBLIOGRAPHY , AND A NNOTATED R ESEARCH G UIDE TO I NTERNET R E FERENCES J AMES N. P ARK...

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COLI A M EDICAL D ICTIONARY , B IBLIOGRAPHY , AND A NNOTATED R ESEARCH G UIDE TO I NTERNET R E FERENCES

J AMES N. P ARKER , M.D. AND P HILIP M. P ARKER , P H .D., E DITORS

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ICON Health Publications ICON Group International, Inc. 4370 La Jolla Village Drive, 4th Floor San Diego, CA 92122 USA Copyright 2003 by ICON Group International, Inc. Copyright 2003 by ICON Group International, Inc. All rights reserved. This book is protected by copyright. No part of it may be reproduced, stored in a retrieval system, or transmitted in any form or by any means, electronic, mechanical, photocopying, recording, or otherwise, without written permission from the publisher. Printed in the United States of America. Last digit indicates print number: 10 9 8 7 6 4 5 3 2 1

Publisher, Health Care: Philip Parker, Ph.D. Editor(s): James Parker, M.D., Philip Parker, Ph.D. Publisher's note: The ideas, procedures, and suggestions contained in this book are not intended for the diagnosis or treatment of a health problem. As new medical or scientific information becomes available from academic and clinical research, recommended treatments and drug therapies may undergo changes. The authors, editors, and publisher have attempted to make the information in this book up to date and accurate in accord with accepted standards at the time of publication. The authors, editors, and publisher are not responsible for errors or omissions or for consequences from application of the book, and make no warranty, expressed or implied, in regard to the contents of this book. Any practice described in this book should be applied by the reader in accordance with professional standards of care used in regard to the unique circumstances that may apply in each situation. The reader is advised to always check product information (package inserts) for changes and new information regarding dosage and contraindications before prescribing any drug or pharmacological product. Caution is especially urged when using new or infrequently ordered drugs, herbal remedies, vitamins and supplements, alternative therapies, complementary therapies and medicines, and integrative medical treatments. Cataloging-in-Publication Data Parker, James N., 1961Parker, Philip M., 1960E. coli: A Medical Dictionary, Bibliography, and Annotated Research Guide to Internet References / James N. Parker and Philip M. Parker, editors p. cm. Includes bibliographical references, glossary, and index. ISBN: 0-597-83899-2 1. E. coli-Popular works. I. Title.

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Disclaimer This publication is not intended to be used for the diagnosis or treatment of a health problem. It is sold with the understanding that the publisher, editors, and authors are not engaging in the rendering of medical, psychological, financial, legal, or other professional services. References to any entity, product, service, or source of information that may be contained in this publication should not be considered an endorsement, either direct or implied, by the publisher, editors, or authors. ICON Group International, Inc., the editors, and the authors are not responsible for the content of any Web pages or publications referenced in this publication.

Copyright Notice If a physician wishes to copy limited passages from this book for patient use, this right is automatically granted without written permission from ICON Group International, Inc. (ICON Group). However, all of ICON Group publications have copyrights. With exception to the above, copying our publications in whole or in part, for whatever reason, is a violation of copyright laws and can lead to penalties and fines. Should you want to copy tables, graphs, or other materials, please contact us to request permission (E-mail: [email protected]). ICON Group often grants permission for very limited reproduction of our publications for internal use, press releases, and academic research. Such reproduction requires confirmed permission from ICON Group International Inc. The disclaimer above must accompany all reproductions, in whole or in part, of this book.

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Acknowledgements The collective knowledge generated from academic and applied research summarized in various references has been critical in the creation of this book which is best viewed as a comprehensive compilation and collection of information prepared by various official agencies which produce publications on E. coli. Books in this series draw from various agencies and institutions associated with the United States Department of Health and Human Services, and in particular, the Office of the Secretary of Health and Human Services (OS), the Administration for Children and Families (ACF), the Administration on Aging (AOA), the Agency for Healthcare Research and Quality (AHRQ), the Agency for Toxic Substances and Disease Registry (ATSDR), the Centers for Disease Control and Prevention (CDC), the Food and Drug Administration (FDA), the Healthcare Financing Administration (HCFA), the Health Resources and Services Administration (HRSA), the Indian Health Service (IHS), the institutions of the National Institutes of Health (NIH), the Program Support Center (PSC), and the Substance Abuse and Mental Health Services Administration (SAMHSA). In addition to these sources, information gathered from the National Library of Medicine, the United States Patent Office, the European Union, and their related organizations has been invaluable in the creation of this book. Some of the work represented was financially supported by the Research and Development Committee at INSEAD. This support is gratefully acknowledged. Finally, special thanks are owed to Tiffany Freeman for her excellent editorial support.

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About the Editors James N. Parker, M.D. Dr. James N. Parker received his Bachelor of Science degree in Psychobiology from the University of California, Riverside and his M.D. from the University of California, San Diego. In addition to authoring numerous research publications, he has lectured at various academic institutions. Dr. Parker is the medical editor for health books by ICON Health Publications. Philip M. Parker, Ph.D. Philip M. Parker is the Eli Lilly Chair Professor of Innovation, Business and Society at INSEAD (Fontainebleau, France and Singapore). Dr. Parker has also been Professor at the University of California, San Diego and has taught courses at Harvard University, the Hong Kong University of Science and Technology, the Massachusetts Institute of Technology, Stanford University, and UCLA. Dr. Parker is the associate editor for ICON Health Publications.

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About ICON Health Publications To discover more about ICON Health Publications, simply check with your preferred online booksellers, including Barnes & Noble.com and Amazon.com which currently carry all of our titles. Or, feel free to contact us directly for bulk purchases or institutional discounts: ICON Group International, Inc. 4370 La Jolla Village Drive, Fourth Floor San Diego, CA 92122 USA Fax: 858-546-4341 Web site: www.icongrouponline.com/health

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Table of Contents FORWARD .......................................................................................................................................... 1 CHAPTER 1. STUDIES ON E. COLI ...................................................................................................... 3 Overview........................................................................................................................................ 3 The Combined Health Information Database................................................................................. 3 Federally Funded Research on E. coli ............................................................................................ 7 E-Journals: PubMed Central ....................................................................................................... 67 The National Library of Medicine: PubMed .............................................................................. 103 CHAPTER 2. NUTRITION AND E. COLI .......................................................................................... 149 Overview.................................................................................................................................... 149 Finding Nutrition Studies on E. coli ......................................................................................... 149 Federal Resources on Nutrition ................................................................................................. 160 Additional Web Resources ......................................................................................................... 160 CHAPTER 3. ALTERNATIVE MEDICINE AND E. COLI .................................................................... 163 Overview.................................................................................................................................... 163 National Center for Complementary and Alternative Medicine................................................ 163 Additional Web Resources ......................................................................................................... 170 General References ..................................................................................................................... 175 CHAPTER 4. DISSERTATIONS ON E. COLI ...................................................................................... 177 Overview.................................................................................................................................... 177 Dissertations on E. coli .............................................................................................................. 177 Keeping Current ........................................................................................................................ 187 CHAPTER 5. CLINICAL TRIALS AND E. COLI ................................................................................. 189 Overview.................................................................................................................................... 189 Recent Trials on E. coli .............................................................................................................. 189 Keeping Current on Clinical Trials ........................................................................................... 190 CHAPTER 6. PATENTS ON E. COLI ................................................................................................. 193 Overview.................................................................................................................................... 193 Patents on E. coli ....................................................................................................................... 193 Patent Applications on E. coli.................................................................................................... 228 Keeping Current ........................................................................................................................ 240 CHAPTER 7. BOOKS ON E. COLI..................................................................................................... 241 Overview.................................................................................................................................... 241 Book Summaries: Federal Agencies............................................................................................ 241 Book Summaries: Online Booksellers......................................................................................... 242 The National Library of Medicine Book Index ........................................................................... 243 Chapters on E. coli ..................................................................................................................... 245 CHAPTER 8. MULTIMEDIA ON E. COLI .......................................................................................... 247 Overview.................................................................................................................................... 247 Video Recordings ....................................................................................................................... 247 Bibliography: Multimedia on E. coli .......................................................................................... 248 CHAPTER 9. PERIODICALS AND NEWS ON E. COLI ....................................................................... 251 Overview.................................................................................................................................... 251 News Services and Press Releases.............................................................................................. 251 Academic Periodicals covering E. coli........................................................................................ 253 CHAPTER 10. RESEARCHING MEDICATIONS................................................................................. 255 Overview.................................................................................................................................... 255 U.S. Pharmacopeia..................................................................................................................... 255 Commercial Databases ............................................................................................................... 256 Researching Orphan Drugs ....................................................................................................... 256 APPENDIX A. PHYSICIAN RESOURCES .......................................................................................... 261 Overview.................................................................................................................................... 261

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NIH Guidelines.......................................................................................................................... 261 NIH Databases........................................................................................................................... 263 Other Commercial Databases..................................................................................................... 265 The Genome Project and E. coli ................................................................................................. 265 APPENDIX B. PATIENT RESOURCES ............................................................................................... 271 Overview.................................................................................................................................... 271 Patient Guideline Sources.......................................................................................................... 271 Finding Associations.................................................................................................................. 276 APPENDIX C. FINDING MEDICAL LIBRARIES ................................................................................ 279 Overview.................................................................................................................................... 279 Preparation................................................................................................................................. 279 Finding a Local Medical Library................................................................................................ 279 Medical Libraries in the U.S. and Canada ................................................................................. 279 ONLINE GLOSSARIES................................................................................................................ 285 Online Dictionary Directories ................................................................................................... 285 E. COLI DICTIONARY................................................................................................................. 287 INDEX .............................................................................................................................................. 373

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FORWARD In March 2001, the National Institutes of Health issued the following warning: "The number of Web sites offering health-related resources grows every day. Many sites provide valuable information, while others may have information that is unreliable or misleading."1 Furthermore, because of the rapid increase in Internet-based information, many hours can be wasted searching, selecting, and printing. Since only the smallest fraction of information dealing with E. coli is indexed in search engines, such as www.google.com or others, a nonsystematic approach to Internet research can be not only time consuming, but also incomplete. This book was created for medical professionals, students, and members of the general public who want to know as much as possible about E. coli, using the most advanced research tools available and spending the least amount of time doing so. In addition to offering a structured and comprehensive bibliography, the pages that follow will tell you where and how to find reliable information covering virtually all topics related to E. coli, from the essentials to the most advanced areas of research. Public, academic, government, and peer-reviewed research studies are emphasized. Various abstracts are reproduced to give you some of the latest official information available to date on E. coli. Abundant guidance is given on how to obtain free-of-charge primary research results via the Internet. While this book focuses on the field of medicine, when some sources provide access to non-medical information relating to E. coli, these are noted in the text. E-book and electronic versions of this book are fully interactive with each of the Internet sites mentioned (Clicking on a hyperlink automatically opens your browser to the site indicated). If you are using the hard copy version of this book, you can access a cited Web site by typing the provided Web address directly into your Internet browser. You may find it useful to refer to synonyms or related terms when accessing these Internet databases. NOTE: At the time of publication, the Web addresses were functional. However, some links may fail due to URL address changes, which is a common occurrence on the Internet. For readers unfamiliar with the Internet, detailed instructions are offered on how to access electronic resources. For readers unfamiliar with medical terminology, a comprehensive glossary is provided. For readers without access to Internet resources, a directory of medical libraries, that have or can locate references cited here, is given. We hope these resources will prove useful to the widest possible audience seeking information on E. coli. The Editors

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From the NIH, National Cancer Institute (NCI): http://www.cancer.gov/cancerinfo/ten-things-to-know.

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CHAPTER 1. STUDIES ON E. COLI Overview In this chapter, we will show you how to locate peer-reviewed references and studies on E. coli.

The Combined Health Information Database The Combined Health Information Database summarizes studies across numerous federal agencies. To limit your investigation to research studies and E. coli, you will need to use the advanced search options. First, go to http://chid.nih.gov/index.html. From there, select the “Detailed Search” option (or go directly to that page with the following hyperlink: http://chid.nih.gov/detail/detail.html). The trick in extracting studies is found in the drop boxes at the bottom of the search page where “You may refine your search by.” Select the dates and language you prefer, and the format option “Journal Article.” At the top of the search form, select the number of records you would like to see (we recommend 100) and check the box to display “whole records.” We recommend that you type “E. coli” (or synonyms) into the “For these words:” box. Consider using the option “anywhere in record” to make your search as broad as possible. If you want to limit the search to only a particular field, such as the title of the journal, then select this option in the “Search in these fields” drop box. The following is what you can expect from this type of search: •

Escherichia Coli as a Cause of Diarrhea Source: Journal of Gastroenterology and Hepatology. 17(4): 467-475. April 2002. Contact: Available from Blackwell Science. 54 University Street, Carlton South 3053, Victoria, Australia. +61393470300. Fax +61393475001. E-mail: [email protected]. Website: www.blackwell-science.com. Summary: Escherichia coli is the best known member of the normal microbiota of the human intestine and a versatile gastrointestinal pathogen (Cause of disease). This article explores the role of E. coli as a cause of diarrhea. The varieties of E. coli that cause diarrhea are classified into named pathotypes, including enterotoxigenic, enteroinvasive, enteropathogenic, and enterohemorrhagic. Individual strains of each pathotype possess a distinct set of virulence-associated characteristics that determine the

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clinical, pathological and epidemiological features of the diseases they cause. In the article, the authors summarize the key distinguishing features of the major pathotypes of diarrhea-genic E. coli. Knowledge of the pathogenic mechanisms of these bacteria has led to the development of rational interventions for the treatment and prevention of E. coli induced diarrhea. The mainstay of antidiarrheal therapy is oral rehydration with sugar and electrolyte solutions. Importantly, patients suspected of being infected with these bacteria should not be treated with antibiotics because these may enhance toxin synthesis or promote its release from the bacteria with a consequent increased risk of hemorrhagic colitis. 4 figures. 4 tables. 59 references. •

Escherichia Coli O157: H7 and the Hemolytic-Uremic Syndrome Source: New England Journal of Medicine. 333(6): 364-368. August 10, 1995. Summary: In this article, the authors consider the relationship between Escherichia coli O157: H7 and the hemolytic-uremic syndrome (HUS). Topics include the epidemiology of E. coli O157: H7, including incidence, geographic and seasonal factors, and transmission; pathophysiology and immunity; clinical manifestations; diagnosis; treatment; and recognition of and response to outbreaks. The authors note that several studies have shown that infection with E. coli O157: H7 is responsible for most cases of HUS, a major cause of acute renal failure in children. 2 figures. 1 table. 60 references.

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Escherichia Coli O157: H7 Infection in Humans Source: Annals of Internal Medicine. 123(9): 698-714. November 1, 1995. Summary: In this article, the authors review the clinical relevance of Escherichia coli 0157: H7 infection, including the epidemiology of the infection and its clinical presentations, pathogenesis, microbiology, diagnosis, treatment, and prevention. All articles and case reports in MEDLINE or the bibliographies of relevant articles describing E. coli 0157: H7 were selected. The data synthesis showed that infection with E. coli 0157: H7 presents with a wide spectrum of clinical manifestations, including the hemolytic-uremic syndrome and thrombotic thrombocytopenic purpura. Patients at extremes of age have an increased risk for infection and associated complications. Transmission of E. coli 0157: H7 is primarily foodborne, with undercooked meat the most common culprit. Treatment is primarily supportive and includes the management of complications as necessary. The authors conclude that development of the hemolyticuremic syndrome or thrombotic thrombocytopenia purpura should raise strong suspicion of E. coli 0157: H7 infection and should lead to prompt evaluation. 3 figures. 217 references. (AA-M).

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Intestinal Epithelial Cell Protein Phosphorylation in Enteropathogenic Escherichia Coli Diarrhoea Source: Lancet. Volume 339. February 29, 1992. p. 521-523. Summary: The ability of enteropathogenic Escherichia coli (EPEC) to cause diarrhea in man is associated with the formation of characteristic histopathological lesions in smallintestine enterocytes, with gross cytoskeletal damage and loss of brush-border microvilli. This article reports on research into enterocyte protein phosphorylation in response to EPEC infection. Results showed that the major protein is myoxin light-chain, an important cytoskeletal protein known to affect actin organization in non-muscle cells. The authors hypothesize about the role of EPEC-induced phosphorylation of other cell proteins in the mechanism of secretory EPEC diarrhea. 10 references. (AA-M).

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Uropathogenic Escherichia Coli Causing Urinary Tract Infections Source: Indian Journal of Medical Research. 114: 207-211. December 2001. Contact: Available from Medical Economics. 5 Paragon Drive, Montvale, NJ 07645. (800) 432-4570. Fax (201) 573-4956. Summary: The information on the characteristics of Escherichia coli causing urinary tract infections (UTIs) is limited. This article reports on a study that characterized the urovirulence factors of E. coli isolated from symptomatic patients with UTIs in order to determine their pathogenic (disease causing) potential and the antibody sensitivity profile. Semi-quantitative urine culture was done on 370 symptomatic patients suffering from UTIs. Phenotypic characterization of the urovirulence factors of E. coli was undertaken and the antibiotic susceptibility was determined. E. coli was responsible for 45.5 percent of infections. Resistance to amoxicillin, clotrimoxazole nalidixic acid, norfloxacin, and ciprofloxacin among E. coli isolates ranged from 70 to 95 percent. Serotype O101 was found to be the most common serotype (7 of 26). The authors conclude that antibiotic resistance was high among the strains circulating which emphasizes the need for judicious use of antibiotics. Certain virulence factors like hemolysin production and presence of fimbriae in the E. coli may be associated with the urovirulence. 1 figure. 17 references.

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Widespread Distribution of Urinary Tract Infections Caused by A MultidrugResistant Escherichia Coli Clonal Group Source: New England Journal of Medicine. 345(14): 1007-1013. October 4, 2001. Summary: The management of urinary tract infections (UTIs) is complicated by the increasing prevalence of antibiotic-resistant strains of Escherichia coli. This article reports on a study of the clonal composition of E. coli isolates that were resistant to trimethoprim-sulfamethoxazole from women with community-acquired UTIs. Of the 255 E. coli isolates, 55 (22 percent) from a California university cohort were resistant to trimethoprim-sulfamethoxazole as well as to other antibiotics. There was a common pattern of DNA fingerprinting, suggesting that the isolates belonged to the same clonal group (Clonal group A), in 28 of 55 isolates with trimethoprim-sulfamethoxazole resistance (51 percent) and in 2 of randomly selected isolates that were susceptible to trimethoprim-sulfamethoxazole. In addition, 11 of 29 resistant isolates (38 percent) from a Michigan cohort and 7 of 18 (39 percent) from a Minnesota cohort belonged to clonal group A. The authors conclude that in three geographically diverse communities, a single clonal group accounted for nearly half of community-acquired UTIs in women that were caused by E. coli strains with resistance to trimethoprim-sulfamethoxazole. The widespread distribution and high prevalence of E. coli clonal group A have major public health implications. 2 figures. 3 tables. 37 references.

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Association Between Use of Spermicide-Coated Condoms and Escherichia Coli Urinary Tract Infection in Young Women Source: American Journal of Epidemiology. 144(5): 512-520. September 1, 1996. Summary: The use of a diaphragm with spermicide increases the risk of urinary tract infection (UTI) in women. To determine whether spermicide-coated condoms are also associated with an increased risk of UTI, the authors of this article conducted a casecontrol study at a large health maintenance organization in Seattle, Washington. Cases were sexually active young women with acute UTI caused by Escherichia coli, identified from computerized laboratory files from 1990 to 1993. Age-matched controls were

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randomly selected from the enrollment files of the plan. Of 1,904 eligible women, 604 cases and 629 controls (65 percent) were interviewed. During the previous year, 40 percent of the cases and 31 percent of the controls had been exposed to any type of condom. Exposure to spermicide-coated condoms conferred a higher risk of UTI. In multivariate analyses, intercourse frequency, history of UTI, and frequency of spermicide-coated condom exposure were independent predictors of UTI. Spermicidecoated condoms were responsible for 42 percent of the UTIs among women who were exposed to these products. 1 figure. 5 tables. 20 references. (AA-M). •

E. coli 0157:H7-Associated Diarrhea and the Hemolytic Uremic Syndrome Source: Dialysis and Transplantation. 25(4): 205-208, 226. April 1996. Contact: Available from Creative Age Publications, Inc. P.O. Box 15757, N. Hollywood, CA 91615. (800) 624-4196 or (818) 760-8983. Summary: This article explores Escherichia coli-associated diarrhea and the hemolytic uremic syndrome (HUS). The author reviews this condition, looks at factors in the emergence of E. coli as a pathogen, and discusses possible ways to control further outbreaks of the disease. Topics include symptoms of HUS, the epidemiologic history of E. coli-related HUS, transmission of the disease, the role of antibiotics in the emergence of E. coli as a pathogen, E. coli 0157:H7 and how it causes HUS, treatment of E. coli 0157:H7, and prevention of E. coli-associated disease. 1 table. 24 references. (AA-M).

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How to Outsmart Dangerous E. coli Strain Source: FDA Consumer. 28(1): 7-11. January-February 1994. Contact: Available from U.S. Food and Drug Administration. HFI-40, 5600 Fishers Lane, Rockville, MD 20857. Summary: This consumer education article familiarizes readers with a rare but dangerous type of the escherichia coli bacterium, E. coli O157: H7. The article provides information about the 1993 outbreak of E. coli infection in Washington and California; E. coli contamination of apple cider; beneficial strains of E. coli; use of E. coli as an indicator of contamination; development of hemolytic uremic syndrome (HUS) from E. coli O157: H7; symptoms of HUS; temperature levels (from cooking) that kill E. coli O157: H7; transmission; diagnostic tests; and ongoing work on techniques to ensure food safety. 2 figures.

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Escherichia Coli O157:H7 Infection Source: American Family Physician. 56(3): 859-861. September 1, 1997. Contact: Available from American Academy of Family Physicians. 11400 Tomahawk Creek Parkway, Leawood, KS 66211-2672. (800) 274-2237. Website: www.aafp.org. Summary: This three page fact sheet reviews basic information about Escherichia coli O157:H7 infection and how to prevent it. E. coli is the name of a strain of bacteria that causes severe gastroenteritis (Cramps and diarrhea). E. coli is one of the leading causes of bloody diarrhea. The symptoms are worse in children and older people, and especially in people who have another illness. Written in a question and answer format, the fact sheet covers how E. coli infection is transmitted, the symptoms of E. coli infection, complications arising from E. coli infection, diagnostic strategies for establishing E. coli infection, treatment options, and ways to prevent infection with E. coli. The most common way to get this infection is by eating rare (undercooked)

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hamburgers. The germ can also be passed from person to person in day care centers and nursing homes. The most common complication of E. coli infection is hemolytic uremic syndrome (HUS), which consists of hemolytic anemia (low red blood cell count), thrombocytopenia (low platelet count), and renal (kidney) failure. A stool culture is required to confirm E. coli infection. There is no special treatment for E. coli infection, except hydration (drinking a lot of water) and watching for complications. The fact sheet lists rules to follow to prevent contracting foodborne infections such as E. coli. These rules cover handwashing techniques, cooking meat thoroughly, defrosting meats safely, and handling leftovers properly. The fact sheet is also available online. •

Adherence of Type 1-Fimbriated Escherichia Coli to Uroepithelial Cells: More in Diabetic Women Than in Control Subjects Source: Diabetes Care. 25(8): 1405-1409. August 2002. Contact: Available from American Diabetes Association. 1701 North Beauregard Street, Alexandria, VA 22311. (800) 232-3472. Website: www.diabetes.org. Summary: Women with diabetes have bacteriuria (bacteria in the urine) more often than women without diabetes. Because Escherichia coli adhere better to vaginal cells of nondiabetic patients with recurrent urinary tract infections (UTIs) than to those obtained from healthy control subjects, the authors of this study hypothesized that E. coli adhere more to the uroepithelial cells of women with diabetes. This may happen because of substances excreted in the urine (e.g., albumin, glucose, and Tamm Horsfall protein) or because of a difference in the uroepithelial cells of the women with diabetes. The study involved a T24 bladder cell line and uroepithelial cells of 25 women with diabetes and 19 control subjects that were incubated with three different E. coli strains. The mean numbers of type 1-fimbriated (with fringe-like projections) E. coli that adhered to diabetes and control cells were 12.9 and 6.1 respectively, whereas those of P-fimbriated E. coli were 8.8 and 8.1, and those of nonfimbriated E. coli were 2.7 and 3.4. The addition of various substances did not influence the adherence of E. coli to a T24 bladder cell line. The authors conclude that type 1-fimbriated E. coli adhere more to diabetic than to control uroepithelial cells. 2 figures. 28 references.

Federally Funded Research on E. coli The U.S. Government supports a variety of research studies relating to E. coli. These studies are tracked by the Office of Extramural Research at the National Institutes of Health.2 CRISP (Computerized Retrieval of Information on Scientific Projects) is a searchable database of federally funded biomedical research projects conducted at universities, hospitals, and other institutions. Search the CRISP Web site at http://crisp.cit.nih.gov/crisp/crisp_query.generate_screen. You will have the option to perform targeted searches by various criteria, including geography, date, and topics related to E. coli. For most of the studies, the agencies reporting into CRISP provide summaries or abstracts. As opposed to clinical trial research using patients, many federally funded studies use 2

Healthcare projects are funded by the National Institutes of Health (NIH), Substance Abuse and Mental Health Services (SAMHSA), Health Resources and Services Administration (HRSA), Food and Drug Administration (FDA), Centers for Disease Control and Prevention (CDCP), Agency for Healthcare Research and Quality (AHRQ), and Office of Assistant Secretary of Health (OASH).

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animals or simulated models to explore E. coli. The following is typical of the type of information found when searching the CRISP database for E. coli: •

Project Title: BACTERIAL INTERACTIONS WITH THE BLADDER MUCOSA Principal Investigator & Institution: Mulvey, Matthew A.; Pathology; University of Utah 200 S University St Salt Lake City, Ut 84112 Timing: Fiscal Year 2001; Project Start 01-APR-2001; Project End 31-MAR-2003 Summary: (adapted from application abstract): This is a study of host- pathogen interactions at the molecular level, specifically the structural functional relationship of bacterial attachment to host epithelial cells. Urinary tract infections (UTIs) affect a large proportion of the world population and account for significant morbidity and high medical costs. Escherichia coli is the etiologic agent in the majority of all UTIs, including cyctitis. Other members of the Enterobacteriaceae family, including Klebsiella species and Proteus mitabilis, and Gram-positive organisms, including Staphylococcus saprophyticus and opportunistic enterococci species, are also associated with UTIs. To act as pathogens, these various bacteria must first adhere to host mucosal surfaces within the urinary tract. Without the ability to specifically adhere to host tissues, these pathogens would be readily expelled from the host and disease would not occur. Bacterial attachment can initiate a cascade of molecular crosstalk between bacterial and host cells that can directly influence the course of an infection. Virtually all uropathogenic strains of E. coli and most members of the Enterobacteriaceae family encode filamentous surface adhesive organelles called type 1 pili. These structures can mediate bacterial attachment to bladder epithelial cells by interacting with host receptor complexes comprised of integral membrane proteins known as uroplakins. The candidate proposes to use type 1-piliated uropathogenic E. coli as a model to study the structural basis of bacterial attachment and the functional consequences of the attachment event. The specifics of the interactions between type 1 pili and uroplakin receptor complexes will be examined. In addition, the bacterial and host factors that come into play as a consequence of bacterial adherence and influence the pathogenesis of UTIs will be analyzed at both the cellular and molecular level. This work will lead to enhanced understanding of pathogenic processes both within the urinary tract and at other sites of microbial entry and will facilitate the development of novel antimicrobial therapeutics and vaccines. The specific aims are to: 1.Characterize interactions between type 1 pili and the uroplakin receptor complexes that coat the lumenal surface of the bladder. Mutational analysis of recombinant uroplakin protein complexes and of type 1 pili along with biochemical, microscopic, and crystallographic techniques will provide detailed insight into the host-pathogen interactions involved in the establishment of UTIs by uropathogenic E. coli. 2.Investigate virulence factors and mechanisms that enable uropathogenic E. coli to invade, disseminate, and persist within the bladder following the initial attachment event mediated by type 1 pili. The possibility that recurrent UTIs may, in some cases, be a manifestation of a lingering chronic infection will be tested. 3.Elucidate host responses to uropathogenic E. coli, including the identification and characterization of innate and adaptive host defenses that function to limit and clear invading bacteria from the urinary tract. Cell culture systems and a murine cystitis model will be used to delineate vital constituents of an effective host response to infection by type 1-piliated E. coli. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen

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Project Title: BENZO[A] PYRENE MUTAGENIC MECHANISMS Principal Investigator & Institution: Loechler, Edward L.; Professor; Biology; Boston University Charles River Campus 881 Commonwealth Avenue Boston, Ma 02215 Timing: Fiscal Year 2001; Project Start 30-JUN-1985; Project End 31-AUG-2005 Summary: (provided by applicant): Benzo[a]pyrene is a potent mutagen/carcinogen found ubiquitously in the environment. It is metabolically activated inside cells to its (+)-anti-7,8-diol-9,10-epoxide giving adducts principally at N2-Gua ([+ta]-B[a]P-N2-dG). Applicant showed that (+)-anti-B[a]PDE induces base substitution, frameshifts, insertions and deletions (studied in E. coli). The question he is addressing is: how does (+)-anti-B[a]PDE induce such a diverse array of mutations? His working hypothesis is that adduct mutational complexity is due to adduct conformational complexity and that the major adduct ([+ta]-B[a]P-N2-Gua) is able to induce the majority of these mutations. Furthermore, adduct conformation may be controlled by various factors, notably, DNA sequence context. We have generated additional data to support his working hypothesis, and have found that [+ta]-B[a]P-N2-dG principally follows the G->T mutational pathway in 5'-TGC sequences (>95 percent), but principally the G->A mutational pathway in a 5'-AGA ( about95 percent) and a 5'-CGY ( about80 percent) sequence context. A correlation between his mutagenesis findings and molecular modeling studies (funded separately) suggested a conformational hypothesis for the induction of G->T vs. G->A mutation. Preliminary findings suggest that this hypothesis is probably not correct. He believes that more data are needed on the effect of DNA sequence context on [+ta]-B[a]P-N2-dG mutagenesis before another hypothesis can be proposed. In addition, he believes that one must understand what polymerase is involved in mutagenic bypass. To this end, three specific aims are proposed. (1) The mutagenic patterns for [+ta]-B[a]P-N2-dG in a 5'-TGT vs. a 5'-UGT context and a 5'm5CGT- vs. a 5'-CGT context will be compared to evaluate the role of a methyl group on the base to the 5'-side of the adduct to influence the pattern of mutagenesis. This aim relates to a hypothesis for why G->T mutations are high in 5'-TG sequences. (2) [+ta]B[a]P-N2-dG will be studied in all combinations of sequence contexts 5'-XGY from which sequence context rules for mutagenesis will emerge. These rules (in combination with structural/conformational studies) will be used to generate new ideas for how adduct conformations might induce (e.g.) G->T vs. G->A mutations. The vector in this study will permit the applicant to do studies in both E. coli and human cells in culture. (3) Investigate what E. coli DNA polymerase(s) (notably, DNA polymerases II, IV, V, or UVM) is (are) responsible for G->T vs. G->A mutations for [+ta]-B[a]P-N2-dG. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen

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Project Title: BIOCHEMICAL BASIS OF SOS--INDUCED MUTAGENESIS Principal Investigator & Institution: Goodman, Myron F.; Professor; Biological Sciences; University of Southern California 2250 Alcazar Street, Csc-219 Los Angeles, Ca 90033 Timing: Fiscal Year 2001; Project Start 01-JUL-1989; Project End 31-MAR-2003 Summary: (adapted from investigator's abstract): The broad objective of this grant application is to investigate how damaged DNA is copied by the cell's replication and repair enzymes, focusing on proteins that are induced in response to DNA damage. Damage-induced DNA repair occurs in both procaryotic and eucaryotic organisms. In Escherichia coli, response to DNA damage is orchestrated by an operon, the "SOS regulon", containing at least 25 different proteins under negative control of a repressor protein, LexA, and a multifunctional protein, RecA. In E. coli, and seemingly in animal cells as well, damage-induced DNA repair is aberrant. There is a reduction in fidelity

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which enables replication to continue past blocking DNA damage sites. The primary goal of this proposal is to elucidate the biochemical basis for SOS-induced error- prone repair in E. coli. Such repair depends on an activated form of RecA (RecA*) interacting with a mutagenic UmuD'2C protein complex. There are numerous types of damage occurring in DNA when cells are exposed to chemicals, drugs or radiation. To study error-prone repair in vitro and in vivo, Dr. Goodman has chosen to focus primarily on copying a site- directed abasic (apurinic/apyrimidinic) DNA lesion, a biologically relevant noncoding lesion that can occur by spontaneous and induced mechanisms. The absence of a coding base in DNA presents a strong block to replication. When replication past an abasic lesion does occur, it often results in a mutation. In this proposal, he will quantify the effects of damage-induced repair proteins in E. coli, specifically UmuD'2C, RecA*, DNA polymerase III holoenzyme, and SSB, on nucleotide insertion and excision (proofreading) at the site of the lesion, and bypass of the lesion. During the previous grant period, he succeeded in purifying UmuD'2C in soluble, active form, and showed that the complex, in the presence of RecA*, efficiently catalyzed lesion bypass. An unexpected result was that UmuD'2C catalyzed lesion bypass in the apparent absence of the polymerizing subunit of pol III holoenzyme. In other words, it is possible that UmuD'2C complex has its own low fidelity polymerase activity. If this surprising observation can be sustained, it would then have major impact in explaining how damaged DNA is copied in procaryotic and eucaryotic organisms. E. coli DNA polymerase II, is also induced in response to DNA damage, as part of the SOS regulon, but does not appear to take part in the UmuD2C - RecA* error-prone repair pathway. Another important goal is to examine the role of pol III in a UmuD'2C-independent pathway for repair of DNA damaged by exposure to ultraviolet radiation. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •

Project Title: BIOPHYSICAL CHEMISTRY OF A DEAD/H PROTEIN Principal Investigator & Institution: Uhlenbeck, Olke C.; Board of Trustees Professor; Chemistry and Biochemistry; University of Colorado at Boulder Boulder, Co 80309 Timing: Fiscal Year 2001; Project Start 01-JUN-2000; Project End 31-MAY-2004 Summary: (From the Applicant's Abstract) The goal of this project is to obtain an understanding of the function of E. coli DbpA, a member of the large DEAD/H family of proteins that participate in many cellular pathways involving RNA. DEAD/H proteins couple the hydrolysis of ATP with RNA binding and are proposed to modify RNA secondary and tertiary structure. E. coli DbpA and its B. subtilis homologue YxiN were chosen for detailed structural and mechanistic studies because, unlike nearly all other DEAD/H proteins, they bind tightly and specifically to a discrete region of 23S rRNA. The equilibrium and rate constants for the steps in the minimal kinetic scheme of the ATPase reaction will be determined to establish a framework for structure-function studies. The possibility that DbpA acts as a helicase in restructuring rRNA will be examined. RNA modification, photocrosslinking, and protein engineering experiments will test how different domains of DbpA interact with its cognate RNA, and whether the protein-RNA contacts change during the catalytic cycle. Finally, a DbpA disruption strain of E. coli will be used to search for the mechanism of action of DbpA in E. coli cells. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen

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Project Title: BIOSYNTHESIS AND FUNCTION OF LIPOPOLYSACCHARIDES Principal Investigator & Institution: Raetz, Christian R.; Professor & Chairman; Biochemistry; Duke University Durham, Nc 27706

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Timing: Fiscal Year 2002; Project Start 01-SEP-1994; Project End 31-JUL-2006 Summary: (provided by applicant): The outer leaflet of the outer membranes of Gramnegative bacteria is covered with a remarkable glycolipid known as lipopolysaccharide (LPS). In Escherichia coli, the lipid A anchor of LPS is a hexa-acylated disaccharide of glucosamine, bearing phosphate groups at the 1 and 4' positions. The minimal LPS required for growth of E. coli contains lipid A and Kdo sugars. The biosynthesis of lipid A is well characterized. Inhibition of any one of the enzymes catalyzing the first seven steps of the pathway in E. coil causes cell death. Lipid A is therefore an interesting target for designing new antibacterial agents. Emerging genomic sequences of diverse bacteria indicate that these enzymes are present in virtually all Gram-negative organisms. An unanticipated genomic surprise, however, is that orthologs of key enzymes for lipid A biosynthesis are also present in higher plants. Lipid A (endotoxin) is the active component of LPS that stimulates immune cells. During severe Gram-negative infections, the lipid A moiety of LPS can cause excessive activation of macrophages and endothelial cells. The resulting systemic over-production of certain inflammatory mediators and clotting factors damages small blood vessels. A full response to endotoxin leads to Gram-negative septic shock with multiple organ failure and death. An exciting potential therapeutic approach to this problem has emerged with the discovery that certain lipid A-like molecules, including some precursors, are endotoxin antagonists. The primary signaling receptor for lipid A is now known to be the TLR4 protein, which is distantly related to the IL-1 receptor. In earlier work, the P. I. discovered the nine constitutive enzymes for lipid A assembly in E. coli, and the genes encoding them. In the proposed work, the specific aims are: I) elucidation of the biosynthesis of lipid A variants containing four amide-linked fatty acids; II) reengineering of the lipid A pathway in living E. coli cells; III) characterization of new PmrA and PhoP regulated enzymes that modify lipid A; IV) studies of cold shock and high Ca++ induced lipid A modifications in E coli: and V) analysis of lipid flip-flop and export in E. coli. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •

Project Title: BIOSYNTHESIS OF ENTEROBACTERIAL COMMON ANTIGEN Principal Investigator & Institution: Rick, Paul D.; Henry M. Jackson Fdn for the Adv Mil/Med Rockville, Md 20852 Timing: Fiscal Year 2001; Project Start 01-JUL-1984; Project End 31-MAR-2005 Summary: (Adapted from the Investigator's abstract): The long-term goals of this research are to gain a more complete understanding of the function of the outer membrane (OM) of gram-negative bacteria and the mechanisms involved in its biogenesis. As an approach to these goals, we have investigated the biochemistry and genetics of enterobacterial common antigen (ECA) synthesis and assembly in Escherichia coli. In addition, we have investigated the function of ECA in E. coli, Shigellaflexnerii, and Salmonella enterica serovar typhimurium. ECA is an OM glycolipid that is unique to the Enterobacteriaceae, and it is present in all members of this family. In spite of the ubiquitous occurrence of ECA in gram-negative enteric bacteria, the function of ECA has remained unknown. Our previous endeavors to study ECA synthesis and and assembly have been facilitated by the isolation and characterization of mutants defective in these processes. The characterization of these mutants has resulted in the identification of biosynthetic intermediates involved in ECA synthesis that have, in turn, led to the development of in vitro and in vivo experimental systems to demonstrate specific enzymatic steps in ECA assembly. Nevertheless, several important steps in the assembly of ECA remain to be established. We propose to

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continue this combined biochemical and genetic approach to complete the characterization of the assembly process. In addition, we have obtained exciting new data that strongly supports the conclusion that ECA plays an important role in the mechanism responsible for the resistance of gram-negative enteric bacteria to bile salts. Thus, the specific aims for the requested period of support are: (i) identification of the genetic determinant of ECA polysaccharide chain elongation in E. coil K-12, and biochemical characterization of the polymerization mechanism, (ii) determination of the role of o416 of the E. coli wec gene cluster in ECA assembly, (iii) isolation of E. coil mutants defective in the synthesis of the ECApG polysaccharide-aglycone linkage and biochemical characterization of the mechanism involved in linkage formation, and (iv) determination of the role of ECA in the resistance of gram-negative enteric bacteria to bile salts. It is anticipated that these studies will provide valuable insights into the assembly of other important membrane glycolipids and polysaccharides. Such information will also provide a rationale for the development of new antimicrobial agents. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •

Project Title: BIOSYNTHESIS OF MICROBIAL POLYKETIDES Principal Investigator & Institution: Cane, David E.; Vernon K. Krieble Professor of Chemistry; Chemistry; Brown University Providence, Ri 02912 Timing: Fiscal Year 2001; Project Start 01-AUG-1977; Project End 31-JUL-2005 Summary: Ongoing studies of the ensymology of complex polyketide natural product biosynthesis will be continued and extended, with focus on the macrolide antibiotics erythromycin (1), methymycin (2), and tylosin (3), as well as the antitumor metabolite epothilone (4). Each of these metabolites is assembled by exceptionably large, multifunctional, modular proteins known as polyketide synthases (PKSs) that are closely related to fatty acid synthases, both biochemically and genetically. In addition, epothilone synthase contains additional catalytic activities belonging to the class of nonribosomal peptide synthetases (NRPSs). A combination of chemical, enzymological, and molecular genetic techniques this being used to elucidate the molecular basis for the programming of the complex series of reactions responsible for polyketide chain elongation. The emphasis in this work is on the elucidation of the mechanisms of multistep, enzyme-catalyzed transformations leading to formation of biologically important metabolites. It is expected that the results of these studies will be broadly applicable not only to the understanding of polyketide and other natural product biosynthetic processes in general, but will provide fundamental insights into how catalysis and molecular recognition control both product specificity and molecular diversity in Nature. 1) Deoxyerythronolide B synthase (DEBS) is a modular PKS that catalyzes the formation of 6-deoxyerythronolide B (5), the parent aglycone of erythromycin A. Individual modules of the DEBS protein, responsible for catalysis of a single round of polyketide chain elongation and functional group modification, can be expressed in E. coli. These modules will be used to study the biochemical basis for the specificity and selectivity of individual catalytic domains, particularly the ketosynthase (KS) domains that mediate the key polyketide chain-building decarboxylative condensation reaction. 2) The methymycin and tylosin PKSs have intriguing similarities and differences to the well-studied DEBS system. Individual modules of the methymycin/picromycin and tylactone PKSs will be expressed in E. coli in order to investigate their biochemical function and substrate specificity. 3) The EpoA protein, the loading module for the epothilone hybrid PKS/NRPS, will be expressed in E. coli in order to study the EpoA-

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catalyzed conversion of malonyl-CoA to acetyl-S-EpoA, the substrate for the NRPS module EpoB. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •

Project Title: BIOTHREAT DETECTION WITH IMPROVED BACKGROUND REJECTION Principal Investigator & Institution: Kebabian, Paul L.; Aerodyne Research, Inc. the Research Ctr at Manning Park Billerica, Ma 01821 Timing: Fiscal Year 2003; Project Start 01-MAY-2003; Project End 31-OCT-2003 Summary: (provided by applicant): The Quartz Crystal Microbalance (QCM) is a wellestablished technology for quantifying small changes in mass. The long-term objective of this program is to improve the QCM so that it is suitable for use as a field test for the common, foodborne bacteria. To do this, we will modify the standard quartz crystal (QC) used in the QCM so as to increase its background rejection capabilities. This will involve innovations to the design of the QC used as the detector to the electronics. We will utilize standard technology to deposit a uniform coating of antibody directed against E. coli onto the surface of the QC. We will use utilize commercially available preparations of E. coli and Pseudomonas to demonstrate that the innovations introduced to the QC design and the electronics of the QCM allow a single QC to serve as both the experimental and the reference detectors. Thus, the modified QCM can discriminate between specific and non-specific binding of mass to the QC. We will use a second antibody, labeled with horseradish peroxidase to generate an insoluble reaction product to further amplify the mass of bacteria attached to the QC. Furthermore, we will utilize glutaraldehyde to non-selectively bind bovine serum albumin to antibody on the surface of both the conventional and modified QCs. Only the modified QC will be able to discriminate between specific binding of E. coli to the antibody and the non-specific cross-linking of BSA to antibody. We believe that our innovations will be of particular value in field tests in which there will be relatively small amounts of pathogenic agent and relatively large amounts of nonhazardous materials. In Phase II of the project, we will apply the technology developed in Phase I to the detection of other common foodborne bacterial contaminants. We will also extend our working relationship with academic laboratories to further test the device. We will work with diagnostics companies to determine their willingness to commercialize this technology. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen

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Project Title: CAMPYLOBACTER FETUS SURFACE LAYER PROTEIN SECRETION Principal Investigator & Institution: Thompson, Stuart A.; Assistant Professor; Biochem and Molecular Biology; Medical College of Georgia 1120 15Th St Augusta, Ga 30912 Timing: Fiscal Year 2001; Project Start 01-AUG-1998; Project End 31-JUL-2003 Summary: (Adapted from the applicant's abstract): Campylobacter fetus is a significant pathogen of cattle and immunocompromised humans. One of the major virulence factors of C. fetus is its surface layer (S-layer), which allows it to resist the bactericidal effects of normal and immune serum. Despite significant advances in understanding the molecular mechanisms of antigenic variation of surface layer proteins (SLPs, the subunits of the S-layer), until recently little was known about the secretion and assembly of SLPs. Preliminary data now reveal that C. fetus SLPs are transported by a type I secretion system [Sap(C)DEF] similar to those that recognize C-terminal secretion signals for the transport of toxins, proteases and lipases from gram-negative bacteria. This relationship is demonstrated by the inability of a C. fetus sapD mutant to produce

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or secrete SLPs, suggesting a possible link between the secretion and synthesis of SLPs. Furthermore, E. coli expressing C. fetus sapCDEF are able to specifically secrete a C. fetus SLP (SapA), verifying the sufficiency of these genes for SLP secretion. The ability of sapCDEF+ E. coli to secrete SLPs will be exploited for the delineation of the SapA Cterminal secretion signal. The investigators therefore propose the study of the mechanism of secretion of C. fetus SLPs as a necessary component of the process by which a major virulence factor of C. fetus is assembled, and as a model system for examining the interactions between heterologous type I transporters. They will do so in the following specific aims. Specific Aim #1. To characterize the components of the SLP secretion apparatus of C. fetus through the construction of additional mutations in the secretion apparatus. Studies on the potential regulation of sapA expression by intracellular SLPs will be performed to investigate a possible link between SLP synthesis and secretion. Specific Aim #2. To construct a C. fetus SLP secretion assay system using the cloned sapCDEF genes in E. coli. They will use deletion and mutational analyses to define the C. fetus SapA C-terminal secretion signal. The ability of the SapA secretion to mediate the transport of normally non-secreted proteins also will be assessed. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •

Project Title: CD-18 DEPENDENT/INDEPENDENT WBC RESPONSES IN THE LUNG Principal Investigator & Institution: Doerschuk, Claire M.; Professor of Pediatrics and Pathology; Pediatrics; Case Western Reserve University 10900 Euclid Ave Cleveland, Oh 44106 Timing: Fiscal Year 2003; Project Start 01-AUG-1994; Project End 31-MAY-2008 Summary: (provided by applicant): Neutrophil emigration into the lungs can occur through at least two different pathways depending upon the stimulus, one that requires the CD11/CD18 adhesion complex, and one that does not. Our studies provide evidence that mice deficient in the NF-kappaB p65 (Rel A) subunit, mice deficient in both TNF R1 and IL-1R1, or mice with blockade of ICAM-1 have defects in E. coli-induced CD18dependent emigration. In contrast, mice deficient in the leukocyte non-receptor Src tyrosine kinases Lyn, Fgr, and Hck, in the small GTPase Rac2, or in interferon-(IFN-g) have defects in S. pneumoniae-induced CD18-independent but not E. coli-induced CD18-dependent emigration. Moreover, exogenous IFN-( switches CD18-dependent to CD18-independent emigration, whereas genetic deficiency of IFN-( switches CD18independent to CD18-dependent emigration. Studies comparing gene expression during these bacterial pneumonias also provided many new ideas. Our goal is, to understand the mechanisms, through which CD18-dependent and CD18-independent adhesion pathways are elicited and function; and to identify ways of modulating the acute inflammatory process to benefit the host. Our working hypothesis is that neutrophil emigration occurs through CD11/CD18-dependent pathways when early stages of host defense result in nuclear translocation of NF-kappaB, production of TNF-alpha and IL-1, and increased expression of ICAM-1 on pulmonary capillary endothelial cells, while CD11/CD18- independent mechanisms are selected when IFN-( is produced and the leukocyte Src kinases Lyn, Fgr, and Hck and the small GTPase Rac2 are activated. The proposed Aims will test this hypothesis and examine the role of each of these required molecules in the mechanisms of neutrophil emigration. Aim 1 will determine the role of NF-(B -mediated gene transcription and the function of TNF-alpha and IL-1 in CD18dependent and -independent neutrophil emigration. Aim 2 will determine the role of IFN-g in CD18- independent emigration. Aim 3 will determine the role of Lyn, Fgr, and Hck and of Rac2, and the functional relationships between these molecules and IFN-g in

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neutrophil recruitment and function. Aim 4 will determine the functional role of molecules identified by gene microarray technology to be differentially expressed in S. pneumoniae but not E. coli pneumonia. These studies will help to elucidate the molecular mechanisms of neutrophil recruitment and identify potential targets for therapy. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •

Project Title: CHARACTERIZATION OF E.COLI F1FO-ATP SYNTHASE Principal Investigator & Institution: Senior, Alan E.; Professor; Biochemistry and Biophysics; University of Rochester Orpa - Rc Box 270140 Rochester, Ny 14627 Timing: Fiscal Year 2001; Project Start 01-SEP-1978; Project End 31-AUG-2005 Summary: Synthesis of ATP during oxidative phosphorylation occurs on the F1Fo-ATP synthase enzyme and accounts of the bulk of ATP synthesis in living cells. ATP synthase is an extraordinary enzyme because it acts as a molecular motor the energy of the transmembrane proton gradient is coupled through subunit rotation to the synthesis of ATP in three asymmetric but interconverting catalytic sites. In reverse, ATP hydrolysis drives subunit rotation and proton pumping. The long-term goal of this research is to understand the mechanism of F1Fo-ATP synthase in as much molecular detail as possible. The E. coli enzyme will be used because of its many advantages, e.g. it is readily amenable to molecular biology/genetic manipulations, it may be rapidly obtained in high yield, and it may be reconstituted in liposomes with excellent ATP synthesis activity. Specific goals are (1) determination of catalytic sites occupancy and nucleotide binding parameters in F1Fo in presence of a proton gradient, during ATP synthesis; (2) identification of functional interactions between gamma/alpha and gamma/beta subunits, by mutagenesis of residues in gamma which face alpha and beta; (3) elucidation of protein movements generated at the catalytic alpha/beta subunit interface as ATP hydrolysis proceeds through formation and collapse of the transition state to the ADP ground- state; (4) characterization of ATP hydrolysis at low ATP concentrations, where 120 degrees Celsius stepping of the rotor is seen; and (5) genetic analysis of the stator stalk, starting from mutations in alpha and delta subunits shown previously in this laboratory to interrupt both F1 binding to Fo and energy coupling. ATP-driven pumps are very widely distributed in nature, and are involved in many disease states. Work to be done here will consequently have broad impact in biology and medicine. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen

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Project Title: CHARACTERIZATION OF MYCOBACTERIAL AUTOLYSINS Principal Investigator & Institution: Deng, Lingyi; Medicine; Boston University Medical Campus 715 Albany St, 560 Boston, Ma 02118 Timing: Fiscal Year 2001; Project Start 01-AUG-1999; Project End 31-JUL-2002 Summary: (Adapted from the Applicant's Abstract): Mycobacterium tuberculosis remains the bacterial leading cause of death worldwide and multidrug-resistant strains have emerged as a new problem in both developed and developing countries. The cell wall of M. tuberculosis has a unique, complex structure and is extraordinarily thick, rigid, and hydrophobic. Because of these characteristics, it is highly impermeable to ordinary antimicrobial agents. Bacterial autolysins are enzymes which are capable of hydrolyzing the bacterial cell wall and are associated with normal bacterial cell division, growth, and autolysis. Little is known about the autolysins of mycobacteria. The central hypothesis of this proposal is that mycobacterial cell wall autolysins are essential for the

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growth and survival of the organisms and can be exploited as new targets for antimycobacterial agents. In preliminary studies, the investigators have (i) prepared a mycobacterial cell lysate that hydrolyzed the cell wall polysaccharide; (ii) observed that ethambutol treated mycobacteria have increased cell wall hydrolysis; and (iii) identified an open reading frame (ORF) in the M. tuberculosis genome that is highly homologous to a Bacillus subtilis cell wall hydrolases, i.e., an N-acetylmuranoyl-L-alanine amidase. The investigators now propose the following: AIM1. The putative M. tuberculosis amidase gene noted above will be amplified by PCR, cloned and expressed. If the protein is confirmed to have the predicted enzymatic activity, then its functional and biochemical characteristics will be determined and the expression properties of the gene will be analyzed. AIM 2. (a) Develop rapid and sensitive in situ phenotypic assays and apply these to screening for cloned mycobacterial autolysins expressed in E. coli. (b) Develop improved zymography and cell-free enzymatic assays and apply these to the isolation and purification of putative hydrolases. Purified enzymes will be analyzed for structural information (e.g. N-terminal sequence, quantitative protein mass as determined by MALDI/TOF mass spectroscopy), which will be used to identify the encoding gene in the published M. tuberculosis genome sequences. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •

Project Title: CONTROL OF DNA TOPOLOGY Principal Investigator & Institution: Tse-Dinh, Yuk-Ching; Associate Professor; Biochem and Molecular Biology; New York Medical College Valhalla, Ny 10595 Timing: Fiscal Year 2001; Project Start 01-APR-1996; Project End 31-MAR-2004 Summary: Due to the recent emergence of pathogenic bacteria resistant to all antibiotics currently used, there is an urgent lead to develop new antibiotics against novel targets. Bacterial topoisomerase I is a promising new target for antibacterial therapy with lead compounds having MIC's of 4.0 mug against Staphylococcus aureus. E. coli topoisomerase I is the best studied example of bacterial topoisomerase I and share extensive homology with topoisomerase I from both gram-positive and gram- negative bacteria. Topoisomerase I targeting drugs that inhibit DNA religation would lead to cell killing in a mechanism similar to those of many drugs targeting bacterial DNA gyrase and human topoisomerases. Loss of topoisomerase I function may also affect the ability of the bacteria to respond to environmental challenges encountered in pathogenesis. The long term goals of this project include the elucidation of the mechanism, regulation and physiological roles of E. coli topoisomerase I, which would greatly aid the development of novel bacterial agents targeting this class of enzyme. The aims for this proposal include: 1. Structure-function analysis by different mutagenesis approaches to identify residues required for the individual steps of catalysis by E. coli topoisomerase I 2. Limited proteolysis and chemical cleavage of topoisomerase I in the absence and presence of DNA to identify sites of cleavage altered due to either enzyme conformational change or protection by DNA substrate. 3. Test of peptide sequences identified by panning as potential inhibitor of topoisomerase I 4. Study of the molecular basis of topoisomerase I involvement in bacterial adaptation to environmental challenges for survival. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen

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Project Title: CORE--PROTEIN PRODUCTION Principal Investigator & Institution: Reinherz, Ellis L.; Chief; Dana-Farber Cancer Institute 44 Binney St Boston, Ma 02115

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Timing: Fiscal Year 2002; Project Start 01-AUG-2002; Project End 31-JUL-2007 Summary: This core will supply large-scale amounts of eukaryotic and prokaryotic expression system-produced proteins. Specifically, mini-proteins will be made in T7based E. coli expression systems as inclusion bodies. In addition, Lec3.2.8.1-generated ADA, 89.6P and clades C, A and O derivatives of HIV gp140, gp120 and gp140 miniproteins will be produced. As required, selenomethionine labeling of eukaryotically or E. coli expressed proteins will be undertaken for x-ray crystallography as well as 15N and 13C labeling of E. coli produced proteins for NMR analysis. Large-scale production of various mini-protein constructs will also be conducted. All monoclonal antibody generation, Fab antibody purification and crystallization trials will be established herein. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •

Project Title: CORE--X RAY CRYSTALLOGRAPHY Principal Investigator & Institution: Sundaramoorthy, Munirathinam; University of Kansas Medical Center Msn 1039 Kansas City, Ks 66160 Timing: Fiscal Year 2001; Project Start 30-SEP-2001; Project End 31-AUG-2006 Summary: The success of several sequence genomics projects heralds a new era in the study of the gene products and many of them are attractive targets for drug design. The new proteomics research uses multidisciplinary approach to study the "cellular protein universe" using several high-throughput methods. X-ray crystallography plays a pivotal role in both proteomics and structure based drug design. The University of Kansas Medical Center has envisioned a plan to establish "Kansas City Proteomics Initiative" and will set up an X-ray crystallography lab as a part of this plan in the Department of Biochemistry. This will serve as the Core facility for COBRE investigators who apply crystallography to their research. Funds are requested from COBRE for its maintenance. The Principal Investigator will direct the Core and his Research Project is summarized below. Gram-negative bacteria Neisseria meningitidis and Escherichia coli K1 are associated with sepsis and meningitis. There is no promising vaccine against N. Meningitidis group B and E. coli K1. Their capsular polysaccharides are sialylated, which are structurally similar to those found in mammalian glycolipids. This host mimicry plays and important role in the pathogenecity by allowing the bacteria to evade the host's immune system. Thus, sialic acid (N-acetylneuraminic acid, NeuNAc) is a virulence factor in these pathogenic bacteria. The biosynthesis of polysialic acid involves the formation and activation of NeuNAc. In bacteria, these two steps are catalyzed by NeuNAc synthase and CMP-NeuNAc synthetase, respectively. Our long-term goal is to study the structure-function relations of these enzymes using molecular biology, protein chemistry, and crystallography methods and use the structural knowledge of rational drug design. The specific aims of this application are: Aim 1: NeuNAc synthases from N. meningitidis and E. coli K1. In bacteria, sialic acid is synthesized by the condensation of N-acetylmannosamine with polyenolpyruvate by NeuNAc synthase. The human enzyme uses the phosphorylated substrates. The differences in the substrate specificity between human and bacterial enzymes may be due to different active site structures. Selective inhibition of bacterial enzyme is a viable strategy to prevent the synthesis of sialic acid in the pathogen. We will overexpress, purify, and crystallize NeuNAc synthases from N. meningitidis and E. coli K1 for structural-functions studies. Aim 2: CMP-NeuNAc synthetase from E. coli K1. The E coli K1 CMP-NeuNAc synthetase is twice as large as the other bacterial enzymes and about the same size as the mouse enzyme, the only mammalian CMP-NeuAc synthetase is sequenced. The N-terminal half of the E. coli K1 sequence is highly homologous to other bacterial sequences, but the

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full-length sequence share a limited homology with the mouse sequence. We will crystallize the E. coli K1 CMP-NeuAc synthetase for structure determination. The structural differences of these functional homologues will be used to design drugs to target the bacterial enzymes specifically. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •

Project Title: CRYSTALLOGRAPHIC STUDIES OF THYMIDYLATE SYNTHASE Principal Investigator & Institution: Finer-Moore, Janet S.; Research Biochemist and Biophysics; Biochemistry and Biophysics; University of California San Francisco 500 Parnassus Ave San Francisco, Ca 94122 Timing: Fiscal Year 2001; Project Start 01-DEC-1985; Project End 31-DEC-2003 Summary: The broad objectives of the work are to understand the functions of thymidylate synthase (TS) and other nucleotide, RNA and DNA-modifying enzymes. TS is an important drug target, since it provides the sole de novo pathway for synthesis of an essential DNA nucleotide. TS is the best characterized of the class of proteins that catalyze methyl transfer reactions in pyrimidine biosynthesis. Insights into the mechanism of TS have been applied to the study of related enzymes, such as the dUMP and dCMP hydroxymethylases, and DNA and RNA cytosine methyltransferases, and have deepened our understanding of general principles of catalysis of two-substrate reactions. The mechanism of TS will be investigated at a very detailed level by determining crystal structures of TS variants, generated by mutagenesis, in binary and ternary complexes with substrate, cofactor, or their analogs. Structures will be related to the results of kinetic and functional assays. A saturation mutagenesis approach will be used to define the roles of the approximately 25 conserved residues in the active site cavity. In this approach, a synthesized L. casei TS gene with strategically placed restriction sites is used to make all substitutions of the natural amino acids at a given site. Mutants of residues shown to have a role in the chemical steps following ternary complex formation will be made in E. coli TS for crystallographic study, since E. coli ternary complex crystal structures can be determined to ad least 2 Angstrom units resolution. Mutations which impair catalysis at different points in the multistep reaction will be used to isolate structures of new reaction intermediates by crystallography. The mechanism for hydride transfer in TS will be studied by determining the structure of SP01 dUMP-hydroxymethylase. This enzyme is structurally and mechanistically closely related to TS, but does not undergo the hydride transfer step. The enzyme will be crystallized and its structure determined by MIR methods. The crystal structure of tRNA pseudouridine synthase I, which modifies a uridine base in an E. coli tRNA, will be determined from already grown crystals that diffract to 1.35 Angstrom units resolution. MIR and MAD phasing techniques will be used to solve the structure. The protein will also be crystallized as a complex with a tRNA inhibitor. The mechanism of pseudouridine synthase will be investigated by mutagenesis of residues chosen based on the crystal structures. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen

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Project Title: DESIGN OF HEME PROTEIN BASED BLOOD SUBSTITUTES Principal Investigator & Institution: Olson, John S.; Professor; Biochemistry and Cell Biology; Rice University 6100 S Main Houston, Tx 77005 Timing: Fiscal Year 2001; Project Start 01-AUG-1991; Project End 31-MAR-2005 Summary: (Investigator's abstract) The long range goals are to develop O2 delivery pharmaceuticals based on extracellular recombinant hemoglobins (rHb). These next

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generation rHbs will be designed for optimal O2 transport, minimal interference with vasoregulation, enhanced resistance to denaturation, and increased expression levels in E. coli. Seven required properties are: (a) moderate O2 affinity (P50 5-30 mm Hg); (b) discrimination against CO binding; (C) large rate constants for oxygen binding and release; (d) significantly reduced rates of NO scavenging; (e) resistance to autooxidation and reactions with H2O2 (f) low rates of hemin dissociation; and (g) highly stable apoglobin structures. The mechanisms underlying these properties are being determined using sperm whale myoglobin as a simple prototype for the alpha and beta subunits of human hemoglobin, and the results are being used to develop strategies for solving specific problems in the clinical use and commercial development of extracellular hemoglobins (i.e., the hypertensive side effect and production costs). These mutagenesis studies will provide a database for evaluating more general principles for heme protein engineering. We will also address fundamental physiological questions about O2 transport and NO signaling and examine basic mechanisms of NO scavenging and O2 binding which apply to other key heme proteins, including flavohemoglobin NO dioxygenases. The specific aims for the next five years are to: (1) design new rHb products with low rates of NO scavenging and more efficient O2 transport properties to eliminate the hypertensive side effect of extracellular hemoglobin; (2) determine the relative importance of P50, oxygen dissociation rate constants, and cooperativity on O2 transport in capillaries in order to define the minimum requirements for efficacy; (3) examine systematically all physiologically relevant reactions of NO with the iron atom in hemoglobin to avoid other potential side effects; (4) improve the in vivo stability and in vitro shelf-life of recombinant hemoglobins by enhancing their resistance to autooxidation, reaction with H2O2, and heme loss; and (5) increase expression yields and lower cost of production in E. coli by enhancing the stability of apohemoglobin. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •

Project Title: DETECTION SALMONELLA

OF

MIXED

MICROBIAL

COMMUNITIES

BY

Principal Investigator & Institution: Ahmer, Brian M.; Assistant Professor; Microbiology; Ohio State University 1960 Kenny Road Columbus, Oh 43210 Timing: Fiscal Year 2001; Project Start 01-AUG-2001; Project End 31-MAY-2005 Summary: Despite decades of research on Escherichia coli and Salmonella typhimurium, microbiologists are still unable to assign, or even convincingly predict, functions for more than 30 percent of the open reading frames (ORFs) in the E. coli genome sequence. It seems likely that the functions of many of these genes may not be observable using pure cultures. In nature, such bacteria do not normally exist as pure cultures and a percentage of their genetic capacity is almost certainly involved with 'mixed community' interactions. Consistent with this hypothesis, we recently identified an S. typhimurium receptor that is activated only within a mixed microbial community. The signaling event discovered is the detection of N-acylhomoserine lactones (AHLs) by SdiA, a LuxR homolog found in S. typhimurium. The sdiA gene is also present in E. coli and Klebsiella spp, suggesting that it has a relatively ancient function. However, what is truly remarkable is that these species do not produce the ligands that are detected by SdiA. Instead, SdiA detects uncharacterized compounds present in mammalian intestines and AHLs produced by other species of bacteria. We will test the hypothesis that the intestinal compounds are microbial in origin and attempt to identify the species producing these molecules. We will use microarrays to identify the portions of the E. coli and S. typhimurium genomes that are regulated by SdiA in response to AHLs and characterize the phenotypic consequences of this signaling event.

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Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •

Project Title: DETOXICATION OF XENOBIOTICS IN ERYTHROCYTES Principal Investigator & Institution: Awasthi, Yogesh C.; Professor; Human Biol Chem and Genetics; University of Texas Medical Br Galveston 301 University Blvd Galveston, Tx 77555 Timing: Fiscal Year 2001; Project Start 01-JUL-1984; Project End 31-MAR-2004 Summary: (Adapted from the P.I.'s Abstract). In this revised competing renewal application, studies are proposed to characterize a novel xenobiotic/GSH-conjugate transporter, DNP-SG ATPase, present in human erythrocyte membranes. During the prior funding period the P.I. has demonstrated that: 1) Purified DNP-SG ATPase binds 8-azido ATP, catalyze ATP hydrolysis in the presence of an amphiphilic cationic drug, doxorubicin (DOX), as well as anionic GSH-conjugates. 2) It is distinct from the drug efflux pumps, P-glycoprotein (Pgp), and multi-drug resistance associated protein (MRP). 3) Purified DNP-SG ATPase reconstituted in proteoliposomes mediates ATPdependent, active transport of GSH-conjugates as well as DOX. 4) Using DNP-SG ATPase antibodies, the P.I. has cloned a cDNA from a human cDNA library which yields a recombinant protein (RLip 76) with properties similar to that of DNP-SG ATPase. The P.I. therefore hypothesizes that DNP-SG ATPase, which actively exports from the cell toxic xenobiotics and their metabolites, represents a major detoxication system for structurally diverse xenobiotics in normal cells. The P.I. plans to further characterize the DNP-SG ATPase/Rlip 76, and proposes three Specific Aims. In the first Specific Aim, the P.I. will obtain the recombinant RLip 76 protein from cDNA by heterologous expression in E. coli for use in structural and kinetic studies. The P.I. will transfect H-69 and K-562 cells with RLip 76 cDNA to examine whether the transfected cells are resistant to cytotoxicity mediated by xenobiotics/endobiotics which are substrates for this (RLip76) DNP-SG ATPase. In Specific Aim #2, the P.I. will functionally characterize the DNP-SG ATPase by reconstituting tissue-purified and recombinant (RLip76) DNP-SG ATPase in proteoliposomes to study the kinetics of transport of physiological anionic conjugates (e.g. leukotrienes, 4-HNE GSH conjugates of bilirubin), and drugs (e.g. DOX, daunomycin, etc.). In Specific Aim #3, the P.I. proposes to co-transfect RLip76 into H-69 and K-562 cells with the glutathione Stransferase (GST) isozyme, mGSTA4-4, to test the hypothesis that DNP-SG ATPase (RLip76) in conjunction with GSTs, plays a major role in the detoxication of endogenous and exogenous electrophiles in cells. These studies will provide clinically relevant information on the role of DNP-SG ATPase in cellular detoxication processes and on the mechanisms of multidrug resistance of cancer cells which do not express Pgp and/or MRP. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen

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Project Title: DNA REPAIR IN DRUG RESISTANCE MUTATION Principal Investigator & Institution: Rosenberg, Susan M.; Professor; Molecular and Human Genetics; Baylor College of Medicine 1 Baylor Plaza Houston, Tx 77030 Timing: Fiscal Year 2001; Project Start 01-JUL-1998; Project End 31-MAY-2003 Summary: Spontaneous mutation mechanisms are important in the origins and progression of cancer, development of resistance of tumors to chemotherapeutic drugs, resistance of pathogenic microbes to antibiotics, and other medically significant problems. This proposal focuses on understanding the molecular mechanism of a DNA repair protein-dependent mutation pathway that causes drug-resistance mutations in

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the chromosomes of enterobacteria. E. coli is use as a model organism. We have discovered that the RecA and RecBCD recombination-repair proteins of E. coli are necessary for the accumulation of beta-lactam drug-resistant mutations in the E. coli chromosome. This implicate either an SOS DNA damage repair-response, or recombinational DNA repair, or both, in the mutation mechanism. To our knowledge, this is only the third example known of mutagenesis dependent on RecA and RecBCD. The first is from work on stationary-phase ("adaptive") reversion of an episomal lac frameshift mutation in E. coli. Significant insights into the molecular mechanism of stationary-phase mutation in the lac system have been obtained. These provide unique and powerful entry into understanding the molecular mechanism of these chromosomal mutations, which will be exploited by the work proposed here, usin the well developed genetics of the E. coli model system. The goal of this project is to provide a complete description of the molecular mechanism of DNA repair-gene dependent chromosomal mutation to drug-resistance. The principles learned in this new model system may apply to chemotherapeutic drug-resistance to other antibiotic resistances, and to other mutations that may be caused or facilitated by mutational and DNA repair-related events during drug exposure. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •

Project Title: DNA REPLICATION IN BACILLUS SUBTILIS Principal Investigator & Institution: Mchenry, Charles S.; Professor; Biochem & Molecular Genetics; University of Colorado Hlth Sciences Ctr P.O. Box 6508, Grants and Contracts Aurora, Co 800450508 Timing: Fiscal Year 2003; Project Start 01-AUG-2003; Project End 31-JUL-2007 Summary: (provided by applicant): Decades of study have provided us with detailed information about DNA replication in E.coli. The explosion of bacterial genomic sequences has enabled facile exploration beyond the standard E. coil prototype. The objective of these proposed studies is to establish a complete replication system for a second very distant bacterium, B. subtilis. B. subtilis is ideally suited for these purposes because i. it is diverse, belonging to the low GC Gram (+) classification, evolutionarily distant (>>1 billion yr.) from Proteobacteria and E. coli, ii. its genome has been sequenced and it has a developed genetic system, iii. it can be grown in fermentors in large quantity making it suitable for biochemical analysis, iv) genomics indicates it is representative of the most diverse group of bacteria from a DNA replication standpoint (having two apparent distinct replicases and a number of replication proteins with no counterpart in E. coli, and v) it provides a model system representative of an important group of important human pathogens (streptococci, staphylococci and enterococci. The studies for the proposed grant period build upon a strong base established through unfunded preliminary studies and will focus upon establishing i. the identity of the elongation apparatus components and function, ii. the proteins required for providing RNA primers and iii. the proteins required for origin-specific initiation. Emphasis will be placed on those features of the B. subtilis replication system that make it distinct from E. coli. This will provide important information regarding the variations that can be expected between bacterial replication systems in terms of basic components, mechanisms and regulation. Understanding the biochemical details of DNA replication in an organism that contains two DNA polymerase Ills, may provide paradigms applicable to other two-polymerase replicases including eukaryotes where Pol epsilon and delta both appear to be involved in processive chromosomal replication. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen

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Project Title: DRUG DESIGN FOR TREATING OPPORTUNISTIC INFECTION IN AIDS Principal Investigator & Institution: Krause, Kurt L.; Associate Professor; Biology and Biochemistry; University of Houston 4800 Calhoun Rd Houston, Tx 77004 Timing: Fiscal Year 2001; Project Start 30-SEP-1999; Project End 31-AUG-2004 Summary: Mortality in AIDS patients is due to overwhelming opportunistic infections caused by bacteria, fungi, protozoa, and viruses. The long term goal of this project is to develop lead compounds useful for the treatment of bacterial opportunistic infections in AIDS by developing strong inhibitors of alanine racemase, an essential bacterial enzyme involved in cell wall biosynthesis. These compounds will be engineered in a collaborative structure based drug design program based at the University of Houston. Three common opportunistic pathogens will be targeted, Mycobacterium tuberculosis, Mycobacterium avium, and Streptococcus pneumoniae, but several other pathogens will be studied as well. To date, overexpressing clones of alanine racemase from E. coli, Mycobacterium tuberculosis, Pseudomonas aeruginosa, Staphylococcus aureus, and Streptococcus pneumoniae have been used to produce purified protein. These enzymes are being characterized kinetically. Crystallization of all of these racemases will be attempted, and alanine racemase from E. coli, Pseudomonas aeruginosa and Mycobacterium tuberculosis have already been crystallized. The crystals from the E. coli enzyme are of sufficient quality to allow for a three-dimensional structure determination. These structures will serve as target molecules for a comprehensive structure based drug design effort. Promising lead compounds will be synthesized and tested in vitro. Their strength and specificity will be improved through structural determinations of inhibitor-enzyme complexes followed by molecular dynamics simulations. Studies of mutant racemases will be used to help anticipate common pathways for developing resistance to these compounds. While the treatment of opportunistic infections in AIDS patients will benefit most from this research, development of highly effective alanine racemase inhibitors may broadly impact the treatment of other infectious diseases, including those caused by multi-drug resistant bacteria. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen

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Project Title: E COLI INVASION OF BRAIN ENDOTHELIAL CELLS Principal Investigator & Institution: Kim, Kwang S.; Professor and Director; Pediatrics; Johns Hopkins University 3400 N Charles St Baltimore, Md 21218 Timing: Fiscal Year 2001; Project Start 01-MAR-1988; Project End 31-AUG-2004 Summary: Description (Adapted from the applicant's abstract): The mortality and morbidity associated with neonatal bacterial meningitis have remained significant despite advances in antimicrobial chemotherapy and supportive care. Inadequate knowledge of the pathogenesis and pathophysiology has contributed to this high mortality and morbidity. E. coli is the most common gram-negative organism that causes meningitis during the neonatal period. Most cases of E. coli meningitis in newborns develop as a result of hematogenous spread, but it is not clear how circulating E. coli cross the blood-brain barrier. We have established an infant rat model of experimental hematogenous meningitis which mimics human E. coli meningitis (e.g. hematogenous infection of meninges). We have also established an in vitro model of the blood-brain barrier with brain microvascular endothelial cells (BMEC). Using these in vitro and in vivo systems, we have shown that invasion of BMEC is a requirement for E. coli K1 crossing of the blood-brain barrier in vivo. During the previous funding period,

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we have shown that several E. coli K1 determinants contribute to invasion of BMEC in vitro and crossing of the blood-brain barrier in vivo (i.e., OmpA, IbeA, IbeB, IbeC, CNF1). We also showed that E. coli K1 invasion of endothelial cells is specific to BMEC, and no such invasion was observed for endothelial cells of non-brain origin. We have so far shown that some of the E. coli proteins (e.g., OmpA, IbeA) interact with specific receptors present on BMEC, not on systemic vascular endothelial cells. In addition, we showed that actin cytoskeleton rearrangements are involved in E. coli K1 invasion of BMEC, as shown by invasive E. coli K1-associated F-actin condensation and blockade of invasion by cytochalasin D. Based on the resources and findings derived from the past funding period, we would like to examine the following specific aims. 1. To continue to identify and characterize microbial determinants contributing to E. coli K1 invasion of BMEC in vitro and in vivo 2. To examine the mechanisms involved in E. coli K1 invasion of BMEC, including structure-function analysis of E. coli proteins, and identification and characterization of BMEC receptors. 3. To determine host cell signal transduction pathways involved in E. coli K1 invasion of BMEC, including focal adhesion kinase (FAK), Rho and phosphatidylinositol (PI)3-kinase. Further understanding and characterization of these E. coli K1-BMEC interactions should allow us to develop novel strategies to prevent this serious infection. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •

Project Title: E COLI SSB PROTEIN/DNA INTERACTIONS Principal Investigator & Institution: Lohman, Timothy M.; Professor; Biochem & Molecular Biophysics; Washington University Lindell and Skinker Blvd St. Louis, Mo 63130 Timing: Fiscal Year 2001; Project Start 01-JUL-1990; Project End 31-MAR-2003 Summary: The proposed research is to obtain a molecular understanding of the interactions of the E. coli Single Stranded DNA Binding (SSB) protein with single stranded (ss) DNA using thermodynamic, kinetic and structural approaches. The SSB protein is a helix destabilizing protein that binds selectively and cooperatively to sspolynucleotides and is essential DNA replication and repair and facilitates homologous recombination in E. coli. It is a homo-tetramer and serves as a paradigm for a growing number of similar tetrameric SSB proteins from other organisms, including human mitochondria. The protein displays a complex array of ss-DNA binding features, including multiple DNA binding modes, multiple inter-tetramer positive cooperativities, and dramatic negative cooperativity for ss-DNA binding within an individual tetramer. There is evidence suggesting that the different SSB-sspolynucleotide binding modes and cooperativities may be used selectively in different functions in vivo and that the transition between these modes is regulated by the negative cooperativity. We are interested in the SSB protein since it is an essential DNA replication protein and a paradigm for the class of SSB proteins. However, we also study it to probe the fundamental thermodynamic linkages that occur in protein-DNA interactions and as a model for studies of negative cooperativity in protein-ligand systems. Detailed thermodynamic studies over a range of solution conditions are essential to obtain an understanding of the functional energetics of protein-DNA interactions. A particular emphasis of our studies is to probe the thermodynamic effects of salt concentration and its linkage to other variable, since electrostatic effects are dominant in protein-nucleic acid systems. The proposed studies focus on SSBoligodeoxynucleotide interactions since these allow more precise determinations of the thermodynamics of binding and negative cooperativity. The thermodynamics of oligodeoxynucleotide binding will be examined by two approaches: (1) equilibrium

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E. coli

binding parameters (binding and negative cooperativity constants) will be obtained as a function of solution conditions (pH, temperature, salt concentration and type) from analyses of equilibrium isotherms obtained by fluorescence techniques and (2) isothermal titration calorimetry. Kinetic and mechanistic studies will be performed using fluorescence stopped-flow techniques. We will also initiate a new project to examine the ability of the SSB protein to destabilize intramolecular hairpins that can form within ss-DNA during replication and in transiently melted regions of duplex DNA. We are also collaborating wit Dr. Gabriel Waksman to obtain atomic level structural information through X-ray crystallographic analysis of co-crystals of SSB-ssoligodeoxynucleotide complexes that we have recently obtained. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •

Project Title: E. COLI BASED VECTORS FOR GENE DELIVERY TO HUMAN CELLS Principal Investigator & Institution: Warburton, Peter E.; Assistant Professor Human Genetics; Human Genetics; Mount Sinai School of Medicine of Nyu of New York University New York, Ny 10029 Timing: Fiscal Year 2001; Project Start 15-FEB-2001; Project End 31-DEC-2002 Summary: (applicant's description) The overall objective of this proposal is to develop an E. coli based vector system for the functional delivery of large genomic transgenes into human cells. Gene therapy holds great promise for the biomedical sciences in the treatment of genetic disease and cancer. Initial results with viral and liposome-based vector systems have been encouraging, but are limited by the relatively short length of DNA that can be delivered, with resultant variable levels and duration of gene expression. Delivering large genomic DNA-based transgenes, with sufficient surrounding genomic sequences to include not only the gene of interest but also endogenous promoters, introns and essential cis-acting elements, will display more accurate spatio-temporal expression compared to cDNA constructs. The efforts of the Human Genome Project have made large sequenced BAC and PAC clones containing human genes and surrounding genomic DNA readily available. However, lack of a suitable delivery method has hindered gene therapy studies using these valuable resources. Thus, the following three specific aims are designed to develop novel E. coli based gene therapy vectors capable of delivering large genomic clones. 1) An inducible homologous recombination system will be adapted to the E. coli DH10B to permit engineering of BACs. E. coli strain DH10B is recombination deficient (RecA-), making it the preferred vector for stably cloning large intact human genomic DNA into BACs. Providing several recombination proteins under control of an arabinose-depending promoter results in an inducible homologous recombination system. 2) E. coli DH10B will be made competent to invade mammalian cells and deliver large BACs, by expressing the Versinia pseudotuberculosis invasin gene and creating a deficiency in cell wall synthesis (dapA). 3)Human functional centromere DNA sequences will be engineered onto these BACs to provide mitotic stability to the transferred DNA in dividing cells. The human centromeric alpha satellite DNA has been shown to form de novo centromeres when introduced into human cells, creating human artificial chromosomes (HACs). However, these first generation HACs consist of greatly rearranged DNA, making them of limited use as gene expression vectors. The ability to engineer large BACs to contain human centromeric DNA and introduce then into human cells as HACs will overcome many of the limitations of previous HAC vectors. These studies propose to develop E. coli-based HAC vectors for human gene therapy

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that encompass novel approaches for gene delivery, accurate gene expression, and mitotic stability. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •

Project Title: EFFECT OF MUCOSAL BARRIER ON SHIGA TOXIN ABSORPTION Principal Investigator & Institution: Morgan, Timothy W.; Veterinary Pathology; Iowa State University of Science & Tech Ames, Ia 500112207 Timing: Fiscal Year 2001; Project Start 01-APR-2001; Project End 31-MAR-2004 Summary: (provided by applicant): Diarrheal diseases caused by enteropathogenic Gram-negative bacteria are a risk factor for morbidity and mortality in people who live in both underdeveloped and developed countries including the United States. E. coli 0157:H7 has increasingly been recognized as a cause of hemorrhagic colitis and the associated complicating condition, hemolytic uremic syndrome. E. coli 0157:H7 colonizes the intestine, intimately attaches to the intestinal mucosa in a process that requires intimin (an adhesion factor), induces hemorrhage and acute inflammation, and releases Shiga toxins (Stx) that are absorbed systemically and cause vascular damage. The process by which Stx enters the systemic circulation is poorly understood. Studies in rabbits and our preliminary data suggest that reduction of leukocyte (i.e. neutrophil) adherence by adhesion molecule inhibitors reduces the clinical severity of disease and reduces death caused by E. coli 0157:H7. It is our hypothesis that damage to the intestinal mucosa enhances passive absorption and systemic spread of Stx, resulting in enhanced Stx-induced lesions in brain and blood vessels. This damage may be caused by the bacteria, the host inflammatory response, or a combination of the two. A 3-day old pig model of E. coli 0157:H7 enteritis produced by a wild type (Stx positive, intimin positive strain) will be developed. This model will be used to determine if infection by an intimin positive, Stx negative strain of E. coli 0157:H7 or if chemically induced mucosal ulceration enhance absorption of exogenous Stx. In each of these studies, one group of pigs will be treated with a selectin inhibitor, TBC 1269, to reduce neutrophil infiltration and the results wilt be compared to the non-treated control groups to determine the contribution of neutrophils to mucosal damage and Stx absorption in a 3day old pig model of E. coli 0157:H7 enteritis. The results of these studies will help define the mechanistic basis of Stx absorption, potentially leading to new therapeutic approaches to treating E. coli 0157:H7 enteritis and the associated systemic lesions. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen

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Project Title: ENTEROHEMORRHAGIC E COLI ALTER INTESTINAL FUNCTION Principal Investigator & Institution: Hecht, Gail A.; Professor of Medicine; Medicine; University of Illinois at Chicago 1737 West Polk Street Chicago, Il 60612 Timing: Fiscal Year 2001; Project Start 30-SEP-2000; Project End 31-JUL-2005 Summary: Infection with enterohemorrhagic E. coli (EHEC), acquired from contaminated food or water, represents a major health problem worldwide with EHEC being the fourth most costly foodborne pathogen in the USA. Although many EHEC strains produce Shiga toxin (Stx), its role in pathogenesis is not understood. In some species, the presence of attaching and effacing (A/E) lesions correlate more closely with intestinal symptoms than does the expression of Stx. While the formation of A/E lesions may be sufficient to induce diarrhea, the production of Stx may be a prerequisite for hemorrhagic colitis. These findings underscore the lack of understanding of the pathogenesis of EHEC. While much effort has been focused on the extraintestinal manifestations of EHEC, the effects of this important pathogen on the intestine have

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been grossly understudied. The hypothesis of this proposal is that EHEC has direct effects on its initial host target tissue, the intestinal epithelium, which contribute to the associated symptoms. The studies proposed here will utilize two separate models to investigate the effects of EHEC infection on intestinal epithelial function, a reductionist model of cultured human intestinal epithelia and a murine model. Preliminary data show that two major physiological processes, tight junction (TJ) barrier function and the epithelial-initiated inflammatory cascade, are altered in both of these models following infection with EHEC. It is likely that both of these alterations contribute to EHECassociated diarrhea. The impact of EHEC infection on these physiological functions and the underlying mechanisms will be explored by three Specific Aims. The first Specific Aim is to characterize the effect of EHEC on intestinal epithelial tight junction barrier function. The mechanisms by which EHEC perturbs the TJ barrier will be addressed focusing on the role of cytoskeletal contraction and changes in key TJ-associated proteins. Specific Aim 2 is to define the signaling pathways by which EHEC activates the inflammatory response within intestinal epithelial cells. The events that lead to the activation of NF-kappaB, the upregulation of pro- inflammatory cytokines, such as IL-8, and neutrophil transmigration will be explored. The studies outlined in Specific Aims l and 2 will use the established in vitro cell culture model. Specific Aim 3 is to establish and characterize a murine model of intestinal EHEC infection, The effects of EHEC infection on TJ barrier function as well as epithelial-initiated inflammation will be explored. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •

Project Title: ENZYMATIC REACTION MECHANISMS Principal Investigator & Institution: Walsh, Christopher T.; Assistant Professor; Biological Chem & Molecular Pharm; Harvard University (Medical School) Medical School Campus Boston, Ma 02115 Timing: Fiscal Year 2001; Project Start 30-SEP-1987; Project End 31-DEC-2003 Summary: The goals of this proposal are the study of enzymatic reaction mechanisms. In this project period the focus is on the reaction mechanisms of two kinds of enzyme systems involved in the biosynthesis of peptide antibiotics. The first is the enzymatic heterocyclization machinery involved in the conversion of the 69aa Microcin A protein, an antibiotic precursor, to Microcin B17, an antibiotic targetted against E.coli DNA gyrase, in which 14 residues (six gly, four ser, four cys) have been posttranslationally modified to four thiazole and four oxazole rings, essential for antibiotic activity. The second goal is analysis of the enzymatic strategies used by multimodular enzymes that make peptide bonds nonribosomally, e.g. in the biosynthesis of peptide antibiotics and iron-chelatina siderophores. The example to be studied is the four enzyme system, Ent B,D,E,F, responsible for formation of the E. coli iron chelator enterobactin. In particular the EntF enzyme has four domains (Condensation, adenylation, peptidyl carrier protein and thioesterase) whose functions in assembly of the (dihydroxybenzoyl)-serine trilactone, enterobactin, will be analyzed in terms of covalent priming, initiation, elongation, and termination strategies. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen

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Project Title: ENZYME MEDIATED THIOL MODIFICATION OF TRNA Principal Investigator & Institution: Lauhon, Charles T.; None; University of Wisconsin Madison 750 University Ave Madison, Wi 53706 Timing: Fiscal Year 2001; Project Start 01-JAN-1998; Project End 31-DEC-2002

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Summary: Base modification in tRNA represents the find tuning of a crucial process in cellular metabolism - the faithful translation of messenger RNA into protein. The modification enzymes are unique in that their substrates are highly structured tRNA molecules; thus, they provide an opportunity to study protein-RNA interactions in the context of mechanistic enzymology. The long range goal of this work is to understand the enzymatic mechanisms of thiol modification at two specific sites in E. coli tRNA, uridine 8 (U8) and adenosine 37 (A37), that are implicated in regulatory events in bacterial metabolism. In addition, these enzymes will be used to explore RNA-protein interactions in an effort to understand the basis for their observed specificity at the nucleotide level. The specific aims of the proposed work are as follows: (1) Enzyme assays will be developed to allow the purification of the modification enzymes. The enzymes will be purified to homogeneity, using affinity chromatography of immobilized RNA fragments derived from substrate specificity studies. The structural genes will be cloned from E. coli using sequence information from the purified proteins. (2) the mechanism will be investigated by which sulfur is transferred to the tRNA bases, in each case from cysteine via different cofactors and presumably different mechanisms. (3) The role of iron dependence in the thiolation of A37 will be explored through the development of specific inhibitors of this step and observation of the metabolic effects of such inhibition as compared to previously described genetic mutants. (4) The tRNA substrate specificity of the enzymes will be elucidated using in vitro selection techniques that explore the primary, secondary and tertiary structure determinants for activity as a substrate. The thiol modifications will be used as chemical tags to retrieve active molecules from mutagenized libraries of E. coli tRNAPhe. Specific relevance to medical issues lies in the fact that the A37 modification is thought to act as a sensor in bacteria for conditions of low iron availability. Such conditions arise in host (e.g., mammalian) fluids inhabited by enteric pathogenic bacteria. In addition, the knowledge gained from this work is directly relevant to the current study of molecular recognition events between RNA and proteins, such as retroviral assembly and RNA processing and transport, that are involved in many disease related processes. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •

Project Title: ENZYMES IN THE CRYSTALLINE STATE Principal Investigator & Institution: Ludwig, Martha L.; Professor; Biological Chemistry; University of Michigan at Ann Arbor 3003 South State, Room 1040 Ann Arbor, Mi 481091274 Timing: Fiscal Year 2001; Project Start 01-SEP-1977; Project End 31-MAR-2004 Summary: (Verbatim from the applicant's abstract) The long-term goal is to relate molecular structure to specificity and reactivity in enzymes, with high-resolution x-ray structure analysis as a primary method. This proposal focuses on local and global conformational changes that are essential in catalysis and control, using enzymes that provide paradigms for domain 'motions', for transition state stabilization, and for interactions mediated through proteins by structural changes. Some of the selected enzymes are dependent on metallo- or vitamin-based cofactors. Genetic engineering, spectroscopic, and biochemical techniques will also be deployed to show how the function of each protein depends on conformational equilibria. Descriptions of domain rearrangements will be obtained for two prototypical enzymes: B12-dependent methionine synthase (MetH) and the flavoenzyme, thioredoxin reductase (TrxR). MetH from E. coli is a modular 136 kDa protein with regions that bind homocysteine, methyltetrahydrofolate, B12, and adenosylmethionine (AdoMet). MetH operates by an alternating domain scheme that requires different modules to interact in turn with the

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E. coli

B12 domain. Structure-function analyses will define the arrangements and interactions of modules in the catalytic and reactivation states, and will help to explain how conversions between conformations are triggered. Impairment of human methionine synthase, an analog of the E. coli enzyme, is responsible for many of the manifestations of B12 deficiency. TrxR, a two-domain protein, employs domain rotations to present NADPH and the active site disulfide alternately to the FAD cofactor. These rotations limit the rate of catalysis. One of the reactive conformations has been described by Kuriyan and coworkers. The other conformer will be analyzed, stabilizing it via -S-Slinks to the substrate, thioredoxin. Conformation changes that occur in catalytic cycles or modulate activity in cytidylyltransferases and methylenetetrahydrofolate reductase (MTHFR) will be established from structures of substrate, product and intermediate complexes. Initial analyses of glycerol-3-phosphate:cytidylyltransferase have revealed local conformational changes linked to substrate binding, and imply interactions between the active sites of the dimeric molecule. Structures of intermediates, including a transition state mimic, will be determined. E. coli MTHFR is a bacterial model for investigation of the role of this enzyme in controlling levels of homocysteine, a known risk factor for cardiovascular disease. Objectives are analyses of structures of wild type and mutant enzymes with folates bound, and the crystallization of human MTHFR, which displays allosteric control by AdoMet. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •

Project Title: FUNCTIONAL ANALYSIS OF AN RNA STRUCTURAL MOTIF Principal Investigator & Institution: Hou, Ya-Ming; Associate Professor; Biochem & Molecular Pharmacol; Thomas Jefferson University Office of Research Administration Philadelphia, Pa 191075587 Timing: Fiscal Year 2001; Project Start 01-AUG-1998; Project End 31-JUL-2002 Summary: (Adapted from Applicant's Abstract) Although various aspects of transfer RNA (tRNA) recognition by aminoacryl-tRNA synthetases have been well established, that of structural recognition is not understood. The study of recognition of E. coli tRNACys by cysteine-tRNA synthetase offers the potential that questions of tRNA structural recognition can be addressed. One objective is to determine the mechanism of contribution of a single nucleotide U73 to aminoacylation. A second objective is to investigate the scope and impact of a structural recognition of an unusual G15:G48 base pair that is unique to E. coli tRNACys. A third objective is to study the potentially novel mechanism of aminoacylation with cysteine in an archaebacterium. In aim 1, the hypothesis that U73 uses its functional groups to contribute to aminoacylation will be tested. In aim 2, the hypothesis that U73 uses its ability to confer a fold-back structure of the CCA end to contribute to aminoacylation will be tested. In aim 3, the biologically relevant structure of the important G15:G48 in E. coli tRNACys will be defined and tested, In aim 4, the hypothesis that G15:G48 coordinates with multiple nucleotides to contribute to aminoacylation will be tested. In aim 5, the hypothesis that tRNA structural recognition is the primary difference between the E. coli and human systems of aminoacylation with cysteine will be tested. In aim 6, the hypothesis that aminoacylation of tRNACys in the archaebacterium Halobacter volcanii (H. volcanni) is catalyzed by a novel cysteine-tRNA synthetase will be tested. The results of these studies will be integrated into structural studies of tRNACys and its complex with cysteine-tRNA synthetase in order to have a better understanding of tRNA structural recognition by an aminoacyl-tRNA synthetase. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen

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Project Title: GENE EXPRESSION PATTERNS BY URINARY TRACT PATHOGENS Principal Investigator & Institution: Lory, Stephen; Professor; University of Washington Seattle, Wa 98195 Timing: Fiscal Year 2001; Project Start 01-FEB-2001; Project End 31-JAN-2002 Summary: The ability of pathogenic bacteria to sense the changes in their environment and respond by expressing essential virulence is one of the key components of the infectious process. The long term objectives of the proposal are to examine the patterns of gene expression of two important human uropathogens-Escherichia coli and Pseudomonas aeruginosa-during various growth conditions, including growth in the urinary tract of infected patients. Specifically, a library will be prepared of cloned DNA from a uropathogenic E. coli strain containing sequences which are absent in the genomes of laboratory E. coli strains. Similarly, a genomic library of uropathogenic P. aeruginosa strain will be constructed. These libraries will be used to prepare filters containing high-density DNA arrays of clones, and they will be probed with cDNA probes derived from mRNAs isolated under various conditions that mimic the human urinary tract. Two such conditions will include growth in human urine, and bacterial attachment to human bladder epithelial cells in culture. In order to identify genes that are differentially expressed, the hybridization patterns of two different probes with the cloned DNA in arrays will be compared. RNA will be isolated from the pathogens propagated in urine or in the presence of primary bladder epithelial cells, and the same organisms grown in standard laboratory media. Probes from E. coli and P. aeruginosa, directly isolated in urine samples from patients with urinary tract infections will also be prepared, and these will be used for the analysis of gene expression during natural infections of humans. Genes of E. coli and P. aeruginosa, which are expressed in isolates from patients with urinary tract infections-or under conditions mimicking such infections-will be cloned and sequenced. The transcriptional start sites of these genes will be determined, in order to identify any urine-tract specific regulatory genes, which may be targets of transcriptional regulators. It is believed that the proposed research will lead to the identification of genes and regulatory circuits which are responsible for the expression of virulence factors in the human urinary tract infected by uropathogenic E. coli and P. aeruginosa. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen

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Project Title: GENE POLYMORPHISMS PREDISPOSING TO INFECTIOUS DIARRHEA Principal Investigator & Institution: Okhuysen, Pablo C.; Associate Professor; Internal Medicine; University of Texas Hlth Sci Ctr Houston Box 20036 Houston, Tx 77225 Timing: Fiscal Year 2003; Project Start 30-SEP-2003; Project End 31-DEC-2007 Summary: (provided by applicant): After exposure to an enteropathogen, the manifestations of infectious diarrhea are variable and depend on host and pathogen factors. A variety of host factors modulate the likelihood of infection or severity of symptoms and can be categorized as those that mediate susceptibility (i.e., host genetic factors, pathogen receptors), and injury (i.e., stimulation of fluid and electrolyte channels, pro inflammatory cytokines). Resolution of infection is determined by factors that contribute to the phases of control and healing (i.e., anti-inflammatory cytokines and specific immunity). Our central hypothesis is that genetic polymorphisms that lead to qualitative or quantitative differences in one or several of these mediators are partially responsible for the development of infection and illness after exposure to enteric pathogens. To this end we will study two well-characterized populations of

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E. coli

subjects with infectious diarrhea. The first study group will consist of healthy adults traveling from developed nations to areas of risk for infection with bacterial agents of diarrhea. The second study group will consist of healthy adults experimentally exposed to Cryptosporidium at the University of Texas - Houston Clinical Research Center. For both we propose to investigate host single nucleotide polymorphisms (SNPs) of genes that encode proteins that are associated with either susceptibility, modulation of disease manifestation (injury), eradication (Control) and healing after infection. We will focus on three agents with potential for bioterrorism use by waterborne or food borne routes with distinct pathophysiology; enterotoxigenic E. coli a cause of secretory diarrhea, Enteroaggregative E. coli, a cause of inflammatory diarrhea and Cryptosporidium an intracellular pathogen. SNPs will be correlated with the isolation of an enteropathogen and clinical illness. The impact of SNPs will be examined in the context of different ethnic backgrounds. The understanding of the outcome of infection as they relate to host genetic factors will be of use in designing biodefense interventions that are directed towards improving risk assessment. The identification of populations that are more susceptible or vulnerable to the effects of enteric pathogens will be important in the design of strategies to decrease the impact that these agents may have in causing disease and defining the populations most likely to benefit from prevention, treatment and or vaccines. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •

Project Title: GENE ENVIRONMENT

REGULATION

E.COLI

DATABASE

INTERGRATED

Principal Investigator & Institution: Collado-Vides, Julio; National Autonomous University of Mexico Po Box 70-228, D.F. 4510 Mexico City, Timing: Fiscal Year 2001; Project Start 17-SEP-2001; Project End 31-AUG-2004 Summary: (provided by applicant): The purpose of this application is to implement an integrated computational environment around a database on transcriptional regulation in E. coli. This database, RegulonDB, contains information gathered from the literature on regulatory elements and operon organization, their location in the genome, and experimental evidence supported by more than 1000 Medline original literature references. The project would transform the database into a useful tool for analysis of transcriptome and proteome experiments. Aim 1 is to gather data on growth conditions and their associated signal metabolites, and to expand the graphic capabilities of the system. Aim 2 consists in implementing and coupling the database with tools for genomic regulatory analyses, such as sequence retrieval, pattern discovery and pattern search, as well as a syntactic recognizer to detect multiple potential regulatory elements within an upstream region. Aim 3 centers on programs which would use as input a set of genes from a transcriptome experiment, and generate graphical or tabular information about their operon organization, upstream regulatory sites, functional classes of genes, and regulators affected. All these tools would integrate a flexible navigation path where the output of one query is the input for another one. Aim 4 consists in expanding and applying a Bayesian clustering method designed to deal with the heterogeneous type of information of gene regulation and metabolism. E. coli is here the model system, however, this approach and tools can in principle be applied to the study of other microbial organisms, resulting in more efficient ways to make use of currently available massive amounts of knowledge for the purpose of a better understanding of their biology, and potentially of their mechanisms affecting human health. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen

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Project Title: INFECTIONS

GENOMICS

OF

SUSCEPTIBILITY

TO

URINARY

31

TRACT

Principal Investigator & Institution: Hopkins, Walter J.; Senior Research Scientist; Surgery; University of Wisconsin Madison 750 University Ave Madison, Wi 53706 Timing: Fiscal Year 2003; Project Start 01-AUG-2003; Project End 31-MAY-2008 Summary: (provided by applicant): Recurrent urinary tract infections (RUTI) in adult women are a significant source of patient morbidity and can lead to long-term kidney damage in some cases. Ongoing research is directed towards identifying host factors that contribute to increased susceptibility; however, as yet there is not a clear picture of the relative importance of different inherent host factors. A better understanding of the genetic basis of intrinsic host factors it will make it possible to devise new therapies that overcome genetic deficiencies and to develop screening methods for early detection of susceptible individuals. There is very likely a strong familial predisposition to RUTIs, and a genetically determined susceptibility to severe bladder and kidney infections has been demonstrated in mice. Specific genes that increase bacterial infectivity or impair effective immune responses have not yet been identified in mice or humans. Innate and adaptive immune responses play major roles in resolving UTIs and preventing upper tract infections; however, the exact nature of these responses, their interdependence, and their genetic basis is not fully understood. Therefore, the overall goal of the proposed research is to use genomic approaches and methods to elucidate the genetics of UTI susceptibility and to delineate intrinsic host factors and immune functions that are important for host resistance to UTIs. The specific aims of this proposal are: 1) to test the hypothesis that specific genetic loci in mice are associated with increased susceptibility or resistance to induced E. coil bladder and kidney infections by genetic linkage analysis of UTI-resistant and susceptible mice using DNA microsatellite chromosomal markers and selectively breed strains of mice that are congenic for these resistance genes and 2) to test the hypothesis that genes associated with resistance to bladder and kidney infections induced by one strain of uropathogenic E. coil confer resistance to similar infections caused by other E. coli strains or non-E, coil bacteria. These objectives will be accomplished using a well-established mouse model of ascending UTI, genetic linkage analysis, and evaluation of resistance to uropathogens in congenic mice. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •

Project Title: GLOBAL REGULATORY NETWORKS IN ESCHERICHIA COLI Principal Investigator & Institution: Hatfield, G Wesley.; Professor; Microbiol & Molecular Genetics; University of California Irvine Irvine, Ca 926977600 Timing: Fiscal Year 2003; Project Start 19-SEP-2003; Project End 31-AUG-2007 Summary: (provided by applicant): We have previously described DNA supercoilingdependent mechanisms involving protein (IHF or FIS)- mediated translocation of local superhelical energy from one supercoiling-induced duplex destabilized (SIDD) region on the chromosome to another that serve to coordinate the basal levels of expression of the itvGMEDA, leuV, and ilvYC operons of the ilv regulon of Escherichia coli, both with one another and with the nutritional and environmental states of the cell. Here we propose to employ computational and biological methods to determine the extent to which these mechanisms are used for the global regulation of gene expression in this model organism. More specifically, we will use methods involving computational prediction and experimental verification to bring together three separate lines of inquiry to determine all the genes of E. coli that have the catenation of properties needed for IHF-mediated regulation by a mechanism involving a binding-induced transmission of

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E. coli

destabilization. First, we will use computational methods to predict the locations of all the SIDD sites on the E. coli chromosome at superhelical densities encountered in otherwise isogenic wild-type, topoisomerase (topA, or gyrB) deficient E. coli strains. Second, we will develop and apply a novel method to computationally search the E. coli genome to identify all high affinity IHF binding sites. Third, we will use DNA microarrays to obtain gene expression profiles in IHF + and IHF- cells at the superhelical densities encountered in these strains. These data will allow us to identify genes (operons) that are regulated either by DNA supercoiling, or by IHF, or both. Genes whose upstream flanks contain a SIDD site that coincides with or overlaps a strong IHF binding site, and which are shown to have IHF dependent expression will be identified, and subjected to further experimental study to verify: l) that superhelicity destabilizes the predicted SIDD site; 2) that IHF binds at the predicted location; 3) that changes in duplex destabilization patterns alone, without changes in the local base sequence, affect gene regulation; and 4) that IHF binding regulates this expression in a DNAsupercoiling-dependent manner in an in vitro system. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •

Project Title: GROWTH AND COLONIZATION OF THE INTESTINE BY E COLI Principal Investigator & Institution: Conway, Tyrrell; Associate Professor; Botany and Microbiology; University of Oklahoma Norman Office of Research Services Norman, Ok 73019 Timing: Fiscal Year 2001; Project Start 15-JUN-2000; Project End 31-MAY-2004 Summary: To colonize an animal host, bacteria must acquire nutrients for growth. However, despite extensive research, next to nothing is known about the nutrients and metabolic pathways used in situ by the 400-500 species which inhabit the mammalian large intestine. The proposed research uses functional genomics technology to investigate the acquisition of nutrients by enteric bacteria during the colonization process. Specifically, we will test the hypothesis that induction of the pathways used for catabolism of mucus-derived sugars is essential for colonization of E. coli. Global transcription assays will be used to identify regulons induced for growth on the complex mixture of nutrients present in intestinal mucus. Probes prepared from cells grown on minimal media containing cecal mucus will be hybridized to DNA arrays of all E. coli genes. Pathways induced in situ for growth on mucus will be identified by analyzing global transcription patterns of E. coli cells in the ceca of experimentally colonized germ-free mice. Pathways which contribute to the ability of E. coli to successfully compete with the 400-500 other species in the large intestine will be examined. Mutant strains selectively blocked in specific catabolic pathways will be tested for their ability to colonize mice and green fluorescent protein reporter fusions will be used to determine the temporal and spatial expression of these regulons in individual bacterial cells during colonization. These experiments will identify the distinct physiological roles of individual mucosal sugars in colonization of the large intestine by E. coli, providing knowledge important for addressing the more general question of whether or not metabolic diversity allows pathogenic E. coli strains to colonize in the presence of precolonized strains, thus leading to their ability to cause disease. Knowing precisely which nutrients are essential for colonization should lead to improved strategies for combating infection. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen

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Project Title: H2O2-PRODUCING LACTOBACILLI AND POSTMENOPAUSAL UTI Principal Investigator & Institution: Gupta, Kalpana; Medicine; University of Washington Seattle, Wa 98195 Timing: Fiscal Year 2001; Project Start 30-SEP-2000; Project End 31-AUG-2005 Summary: (adapted from the application) Urinary tract infections affect over 7 million women per year, and the incidence of UTI increases with advancing age. Although marked strides have been made in our understanding of the pathogenesis of UTI in young adult women, the pathogenesis and epidemiology of UTI among postmenopausal women remain poorly understood, especially among the noninstitutionalized segment of the population. Vaginal colonization with E. coli has been shown to be an important event preceding UTI, and it is highly prevalent in postmenopausal women. In vitro studies suggest that the predominant constituents of normal vaginal flora, H202-producing lactobacilli, are inhibitory to E. coli. Our recent data demonstrate that there is, indeed, an inverse relationship between the presence of H202-producing lactobacilli and E. coli vaginal colonization in premenopausal women with recurrent UTI. However, the prevalence of H202-producing lactobacilli, and their relationship to vaginal E. coli colonization and to the incidence of UTI among postmenopausal women has not been characterized. A prospective evaluation of the incidence of and risk factors for UTI in 1000 community-dwelling postmenopausal women (DK43134, Stephan D. Fin, MD, MPH) has been initiated at the Group Health Cooperative of Puget Sound, a population-based HMO in western Washington. Based on our findings in premenopausal women, we are proposing additional studies which will enable us to (1) establish the prevalence of vaginal lactobacilli, characterized by H202 status and by species, in postmenopausal women; (2) examine the relationship between H202-producing lactobacilli and E. coli vaginal colonization; (3) relate this information to the incidence of UTI and asymptomatic bacteriuria in postmenopausal women while accounting for exposures such as estrogen use, diabetes, and antimicrobial use; (4) assess the prevalence of urovirulence genes in E. coli strains causing cystitis in postmenopausal women; and (5) assess the feasibility of using a lactobacillus probiotic to prevent UTI in postmenopausal women. These additional studies will entail a combination of epidemiological, biostatistical, and laboratory methods which, in combination with structured didactic and classroom instruction, will provide an excellent training experience for the development of the Candidate into a successful, independent, clinical investigator. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen

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Project Title: HOST PATHOGENESIS

CELL

KILLING

BY

EPEC:

CENTRAL

ROLE

IN

Principal Investigator & Institution: Crane, John K.; Medicine; State University of New York at Buffalo Suite 211 Ub Commons Amherst, Ny 14228 Timing: Fiscal Year 2003; Project Start 30-SEP-2003; Project End 31-JAN-2006 Summary: (provided by applicant): Enteropathogenic E. coli (EPEC) is a common cause of severe, watery diarrhea in children in developing countries. EPEC is also the prototype of a group of attaching and effacing intestinal pathogens, including enterohemorrhagic E. coli (EHEC, such as O157:H7), Citrobacter rodentium, Hafnia alvei, and EPEC-like E. coli strains of domestic animals. Unlike many other E. coli strains that cause diarrhea, EPEC produces no known toxins, so the way it causes disease has been puzzling. Despite major advances in understanding how EPEC adhere, trigger cytoskeletal rearrangements in the host, and cause other host cell alterations, the

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E. coli

mechanism by which EPEC causes diarrhea has been unclear. The discovery that EPEC triggers host cell death provided an important lead in how EPEC causes disease. The mode of cell death triggered by EPEC has features of both apoptosis (programmed cell death) and necrosis. One of the non-apoptotic features of EPEC-mediated killing is release of adenosine triphosphate (ATP) from the host cell. Once released, ATP is broken down to other adenine nucleotides and adenosine. Adenosine itself acts as a potent secretatagogue, i.e., a stimulator of intestinal fluid and electrolyte secretion, which may cause or contribute to watery diarrhea. The present application seeks to understand how EPEC triggers the ATP release from the host, with a particular focus on the role of the cystic fibrosis transmembrane regulator (CFTR). Other goals include determining the signaling pathways activated by adenosine which activate intestinal secretion, and the determining the extent of release of adenine nucleotides into the intestinal tract of rabbits infected with the EPEC-like pathogens rabbit diarrheagenic E. coli (RDEC-1) and rabbit EPEC (REPEC). Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •

Project Title: HOST DEFENSES AGAINST PATHOGENIC E. COLI Principal Investigator & Institution: Eckmann, Lars; Associate Professor; Medicine; University of California San Diego 9500 Gilman Dr, Dept. 0934 La Jolla, Ca 92093 Timing: Fiscal Year 2003; Project Start 30-SEP-2003; Project End 31-DEC-2007 Summary: (provided by applicant): Pathogenic (diarrheagenic) Escherichia coli are an important cause of food-borne disease in the U.S. and developing countries. Most pathogenic E. coli strains, e.g. EPEC and EHEC, cause mucosal inflammation and disease without deep invasion into the intestinal mucosa or systemic spread. Although much progress has been made in understanding the mechanisms by which pathogenic E. coli cause disease (e.g. toxins), relatively little is known about the host defenses against these pathogens. Based on the lack of deep tissue invasion, we hypothesize that host defenses that operate in the intestinal lumen or at the mucosal surface are key for controlling and eradicating infections with most strains of pathogenic E. coil. Our preliminary data strongly support this notion since we found that B cells are absolutely required for clearance of an EPEC strain in a mouse model of infection. The proposed studies will build on this observation and define the mechanisms of B cell-dependent host defense against pathogenic E. coli, using murine infection models. We will focus specifically on the importance of secretory antibodies as immune effectors of B cells. These studies on specific immune effector mechanisms will be complemented with functional investigations on the regulation of mucosal immune defenses against pathogenic E. coli, with a particular focus on the functions of the immunoregulatory cytokine, IL-6. In addition, we will begin to determine the importance of the intestinal epithelium in orchestrating immune defenses against pathogenic E. coli, as epithelial cells are a focal point of interaction between host and most strains of pathogenic E. coll. These experiments will focus particularly on the physiologic functions of the transcription factor, NF-kappaB, in the intestinal epithelium, using a novel murine model we have developed in which a key component of the NF-kB signaling pathway is deleted selectively from intestinal epithelial cells. The proposed studies have the following Specific Aims: AIM 1. To define the mechanisms of B cell-dependent host defense against pathogenic E. coli. AIM 2. To determine the functions of IL-6 in host defense against pathogenic E. coli. AIM 3. To define the importance of epithelial cell NFkappaB in host defense against pathogenic E. coll. Together, these studies will provide significant new insights into the key host defenses by which the host can eradicate

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infection with pathogenic E. coli, thus providing an important basis for designing immunization strategies against these pathogens. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •

Project Title: IMPACT OF SUPEROXIDE ON THE PHYSIOLOGY OF MODEL BACTERIA Principal Investigator & Institution: Imlay, James A.; Associate Professor of Microbiology; Microbiology; University of Illinois Urbana-Champaign Henry Administration Bldg Champaign, Il 61820 Timing: Fiscal Year 2001; Project Start 01-MAY-1994; Project End 31-MAY-2003 Summary: Oxidative stress has been linked to a variety of human pathologies. It is also critical to bacterial pathogenesis, both because oxygen limits the virulence of microaerophiles and because macrophages use oxidants to attack bacterial invaders. Therefore it is important to achieve a molecular understanding to the mechanisms by which oxygen species damage cells and to the tactics that cells employ to defend themselves. The long-term goal of our lab is to resolve these issues using model bacteria as study subjects. Our current aims are: (1) To explore the molecular basis of the oxygen intolerance of Bacteroides thetaiotaomicron. Preliminary data suggest that B. theta is consigned to anaerobiosis in part because its fumarase, a key iron- sulfur dehydratase, loses activity in air. If this idea is confirmed, then a second problem will be explored: Why does air inactivate such iron-sulfur clusters in B. theta but not in E. coli? (2) To explain unsolved phenotypes of superoxide dismutase-deficient E. coli. SOD mutants cannot synthesize branched-chain amino acids or catabolize non-fermentable carbon sources, and they suffer rapid mutagenesis. These traits have been clearly explained by iron-sulfur cluster damaged. However, these mutants also require reduced sulfur and aromatic amino acids. Circumstantial evidence suggests that these phenotypes, too, evolve from cluster damage. (3) To explain why E. coli synthesizes two aconitases. During oxidative stress E. coli induces a superoxide-resistant isozyme to replace the labile one. This begs the question: Why maintain a labile isozyme at all? One answer may be trivial--that the primary aconitase is kinetically superior--but a more interesting possibility is that the inactivation of the major aconitase is beneficial during periods of iron starvation. (4) To uncover the mechanisms by which the SoxRS regulon defends oxidatively stressed cells. The SoxRS regulon induces several enzymes that provide obvious benefits to superoxide-stressed cells, but the purposes of others are more obscure. It is plausible that some of the latter enzymes help to repair damaged ironsulfur clusters. Other, such as glucose-6-phosphate dehydrogenases, may be understandable only if some of the toxicity of these drugs arises from NADPH depletion rather than from reactive oxygen species. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen

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Project Title: INTERLEUKIN-12 REGULATION BY DR-FIMBRIATED E. COLI Principal Investigator & Institution: Goluszko, Pawel; Obstetrics and Gynecology; University of Texas Medical Br Galveston 301 University Blvd Galveston, Tx 77555 Timing: Fiscal Year 2001; Project Start 01-JUN-2001; Project End 31-MAY-2003 Summary: (Adapted from the Applicant's Abstract): The mechanism of recurrent urinary tract infection (UTI) and its effect on the kidney function is not well understood. The persistence is a characteristic feature of UTI caused by E. coli that express Dr fimbriae. Uropathogenic E. coli strains bearing Dr fimbriae recognize complement regulatory protein-decay accelerating factor (DAF) as their receptor. Interaction of Dr

36

E. coli

fimbriae with DAF is associated with cross-linking of receptor, followed by internalization of Dr-positive E. coli into epithelial cells. DAF is a surface protein anchored in the membrane via the glycolipid glycosylphosphatidyllinositol (GPI). Recent findings indicate that cross-linking of complement regulatory proteins on human monocytes/macrophages by certain intracellular pathogens inhibits the production of key immunoregulatory cytokine, interleukin-12 (IL-12). This finding raises the possibility that Dr-positive E. coli may alter cell immune response by downregulating IL-12, followed by impaired production of interferon , a potent stimulator of bactericidal activity of macrophages. The investigators propose to evaluate in three Specific Aims the general hypothesis that cross-linking of DAF on human monocytes/macrophages by E. coli bearing Dr fimbriae inhibits IL-2 production. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •

Project Title: INTERVENTION STRATEGIES OF HEMORRHAGIC COLITIS AND HUS Principal Investigator & Institution: Boedeker, Edgar C.; Professor; Medicine; University of Maryland Balt Prof School Baltimore, Md 21201 Timing: Fiscal Year 2001; Project Start 01-AUG-2001; Project End 31-JUL-2005 Summary: (provided by applicant): The broad aim of this proposal is to develop and utilize new and established animal model of enterohemorrhagic E. coli (EHEC) infection, in rabbits and dogs, to develop therapeutic regimens to prevent and treat EHEC disease. It is well recognized that shiga-toxin- (Stx)-producing strains of E. coli, acquired by ingestion of inadequately cooked meat, or other contaminated foods, cause hemorrhagic colitis, and may induce fatal hemolytic uremic syndrome (HUS). EHEC strains produce potent protein toxins named Shiga-like toxins (Stxs) because of their relatedness to Shiga toxin of Shigella dysenteriae. In addition, most EHEC share the ability to adhere intimately to intestinal epithelial cells by "attaching and effacing" (A/E)(7) mechanisms (Fig.2). Although EHEC attachment mechanisms may directly contribute to diarrheal disease, and may influence toxin delivery, the most severe intestinal and renal manifestations of EHEC infection result from toxin-mediated damage to vascular endothelium, with tissue edema, inflammatory infiltrates, cytokine production and vascular thrombi. At present, only supportive care is available to prevent the development of the severe, and frequently fatal, complications of EHEC infection. Strategies aimed at decreasing the toxin burden and preventing the interaction of Stxs with their endothelial receptors should prevent or ameliorate disease and damage in target organs (gut, CNS and kidney). Interventions developed in animal models can subsequently be applied to the prevention and management of EHEC disease. E. coli strain RDEC-HI9A infection of rabbits serves as the established animal model of EHEC disease for the initial intervention studies (Aims 1-4). RDEC-H19A, produced by the transfer of the toxin-converting phage H19A of an O26:H11 EHEC to the rabbit entero-pathogenic E. coli RDEC-1, is an attaching and effacing rabbit pathogen which produces high levels of Shiga-like toxin I (Stx-I), colonizes cecum and colon, and induces intestinal disease in rabbits with pathologic changes resembling human EHEC disease. Specific aims (1-4) of the proposal are to use animal models of EHEC infection to: 1). Test the ability of new toxin-receptor analogs, administered paretenteraly or enterically to prevent EHEC disease. 2). Further test the ability of passively administered immunoglobulin with anti-toxic activity to prevent EHEC disease. 3). Further examine whether antibiotic therapy has beneficial or harmful effects on the course of disease. 4). Further develop strategies for active immunization against EHEC using the Stx toxins of EHEC. 5). Specific aim 5 is to utilize canine specific A/E

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strains to produce new STECcapable of infecting dogs, which are susceptible to renal vascular lesions. We will transfer our labeled Stx-1 encoding phage to dog-specific A/E strains of E. coli and test their ability to produce intestinal and renal disease. The clinical studies in dogs will be performed at Kansas State University by Dr. Brad Fenwick who has described the Cutaneous and Renal Glomerular Vasculopathy (CRGV) in greyhound dogs exposed to Stx. 6). Specific Aim 6 is to extend our rabbit and dog models to be able to test similar strategies against EBEC strains expressing Stx-2. We will label and transfer toxin converting phage encoding Stx-2 to rabbit and dog specific A/E strains. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •

Project Title: IRON TRANSPORT AND VIRULENCE IN SHIGELLA AND E COLI Principal Investigator & Institution: Payne, Shelley M.; Professor; Molecular Genetics & Microbiol0gy; University of Texas Austin 101 E. 27Th/Po Box 7726 Austin, Tx 78712 Timing: Fiscal Year 2001; Project Start 30-SEP-1980; Project End 31-MAY-2003 Summary: (adapted from investigator's abstract): Iron acquisition is essential for pathogenic bacteria. In the vertebrate host, however, iron is not readily available, and this scarcity restricts the growth of pathogenic microorganisms and limits their ability to infect and invade. Bacteria have evolved multiple high affinity iron acquisition systems to cope with iron-limiting environments. In spite of considerable characterization of these systems in the laboratory, for most pathogens, the sources of iron used in the host and the relative importance of the different acquisition systems within different niches of the host are poorly understood. The objectives of this study are to determine mechanisms by which gram-negative enteric pathogens obtain iron in the host and to study the possible transmission of iron-acquisition genes and their role in evolution of emerging pathogens. This study will focus on heme transport systems in Shigella and selected Escherichia coli, pathogens which are responsible for considerable morbidity and mortality throughout the world. The first Specific Aim is to continue the characterization of the heme transport locus from Shigella dysenteriae type 1. The PI has found that a nearly identical locus is present in many pathogenic E. coli, including E. coli 0157:H7, and the phylogenetic distribution of this locus is suggestive of horizontal gene transfer. Therefore, the second Specific Aim is to determine whether these genes are mobile and how they may be spreading within the enteric pathogens. The data and strains developed in characterizing the heme transport systems of Shigella and E. coli, together with previous data on high affinity iron transport systems, have placed the PI in the position to now accomplish the third Specific Aim, to determine how Shigella and E. coli acquire iron in vivo. The fourth Specific Aim is to use genetic approaches to understand which genes Shigella specifically expresses in vivo, and to elucidate the role of these genes in Shigella infection. Results obtained from this study will provide basic information on genetics and regulation of potential virulence factors in an important group of pathogens and will provide data useful in design of potential vaccine strains. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen

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Project Title: MECHANISM-BASED NUCLEOTIDE SA

DRUG

SELECTION

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DESIGN:

Principal Investigator & Institution: Ullman, Buddy; Professor; Biochem and Molecular Biology; Oregon Health & Science University Portland, or 972393098 Timing: Fiscal Year 2001; Project Start 30-SEP-1999; Project End 31-AUG-2004

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Summary: (adapted from the application): This R01 application was submitted in response to PA AI-98-100, "National Cooperative Drug Discovery Groups-Opportunistic Infections" (NCDDG-OI) by a group of investigators from the Oregon Health Sciences University, the University of Pennsylvania, and the Yale University School of Medicine. It represents the continuation of a long-term formal collaboration among the investigators of these three institutions, supported since 1991 with a grant under the auspices of the National Cooperative Drug Discovery Group (NCDDG). The major scientific objective of the proposed studies is to integrate genetic, biochemical, and structural studies on key transporters and enzymes of the pyrimidine and purine salvage pathways in Toxoplasma gondii and related apicomplexan parasites, including Cryptosporidium, Sarcocystis, and Plasmodium. The long-term goal will be focused on developing better and more efficacious antiparasitic drugs for these parasites particularly opportunistic pathogens associated with AIDS. Interference with pyrimidine synthesis has traditionally provided the most effective tool for management of clinical toxoplasmosis. However, despite the fact that (i) all of these pathogens are purine auxotrophs, (ii) the existing precedent of subversive purines as effective treatment for other parasitic diseases, and (iii) that the availability of antiparasitic lead compounds that target either purine or pyrimidine salvage pathways, the latter two pathways have not been extensively explored as targets for chemotherapeutic treatment of either T. gondii or other apicomplexans. Reagents previously developed through this research collaboration include: (1) a genetic map of nucleotide salvage pathways in Toxoplasma; (2) molecular clones encoding T. gondii UPRT, HGXPRT, AK, NTPase, and the parasite's major adenosine transporter; (3) milligram quantities of each of the above soluble enzymes purified to homogeneity, and heterologous systems for transporter expression; (4) high-resolution crystal structures for UPRT, HGXPRT, and AK; and (5) transgenic parasites harboring mutations in (or altered expression of) each of the above genes. These reagents are expected to permit structure-based discovery of new drug classes that target proteins necessary for parasite survival. Currently available molecular, biochemical, and cellular reagents and data that have become available through these studies include: (i) Molecular clones. Full length genomic and cDNA sequences for T. gondii uracil phosphoribosyl transferase (UPRT), nucleoside triphosphate hydrolyze (NTPase), hypoxanthine-guanine-xanthine phosphoribosyl transferase (HGXPRT), adenosine kinase (AK), and the parasite's major adenosine transporter (AT). (ii) Recombinant proteins. E. coli that overexpresses T. gondii UPRT, HGXPRT, AK, or NTPase and effectively provides unlimited quantities of these proteins purified to homogeneity. Functional expression of recombinant AT in a Xenopus oocyte assay system. (iii) Crystal structures. High-resolution three-dimensional crystal structures for the UPRT, HGXPRT, and AK proteins determined by x-ray crystallography. (iv) Transgenic parasites. UPRT-, HGXPRT-, and AK-knockout transgenics created by homologous gene replacement in otherwise syngeneic wild type parasites. AT and xanthine transporter (XT) transgenics isolated by imertional mutagenesis. NTPase-deficient transgenics in which the endogenous enzyme is downregulated by antisense expression. Specific aims for the proposed studies include: (1) performing a detailed biochemical and structural characterization of T. gondii UPRT and AK enzymes. The resolution of the T. gondii UPRT and AK enzymes will be extended and enzyme-substrate and enzyme-product structures determined in order to provide a full understanding of their catalytic mechanisms, and to facilitate the discovery of novel inhibitors through computational methods (see Specific Aim 2). High-resolution crystal structures of a series of site-directed mutant UPRT and AK proteins will also be carried out to assess the roles of key residues in substrate specificity and catalysis. Mutant enzymes will be purified from E. coli for kinetic appraisal, and crystal structures will be determined by molecular modification or molecular

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replacement to ascertain structural changes. The phenotypic consequences of mutations of interest will be tested in intact parasites by replacement of either the wild type UPRT or AK allele with an appropriate targeting construct; (2) developing screens for identifying and evaluating novel classes of potential antiparasitic drugs that target either UPRT or AK. Small-molecule structural databases will be screened computationally using the crystallographically determined high-resolution apo- and substrate- and product-bound UPRT and AK structures to identify novel compounds that may interact with the active sites of either enzyme. Compounds that are computationally predicted to target the active site of the T. gondii UPRT or AK enzymes will be evaluated as potential lead compounds against the purified UPRT or AK enzymes; E. coli expressing T. gondii UPRT or AK cDNAs; and wild type, UPRT- or AK-T. gondii parasites in culture. The crystal structures will be solved for UPRT or AK co-crystallized with promising lead compounds; (3) functionally characterize, localize, and genetically dissect the T. gondii adenosine transporter (AT). AT ligand specificity and kinetic parameters will be determined in detail by functional expression of the AT cDNA in Xenopus laevis oocytes and/or nucleoside transport (NT)-deficient Leishmania donovani. The applicants also plan to use electrophysiologic approaches in the Xenopus expression system to ascertain whether AT is a proton- or Na(+)-coupled symporter that actively concentrates adenosine. Antibodies against AT will be used to determine the subcellular location of AT by immunofluorescence and immunoelectron microscopy. Finally, forward genetic approaches will be implemented to initiate a structure-function analysis of key amino acids of AT that participate in ligand recognition or that govern substrate specificity; (4) isolation of XT cDNA and characterizing the properties of T. gondii XT. The XT gene will be isolated from insertional mutants by marker rescue and used to obtain full-length cDNA clones. Functional properties of XT will be evaluated after heterologous expression of XT cDNA in Xenopus oocytes, and the transporter will be immunolocalized after generating monospecific antibodies; and (5) to crystallize and solve the x-ray structure of the T. gondii NTPase and determine how enzymatic activity is regulated. The NTPase cDNA has been overexpressed in E. coli providing ample and replenishable quantities of monomeric recombinant protein for initial crystallization trials. In parallel, the production, purification, and crystallization of enzymatically active oligomeric NTPase will be pursued. Ultimately, these crystallization experiments will lead to the x-ray structure determination of the NTPase by multiple isomorphous replacement. Concurrent experiments will determine how NTPase functions in AK HGXPRT-, and AT parasites, identify the protein(s) which regulate NTPase enzymatic activity, and evaluate the impact of abrogating NTPase expression on parasite viability. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •

Project Title: MECHANISMS OF DIHYDROOROTATE DEHYDROGENASES Principal Investigator & Institution: Palfey, Bruce A.; Lecturer; Biological Chemistry; University of Michigan at Ann Arbor 3003 South State, Room 1040 Ann Arbor, Mi 481091274 Timing: Fiscal Year 2002; Project Start 01-JAN-2002; Project End 31-DEC-2006 Summary: (provided by applicant) Reaction mechanisms will be determined for the family 1A dihydroorotate dehydrogenase (DHOD) from Lactococcus lactis and Enterococcus faecalis, and the family 2 enzymes from Homo sapiens and Escherichia coli. DHOD, the only redox enzyme in pyrimidine biosynthesis, is an attractive target for drug design in the treatment of many diseases, including malaria, arthritis, and Pneumocystis infections in AIDS patients. The mechanism of reduction of the enzyme-

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bound FMN by dihydroorotate for the two enzymes will be determined under anaerobic conditions through stopped-flow kinetic analyses, including the use of single- and double deuterium substrate isotope effects, solvent isotope effects, and the pH dependence of the rate constants. Mutant L. lactis A and E. coli enzymes will be studied in order to determine the roles that active site residues have in the reaction. The mechanism of oxidation of reduced L. lactis DHOD A by fumarate will be elucidated in stopped-flow experiments that will determine the pH dependence of the reaction, and in double-mixing experiments, the deuterium isotope effects for the transfer of each hydrogen to fumarate. The mechanism(s) of oxidation by quinones of DHOD A and the E. coli enzyme will be determined in stopped-flow experiments utilizing a range of quinone substrates. The ubiquinone isoprenyl chain-length preference of the E. coli enzyme will be determined. Enzyme-ligand interactions will be probed with Raman spectroscopy. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •

Project Title: MECHANISMS OF MICROVASULAR THROMBOSIS IN BABOONS Principal Investigator & Institution: Taylor, Fletcher B.; Professor of Pathology; Oklahoma Medical Research Foundation Oklahoma City, Ok 73104 Timing: Fiscal Year 2001; Project Start 01-DEC-1986; Project End 31-MAR-2003 Summary: (Investigator's abstract) Previous studies have documented the role of inflammatory mediators (e.g., TNF, IL-6), hemostatic mediators (e.g. tissue factor/VIIa), hemostatic regulators (e.g. proteins C and S), and hemostatic modulators (e.g C4b binding protein) in driving and controlling the baboon response to E. coli. The antiinflammatory effects of the hemostatic regulators particularly those of the protein C system, and the recent discovery of the involvement of the endothelial protein C receptor (EPCR) and thrombin activated fibrinolytic inhibitor (TADI) in this system, have led us to study their contribution to its anti-inflammatory and anticoagulant properties. EPCR is the newest member of the endothelial/protein C network and it, like protein C itself, is essential in controlling the response to E. coli. The form of EOCR is unique in that while it inhibits protein C anticoagulant activity in vitro it also inhibits tight neutrophil/endothelial cell interactions under flow conditions. We plan to examine the pathophysiologic relevance of these in vitro observations in primate noninflammatory (thrombin) and inflammatory (E. coli) models of DIC. TAFI, the newest member of fibrinolytic inhibitors which are connected to the protein C network, also is unique in that, (1) while it is activated by the thrombin/thrombomodulin complex, its formation is down regulated by activated protein C which also is generated by this complex, (2) it is a carboxypeptidase with potential anti-inflammatory as well as antifibrinolytic activity. Again the relevance of these in vitro observations is unknown, nor is it known under what pathophysiologic conditions TAFI comes into play. We plan to examine TAFI function in the primate models noted above as well as in the C4bBP/sublethal E. coli model of microvascular thrombosis. Finally, we recently found that the endothelial/protein C network of diabetic baboons failed to mount an anticoagulant response to fXaPCPS. It was only the fibrinolytic "back up" response that saved these animals. We plan to determine which components of the protein C system are responsible for this failure and in addition to assess what effect this diabetic deficiency has on the endothelial susceptibility to inflammatory stress (e.g., TNF, IL-6). Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen

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Project Title: MECHANISMS OF SENSORY PROCESSING IN CHEMOTAXIS Principal Investigator & Institution: Stock, Jeffry B.; Professor; Molecular Biology; Princeton University 4 New South Building Princeton, Nj 085440036 Timing: Fiscal Year 2003; Project Start 01-MAR-1984; Project End 31-MAR-2007 Summary: (provided by applicant): All motile prokaryotes use essentially the same mechanism to monitor the chemistry of their surroundings and navigate toward favorable environmental conditions. The E. coli chemotaxis system is the bestcharacterized example. Sensory-motor regulation is mediated by a densely packed receptor array that is imbedded in a patch of membrane at one pole of the cell. The structure is a fibrous bundle of thousands of transmembrane alpha-helical coiled coils. Chemoattractants bind at homodimeric interfaces between alpha-helices at the outside surface of the membrane. The protein kinase, CheA, binds to the opposite end that extends into the cytoplasm. CheA catalyzes adenosine 5'-triphosphate (ATP)-dependent phosphorylation of a histidine residue within an associated histidine phosphotransfer or HPt domain. The long-term objective of the proposed research is to use E. coli as a model to determine the molecular logic of signal transduction pathways. How does attractant binding between coiled coil subunits at the outside surface of an E. coli cell control kinase activity in the cytoplasm? How are different phosphorylation-induced conformational states used to transmit information? To address these fundamental questions, the architecture of the coiled coil membrane receptor assemblies will be determined using EM and X-ray crystallographic methods. Dynamical properties and distance constraints will be characterized by fluorescence resonance energy transfer (FRET) measurements. Kinetic studies of CheA phosphotransfer reactions will provide insights concerning kinase regulation and enzymology. In addition to focusing on these structural and kinetic parameters, an effort will be made to characterize the behavioral responses of E. coli in complex environments in order to better assess the information processing capabilities of receptor-kinase signaling complexes. These studies will provide a foundation for understanding general mechanisms that underlie Type I receptor function in both prokaryotic and eukaryotic regulatory systems. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen

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Project Title: MECHANISTIC STUDIES ON A CO2+ DEPENDENT MAP FROM E COLI Principal Investigator & Institution: Holz, Richard C.; Associate Professor; Chemistry and Biochemistry; Utah State University Logan, Ut 84322 Timing: Fiscal Year 2001; Project Start 01-JAN-1999; Project End 31-DEC-2002 Summary: Thee long range goals of this research are to define the reaction mechanism and substrate specificity of the cobalt(II)-dependent methionine aminopeptidase from Escherichia coli (MAP). In eukaryotic as well as in prokaryotic cells, methiomine aminopeptidases selectively cleave methionine residues from the N-termini of terminal polypeptide chains. In the cytosol of eukaryotes, all proteins are initiated with an Nterminal methionine. The composition of mature N-termini play important roles in the directed degradation and cellular targeting of proteins involved in signal transduction, protein trafficking, cancer cell growth, and viral infection. Recently, one of the two MAP's found in yeast was shown to be the target of the angiogenic chemotherapeutic agents fumagilln and its analog AGM 1470. Therefore, MAP's appear to play a critical role in the proliferation of endothelial cells and likely serve as important targets for inhibiting the growth and proliferation of tumors. As isolated from several bacterial and mammalian sources, MAPs are maximally stimulated by two g-atoms of Co(II). On the

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other hand, the addition of Zn(II) or Mg(II) to apo- MAP's do not provide active enzymes. The MAP from E. coli has been shown by X-ray crystallography to contain a dinuclear cobalt(II) active site. Therefore, MAP is a member of a new class of cobaltcontaining enzymes that includes mammalian MAP' isolated from both porcine liver and humans. Our approach will be to utilize the X-ray crystal structures of the MAP's from E. coli and P. furiosus in conjunction with site mutagenesis, biochemical, and spectroscopic methods to gain fingerprints of each step in the catalytic mechanism. The MAP from E. coli is an ideal enzyme for a study of this type because it is small, highly soluble, readily available in large amounts, and is capable of being genetically manipulated. The specific aims of this proposal are to: 1) define the structural and magnetic properties of the dicobalt(II) an diiron(II) MAP enzymes, 2) characterize how substrate analog inhibitors interact with both the dicobalt(II) and diiron(II) MAP enzymes, 3) determine whether the nucleophilic hydroxide moiety, a key element in the proposed peptide bond cleavage mechanism, is coordinated to one or both metal ions in MAP, 4) prepare and purify variant enzymes with altered active site carboxylic acid, histidine, threonine, and tyrosine residues, 5) provide evidence for and propose a detailed mechanism for MAP. It is anticipated that the successful completion of the studies described in this proposal will provide new insights into the hydrolytic reaction catalyzed by MAP and will ultimately assist in the design and synthesis of new chemotherapeutic agents targeted specifically to MAP's. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •

Project Title: METABOLIC EFFECTS OF THYROID HORMONE Principal Investigator & Institution: Samuels, Herbert H.; Professor of Medicine; Medicine; New York University School of Medicine 550 1St Ave New York, Ny 10016 Timing: Fiscal Year 2001; Project Start 01-MAR-1976; Project End 31-MAR-2004 Summary: Thyroid hormone receptors (C-erbAs) and retinoic acid receptors (RARs) are members of a subgroup of closely related nuclear receptor proteins. c-erbAs and RAR can each activate certain response elements and both receptors contain a highly conserved domain embedded within the ligand binding region containing a series of "leucine-zipper-like" hydrophobic heptad motifs. Functional studies suggest that the heptad repeat domain mediates homo- and heterodimeric interactions of c-erbA and RAR or interactions with other factors. Chick c-erbA-alpha and human RAR-alpha have been expressed in E. coli and purified to near homogeneity. These receptors bind ligand with appropriate affinity and form homo- and hetero-dimers on response elements which are permissive for dimerization. Dimer formation is enhanced by ligand suggesting that ligand mediates transcriptional activation by this mechanism. This application is a comprehensive proposal to define the functional domains involved in cerbA, RAR, and related factors in transcriptional activation. For these studies we constructed a multifunctional bacterial/eucaryotic expression vector (pEXPRESS) which permits site directed mutagenesis and can be used to functionally analyze receptor in eucaryotic cells and to express receptor at high levels in E. coli. Gel shift studies using purified wild-type and mutant receptor proteins and a variety of native and synthetic response elements are proposed to elucidate the "rules" which govern how these receptors recognize functional response elements. These studies will also define receptor domains critical for homo- and hetero-dimer formation, for cooperative interactions between receptors and other factors, and for dominant negative activities. Possible differences in element recognition by c-erbA subtypes (alphal and betal) will also be examined along with studies to understand differences between v-erbA and c-erbA and how c-erbA-alpha2 functions as a dominant negative regulator. These studies will be

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complemented by analyzing receptor mutants derived from patients with the thyroid hormone resistance syndrome. Functional studies in mammalian cells will be extended to in vitro transcription with the goal of defining the protein and DNA requirements for transcriptional enhancement by these receptors. Finally, the availability of mg amounts of purified E. coli expressed wild-type c-erbA and its DNA binding domain will allow circular dichroism, fluorescence, and ultraviolet-visible spectroscopy (both proteins), and nuclear magnetic resonance studies (DNA binding domain) to provide structural information to elucidate the functional and physical properties of these proteins at the molecular level. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •

Project Title: METABOLIC ENGINEERING OF POLYKETIDE PRODUCTION IN E.COLI Principal Investigator & Institution: Khosla, Chaitan S.; Professor; Chemical Engineering; Stanford University Stanford, Ca 94305 Timing: Fiscal Year 2003; Project Start 16-JAN-2003; Project End 31-DEC-2005 Summary: (provided by applicant): Polyketide synthases (PKSs) are a family of multienzyme assemblies that catalyze the synthesis of numerous structurally complex and biologically important natural products. Modular PKSs, such as the 6deoxyerythronolide B synthase (DEBS), are a particularly interesting sub-class of PKSs that synthesize complex polyketides such as macrolides. Over the past decade, there has been considerable interest in studying these megasynthases, and in exploiting their modularity and broad substrate specificity for the engineered biosynthesis of "unnatural" natural products. Most products of modular PKSs are produced by relatively uncharacterized bacteria. As a result, every time a new natural product with promising biological properties is discovered, a considerable amount of time and expense must be incurred to obtain reliable quantities of the compound from natural sources, and an even greater investment is demanded before the biosynthetic pathway becomes amenable to rational engineering. An alternative is to develop robust and generally applicable technologies for the heterologous expression of polyketides in wellcharacterized microbial hosts. During the past proposal period, the metabolism of the model bacterium Escherichia coli was engineered to produce 6-deoxyerythronolide B (6dEB), the macrocyclic core of the antibiotic erythromycin. This engineered strain of E. coli harbors modifications in five endogenous genes; it also contains seven new genes from three different heterologous sources. The resulting cellular catalyst converts exogenous propionate into 6dEB in quantities approaching 200 mg/L over a 5-day process. During the next 3-year proposal period, we will focus on improving and extending the properties of E. coli as a host of choice for the biosynthesis of natural and unnatural polyketides. This will be accomplished through a combination of molecular biological tools, metabolic engineering strategies and fermentation technology development. The Specific Aims are: I] Engineering new pathways for precursor and product biosynthesis in E. coli; II] Improved fermentation protocols for enhancing polyketide productivity in E. coli; III] Further improvements in polyketide productivity of E. coli using functional genornic and metabolic engineering approaches; & IV] Heterologous production of two new complex natural products in E. coli. The implications of this research are 3-fold. First, given the availability of scalable protocols for fermenting E. coli to overproduce bioproducts, the ability to synthesize complex polyketides in this heterologous host will bode well for the practical production of these expensive bioactive natural products as well as their engineered derivatives. Second, the use of E. coli as a host for polyketide production opens the door for harnessing E. coli to

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engineer modular PKSs using directed and random approaches. Finally, the project is a good opportunity to train students at the interface of metabolic engineering & natural product biosynthesis. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •

Project Title: MOLECULAR BASIS OF E. COLI ADHESINS IN BLADDER DISORDERS Principal Investigator & Institution: Hultgren, Scott J.; Professor; Molecular Microbiology; Washington University Lindell and Skinker Blvd St. Louis, Mo 63130 Timing: Fiscal Year 2002; Project Start 01-JAN-1997; Project End 31-DEC-2006 Summary: (Adapted from the Applicant's Abstract): Urinary tract infections (UTIs) are common infections that affect a large proportion of the world population and account for significant morbidity and medical expenditures. These infections are most commonly caused by Escherichia coli (E. coli). A long-term goal of this proposal is to understand the processes by which E. coli causes acute, recurrent and chronic UTIs and the sequelae of these infections. An integrated approach will be used that blends a powerful bacterial genetic system, a mouse UTI model, and x-ray crystallography with high-resolution electron microscopy (EM), protein chemistry, carbohydrate chemistry, and tissue culture systems in order to reveal the cellular, molecular, and structural basis for the pathogenesis of these infections. The FimH adhesin present at the tip of type 1 pili has been shown in animal models to mediate binding to the uroplakin-coated lumenal surface of the bladder. The uroplakin receptor complexes recognized by the FimH adhesin will be cloned and used to investigate the consequences of FimHuroplakin interactions. Also, the three dimensional structure of the FimH adhesin will be used to design a panel of site directed mutations to delineate the mannose binding pocket of the FimH adhesin and the structural basis of bacterial colonization of the urinary tract. The adaptive responses to bladder infections and the activation of signals that lead to the release of cytokines and recruitment of neutrophils will be dissected in detail. FimH-mediated attachment to the bladder epithelial cells activates a cascade of innate defenses that leads to rapid exfoliation and proliferation of underlying epithelial cells. The molecular basis of exfoliation will be investigated and its role in protecting the bladder from infection will be studied. The molecular mechanisms by which uropathogenic E. coli are able to invade bladder epithelial cells and evade the host response will be elucidated. Uropathogenic E. coli replicate intracellularly and form "bacterial factories" in the lumenal superficial facet cells of the bladder. The virulence factors required for this process will be identified and studied. Finally, the fluxing of E. coli out of the facet cells and colonization of underlying tissue will be investigated as a mechanism to cause persistent and recurrent infections. These studies will contribute to the development of adhesin-based vaccines to treat and prevent urinary tract infections and their sequelae. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen

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Project Title: MOLECULAR CHAPERONES AND PROTEIN DEGRADATION Principal Investigator & Institution: Goldberg, Alfred L.; Professor; Cell Biology; Harvard University (Medical School) Medical School Campus Boston, Ma 02115 Timing: Fiscal Year 2001; Project Start 01-AUG-1995; Project End 31-JUL-2003 Summary: Bacterial and animal cells selectively degrade proteins with abnormal conformations. This process helps prevent the intracellular accumulation of unfolded proteins in genetic diseases, during heat shock, and with aging. Molecular chaperones,

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in addition to catalyzing protein folding and translocation, play essential roles in this degradative process. During the current funding period the PI has shown that in E. coli the chaperones DnaK, DnaJ, and GrpE are necessary for the rapid degradation of certain unfolded model polypeptides while GroEL, GroES, and Trigger Factor function together in the breakdown of other (abnormal) polypeptides. These chaperones associate with the substrates and appear to release or present them in a conformation that facilitates proteolytic digestion. In yeast the PI has shown that the DnaJ homolog Ydj1 and Hsp70 of the SSA family are essential for ubiquitin conjugation to abnormal proteins and certain regulatory proteins by binding and enhancing the susceptibility for ubiquitination. The current grant is comprised of four specific aims. Specific Aim A will continue studies on the roles of GroEL/ES/TF in the degradation of the recombinant model substrate CRAG by delineating discrete steps in the initial fragmentation. These studies will combine proteolytic susceptibility studies, mass spec analysis of peptide products, and direct structure determination by EM tomography in collaboration Wolfgang Baumeister. Other studies will test whether the model CRAG substrate is degraded through an analogous chaperone dependent pathway in yeast, allowing the use of yeast genetics to dissect steps. Specific Aim B will focus on clarifying the functions of DnaK and DnaJ in the degradation of the unfolded protein PhoA in E. coli. These studies will use His tagged PhoA and protease dificient strains to isolate intact substrate-chaperone complexes. Specific Aim C will determine the roles of the DnaJ and Hsp70 families in the ubiquitin-proteasome pathway in yeast using model substrates carrying defined degradation signals. This line of investigation will be extended to defined cell free studies as well as studies of the potential role of Sis1 in binding to ubiquitin conjugates prior to degradation by the proteasome. Specific Aim D will define the chaperone like function of the PAN and HslU ATPases which support protein breakdown by proteasome homologs in archeabacteria and E. coli. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •

Project Title: NEUROENDOCRINE MEDIATION OF E. COLI 0157:H7 INFECTION Principal Investigator & Institution: Lyte, Mark; Professor; Minneapolis Medical Research Fdn, Inc. 600 Hfa Bldg Minneapolis, Mn 55404 Timing: Fiscal Year 2001; Project Start 01-APR-2000; Project End 31-MAR-2004 Summary: This application proposes the new theory of directed neuroendocrinebacterial interactions as a mechanism governing the ability of an enteric pathogen to infect a host. This hypothesis is based on the in vitro and in vivo ability of the neuroendocrine hormone norepinephrine (NE) to increase growth and production of virulence-associated factors of the enteric pathogen Escherichia coli O157:H7. High concentration of NE occur in foods such as ground beef which are contaminated by E. coli O157:H7. Equally high concentrations of NE also occur within the gastrointestinal tract due to enteric nervous system activity. The proposed research will therefore examine whether the presence of NE from the time of E. coli O157:H7 contamination of NE-rich foods to infection within the gut may be a factor mediating the development of hemorrhagic colitis. Results from this laboratory have shown that the effect of NE on E. coli O157:H7 contamination of NE-rich foods to infection within the gut may be a factor mediating the development of hemorrhagic colitis. Results from this laboratory have shown that the effect of NE on E. coli O157: H7 is due to the production of an autoinducer of growth. Thus, our Specific Aims are: 1) To determine the ability of a purified diet supplemented with levels of NE found in commonly contaminated foods to "prime" E. coli O157:H7 for the NE-rich environment within the gastrointestinal system; 2) To examine the ability of E. coli O157:H7 isolated from gastrointestinal trat of

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stressed and non-stressed mice since differences in luminal levels of NE between stressed and control animals would provide greater understanding of the recognized ability of stress to alter susceptibility to colitis; 4) To determine the ability of stress of alter the susceptibility of mice to oral challenge with E. coli O157:H7 exposed in vitro to control of NE supplemented diets; 5) To examine whether blockage of NE release within the gastrointestinal tract can alter susceptibility to challenge with E. coli P157:H7; and 6) To purify the serum-bound form of the NE-induced E. coli O157:H7 autoinducer of growth and determine its structure which may provide the basis for the development of agents to specifically interrupt bacterial division as well as identify the gene(s) involved in its production. Collectively, the above aims will seek to establish a direct cause and effect relationship between the NE content within food and the gastrointestinal trat to influence the ability of E. coli O157:H7 to cause infection. The demonstration of direct neuroendocrine-bacterial interaction as a mechanism in the pathogenesis of E. coli O157:H7 infection may yield new treatments for both the prevention and treatment of hemorrhagic colitis. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •

Project Title: NEW KETOLIDE ANTIBACTERIAL DRUGS Principal Investigator & Institution: Hutchinson, Charles R.; Edward Leete Professor; Kosan Biosciences 3832 Bay Center Pl Hayward, Ca 94545 Timing: Fiscal Year 2003; Project Start 15-FEB-2002; Project End 31-MAY-2006 Summary: (provided by applicant): The long-term goal of this Phase II proposal is the production of new ketolide antibiotics with potent antibacterial activity against macrolide-susceptible and macrolide-resistant bacterial pathogens of humans. In Phase I research, we successfully developed a biological process for production of 15-R-6deoxyerythronolide B, the biochemical precursor of 15-R-erythromycins (R=various chemical groups), that involves expression of the 6-deoxyerythronolide B (DEBS) polyketide synthase (PKS) genes in an Escherichia coli strain carrying the requisite PKS substrate supply genes. In Phase II this process will be optimized for large-scale production of the desired 15-R-6-deoxyerythronolide B (15-R-6dEB) by feeding the 5R-3hydroxy-2-methylpentanoic acid N-acetylcysteamine thioester ("diketide-SNAC") to an E. coli strain expressing the engineered DEBS1 module 2/DEBS2/DEBS3 genes. The resulting 15-R-6dEB will be used subsequently to produce a lead ketolide Kosan has discovered in partnership with another company. The specific aims for the Phase II research are: 1) to determine the relationship between the titer of polyketide produced and the level of DEBS PKS, substrate supply enzymes and substrates. These data will help us design and construct a recombinant E. coli strain that produces >100 mg/L of 15-R-6dEB in a diketide-fed, shake flask fermentation. 2) To isolate, by random mutagenesis of an E. coli strain bearing DEBS PKS and substrate supply genes, mutant strains with a >10-fold increase in 15-R-6dEB titer in a diketide-fed, shake flask fermentation. The improved genetic background of these mutants is expected to enhance the performance of the optimum arrangement of the DEBS PKS and substrate supply genes created in Specific Aim 1. 3) To introduce the optimal metabolically engineered DEBS PKS and substrate supply genes from Specific Aim 1 into the E. coli strain from Specific Aim 2 to create an E. coli recombinant strain that produces >250 mg/L of 15-R-6dEB in a diketide-fed, shake flask fermentation. 4) To optimize the physiological and process parameters for maximum production of 15-R-6dEB at >1 g/L by high cell density E. coli cultures in a 2 liter stirred fermentor. This will be done with a strain obtained through achievement of Specific Aim 3. Several of the ketolide series of analogs based on 15-R-erythromycin A have excellent in vitro and in vivo antibacterial

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activity, comparable to or better than the leading ketolides in current clinical trials or approved by the FDA for specific uses. We intend to move the best compound to preclinical testing in collaboration with our partner. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •

Project Title: NOVEL E. COLI 0157:H7 INTESTINAL COLONIZATION FACTORS Principal Investigator & Institution: Kaper, James B.; Professor; Microbiology and Immunology; University of Maryland Balt Prof School Baltimore, Md 21201 Timing: Fiscal Year 2001; Project Start 30-SEP-2000; Project End 31-JUL-2005 Summary: (adapted from the application) The essential first stage of typical E. coli O157:H7 infection is colonization of the intestinal tract. To date, only one bacterial factor has been shown to mediate intestinal adherence by O157:H7, the outer membrane protein intimin which was originally discovered in the Principal Investigator's laboratory. However, a variety of observations indicate that additional intestinal colonization factors may play a role in disease due to E. coli O157:H7 and Shiga toxinproducing E. coli of serotypes other than O157:H7 The overall goal of this project is to investigate the mechanisms by which E. coli O157:H7 and non-O157:H7 enterohemorrhagic E. coli colonize the intestine. Our approach will be focused in four specific aims. Three of the specific aims will focus on characterization of three newly discovered potential colonization factors of EHEC. Two of these factors have homology to previously described adhesins in other enteric pathogens and the third factor has no obvious homology to previously described adhesins. For each of these factors we will construct isogenic non-polar mutations in the structural gene and test the mutants for decreased adherence in differential intestinal epithelial cell lines, freshly harvested human intestinal epithelial cells, and in a gnotobiotic piglet model of disease. The demonstrated involvement of any of the three novel colonization factors in intestinal adherence would provide new targets for vaccine development. The fourth aim will focus on a novel regulatory mechanism of the best-characterized EHEC colonization factor, intimin. We recently showed that in vitro expression of the intimin adhesin and the type III secretion system encoded on the LEE pathogenicity island is positively regulated by autoinducer molecules expressed by normal flora E. coli strains, i.e., quorum sensing. We propose to test whether quorum sensing is active in vivo by constructing an O157:H7 derivative that no longer responds to quorum sensing and testing it for colonization in a pig model. If quorum sensing is active in vivo, this would open up a new area for potential therapeutic intervention based on inhibiting the quorum sensing mechanism, thereby decreasing expression of intestinal colonization factors. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen

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Project Title: NUCLEASES IN DNA REPAIR AND RECOMBINATION Principal Investigator & Institution: Lovett, Susan T.; Associate Professor; None; Brandeis University 415 South Street Waltham, Ma 024549110 Timing: Fiscal Year 2001; Project Start 01-APR-1990; Project End 31-MAR-2003 Summary: Cells employ numerous DNA repair and mutation avoidance mechanisms to protect genetic integrity. In the absence of these important processes, cells suffer mutations, chromosomal aberrations or death. Repair-deficient human syndromes have been identified and include neurological and immunological defects, cancer-proneness and premature aging. One common feature of many DNA repair and mutation avoidance mechanisms is the degradation of DNA, accomplished by DNA exonuclease

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proteins. Exonucleases excise offending DNA lesions or replication errors and promote recombinational repair of broken chromosomes. Exonucleases also prevent inappropriate genetic rearrangements that lead to mutation. Exonucleases produce molecular signals for cell division arrest when the cell is confronted with DNA damaged. A molecular understanding of DNA recombination, repair and mutagenesis will require knowledge of the exonucleases that participate in these processes. Our objective is to define recombination and repair exonucleases of E. coli and Saccharomyces cereviseae. We seek to understand their biochemical properties, their molecular partners and what roles they play in vivo. The RecJ exonuclease from E. coli has been the focus of much of our previous investigation. We have shown that RecJ is a member of a large family of proteins found in archaebacteria, eubacteria and eukaryotes. We will continue to analyze the structure and function of this protein. Physical or functional interactions of RecJ exonuclease with other proteins involved in DNA replication or repair will be assayed. We have identified two new exonucleases from the bacterium E. coli. We will continue to characterize their biochemistry and will analyze mutants in these exonucleases for genetic stability, recombination and DNA repair defects. As it is clear that some of these functions are genetically redundant, multiple mutants in these and other genes will assessed for genetic properties. Physical monitoring of DNA repair and assessment of SOS regulation will be performed in ssExo mutants. A third putative DNA exonuclease from E. coli will be assayed for activity on oligonucleotides. Mutants and genetic suppressors of this function will be characterized. We will investigate the role of putative 3' exonucleases (based on sequence similarity) from the yeast Saccharomyces cerevisiae. The genes will be expressed in E. coli to verify if they encode exonucleases. Mutants in conservied residues will be examined for biological effects. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •

Project Title: PATHOGENIC MECHANISMS AND INTERVENTION STRATEGIES IN HUS Principal Investigator & Institution: Siegler, Richard L.; Professor, Division Chief; Pediatrics; University of Utah 200 S University St Salt Lake City, Ut 84112 Timing: Fiscal Year 2000; Project Start 30-SEP-1996; Project End 31-AUG-2004 Summary: Post-diarrheal uremic syndrome (HUS) is the most common cause of acute renal failure in infants and young children, and is a substantial cause of chronic kidney damage and failure. The diarrhea is caused by enterohemorrhagic E. coli (e.g., E. coli 0157:H7) that produces potent cytotoxins known as Shiga-like toxins (SLTs) or Verotoxins (VTs). There is strong circumstantial evidence that SLT and Lipopolysaccharide (LPS) gain access to the circulation from the gut, damage renal endothelial cells and activate a complex pathogenic cascade that results in oliguric renal failure. Our limited understanding of the pathogenic cascade, however, has hampered efforts to develop effective intervention strategies. A non-human primate model (baboon) will be used to test the hypothesis that acute renal failure in SLT/LPS induced HUS results from increased prothrombotic, vasoconstrictive, and lipid peroxidation activity coupled to decreased antithrombotic, vasodilatory, and antioxidant activity, and that correcting this imbalance favorably influences the natural history of the syndrome. More specifically, purified SLT-I and LPS will be infused into baboons, after which the magnitude and sequence of the appearance of markers of endothelial and renal tubular cell injury, lipid peroxidation, white blood cell, platelet and coagulation cascade activation, and substance that modulate thrombosis and vascular tone will be determined. The importance of LPS in the pathogenic cascade will be measured by

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determining if LPS causes up-regulation of renal GB3 toxin receptors, and if so, if upregulation is associated with cytokine production. Once the pathogenic cascade has been characterized, the up-regulated prothrombotic, vasoconstrictive, and lipid peroxidation systems will be selectively and collectively blocked, and the down-regulated antithrombotic, vasodilatory and antioxidant systems will be stimulated. This will provide information concerning the relative importance of each in the pathogenesis of the syndrome, and will identify intervention strategies that can be used to interrupt the pathogenic cascade and thereby prevent full expression of the syndrome. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •

Project Title: PHOP/PHOQ DELETED S TYPHI VACCINE STRAINS Principal Investigator & Institution: Hohmann, Elizabeth L.; Assistant Professor of Medicine; Massachusetts General Hospital 55 Fruit St Boston, Ma 02114 Timing: Fiscal Year 2001; Project Start 15-APR-1999; Project End 31-MAR-2003 Summary: Vaccination is an effective and economical method of preventing disease, and multivalent, orally administered vaccines will have the widest clinical application. Attenuated Salmonella have been successfully studied in murine models as live vectors for delivery of heterologous antigens to the gastrointestinal immune system. Studies in humans have been limited, and variables important for immunogenicity in humans have not been clearly defined. A Salmonella typhi strain (Ty800) deleted for the phoP/phoQ virulence regulon of Salmonellae is very safe and immunogenic in human volunteers, and this strain has been modified to express clinically relevant heterologous antigens. This proposal describes a program of translational research designed to evaluate Salmonella-based vaccine regimens in humans utilizing bivalent S. typhi vaccine strains. These studies emphasize rational modification of clinically acceptable human vaccine strains and vaccination regimens which may alter immunogenicity of heterologous antigens such as type of antigen, location of antigen within the bacterial cell and mechanism of expression or secretion. Using an established IRB-approved human study protocol, adult volunteers are vaccinated, followed for safety and vaccine shedding, and intensively evaluated for evidence of mucosal, humoral and cellular immune-responses to both S. typhi antigens and the relevant heterologous antigens. A sequential oral vaccination regimen consisting of a S. typhi vaccine strain expressing cytoplasmic Helicobacter pylori urease followed by purified recombinant urease and E. coli heat labile toxin adjuvant will be tested in adult volunteers seronegative for H. pylori. An S. typhi strain expressing a fusion antigen of E. coli hemolysin A linked to urease B which is secreted from the bacterial cell will be studied to determine whether secretion alters immunogenicity in this system. Additional constructs will be generated which express either an E. coli heat labile toxin mutant or an E. coli colonization factor antigen (CFA/I). These new strains will be evaluated in vitro and subsequently tested in volunteers to determine whether these molecules with different structures or subcellular location can engender systemic and/or mucosal immune responses. These studies are designed to provide novel human safety and immunogenicity data which is vital to the clinical development of live bacterial vaccine vectors. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen

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Project Title: PRODUCTION AND FUNCTION OF E COLI VESICLES Principal Investigator & Institution: Kuehn, Margarthe J.; Assistant Professor; Biochemistry; Duke University Durham, Nc 27706 Timing: Fiscal Year 2002; Project Start 01-SEP-2002; Project End 31-AUG-2004

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Summary: (provided by applicant): Escherichia coli, as well as all of its gram-negative relatives studied to date, undergo a process of vesiculation, or pinching-off, of the outer membrane. Vesicles have been shown to be capable of fusion with both bacterial and eukaryotic membranes, delivering soluble and membrane components during this process. Although their presence has been recognized for decades, bacterial outer membrane vesicles have yet to be investigated at a basic genetic and biochemical level. In preliminary work, methods have been developed to isolate and purify vesicles from E. coli. The first objective is a genetic approach to elucidate the cellular machinery that produces vesicles. Randomly generated E. coli mutants will be screened for defects in vesicle production. The second objective is to how vesicles benefit the "mother cell" under normal physiological conditions and under stressful growth conditions. The ability of vesicles to communicate between cells may help in a competitive growth environment and to disseminate genetic information. Using biochemical assays, we will investigate vesicle-mediated transmission of proteins, lipids and nucleic acids. Artificial liposomes have been shown to fuse with bacterial membranes in vitro and these experiments provide a basis to begin studying vesicle membrane characteristics that may be important for fusion. Under stressful growth conditions, the vesicle pathway may be co-opted to allow quick remodeling of the outer membrane. The contribution of vesicles to the dramatic switch in lipopolysaccharide composition after cold shock will be analyzed. Further, vesiculation mutants will be used to investigate the function of vesicles during a bacterial response to diverse environmental stresses. The aims of the proposal are distinct and do not depend on one another, yet build on each other to address the project hypotheses. This powerful combination of genetics and biochemistry will set a foundation for future discoveries in this basic area of bacterial physiology. It is anticipated that these studies will reveal general principles of membrane dynamics, while also highlighting new concepts unique to bacterial membranes. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •

Project Title: PROKARYOTIC RNA METABOLISM Principal Investigator & Institution: Belasco, Joel G.; Microbiology; New York University School of Medicine 550 1St Ave New York, Ny 10016 Timing: Fiscal Year 2001; Project Start 01-JAN-1986; Project End 31-MAR-2005 Summary: These investigations will focus on elucidating the process of mRNA degradation in Escherichia coli. The goal of these studies will be to identify and characterize RNA elements responsible for differences in mRNA stability, to define the features of a key bacterial ribonuclease that determine its specificity and function, and to elucidate important aspects of the mechanism by which this ribonuclease acts. Molecular biological, biochemical, and genetic methods will be employed. Particular attention will be devoted to RNA degradation by RNase E, a ribonuclease thought to control the principal pathway for mRNA decay in E. coli. First, we will examine how the rate of internal RNA cleavage by this endonuclease is controlled by the phosphorylation state of the RNA 5' terminus. In addition, we will investigate the RNA and protein elements that govern the ability of RNase E to autoregulate its synthesis in E. coli, taking advantage of a powerful and convenient genetic system that we have developed for this purpose. Finally, we will examine the role of 5'-terminal RNA secondary structure as an impediment to mRNA degradation by the related E. coli endonuclease CafA. The results of these studies should enhance our knowledge of a fundamental aspect of gene regulation that presently is poorly understood. This knowledge should ultimately be of value in maximizing bacterial production of medically useful proteins

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and in clarifying a biological regulatory mechanism that can play an important role in microbial pathogenesis. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •

Project Title: PROTEIN SELF-ASSEMBLY IN MODEL MICROORGANISMS Principal Investigator & Institution: Hu, James C.; Associate Professor; Biochemistry and Biophysics; Texas A&M University System College Station, Tx 778433578 Timing: Fiscal Year 2001; Project Start 01-AUG-2001; Project End 31-JUL-2005 Summary: (provided by applicant): With complete genome sequences available, it is now possible to examine all of the proteins in a genome for involvement in multisubunit assemblies. How different proteins are able to form stable complexes is of fundamental interest from the perspective of protein structure and folding. In addition, identifying proteins that physically interact can provide valuable clues about their biochemical and biological functions. Mapping domains within proteins that are responsible for oligomerization is an important part of structure-function analysis. This application describes experiments to simultaneously identify and localize oligomerization domains on a genome-wide scale. Genomic DNA fragments from S. cerevisiae that encode motifs that can self-assemble will be identified by a genetic approach based on gene fusion methods using E. coli as a host. Libraries of yeast DNA fragments cloned as gene fusions to the DNA binding domain of bacteriophage lambda cI repressor will be subjected to selection for repressor activity, which requires assembly into dimers or higher oligomers. Initial characterization of candidate motifs will exploit the unique ability of the repressor system to distinguish between dimers and higher oligomeric forms in vivo. While the selection and characterization of oligomerization domains from yeast is in progress, the search will be extended to find self-assembling domains from two bacteria, E. coli and M. tuberculosis, and two filamentous fungi, N. crassa and A. fumigatus. Although the primary focus of this proposal is on homotypic interactions, methods will be developed to use combinations of libraries in E. coli-based two-hybrid systems to examine protein motifs from S. cerevisiae that are sufficient to form heterotypic complexes. Oligomerization domains will be expressed and purified from E. coli. Size exclusion chromatography and analytical ultracentrifugation will be used to determine their oligomerization states. The boundaries of the domains that are necessary and sufficient to form stable complexes will be determined by partial proteolysis, followed by analysis of protease resistant fragments by N-terminal peptide sequencing and mass spectrometry. Structures of soluble oligomerization domains will be determined by X-ray crystallography. Expression vectors will be developed to use the oligomerization domains as "dominant negative" inhibitors in S. cerevisiae and in E. coli. This work will contribute to human health by providing important insights into protein taxonomy, materials for protein design, new tools for genetic studies in model organisms (S. cerevisiae and E. coli) and important human pathogens (M. tuberculosis and A. fumigatus), and new drug targets based on protein-protein interactions. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen

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Project Title: REGULATION

PURINE

BIOSYNTHESIS

ENZYMES-MECHANISMS

Principal Investigator & Institution: Stubbe, Joanne; Massachusetts Institute of Technology Cambridge, Ma 02139

Professor;

Timing: Fiscal Year 2001; Project Start 01-SEP-1987; Project End 31-DEC-2003

AND

Chemistry;

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Summary: We have used the purine biosynthetic pathway as a paradigm for thinking about the importance of transient protein/protein interactions in the direct transfer (Channeling) of chemically unstable intermediates between successive enzymes in metabolic pathways. The over-expression of all the enzymes in this pathway from E. coli and the availability of structures of 6 of the 11 enzymes from E. coli, make this an excellent pathway to examine the channeling question, mechanistic questions, as well as questions about the evolution of a pathway. The product of PurF, the first enzyme in the pathway, is the chemically unstable phosphoribosylamine (PRA). Our in vitro kinetic studies have suggested that PRA is channeled directly to PurD, the second enzyme in the pathway. The availability of structures of PurF from E. coli and B. subtilis and of PurD from E. coli have allowed us to propose a structural model for the channeling of PRA uniquely between enzymes from the same organism. In addition to the availability of the E. coli PurF and PurD, we now have available the B. subtilis PurF and PurD. Kinetic studies in vitro between these proteins from heterologous sources as well as between the two B. subtilis proteins will be examined. Our model predicts that only the ternary complexes of PurF.PRA.PurD from the same organism should channel. The available structures allow us to attach site specifically fluorescent probes to look for the transient interactions between these proteins in vitro and ultimately in vivo. In addition, using homologous recombination methods, the B. subtilis purF ORF will be manipulated to precisely replace the E. coli purF ORF in wild type E. coli. The phenotypic consequences of this replacement will be examined. We have recently obtained the structures of PurK and PurE, the sixth and seventh enzymes in this pathway. We have proposed, that these enzymes as well might channel the chemically unstable N5-CAIR, the product of PurK. Similar experiments to those described for PurF and PurD can now be carried out with PurK and PurE. Finally in addition to PurD, PurK and PurE, we have also obtained the structure of PurM, the 5th enzymes in this pathway. At present most of the structures are wild-typ4e, that is nucleotides are bound. To increase the insight that these structures will provide about function, we will synthesize a variety of potential inhibitors of these enzymes. The liganded structures should provide more specific insight about mechanistic possibilities. The structures have already suggested a variety of mechanistic experiments that will be carried out. The commonality of the ribose-5 P moiety of all the intermediates in this pathway, the fact that PurD, PurK and PurT are structurally homologous and catalyze similar chemistries, and that PurL and PurM appear also to be structurally and mechanistically related, provides food for thought about the evolution of a biosynthetic pathway. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •

Project Title: QUANTITATIVE IN VIVO IN VITRO STUDIES OF CELL PROCESSES Principal Investigator & Institution: Record, M. Thomas.; Professor; Biochemistry; University of Wisconsin Madison 750 University Ave Madison, Wi 53706 Timing: Fiscal Year 2001; Project Start 01-AUG-1992; Project End 31-JUL-2004 Summary: from applicant's abstract): In this project the principal investigator and colleagues propose to quantify: 1) the major changes in the types and amounts of cytoplasmic and periplasmic solutes and in amounts of cell and compartment water which allow E. coli to grow over a very wide range of external osmolalities; and 2) the accompanying large changes in turgor pressure across the cell wall. By comparison with in vitro effects of solutes, these large changes in concentrations of cytoplasmic solutes and biopolymers should individually perturb most cell processes, but collectively do not. Equally striking are the large changes in amount of cytoplasmic water, which

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measurements of turgor pressure show are not accompanied by large changes in water activity. The long term goals are: 1) to understand E. coli as a chemical and osmotic system; 2) to relate studies of solute-biopolymer interactions in vitro to solute effects on biopolymer processes in vitro and in vivo; and 3) to understand the global compensation mechanisms by which cell processes are buffered against changes in solute concentrations, and the molecular basis for the stimulatory effect on growth rate of metabolically-inert "osmoprotectant" solutes. The specific aims are: 1) to determine the physiological and biochemical responses of E. coli to the stress of high and low osmolality environments; 2) to quantify the interactions of E. coli osmolytes, other solutes and crowding agents with biopolymers in vitro in order to obtain structural predictions/interpretations of solute effects on biopolymer processes; and 3) to test by quantitative in vivo and in vitro studies the proposal that global compensation mechanisms involving balances between destabilizing effects of accumulated solutes, stabilizing effects of excluded solutes, and macromolecular crowding maintain biopolymer structure and function, allowing cell growth over a wide range of osmolalities at a rate which increases with the amount of free cytoplasmic water. The in vivo studies use standard analytical methods for solutes and a differential radioisotope assay for compartment water; the principal investigator proposes a quantitative application of gene array technology to analyze changes in amounts of individual mRNAs vs. growth osmolality. They use a novel application of osmometry for in vitro studies of solute-biopolymer interactions and use rapid-quench mixing and radioisotope and enzymatic assays to characterize solute effects on biopolymer processes. An understanding of the osmotic behavior of E. coli, the best characterized living system, is of practical as well as fundamental significance, both as a model for volume and osmotic regulation in kidney and many other eucaryotic cells and in combating both osmotically-induced virulence and tolerance of pathogenic strains of E. coli and Salmonella typhimurium to desiccation, heat, peroxide and urea. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •

Project Title: RAPID FOOD AND BEVERAGE PATHOGEN DETECTION Principal Investigator & Institution: U'ren, Jack R.; Director of Research; Saigene Corporation 7126 180Th Ave Ne, Ste C-104 Redmond, Wa 98052 Timing: Fiscal Year 2001; Project Start 01-MAY-2001; Project End 31-JAN-2002 Summary: (Verbatim from Applicant's Abstract):Tens of millions of cases of food-borne and beverage-borne illnesses occur in the United States every year with an estimated cost to the economy of 1-10 billion dollars. The emergence of new pathogenic strains, such as E. coli 0157:H7, seem to have a particularly disastrous effect on young children. In the Pacific Northwest in 1993 over 700 people were sickened from undercooked ground beef, 55 that developed hemolytic uremic syndrome (HUS), and four died. The overall goal of this program is to develop a rapid pathogen detection system with single cell detection sensitivity and assay times of less than a few hours. Assay specificity will be achieved through the use of commercially available pathogen specific antibodies to cell surface antigens. Single cell assay sensitivity will be achieved by a novel electronic imaging of samples collected on filter media that have been reacted with an enzyme labeled specific antibody. By including a short growth step, viable cells can be distinguished from pathogens killed by the food preparation process. Assay protocols designed to detect E. coil and Salmonella will be developed in Phase I and expanded to include E. coli 0157:H7, Cryptosporidium, Listeria, Campylobacter, and Yersina in Phase II. PROPOSED COMMERCIAL APPLICATION: Current AOAC standard culture methods for food pathogen detection require between five and ten days. Meanwhile the

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product is held for shipment which increases storage costs and decrease shelf-life. More rapid systems can save the food industry many millions of dollars and greatly improve the safety and quality of our food supply. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •

Project Title: READOUT'

'RECODING:

DYNAMIC

REPROGRAMMING

OF

GENETIC

Principal Investigator & Institution: Atkins, John F.; Research Professor; Human Genetics; University of Utah 200 S University St Salt Lake City, Ut 84112 Timing: Fiscal Year 2001; Project Start 01-AUG-1992; Project End 31-MAR-2005 Summary: The translational bypassing in the Phage T4 gene 60 represents the efficient synthesis of one protein from two coding sequences that are separated by 50 nucleotides in mature mRNA. This example challenges our knowledge of protein synthesis and our confidence in predictions of the variety of protein products encoded in genomes. The overall aim of the proposed work is to understand the mechanisms involved in the beststudied case of translational discontiguity. This will be achieved by elucidating why there is a preference for coding resumption after 50 nucleotides. Up-mutants will be isolated and characterize that give efficient bypassing from cassettes with different defects in the gene 60 bypassing signals: poorly functioning matched take-off and landing codon pairs, extended coding gap, extended stem loop and related studies with mutants of nascent peptide affecting frame shifting. Starting with a WT gene 60 bypassing cassette, to isolate down-mutants with screening rather than selection, and repeat in a strain with a single copy of ribosomal RNA genes. To gain functional information from genetic studies about the interacting partners of ribosomal protein L9 that is important for bypassing. To facilitate cryo-electron microscopic studies by a collaborator of bypassing and frameshifting to gain structural information. To investigate pausing in bypassing and frameshifting. Recoding: Redefinition and Frameshifting Reprogramming of the readout of certain mRNAs can cause a different meaning for a code word or alternative reading frames to be accessed. Here, dynamic redefinition of the "stop" codon of Murine Leukemia Virus (MuLV) gag gene and the ribosomal frame-shifting required for expression of mammalian antizyme are to be studied. This frame-shifting serves as the sensor of an autoregulatory circuit. For both redefinition and frame-shifting, signals in mRNA stimulate the efficiency of the nonstandard event at the recoding site. To ascertain if possible structural elements that include the recoding site exist and if so whether they play a synergistic role in antizyme frame shifting and MuLV gag-pol stop codon read through. To determine if there is tissue specificity to the programmed frame-shifting candidate, antizyme 3, by using a transgenic mouse approach. Recoding: Further mechanistic studies partly as a guide for identifying new cases To determine the effects of mutations of E. coli tRNA Gly2 , isolated for their bypassing and frame-shifting properties, on tRNA structure and dynamics. To determine the solution structure of E.coli tRNA Ala GCC because of the evidence for the purine at position 32 influencing frame-shifting. To investigate a role for the base at tRNA position 34 or 37 on E. coli-1 frame-shifting: single tRNA slips at a hexa-nucleotide shift site in distinction to the classical tandem shifts at hepta-nucleotide sites. To keep monitoring newly reported sequences for potential new cases and to respond to suggestions of others who have encountered new cases. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen

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Project Title: RECOMBINOGENIC ENGINEERING OF PATHOGENIC BACTERIA Principal Investigator & Institution: Murphy, Kenan C.; Molecular Genetics & Microbiol; Univ of Massachusetts Med Sch Worcester Office of Research Funding Worcester, Ma 01655 Timing: Fiscal Year 2002; Project Start 01-APR-2002; Project End 31-MAR-2004 Summary: (Provided by applicant): Gene deletion and/or replacement is the single most important tool for definitively identifying critical functions of infectivity and virulence in pathogenic bacteria. Yet the tools available to make such gene replacements in pathogenic bacteria have, for the most part, remained unchanged for the last 10 years. While genome sequencing projects continue to increase the number of open reading frames available for genetic analysis, gene knock-out technology in many bacterial systems remains technically cumbersome, and in some cases, unfeasible. This project is designed to explore a novel methodology for the enhancement of gene replacement in pathogenic bacteria. The Red recombination system from bacteriophage lambda, when expressed in Escherichia coli, generates a hyper-recombinogenic phenotype whereby gene replacement occurs at an extremely high efficiency following transformation with small (2-3 kb) linear DNA substrates. This gene replacement scheme is unique in that plasmid-chromosome co-integrants do not have to be formed (or resolved), and prior cloning of the gene of interest is not required. PCR-generated substrates with as little as 40 bp of flanking homology are substrates for efficient Red-mediated gene replacement. The recombination intermediates generated by lambda Red are channeled into the host recombination pathway. It is this "jump start" in the initiation of recombination that likely plays a key role in the generation of the hyper-rec phenotype of lambda Redcontaining E. coli. Since most bacteria contain homologs of many of the recombination functions described in E. coli (e.g., recA, recBCD, ruvAB), Red will likely serve to generate the same hyper-rec phenotype when expressed in other (pathogenic) strains of bacteria. This proposal is a test of this hypothesis. This project is designed to generate hyper-recombinogenic strains of Pseudomonas aeruginosa and Mycobacterium tuberculosis by expression of red and phage anti-RecBCD functions in vivo from plasmids, or by replacing the chromosomal recBCD genes with a red-expressing operon. The system can be set up so that the hyper-rec phenotype is transient, resulting in pathogens that are altered only within the gene of interest. This project has the potential to revolutionize the methods of genetic manipulation in microorganisms, leading to faster identification of virulence genes, greater flexibility in the genetic analysis of these genes, and the speedy generation of bacterial mutants for vaccine development. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen

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Project Title: REGULATION OF CYCLIC NUCLEOTIDE METABOLISM Principal Investigator & Institution: Gilman, Alfred G.; Professor of Pharmacology; Pharmacology; University of Texas Sw Med Ctr/Dallas Dallas, Tx 753909105 Timing: Fiscal Year 2001; Project Start 01-JAN-1985; Project End 31-DEC-2003 Summary: Members of a family of guanine nucleotide-binding regulatory proteins (G proteins) are responsible for transmission of information from many membrane-bound receptors for hormones, neurotransmitters, autacoids, and physical stimuli to their intracellular effectors. Although there are several such pathways, the best studied are those for dual (stimulatory and inhibitory) regulation of adenylyl cyclase and for lightstimulated hydrolysis of cyclic GMP in retinal rods and cones. The broad gaol of the research proposed in this application is to elucidate molecular mechanisms of transmembrane signaling in pathways that include such G proteins as crucial regulatory

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elements. Specific aims can be organized with regard to the G protein or effector system to be investigated. Gs is the G protein responsible for stimulation of adenylyl cyclase activity and activation of dihydropyridine-sensitive Ca2+ channels. The alpha subunit of Gs has been synthesized in E. coli and characterized. Large amounts of recombinant Gs alpha have been purified to homogeneity for the purpose of collaborative attempts to crystallize the protein and determine its three dimensional structure. The nature of covalent modifications of Gs alpha thought to be necessary for high-affinity interactions between the G protein and its effectors will also explored. The Gi/Go family of G proteins will be studied as homogeneous products after expression in E. coli. Their basic biochemical properties (e.g., kinetics of guanine nucleotide binding and hydrolysis) will be defined, as will the specificity of their interactions with receptors (e.g., alpha and beta adrenergic) and effectors (e.g., adenylyl cyclase, K+ channels, Ca2+ channels). The specificity and mechanisms of interactions of these proteins with receptors and effectors will also be studied by expression of various mutant Gi alpha and Go alpha subunits in appropriate cultured cell lines. The significance of amino-terminal myristoylation of these alpha subunits will also be investigated. Gz is a newly appreciated G protein with unique structural features. Its biological role is unknown. Gz will be purified from bovine brain and characterized; Gz alpha will also be expressed in E. coli. Biochemical and molecular biological approaches will be taken to elucidate its functions. Newly clone cDNAs that encode individual forms of adenylyl cyclase will be expressed in appropriate cell systems, and the properties of the enzymes that they encode will be determined. Antibodies will be raised to individual forms of the protein. The functional domains of this complex membrane-bound enzyme will be studied. The significance of the "channel- like" topology of adenylyl cyclase will be investigated. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •

Project Title: REPAIR OF CLUSTERED DNA DAMAGES Principal Investigator & Institution: Kow, Yoke W.; Professor; Radiation Oncology; Emory University 1784 North Decatur Road Atlanta, Ga 30322 Timing: Fiscal Year 2002; Project Start 11-JAN-2002; Project End 31-DEC-2005 Summary: (provided by applicant): Ionizing radiation produces a wide spectrum of DNA damages including base and sugar damages, single and double strand breaks, abasic sites, DNA-protein and DNA-DNA crosslinks as well as multiply damage sites(MIDS). Double strand breaks are repaired either by homologous recombination or non-homologous end-joining mechanism. Despite the fact that double strand break is a lethal lesion, lethality induced by ionizing radiation cannot be fully explained by the amount of double strand breaks formed. It was suggested by Ward that a significant amount of cell killing by low LET radiation at biological relevant doses is due to the production of MDS, a cluster of damages within a localized region. There is increasing evidence that MDS are biologically important and might contribute significantly to lethality and mutagenesis induced by ionizing radiation. The long-term goal for this project is to understand the biological consequences of MDS. Two approaches are taken in order to achieve this goal. Aims 1 to 2 are directed to elucidate the in vivo biological consequences of MDS. A yeast shuttle plasmid, pRS413, containing various MDS will be constructed and used to transform E. coli of various repair backgrounds. The lethality conferred by various MDS will be scored by measuring the survival of damaged pRS413 and the mutagenicity of MDS by direct sequencing of the mutant progeny plasmid obtained after transformation. In addition, in vitro processing of these MDS will be studied in Aims 3 and 4. Aim 3 is directed to examine the in vitro processing of DNA containing tandem lesions by E. coli BER enzymes including endonucleases III and VIII,

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formamidopyrimidine N-glycosylase and 5? AP endonucleases from E.coli. The nature of the reaction products and the kinetics of removal for each of the lesions within the MDS will be elucidated. In addition, a complete in vitro analysis of the possible enzymatic steps involved in the repair of tandem lesions will also be performed. Aim 4 is directed to examine whether E. coli DNA binding protein, such as HU protein can mediate the sequential repair of closely opposed lesion. It is believed that a comprehensive study involving in vivo biological and in vitro enzymatic studies will provide significant insight into understanding the biological consequences of MDS, and thus the genotoxic and mutagenic effect of ionizing radiation. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •

Project Title: ROLE OF COMPLEMENT PROTEINS IN E. COLI MENINGITIS Principal Investigator & Institution: Nemani, Prasadarao V.; Children's Hospital Los Angeles 4650 Sunset Blvd Los Angeles, Ca 90027 Timing: Fiscal Year 2002; Project Start 01-APR-2002; Project End 31-MAR-2004 Summary: (provided by applicant): Neonatal E. coli K1 meningitis is the most common serious infection of the central nervous system with unchanged rates of mortality and morbidity. Survivors of this disease suffer a number of complications including mental retardation and speech impairment. Limited knowledge about the pathogenesis and pathophysiology of this disease hampered the efforts to develop new therapeutic strategies for the prevention. For example, most cases of E. coli K1 meningitis occur via hematogenous spread, but it is unclear how the circulating E. coli evades the hostdefense mechanisms. The investigator's studies have shown that outer membrane protein A (OmpA) of E. coli contributes to resistance to serum bactericidal activity. In addition, OmpA interacts with a brain specific 95 kDa receptor for E. coli invasion of the blood-brain barrier (BBB). The E. coli invasion of the BBB was significantly reduced in the presence of adult human serum (AHS) when compared to cord blood serum (CBS) using the investigator's in vitro model of the BBB, the cultured brain microvascular endothelial cells (BMEC). His data further showed that OmpA binds to C4-binding protein, a complement fluid phase regulator, in significant quantities from AHS when compared to CBS. A compelling observation is that the binding of C4-binding protein to OmpA blocked the E. coli invasion of BMEC, suggesting that it is competing with the OmpA-receptor. The investigator hypothesized that binding of C4BP to OmpA blokcs the E. coli invasion of BMEC and that low levlels of C4BP may contribute to the susceptibility of neonates to E. coli meningitis. He will pursue this hypothesis by study of the following specific aims. 1. To determine the binding site of C4BP on OmpA that blocks E. coli invasion of BMEC, and 2. To assess the effect of anti-OmpA antibody, OmpA-peptides, and C4BP-peptides on E. coli invasion of BMEC in the newborn rat model of hematogenous meningitis. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen

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Project Title: ROLE OF EXPRESSION

SIGMA

FACOTRS IN

HETEROLOGOUS GENE

Principal Investigator & Institution: Sabree, Zakee L.; Plant Pathology; University of Wisconsin Madison 750 University Ave Madison, Wi 53706 Timing: Fiscal Year 2003; Project Start 01-SEP-2003; Project End 31-AUG-2008 Summary: (provided by applicant): Soil microbes are ubiquitous, diverse and impact global nutrient cycling and biogeochemical structuring, yet much of our current understanding is built largely on what is known about culturable ebacteria, which

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comprise < 1% of the total microbial diversity. Advances in culturing methods and culture-independent approaches are essential to gain a more complete understanding of the microbial world. Our laboratories have developed metagenomics, which is a cultureindependent approach to identifying genes and activities from soil microbes, thereby broadening our understanding of the uncultured microbes. Functional metagenomics relies on heterologous expression of foreign genes in Escherichia coli and other host species, and therefore the role of transcriptional factors in heterologous expression is integral to metagenomic analysis. My overall hypothesis is that introduction and manipulation of sigma factors can expand the range of genes from cultured and uncultured bacteria expressed in E. coli. My sub-hypotheses to be tested are: 1) Acidobacterium capsulatum RpoD will increase expression of Acidobacterium genes in E. coli 2) Induction of E. coli heat shock sigma factor (RpoH) will increase the likelihood of identifying tellurite resistance genes from Rhodobacter sphaeroides and uncultured bacteria The goal of this research is to establish the influence of sigma factors on heterologous gene expression. My research will contribute to our understanding of sigma factors and gene regulation and resulting in a novel functional characterization of genes from cultured and uncultured bacteria. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •

Project Title: ROLE OF TRAJ IN NEONATAL E. COLI SEPSIS AND MENINGITIS Principal Investigator & Institution: Badger, Julie L.; Children's Hospital Los Angeles 4650 Sunset Blvd Los Angeles, Ca 90027 Timing: Fiscal Year 2003; Project Start 01-APR-2003; Project End 31-MAR-2008 Summary: (provided by applicant): Despite the use of modern therapeutics and diagnostic measures, neonatal bacterial sepsis and meningitis continues to be a disease with unacceptable rates of morbidity and mortality. The fatality rate of this disease is 1575 percent; furthermore, approximately 50 percent of meningitis survivors have significant neurological and developmental abnormalities. The primary, route of infection for E. coli K1 (the most common causative agent of gram-negative meningitis) is oral. Following intestinal colonization, bacteria translocate through the GI tract to extra-intestinal sites of mesenteric lymph nodes (MLN), liver, spleen, and the blood. E. coli K1 then multiply systemically within the bloodstream reaching a necessary threshold of bacteremia to gain access to the central nervous system (CNS). Recently we identified an E. coli K1 plasmid-encoded blood-brain barrier (BBB) invasion gene, traJ, with homology to traJ of various F-like plasmid tra operons. Our preliminary data indicate that the traJ mutation specifically attenuates dissemination from the MLN to the liver, spleen, blood, and the CNS in the neonatal rat. In addition, although animals orally infected with the traJ mutant demonstrated a decrease or no recoverable bacteria in the liver or spleen, these tissues showed a significant inflammatory response. In vitro studies determined that the traJ mutant is taken-up less by macrophages and shows a loss of a 55 kDa-secreted protein. The central hypothesis of this application is that TraJ controls the expression of a set of genes whose products (i.e., 55 kDa secreted protein) are involved in E. coli K1 dissemination, systemic infection and crossing the BBB, and these events within the disease process occur via TraJ-dependent interactions with professional phagocytes. The following proposed experiments are designed to test and substantiate our hypotheses. We aim to 1) Elucidate the genetic and molecular characteristics of the traJ region and plasmid, evaluate the ability of the endogenous plasmid to self-transfer, and determine the potential role of the traJ-containing plasmid in E. coli K1 neonatal rat virulence, 2) Evaluate the function of the TraJ-regulated proteins (i.e., 55 kDa-secreted protein) in E. coli K1 systemic dissemination and

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meningitis, and 3) Determine the mechanism of TraJ-dependent host inflammatory response in the neonatal rat. Improved knowledge of molecular mechanisms for early systemic dissemination and the exact interplay of the host inflammatory response during these events will assist in achieving our long-term goal of identifying novel rational approaches to development of new treatments and preventive strategies for E. coli K1 sepsis and meningitis. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •

Project Title: SHIGA TOXIN ENCODING PHAGE AND INTESTINAL E.COLI Principal Investigator & Institution: Weiss, Alison A.; Professor; Molecular Genetics, Biochemistry & Microbiology; University of Cincinnati 2624 Clifton Ave Cincinnati, Oh 45221 Timing: Fiscal Year 2003; Project Start 15-FEB-2003; Project End 31-JAN-2005 Summary: (provided by applicant): Shiga toxin-producing Escherichia coli, including O157:H7, are emerging pathogens of major importance. Bacterial colonization is associated with intestinal disturbances; however, the severe, potentially fatal symptoms of bloody diarrhea (hemorrhagic colitis) and destruction of the kidney leading to hemolytic uremic syndrome (HUS) are due to a bacterial toxin, Shiga toxin. The genes for Shiga toxin are encoded by a temperate bacteriophage in the late gene operon. Shiga toxin is expressed when the phage lytic cycle is induced, along with the genes necessary for production of viral particles and bacterial lysis. Phage-mediated bacterial lysis is necessary for toxin secretion. The viral particles produced during infection with the pathogenic O157:H7 can infect the nonpathogenic intestinal E. coli. When this occurs, the previously harmless E. coli will produce Shiga toxin and amplify the pathogenic process. Our preliminary data suggest that the Shiga toxin production by intestinal flora can be substantial and that severe, possibly life-threatening disease is more likely to occur in individuals whose intestinal flora can be infected by the Shiga toxin phage. In contrast, individuals with intestinal flora that are resistant to the Shiga toxin phage will be protected from severe disease. Currently, it is difficult to prevent disease by E. coli O157:H7 since the infectious dose is very low, and antibiotic treatment, instead of being beneficial, can enhance progression to fatal disease. We propose to develop methods to convert the intestinal flora to phage-resistance as a therapeutic approach to controlling disease caused by Shiga toxin-producing pathogens. This is especially important since there is no treatment, other than supportive care, once disease has developed. The specific aims of this application are to: 1) Characterize Shiga toxin production by clinical isolates of O157:H7 in the presence of susceptible or resistant human intestinal E. coli; and 2) Develop methods to convert intestinal flora to phage resistance using a mouse model of disease. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen

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Project Title: SIGMA E-DEPENDENT HEAT SHOCK RESPONSE OF E COLI Principal Investigator & Institution: Missiakas, Dominique M.; Biochem and Molecular Biology; University of Chicago 5801 S Ellis Ave Chicago, Il 60637 Timing: Fiscal Year 2001; Project Start 01-AUG-1998; Project End 31-JUL-2003 Summary: Genetic and biochemical analyses have revealed the presence in E. coli of two distinct sets of genes that respond to the accumulation of misfolded or damaged polypeptide chains resulting from a heat shock. The classical heat shock response is triggered by protein misfolding in the cytoplasm and is mediated by the RNA polymerase minor sigma factor, sigma32 (the product of rpoH). A second heat shock

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response, mediated by a second minor sigma factor, sigmaE (the product of rpoE), is triggered by the accumulation of misfolded proteins in the extracytoplasmic space (ie., the periplasm and outer membrane compartments of E. coli). This proposal investigates two major questions: (1) How are misfolded proteins detected in the periplasm? (2) How does detection of misfolded proteins trigger sigmaE-dependent transcription of specific heat shock genes, including rpoH)? These questions will be addressed by examining the roles of four proteins, sigmaE, RseA, RseB, and RseC. Genes encoding the last three of these proteins were identified by mutational studies conducted by the PI, which permitted the development of a model in which contact with misfolded proteins in the periplasm triggers a conformational change in the transmembrane protein RseA, relaxing its inhibitory effect on cytoplasmic sigmaE. These interactions are modulated positively and negatively by RseB and RseC. The proposal is designed to use a combination of genetic and biochemical experiments to elucidate the precise function of these proteins. The goals are to determine whether RseA or RseB is the actual sensor of misfolded proteins and to determine how the signal is relayed to effect the release of sigmaE from RseA. The role of sigmaE-dependent operons in the physiological response to the accumulation of misfolded polypeptide will also be investigated. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •

Project Title: STRUCTURAL /FUNCTIONAL ANALYSIS OF SFID REGION OF E. COI Principal Investigator & Institution: Mcpartland, Ann A.; California State University Hayward Hayward, Ca 94542 Timing: Fiscal Year 2001; Project Start 01-SEP-1993; Project End 31-MAY-2005 Description (provided by applicant): The overall aim of this project is to probe the mechanisms regulating cell division in Escherichia coli. In virtually all cell types, cell division is strictly controlled; periods of cell growth, DNA duplication and chromosome partitioning always precede cytokinesis. Yet the mechanisms by which these processes are coordinated are poorly understood. E. coli provides a relatively simple model system for studying cell division. An understanding of how division is regulated should eventually lead to an explanation of how DNA replication, chromosome partitioning and cell division are coordinated. This information could prove valuable in the search for ways of blocking uncontrolled growth and division in eukaryotic cells. The sfiD gene appears to play a role in regulating cell division in E. coli. Insertions of the IS1 transposon into an adjacent, upstream site confer mutant phenotypes that can be complemented by the sfiD+ gene. These include normal division in the presence of the inducible division inhibitors SulA and SfiC, cold sensitivity for growth and sensitivity to beta-lactam antibiotics. A number of the proposed experiments are directed toward analysis of the transcription patterns in the sfiD region. These include the use of RT-PCR and primer extension to define the sfiD mRNA(s) in normal and mutant cells. The effect of deleting potential regulatory sites on transcription initiated at the sfiD promoter will also be examined. In other experiments the SfiD protein will be purified and its structure, cellular location and stability compared in normal and mutant cells. As a means of understanding how upstream IS1 insertions alter sfiD, the sequence changes in revertants carrying second site mutations linked to sfiD will be determined. Other unlinked second site mutations will be mapped with a view toward identifying proteins that interact with SfiD. Placement of the division complex will be examined in revertants exhibiting altered morphology. Finally, the penicillin binding proteins will be compared in normal and mutant cells. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen

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Project Title: STRUCTURAL STUDIES OF DNA REPAIR PROTEINS Principal Investigator & Institution: Ellenberger, Tom E.; Professor; Biological Chem & Molecular Pharm; Harvard University (Medical School) Medical School Campus Boston, Ma 02115 Timing: Fiscal Year 2001; Project Start 01-MAY-1995; Project End 31-DEC-2002 Summary: Our genetic integrity is assured by the precise repair of DNA damage caused by chemical mutagens, ionizing radiation, and the spontaneous hydrolytic decay of DNA bases. Defects in DNA repair have been linked to a growing repair of inherited diseases of humans. The efficient repair of DNA damage in neoplastic cells poses an obstacle to the effective chemotherapy of cancer with alkylating agents. We are studying the structures of several DNA base excision repair proteins by x-ray crystallographic methods in order to understand how these enzymes located damaged bases in DNA and cleave the N-glycosylic bond, releasing the damaged base from DNA. Several DNA N-glycosylases from E. coli and humans that recognize alkylation-damaged DNA have been crystallized in complexes with specific DNA substrates and inhibitors. Crystal structures of these complexes are being determined by multiple isomorphous replacement and multiple wavelength anomalous diffraction experiments. These repair enzymes have different specificities for the types of alkylated bases that they excise from DNA. Broadly specific enzymes like the E. coli AlkA protein efficiently remove many types of alkylated purines with little regard for the shapes of positions of adducts on the purine base. We previously determined a 1.8 A crystal structure of unliganded AlkA and discovered an active site pocket containing many aromatic residues. This electronrich environment may serve as a binding site for electron- deficient, alkylated bases that are "flipped out" of the DNA helix prior to cleavage of the N-glycosyl bond. This hypothesis will be addressed by crystal structures of AlkA complexed to an inhibitory DNA containing a modified a basic site and of an inactive AlkA mutant complexed to a alkylated purine in DNA. The human alkyladenine DNA glycosylase (AAG) is a functional analog of AlkA that bears no sequence resemblance to AlkA. The crystal structure of an AAG-DNA complex is being determined. Conserved features of the active sites of AAG and AlkA are likely to reflect a common strategy for locating damages bases, exposing them to the enzyme active site, and catalyzing the scission of the N-glycosyl bond. In contrast to AlkA and AAG, the E. coli Tag glycosylase is highly selective for the removal of 3-methyladenine from DNA. Crystallographic studies of Tag will address the structural basis of Tag's strict substrate preference and perhaps reveal a different catalytic strategy. Functional studies of AlkA, AAG, and Tag glycosylases are being performed to identify residues with important roles in DNA binding, baseflipping, and enzymatic catalysis. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen

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Project Title: STRUCTURAL STUDIES OF EXORIBONUCLEASES Principal Investigator & Institution: Malhotra, Arun; Biochem and Molecular Biology; University of Miami-Medical Box 248293 Coral Gables, Fl 33124 Timing: Fiscal Year 2003; Project Start 30-SEP-2003; Project End 31-AUG-2008 Summary: (provided by applicant): Ribonucleases (RNases) play a central role in a number of vital RNA cellular processes in all living cells. One of these processes is mRNA degradation, which is an important mechanism for post-transcriptional control of gene expression. RNases are also required for maturation and turnover of structural RNAs. E. coli has served as a model system for understanding the role of ribonucleases in cellular RNA metabolism, and eight distinct exoribonucleases have been identified in

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this bacterium. Of these, three (RNase T, Rnase D, and oligoribonuclease) are members of a larger exonuclease superfamily that includes the proof-reading domains of DNA polymerases. These three proteins share similar sequence motifs and have been dubbed the DEDD family exoribonucleases. However, functionally these exoribonuclease are quite distinct. We have initiated structural studies of this family of exoribonucleases, in collaboration with the laboratory of Dr. Murray Deutscher at the University of Miami, to structurally characterize these proteins. The structure of oligoribonuclease has been solved and we have diffraction quality crystals of RNase T. Specifically, we propose to: 1. Initiate detailed structure-function studies of oligoribonuclease to better understand its active site, metal requirements, and dimeric state. We also propose to look for differences between the prokaryotic and eukaryotic forms of this enzyme, by obtaining the structure of the human homologue of oligoribonuclease. 2. Optimize the crystals obtained for RNase T, and derive its atomic structure. 3. Determine the atomic structure of RNase D. 4. Understand the similarities and differences between these three enzymes in terms of substrate specificity, quarternary structure, metal requirements and catalytic mechanism, to better characterize this family of enzymes. The long term goals of this research are to understand the structures and mechanisms of action of all the exoribonucleases in a single organism (E. coli); these studies will complement a parallel study to completely determine and characterize the physiological role of all the exoribonucleases in E. coli, now underway in the Deutscher laboratory. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •

Project Title: STRUCTURAL STUDIES OF METHYL CYCLE ENZYMES Principal Investigator & Institution: Takusagawa, Fusao; Associate Professor; Molecular Biosciences; University of Kansas Lawrence Lawrence, Ks 66045 Timing: Fiscal Year 2001; Project Start 01-APR-1988; Project End 31-MAR-2004 Summary: Methylation reactions mediated by S-adenosylmethlonine (AdoMet) are increasingly being recognized as significant control factors in the regulation of a variety of cellular functions. Methylation of nucleic acids is known to have regulatory effects on DNA replication and transcription, and RNA translation. Protein methylation is involved in the regulation of a variety of metabolic processes such as bacterial chemotaxis, sperm mobility, release of neurotransmitters and possibly certain enzymatic activities. AdoMet is also the methyl donor for a vast number of small molecules (e.g., the biosynthesis and/or metabolism of various catechoiamine neurotransmitters). We have studied the structures and functions of enzymes involved in the methyl cycle reactions. A relatively large conformational change has been observed in the enzyme structures upon the binding of substrate or the leaving of product from the active site. In this grant period, Dr. Takusagawa will characterize the dynamic structures as well as the catalytic mechanisms of the following enzymes by X-ray diffraction method. Sadenosylm ethionine synthetase from human, rat, Methanococcus jannaschii, and E. coli. Glycline N-methyltransferase and guanidinoacetate methyltransferase from rat liver. S-adenosylhomocysteine hydrolase from rat liver and Alcaligenes faecalis. Sadenosylmethionine decarboxylase from E. coli. N10-formyl-tetrahydrofolate synthetase from Clostridium cylindrosporum. Serine dehydratase from rat liver. For a long-term objective, we would like to design specific inhibitors of these enzymes in order to develop chemotherapeutic agents using the active site geometries and the catalytic mechanisms of the enzymes gained in this project. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen

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Project Title: STRUCTURE AND RELATIONS OF PROTEINS AND NUCLEIC ACIDS Principal Investigator & Institution: Von Hippel, Peter H.; Professor; Institute of Molecular Biology; University of Oregon Eugene, or 97403 Timing: Fiscal Year 2002; Project Start 01-JAN-1978; Project End 31-DEC-2005 Summary: In this grant application we describe plans to continue our ongoing studies of the molecular mechanisms and regulation of the transcription complex of E. coli. We will focus, in particular, on how the complex is regulated by transcription factors, building on the recent major progress that has greatly increased our understanding both of many aspects of the structure of the complex, as well as of the thermodynamics and kinetics of the control of the reactions that lead to transcript initiation, elongation, editing, and termination. This later progress, in particular, makes it possible for us to begin to develop quantitative insight into the changes that the binding of transcription factors must bring about to (e.g.) redirect the transcription process from elongation to transcript editing or termination. During the next reporting period our Specific Aims will be: (i) to continue our studies of the mechanisms whereby the N protein-dependent antitermination system of phage lambda controls the transcription termination efficiency of E. coli RNA polymerase at intrinsic and rho-dependent terminators; (ii) to carry out fundamental studies of RNA flexibility and looping as a component of transcription regulation; (iii) to elucidate the role of specific RNA sequences and E. coli host factors in regulating the "range" and specificity of "full" transcription factor complexes involved in N-dependent antitermination; (iv) to determine the detailed mechanism of action of E. coli transcription termination factor rho at rho-dependent terminators, and to study the roles of "coupling factors" in regulating the efficiency of the rho-dependent termination process; (v) to examine the interconversion of the various forms of the E. coli transcription elongation complex that lead, respectively, to elongation, editing, and termination, as well as to use rho as a probe of these "functional states"; and (vi) to perform theoretical and modeling studies of the assembly and stability of functional complexes of transcription factors to better understand how these complexes assemble, and how the components interact to build a stable "macromolecular machine". In terms of their significance for biomedical research, these studies will serve as molecular models for the function and control of the analogous DNA-dependent RNA transcription systems of higher organisms, and may help reveal how these controls can go awry in cancer and other diseases of inappropriate gene expression. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen

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Project Title: STRUCTURE, FUNCTION AND REGULATION OF PRIMASE Principal Investigator & Institution: Godson, G N.; Biochemistry; New York University School of Medicine 550 1St Ave New York, Ny 10016 Timing: Fiscal Year 2001; Project Start 01-AUG-1986; Project End 31-MAR-2004 Summary: DNA replication cannot take place without active primase. The broad longterm goal of this proposal is to learn enough about primase to develop it as a target to inhibit DNA replication in cancer cells. This proposal continues our studies of the structure, function and mechanism of primer RNA synthesis by E. coli primase and extends our studies to human primase. In the revised proposal, Specific Aim #1 is to study mechanism of movement of E. coli primase on DNA template. A hypothesis of a periodic, punctuated synthesis of pRNA by E. coli primase will be tested by measuring the processivity of primase and dissociation and rebinding of primase to the template

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after each step of synthesis (10/11 nt, 21/22 nt and 24/25 nt). A primase elongation mutant will be used for these experiments. Specific Aim #2 is to analyze the active center of pRNA synthesis of E. coli primase. We will use Fe2+ cleavage and site-directed mutagenesis to localize amino acids that bind Mg2+ at the catalytic center and Zn2+ at the zinc finger. The DNA template binding sites will be analyzed using template oligonucleotides containing UV photoreactive nucleotides incorporated in specific positions. The exit pathway of the growing primer RNA chain will be similarly mapped by using photoreactive oligonucleotide primers. Changes in the conformation of primase during pRNA synthesis will be analyzed. In Specific Aim #3, we will continue to study the role of SSB in pRNA synthesis. A primase/SSB physical interaction will be trapped by biochemical methods. The yeast two-hybrid system will be used to further analyze primase/SSB interaction. Interaction sites on both primase and SSB will be identified. In Specific Aim #4, we will establish the domain structure of the human primase P49 and 58 subunits of DNA polymerase alpha. The active center of this twoprotein system will be identified by ATP affinity cross-linking technique plus chemical cleavage. The function of these regions will be explored by site-directed mutagenesis. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •

Project Title: STRUCTURE/FUNCTION STUDIES OF TYPE I TOPOISOMERASES Principal Investigator & Institution: Mondragon, Alfonso; Professor; Biochem/Molecular & Cell Biol; Northwestern University 633 Clark St Evanston, Il 60208 Timing: Fiscal Year 2001; Project Start 01-AUG-1994; Project End 31-JUL-2002 Summary: (Adapted from applicant's abstract): DNA topoisomerases are enzymes that change the topological state of DNA. They are involved in several crucial cellular processes such as replication, transcription, chromosome segregation, and chromosome condensation. More important, they have become the focus of study as a target of novel anti-bacterial and chemotherapeutic agents. The understanding of the structure of topoisomerases promises not only to further our understanding of proteins that interact with DNA and modify its topological properties, but also to provide important information to aid in the design of new therapeutic agents. The long term goal of this proposal is to understand the mechanism of action of type I topoisomerases in atomic detail. Two type I topoisomerases have been identified in Escherichia coli, DNA topoisomerase I and III. The investigators have solved the structure of the two enzymes and their structures suggest an enzyme-bridged mechanism that may apply to all type 1-5' topoisomerases and that has interesting parallelism with the mechanism of type II topoisomerases. The investigators have proposed a detailed mechanism for the cleavage/religation reaction that they are currently testing by mutagenesis. Other studies have allowed identification of two putative DNA binding sites by protein crystallography. The specific aims for this proposal are: i) to refine the structure of the intact and active E. coli DNA topoisomerase III to high resolution (2.4 A or better), ii) to study the interactions of E. coli DNA topoisomerases I and III with DNA, iii) to identify and characterize the structural and chemical determinants of catalytic activity and to elucidate their specific role in the reaction, and iv) to characterize and solve the structure of different domains of E. coli DNA topoisomerase I. The work is based on a combination of molecular biology and biochemical methods to produce and characterize the proteins that we require for our work, and x-ray crystallography to solve their structures to high resolution. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen

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Project Title: T-EVEN PHAGES FOR FOOD-CHAIN BIOCONTROL OF E.COLI 0157 Principal Investigator & Institution: Kutter, Elizabeth M.; Professor; Biophysics; Evergreen State College 2700 Evergreen Pky Nw Olympia, Wa 98505 Timing: Fiscal Year 2001; Project Start 01-AUG-2001; Project End 31-JUL-2003 Summary: The long-term objectives of this proposal are (1) to investigate the dynamicsand physiology of T-even phage replication under conditions relevant to the natural environment and to potential therapeutic applications, i. e. during anaerobic respirative and fermentative growth of the host, (2) to identify and characterize T-even phages capable of infecting E. coil 0157:147 anaerobically and use appropriatelydesigned mixed-culture fermenters to assess the potential for use of these phages as a means of reducing the 0157:147 load in the guts of cattle, and (3) t'dentify regimes for efficiently producing and effectively administering the chosen phages. Preliminary experiments have identified 12 T-even phages that can infect 0157 and have shown that some T-even phages can infect E. coli growing under conditions of anaerobic respiration and/or fermentation, but the process is substantially different than during aerobic infection, and also differs between fermentation and respiration, between different host strains and between different related phages. Studies will include effects of available nutrients, electron acceptors, and pH and will determine various phage growth parameters --adsorption efficiency, lysis time and lysis inhibition patterns, intracellular phage production, and burst size. This data will be used to set up continuous-flow anaerobic fermentors simulating the bovine rumen and the colon environment to model in the laboratory the population dynamics of the relationship between predator (phage) and prey (including nonpathogenic derivatives of E. coli 0157:147), facilitating selection of the most promising phages and diets for treatment and exploration of the parameters of phage-host interaction as they are affected by conditions and by the presence of other rumen and colon bacteria. Phage will be prepared and supplied to Dr. Todd Callaway of the USDA, who will extend these studies to pathogenic strains and to in vivo studies in cattle. Such experiments are very well suited to work by students in our undergraduate setting, leading to a firm foundation in understanding microbial ecology and physiology, general microbial and anaerobic techniques, proteomics, and experimental design, along with the satisfaction of contributing significant new research results. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen

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Project Title: THE EVOLUTION OF SPECIALISTS AND GENERALISTS Principal Investigator & Institution: Dean, Antony M.; Biotechnology Institute; University of Minnesota Twin Cities 200 Oak Street Se Minneapolis, Mn 554552070 Timing: Fiscal Year 2001; Project Start 01-AUG-2001; Project End 31-JUL-2005 Summary: (provided by applicant): An understanding of microbial evolution is seen as increasingly important to an understanding of disease and the design of effective therapies. As such, this proposal aims to investigate the genetic, biochemical and physiological mechanisms underpinning evolution in microbes. Of particular interest is an assessment of the degree to which adaptive evolution is predictable. For if evolution is predictable, more efficacious therapies might be designed, undesirable evolutionary outcomes (e.g. multi-drug resistance) avoided, the origin and evolution of epidemics better understood, and as a consequence better strategies in public health implemented. An understanding of microbial evolution remains elusive because studies are either overwhelmed by complexity or reduced to the trivially predictable. However, the lactose pathway of E. coli represents a unique balance between complexity and simplicity. It is sufficiently complex that a diversity of adaptive responses - specialists,

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generalists, commensals - arise, yet it is sufficiently simple that each can be analyzed in detail. This balance between complexity and simplicity enables the predictability of adaptive evolution to be investigated. Strong frequency dependent selection maintains variation in lactose operons of E. coli during competition for limiting mixtures of galactosides. Long-term chemostat competition experiments reveal that new adaptations may intensify the frequency dependence or they may diminish it to the point whereby the polymorphism is lost. Balanced polymorphisms can arise from within a single clone. The evolution of specialists towards particular galactosides promotes polymorphism and suggests that trade-offs at the molecular level govern the evolution of diversity. The evolution of generalists (strains capable of efficiently metabolizing all galactosides) destabilizes polymorphisms and demonstrates that trade-offs are not inevitable. The genetic, physiological and biochemical mechanisms that promote the appearance, and loss, of these polymorphisms will be determined. Replicate experiments will determine the predictability of evolutionary outcomes. Evolved strains will be analyzed to determine the population level interactions that result in stabilizing or destabilizing the polymorphisms. Biochemical studies will determine the physiological basis for the evolution of specialists and generalists, and to determine the molecular causes of tradeoils. Mutational changes will be sequenced to determine the predictably of evolution at the molecular level. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •

Project Title: TRNA: STUDIES OF PRECURSORS, MUTANTS AND FUNCTIONS Principal Investigator & Institution: Altman, Sidney; Professor; Molecular and Cellular Physio; Yale University 47 College Street, Suite 203 New Haven, Ct 065208047 Timing: Fiscal Year 2001; Project Start 01-JUL-1981; Project End 31-MAR-2004 Summary: (from the applicant's abstract): The biogenesis of tRNA from primary gene transcripts to their final functional form in E. coli, yeast and human cells will be investigated and, in particular, the function of Rnase P, a ribonucleoprotein essential for the processing of the 5' termini of tRNAs, will be examined in detail. The function in vivo of mutants in both subunits of Rnase P from E. coli will be examined by complementation in backgrounds mutant for either the rnpA or rnpB genes. These experiments will verify the results of experiments in vitro in which the function of mutants in both subunits of the enzyme and the substrate have been made and assayed based on their proposed location in a three dimensional model of the RNA subunit of Rnase P and the crystal structure of the protein subunit of Rnase P from B. subtilis. Cross-linking experiments with substrates and enzymatic subunits will also be used to test aspects of the structural models and theories about enzyme-substrate interactions. Genetic methods will be used to assay both RNA-protein interactions in Rnase P and to search for new substrates for RNAse P in E. coli and S. cerevisiae. Characterization of the protein subunits of Rnase P from both yeast and human cells will be completed. Particular subunits, especially from the human enzyme, will be tagged with antigenic and fluorescent markers to facilitate both the purification of the enzyme complexes and studies of the localization of the protein subunits in cells and tissue culture. Reconstitution of the enzyme from isolated subunits will be attempted to facilitate functional studies of individual mutated subunits. Inactivation of in vivo of genes coding for drug resistance in bacteria, for regulation of viral function in a herpes virus in mammalian cells, and of the protein subunit of Rnase P in bacteria will be pursued using the concerted action of small, custom designed RNAs called external guide sequences (EGS) and Rnase P. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen

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E-Journals: PubMed Central3 PubMed Central (PMC) is a digital archive of life sciences journal literature developed and managed by the National Center for Biotechnology Information (NCBI) at the U.S. National Library of Medicine (NLM).4 Access to this growing archive of e-journals is free and unrestricted.5 To search, go to http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=Pmc, and type “E. coli” (or synonyms) into the search box. This search gives you access to full-text articles. The following is a sample of items found for E. coli in the PubMed Central database: •

[beta]-Lactamases in Ampicillin-Resistant Escherichia coli Isolates from Foods, Humans, and Healthy Animals. by Brinas L, Zarazaga M, Saenz Y, Ruiz-Larrea F, Torres C.; 2002 Oct; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=128764

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[minus sign]11 Mutation in the ampC Promoter Increasing Resistance to [beta]Lactams in a Clinical Escherichia coli Strain. by Corvec S, Caroff N, Espaze E, Marraillac J, Reynaud A.; 2002 Oct; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=128767

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2-Hydroxy-dATP is incorporated opposite G by Escherichia coli DNA polymerase III resulting in high mutagenicity. by Kamiya H, Kasai H.; 2000 Apr 1; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=102799

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A Localized Adherence-Like Pattern as a Second Pattern of Adherence of Classic Enteropathogenic Escherichia coli to HEp-2 Cells That Is Associated with Infantile Diarrhea. by Scaletsky IC, Pedroso MZ, Oliva CA, Carvalho RL, Morais MB, FagundesNeto U.; 1999 Jul; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=116525

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A Role for the umuDC Gene Products of Escherichia coli in Increasing Resistance to DNA Damage in Stationary Phase by Inhibiting the Transition to Exponential Growth. by Murli S, Opperman T, Smith BT, Walker GC.; 2000 Feb 15; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=94390

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A stationary phase protein in Escherichia coli with binding activity to the major [sigma] subunit of RNA polymerase. by Jishage M, Ishihama A.; 1998 Apr 28; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=20194

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Acetate and Formate Stress: Opposite Responses in the Proteome of Escherichia coli. by Kirkpatrick C, Maurer LM, Oyelakin NE, Yoncheva YN, Maurer R, Slonczewski JL.; 2001 Nov 1; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=100143

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Acetate Metabolism in a pta Mutant of Escherichia coli W3110: Importance of Maintaining Acetyl Coenzyme A Flux for Growth and Survival. by Chang DE, Shin S, Rhee JS, Pan JG.; 1999 Nov 1; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=94129

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Adapted from the National Library of Medicine: http://www.pubmedcentral.nih.gov/about/intro.html.

With PubMed Central, NCBI is taking the lead in preservation and maintenance of open access to electronic literature, just as NLM has done for decades with printed biomedical literature. PubMed Central aims to become a world-class library of the digital age. 5 The value of PubMed Central, in addition to its role as an archive, lies in the availability of data from diverse sources stored in a common format in a single repository. Many journals already have online publishing operations, and there is a growing tendency to publish material online only, to the exclusion of print.

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Acquisition of the rfb-gnd Cluster in Evolution of Escherichia coli O55 and O157. by Tarr PI, Schoening LM, Yea YL, Ward TR, Jelacic S, Whittam TS.; 2000 Nov 1; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=94755

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Activation of Multiple Antibiotic Resistance in Uropathogenic Escherichia coli Strains by Aryloxoalcanoic Acid Compounds. by Balague C, Vescovi EG.; 2001 Jun; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=90551

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Active-Site Residues of Escherichia coli DNA Gyrase Required in Coupling ATP Hydrolysis to DNA Supercoiling and Amino Acid Substitutions Leading to Novobiocin Resistance. by Gross CH, Parsons JD, Grossman TH, Charifson PS, Bellon S, Jernee J, Dwyer M, Chambers SP, Markland W, Botfield M, Raybuck SA.; 2003 Mar; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=149296

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Acylation of Escherichia coli Hemolysin: A Unique Protein Lipidation Mechanism Underlying Toxin Function. by Stanley P, Koronakis V, Hughes C.; 1998 Jun; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=98917

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Adaptation of Escherichia coli to the Bovine Mammary Gland. by Bradley AJ, Green MJ.; 2001 May; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=88036

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Adherent Invasive Escherichia coli Strains from Patients with Crohn's Disease Survive and Replicate within Macrophages without Inducing Host Cell Death. by Glasser AL, Boudeau J, Barnich N, Perruchot MH, Colombel JF, Darfeuille-Michaud A.; 2001 Sep; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=98666

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Adhesion of Type 1-Fimbriated Escherichia coli to Abiotic Surfaces Leads to Altered Composition of Outer Membrane Proteins. by Otto K, Norbeck J, Larsson T, Karlsson KA, Hermansson M.; 2001 Apr 15; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=95160

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Aerobic inactivation of fumarate reductase from Escherichia coli by mutation of the [3Fe-4S]-quinone binding domain. by Cecchini G, Sices H, Schroder I, Gunsalus RP.; 1995 Aug; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&rendertype=abstr act&artid=177221

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Afa/Dr Diffusely Adhering Escherichia coli Infection in T84 Cell Monolayers Induces Increased Neutrophil Transepithelial Migration, Which in Turn Promotes CytokineDependent Upregulation of Decay-Accelerating Factor (CD55), the Receptor for Afa/Dr Adhesins. by Betis F, Brest P, Hofman V, Guignot J, Kansau I, Rossi B, Servin A, Hofman P.; 2003 Apr; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=152057

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Aggregative adherence fimbria II, a second fimbrial antigen mediating aggregative adherence in enteroaggregative Escherichia coli. by Czeczulin JR, Balepur S, Hicks S, Phillips A, Hall R, Kothary MH, Navarro-Garcia F, Nataro JP.; 1997 Oct; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&rendertype=abstr act&artid=175595

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Alterations in Protein Expression Caused by the hha Mutation in Escherichia coli: Influence of Growth Medium Osmolarity. by Balsalobre C, Johansson J, Uhlin BE, Juarez A, Munoa FJ.; 1999 May 15; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=93755

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AmpC and AmpH, proteins related to the class C beta-lactamases, bind penicillin and contribute to the normal morphology of Escherichia coli. by Henderson TA, Young KD, Denome SA, Elf PK.; 1997 Oct; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&rendertype=abstr act&artid=179516

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An ABC Transporter System of Yersinia pestis Allows Utilization of Chelated Iron by Escherichia coli SAB11. by Bearden SW, Staggs TM, Perry RD.; 1998 Mar 1; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=107000

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An Automated Fluorescent PCR Method for Detection of Shiga Toxin-Producing Escherichia coli in Foods. by Chen S, Xu R, Yee A, Wu KY, Wang CN, Read S, De Grandis SA.; 1998 Nov; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=106629

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An Escherichia coli System Expressing Human Deoxyribonucleoside Salvage Enzymes for Evaluation of Potential Antiproliferative Nucleoside Analogs. by Wang J, Neuhard J, Eriksson S.; 1998 Oct; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=105907

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An Improved Enrichment Broth for Isolation of Escherichia coli O157, with Specific Reference to Starved Cells, from Radish Sprouts. by Sata S, Fujisawa T, Osawa R, Iguchi A, Yamai S, Shimada T.; 2003 Mar; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=150063

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Anaerobic Expression of Escherichia coli Succinate Dehydrogenase: Functional Replacement of Fumarate Reductase in the Respiratory Chain during Anaerobic Growth. by Maklashina E, Berthold DA, Cecchini G.; 1998 Nov 15; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=107675

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Analysis of cell size and DNA content in exponentially growing and stationary-phase batch cultures of Escherichia coli. by Akerlund T, Nordstrom K, Bernander R.; 1995 Dec; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&rendertype=abstr act&artid=177544

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Analysis of Escherichia coli O157:H7 Survival in Ovine or Bovine Manure and Manure Slurry. by Kudva IT, Blanch K, Hovde CJ.; 1998 Sep; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=106705

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Analysis of the F Antigen-Specific papA Alleles of Extraintestinal Pathogenic Escherichia coli Using a Novel Multiplex PCR-Based Assay. by Johnson JR, Stell AL, Scheutz F, O'Bryan TT, Russo TA, Carlino UB, Fasching C, Kavle J, Van Dijk L, Gaastra W.; 2000 Mar; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=97319

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Antibacterial Activity Evaluation of Microcin J25 against Diarrheagenic Escherichia coli. by Sable S, Pons AM, Gendron-Gaillard S, Cottenceau G.; 2000 Oct; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=92352

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Antibiotic Resistance, Virulence Gene, and Molecular Profiles of Shiga ToxinProducing Escherichia coli Isolates from Diverse Sources in Calcutta, India. by Khan A, Das SC, Ramamurthy T, Sikdar A, Khanam J, Yamasaki S, Takeda Y, Nair GB.; 2002 Jun; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=130831

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Antibiotic-Resistant Cell-Detaching Escherichia coli Strains from Nigerian Children. by Okeke IN, Steinruck H, Kanack KJ, Elliott SJ, Sundstrom L, Kaper JB, Lamikanra A.; 2002 Jan; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=120082

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Antigen 43 from Escherichia coli Induces Inter- and Intraspecies Cell Aggregation and Changes in Colony Morphology of Pseudomonas fluorescens. by Kjaergaard K, Schembri MA, Hasman H, Klemm P.; 2000 Sep 1; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=111355

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Antigen-43-Mediated Autoaggregation of Escherichia coli Is Blocked by Fimbriation. by Hasman H, Chakraborty T, Klemm P.; 1999 Aug 15; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=93969

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Antimicrobial Resistance of Escherichia coli O157 Isolated from Humans, Cattle, Swine, and Food. by Schroeder CM, Zhao C, DebRoy C, Torcolini J, Zhao S, White DG, Wagner DD, McDermott PF, Walker RD, Meng J.; 2002 Feb; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=126736

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Application of Multiplex PCR for Detection of Non-O157 Verocytotoxin-Producing Escherichia coli in Bloody Stools: Identification of Serogroups O26 and O111. by Louie M, Read S, Simor AE, Holland J, Louie L, Ziebell K, Brunton J, Hii J.; 1998 Nov; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=105335

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Arginine Catabolism and the Arginine Succinyltransferase Pathway in Escherichia coli. by Schneider BL, Kiupakis AK, Reitzer LJ.; 1998 Aug 15; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=107427

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Assembly of the K40 Antigen in Escherichia coli: Identification of a Novel Enzyme Responsible for Addition of l-Serine Residues to the Glycan Backbone and Its Requirement for K40 Polymerization. by Amor PA, Yethon JA, Monteiro MA, Whitfield C.; 1999 Feb 1; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=93442

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Association of Enterohemorrhagic Escherichia coli Hemolysin with Serotypes of Shiga-Like-Toxin-Producing Escherichia coli of Human and Bovine Origins. by Gyles C, Johnson R, Gao A, Ziebell K, Pierard D, Aleksic S, Boerlin P.; 1998 Nov; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=106619

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Association of Escherichia coli ribosomes with the inner membrane requires the signal recognition particle receptor but is independent of the signal recognition particle. by Herskovits AA, Bibi E.; 2000 Apr 25; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=18282

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atp Mutants of Escherichia coli Fail To Grow on Succinate Due to a Transport Deficiency. by Boogerd FC, Boe L, Michelsen O, Jensen PR.; 1998 Nov 15; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=107657

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Augmentation of Killing of Escherichia coli O157 by Combinations of Lactate, Ethanol, and Low-pH Conditions. by Jordan SL, Glover J, Malcolm L, Thomson-Carter FM, Booth IR, Park SF.; 1999 Mar; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=91179

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Availability of Glutamate and Arginine during Acid Challenge Determines Cell Density-Dependent Survival Phenotype of Escherichia coli Strains. by Cui S, Meng J, Bhagwat AA.; 2001 Oct; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=93249

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Bacteremia Due to Extended-Spectrum [beta]-Lactamase-Producing Escherichia coli and Klebsiella pneumoniae in a Pediatric Oncology Ward: Clinical Features and Identification of Different Plasmids Carrying both SHV-5 and TEM-1 Genes. by Siu LK, Lu PL, Hsueh PR, Lin FM, Chang SC, Luh KT, Ho M, Lee CY.; 1999 Dec; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=85870

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Bacterial Hemoglobins and Flavohemoglobins for Alleviation of Nitrosative Stress in Escherichia coli. by Frey AD, Farres J, Bollinger CJ, Kallio PT.; 2002 Oct; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=126413

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Bicarbonate Ion Stimulates the Expression of Locus of Enterocyte EffacementEncoded Genes in Enterohemorrhagic Escherichia coli O157:H7. by Abe H, Tatsuno I, Tobe T, Okutani A, Sasakawa C.; 2002 Jul; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=128104

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Biocontrol of Escherichia coli O157 with O157-Specific Bacteriophages. by Kudva IT, Jelacic S, Tarr PI, Youderian P, Hovde CJ.; 1999 Sep; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=99698

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Biodegradation of Aromatic Compounds by Escherichia coli. by Diaz E, Ferrandez A, Prieto MA, Garcia JL.; 2001 Dec; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=99040

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Can Results Obtained with Commercially Available MicroScan Microdilution Panels Serve as an Indicator of [beta]-Lactamase Production among Escherichia coli and Klebsiella Isolates with Hidden Resistance to ExpandedSpectrum Cephalosporins and Aztreonam? by Moland ES, Sanders CC, Thomson KS.; 1998 Sep; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=105165

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Cattle Can Be a Reservoir of Sorbitol-Fermenting Shiga Toxin-Producing Escherichia coli O157:H[minus sign] Strains and a Source of Human Diseases. by Bielaszewska M, Schmidt H, Liesegang A, Prager R, Rabsch W, Tschape H, Cizek A, Janda J, Blahova K, Karch H.; 2000 Sep; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=87410

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Cattle Water Troughs as Reservoirs of Escherichia coli O157. by LeJeune JT, Besser TE, Hancock DD.; 2001 Jul; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=92980

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Ceftazidime-Resistant Klebsiella pneumoniae and Escherichia coli Isolates Producing TEM-10 and TEM-43 [beta]-Lactamases from St. Louis, Missouri. by Yang Y, Bhachech N, Bradford PA, Jett BD, Sahm DF, Bush K.; 1998 Jul; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=105664

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Cell Division in Escherichia coli: Role of FtsL Domains in Septal Localization, Function, and Oligomerization. by Ghigo JM, Beckwith J.; 2000 Jan 1; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=94247

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Changes in Ribosomal Activity of Escherichia coli Cells during Prolonged Culture in Sea Salts Medium. by Kalpaxis DL, Karahalios P, Papapetropoulou M.; 1998 Jun 15; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=107811

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Characterization of a region of the IncHI2 plasmid R478 which protects Escherichia coli from toxic effects specified by components of the tellurite, phage, and colicin resistance cluster. by Whelan KF, Sherburne RK, Taylor DE.; 1997 Jan; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&rendertype=abstr act&artid=178662

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Characterization of Atypical Enteropathogenic Escherichia coli Strains Harboring the astA Gene That Were Associated with a Waterborne Outbreak of Diarrhea in Japan. by Yatsuyanagi J, Saito S, Miyajima Y, Amano KI, Enomoto K.; 2003 May; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=154716

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Characterization of Chloramphenicol and Florfenicol Resistance in Escherichia coli Associated with Bovine Diarrhea. by White DG, Hudson C, Maurer JJ, Ayers S, Zhao S, Lee MD, Bolton L, Foley T, Sherwood J.; 2000 Dec; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=87642

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Characterization of Chloramphenicol Resistance in Beta-Hemolytic Escherichia coli Associated with Diarrhea in Neonatal Swine. by Bischoff KM, White DG, McDermott PF, Zhao S, Gaines S, Maurer JJ, Nisbet DJ.; 2002 Feb; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=153409

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Characterization of Enteropathogenic and Enteroaggregative Escherichia coli Isolated from Diarrheal Outbreaks. by Yatsuyanagi J, Saito S, Sato H, Miyajima Y, Amano KI, Enomoto K.; 2002 Jan; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=120118

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Characterization of Multidrug-Resistant Escherichia coli Isolates Associated with Nosocomial Infections in Dogs. by Sanchez S, McCrackin Stevenson MA, Hudson CR, Maier M, Buffington T, Dam Q, Maurer JJ.; 2002 Oct; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=130861

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Characterization of Mutations That Allow p-Aminobenzoyl-Glutamate Utilization by Escherichia coli. by Hussein MJ, Green JM, Nichols BP.; 1998 Dec 1; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=107711

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Characterization of Saa, a Novel Autoagglutinating Adhesin Produced by Locus of Enterocyte Effacement-Negative Shiga-Toxigenic Escherichia coli Strains That Are Virulent for Humans. by Paton AW, Srimanote P, Woodrow MC, Paton JC.; 2001 Nov; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=100080

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Characterization of SepL of Enterohemorrhagic Escherichia coli. by Kresse AU, Beltrametti F, Muller A, Ebel F, Guzman CA.; 2000 Nov 15; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=94797

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Characterization of Shiga Toxin-Producing Escherichia coli O157:H7 Isolated in Italy and in France. by Giammanco GM, Pignato S, Grimont F, Grimont PA, Caprioli A, Morabito S, Giammanco G.; 2002 Dec; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=154647

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Characterization of the Depletion of 2-C-Methyl-d-Erythritol-2,4-Cyclodiphosphate Synthase in Escherichia coli and Bacillus subtilis. by Campbell TL, Brown ED.; 2002 Oct; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=139617

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Characterization of the Distal Tail Fiber Locus and Determination of the Receptor for Phage AR1, Which Specifically Infects Escherichia coli O157:H7. by Yu SL, Ko KL, Chen CS, Chang YC, Syu WJ.; 2000 Nov 1; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=94728

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Characterization of the fomA and fomB Gene Products from Streptomyces wedmorensis, Which Confer Fosfomycin Resistance on Escherichia coli. by Kobayashi S, Kuzuyama T, Seto H.; 2000 Mar; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=89740

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Characterization of Unexpected Growth of Escherichia coli O157:H7 by Modeling. by Cornu M, Delignette-Muller ML, Flandrois JP.; 1999 Dec; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=91723

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Chimeric Vitreoscilla Hemoglobin (VHb) Carrying a Flavoreductase Domain Relieves Nitrosative Stress in Escherichia coli: New Insight into the Functional Role of VHb. by Kaur R, Pathania R, Sharma V, Mande SC, Dikshit KL.; 2002 Jan; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=126558

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Chloramphenicol causes fusion of separated nucleoids in Escherichia coli K-12 cells and filaments. by van Helvoort JM, Kool J, Woldringh CL.; 1996 Jul; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&rendertype=abstr act&artid=178188

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Chromosomal Regions Specific to Pathogenic Isolates of Escherichia coli Have a Phylogenetically Clustered Distribution. by Boyd EF, Hartl DL.; 1998 Mar 1; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=107003

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Chronic Prosthetic Hip Infection Caused by a Small-Colony Variant of Escherichia coli. by Roggenkamp A, Sing A, Hornef M, Brunner U, Autenrieth IB, Heesemann J.; 1998 Sep; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=105157

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Citrobacter rodentium, the Causative Agent of Transmissible Murine Colonic Hyperplasia, Exhibits Clonality: Synonymy of C. rodentium and Mouse-Pathogenic Escherichia coli. by Luperchio SA, Newman JV, Dangler CA, Schrenzel MD, Brenner DJ, Steigerwalt AG, Schauer DB.; 2000 Dec; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=87603

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Clindamycin Suppresses Endotoxin Released by Ceftazidime-Treated Escherichia coli O55:B5 and Subsequent Production of Tumor Necrosis Factor Alpha and Interleukin1[beta]. by Kishi K, Hirai K, Hiramatsu K, Yamasaki T, Nasu M.; 1999 Mar; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=89169

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Clinical Escherichia coli Strains Carrying stx Genes: stx Variants and stx-Positive Virulence Profiles. by Eklund M, Leino K, Siitonen A.; 2002 Dec; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=154619

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Clinical Isolates of Non-O157 Shiga Toxin-Producing Escherichia coli: Serotypes, Virulence Characteristics, and Molecular Profiles of Strains of the Same Serotype. by Eklund M, Scheutz F, Siitonen A.; 2001 Aug; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=88246

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Clonal Diversity of Chilean Isolates of Enterohemorrhagic Escherichia coli from Patients with Hemolytic-Uremic Syndrome, Asymptomatic Subjects, Animal Reservoirs, and Food Products. by Rios M, Prado V, Trucksis M, Arellano C, Borie C, Alexandre M, Fica A, Levine MM.; 1999 Mar; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=84553

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Cloning of the Lactococcus lactis adhE Gene, Encoding a Multifunctional Alcohol Dehydrogenase, by Complementation of a Fermentative Mutant of Escherichia coli. by Arnau J, Jorgensen F, Madsen SM, Vrang A, Israelsen H.; 1998 Jun 15; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=107803

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Colocalization of cell division proteins FtsZ and FtsA to cytoskeletal structures in living Escherichia coli cells by using green fluorescent protein. by Ma X, Ehrhardt DW, Margolin W.; 1996 Nov 12; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=24035

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Combined Use of Two Genetic Fingerprinting Methods, Pulsed-Field Gel Electrophoresis and Ribotyping, for Characterization of Escherichia coli O157 Isolates from Food Animals, Retail Meats, and Cases of Human Disease. by Avery SM, Liebana E, Reid CA, Woodward MJ, Buncic S.; 2002 Aug; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=120670

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Combined, Functional Genomic-Biochemical Approach to Intermediary Metabolism: Interaction of Acivicin, a Glutamine Amidotransferase Inhibitor, with Escherichia coli K-12. by Smulski DR, Huang LL, McCluskey MP, Reeve MJ, Vollmer AC, Van Dyk TK, LaRossa RA.; 2001 Jun 1; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=99633

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Comparative Survival of Free Shiga Toxin 2-Encoding Phages and Escherichia coli Strains outside the Gut. by Muniesa M, Lucena F, Jofre J.; 1999 Dec; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=91769

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Comparison of [Delta]relA Strains of Escherichia coli and Salmonella enterica Serovar Typhimurium Suggests a Role for ppGpp in Attenuation Regulation of Branched-Chain Amino Acid Biosynthesis. by Tedin K, Norel F.; 2001 Nov 1; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=100096

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Comparison of Escherichia coli O157:H7 Antigen Detection in Stool and Broth Cultures to That in Sorbitol-MacConkey Agar Stool Cultures. by Stapp JR, Jelacic S, Yea YL, Klein EJ, Fischer M, Clausen CR, Qin X, Swerdlow DL, Tarr PI.; 2000 Sep; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=87394

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Comparison of the BAX for Screening/E. coli O157:H7 Method with Conventional Methods for Detection of Extremely Low Levels of Escherichia coli O157:H7 in Ground Beef. by Johnson JL, Brooke CL, Fritschel SJ.; 1998 Nov; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=106658

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Competition among seven Escherichia coli [sigma] subunits: relative binding affinities to the core RNA polymerase. by Maeda H, Fujita N, Ishihama A.; 2000 Sep 15; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=110723

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Comprehensive Studies of Drug Resistance Mediated by Overexpression of Response Regulators of Two-Component Signal Transduction Systems in Escherichia coli. by Hirakawa H, Nishino K, Hirata T, Yamaguchi A.; 2003 Mar; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=150137

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Concentration and Prevalence of Escherichia coli O157 in Cattle Feces at Slaughter. by Omisakin F, MacRae M, Ogden ID, Strachan NJ.; 2003 May; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=154535

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Concomitant Infection of Enterotoxigenic Escherichia coli in an Outbreak of Cholera Caused by Vibrio cholerae O1 and O139 in Ahmedabad, India. by Chakraborty S, Deokule JS, Garg P, Bhattacharya SK, Nandy RK, Nair GB, Yamasaki S, Takeda Y, Ramamurthy T.; 2001 Sep; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=88325

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Conjugative Junctions in RP4-Mediated Mating of Escherichia coli. by Samuels AL, Lanka E, Davies JE.; 2000 May 15; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=101974

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Constitutive Septal Murein Synthesis in Escherichia coli with Impaired Activity of the Morphogenetic Proteins RodA and Penicillin-Binding Protein 2. by de Pedro MA, Donachie WD, Holtje JV, Schwarz H.; 2001 Jul 15; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=95299

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Construction and Characterization of Genetically Defined aro omp Mutants of Enterotoxigenic Escherichia coli and Preliminary Studies of Safety and Immunogenicity in Humans. by Turner AK, Terry TD, Sack DA, Londono-Arcila P, Darsley MJ.; 2001 Aug; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=98589

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Construction of Environmental DNA Libraries in Escherichia coli and Screening for the Presence of Genes Conferring Utilization of 4-Hydroxybutyrate. by Henne A, Daniel R, Schmitz RA, Gottschalk G.; 1999 Sep; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=99718

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Contribution of dps to Acid Stress Tolerance and Oxidative Stress Tolerance in Escherichia coli O157:H7. by Choi SH, Baumler DJ, Kaspar CW.; 2000 Sep; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=92238

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Contribution of Escherichia coli Alpha-Hemolysin to Bacterial Virulence and to Intraperitoneal Alterations in Peritonitis. by May AK, Gleason TG, Sawyer RG, Pruett TL.; 2000 Jan; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=97118

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Contributions of PBP 5 and dd-Carboxypeptidase Penicillin Binding Proteins to Maintenance of Cell Shape in Escherichia coli. by Nelson DE, Young KD.; 2001 May 15; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=95205

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Control of Acid Resistance in Escherichia coli. by Castanie-Cornet MP, Penfound TA, Smith D, Elliott JF, Foster JW.; 1999 Jun 1; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=93821

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Convergent Pathways for Utilization of the Amino Sugars N-Acetylglucosamine, NAcetylmannosamine, and N-Acetylneuraminic Acid by Escherichia coli. by Plumbridge J, Vimr E.; 1999 Jan 1; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=103530

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Cytoplasmic RNA Polymerase in Escherichia coli. by Shepherd N, Dennis P, Bremer H.; 2001 Apr 15; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=95169

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Decreased Adherence of Enterohemorrhagic Escherichia coli to HEp-2 Cells in the Presence of Antibodies That Recognize the C-Terminal Region of Intimin. by Gansheroff LJ, Wachtel MR, O'Brien AD.; 1999 Dec; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=97049

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Detection and Characterization of Shiga Toxigenic Escherichia coli by Using Multiplex PCR Assays for stx1, stx2, eaeA, Enterohemorrhagic E. coli hlyA, rfbO111, and rfbO157. by Paton AW, Paton JC.; 1998 Feb; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=104589

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Detection in Escherichia coli of the Genes Encoding the Major Virulence Factors, the Genes Defining the O157:H7 Serotype, and Components of the Type 2 Shiga Toxin Family by Multiplex PCR. by Wang G, Clark CG, Rodgers FG.; 2002 Oct; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=130888

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Detection of Florfenicol Resistance Genes in Escherichia coli Isolated from Sick Chickens. by Keyes K, Hudson C, Maurer JJ, Thayer S, White DG, Lee MD.; 2000 Feb; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=89696

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Detection of Hemolysin Variants of Shiga Toxin-Producing Escherichia coli by PCR and Culture on VancomycinCefixime-Cefsulodin Blood Agar. by Lehmacher A, Meier H, Aleksic S, Bockemuhl J.; 1998 Jul; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=106410

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Detection of mRNA by Reverse Transcription-PCR as an Indicator of Viability in Escherichia coli Cells. by Sheridan GE, Masters CI, Shallcross JA, Mackey BM.; 1998 Apr; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=106147

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Determinants of activation by complement of group II phospholipase A2 acting against Escherichia coli. by Madsen LM, Inada M, Weiss J.; 1996 Jul; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&rendertype=abstr act&artid=174093

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Determination of Pyrimidine Dimers in Escherichia coli and Cryptosporidium parvum during UV Light Inactivation, Photoreactivation, and Dark Repair. by Oguma K, Katayama H, Mitani H, Morita S, Hirata T, Ohgaki S.; 2001 Oct; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=93213

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Development and Characterization of a Fluorescent-Bacteriophage Assay for Detection of Escherichia coli O157:H7. by Goodridge L, Chen J, Griffiths M.; 1999 Apr; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=91198

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Development of a Colony Lift Immunoassay To Facilitate Rapid Detection and Quantification of Escherichia coli O157:H7 from Agar Plates and Filter Monitor Membranes. by Ingram DT, Lamichhane CM, Rollins DM, Carr LE, Mallinson ET, Joseph SW.; 1998 Jul; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=95619

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Development of Primers to O-Antigen Biosynthesis Genes for Specific Detection of Escherichia coli O157 by PCR. by Maurer JJ, Schmidt D, Petrosko P, Sanchez S, Bolton L, Lee MD.; 1999 Jul; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=91442

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Diarrheagenic Escherichia coli and Acute and Persistent Diarrhea in Returned Travelers. by Schultsz C, van den Ende J, Cobelens F, Vervoort T, van Gompel A, Wetsteyn JC, Dankert J.; 2000 Oct; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=87435

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Differential Expression of over 60 Chromosomal Genes in Escherichia coli by Constitutive Expression of MarA. by Barbosa TM, Levy SB.; 2000 Jun 15; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=101932

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Differential Regulation of Multiple Proteins of Escherichia coli and Salmonella enterica Serovar Typhimurium by the Transcriptional Regulator SlyA. by Spory A, Bosserhoff A, von Rhein C, Goebel W, Ludwig A.; 2002 Jul; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=135123

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Differential Responses of Escherichia coli Cells Expressing Cytoplasmic Domain Mutants of Penicillin-Binding Protein 1b after Impairment of Penicillin-Binding Proteins 1a and 3. by Chalut C, Charpentier X, Remy MH, Masson JM.; 2001 Jan 1; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=94866

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Diffusely Adherent Escherichia coli as a Cause of Acute Diarrhea in Young Children in Northeast Brazil: a Case-Control Study. by Scaletsky IC, Fabbricotti SH, Carvalho RL, Nunes CR, Maranhao HS, Morais MB, Fagundes-Neto U.; 2002 Feb; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=153384

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Direct Detection of Shiga Toxigenic Escherichia coli Strains Belonging to Serogroups O111, O157, and O113 by Multiplex PCR. by Paton AW, Paton JC.; 1999 Oct; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=85568

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Discriminatory Detection of Inhibitor-Resistant [beta]-Lactamases in Escherichia coli by Single-Strand Conformation Polymorphism-PCR. by Speldooren V, Heym B, Labia R, Nicolas-Chanoine MH.; 1998 Apr; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=105559

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Display of Passenger Proteins on the Surface of Escherichia coli K-12 by the Enterohemorrhagic E. coli Intimin EaeA. by Wentzel A, Christmann A, Adams T, Kolmar H.; 2001 Dec 15; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=95577

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Dissecting the functional program of Escherichia coli promoters: the combined mode of action of Lac repressor and AraC activator. by Lutz R, Lozinski T, Ellinger T, Bujard H.; 2001 Sep 15; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=55909

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Distribution of Core Oligosaccharide Types in Lipopolysaccharides from Escherichia coli. by Amor K, Heinrichs DE, Frirdich E, Ziebell K, Johnson RP, Whitfield C.; 2000 Mar; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=97256

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Diversification of Escherichia coli Expressing an SHV-Type Extended-Spectrum [beta]-Lactamase (ESBL) during a Hospital Outbreak: Emergence of an ESBLHyperproducing Strain Resistant to Expanded-Spectrum Cephalosporins. by Palucha A, Mikiewicz B, Gniadkowski M.; 1999 Feb; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=89087

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Diversity, Frequency, and Persistence of Escherichia coli O157 Strains from Range Cattle Environments. by Renter DG, Sargeant JM, Oberst RD, Samadpour M.; 2003 Jan; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=152399

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DNA damage-dependent recruitment of nucleotide excision repair and transcription proteins to Escherichia coli inner membranes. by Lin CG, Kovalsky O, Grossman L.; 1997 Aug 1; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&rendertype=abstr act&artid=146856

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DNA Microarray Analyses of the Long-Term Adaptive Response of Escherichia coli to Acetate and Propionate. by Polen T, Rittmann D, Wendisch VF, Sahm H.; 2003 Mar; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=150104

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DNA Microarray-Based Identification of Genes Controlled by Autoinducer 2Stimulated Quorum Sensing in Escherichia coli. by DeLisa MP, Wu CF, Wang L, Valdes JJ, Bentley WE.; 2001 Sep 15; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=95404

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DnaA, the Initiator of Escherichia coli Chromosomal Replication, Is Located at the Cell Membrane. by Newman G, Crooke E.; 2000 May 1; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=111327

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Down regulation of intimin expression during attaching and effacing enteropathogenic Escherichia coli adhesion. by Knutton S, Adu-Bobie J, Bain C, Phillips AD, Dougan G, Frankel G.; 1997 May; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&rendertype=abstr act&artid=175190

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Dr Operon-Associated Invasiveness of Escherichia coli from Pregnant Patients with Pyelonephritis. by Goluszko P, Niesel D, Nowicki B, Selvarangan R, Nowicki S, Hart A, Pawelczyk E, Das M, Urvil P, Hasan R.; 2001 Jul; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=98548

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Efa1 Influences Colonization of the Bovine Intestine by Shiga Toxin-Producing Escherichia coli Serotypes O5 and O111. by Stevens MP, van Diemen PM, Frankel G, Phillips AD, Wallis TS.; 2002 Sep; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=128238

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Effects of Growth Mode and Pyruvate Carboxylase on Succinic Acid Production by Metabolically Engineered Strains of Escherichia coli. by Vemuri GN, Eiteman MA, Altman E.; 2002 Apr; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=123851

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Effects of Multiple Deletions of Murein Hydrolases on Viability, Septum Cleavage, and Sensitivity to Large Toxic Molecules in Escherichia coli. by Heidrich C, Ursinus A, Berger J, Schwarz H, Holtje JV.; 2002 Nov; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=151956

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Electrophoretic Mobilities of Escherichia coli O157:H7 and Wild-Type Escherichia coli Strains. by Lytle DA, Rice EW, Johnson CH, Fox KR.; 1999 Jul; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=91477

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Emergence of Fosfomycin-Resistant Isolates of Shiga-Like Toxin-Producing Escherichia coli O26. by Horii T, Kimura T, Sato K, Shibayama K, Ohta M.; 1999 Apr; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=89208

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Endogenous Superoxide Dismutase Levels Regulate Iron-Dependent Hydroxyl Radical Formation in Escherichia coli Exposed to Hydrogen Peroxide. by McCormick ML, Buettner GR, Britigan BE.; 1998 Feb 1; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=106930

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Endonuclease V (nfi) Mutant of Escherichia coli K-12. by Guo G, Weiss B.; 1998 Jan 1; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=106847

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Engineering a Homo-Ethanol Pathway in Escherichia coli: Increased Glycolytic Flux and Levels of Expression of Glycolytic Genes during Xylose Fermentation. by Tao H, Gonzalez R, Martinez A, Rodriguez M, Ingram LO, Preston JF, Shanmugam KT.; 2001 May 15; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=95196

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Enhanced Production of Recombinant Proteins in Escherichia coli by Filamentation Suppression. by Jeong KJ, Lee SY.; 2003 Feb; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=143674

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Enhancement of Expression and Apparent Secretion of Erwinia chrysanthemi Endoglucanase (Encoded by celZ) in Escherichia coli B. by Zhou S, Yomano LP, Saleh AZ, Davis FC, Aldrich HC, Ingram LO.; 1999 Jun; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=91359

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Enterohemorrhagic Escherichia coli (EHEC) Strains of Serogroup O118 Display Three Distinctive Clonal Groups of EHEC Pathogens. by Wieler LH, Busse B, Steinruck H, Beutin L, Weber A, Karch H, Baljer G.; 2000 Jun; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=86754

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Entry into and Release of Solvents by Escherichia coli in an Organic-Aqueous TwoLiquid-Phase System and Substrate Specificity of the AcrAB-TolC Solvent-Extruding Pump. by Tsukagoshi N, Aono R.; 2000 Sep 1; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=111357

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Epidemiological Study of pap Genes among Diarrheagenic or Septicemic Escherichia coli Strains Producing CS31A and F17 Adhesins and Characterization of Pap31A Fimbriae. by Bertin Y, Girardeau JP, Darfeuille-Michaud A, Martin C.; 2000 Apr; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=86476

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Escherichia coli DNA Polymerase IV Mutator Activity: Genetic Requirements and Mutational Specificity. by Wagner J, Nohmi T.; 2000 Aug 15; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=94631

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Escherichia coli Gene Expression Responsive to Levels of the Response Regulator EvgA. by Masuda N, Church GM.; 2002 Nov; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=151933

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Escherichia coli genes regulated by cell-to-cell signaling. by Baca-DeLancey RR, South MM, Ding X, Rather PN.; 1999 Apr 13; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=16380

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Escherichia coli Hemoglobin Protease Autotransporter Contributes to Synergistic Abscess Formation and Heme-Dependent Growth of Bacteroides fragilis. by Otto BR, van Dooren SJ, Dozois CM, Luirink J, Oudega B.; 2002 Jan; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=127594

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Escherichia coli in settled-dust and air samples collected in residential environments in Mexico City. by Rosas I, Salinas E, Yela A, Calva E, Eslava C, Cravioto A.; 1997 Oct; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&rendertype=abstr act&artid=168722

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Escherichia coli msbB Gene as a Virulence Factor and a Therapeutic Target. by Somerville JE Jr, Cassiano L, Darveau RP.; 1999 Dec; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=97070

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Escherichia coli O157:H7 and O157:H[minus sign] Strains That Do Not Produce Shiga Toxin: Phenotypic and Genetic Characterization of Isolates Associated with Diarrhea and Hemolytic-Uremic Syndrome. by Schmidt H, Scheef J, Huppertz HI, Frosch M, Karch H.; 1999 Nov; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=85676

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Escherichia coli Open Reading Frame 696 Is idi, a Nonessential Gene Encoding Isopentenyl Diphosphate Isomerase. by Hahn FM, Hurlburt AP, Poulter CD.; 1999 Aug 1; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=103578

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Escherichia coli Resistance to Chlorine and Glutathione Synthesis in Response to Oxygenation and Starvation. by Saby S, Leroy P, Block JC.; 1999 Dec; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=91765

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Escherichia coli Ribosome-Associated Protein SRA, Whose Copy Number Increases during Stationary Phase. by Izutsu K, Wada C, Komine Y, Sako T, Ueguchi C, Nakura S, Wada A.; 2001 May 1; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=99491

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Escherichia coli RNA Polymerase Is the Target of the Cyclopeptide Antibiotic Microcin J25. by Delgado MA, Rintoul MR, Farias RN, Salomon RA.; 2001 Aug 1; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=95349

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Escherichia coli RNA polymerase terminates transcription efficiently at rhoindependent terminators on single-stranded DNA templates. by Uptain SM, Chamberlin MJ.; 1997 Dec 9; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=28343

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Escherichia coli Strains Blocked in Tat-Dependent Protein Export Exhibit Pleiotropic Defects in the Cell Envelope. by Stanley NR, Findlay K, Berks BC, Palmer T.; 2001 Jan 1; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=94859

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Escherichia coli Strains from Pregnant Women and Neonates: Intraspecies Genetic Distribution and Prevalence of Virulence Factors. by Watt S, Lanotte P, Mereghetti L, Moulin-Schouleur M, Picard B, Quentin R.; 2003 May; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=154741

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Evaluation of a Microplate Latex Agglutination Method (Verotox-F Assay) for Detecting and Characterizing Verotoxins (Shiga Toxins) in Escherichia coli. by Karmali MA, Petric M, Bielaszewska M.; 1999 Feb; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=84318

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Evaluation of the premier EHEC assay for detection of Shiga toxin-producing Escherichia coli. by Kehl KS, Havens P, Behnke CE, Acheson DW.; 1997 Aug; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&rendertype=abstr act&artid=229901

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Evolution of Enterohemorrhagic Escherichia coli Hemolysin Plasmids and the Locus for Enterocyte Effacement in Shiga Toxin-Producing E. coli. by Boerlin P, Chen S, Colbourne JK, Johnson R, De Grandis S, Gyles C.; 1998 Jun; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=108238

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Evolutionary genetics of the isocitrate dehydrogenase gene (icd) in Escherichia coli and Salmonella enterica. by Wang FS, Whittam TS, Selander RK.; 1997 Nov; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&rendertype=abstr act&artid=179578

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Examination of Recovery In Vitro and In Vivo of Nonculturable Escherichia coli O157:H7. by Kolling GL, Matthews KR.; 2001 Sep; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=93111

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Exopolysaccharide Production Is Required for Development of Escherichia coli K-12 Biofilm Architecture. by Danese PN, Pratt LA, Kolter R.; 2000 Jun 15; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=101973

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Experimental and Field Studies of Escherichia coli O157:H7 in White-Tailed Deer. by Fischer JR, Zhao T, Doyle MP, Goldberg MR, Brown CA, Sewell CT, Kavanaugh DM, Bauman CD.; 2001 Mar; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=92716

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Experimental Escherichia coli O157:H7 carriage in calves. by Brown CA, Harmon BG, Zhao T, Doyle MP.; 1997 Jan; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&rendertype=abstr act&artid=168298

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Export of Virulence Genes and Shiga Toxin by Membrane Vesicles of Escherichia coli O157:H7. by Kolling GL, Matthews KR.; 1999 May; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=91264

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Expression and Characterization of Flagella in Nonmotile Enteroinvasive Escherichia coli Isolated from Diarrhea Cases. by Andrade A, Giron JA, Amhaz JM, Trabulsi LR, Martinez MB.; 2002 Oct; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=128341

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Expression in Escherichia coli of Native and Chimeric Phenolic Acid Decarboxylases with Modified Enzymatic Activities and Method for Screening Recombinant E. coli Strains Expressing These Enzymes. by Barthelmebs L, Divies C, Cavin JF.; 2001 Mar; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=92695

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Expression of Alcaligenes eutrophus Flavohemoprotein and Engineered Vitreoscilla Hemoglobin-Reductase Fusion Protein for Improved Hypoxic Growth of Escherichia coli. by Frey AD, Bailey JE, Kallio PT.; 2000 Jan; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=91791

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Expression of an Anaplerotic Enzyme, Pyruvate Carboxylase, Improves Recombinant Protein Production in Escherichia coli. by March JC, Eiteman MA, Altman E.; 2002 Nov; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=129945

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Extended Virulence Genotype of Pathogenic Escherichia coli Isolates Carrying the afa-8 Operon: Evidence of Similarities between Isolates from Humans and Animals with Extraintestinal Infections. by Girardeau JP, Lalioui L, Said AM, De Champs C, Le Bouguenec C.; 2003 Jan; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=149575

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Fate of Escherichia coli O157:H7 on Fresh-Cut Apple Tissue and Its Potential for Transmission by Fruit Flies. by Janisiewicz WJ, Conway WS, Brown MW, Sapers GM, Fratamico P, Buchanan RL.; 1999 Jan; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=90974

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Fate of pGFP-Bearing Escherichia coli O157:H7 in Ground Beef at 2 and 10[deg]C and Effects of Lactate, Diacetate, and Citrate. by Ajjarapu S, Shelef LA.; 1999 Dec; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=91734

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Ferritin Mutants of Escherichia coli Are Iron Deficient and Growth Impaired, and fur Mutants are Iron Deficient. by Abdul-Tehrani H, Hudson AJ, Chang YS, Timms AR, Hawkins C, Williams JM, Harrison PM, Guest JR, Andrews SC.; 1999 Mar 1; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=93529

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First isolation of the enterohaemorrhagic Escherichia coli O145:H- from cattle in feedlot in Argentina. by Padola NL, Sanz ME, Lucchesi PM, Blanco JE, Blanco J, Blanco M, Etcheverria AI, Arroyo GH, Parma AE.; 2002; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=102760

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FK506 Binding Protein from the Hyperthermophilic Archaeon Pyrococcus horikoshii Suppresses the Aggregation of Proteins in Escherichia coli. by Ideno A, Furutani M, Iba Y, Kurosawa Y, Maruyama T.; 2002 Feb; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=126703

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Flavodoxin Mutants of Escherichia coli K-12. by Gaudu P, Weiss B.; 2000 Apr 1; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=101859

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Flux through Citrate Synthase Limits the Growth of Ethanologenic Escherichia coli KO11 during Xylose Fermentation. by Underwood SA, Buszko ML, Shanmugam KT, Ingram LO.; 2002 Mar; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=123777

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Full Capacity of Recombinant Escherichia coli Heat-Stable Enterotoxin Fusion Proteins for Extracellular Secretion, Antigenicity, Disulfide Bond Formation, and Activity. by Batisson I, Der Vartanian M, Gaillard-Martinie B, Contrepois M.; 2000 Jul; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=101696

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Functional Analysis of the Signal Recognition Particle in Escherichia coli by Characterization of a Temperature-Sensitive ffh Mutant. by Park SK, Jiang F, Dalbey RE, Phillips GJ.; 2002 May; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=135024

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Functions of the Membrane-Associated and Cytoplasmic Malate Dehydrogenases in the Citric Acid Cycle of Escherichia coli. by van der Rest ME, Frank C, Molenaar D.; 2000 Dec 15; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=94812

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GcpE Is Involved in the 2-C-Methyl-d-Erythritol 4-Phosphate Pathway of Isoprenoid Biosynthesis in Escherichia coli. by Altincicek B, Kollas AK, Sanderbrand S, Wiesner J, Hintz M, Beck E, Jomaa H.; 2001 Apr 15; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=95155

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Gene Cluster for Assembly of Pilus Colonization Factor Antigen III of Enterotoxigenic Escherichia coli. by Taniguchi T, Akeda Y, Haba A, Yasuda Y, Yamamoto K, Honda T, Tochikubo K.; 2001 Sep; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=98705

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Gene Expression Profiling of the pH Response in Escherichia coli. by Tucker DL, Tucker N, Conway T.; 2002 Dec; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=135413

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Genes Involved in Copper Homeostasis in Escherichia coli. by Grass G, Rensing C.; 2001 Mar 15; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=95116

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Genes of the GadX-GadW Regulon in Escherichia coli. by Tucker DL, Tucker N, Ma Z, Foster JW, Miranda RL, Cohen PS, Conway T.; 2003 May; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=154079

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Genetic Analysis for Virulence Factors in Escherichia coli O104:H21 That Was Implicated in an Outbreak of Hemorrhagic Colitis. by Feng P, Weagant SD, Monday SR.; 2001 Jan; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=87673

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Genetic Analysis of the nuo Locus, Which Encodes the Proton-Translocating NADH Dehydrogenase in Escherichia coli. by Falk-Krzesinski HJ, Wolfe AJ.; 1998 Mar 1; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=107005

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Genetic Changes To Optimize Carbon Partitioning between Ethanol and Biosynthesis in Ethanologenic Escherichia coli. by Underwood SA, Zhou S, Causey TB, Yomano LP, Shanmugam KT, Ingram LO.; 2002 Dec; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=134451

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Genetic Characterization of Escherichia coli Populations from Host Sources of Fecal Pollution by Using DNA Fingerprinting. by McLellan SL, Daniels AD, Salmore AK.; 2003 May; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=154501

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Genetic Diversity of Intimin Genes of Attaching and Effacing Escherichia coli Strains. by Zhang WL, Kohler B, Oswald E, Beutin L, Karch H, Morabito S, Caprioli A, Suerbaum S, Schmidt H.; 2002 Dec; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=154638

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Genetic Interactions between the Escherichia coli umuDC Gene Products and the [beta] Processivity Clamp of the Replicative DNA Polymerase. by Sutton MD, Farrow MF, Burton BM, Walker GC.; 2001 May 1; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=99508

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Genomic Comparisons and Shiga Toxin Production among Escherichia coli O157:H7 Isolates from a Day Care Center Outbreak and Sporadic Cases in Southeastern Wisconsin. by Gouveia S, Proctor ME, Lee MS, Luchansky JB, Kaspar CW.; 1998 Mar; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=104616

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Genomic Subtraction To Identify and Characterize Sequences of Shiga ToxinProducing Escherichia coli O91:H21. by Pradel N, Leroy-Setrin S, Joly B, Livrelli V.; 2002 May; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=127536

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Genotype Analysis of Escherichia coli Strains Isolated from Children and Chickens Living in Close Contact. by Kariuki S, Gilks C, Kimari J, Obanda A, Muyodi J, Waiyaki P, Hart CA.; 1999 Feb; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=91049

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Genotypic Analyses of Escherichia coli O157:H7 and O157 Nonmotile Isolates Recovered from Beef Cattle and Carcasses at Processing Plants in the Midwestern States of the United States. by Barkocy-Gallagher GA, Arthur TM, Siragusa GR, Keen JE, Elder RO, Laegreid WW, Koohmaraie M.; 2001 Sep; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=93095

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Genotypic Analysis of Escherichia coli Strains from Poultry Carcasses and Their Susceptibilities to Antimicrobial Agents. by Geornaras I, Hastings JW, von Holy A.; 2001 Apr; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=92816

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Geographical Variation in Ribotype Profiles of Escherichia coli Isolates from Humans, Swine, Poultry, Beef, and Dairy Cattle in Florida. by Scott TM, Parveen S, Portier KM, Rose JB, Tamplin ML, Farrah SR, Koo A, Lukasik J.; 2003 Feb; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=143588

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Global genome removal of thymine glycol in Escherichia coli requires endonuclease III but the persistence of processed repair intermediates rather than thymine glycol correlates with cellular sensitivity to high doses of hydrogen peroxide. by Alanazi M, Leadon SA, Mellon I.; 2002 Nov 1; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=135796

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Global Molecular Epidemiology of the O15:K52:H1 Extraintestinal Pathogenic Escherichia coli Clonal Group: Evidence of Distribution beyond Europe. by Johnson JR, Stell AL, O'Bryan TT, Kuskowski M, Nowicki B, Johnson C, Maslow JN, Kaul A, Kavle J, Prats G.; 2002 Jun; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=130829

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Glutamate Decarboxylase Genes as a Prescreening Marker for Detection of Pathogenic Escherichia coli Groups. by Grant MA, Weagant SD, Feng P.; 2001 Jul; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=92988

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Gonococcal MinD Affects Cell Division in Neisseria gonorrhoeae and Escherichia coli and Exhibits a Novel Self-Interaction. by Szeto J, Ramirez-Arcos S, Raymond C, Hicks LD, Kay CM, Dillon JA.; 2001 Nov 1; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=100108

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Green Fluorescent Protein as a Noninvasive Stress Probe in Resting Escherichia coli Cells. by Cha HJ, Srivastava R, Vakharia VN, Rao G, Bentley WE.; 1999 Feb; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=91040

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Growth Phase-Coupled Alterations in Cell Structure and Function of Escherichia coli. by Makinoshima H, Aizawa SI, Hayashi H, Miki T, Nishimura A, Ishihama A.; 2003 Feb; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=142870

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Heat-Induced Expression and Chemically Induced Expression of the Escherichia coli Stress Protein HtpG Are Affected by the Growth Environment. by Mason CA, Dunner J, Indra P, Colangelo T.; 1999 Aug; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=91516

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HEp-2 cell adherence patterns, serotyping, and DNA analysis of Escherichia coli isolates from eight patients with AIDS and chronic diarrhea. by Polotsky Y, Nataro JP, Kotler D, Barrett TJ, Orenstein JM.; 1997 Aug; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&rendertype=abstr act&artid=229883

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High Frequency of Mutator Strains among Human Uropathogenic Escherichia coli Isolates. by Denamur E, Bonacorsi S, Giraud A, Duriez P, Hilali F, Amorin C, Bingen E, Andremont A, Picard B, Taddei F, Matic I.; 2002 Jan; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=139564

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High-Level Formation of Active Pseudomonas cepacia Lipase after Heterologous Expression of the Encoding Gene and Its Modified Chaperone in Escherichia coli and Rapid In Vitro Refolding. by Quyen DT, Schmidt-Dannert C, Schmid RD.; 1999 Feb; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=91096

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High-Level Production of Human Leptin by Fed-Batch Cultivation of Recombinant Escherichia coli and Its Purification. by Jeong KJ, Lee SY.; 1999 Jul; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=91452

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Homology of Escherichia coli R773 arsA, arsB, and arsC Genes in Arsenic-Resistant Bacteria Isolated from Raw Sewage and Arsenic-Enriched Creek Waters. by Saltikov CW, Olson BH.; 2002 Jan; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=126541

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Hypersensitivity of Escherichia coli [Delta](uvrB-bio) Mutants to 6Hydroxylaminopurine and Other Base Analogs Is Due to a Defect in Molybdenum Cofactor Biosynthesis. by Kozmin SG, Pavlov YI, Dunn RL, Schaaper RM.; 2000 Jun 15; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=101891

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Identification and Biosynthesis of Cyclic Enterobacterial Common Antigen in Escherichia coli. by Erbel PJ, Barr K, Gao N, Gerwig GJ, Rick PD, Gardner KH.; 2003 Mar; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=150143

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Identification and Characterization of a New Lipoprotein, NlpI, in Escherichia coli K12. by Ohara M, Wu HC, Sankaran K, Rick PD.; 1999 Jul 15; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=93934

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Identification and Characterization of a New Variant of Shiga Toxin 1 in Escherichia coli ONT:H19 of Bovine Origin. by Burk C, Dietrich R, Acar G, Moravek M, Bulte M, Martlbauer E.; 2003 May; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=154714

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Identification and Characterization of a Novel Genomic Island Integrated at selC in Locus of Enterocyte Effacement-Negative, Shiga Toxin-Producing Escherichia coli. by Schmidt H, Zhang WL, Hemmrich U, Jelacic S, Brunder W, Tarr PI, Dobrindt U, Hacker J, Karch H.; 2001 Nov; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=100065

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Identification and Characterization of aarF, a Locus Required for Production of Ubiquinone in Providencia stuartii and Escherichia coli and for Expression of 2[prime prime or minute]-N-Acetyltransferase in P. stuartii. by Macinga DR, Cook GM, Poole RK, Rather PN.; 1998 Jan 1; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=106858

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Identification and Characterization of Integron-Mediated Antibiotic Resistance among Shiga Toxin-Producing Escherichia coli Isolates. by Zhao S, White DG, Ge B, Ayers S, Friedman S, English L, Wagner D, Gaines S, Meng J.; 2001 Apr; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=92769

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Identification and Characterization of lpfABCC[prime prime or minute]DE, a Fimbrial Operon of Enterohemorrhagic Escherichia coli O157:H7. by Torres AG, Giron JA, Perna NT, Burland V, Blattner FR, Avelino-Flores F, Kaper JB.; 2002 Oct; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=128367

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Identification and Expression of Cephamycinase blaCMY Genes in Escherichia coli and Salmonella Isolates from Food Animals and Ground Meat. by Zhao S, White DG, McDermott PF, Friedman S, English L, Ayers S, Meng J, Maurer JJ, Holland R, Walker RD.; 2001 Dec; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=90890

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Identification of a family of intimins common to Escherichia coli causing attachingeffacing lesions in rabbits, humans, and swine. by Agin TS, Wolf MK.; 1997 Jan; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&rendertype=abstr act&artid=174596

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Identification of a New Iron-Regulated Virulence Gene, ireA, in an Extraintestinal Pathogenic Isolate of Escherichia coli. by Russo TA, Carlino UB, Johnson JR.; 2001 Oct; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=98753

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Identification of a protein secretory pathway for the secretion of heat-labile enterotoxin by an enterotoxigenic strain of Escherichia coli. by Tauschek M, Gorrell RJ, Strugnell RA, Robins-Browne RM.; 2002 May 14; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=124529

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Identification of CTX-M-14 Extended-Spectrum [beta]-Lactamase in Clinical Isolates of Shigella sonnei, Escherichia coli, and Klebsiella pneumoniae in Korea. by Pai H, Choi EH, Lee HJ, Hong JY, Jacoby GA.; 2001 Oct; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=88424

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Identification of Enterotoxigenic Escherichia coli Harboring Longus Type IV Pilus Gene by DNA Amplification. by Gutierrez-Cazarez Z, Qadri F, Albert MJ, Giron JA.; 2000 May; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=86583

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Identification of Escherichia coli ubiB, a Gene Required for the First Monooxygenase Step in Ubiquinone Biosynthesis. by Poon WW, Davis DE, Ha HT, Jonassen T, Rather PN, Clarke CF.; 2000 Sep 15; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=94662

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Identification of Fecal Escherichia coli from Humans and Animals by Ribotyping. by Carson CA, Shear BL, Ellersieck MR, Asfaw A.; 2001 Apr; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=92761

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Identification of OmpT as the Protease That Hydrolyzes the Antimicrobial Peptide Protamine before It Enters Growing Cells of Escherichia coli. by Stumpe S, Schmid R, Stephens DL, Georgiou G, Bakker EP.; 1998 Aug 1; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=107389

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Identification of proteins of Escherichia coli and Saccharomyces cerevisiae that specifically bind to C /C mismatches in DNA. by Nakahara T, Zhang QM, Hashiguchi K, Yonei S.; 2000 Jul 1; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=102710

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Identification of the Structural Gene for the TDP-Fuc4NAc:Lipid II Fuc4NAc Transferase Involved in Synthesis of Enterobacterial Common Antigen in Escherichia coli K-12. by Rahman A, Barr K, Rick PD.; 2001 Nov 15; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=95479

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Identification of yacE (CoaE) as the Structural Gene for Dephosphocoenzyme A Kinase in Escherichia coli K-12. by Mishra PK, Park PK, Drueckhammer DG.; 2001 May 1; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=99492

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Identification, Characterization, and Distribution of a Shiga Toxin 1 Gene Variant (stx1c) in Escherichia coli Strains Isolated from Humans. by Zhang W, Bielaszewska M, Kuczius T, Karch H.; 2002 Apr; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=140390

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Iha: a Novel Escherichia coli O157:H7 Adherence-Conferring Molecule Encoded on a Recently Acquired Chromosomal Island of Conserved Structure. by Tarr PI, Bilge SS, Vary JC Jr, Jelacic S, Habeeb RL, Ward TR, Baylor MR, Besser TE.; 2000 Mar; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=97294

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Imbalanced Base Excision Repair Increases Spontaneous Mutation and Alkylation Sensitivity in Escherichia coli. by Posnick LM, Samson LD.; 1999 Nov 1; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=94142

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Immunological Characterization of Escherichia coli O157:H7 Intimin [gamma]1. by Son WG, Graham TA, Gannon VP.; 2002 Jan; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=119882

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Impact of gyrA and parC Mutations on Quinolone Resistance, Doubling Time, and Supercoiling Degree of Escherichia coli. by Bagel S, Hullen V, Wiedemann B, Heisig P.; 1999 Apr; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=89219

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Importance of RpoS and Dps in Survival of Exposure of Both Exponential- and Stationary-Phase Escherichia coli Cells to the Electrophile N-Ethylmaleimide. by Ferguson GP, Creighton RI, Nikolaev Y, Booth IR.; 1998 Mar 1; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=106988

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Improvement of Posttranslational Bottlenecks in the Production of Penicillin Amidase in Recombinant Escherichia coli Strains. by Ignatova Z, Mahsunah A, Georgieva M, Kasche V.; 2003 Feb; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&rendertype=exter nal&artid=143610

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In Vitro Activities of Cephalosporins and Quinolones against Escherichia coli Strains Isolated from Diarrheic Dairy Calves. by Orden JA, Ruiz-Santa-Quiteria JA, Garcia S, Cid D, de la Fuente R.; 1999 Mar; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=89152

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In vivo characterization of the type A and B vancomycin-resistant enterococci (VRE) VanRS two-component systems in Escherichia coli: A nonpathogenic model for studying the VRE signal transduction pathways. by Silva JC, Haldimann A, Prahalad MK, Walsh CT, Wanner BL.; 1998 Sep 29; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=21746

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In Vivo Increase in Resistance to Ciprofloxacin in Escherichia coli Associated with Deletion of the C-Terminal Part of MarR. by Linde HJ, Notka F, Metz M, Kochanowski B, Heisig P, Lehn N.; 2000 Jul; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=89976

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Increased Expression of Periplasmic Cu,Zn Superoxide Dismutase Enhances Survival of Escherichia coli Invasive Strains within Nonphagocytic Cells. by Battistoni A, Pacello F, Folcarelli S, Ajello M, Donnarumma G, Greco R, Grazia Ammendolia M, Touati D, Rotilio G, Valenti P.; 2000 Jan; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=97098

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Increased Type 1 Fimbrial Expression among Commensal Escherichia coli Isolates in the Murine Cecum following Catabolic Stress. by Hendrickson BA, Guo J, Laughlin R, Chen Y, Alverdy JC.; 1999 Feb; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=96382

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Influence of S-Adenosylmethionine Pool Size on Spontaneous Mutation, Dam Methylation, and Cell Growth of Escherichia coli. by Posnick LM, Samson LD.; 1999 Nov 1; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=94141

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Inhibition of Attaching and Effacing Lesion Formation following Enteropathogenic Escherichia coli and Shiga Toxin-Producing E. coli Infection. by Johnson-Henry K, Wallace JL, Basappa NS, Soni R, Wu GK, Sherman PM.; 2001 Nov; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=100109

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Interaction of Enteropathogenic or Enterohemorrhagic Escherichia coli with HeLa Cells Results in Translocation of Cortactin to the Bacterial Adherence Site. by Cantarelli VV, Takahashi A, Akeda Y, Nagayama K, Honda T.; 2000 Jan; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=97145

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Interleukin-8 Secretion of Cortical Tubular Epithelial Cells Is Directed to the Basolateral Environment and Is Not Enhanced by Apical Exposure to Escherichia coli. by Kruger S, Brandt E, Klinger M, Kruger S, Kreft B.; 2000 Jan; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=97138

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Introduction of a Carboxyl Group in the First Transmembrane Helix of Escherichia coli F1Fo ATPase Subunit c and Cytoplasmic pH Regulation. by Jones PC.; 2001 Mar 1; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=95036

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Invasion Activity of a Mycobacterium tuberculosis Peptide Presented by the Escherichia coli AIDA Autotransporter. by Casali N, Konieczny M, Schmidt MA, Riley LW.; 2002 Dec; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=133103

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Invasive Ability of an Escherichia coli Strain Isolated from the Ileal Mucosa of a Patient with Crohn's Disease. by Boudeau J, Glasser AL, Masseret E, Joly B, DarfeuilleMichaud A.; 1999 Sep; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=96770

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IS1414, an Escherichia coli Insertion Sequence with a Heat-Stable Enterotoxin Gene Embedded in a Transposase-Like Gene. by McVeigh A, Fasano A, Scott DA, Jelacic S, Moseley SL, Robertson DC, Savarino SJ.; 2000 Oct; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=101527

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Isolation and Characterization of Mini-Tn5Km2 Insertion Mutants of Enterohemorrhagic Escherichia coli O157:H7 Deficient in Adherence to Caco-2 Cells. by Tatsuno I, Kimura H, Okutani A, Kanamaru K, Abe H, Nagai S, Makino K, Shinagawa H, Yoshida M, Sato K, Nakamoto J, Tobe T, Sasakawa C.; 2000 Oct; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=101558

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Isolation and Characterization of Verocytotoxin-Producing Escherichia coli O157 Strains from Dutch Cattle and Sheep. by Heuvelink AE, van den Biggelaar FL, de Boer E, Herbes RG, Melchers WJ, Huis In 't Veld JH, Monnens LA.; 1998 Apr; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=104654

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Lack of S-Adenosylmethionine Results in a Cell Division Defect in Escherichia coli. by Newman EB, Budman LI, Chan EC, Greene RC, Lin RT, Woldringh CL, D'Ari R.; 1998 Jul 15; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=107330

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Lethality of a Heat- and Phosphate-Catalyzed Glucose By-Product to Escherichia coli O157:H7 and Partial Protection Conferred by the rpoS Regulon. by Byrd JJ, Cheville AM, Bose JL, Kaspar CW.; 1999 Jun; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=91354

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Longitudinal Study of Escherichia coli O157 in a Cattle Finishing Unit. by Lahti E, Ruoho O, Rantala L, Hanninen ML, Honkanen-Buzalski T.; 2003 Jan; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=152377

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Longitudinal Study of Escherichia coli O157:H7 Dissemination on Four Dairy Farms in Wisconsin. by Shere JA, Bartlett KJ, Kaspar CW.; 1998 Apr; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=106160

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Long-Term Survival of Shiga Toxin-Producing Escherichia coli O26, O111, and O157 in Bovine Feces. by Fukushima H, Hoshina K, Gomyoda M.; 1999 Nov; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=91700

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Loss of Regulatory Protein RfaH Attenuates Virulence of Uropathogenic Escherichia coli. by Nagy G, Dobrindt U, Schneider G, Khan AS, Hacker J, Emody L.; 2002 Aug; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=128157

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LuxArray, a High-Density, Genomewide Transcription Analysis of Escherichia coli Using Bioluminescent Reporter Strains. by Van Dyk TK, DeRose EJ, Gonye GE.; 2001 Oct 1; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=95439

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Mapping Stress-Induced Changes in Autoinducer AI-2 Production in ChemostatCultivated Escherichia coli K-12. by DeLisa MP, Valdes JJ, Bentley WE.; 2001 May 1; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=99510

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matB, a Common Fimbrillin Gene of Escherichia coli, Expressed in a Genetically Conserved, Virulent Clonal Group. by Pouttu R, Westerlund-Wikstrom B, Lang H, Alsti K, Virkola R, Saarela U, Siitonen A, Kalkkinen N, Korhonen TK.; 2001 Aug 15; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=99526

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Mechanism of Uptake of a Cationic Water-Soluble Pyridinium Zinc Phthalocyanine across the Outer Membrane of Escherichia coli. by Minnock A, Vernon DI, Schofield J, Griffiths J, Parish JH, Brown SB.; 2000 Mar; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=89720

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Mechanisms of Decreased Susceptibility to Cefpodoxime in Escherichia coli. by Oliver A, Weigel LM, Rasheed JK, McGowan Jr. JE, Raney P, Tenover FC.; 2002 Dec; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=132766

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Metabolic Analysis of Escherichia coli in the Presence and Absence of the Carboxylating Enzymes Phosphoenolpyruvate Carboxylase and Pyruvate Carboxylase. by Gokarn RR, Eiteman MA, Altman E.; 2000 May; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=101421

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Metabolic Context and Possible Physiological Themes of [final sigma]54-Dependent Genes in Escherichia coli. by Reitzer L, Schneider BL.; 2001 Sep; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=99035

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Molecular Analysis of Shiga Toxigenic Escherichia coli O111:H[minus sign] Proteins Which React with Sera from Patients with Hemolytic-Uremic Syndrome. by Voss E, Paton AW, Manning PA, Paton JC.; 1998 Apr; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=108076

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Molecular and Biochemical Characterization of VEB-1, a Novel Class A ExtendedSpectrum [beta]-Lactamase Encoded by an Escherichia coli Integron Gene. by Poirel L, Naas T, Guibert M, Chaibi EB, Labia R, Nordmann P.; 1999 Mar; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=89162

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Molecular Basis for the Temperature Sensitivity of Escherichia coli pth(Ts). by CruzVera LR, Toledo I, Hernandez-Sanchez J, Guarneros G.; 2000 Mar 15; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=94448

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Molecular Characteristics and Epidemiological Significance of Shiga ToxinProducing Escherichia coli O26 Strains. by Zhang WL, Bielaszewska M, Liesegang A, Tschape H, Schmidt H, Bitzan M, Karch H.; 2000 Jun; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=86746

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Molecular Characterization of a Serotype O121:H19 Clone, a Distinct Shiga ToxinProducing Clone of Pathogenic Escherichia coli. by Tarr CL, Large TM, Moeller CL, Lacher DW, Tarr PI, Acheson DW, Whittam TS.; 2002 Dec; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=133070

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Molecular Characterization of the [beta]-N-Acetylglucosaminidase of Escherichia coli and Its Role in Cell Wall Recycling. by Cheng Q, Li H, Merdek K, Park JT.; 2000 Sep 1; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=111361

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Molecular Evolution of a Pathogenicity Island from Enterohemorrhagic Escherichia coli O157:H7. by Perna NT, Mayhew GF, Posfai G, Elliott S, Donnenberg MS, Kaper JB, Blattner FR.; 1998 Aug; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=108423

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Molecular Evolution of the Intimin Gene in O111 Clones of Pathogenic Escherichia coli. by Tarr CL, Whittam TS.; 2002 Jan; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=139570

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Molecular microbiological investigation of an outbreak of hemolytic-uremic syndrome caused by dry fermented sausage contaminated with Shiga-like toxinproducing Escherichia coli. by Paton AW, Ratcliff RM, Doyle RM, Seymour-Murray J, Davos D, Lanser JA, Paton JC.; 1996 Jul; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&rendertype=abstr act&artid=229082

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Multidrug-Resistant Urinary Tract Isolates of Escherichia coli: Prevalence and Patient Demographics in the United States in 2000. by Sahm DF, Thornsberry C, Mayfield DC, Jones ME, Karlowsky JA.; 2001 May; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=90480

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Multilaboratory Validation of Rapid Spot Tests for Identification of Escherichia coli. by York MK, Baron EJ, Clarridge JE, Thomson RB, Weinstein MP.; 2000 Sep; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=87392

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Multiplex Fluorogenic Real-Time PCR for Detection and Quantification of Escherichia coli O157:H7 in Dairy Wastewater Wetlands. by Ibekwe AM, Watt PM, Grieve CM, Sharma VK, Lyons SR.; 2002 Oct; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=126415

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Mutations in DnaA protein suppress the growth arrest of acidic phospholipiddeficient Escherichia coli cells. by Zheng W, Li Z, Skarstad K, Crooke E.; 2001 Mar 1; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=145488

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Nanomolar Levels of Dimethylsulfoniopropionate, Dimethylsulfonioacetate, and Glycine Betaine Are Sufficient To Confer Osmoprotection to Escherichia coli. by Cosquer A, Pichereau V, Pocard JA, Minet J, Cormier M, Bernard T.; 1999 Aug; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=91496

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Non-O157:H7 Stx2-Producing Escherichia coli Strains Associated with Sporadic Cases of Hemolytic-Uremic Syndrome in Adults. by Bonnet R, Souweine B, Gauthier G, Rich C, Livrelli V, Sirot J, Joly B, Forestier C.; 1998 Jun; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=104920

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Non-Target Gene Mutations in the Development of Fluoroquinolone Resistance in Escherichia coli. by Kern WV, Oethinger M, Jellen-Ritter AS, Levy SB.; 2000 Apr; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=89776

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Novel Single-Tube Agar-Based Test System for Motility Enhancement and Immunocapture of Escherichia coli O157:H7 by H7 Flagellar Antigen-Specific Antibodies. by Murinda SE, Nguyen LT, Ivey SJ, Almeida RA, Oliver SP.; 2002 Dec; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=154605

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Occurrence and Detection of AmpC Beta-Lactamases among Escherichia coli, Klebsiella pneumoniae, and Proteus mirabilis Isolates at a Veterans Medical Center. by Coudron PE, Moland ES, Thomson KS.; 2000 May; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=86590

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Occurrence of leu+ revertants under starvation cultures in Escherichia coli is growthdependent. by Jin J, Gao P, Mao Y.; 2002; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=115868

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One Hundred Seventy-Fold Increase in Excretion of an FV Fragment-Tumor Necrosis Factor Alpha Fusion Protein (sFV/TNF-[alpha]) from Escherichia coli Caused by the

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Synergistic Effects of Glycine and Triton X-100. by Yang J, Moyana T, MacKenzie S, Xia Q, Xiang J.; 1998 Aug; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=106785 •

One of Two Copies of the Gene for the Activatable Shiga Toxin Type 2d in Escherichia coli O91:H21 Strain B2F1 Is Associated with an Inducible Bacteriophage. by Teel LD, Melton-Celsa AR, Schmitt CK, O'Brien AD.; 2002 Aug; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=128153

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Optimization of Reverse Transcriptase PCR To Detect Viable Shiga-Toxin-Producing Escherichia coli. by McIngvale SC, Elhanafi D, Drake MA.; 2002 Feb; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=126677

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Origin of Contamination and Genetic Diversity of Escherichia coli in Beef Cattle. by Aslam M, Nattress F, Greer G, Yost C, Gill C, McMullen L.; 2003 May; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=154492

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Osmoprotection of Escherichia coli by Peptone Is Mediated by the Uptake and Accumulation of Free Proline but Not of Proline-Containing Peptides. by Amezaga MR, Booth IR.; 1999 Dec; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=91716

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Osmoregulation of Dimer Resolution at the Plasmid pJHCMW1 mwr Locus by Escherichia coli XerCD Recombination. by Pham H, Dery KJ, Sherratt DJ, Tolmasky ME.; 2002 Mar; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=134880

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Overexpression of Protein Disulfide Isomerase DsbC Stabilizes Multiple-DisulfideBonded Recombinant Protein Produced and Transported to the Periplasm in Escherichia coli. by Kurokawa Y, Yanagi H, Yura T.; 2000 Sep; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=92245

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Overexpression of the marA or soxS Regulatory Gene in Clinical Topoisomerase Mutants of Escherichia coli. by Oethinger M, Podglajen I, Kern WV, Levy SB.; 1998 Aug; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=105868

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Overexpression of the waaZ Gene Leads to Modification of the Structure of the Inner Core Region of Escherichia coli Lipopolysaccharide, Truncation of the Outer Core, and Reduction of the Amount of O Polysaccharide on the Cell Surface. by Frirdich E, Lindner B, Holst O, Whitfield C.; 2003 Mar; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=148070

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Oxazolidinone Resistance Mutations in 23S rRNA of Escherichia coli Reveal the Central Region of Domain V as the Primary Site of Drug Action. by Xiong L, Kloss P, Douthwaite S, Andersen NM, Swaney S, Shinabarger DL, Mankin AS.; 2000 Oct 1; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=110973

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Oxygen-Insensitive Nitroreductases: Analysis of the Roles of nfsA and nfsB in Development of Resistance to 5-Nitrofuran Derivatives in Escherichia coli. by Whiteway J, Koziarz P, Veall J, Sandhu N, Kumar P, Hoecher B, Lambert IB.; 1998 Nov 1; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=107609

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Particular Biochemical Profiles for Enterohemorrhagic Escherichia coli O157:H7 Isolates on the ID 32E System. by Leclercq A, Lambert B, Pierard D, Mahillon J.; 2001 Mar; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=87895

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Pas, a Novel Protein Required for Protein Secretion and Attaching and Effacing Activities of Enterohemorrhagic Escherichia coli. by Kresse AU, Schulze K, Deibel C, Ebel F, Rohde M, Chakraborty T, Guzman CA.; 1998 Sep 1; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=107443

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Pathogenesis and Diagnosis of Shiga Toxin-Producing Escherichia coli Infections. by Paton JC, Paton AW.; 1998 Jul; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=88891

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PCR for Detection of cdt-III and the Relative Frequencies of Cytolethal Distending Toxin Variant-Producing Escherichia coli Isolates from Humans and Cattle. by Clark CG, Johnson ST, Easy RH, Campbell JL, Rodgers FG.; 2002 Jul; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=120586

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PCR for Specific Detection of H7 Flagellar Variant of fliC among Extraintestinal Pathogenic Escherichia coli. by Johnson JR, Stell AL.; 2001 Oct; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=88415

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PCR-Based DNA Amplification and Presumptive Detection of Escherichia coli O157:H7 with an Internal Fluorogenic Probe and the 5[prime prime or minute] Nuclease (TaqMan) Assay. by Oberst RD, Hays MP, Bohra LK, Phebus RK, Yamashiro CT, Paszko-Kolva C, Flood SJ, Sargeant JM, Gillespie JR.; 1998 Sep; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=106737

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Penicillin Binding Protein 5 Affects Cell Diameter, Contour, and Morphology of Escherichia coli. by Nelson DE, Young KD.; 2000 Mar 15; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=94470

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Persistent Colonization of Sheep by Escherichia coli O157:H7 and Other E. coli Pathotypes. by Cornick NA, Booher SL, Casey TA, Moon HW.; 2000 Nov; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=92401

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Phenotypic and Genotypic Characterization of Avian Escherichia coli O86:K61 Isolates Possessing a Gamma-Like Intimin. by La Ragione RM, McLaren IM, Foster G, Cooley WA, Woodward MJ.; 2002 Oct; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=126447

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Phylogenetic Analysis of Enteroaggregative and Diffusely Adherent Escherichia coli. by Czeczulin JR, Whittam TS, Henderson IR, Navarro-Garcia F, Nataro JP.; 1999 Jun; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=96572

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Polymorphisms within EspA Filaments of Enteropathogenic and Enterohemorrhagic Escherichia coli. by Neves BC, Shaw RK, Frankel G, Knutton S.; 2003 Apr; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=152064

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Postsegregational Killing Mediated by the P1 Phage "Addiction Module" phd-doc Requires the Escherichia coli Programmed Cell Death System mazEF. by Hazan R, Sat B, Reches M, Engelberg-Kulka H.; 2001 Mar 15; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=95101

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Preprotein Translocation by a Hybrid Translocase Composed of Escherichia coli and Bacillus subtilis Subunits. by Swaving J, van Wely KH, Driessen AJ.; 1999 Nov 15; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=94177

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Presence and Characterization of Extraintestinal Pathogenic Escherichia coli Virulence Genes in F165-Positive E. coli Strains Isolated from Diseased Calves and Pigs. by Dezfulian H, Batisson I, Fairbrother JM, Lau PC, Nassar A, Szatmari G, Harel J.; 2003 Apr; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=153855

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Prevalence and Characteristics of Shiga Toxin-Producing Escherichia coli from Healthy Cattle in Japan. by Kobayashi H, Shimada J, Nakazawa M, Morozumi T, Pohjanvirta T, Pelkonen S, Yamamoto K.; 2001 Jan; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=92607

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Prevalence and Characterization of Shiga Toxin-Producing Escherichia coli Isolated from Cattle, Food, and Children during a One-Year Prospective Study in France. by Pradel N, Livrelli V, De Champs C, Palcoux JB, Reynaud A, Scheutz F, Sirot J, Joly B, Forestier C.; 2000 Mar; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=86328

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Prevalence of Enterotoxigenic Escherichia coli Strains Harboring the Longus Pilus Gene in Brazil. by Nishimura LS, Giron JA, Nunes SL, Guth BE.; 2002 Jul; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=120555

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Prevalence of Iron Transport Gene on Pathogenicity-Associated Island of Uropathogenic Escherichia coli in E. coli O157:H7 Containing Shiga Toxin Gene. by Ye C, Xu J.; 2001 Jun; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=88130

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Prevalence of Virulence Genes and Clonality in Escherichia coli Strains That Cause Bacteremia in Cancer Patients. by Hilali F, Ruimy R, Saulnier P, Barnabe C, Lebouguenec C, Tibayrenc M, Andremont A.; 2000 Jul; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=101677

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Prevalence, Antibiotic Susceptibility, and Diversity of Escherichia coli O157:H7 Isolates from a Longitudinal Study of Beef Cattle Feedlots. by Galland JC, Hyatt DR, Crupper SS, Acheson DW.; 2001 Apr; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=92778

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Production and characterization of monoclonal antibodies specific for the lipopolysaccharide of Escherichia coli O157. by Westerman RB, He Y, Keen JE, Littledike ET, Kwang J.; 1997 Mar; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&rendertype=abstr act&artid=229650

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Production of Poly(3-Hydroxybutyrate) by Fed-Batch Culture of Recombinant Escherichia coli with a Highly Concentrated Whey Solution. by Ahn WS, Park SJ, Lee SY.; 2000 Aug; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=92194

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Proliferative Enterocolitis Associated with Dual Infection with Enteropathogenic Escherichia coli and Lawsonia intracellularis in Rabbits. by Schauer DB, McCathey SN, Daft BM, Jha SS, Tatterson LE, Taylor NS, Fox JG.; 1998 Jun; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=104903

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Properties of a Revertant of Escherichia coli Viable in the Presence of Spermidine Accumulation: Increase in l-Glycerol 3-Phosphate. by Raj VS, Tomitori H, Yoshida M, Apirakaramwong A, Kashiwagi K, Takio K, Ishihama A, Igarashi K.; 2001 Aug 1; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=95343

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Protection of Chickens against Escherichia coli Infections by DNA Containing CpG Motifs. by Gomis S, Babiuk L, Godson DL, Allan B, Thrush T, Townsend H, Willson P, Waters E, Hecker R, Potter A.; 2003 Feb; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=145352

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Protein ProQ Influences Osmotic Activation of Compatible Solute Transporter ProP in Escherichia coli K-12. by Kunte HJ, Crane RA, Culham DE, Richmond D, Wood JM.; 1999 Mar 1; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=93544

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Proteome Analysis of Metabolically Engineered Escherichia coli Producing Poly(3Hydroxybutyrate). by Han MJ, Yoon SS, Lee SY.; 2001 Jan 1; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=94879

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Purine Catabolism in Escherichia coli and Function of Xanthine Dehydrogenase in Purine Salvage. by Xi H, Schneider BL, Reitzer L.; 2000 Oct 1; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=110974

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Quorum sensing controls expression of the type III secretion gene transcription and protein secretion in enterohemorrhagic and enteropathogenic Escherichia coli. by Sperandio V, Mellies JL, Nguyen W, Shin S, Kaper JB.; 1999 Dec 21; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=24796

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Quorum sensing in Escherichia coli, Salmonella typhimurium, and Vibrio harveyi: A new family of genes responsible for autoinducer production. by Surette MG, Miller MB, Bassler BL.; 1999 Feb 16; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=15544

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Random amplification of polymorphic DNA reveals serotype-specific clonal clusters among enterotoxigenic Escherichia coli strains isolated from humans. by Pacheco AB, Guth BE, Soares KC, Nishimura L, de Almeida DF, Ferreira LC.; 1997 Jun; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&rendertype=abstr act&artid=229778

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Rapid and Simple Determination of the Escherichia coli Phylogenetic Group. by Clermont O, Bonacorsi S, Bingen E.; 2000 Oct; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=92342

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Rapid Detection, Identification, and Enumeration of Escherichia coli Cells in Municipal Water by Chemiluminescent In Situ Hybridization. by Stender H, Broomer AJ, Oliveira K, Perry-O'Keefe H, Hyldig-Nielsen JJ, Sage A, Coull J.; 2001 Jan; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=92533

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Rapid Identification of Escherichia coli Pathotypes by Virulence Gene Detection with DNA Microarrays. by Bekal S, Brousseau R, Masson L, Prefontaine G, Fairbrother J, Harel J.; 2003 May; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=154688

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Recombinational Repair Is Critical for Survival of Escherichia coli Exposed to Nitric Oxide. by Spek EJ, Wright TL, Stitt MS, Taghizadeh NR, Tannenbaum SR, Marinus MG, Engelward BP.; 2001 Jan 1; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=94858

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Recurrent Infections and Chronic Colonization by an Escherichia coli Clone in the Respiratory Tract of a Patient with Severe Cystic Bronchiectasis. by Wang JY, Hsueh PR, Wang JT, Lee LN, Yang PC, Luh KT.; 2000 Jul; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=87025

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Reduction of Carriage of Enterohemorrhagic Escherichia coli O157:H7 in Cattle by Inoculation with Probiotic Bacteria. by Zhao T, Doyle MP, Harmon BG, Brown CA, Mueller PO, Parks AH.; 1998 Mar; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=104601

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Regulated Expression of the Escherichia coli lepB Gene as a Tool for Cellular Testing of Antimicrobial Compounds That Inhibit Signal Peptidase I In Vitro. by Barbosa MD, Lin S, Markwalder JA, Mills JA, DeVito JA, Teleha CA, Garlapati V, Liu C, Thompson A, Trainor GL, Kurilla MG, Pompliano DL.; 2002 Nov; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=128713

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Regulated underexpression and overexpression of the FliN protein of Escherichia coli and evidence for an interaction between FliN and FliM in the flagellar motor. by Tang H, Billings S, Wang X, Sharp L, Blair DF.; 1995 Jun; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&rendertype=abstr act&artid=177054

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Regulated underexpression of the FliM protein of Escherichia coli and evidence for a location in the flagellar motor distinct from the MotA/MotB torque generators. by Tang H, Blair DF.; 1995 Jun; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&rendertype=abstr act&artid=177053

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Regulation of malate dehydrogenase (mdh) gene expression in Escherichia coli in response to oxygen, carbon, and heme availability. by Park SJ, Cotter PA, Gunsalus RP.; 1995 Nov; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&rendertype=abstr act&artid=177521

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Regulation of rRNA Transcription Is Remarkably Robust: FIS Compensates for Altered Nucleoside Triphosphate Sensing by Mutant RNA Polymerases at Escherichia coli rrn P1 Promoters. by Bartlett MS, Gaal T, Ross W, Gourse RL.; 2000 Apr 1; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=101898

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Relationship between Membrane Damage and Cell Death in Pressure-Treated Escherichia coli Cells: Differences between Exponential- and Stationary-Phase Cells and Variation among Strains. by Pagan R, Mackey B.; 2000 Jul; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=92080

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Relationship between the Tsh Autotransporter and Pathogenicity of Avian Escherichia coli and Localization and Analysis of the tsh Genetic Region. by Dozois CM, Dho-Moulin M, Bree A, Fairbrother JM, Desautels C, Curtiss R III.; 2000 Jul; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=101714

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Release of Compact Nucleoids with Characteristic Shapes from Escherichia coli. by Zimmerman SB, Murphy LD.; 2001 Sep 1; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=95379

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Repair of DNA Lesions Induced by Hydrogen Peroxide in the Presence of Iron Chelators in Escherichia coli: Participation of Endonuclease IV and Fpg. by Galhardo RS, Almeida CE, Leitao AC, Cabral-Neto JB.; 2000 Apr 1; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=101895

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Repair System for Noncanonical Purines in Escherichia coli. by Burgis NE, Brucker JJ, Cunningham RP.; 2003 May; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=154070

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Representational Difference Analysis between Afa/Dr Diffusely Adhering Escherichia coli and Nonpathogenic E. coli K-12. by Blanc-Potard AB, Tinsley C, Scaletsky I, Le Bouguenec C, Guignot J, Servin AL, Nassif X, Bernet-Camard MF.; 2002 Oct; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=128352

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Restriction-Site-Specific PCR as a Rapid Test To Detect Enterohemorrhagic Escherichia coli O157:H7 Strains in Environmental Samples. by Kimura R, Mandrell RE, Galland JC, Hyatt D, Riley LW.; 2000 Jun; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=110571

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Ribose catabolism of Escherichia coli: characterization of the rpiB gene encoding ribose phosphate isomerase B and of the rpiR gene, which is involved in regulation of rpiB expression. by Sorensen KI, Hove-Jensen B.; 1996 Feb; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&rendertype=abstr act&artid=177759

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Risk Factors for Antibiotic-Resistant Escherichia coli Isolated from Hospitalized Patients with Urinary Tract Infections: a Prospective Study. by Sotto A, De Boever CM, Fabbro-Peray P, Gouby A, Sirot D, Jourdan J.; 2001 Feb; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=87756

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RNA degradosomes exist in vivo in Escherichia coli as multicomponent complexes associated with the cytoplasmic membrane via the N-terminal region of ribonuclease E. by Liou GG, Jane WN, Cohen SN, Lin NS, Lin-Chao S.; 2001 Jan 2; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=14545

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Role for a Phage Promoter in Shiga Toxin 2 Expression from a Pathogenic Escherichia coli Strain. by Wagner PL, Neely MN, Zhang X, Acheson DW, Waldor MK, Friedman DI.; 2001 Mar 15; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=95105

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Role of BfpF, a Member of the PilT Family of Putative Nucleotide-Binding Proteins, in Type IV Pilus Biogenesis and in Interactions between Enteropathogenic Escherichia coli and Host Cells. by Anantha RP, Stone KD, Donnenberg MS.; 1998 Jan; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=107867

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Role of DnaB Helicase in UV-Induced Illegitimate Recombination in Escherichia coli. by Hanada K, Yamashita T, Shobuike Y, Ikeda H.; 2001 Sep 1; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=95370

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Role of Escherichia coli Nitrogen Regulatory Genes in the Nitrogen Response of the Azotobacter vinelandii NifL-NifA Complex. by Reyes-Ramirez F, Little R, Dixon R.; 2001 May 15; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=95207

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Role of Region C in Regulation of the Heat Shock Gene-Specific Sigma Factor of Escherichia coli, [final sigma]32. by Arsene F, Tomoyasu T, Mogk A, Schirra C, Schulze-Specking A, Bukau B.; 1999 Jun 1; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=93824

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Role of rpoS in Acid Resistance and Fecal Shedding of Escherichia coli O157:H7. by Price SB, Cheng CM, Kaspar CW, Wright JC, DeGraves FJ, Penfound TA, CastanieCornet MP, Foster JW.; 2000 Feb; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=91873

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Role of the Carboxy Terminus of Escherichia coli FtsA in Self-Interaction and Cell Division. by Yim L, Vandenbussche G, Mingorance J, Rueda S, Casanova M, Ruysschaert JM, Vicente M.; 2000 Nov 15; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=94782

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Role of the Escherichia coli O157:H7 O side chain in adherence and analysis of an rfb locus. by Bilge SS, Vary JC Jr, Dowell SF, Tarr PI.; 1996 Nov; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&rendertype=abstr act&artid=174447

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rpoS Gene Function Is a Disadvantage for Escherichia coli BJ4 during Competitive Colonization of the Mouse Large Intestine. by Krogfelt KA, Hjulgaard M, Sorensen K, Cohen PS, Givskov M.; 2000 May; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=97454

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Search for Cytolethal Distending Toxin Production among Fecal Escherichia Coli Isolates from Brazilian Children with Diarrhea and without Diarrhea. by Marques LR, Tavechio AT, Abe CM, Gomes TA.; 2003 May; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=154697

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Secretion of extracellular proteins by enterohemorrhagic Escherichia coli via a putative type III secretion system. by Jarvis KG, Kaper JB.; 1996 Nov; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&rendertype=abstr act&artid=174451

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Selective and Sensitive Method for PCR Amplification of Escherichia coli 16S rRNA Genes in Soil. by Sabat G, Rose P, Hickey WJ, Harkin JM.; 2000 Feb; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=91908

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Selective Isolation of eae-Positive Strains of Shiga Toxin-Producing Escherichia coli. by Fukushima H, Hoshina K, Gomyoda M.; 2000 Apr; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=86528

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Sensitivities and Specificities of Premier E. coli O157 and Premier EHEC Enzyme Immunoassays for Diagnosis of Infection with Verotoxin (Shiga-Like Toxin)Producing Escherichia coli. by Mackenzie AM, Lebel P, Orrbine E, Rowe PC, Hyde L, Chan F, Johnson W, McLaine PN.; 1998 Jun; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=104886

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Sequence Diversity of Flagellin (fliC) Alleles in Pathogenic Escherichia coli. by Reid SD, Selander RK, Whittam TS.; 1999 Jan 1; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=103544

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Sequence Diversity of the Escherichia coli H7 fliC Genes: Implication for a DNABased Typing Scheme for E. coli O157:H7. by Wang L, Rothemund D, Curd H, Reeves PR.; 2000 May; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=86588

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Sequence of Shiga Toxin 2 Phage 933W from Escherichia coli O157:H7: Shiga Toxin as a Phage Late-Gene Product. by Plunkett G III, Rose DJ, Durfee TJ, Blattner FR.; 1999 Mar 15; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=93574

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Sequencing of Escherichia coli O111 O-Antigen Gene Cluster and Identification of O111-Specific Genes. by Wang L, Curd H, Qu W, Reeves PR.; 1998 Nov; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=105298

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Serotypes, Virulence Genes, and Intimin Types of Shiga Toxin (Verotoxin)-Producing Escherichia coli Isolates from Healthy Sheep in Spain. by Blanco M, Blanco JE, Mora

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A, Rey J, Alonso JM, Hermoso M, Hermoso J, Alonso MP, Dahbi G, Gonzalez EA, Bernardez MI, Blanco J.; 2003 Apr; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=153932 •

sfi-independent filamentation in Escherichia coli Is lexA dependent and requires DNA damage for induction. by Hill TM, Sharma B, Valjavec-Gratian M, Smith J.; 1997 Mar; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&rendertype=abstr act&artid=178916

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Shedding of Escherichia coli O157:H7 in Dairy Cattle Housed in a Confined Environment following Waterborne Inoculation. by Shere JA, Kaspar CW, Bartlett KJ, Linden SE, Norell B, Francey S, Schaefer DM.; 2002 Apr; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=123869

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Shiga Toxin-Producing Escherichia coli Infection and Antibodies against Stx2 and Stx1 in Household Contacts of Children with Enteropathic Hemolytic-Uremic Syndrome. by Ludwig K, Sarkim V, Bitzan M, Karmali MA, Bobrowski C, Ruder H, Laufs R, Sobottka I, Petric M, Karch H, Muller-Wiefel DE.; 2002 May; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=130915

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Simultaneous Detection and Differentiation of Escherichia coli Populations from Environmental Freshwaters by Means of Sequence Variations in a Fragment of the [beta]-d-Glucuronidase Gene. by Farnleitner AH, Kreuzinger N, Kavka GG, Grillenberger S, Rath J, Mach RL.; 2000 Apr; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=91990

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Simultaneous Detection of Salmonella Strains and Escherichia coli O157:H7 with Fluorogenic PCR and Single-Enrichment-Broth Culture. by Sharma VK, Carlson SA.; 2000 Dec; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=92484

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Sorbitol-Fermenting Shiga Toxin-Producing Escherichia coli O157:H[minus sign] Strains: Epidemiology, Phenotypic and Molecular Characteristics, and Microbiological Diagnosis. by Karch H, Bielaszewska M.; 2001 Jun; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=88086

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Specific Adhesion to Cellulose and Hydrolysis of Organophosphate Nerve Agents by a Genetically Engineered Escherichia coli Strain with a Surface-Expressed CelluloseBinding Domain and Organophosphorus Hydrolase. by Wang AA, Mulchandani A, Chen W.; 2002 Apr; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=123835

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Specific interaction between the ribosome recycling factor and the elongation factorG from Mycobacterium tuberculosis mediates peptidyl-tRNA release and ribosome recycling in Escherichia coli. by Rao AR, Varshney U.; 2001 Jun 1; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=125489

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Specific Secretion of Active Single-Chain Fv Antibodies into the Supernatants of Escherichia coli Cultures by Use of the Hemolysin System. by Fernandez LA, Sola I, Enjuanes L, de Lorenzo V.; 2000 Nov; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=92415

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Starvation- and stationary-phase-induced acid tolerance in Escherichia coli O157:H7. by Arnold KW, Kaspar CW.; 1995 May; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&rendertype=abstr act&artid=167472

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Structure-Function Relationship of Antibacterial Synthetic Peptides Homologous to a Helical Surface Region on Human Lactoferrin against Escherichia coli Serotype O111. by Chapple DS, Mason DJ, Joannou CL, Odell EW, Gant V, Evans RW.; 1998 Jun; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=108221

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Stx2 Subtyping of Shiga Toxin-Producing Escherichia coli Isolated from Cattle in France: Detection of a New Stx2 Subtype and Correlation with Additional Virulence Factors. by Bertin Y, Boukhors K, Pradel N, Livrelli V, Martin C.; 2001 Sep; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=88297

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Substrate Specificity of the RND-Type Multidrug Efflux Pumps AcrB and AcrD of Escherichia coli Is Determined Predominately by Two Large Periplasmic Loops. by Elkins CA, Nikaido H.; 2002 Dec; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=135441

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Supermolecular structure of the enteropathogenic Escherichia coli type III secretion system and its direct interaction with the EspA-sheath-like structure. by Sekiya K, Ohishi M, Ogino T, Tamano K, Sasakawa C, Abe A.; 2001 Sep 25; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=58782

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Suppression of Hypersensitivity of Escherichia coli acrB Mutant to Organic Solvents by Integrational Activation of the acrEF Operon with the IS1 or IS2 Element. by Kobayashi K, Tsukagoshi N, Aono R.; 2001 Apr 15; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=95182

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Survey of Extended-Spectrum [beta]-Lactamases in Clinical Isolates of Escherichia coli and Klebsiella pneumoniae: Prevalence of TEM-52 in Korea. by Pai H, Lyu S, Lee JH, Kim J, Kwon Y, Kim JW, Choe KW.; 1999 Jun; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=84943

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The ATP-Dependent HslVU/ClpQY Protease Participates in Turnover of Cell Division Inhibitor SulA in Escherichia coli. by Kanemori M, Yanagi H, Yura T.; 1999 Jun 15; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=93843

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The Cellular Form of Human Fibronectin as an Adhesion Target for the S Fimbriae of Meningitis-Associated Escherichia coli. by Saren A, Virkola R, Hacker J, Korhonen TK.; 1999 May; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=116024

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The Chromosomal Arsenic Resistance Genes of Thiobacillus ferrooxidans Have an Unusual Arrangement and Confer Increased Arsenic and Antimony Resistance to Escherichia coli. by Butcher BG, Deane SM, Rawlings DE.; 2000 May; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=101419

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The Cloned Locus of Enterocyte Effacement from Enterohemorrhagic Escherichia coli O157:H7 Is Unable To Confer the Attaching and Effacing Phenotype upon E. coli K12. by Elliott SJ, Yu J, Kaper JB.; 1999 Aug; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=96734

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The efficiency of Escherichia coli selenocysteine insertion is influenced by the immediate downstream nucleotide. by Sandman KE, Noren CJ.; 2000 Feb 1; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=102542

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The Escherichia coli glucose transporter enzyme IICBGlc recruits the global repressor Mlc. by Nam TW, Cho SH, Shin D, Kim JH, Jeong JY, Lee JH, Roe JH, Peterkofsky A, Kang SO, Ryu S, Seok YJ.; 2001 Feb 1; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=133465

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The Escherichia coli mazEF Suicide Module Mediates Thymineless Death. by Sat B, Reches M, Engelberg-Kulka H.; 2003 Mar; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=150121

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The EspD Protein of Enterohemorrhagic Escherichia coli Is Required for the Formation of Bacterial Surface Appendages and Is Incorporated in the Cytoplasmic Membranes of Target Cells. by Kresse AU, Rohde M, Guzman CA.; 1999 Sep; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=96816

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The Flavoenzyme Ferredoxin (Flavodoxin)-NADP(H) Reductase Modulates NADP(H) Homeostasis during the soxRS Response of Escherichia coli. by Krapp AR, Rodriguez RE, Poli HO, Paladini DH, Palatnik JF, Carrillo N.; 2002 Mar; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=134851

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The Gene Locus yijP Contributes to Escherichia coli K1 Invasion of Brain Microvascular Endothelial Cells. by Wang Y, Huang SH, Wass CA, Stins MF, Kim KS.; 1999 Sep; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=96805

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The Link between Phylogeny and Virulence in Escherichia coli Extraintestinal Infection. by Picard B, Garcia JS, Gouriou S, Duriez P, Brahimi N, Bingen E, Elion J, Denamur E.; 1999 Feb; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=96353

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The nac (Nitrogen Assimilation Control) Gene from Escherichia coli. by Muse WB, Bender RA.; 1998 Mar 1; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=107004

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The ompB Operon Partially Determines Differential Expression of OmpC in Salmonella typhi and Escherichia coli. by Martinez-Flores I, Cano R, Bustamante VH, Calva E, Puente JL.; 1999 Jan 15; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=93410

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The PalkBFGHJKL Promoter Is under Carbon Catabolite Repression Control in Pseudomonas oleovorans but Not in Escherichia coli alk + Recombinants. by Staijen IE, Marcionelli R, Witholt B.; 1999 Mar 1; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=93552

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The Periplasmic Murein Peptide-Binding Protein MppA Is a Negative Regulator of Multiple Antibiotic Resistance in Escherichia coli. by Li H, Park JT.; 1999 Aug 15; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=93970

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The Wzz (Cld) Protein in Escherichia coli: Amino Acid Sequence Variation Determines O-Antigen Chain Length Specificity. by Franco AV, Liu D, Reeves PR.; 1998 May 15; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=107218

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The yhhP Gene Encoding a Small Ubiquitous Protein Is Fundamental for Normal Cell Growth of Escherichia coli. by Yamashino T, Isomura M, Ueguchi C, Mizuno T.; 1998 Apr 15; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=107159

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The yiaE Gene, Located at 80.1 Minutes on the Escherichia coli Chromosome, Encodes a 2-Ketoaldonate Reductase. by Yum DY, Lee BY, Hahm DH, Pan JG.; 1998 Nov 15; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=107674

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Thirteen Years of Building Constraint-Based In Silico Models of Escherichia coli. by Reed JL, Palsson BO.; 2003 May; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=154396

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Three members of a novel small gene-family from Arabidopsis thaliana able to complement functionally an Escherichia coli mutant defective in PAPS reductase activity encode proteins with a thioredoxin-like domain and "APS reductase" activity. by Gutierrez-Marcos JF, Roberts MA, Campbell EI, Wray JL.; 1996 Nov 12; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=24101

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Timing of FtsZ Assembly in Escherichia coli. by Den Blaauwen T, Buddelmeijer N, Aarsman ME, Hameete CM, Nanninga N.; 1999 Sep 1; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=94019

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TLA-1: a New Plasmid-Mediated Extended-Spectrum [beta]-Lactamase from Escherichia coli. by Silva J, Aguilar C, Ayala G, Estrada MA, Garza-Ramos U, LaraLemus R, Ledezma L.; 2000 Apr; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=89804

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TonB-Dependent Systems of Uropathogenic Escherichia coli: Aerobactin and Heme Transport and TonB Are Required for Virulence in the Mouse. by Torres AG, Redford P, Welch RA, Payne SM.; 2001 Oct; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=98749

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Transcriptional Analysis of Essential Genes of the Escherichia coli Fatty Acid Biosynthesis Gene Cluster by Functional Replacement with the Analogous Salmonella typhimurium Gene Cluster. by Zhang Y, Cronan JE Jr.; 1998 Jul 1; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=107281

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Transcriptional Analysis of the sfa Determinant Revealing Multiple mRNA Processing Events in the Biogenesis of S Fimbriae in Pathogenic Escherichia coli. by Balsalobre C, Morschhauser J, Jass J, Hacker J, Uhlin BE.; 2003 Jan; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=145322

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Transcriptional Regulation of the esp Genes of Enterohemorrhagic Escherichia coli. by Beltrametti F, Kresse AU, Guzman CA.; 1999 Jun 1; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=93807

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Transduction of Enteric Escherichia coli Isolates with a Derivative of Shiga Toxin 2Encoding Bacteriophage [phi]3538 Isolated from Escherichia coli O157:H7. by Schmidt H, Bielaszewska M, Karch H.; 1999 Sep; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=99711

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Type 1 Fimbriation and Its Phase Switching in Diarrheagenic Escherichia coli Strains. by Iida KI, Mizunoe Y, Wai SN, Yoshida SI.; 2001 May; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=96088

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Type-Specific Contributions to Chromosome Size Differences in Escherichia coli. by Rode CK, Melkerson-Watson LJ, Johnson AT, Bloch CA.; 1999 Jan; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=96301

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Typing of Intimin Genes in Human and Animal Enterohemorrhagic and Enteropathogenic Escherichia coli: Characterization of a New Intimin Variant. by Oswald E, Schmidt H, Morabito S, Karch H, Marches O, Caprioli A.; 2000 Jan; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=97102

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Urease of Enterohemorrhagic Escherichia coli: Evidence for Regulation by Fur and a trans-Acting Factor. by Heimer SR, Welch RA, Perna NT, Posfai G, Evans PS, Kaper JB, Blattner FR, Mobley HL.; 2002 Feb; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=127683

102 E. coli

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Use of Bacteriophage [lambda] Recombination Functions To Promote Gene Replacement in Escherichia coli. by Murphy KC.; 1998 Apr 15; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=107131

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Use of heme and hemoglobin by Escherichia coli O157 and other Shiga-like-toxinproducing E. coli serogroups. by Law D, Kelly J.; 1995 Feb; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&rendertype=abstr act&artid=173054

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Use of Repetitive DNA Sequences and the PCR To Differentiate Escherichia coli Isolates from Human and Animal Sources. by Dombek PE, Johnson LK, Zimmerley ST, Sadowsky MJ.; 2000 Jun; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=110583

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Use of the flagellar H7 gene as a target in multiplex PCR assays and improved specificity in identification of enterohemorrhagic Escherichia coli strains. by Gannon VP, D'Souza S, Graham T, King RK, Rahn K, Read S.; 1997 Mar; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&rendertype=abstr act&artid=229645

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UV-induced crosslinks in the 16S rRNAs of Escherichia coli, Bacillus subtilis and Thermus aquaticus and their implications for ribosome structure and photochemistry. by Noah JW, Shapkina T, Wollenzien P.; 2000 Oct 1; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=110760

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Variation in Resistance to High Hydrostatic Pressure and rpoS Heterogeneity in Natural Isolates of Escherichia coli O157:H7. by Robey M, Benito A, Hutson RH, Pascual C, Park SF, Mackey BM.; 2001 Oct; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=93247

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Variations in the csgD Promoter of Escherichia coli O157:H7 Associated with Increased Virulence in Mice and Increased Invasion of HEp-2 Cells. by Uhlich GA, Keen JE, Elder RO.; 2002 Jan; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=127602

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Viability of an Escherichia coli pgsA Null Mutant Lacking Detectable Phosphatidylglycerol and Cardiolipin. by Kikuchi S, Shibuya I, Matsumoto K.; 2000 Jan 15; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=94285

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Virulence Markers of Enteroaggregative Escherichia coli Isolated from Children and Adults with Diarrhea in Brasilia, Brazil. by Piva IC, Pereira AL, Ferraz LR, Silva RS, Vieira AC, Blanco JE, Blanco M, Blanco J, Giugliano LG.; 2003 May; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=154701

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Virulence Properties of Escherichia coli 83972, a Prototype Strain Associated with Asymptomatic Bacteriuria. by Hull RA, Rudy DC, Donovan WH, Wieser IE, Stewart C, Darouiche RO.; 1999 Jan; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=96330

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Virulence Properties of Shiga Toxin-Producing Escherichia coli (STEC) Strains of Serogroup O118, a Major Group of STEC Pathogens in Calves. by Wieler LH, Schwanitz A, Vieler E, Busse B, Steinruck H, Kaper JB, Baljer G.; 1998 Jun; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=104885

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YfcX Enables Medium-Chain-Length Poly(3-Hydroxyalkanoate) Formation from Fatty Acids in Recombinant Escherichia coli fadB Strains. by Snell KD, Feng F, Zhong L, Martin D, Madison LL.; 2002 Oct; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=139608

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ZitB (YbgR), a Member of the Cation Diffusion Facilitator Family, Is an Additional Zinc Transporter in Escherichia coli. by Grass G, Fan B, Rosen BP, Franke S, Nies DH, Rensing C.; 2001 Aug 1; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=95364

The National Library of Medicine: PubMed One of the quickest and most comprehensive ways to find academic studies in both English and other languages is to use PubMed, maintained by the National Library of Medicine.6 The advantage of PubMed over previously mentioned sources is that it covers a greater number of domestic and foreign references. It is also free to use. If the publisher has a Web site that offers full text of its journals, PubMed will provide links to that site, as well as to sites offering other related data. User registration, a subscription fee, or some other type of fee may be required to access the full text of articles in some journals. To generate your own bibliography of studies dealing with E. coli, simply go to the PubMed Web site at http://www.ncbi.nlm.nih.gov/pubmed. Type “E. coli” (or synonyms) into the search box, and click “Go.” The following is the type of output you can expect from PubMed for E. coli (hyperlinks lead to article summaries): •

A novel poxvirus gene and its human homolog are similar to an E. coli lysophospholipase. Author(s): Wall EM, Cao J, Chen N, Buller RM, Upton C. Source: Virus Research. 1997 December; 52(2): 157-67. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=9495531&dopt=Abstract

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A recombinant human G-CSF/GM-CSF fusion protein from E. coli showing colony stimulating activity on human bone marrow cells. Author(s): Lee AY, Chung HK, Bae EK, Hwang JS, Sung BW, Cho CW, Kim JK, Lee K, Han JY, Lee CT, Youn HJ. Source: Biotechnology Letters. 2003 February; 25(3): 205-11. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12882572&dopt=Abstract

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A tangled tale of E. coli virulence. Author(s): Weidenbach K. Source: Science. 1998 June 26; 280(5372): 2048. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=9669959&dopt=Abstract

6

PubMed was developed by the National Center for Biotechnology Information (NCBI) at the National Library of Medicine (NLM) at the National Institutes of Health (NIH). The PubMed database was developed in conjunction with publishers of biomedical literature as a search tool for accessing literature citations and linking to full-text journal articles at Web sites of participating publishers. Publishers that participate in PubMed supply NLM with their citations electronically prior to or at the time of publication.

104 E. coli

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Activation of Helicobacter pylori ureA promoter by a hybrid Escherichia coli-H. pylori rpoD gene in E. coli. Author(s): Shirai M, Fujinaga R, Akada JK, Nakazawa T. Source: Gene. 1999 November 1; 239(2): 351-9. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10548737&dopt=Abstract

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Acute gastroenteritis caused by E. coli O.157:H7 in Pakistani children. Author(s): Mufti P, Bhutta ZA, Hasan R. Source: Journal of Tropical Pediatrics. 1999 August; 45(4): 253-4. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10467843&dopt=Abstract

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Adherent-invasive Escherichia coli: a putative new E. coli pathotype associated with Crohn's disease. Author(s): Darfeuille-Michaud A. Source: International Journal of Medical Microbiology : Ijmm. 2002 September; 292(3-4): 185-93. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12398209&dopt=Abstract

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Advances in refolding of proteins produced in E. coli. Author(s): Lilie H, Schwarz E, Rudolph R. Source: Current Opinion in Biotechnology. 1998 October; 9(5): 497-501. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=9821278&dopt=Abstract

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AID mutates E. coli suggesting a DNA deamination mechanism for antibody diversification. Author(s): Petersen-Mahrt SK, Harris RS, Neuberger MS. Source: Nature. 2002 July 4; 418(6893): 99-103. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12097915&dopt=Abstract

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Alkylation resistance of E. coli cells expressing different isoforms of human alkyladenine DNA glycosylase (hAAG). Author(s): Bonanno K, Wyrzykowski J, Chong W, Matijasevic Z, Volkert MR. Source: Dna Repair. 2002 July 17; 1(7): 507-16. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12509225&dopt=Abstract

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Alpha-haemolysin of uropathogenic E. coli induces Ca2+ oscillations in renal epithelial cells. Author(s): Uhlen P, Laestadius A, Jahnukainen T, Soderblom T, Backhed F, Celsi G, Brismar H, Normark S, Aperia A, Richter-Dahlfors A. Source: Nature. 2000 June 8; 405(6787): 694-7. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10864327&dopt=Abstract

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An Escherichia coli reference collection group B2- and uropathogen-associated polymorphism in the rpoS-mutS region of the E. coli chromosome. Author(s): Culham DE, Wood JM. Source: Journal of Bacteriology. 2000 November; 182(21): 6272-6. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11029456&dopt=Abstract

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An improved procedure for production of human epidermal growth factor from recombinant E. coli. Author(s): Tong WY, Yao SJ, Zhu ZQ, Yu J. Source: Applied Microbiology and Biotechnology. 2001 December; 57(5-6): 674-9. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11778877&dopt=Abstract

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An outbreak of gastroenteritis in Osaka, Japan due to Escherichia coli serogroup O166:H15 that had a coding gene for enteroaggregative E. coli heat-stable enterotoxin 1 (EAST1). Author(s): Zhou Z, Ogasawara J, Nishikawa Y, Seto Y, Helander A, Hase A, Iritani N, Nakamura H, Arikawa K, Kai A, Kamata Y, Hoshi H, Haruki K. Source: Epidemiology and Infection. 2002 June; 128(3): 363-71. Erratum In: Epidemiol Infect. 2002 December; 129(3): 689. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12113479&dopt=Abstract

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Analysis of saliva for antibodies to the LPS of Escherichia coli O157 in patients with serum antibodies to E. coli O157 LPS. Author(s): Chart H, Perry NT, Willshaw GA, Cheasty T. Source: Journal of Medical Microbiology. 2003 July; 52(Pt 7): 569-72. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12808078&dopt=Abstract

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Anti-asparaginase antibodies following E. coli asparaginase therapy in pediatric acute lymphoblastic leukemia. Author(s): Woo MH, Hak LJ, Storm MC, Evans WE, Sandlund JT, Rivera GK, Wang B, Pui CH, Relling MV. Source: Leukemia : Official Journal of the Leukemia Society of America, Leukemia Research Fund, U.K. 1998 October; 12(10): 1527-33. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=9766495&dopt=Abstract

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Antibiotic resistance of E. coli in sewage and sludge. Author(s): Reinthaler FF, Posch J, Feierl G, Wust G, Haas D, Ruckenbauer G, Mascher F, Marth E. Source: Water Research. 2003 April; 37(8): 1685-90. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12697213&dopt=Abstract

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Antibodies against the COOH-terminal region of E. coli ClpP protease in patients with primary biliary cirrhosis. Author(s): Mayo I, Arizti P, Pares A, Oliva J, Doforno RA, de Sagarra MR, Rodes J, Castano JG. Source: Journal of Hepatology. 2000 October; 33(4): 528-36. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11059856&dopt=Abstract

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Antimotility agents and E. coli infection. Author(s): Tarr PI, Christie DL. Source: Cmaj : Canadian Medical Association Journal = Journal De L'association Medicale Canadienne. 1999 April 6; 160(7): 984, 986. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10207332&dopt=Abstract

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Association between hemolytic uremic syndrome and verotoxin-producing strains of E. coli. Author(s): Jure MA, de Saab OA, de Castillo MC, Sesma F, Miceli S, Zamora AM, de Ruiz Holgado AP, de Nader OM. Source: Rev Latinoam Microbiol. 1998 January-June; 40(1-2): 1-8. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10932728&dopt=Abstract

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ATPase and GTPase activities copurifying with GTP-binding proteins in E. coli. Author(s): Sayed A, Matsuyama S, Inoue K, Alsina J, Cai F, Chen J, Inouye M. Source: J Mol Microbiol Biotechnol. 2000 July; 2(3): 261-3. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10937433&dopt=Abstract

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Bacteria and endotoxin induce release of basophil histamine in patients with atopic dermatitis. In vitro experiments with S. aureus, teichoic acid, E. coli and E. coli LPS. Author(s): Jorgensen J, Bach-Mortensen N, Koch C, Fomsgaard A, Baek L, Jarlov JO, Espersen F, Jensen CB, Skov PS, Norn S. Source: Allergy. 1987 July; 42(5): 395-7. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=2443036&dopt=Abstract

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Bacterial lipopolysaccharides and glutathione mixed disulfides as possible contaminants of human growth hormone produced with the use of E. coli K12. Author(s): Axelsson K. Source: Acta Chem Scand B. 1985; 39(1): 69-77. No Abstract Available. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=3885661&dopt=Abstract

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Bacteriological and clinical studies in infantile diarrhoea. I. Known pathogens: Shigella, Salmonella and enteropathogenic E. coli. Author(s): Mohiedin MS, Gabr M, el-Hefny A, Sayed-Mahmoud S, Abdallah A. Source: J Trop Pediatr Afr Child Health. 1965 December; 11(3): 69-78. No Abstract Available. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=5321931&dopt=Abstract

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Bcl-2 antiapoptotic protein mediates verotoxin II-induced cell death: possible association between bcl-2 and tissue failure by E. coli O157:H7. Author(s): Suzuki A, Doi H, Matsuzawa F, Aikawa S, Takiguchi K, Kawano H, Hayashida M, Ohno S. Source: Genes & Development. 2000 July 15; 14(14): 1734-40. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10898788&dopt=Abstract

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Better red than dead. An inexpensive new test instantly spots harmful E. coli. Author(s): Zorpette G. Source: Scientific American. 1997 March; 276(3): 36. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=9046109&dopt=Abstract

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Bilateral brachial plexopathy after E. coli sepsis. Author(s): Tzur A, Shahin R. Source: Isr J Med Sci. 1997 October; 33(10): 687-9. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=9397145&dopt=Abstract

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Binding of cloned S-fimbriated E. coli to human buccal epithelial cells--different inhibition of binding by neonatal saliva and adult saliva. Author(s): Schroten H, Wolske A, Plogmann R, Hanisch FG, Hacker J, Uhlenbruck G, Wahn V. Source: Zentralbl Bakteriol. 1991 January; 274(4): 514-8. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=1713767&dopt=Abstract

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Binding of E. coli to human blood leukocytes. Author(s): Guan YZ, Kharazmi A. Source: Apmis : Acta Pathologica, Microbiologica, Et Immunologica Scandinavica. 1988 December; 96(12): 1061-5. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=3063302&dopt=Abstract

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Binding of phosphate and sulfate anions by purine nucleoside phosphorylase from E. coli: ligand-dependent quenching of enzyme intrinsic fluorescence. Author(s): Kierdaszuk B, Modrak-Wojcik A, Shugar D. Source: Biophysical Chemistry. 1997 January 31; 63(2-3): 107-18. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=9108686&dopt=Abstract

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Binding of the anticancer drug ZD1694 to E. coli thymidylate synthase: assessing specificity and affinity. Author(s): Rutenber EE, Stroud RM. Source: Structure (London, England). 1996 November 15; 4(11): 1317-24. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=8939755&dopt=Abstract

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Binding properties and solubility of single-chain T cell receptors expressed in E. coli. Author(s): Schodin BA, Schlueter CJ, Kranz DM. Source: Molecular Immunology. 1996 June; 33(9): 819-29. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=8811077&dopt=Abstract

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Binding to and killing of human renal epithelial cells by hemolytic P-fimbriated E. coli. Author(s): Trifillis AL, Donnenberg MS, Cui X, Russell RG, Utsalo SJ, Mobley HL, Warren JW. Source: Kidney International. 1994 October; 46(4): 1083-91. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=7861702&dopt=Abstract

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Biological activities of recombinant human IFN-beta 2/IL-6 (E. coli). Author(s): Revel M, Zilberstein A, Chen L, Gothelf Y, Barash I, Novick D, Rubinstein M, Michalevicz R. Source: Annals of the New York Academy of Sciences. 1989; 557: 144-55, Discussion 156. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=2660694&dopt=Abstract

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Biophysical analysis of the interaction of human ifnar2 expressed in E. coli with IFNalpha2. Author(s): Piehler J, Schreiber G. Source: Journal of Molecular Biology. 1999 May 28; 289(1): 57-67. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10339405&dopt=Abstract

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BipA affects Ca++ fluxes and phosphorylation of the translocated intimin receptor (Tir/Hp90) in host epithelial cells infected with enteropathogenic E. coli. Author(s): Farris M, Grant A, Jane S, Chad J, O'Connor CD. Source: Biochemical Society Transactions. 1998 August; 26(3): S225. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=9765944&dopt=Abstract

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Bovine colostrum ameliorates diarrhea in infection with diarrheagenic Escherichia coli, shiga toxin-producing E. coli, and E. coli expressing intimin and hemolysin. Author(s): Huppertz HI, Rutkowski S, Busch DH, Eisebit R, Lissner R, Karch H. Source: Journal of Pediatric Gastroenterology and Nutrition. 1999 October; 29(4): 452-6. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10512407&dopt=Abstract

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Bovine milk antibodies in the treatment of enteric infections and their ability to eliminate virulence factors from pathogenic E. coli. Author(s): Pahud JJ, Hilpert H, Schwarz K, Amster H, Smiley M. Source: Advances in Experimental Medicine and Biology. 1981; 137: 591-600. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=7036687&dopt=Abstract

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Breast feeding and biological properties of faecal E. coli strains. Author(s): Gothefors L, Olling S, Winberg J. Source: Acta Paediatr Scand. 1975 November; 64(6): 807-12. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=1103565&dopt=Abstract

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Breast feeding and incidence of E. coli infections in newborn nurseries. Author(s): Jelliffe EF, Overoll JC Jr, Headings DL. Source: The Journal of Pediatrics. 1977 June; 90(6): 1038-9. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=323445&dopt=Abstract

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Canadian integrated surveillance report: Salmonella, Campylobacter, pathogenic E. coli and Shigella, from 1996 to 1999. Author(s): Bowman C, Flint J, Pollari F. Source: Can Commun Dis Rep. 2003 March; 29 Suppl 1: I-Vi, 1-32 (Eng); I-Vi, 1-34 (Fre). English, French. No Abstract Available. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12793118&dopt=Abstract

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Carbohydrate-deficient glycoprotein syndrome type 1A: expression and characterisation of wild type and mutant PMM2 in E. coli. Author(s): Kjaergaard S, Skovby F, Schwartz M. Source: European Journal of Human Genetics : Ejhg. 1999 December; 7(8): 884-8. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10602363&dopt=Abstract

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Cell-density dependent effects of low-dose ionizing radiation on E. coli cells. Author(s): Alipov ED, Shcheglov VS, Sarimov RM, Belyaev IY. Source: Radiats Biol Radioecol. 2003 March-April; 43(2): 167-71. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12754801&dopt=Abstract

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Cell-surface attachment of pedestal-forming enteropathogenic E. coli induces a clustering of raft components and a recruitment of annexin 2. Author(s): Zobiack N, Rescher U, Laarmann S, Michgehl S, Schmidt MA, Gerke V. Source: Journal of Cell Science. 2002 January 1; 115(Pt 1): 91-8. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11801727&dopt=Abstract

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Characterization and diagnostic potential of hepatitis B virus nucleocapsid expressed in E. coli and P. pastoris. Author(s): Watelet B, Quibriac M, Rolland D, Gervasi G, Gauthier M, Jolivet M, Letourneur O. Source: Journal of Virological Methods. 2002 January; 99(1-2): 99-114. Corrected and Republished In: http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11684308&dopt=Abstract

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Characterization of dendritic cells generated in vivo by an E. coli derived chimeric dual receptor agonist. Author(s): Kahn LE, Doshi PD, McGarity KL, Yu M, Bono CP, Lie WR, Rankin AM, Smidt ML, Streeter PR, Klein BK, Welply JK, Woulfe SL. Source: Medical Science Monitor : International Medical Journal of Experimental and Clinical Research. 2002 December; 8(12): Br504-14. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12503028&dopt=Abstract

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Characterization of expanded-spectrum cephalosporin resistance in E. coli isolates associated with bovine calf diarrhoeal disease. Author(s): Bradford PA, Petersen PJ, Fingerman IM, White DG. Source: The Journal of Antimicrobial Chemotherapy. 1999 November; 44(5): 607-10. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10552976&dopt=Abstract

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Cloning and characterization of genes encoding homologues of the B subunit of cholera toxin and the Escherichia coli heat-labile enterotoxin from clinical isolates of Citrobacter freundii and E. coli. Author(s): Karasawa T, Ito H, Tsukamoto T, Yamasaki S, Kurazono H, Faruque SM, Nair GB, Nishibuchi M, Takeda Y. Source: Infection and Immunity. 2002 December; 70(12): 7153-5. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12438400&dopt=Abstract

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Commentary on: Dou C, Bournique J, Zinda M, Gnezda M, Nally A, Salamone S. Comparison of rates of hydrolysis of lorazepam-glucuronide, oxazepam-glucuronide and temazepam-glucuronide catalyzed by E. coli beta-glucuronidase using the on-line benzodiazepine screening immunoassay on the Roche/Hitachi 917 analyzer. Author(s): O'Neal CL, Poklis A. Source: J Forensic Sci. 2002 March; 47(2): 427-8. No Abstract Available. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11908630&dopt=Abstract

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Comparative study of the coupling between topoisomerase I activity and highmobility group proteins in E. coli and mammalian cells. Author(s): Veilleux S, Caron N, Boissonneault G. Source: Dna and Cell Biology. 2000 July; 19(7): 421-9. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10945232&dopt=Abstract

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Comparative study on the biological properties of 2',5'-oligoadenylate derivatives with purified human RNase L expressed in E. coli. Author(s): Yoshimura A, Nakanishi M, Yatome C, Kitade Y. Source: Journal of Biochemistry. 2002 October; 132(4): 643-8. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12359081&dopt=Abstract

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Comparison of an immunochromatographic method and the TaqMan E. coli O157:H7 assay for detection of Escherichia coli O157:H7 in alfalfa sprout spent irrigation water and in sprouts after blanching. Author(s): J Virol Methods. 2002 Apr;102(1-2):175-90 Source: Journal of Industrial Microbiology & Biotechnology. 2001 August; 27(2): 129-34. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11879706

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Comparison of techniques for monitoring antibody fragment production in E. coli fermentation cultures. Author(s): Bowering LC, Bracewell DG, Kesharvarz-Moore E, Hoare M, Weir AN. Source: Biotechnology Progress. 2002 November-December; 18(6): 1431-8. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12467481&dopt=Abstract

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Complement-mediated bactericidal activity of human milk to a serum-susceptible strain of E. coli 0111. Author(s): Ogundele MO. Source: Journal of Applied Microbiology. 1999 November; 87(5): 689-96. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10594709&dopt=Abstract

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Concentrating rotavirus and recombinant-enhanced green fluorescent protein from E. coli using a pH-sensitive hydrogel. Author(s): Chang KH, Chung IS, Park CH. Source: Biotechnology Letters. 2003 February; 25(4): 335-8. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12882548&dopt=Abstract

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Crohn's mucosa harbors adherent-invasive E. coli. Author(s): Boedeker EC. Source: Inflammatory Bowel Diseases. 2000 May; 6(2): 155. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10833079&dopt=Abstract

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Crowd control: quorum sensing in pathogenic E. coli. Author(s): Gruenheid S, Finlay BB. Source: Trends in Microbiology. 2000 October; 8(10): 442-3. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11044672&dopt=Abstract

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Crystal structure at 2.4 A resolution of E. coli serine hydroxymethyltransferase in complex with glycine substrate and 5-formyl tetrahydrofolate. Author(s): Scarsdale JN, Radaev S, Kazanina G, Schirch V, Wright HT. Source: Journal of Molecular Biology. 2000 February 11; 296(1): 155-68. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10656824&dopt=Abstract

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Crystal structures of E. coli nicotinate mononucleotide adenylyltransferase and its complex with deamido-NAD. Author(s): Zhang H, Zhou T, Kurnasov O, Cheek S, Grishin NV, Osterman A. Source: Structure (Cambridge, Mass. : 2001). 2002 January; 10(1): 69-79. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11796112&dopt=Abstract

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Cytokine release of whole blood from adult female donors challenged with mistletoe lectin-1 standardised mistletoe extract and E. coli endotoxin or phytohaemagglutinin (PHA). Author(s): Braun JM, Blackwell CC, Weir DM, Beuth J. Source: Anticancer Res. 2003 March-April; 23(2B): 1349-52. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12820393&dopt=Abstract

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De novo development of presumed cavernomas following resolution of E. coli subdural empyemas. Author(s): Fender LJ, Lenthall RK, Jaspan T. Source: Neuroradiology. 2000 October; 42(10): 778-80. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11110086&dopt=Abstract

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Death came in the water. E. coli breaks out at a N.Y. county fair. Author(s): Spake A. Source: U.S. News & World Report. 1999 September 20; 127(11): 56. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10621508&dopt=Abstract

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Detection and characterization of Shiga toxigenic Escherichia coli by using multiplex PCR assays for stx1, stx2, eaeA, enterohemorrhagic E. coli hlyA, rfbO111, and rfbO157. Author(s): Paton AW, Paton JC. Source: Journal of Clinical Microbiology. 1998 February; 36(2): 598-602. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=9466788&dopt=Abstract

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Detection of circulating CEA molecules in human sera and leukopheresis of peripheral blood stem cells with E. coli expressed bispecific CEAScFv-streptavidin fusion protein-based immuno-PCR technique. Author(s): Ren J, Ge L, Li Y, Bai J, Liu WC, Si XM. Source: Annals of the New York Academy of Sciences. 2001 September; 945: 116-8. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11708464&dopt=Abstract

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Detection of Escherichia coli O157:H7 and other verocytotoxin-producing E. coli (VTEC) in food. Author(s): Vernozy-Rozand C. Source: Journal of Applied Microbiology. 1997 May; 82(5): 537-51. Review. Erratum In: J Appl Microbiol 1998 September; 85(3): 634. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=9172396&dopt=Abstract

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Detection of eukaryotic cDNA in differential display is enhanced by the addition of E. coli RNA. Author(s): Melichar H, Bosch I, Molnar GM, Huang L, Pardee AB. Source: Biotechniques. 2000 January; 28(1): 76-82. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10649774&dopt=Abstract

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Diarrheagenic Escherichia coli isolated from stools of sporadic cases of diarrheal illness in Osaka City, Japan between 1997 and 2000: prevalence of enteroaggregative E. coli heat-stable enterotoxin 1 gene-possessing E. coli. Author(s): Nishikawa Y, Zhou Z, Hase A, Ogasawara J, Kitase T, Abe N, Nakamura H, Wada T, Ishii E, Haruki K; Surveillance Team. Source: Japanese Journal of Infectious Diseases. 2002 December; 55(6): 183-90. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12606826&dopt=Abstract

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Dihydropyrimidine dehydrogenase deficiency. Identification of two novel mutations and expression of missense mutations in E. coli. Author(s): Vreken P, van Kuilenburg AB, Meinsma R, van Gennip AH. Source: Advances in Experimental Medicine and Biology. 1998; 431: 341-6. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=9598088&dopt=Abstract

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Dihydropyrimidine dehydrogenase deficiency: a novel mutation and expression of missense mutations in E. coli. Author(s): Vreken P, van Kuilenburg AB, Meinsma R, Beemer FA, Duran M, van Gennip AH. Source: Journal of Inherited Metabolic Disease. 1998 June; 21(3): 276-9. Erratum In: J Inherit Metab Dis 1998 August; 21(6): 623. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=9686374&dopt=Abstract

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Display of an inhibin epitope in a surface-exposed loop of the E. coli heat-labile enterotoxin B subunit. Author(s): Sewani CR, Bagdasarian MM, Ireland JJ, Bagdasarian M. Source: Vaccine. 1998 October; 16(17): 1611-9. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=9713936&dopt=Abstract

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Dissecting the interaction network of multiprotein complexes by pairwise coexpression of subunits in E. coli. Author(s): Fribourg S, Romier C, Werten S, Gangloff YG, Poterszman A, Moras D. Source: Journal of Molecular Biology. 2001 February 16; 306(2): 363-73. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11237605&dopt=Abstract

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Distribution of aggA and aafA gene sequences among Escherichia coli isolates with genotypic or phenotypic characteristics, or both, of enteroaggregative E. coli. Author(s): Elias WP, Suzart S, Trabulsi LR, Nataro JP, Gomes TA. Source: Journal of Medical Microbiology. 1999 June; 48(6): 597-9. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10359310&dopt=Abstract

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Distribution of the secondary type III secretion system locus found in enterohemorrhagic Escherichia coli O157:H7 isolates among Shiga toxin-producing E. coli strains. Author(s): Makino S, Tobe T, Asakura H, Watarai M, Ikeda T, Takeshi K, Sasakawa C. Source: Journal of Clinical Microbiology. 2003 June; 41(6): 2341-7. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12791847&dopt=Abstract

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DNA mismatch repair and acquired cisplatin resistance in E. coli and human ovarian carcinoma cells. Author(s): Massey A, Offman J, Macpherson P, Karran P. Source: Dna Repair. 2003 January 2; 2(1): 73-89. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12509269&dopt=Abstract

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Does experimental evolution reflect patterns in natural populations? E. coli strains from long-term studies compared with wild isolates. Author(s): Souza V, Travisano M, Turner PE, Eguiarte LE. Source: Antonie Van Leeuwenhoek. 2002 August; 81(1-4): 143-53. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12448713&dopt=Abstract

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Double-blind randomised placebo-controlled phase III study of an E. coli extract plus 5-fluorouracil versus 5-fluorouracil in patients with advanced colorectal cancer. Author(s): Unger C, Haring B, Kruse A, Thumann A, Schneider B, Clemm C, Weber B, Clevert HD, Hockertz S, Kalousek MB. Source: Arzneimittel-Forschung. 2001; 51(4): 332-8. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11367875&dopt=Abstract

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Drug sensitivity pattern of E. coli causing urinary tract infection in diabetic and nondiabetic patients. Author(s): Jinnah F, Islam MS, Rumi MA, Morshed MG, Huq F. Source: J Int Med Res. 1996 May-June; 24(3): 296-301. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=8725992&dopt=Abstract

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Drug toxicity in E. coli cells expressing human topoisomerase I. Author(s): Taylor ST, Menzel R. Source: Methods in Molecular Biology (Clifton, N.J.). 2001; 95: 195-204. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11089232&dopt=Abstract

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Dual-expression vectors for efficient protein expression in both E. coli and mammalian cells. Author(s): Mullinax RL, Wong DT, Davis HA, Padgett KA, Sorge JA. Source: Methods in Molecular Biology (Clifton, N.J.). 2003; 205: 19-30. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12491877&dopt=Abstract

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Dysentery associated with invasive E. coli 028ac in an adult: a case report. Author(s): Mutanda LN. Source: East Afr Med J. 1987 June; 64(6): 418-23. No Abstract Available. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=3319510&dopt=Abstract

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E. coli cellulitis. Author(s): Gach JE, Charles-Holmes R, Ghose A. Source: Clinical and Experimental Dermatology. 2002 September; 27(6): 523-5. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12372100&dopt=Abstract

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E. coli dihydroorotate dehydrogenase reveals structural and functional distinctions between different classes of dihydroorotate dehydrogenases. Author(s): Norager S, Jensen KF, Bjornberg O, Larsen S. Source: Structure (Cambridge, Mass. : 2001). 2002 September; 10(9): 1211-23. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12220493&dopt=Abstract

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E. coli exposed! Author(s): Holton WC. Source: Environmental Health Perspectives. 2002 October; 110(10): A586-9. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12361939&dopt=Abstract

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E. coli expression of TIMP-4 and comparative kinetic studies with TIMP-1 and TIMP2: insights into the interactions of TIMPs and matrix metalloproteinase 2 (gelatinase A). Author(s): Troeberg L, Tanaka M, Wait R, Shi YE, Brew K, Nagase H. Source: Biochemistry. 2002 December 17; 41(50): 15025-35. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12475252&dopt=Abstract

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E. coli heat-stable enterotoxin and guanylyl cyclase C: new functions and unsuspected actions. Author(s): Giannella RA, Mann EA. Source: Trans Am Clin Climatol Assoc. 2003; 114: 67-85; Discussion 85-6. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12813912&dopt=Abstract

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E. coli O157 phage type 21/28 outbreak in North Cumbria associated with pasteurized milk. Author(s): Goh S, Newman C, Knowles M, Bolton FJ, Hollyoak V, Richards S, Daley P, Counter D, Smith HR, Keppie N. Source: Epidemiology and Infection. 2002 December; 129(3): 451-7. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12558327&dopt=Abstract

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E. coli outbreak deaths spark judicial inquiry in Canada. Author(s): Kondro W. Source: Lancet. 2000 June 10; 355(9220): 2058. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10885367&dopt=Abstract

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E. coli selection of human genes encoding secreted and membrane proteins based on cDNA fusions to a leaderless beta-lactamase reporter. Author(s): Tan R, Jiang X, Jackson A, Jin P, Yang J, Lee E, Duggan B, Stuve LL, Fu GK. Source: Genome Research. 2003 August; 13(8): 1938-43. Epub 2003 July 17. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12869575&dopt=Abstract

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E. coli, antibiotics and hemolytic-uremic syndrome in children. Author(s): Farquhar D. Source: Cmaj : Canadian Medical Association Journal = Journal De L'association Medicale Canadienne. 2000 August 22; 163(4): 438. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10976267&dopt=Abstract

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E. coli, antibiotics, and the hemolytic-uremic syndrome. Author(s): Zimmerhackl LB. Source: The New England Journal of Medicine. 2000 June 29; 342(26): 1990-1. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10874069&dopt=Abstract

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Effect of fragment Asp1961-Glu1978 in fibronectin on the expression of triple-domain polypeptide in E. coli. Author(s): Li D, Feng Z, Zhang G, Zhang H, Fan Q. Source: J Tongji Med Univ. 1998; 18(3): 129-33. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10806808&dopt=Abstract

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Effect of the adhesive antibiotic TA on adhesion and initial growth of E. coli on silicone rubber. Author(s): Simhi E, van der Mei HC, Ron EZ, Rosenberg E, Busscher HJ. Source: Fems Microbiology Letters. 2000 November 1; 192(1): 97-100. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11040435&dopt=Abstract

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Effects of recombinant human growth hormone on rat septic shock with intraabdominal infection by E. coli. Author(s): Huang Y, Wang SR, Yi C, Ying MY, Lin Y, Zhi MH. Source: World Journal of Gastroenterology : Wjg. 2002 December; 8(6): 1134-7. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12439940&dopt=Abstract

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Expression and characterization of E. coli-produced soluble, functional human dihydroorotate dehydrogenase: a potential target for immunosuppression. Author(s): Neidhardt EA, Punreddy SR, McLean JE, Hedstrom L, Grossman TH. Source: J Mol Microbiol Biotechnol. 1999 August; 1(1): 183-8. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10941801&dopt=Abstract

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Expression and characterization of recombinant human cytochrome c in E. coli. Author(s): Jeng WY, Chen CY, Chang HC, Chuang WJ. Source: Journal of Bioenergetics and Biomembranes. 2002 December; 34(6): 423-31. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12678434&dopt=Abstract

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Expression of chemokines in the periplasmic space of E. coli. Author(s): Pfirstinger J, Mack M. Source: Methods in Molecular Biology (Clifton, N.J.). 2000; 138: 41-5. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10840741&dopt=Abstract

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Expression of enzymatically-active phospholipase Cgamma2 in E. coli. Author(s): Ozdener F, Kunapuli SP, Daniel JL. Source: J Biochem Mol Biol. 2002 September 30; 35(5): 508-12. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12359094&dopt=Abstract

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Expression of immunoreactive forms of the hepatitis C NS5A protein in E. coli and their use for diagnostic assays. Author(s): Kalamvoki M, Miriagou V, Hadziyannis A, Georgopoulou U, Varaklioti A, Hadziyannis S, Mavromara P. Source: Archives of Virology. 2002 September; 147(9): 1733-45. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12209313&dopt=Abstract

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Expression of neurotrophic factors such as GDNF in the E. coli system. Author(s): Huang BR, Ma XM. Source: Methods in Molecular Biology (Clifton, N.J.). 2001; 169: 101-14. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11142006&dopt=Abstract

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Expression of stable hepatitis B viral polymerase associated with GRP94 in E. coli. Author(s): Kim SS, Shin HJ, Cho YH, Rho HM. Source: Archives of Virology. 2000; 145(7): 1305-20. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10963339&dopt=Abstract

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Factors affecting neonatal E. coli K1 rectal colonization. Author(s): Peter G, Nelson JS. Source: The Journal of Pediatrics. 1978 November; 93(5): 866-9. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=361941&dopt=Abstract

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Fatalities from E. coli O157. Author(s): O'Flanagan D. Source: Ir Med J. 1997 April-May; 90(3): 88, 90. No Abstract Available. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=9183083&dopt=Abstract

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Fecal colonization with P-fimbriated Escherichia coli in newborn children and relation to development of extraintestinal E. coli infections. Author(s): Tullus K. Source: Acta Paediatr Scand Suppl. 1987; 334: 1-35. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=2889317&dopt=Abstract

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Finding of “E. coli” phage in urinary tract infections. Author(s): Caroli G, Armani G, Levre E, Jefferson TO. Source: Ann Sclavo. 1980 September-October; 22(5): 857-60. No Abstract Available. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=7271343&dopt=Abstract

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Fluorescent anti-colonic and E. coli antibodies in ulcerative colitis. Author(s): Marcussen H. Source: Scandinavian Journal of Gastroenterology. 1978; 13(3): 277-81. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=113868&dopt=Abstract

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Fluorescent-actin staining (FAS) test: a novel assay to detect enteropathogenic E. coli. Author(s): Shariff M, Bhandari N, Saini S. Source: Indian J Pediatr. 1994 November-December; 61(6): 737-8. No Abstract Available. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=7721384&dopt=Abstract

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Folding and characterization of the amino-terminal domain of human tissue inhibitor of metalloproteinases-1 (TIMP-1) expressed at high yield in E. coli. Author(s): Huang W, Suzuki K, Nagase H, Arumugam S, Van Doren SR, Brew K. Source: Febs Letters. 1996 April 15; 384(2): 155-61. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=8612814&dopt=Abstract

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Foodborne diseases: Shiga toxin producing E. coli (STEC). Author(s): Bower JR. Source: The Pediatric Infectious Disease Journal. 1999 October; 18(10): 909-10. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10530589&dopt=Abstract

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Formation of inclusion bodies may be the key factor for the stability of expressed products in E. coli. Author(s): Wei G, Tang JG. Source: Biochem Mol Biol Int. 1995 November; 37(5): 895-901. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=8624495&dopt=Abstract

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Frequency of E. coli K antigens in urinary-tract infections in children. Author(s): Kaijser B, Hanson LA, Jodal U, Lidin-Janson G, Robbins JB. Source: Lancet. 1977 March 26; 1(8013): 663-6. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=66470&dopt=Abstract

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Fresh human colostrum for the prevention of E. coli diarrhea--a clinical experience. Author(s): Larguia AM, Urman J, Stoliar OA, Ceriani JM, O'Donnell A, Buscaglia JC, Martinez JC. Source: J Trop Pediatr Environ Child Health. 1977 December; 23(6): 289-90. No Abstract Available. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=342720&dopt=Abstract

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Further studies on the detection of mutagenic and genotoxic activity in human faeces: aerobic and anaerobic fluctuation tests with S. typhimurium and E. coli, and the SOS Chromotest. Author(s): Venitt S, Bosworth D. Source: Mutagenesis. 1986 January; 1(1): 49-64. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=3325736&dopt=Abstract

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Fusion expression of human pro-urokinase with E. coli thioredoxin. Author(s): Sun AL, Hua ZC, Yao J, Yang YH, Yin DQ. Source: Biochem Mol Biol Int. 1998 October; 46(3): 479-86. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=9818087&dopt=Abstract

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Fusion proteins with heterologous T helper epitopes. Recombinant E. coli heat-stable enterotoxin proteins. Author(s): Lowenadler B, Lycke N. Source: International Reviews of Immunology. 1994; 11(2): 103-11. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=7519227&dopt=Abstract

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Gal-Gal pili vaccines prevent pyelonephritis by piliated Escherichia coli in a murine model. Single-component Gal-Gal pili vaccines prevent pyelonephritis by homologous and heterologous piliated E. coli strains. Author(s): Pecha B, Low D, O'Hanley P. Source: The Journal of Clinical Investigation. 1989 June; 83(6): 2102-8. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=2566625&dopt=Abstract

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Gene synthesis and expression in E. coli for pump, a human matrix metalloproteinase. Author(s): Ye QZ, Johnson LL, Baragi V. Source: Biochemical and Biophysical Research Communications. 1992 July 15; 186(1): 143-9. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=1632763&dopt=Abstract

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Genes of pyelonephritogenic E. coli required for digalactoside-specific agglutination of human cells. Author(s): Lindberg FP, Lund B, Normark S. Source: The Embo Journal. 1984 May; 3(5): 1167-73. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=6145590&dopt=Abstract

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Genetic characterization of the uropathogenic E. coli strain 536--a subtractive hybridization analysis. Author(s): Janke B, Hacker J, Blum-Oehler G. Source: Advances in Experimental Medicine and Biology. 2000; 485: 53-6. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11109086&dopt=Abstract

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Genetic diversity and temporal variation in the E. coli population of a human host. Author(s): Caugant DA, Levin BR, Selander RK. Source: Genetics. 1981 July; 98(3): 467-90. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=7037535&dopt=Abstract

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Genome sequence of E. coli O157:H7. Author(s): Sperandio V. Source: Trends in Microbiology. 2001 April; 9(4): 159. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11286870&dopt=Abstract

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Germs, arteries or both? Differentiating E. coli O157 from ischemic colitis. Author(s): Cobden I. Source: The American Journal of Gastroenterology. 1998 July; 93(7): 1022-4. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=9672323&dopt=Abstract

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Growth of Escherichia coli O157 in poorly fermented laboratory silage: a possible environmental dimension in the epidemiology of E. coli O157. Author(s): Fenlon DR, Wilson J. Source: Letters in Applied Microbiology. 2000 February; 30(2): 118-21. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10736012&dopt=Abstract

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Guinea pig apolipoprotein C-II: expression in E. coli, functional studies of recombinant wild-type and mutated variants, and distribution on plasma lipoproteins. Author(s): Andersson Y, Lookene A, Shen Y, Nilsson S, Thelander L, Olivecrona G. Source: Journal of Lipid Research. 1997 October; 38(10): 2111-24. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=9374133&dopt=Abstract

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Gut feelings: enteropathogenic E. coli (EPEC) interactions with the host. Author(s): Goosney DL, Gruenheid S, Finlay BB. Source: Annual Review of Cell and Developmental Biology. 2000; 16: 173-89. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11031234&dopt=Abstract

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Hemolytic uremic syndrome surveillance to monitor trends in infection with Escherichia coli O157:H7 and other shiga toxin-producing E. coli. Author(s): Mahon BE, Griffin PM, Mead PS, Tauxe RV. Source: Emerging Infectious Diseases. 1997 July-September; 3(3): 409-12. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=9284395&dopt=Abstract

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Hemolytic-uremic syndrome surveillance to monitor trends in infection with Escherichia coli O157 and non-O157 enterohemorrhagic E. coli in Austria. Author(s): Fischer H, Konig P, Dierich MP, Allerberger F. Source: The Pediatric Infectious Disease Journal. 2001 March; 20(3): 316-8. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11303839&dopt=Abstract

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High cytoplasmic expression in E. coli, purification, and in vitro refolding of a single chain Fv antibody fragment against the hepatitis B surface antigen. Author(s): Sanchez L, Ayala M, Freyre F, Pedroso I, Bell H, Falcon V, Gavilondo JV. Source: Journal of Biotechnology. 1999 June 11; 72(1-2): 13-20. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10406095&dopt=Abstract

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High expression of human amelogenin in E. coli. Author(s): Deutsch D, Chityat E, Hekmati M, Palmon A, Farkash Y, Dafni L. Source: Advances in Dental Research. 1996 November; 10(2): 187-93; Discussion 194. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=9206336&dopt=Abstract

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High expression of synthetic human interferon-gamma cDNA in E. coli. Author(s): Wang Z, Yang D, Wang Q, Li B, Lu Z, Yu J, Zheng H, Fan P, Tang J, Qian M, et al. Source: Science in China. Series B, Chemistry, Life Sciences & Earth Sciences. 1995 September; 38(9): 1084-93. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=8554677&dopt=Abstract

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High level expression in E. coli of an alternate reading frame of pS2 mRNA that encodes a mimotope of human breast epithelial mucin tandem repeat. Author(s): Larocca D, Peterson JA, Ceriani RL. Source: Hybridoma. 1992 April; 11(2): 191-201. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=1376717&dopt=Abstract

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High-level expression of active human plasminogen activator inhibitor type 1 (PAI-1) in E. coli. Author(s): Zhou A, Pei Y, Wu H, Dong X, Xu X. Source: Biochem Mol Biol Int. 1996 May; 39(2): 235-42. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=8799449&dopt=Abstract

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High-level expression of cecropin CMIV in E. coli from a fusion construct containing the human tumor necrosis factor. Author(s): Wang L, Wu H, Dou F, Xie W, Xu X. Source: Biochem Mol Biol Int. 1997 April; 41(5): 1051-6. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=9137837&dopt=Abstract

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High-level expression of fully active human glutaredoxin (thioltransferase) in E. coli and characterization of Cys7 to Ser mutant protein. Author(s): Padilla CA, Spyrou G, Holmgren A. Source: Febs Letters. 1996 January 2; 378(1): 69-73. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=8549805&dopt=Abstract

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High-level expression of human histone H4 in E. coli. Author(s): Burnett VL, Springer DL. Source: Biotechniques. 1999 January; 26(1): 30-2, 34. No Abstract Available. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=9894588&dopt=Abstract

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Homology in accessory proteins of replicative polymerases--E. coli to humans. Author(s): O'Donnell M, Onrust R, Dean FB, Chen M, Hurwitz J. Source: Nucleic Acids Research. 1993 January 11; 21(1): 1-3. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=8441605&dopt=Abstract

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HPI of high-virulent Yersinia is found in E. coli strains causing urinary tract infection. Structural, functional aspects, and distribution. Author(s): Schubert S, Sorsa JL, Cuenca S, Fischer D, Jacobi CA, Heesemann J. Source: Advances in Experimental Medicine and Biology. 2000; 485: 69-73. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11109089&dopt=Abstract

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Human cathepsin E produced in E. coli. Author(s): Hill J, Montgomery DS, Kay J. Source: Febs Letters. 1993 July 12; 326(1-3): 101-4. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=8325357&dopt=Abstract

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Human coproporphyrinogen oxidase. Biochemical characterization of recombinant normal and R231W mutated enzymes expressed in E. coli as soluble, catalytically active homodimers. Author(s): Martasek P, Camadro JM, Raman CS, Lecomte MC, Le Caer JP, Demeler B, Grandchamp B, Labbe P. Source: Cell Mol Biol (Noisy-Le-Grand). 1997 February; 43(1): 47-58. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=9074788&dopt=Abstract

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Human interleukin-1 receptor antagonist. High yield expression in E. coli and examination of cysteine residues. Author(s): Steinkasserer A, Solari R, Mott HR, Aplin RT, Robinson CC, Willis AC, Sim RB. Source: Febs Letters. 1992 September 21; 310(1): 63-5. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=1388125&dopt=Abstract

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Human milk fractions inhibit the adherence of diffusely adherent Escherichia coli (DAEC) and enteroaggregative E. coli (EAEC) to HeLa cells. Author(s): Nascimento de Araujo A, Giugliano LG. Source: Fems Microbiology Letters. 2000 March 1; 184(1): 91-4. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10689172&dopt=Abstract

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Human tyrosine tRNA is also internally cleavable by E. coli ribonuclease P RNA ribozyme in vitro. Author(s): Ando T, Tanaka T, Hori Y, Sakai E, Kikuchi Y. Source: Bioscience, Biotechnology, and Biochemistry. 2001 December; 65(12): 2798-801. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11826982&dopt=Abstract

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Human uracil-DNA glycosylase complements E. coli ung mutants. Author(s): Olsen LC, Aasland R, Krokan HE, Helland DE. Source: Nucleic Acids Research. 1991 August 25; 19(16): 4473-8. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=1886771&dopt=Abstract

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Hybridization of strains of Escherichia coli O157 with probes derived from the eaeA gene of enteropathogenic E. coli and the eaeA homolog from a Vero cytotoxinproducing strain of E. coli O157. Author(s): Willshaw GA, Scotland SM, Smith HR, Cheasty T, Thomas A, Rowe B. Source: Journal of Clinical Microbiology. 1994 April; 32(4): 897-902. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=8027340&dopt=Abstract

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Hypersensitivity reactions to Escherichia coli-derived polyethylene glycolatedasparaginase associated with subsequent immediate skin test reactivity to E. coliderived granulocyte colony-stimulating factor. Author(s): Stone HD Jr, DiPiro C, Davis PC, Meyer CF, Wray BB. Source: The Journal of Allergy and Clinical Immunology. 1998 March; 101(3): 429-31. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=9525466&dopt=Abstract

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Identification of a new Escherichia coli She haemolysin homolog in avian E. coli. Author(s): Reingold J, Starr N, Maurer J, Lee MD. Source: Veterinary Microbiology. 1999 April 1; 66(2): 125-34. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10227474&dopt=Abstract

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Identification of epitope recognized by an anti-c-myc monoclonal antibody that crossreacts with E. coli sigma factor using phage display libraries. Author(s): Ikegaki N, Tang XX, Kay BK, Kennett RH. Source: Immunotechnology : an International Journal of Immunological Engineering. 1996 February; 2(1): 37-46. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=9373326&dopt=Abstract

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Identification of further proteolytic cleavage sites in the Southampton calicivirus polyprotein by expression of the viral protease in E. coli. Author(s): Liu BL, Viljoen GJ, Clarke IN, Lambden PR. Source: The Journal of General Virology. 1999 February; 80 ( Pt 2): 291-6. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10073687&dopt=Abstract

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Identification of non-telomeric G4-DNA binding proteins in human, E. coli, yeast, and Arabidopsis. Author(s): Kang SG, Henderson E. Source: Molecules and Cells. 2002 December 31; 14(3): 404-10. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12521304&dopt=Abstract

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Identification of urovirulence traits in Escherichia coli by comparison of urinary and rectal E. coli isolates from dogs with urinary tract infection. Author(s): Johnson JR, Kaster N, Kuskowski MA, Ling GV. Source: Journal of Clinical Microbiology. 2003 January; 41(1): 337-45. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12517870&dopt=Abstract

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Illness outbreak associated with Escherichia coli O157:H7 in Genoa salami. E. coli O157:H7 Working Group. Author(s): Williams RC, Isaacs S, Decou ML, Richardson EA, Buffett MC, Slinger RW, Brodsky MH, Ciebin BW, Ellis A, Hockin J. Source: Cmaj : Canadian Medical Association Journal = Journal De L'association Medicale Canadienne. 2000 May 16; 162(10): 1409-13. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10834043&dopt=Abstract

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Immunological cross reactivity of eaeA (intimin) from E. coli that cause attaching and effacing lesions in humans and rabbits. Author(s): Agin TS, Wolf MK. Source: Advances in Experimental Medicine and Biology. 1997; 412: 103-4. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=9192001&dopt=Abstract

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In vivo gene therapy of cancer with E. coli purine nucleoside phosphorylase. Author(s): Parker WB, King SA, Allan PW, Bennett LL Jr, Secrist JA 3rd, Montgomery JA, Gilbert KS, Waud WR, Wells AH, Gillespie GY, Sorscher EJ. Source: Human Gene Therapy. 1997 September 20; 8(14): 1637-44. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=9322865&dopt=Abstract

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In vivo sensitization of ovarian tumors to chemotherapy by expression of E. coli purine nucleoside phosphorylase in a small fraction of cells. Author(s): Gadi VK, Alexander SD, Kudlow JE, Allan P, Parker WB, Sorscher EJ. Source: Gene Therapy. 2000 October; 7(20): 1738-43. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11083495&dopt=Abstract

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Incidence of E. coli O157:H7 and other enteropathogens in a Spanish hospital. Author(s): Lopez AG, Zazo JL, Diaz RD, de Guevara C. Source: European Journal of Epidemiology. 2000 March; 16(3): 303-4. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10870948&dopt=Abstract

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Inhibition of B16-BL6 melanoma lung colonies by semisynthetic sulfaminoheparosan sulfates from E. coli K5 polysaccharide. Author(s): Poggi A, Rossi C, Casella N, Bruno C, Sturiale L, Dossi C, Naggi A. Source: Seminars in Thrombosis and Hemostasis. 2002 August; 28(4): 383-92. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12244486&dopt=Abstract

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Inhibition of phagocytosis of E. coli by B. fragilis group--an in vitro study. Author(s): Beena VK, Kumari N, Shivananda PG. Source: Indian J Pathol Microbiol. 1997 July; 40(3): 373-6. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=9354011&dopt=Abstract

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Inhibitory effect of probiotic Escherichia coli strain Nissle 1917 on adhesion to and invasion of intestinal epithelial cells by adherent-invasive E. coli strains isolated from patients with Crohn's disease. Author(s): Boudeau J, Glasser AL, Julien S, Colombel JF, Darfeuille-Michaud A. Source: Alimentary Pharmacology & Therapeutics. 2003 July 1; 18(1): 45-56. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12848625&dopt=Abstract

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Interaction of lipopolysaccharide with a mammalian lyso-phosphatidate acyltransferase (LPAAT) transfected into E. coli, and effect of lisofylline on LPAAT transfected into mammalian cells. Author(s): Bursten SL. Source: Prog Clin Biol Res. 1998; 397: 345-56. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=9575575&dopt=Abstract

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Interleukin-10 produced by the innate immune system masks in vitro evidence of acquired T-cell immunity to E. coli. Author(s): Hessle C, Hanson LA, Wold AE. Source: Scandinavian Journal of Immunology. 2000 July; 52(1): 13-20. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10886779&dopt=Abstract

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Interrelationship between virulence properties of uropathogenic E. coli and blood group phenotype of patients with chronic urinary tract infection. Author(s): Funfstuck R, Jacobsohn N, Stein G. Source: Advances in Experimental Medicine and Biology. 2000; 485: 201-12. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11109107&dopt=Abstract

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Investigation of an E. coli O157:H7 outbreak in Brooks, Alberta, June-July 2002: the role of occult cases in the spread of infection within a daycare setting. Author(s): Galanis E, Longmore K, Hasselback P, Swann D, Ellis A, Panaro L. Source: Can Commun Dis Rep. 2003 February 1; 29(3): 21-8. English, French. No Abstract Available. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12629877&dopt=Abstract

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Investigation of an outbreak of E. coli O157 infections associated with a trip to France of schoolchildren from Somerset, England. Author(s): Duffell E, Espie E, Nichols T, Adak GK, De Valk H, Anderson K, Stuart JM. Source: Euro Surveillance : Bulletin Europeen Sur Les Maladies Transmissibles = European Communicable Disease Bulletin. 2003 April; 8(4): 81-6. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12764237&dopt=Abstract

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Involvement of the Cpx signal transduction pathway of E. coli in biofilm formation. Author(s): Dorel C, Vidal O, Prigent-Combaret C, Vallet I, Lejeune P. Source: Fems Microbiology Letters. 1999 September 1; 178(1): 169-75. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10483736&dopt=Abstract

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Isolation of Shiga toxin-producing Escherichia coli O103 from sheep using automated immunomagnetic separation (AIMS) and AIMS-ELISA: sheep as the source of a clinical E. coli O103 case? Author(s): Urdahl AM, Cudjoe K, Wahl E, Heir E, Wasteson Y. Source: Letters in Applied Microbiology. 2002; 35(3): 218-22. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12180944&dopt=Abstract

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Japan shuns radishes after 'possible link' to E. coli. Author(s): Swinbanks D. Source: Nature. 1996 August 15; 382(6592): 567. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=8757116&dopt=Abstract

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Juice maker fined record amount for E. coli-tainted product. Author(s): Henkel J. Source: Fda Consumer. 1999 January-February; 33(1): 34-5. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10030145&dopt=Abstract

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K99 surface haemagglutinin of enterotoxigenic E. coli recognize terminal Nacetylgalactosamine and sialic acid residues of glycophorin and other complex glycoconjugates. Author(s): Lindahl M, Wadstrom T. Source: Veterinary Microbiology. 1984 July; 9(3): 249-57. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=6147916&dopt=Abstract

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Killer bacteria/E. coli O157:H7. Anatomy of an outbreak. Author(s): Kluger P. Source: Time. 1998 August 3; 152(5): 56-62. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10181916&dopt=Abstract

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KIN, a mammalian nuclear protein immunologically related to E. coli RecA protein. Author(s): Angulo JF, Moreau PL, Maunoury R, Laporte J, Hill AM, Bertolotti R, Devoret R. Source: Mutation Research. 1989 March; 217(2): 123-34. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=2493134&dopt=Abstract

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Kinetic study of human beta-1,4-galactosyltransferase expressed in E. coli. Author(s): Nakazawa K, Furukawa K, Narimatsu H, Kobata A. Source: Journal of Biochemistry. 1993 June; 113(6): 747-53. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=8370673&dopt=Abstract

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Laboratory investigation of an E. coli O157:H7 outbreak associated with swimming in Battle Ground Lake, Vancouver, Washington. Author(s): Samadpour M, Stewart J, Steingart K, Addy C, Louderback J, McGinn M, Ellington J, Newman T. Source: Journal of Environmental Health. 2002 June; 64(10): 16-20, 26, 25. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12049000&dopt=Abstract

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Large scale, in situ isolation of periplasmic IGF-I from E. coli. Author(s): Hart RA, Lester PM, Reifsnyder DH, Ogez JR, Builder SE. Source: Biotechnology (N Y). 1994 November; 12(11): 1113-7. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=7765554&dopt=Abstract

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Large-scale isolation and purification of proteins from recombinant E. coli. Author(s): McGregor WC. Source: Annals of the New York Academy of Sciences. 1983; 413: 231-7. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=6367588&dopt=Abstract

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L-asparagine depletion and L-asparaginase activity in children with acute lymphoblastic leukemia receiving i.m. or i.v. Erwinia C. or E. coli L-asparaginase as first exposure. Author(s): Rizzari C, Zucchetti M, Conter V, Diomede L, Bruno A, Gavazzi L, Paganini M, Sparano P, Lo Nigro L, Arico M, Milani M, D'Incalci M. Source: Annals of Oncology : Official Journal of the European Society for Medical Oncology / Esmo. 2000 February; 11(2): 189-93. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10761754&dopt=Abstract

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Letter: Enteropathogenic E. coli O 124 in the United Kingdom. Author(s): Rowe B, Gross RJ, Allen HA. Source: Lancet. 1974 February 9; 1(7850): 224-5. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=4129919&dopt=Abstract

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Letter: Enteropathogenic E. coli. Author(s): Smith HW. Source: Lancet. 1976 June 19; 1(7973): 1348-9. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=58332&dopt=Abstract

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Letter: Public health hazard of antibiotic resistance in enterobacterial (E. coli and Salmonella) isolates from poultry in Ghana. Author(s): Corkish JD, Assoku RK. Source: Ghana Med J. 1973 December; 12(4): 430-2. No Abstract Available. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=4618961&dopt=Abstract

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Letter: Rheovirus and E. coli in infantile enteritis. Author(s): Rowe B, Gross RJ, Scotland SM. Source: Journal of Clinical Pathology. 1976 August; 29(8): 761-2. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=182725&dopt=Abstract

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Letter: Serotyping of E. coli. Author(s): Sack RB. Source: Lancet. 1976 May 22; 1(7969): 1132. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=57542&dopt=Abstract

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Letter: Serotyping of E. coli. Author(s): Rowe B, Gross RJ, Scotland SM. Source: Lancet. 1976 July 3; 2(7975): 37-8. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=59090&dopt=Abstract

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Ligand binding analysis of human neuropeptide Y1 receptor mutants expressed in E. coli. Author(s): Munch G, Walker P, Shine J, Herzog H. Source: Receptors & Channels. 1995; 3(4): 291-7. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=8834002&dopt=Abstract

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Ligand binding properties of human cellular retinoic acid binding protein II expressed in E. coli as a glutathione-S-transferase fusion protein. Author(s): Redfern CP, Wilson KE. Source: Febs Letters. 1993 April 26; 321(2-3): 163-8. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=8386677&dopt=Abstract

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Live E. coli cells to treat uremia. Author(s): Wrong O. Source: Nature Medicine. 1997 January; 3(1): 3; Author Reply 3-4. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=8986726&dopt=Abstract

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Liver cirrhosis with synchronous gas gangrene and spontaneous bacterial peritonitis due to E. coli. Author(s): Murata K, Shimizu A, Takase K, Nakano T, Tameda Y. Source: Journal of Gastroenterology. 1997 April; 32(2): 264-7. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=9085180&dopt=Abstract

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Local and systemic antibody response in infants after oral administration of inactivated enteropathogenic E. coli serotype O111 and O55. Author(s): Lodinova-Zadnikova R, Korych B, Gajdostikova K. Source: Folia Microbiol (Praha). 1990; 35(2): 155-62. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=1696237&dopt=Abstract

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Localization of the cellular-fibronectin-specific epitope recognized by the monoclonal antibody IST-9 using fusion proteins expressed in E. coli. Author(s): Carnemolla B, Borsi L, Zardi L, Owens RJ, Baralle FE. Source: Febs Letters. 1987 May 11; 215(2): 269-73. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=2438158&dopt=Abstract

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Localization of the xanthine guanine phosphoribosyl transferase gene (gpt) of E. coli in AS52 metaphase cells by fluorescence in situ hybridization. Author(s): Michaelis KC, Helvering LM, Kindig DE, Garriott ML, Richardson KK. Source: Environmental and Molecular Mutagenesis. 1994; 24(3): 176-80. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=7957121&dopt=Abstract

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Localized production of human E-cadherin-derived first repeat in Escherichia coli. Author(s): Makagiansar IT, Ikesue A, Nguyen PD, Urbauer JL, Urbauer RJ, Siahaan TJ. Source: Protein Expression and Purification. 2002 December; 26(3): 449-54. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12460769&dopt=Abstract

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Mammalian expression vectors for epitope tag fusion proteins that are toxic in E. coli. Author(s): Jakobi R, McCarthy CC, Koeppel MA. Source: Biotechniques. 2002 December; 33(6): 1218-20, 1222. No Abstract Available. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12503302&dopt=Abstract

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Mammalian homologue of E. coli Ras-like GTPase (ERA) is a possible apoptosis regulator with RNA binding activity. Author(s): Akiyama T, Gohda J, Shibata S, Nomura Y, Azuma S, Ohmori Y, Sugano S, Arai H, Yamamoto T, Inoue J. Source: Genes to Cells : Devoted to Molecular & Cellular Mechanisms. 2001 November; 6(11): 987-1001. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11733036&dopt=Abstract

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Mechanisms of caffeine inhibition of DNA repair in E. coli. Author(s): Selby CP, Sancar A. Source: Prog Clin Biol Res. 1990; 340A: 179-93. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=2201972&dopt=Abstract

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Methylene blue sensitizes E. coli cells to X-rays. Author(s): Teixeira P, Menezes S. Source: International Journal of Radiation Biology. 1996 March; 69(3): 345-50. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=8613684&dopt=Abstract

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Midkine (MK), a retinoic acid (RA)-inducible gene product, produced in E. coli acts on neuronal and HL60 leukemia cells. Author(s): Maruta H, Bartlett PF, Nurcombe V, Nur-E-Kamal MS, Chomienne C, Muramatsu T, Muramatsu H, Fabri L, Nice E, Burgess AW. Source: Growth Factors (Chur, Switzerland). 1993; 8(2): 119-34. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=8466754&dopt=Abstract

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Minimal effects of E. coli and Erwinia asparaginase on the coagulation system in childhood acute lymphoblastic leukemia: a randomized study. Author(s): Risseeuw-Appel IM, Dekker I, Hop WC, Hahlen K. Source: Medical and Pediatric Oncology. 1994; 23(4): 335-43. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=8058004&dopt=Abstract

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Minimizing deletion mutagenesis artifact during Taq DNA polymerase PCR by E. coli SSB. Author(s): Chou Q. Source: Nucleic Acids Research. 1992 August 25; 20(16): 4371. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=1508731&dopt=Abstract

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Mitochondrial localization and oligomeric structure of HClpP, the human homologue of E. coli ClpP. Author(s): de Sagarra MR, Mayo I, Marco S, Rodriguez-Vilarino S, Oliva J, Carrascosa JL, Casta n JG. Source: Journal of Molecular Biology. 1999 October 1; 292(4): 819-25. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10525407&dopt=Abstract

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Molecular characterization of medium-chain acyl-CoA dehydrogenase (MCAD) deficiency: identification of a lys329 to glu mutation in the MCAD gene, and expression of inactive mutant enzyme protein in E. coli. Author(s): Gregersen N, Andresen BS, Bross P, Winter V, Rudiger N, Engst S, Christensen E, Kelly D, Strauss AW, Kolvraa S, et al. Source: Human Genetics. 1991 April; 86(6): 545-51. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=1902818&dopt=Abstract

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Molecular characterization of recombinant human acidic fibroblast growth factor produced in E. coli: comparative studies with human basic fibroblast growth factor. Author(s): Watanabe T, Seno M, Sasada R, Igarashi K. Source: Molecular Endocrinology (Baltimore, Md.). 1990 June; 4(6): 869-79. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=1700280&dopt=Abstract

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Molecular cloning of a new variant of human papillomavirus type 6 isolated from a Chinese woman and expression of its L1 gene in E. coli--molecular cloning & expression of HPV6 gene. Author(s): Shu LL, Feng HM, Jin Q, Hou YD. Source: Science in China. Series B, Chemistry, Life Sciences & Earth Sciences. 1992 May; 35(5): 585-91. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=1318719&dopt=Abstract

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Molecular cloning, expression, and regulation in Escherichia coli K-12 of a chromosome-mediated aerobactin iron transport system from a human invasive isolate of E. coli K1. Author(s): Valvano MA, Crosa JH. Source: Journal of Bacteriology. 1988 December; 170(12): 5529-38. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=3142849&dopt=Abstract

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Molecular epidemiological and phylogenetic associations of two novel putative virulence genes, iha and iroN(E. coli), among Escherichia coli isolates from patients with urosepsis. Author(s): Johnson JR, Russo TA, Tarr PI, Carlino U, Bilge SS, Vary JC Jr, Stell AL. Source: Infection and Immunity. 2000 May; 68(5): 3040-7. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10769012&dopt=Abstract

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Molecular epidemiology of 3 putative virulence genes for Escherichia coli urinary tract infection-usp, iha, and iroN(E. coli). Author(s): Bauer RJ, Zhang L, Foxman B, Siitonen A, Jantunen ME, Saxen H, Marrs CF. Source: The Journal of Infectious Diseases. 2002 May 15; 185(10): 1521-4. Epub 2002 April 30. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11992291&dopt=Abstract

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Mononuclear cells ingest E. coli opsonized by investigational intravenous immunoglobulin preparations in the absence of complement more efficiently than polymorphonuclear phagocytes. Author(s): Tinguely C, Schaller M, Nydegger UE. Source: Transfusion and Apheresis Science : Official Journal of the World Apheresis Association : Official Journal of the European Society for Haemapheresis. 2001 August; 25(1): 43-50. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11791761&dopt=Abstract

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More chaos on the microbiology front: the E. coli O157 outbreaks. Author(s): Rowbury RJ. Source: Sci Prog. 1997; 80 ( Pt 1): 3-4. No Abstract Available. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=9161124&dopt=Abstract

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Morphological study of the in vitro cytotoxic effect of alpha-hemolytic E. coli bacteria and culture supernatants on human blood granulocytes and monocytes. Author(s): Gadeberg OV, Blom J. Source: Acta Pathol Microbiol Immunol Scand [b]. 1986 April; 94(2): 75-83. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=3524113&dopt=Abstract

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Mutagenesis of human fibrinogen gamma chain 259-411 synthesized in E. coli: further characterization of the role of the disulfide bond CYS326-CYS339 in calcium binding. Author(s): Bolyard MG, Lord ST. Source: Biochemical and Biophysical Research Communications. 1991 January 31; 174(2): 853-60. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=1993077&dopt=Abstract

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Mutations in hns reduce the adherence of Shiga toxin-producing E. coli 091:H21 strain B2F1 to human colonic epithelial cells and increase the production of hemolysin. Author(s): Scott ME, Melton-Celsa AR, O'Brien AD. Source: Microbial Pathogenesis. 2003 March; 34(3): 155-9. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12631477&dopt=Abstract

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Mutations induced by saturated aqueous nitric oxide in the pSP189 supF gene in human Ad293 and E. coli MBM7070 cells. Author(s): Routledge MN, Wink DA, Keefer LK, Dipple A. Source: Carcinogenesis. 1993 July; 14(7): 1251-4. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=8330336&dopt=Abstract

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Naturally occurring anti-Kell stimulated by E. coli enterocolitis in a 20-day-old child. Author(s): Marsh WL, Nichols ME, Oyen R, Thayer RS, Deere WL, Freed PJ, Schmelter SE. Source: Transfusion. 1978 March-April; 18(2): 149-54. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=347643&dopt=Abstract

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Neonatal E. coli meningitis, hydrocephalus, respiratory distress syndrome, full recovery after temporary blindness. Author(s): Lorber J. Source: Proc R Soc Med. 1973 March; 66(3): 221-2. No Abstract Available. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=4572666&dopt=Abstract

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Neonatal E. coli pericarditis. Author(s): Wynn RJ. Source: Journal of Perinatal Medicine. 1979; 7(1): 23-6. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=370357&dopt=Abstract

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Neonatal fellowship. Group B streptococcal disease of a meconium pseudocyst in a neonate presenting with E. coli sepsis. Author(s): Goldstein M. Source: Journal of Perinatology : Official Journal of the California Perinatal Association. 1994 May-June; 14(3): 234-6. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=8064431&dopt=Abstract

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Neonatal mastitis due to E. coli. Author(s): Schwarz MD, Rosen RA. Source: Clinical Pediatrics. 1974 January; 13(1): 86. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=4588669&dopt=Abstract

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New perspectives on the role of Escherichia coli O157:H7 and other enterohaemorrhagic E. coli serotypes in human disease. Author(s): Goldwater PN, Bettelheim KA. Source: Journal of Medical Microbiology. 1998 December; 47(12): 1039-45. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=9856639&dopt=Abstract

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Nosocomial colonization and infection due to E. coli 0125:K70 epidemiologically linked to expressed breast-milk feedings. Author(s): Stiver HG, Albritton WL, Clark J, Friesen P, White FM. Source: Canadian Journal of Public Health. Revue Canadienne De Sante Publique. 1977 November-December; 68(6): 479-82. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=342078&dopt=Abstract

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Novel vectors for co-expression of two proteins in E. coli. Author(s): Kholod N, Mustelin T. Source: Biotechniques. 2001 August; 31(2): 322-3, 326-8. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11515368&dopt=Abstract

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Nucleotide excision repair: from E. coli to man. Author(s): Petit C, Sancar A. Source: Biochimie. 1999 January-February; 81(1-2): 15-25. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10214906&dopt=Abstract

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Nucleotide sequence and expression in E. coli of a human interferon-alpha gene selected from a genomic library using synthetic oligonucleotides. Author(s): Linnane AW, Beilharz MW, McMullen GL, Macreadie IG, Murphy M, Nisbet IT, Novitski CE, Woodrow GC. Source: Biochem Int. 1984 May; 8(5): 725-32. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=6089830&dopt=Abstract

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Nucleotide sequence and expression in E. coli of the complete P4 type VP4 from a G2 serotype human rotavirus. Author(s): Mahajan NP, Rao CD. Source: Archives of Virology. 1996; 141(2): 315-29. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=8634023&dopt=Abstract

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O antigen loss by semi-rough E. coli causing recurrent urinary infections, analysed by gel column filtration and gas-liquid chromatography. Author(s): Webb L, Goodwin CS, Green J. Source: Pathology. 1982 January; 14(1): 17-24. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=7043377&dopt=Abstract

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Observations concerning the pathogenesis of E. coli infections in mice. Author(s): Medearis DN Jr, Kenny JF. Source: Journal of Immunology (Baltimore, Md. : 1950). 1968 September; 101(3): 534-40. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=4877629&dopt=Abstract

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Occurrence and analysis of the composition of R factors in E. coli strains from urogenital infections for a period of one year. Author(s): Balazikova M, Krcmery V, Stepankova E. Source: J Hyg Epidemiol Microbiol Immunol. 1974; 18(2): 191-6. No Abstract Available. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=4606866&dopt=Abstract

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Occurrence and properties of hly-plasmids in E. coli from patients of the Berne area. Author(s): Gruenig HM, Lebek G. Source: Zentralbl Bakteriol Mikrobiol Hyg [a]. 1986 July; 261(4): 391-9. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=3020844&dopt=Abstract

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Occurrence of Enterobacteriaceae and E. coli in the intestine of the newborn by caesarean section. Author(s): Bezirtzoglou E, Romond C. Source: Acta Microbiol Bulg. 1990; 25: 76-81. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=2200243&dopt=Abstract

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O-grouping of urinary E. coli with the aid of fluorescent antibody technique. Author(s): Gnarpe H, Laurell G. Source: Acta Pathol Microbiol Scand. 1968; 72(3): 456-7. No Abstract Available. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=4870812&dopt=Abstract

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On the occurrence of serum antibodies to Bacteroides fragilis and serogroups of E. coli in patients with Crohn's disease. Author(s): Persson S, Danielsson D. Source: Scand J Infect Dis Suppl. 1979; (19): 61-7. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=88760&dopt=Abstract

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Oral administration of HSP-containing E. coli extract OM-89 has suppressive effects in autoimmunity. Regulation of autoimmune processes by modulating peripheral immunity towards hsp's? Author(s): Wendling U, Farine JC. Source: Biotherapy (Dordrecht, Netherlands). 1998; 10(3): 223-7. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=9559977&dopt=Abstract

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Oral gentamycin sulfate in treatment of infantile diarrhea due to enteropathogenic E. coli. Author(s): Martin GI. Source: Clinical Pediatrics. 1970 September; 9(9): 510-1. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=4916527&dopt=Abstract

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Outbreak of E. coli infection in Japan renews concerns. Author(s): Swinbanks D. Source: Nature. 1996 July 25; 382(6589): 290. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=8684449&dopt=Abstract

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Outbreak of enterocolitis caused by an enteroinvasive E. coli (serotype O 164, synonym serotype 147). Author(s): Neubauer M, Aldova E, Duben J. Source: Zentralbl Bakteriol Mikrobiol Hyg [a]. 1982 September; 252(4): 507-13. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=6758423&dopt=Abstract

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Outer membrane proteins of E. coli in the host-pathogen interaction in urinary tract infection. Author(s): Robledo JA, Serrano A, Domingue GJ. Source: The Journal of Urology. 1990 February; 143(2): 386-91. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=1688957&dopt=Abstract

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Overexpression and purification of eukaryotic transcription factors as glutathione-Stransferase fusions in E. coli. Author(s): Ford KG, Whitmarsh AJ, Hornby DP. Source: Methods in Molecular Biology (Clifton, N.J.). 1994; 30: 185-97. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=8004194&dopt=Abstract

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Overexpression of a human prostate-specific glandular kallikrein, hK2, in E. coli and generation of antibodies. Author(s): Saedi MS, Cass MM, Goel AS, Grauer L, Hogen KL, Okaneya T, Griffin BY, Klee GG, Young CY, Tindall DJ. Source: Molecular and Cellular Endocrinology. 1995 April 1; 109(2): 237-41. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=7664987&dopt=Abstract

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Overexpression of a partial human androgen receptor in E. coli: characterization of steroid binding, DNA binding, and immunological properties. Author(s): Young CY, Qiu SD, Prescott JL, Tindall DJ. Source: Molecular Endocrinology (Baltimore, Md.). 1990 December; 4(12): 1841-9. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=2127955&dopt=Abstract

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Overexpression of human cytosolic serine hydroxymethyltransferase in E. coli. Author(s): Renwick SB, Chave KJ, Sanders PG, Snell K. Source: Biochemical Society Transactions. 1995 November; 23(4): 624S. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=8654809&dopt=Abstract

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Over-expression of human DNA polymerase lambda in E. coli and characterization of the recombinant enzyme. Author(s): Shimazaki N, Yoshida K, Kobayashi T, Toji S, Tamai K, Koiwai O. Source: Genes to Cells : Devoted to Molecular & Cellular Mechanisms. 2002 July; 7(7): 639-51. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12081642&dopt=Abstract

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Over-expression of natural and variant human H-chain ferritins in E. coli. Author(s): Prozzi D, Crichton RR, Davison J. Source: Febs Letters. 1988 July 4; 234(1): 61-4. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=2839366&dopt=Abstract

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Overexpression of wild type and SeCys/Cys mutant of human thioredoxin reductase in E. coli: the role of selenocysteine in the catalytic activity. Author(s): Bar-Noy S, Gorlatov SN, Stadtman TC. Source: Free Radical Biology & Medicine. 2001 January 1; 30(1): 51-61. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11134895&dopt=Abstract

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Overproduction, preparation of monoclonal antibodies and purification of E. coli asparagine synthetase A. Author(s): Hinchman SK, Schuster SM. Source: Protein Engineering. 1992 April; 5(3): 279-83. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=1357656&dopt=Abstract

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Pancreatitis and E. coli O157:H7 colitis without hemolytic uremic syndrome. Author(s): Sass DA, Chopra KB, Regueiro MD. Source: Digestive Diseases and Sciences. 2003 February; 48(2): 415-6. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12643624&dopt=Abstract

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Pathogenicity islands of uropathogenic E. coli and evolution of virulence. Author(s): Blum-Oehler G, Dobrindt U, Janke B, Nagy G, Piechaczek K, Hacker J. Source: Advances in Experimental Medicine and Biology. 2000; 485: 25-32. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11109083&dopt=Abstract

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Pathogenicity islands of uropathogenic E. coli and the evolution of virulence. Author(s): Oelschlaeger TA, Dobrindt U, Hacker J. Source: International Journal of Antimicrobial Agents. 2002 June; 19(6): 517-21. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12135843&dopt=Abstract

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Persistent primary peritonitis due to group A streptococcus and E. coli. Author(s): Gavala A, Klimopulos S, Exarchos D, Konstantinidis K, Daniil Z, Zakynthinos SG, Zakynthinos E. Source: Intensive Care Medicine. 2002 December; 28(12): 1829-31. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12580167&dopt=Abstract

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Phylogenetic analysis of teneurin genes and comparison to the rearrangement hot spot elements of E. coli. Author(s): Minet AD, Chiquet-Ehrismann R. Source: Gene. 2000 October 17; 257(1): 87-97. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11054571&dopt=Abstract

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PKC zeta participates in activation of inflammatory response induced by enteropathogenic E. coli. Author(s): Savkovic SD, Koutsouris A, Hecht G. Source: American Journal of Physiology. Cell Physiology. 2003 September; 285(3): C51221. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12900386&dopt=Abstract

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Preparation of recombinant alpha2 antigen of M. leprae in E. coli and the application for sero-diagnosis of leprosy. Author(s): Yin Y, Suzuki Y, Makino M, Wu Q, Hou W. Source: Chinese Medical Sciences Journal = Chung-Kuo I Hsueh K'o Hsueh Tsa Chih / Chinese Academy of Medical Sciences. 1999 June; 14(2): 106. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12901619&dopt=Abstract

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Prevalence of HEp-2 cell-adherent Escherichia coli and characterisation of enteroaggregative E. coli and chain-like adherent E. coli isolated from children with and without diarrhoea, in Londrina, Brazil. Author(s): Gioppo NM, Elias WP Jr, Vidotto MC, Linhares RE, Saridakis HO, Gomes TA, Trabulsi LR, Pelayo JS. Source: Fems Microbiology Letters. 2000 September 15; 190(2): 293-8. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11034294&dopt=Abstract

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Prevention of recurrent urinary tract infections with immuno-active E. coli fractions: a meta-analysis of five placebo-controlled double-blind studies. Author(s): Bauer HW, Rahlfs VW, Lauener PA, Blessmann GS. Source: International Journal of Antimicrobial Agents. 2002 June; 19(6): 451-6. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12135831&dopt=Abstract

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Primary fecal culture used as template for PCR detection of diarrheagenic E. coli virulence factors. Author(s): da Silva Duque S, Silva RM, Sabra A, Campos LC. Source: Journal of Microbiological Methods. 2002 October; 51(2): 241-6. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12133616&dopt=Abstract

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Production of functional human selenocysteine-containing KDRF/thioredoxin reductase in E. coli. Author(s): Koishi R, Nakamura T, Takazawa T, Yoshimura C, Serizawa N. Source: Journal of Biochemistry. 2000 June; 127(6): 977-83. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10833265&dopt=Abstract

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Production of serum antibodies that recognise epitopes located on the R3 region of Escherichia coli core lipopolysaccharides by patients infected with strains of enterohaemorrhagic E. coli. Author(s): Chart H, Cheasty T, Willshaw GA. Source: Journal of Medical Microbiology. 2002 December; 51(12): 1050-4. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12466402&dopt=Abstract

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Prothrombotic risk factors in children with acute lymphoblastic leukemia treated with delayed E. coli asparaginase (COALL-92 and 97 protocols). Author(s): Mauz-Korholz C, Junker R, Gobel U, Nowak-Gottl U. Source: Thrombosis and Haemostasis. 2000 June; 83(6): 840-3. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10896235&dopt=Abstract

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Purification of recombinant chemokines from E. coli. Author(s): Proudfoot AE, Borlat F. Source: Methods in Molecular Biology (Clifton, N.J.). 2000; 138: 75-87. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10840744&dopt=Abstract

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Quantitation of E. coli protein impurities in recombinant human interferon-gamma. Author(s): Chen AB, Championsmith AA, Blanchard J, Gorrell J, Niepelt BA, Federici MM, Formento J, Sinicropi DV. Source: Applied Biochemistry and Biotechnology. 1992 August; 36(2): 137-52. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=1444359&dopt=Abstract

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Recombinant antitrypsin Pittsburgh undergoes proteolytic cleavage during E. coli sepsis and fails to prevent the associated coagulopathy in a primate model. Author(s): Harper PL, Taylor FB, DeLa Cadena RA, Courtney M, Colman RW, Carrell RW. Source: Thrombosis and Haemostasis. 1998 November; 80(5): 816-21. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=9843177&dopt=Abstract

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Recombinant E. coli efficiently delivers antigen and maturation signals to human dendritic cells: presentation of MART1 to CD8+ T cells. Author(s): Radford KJ, Jackson AM, Wang JH, Vassaux G, Lemoine NR. Source: International Journal of Cancer. Journal International Du Cancer. 2003 July 20; 105(6): 811-9. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12767067&dopt=Abstract

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Recombinant human single-chain MHC-peptide complexes made from E. coli By in vitro refolding: functional single-chain MHC-peptide complexes and tetramers with tumor associated antigens. Author(s): Denkberg G, Cohen CJ, Segal D, Kirkin AF, Reiter Y. Source: European Journal of Immunology. 2000 December; 30(12): 3522-32. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11093172&dopt=Abstract

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Recombinant IA-2 expressed in E. coli can be used for the routine detection of autoantibodies in Type-I diabetes. Author(s): Morgenthaler NG, Lobner K, Morgenthaler UY, Christie MR, Seissler J, Scherbaum WA. Source: Hormone and Metabolic Research. Hormon- Und Stoffwechselforschung. Hormones Et Metabolisme. 1998 September; 30(9): 559-64. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=9808324&dopt=Abstract

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Reconstitution of human 5-hydroxytryptamine5A receptor--G protein coupling in E. coli and Sf9 cell membranes with membranes from Sf9 cells expressing mammalian G proteins. Author(s): Francken BJ, Vanhauwe JF, Josson K, Jurzak M, Luyten WH, Leysen JE. Source: Receptors & Channels. 2001; 7(4): 303-18. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11697235&dopt=Abstract

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Recurrence of urinary tract infections in adult patients with community-acquired pyelonephritis caused by E. coli: a 1-year follow-up. Author(s): Karkkainen UM, Ikaheimo R, Katila ML, Siitonen A. Source: Scandinavian Journal of Infectious Diseases. 2000; 32(5): 495-9. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11055653&dopt=Abstract

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Refolding of protein inclusion bodies directly from E. coli homogenate using expanded bed adsorption chromatography. Author(s): Cho TH, Ahn SJ, Lee EK. Source: Bioseparation. 2001; 10(4-5): 189-96. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12233741&dopt=Abstract

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Release of ATP during host cell killing by enteropathogenic E. coli and its role as a secretory mediator. Author(s): Crane JK, Olson RA, Jones HM, Duffey ME. Source: American Journal of Physiology. Gastrointestinal and Liver Physiology. 2002 July; 283(1): G74-86. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12065294&dopt=Abstract

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Representational difference analysis between Afa/Dr diffusely adhering Escherichia coli and nonpathogenic E. coli K-12. Author(s): Blanc-Potard AB, Tinsley C, Scaletsky I, Le Bouguenec C, Guignot J, Servin AL, Nassif X, Bernet-Camard MF. Source: Infection and Immunity. 2002 October; 70(10): 5503-11. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12228276&dopt=Abstract

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Role of immunosuppression in the development of quinolone-resistant Escherichia coli spontaneous bacterial peritonitis and in the mortality of E. coli spontaneous bacterial peritonitis. Author(s): Cereto F, Molina I, Gonzalez A, Del Valle O, Esteban R, Guardia J, Genesca J. Source: Alimentary Pharmacology & Therapeutics. 2003 March 1; 17(5): 695-701. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12641519&dopt=Abstract

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Semi-automated fluorogenic PCR assays (TaqMan) forrapid detection of Escherichia coli O157:H7 and other shiga toxigenic E. coli. Author(s): Sharma VK, Dean-Nystrom EA, Casey TA. Source: Molecular and Cellular Probes. 1999 August; 13(4): 291-302. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10441202&dopt=Abstract

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Sensitisation of human carcinoma cells to the prodrug CB1954 by adenovirus vectormediated expression of E. coli nitroreductase. Author(s): Weedon SJ, Green NK, McNeish IA, Gilligan MG, Mautner V, Wrighton CJ, Mountain A, Young LS, Kerr DJ, Searle PF. Source: International Journal of Cancer. Journal International Du Cancer. 2000 June 15; 86(6): 848-54. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10842200&dopt=Abstract

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Sequence diversity of the Escherichia coli H7 fliC genes: implication for a DNAbased typing scheme for E. coli O157:H7. Author(s): Wang L, Rothemund D, Curd H, Reeves PR. Source: Journal of Clinical Microbiology. 2000 May; 38(5): 1786-90. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10790100&dopt=Abstract

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Sequence of the Escherichia coli O121 O-antigen gene cluster and detection of enterohemorrhagic E. coli O121 by PCR amplification of the wzx and wzy genes. Author(s): Fratamico PM, Briggs CE, Needle D, Chen CY, DebRoy C. Source: Journal of Clinical Microbiology. 2003 July; 41(7): 3379-83. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12843098&dopt=Abstract

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Spain's E. coli outbreak highlights mistakes. Author(s): Bosch X. Source: Lancet. 2000 November 11; 356(9242): 1665. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11089835&dopt=Abstract

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Specific proliferative and antibody responses of premature infants to intestinal colonization with nonpathogenic probiotic E. coli strain Nissle 1917. Author(s): Cukrowska B, LodInova-ZadnIkova R, Enders C, Sonnenborn U, Schulze J, Tlaskalova-Hogenova H. Source: Scandinavian Journal of Immunology. 2002 February; 55(2): 204-9. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11896937&dopt=Abstract

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Structural studies of human alkyladenine glycosylase and E. coli 3-methyladenine glycosylase. Author(s): Hollis T, Lau A, Ellenberger T. Source: Mutation Research. 2000 August 30; 460(3-4): 201-10. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10946229&dopt=Abstract

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Suicide gene therapy using E. coli beta-galactosidase. Author(s): Farquhar D, Pan BF, Sakurai M, Ghosh A, Mullen CA, Nelson JA. Source: Cancer Chemotherapy and Pharmacology. 2002 July; 50(1): 65-70. Epub 2002 June 08. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12111114&dopt=Abstract

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Surfactant protein A enhances the binding and deacylation of E. coli LPS by alveolar macrophages. Author(s): Stamme C, Wright JR. Source: The American Journal of Physiology. 1999 March; 276(3 Pt 1): L540-7. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10070120&dopt=Abstract

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Synthesis and characterization of the native anticodon domain of E. coli TRNA(Lys): simultaneous incorporation of modified nucleosides mnm(5)s(2)U, t(6)A, and pseudouridine using phosphoramidite chemistry. Author(s): Sundaram M, Crain PF, Davis DR. Source: The Journal of Organic Chemistry. 2000 September 8; 65(18): 5609-14. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10970299&dopt=Abstract

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Tails of two Tirs: actin pedestal formation by enteropathogenic E. coli and enterohemorrhagic E. coli O157:H7. Author(s): Campellone KG, Leong JM. Source: Current Opinion in Microbiology. 2003 February; 6(1): 82-90. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12615225&dopt=Abstract

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Testing of a Chemiluminescence Enzyme Immunoassay for selective detection of E. coli O157 from ground beef samples. Author(s): Kovacs HD, Rasky K. Source: Acta Vet Hung. 2001; 49(4): 377-83. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11942117&dopt=Abstract

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The 1.6 A crystal structure of E. coli argininosuccinate synthetase suggests a conformational change during catalysis. Author(s): Lemke CT, Howell PL. Source: Structure (Cambridge, Mass. : 2001). 2001 December; 9(12): 1153-64. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11738042&dopt=Abstract

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The admid system: generation of recombinant adenoviruses by Tn7-mediated transposition in E. coli. Author(s): Richards CA, Brown CE, Cogswell JP, Weiner MP. Source: Biotechniques. 2000 July; 29(1): 146-54. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10907089&dopt=Abstract

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The early postnatal development of salivary antibody and immunoglobulin response in children orally colonized with a nonpathogenic, probiotic strain of E. coli. Author(s): Vancikova Z, Lodinova-Zadnikova R, Radl J, Tlaskalova-Hogenova H. Source: Folia Microbiol (Praha). 2003; 48(2): 281-7. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12800517&dopt=Abstract

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The full-length, cytoplasmic C-terminus of the beta 2-adrenergic receptor expressed in E. coli acts as a substrate for phosphorylation by protein kinase A, insulin receptor tyrosine kinase, GRK2, but not protein kinase C and suppresses desensitization when expressed in vivo. Author(s): Doronin S, Lin F, Wang HY, Malbon CC. Source: Protein Expression and Purification. 2000 December; 20(3): 451-61. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11087685&dopt=Abstract

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The K1 capsule modulates trafficking of E. coli-containing vacuoles and enhances intracellular bacterial survival in human brain microvascular endothelial cells. Author(s): Kim KJ, Elliott SJ, Di Cello F, Stins MF, Kim KS. Source: Cellular Microbiology. 2003 April; 5(4): 245-52. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12675682&dopt=Abstract

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Three years experience of adults admitted to hospital in north-east Scotland with E. coli O157. Author(s): Cadwgan AM, Laing RB, Dargie L, Beadsworth M, Mackenzie AR, Douglas JG. Source: Scott Med J. 2002 October; 47(5): 112-4. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12469565&dopt=Abstract

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Three-dimensional structural views of damaged-DNA recognition: T4 endonuclease V, E. coli Vsr protein, and human nucleotide excision repair factor XPA. Author(s): Morikawa K, Shirakawa M. Source: Mutation Research. 2000 August 30; 460(3-4): 257-75. Review. Erratum In: Mutat Res 2001 April 4; 485(3): 267-8. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10946233&dopt=Abstract

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Transcriptional organisation and regulation of E. coli group 2 capsule expression. Author(s): Roberts IS. Source: Advances in Experimental Medicine and Biology. 2000; 485: 95-101. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11109092&dopt=Abstract

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Ultrastructure of cysts of E. coli. Author(s): Proctor EM, Gregory MA. Source: International Journal for Parasitology. 1974 April; 4(2): 125-31. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=4822480&dopt=Abstract

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Unexpected mortality from the use of E. coli L-asparaginase during remission induction therapy for childhood acute lymphoblastic leukemia: a report from the Taiwan Pediatric Oncology Group. Author(s): Liang DC, Hung IJ, Yang CP, Lin KH, Chen JS, Hsiao TC, Chang TT, Pui CH, Lee CH, Lin KS. Source: Leukemia : Official Journal of the Leukemia Society of America, Leukemia Research Fund, U.K. 1999 February; 13(2): 155-60. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10025887&dopt=Abstract

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Unsuccessful oral rehydration therapy in an infant with enteropathogenic E. coli diarrhoea. Studies of fluid and electrolyte homeostasis. Author(s): Marin L, Aperia A, Zetterstrom R, Gunoz H, Sokucu S, Saner G, Neyzi O. Source: Acta Paediatr Scand. 1985 May; 74(3): 477-9. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=3890466&dopt=Abstract

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Uropathogenic Escherichia coli are more likely than commensal E. coli to be shared between heterosexual sex partners. Author(s): Foxman B, Manning SD, Tallman P, Bauer R, Zhang L, Koopman JS, Gillespie B, Sobel JD, Marrs CF. Source: American Journal of Epidemiology. 2002 December 15; 156(12): 1133-40. Erratum In: Am J Epidemiol. 2003 August 15; 158(4): 396. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12480658&dopt=Abstract

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Usage of Aplysia lectin interactions with T antigen and poly-N-acetyllactosamine for screening of E. coli strains which bear glycoforms cross-reacting with cancerassociated antigens. Author(s): Gilboa-Garber N, Sudakevitz D. Source: Fems Immunology and Medical Microbiology. 2001 April; 30(3): 235-40. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11335144&dopt=Abstract

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Use of an improved E. coli method for the measurement of cobalamin in serum: comparison with the E. gracilis assay results. Author(s): Sourial NA. Source: Journal of Clinical Pathology. 1981 April; 34(4): 351-6. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=6787097&dopt=Abstract

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Use of human colostrum in the management of chronic infantile diarrhoea due to enteropathogenic E. coli infection with associated intestinal parasite infestations and undernutrition. Author(s): Saha K, Dua N, Chopra K. Source: Journal of Tropical Pediatrics. 1990 October; 36(5): 247-50. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=2126564&dopt=Abstract

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Using a eukaryotic GST fusion vector for proteins difficult to express in E. coli. Author(s): Tsai RY, Reed RR. Source: Biotechniques. 1997 November; 23(5): 794-6, 798, 800. No Abstract Available. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=9383538&dopt=Abstract

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Vaginal Escherichia coli share common virulence factor profiles, serotypes and phylogeny with other extraintestinal E. coli. Author(s): Obata-Yasuoka M, Ba-Thein W, Tsukamoto T, Yoshikawa H, Hayashi H. Source: Microbiology (Reading, England). 2002 September; 148(Pt 9): 2745-52. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12213921&dopt=Abstract

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Variable and constant regions in the C-terminus of vinculin and metavinculin. Cloning and expression of fragments in E. coli. Author(s): Strasser P, Gimona M, Herzog M, Geiger B, Small JV. Source: Febs Letters. 1993 February 15; 317(3): 189-94. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=8425604&dopt=Abstract

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Verotoxin-producing Escherichia coli (VTEC), enteropathogenic E. coli (EPEC) and necrotoxigenic E. coli (NTEC) isolated from healthy cattle in Spain. Author(s): Orden JA, Cid D, Ruiz-Santa-Quiteria JA, Garcia S, Martinez S, de la Fuente R. Source: Journal of Applied Microbiology. 2002; 93(1): 29-35. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12067371&dopt=Abstract

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Viability of, and transfer of a plasmid from, E. coli K12 in human intestine. Author(s): Anderson ES. Source: Nature. 1975 June 5; 255(5508): 502-4. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=1094298&dopt=Abstract

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Virulence factors in uropathogenic E. coli. Author(s): Shrikhande SN, Chande CA, Pathak AA. Source: Indian J Pathol Microbiol. 1999 July; 42(3): 321-5. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10862292&dopt=Abstract

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Virulence factors of Escherichia coli O157 and other Shiga toxin-producing E. coli. Author(s): Law D. Source: Journal of Applied Microbiology. 2000 May; 88(5): 729-45. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10792533&dopt=Abstract

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Virulence of wild-type E. coli uroisolates in experimental pyelonephritis. Author(s): Domingue GJ, Laucirica R, Baliga P, Covington S, Robledo JA, Li SC. Source: Kidney International. 1988 December; 34(6): 761-5. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=2905397&dopt=Abstract

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Was the E. coli 157 outbreak predictable? Author(s): Christopher P. Source: J R Soc Health. 1997 February; 117(1): 40. No Abstract Available. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=9050292&dopt=Abstract

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What's cooking with E. coli? The new, more sinister face of a familiar pathogen. Author(s): Woodhouse S. Source: Mlo: Medical Laboratory Observer. 2002 December; 34(12): 14-6, 19-20; Quiz 223. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12506847&dopt=Abstract

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CHAPTER 2. NUTRITION AND E. COLI Overview In this chapter, we will show you how to find studies dedicated specifically to nutrition and E. coli.

Finding Nutrition Studies on E. coli The National Institutes of Health’s Office of Dietary Supplements (ODS) offers a searchable bibliographic database called the IBIDS (International Bibliographic Information on Dietary Supplements; National Institutes of Health, Building 31, Room 1B29, 31 Center Drive, MSC 2086, Bethesda, Maryland 20892-2086, Tel: 301-435-2920, Fax: 301-480-1845, E-mail: [email protected]). The IBIDS contains over 460,000 scientific citations and summaries about dietary supplements and nutrition as well as references to published international, scientific literature on dietary supplements such as vitamins, minerals, and botanicals.7 The IBIDS includes references and citations to both human and animal research studies. As a service of the ODS, access to the IBIDS database is available free of charge at the following Web address: http://ods.od.nih.gov/databases/ibids.html. After entering the search area, you have three choices: (1) IBIDS Consumer Database, (2) Full IBIDS Database, or (3) Peer Reviewed Citations Only. Now that you have selected a database, click on the “Advanced” tab. An advanced search allows you to retrieve up to 100 fully explained references in a comprehensive format. Type “E. coli” (or synonyms) into the search box, and click “Go.” To narrow the search, you can also select the “Title” field.

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Adapted from http://ods.od.nih.gov. IBIDS is produced by the Office of Dietary Supplements (ODS) at the National Institutes of Health to assist the public, healthcare providers, educators, and researchers in locating credible, scientific information on dietary supplements. IBIDS was developed and will be maintained through an interagency partnership with the Food and Nutrition Information Center of the National Agricultural Library, U.S. Department of Agriculture.

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The following is a typical result when searching for recently indexed consumer information on E. coli: •

E. coli, Salmonella, Listeria, bacteria become unwelcome house guests. Source: Welland, D. Environmental-nutrition (USA). (October 1997). volume 20(10) page 1, 6.

Additional consumer oriented references include: •

A host-specific virulence protein of Erwinia herbicola pv. gyposophilae is translocated into human epithelial cells by the Type III secretion system of enteropathogenic Escherichia coli. Source: Valinsky, L. Nisan, I. Tu, X. Nisan, G. Rosenshine, I. Hanski, E. Barash, I. Manulis, S. Mol-plant-patho. Oxford, UK : Blackwell Science in collaboration with the British Society of Plant Pathology, c2000-. March 2002. volume 3 (2) page 97-101. 14646722

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Anchor-based design of improved cholera toxin and E. coli heat-labile enterotoxin receptor binding antagonists that display multiple binding modes. Author(s): Department of Biological Structure, Howard Hughes Medical Institute, University of Washington, Seattle, WA 98195, USA. Source: Pickens, Jason C Merritt, Ethan A Ahn, Misol Verlinde, Christophe L M J Hol, Wim G J Fan, Erkang Chem-Biol. 2002 February; 9(2): 215-24 1074-5521

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Animal health and foodborne pathogens: enterohaemorrhagic O157:H7 strains and other pathogenic Escherichia coli virotypes (EPEC, ETEC, EIEC, EHEC). Author(s): Department of Microbiology and Parasitology, Reference Laboratory of E. coli, Faculty of Veterinary in Lugo, University of Santiago de Compostela 27002 Lugo, Galiza, Spain. [email protected] Source: Gonzalez Garcia, E A Pol-J-Vet-Sci. 2002; 5(2): 103-15 1505-1773

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Artificial evolution of an enzyme active site: structural studies of three highly active mutants of Escherichia coli alkaline phosphatase. Author(s): Departement d'Ingenierie et d'Etudes des Proteines, CEA, Saclay, Gif-surYvette, France. [email protected] Source: Du, M H Le Lamoure, C Muller, B H Bulgakov, O V Lajeunesse, E Menez, A Boulain, J C J-Mol-Biol. 2002 March 1; 316(4): 941-53 0022-2836

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Binding of Escherichia coli ribosomal protein S8 to 16 S rRNA. A model for the interaction and the tertiary structure of the RNA binding site. Author(s): Laboratoire de Biochimie, Institut de Biologie Moleculaire et Cellulaire du CNRS, Strasbourg, France. Source: Mougel, M Eyermann, F Westhof, E Romby, P Expert Bezancon, A Ebel, J P Ehresmann, B Ehresmann, C J-Mol-Biol. 1987 November 5; 198(1): 91-107 0022-2836

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Binding specificity and the ligand dissociation process in the E. coli biotin holoenzyme synthetase. Author(s): Department of Chemistry and Biochemistry, College of Life Sciences, University of Maryland, College Park, Maryland 20472, USA. Source: Kwon, K Streaker, E D Beckett, D Protein-Sci. 2002 March; 11(3): 558-70 09618368

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Contribution of Lys276 to the conformational flexibility of the active site of glutamate decarboxylase from Escherichia coli. Author(s): Dipartimento di Scienze Biochimiche 'A. Rossi Fanelli' and Centro di Studio sulla Biologia Molecolare del CNR, Rome, Italy. [email protected] Source: Tramonti, A John, R A Bossa, F De Biase, D Eur-J-Biochem. 2002 October; 269(20): 4913-20 0014-2956

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Controlling E. coli O157. Source: Betts, G.D. Nutr-food-sci. Bradford, West Yorkshire, England : MCB University Press. July/October 2000. volume 30 (4/5) page 183-186. 0034-6659

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Designed potent multivalent chemoattractants for Escherichia coli. Author(s): Department of Chemistry, University of Wisconsin-Madison, Madison, WI 53706, USA. Source: Gestwicki, J E Strong, L E Borchardt, S L Cairo, C W Schnoes, A M Kiessling, L L Bioorg-Med-Chem. 2001 September; 9(9): 2387-93 0968-0896

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Detection of Shiga toxin-producing Escherichia coli by PCR in cattle in Argentina. Evaluation of two procedures. Author(s): Instituto de Biotecnologia, Centro Nacional de Investigaciones Agropecuarias, Instituto Nacional de Tecnologia Agropecuaria, Castelar, Argentina Source: Gioffre, A Meichtri, L Miliwebsky, E Baschkier, A Chillemi, G Romano, M I Sosa Estani, S Cataldi, A Rodriguez, R Rivas, M Vet-Microbiol. 2002 July 22; 87(4): 301-13 0378-1135

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Domain-domain interactions of HtpG, an Escherichia coli homologue of eukaryotic HSP90 molecular chaperone. Author(s): Department of Oral Biochemistry, Nagasaki University School of Dentistry, Nagasaki, Japan. [email protected] Source: Nemoto, T K Ono, T Kobayakawa, T Tanaka, E Baba, T T Tanaka, K Takagi, T Gotoh, T Eur-J-Biochem. 2001 October; 268(20): 5258-69 0014-2956

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Drosophila yolk protein produced in E. coli is accumulated by mosquito ovaries. Author(s): Institute of Cell and Molecular Biology, The University of Edinburgh, Edinburgh, UK. [email protected] Source: Bownes, M Hurd, H Busgen, T Servay, D Alvis, S Popovic, B Bruce, S Burns, I Rothwell, K Walkinshaw, M Insect-Mol-Biol. 2002 October; 11(5): 487-96 0962-1075

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Effect of selenium and vitamin E on antibody production by dairy cows vaccinated against Escherichia coli. Source: Panousis, N. Roubies, N. Karatzias, H. Frydas, S. Papasteriadis, A. Vet-rec. London : The British Veterinary Association. November 24, 2001. volume 149 (21) page 643-646. 0042-4900

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Expression and purification of the recombinant ConBr (Canavalia brasiliensis lectin) produced in Escherichia coli cells. Author(s): Depto. de Analises Clinicas e Toxicologicas, Universidade Federal do Ceara, Ceara, Brasil. Source: Nogueira, N A Grangeiro, M B da Cunha, R M Ramos, M V Alves, M A Teixeira, E H Barral Netto, M Calvete, J J Cavada, B S Grangeiro, T B Protein-Pept-Lett. 2002 February; 9(1): 59-66 0929-8665

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Ferric hydroxamate binding protein FhuD from Escherichia coli: mutants in conserved and non-conserved regions. Author(s): Department of Biological Sciences, University of Calgary, Alberta, Canada.

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Source: Clarke, T E Rohrbach, M R Tari, L W Vogel, H J Koster, W Biometals. 2002 June; 15(2): 121-31 0966-0844 •

Gene expression profiling of Escherichia coli growth transitions: an expanded stringent response model. Author(s): Advanced Center for Genome Technology, The University of Oklahoma, Norman, OK 73019-0245, USA. Source: Chang, D E Smalley, D J Conway, T Mol-Microbiol. 2002 July; 45(2): 289-306 0950-382X

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Growth, survival and heat resistance of Salmonella Typhimurium and Escherichia coli in regular and omega-3 hens egg products. Source: Hu, Y. Blank, G. Przybylski, R. Ismond, A. J-food-saf. Trumbull, Conn. : Food & Nutrition Press, Inc. December 2001. volume 21 (4) page 245-261. 0149-6085

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Insights into the reaction mechanism of Escherichia coli agmatinase by site-directed mutagenesis and molecular modelling. Author(s): Departamento de Biologia Molecular, Facultad de Ciencias Biologicas, Universidad de Concepcion, Casilla 160-C, Concepcion, Chile. Source: Salas, M Rodriguez, R Lopez, N Uribe, E Lopez, V Carvajal, N Eur-J-Biochem. 2002 November; 269(22): 5522-6 0014-2956

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Kinetic analysis of hydroxylation of saturated fatty acids by recombinant P450foxy produced by an Escherichia coli expression system. Author(s): Institute of Applied Biochemistry, University of Tsukuba, Tsukuba, Ibaraki, Japan. Source: Kitazume, Tatsuya Tanaka, Akinori Takaya, Naoki Nakamura, Akira Matsuyama, Shigeru Suzuki, Takahisa Shoun, Hirofumi Eur-J-Biochem. 2002 April; 269(8): 2075-82 0014-2956

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Ligand interactions and protein conformational changes of phosphopyridoxyl-labeled Escherichia coli phosphoenolpyruvate carboxykinase determined by fluorescence spectroscopy. Author(s): Departamento de Ciencias Quimicas, Facultad de Quimica y Biologia, Universidad de Santiago de Chile, Chile. [email protected] Source: Encinas, M V Gonzalez Nilo, F D Goldie, H Cardemil, E Eur-J-Biochem. 2002 October; 269(20): 4960-8 0014-2956

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NO-ergic mechanisms are implicated in a disturbed cardiac rhythm after systemic application of lipopolysaccharide E. coli to rats. Author(s): Institute of Physiology, National Academy of Sciences, Minsk, Belarus. [email protected] Source: Koulchitsky, S V Subbotin, O V Azev, O A Kulchitsky, V A Auton-Neurosci. 2002 June 28; 98(1-2): 99-101 1566-0702

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Nucleotide sequences of the major subunits of F9 and F12 fimbriae of uropathogenic Escherichia coli. Author(s): Department of Bacteriology, Faculty of Veterinary Medicine, University of Utrecht, The Netherlands. Source: Garcia, E Bergmans, H E van der Zeijst, B A Gaastra, W Microb-Pathog. 1992 August; 13(2): 161-6 0882-4010

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Oxidation of propionate to pyruvate in Escherichia coli. Involvement of methylcitrate dehydratase and aconitase. Author(s): Laboratorium fur Mikrobiologie, Fachbereich Biologie, Philipps-Universitat, Marburg, Germany.

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Source: Brock, M Maerker, C Schutz, A Volker, U Buckel, W Eur-J-Biochem. 2002 December; 269(24): 6184-94 0014-2956 •

Phosphoenolpyruvate-dependent phosphorylation site in enzyme IIIglc of the Escherichia coli phosphotransferase system. Source: Dorschug, M Frank, R Kalbitzer, H R Hengstenberg, W Deutscher, J Eur-JBiochem. 1984 October 1; 144(1): 113-9 0014-2956

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Photosensitization and mutation induced in Escherichia coli and Saccharomyces cerevisiae strains by dorstenin, a psoralen analog isolated from Dorstenia bahiensis. Author(s): EMBRAPA- Agroindustria de Alimentos, Rio de Janeiro, Brazil. Source: Lopes, D Oliveira, R R Kaplan, M A Lage, C S Leitao, A C Planta-Med. 2001 December; 67(9): 820-4 0032-0943

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Posttranslational modification of E. coli histone-like protein H-NS and bovine histones by short-chain poly-(R)-3-hydroxybutyrate (CPHB). Author(s): Department of Microbiology and Molecular Genetics, Michigan State University, East Lansing, MI 48824, USA. [email protected] Source: Reusch, R N Shabalin, O Crumbaugh, A Wagner, R Schroder, O Wurm, R FEBSLett. 2002 September 11; 527(1-3): 319-22 0014-5793

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Purification, reconstitution, and characterization of Na(+)/serine symporter, SstT, of Escherichia coli. Author(s): Department of Microbiology, Faculty of Pharmaceutical Sciences, Okayama University, Tsushima, Okayama 700-8530, Japan. Source: Kim, Y M Ogawa, W Tamai, E Kuroda, T Mizushima, T Tsuchiya, T J-Biochem(Tokyo). 2002 July; 132(1): 71-6 0021-924X

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Regulation of the Escherichia coli allantoin regulon: coordinated function of the repressor AllR and the activator AllS. Author(s): Department of Biochemistry, Faculty of Pharmacy, University of Barcelona, Avda. Diagonal 643, 08028 Barcelona, Spain. Source: Rintoul, M R Cusa, E Baldoma, L Badia, J Reitzer, L Aguilar, J J-Mol-Biol. 2002 December 6; 324(4): 599-610 0022-2836

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Replacement of Asp-162 by Ala prevents the cooperative transition by the substrates while enhancing the effect of the allosteric activator ATP on E. coli aspartate transcarbamoylase. Author(s): Laboratoire pour l'Utilisation du Rayonnement Electromagnetique (CNRS, CEA, MER), Universite Paris-Sud, F-91898 Orsay Cedex, France. Source: Fetler, L Tauc, P Baker, D P Macol, C P Kantrowitz, E R Vachette, P Protein-Sci. 2002 May; 11(5): 1074-81 0961-8368

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Single-chain ribosome inactivating proteins from plants depurinate Escherichia coli 23S ribosomal RNA. Author(s): Department of Biological Sciences, University of Warwick, Coventry, UK. Source: Hartley, M R Legname, G Osborn, R Chen, Z Lord, J M FEBS-Lett. 1991 September 23; 290(1-2): 65-8 0014-5793

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Solution conformations of unmodified and A(37)N(6)-dimethylallyl modified anticodon stem-loops of Escherichia coli tRNA(Phe). Author(s): Department of Biochemistry and Cell Biology, Rice University, Houston, TX 77251-1892, USA. Source: Cabello Villegas, Javier Winkler, Malcolm E Nikonowicz, Edward P J-Mol-Biol. 2002 June 21; 319(5): 1015-34 0022-2836

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Studies on the role of the metK gene product of Escherichia coli K-12. Author(s): Biology Department, Concordia University, 1455 de Maisonneuve Avenue, Montreal, Quebec H3G 1M8, Canada. Source: Wei, Yuhong Newman, E B Mol-Microbiol. 2002 March; 43(6): 1651-6 0950-382X

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The C-terminal domain of biotin protein ligase from E. coli is required for catalytic activity. Author(s): Department of Molecular Biosciences, University of Adelaide, South Australia 5005, Australia. [email protected] Source: Chapman Smith, A Mulhern, T D Whelan, F Cronan, J E Jr Wallace, J C ProteinSci. 2001 December; 10(12): 2608-17 0961-8368

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The effectiveness of an Escherichia coli phytase in improving phosphorus and calcium bioavailabilities in poultry and young pigs. Author(s): Institute of Animal Nutrition, Faculty of Veterinary Medicine, Free University, Berlin, Germany. Source: Igbasan, F A Simon, O Miksch, G Manner, K Arch-Tierernahr. 2001; 54(2): 117-26 0003-942X

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The PLP-dependent biotin synthase from Escherichia coli: mechanistic studies. Author(s): Laboratoire de Chimie et Biochimie des Centres Redox Biologiques, DRDCCB, CEA/CNRS/Universite Joseph Fourier, UMR 5047, 17 Avenue des Martyrs, 38054 Cedex 09, Grenoble, France Source: Ollagnier de Choudens, S Mulliez, E Fontecave, M FEBS-Lett. 2002 December 18; 532(3): 465-8 0014-5793

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The role of the Zn(II) binding domain in the mechanism of E. coli DNA topoisomerase I. Author(s): Department of Biochemistry and Molecular Biology, New York Medical College, Valhalla, NY, USA. [email protected] Source: Ahumada, A Tse Dinh, Y C BMC-Biochem. 2002 May 29; 3(1): 13 1471-2091

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Three-dimensional model of Escherichia coli ribosomal 5 S RNA as deduced from structure probing in solution and computer modeling. Author(s): Institut de Biologie Moleculaire et Cellulaire de CNRS, Strasbourg, France. Source: Brunel, C Romby, P Westhof, E Ehresmann, C Ehresmann, B J-Mol-Biol. 1991 September 5; 221(1): 293-308 0022-2836

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Uracil-initiated base excision DNA repair synthesis fidelity in human colon adenocarcinoma LoVo and Escherichia coli cell extracts. Author(s): Department of Biochemistry and Biophysics, Oregon State University, Corvallis, Oregon 97331, USA. Source: Sanderson, R J Bennett, S E Sung, J S Mosbaugh, D W Prog-Nucleic-Acid-ResMol-Biol. 2001; 68: 165-88 0079-6603

The following information is typical of that found when using the “Full IBIDS Database” to search for “E. coli” (or a synonym): •

Effect of dietary zinc on growth and immune response of piglets orally challenged with E. coli K88. Author(s): Bologna Univ. (Italy). Dipartimento di Protezione e Valorizzazione Agroalimentare Istituto Zooprofilattico Sperimentale della Lombardia e dell' Emilia, Brescia (Italy) Source: Bosi, P. Casini, L. Gremokolini, C. Piattoni, F. Perini, S. Proceedings-of-theASPA-Congress-Recent-Progress-in-Animal-Production-Science (Italy). (2001). volume 2 page 338-340.

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Isolation and partial characterization of an antibacterial substance produced by Enterococcus faecium. Author(s): University of Sofia (Bulgaria). Dept. of Microbiology Source: Pantev, A. Kabadjova, P. Ivanova, I. Dalgalarrondo, M. Haertle, T. Dousset, X. Prevost, H. Chobert, J. M. Folia-Microbiologica (Czech Republic). (August 2002). volume 47(4) page 391-400.

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The use of Kluyveromyces m. and Bifidobacterium suis in the diet of piglets E. coli K88 challenged or not. Author(s): Bologna Univ. (Italy). Dipartimento di Protezione e Valorizzazione Agroalimentare Policlinico S. Matteo, Pavia (Italy) Bologna Univ. (Italy). Istituto di Microbiologia Agraria e Tecnica Istituto Zooprofilattico Sperimentale della Lombardia e dell' Emilia, Brescia (Italy) Source: Gremokolini, C. Casini, L. Bosi, P. Avanzini, A. Biavati, B. Merialdi, G. Proceedings-of-the-ASPA-Congress-Recent-Progress-in-Animal-Production-Science (Italy). (2001). volume 2 page 335-337.

Additional physician-oriented references include: •

A host-specific virulence protein of Erwinia herbicola pv. gyposophilae is translocated into human epithelial cells by the Type III secretion system of enteropathogenic Escherichia coli. Source: Valinsky, L. Nisan, I. Tu, X. Nisan, G. Rosenshine, I. Hanski, E. Barash, I. Manulis, S. Mol-plant-patho. Oxford, UK : Blackwell Science in collaboration with the British Society of Plant Pathology, c2000-. March 2002. volume 3 (2) page 97-101. 14646722

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Anchor-based design of improved cholera toxin and E. coli heat-labile enterotoxin receptor binding antagonists that display multiple binding modes. Author(s): Department of Biological Structure, Howard Hughes Medical Institute, University of Washington, Seattle, WA 98195, USA. Source: Pickens, Jason C Merritt, Ethan A Ahn, Misol Verlinde, Christophe L M J Hol, Wim G J Fan, Erkang Chem-Biol. 2002 February; 9(2): 215-24 1074-5521

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Animal health and foodborne pathogens: enterohaemorrhagic O157:H7 strains and other pathogenic Escherichia coli virotypes (EPEC, ETEC, EIEC, EHEC). Author(s): Department of Microbiology and Parasitology, Reference Laboratory of E. coli, Faculty of Veterinary in Lugo, University of Santiago de Compostela 27002 Lugo, Galiza, Spain. [email protected] Source: Gonzalez Garcia, E A Pol-J-Vet-Sci. 2002; 5(2): 103-15 1505-1773

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Artificial evolution of an enzyme active site: structural studies of three highly active mutants of Escherichia coli alkaline phosphatase. Author(s): Departement d'Ingenierie et d'Etudes des Proteines, CEA, Saclay, Gif-surYvette, France. [email protected] Source: Du, M H Le Lamoure, C Muller, B H Bulgakov, O V Lajeunesse, E Menez, A Boulain, J C J-Mol-Biol. 2002 March 1; 316(4): 941-53 0022-2836

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Binding of Escherichia coli ribosomal protein S8 to 16 S rRNA. A model for the interaction and the tertiary structure of the RNA binding site. Author(s): Laboratoire de Biochimie, Institut de Biologie Moleculaire et Cellulaire du CNRS, Strasbourg, France. Source: Mougel, M Eyermann, F Westhof, E Romby, P Expert Bezancon, A Ebel, J P Ehresmann, B Ehresmann, C J-Mol-Biol. 1987 November 5; 198(1): 91-107 0022-2836

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Binding specificity and the ligand dissociation process in the E. coli biotin holoenzyme synthetase. Author(s): Department of Chemistry and Biochemistry, College of Life Sciences, University of Maryland, College Park, Maryland 20472, USA. Source: Kwon, K Streaker, E D Beckett, D Protein-Sci. 2002 March; 11(3): 558-70 09618368

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Contribution of Lys276 to the conformational flexibility of the active site of glutamate decarboxylase from Escherichia coli. Author(s): Dipartimento di Scienze Biochimiche 'A. Rossi Fanelli' and Centro di Studio sulla Biologia Molecolare del CNR, Rome, Italy. [email protected] Source: Tramonti, A John, R A Bossa, F De Biase, D Eur-J-Biochem. 2002 October; 269(20): 4913-20 0014-2956

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Controlling E. coli O157. Source: Betts, G.D. Nutr-food-sci. Bradford, West Yorkshire, England : MCB University Press. July/October 2000. volume 30 (4/5) page 183-186. 0034-6659

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Designed potent multivalent chemoattractants for Escherichia coli. Author(s): Department of Chemistry, University of Wisconsin-Madison, Madison, WI 53706, USA. Source: Gestwicki, J E Strong, L E Borchardt, S L Cairo, C W Schnoes, A M Kiessling, L L Bioorg-Med-Chem. 2001 September; 9(9): 2387-93 0968-0896

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Detection of Shiga toxin-producing Escherichia coli by PCR in cattle in Argentina. Evaluation of two procedures. Author(s): Instituto de Biotecnologia, Centro Nacional de Investigaciones Agropecuarias, Instituto Nacional de Tecnologia Agropecuaria, Castelar, Argentina Source: Gioffre, A Meichtri, L Miliwebsky, E Baschkier, A Chillemi, G Romano, M I Sosa Estani, S Cataldi, A Rodriguez, R Rivas, M Vet-Microbiol. 2002 July 22; 87(4): 301-13 0378-1135

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Domain-domain interactions of HtpG, an Escherichia coli homologue of eukaryotic HSP90 molecular chaperone. Author(s): Department of Oral Biochemistry, Nagasaki University School of Dentistry, Nagasaki, Japan. [email protected] Source: Nemoto, T K Ono, T Kobayakawa, T Tanaka, E Baba, T T Tanaka, K Takagi, T Gotoh, T Eur-J-Biochem. 2001 October; 268(20): 5258-69 0014-2956

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Drosophila yolk protein produced in E. coli is accumulated by mosquito ovaries. Author(s): Institute of Cell and Molecular Biology, The University of Edinburgh, Edinburgh, UK. [email protected] Source: Bownes, M Hurd, H Busgen, T Servay, D Alvis, S Popovic, B Bruce, S Burns, I Rothwell, K Walkinshaw, M Insect-Mol-Biol. 2002 October; 11(5): 487-96 0962-1075

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Effect of selenium and vitamin E on antibody production by dairy cows vaccinated against Escherichia coli. Source: Panousis, N. Roubies, N. Karatzias, H. Frydas, S. Papasteriadis, A. Vet-rec. London : The British Veterinary Association. November 24, 2001. volume 149 (21) page 643-646. 0042-4900

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Expression and purification of the recombinant ConBr (Canavalia brasiliensis lectin) produced in Escherichia coli cells. Author(s): Depto. de Analises Clinicas e Toxicologicas, Universidade Federal do Ceara, Ceara, Brasil.

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Source: Nogueira, N A Grangeiro, M B da Cunha, R M Ramos, M V Alves, M A Teixeira, E H Barral Netto, M Calvete, J J Cavada, B S Grangeiro, T B Protein-Pept-Lett. 2002 February; 9(1): 59-66 0929-8665 •

Ferric hydroxamate binding protein FhuD from Escherichia coli: mutants in conserved and non-conserved regions. Author(s): Department of Biological Sciences, University of Calgary, Alberta, Canada. Source: Clarke, T E Rohrbach, M R Tari, L W Vogel, H J Koster, W Biometals. 2002 June; 15(2): 121-31 0966-0844

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Gene expression profiling of Escherichia coli growth transitions: an expanded stringent response model. Author(s): Advanced Center for Genome Technology, The University of Oklahoma, Norman, OK 73019-0245, USA. Source: Chang, D E Smalley, D J Conway, T Mol-Microbiol. 2002 July; 45(2): 289-306 0950-382X

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Growth, survival and heat resistance of Salmonella Typhimurium and Escherichia coli in regular and omega-3 hens egg products. Source: Hu, Y. Blank, G. Przybylski, R. Ismond, A. J-food-saf. Trumbull, Conn. : Food & Nutrition Press, Inc. December 2001. volume 21 (4) page 245-261. 0149-6085

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Insights into the reaction mechanism of Escherichia coli agmatinase by site-directed mutagenesis and molecular modelling. Author(s): Departamento de Biologia Molecular, Facultad de Ciencias Biologicas, Universidad de Concepcion, Casilla 160-C, Concepcion, Chile. Source: Salas, M Rodriguez, R Lopez, N Uribe, E Lopez, V Carvajal, N Eur-J-Biochem. 2002 November; 269(22): 5522-6 0014-2956

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Kinetic analysis of hydroxylation of saturated fatty acids by recombinant P450foxy produced by an Escherichia coli expression system. Author(s): Institute of Applied Biochemistry, University of Tsukuba, Tsukuba, Ibaraki, Japan. Source: Kitazume, Tatsuya Tanaka, Akinori Takaya, Naoki Nakamura, Akira Matsuyama, Shigeru Suzuki, Takahisa Shoun, Hirofumi Eur-J-Biochem. 2002 April; 269(8): 2075-82 0014-2956

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Ligand interactions and protein conformational changes of phosphopyridoxyl-labeled Escherichia coli phosphoenolpyruvate carboxykinase determined by fluorescence spectroscopy. Author(s): Departamento de Ciencias Quimicas, Facultad de Quimica y Biologia, Universidad de Santiago de Chile, Chile. [email protected] Source: Encinas, M V Gonzalez Nilo, F D Goldie, H Cardemil, E Eur-J-Biochem. 2002 October; 269(20): 4960-8 0014-2956

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NO-ergic mechanisms are implicated in a disturbed cardiac rhythm after systemic application of lipopolysaccharide E. coli to rats. Author(s): Institute of Physiology, National Academy of Sciences, Minsk, Belarus. [email protected] Source: Koulchitsky, S V Subbotin, O V Azev, O A Kulchitsky, V A Auton-Neurosci. 2002 June 28; 98(1-2): 99-101 1566-0702

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Nucleotide sequences of the major subunits of F9 and F12 fimbriae of uropathogenic Escherichia coli. Author(s): Department of Bacteriology, Faculty of Veterinary Medicine, University of Utrecht, The Netherlands.

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Source: Garcia, E Bergmans, H E van der Zeijst, B A Gaastra, W Microb-Pathog. 1992 August; 13(2): 161-6 0882-4010 •

Oxidation of propionate to pyruvate in Escherichia coli. Involvement of methylcitrate dehydratase and aconitase. Author(s): Laboratorium fur Mikrobiologie, Fachbereich Biologie, Philipps-Universitat, Marburg, Germany. Source: Brock, M Maerker, C Schutz, A Volker, U Buckel, W Eur-J-Biochem. 2002 December; 269(24): 6184-94 0014-2956

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Phosphoenolpyruvate-dependent phosphorylation site in enzyme IIIglc of the Escherichia coli phosphotransferase system. Source: Dorschug, M Frank, R Kalbitzer, H R Hengstenberg, W Deutscher, J Eur-JBiochem. 1984 October 1; 144(1): 113-9 0014-2956

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Photosensitization and mutation induced in Escherichia coli and Saccharomyces cerevisiae strains by dorstenin, a psoralen analog isolated from Dorstenia bahiensis. Author(s): EMBRAPA- Agroindustria de Alimentos, Rio de Janeiro, Brazil. Source: Lopes, D Oliveira, R R Kaplan, M A Lage, C S Leitao, A C Planta-Med. 2001 December; 67(9): 820-4 0032-0943

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Posttranslational modification of E. coli histone-like protein H-NS and bovine histones by short-chain poly-(R)-3-hydroxybutyrate (CPHB). Author(s): Department of Microbiology and Molecular Genetics, Michigan State University, East Lansing, MI 48824, USA. [email protected] Source: Reusch, R N Shabalin, O Crumbaugh, A Wagner, R Schroder, O Wurm, R FEBSLett. 2002 September 11; 527(1-3): 319-22 0014-5793

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Purification, reconstitution, and characterization of Na(+)/serine symporter, SstT, of Escherichia coli. Author(s): Department of Microbiology, Faculty of Pharmaceutical Sciences, Okayama University, Tsushima, Okayama 700-8530, Japan. Source: Kim, Y M Ogawa, W Tamai, E Kuroda, T Mizushima, T Tsuchiya, T J-Biochem(Tokyo). 2002 July; 132(1): 71-6 0021-924X

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Regulation of the Escherichia coli allantoin regulon: coordinated function of the repressor AllR and the activator AllS. Author(s): Department of Biochemistry, Faculty of Pharmacy, University of Barcelona, Avda. Diagonal 643, 08028 Barcelona, Spain. Source: Rintoul, M R Cusa, E Baldoma, L Badia, J Reitzer, L Aguilar, J J-Mol-Biol. 2002 December 6; 324(4): 599-610 0022-2836

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Replacement of Asp-162 by Ala prevents the cooperative transition by the substrates while enhancing the effect of the allosteric activator ATP on E. coli aspartate transcarbamoylase. Author(s): Laboratoire pour l'Utilisation du Rayonnement Electromagnetique (CNRS, CEA, MER), Universite Paris-Sud, F-91898 Orsay Cedex, France. Source: Fetler, L Tauc, P Baker, D P Macol, C P Kantrowitz, E R Vachette, P Protein-Sci. 2002 May; 11(5): 1074-81 0961-8368

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Single-chain ribosome inactivating proteins from plants depurinate Escherichia coli 23S ribosomal RNA. Author(s): Department of Biological Sciences, University of Warwick, Coventry, UK. Source: Hartley, M R Legname, G Osborn, R Chen, Z Lord, J M FEBS-Lett. 1991 September 23; 290(1-2): 65-8 0014-5793

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Solution conformations of unmodified and A(37)N(6)-dimethylallyl modified anticodon stem-loops of Escherichia coli tRNA(Phe). Author(s): Department of Biochemistry and Cell Biology, Rice University, Houston, TX 77251-1892, USA. Source: Cabello Villegas, Javier Winkler, Malcolm E Nikonowicz, Edward P J-Mol-Biol. 2002 June 21; 319(5): 1015-34 0022-2836

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Studies on the role of the metK gene product of Escherichia coli K-12. Author(s): Biology Department, Concordia University, 1455 de Maisonneuve Avenue, Montreal, Quebec H3G 1M8, Canada. Source: Wei, Yuhong Newman, E B Mol-Microbiol. 2002 March; 43(6): 1651-6 0950-382X

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The C-terminal domain of biotin protein ligase from E. coli is required for catalytic activity. Author(s): Department of Molecular Biosciences, University of Adelaide, South Australia 5005, Australia. [email protected] Source: Chapman Smith, A Mulhern, T D Whelan, F Cronan, J E Jr Wallace, J C ProteinSci. 2001 December; 10(12): 2608-17 0961-8368

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The effectiveness of an Escherichia coli phytase in improving phosphorus and calcium bioavailabilities in poultry and young pigs. Author(s): Institute of Animal Nutrition, Faculty of Veterinary Medicine, Free University, Berlin, Germany. Source: Igbasan, F A Simon, O Miksch, G Manner, K Arch-Tierernahr. 2001; 54(2): 117-26 0003-942X

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The PLP-dependent biotin synthase from Escherichia coli: mechanistic studies. Author(s): Laboratoire de Chimie et Biochimie des Centres Redox Biologiques, DRDCCB, CEA/CNRS/Universite Joseph Fourier, UMR 5047, 17 Avenue des Martyrs, 38054 Cedex 09, Grenoble, France Source: Ollagnier de Choudens, S Mulliez, E Fontecave, M FEBS-Lett. 2002 December 18; 532(3): 465-8 0014-5793

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The role of the Zn(II) binding domain in the mechanism of E. coli DNA topoisomerase I. Author(s): Department of Biochemistry and Molecular Biology, New York Medical College, Valhalla, NY, USA. [email protected] Source: Ahumada, A Tse Dinh, Y C BMC-Biochem. 2002 May 29; 3(1): 13 1471-2091

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Three-dimensional model of Escherichia coli ribosomal 5 S RNA as deduced from structure probing in solution and computer modeling. Author(s): Institut de Biologie Moleculaire et Cellulaire de CNRS, Strasbourg, France. Source: Brunel, C Romby, P Westhof, E Ehresmann, C Ehresmann, B J-Mol-Biol. 1991 September 5; 221(1): 293-308 0022-2836

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Uracil-initiated base excision DNA repair synthesis fidelity in human colon adenocarcinoma LoVo and Escherichia coli cell extracts. Author(s): Department of Biochemistry and Biophysics, Oregon State University, Corvallis, Oregon 97331, USA. Source: Sanderson, R J Bennett, S E Sung, J S Mosbaugh, D W Prog-Nucleic-Acid-ResMol-Biol. 2001; 68: 165-88 0079-6603

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Federal Resources on Nutrition In addition to the IBIDS, the United States Department of Health and Human Services (HHS) and the United States Department of Agriculture (USDA) provide many sources of information on general nutrition and health. Recommended resources include: •

healthfinder®, HHS’s gateway to health information, including diet and nutrition: http://www.healthfinder.gov/scripts/SearchContext.asp?topic=238&page=0

•

The United States Department of Agriculture’s Web site dedicated to nutrition information: www.nutrition.gov

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The Food and Drug Administration’s Web site for federal food safety information: www.foodsafety.gov

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The National Action Plan on Overweight and Obesity sponsored by the United States Surgeon General: http://www.surgeongeneral.gov/topics/obesity/

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The Center for Food Safety and Applied Nutrition has an Internet site sponsored by the Food and Drug Administration and the Department of Health and Human Services: http://vm.cfsan.fda.gov/

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Center for Nutrition Policy and Promotion sponsored by the United States Department of Agriculture: http://www.usda.gov/cnpp/

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Food and Nutrition Information Center, National Agricultural Library sponsored by the United States Department of Agriculture: http://www.nal.usda.gov/fnic/

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Food and Nutrition Service sponsored by the United States Department of Agriculture: http://www.fns.usda.gov/fns/

Additional Web Resources A number of additional Web sites offer encyclopedic information covering food and nutrition. The following is a representative sample: •

AOL: http://search.aol.com/cat.adp?id=174&layer=&from=subcats

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Family Village: http://www.familyvillage.wisc.edu/med_nutrition.html

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Google: http://directory.google.com/Top/Health/Nutrition/

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Healthnotes: http://www.healthnotes.com/

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Open Directory Project: http://dmoz.org/Health/Nutrition/

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Yahoo.com: http://dir.yahoo.com/Health/Nutrition/

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WebMDHealth: http://my.webmd.com/nutrition

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WholeHealthMD.com: http://www.wholehealthmd.com/reflib/0,1529,00.html

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The following is a specific Web list relating to E. coli; please note that any particular subject below may indicate either a therapeutic use, or a contraindication (potential danger), and does not reflect an official recommendation: •

Food and Diet Berries Source: Healthnotes, Inc.; www.healthnotes.com Juices Source: Healthnotes, Inc.; www.healthnotes.com

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CHAPTER 3. ALTERNATIVE MEDICINE AND E. COLI Overview In this chapter, we will begin by introducing you to official information sources on complementary and alternative medicine (CAM) relating to E. coli. At the conclusion of this chapter, we will provide additional sources.

National Center for Complementary and Alternative Medicine The National Center for Complementary and Alternative Medicine (NCCAM) of the National Institutes of Health (http://nccam.nih.gov/) has created a link to the National Library of Medicine’s databases to facilitate research for articles that specifically relate to E. coli and complementary medicine. To search the database, go to the following Web site: http://www.nlm.nih.gov/nccam/camonpubmed.html. Select “CAM on PubMed.” Enter “E. coli” (or synonyms) into the search box. Click “Go.” The following references provide information on particular aspects of complementary and alternative medicine that are related to E. coli: •

Acid tolerance and gad mRNA levels of Escherichia coli O157:H7 grown in foods. Author(s): Yokoigawa K, Takikawa A, Okubo Y, Umesako S. Source: International Journal of Food Microbiology. 2003 May 15; 82(3): 203-11. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12593923&dopt=Abstract

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Amelioration of murine colitis by feeding a solution of lysed Escherichia coli. Author(s): Konrad A, Mahler M, Flogerzi B, Kalousek MB, Lange J, Varga L, Seibold F. Source: Scandinavian Journal of Gastroenterology. 2003 February; 38(2): 172-9. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12678334&dopt=Abstract

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Animal issues associated with Escherichia coli O157:H7. Author(s): Sanchez S, Lee MD, Harmon BG, Maurer JJ, Doyle MP.

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Source: J Am Vet Med Assoc. 2002 October 15; 221(8): 1122-6. Review. No Abstract Available. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12387380&dopt=Abstract •

Antibiotic resistance among verocytotoxigenic Escherichia coli (VTEC) and nonVTEC isolated from domestic animals and humans. Author(s): Bettelheim KA, Hornitzky MA, Djordjevic SP, Kuzevski A. Source: Journal of Medical Microbiology. 2003 February; 52(Pt 2): 155-62. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12543922&dopt=Abstract

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Bacterial deconjugation of arbutin by Escherichia coli. Author(s): Siegers C, Bodinet C, Ali SS, Siegers CP. Source: Phytomedicine : International Journal of Phytotherapy and Phytopharmacology. 2003; 10 Suppl 4: 58-60. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12807345&dopt=Abstract

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Bactericidal activities of plant essential oils and some of their isolated constituents against Campylobacter jejuni, Escherichia coli, Listeria monocytogenes, and Salmonella enterica. Author(s): Friedman M, Henika PR, Mandrell RE. Source: J Food Prot. 2002 October; 65(10): 1545-60. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12380738&dopt=Abstract

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Behavior of enteroaggregative Escherichia coli in bottled spring and mineral water. Author(s): Vasudevan P, Annamalai T, Sartori L, Hoagland T, Venkitanarayanan K. Source: J Food Prot. 2003 March; 66(3): 497-500. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12636308&dopt=Abstract

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Characterization of up-regulated proteases in an industrial recombinant Escherichia coli fermentation. Author(s): Jordan GL, Harcum SW. Source: Journal of Industrial Microbiology & Biotechnology. 2002 February; 28(2): 74-80. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12074055&dopt=Abstract

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Cytokine release of whole blood from adult female donors challenged with mistletoe lectin-1 standardised mistletoe extract and E. coli endotoxin or phytohaemagglutinin (PHA). Author(s): Braun JM, Blackwell CC, Weir DM, Beuth J. Source: Anticancer Res. 2003 March-April; 23(2B): 1349-52. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12820393&dopt=Abstract

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Death of Salmonella, Escherichia coli O157:H7, and Listeria monocytogenes in garlic butter as affected by storage temperature. Author(s): Adler BB, Beuchat LR. Source: J Food Prot. 2002 December; 65(12): 1976-80. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12495019&dopt=Abstract

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Detection of Escherichia coli O157:H7 bacteria by a combination of immunofluorescent staining and capillary electrophoresis. Author(s): Kourkine IV, Ristic-Petrovic M, Davis E, Ruffolo CG, Kapsalis A, Barron AE. Source: Electrophoresis. 2003 February; 24(4): 655-61. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12601734&dopt=Abstract

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Diet influences the ecology of lactic acid bacteria and Escherichia coli along the digestive tract of cattle: neural networks and 16S rDNA. Author(s): Krause DO, Smith WJ, Conlan LL, Gough JM, Williamson MA, McSweeney CS. Source: Microbiology (Reading, England). 2003 January; 149(Pt 1): 57-65. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12576580&dopt=Abstract

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Differences in antibiotic resistance in Escherichia coli, isolated from East-European swine herds with or without prophylactic use of antibiotics. Author(s): Docic M, Bilkei G. Source: Journal of Veterinary Medicine. B, Infectious Diseases and Veterinary Public Health. 2003 February; 50(1): 27-30. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12710497&dopt=Abstract

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Drug toxicity in E. coli cells expressing human topoisomerase I. Author(s): Taylor ST, Menzel R. Source: Methods in Molecular Biology (Clifton, N.J.). 2001; 95: 195-204. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11089232&dopt=Abstract

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Effect of a lipopolysaccharide from E. coli on the proliferation of fibroblasts and keratinocytes in vitro. Author(s): Yang H, Kaneko M, He C, Hughes MA, Cherry GW. Source: Phytotherapy Research : Ptr. 2002 February; 16(1): 43-7. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11807964&dopt=Abstract

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Effect of acupuncture in the treatment of young pigs with induced Escherichia coli diarrhea. Author(s): Park ES, Jo S, Seong JK, Nam TC, Yang IS, Choi MC, Yoon YS. Source: J Vet Sci. 2003 August; 4(2): 124-8. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=14610364&dopt=Abstract

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Effects of multiple deletions of murein hydrolases on viability, septum cleavage, and sensitivity to large toxic molecules in Escherichia coli. Author(s): Heidrich C, Ursinus A, Berger J, Schwarz H, Holtje JV. Source: Journal of Bacteriology. 2002 November; 184(22): 6093-9. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12399477&dopt=Abstract

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Electrorelease of Escherichia coli nucleoids. Author(s): Suleymanoglu E. Source: Folia Microbiol (Praha). 2002; 47(4): 365-70. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12422511&dopt=Abstract

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Enhanced inhibition of Escherichia coli O157:H7 by lysozyme and chelators. Author(s): Boland JS, Davidson PM, Weiss J. Source: J Food Prot. 2003 October; 66(10): 1783-9. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=14572214&dopt=Abstract

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Escherichia coli 6-pyruvoyltetrahydropterin synthase ortholog encoded by ygcM has a new catalytic activity for conversion of sepiapterin to 7,8-dihydropterin. Author(s): Woo HJ, Hwang YK, Kim YJ, Kang JY, Choi YK, Kim CG, Park YS. Source: Febs Letters. 2002 July 17; 523(1-3): 234-8. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12123838&dopt=Abstract

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Escherichia coli and its application in a mediated amperometric glucose sensor. Author(s): Ito Y, Yamazaki S, Kano K, Ikeda T. Source: Biosensors & Bioelectronics. 2002 December; 17(11-12): 993-8. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12392948&dopt=Abstract

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Evidence for Cu(I)-thiolate ligation and prediction of a putative copper-binding site in the Escherichia coli NADH dehydrogenase-2. Author(s): Rapisarda VA, Chehin RN, De Las Rivas J, Rodriguez-Montelongo L, Farias RN, Massa EM. Source: Archives of Biochemistry and Biophysics. 2002 September 1; 405(1): 87-94. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12176061&dopt=Abstract

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Expression and purification of a recombinant form of human aromatase from Escherichia coli. Author(s): Zhang F, Zhou D, Kao YC, Ye J, Chen S. Source: Biochemical Pharmacology. 2002 November 1; 64(9): 1317-24. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12392814&dopt=Abstract

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Fecal shedding of enterohemorrhagic Escherichia coli in weaned calves following treatment with probiotic Escherichia coli. Author(s): Tkalcic S, Zhao T, Harmon BG, Doyle MP, Brown CA, Zhao P.


Source: J Food Prot. 2003 July; 66(7): 1184-9. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12870751&dopt=Abstract •

G350 of Escherichia coli RNase P RNA contributes to Mg2+ binding near the active site of the enzyme. Author(s): Rasmussen TA, Nolan JM. Source: Gene. 2002 July 10; 294(1-2): 177-85. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12234679&dopt=Abstract

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Immune protection mediated by the probiotic Lactobacillus rhamnosus HN001 (DR20) against Escherichia coli O157:H7 infection in mice. Author(s): Shu Q, Gill HS. Source: Fems Immunology and Medical Microbiology. 2002 September 6; 34(1): 59-64. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12208607&dopt=Abstract

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Increased antibiotic resistance of E. coli exposed to static magnetic fields. Author(s): Stansell MJ, Winters WD, Doe RH, Dart BK. Source: Bioelectromagnetics. 2001 February; 22(2): 129-37. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11180259&dopt=Abstract

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Inhibition of adhesion of enterotoxigenic Escherichia coli K88 by soya bean tempe. Author(s): Kiers JL, Nout MJ, Rombouts FM, Nabuurs MJ, van der Meulen J. Source: Letters in Applied Microbiology. 2002; 35(4): 311-5. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12358694&dopt=Abstract

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Inhibitory effect of probiotic Escherichia coli strain Nissle 1917 on adhesion to and invasion of intestinal epithelial cells by adherent-invasive E. coli strains isolated from patients with Crohn's disease. Author(s): Boudeau J, Glasser AL, Julien S, Colombel JF, Darfeuille-Michaud A. Source: Alimentary Pharmacology & Therapeutics. 2003 July 1; 18(1): 45-56. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12848625&dopt=Abstract

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Insights into the reaction mechanism of Escherichia coli agmatinase by site-directed mutagenesis and molecular modelling. Author(s): Salas M, Rodriguez R, Lopez N, Uribe E, Lopez V, Carvajal N. Source: European Journal of Biochemistry / Febs. 2002 November; 269(22): 5522-6. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12423350&dopt=Abstract

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Isolation of Escherichia coli O157:H7 from foods in Greece. Author(s): Dontorou C, Papadopoulou C, Filioussis G, Economou V, Apostolou I, Zakkas G, Salamoura A, Kansouzidou A, Levidiotou S.

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Source: International Journal of Food Microbiology. 2003 May 15; 82(3): 273-9. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12593930&dopt=Abstract •

Oral administration of probiotic Escherichia coli after birth reduces frequency of allergies and repeated infections later in life (after 10 and 20 years). Author(s): Lodinova-Zadnikova R, Cukrowska B, Tlaskalova-Hogenova H. Source: International Archives of Allergy and Immunology. 2003 July; 131(3): 209-11. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12876412&dopt=Abstract

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Oxidative demethylation by Escherichia coli AlkB directly reverts DNA base damage. Author(s): Trewick SC, Henshaw TF, Hausinger RP, Lindahl T, Sedgwick B. Source: Nature. 2002 September 12; 419(6903): 174-8. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12226667&dopt=Abstract

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Pathogenicity of enterohemorrhagic Escherichia coli in neonatal calves and evaluation of fecal shedding by treatment with probiotic Escherichia coli. Author(s): Zhao T, Tkalcic S, Doyle MP, Harmon BG, Brown CA, Zhao P. Source: J Food Prot. 2003 June; 66(6): 924-30. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12800990&dopt=Abstract

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Prevalence of Escherichia coli O157:H7 and performance by beef feedlot cattle given Lactobacillus direct-fed microbials. Author(s): Brashears MM, Galyean ML, Loneragan GH, Mann JE, Killinger-Mann K. Source: J Food Prot. 2003 May; 66(5): 748-54. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12747680&dopt=Abstract

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Proteases in Escherichia coli and Staphylococcus aureus confer reduced susceptibility to lactoferricin B. Author(s): Ulvatne H, Haukland HH, Samuelsen O, Kramer M, Vorland LH. Source: The Journal of Antimicrobial Chemotherapy. 2002 October; 50(4): 461-7. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12356789&dopt=Abstract

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Quantification of microcystin-producing cyanobacteria and E. coli in water by 5'nuclease PCR. Author(s): Foulds IV, Granacki A, Xiao C, Krull UJ, Castle A, Horgen PA. Source: Journal of Applied Microbiology. 2002; 93(5): 825-34. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12392529&dopt=Abstract

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Role of dietary copper in enhancing resistance to Escherichia coli mastitis. Author(s): Scaletti RW, Trammell DS, Smith BA, Harmon RJ.


Source: Journal of Dairy Science. 2003 April; 86(4): 1240-9. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12741549&dopt=Abstract •

Role of internalization in the pathogenicity of Shiga toxin-producing Escherichia coli infection in a gnotobiotic murine model. Author(s): Aiba Y, Ishikawa H, Shimizu K, Noda S, Kitada Y, Sasaki M, Koga Y. Source: Microbiology and Immunology. 2002; 46(11): 723-31. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12516768&dopt=Abstract

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Role of lipopolysaccharides in the adhesion, retention, and transport of Escherichia coli JM109. Author(s): Abu-Lail NI, Camesano TA. Source: Environmental Science & Technology. 2003 May 15; 37(10): 2173-83. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12785523&dopt=Abstract

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Salt dependence of DNA binding by Thermus aquaticus and Escherichia coli DNA polymerases. Author(s): Datta K, LiCata VJ. Source: The Journal of Biological Chemistry. 2003 February 21; 278(8): 5694-701. Epub 2002 December 03. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12466277&dopt=Abstract

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Specific binding of ribosome recycling factor (RRF) with the Escherichia coli ribosomes by BIACORE. Author(s): Todorova RT, Saihara Y. Source: Molecular Biology Reports. 2003 June; 30(2): 113-9. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12841582&dopt=Abstract

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Susceptibility of antimicrobial-resistant urinary Escherichia coli isolates to fluoroquinolones and nitrofurantoin. Author(s): Karlowsky JA, Thornsberry C, Jones ME, Sahm DF. Source: Clinical Infectious Diseases : an Official Publication of the Infectious Diseases Society of America. 2003 January 15; 36(2): 183-7. Epub 2003 Jan 03. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12522750&dopt=Abstract

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The 5-enolpyruvylshikimate-3-phosphate synthase of glyphosate-tolerant soybean expressed in Escherichia coli shows no severe allergenicity. Author(s): Chang HS, Kim NH, Park MJ, Lim SK, Kim SC, Kim JY, Kim JA, Oh HY, Lee CH, Huh K, Jeong TC, Nam DH. Source: Molecules and Cells. 2003 February 28; 15(1): 20-6. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12661756&dopt=Abstract

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The comparison of aluminium effects and its uptake by Escherichia coli in different media. Author(s): Bojic A, Purenovic M, Kocic B, Mihailovic D, Bojic D. Source: Cent Eur J Public Health. 2002 June; 10(1-2): 66-71. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12096687&dopt=Abstract

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The effect of non-pathogenic Escherichia coli in symptomatic uncomplicated diverticular disease of the colon. Author(s): Fric P, Zavoral M. Source: European Journal of Gastroenterology & Hepatology. 2003 March; 15(3): 313-5. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12610327&dopt=Abstract

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The metal specificity and selectivity of ZntA from Escherichia coli using the acylphosphate intermediate. Author(s): Hou Z, Mitra B. Source: The Journal of Biological Chemistry. 2003 August 1; 278(31): 28455-61. Epub 2003 May 13. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12746428&dopt=Abstract

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The proteolytic activity of the recombinant cryptic human fibronectin type IV collagenase from E. coli expression. Author(s): Schnepel J, Tschesche H. Source: Journal of Protein Chemistry. 2000 November; 19(8): 685-92. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11307953&dopt=Abstract

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The Task Force on E. coli O157 Final Report: the view from here. Author(s): O'Brien SJ, Adak GK, Reilly WJ. Source: Commun Dis Public Health. 2001 September; 4(3): 154-6. No Abstract Available. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11732351&dopt=Abstract

Additional Web Resources A number of additional Web sites offer encyclopedic information covering CAM and related topics. The following is a representative sample: •

Alternative Medicine Foundation, Inc.: http://www.herbmed.org/

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Chinese Medicine: http://www.newcenturynutrition.com/

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drkoop.com: http://www.drkoop.com/InteractiveMedicine/IndexC.html

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Family Village: http://www.familyvillage.wisc.edu/med_altn.htm

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Google: http://directory.google.com/Top/Health/Alternative/

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Healthnotes: http://www.healthnotes.com/


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MedWebPlus: http://medwebplus.com/subject/Alternative_and_Complementary_Medicine

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Open Directory Project: http://dmoz.org/Health/Alternative/

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HealthGate: http://www.tnp.com/

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WebMDHealth: http://my.webmd.com/drugs_and_herbs

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WholeHealthMD.com: http://www.wholehealthmd.com/reflib/0,1529,00.html

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Yahoo.com: http://dir.yahoo.com/Health/Alternative_Medicine/

The following is a specific Web list relating to E. coli; please note that any particular subject below may indicate either a therapeutic use, or a contraindication (potential danger), and does not reflect an official recommendation: •

General Overview Bladder Infection Alternative names: Urinary Tract Infection [UTI] Source: Prima Communications, Inc.www.personalhealthzone.com Diarrhea Source: Healthnotes, Inc.; www.healthnotes.com Food Poisoning Source: Integrative Medicine Communications; www.drkoop.com Inflammatory Bowel Disease Source: Integrative Medicine Communications; www.drkoop.com Meningitis Source: Integrative Medicine Communications; www.drkoop.com Prostatitis Source: Healthnotes, Inc.; www.healthnotes.com Shock Source: Integrative Medicine Communications; www.drkoop.com Ulcerative Colitis Source: Healthnotes, Inc.; www.healthnotes.com Ulcerative Colitis Source: Integrative Medicine Communications; www.drkoop.com Urinary Tract Infection Source: Healthnotes, Inc.; www.healthnotes.com Urinary Tract Infection in Women Source: Integrative Medicine Communications; www.drkoop.com

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UTI Source: Integrative Medicine Communications; www.drkoop.com •

Herbs and Supplements Aesculus Alternative names: Horse Chestnut; Aesculus hippocastanum L. Source: Alternative Medicine Foundation, Inc.; www.amfoundation.org Arctostaphylos Alternative names: Bearberry; Arctostaphylos uva-ursi (L.) Spreng. Source: Alternative Medicine Foundation, Inc.; www.amfoundation.org Aristolochia Alternative names: Snakeroot, Guaco; Aristolochia sp Source: Alternative Medicine Foundation, Inc.; www.amfoundation.org Astragalus Sp Alternative names: Vetch, Rattlepod, Locoweed; Astragalus sp. Source: Alternative Medicine Foundation, Inc.; www.amfoundation.org Barberry Alternative names: Berberis vulgaris Source: Healthnotes, Inc.; www.healthnotes.com Berberis Alternative names: Barberry; Berberis sp. Source: Alternative Medicine Foundation, Inc.; www.amfoundation.org Borago Alternative names: Borage; Borago officinalis Source: Alternative Medicine Foundation, Inc.; www.amfoundation.org Bovine Colostrum Source: Healthnotes, Inc.; www.healthnotes.com Catechins Source: WholeHealthMD.com, LLC.; www.wholehealthmd.com Hyperlink: http://www.wholehealthmd.com/refshelf/substances_view/0,1525,1023,00.html Cranberry Alternative names: Vaccinium macrocarpon Source: Healthnotes, Inc.; www.healthnotes.com Cranberry Alternative names: Vaccinium macrocarpon Source: Integrative Medicine Communications; www.drkoop.com Cranberry Source: Prima Communications, Inc.www.personalhealthzone.com


Cranberry Source: WholeHealthMD.com, LLC.; www.wholehealthmd.com Hyperlink: http://www.wholehealthmd.com/refshelf/substances_view/0,1525,10019,00.html Crataegus Alternative names: Hawthorn; Crataegus oxyacantha L. Source: Alternative Medicine Foundation, Inc.; www.amfoundation.org Curcuma Alternative names: Turmeric; Curcuma longa L. Source: Alternative Medicine Foundation, Inc.; www.amfoundation.org Cynara Artichoke Alternative names: Artichoke; Cynara scolymus L. Source: Alternative Medicine Foundation, Inc.; www.amfoundation.org Doxycycline Source: Healthnotes, Inc.; www.healthnotes.com Eugenia Clove Alternative names: Cloves; Eugenia sp. Source: Alternative Medicine Foundation, Inc.; www.amfoundation.org Ginkgo Alternative names: Ginkgo biloba Source: Alternative Medicine Foundation, Inc.; www.amfoundation.org Goldenseal Alternative names: Hydrastis canadensis Source: Healthnotes, Inc.; www.healthnotes.com Goldenseal Alternative names: Hydrastis canadensis Source: Integrative Medicine Communications; www.drkoop.com Goldenseal Source: WholeHealthMD.com, LLC.; www.wholehealthmd.com Hyperlink: http://www.wholehealthmd.com/refshelf/substances_view/0,1525,791,00.html Hibiscus Alternative names: Hibiscus, Roselle; Hibiscus sp. Source: Alternative Medicine Foundation, Inc.; www.amfoundation.org Humulus Alternative names: Hops; Humulus lupulus L. Source: Alternative Medicine Foundation, Inc.; www.amfoundation.org Hydrastis Canadensis Source: Integrative Medicine Communications; www.drkoop.com

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Melaleuca Alternative names: Tea Tree Oil; Melaleuca alternifolia Source: Alternative Medicine Foundation, Inc.; www.amfoundation.org Momordica Alternative names: Bitter Gourd, Karela; Momordica charantia Linn. Source: Alternative Medicine Foundation, Inc.; www.amfoundation.org Musa Banana Alternative names: Plantain, Banana; Musa sp. Source: Alternative Medicine Foundation, Inc.; www.amfoundation.org Ocimum Alternative names: Basil, Albahaca; Ocimum basilicum Source: Alternative Medicine Foundation, Inc.; www.amfoundation.org Oregano/wild Marjoram Alternative names: Origanum vulgare Source: Healthnotes, Inc.; www.healthnotes.com Oregon Grape Alternative names: Berberis aquifolium Source: Healthnotes, Inc.; www.healthnotes.com Passiflora Alternative names: Passion Flower; Passiflora alata L. Source: Alternative Medicine Foundation, Inc.; www.amfoundation.org Phytolacca Alternative names: Poke root, Endod; Phytolacca dodecandra L. Source: Alternative Medicine Foundation, Inc.; www.amfoundation.org Piper Nigrum Alternative names: Black Pepper Source: Alternative Medicine Foundation, Inc.; www.amfoundation.org Pueraria Alternative names: Kudzu; Pueraria lobata Source: Alternative Medicine Foundation, Inc.; www.amfoundation.org Sambucus Alternative names: Black Elderberry; Sambucus nigra L. Source: Alternative Medicine Foundation, Inc.; www.amfoundation.org Smilax Alternative names: Sarsaparilla; Smilax glabra Roxb. Source: Alternative Medicine Foundation, Inc.; www.amfoundation.org Stevia Alternative names: Sweetleaf; Stevia rebaudiana Bertoni Source: Alternative Medicine Foundation, Inc.; www.amfoundation.org


Syzygium Clove Alternative names: Clove, Jamun; Syzygium sp. Source: Alternative Medicine Foundation, Inc.; www.amfoundation.org Tetracycline Source: Healthnotes, Inc.; www.healthnotes.com Thymus Alternative names: Thyme; Thymus vulgaris Source: Alternative Medicine Foundation, Inc.; www.amfoundation.org Vaccinium Macrocarpon Source: Integrative Medicine Communications; www.drkoop.com Vitex Alternative names: Chaste; Vitex agnus-castus Source: Alternative Medicine Foundation, Inc.; www.amfoundation.org

General References A good place to find general background information on CAM is the National Library of Medicine. It has prepared within the MEDLINEplus system an information topic page dedicated to complementary and alternative medicine. To access this page, go to the MEDLINEplus site at http://www.nlm.nih.gov/medlineplus/alternativemedicine.html. This Web site provides a general overview of various topics and can lead to a number of general sources.

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CHAPTER 4. DISSERTATIONS ON E. COLI Overview In this chapter, we will give you a bibliography on recent dissertations relating to E. coli. We will also provide you with information on how to use the Internet to stay current on dissertations. IMPORTANT NOTE: When following the search strategy described below, you may discover non-medical dissertations that use the generic term “E. coli” (or a synonym) in their titles. To accurately reflect the results that you might find while conducting research on E. coli, we have not necessarily excluded non-medical dissertations in this bibliography.

Dissertations on E. coli ProQuest Digital Dissertations, the largest archive of academic dissertations available, is located at the following Web address: http://wwwlib.umi.com/dissertations. From this archive, we have compiled the following list covering dissertations devoted to E. coli. You will see that the information provided includes the dissertation’s title, its author, and the institution with which the author is associated. The following covers recent dissertations found when using this search procedure: •

A Comparison of the Two Native Chea Proteins of the Bacterial Signaling System of Escherichia Coli by Kott, Laila; PhD from University of Massachusetts Amherst, 2002, 161 pages http://wwwlib.umi.com/dissertations/fullcit/3068575

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A Novel in Vivo Screening System for Protein Folding and Stability and Investigations on Variants of Dsba and Dsbc from Escherichia Coli by Philipps, Bjorn; Drscnat from Eidgenoessische Technische Hochschule Zuerich (switzerland), 2002, 140 pages http://wwwlib.umi.com/dissertations/fullcit/f377185

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A Reporter Bacteriophage - Beta-galactosidase Assay for Detection of Generic Escherichia Coli from Beef Carcasses by Goodridge, Lawrence David; PhD from University of Guelph (Canada), 2002, 196 pages http://wwwlib.umi.com/dissertations/fullcit/NQ67232

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A Study of the Interaction of E. coli Rna Polymerase and Bacteriophage S13 Dna by Rassart, Eric; PhD from Mcgill University (Canada), 1978 http://wwwlib.umi.com/dissertations/fullcit/NK39776

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Amino Acid Transport in Proline Auxotrophs of E. coli by Wilson, Onslow H; Advdeg from Mcgill University (Canada), 1966 http://wwwlib.umi.com/dissertations/fullcit/NK00282

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Analysis of Dna Repair and Genetic Recombination in the Bacterium Escherichia Coli: the Role of Single-strand Dna Exonucleases by Rajman, Luis A.; PhD from Brandeis University, 2002, 141 pages http://wwwlib.umi.com/dissertations/fullcit/3036430

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Assessing the Contributions of Dcm and Vsr to Spontaneous and Chemicallyinduced Dna Damage in Escherichia Coli by Pitsikas, Photini; PhD from Concordia University (Canada), 2002, 101 pages http://wwwlib.umi.com/dissertations/fullcit/NQ68193

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Atp Hydrolysis and Strand Exchange Reactions Promoted by Reca Protein from Escherichia Coli by Zhang, Zhaoqing; PhD from University of Delaware, 2002, 171 pages http://wwwlib.umi.com/dissertations/fullcit/3038347

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Biochemical and Structural Studies of Dna Strand Passage by Escherichia Coli Dna Topoisomerase I by Perry, Kay Huang; PhD from Northwestern University, 2002, 170 pages http://wwwlib.umi.com/dissertations/fullcit/3050574

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Biochemical Characterization of Drosophila Melanogaster Recq5 Dna Helicase and Studies of Escherichia coli Helicase IV by Ozsoy, Ayse Zeynep; PhD from The University of North Carolina at Chapel Hill, 2002, 144 pages http://wwwlib.umi.com/dissertations/fullcit/3061710

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Biochemical Characterization of Escherichia Coli-binding Proteins from Avian Air Sacs and Plasma by Weebadda, Wineeta K. C.; PhD from University of Guelph (Canada), 2002, 181 pages http://wwwlib.umi.com/dissertations/fullcit/NQ65840

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Characterization of a Novel Mechanism for Heat-labile Enterotoxin Secretion in Enterotoxigenic Escherichia Coli by Horstman, Amanda Lee; PhD from Duke University, 2002, 153 pages http://wwwlib.umi.com/dissertations/fullcit/3082802

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Characterization of Conserved Residues in the Putative Uridine Binding Domain of Escherichia Coli Pseudouridine 55 Synthase by Burnett, Ryan Stephen; PhD from Georgia Institute of Technology, 2002, 203 pages http://wwwlib.umi.com/dissertations/fullcit/3046877

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Characterization of Escherichia Coli Double-strand Uracil-dna Glycosylase and Analysis of Uracil-initiated Base Excision Dna Repair by Sung, Jung-suk; PhD from Oregon State University, 2003, 395 pages http://wwwlib.umi.com/dissertations/fullcit/3061921

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Characterization of Inositol Phosphatases from Escherichia Coli by Cottrill, Michael Alexander; Msc from University of Guelph (Canada), 2002, 138 pages http://wwwlib.umi.com/dissertations/fullcit/MQ65919

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Characterization of Nfsb, the Minor Oxygen-insensitive Nitroreductase of Escherichia Coli by Whiteway, Jacqueline Anne; PhD from Carleton University (Canada), 2002, 254 pages http://wwwlib.umi.com/dissertations/fullcit/NQ79446

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Characterization of the Fts Yex Operon of Escherichia Coli by Graham, Becky Jo; PhD from Iowa State University, 2002, 150 pages http://wwwlib.umi.com/dissertations/fullcit/3051466

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Characterizing Cspe Mutants of Escherichia Coli by Fernandes, Elaine Marie; Ms from Duquesne University, 2002, 80 pages http://wwwlib.umi.com/dissertations/fullcit/1409925

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Characterizing the N Terminus of the Escherichia Coli Dna Repair Protein Vsr Endonuclease by Monastiriakos, Stavroula K.; PhD from Concordia University (Canada), 2003, 136 pages http://wwwlib.umi.com/dissertations/fullcit/NQ77896

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Chemical Crosslinking of Ribonuclease P Holoenzyme from Escherichia Coli: Structure and Catalytic Mechanism of a Ribozyme by Sharkady, Stephen Michael; PhD from Tulane University, 2002, 161 pages http://wwwlib.umi.com/dissertations/fullcit/3046662

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Chromosomal Replication in Escherichia Coli: Mechanism of Lagging Strand Dna Synthesis by Leu, Frank Pou-fan; PhD from Cornell University Medical College, 2002, 205 pages http://wwwlib.umi.com/dissertations/fullcit/3057638

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Cloning, Purification and Characterization, and Biological Function of the Escherichia Coli Exoribonuclease Rnase R by Cheng, Zhuanfen; PhD from University of Miami, 2002, 136 pages http://wwwlib.umi.com/dissertations/fullcit/3071255

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Comparative Biochemistry and Genetic Analysis of Nucleoside Hydrolase in Escherichia Coli, Pseudomonas Aeruginosa, and Pseudomonas Fluorescens by Fields, Christopher John; PhD from University of North Texas, 2002, 139 pages http://wwwlib.umi.com/dissertations/fullcit/3076241

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Comparison and Analysis of Regulatory Dna Sequences' Activities in Two Bacterial Species: Escherichia Coli and Thermus Thermophilus Hb27 by Kwak, Jung-ho; PhD from Illinois Institute of Technology, 2002, 79 pages http://wwwlib.umi.com/dissertations/fullcit/3074348

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Conformational Variability in Adenylosuccinate Synthetase As Revealed by Crystal Structures of Mouse-muscle and Escherichia Coli Enzymes by Iancu, Cristina Valeria; PhD from Iowa State University, 2002, 108 pages http://wwwlib.umi.com/dissertations/fullcit/3061836

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Control of Chromosome and Plasmid Replication in Escherichia Coli by Olsson, Jan Anders; PhD from Uppsala Universitet (sweden), 2003, 65 pages http://wwwlib.umi.com/dissertations/fullcit/f27089

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Death of Escherichia Coli upon Exposure to Organic Acid by Wang, Jiyi (shirley); PhD from University of Missouri - Columbia, 2002, 153 pages http://wwwlib.umi.com/dissertations/fullcit/3052227

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Detection of Escherichia Coli O157: H7 and Related Species by Acoustic Wave Sensor by Deisingh, Anil Kenneth; PhD from University of Toronto (Canada), 2002, 171 pages http://wwwlib.umi.com/dissertations/fullcit/NQ69077

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Development of a Novel Escherichia Coli Assay for Rapid and Accurate Quantification of Lysine Bioavailability by Li, Xin; PhD from Texas A&m University, 2002, 181 pages http://wwwlib.umi.com/dissertations/fullcit/3072485

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Development of Traditional and Plant Virus-based Staphylococcus Aureus and Escherichia Coli Recombinant Enterotoxin Vaccines by Marshall, Matthew Joseph; PhD from University of Idaho, 2002, 222 pages http://wwwlib.umi.com/dissertations/fullcit/3076163

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Diagnostic Application of Monoclonal Antibodies to Surface Antigens of Enterohaemorrhagic and Enteropathogenic Escherichia Coli Strains by Kerr, Paul Gerard; PhD from Queen's University of Belfast (northern Ireland), 2002, 208 pages http://wwwlib.umi.com/dissertations/fullcit/f335889

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Dissecting the Inhibitory and Stimulatory Effects of Single-stranded Dna Binding Proteins on the Activities of Saccharomyces Cerevisiae Rad51 Protein and Escherichia Coli Reca Protein by Eggler, Aimee Laura; PhD from The University of Wisconsin Madison, 2002, 265 pages http://wwwlib.umi.com/dissertations/fullcit/3072786

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E. coli Lipase and Lysophospholipase by Nantel, Guy; PhD from University of Ottawa (Canada), 1977 http://wwwlib.umi.com/dissertations/fullcit/NK33712

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E. coli Mutants Defective in the Conversion of Pppgpp to Ppgpp by Somerville, Christopher R; PhD from University of Alberta (Canada), 1978 http://wwwlib.umi.com/dissertations/fullcit/NK40316

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Effect of a Mutator Gene on Mutagenesis and Evolutionary Success of E. coli in Continuous Culture by Nestmann, Earle R; PhD from York University (Canada), 1974 http://wwwlib.umi.com/dissertations/fullcit/NK21559

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Effect of Guanosine Tetraphosphate on Growth Rate and Stable Rna Synthesis in Escherichia Coli by Quintanilla, Heather Anne; Ms from The University of Texas - Pan American, 2002, 40 pages http://wwwlib.umi.com/dissertations/fullcit/1409779

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Effects of Activated Charcoal on Binding of Escherichia Coli O157:h7 and Salmonella Typhimurium in Sheep by Knutson, Haley Jo; Ms from Angelo State University, 2003, 25 pages http://wwwlib.umi.com/dissertations/fullcit/1413308

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Effects of Bovine Antibodies Directed against Ferric Citrate Receptor of Escherichia Coli, Feca, on Bacterial Iron Acquisition, Bacterial Growth, and Severity of Experimentally Induced Bovine Mastitis by Takemura, Kaori; PhD from The Ohio State University, 2002, 129 pages http://wwwlib.umi.com/dissertations/fullcit/3049121

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Effects of the Antimutagens Vanillin and Cinnamaldehyde on Spontaneous Mutation in Escherichia Coli Laci Strains and Salmonella Ta104 and on Global Gene Expression in Human Hepg2 Cells by Shaughnessy, Daniel Thomas; PhD from The University of North Carolina at Chapel Hill, 2002, 192 pages http://wwwlib.umi.com/dissertations/fullcit/3070912

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Electronic Sensor Array Incorporating Artificial Neural Network Algorithms for Rapid Identification and Quantification of Escherichia Coli and Salmonella Enterica Serovar Typhimurium and Their Volatile Metabolites by Siripatrawan, Ubonratana; PhD from Michigan State University, 2002, 159 pages http://wwwlib.umi.com/dissertations/fullcit/3053806

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Elucidation of the Regulatory Mechanisms That Govern the Transcription Cycle in Escherichia Coli by Bar-nahum, Gil; PhD from New York University, 2002, 151 pages http://wwwlib.umi.com/dissertations/fullcit/3062784

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Epidemiology of Escherichia Coli O157 in Range Cattle Production Environments by Renter, David Gregory; PhD from Kansas State University, 2002, 132 pages http://wwwlib.umi.com/dissertations/fullcit/3052600

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Escherichia Coli Exoribonuclease T: Structure, Function and Mechanism of Action by Zuo, Yuhong; PhD from University of Miami, 2002, 152 pages http://wwwlib.umi.com/dissertations/fullcit/3071259

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Escherichia Coli O157:h7: Growth in a Heterogeneous Food System and Biofilm Formation under Nutrient Limited Conditions by Prachaiyo, Preyatudsaney; PhD from University of Massachusetts Amherst, 2003, 111 pages http://wwwlib.umi.com/dissertations/fullcit/3078712

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Ethyl-nitrosourea-induced Mutagenesis in Escherichia Coli: Effects of Neighboring Base and Dna Methyltransferase by Cai, Zhehong; PhD from Southern Illinois University at Carbondale, 2002, 109 pages http://wwwlib.umi.com/dissertations/fullcit/3065341

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Examining the Modulation of Transcription Catalyzed by Escherichia Coli Rna Polymerase by Holmes, Shannon F.; PhD from The University of North Carolina at Chapel Hill, 2003, 178 pages http://wwwlib.umi.com/dissertations/fullcit/3086542

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Expanding the Genetic Code of Escherichia Coli by Wang, Lei; , PhD from University of California, Berkeley, 2002, 168 pages http://wwwlib.umi.com/dissertations/fullcit/3063589

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Exploration of Escherichia Coli As a Selection System for the Directed Evolution of House Fly (musca Domestica) Glutathione S-transferase-3 Specificity for Phosphotriester Substrates by Ericksen, Bryan Christian; PhD from University of California, Davis, 2002, 168 pages http://wwwlib.umi.com/dissertations/fullcit/3074562

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Expression and Characterization of the 33kda and 42kda Carboxyl-terminal Processing Fragment of Plasmodium Falciparum Merozoite Surface-protein-1 (msp1(33) and Msp-1(42)) in Escherichia Coli by Leung, Wai Hang; PhD from Chinese University of Hong Kong (people's Republic of China), 2003, 173 pages http://wwwlib.umi.com/dissertations/fullcit/3077692

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Expression of Bacterial Adhesins in Escherichia Coli: from Mapping of Adhesive Epitopes to Structure (yersinia Enterocolitica) by Tanskanen, Jarna Marika; PhD from Helsingin Yliopisto (finland), 2002, 47 pages http://wwwlib.umi.com/dissertations/fullcit/f336177

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Expression of Capsular Polysaccharide in Escherichia Coli K1: Studies of the Kps Export Complex by Prior, Kelli Ann; PhD from The University of Rochester, 2002, 151 pages http://wwwlib.umi.com/dissertations/fullcit/3064824

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Fate of Escherichia Coli O157:h7 and Listeria Monocytogenes on Fresh Produce during Sanitizer Exposure by Rodgers, Stephanie Lynn; PhD from Michigan State University, 2002, 183 pages http://wwwlib.umi.com/dissertations/fullcit/3053799

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Fluorescent Amplified Fragment Length Polymorphism Typing of Salmonella and Escherichia Coli O157 by Scott, Fiona Wendy; PhD from Open University (united Kingdom), 2002 http://wwwlib.umi.com/dissertations/fullcit/f754145

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Functional Analysis of Two Conserved Regions of Escherichia Coli Elongation Factor G As Studied by Site-directed Mutagenesis by Pereira, Ryan Apolinario; PhD from The Ohio State University, 2002, 124 pages http://wwwlib.umi.com/dissertations/fullcit/3081954

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Functional Insights Revealed by the Crystal Structures of Escherichia Coli Glucose-1phosphatase by Lee, Daniel Cho-en; Msc from Queen's University at Kingston (Canada), 2003, 103 pages http://wwwlib.umi.com/dissertations/fullcit/MQ74909

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Gene Expression a Study of the Regulation of Translation Initiation in E. coli by Pomeroy Cloney, Lynn Patricia; PhD from The University of New Brunswick (Canada), 1988 http://wwwlib.umi.com/dissertations/fullcit/NL43659

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Genetic Engineering of Two Escherichia Coli Strains Designed to Bioaccumulate Copper and Cadmium: Construction, Characterization, and Mutational Analysis of Key Regions Involved in High Affinity Metal Binding by Zagorski, Nicholas; PhD from Cornell University, 2003, 150 pages http://wwwlib.umi.com/dissertations/fullcit/3087000

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High-resolution Microarray Analysis of Rna Degradation in Escherichia Coli by Selinger, Douglas Wayne; PhD from Harvard University, 2003, 139 pages http://wwwlib.umi.com/dissertations/fullcit/3076913

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How Did the Substrate Cross the Membrane? Structural Studies of the Human Erythrocyte Anion Exchanger and the Escherichia Coli Glycerol-3-phosphate Transporter by Lemieux, Mary Joanne; PhD from New York University, 2003, 226 pages http://wwwlib.umi.com/dissertations/fullcit/3089406

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Identification and Characterization of a Secreted Protease from Escherichia Coli O157:h7 by Lathem, Wyndham Willoughby; PhD from The University of Wisconsin Madison, 2003, 205 pages http://wwwlib.umi.com/dissertations/fullcit/3089620

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Influence of the Chicken Major Histocompatibility Complex on the Development of Escherichia Coli Derived Cellulitis by Macklin, Kenneth Steven; PhD from Auburn University, 2003, 126 pages http://wwwlib.umi.com/dissertations/fullcit/3081589

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Interaction between Components of the Acrab-tolc, Acref-tolc and Acrd Multidrug Efflux Systems of Escherichia Coli by Huntley, Stuart Michael; PhD from Washington State University, 2002, 162 pages http://wwwlib.umi.com/dissertations/fullcit/3058785

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Interaction of Escherichia Coli Sigma Factors with Core Rna Polymerase by Anthony, Larry Cameron; PhD from The University of Wisconsin - Madison, 2003, 219 pages http://wwwlib.umi.com/dissertations/fullcit/3089639

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Interactions in the Folding Intermediate of Escherichia Coli Rnase H: Comparisons with the Native State Ensemble by Spudich, Giulietta Maria; PhD from University of California, Berkeley, 2002, 100 pages http://wwwlib.umi.com/dissertations/fullcit/3063563

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Maize As Production and Delivery Vehicle of Edible Vaccines against the Enterotoxigenic Escherichia Coli and the Swine Transmissible Gastroenteritis (tge) by Chikwamba, Rachel Kerina; PhD from Iowa State University, 2002, 209 pages http://wwwlib.umi.com/dissertations/fullcit/3061819

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Mapping the Interactions between Escherichia Coli Flavodoxin and Its Physiological Partners, Flavodoxin Reductase and Cobalamin-dependent Methionine Synthase by Hall, Diane Anita; PhD from University of Michigan, 2003, 134 pages http://wwwlib.umi.com/dissertations/fullcit/3079454

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Mast Cell Phagocytosis of Type 1 Fimbriated Escherichia Coli and Particulate Allergens by Novel Mechanisms by Shin, Jeoung-sook; PhD from Duke University, 2002, 120 pages http://wwwlib.umi.com/dissertations/fullcit/3063205

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Measurements of Fitness and Intra-specific Competition between Commensal Escherichia Coli and E. coli O157:h7 Strains by Durso, Lisa Marie; PhD from The University of Nebraska - Lincoln, 2003, 156 pages http://wwwlib.umi.com/dissertations/fullcit/3078607

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Mechanism of Detergent Resistance in Escherichia Coli and Related Bacteria by Rajagopal, Soumitra; PhD from The University of Nebraska - Lincoln, 2003, 84 pages http://wwwlib.umi.com/dissertations/fullcit/3085740

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Metabolic Engineering for Complex Natural Product Biosynthesis Utilizing Escherichia Coli by Pfeifer, Blaine Alan; PhD from Stanford University, 2002, 92 pages http://wwwlib.umi.com/dissertations/fullcit/3067916

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Methods to Study the Physical Locations of Lactic Acid Bacteria and Escherichia Coli O157:h7 in Fermented Sausages by Lee, Nancy Chunlan; Msc from University of Guelph (Canada), 2003, 166 pages http://wwwlib.umi.com/dissertations/fullcit/MQ76086

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Microbial Source Tracking Using F(+)rna Coliphage Typing and Escherichia Coli Antibiotic Resistance Assays by Stewart, Jill Rene; PhD from The University of North Carolina at Chapel Hill, 2003, 210 pages http://wwwlib.umi.com/dissertations/fullcit/3086628

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Molecular Analysis of Regulatory Elements Within the Escherichia Coli Fepb Leader Mrna by Hook-barnard, India Gail; PhD from University of Missouri - Columbia, 2003, 163 pages http://wwwlib.umi.com/dissertations/fullcit/3091932

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Molecular Cloning, Characterization and Expression in E. coli of a Cdna Encoding the Growth Hormone in Rainbow Trout (salmo Gairdneri) by Agellon, Luis Benn; PhD from Mcmaster University (Canada), 1987 http://wwwlib.umi.com/dissertations/fullcit/NL35904

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Molecular Epidemiologic Analysis of Uropathogenic Escherichia Coli Causing Urinary Tract Infections in Young, Healthy Women by Manges, Amee Rosenblum; PhD from University of California, Berkeley, 2002, 150 pages http://wwwlib.umi.com/dissertations/fullcit/3082306

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Molecular Epidemiologic Discovery of Uropathogenic Escherichia Coli Virulence and Transmission Factors by Bauer, Richard John; PhD from University of Michigan, 2003, 118 pages http://wwwlib.umi.com/dissertations/fullcit/3079409

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Molecular Epidemiology of Escherichia Coli O157:h7 in Cattle by Davis, Margaret Alison; PhD from Washington State University, 2002, 125 pages http://wwwlib.umi.com/dissertations/fullcit/3086296

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Mutational Analysis of a Conserved Region of the Synthetase Domain of Escherichia Coli Cytidine Triphosphate Synthetase by Iyengar, Akshai; Msc from Dalhousie University (Canada), 2002, 110 pages http://wwwlib.umi.com/dissertations/fullcit/MQ75485

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Negative Regulation of the Accbc Operon in Escherichia Coli by James, Ethan Siddhartha; PhD from University of Illinois at Urbana-champaign, 2003, 107 pages http://wwwlib.umi.com/dissertations/fullcit/3086089

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Nucleoside Phosphoramidites in the Automated, Solid Phase Synthesis of Oligoribonucleotides and Their Analogues the Chemical Synthesis of an E. coli Nformyl-methionine Trna by Usman, Nassim; PhD from Mcgill University (Canada), 1986 http://wwwlib.umi.com/dissertations/fullcit/NL38181

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On-farm Hazard Analysis and Critical Control Points for Dairy Market Cows and Diet Effects on Escherichia Coli O157 in Cattle by Vanbaale, Matthew Joe; PhD from Kansas State University, 2003, 164 pages http://wwwlib.umi.com/dissertations/fullcit/3090387

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Physiology of Escherichia Coli in Batch and Fed-batch Cultures with Special Emphasis on Amino Acid and Glucose Metabolism by Han, Ling; , PhD from Kungliga Tekniska Hogskolan (sweden), 2002, 140 pages http://wwwlib.umi.com/dissertations/fullcit/f409121

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Polar Clustering of the Methyl-accepting Chemotaxis Proteins in Escherichia Coli by Lybarger, Suzanne Renee; PhD from University of Michigan, 2002, 148 pages http://wwwlib.umi.com/dissertations/fullcit/3058007

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Post-translational Modification with Lipoic Acid in Escherichia Coli by Jordan, Sean Wesley; PhD from University of Illinois at Urbana-champaign, 2002, 96 pages http://wwwlib.umi.com/dissertations/fullcit/3044129

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Protein Dynamics: Studies of Adenylate Kinase Mutants from Escherichia Coli and Characterization of Adenylate Kinase Isoforms from Murine Cells. Applications of Fluorescence Spectroscopy and Microscopy by Ruan, Qiaoqiao; PhD from University of Illinois at Urbana-champaign, 2002, 176 pages http://wwwlib.umi.com/dissertations/fullcit/3070044

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Protein Targeting in Escherichia Coli by Schierle, Clark Friedrich; PhD from Harvard University, 2003, 135 pages http://wwwlib.umi.com/dissertations/fullcit/3091677

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Quantitative Detection of Escherichia Coli O157:h7 in Ground Beef by the Polymerase Chain Reaction Incorporating Immunomagnetic Separation by Guan, Jiewen; PhD from University of Massachusetts Amherst, 2002, 121 pages http://wwwlib.umi.com/dissertations/fullcit/3039361

Dissertations 185

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Regulation of Stx2f Synthesis in Escherichia Coli Strain H.i.8 by Holloway, Kimberly Anne; Msc from University of Guelph (Canada), 2002, 159 pages http://wwwlib.umi.com/dissertations/fullcit/MQ71788

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Role of Dna Geometry in Transcriptional Regulation by Ntrc at the Glnap2 Promoter in Escherichia Coli by Lilja, Anders Erik; PhD from University of Maryland College Park, 2002, 147 pages http://wwwlib.umi.com/dissertations/fullcit/3070561

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Role of Enteropathogenic Escherichia Coli and Turkey Coronavirus in Severe Intestinal Disease of Young Turkeys (poult Enteritis-mortality Syndrome) by Pakpinyo, Somsak; PhD from North Carolina State University, 2002, 116 pages http://wwwlib.umi.com/dissertations/fullcit/3059913

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Staphylococcus Leei: Metabolic Profile; Antimicrobial Susceptibility; Purification of Microbial Urease; Cloning, Sequencing and Expression of the Urease Gene in Escherichia Coli; Development of Elisa and Pcr Methods to Determine the Incidence of Infection by Jin, Ming; , PhD from City University of New York, 2002, 105 pages http://wwwlib.umi.com/dissertations/fullcit/3037406

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Starvation-induced Thermal Tolerance of Escherichia Coli O157:h7 by Zhang, Yi; , Msc from University of Guelph (Canada), 2002, 101 pages http://wwwlib.umi.com/dissertations/fullcit/MQ71217

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Structural and Biochemical Studies on Human 8-oxoguanine Dna Glycosylase, and Transcriptional Profiling of the Escherichia Coli Adaptive Response to Alkylation by Norman, Derek Paul Geoffrey; PhD from Harvard University, 2003, 121 pages http://wwwlib.umi.com/dissertations/fullcit/3091649

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Structural Investigation of the Capsular Antigens of Two E. coli Strains K26 and K49 by Beynon, Linda M; PhD from The University of British Columbia (Canada), 1988 http://wwwlib.umi.com/dissertations/fullcit/NL47258

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Structural Studies of the Chaperone Hsp31 from Escherichia Coli by Quigley, Paulene Mclean; PhD from University of Washington, 2003, 189 pages http://wwwlib.umi.com/dissertations/fullcit/3091057

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Structure and Function of Envz an Osmosensor in Escherichia Coli by Cai, Sheng Jian; PhD from Rutgers the State University of New Jersey - New Brunswick, 2002, 143 pages http://wwwlib.umi.com/dissertations/fullcit/3046720

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Structure and Function of Escherichia Coli Ribonuclease Iii by Su, Stephen V.; PhD from University of California, Los Angeles, 2002, 161 pages http://wwwlib.umi.com/dissertations/fullcit/3040227

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Structure and Function of the Escherichia Coli Rece Protein, a Member of the Recb Nuclease Domain Family by Chang, Hoshing Wan; PhD from University of Maryland College Park, 2002, 144 pages http://wwwlib.umi.com/dissertations/fullcit/3055555

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Structure-activity Studies of the Inhibition of Fabi, the Enoyl Acp Reductase from Escherichia Coli by Triclosan by Sivaraman, Sharada; PhD from State University of New York at Stony Brook, 2002, 148 pages http://wwwlib.umi.com/dissertations/fullcit/3078366

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Studies of Ubiquinone Synthesis in Escherichia Coli: the Regulation of Ubid and Ubix Genes by Zhang, Haitao; PhD from Loma Linda University, 2002, 87 pages http://wwwlib.umi.com/dissertations/fullcit/3046269

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Studies on the Low Molecular Weight Rna Bound to E. coli Ribosomes by Jacobs, Morley; PhD from The University of British Columbia (Canada), 1972 http://wwwlib.umi.com/dissertations/fullcit/NK11224

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Studies on the Subunit Structure and the Active Site Sequence of Succinyl Coenzyme a Synthetase from E. coli by Wang, Tusn-tien; PhD from University of Alberta (Canada), 1972 http://wwwlib.umi.com/dissertations/fullcit/NK13623

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Studies on the Succinate Oxidase System of E. coli by Kim, In-cheol; Advdeg from The University of British Columbia (Canada), 1971 http://wwwlib.umi.com/dissertations/fullcit/NK08311

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The Acute Inflammatory Response to E. coli in the Rabbit Quantitation and Kinetics by Kopaniak, Malgorzata M; PhD from University of Toronto (Canada), 1982 http://wwwlib.umi.com/dissertations/fullcit/NL07920

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The Antibacterial Immune Response to Escherichia Coli in the Flea Xenopsylla Cheopis by Driver, James David; PhD from University of Montana, 2002, 177 pages http://wwwlib.umi.com/dissertations/fullcit/3053333

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The Escherichia Coli Replication Factor Dnac Protein: Thermodynamics and Kinetics of Interactions with the Primary Replicative Helicase Dnab Protein and Nucleotide Cofactors by Galletto, Roberto; PhD from The University of Texas Graduate Sch. of Biomedical Sci. at Galveston, 2002, 342 pages http://wwwlib.umi.com/dissertations/fullcit/3077294

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The Function of Plasmid O157 on Escherichia Coli O157 Binding to Tissue Culture Cells by Han, Zhuolin; Msc from University of Alberta (Canada), 2002, 86 pages http://wwwlib.umi.com/dissertations/fullcit/MQ69713

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The Genetic Manipulation of Oxidative Stress in E. coli and A. Nidulans by Gruber, Margaret Yvonne; PhD from University of Waterloo (Canada), 1989 http://wwwlib.umi.com/dissertations/fullcit/NL49286

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The Genetics, Regulation and Biosynthesis of Group 1 Capsules in Escherichia Coli and Klebsiella Pneumoniae by Rahn, Andrea Rae; PhD from University of Guelph (Canada), 2002, 196 pages http://wwwlib.umi.com/dissertations/fullcit/NQ71750

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The Mechanism of Oxygen and Nitric Oxide Toxicity in Escherichia Coli by Woodmansee, Anh Nguyen; PhD from University of Illinois at Urbana-champaign, 2002, 122 pages http://wwwlib.umi.com/dissertations/fullcit/3070482

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The Recbcd Enzyme of Escherichia Coli: the Chi Effect by Jockovich, Maria-elena; PhD from University of Miami, 2002, 160 pages http://wwwlib.umi.com/dissertations/fullcit/3071285

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The Role of Metal Ions in the Structure and Function of Glucose Dehydrogenase in Escherichia Coli by James, Peter Lee; PhD from University of Southampton (united Kingdom), 2002 http://wwwlib.umi.com/dissertations/fullcit/f409313

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The Role of the Nusa Protein in Transcription Termination in E. coli by Peritz, Linda; PhD from University of Toronto (Canada), 1986 http://wwwlib.umi.com/dissertations/fullcit/NL29356

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The Role of Tyrosine Residues in Beta-galactosidase ( E. coli) Activity by Ring, Mark; PhD from University of Calgary (Canada), 1988 http://wwwlib.umi.com/dissertations/fullcit/NL46639

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Thermal Induction and Overexpression of a Foreign Protein in Escherichia Coli Culture by Razali, Firdausi; PhD from University of Waterloo (Canada), 2002, 228 pages http://wwwlib.umi.com/dissertations/fullcit/NQ70868

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Transcriptional Supercoiling of Intracellular Dna in Escherichia Coli and the Role of Dna Topoisomerase I by Stupina, Vera Aleksey; PhD from Harvard University, 2003, 181 pages http://wwwlib.umi.com/dissertations/fullcit/3091697

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Transient Kinetic Studies on the Mechanisms of Dna Binding, Dna Unwinding, and Dna-stimulated Atpase Activities by the Escherichia Coli Rep Helicase by Hsieh, Chang-tai John; PhD from Washington University, 2002, 306 pages http://wwwlib.umi.com/dissertations/fullcit/3065054

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Transitions between the Gut and the Gutter: a Global Examination of the Regulon Controlled by the Leucine-responsive Regulatory Protein (lrp) in Escherichia Coli by Tani, Travis Hiroshi; PhD from University of Michigan, 2002, 225 pages http://wwwlib.umi.com/dissertations/fullcit/3058061

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Use of 2d N.m.r. and Bacteriophages in Structural Studies of Some E. coli Antigens by Kuma-mintah, Agyeman; PhD from The University of British Columbia (Canada), 1989 http://wwwlib.umi.com/dissertations/fullcit/NL55953

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Use of Dna Fingerprinting and Novel Molecular Methods to Identify Sources of Escherichia Coli in the Environment by Scott, Troy Michael; PhD from University of Florida, 2002, 116 pages http://wwwlib.umi.com/dissertations/fullcit/3056781

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Use of Genetically Modified Carnobacterium Piscicola to Control Escherichia Coli O157:h7 in Vacuum-packaged Ground Beef by Watters, Douglas John; Msc from University of Alberta (Canada), 2002, 91 pages http://wwwlib.umi.com/dissertations/fullcit/MQ69774

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Vaccines against Escherichia Coli Respiratory Tract Infection in Broiler Chickens by Kariyawasam, Subhashinie; PhD from University of Guelph (Canada), 2003, 184 pages http://wwwlib.umi.com/dissertations/fullcit/NQ75984

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Whole-cell Immobilization and Biodetoxification of Organophosphate Nerve Agents by Genetically Engineered Escherichia Coli with Surface-expressed Cellulosebinding Domain and Organophophorus Hydrolase by Wang, Aijun Albert; PhD from University of California, Riverside, 2002, 114 pages http://wwwlib.umi.com/dissertations/fullcit/3042856

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X-ray Analysis of E. coli Hpr and Some Small Biological Molecules by El-kabbani, Ossama Ahmed Lotfi; PhD from The University of Saskatchewan (Canada), 1987 http://wwwlib.umi.com/dissertations/fullcit/NL35352

Keeping Current Ask the medical librarian at your library if it has full and unlimited access to the ProQuest Digital Dissertations database. From the library, you should be able to do more complete searches via http://wwwlib.umi.com/dissertations.

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CHAPTER 5. CLINICAL TRIALS AND E. COLI Overview In this chapter, we will show you how to keep informed of the latest clinical trials concerning E. coli.

Recent Trials on E. coli The following is a list of recent trials dedicated to E. coli.8 Further information on a trial is available at the Web site indicated. •

Phase III Randomized Study of SYNSORB Pk in Children with E. coli-Associated Hemolytic Uremic Syndrome Condition(s): Hemolytic Uremic Syndrome Study Status: This study is completed. Sponsor(s): National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK); Long Island Jewish Medical Center Purpose - Excerpt: Objectives: I. Determine the effect of SYNSORB Pk therapy on mortality and frequency of severe extrarenal complications observed in children with acute stage E. coli-associated hemolytic uremic syndrome. II. Determine the effect of SYNSORB Pk therapy on the need for the duration of dialysis in these patients. III. Determine the effect of SYNSORB Pk therapy on the recovery of renal function and resolution of urinary abnormalities in these patients. Phase(s): Phase III Study Type: Interventional Contact(s): see Web site below Web Site: http://clinicaltrials.gov/ct/show/NCT00004465

8

These are listed at www.ClinicalTrials.gov.

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Keeping Current on Clinical Trials The U.S. National Institutes of Health, through the National Library of Medicine, has developed ClinicalTrials.gov to provide current information about clinical research across the broadest number of diseases and conditions. The site was launched in February 2000 and currently contains approximately 5,700 clinical studies in over 59,000 locations worldwide, with most studies being conducted in the United States. ClinicalTrials.gov receives about 2 million hits per month and hosts approximately 5,400 visitors daily. To access this database, simply go to the Web site at http://www.clinicaltrials.gov/ and search by “E. coli” (or synonyms). While ClinicalTrials.gov is the most comprehensive listing of NIH-supported clinical trials available, not all trials are in the database. The database is updated regularly, so clinical trials are continually being added. The following is a list of specialty databases affiliated with the National Institutes of Health that offer additional information on trials: •

For clinical studies at the Warren Grant Magnuson Clinical Center located in Bethesda, Maryland, visit their Web site: http://clinicalstudies.info.nih.gov/

•

For clinical studies conducted at the Bayview Campus in Baltimore, Maryland, visit their Web site: http://www.jhbmc.jhu.edu/studies/index.html

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For cancer trials, visit the National Cancer Institute: http://cancertrials.nci.nih.gov/

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For eye-related trials, visit and search the Web page of the National Eye Institute: http://www.nei.nih.gov/neitrials/index.htm

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For heart, lung and blood trials, visit the Web page of the National Heart, Lung and Blood Institute: http://www.nhlbi.nih.gov/studies/index.htm

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For trials on aging, visit and search the Web site of the National Institute on Aging: http://www.grc.nia.nih.gov/studies/index.htm

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For rare diseases, visit and search the Web site sponsored by the Office of Rare Diseases: http://ord.aspensys.com/asp/resources/rsch_trials.asp

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For alcoholism, visit the National Institute on Alcohol Abuse and Alcoholism: http://www.niaaa.nih.gov/intramural/Web_dicbr_hp/particip.htm

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For trials on infectious, immune, and allergic diseases, visit the site of the National Institute of Allergy and Infectious Diseases: http://www.niaid.nih.gov/clintrials/

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For trials on arthritis, musculoskeletal and skin diseases, visit newly revised site of the National Institute of Arthritis and Musculoskeletal and Skin Diseases of the National Institutes of Health: http://www.niams.nih.gov/hi/studies/index.htm

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For hearing-related trials, visit the National Institute on Deafness and Other Communication Disorders: http://www.nidcd.nih.gov/health/clinical/index.htm

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For trials on diseases of the digestive system and kidneys, and diabetes, visit the National Institute of Diabetes and Digestive and Kidney Diseases: http://www.niddk.nih.gov/patient/patient.htm

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For drug abuse trials, visit and search the Web site sponsored by the National Institute on Drug Abuse: http://www.nida.nih.gov/CTN/Index.htm

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•

For trials on mental disorders, visit and search the Web site of the National Institute of Mental Health: http://www.nimh.nih.gov/studies/index.cfm

•

For trials on neurological disorders and stroke, visit and search the Web site sponsored by the National Institute of Neurological Disorders and Stroke of the NIH: http://www.ninds.nih.gov/funding/funding_opportunities.htm#Clinical_Trials

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CHAPTER 6. PATENTS ON E. COLI Overview Patents can be physical innovations (e.g. chemicals, pharmaceuticals, medical equipment) or processes (e.g. treatments or diagnostic procedures). The United States Patent and Trademark Office defines a patent as a grant of a property right to the inventor, issued by the Patent and Trademark Office.9 Patents, therefore, are intellectual property. For the United States, the term of a new patent is 20 years from the date when the patent application was filed. If the inventor wishes to receive economic benefits, it is likely that the invention will become commercially available within 20 years of the initial filing. It is important to understand, therefore, that an inventor’s patent does not indicate that a product or service is or will be commercially available. The patent implies only that the inventor has “the right to exclude others from making, using, offering for sale, or selling” the invention in the United States. While this relates to U.S. patents, similar rules govern foreign patents. In this chapter, we show you how to locate information on patents and their inventors. If you find a patent that is particularly interesting to you, contact the inventor or the assignee for further information. IMPORTANT NOTE: When following the search strategy described below, you may discover non-medical patents that use the generic term “E. coli” (or a synonym) in their titles. To accurately reflect the results that you might find while conducting research on E. coli, we have not necessarily excluded non-medical patents in this bibliography.

Patents on E. coli By performing a patent search focusing on E. coli, you can obtain information such as the title of the invention, the names of the inventor(s), the assignee(s) or the company that owns or controls the patent, a short abstract that summarizes the patent, and a few excerpts from the description of the patent. The abstract of a patent tends to be more technical in nature, while the description is often written for the public. Full patent descriptions contain much more information than is presented here (e.g. claims, references, figures, diagrams, etc.). We

9Adapted

from the United States Patent and Trademark Office: http://www.uspto.gov/web/offices/pac/doc/general/whatis.htm.

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will tell you how to obtain this information later in the chapter. The following is an example of the type of information that you can expect to obtain from a patent search on E. coli: •

Antibiotics GE 23077, pharmaceutically acceptable salts and compositions, and use thereof Inventor(s): Ciciliato; Ismaela (Busto Arsizio, IT), Corti; Emiliana (Rovellasca, IT), Kurz; Michael (Hofheim, DE), Marinelli; Flavia (Milan, IT), Montanini; Nicoletta (Malnate, IT), Sarubbi; Edoardo Giacomo (Fontenay-Sous-Bois, FR), Selva; Enrico (Gropello Cairoli, IT), Stefanelli; Stefania (Legnano, IT) Assignee(s): Biosearch Italia S.p.A. (Milan, IT) Patent Number: 6,586,393 Date filed: November 9, 2001 Abstract: The invention relates to an antibiotic substance of microbial origin, arbitrarily denominated GE23077 complex and the individual factors which constitute it, a mixture of said factors in any proportion, the pharmaceutically acceptable salts and compositions thereof, and their use as an antibacterial agent having a selective inhibitory activity against E. coli RNA polymerase. Excerpt(s): The present invention concerns an antibiotic substance of microbial origin, arbitrarily denominated GE23077 complex and the individual factors that constitute it, namely GE23077 factor A1, GE23077 factor A2, GE23077 factor B1 and GE23077 factor B2, a mixture of said factors in any proportion, the pharmaceutically acceptable salts and compositions thereof, and their use as an antibacterial agent with a selective inhibitory activity against E. coli RNA polymerase. Another object of the present invention is a process for preparing GE23077 complex, namely GE23077 factor A1, GE23077 factor A2, GE23077 factor B1 and GE23077 factor B2, a mixture of said factors in any proportion, hereinafter reported as GE23077 compounds. Actinomadura sp. DSMZ 13491 was isolated from a soil sample and deposited on May 22, 2000, with the DSMZ, (Deutsche Sammlung von Mikroorganismen und Zellkulturen GmbH, Mascheroder Weg 1b, D-38124 Braunschweig, Germany), under the provision of the Budapest Treaty. The strain was accorded accession number DSMZ 13491. Web site: http://www.delphion.com/details?pn=US06586393__

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Antibodies to intimin-like proteins of E. coli Inventor(s): Dougan; Gordon (London, GB), Frankel; Gad (London, GB) Assignee(s): Imperial College of Science, Technology & Medicine (London, GB) Patent Number: 6,623,737 Date filed: April 2, 1998 Abstract: The invention is related to antibodies, particularly monoclonal antibodies, which recognize particularly epitopes of the intimin protein of enteropathogenic E. coli and enterohemorrhagic E. coli, methods of detecting such E. coli by use of these antibodies, and kits containing these antibodies for diagnosis. Excerpt(s): The present invention relates to antibodies, particularly monoclonal antibodies which recognise particular epitopes of the intimin protein of enteropathogenic E. coli and enterohemorrhagic E. coli, their use in the detection of

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such enterophathogenic E. coli, and kits containing such antibody for such use. Enteropathogenic Escherichia coli (EPEC) were the first E. coli linked with diarrhoea in humans. They are a sub-group of pathogenic E. coli that are a major cause of infant diarrhoea. Enterohemorrhagic E. coli (EHEC) are another such sub-group. EPEC normally fall into several distinct serotype groups based on the type of lipopolysaccharide which is expressed at their cell surface. The most common serogroups that are associated with EPEC are O26, O55, O111, O114, O126, O127, O128, O142 and O157. Although EPEC and EHEC infections are still a serious problem worldwide, no specific treatment or vaccine is as yet available for treating these diseases and furthermore, no relatively simply and/or accurate tests are as yet available for diagnosis. One major problem in diagnosing EPEC infections is that, apart from the link with several O serotypes, EPEC are difficult to distinguish from commensal, nonpathogenic E. coli which are usually resident in the intestines of healthy individuals. Ultra-structural studies of intestinal biopsy specimens from children with EPECinduced diarrhoea have shown that EPEC attach to the intestinal epithelium in a characteristic fashion, which is central to the pathogenesis of the disease. Web site: http://www.delphion.com/details?pn=US06623737__ •

Cold-shock regulatory elements, constructs thereof, and methods of use Inventor(s): Inouye; Masayori (Piscataway, NJ), Wang; Nan (Piscataway, NJ), Yamanaka; Kunitoshi (Highland Park, NJ) Assignee(s): University of Medicine and Dentistry of New Jersey (NJ) Patent Number: 6,610,533 Date filed: March 1, 2000 Abstract: A fourth cold shock protein of the Escherichia coli CspA family is disclosed, as are the regulatory elements of the 5' UTR of the corresponding gene. The cspI gene is located at 35.2 min on the E. coli chromosome map, and CspI shows 70, 70, and 79% identity of CspA, CspB, and CspG, respectively. The 5'-untranslated region of the cspI mRNA consists of 145 bases and causes a negative effect on cspI expression at 37.degree. C. The cspI mRNA was very unstable at 37.degree. C. but was stabilized upon cold shock. The 5' UTR of cspI can enhance the translation of cold shock inducible genes under conditions that elicit a cold shock response in bacteria. Excerpt(s): The invention relates to the control of bacterial gene expression, especially the regulation of bacterial gene expression under conditions of physiologic stress. More specifically, the invention relates to the regulation of bacterial gene expression under conditions of physiologic stress that induce the cold shock response of a bacterium. The regulation of bacterial gene expression occurs at many levels, including transcriptional control, or control of the synthesis of mRNA from a given gene; translational control, or the regulation of the efficiency by which the mRNA is translated into polypeptide sequence by the ribosome; and mRNA stability, or the efficiency at which a given mRNA population within the cell is degraded and rendered inactive. The control of bacterial gene expression under conditions of physiologic stress that elicit the cold shock response of the bacterium involve regulation at all three of the levels described above. The response of bacteria to physiologic stress involve the tightly controlled expression of a small number of genes that function to allow the cell to adapt to and multiply under stress conditions. For example, when bacterial cells are exposed to temperatures above the normal physiologic temperature for that organism, a set of genes, designated the heat shock genes, are expressed. This response to elevated temperatures is well known

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and described in the prior art. Conversely, when bacterial cells are exposed to lower than physiologic temperatures, a different set of genes, designated as cold shock (Cs) genes, are expressed. Expression of the cs genes allow the cell to first adapt to the physiologic stress, and subsequently grow under conditions of physiologic stress. This invention relates to the specific processes that regulate the expression of cs genes. Web site: http://www.delphion.com/details?pn=US06610533__ •

Combined ligand and receptor display Inventor(s): Borrebaeck; Carl (Hjarup, SE), Malmborg; Anki (Lund, SE), Soderlind; Eskil (Lund, SE) Assignee(s): Bioinvent International, AB (Lund, SE) Patent Number: 6,607,881 Date filed: June 30, 1998 Abstract: A method for selecting nucleic acid sequences encoding ligand and receptor molecules capable of specific binding to each other is disclosed in which nucleic acid encoding ligand or receptor molecules is expressed in a host microorganism in combination with a surface molecule, such as E. coli pili, so that the ligand or receptor are displayed on the surface of the host microorganism. A replicable genetic unit, such as a filamentous bacteriophage, is used to display candidate binding partners to the ligand or receptor, with the binding of the ligand or receptor to the candidate binding partner mediating the transfer of nucleic acid from the replicable genetic unit to the microorganism. The method can be highly selective as the host microorganism is modified so that it does not display the surface molecule other than as a fusion with the ligand or receptor molecule. The method is rapid and simple and opens up new applications based on the detection of ligand and receptors where both are unknown. Excerpt(s): The present invention relates to methods for selecting specific ligand and receptor encoding sequences and to kits for carrying out the methods. There is a continuing need for highly efficient selection systems in the screening of protein libraries, such as antibody libraries. Current systems are based on the display of antibodies on the surface of microorganisms containing the gene of the antibody. Specific clones can then be selected with immobilized antigens, for instance by panning on microtiter plates (Parmley and Smith, 1988, Gene, 73, 305-318 and Barbas III et al, 1991, PNAS 88, 7978-7982), selection on magnetic beads (Hawkins et al, 1992, J. Mol. Biol. 226, 889-896), immunotubes (Marks et al, 1991, J. Mol. Biol, 222, 581-597), affinity chromatography (McCafferty et al, 1990, Nature, 348, 552-554), fluorescence assisted cell sorter (FACS), antigen specific precipitation (Kang et al, 1991, PNAS, 88, 4363-4366) and SAP (Duenas and Borrebaeck, 1994, Bio/Technology 12, 999-1002). Several antibody libraries have been constructed on the surface of phages, e.g. a bacteriophage such as fd (McCafferty et al, 1990, Nature, 348, 552-554) or M13 (Barbas III et al, 1991, PNAS, 88, 7978-7982). The possibility of expressing antibodies (scFv) on the surface of bacteria has also been demonstrated by fusions to bacterial membrane proteins like Lpp-Omp A (Francisco et al, 1993, PNAS, 90, 10444-10448) and PAL (Fuchs et al, 1991, Bio/Technology, 9, 1369-1372). For a recent review of antibody display systems and the screening of antibody libraries, see Little, 1994, Biotech. Adv., 12, 539-555. Web site: http://www.delphion.com/details?pn=US06607881__

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Compositions and methods for Taxol biosynthesis Inventor(s): Croteau; Rodney B. (Pullman, WA), Wildung; Mark R. (Colfax, WA) Assignee(s): Washington State University Research Foundation (Pullman, WA) Patent Number: 6,610,527 Date filed: June 13, 2000 Abstract: The taxadiene synthase gene of Pacific yew has been cloned and its nucleic acid and polypeptide sequence is presented. Truncation or removal of the transit peptide increases expression of the cloned taxadiene synthase gene expression in E. coli cells. Excerpt(s): This invention is related to the field of detection of diterpenoid biosynthesis, particularly to the biosynthesis of taxoid compounds such as Taxol. The supply of TAXOL.RTM. (paclitaxel) from the original source, the bark of the Pacific yew (Taxus brevifolia Nutt.; Taxaceae) is limited. As a result, there have been intensive efforts to develop alternate means of production, including isolation from the foliage and other renewable tissues of plantation-grown Taxus species, biosynthesis in tissue culture systems, and semisynthesis of TAXOL.RTM. (paclitaxel) and its analogs from advanced taxane diterpenoid (taxoid) metabolites that are more readily available (Cragg et al., J Nat. Prod. 56:1657-1668, 1993). Total synthesis of TAXOL.RTM. (paclitaxel), at present, is not commercially viable (Borman, Chem. Eng. News 72(7):32-34, 1994), and it is clear that in the foreseeable future the supply of TAXOL.RTM. (paclitaxel) and its synthetically useful progenitors must rely on biological methods of production, either in Taxus plants or in cell cultures derived therefrom (Sufffiess, in Taxane Anticancer Agents: Basic Science and Current Status, Georg et al., eds., American Chemical Society, Washington, D.C., 1995, pp. 1-17). Taxa-4(5),11(12)-diene synthase ("taxadiene synthase"), the enzyme responsible for the initial cyclization of geranylgeranyl diphosphate, to delineate the taxane skeleton, has been isolated from T. brevifolia stem tissue, partially purified, and characterized (Hezari et al., Arch. Biochem. Biophys. 322:437-444, 1995). Web site: http://www.delphion.com/details?pn=US06610527__

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Cytoplasmic expression of antibodies, antibody fragments and antibody fragment fusion proteins in E. coli Inventor(s): Bosslet; Klaus (Marburg, DE), Czech; Joerg (Marburg, DE), Opper; Martin (Marburg, DE) Assignee(s): Aventis Pharma Deutschland GmbH (Frankfurt am Main, DE) Patent Number: 6,602,688 Date filed: March 22, 1999 Abstract: The invention relates to the cytoplasmic expression of antibodies, antibody fragments and antibody fragment fusion molecules in E. coli. In particular, antibody fragment fusion molecules having an antibody moiety which is directed against tumors and an enzyme moiety which cleaves a nontoxic prodrug to give the toxic drug can be advantageously prepared in this way while retaining their respective functional properties. Excerpt(s): The expression of functional antibodies and antibody fragments in E. coli is known in the prior art, but these methods require the use of signal sequences which

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direct polypeptide transport into the periplasm. When expression takes place in the E. coli periplasm, the expression yields are in the range of a few.mu.g per liter of culture medium (Ayala et al., Bio Techniques 13, pp. 790-799, 1992). In addition, refolding experiments are often required in order to obtain functionally active antibody fragments (such as Fab) or antigen-binding regions (such as a single chain Fv(sFv)). There is a need therefore, to develop improved methods for expressing functionally active antibodies and antibody fragments. The prior art does not teach recombinant production of antibodies or antibody fragments which can be isolated from the cytoplasm in functional form. Such molecules would be useful in the production of therapeutic agents. Bagshawe describes a method for generating cytotoxic agents that are directed towards cancer sites, termed Antibody Directed Enzyme Prodrug Therapy (ADEPT). Bagshawe, Br. J. Cancer, vol. 60, pp. 275-281, 1989. Using ADEPT, an antibody or antibody fragment that specifically binds to a cancer cell is fused to an enzyme that is capable of converting a non-toxic drug into a toxic drug. Only those cells to which the fusion protein is bound will be killed upon administration of the precursor of the toxic drug. The.beta.-glucuronidase of Escherichia coli has been well characterized biochemically and genetically. The gene (uid A) has been cloned by Jefferson et al. (PNAS vol. 83, pp. 8447-8451, 1986) and employed as a reporter gene for heterologous control regions. Web site: http://www.delphion.com/details?pn=US06602688__ •

Deregulation of glutamine PRPP amidotransferase activity Inventor(s): Smith; Janet L. (Lafayette, IN), Switzer; Robert L. (Urbana, IL), Zalkin; Howard (West Lafayette, IN) Assignee(s): Purdue Research Foundation (West Lafayette, IA), The Board of Trustees of the University of Illinois (Urbana, IL) Patent Number: 6,586,216 Date filed: March 13, 2001 Abstract: The present invention is directed to a modified amidotransferase. The amino acid sequence of the modified amidotransferase differs from the amino acid sequence of a native E. coli glutamine PRPP amidotransferase in that one or more amino acid residues of the modified amidotransferase are substituted at positions equivalent to amino acid positions in Bacillus amidotransferase selected from the group consisting of 282, 283, 307, and 347 of SEQ ID NO:1, wherein the modified amidotransferase is less sensitive to end-product inhibition than is the native E. coli glutamine PRPP amidotransferase. Excerpt(s): This invention relates to the deregulation of purine nucleotide biosynthesis. More particularly, this invention is directed to the modification of glutamine phosphoribosylpyrophosphate (PRPP) amidotransferase to decrease end-product inhibition of glutamine PRPP amidotransferase activity. Glutamine PRPP amidotransferase catalyzes the initial reaction in de novo purine nucleotide synthesis and is the key regulatory enzyme in the pathway. Genes encoding glutamine PRPP amidotransferase have been cloned from more than 20 organisms including bacteria, eukarya, and archea. In particular, the enzymes from Escherichia coli and Bacillus subtilis have been purified to homogeneity and are well-characterized, including having the X-ray structures determined for these enzyme species. The E. coli and B. subtilis enzymes are both homotetramers and are representative of two classes of glutamine PRPP amidotransferases. Enzymes of the B. subtilis class are synthesized with an

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NH.sub.2 terminal propeptide and an Fe--S center, whereas enzymes of the E. coli class have neither. Purine nucleotide biosynthesis is regulated, at both the gene (transcription/translation) and the protein (enzymatic activity) level. Attempts at increasing the biosynthesis of purine nucleotides have focused on the deregulation of genes encoding pathway enzymes. However, the enzymatic activity of a key pathway enzyme, glutamine PRPP amidotransferase, is inhibited by the pathway end-products, adenine and guanine nucleotides. Therefore an effective strategy for enhancing host cell production of purine nucleotides includes the use of a modified glutamine PRPP amidotransferase, wherein the modification reduces the sensitivity of the enzyme to end-product inhibition by adenine and guanine nucleotides. Web site: http://www.delphion.com/details?pn=US06586216__ •

Desaturase antigen of mycobacterium tuberculosis Inventor(s): Gicquel; Brigitte (Paris, FR), Jackson; Mary (Paris, FR) Assignee(s): Institut Pasteur (Paris, FR) Patent Number: 6,582,925 Date filed: April 20, 1999 Abstract: The use of genetic methodology based on the fusion of the proteins with the alcaline phosphatase (Lim et al., 1995) has allowed the isolation of a new exported protein of M. tuberculosis. In the present article, first of all the isolation of a gene encoding this exported protein called DES is described as well as its characterization and its distribution among the different mycobacterial species. It is notably shown that the protein has in its primary sequence amino acids only found at the level of active sites of enzymes of class II diiron-oxo proteins family. Among the proteins of this family, DES protein of M. tuberculosis does not present significative homologies with stearoyl ACP desaturases. Secondly, the antigenic feature of this protein has been studied. For this, DES protein of M. tuberculosis has been overexpressed in E. coli under recombinant and purified protein form from this bacterium. The reactivity of tuberculous patients sera infected by M. tuberculosis or M. bovis against DES protein in Western blot experimentations has been tested. 100% of the tested patients did recognize the protein. The intensity of the antibody response against DES protein measured by ELISA of tuberculous patients sera compared with the one relating to sera patients suffering from other pathologies show that there is a significative difference between the intensity of the antibody responses of these two categories of patients. Accordingly, DES protein is a potentially interesting tool for the tuberculosis serodiagnostic. Excerpt(s): Tuberculosis and leprosy, caused by the bacilli from the Mycobacterium tuberculosis complex and M. leprae respectively are the two major mycobacterial diseases. Pathogenic mycobacteria have the ability to survive within host phagocytic cells. From the interactions between the host and the bacteria results the pathology of the tuberculosis Infection through the damages the host immune response causes on tissues (Andersen & Brennan, 1994). Alternatively, the protection of the host is also dependent on its interactions with mycobacteria. Identification of the bacterial antigens involved in these interactions with the immune system is essential for the understanding of the pathogenic mechanisms of mycobacteria and the host immunological response in relation to the evolution of the disease. It is also of great importance for the improvement of the strategies for mycobacterial disease control through vaccination and immunodiagnosis. Through the years, various strategies have been followed for identifying mycobacterial antigens. Biochemical tools for fractionating

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and analysing bacterial proteins permitted the isolation of antigenic proteins selected on their capacity to elicit B or T cell responses (Romain et al., 1993; Sorensen et al., 1995). The recent development of molecular genetic methods for mycobacteria (Jacobs et al., 1991; Snapper et al., 1990; Hatful, 1993. Young et al., 1985) allowed the construction of DNA expression libraries of both M. tuberculosis and M. leprae in the.lambda.gt11vector and their expression in E. coli. The screening of these recombinant libraries using murine polyclonal or monoclonal antibodies and patient sera led to the identification of numerous antigens (Braibant et al., 1994; Hermans et al., 1995; Thole & van der Zee, 1990). However, most of them turned out to belong to the group of highly conserved heat shock proteins (Thole & van der Zee 1990; Young et al., 1990). Web site: http://www.delphion.com/details?pn=US06582925__ •

Expression of lipoproteins Inventor(s): Becker; Robert S. (Henryville, PA), Erdile; Lorne F. (Stroudsburg, PA), Gray; Maryann B. (Bartonsville, PA), Huebner; Robert C. (Stroudsburg, PA), Pyle; Derek J. (East Stroudsburg, PA), Warakomski, Jr.; Donald J. (Tannersville, PA) Assignee(s): Connaught Laboratories, Inc. (Swiftwater, PA) Patent Number: 6,538,118 Date filed: April 28, 1998 Abstract: Heterologous lipidated proteins formed recombinantly are disclosed and claimed. The expression system can be E. coli. The heterologous lipidated protein has a leader sequence which does not naturally occur with the protein portion of the lipidated protein. The lipidated protein can have the Borrelia OspA leader sequence. The protein portion can be OspC, PspA, UreA, Ure B, or a fragment thereof. Methods and compositions for forming and employing the proteins are also disclosed and claimed. Excerpt(s): The present invention is concerned with genetic engineering to effect expression of lipoproteins from vectors containing nucleic acid molecules encoding the lipoproteins. More particularly, the present invention relates to expression of a recombinant lipoprotein wherein the lipidation thereof is from expression of a first nucleic acid sequence and the protein thereof is from expression of a second nucleic acid sequence, the first and second nucleic acid sequences, which do not naturally occur together, being contiguous. The invention further relates to expression of such lipoproteins wherein the first nucleic acid sequence encodes a Borrelia lipoprotein leader sequence. The invention also relates to recombinant lipidated proteins expressed using the nucleic acid sequence encoding the OspA leader sequence, methods of making and using the same compositions thereof and methods of using the compositions. The invention additionally relates to nucleic acid sequences encoding the recombinant lipoproteins, vectors containing and/or expressing the sequences, methods for expressing the lipoproteins and methods for making the nucleic acid sequences and vectors; compositions employing the lipoproteins, including immunogenic or vaccine compositions, such compositions preferably having improved immunogenicity; and methods of using such compositions to elicit an immunological or protective response. Throughout this specification, various documents are referred to in order to more fully describe the state of the art to which this invention pertains. These documents are each hereby incorporated herein by reference. Lyme borreliosis is the most prevalent tickborne disease in the United States as well as one of the most important tick-borne infectious diseases worldwide. The spirochete Borrelia burgdorferi is the causative agent

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for Lyme disease. Infection with B. burgdorferi produces local and systemic manifestations. Local symptoms that appear early after infection are a skin lesion at the site of the tick bite, termed erythema migrans. Weeks to months after infection, systemic manifestations that include rheumatic, cardiac and neurological symptoms appear. The early local phase of B. burgdorferi infection is easily treatable with antibiotics. However, the later systemic phases have proved to be more refractory to antibiotics. Web site: http://www.delphion.com/details?pn=US06538118__ •

Fusion protein of hEGF and human angiogenin and process for preparing the same Inventor(s): Han; Seung-Hee (Sungnam, KR), Kim; Seung-Ho (Seoul, KR), Kim; YoungMan (Sungnam, KR), Koo; Tai-Young (Suwon, KR), Lee; Byoung-Kwang (Sungnam, KR), Oh; Byung-Kwon (Sungnam, KR), Park; Myung-Hwan (Seoul, KR), Park; SeungKook (Sungnam, KR), Yoon; Jong-Myung (Sungnam, KR) Assignee(s): Daewoong Pharmaceutical Co., Ltd. (Kyunggi-do, KR) Patent Number: 6,541,619 Date filed: July 13, 2000 Abstract: The present invention provides a genetically engineered fusion protein consisting of hEGF that is internalized inside of the cells after tracing down the cancer cells expressing hEGF receptors and human angiogenin that is cytotoxic by degrading ribonucleotide upon internalization, a process for preparing a fusion protein in a large quantity by transforming E. coli with the expression vectors containing the gene encoding the fusion protein, and pharmaceutical application of the fusion protein as an anticancer agent. All components of the fusion protein form no antibodies and exhibit no immunotoxicity since they are derived from human. Each component alone is inactive to the cancer cells, however, once they are fused together, they kill the cancer cells selectively with a difference of 1000 fold in IC.sub.50 in spite of its low molecular weight. Therefore, the fusion protein of the present invention is capable of treating the cancer expressing hEGF receptors at high level without showing toxicity. Excerpt(s): The present invention relates to a fusion protein of human epidermal growth factor("hEGF") and human angiogenin, and a process for preparing the fusion protein, more specifically, to a fusion protein of hEGF that tracks down the cancer cells expressing hEGF receptors at high level following internalization and angiogenin that exhibits cytotoxicity by degrading ribonucleic acids upon internalization, a process for preparing the fusion protein which employs E. coli transformed with an expression vector encoding a gene for the fusion protein, and its therapeutic application as an anticanacer agent. Environmental pollution and increase in population of old-aged people cause increase of the rate of cancer by 5% every year. Cancer ranks first as the major cause of death among other diseases and accidents. Chemotherapy has been widely used as an effective way to prevent and cure cancer. However, it has been known that chemotherapy provokes various side-effects, e.g., attacking the normal cells as well as the cancer cells. Due to low specificity for the cancer cells and toxicity for the normal cells, numerous attempts have been made to develop anticancer agents with high specificity and low toxicity. The examples of such attempts include search for the drug with novel mode of action, development of drug delivery system and drug targeting, and use of a secondary agent to aid activity of a primary anticancer agent. Web site: http://www.delphion.com/details?pn=US06541619__

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Genes essential for microbial proliferation and antisense thereto Inventor(s): Forsyth; R. Allyn (San Diego, CA), Ohlsen; Kari (San Diego, CA), Zyskind; Judith W. (La Jolla, CA) Assignee(s): Elitra Pharmaceuticals, Inc. (San Diego, CA) Patent Number: 6,589,738 Date filed: November 9, 2000 Abstract: The sequences of nucleic acids encoding proteins required for E. coli proliferation are disclosed. The nucleic acids can be used to express proteins or portions thereof, to obtain antibodies capable of specifically binding to the expressed proteins, and to use those expressed proteins as a screen to isolate candidate molecules for rational drug discovery programs. The nucleic acids can also be used to screen for homologous genes that are required for proliferation in microorganisms other than E. coli. The nucleic acids can also be used to design expression vectors and secretion vectors. The nucleic acids of the present invention can also be used in various assay systems to screen for proliferation required genes in other organisms as well as to screen for antimicrobial agents. Excerpt(s): Since the discovery of penicillin, the use of antibiotics to treat the ravages of bacterial infections has saved millions of lives. With the advent of these "miracle drugs," for a time it was popularly believed that humanity might, once and for all, be saved from the scourge of bacterial infections. In fact, during the 1980s and early 1990s, many large pharmaceutical companies cut back or eliminated antibiotics research and development. They believed that infectious disease caused by bacteria finally had been conquered and that markets for new drugs were limited. Unfortunately, this belief was overly optimistic. The tide is beginning to turn in favor of the bacteria as reports of drug resistant bacteria become more frequent. The United States Centers for Disease Control announced that one of the most powerful known antibiotics, vancomycin, was unable to treat an infection of the common Staphylococcus aureus (staph). This organism is commonly found in our environment and is responsible for many nosocomial infections. The import of this announcement becomes clear when one considers that vancomycin was used for years to treat infections caused by stubborn strains of bacteria, like staph. In short, the bacteria are becoming resistant to our most powerful antibiotics. If this trend continues, it is conceivable that we will return to a time when what are presently considered minor bacterial infections are fatal diseases. There are a number of causes for the predicament in which practitioners of medical arts find themselves. Overprescription and improper prescription habits by some physicians have caused an indiscriminate increase in the availability of antibiotics to the public. The patient is also partly responsible, for even in instances where an antibiotic is the appropriate treatment, patients will often improperly use the drug, the result being yet another population of bacteria that is resistant, in whole or in part, to traditional antibiotics. Web site: http://www.delphion.com/details?pn=US06589738__

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High fidelity PCR cloning Inventor(s): Malo; Madhu Sudan (Watertown, MA) Assignee(s): SyntheGen Systems, Inc. (Medford, MA) Patent Number: 6,566,067 Date filed: February 14, 2001

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Abstract: The present invention describes a methodology for generating high fidelity PCR products, and also cloning of such high fidelity PCR products in a suitable vector. Generation of polymerase-induced mutant fraction of target sequences during PCR amplification is linearly proportional to the number of doublings of the target sequences. Thus the high fidelity PCR products are generated by minimizing the number of doublings of the target nucleic acid sequences during PCR amplification. Minimization of number of doublings of the target sequences is achieved by reducing the number of cycles of PCR amplification of the target sequences. The high fidelity PCR products thus obtained are then cloned into a suitable vector. As an example, a 960 bp target sequence from E. coli DNA was PCR-amplified only for 3 cycles, and it was then directly cloned into a positive selection cloning vector pRGR2Ap. The functional analysis of the inserts in all clones showed that the clones carried functionally wild-type DNA fragments, and hence the inserts most probably carry no mutation. Cloning of PCR products obtained from 3 cycles of amplification, instead of 30 cycles of amplification, theoretically achieves 10-fold reduction of mutations in the cloned fragments. The invention also contemplates cloning of a target cDNA obtained by primer extension. Excerpt(s): The present invention relates to a methodology for high fidelity cloning of target nucleic acids. The invention involves application of polymerase chain reaction (PCR) for a few cycles, which minimizes number of doublings of target sequences, and hence greatly reduces generation of polymerase-induced mutant fraction in PCR products. The invention also describes cloning of such high fidelity PCR products in a positive selection vector. Polymerase chain reaction or PCR (Saiki et al., 1985, Science 230, 1350-1354; Mullis and Faloona, 1987, Method Enzymol. 155, 335-350; U.S. Pat. Nos. 4,683,195; 4,683,202 and 4,965,188) has revolutionized amplification of target nucleic acids. The technique involves repeated cycles of denaturation of template nucleic acid molecules, sequence-specific primer annealing and primer extension using DNA polymerase thus resulting in an exponential amplification of the target nucleic acids. Usually, 30 cycles of PCR result in one million-fold amplification of target sequences from 20 doublings. The PCR product itself could be used for diagnosis, quantitation of the template, direct sequencing and some other applications (U.S. Pat. Nos. 5,856,144; 5,487,993 and 5,891,687). However, for applications such as mutation analysis, identification of polymorphic transcripts, making RNA probes, sequencing, gene expression etc., usually a large quantity of DNA is needed. Thus it is necessary to isolate a bacterial clone carrying the PCR generated target DNA fragment in a cloning vector. Web site: http://www.delphion.com/details?pn=US06566067__ •

Human porphobilinogen deaminase sequences Inventor(s): Fogh; Jens (Lynge, DK), Gellerfors; Par (Lidingo, SE) Assignee(s): Hemebiotech A/S (Hillerod, DK) Patent Number: 6,537,777 Date filed: July 22, 1999 Abstract: A method for treatment or prophylaxis of disease caused by deficiency, in a subject, of an enzyme belonging to the heme biosynthetic pathway, the method comprising administering, to the subject, an effective amount of a catalyst which is an enzyme or an enzymatically equivalent part or analogue thereof. The disease is selected from the group consisting of acute intermittent porphyria (AIP), ALA deficiency porphyria (ADP), Porphyria cutanea tarda (PCT), Hereditary coproporphyria (HCP),

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Harderoporphyria (HDP), Variegata prophyria (VP), Congenital erthropoetic porphyria (CEP), Erythropoietic protoporphyria (EPP), and Hepatoerythropoietic porphyria (HEP). The catalyst is one or more enzymes selected from the group consisting of deltaaminolevulininic acid synthetase, delta-aminolevulinic acid dehydratase (ALAD), porphobilinogen deaminase (PBGD), uroporphyrinogen III cosythetase, uroporphyrinogen decarboxylase, coproporphyrinogen oxidase, protoporphyrinogen oxidase, and ferrochelatase, or an enzymatically equivalent part or analogue thereof. In addition the invention relates to the use of PBGD, to human recombinant PBGD and to a method of gene therapy. The invention also relates to an expression plasmid pExp1-M2BB (Seq. ID No. 1) and to use of a DNA fragment, the EcoRI-Hind III linear fragment (seq. ID No. 2), used for transformation in the hemC disruption strategy for production of rhPBGD expressed in E. coli. Excerpt(s): The present invention relates to novel methods of treating and preventing disease caused by absence or deficiency of the activity of enzymes belonging to the heme biosynthetic pathway. More specifically, the invention pertains to methods of alleviating the symptoms of certain porphyrias, notably acute intermittent porphyria including gene therapy, therapy with a combination of encymatically active substances and therapy with recombinant produced enzymes such as PBGD. In addition the invention relates to an expression plasmid and a linear DNA fragment for use in the production of rhPBGD. Heme is a vital molecule for life in all living higher animal species. Heme is involved in such important processes as oxygen transportation (haemoglobin), drug detoxification (Cytochrome P450), and electron transfer for the generation of chemical energy (ATP) during oxidative phosphorylation in mitochondria. Important regulation of the heme biosynthetic pathway is delivered by the end product of the metabolic pathway, namely heme, which exerts a negative inhibition on the first rate-limiting enzymatic step (Conducted by delta-aminolevulinic-synthetase) in the heme biosynthetic pathway (Strand et al. 1970, Proc. Natl. Acad. Sci. 67, 1315-1320). Web site: http://www.delphion.com/details?pn=US06537777__ •

Method and apparatus for water purification Inventor(s): Beckius; Robert (Richland, WA), Call; Charles J. (Pasco, WA), Hong; SeungHo (Richland, WA), Merrill; Ezra (Albuquerque, NM), Powell; Mike (Kennewick, WA), Shekarriz; Alireza (Columbia, MD) Assignee(s): MesoSystems Technology, Inc. (Kennewick, WA) Patent Number: 6,623,603 Date filed: October 19, 1999 Abstract: A method and apparatus for purifying water by using thermal and/or thermocatalytic processes. The method and apparatus are particularly useful for processing impure water to remove and/or deactivate toxic inorganic, organic, and/or biological species such as Sarin, mustard gas, phosgene, cyanogen chloride, anthrax, E. coli, Giardia cysts, salmonella, hepatitis, and Norwalk viruses. In the thermal process, contaminated water is heated (preferably superheated) forming steam, whereby a majority of inorganic and biological species are removed or deactivated from the water. The steam is then condensed, forming liquid purified water. In the thermocatalytic process, the steam is brought into contact with a hydrolysis catalyst, preferably in the form of a coated surface or replaceable catalyst element. The hydrolysis catalyst, which may be a metal oxide, thermocatalytically deactivates at least 90% of the organic or biological species in the water, converting them to less toxic organic species or non-

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viable biological species. Various embodiments of the apparatus are provided, including portable configurations. Each of the embodiments include at least one boiler, at least one condenser, and a water reservoir arranged in heat exchange relationship so as to improve an overall operating efficiency of the apparatus. The apparatus is heated using a portable stove or other heat source, and a counterflow heat exchanger preheats water that is to be vaporized and cools the purified liquid water formed in a condenser. Excerpt(s): The present invention generally concerns water purification, and more specifically, the purification of water containing toxic species, using thermal and thermocatalytic processes and apparatus. It is often necessary to purify water by removing inorganic, organic, and biological species from the water before it can be used or consumed. Methods for removing particulate and chemical species from water are well known, and include distillation, reverse osmosis, freezing, ionization, photocatalytic treatment, and carbon filtration. Examples of such methods are disclosed in U.S. Pat. Nos. 5,007,994; 5,227,053; 5,133,858; and 4,717,476. In addition, there are many well-known methods for destroying bacteria in water, including boiling, using submicron filtration, and disinfectant processes using chlorine, bromine, iodine, or other strong oxidizers. Treatment with heat or disinfectants may also be used sterilize water containing harmful viral agents. In many instances, it is desired to have access to a portable means for purifying water. For example, it is often impractical for campers, hikers, mountain climbers, and others who are outdoors for extended period of time, to rely on treated water that they would be required to carry throughout an outing extending over several days. In these instances, it will be preferable to rely on local water sources, such as streams or lakes, which typically contain various particulate and mineral contaminants, including dirt, salt, algae, etc., and also may contain bacterial or viral contaminants. Although the methods and devices discussed above might be used to purify water flowing in a stream or lake water, some of the methods are unsuitable for portable use, because, e.g., they require heavy or bulky equipment, or substantial mechanical or electrical power. In view of the problem, several portable water purification devices have been developed, including those disclosed in U.S. Pat. Nos. 5, 273,649; 5,268,093; 5,244,579; and 3,635,799. Web site: http://www.delphion.com/details?pn=US06623603__ •

Method for cloning and expression of AsiSI restriction endonuclease and AsiSI methylase in E. coli Inventor(s): Xu; Shuang-yong (Lexington, MA), Zhu; Zhenyu (Beverly, MA) Assignee(s): New England Biolabs, Inc. (Beverly, MA) Patent Number: 6,514,737 Date filed: August 20, 2001 Abstract: The present invention relates to recombinant DNA which encodes the AsiSI restriction endonuclease as well as AsiSI methylase, expression of AsiSI restriction endonuclease and AsiSI methylase in E. coli cells containing the recombinant DNA. Excerpt(s): The present invention relates to recombinant DNA encoding the AsiSI restriction endonuclease (endonuclease) as well as AsiSI methyltransferase (methylase), expression of AsiSI restriction endonuclease and methylase in E. coli cells containing the recombinant DNA. Type II restriction endonucleases are a class of enzymes that occur naturally in bacteria and in some viruses. When they are purified away from other bacterial/viral proteins, restriction endonucleases can be used in the laboratory to cleave

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DNA molecules into small fragments for molecular cloning and gene characterization. Restriction endonucleases recognize and bind particular sequences of nucleotides (the `recognition sequence`) on DNA molecules. Once bound, they cleave the molecule within (e.g. BamHI), to one side of (e.g. SapI), or to both sides (e.g. TspRI) of the recognition sequence. Different restriction endonucleases have affinity for different recognition sequences. Over two hundred and eleven restriction endonucleases with unique specificities have been identified among the many hundreds of bacterial species that have been examined to date (Roberts and Macelis, Nucl. Acids Res. 27:312-313, (1999)). Web site: http://www.delphion.com/details?pn=US06514737__ •

Method for detecting anti-Streptococcus pyogenes DNase B antibody in a test sample Inventor(s): Adams; Craig W. (Corona, CA), Belei; C. Marina (Anaheim, CA), Pang; Patty P. Y. (Rancho Cucamonga, CA) Assignee(s): Beckman Coulter, Inc. (Fullerton, CA) Patent Number: 6,632,614 Date filed: July 21, 1998 Abstract: The gene for Streptococcus pyogenes DNase B has been cloned and vectors incorporating the cloned DNA have been used to transform Escherichia coli, allowing efficient and rapid production of the DNase in E. coli without the necessity of growing large quantities of S. pyogenes. The enzyme can be produced with a leader peptide at its amino terminus. An improved method for the purification of naturally occurring S. pyogenes DNase B enzyme is also provided. The DNase B enzyme produced, either by purification of naturally occurring enzyme or by recombinant DNA techniques, can be used to generate antibodies and can also be used in immunochemical assays to detect the presence of anti-DNase B antibodies in serum as a marker of infection by S. pyogenes. Excerpt(s): This invention is directed to recombinant DNase B derived from the pathogenic bacterium Streptococcus pyogenes, methods for its production, and methods for its use. Despite advances in the prevention and treatment of bacterial infection, a number of bacterial pathogens remain serious problems in medical practice and continue to cause severe, even fatal disease. One of these pathogens is S. pyogenes. Among the diseases caused by S. pyogenes are streptococcal pharyngitis ("strep throat"), scarlet fever, and their suppurative complications, including cervical adenitis, otitis media, mastoiditis, peritonsillar abscesses, meningitis, pneumonitis, pneumonia, puerperal sepsis, cellulitis of the skin, impetigo, lymphangitis, erysipelas, acute glomerulonephritis, and rheumatic fever. Such infections often occur in hospitals (nosocomial infection), particularly in patients whose normal immune system functioning is suppressed. The latter category includes patients with AIDS, patients taking immunosuppressive drugs for cancer or to prevent transplant rejection, and patients having poor circulation, e.g., patients with diabetes. Web site: http://www.delphion.com/details?pn=US06632614__

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Method of making bioluminescent assay reagent based on non-viable E. coli Inventor(s): Isles; Katherine (Oxon, GB), Lewington; Jay (Bisley, GB), Primrose; Sandy (High Wycombe, GB) Assignee(s): Azur Environmental (Carlsbad, CA) Patent Number: 6,524,810 Date filed: December 1, 2000 Abstract: A cell-derived assay reagent prepared from cells which have been killed by treatment with an antibiotic selected from the bleomycin-phleomycin family of antibiotics but which retain a signal-generating metabolic activity such as bioluminescence. Excerpt(s): The use of bacteria with a signal-generating metabolic activity as indicators of toxicity is well established. UK patent number GB 2005018 describes a method of assaying a liquid sample for toxic substances which involves contacting a suspension of bioluminescent microorganisms with a sample suspected of containing a toxic substance and observing the change in the light output of the bioluminescent organisms as a result of contact with the suspected toxic substance. Furthermore, a toxicity monitoring system embodying the same assay principle, which is manufactured and sold under the Trade Mark Microtox.RTM., is in routine use in both environmental laboratories and for a variety of industrial applications. An improved toxicity assay method using bioluminescent bacteria, which can be used in a wider range of test conditions than the method of GB 2005018, is described in International patent application number WO 95/10767. The assay methods known in the prior art may utilize naturally occurring bioluminescent organisms, including Photobacterium phosphoreum and Vibrio fischeri. However, recent interest has focused on the use of genetically modified microorganisms which have been engineered to express bioluminescence. These genetically modified bioluminescent microorganisms usually express lux genes, encoding the enzyme luciferase, which have been cloned from a naturally occurring bioluminescent microorganism (E. A. Meighen (1994) Genetics of Bacterial Bioluminescence. Ann. Rev. Genet. 28: 117-139; Stewart, G. S. A. B. Jassin, S. A. A. and Denyer, S. P. (1993), Engineering Microbial bioluminescence and biosensor applications. In Molecular Diagnosis. Eds R. Rapley and M. R. Walker Blackwell Scientific Pubs/Oxford). A process for producing genetically modified bioluminescent microorganisms expressing lux genes cloned from Vibrio harveyi is described in U.S. Pat. No. 4,581,335. The use of genetically modified bioluminescent microorganisms in toxicity testing applications has several advantages over the use of naturally occurring microorganisms. For example, it is possible to engineer microorganisms with different sensitivities to a range of different toxic substances or to a single toxic substance. However, genetically modified microorganisms are subject to marketing restrictions as a result of government legislation and there is major concern relating to the deliberate release of genetically modified microorganisms into the environment as components of commercial products. This is particularly relevant with regard to toxicity testing which is often performed in the field rather than within the laboratory. The potential risk from release of potentially pathogenic genetically modified microorganisms into the environment where they may continue to grow in an uncontrollable manner has led to the introduction of legal restrictions on the use of genetically modified organisms in the field in many countries. Web site: http://www.delphion.com/details?pn=US06524810__

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Method of producing biologically active human acidic fibroblast growth factor and its use in promoting angiogenesis Inventor(s): Chernykh; Svitlana I. (Kiev, UA), Kordyum; Vitaliy A. (Kiev, UA), Slavchenko; Iryna Yu. (Kiev, UA), Stegmann; Thomas J. (Petersberg, DE), Vozianov; Oleksandr F. (Kiev, UA) Assignee(s): Phage Biotechnology Corporation (Tustin, CA) Patent Number: 6,642,026 Date filed: August 15, 2001 Abstract: The gene of human acidic fibroblast growth factor 155 (haFGF 155) has been obtained by chemical synthesis. The nucleotide sequence of haFGF 155 gene has been deduced on the basis of haFGF 155 amino acid sequence as described in the literature. The amino acid sequence of the synthesized haFGF 155 does not differ from those described in the literature. The nucleotide sequence of haFGF gene differs from those described previously. For chemical synthesis of haFGF 155 gene, codons were used which are the ones most often used by E. coli in highly expressed E. coli proteins. A plasmid with haPGF 155 (phaFGF 155) gene was obtained and was used to transform E. coli. Production of haFGF 154 protein was achieved by cultivation of the producer strain under conditions which slow down the lytic development of lambda phage. The haFGF 154 protein accumulated in culture medium in a soluble condition as a result of the producer strain cells lysis by the lambda phage. The haFGF 154 protein constituted 20% of the soluble protein accumulated in the culture medium and its biological activity was demonstrated by its ability to generate new vessels (angiogenesis). The initiator methionine residue at position 1 of the FGF 155 protein was completely removed during protein synthesis resulting in an FGF 154 amino acid product. The use of the phagedependent method to produce other forms of the haFGF protein is also disclosed. Excerpt(s): The field of the invention relates to methods of producing a recombinant fibroblast growth factor protein and its use in promoting angiogenesis. Fibroblast growth factors (FGF) are nine structurally related polypeptides, which are potent regulators of cell proliferation, differentiation and normal development. They also take part in pathological processes of tumorogenesis and metastasis (Galzie, et al. Biochem. Cell Biol. (1997) 75: 669-685). They are potent mitogens and differentiation factors for a broad range of mesoderm and neuroectoderm derived cells, including endothelial cells. The heparin proteoglycans, heparin or heparin sulfate, bind several FGF molecules together as a complex which are presented to the FGF receptors. FGF proteins bind to their receptors resulting in the activation of protein tyrosine kinases. The phosphorylation of these tyrosine kinases initiates multiple signals including the transcription of new mRNA's. Web site: http://www.delphion.com/details?pn=US06642026__

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Methods and compositions to identify swine genetically resistant to F18 E. coli associated diseases Inventor(s): Bosworth; Brad T. (Littleton, NC), Vogeli; Peter (Zurich, CH) Assignee(s): Biotechnology Research & Development Corp. (Peoria, IL), Swiss Federal Institute of Technology (Zurich, CH), The United States of America as represented by the Secretary of Agriculture (Washington, DC) Patent Number: 6,596,923 Date filed: November 19, 1999 Abstract: The present invention provides non-invasive methods and compositions to differentiate, with a high level of sensitivity and specificity, swine that are genetically susceptible to diseases associated with F18 E. coli infection, from resistant swine. DNA polymorphisms in the swine alpha (1,2) fucosyltransferase 1 (FUT1) gene were used to differentiate resistant from susceptible swine. The invention includes a polypeptide with amino acid substitutions, encoded by the nucleotide polymorphisms, a molecular diagnostic assay, and a kit for the differentiation, of E. coli F18-adhesion resistant, heterozygous (Carrier) and homozygous susceptible pigs. The molecular test identifies susceptibility to oedema disease and postweaning diarrhea with high sensitivity and specificity, therefore, is useful to swine breeder in their effort to enhance for resistance. Information on the polymorphisms of the present invention provides insight into causation and treatment of E. coli associated intestinal disorders. Excerpt(s): Compositions and non-invasive methods are provided for the identification of swine genetically resistant to E. coli bacteria supplied with fimbriae F18. DNA polymorphisms in the swine alpha (1,2) fucosyltransferase (FUT1) gene were identified that differentiate resistant from susceptible swine and provide a diagnostic test useful for swine breeders. A major problem in breeding swine is to keep them disease-free. Intestinal disorders postweaning are a particular problem. A limited number of serotypes of toxigenic Escherichia (E.) Coli strains are the causative agents of oedema disease and postweaning diarrhea in swine which induce serious economic losses, especially among piglets aged 4 to 12 weeks, in swine breeding farms all over the world. The typical symptoms of oedema disease are neurological signs such as ataxia, convulsions and paralysis. At post mortem examination, oedema is typically present at characteristic sites such as eyelids and forehead, stomach wall and mesocolon. The diseases are cause be Shiga-like toxin-II variant and enterotoxins LT, Sta, Stb respectively, produced by E. coli that colonize the surface of the small intestine without effecting major morphological changes of the enterocytes (Cells in the intestine). Certain types of bacterial E. coli strains, F18, F4 and K88 are major lethal villains in this regard. "Oedema disease of pigs is an enterotoxaemia characterized by generalized vascular damage. The latter is cause by a toxin, Shiga-like toxin II variant, produced by certain strains of E. coli" (Bertschinger et al., 1993). The E. coli are distinguished by their pili types, a group of adhesive fimbriae that are related are designated e.g., K88 or F18 (Vogeli et al., 1997). Not all swine succumb to E. coli infections. Colonization depends on adherence of the bacteria to the enterocytes which is mediated by the bacterial fimbriae designated e.g., K88 or F18. Susceptibility to adhesion, i.e. expression of receptors in swine for binding the fimbriae, has been shown to be genetically controlled by the host and is inherited as a dominant trait with, in the case of F18, B being the susceptibility allele and b the resistance allele. (Vogeli et al., 1996; Meijerink et al., 1996). The genetic locus for this E. coli F18-receptor (ECF18R) has been mapped to porcine chromosome 6 (SSC6), based on its close genetic linkage to the S locus and other loci of

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the halothane (HAL) linkage group on chromosome 6. The receptor for K88 E. coli is on chromosome 13. Web site: http://www.delphion.com/details?pn=US06596923__ •

Methods for bioremediation by degrading toluene Inventor(s): Coschigano; Peter W. (The Plains, OH) Assignee(s): Ohio University (Athens, OH) Patent Number: 6,551,814 Date filed: May 4, 1998 Abstract: Compositions and methods for the degradation of compounds contained in a liquid or solid waste stream are provided. Genes encoding toluene-degrading enzymes are also provided. The enzymes have homology to the E. coli pyruvate formate lyase and pyruvate formate lyase activator. Excerpt(s): This invention relates to biological treatment of organic compounds, and particularly to the degradation of toluene and toluene analogues. Industrial processes that use or generate toxic organic compounds (e.g., toluene, benzene, xylenes) has lead to the contamination of nearby water and land. Such compounds are among the most water soluble of all gasoline components and can also enter aquatic environments from many sources such as gasoline underground storage tanks, leaks, and spills. Most approaches to decontamination or "remediation" involve stopping the local dumping of such compounds and transport of the waste to another area for containment. This is costly and does not eliminate the hazard. Web site: http://www.delphion.com/details?pn=US06551814__

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Methods of producing and using virulence attenuated poxR mutant bacteria Inventor(s): Kaniga; Kone (St. Louis, MO) Assignee(s): Megan Health, Inc. (St. Louis, MO) Patent Number: 6,537,558 Date filed: March 31, 1997 Abstract: Disclosed are bacteria having virulence attenuated by a mutation to the regulatory gene poxR. Also disclosed is a method of producing bacteria having virulence attenuated by mutating to the regulatory gene poxR. Such bacteria are useful for inducing an immune response in an animal or human against virulent forms of the bacteria with reduced risk of a virulent infection. Such bacteria are also useful to allow use of normally virulent bacteria as research tools with reduced risk of virulent infection. In a preferred embodiment, poxR attenuated bacteria can be used as a vaccine to induce immunoprotection in an animal against virulent forms of the bacteria. The disclosed bacteria can also be used as hosts for the expression of heterologous genes and proteins or to deliver DNA for genetic immunization. Attenuated bacteria with such expression can be used, for example, to deliver and present heterologous antigens to the immune system of an animal. Such presentation on live bacteria can lead to improved stimulation of an immune response by the animal to the antigens. It has been discovered that bacteria harboring a poxR mutation has significantly reduced virulence. Also disclosed is the nucleotide sequence of the poxR gene from Salmonella typhimurium,

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and the amino acid sequence of the encoded protein. The encoded protein has 325 amino acids and has significant sequence similarity to previously uncharacterized open reading frames in E. coli and Haemophilus influenzae. Excerpt(s): The disclosed invention is in the general areas of bacteria with attenuated virulence and live bacterial vaccines. The poxA gene (Van Dyk et al., J. Bacteriology169(10):4540-4546 (1987)), is a regulatory gene affecting expression of pyruvate oxidase (Chang and Cronan, J. Bacteriology 151(3): 1279-1289 (1982)). The poxA gene of E. coli is located at min 94. Enzymological and immunological data indicate that mutations in poxa have an 8 to 10-fold decrease in pyruvate oxidase levels (Chang and Cronan (1982); Chang and Cronan, J. Bacteriol. 154:756-762 (1983)). It has also been reported that poxA mutants grow more slowly than the isogenic wild-type in both minimal and rich media, while poxB mutants exhibit normal growth. Van Dyk and LaRossa, J. Bacteriol. 165(2):386-392 (1986), isolated 15 mutant Salmonella typhimurium strains sensitive to the herbicide sulfometuron methyl (SM) [N-[(4,6-dimethylpyrimidin2-yl)aminocarbonyl]-2-methoxycarbonyl-benzenesu lfonamide], following Tn10 mutagenesis. Among these SM-hypersensitive mutations, a poxA mutation was identified and mapped to the 94 min region of S. typhimurium genetic map (Van Dyk et al. (1987)), a location analogous to that of poxA in E. coli. The S. typhimurium poxA mutant, similarly to the E. coli poxA mutant, had reduced pyruvate oxidase activity and reduced growth rates (Van Dyk et al. (1987)). Furthermore, the E. coli and S. typhimurium poxA mutants shared several additional phenotypes including hypersensitivity to SM, to.alpha.-ketobutyrate, and to a wide range of bacterial growth inhibitors, such as antibiotics, amino acid analogs and dyes (Van Dyk et al. (1987)). The immune system of animals is especially suited to reacting to and eliminating microorganisms which infect the animal. The sustained presence of the full range of antigens expressed by infecting microorganisms provide a stimulating target for the immune system. It is likely that these characteristics lead to the superior efficacy, on average, of vaccines using live attenuated virus. For similar reasons, live bacterial vaccines have been developed that express a desired antigen and colonize the intestinal tract of animals (Curtiss et al., Curr. Topics Micro. Immun. 146:35-49 (1989); Curtiss, Attenuated Salmonella Strains as Live Vectors for the Expression of Foreign Antigens, in New Generation Vaccines (Woodrow and Levine, eds., Marcel Dekker, New York, 1990) pages 161-188; Schodel, Infection 20(1): 1-8 (1992); Cardenas and Clements, Clinical Micro. Rev. 5(3):328-342 (1992)). Most work to date has used avirulent Salmonella typhimuriumstrains synthesizing various foreign antigens for immunization of mice, chickens and pigs. Several avirulent S. typhi vectors have been evaluated in human volunteers (Tacket et al., Infect. Immun.60:536-541 (1992)) and several phase I clinical trials with recombinant avirulent S. typhi strains are in progress in the U.S. and Europe. An important safety advantage of the live attenuated bacterial vaccine vectors as compared to the use of viral vector based vaccines is the ability to treat an immunized patient with oral ciprofloxacin or amoxicillin, should an adverse reaction occur. Web site: http://www.delphion.com/details?pn=US06537558__

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Microfabricated microbial growth assay method and apparatus Inventor(s): Blattner; Frederick R. (Madison, WI), Van der Weide; Daniel W. (Madison, WI) Assignee(s): Wisconsin Alumni Research Foundation (Madison, WI) Patent Number: 6,649,402 Date filed: June 22, 2001 Abstract: Microbial growth assays are carried out utilizing assay apparatus having a base plate with a plurality of microbial growth assay wells, each well having a liquid content of 30.mu.l or less. Electrodes are coupled together through the wells and electrical connectors are connected to the electrodes to allow the effect of the content of the wells to be measured by measuring the capacitance or resistance or both between the electrodes at each well, with the change in the capacitance or resistance in each well over time being correlated with the extent of growth of a bacterium introduced into the well with a growth medium. The small size of the microwells causes the growth of bacteria in the well to quickly show a change in the electrical properties of the well, particularly in the capacitance or resistance between the electrodes at each well, with growth to saturation occurring for common bacteria such as E. coli in a few hours or less. High density base plates may be tested with a large variety of substances that may have an effect on the growth of the bacteria in the well over a relatively short period of time, allowing high throughput while maintaining the accuracy of the test. Excerpt(s): This invention pertains generally to the field of devices and techniques for microbial growth assays and to the screening of substances for their effect on cell growth. Several types of microbial growth assays have been developed, some with commercial success, but most of these assays rely on flow-through chambers, large (greater than ml) sample sizes, or long incubation periods, which limits the suitability of such assays for high-throughput screening. Targeted against a range of wild-type or enfeebled strains of various pathogenic bacteria, the growth assay is the simplest and most direct measurement of drug efficacy, and represents the means by which almost all antimicrobial drugs have been discovered. The classic culture methods used by Fleming for the discovery of penicillin are still applied in clinical diagnostics today, and have been the primary path for drug discovery as well, even though response times are typically measured in days. Faster techniques that have been developed for measuring cell concentrations still employ relatively large volumes. These techniques and devices include optical measures of turbidity, flow cytometers, biomass measurements with microbalances, and electronic counting techniques, predominantly the Coulter counter. These techniques can still take hours to respond, given the large populations being measured. Because of the small size of most bacteria, conventional optical measurements of scattering or attenuation lack the combination of speed and selectivity needed for high-density arrays, in part because the dielectric contrast between the cells and their medium is low in the visible portion of the electromagnetic spectrum. Highfrequency electrical characterization, however, is attractive for microbial growth assays because it circumvents the need for image analysis and it is readily scalable to manipulating and screening sub-visible particles, such as viruses. See D. W. van der Weide, "Microscopes for the sub-visible: scanning the near field in the microwave through infrared," Optics and Photonics News, 1998, Vol. 9, pp. 40-45; D. W. E. Allsopp, et al., "Impedance technique for measuring dielectrophoretic collection of microbiological particles," Journal of Physics D (Applied Physics), 1999, Vol. 32(9), pp. 1066-74. Although it operates at low frequencies, the Coulter counter exploits the contrast in conductivity between cells and their medium as the cells traverse an aperture

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between two chambers: a change in resistance is a discrete event corresponding to the presence of a cell in the aperture. Other more sophisticated high-frequency techniques measure not only the real part (resistance/conductance) but also the imaginary part (reactance/susceptance) of the cells' impedance/admittance, since cells display a complex permittivity. See R. Pethig, et al., "The passive electrical properties of biological systems: their significance in physiology, biophysics and biotechnology," Phys Med Biol, 1987, Vol. 32(8), pp. 933-70; A. D. Shaw, et al., "Rapid analysis of high-dimensional bioprocesses using multivariate spectroscopies and advanced chemometrics," Adv Biochem Eng Biotechnol, 2000, Vol. 66, pp. 83-113. Web site: http://www.delphion.com/details?pn=US06649402__ •

Modified E. coli enterotoxin II signal peptide and a microorganism expressing a fusion protein of a said peptide and a heterologous protein Inventor(s): Choi; Jay-Do (Seoul, KR), Choi; Ki-Doo (Seoul, KR), Jung; Sung-Youb (Seoul, KR), Kwon; Se-Chang (Seoul, KR), Lee; Gwan-Sun (Seoul, KR), Shin; Hoon (Seoul, KR) Assignee(s): Hanmi Pharm. Co., Ltd. (KR) Patent Number: 6,605,697 Date filed: March 7, 2001 Abstract: A heterologous protein is produced by: (i) culturing a microorganism transformed with an expression vector comprising a gene encoding a modified E. coli enterotoxin II signal peptide fused with the heterologous protein to produce and secrete the heterologous protein to periplasm, the modified E. coli enterotoxin II signal peptide being obtained by replacing at least one of the 2nd, 4th, 5th, 12th, 20th, and 22nd amino acids of E. coli enterotoxin II signal peptide of the following amino acid sequence (SEQ ID NO: 1) with another amino acid, with the proviso that at least one of the 2nd and 4th amino acid of the modified peptide is lysine; and (ii) recovering the heterologous protein from the periplasm. Excerpt(s): The present invention relates to a modified E. coli enterotoxin II signal peptide, a gene encoding said peptide, a vector comprising said gene fused with a gene encoding a heterologous protein, a microorganism transformed with said vector, and a process for producing the heterologous protein using said microorganism. Many heterologous proteins have been produced using genetically engineered host microorganisms by an intracellular method or secreting method. In the intracellular method, a gene encoding a heterologous protein is expressed and accumulated in the cytoplasm of a microorganism. Although this method is known to give a relatively high heterologous protein yield, the expressed heterologous protein is not of a natural active form but methionylated at the N-terminus. Further, the biologically inactive heterologous protein produced by this method often forms insoluble inclusion bodies which must be solubilized and converted into a naturized, active form by a refolding process. Web site: http://www.delphion.com/details?pn=US06605697__

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Molecular mimetics of unique Neisseria meningitidis serogroup B epitopes Inventor(s): Granoff; Dan M. (Berkeley, CA), Moe; Gregory R. (Alameda, CA) Assignee(s): Children's Hospital Medical Center of Northern California (Oakland, CA), Chiron Corporation (Emeryville, CA) Patent Number: 6,642,354 Date filed: July 23, 2001 Abstract: Novel bactericidal antibodies against Neisseria meningitidis serogroup B ("MenB") are disclosed. The antibodies either do not cross-react or minimally cross-react with host tissue polysialic acid and hence pose minimal risk of autoimmune activity. The antibodies are used to identify molecular mimetics of unique epitopes found on MenB or E. coli K1. Examples of such peptide mimetics are described that elicit serum antibody capable of activating complement-mediated bacteriolysis of MenB. Vaccine compositions containing such mimetics can be used to prevent MenB or E. coli K1 disease without the risk of evoking autoantibody. Excerpt(s): The present invention pertains generally to bacterial pathogens. In particular, the invention relates to antibodies that elicit functional activity against Neisseria meningitidis serogroup B and also lack autoimmune activity, methods of obtaining and using the same, as well as molecular mimetics identified using the antibodies. Neisseria meningitidis is a causative agent of bacterial meningitis and sepsis. Meningococci are divided into serological groups based on the immunological characteristics of capsular and cell wall antigens. Currently recognized serogroups include A, B, C, D, W-135, X, Y, Z and 29E. The polysaccharides responsible for the serogroup specificity have been purified from several of these groups, including A, B, C, D, W-135 and Y. N. meningitidis serogroup B ("MenB") accounts for approximately 50 percent of bacterial meningitis in infants and children residing in the U.S. and Europe. The organism also causes fatal sepsis in young adults. In adolescents, experimental MenB vaccines consisting of outer membrane protein (OMP) vesicles have been found to be approximately 50% protective. However, no protection has been observed in vaccinated infants and children, the age groups at greatest risk of disease. Additionally, OMP vaccines are serotype- and subtype-specific, and the dominant MenB strains are subject to both geographic and temporal variation, limiting the usefulness of such vaccines. Web site: http://www.delphion.com/details?pn=US06642354__

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Mutant E. coli strains, and their use for producing recombinant polypeptides Inventor(s): Lopez; Pascal (Saint-Laurent-du-Pont, FR), Dreyfus; Marc (Paris, FR) Assignee(s): Centre National de la Recherche Scientifique (Paris Cedex, FR) Patent Number: 6,632,639 Date filed: May 17, 2001 Abstract: The invention concerns the use of Escherichia coli (E. coli) strains whereof the gene coding for the Rnase E comprises a mutation such that the enzyme produced when said mutated gene is expressed no longer has a degrading activity on mRNA, said mutation more significantly not affecting the growth of E. coli strains, for implementing a method for producing specific exogenous recombinant polypeptides. Excerpt(s): The invention concerns certain mutant E. coli strains, and their use for performing processes for producing recombinant polypeptides. Genomic study of

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higher organisms, micro-organisms, and viruses almost invariably requires, in addition to the cloning of their genes, large-scale production of their products (proteins), so as for example to obtain antibodies or to perform biochemical or crystallographic studies. From the applications viewpoint, the utilization in the medical field of numerous human peptides and proteins also requires expression of corresponding genes in heterologous organisms. Web site: http://www.delphion.com/details?pn=US06632639__ •

Mutant of RNA polymerases with increased stability Inventor(s): Liao; Hans (Eden Prairie, MN), Sugiyama; Akio (Tsuruga, JP), van Gemen; Bob (Almere, NL) Assignee(s): Akzo Nobel N.V. (NL) Patent Number: 6,524,828 Date filed: June 5, 2001 Abstract: The present application relates to mutated RNA polymerases from bacteriophages that have increased stability, for example under high temperature conditions. One example of bacteriophage encoded RNA polymerase is the T7 RNA polymerase. T7 is a bacteriophage capable of infecting E. coli cells. Examples of other E. coli infecting T7-like bacteriophages are T3,.o slashed.I,.o slashed.II, W31, H, Y, A1, croC21, C22 and C23. An example of a Salmonella typhimurium infecting bacteriophage is SP6. The present invention is concerned with the RNA polymerases of T7-like bacteriophages that have been mutated. Due to these mutations the RNAP's have an increased stability. Preferred mutated RNA polymerases according to the invention are mutant RNA polymerases from T7 or SP3 bacteriophages. Due to the high homology between these enzymes, mutations in the T7 gene 1 sequence are likely to have the same effect in the corresponding gene sequence of the T3 bacteriophage. An especially preferred embodiment of the present invention is a T7 RNA polymerase with a serine to proline amino acid change in the protein at position 633 of the amino acid sequence. Since there is 80% homology between the T7 RNA polymerase and the T3 RNA polymerase the same effects of the 633 serine.fwdarw.proline mutation in the T7 gene may be expected for a 634 serine.fwdarw.proline amino acid mutation in the T3 RNA polymerase. Excerpt(s): The RNA polymerases of bacteriophages have high selectivity for their own promoter sequence. The T7 RNA polymerase will bind the T7 RNA polymerase promoter sequence but not one of the other bacteriophage promoter sequences. The high promoter specificity ensures that the bacteriophage transcription reaction is only directed to its own genome and not the host genome. The entire nucleotide sequence of the T7 bacteriophage is known and the phage RNA polymerase is encoded by T7 gene 1. Other RNA polymerases that resemble the T7 RNA polymeraselare the RNA polymerases of bacteriophages SP6 and T3. The T3 RNAP shows about 80% homology with the T7 RNAP. The T7 gene 1 has been cloned and expressed in bacteria allowing the production of large quantities of the enzyme (Studier et al., U.S. Pat. No. 4,952,496). The T7 98,6 Kda. T7 RNA polymerase does not require any auxiliary factors for accurate transcription. The enzyme alone is capable of recognising it's promoters, initiating transcription, elongating the RNA transcript and terminating transcription. T7 RNA polymerase is very efficient in transcribing DNA from its own promoters and elongates RNA five times faster compared to E. coli RNA polymerase. Their selectivity, activity

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and ability to produce complete transcripts make the polymerases from bacteriophages very useful for a variety of purposes. Web site: http://www.delphion.com/details?pn=US06524828__ •

Phosphopantetheinyl transferases and uses thereof Inventor(s): Gehring; Amy M. (Beulah, MI), Lambalot; Ralph H. (Wrentham, MA), Reid; Ralph (San Francisco, CA), Walsh; Christopher T. (Wellesley, MA) Assignee(s): President and Fellows of Harvard College (Cambridge, MA), The Regents of the University of California (Oakland, CA) Patent Number: 6,579,695 Date filed: October 11, 1996 Abstract: The invention pertains to isolated phosphopantetheinyl transferases, such as the E. coli acyl carrier protein synthase, which transfer a phosphopantetheinyl group onto a substrate. The enzyme can be purified from a natural source, produced recombinantly, or synthetically. Accordingly, the invention provides compositions and kits including phosphopantetheinyl transferases and host cells expressing phosphopantetheinyl transferases. The invention also provides nucleic acids encoding phosphopantetheinyl transferases and vectors comprising such nucleic acids. The invention further provides methods for phosphopantetheinylating a substrate in vitro or in vivo and methods for producing antibiotics in vitro or in vivo. Excerpt(s): Acyl carrier protein (ACP) is a small acidic protein (8,800 Da) responsible for acyl group activation in fatty acid biosynthesis. The gene encoding ACP (acpP) has been cloned and overexpressed (Rawlings, M. and Cronan, J. E., Jr. (1992) J. Biol. Chem., 267, 5751-5754; Jones, A. L., et al. (1993) Biochem. Soc. Trans., 21, 202S) and the solution structure of ACP has been solved by NMR spectroscopy (Holak, T. et al. (1988) Eur. J. Biochem. 175:9-15). Homologs of E. coli ACP exist throughout nature in two forms; either as an integral domain of a much larger multifunctional enzyme (type I) or as a discrete protein capable of associating with several other enzymes constituting a multienzyme synthase complex (type II). In these two forms, ACPs play central roles in a broad range of other biosynthetic pathways that depend on iterative acyl transfer steps, including polyketide (Shen, B., et al. (1992) J. Bacteriol. 174:3818-3821), nonribosomal peptide (Baldwin, J. E., et al. (1991) J. Antibiot. 44:241-247), and depsipeptide biosynthesis (Rusnak, F., et al. (1991) Biochemistry 30:2916-2927) as well as in the transacylation of oligosaccharides (Geiger, O., et al. (1991) J. Bacteriol. 173:2872-2878) and proteins (Issartel, J. P., et al. (1991) Nature 351:759-761). A definitive feature of ACP is the 4'-phosphopantetheine (4'-PP) prosthetic group (Majerus, P. W. et al. (1965) Proc. Natl. Acad. Sci. USA 53:410-417). 4'-PP is attached through a phosphodiester linkage to a conserved serine residue found in all ACPs. Acyl groups of the many substrates recognized by type I and type II ACPs are activated for acyl transfer through a thioester linkage to the terminal cysteamine thiol of the 4'-PP moiety. The.beta.-alanyl and pantothenate portions of the 4'-PP structure are believed to serve as a tether between the phosphodiester-ACP linkage and the terminal thioester, suggesting that 4'-PP may function as a swinging arm, shuttling growing acyl chains between various active sites, e.g. as in the sequential addition of 11 amino acids by the 800 kDa cyclosporin synthetase (Lawen, A. and Zocher, R. (1990) J. Biol. Chem. 265:11355-11360). Holo-ACP synthase (holo-ACPS) transfers the 4'-PP moiety from Coenzyme A (CoA) to Ser-36 of apo-ACP to produce holo-ACP and 3',5'-ADP in a Mg.sup.2+ dependent reaction. The (acyl carrier synthase protein) ACPS from E. coli was partially purified 780-fold from

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crude extracts (Elovson, J. and Vagelos, P. R. (1968) J. Biol. Chem. 243:3603-3611), and the ACPS from spinach has been partially purified (Elhussein, S. A., et al. (1988) Biochem. J. 252:39-45), but remarkably little has been shown about the mechanism or specificity of this post-translational phosphopantetheinylation process. A mutant of E. coli conditionally defective in the synthesis of holo-ACP has been identified and the mutant phenotype attributed to an altered holo-ACP synthase activity (Polacco, M. L. and Cronan, J. E., Jr. (1981) J. Biol. Chem. 256:5750-5754). Web site: http://www.delphion.com/details?pn=US06579695__ •

Polyhydroxybutyrate polymerase Inventor(s): Peoples; Oliver P. (Arlington, MA), Sinskey; Anthony J. (Boston, MA) Assignee(s): Massachusetts Institute of Technology (Cambridge, MA) Patent Number: 6,528,706 Date filed: August 21, 2001 Abstract: A method for controlling and modifying biopolymer synthesis by manipulation of the genetics and enzymology of synthesis of polyhydroxybutyrate (PHB) and polyhydroxyalkanoate (PHA) polyesters at the molecular level in procaryotic and eukaryotic cells, especially plants. Examples demonstrate the isolation, characterization, and expression of the genes involved in the production of PHB and PHA polymers. Genes encoding the enzymes in the PHB and PHA synthetic pathway (beta-ketothiolase, acetoacetyl-CoA reductase and PHB polymerase or PHA polymerase) from Zoogloea ramigera strain I-16-M, Alcaligenes eutrophus, Nocardia salmonicolur, and Psuedomonas olevarans were identified or isolated and expressed in a non-PHB producing organism, E. coli. Specific modifications to the polymers include variation in the chain length of the polymers and incorporation of different monomers into the polymers to produce co-polymers with different physical properties. Excerpt(s): Synthesis by bacteria has long been the only means for production of many of the more complex biopolymers. Only recently have pathways for the synthesis of these polymers been determined. Much effort has gone into the isolation of the various enzymes and cofactors involved in these pathways. Regulation of their expression has largely been empirical, i.e., the concentration of nutrients or other factors such as oxygen level have been altered and the effect on polymer production and composition measured. In order to have control over the production of these complex biopolymers, and to modify them in a specific fashion, it is necessary to design a system for determining the chemical steps required for their synthesis; to isolate and characterize the proteins responsible for these chemical steps; to isolate, sequence, and clone the genes encoding these proteins; and to identify, characterize, and utilize the mechanisms for regulation of the rate and level of the expression of these genes. Polyhydroxybutyrate, a commercially useful complex biopolymer, is an intracellular reserve material produced by a large number of bacteria. Poly-beta-hydroxybutyrate (PHB), the polymeric ester of D(-)-3-hydroxybutyrate, was first discovered in Bacillus megaterium in 1925. Both the chemical and physical properties of this unique polyester have made it an attractive biomaterial for extensive study. PHB has a variety of potential applications, including utility as a biodegradable/thermoplastic material, as a source of chiral centers for the organic synthesis of certain antibiotics, and as a matrix for drug delivery and bone replacement. In vivo, the polymer is degraded internally to hydroxybutyrate, a normal constituent of human blood.

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Web site: http://www.delphion.com/details?pn=US06528706__ •

Polynucleotide encoding a mutant Rhodotorula glutinis tyrosine ammonia lyase polypeptide Inventor(s): Tang; Xiao-Song (Hockessin, DE) Assignee(s): E. I. du Pont de Nemours and Company (Wilmington, DE) Patent Number: 6,521,748 Date filed: January 19, 2001 Abstract: The present invention provides several methods for biological production of para-hydroxycinnamic acid (PHCA). The invention is also directed to the discovery of new fungi and bacteria that possess the ability to convert cinnamate to PHCA. The invention relates to developing of a new biocatalyst for conversion of glucose to PHCA by incorporation of the wild type PAL from the yeast Rhodotorula glutinis into E. coli underlining the ability of the wildtype PAL to convert tyrosine to PHCA. The invention is also directed to developing a new biocatalyst for conversion of glucose to PHCA by incorporation of the wildtype PAL from the yeast Rhodotorula glutinis plus the plant cytochrome P-450 and the cytochrome P-450 reductase into E. coli. In yet another embodiment, the present invention provides for the developing of a new biocatalyst through mutagenesis of the wild type yeast PAL which possesses enhanced tyrosine ammonia-lyase (TAL) activity. Excerpt(s): This invention relates to the field of molecular biology and microbiology. More specifically, this invention describes a new, genetically engineered biocatalyst possessing enhanced tyrosine ammonia-lyase activity. Phenylalanine ammonia-lyase (PAL) (EC 4.3.1.5) is widely distributed in plants (Koukol et al., J. Biol. Chem. 236:26922698 (1961)), fungi (Bandoni et al., Phytochemistry 7:205-207 (1968)), yeast (Ogata et al., Agric. Biol. Chem. 31:200-206 (1967)), and Streptomyces (Emes et al., Can. J. Biochem. 48:613-622 (1970)), but it has not been found in Escherichia coli or mammalian cells (Hanson and Havir In The Enzymes, 3.sup.rd ed.; Boyer, P., Ed.; Academic: New York, 1967; pp 75-167). PAL is the first enzyme of phenylpropanoid metabolism and catalyzes the removal of the (pro-3S)-hydrogen and --NH.sub.3.sup.+ from L-phenylalanine to form trans-cinnamic acid. In the presence of a P450 enzyme system, trans-cinnamic acid can be converted to para-hydroxycinnamic acid (PHCA) which serves as the common intermediate in plants for production of various secondary metabolites such as lignin and isoflavonoids. In microbes however, cinnamic acid and not the PHCA acts as the precursor for secondary metabolite formation. No cinnamate hydroxylase enzyme has so far been characterized from microbial sources. The PAL enzyme in plants is thought to be a regulatory enzyme in the biosynthesis of lignin, isoflavonoids and other phenylpropanoids (Hahlbrock et al., Annu. Rev. Plant Phys. Plant Mol. Biol. 40:347-369 (1989)). However, in the red yeast, Rhodotorula glutinis (Rhodosporidium toruloides), this lyase degrades phenylalanine as a catabolic function and the cinnamate formed by the action of this enzyme is converted to benzoate and other cellular materials. The gene sequence of PAL from various sources, including Rhodosporidium toruloides, has been determined and published (Edwards et al., Proc. Natl. Acad. Sci., USA 82:6731-6735 (1985); Cramer et al., Plant Mol. Biol. 12:367-383 (1989); Lois et al., EMBO J. 8:1641-1648 (1989); Minami et al., Eur. J. Biochem. 185:19-25 (1989); Anson et al., Gene 58:189-199 (1987); Rasmussen & Oerum, DNA Sequence, 1:207-211 (1991). The PAL genes from various sources have been over-expressed as active PAL enzyme in yeast, Escherichia coli and insect cell culture (Faulkner et al., Gene 143:13-20 (1994); Langer et al.,

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Biochemistry 36:10867-10871 (1997); McKegney et al., Phytochemistry 41:1259-1263 (1996)). PAL has received attention because of its potential usefulness in correcting the inborn error of metabolism phenylketonuria (Bourget et al., FEBS Lett. 180:5-8 (1985); U.S. Pat. No. 5,753,487), in altering tumor metabolism (Fritz et al. J. Biol. Chem. 251:4646-4650 (1976)), in quantitative analysis of serum phenylalanine (Koyama et al., Clin. Chim. Acta, 136:131-136 (1984)) and as a route for synthesizing L-phenylalanine from cinnamic acid (Yamada et al., Appl. Environ. Microbiol. 42:773 (1981), Hamilton et al., Trends in Biotechnol. 3:64-68 (1985) and Evans et al., Microbial Biotechnology 25:399405 (1987)). Web site: http://www.delphion.com/details?pn=US06521748__ •

pREM: a positive selection vector system for direct PCR cloning Inventor(s): Husain; Zaheed (Medford, MA), Malo; Madhu Sudan (Watertown, MA) Assignee(s): Synthegen Systems (Medford, MA) Patent Number: 6,544,782 Date filed: November 13, 2000 Abstract: The present invention describes the development of a positive selection vector based on regulatory element modulation, wherein such modulation is achieved via insertional reconstruction or destruction of a regulatory element controlling transcription, translation, DNA replication and termination. A positive selection cloning vector pREM5Tc has been developed based on insertional reconstruction of a regulatory element of a reporter gene. The vector pREM5Tc carries the tetracycline resistance reporter gene with no functional -35 region of its promoter, a regulatory element, thus resulting in no expression of the tetracycline resistance gene. Hence a host cell carrying the vector pREM5Tc is unable to produce the tetracycline resistance gene protein resulting in inhibition of its growth in presence of tetracycline. An E. coli consensus -35 region is recognized as 5'-TTGACA-3' and a primer used in polymerase chain reaction (PCR) carries at its 5' end the sequence 5'-TGTCAA-3', which is the complementary sequence of 5'-TTGACA-3'. The PCR-amplified DNA fragment is ligated to pREM5Tc thus reconstructing the functional promoter of the tetracycline resistance reporter gene. Subsequent transformation of a host cell with the recombinant vector (Carrying an insert DNA) results in production of the tetracycline resistance reporter gene protein that confers resistance to tetracycline thus allowing only the recombinants to grow in presence of tetracycline. The positive selection vector pREM5Tc greatly reduces, if not eliminates, the number of exonuclease-generated false positive clones. Excerpt(s): Ahrenhotz et al., "A conditional suicide system in Escherichia coli based on intracellular degradation of DNA" Appl. Environ. Microbiol. 60,3746-3751(1994). Altenbuchner et al., "Positive selection vectors based on palindromic DNA sequences" Methods Enzymol. 216, 457-466 (1992). Balbas et al., "Plasmid vector pBR322 and its special-purpose derivatives--a review" Gene 50, 3-40 (1986). Web site: http://www.delphion.com/details?pn=US06544782__

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PREPARATION AND USE OF FORMALIN-KILLED COLONIZATION-FACTORANTIGEN (CFA)-EXPRESSING E. COLI ORGANISMS FOR VACCINATION AGAINST ENTERIC INFECTION/DIARRHEA CAUSED BY ENTEROTOXIGENIC E. COLI BACTERIA IN HUMANS Inventor(s): Holmgren; Jan (Korvettgatan 1D, Vastra Frolunda S-421 74, SE), Svennerholm; Ann-Mari (Korvettgatan 1D, Vastra Frolunda S-421 74, SE) Assignee(s): none reported Patent Number: 6,558,678 Date filed: November 8, 1993 Abstract: Disclosed is a method of producing a vaccine composition against enteric infection caused by enterotoxigenic E. coli bacteria in humans. E. coli strains selected from different known strains each having the ability of expressing a certain type of colonization factor antigens are grown in a liquid culture medium. Finally formalinkilled E. coli strain having substantially preserved antigenic and hemagglutinating properties of said certain type of colonization factor antigens, is mixed with a pharmaceutically acceptable excipient and/or diluent. Further disclosed is a method of preventing an enteric infection caused by enterotoxigenic E. coli bacteria in humans, whereby a vaccine composition comprising inactivated E. coli strain is administered to a human being for the prevention of said infection. Excerpt(s): The present invention relates to the preparation and use of formalin-killed colonization-factor-antigen (CFA)-expressing E. coli organisms for vaccination against enteric infection/diarrhea caused by enterotoxigenic E. coli bacteria in humans. Specially, the invention relates to a method of producing a vaccine composition against enteric infection caused by enterotoxigenic E. coli bacteria in humans, and a method of preventing an enteric infection caused by enterotoxigenic E. coli bacteria in humans. Diarrhea caused by enterotoxinogenic Escherichia coli (ETEC) is an important health problem, particularly in developing countries and in travellers to these areas. In hospital- and clinic-based studies of acute diarrhea in developing countries ETEC has been identified in 10-50% of the cases, the average being ca 20% in children less than 5 years, and slightly higher in older age groups. Likewise, ETEC has been identified as the causative agent in at least one third to one half of cases of acute diarrhea among persons travelling from industrialized to developing countries. Web site: http://www.delphion.com/details?pn=US06558678__

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Process for producing microbial transglutaminase Inventor(s): Miwa; Tetsuya (Kawasaki, JP), Nakamura; Nami (Kawasaki, JP), Seguro; Katsuya (Kawasaki, JP), Yokoyama; Keiichi (Kawasaki, JP) Assignee(s): Ajinomoto Co., Inc. (Tokyo, JP) Patent Number: 6,538,122 Date filed: November 24, 1999 Abstract: Disclosed are a protein having a transglutaminase activity, which comprises a sequence ranging from serine residue at the second position to proline residue at the 331st position in an amino acid sequence represented by SEQ ID No. 1 wherein the Nterminal amino acid of the protein corresponds to serine residue at the second position of SEQ ID No. 1, a DNA encoding the protein, a transformant having the DNA, and a

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process for producing a protein having a transglutaminase activity, which comprises the steps of culturing the transformant in a medium. The protein can be produced in a large amount with the transformant using a host such as E. coli. Excerpt(s): The present invention relates to a protein having a transglutaminase activity, DNA which encodes for the protein, and a process for producing the protein. In particularly, the present invention relates to a process for producing a protein having a transglutaminase activity by a genetic engineering technique. Transglutaminase is an enzyme which catalyzes the acyl transfer reaction of a.gamma.-carboxyamido group in a peptide chain of a protein. When such an enzyme react with the protein, a reaction of an.epsilon.-(.gamma.-Glu)-Lys forming reaction or substitution reaction of Gln with Glu by the deamidation of Glu can occur. The transglutaminase is used for the production of gelled foods such as jellies, yogurts, cheeses, gelled cosmetics, etc. and also for improving the quality of meats [see Japanese Patent Publication for Opposition Purpose (hereinafter referred to as "J. P. KOKOKU") No. Hei 1-50382]. The transglutaminase is also used for the production of a material for microcapsules having a high thermal stability and a carrier for an immobilized enzyme. The transglutaminase is thus industrially very useful. Web site: http://www.delphion.com/details?pn=US06538122__ •

Process for the purification of human interleukin-1 receptor antagonist from recombinant E. coli Inventor(s): Sarubbi; Edoardo Giacomo (Fontenay sous Bois, FR), Soffientini; Adolfo (Sesto S. Giovanni, IT), Zanette; Dino (Pianzano Godega S. Urbano, IT) Assignee(s): Gruppo Lepetit S.p.A. (Milan, IT) Patent Number: 6,573,366 Date filed: May 9, 2000 Abstract: A process for purifying human Interleukin-1 receptor antagonist (IL-1ra), obtained by fermenting a strain of recombinant E. coli, which comprises: a) loading the mixture to be purified, which has been buffered at a pH value lower than 6.2 and optionally diluted to reduce its ionic strength at a low value, onto a cationic exchange matrix and eluting said matrix with an aqueous buffered solution having a pH value from about 7.5 to 9.0 and a low ionic strength; and b) applying the eluate from the cationic exchange step, containing the desired IL-1ra protein, directly onto an anionic exchange matrix and eluting with an aqueous buffered solution having a pH value within the above range 7.5 to 9.0 and an increased ionic strength. Excerpt(s): The present invention refers to a new purification process of the human Interleukin-1 receptor-antagonist (IL-1ra) obtained by fermenting a strain of recombinant E. coli. As known, the members of the interieukin-1 (IL-1) family are important mediators of inflammatory, and immune responses. Among these Interleukin-1.alpha. and.beta. (IL-1.alpha. and IL-1.beta.) behave as agonists on the IL-1 receptors, being responsible for the stimulation of a number of cellular activities related to inflammatory and immune responses. Although extremely important for mediating the immunological response against pathogens, overproduction of IL-1(i.e. IL-1.alpha. and IL-1.beta.) may in some cases lead to undesired pathogenic conditions. This is, for instance, the case of septic shock, graft versus host disease or autoimmune diseases, such as rheumatoid arthritis, insulin-dependent diabetes mellitus, multiple sclerosis and certain types of leukemia.

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Web site: http://www.delphion.com/details?pn=US06573366__ •

Recombinant DNA encoding a reverse transcriptase derived from moloney murine leukemia virus Inventor(s): Riggs; Michael G. (San Diego, CA), Sorensen; Matthew (Irvine, CA) Assignee(s): Gen-Probe Incorporated (San Diego, CA) Patent Number: 6,593,120 Date filed: September 15, 1999 Abstract: A recombinant plasmid for expression of Moloney Murine Leukemia Virus (MMLV)-derived reverse transcriptase in E. coli cells deficient in the expression of RNAse activity, a method for purification of the recombinant enzyme, and a purified recombinant reverse transcriptase for suitable use in cDNA and nucleic acid amplification procedures are disclosed. Excerpt(s): The invention relates to recombinant proteins, particularly to viral reverse transcriptase enzymes produced by recombinant DNA technology, and specifically relates to reverse transcriptase derived from Moloney Murine Leukemia virus (MMLV) that is expressed from recombinant DNA in a bacterial host cell and that includes multiple histidine residues. Retroviruses are a group of viruses whose genetic material consists of single-stranded RNA. Following adsorption and entry of retroviral RNA into the host cell, the viral RNA is used as a template for synthesis of a complementary DNA (CDNA) strand. The cDNA is then made double-stranded through the action of an enzyme having DNA polymerase activity; this double-stranded DNA integrates into the host genome. The RNA-directed DNA polymerase activity responsible for the synthesis of cDNA from the viral RNA template is commonly called reverse transcriptase ("RT"). A number of retroviruses have been implicated as the causative agents of various cancers, and other diseases. A retrovirus, human immunodeficiency virus-1 (HIV-1), is the causal agent of acquired immunodeficiency syndrome (AIDS). Also, reverse transcriptase enzymes have become important reagents in molecular biology because of their ability to make cDNA from almost any RNA template. Reverse transcriptase is commonly used to make nucleic acids for hybridization probes and to convert singlestranded RNA into a double-stranded DNA for subsequent cloning and expression. Web site: http://www.delphion.com/details?pn=US06593120__

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Recombinant vaccines against IBDV Inventor(s): Edelbaum; Orit (Western Galilee, IL), Gontmakher; Tanya (Western Galilee, IL), Khayat; Eli (Western Galilee, IL), Rogel; Arie (Western Galilee, IL), Sela; Ilan (Western Galilee, IL), Shachar; Yehoshua (Western Galilee, IL), Stram; Yehuda (Western Galilee, IL), Zanberg; Yehuda (Western Galilee, IL) Assignee(s): Meristem; Rahan (Rosh Hanikra, IL), Shafit (Shefaim, IL) Patent Number: 6,528,063 Date filed: January 4, 2000 Abstract: There is provided a stable vaccine for providing protection against disease having viral proteins transgenically expressed in plant cells. Also provided is a stable vaccine which provides protection against disease containing viral protein and coding

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sequences cloned into an E. coli expression system. A method of vaccination by transgenically expressing viral proteins capable of providing protection against disease into plant cells and administering the plant cells to an animal in need of vaccination is also provided. Also provided is a method of vaccination by cloning viral protein and coding sequences capable of providing protection against disease into an E. coli expression system and administering the E. coli into the animal in need of vaccination. Excerpt(s): The present invention relates to poultry vaccinations. More specifically, the present invention relates to vaccines against infectious bursal disease virus (IBDV). Vaccines which stimulate the mucosal immune system can be used to immunize, generally via an oral route, hosts against pathogens that are transmitted via the gastrointestinal, respiratory and urogenital tracts. These vaccines stimulate the mucosal immune system. See for example Shalaby, "Development of oral: vaccines to stimulate mucosal and systemic immunity: barriers and novel strategies" Clin Immunol Immunopathol 74(2):127-134, 1995; Mestecky et al, "Mucosal immunity and strategies for novel microbial vaccines" Acto Paediatr Jpn, 36(5):53744, 1994; U.S. Pat. Nos. 5,518,725 and 5,417,986. The mucosal immune system operates through the mucosa-related IgA and a complement of T cells with mucosa-specific regulatory or effector properties and provides for host defense at the mucosal surfaces. For a more complete review of the mucosal immune system see Strober and James, "The Mucosal Immune System" In Basic & Clinical Immunology 8th Edition eds Stites, Terr, Parslow, (Appleton & Lange, 1994), pgs 541-551, incorporated by reference in its entirety. Web site: http://www.delphion.com/details?pn=US06528063__ •

Reporter gene based method for the screening of anti-tuberculosis drugs by using essential and regulatory genes of mycobacteria as drug target Inventor(s): Agrawal; Pushpa (Chandigarh, IN), Khandrika; Lakshami Pathi (Chandigarh, IN), Soni; Vishal (Chandigarh, IN) Assignee(s): Council of Scientific and Industrial Research (New Delhi, IN) Patent Number: 6,645,505 Date filed: March 27, 2001 Abstract: The present invention relates to a method for making recombinant Saccharomyces cerevisiae. The method includes the steps of amplifying one or more whiB-like genes of Mycobacteria by polymerase chain reaction (PCR), cloning the amplified one or more whiB-like genes into a plasmid, transforming the clone into an E. coli using a first shuttle vector, amplifying the clone, introducing the amplified clone into a second shuttle vector, introducing said second shuttle vector into Saccharomyces cerevisiae. Excerpt(s): This invention relates to the development of a reporter gene based drug screening system against tuberculosis by using essential regulatory genes of Mycobacterium tuberculosis H37Rv as a target. Such regulatory genes are more particularly, the whiB genes of mycobacteria whose functions are essential for the survival and normal growth of mycobacteria. The Streptomycetes are dimorphic organisms. After reaching the late log phase of growth, the substrate mycelia differentiate into the aerial mycelia. The tip of the aerial mycelium then differentiates into a chain of spores. Each spore represents a single cell and is separated by a septum. In 1992, Davis and Chater (Davis, N. K. and Chater, K. F. 1992. Mol. Gen. Genet: 232: 352-358) reported that any mutation in the whiB gene of Streptomyces coelicolor A3(2)

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results into a non sporulating organism. These mutants were also white in colour since they had lost capability-to, produce deep reddish blue pigment which is a characteristic of the wild type strain of Streptomyces coelicolor A3(2). It was further confirmed that a fully functional whiB gene is essential for the sporulation of the Streptomyces coelicolor A3(2) and whiB gene may be a transcription activator. A whiB homologue was also reported from Streptoverticillium sps, Streptomyces aurofaciens and Rhodococcus opacus (Kormanec and Homerova, 1993 Nucl. Acid Res. 21 :2512; Seibert,V., Kourbatova, E. M., Golowela, L. M. and M. Schlomann. 1998. 180:3503-3508; Soliveri, J. E., Vijg nboom, E., Granozzi, C., Plaskitt, K. A. and K. F. Chater. 1993. J.Gen.Microbiol. 139:2569-2578). However, unexpectedly, the genome sequence of Mycobacterium tuberculosis H37Rv showed the presence of four genes that is whiBI/Rv3219-254 bp, whiB2/Rv3260c-269 bp, whiB3/Rv 3416-308 bp and whiB4/Rv368l c-302 bp whose deduced amino acid products were similar to the whiB gene of Streptomyces coelicolor A3(2). The amino acid sequences of whiB genes of M. tuberculosis H37Rv show 32-35 percent homology to the amino acid sequences of Streptomyces whiB genes. Although the homology is relatively low, the general property of the predicted protein remains conserved. General morphology of mycobacteria is bacillus, unlike the species of streptomycetes, which are filamentous. So far, sporulation of mycobacteria has not been reported. Therefore, the presence of whiB like genes, which controls the sporulation, in a non-sporulating organism is highly intriguing. The predicted amino acid sequence of whiB gene suggests that the whiB gene may code for a transcription activator. If that were so, then whiB genes would be a regulatory gene. However, so far it has not been reported that the whiB genes indeed code for a transcription activator, If the whiB genes are indeed a set of regulatory genes then the question is what kind of genes do they control? Recently, Gomez and Bishai (Gomez, J. E. and Bishai, W. R., 2000. Proc. Nati. Acad. Sci. 97: 8554-8559) have shown that a whiB2 homologue of Mycobacterium tuberculosis H37Rv is present in Mycobacterium smegmatis and is essential for its survival. Mycobacterium smegmatis is a fast growing and non-pathogenic organism. However no report or patent could be found related to the invention described in this application. The present invention describes that out of the four whiB genes originally described in the Mycobacterium tuberculosis H37Rv genome sequence, the whiB1/Rv 3219 is essential to the survival of the Mycobacterium bovis BCG and whiB3/Rv 3416 appears to control septa formation during cell division. The properties of these genes were not reported in the genome sequence of Mycobacterium tuberculosis H37Rv nor have they been published in the literature (Cole et al. Nature 1998. 393: 537-544.). Web site: http://www.delphion.com/details?pn=US06645505__ •

Synthetic HIV-2 envelope genes containing modifications that lead to optimized expression in bacteria Inventor(s): Casey; James M. (Gurnee, IL), Desai; Suresh M. (Libertyville, IL), Devare; Sushil G. (Northbrook, IL) Assignee(s): Abbott Laboratories (Abbott Park, IL) Patent Number: 6,538,127 Date filed: May 18, 1995 Abstract: The present invention provides a method of synthesizing genes encoding unique HIV-1 and HIV-2 envelope proteins and their fragments, thereby allowing overexpression of these proteins in E. coli. The HIV envelope proteins and their fragments have been expressed at high levels as individual proteins or in fusion with

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other proteins. The HIV envelope proteins thus expressed in E. coli can be effectively used for the detection of exposure to HIV as well as the discrimination of HIV-1 and HIV-2. Excerpt(s): The present invention relates to recombinant HIV (Human Immunodeficiency Virus) antigens. Recombinant antigens derived from the molecular cloning and expression in a heterologous expression system of the synthetic DNA sequences of the various HIV antigens can be used as reagents for the detection of antibodies and antigen in body fluids from individuals exposed to various HIV isolates. The nucleotide sequence of the proviral genome has been determined for several HIV isolates, including HIV-1 strains HTLV-III (Ratner et al., Nature (1985) 313:277); ARV-2 (Sanchez-Pescador et al., Science (1985) 227:484); LAV (Wain-Hobson et al., Cell (1985) 40:9); and CDC-451 (Desai et al., Proc. Natl. Acad. Sci. USA (1986) 83:8380). The nucleotide sequence of the HIV-2 ROD isolate was reported by Guyader et al. (Nature (1987) 326:662). It has been difficult to obtain expression in heterologous systems of some of the HIV proteins, such as the HIV-1 envelope antigen gp41. Several researchers have tried deleting the hydrophobic regions of the HIV-1 gp41 to increase expression levels. UK Patent Application GB 2188639 discloses an HTLV-III gag/env gene protein wherein the env fragment of the DNA sequence deleted codons corresponds to the first hydrophobic region of the gp41 protein. U.S. Pat. No. 4,753,873 discloses a peptide fragment that is encoded by a nucleotide sequence wherein the nucleotides coding for a first and second hydrophobic region of HTLV-III gp41 are deleted. Web site: http://www.delphion.com/details?pn=US06538127__ •

Thermostable phospholipase A1 mutants and a process for preparing the same Inventor(s): Rhee; Joon-Shick (Seoul, KR), Song; Jae-Kwang (Taejon, KR) Assignee(s): Korea Advanced Institute of Science and Technology (Taejon, KR) Patent Number: 6,610,524 Date filed: March 27, 2001 Abstract: The present invention provides thermostable phospholipase TA3 and TA13 which are mutants of phospholipase A1 involving the hydrolysis/synthesis of phospholipids, the mutated genes encoding the same, microorganisms transformed with recombinant expression vectors comprising the mutated genes and a process for preparing phospholipase A1 mutants therefrom. The process for preparing phospholipase A1 mutant of the invention comprises the steps of: culturing E. coli strain transformed with a recombinant expression vector comprising a gene coding for phospholipase A1 mutant derived from Serratia sp.; and, isolating and purifying phospholipase A1 mutant from the culture. Since phospholipase A1 mutants of the invention have been improved in terms of thermal stability and enzyme activity as well, they can be practically applied to various biological process, pharmaceutics, cosmetics and food industries. Excerpt(s): The present invention relates to phospholipase A1 mutants and a process for preparing the same, more specifically, to thermostable phospholipase TA3 and TA13 which are mutants of phospholipase A1 catalyzing the reaction of hydrolysis/synthesis of phospholipids, genes encoding the same, microorganisms transformed with recombinant expression vectors comprising the mutant genes and a process for preparing phospholipase A1 mutants therefrom. It has been known that: lysophospholipid not only plays a role in platelet aggregation, but also mediates

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physiological activity such as signal transduction in animal (see: Durieux and Lynch, Trends Pharmacol. Sci., 14: 249, 1993), and also functions as a plant hormone to prevent plants or fruits from over-ripening (see: U.S. Pat. No. 5,126,155). Since lysophospholipid is highly soluble in water and forms stable emulsion under various hydrogen ion concentrations and broad range of temperature and has stability in the presence of magnesium or calcium ion, it has been applied to many industrial uses as an emulsifier such as pharmaceutics, cosmetics and food processing. In biochemical pathway, lysophospholipid is formed via hydrolysis of phospholipid by phospholipase A1: that is, phospholipase A1 hydrolyzes 1-fatty acyl group (or fatty acyl group in the sn-1 position) of phospholipid to form lysophospholipid and fatty acid. The phospholipase A1 is an essential enzyme in the synthesis of phospholipids such as polyunsaturated fatty acids(PUFA) such as DHA or EPA. In physiological aspects, phospholipase A1 is related to human phospholipidosis caused by accumulation of phospholipid in lysosome due to the inhibition of phospholipase activity by cationic amphiphilic drug(CAD) (see: Reasor et al., Proc. Soc. Biol. Med., 212:297-304, 1996). Although phospholipase A1 has been isolated from a variety of sources such as mammals, snake toxins, bee toxins and microorganisms including Serratia sp. and Aspergillus sp., low stability of the enzymes hampered their application to biological processes. Web site: http://www.delphion.com/details?pn=US06610524__ •

Treatment of gastro-intestinal disorders Inventor(s): Borody; Thomas Julius (Five Dock, AU) Assignee(s): Gastro Services Pty Limited (Five Dock, AU) Patent Number: 6,645,530 Date filed: June 7, 1995 Abstract: A method of treating chronic disorders associated with the presence of abnormal microflora or an abnormal distribution of microflora in the gastrointestinal tract involves removing the host's existing enteric microflora and substitution of feces from a disease screener donor or composition comprising microorganism selected from the group consisting of Bacteroides and E. coli. Excerpt(s): The present invention relates to methods of treating diseases in mammals, in particular to the treatment of chronic disorders associated with the presence of abnormal or an abnormal distribution of microflora in the gastrointestinal tract. The invention also relates to pharmaceutical compositions suitable for the treatment of such disorders. There are large numbers of patients suffering from gastro-intestinal symptoms referrable to the lower small bowel and large bowel which to date have eluded explanation. These disorders include irritable bowel syndrome (IBS) or spastic colon, idiopathic ulcerative colitis, mucous colitis, collagenous colitis, Crohn's disease, inflammatory bowel disease in general, microscopic colitis, antibiotic-associated colitis, idiopathic or simple constipation, diverticular disease, and AIDS enteropathy. Pathophysiology of these disorders eludes logical explanation in spite of decades of research and millions of dollars of research funds. A common underlying factor shared by all these disorders observed by the present inventor is their onset following some extraneous invading infection. In all the disorders, the infection cannot be demonstrated due to our inability to detect infecting agents whose cultural characteristics are unknown to medical science. It is impractical to use long-term antibiotic therapy (with its associated complications) in such patients since cure is not obtained with its use. Furthermore, chronic gut infections with recognised, specific pathogens such as

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Clostridium difficile, Yersinia enterocolitica or Campylobacter jejuni/coli are not eradicated with antibiotics. Some previous attempts have been made to alter the enteric microflora in order to eradicate such chronic infections. These measures nevertheless indicate that alteration of bacterial flora may effect dramatic clinical improvement in conditions characterized by chronic, resistant enterocolitic infection. However there remain many chronic disorders of uncertain aetiology or causation, which are resistant to cure by current therapeutic techniques. Web site: http://www.delphion.com/details?pn=US06645530__ •

Use of thiol redox proteins for reducing protein intramolecular disulfide bonds, for improving the quality of cereal products, dough and baked goods and for inactivating snake, bee and scorpion toxins Inventor(s): Buchanan; Bob B. (Berkeley, CA), Kobrehel; Karoly (Montpellier, FR), Yee; Boihon C. (Walnut Creek, CA) Assignee(s): The Regents of the University of California (Oakland, CA) Patent Number: 6,583,271 Date filed: November 23, 1999 Abstract: Methods of reducing cystine containing animal and plant proteins, and improving dough and baked goods' characteristics is provided which includes the steps of mixing dough ingredients with a thiol redox protein to form a dough and baking the dough to form a baked good. The method of the present invention preferably uses reduced thioredoxin with wheat flour which imparts a stronger dough and higher loaf volumes. Methods for reducing snake, bee and scorpion toxin proteins with a thiol redox (SH) agent and thereby inactivating the protein or detoxifying the protein in an individual are also provided. Protease inhibitors, including the Kunitz and BowmanBirk trypsin inhibitors of soybean, were also reduced by the NADP/thioredoxin system (NADPH, thioredoxin, and NADP-thioredoxin reductase) from either E. coli or wheat germ. When reduced by thioredoxin, the Kunitz and Bowman-Birk soybean trypsin inhibitors lose their ability to inhibit trypsin. Moreover, the reduced form of the inhibitors showed increased susceptibility to heat and proteolysis by either subtilisin or a protease preparation from germinating wheat seeds. The 2S albumin of castor seed endosperm was reduced by thioredoxin from either wheat germ or E. coli. Thioredoxin was reduced by either NADPH and NADP-thioredoxin reductase or dithiothreitol. Analyses showed that thioredoxin actively reduced the intramolecular disulfides of the 2S large subunit, but was ineffective in reducing the intermolecular disulfides that connect the large to the small subunit. A novel cystine containing protein that inhibits pullulanase was isolated. The protein was reduced by thioredoxin and upon reduction its inhibitory activity was destroyed or greatly reduced. Excerpt(s): The present invention relates to the use of thiol redox proteins to reduce seed protein such as cereal proteins, enzyme inhibitor proteins, venom toxin proteins and the intramolecular disulfide bonds of certain other proteins. More particularly, the invention involves use of thioredoxin and glutaredoxin to reduce gliadins, glutenins, albumins and globulins to improve the characteristics of dough and baked goods and create new doughs and to reduce cystine containing proteins such as amylase and trypsin inhibitors so as to improve the quality of feed and cereal products. Additionally, the invention involves the isolation of a novel protein that inhibits pullulanase and the reduction of that novel protein by thiol redox proteins. The invention further involves the reduction by thioredoxin of 2S albumin proteins characteristic of oil-storing seeds.

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Also, in particularly the invention involves the use of reduced thiol redox agents to inactivate snake neurotoxins and certain insect and scorpion venom toxins in vitro and to treat the corresponding toxicities in individuals. This invention was made with government support under Grant Contract Nos. DCB 8825980 and DMB 88-15980 awarded by the National Science Foundation. The United States Government has certain rights in this invention. Thioredoxin h is also known to reductively activate cytosolic enzyme of carbohydrate metabolism, pyrophosphate fructose-6-P, 1-phosphotransferase or PFP (Kiss, F., et al. (1991), Arch. Biochem. Biophys. 287:337-340). Web site: http://www.delphion.com/details?pn=US06583271__

Patent Applications on E. coli As of December 2000, U.S. patent applications are open to public viewing.10 Applications are patent requests which have yet to be granted. (The process to achieve a patent can take several years.) The following patent applications have been filed since December 2000 relating to E. coli: •

Anti-idiotypic antibody against FimH adhesion of uropathogenic type I-fimbriated escherichia coli, compositions containing same and method for using same Inventor(s): Wu, Xue-Ru; (Staten Island, NY) Correspondence: Browdy And Neimark, P.L.L.C.; 624 Ninth Street, NW; Suite 300; Washington; DC; 20001-5303; US Patent Application Number: 20020028200 Date filed: May 10, 2001 Abstract: The present invention relates to an anti-idiotypic antibody or antigen-binding fragment against FimH adhesin of uropathogenic Type I-fimbriated Escherichia coli and an immunizing composition containing such an anti-idiotypic antibody or antigenbinding fragment thereof as an active immunizing component. The present invention also relates to a method for stimulating and enhancing the production of antibodies which recognize and bind to FimH of uropathogenic Type-I-fimbriated Escherichia coli, but not to FimH of non-uropathogenic Type I-fimbriated Escherichia coli. Excerpt(s): This application claims the benefit of priority from U.S. Provisional Application No. 60/204,572, filed May 16, 2000, the entire content of which is incorporated herein by reference. The present invention relates to an anti-idiotypic antibody and a composition containing same, such as an immunizing composition. Urinary tract infection (UTI) is one of the most common infectious diseases that primarily affect women of all ages. Nearly as many as 50% of all women experience at least one infection in the urinary tract during their lifetimes. Although as prevalent as the common cold, UTI causes far more discomfort and sends 10 million people annually in the United States alone to seek medical attention. Approximately 1.5 million of these visits are diagnosed as pyelonephritis (kidney infection), which is often so serious that hospitalization is required. In addition, approximately 20% of women experience frequent infections (on the order of three to six per year) after the initial episode of UTI, resulting in additional morbidity and lost productivity. It is estimated that five billion healthcare dollars are spent each year to treat UTIs.

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This has been a common practice outside the United States prior to December 2000.

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Web site: http://appft1.uspto.gov/netahtml/PTO/search-bool.html •

Bacterial strain of escherichia coli BKIIM B-3996 as the producer of L-threonine Inventor(s): Arsatiants, Raisa Alexandrovna; (Moscow, RU), Bachina, Tatyana Alexandrovna; (Moscow, RU), Belareva, Alla Valentinovna; (Moscow, RU), Chistoserdov, Andrei Jurievich; (Moskovskaya oblast, RU), Debabov, Vladimir Georgievich; (Moscow, RU), Gusyatiner, Mikhail Markovich; (Moscow, RU), Khurges, Evgeny Moiseevich; (Moscow, RU), Kozlov, Jury Ivanovich; (Moscow, RU), Livshits, Vitaly Arkadievich; (Moscow, RU), Plotnikova, Tatyana Grigorievna; (Moscow, RU), Pozdnyakova, Tamara Mikhailovna; (Moscow, RU), Shakalis, Irina Olegovna; (Moscow, RU), Sholin, Albert Fedorovich; (Moscow, RU), Sokolov, Alexandr Konstantinovich; (Moscow, RU), Tsygankov, Jury Dmitrievich; (Moscow, RU), Yankovsky, Nikolai Kazimirovich; (Moscow, RU), Zhdanova, Nelli Isaakovna; (Moscow, RU) Correspondence: Oblon Spivak Mcclelland Maier & Neustadt PC; Fourth Floor; 1755 Jefferson Davis Highway; Arlington; VA; 22202; US Patent Application Number: 20010049129 Date filed: July 13, 2001 Abstract: A bacterial strain of Escherichia coli BKIIM B-3996, a producer of L-threonine, containing a recombinant plasmid pVIC40 and deposited on Nov. 19, 1987 in the collection of microorganism cultures at the USSR Antibiotics Research Institute under Reg. No. 1867. Excerpt(s): The present invention relates generally to microbiological industry and more specifically it concerns a novel bacterial strain of Escherichia coli BKIIM. B-3996 as the producer of L-threonine. L-threonine is known to be an essential amino acid applicable as the component of diverse nutritive mixtures of medical use. Besides, L-threonine can be used as an additive to animals' fodder, as well as a reagent for the pharmaceutical and chemical industries and as a growth factor for microorganisms producing some other amino acids, such as L-lysine and L-homoserine. Known in the present state of the art as the L-threonine producing strains of microorganisms of a variety of species (e.g., Brevibacterium flavum, Serratia marcescens, Escherichia coli, and others). It is the mutating strains of E. coli whose cells contain hybrid plasmids caryying the genes of the threonine operon (U.S. Pat. Nos. 4,278,785; 4,321,325) that prove to be the most efficacious L-threonine producers, of which the most productive is Escherichia coli strain VNIIgenetika M-1 (U.S. Pat. No. 4,321,325), which contains multicopy plasmid pYN7 obtained in the base of vector pBR322 and incorporating the threonine operon of E. coli strain K12 resistant to alpha-amino-beta-hydroxyvaleric acid, an analogue of threonine. The genes of the threonine operon of plasmid pYN7 code a bifunctional enzyme, viz., aspartate-kinase-homoserinedehydrogenase, which is insensitive to inhibition with L-threonine. Said strain M-1 is capable of accumulating L-threonine till a concentration of 30 g/l for a 40-hour fermentation period in laboratory fermenters when cultivated under conditions of feeding a sugar-ammonia additive to the nutrient medium in response to a signal sent by the pH sensor. Web site: http://appft1.uspto.gov/netahtml/PTO/search-bool.html

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Base sequence of initiation site for efficient protein expression in escherichia coli Inventor(s): Pai, Emil F.; (Toronto, CA), Tang, Hailun; (North York, CA) Correspondence: Hailun Tang; 19 Heathview Avenue; North York; ON; M2k 2c2; CA Patent Application Number: 20030207444 Date filed: May 6, 2002 Abstract: Base sequences of initiation sites for efficient protein expression in escherichia coli having a common base sequence, the differences between them rendered mute due to looping and truncating of the base differences Excerpt(s): Worldwide genome sequencing efforts have identified many genes. The identification and production of proteins, for which the genes encode, is the work of Proteomics. Proteomics urgently requires a way to express these genes as proteins, so their structure can be analyzed and elucidated. Prokaryotic Escherichia coli, are most often used for protein expression because of their availability, robustness and well understood properties. Presently, many genes cannot be expressed using existing vectors. In some cases, this is due to the accidental occurrence of an initiation site inside the coding region of the gene destined for protein expression (internal initiation site), which interferes with the initiation site in the vector. In some cases the naturally occurring internal site is stronger than that of the vector, resulting in absent or reduced protein expression. However, in other cases the fault lies with the initiation site design of the vector. The initiation sites of vectors have been described as having three distinct, but connected functional sections: first, the Shine Dalgarno sequence (hereinafter referred to as the "SD"); next, the spacer; and finally, the start codon "ATG" or seldom, "GTG". The sequence of the SD is well known to the art and was first described by J. Shine and L. Dalgarno in their paper: The 3'-Terminal Sequence of Escherichia coli 16S Ribosomal RNA: Complementarity to Nonsense Triplets and Ribosome Binding Sites, Proc. Nat. Acad. Sci. USA, Vol. 71, No.4, pp. 1342-1346, April 1974. They reported that the 3'-terminal sequence of Escherichia coli 16S Ribosomal RNA is ACCUCCUUA.sub.OH. The complementary sequence for mRNA is: 5'-UAAGGAGGU, and this is referred to as the SD sequence (Chen 1994). The corresponding sequence in cDNA is: TAAGGAGGT, also referred to as the SD sequence, and herein referred to as the original SD sequence. Subsequently, this cDNA sequence has been truncated and modified in many ways and incorporated into protein expression vectors. For example, the vector pET-15b (Novagen) has an SD of: AGGAG; and the vector pCRT7/NT-TOPO (Invitrogen) has an SD of AGAAGGA. The preferred embodiment of the present invention incorporates an SD of AGGAGGT, which is a subset of the original cDNA SD sequence: TAAGGAGGT--leaving out only the first two bases T and A. Web site: http://appft1.uspto.gov/netahtml/PTO/search-bool.html

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Enterohemorrhagic escherichia coli vaccine Inventor(s): Finlay, Brett; (British Columbia, CA), Potter, Andrew A.; (Saskatchewan, CA) Correspondence: Robins & Pasternak Llp; Suite 200; 90 Middlefield Road; Menlo Park; CA; 94025; US Patent Application Number: 20020160020 Date filed: January 3, 2002

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Abstract: Compositions and methods for stimulating an immune response against a secreted enterohemorragic Escherichia coli (EHEC) antigen are disclosed. The compositions comprise EHEC cell culture supernatants. Excerpt(s): This application claims the benefit under 35 USC.sctn.119(e)(1) of provisional patent application serial no. 60/259,818, filed Jan. 4, 2001, which application is incorporated herein by reference in its entirety. The present invention relates to compositions and methods for eliciting an immune response in mammals against enterohemorragic Escherichia coli. In particular, the invention relates to the use of cell culture supernatants for treating and preventing enterohemorragic E. coli colonization of mammals. Enterohemorragic Escherichia coli (EHEC), also called Shiga toxin E. coli (STEC) and vertotoxigenic E. coli (VTEC) are pathogenic bacteria that cause diarrhea, hemorrhagic colitis, hemolytic uremic syndrome, kidney failure and death in humans. While many Shiga-like toxin-producing EHEC strains are capable of causing disease in humans, those of serotype O157:H7 cause the majority of human illness. This organism is able to colonize the large intestine of humans by a unique mechanism in which a number of virulence determinants are delivered to host cells via a type III secretion system, including the translocated Intimin receptor, Tir (DeVinney et al., Infect. Immun. (1999) 67:2389). In particular, these pathogens secrete virulence determinants EspA, EspB and EspD that enable delivery of Tir into intestinal cell membranes. Tir is integrated into the host cell membrane where it serves as the receptor for a bacterial outer membrane protein, Intimin. Tir-Intimin binding attaches EHEC to the intestinal cell surface and triggers actin cytoskeletal rearrangements beneath adherent EHEC that results in pedestal formation. EspA, EspB, Tir and Intimin are each essential for the successful colonization of the intestine by EHEC. Web site: http://appft1.uspto.gov/netahtml/PTO/search-bool.html •

ENZYMATIC PROCESS FOR THE PREPARATION OF CEPHALOSPORANIC 7$B(G)-(4-CARBOXYBUTANAMIDE) ACID BY MEANS OF THE MODIFIED ENZYME D-AMINOACID OXIDASE OF TRIGONOPSIS VARIABILIS PRODUCED IN ESCHERICHIA COLI Inventor(s): ALONSO PALACIOS, JORGE; (MADRID, ES), CORTES RUBIO, ESTRELLA; (MADRID, ES), DIEZ GARCIA, BRUNO; (LEON, ES), FUENTE, BARREDO; (LEON, ES), GARCIA LOPEZ, JOSE LUIS; (MADRID, ES), GUISAN SEIJAS, JOSE MANUEL; (MADRID, ES), MELLADO DURAN, ENCARNACION; (LEON, ES), SALTO MALDONADO, FRANCISO; (MADRID, ES) Correspondence: Baker & Botts; 30 Rockefeller Plaza; New York; NY; 10112 Patent Application Number: 20030119087 Date filed: July 15, 1999 Abstract: Enzymatic process for the preparation of cephalosporanic.sub.7?-(4carboxybutananude) acid by using the modified enzyme D-aminoacid oxidase of Trigonopsis variabilis produced in Escherichia coli. The process for the expression of the enzyme comprises: (I) isolating the DNA corresponding to gene which codes for the enzyme D-aminoacid oxidase; (II) removing the intron which is contained in said gene; (III) inserting the DNA fragment obtained into the plasmide which is capable of replication in Escherichia coli; (IV) fusing at the extremity 5' of the structural region of the gene a synthetic assembler which contains a nucleotide sequence which codes for six histidines; (V) transforming a strain of Escherichia coli with the resulting recombinant plasmide; (VI) cultivating the transformed cells of Escherichia coli; and (VII) recovering

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the enzyme D-aminoacid oxidase of the former cultivation operation through affinity chromatography. Excerpt(s): The present invention relates to an enzymatic process for the preparation of 7.beta.-(4-carboxybutanamide) cephalosporanic acid. More particularly, it describes a method for isolating the gene which codes for an enzyme with D-aminoacid oxidase activity by the use of recombinant DNA techniques, the cloning of said gene in a microorganism of the genus Escherichia, the modification of said enzyme by protein engineering techniques, the hyperproduction of said modified enzyme by fermentation in said microorganism and the extraction of the modified enzyme for preparation of 7.beta.-(4-carboxybutanamide) cephalosporanic acid. This acid is an intermediate compound for the preparation of 7-amino cephalosporanic acid, which in turn is a known intermediate for the preparation of a wide variety of antibacterial agents in the cephalosporins family. For the production of 7.beta.-(4-carboxybutanamide) cephalosporanic acid, also called glutaryl-7-aminocephalosporanic acid (hereinafter referred to as GL-7ACA), from cephalosporin C, the use of the enzyme D-aminoacid oxidase (hereinafter referred to as DAO) from various microorganisms such as Trigonopsis variabilis (Biochem. Biophys. Res. Commun. (1993) 31: 709), Rhodotorula gracilis (J. Biol. Chem. (1994) 269: 179) and Fusarium solani (J. Biochem. (1990) 108: 1063) is known. The production of DAO by the use of these microorganisms involves many disadvantages. For one thing, the level of production of DAO activity is very low, and, for another, other undesirable enzyme activities such as esterases and catalases are present together with said enzyme. The former break down GL-7ACA acid, reducing the yield and thus increasing the costs of the purification process. The latter destroy the hydrogen peroxide needed in the catalysis and necessitate the addition of this compound, which also increases the costs of the process and at the same time causes a loss in the activity of the enzyme, reducing its possibilities of re-use. In order to avoid said enzymatic contamination it is necessary to purify the DAO activity, which greatly increases the costs and difficulty of the enzymatic process for obtaining GL-7ACA from cephalosporin C. A process has recently been described for isolating the gene which codes for DAO in T. variabilis and expressing it in E. coli and in T. variabilis (Japanese Patent Application Laid-Open No. 71180/1988; European Patent Application No. 93202219.7, Publication No. 0583817A2). Moreover, the gene which codes for the DAO activity of F. solani has also been cloned and expressed in E. coli and Achremonium chrysogenum (Japanese Patent Application Laid-Open No. 2000181/1990; J. Biochem. (1990) 108: 1063; Bio/Technology (1991) 9: 188) and more recently the gene which codes for DAO in R. gracilis has been cloned and expressed in E. coli (Spanish Patent P9600906). Web site: http://appft1.uspto.gov/netahtml/PTO/search-bool.html •

L-arginine producing escherichia coli and method of producing L-arginine Inventor(s): Gusyatiner, Mikhail Markovich; (Moscow, RU), Leonova, Tatyana Viktorovna; (Moscow, RU), Ptitsyn, Leonid Romanovich; (Moscow, RU), Yampolskaya, Tatyana Abramovna; (Moscow, RU) Correspondence: Oblon Spivak Mcclelland Maier & Neustadt PC; Fourth Floor; 1755 Jefferson Davis Highway; Arlington; VA; 22202; US Patent Application Number: 20020034793 Date filed: June 22, 2001

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Abstract: Arginine can be efficiently produced by cultivating Escherichia coli which has an ability to produce arginine and an ability to utilize acetate in a culture medium to produce and accumulate arginine in the medium, and collecting arginine from the medium. Excerpt(s): The present invention relates to L-arginine producing Escherichia coli and a method of producing L-arginine by fermentation using Escherichia coli. L-arginine is an industrially useful amino acid as ingredients of liver function promoting agents, amino acid transfusions, comprehensive amino acid preparations and the like. It is known that some mutants of Escherichia coli resistant to analogs of arginine and pyrimidines produce arginine (Pierard A. and Glansdorf N., Mol. Gen. Genet., 118, 235, 1972. and Glansdorf N., Biosynthesis of arginine and polyamines. In "E. coli and Salm. thyphimurium, 1996). Additionally, the methods for producing arginine using mutants of E. coli resistant to some other drugs or recombinant strain of E. coli into which a gene encoding an enzyme of arginine biosynthetic pathway is introduced are known. It is also known that E. coli can not effectively utilize acetate as carbon source. Web site: http://appft1.uspto.gov/netahtml/PTO/search-bool.html •

Method for detecting Escherichia coli Inventor(s): Chung, Te-Yu; (Hsinshu, TW), Liu, Lu-Yieng; (Hsinshu, TW), Terng, HarnJing; (Hsinchu, TW) Correspondence: Fish & Richardson PC; 225 Franklin ST; Boston; MA; 02110; US Patent Application Number: 20030113731 Date filed: December 19, 2001 Abstract: Specific nucleic acid sequences, e.g., SEQ ID NOs: 1-8, for detecting Escherichia coli. Also disclosed is a method of detecting Escherichia coli. The method includes providing a sample having a nucleic acid from an unknown microorganism; amplifying the nucleic acid with an upstream primer containing SEQ ID NO: 1 or 3 and a downstream primer containing SEQ ID NO: 2 or 4, each primer being 18-40 nucleotides in length; and detecting an amplification product. Detection of the amplification product, e.g., using SEQ ID NO: 5, 6, 7, or 8 as a probe, indicates the presence of Escherichia Coli. Excerpt(s): Traditional methods of detecting microorganisms rely on time-consuming growth in culture media, followed by isolation and biochemical or serological identification. The entire process usually takes 24-48 hours. Many methods for rapid detection of microorganisms have recently been developed, including miniaturized biochemical analyses, antibody- and DNA-based tests, and modified conventional assays. Detection of the microorganism Escherichia coli in water and food has been considered as an indicator of the possible presence of enteric pathogens. Indeed, certain E. coli strains are pathogenic themselves. Rapid and accurate identification of E. coli is therefore important for public health. The present invention relates to specific nucleic acid sequences for detecting Escherichia coli. Web site: http://appft1.uspto.gov/netahtml/PTO/search-bool.html

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Method for isolation and identification of Escherichia coli 0157:H7 and plating media for said process Inventor(s): Restaino, Lawrence; (Elburn, IL) Correspondence: Marshall A. Burmeister; P.O. Box 824; Chicago; IL; 60690; US Patent Application Number: 20020142366 Date filed: March 18, 2002 Abstract: An isolation plating medium for use in processes for the presumptive identification of Escherichia coli 0157:H7 from a sample that also contains other strains of Escherichia coli. The plating medium comprises at least one carbohydrate that Escherichia coli 0157:H7 is incapable of fermenting, but other strains of Escherichia coli do ferment said carbohydrate, a pH indicator dye that changes the color of the plating medium to a first color when the pH of the medium changes, a chromogenic substrate that reacts to beta-galactosidase to form a precipitate in the plating medium of a second color which contrasts with the first color. Both Escherichia coli 0157:H7 and the other strains of Escherichia coli are beta-galactosidase producers during metabolism, whereby a microorganism which ferments the carbohydrate but does not produce betagalactosidase will produce colonies in the plating medium of the first color, Escherichia coli 0157:H7 which does not ferment the carbohydrate but produces beta-galactosidase will produce colonies in the plating medium of the second color, and the other strains of Escherichia coli which ferment the carbohydrate medium and produce betagalactosidase will produce colonies in the plating medium of a third color which is the color that results from the mixing of the first and second colors, and a sufficient mass of an agent to solidify the mixture. The invention also includes processes of using the plating medium to identify and enumerate Escherichia coli 0157:H7 and other microorganisms. Excerpt(s): The present application is a continuation of application Ser. No. 09/553,964, filed Apr. 21, 2000, by Lawrence Restaino entitled METHOD FOR ISOLATION OF ESCHERICHIA COLI 0157:H7 AND PLATING MEDIA FOR SAID PROCESS, and application Ser. No. 09/553,964, is a continuation of application Ser. No. 09/178,019, filed Oct. 23, 1998, now U.S. Pat. No. 6,087,156, and application Ser. No. 09/178,019 is a continuation of application Ser. No. 08/714,690, filed Sep. 16, 1996 now abandoned. The present invention relates to a process for isolating Escherichia coli 0157:H7 from other strains of Escherichia coli and other microorganisms, and to a solid plating media suitable for use in that process. Escherichia coli 0157:H7 has been recognized as an important human pathogen. Studies have shown that it is principally transmitted through food, Escherichia coli 0157:H7: Epidemiology, Pathogenesis, and Methods for Detection in Food, Nisha V. Padhye and Michael P. Doyle--Journal of Food Protection, Vol. 55, No. 7, Pages 555-565 (July 1992). There is thus a need for a rapid diagnostic test for the presence of Escherichia coli 0157:H7 in food in order to prevent the spread of Escherichia coli 0157:H7 through the food supply. Pradhye and Doyle, supra, survey methods of detection of Escherichia coli 0157:H7. A stable characteristic of Escherichia coli 0157:H7 is that it will not ferment sorbitol within 24 hours whereas other strains of Escherichia coli will produce fermentation in sorbitol under incubation temperatures within 24 hours, and this characteristic has been used in processes for the isolation of Escherichia coli 0157:H7 from other enterics. Since there are microorganisms other than Escherichia coli 0157:H7 that do not ferment sorbitol, including some strains of Escherichia coli, this characteristic is not sufficiently specific to serve as an identifying test for Escherichia coli 0157:H7.

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Web site: http://appft1.uspto.gov/netahtml/PTO/search-bool.html •

Novel Escherichia coli having accession no PTA 1579 and its use to produce polyhydroxybutyrate Inventor(s): Mahishi, L.H.; (Maharashtra, IN), Ramchander, T.V.N.; (Maharashtra, IN), Rawal, Shuban Kishen; (Maharashtra, IN), Tripathi, G.; (Maharashtra, IN) Correspondence: Baker & Botts; 30 Rockefeller Plaza; New York; NY; 10112 Patent Application Number: 20020146785 Date filed: January 29, 2001 Abstract: The present invention provides a novel genetically modified Escherichia coli JM109 bearing accession number PTA 1579, containing the gene coding for poly-betahydroxybutyrate synthesis and a method of using this bacterium to produce poly-betahydroxybutyrate to the extent of 60% or more of the cell weight. Excerpt(s): The present invention relates to the field of recombinant deoxyribonucleic acid (DNA) technology. Specifically, the invention relates to identification of the genes responsible for poly-beta-hydroxybutyrate biosynthesis pathway from Streptomyces aureofaciens NRRL 2209, creation of a plasmid vector carrying the said gene and expression of this gene in Escherichia coli designated as NCIM 5128 and bearing ATCC Accession No. PTA 1579, which is used for synthesis of polyhydroxybutyrate in recoverable amounts of at least 60% of dry bacterial cell mass. Lemoigne in 1926 discovered the presence of PHB (poly-beta-hydroxybutyrate) in Bacillus. This has been reported to be present in a multitude of other bacterial genera, including Azotobacter, Alcaligenes, Psuedonomas, Rhizobium, Chromatium, Acinetobacter, Rhodospirillum and some species of cyanobacteria. It is also reported to be present in certain actinomycetes in very minute quantities. PHB is synthesized and stored by these microorganisms essentially as an energy source under stress conditions. PHB, a homopolymer of D-(-)-3-hydroxybutyrate, has properties comparable to synthetic polymers like polypropylene. PHB is commercially produced by fermentation technology using Alcaligenes eutrophus (Ralstonia eutropha) and is marketed under the brand name Biopol. In the present global environment awareness, as against synthetic polymers which are persistent by nature, PHB is bestowed with the property of biodegradability. Besides being used in packaging industry, PHB has also been used as a source of chiral centers for the organic synthesis of certain antibiotics, in drug delivery and bone replacement applications. The biosynthesis of PHB has been studied extensively in Alcaligenes eutrophus, Rhodospirullum rubrum, Pseudomonas species and Azotobacter beijerinckii.beta.-ketothiolase, the first enzyme in the pathway and coded for by the phaA gene, first catalyzes the reversible condensation of two acetyl coenzyme A (CoA) molecules to acetoacetyl-CoA. Acetoacetyl-CoA is then reduced to D-(-)-3-hydroxybutyryl-CoA by NADPH dependent acetoacetyl-CoA reductase which is coded for by phaB gene. D-(-)-3-hydroxybutyryl-CoA monomer is then polymerized to PHB by PHB synthase coded for by the phaC gene. PHB in the bacterial cell accumulates as cytoplasmic inclusions when growth of the bacteria in culture is limited by a nutrient other than a carbon source. It may be oxygen deprivation, nitrogen deprivation, phosphate limitation, sulfate limitation and magnesium limitation. Once the limiting conditions are relaxed, PHB is metabolized down to preinduction levels. It has been shown that both.beta.-ketothiolase and acetoacetyl CoA reductase activities increase in response to PHB-stimulating limitation conditions. Some of the U.S. Patents covering production and extraction of PHB from microorganisms include the following: U.S. Pat.

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No. 4,786,598 to Lafferty et al. discloses a two-stage fermentation process where PHB is produced using Alcaligenes latus, U.S. Pat. No. 4,705,604 to Vanlautem et al. discloses using 1,2 dichloroethane to simultaneously remove water from the bacterial suspension by azeotropic distillation and extract PHB from the cells, U.S. Pat. No. 4,477,654 to Holmes et al discloses limiting the nitrogen nutrient source to microbiologically accumulate 3-hydroxybutyrate polymers, U.S. Pat. No. 4,433,053 discloses a fermenting process for PHB accumulation using A. eutrophus where a nutrient required for growth is limited, U.S. Pat. No. 4,336,334 to Powell et al. shows a microbiological process for producing PHB using Methylobacterium organophilum, U.S. Pat. No. 4,358,583 to Walker et al. discloses extracting PHB by first flocculating the cells by heat or pH treatment then extracting with a suitable solvent, U.S. Pat. No. 4,138,291 to Lafferty discloses bacterial strains assimilating various carbon sources and converting them to PHB, U.S. Pat. No. 5,518,907 to Dennis discloses Cloning and expression in Escherichia coli of the Alcaligenes eutrophus H16 poly-beta-hydroxybutyrate biosynthetic pathway, U.S. Pat. No. 5,798,235 to Peoples, et. al., gene encoding bacterial acetoacetyl Co-A reductase and U.S. Pat. No. 5,650,555 to Somerville et. al. discloses transgenic plants producing polyhydroxyalkanoates. U.S. Pat. No. 5,512,456 to Dennis discloses method for the improved production and recovery of poly-beta-hydroxybutyrate from transformed Escherichia coli, U.S. Pat. No. 5,250,430 discloses Polyhydroxyalkanoate polymerase from Zoogloea ramigera. Web site: http://appft1.uspto.gov/netahtml/PTO/search-bool.html •

Novel proteins in enteroaggregative escherichia coli (EAEC) useful for diagnosis and therapy of EAEC infections Inventor(s): Nataro, James; (Owings Mills, MD) Correspondence: Sughrue Mion, Pllc; 2100 Pennsylvania Avenue, N.W.; Washington; DC; 20037; US Patent Application Number: 20030180315 Date filed: December 2, 2002 Abstract: Novel proteins and their corresponding nucleotide sequences in enteroaggregative Escherichia coli (EAEC) are provided. In particular, Aap and the five gene cluster (aat) of the AA probe region of the pAA plasmid of EAEC 042 have been identified, sequenced, and further characterized. The use of these novel proteins and their corresponding nucleotide sequences for diagnosis, therapy, and prevention of EAEC infections is also provided. Excerpt(s): This non-provisional application claims priority under 35 U.S.C.sctn.120 to provisional applications U.S. Serial Nos. 60/334,425 and 60/398,775, filed Nov. 30, 2001 and Jul. 26, 2002, respectively, the contents of which are incorporated herein by reference in their entirety. The present invention relates generally to novel proteins and genes in enteroaggregative Escherichia coli (EAEC), and more particularly, to the use of these proteins and their corresponding nucleotide sequences for diagnosis, therapy, and prevention of EAEC infections. Enteroaggregative Escherichia coli (EAEC) is an emerging enteric pathogen associated with sporadic, endemic, and epidemic diarrheal illnesses in individuals of all ages in both developing and industrialized countries. (Nataro et al., Emerg Infect Dis 4:251-261 (1998); Nataro et al., Clin Microbiol Rev. 11:142-201 (1998); Okeke et al., Lancet Infect Dis 1:304-313 (2001)). The pathogenesis of EAEC infection includes strong adherence to the intestinal mucosa, most likely to both the small and the large intestines, followed by secretion of one or more enterotoxins that

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induce cytopathic effects in intestinal epithelial cells. (Nataro et al., Infect Immun 64:4761-4768 (1996); Eslava et al., Escherichia coli. Infect Immun 66:3155-3163 (1998); Czeczulin et al., Infect Immun 67:2692-2699 (1999)). Adherence of EAEC to the intestinal mucosa is characterized by the presence of a thick aggregating biofilm, which may favor the persistence of this organism in the human intestine. (Nataro et al., Clin Microbiol Rev. 11: 142-201 (1998); Tzipori et al., Infect Immun 60:5302-5306 (1992)). In addition, EAEC may induce intestinal inflammation, which can precipitate growth failure even in the absence of diarrhea. (Steiner et al., J Infect Dis 177:88-96 (1998)). Web site: http://appft1.uspto.gov/netahtml/PTO/search-bool.html •

Nucleotide sequence of Escherichia coli pathogenicity islands Inventor(s): Choi, Gil H.; (Rockville, MD), Dillon, Patrick J.; (Carlsbad, CA), Welch, Rodney A.; (Madison, WI) Correspondence: Human Genome Sciences Inc; 9410 Key West Avenue; Rockville; MD; 20850 Patent Application Number: 20020072595 Date filed: September 20, 2001 Abstract: The present invention relates to novel genes located in two chromosomal regions within uropathogenic E. coli that are associated with virulence. These chromosomal regions are known as pathogenicity islands (PAIs). In particular, the present application discloses 142 sequenced fragments (Contigs) of DNA from two pools of cosmids covering pathogenicity islands PAI IV and PAI V located on the chromosome of the uropathogenic Escherichia coli J96. Further disclosed are 351 predicted protein-coding open reading frames within the sequenced fragments. Excerpt(s): This application is a divisional of, and claims benefit under 35 U.S.C.sctn. 120 to copending U.S. patent application Ser. No. 08/976,259, filed Nov. 21, 1997, which in turn claims benefit under 35 U.S.C.sctn. 119(e) to U.S. Provisional Application Nos. 60/061,953, filed on Oct. 14, 1997, and 60/031,626, filed on Nov. 22, 1996. Claimed priority documents are hereby incorporated by reference in its entirety. The present invention relates to novel genes located in two chromosomal regions within E. coli that are associated with virulence. These chromosomal regions are known as pathogenicity islands (PAIs). Escherichia coli (E. coli) is a normal inhabitant of the intestine of humans and various animals. Pathogenic E. coli strains are able to cause infections of the intestine (intestinal E. coli strains) and of other organs such as the urinary tract (uropathogenic E. coli) or the brain (extraintestinal E. coli). Intestinal pathogenic E. coli are a well established and leading cause of severe infantile diarrhea in the developing world. Additionally, cases of newborn meningitis and sepsis have been attributed to E. coli pathogens. Web site: http://appft1.uspto.gov/netahtml/PTO/search-bool.html

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Plasmid to be used in chromosome recombination of escherichia coli Inventor(s): Kino, Kuniki; (Chiba-shi, JP), Purukawa, Satoru; (Chesterfield, MO), Takano, Junichi; (Cape Girardeau, MO) Correspondence: Fitzpatrick Cella Harper & Scinto; 30 Rockefeller Plaza; New York; NY; 10112; US Patent Application Number: 20030049846 Date filed: October 4, 2002 Abstract: A temperature-sensitive plasmid which is capable of autonomous replication in Escherichia coli K-12 at 10-30.degree. C., but, at a temperature of 33.degree. C. or more, is incapable of autonomous replication in Escherichia coli K-12 or is distributed unhomogeneously upon the cell division of Escherichia coli K-12, thereby not to be stably carried within cells of Escherichia coli K-12 under said temperature, and which is incapable of autonomous replication in a microorganism belonging to the genus Escherichia other than Escherichia coli K-12 or is distributed unhomogeneously upon cell division of said microorganism at any temperature, thereby not to be stably carried within cells of said microorganism. Excerpt(s): The present invention relates to a plasmid to be used for integrating genes into a microorganism belonging to the genus Escherichia other than Escherichia coli K12, a method for integrating the genes into the chromosome, a recombinant strain constructed according to the method, and a method for producing useful substances by using the recombinant strain. When a microorganism engineered to intracellularly carry a plasmid that expresses a specific gene is utilized for the production of a useful substance, over-expression of the gene and instability of the plasmid often cause problems. To solve the problems, modifications of genes on a chromosome are carried out as an effective method. Methods involving mutagenic treatments have long been carried out as a chromosomal engineering technique in Escherichia coli. This method is directed to the selection of a desired mutant strain from randomly mutated strains, and requires a great deal of work. In addition, deliberate or rational manipulation is almost impossible. On the other hand, P1 transduction using P1 phage is known to be the most versatile technique to deliberately and rationally manipulate the chromosome of Escherichia coli [Zinder, N. D. and Lederberg J., J. Bacteriol., 64, 679 (1952)]. Web site: http://appft1.uspto.gov/netahtml/PTO/search-bool.html

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Polymorphic loci that differentiate escherichia coli 0157:H7 from other strains Inventor(s): Tarr, Phillip I.; (Seattle, WA) Correspondence: Knobbe Martens Olson & Bear Llp; 620 Newport Center Drive; Sixteenth Floor; Newport Beach; CA; 92660; US Patent Application Number: 20020150902 Date filed: June 5, 2001 Abstract: The present invention relates generally to the field of microbiology and food sciences. More particularly, the inventor has discovered several polynucleotide sequences encoding the gnd gene and corresponding 6-phosphogluconate dehydrogenase (6-PGD) proteins from different strains of Escherichia Coli and polymorphic sequences therein. Novel biotechnological tools, diagnostics, and food screening techniques are provided.

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Excerpt(s): This application is a continuation of International Application number PCT/US99/29149 and claims priority to said International Application and U.S. Provisional Patent Application No. 60/111,493, filed Dec. 8, 1998, both of which are hereby expressly incorporated by reference in their entireties. The present invention relates generally to the field of microbiology and food sciences. More particularly, the inventor has discovered the gnd gene and corresponding 6-phosphogluconate dehydrogenase (6-PGD) protein from fourteen different strains of Escherichia coli and polymorphic sequences therein. Novel biotechnological tools, diagnostics, and food screening techniques are provided. Escherichia coli O157:H7 is an exceptionally virulent food borne, human pathogen that causes a spectrum of illness, including asymptomatic and post-symptomatic carriage, mild diarrhea, bloody diarrhea/hemorrhagic colitis, and the postdiarrheal, potentially lethal, hemolytic uremic syndrome (HUS). (Wilson et al., J Infect Dis, 174:1021-1027 (1996); (Karch et al., J Clin Microbiol, 33:1602-1605 (1995); (Rodrigue et al., J Infect Dis, 172:1122-1125 (1995); (Riley et al., N Engl J Med, 308:681-685 (1983); (Karmali et al., Lancet, 1:619-620 (1983); Neill et al., Arch Intern Med, 145:22152217 (1985); Neill et al., Pediatrics, 80:37-40 (1987); and Tarr et al., J Infect Dis, 162:553556 (1990)). While other E. coli strains are considered in some contexts to be pathogens, the excessive pathogenicity of E. coli O157:H7 is a well recognized distinguishing feature. Web site: http://appft1.uspto.gov/netahtml/PTO/search-bool.html •

Recombinant bioluminescent bacteria Escherichia coli DH5@/pSodaLux (EBHJ1) [KCTC 10098BP] for monitoring oxidative stress Inventor(s): Gu, Man Bock; (Kwangju, KR), Lee, Hyun Joo; (Seoul, KR) Correspondence: Pennie And Edmonds; 1155 Avenue OF The Americas; New York; NY; 100362711 Patent Application Number: 20030134348 Date filed: November 5, 2002 Excerpt(s): The present invention relates to recombinant bioluminescent bacteria Escherichia coli DH5@/pSodaLux (EBHJ1) [KCTC 10098BP] for monitoring oxidative stress. Recombinant vector pSodaLux including the SOD (superoxide dismutase) promoter gene is introduced to Escherichia coli to produce transformed recombinant bioluminescent bacteria Escherichia coli DH5@/pSodaLux (EBHJ1). These bacteria are sensitive in monitoring oxidative stress, which is fatal to living organisms. Most of the conventional bioluminescent bacteria emit certain lights at normal conditions. When they are exposed to toxic materials, the light emission reduces due to death or decrease of metabolism [Microtox.TM., Microbics Corp., Carlsbad, Calif., U.S.]. Oxidative stress is very harmful to microorganisms, plants and animals. It is because the reactive oxygen free radical transforms cell membranes, proteins and nucleic acids. Also in humans, it causes retrogressive diseases like Alzheimer's disease, diabetes and fatal diseases like cancers. Therefore, monitoring of natural and synthetic toxic materials causing oxidative stress is highly required. Web site: http://appft1.uspto.gov/netahtml/PTO/search-bool.html

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Secretion of T cell receptor fragments from recombinant escherichia coli cells Inventor(s): Ward, Elizabeth S.; (Dallas, TX) Correspondence: David L. Parker; Fulbright & Jaworski L.L.P.; Suite 2400; 600 Congress Avenue; Austin; TX; 78701; US Patent Application Number: 20030082814 Date filed: June 4, 2002 Abstract: Variable domain murine T-cell receptor genes have been isolated and used to construct cloning and expression vectors. V.sub.alpha., V.sub.beta., and single chain V.sub.alpha.-V.sub.beta. fragments have been expressed as secreted domains in Escherichia coli using the vectors. The domains are secreted into the culture supernatant in milligram quantities. The single domains and the single chain T-cell receptors are folded into.beta.-pleated sheet structures similar to those of immunoglobulin variable domains. The secreted fragments may be useful for immunization to generate anti-clonotypic antibodies, in vaccination or for high resolution structural studies. The genes encoding these domains may also serve as templates for in vitro mutagenesis and improvement of affinities of the TCR fragments for their interaction with cognate peptide-MHC complexes. Excerpt(s): This is a continuation-in-part of U.S. patent application Ser. No. 07/822,302, filed Jan. 17, 1992, pending. The invention relates to cloning vectors useful for the expression of T-cell variable domains, to bacterial cells transformed by the vectors and to methods of producing T-cell variable domains in a prokaryotic host cell, either as single domains or as single chain heterodimers. The production of single or heterodimeric T-cell receptor variable domains is of interest for purposes of studying Tcell receptor interaction with antigens and possibly developing approaches to therapies for autoimmune diseases and cancer. An important goal of molecular biology is a detailed understanding at the molecular level of the binding of T-cell receptors to cognate peptide-major histocompatibility complexes. This will be a step in the development, for example, of immunotherapy for T-cell mediated autoimmune disease. Despite this interest and the potential applications arising from the study of T-cell receptor domains, no methods are available for the production of only single T-cell receptor domains, nor has expression and secretion in prokaryotic hosts been successful. Web site: http://appft1.uspto.gov/netahtml/PTO/search-bool.html

Keeping Current In order to stay informed about patents and patent applications dealing with E. coli, you can access the U.S. Patent Office archive via the Internet at the following Web address: http://www.uspto.gov/patft/index.html. You will see two broad options: (1) Issued Patent, and (2) Published Applications. To see a list of issued patents, perform the following steps: Under “Issued Patents,” click “Quick Search.” Then, type “E. coli” (or synonyms) into the “Term 1” box. After clicking on the search button, scroll down to see the various patents which have been granted to date on E. coli. You can also use this procedure to view pending patent applications concerning E. coli. Simply go back to http://www.uspto.gov/patft/index.html. Select “Quick Search” under “Published Applications.” Then proceed with the steps listed above.

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CHAPTER 7. BOOKS ON E. COLI Overview This chapter provides bibliographic book references relating to E. coli. In addition to online booksellers such as www.amazon.com and www.bn.com, excellent sources for book titles on E. coli include the Combined Health Information Database and the National Library of Medicine. Your local medical library also may have these titles available for loan.

Book Summaries: Federal Agencies The Combined Health Information Database collects various book abstracts from a variety of healthcare institutions and federal agencies. To access these summaries, go directly to the following hyperlink: http://chid.nih.gov/detail/detail.html. You will need to use the “Detailed Search” option. To find book summaries, use the drop boxes at the bottom of the search page where “You may refine your search by.” Select the dates and language you prefer. For the format option, select “Monograph/Book.” Now type “E. coli” (or synonyms) into the “For these words:” box. You should check back periodically with this database which is updated every three months. The following is a typical result when searching for books on E. coli: •

Escherichia Coli 0157:H7: Diarrheal Illness and Hemolytic-Uremic Syndrome Source: Research Triangle Park, NC: Glaxo Wellcome Inc. 1995. 24 p. Contact: Available from Glaxo Wellcome Educational Resource Center. 5 Moore Drive, Research Triangle Park, NC 27709. (800) 824-2896. PRICE: Single copy free; available to health care professionals only. Order Number GVL231. Summary: This monograph familiarizes readers with diarrheal illness and hemolyticuremic syndrome (HUS), associated with Escherichia coli 0157:H7. Topics include the epidemiology of illness caused by enterohemorrhagic E. coli, including HUS; methods for isolating and identifying this pathogen and establishing the diagnosis of HUS; treatment for individuals with enterohemorrhagic E. coli-induced illness; and methods for preventing this illness. One section provides information for patients about E. coli 0157:H7. The monograph concludes with a multiple-choice self-test, with which readers

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can qualify for continuing medical education (CME) credits. 2 figures. 3 tables. 32 references. (AA-M).

Book Summaries: Online Booksellers Commercial Internet-based booksellers, such as Amazon.com and Barnes&Noble.com, offer summaries which have been supplied by each title’s publisher. Some summaries also include customer reviews. Your local bookseller may have access to in-house and commercial databases that index all published books (e.g. Books in Print). IMPORTANT NOTE: Online booksellers typically produce search results for medical and non-medical books. When searching for “E. coli” at online booksellers’ Web sites, you may discover nonmedical books that use the generic term “E. coli” (or a synonym) in their titles. The following is indicative of the results you might find when searching for “E. coli” (sorted alphabetically by title; follow the hyperlink to view more details at Amazon.com): •

Coliforms and E. coli (Rsc Special Publications, 191) by D Kay, C Fricker (1997); ISBN: 0854047719; http://www.amazon.com/exec/obidos/ASIN/0854047719/icongroupinterna

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E. coli by Chris Hayhurst (2003); ISBN: 0823942015; http://www.amazon.com/exec/obidos/ASIN/0823942015/icongroupinterna

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E. coli 0157: The True Story of a Mother's Battle With a Killer Microbe by Mary Heersink (1996); ISBN: 0882821431; http://www.amazon.com/exec/obidos/ASIN/0882821431/icongroupinterna

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E. coli Gene Expression Protocols by Peter E. Vaillancourt (Editor); ISBN: 1588290085; http://www.amazon.com/exec/obidos/ASIN/1588290085/icongroupinterna

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E. coli in Motion by Howard C. Berg (2003); ISBN: 0387008888; http://www.amazon.com/exec/obidos/ASIN/0387008888/icongroupinterna

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E. coli Plasmid Vectors: Methods and Applications (Methods in Molecular Biology (Clifton, N.J.), V. 235.) by Nicola Casali (Editor), Andrew Preston (Editor); ISBN: 1588291510; http://www.amazon.com/exec/obidos/ASIN/1588291510/icongroupinterna

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E. coli: A Practical Approach to the Organism and Its Control in Foods by J. Sainsbury, et al (1998); ISBN: 0751404624; http://www.amazon.com/exec/obidos/ASIN/0751404624/icongroupinterna

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E. coli: Shiga Toxin Methods and Protocols (Methods in Molecular Medicine, 73) by Dana Philpott (Editor), et al (2002); ISBN: 0896039390; http://www.amazon.com/exec/obidos/ASIN/0896039390/icongroupinterna

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Escherichia Coli 0157: H7 and Other Verotoxigenic E. coli in Foods by Workshop on Methods to Isolate Escherichia Coli O157:H7 and Other Vero, et al; ISBN: 0921317395; http://www.amazon.com/exec/obidos/ASIN/0921317395/icongroupinterna

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Escherichia coli and man by E. Mary Cooke; ISBN: 0443010544; http://www.amazon.com/exec/obidos/ASIN/0443010544/icongroupinterna

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Escherichia coli and Other Shiga Toxin-Producing E. coli by Alison D. O'Brien, Alison D. O'Brien (Editor); ISBN: 1555811299; http://www.amazon.com/exec/obidos/ASIN/1555811299/icongroupinterna

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Fecal coliform and Escherichia coli bacteria in the St. Croix National Scenic Riverway, summer 1999 (SuDoc I 19.42/4:00-4214/CORR.) by Sharon E. Kroening; ISBN: B000114KRM; http://www.amazon.com/exec/obidos/ASIN/B000114KRM/icongroupinterna

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Functional Studies of E. coli Ribosomes and Characterization of Mini Open Reading Frames (Comprehensive Summaries of Uppsala Dissertations, 524) by Vildan Dincbas (2000); ISBN: 9155446922; http://www.amazon.com/exec/obidos/ASIN/9155446922/icongroupinterna

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Gene cloning in organisms other than E. coli; ISBN: 0387111174; http://www.amazon.com/exec/obidos/ASIN/0387111174/icongroupinterna

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Gene Function: E. coli by Robert E. Glass; ISBN: 0520046544; http://www.amazon.com/exec/obidos/ASIN/0520046544/icongroupinterna

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No E. coli in My Kitchen: A Home Food Safety Handbook by R. D. Ann Lachney (2001); ISBN: 0965995739; http://www.amazon.com/exec/obidos/ASIN/0965995739/icongroupinterna

•

Phosphorus and E. coli in the Fanno and Bronson Creek subbasins of the Tualatin River basin, Oregon, during summer low-flow conditions, 1996 (SuDoc I 19.42/4:004062) by Kathleen A. McCarthy; ISBN: B000113CNK; http://www.amazon.com/exec/obidos/ASIN/B000113CNK/icongroupinterna

•

Regulation of Gene Expression in Escherichia Coli by E. C. C. Lin (Editor), A. Simon Lynch (Editor); ISBN: 0412102919; http://www.amazon.com/exec/obidos/ASIN/0412102919/icongroupinterna

•

The Official Patient's Sourcebook on E. coli: A Revised and Updated Directory for the Internet Age by Icon Health Publications (2002); ISBN: 0597830517; http://www.amazon.com/exec/obidos/ASIN/0597830517/icongroupinterna

•

When Food Kills: Bse, E. coli and Disaster Science by T. Hugh Pennington, Hugh Pennington (2003); ISBN: 0198525176; http://www.amazon.com/exec/obidos/ASIN/0198525176/icongroupinterna

The National Library of Medicine Book Index The National Library of Medicine at the National Institutes of Health has a massive database of books published on healthcare and biomedicine. Go to the following Internet site, http://locatorplus.gov/, and then select “Search LOCATORplus.” Once you are in the search area, simply type “E. coli” (or synonyms) into the search box, and select “books only.” From there, results can be sorted by publication date, author, or relevance. The following was recently catalogued by the National Library of Medicine:11

11

In addition to LOCATORPlus, in collaboration with authors and publishers, the National Center for Biotechnology Information (NCBI) is currently adapting biomedical books for the Web. The books may be accessed in two ways: (1) by searching directly using any search term or phrase (in the same way as the bibliographic database PubMed), or (2) by following the links to PubMed abstracts. Each PubMed abstract has a "Books" button that displays a facsimile of the abstract in which some phrases are hypertext links. These phrases are also found in the books available at NCBI. Click on hyperlinked results in the list of books in which the phrase is found. Currently, the majority of the links are between the books and PubMed. In the future, more links will be created between the books and other types of information, such as gene and protein sequences and macromolecular structures. See http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=Books.

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•

A piezoelectric crystal immunosensor for E. coli Author: Theegala, Chandra S., Southern-Univ., USA.; Year: 2003; Warrendale, PA: SAE International, 1997

•

E. coli: a practical approach to the organism and its control in foods Author: Bell, C.,; Year: 2000; London; New York: Blackie Academic; Professional, 1998; ISBN: 0751404616

•

Escherichia coli O157:H7 in ground beef: review of a draft risk assessment Author: Institute of Medicine (U.S.). Committee on the Review of the USDA E. coli O157:H7 Farm-to-Table Process Risk Assessment.; Year: 1983; Washington, D.C.: National Academies Press, c2002; ISBN: 0309086272 http://www.amazon.com/exec/obidos/ASIN/0309086272/icongroupinterna

•

Gene function: E. coli and its heritable elements Author: Glass, Robert E.,; Year: 1982; London: Croom Helm, c1982; ISBN: 0709900813

•

Investigation of space flight effects on Escherichia coli growth Author: Klaus, David M., BioServe Space Technologies, University of Colorado, USA.; Year: 2003; Warrendale, PA: SAE International, 1994

•

On the antibody response to E. coli antigens in immunized rabbits and in children with pyelonephritis Author: Holmgren, Jan.; Year: 1969; Göteborg: [s.n.], 1969

•

RNA, cloned human DNA and E. coli sequences, codon usage, and restriction enzyme recognition sequences.; Year: 1998; Oxford; New York: IRL Press, c1990

•

Studies of the infection of E. coli B with the bacteriophage T2. [Translated by S. J. Charleston. Author: Hedén, Carl-Göran.; Year: 1949; Copenhagen, Munksgaard] 1951

•

Studies on the antibody response to E. coli O antigen and the protective and serological properties of the antibodies with special reference to avidity Author: Ahlstedt, Staffan.; Year: 1973; Göteborg: [s.n.], 1973

•

The effect of sulfadiazine on the metabolism of E. coli. Author: Frances, Saul,; Year: 1956; New York, 1952

•

The relationship of acoustical energy to the lethal effects of ultrasonic vibrations on E. coli [by] John P. Horton and M. P. Horwood. Author: Horton, John P.; Year: 1952; [Cambridge, Dept. of Civil and Sanitary Engineering, Massachusetts Institute of Technology, 1951?]

•

The relationship of time, temperature and concentration on the germicidal effects of ultrasonic waves on E. coli [by] M. P. Horwood, J. P. Horton and V. A. Minch. Author: Massachusetts Institute of Technology. Dept. of Civil and Sanitary Engineering.; Year: 1951; Cambridge [1949?]

•

The role of enteropathogenic E. coli in infantile diarrhoea: aspects on bacteriology, epidemiology, and therapy Author: Thorén, Anders.; Year: 1987; Malmö: [s.n.]; Stockholm, Sweden: Distributed by Almqvist; Wiksell Periodical Co., 1983

•

Third International E. coli Genome Meeting [microform]: November 4-8, 1994, Marine Biological Laboratory, Woods Hole, Massachusetts: [abstracts of talks]. Author: United States. Dept. of Energy.; Year: 1989; [Woods Hole, Mass.?: The Laboratory?, 1994?]

•

tRNA, cloned human DNA and E. coli sequences, histone genes and restriction enzyme recognition sequences.; Year: 1994; Oxford; New York: IRL Press, c1989

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Chapters on E. coli In order to find chapters that specifically relate to E. coli, an excellent source of abstracts is the Combined Health Information Database. You will need to limit your search to book chapters and E. coli using the “Detailed Search” option. Go to the following hyperlink: http://chid.nih.gov/detail/detail.html. To find book chapters, use the drop boxes at the bottom of the search page where “You may refine your search by.” Select the dates and language you prefer, and the format option “Book Chapter.” Type “E. coli” (or synonyms) into the “For these words:” box. The following is a typical result when searching for book chapters on E. coli: •

Escherichia Coli O157:H7 Gastroenteritis and the Hemolytic Uremic Syndrome: An Emerging Infectious Disease Source: in Coggins, C.H., ed. Annual Review of Medicine: Selected Topics in the Clinical Sciences, Volume 50. Palo Alto, CA: Annual Reviews. 1999. p. 355-367. Contact: Available from Annual Reviews. 4139 El Camino Way, P.O. Box 10139, Palo Alto, CA 94303-0139. (650) 493-4400. E-mail: [email protected]. Website: www.AnnualReviews.org. PRICE: $60.00 plus shipping and handling. ISBN: 0824305507. Summary: Escherichia coli O157:H7 is an increasingly common cause of a variety of illnesses, including blood diarrhea and the hemolytic uremic syndrome (HUS). This emerging infectious agent was first identified in 1982 and has been isolated with increasing frequency since then. This article reviews the epidemiology, clinical spectrum, diagnosis, treatment, and prevention of infections with E. coli O157:H7. Infection with E. coli O157:H7 can be entirely asymptomatic or can present with a wide variety of clinical findings, including watery diarrhea, bloody diarrhea, HUS, thrombotic thrombocytopenic purpura (TTP), and death. The illness usually resolves after 1 week with no obvious sequelae; however, 5 to 10 percent of children with E. coli O157:H7 infection will develop HUS. HUS consists of the triad of microangiopathic hemolytic anemia, thrombocytopenia, and oliguric renal failure. Antimicrobial agents have no proven value in the treatment of E. coli O157:H7 infections. Antimotility agents should not be given to patients with bloody diarrhea or suspected E. coli O157:H7 infection, as these drugs may increase the risk of HUS in these patients. Treatment of HUS is supportive, with particular attention to the management of fluids and electrolytes. With meticulous care, the mortality rate for HUS is approximately 4 percent. 1 figure. 62 references. (AA-M).

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CHAPTER 8. MULTIMEDIA ON E. COLI Overview In this chapter, we show you how to keep current on multimedia sources of information on E. coli. We start with sources that have been summarized by federal agencies, and then show you how to find bibliographic information catalogued by the National Library of Medicine.

Video Recordings An excellent source of multimedia information on E. coli is the Combined Health Information Database. You will need to limit your search to “Videorecording” and “E. coli” using the “Detailed Search” option. Go directly to the following hyperlink: http://chid.nih.gov/detail/detail.html. To find video productions, use the drop boxes at the bottom of the search page where “You may refine your search by.” Select the dates and language you prefer, and the format option “Videorecording (videotape, videocassette, etc.).” Type “E. coli” (or synonyms) into the “For these words:” box. The following is a typical result when searching for video recordings on E. coli: •

Raw Terror: E. coli Bacteria Source: Princeton, NJ: Films for the Humanities and Sciences. 1997. (videocassette). Contact: Available from Films for the Humanities and Sciences. P.O. Box 2053, Princeton, NJ 08543-2053. (800) 257-5126 or (609) 275-1400. Fax (609) 275-3767. E-mail: [email protected]. Website: www.films.com. PRICE: $129.00 to purchase; $75.00 for rental; plus shipping and handling. Order number BXA6998. Summary: Eleven year old Damion Heersink nearly died after eating meat tainted with Escherichia coli:0157. This program details his battle to survive and documents the procedures that saved him. Doctors explain how E. coli bacteria produce hemolytic uremic syndrome, a condition that releases toxins into the bloodstream and can cause kidney failure. The program shows how kidney dialysis and a risky plasma exchange remove toxins from his system and reports on the use of two emergency surgeries to extract fluids from around his heart and to repair a hole in his intestine through which

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bacteria are escaping. Permanent lung and kidney damage are shown as two possible results of exposure to E. coli. (AA-M). •

E. coli: Case of the Mysterious Microbe Source: Princeton, NJ: Films for the Humanities and Sciences. 1998. (videocassette). Contact: Available from Films for the Humanities and Sciences. P.O. Box 2053, Princeton, NJ 08543-2053. (800) 257-5126 or (609) 275-1400. Fax (609) 275-3767. E-mail: [email protected]. Website: www.films.com. PRICE: $129.00 to purchase; $75.00 for rental; plus shipping and handling. Order number BXA7945. Summary: In this factual case study, revelers at a Burns Day celebration in Scotland become ill. When Escherichia coli is suspected, health officials try to discover its source. They and researchers move cautiously from one possible cause to the next: the food served, the water drunk, the improper handling of the food. When none of the investigations prove conclusive, suspicions mount that the microbe was probably passed on by someone sitting at the table where people became ill. During the program, researchers working on the case trace the evolution of the deadly 0157 E. coli strain from animals to ancient humans and make connections between E. coli and diseases such as flu and tuberculosis. The program is presented in a documentary style, with all involved parties contributing to solving the mystery. The viewer is taken back to the scene and follows along each trail of inquiry. The program covers the symptoms of E. coli poisoning, the most striking of which is severe abdominal pain and diarrhea. For children, the infection can result in kidney failure, and for older people it can be fatal. Although the mystery of this particular outbreak was never solved, the program packs a powerful message about the toxicity of E. coli: 0157 and the importance of appropriate food handling techniques.

Bibliography: Multimedia on E. coli The National Library of Medicine is a rich source of information on healthcare-related multimedia productions including slides, computer software, and databases. To access the multimedia database, go to the following Web site: http://locatorplus.gov/. Select “Search LOCATORplus.” Once in the search area, simply type in E. coli (or synonyms). Then, in the option box provided below the search box, select “Audiovisuals and Computer Files.” From there, you can choose to sort results by publication date, author, or relevance. The following multimedia has been indexed on E. coli: •

E. coli [videorecording]: case of the mysterious microbe Source: a presentation of Films for the Humanities & Sciences; a Border Television co-production with the EBS Trust; Year: 1998; Format: Videorecording; Princeton, N.J.: Films for the Humanities & Sciences, c1998

•

E. coli 0157 [sound recording]: H7: where's the beef?: recorded at DDW 1995 in San Diego Source: AGA; Year: 1995; Format: Sound recording; [United States]: American Gastroenterological Association, [1995?]

•

E. coli O157:H7 [videorecording]: what the clinical microbiologist should know Source: Centers for Disease Control and Prevention; produced by Television Services, Training and Media Development Branch, Division of Media and Training Services, Public Health P; Year: 1994; Format: Videorecording; Alanta, GA: The Centers, [1994]

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•

E. coli omega protein [videorecording]: an enzyme which breaks and rejoins the DNA backbone Source: University of Texas Cancer Center M. D. Anderson Hospital and Tumor Institute: [produced by] MDA-TV; Year: 1977; Format: Videorecording; Houston: The Center, 1977

•

F. A. detection of enteropathogenic Escherichia coli [motion picture] Source: National Communicable Disease Center, Laboratory Program; [made by] National Medical Audiovisual Center; Year: 1967; Format: Motion picture; [Atlanta]: The Center: [for loan by National Medical Audiovisual Center; Washington: for sale by National Audiovisual Center], 1967

•

Function of methyladenine in e. coli DNA [videorecording] Source: University of Texas System Cancer Center M. D. Anderson Hospital and Tumor Institute; Year: 1976; Format: Videorecording; Houston: The Institute, 1976

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Of mice and men and E. coli [sound recording] Source: Great Atlantic Radio Conspiracy; Year: 1977; Format: Sound recording; [Baltimore]: Great Atlantic Radio Conspiracy, [1977]

•

Sequences in human, bovine, and E. coli tryptophanyl tRNA synthetases [videorecording] Source: University of Texas System Cancer Center M. D. Anderson Hospital and Tumor Institute; Year: 1976; Format: Videorecording; Houston: The Institute, 1976

•

The Functional expression of cloned eukaryotic DNA in escherichia coli [videorecording] Source: University of Texas Health Science Center at Houston, Graduate School of Biomedical Sciences; [produced by] MDA-TV; Year: 1977; Format: Videorecording; Houston: The Center, 1977

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CHAPTER 9. PERIODICALS AND NEWS ON E. COLI Overview In this chapter, we suggest a number of news sources and present various periodicals that cover E. coli.

News Services and Press Releases One of the simplest ways of tracking press releases on E. coli is to search the news wires. In the following sample of sources, we will briefly describe how to access each service. These services only post recent news intended for public viewing. PR Newswire To access the PR Newswire archive, simply go to http://www.prnewswire.com/. Select your country. Type “E. coli” (or synonyms) into the search box. You will automatically receive information on relevant news releases posted within the last 30 days. The search results are shown by order of relevance. Reuters Health The Reuters’ Medical News and Health eLine databases can be very useful in exploring news archives relating to E. coli. While some of the listed articles are free to view, others are available for purchase for a nominal fee. To access this archive, go to http://www.reutershealth.com/en/index.html and search by “E. coli” (or synonyms). The following was recently listed in this archive for E. coli: •

Carbonating cow manure kills E. coli bacteria Source: Reuters Health eLine Date: April 28, 2000

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Plasma exchange may be effective for hemolytic uremic syndrome/TTP due to E. coli infection Source: Reuters Medical News Date: October 15, 1999

•

Canadian collaboration to test intranasal E. coli vaccine Source: Reuters Medical News Date: March 11, 1999 The NIH

Within MEDLINEplus, the NIH has made an agreement with the New York Times Syndicate, the AP News Service, and Reuters to deliver news that can be browsed by the public. Search news releases at http://www.nlm.nih.gov/medlineplus/alphanews_a.html. MEDLINEplus allows you to browse across an alphabetical index. Or you can search by date at the following Web page: http://www.nlm.nih.gov/medlineplus/newsbydate.html. Often, news items are indexed by MEDLINEplus within its search engine. Business Wire Business Wire is similar to PR Newswire. To access this archive, simply go to http://www.businesswire.com/. You can scan the news by industry category or company name. Market Wire Market Wire is more focused on technology than the other wires. To browse the latest press releases by topic, such as alternative medicine, biotechnology, fitness, healthcare, legal, nutrition, and pharmaceuticals, access Market Wire’s Medical/Health channel at http://www.marketwire.com/mw/release_index?channel=MedicalHealth. Or simply go to Market Wire’s home page at http://www.marketwire.com/mw/home, type “E. coli” (or synonyms) into the search box, and click on “Search News.” As this service is technology oriented, you may wish to use it when searching for press releases covering diagnostic procedures or tests. Search Engines Medical news is also available in the news sections of commercial Internet search engines. See the health news page at Yahoo (http://dir.yahoo.com/Health/News_and_Media/), or you can use this Web site’s general news search page at http://news.yahoo.com/. Type in “E. coli” (or synonyms). If you know the name of a company that is relevant to E. coli, you can go to any stock trading Web site (such as http://www.etrade.com/) and search for the company name there. News items across various news sources are reported on indicated hyperlinks. Google offers a similar service at http://news.google.com/.

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BBC Covering news from a more European perspective, the British Broadcasting Corporation (BBC) allows the public free access to their news archive located at http://www.bbc.co.uk/. Search by “E. coli” (or synonyms).

Academic Periodicals covering E. coli Numerous periodicals are currently indexed within the National Library of Medicine’s PubMed database that are known to publish articles relating to E. coli. In addition to these sources, you can search for articles covering E. coli that have been published by any of the periodicals listed in previous chapters. To find the latest studies published, go to http://www.ncbi.nlm.nih.gov/pubmed, type the name of the periodical into the search box, and click “Go.” If you want complete details about the historical contents of a journal, you can also visit the following Web site: http://www.ncbi.nlm.nih.gov/entrez/jrbrowser.cgi. Here, type in the name of the journal or its abbreviation, and you will receive an index of published articles. At http://locatorplus.gov/, you can retrieve more indexing information on medical periodicals (e.g. the name of the publisher). Select the button “Search LOCATORplus.” Then type in the name of the journal and select the advanced search option “Journal Title Search.”

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CHAPTER 10. RESEARCHING MEDICATIONS Overview While a number of hard copy or CD-ROM resources are available for researching medications, a more flexible method is to use Internet-based databases. Broadly speaking, there are two sources of information on approved medications: public sources and private sources. We will emphasize free-to-use public sources.

U.S. Pharmacopeia Because of historical investments by various organizations and the emergence of the Internet, it has become rather simple to learn about the medications recommended for E. coli. One such source is the United States Pharmacopeia. In 1820, eleven physicians met in Washington, D.C. to establish the first compendium of standard drugs for the United States. They called this compendium the U.S. Pharmacopeia (USP). Today, the USP is a non-profit organization consisting of 800 volunteer scientists, eleven elected officials, and 400 representatives of state associations and colleges of medicine and pharmacy. The USP is located in Rockville, Maryland, and its home page is located at http://www.usp.org/. The USP currently provides standards for over 3,700 medications. The resulting USP DI Advice for the Patient can be accessed through the National Library of Medicine of the National Institutes of Health. The database is partially derived from lists of federally approved medications in the Food and Drug Administration’s (FDA) Drug Approvals database, located at http://www.fda.gov/cder/da/da.htm. While the FDA database is rather large and difficult to navigate, the Phamacopeia is both user-friendly and free to use. It covers more than 9,000 prescription and over-the-counter medications. To access this database, simply type the following hyperlink into your Web browser: http://www.nlm.nih.gov/medlineplus/druginformation.html. To view examples of a given medication (brand names, category, description, preparation, proper use, precautions, side effects, etc.), simply follow the hyperlinks indicated within the United States Pharmacopeia (USP).

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Commercial Databases In addition to the medications listed in the USP above, a number of commercial sites are available by subscription to physicians and their institutions. Or, you may be able to access these sources from your local medical library.

Mosby’s Drug Consult Mosby’s Drug Consult database (also available on CD-ROM and book format) covers 45,000 drug products including generics and international brands. It provides prescribing information, drug interactions, and patient information. Subscription information is available at the following hyperlink: http://www.mosbysdrugconsult.com/.

PDRhealth The PDRhealth database is a free-to-use, drug information search engine that has been written for the public in layman’s terms. It contains FDA-approved drug information adapted from the Physicians’ Desk Reference (PDR) database. PDRhealth can be searched by brand name, generic name, or indication. It features multiple drug interactions reports. Search PDRhealth at http://www.pdrhealth.com/drug_info/index.html. Other Web Sites Drugs.com (www.drugs.com) reproduces the information in the Pharmacopeia as well as commercial information. You may also want to consider the Web site of the Medical Letter, Inc. (http://www.medletter.com/) which allows users to download articles on various drugs and therapeutics for a nominal fee.

Researching Orphan Drugs Although the list of orphan drugs is revised on a daily basis, you can quickly research orphan drugs that might be applicable to E. coli by using the database managed by the National Organization for Rare Disorders, Inc. (NORD), at http://www.rarediseases.org/. Scroll down the page, and on the left toolbar, click on “Orphan Drug Designation Database.” On this page (http://www.rarediseases.org/search/noddsearch.html), type “E. coli” (or synonyms) into the search box, and click “Submit Query.” When you receive your results, note that not all of the drugs may be relevant, as some may have been withdrawn from orphan status. Write down or print out the name of each drug and the relevant contact information. From there, visit the Pharmacopeia Web site and type the name of each orphan drug into the search box at http://www.nlm.nih.gov/medlineplus/druginformation.html. You may need to contact the sponsor or NORD for further information. NORD conducts “early access programs for investigational new drugs (IND) under the Food and Drug Administration’s (FDA’s) approval ‘Treatment INDs’ programs which allow for a limited number of individuals to receive investigational drugs before FDA marketing approval.” If the orphan product about which you are seeking information is approved for

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marketing, information on side effects can be found on the product’s label. If the product is not approved, you may need to contact the sponsor. The following is a list of orphan drugs currently listed in the NORD Orphan Drug Designation Database for E. coli: •

humanized monoclonal antibody against Shiga-like t (trade name: NONE Assigned) http://www.rarediseases.org/nord/search/nodd_full?code=1169

•

Humanized monoclonal antibody against Shiga-like t http://www.rarediseases.org/nord/search/nodd_full?code=1221

•

Synsorb Pk http://www.rarediseases.org/nord/search/nodd_full?code=299

If you have any questions about a medical treatment, the FDA may have an office near you. Look for their number in the blue pages of the phone book. You can also contact the FDA through its toll-free number, 1-888-INFO-FDA (1-888-463-6332), or on the World Wide Web at www.fda.gov.

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APPENDICES

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APPENDIX A. PHYSICIAN RESOURCES Overview In this chapter, we focus on databases and Internet-based guidelines and information resources created or written for a professional audience.

NIH Guidelines Commonly referred to as “clinical” or “professional” guidelines, the National Institutes of Health publish physician guidelines for the most common diseases. Publications are available at the following by relevant Institute12: •

Office of the Director (OD); guidelines consolidated across agencies available at http://www.nih.gov/health/consumer/conkey.htm

•

National Institute of General Medical Sciences (NIGMS); fact sheets available at http://www.nigms.nih.gov/news/facts/

•

National Library of Medicine (NLM); extensive encyclopedia (A.D.A.M., Inc.) with guidelines: http://www.nlm.nih.gov/medlineplus/healthtopics.html

•

National Cancer Institute (NCI); guidelines available at http://www.cancer.gov/cancerinfo/list.aspx?viewid=5f35036e-5497-4d86-8c2c714a9f7c8d25

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National Eye Institute (NEI); guidelines available at http://www.nei.nih.gov/order/index.htm

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National Heart, Lung, and Blood Institute (NHLBI); guidelines available at http://www.nhlbi.nih.gov/guidelines/index.htm

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National Human Genome Research Institute (NHGRI); research available at http://www.genome.gov/page.cfm?pageID=10000375

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National Institute on Aging (NIA); guidelines available at http://www.nia.nih.gov/health/

12

These publications are typically written by one or more of the various NIH Institutes.

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•

National Institute on Alcohol Abuse and Alcoholism (NIAAA); guidelines available at http://www.niaaa.nih.gov/publications/publications.htm

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National Institute of Allergy and Infectious Diseases (NIAID); guidelines available at http://www.niaid.nih.gov/publications/

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National Institute of Arthritis and Musculoskeletal and Skin Diseases (NIAMS); fact sheets and guidelines available at http://www.niams.nih.gov/hi/index.htm

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National Institute of Child Health and Human Development (NICHD); guidelines available at http://www.nichd.nih.gov/publications/pubskey.cfm

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National Institute on Deafness and Other Communication Disorders (NIDCD); fact sheets and guidelines at http://www.nidcd.nih.gov/health/

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National Institute of Dental and Craniofacial Research (NIDCR); guidelines available at http://www.nidr.nih.gov/health/

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National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK); guidelines available at http://www.niddk.nih.gov/health/health.htm

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National Institute on Drug Abuse (NIDA); guidelines available at http://www.nida.nih.gov/DrugAbuse.html

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National Institute of Environmental Health Sciences (NIEHS); environmental health information available at http://www.niehs.nih.gov/external/facts.htm

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National Institute of Mental Health (NIMH); guidelines available at http://www.nimh.nih.gov/practitioners/index.cfm

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National Institute of Neurological Disorders and Stroke (NINDS); neurological disorder information pages available at http://www.ninds.nih.gov/health_and_medical/disorder_index.htm

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National Institute of Nursing Research (NINR); publications on selected illnesses at http://www.nih.gov/ninr/news-info/publications.html

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National Institute of Biomedical Imaging and Bioengineering; general information at http://grants.nih.gov/grants/becon/becon_info.htm

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Center for Information Technology (CIT); referrals to other agencies based on keyword searches available at http://kb.nih.gov/www_query_main.asp

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National Center for Complementary and Alternative Medicine (NCCAM); health information available at http://nccam.nih.gov/health/

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National Center for Research Resources (NCRR); various information directories available at http://www.ncrr.nih.gov/publications.asp

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Office of Rare Diseases; various fact sheets available at http://rarediseases.info.nih.gov/html/resources/rep_pubs.html

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Centers for Disease Control and Prevention; various fact sheets on infectious diseases available at http://www.cdc.gov/publications.htm

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NIH Databases In addition to the various Institutes of Health that publish professional guidelines, the NIH has designed a number of databases for professionals.13 Physician-oriented resources provide a wide variety of information related to the biomedical and health sciences, both past and present. The format of these resources varies. Searchable databases, bibliographic citations, full-text articles (when available), archival collections, and images are all available. The following are referenced by the National Library of Medicine:14 •

Bioethics: Access to published literature on the ethical, legal, and public policy issues surrounding healthcare and biomedical research. This information is provided in conjunction with the Kennedy Institute of Ethics located at Georgetown University, Washington, D.C.: http://www.nlm.nih.gov/databases/databases_bioethics.html

•

HIV/AIDS Resources: Describes various links and databases dedicated to HIV/AIDS research: http://www.nlm.nih.gov/pubs/factsheets/aidsinfs.html

•

NLM Online Exhibitions: Describes “Exhibitions in the History of Medicine”: http://www.nlm.nih.gov/exhibition/exhibition.html. Additional resources for historical scholarship in medicine: http://www.nlm.nih.gov/hmd/hmd.html

•

Biotechnology Information: Access to public databases. The National Center for Biotechnology Information conducts research in computational biology, develops software tools for analyzing genome data, and disseminates biomedical information for the better understanding of molecular processes affecting human health and disease: http://www.ncbi.nlm.nih.gov/

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Population Information: The National Library of Medicine provides access to worldwide coverage of population, family planning, and related health issues, including family planning technology and programs, fertility, and population law and policy: http://www.nlm.nih.gov/databases/databases_population.html

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Cancer Information: Access to cancer-oriented databases: http://www.nlm.nih.gov/databases/databases_cancer.html

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Profiles in Science: Offering the archival collections of prominent twentieth-century biomedical scientists to the public through modern digital technology: http://www.profiles.nlm.nih.gov/

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Chemical Information: Provides links to various chemical databases and references: http://sis.nlm.nih.gov/Chem/ChemMain.html

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Clinical Alerts: Reports the release of findings from the NIH-funded clinical trials where such release could significantly affect morbidity and mortality: http://www.nlm.nih.gov/databases/alerts/clinical_alerts.html

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Space Life Sciences: Provides links and information to space-based research (including NASA): http://www.nlm.nih.gov/databases/databases_space.html

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MEDLINE: Bibliographic database covering the fields of medicine, nursing, dentistry, veterinary medicine, the healthcare system, and the pre-clinical sciences: http://www.nlm.nih.gov/databases/databases_medline.html

13

Remember, for the general public, the National Library of Medicine recommends the databases referenced in MEDLINEplus (http://medlineplus.gov/ or http://www.nlm.nih.gov/medlineplus/databases.html). 14 See http://www.nlm.nih.gov/databases/databases.html.

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•

Toxicology and Environmental Health Information (TOXNET): Databases covering toxicology and environmental health: http://sis.nlm.nih.gov/Tox/ToxMain.html

•

Visible Human Interface: Anatomically detailed, three-dimensional representations of normal male and female human bodies: http://www.nlm.nih.gov/research/visible/visible_human.html

The NLM Gateway15 The NLM (National Library of Medicine) Gateway is a Web-based system that lets users search simultaneously in multiple retrieval systems at the U.S. National Library of Medicine (NLM). It allows users of NLM services to initiate searches from one Web interface, providing one-stop searching for many of NLM’s information resources or databases.16 To use the NLM Gateway, simply go to the search site at http://gateway.nlm.nih.gov/gw/Cmd. Type “E. coli” (or synonyms) into the search box and click “Search.” The results will be presented in a tabular form, indicating the number of references in each database category. Results Summary Category Journal Articles Books / Periodicals / Audio Visual Consumer Health Meeting Abstracts Other Collections Total

Items Found 175056 662 31 394 1 176144

HSTAT17 HSTAT is a free, Web-based resource that provides access to full-text documents used in healthcare decision-making.18 These documents include clinical practice guidelines, quickreference guides for clinicians, consumer health brochures, evidence reports and technology assessments from the Agency for Healthcare Research and Quality (AHRQ), as well as AHRQ’s Put Prevention Into Practice.19 Simply search by “E. coli” (or synonyms) at the following Web site: http://text.nlm.nih.gov.

15

Adapted from NLM: http://gateway.nlm.nih.gov/gw/Cmd?Overview.x.

16

The NLM Gateway is currently being developed by the Lister Hill National Center for Biomedical Communications (LHNCBC) at the National Library of Medicine (NLM) of the National Institutes of Health (NIH). 17 Adapted from HSTAT: http://www.nlm.nih.gov/pubs/factsheets/hstat.html. 18 19

The HSTAT URL is http://hstat.nlm.nih.gov/.

Other important documents in HSTAT include: the National Institutes of Health (NIH) Consensus Conference Reports and Technology Assessment Reports; the HIV/AIDS Treatment Information Service (ATIS) resource documents; the Substance Abuse and Mental Health Services Administration's Center for Substance Abuse Treatment (SAMHSA/CSAT) Treatment Improvement Protocols (TIP) and Center for Substance Abuse Prevention (SAMHSA/CSAP) Prevention Enhancement Protocols System (PEPS); the Public Health Service (PHS) Preventive Services Task Force's Guide to Clinical Preventive Services; the independent, nonfederal Task Force on Community Services’ Guide to Community Preventive Services; and the Health Technology Advisory Committee (HTAC) of the Minnesota Health Care Commission (MHCC) health technology evaluations.

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Coffee Break: Tutorials for Biologists20 Coffee Break is a general healthcare site that takes a scientific view of the news and covers recent breakthroughs in biology that may one day assist physicians in developing treatments. Here you will find a collection of short reports on recent biological discoveries. Each report incorporates interactive tutorials that demonstrate how bioinformatics tools are used as a part of the research process. Currently, all Coffee Breaks are written by NCBI staff.21 Each report is about 400 words and is usually based on a discovery reported in one or more articles from recently published, peer-reviewed literature.22 This site has new articles every few weeks, so it can be considered an online magazine of sorts. It is intended for general background information. You can access the Coffee Break Web site at the following hyperlink: http://www.ncbi.nlm.nih.gov/Coffeebreak/.

Other Commercial Databases In addition to resources maintained by official agencies, other databases exist that are commercial ventures addressing medical professionals. Here are some examples that may interest you: •

CliniWeb International: Index and table of contents to selected clinical information on the Internet; see http://www.ohsu.edu/cliniweb/.

•

Medical World Search: Searches full text from thousands of selected medical sites on the Internet; see http://www.mwsearch.com/.

The Genome Project and E. coli In the following section, we will discuss databases and references which relate to the Genome Project and E. coli. Online Mendelian Inheritance in Man (OMIM) The Online Mendelian Inheritance in Man (OMIM) database is a catalog of human genes and genetic disorders authored and edited by Dr. Victor A. McKusick and his colleagues at Johns Hopkins and elsewhere. OMIM was developed for the World Wide Web by the National Center for Biotechnology Information (NCBI).23 The database contains textual information, pictures, and reference information. It also contains copious links to NCBI’s Entrez database of MEDLINE articles and sequence information. 20 Adapted 21

from http://www.ncbi.nlm.nih.gov/Coffeebreak/Archive/FAQ.html.

The figure that accompanies each article is frequently supplied by an expert external to NCBI, in which case the source of the figure is cited. The result is an interactive tutorial that tells a biological story. 22 After a brief introduction that sets the work described into a broader context, the report focuses on how a molecular understanding can provide explanations of observed biology and lead to therapies for diseases. Each vignette is accompanied by a figure and hypertext links that lead to a series of pages that interactively show how NCBI tools and resources are used in the research process. 23 Adapted from http://www.ncbi.nlm.nih.gov/. Established in 1988 as a national resource for molecular biology information, NCBI creates public databases, conducts research in computational biology, develops software tools for analyzing genome data, and disseminates biomedical information--all for the better understanding of molecular processes affecting human health and disease.

266 E. coli

To search the database, go to http://www.ncbi.nlm.nih.gov/Omim/searchomim.html. Type “E. coli” (or synonyms) into the search box, and click “Submit Search.” If too many results appear, you can narrow the search by adding the word “clinical.” Each report will have additional links to related research and databases. In particular, the option “Database Links” will search across technical databases that offer an abundance of information. The following is an example of the results you can obtain from the OMIM for E. coli: •

Alkb, E. coli, Homolog of Web site: http://www.ncbi.nlm.nih.gov/htbin-post/Omim/dispmim?605345

•

Dnaj, E. coli, Homolog Of, Subfamily A, Member 1 Web site: http://www.ncbi.nlm.nih.gov/htbin-post/Omim/dispmim?602837

•

Muts, E. coli, Homolog Of, 4 Web site: http://www.ncbi.nlm.nih.gov/htbin-post/Omim/dispmim?602105

•

Muty, E. coli, Homolog of Web site: http://www.ncbi.nlm.nih.gov/htbin-post/Omim/dispmim?604933 Genes and Disease (NCBI - Map)

The Genes and Disease database is produced by the National Center for Biotechnology Information of the National Library of Medicine at the National Institutes of Health. This Web site categorizes each disorder by system of the body. Go to http://www.ncbi.nlm.nih.gov/disease/, and browse the system pages to have a full view of important conditions linked to human genes. Since this site is regularly updated, you may wish to revisit it from time to time. The following systems and associated disorders are addressed: •

Cancer: Uncontrolled cell division. Examples: Breast and ovarian cancer, Burkitt lymphoma, chronic myeloid leukemia, colon cancer, lung cancer, malignant melanoma, multiple endocrine neoplasia, neurofibromatosis, p53 tumor suppressor, pancreatic cancer, prostate cancer, Ras oncogene, RB: retinoblastoma, von Hippel-Lindau syndrome. Web site: http://www.ncbi.nlm.nih.gov/disease/Cancer.html

•

Immune System: Fights invaders. Examples: Asthma, autoimmune polyglandular syndrome, Crohn’s disease, DiGeorge syndrome, familial Mediterranean fever, immunodeficiency with Hyper-IgM, severe combined immunodeficiency. Web site: http://www.ncbi.nlm.nih.gov/disease/Immune.html

•

Metabolism: Food and energy. Examples: Adreno-leukodystrophy, atherosclerosis, Best disease, Gaucher disease, glucose galactose malabsorption, gyrate atrophy, juvenile-onset diabetes, obesity, paroxysmal nocturnal hemoglobinuria, phenylketonuria, Refsum disease, Tangier disease, Tay-Sachs disease. Web site: http://www.ncbi.nlm.nih.gov/disease/Metabolism.html

•

Muscle and Bone: Movement and growth. Examples: Duchenne muscular dystrophy, Ellis-van Creveld syndrome, Marfan syndrome, myotonic dystrophy, spinal muscular atrophy. Web site: http://www.ncbi.nlm.nih.gov/disease/Muscle.html

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•

Nervous System: Mind and body. Examples: Alzheimer disease, amyotrophic lateral sclerosis, Angelman syndrome, Charcot-Marie-Tooth disease, epilepsy, essential tremor, fragile X syndrome, Friedreich’s ataxia, Huntington disease, Niemann-Pick disease, Parkinson disease, Prader-Willi syndrome, Rett syndrome, spinocerebellar atrophy, Williams syndrome. Web site: http://www.ncbi.nlm.nih.gov/disease/Brain.html

•

Signals: Cellular messages. Examples: Ataxia telangiectasia, Cockayne syndrome, glaucoma, male-patterned baldness, SRY: sex determination, tuberous sclerosis, Waardenburg syndrome, Werner syndrome. Web site: http://www.ncbi.nlm.nih.gov/disease/Signals.html

•

Transporters: Pumps and channels. Examples: Cystic fibrosis, deafness, diastrophic dysplasia, Hemophilia A, long-QT syndrome, Menkes syndrome, Pendred syndrome, polycystic kidney disease, sickle cell anemia, Wilson’s disease, Zellweger syndrome. Web site: http://www.ncbi.nlm.nih.gov/disease/Transporters.html Entrez

Entrez is a search and retrieval system that integrates several linked databases at the National Center for Biotechnology Information (NCBI). These databases include nucleotide sequences, protein sequences, macromolecular structures, whole genomes, and MEDLINE through PubMed. Entrez provides access to the following databases: •

3D Domains: Domains from Entrez Structure, Web site: http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=geo

•

Books: Online books, Web site: http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=books

•

Genome: Complete genome assemblies, Web site: http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=Genome

•

NCBI’s Protein Sequence Information Survey Results: Web site: http://www.ncbi.nlm.nih.gov/About/proteinsurvey/

•

Nucleotide Sequence Database (Genbank): Web site: http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=Nucleotide

•

OMIM: Online Mendelian Inheritance in Man, Web site: http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=OMIM

•

PopSet: Population study data sets, Web site: http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=Popset

•

ProbeSet: Gene Expression Omnibus (GEO), Web site: http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=geo

•

Protein Sequence Database: Web site: http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=Protein

•

PubMed: Biomedical literature (PubMed), Web site: http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed

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•

Structure: Three-dimensional macromolecular structures, Web site: http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=Structure

•

Taxonomy: Organisms in GenBank, Web site: http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=Taxonomy

To access the Entrez system at the National Center for Biotechnology Information, go to http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?CMD=search&DB=genome, and then select the database that you would like to search. The databases available are listed in the drop box next to “Search.” Enter “E. coli” (or synonyms) into the search box and click “Go.” Jablonski’s Multiple Congenital Anomaly/Mental Retardation (MCA/MR) Syndromes Database24 This online resource has been developed to facilitate the identification and differentiation of syndromic entities. Special attention is given to the type of information that is usually limited or completely omitted in existing reference sources due to space limitations of the printed form. At http://www.nlm.nih.gov/mesh/jablonski/syndrome_toc/toc_a.html, you can search across syndromes using an alphabetical index. Search by keywords at http://www.nlm.nih.gov/mesh/jablonski/syndrome_db.html. The Genome Database25 Established at Johns Hopkins University in Baltimore, Maryland in 1990, the Genome Database (GDB) is the official central repository for genomic mapping data resulting from the Human Genome Initiative. In the spring of 1999, the Bioinformatics Supercomputing Centre (BiSC) at the Hospital for Sick Children in Toronto, Ontario assumed the management of GDB. The Human Genome Initiative is a worldwide research effort focusing on structural analysis of human DNA to determine the location and sequence of the estimated 100,000 human genes. In support of this project, GDB stores and curates data generated by researchers worldwide who are engaged in the mapping effort of the Human Genome Project (HGP). GDB’s mission is to provide scientists with an encyclopedia of the human genome which is continually revised and updated to reflect the current state of scientific knowledge. Although GDB has historically focused on gene mapping, its focus will broaden as the Genome Project moves from mapping to sequence, and finally, to functional analysis. To access the GDB, simply go to the following hyperlink: http://www.gdb.org/. Search “All Biological Data” by “Keyword.” Type “E. coli” (or synonyms) into the search box, and review the results. If more than one word is used in the search box, then separate each one with the word “and” or “or” (using “or” might be useful when using synonyms). 24

Adapted from the National Library of Medicine: http://www.nlm.nih.gov/mesh/jablonski/about_syndrome.html. 25 Adapted from the Genome Database: http://gdbwww.gdb.org/gdb/aboutGDB.html - mission.

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APPENDIX B. PATIENT RESOURCES Overview Official agencies, as well as federally funded institutions supported by national grants, frequently publish a variety of guidelines written with the patient in mind. These are typically called “Fact Sheets” or “Guidelines.” They can take the form of a brochure, information kit, pamphlet, or flyer. Often they are only a few pages in length. Since new guidelines on E. coli can appear at any moment and be published by a number of sources, the best approach to finding guidelines is to systematically scan the Internet-based services that post them.

Patient Guideline Sources The remainder of this chapter directs you to sources which either publish or can help you find additional guidelines on topics related to E. coli. Due to space limitations, these sources are listed in a concise manner. Do not hesitate to consult the following sources by either using the Internet hyperlink provided, or, in cases where the contact information is provided, contacting the publisher or author directly. The National Institutes of Health The NIH gateway to patients is located at http://health.nih.gov/. From this site, you can search across various sources and institutes, a number of which are summarized below. Topic Pages: MEDLINEplus The National Library of Medicine has created a vast and patient-oriented healthcare information portal called MEDLINEplus. Within this Internet-based system are “health topic pages” which list links to available materials relevant to E. coli. To access this system, log on to http://www.nlm.nih.gov/medlineplus/healthtopics.html. From there you can either search using the alphabetical index or browse by broad topic areas. Recently, MEDLINEplus listed the following when searched for “E. coli”:

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•

Other guides Bacterial Infections http://www.nlm.nih.gov/medlineplus/bacterialinfections.html Drinking Water http://www.nlm.nih.gov/medlineplus/drinkingwater.html E. coli Infections http://www.nlm.nih.gov/medlineplus/ecoliinfections.html Food Contamination/Poisoning http://www.nlm.nih.gov/medlineplus/foodcontaminationpoisoning.html Food Safety http://www.nlm.nih.gov/medlineplus/foodsafety.html Salmonella Infections http://www.nlm.nih.gov/medlineplus/salmonellainfections.html

Within the health topic page dedicated to E. coli, the following was listed: •

General/Overviews E. coli Infection Source: American Academy of Family Physicians http://familydoctor.org/handouts/242.html Escherichia Coli O157:H7 Source: National Center for Infectious Diseases http://www.cdc.gov/ncidod/dbmd/diseaseinfo/escherichiacoli_g.htm

•

Specific Conditions/Aspects E. coli in Drinking Water Source: Environmental Protection Agency http://www.epa.gov/safewater/ecoli.html Enteroinvasive Escherichia coli Source: Center for Food Safety and Applied Nutrition http://vm.cfsan.fda.gov/%7Emow/chap16.html Enteropathogenic Escherichia Coli Source: Center for Food Safety and Applied Nutrition http://vm.cfsan.fda.gov/%7Emow/chap14.html Enterotoxigenic Escherichia Coli (ETEC) Source: National Center for Infectious Diseases http://www.cdc.gov/ncidod/dbmd/diseaseinfo/etec_g.htm Escherichia Coli Infection and Farm Animals Source: National Center for Infectious Diseases http://www.cdc.gov/healthypets/diseases/ecoli.htm Focus on Ground Beef Source: Dept. of Agriculture, Food Safety and Inspection Service http://www.fsis.usda.gov/oa/pubs/focusgb.htm

Patient Resources

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Children E. coli Source: Nemours Foundation http://kidshealth.org/kid/stay_healthy/food/ecoli.html

•

Law and Policy What to Do If You Have a Problem with Food Products Source: Dept. of Agriculture, Food Safety and Inspection Service http://www.fsis.usda.gov/oa/pubs/illness.htm

•

Organizations Food Safety and Inspection Service Source: Dept. of Agriculture http://www.fsis.usda.gov/ National Center for Infectious Diseases http://www.cdc.gov/ncidod/index.htm National Institute of Allergy and Infectious Diseases http://www.niaid.nih.gov/ Partnership for Food Safety Education http://www.fightbac.org

•

Prevention/Screening E.Coli: Preventing a Common Type of Food Poisoning Source: Mayo Foundation for Medical Education and Research http://www.mayoclinic.com/invoke.cfm?id=DG00005 Lactoferrin Considered Safe to Fight E. coli Source: Food and Drug Administration http://www.fda.gov/bbs/topics/NEWS/2003/NEW00935.html Use a Food Thermometer Source: Dept. of Agriculture, Food Safety and Inspection Service http://www.fsis.usda.gov/OA/thermy/bro_text.htm

•

Research ARS Scientists Devise New Test for E. coli O157 in Water Source: Agricultural Research Service http://www.ars.usda.gov/is/pr/2002/020306.htm Gene Sequence of Deadly E. coli Reveals Surprisingly Dynamic Genome Source: National Institute of Allergy and Infectious Diseases http://www.niaid.nih.gov/newsroom/releases/0157h7.htm Reducing Salmonella and E. coli 0157:H7 at the Farm Source: Agricultural Research Service http://www.ars.usda.gov/is/pr/2001/010305.htm

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•

Statistics Microbiological Results of Raw Ground Beef Products Analyzed for Escherichia Coli O157:H7 Calendar Year 2002 Source: Dept. of Agriculture, Food Safety and Inspection Service http://www.fsis.usda.gov/OPHS/ecoltest/ecpositives.htm

You may also choose to use the search utility provided by MEDLINEplus at the following Web address: http://www.nlm.nih.gov/medlineplus/. Simply type a keyword into the search box and click “Search.” This utility is similar to the NIH search utility, with the exception that it only includes materials that are linked within the MEDLINEplus system (mostly patient-oriented information). It also has the disadvantage of generating unstructured results. We recommend, therefore, that you use this method only if you have a very targeted search. The Combined Health Information Database (CHID) CHID Online is a reference tool that maintains a database directory of thousands of journal articles and patient education guidelines on E. coli. CHID offers summaries that describe the guidelines available, including contact information and pricing. CHID’s general Web site is http://chid.nih.gov/. To search this database, go to http://chid.nih.gov/detail/detail.html. In particular, you can use the advanced search options to look up pamphlets, reports, brochures, and information kits. The following was recently posted in this archive: •

Is Your Food Safe? Source: Santa Cruz, CA: ETR Associates. 1998. 6 p. Contact: Available from ETR Associates. 4 Carbonero Way, Scotts Valley, CA 950664200. (800) 321-4407. Fax (800) 435-8433. Website: www.etr.org. PRICE: Single copy free; bulk copies available. Order number: R027. Summary: This brochure describes foodborne illnesses and their prevention. If food is poorly handled or not cooked or stored properly, bacteria can multiply and cause illness. Not everyone who eats contaminated food will become sick. The symptoms depend on which organism was eaten, how much was eaten, and what the age and general health of the person are. Symptoms of food poisoning are similar to those of stomach flu and include nausea, vomiting, diarrhea, stomach pain or cramps, and fever, fatigue, and feelings of weakness. The brochure lists nine organisms and how they are usually transmitted; organisms and diseases discussed are botulism, Campylobacter, Crytosporidiosis, cyclospora, E. coli (0157:H7), hepatitis A, listeriosis, Salmonella, and Vibrio vulnificus. The brochure notes that mild illness usually gets better on its own and provides basic strategies for handling symptoms of mild food poisoning. The brochure also lists symptoms that would indicate the need to contact a health care provider and notes people more at risk for problems from food poisoning. The centerpiece of the brochure offers U.S. Department of Agriculture strategies for keeping food safe: the six areas covered are buying, storing, preparing, cooking, and serving food, and eating out. A chart summarizes the time that fresh meat, fish, poultry, cheese, eggs, and milk will last in the refrigerator or in the freezer. One sidebar lists safe kitchen tips (primarily relating to hygiene).

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Healthfinder™ Healthfinder™ is sponsored by the U.S. Department of Health and Human Services and offers links to hundreds of other sites that contain healthcare information. This Web site is located at http://www.healthfinder.gov. Again, keyword searches can be used to find guidelines. The following was recently found in this database: •

Foodborne Diseases Summary: This online fact sheet provides a description of the more common and serious foodborne illnesses -- Escherichia coli (E. coli), Salmonellosis, Campylobacteriosis, and Shigellosis. Source: National Institute of Allergy and Infectious Diseases, National Institutes of Health http://www.healthfinder.gov/scripts/recordpass.asp?RecordType=0&RecordID=2381

•

Hemolytic Uremic Syndrome Summary: An overview of hemolytic uremic syndrome, its relationship to E. coli, and its symptoms and treatment. Source: National Institute of Diabetes and Digestive and Kidney Diseases, National Institutes of Health http://www.healthfinder.gov/scripts/recordpass.asp?RecordType=0&RecordID=6511 The NIH Search Utility

The NIH search utility allows you to search for documents on over 100 selected Web sites that comprise the NIH-WEB-SPACE. Each of these servers is “crawled” and indexed on an ongoing basis. Your search will produce a list of various documents, all of which will relate in some way to E. coli. The drawbacks of this approach are that the information is not organized by theme and that the references are often a mix of information for professionals and patients. Nevertheless, a large number of the listed Web sites provide useful background information. We can only recommend this route, therefore, for relatively rare or specific disorders, or when using highly targeted searches. To use the NIH search utility, visit the following Web page: http://search.nih.gov/index.html. Additional Web Sources A number of Web sites are available to the public that often link to government sites. These can also point you in the direction of essential information. The following is a representative sample: •


•

Family Village: http://www.familyvillage.wisc.edu/specific.htm

•

Google: http://directory.google.com/Top/Health/Conditions_and_Diseases/

•

Med Help International: http://www.medhelp.org/HealthTopics/A.html

•

Open Directory Project: http://dmoz.org/Health/Conditions_and_Diseases/

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•

Yahoo.com: http://dir.yahoo.com/Health/Diseases_and_Conditions/

•

WebMDHealth: http://my.webmd.com/health_topics

Finding Associations There are several Internet directories that provide lists of medical associations with information on or resources relating to E. coli. By consulting all of associations listed in this chapter, you will have nearly exhausted all sources for patient associations concerned with E. coli. The National Health Information Center (NHIC) The National Health Information Center (NHIC) offers a free referral service to help people find organizations that provide information about E. coli. For more information, see the NHIC’s Web site at http://www.health.gov/NHIC/ or contact an information specialist by calling 1-800-336-4797. Directory of Health Organizations The Directory of Health Organizations, provided by the National Library of Medicine Specialized Information Services, is a comprehensive source of information on associations. The Directory of Health Organizations database can be accessed via the Internet at http://www.sis.nlm.nih.gov/Dir/DirMain.html. It is composed of two parts: DIRLINE and Health Hotlines. The DIRLINE database comprises some 10,000 records of organizations, research centers, and government institutes and associations that primarily focus on health and biomedicine. To access DIRLINE directly, go to the following Web site: http://dirline.nlm.nih.gov/. Simply type in “E. coli” (or a synonym), and you will receive information on all relevant organizations listed in the database. Health Hotlines directs you to toll-free numbers to over 300 organizations. You can access this database directly at http://www.sis.nlm.nih.gov/hotlines/. On this page, you are given the option to search by keyword or by browsing the subject list. When you have received your search results, click on the name of the organization for its description and contact information. The Combined Health Information Database Another comprehensive source of information on healthcare associations is the Combined Health Information Database. Using the “Detailed Search” option, you will need to limit your search to “Organizations” and “E. coli”. Type the following hyperlink into your Web browser: http://chid.nih.gov/detail/detail.html. To find associations, use the drop boxes at the bottom of the search page where “You may refine your search by.” For publication date, select “All Years.” Then, select your preferred language and the format option “Organization Resource Sheet.” Type “E. coli” (or synonyms) into the “For these words:”

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box. You should check back periodically with this database since it is updated every three months. The National Organization for Rare Disorders, Inc. The National Organization for Rare Disorders, Inc. has prepared a Web site that provides, at no charge, lists of associations organized by health topic. You can access this database at the following Web site: http://www.rarediseases.org/search/orgsearch.html. Type “E. coli” (or a synonym) into the search box, and click “Submit Query.”

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APPENDIX C. FINDING MEDICAL LIBRARIES Overview In this Appendix, we show you how to quickly find a medical library in your area.

Preparation Your local public library and medical libraries have interlibrary loan programs with the National Library of Medicine (NLM), one of the largest medical collections in the world. According to the NLM, most of the literature in the general and historical collections of the National Library of Medicine is available on interlibrary loan to any library. If you would like to access NLM medical literature, then visit a library in your area that can request the publications for you.26

Finding a Local Medical Library The quickest method to locate medical libraries is to use the Internet-based directory published by the National Network of Libraries of Medicine (NN/LM). This network includes 4626 members and affiliates that provide many services to librarians, health professionals, and the public. To find a library in your area, simply visit http://nnlm.gov/members/adv.html or call 1-800-338-7657.

Medical Libraries in the U.S. and Canada In addition to the NN/LM, the National Library of Medicine (NLM) lists a number of libraries with reference facilities that are open to the public. The following is the NLM’s list and includes hyperlinks to each library’s Web site. These Web pages can provide information on hours of operation and other restrictions. The list below is a small sample of

26

Adapted from the NLM: http://www.nlm.nih.gov/psd/cas/interlibrary.html.

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libraries recommended by the National Library of Medicine (sorted alphabetically by name of the U.S. state or Canadian province where the library is located)27: •

Alabama: Health InfoNet of Jefferson County (Jefferson County Library Cooperative, Lister Hill Library of the Health Sciences), http://www.uab.edu/infonet/

•

Alabama: Richard M. Scrushy Library (American Sports Medicine Institute)

•

Arizona: Samaritan Regional Medical Center: The Learning Center (Samaritan Health System, Phoenix, Arizona), http://www.samaritan.edu/library/bannerlibs.htm

•

California: Kris Kelly Health Information Center (St. Joseph Health System, Humboldt), http://www.humboldt1.com/~kkhic/index.html

•

California: Community Health Library of Los Gatos, http://www.healthlib.org/orgresources.html

•

California: Consumer Health Program and Services (CHIPS) (County of Los Angeles Public Library, Los Angeles County Harbor-UCLA Medical Center Library) - Carson, CA, http://www.colapublib.org/services/chips.html

•

California: Gateway Health Library (Sutter Gould Medical Foundation)

•

California: Health Library (Stanford University Medical Center), http://wwwmed.stanford.edu/healthlibrary/

•

California: Patient Education Resource Center - Health Information and Resources (University of California, San Francisco), http://sfghdean.ucsf.edu/barnett/PERC/default.asp

•

California: Redwood Health Library (Petaluma Health Care District), http://www.phcd.org/rdwdlib.html

•

California: Los Gatos PlaneTree Health Library, http://planetreesanjose.org/

•

California: Sutter Resource Library (Sutter Hospitals Foundation, Sacramento), http://suttermedicalcenter.org/library/

•

California: Health Sciences Libraries (University of California, Davis), http://www.lib.ucdavis.edu/healthsci/

•

California: ValleyCare Health Library & Ryan Comer Cancer Resource Center (ValleyCare Health System, Pleasanton), http://gaelnet.stmarysca.edu/other.libs/gbal/east/vchl.html

•

California: Washington Community Health Resource Library (Fremont), http://www.healthlibrary.org/

•

Colorado: William V. Gervasini Memorial Library (Exempla Healthcare), http://www.saintjosephdenver.org/yourhealth/libraries/

•

Connecticut: Hartford Hospital Health Science Libraries (Hartford Hospital), http://www.harthosp.org/library/

•

Connecticut: Healthnet: Connecticut Consumer Health Information Center (University of Connecticut Health Center, Lyman Maynard Stowe Library), http://library.uchc.edu/departm/hnet/

27

Abstracted from http://www.nlm.nih.gov/medlineplus/libraries.html.

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•

Connecticut: Waterbury Hospital Health Center Library (Waterbury Hospital, Waterbury), http://www.waterburyhospital.com/library/consumer.shtml

•

Delaware: Consumer Health Library (Christiana Care Health System, Eugene du Pont Preventive Medicine & Rehabilitation Institute, Wilmington), http://www.christianacare.org/health_guide/health_guide_pmri_health_info.cfm

•

Delaware: Lewis B. Flinn Library (Delaware Academy of Medicine, Wilmington), http://www.delamed.org/chls.html

•

Georgia: Family Resource Library (Medical College of Georgia, Augusta), http://cmc.mcg.edu/kids_families/fam_resources/fam_res_lib/frl.htm

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Georgia: Health Resource Center (Medical Center of Central Georgia, Macon), http://www.mccg.org/hrc/hrchome.asp

•

Hawaii: Hawaii Medical Library: Consumer Health Information Service (Hawaii Medical Library, Honolulu), http://hml.org/CHIS/

•

Idaho: DeArmond Consumer Health Library (Kootenai Medical Center, Coeur d’Alene), http://www.nicon.org/DeArmond/index.htm

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Illinois: Health Learning Center of Northwestern Memorial Hospital (Chicago), http://www.nmh.org/health_info/hlc.html

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Illinois: Medical Library (OSF Saint Francis Medical Center, Peoria), http://www.osfsaintfrancis.org/general/library/

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Kentucky: Medical Library - Services for Patients, Families, Students & the Public (Central Baptist Hospital, Lexington), http://www.centralbap.com/education/community/library.cfm

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Kentucky: University of Kentucky - Health Information Library (Chandler Medical Center, Lexington), http://www.mc.uky.edu/PatientEd/

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Louisiana: Alton Ochsner Medical Foundation Library (Alton Ochsner Medical Foundation, New Orleans), http://www.ochsner.org/library/

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Louisiana: Louisiana State University Health Sciences Center Medical LibraryShreveport, http://lib-sh.lsuhsc.edu/

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Maine: Franklin Memorial Hospital Medical Library (Franklin Memorial Hospital, Farmington), http://www.fchn.org/fmh/lib.htm

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Maine: Gerrish-True Health Sciences Library (Central Maine Medical Center, Lewiston), http://www.cmmc.org/library/library.html

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Maine: Hadley Parrot Health Science Library (Eastern Maine Healthcare, Bangor), http://www.emh.org/hll/hpl/guide.htm

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Maine: Maine Medical Center Library (Maine Medical Center, Portland), http://www.mmc.org/library/

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Maine: Parkview Hospital (Brunswick), http://www.parkviewhospital.org/

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Maine: Southern Maine Medical Center Health Sciences Library (Southern Maine Medical Center, Biddeford), http://www.smmc.org/services/service.php3?choice=10

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Maine: Stephens Memorial Hospital’s Health Information Library (Western Maine Health, Norway), http://www.wmhcc.org/Library/

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Manitoba, Canada: Consumer & Patient Health Information Service (University of Manitoba Libraries), http://www.umanitoba.ca/libraries/units/health/reference/chis.html

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Manitoba, Canada: J.W. Crane Memorial Library (Deer Lodge Centre, Winnipeg), http://www.deerlodge.mb.ca/crane_library/about.asp

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Maryland: Health Information Center at the Wheaton Regional Library (Montgomery County, Dept. of Public Libraries, Wheaton Regional Library), http://www.mont.lib.md.us/healthinfo/hic.asp

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Massachusetts: Baystate Medical Center Library (Baystate Health System), http://www.baystatehealth.com/1024/

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Massachusetts: Boston University Medical Center Alumni Medical Library (Boston University Medical Center), http://med-libwww.bu.edu/library/lib.html

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Massachusetts: Lowell General Hospital Health Sciences Library (Lowell General Hospital, Lowell), http://www.lowellgeneral.org/library/HomePageLinks/WWW.htm

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Massachusetts: Paul E. Woodard Health Sciences Library (New England Baptist Hospital, Boston), http://www.nebh.org/health_lib.asp

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Massachusetts: St. Luke’s Hospital Health Sciences Library (St. Luke’s Hospital, Southcoast Health System, New Bedford), http://www.southcoast.org/library/

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Massachusetts: Treadwell Library Consumer Health Reference Center (Massachusetts General Hospital), http://www.mgh.harvard.edu/library/chrcindex.html

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Massachusetts: UMass HealthNet (University of Massachusetts Medical School, Worchester), http://healthnet.umassmed.edu/

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Michigan: Botsford General Hospital Library - Consumer Health (Botsford General Hospital, Library & Internet Services), http://www.botsfordlibrary.org/consumer.htm

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Michigan: Helen DeRoy Medical Library (Providence Hospital and Medical Centers), http://www.providence-hospital.org/library/

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Michigan: Marquette General Hospital - Consumer Health Library (Marquette General Hospital, Health Information Center), http://www.mgh.org/center.html

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Michigan: Patient Education Resouce Center - University of Michigan Cancer Center (University of Michigan Comprehensive Cancer Center, Ann Arbor), http://www.cancer.med.umich.edu/learn/leares.htm

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Michigan: Sladen Library & Center for Health Information Resources - Consumer Health Information (Detroit), http://www.henryford.com/body.cfm?id=39330

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Montana: Center for Health Information (St. Patrick Hospital and Health Sciences Center, Missoula)

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National: Consumer Health Library Directory (Medical Library Association, Consumer and Patient Health Information Section), http://caphis.mlanet.org/directory/index.html

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National: National Network of Libraries of Medicine (National Library of Medicine) provides library services for health professionals in the United States who do not have access to a medical library, http://nnlm.gov/

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National: NN/LM List of Libraries Serving the Public (National Network of Libraries of Medicine), http://nnlm.gov/members/

Finding Medical Libraries

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Nevada: Health Science Library, West Charleston Library (Las Vegas-Clark County Library District, Las Vegas), http://www.lvccld.org/special_collections/medical/index.htm

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New Hampshire: Dartmouth Biomedical Libraries (Dartmouth College Library, Hanover), http://www.dartmouth.edu/~biomed/resources.htmld/conshealth.htmld/

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New Jersey: Consumer Health Library (Rahway Hospital, Rahway), http://www.rahwayhospital.com/library.htm

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New Jersey: Dr. Walter Phillips Health Sciences Library (Englewood Hospital and Medical Center, Englewood), http://www.englewoodhospital.com/links/index.htm

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New Jersey: Meland Foundation (Englewood Hospital and Medical Center, Englewood), http://www.geocities.com/ResearchTriangle/9360/

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New York: Choices in Health Information (New York Public Library) - NLM Consumer Pilot Project participant, http://www.nypl.org/branch/health/links.html

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New York: Health Information Center (Upstate Medical University, State University of New York, Syracuse), http://www.upstate.edu/library/hic/

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New York: Health Sciences Library (Long Island Jewish Medical Center, New Hyde Park), http://www.lij.edu/library/library.html

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New York: ViaHealth Medical Library (Rochester General Hospital), http://www.nyam.org/library/

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Ohio: Consumer Health Library (Akron General Medical Center, Medical & Consumer Health Library), http://www.akrongeneral.org/hwlibrary.htm

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Oklahoma: The Health Information Center at Saint Francis Hospital (Saint Francis Health System, Tulsa), http://www.sfh-tulsa.com/services/healthinfo.asp

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Oregon: Planetree Health Resource Center (Mid-Columbia Medical Center, The Dalles), http://www.mcmc.net/phrc/

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Pennsylvania: Community Health Information Library (Milton S. Hershey Medical Center, Hershey), http://www.hmc.psu.edu/commhealth/

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Pennsylvania: Community Health Resource Library (Geisinger Medical Center, Danville), http://www.geisinger.edu/education/commlib.shtml

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Pennsylvania: HealthInfo Library (Moses Taylor Hospital, Scranton), http://www.mth.org/healthwellness.html

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Pennsylvania: Hopwood Library (University of Pittsburgh, Health Sciences Library System, Pittsburgh), http://www.hsls.pitt.edu/guides/chi/hopwood/index_html

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Pennsylvania: Koop Community Health Information Center (College of Physicians of Philadelphia), http://www.collphyphil.org/kooppg1.shtml

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Pennsylvania: Learning Resources Center - Medical Library (Susquehanna Health System, Williamsport), http://www.shscares.org/services/lrc/index.asp

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Pennsylvania: Medical Library (UPMC Health System, Pittsburgh), http://www.upmc.edu/passavant/library.htm

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Quebec, Canada: Medical Library (Montreal General Hospital), http://www.mghlib.mcgill.ca/

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South Dakota: Rapid City Regional Hospital Medical Library (Rapid City Regional Hospital), http://www.rcrh.org/Services/Library/Default.asp

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Texas: Houston HealthWays (Houston Academy of Medicine-Texas Medical Center Library), http://hhw.library.tmc.edu/

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Washington: Community Health Library (Kittitas Valley Community Hospital), http://www.kvch.com/

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Washington: Southwest Washington Medical Center Library (Southwest Washington Medical Center, Vancouver), http://www.swmedicalcenter.com/body.cfm?id=72

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ONLINE GLOSSARIES The Internet provides access to a number of free-to-use medical dictionaries. The National Library of Medicine has compiled the following list of online dictionaries: •

ADAM Medical Encyclopedia (A.D.A.M., Inc.), comprehensive medical reference: http://www.nlm.nih.gov/medlineplus/encyclopedia.html

•

MedicineNet.com Medical Dictionary (MedicineNet, Inc.): http://www.medterms.com/Script/Main/hp.asp

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Merriam-Webster Medical Dictionary (Inteli-Health, Inc.): http://www.intelihealth.com/IH/

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Multilingual Glossary of Technical and Popular Medical Terms in Eight European Languages (European Commission) - Danish, Dutch, English, French, German, Italian, Portuguese, and Spanish: http://allserv.rug.ac.be/~rvdstich/eugloss/welcome.html

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On-line Medical Dictionary (CancerWEB): http://cancerweb.ncl.ac.uk/omd/

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Rare Diseases Terms (Office of Rare Diseases): http://ord.aspensys.com/asp/diseases/diseases.asp

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Technology Glossary (National Library of Medicine) - Health Care Technology: http://www.nlm.nih.gov/nichsr/ta101/ta10108.htm

Beyond these, MEDLINEplus contains a very patient-friendly encyclopedia covering every aspect of medicine (licensed from A.D.A.M., Inc.). The ADAM Medical Encyclopedia can be accessed at http://www.nlm.nih.gov/medlineplus/encyclopedia.html. ADAM is also available on commercial Web sites such as drkoop.com (http://www.drkoop.com/) and Web MD (http://my.webmd.com/adam/asset/adam_disease_articles/a_to_z/a).

Online Dictionary Directories The following are additional online directories compiled by the National Library of Medicine, including a number of specialized medical dictionaries: •

Medical Dictionaries: Medical & Biological (World Health Organization): http://www.who.int/hlt/virtuallibrary/English/diction.htm#Medical

•

MEL-Michigan Electronic Library List of Online Health and Medical Dictionaries (Michigan Electronic Library): http://mel.lib.mi.us/health/health-dictionaries.html

•

Patient Education: Glossaries (DMOZ Open Directory Project): http://dmoz.org/Health/Education/Patient_Education/Glossaries/

•

Web of Online Dictionaries (Bucknell University): http://www.yourdictionary.com/diction5.html#medicine

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E. COLI DICTIONARY The definitions below are derived from official public sources, including the National Institutes of Health [NIH] and the European Union [EU]. Abdomen: That portion of the body that lies between the thorax and the pelvis. [NIH] Abdominal: Having to do with the abdomen, which is the part of the body between the chest and the hips that contains the pancreas, stomach, intestines, liver, gallbladder, and other organs. [NIH] Abdominal Pain: Sensation of discomfort, distress, or agony in the abdominal region. [NIH] Aberrant: Wandering or deviating from the usual or normal course. [EU] Acceptor: A substance which, while normally not oxidized by oxygen or reduced by hydrogen, can be oxidized or reduced in presence of a substance which is itself undergoing oxidation or reduction. [NIH] Acetylcholine: A neurotransmitter. Acetylcholine in vertebrates is the major transmitter at neuromuscular junctions, autonomic ganglia, parasympathetic effector junctions, a subset of sympathetic effector junctions, and at many sites in the central nervous system. It is generally not used as an administered drug because it is broken down very rapidly by cholinesterases, but it is useful in some ophthalmological applications. [NIH] Acetylgalactosamine: The N-acetyl derivative of galactosamine. [NIH] Acquired Immunodeficiency Syndrome: An acquired defect of cellular immunity associated with infection by the human immunodeficiency virus (HIV), a CD4-positive Tlymphocyte count under 200 cells/microliter or less than 14% of total lymphocytes, and increased susceptibility to opportunistic infections and malignant neoplasms. Clinical manifestations also include emaciation (wasting) and dementia. These elements reflect criteria for AIDS as defined by the CDC in 1993. [NIH] Acremonium: A mitosporic fungal genus with many reported ascomycetous teleomorphs. Cephalosporin antibiotics are derived from this genus. [NIH] Acrylonitrile: A highly poisonous compound used widely in the manufacture of plastics, adhesives and synthetic rubber. [NIH] Actin: Essential component of the cell skeleton. [NIH] Acute lymphoblastic leukemia: ALL. A quickly progressing disease in which too many immature white blood cells called lymphoblasts are found in the blood and bone marrow. Also called acute lymphocytic leukemia. [NIH] Acute lymphocytic leukemia: ALL. A quickly progressing disease in which too many immature white blood cells called lymphoblasts are found in the blood and bone marrow. Also called acute lymphoblastic leukemia. [NIH] Acute renal: A condition in which the kidneys suddenly stop working. In most cases, kidneys can recover from almost complete loss of function. [NIH] Acyl: Chemical signal used by bacteria to communicate. [NIH] Acyl Carrier Protein: Consists of a polypeptide chain and 4'-phosphopantetheine linked to a serine residue by a phosphodiester bond. Acyl groups are bound as thiol esters to the pantothenyl group. Acyl carrier protein is involved in every step of fatty acid synthesis by the cytoplasmic system. [NIH]

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Adaptability: Ability to develop some form of tolerance to conditions extremely different from those under which a living organism evolved. [NIH] Adaptation: 1. The adjustment of an organism to its environment, or the process by which it enhances such fitness. 2. The normal ability of the eye to adjust itself to variations in the intensity of light; the adjustment to such variations. 3. The decline in the frequency of firing of a neuron, particularly of a receptor, under conditions of constant stimulation. 4. In dentistry, (a) the proper fitting of a denture, (b) the degree of proximity and interlocking of restorative material to a tooth preparation, (C) the exact adjustment of bands to teeth. 5. In microbiology, the adjustment of bacterial physiology to a new environment. [EU] Adduct: Complex formed when a carcinogen combines with DNA or a protein. [NIH] Adenine: A purine base and a fundamental unit of adenine nucleotides. [NIH] Adenitis: Inflammation of a gland. [EU] Adenocarcinoma: A malignant epithelial tumor with a glandular organization. [NIH] Adenosine: A nucleoside that is composed of adenine and d-ribose. Adenosine or adenosine derivatives play many important biological roles in addition to being components of DNA and RNA. Adenosine itself is a neurotransmitter. [NIH] Adenosine Kinase: An enzyme that catalyzes the formation of ADP plus AMP from adenosine plus ATP. It can serve as a salvage mechanism for returning adenosine to nucleic acids. EC 2.7.1.20. [NIH] Adenosine Triphosphate: Adenosine 5'-(tetrahydrogen triphosphate). An adenine nucleotide containing three phosphate groups esterified to the sugar moiety. In addition to its crucial roles in metabolism adenosine triphosphate is a neurotransmitter. [NIH] Adenosylmethionine Decarboxylase: An enzyme that catalyzes the decarboxylation of Sadenosyl-L-methionine to yield 5'-deoxy-(5'-),3-aminopropyl-(1), methylsulfonium salt. It is one of the enzymes responsible for the synthesis of spermidine from putrescine. EC 4.1.1.50. [NIH]

Adenovirus: A group of viruses that cause respiratory tract and eye infections. Adenoviruses used in gene therapy are altered to carry a specific tumor-fighting gene. [NIH] Adenylate Cyclase: An enzyme of the lyase class that catalyzes the formation of cyclic AMP and pyrophosphate from ATP. EC 4.6.1.1. [NIH] Adjustment: The dynamic process wherein the thoughts, feelings, behavior, and biophysiological mechanisms of the individual continually change to adjust to the environment. [NIH] Adjuvant: A substance which aids another, such as an auxiliary remedy; in immunology, nonspecific stimulator (e.g., BCG vaccine) of the immune response. [EU] Adrenal Medulla: The inner part of the adrenal gland; it synthesizes, stores and releases catecholamines. [NIH] Adrenergic: Activated by, characteristic of, or secreting epinephrine or substances with similar activity; the term is applied to those nerve fibres that liberate norepinephrine at a synapse when a nerve impulse passes, i.e., the sympathetic fibres. [EU] Adsorption: The condensation of gases, liquids, or dissolved substances on the surfaces of solids. It includes adsorptive phenomena of bacteria and viruses as well as of tissues treated with exogenous drugs and chemicals. [NIH] Adsorptive: It captures volatile compounds by binding them to agents such as activated carbon or adsorptive resins. [NIH] Adverse Effect: An unwanted side effect of treatment. [NIH]

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Aerobic: In biochemistry, reactions that need oxygen to happen or happen when oxygen is present. [NIH] Aetiology: Study of the causes of disease. [EU] Affinity: 1. Inherent likeness or relationship. 2. A special attraction for a specific element, organ, or structure. 3. Chemical affinity; the force that binds atoms in molecules; the tendency of substances to combine by chemical reaction. 4. The strength of noncovalent chemical binding between two substances as measured by the dissociation constant of the complex. 5. In immunology, a thermodynamic expression of the strength of interaction between a single antigen-binding site and a single antigenic determinant (and thus of the stereochemical compatibility between them), most accurately applied to interactions among simple, uniform antigenic determinants such as haptens. Expressed as the association constant (K litres mole -1), which, owing to the heterogeneity of affinities in a population of antibody molecules of a given specificity, actually represents an average value (mean intrinsic association constant). 6. The reciprocal of the dissociation constant. [EU] Affinity Chromatography: In affinity chromatography, a ligand attached to a column binds specifically to the molecule to be purified. [NIH] Agar: A complex sulfated polymer of galactose units, extracted from Gelidium cartilagineum, Gracilaria confervoides, and related red algae. It is used as a gel in the preparation of solid culture media for microorganisms, as a bulk laxative, in making emulsions, and as a supporting medium for immunodiffusion and immunoelectrophoresis. [NIH]

Age Groups: Persons classified by age from birth (infant, newborn) to octogenarians and older (aged, 80 and over). [NIH] Aged, 80 and Over: A person 80 years of age and older. [NIH] Agonist: In anatomy, a prime mover. In pharmacology, a drug that has affinity for and stimulates physiologic activity at cell receptors normally stimulated by naturally occurring substances. [EU] Alanine: A non-essential amino acid that occurs in high levels in its free state in plasma. It is produced from pyruvate by transamination. It is involved in sugar and acid metabolism, increases immunity, and provides energy for muscle tissue, brain, and the central nervous system. [NIH] Alanine Racemase: A pyridoxal-phosphate protein that reversibly catalyzes the conversion of L-alanine to D-alanine. EC 5.1.1.1. [NIH] Albumin: 1. Any protein that is soluble in water and moderately concentrated salt solutions and is coagulable by heat. 2. Serum albumin; the major plasma protein (approximately 60 per cent of the total), which is responsible for much of the plasma colloidal osmotic pressure and serves as a transport protein carrying large organic anions, such as fatty acids, bilirubin, and many drugs, and also carrying certain hormones, such as cortisol and thyroxine, when their specific binding globulins are saturated. Albumin is synthesized in the liver. Low serum levels occur in protein malnutrition, active inflammation and serious hepatic and renal disease. [EU] Alertness: A state of readiness to detect and respond to certain specified small changes occurring at random intervals in the environment. [NIH] Alfalfa: A deep-rooted European leguminous plant (Medicago sativa) widely grown for hay and forage. [NIH] Algorithms: A procedure consisting of a sequence of algebraic formulas and/or logical steps to calculate or determine a given task. [NIH]

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Alkaline: Having the reactions of an alkali. [EU] Alkaline Phosphatase: An enzyme that catalyzes the conversion of an orthophosphoric monoester and water to an alcohol and orthophosphate. EC 3.1.3.1. [NIH] Alkylating Agents: Highly reactive chemicals that introduce alkyl radicals into biologically active molecules and thereby prevent their proper functioning. Many are used as antineoplastic agents, but most are very toxic, with carcinogenic, mutagenic, teratogenic, and immunosuppressant actions. They have also been used as components in poison gases. [NIH]

Alkylation: The covalent bonding of an alkyl group to an organic compound. It can occur by a simple addition reaction or by substitution of another functional group. [NIH] Allergen: An antigenic substance capable of producing immediate-type hypersensitivity (allergy). [EU] Alpha Particles: Positively charged particles composed of two protons and two neutrons, i.e., helium nuclei, emitted during disintegration of very heavy isotopes; a beam of alpha particles or an alpha ray has very strong ionizing power, but weak penetrability. [NIH] Alpha-1: A protein with the property of inactivating proteolytic enzymes such as leucocyte collagenase and elastase. [NIH] Alpha-helices: One of the secondary element of protein. [NIH] Alternative medicine: Practices not generally recognized by the medical community as standard or conventional medical approaches and used instead of standard treatments. Alternative medicine includes the taking of dietary supplements, megadose vitamins, and herbal preparations; the drinking of special teas; and practices such as massage therapy, magnet therapy, spiritual healing, and meditation. [NIH] Amber: A yellowish fossil resin, the gum of several species of coniferous trees, found in the alluvial deposits of northeastern Germany. It is used in molecular biology in the analysis of organic matter fossilized in amber. [NIH] Amine: An organic compound containing nitrogen; any member of a group of chemical compounds formed from ammonia by replacement of one or more of the hydrogen atoms by organic (hydrocarbon) radicals. The amines are distinguished as primary, secondary, and tertiary, according to whether one, two, or three hydrogen atoms are replaced. The amines include allylamine, amylamine, ethylamine, methylamine, phenylamine, propylamine, and many other compounds. [EU] Amino Acid Sequence: The order of amino acids as they occur in a polypeptide chain. This is referred to as the primary structure of proteins. It is of fundamental importance in determining protein conformation. [NIH] Amino Acid Substitution: The naturally occurring or experimentally induced replacement of one or more amino acids in a protein with another. If a functionally equivalent amino acid is substituted, the protein may retain wild-type activity. Substitution may also diminish or eliminate protein function. Experimentally induced substitution is often used to study enzyme activities and binding site properties. [NIH] Amino Acids: Organic compounds that generally contain an amino (-NH2) and a carboxyl (COOH) group. Twenty alpha-amino acids are the subunits which are polymerized to form proteins. [NIH] Amino Acids: Organic compounds that generally contain an amino (-NH2) and a carboxyl (COOH) group. Twenty alpha-amino acids are the subunits which are polymerized to form proteins. [NIH] Aminolevulinic Acid: A compound produced from succinyl-CoA and glycine as an

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intermediate in heme synthesis. [NIH] Aminopeptidases: A subclass of exopeptidases that act on the free N terminus end of a polypeptide liberating a single amino acid residue. EC 3.4.11. [NIH] Amino-terminal: The end of a protein or polypeptide chain that contains a free amino group (-NH2). [NIH] Ammonia: A colorless alkaline gas. It is formed in the body during decomposition of organic materials during a large number of metabolically important reactions. [NIH] Amniotic Fluid: Amniotic cavity fluid which is produced by the amnion and fetal lungs and kidneys. [NIH] Amoxicillin: A broad-spectrum semisynthetic antibiotic similar to ampicillin except that its resistance to gastric acid permits higher serum levels with oral administration. [NIH] Ampicillin: Semi-synthetic derivative of penicillin that functions as an orally active broadspectrum antibiotic. [NIH] Amplification: The production of additional copies of a chromosomal DNA sequence, found as either intrachromosomal or extrachromosomal DNA. [NIH] Amylase: An enzyme that helps the body digest starches. [NIH] Anaerobic: 1. Lacking molecular oxygen. 2. Growing, living, or occurring in the absence of molecular oxygen; pertaining to an anaerobe. [EU] Anaesthesia: Loss of feeling or sensation. Although the term is used for loss of tactile sensibility, or of any of the other senses, it is applied especially to loss of the sensation of pain, as it is induced to permit performance of surgery or other painful procedures. [EU] Analog: In chemistry, a substance that is similar, but not identical, to another. [NIH] Analogous: Resembling or similar in some respects, as in function or appearance, but not in origin or development;. [EU] Anaphylatoxins: The family of peptides C3a, C4a, C5a, and C5a des-arginine produced in the serum during complement activation. They produce smooth muscle contraction, mast cell histamine release, affect platelet aggregation, and act as mediators of the local inflammatory process. The order of anaphylatoxin activity from strongest to weakest is C5a, C3a, C4a, and C5a des-arginine. The latter is the so-called "classical" anaphylatoxin but shows no spasmogenic activity though it contains some chemotactic ability. [NIH] Anatomical: Pertaining to anatomy, or to the structure of the organism. [EU] Androgens: A class of sex hormones associated with the development and maintenance of the secondary male sex characteristics, sperm induction, and sexual differentiation. In addition to increasing virility and libido, they also increase nitrogen and water retention and stimulate skeletal growth. [NIH] Anemia: A reduction in the number of circulating erythrocytes or in the quantity of hemoglobin. [NIH] Angiogenesis: Blood vessel formation. Tumor angiogenesis is the growth of blood vessels from surrounding tissue to a solid tumor. This is caused by the release of chemicals by the tumor. [NIH] Angiotensinogen: An alpha-globulin of which a fragment of 14 amino acids is converted by renin to angiotensin I, the inactive precursor of angiotensin II. It is a member of the serpin superfamily. [NIH] Animal model: An animal with a disease either the same as or like a disease in humans. Animal models are used to study the development and progression of diseases and to test new treatments before they are given to humans. Animals with transplanted human cancers

292 E. coli

or other tissues are called xenograft models. [NIH] Anionic: Pertaining to or containing an anion. [EU] Anions: Negatively charged atoms, radicals or groups of atoms which travel to the anode or positive pole during electrolysis. [NIH] Annealing: The spontaneous alignment of two single DNA strands to form a double helix. [NIH]

Anode: Electrode held at a positive potential with respect to a cathode. [NIH] Anorexia: Lack or loss of appetite for food. Appetite is psychologic, dependent on memory and associations. Anorexia can be brought about by unattractive food, surroundings, or company. [NIH] Antagonism: Interference with, or inhibition of, the growth of a living organism by another living organism, due either to creation of unfavorable conditions (e. g. exhaustion of food supplies) or to production of a specific antibiotic substance (e. g. penicillin). [NIH] Anthrax: An acute bacterial infection caused by ingestion of bacillus organisms. Carnivores may become infected from ingestion of infected carcasses. It is transmitted to humans by contact with infected animals or contaminated animal products. The most common form in humans is cutaneous anthrax. [NIH] Antibacterial: A substance that destroys bacteria or suppresses their growth or reproduction. [EU] Antibiotic: A drug used to treat infections caused by bacteria and other microorganisms. [NIH]

Antibodies: Immunoglobulin molecules having a specific amino acid sequence by virtue of which they interact only with the antigen that induced their synthesis in cells of the lymphoid series (especially plasma cells), or with an antigen closely related to it. [NIH] Antibody: A type of protein made by certain white blood cells in response to a foreign substance (antigen). Each antibody can bind to only a specific antigen. The purpose of this binding is to help destroy the antigen. Antibodies can work in several ways, depending on the nature of the antigen. Some antibodies destroy antigens directly. Others make it easier for white blood cells to destroy the antigen. [NIH] Anticoagulant: A drug that helps prevent blood clots from forming. Also called a blood thinner. [NIH] Anticodon: The sequential set of three nucleotides in transfer RNA that interacts with its complement in messenger RNA, the codon, during translation in the ribosome. [NIH] Anticonvulsant: An agent that prevents or relieves convulsions. [EU] Antifibrinolytic: Inhibiting fibrinolysis. [EU] Antigen: Any substance which is capable, under appropriate conditions, of inducing a specific immune response and of reacting with the products of that response, that is, with specific antibody or specifically sensitized T-lymphocytes, or both. Antigens may be soluble substances, such as toxins and foreign proteins, or particulate, such as bacteria and tissue cells; however, only the portion of the protein or polysaccharide molecule known as the antigenic determinant (q.v.) combines with antibody or a specific receptor on a lymphocyte. Abbreviated Ag. [EU] Antigen-Antibody Complex: The complex formed by the binding of antigen and antibody molecules. The deposition of large antigen-antibody complexes leading to tissue damage causes immune complex diseases. [NIH] Antigen-presenting cell: APC. A cell that shows antigen on its surface to other cells of the

Dictionary 293

immune system. This is an important part of an immune response. [NIH] Anti-infective: An agent that so acts. [EU] Anti-inflammatory: Having to do with reducing inflammation. [NIH] Antimetabolite: A chemical that is very similar to one required in a normal biochemical reaction in cells. Antimetabolites can stop or slow down the reaction. [NIH] Antimicrobial: Killing microorganisms, or suppressing their multiplication or growth. [EU] Antineoplastic: Inhibiting or preventing the development of neoplasms, checking the maturation and proliferation of malignant cells. [EU] Antineoplastic Agents: Substances that inhibit or prevent the proliferation of neoplasms. [NIH]

Antioxidant: A substance that prevents damage caused by free radicals. Free radicals are highly reactive chemicals that often contain oxygen. They are produced when molecules are split to give products that have unpaired electrons. This process is called oxidation. [NIH] Antiserum: The blood serum obtained from an animal after it has been immunized with a particular antigen. It will contain antibodies which are specific for that antigen as well as antibodies specific for any other antigen with which the animal has previously been immunized. [NIH] Antithrombotic: Preventing or interfering with the formation of thrombi; an agent that so acts. [EU] Antiviral: Destroying viruses or suppressing their replication. [EU] Anuria: Inability to form or excrete urine. [NIH] Anus: The opening of the rectum to the outside of the body. [NIH] Anxiety: Persistent feeling of dread, apprehension, and impending disaster. [NIH] Aperture: A natural hole of perforation, especially one in a bone. [NIH] Apolipoproteins: The protein components of lipoproteins which remain after the lipids to which the proteins are bound have been removed. They play an important role in lipid transport and metabolism. [NIH] Apoptosis: One of the two mechanisms by which cell death occurs (the other being the pathological process of necrosis). Apoptosis is the mechanism responsible for the physiological deletion of cells and appears to be intrinsically programmed. It is characterized by distinctive morphologic changes in the nucleus and cytoplasm, chromatin cleavage at regularly spaced sites, and the endonucleolytic cleavage of genomic DNA (DNA fragmentation) at internucleosomal sites. This mode of cell death serves as a balance to mitosis in regulating the size of animal tissues and in mediating pathologic processes associated with tumor growth. [NIH] Aqueous: Having to do with water. [NIH] Arachidonic Acid: An unsaturated, essential fatty acid. It is found in animal and human fat as well as in the liver, brain, and glandular organs, and is a constituent of animal phosphatides. It is formed by the synthesis from dietary linoleic acid and is a precursor in the biosynthesis of prostaglandins, thromboxanes, and leukotrienes. [NIH] Arginine: An essential amino acid that is physiologically active in the L-form. [NIH] Aromatase: An enzyme which converts androgens to estrogens by desaturating ring A of the steroid. This enzyme complex is located in the endoplasmic reticulum of estrogenproducing cells including ovaries, placenta, testicular Sertoli and Leydig cells, adipose, and brain tissues. The enzyme complex has two components, one of which is the CYP19 gene

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product, the aromatase cytochrome P-450. The other component is NADPH-cytochrome P450 reductase which transfers reducing equivalents to P-450(arom). EC 1.14.13.-. [NIH] Aromatic: Having a spicy odour. [EU] Arterial: Pertaining to an artery or to the arteries. [EU] Arteries: The vessels carrying blood away from the heart. [NIH] Arterioles: The smallest divisions of the arteries located between the muscular arteries and the capillaries. [NIH] Articular: Of or pertaining to a joint. [EU] Ascites: Accumulation or retention of free fluid within the peritoneal cavity. [NIH] Asparaginase: A hydrolase enzyme that converts L-asparagine and water to L-aspartate and NH3. EC 3.5.1.1. [NIH] Aspartate: A synthetic amino acid. [NIH] Assay: Determination of the amount of a particular constituent of a mixture, or of the biological or pharmacological potency of a drug. [EU] Asymptomatic: Having no signs or symptoms of disease. [NIH] Ataxia: Impairment of the ability to perform smoothly coordinated voluntary movements. This condition may affect the limbs, trunk, eyes, pharnyx, larnyx, and other structures. Ataxia may result from impaired sensory or motor function. Sensory ataxia may result from posterior column injury or peripheral nerve diseases. Motor ataxia may be associated with cerebellar diseases; cerebral cortex diseases; thalamic diseases; basal ganglia diseases; injury to the red nucleus; and other conditions. [NIH] Atopic: Pertaining to an atopen or to atopy; allergic. [EU] ATP: ATP an abbreviation for adenosine triphosphate, a compound which serves as a carrier of energy for cells. [NIH] Atrophy: Decrease in the size of a cell, tissue, organ, or multiple organs, associated with a variety of pathological conditions such as abnormal cellular changes, ischemia, malnutrition, or hormonal changes. [NIH] Attenuated: Strain with weakened or reduced virulence. [NIH] Attenuation: Reduction of transmitted sound energy or its electrical equivalent. [NIH] Autacoids: A chemically diverse group of substances produced by various tissues in the body that cause slow contraction of smooth muscle; they have other intense but varied pharmacologic activities. [NIH] Autoantibodies: Antibodies that react with self-antigens (autoantigens) of the organism that produced them. [NIH] Autoantigens: Endogenous tissue constituents that have the ability to interact with autoantibodies and cause an immune response. [NIH] Autoimmune disease: A condition in which the body recognizes its own tissues as foreign and directs an immune response against them. [NIH] Autoimmunity: Process whereby the immune system reacts against the body's own tissues. Autoimmunity may produce or be caused by autoimmune diseases. [NIH] Autologous: Taken from an individual's own tissues, cells, or DNA. [NIH] Autologous bone marrow transplantation: A procedure in which bone marrow is removed from a person, stored, and then given back to the person after intensive treatment. [NIH] Autolysis: The spontaneous disintegration of tissues or cells by the action of their own

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autogenous enzymes. [NIH] Autonomic: Self-controlling; functionally independent. [EU] Avian: A plasmodial infection in birds. [NIH] Avidity: The strength of the interaction of an antiserum with a multivalent antigen. [NIH] Bacillus: A genus of Bacillaceae that are spore-forming, rod-shaped cells. Most species are saprophytic soil forms with only a few species being pathogenic. [NIH] Bacillus cereus: A species of rod-shaped bacteria that is a common soil saprophyte. Its spores are widespread and multiplication has been observed chiefly in foods. Contamination may lead to food poisoning. [NIH] Bacillus subtilis: A species of gram-positive bacteria that is a common soil and water saprophyte. [NIH] Bacteremia: The presence of viable bacteria circulating in the blood. Fever, chills, tachycardia, and tachypnea are common acute manifestations of bacteremia. The majority of cases are seen in already hospitalized patients, most of whom have underlying diseases or procedures which render their bloodstreams susceptible to invasion. [NIH] Bacteria: Unicellular prokaryotic microorganisms which generally possess rigid cell walls, multiply by cell division, and exhibit three principal forms: round or coccal, rodlike or bacillary, and spiral or spirochetal. [NIH] Bacterial Infections: Infections by bacteria, general or unspecified. [NIH] Bacterial Physiology: Physiological processes and activities of bacteria. [NIH] Bacterial Proteins: Proteins found in any species of bacterium. [NIH] Bacterial toxin: A toxic substance, made by bacteria, that can be modified to kill specific tumor cells without harming normal cells. [NIH] Bacterial Vaccines: Suspensions of attenuated or killed bacteria administered for the prevention or treatment of infectious bacterial disease. [NIH] Bactericidal: Substance lethal to bacteria; substance capable of killing bacteria. [NIH] Bacteriocins: Substances elaborated by specific strains of bacteria that are lethal against other strains of the same or related species. They are protein or lipopolysaccharide-protein complexes used in taxonomy studies of bacteria. [NIH] Bacteriolysis: Rupture of bacterial cells due to mechanical force, chemical action, or the lytic growth of bacteriophages. [NIH] Bacteriophage: A virus whose host is a bacterial cell; A virus that exclusively infects bacteria. It generally has a protein coat surrounding the genome (DNA or RNA). One of the coliphages most extensively studied is the lambda phage, which is also one of the most important. [NIH] Bacteriophage lambda: A temperate inducible phage and type species of the genus lambdalike Phages, in the family Siphoviridae. Its natural host is E. coli K12. Its virion contains linear double-stranded DNA, except for 12 complementary bases at the 5'-termini of the polynucleotide chains. The DNA circularizes on infection. [NIH] Bacteriostatic: 1. Inhibiting the growth or multiplication of bacteria. 2. An agent that inhibits the growth or multiplication of bacteria. [EU] Bacterium: Microscopic organism which may have a spherical, rod-like, or spiral unicellular or non-cellular body. Bacteria usually reproduce through asexual processes. [NIH] Bacteriuria: The presence of bacteria in the urine with or without consequent urinary tract infection. Since bacteriuria is a clinical entity, the term does not preclude the use of

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urine/microbiology for technical discussions on the isolation and segregation of bacteria in the urine. [NIH] Basal Ganglia: Large subcortical nuclear masses derived from the telencephalon and located in the basal regions of the cerebral hemispheres. [NIH] Basal Ganglia Diseases: Diseases of the basal ganglia including the putamen; globus pallidus; claustrum; amygdala; and caudate nucleus. Dyskinesias (most notably involuntary movements and alterations of the rate of movement) represent the primary clinical manifestations of these disorders. Common etiologies include cerebrovascular disease; neurodegenerative diseases; and craniocerebral trauma. [NIH] Base: In chemistry, the nonacid part of a salt; a substance that combines with acids to form salts; a substance that dissociates to give hydroxide ions in aqueous solutions; a substance whose molecule or ion can combine with a proton (hydrogen ion); a substance capable of donating a pair of electrons (to an acid) for the formation of a coordinate covalent bond. [EU] Base Sequence: The sequence of purines and pyrimidines in nucleic acids and polynucleotides. It is also called nucleotide or nucleoside sequence. [NIH] Basophil: A type of white blood cell. Basophils are granulocytes. [NIH] Benzene: Toxic, volatile, flammable liquid hydrocarbon biproduct of coal distillation. It is used as an industrial solvent in paints, varnishes, lacquer thinners, gasoline, etc. Benzene causes central nervous system damage acutely and bone marrow damage chronically and is carcinogenic. It was formerly used as parasiticide. [NIH] Beta-Galactosidase: A group of enzymes that catalyzes the hydrolysis of terminal, nonreducing beta-D-galactose residues in beta-galactosides. Deficiency of beta-Galactosidase A1 may cause gangliodisosis GM1. EC 3.2.1.23. [NIH] Beta-Lactamases: Enzymes found in many bacteria which catalyze the hydrolysis of the amide bond in the beta-lactam ring. Well known antibiotics destroyed by these enzymes are penicillins and cephalosporins. EC 3.5.2.6. [NIH] Bifidobacterium: A rod-shaped, gram-positive, non-acid-fast, non-spore-forming, nonmotile bacterium that is a genus of the family Actinomycetaceae. It inhabits the intestines and feces of humans as well as the human vagina. [NIH] Bile: An emulsifying agent produced in the liver and secreted into the duodenum. Its composition includes bile acids and salts, cholesterol, and electrolytes. It aids digestion of fats in the duodenum. [NIH] Bile Acids: Acids made by the liver that work with bile to break down fats. [NIH] Bile Acids and Salts: Steroid acids and salts. The primary bile acids are derived from cholesterol in the liver and usually conjugated with glycine or taurine. The secondary bile acids are further modified by bacteria in the intestine. They play an important role in the digestion and absorption of fat. They have also been used pharmacologically, especially in the treatment of gallstones. [NIH] Bile Ducts: Tubes that carry bile from the liver to the gallbladder for storage and to the small intestine for use in digestion. [NIH] Bile Pigments: Pigments that give a characteristic color to bile including: bilirubin, biliverdine, and bilicyanin. [NIH] Bilirubin: A bile pigment that is a degradation product of heme. [NIH] Binding Sites: The reactive parts of a macromolecule that directly participate in its specific combination with another molecule. [NIH] Biochemical: Relating to biochemistry; characterized by, produced by, or involving

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chemical reactions in living organisms. [EU] Biochemical reactions: In living cells, chemical reactions that help sustain life and allow cells to grow. [NIH] Biogenesis: The origin of life. It includes studies of the potential basis for life in organic compounds but excludes studies of the development of altered forms of life through mutation and natural selection, which is evolution. [NIH] Biological response modifier: BRM. A substance that stimulates the body's response to infection and disease. [NIH] Biological therapy: Treatment to stimulate or restore the ability of the immune system to fight infection and disease. Also used to lessen side effects that may be caused by some cancer treatments. Also known as immunotherapy, biotherapy, or biological response modifier (BRM) therapy. [NIH] Bioluminescence: The emission of light by living organisms such as the firefly, certain mollusks, beetles, fish, bacteria, fungi and protozoa. [NIH] Biomass: Total mass of all the organisms of a given type and/or in a given area. (From Concise Dictionary of Biology, 1990) It includes the yield of vegetative mass produced from any given crop. [NIH] Biophysics: The science of physical phenomena and processes in living organisms. [NIH] Biopolymers: Polymers, such as proteins, DNA, RNA, or polysaccharides formed by any living organism. [NIH] Biopsy: Removal and pathologic examination of specimens in the form of small pieces of tissue from the living body. [NIH] Biopsy specimen: Tissue removed from the body and examined under a microscope to determine whether disease is present. [NIH] Biosynthesis: The building up of a chemical compound in the physiologic processes of a living organism. [EU] Biotechnology: Body of knowledge related to the use of organisms, cells or cell-derived constituents for the purpose of developing products which are technically, scientifically and clinically useful. Alteration of biologic function at the molecular level (i.e., genetic engineering) is a central focus; laboratory methods used include transfection and cloning technologies, sequence and structure analysis algorithms, computer databases, and gene and protein structure function analysis and prediction. [NIH] Bioterrorism: The use of biological agents in terrorism. This includes the malevolent use of bacteria, viruses, or toxins against people, animals, or plants. [NIH] Biotin: Hexahydro-2-oxo-1H-thieno(3,4-d)imidazole-4-pentanoic acid. Growth factor present in minute amounts in every living cell. It occurs mainly bound to proteins or polypeptides and is abundant in liver, kidney, pancreas, yeast, and milk.The biotin content of cancerous tissue is higher than that of normal tissue. [NIH] Bivalent: Pertaining to a group of 2 homologous or partly homologous chromosomes during the zygotene stage of prophase to the first metaphase in meiosis. [NIH] Bladder: The organ that stores urine. [NIH] Bleomycin: A complex of related glycopeptide antibiotics from Streptomyces verticillus consisting of bleomycin A2 and B2. It inhibits DNA metabolism and is used as an antineoplastic, especially for solid tumors. [NIH] Bloating: Fullness or swelling in the abdomen that often occurs after meals. [NIH] Blood Cell Count: A count of the number of leukocytes and erythrocytes per unit volume in

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a sample of venous blood. A complete blood count (CBC) also includes measurement of the hemoglobin, hematocrit, and erythrocyte indices. [NIH] Blood Coagulation: The process of the interaction of blood coagulation factors that results in an insoluble fibrin clot. [NIH] Blood Glucose: Glucose in blood. [NIH] Blood Groups: The classification systems (or schemes) of the different antigens located on erythrocytes.The antigens are the phenotypic expression of the genetic differences characteristic of specific blood groups. [NIH] Blood Platelets: Non-nucleated disk-shaped cells formed in the megakaryocyte and found in the blood of all mammals. They are mainly involved in blood coagulation. [NIH] Blood pressure: The pressure of blood against the walls of a blood vessel or heart chamber. Unless there is reference to another location, such as the pulmonary artery or one of the heart chambers, it refers to the pressure in the systemic arteries, as measured, for example, in the forearm. [NIH] Blood vessel: A tube in the body through which blood circulates. Blood vessels include a network of arteries, arterioles, capillaries, venules, and veins. [NIH] Blood-Brain Barrier: Specialized non-fenestrated tightly-joined endothelial cells (tight junctions) that form a transport barrier for certain substances between the cerebral capillaries and the brain tissue. [NIH] Blot: To transfer DNA, RNA, or proteins to an immobilizing matrix such as nitrocellulose. [NIH]

Body Fluids: Liquid components of living organisms. [NIH] Bone Marrow: The soft tissue filling the cavities of bones. Bone marrow exists in two types, yellow and red. Yellow marrow is found in the large cavities of large bones and consists mostly of fat cells and a few primitive blood cells. Red marrow is a hematopoietic tissue and is the site of production of erythrocytes and granular leukocytes. Bone marrow is made up of a framework of connective tissue containing branching fibers with the frame being filled with marrow cells. [NIH] Bone Marrow Cells: Cells contained in the bone marrow including fat cells, stromal cells, megakaryocytes, and the immediate precursors of most blood cells. [NIH] Bone Marrow Purging: Techniques for the removal of subpopulations of cells (usually residual tumor cells) from the bone marrow ex vivo before it is infused. The purging is achieved by a variety of agents including pharmacologic agents, biophysical agents (laser photoirradiation or radioisotopes) and immunologic agents. Bone marrow purging is used in both autologous and allogeneic bone marrow transplantation. [NIH] Bowel: The long tube-shaped organ in the abdomen that completes the process of digestion. There is both a small and a large bowel. Also called the intestine. [NIH] Bowel Movement: Body wastes passed through the rectum and anus. [NIH] Brachial: All the nerves from the arm are ripped from the spinal cord. [NIH] Bradykinin: A nonapeptide messenger that is enzymatically produced from kallidin in the blood where it is a potent but short-lived agent of arteriolar dilation and increased capillary permeability. Bradykinin is also released from mast cells during asthma attacks, from gut walls as a gastrointestinal vasodilator, from damaged tissues as a pain signal, and may be a neurotransmitter. [NIH] Brain Neoplasms: Neoplasms of the intracranial components of the central nervous system, including the cerebral hemispheres, basal ganglia, hypothalamus, thalamus, brain stem, and

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cerebellum. Brain neoplasms are subdivided into primary (originating from brain tissue) and secondary (i.e., metastatic) forms. Primary neoplasms are subdivided into benign and malignant forms. In general, brain tumors may also be classified by age of onset, histologic type, or presenting location in the brain. [NIH] Branch: Most commonly used for branches of nerves, but applied also to other structures. [NIH]

Breakdown: A physical, metal, or nervous collapse. [NIH] Breeding: The science or art of changing the constitution of a population of plants or animals through sexual reproduction. [NIH] Broad-spectrum: Effective against a wide range of microorganisms; said of an antibiotic. [EU] Bromine: A halogen with the atomic symbol Br, atomic number 36, and atomic weight 79.904. It is a volatile reddish-brown liquid that gives off suffocating vapors, is corrosive to the skin, and may cause severe gastroenteritis if ingested. [NIH] Bronchial: Pertaining to one or more bronchi. [EU] Buccal: Pertaining to or directed toward the cheek. In dental anatomy, used to refer to the buccal surface of a tooth. [EU] Butyric Acid: A four carbon acid, CH3CH2CH2COOH, with an unpleasant odor that occurs in butter and animal fat as the glycerol ester. [NIH] Bypass: A surgical procedure in which the doctor creates a new pathway for the flow of body fluids. [NIH] Caesarean section: A surgical incision through the abdominal and uterine walls in order to deliver a baby. [NIH] Caffeine: A methylxanthine naturally occurring in some beverages and also used as a pharmacological agent. Caffeine's most notable pharmacological effect is as a central nervous system stimulant, increasing alertness and producing agitation. It also relaxes smooth muscle, stimulates cardiac muscle, stimulates diuresis, and appears to be useful in the treatment of some types of headache. Several cellular actions of caffeine have been observed, but it is not entirely clear how each contributes to its pharmacological profile. Among the most important are inhibition of cyclic nucleotide phosphodiesterases, antagonism of adenosine receptors, and modulation of intracellular calcium handling. [NIH] Calcium: A basic element found in nearly all organized tissues. It is a member of the alkaline earth family of metals with the atomic symbol Ca, atomic number 20, and atomic weight 40. Calcium is the most abundant mineral in the body and combines with phosphorus to form calcium phosphate in the bones and teeth. It is essential for the normal functioning of nerves and muscles and plays a role in blood coagulation (as factor IV) and in many enzymatic processes. [NIH] Calicivirus: A genus in the family Caliciviridae containing many species including feline calicivirus , vesicular exanthema of swine virus, and San Miguel sea lion viruses. [NIH] Capillary: Any one of the minute vessels that connect the arterioles and venules, forming a network in nearly all parts of the body. Their walls act as semipermeable membranes for the interchange of various substances, including fluids, between the blood and tissue fluid; called also vas capillare. [EU] Capsid: The outer protein protective shell of a virus, which protects the viral nucleic acid. [NIH]

Capsular: Cataract which is initiated by an opacification at the surface of the lens. [NIH] Carbohydrate: An aldehyde or ketone derivative of a polyhydric alcohol, particularly of the pentahydric and hexahydric alcohols. They are so named because the hydrogen and oxygen

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are usually in the proportion to form water, (CH2O)n. The most important carbohydrates are the starches, sugars, celluloses, and gums. They are classified into mono-, di-, tri-, polyand heterosaccharides. [EU] Carbon Dioxide: A colorless, odorless gas that can be formed by the body and is necessary for the respiration cycle of plants and animals. [NIH] Carcinogen: Any substance that causes cancer. [NIH] Carcinogenic: Producing carcinoma. [EU] Carcinoma: Cancer that begins in the skin or in tissues that line or cover internal organs. [NIH]

Cardiac: Having to do with the heart. [NIH] Cardiovascular: Having to do with the heart and blood vessels. [NIH] Cardiovascular disease: Any abnormal condition characterized by dysfunction of the heart and blood vessels. CVD includes atherosclerosis (especially coronary heart disease, which can lead to heart attacks), cerebrovascular disease (e.g., stroke), and hypertension (high blood pressure). [NIH] Carotene: The general name for a group of pigments found in green, yellow, and leafy vegetables, and yellow fruits. The pigments are fat-soluble, unsaturated aliphatic hydrocarbons functioning as provitamins and are converted to vitamin A through enzymatic processes in the intestinal wall. [NIH] Case report: A detailed report of the diagnosis, treatment, and follow-up of an individual patient. Case reports also contain some demographic information about the patient (for example, age, gender, ethnic origin). [NIH] Catabolism: Any destructive metabolic process by which organisms convert substances into excreted compounds. [EU] Catalytic Domain: The region of an enzyme that interacts with its substrate to cause the enzymatic reaction. [NIH] Cations: Postively charged atoms, radicals or groups of atoms which travel to the cathode or negative pole during electrolysis. [NIH] Causal: Pertaining to a cause; directed against a cause. [EU] Cause of Death: Factors which produce cessation of all vital bodily functions. They can be analyzed from an epidemiologic viewpoint. [NIH] CEA: Carcinoembryonic antigen. A substance that is sometimes found in an increased amount in the blood of people with certain cancers. [NIH] Cecum: The beginning of the large intestine. The cecum is connected to the lower part of the small intestine, called the ileum. [NIH] Cell: The individual unit that makes up all of the tissues of the body. All living things are made up of one or more cells. [NIH] Cell Cycle: The complex series of phenomena, occurring between the end of one cell division and the end of the next, by which cellular material is divided between daughter cells. [NIH] Cell Death: The termination of the cell's ability to carry out vital functions such as metabolism, growth, reproduction, responsiveness, and adaptability. [NIH] Cell Differentiation: Progressive restriction of the developmental potential and increasing specialization of function which takes place during the development of the embryo and leads to the formation of specialized cells, tissues, and organs. [NIH]

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Cell Division: The fission of a cell. [NIH] Cell Extracts: Preparations of cell constituents or subcellular materials, isolates, or substances. [NIH] Cell membrane: Cell membrane = plasma membrane. The structure enveloping a cell, enclosing the cytoplasm, and forming a selective permeability barrier; it consists of lipids, proteins, and some carbohydrates, the lipids thought to form a bilayer in which integral proteins are embedded to varying degrees. [EU] Cell proliferation: An increase in the number of cells as a result of cell growth and cell division. [NIH] Cell Respiration: The metabolic process of all living cells (animal and plant) in which oxygen is used to provide a source of energy for the cell. [NIH] Cell Size: The physical dimensions of a cell. It refers mainly to changes in dimensions correlated with physiological or pathological changes in cells. [NIH] Cell Survival: The span of viability of a cell characterized by the capacity to perform certain functions such as metabolism, growth, reproduction, some form of responsiveness, and adaptability. [NIH] Cellular metabolism: The sum of all chemical changes that take place in a cell through which energy and basic components are provided for essential processes, including the synthesis of new molecules and the breakdown and removal of others. [NIH] Cellulitis: An acute, diffuse, and suppurative inflammation of loose connective tissue, particularly the deep subcutaneous tissues, and sometimes muscle, which is most commonly seen as a result of infection of a wound, ulcer, or other skin lesions. [NIH] Cellulose: A polysaccharide with glucose units linked as in cellobiose. It is the chief constituent of plant fibers, cotton being the purest natural form of the substance. As a raw material, it forms the basis for many derivatives used in chromatography, ion exchange materials, explosives manufacturing, and pharmaceutical preparations. [NIH] Central Nervous System: The main information-processing organs of the nervous system, consisting of the brain, spinal cord, and meninges. [NIH] Central Nervous System Infections: Pathogenic infections of the brain, spinal cord, and meninges. DNA virus infections; RNA virus infections; bacterial infections; mycoplasma infections; Spirochaetales infections; fungal infections; protozoan infections; helminthiasis; and prion diseases may involve the central nervous system as a primary or secondary process. [NIH] Centromere: The clear constricted portion of the chromosome at which the chromatids are joined and by which the chromosome is attached to the spindle during cell division. [NIH] Cephalosporin Resistance: Non-susceptibility of an organism to the action of the cephalosporins. [NIH] Cephalosporins: A group of broad-spectrum antibiotics first isolated from the Mediterranean fungus Acremonium (Cephalosporium acremonium). They contain the betalactam moiety thia-azabicyclo-octenecarboxylic acid also called 7-aminocephalosporanic acid. [NIH] Cerebellar: Pertaining to the cerebellum. [EU] Cerebral: Of or pertaining of the cerebrum or the brain. [EU] Cerebral Infarction: The formation of an area of necrosis in the cerebrum caused by an insufficiency of arterial or venous blood flow. Infarcts of the cerebrum are generally classified by hemisphere (i.e., left vs. right), lobe (e.g., frontal lobe infarction), arterial

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distribution (e.g., infarction, anterior cerebral artery), and etiology (e.g., embolic infarction). [NIH]

Cerebral Palsy: Refers to a motor disability caused by a brain dysfunction. [NIH] Cerebrospinal: Pertaining to the brain and spinal cord. [EU] Cerebrospinal fluid: CSF. The fluid flowing around the brain and spinal cord. Cerebrospinal fluid is produced in the ventricles in the brain. [NIH] Cerebrovascular: Pertaining to the blood vessels of the cerebrum, or brain. [EU] Cerebrum: The largest part of the brain. It is divided into two hemispheres, or halves, called the cerebral hemispheres. The cerebrum controls muscle functions of the body and also controls speech, emotions, reading, writing, and learning. [NIH] Cervical: Relating to the neck, or to the neck of any organ or structure. Cervical lymph nodes are located in the neck; cervical cancer refers to cancer of the uterine cervix, which is the lower, narrow end (the "neck") of the uterus. [NIH] Cervix: The lower, narrow end of the uterus that forms a canal between the uterus and vagina. [NIH] Chaos: Complex behavior that seems random but actually has some hidden order. [NIH] Chemical Warfare: Tactical warfare using incendiary mixtures, smokes, or irritant, burning, or asphyxiating gases. [NIH] Chemical Warfare Agents: Chemicals that are used to cause the disturbance, disease, or death of humans during war. [NIH] Chemokines: Class of pro-inflammatory cytokines that have the ability to attract and activate leukocytes. They can be divided into at least three structural branches: C (Chemokines, C), CC (Chemokines, CC), and CXC (Chemokines, CXC), according to variations in a shared cysteine motif. [NIH] Chemotactic Factors: Chemical substances that attract or repel cells or organisms. The concept denotes especially those factors released as a result of tissue injury, invasion, or immunologic activity, that attract leukocytes, macrophages, or other cells to the site of infection or insult. [NIH] Chemotaxis: The movement of cells or organisms toward or away from a substance in response to its concentration gradient. [NIH] Chemotherapy: Treatment with anticancer drugs. [NIH] Chlorine: A greenish-yellow, diatomic gas that is a member of the halogen family of elements. It has the atomic symbol Cl, atomic number 17, and atomic weight 70.906. It is a powerful irritant that can cause fatal pulmonary edema. Chlorine is used in manufacturing, as a reagent in synthetic chemistry, for water purification, and in the production of chlorinated lime, which is used in fabric bleaching. [NIH] Chlorophyll: Porphyrin derivatives containing magnesium that act to convert light energy in photosynthetic organisms. [NIH] Chloroplasts: Plant cell inclusion bodies that contain the photosynthetic pigment chlorophyll, which is associated with the membrane of thylakoids. Chloroplasts occur in cells of leaves and young stems of higher plants. [NIH] Cholera: An acute diarrheal disease endemic in India and Southeast Asia whose causative agent is vibrio cholerae. This condition can lead to severe dehydration in a matter of hours unless quickly treated. [NIH] Cholera Toxin: The enterotoxin from Vibrio cholerae. It is a protein that consists of two major components, the heavy (H) or A peptide and the light (L) or B peptide or

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choleragenoid. The B peptide anchors the protein to intestinal epithelial cells, while the A peptide, enters the cytoplasm, and activates adenylate cyclase, and production of cAMP. Increased levels of cAMP are thought to modulate release of fluid and electrolytes from intestinal crypt cells. [NIH] Cholesterol: The principal sterol of all higher animals, distributed in body tissues, especially the brain and spinal cord, and in animal fats and oils. [NIH] Cholesterol Esters: Fatty acid esters of cholesterol which constitute about two-thirds of the cholesterol in the plasma. The accumulation of cholesterol esters in the arterial intima is a characteristic feature of atherosclerosis. [NIH] Chromatin: The material of chromosomes. It is a complex of DNA, histones, and nonhistone proteins (Chromosomal proteins, non-histone) found within the nucleus of a cell. [NIH] Chromosomal: Pertaining to chromosomes. [EU] Chromosome: Part of a cell that contains genetic information. Except for sperm and eggs, all human cells contain 46 chromosomes. [NIH] Chromosome Segregation: The orderly segregation of chromosomes during meiosis or mitosis. [NIH] Chronic: A disease or condition that persists or progresses over a long period of time. [NIH] Chronic renal: Slow and progressive loss of kidney function over several years, often resulting in end-stage renal disease. People with end-stage renal disease need dialysis or transplantation to replace the work of the kidneys. [NIH] Chylomicrons: A class of lipoproteins that carry dietary cholesterol and triglycerides from the small intestines to the tissues. [NIH] Chymopapain: A cysteine endopeptidase isolated from papaya latex. Preferential cleavage at glutamic and aspartic acid residues. EC 3.4.22.6. [NIH] Chymotrypsin: A serine endopeptidase secreted by the pancreas as its zymogen, chymotrypsinogen and carried in the pancreatic juice to the duodenum where it is activated by trypsin. It selectively cleaves aromatic amino acids on the carboxyl side. [NIH] Ciprofloxacin: A carboxyfluoroquinoline antimicrobial agent that is effective against a wide range of microorganisms. It has been successfully and safely used in the treatment of resistant respiratory, skin, bone, joint, gastrointestinal, urinary, and genital infections. [NIH] CIS: Cancer Information Service. The CIS is the National Cancer Institute's link to the public, interpreting and explaining research findings in a clear and understandable manner, and providing personalized responses to specific questions about cancer. Access the CIS by calling 1-800-4-CANCER, or by using the Web site at http://cis.nci.nih.gov. [NIH] Cisplatin: An inorganic and water-soluble platinum complex. After undergoing hydrolysis, it reacts with DNA to produce both intra and interstrand crosslinks. These crosslinks appear to impair replication and transcription of DNA. The cytotoxicity of cisplatin correlates with cellular arrest in the G2 phase of the cell cycle. [NIH] Citric Acid: A key intermediate in metabolism. It is an acid compound found in citrus fruits. The salts of citric acid (Citrates) can be used as anticoagulants due to their calcium chelating ability. [NIH] Clear cell carcinoma: A rare type of tumor of the female genital tract in which the inside of the cells looks clear when viewed under a microscope. [NIH] Cleave: A double-stranded cut in DNA with a restriction endonuclease. [NIH] Clinical Medicine: The study and practice of medicine by direct examination of the patient. [NIH]

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Clinical trial: A research study that tests how well new medical treatments or other interventions work in people. Each study is designed to test new methods of screening, prevention, diagnosis, or treatment of a disease. [NIH] Clone: The term "clone" has acquired a new meaning. It is applied specifically to the bits of inserted foreign DNA in the hybrid molecules of the population. Each inserted segment originally resided in the DNA of a complex genome amid millions of other DNA segment. [NIH]

Cloning: The production of a number of genetically identical individuals; in genetic engineering, a process for the efficient replication of a great number of identical DNA molecules. [NIH] Coagulation: 1. The process of clot formation. 2. In colloid chemistry, the solidification of a sol into a gelatinous mass; an alteration of a disperse phase or of a dissolved solid which causes the separation of the system into a liquid phase and an insoluble mass called the clot or curd. Coagulation is usually irreversible. 3. In surgery, the disruption of tissue by physical means to form an amorphous residuum, as in electrocoagulation and photocoagulation. [EU] Coal: A natural fuel formed by partial decomposition of vegetable matter under certain environmental conditions. [NIH] Cobalt: A trace element that is a component of vitamin B12. It has the atomic symbol Co, atomic number 27, and atomic weight 58.93. It is used in nuclear weapons, alloys, and pigments. Deficiency in animals leads to anemia; its excess in humans can lead to erythrocytosis. [NIH] Cod Liver Oil: Oil obtained from fresh livers of the cod family, Gadidae. It is a source of vitamins A and D. [NIH] Codon: A set of three nucleotides in a protein coding sequence that specifies individual amino acids or a termination signal (Codon, terminator). Most codons are universal, but some organisms do not produce the transfer RNAs (RNA, transfer) complementary to all codons. These codons are referred to as unassigned codons (Codons, nonsense). [NIH] Coenzyme: An organic nonprotein molecule, frequently a phosphorylated derivative of a water-soluble vitamin, that binds with the protein molecule (apoenzyme) to form the active enzyme (holoenzyme). [EU] Cofactor: A substance, microorganism or environmental factor that activates or enhances the action of another entity such as a disease-causing agent. [NIH] Coliphages: Viruses whose host is Escherichia coli. [NIH] Colitis: Inflammation of the colon. [NIH] Collagen: A polypeptide substance comprising about one third of the total protein in mammalian organisms. It is the main constituent of skin, connective tissue, and the organic substance of bones and teeth. Different forms of collagen are produced in the body but all consist of three alpha-polypeptide chains arranged in a triple helix. Collagen is differentiated from other fibrous proteins, such as elastin, by the content of proline, hydroxyproline, and hydroxylysine; by the absence of tryptophan; and particularly by the high content of polar groups which are responsible for its swelling properties. [NIH] Collagenous Colitis: A type of colitis. Caused by an abnormal band of collagen, a threadlike protein. [NIH] Collapse: 1. A state of extreme prostration and depression, with failure of circulation. 2. Abnormal falling in of the walls of any part of organ. [EU] Colloidal: Of the nature of a colloid. [EU]

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Colony-Stimulating Factors: Glycoproteins found in a subfraction of normal mammalian plasma and urine. They stimulate the proliferation of bone marrow cells in agar cultures and the formation of colonies of granulocytes and/or macrophages. The factors include interleukin-3 (IL-3), granulocyte colony-stimulating factor (G-CSF), macrophage colonystimulating factor (M-CSF), and granulocyte-macrophage colony-stimulating factor (GMCSF). [NIH] Colorectal: Having to do with the colon or the rectum. [NIH] Colorectal Cancer: Cancer that occurs in the colon (large intestine) or the rectum (the end of the large intestine). A number of digestive diseases may increase a person's risk of colorectal cancer, including polyposis and Zollinger-Ellison Syndrome. [NIH] Colostrum: The thin, yellow, serous fluid secreted by the mammary glands during pregnancy and immediately postpartum before lactation begins. It consists of immunologically active substances, white blood cells, water, protein, fat, and carbohydrates. [NIH]

Commensal: 1. Living on or within another organism, and deriving benefit without injuring or benefiting the other individual. 2. An organism living on or within another, but not causing injury to the host. [EU] Complement: A term originally used to refer to the heat-labile factor in serum that causes immune cytolysis, the lysis of antibody-coated cells, and now referring to the entire functionally related system comprising at least 20 distinct serum proteins that is the effector not only of immune cytolysis but also of other biologic functions. Complement activation occurs by two different sequences, the classic and alternative pathways. The proteins of the classic pathway are termed 'components of complement' and are designated by the symbols C1 through C9. C1 is a calcium-dependent complex of three distinct proteins C1q, C1r and C1s. The proteins of the alternative pathway (Collectively referred to as the properdin system) and complement regulatory proteins are known by semisystematic or trivial names. Fragments resulting from proteolytic cleavage of complement proteins are designated with lower-case letter suffixes, e.g., C3a. Inactivated fragments may be designated with the suffix 'i', e.g. C3bi. Activated components or complexes with biological activity are designated by a bar over the symbol e.g. C1 or C4b,2a. The classic pathway is activated by the binding of C1 to classic pathway activators, primarily antigen-antibody complexes containing IgM, IgG1, IgG3; C1q binds to a single IgM molecule or two adjacent IgG molecules. The alternative pathway can be activated by IgA immune complexes and also by nonimmunologic materials including bacterial endotoxins, microbial polysaccharides, and cell walls. Activation of the classic pathway triggers an enzymatic cascade involving C1, C4, C2 and C3; activation of the alternative pathway triggers a cascade involving C3 and factors B, D and P. Both result in the cleavage of C5 and the formation of the membrane attack complex. Complement activation also results in the formation of many biologically active complement fragments that act as anaphylatoxins, opsonins, or chemotactic factors. [EU] Complementary and alternative medicine: CAM. Forms of treatment that are used in addition to (Complementary) or instead of (alternative) standard treatments. These practices are not considered standard medical approaches. CAM includes dietary supplements, megadose vitamins, herbal preparations, special teas, massage therapy, magnet therapy, spiritual healing, and meditation. [NIH] Complementary medicine: Practices not generally recognized by the medical community as standard or conventional medical approaches and used to enhance or complement the standard treatments. Complementary medicine includes the taking of dietary supplements, megadose vitamins, and herbal preparations; the drinking of special teas; and practices such as massage therapy, magnet therapy, spiritual healing, and meditation. [NIH]

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Complementation: The production of a wild-type phenotype when two different mutations are combined in a diploid or a heterokaryon and tested in trans-configuration. [NIH] Complete remission: The disappearance of all signs of cancer. Also called a complete response. [NIH] Computational Biology: A field of biology concerned with the development of techniques for the collection and manipulation of biological data, and the use of such data to make biological discoveries or predictions. This field encompasses all computational methods and theories applicable to molecular biology and areas of computer-based techniques for solving biological problems including manipulation of models and datasets. [NIH] Conception: The onset of pregnancy, marked by implantation of the blastocyst; the formation of a viable zygote. [EU] Condoms: A sheath that is worn over the penis during sexual behavior in order to prevent pregnancy or spread of sexually transmitted disease. [NIH] Cones: One type of specialized light-sensitive cells (photoreceptors) in the retina that provide sharp central vision and color vision. [NIH] Confusion: A mental state characterized by bewilderment, emotional disturbance, lack of clear thinking, and perceptual disorientation. [NIH] Congestion: Excessive or abnormal accumulation of blood in a part. [EU] Conjugated: Acting or operating as if joined; simultaneous. [EU] Conjugation: 1. The act of joining together or the state of being conjugated. 2. A sexual process seen in bacteria, ciliate protozoa, and certain fungi in which nuclear material is exchanged during the temporary fusion of two cells (Conjugants). In bacterial genetics a form of sexual reproduction in which a donor bacterium (male) contributes some, or all, of its DNA (in the form of a replicated set) to a recipient (female) which then incorporates differing genetic information into its own chromosome by recombination and passes the recombined set on to its progeny by replication. In ciliate protozoa, two conjugants of separate mating types exchange micronuclear material and then separate, each now being a fertilized cell. In certain fungi, the process involves fusion of two gametes, resulting in union of their nuclei and formation of a zygote. 3. In chemistry, the joining together of two compounds to produce another compound, such as the combination of a toxic product with some substance in the body to form a detoxified product, which is then eliminated. [EU] Connective Tissue: Tissue that supports and binds other tissues. It consists of connective tissue cells embedded in a large amount of extracellular matrix. [NIH] Connective Tissue: Tissue that supports and binds other tissues. It consists of connective tissue cells embedded in a large amount of extracellular matrix. [NIH] Consciousness: Sense of awareness of self and of the environment. [NIH] Constipation: Infrequent or difficult evacuation of feces. [NIH] Constriction: The act of constricting. [NIH] Consumption: Pulmonary tuberculosis. [NIH] Contamination: The soiling or pollution by inferior material, as by the introduction of organisms into a wound, or sewage into a stream. [EU] Contraindications: Any factor or sign that it is unwise to pursue a certain kind of action or treatment, e. g. giving a general anesthetic to a person with pneumonia. [NIH] Control group: In a clinical trial, the group that does not receive the new treatment being studied. This group is compared to the group that receives the new treatment, to see if the new treatment works. [NIH]

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Convulsions: A general term referring to sudden and often violent motor activity of cerebral or brainstem origin. Convulsions may also occur in the absence of an electrical cerebral discharge (e.g., in response to hypotension). [NIH] Coordination: Muscular or motor regulation or the harmonious cooperation of muscles or groups of muscles, in a complex action or series of actions. [NIH] Coproporphyrinogen Oxidase: One of the enzymes active in heme biosynthesis. It catalyzes the oxidative decarboxylation of coproporphyrinogen III to protoporphyrinogen III by the conversion of two propionic acid groups to two vinyl groups. It can act under both aerobic and anaerobic conditions. EC 1.3.3.3. [NIH] Coronary: Encircling in the manner of a crown; a term applied to vessels; nerves, ligaments, etc. The term usually denotes the arteries that supply the heart muscle and, by extension, a pathologic involvement of them. [EU] Coronary heart disease: A type of heart disease caused by narrowing of the coronary arteries that feed the heart, which needs a constant supply of oxygen and nutrients carried by the blood in the coronary arteries. When the coronary arteries become narrowed or clogged by fat and cholesterol deposits and cannot supply enough blood to the heart, CHD results. [NIH] Coronary Thrombosis: Presence of a thrombus in a coronary artery, often causing a myocardial infarction. [NIH] Corpuscle: A small mass or body; a sensory nerve end bulb; a cell, especially that of the blood or the lymph. [NIH] Cortex: The outer layer of an organ or other body structure, as distinguished from the internal substance. [EU] Cortical: Pertaining to or of the nature of a cortex or bark. [EU] Cortisol: A steroid hormone secreted by the adrenal cortex as part of the body's response to stress. [NIH] Cosmids: Plasmids containing at least one cos (Cohesive-end site) of phage lambda. They are used as cloning vehicles for the study of aberrant eukaryotic structural genes and also as genetic vectors for introducing the nucleic acid of transforming viruses into cultured cells. [NIH]

Craniocerebral Trauma: Traumatic injuries involving the cranium and intracranial structures (i.e., brain; cranial nerves; meninges; and other structures). Injuries may be classified by whether or not the skull is penetrated (i.e., penetrating vs. nonpenetrating) or whether there is an associated hemorrhage. [NIH] Crossing-over: The exchange of corresponding segments between chromatids of homologous chromosomes during meiosia, forming a chiasma. [NIH] Crowding: Behavior with respect to an excessive number of individuals, human or animal, in relation to available space. [NIH] Crystallization: The formation of crystals; conversion to a crystalline form. [EU] Cultural Characteristics: Those aspects or characteristics which identify a culture. [NIH] Culture Media: Any liquid or solid preparation made specifically for the growth, storage, or transport of microorganisms or other types of cells. The variety of media that exist allow for the culturing of specific microorganisms and cell types, such as differential media, selective media, test media, and defined media. Solid media consist of liquid media that have been solidified with an agent such as agar or gelatin. [NIH] Cultured cell line: Cells of a single type that have been grown in the laboratory for several

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generations (Cell divisions). [NIH] Cultured cells: Animal or human cells that are grown in the laboratory. [NIH] Curative: Tending to overcome disease and promote recovery. [EU] Cutaneous: Having to do with the skin. [NIH] Cyanobacteria: A subgroup of the oxygenic photosynthetic bacteria comprised of unicellular to multicellular photosynthetic bacteria possessing chlorophyll a and carrying out oxygenic photosynthesis. Cyanobacteria are the only known organisms capable of fixing both carbon dioxide (in the presence of light) and nitrogen. Formerly called blue-green algae, cyanobacteria were traditionally treated as algae. By the late 19th century, however, it was realized that the blue-green algae were unique and lacked the traditional nucleus and chloroplasts of the green and other algae. The comparison of nucleotide base sequence data from 16S and 5S rRNA indicates that cyanobacteria represent a moderately deep phylogenetic unit within the gram-negative bacteria. [NIH] Cyclic: Pertaining to or occurring in a cycle or cycles; the term is applied to chemical compounds that contain a ring of atoms in the nucleus. [EU] Cyclospora: A genus of coccidian parasites in the family Eimeriidae. Cyclospora cayetanensis is pathogenic in humans, probably transmitted via the fecal-oral route, and causes nausea and diarrhea. [NIH] Cystamine: A radiation-protective agent that interferes with sulfhydryl enzymes. It may also protect against carbon tetrachloride liver damage. [NIH] Cysteamine: A radiation-protective agent that oxidizes in air to form cystamine. It can be given intravenously or orally to treat radiation sickness. The bitartrate has been used for the oral treatment of nephropathic cystinosis. [NIH] Cysteine: A thiol-containing non-essential amino acid that is oxidized to form cystine. [NIH] Cystine: A covalently linked dimeric nonessential amino acid formed by the oxidation of cysteine. Two molecules of cysteine are joined together by a disulfide bridge to form cystine. [NIH]

Cystitis: Inflammation of the urinary bladder. [EU] Cytochrome: Any electron transfer hemoprotein having a mode of action in which the transfer of a single electron is effected by a reversible valence change of the central iron atom of the heme prosthetic group between the +2 and +3 oxidation states; classified as cytochromes a in which the heme contains a formyl side chain, cytochromes b, which contain protoheme or a closely similar heme that is not covalently bound to the protein, cytochromes c in which protoheme or other heme is covalently bound to the protein, and cytochromes d in which the iron-tetrapyrrole has fewer conjugated double bonds than the hemes have. Well-known cytochromes have been numbered consecutively within groups and are designated by subscripts (beginning with no subscript), e.g. cytochromes c, c1, C2, . New cytochromes are named according to the wavelength in nanometres of the absorption maximum of the a-band of the iron (II) form in pyridine, e.g., c-555. [EU] Cytogenetics: A branch of genetics which deals with the cytological and molecular behavior of genes and chromosomes during cell division. [NIH] Cytokine: Small but highly potent protein that modulates the activity of many cell types, including T and B cells. [NIH] Cytokinesis: Division of the rest of cell. [NIH] Cytoplasm: The protoplasm of a cell exclusive of that of the nucleus; it consists of a continuous aqueous solution (Cytosol) and the organelles and inclusions suspended in it (phaneroplasm), and is the site of most of the chemical activities of the cell. [EU]

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Cytosine: A pyrimidine base that is a fundamental unit of nucleic acids. [NIH] Cytoskeleton: The network of filaments, tubules, and interconnecting filamentous bridges which give shape, structure, and organization to the cytoplasm. [NIH] Cytostatic: An agent that suppresses cell growth and multiplication. [EU] Cytotoxic: Cell-killing. [NIH] Cytotoxicity: Quality of being capable of producing a specific toxic action upon cells of special organs. [NIH] Cytotoxins: Substances elaborated by microorganisms, plants or animals that are specifically toxic to individual cells; they may be involved in immunity or may be contained in venoms. [NIH]

Dairy Products: Raw and processed or manufactured milk and milk-derived products. These are usually from cows (bovine) but are also from goats, sheep, reindeer, and water buffalo. [NIH] Databases, Bibliographic: Extensive collections, reputedly complete, of references and citations to books, articles, publications, etc., generally on a single subject or specialized subject area. Databases can operate through automated files, libraries, or computer disks. The concept should be differentiated from factual databases which is used for collections of data and facts apart from bibliographic references to them. [NIH] Daunorubicin: Very toxic anthracycline aminoglycoside antibiotic isolated from Streptomyces peucetius and others, used in treatment of leukemias and other neoplasms. [NIH]

Day Care: Institutional health care of patients during the day. The patients return home at night. [NIH] De novo: In cancer, the first occurrence of cancer in the body. [NIH] Deamination: The removal of an amino group (NH2) from a chemical compound. [NIH] Decarboxylation: The removal of a carboxyl group, usually in the form of carbon dioxide, from a chemical compound. [NIH] Decontamination: The removal of contaminating material, such as radioactive materials, biological materials, or chemical warfare agents, from a person or object. [NIH] Defense Mechanisms: Unconscious process used by an individual or a group of individuals in order to cope with impulses, feelings or ideas which are not acceptable at their conscious level; various types include reaction formation, projection and self reversal. [NIH] Degenerative: Undergoing degeneration : tending to degenerate; having the character of or involving degeneration; causing or tending to cause degeneration. [EU] Dehydration: The condition that results from excessive loss of body water. [NIH] Deletion: A genetic rearrangement through loss of segments of DNA (Chromosomes), bringing sequences, which are normally separated, into close proximity. [NIH] Dementia: An acquired organic mental disorder with loss of intellectual abilities of sufficient severity to interfere with social or occupational functioning. The dysfunction is multifaceted and involves memory, behavior, personality, judgment, attention, spatial relations, language, abstract thought, and other executive functions. The intellectual decline is usually progressive, and initially spares the level of consciousness. [NIH] Demethylation: Process that releases substantial amounts of carbon dioxide in the liver. [NIH]

Denaturation: Rupture of the hydrogen bonds by heating a DNA solution and then cooling it rapidly causes the two complementary strands to separate. [NIH]

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Dendrites: Extensions of the nerve cell body. They are short and branched and receive stimuli from other neurons. [NIH] Dendritic: 1. Branched like a tree. 2. Pertaining to or possessing dendrites. [EU] Dendritic cell: A special type of antigen-presenting cell (APC) that activates T lymphocytes. [NIH]

Density: The logarithm to the base 10 of the opacity of an exposed and processed film. [NIH] Deoxyribonucleic: A polymer of subunits called deoxyribonucleotides which is the primary genetic material of a cell, the material equivalent to genetic information. [NIH] Deoxyribonucleic acid: A polymer of subunits called deoxyribonucleotides which is the primary genetic material of a cell, the material equivalent to genetic information. [NIH] Deoxyribonucleotides: A purine or pyrimidine base bonded to a deoxyribose containing a bond to a phosphate group. [NIH] Depolarization: The process or act of neutralizing polarity. In neurophysiology, the reversal of the resting potential in excitable cell membranes when stimulated, i.e., the tendency of the cell membrane potential to become positive with respect to the potential outside the cell. [EU] Deprivation: Loss or absence of parts, organs, powers, or things that are needed. [EU] Depsipeptide: Anticancer drugs obtained from microorganisms. [NIH] Dermatitis: Any inflammation of the skin. [NIH] DES: Diethylstilbestrol. A synthetic hormone that was prescribed from the early 1940s until 1971 to help women with complications of pregnancy. DES has been linked to an increased risk of clear cell carcinoma of the vagina in daughters of women who used DES. DES may also increase the risk of breast cancer in women who used DES. [NIH] Desensitization: The prevention or reduction of immediate hypersensitivity reactions by administration of graded doses of allergen; called also hyposensitization and immunotherapy. [EU] Desiccation: Removal of moisture from a substance (Chemical, food, tissue, etc.). [NIH] Detoxification: Treatment designed to free an addict from his drug habit. [EU] Deuterium: Deuterium. The stable isotope of hydrogen. It has one neutron and one proton in the nucleus. [NIH] Developed Countries: Countries that have reached a level of economic achievement through an increase of production, per capita income and consumption, and utilization of natural and human resources. [NIH] Developing Countries: Countries in the process of change directed toward economic growth, that is, an increase in production, per capita consumption, and income. The process of economic growth involves better utilization of natural and human resources, which results in a change in the social, political, and economic structures. [NIH] Diabetes Mellitus: A heterogeneous group of disorders that share glucose intolerance in common. [NIH] Diagnostic procedure: A method used to identify a disease. [NIH] Diaphragm: The musculofibrous partition that separates the thoracic cavity from the abdominal cavity. Contraction of the diaphragm increases the volume of the thoracic cavity aiding inspiration. [NIH] Diarrhea: Passage of excessively liquid or excessively frequent stools. [NIH] Diarrhoea: Abnormal frequency and liquidity of faecal discharges. [EU]

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Diffusion: The tendency of a gas or solute to pass from a point of higher pressure or concentration to a point of lower pressure or concentration and to distribute itself throughout the available space; a major mechanism of biological transport. [NIH] Digestion: The process of breakdown of food for metabolism and use by the body. [NIH] Digestive system: The organs that take in food and turn it into products that the body can use to stay healthy. Waste products the body cannot use leave the body through bowel movements. The digestive system includes the salivary glands, mouth, esophagus, stomach, liver, pancreas, gallbladder, small and large intestines, and rectum. [NIH] Digestive tract: The organs through which food passes when food is eaten. These organs are the mouth, esophagus, stomach, small and large intestines, and rectum. [NIH] Dihydrotestosterone: Anabolic agent. [NIH] Dihydroxy: AMPA/Kainate antagonist. [NIH] Dilatation: The act of dilating. [NIH] Dilation: A process by which the pupil is temporarily enlarged with special eye drops (mydriatic); allows the eye care specialist to better view the inside of the eye. [NIH] Dimerization: The process by which two molecules of the same chemical composition form a condensation product or polymer. [NIH] Diploid: Having two sets of chromosomes. [NIH] Direct: 1. Straight; in a straight line. 2. Performed immediately and without the intervention of subsidiary means. [EU] Discrimination: The act of qualitative and/or quantitative differentiation between two or more stimuli. [NIH] Disinfectant: An agent that disinfects; applied particularly to agents used on inanimate objects. [EU] Dissociation: 1. The act of separating or state of being separated. 2. The separation of a molecule into two or more fragments (atoms, molecules, ions, or free radicals) produced by the absorption of light or thermal energy or by solvation. 3. In psychology, a defense mechanism in which a group of mental processes are segregated from the rest of a person's mental activity in order to avoid emotional distress, as in the dissociative disorders (q.v.), or in which an idea or object is segregated from its emotional significance; in the first sense it is roughly equivalent to splitting, in the second, to isolation. 4. A defect of mental integration in which one or more groups of mental processes become separated off from normal consciousness and, thus separated, function as a unitary whole. [EU] Dissociative Disorders: Sudden temporary alterations in the normally integrative functions of consciousness. [NIH] Disulfides: Chemical groups containing the covalent disulfide bonds -S-S-. The sulfur atoms can be bound to inorganic or organic moieties. [NIH] Disulphides: A covalent bridge formed by the oxidation of two cysteine residues to a cystine residue. The-S-S-bond is very strong and its presence confers additional stability. [NIH]

Dithiothreitol: A reagent commonly used in biochemical studies as a protective agent to prevent the oxidation of SH (thiol) groups and for reducing disulphides to dithiols. [NIH] Diuresis: Increased excretion of urine. [EU] Diuretic: A drug that increases the production of urine. [NIH] Dopamine: An endogenous catecholamine and prominent neurotransmitter in several

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systems of the brain. In the synthesis of catecholamines from tyrosine, it is the immediate precursor to norepinephrine and epinephrine. Dopamine is a major transmitter in the extrapyramidal system of the brain, and important in regulating movement. A family of dopaminergic receptor subtypes mediate its action. Dopamine is used pharmacologically for its direct (beta adrenergic agonist) and indirect (adrenergic releasing) sympathomimetic effects including its actions as an inotropic agent and as a renal vasodilator. [NIH] Doxorubicin: Antineoplastic antibiotic obtained from Streptomyces peucetics. It is a hydroxy derivative of daunorubicin and is used in treatment of both leukemia and solid tumors. [NIH] Drug Design: The molecular designing of drugs for specific purposes (such as DNAbinding, enzyme inhibition, anti-cancer efficacy, etc.) based on knowledge of molecular properties such as activity of functional groups, molecular geometry, and electronic structure, and also on information cataloged on analogous molecules. Drug design is generally computer-assisted molecular modeling and does not include pharmacokinetics, dosage analysis, or drug administration analysis. [NIH] Drug Interactions: The action of a drug that may affect the activity, metabolism, or toxicity of another drug. [NIH] Drug Resistance: Diminished or failed response of an organism, disease or tissue to the intended effectiveness of a chemical or drug. It should be differentiated from drug tolerance which is the progressive diminution of the susceptibility of a human or animal to the effects of a drug, as a result of continued administration. [NIH] Drug Tolerance: Progressive diminution of the susceptibility of a human or animal to the effects of a drug, resulting from its continued administration. It should be differentiated from drug resistance wherein an organism, disease, or tissue fails to respond to the intended effectiveness of a chemical or drug. It should also be differentiated from maximum tolerated dose and no-observed-adverse-effect level. [NIH] Duct: A tube through which body fluids pass. [NIH] Duodenum: The first part of the small intestine. [NIH] Dura mater: The outermost, toughest, and most fibrous of the three membranes (meninges) covering the brain and spinal cord; called also pachymeninx. [EU] Dyes: Chemical substances that are used to stain and color other materials. The coloring may or may not be permanent. Dyes can also be used as therapeutic agents and test reagents in medicine and scientific research. [NIH] Dysplasia: Cells that look abnormal under a microscope but are not cancer. [NIH] Dystrophy: Any disorder arising from defective or faulty nutrition, especially the muscular dystrophies. [EU] Edema: Excessive amount of watery fluid accumulated in the intercellular spaces, most commonly present in subcutaneous tissue. [NIH] Effector: It is often an enzyme that converts an inactive precursor molecule into an active second messenger. [NIH] Effector cell: A cell that performs a specific function in response to a stimulus; usually used to describe cells in the immune system. [NIH] Efficacy: The extent to which a specific intervention, procedure, regimen, or service produces a beneficial result under ideal conditions. Ideally, the determination of efficacy is based on the results of a randomized control trial. [NIH] Elective: Subject to the choice or decision of the patient or physician; applied to procedures

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that are advantageous to the patient but not urgent. [EU] Electrocoagulation: Electrosurgical procedures used to treat hemorrhage (e.g., bleeding ulcers) and to ablate tumors, mucosal lesions, and refractory arrhythmias. [NIH] Electrolysis: Destruction by passage of a galvanic electric current, as in disintegration of a chemical compound in solution. [NIH] Electrolyte: A substance that dissociates into ions when fused or in solution, and thus becomes capable of conducting electricity; an ionic solute. [EU] Electrons: Stable elementary particles having the smallest known negative charge, present in all elements; also called negatrons. Positively charged electrons are called positrons. The numbers, energies and arrangement of electrons around atomic nuclei determine the chemical identities of elements. Beams of electrons are called cathode rays or beta rays, the latter being a high-energy biproduct of nuclear decay. [NIH] Electrophoresis: An electrochemical process in which macromolecules or colloidal particles with a net electric charge migrate in a solution under the influence of an electric current. [NIH]

ELISA: A sensitive analytical technique in which an enzyme is complexed to an antigen or antibody. A substrate is then added which generates a color proportional to the amount of binding. This method can be adapted to a solid-phase technique. [NIH] Emaciation: Clinical manifestation of excessive leanness usually caused by disease or a lack of nutrition. [NIH] Embryo: The prenatal stage of mammalian development characterized by rapid morphological changes and the differentiation of basic structures. [NIH] Emollient: Softening or soothing; called also malactic. [EU] Empirical: A treatment based on an assumed diagnosis, prior to receiving confirmatory laboratory test results. [NIH] Emulsion: A preparation of one liquid distributed in small globules throughout the body of a second liquid. The dispersed liquid is the discontinuous phase, and the dispersion medium is the continuous phase. When oil is the dispersed liquid and an aqueous solution is the continuous phase, it is known as an oil-in-water emulsion, whereas when water or aqueous solution is the dispersed phase and oil or oleaginous substance is the continuous phase, it is known as a water-in-oil emulsion. Pharmaceutical emulsions for which official standards have been promulgated include cod liver oil emulsion, cod liver oil emulsion with malt, liquid petrolatum emulsion, and phenolphthalein in liquid petrolatum emulsion. [EU] Encephalitis: Inflammation of the brain due to infection, autoimmune processes, toxins, and other conditions. Viral infections (see encephalitis, viral) are a relatively frequent cause of this condition. [NIH] Endemic: Present or usually prevalent in a population or geographical area at all times; said of a disease or agent. Called also endemial. [EU] Endocarditis: Exudative and proliferative inflammatory alterations of the endocardium, characterized by the presence of vegetations on the surface of the endocardium or in the endocardium itself, and most commonly involving a heart valve, but sometimes affecting the inner lining of the cardiac chambers or the endocardium elsewhere. It may occur as a primary disorder or as a complication of or in association with another disease. [EU] Endocrine System: The system of glands that release their secretions (hormones) directly into the circulatory system. In addition to the endocrine glands, included are the chromaffin system and the neurosecretory systems. [NIH] Endonucleases: Enzymes that catalyze the hydrolysis of the internal bonds and thereby the

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formation of polynucleotides or oligonucleotides from ribo- or deoxyribonucleotide chains. EC 3.1.-. [NIH] Endothelial cell: The main type of cell found in the inside lining of blood vessels, lymph vessels, and the heart. [NIH] Endothelium: A layer of epithelium that lines the heart, blood vessels (endothelium, vascular), lymph vessels (endothelium, lymphatic), and the serous cavities of the body. [NIH] Endothelium, Lymphatic: Unbroken cellular lining (intima) of the lymph vessels (e.g., the high endothelial lymphatic venules). It is more permeable than vascular endothelium, lacking selective absorption and functioning mainly to remove plasma proteins that have filtered through the capillaries into the tissue spaces. [NIH] Endothelium, Vascular: Single pavement layer of cells which line the luminal surface of the entire vascular system and regulate the transport of macromolecules and blood components from interstitium to lumen; this function has been most intensively studied in the blood capillaries. [NIH] Endothelium-derived: Small molecule that diffuses to the adjacent muscle layer and relaxes it. [NIH] Endotoxin: Toxin from cell walls of bacteria. [NIH] End-stage renal: Total chronic kidney failure. When the kidneys fail, the body retains fluid and harmful wastes build up. A person with ESRD needs treatment to replace the work of the failed kidneys. [NIH] Enhancer: Transcriptional element in the virus genome. [NIH] Enteric bacteria: Single-celled microorganisms that lack chlorophyll. Some bacteria are capable of causing human, animal, or plant diseases; others are essential in pollution control because they break down organic matter in the air and in the water. [NIH] Enteric Nervous System: The entire nerve apparatus composed of the brain, spinal cord, nerves and ganglia. [NIH] Enteritis: Inflammation of the intestine, applied chiefly to inflammation of the small intestine; see also enterocolitis. [EU] Enterobactin: An iron-binding cyclic trimer of 2,3-dihydroxy-N-benzoyl-L-serine. It is produced by E. coli and other enteric bacteria. [NIH] Enterocolitis: Inflammation of the intestinal mucosa of the small and large bowel. [NIH] Enterocytes: Terminally differentiated cells comprising the majority of the external surface of the intestinal epithelium (see intestinal mucosa). Unlike goblet cells, they do not produce or secrete mucins, nor do they secrete cryptdins as do the paneth cells. [NIH] Enteropeptidase: A specialized proteolytic enzyme secreted by intestinal cells. It converts trypsinogen into its active form trypsin by removing the N-terminal peptide. EC 3.4.21.9. [NIH]

Enterotoxins: Substances that are toxic to the intestinal tract causing vomiting, diarrhea, etc.; most common enterotoxins are produced by bacteria. [NIH] Environmental Exposure: The exposure to potentially harmful chemical, physical, or biological agents in the environment or to environmental factors that may include ionizing radiation, pathogenic organisms, or toxic chemicals. [NIH] Environmental Health: The science of controlling or modifying those conditions, influences, or forces surrounding man which relate to promoting, establishing, and maintaining health. [NIH]

Enzymatic: Phase where enzyme cuts the precursor protein. [NIH]

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Enzyme: A protein that speeds up chemical reactions in the body. [NIH] Eosinophils: Granular leukocytes with a nucleus that usually has two lobes connected by a slender thread of chromatin, and cytoplasm containing coarse, round granules that are uniform in size and stainable by eosin. [NIH] Epidemic: Occurring suddenly in numbers clearly in excess of normal expectancy; said especially of infectious diseases but applied also to any disease, injury, or other healthrelated event occurring in such outbreaks. [EU] Epidemiological: Relating to, or involving epidemiology. [EU] Epidermal: Pertaining to or resembling epidermis. Called also epidermic or epidermoid. [EU] Epidermal Growth Factor: A 6 kD polypeptide growth factor initially discovered in mouse submaxillary glands. Human epidermal growth factor was originally isolated from urine based on its ability to inhibit gastric secretion and called urogastrone. epidermal growth factor exerts a wide variety of biological effects including the promotion of proliferation and differentiation of mesenchymal and epithelial cells. [NIH] Epidermis: Nonvascular layer of the skin. It is made up, from within outward, of five layers: 1) basal layer (stratum basale epidermidis); 2) spinous layer (stratum spinosum epidermidis); 3) granular layer (stratum granulosum epidermidis); 4) clear layer (stratum lucidum epidermidis); and 5) horny layer (stratum corneum epidermidis). [NIH] Epinephrine: The active sympathomimetic hormone from the adrenal medulla in most species. It stimulates both the alpha- and beta- adrenergic systems, causes systemic vasoconstriction and gastrointestinal relaxation, stimulates the heart, and dilates bronchi and cerebral vessels. It is used in asthma and cardiac failure and to delay absorption of local anesthetics. [NIH] Epithelial: Refers to the cells that line the internal and external surfaces of the body. [NIH] Epithelial Cells: Cells that line the inner and outer surfaces of the body. [NIH] Epithelium: One or more layers of epithelial cells, supported by the basal lamina, which covers the inner or outer surfaces of the body. [NIH] Epitope: A molecule or portion of a molecule capable of binding to the combining site of an antibody. For every given antigenic determinant, the body can construct a variety of antibody-combining sites, some of which fit almost perfectly, and others which barely fit. [NIH]

Erysipelas: An acute infection of the skin caused by species of streptococcus. This disease most frequently affects infants, young children, and the elderly. Characteristics include pink-to-red lesions that spread rapidly and are warm to the touch. The commonest site of involvement is the face. [NIH] Erythema: Redness of the skin produced by congestion of the capillaries. This condition may result from a variety of causes. [NIH] Erythrocyte Indices: Quantification of size and cell hemoglobin content or concentration of the erythrocyte, usually derived from erythrocyte count, blood hemoglobin concentration, and hematocrit. Includes the mean cell volume (MCV), mean cell hemoglobin (MCH), and mean cell hemoglobin concentration (MCHC). Use also for cell diameter and thickness. [NIH] Erythrocyte Membrane: The semipermeable outer portion of the red corpuscle. It is known as a 'ghost' after hemolysis. [NIH] Erythrocytes: Red blood cells. Mature erythrocytes are non-nucleated, biconcave disks containing hemoglobin whose function is to transport oxygen. [NIH] Erythromycin: A bacteriostatic antibiotic substance produced by Streptomyces erythreus.

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Erythromycin A is considered its major active component. In sensitive organisms, it inhibits protein synthesis by binding to 50S ribosomal subunits. This binding process inhibits peptidyl transferase activity and interferes with translocation of amino acids during translation and assembly of proteins. [NIH] Escherichia: A genus of gram-negative, facultatively anaerobic, rod-shaped bacteria whose organisms occur in the lower part of the intestine of warm-blooded animals. The species are either nonpathogenic or opportunistic pathogens. [NIH] Escherichia coli: A species of gram-negative, facultatively anaerobic, rod-shaped bacteria commonly found in the lower part of the intestine of warm-blooded animals. It is usually nonpathogenic, but some strains are known to produce diarrhea and pyogenic infections. [NIH]

Esophagus: The muscular tube through which food passes from the throat to the stomach. [NIH]

Essential Tremor: A rhythmic, involuntary, purposeless, oscillating movement resulting from the alternate contraction and relaxation of opposing groups of muscles. [NIH] Estrogen: One of the two female sex hormones. [NIH] Ethanol: A clear, colorless liquid rapidly absorbed from the gastrointestinal tract and distributed throughout the body. It has bactericidal activity and is used often as a topical disinfectant. It is widely used as a solvent and preservative in pharmaceutical preparations as well as serving as the primary ingredient in alcoholic beverages. [NIH] Ethionine: 2-Amino-4-(ethylthio)butyric acid. An antimetabolite and methionine antagonist that interferes with amino acid incorporation into proteins and with cellular ATP utilization. It also produces liver neoplasms. [NIH] Eukaryotic Cells: Cells of the higher organisms, containing a true nucleus bounded by a nuclear membrane. [NIH] Evacuation: An emptying, as of the bowels. [EU] Evoke: The electric response recorded from the cerebral cortex after stimulation of a peripheral sense organ. [NIH] Excipient: Any more or less inert substance added to a prescription in order to confer a suitable consistency or form to the drug; a vehicle. [EU] Excrete: To get rid of waste from the body. [NIH] Exfoliation: A falling off in scales or layers. [EU] Exhaustion: The feeling of weariness of mind and body. [NIH] Exogenous: Developed or originating outside the organism, as exogenous disease. [EU] Exonucleases: Enzymes that catalyze the release of mononucleotides by the hydrolysis of the terminal bond of deoxyribonucleotide or ribonucleotide chains. EC 3.1.-. [NIH] Exopeptidases: A sub-subclass of peptide hydrolases that act only near the ends of polypeptide chains. Exopeptidases are further divided into aminopeptidases, EC 3.4.11; dipeptidases, EC 3.4.13; dipeptidyl peptidases & tripeptidyl peptidases, EC 3.4.14; peptidyldipeptidases, EC 3.4.15; carboxypeptidases, EC 3.4.16 - EC 3.4.18, and omega peptidases, EC 3.4.19. EC 3.4.-. [NIH] Exoribonucleases: A family of enzymes that catalyze the exonucleolytic cleavage of RNA. It includes EC 3.1.13.-, EC 3.1.14.-, EC 3.1.15.-, and EC 3.1.16.-. EC 3.1.- [NIH] Expiration: The act of breathing out, or expelling air from the lungs. [EU] Extracellular: Outside a cell or cells. [EU]

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Extracellular Matrix: A meshwork-like substance found within the extracellular space and in association with the basement membrane of the cell surface. It promotes cellular proliferation and provides a supporting structure to which cells or cell lysates in culture dishes adhere. [NIH] Extracellular Matrix Proteins: Macromolecular organic compounds that contain carbon, hydrogen, oxygen, nitrogen, and usually, sulfur. These macromolecules (proteins) form an intricate meshwork in which cells are embedded to construct tissues. Variations in the relative types of macromolecules and their organization determine the type of extracellular matrix, each adapted to the functional requirements of the tissue. The two main classes of macromolecules that form the extracellular matrix are: glycosaminoglycans, usually linked to proteins (proteoglycans), and fibrous proteins (e.g., collagen, elastin, fibronectins and laminin). [NIH] Extraction: The process or act of pulling or drawing out. [EU] Extrarenal: Outside of the kidney. [EU] Extremity: A limb; an arm or leg (membrum); sometimes applied specifically to a hand or foot. [EU] Eye Infections: Infection, moderate to severe, caused by bacteria, fungi, or viruses, which occurs either on the external surface of the eye or intraocularly with probable inflammation, visual impairment, or blindness. [NIH] Faecal: Pertaining to or of the nature of feces. [EU] Family Planning: Programs or services designed to assist the family in controlling reproduction by either improving or diminishing fertility. [NIH] Fat: Total lipids including phospholipids. [NIH] Fatigue: The state of weariness following a period of exertion, mental or physical, characterized by a decreased capacity for work and reduced efficiency to respond to stimuli. [NIH]

Fatty acids: A major component of fats that are used by the body for energy and tissue development. [NIH] Feces: The excrement discharged from the intestines, consisting of bacteria, cells exfoliated from the intestines, secretions, chiefly of the liver, and a small amount of food residue. [EU] Fermentation: An enzyme-induced chemical change in organic compounds that takes place in the absence of oxygen. The change usually results in the production of ethanol or lactic acid, and the production of energy. [NIH] Ferrochelatase: An enzyme widely distributed in cells and tissues. It is located in the inner mitochondrial membrane and catalyzes the formation of heme from protoporphyrin IX and ferrous ions during the terminal step in the heme biosynthetic pathway. EC 4.99.1.1. [NIH] Fetus: The developing offspring from 7 to 8 weeks after conception until birth. [NIH] Fibrin: A protein derived from fibrinogen in the presence of thrombin, which forms part of the blood clot. [NIH] Fibrinogen: Plasma glycoprotein clotted by thrombin, composed of a dimer of three nonidentical pairs of polypeptide chains (alpha, beta, gamma) held together by disulfide bonds. Fibrinogen clotting is a sol-gel change involving complex molecular arrangements: whereas fibrinogen is cleaved by thrombin to form polypeptides A and B, the proteolytic action of other enzymes yields different fibrinogen degradation products. [NIH] Fibrinolysis: The natural enzymatic dissolution of fibrin. [NIH] Fibrinolytic: Pertaining to, characterized by, or causing the dissolution of fibrin by

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enzymatic action [EU] Fibroblast Growth Factor: Peptide isolated from the pituitary gland and from the brain. It is a potent mitogen which stimulates growth of a variety of mesodermal cells including chondrocytes, granulosa, and endothelial cells. The peptide may be active in wound healing and animal limb regeneration. [NIH] Fibroblasts: Connective tissue cells which secrete an extracellular matrix rich in collagen and other macromolecules. [NIH] Fibronectin: An adhesive glycoprotein. One form circulates in plasma, acting as an opsonin; another is a cell-surface protein which mediates cellular adhesive interactions. [NIH] Fibrosis: Any pathological condition where fibrous connective tissue invades any organ, usually as a consequence of inflammation or other injury. [NIH] Filtration: The passage of a liquid through a filter, accomplished by gravity, pressure, or vacuum (suction). [EU] Fixation: 1. The act or operation of holding, suturing, or fastening in a fixed position. 2. The condition of being held in a fixed position. 3. In psychiatry, a term with two related but distinct meanings : (1) arrest of development at a particular stage, which like regression (return to an earlier stage), if temporary is a normal reaction to setbacks and difficulties but if protracted or frequent is a cause of developmental failures and emotional problems, and (2) a close and suffocating attachment to another person, especially a childhood figure, such as one's mother or father. Both meanings are derived from psychoanalytic theory and refer to 'fixation' of libidinal energy either in a specific erogenous zone, hence fixation at the oral, anal, or phallic stage, or in a specific object, hence mother or father fixation. 4. The use of a fixative (q.v.) to preserve histological or cytological specimens. 5. In chemistry, the process whereby a substance is removed from the gaseous or solution phase and localized, as in carbon dioxide fixation or nitrogen fixation. 6. In ophthalmology, direction of the gaze so that the visual image of the object falls on the fovea centralis. 7. In film processing, the chemical removal of all undeveloped salts of the film emulsion, leaving only the developed silver to form a permanent image. [EU] Flatus: Gas passed through the rectum. [NIH] Fluorescence: The property of emitting radiation while being irradiated. The radiation emitted is usually of longer wavelength than that incident or absorbed, e.g., a substance can be irradiated with invisible radiation and emit visible light. X-ray fluorescence is used in diagnosis. [NIH] Fluorescent Antibody Technique: Test for tissue antigen using either a direct method by conjugation of antibody with fluorescent dye or an indirect method by formation of antigenantibody complex which is then labeled with fluorescein-conjugated anti-immunoglobulin antibody. The tissue is then examined by fluorescence microscopy. [NIH] Fluorouracil: A pyrimidine analog that acts as an antineoplastic antimetabolite and also has immunosuppressant. It interferes with DNA synthesis by blocking the thymidylate synthetase conversion of deoxyuridylic acid to thymidylic acid. [NIH] Fold: A plication or doubling of various parts of the body. [NIH] Follicles: Shafts through which hair grows. [NIH] Food Handling: Any aspect of the operations in the preparation, transport, storage, packaging, wrapping, exposure for sale, service, or delivery of food. [NIH] Foodborne Illness: An acute gastrointestinal infection caused by food that contains harmful bacteria. Symptoms include diarrhea, abdominal pain, fever, and chills. Also called food poisoning. [NIH]

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Frameshift: A type of mutation which causes out-of-phase transcription of the base sequence; such mutations arise from the addition or delection of nucleotide(s) in numbers other than 3 or multiples of 3. [NIH] Frameshift Mutation: A type of mutation in which a number of nucleotides not divisible by three is deleted from or inserted into a coding sequence, thereby causing an alteration in the reading frame of the entire sequence downstream of the mutation. These mutations may be induced by certain types of mutagens or may occur spontaneously. [NIH] Fructose: A type of sugar found in many fruits and vegetables and in honey. Fructose is used to sweeten some diet foods. It is considered a nutritive sweetener because it has calories. [NIH] Fungi: A kingdom of eukaryotic, heterotrophic organisms that live as saprobes or parasites, including mushrooms, yeasts, smuts, molds, etc. They reproduce either sexually or asexually, and have life cycles that range from simple to complex. Filamentous fungi refer to those that grow as multicelluar colonies (mushrooms and molds). [NIH] Fungus: A general term used to denote a group of eukaryotic protists, including mushrooms, yeasts, rusts, moulds, smuts, etc., which are characterized by the absence of chlorophyll and by the presence of a rigid cell wall composed of chitin, mannans, and sometimes cellulose. They are usually of simple morphological form or show some reversible cellular specialization, such as the formation of pseudoparenchymatous tissue in the fruiting body of a mushroom. The dimorphic fungi grow, according to environmental conditions, as moulds or yeasts. [EU] GABA: The most common inhibitory neurotransmitter in the central nervous system. [NIH] Galactosides: Glycosides formed by the reaction of the hydroxyl group on the anomeric carbon atom of galactose with an alcohol to form an acetal. They include both alpha- and beta-galactosides. [NIH] Gallbladder: The pear-shaped organ that sits below the liver. Bile is concentrated and stored in the gallbladder. [NIH] Gamma Rays: Very powerful and penetrating, high-energy electromagnetic radiation of shorter wavelength than that of x-rays. They are emitted by a decaying nucleus, usually between 0.01 and 10 MeV. They are also called nuclear x-rays. [NIH] Ganglia: Clusters of multipolar neurons surrounded by a capsule of loosely organized connective tissue located outside the central nervous system. [NIH] Gangrenous: A circumscribed, deep-seated, suppurative inflammation of the subcutaneous tissue of the eyelid discharging pus from several points. [NIH] Gas: Air that comes from normal breakdown of food. The gases are passed out of the body through the rectum (flatus) or the mouth (burp). [NIH] Gas Gangrene: A severe condition resulting from bacteria invading healthy muscle from adjacent traumatized muscle or soft tissue. The infection originates in a wound contaminated with bacteria of the genus Clostridium. C. perfringens accounts for the majority of cases (over eighty percent), while C. noyvi, C. septicum, and C. histolyticum cause most of the other cases. [NIH] Gasoline: Volative flammable fuel (liquid hydrocarbons) derived from crude petroleum by processes such as distillation reforming, polymerization, etc. [NIH] Gastric: Having to do with the stomach. [NIH] Gastric Acid: Hydrochloric acid present in gastric juice. [NIH] Gastrin: A hormone released after eating. Gastrin causes the stomach to produce more acid. [NIH]

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Gastroenteritis: An acute inflammation of the lining of the stomach and intestines, characterized by anorexia, nausea, diarrhoea, abdominal pain, and weakness, which has various causes, including food poisoning due to infection with such organisms as Escherichia coli, Staphylococcus aureus, and Salmonella species; consumption of irritating food or drink; or psychological factors such as anger, stress, and fear. Called also enterogastritis. [EU] Gastrointestinal: Refers to the stomach and intestines. [NIH] Gastrointestinal tract: The stomach and intestines. [NIH] Gelatin: A product formed from skin, white connective tissue, or bone collagen. It is used as a protein food adjuvant, plasma substitute, hemostatic, suspending agent in pharmaceutical preparations, and in the manufacturing of capsules and suppositories. [NIH] Gene: The functional and physical unit of heredity passed from parent to offspring. Genes are pieces of DNA, and most genes contain the information for making a specific protein. [NIH]

Gene Expression: The phenotypic manifestation of a gene or genes by the processes of gene action. [NIH] Gene Fusion: Fusion of structural genes to analyze protein behavior or fusion of regulatory sequences with structural genes to determine mechanisms of regulation. [NIH] Gene Library: A large collection of cloned DNA fragments from a given organism, tissue, organ, or cell type. It may contain complete genomic sequences (genomic library) or complementary DNA sequences, the latter being formed from messenger RNA and lacking intron sequences. [NIH] Genetic Code: The specifications for how information, stored in nucleic acid sequence (base sequence), is translated into protein sequence (amino acid sequence). The start, stop, and order of amino acids of a protein is specified by consecutive triplets of nucleotides called codons (Codon). [NIH] Genetic Engineering: Directed modification of the gene complement of a living organism by such techniques as altering the DNA, substituting genetic material by means of a virus, transplanting whole nuclei, transplanting cell hybrids, etc. [NIH] Genetic Techniques: Chromosomal, biochemical, intracellular, and other methods used in the study of genetics. [NIH] Genetic testing: Analyzing DNA to look for a genetic alteration that may indicate an increased risk for developing a specific disease or disorder. [NIH] Genetic Vectors: Any DNA molecule capable of autonomous replication within a host cell and into which other DNA sequences can be inserted and thus amplified. Many are derived from plasmids, bacteriophages or viruses. They are used for transporting foreign genes into recipient cells. Genetic vectors possess a functional replicator site and contain genetic markers to facilitate their selective recognition. [NIH] Genetics: The biological science that deals with the phenomena and mechanisms of heredity. [NIH] Genital: Pertaining to the genitalia. [EU] Genitourinary: Pertaining to the genital and urinary organs; urogenital; urinosexual. [EU] Genomic Library: A form of gene library containing the complete DNA sequences present in the genome of a given organism. It contrasts with a cDNA library which contains only sequences utilized in protein coding (lacking introns). [NIH] Genomics: The systematic study of the complete DNA sequences (genome) of organisms. [NIH]

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Genotype: The genetic constitution of the individual; the characterization of the genes. [NIH] Germ Cells: The reproductive cells in multicellular organisms. [NIH] Germ-free: Free of bacteria, disease-causing viruses, and other organisms that can cause infection. [NIH] Gland: An organ that produces and releases one or more substances for use in the body. Some glands produce fluids that affect tissues or organs. Others produce hormones or participate in blood production. [NIH] Glomerular: Pertaining to or of the nature of a glomerulus, especially a renal glomerulus. [EU]

Glomeruli: Plural of glomerulus. [NIH] Glomerulonephritis: Glomerular disease characterized by an inflammatory reaction, with leukocyte infiltration and cellular proliferation of the glomeruli, or that appears to be the result of immune glomerular injury. [NIH] Glucose: D-Glucose. A primary source of energy for living organisms. It is naturally occurring and is found in fruits and other parts of plants in its free state. It is used therapeutically in fluid and nutrient replacement. [NIH] Glucuronic Acid: Derivatives of uronic acid found throughout the plant and animal kingdoms. They detoxify drugs and toxins by conjugating with them to form glucuronides in the liver which are more water-soluble metabolites that can be easily eliminated from the body. [NIH] Glutamate: Excitatory neurotransmitter of the brain. [NIH] Glutamate Decarboxylase: A pyridoxal-phosphate protein that catalyzes the alphadecarboxylation of L-glutamic acid to form gamma-aminobutyric acid and carbon dioxide. The enzyme is found in bacteria and in invertebrate and vertebrate nervous systems. It is the rate-limiting enzyme in determining gaba levels in normal nervous tissues. The brain enzyme also acts on L-cysteate, L-cysteine sulfinate, and L-aspartate. EC 4.1.1.15. [NIH] Glutamic Acid: A non-essential amino acid naturally occurring in the L-form. Glutamic acid (glutamate) is the most common excitatory neurotransmitter in the central nervous system. [NIH]

Glutamine: A non-essential amino acid present abundantly throught the body and is involved in many metabolic processes. It is synthesized from glutamic acid and ammonia. It is the principal carrier of nitrogen in the body and is an important energy source for many cells. [NIH] Glutathione Peroxidase: An enzyme catalyzing the oxidation of 2 moles of glutathione in the presence of hydrogen peroxide to yield oxidized glutathione and water. EC 1.11.1.9. [NIH]

Glycerol: A trihydroxy sugar alcohol that is an intermediate in carbohydrate and lipid metabolism. It is used as a solvent, emollient, pharmaceutical agent, and sweetening agent. [NIH]

Glycerophospholipids: Derivatives of phosphatidic acid in which the hydrophobic regions are composed of two fatty acids and a polar alcohol is joined to the C-3 position of glycerol through a phosphodiester bond. They are named according to their polar head groups, such as phosphatidylcholine and phosphatidylethanolamine. [NIH] Glycine: A non-essential amino acid. It is found primarily in gelatin and silk fibroin and used therapeutically as a nutrient. It is also a fast inhibitory neurotransmitter. [NIH] Glycogen: A sugar stored in the liver and muscles. It releases glucose into the blood when cells need it for energy. Glycogen is the chief source of stored fuel in the body. [NIH]

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Glycophorin: The major sialoglycoprotein of the human erythrocyte membrane. It consists of at least two sialoglycopeptides and is composed of 60% carbohydrate including sialic acid and 40% protein. It is involved in a number of different biological activities including the binding of MN blood groups, influenza viruses, kidney bean phytohemagglutinin, and wheat germ agglutinin. [NIH] Glycoprotein: A protein that has sugar molecules attached to it. [NIH] Glycoside: Any compound that contains a carbohydrate molecule (sugar), particularly any such natural product in plants, convertible, by hydrolytic cleavage, into sugar and a nonsugar component (aglycone), and named specifically for the sugar contained, as glucoside (glucose), pentoside (pentose), fructoside (fructose) etc. [EU] Glycosidic: Formed by elimination of water between the anomeric hydroxyl of one sugar and a hydroxyl of another sugar molecule. [NIH] Goblet Cells: Cells of the epithelial lining that produce and secrete mucins. [NIH] Gonadal: Pertaining to a gonad. [EU] Governing Board: The group in which legal authority is vested for the control of healthrelated institutions and organizations. [NIH] Gp120: 120-kD HIV envelope glycoprotein which is involved in the binding of the virus to its membrane receptor, the CD4 molecule, found on the surface of certain cells in the body. [NIH]

GP41: 41-kD HIV transmembrane envelope glycoprotein which mediates the fusion of the viral membrane with the membrane of the target cell. [NIH] Graft: Healthy skin, bone, or other tissue taken from one part of the body and used to replace diseased or injured tissue removed from another part of the body. [NIH] Graft Rejection: An immune response with both cellular and humoral components, directed against an allogeneic transplant, whose tissue antigens are not compatible with those of the recipient. [NIH] Graft-versus-host disease: GVHD. A reaction of donated bone marrow or peripheral stem cells against a person's tissue. [NIH] Gram-negative: Losing the stain or decolorized by alcohol in Gram's method of staining, a primary characteristic of bacteria having a cell wall composed of a thin layer of peptidoglycan covered by an outer membrane of lipoprotein and lipopolysaccharide. [EU] Gram-Negative Bacteria: Bacteria which lose crystal violet stain but are stained pink when treated by Gram's method. [NIH] Gram-positive: Retaining the stain or resisting decolorization by alcohol in Gram's method of staining, a primary characteristic of bacteria whose cell wall is composed of a thick layer of peptidologlycan with attached teichoic acids. [EU] Gram-Positive Bacteria: Bacteria which retain the crystal violet stain when treated by Gram's method. [NIH] Granule: A small pill made from sucrose. [EU] Granulocyte Colony-Stimulating Factor: A glycoprotein of MW 25 kDa containing internal disulfide bonds. It induces the survival, proliferation, and differentiation of neutrophilic granulocyte precursor cells and functionally activates mature blood neutrophils. Among the family of colony-stimulating factors, G-CSF is the most potent inducer of terminal differentiation to granulocytes and macrophages of leukemic myeloid cell lines. [NIH] Granulocytes: Leukocytes with abundant granules in the cytoplasm. They are divided into three groups: neutrophils, eosinophils, and basophils. [NIH]

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Granulosa Cells: Cells of the membrana granulosa lining the vesicular ovarian follicle which become luteal cells after ovulation. [NIH] Growth: The progressive development of a living being or part of an organism from its earliest stage to maturity. [NIH] Growth factors: Substances made by the body that function to regulate cell division and cell survival. Some growth factors are also produced in the laboratory and used in biological therapy. [NIH] Growth Inhibitors: Endogenous or exogenous substances which inhibit the normal growth of human and animal cells or micro-organisms, as distinguished from those affecting plant growth (plant growth regulators). [NIH] Guanylate Cyclase: An enzyme that catalyzes the conversion of GTP to 3',5'-cyclic GMP and pyrophosphate. It also acts on ITP and dGTP. (From Enzyme Nomenclature, 1992) EC 4.6.1.2. [NIH] Gyrase: An enzyme that causes negative supercoiling of E. coli DNA during replication. [NIH]

Habitat: An area considered in terms of its environment, particularly as this determines the type and quality of the vegetation the area can carry. [NIH] Hair follicles: Shafts or openings on the surface of the skin through which hair grows. [NIH] Handwashing: The act of cleansing the hands with water or other liquid, with or without the inclusion of soap or other detergent, for the purpose of removing soil or microorganisms. [NIH] Haploid: An organism with one basic chromosome set, symbolized by n; the normal condition of gametes in diploids. [NIH] Haptens: Small antigenic determinants capable of eliciting an immune response only when coupled to a carrier. Haptens bind to antibodies but by themselves cannot elicit an antibody response. [NIH] Headache: Pain in the cranial region that may occur as an isolated and benign symptom or as a manifestation of a wide variety of conditions including subarachnoid hemorrhage; craniocerebral trauma; central nervous system infections; intracranial hypertension; and other disorders. In general, recurrent headaches that are not associated with a primary disease process are referred to as headache disorders (e.g., migraine). [NIH] Heart attack: A seizure of weak or abnormal functioning of the heart. [NIH] Heart failure: Loss of pumping ability by the heart, often accompanied by fatigue, breathlessness, and excess fluid accumulation in body tissues. [NIH] Hematocrit: Measurement of the volume of packed red cells in a blood specimen by centrifugation. The procedure is performed using a tube with graduated markings or with automated blood cell counters. It is used as an indicator of erythrocyte status in disease. For example, anemia shows a low hematocrit, polycythemia, high values. [NIH] Hematogenous: Originating in the blood or spread through the bloodstream. [NIH] Heme: The color-furnishing portion of hemoglobin. It is found free in tissues and as the prosthetic group in many hemeproteins. [NIH] Hemin: Chloro(7,12-diethenyl-3,8,13,17-tetramethyl-21H,23H-porphine-2,18dipropanoato(4-)-N(21),N(22),N(23),N(24)) ferrate(2-) dihydrogen. [NIH] Hemodialysis: The use of a machine to clean wastes from the blood after the kidneys have failed. The blood travels through tubes to a dialyzer, which removes wastes and extra fluid. The cleaned blood then flows through another set of tubes back into the body. [NIH]

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Hemoglobin: One of the fractions of glycosylated hemoglobin A1c. Glycosylated hemoglobin is formed when linkages of glucose and related monosaccharides bind to hemoglobin A and its concentration represents the average blood glucose level over the previous several weeks. HbA1c levels are used as a measure of long-term control of plasma glucose (normal, 4 to 6 percent). In controlled diabetes mellitus, the concentration of glycosylated hemoglobin A is within the normal range, but in uncontrolled cases the level may be 3 to 4 times the normal conentration. Generally, complications are substantially lower among patients with Hb levels of 7 percent or less than in patients with HbA1c levels of 9 percent or more. [NIH] Hemoglobinuria: The presence of free hemoglobin in the urine. [NIH] Hemolysis: The destruction of erythrocytes by many different causal agents such as antibodies, bacteria, chemicals, temperature, and changes in tonicity. [NIH] Hemolytic: A disease that affects the blood and blood vessels. It destroys red blood cells, cells that cause the blood to clot, and the lining of blood vessels. HUS is often caused by the Escherichia coli bacterium in contaminated food. People with HUS may develop acute renal failure. [NIH] Hemolytic-Uremic Syndrome: Syndrome of hemolytic anemia, thrombocytopenia, and acute renal failure, with pathological finding of thrombotic microangiopathy in kidney and renal cortical necrosis. [NIH] Hemorrhage: Bleeding or escape of blood from a vessel. [NIH] Heparin: Heparinic acid. A highly acidic mucopolysaccharide formed of equal parts of sulfated D-glucosamine and D-glucuronic acid with sulfaminic bridges. The molecular weight ranges from six to twenty thousand. Heparin occurs in and is obtained from liver, lung, mast cells, etc., of vertebrates. Its function is unknown, but it is used to prevent blood clotting in vivo and vitro, in the form of many different salts. [NIH] Hepatic: Refers to the liver. [NIH] Hepatitis: Inflammation of the liver and liver disease involving degenerative or necrotic alterations of hepatocytes. [NIH] Hepatocytes: The main structural component of the liver. They are specialized epithelial cells that are organized into interconnected plates called lobules. [NIH] Herbicide: A chemical that kills plants. [NIH] Hereditary: Of, relating to, or denoting factors that can be transmitted genetically from one generation to another. [NIH] Heredity: 1. The genetic transmission of a particular quality or trait from parent to offspring. 2. The genetic constitution of an individual. [EU] Herpes: Any inflammatory skin disease caused by a herpesvirus and characterized by the formation of clusters of small vesicles. When used alone, the term may refer to herpes simplex or to herpes zoster. [EU] Herpes virus: A member of the herpes family of viruses. [NIH] Herpes Zoster: Acute vesicular inflammation. [NIH] Heterodimers: Zippered pair of nonidentical proteins. [NIH] Heterogeneity: The property of one or more samples or populations which implies that they are not identical in respect of some or all of their parameters, e. g. heterogeneity of variance. [NIH]

Heterotrophic: Pertaining to organisms that are consumers and dependent on other organisms for their source of energy (food). [NIH]

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Histamine: 1H-Imidazole-4-ethanamine. A depressor amine derived by enzymatic decarboxylation of histidine. It is a powerful stimulant of gastric secretion, a constrictor of bronchial smooth muscle, a vasodilator, and also a centrally acting neurotransmitter. [NIH] Histidine: An essential amino acid important in a number of metabolic processes. It is required for the production of histamine. [NIH] Homeostasis: The processes whereby the internal environment of an organism tends to remain balanced and stable. [NIH] Homogenate: A suspension of animal tissue that is ground in the all-glass "homogenizer" described by Potter and Elvehjem in 1936. [NIH] Homogeneous: Consisting of or composed of similar elements or ingredients; of a uniform quality throughout. [EU] Homologous: Corresponding in structure, position, origin, etc., as (a) the feathers of a bird and the scales of a fish, (b) antigen and its specific antibody, (C) allelic chromosomes. [EU] Homotypic: Adhesion between neutrophils. [NIH] Hormonal: Pertaining to or of the nature of a hormone. [EU] Hormone: A substance in the body that regulates certain organs. Hormones such as gastrin help in breaking down food. Some hormones come from cells in the stomach and small intestine. [NIH] Horseradish Peroxidase: An enzyme isolated from horseradish which is able to act as an antigen. It is frequently used as a histochemical tracer for light and electron microscopy. Its antigenicity has permitted its use as a combined antigen and marker in experimental immunology. [NIH] Host: Any animal that receives a transplanted graft. [NIH] Human growth hormone: A protein hormone, secreted by the anterior lobe of the pituitary, which promotes growth of the whole body by stimulating protein synthesis. The human gene has already been cloned and successfully expressed in bacteria. [NIH] Human papillomavirus: HPV. A virus that causes abnormal tissue growth (warts) and is often associated with some types of cancer. [NIH] Humoral: Of, relating to, proceeding from, or involving a bodily humour - now often used of endocrine factors as opposed to neural or somatic. [EU] Humour: 1. A normal functioning fluid or semifluid of the body (as the blood, lymph or bile) especially of vertebrates. 2. A secretion that is itself an excitant of activity (as certain hormones). [EU] Hybrid: Cross fertilization between two varieties or, more usually, two species of vines, see also crossing. [NIH] Hybridization: The genetic process of crossbreeding to produce a hybrid. Hybrid nucleic acids can be formed by nucleic acid hybridization of DNA and RNA molecules. Protein hybridization allows for hybrid proteins to be formed from polypeptide chains. [NIH] Hydration: Combining with water. [NIH] Hydrocephalus: Excessive accumulation of cerebrospinal fluid within the cranium which may be associated with dilation of cerebral ventricles, intracranial hypertension; headache; lethargy; urinary incontinence; and ataxia (and in infants macrocephaly). This condition may be caused by obstruction of cerebrospinal fluid pathways due to neurologic abnormalities, intracranial hemorrhages; central nervous system infections; brain neoplasms; craniocerebral trauma; and other conditions. Impaired resorption of cerebrospinal fluid from the arachnoid villi results in a communicating form of

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hydrocephalus. Hydrocephalus ex-vacuo refers to ventricular dilation that occurs as a result of brain substance loss from cerebral infarction and other conditions. [NIH] Hydrogel: A network of cross-linked hydrophilic macromolecules used in biomedical applications. [NIH] Hydrogen: The first chemical element in the periodic table. It has the atomic symbol H, atomic number 1, and atomic weight 1. It exists, under normal conditions, as a colorless, odorless, tasteless, diatomic gas. Hydrogen ions are protons. Besides the common H1 isotope, hydrogen exists as the stable isotope deuterium and the unstable, radioactive isotope tritium. [NIH] Hydrogen Peroxide: A strong oxidizing agent used in aqueous solution as a ripening agent, bleach, and topical anti-infective. It is relatively unstable and solutions deteriorate over time unless stabilized by the addition of acetanilide or similar organic materials. [NIH] Hydrolases: Any member of the class of enzymes that catalyze the cleavage of the substrate and the addition of water to the resulting molecules, e.g., esterases, glycosidases (glycoside hydrolases), lipases, nucleotidases, peptidases (peptide hydrolases), and phosphatases (phosphoric monoester hydrolases). EC 3. [NIH] Hydrolysis: The process of cleaving a chemical compound by the addition of a molecule of water. [NIH] Hydrophilic: Readily absorbing moisture; hygroscopic; having strongly polar groups that readily interact with water. [EU] Hydrophobic: Not readily absorbing water, or being adversely affected by water, as a hydrophobic colloid. [EU] Hydroxylation: Hydroxylate, to introduce hydroxyl into (a compound or radical) usually by replacement of hydrogen. [EU] Hypercholesterolemia: Abnormally high levels of cholesterol in the blood. [NIH] Hypersensitivity: Altered reactivity to an antigen, which can result in pathologic reactions upon subsequent exposure to that particular antigen. [NIH] Hypertension: Persistently high arterial blood pressure. Currently accepted threshold levels are 140 mm Hg systolic and 90 mm Hg diastolic pressure. [NIH] Hypnotic: A drug that acts to induce sleep. [EU] Hypotension: Abnormally low blood pressure. [NIH] Hypoxanthine: A purine and a reaction intermediate in the metabolism of adenosine and in the formation of nucleic acids by the salvage pathway. [NIH] Id: The part of the personality structure which harbors the unconscious instinctive desires and strivings of the individual. [NIH] Idiopathic: Describes a disease of unknown cause. [NIH] Ileum: The lower end of the small intestine. [NIH] Imidazole: C3H4N2. The ring is present in polybenzimidazoles. [NIH] Immune Complex Diseases: Group of diseases mediated by the deposition of large soluble complexes of antigen and antibody with resultant damage to tissue. Besides serum sickness and the arthus reaction, evidence supports a pathogenic role for immune complexes in many other systemic immunologic diseases including glomerulonephritis, systemic lupus erythematosus and polyarteritis nodosa. [NIH] Immune function: Production and action of cells that fight disease or infection. [NIH] Immune response: The activity of the immune system against foreign substances (antigens).

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[NIH]

Immune Sera: Serum that contains antibodies. It is obtained from an animal that has been immunized either by antigen injection or infection with microorganisms containing the antigen. [NIH] Immune system: The organs, cells, and molecules responsible for the recognition and disposal of foreign ("non-self") material which enters the body. [NIH] Immune-response: The production of antibodies or particular types of cytotoxic lymphoid cells on challenge with an antigen. [NIH] Immunity: Nonsusceptibility to the invasive or pathogenic microorganisms or to the toxic effect of antigenic substances. [NIH]

effects

of

foreign

Immunization: Deliberate stimulation of the host's immune response. Active immunization involves administration of antigens or immunologic adjuvants. Passive immunization involves administration of immune sera or lymphocytes or their extracts (e.g., transfer factor, immune RNA) or transplantation of immunocompetent cell producing tissue (thymus or bone marrow). [NIH] Immunoassay: Immunochemical assay or detection of a substance by serologic or immunologic methods. Usually the substance being studied serves as antigen both in antibody production and in measurement of antibody by the test substance. [NIH] Immunocompromised: Having a weakened immune system caused by certain diseases or treatments. [NIH] Immunodeficiency: The decreased ability of the body to fight infection and disease. [NIH] Immunodeficiency syndrome: The inability of the body to produce an immune response. [NIH]

Immunofluorescence: A technique for identifying molecules present on the surfaces of cells or in tissues using a highly fluorescent substance coupled to a specific antibody. [NIH] Immunogenic: Producing immunity; evoking an immune response. [EU] Immunoglobulin: A protein that acts as an antibody. [NIH] Immunologic: The ability of the antibody-forming system to recall a previous experience with an antigen and to respond to a second exposure with the prompt production of large amounts of antibody. [NIH] Immunology: The study of the body's immune system. [NIH] Immunomagnetic Separation: A cell-separation technique where magnetizable microspheres or beads are first coated with monoclonal antibody, allowed to search and bind to target cells, and are then selectively removed when passed through a magnetic field. Among other applications, the technique is commonly used to remove tumor cells from the marrow (bone marrow purging) of patients who are to undergo autologous bone marrow transplantation. [NIH] Immunosuppressant: An agent capable of suppressing immune responses. [EU] Immunosuppressive: Describes the ability to lower immune system responses. [NIH] Immunosuppressive therapy: Therapy used to decrease the body's immune response, such as drugs given to prevent transplant rejection. [NIH] Immunotherapy: Manipulation of the host's immune system in treatment of disease. It includes both active and passive immunization as well as immunosuppressive therapy to prevent graft rejection. [NIH] Impairment: In the context of health experience, an impairment is any loss or abnormality of psychological, physiological, or anatomical structure or function. [NIH]

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Impetigo: A common superficial bacterial infection caused by staphylococcus aureus or group A beta-hemolytic streptococci. Characteristics include pustular lesions that rupture and discharge a thin, amber-colored fluid that dries and forms a crust. This condition is commonly located on the face, especially about the mouth and nose. [NIH] In situ: In the natural or normal place; confined to the site of origin without invasion of neighbouring tissues. [EU] In Situ Hybridization: A technique that localizes specific nucleic acid sequences within intact chromosomes, eukaryotic cells, or bacterial cells through the use of specific nucleic acid-labeled probes. [NIH] In vitro: In the laboratory (outside the body). The opposite of in vivo (in the body). [NIH] In vivo: In the body. The opposite of in vitro (outside the body or in the laboratory). [NIH] Incision: A cut made in the body during surgery. [NIH] Incontinence: Inability to control the flow of urine from the bladder (urinary incontinence) or the escape of stool from the rectum (fecal incontinence). [NIH] Incubated: Grown in the laboratory under controlled conditions. (For instance, white blood cells can be grown in special conditions so that they attack specific cancer cells when returned to the body.) [NIH] Incubation: The development of an infectious disease from the entrance of the pathogen to the appearance of clinical symptoms. [EU] Incubation period: The period of time likely to elapse between exposure to the agent of the disease and the onset of clinical symptoms. [NIH] Indicative: That indicates; that points out more or less exactly; that reveals fairly clearly. [EU] Induction: The act or process of inducing or causing to occur, especially the production of a specific morphogenetic effect in the developing embryo through the influence of evocators or organizers, or the production of anaesthesia or unconsciousness by use of appropriate agents. [EU] Induction therapy: Treatment designed to be used as a first step toward shrinking the cancer and in evaluating response to drugs and other agents. Induction therapy is followed by additional therapy to eliminate whatever cancer remains. [NIH] Infancy: The period of complete dependency prior to the acquisition of competence in walking, talking, and self-feeding. [NIH] Infant, Newborn: An infant during the first month after birth. [NIH] Infantile: Pertaining to an infant or to infancy. [EU] Infarction: A pathological process consisting of a sudden insufficient blood supply to an area, which results in necrosis of that area. It is usually caused by a thrombus, an embolus, or a vascular torsion. [NIH] Infection: 1. Invasion and multiplication of microorganisms in body tissues, which may be clinically unapparent or result in local cellular injury due to competitive metabolism, toxins, intracellular replication, or antigen-antibody response. The infection may remain localized, subclinical, and temporary if the body's defensive mechanisms are effective. A local infection may persist and spread by extension to become an acute, subacute, or chronic clinical infection or disease state. A local infection may also become systemic when the microorganisms gain access to the lymphatic or vascular system. 2. An infectious disease. [EU]

Infectious Bursal Disease Virus: A species of Avibirnavirus causing severe inflammation of the bursa of Fabricius in chickens and other fowl. Transmission is thought to be through

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contaminated feed or water. Vaccines have been used with varying degrees of success. [NIH] Infectious Diarrhea: Diarrhea caused by infection from bacteria, viruses, or parasites. [NIH] Infiltration: The diffusion or accumulation in a tissue or cells of substances not normal to it or in amounts of the normal. Also, the material so accumulated. [EU] Inflammation: A pathological process characterized by injury or destruction of tissues caused by a variety of cytologic and chemical reactions. It is usually manifested by typical signs of pain, heat, redness, swelling, and loss of function. [NIH] Inflammatory bowel disease: A general term that refers to the inflammation of the colon and rectum. Inflammatory bowel disease includes ulcerative colitis and Crohn's disease. [NIH]

Influenza: An acute viral infection involving the respiratory tract. It is marked by inflammation of the nasal mucosa, the pharynx, and conjunctiva, and by headache and severe, often generalized, myalgia. [NIH] Ingestion: Taking into the body by mouth [NIH] Inhalation: The drawing of air or other substances into the lungs. [EU] Inhibin: Glyceroprotein hormone produced in the seminiferous tubules by the Sertoli cells in the male and by the granulosa cells in the female follicles. The hormone inhibits FSH and LH synthesis and secretion by the pituitary cells thereby affecting sexual maturation and fertility. [NIH] Initiation: Mutation induced by a chemical reactive substance causing cell changes; being a step in a carcinogenic process. [NIH] Initiator: A chemically reactive substance which may cause cell changes if ingested, inhaled or absorbed into the body; the substance may thus initiate a carcinogenic process. [NIH] Inner ear: The labyrinth, comprising the vestibule, cochlea, and semicircular canals. [NIH] Inorganic: Pertaining to substances not of organic origin. [EU] Insecticides: Pesticides designed to control insects that are harmful to man. The insects may be directly harmful, as those acting as disease vectors, or indirectly harmful, as destroyers of crops, food products, or textile fabrics. [NIH] Insertional: A technique in which foreign DNA is cloned into a restriction site which occupies a position within the coding sequence of a gene in the cloning vector molecule. Insertion interrupts the gene's sequence such that its original function is no longer expressed. [NIH] Insight: The capacity to understand one's own motives, to be aware of one's own psychodynamics, to appreciate the meaning of symbolic behavior. [NIH] Insomnia: Difficulty in going to sleep or getting enough sleep. [NIH] Insulator: Material covering the metal conductor of the lead. It is usually polyurethane or silicone. [NIH] Insulin: A protein hormone secreted by beta cells of the pancreas. Insulin plays a major role in the regulation of glucose metabolism, generally promoting the cellular utilization of glucose. It is also an important regulator of protein and lipid metabolism. Insulin is used as a drug to control insulin-dependent diabetes mellitus. [NIH] Insulin-dependent diabetes mellitus: A disease characterized by high levels of blood glucose resulting from defects in insulin secretion, insulin action, or both. Autoimmune, genetic, and environmental factors are involved in the development of type I diabetes. [NIH] Interferon: A biological response modifier (a substance that can improve the body's natural

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response to disease). Interferons interfere with the division of cancer cells and can slow tumor growth. There are several types of interferons, including interferon-alpha, -beta, and gamma. These substances are normally produced by the body. They are also made in the laboratory for use in treating cancer and other diseases. [NIH] Interferon-alpha: One of the type I interferons produced by peripheral blood leukocytes or lymphoblastoid cells when exposed to live or inactivated virus, double-stranded RNA, or bacterial products. It is the major interferon produced by virus-induced leukocyte cultures and, in addition to its pronounced antiviral activity, it causes activation of NK cells. [NIH] Interleukin-1: A soluble factor produced by monocytes, macrophages, and other cells which activates T-lymphocytes and potentiates their response to mitogens or antigens. IL-1 consists of two distinct forms, IL-1 alpha and IL-1 beta which perform the same functions but are distinct proteins. The biological effects of IL-1 include the ability to replace macrophage requirements for T-cell activation. The factor is distinct from interleukin-2. [NIH] Interleukin-12: A heterodimeric cytokine that stimulates the production of interferon gamma from T-cells and natural killer cells, and also induces differentiation of Th1 helper cells. It is an initiator of cell-mediated immunity. [NIH] Interleukin-2: Chemical mediator produced by activated T lymphocytes and which regulates the proliferation of T cells, as well as playing a role in the regulation of NK cell activity. [NIH] Intermittent: Occurring at separated intervals; having periods of cessation of activity. [EU] Interstitial: Pertaining to or situated between parts or in the interspaces of a tissue. [EU] Intervention Studies: Epidemiologic investigations designed to test a hypothesized causeeffect relation by modifying the supposed causal factor(s) in the study population. [NIH] Intestinal: Having to do with the intestines. [NIH] Intestinal Flora: The bacteria, yeasts, and fungi that grow normally in the intestines. [NIH] Intestine: A long, tube-shaped organ in the abdomen that completes the process of digestion. There is both a large intestine and a small intestine. Also called the bowel. [NIH] Intracellular: Inside a cell. [NIH] Intracellular Membranes: Membranes of subcellular structures. [NIH] Intracranial Hemorrhages: Bleeding within the intracranial cavity, including hemorrhages in the brain and within the cranial epidural, subdural, and subarachnoid spaces. [NIH] Intracranial Hypertension: Increased pressure within the cranial vault. This may result from several conditions, including hydrocephalus; brain edema; intracranial masses; severe systemic hypertension; pseudotumor cerebri; and other disorders. [NIH] Intravenous: IV. Into a vein. [NIH] Intrinsic: Situated entirely within or pertaining exclusively to a part. [EU] Introns: Non-coding, intervening sequences of DNA that are transcribed, but are removed from within the primary gene transcript and rapidly degraded during maturation of messenger RNA. Most genes in the nuclei of eukaryotes contain introns, as do mitochondrial and chloroplast genes. [NIH] Invasive: 1. Having the quality of invasiveness. 2. Involving puncture or incision of the skin or insertion of an instrument or foreign material into the body; said of diagnostic techniques. [EU]

Involuntary: Reaction occurring without intention or volition. [NIH] Iodine: A nonmetallic element of the halogen group that is represented by the atomic

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symbol I, atomic number 53, and atomic weight of 126.90. It is a nutritionally essential element, especially important in thyroid hormone synthesis. In solution, it has anti-infective properties and is used topically. [NIH] Ion Channels: Gated, ion-selective glycoproteins that traverse membranes. The stimulus for channel gating can be a membrane potential, drug, transmitter, cytoplasmic messenger, or a mechanical deformation. Ion channels which are integral parts of ionotropic neurotransmitter receptors are not included. [NIH] Ion Exchange: Reversible chemical reaction between a solid, often an ION exchange resin, and a fluid whereby ions may be exchanged from one substance to another. This technique is used in water purification, in research, and in industry. [NIH] Ionization: 1. Any process by which a neutral atom gains or loses electrons, thus acquiring a net charge, as the dissociation of a substance in solution into ions or ion production by the passage of radioactive particles. 2. Iontophoresis. [EU] Ionizing: Radiation comprising charged particles, e. g. electrons, protons, alpha-particles, etc., having sufficient kinetic energy to produce ionization by collision. [NIH] Ions: An atom or group of atoms that have a positive or negative electric charge due to a gain (negative charge) or loss (positive charge) of one or more electrons. Atoms with a positive charge are known as cations; those with a negative charge are anions. [NIH] Irrigation: The washing of a body cavity or surface by flowing solution which is inserted and then removed. Any drug in the irrigation solution may be absorbed. [NIH] Irritable Bowel Syndrome: A disorder that comes and goes. Nerves that control the muscles in the GI tract are too active. The GI tract becomes sensitive to food, stool, gas, and stress. Causes abdominal pain, bloating, and constipation or diarrhea. Also called spastic colon or mucous colitis. [NIH] Ischemia: Deficiency of blood in a part, due to functional constriction or actual obstruction of a blood vessel. [EU] Ischemic Colitis: Decreased blood flow to the colon. Causes fever, pain, and bloody diarrhea. [NIH] Isocitrate Dehydrogenase: An enzyme of the oxidoreductase class that catalyzes the conversion of isocitrate and NAD+ to yield 2-ketoglutarate, carbon dioxide, and NADH. It occurs in cell mitochondria. The enzyme requires Mg2+, Mn2+; it is activated by ADP, citrate, and Ca2+, and inhibited by NADH, NADPH, and ATP. The reaction is the key ratelimiting step of the citric acid (tricarboxylic) cycle. (From Dorland, 27th ed) (The NADP+ enzyme is EC 1.1.1.42.) EC 1.1.1.41. [NIH] Isoelectric: Separation of amphoteric substances, dissolved in water, based on their isoelectric behavior. The amphoteric substances are a mixture of proteins to be separated and of auxiliary "carrier ampholytes". [NIH] Isoelectric Point: The pH in solutions of proteins and related compounds at which the dipolar ions are at a maximum. [NIH] Joint: The point of contact between elements of an animal skeleton with the parts that surround and support it. [NIH] Kb: A measure of the length of DNA fragments, 1 Kb = 1000 base pairs. The largest DNA fragments are up to 50 kilobases long. [NIH] Keratin: A class of fibrous proteins or scleroproteins important both as structural proteins and as keys to the study of protein conformation. The family represents the principal constituent of epidermis, hair, nails, horny tissues, and the organic matrix of tooth enamel. Two major conformational groups have been characterized, alpha-keratin, whose peptide

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backbone forms an alpha-helix, and beta-keratin, whose backbone forms a zigzag or pleated sheet structure. [NIH] Keratinocytes: Epidermal cells which synthesize keratin and undergo characteristic changes as they move upward from the basal layers of the epidermis to the cornified (horny) layer of the skin. Successive stages of differentiation of the keratinocytes forming the epidermal layers are basal cell, spinous or prickle cell, and the granular cell. [NIH] Kidney Disease: Any one of several chronic conditions that are caused by damage to the cells of the kidney. People who have had diabetes for a long time may have kidney damage. Also called nephropathy. [NIH] Kidney Failure: The inability of a kidney to excrete metabolites at normal plasma levels under conditions of normal loading, or the inability to retain electrolytes under conditions of normal intake. In the acute form (kidney failure, acute), it is marked by uremia and usually by oliguria or anuria, with hyperkalemia and pulmonary edema. The chronic form (kidney failure, chronic) is irreversible and requires hemodialysis. [NIH] Kidney Failure, Acute: A clinical syndrome characterized by a sudden decrease in glomerular filtration rate, often to values of less than 1 to 2 ml per minute. It is usually associated with oliguria (urine volumes of less than 400 ml per day) and is always associated with biochemical consequences of the reduction in glomerular filtration rate such as a rise in blood urea nitrogen (BUN) and serum creatinine concentrations. [NIH] Kidney Failure, Chronic: An irreversible and usually progressive reduction in renal function in which both kidneys have been damaged by a variety of diseases to the extent that they are unable to adequately remove the metabolic products from the blood and regulate the body's electrolyte composition and acid-base balance. Chronic kidney failure requires hemodialysis or surgery, usually kidney transplantation. [NIH] Kinetic: Pertaining to or producing motion. [EU] Kluyveromyces: An ascomycetous yeast of the fungal family Saccharomycetaceae, order Saccharomycetales. [NIH] Labile: 1. Gliding; moving from point to point over the surface; unstable; fluctuating. 2. Chemically unstable. [EU] Lactation: The period of the secretion of milk. [EU] Lactobacillus: A genus of gram-positive, microaerophilic, rod-shaped bacteria occurring widely in nature. Its species are also part of the many normal flora of the mouth, intestinal tract, and vagina of many mammals, including humans. Pathogenicity from this genus is rare. [NIH] Lactobacillus acidophilus: A species of gram-positive, rod-shaped bacteria isolated from the intestinal tract of humans and animals, the human mouth, and vagina. This organism produces the fermented product, acidophilus milk. [NIH] Lactobacillus casei: A rod-shaped bacterium isolated from milk and cheese, dairy products and dairy environments, sour dough, cow dung, silage, and human mouth, human intestinal contents and stools, and the human vagina. [NIH] Large Intestine: The part of the intestine that goes from the cecum to the rectum. The large intestine absorbs water from stool and changes it from a liquid to a solid form. The large intestine is 5 feet long and includes the appendix, cecum, colon, and rectum. Also called colon. [NIH] Latent: Phoria which occurs at one distance or another and which usually has no troublesome effect. [NIH] Laxative: An agent that acts to promote evacuation of the bowel; a cathartic or purgative.

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[EU]

Lectin: A complex molecule that has both protein and sugars. Lectins are able to bind to the outside of a cell and cause biochemical changes in it. Lectins are made by both animals and plants. [NIH] Lens: The transparent, double convex (outward curve on both sides) structure suspended between the aqueous and vitreous; helps to focus light on the retina. [NIH] Leprosy: A chronic granulomatous infection caused by Mycobacterium leprae. The granulomatous lesions are manifested in the skin, the mucous membranes, and the peripheral nerves. Two polar or principal types are lepromatous and tuberculoid. [NIH] Lesion: An area of abnormal tissue change. [NIH] Lethal: Deadly, fatal. [EU] Lethargy: Abnormal drowsiness or stupor; a condition of indifference. [EU] Leucine: An essential branched-chain amino acid important for hemoglobin formation. [NIH] Leuconostoc: A genus of gram-positive, facultatively anaerobic bacteria whose growth is dependent on the presence of a fermentable carbohydrate. It is nonpathogenic to plants and animals, including humans. [NIH] Leukemia: Cancer of blood-forming tissue. [NIH] Leukocytes: White blood cells. These include granular leukocytes (basophils, eosinophils, and neutrophils) as well as non-granular leukocytes (lymphocytes and monocytes). [NIH] Leukotrienes: A family of biologically active compounds derived from arachidonic acid by oxidative metabolism through the 5-lipoxygenase pathway. They participate in host defense reactions and pathophysiological conditions such as immediate hypersensitivity and inflammation. They have potent actions on many essential organs and systems, including the cardiovascular, pulmonary, and central nervous system as well as the gastrointestinal tract and the immune system. [NIH] Library Services: Services offered to the library user. They include reference and circulation. [NIH]

Life cycle: The successive stages through which an organism passes from fertilized ovum or spore to the fertilized ovum or spore of the next generation. [NIH] Ligament: A band of fibrous tissue that connects bones or cartilages, serving to support and strengthen joints. [EU] Ligands: A RNA simulation method developed by the MIT. [NIH] Ligase: An enzyme that repairs single stranded discontinuities in double-stranded DNA molecules in the cell. Purified DNA ligase is used in gene cloning to join DNA molecules together. [NIH] Ligation: Application of a ligature to tie a vessel or strangulate a part. [NIH] Linkage: The tendency of two or more genes in the same chromosome to remain together from one generation to the next more frequently than expected according to the law of independent assortment. [NIH] Lipid: Fat. [NIH] Lipid Peroxidation: Peroxidase catalyzed oxidation of lipids using hydrogen peroxide as an electron acceptor. [NIH] Lipopolysaccharide: Substance consisting of polysaccaride and lipid. [NIH] Lipoprotein: Any of the lipid-protein complexes in which lipids are transported in the blood; lipoprotein particles consist of a spherical hydrophobic core of triglycerides or

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cholesterol esters surrounded by an amphipathic monolayer of phospholipids, cholesterol, and apolipoproteins; the four principal classes are high-density, low-density, and very-lowdensity lipoproteins and chylomicrons. [EU] Liposome: A spherical particle in an aqueous medium, formed by a lipid bilayer enclosing an aqueous compartment. [EU] Lipoxygenase: An enzyme of the oxidoreductase class that catalyzes reactions between linoleate and other fatty acids and oxygen to form hydroperoxy-fatty acid derivatives. Related enzymes in this class include the arachidonate lipoxygenases, arachidonate 5lipoxygenase, arachidonate 12-lipoxygenase, and arachidonate 15-lipoxygenase. EC 1.13.11.12. [NIH] Lisofylline: A drug that may protect healthy cells from chemotherapy and radiation without inhibiting the effects of these therapies on tumor cells. [NIH] Listeria monocytogenes: A species of gram-positive, rod-shaped bacteria widely distributed in nature. It has been isolated from sewage, soil, silage, and from feces of healthy animals and man. Infection with this bacterium leads to encephalitis, meningitis, endocarditis, and abortion. [NIH] Liver: A large, glandular organ located in the upper abdomen. The liver cleanses the blood and aids in digestion by secreting bile. [NIH] Liver Neoplasms: Tumors or cancer of the liver. [NIH] Lobe: A portion of an organ such as the liver, lung, breast, or brain. [NIH] Localization: The process of determining or marking the location or site of a lesion or disease. May also refer to the process of keeping a lesion or disease in a specific location or site. [NIH] Localized: Cancer which has not metastasized yet. [NIH] Locomotion: Movement or the ability to move from one place or another. It can refer to humans, vertebrate or invertebrate animals, and microorganisms. [NIH] Loop: A wire usually of platinum bent at one end into a small loop (usually 4 mm inside diameter) and used in transferring microorganisms. [NIH] Lorazepam: An anti-anxiety agent with few side effects. It also has hypnotic, anticonvulsant, and considerable sedative properties and has been proposed as a preanesthetic agent. [NIH] Low-density lipoprotein: Lipoprotein that contains most of the cholesterol in the blood. LDL carries cholesterol to the tissues of the body, including the arteries. A high level of LDL increases the risk of heart disease. LDL typically contains 60 to 70 percent of the total serum cholesterol and both are directly correlated with CHD risk. [NIH] Luciferase: Any one of several enzymes that catalyze the bioluminescent reaction in certain marine crustaceans, fish, bacteria, and insects. The enzyme is a flavoprotein; it oxidizes luciferins to an electronically excited compound that emits energy in the form of light. The color of light emitted varies with the organism. The firefly enzyme is a valuable reagent for measurement of ATP concentration. (Dorland, 27th ed) EC 1.13.12.-. [NIH] Lumen: The cavity or channel within a tube or tubular organ. [EU] Lymph: The almost colorless fluid that travels through the lymphatic system and carries cells that help fight infection and disease. [NIH] Lymph node: A rounded mass of lymphatic tissue that is surrounded by a capsule of connective tissue. Also known as a lymph gland. Lymph nodes are spread out along lymphatic vessels and contain many lymphocytes, which filter the lymphatic fluid (lymph). [NIH]

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Lymphangitis: Inflammation of a lymphatic vessel or vessels. Acute lymphangitis may result from spread of bacterial infection (most commonly beta-haemolytic streptococci) into the lymphatics, manifested by painful subcutaneous red streaks along the course of the vessels. [EU] Lymphatic: The tissues and organs, including the bone marrow, spleen, thymus, and lymph nodes, that produce and store cells that fight infection and disease. [NIH] Lymphatic system: The tissues and organs that produce, store, and carry white blood cells that fight infection and other diseases. This system includes the bone marrow, spleen, thymus, lymph nodes and a network of thin tubes that carry lymph and white blood cells. These tubes branch, like blood vessels, into all the tissues of the body. [NIH] Lymphoblastic: One of the most aggressive types of non-Hodgkin lymphoma. [NIH] Lymphoblasts: Interferon produced predominantly by leucocyte cells. [NIH] Lymphocyte: A white blood cell. Lymphocytes have a number of roles in the immune system, including the production of antibodies and other substances that fight infection and diseases. [NIH] Lymphocyte Count: A count of the number of lymphocytes in the blood. [NIH] Lymphoid: Referring to lymphocytes, a type of white blood cell. Also refers to tissue in which lymphocytes develop. [NIH] Lymphoma: A general term for various neoplastic diseases of the lymphoid tissue. [NIH] Lysine: An essential amino acid. It is often added to animal feed. [NIH] Lysophospholipase: An enzyme that catalyzes the hydrolysis of a single fatty acid ester bond in lysoglycerophosphatidates with the formation of glyceryl phosphatidates and a fatty acid. EC 3.1.1.5. [NIH] Lysosome: A sac-like compartment inside a cell that has enzymes that can break down cellular components that need to be destroyed. [NIH] Lytic: 1. Pertaining to lysis or to a lysin. 2. Producing lysis. [EU] Macrolides: A group of organic compounds that contain a macrocyclic lactone ring linked glycosidically to one or more sugar moieties. [NIH] Macrophage: A type of white blood cell that surrounds and kills microorganisms, removes dead cells, and stimulates the action of other immune system cells. [NIH] Major Histocompatibility Complex: The genetic region which contains the loci of genes which determine the structure of the serologically defined (SD) and lymphocyte-defined (LD) transplantation antigens, genes which control the structure of the immune responseassociated (Ia) antigens, the immune response (Ir) genes which control the ability of an animal to respond immunologically to antigenic stimuli, and genes which determine the structure and/or level of the first four components of complement. [NIH] Malabsorption: Impaired intestinal absorption of nutrients. [EU] Malaria: A protozoan disease caused in humans by four species of the genus Plasmodium (P. falciparum (malaria, falciparum), P. vivax (malaria, vivax), P. ovale, and P. malariae) and transmitted by the bite of an infected female mosquito of the genus Anopheles. Malaria is endemic in parts of Asia, Africa, Central and South America, Oceania, and certain Caribbean islands. It is characterized by extreme exhaustion associated with paroxysms of high fever, sweating, shaking chills, and anemia. Malaria in animals is caused by other species of plasmodia. [NIH] Malaria, Falciparum: Malaria caused by Plasmodium falciparum. This is the severest form of malaria and is associated with the highest levels of parasites in the blood. This disease is

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characterized by irregularly recurring febrile paroxysms that in extreme cases occur with acute cerebral, renal, or gastrointestinal manifestations. [NIH] Malaria, Vivax: Malaria caused by Plasmodium vivax. This form of malaria is less severe than malaria, falciparum, but there is a higher probability for relapses to occur. Febrile paroxysms often occur every other day. [NIH] Malate Dehydrogenase: An enzyme that catalyzes the conversion of (S)-malate and NAD+ to oxaloacetate and NADH. EC 1.1.1.37. [NIH] Malignant: Cancerous; a growth with a tendency to invade and destroy nearby tissue and spread to other parts of the body. [NIH] Malnutrition: A condition caused by not eating enough food or not eating a balanced diet. [NIH]

Mammary: Pertaining to the mamma, or breast. [EU] Mastitis: Inflammatory disease of the breast, or mammary gland. [NIH] Mastoiditis: Inflammation of the cavity and air cells in the mastoid part of the temporal bone. [NIH] Matrix metalloproteinase: A member of a group of enzymes that can break down proteins, such as collagen, that are normally found in the spaces between cells in tissues (i.e., extracellular matrix proteins). Because these enzymes need zinc or calcium atoms to work properly, they are called metalloproteinases. Matrix metalloproteinases are involved in wound healing, angiogenesis, and tumor cell metastasis. [NIH] Meat: The edible portions of any animal used for food including domestic mammals (the major ones being cattle, swine, and sheep) along with poultry, fish, shellfish, and game. [NIH]

Meconium: The thick green-to-black mucilaginous material found in the intestines of a fullterm fetus. It consists of secretions of the intestinal glands, bile pigments, fatty acids, amniotic fluid, and intrauterine debris. It constitutes the first stools passed by a newborn. [NIH]

Mediate: Indirect; accomplished by the aid of an intervening medium. [EU] Mediator: An object or substance by which something is mediated, such as (1) a structure of the nervous system that transmits impulses eliciting a specific response; (2) a chemical substance (transmitter substance) that induces activity in an excitable tissue, such as nerve or muscle; or (3) a substance released from cells as the result of the interaction of antigen with antibody or by the action of antigen with a sensitized lymphocyte. [EU] MEDLINE: An online database of MEDLARS, the computerized bibliographic Medical Literature Analysis and Retrieval System of the National Library of Medicine. [NIH] Megakaryocytes: Very large bone marrow cells which release mature blood platelets. [NIH] Meiosis: A special method of cell division, occurring in maturation of the germ cells, by means of which each daughter nucleus receives half the number of chromosomes characteristic of the somatic cells of the species. [NIH] Melanin: The substance that gives the skin its color. [NIH] Melanocytes: Epidermal dendritic pigment cells which control long-term morphological color changes by alteration in their number or in the amount of pigment they produce and store in the pigment containing organelles called melanosomes. Melanophores are larger cells which do not exist in mammals. [NIH] Melanoma: A form of skin cancer that arises in melanocytes, the cells that produce pigment. Melanoma usually begins in a mole. [NIH]

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Membrane: A very thin layer of tissue that covers a surface. [NIH] Membrane Proteins: Proteins which are found in membranes including cellular and intracellular membranes. They consist of two types, peripheral and integral proteins. They include most membrane-associated enzymes, antigenic proteins, transport proteins, and drug, hormone, and lectin receptors. [NIH] Meninges: The three membranes that cover and protect the brain and spinal cord. [NIH] Meningitis: Inflammation of the meninges. When it affects the dura mater, the disease is termed pachymeningitis; when the arachnoid and pia mater are involved, it is called leptomeningitis, or meningitis proper. [EU] Menopause: Permanent cessation of menstruation. [NIH] Mental Disorders: Psychiatric illness or diseases manifested by breakdowns in the adaptational process expressed primarily as abnormalities of thought, feeling, and behavior producing either distress or impairment of function. [NIH] Mental Health: The state wherein the person is well adjusted. [NIH] Mental Processes: Conceptual functions or thinking in all its forms. [NIH] Mental Retardation: Refers to sub-average general intellectual functioning which originated during the developmental period and is associated with impairment in adaptive behavior. [NIH]

Mesenchymal: Refers to cells that develop into connective tissue, blood vessels, and lymphatic tissue. [NIH] Mesenteric: Pertaining to the mesentery : a membranous fold attaching various organs to the body wall. [EU] Mesenteric Lymphadenitis: Inflammation of the mesenteric lymph nodes. [NIH] Mesentery: A layer of the peritoneum which attaches the abdominal viscera to the abdominal wall and conveys their blood vessels and nerves. [NIH] Mesocolon: The fold of peritoneum by which the colon is attached to the posterior abdominal wall. [NIH] Mesoderm: The middle germ layer of the embryo. [NIH] Meta-Analysis: A quantitative method of combining the results of independent studies (usually drawn from the published literature) and synthesizing summaries and conclusions which may be used to evaluate therapeutic effectiveness, plan new studies, etc., with application chiefly in the areas of research and medicine. [NIH] Metabolite: Any substance produced by metabolism or by a metabolic process. [EU] Metaphase: The second phase of cell division, in which the chromosomes line up across the equatorial plane of the spindle prior to separation. [NIH] Metastasis: The spread of cancer from one part of the body to another. Tumors formed from cells that have spread are called "secondary tumors" and contain cells that are like those in the original (primary) tumor. The plural is metastases. [NIH] Methionine: A sulfur containing essential amino acid that is important in many body functions. It is a chelating agent for heavy metals. [NIH] Methyltransferase: A drug-metabolizing enzyme. [NIH] MI: Myocardial infarction. Gross necrosis of the myocardium as a result of interruption of the blood supply to the area; it is almost always caused by atherosclerosis of the coronary arteries, upon which coronary thrombosis is usually superimposed. [NIH] Microbe: An organism which cannot be observed with the naked eye; e. g. unicellular

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animals, lower algae, lower fungi, bacteria. [NIH] Microbiological: Pertaining to microbiology : the science that deals with microorganisms, including algae, bacteria, fungi, protozoa and viruses. [EU] Microbiology: The study of microorganisms such as fungi, bacteria, algae, archaea, and viruses. [NIH] Microorganism: An organism that can be seen only through a microscope. Microorganisms include bacteria, protozoa, algae, and fungi. Although viruses are not considered living organisms, they are sometimes classified as microorganisms. [NIH] Micro-organism: An organism which cannot be observed with the naked eye; e. g. unicellular animals, lower algae, lower fungi, bacteria. [NIH] Microscopy: The application of microscope magnification to the study of materials that cannot be properly seen by the unaided eye. [NIH] Microspheres: Small uniformly-sized spherical particles frequently radioisotopes or various reagents acting as tags or markers. [NIH]

labeled

with

Microtubules: Slender, cylindrical filaments found in the cytoskeleton of plant and animal cells. They are composed of the protein tubulin. [NIH] Microvilli: Minute projections of cell membranes which greatly increase the surface area of the cell. [NIH] Migrans: Infestation of the dermis by various larvae, characterized by bizarre red irregular lines which are broad at one end and fade at the other, produced by burrowing larvae. [NIH] Milligram: A measure of weight. A milligram is approximately 450,000-times smaller than a pound and 28,000-times smaller than an ounce. [NIH] Mistletoe lectin: A substance that comes from the mistletoe plant, and that is being studied as a treatment for cancer. A lectin is a complex molecule that has both protein and sugars. Lectins are able to bind to the outside of a cell and cause biochemical changes in it. Lectins are made by both animals and plants. [NIH] Mitochondria: Parts of a cell where aerobic production (also known as cell respiration) takes place. [NIH] Mitochondrial Swelling: Increase in volume of mitochondria due to an influx of fluid; it occurs in hypotonic solutions due to osmotic pressure and in isotonic solutions as a result of altered permeability of the membranes of respiring mitochondria. [NIH] Mitosis: A method of indirect cell division by means of which the two daughter nuclei normally receive identical complements of the number of chromosomes of the somatic cells of the species. [NIH] Mitotic: Cell resulting from mitosis. [NIH] Mobility: Capability of movement, of being moved, or of flowing freely. [EU] Modeling: A treatment procedure whereby the therapist presents the target behavior which the learner is to imitate and make part of his repertoire. [NIH] Modification: A change in an organism, or in a process in an organism, that is acquired from its own activity or environment. [NIH] Modulator: A specific inductor that brings out characteristics peculiar to a definite region. [EU]

Molecular: Of, pertaining to, or composed of molecules : a very small mass of matter. [EU] Molecular mass: The sum of the atomic masses of all atoms in a molecule, based on a scale in which the atomic masses of hydrogen, carbon, nitrogen, and oxygen are 1, 12, 14, and 16,

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respectively. For example, the molecular mass of water, which has two atoms of hydrogen and one atom of oxygen, is 18 (i.e., 2 + 16). [NIH] Molecular Structure: The location of the atoms, groups or ions relative to one another in a molecule, as well as the number, type and location of covalent bonds. [NIH] Molecule: A chemical made up of two or more atoms. The atoms in a molecule can be the same (an oxygen molecule has two oxygen atoms) or different (a water molecule has two hydrogen atoms and one oxygen atom). Biological molecules, such as proteins and DNA, can be made up of many thousands of atoms. [NIH] Monitor: An apparatus which automatically records such physiological signs as respiration, pulse, and blood pressure in an anesthetized patient or one undergoing surgical or other procedures. [NIH] Monoclonal: An antibody produced by culturing a single type of cell. It therefore consists of a single species of immunoglobulin molecules. [NIH] Monoclonal antibodies: Laboratory-produced substances that can locate and bind to cancer cells wherever they are in the body. Many monoclonal antibodies are used in cancer detection or therapy; each one recognizes a different protein on certain cancer cells. Monoclonal antibodies can be used alone, or they can be used to deliver drugs, toxins, or radioactive material directly to a tumor. [NIH] Monocytes: Large, phagocytic mononuclear leukocytes produced in the vertebrate bone marrow and released into the blood; contain a large, oval or somewhat indented nucleus surrounded by voluminous cytoplasm and numerous organelles. [NIH] Mononuclear: A cell with one nucleus. [NIH] Morphological: Relating to the configuration or the structure of live organs. [NIH] Morphology: The science of the form and structure of organisms (plants, animals, and other forms of life). [NIH] Motion Sickness: Sickness caused by motion, as sea sickness, train sickness, car sickness, and air sickness. [NIH] Motor Activity: The physical activity of an organism as a behavioral phenomenon. [NIH] Mucilaginous: Pertaining to or secreting mucus. [NIH] Mucins: A secretion containing mucopolysaccharides and protein that is the chief constituent of mucus. [NIH] Mucosa: A mucous membrane, or tunica mucosa. [EU] Mucosal Ulceration: Skin ulceration in workers who work with lime and lime solutions. [NIH]

Mucus: The viscous secretion of mucous membranes. It contains mucin, white blood cells, water, inorganic salts, and exfoliated cells. [NIH] Multidrug resistance: Adaptation of tumor cells to anticancer drugs in ways that make the drugs less effective. [NIH] Multiple Organ Failure: A progressive condition usually characterized by combined failure of several organs such as the lungs, liver, kidney, along with some clotting mechanisms, usually postinjury or postoperative. [NIH] Multiple sclerosis: A disorder of the central nervous system marked by weakness, numbness, a loss of muscle coordination, and problems with vision, speech, and bladder control. Multiple sclerosis is thought to be an autoimmune disease in which the body's immune system destroys myelin. Myelin is a substance that contains both protein and fat (lipid) and serves as a nerve insulator and helps in the transmission of nerve signals. [NIH]

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Multivalent: Pertaining to a group of 5 or more homologous or partly homologous chromosomes during the zygotene stage of prophase to first metaphasis in meiosis. [NIH] Muscle Fibers: Large single cells, either cylindrical or prismatic in shape, that form the basic unit of muscle tissue. They consist of a soft contractile substance enclosed in a tubular sheath. [NIH] Muscular Atrophy: Derangement in size and number of muscle fibers occurring with aging, reduction in blood supply, or following immobilization, prolonged weightlessness, malnutrition, and particularly in denervation. [NIH] Muscular Dystrophies: A general term for a group of inherited disorders which are characterized by progressive degeneration of skeletal muscles. [NIH] Mustard Gas: Severe irritant and vesicant of skin, eyes, and lungs. It may cause blindness and lethal lung edema and was formerly used as a war gas. The substance has been proposed as a cytostatic and for treatment of psoriasis. It has been listed as a known carcinogen in the Fourth Annual Report on Carcinogens (NTP-85-002, 1985) (Merck, 11th ed). [NIH] Mutagen: Any agent, such as X-rays, gamma rays, mustard gas, TCDD, that can cause abnormal mutation in living cells; having the power to cause mutations. [NIH] Mutagenesis: Process of generating genetic mutations. It may occur spontaneously or be induced by mutagens. [NIH] Mutagenic: Inducing genetic mutation. [EU] Mutagenicity: Ability to damage DNA, the genetic material; the power to cause mutations. [NIH]

Mycobacterial disease: Any disease caused by Mycobacterium other than M. tuberculosis, M. bovis, and M. avium. [NIH] Mycobacterium: A genus of gram-positive, aerobic bacteria. Most species are free-living in soil and water, but the major habitat for some is the diseased tissue of warm-blooded hosts. [NIH]

Myelin: The fatty substance that covers and protects nerves. [NIH] Myocardium: The muscle tissue of the heart composed of striated, involuntary muscle known as cardiac muscle. [NIH] Myoglobin: A conjugated protein which is the oxygen-transporting pigment of muscle. It is made up of one globin polypeptide chain and one heme group. [NIH] Myotonic Dystrophy: A condition presenting muscle weakness and wasting which may be progressive. [NIH] Nalidixic Acid: Synthetic antimicrobial agent used in urinary tract infections. It is active against gram-negative bacteria but has little activity against gram-positive organisms or Pseudomonas. [NIH] Natural killer cells: NK cells. A type of white blood cell that contains granules with enzymes that can kill tumor cells or microbial cells. Also called large granular lymphocytes (LGL). [NIH] Natural selection: A part of the evolutionary process resulting in the survival and reproduction of the best adapted individuals. [NIH] Nausea: An unpleasant sensation in the stomach usually accompanied by the urge to vomit. Common causes are early pregnancy, sea and motion sickness, emotional stress, intense pain, food poisoning, and various enteroviruses. [NIH] NCI: National Cancer Institute. NCI, part of the National Institutes of Health of the United

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States Department of Health and Human Services, is the federal government's principal agency for cancer research. NCI conducts, coordinates, and funds cancer research, training, health information dissemination, and other programs with respect to the cause, diagnosis, prevention, and treatment of cancer. Access the NCI Web site at http://cancer.gov. [NIH] Necrosis: A pathological process caused by the progressive degradative action of enzymes that is generally associated with severe cellular trauma. It is characterized by mitochondrial swelling, nuclear flocculation, uncontrolled cell lysis, and ultimately cell death. [NIH] Need: A state of tension or dissatisfaction felt by an individual that impels him to action toward a goal he believes will satisfy the impulse. [NIH] Neonatal: Pertaining to the first four weeks after birth. [EU] Neonatal period: The first 4 weeks after birth. [NIH] Neoplasia: Abnormal and uncontrolled cell growth. [NIH] Neoplasm: A new growth of benign or malignant tissue. [NIH] Neoplastic: Pertaining to or like a neoplasm (= any new and abnormal growth); pertaining to neoplasia (= the formation of a neoplasm). [EU] Nephropathy: Disease of the kidneys. [EU] Nerve: A cordlike structure of nervous tissue that connects parts of the nervous system with other tissues of the body and conveys nervous impulses to, or away from, these tissues. [NIH] Nervous System: The entire nerve apparatus composed of the brain, spinal cord, nerves and ganglia. [NIH] Networks: Pertaining to a nerve or to the nerves, a meshlike structure of interlocking fibers or strands. [NIH] Neural: 1. Pertaining to a nerve or to the nerves. 2. Situated in the region of the spinal axis, as the neutral arch. [EU] Neuroendocrine: Having to do with the interactions between the nervous system and the endocrine system. Describes certain cells that release hormones into the blood in response to stimulation of the nervous system. [NIH] Neurologic: Having to do with nerves or the nervous system. [NIH] Neuronal: Pertaining to a neuron or neurons (= conducting cells of the nervous system). [EU] Neurons: The basic cellular units of nervous tissue. Each neuron consists of a body, an axon, and dendrites. Their purpose is to receive, conduct, and transmit impulses in the nervous system. [NIH] Neuropeptide: A member of a class of protein-like molecules made in the brain. Neuropeptides consist of short chains of amino acids, with some functioning as neurotransmitters and some functioning as hormones. [NIH] Neurotoxic: Poisonous or destructive to nerve tissue. [EU] Neurotoxins: Toxic substances from microorganisms, plants or animals that interfere with the functions of the nervous system. Most venoms contain neurotoxic substances. Myotoxins are included in this concept. [NIH] Neurotransmitters: Endogenous signaling molecules that alter the behavior of neurons or effector cells. Neurotransmitter is used here in its most general sense, including not only messengers that act directly to regulate ion channels, but also those that act through second messenger systems, and those that act at a distance from their site of release. Included are neuromodulators, neuroregulators, neuromediators, and neurohumors, whether or not acting at synapses. [NIH]

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Neutrons: Electrically neutral elementary particles found in all atomic nuclei except light hydrogen; the mass is equal to that of the proton and electron combined and they are unstable when isolated from the nucleus, undergoing beta decay. Slow, thermal, epithermal, and fast neutrons refer to the energy levels with which the neutrons are ejected from heavier nuclei during their decay. [NIH] Neutrophil: A type of white blood cell. [NIH] Neutrophil Infiltration: The diffusion or accumulation of neutrophils in tissues or cells in response to a wide variety of substances released at the sites of inflammatory reactions. [NIH] Nitric Oxide: A free radical gas produced endogenously by a variety of mammalian cells. It is synthesized from arginine by a complex reaction, catalyzed by nitric oxide synthase. Nitric oxide is endothelium-derived relaxing factor. It is released by the vascular endothelium and mediates the relaxation induced by some vasodilators such as acetylcholine and bradykinin. It also inhibits platelet aggregation, induces disaggregation of aggregated platelets, and inhibits platelet adhesion to the vascular endothelium. Nitric oxide activates cytosolic guanylate cyclase and thus elevates intracellular levels of cyclic GMP. [NIH]

Nitrofurantoin: A urinary anti-infective agent effective against most gram-positive and gram-negative organisms. Although sulfonamides and antibiotics are usually the agents of choice for urinary tract infections, nitrofurantoin is widely used for prophylaxis and longterm suppression. [NIH] Nitrogen: An element with the atomic symbol N, atomic number 7, and atomic weight 14. Nitrogen exists as a diatomic gas and makes up about 78% of the earth's atmosphere by volume. It is a constituent of proteins and nucleic acids and found in all living cells. [NIH] Norepinephrine: Precursor of epinephrine that is secreted by the adrenal medulla and is a widespread central and autonomic neurotransmitter. Norepinephrine is the principal transmitter of most postganglionic sympathetic fibers and of the diffuse projection system in the brain arising from the locus ceruleus. It is also found in plants and is used pharmacologically as a sympathomimetic. [NIH] Norfloxacin: Quinoline-derived synthetic antibacterial agent with a very broad spectrum of action. Oral administration yields highly bactericidal plasma, tissue, and urine levels. Norfloxacin inhibits bacterial DNA-gyrase and is used in gastrointestinal, eye, and urinary infections. [NIH] Nosocomial: Pertaining to or originating in the hospital, said of an infection not present or incubating prior to admittance to the hospital, but generally occurring 72 hours after admittance; the term is usually used to refer to patient disease, but hospital personnel may also acquire nosocomial infection. [EU] Nuclear: A test of the structure, blood flow, and function of the kidneys. The doctor injects a mildly radioactive solution into an arm vein and uses x-rays to monitor its progress through the kidneys. [NIH] Nuclei: A body of specialized protoplasm found in nearly all cells and containing the chromosomes. [NIH] Nucleic acid: Either of two types of macromolecule (DNA or RNA) formed by polymerization of nucleotides. Nucleic acids are found in all living cells and contain the information (genetic code) for the transfer of genetic information from one generation to the next. [NIH] Nucleic Acid Hybridization: The process whereby two single-stranded polynucleotides form a double-stranded molecule, with hydrogen bonding between the complementary bases in the two strains. [NIH]

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Nucleocapsid: A protein-nucleic acid complex which forms part or all of a virion. It consists of a capsid plus enclosed nucleic acid. Depending on the virus, the nucleocapsid may correspond to a naked core or be surrounded by a membranous envelope. [NIH] Nucleolus: A small dense body (sub organelle) within the nucleus of eukaryotic cells, visible by phase contrast and interference microscopy in live cells throughout interphase. Contains RNA and protein and is the site of synthesis of ribosomal RNA. [NIH] Nucleotidases: A class of enzymes that catalyze the conversion of a nucleotide and water to a nucleoside and orthophosphate. EC 3.1.3.-. [NIH] Nucleus: A body of specialized protoplasm found in nearly all cells and containing the chromosomes. [NIH] Nurseries: Facilities which provide care for infants. [NIH] Occult: Obscure; concealed from observation, difficult to understand. [EU] Odour: A volatile emanation that is perceived by the sense of smell. [EU] Oedema: The presence of abnormally large amounts of fluid in the intercellular tissue spaces of the body; usually applied to demonstrable accumulation of excessive fluid in the subcutaneous tissues. Edema may be localized, due to venous or lymphatic obstruction or to increased vascular permeability, or it may be systemic due to heart failure or renal disease. Collections of edema fluid are designated according to the site, e.g. ascites (peritoneal cavity), hydrothorax (pleural cavity), and hydropericardium (pericardial sac). Massive generalized edema is called anasarca. [EU] Oligosaccharides: Carbohydrates consisting of between two and ten monosaccharides connected by either an alpha- or beta-glycosidic link. They are found throughout nature in both the free and bound form. [NIH] Oliguria: Clinical manifestation of the urinary system consisting of a decrease in the amount of urine secreted. [NIH] Oncogene: A gene that normally directs cell growth. If altered, an oncogene can promote or allow the uncontrolled growth of cancer. Alterations can be inherited or caused by an environmental exposure to carcinogens. [NIH] On-line: A sexually-reproducing population derived from a common parentage. [NIH] Oocytes: Female germ cells in stages between the prophase of the first maturation division and the completion of the second maturation division. [NIH] Opacity: Degree of density (area most dense taken for reading). [NIH] Open Reading Frames: Reading frames where successive nucleotide triplets can be read as codons specifying amino acids and where the sequence of these triplets is not interrupted by stop codons. [NIH] Operon: The genetic unit consisting of a feedback system under the control of an operator gene, in which a structural gene transcribes its message in the form of mRNA upon blockade of a repressor produced by a regulator gene. Included here is the attenuator site of bacterial operons where transcription termination is regulated. [NIH] Opportunistic Infections: An infection caused by an organism which becomes pathogenic under certain conditions, e.g., during immunosuppression. [NIH] Opsin: A protein formed, together with retinene, by the chemical breakdown of metarhodopsin. [NIH] Orderly: A male hospital attendant. [NIH] Organ Culture: The growth in aseptic culture of plant organs such as roots or shoots, beginning with organ primordia or segments and maintaining the characteristics of the

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organ. [NIH] Organelles: Specific particles of membrane-bound organized living substances present in eukaryotic cells, such as the mitochondria; the golgi apparatus; endoplasmic reticulum; lysomomes; plastids; and vacuoles. [NIH] Osmolality: The concentration of osmotically active particles in solution expressed in terms of osmoles of solute per kilogram of solvent. The osmolality is directly proportional to the colligative properties of solutions; osmotic pressure, boiling point elevation, freezing point depression, and vapour pressure lowering. [EU] Osmoles: The standard unit of osmotic pressure. [NIH] Osmosis: Tendency of fluids (e.g., water) to move from the less concentrated to the more concentrated side of a semipermeable membrane. [NIH] Osmotic: Pertaining to or of the nature of osmosis (= the passage of pure solvent from a solution of lesser to one of greater solute concentration when the two solutions are separated by a membrane which selectively prevents the passage of solute molecules, but is permeable to the solvent). [EU] Otitis: Inflammation of the ear, which may be marked by pain, fever, abnormalities of hearing, hearing loss, tinnitus, and vertigo. [EU] Otitis Media: Inflammation of the middle ear. [NIH] Ovaries: The pair of female reproductive glands in which the ova, or eggs, are formed. The ovaries are located in the pelvis, one on each side of the uterus. [NIH] Overexpress: An excess of a particular protein on the surface of a cell. [NIH] Oxaloacetate: An anionic form of oxaloacetic acid. [NIH] Oxazepam: A benzodiazepine used in the treatment of anxiety, alcohol withdrawal, and insomnia. [NIH] Oxidants: Oxidizing agents or electron-accepting molecules in chemical reactions in which electrons are transferred from one molecule to another (oxidation-reduction). In vivo, it appears that phagocyte-generated oxidants function as tumor promoters or cocarcinogens rather than as complete carcinogens perhaps because of the high levels of endogenous antioxidant defenses. It is also thought that oxidative damage in joints may trigger the autoimmune response that characterizes the persistence of the rheumatoid disease process. [NIH]

Oxidation: The act of oxidizing or state of being oxidized. Chemically it consists in the increase of positive charges on an atom or the loss of negative charges. Most biological oxidations are accomplished by the removal of a pair of hydrogen atoms (dehydrogenation) from a molecule. Such oxidations must be accompanied by reduction of an acceptor molecule. Univalent o. indicates loss of one electron; divalent o., the loss of two electrons. [EU]

Oxidation-Reduction: A chemical reaction in which an electron is transferred from one molecule to another. The electron-donating molecule is the reducing agent or reductant; the electron-accepting molecule is the oxidizing agent or oxidant. Reducing and oxidizing agents function as conjugate reductant-oxidant pairs or redox pairs (Lehninger, Principles of Biochemistry, 1982, p471). [NIH] Oxidative metabolism: A chemical process in which oxygen is used to make energy from carbohydrates (sugars). Also known as aerobic respiration, cell respiration, or aerobic metabolism. [NIH] Oxidative Phosphorylation: Electron transfer through the cytochrome system liberating free energy which is transformed into high-energy phosphate bonds. [NIH]

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Oxidative Stress: A disturbance in the prooxidant-antioxidant balance in favor of the former, leading to potential damage. Indicators of oxidative stress include damaged DNA bases, protein oxidation products, and lipid peroxidation products (Sies, Oxidative Stress, 1991, pxv-xvi). [NIH] Oxygen Consumption: The oxygen consumption is determined by calculating the difference between the amount of oxygen inhaled and exhaled. [NIH] Pachymeningitis: Inflammation of the dura mater of the brain, the spinal cord or the optic nerve. [NIH] Paclitaxel: Antineoplastic agent isolated from the bark of the Pacific yew tree, Taxus brevifolia. Paclitaxel stabilizes microtubules in their polymerized form and thus mimics the action of the proto-oncogene proteins c-mos. [NIH] Palliative: 1. Affording relief, but not cure. 2. An alleviating medicine. [EU] Pancreas: A mixed exocrine and endocrine gland situated transversely across the posterior abdominal wall in the epigastric and hypochondriac regions. The endocrine portion is comprised of the Islets of Langerhans, while the exocrine portion is a compound acinar gland that secretes digestive enzymes. [NIH] Pancreatic: Having to do with the pancreas. [NIH] Pancreatic cancer: Cancer of the pancreas, a salivary gland of the abdomen. [NIH] Pancreatic Juice: The fluid containing digestive enzymes secreted by the pancreas in response to food in the duodenum. [NIH] Paneth Cells: Epithelial cells found in the basal part of the intestinal glands (Crypts of Lieberkuhn). Paneth cells synthesize and secrete lysozyme and cryptdins. [NIH] Papain: A proteolytic enzyme obtained from Carica papaya. It is also the name used for a purified mixture of papain and chymopapain that is used as a topical enzymatic debriding agent. EC 3.4.22.2. [NIH] Papillomavirus: A genus of Papovaviridae causing proliferation of the epithelium, which may lead to malignancy. A wide range of animals are infected including humans, chimpanzees, cattle, rabbits, dogs, and horses. [NIH] Paralysis: Loss of ability to move all or part of the body. [NIH] Parasite: An animal or a plant that lives on or in an organism of another species and gets at least some of its nutrition from that other organism. [NIH] Parasitic: Having to do with or being a parasite. A parasite is an animal or a plant that lives on or in an organism of another species and gets at least some of its nutrients from it. [NIH] Parasitic Diseases: Infections or infestations with parasitic organisms. They are often contracted through contact with an intermediate vector, but may occur as the result of direct exposure. [NIH] Paratyphoid Fever: A prolonged febrile illness commonly caused by serotypes of Salmonella paratyphi. It is similar to typhoid fever but less severe. [NIH] Paroxysmal: Recurring in paroxysms (= spasms or seizures). [EU] Partial remission: The shrinking, but not complete disappearance, of a tumor in response to therapy. Also called partial response. [NIH] Particle: A tiny mass of material. [EU] Patch: A piece of material used to cover or protect a wound, an injured part, etc.: a patch over the eye. [NIH] Pathogen: Any disease-producing microorganism. [EU]

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Pathogenesis: The cellular events and reactions that occur in the development of disease. [NIH]

Pathologic: 1. Indicative of or caused by a morbid condition. 2. Pertaining to pathology (= branch of medicine that treats the essential nature of the disease, especially the structural and functional changes in tissues and organs of the body caused by the disease). [EU] Pathologic Processes: The abnormal mechanisms and forms involved in the dysfunctions of tissues and organs. [NIH] Pathologies: The study of abnormality, especially the study of diseases. [NIH] Pathophysiology: Altered functions in an individual or an organ due to disease. [NIH] Patient Education: The teaching or training of patients concerning their own health needs. [NIH]

Pectins: High molecular weight polysaccharides present in the cell walls of all plants. Pectins cement cell walls together. They are used as emulsifiers and stabilizers in the food industry. They have been tried for a variety of therpeutic uses including as antidiarreals, where they are now generally considered ineffective, and in the treatment of hypercholesterolemia. [NIH] Pediococcus: A genus of gram-positive, facultatively anaerobic bacteria whose growth is dependent on the presence of a fermentable carbohydrate. No endospores are produced. Its organisms are found in fermenting plant products and are nonpathogenic to plants and animals, including humans. [NIH] Pelvic: Pertaining to the pelvis. [EU] Penicillin: An antibiotic drug used to treat infection. [NIH] Penis: The external reproductive organ of males. It is composed of a mass of erectile tissue enclosed in three cylindrical fibrous compartments. Two of the three compartments, the corpus cavernosa, are placed side-by-side along the upper part of the organ. The third compartment below, the corpus spongiosum, houses the urethra. [NIH] Pepsin: An enzyme made in the stomach that breaks down proteins. [NIH] Pepsin A: Formed from pig pepsinogen by cleavage of one peptide bond. The enzyme is a single polypeptide chain and is inhibited by methyl 2-diaazoacetamidohexanoate. It cleaves peptides preferentially at the carbonyl linkages of phenylalanine or leucine and acts as the principal digestive enzyme of gastric juice. [NIH] Peptide: Any compound consisting of two or more amino acids, the building blocks of proteins. Peptides are combined to make proteins. [NIH] Peptide Elongation Factors: Protein factors uniquely required during the elongation phase of protein synthesis. [NIH] Peptide Hydrolases: A subclass of enzymes from the hydrolase class that catalyze the hydrolysis of peptide bonds. Exopeptidases and endopeptidases make up the sub-subclasses for this group. EC 3.4. [NIH] Perforation: 1. The act of boring or piercing through a part. 2. A hole made through a part or substance. [EU] Pericarditis: Inflammation of the pericardium. [EU] Pericardium: The fibroserous sac surrounding the heart and the roots of the great vessels. [NIH]

Perineum: The area between the anus and the sex organs. [NIH] Peripheral blood: Blood circulating throughout the body. [NIH]

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Peripheral Nerves: The nerves outside of the brain and spinal cord, including the autonomic, cranial, and spinal nerves. Peripheral nerves contain non-neuronal cells and connective tissue as well as axons. The connective tissue layers include, from the outside to the inside, the epineurium, the perineurium, and the endoneurium. [NIH] Peripheral Nervous System: The nervous system outside of the brain and spinal cord. The peripheral nervous system has autonomic and somatic divisions. The autonomic nervous system includes the enteric, parasympathetic, and sympathetic subdivisions. The somatic nervous system includes the cranial and spinal nerves and their ganglia and the peripheral sensory receptors. [NIH] Periplasm: The space between the inner and outer membranes of a cell that is shared with the cell wall. [NIH] Peritoneal: Having to do with the peritoneum (the tissue that lines the abdominal wall and covers most of the organs in the abdomen). [NIH] Peritoneal Cavity: The space enclosed by the peritoneum. It is divided into two portions, the greater sac and the lesser sac or omental bursa, which lies behind the stomach. The two sacs are connected by the foramen of Winslow, or epiploic foramen. [NIH] Peritoneum: Endothelial lining of the abdominal cavity, the parietal peritoneum covering the inside of the abdominal wall and the visceral peritoneum covering the bowel, the mesentery, and certain of the organs. The portion that covers the bowel becomes the serosal layer of the bowel wall. [NIH] Peritonitis: Inflammation of the peritoneum; a condition marked by exudations in the peritoneum of serum, fibrin, cells, and pus. It is attended by abdominal pain and tenderness, constipation, vomiting, and moderate fever. [EU] Peroxide: Chemical compound which contains an atom group with two oxygen atoms tied to each other. [NIH] Petrolatum: A colloidal system of semisolid hydrocarbons obtained from petroleum. It is used as an ointment base, topical protectant, and lubricant. [NIH] Petroleum: Naturally occurring complex liquid hydrocarbons which, after distillation, yield combustible fuels, petrochemicals, and lubricants. [NIH] PH: The symbol relating the hydrogen ion (H+) concentration or activity of a solution to that of a given standard solution. Numerically the pH is approximately equal to the negative logarithm of H+ concentration expressed in molarity. pH 7 is neutral; above it alkalinity increases and below it acidity increases. [EU] Phagocyte: An immune system cell that can surround and kill microorganisms and remove dead cells. Phagocytes include macrophages. [NIH] Phagocytosis: The engulfing of microorganisms, other cells, and foreign particles by phagocytic cells. [NIH] Pharmacokinetics: Dynamic and kinetic mechanisms of exogenous chemical and drug absorption, biotransformation, distribution, release, transport, uptake, and elimination as a function of dosage, and extent and rate of metabolic processes. It includes toxicokinetics, the pharmacokinetic mechanism of the toxic effects of a substance. [NIH] Pharmacologic: Pertaining to pharmacology or to the properties and reactions of drugs. [EU] Pharyngitis: Inflammation of the throat. [NIH] Phenolphthalein: An acid-base indicator which is colorless in acid solution, but turns pink to red as the solution becomes alkaline. It is used medicinally as a cathartic. [NIH] Phenotype: The outward appearance of the individual. It is the product of interactions

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between genes and between the genotype and the environment. This includes the killer phenotype, characteristic of yeasts. [NIH] Phenylalanine: An aromatic amino acid that is essential in the animal diet. It is a precursor of melanin, dopamine, noradrenalin, and thyroxine. [NIH] Phosphogluconate Dehydrogenase: An enzyme of the oxidoreductase class that catalyzes the reaction 6-phospho-D-gluconate and NADP+ to yield D-ribulose 5-phosphate, carbon dioxide, and NADPH. The reaction is a step in the pentose phosphate pathway of glucose metabolism. (From Dorland, 27th ed) EC 1.1.1.43. [NIH] Phospholipases: A class of enzymes that catalyze the hydrolysis of phosphoglycerides or glycerophosphatidates. EC 3.1.-. [NIH] Phospholipids: Lipids containing one or more phosphate groups, particularly those derived from either glycerol (phosphoglycerides; glycerophospholipids) or sphingosine (sphingolipids). They are polar lipids that are of great importance for the structure and function of cell membranes and are the most abundant of membrane lipids, although not stored in large amounts in the system. [NIH] Phosphoric Monoester Hydrolases: A group of hydrolases which catalyze the hydrolysis of monophosphoric esters with the production of one mole of orthophosphate. EC 3.1.3. [NIH] Phosphorus: A non-metallic element that is found in the blood, muscles, nevers, bones, and teeth, and is a component of adenosine triphosphate (ATP; the primary energy source for the body's cells.) [NIH] Phosphorylase: An enzyme of the transferase class that catalyzes the phosphorylysis of a terminal alpha-1,4-glycosidic bond at the non-reducing end of a glycogen molecule, releasing a glucose 1-phosphate residue. Phosphorylase should be qualified by the natural substance acted upon. EC 2.4.1.1. [NIH] Phosphorylated: Attached to a phosphate group. [NIH] Phosphorylation: The introduction of a phosphoryl group into a compound through the formation of an ester bond between the compound and a phosphorus moiety. [NIH] Photocoagulation: Using a special strong beam of light (laser) to seal off bleeding blood vessels such as in the eye. The laser can also burn away blood vessels that should not have grown in the eye. This is the main treatment for diabetic retinopathy. [NIH] Photoreceptors: Cells specialized to detect and transduce light. [NIH] Phylogeny: The relationships of groups of organisms as reflected by their evolutionary history. [NIH] Physiologic: Having to do with the functions of the body. When used in the phrase "physiologic age," it refers to an age assigned by general health, as opposed to calendar age. [NIH]

Physiology: The science that deals with the life processes and functions of organismus, their cells, tissues, and organs. [NIH] Pigment: A substance that gives color to tissue. Pigments are responsible for the color of skin, eyes, and hair. [NIH] Pituitary Gland: A small, unpaired gland situated in the sella turcica tissue. It is connected to the hypothalamus by a short stalk. [NIH] Placenta: A highly vascular fetal organ through which the fetus absorbs oxygen and other nutrients and excretes carbon dioxide and other wastes. It begins to form about the eighth day of gestation when the blastocyst adheres to the decidua. [NIH] Plant Diseases: Diseases of plants. [NIH]

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Plant Growth Regulators: Any of the hormones produced naturally in plants and active in controlling growth and other functions. There are three primary classes: auxins, cytokinins, and gibberellins. [NIH] Plant Proteins: Proteins found in plants (flowers, herbs, shrubs, trees, etc.). The concept does not include proteins found in vegetables for which vegetable proteins is available. [NIH] Plants: Multicellular, eukaryotic life forms of the kingdom Plantae. They are characterized by a mainly photosynthetic mode of nutrition; essentially unlimited growth at localized regions of cell divisions (meristems); cellulose within cells providing rigidity; the absence of organs of locomotion; absense of nervous and sensory systems; and an alteration of haploid and diploid generations. [NIH] Plasma: The clear, yellowish, fluid part of the blood that carries the blood cells. The proteins that form blood clots are in plasma. [NIH] Plasma cells: A type of white blood cell that produces antibodies. [NIH] Plasma Exchange: Removal of plasma and replacement with various fluids, e.g., fresh frozen plasma, plasma protein fractions (PPF), albumin preparations, dextran solutions, saline. Used in treatment of autoimmune diseases, immune complex diseases, diseases of excess plasma factors, and other conditions. [NIH] Plasma protein: One of the hundreds of different proteins present in blood plasma, including carrier proteins ( such albumin, transferrin, and haptoglobin), fibrinogen and other coagulation factors, complement components, immunoglobulins, enzyme inhibitors, precursors of substances such as angiotension and bradykinin, and many other types of proteins. [EU] Plasmid: An autonomously replicating, extra-chromosomal DNA molecule found in many bacteria. Plasmids are widely used as carriers of cloned genes. [NIH] Plasmin: A product of the lysis of plasminogen (profibrinolysin) by plasminogen activators. It is composed of two polypeptide chains, light (B) and heavy (A), with a molecular weight of 75,000. It is the major proteolytic enzyme involved in blood clot retraction or the lysis of fibrin and quickly inactivated by antiplasmins. EC 3.4.21.7. [NIH] Plasminogen: Precursor of fibrinolysin (plasmin). It is a single-chain beta-globulin of molecular weight 80-90,000 found mostly in association with fibrinogen in plasma; plasminogen activators change it to fibrinolysin. It is used in wound debriding and has been investigated as a thrombolytic agent. [NIH] Plasminogen Activators: A heterogeneous group of proteolytic enzymes that convert plasminogen to plasmin. They are concentrated in the lysosomes of most cells and in the vascular endothelium, particularly in the vessels of the microcirculation. EC 3.4.21.-. [NIH] Plastids: Self-replicating cytoplasmic organelles of plant and algal cells that contain pigments and may synthesize and accumulate various substances. Plastids are used in phylogenetic studies. [NIH] Platelet Activation: A series of progressive, overlapping events triggered by exposure of the platelets to subendothelial tissue. These events include shape change, adhesiveness, aggregation, and release reactions. When carried through to completion, these events lead to the formation of a stable hemostatic plug. [NIH] Platelet Aggregation: The attachment of platelets to one another. This clumping together can be induced by a number of agents (e.g., thrombin, collagen) and is part of the mechanism leading to the formation of a thrombus. [NIH] Platelet Count: A count of the number of platelets per unit volume in a sample of venous blood. [NIH]

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Platelets: A type of blood cell that helps prevent bleeding by causing blood clots to form. Also called thrombocytes. [NIH] Platinum: Platinum. A heavy, soft, whitish metal, resembling tin, atomic number 78, atomic weight 195.09, symbol Pt. (From Dorland, 28th ed) It is used in manufacturing equipment for laboratory and industrial use. It occurs as a black powder (platinum black) and as a spongy substance (spongy platinum) and may have been known in Pliny's time as "alutiae". [NIH]

Pleated: Particular three-dimensional pattern of amyloidoses. [NIH] Pleural: A circumscribed area of hyaline whorled fibrous tissue which appears on the surface of the parietal pleura, on the fibrous part of the diaphragm or on the pleura in the interlobar fissures. [NIH] Pleural cavity: A space enclosed by the pleura (thin tissue covering the lungs and lining the interior wall of the chest cavity). It is bound by thin membranes. [NIH] Pneumonitis: A disease caused by inhaling a wide variety of substances such as dusts and molds. Also called "farmer's disease". [NIH] Poisoning: A condition or physical state produced by the ingestion, injection or inhalation of, or exposure to a deleterious agent. [NIH] Polycystic: An inherited disorder characterized by many grape-like clusters of fluid-filled cysts that make both kidneys larger over time. These cysts take over and destroy working kidney tissue. PKD may cause chronic renal failure and end-stage renal disease. [NIH] Polyesters: Polymers of organic acids and alcohols, with ester linkages--usually polyethylene terephthalate; can be cured into hard plastic, films or tapes, or fibers which can be woven into fabrics, meshes or velours. [NIH] Polyethylene: A vinyl polymer made from ethylene. It can be branched or linear. Branched or low-density polyethylene is tough and pliable but not to the same degree as linear polyethylene. Linear or high-density polyethylene has a greater hardness and tensile strength. Polyethylene is used in a variety of products, including implants and prostheses. [NIH]

Polymerase: An enzyme which catalyses the synthesis of DNA using a single DNA strand as a template. The polymerase copies the template in the 5'-3'direction provided that sufficient quantities of free nucleotides, dATP and dTTP are present. [NIH] Polymerase Chain Reaction: In vitro method for producing large amounts of specific DNA or RNA fragments of defined length and sequence from small amounts of short oligonucleotide flanking sequences (primers). The essential steps include thermal denaturation of the double-stranded target molecules, annealing of the primers to their complementary sequences, and extension of the annealed primers by enzymatic synthesis with DNA polymerase. The reaction is efficient, specific, and extremely sensitive. Uses for the reaction include disease diagnosis, detection of difficult-to-isolate pathogens, mutation analysis, genetic testing, DNA sequencing, and analyzing evolutionary relationships. [NIH] Polymers: Compounds formed by the joining of smaller, usually repeating, units linked by covalent bonds. These compounds often form large macromolecules (e.g., polypeptides, proteins, plastics). [NIH] Polymorphic: Occurring in several or many forms; appearing in different forms at different stages of development. [EU] Polymorphism: The occurrence together of two or more distinct forms in the same population. [NIH] Polypeptide: A peptide which on hydrolysis yields more than two amino acids; called

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tripeptides, tetrapeptides, etc. according to the number of amino acids contained. [EU] Polyposis: The development of numerous polyps (growths that protrude from a mucous membrane). [NIH] Polysaccharide: A type of carbohydrate. It contains sugar molecules that are linked together chemically. [NIH] Polyunsaturated fat: An unsaturated fat found in greatest amounts in foods derived from plants, including safflower, sunflower, corn, and soybean oils. [NIH] Population Dynamics: The pattern of any process, or the interrelationship of phenomena, which affects growth or change within a population. [NIH] Porphyria: A group of disorders characterized by the excessive production of porphyrins or their precursors that arises from abnormalities in the regulation of the porphyrin-heme pathway. The porphyrias are usually divided into three broad groups, erythropoietic, hepatic, and erythrohepatic, according to the major sites of abnormal porphyrin synthesis. [NIH]

Porphyrins: A group of compounds containing the porphin structure, four pyrrole rings connected by methine bridges in a cyclic configuration to which a variety of side chains are attached. The nature of the side chain is indicated by a prefix, as uroporphyrin, hematoporphyrin, etc. The porphyrins, in combination with iron, form the heme component in biologically significant compounds such as hemoglobin and myoglobin. [NIH] Posterior: Situated in back of, or in the back part of, or affecting the back or dorsal surface of the body. In lower animals, it refers to the caudal end of the body. [EU] Postmenopausal: Refers to the time after menopause. Menopause is the time in a woman's life when menstrual periods stop permanently; also called "change of life." [NIH] Postnatal: Occurring after birth, with reference to the newborn. [EU] Postoperative: After surgery. [NIH] Postsynaptic: Nerve potential generated by an inhibitory hyperpolarizing stimulation. [NIH] Post-translational: The cleavage of signal sequence that directs the passage of the protein through a cell or organelle membrane. [NIH] Potentiates: A degree of synergism which causes the exposure of the organism to a harmful substance to worsen a disease already contracted. [NIH] Potentiation: An overall effect of two drugs taken together which is greater than the sum of the effects of each drug taken alone. [NIH] Practice Guidelines: Directions or principles presenting current or future rules of policy for the health care practitioner to assist him in patient care decisions regarding diagnosis, therapy, or related clinical circumstances. The guidelines may be developed by government agencies at any level, institutions, professional societies, governing boards, or by the convening of expert panels. The guidelines form a basis for the evaluation of all aspects of health care and delivery. [NIH] Precipitation: The act or process of precipitating. [EU] Precursor: Something that precedes. In biological processes, a substance from which another, usually more active or mature substance is formed. In clinical medicine, a sign or symptom that heralds another. [EU] Predisposition: A latent susceptibility to disease which may be activated under certain conditions, as by stress. [EU] Premenopausal: Refers to the time before menopause. Menopause is the time of life when a women's menstrual periods stop permanently; also called "change of life." [NIH]

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Presumptive: A treatment based on an assumed diagnosis, prior to receiving confirmatory laboratory test results. [NIH] Prevalence: The total number of cases of a given disease in a specified population at a designated time. It is differentiated from incidence, which refers to the number of new cases in the population at a given time. [NIH] Prickle: Several layers of the epidermis where the individual cells are connected by cell bridges. [NIH] Primary Biliary Cirrhosis: A chronic liver disease. Slowly destroys the bile ducts in the liver. This prevents release of bile. Long-term irritation of the liver may cause scarring and cirrhosis in later stages of the disease. [NIH] Probe: An instrument used in exploring cavities, or in the detection and dilatation of strictures, or in demonstrating the potency of channels; an elongated instrument for exploring or sounding body cavities. [NIH] Prodrug: A substance that gives rise to a pharmacologically active metabolite, although not itself active (i. e. an inactive precursor). [NIH] Progeny: The offspring produced in any generation. [NIH] Progesterone: Pregn-4-ene-3,20-dione. The principal progestational hormone of the body, secreted by the corpus luteum, adrenal cortex, and placenta. Its chief function is to prepare the uterus for the reception and development of the fertilized ovum. It acts as an antiovulatory agent when administered on days 5-25 of the menstrual cycle. [NIH] Progression: Increase in the size of a tumor or spread of cancer in the body. [NIH] Progressive: Advancing; going forward; going from bad to worse; increasing in scope or severity. [EU] Projection: A defense mechanism, operating unconsciously, whereby that which is emotionally unacceptable in the self is rejected and attributed (projected) to others. [NIH] Prokaryotic Cells: Cells, such as those of bacteria and the blue green algae, which lack a nuclear membrane so that the nuclear material is either scattered in the cytoplasm or collected in a nucleoid region. [NIH] Proline: A non-essential amino acid that is synthesized from glutamic acid. It is an essential component of collagen and is important for proper functioning of joints and tendons. [NIH] Promoter: A chemical substance that increases the activity of a carcinogenic process. [NIH] Promotor: In an operon, a nucleotide sequence located at the operator end which contains all the signals for the correct initiation of genetic transcription by the RNA polymerase holoenzyme and determines the maximal rate of RNA synthesis. [NIH] Prone: Having the front portion of the body downwards. [NIH] Proneness: Susceptibility to accidents due to human factors. [NIH] Prophase: The first phase of cell division, in which the chromosomes become visible, the nucleus starts to lose its identity, the spindle appears, and the centrioles migrate toward opposite poles. [NIH] Prophylaxis: An attempt to prevent disease. [NIH] Proportional: Being in proportion : corresponding in size, degree, or intensity, having the same or a constant ratio; of, relating to, or used in determining proportions. [EU] Prostate: A gland in males that surrounds the neck of the bladder and the urethra. It secretes a substance that liquifies coagulated semen. It is situated in the pelvic cavity behind the lower part of the pubic symphysis, above the deep layer of the triangular ligament, and rests

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upon the rectum. [NIH] Protease: Proteinase (= any enzyme that catalyses the splitting of interior peptide bonds in a protein). [EU] Protein C: A vitamin-K dependent zymogen present in the blood, which, upon activation by thrombin and thrombomodulin exerts anticoagulant properties by inactivating factors Va and VIIIa at the rate-limiting steps of thrombin formation. [NIH] Protein Conformation: The characteristic 3-dimensional shape of a protein, including the secondary, supersecondary (motifs), tertiary (domains) and quaternary structure of the peptide chain. Quaternary protein structure describes the conformation assumed by multimeric proteins (aggregates of more than one polypeptide chain). [NIH] Protein Engineering: Procedures by which nonrandom single-site changes are introduced into structural genes (site-specific mutagenesis) in order to produce mutant genes which can be coupled to promoters that direct the synthesis of a specifically altered protein, which is then analyzed for structural and functional properties and then compared with the predicted and sought-after properties. The design of the protein may be assisted by computer graphic technology and other advanced molecular modeling techniques. [NIH] Protein Folding: A rapid biochemical reaction involved in the formation of proteins. It begins even before a protein has been completely synthesized and proceeds through discrete intermediates (primary, secondary, and tertiary structures) before the final structure (quaternary structure) is developed. [NIH] Protein S: The vitamin K-dependent cofactor of activated protein C. Together with protein C, it inhibits the action of factors VIIIa and Va. A deficiency in protein S can lead to recurrent venous and arterial thrombosis. [NIH] Protein Subunits: Single chains of amino acids that are the units of a multimeric protein. They can be identical or non-identical subunits. [NIH] Proteins: Polymers of amino acids linked by peptide bonds. The specific sequence of amino acids determines the shape and function of the protein. [NIH] Proteoglycans: Glycoproteins which have a very high polysaccharide content. [NIH] Proteolytic: 1. Pertaining to, characterized by, or promoting proteolysis. 2. An enzyme that promotes proteolysis (= the splitting of proteins by hydrolysis of the peptide bonds with formation of smaller polypeptides). [EU] Prothrombin: A plasma protein that is the inactive precursor of thrombin. It is converted to thrombin by a prothrombin activator complex consisting of factor Xa, factor V, phospholipid, and calcium ions. Deficiency of prothrombin leads to hypoprothrombinemia. [NIH]

Protocol: The detailed plan for a clinical trial that states the trial's rationale, purpose, drug or vaccine dosages, length of study, routes of administration, who may participate, and other aspects of trial design. [NIH] Proton Pump: Integral membrane proteins that transport protons across a membrane against a concentration gradient. This transport is driven by hydrolysis of ATP by H(+)transporting ATP synthase. [NIH] Protons: Stable elementary particles having the smallest known positive charge, found in the nuclei of all elements. The proton mass is less than that of a neutron. A proton is the nucleus of the light hydrogen atom, i.e., the hydrogen ion. [NIH] Proto-Oncogene Proteins: Products of proto-oncogenes. Normally they do not have oncogenic or transforming properties, but are involved in the regulation or differentiation of cell growth. They often have protein kinase activity. [NIH]

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Proto-Oncogene Proteins c-mos: Cellular proteins encoded by the c-mos genes. They function in the cell cycle to maintain maturation promoting factor in the active state and have protein-serine/threonine kinase activity. Oncogenic transformation can take place when c-mos proteins are expressed at the wrong time. [NIH] Protozoa: A subkingdom consisting of unicellular organisms that are the simplest in the animal kingdom. Most are free living. They range in size from submicroscopic to macroscopic. Protozoa are divided into seven phyla: Sarcomastigophora, Labyrinthomorpha, Apicomplexa, Microspora, Ascetospora, Myxozoa, and Ciliophora. [NIH] Psoralen: A substance that binds to the DNA in cells and stops them from multiplying. It is being studied in the treatment of graft-versus-host disease and is used in the treatment of psoriasis and vitiligo. [NIH] Psoriasis: A common genetically determined, chronic, inflammatory skin disease characterized by rounded erythematous, dry, scaling patches. The lesions have a predilection for nails, scalp, genitalia, extensor surfaces, and the lumbosacral region. Accelerated epidermopoiesis is considered to be the fundamental pathologic feature in psoriasis. [NIH] Psychology: The science dealing with the study of mental processes and behavior in man and animals. [NIH] Public Health: Branch of medicine concerned with the prevention and control of disease and disability, and the promotion of physical and mental health of the population on the international, national, state, or municipal level. [NIH] Public Policy: A course or method of action selected, usually by a government, from among alternatives to guide and determine present and future decisions. [NIH] Publishing: "The business or profession of the commercial production and issuance of literature" (Webster's 3d). It includes the publisher, publication processes, editing and editors. Production may be by conventional printing methods or by electronic publishing. [NIH]

Pulmonary: Relating to the lungs. [NIH] Pulmonary Edema: An accumulation of an excessive amount of watery fluid in the lungs, may be caused by acute exposure to dangerous concentrations of irritant gasses. [NIH] Pulse: The rhythmical expansion and contraction of an artery produced by waves of pressure caused by the ejection of blood from the left ventricle of the heart as it contracts. [NIH]

Purifying: Respiratory equipment whose function is to remove contaminants from otherwise wholesome air. [NIH] Purines: A series of heterocyclic compounds that are variously substituted in nature and are known also as purine bases. They include adenine and guanine, constituents of nucleic acids, as well as many alkaloids such as caffeine and theophylline. Uric acid is the metabolic end product of purine metabolism. [NIH] Purpura: Purplish or brownish red discoloration, easily visible through the epidermis, caused by hemorrhage into the tissues. [NIH] Pustular: Pertaining to or of the nature of a pustule; consisting of pustules (= a visible collection of pus within or beneath the epidermis). [EU] Putrescine: A toxic diamine formed by putrefaction from the decarboxylation of arginine and ornithine. [NIH] Pyelonephritis: Inflammation of the kidney and its pelvis, beginning in the interstitium and rapidly extending to involve the tubules, glomeruli, and blood vessels; due to bacterial

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infection. [EU] Pyogenic: Producing pus; pyopoietic (= liquid inflammation product made up of cells and a thin fluid called liquor puris). [EU] Pyridoxal: 3-Hydroxy-5-(hydroxymethyl)-2-methyl-4- pyridinecarboxaldehyde. [NIH] Quality of Life: A generic concept reflecting concern with the modification and enhancement of life attributes, e.g., physical, political, moral and social environment. [NIH] Quaternary: 1. Fourth in order. 2. Containing four elements or groups. [EU] Quinones: Hydrocarbon rings which contain two ketone moieties in any position. They can be substituted in any position except at the ketone groups. [NIH] Radiation: Emission or propagation of electromagnetic energy (waves/rays), or the waves/rays themselves; a stream of electromagnetic particles (electrons, neutrons, protons, alpha particles) or a mixture of these. The most common source is the sun. [NIH] Radioactive: Giving off radiation. [NIH] Radioisotope: An unstable element that releases radiation as it breaks down. Radioisotopes can be used in imaging tests or as a treatment for cancer. [NIH] Randomized: Describes an experiment or clinical trial in which animal or human subjects are assigned by chance to separate groups that compare different treatments. [NIH] Reactivation: The restoration of activity to something that has been inactivated. [EU] Reactive Oxygen Species: Reactive intermediate oxygen species including both radicals and non-radicals. These substances are constantly formed in the human body and have been shown to kill bacteria and inactivate proteins, and have been implicated in a number of diseases. Scientific data exist that link the reactive oxygen species produced by inflammatory phagocytes to cancer development. [NIH] Reading Frames: The sequence of codons by which translation may occur. A segment of mRNA 5'AUCCGA3' could be translated in three reading frames, 5'AUC. or 5'UCC. or 5'CCG., depending on the location of the start codon. [NIH] Reagent: A substance employed to produce a chemical reaction so as to detect, measure, produce, etc., other substances. [EU] Receptor: A molecule inside or on the surface of a cell that binds to a specific substance and causes a specific physiologic effect in the cell. [NIH] Recombinant: A cell or an individual with a new combination of genes not found together in either parent; usually applied to linked genes. [EU] Recombinant Proteins: Proteins prepared by recombinant DNA technology. [NIH] Recombination: The formation of new combinations of genes as a result of segregation in crosses between genetically different parents; also the rearrangement of linked genes due to crossing-over. [NIH] Reconstitution: 1. A type of regeneration in which a new organ forms by the rearrangement of tissues rather than from new formation at an injured surface. 2. The restoration to original form of a substance previously altered for preservation and storage, as the restoration to a liquid state of blood serum or plasma that has been dried and stored. [EU] Rectal: By or having to do with the rectum. The rectum is the last 8 to 10 inches of the large intestine and ends at the anus. [NIH] Rectum: The last 8 to 10 inches of the large intestine. [NIH] Red blood cells: RBCs. Cells that carry oxygen to all parts of the body. Also called erythrocytes. [NIH]

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Red Nucleus: A pinkish-yellow portion of the midbrain situated in the rostral mesencephalic tegmentum. It receives a large projection from the contralateral half of the cerebellum via the superior cerebellar peduncle and a projection from the ipsilateral motor cortex. [NIH] Reductase: Enzyme converting testosterone to dihydrotestosterone. [NIH] Refer: To send or direct for treatment, aid, information, de decision. [NIH] Refraction: A test to determine the best eyeglasses or contact lenses to correct a refractive error (myopia, hyperopia, or astigmatism). [NIH] Refractory: Not readily yielding to treatment. [EU] Regeneration: The natural renewal of a structure, as of a lost tissue or part. [EU] Regimen: A treatment plan that specifies the dosage, the schedule, and the duration of treatment. [NIH] Regulon: In eukaryotes, a genetic unit consisting of a noncontiguous group of genes under the control of a single regulator gene. In bacteria, regulons are global regulatory systems involved in the interplay of pleiotropic regulatory domains. These regulatory systems consist of several operons. [NIH] Rehydration: The restoration of water or of fluid content to a body or to substance which has become dehydrated. [EU] Remission: A decrease in or disappearance of signs and symptoms of cancer. In partial remission, some, but not all, signs and symptoms of cancer have disappeared. In complete remission, all signs and symptoms of cancer have disappeared, although there still may be cancer in the body. [NIH] Remission Induction: Therapeutic act or process that initiates a response to a complete or partial remission level. [NIH] Remission induction therapy: The initial chemotherapy a person receives to bring about a remission. [NIH] Renal failure: Progressive renal insufficiency and uremia, due to irreversible and progressive renal glomerular tubular or interstitial disease. [NIH] Renal tubular: A defect in the kidneys that hinders their normal excretion of acids. Failure to excrete acids can lead to weak bones, kidney stones, and poor growth in children. [NIH] Renin: An enzyme which is secreted by the kidney and is formed from prorenin in plasma and kidney. The enzyme cleaves the Leu-Leu bond in angiotensinogen to generate angiotensin I. EC 3.4.23.15. (Formerly EC 3.4.99.19). [NIH] Repressor: Any of the specific allosteric protein molecules, products of regulator genes, which bind to the operator of operons and prevent RNA polymerase from proceeding into the operon to transcribe messenger RNA. [NIH] Research Design: A plan for collecting and utilizing data so that desired information can be obtained with sufficient precision or so that an hypothesis can be tested properly. [NIH] Resolving: The ability of the eye or of a lens to make small objects that are close together, separately visible; thus revealing the structure of an object. [NIH] Resorption: The loss of substance through physiologic or pathologic means, such as loss of dentin and cementum of a tooth, or of the alveolar process of the mandible or maxilla. [EU] Respiration: The act of breathing with the lungs, consisting of inspiration, or the taking into the lungs of the ambient air, and of expiration, or the expelling of the modified air which contains more carbon dioxide than the air taken in (Blakiston's Gould Medical Dictionary, 4th ed.). This does not include tissue respiration (= oxygen consumption) or cell respiration

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(= cell respiration). [NIH] Respiratory distress syndrome: A lung disease that occurs primarily in premature infants; the newborn must struggle for each breath and blueing of its skin reflects the baby's inability to get enough oxygen. [NIH] Response Elements: Nucleotide sequences, usually upstream, which are recognized by specific regulatory transcription factors, thereby causing gene response to various regulatory agents. These elements may be found in both promotor and enhancer regions. [NIH]

Restoration: Broad term applied to any inlay, crown, bridge or complete denture which restores or replaces loss of teeth or oral tissues. [NIH] Retina: The ten-layered nervous tissue membrane of the eye. It is continuous with the optic nerve and receives images of external objects and transmits visual impulses to the brain. Its outer surface is in contact with the choroid and the inner surface with the vitreous body. The outer-most layer is pigmented, whereas the inner nine layers are transparent. [NIH] Retinal: 1. Pertaining to the retina. 2. The aldehyde of retinol, derived by the oxidative enzymatic splitting of absorbed dietary carotene, and having vitamin A activity. In the retina, retinal combines with opsins to form visual pigments. One isomer, 11-cis retinal combines with opsin in the rods (scotopsin) to form rhodopsin, or visual purple. Another, all-trans retinal (trans-r.); visual yellow; xanthopsin) results from the bleaching of rhodopsin by light, in which the 11-cis form is converted to the all-trans form. Retinal also combines with opsins in the cones (photopsins) to form the three pigments responsible for colour vision. Called also retinal, and retinene1. [EU] Retinoblastoma: An eye cancer that most often occurs in children younger than 5 years. It occurs in hereditary and nonhereditary (sporadic) forms. [NIH] Retinol: Vitamin A. It is essential for proper vision and healthy skin and mucous membranes. Retinol is being studied for cancer prevention; it belongs to the family of drugs called retinoids. [NIH] Retrovirus: A member of a group of RNA viruses, the RNA of which is copied during viral replication into DNA by reverse transcriptase. The viral DNA is then able to be integrated into the host chromosomal DNA. [NIH] Reversion: A return to the original condition, e. g. the reappearance of the normal or wild type in previously mutated cells, tissues, or organisms. [NIH] Rheumatism: A group of disorders marked by inflammation or pain in the connective tissue structures of the body. These structures include bone, cartilage, and fat. [NIH] Rheumatoid: Resembling rheumatism. [EU] Rheumatoid arthritis: A form of arthritis, the cause of which is unknown, although infection, hypersensitivity, hormone imbalance and psychologic stress have been suggested as possible causes. [NIH] Rhinitis: Inflammation of the mucous membrane of the nose. [NIH] Ribonuclease: RNA-digesting enzyme. [NIH] Ribonucleic acid: RNA. One of the two nucleic acids found in all cells. The other is deoxyribonucleic acid (DNA). Ribonucleic acid transfers genetic information from DNA to proteins produced by the cell. [NIH] Ribose: A pentose active in biological systems usually in its D-form. [NIH] Ribosome: A granule of protein and RNA, synthesized in the nucleolus and found in the cytoplasm of cells. Ribosomes are the main sites of protein synthesis. Messenger RNA

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attaches to them and there receives molecules of transfer RNA bearing amino acids. [NIH] Rigidity: Stiffness or inflexibility, chiefly that which is abnormal or morbid; rigor. [EU] Risk factor: A habit, trait, condition, or genetic alteration that increases a person's chance of developing a disease. [NIH] Ristocetin: An antibiotic mixture of two components, A and B, obtained from Nocardia lurida (or the same substance produced by any other means). It is no longer used clinically because of its toxicity. It causes platelet agglutination and blood coagulation and is used to assay those functions in vitro. [NIH] RNA: Ribonucleic acid. One of the two types of nucleic acids found in cells. The other is DNA (deoxyribonucleic acid). RNA plays a role in sending information from DNA to the protein-forming system of the cell. [NIH] Rod: A reception for vision, located in the retina. [NIH] Rotavirus: A genus of Reoviridae, causing acute gastroenteritis in birds and mammals, including humans. Transmission is horizontal and by environmental contamination. [NIH] Rubber: A high-molecular-weight polymeric elastomer derived from the milk juice (latex) of Hevea brasiliensis and other trees. It is a substance that can be stretched at room temperature to atleast twice its original length and after releasing the stress, retractrapidly, and recover its original dimensions fully. Synthetic rubber is made from many different chemicals, including styrene, acrylonitrile, ethylene, propylene, and isoprene. [NIH] Saline: A solution of salt and water. [NIH] Saliva: The clear, viscous fluid secreted by the salivary glands and mucous glands of the mouth. It contains mucins, water, organic salts, and ptylin. [NIH] Salivary: The duct that convey saliva to the mouth. [NIH] Salivary glands: Glands in the mouth that produce saliva. [NIH] Salmonella: A genus of gram-negative, facultatively anaerobic, rod-shaped bacteria that utilizes citrate as a sole carbon source. It is pathogenic for humans, causing enteric fevers, gastroenteritis, and bacteremia. Food poisoning is the most common clinical manifestation. Organisms within this genus are separated on the basis of antigenic characteristics, sugar fermentation patterns, and bacteriophage susceptibility. [NIH] Salmonella typhi: A serotype of Salmonella enterica which is the etiologic agent of typhoid fever. [NIH] Salmonella typhimurium: A serotype of Salmonella enterica that is a frequent agent of Salmonella gastroenteritis in humans. It also causes paratyphoid fever. [NIH] Saponins: Sapogenin glycosides. A type of glycoside widely distributed in plants. Each consists of a sapogenin as the aglycon moiety, and a sugar. The sapogenin may be a steroid or a triterpene and the sugar may be glucose, galactose, a pentose, or a methylpentose. Sapogenins are poisonous towards the lower forms of life and are powerful hemolytics when injected into the blood stream able to dissolve red blood cells at even extreme dilutions. [NIH] Saprophyte: A saprophytic (= whose nutrition involves uptake of dissolved organic material from decaying plant or animal matter) organism. [EU] Satellite: Applied to a vein which closely accompanies an artery for some distance; in cytogenetics, a chromosomal agent separated by a secondary constriction from the main body of the chromosome. [NIH] Saturated fat: A type of fat found in greatest amounts in foods from animals, such as fatty cuts of meat, poultry with the skin, whole-milk dairy products, lard, and in some vegetable

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oils, including coconut, palm kernel, and palm oils. Saturated fat raises blood cholesterol more than anything else eaten. On a Step I Diet, no more than 8 to 10 percent of total calories should come from saturated fat, and in the Step II Diet, less than 7 percent of the day's total calories should come from saturated fat. [NIH] Scarlet Fever: Infection with group A streptococci that is characterized by tonsillitis and pharyngitis. An erythematous rash is commonly present. [NIH] Sclerosis: A pathological process consisting of hardening or fibrosis of an anatomical structure, often a vessel or a nerve. [NIH] Screening: Checking for disease when there are no symptoms. [NIH] Sebaceous: Gland that secretes sebum. [NIH] Second Messenger Systems: Systems in which an intracellular signal is generated in response to an intercellular primary messenger such as a hormone or neurotransmitter. They are intermediate signals in cellular processes such as metabolism, secretion, contraction, phototransduction, and cell growth. Examples of second messenger systems are the adenyl cyclase-cyclic AMP system, the phosphatidylinositol diphosphate-inositol triphosphate system, and the cyclic GMP system. [NIH] Secondary tumor: Cancer that has spread from the organ in which it first appeared to another organ. For example, breast cancer cells may spread (metastasize) to the lungs and cause the growth of a new tumor. When this happens, the disease is called metastatic breast cancer, and the tumor in the lungs is called a secondary tumor. Also called secondary cancer. [NIH] Secretion: 1. The process of elaborating a specific product as a result of the activity of a gland; this activity may range from separating a specific substance of the blood to the elaboration of a new chemical substance. 2. Any substance produced by secretion. [EU] Secretory: Secreting; relating to or influencing secretion or the secretions. [NIH] Sedative: 1. Allaying activity and excitement. 2. An agent that allays excitement. [EU] Segregation: The separation in meiotic cell division of homologous chromosome pairs and their contained allelomorphic gene pairs. [NIH] Seizures: Clinical or subclinical disturbances of cortical function due to a sudden, abnormal, excessive, and disorganized discharge of brain cells. Clinical manifestations include abnormal motor, sensory and psychic phenomena. Recurrent seizures are usually referred to as epilepsy or "seizure disorder." [NIH] Selenium: An element with the atomic symbol Se, atomic number 34, and atomic weight 78.96. It is an essential micronutrient for mammals and other animals but is toxic in large amounts. Selenium protects intracellular structures against oxidative damage. It is an essential component of glutathione peroxidase. [NIH] Selenocysteine: A naturally occurring amino acid in both eukaryotic and prokaryotic organisms. It is found in tRNAs and in the catalytic site of some enzymes. The genes for glutathione peroxidase and formate dehydrogenase contain the TGA codon, which codes for this amino acid. [NIH] Selenomethionine: Diagnostic aid in pancreas function determination. [NIH] Semen: The thick, yellowish-white, viscid fluid secretion of male reproductive organs discharged upon ejaculation. In addition to reproductive organ secretions, it contains spermatozoa and their nutrient plasma. [NIH] Seminiferous tubule: Tube used to transport sperm made in the testes. [NIH] Semisynthetic: Produced by chemical manipulation of naturally occurring substances. [EU]

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Sensitization: 1. Administration of antigen to induce a primary immune response; priming; immunization. 2. Exposure to allergen that results in the development of hypersensitivity. 3. The coating of erythrocytes with antibody so that they are subject to lysis by complement in the presence of homologous antigen, the first stage of a complement fixation test. [EU] Sensor: A device designed to respond to physical stimuli such as temperature, light, magnetism or movement and transmit resulting impulses for interpretation, recording, movement, or operating control. [NIH] Sepsis: The presence of bacteria in the bloodstream. [NIH] Septal: An abscess occurring at the root of the tooth on the proximal surface. [NIH] Septic: Produced by or due to decomposition by microorganisms; putrefactive. [EU] Septicaemia: A term originally used to denote a putrefactive process in the body, but now usually referring to infection with pyogenic micro-organisms; a genus of Diptera; the severe type of infection in which the blood stream is invaded by large numbers of the causal. [NIH] Septum: A dividing wall or partition; a general term for such a structure. The term is often used alone to refer to the septal area or to the septum pellucidum. [EU] Septum Pellucidum: A triangular double membrane separating the anterior horns of the lateral ventricles of the brain. It is situated in the median plane and bounded by the corpus callosum and the body and columns of the fornix. [NIH] Sequencing: The determination of the order of nucleotides in a DNA or RNA chain. [NIH] Serine: A non-essential amino acid occurring in natural form as the L-isomer. It is synthesized from glycine or threonine. It is involved in the biosynthesis of purines, pyrimidines, and other amino acids. [NIH] Serologic: Analysis of a person's serum, especially specific immune or lytic serums. [NIH] Serotypes: A cause of haemorrhagic septicaemia (in cattle, sheep and pigs), fowl cholera of birds, pasteurellosis of rabbits, and gangrenous mastitis of ewes. It is also commonly found in atrophic rhinitis of pigs. [NIH] Serous: Having to do with serum, the clear liquid part of blood. [NIH] Serum: The clear liquid part of the blood that remains after blood cells and clotting proteins have been removed. [NIH] Serum Albumin: A major plasma protein that serves in maintaining the plasma colloidal osmotic pressure and transporting large organic anions. [NIH] Sex Determination: The biological characteristics which distinguish human beings as female or male. [NIH] Shedding: Release of infectious particles (e. g., bacteria, viruses) into the environment, for example by sneezing, by fecal excretion, or from an open lesion. [NIH] Shiga Toxin: A toxin produced by Shigella dysenteriae. It is the protype of class of toxins that inhibit protein synthesis by blocking the interaction of ribosomal RNA with peptide elongation factors. [NIH] Shock: The general bodily disturbance following a severe injury; an emotional or moral upset occasioned by some disturbing or unexpected experience; disruption of the circulation, which can upset all body functions: sometimes referred to as circulatory shock. [NIH]

Side effect: A consequence other than the one(s) for which an agent or measure is used, as the adverse effects produced by a drug, especially on a tissue or organ system other than the one sought to be benefited by its administration. [EU]

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Sigma Factor: A protein which is a subunit of RNA polymerase. It effects initiation of specific RNA chains from DNA. [NIH] Signal Recognition Particle: A cytosolic ribonucleoprotein complex that acts to induce elongation arrest of nascent presecretory and membrane proteins until the ribosome becomes associated with the rough endoplasmic reticulum. It consists of a 7S RNA and at least six polypeptide subunits (relative molecular masses 9, 14, 19, 54, 68, and 72K). [NIH] Signal Transduction: The intercellular or intracellular transfer of information (biological activation/inhibition) through a signal pathway. In each signal transduction system, an activation/inhibition signal from a biologically active molecule (hormone, neurotransmitter) is mediated via the coupling of a receptor/enzyme to a second messenger system or to an ion channel. Signal transduction plays an important role in activating cellular functions, cell differentiation, and cell proliferation. Examples of signal transduction systems are the GABA-postsynaptic receptor-calcium ion channel system, the receptor-mediated T-cell activation pathway, and the receptor-mediated activation of phospholipases. Those coupled to membrane depolarization or intracellular release of calcium include the receptormediated activation of cytotoxic functions in granulocytes and the synaptic potentiation of protein kinase activation. Some signal transduction pathways may be part of larger signal transduction pathways; for example, protein kinase activation is part of the platelet activation signal pathway. [NIH] Signs and Symptoms: Clinical manifestations that can be either objective when observed by a physician, or subjective when perceived by the patient. [NIH] Sil: The arithmetical average of the octave band sound pressure levels of a noise, centered on the frequencies 425, 850 and 1700 Hz together with the frequency 212 of the SIL in this band exceeds the others by 10 dB or more. [NIH] Silage: Fodder converted into succulent feed for livestock through processes of anaerobic fermentation (as in a silo). [NIH] Skeleton: The framework that supports the soft tissues of vertebrate animals and protects many of their internal organs. The skeletons of vertebrates are made of bone and/or cartilage. [NIH] Skull: The skeleton of the head including the bones of the face and the bones enclosing the brain. [NIH] Sludge: A clump of agglutinated red blood cells. [NIH] Small intestine: The part of the digestive tract that is located between the stomach and the large intestine. [NIH] Smooth muscle: Muscle that performs automatic tasks, such as constricting blood vessels. [NIH]

Sneezing: Sudden, forceful, involuntary expulsion of air from the nose and mouth caused by irritation to the mucous membranes of the upper respiratory tract. [NIH] Soft tissue: Refers to muscle, fat, fibrous tissue, blood vessels, or other supporting tissue of the body. [NIH] Solid tumor: Cancer of body tissues other than blood, bone marrow, or the lymphatic system. [NIH] Solvent: 1. Dissolving; effecting a solution. 2. A liquid that dissolves or that is capable of dissolving; the component of a solution that is present in greater amount. [EU] Somatic: 1. Pertaining to or characteristic of the soma or body. 2. Pertaining to the body wall in contrast to the viscera. [EU] Sorbitol: A polyhydric alcohol with about half the sweetness of sucrose. Sorbitol occurs

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naturally and is also produced synthetically from glucose. It was formerly used as a diuretic and may still be used as a laxative and in irrigating solutions for some surgical procedures. It is also used in many manufacturing processes, as a pharmaceutical aid, and in several research applications. [NIH] Soybean Oil: Oil from soybean or soybean plant. [NIH] Space Flight: Travel beyond the earth's atmosphere. [NIH] Spastic: 1. Of the nature of or characterized by spasms. 2. Hypertonic, so that the muscles are stiff and the movements awkward. 3. A person exhibiting spasticity, such as occurs in spastic paralysis or in cerebral palsy. [EU] Spasticity: A state of hypertonicity, or increase over the normal tone of a muscle, with heightened deep tendon reflexes. [EU] Specialist: In medicine, one who concentrates on 1 special branch of medical science. [NIH] Species: A taxonomic category subordinate to a genus (or subgenus) and superior to a subspecies or variety, composed of individuals possessing common characters distinguishing them from other categories of individuals of the same taxonomic level. In taxonomic nomenclature, species are designated by the genus name followed by a Latin or Latinized adjective or noun. [EU] Specificity: Degree of selectivity shown by an antibody with respect to the number and types of antigens with which the antibody combines, as well as with respect to the rates and the extents of these reactions. [NIH] Spectrum: A charted band of wavelengths of electromagnetic vibrations obtained by refraction and diffraction. By extension, a measurable range of activity, such as the range of bacteria affected by an antibiotic (antibacterial s.) or the complete range of manifestations of a disease. [EU] Sperm: The fecundating fluid of the male. [NIH] Spermatozoa: Mature male germ cells that develop in the seminiferous tubules of the testes. Each consists of a head, a body, and a tail that provides propulsion. The head consists mainly of chromatin. [NIH] Spermicide: An agent that is destructive to spermatozoa. [EU] Spermidine: A polyamine formed from putrescine. It is found in almost all tissues in association with nucleic acids. It is found as a cation at all pH values, and is thought to help stabilize some membranes and nucleic acid structures. It is a precursor of spermine. [NIH] Spinal cord: The main trunk or bundle of nerves running down the spine through holes in the spinal bone (the vertebrae) from the brain to the level of the lower back. [NIH] Spinous: Like a spine or thorn in shape; having spines. [NIH] Spirochete: Lyme disease. [NIH] Spleen: An organ that is part of the lymphatic system. The spleen produces lymphocytes, filters the blood, stores blood cells, and destroys old blood cells. It is located on the left side of the abdomen near the stomach. [NIH] Sporadic: Neither endemic nor epidemic; occurring occasionally in a random or isolated manner. [EU] Spores: The reproductive elements of lower organisms, such as protozoa, fungi, and cryptogamic plants. [NIH] Stabilization: The creation of a stable state. [EU] Staphylococcus: A genus of gram-positive, facultatively anaerobic, coccoid bacteria. Its

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organisms occur singly, in pairs, and in tetrads and characteristically divide in more than one plane to form irregular clusters. Natural populations of Staphylococcus are membranes of warm-blooded animals. Some species are opportunistic pathogens of humans and animals. [NIH] Staphylococcus aureus: Potentially pathogenic bacteria found in nasal membranes, skin, hair follicles, and perineum of warm-blooded animals. They may cause a wide range of infections and intoxications. [NIH] Stem Cells: Relatively undifferentiated cells of the same lineage (family type) that retain the ability to divide and cycle throughout postnatal life to provide cells that can become specialized and take the place of those that die or are lost. [NIH] Steroid: A group name for lipids that contain a hydrogenated cyclopentanoperhydrophenanthrene ring system. Some of the substances included in this group are progesterone, adrenocortical hormones, the gonadal hormones, cardiac aglycones, bile acids, sterols (such as cholesterol), toad poisons, saponins, and some of the carcinogenic hydrocarbons. [EU] Stimulant: 1. Producing stimulation; especially producing stimulation by causing tension on muscle fibre through the nervous tissue. 2. An agent or remedy that produces stimulation. [EU]

Stimulus: That which can elicit or evoke action (response) in a muscle, nerve, gland or other excitable issue, or cause an augmenting action upon any function or metabolic process. [NIH] Stomach: An organ of digestion situated in the left upper quadrant of the abdomen between the termination of the esophagus and the beginning of the duodenum. [NIH] Stool: The waste matter discharged in a bowel movement; feces. [NIH] Strand: DNA normally exists in the bacterial nucleus in a helix, in which two strands are coiled together. [NIH] Streptavidin: A 60kD extracellular protein of Streptomyces avidinii with four high-affinity biotin binding sites. Unlike AVIDIN, streptavidin has a near neutral isoelectric point and is free of carbohydrate side chains. [NIH] Streptococcal: Caused by infection due to any species of streptococcus. [NIH] Streptococci: A genus of spherical Gram-positive bacteria occurring in chains or pairs. They are widely distributed in nature, being important pathogens but often found as normal commensals in the mouth, skin, and intestine of humans and other animals. [NIH] Streptococcus: A genus of gram-positive, coccoid bacteria whose organisms occur in pairs or chains. No endospores are produced. Many species exist as commensals or parasites on man or animals with some being highly pathogenic. A few species are saprophytes and occur in the natural environment. [NIH] Stress: Forcibly exerted influence; pressure. Any condition or situation that causes strain or tension. Stress may be either physical or psychologic, or both. [NIH] Stroke: Sudden loss of function of part of the brain because of loss of blood flow. Stroke may be caused by a clot (thrombosis) or rupture (hemorrhage) of a blood vessel to the brain. [NIH] Stromal: Large, veil-like cell in the bone marrow. [NIH] Stromal Cells: Connective tissue cells of an organ found in the loose connective tissue. These are most often associated with the uterine mucosa and the ovary as well as the hematopoietic system and elsewhere. [NIH] Styrene: A colorless, toxic liquid with a strong aromatic odor. It is used to make rubbers, polymers and copolymers, and polystyrene plastics. [NIH]

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Subacute: Somewhat acute; between acute and chronic. [EU] Subclinical: Without clinical manifestations; said of the early stage(s) of an infection or other disease or abnormality before symptoms and signs become apparent or detectable by clinical examination or laboratory tests, or of a very mild form of an infection or other disease or abnormality. [EU] Subcutaneous: Beneath the skin. [NIH] Submaxillary: Four to six lymph glands, located between the lower jaw and the submandibular salivary gland. [NIH] Subspecies: A category intermediate in rank between species and variety, based on a smaller number of correlated characters than are used to differentiate species and generally conditioned by geographical and/or ecological occurrence. [NIH] Substance P: An eleven-amino acid neurotransmitter that appears in both the central and peripheral nervous systems. It is involved in transmission of pain, causes rapid contractions of the gastrointestinal smooth muscle, and modulates inflammatory and immune responses. [NIH]

Substrate: A substance upon which an enzyme acts. [EU] Substrate Specificity: A characteristic feature of enzyme activity in relation to the kind of substrate on which the enzyme or catalytic molecule reacts. [NIH] Subtilisin: A serine endopeptidase isolated from Bacillus subtilis. It hydrolyzes proteins with broad specificity for peptide bonds, and a preference for a large uncharged residue in P1. It also hydrolyzes peptide amides. (From Enzyme Nomenclature, 1992) EC 3.4.21.62. [NIH]

Suction: The removal of secretions, gas or fluid from hollow or tubular organs or cavities by means of a tube and a device that acts on negative pressure. [NIH] Sulfadiazine: A short-acting sulfonamide used in combination with pyrimethamine to treat toxoplasmosis in patients with acquired immunodeficiency syndrome and in newborns with congenital infections. [NIH] Sulfates: Inorganic salts of sulfuric acid. [NIH] Sulfur: An element that is a member of the chalcogen family. It has an atomic symbol S, atomic number 16, and atomic weight 32.066. It is found in the amino acids cysteine and methionine. [NIH] Sulfuric acid: A strong acid that, when concentrated is extemely corrosive to the skin and mucous membranes. It is used in making fertilizers, dyes, electroplating, and industrial explosives. [NIH] Superoxide: Derivative of molecular oxygen that can damage cells. [NIH] Superoxide Dismutase: An oxidoreductase that catalyzes the reaction between superoxide anions and hydrogen to yield molecular oxygen and hydrogen peroxide. The enzyme protects the cell against dangerous levels of superoxide. EC 1.15.1.1. [NIH] Supportive care: Treatment given to prevent, control, or relieve complications and side effects and to improve the comfort and quality of life of people who have cancer. [NIH] Suppression: A conscious exclusion of disapproved desire contrary with repression, in which the process of exclusion is not conscious. [NIH] Suppressive: Tending to suppress : effecting suppression; specifically : serving to suppress activity, function, symptoms. [EU] Suppurative: Consisting of, containing, associated with, or identified by the formation of pus. [NIH]

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Surfactant: A fat-containing protein in the respiratory passages which reduces the surface tension of pulmonary fluids and contributes to the elastic properties of pulmonary tissue. [NIH]

Sympathomimetic: 1. Mimicking the effects of impulses conveyed by adrenergic postganglionic fibres of the sympathetic nervous system. 2. An agent that produces effects similar to those of impulses conveyed by adrenergic postganglionic fibres of the sympathetic nervous system. Called also adrenergic. [EU] Symphysis: A secondary cartilaginous joint. [NIH] Symptomatic: Having to do with symptoms, which are signs of a condition or disease. [NIH] Synapses: Specialized junctions at which a neuron communicates with a target cell. At classical synapses, a neuron's presynaptic terminal releases a chemical transmitter stored in synaptic vesicles which diffuses across a narrow synaptic cleft and activates receptors on the postsynaptic membrane of the target cell. The target may be a dendrite, cell body, or axon of another neuron, or a specialized region of a muscle or secretory cell. Neurons may also communicate through direct electrical connections which are sometimes called electrical synapses; these are not included here but rather in gap junctions. [NIH] Synaptic: Pertaining to or affecting a synapse (= site of functional apposition between neurons, at which an impulse is transmitted from one neuron to another by electrical or chemical means); pertaining to synapsis (= pairing off in point-for-point association of homologous chromosomes from the male and female pronuclei during the early prophase of meiosis). [EU] Synergistic: Acting together; enhancing the effect of another force or agent. [EU] Systemic: Affecting the entire body. [NIH] Tachycardia: Excessive rapidity in the action of the heart, usually with a heart rate above 100 beats per minute. [NIH] Tachypnea: Rapid breathing. [NIH] Teichoic Acids: Bacterial polysaccharides that are rich in phosphodiester linkages. They are the major components of the cell walls and membranes of many bacteria. [NIH] Telangiectasia: The permanent enlargement of blood vessels, causing redness in the skin or mucous membranes. [NIH] Temazepam: A benzodiazepinone that acts as a GABA modulator and anti-anxiety agent. [NIH]

Temporal: One of the two irregular bones forming part of the lateral surfaces and base of the skull, and containing the organs of hearing. [NIH] Teratogenic: Tending to produce anomalies of formation, or teratism (= anomaly of formation or development : condition of a monster). [EU] Terminator: A DNA sequence sited at the end of a transcriptional unit that signals the end of transcription. [NIH] Testicular: Pertaining to a testis. [EU] Testosterone: A hormone that promotes the development and maintenance of male sex characteristics. [NIH] Tetracycline: An antibiotic originally produced by Streptomyces viridifaciens, but used mostly in synthetic form. It is an inhibitor of aminoacyl-tRNA binding during protein synthesis. [NIH] Tetracycline Resistance: Nonsusceptibility of a microbe (usually a bacterium) to the action of tetracycline, which binds to the 30S ribosomal subunit and prevents the normal binding

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of aminoacyl-tRNA. [NIH] Thalamic: Cell that reaches the lateral nucleus of amygdala. [NIH] Thalamic Diseases: Disorders of the centrally located thalamus, which integrates a wide range of cortical and subcortical information. Manifestations include sensory loss, movement disorders; ataxia, pain syndromes, visual disorders, a variety of neuropsychological conditions, and coma. Relatively common etiologies include cerebrovascular disorders; craniocerebral trauma; brain neoplasms; brain hypoxia; intracranial hemorrhages; and infectious processes. [NIH] Theophylline: Alkaloid obtained from Thea sinensis (tea) and others. It stimulates the heart and central nervous system, dilates bronchi and blood vessels, and causes diuresis. The drug is used mainly in bronchial asthma and for myocardial stimulation. Among its more prominent cellular effects are inhibition of cyclic nucleotide phosphodiesterases and antagonism of adenosine receptors. [NIH] Therapeutics: The branch of medicine which is concerned with the treatment of diseases, palliative or curative. [NIH] Thermal: Pertaining to or characterized by heat. [EU] Thioredoxin: A hydrogen-carrying protein that participates in a variety of biochemical reactions including ribonucleotide reduction. Thioredoxin is oxidized from a dithiol to a disulfide during ribonucleotide reduction. The disulfide form is then reduced by NADPH in a reaction catalyzed by thioredoxin reductase. [NIH] Thoracic: Having to do with the chest. [NIH] Threonine: An essential amino acid occurring naturally in the L-form, which is the active form. It is found in eggs, milk, gelatin, and other proteins. [NIH] Threshold: For a specified sensory modality (e. g. light, sound, vibration), the lowest level (absolute threshold) or smallest difference (difference threshold, difference limen) or intensity of the stimulus discernible in prescribed conditions of stimulation. [NIH] Thrombin: An enzyme formed from prothrombin that converts fibrinogen to fibrin. (Dorland, 27th ed) EC 3.4.21.5. [NIH] Thrombocytopenia: A decrease in the number of blood platelets. [NIH] Thrombolytic: 1. Dissolving or splitting up a thrombus. 2. A thrombolytic agent. [EU] Thrombomodulin: A cell surface glycoprotein of endothelial cells that binds thrombin and serves as a cofactor in the activation of protein C and its regulation of blood coagulation. [NIH]

Thrombosis: The formation or presence of a blood clot inside a blood vessel. [NIH] Thrombus: An aggregation of blood factors, primarily platelets and fibrin with entrapment of cellular elements, frequently causing vascular obstruction at the point of its formation. Some authorities thus differentiate thrombus formation from simple coagulation or clot formation. [EU] Thymidine: A chemical compound found in DNA. Also used as treatment for mucositis. [NIH]

Thymidylate Synthase: An enzyme of the transferase class that catalyzes the reaction 5,10methylenetetrahydrofolate and dUMP to dihydrofolate and dTMP in the synthesis of thymidine triphosphate. (From Dorland, 27th ed) EC 2.1.1.45. [NIH] Thymus: An organ that is part of the lymphatic system, in which T lymphocytes grow and multiply. The thymus is in the chest behind the breastbone. [NIH] Thyroid: A gland located near the windpipe (trachea) that produces thyroid hormone,

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which helps regulate growth and metabolism. [NIH] Thyroid Gland: A highly vascular endocrine gland consisting of two lobes, one on either side of the trachea, joined by a narrow isthmus; it produces the thyroid hormones which are concerned in regulating the metabolic rate of the body. [NIH] Thyroxine: An amino acid of the thyroid gland which exerts a stimulating effect on thyroid metabolism. [NIH] Tinnitus: Sounds that are perceived in the absence of any external noise source which may take the form of buzzing, ringing, clicking, pulsations, and other noises. Objective tinnitus refers to noises generated from within the ear or adjacent structures that can be heard by other individuals. The term subjective tinnitus is used when the sound is audible only to the affected individual. Tinnitus may occur as a manifestation of cochlear diseases; vestibulocochlear nerve diseases; intracranial hypertension; craniocerebral trauma; and other conditions. [NIH] Tissue: A group or layer of cells that are alike in type and work together to perform a specific function. [NIH] Tissue Culture: Maintaining or growing of tissue, organ primordia, or the whole or part of an organ in vitro so as to preserve its architecture and/or function (Dorland, 28th ed). Tissue culture includes both organ culture and cell culture. [NIH] Tolerance: 1. The ability to endure unusually large doses of a drug or toxin. 2. Acquired drug tolerance; a decreasing response to repeated constant doses of a drug or the need for increasing doses to maintain a constant response. [EU] Tomography: Imaging methods that result in sharp images of objects located on a chosen plane and blurred images located above or below the plane. [NIH] Tonsillitis: Inflammation of the tonsils, especially the palatine tonsils. It is often caused by a bacterium. Tonsillitis may be acute, chronic, or recurrent. [NIH] Tooth Preparation: Procedures carried out with regard to the teeth or tooth structures preparatory to specified dental therapeutic and surgical measures. [NIH] Topical: On the surface of the body. [NIH] Toxic: Having to do with poison or something harmful to the body. Toxic substances usually cause unwanted side effects. [NIH] Toxicity: The quality of being poisonous, especially the degree of virulence of a toxic microbe or of a poison. [EU] Toxicology: The science concerned with the detection, chemical composition, and pharmacologic action of toxic substances or poisons and the treatment and prevention of toxic manifestations. [NIH] Toxins: Specific, characterizable, poisonous chemicals, often proteins, with specific biological properties, including immunogenicity, produced by microbes, higher plants, or animals. [NIH] Toxoplasmosis: The acquired form of infection by Toxoplasma gondii in animals and man. [NIH]

Trace element: Substance or element essential to plant or animal life, but present in extremely small amounts. [NIH] Tracer: A substance (such as a radioisotope) used in imaging procedures. [NIH] Trachea: The cartilaginous and membranous tube descending from the larynx and branching into the right and left main bronchi. [NIH] Transcriptase: An enzyme which catalyses the synthesis of a complementary mRNA

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molecule from a DNA template in the presence of a mixture of the four ribonucleotides (ATP, UTP, GTP and CTP). [NIH] Transcription Factors: Endogenous substances, usually proteins, which are effective in the initiation, stimulation, or termination of the genetic transcription process. [NIH] Transduction: The transfer of genes from one cell to another by means of a viral (in the case of bacteria, a bacteriophage) vector or a vector which is similar to a virus particle (pseudovirion). [NIH] Transfection: The uptake of naked or purified DNA into cells, usually eukaryotic. It is analogous to bacterial transformation. [NIH] Transfer Factor: Factor derived from leukocyte lysates of immune donors which can transfer both local and systemic cellular immunity to nonimmune recipients. [NIH] Transferases: Transferases are enzymes transferring a group, for example, the methyl group or a glycosyl group, from one compound (generally regarded as donor) to another compound (generally regarded as acceptor). The classification is based on the scheme "donor:acceptor group transferase". (Enzyme Nomenclature, 1992) EC 2. [NIH] Transgenes: Genes that are introduced into an organism using gene transfer techniques. [NIH]

Translation: The process whereby the genetic information present in the linear sequence of ribonucleotides in mRNA is converted into a corresponding sequence of amino acids in a protein. It occurs on the ribosome and is unidirectional. [NIH] Translational: The cleavage of signal sequence that directs the passage of the protein through a cell or organelle membrane. [NIH] Translocate: The attachment of a fragment of one chromosome to a non-homologous chromosome. [NIH] Translocation: The movement of material in solution inside the body of the plant. [NIH] Transmitter: A chemical substance which effects the passage of nerve impulses from one cell to the other at the synapse. [NIH] Transplantation: Transference of a tissue or organ, alive or dead, within an individual, between individuals of the same species, or between individuals of different species. [NIH] Trauma: Any injury, wound, or shock, must frequently physical or structural shock, producing a disturbance. [NIH] Trees: Woody, usually tall, perennial higher plants (Angiosperms, Gymnosperms, and some Pterophyta) having usually a main stem and numerous branches. [NIH] Triad: Trivalent. [NIH] Trimethoprim-sulfamethoxazole: An antibiotic drug used to treat infection and prevent pneumocystis carinii pneumonia. [NIH] Trypsin: A serine endopeptidase that is formed from trypsinogen in the pancreas. It is converted into its active form by enteropeptidase in the small intestine. It catalyzes hydrolysis of the carboxyl group of either arginine or lysine. EC 3.4.21.4. [NIH] Trypsin Inhibitors: Serine proteinase inhibitors which inhibit trypsin. They may be endogenous or exogenous compounds. [NIH] Tsh: A glycoprotein secreted by the pars distalis of the pituitary gland in vertebrates that has hormonal activity. It stimulates the growth of the thyroid gland, as well as the secretion of thyroid hormone. [NIH] Tuberculosis: Any of the infectious diseases of man and other animals caused by species of

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Mycobacterium. [NIH] Tuberous Sclerosis: A rare congenital disease in which the essential pathology is the appearance of multiple tumors in the cerebrum and in other organs, such as the heart or kidneys. [NIH] Tumor Necrosis Factor: Serum glycoprotein produced by activated macrophages and other mammalian mononuclear leukocytes which has necrotizing activity against tumor cell lines and increases ability to reject tumor transplants. It mimics the action of endotoxin but differs from it. It has a molecular weight of less than 70,000 kDa. [NIH] Tylosin: Macrolide antibiotic obtained from cultures of Streptomyces fradiae. The drug is effective against many microorganisms in animals but not in humans. [NIH] TYPHI: The bacterium that gives rise to typhoid fever. [NIH] Typhimurium: Microbial assay which measures his-his+ reversion by chemicals which cause base substitutions or frameshift mutations in the genome of this organism. [NIH] Typhoid fever: The most important member of the enteric group of fevers which also includes the paratyphoids. [NIH] Typhoid fever: The most important member of the enteric group of fevers which also includes the paratyphoids. [NIH] Tyrosine: A non-essential amino acid. In animals it is synthesized from phenylalanine. It is also the precursor of epinephrine, thyroid hormones, and melanin. [NIH] Ubiquinone: A lipid-soluble benzoquinone which is involved in electron transport in mitochondrial preparations. The compound occurs in the majority of aerobic organisms, from bacteria to higher plants and animals. [NIH] Ubiquitin: A highly conserved 76 amino acid-protein found in all eukaryotic cells. [NIH] Ulcer: A localized necrotic lesion of the skin or a mucous surface. [NIH] Ulceration: 1. The formation or development of an ulcer. 2. An ulcer. [EU] Ulcerative colitis: Chronic inflammation of the colon that produces ulcers in its lining. This condition is marked by abdominal pain, cramps, and loose discharges of pus, blood, and mucus from the bowel. [NIH] Unconscious: Experience which was once conscious, but was subsequently rejected, as the "personal unconscious". [NIH] Uracil: An anticancer drug that belongs to the family of drugs called alkylating agents. [NIH] Urea: A compound (CO(NH2)2), formed in the liver from ammonia produced by the deamination of amino acids. It is the principal end product of protein catabolism and constitutes about one half of the total urinary solids. [NIH] Uremia: The illness associated with the buildup of urea in the blood because the kidneys are not working effectively. Symptoms include nausea, vomiting, loss of appetite, weakness, and mental confusion. [NIH] Ureters: Tubes that carry urine from the kidneys to the bladder. [NIH] Urethra: The tube through which urine leaves the body. It empties urine from the bladder. [NIH]

Urinary: Having to do with urine or the organs of the body that produce and get rid of urine. [NIH] Urinary tract: The organs of the body that produce and discharge urine. These include the kidneys, ureters, bladder, and urethra. [NIH] Urinary tract infection: An illness caused by harmful bacteria growing in the urinary tract.

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[NIH]

Urine: Fluid containing water and waste products. Urine is made by the kidneys, stored in the bladder, and leaves the body through the urethra. [NIH] Urogenital: Pertaining to the urinary and genital apparatus; genitourinary. [EU] Urokinase: A drug that dissolves blood clots or prevents them from forming. [NIH] Uroporphyrinogen Decarboxylase: One of the enzymes active in heme biosynthesis. It catalyzes the decarboxylation of uroporphyrinogen III to coproporphyrinogen III by the conversion of four acetic acid groups to four methyl groups. EC 4.1.1.37. [NIH] Uterus: The small, hollow, pear-shaped organ in a woman's pelvis. This is the organ in which a fetus develops. Also called the womb. [NIH] Vaccination: Administration of vaccines to stimulate the host's immune response. This includes any preparation intended for active immunological prophylaxis. [NIH] Vaccine: A substance or group of substances meant to cause the immune system to respond to a tumor or to microorganisms, such as bacteria or viruses. [NIH] Vacuoles: Any spaces or cavities within a cell. They may function in digestion, storage, secretion, or excretion. [NIH] Vagina: The muscular canal extending from the uterus to the exterior of the body. Also called the birth canal. [NIH] Vaginal: Of or having to do with the vagina, the birth canal. [NIH] Vancomycin: Antibacterial obtained from Streptomyces orientalis. It is a glycopeptide related to ristocetin that inhibits bacterial cell wall assembly and is toxic to kidneys and the inner ear. [NIH] Vascular: Pertaining to blood vessels or indicative of a copious blood supply. [EU] Vasodilator: An agent that widens blood vessels. [NIH] Vector: Plasmid or other self-replicating DNA molecule that transfers DNA between cells in nature or in recombinant DNA technology. [NIH] Vegetable Proteins: Proteins which are present in or isolated from vegetables or vegetable products used as food. The concept is distinguished from plant proteins which refers to nondietary proteins from plants. [NIH] Vegetative: 1. Concerned with growth and with nutrition. 2. Functioning involuntarily or unconsciously, as the vegetative nervous system. 3. Resting; denoting the portion of a cell cycle during which the cell is not involved in replication. 4. Of, pertaining to, or characteristic of plants. [EU] Vein: Vessel-carrying blood from various parts of the body to the heart. [NIH] Venom: That produced by the poison glands of the mouth and injected by the fangs of poisonous snakes. [NIH] Venous: Of or pertaining to the veins. [EU] Venous blood: Blood that has given up its oxygen to the tissues and carries carbon dioxide back for gas exchange. [NIH] Ventricles: Fluid-filled cavities in the heart or brain. [NIH] Ventricular: Pertaining to a ventricle. [EU] Venules: The minute vessels that collect blood from the capillary plexuses and join together to form veins. [NIH] Vertigo: An illusion of movement; a sensation as if the external world were revolving

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around the patient (objective vertigo) or as if he himself were revolving in space (subjective vertigo). The term is sometimes erroneously used to mean any form of dizziness. [EU] Vesicular: 1. Composed of or relating to small, saclike bodies. 2. Pertaining to or made up of vesicles on the skin. [EU] Vesicular Exanthema of Swine: A calicivirus infection of swine characterized by hydropic degeneration of the oral and cutaneous epithelia. [NIH] Vesicular Exanthema of Swine Virus: The type species of the genus Calicivirus, an RNA virus infecting pigs. The resulting infection is an acute febrile disease which is clinically indistinguishable from foot and mouth disease. Transmission is by contaminated food. [NIH] Veterinary Medicine: The medical science concerned with the prevention, diagnosis, and treatment of diseases in animals. [NIH] Vibrio: A genus of Vibrionaceae, made up of short, slightly curved, motile, gram-negative rods. Various species produce cholera and other gastrointestinal disorders as well as abortion in sheep and cattle. [NIH] Vibrio cholerae: The etiologic agent of cholera. [NIH] Villi: The tiny, fingerlike projections on the surface of the small intestine. Villi help absorb nutrients. [NIH] Vinculin: A cytoskeletal protein associated with cell-cell and cell-matrix interactions. The amino acid sequence of human vinculin has been determined. The protein consists of 1066 amino acid residues and its gene has been assigned to chromosome 10. [NIH] Viral: Pertaining to, caused by, or of the nature of virus. [EU] Viral vector: A type of virus used in cancer therapy. The virus is changed in the laboratory and cannot cause disease. Viral vectors produce tumor antigens (proteins found on a tumor cell) and can stimulate an antitumor immune response in the body. Viral vectors may also be used to carry genes that can change cancer cells back to normal cells. [NIH] Virion: The infective system of a virus, composed of the viral genome, a protein core, and a protein coat called a capsid, which may be naked or enclosed in a lipoprotein envelope called the peplos. [NIH] Virulence: The degree of pathogenicity within a group or species of microorganisms or viruses as indicated by case fatality rates and/or the ability of the organism to invade the tissues of the host. [NIH] Virulent: A virus or bacteriophage capable only of lytic growth, as opposed to temperate phages establishing the lysogenic response. [NIH] Virus: Submicroscopic organism that causes infectious disease. In cancer therapy, some viruses may be made into vaccines that help the body build an immune response to, and kill, tumor cells. [NIH] Vitiligo: A disorder consisting of areas of macular depigmentation, commonly on extensor aspects of extremities, on the face or neck, and in skin folds. Age of onset is often in young adulthood and the condition tends to progress gradually with lesions enlarging and extending until a quiescent state is reached. [NIH] Vitro: Descriptive of an event or enzyme reaction under experimental investigation occurring outside a living organism. Parts of an organism or microorganism are used together with artificial substrates and/or conditions. [NIH] Vivo: Outside of or removed from the body of a living organism. [NIH] Vulgaris: An affection of the skin, especially of the face, the back and the chest, due to chronic inflammation of the sebaceous glands and the hair follicles. [NIH]

372 E. coli

War: Hostile conflict between organized groups of people. [NIH] Warts: Benign epidermal proliferations or tumors; some are viral in origin. [NIH] Weight Gain: Increase in body weight over existing weight. [NIH] White blood cell: A type of cell in the immune system that helps the body fight infection and disease. White blood cells include lymphocytes, granulocytes, macrophages, and others. [NIH]

Windpipe: A rigid tube, 10 cm long, extending from the cricoid cartilage to the upper border of the fifth thoracic vertebra. [NIH] Withdrawal: 1. A pathological retreat from interpersonal contact and social involvement, as may occur in schizophrenia, depression, or schizoid avoidant and schizotypal personality disorders. 2. (DSM III-R) A substance-specific organic brain syndrome that follows the cessation of use or reduction in intake of a psychoactive substance that had been regularly used to induce a state of intoxication. [EU] Wound Healing: Restoration of integrity to traumatized tissue. [NIH] Xanthine: An urinary calculus. [NIH] Xenobiotics: Chemical substances that are foreign to the biological system. They include naturally occurring compounds, drugs, environmental agents, carcinogens, insecticides, etc. [NIH]

Xenograft: The cells of one species transplanted to another species. [NIH] X-ray: High-energy radiation used in low doses to diagnose diseases and in high doses to treat cancer. [NIH] Yeasts: A general term for single-celled rounded fungi that reproduce by budding. Brewers' and bakers' yeasts are Saccharomyces cerevisiae; therapeutic dried yeast is dried yeast. [NIH] Yersinia: A genus of gram-negative, facultatively anaerobic rod- to coccobacillus-shaped bacteria that occurs in a broad spectrum of habitats. [NIH] Yersinia enterocolitica: A species of the genus Yersinia, isolated from both man and animal. It is a frequent cause of bacterial gastroenteritis in children. [NIH] Yersinia pseudotuberculosis: A human and animal pathogen causing mesenteric lymphadenitis, diarrhea, and bacteremia. [NIH] Zygote: The fertilized ovum. [NIH] Zymogen: Inactive form of an enzyme which can then be converted to the active form, usually by excision of a polypeptide, e. g. trypsinogen is the zymogen of trypsin. [NIH]

373

INDEX A Abdomen, 287, 297, 298, 330, 334, 345, 347, 362, 363 Abdominal, 248, 287, 299, 310, 318, 320, 331, 337, 345, 347, 369 Abdominal Pain, 248, 287, 318, 320, 331, 347, 369 Aberrant, 9, 287, 307 Acceptor, 287, 333, 344, 368 Acetylcholine, 287, 342 Acetylgalactosamine, 127, 287 Acquired Immunodeficiency Syndrome, 222, 287, 364 Acremonium, 287, 301 Acrylonitrile, 287, 358 Actin, 4, 23, 118, 143, 231, 287 Acute lymphoblastic leukemia, 105, 128, 131, 140, 145, 287 Acute lymphocytic leukemia, 287 Acute renal, 4, 48, 287, 324 Acyl, 131, 216, 221, 226, 287 Acyl Carrier Protein, 216, 287 Adaptability, 288, 300, 301 Adaptation, 16, 68, 288, 339 Adduct, 9, 288 Adenine, 34, 199, 288, 354 Adenitis, 206, 288 Adenocarcinoma, 154, 159, 288 Adenosine, 27, 34, 38, 41, 288, 294, 299, 326, 348, 366 Adenosine Kinase, 38, 288 Adenosine Triphosphate, 34, 288, 294, 348 Adenosylmethionine Decarboxylase, 62, 288 Adenovirus, 142, 288 Adenylate Cyclase, 288, 303 Adjustment, 288 Adjuvant, 49, 288, 320 Adrenal Medulla, 288, 315, 342 Adrenergic, 56, 144, 288, 312, 315, 365 Adsorption, 65, 141, 222, 288 Adsorptive, 288 Adverse Effect, 288, 360 Aerobic, 65, 68, 119, 289, 307, 338, 340, 344, 369 Aetiology, 227, 289 Affinity, 19, 27, 32, 37, 42, 56, 64, 108, 182, 196, 206, 232, 289, 363

Affinity Chromatography, 27, 196, 232, 289 Agar, 74, 76, 90, 289, 305, 307 Age Groups, 214, 220, 289 Aged, 80 and Over, 289 Agonist, 110, 289, 312 Alanine, 16, 22, 289 Alanine Racemase, 22, 289 Albumin, 7, 227, 289, 349 Alertness, 289, 299 Alfalfa, 111, 289 Algorithms, 181, 289, 297 Alkaline, 150, 155, 290, 291, 299, 347 Alkaline Phosphatase, 150, 155, 290 Alkylating Agents, 61, 290, 369 Alkylation, 61, 86, 104, 185, 290 Allergen, 290, 310, 360 Alpha Particles, 290, 355 Alpha-1, 290, 348 Alpha-helices, 41, 290 Alternative medicine, 252, 290 Amber, 290, 328 Amine, 290, 325 Amino Acid Sequence, 100, 198, 208, 211, 213, 215, 220, 224, 290, 292, 320, 371 Amino Acid Substitution, 68, 209, 290 Aminolevulinic Acid, 204, 290 Aminopeptidases, 41, 291, 316 Amino-terminal, 56, 119, 291 Ammonia, 218, 229, 290, 291, 321, 369 Amniotic Fluid, 291, 336 Amoxicillin, 5, 211, 291 Ampicillin, 67, 291 Amplification, 85, 92, 94, 97, 142, 203, 222, 233, 291 Amylase, 227, 291 Anaerobic, 40, 65, 69, 119, 291, 307, 316, 333, 346, 358, 361, 362, 372 Anaesthesia, 291, 328 Analog, 28, 41, 61, 153, 158, 291, 318 Analogous, 45, 63, 101, 211, 291, 312, 368 Anaphylatoxins, 291, 305 Anatomical, 291, 327, 359 Androgens, 291, 293 Anemia, 7, 245, 267, 291, 304, 323, 324, 335 Angiogenesis, 208, 291, 336 Angiotensinogen, 291, 356 Animal model, 36, 44, 291

374 E. coli

Anionic, 20, 221, 292, 344 Anions, 107, 289, 292, 331, 360, 364 Annealing, 203, 292, 350 Anode, 292 Anorexia, 292, 320 Antagonism, 292, 299, 366 Anthrax, 204, 292 Antibacterial, 11, 16, 46, 69, 99, 155, 186, 194, 232, 292, 342, 362, 370 Anticoagulant, 40, 292, 353 Anticodon, 143, 153, 159, 292 Anticonvulsant, 292, 334 Antifibrinolytic, 40, 292 Antigen, 11, 49, 68, 69, 70, 74, 76, 82, 84, 86, 90, 97, 100, 121, 135, 139, 140, 142, 146, 196, 198, 199, 211, 220, 225, 228, 231, 244, 289, 292, 293, 295, 300, 305, 310, 313, 318, 325, 326, 327, 328, 336, 360 Antigen-Antibody Complex, 292, 305, 318 Antigen-presenting cell, 292, 310 Anti-infective, 293, 326, 331, 342 Anti-inflammatory, 29, 40, 293 Antimetabolite, 293, 316, 318 Antineoplastic, 290, 293, 297, 312, 318, 345 Antineoplastic Agents, 290, 293 Antioxidant, 48, 293, 344, 345 Antiserum, 293, 295 Antithrombotic, 48, 293 Antiviral, 293, 330 Anuria, 293, 332 Anus, 293, 298, 346, 355 Anxiety, 293, 334, 344, 365 Aperture, 212, 293 Apolipoproteins, 293, 334 Apoptosis, 34, 130, 293 Aqueous, 79, 133, 221, 293, 296, 308, 313, 326, 333, 334 Arachidonic Acid, 293, 333 Arginine, 70, 232, 233, 291, 293, 342, 354, 368 Aromatase, 166, 293 Aromatic, 35, 61, 71, 294, 303, 348, 363 Arterial, 294, 301, 303, 326, 353 Arteries, 121, 294, 298, 307, 334, 337 Arterioles, 294, 298, 299 Articular, 91, 294 Ascites, 294, 343 Asparaginase, 105, 124, 128, 131, 140, 145, 294 Aspartate, 153, 158, 229, 294, 321 Asymptomatic, 33, 73, 102, 239, 245, 294 Ataxia, 209, 267, 294, 325, 366

Atopic, 106, 294 Atrophy, 266, 267, 294 Attenuated, 49, 210, 211, 294, 295 Attenuation, 74, 212, 294 Autacoids, 55, 294 Autoantibodies, 141, 294 Autoantigens, 294 Autoimmune disease, 221, 240, 294, 339, 349 Autoimmunity, 136, 294 Autologous, 294, 298, 327 Autologous bone marrow transplantation, 294, 327 Autolysis, 15, 294 Autonomic, 287, 295, 342, 347 Avian, 92, 95, 124, 178, 295 Avidity, 244, 295 B Bacillus, 16, 72, 92, 102, 198, 217, 224, 235, 292, 295, 364 Bacillus cereus, 295 Bacillus subtilis, 16, 72, 92, 102, 198, 295, 364 Bacteremia, 58, 71, 93, 295, 358, 372 Bacteria, 4, 6, 7, 8, 11, 12, 13, 16, 17, 19, 21, 22, 25, 27, 29, 31, 32, 35, 37, 43, 51, 55, 58, 65, 66, 84, 94, 106, 127, 133, 150, 165, 183, 195, 196, 198, 199, 202, 205, 207, 209, 210, 211, 212, 215, 217, 218, 220, 224, 231, 235, 239, 243, 247, 251, 274, 287, 288, 292, 295, 296, 297, 306, 308, 314, 316, 317, 318, 319, 321, 322, 324, 325, 329, 330, 332, 333, 334, 338, 340, 346, 349, 352, 355, 356, 358, 360, 362, 363, 365, 368, 369, 370, 372 Bacterial Infections, 202, 272, 295, 301 Bacterial Physiology, 50, 288, 295 Bacterial Proteins, 200, 295 Bacterial toxin, 59, 295 Bacterial Vaccines, 211, 295 Bactericidal, 13, 36, 57, 111, 164, 214, 295, 316, 342 Bacteriocins, 295 Bacteriolysis, 214, 295 Bacteriophage, 51, 55, 59, 76, 91, 101, 102, 177, 178, 196, 215, 244, 295, 358, 368, 371 Bacteriophage lambda, 51, 55, 295 Bacteriostatic, 295, 315 Bacteriuria, 7, 33, 102, 295 Basal Ganglia, 294, 296, 298 Basal Ganglia Diseases, 294, 296 Base Sequence, 32, 230, 296, 308, 319, 320

Index 375

Basophil, 106, 296 Benzene, 210, 296 Beta-Galactosidase, 143, 234, 296 Beta-Lactamases, 69, 90, 296 Bifidobacterium, 155, 296 Bile, 12, 296, 319, 325, 334, 336, 352, 363 Bile Acids, 296, 363 Bile Acids and Salts, 296 Bile Ducts, 296, 352 Bile Pigments, 296, 336 Bilirubin, 20, 289, 296 Binding Sites, 32, 64, 230, 296, 363 Biochemical reactions, 297, 366 Biogenesis, 11, 66, 96, 101, 297 Biological response modifier, 297, 329 Biological therapy, 297, 323 Bioluminescence, 207, 297 Biomass, 212, 297 Biophysics, 15, 18, 23, 51, 65, 154, 159, 166, 213, 297 Biopolymers, 52, 217, 297 Biopsy, 195, 297 Biopsy specimen, 195, 297 Bioterrorism, 30, 297 Biotin, 150, 154, 156, 159, 297, 363 Bivalent, 49, 297 Bladder, 7, 8, 29, 31, 44, 171, 297, 308, 328, 339, 352, 369, 370 Bleomycin, 207, 297 Bloating, 297, 331 Blood Cell Count, 7, 297, 323 Blood Coagulation, 298, 299, 358, 366 Blood Glucose, 298, 324, 329 Blood Groups, 298, 322 Blood Platelets, 298, 336, 366 Blood pressure, 298, 300, 326, 339 Blood-Brain Barrier, 22, 57, 58, 298 Blot, 199, 298 Body Fluids, 225, 298, 299, 312 Bone Marrow, 103, 287, 294, 296, 298, 305, 322, 327, 335, 336, 339, 361, 363 Bone Marrow Cells, 103, 298, 305, 336 Bone Marrow Purging, 298, 327 Bowel, 111, 171, 226, 298, 311, 314, 329, 330, 332, 347, 363, 369 Bowel Movement, 298, 311, 363 Brachial, 107, 298 Bradykinin, 298, 342, 349 Brain Neoplasms, 298, 325, 366 Branch, 248, 283, 299, 308, 335, 346, 354, 362, 366 Breakdown, 45, 299, 301, 311, 319, 343

Breeding, 209, 299 Broad-spectrum, 291, 299, 301 Bromine, 205, 299 Bronchial, 299, 325, 366 Buccal, 107, 299 Butyric Acid, 299, 316 Bypass, 9, 10, 299 C Caesarean section, 135, 299 Caffeine, 131, 299, 354 Calcium, 133, 154, 159, 226, 299, 303, 305, 336, 353, 361 Calicivirus, 124, 299, 371 Capillary, 14, 165, 298, 299, 370 Capsid, 299, 343, 371 Capsular, 17, 181, 185, 214, 299 Carbohydrate, 44, 109, 228, 234, 299, 321, 322, 333, 346, 351, 363 Carbon Dioxide, 300, 308, 309, 318, 321, 331, 348, 356, 370 Carcinogen, 9, 288, 300, 340 Carcinogenic, 290, 296, 300, 329, 352, 363 Carcinoma, 114, 142, 300 Cardiac, 152, 157, 201, 299, 300, 313, 315, 340, 363 Cardiovascular, 28, 300, 333 Cardiovascular disease, 28, 300 Carotene, 300, 357 Case report, 4, 115, 300 Catabolism, 32, 70, 94, 96, 300, 369 Catalytic Domain, 12, 300 Cations, 300, 331 Causal, 222, 300, 324, 330, 360 Cause of Death, 15, 201, 300 CEA, 112, 150, 153, 154, 155, 158, 159, 300 Cecum, 36, 87, 300, 332 Cell Cycle, 300, 303, 354, 370 Cell Death, 11, 34, 68, 92, 95, 107, 293, 300, 341 Cell Differentiation, 300, 361 Cell Extracts, 154, 159, 301 Cell membrane, 141, 231, 239, 301, 310, 338, 348 Cell proliferation, 208, 301, 361 Cell Respiration, 301, 338, 344, 356 Cell Size, 69, 301 Cell Survival, 301, 323 Cellular metabolism, 27, 301 Cellulitis, 115, 182, 206, 301 Cellulose, 98, 187, 301, 319, 349

376 E. coli

Central Nervous System, 57, 58, 287, 289, 296, 298, 299, 301, 319, 321, 323, 325, 333, 339, 366 Central Nervous System Infections, 301, 323, 325 Centromere, 24, 301 Cephalosporin Resistance, 110, 301 Cephalosporins, 71, 77, 87, 232, 296, 301 Cerebellar, 294, 301, 356 Cerebral, 294, 296, 298, 301, 302, 307, 315, 316, 325, 336, 362 Cerebral Infarction, 301, 326 Cerebral Palsy, 302, 362 Cerebrospinal, 302, 325 Cerebrospinal fluid, 302, 325 Cerebrovascular, 296, 300, 302, 366 Cerebrum, 301, 302, 369 Cervical, 206, 302 Cervix, 302 Chaos, 133, 302 Chemical Warfare, 302, 309 Chemical Warfare Agents, 302, 309 Chemokines, 117, 140, 302 Chemotactic Factors, 302, 305 Chemotaxis, 41, 62, 184, 302 Chemotherapy, 22, 61, 110, 125, 143, 168, 201, 302, 334, 356 Chlorine, 79, 205, 302 Chlorophyll, 302, 308, 314, 319 Chloroplasts, 302, 308 Cholera, 74, 110, 150, 155, 302, 360, 371 Cholera Toxin, 110, 150, 155, 302 Cholesterol, 296, 303, 307, 326, 334, 359, 363 Cholesterol Esters, 303, 334 Chromatin, 293, 303, 315, 362 Chromosomal, 21, 31, 47, 55, 73, 76, 77, 86, 99, 179, 237, 238, 291, 303, 320, 349, 357, 358 Chromosome Segregation, 64, 303 Chronic renal, 303, 350 Chylomicrons, 303, 334 Chymopapain, 303, 345 Chymotrypsin, 303 Ciprofloxacin, 5, 87, 211, 303 CIS, 24, 303, 357 Cisplatin, 114, 303 Citric Acid, 82, 303, 331 Clear cell carcinoma, 303, 310 Cleave, 41, 61, 205, 303 Clinical Medicine, 303, 351

Clinical trial, 7, 47, 189, 190, 211, 263, 304, 306, 353, 355 Clone, 56, 66, 89, 94, 203, 217, 223, 304 Coagulation, 48, 131, 298, 304, 349, 366 Coal, 296, 304 Cobalt, 41, 304 Cod Liver Oil, 304, 313 Codon, 54, 230, 244, 292, 304, 320, 355, 359 Coenzyme, 67, 186, 216, 235, 304 Cofactor, 18, 28, 84, 304, 353, 366 Coliphages, 295, 304 Colitis, 4, 25, 36, 45, 59, 82, 138, 163, 171, 226, 231, 239, 304, 331 Collagen, 304, 317, 318, 320, 336, 349, 352 Collagenous Colitis, 226, 304 Collapse, 15, 299, 304 Colloidal, 289, 304, 313, 347, 360 Colony-Stimulating Factors, 305, 322 Colorectal, 114, 305 Colorectal Cancer, 114, 305 Colostrum, 108, 119, 146, 172, 305 Commensal, 87, 145, 183, 195, 305 Complement, 35, 57, 62, 76, 101, 111, 132, 214, 223, 291, 292, 305, 320, 335, 349, 360 Complementary and alternative medicine, 163, 175, 305 Complementary medicine, 163, 305 Complementation, 66, 73, 306 Complete remission, 306, 356 Computational Biology, 263, 265, 306 Conception, 306, 317 Condoms, 5, 306 Cones, 55, 306, 357 Confusion, 306, 369 Congestion, 306, 315 Conjugated, 296, 306, 308, 318, 340 Conjugation, 45, 306, 318 Connective Tissue, 298, 301, 304, 306, 318, 319, 320, 334, 337, 347, 357, 363 Consciousness, 306, 309, 311 Constipation, 226, 306, 331, 347 Constriction, 306, 331, 358 Consumption, 306, 310, 320, 345 Contamination, 6, 45, 91, 210, 232, 272, 295, 306, 358 Contraindications, ii, 306 Control group, 25, 306 Convulsions, 209, 292, 307 Coordination, 307, 339 Coproporphyrinogen Oxidase, 123, 204, 307 Coronary, 300, 307, 337

Index 377

Coronary heart disease, 300, 307 Coronary Thrombosis, 307, 337 Corpuscle, 307, 315 Cortex, 294, 307, 316, 352, 356 Cortical, 87, 307, 324, 359, 366 Cortisol, 289, 307 Cosmids, 237, 307 Craniocerebral Trauma, 296, 307, 323, 325, 366, 367 Crossing-over, 307, 355 Crowding, 53, 307 Crystallization, 17, 22, 28, 39, 307 Cultural Characteristics, 226, 307 Culture Media, 233, 289, 307 Cultured cell line, 56, 307 Cultured cells, 307, 308 Curative, 308, 366 Cutaneous, 37, 292, 308, 371 Cyanobacteria, 168, 235, 308 Cyclic, 55, 84, 288, 299, 308, 314, 323, 342, 351, 359, 366 Cyclospora, 274, 308 Cystamine, 308 Cysteamine, 216, 308 Cysteine, 27, 28, 123, 302, 303, 308, 311, 321, 364 Cystine, 227, 308, 311 Cystitis, 8, 33, 308 Cytochrome, 117, 204, 218, 294, 308, 344 Cytogenetics, 308, 358 Cytokine, 34, 36, 49, 68, 112, 164, 308, 330 Cytokinesis, 60, 308 Cytoplasm, 41, 59, 198, 213, 293, 301, 303, 308, 309, 315, 322, 339, 352, 357 Cytosine, 18, 309 Cytoskeleton, 23, 309, 338 Cytostatic, 309, 340 Cytotoxic, 133, 198, 201, 309, 327, 361 Cytotoxicity, 20, 201, 303, 309 Cytotoxins, 48, 309 D Dairy Products, 309, 332, 358 Databases, Bibliographic, 263, 309 Daunorubicin, 309, 312 Day Care, 7, 83, 309 De novo, 18, 24, 112, 198, 309 Deamination, 104, 309, 369 Decarboxylation, 288, 307, 309, 321, 325, 354, 370 Decontamination, 210, 309 Defense Mechanisms, 57, 309 Degenerative, 309, 324

Dehydration, 302, 309 Deletion, 14, 55, 87, 131, 293, 309 Dementia, 287, 309 Demethylation, 168, 309 Denaturation, 19, 203, 309, 350 Dendrites, 310, 341 Dendritic, 110, 140, 310, 336 Dendritic cell, 110, 140, 310 Density, 29, 46, 70, 88, 109, 212, 310, 334, 343, 350 Deoxyribonucleic, 235, 310, 357, 358 Deoxyribonucleic acid, 235, 310, 357, 358 Deoxyribonucleotides, 310 Depolarization, 310, 361 Deprivation, 235, 310 Depsipeptide, 216, 310 Dermatitis, 106, 310 DES, 150, 154, 155, 159, 199, 291, 310 Desensitization, 144, 310 Desiccation, 53, 310 Detoxification, 204, 310 Deuterium, 40, 310, 326 Developed Countries, 25, 310 Developing Countries, 15, 33, 34, 220, 310 Diabetes Mellitus, 310, 324 Diagnostic procedure, 193, 252, 310 Diaphragm, 5, 310, 350 Diarrhoea, 4, 107, 139, 145, 146, 195, 244, 310, 320 Diffusion, 103, 311, 329, 342 Digestion, 45, 296, 298, 311, 330, 334, 363, 370 Digestive system, 190, 311 Digestive tract, 165, 311, 361 Dihydrotestosterone, 311, 356 Dihydroxy, 311, 314 Dilatation, 311, 352 Dilation, 298, 311, 325 Dimerization, 42, 311 Diploid, 306, 311, 349 Discrimination, 19, 225, 311 Disinfectant, 205, 311, 316 Dissociation, 19, 63, 150, 156, 289, 311, 331 Dissociative Disorders, 311 Disulfides, 106, 227, 311 Disulphides, 311 Dithiothreitol, 227, 311 Diuresis, 299, 311, 366 Diuretic, 311, 362 Dopamine, 311, 348 Doxorubicin, 20, 312 Drug Design, 17, 22, 39, 256, 257, 312

378 E. coli

Drug Interactions, 256, 312 Drug Resistance, 20, 65, 66, 74, 312 Drug Tolerance, 312, 367 Duct, 312, 358 Duodenum, 296, 303, 312, 345, 363 Dura mater, 312, 337, 345 Dyes, 211, 312, 364 Dysplasia, 267, 312 Dystrophy, 266, 312 E Edema, 36, 312, 330, 340, 343 Effector, 34, 56, 223, 287, 305, 312, 341 Effector cell, 312, 341 Efficacy, 19, 211, 212, 312 Elective, 97, 312 Electrocoagulation, 304, 313 Electrolysis, 292, 300, 313 Electrolyte, 4, 29, 34, 145, 313, 332 Electrons, 293, 296, 313, 331, 344, 355 Electrophoresis, 74, 165, 313 ELISA, 127, 199, 313 Emaciation, 287, 313 Embryo, 300, 313, 328, 337 Emollient, 313, 321 Empirical, 217, 313 Emulsion, 226, 313, 318 Encephalitis, 313, 334 Endemic, 236, 302, 313, 335, 362 Endocarditis, 313, 334 Endocrine System, 313, 341 Endonucleases, 56, 205, 313 Endothelial cell, 11, 14, 22, 40, 41, 48, 57, 144, 208, 298, 314, 318, 366 Endothelium, 36, 314, 342, 349 Endothelium, Lymphatic, 314 Endothelium, Vascular, 314 Endothelium-derived, 314, 342 Endotoxin, 11, 73, 106, 112, 164, 314, 369 End-stage renal, 303, 314, 350 Enhancer, 314, 357 Enteric bacteria, 11, 32, 314 Enteric Nervous System, 45, 314 Enteritis, 25, 129, 185, 314 Enterobactin, 26, 314 Enterocolitis, 93, 133, 136, 314 Enterocytes, 4, 209, 314 Enteropeptidase, 314, 368 Enterotoxins, 209, 236, 314 Environmental Exposure, 314, 343 Environmental Health, 115, 128, 262, 264, 314

Enzymatic, 11, 16, 26, 27, 39, 53, 57, 61, 62, 66, 81, 199, 204, 231, 232, 299, 300, 305, 314, 317, 318, 325, 345, 350, 357 Eosinophils, 315, 322, 333 Epidemic, 236, 315, 362 Epidemiological, 4, 33, 79, 89, 132, 315 Epidermal, 105, 201, 315, 332, 336, 372 Epidermal Growth Factor, 105, 201, 315 Epidermis, 315, 331, 332, 352, 354 Epinephrine, 288, 312, 315, 342, 369 Epithelial, 4, 8, 26, 29, 34, 36, 44, 47, 87, 104, 107, 108, 122, 126, 133, 150, 155, 167, 237, 288, 303, 315, 322, 324, 345 Epithelium, 26, 34, 195, 314, 315, 345 Epitope, 113, 124, 130, 315 Erysipelas, 206, 315 Erythema, 201, 315 Erythrocyte Indices, 298, 315 Erythrocyte Membrane, 20, 315, 322 Erythrocytes, 291, 297, 298, 315, 324, 355, 360 Erythromycin, 12, 43, 46, 315 Esophagus, 311, 316, 363 Essential Tremor, 267, 316 Estrogen, 33, 293, 316 Ethanol, 70, 78, 82, 316, 317 Ethionine, 62, 316 Eukaryotic Cells, 60, 217, 316, 328, 343, 344, 369 Evacuation, 306, 316, 332 Evoke, 316, 363 Excipient, 220, 316 Excrete, 293, 316, 332, 356 Exfoliation, 44, 316 Exhaustion, 292, 316, 335 Exogenous, 14, 20, 25, 43, 214, 288, 316, 323, 347, 368 Exonucleases, 48, 178, 316 Exopeptidases, 291, 316, 346 Exoribonucleases, 61, 316 Expiration, 316, 356 Extracellular, 18, 82, 97, 306, 316, 317, 318, 336, 363 Extracellular Matrix, 306, 317, 318, 336 Extracellular Matrix Proteins, 317, 336 Extraction, 232, 235, 317 Extrarenal, 189, 317 Extremity, 231, 317 Eye Infections, 288, 317 F Faecal, 109, 310, 317 Family Planning, 263, 317

Index 379

Fat, 293, 296, 298, 299, 300, 305, 307, 317, 333, 339, 351, 357, 358, 361, 365 Fatigue, 274, 317, 323 Fatty acids, 11, 289, 317, 321, 334, 336 Feces, 74, 88, 226, 296, 306, 317, 334, 363 Fermentation, 43, 46, 65, 78, 81, 111, 164, 229, 232, 233, 234, 235, 317, 358, 361 Ferrochelatase, 204, 317 Fetus, 13, 317, 336, 348, 370 Fibrin, 298, 317, 347, 349, 366 Fibrinogen, 133, 317, 349, 366 Fibrinolysis, 292, 317 Fibrinolytic, 40, 317 Fibroblast Growth Factor, 132, 208, 318 Fibroblasts, 165, 318 Fibronectin, 99, 116, 130, 170, 318 Fibrosis, 34, 267, 318, 359 Filtration, 135, 205, 318, 332 Fixation, 318, 360 Flatus, 318, 319 Fluorescence, 24, 41, 43, 107, 130, 152, 157, 184, 196, 318 Fluorescent Antibody Technique, 136, 318 Fluorouracil, 114, 318 Fold, 28, 43, 46, 90, 201, 203, 211, 216, 318, 337 Follicles, 318, 329 Food Handling, 248, 318 Foodborne Illness, 274, 275, 318 Frameshift, 21, 319, 369 Frameshift Mutation, 21, 319, 369 Fructose, 228, 319, 322 Fungi, 22, 51, 218, 297, 306, 317, 319, 330, 338, 362, 372 Fungus, 301, 319 G GABA, 319, 321, 361, 365 Galactosides, 66, 296, 319 Gallbladder, 287, 296, 311, 319 Gamma Rays, 319, 340 Ganglia, 287, 296, 314, 319, 341, 347 Gangrenous, 319, 360 Gas, 130, 135, 291, 300, 302, 311, 318, 319, 326, 331, 340, 342, 364, 370 Gas Gangrene, 130, 319 Gasoline, 210, 296, 319 Gastric, 291, 315, 319, 325, 346 Gastric Acid, 291, 319 Gastrin, 319, 325 Gastroenteritis, 6, 104, 105, 183, 245, 299, 320, 358, 372

Gastrointestinal, 3, 45, 49, 141, 223, 226, 298, 303, 315, 316, 318, 320, 333, 336, 342, 364, 371 Gastrointestinal tract, 45, 226, 316, 320, 333 Gelatin, 307, 320, 321, 366 Gene Expression, 14, 24, 29, 31, 58, 61, 63, 79, 82, 95, 180, 182, 195, 197, 203, 242, 243, 267, 320 Gene Fusion, 51, 320 Gene Library, 320 Genetic Code, 181, 320, 342 Genetic Engineering, 182, 200, 221, 297, 304, 320 Genetic Techniques, 12, 320 Genetic testing, 320, 350 Genetic Vectors, 307, 320 Genital, 303, 320, 370 Genitourinary, 320, 370 Genomic Library, 29, 135, 320 Genomics, 17, 21, 32, 320 Genotype, 81, 83, 321, 348 Germ Cells, 321, 336, 343, 362 Germ-free, 32, 321 Gland, 68, 288, 321, 334, 336, 345, 348, 352, 359, 363, 364, 366, 367 Glomerular, 37, 321, 332, 356 Glomeruli, 321, 354 Glomerulonephritis, 206, 321, 326 Glucuronic Acid, 321, 324 Glutamate, 70, 72, 83, 151, 156, 321 Glutamate Decarboxylase, 83, 151, 156, 321 Glutamic Acid, 321, 352 Glutamine, 74, 198, 321 Glutathione Peroxidase, 321, 359 Glycerol, 28, 93, 182, 299, 321, 348 Glycerophospholipids, 321, 348 Glycine, 90, 91, 112, 290, 296, 321, 360 Glycogen, 321, 348 Glycophorin, 127, 322 Glycoprotein, 20, 109, 317, 318, 322, 366, 368, 369 Glycoside, 322, 326, 358 Glycosidic, 322, 343, 348 Goblet Cells, 314, 322 Gonadal, 322, 363 Governing Board, 322, 351 Gp120, 17, 322 GP41, 225, 322 Graft, 221, 322, 325, 327, 354 Graft Rejection, 322, 327

380 E. coli

Graft-versus-host disease, 322, 354 Gram-negative, 11, 13, 17, 22, 25, 37, 50, 58, 308, 316, 322, 340, 342, 358, 371, 372 Gram-Negative Bacteria, 11, 13, 308, 322, 340 Gram-positive, 8, 16, 295, 296, 322, 332, 333, 334, 340, 342, 346, 362, 363 Gram-Positive Bacteria, 295, 322 Granule, 322, 357 Granulocyte Colony-Stimulating Factor, 124, 305, 322 Granulocytes, 133, 296, 305, 322, 361, 372 Granulosa Cells, 323, 329 Growth factors, 208, 323 Growth Inhibitors, 211, 323 Guanylate Cyclase, 323, 342 Gyrase, 16, 26, 68, 323, 342 H Habitat, 323, 340 Hair follicles, 323, 363, 371 Handwashing, 7, 323 Haploid, 323, 349 Haptens, 289, 323 Headache, 299, 323, 325, 329 Heart attack, 300, 323 Heart failure, 323, 343 Hematocrit, 298, 315, 323 Hematogenous, 22, 57, 323 Heme, 19, 37, 79, 95, 101, 102, 203, 204, 291, 296, 307, 308, 317, 323, 340, 351, 370 Hemin, 19, 323 Hemodialysis, 323, 332 Hemoglobin, 19, 73, 79, 81, 102, 291, 298, 315, 323, 324, 333, 351 Hemoglobinuria, 266, 324 Hemolysis, 315, 324 Hemolytic-Uremic Syndrome, 4, 73, 79, 89, 90, 98, 116, 241, 324 Hemorrhage, 25, 307, 313, 323, 324, 354, 363 Heparin, 208, 324 Hepatic, 289, 324, 351 Hepatitis, 110, 117, 118, 121, 204, 274, 324 Hepatocytes, 324 Herbicide, 211, 324 Hereditary, 203, 324, 357 Heredity, 320, 324 Herpes, 66, 324 Herpes virus, 66, 324 Herpes Zoster, 324 Heterodimers, 240, 324 Heterogeneity, 102, 289, 324

Heterotrophic, 319, 324 Histamine, 106, 291, 325 Histidine, 41, 42, 222, 325 Homeostasis, 82, 100, 145, 325 Homogenate, 141, 325 Homogeneous, 56, 325 Homologous, 16, 17, 23, 24, 38, 52, 56, 99, 120, 202, 297, 307, 325, 340, 359, 360, 365, 368 Homotypic, 51, 325 Hormonal, 294, 325, 368 Horseradish Peroxidase, 13, 325 Human growth hormone, 106, 117, 325 Human papillomavirus, 132, 325 Humoral, 49, 322, 325 Humour, 325 Hybrid, 12, 51, 64, 92, 104, 229, 304, 325 Hybridization, 29, 120, 124, 222, 325 Hydration, 7, 325 Hydrocephalus, 133, 325, 330 Hydrogel, 111, 326 Hydrogen Peroxide, 78, 83, 95, 232, 321, 326, 333, 364 Hydrolases, 16, 78, 166, 326, 348 Hydrophilic, 326 Hydrophobic, 15, 42, 225, 321, 326, 333 Hydroxylation, 152, 157, 326 Hypercholesterolemia, 326, 346 Hypersensitivity, 84, 99, 124, 211, 290, 310, 326, 333, 357, 360 Hypertension, 300, 326, 330 Hypnotic, 326, 334 Hypotension, 307, 326 Hypoxanthine, 38, 326 I Id, 160, 170, 273, 275, 282, 284, 326 Idiopathic, 226, 326 Ileum, 300, 326 Imidazole, 297, 325, 326 Immune Complex Diseases, 292, 326, 349 Immune function, 31, 326 Immune Sera, 327 Immune-response, 49, 327 Immunity, 4, 29, 110, 126, 132, 136, 141, 223, 287, 289, 309, 327, 330, 368 Immunization, 35, 36, 210, 211, 240, 327, 360 Immunoassay, 76, 110, 143, 327 Immunocompromised, 13, 327 Immunodeficiency, 222, 225, 266, 287, 327 Immunodeficiency syndrome, 327 Immunofluorescence, 39, 327

Index 381

Immunogenic, 49, 200, 327 Immunoglobulin, 36, 132, 144, 240, 292, 318, 327, 339 Immunologic, 298, 302, 326, 327 Immunology, 47, 108, 120, 124, 126, 135, 140, 143, 146, 167, 168, 169, 223, 288, 289, 325, 327 Immunomagnetic Separation, 127, 184, 327 Immunosuppressant, 290, 318, 327 Immunosuppressive, 206, 327 Immunosuppressive therapy, 327 Immunotherapy, 240, 297, 310, 327 Impairment, 28, 57, 76, 294, 317, 327, 337 Impetigo, 206, 328 In situ, 16, 32, 128, 130, 328 In Situ Hybridization, 94, 130, 328 Incision, 299, 328, 330 Incontinence, 325, 328 Incubated, 7, 328 Incubation, 212, 234, 328 Incubation period, 212, 328 Indicative, 242, 328, 346, 370 Induction, 9, 32, 58, 98, 187, 291, 328 Induction therapy, 328 Infancy, 328 Infant, Newborn, 289, 328 Infantile, 67, 107, 129, 136, 146, 237, 244, 328 Infarction, 301, 307, 328, 337 Infectious Bursal Disease Virus, 223, 328 Infectious Diarrhea, 29, 329 Infiltration, 321, 329 Inflammatory bowel disease, 226, 329 Influenza, 322, 329 Ingestion, 36, 292, 329, 350 Inhalation, 329, 350 Inhibin, 113, 329 Initiation, 21, 26, 55, 63, 182, 230, 329, 352, 361, 368 Initiator, 77, 208, 329, 330 Inner ear, 329, 370 Inorganic, 204, 205, 303, 311, 329, 339, 364 Insecticides, 329, 372 Insertional, 39, 219, 329 Insight, 8, 52, 57, 63, 73, 209, 329 Insomnia, 329, 344 Insulator, 329, 339 Insulin, 144, 221, 329 Insulin-dependent diabetes mellitus, 221, 329

Interferon, 14, 36, 122, 135, 140, 329, 330, 335 Interferon-alpha, 135, 330 Interleukin-1, 36, 73, 123, 126, 221, 330 Interleukin-12, 36, 330 Interleukin-2, 330 Intermittent, 203, 204, 330 Interstitial, 330, 356 Intervention Studies, 36, 330 Intestinal, 4, 19, 25, 32, 33, 34, 36, 47, 58, 59, 126, 143, 146, 167, 185, 195, 209, 211, 226, 231, 236, 237, 300, 303, 314, 330, 332, 335, 336, 345 Intestinal Flora, 59, 330 Intracellular Membranes, 330, 337 Intracranial Hemorrhages, 325, 330, 366 Intracranial Hypertension, 323, 325, 330, 367 Intravenous, 132, 330 Intrinsic, 31, 63, 107, 289, 330 Introns, 24, 320, 330 Invasive, 23, 68, 87, 88, 104, 111, 115, 126, 132, 167, 209, 327, 330 Involuntary, 296, 316, 330, 340, 361 Iodine, 205, 330 Ion Channels, 331, 341 Ion Exchange, 301, 331 Ionization, 205, 331 Ionizing, 56, 61, 109, 290, 314, 331 Ions, 42, 186, 296, 311, 313, 317, 326, 331, 339, 353 Irrigation, 111, 331 Irritable Bowel Syndrome, 226, 331 Ischemia, 294, 331 Ischemic Colitis, 121, 331 Isocitrate Dehydrogenase, 80, 331 Isoelectric, 331, 363 Isoelectric Point, 331, 363 J Joint, 294, 303, 331, 365 K Kb, 55, 262, 331 Keratin, 331, 332 Keratinocytes, 165, 332 Kidney Disease, 189, 190, 262, 267, 275, 332 Kidney Failure, 231, 247, 248, 314, 332 Kidney Failure, Acute, 332 Kidney Failure, Chronic, 332 Kinetic, 10, 18, 20, 23, 38, 40, 41, 52, 115, 128, 152, 157, 187, 331, 332, 347 Kluyveromyces, 155, 332

382 E. coli

L Labile, 35, 49, 85, 110, 113, 150, 155, 178, 305, 332 Lactation, 305, 332 Lactobacillus, 33, 167, 168, 332 Lactobacillus acidophilus, 332 Lactobacillus casei, 332 Large Intestine, 32, 97, 231, 236, 300, 305, 311, 330, 332, 355, 361 Latent, 332, 351 Laxative, 289, 332, 362 Lectin, 146, 151, 156, 333, 337, 338 Lens, 299, 333, 356 Leprosy, 139, 199, 333 Lesion, 10, 56, 87, 201, 333, 334, 360, 369 Lethal, 56, 209, 239, 244, 295, 333, 340 Lethargy, 325, 333 Leucine, 42, 187, 333, 346 Leuconostoc, 333 Leukemia, 54, 105, 131, 145, 221, 222, 266, 312, 333 Leukocytes, 107, 297, 298, 302, 315, 322, 330, 333, 339, 369 Leukotrienes, 20, 293, 333 Library Services, 282, 333 Life cycle, 319, 333 Ligament, 333, 352 Ligands, 19, 333 Ligase, 154, 159, 333 Ligation, 166, 333 Linkage, 12, 23, 31, 209, 216, 333 Lipid, 11, 48, 86, 121, 293, 321, 329, 333, 334, 339, 345, 369 Lipid Peroxidation, 48, 333, 345 Lipopolysaccharide, 11, 48, 50, 91, 93, 126, 152, 157, 165, 195, 295, 322, 333 Lipoprotein, 84, 200, 322, 333, 334, 371 Liposome, 24, 334 Lipoxygenase, 333, 334 Lisofylline, 126, 334 Listeria monocytogenes, 164, 165, 334 Liver Neoplasms, 316, 334 Lobe, 301, 325, 334 Localization, 66, 71, 95, 130, 131, 334 Localized, 56, 67, 130, 318, 328, 334, 343, 349, 369 Locomotion, 334, 349 Loop, 54, 113, 334 Lorazepam, 110, 334 Low-density lipoprotein, 334 Luciferase, 207, 334 Lumen, 34, 314, 334

Lymph, 58, 302, 307, 314, 325, 334, 335, 337, 364 Lymph node, 58, 302, 334, 335, 337 Lymphangitis, 206, 335 Lymphatic, 314, 328, 334, 335, 337, 343, 361, 362, 366 Lymphatic system, 334, 335, 361, 362, 366 Lymphoblastic, 335 Lymphoblasts, 287, 335 Lymphocyte, 287, 292, 335, 336 Lymphocyte Count, 287, 335 Lymphoid, 292, 327, 335 Lymphoma, 266, 335 Lysine, 180, 213, 229, 335, 368 Lysophospholipase, 103, 180, 335 Lysosome, 226, 335 Lytic, 59, 208, 295, 335, 360, 371 M Macrolides, 43, 335 Macrophage, 305, 330, 335 Major Histocompatibility Complex, 182, 240, 335 Malabsorption, 266, 335 Malaria, 39, 335, 336 Malaria, Falciparum, 335, 336 Malaria, Vivax, 335, 336 Malate Dehydrogenase, 82, 95, 336 Malignant, 266, 287, 288, 293, 299, 336, 341 Malnutrition, 289, 294, 336, 340 Mammary, 68, 305, 336 Mastitis, 134, 168, 180, 336, 360 Mastoiditis, 206, 336 Matrix metalloproteinase, 115, 120, 336 Meat, 4, 7, 36, 85, 247, 274, 336, 358 Meconium, 134, 336 Mediate, 8, 12, 14, 29, 44, 47, 57, 312, 336 Mediator, 141, 330, 336 MEDLINE, 4, 263, 265, 267, 336 Megakaryocytes, 298, 336 Meiosis, 297, 303, 336, 340, 365 Melanin, 336, 348, 369 Melanocytes, 336 Melanoma, 125, 266, 336 Membrane Proteins, 8, 68, 116, 136, 196, 337, 353, 361 Meninges, 22, 301, 307, 312, 337 Meningitis, 17, 22, 57, 58, 99, 133, 171, 206, 214, 237, 334, 337 Menopause, 337, 351 Mental Disorders, 191, 337 Mental Health, iv, 7, 191, 262, 264, 337, 354

Index 383

Mental Processes, 311, 337, 354 Mental Retardation, 57, 268, 337 Mesenchymal, 315, 337 Mesenteric, 58, 337, 372 Mesenteric Lymphadenitis, 337, 372 Mesentery, 337, 347 Mesocolon, 209, 337 Mesoderm, 208, 337 Meta-Analysis, 139, 337 Metabolite, 12, 218, 337, 352 Metaphase, 130, 297, 337 Metastasis, 208, 336, 337 Methionine, 27, 41, 183, 184, 208, 288, 316, 337, 364 Methyltransferase, 62, 181, 205, 337 MI, 98, 153, 158, 216, 285, 337 Microbe, 242, 248, 337, 365, 367 Microbiological, 90, 98, 139, 212, 229, 236, 274, 338 Microorganism, 196, 207, 213, 226, 229, 232, 233, 234, 238, 304, 338, 345, 371 Micro-organism, 215, 323, 338, 360 Microscopy, 39, 44, 184, 318, 325, 338, 343 Microspheres, 327, 338 Microtubules, 338, 345 Microvilli, 4, 338 Migrans, 201, 338 Milligram, 38, 240, 338 Mistletoe lectin, 112, 164, 338 Mitochondria, 23, 204, 331, 338, 344 Mitochondrial Swelling, 338, 341 Mitosis, 293, 303, 338 Mitotic, 24, 338 Mobility, 62, 110, 338 Modeling, 9, 63, 73, 154, 159, 312, 338, 353 Modification, 10, 12, 27, 38, 49, 91, 153, 158, 184, 198, 232, 320, 338, 355 Modulator, 338, 365 Molecular mass, 338, 361 Molecular Structure, 27, 339 Monitor, 41, 76, 110, 121, 339, 342 Monoclonal, 17, 93, 124, 130, 138, 180, 194, 200, 257, 327, 339 Monoclonal antibodies, 93, 138, 194, 200, 339 Monocytes, 36, 133, 330, 333, 339 Mononuclear, 132, 339, 369 Morphological, 133, 209, 313, 319, 336, 339 Morphology, 60, 69, 70, 92, 224, 339 Motion Sickness, 339, 340 Motor Activity, 307, 339 Mucilaginous, 336, 339

Mucins, 314, 322, 339, 358 Mucosa, 25, 34, 88, 111, 223, 236, 314, 329, 339, 363 Mucosal Ulceration, 25, 339 Mucus, 32, 339, 369 Multidrug resistance, 20, 339 Multiple Organ Failure, 11, 339 Multiple sclerosis, 221, 339 Multivalent, 49, 151, 156, 295, 340 Muscle Fibers, 340 Muscular Atrophy, 266, 340 Muscular Dystrophies, 312, 340 Mustard Gas, 204, 340 Mutagen, 9, 340 Mutagenic, 9, 10, 57, 119, 238, 290, 340 Mutagenicity, 56, 67, 340 Mycobacterial disease, 199, 340 Mycobacterium, 15, 22, 55, 88, 98, 199, 223, 333, 340, 369 Myelin, 339, 340 Myocardium, 337, 340 Myoglobin, 19, 340, 351 Myotonic Dystrophy, 266, 340 N Nalidixic Acid, 5, 340 Natural killer cells, 330, 340 Natural selection, 297, 340 Nausea, 274, 308, 320, 340, 369 NCI, 1, 190, 261, 303, 340 Necrosis, 34, 293, 301, 324, 328, 337, 341 Neonatal, 22, 57, 58, 72, 107, 118, 133, 134, 168, 341 Neonatal period, 22, 341 Neoplasia, 266, 341 Neoplasm, 341 Neoplastic, 61, 335, 341 Nephropathy, 332, 341 Nerve, 98, 187, 288, 294, 307, 310, 314, 336, 339, 341, 345, 351, 357, 359, 363, 367, 368 Nervous System, 267, 301, 321, 336, 341, 347, 365, 370 Networks, 165, 341 Neural, 165, 181, 325, 341 Neuroendocrine, 45, 341 Neurologic, 325, 341 Neuronal, 131, 341, 347 Neurons, 310, 319, 341, 365 Neuropeptide, 129, 341 Neurotoxic, 341 Neurotoxins, 228, 341 Neurotransmitters, 55, 62, 341 Neutrons, 290, 342, 355

384 E. coli

Neutrophil, 14, 25, 26, 40, 68, 342 Neutrophil Infiltration, 25, 342 Nitric Oxide, 94, 133, 186, 342 Nitrofurantoin, 169, 342 Nitrogen, 96, 100, 235, 290, 291, 308, 317, 318, 321, 332, 338, 342 Norepinephrine, 45, 288, 312, 342 Norfloxacin, 5, 342 Nosocomial, 72, 134, 202, 206, 342 Nuclear, 14, 42, 128, 296, 304, 306, 313, 316, 319, 341, 342, 352 Nuclei, 290, 306, 313, 320, 330, 338, 342, 353 Nucleic Acid Hybridization, 325, 342 Nucleocapsid, 110, 343 Nucleolus, 343, 357 Nucleotidases, 326, 343 Nucleus, 293, 296, 303, 308, 310, 315, 316, 319, 336, 339, 342, 343, 352, 353, 363, 366 Nurseries, 109, 343 O Occult, 126, 343 Odour, 294, 343 Oedema, 209, 343 Oligosaccharides, 216, 343 Oliguria, 332, 343 Oncogene, 266, 343 On-line, 110, 285, 343 Oocytes, 39, 343 Opacity, 310, 343 Open Reading Frames, 19, 55, 211, 237, 243, 343 Operon, 9, 30, 55, 59, 78, 81, 85, 99, 100, 179, 184, 229, 343, 352, 356 Opportunistic Infections, 22, 38, 287, 343 Opsin, 343, 357 Orderly, 303, 343 Organ Culture, 343, 367 Organelles, 8, 308, 336, 339, 344, 349 Osmolality, 53, 344 Osmoles, 344 Osmosis, 205, 344 Osmotic, 53, 94, 289, 338, 344, 360 Otitis, 206, 344 Otitis Media, 206, 344 Ovaries, 151, 156, 293, 344 Overexpress, 17, 344 Oxaloacetate, 336, 344 Oxazepam, 110, 344 Oxidants, 35, 344 Oxidation, 40, 152, 158, 287, 293, 308, 311, 321, 333, 344, 345

Oxidation-Reduction, 344 Oxidative metabolism, 333, 344 Oxidative Phosphorylation, 15, 204, 344 Oxidative Stress, 35, 75, 186, 239, 345 Oxygen Consumption, 345, 356 P Pachymeningitis, 337, 345 Paclitaxel, 197, 345 Palliative, 345, 366 Pancreas, 287, 297, 303, 311, 329, 345, 359, 368 Pancreatic, 266, 303, 345 Pancreatic cancer, 266, 345 Pancreatic Juice, 303, 345 Paneth Cells, 314, 345 Papain, 345 Papillomavirus, 345 Paralysis, 209, 345, 362 Parasite, 38, 146, 345 Parasitic, 38, 345 Parasitic Diseases, 38, 345 Paratyphoid Fever, 345, 358 Paroxysmal, 266, 345 Partial remission, 345, 356 Particle, 70, 334, 345, 368 Patch, 41, 345 Pathogen, 3, 6, 8, 13, 17, 25, 29, 36, 45, 53, 136, 147, 234, 236, 239, 241, 328, 345, 372 Pathogenesis, 4, 8, 16, 22, 25, 33, 35, 44, 46, 49, 51, 57, 92, 133, 135, 195, 234, 236, 346 Pathologic, 36, 293, 297, 307, 326, 346, 354, 356 Pathologic Processes, 293, 346 Pathologies, 35, 199, 346 Pathophysiology, 4, 22, 30, 57, 226, 346 Patient Education, 274, 280, 282, 285, 346 Pectins, 346 Pediococcus, 346 Pelvic, 346, 352 Penicillin, 60, 69, 74, 75, 76, 87, 92, 202, 212, 291, 292, 346 Penis, 306, 346 Pepsin, 346 Pepsin A, 346 Peptide, 12, 16, 26, 42, 45, 51, 54, 86, 88, 100, 140, 197, 206, 213, 214, 216, 221, 225, 240, 302, 314, 316, 318, 326, 331, 346, 350, 353, 360, 364 Peptide Elongation Factors, 346, 360 Peptide Hydrolases, 316, 326, 346 Perforation, 293, 346 Pericarditis, 134, 346

Index 385

Pericardium, 346 Perineum, 346, 363 Peripheral blood, 112, 330, 346 Peripheral Nerves, 333, 347 Peripheral Nervous System, 347, 364 Periplasm, 60, 91, 198, 213, 347 Peritoneal, 294, 343, 347 Peritoneal Cavity, 294, 343, 347 Peritoneum, 337, 347 Peritonitis, 75, 130, 138, 142, 347 Peroxide, 53, 347 Petrolatum, 313, 347 Petroleum, 319, 347 PH, 347 Phagocyte, 344, 347 Phagocytosis, 126, 183, 347 Pharmacokinetics, 312, 347 Pharmacologic, 294, 298, 347, 367 Pharyngitis, 206, 347, 359 Phenolphthalein, 313, 347 Phenotype, 55, 70, 99, 126, 217, 306, 347 Phenylalanine, 218, 346, 348, 369 Phosphogluconate Dehydrogenase, 238, 239, 348 Phospholipases, 348, 361 Phospholipids, 225, 317, 334, 348 Phosphoric Monoester Hydrolases, 326, 348 Phosphorus, 154, 159, 243, 299, 348 Phosphorylase, 107, 125, 348 Phosphorylated, 17, 304, 348 Phosphorylation, 4, 41, 50, 108, 144, 153, 158, 208, 348 Photocoagulation, 304, 348 Photoreceptors, 306, 348 Phylogeny, 100, 146, 348 Physiologic, 34, 195, 289, 297, 348, 355, 356 Physiology, 65, 138, 141, 143, 152, 157, 184, 213, 348 Pigment, 224, 296, 302, 336, 340, 348 Pituitary Gland, 318, 348, 368 Placenta, 293, 348, 352 Plant Diseases, 314, 348 Plant Growth Regulators, 323, 349 Plant Proteins, 227, 349, 370 Plasma cells, 292, 349 Plasma Exchange, 247, 349 Plasma protein, 289, 314, 349, 353, 360 Plasmin, 349 Plasminogen, 122, 349 Plasminogen Activators, 349 Plastids, 344, 349

Platelet Activation, 349, 361 Platelet Aggregation, 225, 291, 342, 349 Platelet Count, 7, 349 Platelets, 342, 349, 350, 366 Platinum, 303, 334, 350 Pleated, 240, 332, 350 Pleural, 343, 350 Pleural cavity, 343, 350 Pneumonitis, 206, 350 Poisoning, 171, 248, 272, 273, 274, 295, 318, 320, 340, 350, 358 Polycystic, 267, 350 Polyesters, 217, 350 Polyethylene, 124, 350 Polymerase Chain Reaction, 184, 203, 219, 223, 350 Polymers, 217, 235, 297, 350, 353, 363 Polymorphic, 94, 203, 238, 239, 350 Polymorphism, 66, 77, 105, 182, 350 Polyposis, 305, 351 Polysaccharide, 12, 16, 91, 125, 181, 292, 301, 351, 353 Polyunsaturated fat, 226, 351 Population Dynamics, 65, 351 Porphyria, 203, 204, 351 Porphyrins, 351 Posterior, 294, 337, 345, 351 Postmenopausal, 33, 351 Postnatal, 144, 351, 363 Postoperative, 339, 351 Postsynaptic, 351, 361, 365 Post-translational, 184, 217, 351 Potentiates, 330, 351 Potentiation, 351, 361 Practice Guidelines, 264, 351 Precipitation, 196, 351 Precursor, 26, 43, 46, 198, 218, 291, 293, 312, 314, 322, 342, 348, 349, 351, 352, 353, 362, 369 Predisposition, 31, 351 Premenopausal, 33, 351 Presumptive, 92, 234, 352 Prevalence, 5, 33, 74, 80, 90, 93, 99, 113, 139, 168, 352 Prickle, 332, 352 Primary Biliary Cirrhosis, 106, 352 Probe, 23, 60, 63, 84, 92, 222, 233, 236, 352 Prodrug, 142, 197, 198, 352 Progeny, 56, 306, 352 Progesterone, 352, 363 Progression, 20, 59, 291, 352

386 E. coli

Progressive, 300, 303, 309, 312, 323, 332, 339, 340, 341, 349, 352, 356 Projection, 309, 342, 352, 356 Prokaryotic Cells, 41, 352 Proline, 91, 178, 215, 220, 304, 352 Promoter, 24, 60, 67, 96, 100, 102, 104, 185, 215, 219, 239, 352 Promotor, 352, 357 Prone, 10, 352 Proneness, 47, 352 Prophase, 297, 340, 343, 352, 365 Prophylaxis, 203, 342, 352, 370 Proportional, 203, 313, 344, 352 Prostate, 137, 266, 352 Protease, 45, 51, 79, 86, 99, 106, 124, 182, 227, 353 Protein Conformation, 152, 157, 290, 331, 353 Protein Engineering, 10, 19, 138, 232, 353 Protein Folding, 45, 177, 353 Protein Subunits, 66, 353 Proteoglycans, 208, 317, 353 Proteolytic, 45, 124, 140, 170, 290, 305, 314, 317, 345, 349, 353 Prothrombin, 353, 366 Protocol, 49, 353 Proton Pump, 15, 353 Protons, 290, 326, 331, 353, 355 Proto-Oncogene Proteins, 345, 353, 354 Proto-Oncogene Proteins c-mos, 345, 354 Protozoa, 22, 297, 306, 338, 354, 362 Psoralen, 153, 158, 354 Psoriasis, 340, 354 Psychology, 311, 354 Public Health, 5, 65, 134, 165, 170, 233, 248, 264, 354 Public Policy, 263, 354 Publishing, 67, 354 Pulmonary, 14, 298, 302, 306, 332, 333, 354, 365 Pulmonary Edema, 302, 332, 354 Pulse, 339, 354 Purifying, 10, 204, 205, 221, 225, 354 Purines, 38, 61, 95, 296, 354, 360 Purpura, 4, 245, 354 Pustular, 328, 354 Putrescine, 288, 354, 362 Pyelonephritis, 78, 120, 141, 147, 228, 244, 354 Pyogenic, 316, 355, 360 Pyridoxal, 289, 321, 355

Q Quality of Life, 355, 364 Quaternary, 353, 355 Quinones, 40, 355 R Radiation, 10, 56, 61, 109, 131, 308, 314, 318, 319, 331, 334, 355, 372 Radioactive, 309, 326, 331, 339, 342, 355 Radioisotope, 53, 355, 367 Randomized, 131, 189, 312, 355 Reactivation, 28, 355 Reactive Oxygen Species, 35, 355 Reading Frames, 54, 355 Reagent, 207, 229, 302, 311, 334, 355 Recombinant Proteins, 78, 222, 355 Recombination, 21, 23, 24, 48, 52, 55, 56, 91, 96, 102, 178, 238, 306, 355 Reconstitution, 66, 141, 153, 158, 355 Rectal, 118, 125, 355 Rectum, 293, 298, 305, 311, 318, 319, 328, 329, 332, 353, 355 Red blood cells, 315, 324, 355, 358, 361 Red Nucleus, 294, 356 Reductase, 27, 68, 69, 81, 100, 101, 137, 139, 183, 185, 217, 218, 227, 235, 294, 356, 366 Refer, 1, 299, 305, 318, 319, 324, 334, 342, 356, 360 Refraction, 356, 362 Refractory, 201, 313, 356 Regeneration, 318, 355, 356 Regimen, 49, 312, 356 Regulon, 9, 31, 35, 49, 82, 88, 153, 158, 187, 356 Rehydration, 4, 145, 356 Remission, 145, 356 Remission Induction, 145, 356 Remission induction therapy, 145, 356 Renal failure, 48, 245, 356 Renal tubular, 48, 356 Renin, 291, 356 Repressor, 9, 51, 77, 99, 153, 158, 343, 356 Research Design, 49, 356 Resolving, 31, 356 Resorption, 325, 356 Respiration, 65, 300, 339, 344, 356 Respiratory distress syndrome, 133, 357 Response Elements, 42, 357 Restoration, 355, 356, 357, 372 Retina, 306, 333, 357, 358 Retinal, 55, 357 Retinoblastoma, 266, 357

Index 387

Retinol, 357 Retrovirus, 222, 357 Reversion, 21, 357, 369 Rheumatism, 357 Rheumatoid, 221, 344, 357 Rheumatoid arthritis, 221, 357 Rhinitis, 357, 360 Ribonuclease, 50, 96, 123, 179, 185, 357 Ribonucleic acid, 201, 357, 358 Ribose, 52, 96, 288, 357 Ribosome, 79, 98, 102, 153, 158, 169, 195, 230, 292, 357, 361, 368 Rigidity, 349, 358 Risk factor, 25, 28, 33, 140, 358 Ristocetin, 358, 370 Rod, 295, 296, 316, 332, 334, 358, 372 Rotavirus, 111, 135, 358 Rubber, 117, 287, 358 S Saline, 349, 358 Saliva, 105, 107, 358 Salivary, 144, 311, 345, 358, 364 Salivary glands, 311, 358 Salmonella typhi, 19, 49, 53, 94, 100, 101, 210, 211, 215, 358 Salmonella typhimurium, 19, 53, 94, 101, 210, 211, 215, 358 Saponins, 358, 363 Saprophyte, 295, 358 Satellite, 24, 358 Saturated fat, 152, 157, 358 Scarlet Fever, 206, 359 Sclerosis, 267, 339, 359 Screening, 16, 31, 54, 74, 75, 81, 110, 146, 177, 196, 200, 212, 223, 238, 239, 304, 359 Sebaceous, 359, 371 Second Messenger Systems, 341, 359 Secondary tumor, 337, 359 Secretory, 4, 30, 34, 85, 141, 359, 365 Sedative, 334, 359 Segregation, 296, 303, 355, 359 Seizures, 345, 359 Selenium, 151, 156, 359 Selenocysteine, 99, 137, 139, 359 Selenomethionine, 17, 359 Semen, 352, 359 Seminiferous tubule, 329, 359, 362 Semisynthetic, 125, 291, 359 Sensitization, 125, 360 Sensor, 27, 54, 60, 166, 180, 181, 229, 360 Sepsis, 17, 58, 107, 134, 140, 206, 214, 237, 360

Septal, 71, 74, 360 Septic, 11, 117, 221, 360 Septicaemia, 360 Septum, 78, 166, 223, 360 Septum Pellucidum, 360 Sequencing, 51, 55, 56, 97, 185, 203, 230, 350, 360 Serine, 26, 62, 70, 112, 137, 153, 158, 215, 216, 220, 287, 303, 314, 354, 360, 364, 368 Serologic, 327, 360 Serotypes, 47, 70, 73, 78, 97, 134, 146, 195, 209, 345, 360 Serous, 305, 314, 360 Serum Albumin, 13, 360 Sex Determination, 267, 360 Shedding, 49, 96, 98, 166, 168, 360 Shock, 11, 44, 50, 58, 59, 96, 117, 171, 195, 200, 221, 360, 368 Side effect, 19, 255, 257, 288, 297, 334, 360, 364, 367 Sigma Factor, 58, 59, 96, 124, 182, 361 Signal Recognition Particle, 70, 82, 361 Signal Transduction, 23, 41, 74, 87, 127, 226, 361 Signs and Symptoms, 356, 361 Sil, 87, 101, 102, 139, 361 Silage, 121, 332, 334, 361 Skeleton, 197, 287, 331, 361 Skull, 307, 361, 365 Sludge, 105, 361 Small intestine, 209, 296, 300, 303, 312, 314, 325, 326, 330, 361, 368, 371 Smooth muscle, 291, 294, 299, 325, 361, 364 Sneezing, 360, 361 Soft tissue, 298, 319, 361 Solid tumor, 291, 297, 312, 361 Solvent, 40, 79, 236, 296, 316, 321, 344, 361 Somatic, 325, 336, 338, 347, 361 Sorbitol, 71, 74, 98, 234, 361 Soybean Oil, 351, 362 Space Flight, 244, 362 Spastic, 226, 331, 362 Spasticity, 362 Specialist, 276, 311, 362 Spectrum, 4, 56, 71, 77, 85, 89, 99, 101, 110, 212, 239, 245, 342, 362, 372 Sperm, 19, 62, 291, 303, 359, 362 Spermatozoa, 359, 362 Spermicide, 5, 362 Spermidine, 93, 288, 362

388 E. coli

Spinal cord, 298, 301, 302, 303, 312, 314, 337, 341, 345, 347, 362 Spinous, 315, 332, 362 Spirochete, 200, 362 Spleen, 58, 335, 362 Sporadic, 83, 90, 113, 236, 357, 362 Spores, 223, 295, 362 Stabilization, 27, 362 Staphylococcus, 8, 16, 22, 168, 180, 185, 202, 320, 328, 362, 363 Staphylococcus aureus, 16, 22, 168, 202, 320, 328, 363 Stem Cells, 112, 322, 363 Steroid, 137, 293, 296, 307, 358, 363 Stimulant, 299, 325, 363 Stimulus, 14, 312, 331, 363, 366 Stomach, 209, 274, 287, 311, 316, 319, 320, 325, 340, 346, 347, 361, 362, 363 Stool, 7, 74, 328, 331, 332, 363 Strand, 56, 77, 178, 179, 204, 222, 350, 363 Streptavidin, 112, 363 Streptococcal, 134, 206, 363 Streptococci, 21, 328, 335, 359, 363 Streptococcus, 22, 138, 206, 315, 363 Stroke, 191, 262, 300, 363 Stromal, 298, 363 Stromal Cells, 298, 363 Styrene, 358, 363 Subacute, 328, 364 Subclinical, 328, 359, 364 Subcutaneous, 301, 312, 319, 335, 343, 364 Submaxillary, 315, 364 Subspecies, 362, 364 Substance P, 155, 315, 337, 355, 358, 359, 364 Substrate Specificity, 12, 17, 27, 38, 41, 43, 62, 79, 99, 364 Subtilisin, 227, 364 Suction, 318, 364 Sulfadiazine, 244, 364 Sulfates, 125, 364 Sulfur, 27, 35, 311, 317, 337, 364 Sulfuric acid, 364 Superoxide, 35, 78, 87, 239, 364 Superoxide Dismutase, 35, 78, 87, 239, 364 Supportive care, 22, 36, 59, 364 Suppression, 78, 99, 342, 364 Suppressive, 136, 364 Suppurative, 206, 301, 319, 364 Surfactant, 143, 365 Sympathomimetic, 312, 315, 342, 365 Symphysis, 352, 365

Symptomatic, 5, 170, 239, 365 Synapses, 341, 365 Synaptic, 361, 365 Synergistic, 54, 79, 91, 365 Systemic, 11, 23, 25, 34, 49, 58, 130, 152, 157, 201, 223, 298, 315, 326, 328, 330, 343, 365, 368 T Tachycardia, 295, 365 Tachypnea, 295, 365 Teichoic Acids, 322, 365 Telangiectasia, 267, 365 Temazepam, 110, 365 Temporal, 24, 32, 120, 214, 336, 365 Teratogenic, 290, 365 Terminator, 304, 365 Testicular, 293, 365 Testosterone, 356, 365 Tetracycline, 175, 219, 365 Tetracycline Resistance, 219, 365 Thalamic, 294, 366 Thalamic Diseases, 294, 366 Theophylline, 354, 366 Therapeutics, 8, 58, 126, 142, 167, 256, 366 Thermal, 185, 187, 204, 205, 221, 225, 311, 342, 350, 366 Thioredoxin, 27, 101, 119, 137, 139, 227, 366 Thoracic, 310, 366, 372 Threonine, 42, 229, 354, 360, 366 Threshold, 58, 326, 366 Thrombin, 40, 317, 349, 353, 366 Thrombocytopenia, 4, 7, 245, 324, 366 Thrombolytic, 349, 366 Thrombomodulin, 40, 353, 366 Thrombosis, 40, 48, 125, 140, 353, 363, 366 Thrombus, 307, 328, 349, 366 Thymidine, 366 Thymidylate Synthase, 18, 108, 366 Thymus, 175, 327, 335, 366 Thyroid, 42, 331, 366, 367, 368, 369 Thyroid Gland, 367, 368 Thyroxine, 289, 348, 367 Tinnitus, 344, 367 Tissue Culture, 44, 66, 186, 197, 367 Tolerance, 53, 75, 98, 163, 185, 288, 367 Tomography, 45, 367 Tonsillitis, 359, 367 Tooth Preparation, 288, 367 Topical, 316, 326, 345, 347, 367 Toxicity, 35, 115, 165, 186, 201, 207, 248, 312, 358, 367

Index 389

Toxicology, 264, 367 Toxins, 13, 25, 33, 34, 36, 48, 80, 226, 227, 228, 247, 292, 297, 313, 321, 328, 339, 360, 367 Toxoplasmosis, 38, 364, 367 Trace element, 304, 367 Tracer, 325, 367 Trachea, 366, 367 Transcriptase, 91, 222, 357, 367 Transcription Factors, 63, 137, 357, 368 Transduction, 101, 238, 361, 368 Transfection, 297, 368 Transfer Factor, 327, 368 Transferases, 216, 368 Transgenes, 24, 368 Translation, 27, 62, 182, 195, 199, 219, 292, 316, 355, 368 Translational, 49, 54, 195, 368 Translocate, 58, 368 Translocation, 14, 31, 45, 87, 92, 316, 368 Transmitter, 287, 312, 331, 336, 342, 365, 368 Transplantation, 6, 298, 303, 327, 332, 335, 368 Trauma, 341, 368 Trees, 290, 349, 358, 368 Triad, 245, 368 Trimethoprim-sulfamethoxazole, 5, 368 Trypsin, 227, 303, 314, 368 Trypsin Inhibitors, 227, 368 Tsh, 95, 368 Tuberculosis, 15, 22, 51, 55, 88, 98, 199, 223, 248, 306, 340, 368 Tuberous Sclerosis, 267, 369 Tumor Necrosis Factor, 73, 90, 122, 369 Tylosin, 12, 369 TYPHI, 49, 211, 369 Typhimurium, 11, 19, 74, 76, 119, 152, 157, 180, 181, 211, 369 Typhoid fever, 345, 358, 369 Tyrosine, 14, 42, 123, 144, 187, 208, 218, 312, 369 U Ubiquinone, 40, 85, 86, 185, 369 Ubiquitin, 45, 369 Ulcer, 301, 369 Ulceration, 339, 369 Ulcerative colitis, 118, 226, 329, 369 Unconscious, 309, 326, 369 Uracil, 38, 124, 154, 159, 178, 369 Urea, 53, 332, 369 Uremia, 129, 332, 356, 369

Ureters, 369 Urethra, 346, 352, 369, 370 Urinary tract, 5, 7, 8, 29, 31, 33, 35, 44, 114, 118, 123, 125, 126, 132, 136, 139, 141, 228, 237, 295, 340, 342, 369 Urine, 5, 7, 29, 94, 293, 295, 297, 305, 311, 315, 324, 328, 332, 342, 343, 369, 370 Urogenital, 135, 223, 320, 370 Urokinase, 119, 370 Uroporphyrinogen Decarboxylase, 204, 370 Uterus, 302, 344, 352, 370 V Vaccination, 49, 199, 220, 223, 240, 370 Vaccine, 17, 37, 47, 49, 55, 113, 195, 200, 210, 211, 214, 220, 222, 230, 252, 288, 353, 370 Vacuoles, 144, 344, 370 Vagina, 296, 302, 310, 332, 370 Vaginal, 7, 33, 146, 370 Vancomycin, 87, 202, 370 Vascular, 23, 25, 36, 48, 209, 314, 328, 342, 343, 348, 349, 366, 367, 370 Vasodilator, 298, 312, 325, 370 Vector, 9, 24, 42, 142, 146, 201, 203, 213, 219, 223, 225, 229, 230, 235, 239, 329, 345, 368, 370 Vegetable Proteins, 349, 370 Vegetative, 297, 370 Vein, 330, 342, 358, 370 Venom, 227, 370 Venous, 298, 301, 343, 349, 353, 370 Venous blood, 298, 301, 349, 370 Ventricles, 302, 325, 360, 370 Ventricular, 326, 370 Venules, 298, 299, 314, 370 Vertigo, 344, 370 Vesicular, 299, 323, 324, 371 Vesicular Exanthema of Swine, 299, 371 Vesicular Exanthema of Swine Virus, 299, 371 Veterinary Medicine, 152, 154, 157, 159, 165, 263, 371 Vibrio, 74, 94, 207, 274, 302, 371 Vibrio cholerae, 74, 302, 371 Villi, 325, 371 Vinculin, 146, 371 Viral, 24, 41, 59, 66, 118, 124, 205, 211, 222, 299, 313, 322, 329, 357, 368, 371, 372 Viral vector, 211, 371 Virion, 295, 343, 371 Virulent, 72, 89, 123, 210, 239, 371

390 E. coli

Vitiligo, 354, 371 Vitro, 10, 11, 19, 22, 26, 27, 32, 33, 40, 43, 45, 46, 47, 49, 50, 52, 56, 57, 58, 66, 80, 84, 87, 95, 106, 121, 123, 126, 133, 140, 165, 216, 228, 240, 324, 328, 350, 358, 367, 371 Vivo, 10, 11, 19, 22, 23, 37, 45, 46, 47, 48, 51, 52, 53, 55, 56, 65, 66, 80, 87, 96, 110, 125, 144, 177, 216, 217, 298, 324, 328, 344, 371 Vulgaris, 172, 175, 371 W War, 302, 340, 372 Warts, 325, 372 Weight Gain, 372 White blood cell, 48, 287, 292, 296, 305, 328, 333, 335, 339, 340, 342, 349, 372

Windpipe, 366, 372 Withdrawal, 344, 372 Wound Healing, 318, 336, 372 X Xanthine, 38, 94, 130, 372 Xenobiotics, 20, 372 Xenograft, 292, 372 X-ray, 17, 24, 27, 38, 41, 42, 44, 51, 61, 62, 64, 131, 187, 198, 318, 319, 340, 342, 372 Y Yeasts, 319, 330, 348, 372 Yersinia, 69, 123, 181, 227, 372 Yersinia enterocolitica, 227, 372 Yersinia pseudotuberculosis, 372 Z Zygote, 306, 372 Zymogen, 303, 353, 372

Index 391

392 E. coli

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Foot and Mouth Disease - A Medical Dictionary, Bibliography, and Annotated Research Guide to Internet References

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