Tetanus - A Medical Dictionary, Bibliography, and Annotated Research Guide to Internet References

TETANUS A M EDICAL D ICTIONARY , B IBLIOGRAPHY , AND A NNOTATED R ESEARCH G UIDE TO I NTERNET R EFERENCES J AMES N. P ...

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TETANUS A M EDICAL D ICTIONARY , B IBLIOGRAPHY , AND A NNOTATED R ESEARCH G UIDE TO I NTERNET R EFERENCES

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 ©2004 by ICON Group International, Inc. Copyright ©2004 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., 1960Tetanus: 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: 0-597-84092-X 1. Tetanus-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 tetanus. 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 TETANUS ................................................................................................... 3 Overview........................................................................................................................................ 3 The Combined Health Information Database................................................................................. 3 Federally Funded Research on Tetanus ......................................................................................... 8 E-Journals: PubMed Central ....................................................................................................... 62 The National Library of Medicine: PubMed ................................................................................ 68 CHAPTER 2. NUTRITION AND TETANUS ....................................................................................... 115 Overview.................................................................................................................................... 115 Finding Nutrition Studies on Tetanus ...................................................................................... 115 Federal Resources on Nutrition ................................................................................................. 119 Additional Web Resources ......................................................................................................... 119 CHAPTER 3. ALTERNATIVE MEDICINE AND TETANUS ................................................................. 121 Overview.................................................................................................................................... 121 National Center for Complementary and Alternative Medicine................................................ 121 Additional Web Resources ......................................................................................................... 132 General References ..................................................................................................................... 134 CHAPTER 4. DISSERTATIONS ON TETANUS ................................................................................... 135 Overview.................................................................................................................................... 135 Dissertations on Tetanus ........................................................................................................... 135 Keeping Current ........................................................................................................................ 135 CHAPTER 5. CLINICAL TRIALS AND TETANUS .............................................................................. 137 Overview.................................................................................................................................... 137 Recent Trials on Tetanus ........................................................................................................... 137 Keeping Current on Clinical Trials ........................................................................................... 139 CHAPTER 6. PATENTS ON TETANUS .............................................................................................. 141 Overview.................................................................................................................................... 141 Patents on Tetanus .................................................................................................................... 141 Patent Applications on Tetanus................................................................................................. 176 Keeping Current ........................................................................................................................ 186 CHAPTER 7. BOOKS ON TETANUS ................................................................................................. 187 Overview.................................................................................................................................... 187 Book Summaries: Federal Agencies............................................................................................ 187 Book Summaries: Online Booksellers......................................................................................... 188 The National Library of Medicine Book Index ........................................................................... 189 Chapters on Tetanus .................................................................................................................. 190 CHAPTER 8. MULTIMEDIA ON TETANUS ....................................................................................... 193 Overview.................................................................................................................................... 193 Bibliography: Multimedia on Tetanus ....................................................................................... 193 CHAPTER 9. PERIODICALS AND NEWS ON TETANUS .................................................................... 195 Overview.................................................................................................................................... 195 News Services and Press Releases.............................................................................................. 195 Academic Periodicals covering Tetanus..................................................................................... 197 CHAPTER 10. RESEARCHING MEDICATIONS ................................................................................. 199 Overview.................................................................................................................................... 199 U.S. Pharmacopeia..................................................................................................................... 199 Commercial Databases ............................................................................................................... 201 APPENDIX A. PHYSICIAN RESOURCES .......................................................................................... 205 Overview.................................................................................................................................... 205 NIH Guidelines.......................................................................................................................... 205 NIH Databases........................................................................................................................... 207

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Other Commercial Databases..................................................................................................... 210 APPENDIX B. PATIENT RESOURCES ............................................................................................... 211 Overview.................................................................................................................................... 211 Patient Guideline Sources.......................................................................................................... 211 Finding Associations.................................................................................................................. 220 APPENDIX C. FINDING MEDICAL LIBRARIES ................................................................................ 223 Overview.................................................................................................................................... 223 Preparation................................................................................................................................. 223 Finding a Local Medical Library................................................................................................ 223 Medical Libraries in the U.S. and Canada ................................................................................. 223 ONLINE GLOSSARIES................................................................................................................ 229 Online Dictionary Directories ................................................................................................... 233 TETANUS DICTIONARY............................................................................................................ 235 INDEX .............................................................................................................................................. 327

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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 tetanus is indexed in search engines, such as www.google.com or others, a non-systematic 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 tetanus, 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 tetanus, 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 tetanus. 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 tetanus, 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 tetanus. The Editors

1 From

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

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

The Combined Health Information Database The Combined Health Information Database summarizes studies across numerous federal agencies. To limit your investigation to research studies and tetanus, 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 “tetanus” (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: •

Autoimmune Prostatitis: Evidence of T Cell Reactivity with Normal Prostatic Proteins Source: Urology. 50(6): 893-899. 1997. Summary: Chronic prostatitis is a common diagnosis, but the disease is poorly understood. Men present with pelvic pain, irritative voiding symptoms, and sexual dysfunction complaints, all of which are nonspecific. This article reports on a study undertaken to determine whether men with chronic prostatitis or chronic pelvic pain syndrome have evidence of an autoimmune response to prostatic proteins. The authors examined men with a history of this problem for evidence of T lymphocyte reactivity to seminal plasma. Patients underwent automated leukopheresis to obtain peripheral blood mononuclear cells. The authors performed a recall antigen proliferation assay to detect specific proliferation of peripheral helper T lymphocytes in men with chronic prostatitis or chronic pelvic pain syndrome and compared the results with those of

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normal men. The antigen for these studies consisted of seminal plasma from normal donors and men with seminal vesicle atresia. A specific recall proliferative response to seminal plasma was observed in 3 of 10 men with a history of chronic prostatitis or chronic pelvic pain syndrome compared with none of 15 normal men. The recall responses of both the syndrome group and the normal subjects to the recall antigens tetanus toxoid and Candida extract were equivalent. The authors conclude that the data represent the first direct evidence that some men with chronic prostatitis or chronic pelvic pain syndrome have an autoimmune component to their disease. Autoimmunity is a potential etiology for chronic nonbacterial prostatitis. 2 figures. 3 tables. 24 references. •

Association Between Administration of Hepatitis B Vaccine at Birth and Completion of the Hepatitis B and 4:3:1:3 Vaccine Series Source: JAMA. Journal of the American Medical Association. 284(8): 978-983. August 2330, 2000. Summary: The association between infant age at initiation of hepatitis B vaccination and completion of the 3 dose hepatitis B vaccination series is unclear. This article reports on a study undertaken to assess the association between administration of the first dose of hepatitis B vaccine within 7 days of birth and completion of the hepatitis B vaccine series and the 4:3:1:3 vaccine series (4 doses of diphtheria tetanus pertussis vaccine, 3 doses of polio vaccine, 1 dose of measles containing vaccine, and 3 doses of Haemophilus influenzae type b vaccine). The study included an analysis of data from the 1998 National Immunization Survey, a random digit dialing telephone survey (n = 34,480 complete interviews) of parents of children aged 19 to 35 months from 50 states and 28 selected urban areas in the United States that included a provider record check mail survey. Overall, 86.9 percent of children 19 to 35 months of age in 1998 received 3 or more doses of hepatitis B vaccine, and 79.9 percent completed the 4:3:1:3 vaccine series. Analysis indicated that, compared with children who received the first hepatitis B vaccine dose within 7 days of birth, odds ratios for not completing the 3 dose hepatitis B vaccine series increased as the time from birth increased. The authors hypothesize that the significant association between age at administration of the first dose of hepatitis B vaccine and completion of the 3 dose series may reflect clinician concerns about parental resistance to multiple injections during a single visit. The authors conclude that administration of the first dose of hepatitis B vaccine at birth is associated with increased likelihood of completion of the hepatitis B vaccination series. Because of this and other advantages, providers should strongly consider a hepatitis B vaccination schedule that initiates vaccination at birth. 1 figure. 2 tables. 23 references.

•

Clinical Epidemiology of Otitis Media Source: Pediatric Infectious Disease Journal. 19(5 Supplement): S31-S36. May 2000. Contact: Available from Lippincott Williams and Wilkins. 12107 Insurance Way, Hagerstown, MD 21740. (800) 637-3030. Fax (301) 824-7390. Website: www.lww.com. Summary: The impact of otitis media (OM, middle ear infection) on public health is considerable. This article explores the clinical epidemiology of OM. OM, with its peak incidence in the first 2 years of life, is the most commonly diagnosed pediatric disease. Between 1993 and 1995, OM was the most common diagnosis during office visits among 1 to 4 year olds. OM constituted 18 percent of physician visits, compared with 14 percent of visits for well child care, 11 percent of visits for upper respiratory infection, 8 percent of visits for injury, and 5 percent of visits for sore throat and tonsillitis. Thirty percent of

Studies

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children younger than 24 months in a large managed care organization were treated with tympanostomy (ventilation) tubes in 1994, and cost of OM treatment in the United States was estimated at $3.8 billion in 1995. Additionally, OM was one of the most common reasons for postponing vaccination for diphtheria, tetanus, pertussis, polio, measles, mumps, and rubella; postponement of the vaccine increases a child's risk for these preventable diseases. The authors conclude that identified host characteristics are useful in targeting high risk children, and well defined environmental factors present potential avenues of primary prevention. Vaccines currently being field tested offer promise for primary prevention, and strategies for risk factor reduction should be tested and implemented. 33 references. •

Management of Facial Dog Bite Injuries Source: Journal of Oral and Maxillofacial Surgery. 53(4): 435-441. April 1995. Summary: The purpose of this article is to provide the oral and maxillofacial surgeon with a comprehensive review of the incidence, pathophysiology, diagnosis, and management of facial dog bite injuries (FDBI). Topics covered include the pathophysiology of dog bite injuries; the initial evaluation, including an intraoral examination; antibiotic prophylaxis; the surgical management of FDBIs; and rabies and tetanus prophylaxis. The authors call for careful and thorough documentation as approximately one-third of dog bite injuries end up in litigation. Two algorithms for care are included. 2 figures. 2 tables. 52 references.

•

Are Vaccines Safe for People With IBD? Source: Foundation Focus. p. 13. November 1991. Contact: Available from Crohn's and Colitis Foundation of America, Inc. 386 Park Avenue South, 17th Floor, New York, NY 10016-8804. (800) 343-3637 or (800) 932-2423 or (212) 685-3440. Summary: This article considers commonly used vaccines and their safety for people with inflammatory bowel diseases (IBD), such as Crohn's disease or ulcerative colitis. In general, vaccines may be administered to children and adults who have IBD in the same way as to the general population. The author details the few important exceptions to this rule and then reviews the following vaccines: influenza, pneumococcal, polio, typhoid, cholera, measles, mumps, rubella, diphtheria, tetanus, pertussis, hepatitis B, and gamma globulin.

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Fending Off the Flu and Other Preventable Diseases Source: Diabetes Self-Management. 16(6): 82-83. November-December 1999. Contact: Available from R.A. Rapaport Publishing, Inc. 150 West 22nd Street, New York, NY 10011. (800) 234-0923. Summary: This article presents guidelines for receiving various types of vaccinations. Many deaths occur in the United States from vaccine preventable deaths. The article identifies the people who should and should not receive influenza; pneumonia; hepatitis A and B; tetanus and diphtheria; measles, mumps, and rubella; and chicken pox vaccinations. In addition, the article explains when and how often these vaccinations should be received.

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Systemic Dissemination as a Result of Oral Infection in Individuals 50 Years of Age and Older Source: SCD. Special Care in Dentistry. 15(1): 11-19. January-February 1995. Contact: Available from Special Care Dentistry. 211 East Chicago Avenue, Chicago, IL 60611. (312) 440-2660. Fax (312) 440-2824. Summary: This article provides a literature review (1980-1994) focusing on welldocumented cases in which systemic disorders were caused by oral foci of infections. Systemic disorders addressed include brain abscesses, meningitis, mediastinal abscesses, bacterial endocarditis, aspiration pneumonia, vertebral osteomyelitis, prosthetic joint infection, gastritis and ulcers, hepatobiliary diseases, chronic urticaria, fever of unknown origin, tetanus, and gangrene of the tongue. The authors attempt to raise the level of awareness of practitioners in considering possible systemic complications caused by oral infection. They also emphasize the need for further longitudinal studies in this field involving healthy and medically compromised elderly individuals. 1 table. 60 references. (AA-M).

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Treating Trismus Source: ADVANCE for Speech-Language Pathologists and Audiologists. 8(30): 22-23. July 27, 1998. Contact: Available from Merion Publications, Inc. 650 Park Avenue, Box 61556, King of Prussia, PA 19406-0956. (800) 355-5627, ext. 279. E-mail: [email protected]. Website: www.advanceweb.com. Summary: This article, from a professional newspaper for speech language pathologists and audiologists, discusses the treatment of patients with trismus. Speech language pathologists most often encounter trismus in patients who are receiving radiation treatment for head and neck cancer. In some cases, muscles involved with mastication may undergo spasms and result in an inability to open the jaw. The author describes a treatment approach that includes working with patients before they undergo radiation treatment and starting range of motion exercises to prevent reduced jaw opening. In addition to radiation treatment for cancer, other causes of trismus include tetanus and other neurological and muscular disorders that can affect the temporomandibular joint (TMJ). Regardless of the cause, people with trismus have difficulty with speech and eating. Treatment may include using wooden tongue blades, or depressors, placed between the teeth and progressively increasing the number of blades as the mouth opens wider; not all clinicians, however, advise this approach. Trismus also complicates the use of oral prostheses by patients with oral cancer or partial or total glossectomies because they can't open their mouths wide enough for a dental professional to take a mold for their prosthesis. The article concludes with the contact information for two of the clinicians and researchers quoted in the article.

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Skin and Wound Infections: An Overview Source: American Family Physician. 57(10): 2424-2432. May 15, 1998. Contact: American Academy of Family Physicians. 11400 Tomahawk Creek Parkway, Leawood, KS 66211-2672. (800) 274-2237 or (913) 906-6000. E-mail: [email protected]. Website: www.aafp.org. Summary: This journal article for health professionals presents an overview of skin and wound infections, focusing on their features and treatment. Skin infections are common

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and may be caused by bacteria, fungi, or viruses. Breaks in the skin integrity, particularly those that inoculate pathogens into the dermis, frequently cause or exacerbate skin infections. Bacterial skin infections caused by corynebacteria include erythrasma, trichomycosis axillaris, and pitted keratolysis. Staphylococci may cause impetigo, ecthyma, and folliculitis. Streptococcal skin infections include impetigo and erysipelas. Human papillomavirus skin infections present as several different types of warts, depending on the surface infected and its relative moisture, and the patterns of pressure. The many dermatomycoses include tinea capitis, tinea barbae, tinea cruris, tinea manus, tinea pedis, and tinea unguium. Candidal infections occur in moist areas, such as the vulva, mouth, penis, skinfolds, and diaper area. Wounds caused by wood splinters or thorns may results in sporotrichosis. Animal bites may result in complex, serious infections, requiring tetanus and, possibly, rabies prophylaxis in addition to appropriate antibiotic therapy. 3 figures and 28 references. (AA-M). •

Dilemma of High-Pressure Water Jet Injuries, The Source: Physician Assistant. 25(1): 17-20. January 2001. Summary: This journal article provides health professionals with information on high pressure water jet injuries. The hand is the most common site of injury, although injuries to the abdomen, head, neck, and lower extremities can occur. Injuries related to high pressure water jets resemble trauma caused by high velocity missiles. These injuries are often subtle on initial clinical presentation with potentially extensive tissue damage underneath. The pathophysiology of jet pressure injuries involves initial extensive tissue destruction; the tissue's response to noxious substances, resulting in vasculitis, edema, venous obstruction, thrombosis, and cellular death; and inflammation, tissue necrosis, and fibrosis secondary to bacterial and other infections. Patient care involves tissue debridement, appropriate use of antibiotics, and close observation. The article presents a case example to illustrate the use of these treatments to augment wound healing in a high pressure water jet injury of the extremities. The patient was a 39 year old man whose left wrist and right foot were injured by an industrial high pressure water jet. The patient was initially taken to a local emergency center. His wounds were irrigated and sutured, and he was given a tetanus prophylaxis, prescribed oral antibiotics and analgesics, instructed to watch for signs of infection, and discharged. However, he was seen at another trauma center 48 hours later with severe pain in this right foot. Following admission to this facility and appropriate at home care, his wounds healed completely. 1 table and 23 references. (AA-M).

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Transplant: The Process and Evaluation Source: For Patients Only. 12(6): 16-19. November-December 1999. Contact: Available from For Patients Only. 18 East 41st Street, New York, NY 10017. (818) 704-5555. Fax (818) 704-6500. Summary: This patient education article reviews the criteria that hospitals use to determine if a patient is a candidate for kidney transplantation. The only method of determining who is a good candidate for a kidney transplant is to establish contact with a transplant hospital and to obtain an evaluation by a transplant physician. Evaluations are based on an individual's medical history, current health status, and other determining factors. The author reviews the advantages and disadvantages of the transplantation procedure and the tests included in the evaluation process, including a physical evaluation, psychosocial evaluation, financial counseling, and a battery of laboratory tests. Laboratory tests may include blood typing, viral testing, tissue typing,

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panel reactive antibody, crossmatch testing, chest x ray, EKG (echocardiogram), renal ultrasound, and mammogram and gynecological examination (women only). In addition, patients must undergo a complete dental check before they can be listed for a transplant; gums and teeth must be healthy prior to the surgery. Patients also need to have had several vaccinations, including diphtheria and tetanus, pneumonia, flu, and hepatitis B series. The average waiting time on the transplant list varies, but can be 2 years or longer. The author briefly reviews what happens after one is accepted on the waiting list, including the call that an organ is available, the admission to the hospital, the surgery, and the postoperative recovery. The author stresses that the patient is a vital member of his or her own patient care team. 2 figures.

Federally Funded Research on Tetanus The U.S. Government supports a variety of research studies relating to tetanus. 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 tetanus. 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 animals or simulated models to explore tetanus. The following is typical of the type of information found when searching the CRISP database for tetanus: •

Project Title: A PNEUMONIAE

NOVEL

VACCINE/ADJUVANT

FOR

STREPTOCOCCUS

Principal Investigator & Institution: Westerink, M.A. Julie.; Rxkinetix, Inc. 1172 Century Dr, Ste 260 Louisville, Co 80027 Timing: Fiscal Year 2003; Project Start 15-MAY-2003; Project End 14-MAY-2004 Summary: (provided by applicant): The first line of host defense occurs at the mucosal surfaces as the majority of pathogens invade the host through attachment, colonization and/or penetration of these membranes. The mucosal surface is inherently designed to prevent invasion of pathogenic organisms through the development of effective immunity. The potential to generate both a systemic and local immune response makes the mucosal system an attractive site for immunization. Mucosal immunization is associated with several significant advantages including low cost and ease of administration, a reduction in adverse side effects and more widespread acceptance. However, mucosal administration of protein and peptide antigens results in poor immune responses. Aluminum-based mineral salts are the only adjuvants currently approved for use in humans by the U.S. Food and Drug Administration. Although, they have an extensive safety record, aluminum compounds are considered poor mucosal 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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adjuvants. Successful mucosal vaccination is therefore largely dependent on the development of safe, effective mucosal adjuvants and delivery systems that overcome these inherent difficulties. This can be considered the rate-limiting step in development of novel and improved vaccines. RxKinetix Inc. has developed a mucosal vaccine delivery system based on the non-ionic block copolymer, Pluronic (r) F127 (F127), combined with an immunostimulant. F127 has been widely used in a variety of pharmaceutical formulations for its surfactant and protein stabilizing properties without adverse effects. F127-based matrices are characterized by reverse thermogelation, a feature that allows a phase transition from liquid to gel upon reaching physiological temperatures. Therefore, F127 can be administered in liquid form and can act as sustained release depot at body temperature. We have evaluated the potential use of F127 as a component of both systemic and mucosal adjuvant/delivery vehicles by studying the immune response in mice to the antigens tetanus toxoid, diphtheria toxoid and anthrax recombinant protective antigen with F 127 in combination with selected immunomodulators. These studies indicated that IgG antibody responses were significantly enhanced by these adjuvant combinations as compared to antigens mixed with the immunomodulators alone. These enhanced effects suggest that F127 may potentially be synergistic with other immunomodulating agents. In this proposal we wish to expand our present repertoire of agents co-administered with F 127 to include the nontoxic B subunits of enterotoxinogenic Escherichia coli (EtxB) and cholera toxin (CtxB) and to compare them to the previously tested adjuvants. To this purpose we will test these adjuvants in combination with pneumococcal surface protein A, a clinically relevant vaccine candidate, as mucosal antigen. These studies will allow us to select the immunomodulator that is optimally synergistic with F127 and provide the necessary information to advance this product to Phase II studies. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •

Project Title: ACQUISITION OF IMMUNITY TO CYTOMEGALOVIRUS Principal Investigator & Institution: Diamond, Don J.; Professor and Head, Laboratory of Vaccin; City of Hope National Medical Center Duarte, Ca 91010 Timing: Fiscal Year 2001 Summary: CMV infection remains an important problem for transplantation. No successful vaccine has been developed that prevents new infections or even controls existing ones. Pharmacologic treatments have limitations regarding their side effects and the development of resistant strain Asymptomatic CMV-seropositive individuals of survivors of CMV infection after BMT, have an ongoing cytotoxic T lymphocyte (CTL) response to CMV, which can be measured after in vitro stimulation (IVS), either using HLA tetrameter binding or chromium release assay (CRA). The CTL response has multiple targets, however, the response to the tegument protein pp65 predominates in most individuals examined. Although many CTL epitopes have already been mapped from two immunodominant CMV proteins (pp65 and pp150), a significant number have yet been determined, and their elucidation will lead to a broad-based vaccine strategy for all major ethic groups in the United States. Immunodominance of CTL responses to CMV proteins will be determined utilizing IVS strategies together with known CTL epitopes. In contrast, little is known of the predominance of CTL targets from CMV in BMT recipients. The frequency of CMV-specific CTL will be enumerated using flow cytometry with HLA tetramers, and the frequency of those CTL will be compared to viral load measurements using plasma PCR methods. As a means to enhance the immunogenicity of previous defined CTL epitopes, a combinatorial peptide chemistry approach will be used with the known CTL epitopes from pp65 and pp150, which have

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affinities that are in the micromolar to approach will be used with the known CTL epitopes from pp65 and pp150, which have affinities that are in the micromolar to nanomolar range. Analogue peptides will be defined that will be evaluated initially using HLA A*0201 restricted and pp65- specific T cell clones, to develop a more immunogenic CTL epitope which may lead to a more effective CMV vaccine. The functionality of these analogue peptides will be shown utilizing in vivo immunization of HLA-transgenic mice and IVS studies stimulating a memory response in human PBMC specific for killing of CMV infected fibroblasts in vitro. Two Phase II trials will evaluate modalities including CMV lipopeptide immunization in combination with standard tetanus toxin immunization of BMT recipients. Augmentation of the memory response to tetanus- specific CD4+ T cells will be evaluated by in vitro methods, and the duration of infection-free survival of BMT recipients will be measured using standard clinical parameters. Finally, the utility of targeting a single CMV protein utilizing a CTL epitope vaccine strategy versus targeting two or more CMV proteins will be evaluated using CMV lipopeptide immunization of BMT recipients. Since the endpoint of the trial is a reduction in the incidence of CMV-associated disease, the comparison must be done utilizing a patient population likely to have measurable CMV viral load. Taken together, these strategies of defining CTL epitopes, augmenting their immunogenicity, and defining efficacious ways to delay them to CMT recipients will aid in the development of an effective CMV vaccine both as therapeutic and prophylactic agent. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •

Project Title: ACTG377:PHASE II PRAM OF NOVEL ANTIRETROVIRAL THERAPY IN STABLE HIV C Principal Investigator & Institution: Shearer, William T.; Professor of Pediatrics; Baylor College of Medicine 1 Baylor Plaza Houston, Tx 77030 Timing: Fiscal Year 2001 Summary: This is a Phase I/II, multicenter randomized, open label trial of a standard therapeutic regimen in current use versus experimental therapies administered over 48 weeks. At least 200 HIV-infected children ages four months to 17 years of age will be enrolled. The children will be stratified by CD4+% and by age to receive one of four treatment regimens. These treatment regimens are A: d4T/nevirapine/ritonavir, B: d4T/3TC/nelfinavir, C: d4T/nevirapine/nelfinavir or D: d4T/3TC/nevirapine/nelfinavir for 48 weeks. The first 35 subjects per arm will be evaluated with special immunologic studies LPA and extended panel immunophenotyping. Baseline and study safety evaluations will include the monitoring of adverse experiences clinical laboratory tests, physical examinations and vital signs. An assessment of virologic efficacy will occur at the 12 week interim analysis time period. Real-time HIV-1 RNA measurements will occur at weeks 12, 24 and 36. This study will also include two substudies: ACTG 725 A Pharmacokinetic Study of BID Nelfinavir's Dosing Given to Children 10 h in vitro). The two patterns of stimulation are differentially sensitive to different enzymatic poisons: Serine/threonine kinase poison H-7 inhibits PKC, PKA, PKG, and CamKII, and prevents NMDA-dependent LTP induction (25Hz tetanus); tyrosine kinase poisons (e.g. genistein and lavendustin A) did not significantly attenuate 25Hz LTP induction, but prevented the vdccLTP (200Hz stim) from lasting more than 80 minutes. The proposed research will explore the relationship between learning and memory and the mechanisms underlying these two forms of plasticity. Specifically, the PI will test the effects of drugs that selectively block either voltage-dependent or NMDA receptor dependent LTP on memory performance in the radial maze.To test the hypothesis that vdccLTP is required for long-term memory retention, whereas NMDA receptordependent LTP is required for the acquisition of shorter-term reference memory, rats will be trained and tested in the 4/8 task on a radial maze. In this task, food is placed in 4 of the 8 arms of the maze at the start of each trial without replacement, and the task for the rat is to enter each of these baited arms once to get the food most efficiently. Entries into arms that never have food define reference memory errors, and repeated entries into arms with food within a trial define working memory errors (episodic memory). Hippocampal lesions impair acquisition of both working and reference memory in this task, but lesions given after training impair only the working memory component. Two major unanswered questions remain: 1. How does the within-trial working memory persist when NMDA receptors are blocked? 2. How and where in the brain is the longterm reference memory stored? The proposal focuses on the 2nd of these questions. NMDA receptor antagonists and voltage-dependent calcium channel LTP blockers will be given, alone and in combination, to behaving rats. In separate experiments, the drugs will be given systemically and into the hippocampus directly. Dose/response curves for the effects of the drugs on LTP induction will be tested in vivo. The hypothesis is that voltage-dependent LTP is required for long-term memory retention, whereas NMDA receptor dependent LTP is required for the shorter-term acquisition of reference memory. The drugs will also be given in combination. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •

Project Title: MECHANISM OF LUMINAL ACIDIFICATION IN EPIDIDYMIS & VAS DEFERENS Principal Investigator & Institution: Breton, Sylvie; Marine Biological Laboratory 7 Mbl St Woods Hole, Ma 02543 Timing: Fiscal Year 2001 Summary: An acid pH is established in the lumen of the excurrent duct of the male reproductive tract, which is important for sperm maturation as well as for maintaining sperm in a quiescent state during their passage through, and storage in, the epididymis/vas deferens. One major component of the complex series of events that trigger sperm motility during ejaculation is neutralization by the alkaline prostatic fluid, followed by an increase in intracellular pH. The ultimate aim of this research is to understand how defective acidification may impair reproductive function in pathologic states, and how intervention to manipulate acidification may eventually be used to

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control male fertility. A novel physiological approach using the non-invasive selfreferencing proton-selective electrode, in collaboration with Peter Smith, had allowed us to identify the major proton secretory mechanism in the initial part of the vas deferens. We have shown that a bafilomycin-sensitive, proton-pumping H+-ATPase (proton pump - PP) is concentrated in the apical membrane of a subpopulation of epithelial cells (PP-rich cells) and is a major contributer to luminal acidification (1, 2, 3). Our specific aims are 1) to define and characterize the complete pathways of proton secretion by the PP-rich cells; 2) to elucidate the mechanisms of vesicle recycling underlying the regulation of proton secretion; and 3) to examine the effect of some environmental pollutants on proton secretion. 1) Proton secretion pathways: PP-rich cells are enriched in the cytoplasmic carbonic anhydrase type II (CAII) indicating that bicarbonate transport is involved in proton secretion. We have shown, using the proton-selective electrode, that the CAII inhibitor, acetazolamide, markedly inhibits proton secretion by the vas deferens. Subsequent addition of bafilomycin after acetazolamide produced no further inhibitory effect on luminal acidification. The bicarbonate transport inhibitor, SITS (4-acetamido-4'-isothiocyanostilbene-2,2'-disulfonic acid), also inhibits proton secretion to the same extent as bafilomycin. These results suggest that H+ secretion by the PP-rich cells depends on the reabsorption of bicarbonate. Two bicarbonate transporters have been described in various organs including the kidney, the Na-HCO3 cotransporter and the Cl-HCO3 exchanger. We will identify which of these transporters is involved in the vas deferens by examining the effect of SITS in the absence of Na (replaced by N-methyl-D-glucamine) or Cl (replaced by cyclamate). 2) Proton pump recycling: We have shown that endocytic vesicles (labelled with the fluid phase marker, FITC-dextran) contain H+ATPase and are probably involved in the regulation of H+ secretion by the epididymis/vas deferens. In addition, the vesicle-associated protein, cellubrevin, is highly expressed in the PP-rich cells providing further evidence of a regulated endo/exocytotic apparatus in these cells. We have observed a significant inhibition of the proton flux measured using the proton-selective probe after cleavage of cellubrevin by tetanus toxin. This result suggests that H+ATPase activity is modulated, at least partly, via exocytosis of PP-containing vesicles followed by insertion of PP into the apical membrane. 3) Effect of heavy metals on proton secretion: Exposure to lead, cadmium. manganese and mercury has been shown to reduce male reproductive capacity in a variety of species including human. We are examining whether this reduction of male fertility can be attributed to a defect of the acidification capacity of the epididymis and vas deferens. Using the proton-selective probe, we found a marked inhibition of proton secretion in vas deferens accutely exposed in vitro to a heavy metal, cadmium (500mM). This inhibition is of the same amplitude as that observed with either acetazolamide, SITS or bafilomycin, and the latter had no additional effect indicating inhibition of the proton pump by cadmium. Breton, S, Smith, P. J. S., Lui, B. and Brown, D. 1996. Acidification of the male reproductive tract by a proton-pumping ATPase. Nature Medicine 2: 470-472. Breton, S, Smith, P. J. S. and Brown, D. 1997. Presence de cellules acidificantes dans l'epididyme et le canal deferent: implication de la pompe a protons, H+ATPase. Medecine Sciences. (Revue internationale de biologie et de medicine.) 13: 57-61. Brown, D., Smith, P. J. S. and Breton, S. 1997. Role of V-ATPase rich cells in acidification of the male reproductive tract. J. exp. Biol. 200 (2): 257-262. Patent pending: Brown, D., Breton, S., and Smith, P. J. S. 1996. Method of reversibly controlling male fertility. U. S. Patent Application No. 08/826,019. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen

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Project Title: MECHANISM OF NEURONAL CELL DEATH AND RESCUE IN SMA Principal Investigator & Institution: Francis, Jonathan W.; Massachusetts General Hospital 55 Fruit St Boston, Ma 02114 Timing: Fiscal Year 2001; Project Start 19-APR-1999; Project End 31-MAR-2003 Summary: This abstract is not available. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen

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Project Title: METABOLIC IMMUNOTARGETING

ENGINEERING

OF

CANCER

FOR

Principal Investigator & Institution: Guo, Zhongwu; Chemistry; Case Western Reserve University 10900 Euclid Ave Cleveland, Oh 44106 Timing: Fiscal Year 2002; Project Start 01-APR-2002; Project End 31-MAR-2007 Summary: (provided by applicant) Oncogenic transformations are closely correlated with the change of glycosylation patterns of cell surfaces, and the aberrant carbohydrates expressed on tumors, which are called tumor-associated carbohydrate antigens (TACAs), are important targets for the development of cancer vaccines that can be used for cancer diagnosis and therapy. However, the problem of immunotolerance to TACAs has severely hindered further progress in the area. To solve this problem and to develop new, effective cancer vaccines, this project will exploit a new strategy that is based on modified TACAs and metabolic engineering of cancers. First, a TACA on cancer cells will be metabolically modified by treating them with an artificial derivative of a monosaccharide that can be taken as a precursor by cancer cells to biosynthesize a neoantigen - an artificially modified analog of the TACA. The metabolic engineering of cancer takes the advantage of the remarkable flexibility of carbohydrate biosynthetic machineries. Then, specific monoclonal antibodies (mAbs) will be used to selectively target tumor cells labeled by the neoantigen. The mAbs in return can be prepared with a synthetic vaccine made of the neoantigen. As vaccines made of artificial carbohydrates are potentially more immunogenic than those made of the natural TACAs and the metabolic engineering can specifically mark cancer cells, effective vaccines may be easily composed from modified TACAs and the new strategy will potentially solve the problem of immunotolerance to TACAs. The metabolic modifying targets of this project are sialyl TACAs. Melanoma is employed as the tumor model, and GD3 and GM3 on its cells are the specific targets. The N-modified analogs of mannosamine and sialic acid will be used as the precursors, and the neoantigens expressed on melanoma will then be the N-modified derivatives of GD3 and GM3. The aims of this project are: 1)to find the effective precursors for metabolic engineering of melanoma via studying the bioavailability of various precursors to the enzymes involved in the biosynthesis of sialyl TACAs and to melanoma cells; 2) to find the effective vaccines that can provoke specific immune responses to the neoantigens via studying the conjugates of various Nmodified GD3 and GM3; 3) to illustrate the new strategy through specific immunotargeting of metabolically engineered melanoma. This research will eventually establish a proper combination of the precursor and vaccine. As the overexpression of sialic acid is found in various tumors and sialic acid is a shared feature of many TACAs, the principles established herein may be of wide applicability. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen

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Project Title: MICE WITH HUMAN DENDRITIC CELLS TO TEST VACCINE POTENCY Principal Investigator & Institution: Palucka, a Karolina.; Investigator; Baylor Research Institute 3434 Live Oak St, Ste 125 Dallas, Tx 75204 Timing: Fiscal Year 2003; Project Start 01-AUG-2003; Project End 31-JUL-2005 Summary: (provided by applicant): There is a need for pre-clinical models that could be used to evaluate manipulation of the human immune system. This is particularly important for the testing of vaccines such as those currently needed in the context of biowarfare. Conclusions from studies in mouse models cannot be directly extrapolated to humans because of biological differences as exemplified by the pattern of Toll receptors expression on dendritic cells (DCs) and/or by the CD1 antigen presentation system that are different between species. SCID mice represent an interesting candidate however, the use of SCID mice for evaluation of immune responses has not quite fulfilled all its promises. Thus, grafting of PBMCs leads to rather limited immune reconstitution that does not allow development of in vivo human immune responses, particularly priming and affinity maturation. Development of NOD-SCID has brought about an improvement in engraftment of both hematopoietic progenitors and PBL. Yet, many of the difficulties could be due to insufficient reconstitution of DCs, a parameter that has been overlooked in studies up to date. Our preliminary results show that NODSCID mice transplanted with human CD34+ HPCs develop all subsets of human dendritic cells (SCID-hu/DCs mice). Therefore, SCID-hu/DCs mice represents a novel model system to study the physiology of human DCs. We propose to assess the in vivo function of human DCs generated in SCID mice including their capacity to induce vaccine specific cellular (CD4 mediated) and humoral immune responses using Tetanus Toxoid as a model vaccine. Two aims are designed: 1) To determine whether human DCs can induce proliferation of human allogeneic T cells in vivo, and 2) To determine whether human DCs can induce vaccine-specific immune responses in vivo. The experiments proposed here would lay ground for further use of SCID-hu/DCs mice to study other vaccines and demonstrate development of protective immunity upon in vivo rechallenge. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen

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Project Title: MOLECULAR CLONING OF HLA CLASS II TUMOR ANTIGENS Principal Investigator & Institution: Herlyn, Dorothee M.; Professor; Wistar Institute Philadelphia, Pa 191044268 Timing: Fiscal Year 2001; Project Start 06-JUN-2000; Project End 31-MAY-2004 Summary: Our major goal is to develop a novel technology to identify HLA class II tumor antigens using a unique cloning approach in filamentous phages which has not been applied to the cloning of class II antigens in the past. This approach has numerous potential advantage over existing approaches to class II antigen cloning or biochemical peptide isolation. The unique cloning approach proposed here will be applicable to a variety of tumor-associated HLA class II antigens derived from tumors of different histologic types, and also to class II antigens involved in infectious diseases. Active specific immunotherapy has great potential for the treatment of patients with melanoma or colorectal carcinoma (CRC). In light of the important role that CD4+, HLA class IIdependent helper T (TH) cells play in the control of tumor growth, approaches to active immunotherapy with TH cell-defined antigens need to be developed. Very few tumorassociated TH antigens or peptides with vaccine potential have been identified thus far. The long-term goal of the proposed studies is to identify TH antigens with vaccine

38

Tetanus

potential for melanoma and CRC patients. The Th antigens are recognized by available Th lines and clones. A novel approach for the cloning of mammalian HLA class IIdependent Th antigens will be developed using filamentous phages. Tumor cells cDNA libraries will be expressed by the phages, followd by library phage presentation to TH cell by antigen- presenting cells and identification of the relevant Th antigen in cytokine release assay. To develop this approach, we have available a unique model system including Th cells against tetanus toxoid and a cDNA fragment encoding the tetanus toxoid-associated Th epitope. Specifically we will: 1) develop Th antigen cloning technology using filamentous phages and tetanus toxoid as a model system (R21 pilot study); and 2) optimize the filamentous phage HLA class II antigen cloning approach developed under the pilot study to clone melanoma and CRC-associated Th antigens; this will be followed by the identification and characrterization of these antigens (R33). The feasibility of the filamentous phage approach for the cloning of HLA class II antigens is emphasized by the demonstration of successful induction of antigen-specific, Th cell-dependent antibodies in mice by immunizing the mice with phages expressing various antigens. The proposed studies will develop a novel technology to identify HLA class II-dependent Th antigens using filamentous phages leading to novel approaches to active specific cancer immunotherapy using these antigens. The antigens also may be of diagnostic value. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •

Project Title: MOLECULAR MECHANISMS OF THE H. PYLORI VACUOLATING TOXIN Principal Investigator & Institution: Blanke, Steven R.; Associate Professor; Biology and Biochemistry; University of Houston 4800 Calhoun Rd Houston, Tx 77004 Timing: Fiscal Year 2001; Project Start 15-MAR-2000; Project End 28-FEB-2005 Summary: Helicobacter pylori is an etiologic agent of a number of gastric disorders in humans, including peptic ulceration and gastric adenocarcinomas. Early efforts to understand H. pylori pathogenesis revealed the presence of a secreted bacterial toxin (VacA) which mounting evidence indicates is an important virulence factor. VacA causes massive degenerative vacuolation of mammalian cells which has been implicated in the gastric epithelial erosion preceding the onset of peptic ulcer disease. The broad objective of this research program si to elucidate the fundamental mechanisms by which VacA mediates cellular cytotoxicity. Long-term milestones include identification of the biochemical activity and intracellular targets of VacA. Experiments in this proposal are designed to test the hypothesis that VacA mediates cellular cytotoxicity as an AB toxin. The model of VacA as an AB toxin is important because it suggests specific hypotheses directly relevant to the fundamental mechanism by which VacA enters host cells and induces vacuolation. The AB family of toxins share a number of distinct properties, and includes prominent members such as cholera, diphtheria, tetanus, and anthrax toxins. The specific aims in this proposal are designed to elucidate the VacA molecular structure and begin to identify structure-function relationships of the toxins. The specific aims are: [1] To identify cellular mechanisms of VacA cytotoxicity. To achieve these goals, novel VacA fusion proteins will be genetically constructed to determine if VacA is trafficked to the cytosol. In addition, radiolabeled VacA will be analyzed for intracellular proteolytic processing. [2] To identify VacA structural characteristics important to the toxin's cellular activities. To achieve these goals, mutant forms of VacA and novel fusion proteins will be genetically constructed to test hypotheses about VacA structure-function relationships and biochemical activities. Because it is estimated that the prevalence of H. pylori infection in developed countries is 20-50%, and 70-90% in

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developing countries, the importance of developing efficacious vaccines, chemotherapeutics, and diagnostics of H. pylori cannot be overstated. These studies will not only contribute to under understanding of the fundamental mechanisms of VacAmediated cytotoxicity, but may reveal novel strategies for using attenuated VacA, or fragments of VacA is components in new protective vaccines. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •

Project Title: MOTOR NEURON PROTECTION THROUGH GLUTAMATE DEGRADATION Principal Investigator & Institution: Fishman, Paul S.; Neurology; University of Maryland Balt Prof School Baltimore, Md 21201 Timing: Fiscal Year 2001; Project Start 01-AUG-2001; Project End 31-JUL-2003 Summary: (provided by applicant): Glutamate-provoked excitotoxicity may contribute to the pathogenesis of both acute and degenerative neurological disease. Although glutamate re-uptake is the normal manner through which the action of the neurotransmitter is terminated, glutamate can also be eliminated through enzymatic degradation. We have recently created a functionally active hybrid protein that links a glutamate-degrading enzyme (glutamate-pyruvate-transaminase, GPT-also known as ALT) with the non-toxic neuronal binding domain of tetanus toxin (tetanus toxin fragment C or TTC). The rationale for producing this molecule is to deliver an enhanced capacity to enzymatically-degrade glutamate to synaptic regions surrounding motor neurons, and thereby protect them from toxic levels of glutamate. Our previous studies have demonstrated: 1) TTC can dramatically enhance (100 to 1,000 fold) the delivery of active enzyme to neurons in vitro and motor neurons in vivo. 2) TTC-linked enzymes are targeted to synaptic regions surrounding neurons in vitro and motor neurons in vivo. 3) GPT is the most effective enzyme to rapidly (within minutes) reduce neurotoxic levels of glutamate. 4) GPT can protect neurons in vitro from both direct exposure to toxic levels of glutamate and the toxic effect of inhibition of glutamate re-uptake. We propose to assess TTC-GPT in models of chronic glutamate excitotoxicity and motor neuron degeneration. Initially, we will quantitate the uptake and persistence of active enzymes to explant cultures of neo-natal rat spinal cord with both native GPT and TTCGPT. We will then assess the capacity of TTC-GPT to prevent progressive motor neuronal death in these spinal cord cultures exposed to inhibitors of glutamate reuptake, or after reduction of synthesis of high-affinity glutamate transporters using antisense oligonucleotides. We will assess the capacity of TTC-GPT to deliver active enzymes to motor neurons from an intramuscular injection, via retrograde axonal transport, in both normal mice and in a murine model of familial ALS. This proposal will determine the potential of not only glutamate degradation as an anti-excitotoxic strategy, but of TTC as a vector to deliver therapeutic proteins with synaptic sites of action. If successful, TTC-GPT can be assessed in animal models of motor neuron disease, such as the FALS mouse, in the future. These studies will advance understanding of the potential of a novel means of glutamate elimination with therapeutic implications of diseases for not only ALS, but also other neurologic diseases such as stroke, Alzheimer's Disease and Parkinson's Disease. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen

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Project Title: MUCOSAL IMMUNITY AND ORAL TOLERANCE--INNATE IMMUNITY Principal Investigator & Institution: Tackett, Carol O.; Medicine; University of Maryland Balt Prof School Baltimore, Md 21201

40

Tetanus

Timing: Fiscal Year 2001; Project Start 30-SEP-2000; Project End 29-SEP-2002 Summary: The gastrointestinal mucosal immune system has evolved complex and redundant mechanisms to meet two conflicting requirements that both protect the host from invasive pathogens and ensure tolerance to innocuous but potentially antigenic materials that are the products of digestion and the normal flora. The long term goal of this proposal is to study the general hypothesis that the balance between protective immunity and tolerance in the human mucosal immune system is dependent on whether oral immunogens encounter the immune system in a milieu resembling pathogenic invasion or in a non-inflammatory, toleragenic milieu, determined in part by the state of activation of the innate immune system. There is evidence in animal models that one of the many pathways regulating innate immunity involves the cyclooxygenase system. The effects of varying antigen delivery systems, and the effects of pharmacologic modulation of cyclooxygenase pathways on both mucosal immunity and tolerance have not been studied in humans. The approach will encompass systematic measurements of protective immunity and tolerance in humans in response to two very different types of oral challenge, one mimicking an invasive pathogen and the second mimicking the response to harmless food antigens. We will use novel live recombinant enteric bacterial vectors (attenuated S. typhi expressing recombinant tetanus toxoid fragment C) and transgenic plant foods expressing vaccine antigens (transgenic potato expressing hepatitis B surface antigen) to evaluate protective immunity followed by parenteral immunization (tetanus toxoid or hepatitis B surface antigen) to test for tolerance. To study the role of prostaglandins in mucosal immunity and tolerance, volunteers will be randomized to receive either placebo, rofecoxib, a selective cox-2 inhibitor, or misoprostol, a long-acting prostaglandin E1 analog during oral immunization. The results of this study will be the first to address the hypothesis that the mode of antigen delivery and level of prostaglandins modulate the balance between oral immunity and tolerance in humans. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •

Project Title: MULTIPLE-SCLEROSIS: A CD40 LIGAND ANTAGONIST Principal Investigator & Institution: Kasper, Lloyd H.; Professor; Medicine; Dartmouth College 11 Rope Ferry Rd. #6210 Hanover, Nh 03755 Timing: Fiscal Year 2001; Project Start 01-JUL-2001; Project End 30-JUN-2006 Summary: Multiple sclerosis (MS) is a clinical neurological disease characterized by chronic inflammation, demyelination and gliosis of the central nervous system. It is the principal neurologic disease of individuals in early to middle adult life and afflicts as many as 350,000 people in this country. The available therapy for treating and preventing the progression of disease is limited. Recent evidence suggests that early therapeutic intervention may be important in decreasing disease activity. MS is mediated at least in part by T cells, macrophages and to a lesser extent B cells. Activation of T and B cells is dependent upon the interaction of the TCR/MHC as well as co-stimulatory molecules, including CD40-CD40L. CD40 and its ligand have been shown to play a critical role in the regulation of both humoral and cell-mediated immunity. Blockade of CD154 is effective in ameliorating the manifestations of several autoimmune diseases and thus has become an attractive therapeutic target. The interaction of CD40/CD40L has been demonstrated in both the experimental model of experimental allergic encephalomyelitis (EAE) as well as multiple sclerosis. In EAE, antibody blocking of CD40L prevents the progression of disease in both the monophasic and relapsing remitting experimental models. The overall objective of this clinical research trial is to determine whether antibody to CD40L can block the progression of

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enhancing lesions on MRI in those individuals with relapsing- remitting MS (primary outcome). Individuals (n=40) with clinically defined MS (EDSS 0-less than 3.5) will be evaluated for six months by monthly GdDTPA enhanced MRI scans and EDSS to determine disease progression. If eligible (greater than 2 new enhancing lesion 2mm or greater during the 6 month pretreatment phase), these individuals (n=20-24) will be treated with intravenous humanized anti-CD40L (IDEC-131). Patients will be treated for 6 months (total=8 infusions) with 5mg/kg antibody during which time they will continue to undergo monthly Gd enhanced MRI and EDSS evaluation(secondary outcome). We will determine the effect of therapy on MR spectroscopy metabolic, peaks for NAA, choline and creatine (absolute magnitude and ratios) in left and right hemispheric periventricular white matter voxels of interest (secondary outcome). Delay in cerebral atrophy will be evaluated by determining the change in parenchymal brain fraction. We will also develop a novel biological assay to determine efficacy of therapy(secondary outcome). MHCII-Ig fusion proteins that have an embedded MBP peptide will be used to identify MBP-reactive T cells in the peripheral blood of these patients. The polarity (Th1 and Th2) of the MBP-MHCII-Ig binding T cells will be determined as well as their activation status. The impact of in vivo anti-CD40L therapy on the frequency, phenotype and functional status of the MBP-MHCII-Ig binding T cells will be determined in vitro as well as T and B cell recall to tetanus toxoid. An additional secondary outcome will be to assess change in the cognitive impairment index in response to therapy. Neuropsychological variables sensitive to clinical trial outcomes in MS include measures of visual memory and mental flexibility. Follow up will be done with MRI and EDSS at 18 and 24 months after enrollment(secondary outcome). The study will will allow us to achieve a power of 85 percent (32 percent reduction in plaque burden). Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •

Project Title: NANOFLUIDIC DEVICES FOR RECOGNITION OF NEUROTOXINS Principal Investigator & Institution: Bohn, Paul W.; University of Illinois Urbana Champaign, Il 61820 Timing: Fiscal Year 2003; Project Start 04-SEP-2003; Project End 29-FEB-2008 Summary: Effectiveness of antitoxin therapy in the treatment of botulism and tetanus is significantly reduced, if the treatment is not administered shortly after exposure or onset of disease. Rapid diagnosis and early administration of antitoxin therapy is therefore essential for a patient's recovery. Development of detection devices capable of selectively sensing minute quantities of neurotoxins in body fluids will be critical for providing rapid diagnostic assessment. This proposal outlines a program of research leading to the construction and use of a multidimensional nanofluidic device, specifically designed to manipulate samples, which must be handled in extremely small quantities, e.g., the potent neurotoxins from the Clostridium botulinum and C. tetani families. In the proposed approach, electrokinetic and other standard microfluidic flows are exploited to move reactant and product species among the separate compartments of the device, which are integrated using a new biofluidic device, the molecular gate, based on novel membranes developed at UIUC capable of performing important biomolecular manipulations, e.g. affinity binding and molecular sieving, while simultaneously functioning as the switching elements between microfluidic compartments. The specific aims are: Specific Aim 1. Determine the optimum reaction and separation conditions for the toxins. A set of neurotoxin-specific recognition agents will be developed such that the molecular recognition event results in the generation of highly specific and isolatable reaction products. The separation and detection behavior of these reaction products will

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Tetanus

be investigated under conditions appropriate to the nanoscale device to be explored in Specific Aims 2 and 3. Specific Aim 2. Incorporate the separation, reaction and detection processes into the micro/nanofluidic device. Miniaturize the molecular recognition, separation, and detection events and incorporate them into a multidimensional hybrid nanofluidic/microfluidic architecture capable of performing sequential chemical manipulations on ultrasmall volumes of complex biomolecular samples. Specific Aim 3. Multiplex the preseparation, molecular recognition, separation, and detection events appropriate to each of the 7 neurotoxins into a single device. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •

Project Title: NEUROLOGICAL DEFICITS DUE TO TOXIC A BETA OLIGOMERS Principal Investigator & Institution: Klein, William L.; Professor; Neurobiology and Physiology; Northwestern University 633 Clark St Evanston, Il 60208 Timing: Fiscal Year 2001; Project Start 01-AUG-2001; Project End 31-JUL-2004 Summary: (From the Applicant's Abstract): This application concerns a new possibility for the role of Abeta in AD. It is designated to investigate the loss of synaptic plasticity and death of nerve cells caused by nonfibrillar Abeta oligomers. Oligomers accumulate in AD brain, and current best evidence indicates they contribute to disease progression, potentially accounting for the imperfect correlation with amyloid. Aims focus on three key properties of oligomers (referred to as "ADDLs," for Abeta derived diffusable ligands). (i) ADDLs inhibits LTP in under an hour, one of the fastest known responses to any form of Abeta. (ii) ADDLs kill hippocampal neurons by a mechanism blocked by germline knockout of Fyn, a protein tyrosine kinase coupled to NMDA receptors and tetanus-induced LTP. (iii) ADDLs bind to cell surface proteins that are trypsin-sensitive and cluster at punctate "hot spots." The goal is to understand the molecular basis for ADDL neurotoxicity. Two hypotheses will be evaluated. First, ADDLs may be small protein ligands that cause damage by disturbing Fyn signal transduction, a consequence mediated by specific toxin receptors. Alternatively, ADDLs may disrupt cell integrity with little or no specificity, generating a global breakdown of cell physiology that includes loss of LTP and culminates in cell death. Predictions of these hypotheses will be tested by the proposal's AIMs. Aim 1. LTP or neurotransmission-Is the synaptic impact of ADDLs specific for LTP, or is synaptic function broadly impaired. Aim 2. Types of plasticity-Do ADDLs affect multiple types of neuronal plasticity, or only tetanus induced LTP? Aim 3. Molecular impact-Does toxicity stem form ADDLs impact on Fyn, or do ADDLs attack at alternative and perhaps multiple sites? Aim 4. Cell surface reactions-Are ADDLs bound by specific "toxin receptors," or is ADDL activity not dependent on unique binding sites? Results from this application will give a new basis for understanding the actions of Abeta oligomers found in human brain. In a best-case outcome, findings would provide novel targets for therapies that ultimately could reverse and not just slow down AD memory impairment. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen

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Project Title: NEWBORN MORTALITY-NEPAL

ANTISEPTIC

WASHING

AND

NEONATAL

Principal Investigator & Institution: Tielsch, James M.; Professor; International Health; Johns Hopkins University 3400 N Charles St Baltimore, Md 21218 Timing: Fiscal Year 2003; Project Start 06-AUG-2003; Project End 31-JUL-2006 Summary: (provided by applicant): The long-term objective of our research program is to identify cost-effective interventions that can significantly reduce morbidity and

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mortality among young children in the least developed areas of the world. The aims of this project are focused on prevention of neonatal mortality and morbidity using a topical antiseptic agent (chlorhexidine, CHX). Specifically we propose to: (1) compare the neonatal mortality among newborn infants randomized to receive either a whole body wipe with a dilute CHX solution (0.25%) or placebo within the first few hours after birth; (2) compare the rates of umbilical cord infections among newborn infants randomized to receive daily cleansing of the umbilical cord for 7 days after birth with either a 4% CHX solution, a soap and water solution, or nothing. The design of this project consists of two nested cluster-randomized, community-based clinical trials. The study population will be all live-born infants who are delivered in Sarlahi District in southern Nepal where our group is conducting a large micronutrient intervention trial with mortality as the outcome among children 1 to 35 months of age. These two trials will be nested underneath the current trial. The area is divided into 425 sectors that will be randomized to one of two immediate post-delivery treatment groups. Infants born to sectors in the treatment group will receive newborn washing with a soft cloth soaked in a 0.25% chlorhexidine solution within the first hours after delivery. Control group infants will be wiped with a similar cloth containing no antimicrobial. All mothers in the study will receive tetanus toxoid during pregnancy and a clean birthing kit. Within each of these two groups, sectors will be further randomized to the three umbilical cord care arms. All groups will receive educational messages regarding hygienic cord care practices for the newborn. All children will be followed intensively for the first 2 weeks and then weekly until 4 weeks of age at which time they will be discharged. The sample size required for the study is 6744 live births per wash group, or 13500 total live births. Assuming a Type I error of 5% and a power of 80%), approximately two years of recruitment will provide adequate numbers to detect a 20% reduction in neonatal mortality. The umbilical cord infection trial will require only one year of recruitment to obtain adequate numbers to detect a 20% in infection rates in the treatment groups. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •

Project Title: NON-INVASIVE DELIVERY OF SKIN-TARGETED TETANUS VACCINES Principal Investigator & Institution: Tang, De-Chu C.; Vaxin Inc. 500 Beacon Pky W Birmingham, Al 352093108 Timing: Fiscal Year 2001; Project Start 01-MAY-1999; Project End 31-MAY-2003 Summary: (Adapted from Applicant's Abstract) A major limitation with the contemporary vaccination program as a preventative measure against tetanus is the encumbrance associated with multiple needle-dependent injections. Our aim is to develop a simple method for the delivery of tetanus vaccines by topical application of an adenovirus-vectored vaccine patch. The hypothesis is that the expression of the tetanus toxin C-fragment (tetC) in the outer layer of skin can induce a systemic immune response against the toxin molecule. We have demonstrated that a protective immune response against live Clostridium tetani infection could be elicited in mice by a single topical application of a patch containing an adenovirus vector encoding tetC. These studies will further develop the vectored vaccine patch, and specifically determine whether this novel approach for the delivery of vaccines can mobilize the immune repertoire against tetanus in humans. In this project, the potential for a vectored vaccine patch to elicit a protective immune response against tetanus in animals with preexisting immunity to adenovirus will be investigated. A new generation of adenovirus vectors with reduced immunogenicity as well as enhanced transduction efficiency for the outer layer of skin will be developed as novel vaccine carriers. Efficacy of NIVS will

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be compared to those induced by other means. The interaction between vectors and the host will be studied by determining the fate of vector DNA. A Phase I human clinical trial for evaluating the safety of a vectored vaccine patch will be conducted. The overall goal of these experiments is to determine whether tetanus vaccines can be effectively and safely delivered by a skin patch that requires a lower level of skill in a needle-free manner. PROPOSED COMMERCIAL APPLICATION: Non-invasive vaccination onto the skin may boost vaccine coverage against tetanus because the procedure is simple, effective, painless, and safe, The development may also make vaccination programs less dependent upon medical resources. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •

Project Title: OXIDATIVE NEURODEGENERATION

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Principal Investigator & Institution: Brown, Robert H.; Professor; Massachusetts General Hospital 55 Fruit St Boston, Ma 02114 Timing: Fiscal Year 2001; Project Start 15-APR-1995; Project End 31-AUG-2005 Summary: This is a proposal to investigate the hypothesis that excitotoxic and oxidative cellular pathology accumulates in the brain and spinal cord during normal aging and is accentuated in age-dependent neurodegenerative disorders. The program is a continuation of our current program project, incorporating the themes of the original program and including a genetics component involving ALS with frontotemporal dementia (ALS-FTD). Project (1) will use genetic linkage analysis to identify gene defects that cause ALS-FTD. The project will also analyze the brain of spinal cords of ALS-FTD patients for patterns of oxidative injury and correlate these with the genetic data. Hypotheses: it will be possible to use contemporary human genetics to identify one or more ALS-FTD genes loci; ALS-FTD tissues will have heightened indices of oxidative toxicity. Project (2) will quantitate oxidative damage to DNA in tissues and fluids of ALS patients and determine how these vary with the illness. Parallel aims are to analyze mitochondrial DNA for mutations in neurodegenerative disorders and test the prediction that augmenting cellular energy production will slow motor neuron death in ALS mice. Hypothesis: there is an integral relationship between mitochondrial function and energy generation and the susceptibility of the brain to oxidative insults. Project (3) will use human brain tissue and a powerful system for culturing human astrocytes to investigate mechanisms whereby excitatory and oxidative stress impair normal mRNA splicing. Hypothesis: in tissues undergoing neurodegeneration defects in mRNA splicing apparatus lead to aberrant transcript splicing, altered RNA trafficking and reduced neuronal survival. Project (4) will develop and characterize a novel fusion protein composed of tetanus C and a glutamate inactivating enzyme, glutamate pyruvate transaminase (GPT). Hypothesis: tetanus C fragment will concentrate GPT at synapses and thereby reduce ambient glutamate levels and associated excitotoxicity. The project will have three cores: (1) administration and statistics; (2) molecular genetics, to test for mutations in key genes such as SOD1 or tau, and to prepare the fusion proteins for Project 4, (3) histochemistiy, to characterize panels of markers in the neural tissues of these patients. Significance: (1) Insights into the molecular causes of ALS FTD will illuminate the pathobiology of both ALS and FTD. (2) This will be one of the first comprehensive studies of mtDNA in neurodegenerative diseases, allowing direct comparisons between sequence variants in mtDNA and markers of oxidative injury. (3) These will also be among the first studies to study aberrant RNA splicing in neurons. (4) The TTC-GPT protein is a novel concept in protein delivery with potential application to many potentially neuroprotective proteins.

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

Project Title: PHYSICAL ACTIVITY, AGING AND IMMUNE FUNCTION Principal Investigator & Institution: Woods, Jeffrey A.; Associate Professor; Kinesiology; University of Illinois Urbana-Champaign Henry Administration Bldg Champaign, Il 61820 Timing: Fiscal Year 2002; Project Start 01-MAY-2002; Project End 30-APR-2006 Summary: The extent to which exercise training or long-term physical activity influences dysregulated immune function in the elderly is unclear. Preliminary evidence suggests that exercise training may improve various dysregulated immune function measures in older adults. Although such findings have the potential to be of substantial public health importance, the majority of studies have suffered from small sample sizes, inadequate measurement of physical fitness, and weak research designs.The proposed study is designed to overcome these limitations by employing a longitudinal randomized controlled trial examining the effect of exercise training on clinically relevant immune function measures in older adults (65-80 years). Moreover, relationships between several factors known to be altered by exercise training and changes in immune function will be assessed. As such, there are two specific aims to be addressed. In Aim 1, a one-year exercise trial is proposed to determine whether moderate intensity aerobic exercise training can improve immune function in previously sedentary older adults. In Aim 2, the role played by physiological, behavioral, and psychosocial factors in the relationship between exercise training and improved immune function will be examined. Employing a randomized controlled trial, sedentary subjects (n=150) will be randomly assigned to either a one year moderate aerobic exercise training program (n = 75) or a sedentary control group (n = 75). Clinically relevant measures of immune function including the delayed-type hypersensitivity response to a battery of antigens and the antibody response to tetanus toxoid and influenza virus vaccination will be assessed before, during and after the intervention. We hypothesize that exercise training will result in improved immune responses including higher peak antibody titers and DTH responses, and sustained levels of protective antibodies. State-of-the-art analytical methods using multiple imputation and latent growth curve analyses will allow us to determine the growth and form of immune function parameters over the study period and the relative role played by physiological, behavioral, and psychosocial variables in this growth. Findings from the proposed study will help determine the role played by exercise training in immune functioning in the elderly thereby providing important empirical evidence to substantiate the prescription of exercise to combat disease and dysfunction. The public health yield of such information is likely to be substantial. In addition, the biobehavioral approach inherent in our aims will allow us to determine the complexity of the relationship between exercise and immune function. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen

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Project Title: PRESYNAPTIC REGULATION OF DENDRITE DEVELOPMENT Principal Investigator & Institution: Wong, Rachel O.; Associate Professor; Washington University Lindell and Skinker Blvd St. Louis, Mo 63130 Timing: Fiscal Year 2001 Summary: Our broad goal is to understand how precise patterns of neuronal connections are established during development of the central nervous system. This proposal focuses on the role of presynaptic signaling in organizing in organizing the structure of the postsynaptic substrate, the dendritic arbor, during synapse formation

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and refinement of the retina. The dendrites of immature retinal ganglion cells (RGCs) undergo structural and functional remodeling as they contact and receive input from presynaptic cells. The role of activity-dependent and activity- independent signaling from two classes of retinal interneurons (cholinergic amacrine cells and bipolar cells) in the remodeling of RGC arbors will be investigated. Aim 1 will characterize the structural and potential functional relationship between the terminal processes of the retinal interneurons and the dendrites of RGCs before and during RGC dendritic remodeling. RGC arbors will be labeled with multicolors by a novel method of delivering carbocyanine dyes to retinal explants (collaboration with Jeff Lichtman). Cholinergic amacrines and a subset of bipolar cells will be labeled by introducing yellow fluorescent protein downstream of promoters specific to these cells, using knock-in technology. Aims 2 and 3 will assess the in vivo roles of presynaptic signaling by ablating these interneurons or blocking their release of neurotransmitter. Transmission will be blocked by knocking out the choline acetyltransferase gene, or by introducing the tetanus toxoid (TeTx) gene downstream of the cell-specific promoters. Ablation of cells will be carried out by replacing the TeTx gene with the diptheria toxin gene. Cre-lox technology will e used to ensure that gene or cell ablation and neurotransmission blockade occurs only when induced at an appropriate developmental stage. RGC arbors from wildtype and mutant mice will be reconstructed and compared. All transgenic mice will be generated in collaboration with Josh Sanes. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •

Project Title: PROSTATE CANCER IMMUNOTHERAPY Principal Investigator & Institution: Darnell, Robert B.; Profssor; Lab/Molecular Neurooncology; Rockefeller University New York, Ny 100216399 Timing: Fiscal Year 2003; Project Start 05-JUN-2003; Project End 31-MAY-2008 Summary: (provided by applicant): Prostate cancers that have spread beyond the confines of the gland regress following the withdrawal or blockade of androgens, and at relapse, following chemotherapy. In both settings the outcomes are similar: most cells undergo growth arrest, but only few undergo apoptotic death. We hypothesize that an immune based approach can eliminate the non-proliferating yet viable cells, particularly after tumor mass has been de-bulked. Prostate cancer offers several advantages in testing new tumor immunotherapies. Serum prostate specific antigen (PSA) levels provide a simple, yet excellent marker of response to therapy. Patients with rising PSA, who have a poor prognosis, can be identified while they are still functionally healthy. As elimination of growth-arrested cells is essential in such patients, they are ideally suited for tumor immunotherapy. Our objective is to demonstrate that immunization of prostate cancer patients with autologous dendritic cells (DC's) cross-presenting apoptotic prostate tumor cells safely induces cytolytic T cell responses to tumor antigens. We will establish a system for the detection of tumor-specific T cell responses in prostate cancer patients that parallels methods established in our laboratory for influenza-specific T cell responses in normal individuals. Apoptotic prostate tumor cells will be co-cultured with DC's, allowing uptake and presentation of multiple tumor antigens on all MHC I molecules. These DC's will then be used to immunize patients. We will monitor patients for acute toxicity and T cell responses to established (e.g. prostate-specific membrane antigen) and new marker antigens present in the apoptotic prostate tumor cells to determine activity of our immunization. Our immunization method and key assays for antigen-specific T cell response are independent of patient HLA haplotype, allowing patients of all haplotype to enter the study. Our strategy is distinct in the breadth of antigen presented and potency resulting from use of the cross-

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priming pathway--up to 10,000 times more efficient than peptide pulsed DCs. Our results should indicate whether this new approach to DC based, immunotherapy has a potential role in the treatment of prostatic cancer as well as other malignancies. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •

Project Title: REAL TIME ANALYSIS OF TOXIN RECEPTOR INTERACTIONS FOR BIOSENSOR APPLICATIONS Principal Investigator & Institution: Nolan, John P.; Director; University of Calif-Los Alamos Nat Lab Ms G758 Los Alamos, Nm 87545 Timing: Fiscal Year 2001; Project Start 01-JUL-2001; Project End 30-JUN-2002 Summary: We will meet the need for a fundamentally new method of detection for biotoxin agents. Our strategy is based on using the cell surface receptor targeted by biological toxins or pathogens as the core of the sensor. Receptor-cell membrane mimics will be generated using self-assembly techniques where monolayers and bilayers are bound directly to an optical transducer surface. In addition, advanced transduction techniques that mimic the ability of natural systems to amplify signals will be developed. Our ultimate target is sensor arrays based on multiple receptor-cell membrane mimics that can serve as a "smart" sensing system capable of rapid identification and quantification of a wide range of biological toxins. Many toxins and pathogens enter cells through a general mechanism that begins with their binding of receptors on the animal cell surface. Most of the primary receptors have been identified for biological agent toxins, many of them have been identified f or bacterial pathogens, and some of them have been identified for viral pathogens. While cholera toxin was chosen for initial studies because of its experimental accessibility, ganglioside binding is a common feature of bacterial toxins. For example, the toxins from tetanus, botulinum, perfringens, and shiga and the toxin ricin all bind gangliosides before entering the cell. Thus, everything we learn about cholera toxin will be directly applicable to developing sensors for other important toxins such as botulinum and ricin. We have established two systems for detecting cholera toxin binding to its glycolipid receptor; one based on fluorescence detection by flow cytometry, and the other based on mass detection by surface plasmon resonance. In both cases the receptor is embedded in a biomimetic surface and toxin binding to the surface is detected. In flow cytometry (FC), the surface is a microsphere and the toxin is labeled with a fluorescent probe, whereas for surface plasmon reso nance (SPR), a gold-coated planar surface is used and toxin bnding is detected as a change in refractive index at the surface. These two systems represent our first generation of toxin sensors and will provide platforms with which we will optimize molecular recognition, the biomimetic substrate, and detection of binding. Systematic investigation of the receptor and toxin concentration dependence of these kinetics is in progress and will be interpreted in terms of a rigorous kinetic model to determine the individual rate constants (binding affinities) for the mixed, mono,-and multivalent binding events we envision. We will investigate the effect of receptor immobilization and of various biomimetic substrates on this interaction. These results will be used to guide the design of sensor surfaces with the desired sensitivity, specificity, reversibility, and stability. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen

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Project Title: RECOMBINANT & LIVE ORAL SALMONELLA TYPHI HYBRID VACCINES Principal Investigator & Institution: Levine, Myron M.; Director, Ctr for Vaccine Development; Medicine; University of Maryland Balt Prof School Baltimore, Md 21201

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Timing: Fiscal Year 2001; Project Start 01-APR-1990; Project End 31-MAR-2003 Summary: (Adapted from the applicant's abstract): The overall goal of the proposed research is to develop, through appropriate manipulations of a suitable attenuated Salmonella typhi live vector, a mucosally-administered multivalent vaccine to prevent diphtheria, pertussis, and tetanus (i.e., a mucosal DTP vaccine). To accomplish this, the PI will initially successfully express within attenuate S. typhi appropriate protective antigens from C. diphtheriae, B. pertussis, and C. tetani and confirm, using the murine intranasal model of immunogenicity, that such constructs elicit the relevant types of immune responses. The PI and his colleagues will then attempt to improve such immune responses in several ways: (1) relevant proteins will be expressed in attenuated S. typhi strains in which expression of the Vi capsular polysaccharide has either been removed or expression has been made constitutive. (2) A fusion protein consisting of fragment C of tetanus toxin fused to the truncated S1 subunit of pertussis toxin, used as a test antigen, will be secreted extracellularly using the E. coli hemolysin and secretion apparatus. (3) Proteins will be expressed from stabilized plasmids which encode a critical enzyme necessary for survival of the attenuated S. typhi carrier strain. (4) The fragment C-S1 fusion protein will be expressed in S. typhi live vector strains which will co-express either a mutant heat-labile enterotoxin of E. coli (the K63 LT holotoxoid) that functions as a powerful adjuvant yet does not cause intestinal secretion or will coexpress the IL-4 cytokine (which has the effect of enhancing antibody responses). The PI and his colleagues will make amino acid substitutions in the NAD-binding region of diphtheria toxin, aiming to construct a stable mutant that lacks enzymatic (i.e., toxic) activity, but retains the ability to stimulate neutralizing antitoxin. It is expected that by the end of the research plan, all the individual constructs necessary to stimulate protective immune responses will have been constructed, their immunogenicity established in the mouse intranasal immunization model and modifications selected to enhance the specific immune responses. This will set the stage for a future effort that would examine the immunogenicity of a prototype multivalent DTP vaccine consisting of a mixture of the optimized CVD908-htrA constructs expressing diphtheria, pertussis and tetanus antigens. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •

Project Title: REDUCING DISPARITIES IN CLINICAL PREVENTIVE SERVICES Principal Investigator & Institution: Wallace, Steven P.; Associate Professor; University of California Los Angeles 10920 Wilshire Blvd., Suite 1200 Los Angeles, Ca 90024 Timing: Fiscal Year 2001 Summary: Racial disparities exist for a number of clinical preventive services for which scientific evidence documents improved morbidity and mortality outcomes as a result of their use (routine childhood immunizations, tetanus and flu/pneumonia immunizations, mammography, cholesterol screening, having a regular source of care, routine oral exams, sigmoidoscopy, and colonoscopy). To improve our ability to design cost- effective interventions to increase the appropriate use of clinical preventive services by members of racial and ethnic minority groups, we will: 1. Analyze the individual and contextual predictors of clinical preventive service use by racial and ethnic minorities to determine the extent to which disparities exist. 2. Compare the effects of these predictors using logistic regression across (a) different racial and ethnic groups to identify how differences result from (i) differences in population characteristics and/or (ii) differences in the effects of predictors across population AND (b) compare effects of these predictors across different clinical preventive services to identify common mutable factors. 3. Drawing on existing estimates from the literature of

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preventive services' health status improvements, the parameter estimates developed above, and "best estimate" costs of modifying each factor, conduct Monte Carlo simulations of the relative merits of different interventions. 4. Design and solicit additional funding for at least one intervention trial that would address a cross-cutting determinant of clinical preventive service disparities identified above. Analyses will be conducted using the MEPS, MCBS, NHIS, and California Health Interview Survey. The first two datasets provide extensive detail on independent variables with smaller sample sizes and fewer dependent variables. The latter datasets contain extensive detail on dependent variables with some loss of detail on independent variables. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •

Project Title: REGULATING ANTIGEN PRESENTATION BY HUMAN FEMALE REPRODUCTIVE TRACT CELLS Principal Investigator & Institution: Wira, Charles R.; Professor of Physiology; Dartmouth College 11 Rope Ferry Rd. #6210 Hanover, Nh 03755 Timing: Fiscal Year 2001 Summary: The female reproductive tract (FRT) is a unique system that must be protected from infection by pathogens, yet must also accept allogeneic spermatozoa and conceptuses. Thus, unlike their peripheral blood counterparts, immune cells within the FRT are influenced by sex hormones in a manner consistent with these dual functions. Our studies in both the human and rat have demonstrated that sex hormones have profound effects on T cell activation by FRT antigen presenting cells (APC), and provide the foundation for the current proposal, which is designed to test the hypothesis that the inductive arm of the immune system is hormonally regulated within the human FRT. Questions to be addressed are: (1) Can human FRT epithelial cells present antigens?; (2) How do epithelial cell- leukocyte interactions modulate T cell activation?; (3) By what mechanism(s) does endocrine balance modulate antigen presentation?; and (4) Does Fc receptor targeting enhance antigen presentation by FRT cells? We will isolate pure populations of epithelial cells and professional APC from each FRT tissue and characterize their efficiency of antigen presentation in response to antigen (tetanus toxoid; defined peptides; allogeneic APC) and polyclonal T cell activators (anti-CD3; bacterial super-antigen). We will then determine how epithelial and stromal cell populations modulate professional APC (macrophages and dendritic cells) phenotype, maturation, and efficiency for T cell activation, and will use blocking antibodies and soluble receptors to evaluate the cytokines and signaling molecules that influence T cell activation by APC. We will also examine how sex hormones and cytokines, which fluctuate during the menstrual cycle, alter the phenotype or function of APC either directly or via effects on stromal and epithelial cell populations. Finally, based on observations that T cell activation is markedly enhanced by targeting antigen to Fc receptors, we will determine the FRT APC for which IgG- and IgA-receptor targeting enhances antigen presentation, as well as the effects of cytokines and sex hormones on this pathway. These studies will thus result in the systematic analysis of the identity and antigen presenting efficiency of APC populations naturally present at each of the different human FRT tissue sites. Thus, we will investigate mechanisms including processing, presentation, and provision of co- stimulatory signals and cytokines necessary for T cell activation, leading to an understanding of how sex hormones and cytokines act, either directly on APC or through effects on nearby cells, to increase or decrease APC function. Overall, these studies should significantly increase our knowledge about the hormonal influences on induction and/or suppression of immune

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responses in this critical organ system, and lay the foundation for developing realistic approaches to the development of vaccines for sexually transmitted diseases. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •

Project Title: REGULATION OF ADRENAL FUNCTION IN FIBROMYALGIA Principal Investigator & Institution: Adler, Gail K.; Assistant Professor; Brigham and Women's Hospital 75 Francis Street Boston, Ma 02115 Timing: Fiscal Year 2001; Project Start 25-SEP-1994; Project End 31-JUL-2003 Summary: (Adapted From Applicant's Abstract) This competitive renewal project proposes to extend studies of the hypothalamic-pituitary-adrenal axis in fibromyalgia syndrome previously undertaken by the PI. Her initial data suggested reduced adrenocorticotropin (ACTH) and epinephrine responses to graded hypoglycemic challenge, and blunting of the normal diurnal cortisol rhythm in patients with fibromyalgia when compared to normal controls. The PI postulates that the decreased ACTH response to hypoglycemic challenge is the result of impaired CRH release, this also results in decreased sympathoadrenal response to hypoglycemia. The PI further proposes that the diurnal cortisol rhythm in patients with fibromyalgia is abnormal due to a shift in the circadian phase. In Specific Aim 1, the PI and her colleagues propose to assess hypothalamic CRH-pituitary ACTH activity at baseline and in response to three stimuli: hypoglycemia, metapyrone-induced glucocorticoid administration, and an immune stimulus with tetanus toxoid vaccine. In Specific Aim 2, sypathoadrenal responses to hypoglycemia, the cold pressor test, metapyrone vs. placebo will be compared in patients with fibromyalgia and controls. In Specific Aim 3, the circadian phase (measured by core body temperature and melatonin levels) will be compared in women with fibromyalgia and healthy controls. Additional studies of the relationship between disrupted sleep pattern and night-time secretion of ACTH and cortisol and cytokines are planned if the circadian phase is not shifted. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen

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Project Title: REGULATION OF HIPPOCAMPAL SYNAPSE DEVELOPMENT-DYNAMICS Principal Investigator & Institution: Craig, Ann M.; Associate Professor; Washington University Lindell and Skinker Blvd St. Louis, Mo 63130 Timing: Fiscal Year 2001 Summary: The long term goal of this research is to understand from a cellular and molecular perspective how specialized synaptic sites are generated, maintained and regulated between central neurons. Hippocampal neurons in low density culture provide an accessible model system to study excitatory glutamatergic and inhibitory GABAergic synapse development. The focus of this proposal is to use novel molecular, genetic and imagining tools to address two major issues: synapse dynamics and mechanisms of initiation; and cellular and molecular mechanisms of synaptic competition. Aim 1 will define changes in synapse stability with maturation by live imaging of synaptophysin-Cyan Fluorescent Protein and post-synaptic density protein PSD95-Yellow Fluorescent Protein. Aim 2 will combined these methods with fluorescent dye labeling of neuronal structure to determine the roles of axonal and dendritic filopodia in synapse initiation, as well as begin to test potential cell adhesion and kinase signaling mechanisms underlying synapse initiation. In Aims 3 and 4, model systems of hippocampal neurons in culture fostering synapse formation in environments of competitive activity will be generated, where the activity status of each pre- and post-

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synaptic element is known and the effects on arbor outgrowth and synapse formation and stability determined. Transmitter release or response will be manipulated by expression of tetanus toxin or dominant negative AMPA or NMDA type glutamate receptors or by genetic knockout of the GABA receptor anchoring protein gephyrin in subsets of neurons. These studies represent attacks of fundamental issues in developmental neurobiology generated through intellectual and practical interactions with Josh Sanes, Jeff Lichtman and Rachel Wong. The studies of mechanisms of synapse initiation (Aims 1-2) will lead toward promoting regeneration of connections after neurological insult and the studies of synaptic competition (Aims 3-4) will help to understand how early experience in infancy and childhood shape the connectivity of pathways in the brain. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •

Project Title: REGULATION OF NEUROTRANSMITTER RELEASE BY RAB GTPASES Principal Investigator & Institution: Engisch, Kathrin L.; Physiology; Emory University 1784 North Decatur Road Atlanta, Ga 30322 Timing: Fiscal Year 2002; Project Start 13-FEB-2002; Project End 31-JAN-2006 Summary: (provided by applicant): The release of neurotransmitters from a nerve terminal occurs by fusion of membrane-bound vesicles with the presynaptic membrane, and dispersion of the vesicle contents into the extracellular space. We are rapidly gaining a molecular understanding of vesicle fusion, based on studies of vesicle trafficking between intracellular compartments, such as the endoplasmic reticulum and the golgi apparatus. The proteins that comprise the minimum fusion machinery have been identified, and neuronal isoforms of these proteins are essential for transmitter release. They are targets of the botulinum and tetanus toxins, neurotoxins that severely impair transmitter release at the neuromuscular junction and at inhibitory synapses in the brain, respectively. Thus synaptic vesicle fusion is a form of vesicle trafficking that is no longer unregulated - it requires a signal: calcium ions. The more calcium ions that enter the nerve terminal, the greater the amount of transmitter release. Transmitter release can be modulated by activity. Depending on experimental conditions and the synapse being studied, rapid repetitive stimulation can increase the amount of transmitter released by each stimulus (facilitation), or there can be a reduction in release with each successive impulse (depression). We do not yet understand how the basic fusion machinery is able to respond so differently to large vs. small levels of calcium influx: and to be modulated up, or down, by prior activity. Rab GTPases are a family of proteins with specific members located at each step along the pathway of intracellular membrane trafficking. Biochemical evidence suggests that rab GTPases promote the formation of the basic fusion machinery - facilitating the pairing between proteins on the vesicle and those on the target membrane. Rab3a, the rab GTPase located on synaptic vesicles, is a likely candidate for a regulator of the synaptic vesicle fusion machinery, and thus, transmitter release. In this proposal we examine transmitter release at the neuromuscular junction and in adrenal chromaffin cells expressing different levels of rab3a or a constituitively activated rab3a mutant, rab3a [Q81L], to determine if the rab3a GTPase is a modulator of transmitter release. The results of these studies will increase our ability to alter the amount of transmitter release in neurological diseases in which transmitter release is abnormal. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen

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Project Title: RETARGETING HSV-1 VECTORS TO MOTOR NEURONS Principal Investigator & Institution: Glorioso, Joseph C.; Professor and Chairman; Molecular Genetics & Biochem; University of Pittsburgh at Pittsburgh 350 Thackeray Hall Pittsburgh, Pa 15260 Timing: Fiscal Year 2002; Project Start 03-JUL-2002; Project End 30-JUN-2006 Summary: (provided by applicant) A variety of diseases affect the viability and function of motor neurons located within the spinal cord and projecting to muscle throughout the body. In order to develop an effective gene therapy application to treat MN disease it will be necessary to efficiently transduce MNs in vivo. Herpes simplex virus type 1 (HSV-1) has been engineered to be a versatile gene vector for transduction of sensory nerves in vivo, the natural site for wild-type virus latency. While high multiplicity infection of spinal cord will result in virus transduction of motor neurons (MNs), replication defective HSV vectors fail to transduce motor neurons in adult rodent models following skin or muscle inoculation. A similar result is likely to occur in human gene therapy applications since HSV is not found in MNs in natural infections. Thus treatment of MN diseases will require the enhancement of HSV vector infection of MNs with the longer-range goal of limiting the virus host-range to MN receptors. Because little is known about the effects of introducing new receptor binding ligands into the HSV-1 envelope, the applicants will explore strategies to enhance and eventually retarget HSV infection to MNs through modification of the receptor binding activities of three fundamentally different envelope components, glycoproteins B, C, and D. Because tetanus toxin receptors (TTR) are specifically found on MN synaptic junctions, we will focus our efforts on using nontoxic TTR binding components of the tetanus toxin engineered to be presented on the virus envelope as recombinant glycoproteins capable of initiating virus attachment and entry into MNs both in vitro and in vivo. Aim 1 is designed to target HSV to MNs by substitution of the native heparan sulfate attachment determinants presented by HSV glycoproteins B and C (gB and gC) with a tetanus toxin (TTx) heavy chain C-terminal fragment (HcC). Aim 2 is intended to restrict virus infection via HveB binding and evaluate re-targeting of gD via HcC. Aim 3 is designed to test soluble HveC in combination with HcC ligand bearing gC and gB or HveC-HcC soluble fusion proteins as effectors of MN targeting. The soluble HveC adapter will be expected to block gD binding to cellular HveC while directly or indirectly re-targeting the virus to TTx receptors. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen

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Project Title: RETINOID NUTRITIONAL STATUS AND IMMUNE FUNCTION Principal Investigator & Institution: Ross, a C.; Professor; Nutritional Sciences; Pennsylvania State University-Univ Park 201 Old Main University Park, Pa 16802 Timing: Fiscal Year 2002; Project Start 01-APR-1989; Project End 31-AUG-2002 Summary: Vitamin A deficiency increases the risk of childhood mortality, presumably due to poor immune responses to infectious diseases. Using well controlled animal models, we have shown that the antibody response to immunization is particularly low against T cell-dependent (TD) and T cell-independent type 2 antigens. Nonetheless, vitamin A-deficient animals can produce strong antibody responses to these antigens, even above normal levels, when treated with agents including retinoids, lipopolysaccharide (LPS), tumor necrosis factor (TNF)-alpha, or the double-stranded RNA, poly(I:C), a known inducer of interferons (IFNs). Other cell biological and clinical research supports a positive synergistic interaction of retinoids and cytokines-including TNF and IFNs-in inhibiting tumor cell growth. Thus, we propose to investigate retinoid-

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cytokine interactions in the immune system, utilizing vitamin A-deficient, control, retinoid-repleted, and transgenic mice as models. Experiments are designed to understand how TNF, hype I and type II IFNs, and cytokine inducers retinoids, monophosphoryl lipid A (MPL), or poly(I:C)-Iysine carboxymethylcellulose] amplify antigen-specific responses to TD and type 2 antigens (exemplified by tetanus toxoid and pneumococcal polysaccharide, respectively, in our studies). We will test the hypothesis that these agents increase the expression of interleukin (IL)-12, a cytokine with broad immunoregulatory activity; the IL-2 receptor, an immediate early gene; and STAT1, a member of the Signal Transducers and Activators of Transcription family of postreceptor factors that transduce signaling for type I and type II IFNs. By investigating the quantitative and qualitative characteristics of antigen-specific and non-specific immune responses following treatment with retinoids and adjuvants, we hope to improve the mechanistic understanding of retinoid-cytokine interactions, and to elucidate the potential of nutritional and adjuvant strategies to enhance immunity in immunocompromised hosts. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •

Project Title: ROLE OF SUPERANTIGENS IN TREATMENT OF RHEUMATOID ARTHRITIS Principal Investigator & Institution: Cannon, Grant W.; University of Utah Salt Lake City, Ut 84102 Timing: Fiscal Year 2001 Summary: This project has now been completed. Twenty-three patients were enrolled at the University of Utah, with a total of 240 patients participating at twelve other sites across the nation. Although part of a multicenter trial, a specific hypothesis was tested by investigators at the University of Utah. Dr. Cannon doubted that immune complex absorption represented the mechanism by which protein A absorption exerted its therapeutic effect. An alternate hypothesis was proposed, stating that patients treated with protein A-perfused plasma developed immune responses to staphylococcal proteins leached from the column, which then altered immune responses to rheumatoid arthritis. The putative staphylococcal proteins were predicted to function as super antigens. Testing of the counter hypothesis was deemed an appropriate indication to make this a category A study by the GCRC Advisory Committee. The study has now been completed, and a preliminary analysis supports the hypothesis. A publication will be prepared describing the findings within the next year. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen

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Project Title: SENESCENCE AND STRIATAL SYNAPTIC PLASTICITY Principal Investigator & Institution: Walsh, John P.; Neurogerontology; University of Southern California 2250 Alcazar Street, Csc-219 Los Angeles, Ca 90033 Timing: Fiscal Year 2001; Project Start 10-AUG-1995; Project End 31-DEC-2001 Summary: The influence of age on long-term synaptic plasticity will be studied int he striatum using in vitro brain slice and intracellular recording techniques. Synaptic efficacy will be monitored by sampling responses to paired stimuli. This procedure allows simultaneous monitoring of short- term, presynaptic changes in release and longterm tetanus induced changes in synaptic efficacy. Correlations will then be performed between paired- pulse and long -term synaptic plasticity. Each hypothesis will be tested under conditions that increase the probability of inducing LTD and, in a separate set of experiments, LTP. Initially the effect of senescence will be established for LTD and LTP.

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The second specific aim will then test the hypotheses that 1) inrinsic dopamine (DA) released in in vitro slices modulates synaptic plasticity in the striatum, and 2) that this modulation declines with age. DA will be depleted through unilateral 6-OHDA lesions to the substantia nigra (SNc). Lesion effects will be determined through comparisons to the contralateral (DA intact) striatum. DAergic modulation of synaptic plasticity will then be studied DA perfusion of slices ipsilateral to the 6-OHDA lesion. Since intrinsic release will be eliminated in these slices, dose-response comparisons can be made between age-groups. This procedure thus allows us to test the hypothesis that agedependent differences in DA receptor activation alter DA modulation of synaptic plasticity. DA depletion will be quantified by calculating loss of tyrosine hydroxylase positive neurons in the SNc and measurements of DA content int he striatum (HPLC). The third specific aim will test the hypotheses that 1) long-term synaptic plasticity is triggered by tetanus induced transients in intracellular Ca2+ and that 2) this process is altered by age-related changes in Ca2+ homeostasis. Two complementary procedures will be used to differentiate between the role of pre- and postsynaptic fluxes of Ca2+. First, brain slices will be exposed to a low Ca2+ solution that will reduce Ca2+ influx uniformly in pre-and postsynaptic compartments. These result will be compared with 1) data from slices bathed in normal Ca2+ and 2) data obtained when only postsynaptic Ca2+ is lowered through intracellular injection of BAPTA. The fourth specific aim will determine if synaptic plasticity int he striatum is related to cell classification and location in the calbindin D28K defined 3-dimensional patch-matrix system. The final goal of this proposal will be to determine if age-related alterations in motor performance are correlated with underlying deficits in striatal synaptic plasticity. In total, these studies will provide a novel electrophysiological framework for interpreting basal ganglia-related changes in motor performance in aging. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •

Project Title: STCE, AN E.COLI O157:H7 PROTEASE SPECIFIC FOR C1-INH Principal Investigator & Institution: Welch, Rodney A.; Professor & Chair; Medical Microbiol & Immunology; University of Wisconsin Madison 750 University Ave Madison, Wi 53706 Timing: Fiscal Year 2003; Project Start 16-JAN-2003; Project End 31-DEC-2007 Summary: (Provided by applicant): Enterohemorrhagic Escherichia coli (EHEC), principally serotype O157:H7, cause an estimated 20,000 cases of diarrheal disease in the United States per year. 2-6 percent of the infected individuals, mostly young children progress to a severe renal disease, hemolytic uremic syndrome (HUS). The EHEC pathogenic factors that lead to bloody colitis and HUS are poorly understood, but knowledge of some mechanisms has recently emerged. Intimin-mediated adherence and type III effectors are encoded by a chromosomal locus termed LEE. The phage-encoded Shiga toxins (Stxs) are responsible for significant aspects of EHEC disease. EHEC strains commonly possess large plasmids, the prototype being pO157. We have identified a new pO157 gene, stcE, which encodes an extracellular zinc-metalloendoprotease (ZMP) that specifically cleaves the critical anti-inflammatory regulator C l-esterase inhibitor (C 1-Inh). C 1-Inh is a serine protease inhibitor (serpin) that provides the principal inhibition of the proteolytic cascades involved in classic and mannan-binding ligand complement activation, contact activation and intrinsic coagulation. C l-Inh inhibits diverse proteases: Clr and Cls, MASP-1, MASP-2, kallikrein, FXIIa, FXIa, and plasmin. Deficiencies in Cl-Inh cause profound clinical syndromes. The best known is hereditary angioedema (HAE), a genetic deficiency in Cl-Inh, which is characterized by transient, recurrent attacks of intestinal cramps, vomiting, diarrhea and life-threatening episodes

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of tracheal swelling. Fluorescenated StcE binds to cultured macrophages, B- and T-cells. Thus, StcE is an example of a growing class of ZMPs such as tetanus, botulinum and anthrax lethal factor toxins. These ZMPs, in contrast to the homologous Pseudomonas and Vibrio ZMPs, have specific, non-extracellular matrix protein targets. We will test the hypothesis that StcE degrades soluble or cell-associated Cl-Inh, and this results in poorly regulated serine protease cascades involving complement activation, contact activation and coagulation. This dysregulation would then contribute to local inflammation, tissue damage and edema. The elucidation of StcE structure and function(s) may result in new targets for chemotherapeutic or immune prevention or treatment of EHEC infections, which now are best managed only by supportive therapy. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •

Project Title: SYMPTOM AND EMOTION STIMULI TO HEALTH ACTION IN ELDERLY Principal Investigator & Institution: Leventhal, Howard; Professor O Psychology; None; Rutgers the St Univ of Nj New Brunswick Asb Iii New Brunswick, Nj 08901 Timing: Fiscal Year 1999; Project Start 01-SEP-1982; Project End 30-JUN-2004 Summary: It has recently been claimed that symptom reports cannot be used as indicators of disease because they are confounded by personality dispositions, e.g., the tendency to experience negative affect, a conclusion that would invalidate large bodies of data used to estimate health needs and to assess the effects of psychosocial factors, e.g., age, stressors, upon illness. Our conceptualization of symptoms as the result of the bodies immunological response to pathogens, predicts that both symptoms and immunological reactions will be less intense in older than younger persons and in depressed than non-depressed or anxious individuals. We also state that appraisal procedures intervene between symptoms and the decision that one is ill and in need of medical care, and that anxious and depressed individuals may fail to conclude they are ill and in need of health care if they attribute symptoms to their emotional states rather than illness. We also predict that depressed individuals will experience a greater number of vague, systemic symptoms rather than intense, disease specific symptoms, and that the accumulation of such episodes over a 3 year period will result in increase s in trait depression. These hypotheses will be tested in a 3 year longitudinal trial (LT) and two, smaller, embedded investigations. Four, 1&1/2 hour interviews will be conducted\at yearly intervals with 1,200 residents (ages 55 to 90) of a New Jersey retirement community. Measures of trait anxiety and depression, illness history, social support networks, life stress, preventive health behaviors, and reports of symptom episodes during the prior two weeks will be obtained at each interview. Four phone calls between the yearly intervals will tap and trak the initiation, interpretation, mode of coping and resolution of symptom episodes. A quasi experimental study will examine the symptomatic and antibody reactions to either tetanus or flu inoculation of 288 residents selected to vary on age and trait anxiety and depression. A second study examines the diurnal variation of symptom reports as a function of age and trait anxiety and depression. The complete data set should allow reasonably strong conclusions regarding the role of personality, age, preventive health actions and life stress on the formation and appraisal of symptoms. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen

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Project Title: SYNAPTIC HIPPOCAMPUS

ACTIONS

OF

OPIOID

PEPTIDES

IN

THE

Principal Investigator & Institution: Nicoll, Roger A.; Cellular and Molecular Pharmacology; University of California San Francisco 500 Parnassus Ave San Francisco, Ca 94122 Timing: Fiscal Year 2001; Project Start 15-DEC-1996; Project End 30-NOV-2002 Summary: (Applicant's Abstract) The physiological role of neuropeptides in the brain has received much attention, but we still have a rudimentary understanding of their synaptic roles. Recently we have found that the opioid peptide dynorphin is released during high-frequency stimulation from mossy fibers (mfs), and causes a presynaptic inhibition of neighboring mf synapses by acting on kappa 1 opioid receptors. It also raises the threshold for the induction of mf long-term potentiation (LTP). This grant proposes to examine 7 questions: (1) how does dynorphin inhibit transmitter release from mfs? Experiments will examine the effects of selective Ca channel blockers on the action of dynorphin as well as the effect of dynorphin on the frequency of miniature excitatory postsynaptic currents; (2) what are the properties controlling the release of dynorphin from mf synapses? We will apply AM esters of slow Ca buffers, such as EGTA, to selectively block peptide release; (3) what factors are responsible for the remarkably slow time course of the synaptically-released dynorphin? We will apply a brief puff of dynorphin and terminate the action of dynorphin by rapidly applying opioid antagonists. Application of a cocktail of peptidase inhibitors will determine if the time course is governed by enzymatic degradation; (4) are kappa 1 receptors actually present in the CA3 region? We will design experiments to localize the action of dynorphin, (5) what is the potency of the various opioid peptides that are contained in mfs? This information will help identify the most likely candidate for the synaptic effects; (6) does activation of kappa 2 receptors inhibit mf fiber evoked N-methyl-Daspartate receptor mediated responses, and if so, what is the mechanism? (7) are there similarities between our results with dynorphin at mf synapses and the possible role of enkephalins at the lateral perforant path in the dentate gyrus? We will test the hypothesis that enkephalin controls the induction of LTP at this synapse by causing disinhibition during the tetanus. These studies will involve characterizing opioid mediated synaptic effects on identified interneurons. While neuropeptides have received much attention, particularly opioid peptides, the role of this class of signaling molecule remains very unclear. The present study will help define the physiological role of neuropeptides in the CNS at the cellular level which is absolutely essential for understanding the role of these peptidergic synapses in affect, cognition, substance abuse, and the management of pain. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •

Project Title: SYNTHETIC PEPTIDE VACCINES FOR DENTAL CARIES Principal Investigator & Institution: Taubman, Martin A.; Senior Member and Head; Forsyth Institute Boston, Ma 02115 Timing: Fiscal Year 2001; Project Start 01-MAY-1996; Project End 30-JUN-2006 Summary: Our overall aim is to develop immunization constructs, vectors, and strategies which have the best chance of inducing protective immune responses to mutans streptococcal infections in susceptible pediatric populations. We have previously identified several glucosyltransferases (GTF) enzyme sequences which can induce immune response in rodents which will alter GTF activity and reduce subsequent dental caries. To enhance the induction of protective immune responses we

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will first identify sequences from glucosyltransferase (GTF) enzymes from S. mutans and S. sobrinus associated with potent Class II MHC binding in humans. Peptides based on these and on novel GTF epitopes, recently shown to influence catalytic activity and transitional state stability of the enzyme (activity associated) will be synthesized and evaluated for immunogenicity and protective effect. These epitopes, together with other functionally significant peptides derived from the catalytic and glucans binding domains of GTF previously shown to induce protective responses, well be incorporated into conjugate vaccines with tetanus toxoid (TT). Intranasal routes for mucosal immunization with TT- GTF peptide conjugate vaccine will be investigated for the ability to induce protective levels of immunity in the oral cavity in the well established rodent model of experimental dental caries. Since the intranasal route may be contraindicated in children with upper respiratory conditions such as asthma, the colorectal route of administration will also be explored using constructs combined with or without mucosal adjuvants such detoxified mutant E. coli enterotoxin (LT) or unmethylated CpG oligodinucleotides. The protective effect of systemic immunization with TT-GTF peptide conjugate vaccine studies will also be investigated as an approach to minimizing the frequency of visits required for childhood immunizations, since evidence suggests that this route of immunization can induce salivary IgA antibody in young children. Various of the mist effective peptide(s) as determined by TT-GTF peptide conjugate vaccine studies will be expressed recombinantly in attenuated Salmonella typhi vectors which can target these epitopes to appropriate mucosal inductive sites. Caries protection will be evaluated after intranasal immunization with these attenuated Salmonella vectors. Our goal is to design a vaccine that contains a combination of immunologically potent and functionally relevant epitopes, in formats, by routes, and with adjuvants that result in sustained levels of protection from dental caries and that will be acceptable for human use. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •

Project Title: TARGETED MOTOR NEURON GENE DELIVERY FOR SPASTICITY Principal Investigator & Institution: Boulis, Nicholas M.; Cleveland Clinic Foundation 9500 Euclid Ave Cleveland, Oh 44195 Timing: Fiscal Year 2002; Project Start 15-AUG-2002; Project End 31-JUL-2007 Summary: (provided by applicant): Technological advancements have provided neurosurgery with new paradigms for the restoration of neural function. The dual emergence of accurate stereotaxis and deep brain stimulation (DBS) have generated a revolution in the application of targeted neuromodulation applied to movement disorders, epilepsy, eating disorders, obsessive compulsive disease, and pain (Appendix C). Nonetheless, because DBS depends on the focused delivery of electric current, it is incapable of pharmacological specificity. Rather than delivering electric current, viral vectors can alter synaptic function with molecular specificity. Further, vector tropism can be modified, creating the potential for system specific neuronal gene delivery. The experiments outlined in this proposal attempt to develop a vector capable of both neural tropism and neuromodulation. To test these concepts, we propose to develop a recombinant adeno-associated virus (rAAV) capable of synaptic inhibition and motor neuron tropism. We have chosen the spinal reflex arc as a simple mammalian functional system amenable to neuromodulation. In addition, the functional disorder, spasticity, provides a target for the study of applied neuromodulation. We hypothesize that an rAAV vector capable of specific motor neuron inhibition will have therapeutic efficacy in animal models of spasticity. In addition to providing a novel approach to spasticity, data from these studies will permit the rational design of rAAV vector(s) for application

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to motor neuron disease (ALS) and stereotactic neuromodulation. There are 3 Aims: 1) Construct novel vectors capable of focused synaptic inhibition, 2) develop strategies for targeted gene delivery to motor neurons with rAAV, 3) apply targeted rAAV capable of synaptic inhibition in models of spasticity. The applicant has developed a focused interest in the neural basis for behavior in both normal and pathological states. His early training in simple systems neurophysiology, and later training in biochemistry and molecular biology have prepared him for a career in the study of focused gene-based neuromodulation. His appointment to the Cleveland Clinic Foundation will give him access to one of the most active programs in Functional Neurosurgery, and create opportunities for clinical application of his work. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •

Project Title: TETANUS TOXIN MONOLAYER CRYSTAL Principal Investigator & Institution: Schmid, Michael F.; Baylor College of Medicine 1 Baylor Plaza Houston, Tx 77030 Timing: Fiscal Year 2001 Summary: We have renewed our effort to pursue the structural analysis of the tetanus toxin which was grown on the phospholipid along with its natural ganglioside ligand. Our previous analysis suggested the possibility of obtaining high resolution image data beyond 10 using flood beam illumination. We plan to vary the crystallization condition to obtain more ordered two-dimensional crystals and to use spot-scan imaging to obtain better images. We feel that this project has a potential to become a core project for the development of high resolution two-dimensional crystal structure analysis in place of the crotoxin complex crystal core project which has been terminated. The significance of this project is partly to solve an unknown protein structure and partly to show the feasibility of determining the high resolution three-dimensional structure of protein crystals grown on phospholipid monolayers. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen

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Project Title: THE IMMUNOBIOLOGY OF VLA-1 ON SUBSETS OF HUMAN T CELLS Principal Investigator & Institution: Bank, Ilan; Columbia University Health Sciences New York, Ny 10032 Timing: Fiscal Year 2003; Project Start 01-SEP-2003; Project End 31-AUG-2008 Summary: The alpha1beta1 integrin (termed very late antigen-1, VLA-1) is a heterodimeric collagen receptor that becomes expressed only on primed CD45RO+ T cells and in particular on T-cells infiltrating inflamed tissues. Thus, for example, in rheumatoid arthritis (RA) patients, a large fraction of the CD4+ T cells infiltrating the inflamed synovium express VLA-1. In addition, other activated immune cells (excluding B cells) and various mesenchymal and endothelial cells express VLA-1. Recent studies in animal models of inflammation demonstrated the critical role of VLA-1 in certain immune mediated responses. Importantly, although these studies suggest a therapeutic potential for VLA-1 blockade in inflammation, the exact mechanisms involved have not been well studied. The main theme of this proposal is to study aspects of VLA- 1 biology that are unique to subsets of effector T cells. Our preliminary studies address novel aspects of VLA- 1 biology in CD4+ T cells, the subset that orchestrates most cognate immune responses. We find that VLA-1 expression in vivo is associated with T helper (TH)1 polarization. Furthermore, activating fresh unselected PBL ex vivo in the presence of TH1 (versus TH2) polarizing cytokines increases the fraction of VLA-1+ cells. In

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addition, following polyclonal activation by anti-CD3 mAbs, super-antigens, or the mixed leukocyte reaction (MLR), VLA- 1 expression is restricted only to a relatively small subset of the activated CD4+CD45RO+ cells, and lines and clones with a stable VLA-1- or VLA-1 + phenotype can be generated. In contrast re-activated memoryantigen-primed (e.g., by tetanus toxoid) CD4+ CD45RO+ T cells were highly enriched for the VLA-1+ phenotype. We therefore hypothesize that VLA-1 expression within the effector and memory CD4+ T cell population represents a functionally relevant lineage commitment. In this regard, it has already been shown that VLA-1 mediates adhesion and migration of T cells in collagenous matrices, while simultaneously inducing distinct signaling pathways that support cell cycle progression and cytokine secretion. Our specific aims are: (1) To further characterize the VLA-1 + and VLA-1- subsets with respect to: (a) co-expression patterns of additional functionally relevant markers, (b) effector functions, including: cytokine secretion, and helper, suppressor or cytotoxic capacity; (2) To further study in human autoimmunity, if the VLA-1 + phenotype is associated with functional auto-aggressive CD4+ TH1 cells and can serve as a marker to identify clonal expansions of pathogenic T cells; (3) To determine the effect of VLA-1 blockade in vivo on CD4+ TH1 cell effector functions in humans. (4) To study the effects of anti-VLA-1 immuno-therapy on functionally relevant auto-aggressive CD4+ TH1 in vivo in mouse models of experimental allergic encephalomyelitis (EAE). Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •

Project Title: THE ROLE OF P75 RECEPTOR IN TETANUS TOXIN TRANSPORT Principal Investigator & Institution: Butowt, Rafal; Physiology and Cell Biology; University of Nevada Reno Reno, Nv 89557 Timing: Fiscal Year 2004; Project Start 01-JAN-2004; Project End 31-DEC-2005 Summary: (provided by applicant): Bacterial neurotoxins (botulinum and tetanus) produced by genus Clostridium are among the most toxic natural substances known. They share many structural and functional similarities, however their sites of action within the nervous system are quite different. Botulinum toxin (BoT) is acting in the periphery, whereas tetanus toxin (TeT) acts in the central nervous system (CNS). It is believed that this phenomenon is due to high affinity binding to different specific protein receptors present at presynaptic membranes. Likely, TeT binds to a receptor which under normal conditions enters the endocytotic pathway and travels along axons while BoT does not. Despite 30 years of research on Clostridial neurotoxins this aspect of their biology remains largely unknown. No protein receptor or non-protein binding molecule has been identified to date which could explain extensive neuronal trafficking of TeT but lack of this feature for homologous BoT molecule(s). The proposed project focuses on a molecular and biochemical analysis of axonal trafficking of TeT. On the base of preliminary results and indirect data existing in the literature, it is proposed that the common neurotrophin p75 receptor may be used as a binding protein and/or axonal carrier for TeT molecules. This project includes a set of experiments to test this hypothesis. Possible interactions between TeT and p75 receptor will be examined in vitro and in vivo under different conditions and in different neuronal cells. Finally, the role of the p75 receptor in TeT axonal trafficking will be functionally probed using neuronal lines in culture with down-regulation of p75 expression as well as in p75 knock-out mouse models. These experiments will clarify the potential role of p75 in TeT neuronal transport. It could be a major advancement in our understanding of neuronal intoxication and may participate in extending knowledge about poorly understood endogenous retrograde axonal pathways used by neurons for delivery of different trophic molecules during development. Highly efficient TeT trafficking pathway

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through binding to p75 receptor will open an entry gate leading from the periphery to the central nervous system. This may assist in the development of novel modes of delivery of diverse biological agents, including enzymes, analgesics, anesthetic drugs or trophic factors, to the spinal cord and brain stem (Dobrenis et al., 1992; Schneider et al., 2000; Schiavo et al., 2000; Bordet et al., 2001; Kissa et al., 2002). Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •

Project Title: TRANSCUTANEOUS IMMUNIZATION FOR TETANUS BOOSTER Principal Investigator & Institution: Glenn, Gregory M.; Iomai Corporation 20 Firstfield Rd, Ste 250 Gaithersburg, Md 20878 Timing: Fiscal Year 2002; Project Start 01-AUG-1999; Project End 30-JUN-2004 Summary: (Provided by Applicant) Based on extensive animal testing and limited human studies, transcutaneous immunization appears to be a viable and valuable technological improvement to traditional administration of vaccines. The aim of the proposed research plan is to continue commercialization of the technology through further clinical development of the lead tetanus booster product, administered by means of a simple skin patch. The critical activities in this program include: A Phase I human clinical study to further demonstrate safety and immunogenicity at lower adjuvant/antigen ratios. Product development in the area of formulation, analytical methodology, and patch design to yield a stable, commercially viable product design. A subsequent Phase I human study to evaluate the safety and efficacy of the proposed formulation(s) and patch design(s), at the appropriate dose of adjuvant and antigen. Specific outcomes of the work will be a product design that can advance to Phase II/III human studies required for regulatory licensure. Commercial opportunities for a tetanus booster product have been researched and identified, consisting primarily of developing world programs aimed at eliminating maternal and neonatal tetanus, and at-risk populations in developed countries, including those over 50 years of age and other specific at-risk groups. PROPOSED COMMERCIAL APPLICATION: The Transcutaneous tetanus booster is directed to 2 markets: 1. Maternal and neonatal tetanus elimination, primarily in developing countries; and, 2. Adult booster & at-risk population, including the over-50 population and other specific at-risk groups, such as agricultural workers. The commercial introduction of a tetanus vaccine delivered through a patch is expected to increase access to the vaccine and compliance with immunization protocols for the 2 focus markets, thus growing both markets. Additionally, the Transcutaneous booster will decrease the risk of needle-sticks and related disease, and reduce personnel and equipment requirements related to tetanus immunization. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen

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Project Title: TULAREMIA VACCINE DEVELOPMENT Principal Investigator & Institution: Wetzler, Lee M.; Associate Professor; Boston Medical Center Gambro Bldg, 2Nd Fl, 660 Harrison Ave, Ste a Boston, Ma 02118 Timing: Fiscal Year 2003; Project Start 01-JUL-2003; Project End 30-JUN-2008 Summary: Francisella tularensis, a facultative intracellular pathogen, causes significant disease including classic ulceroglandular tularemic infection and the more deadly pulmonary tularemic infection with dissemination and tularemia. Immunity to this potential bioterrorist agent is unclearbut it appears both humoral and cell mediated immunity play a role. The purpose of this project is to investigate the potential protective efficacy of anti-Francisella vaccines consisting of Francisella capsular

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polysaccharide or LPS derived oligosaccharides. As these antigens are classic T-cell independent antigens, the humoral immune response towards these antigens shall be optimized by inducing a T-cell dependent response by 1) either combining these antigens with the vaccine adjuvant, meningococcal porin PorB, or conjugating the antigens to the classic vaccine carrier, tetanus toxoid or 2) convert the epitopes of F-CPS or F-OS to protein based peptide mimotopes. Both these methods are state of the art and have proven to be effective in increasing the efficacy of polysaccharide based vaccines. Most, if not all, effective anti-bacterial vaccines consist of bacterial capsular polysaccharides and this approach has great potential in inducing protection. The aims of this proposal are 1) Preparation of the Francisella capsular polysaccharide (F-CPS) and Francisella LPS derived oligosaccharide (F-OS) vaccine immunogens (combined with various adjuvants), immunization of mice and determination of anti-Francisella IgG levels, 2) Development of F-CPS and F-OS protein mimotpes and optimization of vaccine preparations based on the peptide mimotopes consensus sequences and measurement of IgG antibodies induced by this method that recognize native antigen and intact organism and 3) Determination of the potential protective efficacy of both set of vaccine preparations in Aims 1 and 2 by examining the functional activity of the vaccine induced sera in bactericidal assays, opsonophagocytic assays and prevention of macrophage invasion and measuring the protective effect of vaccination in the murine inhalation model of tularemia. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •

Project Title: VACCINATION WITH TETANUS AND KLH TO ASSESS IMMUNE RESPONSES Principal Investigator & Institution: Miller, Jeffrey S.; Professor; University of Minnesota Twin Cities 200 Oak Street Se Minneapolis, Mn 554552070 Timing: Fiscal Year 2001 Summary: We have been striving toward a goal of using immunotherapy to prevent cancer relapse. One facet of this therapy is to stimulate specific immunity using cancer vaccines. However, tumors are heterogeneous and we hypothesize that the presence of cancer itself, cancer chemotherapy, or more aggressive therapies such as bone marrow transplants may be imuunosuppressive. If this is true, cancer vaccines will not be effective until we can overcome this immunosuppression. We hypothesize that immune stimulating cytokines may be useful for this purpose. If one uses a cancer vaccine strategy and it fails, it is unclear whether failure is due to the cancer vaccine itself or a more generalized lack of responsiveness to any vaccine. To overcome this problem, in this protocol we will test two vaccines which are well characterized and very immunogenic. Tetanus toxoid has been used for decades and almost all individuals have had this. KLH, a foreign protein has been used since the early 1970's to assess immune responses. The major advantage of KLH is that it tests immune response to an antigen that individuals have not had prior exposure to (a so-called antigen). We will use tetanus and KLH to answer a very basic question of whether cancer patients have enough immune competence to respond to proteins which are 100% immunogenic in normal donors. In this protocol, we will stratify patients by their disease type, the amount of standard chemotherapy, and whether or not they will have undergone stem cell transplantation. The role of the GCRC in this protocol would be to administer both vaccines which are given intramuscularly and subcutaneously, to monitor toxicity, and to collect blood samples required for research tests to assess immune response. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen

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Project Title: VERTEBRATE MOTOR AXON GUIDANCE RECEPTORS Principal Investigator & Institution: Wagner Jurata, Linda; Salk Institute for Biological Studies 10010 N Torrey Pines Rd San Diego, Ca 92037 Timing: Fiscal Year 2001; Project Start 01-DEC-2000 Summary: This abstract is not available. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen

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Project Title: VITAMIN A THERAPY IN PRETERM INFANTS: VACCINE RESPONSE Principal Investigator & Institution: Ballow, Mark; Professor of Pediatrics; Pediatrics; State University of New York at Buffalo Suite 211 Ub Commons Amherst, Ny 14228 Timing: Fiscal Year 2001; Project Start 15-SEP-1999; Project End 31-AUG-2003 Summary: The role of vitamin A as an immune modulatory factor has been the focus of many studies both in animals and man. Epidemiologic studies emphasize that vitamin A is essential for supporting the immune system against infection. Despite many therapeutic improvements in recent years, infection still remains a major problem in very low birth weight (VLBW) pre-term infants. Pre-term infants have lower plasma vitamin A (retinol) levels and limited hepatic reserves compared to full term infants. Vitamin A deficiency may lead to increased susceptibility to infection in pre-term infants. Hepatitis B immunization in the neonatal period offers an excellent opportunity to determine what effects vitamin A supplementation has in pre-term infants on their antibody immune response to this vaccine. VLBW pre-term infants less than 1500g (less than 32 weeks gestation) will be randomized into two treatment groups: vitamin A supplemented and placebo (saline). The vitamin A treatment group will receive 2000 IU of retinyl palmitate by intramuscular injection starting on postnatal day 2 and thereafter on alternate days for 28 days. Plasma vitamin A levels will be closely monitored for toxicity. Plasma immunoglobulins and antibodies to HbsAg and tetanus toxoid will be quantified by ELISA after the second and third doses of hepatitis B vaccine. These results will be correlated with changes in CD4+ T-cell subsets as defined by their cytokine secretion profile and the proportion of naive (CD45RA) to memory (CD45R0) T-cells as analyzed by flow cytometry. Acceleration in the maturation of T-cells (naive to memory), and augmentation in the proportion of intracellular cytokine producing Tcells will provide a mechanism for the enhancement in the humoral immune responses to hepatitis B vaccine by vitamin A supplementation. Finally, the type and number of infections in the NICU and to 9 months of age will be recorded to determine if vitamin A supplementation affects the incidence and severity of infection in early infancy. Vitamin A supplementation may be useful in pre-term infants in augmenting B-cell immune responses to infectious agents and in their response to vaccines. These factors could lead to decreased morbidity and mortality of pre-term infants during early postnatal life. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen

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 3 Adapted

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

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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 “tetanus” (or synonyms) into the search box. This search gives you access to fulltext articles. The following is a sample of items found for tetanus in the PubMed Central database: •

A Novel Tetanus Neurotoxin-insensitive Vesicle-associated Membrane Protein in SNARE Complexes of the Apical Plasma Membrane of Epithelial Cells. by Galli T, Zahraoui A, Vaidyanathan VV, Raposo G, Tian JM, Karin M, Niemann H, Louvard D.; 1998 Jun 1; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=25366

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A Recombinant Live Attenuated Strain of Vibrio cholerae Induces Immunity against Tetanus Toxin and Bordetella pertussis Tracheal Colonization Factor. by Chen I, Finn TM, Yanqing L, Guoming Q, Rappuoli R, Pizza M.; 1998 Apr; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=108100

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Aging and the Immune Response to Tetanus Toxoid: Diminished Frequency and Level of Cellular Immune Reactivity to Antigenic Stimulation. by Schatz D, Ellis T, Ottendorfer E, Jodoin E, Barrett D, Atkinson M.; 1998 Nov; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=96220

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Antigen-Specific Responses to Diphtheria-Tetanus-Acellular Pertussis Vaccine in Human Infants Are Initially Th2 Polarized. by Rowe J, Macaubas C, Monger TM, Holt BJ, Harvey J, Poolman JT, Sly PD, Holt PG.; 2000 Jul; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=101661

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Cell Surface-Exposed Tetanus Toxin Fragment C Produced by Recombinant Bacillus anthracis Protects against Tetanus Toxin. by Mesnage S, Weber-Levy M, Haustant M, Mock M, Fouet A.; 1999 Sep; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=96818

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Characterization of recombinant tetanus toxin derivatives suitable for vaccine development. by Figueiredo D, Turcotte C, Frankel G, Li Y, Dolly O, Wilkin G, Marriott D, Fairweather N, Dougan G.; 1995 Aug; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&rendertype=abstr act&artid=173441

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Cloning, nucleotide sequencing, and expression of tetanus toxin fragment C in Escherichia coli. by Fairweather NF, Lyness VA, Pickard DJ, Allen G, Thomson RO.; 1986 Jan; http://www.pubmedcentral.gov/picrender.fcgi?tool=pmcentrez&action=stream&blobt ype=pdf&artid=214364

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Comparative immunogenicity of conjugates composed of Escherichia coli O111 Ospecific polysaccharide, prepared by treatment with acetic acid or hydrazine, bound to tetanus toxoid by two synthetic schemes. by Gupta RK, Egan W, Bryla DA, Robbins JB, Szu SC.; 1995 Aug; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&rendertype=abstr act&artid=173380

4 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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Comparison of a Multiplex Flow Cytometric Assay with Enzyme-Linked Immunosorbent Assay for Quantitation of Antibodies to Tetanus, Diphtheria, and Haemophilus influenzae Type b. by Pickering JW, Martins TB, Schroder MC, Hill HR.; 2002 Jul; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=120020

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Construction, Expression, and Immunogenicity of the Schistosoma mansoni P28 Glutathione S-Transferase as a Genetic Fusion to Tetanus Toxin Fragment C in a Live Aro Attenuated Vaccine Strain of Salmonella. by Khan CM, Villarreal-Ramos B, Pierce RJ, Riveau G, Hormaeche RD, McNeill H, Ali T, Fairweather N, Chatfield S, Capron A, Dougan G, Hormaeche CE.; 1994 Nov 8; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&rendertype=abstr act&artid=45207

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Evaluation of De-O-Acetylated Meningococcal C Polysaccharide-Tetanus Toxoid Conjugate Vaccine in Infancy: Reactogenicity, Immunogenicity, Immunologic Priming, and Bactericidal Activity against O-Acetylated and De-O-Acetylated Serogroup C Strains. by Richmond P, Borrow R, Findlow J, Martin S, Thornton C, Cartwright K, Miller E.; 2001 Apr; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=98168

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Evaluation of the Safety and Pharmacokinetic Profile of a New, Pasteurized, Human Tetanus Immunoglobulin Administered as Sham, Postexposure Prophylaxis of Tetanus. by Forrat R, Dumas R, Seiberling M, Merz M, Lutsch C, Lang J.; 1998 Feb; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=105404

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Exogenous mRNA Encoding Tetanus or Botulinum Neurotoxins Expressed in Aplysia Neurons. by Mochida S, Poulain B, Eisel U, Binz T, Kurazono H, Niemann H, Tauc L.; 1990 Oct 15; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&rendertype=abstr act&artid=54846

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Expression and immunogenicity of pertussis toxin S1 subunit-tetanus toxin fragment C fusions in Salmonella typhi vaccine strain CVD 908. by Barry EM, Gomez-Duarte O, Chatfield S, Rappuoli R, Pizza M, Losonsky G, Galen J, Levine MM.; 1996 Oct; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&rendertype=abstr act&artid=174353

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Expression of tetanus toxin Fragment C in tobacco chloroplasts. by Tregoning JS, Nixon P, Kuroda H, Svab Z, Clare S, Bowe F, Fairweather N, Ytterberg J, Wijk KJ, Dougan G, Maliga P.; 2003 Feb 15; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=150239

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Functional Antibody Activity Elicited by Fractional Doses of Haemophilus influenzae Type b Conjugate Vaccine (Polyribosylribitol Phosphate --Tetanus Toxoid Conjugate). by Romero-Steiner S, Fernandez J, Biltoft C, Wohl ME, Sanchez J, Feris J, Balter S, Levine OS, Carlone GM.; 2001 Nov; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=96235

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Human Onchocerciasis and Tetanus Vaccination: Impact on the Postvaccination Antitetanus Antibody Response. by Cooper PJ, Espinel I, Wieseman M, Paredes W, Espinel M, Guderian RH, Nutman TB.; 1999 Nov; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=96979

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Humoral and Cellular Immune Responses in Mice Immunized with Recombinant Mycobacterium bovis Bacillus Calmette-Guerin Producing a Pertussis Toxin-Tetanus

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Toxin Hybrid Protein. by Abomoelak B, Huygen K, Kremer L, Turneer M, Locht C.; 1999 Oct; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=96858 •

Identification of Human Antibody Fragment Clones Specific for Tetanus Toxoid in a Bacteriophage [lambda] Immunoexpression Library. by Mullinax RL, Gross EA, Amberg JR, Hay BN, Hogrefe HH, Kubitz MM, Greener A, Alting-Mees M, Ardourel D, Short JM, Sorge JA, Shopes B.; 1990 Oct 15; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&rendertype=abstr act&artid=54899

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Immune response in mice following immunization with DNA encoding fragment C of tetanus toxin. by Anderson R, Gao XM, Papakonstantinopoulou A, Roberts M, Dougan G.; 1996 Aug; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&rendertype=abstr act&artid=174203

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Immunogenicity and protection in small-animal models with controlled-release tetanus toxoid microparticles as a single-dose vaccine. by Singh M, Li XM, Wang H, McGee JP, Zamb T, Koff W, Wang CY, O'Hagan DT.; 1997 May; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&rendertype=abstr act&artid=175204

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Immunogenicity of group B Streptococcus type III polysaccharide-tetanus toxoid vaccine in baboons. by Paoletti LC, Kennedy RC, Chanh TC, Kasper DL.; 1996 Feb; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&rendertype=abstr act&artid=173821

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Immunoglobulin G (IgG) Subclass Distribution and IgG1 Avidity of Antibodies in Human Immunodeficiency Virus-Infected Individuals after Revaccination with Tetanus Toxoid. by Kroon FP, van Tol MJ, Jol-van der Zijde CM, van Furth R, van Dissel JT.; 1999 May; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=103722

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Impaired human responses to tetanus toxoid in vitamin A-deficient SCID mice reconstituted with human peripheral blood lymphocytes. by Molrine DC, Polk DB, Ciamarra A, Phillips N, Ambrosino DM.; 1995 Aug; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&rendertype=abstr act&artid=173389

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Influence of preimmunization with tetanus toxoid on immune responses to tetanus toxin fragment C-guest antigen fusions in a Salmonella vaccine carrier. by Chabalgoity JA, Villareal-Ramos B, Khan CM, Chatfield SN, de Hormaeche RD, Hormaeche CE.; 1995 Jul; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&rendertype=abstr act&artid=173343

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Isotypes and Opsonophagocytosis of Pneumococcus Type 6B Antibodies Elicited in Infants and Adults by an Experimental Pneumococcus Type 6B-Tetanus Toxoid Vaccine. by Vidarsson G, Sigurdardottir ST, Gudnason T, Kjartansson S, Kristinsson KG, Ingolfsdottir G, Jonsson S, Valdimarsson H, Schiffman G, Schneerson R, Jonsdottir I.; 1998 Jun; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=108283

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Levels of Antibodies Specific to Tetanus Toxoid, Haemophilus influenzae Type b, and Pneumococcal Capsular Polysaccharide in Healthy Children and Adults. by

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Schauer U, Stemberg F, Rieger CH, Buttner W, Borte M, Schubert S, Mollers H, Riedel F, Herz U, Renz H, Herzog W.; 2003 Mar; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=150524 •

Lipid Rafts Act as Specialized Domains for Tetanus Toxin Binding and Internalization into Neurons. by Herreros J, Ng T, Schiavo G.; 2001 Oct 1; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=60147

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Long-Term Pertussis-Specific Immunity after Primary Vaccination with a Combined Diphtheria, Tetanus, Tricomponent Acellular Pertussis, and Hepatitis B Vaccine in Comparison with That after Natural Infection. by Esposito S, Agliardi T, Giammanco A, Faldella G, Cascio A, Bosis S, Friscia O, Clerici M, Principi N.; 2001 Jul; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=98527

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Mucosal Immune Responses and Protection against Tetanus Toxin after Intranasal Immunization with Recombinant Lactobacillus plantarum. by Grangette C, MullerAlouf H, Goudercourt D, Geoffroy MC, Turneer M, Mercenier A.; 2001 Mar; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=98054

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Neuronal Lysosomal Enzyme Replacement Using Fragment C of Tetanus Toxin. by Dobrens K, Joseph A, Rattazzi MC.; 1992 Mar 15; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&rendertype=abstr act&artid=48644

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Oral Vaccination against Tetanus: Comparison of the Immunogenicities of Salmonella Strains Expressing Fragment C from the nirB and htrA Promoters. by Roberts M, Li J, Bacon A, Chatfield S.; 1998 Jul; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=108316

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Phase 1 and Phase 2 Studies of Salmonella enterica Serovar Paratyphi A O-Specific Polysaccharide-Tetanus Toxoid Conjugates in Adults, Teenagers, and 2- to 4-Year-Old Children in Vietnam. by Konadu EY, Lin FY, Ho VA, Thuy NT, Van Bay P, Thanh TC, Khiem HB, Trach DD, Karpas AB, Li J, Bryla DA, Robbins JB, Szu SC.; 2000 Mar; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=97311

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Postoperative tetanus: a case report. by Katz KC, Walmsley SL.; 2000 Sep 5; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=80467

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Preclinical immunoprophylactic and immunotherapeutic efficacy of antisera to capsular polysaccharide-tetanus toxoid conjugate vaccines of Vibrio vulnificus. by Devi SJ, Hayat U, Powell JL, Morris JG Jr.; 1996 Jun; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&rendertype=abstr act&artid=174059

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Preparation, Immunogenicity, and Protective Efficacy, in a Murine Model, of a Conjugate Vaccine Composed of the Polysaccharide Moiety of the Lipopolysaccharide of Vibrio cholerae O139 Bound to Tetanus Toxoid. by Boutonnier A, Villeneuve S, Nato F, Dassy B, Fournier JM.; 2001 May; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=98317

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Prior Immunity to Homologous and Heterologous Salmonella Serotypes Suppresses Local and Systemic Anti-Fragment C Antibody Responses and Protection from Tetanus Toxin in Mice Immunized with Salmonella Strains Expressing Fragment C. by Roberts M, Bacon A, Li J, Chatfield S.; 1999 Aug; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=96658

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Protection against Tetanus by Needle-Free Inoculation of Adenovirus-Vectored Nasal and Epicutaneous Vaccines. by Shi Z, Zeng M, Yang G, Siegel F, Cain LJ, van Kampen KR, Elmets CA, Tang DC.; 2001 Dec 1; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=114734

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Rapid, simplified method for production and purification of tetanus toxin. by Ozutsumi K, Sugimoto N, Matsuda M.; 1985 Apr; http://www.pubmedcentral.gov/picrender.fcgi?tool=pmcentrez&action=stream&blobt ype=pdf&artid=238473

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Rates of tetanus protection and transplacental tetanus antibody transfer in pregnant women from different socioeconomic groups in Peru. by Madico G, Salazar G, McDonald J, Checkley W, Calderon M, Verastegui M, Gilman RH.; 1996 Nov; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&rendertype=abstr act&artid=170442

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Safety and immunogenicity of three doses of an eleven-valent diphtheria toxoid and tetanus protein -- conjugated pneumococcal vaccine in Filipino infants. by Capeding MZ, Puumalainen T, Gepanayao CP, Kayhty H, Lucero MG, Nohynek H.; 2003; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=184484

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Stabilization of Tetanus and Diphtheria Toxoids Against Moisture-Induced Aggregation. by Schwendeman SP, Costantino HR, Gupta RK, Siber GR, Klibanov AM, Langer R.; 1995 Nov 21; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&rendertype=abstr act&artid=40606

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Synaptic vesicle endocytosis mediates the entry of tetanus neurotoxin into hippocampal neurons. by Matteoli M, Verderio C, Rossetto O, Iezzi N, Coco S, Schiavo G, Montecucco C.; 1996 Nov 12; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=24089

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Synaptobrevin/Vesicle-Associated Membrane Protein (VAMP) of Aplysi californica: Structure and Proteolysis by Tetanus Toxin and Botulinal Neurotoxins Type D and F. by Yamasaki S, Hu Y, Binz T, Kalkuhl A, Kurazono H, Tamura T, Jahn R, Kandel E, Neimann H.; 1994 May 24; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&rendertype=abstr act&artid=43853

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Synthesis, characterization, and immunological properties in mice of conjugates composed of detoxified lipopolysaccharide of Salmonella paratyphi A bound to tetanus toxoid with emphasis on the role of O acetyls. by Konadu E, Shiloach J, Bryla DA, Robbins JB, Szu SC.; 1996 Jul; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&rendertype=abstr act&artid=174130

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Tetanus Toxin Fragment C Expressed in Live Salmonella Vaccines Enhances Antibody Responses to Its Fusion Partner Schistosoma haematobium Glutathione STransferase. by Lee JJ, Sinha KA, Harrison JA, de Hormaeche RD, Riveau G, Pierce RJ, Capron A, Wilson RA, Khan CM.; 2000 May; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=97452

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TetR Is a Positive Regulator of the Tetanus Toxin Gene in Clostridium tetani and Is Homologous to BotR. by Marvaud JC, Eisel U, Binz T, Niemann H, Popoff MR.; 1998 Dec; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=108720

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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 tetanus, simply go to the PubMed Web site at http://www.ncbi.nlm.nih.gov/pubmed. Type “tetanus” (or synonyms) into the search box, and click “Go.” The following is the type of output you can expect from PubMed for tetanus (hyperlinks lead to article summaries): •

A 5-year follow-up on antibody response after diphtheria and tetanus vaccination in hemodialysis patients. Author(s): Kruger S, Muller-Steinhardt M, Kirchner H, Kreft B. Source: American Journal of Kidney Diseases : the Official Journal of the National Kidney Foundation. 2001 December; 38(6): 1264-70. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11728959&dopt=Abstract

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A case of Bickerstaff's brainstem encephalitis mimicking tetanus. Author(s): Saito T, Miyai I, Matsumura T, Nozaki S, Kang J, Fujita H, Sugimoto N, Yuki N. Source: Journal of Neurology, Neurosurgery, and Psychiatry. 2000 November; 69(5): 695-6. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11032635&dopt=Abstract

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A case of maternal tetanus in Korea. Author(s): Shin DH, Park JH, Jung PJ, Lee SR, Shin JH, Kim SJ. Source: Journal of Korean Medical Science. 2002 April; 17(2): 260-2. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11961314&dopt=Abstract

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A case of myositis ossificans as a complication of tetanus treated by surgical excision. Author(s): Karapinar H, Yagdi S. Source: Acta Orthop Belg. 2003 June; 69(3): 285-8. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12879713&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.

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A combined liquid Hib (PRP-OMPC), hepatitis B, diphtheria, tetanus and whole-cell pertussis vaccine: controlled studies of immunogenicity and reactogenicity. Author(s): Nolan T, Hogg G, Darcy MA, Skeljo M, Carlin J, Boslego J. Source: Vaccine. 2001 February 28; 19(15-16): 2127-37. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11228385&dopt=Abstract

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A diphtheria-tetanus-acellular pertussis vaccine for adults: the wrong booster vaccine for Australia? Author(s): Kelly HA, Andrews RM. Source: The Medical Journal of Australia. 2001 August 6; 175(3): 173-4. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11548090&dopt=Abstract

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A method for adjusting gender bias in neonatal tetanus reports in Egypt 1991. Author(s): Silvers MJ, Haddy R. Source: Epidemiology and Infection. 2002 April; 128(2): 169-74. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12002534&dopt=Abstract

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A randomized double-blind sham-controlled study of intrathecal human anti-tetanus immunoglobulin in the management of tetanus. Author(s): Agarwal M, Thomas K, Peter JV, Jeyaseelan L, Cherian AM. Source: Natl Med J India. 1998 September-October; 11(5): 209-12. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10997166&dopt=Abstract

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A randomized trial of two acellular pertussis vaccines (dTpa and pa) and a licensed diphtheria-tetanus vaccine (Td) in adults. Author(s): Turnbull FM, Heath TC, Jalaludin BB, Burgess MA, Ramalho AC. Source: Vaccine. 2000 November 8; 19(6): 628-36. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11090714&dopt=Abstract

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A single case of orthotopic liver transplantation with a graft from a donor with tetanus. Author(s): Zamboni F, Livigni S, Ricci P, Salizzoni M. Source: Transplant International : Official Journal of the European Society for Organ Transplantation. 2000; 13(3): 234-5. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10935709&dopt=Abstract

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A ten-year retrospective study of tetanus at a general hospital in Malaysia. Author(s): Lau LG, Kong KO, Chew PH. Source: Singapore Med J. 2001 August; 42(8): 346-50. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11764050&dopt=Abstract

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About intrathecal baclofen in tetanus. Author(s): Engrand N, Benhamou D. Source: Anaesthesia and Intensive Care. 2001 June; 29(3): 306-7. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11439811&dopt=Abstract

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Absence of a significant interaction between a Haemophilus influenzae conjugate vaccine combined with a diphtheria toxoid, tetanus toxoid and acellular pertussis vaccine in the same syringe and inactivated polio vaccine. Author(s): Daum RS, Zenko CE, Given GZ, Ballanco GA, Parikh H, Vidor E, Liu X. Source: The Pediatric Infectious Disease Journal. 2000 August; 19(8): 710-7. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10959738&dopt=Abstract

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Acceptability of tetanus toxoid vaccine by pregnant women in two health centres in Abidjan (Ivory Coast). Author(s): Ymba A, Perrey C. Source: Vaccine. 2003 July 28; 21(24): 3497-500. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12850368&dopt=Abstract

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Accidental tetanus: prognosis evaluation in a historical series at a hospital in Salvador, Bahia, Brazil. Author(s): Greco JB, Tavares-Neto J, Greco Junior JB. Source: Revista Do Instituto De Medicina Tropical De Sao Paulo. 2003 January-February; 45(1): 35-40. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12751320&dopt=Abstract

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Acid secretion of parietal cells is paralleled by a redistribution of NSF and alpha, beta-SNAPs and inhibited by tetanus toxin. Author(s): Lehnardt S, Ahnert-Hilger G, Bigalke H, Jons T. Source: Histochemistry and Cell Biology. 2000 November; 114(5): 387-91. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11151408&dopt=Abstract

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Acute myocarditis associated with tetanus vaccination. Author(s): Dilber E, Karagoz T, Aytemir K, Ozer S, Alehan D, Oto A, Celiker A. Source: Mayo Clinic Proceedings. 2003 November; 78(11): 1431-3. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=14601707&dopt=Abstract

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Acute myopericarditis after diphtheria, tetanus, and polio vaccination. Author(s): Boccara F, Benhaiem-Sigaux N, Cohen A. Source: Chest. 2001 August; 120(2): 671-2. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11502677&dopt=Abstract

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Adequate immune response to tetanus toxoid and failure of vitamin A and E supplementation to enhance antibody response in healthy children. Author(s): Kutukculer N, Akil T, Egemen A, Kurugol Z, Aksit S, Ozmen D, Turgan N, Bayindir O, Caglayan S. Source: Vaccine. 2000 July 1; 18(26): 2979-84. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10825599&dopt=Abstract

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Adult tetanus immunisation. Author(s): Dutta TK. Source: J Indian Med Assoc. 2000 January; 98(1): 31. No Abstract Available. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11016146&dopt=Abstract

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Age-specific seroprevalence of poliomyelitis, diphtheria and tetanus antibodies in Spain. Author(s): Pachon I, Amela C, De Ory F. Source: Epidemiology and Infection. 2002 December; 129(3): 535-41. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12558336&dopt=Abstract

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Allergy to tetanus toxoid vaccine. Author(s): Bellioni Businco B, Paganelli R, Bruno G, Grossi O, Di Rienzo A, Businco L. Source: Allergy. 2001 July; 56(7): 701-2. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11421933&dopt=Abstract

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An audit of the tetanus immunisation status of plastic surgery trauma and burns patients. Author(s): Cassell OC, Fitton AJ, Dickson WA, Milling MA. Source: British Journal of Plastic Surgery. 2002 April; 55(3): 215-8. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12041974&dopt=Abstract

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Analysis of the case fatality rate of tetanus among adults in a tertiary hospital in Turkey. Author(s): Ergonul O, Erbay A, Eren S, Dokuzoguz B. Source: European Journal of Clinical Microbiology & Infectious Diseases : Official Publication of the European Society of Clinical Microbiology. 2003 March; 22(3): 188-90. Epub 2003 March 01. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12649718&dopt=Abstract

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Analysis of the immune response against tetanus toxoid: enumeration of specific T helper cells by the Elispot assay. Author(s): Mayer S, Laumer M, Mackensen A, Andreesen R, Krause SW. Source: Immunobiology. 2002 July; 205(3): 282-9. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12182454&dopt=Abstract

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Anaphylactic reaction to diphtheria-tetanus vaccine in a child: specific IgE/IgG determinations and cross-reactivity studies. Author(s): Martin-Munoz MF, Pereira MJ, Posadas S, Sanchez-Sabate E, Blanca M, Alvarez J. Source: Vaccine. 2002 September 10; 20(27-28): 3409-12. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12213411&dopt=Abstract

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Anaphylaxis to antitetanus toxoid serum. Author(s): Demoly P, Botros HG, Rabillon J, David B, Bousquet J. Source: Allergy. 2002 September; 57(9): 860-1. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12169188&dopt=Abstract

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Antibodies to tetanus toxoid in women of childbearing age in Dar es Salaam and Bagamoyo, Tanzania. Author(s): Aboud S, Matre R, Lyamuya EF, Kristoffersen EK. Source: Tropical Medicine & International Health : Tm & Ih. 2001 February; 6(2): 119-25. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11251908&dopt=Abstract

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Antibody modulation of antigen presentation: positive and negative effects on presentation of the tetanus toxin antigen via the murine B cell isoform of FcgammaRII. Author(s): Antoniou AN, Watts C. Source: European Journal of Immunology. 2002 February; 32(2): 530-40. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11828370&dopt=Abstract

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Antibody response to a single tetanus toxoid booster in young women in rural south India. Author(s): Aruldas K, Muliyil JP, Mathai E, Abraham S, Joseph A, Inbamalar U, Aruldas V. Source: Natl Med J India. 2001 January-February; 14(1): 22-3. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11242693&dopt=Abstract

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Antibody response to an eleven valent diphtheria- and tetanus-conjugated pneumococcal conjugate vaccine in Filipino infants. Author(s): Puumalainen T, Zeta-Capeding MR, Kayhty H, Lucero MG, Auranen K, Leroy O, Nohynek H. Source: The Pediatric Infectious Disease Journal. 2002 April; 21(4): 309-14. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12075762&dopt=Abstract

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Antibody response to Haemophilus influenzae type b tetanus conjugate vaccine with two doses given at 3 and 5 months of age. Author(s): Guimaraes T, Cereda RF, Bianchin PJ, Nagao AT, Sampaio MC, Mendonca JS. Source: International Journal of Infectious Diseases : Ijid : Official Publication of the International Society for Infectious Diseases. 2002 June; 6(2): 113-7. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12121598&dopt=Abstract

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Antibody responses of healthy infants to concurrent administration of a bivalent haemophilus influenzae type b-hepatitis B vaccine with diphtheria-tetanus-pertussis, polio and measles-mumps-rubella vaccines. Author(s): West DJ, Rabalais GP, Watson B, Keyserling HL, Matthews H, Hesley TM. Source: Biodrugs : Clinical Immunotherapeutics, Biopharmaceuticals and Gene Therapy. 2001; 15(6): 413-8. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11520252&dopt=Abstract

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Antihepatitis B response to hepatitis B vaccine administered simultaneously with tetanus toxoid in nonresponder individuals. Author(s): Sonmez E, Sonmez AS, Bayindir Y, Coskun D, Ariturk S. Source: Vaccine. 2002 December 13; 21(3-4): 243-6. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12450699&dopt=Abstract

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Antitetanus and antidiphtheria immunity in newborns. Author(s): Durbaca S. Source: Roum Arch Microbiol Immunol. 1999 July-December; 58(3-4): 267-72. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11845464&dopt=Abstract

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Anti-tetanus toxoid antibody production and protection against lethal doses of tetanus toxin in hu-PBL-SCID mice. Author(s): Naito S, Okada Y, Takahashi M, Kato H, Taneichi M, Ami Y, Suzaki Y, Oka T, Okuma K, Morokuma K, Onodera H, Inoue M, Takahashi Y, Yamazaki S, Kimura H, Komuro K, Uchida T. Source: International Archives of Allergy and Immunology. 2000 October; 123(2): 149-54. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11060487&dopt=Abstract

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Arthritis following combined vaccine against diphtheria, polyomyelitis, and tetanus toxoid. Author(s): Maillefert JF, Tonolli-Serabian I, Cherasse A, Demoux AL, Tavernier C, Piroth L. Source: Clin Exp Rheumatol. 2000 March-April; 18(2): 255-6. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10812502&dopt=Abstract

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Assessment of neonatal tetanus elimination in an African setting by lot quality assurance cluster sampling (LQA-CS). Author(s): Cotter B, Bremer V, Stroh G, Msambichaka K, Mabuzane E, Munyoro M, Shirehwa F, Biellik R, Birmingham M. Source: Epidemiology and Infection. 2003 April; 130(2): 221-6. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12729190&dopt=Abstract

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Associated or combined vaccination of Brazilian infants with a conjugate Haemophilus influenzae type b (Hib) vaccine, a diphtheria-tetanus-whole-cell pertussis vaccine and IPV or OPV elicits protective levels of antibodies against Hib. Author(s): Araujo OO, Forleo-Neto E, Vespa GN, Puccini RF, Weckx LW, Carvalho ES, Farhat CK. Source: Vaccine. 2000 September 15; 19(2-3): 367-75. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10930692&dopt=Abstract

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Autonomic nervous system dysfunction in children with severe tetanus: dissociation of cardiac and vascular sympathetic control. Author(s): Mazzei de Davila CA, Davila DF, Donis JH, Gonzalo X. Source: Brazilian Journal of Medical and Biological Research = Revista Brasileira De Pesquisas Medicas E Biologicas / Sociedade Brasileira De Biofisica. [et Al.]. 2003 June; 36(6): 815-9. Epub 2003 June 03. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12792712&dopt=Abstract

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BCG vaccination among West African infants is associated with less anergy to tuberculin and diphtheria-tetanus antigens. Author(s): Garly ML, Bale C, Martins CL, Balde MA, Hedegaard KL, Whittle HC, Aaby P. Source: Vaccine. 2001 November 12; 20(3-4): 468-74. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11672911&dopt=Abstract

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Bilateral compartment syndrome of the leg complicating tetanus infection. Author(s): Loren GJ, Mohler LR, Pedowitz RA. Source: Orthopedics. 2001 October; 24(10): 997-9. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11688783&dopt=Abstract

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Blink reflexes and the silent period in tetanus. Author(s): Poncelet AN. Source: Muscle & Nerve. 2000 September; 23(9): 1435-8. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10951449&dopt=Abstract

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Booster effect of low doses of tetanus toxoid in elderly vaccinees. Author(s): Bjorkholm B, Hagberg L, Sundbeck G, Granstrom M. Source: European Journal of Clinical Microbiology & Infectious Diseases : Official Publication of the European Society of Clinical Microbiology. 2000 March; 19(3): 195-9. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10795592&dopt=Abstract

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Booster response to the tetanus and diphtheria toxoid carriers of 11-valent pneumococcal conjugate vaccine in adults and toddlers. Author(s): Olander RM, Wuorimaa T, Kayhty H, Leroy O, Dagan R, Eskola J. Source: Vaccine. 2001 November 12; 20(3-4): 336-41. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11672895&dopt=Abstract

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Botulinum and tetanus neurotoxins: structure, function and therapeutic utility. Author(s): Turton K, Chaddock JA, Acharya KR. Source: Trends in Biochemical Sciences. 2002 November; 27(11): 552-8. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12417130&dopt=Abstract

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Brain damage after neonatal tetanus in a rural Kenyan hospital. Author(s): Barlow JL, Mung'Ala-Odera V, Gona J, Newton CR. Source: Tropical Medicine & International Health : Tm & Ih. 2001 April; 6(4): 305-8. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11348521&dopt=Abstract

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Brain lesions in the course of generalised tetanus. Author(s): Ijichi T, Yamada T, Yoneda S, Kajita Y, Nakajima K, Nakagawa M. Source: Journal of Neurology, Neurosurgery, and Psychiatry. 2003 October; 74(10): 14324. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=14570841&dopt=Abstract

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Bronchoaspiration as a possible cause in a case of tetanus. A reminder on the importance of adulthood immunizations. Author(s): Ostrosky-Zeichner L, Volkow P, Ponce de Leon S. Source: Revista De Investigacion Clinica; Organo Del Hospital De Enfermedades De La Nutricion. 1999 March-April; 51(2): 117-9. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10410591&dopt=Abstract

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Calibration of replacement international standard and European pharmacopoeia biological reference preparation for tetanus toxoid, adsorbed. Author(s): Sesardic D, Winsnes R, Rigsby P, Tierney R, Gaines-Das R. Source: Biologicals : Journal of the International Association of Biological Standardization. 2002 March; 30(1): 49-68. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11846430&dopt=Abstract

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Can epidural anesthesia change the mortality rate of tetanus? Author(s): Nishanian E. Source: Critical Care Medicine. 1999 September; 27(9): 2025-6. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10507637&dopt=Abstract

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CDC advises delaying tetanus booster shots for adults, adolescents until 2002. Author(s): Thompson CA. Source: American Journal of Health-System Pharmacy : Ajhp : Official Journal of the American Society of Health-System Pharmacists. 2001 July 1; 58(13): 1170. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11449869&dopt=Abstract

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Cephalic tetanus as a result of rooster pecking: an unusual case. Author(s): Kara CO, Cetin CB, Yalcin N. Source: Scandinavian Journal of Infectious Diseases. 2002; 34(1): 64-6. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11874169&dopt=Abstract

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Cephalic tetanus following minor facial abrasions: report of a case. Author(s): De Paz A, Izquierdo M, Redondo LM, Verrier A. Source: Journal of Oral and Maxillofacial Surgery : Official Journal of the American Association of Oral and Maxillofacial Surgeons. 2001 July; 59(7): 800-1. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11429744&dopt=Abstract

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Changes in severe accidental tetanus mortality in the ICU during two decades in Brazil. Author(s): Brauner JS, Vieira SR, Bleck TP. Source: Intensive Care Medicine. 2002 July; 28(7): 930-5. Epub 2002 May 28. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12122532&dopt=Abstract

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Childhood tetanus in Australia: ethical issues for a should-be-forgotten preventable disease. Author(s): Goldwater PN, Braunack-Mayer AJ, Power RG, Henning PH, Gold MS, Donald TG, Jureidini JN, Finlay CF. Source: The Medical Journal of Australia. 2003 February 17; 178(4): 175-7. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12580746&dopt=Abstract

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Circumcision and neonatal tetanus: disclosure of risk and its reduction by topical antibiotics. Author(s): Bennett J, Breen C, Traverso H, Agha SB, Macia J, Boring J. Source: International Journal of Epidemiology. 1999 April; 28(2): 263-6. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10342689&dopt=Abstract

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Clinical and management factors related to outcome in neonatal tetanus. Author(s): Okoromah CN, Lesi FE, Egri-Okwaji MT, Iroha E. Source: Niger Postgrad Med J. 2003 June; 10(2): 92-5. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=14567043&dopt=Abstract

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Collaborative study for the establishment of a European Pharmacopoeia Biological Reference Preparation for serological potency testing of tetanus vaccines for human use: Clostridium tetani guinea pig antiserum (human). Author(s): Hendriksen C, van der Gun J, Winsnes R, Urdal T, Rautmann G, EspositoFarese ME. Source: Pharmeuropa Spec Issue Biol. 2001 August; 2001(1): 7-11. No Abstract Available. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11705101&dopt=Abstract

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Combined vaccination of Haemophilus influenzae type b conjugate and diphtheriatetanus-pertussis containing acellular pertussis. Author(s): Eskola J, Ward J, Dagan R, Goldblatt D, Zepp F, Siegrist CA. Source: Lancet. 1999 December 11; 354(9195): 2063-8. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10636384&dopt=Abstract

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Comparative trial to assess the reactogenicity of the diphtheria-tetanus-acellular pertussis (DTPa) vaccine plus Haemophilus influenzae type B (Hib) conjugate vaccine and that of the diphtheria-tetanus-whole cell pertussis (DTPw) vaccine plus Hib conjugate vaccine, administered in single injection a. Author(s): Calbo F, Dal-Re R, Diez-Delgado J, Ona S, Sanchez-Prados F, Garcia-Corbeira P; DTPa/Hi 067 Study Group. Source: Medicina Clinica. 2002 January 19; 118(1): 1-4. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11803003&dopt=Abstract

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Comparison of a multiplex flow cytometric assay with enzyme-linked immunosorbent assay for auantitation of antibodies to tetanus, diphtheria, and Haemophilus influenzae Type b. Author(s): Pickering JW, Martins TB, Schroder MC, Hill HR. Source: Clinical and Diagnostic Laboratory Immunology. 2002 July; 9(4): 872-6. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12093688&dopt=Abstract

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Comparison of the immune responses induced by local immunizations with recombinant Lactobacillus plantarum producing tetanus toxin fragment C in different cellular locations. Author(s): Reveneau N, Geoffroy MC, Locht C, Chagnaud P, Mercenier A. Source: Vaccine. 2002 March 15; 20(13-14): 1769-77. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11906764&dopt=Abstract

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Complex cytokine responses to hepatitis B surface antigen and tetanus toxoid in responders, nonresponders and subjects naive to hepatitis B surface antigen. Author(s): Larsen CE, Xu J, Lee S, Dubey DP, Uko G, Yunis EJ, Alper CA. Source: Vaccine. 2000 July 1; 18(26): 3021-30. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10825606&dopt=Abstract

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Concurrent administration of rhesus rotavirus tetravalent (RRV-TV) vaccine with pentavalent diphtheria-pertussis-tetanus-Haemophilus influenzae beta-inactivated polio and hepatitis B vaccines. Author(s): Vesikari T, Joensuu J, Baer M, Kayhty H, Olander RM, Sormunen H, Miettinen A, Ward RL, Guillot T. Source: Acta Paediatrica (Oslo, Norway : 1992). 1999 May; 88(5): 513-20. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10426173&dopt=Abstract

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Consistency testing of diphtheria and tetanus to replace potency testing for lot release. Author(s): Kreeftenberg JG. Source: Dev Biol (Basel). 2002; 111: 291-8. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12678252&dopt=Abstract

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Craniocervical tetanus presenting with dysphagia: diagnostic value of electrophysiological studies. Author(s): Mastaglia FL, Thickbroom GW, Day T, Bond R. Source: Journal of Neurology. 2001 October; 248(10): 903-4. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11697530&dopt=Abstract

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Cross reaction of tetanus and botulinum neurotoxins A and B and the boosting effect of botulinum neurotoxins A and B on a primary anti-tetanus antibody response. Author(s): Dolimbek BZ, Jankovic J, Atassi MZ. Source: Immunological Investigations. 2002 August-November; 31(3-4): 247-62. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12472183&dopt=Abstract

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Death from tetanus after a pretibial laceration. Author(s): Cassell OC. Source: Bmj (Clinical Research Ed.). 2002 June 15; 324(7351): 1442-3. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12065271&dopt=Abstract

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Decreased point prevalence of Haemophilus influenzae type b (Hib) oropharyngeal colonization by mass immunization of Brazilian children less than 5 years old with hib polyribosylribitol phosphate polysaccharide-tetanus toxoid conjugate vaccine in combination with diphtheria-tetanus toxoids-pertussis vaccine. Author(s): Forleo-Neto E, de Oliveira CF, Maluf EM, Bataglin C, Araujo JM, Kunz LF Jr, Pustai AK, Vieira VS, Zanella RC, Brandileone MC, Mimica LM, Mimica IM. Source: The Journal of Infectious Diseases. 1999 October; 180(4): 1153-8. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10479142&dopt=Abstract

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Defective immune response to tetanus toxoid in hemodialysis patients and its association with diphtheria vaccination. Author(s): Kruger S, Seyfarth M, Sack K, Kreft B. Source: Vaccine. 1999 March 5; 17(9-10): 1145-50. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10195626&dopt=Abstract

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Deficiencies in tetanus prophylaxis in wound management in Ibadan, Nigeria. Author(s): Fatunde OJ, Familusi JB. Source: West Afr J Med. 2002 April-June; 21(2): 105-7. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12403028&dopt=Abstract

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Dendritic cell-based proliferative assays of peripheral T cell responses to tetanus toxoid. Author(s): Narendran P, Elsegood K, Leech NJ, Dayan CM. Source: Annals of the New York Academy of Sciences. 2002 April; 958: 170-4. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12021100&dopt=Abstract

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Detection of anti-tetanus antibodies in Turkish population. Author(s): Soyletir G, Yagci A, Topkaya A, Ciragil P. Source: Trop Doct. 1999 July; 29(3): 161-3. No Abstract Available. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10448241&dopt=Abstract

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Development of immunologic memory against tetanus toxoid and pertactin antigens from the diphtheria-tetanus-pertussis vaccine in atopic versus nonatopic children. Author(s): Holt PG, Rudin A, Macaubas C, Holt BJ, Rowe J, Loh R, Sly PD. Source: The Journal of Allergy and Clinical Immunology. 2000 June; 105(6 Pt 1): 1117-22. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10856144&dopt=Abstract

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Differences in female-male mortality after high-titre measles vaccine and association with subsequent vaccination with diphtheria-tetanus-pertussis and inactivated poliovirus: reanalysis of West African studies. Author(s): Aaby P, Jensen H, Samb B, Cisse B, Sodemann M, Jakobsen M, Poulsen A, Rodrigues A, Lisse IM, Simondon F, Whittle H. Source: Lancet. 2003 June 28; 361(9376): 2183-8. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12842371&dopt=Abstract

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Diminution of the anti-polyribosylribitol phosphate response to a combined diphtheria-tetanus-acellular pertussis/Haemophilus influenzae type b vaccine by concurrent inactivated poliovirus vaccination. Author(s): Rennels MB, Englund JA, Bernstein DI, Losonsky GA, Anderson EL, Pichichero ME, Munoz FM, Wolff MC. Source: The Pediatric Infectious Disease Journal. 2000 May; 19(5): 417-23. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10819337&dopt=Abstract

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Diphtheria and tetanus immunity. Author(s): Balestra DJ. Source: Annals of Internal Medicine. 2002 November 5; 137(9): 774-5; Author Reply 7745. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12416962&dopt=Abstract

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Diphtheria antitoxin levels among children primed with a diphtheria and tetanus toxoids and acellular pertussis vaccine lot with a subpotent diphtheria toxoid component. Author(s): Jackson LA, Falls S, Yu O, George J, Pietrobon PJ, Rubanowice D, Froeschle J. Source: The Journal of Infectious Diseases. 2001 June 1; 183(11): 1698-700. Epub 2001 May 09. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11343223&dopt=Abstract

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Diphtheria-tetanus-acellular pertussis vaccine adsorbed (Triacelluvax; DTaP3-CB): a review of its use in the prevention of Bordetella pertussis infection. Author(s): Matheson AJ, Goa KL. Source: Paediatric Drugs. 2000 March-April; 2(2): 139-59. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10937466&dopt=Abstract

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Does concomitant injection of a combined diphtheria-tetanus-acellular pertussis hepatitis B virus - inactivated polio virus vaccine influence the reactogenicity and immunogenicity of commercial Haemophilus influenzae type b conjugate vaccines? Author(s): Usonis V, Bakasenas V. Source: European Journal of Pediatrics. 1999 May; 158(5): 398-402. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10333123&dopt=Abstract

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Dose dependency of antibody response in infants and children to pneumococcal polysaccharides conjugated to tetanus toxoid. Author(s): Ahman H, Kayhty H, Vuorela A, Leroy O, Eskola J. Source: Vaccine. 1999 June 4; 17(20-21): 2726-32. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10418924&dopt=Abstract

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Down-regulation of IgE and IgG4 antibodies to tetanus toxoid and diphtheria toxoid by covaccination with cellular Bordetella pertussis vaccine. Author(s): Gruber C, Lau S, Dannemann A, Sommerfeld C, Wahn U, Aalberse RC. Source: Journal of Immunology (Baltimore, Md. : 1950). 2001 August 15; 167(4): 2411-7. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11490032&dopt=Abstract

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Duration of immunity to diphtheria and tetanus in young kidney transplant patients. Author(s): Pedrazzi C, Ghio L, Balloni A, Panuccio A, Foti M, Edefonti A, Assael BM. Source: Pediatric Transplantation. 1999 May; 3(2): 109-14. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10389132&dopt=Abstract

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Early responses to nonconjugated polyribosylribitol phosphate challenge as evidence of immune memory after combined diphtheria-tetanus-pertussis-polio-Haemophilus influenzae type b primary vaccination. Author(s): Dagan R, Amir J, Ashkenazi S, Hardt K, Kaufhold A. Source: The Pediatric Infectious Disease Journal. 2001 June; 20(6): 587-92. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11419500&dopt=Abstract

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Economic evaluation of use of diphtheria, tetanus, and acellular pertussis vaccine or diphtheria, tetanus, and whole-cell pertussis vaccine in the United States, 1997. Author(s): Ekwueme DU, Strebel PM, Hadler SC, Meltzer MI, Allen JW, Livengood JR. Source: Archives of Pediatrics & Adolescent Medicine. 2000 August; 154(8): 797-803. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10922276&dopt=Abstract

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Effect of transplacentally acquired tetanus antibodies on the antibody responses to Haemophilus influenzae type b-tetanus toxoid conjugate and tetanus toxoid vaccines in Filipino infants. Author(s): Nohynek H, Gustafsson L, Capeding MR, Kayhty H, Olander RM, Pascualk L, Ruutu P. Source: The Pediatric Infectious Disease Journal. 1999 January; 18(1): 25-30. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=9951976&dopt=Abstract

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Effect of warming adult diphtheria-tetanus vaccine on discomfort after injection: a randomised controlled trial. Author(s): Maiden MJ, Benton GN, Bourne RA. Source: The Medical Journal of Australia. 2003 May 5; 178(9): 433-6. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12720508&dopt=Abstract

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Effect on diphtheria immunity of combined tetanus and diphtheria booster vaccination in adults. Author(s): Marlovits S, Stocker R, Efstratiou A, Broughton K, Kaider A, Vecsei V, Kollaritsch H. Source: European Journal of Clinical Microbiology & Infectious Diseases : Official Publication of the European Society of Clinical Microbiology. 2000 July; 19(7): 506-13. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10968321&dopt=Abstract

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Effect on neonatal tetanus mortality after a culturally-based health promotion programme. Author(s): Meegan ME, Conroy RM, Lengeny SO, Renhault K, Nyangole J. Source: Lancet. 2001 August 25; 358(9282): 640-1. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11530155&dopt=Abstract

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Effects of a booster dose of tetanus toxoid after different primary courses of vaccination: implications on the use of immune globulin. Author(s): Bonaccorsi G, Papini D, Bonanni P, Lo Nostro A, Comodo N. Source: Ann Ig. 2001 January-February; 13(1): 3-10. No Abstract Available. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11305129&dopt=Abstract

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Effects of diphtheria-tetanus-pertussis or tetanus vaccination on allergies and allergyrelated respiratory symptoms among children and adolescents in the United States. Author(s): Hurwitz EL, Morgenstern H. Source: Journal of Manipulative and Physiological Therapeutics. 2000 February; 23(2): 81-90. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10714532&dopt=Abstract

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Elevated levels of maternal anti-tetanus toxin antibodies do not suppress the immune response to a Haemophilus influenzae type b polyribosylphosphate-tetanus toxoid conjugate vaccine. Author(s): Panpitpat C, Thisyakorn U, Chotpitayasunondh T, Furer E, Que JU, Hasler T, Cryz SJ Jr. Source: Bulletin of the World Health Organization. 2000; 78(3): 364-71. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10812736&dopt=Abstract

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Emergency treatment of tetanus. Author(s): Dastur FD. Source: J Assoc Physicians India. 1997; Suppl 2: 44-6. No Abstract Available. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11235617&dopt=Abstract

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Enhanced immunogenicity of hepatitis B surface antigen by insertion of a helper T cell epitope from tetanus toxoid. Author(s): Chengalvala MV, Bhat RA, Bhat BM, Vernon SK, Lubeck MD. Source: Vaccine. 1999 March 5; 17(9-10): 1035-41. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10195612&dopt=Abstract

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Epidemiology of tetanus in Italy in years 1971-2000. Author(s): Pedalino B, Cotter B, Ciofi degli Atti M, Mandolini D, Parroccini S, Salmaso S. Source: Euro Surveillance : Bulletin Europeen Sur Les Maladies Transmissibles = European Communicable Disease Bulletin. 2002 July; 7(7): 103-10. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12631930&dopt=Abstract

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Esmolol in a case of severe tetanus. Adequate haemodynamic control achieved despite markedly elevated catecholamine levels. Author(s): Beards SC, Lipman J, Bothma PA, Joynt GM. Source: S Afr J Surg. 1994 March; 32(1): 33-5. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11218441&dopt=Abstract

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Evaluation of a guinea pig model to assess interference in the immunogenicity of different components of a combination vaccine comprising diphtheria, tetanus and acellular pertussis (DTaP) vaccine and haemophilus influenzae type b capsular polysaccharide conjugate vaccine. Author(s): Gupta RK, Anderson R, Cecchini D, Rost B, Xu J, Gendreau K, Saroff DL, Marchant C, Siber GR. Source: Biologicals : Journal of the International Association of Biological Standardization. 1999 June; 27(2): 167-76. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10600208&dopt=Abstract

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Evaluation of a single dose of diphtheria-tetanus toxoids among adults in Odessa, Ukraine, 1995: immunogenicity and adverse reactions. Author(s): Golaz A, Hardy IR, Glushkevich TG, Areytchiuk EK, Deforest A, Strebel P, Wharton M, Sutter RW. Source: The Journal of Infectious Diseases. 2000 February; 181 Suppl 1: S203-7. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10657215&dopt=Abstract

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Evaluation of autonomic nervous system function with spectral analysis of heart rate variability in a case of tetanus. Author(s): Goto T, Fukushima H, Sasaki G, Matsuo N, Takahashi T. Source: Brain & Development. 2001 December; 23(8): 791-5. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11720795&dopt=Abstract

84

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Evaluation of De-O-acetylated meningococcal C polysaccharide-tetanus toxoid conjugate vaccine in infancy: reactogenicity, immunogenicity, immunologic priming, and bactericidal activity against O-acetylated and De-O-acetylated serogroup C strains. Author(s): Richmond P, Borrow R, Findlow J, Martin S, Thornton C, Cartwright K, Miller E. Source: Infection and Immunity. 2001 April; 69(4): 2378-82. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11254596&dopt=Abstract

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Evaluation of the national immunisation programme in the Netherlands: immunity to diphtheria, tetanus, poliomyelitis, measles, mumps, rubella and Haemophilus influenzae type b. Author(s): de Melker HE, van den Hof S, Berbers GA, Conyn-van Spaendonck MA. Source: Vaccine. 2003 January 30; 21(7-8): 716-20. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12531347&dopt=Abstract

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Evidence of efficacy of the Lederle/Takeda acellular pertussis component diphtheria and tetanus toxoids and pertussis vaccine but not the Lederle whole-cell component diphtheria and tetanus toxoids and pertussis vaccine against Bordetella parapertussis infection. Author(s): Heininger U, Stehr K, Christenson P, Cherry JD. Source: Clinical Infectious Diseases : an Official Publication of the Infectious Diseases Society of America. 1999 March; 28(3): 602-4. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10194085&dopt=Abstract

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Exacerbation of pemphigus foliaceus after tetanus vaccination accompanied by synthesis of auto-antibodies against paraneoplastic pemphigus antigens. Author(s): Korang K, Ghohestani R, Krieg T, Uitto J, Hunzelmann N. Source: Acta Dermato-Venereologica. 2002; 82(6): 482-3. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12575868&dopt=Abstract

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Experience of pediatric tetanus cases from Mumbai. Author(s): Tullu MS, Deshmukh CT, Kamat JR. Source: Indian Pediatrics. 2000 July; 37(7): 765-71. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10906810&dopt=Abstract

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Experience with diphtheria toxoid-tetanus toxoid-acellular pertussis vaccine in Japan. Author(s): Sato H, Sato Y. Source: Clinical Infectious Diseases : an Official Publication of the Infectious Diseases Society of America. 1999 June; 28 Suppl 2: S124-30. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10447030&dopt=Abstract

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Exposure risks and tetanus immunization in women of family owned farms. Implications for occupational and environmental health nursing. Author(s): Holland C, Carruth AK. Source: Aaohn Journal : Official Journal of the American Association of Occupational Health Nurses. 2001 March; 49(3): 130-6. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11760513&dopt=Abstract

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Extensive swelling after booster doses of acellular pertussis-tetanus-diphtheria vaccines. Author(s): Rennels MB, Deloria MA, Pichichero ME, Losonsky GA, Englund JA, Meade BD, Anderson EL, Steinhoff MC, Edwards KM. Source: Pediatrics. 2000 January; 105(1): E12. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10617749&dopt=Abstract

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Extensive swelling reactions occurring after booster doses of diphtheria-tetanusacellular pertussis vaccines. Author(s): Rennels MB. Source: Seminars in Pediatric Infectious Diseases. 2003 July; 14(3): 196-8. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12913831&dopt=Abstract

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Facial palsy of uncommon aetiology (cephalic tetanus). Author(s): Agarwal AK, Mudgerikar S, Sangla KS, Gogna A, Jain A. Source: J Assoc Physicians India. 1995 March; 43(3): 229-30. No Abstract Available. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11256922&dopt=Abstract

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Facilitating the WHO expanded program of immunization: the clinical profile of a combined diphtheria, tetanus, pertussis, hepatitis B and Haemophilus influenzae type b vaccine. Author(s): Aristegui J, Usonis V, Coovadia H, Riedemann S, Win KM, Gatchalian S, Bock HL. Source: International Journal of Infectious Diseases : Ijid : Official Publication of the International Society for Infectious Diseases. 2003 June; 7(2): 143-51. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12839717&dopt=Abstract

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Factors associated with missed opportunities to immunise with tetanus toxoid at a tertiary health institution in Nigeria. Author(s): Edet EE, Ikpeme BM, Ndifon WO, Oyo-Ita AE. Source: Cent Afr J Med. 1998 August; 44(8): 199-202. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10101419&dopt=Abstract

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Factors associated with TT (tetanus toxoid) immunization among pregnant women, in Saparua, Maluku, Indonesia. Author(s): Roosihermiatie B, Nishiyama M, Nakae K. Source: Southeast Asian J Trop Med Public Health. 2000 March; 31(1): 91-5. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11023073&dopt=Abstract

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Fatal tetanus in a drug abuser with “protective” antitetanus antibodies. Author(s): Abrahamian FM, Pollack CV Jr, LoVecchio F, Nanda R, Carlson RW. Source: The Journal of Emergency Medicine. 2000 February; 18(2): 189-93. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10699520&dopt=Abstract

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Feasibility studies of large scale production of human anti-tetanus toxoid monoclonal antibodies. Author(s): Martial-Gros A, Sarin KK, Mukhopadhyay A, Ghosh S. Source: Journal of Biotechnology. 1999 January 22; 67(2-3): 205-16. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=9990734&dopt=Abstract

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Fifth vaccination with dipthteria, tetanus and acellular pertussis is beneficial in fourto six-year-olds. Author(s): Pichichero ME, Anderson EL, Rennels MB, Edwards KM, England JA. Source: The Pediatric Infectious Disease Journal. 2001 April; 20(4): 427-33. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11332669&dopt=Abstract

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Functional antibodies elicited by an 11-valent diphtheria-tetanus toxoid-conjugated pneumococcal vaccine. Author(s): Puumalainen T, Ekstrom N, Zeta-Capeding R, Ollgren J, Jousimies K, Lucero M, Nohynek H, Kayhty H. Source: The Journal of Infectious Diseases. 2003 June 1; 187(11): 1704-8. Epub 2003 May 09. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12751027&dopt=Abstract

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Functional antibody activity elicited by fractional doses of Haemophilus influenzae type b conjugate vaccine (polyribosylribitol phosphate-tetanus toxoid conjugate). Author(s): Romero-Steiner S, Fernandez J, Biltoft C, Wohl ME, Sanchez J, Feris J, Balter S, Levine OS, Carlone GM. Source: Clinical and Diagnostic Laboratory Immunology. 2001 November; 8(6): 1115-9. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11687449&dopt=Abstract

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Gelatin-containing diphtheria-tetanus-pertussis (DTP) vaccine causes sensitization to gelatin in the recipients. Author(s): Kumagai T, Ozaki T, Kamada M, Igarashi C, Yuri K, Furukawa H, Wagatuma K, Chiba S, Sato M, Kojima H, Saito A, Okui T, Yano S. Source: Vaccine. 2000 February 14; 18(15): 1555-61. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10618554&dopt=Abstract

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Generalized tetanus in a patient with a diabetic foot infection. Author(s): Panning CA, Bayat M. Source: Pharmacotherapy. 1999 July; 19(7): 885-90. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10417039&dopt=Abstract

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Granuloma annulare possibly triggered by antitetanus vaccination. Author(s): Baykal C, Ozkaya-Bayazit E, Kaymaz R. Source: Journal of the European Academy of Dermatology and Venereology : Jeadv. 2002 September; 16(5): 516-8. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12428851&dopt=Abstract

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Greater antibody responses to an eleven valent mixed carrier diphtheria- or tetanusconjugated pneumococcal vaccine in Filipino than in Finnish or Israeli infants. Author(s): Puumalainen T, Dagan R, Wuorimaa T, Zeta-Capeding R, Lucero M, Ollgren J, Kayhty H, Nohynek H. Source: The Pediatric Infectious Disease Journal. 2003 February; 22(2): 141-9. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12586978&dopt=Abstract

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Haemophilus influenzae type B (Hib) antibody responses in children given diphtheria-tetanus-acellular pertussis-Hib combination vaccines. Author(s): Finn A, Blondeau C, Bell F. Source: The Journal of Infectious Diseases. 2000 June; 181(6): 2117-8. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10837208&dopt=Abstract

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Haemophilus influenzae type b conjugate vaccine diluted tenfold in diphtheriatetanus-whole cell pertussis vaccine: a randomized trial. Author(s): Nicol M, Huebner R, Mothupi R, Kayhty H, Mbelle N, Khomo E. Source: The Pediatric Infectious Disease Journal. 2002 February; 21(2): 138-41. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11840081&dopt=Abstract

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Haemophilus influenzae type b disease: impact and effectiveness of diphtheriatetanus toxoids-acellular pertussis (-inactivated poliovirus)/H. influenzae type b combination vaccines. Author(s): Schmitt HJ, von Kries R, Hassenpflug B, Hermann M, Siedler A, Niessing W, Clemens R, Weil J. Source: The Pediatric Infectious Disease Journal. 2001 August; 20(8): 767-74. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11734739&dopt=Abstract

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Hepatitis B surface antigen- and tetanus toxoid-specific clonal expansion of CD4+ cells in vitro determined by TCRBV CDR3 length and nucleotide sequence. Author(s): Uko GP, Fraser PA, Awdeh ZL, Fici DA, Crawford KD, Larsen CE, Alper CA. Source: Genes and Immunity. 2001 February; 2(1): 11-9. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11294562&dopt=Abstract

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Heterogeneity in diphtheria-tetanus-acellular pertussis vaccine-specific cellular immunity during infancy: relationship to variations in the kinetics of postnatal maturation of systemic th1 function. Author(s): Rowe J, Macaubas C, Monger T, Holt BJ, Harvey J, Poolman JT, Loh R, Sly PD, Holt PG. Source: The Journal of Infectious Diseases. 2001 July 1; 184(1): 80-8. Epub 2001 May 29. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11398113&dopt=Abstract

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How botulinum and tetanus neurotoxins block neurotransmitter release. Author(s): Humeau Y, Doussau F, Grant NJ, Poulain B. Source: Biochimie. 2000 May; 82(5): 427-46. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10865130&dopt=Abstract

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Human anti-FcepsilonRIalpha autoantibodies isolated from healthy donors crossreact with tetanus toxoid. Author(s): Horn MP, Gerster T, Ochensberger B, Derer T, Kricek F, Jouvin MH, Kinet JP, Tschernig T, Vogel M, Stadler BM, Miescher SM. Source: European Journal of Immunology. 1999 April; 29(4): 1139-48. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10229080&dopt=Abstract

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Human onchocerciasis and tetanus vaccination: impact on the postvaccination antitetanus antibody response. Author(s): Cooper PJ, Espinel I, Wieseman M, Paredes W, Espinel M, Guderian RH, Nutman TB. Source: Infection and Immunity. 1999 November; 67(11): 5951-7. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10531253&dopt=Abstract

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Humoral immunity against diphtheria, tetanus and poliomyelitis after antineoplastic therapy in children and adolescents--a retrospective analysis. Author(s): von der Hardt K, Jungert J, Beck JD, Heininger U. Source: Vaccine. 2000 July 1; 18(26): 2999-3004. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10825602&dopt=Abstract

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Hypoxemic acute respiratory failure of severe tetanus: is it of cardiac or pulmonary origin? Author(s): Khajehdehi P, Rezaian GR. Source: Intensive Care Medicine. 2001 May; 27(5): 938. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11430556&dopt=Abstract

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Identification of novel small molecules that bind to two different sites on the surface of tetanus toxin C fragment. Author(s): Cosman M, Lightstone FC, Krishnan VV, Zeller L, Prieto MC, Roe DC, Balhorn R. Source: Chemical Research in Toxicology. 2002 October; 15(10): 1218-28. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12387617&dopt=Abstract

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Identification of risk factors for death from tetanus in Pernambuco, Brazil: a casecontrol study. Author(s): Miranda-Filho DB, Ximenes RA, Bernardino SN, Escariao AG. Source: Revista Do Instituto De Medicina Tropical De Sao Paulo. 2000 NovemberDecember; 42(6): 333-9. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11136520&dopt=Abstract

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Immediate allergy to tetanus toxoid vaccine: determination of immunoglobulin E and immunoglobulin G antibodies to allergenic proteins. Author(s): Mayorga C, Torres MJ, Corzo JL, Alvarez J, Garcia JA, Rodriguez CA, Blanca M, Jurado A. Source: Annals of Allergy, Asthma & Immunology : Official Publication of the American College of Allergy, Asthma, & Immunology. 2003 February; 90(2): 238-43. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12602673&dopt=Abstract

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Immune response of premature infants to meningococcal serogroup C and combined diphtheria-tetanus toxoids-acellular pertussis-Haemophilus influenzae type b conjugate vaccines. Author(s): Slack MH, Schapira D, Thwaites RJ, Burrage M, Southern J, Andrews N, Borrow R, Goldblatt D, Miller E. Source: The Journal of Infectious Diseases. 2001 December 15; 184(12): 1617-20. Epub 2001 Dec 03. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11740740&dopt=Abstract

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Immune response to a diphtheria and tetanus toxoid administration in a three-dose diphtheria tetanus whole-cell pertussis/enhanced inactivated poliovirus vaccination schedule: a 7-year follow up. Author(s): Swartz TA, Saliou P, Catznelson E, Blondeau C, Gil I, Peled T, Havkin O, Fletcher M. Source: European Journal of Epidemiology. 2003; 18(8): 827-33. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12974560&dopt=Abstract

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Immune response to octavalent diphtheria- and tetanus-conjugated pneumococcal vaccines is serotype- and carrier-specific: the choice for a mixed carrier vaccine. Author(s): Sigurdardottir ST, Ingolfsdottir G, Davidsdottir K, Gudnason T, Kjartansson S, Kristinsson KG, Bailleux F, Leroy O, Jonsdottir I. Source: The Pediatric Infectious Disease Journal. 2002 June; 21(6): 548-54. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12182380&dopt=Abstract

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Immunity against diphtheria and tetanus in German blood donors. Author(s): Aue A, Hennig H, Kruger S, Closius B, Kirchner H, Seyfarth M. Source: Medical Microbiology and Immunology. 2003 May; 192(2): 93-7. Epub 2002 November 30. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12736822&dopt=Abstract

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Immunity to tetanus among adults in Turkey. Author(s): Ergonul O, Sozen T, Tekeli E. Source: Scandinavian Journal of Infectious Diseases. 2001; 33(10): 728-30. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11728035&dopt=Abstract

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Immunity to tetanus in male adults in Dar es Salaam, Tanzania. Author(s): Aboud S, Lyamuya EF, Kristoffersen EK, Matre R. Source: East Afr Med J. 2002 February; 79(2): 73-6. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12380880&dopt=Abstract

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Immunization of pregnant women with group B streptococcal type III capsular polysaccharide-tetanus toxoid conjugate vaccine. Author(s): Baker CJ, Rench MA, McInnes P. Source: Vaccine. 2003 July 28; 21(24): 3468-72. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12850362&dopt=Abstract

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Immunization with recombinant Streptococcus gordonii expressing tetanus toxin fragment C confers protection from lethal challenge in mice. Author(s): Medaglini D, Ciabattini A, Spinosa MR, Maggi T, Marcotte H, Oggioni MR, Pozzi G. Source: Vaccine. 2001 February 28; 19(15-16): 1931-9. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11228363&dopt=Abstract

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Immunizing adults against tetanus and diphtheria. Author(s): Scott J, Hickey J. Source: Can Fam Physician. 2003 May; 49: 587-8. No Abstract Available. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12790269&dopt=Abstract

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Immunogenicity and reactogenicity of a single dose of a diphtheria--tetanus--acellular pertussis component vaccine (DTaP) compared to a diphtheria--tetanus toxoid (Td) and a diphtheria toxoid vaccine (d) in adults. Author(s): Bartels I, Jungert J, Lugauer S, Stehr K, Heininger U. Source: Vaccine. 2001 April 30; 19(23-24): 3137-45. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11312009&dopt=Abstract

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Immunogenicity and reactogenicity of acellular diphtheria/tetanus/pertussis vaccines given as a pre-school booster: effect of simultaneous administration of MMR. Author(s): Miller E, Waight P, Laurichesse H, Andrews N, Thornton C, Sesardic D, Corbel M. Source: Vaccine. 2001 July 16; 19(28-29): 3904-11. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11427264&dopt=Abstract

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Immunogenicity and reactogenicity of diphtheria, tetanus and pertussis toxoids combined with inactivated polio vaccine, when administered concomitantly with or as a diluent for a Hib conjugate vaccine. Author(s): Knutsson N, Trollfors B, Taranger J, Bergfors E, Sundh V, Lagergard T, Ostergaard E, Cicirello H, Kayhty H. Source: Vaccine. 2001 August 14; 19(31): 4396-403. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11483264&dopt=Abstract

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Immunogenicity and reactogenicity of the adult tetanus-diphtheria vaccine. How many doses are necessary? Author(s): Bayas JM, Vilella A, Bertran MJ, Vidal J, Batalla J, Asenjo MA, Salleras LL. Source: Epidemiology and Infection. 2001 December; 127(3): 451-60. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11811878&dopt=Abstract

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Immunogenicity of a Haemophilus influenzae type b-tetanus toxoid conjugate vaccine when mixed with a diphtheria-tetanus-acellular pertussis-hepatitis B combination vaccine. Author(s): Greenberg DP, Wong VK, Partridge S, Chang SJ, Jing J, Howe BJ, Ward JI. Source: The Pediatric Infectious Disease Journal. 2000 December; 19(12): 1135-40. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11144372&dopt=Abstract

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Immunogenicity of, and immunologic memory to, a reduced primary schedule of meningococcal C-tetanus toxoid conjugate vaccine in infants in the United kingdom. Author(s): Borrow R, Goldblatt D, Finn A, Southern J, Ashton L, Andrews N, Lal G, Riley C, Rahim R, Cartwright K, Allan G, Miller E. Source: Infection and Immunity. 2003 October; 71(10): 5549-55. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=14500473&dopt=Abstract

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Immunologic and virologic response after tetanus toxoid booster among HIV-1- and HIV-2-infected Senegalese individuals. Author(s): Dieye TN, Sow PS, Simonart T, Gueye-Ndiaye A, Popper SJ, Delforge ML, Dieye A, Sarr AD, Crusiaux A, Van Vooren JP, Devleeschouwer M, Kanki P, Mboup S, Diakhate L, Farber CM. Source: Vaccine. 2001 December 12; 20(5-6): 905-13. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11738756&dopt=Abstract

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Immunologic response to a single dose of tetanus toxoid in older people. Author(s): Shohat T, Marva E, Sivan Y, Lerman I, Mates A, Cohen A. Source: Journal of the American Geriatrics Society. 2000 August; 48(8): 949-51. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10968300&dopt=Abstract

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Impact of a birth dose of hepatitis B vaccine on the reactogenicity and immunogenicity of diphtheria-tetanus-acellular pertussis-hepatitis B-inactivated poliovirus-Haemophilus influenzae type b combination vaccination. Author(s): Pichichero ME, Blatter MM, Reisinger KS, Harrison CJ, Johnson CE, Steinhoff MC, Senders SD, Rothstein EP, Willems P, Howe BJ. Source: The Pediatric Infectious Disease Journal. 2002 September; 21(9): 854-9. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12352809&dopt=Abstract

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Impact of guidelines to alter antitetanus prophylaxis practices and reduce costs in the emergency department. Author(s): Elkharrat D, Boyer Chammard A, Raskine L, Durand-Zaleski I, Zerbani A, Caulin C, Chastang C. Source: American Journal of Therapeutics. 1999 July; 6(4): 203-9. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11329098&dopt=Abstract

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Impact of vaccine shortage on diphtheria and tetanus toxoids and acellular pertussis vaccine coverage rates among children aged 24 months--Puerto Rico, 2002. Author(s): Rivera A, Orengo JC, Rivera AL, Rodriguez C, Calderon E, Rullan J, Yusuf H, Rodewald L. Source: Mmwr. Morbidity and Mortality Weekly Report. 2002 August 2; 51(30): 667-8. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12197213&dopt=Abstract

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Incidence of and risk factors for nosocomial pneumonia in patients with tetanus. Author(s): Cavalcante NJ, Sandeville ML, Medeiros EA. Source: Clinical Infectious Diseases : an Official Publication of the Infectious Diseases Society of America. 2001 December 1; 33(11): 1842-6. Epub 2001 October 19. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11668432&dopt=Abstract

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Increased levels of specific leukocyte- and platelet-derived substances during normal anti-tetanus antibody synthesis in patients with inactive Crohn disease. Author(s): Nielsen HJ, Mortensen T, Holten-Andersen M, Brunner N, Sorensen S, RaskMadsen J. Source: Scandinavian Journal of Gastroenterology. 2001 March; 36(3): 265-9. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11305513&dopt=Abstract

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Induction of cross-reactive antibodies by immunization of healthy adults with types Ia and Ib group B streptococcal polysaccharide-tetanus toxoid conjugate vaccines. Author(s): Brigtsen AK, Kasper DL, Baker CJ, Jennings HJ, Guttormsen HK. Source: The Journal of Infectious Diseases. 2002 May 1; 185(9): 1277-84. Epub 2002 April 03. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12001045&dopt=Abstract

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Induction of immunologic tolerance to tetanus toxoid by anti-human CD4 in HLADR3(+)/human CD4(+)/murine CD4(-) multiple transgenic mice. Author(s): Laub R, Dorsch M, Wenk K, Emmrich F. Source: Transplantation Proceedings. 2001 May; 33(3): 2182-3. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11377495&dopt=Abstract

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Influence of placental malaria infection and maternal hypergammaglobulinaemia on materno-foetal transfer of measles and tetanus antibodies in a rural west African population. Author(s): Okoko BJ, Wesuperuma LH, Ota MO, Banya WA, Pinder M, Gomez FS, Osinusi K, Hart AC. Source: J Health Popul Nutr. 2001 June; 19(2): 59-65. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11503348&dopt=Abstract

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Influenza, pneumococcal, and tetanus toxioid vaccination of adults--United States, 1993-7. Author(s): Singleton JA, Greby SM, Wooten KG, Walker FJ, Strikas R. Source: Mmwr. Cdc Surveillance Summaries : Morbidity and Mortality Weekly Report. Cdc Surveillance Summaries / Centers for Disease Control. 2000 September 22; 49(9): 3962. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11016877&dopt=Abstract

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Interaction of tetanus toxin derived hybrid proteins with neuronal cells. Author(s): Figueiredo DM, Matthews CC, Parks DA, Fairweather NF, Dougan G, Wilt SG, Fishman PS. Source: Journal of Natural Toxins. 2000 November; 9(4): 363-79. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11126515&dopt=Abstract

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Interchangeability of 2 diphtheria-tetanus-acellular pertussis vaccines in infancy. Author(s): Greenberg DP, Pickering LK, Senders SD, Bissey JD, Howard RA, Blatter MM, Reisinger K, Pichichero ME, Howe BJ. Source: Pediatrics. 2002 April; 109(4): 666-72. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11927713&dopt=Abstract

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Intranasal vaccination against plague, tetanus and diphtheria. Author(s): Alpar HO, Eyles JE, Williamson ED, Somavarapu S. Source: Advanced Drug Delivery Reviews. 2001 September 23; 51(1-3): 173-201. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11516788&dopt=Abstract

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Intrathecal baclofen for severe tetanus in a pregnant woman. Author(s): Engrand N, Van De Perre P, Vilain G, Benhamou D. Source: European Journal of Anaesthesiology. 2001 April; 18(4): 261-3. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11350465&dopt=Abstract

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Intrathecal immunoglobulin in tetanus. Author(s): Tullu MS, Deshmukh CT. Source: Indian Pediatrics. 2003 February; 40(2): 176-7; Author Reply 177-8. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12626840&dopt=Abstract

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Intrathecal immunoglobulin in the treatment of tetanus. Author(s): Menon J, Mathews L. Source: Indian Pediatrics. 2002 July; 39(7): 654-7. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12147891&dopt=Abstract

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Issues related to the decennial tetanus-diphtheria toxoid booster recommendations in adults. Author(s): Gardner P. Source: Infectious Disease Clinics of North America. 2001 March; 15(1): 143-53, Ix-X. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11301812&dopt=Abstract

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Kinetics of booster responses to Haemophilus influenzae type B conjugate after combined diphtheria-tetanus-acelluar pertussis-Haemophilus influenzae type b vaccination in infants. Author(s): Pichichero ME, Voloshen T, Passador S. Source: The Pediatric Infectious Disease Journal. 1999 December; 18(12): 1106-8. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10608637&dopt=Abstract

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Knowledge, attitudes and practices of general practitioners in Karachi District Central about tetanus immunization in adults. Author(s): Ahmed SI, Baig L, Thaver IH, Siddiqui MI, Jafery SI, Javed A. Source: J Pak Med Assoc. 2001 October; 51(10): 367-9. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11768940&dopt=Abstract

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Lack of consistent relationship between quantity of aluminum in diphtheria-tetanusacellular pertussis vaccines and rates of extensive swelling reactions. Author(s): Rennels MB, Deloria MA, Pichichero ME, Englund JA, Anderson EL, Steinhoff MC, Decker MD, Edwards KM. Source: Vaccine. 2002 May 31; 20 Suppl 3: S44-7. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12184364&dopt=Abstract

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Lessons from a case of tetanus in an elderly woman. Author(s): Kwan J, Lim S, Allen SC. Source: Postgraduate Medical Journal. 1999 October; 75(888): 631-3. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10621914&dopt=Abstract

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Levels and avidity of antibodies to tetanus toxoid in children aged 1-15 years in Dar es Salaam and Bagamoyo, Tanzania. Author(s): Aboud S, Matre R, Lyamuya EF, Kristoffersen EK. Source: Annals of Tropical Paediatrics. 2000 December; 20(4): 313-22. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11219170&dopt=Abstract

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Levels of antibodies specific to tetanus toxoid, Haemophilus influenzae type b, and pneumococcal capsular polysaccharide in healthy children and adults. Author(s): Schauer U, Stemberg F, Rieger CH, Buttner W, Borte M, Schubert S, Mollers H, Riedel F, Herz U, Renz H, Herzog W. Source: Clinical and Diagnostic Laboratory Immunology. 2003 March; 10(2): 202-7. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12626443&dopt=Abstract

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Local reactions and IgE antibodies to pertussis toxin after acellular diphtheriatetanus-pertussis immunization. Author(s): Edelman K, Malmstrom K, He Q, Savolainen J, Terho EO, Mertsola J. Source: European Journal of Pediatrics. 1999 December; 158(12): 989-94. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10592076&dopt=Abstract

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Localized tetanus in a child. Author(s): Fiorillo L, Robinson JL. Source: Annals of Emergency Medicine. 1999 April; 33(4): 460-3. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10092728&dopt=Abstract

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Longitudinal analysis of T cells responding to tetanus toxoid in healthy subjects as well as in pediatric patients after bone marrow transplantation: the identification of identical TCR-CDR3 regions in time suggests long-term stability of at least part of the antigen-specific TCR repertoire. Author(s): Godthelp BC, van Tol MJ, Vossen JM, van den Elsen PJ. Source: International Immunology. 2001 April; 13(4): 507-18. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11282990&dopt=Abstract

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Long-term pertussis-specific immune responses to a combined diphtheria, tetanus, tricomponent acellular pertussis and hepatitis B vaccine in pre-term infants. Author(s): Esposito S, Faldella G, Giammanco A, Bosis S, Friscia O, Clerici M, Principi N. Source: Vaccine. 2002 July 26; 20(23-24): 2928-32. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12126904&dopt=Abstract

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Long-term pertussis-specific immunity after primary vaccination with a combined diphtheria, tetanus, tricomponent acellular pertussis, and hepatitis B vaccine in comparison with that after natural infection. Author(s): Esposito S, Agliardi T, Giammanco A, Faldella G, Cascio A, Bosis S, Friscia O, Clerici M, Principi N. Source: Infection and Immunity. 2001 July; 69(7): 4516-20. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11401994&dopt=Abstract

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Long-term recurrent infection of tetanus in an elderly patient. Author(s): Kimura F, Sasaki N, Uehara H. Source: The American Journal of Emergency Medicine. 2001 March; 19(2): 168. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11239268&dopt=Abstract

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Looking back: case of traumatic tetanus--recovery. 1885. Author(s): Ward BF. Source: J Miss State Med Assoc. 2003 February; 44(2): 48-50. No Abstract Available. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12703147&dopt=Abstract

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Lymphocyte response to tetanus toxin T-cell epitopes: effects of tetanus vaccination and concurrent malaria prophylaxis. Author(s): Fryauff DJ, Mouzin E, Church LW, Ratiwayanto S, Hadiputranto H, Sutamihardja MA, Widjaja H, Corradin G, Subianto B, Hoffman SL. Source: Vaccine. 1999 January; 17(1): 59-63. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10078608&dopt=Abstract

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Magnesium as first line therapy in the management of tetanus: a prospective study of 40 patients. Author(s): Attygalle D, Rodrigo N. Source: Anaesthesia. 2002 August; 57(8): 811-7. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12133096&dopt=Abstract

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Magnesium sulphate as a first line therapy in the management of tetanus. Author(s): Thwaites CL, Farrar JJ. Source: Anaesthesia. 2003 March; 58(3): 286. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12603464&dopt=Abstract

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Magnesium sulphate for the control of spasms in severe tetanus. Author(s): Attygalle D, Rodrigo N. Source: Anaesthesia. 1999 March; 54(3): 302-3. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10364881&dopt=Abstract

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Magnitude of interference after diphtheria-tetanus toxoids-acellular pertussis/Haemophilus influenzae type b capsular polysaccharide-tetanus vaccination is related to the number of doses administered. Author(s): Daum RS, Zenko CE, Given GZ, Ballanco GA, Parikh H, Germino K. Source: The Journal of Infectious Diseases. 2001 November 15; 184(10): 1293-9. Epub 2001 October 15. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11679918&dopt=Abstract

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Management and prevention of tetanus. Author(s): Edlich RE, Hill LG, Mahler CA, Cox MJ, Becker DG, Horowitz JH, Nichter LS, Martin ML, Lineweaver WC. Source: Journal of Long-Term Effects of Medical Implants. 2003; 13(3): 139-54. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=14516181&dopt=Abstract

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Management of sympathetic overactivity in tetanus with epidural bupivacaine and sufentanil: experience with 11 patients. Author(s): Bhagwanjee S, Bosenberg AT, Muckart DJ. Source: Critical Care Medicine. 1999 September; 27(9): 1721-5. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10507589&dopt=Abstract

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Mass psychogenic illness following tetanus-diphtheria toxoid vaccination in Jordan. Author(s): Kharabsheh S, Al-Otoum H, Clements J, Abbas A, Khuri-Bulos N, Belbesi A, Gaafar T, Dellepiane N. Source: Bulletin of the World Health Organization. 2001; 79(8): 764-70. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11545334&dopt=Abstract

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Neonatal tetanus associated with topical umbilical ghee: covert role of cow dung. Author(s): Bennett J, Ma C, Traverso H, Agha SB, Boring J. Source: International Journal of Epidemiology. 1999 December; 28(6): 1172-5. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10661665&dopt=Abstract

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Neonatal tetanus elimination in Mpumalanga Province, South Africa. Author(s): Idema CD, Harris BN, Ogunbanjo GA, Durrheim DN. Source: Tropical Medicine & International Health : Tm & Ih. 2002 July; 7(7): 622-4. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12100446&dopt=Abstract

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Neonatal tetanus in Awassa: retrospective analysis of patients admitted over 5 years. Author(s): Nida H. Source: Ethiop Med J. 2001 July; 39(3): 241-6. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11921554&dopt=Abstract

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Neonatal tetanus in Port Harcourt. Author(s): Oruamabo RS, Igbagiri FP. Source: Afr J Med Med Sci. 1996 September; 25(3): 265-8. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10457803&dopt=Abstract

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Neonatal tetanus in Serbia from 1968 through 1997. Author(s): Jarebinski M, Pekmezovic T, Pavlovic M, Pantovic V, Acimovic A. Source: The Pediatric Infectious Disease Journal. 2002 November; 21(11): 1092-3. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12442034&dopt=Abstract

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Neonatal tetanus in the middle Black Sea region of Turkey. Author(s): Totan M, Kucukoduk S, Dagdemir A, Dilber C. Source: Turk J Pediatr. 2002 April-June; 44(2): 139-41. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12026202&dopt=Abstract

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Neonatal tetanus in the southeast of Turkey: risk factors, and clinical and prognostic aspects. Review of 73 cases, 1990-1999. Author(s): Yaramis A, Tas MA. Source: Turk J Pediatr. 2000 October-December; 42(4): 272-4. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11196740&dopt=Abstract

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Neonatal tetanus. Author(s): Renge RL, Patel AB. Source: Indian Pediatrics. 2001 November; 38(11): 1316. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11721078&dopt=Abstract

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Neonatal tetanus. Author(s): Prevots DR. Source: Bulletin of the World Health Organization. 1998; 76 Suppl 2: 135-6. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10063693&dopt=Abstract

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Neonatal tetanus: a continuing challenge in the southeast of Turkey: risk factors, clinical features and prognostic factors. Author(s): Gurkan F, Bosnak M, Dikici B, Bosnak V, Tas MA, Haspolat K, Kara IH, Ozkan I. Source: European Journal of Epidemiology. 1999 February; 15(2): 171-4. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10204647&dopt=Abstract

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Neonatal tetanus: mortality rate and risk factors in Loralai District, Pakistan. Author(s): Quddus A, Luby S, Rahbar M, Pervaiz Y. Source: International Journal of Epidemiology. 2002 June; 31(3): 648-53. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12055169&dopt=Abstract

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Neuronal targeting of cardiotrophin-1 by coupling with tetanus toxin C fragment. Author(s): Bordet T, Castelnau-Ptakhine L, Fauchereau F, Friocourt G, Kahn A, Haase G. Source: Molecular and Cellular Neurosciences. 2001 May; 17(5): 842-54. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11358482&dopt=Abstract

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Neurosurgical treatment for tetanus. Author(s): Wilson E. Source: Journal of the History of the Neurosciences. 1997 April; 6(1): 82-5. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11619200&dopt=Abstract

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Notice to readers: deferral of routine booster doses of tetanus and diphtheria toxoids for adolescents and adults. Author(s): Kaye D. Source: Clinical Infectious Diseases : an Official Publication of the Infectious Diseases Society of America. 2001 July 15; 33(2): Iii-Iv. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11474631&dopt=Abstract

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Otolaryngologic aspects of tetanus. Author(s): Aydin K, Caylan R, Caylan R, Bektas D, Koksal I. Source: Eur Arch Otorhinolaryngol. 2003 January;260(1):52-6. Epub 2002 August 10. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12520358&dopt=Abstract

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Pemphigus following tetanus and diphtheria vaccination. Author(s): Cozzani E, Cacciapuoti M, Parodi A, Rebora A. Source: The British Journal of Dermatology. 2002 July; 147(1): 188-9. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12154773&dopt=Abstract

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Pharmacotherapy of tetanus--a review. Author(s): Reddy VG. Source: Middle East J Anesthesiol. 2002 February; 16(4): 419-42. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11949205&dopt=Abstract

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Phase 1 and phase 2 studies of Salmonella enterica serovar paratyphi A O-specific polysaccharide-tetanus toxoid conjugates in adults, teenagers, and 2- to 4-year-old children in Vietnam. Author(s): Konadu EY, Lin FY, Ho VA, Thuy NT, Van Bay P, Thanh TC, Khiem HB, Trach DD, Karpas AB, Li J, Bryla DA, Robbins JB, Szu SC. Source: Infection and Immunity. 2000 March; 68(3): 1529-34. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10678970&dopt=Abstract

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Phase I trial of a melanoma vaccine with gp100(280-288) peptide and tetanus helper peptide in adjuvant: immunologic and clinical outcomes. Author(s): Slingluff CL Jr, Yamshchikov G, Neese P, Galavotti H, Eastham S, Engelhard VH, Kittlesen D, Deacon D, Hibbitts S, Grosh WW, Petroni G, Cohen R, Wiernasz C, Patterson JW, Conway BP, Ross WG. Source: Clinical Cancer Research : an Official Journal of the American Association for Cancer Research. 2001 October; 7(10): 3012-24. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11595689&dopt=Abstract

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Phase I trial of two recombinant vaccines containing the 19kd carboxy terminal fragment of Plasmodium falciparum merozoite surface protein 1 (msp-1(19)) and T helper epitopes of tetanus toxoid. Author(s): Keitel WA, Kester KE, Atmar RL, White AC, Bond NH, Holland CA, Krzych U, Palmer DR, Egan A, Diggs C, Ballou WR, Hall BF, Kaslow D. Source: Vaccine. 1999 October 14; 18(5-6): 531-9. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10519944&dopt=Abstract

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Philosophic objection to vaccination as a risk for tetanus among children younger than 15 years. Author(s): Fair E, Murphy TV, Golaz A, Wharton M. Source: Pediatrics. 2002 January; 109(1): E2. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11773570&dopt=Abstract

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Poor response to hib (PRP-T) vaccine when combined with an acellular pertussis/diphtheria/tetanus vaccine for primary immunization of infants. Author(s): Bell F, Health P, Shackley F, Maclennan J, Herbert M, Shearstone N, Diggle L, Moxon ER, Finn A. Source: Biologicals : Journal of the International Association of Biological Standardization. 1999 June; 27(2): 113. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10600197&dopt=Abstract

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Post-neonatal tetanus: issues in intensive care management. Author(s): Singhi S, Jain V, Subramanian C. Source: Indian J Pediatr. 2001 March; 68(3): 267-72. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11338225&dopt=Abstract

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Postoperative tetanus: a case report. Author(s): Katz KC, Walmsley SL. Source: Cmaj : Canadian Medical Association Journal = Journal De L'association Medicale Canadienne. 2000 September 5; 163(5): 571-3. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11006769&dopt=Abstract

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Prevalence of tetanus immunity in the Egyptian population. Author(s): Redwan el-RM, Al-Awady MK. Source: Human Antibodies. 2002; 11(1-2): 55-9. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12237476&dopt=Abstract

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Preventing and treating tetanus. Author(s): Thwaites CL, Farrar JJ. Source: Bmj (Clinical Research Ed.). 2003 January 18; 326(7381): 117-8. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12531822&dopt=Abstract

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Primary vaccination of infants with diphtheria-tetanus-acellular pertussis-hepatitis B virus- inactivated polio virus and Haemophilus influenzae type b vaccines given as either separate or mixed injections. Author(s): Schmitt HJ, Knuf M, Ortiz E, Sanger R, Uwamwezi MC, Kaufhold A. Source: The Journal of Pediatrics. 2000 September; 137(3): 304-12. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10969252&dopt=Abstract

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Priming effect, immunogenicity and safety of an Haemophilus influenzae type btetanus toxoid conjugate (PRP-T) and diphtheria-tetanus-acellular pertussis (DTaP) combination vaccine administered to infants in Belgium and Turkey. Author(s): Hoppenbrouwers K, Kanra G, Roelants M, Ceyhan M, Vandermeulen C, Yurdakok K, Silier T, Dupuy M, Pehlivan T, Ozmert E, Desmyter J. Source: Vaccine. 1999 February 26; 17(7-8): 875-86. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10067694&dopt=Abstract

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Production of neutralizing human monoclonal antibody directed to tetanus toxin in CHO cell. Author(s): Chin J, Sohn Y, Lee SH, Park YI, Choi MJ. Source: Biologicals : Journal of the International Association of Biological Standardization. 2003 March; 31(1): 45-53. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12623059&dopt=Abstract

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Quality control of diphtheria tetanus acellular pertussis combined (DTaP) vaccines in Japan. Author(s): Horiuchi Y, Takahashi M, Konda T, Ochiai M, Yamamoto A, Kataoka M, Toyoizumi H, Arakawa Y. Source: Japanese Journal of Infectious Diseases. 2001 October; 54(5): 167-80. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11754154&dopt=Abstract

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Questions and answers. How do I know if I need a tetanus shot? Author(s): Birnbaumer D. Source: Health News. 2002 December; 8(12): 12. No Abstract Available. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12523274&dopt=Abstract

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Randomised study of the possible adjuvant effect of BCG vaccine on the immunogenicity of diphtheria-tetanus-acellular pertussis vaccine in Senegalese infants. Author(s): Simondon F, Preziosi MP, Pinchinat S, Yam A, Chabirand L, Wassilak S, Pines E, Trape JF, Salomon H, Hoffenbach A. Source: European Journal of Clinical Microbiology & Infectious Diseases : Official Publication of the European Society of Clinical Microbiology. 1999 January; 18(1): 23-9. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10192710&dopt=Abstract

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Reactogenicity and immunogenicity at preschool age of a booster dose of two threecomponent diphtheria-tetanus-acellular pertussis vaccines in children primed in infancy with acellular vaccines. Author(s): Tozzi AE, Anemona A, Stefanelli P, Salmaso S, Atti ML, Mastrantonio P, Giammanco A; Progetto Pertosse Study Group. Source: Pediatrics. 2001 February; 107(2): E25. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11158499&dopt=Abstract

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Reactogenicity and immunogenicity of adult versus paediatric diphtheria and tetanus booster dose at 6 years of age. Author(s): Ciofi degli Atti ML, Salmaso S, Cotter B, Gallo G, Alfarone G, Pinto A, Bella A, von Hunolstein C. Source: Vaccine. 2001 October 12; 20(1-2): 74-9. Erratum In: Vaccine 2001 December 12; 20(5-6): 989. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11567748&dopt=Abstract

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Reactogenicity and immunogenicity of reduced antigen content diphtheria-tetanusacellular pertussis vaccines as a booster in 4-7-year-old children primed with diphtheria-tetanus-whole cell pertussis vaccine before 2 years of age. Author(s): Dagan R, Igbaria K, Piglansky L, Van Brusteghem F, Melot V, Kaufhold A. Source: Vaccine. 1999 June 4; 17(20-21): 2620-7. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10418911&dopt=Abstract

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Reactogenicity profile of tetanus-diphtheria (adult-type) vaccine: results of a naturalistic study performed at an adult vaccination center. Author(s): Vilella A, Dal-Re R, Simo D, Garcia-Corbeira P, Diego P, Bayas JM. Source: Journal of Clinical Pharmacology. 2000 November; 40(11): 1267-73. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11075312&dopt=Abstract

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Recently occurring adult tetanus in Korea: emphasis on immunization and awareness of tetanus. Author(s): Shin DH, Yu HS, Park JH, Shin JH, Kim SJ. Source: Journal of Korean Medical Science. 2003 February; 18(1): 11-6. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12589080&dopt=Abstract

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Recombinant and truncated tetanus neurotoxin light chain: cloning, expression, purification, and proteolytic activity. Author(s): Tonello F, Pellizzari R, Pasqualato S, Grandi G, Peggion E, Montecucco C. Source: Protein Expression and Purification. 1999 March; 15(2): 221-7. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10049679&dopt=Abstract

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Recrudescence of cutaneous Mycobacterium haemophilum lesions following tetanus immunization. Author(s): Gibson MK, Villano SA, Huff CA, Cofrancesco J. Source: Clinical Infectious Diseases : an Official Publication of the Infectious Diseases Society of America. 1999 April; 28(4): 919-20. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10825067&dopt=Abstract

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Recurrence of reactive arthritis after a booster dose of tetanus toxoid. Author(s): Kaul A, Adler M, Alokaily F, Jawad AS. Source: Annals of the Rheumatic Diseases. 2002 February; 61(2): 185. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11796415&dopt=Abstract

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Reduced-antigen combined diphtheria-tetanus-acellular pertussis vaccine (Boostrix). Author(s): Chapman TM, Goa KL. Source: Drugs. 2003; 63(13): 1407-13; Discussion: 1415-6. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12825963&dopt=Abstract

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Respiratory failure in tetanus: case report and review of a 25-year experience. Author(s): Bunch TJ, Thalji MK, Pellikka PA, Aksamit TR. Source: Chest. 2002 October; 122(4): 1488-92. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12377887&dopt=Abstract

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Response to immunization with measles, tetanus, and Haemophilus influenzae type b vaccines in children who have human immunodeficiency virus type 1 infection and are treated with highly active antiretroviral therapy. Author(s): Melvin AJ, Mohan KM. Source: Pediatrics. 2003 June; 111(6 Pt 1): E641-4. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12777579&dopt=Abstract

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Retrospective population-based assessment of medically attended injection site reactions, seizures, allergic responses and febrile episodes after acellular pertussis vaccine combined with diphtheria and tetanus toxoids. Author(s): Jackson LA, Carste BA, Malais D, Froeschle J. Source: The Pediatric Infectious Disease Journal. 2002 August; 21(8): 781-6. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12192169&dopt=Abstract

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Risk factors for neonatal tetanus in Ibadan, Nigeria. Author(s): Asekun-Olarinmoye EO, Lawoyin TO, Onadeko MO. Source: European Journal of Pediatrics. 2003 July; 162(7-8): 526-7. Epub 2003 May 16. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12751001&dopt=Abstract

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Safety and immune responses to attenuated Salmonella enterica serovar typhi oral live vector vaccines expressing tetanus toxin fragment C. Author(s): Tacket CO, Galen J, Sztein MB, Losonsky G, Wyant TL, Nataro J, Wasserman SS, Edelman R, Chatfield S, Dougan G, Levine MM. Source: Clinical Immunology (Orlando, Fla.). 2000 November; 97(2): 146-53. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11027455&dopt=Abstract

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Safety and immunogenicity of a combination diphtheria-tetanus toxoids-acellular pertussis-hepatitis B vaccine administered at two, four and six months of age compared with monovalent hepatitis B vaccine administered at birth, one month and six months of age. Author(s): Greenberg DP, Wong VK, Partridge S, Howe BJ, Ward JI. Source: The Pediatric Infectious Disease Journal. 2002 August; 21(8): 769-77. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12192167&dopt=Abstract

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Safety and immunogenicity of a diphtheria, tetanus, and acellular pertussisinactivated poliovirus vaccine/Haemophilus influenzae type B combination vaccine administered to Taiwanese infants at 2, 4, and 6 months of age. Author(s): Lin TY, Wang YH, Chang LY, Chiu CH, Huang YC, Tang H, Bock HL. Source: Chang Gung Med J. 2003 May; 26(5): 315-22. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12934847&dopt=Abstract

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Safety and immunogenicity of a new equine tetanus immunoglobulin associated with tetanus-diphtheria vaccine. Author(s): Lang J, Kamga-Fotso L, Peyrieux JC, Blondeau C, Lutsch C, Forrat R. Source: The American Journal of Tropical Medicine and Hygiene. 2000 NovemberDecember; 63(5-6): 298-305. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11421382&dopt=Abstract

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Safety and immunogenicity of a new Neisseria meningitidis serogroup C-tetanus toxoid conjugate vaccine in healthy adults. Author(s): Richmond P, Goldblatt D, Fusco PC, Fusco JD, Heron I, Clark S, Borrow R, Michon F. Source: Vaccine. 1999 November 12; 18(7-8): 641-6. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10547423&dopt=Abstract

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Safety and immunogenicity of a nonavalent pneumococcal vaccine conjugated to CRM197 administered simultaneously but in a separate syringe with diphtheria, tetanus and pertussis vaccines in Gambian infants. Author(s): Obaro SK, Adegbola RA, Chang I, Banya WA, Jaffar S, Mcadam KW, Greenwood BM. Source: The Pediatric Infectious Disease Journal. 2000 May; 19(5): 463-9. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10819345&dopt=Abstract

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Safety and immunogenicity of a pentavalent diphtheria, tetanus, pertussis, hepatitis B and polio combination vaccine in infants. Author(s): Yeh SH, Ward JI, Partridge S, Marcy SM, Lee H, Jing J, Curry ES, Howe BJ. Source: The Pediatric Infectious Disease Journal. 2001 October; 20(10): 973-80. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11642632&dopt=Abstract

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Safety and immunogenicity of Biken acellular pertussis vaccine in combination with diphtheria and tetanus toxoid as a fifth dose at four to six years of age. Munich Vaccine Study Group. Author(s): Liese JG, Stojanov S, Zink TH, Froeschle J, Klepadlo R, Kronwitter A, Harzer E, Jow S, Belohradsky BH. Source: The Pediatric Infectious Disease Journal. 2001 October; 20(10): 981-8. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11642633&dopt=Abstract

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Safety and immunogenicity of combined diphtheria-tetanus-pertussis (whole cell and acellular)-Haemophilus influenzae-b conjugate vaccines administered to Indonesian children. Author(s): Richie E, Punjabi NH, Harjanto SJ, Wangsasaputral F, Sukandar M, Supriatman M, Simanjuntak CH, Que JU, Cryz SJ Jr. Source: Vaccine. 1999 March 17; 17(11-12): 1384-93. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10195774&dopt=Abstract

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Safety and immunogenicity of combined or associated administration of PRP-T vaccine with diphtheria, tetanus and pertussis vaccine in Thai children. Author(s): Lolekha S, Hiranchote A, Simasathien S. Source: Journal of Tropical Pediatrics. 2001 February; 47(1): 24-9. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11245347&dopt=Abstract

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Safety and immunogenicity of Haemophilus influenzae type b-tetanus toxoid conjugate, presented in a dual-chamber syringe with diphtheria-tetanus-pertussis and inactivated poliomyelitis combination vaccine. Author(s): Langue J, Ethevenaux C, Champsaur A, Fritzell B, Begue P, Saliou P. Source: European Journal of Pediatrics. 1999 September; 158(9): 717-22. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10485302&dopt=Abstract

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Safety and immunogenicity of Haemophilus influenzae-tetanus toxoid conjugate vaccine given separately or in combination with a three-component acellular pertussis vaccine combined with diphtheria and tetanus toxoids and inactivated poliovirus vaccine for the first four doses. Author(s): Halperin SA, King J, Law B, Mills E, Willems P. Source: Clinical Infectious Diseases : an Official Publication of the Infectious Diseases Society of America. 1999 May; 28(5): 995-1001. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10452624&dopt=Abstract

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Safety and immunogenicity of pneumococcal conjugate vaccine in combination with diphtheria, tetanus toxoid, pertussis and Haemophilus influenzae type b conjugate vaccine. Author(s): Obaro SK, Enwere GC, Deloria M, Jaffar S, Goldblatt D, Brainsby K, Hallander H, McInnes P, Greenwood BM, McAdam KP. Source: The Pediatric Infectious Disease Journal. 2002 October; 21(10): 940-7. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12394817&dopt=Abstract

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Safety and immunogenicity of two Haemophilus influenzae type b polysaccharidetetanus toxoid conjugate vaccines (PRP-T) given with diphtheria-tetanus-pertussis vaccine to young Papua New Guinean children. Author(s): Lehmann D, Kakazo M, Saleu G, Taime J, Javati A, Namuigi P, Alpers MP, Wegmuller B, Zellmeyer M, Furer E, Que JU, Herzog C. Source: P N G Med J. 2001 March-June; 44(1-2): 6-16. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12418673&dopt=Abstract

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Salivary anti-capsular antibodies in infants and children immunised with Streptococcus pneumoniae capsular polysaccharides conjugated to diphtheria or tetanus toxoid. Author(s): Korkeila M, Lehtonen H, Ahman H, Leroy O, Eskola J, Kayhty H. Source: Vaccine. 2000 January 18; 18(13): 1218-26. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10649623&dopt=Abstract

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Semi-permanent cardiac pacing in severe tetanus. Author(s): Millo JL, Culshaw MC, Alp NJ, Salmon JB. Source: British Journal of Anaesthesia. 2002 June; 88(6): 882. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12173219&dopt=Abstract

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Sentinel surveillance on poliomyelitis and neonatal tetanus: a report. Author(s): Ray SK, Saha I, Dasgupta S. Source: Indian J Public Health. 1998 October-December; 42(4): 120-5. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10389524&dopt=Abstract

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Sero-epidemiology of tetanus antibody among the children in eastern Turkey. Author(s): Inandi T, Ertekin V, Ayyildiz A. Source: Public Health. 2002 November; 116(6): 379-82. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12407479&dopt=Abstract

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Serologic immunity to diphtheria and tetanus in the United States. Author(s): Ann Intern Med. 2002 May 7;136(9):660-6 Source: Annals of Internal Medicine. 2002 May 7; 136(9): 660-6. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11992301

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Serological assays as alternatives to the Ph Eur challenge test for batch release of tetanus vaccines for human use. Author(s): Winsnes R, Hendriksen C, Sesardic D, Akkermans A, Daas A. Source: Dev Biol Stand. 1999; 101: 277-88. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10566802&dopt=Abstract

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Serological methods for potency testing of tetanus toxoid vaccines for human use. Author(s): Hendriksen C, Winsnes R. Source: Dev Biol (Basel). 2002; 111: 131-40. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12678232&dopt=Abstract

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Serological response to immunization with tetanus toxoid. Author(s): Setarunnahar, Hossain A, Khatun R, Parveen S, Ahmad Z, Haleem A, Alam SK. Source: Bangladesh Med Res Counc Bull. 2000 April; 26(1): 15-22. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11192490&dopt=Abstract

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Seroprevalence of tetanus antibody in Turkish population and effectiveness of single-dose tetanus toxoid. Author(s): Cavuslu S, Oncul O, Altunay H, Ozsoy MF, Kocak N. Source: European Journal of Clinical Microbiology & Infectious Diseases : Official Publication of the European Society of Clinical Microbiology. 2003 July; 22(7): 431-3. Epub 2003 June 26. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12884073&dopt=Abstract

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Severe anuric renal failure in a patient with tetanus. Author(s): Asherson AP, Ruttmann TG. Source: British Journal of Anaesthesia. 2002 May; 88(5): 740-1; Author Reply 741-2. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12067022&dopt=Abstract

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Should tetanus toxoid be administered every 5 years. Author(s): Paul Y. Source: Indian Pediatrics. 2000 July; 37(7): 795-6. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10906819&dopt=Abstract

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Simultaneous administration of meningococcal C conjugate vaccine and diphtheriatetanus-acellular pertussis-inactivated poliovirus-Haemophilus influenzae type b conjugate vaccine in children: a randomized double-blind study. Author(s): Halperin SA, McDonald J, Samson L, Danzig L, Santos G, Izu A, Smith B, MacDonald N. Source: Clinical and Investigative Medicine. Medecine Clinique Et Experimentale. 2002 December; 25(6): 243-51. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12516995&dopt=Abstract

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Specific IgA subclass responses in serum and saliva: a 12-month follow-up study after parenteral booster immunization with tetanus toxoid. Author(s): Engstrom PE, Gustafson R, Granberg M, Engstrom GN. Source: Acta Odontologica Scandinavica. 2002 August; 60(4): 198-202. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12222642&dopt=Abstract

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Standard and alternative regimens of Haemophilus influenzae type b conjugate vaccine (polyribosylribitol phosphate-tetanus toxoid conjugate vaccine) elicit comparable antibody avidities in infants. Author(s): Campbell JD, Lagos R, Levine MM, Losonsky GA. Source: The Pediatric Infectious Disease Journal. 2002 September; 21(9): 822-6. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12352802&dopt=Abstract

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Studies on a Hib-tetanus toxoid conjugate vaccine: effects of co-administered tetanus toxoid vaccine, of administration route and of combined administration with an inactivated polio vaccine. Author(s): Carlsson RM, Claesson BA, Kayhty H, Selstam U, Iwarson S. Source: Vaccine. 1999 October 14; 18(5-6): 468-78. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10519936&dopt=Abstract

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Susceptibility to tetanus and missed vaccination opportunities in Portuguese women. Author(s): Goncalves G, Santos MA, Cutts FT, Barros H. Source: Vaccine. 1999 April 9; 17(15-16): 1820-5. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10217579&dopt=Abstract

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Tetanus after white-lipped green pit viper (Trimeresurus albolabris) bite. Author(s): Suankratay C, Wilde H, Nunthapisud P, Khantipong M. Source: Wilderness Environ Med. 2002 Winter; 13(4): 256-61. No Abstract Available. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12510783&dopt=Abstract

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Tetanus and diphtheria toxoids now available. Author(s): Furste W. Source: The Journal of Trauma. 2002 December; 53(6): 1192. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12478053&dopt=Abstract

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Tetanus antitoxin levels among adults over 40 years of age in Central Anatolia, Turkey. Author(s): Ozturk A, Goahmetoglu S, Erdem F, Mysguroglu Alkan S. Source: Clinical Microbiology and Infection : the Official Publication of the European Society of Clinical Microbiology and Infectious Diseases. 2003 January; 9(1): 33-8. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12691540&dopt=Abstract

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Tetanus antitoxin seroprevalence in patients with Behcet's disease. Author(s): Ayaslioglu E, Erkek E, Kilic D, Kaygusuz S, Karaca F, Duzgun N. Source: Scandinavian Journal of Infectious Diseases. 2003; 35(5): 299-301. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12875513&dopt=Abstract

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Tetanus complicating snakebite in northern Nigeria: clinical presentation and public health implications. Author(s): Habib AG. Source: Acta Tropica. 2003 January; 85(1): 87-91. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12505187&dopt=Abstract

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Tetanus immunisation in geriatric patients with accidental wounds: how much is needed? Author(s): Hullstrung HD, Mausezahl D, Feuz M, Herzog C, Conzelmann M, Zimmerli W. Source: Swiss Medical Weekly : Official Journal of the Swiss Society of Infectious Diseases, the Swiss Society of Internal Medicine, the Swiss Society of Pneumology. 2003 April 19; 133(15-16): 227-32. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12811672&dopt=Abstract

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Tetanus immunisation in hypersensitive individuals. Author(s): Williams AN, Kabuubi JB, Owen JP, Wells J. Source: J R Army Med Corps. 2002 June; 148(2): 148-50. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12174558&dopt=Abstract

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Tetanus immunity among pregnant women attending antenatal care in Dar es Salaam, Tanzania. Author(s): Aboud S, Lyamuya EF, Kristoffersen EK, Matre R. Source: Afr J Reprod Health. 2002 August; 6(2): 87-93. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12476720&dopt=Abstract

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Tetanus immunity in long-term care facilities. Author(s): Fernandes R, Valcour V, Flynn B, Masaki K, Blanchette P. Source: Journal of the American Geriatrics Society. 2003 August; 51(8): 1116-9. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12890075&dopt=Abstract

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Tetanus immunization in pregnant women. Serum levels of antitetanus antibodies at time of delivery. Author(s): Maral I, Cirak M, Aksakal FN, Baykan Z, Kayikcioglu F, Bumin MA. Source: European Journal of Epidemiology. 2001; 17(7): 661-5. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12086080&dopt=Abstract

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Tetanus immunization shortage in the United States. Author(s): Zun LS, Downey L. Source: The American Journal of Emergency Medicine. 2003 July; 21(4): 298-301. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12898486&dopt=Abstract

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Tetanus in a renal transplant recipient exhibiting the presence of circulating antitetanus antibodies determined by ELISA. Author(s): de La Chapelle A, Lavabre O, Pinsard M, Delamonica J, Relyveld EH. Source: Biomedicine & Pharmacotherapy = Biomedecine & Pharmacotherapie. 2002 June; 56(4): 208-10. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12109814&dopt=Abstract

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Tetanus in developing countries: an update on the Maternal and Neonatal Tetanus Elimination Initiative. Author(s): Vandelaer J, Birmingham M, Gasse F, Kurian M, Shaw C, Garnier S. Source: Vaccine. 2003 July 28; 21(24): 3442-5. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12850356&dopt=Abstract

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Tetanus in England and Wales, 1984-2000. Author(s): Rushdy AA, White JM, Ramsay ME, Crowcroft NS. Source: Epidemiology and Infection. 2003 February; 130(1): 71-7. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12613747&dopt=Abstract

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Tetanus infection from a superinfected cranial squamous cell carcinoma. Author(s): Landes CA, Seeger F, Kovacs AF. Source: Plastic and Reconstructive Surgery. 2003 October; 112(5): 1347-9. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=14504518&dopt=Abstract

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Tetanus prophylaxis in the A&E department. Author(s): Adeboye KA, Sangowawa O. Source: Journal of the Royal Society of Medicine. 2002 March; 95(3): 113. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11872757&dopt=Abstract

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Tetanus seroprevalence among farmers: a preliminary study. Author(s): Hayney MS, Love GD, Carlberg BM, Buck JM, Muller D. Source: The Journal of Rural Health : Official Journal of the American Rural Health Association and the National Rural Health Care Association. 2003 Spring; 19(2): 109-12. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12696846&dopt=Abstract

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Tetanus surveillance--United States, 1991-1994. Author(s): Izurieta HS, Sutter RW, Strebel PM, Bardenheier B, Prevots DR, Wharton M, Hadler SC. Source: Mmwr. Cdc Surveillance Summaries : Morbidity and Mortality Weekly Report. Cdc Surveillance Summaries / Centers for Disease Control. 1997 February 21; 46(2): 1525. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12412769&dopt=Abstract

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Tetanus surveillance--United States, 1998--2000. Author(s): Pascual FB, McGinley EL, Zanardi LR, Cortese MM, Murphy TV. Source: Mmwr. Surveillance Summaries : Morbidity and Mortality Weekly Report. Surveillance Summaries / Cdc. 2003 June 20; 52(3): 1-8. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12825541&dopt=Abstract

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Tetanus toxin abolishes exocytosis of ROMK1 induced by inhibition of protein tyrosine kinase. Author(s): Sterling H, Lin DH, Wei Y, Wang WH. Source: American Journal of Physiology. Renal Physiology. 2003 March; 284(3): F510-7. Epub 2002 December 30. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12556363&dopt=Abstract

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Tetanus toxin fragment C-specific priming by intranasal infection with recombinant Bordetella pertussis. Author(s): Reveneau N, Alonso S, Jacob-Dubuisson F, Mercenier A, Locht C. Source: Vaccine. 2001 December 12; 20(5-6): 926-33. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11738759&dopt=Abstract

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Tetanus toxoid coverage as an indicator of serological protection against neonatal tetanus. Author(s): Deming MS, Roungou JB, Kristiansen M, Heron I, Yango A, Guenengafo A, Ndamobissi R. Source: Bulletin of the World Health Organization. 2002; 80(9): 696-703. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12378286&dopt=Abstract

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Tetanus. Author(s): Bhatia R, Prabhakar S, Grover VK. Source: Neurology India. 2002 December; 50(4): 398-407. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12577086&dopt=Abstract

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Tetanus: a case report, epidemiology review and recommendations for immunization compliance. Author(s): Cannarella R, Agbayani E. Source: W V Med J. 2001 September-October; 97(5): 253-6. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11761652&dopt=Abstract

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Tetanus: continuing problem in the developing world. Author(s): Oladiran I, Meier DE, Ojelade AA, OlaOlorun DA, Adeniran A, Tarpley JL. Source: World Journal of Surgery. 2002 October; 26(10): 1282-5. Epub 2002 September 06. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12209228&dopt=Abstract

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The altered whistle in tetanus. Author(s): Dunn ER. Source: The Medical Journal of Australia. 2002 December 2-16; 177(11-12): 687. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12464005&dopt=Abstract

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The genome sequence of Clostridium tetani, the causative agent of tetanus disease. Author(s): Bruggemann H, Baumer S, Fricke WF, Wiezer A, Liesegang H, Decker I, Herzberg C, Martinez-Arias R, Merkl R, Henne A, Gottschalk G. Source: Proceedings of the National Academy of Sciences of the United States of America. 2003 February 4; 100(3): 1316-21. Epub 2003 January 27. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12552129&dopt=Abstract

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The journey of tetanus and botulinum neurotoxins in neurons. Author(s): Lalli G, Bohnert S, Deinhardt K, Verastegui C, Schiavo G. Source: Trends in Microbiology. 2003 September; 11(9): 431-7. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=13678859&dopt=Abstract

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Transfusion support with RBCs from an Mk homozygote in a case of autoimmune hemolytic anemia following diphtheria-pertussis-tetanus vaccination. Author(s): Johnson ST, McFarland JG, Kelly KJ, Casper JT, Gottschall JL. Source: Transfusion. 2002 May; 42(5): 567-71. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12084164&dopt=Abstract

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Transient cross-resistance to neuromuscular blocking agents in a patient with tetanus. Author(s): Chiu JW, Tsou CH, Liou JT, Hsin ST, Luk HN. Source: Anesthesiology. 2003 February; 98(2): 579-81. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12552222&dopt=Abstract

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Universal epitopes for human CD4+ cells on tetanus and diphtheria toxins. Author(s): Diethelm-Okita BM, Okita DK, Banaszak L, Conti-Fine BM. Source: The Journal of Infectious Diseases. 2000 March; 181(3): 1001-9. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10720523&dopt=Abstract

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Use of capsular polysaccharide-tetanus toxoid conjugate vaccine for type II group B Streptococcus in healthy women. Author(s): Baker CJ, Paoletti LC, Rench MA, Guttormsen HK, Carey VJ, Hickman ME, Kasper DL. Source: The Journal of Infectious Diseases. 2000 October; 182(4): 1129-38. Epub 2000 September 08. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10979909&dopt=Abstract

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Use of lidocaine-prilocaine patch to decrease intramuscular injection pain does not adversely affect the antibody response to diphtheria-tetanus-acellular pertussisinactivated poliovirus-Haemophilus influenzae type b conjugate and hepatitis B vaccines in infants from birth to six months of age. Author(s): Halperin BA, Halperin SA, McGrath P, Smith B, Houston T. Source: The Pediatric Infectious Disease Journal. 2002 May; 21(5): 399-405. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12150176&dopt=Abstract

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Use of magnesium to treat tetanus. Author(s): Williams S. Source: British Journal of Anaesthesia. 2002 January; 88(1): 152-3; Author Reply 153. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11881879&dopt=Abstract

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Vaccination of COPD patients with a pneumococcus type 6B tetanus toxoid conjugate vaccine. Author(s): Jonsson S, Vidarsson G, Valdimarsson H, Schiffman G, Schneerson R, Jonsdottir I. Source: The European Respiratory Journal : Official Journal of the European Society for Clinical Respiratory Physiology. 2002 October; 20(4): 813-8. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12412669&dopt=Abstract

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Validity of neck stiffness as a predictor for death from tetanus. Author(s): Nishioka SA. Source: Revista Do Instituto De Medicina Tropical De Sao Paulo. 2001 March-April; 43(2): 117-8. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11340488&dopt=Abstract

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CHAPTER 2. NUTRITION AND TETANUS Overview In this chapter, we will show you how to find studies dedicated specifically to nutrition and tetanus.

Finding Nutrition Studies on Tetanus 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 “tetanus” (or synonyms) into the search box, and click “Go.” To narrow the search, you can also select the “Title” field.

7 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 information is typical of that found when using the “Full IBIDS Database” to search for “tetanus” (or a synonym): •

“Sucrose analgesia” and diphtheria-tetanus-pertussis immunizations at 2 and 4 months. Author(s): Department of Pediatrics, McGill University, Montreal, Canada. Source: Barr, R G Young, S N Wright, J H Cassidy, K L Hendricks, L Bedard, Y Yaremko, J Leduc, D Treherne, S J-Dev-Behav-Pediatr. 1995 August; 16(4): 220-5 0196-206X

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A multiaxial constitutive law for mammalian left ventricular myocardium in steadystate barium contracture or tetanus. Author(s): Department of Biomedical Engineering, Johns Hopkins University School of Medicine, Baltimore, MD 21287, USA. Source: Lin, D H Yin, F C J-Biomech-Eng. 1998 August; 120(4): 504-17 0148-0731

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A reassessment of risk factors for neonatal tetanus. Author(s): Child Survival Project, Global 2000, Inc., Carter Center, Islamabad, Pakistan. Source: Traverso, H P Kamil, S Rahim, H Samadi, A R Boring, J R Bennett, J V BullWorld-Health-Organ. 1991; 69(5): 573-9 0042-9686

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Activation of signal transduction pathways involving trkA, PLCgamma-1, PKC isoforms and ERK-1/2 by tetanus toxin. Author(s): Departament de Bioquimica i de Biologia Molecular, Facultat de Medicina, Universitat Autonoma de Barcelona, E-08193 (Barcelona), Catalunya, Bellaterra, Spain. Source: Gil, C Chaib Oukadour, I Pelliccioni, P Aguilera, J FEBS-Lett. 2000 September 15; 481(2): 177-82 0014-5793

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Acute radiculomyelitis after antitetanus vaccination. Author(s): Divisione di Neurologia, Ospedale Civile Maggiore, Verona. Source: Tezzon, F Tomelleri, P Ferrari, G Sergi, A Ital-J-Neurol-Sci. 1994 May; 15(4): 1913 0392-0461

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Affinity purified tetanus toxin binds to isolated chromaffin granules and inhibits catecholamine release in digitonin-permeabilized chromaffin cells. Author(s): Department of Pharmacology and Experimental Therapeutics, Hadassah School of Medicine, Jerusalem, Israel. Source: Lazarovici, P Fujita, K Contreras, M L DiOrio, J P Lelkes, P I FEBS-Lett. 1989 August 14; 253(1-2): 121-8 0014-5793

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ATP release from pure cholinergic synaptosomes is not blocked by tetanus toxin. Source: Rabasseda, X Solsona, C Marsal, J Egea, G Bizzini, B FEBS-Lett. 1987 Mar 23; 213(2): 337-40 0014-5793

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Biochemical analyses of the inhibition of catecholamine release by tetanus toxin in digitonin-permeabilized chromaffin cells. Author(s): Department of Tuberculosis Research I, Osaka University. Source: Okabe, T Sugimoto, N Matsuda, M Jpn-J-Med-Sci-Biol. 1990 December; 43(6): 266-7 0021-5112

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Black tea extract, thearubigin fraction, counteracts the effect of tetanus toxin in mice. Author(s): Department of Pharmacology, University of Obihiro School of Veterinary Medicine, Obihiro 080-8555, Japan. Source: Satoh, E Ishii, T Shimizu, Y Sawamura, S Nishimura, M Exp-Biol-Med(Maywood). 2001 June; 226(6): 577-80

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Further observations on ghee as a risk factor for neonatal tetanus. Author(s): Task Force for Child Survival and Development, Carter Center, Atlanta, GA 30307, USA.

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Source: Bennett, J Azhar, N Rahim, F Kamil, S Traverso, H Killgore, G Boring, J Int-JEpidemiol. 1995 June; 24(3): 643-7 0300-5771 •

In vitro immunization for antibody production against tetanus toxin and toxoid. 3. Recombinant gamma interferon and indomethacin support specific antibody production induced by antigen-pulsed immobilized monocytes. Author(s): Department of Medicine Charite, Humboldt-University, Berlin. Source: Jahn, S Grunow, R Kiesing, S T Volk, H D von Baehr, R Allerg-Immunol-(Leipz). 1987; 33(4): 239-44 0323-4398

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Mechanism of action of tetanus and botulinum neurotoxins. Source: Montecucco, C. Schiavo, G. Mol-microbiol. Oxford : Blackwell Scientific Publications,. July 1994. volume 13 (1) page 1-8. 0950-382X

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Neonatal tetanus associated with topical umbilical ghee: covert role of cow dung. Author(s): Department of Epidemiology, Rollins School of Public Health, Atlanta, Georgia 30322, USA. Source: Bennett, J Ma, C Traverso, H Agha, S B Boring, J Int-J-Epidemiol. 1999 December; 28(6): 1172-5 0300-5771

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Oxygen or glucose deprivation-induced neuronal injury in cortical cell cultures is reduced by tetanus toxin. Author(s): Department of Neurology and Neurological Sciences, Stanford University Medical Center, California 94305. Source: Monyer, H Giffard, R G Hartley, D M Dugan, L L Goldberg, M P Choi, D W Neuron. 1992 May; 8(5): 967-73 0896-6273

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Pyridoxine in the treatment of tetanus neonatorum. Author(s): Dr. Sami Ulus Children's Hospital, Ankara, Turkey. Source: Caglar, M K Paediatr-Indones. 1989 Nov-December; 29(11-12): 233-6 0030-9311

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Quantitation of anti-tetanus and anti-diphtheria antibodies by enzymoimmunoassay: methodology and applications. Author(s): Department of Microbiology and Immunology, Medical University of South Carolina, Charleston 29425. Source: Virella, G Hyman, B J-Clin-Lab-Anal. 1991; 5(1): 43-8 0887-8013

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Role of aluminium in skin reactions after diphtheria-tetanus-pertussis-poliomyelitis vaccination: an experimental study in rabbits. Author(s): Laboratoire de Toxicologie et d'Hygiene Industrielle, Faculte de Pharmacie, Centre Hospitalier Regional Universitaire, Nantes, France. Source: Pineau, A Durand, C Guillard, O Bureau, B Stalder, J F Toxicology. 1992; 73(1): 117-25 0300-483X

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Role of transglutaminase in [3H]5-HT release from synaptosomes and in the inhibitory effect of tetanus toxin. Author(s): Istituto di Ricerche Farmacologiche, Mario Negri, Milano, Italy. Source: Gobbi, M Frittoli, E Mennini, T Neurochem-Int. 1996 August; 29(2): 129-34 01970186

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Serotonin transporter phosphorylation modulated by tetanus toxin. Author(s): Departament de Bioquimica i de Biologia Molecular, Facultat de Medicina, Universitat Autonoma de Barcelona, E-08193 Cerdanyola del Valles, Barcelona, Spain. Source: Najib, A Pelliccioni, P Gil, C Aguilera, J FEBS-Lett. 2000 December 8; 486(2): 13642 0014-5793

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Stimulating role of toxoids-laden liposomes in oral immunization against diphtheria and tetanus infections. Author(s): Razi State Serum and Vaccine Institute, Tehran, Islamic Republic of Iran. Source: Mirchamsy, H Manhouri, H Hamedi, M Ahourai, P Fateh, G Hamzeloo, Z Biologicals. 1996 December; 24(4): 343-50 1045-1056

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Tetanus after induced abortion--a case report. Author(s): Department of Anaesthesiology, Faculty of Medicine, Universiti Kebangsaan Malaysia, Kuala Lumpur. Source: bin Misiran, K Med-J-Malaysia. 1990 December; 45(4): 349-52 0300-5283

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Tetanus toxin is a zinc protein and its inhibition of neurotransmitter release and protease activity depend on zinc. Author(s): Centro CNR Biomembrane, Universita di Padova, Italy. Source: Schiavo, G Poulain, B Rossetto, O Benfenati, F Tauc, L Montecucco, C EMBO-J. 1992 October; 11(10): 3577-83 0261-4189

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Tetanus toxin-induced protein kinase C activation and elevated serotonin levels in the perinatal rat brain. Author(s): Department of Neurobiology, Weizmann Institute of Science, Rehovot, Israel. Source: Aguilera, J Lopez, L A Yavin, E FEBS-Lett. 1990 April 9; 263(1): 61-5 0014-5793

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The effect of different quantities and compositions of pelleted diets on immune response of mares during the production of anti-tetanus sera. Author(s): Faculty of Agriculture, University of Zagreb, 10000 Zagreb, Svetosimunska c. 25, Croatia. Source: Rupic, V Bacar Huskic, L Lojkic, M Habe, F Ergotic, N Berl-Munch-TierarztlWochenschr. 2001 May-June; 114(5-6): 188-92 0005-9366

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The effect of lanthanum on nerve terminals in goldfish muscle after paralysis with tetanus toxin. Author(s): Department of Experimental Psychology, University of Oxford, U.K. Source: Mellanby, J Beaumont, M A Thompson, P A Neuroscience. 1988 June; 25(3): 1095-106 0306-4522

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The influence of pyridoxin in the treatment of tetanus neonatorum. Author(s): Department of Child Health, Gunung Wenang Hospital Medical School, Sam Ratulangi University, Manado. Source: Dianto Mustadjab, I Paediatr-Indones. 1991 May-June; 31(5-6): 165-9 0030-9311

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The inhibition by pertussis and tetanus toxins of evoked catecholamine release from intact and permeabilized bovine adrenal chromaffin cells. Author(s): Department of Biochemistry, University of Edinburgh, UK. Source: Bansal, M K Phillips, J H van Heyningen, S FEBS-Lett. 1990 December 10; 276(12): 165-8 0014-5793

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The tetanus toxin light chain inhibits exocytosis. Author(s): Abteilung Anatomie und Zellbiologie, Universitat Ulm, FRG. Source: Ahnert Hilger, G Weller, U Dauzenroth, M E Habermann, E Gratzl, M FEBSLett. 1989 January 2; 242(2): 245-8 0014-5793

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The use of continuous atropine infusion in the management of severe tetanus. Author(s): Cerrahpasa Medical Faculty, Department of Anesthesiology, Istanbul University, Turkey. Source: Dolar, D Intensive-Care-Med. 1992; 18(1): 26-31 0342-4642

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Uvulectomy as an epidemiological factor in neonatal tetanus mortality:- observations from a cluster survey. Author(s): Department of Paediatrics, Specialist Hospital, Yola, Adamawa State, Nigeria. Source: Eregie, C O West-Afr-J-Med. 1994 Jan-March; 13(1): 56-8 0189-160X

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Zinc supplementation stimulates tetanus antibody formation and soluble interleukin2 receptor levels in chronic hemodialysis patients. Author(s): Medizinische Klinik, Krankenhaus Maria Hilf GmbH Monchengladbach, Akademisches Lehrkrankenhaus, RWTH Aachen. Source: Holtkamp, W Brodersen, H P Stollberg, T Thiery, J Falkner, C Clin-Investig. 1993 July; 71(7): 537-41 0941-0198

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

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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

The following is a specific Web list relating to tetanus; 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: •

Vitamins Vitamin E Source: Prima Communications, Inc.www.personalhealthzone.com

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CHAPTER 3. ALTERNATIVE MEDICINE AND TETANUS Overview In this chapter, we will begin by introducing you to official information sources on complementary and alternative medicine (CAM) relating to tetanus. 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 tetanus 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 “tetanus” (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 tetanus: •

A mechanism of the thearubigin fraction of black tea (Camellia sinensis) extract protecting against the effect of tetanus toxin. Author(s): Satoh E, Ishii T, Shimizu Y, Sawamura S, Nishimura M. Source: J Toxicol Sci. 2002 December; 27(5): 441-7. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12533914&dopt=Abstract

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A reassessment of risk factors for neonatal tetanus. Author(s): Traverso HP, Kamil S, Rahim H, Samadi AR, Boring JR, Bennett JV. Source: Bulletin of the World Health Organization. 1991; 69(5): 573-9. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=1959158&dopt=Abstract

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Acupuncture used as an adjunct in the treatment of a horse with tetanus. Author(s): White SS, Christie MP.

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Source: Aust Vet J. 1985 January; 62(1): 25-6. No Abstract Available. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=4004654&dopt=Abstract •

Adequate immune response to tetanus toxoid and failure of vitamin A and E supplementation to enhance antibody response in healthy children. Author(s): Kutukculer N, Akil T, Egemen A, Kurugol Z, Aksit S, Ozmen D, Turgan N, Bayindir O, Caglayan S. Source: Vaccine. 2000 July 1; 18(26): 2979-84. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10825599&dopt=Abstract

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Autonomic complications in a case of severe tetanus. Author(s): Kerr JH, Travis KW, O'Rourke RA, Sims JK, Uhl RR. Source: The American Journal of Medicine. 1974 August; 57(2): 303-10. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=4602198&dopt=Abstract

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Black tea extract, thearubigin fraction, counteracts the effect of tetanus toxin in mice. Author(s): Satoh E, Ishii T, Shimizu Y, Sawamura S, Nishimura M. Source: Experimental Biology and Medicine (Maywood, N.J.). 2001 June; 226(6): 577-80. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11395929&dopt=Abstract

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Caffeine treatment inhibits drug-induced calcium release from sarcoplasmic reticulum and caffeine contracture but not tetanus in frog skeletal muscle. Author(s): Koshita M, Oba T. Source: Canadian Journal of Physiology and Pharmacology. 1989 August; 67(8): 890-5. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=2557143&dopt=Abstract

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Cardiovascular disturbances in severe tetanus due to overactivity of the sympathetic nervous system. Author(s): Corbett JL, Kerr JH, Prys-Roberts C, Smith AC, Spalding JM. Source: Anaesthesia. 1969 April; 24(2): 198-212. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=5774711&dopt=Abstract

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Characterization of the binding and internalization of tetanus toxin in a neuroblastoma hybrid cell line. Author(s): Staub GC, Walton KM, Schnaar RL, Nichols T, Baichwal R, Sandberg K, Rogers TB. Source: The Journal of Neuroscience : the Official Journal of the Society for Neuroscience. 1986 May; 6(5): 1443-51. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=3711989&dopt=Abstract

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Chromium supplementation enhances antibody response to vaccination with tetanus toxoid in cattle. Author(s): Faldyna M, Pechova A, Krejci J.

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Source: Journal of Veterinary Medicine. B, Infectious Diseases and Veterinary Public Health. 2003 September; 50(7): 326-31. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=14535930&dopt=Abstract •

Comparison of adjuvant activities of aluminium phosphate, calcium phosphate and stearyl tyrosine for tetanus toxoid. Author(s): Gupta RK, Siber GR. Source: Biologicals : Journal of the International Association of Biological Standardization. 1994 March; 22(1): 53-63. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=8068314&dopt=Abstract

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Control of tetanus neonatorum in rural communities--immunization effects of highdose calcium phosphate-absorbed tetanus toxoid. Author(s): Kielmann AA, Vohra SR. Source: The Indian Journal of Medical Research. 1977 December; 66(6): 906-16. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=346478&dopt=Abstract

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Cow dung, rock salt, and medical innovation in the Hindu Kush of Pakistan: the cultural transformation of neonatal tetanus and iodine deficiency. Author(s): Mull DS, Anderson JW, Mull JD. Source: Social Science & Medicine (1982). 1990; 30(6): 675-91. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=2315737&dopt=Abstract

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Cross cultural communication of tetanus vaccinations in Bolivia. Author(s): Bastien JW. Source: Social Science & Medicine (1982). 1995 July; 41(1): 77-86. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=7667675&dopt=Abstract

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Development of an operational synaptobrevin-based fluorescent substrate for tetanus neurotoxin quantification. Author(s): Perpetuo EA, Juliano L, Prado SM, Fratelli F, Fernandes I, Lebrun I. Source: Biotechnology and Applied Biochemistry. 2002 December; 36(Pt 3): 155-61. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12452798&dopt=Abstract

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Effect of hyperbaric oxygenation on neonatal tetanus. Author(s): Rhea JW, Graham AW Jr, Akhnoukh F, Parthew CT. Source: The Journal of Pediatrics. 1967 July; 71(1): 33-8. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=5293856&dopt=Abstract

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Effect of vitamin A supplementation on immunoglobulin G subclass responses to tetanus toxoid in children. Author(s): Semba RD, Muhilal, Scott AL, Natadisastra G, West KP Jr, Sommer A.

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Source: Clinical and Diagnostic Laboratory Immunology. 1994 March; 1(2): 172-5. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=7496940&dopt=Abstract •

Effects of diphtheria-tetanus-pertussis or tetanus vaccination on allergies and allergyrelated respiratory symptoms among children and adolescents in the United States. Author(s): Hurwitz EL, Morgenstern H. Source: Journal of Manipulative and Physiological Therapeutics. 2000 February; 23(2): 81-90. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10714532&dopt=Abstract

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Epidemiological factors associated with neonatal tetanus mortality: observations from a cluster survey in Nigeria. Author(s): Eregie CO. Source: East Afr Med J. 1993 July; 70(7): 434-7. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=8293702&dopt=Abstract

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Evidence for a link between specific proteolysis and inhibition of [3H]-noradrenaline release by the light chain of tetanus toxin. Author(s): Sanders D, Habermann E. Source: Naunyn-Schmiedeberg's Archives of Pharmacology. 1992 September; 346(3): 358-61. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=1407019&dopt=Abstract

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Exposure to hyperbaric oxygen not beneficial for murine tetanus. Author(s): Hill GB, Osterhout S. Source: The Journal of Infectious Diseases. 1973 August; 128(2): 238-42. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=4723086&dopt=Abstract

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Factors associated with neonatal tetanus mortality in northern Nigeria. Author(s): Eregie CO, Ofovwe G. Source: East Afr Med J. 1995 August; 72(8): 507-9. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=7588145&dopt=Abstract

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Failure of a large dose of vitamin A to enhance the antibody response to tetanus toxoid in children. Author(s): Brown KH, Rajan MM, Chakraborty J, Aziz KM. Source: The American Journal of Clinical Nutrition. 1980 February; 33(2): 212-7. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=7355795&dopt=Abstract

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Fatal maternal tetanus following premature rupture of membranes and retained dead fetus. Author(s): Okonofua FE, Esen UI, Bamgbose JK.


Source: Trop Geogr Med. 1990 April; 42(2): 166-7. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=2260216&dopt=Abstract •

Further observations on ghee as a risk factor for neonatal tetanus. Author(s): Bennett J, Azhar N, Rahim F, Kamil S, Traverso H, Killgore G, Boring J. Source: International Journal of Epidemiology. 1995 June; 24(3): 643-7. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=7672909&dopt=Abstract

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Ghee applications to the umbilical cord: a risk factor for neonatal tetanus. Author(s): Traverso HP, Bennett JV, Kahn AJ, Agha SB, Rahim H, Kamil S, Lang MH. Source: Lancet. 1989 March 4; 1(8636): 486-8. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=2563851&dopt=Abstract

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Hyperbaric oxygen therapy and tetanus; two cases. Author(s): Porter H Jr, Decker JS, Jenkins MQ. Source: J S C Med Assoc. 1965 November; 61(11): 343-9. No Abstract Available. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=5214181&dopt=Abstract

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Hyperbaric oxygen therapy in mice injected with tetanus toxin. Author(s): Christensen NA, Ackerman E, Weed LA, Gatewood LC, Drube C. Source: Jama : the Journal of the American Medical Association. 1967 April 10; 200(2): 129-31. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=6071380&dopt=Abstract

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Hyperbaric oxygen therapy in tetanus. Author(s): Milledge JS. Source: Jama : the Journal of the American Medical Association. 1968 March 4; 203(10): 875-6. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=4865771&dopt=Abstract

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Hyperbaric oxygen treatment following injection of tetanus toxin in mice. Author(s): Ro J. Source: Acta Pathol Microbiol Scand. 1965; 65(3): 421-5. No Abstract Available. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=5884702&dopt=Abstract

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Hyperbaric treatment of experimental tetanus in Swiss mice. Author(s): Lockwood WR, Langston LL Jr. Source: Curr Ther Res Clin Exp. 1970 May; 12(5): 311-6. No Abstract Available. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=4986246&dopt=Abstract

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Immunologic memory is established in nursling rats immunized with tetanus toxoid, but is not affected by concurrent supplementation with vitamin A. Author(s): Gardner EM, Ross AC. Source: The American Journal of Clinical Nutrition. 1995 November; 62(5): 1007-12. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=7572724&dopt=Abstract

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Impact of universal immunization programme on the incidence of tetanus neonatorum. Author(s): Joshi PL, Bhattacharya M, Arya RC, Raj B, Walia D. Source: Indian Pediatrics. 1992 June; 29(6): 773-5. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=1500143&dopt=Abstract

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Impaired response of lymphocytes from non-insulin-dependent diabetics to staphage lysate and tetanus antigen. Author(s): Casey J, Sturm C Jr. Source: Journal of Clinical Microbiology. 1982 January; 15(1): 109-14. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=7186900&dopt=Abstract

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Inactivation of botulinum and tetanus toxins by chelators. Author(s): Bhattacharyya SD, Sugiyama H. Source: Infection and Immunity. 1989 October; 57(10): 3053-7. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=2506129&dopt=Abstract

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Intraaxonal and extraaxonal transport of 125I-tetanus toxin in early local tetanus. Author(s): Erdmann G, Wiegand H, Wellhoner HH. Source: Naunyn-Schmiedeberg's Archives of Pharmacology. 1975 October 15; 290(4): 357-73. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=53793&dopt=Abstract

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Letter: Acetylcholine poisoning and sympathetic overactivity in tetanus. Author(s): Leonardi G. Source: Lancet. 1974 October 26; 2(7887): 1014-5. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=4138254&dopt=Abstract

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Local massage after vaccination enhances the immunogenicity of diphtheria-tetanuspertussis vaccine. Author(s): Hsu CY, Huang LM, Lee CY, Lin TY, Lee PI, Chen JM. Source: The Pediatric Infectious Disease Journal. 1995 July; 14(7): 567-72. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=7567283&dopt=Abstract

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Makwa (non-sterile skin cauterisation) as cause of tetanus. Author(s): Yagil Y, Heyman S.


Source: Lancet. 1982 May 1; 1(8279): 1027. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=6122843&dopt=Abstract •

Microtubules and microfilaments participate in the inhibition of synaptosomal noradrenaline release by tetanus toxin. Author(s): Ashton AC, Dolly JO. Source: Journal of Neurochemistry. 1997 February; 68(2): 649-58. Erratum In: J Neurochem 1997 May; 68(5): 2225. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=9003052&dopt=Abstract

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Naturally acquired antibodies to tetanus toxin in humans and animals from the galapagos islands. Author(s): Veronesi R, Bizzini B, Focaccia R, Coscina AL, Mazza CC, Focaccia MT, Carraro F, Honningman MN. Source: The Journal of Infectious Diseases. 1983 February; 147(2): 308-11. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=6827147&dopt=Abstract

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Neonatal tetanus (St Kilda, 19th century) Author(s): Woody RC, Ross EM. Source: Lancet. 1989 June 10; 1(8650): 1339. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=2566876&dopt=Abstract

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Neonatal tetanus in Maputo, Mozambique. Part I. Hospital incidence and childbirth practices. Author(s): Cliff J. Source: Cent Afr J Med. 1985 January; 31(1): 9-12. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=3872719&dopt=Abstract

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Neonatal tetanus in Zaria, Northern Nigeria. Author(s): Osuhor PC. Source: Indian J Public Health. 1983 January-March; 27(1): 32-7. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=6654472&dopt=Abstract

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Neonatal tetanus. Author(s): Macaulay C. Source: Nurs Times. 1985 November 13-19; 81(46): 32-4. No Abstract Available. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=3853142&dopt=Abstract

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Neonatal tetanus--a simplified treatment and preventive measures. Author(s): Topley JM, Egullion C.

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Source: Cent Afr J Med. 1986 April; 32(4): 89-91. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=3791399&dopt=Abstract •

OH. treatment of tetanus toxin reduces its susceptibility to limited proteolysis with more efficient presentation to specific T cells. Author(s): Pernollet M, Villiers C, Gabert F, Drouet C, Colomb M. Source: Molecular Immunology. 1993 December; 30(18): 1639-46. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=8272077&dopt=Abstract

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Outbreak of tetanus among elderly women treated with sheep cell therapy. Author(s): Wyszynski DF, Kechichian M. Source: Clinical Infectious Diseases : an Official Publication of the Infectious Diseases Society of America. 1997 April; 24(4): 738. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=9145754&dopt=Abstract

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Oxygen under high pressure and experimental tetanus. Author(s): Allgood MA, Holmes DD. Source: Aerosp Med. 1967 February; 38(2): 169-70. No Abstract Available. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=6040342&dopt=Abstract

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Persistent neuro-muscular block after curarization in tetanus. Author(s): Kaeser HE, Muller HI. Source: Electroencephalography and Clinical Neurophysiology. 1968 October; 25(4): 397. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=4176562&dopt=Abstract

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Pharmacotherapy of tetanus--a review. Author(s): Reddy VG. Source: Middle East J Anesthesiol. 2002 February; 16(4): 419-42. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11949205&dopt=Abstract

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Philosophic objection to vaccination as a risk for tetanus among children younger than 15 years. Author(s): Fair E, Murphy TV, Golaz A, Wharton M. Source: Pediatrics. 2002 January; 109(1): E2. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11773570&dopt=Abstract

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Properties of purified tetanus toxin and toxoid. Author(s): Raynaud M, Turpin A, Bizzini B. Source: Prog Immunobiol Stand. 1969; 3: 244-7. No Abstract Available. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=4985511&dopt=Abstract


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Proteolytic fragmentation of tetanus toxin by subcellular fractions of JY, a B lymphoblastoid cell line. Author(s): Reboul A, Arvieux J, Wright JF, Colomb MG. Source: The Biochemical Journal. 1991 July 1; 277 ( Pt 1): 47-51. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=1649603&dopt=Abstract

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Quaternary structure of botulinum and tetanus neurotoxins as probed by chemical cross-linking and native gel electrophoresis. Author(s): Ledoux DN, Be XH, Singh BR. Source: Toxicon : Official Journal of the International Society on Toxinology. 1994 September; 32(9): 1095-104. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=7801345&dopt=Abstract

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Report of a severe case of tetanus managed with large doses of intramuscular succinylcholine. Author(s): Curran FJ, Smith WE, Lauro S. Source: Anesthesia and Analgesia. 1968 May-June; 47(3): 218-21. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=4172446&dopt=Abstract

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Role of biogenic amines in tetanus. Author(s): Dastur FD, Prabhu G, Nair KG, Sheth UK. Source: J Assoc Physicians India. 1981 March; 29(3): 211-7. No Abstract Available. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=6115850&dopt=Abstract

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Serotonin transport is modulated differently by tetanus toxin and growth factors. Author(s): Gil C, Najib A, Aguilera J. Source: Neurochemistry International. 2003 June; 42(7): 535-42. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12590935&dopt=Abstract

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Severe tetanus: its complications and management. Author(s): Purkis IE, Curtis JE. Source: Can Med Assoc J. 1965 December 4; 93(23): 1200-4. No Abstract Available. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=5842593&dopt=Abstract

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Tetanus after induced abortion--a case report. Author(s): bin Misiran K. Source: Med J Malaysia. 1990 December; 45(4): 349-52. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=2152060&dopt=Abstract

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Tetanus mimicking psychophysiologic reaction. Occurrence after dental extraction. Author(s): Treadway CR, Prange AJ Jr.

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Source: Jama : the Journal of the American Medical Association. 1967 June 5; 200(10): 891-2. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=6071626&dopt=Abstract •

Tetanus toxin light chain cleaves a vesicle-associated membrane protein (VAMP) isoform 2 in rat pancreatic zymogen granules and inhibits enzyme secretion. Author(s): Gaisano HY, Sheu L, Foskett JK, Trimble WS. Source: The Journal of Biological Chemistry. 1994 June 24; 269(25): 17062-6. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=7516331&dopt=Abstract

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Tetanus toxin modulates serotonin transport in rat-brain neuronal cultures. Author(s): Pelliccioni P, Gil C, Najib A, Sarri E, Picatoste F, Aguilera J. Source: Journal of Molecular Neuroscience : Mn. 2001 December; 17(3): 303-10. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11859926&dopt=Abstract

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Tetanus; a study of 2,007 cases. Author(s): PATEL JC, MEHTA BC. Source: Indian Journal of Medical Sciences. 1963 October; 17: 791-811. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=14069728&dopt=Abstract

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The heavy chain of tetanus toxin can mediate the entry of cytotoxic gelonin into intact cells. Author(s): Johnstone SR, Morrice LM, van Heyningen S. Source: Febs Letters. 1990 June 4; 265(1-2): 101-3. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=2365046&dopt=Abstract

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The properties of sulfite-treated tetanus toxin. Author(s): Dawson DJ. Source: Febs Letters. 1975 August 1; 56(1): 175-8. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=808427&dopt=Abstract

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The traditional birth attendant and neonatal tetanus: the Malaysian experience. Author(s): Chen PC. Source: J Trop Pediatr Environ Child Health. 1976 December; 22(6): 263-4. No Abstract Available. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=1051832&dopt=Abstract

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The use of oral dehydroepiandrosterone sulfate as an adjuvant in tetanus and influenza vaccination of the elderly. Author(s): Evans TG, Judd ME, Dowell T, Poe S, Daynes RA, Araneo BA.


Source: Vaccine. 1996 November; 14(16): 1531-7. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=9014295&dopt=Abstract •

Traditional midwives, tetanus immunization, and infant mortality in rural Haiti. Author(s): Berggren GG, Berggren W, Verly A, Garnier N, Peterson W, Ewbank D, Dieudonne W. Source: Trop Doct. 1983 April; 13(2): 79-87. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=6679403&dopt=Abstract

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Treating severe tetanus with muscle paralysis and intermittent positive pressure ventilation. Author(s): Sykes K. Source: European Journal of Anaesthesiology. 1998 May; 15(3): 380. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=9650004&dopt=Abstract

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Treatment of tetanus in intensive care unit. Author(s): Patel JC, Singhania SK. Source: J Assoc Physicians India. 1978 September; 26(9): 857-9. No Abstract Available. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=284004&dopt=Abstract

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Treatment of the patient with severe tetanus. Author(s): Christensen NA. Source: The Surgical Clinics of North America. 1969 October; 49(5): 1183-93. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=5823335&dopt=Abstract

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Umbilical cord care and neonatal tetanus. Author(s): Oudesluys-Murphy AM. Source: Lancet. 1989 April 15; 1(8642): 843. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=2564924&dopt=Abstract

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Uvulectomy as an epidemiological factor in neonatal tetanus mortality:- observations from a cluster survey. Author(s): Eregie CO. Source: West Afr J Med. 1994 January-March; 13(1): 56-8. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=8080834&dopt=Abstract

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Zinc supplementation stimulates tetanus antibody formation and soluble interleukin2 receptor levels in chronic hemodialysis patients. Author(s): Holtkamp W, Brodersen HP, Stollberg T, Thiery J, Falkner C. Source: Clin Investig. 1993 July; 71(7): 537-41. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=8374246&dopt=Abstract

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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 tetanus; 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 Asthma Source: Healthnotes, Inc.; www.healthnotes.com Burns Source: Integrative Medicine Communications; www.drkoop.com Frostbite Source: Integrative Medicine Communications; www.drkoop.com Immune Function Source: Healthnotes, Inc.; www.healthnotes.com Rubella Source: Integrative Medicine Communications; www.drkoop.com Serum Sickness Source: Integrative Medicine Communications; www.drkoop.com


Wounds Source: Integrative Medicine Communications; www.drkoop.com •

Chinese Medicine Baifuzi Alternative names: Giant Typhonium Rhizome; Rhizoma Typhonii Source: Chinese Materia Medica Chantui Alternative names: Cicada Slough; Periostracum Cicadae Source: Chinese Materia Medica Fangfeng Alternative names: Divaricate Saposhnikovia Root; Radix Saposhnikoviae Source: Chinese Materia Medica Fuzi Alternative names: Beivedere Fruit; Difuzi; Fructus Kochiae Source: Chinese Materia Medica Jinqian Baihuashe Alternative names: Coin-like White-banded Snake; Jinqian Baihuashe (Jin Qian Bai Hua She); Bungarus Parvus Source: Chinese Materia Medica Qishe Alternative names: Long-noded Pit Viper; Qishe (Qi She); Agkistrodon Source: Chinese Materia Medica Quanxie Alternative names: Scorpion; Scorpio Source: Chinese Materia Medica Tianma Alternative names: Tall Gastrodia Tuber; Rhizoma Gastrodiae Source: Chinese Materia Medica Tiannanxing Alternative names: Jackinthepulpit Tuber; Rhizoma Arisaematis Source: Chinese Materia Medica Wushaoshe Alternative names: Black-tail Snake; Zaocys Source: Chinese Materia Medica

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Herbs and Supplements Eleuthero Alternative names: Eleutherococcus senticosus, Acanthopanax senticosus Source: Healthnotes, Inc.; www.healthnotes.com

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Lobelia Source: The Canadian Internet Directory for Holistic Help, WellNet, Health and Wellness Network; www.wellnet.ca Piper Alternative names: Kava; Piper methysticum Forst.f 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 TETANUS Overview In this chapter, we will give you a bibliography on recent dissertations relating to tetanus. 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 “tetanus” (or a synonym) in their titles. To accurately reflect the results that you might find while conducting research on tetanus, we have not necessarily excluded non-medical dissertations in this bibliography.

Dissertations on Tetanus 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 tetanus. 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: •

Theoretical Binding Studies of the Clostridial Tetanus Toxin and the Ganglioside Gd1b by Buczko, Ellen Sara; PhD from The American University, 2002, 352 pages http://wwwlib.umi.com/dissertations/fullcit/3048279

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 TETANUS Overview In this chapter, we will show you how to keep informed of the latest clinical trials concerning tetanus.

Recent Trials on Tetanus The following is a list of recent trials dedicated to tetanus.8 Further information on a trial is available at the Web site indicated. •

Studies of Influenza Vaccine and Tetanus-Pneumococcal Vaccine in HIV-infected Patients Receiving Interleukin-2 Condition(s): HIV Infections Study Status: This study is currently recruiting patients. Sponsor(s): National Institute of Allergy and Infectious Diseases (NIAID) Purpose - Excerpt: This investigation is a sub-study of the 6-year multinational ESPRIT (Evaluation of Subcutaneous Proleukin in a Randomized International Trial) protocol. It will compare the effectiveness of the influenza (FLUVAC) and tetanus-pneumococcal (TEPVAC) vaccines in HIV-infected patients receiving interleukin-2 (IL-2) plus anti-HIV drugs with those receiving only anti-HIV drugs. IL-2 is a protein naturally produced by immune cells called lymphocytes. Lymphocytes from patients with HIV do not produce IL-2 normally. The ESPRIT trial is evaluating whether HIV-infected patients treated with antiretroviral drugs plus IL-2 have fewer serious infections and improved survival than those receiving only anti-HIV drugs. Participants in this sub-study will be drawn from patients enrolled in ESPRIT. They must be 18 years of age or older, have HIV infection with no symptoms of significant HIV illness. They will be vaccinated against either influenza or tetanus and pneumococcus, as follows: FLUVAC Potentially eligible patients will be screened for the FLUVAC study during an ESPRIT follow-up visit. Those who are eligible and agree to participate will have 10 ml (1 tablespoon) of blood drawn to assess baseline antibody levels and then receive the vaccination. They will be vaccinated annually for 3 years. A blood sample (10 ml) will be drawn 1 month after

8 These

are listed at www.ClinicalTrials.gov.

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each vaccination to measure the immune response. Some of the blood drawn for this study will be stored and used for research purposes. TEPVAC Participants will have 10 ml of blood drawn to assess their baseline antibody levels. They will receive two vaccinations (tetanus and pneumococcus) 12 months after enrolling in ESPRIT and another two vaccinations 24 months after enrollment. A blood sample (10 ml) will be drawn 1 month after each vaccination to measure the immune response. Some of the blood drawn for this study will be stored and used for research purposes. Phase(s): Phase II Study Type: Interventional Contact(s): see Web site below Web Site: http://clinicaltrials.gov/ct/show/NCT00050726 •

Vaccination with tetanus and KLH to assess immune responses. Condition(s): Cancer Study Status: This study is currently recruiting patients. Sponsor(s): National Center for Research Resources (NCRR) Purpose - Excerpt: The purpose of this study is to learn how the immune system works in response to vaccines. We will give the vaccines to subjects who have cancer but have not had treatment, and to patients who have had chemotherapy or stem cell transplant. Some patients will get vaccines while they are on treatments which boost the immune system (like the immune stimulating drug interleukin-2 or IL-2). Although we have safely treated many patients with immune boosting drugs, we do not yet know if they improve the body's immune system to respond better to a vaccine. Some healthy volunteers will also be given the vaccines in order to serve as control subjects to get a good measure of the normal immune response. We will compare the patients and the healthy volunteers to study how their immune systems respond to the vaccines. There are several different types of white cells in the blood. We are interested in immune cells in the blood called T-cells. These T-cells detect foreign substances in the body (like viruses and cancer cells). We are trying to learn more about how the body fights these foreign substances. Our goal is to develop cancer vaccines which would teach T-cells to detect and kill cancer cells better. We know that in healthy people the immune system effectively protects against recurrent virus infection. For example, that is why people only get "mono" (mononucleosis) once under normal circumstances. When the body is infected with the "mono" virus, the immune system remembers and prevents further infection. We are trying to use the immune system to prevent cancer relapse. To test this, we will give two vaccines which have been used to measure these immune responses. Blood samples will be studied from cancer patients and will be compared to similar samples from normal subjects. Study Type: Observational Contact(s): see Web site below Web Site: http://clinicaltrials.gov/ct/show/NCT00000105

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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 “tetanus” (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/

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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

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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 TETANUS 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 “tetanus” (or a synonym) in their titles. To accurately reflect the results that you might find while conducting research on tetanus, we have not necessarily excluded non-medical patents in this bibliography.

Patents on Tetanus By performing a patent search focusing on tetanus, 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 tetanus: •

[Gln']-luteinizing hormone releasing hormone conjugate of tetanus vaccine and its uses Inventor(s): Ladd; Anna E. (New York, NY), Thau; Rosemarie B. (New York, NY), Tsong; Yun-Yen (North Caldwell, NJ) Assignee(s): The Population Council (New York, NY) Patent Number: 5,324,512 Date filed: December 26, 1990 Abstract: The present prevention provides an effective, fast acting method of vaccination useful in suppressing gonadotropic hormone release. The vaccine utilizes LHRH conjugated at its amino terminus to a protein carrier and can be mixed with either adjuvants or detergents in order to provide an effect vaccine. Excerpt(s): The possibility of developing an antifertility vaccine for male mammals based on active immunization against Luteinizing Hormone Releasing Hormone (LHRH) is currently under investigation in several laboratories. These studies are based on the findings that antibodies against LHRH prevent gonadotropin release. Prevention of gonadotropin release causes regression of Leydig cells and suppression of testosterone production and spermatogenesis with subsequent infertility. See e.g. Fraser et al., "Effect of Active Immunization to Luteinizing Hormone Releasing Hormone on Serum and Pituitary Gonadotropins, Tests and Accessory Sex Organs in Male Rat", J. Endocrinol., 63:399-405 (1974); Fraser et al., "LHRH Antibodies: Their Use in the Study of Hypothalamic LHRH and Testicular LHRH-like Material, and Possible Contraceptive Applications", In: Sandlet, ed Progress Toward a Male Contraceptive. New York, John Wiley, (1982) pp. 41-78. Production of anti-LHRH antibodies would also be useful to treat certain forms of cancer such as prostate cancer where such therapy could replace orchiectomy or LHRH analogue treatment. Recurrent or metastatic cancer of the prostate is a major cause of cancer mortality in the United States with more than 25,000 deaths occurring annually because of this malignancy. Silverberg and Lubera, "Cancer Statistics", CA 38:1-19 (1988). It is the most common malignancy in men older than 70. Carcinoma within the prostate is a common finding at autopsy, being found in 20-40% of men between 70-79 years of age. Unfortunately, approximately one third of all prostate cancers are diagnosed only after the patient has clinically apparent disseminated disease with bone or visceral metastases outside the pelvis. Web site: http://www.delphion.com/details?pn=US05324512__

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Anti immune complex antibody for determining SLE, rheumatoid arthritis or tetanus Inventor(s): Kasahara; Yasushi (Tokyo, JP), Soma; Kazunori (Tokyo, JP) Assignee(s): Fujizoki Pharmaceutical Co., Ltd. (Tokyo, JP) Patent Number: 4,544,640 Date filed: April 7, 1983 Abstract: An antibody is obtained by using as an antigen a complex of an antigen and the F(ab').sub.2 fragment of the human antibody of this antigen or an aggregate of the F(ab').sub.2 fragment of human immunoglobulin. This antibody reacts with an immune

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complex in a blood serum of a patient of systemic lupus erythematosus and with an immune complex in a blood serum of a patient of rheumatoid arthritis, and it does not react with an aggregated IgG. The amount of immune complex in a blood serum is easily and exactly determined by using this antibody. Excerpt(s): This invention related to a novel antibody capable of detecting an immune complex and relates to its preparation method and use. Immune complex is the combined product of an antigen, an antibody and a complement. When this immune complex is formed in a human body, the immune complex is usually rendered harmless by a leucocyte or a macrophage. However, when a large quantity of antigen exists in a human body, or when an antigen the antibody of which forms with difficulty, exists in a human body, the amount of immune complex increases, and it causes various diseases such as acute glomerulonephritis, angitis, chronic urticaria, and thrombocytopenia. Various measuring methods of this immune complex are known such as the method utilizing a reaction of complement or rheumatoid factor with the immune complex, the method utilizing a reaction of the Fc receptor with the immune complex, and various physicochemical methods such as the gel filtration method, the sucrose density gradient centrifuge and precipitation with polyethyleneglycol. However, the method using the complement or rheumatoid factor and the method using Fc receptor have a fatal defect in that these methods cannot distinguish between aggregated IgG and the immune complex. The physicochemical methods are complicated and they are insufficient in specificity. Web site: http://www.delphion.com/details?pn=US04544640__ •

Atoxic, immunogenic product of tetanus toxin Inventor(s): Helting; Torsten B. (Marburg an der Lahn, DE) Assignee(s): Behringwerke Aktiengesellschaft (Marburg an der Lahn, DE) Patent Number: 4,200,627 Date filed: December 21, 1978 Abstract: What is disclosed is a method for obtaining an atoxic, immunogenic product from tetanus toxin by treating tetanus toxin with a proteinase. The product, which is different from known fragment C of tetanus toxin, can be used for making a vaccine. Excerpt(s): The present invention relates to an atoxic, immunogenic product of tetanus toxin. The invention provides an atoxic, immunogenic product which may be obtained from tetanus toxin by means of a proteinase. It also provides a tetanus vaccine containing the novel product. As has already been known, tetanus toxin is highly toxic towards mammals and also humans and must be detoxicated, in order to be used as an immunizing agent. It has been known to detoxicate tetanus toxin by treating it with formaldehyde. It has also been known that an atoxic, immunogenic product can be obtained by a treatment of tetanus toxin with a proteinase. This atoxic, immunogenic product is called fragment C of the tetanus toxin in the scientific literature. Web site: http://www.delphion.com/details?pn=US04200627__

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Compositions and methods for chemodenervation using neurotoxins Inventor(s): First; Eric R. (52 N St. South, Boston, MA 02127-2305), Pearce; L. Bruce (16 Partridge Cir., Hudson, NH 03051) Assignee(s): none reported Patent Number: 6,087,327 Date filed: January 30, 1998 Abstract: The compositions and methods disclosed herein utilize admixtures of neurotoxins to cause denervation which is unexpectedly more localized and of longer duration than otherwise occurs with single neurotoxins. The compositions and methods of the invention utilize neurotoxin admixtures calibrated in median paralysis units rather than LD.sub.50 s. Admixtures of neurotoxins include, but are not limited to, the botulinum serotypes A-G and tetanus toxin. The clinical benefits of the disclosed invention include: lengthening intervals between neurotoxin treatments; reducing adverse immunogenic responses to neurotoxins; and, reducing adverse diffusiondependent side-effects of neurotoxin treatments. Excerpt(s): The present invention relates generally to compositions and methods for chemodenervation using admixtures of neurotoxin. Botulinum neurotoxin is a Clostridial neurotoxin that produces flaccid paralysis by irreversibly inhibiting the release of acetylcholine (ACh) from nerve terminals at the motor endplate. While this ACh-related phenomenon has been well documented and is generally considered its primary mechanism of action, numerous researchers have evidence that botulinum neurotoxins may also act by impairing or inhibiting vesicular release of other neurotransmitters and/or neuroactive substances. See, e.g., Ashton et al. (1988) 50 J.Neurochemistry 1808; McMahon et al. 267 J.Biol.Chem. 21388; Blasi et al. (1994) 88 J.Physiol. 235. The profound specificity of action of botulinum neurotoxin has contributed to the fact that this neurotoxin has become widely employed for its therapeutic potential in the treatment of a variety of involuntary movement disorders (Borodic et al. (1991), 4 Opthalmology Clinics of North America 491-504; Hambelton, P. (1992), 239 J. Neurol. 16-20; Schantz et al. (1992), 50 Microbiol. Rev. 1:80-99; Valtorta et al. (1993), 27 Pharmacol. Res. 1:33-44). Intramuscular injection of nanogram quantities of purified botulinum neurotoxin is the treatment of choice for a number of clinical indications including: blepharospasm, spasmodic dysphonia, hemifacial spasm, and adult onset spasmodic torticollis. Botulinum neurotoxin therapy has primarily involved intramuscular injection of the serotype A, however, the F and B serotypes are currently also considered clinically relevant (Greene et al. (1993), Botulinum and Tetanus Neuroneurotoxins (ed. B. R. DasGupta, Plenum Press, New York pp. 651-654). These additional serotypes hold the promise of alternative therapies for patients that develop resistance to the A neurotoxin. Moreover, these neurotoxins may also possess intrinsic properties that result in significant therapeutic advantages. Web site: http://www.delphion.com/details?pn=US06087327__

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Expression of tetanus toxin fragment C Inventor(s): Fairweather; Neil F. (Langley Court, Beckenham, Kent, GB), Makoff; Andrew J. (Langley Court, Beckenham, Kent, GB) Assignee(s): none reported Patent Number: 5,443,966 Date filed: August 23, 1993 Abstract: The present invention relates to an expression vector encoding mature fragment C of tetanus toxin. The invention further relates to an E. coli host transformed by that vector and to a process for producing mature fragment C of tetanus toxin using same. Excerpt(s): The present invention relates to the production of tetanus toxin C fragment. E. coli has been successfully used as an host in which many foreign proteins have been obtained in large amounts. However, it has been found that the foreign protein is generally produced in an insoluble form, despite being soluble in its native environment (J.Biochem., 1986, 240, 1-12). When viewed by a microscope under phase contrast conditions, the protein aggregates are visible within the bacterial cells and are usually referred to as inclusion or refractile bodies. It is relatively straightforward on a laboratory scale to separate inclusion bodies from the majority of E. coli proteins. This can be achieved for example by centrifugation and can lead to remarkable purification in just one step. However, on an industrial scale purification of the inclusion bodies is difficult to perform. In any event, to obtain the protein in an active form, the inclusion bodies have to be solubilized, requiring the use of strong denaturing agents such as urea or guanidinium chloride. The denaturant is then removed under conditions which allow the protein to refold into its native conformation. These conditions are established empirically for each protein and frequently involve the use of very dilute solutions, which on scale-up can lead to enormous volumes and consequent process engineering problems. These difficulties can be offset to some extent by the high productivity of E. coli, but clearly it would be desirable to obtain this benefit with the production of the protein in soluble form. Web site: http://www.delphion.com/details?pn=US05443966__

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Expression of tetanus toxin fragment C in yeast Inventor(s): Clare; Jeffrey J. (Beckenham, GB2), Fairweather; Neil F. (Beckenham, GB2), Makoff; Andrew J. (Beckenham, GB2), Romanos; Michael A. (Beckenham, GB2) Assignee(s): Evans Medical Limited (Leatherhead, GB) Patent Number: 5,389,540 Date filed: November 27, 1990 Abstract: Expression of tetanus toxin fragment C is accomplished employing a DNA coding sequence having a (G+C)-content that has been increased in the region from nucleotide 410 to the 3' end of the coding sequence relative to the wild-type DNA sequence. This allows the production of complete mRNA transcripts. Typically the (G+C)-content is increased in the following regions: (i) nucleotides 510-710, (ii) nucleotides 650-850, (iii) nucleotides 800-1100, (iv) nucleotides 900-1200 and (v) nucleotides 1100 to the 3' end of the coding sequence. The (G+C)-content may also be

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increased in the region of nucleotides 410-610. These regions in the wild-type DNA encompass terminator sequences. Excerpt(s): The present invention relates to the production of tetanus toxin C fragment. Vaccination against tetanus is effective in the prevention of this disease in most Western countries, although incomplete vaccination in some third world countries can account for up to one million cases of tetanus every year. Current tetanus vaccines are produced by formaldehyde treatment of tetanus toxin produced by the anaerobic bacterium C. tetani to produce the immunogenic toxoid. It has been suggested that impurities incorporated during formaldehyde treatment are partly responsible for the adverse effects sometimes seen with hyperimmunisation with tetanus toxoid. The structural gene for tetanus toxin has been cloned and sequenced (Fairweather, N. F., et al, J. Bacteriol. 165, 21-27 (1986); Fairweather, N. F., and Lyness, V. A., Nuc. Acid Res. 14, 7809-7812 (1986). These studies have confirmed the structure of tetanus toxin as a 150kD protein of 1315 amino acids. The toxin can be cleaved by various treatments into several fragments. Fragment C, comprising the C terminal 451 amino acids, is a 50kD polypeptide generated by papain cleavage of toxin. Web site: http://www.delphion.com/details?pn=US05389540__ •

Glycoproteinic conjugates having trivalent immunogenic activity Inventor(s): Costantino; Paolo (Colle Val d'Elsa, IT), Porro; Massimo (Localita' Collanza, IT) Assignee(s): Sclavo S.p.A. (Siena, IT) Patent Number: 4,711,779 Date filed: July 2, 1986 Abstract: Glycoproteinic conjugates having trivalent immunogenic activity obtained by binding, by a covalent bond, to a protein selected among CRM 197, tetanus toxoid, and pertussis toxin, at least an oligosaccharidic hapten derived from the capsular polysaccharide of a gram-positive bacterium and at least an oligosaccharidic hapten derived from the capsular polysaccharide of a gram-negative bacterium, and wherein said oligosaccharidic haptens are previously activated by introducing terminal esters. Excerpt(s): The present invention relates to glycoproteinic conjugates having trivalent immunogenic activity, to their preparation, and to their use as vaccines. In particular, the present invention relates to glycoproteinic conjugates having trivalent immunogenic activity obtained by binding, by a covalent bond, to a protein selected among CRM 197, tetanus toxoid and pertussis toxin, at least one oligosaccharidic hapten derived from the capsular polysaccharide of a gram-positive bacterium, and at least one oligosaccharidic hapten derived from the capsular polysaccharide of a gram-negative bacterium, after the preliminary activation of said oligosaccharidic haptens by the introduction of terminal ester groups. The development of vaccines against such capsulate bacteria as meningococcus and pneumococcus by the use of capsular polysaccharidic antigens derived from said bacteria, has shown the poor immunogenicity of said polysaccharidic anitgens, above all in infantile population. Web site: http://www.delphion.com/details?pn=US04711779__

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Group B streptococcus type II polysaccharide-tetanus toxoid conjugate vaccines Inventor(s): Jennings; Harold J. (Gloucester, CA), Kasper; Dennis L. (Newton Centre, MA) Assignee(s): Brigham and Women's Hospital, Inc. (Boston, MA), National Research Council of Canada (Ottawa, CA) Patent Number: 5,843,461 Date filed: August 22, 1997 Abstract: This invention relates to antigenic conjugate molecules comprising the capsular polysaccharide of Group B streptococcus type II which are covalently linked to protein. This invention also relates to vaccines and methods of immunizing mammals, including humans against infection by Group B streptococcus type II (GBS II). Multivalent vaccines comprising the conjugate molecules of this invention and antigens to other pathogenic bacteria are also claimed. Excerpt(s): Infections due to group B streptococci (GBS) are the most common single cause of sepsis and meningitis in newborns in developed countries (3, 31). Recent reports from some centers in the United States reflect a lower mortality (9 to 13%) than in series from the 1970s, perhaps as a result of earlier diagnosis and intensive care (1, 10). Nonetheless, fatal infections still occur, and equally important, up to 50% of survivors of GBS meningitis have chronic neurologic injury ranging from deafness and mild learning disabilities to profound motor, sensory, and cognitive impairment (3). Prevention rather than improved diagnosis or therapy is likely to have the most significant impact in further reducing GBS-related morbidity and mortality. Because GBS capsular polysaccharide-specific antibodies appear to protect both experimental animals (23, 24) and human infants (4, 5) from GBS infection, some of the polysaccharides have been purified and tested in healthy adults as experimental vaccines (6). Were a safe and efficacious GBS vaccine available, it could be administered to women before or during pregnancy to elicit antibodies that would transfer to the fetus in utero and provide protection against neonatal infection. Of the three GBS polysaccharides (types Ia, II, and III) tested in volunteers, type II had the highest rate of immunogenicity, eliciting a type II-specific antibody response in 88% of previously nonimmune recipients (6). In neonates, the level of specific antibody required for protection against type II GBS infection is not precisely defined but has been estimated at 2 or 3.mu.g/ml (6). In a vaccine recipient who achieves an antibody response only slightly above the minimum required for protection, the amount of maternal antibody transferred across the placenta may be inadequate to protect a premature infant, because of the incomplete transfer to the fetus of material immunoglobulin G (IgG), or an infant with late-onset infection, since the half-life of maternal IgG antibodies in the newborn is about 25 days (13). Many of the infants in these two groups of patients might be protected if the magnitude of the specific antibody response to vaccination were higher. The transfer of maternal IgG to the fetus increases throughout the third trimester, so a higher maternal antibody level would provide protection earlier, i.e., to a more premature infant (16). Similarly, higher maternal levels would result in longer persistence of maternal antibodies in the infant, thereby providing protection against late-onset disease, as well. Web site: http://www.delphion.com/details?pn=US05843461__

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Human lymphoblastold cell line and hybridomas derived therefrom Inventor(s): Larrick; James W. (Woodside, CA), Raubitschek; Andrew R. (Palo Alto, CA), Truitt; Kenneth E. (San Diego, CA) Assignee(s): Cetus Corporation (Emeryville, CA) Patent Number: 4,624,921 Date filed: April 26, 1984 Abstract: A 6-thioguanine-resistant subvariant of the EBV-transformed human lymphoblastoid B cell line WI-L2 is described. The subvariant line, designated LTR228, fuses efficiently with human cells. Human.times.human hybridomas derived from LTR228 that produce monoclonal antibodies against tetanus toxin and blood group A are exemplified. Excerpt(s): This invention is in the field of biotechnology and relates to somatic cell hybridization and immunochemistry. More particularly, it concerns a novel EpsteinBarr virus (EBV)-transformed human lymphoblastoid fusion partner, human.times.human hybridomas made with that lymphoblastoid line, and human monoclonal antibodies produced by those hybridomas. Kohler, B. and Milstein, C., Nature (1975) 256:495-497, pioneered the use of somatic cell hybridization to make continuous hybridomas that produce monoclonal antibodies. Their work used plasmacytomas and lymphocytes of murine origin. Subsequent investigators have reported applying Kohler and Milstein's techniques to human cells. Croce, C. M., et al, Nature (Lond) (1980) 288:488 and Olsson, L. and Kaplan, H. S., PNAS (USA) (1980) 77:5429. Steinwitz, M., et al, Nature (1977) 269:420 and Luzzanti, A. G., et al, Nature (1977) 269:419 describe in vitro production of specific human antibodies from EBVtransformed human B lymphoblastoid cells. While the EBV transformation allowed these cells to be grown continuously, the cells typically lose their ability to secrete Ig in a short period of time. Several recent references describe using EBV-transformed human lymphoblastoid cell lines as parental tumor partners in fusions with Ig-producing human lymphocytes. European patent application No. 82301103.6 published 13 October 1982 describes such a line designated WI-L2-729 HF.sub.2. This line is reported to be a hypoxanthine phosphoribosyl transferase (HPRT) deficient variant of the WI-L2 line (Levy, J. A., et al, Cancer (1968) 22:517). It is characterized as being nonsecreting, sIgM.kappa.+, cyIgM.kappa.+, and able to grow in serum-free media. Chiorazzi, N., et al, J Exp Med (1982) 156:930-935 describes another EBV-transformed human lymphoblastoid cell line derived from the WI-L2 line. This other line, designated H35.1.1, appears to have different characteristics than the WI-L2-729 HF.sub.2 line. Handley, H. H., et al, Proceedings of the 15th International Leucocyte Culture Conference, Asilomar (1982), p. 267, describes an intermediate parent of the WI-L2-729 HF.sub.2 line, designated UC729-6. UC 729-6 is reported to have characteristics common to WI-L2-729 HF.sub.2 and was used as a fusion partner in making Ig-producing human.times.human hybridomas. Web site: http://www.delphion.com/details?pn=US04624921__

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Human monoclonal antibodies against bacterial toxins Inventor(s): Gigliotti; Francis (Memphis, TN), Insel; Richard A. (Rochester, NY) Assignee(s): University of Rochester (Rochester, NY) Patent Number: 4,689,299 Date filed: September 22, 1983 Abstract: The production of stable hybrid cell lines that secrete human monoclonal antibodies against bacterial toxins by fusing post-immunization human peripheral blood lymphocytes with nonsecretor mouse myeloma cells is described. Using the method, protective monoclonal antibodies against tetanus toxin and diphtheria toxin were produced that bind tetanus toxin and diphtheria toxin in vitro, respectively, and prevent tetanus and diphtheria in vivo in animals, respectively. Excerpt(s): This invention relates to the production of and applications for antibodies specific for bacterial toxins and, in particular, for tetanus toxin and diphtheria toxin. This invention further relates to the production of human monoclonal antibodies against bacterial toxins by fused cell hybrids. A bacterial toxin may be defined as a chemical substance produced by bacteria that damages the host if it reaches susceptible tissues. Tetanus is an nfectious disease caused by the neurotoxin of Clostridium tetani which poses a serious health problem worldwide despite efforts to control the disease through pre-infection immunization programs. Diphtheria is an infectious disease caused by the exotoxin of lysogenic strains of Corynebacterium diphtheriae. While this disease is controlled in countries such as the U.S. where mass immunization of the population is practiced, it still poses a health threat in those countries where immunization programs are rare. The anti-tetanus toxin and anti-diphtheria toxin human monoclonal antibodies of the present invention can neutralize tetanus toxin and diphtheria toxin, respectively. They can prevent tetanus and diphtheria disease, and hence represent new chemotherapeutic agents for the prevention and/or treatment of toxin-induced diseases. The invention provides a method for fusing post-immunization human peripheral blood lymphocytes with non-secretor mouse myeloma cells to produce stable fused cell hybrids secreting human antibodies against bacterial toxins. Once cloned, these cell lines can be maintained continuously to produce an unlimited homogeneous monoclonal antibody population that can be isolated and used clinically for diagnosis, immunoprophylaxis and immunotherapy, for production and purification of vaccines, as well as for other research purposes. Kohler and Milstein demonstrated in 1975 that antibody-producing cell lines could be produced by somatic cell hybridization, a process by which lymphocytes and myelomas are fused into single cells and cloned [G. Kohler and C. Milstein, Nature 256:495-497 (1975)]. The resulting cell lines, termed "hybridomas", retain the antibody-secreting capacity of the parental lymphocyte and, at the same time, gain the immortality of the parental myeloma cell line, that is, the ability to reproduce themselves indefinitely. With this combination of features, hybridomas produce unlimited homogeneous antibody (monoclonal antibody) that can be selected for desired specifically and biologic activity. Monoclonal antibodies are replacing conventional antisera in diagnostic laboratories and are providing new insights in medicine [R. H. Kennett, T. J. McKearn and K. B. Bechtol (editors), Monoclonal antibodies, Plenum Press, New York (1980); D. E. Yelton and M. D. Scharff, Ann. Rev. Biochem. 50:657-680 (1981); and M. S. Mitchell and H. F. Oettgen (editors), Hybridomas in the diagnosis and treatment of cancer, Progress in cancer research and therapy, Vol. 21, Raven Press, (1982)]. Monoclonal antibodies produced by hybrid cell lines have potential use in many areas of medicine including therapy of human infection, malignancy, and transplantation rejection.

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Web site: http://www.delphion.com/details?pn=US04689299__ •

Immunogenic polysaccharide-protein conjugates Inventor(s): Jennings; Harold J. (Ottawa, CA), Lugowski; Czeslaw (Wroclaw, PL) Assignee(s): Canadian Patents & Development Ltd. (Ottawa, CA) Patent Number: 4,356,170 Date filed: May 27, 1981 Abstract: Antigenic polysaccharides are modified to generate a terminally-located aldehyde group by controlled oxidation of vicinal hydroxyl groups, e.g. of unlinked terminal non-reducing sialic acid residues. In some cases where there is a reducing end group, e.g. of the type N-acetylmannosamine residue, it can be made into the most susceptible site for oxidation by initially reducing it to its open chain hydroxyl form, e.g. N-acetylmannosaminitol. The vicinal hydroxyl oxidation is controlled to yield a reactive aldehyde group which is then covalently linked to a free amino group of a selected protein by reductive amination. The resulting polysaccharide-protein conjugates are soluble and have been found to have enhanced antigenicity compared to the polysaccharide alone. This terminal aldehyde:free amine group reductive amination can be applied to various polysaccharide antigens and various well-tolerated proteins, preferably protein immunogens. For example, meningococcal group A, B and C polysaccharides have been linked to tetanus toxoid to give soluble conjugates which have been found to have advantageous immunogenic properties. Excerpt(s): This invention relates to antigenic polysaccharide-protein conjugates, their preparation and use as vaccines. A novel conjugate linkage has been utilized which minimizes cross-linking and gives a soluble conjugate. Animal tests have shown enhanced immunogenic properties for the conjugate compared to the initial polysaccharide antigen. The resulting vaccines are particularly suitable for immunizing human infants against infections, the immune response for which is non-thymuscontrolled. Polysaccharides, particularly the capsular polysaccharides from bacteria such as Neisseria meningitidis, have been used with some success in providing homologous serogroup immunity. Meningococcal polysaccharide group A and C are relatively poor immunogens in human infants, and group B is only poorly immunogenic in man. The poor results with infants is highly undesirable since this section of the population has the highest incidence of these infections. In order to surmount these problems with infants and to expand the usefulness of polysaccharide vaccines, it is necessary to enhance the immunogenicity. One possible method of achieving this objective, which has shown some promise, is to conjugate these polysaccharides to a carrier protein. Several instances of this approach have been reported but the coupling methods employed resulted in linkages having highly undesirable structural features for use in human vaccines. (3) R. J. Fielder, C. T. Bishop, S. F. Grappel, and F. Blank, "An immunogenic polysaccharide-protein conjugate", J. of Immunol. 105, 265, 1970. Web site: http://www.delphion.com/details?pn=US04356170__

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Immunological preparations Inventor(s): Allison; Anthony Clifford (London, EN), Gregoriadis; Gregory (Kenton, EN) Assignee(s): National Research Development Corporation (EN) Patent Number: 4,053,585 Date filed: June 25, 1975 Abstract: Immunological preparations are described in which liposomes having a negative charge are used as adjuvants for the purposes of human and veterinary vaccines containing viral or bacterial antigens. The formulation of influenza antigen, and diphtheria and tetanus toxoid antigens in liposomes formed with egg lecithin is described and the adjuvant effect demonstrated. Excerpt(s): This invention relates to immurological preparations including antigenic compositions e.g. viral and bacterial vaccines and antibody preparations, and is more particularly concerned with immunological preparations containing adjuvants. Adjuvants are substances that enhance the immune response of a specific antigen. Examples of adjuvants are Freund's incomplete adjuvant, a water-in-oil emulsion containing the antigen, and Freund's complete adjuvant, which is the same with killed tubercle bacilli. Unfortunately, the mineral oils currently available for use as adjuvants are not readily degraded in man and persist at the injection site thereby causing unacceptable granulomas or other undesirable effects. There is however a real need for a safe and effective adjuvant for use in human immunization programmes. Such an adjuvant could reduce the amounts of antigens, e.g. diptheria and tetanus toxoids, required for protective immunization, with corresponding economies especially relevant to the developing countries. The need for improved adjuvants in veterinary vaccines also exists. Furthermore, it is desirable to administer as many vaccines as possible at the same time, so that one or a few injections can immunize humans or animals against a wide range of organisms or their toxic products. This is especially relevant to tropical countries where, in addition to the infections of temperate climates, there is exposure to many parasitic infections. When two or more antigens are administered simultaneously, each may reduce the formation of antibodies against the other, by a phenomenon known as antigenic competition. In addition the choice of suitable adjuvant materials is also controlled by the need to avoid allergic reactions. Web site: http://www.delphion.com/details?pn=US04053585__

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Impact and speed measuring system Inventor(s): Josephson; Daniel M. (6710 Escondido Dr., Houston, TX 77083), Winn; Donald G. (6710 Escondido Dr., Houston, TX 77083) Assignee(s): none reported Patent Number: 4,941,660 Date filed: September 2, 1988 Abstract: A high-speed, portable computer interfaced, fluid-filled, foam-padded, heavy bag with local electronic force indicator is provided along with a mechanically-driven paper chart recorder with digital output, split screen video data recording system, and printer for automatic data analysis used to measure a fighter's individual, peak, and total applied force on a target. Such target is constructed so that the fighter feels both familiar and comfortable for each hit, each session, and for such fighter's entire training

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career spent practicing a bag connected in the system of the present invention. Such system is accurate enough to determine at which point a fighter'punching or kicking muscle groups undergo initial fatigue and subsequent tetanus, or tightening. Excerpt(s): A system is provided for measuring, recording, and reviewing the activities associated with martial arts such as boxing or contact sports, such as football training. Such system records peak force and the total applied force to a bag such as a boxing bag. Previous art devices claimed to measure total applied force, but in scientific fact, did not. The bag has a transducer connected to indicator means which records the speed, power and endurance of punches to the bag. A split screen video component allows viewing of the person punching the bag and also allows viewing of a paper chart recorder which is part of the indicator means. The system is unique in that total applied force is measured and recorded along with the frequency of impact while simultaneously providing video display of the person punching the bag. The output signal from the electronic indicator 52 is connected through conductor 54 to a mechanical drive, digital output, paper chart recorder 56 equipped with a desk top computer interface port for interface with a desk top computer having similar interface port and data analysis and record keeping programs. Another channel is provided to accommodate pulse and respiration data simultaneous with the applied force data for comparison of the relation between them. A digitized signal from chart recorder 56 and from electronic indicator 52 is fed through conductor 58 to a popular desk-top computer 60 equipped with a color monitor, floppy disk drive, hard disk drive, keyboard, and dot matrix printer 62 connected through conductor 64. The software of the computer 60 may be comprised of a plurality of individual, known software packages which are linked by a program, or programs written by the inventors of the present invention to provide the overall result of automatic data handling, record keeping, and record comparison with a minimum of keystrokes on keyboard 66 whereby a person totally uninformed and inexperienced concerning computers or typing can learn to operate these relatively complicated tasks in a matter of hours or possibly in minutes. The software provided by the inventors of the present system also provides for an automatic summary of each boxing session to be printed out through the dot matrix printer which includes the total force applied for the entire training session, number of strikes, force of each strike, average force per strike, average strikes per minute, maximum and minimum force strikes and when such strikes occurred, fastest and slowest time between two hits, and the time when the average force per strike starts to decline rapidly, thereby indicating fatigue of the muscles used to strike the punching bag. Web site: http://www.delphion.com/details?pn=US04941660__ •

Influenza virus subunit conjugates Inventor(s): Harmon; Maurice W. (Tannersville, PA), Huebner; Robert C. (Bartonsville, PA) Assignee(s): Connaught Laboratories, Inc. (Swiftwater, PA) Patent Number: 5,612,037 Date filed: July 26, 1994 Abstract: Conjugates of HA protein of influenza virus suitable for formulation as a vaccine for obtaining a strong immune response to the HA protein are formed by separating whole HA protein from the influenza virus by detergent extraction or by providing whole HA protein by recombinant procedure, treating the HA protein with hydroxylamine to form free sulfhydryl groups in the cytoplasmic domain of the protein,

Patents 153

and cross-linking the free sulfhydryl group-containing HA protein to itself using a bismaleimide linker or to a maleimide-modified diphtheria toxoid, tetanus toxoid or influenza NP protein or other carrier molecule. The procedure is applicable to other proteins which can be separated from a cellular material, such as a virus, and which contain thioester bonds convertible to sulfhydryl groups. Excerpt(s): The present invention relates to conjugation of influenza virus hemagglutinin (HA) to carrier molecules and the use of such conjugates in immunogenic compositions, particularly vaccines for human administration. Whole virus vaccines administered to the body elicit an immune response by the formation of antibodies to the viral antigen. In the case of the influenza virus, it is known that the influenza HA protein is the target of virus neutralizing antibodies for this virus. One commercially-available whole virus vaccine is a split virus vaccine, obtained by treating inactivated virus with detergent, is sold under the trade-mark FLUZONE.RTM. by Connaught Laboratories, Inc. The trend with respect to vaccines is away from whole virus materials and towards more purified materials, which generally are smaller and well defined. The influenza HA antigen has been isolated but the specific subunit materials are only weakly immunogenic and are incapable of inducing a sufficiently high immune response to be effective in many classes of individuals. Web site: http://www.delphion.com/details?pn=US05612037__ •

Means for detecting and analyzing neuroanatomy Inventor(s): Erichsen; Jonathan T. (Stony Brook, NY), Evinger; Craig (Huntington, NY), Karten; Harvey J. (Setauket, NY) Assignee(s): The Research Foundation of State University of New York (Albany, NY) Patent Number: 5,004,683 Date filed: October 6, 1988 Abstract: The present invention is an improved means for detecting neuroanatomical pathways in animals comprising introducing an atoxic fragment C of tetanus toxin into the motor target of a neural circuit, and permitting the atoxic fragment to transport through the neural circuitry. The fragment C of tetanus toxin is then localized along the neuroanatomical pathway by reacting the fragment C with monospecifically reactive antibody produced by a hybridoma cell line selected from the group consisting of.alpha.TTC-17,.alpha.TTC-44,.alpha.TTC-49 and.alpha.TTC-114. The present invention also includes the individual hybridoma cell lines which produce the reactive antibody along with the antibody themselves. Excerpt(s): The present invention relates to the art of neuroanatomy, and, in particular, is directed to an improved means for detecting neural circuits. The present invention has resulted in the course of work conducted with funds provided, in part at least, by an award or grant from the National Institute of Health (NIH). A severe limitation of known neuroanatomical methods known today is that they can only examine the connection between two groups of neurons at one time. Since, however, even simple reflexes result from interactions between three or more neurons, a detailed understanding of the basic neural circuitry is not readily performed by present methods. Accordingly, efforts have been made to provide a neuroanatomical pathway tracer which will cross more than one neuro junction and which can be readily detected. Recent studies on tetanus toxin have demonstrated that this substance moves retrogradely (i.e, backwards) across synaptic junctions, Schwab and Thoenen, "Selective

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Transsynaptic Tetanus Toxin After Retrograde Axonal Transport in Peripheral Symphetic Nerves," BRAIN RESEARCH 122: 459-474 (1977). Thus, this tracer can reveal not just connected pairs of neurons, but also connections between three or more neurons in a single experiment. For example, when tetanus toxin is introduced to neuron A, the tracer moves backwards to neuron B which terminates on neuron A. Then the tracer continues backwards through the nervous system to label the neuron C which, in turn, synapses on neuron B, thereby identifying the neural circuit C-B-A. This feature provides a tremendous tool in determining neuro anatomical circuitry. There are, however, two serious problems regarding the use of tetanus toxin in the nervous system. Tetanus toxin is highly toxic, and the toxin can only be crudely localized by conjugation to I.sup.125, which is highly radioactive. Web site: http://www.delphion.com/details?pn=US05004683__ •

Meningococcal polysaccharide conjugate vaccine Inventor(s): Jennings; Harold J. (Gloucester, CA), Michon; Francis (Ottawa, CA) Assignee(s): National Research Council of Canada (Ottawa, CA) Patent Number: 5,576,002 Date filed: May 5, 1994 Abstract: Neisseria meningitidis group B polysaccharide (GBMP) modified by having sialic acid residue N-acetyl groups replaced by N-acyl groups exhibits enhanced immuno response thereto. In addition, induction of antibodies which cross-react with unmodified group B meningococcal and E. coli K1 capsular polysaccharide and other tissue cells having a common epitope is minimized. Conjugation of the modified polysaccharides with a physiologically acceptable protein such as tetanus toxoid induces the production of specific protective antibodies with negligible levels of GBMPcross reactive antibodies, to thereby afford protection against infections caused by group B meningococci and E. coli K1. Excerpt(s): The present invention is directed to chemically-modified group B polysaccharides of Neisseria meningitidis. The invention also provides vaccines in which the respective modified polysaccharides are conjugated to a protein carrier. Meningitis caused by group B N. meningitidis and E. coli K1 remain major world health problems. Group B meningitis occurs in both endemic and epidemic situations and accounts for approximately half of all recorded cases of meningococcal meningitis, while K1-positive E. coli are the leading cause of meningitis in neonates. Currently there is no vaccine commercially available against disease caused by group B meningococci and E. coli K1. This is in large part due to the fact that the group B meningococcal polysaccharide (GBMP) is only poorly immunogenic in humans. There are some recently reported candidate vaccines based on complexes of the GBMP with outer membrane proteins, but, as yet, there is no clear evidence of their efficacy in humans. Recently, a new concept of a vaccine based on a synthetic chemically modified (Npropionylated) group B polysaccharide-protein (N-Pr-GBMP-protein) conjugate has been developed. The vaccine induces in mice high titers of IgG antibodies which are not only protective, but also cross-react with unmodified GBMP (i.e. N-acetyl-GBMP). This concept is described and claimed in U.S. Pat. No. 4,727,136, issued Feb. 23, 1988 to Harold J. Jennings et al. Web site: http://www.delphion.com/details?pn=US05576002__

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Method and apparatus for improving muscle tone Inventor(s): Kallok; Michael J. (New Brighton, MN) Assignee(s): Medtronic, Inc. (Minneapolis, MN) Patent Number: 5,133,354 Date filed: November 8, 1990 Abstract: An apparatus for and method of improving muscle tone of a patient using chronic sub-tetanic electrical stimulation. For patients suffering from obstructive sleep apnea, for example, the muscles of the upper airway are provided the chronic stimulation to mitigate or prevent the adverse medical condition caused in part by excessively flaccid muscle tissue around and in the airway.A stimulation generator supplies pulses to the muscle to be treated through insulated leads which are coupled to electrodes directly in contact with the appropriate neuro-muscular tissue. The output of the stimulation generator is adjusted to a frequency of sufficiently low level as to prevent fused tetanic contraction of the stimulated muscle. The adjustment may be made manually by attending medical personnel or may be done automatically using electrodes to sense the tension of the stimulated muscle. In the automatic mode, the sensing system insures the stimulation frequency level is decreased below the threshold of muscle tetanus.Stimulation may be accomplished at a particular site or may be mutliplexed to a number of sites. Chronic stimulation will enhance muscle tone to an individual degree and then will simply maintain the desired status. Excerpt(s): The present invention generally relates to implantable medical devices, and more particularly, relates to implantable medical devices which provide non-tetanic stimulation of skeletal muscle tissue. The medical characteristics of sleep apnea have been known for some time. There are two generally recognized forms of the disease. The first is central sleep apnea which is associated with the failure of the body to automatically generate the neuro-muscular stimulation necessary to initiate and control a respiratory cycle at the proper time. Work associated with employing electrical stimulation to treat this condition is discussed in "Diaphragm Pacing: Present Status", by William W. L. Glenn, in Pace, Volume I, at pages 357-370 (Jul.-Sep. 1978). The second condition is known as obstructive sleep apnea. It is discussed at some length in "Obstructive Sleep Apnea: Diagnosis and Treatment", by Drs. Cook and Osguthorpe in Journal of South Carolina Medical Association, 81 (12): 647-651 (Dec. 1985). Additional references treating the subject include: "Physiologic Basis of Therapy for Sleep Apnea", by K. P. Strohl, N.S. Cherniack, and B. Gothe in American Review of Respiratory Disease, Volume 134, pp. 791-802 (1986); and "Obstructive Sleep Apnea Syndrome", by J. Kaplan and B.A. Staats in Mayo Clinic Proceedings, Volume 65, pp. 1087-1094 (1990). Web site: http://www.delphion.com/details?pn=US05133354__

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Method for delivering active agents to mammalian brains in a complex with eicosapentaenoic acid or docosahexaenoic acid-conjugated polycationic carrier Inventor(s): Katz; Robert (Gaithersburg, MD), Tomoaia-Cotisel; Maria (Rockville, MD) Assignee(s): Molecular/Structural BioTechnologies, Inc. (Bethesda, MD) Patent Number: 5,716,614 Date filed: August 5, 1994

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Abstract: A method is disclosed for delivering biologically active agents to a mammalian brain by administering a complex of the biologically active agent with a polycationic carrier coupled to 2-20 eicosapentaenoic acid or docosahexaenoic acid moieties and additional eicosapentaenoic acid or docosahexaenoic acid moieties. The polycationic carrier is poly-lysine, poly-arginine or poly-ornithine of 5-50 amino acid residues. The addition of a targeting moiety selected from tetanus toxin C fragrant,.alpha.bungarotoxin and nerve growth factor to the complex facilitates delivery of the biologically active agent to glial tissue, or to cortical, cholinergic and adrenergic neurons. Excerpt(s): The present invention relates to site-specific biomolecular lipophilic complexes, also called conjugates or transport vectors. These complexes comprise an omega-3 fatty acid and derivatives thereof, and a therapeutic, prophylactic, diagnostic or a research agent. Further, said complex is conjugated with cationic macromolecular carriers to enhance its passage from the blood circulation to the brain. The resultant conjugates are specific for sustained release delivery of said agents to the central nervous system (CNS), particularly to the neurons of the cerebral cortex and corpus striatum (e.g., cholinergic and adrenergic neurons) and to the glial tissue (neuroglial cells, including, astrocytes and macroglial cells) in animals and humans. In addition, targeting moieties such as neurotoxins and fragments thereof are added to said complex to facilitate its uptake by the target brain cells. Also, disclosed are pharmaceutical compositions containing poly-unsaturated site-specific complexes/conjugates for the treatment of a wide variety of diseases relating to severe deterioration of the central nervous system, e.g., dementias, neurodegenerative disorders, neurological diseases, malignant brain tumors, inborn errors of metabolism (i.e., lysosomal storage disorders), and the like. The specification and claims that follow cite numerous patents and publications and their content whether for background or experimental purposes are incorporated by reference herein. Web site: http://www.delphion.com/details?pn=US05716614__ •

Method for production of tetanus toxin using media substantially free of animal products Inventor(s): Demain; Arnold L. (Wellesley, MA), Fang; Aiqi (Somerville, MA) Assignee(s): Massachusetts Institute of Technology (Cambridge, MA) Patent Number: 6,558,926 Date filed: July 16, 1999 Abstract: The present invention provides a system for the growth of C. tetani and production of Tetanus Toxin for use in formulating Tetanus Toxoid preparations. The system includes growth media that contain significantly reduced levels of meat or dairy by-products using non-animal based products to replace the animal-derived products. Preferred media are substantially free of animal-derived products. Excerpt(s): Tetanus is a life-threatening disease caused by infection with Clostridium tetani (C. tetani), a ubiquitous anaerobic spore-forming soil microbe. C. tetani causes disease by releasing a peptide toxin, Tetanus Toxin, that enters the nerve cells of the infected host and blocks release of neurotransmitters at inhibitory synapses. This blockage produces unregulated excitation of certain host neurons, resulting in uncontrollable muscle contraction and paralysis, typically of facial and back muscles. As recently as 1989, 10-40% of C. tetani infections of non-immunized hosts resulted in

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death. For the past 50 years, widespread immunization programs have been in effect to protect against the effects of C. tetani infection. Vaccines are prepared from Tetanus Toxin that has been inactivated, usually by exposure to formalin (Descomby, Can. Roy. Soc. Biol. 91:239, 1924; Plotkin et al., Vaccines, 2nd. Edition, W. B. Saunders, 1994). The inactivated Toxin is known as Tetanus Toxoid. The C. tetani vaccination effort, although it has achieved significant success, has been hampered by certain complications associated with preparation of the Tetanus Toxoid. Because Tetanus Toxin is an extremely potent and dangerous compound (the estimated lethal dose for a human is only 2.5 ng/Kg), it is necessary to inactivate the Toxin very early in its purification process so that the risks of exposure to even partially purified active Toxin is minimized. As mentioned above, Tetanus Toxin is usually inactivated by exposure to formalin, which destroys the activity of the peptide toxin by generating inter-peptide cross-links and adducts. Unfortunately, formalin reactivity is not specific to Tetanus Toxin. A large number of other microbial and media proteins are also cross-linked by formalin. Because the Tetanus Toxin must be treated with formalin at an early stage in its purification, the treatment produces a complex, heterogenous composition containing not only formalin-inactivated Tetanus Toxin, but also formalin adducts of other peptides and proteins that were present in the formalin-treated mixture. Web site: http://www.delphion.com/details?pn=US06558926__ •

Modified meningococcal group B polysaccharide for conjugate vaccine Inventor(s): Gamian; Andrzej (Ottawa, CA), Jennings; Harold J. (Gloucester, CA), Roy; Rene (Gatineau, CA) Assignee(s): Canadian Patents and Development Ltd. (Ottawa, CA) Patent Number: 4,727,136 Date filed: October 1, 1985 Abstract: The group B polysaccharide of Neisseria meningitidis is chemically modified to enhance the immune response thereto, thereby providing cross-reactive antibodies of high affinity. The N-acetyl group of the sialic acid residues of the polysaccharide has been substituted by the N-propionyl group, and this modified antigen then conjugated to a physiologically-acceptable protein such as tetanus toxoid. This conjugate vaccine has been found to raise high titers of high affinity group B IgG antibodies and would be useful against meningitis caused by group B N. meningitidis or by E. coli KI organisms. Excerpt(s): This invention is directed to a vaccine from chemically modified group B polysaccharides of Neisseria meningitidis. The modified polysaccharide is conjugated to a protein carrier to provide the vaccine. Although the groups A, C, Y and W135 capsular polysaccharides of N. meningitidis have been used with some success in providing homologous serogroup immunity in humans, the group B polysaccharide is only poorly immunogenic. The poor immunogenicity of the group B meningococcal polysaccharide (GBMP) and the structurally identical E. coli KI capsular polysaccharide (1, 2, 3) preclude their use as vaccines against meningitis caused by group B meningococcal (GBM) and E. coli KI organisms. Although GBM organisms are able to produce low levels of GBMP-specific antibodies in animals and humans, these antibodies are, with one notable exception, almost exclusively IgM and of relatively low affinity (4). Recently Frosch et al. (5) reported that GBMP-specific monoclonal antibodies of the IgG isotype could be readily produced by injecting a specialized strain of autoimmune NZB mice with GBM organisms. The poor immunogenicity of these polysaccharides is probably attributable to tolerance due to cross-reactive tissue components because of the

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identification of structurally similar.alpha.-(2.fwdarw.8)-linked oligomers of sialic acid in the gangliosides of human and animal fetal brain tissue (6,7). This structural mimicry probably also accounts for the importance of these capsular polysaccharides as virulence factors in the GBM and E. coli KI organisms (3). Because of the poor immunogenicity of the GBMP, other strategies to produce a GBM vaccine have been explored, including the use of serotype protein antigens alone (8) and in combination (9, 10) with the GBMP, and the use of serotype lipooligosaccharides conjugated to protein carriers (11). Web site: http://www.delphion.com/details?pn=US04727136__ •

Multi-component vaccine comprising at least three antigens to protect against disease cased by Haemophilus influenzae Inventor(s): Klein; Michel H. (Willowdale, CA), Loosmore; Sheena M. (Aurora, CA), Yang; Yan-Ping (Willowdale, CA) Assignee(s): Aventis Pasteur Limited (Toronto, CA) Patent Number: 6,342,232 Date filed: March 3, 1999 Abstract: A multi-component immunogenic composition confers protection on an immunized host against infection caused by Haemophilus influenzae. Such composition comprises at least three different antigens of Haemophilus influenzae, two of which are adhesins. High molecular weight (HMW) proteins and Haemophilus influenzae adhesin (Hia) proteins of non-typeable Haemophilus influenzae comprise the adhesin components while the other antigen is a non-proteolytic analog of Hin47 protein. Each component does not impair the immunogenicity of the others. The Haemophilus vaccine may be combined with DTP component vaccines, which may contain inactivated poliovirus, including type 1, type 2 and/or type 3, and/or a conjugate of a capsular polysaccharide of Haemophilus influenzae and tetanus or diphtheria toxoid, including PRP-T, to provide a multi-valent component vaccine without impairment of the immunogenic properties of the other antigens. Excerpt(s): The present invention relates to the field of vaccinology and, in particular, to a multi-component vaccine comprising recombinant proteins from Haemophilus influenzae which is useful in protecting against disease caused by Haemophilus influenzae including otitis media. Haemophilus influenzae is the cause of several serious human diseases such as meningitis, epiglottitis, septicemia and otitis media. There are six serotypes of H. influenzae, designated a to f, that are identified by their capsular polysaccharide. H. influenzae type b (Hib) was a major cause of bacterial meningitis until the introduction of several Hib conjugate vaccines in the 1980's (ref. 1, throughout this application, various references are referred to in parenthesis to more fully describe the state of the art to which this invention pertains Full bibliographic information for each citation is found at the end of the specification immediately preceding the claims. The disclosures of these references are hereby incorporated by reference into the present disclosure). Vaccines based upon H. influenzae type b capsular polysaccharide conjugated to diphtheria toxoid (ref. 2), tetanus toxoid (ref. 3 and U.S. Pat. No. 4,496,538), or Neisseria meningitidis outer membrane protein (ref. 4) have been effective in reducing H. influenzae type b-induced meningitis. The other serotypes of H. influenzae are associated with invasive disease at low frequencies, although there appears to be an increase in the incidence in disease caused by these strains as the incidence of Hib disease declines (refs. 5 and 6). Non-encapsulated or nontypeable H. influenzae (NTHi) are also responsible for a wide range of human

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diseases including otitis media, epiglottitis, pneumonia and tracheobronchitis. The incidence of NTHi-induced disease has not been affected by the introduction of the Hib vaccines (ref. 7). Otitis media is the most common illness of early childhood, with 60 to 70% of all children, of less than 2 years of age, experiencing between one and three ear infections (ref. 8). Chronic otitis media is responsible for hearing, speech and cognitive impairments in children. H. influenzae infections account for about 30% of the cases of acute otitis media and about 60% of chronic otitis media. In the United States alone, treatment of otitis media costs between 1 and 2 billion dollars per year for antibiotics and surgical procedures, such as tonsillectomies, adenoidectomies and insertion of tympanostomy tubes. It is estimated that an additional $30 billion is spent per annum on adjunct therapies, such as speech therapy and special education classes. Furthermore, many of the causative organisms of otitis media are becoming resistant to antibiotic treatment. An effective prophylactic vaccine against otitis media is thus desirable. Web site: http://www.delphion.com/details?pn=US06342232__ •

Noninvasive genetic immunization, expression products therefrom and uses thereof Inventor(s): Curiel; David T. (Birmingham, AL), Marks; Donald H. (Rockaway, NJ), Shi; Zhongkai (Birmingham, AL), Tang; De-chu C. (Birmingham, AL), van Kampen; Kent Rigby (Hoover, AL) Assignee(s): The UAB Research Foundation (Birmingham, AL) Patent Number: 6,348,450 Date filed: May 3, 2000 Abstract: Disclosed and claimed are methods of non-invasive genetic immunization in an animal and/or methods of inducing a systemic immune or therapeutic response in an animal, products therefrom and uses for the methods and products therefrom. The methods can include contacting skin of the animal with a vector in an amount effective to induce the systemic immune or therapeutic response in the animal. The vector can include and express an exogenous nucleic acid molecule encoding an epitope or gene product of interest. The systemic immune response can be to or from the epitope or gene product. The nucleic acid molecule can encode an epitope of interest and/or an antigen of interest and/or a nucleic acid molecule that stimulates and/or modulates an immunological response and/or stimulates and/or modulates expression, e.g., transcription and/or translation, such as transcription and/or translation of an endogenous and/or exogenous nucleic acid molecule; e.g., one or more of influenza hemagglutinin, influenza nuclear protein, tetanus toxin C-fragment, anthrax protective antigen, HIV gp 120, human carcinoembryonic antigen, and/or a therapeutic, an immunomodulatory gene, such as co-stimulatory gene and/or a cytokine gene. The immune response can be induced by the vector expressing the nucleic acid molecule in the animal's cells. The immune response can be against a pathogen or a neoplasm. A prophylactic vaccine or a therapeutic vaccine or an immunological composition can include the vector. Excerpt(s): The present invention relates generally to the fields of immunology and vaccine technology. The present invention also relates to techniques of skin-targeted non-invasive gene delivery to elicit immune responses and uses thereof. The invention further relates to methods of non-invasive genetic immunization in an animal and/or methods of inducing an immunulogical, e.g., systemic immune response or a therapeutic, e.g., a systemic therapeutic response, in an animal, products therefrom and uses for the methods and products therefrom. The invention yet further relates to such

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methods comprising contacting skin of the animal with a vector in an amount effective to induce the response, e.g., systemic immune response, in the animal. Even further, the invention relates to such methods wherein the vector comprises and express an exogenous nucleic acid molecule encoding an epitope or gene product of interest, e.g., an antigen or therapeutic. Still further, the invention relates to such methods wherein the response, e.g., systemic immune or therapeutic response, can be to or from the epitope or gene product. The invention yet further still relates to such methods wherein the nucleic acid molecule can encode an epitope of interest and/or an antigen of interest and/or a nucleic acid molecule that stimulates and/or modulates an immunological response and/or stimulates and/or modulates expression, e.g., transcription and/or translation, such as transcription and/or translation of an endogenous and/or exogenous nucleic acid molecule. The invention additionally relates to such methods wherein the nucleic acid molecule can be exogenous to the vector. The invention also relates to such methods wherein the exogenous nucleic acid molecule encodes one or more of an antigen or portion thereof, e.g., one or more of an epitope of interest from a pathogen, e.g., an epitope, antigen or gene product which modifies allergic response, an epitope antigen or gene product which modifies physiological function, influenza hemagglutinin, influenza nuclear protein, influenza M2, tetanus toxin C-fragment, anthrax protective antigen, anthrax lethal factor, rabies glycoprotein, HBV surface antigen, HIV gp 120, HIV gp 160, human carcinoembryonic antigen, malaria CSP, malaria SSP, malaria MSP, malaria pfg, and mycobacterium tuberculosis HSP; and/or a therapeutic or an immunomodulatory gene, a co-stimulatory gene and/or a cytokine gene. Even further, the invention relates to such methods wherein the immune response can be induced by the vector expressing the nucleic acid molecule in the animal's cells, e.g., epidermal cells. The invention still further relates to such methods wherein the immune response can be against a pathogen or a neoplasm. Web site: http://www.delphion.com/details?pn=US06348450__ •

Nontoxic pseudomonas aeruginosa polysaccharide-toxin a conjugate vaccines

polysaccharide-tetanus

toxoid

and

Inventor(s): Cryz; Stanley J. (Bolligen, CH), Furer; Emil P. (Muri, CH) Assignee(s): Swiss Serum & Vaccine Institute Berne (Berne, CH) Patent Number: 4,771,127 Date filed: August 4, 1986 Abstract: Polysaccharide-protein conjugates were synthesized utilizing polysaccharide derived from hydrolyized Pseudomonas aeruginosa lipopolysacharide covalently coupled to either tetanus toxoid or P. aeruginosa toxin A, utilizing a spacer molecule and a coupling agent. Conjugates produced in such a manner possess a molecular weight of greater than 350,000, are nontoxic and non-pyrogenic, and upon immunization of animals induced protective anti-LPS antibody and antibody which neutralizes the lethal effect of tetanus toxin or toxin A. The polysaccharide-tetanus toxoid conjugate and polysaccharide-toxin A conjugate are safe and immunogenic when parenterally administered to humans. Excerpt(s): Pseudomonas aeruginosa (P. aeruginosa) is a leading cause of lifethreatening nosocomial infections, especially in a compromised host. Human immunity to P. aeruginosa has been correlated with humoral antibody to lipopolysaccharide (LPS) and toxin A, as described in Pollack M. Huang A. I., Prescott R. K., Young L. S., Hunter K. W., Cruess D. F., Tsai C. M., "Enhanced survival in Pseudomonas aeruginosa

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septicemia associated with high levels of circulating antibody to Escherichia coli endotoxin core," J. Clin., Invest. 1983; 72: 1874-1881; Pollack M., Young, L. S., "Protective activity of antibodies to exotoxin A and lipopolysaccharide at the onset of Pseudomonas aeruginosa septicemia in man," J. Clin. Invest. 1979; 63: 276-286; and Cross A. C., Sadoff J. C., Iglewski B. H., Sokol P. A., "Evidence for the role of toxin A in the pathogenesis of infection with Pseudomonas aeruginosa in humans," J. Infect. Dis. 1980; 142: 538-546. Anti-LPS antibody has been shown to be highly protective against P. aeruginosa infections in a variety of animal model systems, as noted in Cryz S. J. Jr., Furer E., Germanier R., "Protection against Pseudomonas aeruginosa infection in a murine burn wound sepsis model by passive transfer of antitoxin A, antilastase, and antilipopolysaccharide," Infect. Immun. 1983; 39: 1072-1079; Cryz S. J. Jr., Furer E., Germanier R., "Passive protection against Pseudomonas aeruginosa infection in an experimental leukopenic mouse model," Infect. Immun. 1983; 40: 659-664; Kazmierowski J. A., Reynolds H. Y., Kauffmann J. C., Durbin W. A., Graw R. G. Jr., Devlin H. B., "Experimental pneumonia due to Pseudomonas aeruginosa in leukopenic dogs: prolongation of survival by combined treatment with passive antibody to Pseudomonas and granulocyte transfusions," J. Infect. Dis. 1977; 135: 438-446; and Pier G. B., Sidberry H. F., Sadoff J. C., "Protective immunity induced in mice by immunization with highmolecular-weight polysaccharide from Pseudomonas aeruginosa," Infect. Immun. 1978; 22: 919-925. However, attempts to use native P. aeruginosa LPS as a vaccine have been hampered by a high frequency of adverse reactions following immunization and the need for numerous injections to evoke an optimal immune response, as noted in Alexander T. W., Fisher M., "Immunization against Pseudomonas infection after thermal injury," J. Infect. Dis. 1974; 130 (Suppl.): 152-158; Haghbin M., Armstrong D., Murphy M. L., "Controlled prospective trial of Pseudomonas aeruginosa vaccine in children with acute leukemia," Cancer 1973; 32: 761-766; and Young L. S., Meyer R. D., Armstrong D., "Pseudomonas aeruginosa vaccine in cancer patients," Annals Int. Med. 1973; 79: 518527. As described in Liu P.V., "Extracellular toxins of P. aeruginosa," J. Infect. Dis. 130 (Suppl.): 594-599 1974, toxin A is the most toxic product, on a weight basis, synthesized by P. aeruginosa. Toxin A acts to inhibit eucaryotic protein synthesis by catalyzing the transfer of the adenosine diphosphate-ribosyl (ADPR) moiety of nicotinamide adenine dinucleotide onto eucaryotic elongation factor 2, as discussed in Iglewski, B.H., Liu, P.V. and Kabat, D., "Mechanism of Action of P. aeruginosa exotoxin A: ADP-ribosylation of mammalian elongation factor 2 in vitro and in vivo," Infect. Immun. 15: 138-144, 1977 and Ohman, D.E., Burns R.P. and Iglewski B.H., "Corneal Infections in mice with toxin A and elastase mutants of P. aeruginosa," J. Infect. Dis. 142: 547-555, 1980. Antitoxin A antibody either passively administered or induced by active vaccination with a toxin A toxoid has provided significant protection against experimental P. aeruginosa infection. Additional investigations have demonstrated a direct correlation between antitoxic antibody and survival of patients from an episode of P. aeruginosa bacteremia, as described in Cross, A.S., Sadoff, J.C., Iglewski, B.H., and Sokol, P.A., "Evidence for the role of toxin A in the pathogenesis of human infection with Pseudomonas," J. Infect. Dis. 142: 538-46, 1980 and Pollack M.S. and Young, L.S., "Protective activity of antibodies to exotoxin A and lipopolysaccharides at the outset of P. aeruginosa septicemia in man," J. Clin. Invest. 63: 276-86, 1979. Web site: http://www.delphion.com/details?pn=US04771127__

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Novel substance M-9337 and process for preparing same Inventor(s): Miyamura; Sadao (Niigata, JP) Assignee(s): SS Pharmaceutical Co., Ltd. (Tokyo, JP) Patent Number: 4,334,025 Date filed: January 30, 1981 Abstract: Novel substance M-9337 obtained by culturing Streptomyces antihaemolyticus is effective as an antitoxic substance for neutralizing toxins discharged from streptococci, staphylococci, tetanus or the like. Excerpt(s): This invention relates to novel substance M-9337 and a process for preparing same. Toxins discharged from streptococci, staphylococci, tetanus and the like cause a hemolytic reaction and bring about various diseases. The present inventor has made extensive studies to find out an antitoxic substance for neutralizing these toxins and, as a result, found that a novel strain belonging to the genus Streptomyces which has been isolated by the present inventor is able to produce a novel substance M-9337 capable of inhibiting the hemolytic reaction. The present invention is accomplished on the basis of the above finding. The strain capable of producing the substance M-9337 according to the invention has the following mycological properties. Web site: http://www.delphion.com/details?pn=US04334025__

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Peptide which produces protective immunity against tetanus Inventor(s): Halpern; Jane L. (Washington, DC) Assignee(s): The United States of America as represented by the Department of Health (Washington, DC) Patent Number: 5,601,826 Date filed: April 20, 1994 Abstract: The invention provides an immunogen against tetanus toxin including a peptide having a single, linear, antigenic, tetanus-toxin-specific epitope. The epitope is derived from the heavy chain C fragment of the toxin. In a preferred embodiment, the immunogen includes the last 20 amino acids of the toxin, including the carboxy terminus. Antibodies, including antipeptide antibodies, are also provided as well as methods of vaccination. Excerpt(s): Tetanus is an acute infectious disease caused by the anaerobic bacteria Clostridium tetani. A potent protein neurotoxin elaborated by the bacteria causes the manifestations of the disease. Typically, tetanus is characterized by neurological symptoms including convulsions and intermittent muscle spasms. Lockjaw is a common name for the disease. The neurotoxin inhibits neurotransmitter release by an undetermined mechanism of action believed to require at least three steps: 1) binding to a eukaryotic cell receptor, 2) translocation to the cytosol and 3) disruption of the secretory pathway. The precise structure of the receptor for tetanus toxin has not been identified. Tetanus toxin binds to certain gangliosides present on neuronal cells, and some studies indicate that these gangliosides may act as the cellular receptor for tetanus toxin. It has also been proposed that tetanus toxin must interact with gangliosides plus an additional receptor in order for intoxication to proceed. A vaccine based on the tetanus toxin, referred to as tetanus toxoid, causes the individual to produce antitoxin antibodies and thus provides active immunity. Survival of the patient after an active

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injection of tetanus does not cause immunity to further episodes of tetanus because the amount of neurotoxin sufficient to cause the disease is less than the amount of neurotoxin necessary to produce active immunity. Web site: http://www.delphion.com/details?pn=US05601826__ •

Peripheral nerve stimulator Inventor(s): Kaldun; Mark R. (St. Paul, MN), Miller; Curtis H. (Burnsville, MN) Assignee(s): Med General, Inc. (Minneapolis, MN) Patent Number: 4,157,087 Date filed: March 6, 1978 Abstract: An electronic peripheral nerve stimulator which may be used to monitor the type of neuromuscular blocks present in a patient following the administration of a muscle relaxant drug. An integrated circuit monostable multivibrator or one-shot is coupled to an amplifier and output stage. Plural integrated astable multivibrators are provided which may be selectively employed to trigger the one-shot circuit to thereby produce stimulating impulses of several predetermined repetition rates and duty cycles useful for producing the so-called "twitch" and "tetanus" responses of a patient's digital members. The peripheral nerve stimulator also includes indicating means for the poweron condition of the unit as well as for a low battery charged condition. Excerpt(s): This invention relates generally to an electronic nerve stimulating device and more particularly to the improved design of a peripheral nerve stimulator useful in monitoring the nature of neurological blocks present in a patient following the administration of muscle relaxant drugs to the patient. As is disclosed in the Ide et al U.S. Pat. No. 3,364,929, prior to surgery it is a common practice to administer muscle relaxant drugs such as succinylcholine and dimethyl tubocurare to the patient. Such drugs are found to produce depolarization or non-depolarization types of neuromuscular blocks in patients. Oftentimes, following surgery, it is desired that an antagonist drug be administered to counteract the effects of the muscle relaxant drug previously administered. It is also known that the antagonist drug should be introduced into the patient only when a non-depolarizing block exists in that the introduction of an antagonist drug when a depolarizing block is present is found to potentiate the depolarizing block rather than counteracting the muscle relaxant drug. As is further set out in the Ide et al U.S. Pat. No. 3,364,929 and the Ide U.S. Pat. No. 3,565,080, the type of block extant within the patient, i.e., depolarizing or non-depolarizing, can be determined by applying electrical stimulation to a peripheral member of the body of the patient and noting the effect of that stimulation on the patient's digits. For example, if electrical pulses of a relatively low repetition rate are applied to the ulnar nerve, a characteristic twitch may be observed in the fingers of the patient. If a stimulation signal of a higher repetition rate is applied to the ulnar nerve, the fingers exhibit a constant contraction called tetanus. If, following the application of the relatively high frequency stimulating pulses, the relatively low frequency pulses are again applied, two different types of twitch reaction take place depending upon whether the patient is exhibiting a non-depolarizing block or a depolarizing block. Web site: http://www.delphion.com/details?pn=US04157087__

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Polysaccharide-protein conjugates Inventor(s): Robbins; John B. (Chevy Chase, MD), Schneerson; Rachel (Bethesda, MD), Szu; Shousun C. (Bethesda, MD) Assignee(s): The United States of America as represented by the Department of Health (Washington, DC) Patent Number: 5,204,098 Date filed: February 16, 1988 Abstract: Vi capsular polysaccharides conjugated to toxin-dependent proteins can be used to enhance antibody response and to convert T-dependent properties to the Vi capsular polysaccharide. A heterobifunctional crosslinking agent can be used to bind thiol derivatives of the Vi capsular polysaccharides to the proteins, such as diphtheria, tetanus toxoids, cholera toxin and Haemophilus influenzae. Excerpt(s): The present invention relates to immunoprophylaxis and vaccines; more particularly it relates to Vi capsular polysaccharide-protein conjugates which can be used to elicit immune response by producing serum antibodies in a host. Enteric fevers continue to cause considerable morbidity and mortality in countries that have not yet achieved control of sewage disposal and contamination of drinking water. In these countries, the most frequent and serious cause of enteric fevers is Salmonella typhi (typhoid fever). Immunoprophylaxis against typhoid fever on a world-wide basis has not been attempted because the two presently available vaccines have limitations. The cellular typhoid vaccines induce only a limited immunity and elicit side reactions that are sufficiently frequent and sever to have discouraged their widespread acceptance. An orally administered attenuated strain of S. typhi., Ty-21a, requires three to four doses to induce about 65% protection. This vaccine is expensive, and its mode of protection has not been identified, which has prevented precise standardization of the vaccine. Recently, two clinical evaluations, in populations with high rates of typhoid fever (about 1%/annum), have provided evidence that immunization with the capsular polysaccharide of S. typhi. (Vi) confers immunity against typhoid fever, cf. Klugman et al., Abstract 27th ICAAC, New York, N.Y., 1987; and Acharya et al., Prevention of typhoid fever in Nepal with the Vi capsular polysaccharide of Salmonella typhi, in press, 1987. The Vi vaccine, prepared under conditions which did not change its structure, elicited a four-fold or greater rise in serum antibodies in about 75% of children and adults in Nepal and in school children in the Eastern Transvaal, Republic of South Africa. The protective efficacy of the Vi in these two trials was about 70%. In contrast, the same Vi elicited a.gtoreq.four-fold antibody rise in 97% of young adults in Q France and the United States. The seroconversion rate and efficacy of other capsular polysaccharides, e.g., meningococcal vaccines, were also lower in Africa than in Finland or the United States. This lesser immunogenicity and efficacy of meningococcal vaccines was attributed to the high burden of infections, including malaria, in the African population. Since the protective response elicited by capsular polysaccharide vaccines is serum antibodies, it could be predicted that a more immunogenic Vi would be more protective against typhoid fever in high-risk populations. Web site: http://www.delphion.com/details?pn=US05204098__

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Previns as specific inhibitors and therapeutic agents for Botulinum toxin B and Tetanus neurotoxins Inventor(s): Doctor; Bhupendra P. (Potomac, MD), Garcia; Gregory E. (Germantown, MD), Gordon; Richard K. (Potomac, MD), Moorad; Debbie R. (Rockville, MD) Assignee(s): The United States of America as represented by the Secretary of the Army (Washington, DC) Patent Number: 6,573,244 Date filed: May 12, 2000 Abstract: The compounds of the invention are generally described by the formula:B.sub.1 Z*.sub.2 B.sub.3 Z*.sub.4 X*.sub.5 Q.sub.6 F.sub.7 X.sub.8 X.sub.9 X.sub.10 X.sub.11 (1),B.sub.1 X.sub.2 X.sub.3 X.sub.4 X.sub.5 Q.sub.6 F.sub.7 X.sub.8 X.sub.9 X.sub.10 X.sub.11 (2),orB.sub.1 X.sub.2 B.sub.3 X.sub.4 Z.sub.5 Q.sub.6 F.sub.7 Z*.sub.8 X.sub.9 X.sub.10 X.sub.11 (3)and the salts, esters, amides, and acyl forms thereof. Each position represented by a letter indicates a single amino acid residue: B is a basic or polar/large amino acid or a modified form thereof; X is a small or hydrophobic amino acid or a modified form thereof; X* is a small or polar/large amino acid or a modified form thereof; Z is a polar/large or hydrophobic amino acid or a modified form thereof; Z* is Proline or a polar/large or hydrophobic amino acid or a modified form thereof. As described below, one or more of the peptide linkages between the amino acid residues may be replaced by a peptide linkage mimic.These compounds may be used as molecular building blocks to create compounds that are optimized for inhibiting the protease activity of Botulinum B and tetanus toxins. Excerpt(s): The invention relates to a class of peptide and peptide-like compounds, "Previns" which inhibit the enzymatic activity of Botulinum toxin B and Tetanus neurotoxins and may be used as molecular building blocks for creating compounds which are optimized for inhibiting the protease activity of Botulinum toxin B and Tetanus neurotoxins. The Botulinum toxins (Bttxs) are among the most potent toxins to animals, e. g. the LD.sub.50 in mice is about 1 ng/kg. Bttxs comprise a family of seven distinct serotypes (A-G). Bttxs are composed of two subunits comprising a 100 kdal nerve-cell targeting heavy chain and a 50 kdal endoproteolytically active light chain. These toxins are Zn-metalloproteases and contain a Zn-protein binding motif HEXXH. However, Zn-metalloprotease inhibitors, such as angiotensin converting enzyme inhibitors, captopril and phosphoramidon, are not effective inhibitors of Bttxs. Although Zn-chelators inhibit Bttx protease activity in vitro, they merely delay the protease activity in vivo and in tissue preparations comprising intact nerve and muscles cells and/or tissues. Furthermore, some Zn-chelators are toxic at concentrations necessary to delay the Bttx protease activity. Although dithiocarbamates inhibit other Zn-containing proteins such as SOD, they are ineffective against the Bttx serotype B (BttxB). Clearly, inhibitors of the various Bttx serotypes, such as BttxB, are needed. Web site: http://www.delphion.com/details?pn=US06573244__

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Process for the preparation of lyophilized, adsorbed polyvalent vaccines Inventor(s): Bacskai; Laszlo (Budapest, HU), Csizer; Zoltan (Budapest, HU), Joo; Istvan (Budapest, HU), Niedermayer; Eleonora (Budapest, HU), Rethy; Lajos (Budapest, HU), Sikos; Karoly (Budapest, HU), Zsidai; Jozsef (Budapest, HU) Assignee(s): Human Oltoanyagtermelo Es Kutato Intezet (Budapest, HU) Patent Number: 4,578,270 Date filed: February 22, 1984 Abstract: The invention relates to the preparation of lyophilized, absorbed polyvalent vaccines. According to the invention tetanus, diphtheria, pertussis and optionally typhus antigens concentrated to 5 to 15 doses/3 ml are adsorbed at a pH value of 3 to 6 to an insoluble carrier concentrated in the same way as the antigens, then the pH of the mixture is adjusted to a value of 5 to 6 and lyophilized together with a protective material commonly used in lyophilizing processes. Before administration the lyophilized vaccine is diluted to the concentration required by a physiological saline buffered to a pH value of 6.8 to 7 by a phosphate solution. Excerpt(s): This invention relates to the preparation lyophilized, adsorbed polyvalent vaccines. The polvalent vaccines, e.g. the diphtheria-tetanus-pertussis (in the following: Di-Te-Pe) vaccine, play an important role in the extended vaccination program of the World Health Organization (WHO). The aim of this program is to prevent the most dangerous infectious diseases of childhood by vaccination. However, the effectivity of the vaccines commercially available at present is diminished during storage. Particularly under tropic conditions, these Di-Te-Pe vaccines can only be stored for a very short time period; as a consequence of the heat sensitivity of the pertussis component these are only stable for about 1 to 2 weeks. During the past years, the inventors have studied the stability of the pertussis and Di-Te-Pe vaccines in detail [Csizer Z., Joo I., Zsidai J., Hegedus L.: J. Biol. Standard 1, 347 (1973); Csizer Z., Zsidai J., Joo I.: Atca Microbiol. Acad. Sci. Hung. 22, 83 (1975); Csizer Z., Zsidai J., Joo I.: Acta Microbiol. Acad. Sci. Hung. 25, 1 (1978)] and carried out 400 active immunization experiments on mice by using 53 pertussis strain suspension mixtures within the period from 1960 to 1973. It was determined by the statistical analysis of these investigations that, when stored at 5.degree. to 10.degree. C., the activity of the suspensions decreased after 8 years below the value of 4 international units (IU) which is a single human dose for immunization. From 1968 to 1974, 207 active immunization experiments were carried out by using 21 Di-Te-Pe vaccines on mice. It could be stated from the statistical analysis of the results that, when stored at 5.degree. to 10.degree. C., the activity after 6 years of the pertussis component meets the international and domestic requirements [WHO Techn. Rep. Ser. 638, 37 (1979); Hungarian Pharmacopoeia VI. (1967)]. The mean decrease per one year in the activity of the pertussis strain suspension mixtures is 1.01 IU, while that of the pertussis component of the Di-Te-Pe vaccines is 0.35 IU. Thus, a storage at 5.degree. to 10.degree. C. is suitable to maintain the activity. When stored at 37.degree. C., the activity of the vaccines significantly diminishes within 2 weeks, and even this storage temperature is also difficult to assure under tropical conditions. Web site: http://www.delphion.com/details?pn=US04578270__

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Process for the preparation of tetanus toxoid vaccine Inventor(s): Knight; Peter Anthony (Beckenham, GB), Sheppard; Anthony James (Beckenham, GB) Assignee(s): Medeva Pharma Limited (Surrey, GB) Patent Number: 6,060,067 Date filed: March 1, 1995 Abstract: A process for the preparation of tetanus toxoid, which process comprises incubating purified tetanus toxin with 0.2 to 1% (v/v) formaldehyde in the presence of 0.005 to 0.25M lysine for from 24 to 32 days at a pH of from 6.0 to 8.0 and a temperature of from 30 to 45.degree. C. Excerpt(s): This invention relates to a process for the preparation of tetanus toxin for use in tetanus vaccines. The existing tetanus vaccine is produced from a 7-day bottle culture of Clostridium tetani which is inactivated ("toxoided") by the addition of formaldehyde. The formaldehyde is added as formalin. Toxoid is purified for use in a vaccine by salt fractionation to a specific activity of approximately 1200 flocculation units (Limes flocculationis, Lf)/mg protein nitrogen (PN), which is equivalent to 30% to 40% purity. Attempts have been made to increase the specific activity of the vaccine by purifying the toxoid using immunoadsorbents (Hughes et al, J. Appl. Bact. 37, 603-621, 1974). This however only resulted in a limited increase, to 1600 Lf/mg PN. GB-A-969772 discloses a method for producing a toxoid from a purified bacterial toxin, especially purified diphtheria toxin, by treating the toxin in an aqueous medium with formaldehyde in the presence of an aliphatic diamine of molecular weight below 200 which contains a primary or secondary amino group. Preferred diamines are lysine and ethylenediamine. Web site: http://www.delphion.com/details?pn=US06060067__

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Recombinant DNAS encoding three-part hybrid proteins Inventor(s): Murphy; John R. (Wayland, MA) Assignee(s): Seragen, Inc. (Hopkinton, MA) Patent Number: 5,965,406 Date filed: June 7, 1995 Abstract: Disclosed is a recombinant DNA molecule encoding a hybrid protein comprising a first part, a second part, and a third part,(a) wherein said first part comprises a portion of the binding domain of a cell-binding polypeptide ligand effective to cause said hybrid protein to bind to a cell of an animal;(b) wherein said second part comprises a portion of a translocation domain of naturally occurring protein selected from the group consisting of diphtheria toxin, botulinum neurotoxin, ricin, cholera toxin, LT toxin, C3 toxin, Shiga toxin, Shiga-like toxin, pertussis toxin and tetanus toxin, which translocates said third part across the cytoplasmic membrane into the cytosol of the cell; and(c) wherein said third part comprises a polypeptide entity to be introduced into the cell, wherein said third part is non-native with respect to said naturally occurring protein of (b). Excerpt(s): This invention relates to hybrid molecules having a cell-binding part and a translocation part. The literature contains many examples of fused genes which code for hybrid proteins. For example, Villa-Komaroff et al., Proc. Natl. Acad. Sci. U.S.A. 75: 3727-3731, 1978, describes a fused gene made up of a eukaryotic structural gene fused to

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a non-cytoplasmic bacterial gene. The fused gene codes for a hybrid protein which is transported out of the cytoplasm. Hybrid proteins also have been made by other methods (e.g., the coupling of two different protein molecules) which do not involve recombinant DNA techniques. For example, it has been proposed to form, by coupling, therapeutic hybrid proteins consisting of portions of toxin molecules coupled to a ligand capable of binding specifically to a selected class of cells. One attempt to make such a hybrid protein, reported in Chang et al., J. Biol. Chem. 252:1515-1522, 1977, resulted in a hybrid consisting of the diphtheria toxin A chain coupled to human placental lactogen hormone by cross-linking through a disulfide bond. The hybrid protein, although it bound to cells containing lactogen receptors, did not inhibit protein synthesis in those cells. Web site: http://www.delphion.com/details?pn=US05965406__ •

Superoxide dismutase/tetanus toxin fragment C hybrid protein Inventor(s): Brown; Robert H. (Needham, MA), Fishman; Paul S. (Baltimore, MD), Francis; Jonathan W. (Mansfield, MA), Hosler; Betsy A. (Melrose, MA) Assignee(s): The General Hospital Corp. (Boston, MA), University of Maryland at Baltimore (Baltimore, MD) Patent Number: 5,780,024 Date filed: June 21, 1996 Abstract: Disclosed is a 68 kD recombinant hybrid protein comprising an enzymatically active Cu/Zn superoxide dismutase ("SOD-1") moiety and a tetanus toxin fragment C ("TTC") moiety, wherein the TTC moiety selectively delivers the hybrid protein into neurons, and the SOD-1 moiety retains substantial enzymatic activity, following neuronal uptake. Also disclosed are a DNA expression vector encoding the hybrid protein. Excerpt(s): This application claims benefit from provisional application Ser. No. 60/000,473, filed Jun. 23, 1995, and is a continuation-in-part of application Ser. No. 60/000,473. Oxidative stress (or oxidative damage) has been implicated in various neurological diseases and disorders, including stroke, brain hypoxia-reperfusion, trauma, epilepsy, and age related degenerative disorders of the brain, such as Parkinson's disease, Huntington's disease, and amyotrophic lateral sclerosis (Coyle, J. T. et al., (1993) Science 262, 689-695; Olanow, C. W. (1993) Trends Neurosci. 16, 439-444). Oxidative stress is largely a matter of cellular damage caused by oxygen-derived free radicals, i.e., superoxide radicals and hydroxyl radicals. An important biological mechanism for coping with oxygen-derived free radicals is the activity of superoxide dismutase enzymes, which "scavenge" superoxide radicals (by dismutating them to form hydrogen peroxide, which is eliminated by catalase). Cu/Zn superoxide dismutase ("SOD-1") is a 32 kD homodimeric enzyme. Mutations in human SOD-1 have been associated with the inherited form of amyotrophic lateral sclerosis ("FALS") (Rosen et al. (1993) Nature 362: 59-62). The therapeutic use of SOD-1 presents at least two practical difficulties. First, human SOD-1 is an intracellular, cytosolic enzyme with an isoelectric point of 4.5, and it does not readily cross cell membranes (Michelson et al. (1980) Acta Physiol. Scand. 492 (Suppl): 67-80). Second, the molecular weight of SOD-1 is well below the renal glomerular filtration cutoff. This results in rapid clearance of exogenous SOD-1 from the circulation (Inoue et al. (1990) in Antioxidants in Therapy and Preventive Medicine (Emerit et al., eds), pp. 5-12, Plenum Press, New York). In efforts to overcome these limitations, SOD-1 has been entrapped in liposomes (Turrens (1984) J. Clin. Invest.

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73: 87-95); conjugated to albumin (Takeda et al. (1993) Am. J. Physiol. 264: H1708H1715); conjugated to polyethylene glycol (Beckman et al. (1988) J. Biol. Chem. 263: 6884-6892); and expressed as a fusion protein comprising a heparin-binding peptide (Inoue et al. (1991) J. Biol. Chem. 266: 16409-16414). Web site: http://www.delphion.com/details?pn=US05780024__ •

Synthetic peptides useful as universal carriers for the preparation of immunogenic conjugates and their use in the development of synthetic vaccines Inventor(s): Bianchi; Elisabetta (Rome, IT), Corradin; Giampietro (Lausanne, CH), Pessi; Antonello (Rome, IT) Assignee(s): Eniricerche S.p.A. (Milan, IT) Patent Number: 5,196,512 Date filed: November 8, 1990 Abstract: The synthetic peptide TT3, the amino acid sequence of which corresponds to the region 947-967 of the tetanus toxin is recognized by different human Th cell clones in association with a wide range of alleles of the human major histocompatibility complex (MHC). Said peptide contains at least two epitopes, of which one (953-967) is recognized by the DR5-restricted clones and the other (947-960) is recognized by all other DR and DP alleles restricted clones. The TT3 peptide and the peptide corresponding to the 947-960 epitope can be used as universal carriers in the preparation of immunogenic conjugates consisting of at least one of said peptides and a natural or synthetic hapten derived from a pathogenic agent of interest.The immunogenic conjugates are particularly suitable for preparing synthetic vaccines able to provide a protective immunity against different pathogenic agents which is not genetically restricted or is only slightly genetically restricted. Excerpt(s): This invention relates generally to immunogenic conjugates consisting of a universal peptide carrier covalently bound to a hapten derived from a pathogenic agent of interest and their use in the development of synthetic vaccines. In particular, the present invention relates to synthetic peptides having the amino acid sequence corresponding respectively to the amino acid residues 947-967 and 947-960 of the tetanus toxin useful as universal carriers in the preparation of immunogenic conjugates. The invention also relates to the use of said immunogenic conjugates in the development of vaccines able to induce protective immunity against different pathogenic agents which is not genetically restricted or only slightly so. The term "hapten" signifies a molecule able to bind to specific antibodies (antigenic) but not to induce antibody formation or to induce it to only a low antibody count (not immunogenic). Web site: http://www.delphion.com/details?pn=US05196512__

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Tetanus toxin functional fragment antigen and tetanus vaccine Inventor(s): Matsuda; Morihiro (Suita, JP) Assignee(s): The Research Foundation of Microbial Diseases of Osaka University (Osaka, JP) Patent Number: 6,372,225 Date filed: September 24, 1997 Abstract: Disclosed is a tetanus toxin functional fragment antigen (FFA), comprising at least one fragment which is substantially the same as that obtained by a process comprising the steps of splitting at least one peptide bond selected from peptide bonds individually connecting mutually adjacent amino acid residues in a partial amino acid sequence between two cysteine residues participating in forming a disulfide bridge present in the N-terminal of the entire amino acid sequence of the whole tetanus toxin molecule, splitting the disulfide bridge, and splitting non-covalent bonds between groups on the tetanus toxin molecule; wherein the tetanus toxin FFA has a molecular weight of from 90,000 to 110,000 as measured by an SDS-polyacrylamide gel electrophoresis method, and an isoelectric point of 7.25.+-.0.5 as measured by an isoelectric focusing method. The FFA of the present invention not only has a satisfactory immunopotency as a tetanus vaccine antigen, that is, has an immunopotency which is substantially the same as that of a whole tetanus toxin toxoid, but is also extremely excellent with respect to the diminution of adverse side effects. Further, the present invention provides a method for mass production of the FFA, and a tetanus vaccine comprising the FFA, and a combined vaccine comprising the tetanus vaccine and at least one vaccine other than the tetanus vaccine. Excerpt(s): The present invention relates to a tetanus toxin functional fragment antigen and a tetanus vaccine comprising the same. More particularly, the present invention is concerned with a specific tetanus toxin functional fragment antigen which is extremely useful as an antigen for a tetanus vaccine since the functional fragment antigen is advantageous not only in that it is extremely excellent with respect to the diminution of side effects when used as an antigen, as compared to the current tetanus vaccine comprising as an antigen a whole tetanus toxin toxoid, but also in that it has an immunopotency which is substantially the same as that of the whole tetanus toxin toxoid. The present invention is also concerned with a very safe and effective tetanus vaccine (tetanus toxoid) comprising the tetanus toxin functional fragment antigen as an active component, a combined vaccine comprising the tetanus vaccine and at least one vaccine other than the tetanus vaccine, and methods for producing the fragment antigen and vaccines. As is well known, tetanus is an infectious disease with extremely high mortality which produces serious symptoms, such as opisthotonos and dyspnea. Tetanus bacilli are widely distributed in the environments, and their spores are commonly found in soil, feces of animals, and the like. Therefore, every individual is exposed to the danger of tetanus infection from various types of traumas, such as punctured wounds and crushed wounds. Moreover, when an individual is infected with tetanus bacilli, conventional chemotherapies using antibiotics, muscle relaxants and the like cannot grossly change the mortality, whether tetanus patients are elderly or young. In developed countries, most deaths from tetanus have recently occurred among the elderly patients who escaped from vaccination against tetanus in their babyhood. Further, even when an individual receives tetanus vaccination in baby- or child-hood for basal immunization and receives a booster, the immunity remaining in adulthood is not sufficient for preventing tetanus infection when the individual suffers unexpected injury in earthquakes, fires, traffic accidents or the like. Therefore, it is important for

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adults of the ages above ca. 40, especially elderly persons, to receive personally a booster injection in order to ensure protection against tetanus. Web site: http://www.delphion.com/details?pn=US06372225__ •

Thiolated polypeptide compound derived from a tetanus toxin fragment, the process for obtaining and its application Inventor(s): Bizzini; Bernard (Paris, FR) Assignee(s): Institut Pasteur (Paris, FR) Patent Number: 4,594,336 Date filed: April 19, 1984 Abstract: The present invention relates to a new thiolated polypeptide compound derived from a fragment of tetanus toxin.This thiolated polypeptide compound is constituted by the B-II.sub.b fragment of tetanus toxin to which at least one --SH group is directly or indirectly bound.Application: neuropharmacological retrograde axonal transport agent for transporting a medicine to the central nervous system. Excerpt(s): The present invention relates to a new thiolated polypeptide compound derived from a fragment of tetanus toxin, the process for obtaining this compound and the application of the latter, in particular as a neuropharmacological transport agent and as a specific labelling agent of neuronal cells. This hapten-carrier conjugate is used as reagent in an immunochemical process and also for immunization of an animal in order to obtain corresponding antibodies [see on page 4, lines 20 to 32]. The tetanus toxoid is therefore used as a carrier of the hapten in the body of the animal for obtaining antibodies. However, there exists no teaching in this FR patent about a particular fragment of tetanus toxin and its possible use as axonal transport agent for drugs. Web site: http://www.delphion.com/details?pn=US04594336__

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Toxin assay Inventor(s): Hallis; Bassam (Salisbury, GB), James; Benjamin Arthur Frederick (Salisbury, GB), Quinn; Conrad Padraig (Salisbury, GB), Shone; Clifford Charles (Salisbury, GB) Assignee(s): Microbiological Research Authority (Salisbury, GB) Patent Number: 5,962,637 Date filed: December 3, 1996 Abstract: A toxin assay that uses a substrate for cleavage by the toxin and antibodies that do not recognise the substrate but recognise and bind to the product of cleavage of the substrate by the toxin. The substrate can be a nerve cell peptide when the assay is for botulinum toxin or tetanus toxin. Excerpt(s): The invention is in the field of antibody-based assays for toxins having peptidase activity. In particular, this invention relates to assays for toxins, in particular botulinum neurotoxins and tetanus toxins. The invention also relates to antibodies useful in the assays and to peptides immobilized on solid phase supports that are useful in the assays. The botulinum neurotoxins are a family of structurally similar, but antigenically different protein neurotoxins which act on the peripheral nervous system

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to block neuromuscular transmission. These neurotoxins are extremely potent, with a human lethal dose in the order of micrograms, and give rise to the rare but frequently fatal disease, botulism. Assays for the botulinum neurotoxins are currently used in both the food and pharmaceutical industry. The food industry employs assays for the botulinum neurotoxins to validate new food packaging methods and to ensure food safety. With the growing clinical use of the botulinum toxins, the pharmaceutical industry requires accurate assays for these toxins for both product formulation and quality control. It is known to assay for botulinum toxin in foodstuffs using the mouse lethality test. This test has been the industry standard for many years, though over the past 10 years a number of immunoassay methods have been developed in an attempt to replace the mouse test in the majority of applications. Web site: http://www.delphion.com/details?pn=US05962637__ •

Vaccine composition comprising autologous epidermal growth factor or a fragment or a derivative thereof having anti-tumor activity and use thereof in the therapy of malignant diseases Inventor(s): Davila; Augustin Bienvenido Lage (Habana, CU), Delgado; Irene Beausoleil (Habana, CU), Gandolf; Gilda Nurez (Habana, CU), Marinello; Gisela Gonzalez (Habana, CU), Peztana; Eduardo Suarez (Habana, CU), Ramirez; Belinda Sanchez (Habana, CU) Assignee(s): Centro De Immunologia Molecular (Havana, CU) Patent Number: 5,894,018 Date filed: February 21, 1996 Abstract: The invention provides novel uses of EGF and vaccine compositions comprising EGF. In particular, autologous EGF, or a fragment or a derivative thereof, is used as an active immunization against the proliferation of EGF-dependent tumors, or other EGF-dependent diseases. Autologous EGF is preferably coupled to a carrier protein, such as tetanus toxoid or Cholera toxin B chain. The vaccine compositions according to the invention will usually comprise an adjuvant such as aluminum hydroxide. Excerpt(s): This invention relates to the field of immunology, in particular to vaccine compositions able to produce an autoimmune reaction against autologous (self) Epidermal Growth Factor (EGF). An important object of this invention is to obtain a vaccine composition for the active immunotherapy of EGF dependent malignant tumors (e.g. epidermoid carcinoma of lung, glioblastoma multiforme and head and neck epidermoid carcinomas), which can inhibit the proliferation of those tumors, and which therefore are useful for the treatment of malignant neoplasms and of other EGF related diseases. Thus, the invention is also related to the field of cancer therapy. Epidermal Growth Factor, a polypeptide that stimulates epithelial cell proliferation, has been considered to be one of the growth factors involved in malignant transformations. Its action is mainly performed via its membrane receptors. Web site: http://www.delphion.com/details?pn=US05894018__

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Vaccine composition containing polyribosylribitol phosphate and method for making same Inventor(s): Arminjon; Francois (Lyons, FR), Cartier; Jean-Rene (Lyons, FR) Assignee(s): Pasteur Merieux Serums, et Vaccins S.A. (Lyons, FR) Patent Number: 6,333,036 Date filed: December 30, 1997 Abstract: Vaccine compositions are disclosed which comprise at least one antigen formed by the capsular polysaccharide of Haemophilus influenzae type b or high molecular weight polyribosylribitol phosphate coupled to tetanus anatoxin. Excerpt(s): The invention relates to the field of vaccine compositions and more particularly to vaccine compositions comprising at least one antigen formed by the capsular polysaccharide of Haemophilus influenzae type b or high molecular weight polyribosylribitol phosphate coupled to tetanus anatoxin. An antigen which can be used for vaccine purposes in man in order to protect him from infections caused by Haemophilus influenzae type b is known in the prior art, and especially through the article "Quantitative and Qualitative Analyses of Serum Antibodies Elicited in Adults by Haemophilus influenzae Type b and Pneumococcus Type 6A Capsular Polysaccharide Tetanus Toxoid Conjugates" Rachel Schneerson et al, Infect. Immun. May 1986. This antigen is formed by a capsular polysaccharide of the bacteria, polyribosylribitol phosphate (or PRP), which is made T-dependent owing to coupling to a carrier protein, tetanus anatoxin. Trials carried out on rhesus children have shown, as this article reports, that the immune response was at one and the same time greater and earlier if the antigen was associated with aluminium hydroxide. However, as another article entitled "Clinical and Immunologic responses to the capsular polysaccharide of Haemophilus influenzae type b alone or conjugated to tetanus toxoid in 18-23 monthold children", Bo A. Claesson and al, The Journal of Pediatrics, May 1988, points out, it was noticed that this antigen, adsorbed on aluminium hydroxide, was less immunogenic after storage than the antigen kept in saline solution, which may be due to degradation of the polysaccharide. In order to resolve this problem of stability of the PRP-T, it was proposed in the prior art to lyophilize it. This solution, even though it allows the antigen to retain its immunogenic character in the course of time, shows some disadvantages, however, especially at the manufacturing level; the lyophilization and the particular operations of conditioning which it requires complicates the production process, which increases the cost. In addition, at the time of administration, it is necessary to take up the lyophilizate again, which means that it is necessary to have in addition to the lyophilizate a liquid for taking up this lyophilizate; this operation represents a supplementary constraint for the practitioner and presents, like any manipulation, the risk of being carried out badly. Web site: http://www.delphion.com/details?pn=US06333036__

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Vaccine compositions Inventor(s): Chatfield; Steven Neville (London, GB), Dougan; Gordon (London, GB), Hormaeche; Carlos Estenio (Newcastle upon Tyne, GB), Khan; Mohammed Anjam (Newcastle upon Tyne, GB) Assignee(s): Medeva Holdings B.V. (Amsterdam, NL) Patent Number: 6,488,926 Date filed: July 19, 1996 Abstract: The invention provides a DNA construct comprising a DNA sequence encoding a fusion protein of the formula: TetC-(Z).sub.a -Het, wherein: TetC is the C fragment of tetanus toxin, or a protein comprising the epitopes thereof; Het is a heterologous protein, Z is an amino acid, and a is zero or a positive integer, provided that (Z).sub.a does not include the sequence Gly-Pro. The invention also provides replicable expression vectors containing the constructs, bacteria transformed with the constructs, the fusion proteins per se and vaccine compositions formed from the fusion proteins or attenuated bacteria expressing the fusion proteins. Excerpt(s): This invention relates to DNA constructs, replicable expression vectors containing the constructs, bacteria containing the constructs and vaccines containing the bacteria or fusion proteins expressed therefrom. More particularly, the invention relates to novel DNA constructs encoding the C-fragment of tetanus toxin, and to fusion proteins containing tetanus toxin C-fragment. It is known to prepare DNA constructs encoding two or more heterologous proteins with a view to expressing the proteins in a suitable host as a single fusion protein. However, it has often been found that fusing two proteins together in this way leads to an incorrectly folded chimaeric protein which no longer retains the properties of the individual components. For example, the B-subunits of the Vibrio cholerae (CT-B) and E. coli (LT-B) enterotoxins are powerful mucosal immunogens but genetic fusions to these subunits can alter the structure and properties of the carriers and hence their immunogenicity (see M. Sandkvist et al. J. Bacteriol. 169, pp4570-6, 1987, Clements et al. 1990 and M. Lipscombe et al. Mol. Microbiol. 5, pp 1385, 1990). Moreover, many heterologous proteins expressed in bacteria are not produced in soluble properly folded or active forms and tend to accumulate as insoluble aggregates (see C. Schein et al. Bio/Technology 6, pp 291-4, 1988 and R. Halenbeck et al. Bio/Technology 7, pp 710-5, 1989. In our earlier unpublished international patent application PCT/GB93/01617, it is disclosed that by providing a DNA sequence encoding tetanus toxin C-fragment (TetC) linked via a "hinge region" to a second sequence encoding an antigen, the expression of the sequence in bacterial cells is enhanced relative to constructs wherein the C-fragment is absent. For example, the expression level of the full length P28 glutathione S-tranferase protein of S. mansoni when expressed as a fusion to TetC from the nirB promoter was greater than when the P28 protein was expressed alone from the nirB promoter. The TetC fusion to the full length P28 protein of S. mansoni was soluble and expressed in both E. coli and S. typhimurium. In addition, the TetC-P28 fusion protein was capable of being affinity purified by a glutathione agarose matrix, suggesting that the P28 had folded correctly to adopt a conformation still capable of binding to its natural substrate. It was previously considered that a hinge region, which typically is a sequence encoding a high proportion of proline and/or glycine amino acids, is essential for promoting the independent folding of both the TetC and the antigenic protein fused thereto. However, it has now been discovered, surprisingly in view of the previous studies on CT-B and LT-B referred to above, that when the hinge region is omitted between the TetC and a

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second antigen such as P28, the proteins making up the fusion do exhibit correct folding as evidenced by affinity purification on a glutathione agarose matrix. Web site: http://www.delphion.com/details?pn=US06488926__ •

Vaccine compositions for mucosal delivery Inventor(s): Dougan; Gordon (London, GB), Roberts; Mark (London, GB) Assignee(s): Medeva Holdings, B.V. (Amsterdam, NL) Patent Number: 6,562,352 Date filed: October 28, 1997 Abstract: The invention provides the use of an antigen which is a mucosally immunogenically active substance comprising the 50 kD C fragment of tetanus toxin, an immunogenic fragment thereof, or a derivative thereof formed by amino acid deletion, substitution or insertion for the manufacture of a vaccine composition for administration to a mucosal surface to induce an immune response in the mucosal surface against tetanus infection. The Vaccine composition preferably contains the P.69 outer membrane protein of B. pertussis, and B. pertussis filamentous haemaglutiuin. The invention also provides vaccine compositions per se and a method of treating tetanus and optionally whooping cough using the vaccine compositions. Excerpt(s): The present invention relates to vaccine compositions for delivery to mucosal surfaces, and to a method of inducing, in a mammal, an immune response to an antigen or a mixture of antigens by delivering the antigen or mixture of antigens to a mucosal surface of the mammal. More particularly, the present invention relates to vaccine compositions for inoculating a mammal such as a human against tetanus and B. pertussis infections. It has long been the practice of clinicians to immunise human infants against a variety of common diseases by means of mixed vaccines which are directed against a plurality of diseases. For example, multiple-component vaccine compositions directed against diphtheria, tetanus and whooping cough have been available for a considerable number of years. Such vaccines have hitherto been administered by injection. The advantages of multiple-component vaccines are readily apparent in that the patient (usually an infant) is subjected to a much smaller number of potentially distressing injections than would otherwise be the case. Web site: http://www.delphion.com/details?pn=US06562352__

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Vaccine preparation comprising a bacterial toxin adjuvant Inventor(s): Aizawa; Chikara (Kanagawa, JP), Kurata; Takeshi (Tokyo, JP), Nagamine; Takashi (Kanagawa, JP), Tamura; Shinichi (Kanagawa, JP) Assignee(s): National Institute of Health (Tokyo, JP), The Kitasato Institute (Tokyo, JP) Patent Number: 5,182,109 Date filed: April 10, 1989 Abstract: A vaccine preparation comprising in combination a vaccine and a toxin or subunit thereof as an effective component. The toxin is preferably a bacterial toxin, e.g. cholera toxin, staphylococcal.alpha.-hemolysin, staphylococcal.delta.-hemolysin, vibrio thermostable direct hemolysin, pertussis toxin or E. coli heat-labile toxin. The toxin can be a B subunit or a part of a B subunit of a toxin. The vaccine can be influenza vaccine,

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pertussis vaccine, Japanese encephalitis vaccine, mixed vaccine of pertussis, diphtheria and tetanus toxoid, hepatitis B vaccine, rota vaccine, measles vaccine, rubella vaccine, mumps vaccine, combined vaccine of measles, rubella and mumps, or mycoplasma vaccine. The ratio of vaccine to toxin or subunit thereof is 1:0.0001-1:10,000 (w/v). The vaccine can be intranasal vaccine, or can be in injectable form, spray form or oral administration form. Excerpt(s): This invention relates to a vaccine preparation. More particularly the present invention relates to a vaccine preparation comprising a toxin or subunit thereof as an effective ingredient. Vaccines have been used for protection against various kinds of diseases and have provided good results. However, side reactions or insufficient effectiveness of vaccines have sometimes been observed and hence there has been a strong demand for their improvement. To reduce the side reactions of vaccines, it has been attempted to prepare more highly purified vaccines or to administer smaller amounts of vaccine. However, these efforts have only resulted in less effectiveness of the vaccine. At present, various vaccines for human therapy have been prepared from pathogens or components thereof. Therefore the contamination of components which comprise pathogens, or the medium which is used for culturing the pathogens, in a vaccine cannot be avoided; and this induces side effects of vaccine inoculation. Web site: http://www.delphion.com/details?pn=US05182109__

Patent Applications on Tetanus 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 tetanus: •

Acellular pertussis vaccine with diphthriae-and tetanus-toxoids Inventor(s): Florent, Patrick; (Brussels, BE), Stephenne, Jean; (Rixensart, BE), Vandecasserie, Christian; (Lasne, BE) Correspondence: Glaxosmithkline; Corporate Intellectual Property - Uw2220; P.O. Box 1539; King OF Prussia; PA; 19406-0939; US Patent Application Number: 20010014331 Date filed: April 6, 2001 Abstract: This invention relates to a diphtheria, tetanus and pertussis vaccine comprising a low dose of each of diphtheria toxoid (D), tetanus toxoid (T), pertussis toxin (PT), filamentous haemagglutinin (FHA) and pertactin (69K). The vaccine maintains an ability to prevent pertussis while showing exceptionally low reactogenicity. Combination vaccines comprising additional antigens are also provided. Excerpt(s): The present invention relates to new vaccine formulations, comprising a low dose of the 69 kda outer membrane protein of Bordetella pertussis (hereinafter termed `69 K` or `69 K antigen` or pertactin, disclosed in European Patent 0 162 639. Recombinant 69 K (P69) has been described by N F Fairweather et al, Symposium On Pertussis (Bethesda), Sep. 26-28 1990). The invention in particular relates to a vaccine comprising more than one antigen, especially a multivalent vaccine, that is: a vaccine for

10

This has been a common practice outside the United States prior to December 2000.

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the amelioration or treatment of more than one disease state, in which a low dose of 69 K is present. The present invention also relates to the production and use of such vaccines in medicine. It is known that 69 K is an important component of acellular pertussis vaccines (Pa vaccines) for the effective prevention of pertussis. A study on the dose responses of 5 acellular pertussis vaccines in healthy adults was published by the US National Institutes of Health (NIH) in May 1996 by Keitel, W. et al. Web site: http://appft1.uspto.gov/netahtml/PTO/search-bool.html •

Chimeric peptide immunogens Inventor(s): Grimes, Stephen; (Davis, CA), Michaeli, Dov; (Larkspur, CA), Stevens, Vernon C.; (Dublin, OH) Correspondence: White & Case Llp; Patent Department; 1155 Avenue OF The Americas; New York; NY; 10036; US Patent Application Number: 20020076416 Date filed: May 4, 2001 Abstract: Chimeric peptide epitopes can serve as effective immunogens against hormones and other small peptides or proteins. Thus, immunogenic peptides are selected from promiscuous Th epitopes and synthesized together with self antigenic peptide sequences fused with or without end to end spacer peptide interconnections. A peptide sequence which may be of the gonadotropin releasing hormone is linked with an immunogenic peptide sequence selected from a promiscuous Th-epitope of measles virus protein F, tetanus toxoid, or malaria protein CSP. Compositions of the chimeric immunogen are found effective in eliciting high and specific anti-GnRH antibody titers. Excerpt(s): This application claims priority from the provisional application No. 60/202,328, filed May 5, 2000 in the United States Patent and Trademark Offic. The invention is related to chimeric peptides having immunogenic efficacy, comprising a hormone epitope and promiscuous helper T-cell epitope for the production of high titers of anti-hormone antibodies. The success of an antigenic composition is linked to its immunogenicity, that is, the ability to produce a sufficiently high titer of antibodies to react or bind with the target antigen or so as to neutralize its effects. The immunogenicity depends on the effectiveness by which the antigen causes the body's immune system to mount a response which can be generally assessed on the basis of the antibody titer in the blood of the immunized animal or mammal including the human. Web site: http://appft1.uspto.gov/netahtml/PTO/search-bool.html

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Conjugate vaccine composed of the polysaccharide moiety of the lipopolysaccharide of Vibrio cholerae O139 bound to tetanus toxoid Inventor(s): Boutonnier, Alain; (Paris, FR), Fournier, Jean-Michel; (Paris, FR) Correspondence: Finnegan, Henderson, Farabow,; Garrett & Dunner, L.L.P.; 1300 I Street, N.W.; Washington; DC; 20005-3315; US Patent Application Number: 20030068324 Date filed: April 5, 2002 Abstract: The epidemic and pandemic potential of V. cholerae O139 is such that a vaccine against this newly emerged serogroup of V. cholerae is required. A conjugate

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made of the polysaccharide moiety (O-specific polysaccharide+core) of the lipopolysaccharide (LPS) of V. cholerae O139 (pmLPS) was prepared by derivatization of the pmLPS with adipic acid dihydrazide and coupling to tetanus toxoid (TT) by carbodiimide-mediated condensation. The immunologic properties of the conjugate were tested using BALB/c mice injected subcutaneously three times at 2 weeks interval and then a fourth time 4 weeks later. Mice were bled 7 days after each injection and then once each month for the following six months. LPS and TT antibody levels were determined by ELISA using immunoplates coated with either O139 LPS or TT. Both pmLPS and pmLPS-TT conjugate elicited low levels of IgM, peaking 5 weeks after the first immunization. The conjugate elicited high levels of IgG antibodies, peaking 3 months after the first immunization and declining slowly during the following 5 months. TT alone, or as a component of conjugate, induced mostly IgG antibodies. Antibodies elicited by the conjugate recognized both capsular polysaccharide (CP) and LPS from V. cholerae O139, and were vibriocidal. They were also protective in the neonatal mouse model of cholera infection. The conjugation of the O139 pmLPS, therefore, enhanced its immunogenicity and conferred T-dependent properties to this polysaccharide. Excerpt(s): This application is based on and claims the benefit of priority of U.S. Provisional Application Serial No. 60/281,783, filed Apr. 6, 2001 (Attorney Docket No. 03495-6067). The entire disclosure of this application is relied upon and incorporated by reference. Since the appearance of Vibrio cholerae O139 in the suburb of Madras in October 1992, epidemic cholera caused by this strain has spread rapidly throughout the Indian subcontinent (1). Clinical illness associated with V. cholerae O139 infection appears to be virtually identical to that due to V. cholerae O1 El Tor infections. However, in contrast to infection with V. cholerae O1, V. cholerae O139 infection has largely affected the adult population in V. cholerae O1 endemic areas, indicating a lack of protective immunity against this newly evolved strain (1). Presumably, there are differences between the immune responses against O1 and O139 strains, which may be of considerable importance in terms of protection (33). A quiescent period followed the appearance of V. cholerae O139 and it was thought that it was a one-time event. However, there was an upsurge of cases in Calcutta in 1996 and the O139 serogroup again became the dominant serogroup causing cholera in India by September 1996 (32). The O139 serogroup has remained present in India and Bangladesh since this last outbreak (15) and requires careful monitoring. The epidemic and pandemic potential of V. cholerae O139 poses a serious threat to developing countries, and a vaccine against this novel strain is therefore required. The absence of cross-protection between V. cholerae O1 and V. cholerae O 139 serogroups, documented in rabbits either immunized with live bacteria (2) or passively protected with sera of convalescent cholera patients (33), suggested that protection against cholera is LPS-specific. This is supported by the correlation observed between the protective effect of rabbit O139 antisera and anti-LPS Abs titers (25). Web site: http://appft1.uspto.gov/netahtml/PTO/search-bool.html

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Covalent coupling of botulinum toxin with polyethylene glycol Inventor(s): Allison, Anthony; (Belmont, CA) Correspondence: Swanson & Bratschun L.L.C.; 1745 Shea Center Drive; Suite 330; Highlands Ranch; CO; 80129; US Patent Application Number: 20020197278 Date filed: June 21, 2002 Abstract: Modified toxins including botulinum toxin or tetanus toxin coupled to polyethylene glycol, pharmaceutical compositions of modified toxins, and methods for their use are provided. The methods include treating inappropriate muscle contraction, and treatments for cosmetic purposes. Excerpt(s): This application claims the benefit of U.S. Provisional Application No. 60/299,807, entitled "Covalent Coupling of Botulinum Toxin with Polyethylene Glycol," filed on Jun. 21, 2001. The present invention improves the efficacy of botulinum toxin for the treatment of disorders associated with inappropriate muscle contraction and for cosmetic applications. The toxin is modified so as to decrease its side effects and prolong its clinical utility. The neurotoxins produced by the bacterium Clostridium botulinum exert their paralytic effect at the neuromuscular junction by preventing the release of acetylcholine. Seven serologically distinct botulinum toxins, designated A through G, have been characterized, as well as tetanus toxin. These toxins have similar molecular weights (about 150 kDa) and subunit structures, as well as sequence homologies. The toxins comprise a short peptide chain of about 50 kDa which is considered to be responsible for the toxic properties, and a larger peptide chain of about 100 kDa which is considered to be necessary to enable attachment and penetration of the presynaptic membrane. The short and long chains are linked together by means of disulfide bridges. Although the target proteins differ, all botulinum toxins are believed to exert their neuroparalytic effects by the same mechanism, suppression of acetylcholine release from nerve terminals (reviewed by Brin, M. F. Botulinum toxin: chemistry, pharmacology, toxicology, and immunology. Muscle and Nerve, Supplement 6:S146-168, 1997, and the references cited therein, incorporated herein by reference). Web site: http://appft1.uspto.gov/netahtml/PTO/search-bool.html

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Fret protease assays for botulinum serotype A/E toxins Inventor(s): Aoki, Kei Roger; (Coto de Caza, CA), Fernandez-Salas, Ester; (Fullerton, CA), Steward, Lance E.; (Irvine, CA) Correspondence: Cathryn Campbell; Campbell & Flores Llp; 4370 LA Jolla Village Drive; 7th Floor; San Diego; CA; 92122; US Patent Application Number: 20030143650 Date filed: August 28, 2001 Abstract: The present invention provides clostridial toxin substrates useful in assaying for the protease activity of any clostridial toxin, including botulinum toxins of all serotypes as well as tetanus toxins. A clostridial toxin substrate of the invention contains a donor fluorophore; an acceptor having an absorbance spectrum overlapping the emission spectrum of the donor fluorophore; and a clostridial toxin recognition sequence that includes a cleavage site, where the cleavage site intervenes between the

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donor fluorophore and the acceptor and where, under the appropriate conditions, resonance energy transfer is exhibited between the donor fluorophore and the acceptor. Excerpt(s): The present invention relates generally to fluorescence resonance energy transfer and protease assays, for example, assays for protease activity of clostridial toxins such botulinum toxins and tetanus toxins, and more specifically, to intramolecularly quenched substrates and methods for assaying for clostridial toxin protease activity. The neuroparalytic syndrome of tetanus and the rare but potentially fatal disease, botulism, are caused by neurotoxins produced by bacteria of the genus Clostridium. These clostridial neurotoxins are highly potent and specific poisons of neural cells, with the human lethal dose of the botulinum toxins on the order of micrograms. Thus, the presence of even minute levels of botulinum toxins in foodstuffs represents a public health hazard that must be avoided through rigorous testing. However, in spite of their potentially deleterious effects, low controlled doses of botulinum neurotoxins have been successfully used as therapeutics. These toxins have been used in the therapeutic management of a variety of focal and segmental dystonias, of strabismus and other conditions in which a reversible depression of a cholinergic nerve terminal activity is desired. Established therapeutic uses of botulinum neurotoxins in humans include, for example, blepharospasm, hemifacial spasm, laringeal dysphonia, focal hyperhidrosis, hypersalivation, oromandibular dystonia, cervical dystonia, torticollis, strabismus, limbs dystonia, occupational cramps and myokymia (Rossetto et al, Toxicon 39:27-41 (2001)). Intramuscular injection of spastic tissue with small quantities of BoNT/A, for example, has been used effectively to treat spasticity due to brain injury, spinal cord injury, stroke, multiple sclerosis and cerebral palsy. Additional possible clinical uses of clostridial neurotoxins currently are being investigated. Web site: http://appft1.uspto.gov/netahtml/PTO/search-bool.html •

Hybrid protein for inhibiting the degranulation of mastocytes and the use thereof Inventor(s): Bigalke, Hans; (Hannover, DE), Frevert, Jurgen; (Berlin, DE) Correspondence: Gudrun E. Huckett; LONSSTR. 53; Wuppertal; 42289; DE Patent Application Number: 20030059912 Date filed: August 27, 2002 Abstract: A hybrid protein contains a protein that binds to a receptor of mastocytes and basophils and is endocyted by them. The protein can be IgE; IgE fragment; IgE Fc fragment; antibody against IgE receptor of mastocytes and basophils; fragment of the antibody against the IgE receptor of mastocytes and basophils; antibody against mastocyte specific potassium channel; and mast cell degranulating peptide. The hybrid protein also contains a protease cleaving proteins of the secretion process of the mastocytes and basophils so as to inhibit the secretion process without killing the mastocytes and basophils. The protease can be light chain Clostridium botulinum toxin; proteolytically active fragment of the light chain of a Clostridium botulinum toxin containing an amino acid sequence His-Xaa-Xaa-Xaa-His-Xaa-Xaa-His wherein Xaa is an amino acid; light chain of the tetanus toxin; proteolytically active fragment of the light chain of the tetanus toxin containing His-Asp-Leu-Ile-His-Val-Leu-His; IgA protease of Neisseria gonorrhoeae; and proteolytic domain of the IgA protease of Neisseria gonorrhoeae. Excerpt(s): This application is a continuation-in-part of U.S. patent application Ser. No. 09/700,540 filed Jan. 19, 2001 (35 USC 102(e) date), which is the national stage of

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PCT/EP99/03272 having an international filing date of May 19, 1999. Allergic reactions of the immediate type are characterized in that the patients concerned have formed antibodies of the IgE type against allergens (for example, pollen, house dust, mites, animal hair). These antibodies circulate not only in the blood but also bind to cells present in the tissue exhibiting in the plasma membrane a specific receptor for a portion of the IgE molecule, the Fc fragment (Fishman & Lorberboum-Galski 1997; Hamawy 1997). Cells with the IgE receptors are mastocytes and basophils exclusively. These cells are the cells effecting the allergic reaction of the immediate type. The stored vesicles containing vasoactive amines and prostaglandins, leukotrienes (derivatives of the arachidonic acid), and other effector molecules such as chymase (=effector molecules of the allergic reaction). The secretion process causing the release of these substances and resulting in the degranulation of the mastocytes, occurs through a specific and an unspecific mechanism. Once cells are mechanically destroyed, e.g., by a scratch on the skin, histamine is unspecifically released. At the wound the skin turns red. Nettles (edemas) are formed and the skin itches (triple response). Substances releasing specifically histamine are effective in relatively low concentrations and trigger the following cascade of responses (signal cascade): activation of phospholipase C-formation of the second messengers "diacylglycerol" and "IP3"--mobilization of calcium from cellular depots--fusion of the granules (vesicles) with the cell membrane-exocytosis of the granules without cytolysis--exchange of sodium against the positively charged histamine of the complex with heparin and a basic protein--release of the histamine from the granule matrix. Provided there is contact between the mastocytes of an allergic person and an allergen, the IgE molecules on the cell surface bind this allergen. Once allergen molecules are bound in sufficient amounts, aggregation of the receptors in the plasma membrane occurs. The aggregation is the specific stimulus for the induction of the above described signal cascade in the interior of the cell. The substances released induce the allergic symptoms (conjunctivitis, rhinitis, asthma, laryngeal edema, urticaria, blood pressure drop up to a pronounced anaphylactic shock). Peptides contained in the toxin of the bee such as the mast cell degranulating peptide (MCD) also effect a degranulation of the mastocytes. Additionally, some pharmaceuticals cause a specific release of histamine as an undesired effect. The release of histamine in humans is described for muscle relaxing agents, dextrans, acetylsalicylic acid (aspirin), morphine, antibiotics, contrast media in radiography, foreign sera etc. Web site: http://appft1.uspto.gov/netahtml/PTO/search-bool.html •

Hybrid proteins that migrate retrogradely and transynaptically into the CNS Inventor(s): Brulet, Philippe; (Paris, FR), Coen, Laurent; (Montreuil, FR), Pinzolas, Rosario Osta; (Zaragoza, ES) Correspondence: Finnegan, Henderson, Farabow, Garrett &; Dunner Llp; 1300 I Street, NW; Washington; DC; 20005; US Patent Application Number: 20030004121 Date filed: March 26, 2001 Abstract: The non-toxic proteolytic C fragment of tetanus toxin (TTC peptide) has the same ability to bind nerve cells and be retrogradely transported through a synapse as the native toxin. A hybrid protein encoded by the IacZ-TTC gene fusion retains the biological functions of both proteins in vivo, i.e. retrograde transynaptic transport of the TTC fragment and.beta.-gal enzymatic activity. After intramuscular injection, enzymatic activity could be detected in motoneurons and connected neurons of the brainstem

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areas. This strategy is useful for the delivery of a biological activity to neurons from the periphery to the central nervous system. Such a hybrid protein can also be used to map synaptic connections between neural cells. Excerpt(s): This application claims the benefit of Provisional Application No. 60/055,615, filed Aug. 14, 1997 and Provisional Application No. 60/065,236, filed Nov. 13, 1997. The entire disclosure of each of these provisional applications is relied upon and incorporated by reference herein. This invention relates to the use of part of tetanus toxin for delivering a composition to the central nervous system of a human or animal. This invention also relates to a hybrid fragment of tezanus toxin, a polynucleotide that hybridizes with natural tezanus toxin, and a composition containing the tetanus toxin fragment as an active molecule. Further, this invention relates to a vector comprising apromoter and a nucleic acid sequence encoding the tetanus toxin fragment. Tetanus toxin is produced by Clostridium tetani as an inactive, single, polypeptide chain of 150 kD composed of three 50 kD domains connected by protease-sensitive loops. The toxin is activated upon selective proteolytic cleavage, which generates two disulfide-linked chains: L (light, 50 kD) and H (heavy, 100 kD) [ Montecucco C. and Schiavo G. Q. Rev. Biophys., (1995), 28: 423-472]. Web site: http://appft1.uspto.gov/netahtml/PTO/search-bool.html •

Materials and methods relating to immune responses to fusion proteins Inventor(s): Rice, Jason; (Southampton, GB), Stevenson, Freda; (Southampton, GB) Correspondence: Dann, Dorfman, Herrell & Skillman; 1601 Market Street; Suite 2400; Philadelphia; PA; 19103-2307; US Patent Application Number: 20030158136 Date filed: March 27, 2003 Abstract: The invention provides nuecleic acid construct and nucleic acid expression vectors directing the expression of a fusion protein consisting or a disease peptide antigen and a first, domain of FrC of tetanus toxin. The invention provides nucleic acid (DNA) vaccines for use in inducing an immune response against a disease. There is also provided methods of producing nucleic acid constructs and vectors for use as nucleic acid (DNA) vaccines. Excerpt(s): The present invention relates to materials and methods involved in inducing an immune response in an individual. Particularly, but not exclusively, the present invention relates to DNA vaccines comprising Fragment C (FrC) domains as adjuvants for raising cytotoxic T lymphocytes (CTLs) against disease peptide antigens. While acellular vaccines are inevitably safer than vaccines based on whole organisms, a fully effective vaccine cannot normally be made from a single isolated constituent of a microorganism, and it is now clear that this is because of the need to activate more than one cell type to initiate an immune response. One consequence of this insight has been the development of conjugate vaccines. However, even conjugate vaccines are not usually strongly immunogenic on their own. Most of them require the addition of adjuvants: substances that enhance immunogenicity of antigens. It is thought that most, if not all, adjuvants act on antigen-presenting cells (APCs) and reflect the importance of these cells in initiating immune responses. H. influenzae polysaccharides, for example, have been conjugated to tetanus toxoid because infants are vaccinated routinely with this protein and their T cells are already primed against it. Web site: http://appft1.uspto.gov/netahtml/PTO/search-bool.html

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Multivalent vaccine composition Inventor(s): Boutriau, Dominique; (Rixensart, BE), Capiau, Carine; (Rixensart, BE), Desmons, Pierre Michel; (Rixensart, BE), Lemoine, Dominique; (Rixensart, BE), Poolman, Jan; (Rixensart, BE) Correspondence: Smithkline Beecham Corporation; Corporate Intellectual Property-us, Uw2220; P. O. Box 1539; King OF Prussia; PA; 19406-0939; US Patent Application Number: 20030180316 Date filed: March 26, 2003 Abstract: A multi-valent vaccine composition is described comprising a conjugate of the capsular polysaccharide of H. influenzae b not adsorbed onto an aluminium adjuvant salt, and two or more further bacterial polysaccharides. A multi-valent vaccine composition is also described comprising a whole-cell pertussis component, tetanus toxoid, diphtheria toxoid, Hepatitis B surface antigen, a conjugate of the capsular polysaccharide of H. influenzae b, and a conjugate of a capsular polysaccharide of N. meningitidis type A or C (or both). Furthermore, a multi-valent vaccine composition is described comprising a whole-cell pertussis component, tetanus toxoid, diphtheria toxoid, and a low dose of a conjugate of the capsular polysaccharide of H. influenzae b. Excerpt(s): The present invention relates to new combination vaccine formulations. Combination vaccines (which provide protection against multiple pathogens) are very desirable in order to minimise the number of immunisations required to confer protection against multiple pathogens, to lower administration costs, and to increase acceptance and coverage rates. The well-documented phenomenon of antigenic competition (or interference) complicates the development of multi-component vaccines. Antigenic interference refers to the observation that administering multiple antigens often results in a diminished response to certain antigens relative to the immune response observed when such antigens are administered individually. Combination vaccines are known which can prevent Bordetella pertussis, Clostridium tetani, Corynebacterium diphtheriae, and optionally Hepatitis B virus and/or Haemophilus influenzae type b (see, for instance, WO 93/24148 and WO 97/00697). The present invention concerns the manufacture of the most ambitious multi-valent vaccines to date, the administration of which can prevent or treat infection by Bordetella pertussis, Clostridium tetani, Corynebacterium diphtheriae, Hepatitis B virus, Haemophilus influenzae and N. meningitidis, and preferably also Hepatitis A virus and/or Polio virus, wherein the components of the vaccine do not significantly interfere with the immunological performance of any one component of the vaccine. Web site: http://appft1.uspto.gov/netahtml/PTO/search-bool.html

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Pneumococcus polysaccharide conjugates for use as vaccine against tetanus an diphtheria Inventor(s): Schultz, Dominique; (Lyon, FR) Correspondence: Mcdonnell Boehnen Hulbert & Berghoff; 300 South Wacker Drive; Suite 3200; Chicago; IL; 60606; US Patent Application Number: 20030099672 Date filed: September 17, 2002

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Abstract: The invention relates to the use of a composition comprising n Streptococcus pneumoniae polysaccharides conjugated to the tetanus toxoid and p Streptococcus pneumoniae polysaccharides conjugated to the diphtheria toxoid, for manufacturing a vaccine which protects against Clostridium tetani and/or Corynebacterium diphtheriae infections in which:(1) n and p are other than 1, with p being, however,.ltoreq.15,(2) 2.ltoreq.n+p.ltoreq.38,(3) the total amount of conjugated toxoid present in one vaccine dose is sufficient to induce protection against Clostridium tetani and/or Corynebacterium diphtheriae infections. Excerpt(s): The present invention relates to the use of vaccine combinations for preventing tetanus and/or diphtheria. In multivalent vaccine compositions, although there are many advantages in mutually combining the antigens so as to confer protection against several pathogens, negative interactions between the antigens may exist, the consequence of which is a relative drop in the immunogenicity of one or more components. This risk is all the greater given that the number of antigens, also called "valences", is considerable. Multivalent vaccines are known which comprise in particular diphtheria and tetanus valencies. Combining diphtheria, tetanus and whooping cough antigens with those of the polio virus leads to a decrease in the immune response to whooping cough. Web site: http://appft1.uspto.gov/netahtml/PTO/search-bool.html •

RECOMBINANT TOXIN FRAGMENTS Inventor(s): FOSTER, KEITH ALAN; (SURREY, GB), QUINN, CONRAD PADRAIG; (WILTSHIRE, GB), SHONE, CLIFFORD CHARLES; (WILTSHIRE, GB) Correspondence: Sterne Kessler Goldstein & Fox; 1100 New York Avenue N W; Suite 600; Washington; DC; 200053934 Patent Application Number: 20020044950 Date filed: February 23, 1999 Abstract: A polypeptide has first and second domains which enable the polypeptide to be translocated into a target cell or which increase the solubility of the polypeptide, or both, and further enable the polypeptide to cleave one or more vesicle or plasmamembrane associated proteins essential to exocytosis. The polypeptide thus combines useful properties of a clostridial toxin, such as a botulinum or tetanus toxin, without the toxicity associated with the natural molecule. The polypeptide can also contain a third domain that targets it to a specific cell, rendering the polypeptide useful in inhibition of exocytosis in target cells. Fusion proteins comprising the polypeptide, nucleic acids encoding the polypeptide and methods of making the polypeptide are also provided. Controlled activation of the polypeptide is possible and the polypeptide can be incorporated into vaccines and toxin assays. Excerpt(s): This invention relates to recombinant toxin fragments, to DNA encoding these fragments and to their uses such as in a vaccine and for in vitro and in vivo purposes. The clostridial neurotoxins are potent inhibitors of calcium-dependent neurotransmitter secretion in neuronal cells. They are currently considered to mediate this activity through a specific endoproteolytic cleavage of at least one of three vesicle or pre-synaptic membrane associated proteins VAMP, syntaxin or SNAP-25 which are central to the vesicle docking and membrane fusion events of neurotransmitter secretion. The neuronal cell targeting of tetanus and botulinum neurotoxins is considered to be a receptor mediated event following which the toxins become

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internalised and subsequently traffic to the appropriate intracellular compartment where they effect their endopeptidase activity. The clostridiai neurotoxins share a common architecture of a catalytic L-chain (LC, ca 50 kDa) disulphide linked to a receptor binding and translocating H-chain (HC, ca 100 kDa). The HC polypeptide is considered to comprise all or part of two distinct functional domains. The carboxyterminal half of the HC (ca 50 kDa), termed the H.sub.C domain, is involved in the high affinity, neurospecific binding of the neurotoxin to cell surface receptors on the target neuron, whilst the amino-terminal half, termed the H.sub.N domain (ca 50 kDa), is considered to mediate the translocation of at least some portion of the neurotoxin across cellular membranes such that the functional activity of the LC is expressed within the target cell. The H.sub.N domain also has the property, under conditions of iow pH, of forming ion-permeable channels in lipid membranes, this may in some manner relate to its translocation function. Web site: http://appft1.uspto.gov/netahtml/PTO/search-bool.html •

Recombinant toxin fragments Inventor(s): Chaddock, John; (Salisbury, GB), Foster, Keith Alan; (Salisbury, GB), Marks, Philip; (Salisbury, GB), Quinn, Conrad Padraig; (Lilburn, GA), Shone, Clifford Charles; (Alderbury, GB), Stancombe, Patrick; (Salisbury, GB), Sutton, J. Mark; (Salisbury, GB), Wayne, Jonathan; (Salisbury, GB) Correspondence: Sterne, Kessler, Goldstein & Fox Pllc; 1100 New York Avenue, N.W.; Washington; DC; 20005; US Patent Application Number: 20030166238 Date filed: September 12, 2002 Abstract: A single polypeptide is provided which comprises first and second domains. The first domain enables the polypeptide to cleave one or more vesicle or plasmamembrane associated proteins essential to exocytosis, and the second domain enables the polypeptide to be translocated into a target cell or increases the solubility of the polypeptide, or both. The polypeptide thus combines useful properties of a clostridial toxin, such as a botulinum or tetanus toxin, without the toxicity associated with the natural molecule. The polypeptide can also contain a third domain that targets it to a specific cell, rendering the polypeptide useful in inhibition of exocytosis in target cells. Fusion proteins comprising the polypeptide, nucleic acids encoding the polypeptide and methods of making the polypeptide are also provided. Controlled activation of the polypeptide is possible and the polypeptide can be incorporated into vaccines and toxin assays. Excerpt(s): This invention relates to recombinant toxin fragments, to DNA encoding these fragments and to their uses such as in a vaccine and for in vitro and in vivo purposes. The clostridial neurotoxins are potent inhibitors of calcium-dependent neurotransmitter secretion in neuronal cells. They are currently considered to mediate this activity through a specific endoproteolytic cleavage of at least one of three vesicle or pre-synaptic membrane associated proteins VAMP, syntaxin or SNAP-25 which are central to the vesicle docking and membrane fusion events of neurotransmitter secretion. The neuronal cell targeting of tetanus and botulinum neurotoxins is considered to be a receptor mediated event following which the toxins become internalised and subsequently traffic to the appropriate intracellular compartment where they effect their endopeptidase activity. The clostridial neurotoxins share a common architecture of a catalytic L-chain (LC, ca 50 kDa) disulphide linked to a

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receptor binding and translocating H-chain (HC, ca 100 kDa). The HC polypeptide is considered to comprise all or part of two distinct functional domains. The carboxyterminal half of the HC (ca 50 kDa), termed the H.sub.C domain, is involved in the high affinity, neurospecific binding of the neurotoxin to cell surface receptors on the target neuron, whilst the amino-terminal half, termed the H.sub.N domain (ca 50 kDa), is considered to mediate the translocation of at least some portion of the neurotoxin across cellular membranes such that the functional activity of the LC is expressed within the target cell. The H.sub.N domain also has the property, under conditions of low pH, of forming ion-permeable channels in lipid membranes, this may in some manner relate to its translocation function. 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 tetanus, 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 “tetanus” (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 tetanus. You can also use this procedure to view pending patent applications concerning tetanus. 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 TETANUS Overview This chapter provides bibliographic book references relating to tetanus. In addition to online booksellers such as www.amazon.com and www.bn.com, excellent sources for book titles on tetanus 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 “tetanus” (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 tetanus: •

Oral-Facial Emergencies: Diagnosis and Management Source: Portland, OR: JBK Publishing, Inc. 1994. 412 p. Contact: Available from Special Care Dentistry. 211 East Chicago Avenue, Chicago, IL 60611. (312) 440-2660. Fax (312) 440-2824. PRICE: $27.00 (member) or $30.00 (nonmember), plus shipping and handling; institutional prices and bulk orders available. ISBN: 0945892055. Summary: This book addresses a variety of orofacial injuries that are likely to be encountered in an acute care setting. Eleven chapters cover odontogenic and periodontal sources of oral pain, orofacial infections, dental disease and systemic infections, oral bleeding, acute mucogingival inflammatory conditions, lacerations, dentoalveolar trauma, facial fractures, temporomandibular disorders, extraoral sources of facial pain, and psychological and behavioral evaluations in the acute care setting. Each chapter defines the many types of problems that comprise the topic and then specifically

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discusses the management and treatment of each. The information presented is intended to be concise, with emphasis on tables and illustrations to promote the book's use as a quick clinical reference for acute care providers. Four appendices cover intraoral and extraoral injection techniques to achieve local anesthesia, a summary of intraoral and extraoral dental injections, pharmacological sedation for pediatric patients, and tetanus immunization schedule and prophylaxis recommendations. The handbook concludes with a subject index.

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 “tetanus” at online booksellers’ Web sites, you may discover non-medical books that use the generic term “tetanus” (or a synonym) in their titles. The following is indicative of the results you might find when searching for “tetanus” (sorted alphabetically by title; follow the hyperlink to view more details at Amazon.com): •

Adults need tetanus shots, too (SuDoc HE 20.4010/A:AD 9) by Evelyn Zamula; ISBN: B00010REH6; http://www.amazon.com/exec/obidos/ASIN/B00010REH6/icongroupinterna

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Botulinum and Tetanus Neurotoxins: Neurotransmission and Biomedical Aspects by Bibhuti R. Dasgupta (Editor) (1993); ISBN: 0306444127; http://www.amazon.com/exec/obidos/ASIN/0306444127/icongroupinterna

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Botulinum Neurotoxin and Tetanus Toxin by Lance L. Simpson (Editor); ISBN: 0126444455; http://www.amazon.com/exec/obidos/ASIN/0126444455/icongroupinterna

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Clostridial Neurotoxins: the Molecular Pathogenesis of Tetanus and Botulism by C. Montecucco (Editor), Cesare Monteucco; ISBN: 3540584528; http://www.amazon.com/exec/obidos/ASIN/3540584528/icongroupinterna

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Historische Aspekte der Tetanustherapie und der Immunisierung gegen Tetanus bis zum Ende des Ersten Weltkrieges by Christian Hertle; ISBN: 3820480102; http://www.amazon.com/exec/obidos/ASIN/3820480102/icongroupinterna

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Neonatal Tetanus Elimination Field Guide (Technical Paper (Pan American Health Organization), No. 35.); ISBN: 9275130353; http://www.amazon.com/exec/obidos/ASIN/9275130353/icongroupinterna

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Tetanus by Farokh Erach Udwadia (1994); ISBN: 0195635787; http://www.amazon.com/exec/obidos/ASIN/0195635787/icongroupinterna

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Tetanus by Veronesi; ISBN: 0444902031; http://www.amazon.com/exec/obidos/ASIN/0444902031/icongroupinterna

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Tetanus by E. B. Adams; ISBN: 0632060905; http://www.amazon.com/exec/obidos/ASIN/0632060905/icongroupinterna

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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 “tetanus” (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 •

Accelerated tetanus toxoid programme in North West Frontier Province, Pakistan. Author: UNICEF, Islamabad.; Year: 1937; [Islamabad]: UNICEF, Islamabad, [1988]

•

Active immunization against tetanus in man and in quinea-pigs: an experimental and clinical study Author: Ullberg-Olsson, Karin.; Year: 1951; Stockholm: [s.n.], 1975

•

An epidemiological study of tetanus in Iowa, by Franklin H. Top [et al. Author: Top, Franklin Henry,; Year: 1969; Iowa City] 1964

•

An integrated approach to high coverage control of measles, elimination of neonatal tetanus, eradication of poliomyelitis: introducing the high risk approach. Author: World Health Organization. Expanded Programme on Immunization.; Year: 1963; Geneva: Expanded Programme on Immunization, World Health Organization, 1993

•

Barbiturate poisoning and tetanus. Author: Johansen, Sophus H.; Year: 1968; Boston, Little, Brown, 1966

•

Birth care practice and neonatal tetanus in a rural area of Bangladesh Author: Islam, M. Shafiqual.; Year: 1960; Dacca, Bangladesh: International Centre for Diarrhoeal Disease Research, 1980

•

Guidelines for investigating suspected cases of neonatal tetanus. Author: World Health Organization. Expanded Programme on Immunization.; Year: 1953; Geneva: Expanded Programme on Immunization, World Health Organization, 1993

•

Manual for the production and control of vaccines: tetanus toxoid Author: World Health Organization.; Year: 1963; [Geneva]: WHO, [197-]

•

Principles on tetanus; proceedings. Sponsored by the Swiss Academy of Medical Sciences with the support of WHO. Edited by Leo Eckmann. Author: Eckmann, Leo.; Year: 1970; Bern, Huber [c1967]

•

Production and control of tetanus vaccine: a training curriculum. Author: World Health Organization.; Year: 1955; Geneva: World Health Organization in collaboration with National Public Health Institute, [1994]

•

Seventh International Conference on Tetanus: Copanello, Italy, 10-15 September, 1984; Year: 1955; Roma: Gangemi Publ. Co., 1985; ISBN: 8874481403

•

Studies on the antibody response in allergic and non-allergic men following antitetanus vaccination Author: Wiholm, Stig.; Year: 1954; Stockholm: [s.n.], 1972

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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•

Tetanus [by] E. B. Adams, D. R. Laurence [and] J. W. G. Smith. Author: Adams, E. B. (Edward Barry); Year: 1971; Oxford, Blackwell Scientific Publications [1969]; ISBN: 632060905

•

Tetanus; a team disease [by] Wesley Furste [and] Warren L. Wheeler. Author: Furste, Wesley.; Year: 1966; [Chicago, Year Book Medical Publishers, 1972]; ISBN: 0815199031 http://www.amazon.com/exec/obidos/ASIN/0815199031/icongroupinterna

•

Tetanus; prophylaxis and therapy. Tr. from the German with the author's additions to the German ed. Author: Eckmann, Leo.; Year: 1967; New York, Grune; Stratton [c1963]

•

The occurrence of tetanus in Finland; a clinical study [by] Gustaf Elfving and Kari Asp. Author: Elfving, Gustaf.; Year: 1969; Helsinki [Mercator] 1955

•

Third International Conference on Tetanus.; Year: 1967; Washington, Pan American Health Organization, 1972

•

Vaccination against whooping-cough, diphtheria and tetanus; outstanding questions posed and answered. Author: Research Defence Society (Great Britain); Year: 1969; [London] 1960

Chapters on Tetanus In order to find chapters that specifically relate to tetanus, an excellent source of abstracts is the Combined Health Information Database. You will need to limit your search to book chapters and tetanus 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 “tetanus” (or synonyms) into the “For these words:” box. The following is a typical result when searching for book chapters on tetanus: •

Maxillofacial Trauma and Head Injury Source: in Scully, C. and Cawson, R.A. Medical Problems in Dentistry. 4th ed. Woburn, MA: Butterworth-Heinemann. 1998. p. 454-469. Contact: Available from Butterworth-Heinemann. 225 Wildwood Avenue, Woburn, MA 01801-2041. (800) 366-2665 or (781) 904-2500. Fax (800) 446-6520 or (781) 933-6333. E-mail: [email protected]. Website: www.bh.com. PRICE: $110.00. ISBN: 0723610568. Summary: This chapter on maxillofacial trauma and head injury is from a text that covers the general medical and surgical conditions relevant to the oral health care sciences. Topics include the initial management of the patient with maxillofacial injuries, including airway and breathing, and hemorrhage; head injury, including taking the patient history, the examination, the admission of conscious patients to hospital, analgesia, clinical examination, radiography, blood analyses, observation, medical complication of head injuries, late sequelae of head injury, posttraumatic syndrome, and diabetes insipidus; complications of maxillofacial injuries, including cranial nerve injuries, orbital injuries, burns, adult respiratory distress syndrome (ARDS), injuries to the spinal cord, and atlanto-axial subluxation; the general and dental management of paraplegics; stab wounds; gunshot wounds; prevention of infection, including meningitis, wound infection, tetanus, and management of the wounded patient; and sports injuries. Child abuse is covered in a separate chapter. For each condition, the authors discuss general aspects, diagnosis and management issues, dental aspects, and

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patient care strategies. The chapter includes a summary of the points covered. 8 tables. 42 references.

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CHAPTER 8. MULTIMEDIA ON TETANUS Overview In this chapter, we show you how to keep current on multimedia sources of information on tetanus. 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.

Bibliography: Multimedia on Tetanus 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 tetanus (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 tetanus: •

Tetanus and its treatment [motion picture] Source: Mayo Clinic, and Mayo Foundation; Year: 1969; Format: Motion picture; Rochester, Minn.: The Clinic, 1969

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CHAPTER 9. PERIODICALS AND NEWS ON TETANUS Overview In this chapter, we suggest a number of news sources and present various periodicals that cover tetanus.

News Services and Press Releases One of the simplest ways of tracking press releases on tetanus 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 “tetanus” (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 tetanus. 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 “tetanus” (or synonyms). The following was recently listed in this archive for tetanus: •

Diphtheria-tetanus-pneumococcal vaccine elicits high antibody response Source: Reuters Medical News Date: June 27, 2003

•

UN launches drive against tetanus in Afghanistan Source: Reuters Medical News Date: February 03, 2003

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•

Intrathecal anti-tetanus immunoglobulin improves outcome in childhood tetanus Source: Reuters Medical News Date: August 20, 2002

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Three cases of tetanus reported in Puerto Rico--two fatal Source: Reuters Medical News Date: July 22, 2002

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CDC lifts restriction on tetanus, diphtheria boosters after Aventis builds up supply Source: Reuters Industry Breifing Date: June 20, 2002

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Aventis Pasteur increases tetanus vaccine availability for physicians Source: Reuters Industry Breifing Date: May 09, 2002

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Many in US not protected against diphtheria and tetanus Source: Reuters Medical News Date: May 06, 2002

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Needle-free tetanus vaccination effective in mice Source: Reuters Medical News Date: November 20, 2001

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Aventis eyes managed-care field; ups production of tetanus/diptheria booster Source: Reuters Industry Breifing Date: May 30, 2001

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Shortage of adult tetanus vaccine causes rationing Source: Reuters Medical News Date: February 20, 2001

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Adult tetanus vaccine shortage in US triggers nationwide rationing Source: Reuters Industry Breifing Date: February 20, 2001

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Shortage of tetanus and diphtheria toxoids anticipated Source: Reuters Industry Breifing Date: November 16, 2000

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Tetanus infection in early childhood in India occurs mainly through the ear Source: Reuters Medical News Date: August 08, 2000

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Becton Dickinson donates syringes to tetanus initiative Source: Reuters Medical News Date: December 23, 1999

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Gates Foundation donates $26 million to tetanus program Source: Reuters Medical News Date: November 23, 1999

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Tetanus-diphtheria toxoids booster can be offered to young adolescents Source: Reuters Medical News Date: January 18, 1999

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Tetanus immunization protects elderly for at least a year Source: Reuters Medical News Date: August 18, 1998

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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 “tetanus” (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 “tetanus” (or synonyms). If you know the name of a company that is relevant to tetanus, 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/. 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 “tetanus” (or synonyms).

Academic Periodicals covering Tetanus Numerous periodicals are currently indexed within the National Library of Medicine’s PubMed database that are known to publish articles relating to tetanus. In addition to these

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sources, you can search for articles covering tetanus 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 tetanus. 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 nonprofit 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). Below, we have compiled a list of medications associated with tetanus. If you would like more information on a particular medication, the provided hyperlinks will direct you to ample documentation (e.g. typical dosage, side effects, drug-interaction risks, etc.). The

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following drugs have been mentioned in the Pharmacopeia and other sources as being potentially applicable to tetanus: Anticonvulsants, Hydantoin •

Systemic - U.S. Brands: Cerebyx; Dilantin; Dilantin Infatabs; Dilantin Kapseals; Dilantin-125; Mesantoin; Peganone; Phenytex http://www.nlm.nih.gov/medlineplus/druginfo/uspdi/202052.html

Anticonvulsants, Succinimide •

Systemic - U.S. Brands: Celontin; Zarontin http://www.nlm.nih.gov/medlineplus/druginfo/uspdi/202053.html

Clindamycin •

Systemic - U.S. Brands: Cleocin http://www.nlm.nih.gov/medlineplus/druginfo/uspdi/202145.html

•

Topical - U.S. Brands: Clinda-Derm http://www.nlm.nih.gov/medlineplus/druginfo/uspdi/202146.html

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Vaginal - U.S. Brands: Cleocin http://www.nlm.nih.gov/medlineplus/druginfo/uspdi/202700.html

Diphtheria and Tetanus Toxoids and Pertussis Vaccine Adsorbed •

Systemic - U.S. Brands: Acel-Imune; Certiva; Infanrix; Tripedia http://www.nlm.nih.gov/medlineplus/druginfo/uspdi/202201.html

Doxycycline •

Dental - U.S. Brands: Atridox http://www.nlm.nih.gov/medlineplus/druginfo/uspdi/203716.html

Erythromycin •

Ophthalmic - U.S. Brands: Ilotycin http://www.nlm.nih.gov/medlineplus/druginfo/uspdi/202220.html

Metronidazole •

Systemic - U.S. Brands: Flagyl; Protostat http://www.nlm.nih.gov/medlineplus/druginfo/uspdi/202365.html

•

Vaginal - U.S. Brands: MetroGel-Vaginal http://www.nlm.nih.gov/medlineplus/druginfo/uspdi/202704.html

Phenothiazines •

Systemic - U.S. Brands: Chlorpromazine Hydrochloride Intensol; Compazine; Compazine Spansule; Mellaril; Mellaril Concentrate; Mellaril-S; Permitil; Permitil Concentrate; Prolixin; Prolixin Concentrate; Prolixin Decanoate; Prolixin Enanthate; Serentil; Serentil Concentrate; Ste http://www.nlm.nih.gov/medlineplus/druginfo/uspdi/202457.html

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Skeletal Muscle Relaxants •

Systemic - U.S. Brands: Carbacot; EZE-DS; Maolate; Paraflex; Parafon Forte DSC; Relaxazone; Remular; Remular-S; Robaxin; Robaxin-750; Skelaxin; Skelex; Soma; Strifon Forte DSC; Vanadom http://www.nlm.nih.gov/medlineplus/druginfo/uspdi/202523.html

Tetanus Antitoxin •

Systemic http://www.nlm.nih.gov/medlineplus/druginfo/uspdi/202457.html

Tetanus Immune Globulin •

Systemic - U.S. Brands: BayTet http://www.nlm.nih.gov/medlineplus/druginfo/uspdi/202908.html

Tetanus Toxoid •

Systemic http://www.nlm.nih.gov/medlineplus/druginfo/uspdi/202908.html

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.

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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

•

National Eye Institute (NEI); guidelines available at http://www.nei.nih.gov/order/index.htm

•

National Heart, Lung, and Blood Institute (NHLBI); guidelines available at http://www.nhlbi.nih.gov/guidelines/index.htm

•

National Human Genome Research Institute (NHGRI); research available at http://www.genome.gov/page.cfm?pageID=10000375

•

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

•

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

•

National Center for Complementary and Alternative Medicine (NCCAM); health information available at http://nccam.nih.gov/health/

•

National Center for Research Resources (NCRR); various information directories available at http://www.ncrr.nih.gov/publications.asp

•

Office of Rare Diseases; various fact sheets available at http://rarediseases.info.nih.gov/html/resources/rep_pubs.html

•

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/

•

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

•

Cancer Information: Access to cancer-oriented databases: http://www.nlm.nih.gov/databases/databases_cancer.html

•

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/

•

Chemical Information: Provides links to various chemical databases and references: http://sis.nlm.nih.gov/Chem/ChemMain.html

•

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

•

Space Life Sciences: Provides links and information to space-based research (including NASA): http://www.nlm.nih.gov/databases/databases_space.html

•

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 Combined Health Information Database

A comprehensive source of information on clinical guidelines written for professionals is the Combined Health Information Database. You will need to limit your search to one of the following: Brochure/Pamphlet, Fact Sheet, or Information Package, and “tetanus” using the “Detailed Search” option. Go directly to the following hyperlink: 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 the publication date, select “All Years.” Select your preferred language and the format option “Fact Sheet.” Type “tetanus” (or synonyms) into the “For these words:” box. The following is a sample result: •

Special Programme on AIDS, WHO Consultation on HIV and Routine Childhood Immunization, Report, Geneva, Switzerland, 12-13 August 1987 Contact: World Health Organization, Joint United Nations Programme on HIV/AIDS, 20 Avenue Appia, CH-1211 Geneva, http://www.unaids.org. Summary: On August 12-13, 1987, the World Health Organization Special Program on Acquired Immune Deficiency Syndrome (AIDS) and the Expanded Program on Immunization sponsored a joint consultation in Geneva. International participants reviewed the worldwide epidemiology and the natural history of human immunodeficiency virus (HIV) in children and the epidemiology and clinical manifestations of measles, tetanus, diptheria, pertussis, poliomyelitis, and tuberculosis (TB). Also considered was available data on safety, immunogenicity, and efficacy of the six EPI vaccines in children with HIV infection and the potential of live and inactivated vaccines to accelerate the course of HIV infection in afflicted children. The review suggested that while the likelihood of successful immunization may be reduced in some HIV-infected individuals, the risk of serious adverse effects or of accelerating the course of infection by administration of multiple antigens is low and is likely to be negligible in contrast to other natural sources of antigenic stimulation. Consequently, it was concluded that children should continue to be immunized with EPI antigens according to standard schedules. The BCG vaccine should be withheld where risk of TB is low or where the individual is HIV symptomatic.

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. 15 16

Adapted from NLM: http://gateway.nlm.nih.gov/gw/Cmd?Overview.x.

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).

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Type “tetanus” (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 18559 910 146 300 0 19915

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 “tetanus” (or synonyms) at the following Web site: http://text.nlm.nih.gov.

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/. 17

Adapted from HSTAT: http://www.nlm.nih.gov/pubs/factsheets/hstat.html.

18

The HSTAT URL is http://hstat.nlm.nih.gov/.

19

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.

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.

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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/.

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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 tetanus 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 tetanus. 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 tetanus. 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 “tetanus”:

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•

Guides on tetanus Tetanus http://www.nlm.nih.gov/medlineplus/tetanus.html

•

Other guides Childhood Immunization http://www.nlm.nih.gov/medlineplus/childhoodimmunization.html Diphtheria http://www.nlm.nih.gov/medlineplus/diphtheria.html Whooping Cough http://www.nlm.nih.gov/medlineplus/whoopingcough.html

Within the health topic page dedicated to tetanus, the following was listed: •

General/Overviews Infectious Diseases - Tetanus Source: University of Utah, Health Sciences Center http://www.med.utah.edu/healthinfo/pediatric/Infectious/tetanus.htm Tetanus Overview Source: National Coalition for Adult Immunization, National Foundation for Infectious Diseases http://www.nfid.org/powerof10/section2/overview-tetanus.html

•

Specific Conditions/Aspects Facts about Tetanus for Adults Source: National Coalition for Adult Immunization, National Foundation for Infectious Diseases http://www.nfid.org/powerof10/section2/factsheet-tetanus.html

•

Children Tetanus Source: Nemours Foundation http://kidshealth.org/parent/infections/bacterial_viral/tetanus.html

•

Organizations Centers for Disease Control and Prevention, National Immunization Program Source: National Immunization Program http://www.cdc.gov/nip/ National Institute of Allergy and Infectious Diseases http://www.niaid.nih.gov/ National Institute on Aging http://www.nia.nih.gov/

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Pictures/Diagrams Tetanus Photos Source: Immunization Action Coalition http://www.vaccineinformation.org/tetanus/photos.asp

•

Prevention/Screening Are You at Risk for Tetanus or Diphtheria? Source: National Coalition for Adult Immunization, National Foundation for Infectious Diseases http://www.nfid.org/powerof10/section2/areyouatrisk.html Diphtheria, Tetanus, and Pertussis Vaccines http://www.cdc.gov/nip/publications/VIS/vis-dtp.pdf Do I Need a Tetanus Shot? Source: American College of Emergency Physicians http://www.acep.org/1%2C2734%2C0.html

•

Research Immunity to Diphtheria and Tetanus in the United States Source: American College of Physicians http://www.annals.org/cgi/content/full/136/9/I30

•

Statistics Are You Protected from Tetanus and Diphtheria? Source: National Coalition for Adult Immunization, National Foundation for Infectious Diseases http://www.nfid.org/powerof10/section2/areyouprotected.html

•

Teenagers Tetanus Source: Nemours Foundation http://kidshealth.org/teen/infections/bacterial_viral/tetanus.html

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 tetanus. 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.

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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: •

Get Your Hepatitis B Vaccine: It Takes 3 Shots Source: Trenton, NJ: New Jersey Department of Health and Senior Services. 1998. [2 p.]. Contact: Available from New Jersey Department of Health and Senior Services, Immunization Program. P.O. Box 369, Trenton, NJ 08625-0369. (609) 588-7512. Fax (609) 588-7431. PRICE: Single copy free; limited quantities available. Summary: Hepatitis B is a serious disease that affects the liver. Some people who become infected with the virus later develop serious liver disease, such as liver cancer. This brochure familiarizes teenagers with hepatitis B and the vaccine available to prevent the disease. The hepatitis B virus (HBV) is found in blood and body fluids such as sexual secretions. It is spread from one person to another after coming in contact with even the smallest amount of infected blood or body fluids. HBV can cause many different symptoms of sickness (including flu like symptoms, jaundice, loss of appetite) or no symptoms at all. Many infected persons do not feel sick and may not know they have the disease unless they get a blood test for hepatitis B. Since they have no idea they are infected with the virus, they can unknowingly infect others. Hepatitis B is also considered a sexually transmitted disease (STD). The hepatitis B vaccine, given in a series of 3 shots over a period of 6 months, can protect against infection. The brochure concludes by recommending other immunizations that teenagers should have, including MMR (measles, mumps, rubella), Td (tetanus, diphtheria), and varicella (chickenpox).

•

Why Older Children Need Shots Source: South Deerfield, MA: Channing L. Bete Company, Inc. 1996. 8 p. Contact: Available from Channing L. Bete Company, Inc. 200 State Road, South Deerfield, MA 01373-0200. (800) 628-7733. Fax (800) 499-6464. PRICE: $1.25 each for 1-24 copies; discounts available for larger orders. Summary: This booklet encourages parents of young adolescents and teenagers to make sure their children receive the recommended immunizations. After an introductory section explaining why 'shots are not just for babies,' the booklet describes immunization for hepatitis B, chicken pox, MMR (measles, mumps, rubella), and Td (tetanus, diphtheria). Other topics include the importance of keeping good records, protection against polio, and the need for regular health care. The back cover of the booklet can be personalized by the printer. The booklet is illustrated with simple line drawings.

•

Shooting Up. A Sure Way to Come Down Contact: AIDS Resource Center of Wisconsin, Green Bay Office, 824 S Broadway, Green Bay, WI, 54304-2735, (920) 437-7400, http://www.arcw.org/Green%20Bay.htm. AIDS Resource Center of Wisconsin, Appleton Office, 120 N Morrison St Ste 201, Appleton, WI, 54911, (920) 733-2068, http://www.arcw.org. Summary: This brochure warns Intravenous drug users (IVDU's) of the dangers they face from IV-needle sharing, including the risk of contracting Acquired immunodeficiency syndrome (AIDS). It tells readers that sharing needles also shares diseases, such as hepatitis B, Human immunodeficiency virus (HIV) infection, endocarditis, and tetanus. Symptoms of each disease are given. The brochure says that

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IVDU's can reduce their risk of infection by not sharing needles, by clearing their equipment and their skin, and by staying healthy. •

Summary of Recommendations for Adult Immunization Source: St. Paul, MN: Immunization Action Coalition. 1998. 2 p. Contact: Available from Hepatitis B Coalition. 1573 Selby Avenue, Suite 229, St. Paul, MN 55104-6328. (612) 647-9009. Fax (651) 647-9131. E-mail: [email protected]. Website: www.immunize.org. PRICE: Full-text available online at no charge; $1.00 for single copy. Item number: P2011. Summary: This chart summarizes recommendations for adult immunization. The chart notes the vaccine name and storage temperature, for whom it is recommended, the usual schedule, the schedule for those who have fallen behind, contraindications and precautions, rules of simultaneous administration, and route (intramuscular, subcutaneous). Recommendations are provided for influenza, pneumococcal, hepatitis B, hepatitis A, TD (tetanus, diphtheria), MMR (measles, mumps, rubella), varicella (chicken pox), and polio vaccines. The chart lists information adapted from the Advisory Committee on Immunization Practices (ACIP). The chart was developed to combine the recommendations of adult immunization onto one page. It was devised especially to assist health care workers in determining appropriate use and scheduling of vaccines. The chart can be posted in immunization clinics or clinicians' offices. (AA-M).

•

Immunizations for Babies: A Guide for Parents Source: St. Paul, MN: Immunization Action Coalition. 1995. 1 p. Contact: Available from Hepatitis B Coalition. 1573 Selby Avenue, Suite 229, St. Paul, MN 55104. (612) 647-9009. Fax (612) 647-9131. PRICE: $1.00. Summary: This fact sheet displays the immunizations needed for babies. The information is provided in graphic form: at the left side of the page are the ages for immunization (birth, 1 to 2 months, 2 months, 4 months, 6 months, 12 months, and 15 months). Across from each age notation is a line drawing of a syringe, with the abbreviated name of the shot that is to be given at that age. Vaccines included are HepB (hepatitis B), DTaP (diphtheria, tetanus and pertussis), Hib (haemophilus influenzae type b), polio, MMR (measles, mumps, rubella), and Var (varicella zoster, or chicken pox). The fact sheet encourages parents to check with the clinic to make sure the baby is getting immunized on time and to ask for a record card with the dates of the baby's shots.

•

Exposure to Blood/Body Fluids Contaminated With Blood From a Source of Known or Probable HIV Infection (Including Needlestick/Sharps Injuries) Contact: Australian National Council on AIDS Hepatitis C and Related Diseases, GPO Box 9848 MDP 13, Canberra, (011) 62897767, http://www.ancahrd.org. Summary: This fact sheet lists, and defines, the levels of parenteral exposure to Human immunodeficiency virus (HIV) ranging from massive, through definite, possible, doubtful, and non-exposure. It then outlines, in separate sections, the actions that should be taken by the person who has been exposed; the responsibilities of supervisors, managers, and occupational health and safety officers; and protocols to be followed by medical practitioners who are treating the exposure. Specific guidelines are given for treatment if the patient has been exposed to HIV, Hepatitis B, Hepatitis C, or tetanus. Prophylactic treatment with azidothymidine is explained.

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•

Are You 11-19 Years Old? Then You Need to Be Vaccinated Against These Serious Diseases! Source: St. Paul, MN: Immunization Action Coalition. 1996. 1 p. Contact: Available from Hepatitis B Coalition. 1573 Selby Avenue, Suite 229, St. Paul, MN 55104. (612) 647-9009. Fax (612) 647-9131. PRICE: $1.00. Summary: This fact sheet reviews the immunizations needed for adolescents (ages 11 to 19 years). The fact sheet reminds readers that getting immunized is a lifelong, lifeprotecting job. The fact sheet lists the vaccines and the recommendations for each. Included are: hepatitis B, MMR (measles, mumps, rubella), Td (tetanus, diphtheria), varicella (chicken pox), hepatitis A, influenza vaccine (flu shot), and pneumococcal vaccine. The fact sheet also notes recommendations for people who travel outside the U.S. The fact sheet is illustrated with line drawings of young adults.

•

Vaccinations for Adults With Hepatitis C Virus Infection Contact: Immunization Action Coalition, 1573 Selby Ave Ste 234, St Paul, MN, 55104, (651) 647-9009, http://www.immunize.org. Summary: This fact sheet, written for individuals the hepatitis C virus (HCV), makes recommendations regarding vaccinations for persons with compromised immune systems. The fact sheet lists several diseases that can be prevented with periodic vaccinations. It provides a recommended schedule of shots for HCV-positive individuals, their caregivers, and roommates regarding the following diseases: pneumococcal, influenza, hepatitis A and B, tetanus/diptheria, measles, mumps, rubella, and varicella.

•

Put prevention into practice: Education and action kit Source: Washington, DC: Public Health Service, U.S. Department of Health and Human Services. 1994. 2 health guides; 1 clinician's handbook, 3 flow charts, 16 chart stickers, 2 posters. Contact: Available from Superintendent of Documents, U.S. Government Printing Office, P.O. Box 371954, Pittsburgh, PA 15250-7954. Telephone: (202) 512-1991 for public information (D.C. office) or (202) 512-1800 for ordering and publication information (D.C. office) / fax: (202) 512-1293 (public information); (202) 512-2250 (ordering) / Web site: http://www.access.gpo.gov. $57.00. Summary: This kit, produced through the 'Put Prevention into Practice' initiative of the Public Health Service, contains materials to facilitate and enhance the practice of preventive medicine for both clinicians and the public. The 'Clinician's Handbook of Preventive Services' is the core element of the kit. After an overview of preventive care implementation, this manual provides guidelines for screening, immunization/prophylaxis, and counseling divided into two major sections, one for children and adolescents and one for adults and older adults. The screening section for children and adolescents focuses on anemia, blood pressure, body measurement, cholesterol, depression and suicide, hearing, lead, newborn screening, tuberculosis, urinalysis, and vision. The immunization/prophylaxis section covers DPT, Hepatitis B, MMR, Polio myelitis, and Haemophilus influenzae Type b inoculations. The counseling section focuses on alcohol and drug use, dental and oral health, nutrition, physical activity, safety, STDs and HIV infection, tobacco use, unintended pregnancy, and firearms and violent behavior. Screening guidelines for adults cover the same areas as previously mentioned along with cancer detection, cognitive and functional

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impairment, fecal occult blood, sigmoidoscopy, and thyroid function. The adult immunization/prophylaxis section contains guidelines on aspirin, hormone replacement therapy, hepatitis B, influenza, pneumococcus, rubella, and tetanus and diphtheria. Counseling guidelines for adults cover the same areas as mentioned above with the addition of polypharmacy. Appendices include risk factor summary tables, a bibliography of references, a varicella (chicken pox) vaccination statement, and a copyright disclaimer. Each section contains implementation tools such as questionnaires, charts, and protocols. The pocket-sized guides for children and adults measure 6 inches high and are designed for patients to take with them on visits to their physician. Each provides space for patients and physicians to enter health information such as blood pressure, weight, cholesterol levels, and immunizations. The guides also provide basic information on how often to monitor certain aspects of health such as breast exams, pap smears, and how often and what types of vaccines children should receive. •

Be Wise, Immunize!: Vaccinate on Time Source: Cleveland, OH: Learning Curve of Weingart Design. 199x. [2 p.]. Contact: Available from Learning Curve of Weingart Design. 4614 Prospect Avenue, Number 421, Cleveland, OH 44103-4314. (800) 795-9295. Fax (216) 881-7177. Website: www.learningcurve1.com. PRICE: $10.00 for a pack of 100; single copies are not available. Summary: This oversized bookmark lists the latest recommendations for pediatric immunizations from the Centers for Disease Control (CDC). The bookmark reminds parents that getting the shots (vaccinations) and getting all of them, is one of the most important things they can do for their babies. The front of the bookmark lists the age and recommended immunizations. The reverse side lists each of the immunizations and briefly notes what each one covers. Included are vaccines against hepatitis B, which causes liver damage; Hib (haemophilus influenzae b), which causes brain infection and brain damage; DTP or DTaP, which protects against diphtheria (serious breathing problems that can lead to paralysis and heart failure), pertussis (whooping cough), and tetanus (causes painful muscle spasms leading to lockjaw); polio (OPV), a disease that can paralyze arms and legs; MMR, measles, mumps, and rubella (rubella is German measles, a more serious form of measles that can lead to birth defects in babies); and varicella, or chicken pox. The schedule printed on the front of the bookmark is recommended by the American Academy of Pediatrics and the American Academy of Family Physicians.

•

Lupus and Infections and Immunizations Source: Rockville, MD: Lupus Foundation of America, Inc. 1997. 6 p. Contact: Available from Lupus Foundation of America, Inc. 1300 Piccard Drive, Suite 200, Rockville, MD 20850-4303. (800) 558-0121 or (301) 670-9292. Website: www.lupus.org/lupus. PRICE: Available as part of a package of 21 different lupusrelated brochures for $3.95 plus shipping and handling. Summary: This pamphlet for people with lupus discusses the relationship of lupus to infections and immunizations. Lupus patients are more susceptible to infection than most other people because they have abnormalities in their immune systems that predispose them to develop infections. In addition, many of the drugs used to treat lupus, including cortisone-like drugs and cytotoxic drugs, suppress the function of the immune system. The pamphlet identifies types of infection in systemic lupus

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erythematosus (SLE), including infections caused by organisms that can induce infection in people with lupus and in the general population and infections caused by organisms capable of inducing disease when one's immune system is weakened. The most common infections among lupus patients are respiratory tract, skin, and urinary tract infections. Other topics include the clinical evaluation of possible infection through symptom evaluation and laboratory tests, the treatment and prevention of infection, and the possible adverse reactions of people with lupus to allergy shots and tetanus or flu vaccines. The pamphlet also provides information on the Lupus Foundation of America. •

Toma Buenas Decisiones: Tatuajes y Perforaciones del Cuerpo: Protegete de la Hepatitis y del VIH: Reduce tu Riesgo Contact: Journeyworks Publishing, PO Box 8466, Santa Cruz, CA, 95061-8466, (831) 4231400, http://www.promotehealth.com. Summary: This pamphlet presents information on the relationship between body art (tattoos and body piercing) and the transmission of human immunodeficiency virus (HIV)/acquired immune deficiency syndrome (AIDS), hepatitis B (HBV), hepatitis C (HCV), tuberculosis (TB), and tetanus. It discusses how unsterilized needles can lead to the transmission of these diseases and recommends that individuals consider the possible risks associated with body art, resist peer pressure to undergo such a procedure, and take steps to prevent HIV/hepatitis such as choosing a shop or artist that practices universal precautions.

•

Immunization dose counter. (2nd ed.) Source: Bryn Mawr, PA: Pennsylvania Chapter, American Academy of Pediatrics. 1994. 2 pp. Contact: Available from American Academy of Pediatrics, Pennsylvania Chapter, Dayton Building, Suite 220, 610 Old Lancaster Road, Bryn Mawr, PA 19010-3809. Telephone: (800) 243-2357 in Pennsylvania or (215) 520- 9125. $0.50. Summary: This pamphlet provides health care professionals or parents with guidelines on the schedule and types of vaccines which children should receive. These include diphtheria, tetanus and pertussis (DTP); polio; Haemophilus b conjugate (Hib); measles, mumps and rubella (MMR); and hepatitis B. Two recommended regimens of vaccines are given: for children whose first vaccination was given on time, and for those whose first vaccinations occurred late, i.e., later than one year of age. The content of this folder was reviewed by the Centers for Disease Control and the American Academy of Pediatrics.

•

Making Good Decisions: Tattoos and Body Piercing: Protecting Yourself From Hepatitis and HIV: Reducing Your Risk Contact: Journeyworks Publishing, PO Box 8466, Santa Cruz, CA, 95061-8466, (831) 4231400, http://www.promotehealth.com. Summary: This pamphlet, written for the general public, presents information on the relationship between body art (tattoos and body piercing) and the transmission of human immunodeficiency virus (HIV)/acquired immune deficiency syndrome (AIDS), hepatitis B (HBV), hepatitis C (HCV), tuberculosis (TB), and tetanus. It discusses how unsterilized needles can lead to the transmission of these diseases and recommends that individuals consider the possible risks associated with body art, resist peer pressure to undergo such a procedure, and take steps to prevent HIV/hepatitis (i.e., by visiting a

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body art professional who sterilizes the equipment, uses new disposable needles for each customer, and does not use a piercing gun). It recommends that customers ask their body art professional a list of questions before getting a tattoo or piercing. •

Immunizations: Not Just Kids' Stuff Source: St. Paul, MN: Immunization Action Coalition. 1997. 1 p. Contact: Available from Hepatitis B Coalition. 1573 Selby Avenue, Suite 229, St. Paul, MN 55104. (612) 647-9009. Fax (612) 647-9131. PRICE: $1.00. Summary: This reproducible brochure reviews some communicable diseases and the immunizations available to prevent them. The brochure reminds adult readers that getting immunized is a lifelong, life-protecting job. The brochure briefly describes each disease and then notes the vaccines and the recommendations for each. Included are: hepatitis B, MMR (measles, mumps, rubella), polio, Td (tetanus, diphtheria), varicella (chicken pox), hepatitis A, influenza vaccine (flu shot), and pneumococcal vaccine. The last page of the brochure features a blank immunization record and encourages readers to keep tract of their own immunization history. The brochure is illustrated with humorous line drawings.

•

Infection Control for the Dental Health Team Contact: Medcom Incorporated, PO Box 6003, Cypress, CA, (800) 541-0253. Summary: This teaching aid, consisting of a videorecording and an accompanying study guide, teaches users about infection-control in the dental practice. It consists of a course introduction, five lessons which include material from the study guide and an accompanying video segment, and a post-test. The lessons address the prevention of various diseases -- including the common cold, influenza, hepatitis B, syphilis, gonorrhea, rubella, mononucleosis, mumps, Acquired immunodeficiency syndrome (AIDS), herpes simplex, tuberculosis, and tetanus -- during dental procedures. The lessons look at handwashing, personal hygiene, the use of personal protective barriers, preventing cross-contamination, and disinfection and sterilization. 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: •

Age Page - Shots for Safety Summary: This fact sheet recommends immunization against influenza, pneumococcal diseases, tetanus, and diphtheria. A vaccine schedule and additional resources are included. Source: National Institute on Aging, National Institutes of Health http://www.healthfinder.gov/scripts/recordpass.asp?RecordType=0&RecordID=451

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•

Diphtheria, Tetanus, and Pertussis Vaccine Source: Immunization Action Coalition http://www.healthfinder.gov/scripts/recordpass.asp?RecordType=0&RecordID=7367

•

Tetanus and Diptheria Vaccine Source: Immunization Action Coalition http://www.healthfinder.gov/scripts/recordpass.asp?RecordType=0&RecordID=7374 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 tetanus. 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/

•

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 tetanus. By consulting all of associations listed in this chapter, you will have nearly exhausted all sources for patient associations concerned with tetanus.

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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 tetanus. 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 “tetanus” (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 “tetanus”. 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 “tetanus” (or synonyms) into the “For these words:” 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 “tetanus” (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.23

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

23

Adapted from the NLM: http://www.nlm.nih.gov/psd/cas/interlibrary.html.

224 Tetanus

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)24: •

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/

24

Abstracted from http://www.nlm.nih.gov/medlineplus/libraries.html.

Finding Medical Libraries

225

•

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

•

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

•

Illinois: Health Learning Center of Northwestern Memorial Hospital (Chicago), http://www.nmh.org/health_info/hlc.html

•

Illinois: Medical Library (OSF Saint Francis Medical Center, Peoria), http://www.osfsaintfrancis.org/general/library/

•

Kentucky: Medical Library - Services for Patients, Families, Students & the Public (Central Baptist Hospital, Lexington), http://www.centralbap.com/education/community/library.cfm

•

Kentucky: University of Kentucky - Health Information Library (Chandler Medical Center, Lexington), http://www.mc.uky.edu/PatientEd/

•

Louisiana: Alton Ochsner Medical Foundation Library (Alton Ochsner Medical Foundation, New Orleans), http://www.ochsner.org/library/

•

Louisiana: Louisiana State University Health Sciences Center Medical LibraryShreveport, http://lib-sh.lsuhsc.edu/

•

Maine: Franklin Memorial Hospital Medical Library (Franklin Memorial Hospital, Farmington), http://www.fchn.org/fmh/lib.htm

•

Maine: Gerrish-True Health Sciences Library (Central Maine Medical Center, Lewiston), http://www.cmmc.org/library/library.html

•

Maine: Hadley Parrot Health Science Library (Eastern Maine Healthcare, Bangor), http://www.emh.org/hll/hpl/guide.htm

•

Maine: Maine Medical Center Library (Maine Medical Center, Portland), http://www.mmc.org/library/

•

Maine: Parkview Hospital (Brunswick), http://www.parkviewhospital.org/

•

Maine: Southern Maine Medical Center Health Sciences Library (Southern Maine Medical Center, Biddeford), http://www.smmc.org/services/service.php3?choice=10

•

Maine: Stephens Memorial Hospital’s Health Information Library (Western Maine Health, Norway), http://www.wmhcc.org/Library/

226 Tetanus

•

Manitoba, Canada: Consumer & Patient Health Information Service (University of Manitoba Libraries), http://www.umanitoba.ca/libraries/units/health/reference/chis.html

•

Manitoba, Canada: J.W. Crane Memorial Library (Deer Lodge Centre, Winnipeg), http://www.deerlodge.mb.ca/crane_library/about.asp

•

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

•

Massachusetts: Baystate Medical Center Library (Baystate Health System), http://www.baystatehealth.com/1024/

•

Massachusetts: Boston University Medical Center Alumni Medical Library (Boston University Medical Center), http://med-libwww.bu.edu/library/lib.html

•

Massachusetts: Lowell General Hospital Health Sciences Library (Lowell General Hospital, Lowell), http://www.lowellgeneral.org/library/HomePageLinks/WWW.htm

•

Massachusetts: Paul E. Woodard Health Sciences Library (New England Baptist Hospital, Boston), http://www.nebh.org/health_lib.asp

•

Massachusetts: St. Luke’s Hospital Health Sciences Library (St. Luke’s Hospital, Southcoast Health System, New Bedford), http://www.southcoast.org/library/

•

Massachusetts: Treadwell Library Consumer Health Reference Center (Massachusetts General Hospital), http://www.mgh.harvard.edu/library/chrcindex.html

•

Massachusetts: UMass HealthNet (University of Massachusetts Medical School, Worchester), http://healthnet.umassmed.edu/

•

Michigan: Botsford General Hospital Library - Consumer Health (Botsford General Hospital, Library & Internet Services), http://www.botsfordlibrary.org/consumer.htm

•

Michigan: Helen DeRoy Medical Library (Providence Hospital and Medical Centers), http://www.providence-hospital.org/library/

•

Michigan: Marquette General Hospital - Consumer Health Library (Marquette General Hospital, Health Information Center), http://www.mgh.org/center.html

•

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

•

Michigan: Sladen Library & Center for Health Information Resources - Consumer Health Information (Detroit), http://www.henryford.com/body.cfm?id=39330

•

Montana: Center for Health Information (St. Patrick Hospital and Health Sciences Center, Missoula)

•

National: Consumer Health Library Directory (Medical Library Association, Consumer and Patient Health Information Section), http://caphis.mlanet.org/directory/index.html

•

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/

•

National: NN/LM List of Libraries Serving the Public (National Network of Libraries of Medicine), http://nnlm.gov/members/

Finding Medical Libraries

227

•

Nevada: Health Science Library, West Charleston Library (Las Vegas-Clark County Library District, Las Vegas), http://www.lvccld.org/special_collections/medical/index.htm

•

New Hampshire: Dartmouth Biomedical Libraries (Dartmouth College Library, Hanover), http://www.dartmouth.edu/~biomed/resources.htmld/conshealth.htmld/

•

New Jersey: Consumer Health Library (Rahway Hospital, Rahway), http://www.rahwayhospital.com/library.htm

•

New Jersey: Dr. Walter Phillips Health Sciences Library (Englewood Hospital and Medical Center, Englewood), http://www.englewoodhospital.com/links/index.htm

•

New Jersey: Meland Foundation (Englewood Hospital and Medical Center, Englewood), http://www.geocities.com/ResearchTriangle/9360/

•

New York: Choices in Health Information (New York Public Library) - NLM Consumer Pilot Project participant, http://www.nypl.org/branch/health/links.html

•

New York: Health Information Center (Upstate Medical University, State University of New York, Syracuse), http://www.upstate.edu/library/hic/

•

New York: Health Sciences Library (Long Island Jewish Medical Center, New Hyde Park), http://www.lij.edu/library/library.html

•

New York: ViaHealth Medical Library (Rochester General Hospital), http://www.nyam.org/library/

•

Ohio: Consumer Health Library (Akron General Medical Center, Medical & Consumer Health Library), http://www.akrongeneral.org/hwlibrary.htm

•

Oklahoma: The Health Information Center at Saint Francis Hospital (Saint Francis Health System, Tulsa), http://www.sfh-tulsa.com/services/healthinfo.asp

•

Oregon: Planetree Health Resource Center (Mid-Columbia Medical Center, The Dalles), http://www.mcmc.net/phrc/

•

Pennsylvania: Community Health Information Library (Milton S. Hershey Medical Center, Hershey), http://www.hmc.psu.edu/commhealth/

•

Pennsylvania: Community Health Resource Library (Geisinger Medical Center, Danville), http://www.geisinger.edu/education/commlib.shtml

•

Pennsylvania: HealthInfo Library (Moses Taylor Hospital, Scranton), http://www.mth.org/healthwellness.html

•

Pennsylvania: Hopwood Library (University of Pittsburgh, Health Sciences Library System, Pittsburgh), http://www.hsls.pitt.edu/guides/chi/hopwood/index_html

•

Pennsylvania: Koop Community Health Information Center (College of Physicians of Philadelphia), http://www.collphyphil.org/kooppg1.shtml

•

Pennsylvania: Learning Resources Center - Medical Library (Susquehanna Health System, Williamsport), http://www.shscares.org/services/lrc/index.asp

•

Pennsylvania: Medical Library (UPMC Health System, Pittsburgh), http://www.upmc.edu/passavant/library.htm

•

Quebec, Canada: Medical Library (Montreal General Hospital), http://www.mghlib.mcgill.ca/

228 Tetanus

•

South Dakota: Rapid City Regional Hospital Medical Library (Rapid City Regional Hospital), http://www.rcrh.org/Services/Library/Default.asp

•

Texas: Houston HealthWays (Houston Academy of Medicine-Texas Medical Center Library), http://hhw.library.tmc.edu/

•

Washington: Community Health Library (Kittitas Valley Community Hospital), http://www.kvch.com/

•

Washington: Southwest Washington Medical Center Library (Southwest Washington Medical Center, Vancouver), http://www.swmedicalcenter.com/body.cfm?id=72

229

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

•

Merriam-Webster Medical Dictionary (Inteli-Health, Inc.): http://www.intelihealth.com/IH/

•

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

•

On-line Medical Dictionary (CancerWEB): http://cancerweb.ncl.ac.uk/omd/

•

Rare Diseases Terms (Office of Rare Diseases): http://ord.aspensys.com/asp/diseases/diseases.asp

•

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). The NIH suggests the following Web sites in the ADAM Medical Encyclopedia when searching for information on tetanus: •

Basic Guidelines for Tetanus Tetanus Web site: http://www.nlm.nih.gov/medlineplus/ency/article/000615.htm Tetanus - vaccine Web site: http://www.nlm.nih.gov/medlineplus/ency/article/002031.htm

•

Signs & Symptoms for Tetanus Abdominal stiffness Web site: http://www.nlm.nih.gov/medlineplus/ency/article/003136.htm Airway obstruction Web site: http://www.nlm.nih.gov/medlineplus/ency/article/003075.htm Collapse Web site: http://www.nlm.nih.gov/medlineplus/ency/article/003092.htm

230 Tetanus

Constipation Web site: http://www.nlm.nih.gov/medlineplus/ency/article/003125.htm Convulsion Web site: http://www.nlm.nih.gov/medlineplus/ency/article/003200.htm Convulsions Web site: http://www.nlm.nih.gov/medlineplus/ency/article/003200.htm Cyanosis Web site: http://www.nlm.nih.gov/medlineplus/ency/article/003215.htm Difficulty breathing Web site: http://www.nlm.nih.gov/medlineplus/ency/article/003075.htm Drooling Web site: http://www.nlm.nih.gov/medlineplus/ency/article/003048.htm Dysphagia Web site: http://www.nlm.nih.gov/medlineplus/ency/article/003115.htm Fever Web site: http://www.nlm.nih.gov/medlineplus/ency/article/003090.htm Foot spasms Web site: http://www.nlm.nih.gov/medlineplus/ency/article/003194.htm Hand or foot spasms Web site: http://www.nlm.nih.gov/medlineplus/ency/article/003194.htm Hypotension Web site: http://www.nlm.nih.gov/medlineplus/ency/article/003083.htm Hypoxia Web site: http://www.nlm.nih.gov/medlineplus/ency/article/003215.htm Irritability Web site: http://www.nlm.nih.gov/medlineplus/ency/article/003214.htm Muscle Web site: http://www.nlm.nih.gov/medlineplus/ency/article/003193.htm Muscle contraction Web site: http://www.nlm.nih.gov/medlineplus/ency/article/003193.htm Muscle spasms Web site: http://www.nlm.nih.gov/medlineplus/ency/article/003193.htm Opisthotonos Web site: http://www.nlm.nih.gov/medlineplus/ency/article/003195.htm

Online Glossaries 231

Respiratory arrest Web site: http://www.nlm.nih.gov/medlineplus/ency/article/003069.htm Seizure Web site: http://www.nlm.nih.gov/medlineplus/ency/article/003200.htm Seizures Web site: http://www.nlm.nih.gov/medlineplus/ency/article/003200.htm Spasms Web site: http://www.nlm.nih.gov/medlineplus/ency/article/003193.htm Spasticity Web site: http://www.nlm.nih.gov/medlineplus/ency/article/003297.htm Stiffening of the neck and other muscles Web site: http://www.nlm.nih.gov/medlineplus/ency/article/003261.htm Swallowing difficulty Web site: http://www.nlm.nih.gov/medlineplus/ency/article/003115.htm Sweating, excessive Web site: http://www.nlm.nih.gov/medlineplus/ency/article/003218.htm Swelling Web site: http://www.nlm.nih.gov/medlineplus/ency/article/003103.htm Tachycardia Web site: http://www.nlm.nih.gov/medlineplus/ency/article/003077.htm Weakness Web site: http://www.nlm.nih.gov/medlineplus/ency/article/003174.htm •

Diagnostics and Tests for Tetanus ECT Web site: http://www.nlm.nih.gov/medlineplus/ency/article/003324.htm

•

Surgery and Procedures for Tetanus Tracheostomy Web site: http://www.nlm.nih.gov/medlineplus/ency/article/002955.htm

•

Background Topics for Tetanus Acute Web site: http://www.nlm.nih.gov/medlineplus/ency/article/002215.htm Allergic reaction Web site: http://www.nlm.nih.gov/medlineplus/ency/article/000005.htm

232 Tetanus

Antibodies Web site: http://www.nlm.nih.gov/medlineplus/ency/article/002223.htm Antibody Web site: http://www.nlm.nih.gov/medlineplus/ency/article/002223.htm Central nervous system Web site: http://www.nlm.nih.gov/medlineplus/ency/article/002311.htm Contraindications Web site: http://www.nlm.nih.gov/medlineplus/ency/article/002314.htm Diphtheria immunization (vaccine) Web site: http://www.nlm.nih.gov/medlineplus/ency/article/002018.htm DT vaccine Web site: http://www.nlm.nih.gov/medlineplus/ency/article/002021.htm Fractures Web site: http://www.nlm.nih.gov/medlineplus/ency/article/000001.htm Open wound Web site: http://www.nlm.nih.gov/medlineplus/ency/article/000043.htm Pacemaker Web site: http://www.nlm.nih.gov/medlineplus/ency/article/007070.htm Pertussis immunization (vaccine) Web site: http://www.nlm.nih.gov/medlineplus/ency/article/002027.htm Respiratory Web site: http://www.nlm.nih.gov/medlineplus/ency/article/002290.htm Shock Web site: http://www.nlm.nih.gov/medlineplus/ency/article/000039.htm Spores Web site: http://www.nlm.nih.gov/medlineplus/ency/article/002307.htm Td vaccine Web site: http://www.nlm.nih.gov/medlineplus/ency/article/002021.htm Tetanus immunization (vaccine) Web site: http://www.nlm.nih.gov/medlineplus/ency/article/002031.htm Wound Web site: http://www.nlm.nih.gov/medlineplus/ency/article/000043.htm Wounds Web site: http://www.nlm.nih.gov/medlineplus/ency/article/000043.htm

Online Glossaries 233

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

235

TETANUS DICTIONARY The definitions below are derived from official public sources, including the National Institutes of Health [NIH] and the European Union [EU]. 3-dimensional: 3-D. A graphic display of depth, width, and height. Three-dimensional radiation therapy uses computers to create a 3-dimensional picture of the tumor. This allows doctors to give the highest possible dose of radiation to the tumor, while sparing the normal tissue as much as possible. [NIH] 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] Ablation: The removal of an organ by surgery. [NIH] Acantholysis: Separation of the prickle cells of the stratum spinosum of the epidermis, resulting in atrophy of the prickle cell layer. It is seen in diseases such as pemphigus vulgaris (see pemphigus) and keratosis follicularis. [NIH] Acatalasia: A rare autosomal recessive disorder resulting from the absence of catalase activity. Though usually asymptomatic, a syndrome of oral ulcerations and gangrene may be present. [NIH] 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] Actin: Essential component of the cell skeleton. [NIH] Acute leukemia: A rapidly progressing cancer of the blood-forming tissue (bone marrow). [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] Acyclovir: Functional analog of the nucleoside guanosine. It acts as an antimetabolite, especially in viruses. It is used as an antiviral agent, especially in herpes infections. [NIH] Acyl: Chemical signal used by bacteria to communicate. [NIH] 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

236 Tetanus

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] Adenine: A purine base and a fundamental unit of adenine nucleotides. [NIH] Adenocarcinomas: A malignant tumor of the epithelial cells of a gland which typically metastasizes by way of the lymphatics. [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 Diphosphate: Adenosine 5'-(trihydrogen diphosphate). An adenine nucleotide containing two phosphate groups esterified to the sugar moiety at the 5'-position. [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 Cortex: The outer layer of the adrenal gland. It secretes mineralocorticoids, androgens, and glucocorticoids. [NIH] Adrenal Glands: Paired glands situated in the retroperitoneal tissues at the superior pole of each kidney. [NIH] 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] Adverse Effect: An unwanted side effect of treatment. [NIH] Aerobic: In biochemistry, reactions that need oxygen to happen or happen when oxygen is present. [NIH] Aerobic Exercise: A type of physical activity that includes walking, jogging, running, and dancing. Aerobic training improves the efficiency of the aerobic energy-producing systems that can improve cardiorespiratory endurance. [NIH] Aerosol: A solution of a drug which can be atomized into a fine mist for inhalation therapy. [EU]

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

Dictionary 237

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] 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]

Agarose: A polysaccharide complex, free of nitrogen and prepared from agar-agar which is produced by certain seaweeds (red algae). It dissolves in warm water to form a viscid solution. [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] Airway: A device for securing unobstructed passage of air into and out of the lungs during general anesthesia. [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] Algorithms: A procedure consisting of a sequence of algebraic formulas and/or logical steps to calculate or determine a given task. [NIH] Alimentary: Pertaining to food or nutritive material, or to the organs of digestion. [EU] Alkaline: Having the reactions of an alkali. [EU] Alkaloid: A member of a large group of chemicals that are made by plants and have nitrogen in them. Some alkaloids have been shown to work against cancer. [NIH] Alleles: Mutually exclusive forms of the same gene, occupying the same locus on homologous chromosomes, and governing the same biochemical and developmental process. [NIH] Allergen: An antigenic substance capable of producing immediate-type hypersensitivity (allergy). [EU] Allogeneic: Taken from different individuals of the same species. [NIH] Allylamine: Possesses an unusual and selective cytotoxicity for vascular smooth muscle cells in dogs and rats. Useful for experiments dealing with arterial injury, myocardial fibrosis or cardiac decompensation. [NIH] 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] 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

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herbal preparations; the drinking of special teas; and practices such as massage therapy, magnet therapy, spiritual healing, and meditation. [NIH] Alum: A type of immune adjuvant (a substance used to help boost the immune response to a vaccine). Also called aluminum sulfate. [NIH] Aluminum: A metallic element that has the atomic number 13, atomic symbol Al, and atomic weight 26.98. [NIH] Aluminum Compounds: Inorganic compounds that contain aluminum as an integral part of the molecule. [NIH] Aluminum Hydroxide: Hydrated aluminum. A compound with many biomedical applications: as a gastric antacid, an antiperspirant, in dentifrices, as an emulsifier, as an adjuvant in bacterins and vaccines, in water purification, etc. [NIH] Alveoli: Tiny air sacs at the end of the bronchioles in the lungs. [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] Ameliorating: A changeable condition which prevents the consequence of a failure or accident from becoming as bad as it otherwise would. [NIH] Amination: The creation of an amine. It can be produced by the addition of an amino group to an organic compound or reduction of a nitro group. [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 Motifs: Commonly observed structural components of proteins formed by simple combinations of adjacent secondary structures. A commonly observed structure may be composed of a conserved sequence which can be represented by a consensus sequence. [NIH]

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] 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]

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Amnion: The extraembryonic membrane which contains the embryo and amniotic fluid. [NIH]

Amphetamine: A powerful central nervous system stimulant and sympathomimetic. Amphetamine has multiple mechanisms of action including blocking uptake of adrenergics and dopamine, stimulation of release of monamines, and inhibiting monoamine oxidase. Amphetamine is also a drug of abuse and a psychotomimetic. The l- and the d,l-forms are included here. The l-form has less central nervous system activity but stronger cardiovascular effects. The d-form is dextroamphetamine. [NIH] Amyloid: A general term for a variety of different proteins that accumulate as extracellular fibrils of 7-10 nm and have common structural features, including a beta-pleated sheet conformation and the ability to bind such dyes as Congo red and thioflavine (Kandel, Schwartz, and Jessel, Principles of Neural Science, 3rd ed). [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] Analgesic: An agent that alleviates pain without causing loss of consciousness. [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] Analytes: A component of a test sample the presence of which has to be demonstrated. The term "analyte" includes where appropriate formed from the analyte during the analyses. [NIH]

Anaphylactic: Pertaining to anaphylaxis. [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] Anaphylaxis: An acute hypersensitivity reaction due to exposure to a previously encountered antigen. The reaction may include rapidly progressing urticaria, respiratory distress, vascular collapse, systemic shock, and death. [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] Anergy: Absence of immune response to particular substances. [NIH] Anesthesia: A state characterized by loss of feeling or sensation. This depression of nerve function is usually the result of pharmacologic action and is induced to allow performance of surgery or other painful procedures. [NIH] Anesthetics: Agents that are capable of inducing a total or partial loss of sensation, especially tactile sensation and pain. They may act to induce general anesthesia, in which an

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unconscious state is achieved, or may act locally to induce numbness or lack of sensation at a targeted site. [NIH] Angiotensin converting enzyme inhibitor: A drug used to decrease pressure inside blood vessels. [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 or other tissues are called xenograft models. [NIH] Anions: Negatively charged atoms, radicals or groups of atoms which travel to the anode or positive pole during electrolysis. [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]

Antibiotic Prophylaxis: Use of antibiotics before, during, or after a diagnostic, therapeutic, or surgical procedure to prevent infectious complications. [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] 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 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]

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Anti-Inflammatory Agents: Substances that reduce or suppress 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] 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] Antiseptic: A substance that inhibits the growth and development of microorganisms without necessarily killing them. [EU] 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] Antitoxin: A purified antiserum from animals (usually horses) immunized by injections of a toxin or toxoid, administered as a passive immunizing agent to neutralize a specific bacterial toxin, e.g., botulinus, tetanus or diphtheria. [EU] Antiviral: Destroying viruses or suppressing their replication. [EU] Anus: The opening of the rectum to the outside of the body. [NIH] Anxiety: Persistent feeling of dread, apprehension, and impending disaster. [NIH] Apnea: A transient absence of spontaneous respiration. [NIH] Applicability: A list of the commodities to which the candidate method can be applied as presented or with minor modifications. [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] 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] Aspartate: A synthetic amino acid. [NIH] Aspiration: The act of inhaling. [NIH] Aspirin: A drug that reduces pain, fever, inflammation, and blood clotting. Aspirin belongs to the family of drugs called nonsteroidal anti-inflammatory agents. It is also being studied in cancer prevention. [NIH] Assay: Determination of the amount of a particular constituent of a mixture, or of the biological or pharmacological potency of a drug. [EU] Astringents: Agents, usually topical, that cause the contraction of tissues for the control of bleeding or secretions. [NIH] Astrocytes: The largest and most numerous neuroglial cells in the brain and spinal cord. Astrocytes (from "star" cells) are irregularly shaped with many long processes, including

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those with "end feet" which form the glial (limiting) membrane and directly and indirectly contribute to the blood brain barrier. They regulate the extracellular ionic and chemical environment, and "reactive astrocytes" (along with microglia) respond to injury. Astrocytes have high- affinity transmitter uptake systems, voltage-dependent and transmitter-gated ion channels, and can release transmitter, but their role in signaling (as in many other functions) is not well understood. [NIH] Astrocytoma: A tumor that begins in the brain or spinal cord in small, star-shaped cells called astrocytes. [NIH] Atmospheric Pressure: The pressure at any point in an atmosphere due solely to the weight of the atmospheric gases above the point concerned. [NIH] Atopic: Pertaining to an atopen or to atopy; allergic. [EU] Atoxic: Not poisonous; not due to a poison. [EU] ATP: ATP an abbreviation for adenosine triphosphate, a compound which serves as a carrier of energy for cells. [NIH] Atresia: Lack of a normal opening from the esophagus, intestines, or anus. [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] Atropine: A toxic alkaloid, originally from Atropa belladonna, but found in other plants, mainly Solanaceae. [NIH] Attenuated: Strain with weakened or reduced virulence. [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 tumor cells: Cancer cells from an individual's own tumor. [NIH] Autonomic: Self-controlling; functionally independent. [EU] Autonomic Nervous System: The enteric, parasympathetic, and sympathetic nervous systems taken together. Generally speaking, the autonomic nervous system regulates the internal environment during both peaceful activity and physical or emotional stress. Autonomic activity is controlled and integrated by the central nervous system, especially the hypothalamus and the solitary nucleus, which receive information relayed from visceral afferents; these and related central and sensory structures are sometimes (but not here) considered to be part of the autonomic nervous system itself. [NIH] Autopsy: Postmortem examination of the body. [NIH] Avidity: The strength of the interaction of an antiserum with a multivalent antigen. [NIH] Axonal: Condition associated with metabolic derangement of the entire neuron and is

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manifest by degeneration of the distal portion of the nerve fiber. [NIH] Axons: Nerve fibers that are capable of rapidly conducting impulses away from the neuron cell body. [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] Baclofen: A GABA derivative that is a specific agonist at GABA-B receptors. It is used in the treatment of spasticity, especially that due to spinal cord damage. Its therapeutic effects result from actions at spinal and supraspinal sites, generally the reduction of excitatory transmission. [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 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] 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] 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 urine/microbiology for technical discussions on the isolation and segregation of bacteria in the urine. [NIH] Barium: An element of the alkaline earth group of metals. It has an atomic symbol Ba, atomic number 56, and atomic weight 138. All of its acid-soluble salts are poisonous. [NIH] Basal Ganglia: Large subcortical nuclear masses derived from the telencephalon and located in the basal regions of the cerebral hemispheres. [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] Basement Membrane: Ubiquitous supportive tissue adjacent to epithelium and around smooth and striated muscle cells. This tissue contains intrinsic macromolecular components such as collagen, laminin, and sulfated proteoglycans. As seen by light microscopy one of its subdivisions is the basal (basement) lamina. [NIH] Basophils: Granular leukocytes characterized by a relatively pale-staining, lobate nucleus

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and cytoplasm containing coarse dark-staining granules of variable size and stainable by basic dyes. [NIH] Belladonna: A species of very poisonous Solanaceous plants yielding atropine (hyoscyamine), scopolamine, and other belladonna alkaloids, used to block the muscarinic autonomic nervous system. [NIH] Benign: Not cancerous; does not invade nearby tissue or spread to other parts of the body. [NIH]

Beta-pleated: Particular three-dimensional pattern of amyloidoses. [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 Pigments: Pigments that give a characteristic color to bile including: bilirubin, biliverdine, and bilicyanin. [NIH] Biliary: Having to do with the liver, bile ducts, and/or gallbladder. [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] Bioassay: Determination of the relative effective strength of a substance (as a vitamin, hormone, or drug) by comparing its effect on a test organism with that of a standard preparation. [NIH] Bioavailability: The degree to which a drug or other substance becomes available to the target tissue after administration. [EU] Bioavailable: The ability of a drug or other substance to be absorbed and used by the body. Orally bioavailable means that a drug or other substance that is taken by mouth can be absorbed and used by the body. [NIH] Biochemical: Relating to biochemistry; characterized by, produced by, or involving chemical reactions in living organisms. [EU] Biogenic Amines: A group of naturally occurring amines derived by enzymatic decarboxylation of the natural amino acids. Many have powerful physiological effects (e.g., histamine, serotonin, epinephrine, tyramine). Those derived from aromatic amino acids, and also their synthetic analogs (e.g., amphetamine), are of use in pharmacology. [NIH] Biological Assay: A method of measuring the effects of a biologically active substance using an intermediate in vivo or in vitro tissue or cell model under controlled conditions. It includes virulence studies in animal fetuses in utero, mouse convulsion bioassay of insulin, quantitation of tumor-initiator systems in mouse skin, calculation of potentiating effects of a hormonal factor in an isolated strip of contracting stomach muscle, etc. [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] Biological Transport: The movement of materials (including biochemical substances and drugs) across cell membranes and epithelial layers, usually by passive diffusion. [NIH] Biomolecular: A scientific field at the interface between advanced computing and biotechnology. [NIH]

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Biopsy: Removal and pathologic examination of specimens in the form of small pieces of tissue from the living body. [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] Biotransformation: The chemical alteration of an exogenous substance by or in a biological system. The alteration may inactivate the compound or it may result in the production of an active metabolite of an inactive parent compound. The alteration may be either nonsynthetic (oxidation-reduction, hydrolysis) or synthetic (glucuronide formation, sulfate conjugation, acetylation, methylation). This also includes metabolic detoxication and clearance. [NIH] Biotype: A group of individuals having the same genotype. [NIH] Biphasic: Having two phases; having both a sporophytic and a gametophytic phase in the life cycle. [EU] 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] Blastocyst: The mammalian embryo in the post-morula stage in which a fluid-filled cavity, enclosed primarily by trophoblast, contains an inner cell mass which becomes the embryonic disc. [NIH] Blepharospasm: Excessive winking; tonic or clonic spasm of the orbicularis oculi muscle. [NIH]

Blister: Visible accumulations of fluid within or beneath the epidermis. [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 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] Blot: To transfer DNA, RNA, or proteins to an immobilizing matrix such as nitrocellulose. [NIH]

Body Fluids: Liquid components of living organisms. [NIH] Body Regions: Anatomical areas of the body. [NIH] Bone Marrow: The soft tissue filling the cavities of bones. Bone marrow exists in two types,

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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 Transplantation: The transference of bone marrow from one human or animal to another. [NIH] Bone scan: A technique to create images of bones on a computer screen or on film. A small amount of radioactive material is injected into a blood vessel and travels through the bloodstream; it collects in the bones and is detected by a scanner. [NIH] Botulinum Toxins: Toxins produced by Clostridium botulinum. There are at least seven different substances, most being proteins. They have neuro-, entero-, and hemotoxic properties, are immunogenic, and include the most potent poisons known. The most commonly used apparently blocks release of acetylcholine at cholinergic synapses. [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] Brachial Plexus: The large network of nerve fibers which distributes the innervation of the upper extremity. The brachial plexus extends from the neck into the axilla. In humans, the nerves of the plexus usually originate from the lower cervical and the first thoracic spinal cord segments (C5-C8 and T1), but variations are not uncommon. [NIH] Brain Hypoxia: Lack of oxygen leading to unconsciousness. [NIH] Brain Stem: The part of the brain that connects the cerebral hemispheres with the spinal cord. It consists of the mesencephalon, pons, and medulla oblongata. [NIH] Branch: Most commonly used for branches of nerves, but applied also to other structures. [NIH]

Breakdown: A physical, metal, or nervous collapse. [NIH] Breast Feeding: The nursing of an infant at the mother's breast. [NIH] Bronchi: The larger air passages of the lungs arising from the terminal bifurcation of the trachea. [NIH] Bronchial: Pertaining to one or more bronchi. [EU] Bronchiseptica: A small, gram-negative, motile bacillus. A normal inhabitant of the respiratory tract in man, dogs, and pigs, but is also associated with canine infectious tracheobronchitis and atrophic rhinitis in pigs. [NIH] Buccal: Pertaining to or directed toward the cheek. In dental anatomy, used to refer to the buccal surface of a tooth. [EU] Buffers: A chemical system that functions to control the levels of specific ions in solution. When the level of hydrogen ion in solution is controlled the system is called a pH buffer. [NIH]

Bupivacaine: A widely used local anesthetic agent. [NIH] Burns: Injuries to tissues caused by contact with heat, steam, chemicals (burns, chemical), electricity (burns, electric), or the like. [NIH] Burns, Electric: Burns produced by contact with electric current or from a sudden discharge of electricity. [NIH]

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Cadmium: An element with atomic symbol Cd, atomic number 48, and atomic weight 114. It is a metal and ingestion will lead to cadmium poisoning. [NIH] Cadmium Poisoning: Poisoning occurring after exposure to cadmium compounds or fumes. It may cause gastrointestinal syndromes, anemia, or pneumonitis. [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] Calcium Channels: Voltage-dependent cell membrane glycoproteins selectively permeable to calcium ions. They are categorized as L-, T-, N-, P-, Q-, and R-types based on the activation and inactivation kinetics, ion specificity, and sensitivity to drugs and toxins. The L- and T-types are present throughout the cardiovascular and central nervous systems and the N-, P-, Q-, & R-types are located in neuronal tissue. [NIH] Cancer vaccine: A vaccine designed to prevent or treat cancer. [NIH] Capsular: Cataract which is initiated by an opacification at the surface of the lens. [NIH] Capsules: Hard or soft soluble containers used for the oral administration of medicine. [NIH] Captopril: A potent and specific inhibitor of peptidyl-dipeptidase A. It blocks the conversion of angiotensin I to angiotensin II, a vasoconstrictor and important regulator of arterial blood pressure. Captopril acts to suppress the renin-angiotensin system and inhibits pressure responses to exogenous angiotensin. [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 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] Carboxy: Cannabinoid. [NIH] Carboxymethylcellulose: It is used as an emulsifier, thickener, suspending agent, etc., in cosmetics and pharmaceuticals; in research as a culture medium; in chromatography as a stabilizer for reagents; and therapeutically as a bulk laxative with antacid properties. [NIH] Carboxy-terminal: The end of any polypeptide or protein that bears a free carboxyl group. [NIH]

Carcinoembryonic Antigen: A glycoprotein that is secreted into the luminal surface of the epithelia in the gastrointestinal tract. It is found in the feces and pancreaticobiliary secretions and is used to monitor the respone to colon cancer treatment. [NIH] Carcinogenic: Producing carcinoma. [EU]

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Carcinogens: Substances that increase the risk of neoplasms in humans or animals. Both genotoxic chemicals, which affect DNA directly, and nongenotoxic chemicals, which induce neoplasms by other mechanism, are included. [NIH] 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] Cardiac Output: The volume of blood passing through the heart per unit of time. It is usually expressed as liters (volume) per minute so as not to be confused with stroke volume (volume per beat). [NIH] Cardiorespiratory: Relating to the heart and lungs and their function. [EU] Cardiovascular: Having to do with the heart and blood vessels. [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] Case series: A group or series of case reports involving patients who were given similar treatment. Reports of case series usually contain detailed information about the individual patients. This includes demographic information (for example, age, gender, ethnic origin) and information on diagnosis, treatment, response to treatment, and follow-up after treatment. [NIH] Castor Oil: Oil obtained from seeds of Ricinus communis that is used as a cathartic and as a plasticizer. [NIH] Catalase: An oxidoreductase that catalyzes the conversion of hydrogen peroxide to water and oxygen. It is present in many animal cells. A deficiency of this enzyme results in acatalasia. EC 1.11.1.6. [NIH] Catalyse: To speed up a chemical reaction. [EU] Catecholamine: A group of chemical substances manufactured by the adrenal medulla and secreted during physiological stress. [NIH] Cathode: An electrode, usually an incandescent filament of tungsten, which emits electrons in an X-ray tube. [NIH] Cations: Postively charged atoms, radicals or groups of atoms which travel to the cathode or negative pole during electrolysis. [NIH] Caudate Nucleus: Elongated gray mass of the neostriatum located adjacent to the lateral ventricle of the brain. [NIH] Caveolae: Endocytic/exocytic cell membrane structures rich in glycosphingolipids, cholesterol, and lipid-anchored membrane proteins that function in endocytosis (potocytosis), transcytosis, and signal transduction. Caveolae assume various shapes from open pits to closed vesicles. Caveolar coats are composed of caveolins. [NIH] Caveolins: The main structural proteins of caveolae. Several distinct genes for caveolins have been identified. [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 Adhesion: Adherence of cells to surfaces or to other cells. [NIH]

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Cell Count: A count of the number of cells of a specific kind, usually measured per unit volume of sample. [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] Cell Division: The fission of a cell. [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 Membrane Structures: Structures which are part of the cell membrane or have cell membrane as a major part of their structure. [NIH] Cell Physiology: Characteristics and physiological processes of cells from cell division to cell death. [NIH] 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] Cell Transplantation: Transference of cells within an individual, between individuals of the same species, or between individuals of different species. [NIH] Cellular Structures: Components of a cell. [NIH] Central Nervous System: The main information-processing organs of the nervous system, consisting of the brain, spinal cord, and meninges. [NIH] Centrifugation: A method of separating organelles or large molecules that relies upon differential sedimentation through a preformed density gradient under the influence of a gravitational field generated in a centrifuge. [NIH] Cerebral: Of or pertaining of the cerebrum or the brain. [EU] Cerebral hemispheres: The two halves of the cerebrum, the part of the brain that controls muscle functions of the body and also controls speech, emotions, reading, writing, and learning. The right hemisphere controls muscle movement on the left side of the body, and the left hemisphere controls muscle movement on the right side of the body. [NIH] Cerebral Palsy: Refers to a motor disability caused by a brain dysfunction. [NIH] 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]

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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] Character: In current usage, approximately equivalent to personality. The sum of the relatively fixed personality traits and habitual modes of response of an individual. [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] Chemotherapeutics: Noun plural but singular or plural in constructions : chemotherapy. [EU]

Chemotherapy: Treatment with anticancer drugs. [NIH] Chickenpox: A mild, highly contagious virus characterized by itchy blisters all over the body. [NIH] Child Care: Care of children in the home or institution. [NIH] Chimeras: Organism that contains a mixture of genetically different cells. [NIH] Chimeric Proteins: Proteins in individuals that are derived from genetically different zygotes. [NIH] Chlorhexidine: Disinfectant and topical anti-infective agent used also as mouthwash to prevent oral plaque. [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 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] Choline: A basic constituent of lecithin that is found in many plants and animal organs. It is important as a precursor of acetylcholine, as a methyl donor in various metabolic processes, and in lipid metabolism. [NIH] Cholinergic: Resembling acetylcholine in pharmacological action; stimulated by or releasing acetylcholine or a related compound. [EU] Chorioamnionitis: An inflammatory process involving the chorion, its fetal blood vessels, the umbilical cord, and the amnion by extension of the inflammation, as the amnion itself has no blood supply. This inflammatory process is potentially fatal to mother and fetus.

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[NIH]

Chorion: The outermost extraembryonic membrane. [NIH] Choroid: The thin, highly vascular membrane covering most of the posterior of the eye between the retina and sclera. [NIH] Chromaffin Cells: Cells that store epinephrine secretory vesicles. During times of stress, the nervous system signals the vesicles to secrete their hormonal content. Their name derives from their ability to stain a brownish color with chromic salts. Characteristically, they are located in the adrenal medulla and paraganglia (paraganglia, chromaffin) of the sympathetic nervous system. [NIH] Chromaffin Granules: Granules in the adrenal glands and various other organs, which are concerned with the synthesis, storage, metabolism, and secretion of epinephrine and norepinephrine. [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] Chromic: Catgut sterilized and impregnated with chromium trioxide. [NIH] Chromium: A trace element that plays a role in glucose metabolism. It has the atomic symbol Cr, atomic number 24, and atomic weight 52. According to the Fourth Annual Report on Carcinogens (NTP85-002,1985), chromium and some of its compounds have been listed as known carcinogens. [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] Chronic: A disease or condition that persists or progresses over a long period of time. [NIH] Chronic prostatitis: Inflammation of the prostate gland, developing slowly and lasting a long time. [NIH] Chymopapain: A cysteine endopeptidase isolated from papaya latex. Preferential cleavage at glutamic and aspartic acid residues. EC 3.4.22.6. [NIH] Circadian: Repeated more or less daily, i. e. on a 23- to 25-hour cycle. [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] Clamp: A u-shaped steel rod used with a pin or wire for skeletal traction in the treatment of certain fractures. [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]

Clinical study: A research study in which patients receive treatment in a clinic or other medical facility. Reports of clinical studies can contain results for single patients (case reports) or many patients (case series or clinical trials). [NIH] 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]

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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]

Clonic: Pertaining to or of the nature of clonus. [EU] 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] Clot Retraction: Retraction of a clot resulting from contraction of platelet pseudopods attached to fibrin strands that is dependent on the contractile protein thrombosthenin. Used as a measure of platelet function. [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] Coca: Any of several South American shrubs of the Erythroxylon genus (and family) that yield cocaine; the leaves are chewed with alum for CNS stimulation. [NIH] Cocaine: An alkaloid ester extracted from the leaves of plants including coca. It is a local anesthetic and vasoconstrictor and is clinically used for that purpose, particularly in the eye, ear, nose, and throat. It also has powerful central nervous system effects similar to the amphetamines and is a drug of abuse. Cocaine, like amphetamines, acts by multiple mechanisms on brain catecholaminergic neurons; the mechanism of its reinforcing effects is thought to involve inhibition of dopamine uptake. [NIH] Cod Liver Oil: Oil obtained from fresh livers of the cod family, Gadidae. It is a source of vitamins A and D. [NIH] Cofactor: A substance, microorganism or environmental factor that activates or enhances the action of another entity such as a disease-causing agent. [NIH] Cognition: Intellectual or mental process whereby an organism becomes aware of or obtains knowledge. [NIH] Colic: Paroxysms of pain. This condition usually occurs in the abdominal region but may occur in other body regions as well. [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] 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] Colonoscopy: Endoscopic examination, therapy or surgery of the luminal surface of the colon. [NIH] Colorectal: Having to do with the colon or the rectum. [NIH]

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Combinatorial: A cut-and-paste process that churns out thousands of potentially valuable compounds at once. [NIH] Communicable disease: A disease that can be transmitted by contact between persons. [NIH] Communis: Common tendon of the rectus group of muscles that surrounds the optic foramen and a portion of the superior orbital fissure, to the anterior margin of which it is attached at the spina recti lateralis. [NIH] 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] Complement Activation: The sequential activation of serum components C1 through C9, initiated by an erythrocyte-antibody complex or by microbial polysaccharides and properdin, and producing an inflammatory response. [NIH] 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] 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] Computed tomography: CT scan. A series of detailed pictures of areas inside the body, taken from different angles; the pictures are created by a computer linked to an x-ray machine. Also called computerized tomography and computerized axial tomography (CAT)

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scan. [NIH] Computerized axial tomography: A series of detailed pictures of areas inside the body, taken from different angles; the pictures are created by a computer linked to an x-ray machine. Also called CAT scan, computed tomography (CT scan), or computerized tomography. [NIH] Conception: The onset of pregnancy, marked by implantation of the blastocyst; the formation of a viable zygote. [EU] Concomitant: Accompanying; accessory; joined with another. [EU] Cones: One type of specialized light-sensitive cells (photoreceptors) in the retina that provide sharp central vision and color vision. [NIH] 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] Conjunctiva: The mucous membrane that lines the inner surface of the eyelids and the anterior part of the sclera. [NIH] Conjunctivitis: Inflammation of the conjunctiva, generally consisting of conjunctival hyperaemia associated with a discharge. [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] Consensus Sequence: A theoretical representative nucleotide or amino acid sequence in which each nucleotide or amino acid is the one which occurs most frequently at that site in the different sequences which occur in nature. The phrase also refers to an actual sequence which approximates the theoretical consensus. A known conserved sequence set is represented by a consensus sequence. Commonly observed supersecondary protein structures (amino acid motifs) are often formed by conserved sequences. [NIH] Conserved Sequence: A sequence of amino acids in a polypeptide or of nucleotides in DNA or RNA that is similar across multiple species. A known set of conserved sequences is represented by a consensus sequence. Amino acid motifs are often composed of conserved sequences. [NIH] Consultation: A deliberation between two or more physicians concerning the diagnosis and the proper method of treatment in a case. [NIH] Consumption: Pulmonary tuberculosis. [NIH] Contamination: The soiling or pollution by inferior material, as by the introduction of

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organisms into a wound, or sewage into a stream. [EU] Contraceptive: An agent that diminishes the likelihood of or prevents conception. [EU] Contracture: A condition of fixed high resistance to passive stretch of a muscle, resulting from fibrosis of the tissues supporting the muscles or the joints, or from disorders of the muscle fibres. [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] Contralateral: Having to do with the opposite side of the body. [NIH] Contrast Media: Substances used in radiography that allow visualization of certain tissues. [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] Controlled study: An experiment or clinical trial that includes a comparison (control) group. [NIH]

Convulsion: A violent involuntary contraction or series of contractions of the voluntary muscles. [EU] Convulsive: Relating or referring to spasm; affected with spasm; characterized by a spasm or spasms. [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] Cornea: The transparent part of the eye that covers the iris and the pupil and allows light to enter the inside. [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 Thrombosis: Presence of a thrombus in a coronary artery, often causing a myocardial infarction. [NIH] Corpus: The body of the uterus. [NIH] Corpus Striatum: Striped gray and white matter consisting of the neostriatum and paleostriatum (globus pallidus). It is located in front of and lateral to the thalamus in each cerebral hemisphere. The gray substance is made up of the caudate nucleus and the lentiform nucleus (the latter consisting of the globus pallidus and putamen). The white matter is the internal capsule. [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] Corticosteroids: Hormones that have antitumor activity in lymphomas and lymphoid leukemias; in addition, corticosteroids (steroids) may be used for hormone replacement and for the management of some of the complications of cancer and its treatment. [NIH] Cortisol: A steroid hormone secreted by the adrenal cortex as part of the body's response to stress. [NIH] Cortisone: A natural steroid hormone produced in the adrenal gland. It can also be made in the laboratory. Cortisone reduces swelling and can suppress immune responses. [NIH] Cranial: Pertaining to the cranium, or to the anterior (in animals) or superior (in humans)

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end of the body. [EU] Cranial Nerve Injuries: Dysfunction of one or more cranial nerves causally related to a traumatic injury. Penetrating and nonpenetrating craniocerebral trauma; neck injuries; and trauma to the facial region are conditions associated with cranial nerve injuries. [NIH] Cranial Nerves: Twelve pairs of nerves that carry general afferent, visceral afferent, special afferent, somatic efferent, and autonomic efferent fibers. [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] Creatine: An amino acid that occurs in vertebrate tissues and in urine. In muscle tissue, creatine generally occurs as phosphocreatine. Creatine is excreted as creatinine in the urine. [NIH]

Creatinine: A compound that is excreted from the body in urine. Creatinine levels are measured to monitor kidney function. [NIH] Crotoxin: A specific complex of toxic proteins from the venom of Crotalus durissus terrificus (South American rattlesnake). It can be separated into a phospholipase A and crotapotin fragment; the latter consists of three different amino acid chains, potentiates the enzyme, and is specifically neurotoxic. [NIH] Crystallization: The formation of crystals; conversion to a crystalline form. [EU] Curare: Plant extracts from several species, including Strychnos toxifera, S. castelnaei, S. crevauxii, and Chondodendron tomentosum, that produce paralysis of skeletal muscle and are used adjunctively with general anesthesia. These extracts are toxic and must be used with the administration of artificial respiration. [NIH] Curative: Tending to overcome disease and promote recovery. [EU] Cutaneous: Having to do with the skin. [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] 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]

Cytokine: Small but highly potent protein that modulates the activity of many cell types, including T and B cells. [NIH] Cytomegalovirus: A genus of the family Herpesviridae, subfamily Betaherpesvirinae, infecting the salivary glands, liver, spleen, lungs, eyes, and other organs, in which they produce characteristically enlarged cells with intranuclear inclusions. Infection with Cytomegalovirus is also seen as an opportunistic infection in AIDS. [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] Cytotoxic: Cell-killing. [NIH] Cytotoxicity: Quality of being capable of producing a specific toxic action upon cells of special organs. [NIH] Data Display: The visual display of data in a man-machine system. An example is a cathode ray tube display in which certain data can be called for from the computer and presented on

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the screen. [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]

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] Decidua: The epithelial lining of the endometrium that is formed before the fertilized ovum reaches the uterus. The fertilized ovum embeds in the decidua. If the ovum is not fertilized, the decidua is shed during menstruation. [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] Dehydroepiandrosterone: DHEA. A substance that is being studied as a cancer prevention drug. It belongs to the family of drugs called steroids. [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] 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]

Dendritic cell vaccine: A vaccine made of antigens and dendritic antigen-presenting cells (APCs). [NIH] Density: The logarithm to the base 10 of the opacity of an exposed and processed film. [NIH] Dental Caries: Localized destruction of the tooth surface initiated by decalcification of the enamel followed by enzymatic lysis of organic structures and leading to cavity formation. If left unchecked, the cavity may penetrate the enamel and dentin and reach the pulp. The three most prominent theories used to explain the etiology of the disase are that acids produced by bacteria lead to decalcification; that micro-organisms destroy the enamel protein; or that keratolytic micro-organisms produce chelates that lead to decalcification. [NIH]

Dentate Gyrus: Gray matter situated above the gyrus hippocampi. It is composed of three layers. The molecular layer is continuous with the hippocampus in the hippocampal fissure. The granular layer consists of closely arranged spherical or oval neurons, called granule

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cells, whose axons pass through the polymorphic layer ending on the dendrites of pyramidal cells in the hippocampus. [NIH] Dentifrices: Any preparations used for cleansing teeth; they usually contain an abrasive, detergent, binder and flavoring agent and may exist in the form of liquid, paste or powder; may also contain medicaments and caries preventives. [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] Dermatitis: Any inflammation of the skin. [NIH] Dermatomycoses: Superficial infections of the skin or its appendages by any of various fungi. [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] Detergents: Purifying or cleansing agents, usually salts of long-chain aliphatic bases or acids, that exert cleansing (oil-dissolving) and antimicrobial effects through a surface action that depends on possessing both hydrophilic and hydrophobic properties. [NIH] 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] Dextrans: A group of glucose polymers made by certain bacteria. Dextrans are used therapeutically as plasma volume expanders and anticoagulants. They are also commonly used in biological experimentation and in industry for a wide variety of purposes. [NIH] Diabetes Insipidus: A metabolic disorder due to disorders in the production or release of vasopressin. It is characterized by the chronic excretion of large amounts of low specific gravity urine and great thirst. [NIH] Diabetes Mellitus: A heterogeneous group of disorders that share glucose intolerance in common. [NIH] Diabetic Foot: Ulcers of the foot as a complication of diabetes. Diabetic foot, often with infection, is a common serious complication of diabetes and may require hospitalization and disfiguring surgery. The foot ulcers are probably secondary to neuropathies and vascular problems. [NIH] Diagnostic procedure: A method used to identify a disease. [NIH] Dialyzer: A part of the hemodialysis machine. (See hemodialysis under dialysis.) The dialyzer has two sections separated by a membrane. One section holds dialysate. The other holds the patient's blood. [NIH] Diamines: Organic chemicals which have two amino groups in an aliphatic chain. [NIH] Diarrhea: Passage of excessively liquid or excessively frequent stools. [NIH]

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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] Digitonin: A glycoside obtained from Digitalis purpurea; the aglycone is digitogenin which is bound to five sugars. Digitonin solubilizes lipids, especially in membranes and is used as a tool in cellular biochemistry, and reagent for precipitating cholesterol. It has no cardiac effects. [NIH] Dilatation: The act of dilating. [NIH] Dilution: A diluted or attenuated medicine; in homeopathy, the diffusion of a given quantity of a medicinal agent in ten or one hundred times the same quantity of water. [NIH] Dimethyl: A volatile metabolite of the amino acid methionine. [NIH] Diphtheria: A localized infection of mucous membranes or skin caused by toxigenic strains of Corynebacterium diphtheriae. It is characterized by the presence of a pseudomembrane at the site of infection. Diphtheria toxin, produced by C. diphtheriae, can cause myocarditis, polyneuritis, and other systemic toxic effects. [NIH] Diphtheria Toxin: A 60 kD single chain protein elaborated by Corynebacterium diphtheriae that causes the sign and symptoms of diphtheria; it can be broken into two unequal fragments, the smaller (A fragment) inhibits protein synthesis and is the lethal moiety that needs the larger (B fragment) for entry into cells. [NIH] Diphtheria-Tetanus Vaccine: A combined vaccine used to prevent infection with diphtheria and tetanus toxoid. This is used in place of DTP vaccine (diphtheria-tetanus-pertussis vaccine) when pertussis vaccine is contraindicated. [NIH] Diphtheria-Tetanus-acellular Pertussis Vaccines: Combined vaccines consisting of diphtheria toxoid, tetanus toxoid, and an acellular form of pertussis vaccine. At least five different purifed antigens of B. pertussis have been used in various combinations in these vaccines. [NIH] Diphtheria-Tetanus-Pertussis Vaccine: A vaccine consisting of diphtheria toxoid, tetanus toxoid, and whole-cell pertussis vaccine. The vaccine protects against diphtheria, tetanus, and whooping cough. [NIH] Direct: 1. Straight; in a straight line. 2. Performed immediately and without the intervention of subsidiary means. [EU] Disease Progression: The worsening of a disease over time. This concept is most often used for chronic and incurable diseases where the stage of the disease is an important determinant of therapy and prognosis. [NIH] Disinfectant: An agent that disinfects; applied particularly to agents used on inanimate objects. [EU] Disinfection: Rendering pathogens harmless through the use of heat, antiseptics, antibacterial agents, etc. [NIH] Dissociation: 1. The act of separating or state of being separated. 2. The separation of a

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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] Distal: Remote; farther from any point of reference; opposed to proximal. In dentistry, used to designate a position on the dental arch farther from the median line of the jaw. [EU] Disulphide: 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] Diuresis: Increased excretion of urine. [EU] Diuretic: A drug that increases the production of urine. [NIH] Diurnal: Occurring during the day. [EU] DNA Topoisomerase: An enzyme catalyzing ATP-independent breakage of single-stranded DNA, followed by passage and rejoining of another single-stranded DNA. This enzyme class brings about the conversion of one topological isomer of DNA into another, e.g., the relaxation of superhelical turns in DNA, the interconversion of simple and knotted rings of single-stranded DNA, and the intertwisting of single-stranded rings of complementary sequences. (From Enzyme Nomenclature, 1992) EC 5.99.1.2. [NIH] Dopamine: An endogenous catecholamine and prominent neurotransmitter in several 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] Drive: A state of internal activity of an organism that is a necessary condition before a given stimulus will elicit a class of responses; e.g., a certain level of hunger (drive) must be present before food will elicit an eating response. [NIH] Drug Interactions: The action of a drug that may affect the activity, metabolism, or toxicity of another drug. [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] 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

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may or may not be permanent. Dyes can also be used as therapeutic agents and test reagents in medicine and scientific research. [NIH] Dynorphins: A class of opioid peptides including dynorphin A, dynorphin B, and smaller fragments of these peptides. Dynorphins prefer kappa-opioid receptors (receptors, opioid, kappa) and have been shown to play a role as central nervous system transmitters. [NIH] Dyskinesias: Abnormal involuntary movements which primarily affect the extremities, trunk, or jaw that occur as a manifestation of an underlying disease process. Conditions which feature recurrent or persistent episodes of dyskinesia as a primary manifestation of disease may be referred to as dyskinesia syndromes (movement disorders). Dyskinesias are also a relatively common manifestation of basal ganglia diseases. [NIH] Dysphagia: Difficulty in swallowing. [EU] Dysphonia: Difficulty or pain in speaking; impairment of the voice. [NIH] Dyspnea: Difficult or labored breathing. [NIH] Dystonia: Disordered tonicity of muscle. [EU] Eating Disorders: A group of disorders characterized by physiological and psychological disturbances in appetite or food intake. [NIH] Eczema: A pruritic papulovesicular dermatitis occurring as a reaction to many endogenous and exogenous agents (Dorland, 27th ed). [NIH] 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] Ejaculation: The release of semen through the penis during orgasm. [NIH] Elastin: The protein that gives flexibility to tissues. [NIH] Electrocoagulation: Electrosurgical procedures used to treat hemorrhage (e.g., bleeding ulcers) and to ablate tumors, mucosal lesions, and refractory arrhythmias. [NIH] Electrode: Component of the pacing system which is at the distal end of the lead. It is the interface with living cardiac tissue across which the stimulus is transmitted. [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]

Electrophysiological: Pertaining to electrophysiology, that is a branch of physiology that is concerned with the electric phenomena associated with living bodies and involved in their

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functional activity. [EU] Electroshock: Induction of a stress reaction in experimental subjects by means of an electrical shock; applies to either convulsive or non-convulsive states. [NIH] Elementary Particles: Individual components of atoms, usually subatomic; subnuclear particles are usually detected only when the atomic nucleus decays and then only transiently, as most of them are unstable, often yielding pure energy without substance, i.e., radiation. [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] Enamel: A very hard whitish substance which covers the dentine of the anatomical crown of a tooth. [NIH] Encapsulated: Confined to a specific, localized area and surrounded by a thin layer of tissue. [NIH]

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] Encephalitis, Viral: Inflammation of brain parenchymal tissue as a result of viral infection. Encephalitis may occur as primary or secondary manifestation of Togaviridae infections; Herpesviridae infections; Adenoviridae infections; Flaviviridae infections; Bunyaviridae infections; Picornaviridae infections; Paramyxoviridae infections; Orthomyxoviridae infections; Retroviridae infections; and Arenaviridae infections. [NIH] Encephalomyelitis: A general term indicating inflammation of the brain and spinal cord, often used to indicate an infectious process, but also applicable to a variety of autoimmune and toxic-metabolic conditions. There is significant overlap regarding the usage of this term and encephalitis in the literature. [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] Endocardium: The innermost layer of the heart, comprised of endothelial cells. [NIH] Endocytosis: Cellular uptake of extracellular materials within membrane-limited vacuoles or microvesicles. Endosomes play a central role in endocytosis. [NIH] Endometrium: The layer of tissue that lines the uterus. [NIH]

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Endopeptidases: A subclass of peptide hydrolases. They are classified primarily by their catalytic mechanism. Specificity is used only for identification of individual enzymes. They comprise the serine endopeptidases, EC 3.4.21; cysteine endopeptidases, EC 3.4.22; aspartic endopeptidases, EC 3.4.23, metalloendopeptidases, EC 3.4.24; and a group of enzymes yet to be assigned to any of the above sub-classes, EC 3.4.99. EC 3.4.-. [NIH] Endorphins: One of the three major groups of endogenous opioid peptides. They are large peptides derived from the pro-opiomelanocortin precursor. The known members of this group are alpha-, beta-, and gamma-endorphin. The term endorphin is also sometimes used to refer to all opioid peptides, but the narrower sense is used here; opioid peptides is used for the broader group. [NIH] Endothelial cell: The main type of cell found in the inside lining of blood vessels, lymph vessels, and the heart. [NIH] Endotoxin: Toxin from cell walls of bacteria. [NIH] Enkephalin: A natural opiate painkiller, in the hypothalamus. [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] Enterocolitis: Inflammation of the intestinal mucosa of the small and large bowel. [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] Entorhinal Cortex: Cortex where the signals are combined with those from other sensory systems. [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]

Environmental Pollutants: Substances which pollute the environment. Use environmental pollutants in general or for which there is no specific heading. [NIH]

for

Enzymatic: Phase where enzyme cuts the precursor protein. [NIH] Enzyme: A protein that speeds up chemical reactions in the body. [NIH] Enzyme-Linked Immunosorbent Assay: An immunoassay utilizing an antibody labeled with an enzyme marker such as horseradish peroxidase. While either the enzyme or the antibody is bound to an immunosorbent substrate, they both retain their biologic activity; the change in enzyme activity as a result of the enzyme-antibody-antigen reaction is proportional to the concentration of the antigen and can be measured spectrophotometrically or with the naked eye. Many variations of the method have been developed. [NIH] Eosinophilic: A condition found primarily in grinding workers caused by a reaction of the pulmonary tissue, in particular the eosinophilic cells, to dust that has entered the lung. [NIH] Eosinophilic Gastroenteritis: Infection and swelling of the lining of the stomach, small intestine, or large intestine. The infection is caused by white blood cells (eosinophils). [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]

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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] Epidermoid carcinoma: A type of cancer in which the cells are flat and look like fish scales. Also called squamous cell carcinoma. [NIH] Epidural: The space between the wall of the spinal canal and the covering of the spinal cord. An epidural injection is given into this space. [NIH] Epiglottis: Thin leaf-shaped cartilage, covered with mucous membrane, at the root of the tongue, which folds back over the entrance to the larynx, covering it, during the act of swallowing. [NIH] Epiglottitis: Inflammation of the epiglottis. [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]

Erectile: The inability to get or maintain an erection for satisfactory sexual intercourse. Also called impotence. [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] Erythrasma: A chronic bacterial infection of major folds of the skin, caused by Corynebacterium minutissimum. [NIH] Erythrocytes: Red blood cells. Mature erythrocytes are non-nucleated, biconcave disks

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containing hemoglobin whose function is to transport oxygen. [NIH] Esophagus: The muscular tube through which food passes from the throat to the stomach. [NIH]

Esotropia: A form of ocular misalignment characterized by an excessive convergence of the visual axes, resulting in a "cross-eye" appearance. An example of this condition occurs when paralysis of the lateral rectus muscle causes an abnormal inward deviation of one eye on attempted gaze. [NIH] Estrogens: A class of sex hormones associated with the development and maintenance of secondary female sex characteristics and control of the cyclical changes in the reproductive cycle. They are also required for pregnancy maintenance and have an anabolic effect on protein metabolism and water retention. [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] Ethnic Groups: A group of people with a common cultural heritage that sets them apart from others in a variety of social relationships. [NIH] Evoke: The electric response recorded from the cerebral cortex after stimulation of a peripheral sense organ. [NIH] Excitation: An act of irritation or stimulation or of responding to a stimulus; the addition of energy, as the excitation of a molecule by absorption of photons. [EU] Excitatory: When cortical neurons are excited, their output increases and each new input they receive while they are still excited raises their output markedly. [NIH] Excitotoxicity: Excessive exposure to glutamate or related compounds can kill brain neurons, presumably by overstimulating them. [NIH] Exhaustion: The feeling of weariness of mind and body. [NIH] Exocytosis: Cellular release of material within membrane-limited vesicles by fusion of the vesicles with the cell membrane. [NIH] Exogenous: Developed or originating outside the organism, as exogenous disease. [EU] Exotoxin: Toxic substance excreted by living bacterial cells. [NIH] Exotropia: A form of ocular misalignment where the visual axes diverge inappropriately. For example, medial rectus muscle weakness may produce this condition as the affected eye will deviate laterally upon attempted forward gaze. An exotropia occurs due to the relatively unopposed force exerted on the eye by the lateral rectus muscle, which pulls the eye in an outward direction. [NIH] Expiration: The act of breathing out, or expelling air from the lungs. [EU] External radiation: Radiation therapy that uses a machine to aim high-energy rays at the cancer. Also called external-beam radiation. [NIH] Extracellular: Outside a cell or cells. [EU] 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 Space: Interstitial space between cells, occupied by fluid as well as amorphous and fibrous substances. [NIH]

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Extraction: The process or act of pulling or drawing out. [EU] Extrapyramidal: Outside of the pyramidal tracts. [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] Facial: Of or pertaining to the face. [EU] Facial Pain: Pain in the facial region including orofacial pain and craniofacial pain. Associated conditions include local inflammatory and neoplastic disorders and neuralgic syndromes involving the trigeminal, facial, and glossopharyngeal nerves. Conditions which feature recurrent or persistent facial pain as the primary manifestation of disease are referred to as facial pain syndromes. [NIH] 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] Fatal Outcome: Death resulting from the presence of a disease in an individual, as shown by a single case report or a limited number of patients. This should be differentiated from death, the physiological cessation of life and from mortality, an epidemiological or statistical concept. [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] Febrile: Pertaining to or characterized by fever. [EU] 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] Fetal Blood: Blood of the fetus. Exchange of nutrients and waste between the fetal and maternal blood occurs via the placenta. The cord blood is blood contained in the umbilical vessels at the time of delivery. [NIH] Fetus: The developing offspring from 7 to 8 weeks after conception until birth. [NIH] Fever of Unknown Origin: Fever in which the etiology cannot be ascertained. [NIH] Fibrin: A protein derived from fibrinogen in the presence of thrombin, which forms part of the blood clot. [NIH] Fibroblasts: Connective tissue cells which secrete an extracellular matrix rich in collagen and other macromolecules. [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] Firearms: Small-arms weapons, including handguns, pistols, revolvers, rifles, shotguns, etc.

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[NIH]

Fissure: Any cleft or groove, normal or otherwise; especially a deep fold in the cerebral cortex which involves the entire thickness of the brain wall. [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] Flaccid: Weak, lax and soft. [EU] Flow Cytometry: Technique using an instrument system for making, processing, and displaying one or more measurements on individual cells obtained from a cell suspension. Cells are usually stained with one or more fluorescent dyes specific to cell components of interest, e.g., DNA, and fluorescence of each cell is measured as it rapidly transverses the excitation beam (laser or mercury arc lamp). Fluorescence provides a quantitative measure of various biochemical and biophysical properties of the cell, as well as a basis for cell sorting. Other measurable optical parameters include light absorption and light scattering, the latter being applicable to the measurement of cell size, shape, density, granularity, and stain uptake. [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 Dyes: Dyes that emit light when exposed to light. The wave length of the emitted light is usually longer than that of the incident light. Fluorochromes are substances that cause fluorescence in other substances, i.e., dyes used to mark or label other compounds with fluorescent tags. They are used as markers in biochemistry and immunology. [NIH] Foetal: Of or pertaining to a fetus; pertaining to in utero development after the embryonic period. [EU] Fold: A plication or doubling of various parts of the body. [NIH] Follicles: Shafts through which hair grows. [NIH] Folliculitis: Inflammation of follicles, primarily hair follicles. [NIH] Food Hypersensitivity: Gastrointestinal disturbances, skin eruptions, or shock due to allergic reactions to allergens ingested in food. [NIH] Food Packaging: Containers, packaging, and packaging materials for processed and raw foods and beverages. It includes packaging intended to be used for storage and also used for preparation of foods such as microwave food containers versus cooking and eating utensils. Packaging materials may be intended for food contact or designated non-contact, for example, shipping containers. Food labeling is also available. [NIH]

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Foot Ulcer: Lesion on the surface of the skin of the foot, usually accompanied by inflammation. The lesion may become infected or necrotic and is frequently associated with diabetes or leprosy. [NIH] Forearm: The part between the elbow and the wrist. [NIH] Fractionation: Dividing the total dose of radiation therapy into several smaller, equal doses delivered over a period of several days. [NIH] 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] Gallbladder: The pear-shaped organ that sits below the liver. Bile is concentrated and stored in the gallbladder. [NIH] Ganglia: Clusters of multipolar neurons surrounded by a capsule of loosely organized connective tissue located outside the central nervous system. [NIH] Ganglion: 1. A knot, or knotlike mass. 2. A general term for a group of nerve cell bodies located outside the central nervous system; occasionally applied to certain nuclear groups within the brain or spinal cord, e.g. basal ganglia. 3. A benign cystic tumour occurring on a aponeurosis or tendon, as in the wrist or dorsum of the foot; it consists of a thin fibrous capsule enclosing a clear mucinous fluid. [EU] Ganglioside: Protein kinase C's inhibitor which reduces ischemia-related brain damage. [NIH]

Gangrene: Death and putrefaction of tissue usually due to a loss of blood supply. [NIH] Gangrenous: A circumscribed, deep-seated, suppurative inflammation of the subcutaneous tissue of the eyelid discharging pus from several points. [NIH] Gap Junctions: Connections between cells which allow passage of small molecules and electric current. Gap junctions were first described anatomically as regions of close apposition between cells with a narrow (1-2 nm) gap between cell membranes. The variety in the properties of gap junctions is reflected in the number of connexins, the family of proteins which form the junctions. [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 exchange: Primary function of the lungs; transfer of oxygen from inhaled air into the blood and of carbon dioxide from the blood into the lungs. [NIH] Gastric: Having to do with the stomach. [NIH] Gastric Juices: Liquids produced in the stomach to help break down food and kill bacteria. [NIH]

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Gastric Mucosa: Surface epithelium in the stomach that invaginates into the lamina propria, forming gastric pits. Tubular glands, characteristic of each region of the stomach (cardiac, gastric, and pyloric), empty into the gastric pits. The gastric mucosa is made up of several different kinds of cells. [NIH] Gastrin: A hormone released after eating. Gastrin causes the stomach to produce more acid. [NIH]

Gastritis: Inflammation of the stomach. [EU] 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 Fusion: Fusion of structural genes to analyze protein behavior or fusion of regulatory sequences with structural genes to determine mechanisms of regulation. [NIH] General practitioner: A medical practitioner who does not specialize in a particular branch of medicine or limit his practice to a specific class of diseases. [NIH] Generator: Any system incorporating a fixed parent radionuclide from which is produced a daughter radionuclide which is to be removed by elution or by any other method and used in a radiopharmaceutical. [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] Genetics: The biological science that deals with the phenomena and mechanisms of heredity. [NIH] Genistein: An isoflavonoid derived from soy products. It inhibits protein-tyrosine kinase and topoisomerase-ii (dna topoisomerase (atp-hydrolysing)) activity and is used as an antineoplastic and antitumor agent. Experimentally, it has been shown to induce G2 phase arrest in human and murine cell lines. [NIH] Genital: Pertaining to the genitalia. [EU] Genotype: The genetic constitution of the individual; the characterization of the genes. [NIH] Geriatric: Pertaining to the treatment of the aged. [EU] Germ Cells: The reproductive cells in multicellular organisms. [NIH] Germinal Center: The activated center of a lymphoid follicle in secondary lymphoid tissue

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where B-lymphocytes are stimulated by antigens and helper T cells (T-lymphocytes, helperinducer) are stimulated to generate memory cells. [NIH] Gestation: The period of development of the young in viviparous animals, from the time of fertilization of the ovum until birth. [EU] 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] Glioblastoma: A malignant form of astrocytoma histologically characterized by pleomorphism of cells, nuclear atypia, microhemorrhage, and necrosis. They may arise in any region of the central nervous system, with a predilection for the cerebral hemispheres, basal ganglia, and commissural pathways. Clinical presentation most frequently occurs in the fifth or sixth decade of life with focal neurologic signs or seizures. [NIH] Glioblastoma multiforme: A type of brain tumor that forms from glial (supportive) tissue of the brain. It grows very quickly and has cells that look very different from normal cells. Also called grade IV astrocytoma. [NIH] Gliosis: The production of a dense fibrous network of neuroglia; includes astrocytosis, which is a proliferation of astrocytes in the area of a degenerative lesion. [NIH] Globus Pallidus: The representation of the phylogenetically oldest part of the corpus striatum called the paleostriatum. It forms the smaller, more medial part of the lentiform nucleus. [NIH] Glomerular: Pertaining to or of the nature of a glomerulus, especially a renal glomerulus. [EU]

Glomerular Filtration Rate: The volume of water filtered out of plasma through glomerular capillary walls into Bowman's capsules per unit of time. It is considered to be equivalent to inulin clearance. [NIH] 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] Glomerulus: A tiny set of looping blood vessels in the nephron where blood is filtered in the kidney. [NIH] Glossopharyngeal Nerve: The 9th cranial nerve. The glossopharyngeal nerve is a mixed motor and sensory nerve; it conveys somatic and autonomic efferents as well as general, special, and visceral afferents. Among the connections are motor fibers to the stylopharyngeus muscle, parasympathetic fibers to the parotid glands, general and taste afferents from the posterior third of the tongue, the nasopharynx, and the palate, and afferents from baroreceptors and chemoreceptors of the carotid sinus. [NIH] Glottis: The vocal apparatus of the larynx, consisting of the true vocal cords (plica vocalis) and the opening between them (rima glottidis). [NIH] Glucans: Polysaccharides composed of repeating glucose units. They can consist of branched or unbranched chains in any linkages. [NIH] Glucocorticoid: A compound that belongs to the family of compounds called corticosteroids (steroids). Glucocorticoids affect metabolism and have anti-inflammatory and immunosuppressive effects. They may be naturally produced (hormones) or synthetic (drugs). [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

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therapeutically in fluid and nutrient replacement. [NIH] Glucose Intolerance: A pathological state in which the fasting plasma glucose level is less than 140 mg per deciliter and the 30-, 60-, or 90-minute plasma glucose concentration following a glucose tolerance test exceeds 200 mg per deciliter. This condition is seen frequently in diabetes mellitus but also occurs with other diseases. [NIH] Glucosyltransferases: Enzymes that catalyze the transfer of glucose from a nucleoside diphosphate glucose to an acceptor molecule which is frequently another carbohydrate. EC 2.4.1.-. [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] 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]

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] Glycols: A generic grouping for dihydric alcohols with the hydroxy groups (-OH) located on different carbon atoms. They are viscous liquids with high boiling points for their molecular weights. [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] Glycosylation: The chemical or biochemical addition of carbohydrate or glycosyl groups to other chemicals, especially peptides or proteins. Glycosyl transferases are used in this biochemical reaction. [NIH] Gonadal: Pertaining to a gonad. [EU] Gonadotropic: Stimulating the gonads; applied to hormones of the anterior pituitary which influence the gonads. [EU] Gonadotropin: The water-soluble follicle stimulating substance, by some believed to originate in chorionic tissue, obtained from the serum of pregnant mares. It is used to supplement the action of estrogens. [NIH] Gonads: The gamete-producing glands, ovary or testis. [NIH] Gonorrhea: Acute infectious disease characterized by primary invasion of the urogenital tract. The etiologic agent, Neisseria gonorrhoeae, was isolated by Neisser in 1879. [NIH] 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]

Grade: The grade of a tumor depends on how abnormal the cancer cells look under a

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microscope and how quickly the tumor is likely to grow and spread. Grading systems are different for each type of cancer. [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] Grafting: The operation of transfer of tissue from one site to another. [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-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] Granule: A small pill made from sucrose. [EU] Granulocytes: Leukocytes with abundant granules in the cytoplasm. They are divided into three groups: neutrophils, eosinophils, and basophils. [NIH] Granulomas: Small lumps in tissues caused by inflammation. [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] 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] Habitual: Of the nature of a habit; according to habit; established by or repeated by force of habit, customary. [EU] Haemophilus: A genus of Pasteurellaceae that consists of several species occurring in animals and humans. Its organisms are described as gram-negative, facultatively anaerobic, coccobacillus or rod-shaped, and nonmotile. [NIH] Haemophilus influenzae: A species of Haemophilus found on the mucous membranes of humans and a variety of animals. The species is further divided into biotypes I through VIII. [NIH]

Haemophilus influenzae type b: A type of H. influenzae isolated most frequently from biotype I. Prior to vaccine availability, it was a leading cause of childhood meningitis. [NIH] Hair follicles: Shafts or openings on the surface of the skin through which hair grows. [NIH] Half-Life: The time it takes for a substance (drug, radioactive nuclide, or other) to lose half of its pharmacologic, physiologic, or radiologic activity. [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] 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

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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] Health Behavior: Behaviors expressed by individuals to protect, maintain or promote their health status. For example, proper diet, and appropriate exercise are activities perceived to influence health status. Life style is closely associated with health behavior and factors influencing life style are socioeconomic, educational, and cultural. [NIH] Health Promotion: Encouraging consumer behaviors most likely to optimize health potentials (physical and psychosocial) through health information, preventive programs, and access to medical care. [NIH] Health Status: The level of health of the individual, group, or population as subjectively assessed by the individual or by more objective measures. [NIH] Heart failure: Loss of pumping ability by the heart, often accompanied by fatigue, breathlessness, and excess fluid accumulation in body tissues. [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] 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] 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] Hemorrhage: Bleeding or escape of blood from a vessel. [NIH] Hemostasis: The process which spontaneously arrests the flow of blood from vessels carrying blood under pressure. It is accomplished by contraction of the vessels, adhesion and aggregation of formed blood elements, and the process of blood or plasma coagulation. [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] Hepatobiliary: Pertaining to the liver and the bile or the biliary ducts. [EU] Hepatocytes: The main structural component of the liver. They are specialized epithelial cells that are organized into interconnected plates called lobules. [NIH]

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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 Zoster: Acute vesicular inflammation. [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]

Heterogenic: Derived from a different source or species. Also called heterogenous. [NIH] Heterogenous: Derived from a different source or species. Also called heterogenic. [NIH] Heterotrophic: Pertaining to organisms that are consumers and dependent on other organisms for their source of energy (food). [NIH] Heterotropia: One in which the angle of squint remains relatively unaltered on conjugate movement of the eyes. [NIH] Hippocampus: A curved elevation of gray matter extending the entire length of the floor of the temporal horn of the lateral ventricle (Dorland, 28th ed). The hippocampus, subiculum, and dentate gyrus constitute the hippocampal formation. Sometimes authors include the entorhinal cortex in the hippocampal formation. [NIH] 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] 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] Homozygote: An individual in which both alleles at a given locus are identical. [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] Hormone Replacement Therapy: Therapeutic use of hormones to alleviate the effects of hormone deficiency. [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] Hospitals, Public: Hospitals controlled by various types of government, i.e., city, county, district, state or federal. [NIH]

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Host: Any animal that receives a transplanted graft. [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] Hybridoma: A hybrid cell resulting from the fusion of a specific antibody-producing spleen cell with a myeloma cell. [NIH] Hydrochloric Acid: A strong corrosive acid that is commonly used as a laboratory reagent. It is formed by dissolving hydrogen chloride in water. Gastric acid is the hydrochloric acid component of gastric juice. [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] 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] Hydroxides: Inorganic compounds that contain the OH- group. [NIH] Hydroxyl Radical: The univalent radical OH that is present in hydroxides, alcohols, phenols, glycols. [NIH] Hydroxylamine: A colorless inorganic compound (HONH2) used in organic synthesis and as a reducing agent, due to its ability to donate nitric oxide. [NIH] Hydroxylysine: A hydroxylated derivative of the amino acid lysine that is present in certain collagens. [NIH] Hydroxyproline: A hydroxylated form of the imino acid proline. A deficiency in ascorbic acid can result in impaired hydroxyproline formation. [NIH] Hygienic: Pertaining to hygiene, or conducive to health. [EU] Hyperaemia: An excess of blood in a part; engorgement. [EU] Hyperbaric: Characterized by greater than normal pressure or weight; applied to gases under greater than atmospheric pressure, as hyperbaric oxygen, or to a solution of greater specific gravity than another taken as a standard of reference. [EU] Hyperbaric oxygen: Oxygen that is at an atmospheric pressure higher than the pressure at

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sea level. Breathing hyperbaric oxygen to enhance the effectiveness of radiation therapy is being studied. [NIH] Hyperbilirubinemia: Pathologic process consisting of an abnormal increase in the amount of bilirubin in the circulating blood, which may result in jaundice. [NIH] Hyperhidrosis: Excessive sweating. In the localized type, the most frequent sites are the palms, soles, axillae, inguinal folds, and the perineal area. Its chief cause is thought to be emotional. Generalized hyperhidrosis may be induced by a hot, humid environment, by fever, or by vigorous exercise. [NIH] Hypersensitivity: Altered reactivity to an antigen, which can result in pathologic reactions upon subsequent exposure to that particular antigen. [NIH] Hypoglycemia: Abnormally low blood sugar [NIH] Hypoglycemic: An orally active drug that produces a fall in blood glucose concentration. [NIH]

Hypotension: Abnormally low blood pressure. [NIH] Hypothalamic: Of or involving the hypothalamus. [EU] Hypothalamus: Ventral part of the diencephalon extending from the region of the optic chiasm to the caudal border of the mammillary bodies and forming the inferior and lateral walls of the third ventricle. [NIH] Hypothermia: Lower than normal body temperature, especially in warm-blooded animals; in man usually accidental or unintentional. [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] Imaging procedures: Methods of producing pictures of areas inside the body. [NIH] Immune adjuvant: A drug that stimulates the immune system to respond to disease. [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). [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] 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] Immunization Programs: Organized services to administer immunization procedures in the prevention of various diseases. The programs are made available over a wide range of sites: schools, hospitals, public health agencies, voluntary health agencies, etc. They are administered to an equally wide range of population groups or on various administrative levels: community, municipal, state, national, international. [NIH]

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Immunization Schedule: Schedule giving optimum times usually for primary and/or secondary immunization. [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] Immunochemistry: Field of chemistry that pertains to immunological phenomena and the study of chemical reactions related to antigen stimulation of tissues. It includes physicochemical interactions between antigens and antibodies. [NIH] Immunocompromised: Having a weakened immune system caused by certain diseases or treatments. [NIH] Immunocompromised Host: A human or animal whose immunologic mechanism is deficient because of an immunodeficiency disorder or other disease or as the result of the administration of immunosuppressive drugs or radiation. [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]

Immunogen: A substance that is capable of causing antibody formation. [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] Immunologic Memory: The altered state of immunologic responsiveness resulting from initial contact with antigen, which enables the individual to produce antibodies more rapidly and in greater quantity in response to secondary antigenic stimulus. [NIH] Immunologic Tests: Diagnostic techniques involving the demonstration or measurement of an immune response, including antibody production or assay, antigen-antibody reactions, serologic cross-reactivity, delayed hypersensitivity reactions, or heterogenetic responses. [NIH]

Immunology: The study of the body's immune system. [NIH] Immunomodulator: New type of drugs mainly using biotechnological methods. Treatment of cancer. [NIH] Immunophenotyping: Process of classifying cells of the immune system based on structural and functional differences. The process is commonly used to analyze and sort Tlymphocytes into subsets based on CD antigens by the technique of flow cytometry. [NIH] 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] 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

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commonly located on the face, especially about the mouth and nose. [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] 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] Indomethacin: A non-steroidal anti-inflammatory agent (NSAID) that inhibits the enzyme cyclooxygenase necessary for the formation of prostaglandins and other autacoids. It also inhibits the motility of polymorphonuclear leukocytes. [NIH] 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] Infancy: The period of complete dependency prior to the acquisition of competence in walking, talking, and self-feeding. [NIH] Infant Mortality: Perinatal, neonatal, and infant deaths in a given population. [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 Mononucleosis: A common, acute infection usually caused by the Epstein-Barr virus (Human herpesvirus 4). There is an increase in mononuclear white blood cells and other atypical lymphocytes, generalized lymphadenopathy, splenomegaly, and occasionally hepatomegaly with hepatitis. [NIH] Infertility: The diminished or absent ability to conceive or produce an offspring while sterility is the complete inability to conceive or produce an offspring. [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.

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[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] Infusion: A method of putting fluids, including drugs, into the bloodstream. Also called intravenous infusion. [NIH] Ingestion: Taking into the body by mouth [NIH] Inguinal: Pertaining to the inguen, or groin. [EU] Inhalation: The drawing of air or other substances into the lungs. [EU] 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] Inlay: In dentistry, a filling first made to correspond with the form of a dental cavity and then cemented into the cavity. [NIH] Inner ear: The labyrinth, comprising the vestibule, cochlea, and semicircular canals. [NIH] Innervation: 1. The distribution or supply of nerves to a part. 2. The supply of nervous energy or of nerve stimulus sent to a part. [EU] Inorganic: Pertaining to substances not of organic origin. [EU] Inositol: An isomer of glucose that has traditionally been considered to be a B vitamin although it has an uncertain status as a vitamin and a deficiency syndrome has not been identified in man. (From Martindale, The Extra Pharmacopoeia, 30th ed, p1379) Inositol phospholipids are important in signal transduction. [NIH] Inotropic: Affecting the force or energy of muscular contractions. [EU] 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] 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] Intensive Care: Advanced and highly specialized care provided to medical or surgical patients whose conditions are life-threatening and require comprehensive care and constant monitoring. It is usually administered in specially equipped units of a health care facility. [NIH]

Interferon: A biological response modifier (a substance that can improve the body's natural 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

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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-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] Internal Capsule: White matter pathway, flanked by nuclear masses, consisting of both afferent and efferent fibers projecting between the cerebral cortex and the brainstem. It consists of three distinct parts: an anterior limb, posterior limb, and genu. [NIH] Interneurons: Most generally any neurons which are not motor or sensory. Interneurons may also refer to neurons whose axons remain within a particular brain region as contrasted with projection neurons which have axons projecting to other brain regions. [NIH] Interstitial: Pertaining to or situated between parts or in the interspaces of a tissue. [EU] Intestinal: Having to do with 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] Intoxication: Poisoning, the state of being poisoned. [EU] Intracellular: Inside a cell. [NIH] Intracellular Membranes: Membranes of subcellular structures. [NIH] Intramuscular: IM. Within or into muscle. [NIH] Intramuscular injection: IM. Injection into a muscle. [NIH] Intrathecal: Describes the fluid-filled space between the thin layers of tissue that cover the brain and spinal cord. Drugs can be injected into the fluid or a sample of the fluid can be removed for testing. [NIH] Intravenous: IV. Into a vein. [NIH] Intrinsic: Situated entirely within or pertaining exclusively to a part. [EU] Inulin: A starch found in the tubers and roots of many plants. Since it is hydrolyzable to fructose, it is classified as a fructosan. It has been used in physiologic investigation for determination of the rate of glomerular function. [NIH] Invalidate: To weaken or make valueless : to discredit. [EU] 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 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] 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]

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Ipsilateral: Having to do with the same side of the body. [NIH] Ischemia: Deficiency of blood in a part, due to functional constriction or actual obstruction of a blood vessel. [EU] 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 Focusing: Electrophoresis in which a pH gradient is established in a gel medium and proteins migrate until they reach the site (or focus) at which the pH is equal to their isoelectric point. [NIH] Isoelectric Point: The pH in solutions of proteins and related compounds at which the dipolar ions are at a maximum. [NIH] Jaundice: A clinical manifestation of hyperbilirubinemia, consisting of deposition of bile pigments in the skin, resulting in a yellowish staining of the skin and mucous membranes. [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] Keratolytic: An agent that promotes keratolysis. [EU] Keto: It consists of 8 carbon atoms and within the endotoxins, it connects poysaccharide and lipid A. [NIH] Keyhole: A carrier molecule. [NIH] Keyhole limpet hemocyanin: KLH. One of a group of drugs called immune modulators, given as a vaccine to help the body respond to cancer. [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 Transplantation: The transference of a kidney from one human or animal to another. [NIH] Killer Cells: Lymphocyte-like effector cells which mediate antibody-dependent cell cytotoxicity. They kill antibody-coated target cells which they bind with their Fc receptors. [NIH]

Kinetic: Pertaining to or producing motion. [EU] Labile: 1. Gliding; moving from point to point over the surface; unstable; fluctuating. 2. Chemically unstable. [EU] Laceration: 1. The act of tearing. 2. A torn, ragged, mangled wound. [EU] Lactose Intolerance: The disease state resulting from the absence of lactase enzyme in the musocal cells of the gastrointestinal tract, and therefore an inability to break down the disaccharide lactose in milk for absorption from the gastrointestinal tract. It is manifested by indigestion of a mild nature to severe diarrhea. It may be due to inborn defect genetically conditioned or may be acquired. [NIH] Lanthanum: The prototypical element in the rare earth family of metals. It has the atomic symbol La, atomic number 57, and atomic weight 138.91. Lanthanide ion is used in experimental biology as a calcium antagonist; lanthanum oxide improves the optical

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properties of glass. [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] Laryngeal: Having to do with the larynx. [NIH] Larynx: An irregularly shaped, musculocartilaginous tubular structure, lined with mucous membrane, located at the top of the trachea and below the root of the tongue and the hyoid bone. It is the essential sphincter guarding the entrance into the trachea and functioning secondarily as the organ of voice. [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. [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] Lesion: An area of abnormal tissue change. [NIH] Lethal: Deadly, fatal. [EU] Leucocyte: All the white cells of the blood and their precursors (myeloid cell series, lymphoid cell series) but commonly used to indicate granulocytes exclusive of lymphocytes. [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] Libido: The psychic drive or energy associated with sexual instinct in the broad sense (pleasure and love-object seeking). It may also connote the psychic energy associated with instincts in general that motivate behavior. [NIH] Library Services: Services offered to the library user. They include reference and circulation. [NIH]

Lidocaine: A local anesthetic and cardiac depressant used as an antiarrhythmia agent. Its actions are more intense and its effects more prolonged than those of procaine but its duration of action is shorter than that of bupivacaine or prilocaine. [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]

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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] Lipophilic: Having an affinity for fat; pertaining to or characterized by lipophilia. [EU] 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 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] Liposomes: Artificial, single or multilaminar vesicles (made from lecithins or other lipids) that are used for the delivery of a variety of biological molecules or molecular complexes to cells, for example, drug delivery and gene transfer. They are also used to study membranes and membrane proteins. [NIH] 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] Liver: A large, glandular organ located in the upper abdomen. The liver cleanses the blood and aids in digestion by secreting bile. [NIH] Liver cancer: A disease in which malignant (cancer) cells are found in the tissues of the liver. [NIH]

Liver scan: An image of the liver created on a computer screen or on film. A radioactive substance is injected into a blood vessel and travels through the bloodstream. It collects in the liver, especially in abnormal areas, and can be detected by the scanner. [NIH] Liver Transplantation: The transference of a part of or an entire liver from one human or animal to another. [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] Lockjaw: Inability to open the mouth due to tonic contracture of the muscles of the jaw. [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] Locomotor: Of or pertaining to locomotion; pertaining to or affecting the locomotive apparatus of the body. [EU] Longitudinal Studies: Studies in which variables relating to an individual or group of individuals are assessed over a period of time. [NIH] Long-Term Care: Care over an extended period, usually for a chronic condition or disability, requiring periodic, intermittent, or continuous care. [NIH] Long-Term Potentiation: A persistent increase in synaptic efficacy, usually induced by

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appropriate activation of the same synapses. The phenomenological properties of long-term potentiation suggest that it may be a cellular mechanism of learning and memory. [NIH] Lumen: The cavity or channel within a tube or tubular organ. [EU] Lupus: A form of cutaneous tuberculosis. It is seen predominantly in women and typically involves the nasal, buccal, and conjunctival mucosa. [NIH] 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]

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] 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] Lymphocytic: Referring to lymphocytes, a type of white blood cell. [NIH] Lymphocytosis: Excess of normal lymphocytes in the blood or in any effusion. [NIH] Lymphoid: Referring to lymphocytes, a type of white blood cell. Also refers to tissue in which lymphocytes develop. [NIH] Lysine: An essential amino acid. It is often added to animal feed. [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] Magnetic Resonance Imaging: Non-invasive method of demonstrating internal anatomy based on the principle that atomic nuclei in a strong magnetic field absorb pulses of radiofrequency energy and emit them as radiowaves which can be reconstructed into computerized images. The concept includes proton spin tomographic techniques. [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] 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 characterized by irregularly recurring febrile paroxysms that in extreme cases occur with

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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] Malignancy: A cancerous tumor that can invade and destroy nearby tissue and spread to other parts of the body. [NIH] Malignant: Cancerous; a growth with a tendency to invade and destroy nearby tissue and spread to other parts of the body. [NIH] Malignant tumor: A tumor capable of metastasizing. [NIH] Malnutrition: A condition caused by not eating enough food or not eating a balanced diet. [NIH]

Mammogram: An x-ray of the breast. [NIH] Mammography: Radiographic examination of the breast. [NIH] Manifest: Being the part or aspect of a phenomenon that is directly observable : concretely expressed in behaviour. [EU] Mannitol: A diuretic and renal diagnostic aid related to sorbitol. It has little significant energy value as it is largely eliminated from the body before any metabolism can take place. It can be used to treat oliguria associated with kidney failure or other manifestations of inadequate renal function and has been used for determination of glomerular filtration rate. Mannitol is also commonly used as a research tool in cell biological studies, usually to control osmolarity. [NIH] Masseter Muscle: A masticatory muscle whose action is closing the jaws. [NIH] Mastication: The act and process of chewing and grinding food in the mouth. [NIH] Mastitis: Inflammatory disease of the breast, or mammary gland. [NIH] Mastocyte: A mast cell. [EU] Maxillofacial Injuries: General or unspecified injuries involving the face and jaw (either upper, lower, or both). [NIH] Measles Virus: The type species of morbillivirus and the cause of the highly infectious human disease measles, which affects mostly children. [NIH] Measles-Mumps-Rubella Vaccine: A combined vaccine used to prevent measles, mumps, and rubella. [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]

Medial: Lying near the midsaggital plane of the body; opposed to lateral. [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] Medical Records: Recording of pertinent information concerning patient's illness or illnesses. [NIH] MEDLINE: An online database of MEDLARS, the computerized bibliographic Medical Literature Analysis and Retrieval System of the National Library of Medicine. [NIH]

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Medullary: Pertaining to the marrow or to any medulla; resembling marrow. [EU] 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] Melanoma vaccine: A cancer vaccine prepared from human melanoma cancer cells. It can be used alone or with other therapy in treating melanoma. [NIH] Membrane: A very thin layer of tissue that covers a surface. [NIH] Membrane Fusion: The adherence of cell membranes, intracellular membranes, or artifical membrane models of either to each other or to viruses, parasites, or interstitial particles through a variety of chemical and physical processes. [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] Memory: Complex mental function having four distinct phases: (1) memorizing or learning, (2) retention, (3) recall, and (4) recognition. Clinically, it is usually subdivided into immediate, recent, and remote memory. [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] Meningococcal Vaccines: Vaccines or candidate vaccines used to prevent infection with Neisseria meningitidis. [NIH] Menstrual Cycle: The period of the regularly recurring physiologic changes in the endometrium occurring during the reproductive period in human females and some primates and culminating in partial sloughing of the endometrium (menstruation). [NIH] Menstruation: The normal physiologic discharge through the vagina of blood and mucosal tissues from the nonpregnant uterus. [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] Mercury: A silver metallic element that exists as a liquid at room temperature. It has the atomic symbol Hg (from hydrargyrum, liquid silver), atomic number 80, and atomic weight 200.59. Mercury is used in many industrial applications and its salts have been employed therapeutically as purgatives, antisyphilitics, disinfectants, and astringents. It can be absorbed through the skin and mucous membranes which leads to mercury poisoning. Because of its toxicity, the clinical use of mercury and mercurials is diminishing. [NIH]

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Merozoite Surface Protein 1: A surface protein found on Plasmodium species which induces a T-cell response. The antigen is polymorphic, sharing amino acid sequence homology among Plasmodium falciparum, Plasmodium chabaudi, Plasmodium vivax, and Plasmodium yoelii. [NIH] Mesenchymal: Refers to cells that develop into connective tissue, blood vessels, and lymphatic tissue. [NIH] Metabolic disorder: A condition in which normal metabolic processes are disrupted, usually because of a missing enzyme. [NIH] Metabolite: Any substance produced by metabolism or by a metabolic process. [EU] Metabotropic: A glutamate receptor which triggers an increase in production of 2 intracellular messengers: diacylglycerol and inositol 1, 4, 5-triphosphate. [NIH] 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] Metastatic: Having to do with metastasis, which is the spread of cancer from one part of the body to another. [NIH] Metastatic cancer: Cancer that has spread from the place in which it started to other parts of the body. [NIH] Methionine: A sulfur containing essential amino acid that is important in many body functions. It is a chelating agent for heavy metals. [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 animals, lower algae, lower fungi, bacteria. [NIH] Microbiology: The study of microorganisms such as fungi, bacteria, algae, archaea, and viruses. [NIH] Microfilaments: The smallest of the cytoskeletal filaments. They are composed chiefly of actin. [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] Microtubules: Slender, cylindrical filaments found in the cytoskeleton of plant and animal cells. They are composed of the protein tubulin. [NIH] Migration: The systematic movement of genes between populations of the same species, geographic race, or variety. [NIH] Milk Hypersensitivity: Allergic reaction to milk (usually cow's milk) or milk products. In infants the hypersensitivity is manifested by colic, vomiting, diarrhea, rhinitis, wheezing, etc. Milk hypersensitivity should be differentiated from lactose intolerance, an intolerance to milk as a result of congenital deficiency of lactase. [NIH]

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Mineral Oil: A mixture of liquid hydrocarbons obtained from petroleum. It is used as laxative, lubricant, ointment base, and emollient. [NIH] Minority Groups: A subgroup having special characteristics within a larger group, often bound together by special ties which distinguish it from the larger group. [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] Mobilization: The process of making a fixed part or stored substance mobile, as by separating a part from surrounding structures to make it accessible for an operative procedure or by causing release into the circulation for body use of a substance stored in the body. [EU] 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 Probes: A group of atoms or molecules attached to other molecules or cellular structures and used in studying the properties of these molecules and structures. Radioactive DNA or RNA sequences are used in molecular genetics to detect the presence of a complementary sequence by molecular hybridization. [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] Monocyte: A type of white blood cell. [NIH] Mononuclear: A cell with one nucleus. [NIH] Mononucleosis: The presence of an abnormally large number of mononuclear leucocytes (monocytes) in the blood. The term is often used alone to refer to infectious mononucleosis. [EU]

Morbillivirus: A genus of the family Paramyxoviridae (subfamily Paramyxovirinae) where all the virions have hemagglutinin but not neuraminidase activity. All members produce both cytoplasmic and intranuclear inclusion bodies. MEASLES VIRUS is the type species. [NIH]

Morphine: The principal alkaloid in opium and the prototype opiate analgesic and narcotic. Morphine has widespread effects in the central nervous system and on smooth muscle. [NIH]

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Motility: The ability to move spontaneously. [EU] Motor Activity: The physical activity of an organism as a behavioral phenomenon. [NIH] Motor Endplate: The specialized postsynaptic region of a muscle cell. The motor endplate is immediately across the synaptic cleft from the presynaptic axon terminal. Among its anatomical specializations are junctional folds which harbor a high density of cholinergic receptors. [NIH] Motor nerve: An efferent nerve conveying an impulse that excites muscular contraction. [NIH]

Motor Neurons: Neurons which activate muscle cells. [NIH] Movement Disorders: Syndromes which feature dyskinesias as a cardinal manifestation of the disease process. Included in this category are degenerative, hereditary, post-infectious, medication-induced, post-inflammatory, and post-traumatic conditions. [NIH] Mucins: A secretion containing mucopolysaccharides and protein that is the chief constituent of mucus. [NIH] Mucosa: A mucous membrane, or tunica mucosa. [EU] Mucus: The viscous secretion of mucous membranes. It contains mucin, white blood cells, water, inorganic salts, and exfoliated cells. [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] 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 Contraction: A process leading to shortening and/or development of tension in muscle tissue. Muscle contraction occurs by a sliding filament mechanism whereby actin filaments slide inward among the myosin filaments. [NIH] Muscle relaxant: An agent that specifically aids in reducing muscle tension, as those acting at the polysynaptic neurons of motor nerves (e.g. meprobamate) or at the myoneural junction (curare and related compounds). [EU] Muscle Relaxation: That phase of a muscle twitch during which a muscle returns to a resting position. [NIH] Muscle tension: A force in a material tending to produce extension; the state of being stretched. [NIH] Myalgia: Pain in a muscle or muscles. [EU] 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]

Mycological: Relating to mycology, that is the science and study of fungi. [EU] Mycoplasma: A genus of gram-negative, facultatively anaerobic bacteria bounded by a plasma membrane only. Its organisms are parasites and pathogens, found on the mucous membranes of humans, animals, and birds. [NIH] Myelin: The fatty substance that covers and protects nerves. [NIH] Myelitis: Inflammation of the spinal cord. Relatively common etiologies include infections; autoimmune diseases; spinal cord; and ischemia (see also spinal cord vascular diseases). Clinical features generally include weakness, sensory loss, localized pain, incontinence, and

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other signs of autonomic dysfunction. [NIH] Myeloma: Cancer that arises in plasma cells, a type of white blood cell. [NIH] Myocarditis: Inflammation of the myocardium; inflammation of the muscular walls of the heart. [EU] Myocardium: The muscle tissue of the heart composed of striated, involuntary muscle known as cardiac muscle. [NIH] Myosin: Chief protein in muscle and the main constituent of the thick filaments of muscle fibers. In conjunction with actin, it is responsible for the contraction and relaxation of muscles. [NIH] Myositis: Inflammation of a voluntary muscle. [EU] Myositis Ossificans: A disease characterized by bony deposits or the ossification of muscle tissue. [NIH] Naive: Used to describe an individual who has never taken a certain drug or class of drugs (e. g., AZT-naive, antiretroviral-naive), or to refer to an undifferentiated immune system cell. [NIH] Narcotic: 1. Pertaining to or producing narcosis. 2. An agent that produces insensibility or stupor, applied especially to the opioids, i.e. to any natural or synthetic drug that has morphine-like actions. [EU] Nasal Mucosa: The mucous membrane lining the nasal cavity. [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] NCI: National Cancer Institute. NCI, part of the National Institutes of Health of the United 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] Neck Injuries: General or unspecified injuries to the neck. It includes injuries to the skin, muscles, and other soft tissues of the neck. [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] Needle Sharing: Usage of a single needle among two or more people for injecting drugs. Needle sharing is a high-risk behavior for contracting infectious disease. [NIH] Nelfinavir: A potent HIV protease inhibitor. It is used in combination with other antiviral drugs in the treatment of HIV in both adults and children. [NIH] Neonatal: Pertaining to the first four weeks after birth. [EU] Neonatal period: The first 4 weeks after birth. [NIH] Neonatorum: Patchy or generalized progressive hardening of the subcutaneous fat, often with fatal outcome, occurring in infants predisposed by reason of prematurity, marasmus, hypothermia, gastro-intestinal or respiratory infection, or gross malformations. [NIH] Neoplasm: A new growth of benign or malignant tissue. [NIH] Neoplastic: Pertaining to or like a neoplasm (= any new and abnormal growth); pertaining

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to neoplasia (= the formation of a neoplasm). [EU] Neostriatum: The phylogenetically newer part of the corpus striatum consisting of the caudate nucleus and putamen. It is often called simply the striatum. [NIH] 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] Nerve Endings: Specialized terminations of peripheral neurons. Nerve endings include neuroeffector junction(s) by which neurons activate target organs and sensory receptors which transduce information from the various sensory modalities and send it centrally in the nervous system. Presynaptic nerve endings are presynaptic terminals. [NIH] Nerve Growth Factor: Nerve growth factor is the first of a series of neurotrophic factors that were found to influence the growth and differentiation of sympathetic and sensory neurons. It is comprised of alpha, beta, and gamma subunits. The beta subunit is responsible for its growth stimulating activity. [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] Neuroanatomy: Study of the anatomy of the nervous system as a specialty or discipline. [NIH]

Neuroblastoma: Cancer that arises in immature nerve cells and affects mostly infants and children. [NIH] Neurodegenerative Diseases: Hereditary and sporadic conditions which are characterized by progressive nervous system dysfunction. These disorders are often associated with atrophy of the affected central or peripheral nervous system structures. [NIH] 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] Neuroglia: The non-neuronal cells of the nervous system. They are divided into macroglia (astrocytes, oligodendroglia, and schwann cells) and microglia. They not only provide physical support, but also respond to injury, regulate the ionic and chemical composition of the extracellular milieu, participate in the blood-brain and blood-retina barriers, form the myelin insulation of nervous pathways, guide neuronal migration during development, and exchange metabolites with neurons. Neuroglia have high-affinity transmitter uptake systems, voltage-dependent and transmitter-gated ion channels, and can release transmitters, but their role in signaling (as in many other functions) is unclear. [NIH] Neurologic: Having to do with nerves or the nervous system. [NIH] Neuromuscular: Pertaining to muscles and nerves. [EU] Neuromuscular Blocking Agents: Drugs that interrupt transmission of nerve impulses at the skeletal neuromuscular junction. They can be of two types, competitive, stabilizing blockers (neuromuscular nondepolarizing agents) or noncompetitive, depolarizing agents (neuromuscular depolarizing agents). Both prevent acetylcholine from triggering the muscle contraction and they are used as anesthesia adjuvants, as relaxants during electroshock, in convulsive states, etc. [NIH] Neuromuscular Depolarizing Agents: Drugs that interrupt transmission at the skeletal neuromuscular junction by causing sustained depolarization of the motor end plate. These

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agents are primarily used as adjuvants in surgical anesthesia to cause skeletal muscle relaxation. [NIH] Neuromuscular Junction: The synapse between a neuron and a muscle. [NIH] Neuromuscular Nondepolarizing Agents: Drugs that interrupt transmission at the skeletal neuromuscular junction without causing depolarization of the motor end plate. They prevent acetylcholine from triggering muscle contraction and are used as muscle relaxants during electroshock treatments, in convulsive states, and as anesthesia adjuvants. [NIH] Neuronal: Pertaining to a neuron or neurons (= conducting cells of the nervous system). [EU] Neuronal Plasticity: The capacity of the nervous system to change its reactivity as the result of successive activations. [NIH] 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] Neuropeptides: Peptides released by neurons as intercellular messengers. Many neuropeptides are also hormones released by non-neuronal cells. [NIH] Neurophysiology: The scientific discipline concerned with the physiology of the nervous system. [NIH] Neurosurgery: A surgical specialty concerned with the treatment of diseases and disorders of the brain, spinal cord, and peripheral and sympathetic nervous system. [NIH] Neurotoxic: Poisonous or destructive to nerve tissue. [EU] Neurotoxicity: The tendency of some treatments to cause damage to the nervous system. [NIH]

Neurotoxin: A substance that is poisonous to nerve tissue. [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] Neutralization: An act or process of neutralizing. [EU] 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] Neutrophils: Granular leukocytes having a nucleus with three to five lobes connected by slender threads of chromatin, and cytoplasm containing fine inconspicuous granules and stainable by neutral dyes. [NIH] Nevirapine: A potent, non-nucleoside reverse transcriptase inhibitor used in combination with nucleoside analogues for treatment of HIV infection and AIDS. [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] Non-nucleoside: A member of a class of compounds, including delavirdine, loviride and nevirapine, that acts to directly combine with and block the action of HIV's reverse transcriptase. [NIH]

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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] 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] Nucleus: A body of specialized protoplasm found in nearly all cells and containing the chromosomes. [NIH] Observational study: An epidemiologic study that does not involve any intervention, experimental or otherwise. Such a study may be one in which nature is allowed to take its course, with changes in one characteristic being studied in relation to changes in other characteristics. Analytical epidemiologic methods, such as case-control and cohort study designs, are properly called observational epidemiology because the investigator is observing without intervention other than to record, classify, count, and statistically analyze results. [NIH] Occult: Obscure; concealed from observation, difficult to understand. [EU] Occult Blood: Chemical, spectroscopic, or microscopic detection of extremely small amounts of blood. [NIH] Occupational Health: The promotion and maintenance of physical and mental health in the work environment. [NIH] Ocular: 1. Of, pertaining to, or affecting the eye. 2. Eyepiece. [EU] Oculi: Globe or ball of the eye. [NIH] Odds Ratio: The ratio of two odds. The exposure-odds ratio for case control data is the ratio of the odds in favor of exposure among cases to the odds in favor of exposure among noncases. The disease-odds ratio for a cohort or cross section is the ratio of the odds in favor of disease among the exposed to the odds in favor of disease among the unexposed. The prevalence-odds ratio refers to an odds ratio derived cross-sectionally from studies of prevalent cases. [NIH] Office Visits: Visits made by patients to health service providers' offices for diagnosis, treatment, and follow-up. [NIH] Oligosaccharides: Carbohydrates consisting of between two and ten monosaccharides connected by either an alpha- or beta-glycosidic link. They are found throughout nature in

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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] Omega-3 fatty acid: A type of fat obtained in the diet and involved in immunity. [NIH] Onchocerciasis: Infection with nematodes of the genus Onchocerca. Characteristics include the presence of firm subcutaneous nodules filled with adult worms, pruritus, and ocular lesions. [NIH] Opacity: Degree of density (area most dense taken for reading). [NIH] Opioid Peptides: The endogenous peptides with opiate-like activity. The three major classes currently recognized are the enkephalins, the dynorphins, and the endorphins. Each of these families derives from different precursors, proenkephalin, prodynorphin, and proopiomelanocortin, respectively. There are also at least three classes of opioid receptors, but the peptide families do not map to the receptors in a simple way. [NIH] Opisthotonos: A form of spasm in which the head and the heels are bent backward and the body bowed forward. [EU] Opium: The air-dried exudate from the unripe seed capsule of the opium poppy, Papaver somniferum, or its variant, P. album. It contains a number of alkaloids, but only a few morphine, codeine, and papaverine - have clinical significance. Opium has been used as an analgesic, antitussive, antidiarrheal, and antispasmodic. [NIH] Opsin: A protein formed, together with retinene, by the chemical breakdown of metarhodopsin. [NIH] Optic Nerve: The 2nd cranial nerve. The optic nerve conveys visual information from the retina to the brain. The nerve carries the axons of the retinal ganglion cells which sort at the optic chiasm and continue via the optic tracts to the brain. The largest projection is to the lateral geniculate nuclei; other important targets include the superior colliculi and the suprachiasmatic nuclei. Though known as the second cranial nerve, it is considered part of the central nervous system. [NIH] Oral Health: The optimal state of the mouth and normal functioning of the organs of the mouth without evidence of disease. [NIH] Orbicularis: A thin layer of fibers that originates at the posterior lacrimal crest and passes outward and forward, dividing into two slips which surround the canaliculi. [NIH] Orbit: One of the two cavities in the skull which contains an eyeball. Each eye is located in a bony socket or orbit. [NIH] Orbital: Pertaining to the orbit (= the bony cavity that contains the eyeball). [EU] Orchiectomy: The surgical removal of one or both testicles. [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] Orgasm: The crisis of sexual excitement in either humans or animals. [NIH] Ornithine: An amino acid produced in the urea cycle by the splitting off of urea from arginine. [NIH] Orofacial: Of or relating to the mouth and face. [EU] Osmolarity: The concentration of osmotically active particles expressed in terms of osmoles of solute per litre of solution. [EU] Osmotic: Pertaining to or of the nature of osmosis (= the passage of pure solvent from a

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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] Ossification: The formation of bone or of a bony substance; the conversion of fibrous tissue or of cartilage into bone or a bony substance. [EU] Osteomyelitis: Inflammation of bone caused by a pyogenic organism. It may remain localized or may spread through the bone to involve the marrow, cortex, cancellous tissue, and periosteum. [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] Ovary: Either of the paired glands in the female that produce the female germ cells and secrete some of the female sex hormones. [NIH] Ovum: A female germ cell extruded from the ovary at ovulation. [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]

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 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] Paediatric: Of or relating to the care and medical treatment of children; belonging to or concerned with paediatrics. [EU] Palliative: 1. Affording relief, but not cure. 2. An alleviating medicine. [EU] Palsy: Disease of the peripheral nervous system occurring usually after many years of increased lead absorption. [NIH] 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] 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

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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] Par excellence: The petrous portion of the temporal bone, containing the inner ear and wedged in at the base of the skull between the sphenoid and occipital bones. [NIH] Paraganglia, Chromaffin: Small bodies containing chromaffin cells occurring outside of the adrenal medulla, most commonly near the sympathetic ganglia and in organs such as the kidney, liver, heart and gonads. [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] Parenteral: Not through the alimentary canal but rather by injection through some other route, as subcutaneous, intramuscular, intraorbital, intracapsular, intraspinal, intrasternal, intravenous, etc. [EU] Parietal: 1. Of or pertaining to the walls of a cavity. 2. Pertaining to or located near the parietal bone, as the parietal lobe. [EU] Parietal Cells: Cells in the stomach wall that make hydrochloric acid. [NIH] Parietal Lobe: Upper central part of the cerebral hemisphere. [NIH] Paroxysmal: Recurring in paroxysms (= spasms or seizures). [EU] 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] 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] Pathophysiology: Altered functions in an individual or an organ due to disease. [NIH] Patient Care Team: Care of patients by a multidisciplinary team usually organized under the leadership of a physician; each member of the team has specific responsibilities and the whole team contributes to the care of the patient. [NIH] Patient Education: The teaching or training of patients concerning their own health needs. [NIH]

Pelvic: Pertaining to the pelvis. [EU] Pemphigus: Group of chronic blistering diseases characterized histologically by acantholysis and blister formation within the epidermis. [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]

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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] Peptic: Pertaining to pepsin or to digestion; related to the action of gastric juices. [EU] Peptic Ulcer: Ulcer that occurs in those portions of the alimentary tract which come into contact with gastric juice containing pepsin and acid. It occurs when the amount of acid and pepsin is sufficient to overcome the gastric mucosal barrier. [NIH] Peptide: Any compound consisting of two or more amino acids, the building blocks of proteins. Peptides are combined to make proteins. [NIH] Peptide T: N-(N-(N(2)-(N-(N-(N-(N-D-Alanyl L-seryl)-L-threonyl)-L-threonyl) L-threonyl)L-asparaginyl)-L-tyrosyl) L-threonine. Octapeptide sharing sequence homology with HIV envelope protein gp120. It is potentially useful as antiviral agent in AIDS therapy. The core pentapeptide sequence, TTNYT, consisting of amino acids 4-8 in peptide T, is the HIV envelope sequence required for attachment to the CD4 receptor. [NIH] Perfusion: Bathing an organ or tissue with a fluid. In regional perfusion, a specific area of the body (usually an arm or a leg) receives high doses of anticancer drugs through a blood vessel. Such a procedure is performed to treat cancer that has not spread. [NIH] Pericardium: The fibroserous sac surrounding the heart and the roots of the great vessels. [NIH]

Perinatal: Pertaining to or occurring in the period shortly before and after birth; variously defined as beginning with completion of the twentieth to twenty-eighth week of gestation and ending 7 to 28 days after birth. [EU] Perineal: Pertaining to the perineum. [EU] Peripheral blood: Blood circulating throughout the body. [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] Pertussis: An acute, highly contagious infection of the respiratory tract, most frequently affecting young children, usually caused by Bordetella pertussis; a similar illness has been associated with infection by B. parapertussis and B. bronchiseptica. It is characterized by a catarrhal stage, beginning after an incubation period of about two weeks, with slight fever, sneezing, running at the nose, and a dry cough. In a week or two the paroxysmal stage begins, with the characteristic paroxysmal cough, consisting of a deep inspiration, followed by a series of quick, short coughs, continuing until the air is expelled from the lungs; the close of the paroxysm is marked by a long-drawn, shrill, whooping inspiration, due to spasmodic closure of the glottis. This stage lasts three to four weeks, after which the convalescent stage begins, in which paroxysms grow less frequent and less violent, and finally cease. Called also whooping cough. [EU] Pertussis Toxins: Any of various biologically active proteins or toxins elaborated by Bordetella pertussis that cause the symptoms of whooping cough. Some activate pancreatic islets, others inhibit the adenylate cyclase cascade and some cause lymphocytosis. [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

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combustible fuels, petrochemicals, and lubricants. [NIH] Pharmaceutical Preparations: Drugs intended for human or veterinary use, presented in their finished dosage form. Included here are materials used in the preparation and/or formulation of the finished dosage form. [NIH] Pharmacokinetic: The mathematical analysis of the time courses of absorption, distribution, and elimination of drugs. [NIH] Pharmacologic: Pertaining to pharmacology or to the properties and reactions of drugs. [EU] Pharynx: The hollow tube about 5 inches long that starts behind the nose and ends at the top of the trachea (windpipe) and esophagus (the tube that goes to the stomach). [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 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] Phospholipases: A class of enzymes that catalyze the hydrolysis of phosphoglycerides or glycerophosphatidates. EC 3.1.-. [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] 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] Physical Examination: Systematic and thorough inspection of the patient for physical signs of disease or abnormality. [NIH] Physical Fitness: A state of well-being in which performance is optimal, often as a result of physical conditioning which may be prescribed for disease therapy. [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] Phytotoxin: A substance which is toxic for plants. [NIH] Pigment: A substance that gives color to tissue. Pigments are responsible for the color of skin, eyes, and hair. [NIH] Pilot study: The initial study examining a new method or treatment. [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] Plague: An acute infectious disease caused by Yersinia pestis that affects humans, wild rodents, and their ectoparasites. This condition persists due to its firm entrenchment in sylvatic rodent-flea ecosystems throughout the world. Bubonic plague is the most common

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form. [NIH] Plant Diseases: Diseases of plants. [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] Plaque: A clear zone in a bacterial culture grown on an agar plate caused by localized destruction of bacterial cells by a bacteriophage. The concentration of infective virus in a fluid can be estimated by applying the fluid to a culture and counting the number of. [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 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] Plasma Volume: Volume of plasma in the circulation. It is usually measured by indicator dilution techniques. [NIH] Plasmids: Any extrachromosomal hereditary determinant. Plasmids are self-replicating circular molecules of DNA that are found in a variety of bacterial, archaeal, fungal, algal, and plant species. [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] Plasticity: In an individual or a population, the capacity for adaptation: a) through gene changes (genetic plasticity) or b) through internal physiological modifications in response to changes of environment (physiological plasticity). [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] Pneumococcal Vaccines: Vaccines or candidate vaccines used to prevent infections with Streptococcus pneumoniae. [NIH] Poisoning: A condition or physical state produced by the ingestion, injection or inhalation of, or exposure to a deleterious agent. [NIH] Pollen: The male fertilizing element of flowering plants analogous to sperm in animals. It is

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released from the anthers as yellow dust, to be carried by insect or other vectors, including wind, to the ovary (stigma) of other flowers to produce the embryo enclosed by the seed. The pollens of many plants are allergenic. [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]

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] Polypeptide: A peptide which on hydrolysis yields more than two amino acids; called tripeptides, tetrapeptides, etc. according to the number of amino acids contained. [EU] Polysaccharide: A type of carbohydrate. It contains sugar molecules that are linked together chemically. [NIH] Polyvalent: Having more than one valence. [EU] Pons: The part of the central nervous system lying between the medulla oblongata and the mesencephalon, ventral to the cerebellum, and consisting of a pars dorsalis and a pars ventralis. [NIH] Population Characteristics: Qualities and characterization of various types of populations within a social or geographic group, with emphasis on demography, health status, and socioeconomic factors. [NIH] Port: An implanted device through which blood may be withdrawn and drugs may be infused without repeated needle sticks. Also called a port-a-cath. [NIH] Port-a-cath: An implanted device through which blood may be withdrawn and drugs may be infused without repeated needle sticks. Also called a port. [NIH] Positive pressure ventilation: Provision of oxygen under pressure by a mechanical respirator. [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-synaptic: Nerve potential generated by an inhibitory hyperpolarizing stimulation. [NIH] Post-traumatic: Occurring as a result of or after injury. [EU] Potassium: An element that is in the alkali group of metals. It has an atomic symbol K, atomic number 19, and atomic weight 39.10. It is the chief cation in the intracellular fluid of muscle and other cells. Potassium ion is a strong electrolyte and it plays a significant role in the regulation of fluid volume and maintenance of the water-electrolyte balance. [NIH] Potentiate: A degree of synergism which causes the exposure of the organism to a harmful substance to worsen a disease already contracted. [NIH] Potentiating: 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]

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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] Preclinical: Before a disease becomes clinically recognizable. [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] Presynaptic: Situated proximal to a synapse, or occurring before the synapse is crossed. [EU] Presynaptic Terminals: The distal terminations of axons which are specialized for the release of neurotransmitters. Also included are varicosities along the course of axons which have similar specializations and also release transmitters. Presynaptic terminals in both the central and peripheral nervous systems are included. [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] Preventive Medicine: A medical specialty primarily concerned with prevention of disease and the promotion and preservation of health in the individual. [NIH] Primary Prevention: Prevention of disease or mental disorders in susceptible individuals or populations through promotion of health, including mental health, and specific protection, as in immunization, as distinguished from the prevention of complications or after-effects of existing disease. [NIH] Primary tumor: The original tumor. [NIH] Primary vaccination: First or principal vaccination ( = introduction of a vaccine into the body for the purpose of inducing immunity). [EU] 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] Procaine: A local anesthetic of the ester type that has a slow onset and a short duration of action. It is mainly used for infiltration anesthesia, peripheral nerve block, and spinal block. (From Martindale, The Extra Pharmacopoeia, 30th ed, p1016). [NIH] Proctocolitis: Inflammation of the rectum and colon. [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] Prognostic factor: A situation or condition, or a characteristic of a patient, that can be used to estimate the chance of recovery from a disease, or the chance of the disease recurring (coming back). [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]

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Projection: A defense mechanism, operating unconsciously, whereby that which is emotionally unacceptable in the self is rejected and attributed (projected) to others. [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] Pro-Opiomelanocortin: A precursor protein, MW 30,000, synthesized mainly in the anterior pituitary gland but also found in the hypothalamus, brain, and several peripheral tissues. It incorporates the amino acid sequences of ACTH and beta-lipotropin. These two hormones, in turn, contain the biologically active peptides MSH, corticotropin-like intermediate lobe peptide, alpha-lipotropin, endorphins, and methionine enkephalin. [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] Prospective Studies: Observation of a population for a sufficient number of persons over a sufficient number of years to generate incidence or mortality rates subsequent to the selection of the study group. [NIH] Prospective study: An epidemiologic study in which a group of individuals (a cohort), all free of a particular disease and varying in their exposure to a possible risk factor, is followed over a specific amount of time to determine the incidence rates of the disease in the exposed and unexposed groups. [NIH] Prostaglandin: Any of a group of components derived from unsaturated 20-carbon fatty acids, primarily arachidonic acid, via the cyclooxygenase pathway that are extremely potent mediators of a diverse group of physiologic processes. The abbreviation for prostaglandin is PG; specific compounds are designated by adding one of the letters A through I to indicate the type of substituents found on the hydrocarbon skeleton and a subscript (1, 2 or 3) to indicate the number of double bonds in the hydrocarbon skeleton e.g., PGE2. The predominant naturally occurring prostaglandins all have two double bonds and are synthesized from arachidonic acid (5,8,11,14-eicosatetraenoic acid) by the pathway shown in the illustration. The 1 series and 3 series are produced by the same pathway with fatty acids having one fewer double bond (8,11,14-eicosatrienoic acid or one more double bond (5,8,11,14,17-eicosapentaenoic acid) than arachidonic acid. The subscript a or ß indicates the configuration at C-9 (a denotes a substituent below the plane of the ring, ß, above the plane). The naturally occurring PGF's have the a configuration, e.g., PGF2a. All of the prostaglandins act by binding to specific cell-surface receptors causing an increase in the level of the intracellular second messenger cyclic AMP (and in some cases cyclic GMP also). The effect produced by the cyclic AMP increase depends on the specific cell type. In some cases there is also a positive feedback effect. Increased cyclic AMP increases prostaglandin synthesis leading to further increases in cyclic AMP. [EU] Prostaglandins A: (13E,15S)-15-Hydroxy-9-oxoprosta-10,13-dien-1-oic acid (PGA(1)); (5Z,13E,15S)-15-hydroxy-9-oxoprosta-5,10,13-trien-1-oic acid (PGA(2)); (5Z,13E,15S,17Z)-15hydroxy-9-oxoprosta-5,10,13,17-tetraen-1-oic acid (PGA(3)). A group of naturally occurring secondary prostaglandins derived from PGE. PGA(1) and PGA(2) as well as their 19hydroxy derivatives are found in many organs and tissues. [NIH] 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

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lower part of the pubic symphysis, above the deep layer of the triangular ligament, and rests upon the rectum. [NIH] Prostate gland: A gland in the male reproductive system just below the bladder. It surrounds part of the urethra, the canal that empties the bladder, and produces a fluid that forms part of semen. [NIH] Prostatitis: Inflammation of the prostate. [EU] Prosthesis: An artificial replacement of a part of the body. [NIH] Protease: Proteinase (= any enzyme that catalyses the splitting of interior peptide bonds in a protein). [EU] Protease Inhibitors: Compounds which inhibit or antagonize biosynthesis or actions of proteases (endopeptidases). [NIH] Protein Binding: The process in which substances, either endogenous or exogenous, bind to proteins, peptides, enzymes, protein precursors, or allied compounds. Specific proteinbinding measures are often used as assays in diagnostic assessments. [NIH] 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 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] Protein-Tyrosine Kinase: An enzyme that catalyzes the phosphorylation of tyrosine residues in proteins with ATP or other nucleotides as phosphate donors. EC 2.7.1.112. [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] 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] Proto-Oncogene Proteins c-mos: Cellular proteins encoded by the c-mos genes. They

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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] Proximal: Nearest; closer to any point of reference; opposed to distal. [EU] Pruritic: Pertaining to or characterized by pruritus. [EU] Pruritus: An intense itching sensation that produces the urge to rub or scratch the skin to obtain relief. [NIH] Pseudomonas: A genus of gram-negative, aerobic, rod-shaped bacteria widely distributed in nature. Some species are pathogenic for humans, animals, and plants. [NIH] Pseudomonas aeruginosa: A species of gram-negative, aerobic, rod-shaped bacteria commonly isolated from clinical specimens (wound, burn, and urinary tract infections). It is also found widely distributed in soil and water. P. aeruginosa is a major agent of nosocomial infection. [NIH] Psychiatry: The medical science that deals with the origin, diagnosis, prevention, and treatment of mental disorders. [NIH] Psychic: Pertaining to the psyche or to the mind; mental. [EU] Psychogenic: Produced or caused by psychic or mental factors rather than organic factors. [EU]

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 Artery: The short wide vessel arising from the conus arteriosus of the right ventricle and conveying unaerated blood to the lungs. [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] Pustular: Pertaining to or of the nature of a pustule; consisting of pustules (= a visible

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collection of pus within or beneath the epidermis). [EU] Putamen: The largest and most lateral of the basal ganglia lying between the lateral medullary lamina of the globus pallidus and the external capsule. It is part of the neostriatum and forms part of the lentiform nucleus along with the globus pallidus. [NIH] Putrefaction: The process of decomposition of animal and vegetable matter by living organisms. [NIH] Pyogenic: Producing pus; pyopoietic (= liquid inflammation product made up of cells and a thin fluid called liquor puris). [EU] Pyramidal Cells: Projection neurons in the cerebral cortex and the hippocampus. Pyramidal cells have a pyramid-shaped soma with the apex and an apical dendrite pointed toward the pial surface and other dendrites and an axon emerging from the base. The axons may have local collaterals but also project outside their cortical region. [NIH] Pyridoxal: 3-Hydroxy-5-(hydroxymethyl)-2-methyl-4- pyridinecarboxaldehyde. [NIH] Pyrogenic: Inducing fever. [EU] Quaternary: 1. Fourth in order. 2. Containing four elements or groups. [EU] Quiescent: Marked by a state of inactivity or repose. [EU] Rabies: A highly fatal viral infection of the nervous system which affects all warm-blooded animal species. It is one of the most important of the zoonoses because of the inevitably fatal outcome for the infected human. [NIH] Race: A population within a species which exhibits general similarities within itself, but is both discontinuous and distinct from other populations of that species, though not sufficiently so as to achieve the status of a taxon. [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] Radiation therapy: The use of high-energy radiation from x-rays, gamma rays, neutrons, and other sources to kill cancer cells and shrink tumors. Radiation may come from a machine outside the body (external-beam radiation therapy), or it may come from radioactive material placed in the body in the area near cancer cells (internal radiation therapy, implant radiation, or brachytherapy). Systemic radiation therapy uses a radioactive substance, such as a radiolabeled monoclonal antibody, that circulates throughout the body. Also called radiotherapy. [NIH] Radioactive: Giving off radiation. [NIH] Radiography: Examination of any part of the body for diagnostic purposes by means of roentgen rays, recording the image on a sensitized surface (such as photographic film). [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] Radiolabeled: Any compound that has been joined with a radioactive substance. [NIH] Radiopharmaceutical: Any medicinal product which, when ready for use, contains one or more radionuclides (radioactive isotopes) included for a medicinal purpose. [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] Reabsorption: 1. The act or process of absorbing again, as the selective absorption by the kidneys of substances (glucose, proteins, sodium, etc.) already secreted into the renal tubules, and their return to the circulating blood. 2. Resorption. [EU]

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Reactivation: The restoration of activity to something that has been inactivated. [EU] 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] Receptors, Serotonin: Cell-surface proteins that bind serotonin and trigger intracellular changes which influence the behavior of cells. Several types of serotonin receptors have been recognized which differ in their pharmacology, molecular biology, and mode of action. [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] Refer: To send or direct for treatment, aid, information, de decision. [NIH] Reflex: An involuntary movement or exercise of function in a part, excited in response to a stimulus applied to the periphery and transmitted to the brain or spinal cord. [NIH] Refraction: A test to determine the best eyeglasses or contact lenses to correct a refractive error (myopia, hyperopia, or astigmatism). [NIH] 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] Relapse: The return of signs and symptoms of cancer after a period of improvement. [NIH] Relaxant: 1. Lessening or reducing tension. 2. An agent that lessens tension. [EU] Renal failure: Progressive renal insufficiency and uremia, due to irreversible and progressive renal glomerular tubular or interstitial disease. [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] Renin-Angiotensin System: A system consisting of renin, angiotensin-converting enzyme, and angiotensin II. Renin, an enzyme produced in the kidney, acts on angiotensinogen, an alpha-2 globulin produced by the liver, forming angiotensin I. The converting enzyme contained in the lung acts on angiotensin I in the plasma converting it to angiotensin II, the most powerful directly pressor substance known. It causes contraction of the arteriolar smooth muscle and has other indirect actions mediated through the adrenal cortex. [NIH] Reperfusion: Restoration of blood supply to tissue which is ischemic due to decrease in

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normal blood supply. The decrease may result from any source including atherosclerotic obstruction, narrowing of the artery, or surgical clamping. It is primarily a procedure for treating infarction or other ischemia, by enabling viable ischemic tissue to recover, thus limiting further necrosis. However, it is thought that reperfusion can itself further damage the ischemic tissue, causing reperfusion injury. [NIH] Reperfusion Injury: Functional, metabolic, or structural changes, including necrosis, in ischemic tissues thought to result from reperfusion to ischemic areas of the tissue. The most common instance is myocardial reperfusion injury. [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] Research Support: Financial support of research activities. [NIH] Residual disease: Cancer cells that remain after attempts have been made to remove the cancer. [NIH] 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 (= cell respiration). [NIH] Respirator: A mechanical device that helps a patient breathe; a mechanical ventilator. [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] Respiratory failure: Inability of the lungs to conduct gas exchange. [NIH] Respiratory Physiology: Functions and activities of the respiratory tract as a whole or of any of its parts. [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] Retinal Ganglion Cells: Cells of the innermost nuclear layer of the retina, the ganglion cell layer, which project axons through the optic nerve to the brain. They are quite variable in size and in the shapes of their dendritic arbors, which are generally confined to the inner plexiform layer. [NIH] Retinoid: Vitamin A or a vitamin A-like compound. [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]

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Retinyl palmitate: A drug being studied in cancer prevention; it belongs to the family of drugs called retinoids. [NIH] Retrograde: 1. Moving backward or against the usual direction of flow. 2. Degenerating, deteriorating, or catabolic. [EU] Retrospective: Looking back at events that have already taken place. [NIH] Retrospective study: A study that looks backward in time, usually using medical records and interviews with patients who already have or had a disease. [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] 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 attaches to them and there receives molecules of transfer RNA bearing amino acids. [NIH] Ricin: A protein phytotoxin from the seeds of Ricinus communis, the castor oil plant. It agglutinates cells, is proteolytic, and causes lethal inflammation and hemorrhage if taken internally. [NIH] Risk factor: A habit, trait, condition, or genetic alteration that increases a person's chance of developing a disease. [NIH] Ritonavir: An HIV protease inhibitor that works by interfering with the reproductive cycle of HIV. [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] 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] 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] Sarcoplasmic Reticulum: A network of tubules and sacs in the cytoplasm of skeletal muscles that assist with muscle contraction and relaxation by releasing and storing calcium ions. [NIH] Saturate: Means fatty acids without double bond. [NIH]

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Scans: Pictures of structures inside the body. Scans often used in diagnosing, staging, and monitoring disease include liver scans, bone scans, and computed tomography (CT) or computerized axial tomography (CAT) scans and magnetic resonance imaging (MRI) scans. In liver scanning and bone scanning, radioactive substances that are injected into the bloodstream collect in these organs. A scanner that detects the radiation is used to create pictures. In CT scanning, an x-ray machine linked to a computer is used to produce detailed pictures of organs inside the body. MRI scans use a large magnet connected to a computer to create pictures of areas inside the body. [NIH] Schizoid: Having qualities resembling those found in greater degree in schizophrenics; a person of schizoid personality. [NIH] Schizophrenia: A mental disorder characterized by a special type of disintegration of the personality. [NIH] Schizotypal Personality Disorder: A personality disorder in which there are oddities of thought (magical thinking, paranoid ideation, suspiciousness), perception (illusions, depersonalization), speech (digressive, vague, overelaborate), and behavior (inappropriate affect in social interactions, frequently social isolation) that are not severe enough to characterize schizophrenia. [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] Scrotum: In males, the external sac that contains the testicles. [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] Secretory Vesicles: Vesicles derived from the golgi apparatus containing material to be released at the cell surface. [NIH] Sedative: 1. Allaying activity and excitement. 2. An agent that allays excitement. [EU] Sedentary: 1. Sitting habitually; of inactive habits. 2. Pertaining to a sitting posture. [EU] Sediment: A precipitate, especially one that is formed spontaneously. [EU] Segmental: Describing or pertaining to a structure which is repeated in similar form in successive segments of an organism, or which is undergoing segmentation. [NIH] Segmentation: The process by which muscles in the intestines move food and wastes through the body. [NIH] Seizures: Clinical or subclinical disturbances of cortical function due to a sudden, abnormal,

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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] 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] Seminal vesicles: Glands that help produce semen. [NIH] Seminiferous tubule: Tube used to transport sperm made in the testes. [NIH] Senescence: The bodily and mental state associated with advancing age. [NIH] 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] Sensory loss: A disease of the nerves whereby the myelin or insulating sheath of myelin on the nerves does not stay intact and the messages from the brain to the muscles through the nerves are not carried properly. [NIH] Sepsis: The presence of bacteria in the bloodstream. [NIH] 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] Septicemia: Systemic disease associated with the presence and persistence of pathogenic microorganisms or their toxins in the blood. Called also blood poisoning. [EU] Sequence Homology: The degree of similarity between sequences. Studies of amino acid and nucleotide sequences provide useful information about the genetic relatedness of certain species. [NIH] Sequencing: The determination of the order of nucleotides in a DNA or RNA chain. [NIH] Sequester: A portion of dead bone which has become detached from the healthy bone tissue, as occurs in necrosis. [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] Seroconversion: The change of a serologic test from negative to positive, indicating the development of antibodies in response to infection or immunization. [EU] Serologic: Analysis of a person's serum, especially specific immune or lytic serums. [NIH] Serotonin: A biochemical messenger and regulator, synthesized from the essential amino acid L-tryptophan. In humans it is found primarily in the central nervous system, gastrointestinal tract, and blood platelets. Serotonin mediates several important physiological functions including neurotransmission, gastrointestinal motility, hemostasis, and cardiovascular integrity. Multiple receptor families (receptors, serotonin) explain the broad physiological actions and distribution of this biochemical mediator. [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]

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Serum: The clear liquid part of the blood that remains after blood cells and clotting proteins have been removed. [NIH] Sex Characteristics: Those characteristics that distinguish one sex from the other. The primary sex characteristics are the ovaries and testes and their related hormones. Secondary sex characteristics are those which are masculine or feminine but not directly related to reproduction. [NIH] Sexually Transmitted Diseases: Diseases due to or propagated by sexual contact. [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] Sigmoid: 1. Shaped like the letter S or the letter C. 2. The sigmoid colon. [EU] Sigmoidoscopy: Endoscopic examination, therapy or surgery of the sigmoid flexure. [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] Skeletal: Having to do with the skeleton (boney part of the body). [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] Skin Tests: Epicutaneous or intradermal application of a sensitizer for demonstration of either delayed or immediate hypersensitivity. Used in diagnosis of hypersensitivity or as a test for cellular immunity. [NIH] Skull: The skeleton of the head including the bones of the face and the bones enclosing the brain. [NIH] Sleep apnea: A serious, potentially life-threatening breathing disorder characterized by repeated cessation of breathing due to either collapse of the upper airway during sleep or absence of respiratory effort. [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]

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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] Social Support: Support systems that provide assistance and encouragement to individuals with physical or emotional disabilities in order that they may better cope. Informal social support is usually provided by friends, relatives, or peers, while formal assistance is provided by churches, groups, etc. [NIH] Socioeconomic Factors: Social and economic factors that characterize the individual or group within the social structure. [NIH] Sodium: An element that is a member of the alkali group of metals. It has the atomic symbol Na, atomic number 11, and atomic weight 23. With a valence of 1, it has a strong affinity for oxygen and other nonmetallic elements. Sodium provides the chief cation of the extracellular body fluids. Its salts are the most widely used in medicine. (From Dorland, 27th ed) Physiologically the sodium ion plays a major role in blood pressure regulation, maintenance of fluid volume, and electrolyte balance. [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] Solitary Nucleus: Gray matter located in the dorsomedial part of the medulla oblongata associated with the solitary tract. The solitary nucleus receives inputs from most organ systems including the terminations of the facial, glossopharyngeal, and vagus nerves. It is a major coordinator of autonomic nervous system regulation of cardiovascular, respiratory, gustatory, gastrointestinal, and chemoreceptive aspects of homeostasis. The solitary nucleus is also notable for the large number of neurotransmitters which are found therein. [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] Soma: The body as distinct from the mind; all the body tissue except the germ cells; all the axial body. [NIH] 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 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] Spasm: An involuntary contraction of a muscle or group of muscles. Spasms may involve skeletal muscle or smooth muscle. [NIH] Spasmodic: Of the nature of a spasm. [EU] 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

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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] Sperm Maturation: Posttesticular ripening of spermatozoa. [NIH] Sperm Motility: Ability of the spermatozoon to move by flagellate swimming. [NIH] Spermatogenesis: Process of formation and development of spermatozoa, including spermatocytogenesis and spermiogenesis. [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] Spermatozoon: The mature male germ cell. [NIH] Sphenoid: An unpaired cranial bone with a body containing the sphenoid sinus and forming the posterior part of the medial walls of the orbits. [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] Spinal Cord Vascular Diseases: Hypoxic-ischemic and hemorrhagic disorders of the spinal cord. Arteriosclerosis, emboli, and vascular malformations are potential causes of these conditions. [NIH] Spinal Nerves: The 31 paired peripheral nerves formed by the union of the dorsal and ventral spinal roots from each spinal cord segment. The spinal nerve plexuses and the spinal roots are also included. [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] Sporotrichosis: The commonest and least serious of the deep mycoses, characterized by nodular lesions of the cutaneous and subcutaneous tissues. It is caused by inhalation of contaminated dust or by infection of a wound. [NIH] Squamous: Scaly, or platelike. [EU] Squamous cell carcinoma: Cancer that begins in squamous cells, which are thin, flat cells resembling fish scales. Squamous cells are found in the tissue that forms the surface of the skin, the lining of the hollow organs of the body, and the passages of the respiratory and digestive tracts. Also called epidermoid carcinoma. [NIH]

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Squamous cell carcinoma: Cancer that begins in squamous cells, which are thin, flat cells resembling fish scales. Squamous cells are found in the tissue that forms the surface of the skin, the lining of the hollow organs of the body, and the passages of the respiratory and digestive tracts. Also called epidermoid carcinoma. [NIH] Squamous cells: Flat cells that look like fish scales under a microscope. These cells cover internal and external surfaces of the body. [NIH] Stabilizer: A device for maintaining constant X-ray tube voltage or current. [NIH] Staging: Performing exams and tests to learn the extent of the cancer within the body, especially whether the disease has spread from the original site to other parts of the body. [NIH]

Staphylococcus: A genus of gram-positive, facultatively anaerobic, coccoid bacteria. Its 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] Steel: A tough, malleable, iron-based alloy containing up to, but no more than, two percent carbon and often other metals. It is used in medicine and dentistry in implants and instrumentation. [NIH] Stem cell transplantation: A method of replacing immature blood-forming cells that were destroyed by cancer treatment. The stem cells are given to the person after treatment to help the bone marrow recover and continue producing healthy blood cells. [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] Stereotactic: Radiotherapy that treats brain tumors by using a special frame affixed directly to the patient's cranium. By aiming the X-ray source with respect to the rigid frame, technicians can position the beam extremely precisely during each treatment. [NIH] Stereotaxis: Use of a computer and scanning devices to create three-dimensional pictures. This method can be used to direct a biopsy, external radiation, or the insertion of radiation implants. [NIH] Sterile: Unable to produce children. [NIH] Sterility: 1. The inability to produce offspring, i.e., the inability to conceive (female s.) or to induce conception (male s.). 2. The state of being aseptic, or free from microorganisms. [EU] Sterilization: The destroying of all forms of life, especially microorganisms, by heat, chemical, or other means. [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

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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] Strabismus: Deviation of the eye which the patient cannot overcome. The visual axes assume a position relative to each other different from that required by the physiological conditions. The various forms of strabismus are spoken of as tropias, their direction being indicated by the appropriate prefix, as cyclo tropia, esotropia, exotropia, hypertropia, and hypotropia. Called also cast, heterotropia, manifest deviation, and squint. [EU] Streptococcal: Caused by infection due to any species of streptococcus. [NIH] Streptococcal Infections: Infections with bacteria of the genus 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] Striatum: A higher brain's domain thus called because of its stripes. [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] Stroke Volume: The amount of blood pumped out of the heart per beat not to be confused with cardiac output (volume/time). [NIH] Stromal: Large, veil-like cell in the bone marrow. [NIH] 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] Subiculum: A region of the hippocampus that projects to other areas of the brain. [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] Succinylcholine: A quaternary skeletal muscle relaxant usually used in the form of its bromide, chloride, or iodide. It is a depolarizing relaxant, acting in about 30 seconds and with a duration of effect averaging three to five minutes. Succinylcholine is used in surgical,

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anesthetic, and other procedures in which a brief period of muscle relaxation is called for. [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] Sufentanil: An opioid analgesic that is used as an adjunct in anesthesia, in balanced anesthesia, and as a primary anesthetic agent. [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] Supplementation: Adding nutrients to the diet. [NIH] Suppositories: A small cone-shaped medicament having cocoa butter or gelatin at its basis and usually intended for the treatment of local conditions in the rectum. [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] Supraspinal: Above the spinal column or any spine. [NIH] Surface Plasmon Resonance: A biosensing technique in which biomolecules capable of binding to specific analytes or ligands are first immobilized on one side of a metallic film. Light is then focused on the opposite side of the film to excite the surface plasmons, that is, the oscillations of free electrons propagating along the film's surface. The refractive index of light reflecting off this surface is measured. When the immobilized biomolecules are bound by their ligands, an alteration in surface plasmons on the opposite side of the film is created which is directly proportional to the change in bound, or adsorbed, mass. Binding is measured by changes in the refractive index. The technique is used to study biomolecular interactions, such as antigen-antibody binding. [NIH] 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]

Suspensions: Colloids with liquid continuous phase and solid dispersed phase; the term is used loosely also for solid-in-gas (aerosol) and other colloidal systems; water-insoluble drugs may be given as suspensions. [NIH] Sympathetic Nervous System: The thoracolumbar division of the autonomic nervous system. Sympathetic preganglionic fibers originate in neurons of the intermediolateral column of the spinal cord and project to the paravertebral and prevertebral ganglia, which in turn project to target organs. The sympathetic nervous system mediates the body's response to stressful situations, i.e., the fight or flight reactions. It often acts reciprocally to the parasympathetic system. [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

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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] Synapsis: The pairing between homologous chromosomes of maternal and paternal origin during the prophase of meiosis, leading to the formation of gametes. [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] Synaptic Transmission: The communication from a neuron to a target (neuron, muscle, or secretory cell) across a synapse. In chemical synaptic transmission, the presynaptic neuron releases a neurotransmitter that diffuses across the synaptic cleft and binds to specific synaptic receptors. These activated receptors modulate ion channels and/or secondmessenger systems to influence the postsynaptic cell. Electrical transmission is less common in the nervous system, and, as in other tissues, is mediated by gap junctions. [NIH] Synaptic Vesicles: Membrane-bound compartments which contain transmitter molecules. Synaptic vesicles are concentrated at presynaptic terminals. They actively sequester transmitter molecules from the cytoplasm. In at least some synapses, transmitter release occurs by fusion of these vesicles with the presynaptic membrane, followed by exocytosis of their contents. [NIH] Synaptophysin: A 38-kDa integral membrane glycoprotein of the presynaptic vesicles in neuron and neuroendocrine cells. It is expressed by a variety of normal and neoplastic neuroendocrine cells and is therefore used as an immunocytochemical marker for neuroendocrine differentiation in various tumors. In Alzheimer disease and other dementing disorders there is an important synapse loss due in part to a decrease of synaptophysin in the presynaptic vesicles. [NIH] Synaptosomes: Pinched-off nerve endings and their contents of vesicles and cytoplasm together with the attached subsynaptic area of the membrane of the post-synaptic cell. They are largely artificial structures produced by fractionation after selective centrifugation of nervous tissue homogenates. [NIH] Synergistic: Acting together; enhancing the effect of another force or agent. [EU] Syphilis: A contagious venereal disease caused by the spirochete Treponema pallidum. [NIH]

Systemic: Affecting the entire body. [NIH] Systemic lupus erythematosus: SLE. A chronic inflammatory connective tissue disease marked by skin rashes, joint pain and swelling, inflammation of the kidneys, inflammation of the fibrous tissue surrounding the heart (i.e., the pericardium), as well as other problems. Not all affected individuals display all of these problems. May be referred to as lupus. [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] Telencephalon: Paired anteriolateral evaginations of the prosencephalon plus the lamina

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terminalis. The cerebral hemispheres are derived from it. Many authors consider cerebrum a synonymous term to telencephalon, though a minority include diencephalon as part of the cerebrum (Anthoney, 1994). [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] Terminator: A DNA sequence sited at the end of a transcriptional unit that signals the end of transcription. [NIH] Testicles: The two egg-shaped glands found inside the scrotum. They produce sperm and male hormones. Also called testes. [NIH] Testosterone: A hormone that promotes the development and maintenance of male sex characteristics. [NIH] Tetani: Causal agent of tetanus. [NIH] Tetanic: Having the characteristics of, or relating to tetanus. [NIH] Tetanus: A disease caused by tetanospasmin, a powerful protein toxin produced by Clostridium tetani. Tetanus usually occurs after an acute injury, such as a puncture wound or laceration. Generalized tetanus, the most common form, is characterized by tetanic muscular contractions and hyperreflexia. Localized tetanus presents itself as a mild condition with manifestations restricted to muscles near the wound. It may progress to the generalized form. [NIH] Tetanus Toxin: The toxin elaborated by Clostridium tetani. It is a protein with a molecular weight of about 150,000, probably consisting of two fragments, tetanolysin being the hemolytic and tetanospasmin the neurotoxic principle. The toxin causes disruption of the inhibitory mechanisms of the CNS, thus permitting uncontrolled nervous activity, leading to fatal convulsions. [NIH] Tetravalent: Pertaining to a group of 4 homologous or partly homologous chromosomes during the zygotene stage of prophase to the first metaphase in meiosis. [NIH] Thalamus: Paired bodies containing mostly gray substance and forming part of the lateral wall of the third ventricle of the brain. The thalamus represents the major portion of the diencephalon and is commonly divided into cellular aggregates known as nuclear groups. [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] Thioguanine: An antineoplastic compound which also has antimetabolite action. The drug is used in the therapy of acute leukemia. [NIH] Thoracic: Having to do with the chest. [NIH] Thorax: A part of the trunk between the neck and the abdomen; 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]

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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] Thromboxanes: Physiologically active compounds found in many organs of the body. They are formed in vivo from the prostaglandin endoperoxides and cause platelet aggregation, contraction of arteries, and other biological effects. Thromboxanes are important mediators of the actions of polyunsaturated fatty acids transformed by cyclooxygenase. [NIH] Thylakoids: Membranous cisternae of the chloroplast containing photosynthetic pigments, reaction centers, and the electron-transport chain. Each thylakoid consists of a flattened sac of membrane enclosing a narrow intra-thylakoid space (Lackie and Dow, Dictionary of Cell Biology, 2nd ed). Individual thylakoids are interconnected and tend to stack to form aggregates called grana. They are found in cyanobacteria and all plants. [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, which helps regulate growth and metabolism. [NIH] Thyroxine: An amino acid of the thyroid gland which exerts a stimulating effect on thyroid metabolism. [NIH] Tinea Pedis: Dermatological pruritic lesion in the feet, caused by Trichophyton rubrum, T. mentagrophytes, or Epidermophyton floccosum. [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] Titre: The quantity of a substance required to produce a reaction with a given volume of another substance, or the amount of one substance required to correspond with a given amount of another substance. [EU] 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] Tonic: 1. Producing and restoring the normal tone. 2. Characterized by continuous tension. 3. A term formerly used for a class of medicinal preparations believed to have the power of restoring normal tone to tissue. [EU] Tonicity: The normal state of muscular tension. [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] Tonsils: Small masses of lymphoid tissue on either side of the throat. [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]

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Torticollis: Wryneck; a contracted state of the cervical muscles, producing twisting of the neck and an unnatural position of the head. [EU] 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] Toxicokinetics: Study of the absorption, distribution, metabolism, and excretion of test substances. [NIH] 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] Toxoid: The material resulting from the treatment of toxin in such a way that the toxic properties are inactivated whilst the antigenic potency remains intact. [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] Traction: The act of pulling. [NIH] Transaminase: Aminotransferase (= a subclass of enzymes of the transferase class that catalyse the transfer of an amino group from a donor (generally an amino acid) to an acceptor (generally 2-keto acid). Most of these enzymes are pyridoxal-phosphate-proteins. [EU]

Transcriptase: An enzyme which catalyses the synthesis of a complementary mRNA 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] Transcutaneous: Transdermal. [EU] 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] 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]

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Translocating: 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] Trigeminal: Cranial nerve V. It is sensory for the eyeball, the conjunctiva, the eyebrow, the skin of face and scalp, the teeth, the mucous membranes in the mouth and nose, and is motor to the muscles of mastication. [NIH] Trismus: Spasmodic contraction of the masseter muscle resulting in forceful jaw closure. This may be seen with a variety of diseases, including tetanus, as a complication of radiation therapy, trauma, or in association with neoplastic conditions. [NIH] Trivalent: Having a valence of three. [EU] Trophic: Of or pertaining to nutrition. [EU] Tropism: Directed movements and orientations found in plants, such as the turning of the sunflower to face the sun. [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] Tryptophan: An essential amino acid that is necessary for normal growth in infants and for nitrogen balance in adults. It is a precursor serotonin and niacin. [NIH] Tubercle: A rounded elevation on a bone or other structure. [NIH] Tuberculin: A sterile liquid containing the growth products of, or specific substances extracted from, the tubercle bacillus; used in various forms in the diagnosis of tuberculosis. [NIH]

Tuberculosis: Any of the infectious diseases of man and other animals caused by species of Mycobacterium. [NIH] Tularemia: A plague-like disease of rodents, transmissible to man. It is caused by Francisella tularensis and is characterized by fever, chills, headache, backache, and weakness. [NIH] Tumor model: A type of animal model which can be 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 or other tissues are called xenograft models. [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] 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

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includes the paratyphoids. [NIH] Tyramine: An indirect sympathomimetic. Tyramine does not directly activate adrenergic receptors, but it can serve as a substrate for adrenergic uptake systems and monoamine oxidase so it prolongs the actions of adrenergic transmitters. It also provokes transmitter release from adrenergic terminals. Tyramine may be a neurotransmitter in some invertebrate nervous systems. [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] Ulcer: A localized necrotic lesion of the skin or a mucous surface. [NIH] 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] Ulnar Nerve: A major nerve of the upper extremity. In humans, the fibers of the ulnar nerve originate in the lower cervical and upper thoracic spinal cord (usually C7 to T1), travel via the medial cord of the brachial plexus, and supply sensory and motor innervation to parts of the hand and forearm. [NIH] Umbilical Arteries: Either of a pair of arteries originating from the internal iliac artery and passing through the umbilical cord to carry blood from the fetus to the placenta. [NIH] Umbilical Cord: The flexible structure, giving passage to the umbilical arteries and vein, which connects the embryo or fetus to the placenta. [NIH] Unconscious: Experience which was once conscious, but was subsequently rejected, as the "personal unconscious". [NIH] Univalent: Pertaining to an unpaired chromosome during the zygotene stage of prophase to first metaphase in meiosis. [NIH] Universal Precautions: Prudent standard preventive measures to be taken by professional and other health personnel in contact with persons afflicted with a communicable disease, to avoid contracting the disease by contagion or infection. Precautions are especially applicable in the diagnosis and care of AIDS patients. [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]

Urinalysis: Examination of urine by chemical, physical, or microscopic means. Routine urinalysis usually includes performing chemical screening tests, determining specific gravity, observing any unusual color or odor, screening for bacteriuria, and examining the sediment microscopically. [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] Urticaria: A vascular reaction of the skin characterized by erythema and wheal formation due to localized increase of vascular permeability. The causative mechanism may be allergy, infection, or stress. [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] Vaccine adjuvant: A substance added to a vaccine to improve the immune response so that less vaccine is needed. [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] Varicella: Chicken pox. [EU] Vas Deferens: The excretory duct of the testes that carries spermatozoa. It rises from the scrotum and joins the seminal vesicles to form the ejaculatory duct. [NIH] Vascular: Pertaining to blood vessels or indicative of a copious blood supply. [EU] Vasculitis: Inflammation of a blood vessel. [NIH] Vasoactive: Exerting an effect upon the calibre of blood vessels. [EU] Vasoconstriction: Narrowing of the blood vessels without anatomic change, for which constriction, pathologic is used. [NIH] 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] Vein: Vessel-carrying blood from various parts of the body to the heart. [NIH] Venereal: Pertaining or related to or transmitted by sexual contact. [EU] 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] Ventilation: 1. In respiratory physiology, the process of exchange of air between the lungs and the ambient air. Pulmonary ventilation (usually measured in litres per minute) refers to the total exchange, whereas alveolar ventilation refers to the effective ventilation of the alveoli, in which gas exchange with the blood takes place. 2. In psychiatry, verbalization of one's emotional problems. [EU] Ventricle: One of the two pumping chambers of the heart. The right ventricle receives oxygen-poor blood from the right atrium and pumps it to the lungs through the pulmonary artery. The left ventricle receives oxygen-rich blood from the left atrium and pumps it to the

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body through the aorta. [NIH] Ventricular: Pertaining to a ventricle. [EU] Vertebrae: A bony unit of the segmented spinal column. [NIH] Vertebral: Of or pertaining to a vertebra. [EU] Vertigo: An illusion of movement; a sensation as if the external world were revolving 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] 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] Viral: Pertaining to, caused by, or of the nature of virus. [EU] Viral Load: The quantity of measurable virus in the blood. Change in viral load, measured in plasma, is used as a surrogate marker in HIV disease progression. [NIH] 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] 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] 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] Virus Latency: The ability of a pathogenic virus to lie dormant within a cell (latent infection). In eukaryotes, subsequent activation and viral replication is thought to be caused by extracellular stimulation of cellular transcription factors. Latency in bacteriophage is maintained by the expression of virally encoded repressors. [NIH] Viscera: Any of the large interior organs in any one of the three great cavities of the body, especially in the abdomen. [NIH] Visceral: , from viscus a viscus) pertaining to a viscus. [EU] Visceral Afferents: The sensory fibers innervating the viscera. [NIH] Vitreous Body: The transparent, semigelatinous substance that fills the cavity behind the crystalline lens of the eye and in front of the retina. It is contained in a thin hyoid membrane and forms about four fifths of the optic globe. [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] Volition: Voluntary activity without external compulsion. [NIH] Voluntary Health Agencies: Non-profit organizations concerned with various aspects of

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health, e.g., education, promotion, treatment, services, etc. [NIH] Vulva: The external female genital organs, including the clitoris, vaginal lips, and the opening to the vagina. [NIH] Warts: Benign epidermal proliferations or tumors; some are viral in origin. [NIH] Wheezing: Breathing with a rasp or whistling sound; a sign of airway constriction or obstruction. [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]

Whooping Cough: A respiratory infection caused by Bordetella pertussis and characterized by paroxysmal coughing ending in a prolonged crowing intake of breath. [NIH] Whooping Cough: A respiratory infection caused by Bordetella pertussis and characterized by paroxysmal coughing ending in a prolonged crowing intake of breath. [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] World Health: The concept pertaining to the health status of inhabitants of the world. [NIH] Wound Healing: Restoration of integrity to traumatized tissue. [NIH] Wound Infection: Invasion of the site of trauma by pathogenic microorganisms. [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] Zoonoses: Diseases of non-human animals that may be transmitted to man or may be transmitted from man to non-human animals. [NIH] Zoster: A virus infection of the Gasserian ganglion and its nerve branches, characterized by discrete areas of vesiculation of the epithelium of the forehead, the nose, the eyelids, and the cornea together with subepithelial infiltration. [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]

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INDEX 3 3-dimensional, 54, 235, 303 A Abdomen, 7, 235, 246, 280, 283, 313, 315, 318, 324 Abdominal, 229, 235, 252, 269, 295, 322 Abdominal Pain, 235, 269, 322 Aberrant, 18, 26, 36, 44, 235 Ablation, 46, 235 Acantholysis, 235, 296 Acatalasia, 235, 248 Acceptor, 179, 235, 271, 283, 295, 320 Acetylcholine, 25, 126, 144, 179, 235, 246, 250, 291, 292 Actin, 235, 287, 289, 290 Acute leukemia, 161, 235, 318 Acute renal, 235, 273 Acyclovir, 20, 235 Acyl, 154, 165, 235 Adaptability, 235, 249 Adaptation, 14, 235, 299 Adenine, 161, 236, 304 Adenocarcinomas, 38, 236 Adenosine, 161, 236, 242, 247, 276, 298 Adenosine Diphosphate, 161, 236 Adenovirus, 43, 67, 236 Adenylate Cyclase, 236, 250, 297 Adjustment, 155, 235, 236 Adjuvant, 9, 11, 20, 21, 28, 29, 48, 53, 60, 100, 102, 123, 130, 151, 172, 175, 183, 236, 238, 269 Adrenal Cortex, 236, 255, 301, 306 Adrenal Glands, 236, 251 Adrenal Medulla, 236, 248, 251, 264, 293, 296 Adrenergic, 156, 236, 260, 264, 316, 322 Adverse Effect, 9, 17, 146, 208, 236, 311 Aerobic, 45, 236, 289, 295, 304 Aerobic Exercise, 45, 236 Aerosol, 236, 316 Aetiology, 85, 236 Affinity, 20, 37, 39, 41, 59, 116, 157, 174, 185, 186, 236, 237, 242, 283, 291, 312 Agar, 237, 299 Agarose, 174, 237 Agonist, 237, 243, 260 Airway, 22, 155, 190, 229, 237, 311, 325 Albumin, 169, 237, 299

Alertness, 237, 247 Algorithms, 5, 237, 245 Alimentary, 237, 296, 297 Alkaline, 34, 237, 238, 243, 247, 298 Alkaloid, 237, 242, 252, 288 Alleles, 169, 237, 274 Allergen, 181, 237, 310 Allogeneic, 16, 37, 49, 237, 272 Allylamine, 237, 238 Alpha Particles, 237, 305 Alternative medicine, 197, 237 Alum, 28, 238, 252 Aluminum, 8, 95, 172, 238 Aluminum Compounds, 8, 238 Aluminum Hydroxide, 172, 238 Alveoli, 238, 323 Amber, 238, 277 Ameliorating, 40, 238 Amination, 150, 238 Amine, 150, 238, 274 Amino Acid Motifs, 238, 254 Amino Acid Sequence, 169, 170, 180, 238, 240, 254, 269, 287, 302 Amino Acid Substitution, 48, 238 Amino Acids, 146, 162, 174, 238, 244, 254, 269, 297, 300, 303, 308, 310, 320, 322 Amino-terminal, 185, 186, 238 Ammonia, 238, 322 Amnion, 239, 250 Amphetamine, 239, 244 Amyloid, 42, 239 Anaerobic, 146, 156, 162, 239, 272, 289, 314 Anaesthesia, 70, 97, 107, 108, 114, 122, 239, 278 Analgesic, 239, 288, 294, 316 Analog, 33, 36, 40, 158, 235, 239 Analogous, 239, 299, 320 Analytes, 239, 316 Anaphylactic, 72, 181, 239 Anaphylatoxins, 239, 253 Anaphylaxis, 72, 239 Anatomical, 23, 154, 239, 245, 262, 277, 289, 309 Androgens, 46, 236, 239 Anemia, 113, 216, 239, 247, 284 Anergy, 74, 239 Anesthesia, 76, 129, 188, 237, 239, 256, 291, 292, 301, 316

328 Tetanus

Anesthetics, 239, 264 Angiotensin converting enzyme inhibitor, 165, 240 Animal model, 11, 15, 39, 40, 52, 57, 58, 65, 161, 240, 321 Anions, 237, 240, 280, 316 Antagonism, 240, 247 Anthrax, 9, 20, 38, 55, 159, 160, 240 Antibacterial, 240, 259, 313 Antibiotic, 5, 7, 159, 240, 257, 260, 313 Antibiotic Prophylaxis, 5, 240 Anticoagulant, 240, 303 Antigen-Antibody Complex, 240, 253 Antigen-presenting cell, 27, 29, 182, 240, 257 Anti-infective, 240, 250, 275, 280 Anti-inflammatory, 54, 240, 241, 270, 278 Anti-Inflammatory Agents, 241 Antimetabolite, 235, 241, 318 Antimicrobial, 43, 241, 258 Antineoplastic, 89, 241, 260, 269, 295, 318 Antioxidant, 241, 295 Antiseptic, 43, 241 Antiserum, 77, 241, 242 Antitoxin, 19, 41, 48, 80, 109, 161, 162, 201, 241 Antiviral, 16, 17, 20, 235, 241, 280, 290, 297 Anus, 241, 242, 246, 306 Anxiety, 55, 241 Apnea, 155, 241 Applicability, 36, 241 Aqueous, 167, 241, 243, 256, 262, 275, 282 Arachidonic Acid, 181, 241, 282, 302 Arginine, 156, 239, 241, 294, 321 Aromatic, 241, 244, 298 Arterial, 237, 241, 247, 303 Arteries, 241, 245, 255, 287, 319, 322 Aspartate, 56, 241 Aspiration, 6, 241 Aspirin, 181, 217, 241 Assay, 3, 9, 12, 38, 64, 71, 77, 171, 172, 241, 277, 321 Astringents, 241, 286 Astrocytes, 44, 156, 241, 242, 270, 291 Astrocytoma, 242, 270 Atmospheric Pressure, 242, 275 Atopic, 79, 242 Atoxic, 143, 153, 242 ATP, 116, 236, 242, 260, 269, 298, 303, 320 Atresia, 4, 242 Atrophy, 41, 235, 242, 291 Atropine, 118, 242, 244

Attenuated, 39, 40, 48, 57, 63, 64, 104, 164, 174, 242, 243, 259 Autacoids, 242, 278 Autoantibodies, 88, 242 Autoantigens, 242 Autoimmune disease, 40, 242, 289 Autoimmunity, 4, 59, 242 Autologous, 13, 27, 29, 46, 172, 242 Autologous tumor cells, 13, 242 Autonomic, 74, 83, 122, 235, 242, 244, 256, 270, 290, 293, 297, 312, 316 Autonomic Nervous System, 83, 242, 244, 297, 312, 316 Autopsy, 142, 242 Avidity, 32, 65, 95, 242 Axonal, 39, 50, 59, 154, 171, 242 Axons, 59, 243, 258, 280, 294, 301, 305, 307 B Bacillus, 63, 64, 240, 243, 246, 321 Baclofen, 70, 94, 243 Bacteremia, 28, 161, 243 Bacterial Infections, 24, 243 Bacterial Physiology, 236, 243 Bacterial toxin, 38, 47, 149, 167, 175, 241, 243 Bacterial Vaccines, 61, 151, 243 Bactericidal, 32, 61, 64, 84, 243, 265 Bacteriophage, 65, 243, 299, 320, 324 Bacterium, 146, 179, 243, 254, 273, 319, 321 Bacteriuria, 243, 322 Barium, 116, 243 Basal Ganglia, 54, 243, 261, 268, 270, 305 Base, 13, 19, 59, 79, 236, 243, 257, 268, 269, 281, 288, 296, 297, 298, 305, 318, 321 Basement Membrane, 243, 265 Basophils, 180, 181, 243, 272, 282 Belladonna, 242, 244 Benign, 30, 244, 268, 272, 290, 325 Beta-pleated, 239, 244 Bile, 244, 268, 273, 275, 281, 283, 314 Bile Pigments, 244, 281 Biliary, 244, 273 Bilirubin, 237, 244, 276 Binding Sites, 42, 244 Bioassay, 244 Bioavailability, 20, 36, 244 Bioavailable, 20, 244 Biochemical, 37, 38, 51, 59, 75, 116, 129, 237, 241, 244, 267, 271, 282, 310 Biogenic Amines, 129, 244 Biological Assay, 41, 244 Biological response modifier, 244, 279

Index 329

Biological therapy, 244, 272 Biological Transport, 244, 259 Biomolecular, 41, 156, 244, 316 Biopsy, 245, 314 Biosynthesis, 36, 241, 245, 303, 310 Biotechnology, 62, 68, 86, 123, 148, 189, 197, 207, 244, 245 Bioterrorism, 20, 245 Biotransformation, 245 Biotype, 245, 272 Biphasic, 25, 245 Bivalent, 73, 245 Bladder, 245, 278, 289, 302, 303, 322, 323 Blastocyst, 245, 254, 298 Blepharospasm, 144, 180, 245 Blister, 245, 296 Blood Coagulation, 245, 247, 319 Blood Glucose, 245, 273, 276, 279 Blood Platelets, 245, 310, 318 Blood pressure, 11, 181, 216, 245, 247, 276, 288, 312 Blot, 12, 245 Body Fluids, 41, 214, 215, 245, 260, 312 Body Regions, 245, 252 Bone Marrow, 15, 29, 61, 96, 235, 245, 246, 276, 284, 312, 314, 315 Bone Marrow Transplantation, 29, 96, 246 Bone scan, 246, 309 Botulinum Toxins, 172, 179, 180, 246 Bowel, 246, 259, 263, 278, 280, 282, 322 Bowel Movement, 246, 259 Brachial, 246, 322 Brachial Plexus, 246, 322 Brain Hypoxia, 168, 246 Brain Stem, 60, 246 Branch, 227, 246, 261, 269, 284, 296, 304, 312, 318 Breakdown, 42, 246, 259, 268, 294 Breast Feeding, 30, 246 Bronchi, 246, 264, 320 Bronchial, 246, 274 Bronchiseptica, 246, 297 Buccal, 246, 284 Buffers, 56, 246 Bupivacaine, 97, 246, 282 Burns, 71, 132, 161, 190, 246 Burns, Electric, 246 C Cadmium, 35, 247 Cadmium Poisoning, 247 Caffeine, 122, 247, 304

Calcium, 34, 51, 122, 123, 181, 184, 185, 247, 253, 281, 308, 311 Calcium Channels, 34, 247 Cancer vaccine, 36, 61, 138, 247, 286 Capsules, 247, 269, 270 Captopril, 165, 247 Carbohydrate, 36, 247, 271, 300 Carbon Dioxide, 247, 257, 267, 268, 298, 307 Carboxy, 100, 162, 185, 186, 247 Carboxymethylcellulose, 53, 247 Carboxy-terminal, 185, 186, 247 Carcinoembryonic Antigen, 159, 160, 247 Carcinogenic, 247, 279, 302, 314 Carcinogens, 248, 251 Carcinoma, 37, 142, 247, 248 Cardiac, 12, 74, 89, 107, 237, 247, 248, 259, 261, 262, 264, 269, 282, 290, 314, 315 Cardiac Output, 248, 315 Cardiorespiratory, 236, 248 Cardiovascular, 11, 122, 239, 247, 248, 282, 310, 312 Carotene, 248, 307 Case report, 66, 101, 104, 112, 118, 129, 248, 251, 266 Case series, 248, 251 Castor Oil, 248, 308 Catalase, 168, 235, 248 Catalyse, 248, 320 Catecholamine, 83, 116, 118, 248, 260 Cathode, 248, 256, 261 Cations, 248, 280 Caudate Nucleus, 248, 255, 291 Caveolae, 12, 248 Caveolins, 248 Cell Adhesion, 50, 248 Cell Count, 16, 249 Cell Cycle, 59, 249, 304 Cell Death, 42, 249, 290 Cell Differentiation, 249, 311 Cell Division, 243, 249, 272, 286, 287, 299, 302 Cell membrane, 47, 168, 181, 244, 247, 248, 249, 258, 265, 268, 286 Cell Membrane Structures, 248, 249 Cell Physiology, 42, 249 Cell proliferation, 26, 172, 249, 311 Cell Respiration, 249, 295, 307 Cell Size, 249, 267 Cell Survival, 249, 272 Cell Transplantation, 29, 249 Cellular Structures, 249, 288

330 Tetanus

Centrifugation, 145, 249, 317 Cerebral, 41, 156, 180, 243, 246, 249, 255, 264, 265, 267, 270, 280, 285, 296, 305, 312, 318 Cerebral hemispheres, 243, 246, 249, 270, 318 Cerebral Palsy, 180, 249, 312 Cerebrum, 249, 318 Cervical, 180, 246, 250, 320, 322 Cervix, 250 Character, 173, 250, 257 Chemotactic Factors, 250, 253 Chemotherapeutics, 39, 250 Chemotherapy, 29, 46, 61, 138, 250 Chickenpox, 214, 250 Child Care, 4, 250 Chimeras, 12, 250 Chimeric Proteins, 22, 250 Chlorhexidine, 43, 250 Chlorophyll, 250, 263 Chloroplasts, 64, 250 Cholera, 5, 9, 24, 38, 47, 164, 167, 172, 175, 178, 250, 310, 324 Cholera Toxin, 9, 24, 47, 164, 167, 175, 250 Cholesterol, 48, 216, 244, 248, 250, 259, 283, 314 Choline, 41, 46, 250 Cholinergic, 46, 116, 156, 180, 246, 250, 289 Chorioamnionitis, 28, 250 Chorion, 250, 251 Choroid, 251, 307 Chromaffin Cells, 51, 116, 118, 251, 296 Chromaffin Granules, 116, 251 Chromatin, 251, 263, 292, 313 Chromic, 251 Chromium, 9, 122, 251 Chromosomal, 54, 251 Chromosome, 251, 254, 283, 321, 322 Chronic prostatitis, 3, 251 Chymopapain, 251, 295 Circadian, 50, 251 CIS, 251, 307 Clamp, 12, 32, 251 Clear cell carcinoma, 251, 258 Cleave, 13, 33, 184, 185, 251 Clinical Medicine, 251, 301 Clinical study, 29, 60, 189, 190, 251 Clinical trial, 8, 11, 14, 18, 19, 21, 41, 43, 44, 137, 139, 207, 251, 255, 303, 305 Clone, 38, 252 Clonic, 245, 252 Cloning, 37, 63, 103, 245, 252

Clot Retraction, 252, 299 Coagulation, 54, 245, 252, 273, 299 Coca, 252 Cocaine, 31, 252 Cod Liver Oil, 252, 262 Cofactor, 252, 303, 319 Cognition, 56, 252 Colic, 30, 252, 287 Colitis, 5, 54, 252 Collagen, 58, 243, 252, 266, 269, 302 Collapse, 229, 239, 246, 252, 311 Colloidal, 237, 252, 261, 297, 316 Colonoscopy, 48, 252 Colorectal, 37, 252 Combinatorial, 9, 253 Communicable disease, 219, 253, 322 Communis, 248, 253, 308 Complement, 54, 143, 239, 253, 269, 284, 299, 310 Complement Activation, 54, 239, 253 Complementary and alternative medicine, 121, 134, 253 Complementary medicine, 121, 253 Computational Biology, 207, 253 Computed tomography, 253, 254, 309 Computerized axial tomography, 253, 254, 309 Conception, 254, 255, 266, 314 Concomitant, 80, 254 Cones, 254, 307 Conjugation, 153, 154, 178, 245, 254 Conjunctiva, 254, 279, 321 Conjunctivitis, 181, 254 Connective Tissue, 246, 252, 254, 266, 268, 269, 284, 287, 308, 317 Consciousness, 239, 254, 257, 260 Consensus Sequence, 61, 238, 254 Conserved Sequence, 238, 254 Consultation, 208, 254 Consumption, 254, 258, 269, 295 Contamination, 164, 176, 219, 254, 308 Contraceptive, 24, 142, 255 Contracture, 116, 122, 255, 283 Contraindications, ii, 215, 255 Contralateral, 54, 255 Contrast Media, 181, 255 Control group, 30, 43, 45, 255 Controlled study, 69, 255 Convulsion, 230, 244, 255 Convulsive, 255, 262, 291, 292 Coordination, 255, 289 Cornea, 255, 325

Index 331

Coronary, 255, 287 Coronary Thrombosis, 255, 287 Corpus, 156, 255, 270, 291, 296, 301 Corpus Striatum, 156, 255, 270, 291 Cortex, 156, 255, 263, 265, 267, 280, 295, 305 Cortical, 117, 156, 255, 265, 305, 309 Corticosteroids, 255, 270 Cortisol, 50, 237, 255 Cortisone, 217, 255 Cranial, 111, 190, 255, 256, 270, 272, 294, 297, 313, 321 Cranial Nerve Injuries, 190, 256 Cranial Nerves, 256 Craniocerebral Trauma, 256, 273, 319 Creatine, 41, 256 Creatinine, 256 Crotoxin, 58, 256 Crystallization, 58, 256 Curare, 256, 289 Curative, 256, 318 Cutaneous, 103, 240, 256, 284, 313 Cyclic, 236, 247, 256, 302, 309 Cysteine, 170, 251, 256, 260, 263 Cystine, 256, 260 Cytokine, 17, 18, 19, 26, 31, 32, 38, 48, 53, 59, 62, 78, 159, 160, 256 Cytomegalovirus, 17, 256 Cytoplasm, 168, 244, 249, 250, 256, 263, 272, 292, 308, 317 Cytotoxic, 9, 18, 21, 29, 59, 130, 182, 217, 256, 311 Cytotoxicity, 18, 38, 237, 256, 281 D Data Display, 20, 256 Databases, Bibliographic, 207, 257 Daunorubicin, 257, 260 De novo, 15, 257 Deamination, 257, 322 Decarboxylation, 244, 257, 274 Decidua, 257, 298 Degenerative, 38, 39, 168, 257, 270, 273, 289 Dehydration, 250, 257 Dehydroepiandrosterone, 130, 257 Deletion, 175, 257 Dementia, 44, 257 Dendrites, 15, 23, 46, 257, 258, 292, 305 Dendritic, 15, 21, 22, 23, 29, 37, 45, 46, 49, 50, 79, 257, 286, 307 Dendritic cell, 15, 21, 22, 29, 37, 46, 49, 79, 257

Dendritic cell vaccine, 22, 257 Density, 23, 50, 143, 249, 257, 267, 283, 289, 294, 300 Dental Caries, 56, 257 Dentate Gyrus, 56, 257, 274 Dentifrices, 238, 258 Depolarization, 163, 258, 291, 292, 311 Deprivation, 117, 258 Dermatitis, 258, 261 Dermatomycoses, 7, 258 DES, 188, 239, 258 Detergents, 142, 258 Deuterium, 258, 275 Developed Countries, 38, 60, 147, 170, 258 Developing Countries, 39, 60, 111, 151, 178, 258 Dextrans, 181, 258 Diabetes Insipidus, 190, 258 Diabetes Mellitus, 28, 258, 271, 273 Diabetic Foot, 87, 258 Diagnostic procedure, 141, 197, 258 Dialyzer, 258, 273 Diamines, 167, 258 Diarrhea, 30, 54, 258, 263, 281, 287 Diffusion, 144, 244, 259, 278 Digestion, 40, 237, 244, 246, 259, 280, 283, 297, 315, 323 Digestive system, 139, 259 Digestive tract, 259, 311, 313, 314 Digitonin, 116, 259 Dilatation, 259, 301 Dilution, 18, 259, 299 Dimethyl, 163, 259 Diphtheria Toxin, 19, 22, 48, 113, 149, 167, 168, 259 Diphtheria-Tetanus Vaccine, 69, 72, 81, 259 Diphtheria-Tetanus-acellular Pertussis Vaccines, 85, 94, 95, 102, 103, 259 Diphtheria-Tetanus-Pertussis Vaccine, 79, 107, 126, 259 Direct, iii, 4, 12, 24, 27, 39, 44, 161, 175, 199, 251, 259, 260, 306, 314, 317 Disease Progression, 41, 42, 259, 324 Disinfectant, 250, 259, 265 Disinfection, 219, 259 Dissociation, 74, 236, 259 Dissociative Disorders, 260 Distal, 243, 260, 261, 301, 304 Disulphide, 185, 260 Diuresis, 247, 260 Diuretic, 260, 285, 312

332 Tetanus

Diurnal, 50, 55, 260 DNA Topoisomerase, 260, 269 Dopamine, 14, 54, 239, 252, 260, 298 Doxorubicin, 20, 260 Drive, ii, vi, 115, 152, 195, 217, 260, 282 Drug Interactions, 201, 260 Drug Tolerance, 260, 319 Duct, 34, 260, 308, 323 Dura mater, 260, 286, 295 Dyes, 46, 239, 244, 260, 267, 292 Dynorphins, 261, 294 Dyskinesias, 261, 289 Dysphagia, 78, 230, 261 Dysphonia, 144, 180, 261 Dyspnea, 170, 261 Dystonia, 180, 261 E Eating Disorders, 57, 261 Eczema, 30, 261 Edema, 7, 19, 55, 181, 261, 281 Effector, 58, 181, 235, 253, 261, 281, 292 Effector cell, 261, 281, 292 Ejaculation, 34, 261, 310 Elastin, 252, 261 Electrocoagulation, 252, 261 Electrode, 35, 248, 261 Electrolyte, 261, 300, 312 Electrons, 241, 243, 248, 261, 280, 295, 305, 316 Electrophoresis, 129, 170, 261, 281 Electrophysiological, 23, 54, 78, 261 Electroshock, 262, 291, 292 Elementary Particles, 261, 262, 292, 303 Embryo, 239, 245, 249, 262, 278, 300, 322 Emollient, 262, 288 Empirical, 45, 262 Emulsion, 151, 262, 267 Enamel, 257, 262 Encapsulated, 158, 262 Encephalitis, 68, 176, 262 Encephalitis, Viral, 262 Encephalomyelitis, 40, 59, 262 Endemic, 154, 178, 250, 262, 284, 313 Endocarditis, 6, 28, 214, 262 Endocardium, 262 Endocytosis, 15, 67, 248, 262 Endometrium, 257, 262, 286 Endopeptidases, 263, 303 Endorphins, 263, 294, 302 Endothelial cell, 13, 58, 262, 263, 319 Endotoxin, 161, 263, 321 Enkephalin, 56, 263, 302

Enteric bacteria, 40, 263 Enterocolitis, 30, 263 Enteropeptidase, 263, 321 Enterotoxins, 19, 174, 263 Entorhinal Cortex, 263, 274 Environmental Health, 85, 206, 208, 263 Environmental Pollutants, 35, 263 Enzymatic, 34, 39, 48, 56, 165, 168, 181, 244, 247, 248, 253, 257, 263, 274, 295, 307 Enzyme-Linked Immunosorbent Assay, 64, 77, 263 Eosinophilic, 30, 263 Eosinophilic Gastroenteritis, 30, 263 Eosinophils, 263, 272, 282 Epidemic, 20, 154, 177, 178, 264, 313 Epidemiological, 31, 119, 124, 131, 189, 264, 266 Epidermal, 160, 172, 264, 286, 325 Epidermal Growth Factor, 172, 264 Epidermis, 235, 245, 264, 296, 305 Epidermoid carcinoma, 172, 264, 313, 314 Epidural, 76, 97, 264 Epiglottis, 264 Epiglottitis, 158, 264 Epinephrine, 50, 236, 244, 251, 260, 264, 293, 322 Epithelial, 22, 30, 35, 38, 49, 63, 172, 236, 244, 250, 257, 264, 273 Epithelial Cells, 22, 30, 35, 49, 63, 236, 250, 264, 273 Epithelium, 243, 264, 269, 296, 325 Epitope, 10, 22, 38, 83, 154, 159, 160, 162, 169, 177, 264 Erectile, 264, 296 Erysipelas, 7, 264 Erythema, 264, 323 Erythrasma, 7, 264 Erythrocytes, 239, 246, 264, 306, 310 Esophagus, 242, 259, 265, 298, 315 Esotropia, 265, 315 Estrogens, 265, 271 Ethanol, 25, 26, 265, 266 Ethnic Groups, 48, 265 Evoke, 22, 161, 265, 314 Excitation, 23, 156, 265, 267 Excitatory, 23, 44, 50, 56, 243, 265, 271 Excitotoxicity, 39, 44, 265 Exhaustion, 240, 265, 284 Exocytosis, 35, 112, 118, 181, 184, 185, 265, 317 Exogenous, 24, 64, 159, 160, 168, 245, 247, 261, 265, 303

Index 333

Exotoxin, 149, 161, 265 Exotropia, 265, 315 Expiration, 265, 307 External radiation, 265, 314 Extracellular, 12, 51, 54, 161, 239, 242, 254, 262, 265, 266, 291, 312, 324 Extracellular Matrix, 55, 254, 265, 266 Extracellular Space, 12, 51, 265 Extraction, 129, 152, 266 Extrapyramidal, 260, 266 Extremity, 246, 266, 322 Eye Infections, 236, 266 F Facial, 5, 76, 85, 156, 187, 256, 266, 312 Facial Pain, 187, 266 Family Planning, 207, 266 Fat, 241, 246, 248, 266, 283, 289, 290, 294, 308, 312, 316 Fatal Outcome, 266, 290, 305 Fatigue, 152, 266, 273 Fatty acids, 237, 266, 283, 302, 308, 319 Febrile, 17, 104, 266, 284, 285 Feces, 170, 247, 266 Fermentation, 11, 266 Fetal Blood, 250, 266 Fetus, 124, 147, 250, 266, 267, 298, 322, 323 Fever of Unknown Origin, 6, 266 Fibrin, 245, 252, 266, 299, 318 Fibroblasts, 10, 266 Fibrosis, 7, 237, 255, 266, 309 Filtration, 143, 168, 266 Firearms, 216, 266 Fissure, 253, 257, 267 Fixation, 267, 310 Flaccid, 144, 155, 267 Flow Cytometry, 9, 31, 32, 47, 62, 267, 277 Fluorescence, 12, 47, 180, 267 Fluorescent Dyes, 267 Foetal, 93, 267 Fold, 16, 39, 164, 267 Follicles, 15, 267 Folliculitis, 7, 267 Food Hypersensitivity, 30, 267 Food Packaging, 172, 267 Foot Ulcer, 258, 268 Forearm, 245, 268, 322 Fractionation, 167, 268, 317 Frameshift, 268, 321 Frameshift Mutation, 268, 321 Fructose, 268, 271, 280 Fungi, 7, 254, 258, 266, 268, 287, 289, 313, 325

G Gallbladder, 235, 244, 259, 268 Ganglia, 235, 268, 291, 296, 297, 316 Ganglion, 268, 307, 325 Ganglioside, 47, 58, 135, 268 Gangrene, 6, 235, 268 Gangrenous, 268, 310 Gap Junctions, 268, 317 Gas, 12, 238, 247, 259, 268, 275, 292, 307, 316, 323 Gas exchange, 268, 307, 323 Gastric, 38, 238, 264, 268, 269, 274, 275, 297 Gastric Juices, 268, 297 Gastric Mucosa, 269, 297 Gastrin, 269, 274 Gastritis, 6, 269 Gastroenteritis, 269, 308 Gastrointestinal, 40, 247, 264, 265, 267, 269, 281, 282, 285, 310, 312, 315, 324 Gastrointestinal tract, 247, 265, 269, 281, 282, 310 Gelatin, 87, 269, 271, 316, 318 Gene, 11, 18, 44, 46, 52, 53, 54, 57, 67, 73, 146, 159, 167, 181, 189, 236, 237, 245, 269, 283, 299 Gene Fusion, 181, 269 General practitioner, 95, 269 Generator, 155, 269 Genetic Code, 269, 293 Genetic Engineering, 245, 252, 269 Genetics, 44, 52, 254, 269, 288 Genistein, 34, 269 Genital, 24, 251, 269, 323, 325 Genotype, 245, 269, 298 Geriatric, 110, 269 Germ Cells, 269, 286, 295, 312, 313 Germinal Center, 15, 269 Gestation, 62, 270, 297, 298 Gland, 46, 236, 255, 270, 284, 285, 295, 302, 303, 309, 314, 315, 319 Glioblastoma, 172, 270 Glioblastoma multiforme, 172, 270 Gliosis, 40, 270 Globus Pallidus, 255, 270, 305 Glomerular, 168, 270, 280, 285, 306 Glomerular Filtration Rate, 270, 285 Glomeruli, 270 Glomerulonephritis, 143, 270 Glomerulus, 270 Glossopharyngeal Nerve, 266, 270 Glottis, 270, 297 Glucans, 57, 270

334 Tetanus

Glucocorticoid, 50, 270 Glucose, 117, 245, 251, 258, 270, 271, 273, 279, 305, 308, 312 Glucose Intolerance, 258, 271 Glucosyltransferases, 56, 271 Glucuronic Acid, 271, 273 Glutamate, 14, 39, 44, 51, 265, 271, 287 Glutamic Acid, 271, 302 Glycine, 174, 271, 310 Glycols, 271, 275 Glycoprotein, 160, 247, 271, 317, 319, 321 Glycoside, 259, 271, 308 Glycosidic, 271, 293 Glycosylation, 36, 271 Gonadal, 271, 314 Gonadotropic, 142, 271 Gonadotropin, 142, 177, 271 Gonads, 271, 296 Gonorrhea, 219, 271 Governing Board, 271, 301 Gp120, 271, 297 Grade, 270, 271 Graft, 29, 69, 272, 275, 277 Graft Rejection, 272, 277 Grafting, 37, 272 Gram-negative, 146, 246, 272, 289, 304, 324 Gram-positive, 146, 272, 289, 314, 315 Granule, 181, 257, 272, 308 Granulocytes, 272, 282, 311, 325 Granulomas, 151, 272 Growth factors, 129, 172, 272 H Habitat, 272, 289 Habitual, 250, 272 Hair follicles, 267, 272, 314 Half-Life, 147, 272 Handwashing, 219, 272 Haptens, 146, 236, 272 Headache, 247, 272, 279, 321 Health Behavior, 55, 273 Health Promotion, 82, 273 Health Status, 7, 31, 49, 273, 300, 325 Heart failure, 217, 273 Hemodialysis, 68, 79, 119, 131, 258, 273, 281 Hemoglobin, 239, 265, 273 Hemolytic, 54, 113, 162, 273, 277, 318 Hemorrhage, 190, 256, 261, 273, 308, 315 Hemostasis, 273, 310 Heparin, 169, 181, 273 Hepatic, 62, 237, 273 Hepatobiliary, 6, 273

Hepatocytes, 273 Hereditary, 54, 274, 289, 291, 299 Heredity, 269, 274 Herpes, 52, 219, 235, 274 Herpes Zoster, 274 Heterogeneity, 88, 237, 274 Heterogenic, 274 Heterogenous, 157, 274 Heterotrophic, 268, 274 Heterotropia, 274, 315 Hippocampus, 23, 34, 257, 274, 305, 315 Histamine, 181, 239, 244, 274 Histidine, 274 Homeostasis, 54, 274, 312 Homogeneous, 149, 274 Homologous, 55, 59, 66, 67, 150, 157, 237, 245, 274, 289, 310, 317, 318, 321 Homozygote, 113, 274 Hormonal, 49, 242, 244, 251, 274 Hormone, 142, 168, 177, 217, 244, 255, 258, 264, 269, 274, 279, 280, 286, 301, 308, 309, 311, 318, 319 Hormone Replacement Therapy, 217, 274 Horseradish Peroxidase, 263, 274 Hospitals, Public, 274, 276 Humoral, 18, 22, 29, 37, 40, 60, 62, 64, 89, 160, 272, 275 Humour, 275 Hybrid, 12, 39, 42, 65, 94, 122, 149, 167, 168, 180, 181, 182, 252, 275 Hybridization, 148, 149, 275, 288 Hybridoma, 153, 275 Hydrochloric Acid, 275, 296 Hydrogen, 168, 235, 238, 243, 246, 247, 248, 258, 275, 283, 288, 292, 293, 295, 303, 316 Hydrogen Peroxide, 168, 248, 275, 283, 316 Hydrolysis, 245, 275, 298, 300, 303, 321 Hydrophilic, 20, 258, 275 Hydrophobic, 165, 258, 275, 283 Hydroxides, 275 Hydroxyl Radical, 168, 275 Hydroxylamine, 152, 275 Hydroxylysine, 252, 275 Hydroxyproline, 252, 275 Hygienic, 43, 275 Hyperaemia, 254, 275 Hyperbaric, 123, 124, 125, 275 Hyperbaric oxygen, 123, 124, 125, 275 Hyperbilirubinemia, 276, 281 Hyperhidrosis, 180, 276

Index 335

Hypersensitivity, 11, 30, 31, 45, 237, 239, 276, 277, 282, 287, 308, 310, 311 Hypoglycemia, 50, 276 Hypoglycemic, 50, 276 Hypotension, 30, 230, 276 Hypothalamic, 50, 142, 276 Hypothalamus, 242, 263, 276, 302 Hypothermia, 276, 290 Hypoxanthine, 148, 276 I Id, 119, 132, 220, 226, 228, 276 Imaging procedures, 276, 320 Immune adjuvant, 238, 276 Immune function, 11, 16, 45, 276 Immune Sera, 276 Immunization Programs, 149, 157, 276 Immunization Schedule, 188, 277 Immunoassay, 172, 263, 277 Immunochemistry, 148, 277 Immunocompromised, 53, 277 Immunocompromised Host, 53, 277 Immunodeficiency, 27, 28, 65, 104, 208, 214, 215, 218, 219, 277 Immunodeficiency syndrome, 214, 219, 277 Immunogen, 22, 25, 162, 177, 277 Immunoglobulin, 64, 65, 69, 89, 94, 105, 123, 142, 147, 196, 240, 277, 288 Immunologic, 10, 11, 17, 30, 31, 64, 79, 84, 92, 93, 100, 126, 173, 178, 250, 276, 277 Immunologic Memory, 79, 92, 277 Immunologic Tests, 31, 277 Immunomodulator, 9, 31, 277 Immunophenotyping, 10, 18, 19, 277 Immunosuppressive, 26, 270, 277 Immunosuppressive therapy, 277 Immunotherapy, 17, 21, 29, 37, 46, 61, 149, 172, 244, 277 Impairment, 17, 23, 32, 41, 42, 147, 158, 217, 261, 266, 277, 286 Impetigo, 7, 277 Incision, 278, 280 Incontinence, 278, 289 Incubation, 278, 297 Incubation period, 278, 297 Indicative, 188, 278, 296, 323 Indomethacin, 117, 278 Induction, 27, 30, 34, 38, 49, 56, 93, 154, 181, 239, 262, 278 Infancy, 23, 51, 62, 64, 84, 88, 94, 102, 278 Infant Mortality, 131, 278 Infantile, 146, 278

Infarction, 255, 278, 287, 307 Infectious Mononucleosis, 278, 288 Infertility, 142, 278 Infiltration, 270, 278, 301, 325 Inflammatory bowel disease, 5, 278 Influenza, 5, 45, 46, 93, 130, 137, 151, 152, 153, 159, 160, 175, 215, 216, 217, 219, 279 Infusion, 118, 279 Ingestion, 240, 247, 279, 299 Inguinal, 276, 279 Inhalation, 22, 61, 236, 279, 299, 313 Initiation, 4, 29, 50, 55, 279, 320 Initiator, 244, 279 Inlay, 279, 307 Inner ear, 279, 296 Innervation, 246, 279, 322 Inorganic, 238, 275, 279, 289 Inositol, 279, 287, 309 Inotropic, 260, 279 Insight, 182, 279 Insulator, 279, 289 Insulin, 20, 126, 244, 279 Insulin-dependent diabetes mellitus, 279 Intensive Care, 70, 76, 89, 101, 131, 147, 279 Interferon, 117, 279 Interferon-alpha, 279 Interleukin-2, 119, 131, 137, 138, 280 Intermittent, 131, 162, 280, 283 Internal Capsule, 255, 280 Interneurons, 46, 56, 280 Interstitial, 265, 280, 286, 306 Intestinal, 30, 48, 54, 248, 250, 263, 280, 290 Intestine, 246, 280, 282, 315 Intoxication, 59, 162, 280, 325 Intracellular Membranes, 280, 286 Intramuscular, 39, 62, 114, 129, 144, 180, 181, 215, 280, 296 Intramuscular injection, 39, 62, 114, 144, 180, 181, 280 Intrathecal, 69, 70, 94, 196, 280 Intravenous, 31, 41, 214, 279, 280, 296 Intrinsic, 54, 144, 237, 243, 280 Inulin, 20, 270, 280 Invalidate, 55, 280 Invasive, 35, 40, 44, 158, 159, 276, 280, 284 Involuntary, 144, 255, 261, 280, 290, 306, 312 Iodine, 123, 280 Ion Channels, 12, 242, 280, 291, 292, 317 Ions, 51, 243, 246, 247, 260, 261, 275, 280, 281, 288, 308

336 Tetanus

Ipsilateral, 54, 281 Ischemia, 242, 268, 281, 289, 307 Isoelectric, 168, 170, 281 Isoelectric Focusing, 170, 281 Isoelectric Point, 168, 170, 281 J Jaundice, 214, 276, 281 Joint, 6, 208, 281, 316, 317 K Kb, 206, 281 Keratolytic, 257, 281 Keto, 281, 320 Keyhole, 16, 21, 281 Keyhole limpet hemocyanin, 16, 281 Kidney Failure, 281, 285 Kidney Transplantation, 7, 281 Killer Cells, 281 Kinetic, 33, 47, 281 L Labile, 48, 175, 253, 281 Laceration, 78, 281, 318 Lactose Intolerance, 281, 287 Lanthanum, 118, 281 Large Intestine, 259, 263, 280, 282, 306, 311 Laryngeal, 181, 282 Larynx, 264, 270, 282, 320 Latent, 17, 45, 282, 324 Laxative, 237, 247, 282, 288, 312 Lectin, 282, 286 Lens, 247, 282, 324 Lesion, 41, 54, 268, 270, 282, 283, 319, 322 Lethal, 19, 23, 55, 73, 90, 157, 160, 172, 180, 243, 259, 282, 308 Leucocyte, 143, 148, 282 Leukemia, 260, 282 Leukocytes, 18, 243, 246, 250, 263, 272, 278, 279, 282, 292, 321 Leukotrienes, 181, 241, 282 Libido, 239, 282 Library Services, 226, 282 Lidocaine, 114, 282 Life cycle, 245, 268, 282 Ligament, 282, 303 Ligands, 42, 52, 282, 316 Linkage, 44, 150, 165, 283 Lipid, 53, 66, 185, 186, 248, 250, 279, 281, 283, 289, 295 Lipid Peroxidation, 283, 295 Lipophilic, 156, 283 Lipopolysaccharide, 52, 66, 67, 160, 177, 178, 272, 283 Lipoprotein, 272, 283

Liposomes, 118, 151, 168, 283 Lipoxygenase, 282, 283 Liver cancer, 214, 283 Liver scan, 283, 309 Liver Transplantation, 69, 283 Localization, 12, 283 Localized, 96, 144, 153, 154, 257, 259, 262, 267, 276, 278, 283, 289, 295, 299, 318, 322, 323 Lockjaw, 162, 217, 283 Locomotion, 25, 283, 299 Locomotor, 25, 283 Longitudinal Studies, 6, 283 Long-Term Care, 110, 283 Long-Term Potentiation, 34, 56, 283 Lumen, 34, 284 Lupus, 217, 284, 317 Lymph, 15, 250, 263, 275, 278, 284, 315 Lymph node, 15, 250, 284 Lymphatic, 278, 284, 287, 312, 313, 319 Lymphatic system, 284, 312, 313, 319 Lymphocyte, 3, 9, 15, 18, 26, 31, 97, 149, 240, 281, 284, 285 Lymphocytic, 31, 284 Lymphocytosis, 284, 297 Lymphoid, 240, 255, 269, 282, 284, 319 Lysine, 156, 167, 275, 284, 321 M Macrophage, 32, 61, 143, 284 Magnetic Resonance Imaging, 284, 309 Major Histocompatibility Complex, 169, 284 Malaria, 93, 97, 160, 164, 177, 284, 285 Malaria, Falciparum, 284, 285 Malaria, Vivax, 284, 285 Malignancy, 13, 142, 149, 285, 296 Malignant, 156, 172, 236, 241, 270, 283, 285, 290 Malignant tumor, 172, 236, 285 Malnutrition, 237, 242, 285 Mammogram, 8, 285 Mammography, 48, 285 Manifest, 243, 285, 315 Mannitol, 20, 285 Masseter Muscle, 285, 321 Mastication, 6, 285, 321 Mastitis, 285, 310 Mastocyte, 180, 285 Maxillofacial Injuries, 190, 285 Measles Virus, 177, 285 Measles-Mumps-Rubella Vaccine, 73, 285 Meat, 156, 285

Index 337

Medial, 265, 270, 285, 313, 322 Mediate, 13, 26, 130, 184, 185, 260, 281, 285 Mediator, 26, 280, 285, 310 Medical Records, 285, 308 MEDLINE, 207, 285 Medullary, 14, 286, 305 Meiosis, 245, 286, 289, 317, 318, 322 Melanin, 286, 298, 322 Melanocytes, 286 Melanoma, 13, 36, 37, 100, 286 Melanoma vaccine, 100, 286 Membrane Fusion, 13, 184, 185, 286 Membrane Proteins, 154, 248, 283, 286, 303 Memory, 10, 13, 14, 15, 23, 25, 33, 41, 42, 59, 62, 81, 126, 257, 270, 284, 286 Meninges, 249, 256, 260, 286 Meningitis, 6, 28, 147, 154, 157, 158, 190, 272, 286 Meningococcal Vaccines, 164, 286 Menstrual Cycle, 24, 49, 286, 301 Menstruation, 257, 286 Mental Disorders, 140, 286, 301, 304 Mental Health, iv, 8, 140, 206, 209, 286, 293, 301, 304 Mental Processes, 260, 286, 304 Mercury, 35, 267, 286 Merozoite Surface Protein 1, 100, 287 Mesenchymal, 58, 264, 287 Metabolic disorder, 258, 287 Metabolite, 245, 259, 287 Metabotropic, 14, 287 Metaphase, 245, 287, 318, 322 Metastasis, 21, 287 Metastatic, 13, 21, 29, 142, 287, 309 Metastatic cancer, 21, 142, 287 Methionine, 259, 287, 302 MI, 81, 95, 233, 287 Microbe, 156, 287, 320 Microbiology, 19, 21, 71, 75, 82, 90, 102, 108, 109, 113, 117, 126, 236, 243, 287 Microfilaments, 127, 287 Microorganism, 182, 252, 287, 296, 324 Micro-organism, 257, 287, 310 Microscopy, 12, 243, 274, 287 Microtubules, 127, 287, 295 Migration, 59, 287, 291 Milk Hypersensitivity, 30, 287 Mineral Oil, 151, 288 Minority Groups, 48, 288 Mitochondrial Swelling, 288, 290 Mobilization, 181, 288

Modification, 14, 52, 269, 288 Modulator, 14, 51, 288 Molecular Probes, 14, 288 Molecular Structure, 38, 288 Monitor, 11, 46, 61, 152, 163, 217, 247, 256, 288, 293 Monoclonal, 15, 20, 36, 86, 102, 148, 149, 157, 288, 305 Monoclonal antibodies, 20, 36, 86, 148, 149, 157, 288 Monocyte, 26, 288 Mononuclear, 3, 15, 27, 31, 278, 288, 321 Mononucleosis, 138, 219, 288 Morbillivirus, 285, 288 Morphine, 181, 288, 290, 294 Motility, 278, 289, 310 Motor Activity, 289 Motor Endplate, 144, 289 Motor nerve, 289 Motor Neurons, 39, 52, 58, 289 Movement Disorders, 57, 144, 261, 289 Mucins, 289, 308 Mucosa, 263, 269, 284, 289 Mucus, 289, 322 Multiple sclerosis, 40, 180, 289 Multivalent, 47, 48, 147, 176, 183, 184, 242, 289 Muscle Contraction, 156, 179, 289, 291, 292, 308 Muscle relaxant, 163, 170, 289, 292, 315 Muscle Relaxation, 289, 292, 316 Muscle tension, 289 Myalgia, 279, 289 Mycobacterium, 64, 103, 160, 289, 321 Mycological, 162, 289 Mycoplasma, 176, 289 Myelin, 289, 291, 310 Myelitis, 216, 289 Myeloma, 149, 275, 290 Myocarditis, 70, 259, 290 Myocardium, 116, 287, 290 Myosin, 289, 290 Myositis, 68, 290 Myositis Ossificans, 68, 290 N Naive, 15, 16, 21, 25, 29, 62, 78, 290 Narcotic, 288, 290 Nasal Mucosa, 279, 290 Natural killer cells, 31, 290 NCI, 1, 139, 205, 251, 290 Neck Injuries, 256, 290 Necrosis, 7, 270, 278, 287, 290, 307, 310

338 Tetanus

Need, 3, 6, 8, 37, 47, 55, 102, 151, 161, 182, 187, 188, 190, 208, 213, 214, 216, 221, 236, 290, 319 Needle Sharing, 214, 290 Nelfinavir, 10, 290 Neonatal period, 62, 290 Neonatorum, 117, 118, 123, 126, 290 Neoplasm, 159, 160, 290 Neoplastic, 266, 290, 317, 321 Neostriatum, 248, 255, 291, 305 Nerve, 14, 42, 51, 74, 118, 144, 156, 163, 165, 171, 179, 180, 181, 236, 239, 243, 246, 256, 257, 268, 270, 279, 285, 289, 291, 292, 294, 300, 301, 309, 313, 314, 317, 319, 321, 322, 325 Nerve Endings, 291, 317 Nerve Growth Factor, 156, 291 Networks, 14, 23, 55, 291 Neural, 25, 44, 57, 153, 180, 182, 239, 275, 291 Neuroanatomy, 153, 291 Neuroblastoma, 122, 291 Neurodegenerative Diseases, 44, 291 Neuroendocrine, 291, 317 Neuroglia, 270, 291 Neurologic, 28, 39, 40, 147, 270, 291 Neuromuscular, 51, 113, 163, 172, 179, 235, 291, 292 Neuromuscular Blocking Agents, 113, 291 Neuromuscular Depolarizing Agents, 291 Neuromuscular Junction, 51, 179, 235, 291, 292 Neuromuscular Nondepolarizing Agents, 291, 292 Neuronal Plasticity, 42, 292 Neuropeptides, 56, 292 Neurophysiology, 58, 128, 258, 292 Neurosurgery, 57, 68, 75, 292 Neurotoxic, 39, 256, 292, 318 Neurotoxicity, 42, 292 Neurotoxin, 13, 41, 63, 67, 103, 123, 144, 149, 162, 167, 185, 186, 188, 292 Neurotransmitters, 26, 51, 144, 156, 292, 301, 312 Neutralization, 19, 34, 292 Neutrons, 237, 292, 305 Neutrophils, 272, 282, 292 Nevirapine, 10, 292 Nitrogen, 167, 237, 238, 239, 267, 292, 321 Non-nucleoside, 292 Norepinephrine, 236, 251, 260, 293 Nosocomial, 93, 160, 293, 304

Nuclear, 159, 160, 243, 254, 261, 268, 270, 280, 290, 293, 307, 318 Nuclei, 237, 254, 261, 269, 284, 292, 293, 294, 303 Nucleic acid, 159, 160, 182, 184, 185, 269, 275, 276, 292, 293, 304 Nucleic Acid Hybridization, 275, 293 Nucleus, 243, 251, 255, 256, 258, 262, 263, 270, 286, 288, 292, 293, 302, 303, 305, 312 O Observational study, 19, 293 Occult, 217, 293 Occult Blood, 217, 293 Occupational Health, 85, 215, 293 Ocular, 13, 265, 293, 294 Oculi, 245, 293 Odds Ratio, 4, 293 Office Visits, 4, 293 Oligosaccharides, 61, 293 Oliguria, 281, 285, 294 Omega-3 fatty acid, 156, 294 Onchocerciasis, 64, 88, 294 Opacity, 257, 294 Opioid Peptides, 56, 261, 263, 294 Opisthotonos, 170, 230, 294 Opium, 288, 294 Opsin, 294, 307 Optic Nerve, 294, 295, 307 Oral Health, 190, 216, 294 Orbicularis, 245, 294 Orbit, 294 Orbital, 190, 253, 294 Orchiectomy, 142, 294 Organelles, 249, 256, 286, 294 Orgasm, 261, 294 Ornithine, 156, 294 Orofacial, 187, 266, 294 Osmolarity, 285, 294 Osmotic, 237, 288, 294 Ossification, 290, 295 Osteomyelitis, 6, 28, 295 Otitis, 4, 158, 295 Otitis Media, 4, 158, 295 Ovary, 271, 295, 300 Ovum, 257, 270, 282, 295, 301, 325 Oxidation, 150, 235, 241, 245, 256, 260, 283, 295 Oxidative metabolism, 282, 295 Oxidative Stress, 44, 295 Oxygen Consumption, 295, 307 P Pachymeningitis, 286, 295

Index 339

Paclitaxel, 20, 295 Paediatric, 80, 103, 295 Palliative, 295, 318 Palsy, 85, 295 Pancreas, 235, 259, 279, 295, 321 Pancreatic, 130, 295, 297 Papain, 146, 295 Papillomavirus, 7, 296 Par excellence, 19, 296 Paraganglia, Chromaffin, 251, 296 Paralysis, 118, 131, 144, 156, 217, 256, 265, 296, 312 Parasite, 296 Parasitic, 151, 296 Parenteral, 40, 108, 215, 296 Parietal, 70, 296 Parietal Cells, 70, 296 Parietal Lobe, 296 Paroxysmal, 296, 297, 325 Particle, 296, 320 Patch, 12, 32, 43, 54, 60, 114, 296 Pathogen, 15, 19, 40, 60, 159, 160, 278, 296 Pathogenesis, 15, 38, 39, 161, 188, 296 Pathologic, 34, 245, 255, 276, 296, 323 Pathophysiology, 5, 7, 296 Patient Care Team, 8, 296 Patient Education, 7, 213, 224, 226, 233, 296 Pelvic, 3, 296, 302 Pemphigus, 84, 100, 235, 296 Penis, 7, 261, 296 Pepsin, 296, 297 Pepsin A, 297 Peptic, 38, 297 Peptic Ulcer, 38, 297 Peptide T, 156, 297 Perfusion, 54, 297 Pericardium, 297, 317 Perinatal, 118, 278, 297 Perineal, 276, 297 Peripheral blood, 3, 15, 17, 18, 27, 31, 41, 49, 65, 149, 279, 297 Peripheral Nervous System, 171, 291, 295, 297, 301, 315 Pertussis Toxins, 23, 297 Petrolatum, 262, 297 Petroleum, 288, 297 Pharmaceutical Preparations, 265, 269, 298 Pharmacokinetic, 10, 64, 298 Pharmacologic, 9, 40, 239, 242, 272, 298, 320

Pharynx, 279, 298 Phenolphthalein, 262, 298 Phenotype, 41, 49, 59, 298 Phenylalanine, 297, 298, 322 Phospholipases, 298, 311 Phosphorus, 247, 298 Phosphorylation, 12, 117, 298, 303 Photocoagulation, 252, 298 Physical Examination, 10, 298 Physical Fitness, 45, 298 Physiologic, 155, 237, 245, 272, 280, 286, 298, 302, 306 Physiology, 12, 24, 27, 37, 42, 49, 51, 59, 112, 122, 261, 292, 298 Phytotoxin, 298, 308 Pigment, 244, 250, 286, 298 Pilot study, 38, 298 Placenta, 147, 266, 298, 301, 322 Plague, 94, 298, 321 Plant Diseases, 263, 299 Plaque, 41, 250, 299 Plasma cells, 240, 290, 299 Plasma protein, 237, 299 Plasma Volume, 258, 299 Plasmids, 48, 54, 299 Plasmin, 54, 299 Plasminogen, 299 Plasminogen Activators, 299 Plasticity, 14, 34, 42, 53, 299 Platelet Activation, 299, 311 Pneumococcal Vaccines, 90, 299 Poisoning, 126, 189, 247, 269, 280, 286, 299, 310 Pollen, 181, 299 Polyethylene, 169, 179, 300 Polymers, 11, 258, 300, 303 Polymorphic, 258, 287, 300 Polyvalent, 22, 166, 300 Pons, 246, 300 Population Characteristics, 48, 300 Port, 98, 152, 300 Port-a-cath, 300 Positive pressure ventilation, 131, 300 Postnatal, 16, 17, 23, 62, 88, 300, 314 Postoperative, 8, 66, 101, 300 Postsynaptic, 14, 45, 54, 56, 289, 300, 311, 317 Post-synaptic, 50, 300, 317 Post-traumatic, 289, 300 Potassium, 180, 300 Potentiate, 163, 300 Potentiating, 244, 300

340 Tetanus

Potentiation, 14, 23, 284, 300, 311 Practice Guidelines, 209, 301 Precipitation, 143, 301 Preclinical, 29, 66, 301 Precursor, 15, 36, 241, 250, 260, 261, 263, 293, 298, 299, 301, 302, 321, 322 Presynaptic, 23, 45, 51, 53, 56, 59, 179, 289, 291, 301, 316, 317 Presynaptic Terminals, 23, 291, 301, 317 Prevalence, 12, 38, 79, 101, 293, 301 Preventive Medicine, 168, 216, 225, 301 Primary Prevention, 5, 301 Primary tumor, 13, 301 Primary vaccination, 81, 96, 101, 301 Probe, 13, 35, 47, 301 Procaine, 282, 301 Proctocolitis, 30, 301 Progeny, 254, 301 Progesterone, 301, 314 Prognostic factor, 99, 301 Progression, 21, 22, 32, 40, 59, 240, 301, 321 Progressive, 17, 23, 32, 39, 249, 257, 260, 272, 290, 291, 299, 301, 306 Projection, 280, 293, 294, 302, 305 Proline, 165, 174, 252, 275, 302 Promoter, 174, 182, 302 Pro-Opiomelanocortin, 263, 294, 302 Prophase, 245, 289, 302, 317, 318, 322 Prophylaxis, 5, 7, 64, 79, 92, 97, 111, 188, 190, 216, 302, 323 Proportional, 263, 302, 316 Prospective Studies, 17, 30, 302 Prospective study, 97, 302 Prostaglandin, 40, 302, 319 Prostaglandins A, 278, 302 Prostate, 46, 142, 251, 302, 303 Prostate gland, 251, 303 Prostatitis, 3, 303 Prosthesis, 6, 303 Protease, 33, 54, 118, 165, 179, 180, 182, 290, 303, 308 Protease Inhibitors, 33, 303 Protein Binding, 59, 165, 303 Protein Conformation, 238, 303 Protein S, 9, 12, 19, 58, 146, 154, 157, 161, 167, 168, 189, 245, 254, 259, 269, 303, 308 Protein Subunits, 19, 303 Protein-Tyrosine Kinase, 269, 303 Proteolytic, 38, 54, 103, 129, 158, 180, 181, 182, 253, 263, 295, 299, 303, 308 Protocol, 25, 61, 137, 303

Proton Pump, 35, 303 Protons, 35, 237, 275, 303, 305 Proto-Oncogene Proteins, 295, 303 Proto-Oncogene Proteins c-mos, 295, 303 Protozoa, 254, 287, 304, 313 Proximal, 260, 301, 304 Pruritic, 261, 304, 319 Pruritus, 294, 304 Pseudomonas, 55, 160, 304 Pseudomonas aeruginosa, 160, 304 Psychiatry, 10, 68, 75, 267, 304, 323 Psychic, 282, 304, 310 Psychogenic, 98, 304 Psychology, 55, 118, 260, 304 Public Health, 4, 20, 28, 45, 86, 107, 110, 117, 123, 127, 180, 189, 209, 216, 304 Public Policy, 207, 304 Publishing, 5, 63, 187, 218, 304 Pulmonary, 60, 89, 245, 254, 263, 281, 282, 304, 316, 323 Pulmonary Artery, 245, 304, 323 Pulse, 29, 53, 152, 288, 304 Purifying, 167, 258, 304 Purines, 304, 310 Pustular, 277, 304 Putamen, 255, 291, 305 Putrefaction, 268, 305 Pyogenic, 295, 305, 310 Pyramidal Cells, 23, 258, 305 Pyridoxal, 305, 320 Pyrogenic, 160, 305 Q Quaternary, 129, 303, 305, 315 Quiescent, 34, 178, 305 R Rabies, 5, 7, 160, 305 Race, 287, 305 Radiation, 6, 235, 262, 265, 267, 268, 276, 277, 305, 309, 314, 321, 325 Radiation therapy, 235, 265, 268, 276, 305, 321 Radioactive, 154, 246, 272, 275, 283, 288, 293, 305, 309 Radiography, 181, 190, 255, 305 Radioisotope, 305, 320 Radiolabeled, 38, 305 Radiopharmaceutical, 269, 305 Randomized, 10, 16, 28, 40, 43, 45, 62, 69, 87, 108, 137, 261, 305 Reabsorption, 35, 305 Reactivation, 16, 306 Reagent, 171, 259, 275, 306

Index 341

Receptor, 19, 20, 24, 25, 26, 27, 32, 33, 47, 49, 51, 52, 53, 54, 56, 58, 59, 119, 131, 143, 162, 180, 181, 184, 185, 235, 240, 260, 271, 287, 297, 306, 310, 311 Receptors, Serotonin, 306, 310 Recombinant Proteins, 158, 306 Recombination, 254, 306 Reconstitution, 15, 16, 19, 37, 306 Rectal, 57, 306 Rectum, 241, 246, 252, 259, 268, 278, 282, 301, 303, 306, 316 Red blood cells, 264, 273, 306, 308 Refer, 1, 246, 253, 263, 267, 268, 274, 280, 283, 288, 290, 292, 293, 306 Reflex, 30, 57, 306 Refraction, 306, 313 Regeneration, 51, 306 Regimen, 10, 261, 306 Relapse, 46, 61, 138, 306 Relaxant, 163, 306, 315 Renal failure, 28, 108, 306 Renin, 247, 306 Renin-Angiotensin System, 247, 306 Reperfusion, 168, 306, 307 Reperfusion Injury, 307 Research Design, 45, 307 Research Support, 52, 307 Residual disease, 29, 307 Respiration, 152, 241, 247, 256, 288, 295, 307 Respirator, 300, 307 Respiratory distress syndrome, 190, 307 Respiratory failure, 89, 104, 307 Respiratory Physiology, 114, 307, 323 Restoration, 16, 57, 306, 307, 325 Retina, 46, 251, 254, 282, 291, 294, 307, 308, 324 Retinal, 46, 294, 307 Retinal Ganglion Cells, 46, 294, 307 Retinoid, 52, 307 Retinol, 62, 307 Retinyl palmitate, 62, 308 Retrograde, 39, 59, 154, 171, 181, 308 Retrospective, 69, 89, 98, 104, 308 Retrospective study, 69, 308 Reversion, 308, 321 Rheumatism, 308 Rheumatoid, 53, 58, 142, 143, 308 Rheumatoid arthritis, 53, 58, 142, 143, 308 Rhinitis, 181, 246, 287, 308, 310 Ribose, 236, 308 Ribosome, 308, 320

Ricin, 47, 167, 308 Risk factor, 5, 17, 28, 89, 93, 98, 99, 104, 116, 121, 125, 217, 302, 308 Ritonavir, 10, 308 Rod, 243, 251, 272, 304, 308 Rotavirus, 78, 308 Rubella, 5, 84, 132, 176, 214, 215, 216, 217, 218, 219, 285 S Saline, 62, 166, 173, 308 Saliva, 17, 108, 308 Salivary, 57, 107, 256, 259, 308, 315 Salivary glands, 256, 259, 308 Saponins, 308, 314 Sarcoplasmic Reticulum, 122, 308 Saturate, 32, 308 Scans, 41, 309 Schizoid, 309, 325 Schizophrenia, 309, 325 Schizotypal Personality Disorder, 309, 325 Sclerosis, 40, 168, 289, 309 Screening, 48, 216, 251, 309, 322 Scrotum, 309, 318, 323 Second Messenger Systems, 292, 309 Secondary tumor, 287, 309 Secretory, 35, 162, 251, 309, 317 Secretory Vesicles, 251, 309 Sedative, 25, 309 Sedentary, 45, 309 Sediment, 309, 322 Segmental, 180, 309 Segmentation, 309 Seizures, 17, 23, 32, 104, 231, 270, 296, 309 Semen, 261, 302, 303, 310 Seminal vesicles, 310, 323 Seminiferous tubule, 310, 313 Senescence, 15, 53, 310 Sensitization, 87, 310 Sensor, 47, 310 Sensory loss, 289, 310 Sepsis, 28, 147, 161, 310 Septicaemia, 310 Septicemia, 158, 161, 310 Sequence Homology, 297, 310 Sequencing, 63, 310 Sequester, 310, 317 Serine, 34, 54, 263, 304, 310, 321 Seroconversion, 164, 310 Serologic, 107, 277, 310 Serotonin, 117, 118, 129, 130, 244, 306, 310, 321 Serotypes, 66, 144, 158, 165, 179, 310

342 Tetanus

Sex Characteristics, 239, 265, 311, 318 Sexually Transmitted Diseases, 50, 311 Shock, 181, 232, 239, 262, 267, 311, 321 Side effect, 8, 9, 170, 176, 179, 199, 236, 244, 311, 320 Sigmoid, 311 Sigmoidoscopy, 48, 217, 311 Signal Transduction, 42, 116, 248, 279, 311 Signs and Symptoms, 306, 311 Skeletal, 122, 155, 201, 239, 251, 256, 291, 292, 308, 311, 312, 315 Skeleton, 235, 281, 302, 311 Skin Tests, 31, 311 Skull, 256, 294, 296, 311, 318 Sleep apnea, 155, 311 Small intestine, 263, 274, 280, 311, 321 Smooth muscle, 237, 239, 242, 247, 274, 288, 306, 311, 312, 315 Sneezing, 297, 312 Social Support, 55, 312 Socioeconomic Factors, 300, 312 Sodium, 181, 305, 312 Soft tissue, 28, 245, 290, 311, 312 Solid tumor, 260, 312 Solitary Nucleus, 242, 312 Solvent, 265, 294, 312 Soma, 142, 201, 305, 312 Somatic, 20, 148, 149, 256, 270, 275, 286, 297, 312 Sorbitol, 285, 312 Spasm, 144, 180, 245, 255, 294, 312 Spasmodic, 144, 297, 312, 321 Spastic, 180, 312 Spasticity, 57, 180, 231, 243, 312 Specialist, 119, 221, 312 Specificity, 42, 47, 57, 143, 144, 237, 247, 263, 313 Spectrum, 28, 30, 179, 313 Sperm, 24, 34, 239, 251, 299, 310, 313, 318 Sperm Maturation, 34, 313 Sperm Motility, 34, 313 Spermatogenesis, 142, 313 Spermatozoa, 49, 310, 313, 323 Spermatozoon, 313 Sphenoid, 296, 313 Spinal Cord Vascular Diseases, 289, 313 Spinal Nerves, 297, 313 Spirochete, 313, 317 Spleen, 256, 275, 284, 313 Sporadic, 291, 313 Spores, 170, 232, 313 Sporotrichosis, 7, 313

Squamous, 111, 264, 313, 314 Squamous cell carcinoma, 111, 264, 313, 314 Squamous cells, 313, 314 Stabilizer, 247, 314 Staging, 309, 314 Staphylococcus, 19, 269, 277, 314 Staphylococcus aureus, 19, 269, 277, 314 Steel, 251, 314 Stem cell transplantation, 29, 61, 314 Stem Cells, 314 Stereotactic, 58, 314 Stereotaxis, 57, 314 Sterile, 126, 314, 321 Sterility, 278, 314 Sterilization, 219, 314 Steroid, 24, 255, 308, 314 Stimulant, 239, 247, 274, 314 Stimulus, 50, 51, 181, 260, 261, 265, 277, 279, 280, 306, 314, 318 Stomach, 235, 244, 259, 263, 265, 268, 269, 274, 296, 298, 311, 313, 315 Strabismus, 180, 315 Streptococcal, 7, 56, 90, 93, 315 Streptococcal Infections, 56, 315 Streptococci, 147, 162, 277, 315 Streptococcus, 28, 65, 90, 107, 113, 147, 184, 264, 299, 315 Stress, 11, 55, 168, 242, 248, 251, 255, 262, 269, 295, 308, 315, 323 Striatum, 53, 291, 315 Stroke, 11, 14, 39, 140, 168, 180, 206, 248, 315 Stroke Volume, 11, 248, 315 Stromal, 49, 315 Subacute, 278, 315 Subclinical, 278, 309, 315 Subcutaneous, 137, 215, 261, 268, 290, 294, 296, 313, 315 Subiculum, 274, 315 Submaxillary, 264, 315 Subspecies, 312, 315 Substance P, 149, 287, 306, 309, 315 Substrate, 13, 14, 33, 45, 47, 123, 171, 174, 179, 263, 315, 322 Succinylcholine, 129, 163, 315 Suction, 266, 316 Sufentanil, 97, 316 Superoxide, 168, 316 Superoxide Dismutase, 168, 316 Supplementation, 62, 71, 119, 122, 123, 126, 131, 316

Index 343

Suppositories, 269, 316 Suppression, 16, 49, 142, 179, 316 Suppressive, 31, 316 Supraspinal, 243, 316 Surface Plasmon Resonance, 47, 316 Surfactant, 9, 316 Suspensions, 166, 243, 316 Sympathetic Nervous System, 122, 242, 251, 292, 316 Sympathomimetic, 239, 260, 264, 293, 316, 322 Symphysis, 303, 316 Symptomatic, 55, 208, 316 Synapses, 14, 23, 32, 44, 51, 56, 154, 156, 246, 284, 292, 316, 317 Synapsis, 317 Synaptic, 14, 32, 34, 39, 42, 50, 51, 52, 53, 56, 57, 67, 153, 182, 184, 185, 283, 289, 311, 317 Synaptic Transmission, 14, 317 Synaptic Vesicles, 51, 317 Synaptophysin, 50, 317 Synaptosomes, 116, 117, 317 Synergistic, 9, 52, 317 Syphilis, 219, 317 Systemic lupus erythematosus, 143, 218, 317 T Tachycardia, 231, 243, 317 Tachypnea, 243, 317 Teichoic Acids, 272, 317 Telencephalon, 243, 317 Temporal, 274, 296, 318 Terminator, 146, 318 Testicles, 294, 309, 318 Testosterone, 142, 318 Tetani, 41, 43, 48, 67, 77, 113, 146, 149, 156, 162, 167, 182, 183, 184, 318 Tetanic, 155, 318 Tetravalent, 78, 318 Thalamus, 255, 318 Therapeutics, 82, 92, 116, 124, 180, 201, 318 Thermal, 161, 260, 292, 318 Thioguanine, 148, 318 Thoracic, 246, 318, 322, 325 Thorax, 235, 318 Threonine, 34, 297, 304, 310, 318 Threshold, 56, 155, 318 Thrombin, 266, 303, 318, 319 Thrombocytopenia, 143, 318 Thrombomodulin, 303, 319

Thrombosis, 7, 303, 315, 319 Thromboxanes, 241, 319 Thylakoids, 250, 319 Thymus, 16, 150, 276, 284, 319 Thyroid, 217, 280, 319, 322 Thyroxine, 237, 298, 319 Tinea Pedis, 7, 319 Tinnitus, 295, 319 Tissue, 7, 16, 44, 49, 55, 154, 155, 156, 157, 165, 180, 181, 235, 240, 242, 243, 244, 245, 246, 247, 250, 252, 254, 256, 260, 261, 262, 263, 266, 268, 269, 270, 271, 272, 276, 278, 280, 282, 284, 285, 286, 287, 289, 290, 291, 292, 295, 296, 297, 298, 299, 306, 307, 310, 311, 312, 313, 314, 316, 317, 319, 321, 325 Titre, 80, 319 Tolerance, 30, 40, 93, 157, 235, 271, 319 Tonic, 245, 283, 319 Tonicity, 261, 319 Tonsillitis, 4, 319 Tonsils, 319 Tooth Preparation, 236, 319 Topical, 43, 76, 98, 117, 200, 241, 250, 265, 275, 295, 297, 319 Torticollis, 144, 180, 320 Toxicity, 18, 20, 22, 42, 44, 46, 61, 62, 184, 185, 260, 286, 320 Toxicokinetics, 320 Toxicology, 89, 117, 179, 208, 320 Trace element, 251, 320 Tracer, 153, 274, 320 Trachea, 246, 282, 298, 319, 320 Traction, 251, 320 Transaminase, 39, 44, 320 Transcriptase, 292, 320 Transcription Factors, 320, 324 Transcutaneous, 60, 320 Transduction, 43, 47, 52, 311, 320 Transfection, 17, 245, 320 Transfer Factor, 276, 320 Transferases, 271, 320 Translation, 159, 160, 320 Translocating, 185, 186, 321 Translocation, 162, 167, 185, 186, 321 Transmitter, 51, 56, 235, 242, 260, 280, 285, 291, 293, 316, 317, 321, 322 Transplantation, 7, 9, 16, 19, 69, 81, 93, 149, 276, 284, 321 Trauma, 7, 26, 71, 109, 168, 187, 190, 256, 290, 321, 325 Trigeminal, 266, 321

344 Tetanus

Trismus, 6, 321 Trivalent, 146, 321 Trophic, 59, 321 Tropism, 31, 57, 321 Trypsin, 42, 263, 321 Tryptophan, 252, 310, 321 Tubercle, 151, 321 Tuberculin, 31, 74, 321 Tuberculosis, 116, 160, 208, 216, 218, 219, 254, 284, 321 Tularemia, 60, 321 Tumor model, 36, 321 Tumor Necrosis Factor, 52, 321 TYPHI, 40, 47, 48, 57, 64, 104, 164, 321 Typhimurium, 174, 321 Typhoid fever, 164, 321 Tyramine, 244, 322 Tyrosine, 21, 34, 42, 54, 112, 123, 260, 303, 322 U Ulcer, 38, 297, 322 Ulcerative colitis, 5, 278, 322 Ulnar Nerve, 163, 322 Umbilical Arteries, 322 Umbilical Cord, 43, 125, 250, 322 Unconscious, 240, 276, 322 Univalent, 275, 295, 322 Universal Precautions, 218, 322 Urea, 145, 294, 322 Uremia, 281, 306, 322 Ureters, 322 Urethra, 296, 302, 303, 322, 323 Urinalysis, 216, 322 Urinary, 28, 218, 243, 278, 294, 304, 322, 323 Urinary tract, 28, 218, 243, 304, 322 Urinary tract infection, 28, 218, 243, 304, 322 Urine, 17, 243, 245, 256, 258, 260, 264, 278, 294, 322, 323 Urogenital, 271, 323 Urticaria, 6, 30, 143, 181, 239, 323 Uterus, 250, 255, 257, 262, 286, 301, 323 V Vaccine adjuvant, 61, 323 Vacuoles, 262, 294, 323 Vagina, 250, 258, 286, 323, 325 Vaginal, 200, 323, 325 Varicella, 214, 215, 216, 217, 219, 323 Vas Deferens, 34, 323 Vascular, 74, 237, 239, 251, 258, 278, 298, 299, 313, 323

Vasculitis, 7, 323 Vasoactive, 181, 323 Vasoconstriction, 264, 323 Vasodilator, 260, 274, 323 Vector, 27, 39, 43, 48, 52, 57, 104, 145, 159, 160, 168, 182, 320, 323 Vein, 280, 293, 322, 323 Venereal, 317, 323 Venom, 256, 323 Venous, 7, 303, 323 Ventilation, 5, 323 Ventricle, 248, 274, 276, 304, 318, 323, 324 Ventricular, 11, 12, 116, 324 Vertebrae, 313, 324 Vertebral, 6, 324 Vertigo, 295, 324 Vesicular, 144, 274, 324 Veterinary Medicine, 116, 123, 207, 324 Vibrio, 55, 63, 66, 174, 175, 177, 178, 250, 324 Vibrio cholerae, 63, 66, 174, 177, 178, 250, 324 Viral, 7, 9, 15, 17, 20, 24, 29, 47, 57, 151, 153, 212, 213, 262, 279, 305, 320, 324, 325 Viral Load, 9, 15, 17, 324 Viral vector, 57, 324 Virulence, 38, 158, 242, 244, 320, 324 Virus Latency, 52, 324 Viscera, 312, 324 Visceral, 142, 242, 256, 270, 324 Visceral Afferents, 242, 270, 324 Vitreous Body, 307, 324 Vitro, 9, 11, 22, 23, 26, 27, 32, 34, 35, 39, 41, 52, 53, 59, 88, 117, 148, 149, 161, 165, 184, 185, 244, 273, 278, 324 Vivo, 10, 11, 20, 22, 26, 29, 33, 34, 37, 39, 41, 46, 52, 58, 59, 149, 161, 165, 181, 184, 185, 244, 273, 278, 319, 324 Volition, 280, 324 Voluntary Health Agencies, 276, 324 Vulva, 7, 325 W Warts, 7, 325 Wheezing, 287, 325 White blood cell, 240, 263, 278, 282, 284, 288, 289, 290, 299, 325 Whooping Cough, 175, 184, 212, 217, 259, 297, 325 Windpipe, 298, 319, 325 Withdrawal, 46, 325 World Health, 82, 98, 99, 112, 121, 154, 166, 189, 208, 233, 325

Index 345

Wound Healing, 7, 325 Wound Infection, 6, 190, 325 X Xenograft, 240, 321, 325 X-ray, 33, 248, 253, 254, 267, 285, 293, 305, 309, 314, 325

Y Yeasts, 268, 298, 325 Z Zoonoses, 305, 325 Zoster, 215, 325 Zygote, 254, 325 Zymogen, 130, 303, 325

346 Tetanus

Index 347

348 Tetanus

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