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

COLCHICINE A 3-IN-1 MEDICAL REFERENCE Medical Dictionary Bibliography & Annotated Research Guide TO I NTERNET

R EFERENCES

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

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

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ICON Health Publications ICON Group International, Inc. 4370 La Jolla Village Drive, 4th Floor San Diego, CA 92122 USA Copyright 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., 1960Colchicine: 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: 0-497-00278-7 1. Colchicine-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 colchicine. 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 COLCHICINE ............................................................................................. 3 Overview........................................................................................................................................ 3 The Combined Health Information Database................................................................................. 3 Federally Funded Research on Colchicine...................................................................................... 6 E-Journals: PubMed Central ....................................................................................................... 25 The National Library of Medicine: PubMed ................................................................................ 28 CHAPTER 2. NUTRITION AND COLCHICINE.................................................................................... 71 Overview...................................................................................................................................... 71 Finding Nutrition Studies on Colchicine..................................................................................... 71 Federal Resources on Nutrition ................................................................................................... 73 Additional Web Resources ........................................................................................................... 73 CHAPTER 3. ALTERNATIVE MEDICINE AND COLCHICINE ............................................................. 75 Overview...................................................................................................................................... 75 National Center for Complementary and Alternative Medicine.................................................. 75 Additional Web Resources ........................................................................................................... 81 General References ....................................................................................................................... 83 CHAPTER 4. DISSERTATIONS ON COLCHICINE ............................................................................... 85 Overview...................................................................................................................................... 85 Dissertations on Colchicine ......................................................................................................... 85 Keeping Current .......................................................................................................................... 86 CHAPTER 5. PATENTS ON COLCHICINE .......................................................................................... 87 Overview...................................................................................................................................... 87 Patents on Colchicine................................................................................................................... 87 Patent Applications on Colchicine ............................................................................................... 99 Keeping Current ........................................................................................................................ 100 CHAPTER 6. BOOKS ON COLCHICINE ............................................................................................ 101 Overview.................................................................................................................................... 101 Book Summaries: Federal Agencies............................................................................................ 101 The National Library of Medicine Book Index ........................................................................... 102 Chapters on Colchicine............................................................................................................... 102 CHAPTER 7. PERIODICALS AND NEWS ON COLCHICINE .............................................................. 105 Overview.................................................................................................................................... 105 News Services and Press Releases.............................................................................................. 105 Academic Periodicals covering Colchicine ................................................................................. 107 CHAPTER 8. RESEARCHING MEDICATIONS .................................................................................. 109 Overview.................................................................................................................................... 109 U.S. Pharmacopeia..................................................................................................................... 109 Commercial Databases ............................................................................................................... 110 APPENDIX A. PHYSICIAN RESOURCES .......................................................................................... 113 Overview.................................................................................................................................... 113 NIH Guidelines.......................................................................................................................... 113 NIH Databases........................................................................................................................... 115 Other Commercial Databases..................................................................................................... 117 APPENDIX B. PATIENT RESOURCES ............................................................................................... 119 Overview.................................................................................................................................... 119 Patient Guideline Sources.......................................................................................................... 119 Finding Associations.................................................................................................................. 121 APPENDIX C. FINDING MEDICAL LIBRARIES ................................................................................ 123 Overview.................................................................................................................................... 123 Preparation................................................................................................................................. 123

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Finding a Local Medical Library................................................................................................ 123 Medical Libraries in the U.S. and Canada ................................................................................. 123 ONLINE GLOSSARIES................................................................................................................ 129 Online Dictionary Directories ................................................................................................... 129 COLCHICINE DICTIONARY..................................................................................................... 131 INDEX .............................................................................................................................................. 197

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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 colchicine 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 colchicine, 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 colchicine, 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 colchicine. 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 colchicine, 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 colchicine. The Editors

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

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

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

Diagnosis and Management of Gout Source: American Family Physician. 59(7): 1799-1806. April 1, 1999. Contact: Available from American Academy of Family Physicians. 11400 Tomahawk Creek Parkway, Leawood, KS 66211-2672. (800) 274-2237. Website: www.aafp.org. Summary: Gout is a disease resulting from the deposition of urate crystals caused by the overproduction or underexcretion of uric acid. The disease is often, but not always, associated with elevated serum uric acid levels. This article reviews the diagnosis and management of gout. Clinical manifestations include acute and chronic arthritis, tophi (nodular masses of monosodium urate crystals deposited in the soft tissues of the body), interstitial renal disease, and uric acid nephrolithiasis (kidney stones). The diagnosis is based on the identification of uric acid crystals in joints, tissues, or body fluids. Because

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patients with gout typically have hypertension and impaired renal function, examination of the renal and cardiovascular systems is essential. Treatment goals include termination of the acute attack, prevention of recurrent attacks, and prevention of complications associated with the deposition of urate crystals in tissues. Pharmacologic management remains the mainstay of treatment. Acute attacks may be terminated with the use of nonsteroidal antiinflammatory agents (NSAIDs), colchicine, or intra articular injections of corticosteroids. Probenicid, sulfinpyrazone, and allopurinol can be used to prevent recurrent attacks. The authors note that obesity, alcohol intake, and certain foods and medications can contribute to hyperuricemia. These potentially exacerbating factors should be identified and modified. A patient information handout on gout, written by the authors of this article, is provided on a separate page in this same journal issue. 6 figures. 2 tables. 24 references. •

Renal Amyloidosis in a Drug Abuser Source: Journal of the American Society of Nephrology. 5(9): 1653-1658. March 1995. Contact: Available from Williams and Wilkins. 428 East Preston Street, Baltimore, MD 21202-3993. (800) 638-6423. Summary: In this article, the authors present the case of a patient who had a history of subcutaneous cocaine and heroin use and who developed nephrotic syndrome, with an elevated serum creatinine and a creatinine clearance of 61 mL/min. Renal biopsy demonstrated amyloidosis. Treatment with colchicine was initiated, and proteinuria decreased to near normal levels after 12 months. Concomitant with the decrease in proteinuria, creatinine clearance improved, although a repeat renal biopsy failed to show any significant improvement in amyloid burden. The authors suggest that colchicine may be a useful treatment in reversing the proteinuria of renal amyloidosis associated with drug abuse. Furthermore, clinical improvement may occur before any demonstrable regression in the amyloidosis. 1 figure. 3 tables. 25 references.

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Alcoholic Liver Disease: Latest Guidelines for Detecting and Managing Source: Consultant. 39(3): 799-800, 805-807. March 1999. Contact: Available from Cliggott Publishing Company. 55 Holly Hill Lane, Box 4010, Greenwich, CT 06831-0010. Summary: More than 11,000 Americans die each year of alcoholic cirrhosis of the liver. This article briefly summarizes the latest guidelines from the American College of Gastroenterology for detecting and managing alcoholic liver disease (ALD). The article notes that the problem of ALD is aggravated both by an imperfect knowledge of its pathogenesis and natural course and by the frequent failure to identify patients who are at risk or have subclinical disease. Susceptibility to the different forms of ALD also varies greatly among heavy drinkers, as does the severity of the disease. The article reviews the CAGE questionnaire, a screening tool used for alcohol abuse and dependency. Among the physical findings that may accompany ALD are those related to portal hypertension (ascites, splenomegaly, abdominal wall collaterals, and venous hum), hepatic injury (cutaneous telangiectasia, palmar erythema, finger clubbing, Dupuytrens contracture, and peripheral neuropathy), and, in men, feminization. Laboratory findings are reviewed, and the article notes that liver biopsy may be warranted to confirm the diagnosis of ALD, to exclude other causes of liver disease, or to assess the extent of liver damage, refine the prognosis, and guide therapeutic decisions. The amount of alcohol consumed is the most important risk factor for the development of ALD. The article reviews the management of patients with ALD,

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including nutritional therapy, propylthiouracil, colchicine, and liver transplantation. 1 figure. 3 tables. 13 references. •

Alcoholic Liver Disease: The ACG's Recommendations Source: Journal of Critical Illness. 14(5): 264-268. May 1999. Contact: Available from Cliggott Publishing Company. 55 Holly Hill Lane, Greenwich, CT 06831-0010. (203) 661-0600. Summary: The problem of alcoholic liver disease (ALD) is aggravated both by the imperfect knowledge of its pathogenesis and natural course and by the frequent failure to identify patients who are at risk or have subclinical disease. Guidelines for the management of ALD were developed for the Practice Parameters Committee of the American College of Gastroenterology and published recently in the American Journal of Gastroenterology. This article provides a brief summary of these recommendations, which address detection and diagnosis, risk factors and prognosis, nutritional therapy, the use of propylthiouracil (PTU), the use of colchicine, liver transplantation, and treating alcoholic hepatitis. The author includes the CAGE questionnaire as a screening tool for alcohol abuse and dependency. Laboratory findings characteristic of ALD include elevated levels of aspartate aminotransferase and of alinine aminotransferase. Liver biopsy may be warranted to confirm the diagnosis of ALD; to exclude other causes of liver disease; or to assess the extent of liver damage, refine the prognosis, and guide therapeutic decisions. The amount of alcohol consumed is the most important risk factor for the development of ALD. A number of studies have shown that it is worthwhile to use aggressive nutritional therapy in ALD to prevent protein calorie malnutrition. Generally, patients with mild alcoholic hepatitis need only supportive and symptomatic care, while the most severely ill patients may fail to respond to any treatment. Aggressive therapy is most likely to benefit those between these two extremes. 1 figure. 3 tables. 14 references.

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Alcoholic Liver Disease: Treatment Strategies for the Potentially Reversible Stages Source: Postgraduate Medicine. 103(4): 261-264, 267-268, 273-275. January 1998. Contact: Available from McGraw-Hill, Inc. 1221 Avenue of the Americas, New York, NY 10020. (612) 832-7869. Summary: This article reviews treatment strategies for the potentially reversible stages of alcoholic liver disease. The authors note that although liver damage resulting from heavy drinking may be subclinical for a long period, steatosis may begin after even minor bouts of overconsumption. If alcohol consumption continues, alcoholic liver disease often is fatal. The authors discuss classification, clinical presentation, laboratory findings, nutritional considerations, treatment strategies, nutritional support, the pathogenesis of alcoholic liver disease, steroid therapy, other drug therapies, and liver transplantation. Most patients with clinically significant alcoholic liver disease have histologic findings typical of steatosis, alcoholic hepatitis, and cirrhosis. Abstinence from alcohol, in combination with proper nutrition and general supportive care, is required. Steatosis is reversible upon withdrawal of alcohol, but alcoholic hepatitis can persist even with abstinence and may progress to cirrhosis. Corticosteroid therapy may reduce short term mortality rates in patients with moderate or severe alcoholic hepatitis who have hepatic encephalopathy but no evidence of infection or gastrointestinal bleeding. Treatment with colchicine may decrease the risk of cirrhosis; however, once cirrhosis has developed, the liver damage is irreversible. Liver transplantation may be considered in patients with severe complications. 4 figures. 1 table. 31 references.

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Primary Biliary Cirrhosis Source: New England Journal of Medicine. 335(21): 1570-1580. November 21, 1996. Summary: This review article covers primary biliary cirrhosis, a chronic, progressive cholestatic liver disease of unknown cause that usually affects middle-aged women and eventually leads to liver failure and the need for liver transplantation. The author reports on the recent advances in the natural history, pathogenesis, and treatment of primary biliary cirrhosis in detail; in addition, the pathological features, diagnosis, and clinical manifestations are briefly covered. The author describes various drug regimens used to treat primary biliary cirrhosis, noting that there is no generally accepted treatment for the underlying disease process, but the results with ursodiol, colchicine, and methotrexate are encouraging. Glucocortoids do not appear to improve the course of the disease and may worsen osteoporosis. Azathioprine has limited efficacy and is no longer used. Penicillamine, an agent that induces cupriuria and has some antiinflammatory actions, is ineffective and presents troublesome side effects. The most common symptom that is relatively specific for primary biliary cirrhosis is pruritis (itching). Cholestyramine resin (4 g three times per day orally) will relieve pruritus in most patients. 1 figure. 153 references.

Federally Funded Research on Colchicine The U.S. Government supports a variety of research studies relating to colchicine. 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 colchicine. 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 colchicine. The following is typical of the type of information found when searching the CRISP database for colchicine: •

Project Title: ANGIOGENESIS FOLLOWING STROKE Principal Investigator & Institution: Lyden, Patrick D.; Professor; Veterans Medical Research Fdn/San Diego Foundation of San Diego San Diego, Ca 92161 Timing: Fiscal Year 2003; Project Start 15-DEC-2002; Project End 30-NOV-2006 Summary: (provided by applicant): Although peptide angiogenic signals may promote new vessel formation, may offer neuroprotection, and may facilitate neuronal migration during recovery, our pilot data suggests a different function after ischemia: the brain may utilize angiogenic signaling only to subserve removal of necrotic debris, i.e., "cleanup". Our central hypothesis is that after ischemia, angiogenic growth factors are secreted

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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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to open blood brain barrier, stimulate macrophage infiltration, and to create vascular channels for removal of necrotic debris. Our aims are: we will measure capillary and neuronal density 30 days after focal brain ischemia to establish whether ischemia stimulates persisting microvessels, preserves neurons, or both. Then we will determine if microvessel or neuronal densities can be augmented with intra-arterial infusions of VEGF or bFGF or both. Do Macrophages Influence the Growth of New Microvessls? We will block macrophage entry into the brain by depleting them (whole body irradiation) or inhibiting them (colchicine/chloroquine), and expect to see a marked reduction of both macrophages and microvessels near the ischemic zone. We will increase macrophage entry into the ischemic zone with tissue necrosis factor, macrophage inflammatory protein-I, or monocyte chemoattractant protein-1 and expect to find more microvessels and macrophages. We will inhibit VEGF activity immediately after ischemia with anti-VEGFR antibody, a VEGFR-Fc fusion protein, and a tyrosine kinase inhibitor specific for VEGFR. Does Angiopoietin-2 Signal Microvessel Degradation? We will provide VEGF beginning 10 days after stroke and continuing to 17 days after stroke, to blunt the degradation signal; we predict that microvessels will persist. We will administer a TIE-2 receptor-Fc binding protein from Day 10 to 17 after stroke to bind and remove TIE-2 ligands (especially Ang-2), again predicting that microvessels will persist. Does angiogenic signaling ameliorate cognitive deficit after stroke? Using a bioassay suited to studying pharmacological synergism, we will study protective effects of VEGF, bFGF, or both using a bioassay and a spatial navigation test. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •

Project Title: ASTHMA CLINICAL RESEARCH NETWORK Principal Investigator & Institution: Israel, Elliot; Brigham and Women's Hospital 75 Francis Street Boston, Ma 02115 Timing: Fiscal Year 2002; Project Start 30-SEP-1993; Project End 31-AUG-2004 Summary: This application is for the continuation of the Asthma Clinical Research Network or ACRN. The ACRN is an interactive network of 6 research centers conducting studies of novel therapeutic approaches to asthma. The need for such a network was suggested by epidemiological data showing increases in the mortality, morbidity, prevalence, and costs of asthma, by clinical and basic research studies showing that asthma is linked to inflammation in the airways, and by the accelerating rate of development of potentially highly effective, but also potentially costly novel treatments for asthma. Defining the place of these new therapies was seen as requiring collaborative, multi-center studies examining large numbers of subjects reflecting the diversity of the U.S. population. In its first 5 years, the ACRN established an interactive infrastructure to meet this need and has added a clinical research site at Harlem Hospital in New York, which serves a predominantly minority population. The ACRN completed and published trials of the effects of regular use of a beta-agonist in subjects with mild asthma ( BAGS ) and of the efficacy of the anti-inflammatory agent, colchicine, as an alternate to an inhaled corticosteriod in moderate asthma. It is now conducting two additional trials comparing the effects of a long-acting beta-agonist, an inhaled corticosteriod, and the combination of the two in altering clinical outcomes, physiologic outcomes, and airway inflammation in moderate or severe asthma. A fifth study, establishing doses of different inhaled corticosteriods with equivalent effects on cortisol secretion, is about to be started. Data from completed trials, and associated ancillary studies, has been presented at national meeting to the ATS, ACCP, and AAAAI. This application specifically outlines the goals of the ACRN over the next five years. The studies proposed include: 1) A comparison of the clinical efficacy of doses of

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different inhaled corticosteriods with equal systemic effects (as estimated from the study described above), 2) A prospective study of the effects of regular use of an inhaled betaagonist in subjects stratified by genotype for the beta-adrenergic receptor, 3) A study analyzing the efficacy of a leukotriene pathway antagonist in enabling reduction or elimination of inhaled corticosteriod therapy in subjects with mild or moderate persistent asthma; and 4) six other studies from which 3 will be chosen for execution during the next five years. Other studies will be considered if new information becomes available suggesting the need for additional trials. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •

Project Title: ASTHMA CLINICAL RESEARCH NETWORK Principal Investigator & Institution: Dimango, Emily A.; Medicine; Columbia University Health Sciences Po Box 49 New York, Ny 10032 Timing: Fiscal Year 2002; Project Start 08-DEC-1995; Project End 31-AUG-2004 Summary: This application proposes to continue the participation of investigators at the New York City Center in an interactive network of six centers, the Asthma Clinical Research Network (ACRN) in conducting studies of novel therapies for asthma and in disseminating findings to the practicing community. The need for such a network was suggested by increases in the mortality, morbidity, prevalence, and costs of asthma, by research studies showing that asthma is linked to airway inflammation, and by the accelerating rate of development of potentially effective, but also potentially costly treatments. Defining the place of these new therapies was seen as requiring collaborative, multi-center studies examining subjects reflecting the diversity of the U.S. population. In its first 5 years, the ACRN established an interactive infrastructure and added a research site at Harlem Hospital, New York, which serves a predominantly minority population. The ACRN completed and published trials of the effects of regular use of a beta-agonist in mild asthma ( BAGS ) and of the efficacy of colchicine as an alternate to an inhaled corticosteroid (ICS) in moderate asthma. It is now conducting trials comparing a long-acting beta-agonist, an ICS, and the combination of the two in moderate to severe asthma. We are about to start a 5th study to establish doses of different ICS with equivalent effects on cortisol secretion. These studies have been presented at meetings of the ATS, ACCP, and AAAAI, as have 10-12 ancillary studies analyzing the performance of clinical research. The ACRN has also reported its findings from subgroup analysis of the BAGS study: that subjects with different genotypes for the beta-adrenergic receptor are differently affected by regular use of albuterol. This application proposes continued participation of the NYC Asthma Clinical Research group in the multicentered, collaborative trials of the ACRN. The studies proposed include a comparison of the clinical efficacy of doses of different inhaled corticosteriods with equal systemic effects, a prospective study of regular use of an inhaled betaagonist in subjects stratified by genotype for the beta-adrenergic receptor, a study of the efficacy of a leukotriene pathway antagonist in enabling reduction or elimination of inhaled corticosteriod therapy in subjects with mild or moderate persistent asthma, and other studies illustrated briefly in this application, but modified or replaced by the ACRN Steering Committee in response to new information or the release of new forms of therapy. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen

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Project Title: ASTHMA CLINICAL RESEARCH NETWORK (ACRN) Principal Investigator & Institution: Martin, Richard J.; Department of Medicine; National Jewish Medical & Res Ctr and Research Center Denver, Co 80206

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Timing: Fiscal Year 2002; Project Start 30-SEP-1993; Project End 31-AUG-2004 Summary: This application proposes to continue the participation of investigators at National Jewish Medical and Research Center in an interactive network of six centers, the Asthma Clinical Research Network (ACRN) in conducting studies of novel therapies for asthma and in disseminating findings to the practicing community. The need for such a network was suggested by increases in the mortality, morbidity, prevalence, and costs of asthma, by research studies showing that asthma is linked to airway inflammation, and by the accelerating rate of development of potentially effective, but also potentially costly treatments. Defining the place of these new therapies was seen as requiring collaborative, multi-center studies examining subjects reflecting the diversity of the U.S. population. In its first 5 years, the ACRN established an interactive infrastructure and added a research site at Harlem Hospital, New York, which serves a predominantly minority population. The ACRN completed and published trials of the effects of regular use of a Beta- agonist in mild asthma ("BAGS") and of the efficacy of colchicine as an alternate to an inhaled corticosteroid (ICS) in moderate asthma. It is now conducting trials comparing a long-acting Beta-agonist, an ICS, and the combination of the two in moderate to severe asthma. We are about to start a 5th study to establish doses of different ICS with equivalent effects on cortisol secretion. These studies have been presented at meetings of the ATS, ACCP, and AAAAI, as have 10-12 ancillary studies analyzing the performance of clinical research. The ACRN has also reported its findings from subgroup analysis of the "BAGS" study: that subjects with different genotypes for the Beta-adrenergic receptor are differently affected by regular use of albuterol. This application proposes continued participation of the National Jewish Asthma Clinical Research group in the multicentered, collaborative trials of the ACRN. The studies proposed include a comparison of the clinical efficacy of doses of different inhaled corticosteroids with equal systemic effects, a prospective study of regular use of an inhaled Beta-agonist in subjects stratified by genotype for the Betaadrenergic receptor, a study of the efficacy of a leukotriene pathway antagonist in enabling reduction or elimination of inhaled corticosteroid therapy in subjects with mild or moderate persistent asthma, and other studies illustrated briefly in this application, but modified or replaced by the ACRN Steering Committee in response to new information or the release of new forms of therapy. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •

Project Title: ASTHMA CLINICAL RESEARCH NETWORK CENTER Principal Investigator & Institution: Boushey, Homer A.; Professor of Medicine; Cardiovascular Research Inst; University of California San Francisco 500 Parnassus Ave San Francisco, Ca 941222747 Timing: Fiscal Year 2002; Project Start 30-SEP-1993; Project End 31-AUG-2004 Summary: This application proposes to continue the participation of investigators at UCSF in an interactive network of six centers, the Asthma Clinical Research Network (ACRN) in conducting studies of novel therapies for asthma and in disseminating findings to the practicing community. The need for such a network was suggested by increases in the mortality, morbidity, prevalence, and costs of asthma, by research studies showing that asthma is linked to airway inflammation, and by the accelerating rate of development of potentially effective, but also potentially costly treatments. Defining the place of these new therapies was seen as requiring collaborative, multicenter studies examining subjects reflecting the diversity of the U.S. population. In its first 5 years, the ACRN established an interactive infrastructure and added a research site at Harlem Hospital, New York, which serves a predominantly minority population.

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The ACRN completed and published trials of the effects of regular use of a Beta-agonist in mild asthma("BAGS") and of the efficacy of colchicine as an alternate to an inhaled corticosteroid (ICS) in moderate asthma. It is now conducting trials comparing a longacting Beta-agonist, an ICS, and the combination of the two in moderate to severe asthma. We are about to start a 5th study to establish doses of different ICS with equivalent effects on cortisol secretion. These studies have been presented at meetings of the ATS, ACCP, and AAAAI, as have 10-12 ancillary studies analyzing the performance of clinical research. The ACRN has also reported its findings from subgroup analysis of the "BAGS" study: that subjects with different genotypes for the Beta-adrenergic receptor are differently affected by regular use of albuterol. This application proposes continued participation of the UCSF Asthma Clinical Research group in the multicentered, collaborative trials of the ACRN. The studies proposed include a comparison of the clinical efficacy of doses of different inhaled corticosteroids with equal systemic effects, a prospective study of regular use of an inhaled Beta-agonist in subjects stratified by genotypes for the Beta-adrenergic receptor, a study of the efficacy of a leukotriene pathway antagonist in enabling reduction or elimination of inhaled corticosteroid therapy in subjects with mild or moderate persistent asthma, and other studies illustrated briefly in this application, but modified or replaced by the ACRN Steering Committee in response to new information or the release of new forms of therapy. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •

Project Title: BIOPHYSICAL MELANOCYTES

MECHANISMS

IN

LEUKOCYTES

AND

Principal Investigator & Institution: Malawista, Stephen E.; Professor of Medicine; Internal Medicine; Yale University 47 College Street, Suite 203 New Haven, Ct 065208047 Timing: Fiscal Year 2002; Project Start 01-JUN-1977; Project End 31-AUG-2004 Summary: This abstract is not available. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •

Project Title: CHARACTERIZATION OF CANDIDA ALBICANS MICROTUBULES Principal Investigator & Institution: Wilson, Leslie; Professor; Biological Sciences; University of California Santa Barbara 3227 Cheadle Hall Santa Barbara, Ca 93106 Timing: Fiscal Year 2002; Project Start 15-MAY-2001; Project End 30-APR-2004 Summary: Candida albicans, an opportunistic pathogen, can cause vaginal, oral and lung infections in immunocompromised individuals and systemic tissue damages in acquired immunodeficiency patients. The chemotherapy of C. albicans infections is limited because of the strong similarities between C. albicans cells and human cells. However, the mitotic spindles in mammalian and Candida cells are constructed differently. In addition, significant differences exist in the sequences of fungal and mammalian tubulins, which are the building block units of mitotic spindles. Little information is available at biochemical and functional levels about Candida tubulin, and virtually nothing is known regarding the polymerization and dynamics properties of Candida microtubules. The thinking is that understanding the differences between fungal cell tubulin and mammalian tubulin could lead to development of new and selective drugs for the treatment of fungal diseases. Therefore, it is proposed to develop a large-scale purification strategy for C. Albicans tubulin based upon previous success in this laboratory with tubulin from Saccharomyces cerevisiae. The tubulin will be

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characterized biochemically, and the polymerization and dynamic properties of Candida microtubules determined. Finally, the mechanism of interaction of two known microtubule-targeted antifungal drugs (benomyl and griseofulvin) with the Candida tubulin will be determined and the mechanisms by which the drugs modulate the polymerization and dynamics properties of the tubulin will be elucidated. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •

Project Title: COLCHICINE IN THE TREATMENT OF PULMONARY FIBROSIS Principal Investigator & Institution: Rom, William N.; New York University School of Medicine 550 1St Ave New York, Ny 10016 Timing: Fiscal Year 2002 Summary: This abstract is not available. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen

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Project Title: COLCHICINE THERAPY IN CHILDHOOD CIRRHOSIS Principal Investigator & Institution: Sokol, Ronald J.; Professor; University of Colorado Hlth Sciences Ctr P.O. Box 6508, Grants and Contracts Aurora, Co 800450508 Timing: Fiscal Year 2002; Project Start 01-MAR-2002; Project End 28-FEB-2003 Summary: This abstract is not available. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen

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Project Title: CYTOGENETICS OF MEIOSIS OF MAIZE Principal Investigator & Institution: Cande, W Z.; Molecular and Cell Biology; University of California Berkeley Berkeley, Ca 947205940 Timing: Fiscal Year 2002; Project Start 01-AUG-1994; Project End 30-JUN-2003 Summary: Our goal is to understand the mechanism of chromosome segregation during meiosis, particularly how homologous chromosomes pair and synapse. The maize male meiocyte is the only system where there is a large collection of mutants that affect meiosis, and it is possible to do superb cytology. We have collected 3-D images on a deconvolution light microscope system using fluorescence in situ hybridization (FISH) probes and antibodies against RAD51 to describe the rearrangements of telomeres, chromosomes and the recombination machinery during the homology search. There is no premeiotic association of homologs; rather, homologous chromosomes approach each other at the end of leptotene as telomeres associate with the nuclear envelope (NE) and cluster (bouqet formation). We will use FISH probes which light up multiple spots on one specific chromosome arm, FISH centromere specific probes, and antibodies against the recombination machinery (RAD51, MSH2/6) to analyze in 3-D homolog alignment as pairing is initiated. Analysis of the pairing behavior of chromosomal derivatives deficient in synapsis such as rings, deficiency heterozygotes, ditelocentrics and reciprocal translocations will allow us to test the requirements for chromosome ends, telomeric sequences, and subtelomeric or internal homology, for successful pairing. We will analyze the pairing behavior of chromosomes in mutants known to be deficient in the early stages of the homology search (afd, dsy1) or in later stages (as1, dy1, dsy2, etc.). We are developing novel screens based on partial pollen abortion or altered recombination rates to find new meiotic mutants. We are using directed transposon tagging to clone new mutants or existing mutants which are defective in pairing. We assume that the homology search is dependent on the active movement of chromosomes, mediated by telomere-NE associations. We will analyze homolog

12

Colchicine

alignment and telomere clustering in living meiocytes using large blocks of heterochromatin (knobs) as markers. Colchicine blocks telomere interactions with the NE in vitro. We will analyze how colchicine disrupts other aspects on nuclear organization such as nuclear pore distribution. Meiosis is essential for all sexually reproducing organisms and the studies described here will further our understanding of this process not only in maize but in all organisms. The mechanism of meiosis is a topic of major medical interest inaccurate chromosome segregation (aneuploidy) during meiosis is casual in several congenital malformations, a major cause of premature termination of pregnancy, and of poor gamete production in humans. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •

Project Title: DEPRESSION, 5-HT1A RECEPTOR & NEUROPLASTICITY Principal Investigator & Institution: Azmitia, Efrain C.; Biology; New York University 15 Washington Place New York, Ny 10003 Timing: Fiscal Year 2002; Project Start 01-APR-1997; Project End 30-NOV-2005 Summary: (Adapted from applicant's abstract) Depression is associated with affective and cognitive disorders. The applicant suggest some of these symptoms may be due to loss of hippocampal and cortical morphology (cytoskeletal collapse) induced by loss of serotonin. Loss of serotonin in the adult rat brain produces decreased dendritic length, dendritic spine number and size, synapse number and a reduction in immunoreactivity to antibodies against neuronal (Microtubule Associated Protein-2 and synaptophysin) and glial (S-lOOn) markers. Injection with a 5-HT1A antagonist produces similar loss of synapses and dendritic spines. The loss of neuronal and glial markers is reversed by treatment with 5-HTIA receptor agonists and S-100beta. This renewal application will test the hypothesis that the 5-HT1A receptor stabilize the neuronal cytoskeletal by targeting neurons and glial cells, and may protect neurons from death (apoptosis). The applicant would like to continue and expand our studies on the effects of 5-HT drugs on morphological reversal after 5-HT loss proposed in the onginal grant. In addition, the applicants now propose the 5-HT1A receptor may regulate the cytoskeleton of neurons, by acting both on glial (availability of S100f3) and neurons (receptor-induced changes in phosphorylation pathways (e.g. PKC, PKA and MAPK)). In addition, The applicant would like to test if 5-HT1A receptor stimulation or S lOObeta treatmnent will restore the cytoskeleton after exposure to coichicine. Coichicine promotes microtubule disassembly and promotes apoptosis in culture and in vivo. Rats will be injected with para-chloroamphetamine (PCA) to reduce 5-HT levels The applicant will treat these rats with either a 5-HT1A receptor antagonist, tricyclics, serotonin specific reuptake inhibitors (SSRJ) or MAO-A inhibitor. In addition, the applicants will study possible mechanisms of action after exposure of cultured neurons to 5-HT1A receptor agonist and S-lOObeta. The applicants hope to extend this work to primary hippocampal and cortical neuronal and glial cultures using wild type and knockout (S100beta and the 5HT1A receptor) mice. Finally, the actions of S-HT1A agonist and S-lOObeta will be studied after microinjections of colchicine into the adult rat hippocampus and cortex. The applicant will focus on dendritic collapse and apoptosis of neurons. This work will continue our long-term research into the interactions between serotonin and adult neumplasticity. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen

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Project Title: ENHANCING RADIATION THERAPY: VASCULAR TARGETING AGENTS Principal Investigator & Institution: Siemann, Dietmar W.; Professor and Associate Chair for Resear; Radiation Oncology; University of Florida Gainesville, Fl 32611 Timing: Fiscal Year 2002; Project Start 24-JAN-2000; Project End 30-NOV-2003 Summary: This abstract is not available. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen

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Project Title: DISEASE

ENVIRONMENTAL CAUSES

OF

SPORADIC

ALZHEIMER'S

Principal Investigator & Institution: Charlton, Clivel G.; Professor and Chairman; Meharry Medical College 1005-D B Todd Blvd Nashville, Tn 37208 Timing: Fiscal Year 2003; Project Start 01-AUG-2003; Project End 31-JUL-2007 Summary: This study will test a proposition that environmental toxins are involved in the cause of Sporadic AIzheimer's disease (AD) by inducing, early in life, a less resilient but functional set of Nucleus Basalis of Meynert (NBM) acetylcholinergic (Ach) neurons that cannot withstand the stress placed on them later in life. Two stages of afflictions, therefore, are involved. The 1st is a predisposing or sensitizing stage that occurs early in life, causes mostly epigenetic changes that impair the phenotype and/or reduce the number of the NBM Ach neurons. The 2nd superimposing/precipitating stage occurs when age-related wear-and-tear or other interventions damage the already susceptible NBM neurons and precipitate AD. The project will identify interventions that will mimic the two stages. The plant-derived tubulin assembling inhibitors, colchicines; the fungal-derived protein synthesis inhibitor, puromycin, and the fungal and plantsderived mitochondrial toxin, 3-nitroproprionic acid (3-NP) will be administered during the period of differentiation of the NBM Ach neurons of the embryos in timed-pregnant mice to induce the 1st stage. Age-related studies will verify the trans-placental or indirect in utero changes related to memory functions and the anatomy and histochemistry of the NBM Ach neurons, thus testing the vulnerability of the neurons to the wear-and-tear of life. The anticholinergic agent, scopolamine, that causes amnesia will be used, also, to mimic the 2nd stage and rationally to precipitate Alzheimer's disease-like changes in the pups. It is proposed that the ED50 for the induction of amnesia will be lower in the 1st stage treated mice, as compare to control. A new model for AD may be identified, based on chemically producing a less resilient but functional NBM Ach neuronal phenotype early in life and stressing those susceptible neurons later in life. Interventions that prevent or delay the toxic responses will be tested. This concept is relevant to the role of the environmental in about 90% of AD cases, and it may be used to study other neurodegenerative disorders but focusing on other neuronal sets. The mechanisms that underlie the proposed sensitization and precipitating stages, such as DNA and RNA editing and protein modifications, will be studied in the future. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •

Project Title: HEPATIC DRUG ELIMINATION IN PREGNANCY Principal Investigator & Institution: Vore, Mary E.; Professor and Director; Toxicology; University of Kentucky 109 Kinkead Hall Lexington, Ky 40506 Timing: Fiscal Year 2002; Project Start 30-SEP-1979; Project End 31-MAY-2006 Summary: (provided by applicant): This proposal focuses on the effects of estradiol and its metabolites on the function and expression of Mrp2 (ABCC2), the ABC transporter

14

Colchicine

that mediates the biliary excretion of glucuronide and glutathione conjugates from the hepatocyte into bile. The proposal builds on our findings that 1) Mrp2-mediated transport of estradiol-17Beta-(Beta-D-glucuronide) (E217G) is essential for its cholestatic activity, 2) E217G causes endocytic retrieval of Mrp2 from the canalicular membrane that coincides with decreased bile flow, and 3) expression of Mrp2 protein, but not Mrp2 mRNA, is decreased in pregnancy. Aim 1 will test the hypothesis that transport of cholestatic E217G and the choleretic estradiol-3-glucuronide (E23G) by rat Mrp2 and human MRP2 is mediated by overlapping but non-identical substrate binding sites. We will use an Mrp2/MRP2 baculovirus expression system in Sf9 cells and probe the substrate binding sites of E217G vs E23G. We will also determine if women with intrahepatic cholestasis of pregnancy have polymorphisms in MRP2 that alter their transport of E217G vs E23G. Aim 2 will test the hypotheses that A) E217G causes endocytic retrieval of Mrp2 and other transporters critical to bile formation from the canalicular membrane leading to inhibition of flow, and B) agents that protect against cholestasis do so by either inhibiting Mrp2 transport of E217G or prevention of transporter retrieval. We will use confocal immunomicroscopy to monitor endocytic retrieval of transporters from and their exocytic insertion into the canalicular membrane. Aim 3 will characterize the changes in Mrp2 expression in pregnancy and test the hypotheses that A) estrogens mediate the decreased hepatic Mrp2 expression in pregnancy, B) Mrp2 is subject to transcript-specific translational control conferred by regulatory elements in the 5' or 3' untranslated regions of Mrp2 mRNA and C) pregnancy and estrogens increase the degradation of Mpr2 protein. We will use polysomal distribution analysis of Mrp2 mRNA, translation assays in HepG2 cells and determine the degradation half-life of Mrp2 protein in control, pregnant, and estrogentreated rats. Significance: Characterization of the mechanisms by which estrogens decrease Mrp2/MRP2 function and expression can lead to 1) improved drug therapy for women in pregnancy, 2) development of therapeutic measures to increase MRP2 function in cholestatic liver disease, and 3) methods to screen for cholestatic toxicity in drugs under development. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •

Project Title: INHIBITOR OF FTSZ POLYMERIZATION IN M. TUBERCULOSIS Principal Investigator & Institution: Reynolds, Robert C.; Southern Research Institute Birmingham, Al 35205 Timing: Fiscal Year 2002; Project Start 15-JUN-2002; Project End 31-MAY-2005 Summary: (Provided by the applicant): Development of new antitubercular agents is of critical importance worldwide. Our program has identified a new class of inhibitor of Mycobacterium tuberculosis(Mtb) that inhibits a novel protein not presently targeted by current antitubercular agents. The 2-alkoxy-carbonylamino-pyridines (2-ACPs) potently inhibit the growth of Mtb with an MIC99 (SRI-3072) as low as 0.15 microgram/ml (0.28 micromolar). Furthermore, SRI-3072 shows bactericidal activity, and shows significant activity in a murine-derived macrophage model with an EC90 & EC99 of 0.12 and 1.42 microgram/ml respectively. These analogs also show selective activity against Mtb versus a mammalian cell line. This program has successfully identified the target of these agents, the mycobacterial tubulin homolog FtsZ. The target protein has been cloned, expressed and isolated in quantities sufficient for development of in vitro polymerization and GTP hydrolysis assays. Three compounds, SRI-3072, SRI-76 14, and colchicine have been shown to inhibit polymerization of Mtb FtsZ in a dose dependent manner with IC50S of 50 uM, 60 uM, and 100 uM respectively. Furthermore. we have shown that SRI-7614 affects Mtb FtsZ polymerization by electron microscopy. SRI-7614

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has also been shown to be active vs. a panel of single drug-resistant Mtb strains. We currently have crystal structures of Mtb FtsZ bound to citrate, GTPgS, and GDP. To date, about 200 2-ACP analogs have been screened in vitro against Mtb H37Rv. We have developed a SAR profile that will allow the preparation of more selective and more potent antitubercular agents. In this application, we propose to continue development of the 2-ACP class through preparations of new analogs of the more potent and selective subclasses, the 3-deaza-pteridines (priority), and the pyridodiazepines (backup). We will carefully evaluate these compounds for activity and selectivity in various in vitro assays including an in vitro Mtb H37Ra assay, an in vitro Mtb FtsZ polymerization and GTPase assay, an in vitro tubulin polymerization assay and a mammalian cell toxicity assay. Selected active agents will be further screened in an h in vitro macrophage model and a Mtb mouse model. The effect of inhibitors on FtsZ polymerization will be analyzed using electron microscopy. Data from the biological screening and the EM structural studies will feed back into compound design in an interactive, iterative drug design cycle that critically focuses on antibacterial potency and selectivity. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •

Project Title: INTERLEUKIN 6 ROLE IN ALCOHOLIC LIVER CIRRHOSIS Principal Investigator & Institution: Rojkind, Marcos; Research Professor; T.R.U.E. Research Foundation 8610 N New Braunfels, Ste 705 San Antonio, Tx 78217 Timing: Fiscal Year 2002; Project Start 01-APR-1995; Project End 31-MAR-2005 Summary: (Adapted from the Investigator's Abstract): Alcohol-induced liver cirrhosis is a leading cause of death worldwide and accounts for over 50 percent of all deaths due to cirrhosis. There is no proven therapy for this deadly disease and, therefore, multiple attempts are being made at developing novel anti-fibrogenic agents based on the current knowledge of the pathophysiology of the disease. Both local and systemic events play a key role in the development of liver cirrhosis. At a local level, are fibrogenic and induce the expression of type I collagen genes by hepatic stellate cells. These cells are in controlling portal blood flow, producing excess type I collagen and contracting the wound. Liver macrophages and inflammatory cells produce the cytokines and growth factors that play a key role in activating hepatic stellate cells to make scar tissue. At the systemic level, the general response of the organism to non-factor-alpha and inteleukin6, which are produced during the acute phase, play a key role in priming hepatic stellate cells to proliferate and make type I collagen. The investigator's long-term goals are to define molecular mechanisms whereby ethanol induces liver fibrosis and to develop novel and more rational anti-fibrogenic therapies based on these findings. In this application they propose experiments to unravel basic molecular events whereby the acute phase in general, and tumor necrosis factor-alpha and interleukin-6 in particular, contribute to the fibrogenic process. Thus, the PI will use modern techniques in cell and molecular biology to unravel signal transduction pathways involved in the activation of hepatic stellate cells and in establishing pathways through which the acute phase cytokines enhance the fibrogenic actions of acetaldehyde. Moreover, the investigators will test whether colchicine, an anti-inflammatory drug with anti-fibrogenic potential that ameliorates live cirrhosis has an effect on the parameters to be investigated. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen

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Project Title: INTRINSIC ANATOMY OF THE CIRCADIAN RHYTHM SYSTEM Principal Investigator & Institution: Morin, Lawrence P.; Professor; Psychiatry and Behavioral Scis; State University New York Stony Brook Stony Brook, Ny 11794

16

Colchicine

Timing: Fiscal Year 2002; Project Start 01-AUG-2002; Project End 31-JUL-2006 Summary: (provided by applicant): The clock governing such mammalian circadian rhythms as the sleep-wake or activity-rest cycles is located in the hypothalamic suprachiasmatic nucleus (SCN). Recently, several studies have demonstrated that areas within a single SCN oscillate out of phase with respect to one another. In order to properly understand the spatial issues relating to phasic activity at the cellular level in the SCN, it is necessary to have a careful description of the SCN itself. Despite the very large volume of literature on the topic, there has been no complete, three dimensional evaluation of the SCN intrinsic anatomy in any species. The vast majority of studies have used adjacent tissue sections to compare relative spatial locations of cell types within the nucleus; many fewer experiments have employed double label methods to determine whether individual cells contain two distinct neuromodulators. The proposed work will use immunohistofluorescence techniques to study combinations of three labels in order to determine their specific locations in the SCN. Importantly, all the work will be performed with animals pretreated with colchicine.Preliminary data show that all SCN neurons are darkly immunoreactive for GABA. This neuromodulator will serve to define the nucleus and anchor the locations of cells immunoreactive (IR) to other neuromodulators. There are neuron groups in the hamster SCN immunoreactive to GAGA, substance P, calbindin, calretinin, vasoactive intestinal polypeptide, vasopressin, cholecystokinin, and gastrin releasing peptide. The distribution of GABA cells encompasses the entire nucleus, vasopressin and cholecystokinin neurons occupy a dorsomedial location; substance P, gastrin releasing peptide, calbindin and calretinin cells are found in a central subnucleus; and vasoactive intestinal polypeptide neurons are found in a ventrally located area. There appears to be fairly extensive overlap among certain of the cell distributions. The exact locations of the cell types and their locations of overlap and co-localization of neuromodulator will be determined, and function will be assessed by evaluating co-localization of light-induced protein markers. In addition, the locations of the various cell types will be determined with respect to the terminal fields of the three main SCN-afferent projections, the NPY-IR geniculohypothalamic tract from the intergeniculate leaflet, the serotonin-lR projection from the median raphe nucleus and the retinohypothalamic projection identified by cholera toxin B fragment-IR following an eye injection. Presynaptic terminal identity will be confirmed by the presence of synaptophysin-IR. Work on the hamster will be extended to the mouse and we will determine which cell types exhibit light-induced gene expression in response to nocturnal light exposure. The results will provide the anatomical framework necessary for interpretation of future physiological and molecular experiments. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •

Project Title: MECHANISM OF COMPENSATORY TISSUE REPAIR IN RENAL INJURY Principal Investigator & Institution: Mehendale, Harihara M.; Professor of Pharmacology & Toxicology; Toxicology; University of Louisiana at Monroe 700 University Ave Monroe, La 71209 Timing: Fiscal Year 2003; Project Start 01-JUN-2003; Project End 31-MAR-2007 Summary: (provided by applicant): Renal tissue can respond to loss of tissue by toxic tissue injury by stimulating renal tissue repair. Although the importance of the nephrogenic repair response is generally accepted, biochemical characterization of this process with regard to dose-response relationships, temporal effects, molecular regulation, and effects of modulation of the repair on recovery from renal injury and survival have not been investigated. In spite of the enormous renal reserve capacity,

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toxic renal failure and death can occur due to renal insufficiency. Clinicians would welcome life saving therapies that may help them in restoring renal function by replacing the lost tissue with functional tissue. This proposal is to investigate the mechanism of renal tissue repair using a well-established murine model of nephrotoxicity induced by S-(trans 1,2-dichlorovinyl) L-cysteine (DCVC). Preliminary studies indicate that renal tissue repair is dose-dependent, increases up to a threshold, and is inhibited beyond this threshold dose causing progression of renal injury leading to renal failure and animal death. Ablation of cell division response by administration of colchicine, well after the initiation of renal injury from an ordinarily non-lethal dose of DCVC, leads to progression of injury and animal death indicating the pivotal importance of cell division in tissue repair and recovery from limited initial injury. Furthermore, administration of a low dose of DCVC (15 mg/kg) 72 h before giving a normally lethal dose of DCVC resulted in complete protection from mortality (autoprotection), suggesting that preplaced tissue repair can avert renal failure and death. In these experiments, the possibility of protection by induction of metallothionein and priming dose will be fully tested. Objective of this proposal is to test the hypothesis that timely and adequate stimulation of cell division and tissue repair determines the toxic outcome of renal injury. The specific aims are to: a) investigate the mechanism of autoprotection b) investigate if pretreatment by a low dose of mercuric chloride can protect mice (heteroprotection) from a lethal dose of DCVC; c) investigate if depletion of ATP underlies the reason for loss of cell division after a high dose and if restored ATP is the reason for autoprotection; and d) investigate molecular signaling mechanisms following a low dose, high dose, and also in the autoprotection group. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •

Project Title: MECHANISM OF DRUG TRANSPORT IN LUNG CANCER CELLS Principal Investigator & Institution: Awasthi, Sanjay; Professor; Chemistry and Biochemistry; University of Texas Arlington 301 South Center Street Arlington, Tx 76019 Timing: Fiscal Year 2002; Project Start 01-APR-1998; Project End 28-FEB-2006 Summary: We had previously characterized a versatile transporter, DNP-SG ATPase in human tissues, which mediated the AlP-dependent transport of anionic glutathioneconjugates as well as doxorubicin (DOX). Studies in the currently funded project were aimed at structural and functional characterization of DNP-SG ATPase and immunologically related transport proteins with the overall objective of delineating their relevance to MDR. We are pleased to report successful cloning of DNP-SG AlPase, and its functional reconstitution in artificial proteoliposomes. Our studies show that DNP-SG ATPase is identical to RLIP76, a ral-binding GTPase activating effector protein with previously unknown function. Our studies demonstrated that DNP-SG ATPase\RLIP76 is a 76 kDa precursor protein which gives rise to 5 major peptides which can reconstitute an AlP-dependent primary active DOX and glutathione conjugate transporter in artificial liposomes. RLIP76 over-expression confers a drugaccumulation defect and multidrug resistance when expressed in mammalian cells. Antibodies against RLIP76 inhibit DOX transport in lung cancer cells and markedly potentiate its cytotoxicity in a linear, concentration dependent manner at low concentrations. Comparison between SCLC and NSCLC shows that RLI76 is structurally and functionally distinct between SCLC and NSCLC: whereas SCLC express the wildtype RLIP76, NSCLC cells express a variant which has distinct proteolytic susceptibility, greater stability and significantly greater transport activity than RLIP76 from SCLC. Uptake of wild-type RLIP76-proteoliposomes by NSCLC confers a non-adherent morphology similar to that of SCLC. These observations lead us to hypothesize that

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Colchicine

RLIP76 is a multi-drug resistance-mediating precursor protein for an AlP-dependent transporter composed from its peptide fragments, that RLIP76 in NSCLC is more active than that present in SCLC, and that distinct nature/processing of its peptide fragments contributes to the observed differences in drug resistance and transport between SCLC and NSCLC. We propose to test our hypothesis through specific aims of 1) establishing that RLIP76 is a versatile AlP-dependent transporter of structurally diverse chemotherapeutic drugs, 2) demonstrating structure/function relationships for RLIP76 and its derived peptides, 3) comparing the function of RLIP76 as a drug and GS-E transporter in SCLC and NSCLC, 4) demonstrating that RLIP76 confers an MDR phenotype in lung cancer cells, and 5) demonstrating that limited tryptic peptides of RLIP76 can distinguish SCLC from NSCLC. These observations provide a potentially clinically relevant therapeutic target for lung cancer, and provide fundamental insight into the role in SCLC and NSCLC of drug-transport, signaling and GSH-linked biochemical pathways. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •

Project Title: MECHANISMS MODULATION

OF

INHIBITORY

GLYCINE

RECEPTOR

Principal Investigator & Institution: Thio, Kwee L.; Neurology; Washington University Lindell and Skinker Blvd St. Louis, Mo 63130 Timing: Fiscal Year 2002; Project Start 01-JUN-2002; Project End 31-MAY-2007 Summary: K. Liu Lin Thio, MD, PhD is a pediatric epileptologist who is interested in developing a research career in ion channel modulation because of its importance to understanding and treating neurological diseases such as epilepsy. He has extensive experience with cellular neurophysiology but would like to probe the molecular mechanisms underlying ion channel modulation. This requires that he learn the basic techniques of molecular biology, which is one of the goals of this proposal. Several neurological disorders including epilepsy may result, in part, from cortical inhibitory glycine receptor (GlyR) dysfunction. Thus, GlyR modulation is important to understanding and treating neurological disease. Although several modulators of GlyR have been identified, their mechanisms of action are unknown because quantitative pharmacological and electrophysiological studies have not been performed. This study proposes to test three hypotheses regarding the mechanism by which three known GlyR modulators act: 1) GlyR and gamma-aminobutyric acidA (GABAA) receptors interact through the cytoskeleton; 2) Sulfhydryl reducing agents inhibit GlyR by chelating extracellular zinc; 3) Potentiation and inhibition of GlyR currents by barbiturates occur at distinct sites. These hypotheses will be tested by studying the electrophysiological properties of native GlyR in cultured embryonic mouse hippocampal neurons and GlyR expressed at Xenopus oocytes and human embryonic kidney (HEK) 293 cells. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •

Project Title: NEUROTROPHINS IN OLFACTORY DEVELOPMENT Principal Investigator & Institution: Guthrie, Kathleen M.; Biomedical Sciences; Florida Atlantic University Boca Raton, Fl 33431 Timing: Fiscal Year 2002; Project Start 01-AUG-1998; Project End 31-JUL-2004 Summary: (Adapted From The Applicant's Abstract) Neurotrophins are known to contribute to critical developmental processes in the nervous system. Recent studies by the applicant have shown that neurotrophins are expressed in the developing mammalian olfactory epithelium during the time that synaptic connections are being

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made with the developing forebrain. At this time, cells in the rostral telencephalon express the appropriate tyrosine kinase trk receptors for these neurotrophins and the olfactory bulbs begin to form. The spatial and temporal patterns of expression suggest the hypothesis that developing sensory neurons in the olfactory epithelium anterogradely transport specific neurotrophin factors to responsive forebrain neurons and thereby contribute to development of the olfactory bulb. The goals of the proposed research are to test aspects of this hypothesis. The first specific aim is to identify the specific cell types expressing different neurotrophins and their receptors in the epithelium and bulb. In particular we wish to determine if neurotrophin mRNAs are expressed by olfactory sensory neurons and if neurotrophin proteins are localized within olfactory nerve projections. Cell types will be identified by colocalization of neurotrophin/receptor mRNA and protein with phenotypic markers specific for subpopulations of olfactory cells The second aim is to determine if the olfactory nerve anterogradely transports neurotrophins from the epithelium to the bulb, and if this has functional consequences. Studies will determine if colchicine treatment increases neurotrophin immunoreactivity in sensory neurons while decreasing immunoreactivity in olfactory axons and terminals. We will also evaluate the redistribution of radiolabeled neurotrophins applied to the olfactory epithelium, and measure levels of bulb trk phosphorylation following such treatment. The third aim is to determine if early neurotrophic factor deprivation leads to morphological or phenotypic abnormalities in the bulb. This will be accomplished by evaluating olfactory system development in mice carrying targeted mutations in neurotrophin genes. The levels, distribution and cellular localization of neurotrophin and trk expression, and of phenotypic cell markers, will be examined in the normal and neurotrophin-deprived olfactory system. Differences in patterns of cell death in forebrain and bulb neuron morphology will also be examined. The final aim is to determine if early neurotrophin deprivation has functional consequences in this system by evaluating bulb trk phosphorylation and odorstimulated c-fos expression in knockout mice and control littermates. Results of these studies will contribute to our understanding of the molecular signals that regulate mammalian forebrain development. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •

Project Title: PATHOBIOLOGY OF NEURODEGENERATIVE DISEASES LINKED TO TAU GENE MUTATIONS Principal Investigator & Institution: Yen, Shu Hui.; Mayo Clinic Coll of Med, Jacksonville Mayo Clinic Jacksonville Jacksonville, Fl 322243899 Timing: Fiscal Year 2002 Summary: Alzheimer's disease (AD) and other neurodegenerative disorders including Pick's disease, progressive supranuclear palsy (PSP), corticobasal degeneration (CBD) and some cases of frontal temporal dementia (FTD) are characterized histopathologically by inclusions in cerebral neurons and glia. The inclusions consists of microtubule associated protein, tau. In contrast to normal brain tau, which is a soluble protein capable of promoting the polymerization of tubu7lin to form microtubules (MT) and of stabilization of MT, tau in inclusions is in filamentous form. The mechanism(s) involved in formation of tau polymers remains to be elucidated. Recent genetic studies have linked tau mutations to a number of FTD with parkinsonism (FTDP-17) as the cause of taopathy. Several missence mutations (e.g. G272V, N279K, P301L, V337M and R406W) and mutations in the 5 splice site of exon 10, which encodes the second tandem repeat, have been identified. The latter mutations result in an increase of the ratio of four to three repeat tau. Whether the presence of mutant tau or the presence of an abnormal

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proportion of four and three repeat tau us sufficient for neuron and/or glia to form tau inclusion remains unclear at present. Moreover, it remains unclear if the function of tau is compromised by these mutations, iv various mutations have different effects, or if these mutations alter the susceptibility of neurons to degeneration. To examine these issues focusing on mutants identified in FTDP-17, (ii0 determine if mutant and wild type tau differ in polymerization potential, susceptibility to proteolysis and other physico-chemical properties, (iii) study the response of cultured cells and mutation in tau gene as well as tau in transgenic animals generated by Projects 3 and 4, and (v) study neuronal and glial cultures of transgenic animals and determine if cells from mice with mutant tau differ from those will wild type tau in response to (a) microtubule destabilizing agent colchicine, (b) phosphatase inhibitors, and (c) oxidant stress. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •

Project Title: PROTEOMICS AND BIOMARKERS FOR HEPATOCELLULAR CANCER Principal Investigator & Institution: Afdhal, Nezam H.; Associate Professor of Medicine; Beth Israel Deaconess Medical Center St 1005 Boston, Ma 02215 Timing: Fiscal Year 2003; Project Start 25-SEP-2003; Project End 31-AUG-2005 Summary: (provided by applicant): Hepatitis C (HCV) is the commonest cause of chronic hepatitis, cirrhosis and hepatocellular carcinoma (HCC) in the United States. HCC occurs primarily in patients with advanced fibrosis and cirrhosis from HCV. Current screening techniques involve the use of serum alfafetoprotein and liver imaging with ultrasound performed in high risk patients on a 3 to 6 monthly basis. Early detection can improve outcomes with liver transplantation and perhaps non-surgical therapies. However screening is not very effective and many patients present with large tumors or multifocal HCC with a median survival of only 6 months. There is a definite clinical need for better non-invasive biomarkers for HCC which can lead to early detection and treatment. The specific aims of this exploratory R21 proposal are to utilize a proteomic approach to identify novel biomarkers for HCC and then evaluate these biomarkers in a cohort of patients with HCV at high risk for HCC. The initial step will be identification of a matching group of patients with a high risk of HCC and those who have developed HCC during the prospective COPILOT study. The COPILOT study provides a large cohort of patients with HCV and cirrhosis who are randomized to treatment with either low dose PEGylated interferon alfa 2b or colchicine and are followed for 4 years with rigorous clinical screening for HCC. The study is in year 2 and the incidence of HCC is approximately 5%. Serum from these patients prior to and after the development of HCC is stored and will be utilized for proteomic studies. Tissue from normal liver and HCC is available from these patients who have undergone liver transplant. A control disease serum bank from patients with HCC unrelated to HCV is also available at BIDMC. The serum and tissue will be examined by proteomics for identification of novel biomarkers using SELDI-TOF mass spectrometry. Careful clinical characterization and matching will assist in the bioinformatic approach necessary to identify candidate biomarkers. Novel proteins and peptide biomarkers will be sequenced and identified and an ELISA will be developed for any promising candidate biomarkers. The candidate biomarker ELISA will then be validated in the large HCV serum bank at BIDMC of patients with all stages of HCV and those in the COPILOT trial. These studies may lead to identification of more specific and sensitive biomarkers for HCC in HCV which can then be validated further in prospective clinical trials. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen

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Project Title: RELEASE AND MOLECULAR COMPOSITION OF MAMMALIAN SFS Principal Investigator & Institution: Fissore, Rafael A.; Veterinary and Animal Sciences; University of Massachusetts Amherst 408 Goodell Building Amherst, Ma 01003 Timing: Fiscal Year 2003; Project Start 01-SEP-2003; Project End 30-JUN-2005 Summary: (provided by applicant): Fertilization in mammalian eggs is characterized by the presence of intracellular calcium ([Ca2+]i) oscillations that are responsible for inducing egg activation. How the sperm initiates and sustains these oscillations is not known, although recent evidence, including that from intracytoplasmic sperm injection experiments (ICSI), suggests that the sperm may release into the ooplasm, after fusion, a [Ca2+]i oscillation-inducing factor (SF). The long-term goal of the laboratory is to isolate and purify the sperm's Ca 2+ active molecule, and the present specific aims will ascertain the temporal release and cellular targeting of SF and the molecular composition of the different Ca 2+active fractions in sperm. Specific Aim 1: To investigate the temporal release of SF. The hypothesis will be examined that SF becomes rapidly dissociated from the sperm head to induce persistent oscillations and then, at the time of pronuclear (PN) formation, it associates with pronuclear (PN)/peri-PN structures, the targeting for which is received at the time of release. To test this hypothesis, Hoechst-labeled sperm heads will be removed from fertilized eggs, and the persistence of oscillations in these eggs monitored in the presence of colcemid. Association of SF with the PN in enucleated eggs will be evaluated by the presence of a [Ca2v]i rise at PN-envelope breakdown, which will be induced by exposure to okadaic acid. Specific Aim 2: To investigate the molecular composition of the different sperm Ca 2+ active preparations. The hypothesis will be studied that distinct sperm Ca 2+ active fractions, i.e. soluble SF and less soluble (Triton X-100 and pH-soluble) SFs, share biochemical properties and may have, in fact, a common Ca 2v active molecule(s). Biochemical fractionation will be carried out using column chromatography, and affinity precipitation using biotinylated peptide A7, which depletes Ca 2v activity from SF. Sequencing of significant polypeptide bands will be performed after SDS-PAGE by Matrix Assisted Laser Desorption-Mass Spectrometry. The presence and function of phospholipase C (PLC) zeta, a novel testis PLC, will be assessed by Western blotting and depletion of the molecule from the fractions. Significance: 1) Results from these aims will provide the first description of temporal release of SF during fertilization, and will establish the polypeptide composition of all the Ca 2vactive preparations in sperm, which will lead to the identification of SF; 2) It will be possible to assess the physiological relevance and impact of sperm manipulations on the pattern of oscillations initiated by ICSI, a technique commonly used to treat human male infertility, which has been shown to have detrimental effects on development, and some of which may be due to activation defects. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen

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Project Title: REMOTE VIRAL GENE DELIVERY IN A MOUSE MODEL OF ALS Principal Investigator & Institution: Mobley, Bret C.; Neurology; University of Michigan at Ann Arbor 3003 South State, Room 1040 Ann Arbor, Mi 481091274 Timing: Fiscal Year 2002; Project Start 01-APR-2002 Summary: The goal of the experiments outlined in this proposal is to characterize remote gene delivery to the spinal cored and brainstem of the superoxide dismutase (SOD1) mouse, an animal model of ALS, using adeno- associated virus. We will utilize viral vectors whose gene products are marker proteins, either beta-galactosidase or

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green fluorescent protein (GFP). After peripheral injection of vector into either the mouse sciatic nerve or brachial plexus, we will examine the corresponding CNS gene expression. We expect remote delivery of recombinant genes to the CNS through peripheral nervous system (PNS) injection to offer a number of potential advantages over direct CNS injections, including minimally invasive delivery of viral vectors with the potential for repeated treatments and a reduced inflammatory response. We hope to quantify gross GFP and beta-glactosidase expression in this study as well as discover biases in terms of which CNS cell types express these proteins. We also hope to confirm that retrograde axonal transport, not diffusion, is responsible for spinal cord expression. We will do this by blocking microtubule function with peripheral colchicine injection and also by analyzing beta-galactosidase distribution after injecting the protein peripherally. Our final aims involve observing the effects of remote virus delivery on neuronal cell viability and determining whether later reinjection and also be analyzing beta-galactosidase distribution after injecting the protein peripherally. Our final aim involve observing the effects of remote virus delivery on neuronal cell viability and determining whether later reinjection of vector enhances viral gene expression. Data from this study will aid in elucidating the rational choice of viral vector(s) and mode(s) of delivery for optimal expression of therapeutic proteins in the central nervous system of the ALS mouse model. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •

Project Title: RETINAL NERVE FIBER LAYER REFLECTANCE MECHANISMS Principal Investigator & Institution: Knighton, Robert W.; Associate Professor; Ophthalmology; University of Miami-Medical Box 248293 Coral Gables, Fl 33124 Timing: Fiscal Year 2003; Project Start 01-AUG-1990; Project End 30-JUN-2008 Summary: (provided by applicant): The diagnosis and management of glaucoma require sensitive methods for detecting and measuring damage to retinal ganglion cells and their axons. New quantitative methods for optically assessing the retinal nerve fiber layer (RNFL) have begun to deliver enhanced sensitivity and objectivity over previous methods and are moving toward routine clinical use. The long-term objectives of this continuation project are a) to provide a comprehensive, quantitative, basic understanding of the optical properties of the RNFL and b) to translate this basic knowledge into practical improvements in clinical assessment of glaucomatous damage. Imaging micropolarimetry, scanning laser polarimetry and optical coherence tomography will be used to pursue the following Specific Aims: 1) Identify the cylindrical structures responsible for the optical properties of the RNFL by characterizing their physical and biological properties. The RNFL behaves as a uniform thick array of approximately parallel light scattering cylinders embedded in a birefringent slab. Reflectance spectra suggest two cylindrical mechanisms, one thin relative to the wavelength and the other thicker. The identities of the cylinders and the mechanism for RNFL birefringence will be determined. 2) Test in vitro three hypotheses about the relation between RNFL birefringence and the structure of nerve fiber bundles. 3) Measure and map RNFL birefringence in humans as a basis for "tissue diagnosis" of the RNFL. Birefringence is an intrinsic property of the tissue, depends directly on RNFL ultrastructure, and may provide a means of early detection of structural damage to ganglion cells in glaucoma. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen

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Project Title: RETROGRADE AMNESIA AFTER HIPPOCAMPAL DAMAGE Principal Investigator & Institution: Sutherland, Robert James.; Professor; University of Lethbridge 4401 University Dr Lethbridge, Ab Timing: Fiscal Year 2002; Project Start 08-AUG-2002; Project End 31-JUL-2007 Summary: (provided by applicant): Memory disorders are probably the most common symptom after any process that disrupts normal medial temporal lobe functioning. The most severe form of disorder involves the loss of ability to form new memories (anterograde amnesia) and the loss of memories from before the damage (retrograde amnesia). Three experiments with rats are proposed which address fundamental properties of the neural mechanisms of retrograde amnesia. The first evaluates the temporal dependence of retrograde amnesia produced by nearly complete, selective hippocampal formation damage caused by multiple microinjections of N-methylDaspartate. Using both a between- and within-subject design, we evaluate the severity of retrograde amnesia for 4 types of information, spatial map, contextual conditioning, configural discriminations, and socially transmitted diet preference. Several intervals between training and hippocampal damage are sampled, between 1 and 64 weeks. Further, we independently test the effects of memory reactivations and subject age at the time of remote learning. Second, we compare the selectivity of the retrograde deficits with anterograde deficits for certain types of information. Anterograde amnesia affects declarative/relational/configural information and not nondeclarative/nonrelational/elemental information. Using variants of 4 tasks involving Morris water task, Pavlovian fear conditioning, socially transmitted diet preference, and transverse patterning we examine this distinction in retrograde amnesia after hippocampal damage. Third, we compare the retrograde gradients and the task specificity with different extents of hippocampal damage, using varying numbers of NMDA microinjections and colchicine dentate gyrus microinjections. The comparisons will address the hypotheses that temporal gradients in retrograde amnesia are related to the amount of spared hippocampal circuitry and that dentate gyrus circuitry contributes only at the time of initial memory acquisition. The results bear upon fundamental aspects of hippocampal dependent, long-term memory consolidation theories and will delineate a more precise role for the hippocampus formation in long-term memory. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen

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Project Title: ROLE OF THE ACETYLTRANSFERASE P300 IN CELLULAR RESPONSES Principal Investigator & Institution: Avantaggiati, Maria L.; Associate Professor of Oncology; Pharmacology; George Washington University 2121 I St Nw Washington, Dc 20052 Timing: Fiscal Year 2002; Project Start 06-AUG-2002; Project End 31-JUL-2007 Summary: (provided by applicant): Drugs that affects the microtubule dynamics constitute one of the most important classes of chemotherapeutic agents. Antimicrotubule drugs of clinical relevance include paclitaxel (taxol), vinca alkaloids (vinblastin and vincrisitn), nocodazole and colchicine. These agents trigger a checkpoint, the spindle checkpoint, which monitors he attachment of chromosomes to the spindle, and elicits arrest in mitosis generally followed by apoptosis. Several cellular factors which participate in this checkpoint have recently been identified, however, the exact molecular mechanisms through which errors in spindle assembly, or chromosomes attachment to the spindle engage the cell cycle machinery remain to be elucidated. We made the novel finding that a transcription coactivator possessing

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acetyltransferase activity, p300, enhances the mitotic arrest elicited by taxol. Acetyltransferases belonging to the p300 family have been implicated in conveying adaptive responses in a variety of signal transduction pathways, through regulation of transcription of many cell-cycle regulatory genes. We now demonstrate that p300 associates with mitotic and interphase microtubules, it acetylates tubulin, and it favors tubulin polymerization in a taxol-dependent assay. Moreover p300 levels and its association with microtubules are significantly increased in taxol treated cells. Based on these results we hypothesize that p300 acts as an important effector of sensitivity of tumor cells to taxol, through its association with tubulin and through its activity as a transcription factor. To test this hypothesis we will: l)Identify the regions of p300 responsible for its interaction with microtubules and generate mutants with corrupted tubulin-binding ability (loss or gain of function, respectively). 2) Study how these mutants influence cytoskeleton architecture, spindle assembly and nuclear import of acetylated transcription factors in taxol treated cells. 3)Define the mechanisms by which p300 participates in cell cycle arrest and apoptosis induced by taxol and identify the molecular events occurring downstream of taxol which are influenced by p300. 4)Provide a rationale and a strategy for the design of molecules, such as peptides which mimics p300 effects on apoptosis, able to enhance chemosensitivity to taxol. Since mitotic spindle inhibitors constitute a growing class of anti-cancer agents, it is essential to understand molecular mechanisms of resistance and sensitivity. Thus, studies proposed in this application are expected to have important clinical implications. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •

Project Title: SYNTHETIC APPLICATIONS OF CARBENE COMPLEXES Principal Investigator & Institution: Wulff, William D.; Professor; Chemistry; Michigan State University 301 Administration Bldg East Lansing, Mi 48824 Timing: Fiscal Year 2002; Project Start 01-DEC-1983; Project End 30-NOV-2003 Summary: The broad scope of the work proposed involves the development of the chemistry of Fischer carbene complexes to the field of organic synthesis and to the synthesis of organic compounds of importance in human health. The reactions of Fischer carbene complexes with alkynes will be examined for the synthesis of the platelet activating factor antagonist phomactin D and for the synthesis of colchicine and allocolchicinoids that have been investigated for the treatment of gout, familial Mediterranean fever and liver cirrhosis. Asymmetric versions of this reaction will also be used to prepare aS,7S and aR,7S isomers of 1 2 - methylcolchinyl methyl ether to test an unresolved issue regarding the stereochemical requirements for binding of colchicine and allocolchicinoids to tubulin. A new strategy for the synthesis of the new anticancer agent eluetherobin will be explored which involves an intramolecular exoselective Diels-Alder reaction as a key step. The aldol reaction of Fischer carbene complexes will be utilized in the first synthesis of the anticancer agent fostriecin and analogs of fostriecin which are more stable and thus more useful in the clinic. The reaction of Fischer carbene complexes with 1,6-enynes will be explored as a method for rapid access to the taxol family of antitumor agents. The the cyclopropanation reactions of chiral carbene complexes will be examined for the synthesis of aminocyclopropanes and for a synthesis of the antitumor agent helenalin which involves a tandem cyclopropanation/Cope rearrangement sequence. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen

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Project Title: TOTAL SYNTHESIS OF BIOACTIVE NATURAL PRODUCTS Principal Investigator & Institution: Cha, Jin K.; Professor; Chemistry; Wayne State University 656 W. Kirby Detroit, Mi 48202 Timing: Fiscal Year 2002; Project Start 01-JUL-1986; Project End 30-JUN-2004 Summary: (verbatim from the applicant's abstract) The proposed program is directed at a total synthesis of a wide range of biologically active medium-sized carbocyclic and heterocyclic natural products. Our objective includes the development and refinement of general synthetic methods which would allow the convenient preparation of natural products and their synthetic derivatives for biological testing. The new key methods include (1) the (4 + 3) cycloadditions of cyclic oxyallyls and heteroatom-substituted oxyallyls; and (2) the low-valent titanium-mediated cyclopropanations of carboxylic acid derivatives and related coupling of imides; subsequent elaboration includes a cascade of free-radical cyclizations. Specific target molecules include the tigliane, daphnane, and ingenane diterpenes of the phorbol family (e.g., phorbol (Ia), prostratin (II), resiniferatoxin (III), or ingenol (IVa)) which possess potent cocarcinogenic, tumor inhibitory, anti-HIV, or analgesic activity; ophiobolins (Va-c) which show interesting inhibitory activities of Ca(2+)-binding calmodulins or angiotensin II receptor binding; tropoloisoquinoline alkaloids of the colchicine family (e.g., gradirubrine (VI), isoimerubrine (VII), and imerubrine (VIII)), which are antimitotic inhibitors; sarains A-C (IXA-IXC), structurally fascinating marine alkaloids, which exhibit antitumor, antibacterial, and insecticidal activity; Cephalotaxus alkaloids (e.g., cephalotaxine (X) and homoharringtonine (XI) having significant antitumor activity); and mitomycin alkaloids (e.g., mitomycin C (XIIC) and FR900482 (XV)) which are clinically important antitumor agents. The target compounds are chosen not only for their useful biological activities, but also to demonstrate the preparative power of the underlying synthetic methodologies that have successfully been developed in our laboratories. Concurrent with these new foci, we will also bring to a successful conclusion some ongoing research projects. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen

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Project Title: TRIAL OF LOW DOSE ORAL PULSE METHOTREXATE VS COLCHICINE Principal Investigator & Institution: Kaplan, Marshall; New England Medical Center Hospitals 750 Washington St Boston, Ma 021111533 Timing: Fiscal Year 2002 Summary: This abstract is not available. 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 Library of Medicine (NLM).4 Access to this growing archive of e-journals is free and 3 4

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

With PubMed Central, NCBI is taking the lead in preservation and maintenance of open access to electronic literature, just as NLM has done for decades with printed biomedical literature. PubMed Central aims to become a world-class library of the digital age.

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unrestricted.5 To search, go to http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=Pmc, and type “colchicine” (or synonyms) into the search box. This search gives you access to fulltext articles. The following is a sample of items found for colchicine in the PubMed Central database: •

2-Methoxyestradiol, an endogenous mammalian metabolite, inhibits tubulin polymerization by interacting at the colchicine site. by D'Amato RJ, Lin CM, Flynn E, Folkman J, Hamel E.; 1994 Apr 26; http://www.pubmedcentral.gov/picrender.fcgi?tool=pmcentrez&action=stream&blobt ype=pdf&artid=43703

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Adjuvant Action of Bacterial Endotoxin and Colchicine on Antibody Formation in the Hamster. by Merritt K.; 1971 Oct; http://www.pubmedcentral.gov/picrender.fcgi?tool=pmcentrez&action=stream&blobt ype=pdf&artid=416319

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B ring regulation of colchicine binding kinetics and fluorescence. by Bhattacharyya B, Howard R, Maity SN, Brossi A, Sharma PN, Wolff J.; 1986 Apr; http://www.pubmedcentral.gov/picrender.fcgi?tool=pmcentrez&action=stream&blobt ype=pdf&artid=323228

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Cell expansion and single-cell separation induced by colchicine in suspensioncultured soybean cells. by Hayashi T, Yoshida K.; 1988 Apr; http://www.pubmedcentral.gov/picrender.fcgi?tool=pmcentrez&action=stream&blobt ype=pdf&artid=280049

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Chemical cross-linking of proteins of Semliki Forest virus: virus particles and plasma membranes from BHK-21 cells treated with colchicine or dibucaine. by Richardson CD, Vance DE.; 1978 Oct; http://www.pubmedcentral.gov/picrender.fcgi?tool=pmcentrez&action=stream&blobt ype=pdf&artid=354258

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Dissociation by Colchicine of the Hexose Monophosphate Shunt Activation from the Bactericidal Activity of the Leukocyte. by DeChatelet LR, Cooper MR, McCall CE.; 1971 Jan; http://www.pubmedcentral.gov/picrender.fcgi?tool=pmcentrez&action=stream&blobt ype=pdf&artid=416108

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Effect of Colchicine on Intestinal Disaccharidases: Correlation with Biochemical Aspects of Cellular Renewal. by Herbst JJ, Hurwitz R, Sunshine P, Kretchmer N.; 1970 Mar; http://www.pubmedcentral.gov/picrender.fcgi?tool=pmcentrez&action=stream&blobt ype=pdf&artid=322501

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Effects of Colchicine and Vinblastine on the Cellular Action of Vasopressin in Mammalian Kidney A POSSIBLE ROLE OF MICROTUBULES. by Dousa TP, Barnes LD.; 1974 Aug; http://www.pubmedcentral.gov/picrender.fcgi?tool=pmcentrez&action=stream&blobt ype=pdf&artid=301552

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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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Expanded distribution of mRNA for nerve growth factor, brain-derived neurotrophic factor, and neurotrophin 3 in the rat brain after colchicine treatment. by Ceccatelli S, Ernfors P, Villar MJ, Persson H, Hokfelt T.; 1991 Nov 15; http://www.pubmedcentral.gov/picrender.fcgi?tool=pmcentrez&action=stream&blobt ype=pdf&artid=52926

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Mechanism of Action of Colchicine in Acute Urate Crystal-Induced Arthritis. by Spilberg I, Mandell B, Mehta J, Simchowitz L, Rosenberg D.; 1979 Sep; http://www.pubmedcentral.gov/picrender.fcgi?tool=pmcentrez&action=stream&blobt ype=pdf&artid=372181

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Molecular basis of preferential resistance to colchicine in multidrug-resistant human cells conferred by Gly-185----Val-185 substitution in P-glycoprotein. by Safa AR, Stern RK, Choi K, Agresti M, Tamai I, Mehta ND, Roninson IB.; 1990 Sep; http://www.pubmedcentral.gov/picrender.fcgi?tool=pmcentrez&action=stream&blobt ype=pdf&artid=54716

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Platelets and Microtubules EFFECT OF COLCHICINE AND D2O ON PLATELET AGGREGATION AND RELEASE INDUCED BY CALCIUM IONOPHORE A23187. by Menche D, Israel A, Karpatkin S.; 1980 Aug; http://www.pubmedcentral.gov/picrender.fcgi?tool=pmcentrez&action=stream&blobt ype=pdf&artid=371709

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Preferential neurotoxicity of colchicine for granule cells of the dentate gyrus of the adult rat. by Goldschmidt RB, Steward O.; 1980 May; http://www.pubmedcentral.gov/picrender.fcgi?tool=pmcentrez&action=stream&blobt ype=pdf&artid=349544

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The Dissociation by Colchicine of Phagocytosis from Increased Oxygen Consumption in Human Leukocytes. by Malawista SE, Bodel PT.; 1967 May; http://www.pubmedcentral.gov/picrender.fcgi?tool=pmcentrez&action=stream&blobt ype=pdf&artid=297081

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Topical colchicine selection of keratinocytes transduced with the multidrug resistance gene (MDR1) can sustain and enhance transgene expression in vivo. by Pfutzner W, Terunuma A, Tock CL, Snead EK, Kolodka TM, Gottesman MM, Taichman L, Vogel JC.; 2002 Oct 1; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=130592

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Tubulin bound to colchicine forms polymers different from microtubules. by Andreu JM, Timasheff SN.; 1982 Nov; http://www.pubmedcentral.gov/picrender.fcgi?tool=pmcentrez&action=stream&blobt ype=pdf&artid=347211

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Tubulins from different higher plant species are immunologically nonidentical and bind colchicine differentially. by Morejohn LC, Bureau TE, Tocchi LP, Fosket DE.; 1984 Mar; http://www.pubmedcentral.gov/picrender.fcgi?tool=pmcentrez&action=stream&blobt ype=pdf&artid=344851

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

A controlled trial of colchicine in primary biliary cirrhosis. Trial design and preliminary report. Author(s): Warnes TW, Smith A, Lee FI, Haboubi NY, Johnson PJ, Hunt L. Source: Journal of Hepatology. 1987 August; 5(1): 1-7. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=3655305

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A double-blind randomized controlled trial of colchicine in patients with hepatitis B virus-related postnecrotic cirrhosis. Author(s): Wang YJ, Lee SD, Hsieh MC, Lin HC, Lee FY, Tsay SH, Tsai YT, Hu OY, King ML, Lo KJ. Source: Journal of Hepatology. 1994 November; 21(5): 872-7. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=7890905

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A double-blind trial of colchicine in Behcet's syndrome. Author(s): Yurdakul S, Mat C, Tuzun Y, Ozyazgan Y, Hamuryudan V, Uysal O, Senocak M, Yazici H. Source: Arthritis and Rheumatism. 2001 November; 44(11): 2686-92. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11710724

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A hypothesis concerning the role of endogenous colchicine-like factors in the etiology of Alzheimer's disease. Author(s): Gorenstein C. Source: Medical Hypotheses. 1987 August; 23(4): 371-4. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=2443819

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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 prospective trial of colchicine and methotrexate in the treatment of primary biliary cirrhosis. Author(s): Kaplan MM, Schmid C, Provenzale D, Sharma A, Dickstein G, McKusick A. Source: Gastroenterology. 1999 November; 117(5): 1173-80. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=10535881

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A randomized controlled trial of colchicine plus ursodiol versus methotrexate plus ursodiol in primary biliary cirrhosis: ten-year results. Author(s): Kaplan MM, Cheng S, Price LL, Bonis PA. Source: Hepatology (Baltimore, Md.). 2004 April; 39(4): 915-23. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=15057894

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A randomized controlled trial to evaluate the slow-acting symptom modifying effects of a regimen containing colchicine in a subset of patients with osteoarthritis of the knee. Author(s): Das SK, Mishra K, Ramakrishnan S, Srivastava R, Agarwal GG, Singh R, Sircar AR. Source: Osteoarthritis and Cartilage / Oars, Osteoarthritis Research Society. 2002 April; 10(4): 247-52. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11950246

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A randomized controlled trial to evaluate the slow-acting symptom-modifying effects of colchicine in osteoarthritis of the knee: a preliminary report. Author(s): Das SK, Ramakrishnan S, Mishra K, Srivastava R, Agarwal GG, Singh R, Sircar AR. Source: Arthritis and Rheumatism. 2002 June 15; 47(3): 280-4. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12115158

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Accidental colchicine overdose. A case report and literature review. Author(s): Maxwell MJ, Muthu P, Pritty PE. Source: Emergency Medicine Journal : Emj. 2002 May; 19(3): 265-7. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11971849

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Accumulation of microtubule-based motor protein in a patient with colchicine myopathy. Author(s): Shinde A, Nakano S, Abe M, Kohara N, Akiguchi I, Shibasaki H. Source: Neurology. 2000 November 14; 55(9): 1414-5. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11087798

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Acute fatal colchicine intoxication in a patient on continuous ambulatory peritoneal dialysis (CAPD). Possible role of clarithromycin administration. Author(s): Dogukan A, Oymak FS, Taskapan H, Guven M, Tokgoz B, Utas C. Source: Clinical Nephrology. 2001 February; 55(2): 181-2. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11269688

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Acute myopathy induced by colchicine in a cyclosporine treated heart transplant recipient: possible role of the multidrug resistance transporter. Author(s): Gruberg L, Har-Zahav Y, Agranat O, Freimark D. Source: Transplantation Proceedings. 1999 August; 31(5): 2157-8. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=10455999

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Acute onset of colchicine myoneuropathy in cardiac transplant recipients: case studies of three patients. Author(s): Rana SS, Giuliani MJ, Oddis CV, Lacomis D. Source: Clinical Neurology and Neurosurgery. 1997 December; 99(4): 266-70. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=9491303

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Aneugenic activity in human cultured lymphocytes. An overall study with colchicine using the micronucleus assay and fluorescence in situ hybridization techniques. Author(s): Ramirez MJ, Surralles J, Puerto S, Creus A, Marcos R. Source: Mutagenesis. 1997 November; 12(6): 405-10. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=9412992

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Anti-/pro-oxidant effects of phenolic compounds in cells: are colchicine metabolites chain-breaking antioxidants? Author(s): Modriansky M, Tyurina YY, Tyurin VA, Matsura T, Shvedova AA, Yalowich JC, Kagan VE. Source: Toxicology. 2002 August 1; 177(1): 105-17. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12126799

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Antiproliferative activity of colchicine analogues on MDR-positive and MDRnegative human cancer cell lines. Author(s): De Vincenzo R, Scambia G, Ferlini C, Distefano M, Filippini P, Riva A, Bombardelli E, Pocar D, Gelmi ML, Benedetti Panici P, Mancuso S. Source: Anti-Cancer Drug Design. 1998 January; 13(1): 19-33. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=9474240

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Application of LC-MS analysis to a colchicine fatality. Author(s): Jones GR, Singer PP, Bannach B. Source: Journal of Analytical Toxicology. 2002 September; 26(6): 365-9. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12220019

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ATP-Dependent colchicine transport by human erythrocyte glutathione conjugate transporter. Author(s): Awasthi S, Singhal SS, Pandya U, Gopal S, Zimniak P, Singh SV, Awasthi YC. Source: Toxicology and Applied Pharmacology. 1999 March 15; 155(3): 215-26. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=10079207

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Azoospermia in familial Mediterranean fever patients: the role of colchicine and amyloidosis. Author(s): Ben-Chetrit E, Backenroth R, Haimov-Kochman R, Pizov G. Source: Annals of the Rheumatic Diseases. 1998 April; 57(4): 259-60. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=9709191

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Behcet disease with genitourinary involvement treated with colchicine. Author(s): Vordermark JS 2nd, Hudson LD. Source: Urology. 1984 March; 23(3): 290-2. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=6702042

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Behcet's disease and treatment with colchicine. Author(s): Raynor A, Askari AD. Source: Journal of the American Academy of Dermatology. 1980 May; 2(5): 396-400. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=7381068

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Behcet's syndrome and treatment with colchicine. Author(s): Rogers RS 3rd. Source: Journal of the American Academy of Dermatology. 1981 April; 4(4): 483-6. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=7229155

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Behcet's syndrome treated with colchicine. Author(s): de Bois MH, Geelhoed-Duijvestijn PH, Westedt ML. Source: The Netherlands Journal of Medicine. 1991 April; 38(3-4): 175-6. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=1881506

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Behcet's syndrome: immune regulation, circulating immune complexes, neutrophil migration, and colchicine therapy. Author(s): Jorizzo JL, Hudson RD, Schmalstieg FC, Daniels JC, Apisarnthanarax P, Henry JC, Gonzalez EB, Ichikawa Y, Cavallo T. Source: Journal of the American Academy of Dermatology. 1984 February; 10(2 Pt 1): 205-14. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=6371066

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Beneficial effect of colchicine in a case of sclerosing cholangitis. Author(s): Leiser A, Kadish U. Source: The American Journal of the Medical Sciences. 1986 June; 291(6): 416-8. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=3717199

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Benefit of colchicine in the treatment of Schamberg's disease. Author(s): Geller M. Source: Annals of Allergy, Asthma & Immunology : Official Publication of the American College of Allergy, Asthma, & Immunology. 2000 September; 85(3): 246. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11030283

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Binding of colchicine and thiocolchicoside to human serum proteins and blood cells. Author(s): Sabouraud A, Chappey O, Dupin T, Scherrmann JM. Source: Int J Clin Pharmacol Ther. 1994 August; 32(8): 429-32. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=7981928

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Biological evaluation on different human cancer cell lines of novel colchicine analogs. Author(s): De Vincenzo R, Ferlini C, Distefano M, Gaggini C, Riva A, Bombardelli E, Morazzoni P, Danieli B, Capelli G, Mancuso S, Scambia G. Source: Oncology Research. 1999; 11(3): 145-52. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=10527074

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Bone marrow depression associated with acute colchicine toxicity in the presence of hepatic dysfunction. Author(s): Boruchow IB. Source: Cancer. 1966 April; 19(4): 541-3. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=5933578

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Breast-feeding during colchicine therapy for familial Mediterranean fever. Author(s): Milunsky JM. Source: The Journal of Pediatrics. 1991 July; 119(1 ( Pt 1)): 164. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=2066854

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Brief report: treatment of severe colchicine overdose with colchicine-specific Fab fragments. Author(s): Baud FJ, Sabouraud A, Vicaut E, Taboulet P, Lang J, Bismuth C, Rouzioux JM, Scherrmann JM. Source: The New England Journal of Medicine. 1995 March 9; 332(10): 642-5. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=7845428

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Bronchoalveolar carcinoma in a patient with recurrent familial Mediterranean attacks, fibrothorax, and treatment with colchicine. Author(s): Ariad S, Sandbank J, Lupu L. Source: Isr Med Assoc J. 1999 October; 1(2): 121-2. No Abstract Available. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=10731312

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Colchicine as an oral corticosteroid sparing agent for asthma. Author(s): Dewey A, Dean T, Bara A, Lasserson TJ, Walters EH. Source: Cochrane Database Syst Rev. 2003; (4): Cd003273. Review. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=14583964

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Colchicine down-regulates cytochrome P450 2B6, 2C8, 2C9, and 3A4 in human hepatocytes by affecting their glucocorticoid receptor-mediated regulation. Author(s): Dvorak Z, Modriansky M, Pichard-Garcia L, Balaguer P, Vilarem MJ, Ulrichova J, Maurel P, Pascussi JM. Source: Molecular Pharmacology. 2003 July; 64(1): 160-9. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12815172

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Colchicine effect in a colonic hyperplastic polyp. A lesion mimicking serrated adenoma. Author(s): Torbenson M, Montgomery EA, Iacobuzio-Donahue C, Yardley JH, Wu TT, Abraham SC. Source: Archives of Pathology & Laboratory Medicine. 2002 May; 126(5): 615-7. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11958673

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Colchicine for the prevention of postpericardiotomy syndrome. Author(s): Finkelstein Y, Shemesh J, Mahlab K, Abramov D, Bar-El Y, Sagie A, Sharoni E, Sahar G, Smolinsky AK, Schechter T, Vidne BA, Adler Y. Source: Herz. 2002 December; 27(8): 791-4. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12574898

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Colchicine in tear fluid of treated patients with familial Mediterranean fever. Author(s): Leibovitch I, Alster Y, Scherrmann JM, Azmon B, Barequet IS, Livneh A, O'Brien TP, Lazar M, Loewenstein A. Source: Cornea. 2003 April; 22(3): 191-3. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12658080

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Colchicine myoneuropathy in a renal transplant patient. Author(s): Dupont P, Hunt I, Goldberg L, Warrens A. Source: Transplant International : Official Journal of the European Society for Organ Transplantation. 2002 July; 15(7): 374-6. Epub 2002 June 20. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12122515

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Colchicine myopathy in a patient with familial Mediterranean fever and normal renal function. Author(s): Kissin EY, Corbo JC, Farraye FA, Merkel PA. Source: Arthritis and Rheumatism. 2003 August 15; 49(4): 614-6. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12910572

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Colchicine neuromyopathy: a report of six cases. Author(s): Altiparmak MR, Pamuk ON, Pamuk GE, Hamuryudan V, Ataman R, Serdengecti K. Source: Clin Exp Rheumatol. 2002 July-August; 20(4 Suppl 26): S13-6. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12371628

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Colchicine poisoning resulting from accidental ingestion of meadow saffron (Colchicum autumnale). Author(s): Sannohe S, Makino Y, Kita T, Kuroda N, Shinozuka T. Source: J Forensic Sci. 2002 November; 47(6): 1391-6. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12455670

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Colchicine treatment in children with familial Mediterranean fever. Author(s): Ozkaya N, Yalcinkaya F. Source: Clinical Rheumatology. 2003 October; 22(4-5): 314-7. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=14579163

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Colchicine: where to use, where not to use? Author(s): Karakus SS, Engin H. Source: The Annals of Pharmacotherapy. 2002 January; 36(1): 172-3. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11816251

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Colchicine-induced acute myopathy in a patient with concomitant use of simvastatin. Author(s): Hsu WC, Chen WH, Chang MT, Chiu HC. Source: Clinical Neuropharmacology. 2002 September-October; 25(5): 266-8. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12410059

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Colchicine-induced myopathy with myotonia in a patient with chronic renal failure. Author(s): Caglar K, Odabasi Z, Safali M, Yenicesu M, Vural A. Source: Clinical Neurology and Neurosurgery. 2003 September; 105(4): 274-6. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12954545

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Colchicine-induced myopathy with normal creatine phosphokinase level in a renal transplant patient. Author(s): Caglar K, Safali M, Yavuz I, Odabasi Z, Yenicesu M, Vural A. Source: Nephron. 2002 December; 92(4): 922-4. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12399640

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Colchicine-induced rhabdomyolysis. Author(s): Phanish MK, Krishnamurthy S, Bloodworth LL. Source: The American Journal of Medicine. 2003 February 1; 114(2): 166-7. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12586247

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Colchicine-induced rhabdomyolysis. Author(s): Boomershine KH. Source: The Annals of Pharmacotherapy. 2002 May; 36(5): 824-6. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11978160

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Colchicine-induced rhabdomyolysis: the whole is greater than the sum of its parts! Author(s): Vasudevan AR, Uthamalingam S, Kumar S, Tamarin F, Brensilver JM. Source: The American Journal of Medicine. 2003 August 15; 115(3): 249. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12935834

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Combined treatment with vitamin E and colchicine in the early stages of Peyronie's disease. Author(s): Prieto Castro RM, Leva Vallejo ME, Regueiro Lopez JC, Anglada Curado FJ, Alvarez Kindelan J, Requena Tapia MJ. Source: Bju International. 2003 April; 91(6): 522-4. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12656907

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Comparative effect of colchicine and colchiceine on cytotoxicity and CYP gene expression in primary human hepatocytes. Author(s): Dvorak Z, Ulrichova J, Pichard-Garcia L, Modriansky M, Maurel P. Source: Toxicology in Vitro : an International Journal Published in Association with Bibra. 2002 June; 16(3): 219-27. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12020594

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Corneal wound healing in a patient treated with colchicine for familial Mediterranean Fever (FMF). Author(s): Leibovitch I, Alster Y, Lazar M, Langevitz P, Livneh A, Loewenstein A. Source: Rheumatology (Oxford, England). 2003 August; 42(8): 1021-2. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12869680

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Dapsone and colchicine inhibit adhesion of neutrophilic granulocytes to epidermal sections. Author(s): Modschiedler K, Weller M, Worl P, von den Driesch P. Source: Archives of Dermatological Research. 2000 January; 292(1): 32-6. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=10664013

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Death following colchicine poisoning. Author(s): McIntyre IM, Ruszkiewicz AR, Crump K, Drummer OH. Source: J Forensic Sci. 1994 January; 39(1): 280-6. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=8113710

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Deaths associated with inappropriate intravenous colchicine administration. Author(s): Bonnel RA, Villalba ML, Karwoski CB, Beitz J. Source: The Journal of Emergency Medicine. 2002 May; 22(4): 385-7. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12113850

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Delay of corneal wound healing in patients treated with colchicine. Author(s): Alster Y, Varssano D, Loewenstein A, Lazar M. Source: Ophthalmology. 1997 January; 104(1): 118-9. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=9022114

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Delayed pressure urticaria, objective evaluation of a variable disease using a dermographometer and assessment of treatment using colchicine. Author(s): Lawlor F, Black AK, Ward AM, Morris R, Greaves MW. Source: The British Journal of Dermatology. 1989 March; 120(3): 403-8. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=2653402

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Demonstration of efficacy of combining corticosteroids and colchicine in two patients with idiopathic sclerosing mesenteritis. Author(s): Genereau T, Bellin MF, Wechsler B, Le TH, Bellanger J, Grellet J, Godeau P. Source: Digestive Diseases and Sciences. 1996 April; 41(4): 684-8. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=8674388

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Derivatives of colchicine preferentially taken up by the liver: an approach to the treatment of liver fibrosis. Author(s): Palmerini CA, Floridi A, Arienti G. Source: Biotechnology and Applied Biochemistry. 1995 August; 22 ( Pt 1): 15-22. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=7576253

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Detection of chromosome 2 and chromosome 7 within X-ray- or colchicine-induced micronuclei by fluorescence in situ hybridization. Author(s): Wuttke K, Streffer C, Muller WU. Source: Mutagenesis. 1997 March; 12(2): 55-9. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=9106244

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Determination of the antimitotic agents N-desacetylcolchicine, demecolcine and colchicine in serum and urine. Author(s): Ko RJ, Li WY, Koda RT. Source: Journal of Chromatography. 1990 February 23; 525(2): 411-8. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=2329167

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Detrusor instability following colchicine therapy. Author(s): Evans JW, Christmas TJ. Source: British Journal of Urology. 1991 May; 67(5): 552-4. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=2039931

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Differences in signal transduction between Fc gamma receptors (Fc gamma RII, Fc gamma RIII) and FMLP receptors in neutrophils. Effects of colchicine on pertussis toxin sensitivity and diacylglycerol formation. Author(s): Reibman J, Haines KA, Gude D, Weissmann G. Source: Journal of Immunology (Baltimore, Md. : 1950). 1991 February 1; 146(3): 988-96. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=1846387

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Disappearance of cryoglobulinemia with improvement in other immune parameters in a case of primary biliary cirrhosis treated with colchicine. Author(s): Delpre G, Shohat B, Kadish U, Pick A, Joshua H. Source: Gastroenterologie Clinique Et Biologique. 1990; 14(2): 182-3. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=2133039

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Discovery of a novel compound: insight into mechanisms for acrylamide-induced axonopathy and colchicine-induced apoptotic neuronal cell death. Author(s): J Rheumatol. 2001 Sep;28(9):2144 Source: Brain Research. 2001 August 3; 909(1-2): 8-19. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11824425

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Dissociation of the inhibitory effect of dapsone on the generation of oxygen intermediates--in comparison with that of colchicine and various scavengers. Author(s): Niwa Y, Sakane T, Miyachi Y. Source: Biochemical Pharmacology. 1984 August 1; 33(15): 2355-60. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=6087824

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Does colchicine also induce a clearance of the established amyloid deposits? Author(s): Tuglular S, Bihorac A, Ozener IC, Akoglu E. Source: Nephrology, Dialysis, Transplantation : Official Publication of the European Dialysis and Transplant Association - European Renal Association. 1999 April; 14(4): 1042-3. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=10328512

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Does colchicine work? The results of the first controlled study in acute gout. Author(s): Ahern MJ, Reid C, Gordon TP, McCredie M, Brooks PM, Jones M. Source: Aust N Z J Med. 1987 June; 17(3): 301-4. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=3314832

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Does the lack of the P-glycoprotein efflux pump in neutrophils explain the efficacy of colchicine in familial Mediterranean fever and other inflammatory diseases? Author(s): Ben-Chetrit E, Levy M. Source: Medical Hypotheses. 1998 November; 51(5): 377-80. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=9848464

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Double minute chromosomes carrying the human multidrug resistance 1 and 2 genes are generated from the dimerization of submicroscopic circular DNAs in colchicineselected KB carcinoma cells. Author(s): Schoenlein PV, Shen DW, Barrett JT, Pastan I, Gottesman MM. Source: Molecular Biology of the Cell. 1992 May; 3(5): 507-20. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=1611154

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Double-masked trial of cyclosporin versus colchicine and long-term open study of cyclosporin in Behcet's disease. Author(s): Masuda K, Nakajima A, Urayama A, Nakae K, Kogure M, Inaba G. Source: Lancet. 1989 May 20; 1(8647): 1093-6. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=2566048

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Effect of colchicine and cytokines on MEFV expression and C5a inhibitor activity in human primary fibroblast cultures. Author(s): Abedat S, Urieli-Shoval S, Shapira E, Calko S, Ben-Chetrit E, Matzner Y. Source: Isr Med Assoc J. 2002 January; 4(1): 7-12. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11802319

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Effect of colchicine and its derivatives on the expression of selected isoforms of cytochrome P450 in primary cultures of human hepatocytes. Author(s): Dvorak Z, Ulrichova J, Modriansky M, Maurel P. Source: Acta Univ Palacki Olomuc Fac Med. 2000; 143: 47-50. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11144118

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Effect of colchicine in the subcorneal pustular dermatosis type of IgA pemphigus. Author(s): Hodak E, Lapidoth M, David M. Source: Journal of the American Academy of Dermatology. 1999 January; 40(1): 91-4. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=9922018

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Effect of colchicine on the activity of cathepsin B and D in human liver cirrhosis. Author(s): Stancikova M, Frysak Z, Trnavsky K. Source: Acta Med Hung. 1987; 44(2-3): 181-8. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=3684446

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Effect of cytochalasin B on the induction of chromosome missegregation by colchicine at low concentrations in human lymphocytes. Author(s): Minissi S, Gustavino B, Degrassi F, Tanzarella C, Rizzoni M. Source: Mutagenesis. 1999 January; 14(1): 43-9. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=10474820

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Effects of additional administration of colchicine in ursodeoxycholic acid-treated patients with primary biliary cirrhosis: a prospective randomized study. Author(s): Ikeda T, Tozuka S, Noguchi O, Kobayashi F, Sakamoto S, Marumo F, Sato C. Source: Journal of Hepatology. 1996 January; 24(1): 88-94. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=8834030

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Effects of colchicine on inflammatory cytokines and selectins in familial Mediterranean fever. Author(s): Kiraz S, Ertenli I, Arici M, Calguneri M, Haznedaroglu I, Celik I, Pay S, Kirazli S. Source: Clin Exp Rheumatol. 1998 November-December; 16(6): 721-4. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=9844766

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Effects of TNF-alpha/colchicine combined treatment on Burkitt lymphoma cells: molecular and ultrastructural changes. Author(s): Di Pietro R, Robuffo I, Pucci AM, Bosco D, Santavenere E. Source: Cytokine. 1999 February; 11(2): 144-50. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=10089136

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Effects of vinblastine, colchicine, and verapamil on rhodamine 123 accumulation in human P-glycoprotein-positive leukemia cells. Author(s): Lautier D, Canitrot Y, Salmon JM. Source: Anticancer Res. 1994 November-December; 14(6B): 2589-95. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=7872686

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Efficacy and safety assessment of 0.5% and 1% colchicine cream in the treatment of actinic keratoses. Author(s): Akar A, Bulent Tastan H, Erbil H, Arca E, Kurumlu Z, Gur AR. Source: The Journal of Dermatological Treatment. 2001 December; 12(4): 199-203. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12241628

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Efficacy of colchicine alone or in combination with vinca alkaloids in severe corticoid-resistant thrombocytopenic purpura: six cases. Author(s): Bonnotte B, Gresset AC, Chvetzoff G, Martin F, Lorcerie B, Chauffert B. Source: The American Journal of Medicine. 1999 December; 107(6): 645-6. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=10625040

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Efficacy of colchicine in familial Mediterranean fever is well established. Author(s): Drenth JP. Source: Bmj (Clinical Research Ed.). 1996 July 27; 313(7051): 233. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=8696225

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Efficacy of colchicine in patients with primary biliary cirrhosis poorly responsive to ursodiol and methotrexate. Author(s): Lee YM, Kaplan MM. Source: The American Journal of Gastroenterology. 2003 January; 98(1): 205-8. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12526960

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Efficacy of colchicine therapy in amyloid nephropathy of familial Mediterranean fever. Author(s): Oner A, Erdogan O, Demircin G, Bulbul M, Memis L. Source: Pediatric Nephrology (Berlin, Germany). 2003 June; 18(6): 521-6. Epub 2003 April 16. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12698329

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Efficiency of colchicine and corticosteroids in a leg ulceration with cholesterol embolism in a woman with rheumatoid arthritis. Author(s): Verneuil L, Ze Bekolo R, Dompmartin A, Comoz F, Marcelli C, Leroy D. Source: Rheumatology (Oxford, England). 2003 August; 42(8): 1014-6. Review. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12869676

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Epithelial cell mitotic arrest--a useful postmortem histologic marker in cases of possible colchicine toxicity. Author(s): Gilbert JD, Byard RW. Source: Forensic Science International. 2002 April 18; 126(2): 150-2. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12084492

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Evaluation of 11C-colchicine for PET imaging of multiple drug resistance. Author(s): Levchenko A, Mehta BM, Lee JB, Humm JL, Augensen F, Squire O, Kothari PJ, Finn RD, Leonard EF, Larson SM. Source: Journal of Nuclear Medicine : Official Publication, Society of Nuclear Medicine. 2000 March; 41(3): 493-501. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=10716325

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Evaluation of therapy for cast nephropathy: failure of colchicine to alter urinary Tamm Horsfall glycoprotein excretion in normal subjects. Author(s): Cairns HS, Dawnay A, Woolfson RG, Unwin RJ. Source: Experimental Nephrology. 1994 July-August; 2(4): 257-8. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=8069661

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Expression of a full-length cDNA for the human "MDR1" gene confers resistance to colchicine, doxorubicin, and vinblastine. Author(s): Ueda K, Cardarelli C, Gottesman MM, Pastan I. Source: Proceedings of the National Academy of Sciences of the United States of America. 1987 May; 84(9): 3004-8. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=3472246

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Extended delivery of the antimitotic agent colchicine from thermoresponsive Nisopropylacrylamide-based copolymer films to human vascular smooth muscle cells. Author(s): Wilson SJ, Gorelov AV, Rochev YA, McGillicuddy F, Dawson KA, Gallagher WM, Keenan AK. Source: Journal of Biomedical Materials Research. 2003 November 1; 67A(2): 667-73. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=14566811

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Failure of colchicine for palmo-plantar pustulosis. Author(s): English JS, Fenton DA, Wilkinson JD. Source: Clinical and Experimental Dermatology. 1983 March; 8(2): 207-8. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=6342878

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Failure of colchicine for palmo-plantar pustulosis. Author(s): Mann RJ. Source: The British Journal of Dermatology. 1982 March; 106(3): 373. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=7039659

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Failure of colchicine in the treatment of Mollaret's meningitis. Author(s): Stamm AM, Livingston WK, Cobbs CG, Dismukes WE. Source: Archives of Internal Medicine. 1984 November; 144(11): 2265-6. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=6497532

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Failure of colchicine in the treatment of severe acne vulgaris. Author(s): Schepis C, Siragusa M, Palazzo R, Guerra AP. Source: Acta Dermato-Venereologica. 1999 November; 79(6): 491. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=10598778

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Failure of colchicine to improve short-term survival in patients with alcoholic hepatitis. Author(s): Akriviadis EA, Steindel H, Pinto PC, Fong TL, Kanel G, Reynolds TB, Gupta S. Source: Gastroenterology. 1990 September; 99(3): 811-8. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=2199290

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Failure of colchicine to reduce inhaled triamcinolone dose in patients with asthma. Author(s): Newman KB, Mason UG, Buchmeier A, Schmaling KB, Corsello P, Nelson HS. Source: The Journal of Allergy and Clinical Immunology. 1997 February; 99(2): 176-8. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=9042041

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Familial Mediterranean fever associated with menstruation. Efficacy of intermittent colchicine therapy. Author(s): Milano AM. Source: The American Journal of Gastroenterology. 1981 October; 76(4): 363-4. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=7198867

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Familial Mediterranean fever in the colchicine era: the fate of one family. Author(s): Zemer D, Livneh A, Pras M, Sohar E. Source: American Journal of Medical Genetics. 1993 February 1; 45(3): 340-4. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=8434621

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Fatal cardiovascular collapse following acute colchicine ingestion. Author(s): Horton R. Lancet. 2000 Oct 14;356(9238):1292 Source: Journal of Toxicology. Clinical Toxicology. 2000; 38(1): 51-4. Review. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11073015

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Fatal colchicine overdose. Author(s): Garden AL, Judson JA. Source: N Z Med J. 1990 August 22; 103(896): 402. No Abstract Available. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=2385420

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Fatal colchicine overdose: report of a case and review of the literature. Author(s): Milne ST, Meek PD. Source: The American Journal of Emergency Medicine. 1998 October; 16(6): 603-8. Review. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=9786547

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Fatal colchicine toxicity. Author(s): Kubler PA. Source: The Medical Journal of Australia. 2000 May 15; 172(10): 498-9. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=10901774

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Fatal colchicine toxicity. Author(s): Simons RJ, Kingma DW. Source: The American Journal of Medicine. 1989 March; 86(3): 356-7. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=2919622

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Fatal colchicine toxicity: report of a case. Author(s): Stanley MW, Taurog JD, Snover DC. Source: Clin Exp Rheumatol. 1984 April-June; 2(2): 167-71. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=6532621

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Fatal i.v. colchicine injection in a 60-year-old woman. Author(s): Luciani I. Source: Journal of Emergency Nursing: Jen : Official Publication of the Emergency Department Nurses Association. 1989 March-April; 15(2( Pt 1)): 80-2. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=2649722

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Fc receptors on human T lymphocytes. V: Effects of colchicine and cytochalasin B on Fc receptor expression. Author(s): Reaman GH, Poplack DG, Broder S, Pichler WJ. Source: Journal of Immunology (Baltimore, Md. : 1950). 1980 November; 125(5): 2215-9. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=7000898

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Fertility and obstetric history in patients with familial Mediterranean fever on longterm colchicine therapy. Author(s): Ehrenfeld M, Brzezinski A, Levy M, Eliakim M. Source: British Journal of Obstetrics and Gynaecology. 1987 December; 94(12): 1186-91. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=3426990

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Fever of undetermined origin as the presenting symptom of Behcet's disease: a favorable response to colchicine. Author(s): Pines A, Kaplinsky N, Olchovsky D, Bregman J, Frankl O. Source: Southern Medical Journal. 1984 June; 77(6): 802-3. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=6729567

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Fixed drug eruption due to colchicine. Author(s): Mochida K, Teramae H, Hamada T. Source: Dermatology (Basel, Switzerland). 1996; 192(1): 61. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=8832955

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Frequent doses of intravenous colchicine can be lethal. Author(s): Freeman DL. Source: The New England Journal of Medicine. 1983 August 4; 309(5): 310. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=6866055

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Gastrointestinal effects of long-term colchicine therapy in patients with recurrent polyserositis (familial mediterranean fever). Author(s): Ehrenfeld M, Levy M, Sharon P, Rachmilewitz D, Eliakim M. Source: Digestive Diseases and Sciences. 1982 August; 27(8): 723-7. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=6284460

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Gastrointestinal, hepatorenal, and neuromuscular toxicity caused by cyclosporinecolchicine interaction in renal transplantation. Author(s): Yussim A, Bar-Nathan N, Lustig S, Shaharabani E, Geier E, Shmuely D, Nakache R, Shapira Z. Source: Transplantation Proceedings. 1994 October; 26(5): 2825-6. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=7940890

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Granulocyte-colony stimulating factor in the treatment of colchicine poisoning. Author(s): Critchley JA, Critchley LA, Yeung EA, Young RP, Young RJ, Chan TY, Goh VK. Source: Human & Experimental Toxicology. 1997 April; 16(4): 229-32. Review. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=9154449

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Granulocytopenia complicating colchicine therapy for primary biliary cirrhosis. Author(s): Finklestein M, Goldman L, Grace ND, Foley M, Randall N. Source: Gastroenterology. 1987 December; 93(6): 1231-5. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=3678740

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Growth and IGF-1 levels of children with familial Mediterranean fever on colchicine treatment. Author(s): Savgan-Gurol E, Kasapcopur O, Hatemi S, Ercan O, Caliskan S, Sever L, Ozdogan H, Arisoy N. Source: Clin Exp Rheumatol. 2001 September-October; 19(5 Suppl 24): S72-5. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11760406

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Growth hormone promotion of tubulin polymerization stabilizes the microtubule network and protects against colchicine-induced apoptosis. Author(s): Goh EL, Pircher TJ, Lobie PE. Source: Endocrinology. 1998 October; 139(10): 4364-72. Erratum In: Endocrinology 1998 November 139(11): 5. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=9751520

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Haemodynamic studies in eight cases of acute colchicine poisoning. Author(s): Sauder P, Kopferschmitt J, Jaeger A, Mantz JM. Source: Hum Toxicol. 1983 April; 2(2): 169-73. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=6862460

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High-performance liquid chromatography coupled to ion spray mass spectrometry for the determination of colchicine at ppb levels in human biofluids. Author(s): Tracqui A, Kintz P, Ludes B, Rouge C, Douibi H, Mangin P. Source: Journal of Chromatography. B, Biomedical Applications. 1996 January 26; 675(2): 235-42. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=8852710

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Histamine release from human leukocytes: studies with deuterium oxide, colchicine, and cytochalasin B. Author(s): Gillespie E, Lichtenstein LM. Source: The Journal of Clinical Investigation. 1972 November; 51(11): 2941-7. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=4117007

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Human polymorphonuclear leukocytes: demonstration of microtubules and effect of colchicine. Author(s): Malawista SE, Bensch KG. Source: Science. 1967 April 28; 156(774): 521-2. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=6021678

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Human skin anaphylaxis. Effect of cyclic AMP on the two stages of allergic histamine release from human skin, and colchicine-induced inhibition of cutaneous allergic histamine release. Author(s): Yamamoto S, Ozasa S, Marda M. Source: Hiroshima J Med Sci. 1977 September; 26(2-3): 167-71. No Abstract Available. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=73532

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Hyper-IGD syndrome: a new case treated with colchicine. Author(s): Ostuni PA, Lazzarin P, Ongaro G, Gusi R, Todesco S, Gambari PF. Source: Clinical Rheumatology. 1988 September; 7(3): 398-401. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=3229086

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Hypernatraemia and polyuria due to high-dose colchicine in a suicidal patient. Author(s): Usalan C, Altun B, Ulusoy S, Erdem Y, Yasavul U, Turgan C, Caglar S. Source: Nephrology, Dialysis, Transplantation : Official Publication of the European Dialysis and Transplant Association - European Renal Association. 1999 June; 14(6): 1556-7. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=10383025

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Hyperthyroidism due to iodide contained in a colchicine preparation. Author(s): Rousseau L, Lamarque P, Rapelanoro R, Malvy D, Fach J, Longy-Boursier M, Le Bras M. Source: Rev Rhum Engl Ed. 1997 June; 64(6): 434-5. No Abstract Available. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=9513623

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Idiopathic pulmonary fibrosis: Impact of oxygen and colchicine, prednisone, or no therapy on survival. Author(s): Douglas WW, Ryu JH, Schroeder DR. Source: American Journal of Respiratory and Critical Care Medicine. 2000 April; 161(4 Pt 1): 1172-8. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=10764308

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Impaired renal function and colchicine toxicity. Author(s): Boers M. Source: The Journal of Rheumatology. 1991 December; 18(12): 1942-3. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=1819267

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In vitro effects of colchicine on human erythrocyte membranes: an ESR study. Author(s): Korkmaz O, Korkmaz M, Aksoz E. Source: Z Naturforsch [c]. 1997 July-August; 52(7-8): 522-9. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=9309881

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In vivo uptake of carbon-14-colchicine for identification of tumor multidrug resistance. Author(s): Mehta BM, Rosa E, Biedler JL, Larson SM. Source: Journal of Nuclear Medicine : Official Publication, Society of Nuclear Medicine. 1994 July; 35(7): 1179-84. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=8014680

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Induction of apoptotic cell death in differentiating neuroblastoma SH-SY5Y cells by colchicine. Author(s): Nakagawa-Yagi Y. Source: Biochemical and Biophysical Research Communications. 1994 March 15; 199(2): 807-17. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=8135827

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Ineffectiveness of colchicine for the prevention of restenosis after coronary angioplasty. Author(s): O'Keefe JH Jr, McCallister BD, Bateman TM, Kuhnlein DL, Ligon RW, Hartzler GO. Source: Journal of the American College of Cardiology. 1992 June; 19(7): 1597-600. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=1593057

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Inhibition of mitogen-induced changes in intracellular fluorescein fluorescence polarization of human peripheral blood lymphocytes by colchicine, vinblastine and cytochalasin B. Author(s): Eisenthal A, Marder O, Lifschitz-Mercer B, Skornick Y, Tirosh R, Weinreb A, Deutsch M. Source: Cell Structure and Function. 1996 June; 21(3): 159-66. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=8853552

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Inhibition of tubulin polymerization by vitilevuamide, a bicyclic marine peptide, at a site distinct from colchicine, the vinca alkaloids, and dolastatin 10. Author(s): Edler MC, Fernandez AM, Lassota P, Ireland CM, Barrows LR. Source: Biochemical Pharmacology. 2002 February 15; 63(4): 707-15. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11992639

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Interactions of colchicine with tubulin. Author(s): Hastie SB. Source: Pharmacology & Therapeutics. 1991; 51(3): 377-401. Review. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=1792241

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Interest of colchicine for the treatment of cystic fibrosis patients. Preliminary report. Author(s): Sermet-Gaudelus I, Stoven V, Annereau JP, Witko-Sarsat V, Reinert P, Guyot M, Descamps-Latscha B, Lallemand JY, Lenoir G. Source: Mediators of Inflammation. 1999; 8(1): 13-5. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=10704084

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Interferon alfa-2b, colchicine, and benzathine penicillin versus colchicine and benzathine penicillin in Behcet's disease: a randomised trial. Author(s): Demiroglu H, Ozcebe OI, Barista I, Dundar S, Eldem B. Source: Lancet. 2000 February 19; 355(9204): 605-9. Retraction In: http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=10696980

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Interindividual variation in cytogenetic response to X-ray and colchicine measured with the cytokinesis-block micronucleus assay. Author(s): Odagiri Y, Uchida H, Shibazaki S. Source: Mutation Research. 1997 November 19; 381(1): 1-13. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=9403025

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Intravenous colchicine for low-back pain: a double-blind study. Author(s): Simmons JW, Harris WP, Koulisis CW, Kimmich SJ. Source: Spine. 1990 July; 15(7): 716-7. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=2145645

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Intravenous colchicine for treatment of patients with familial Mediterranean fever unresponsive to oral colchicine. Author(s): Lidar M, Kedem R, Langevitz P, Pras M, Livneh A. Source: The Journal of Rheumatology. 2003 December; 30(12): 2620-3. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=14719203

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Intravenous colchicine use in crystal-induced arthropathies: a retrospective analysis of hospitalized patients. Author(s): Maldonado MA, Salzman A, Varga J. Source: Clin Exp Rheumatol. 1997 September-October; 15(5): 487-92. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=9307855

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Involvement of microtubule integrity in memory impairment caused by colchicine. Author(s): Nakayama T, Sawada T. Source: Pharmacology, Biochemistry, and Behavior. 2002 January-February; 71(1-2): 11938. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11812515

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Is colchicine effective in Peyronie's disease? A pilot study. Author(s): Akkus E, Carrier S, Rehman J, Breza J, Kadioglu A, Lue TF. Source: Urology. 1994 August; 44(2): 291-5. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=8048212

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Is myopathy in renal transplant patients induced by cyclosporin or colchicine? Author(s): Rumpf KW, Henning HV. Source: Lancet. 1990 March 31; 335(8692): 800-1. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=1969550

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Killing and characterizing action of colchicine in vitro on lymphocytes of chronic lymphocytic leukaemia. Author(s): Thomson AE, O'Connor TW, Wetherley-Mein G. Source: Scand J Haematol. 1972; 9(3): 231-47. No Abstract Available. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=5055033

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Kinetics of colchicine inhibition of mitogenesis in individual lymphocytes. Author(s): Gunther GR, Wang JL, Edelman GM. Source: Experimental Cell Research. 1976 March 1; 98(1): 15-22. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=1253835

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Lack of effect of colchicine in alcoholic cirrhosis: final results of a double blind randomized trial. Author(s): Cortez-Pinto H, Alexandrino P, Camilo ME, Gouveia-Oliveira A, Santos PM, Alves MM, Moura MC. Source: European Journal of Gastroenterology & Hepatology. 2002 April; 14(4): 377-81. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11943949

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Lack of effect of colchicine on human neutrophil chemotaxis under agarose. Author(s): Daughaday CC, Bohrer AN, Spilberg I. Source: Experientia. 1981 February 15; 37(2): 199-200. No Abstract Available. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=7238758

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Lactic acidosis, prostaglandin E1, and colchicine. Author(s): Horrobin DF, Manku MS. Source: British Medical Journal. 1978 March 11; 1(6113): 651. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=630276

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Late diagnosis of severe colchicine intoxication. Author(s): Guven AG, Bahat E, Akman S, Artan R, Erol M. Source: Pediatrics. 2002 May; 109(5): 971-3. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11986465

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Late occurrence of chronic renal failure in familial mediterranean fever after 20 years of colchicine treatment. Author(s): Vigneau C, Petrover D, Sraer JD. Source: Annals of Internal Medicine. 2001 December 18; 135(12): 1096. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11747405

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Leukosialin (CD43, sialophorin) redistribution in uropods of polarized neutrophils is induced by CD43 cross-linking by antibodies, by colchicine or by chemotactic peptides. Author(s): Seveau S, Lopez S, Lesavre P, Guichard J, Cramer EM, Halbwachs-Mecarelli L. Source: Journal of Cell Science. 1997 July; 110 ( Pt 13): 1465-75. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=9224764

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Linear IgA bullous dermatosis. Successful treatment with colchicine. Author(s): Aram H. Source: Archives of Dermatology. 1984 July; 120(7): 960-1. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=6375580

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Localization and expression of Jun-like immunoreactivity in apoptotic neurons induced by colchicine administration in vivo and in vitro depends on the antisera used. Author(s): Pozas E, Aguado F, Ferrer I. Source: Acta Neuropathologica. 1999 August; 98(2): 119-28. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=10442550

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Localized Castleman's disease and nephrotic syndrome not responsive to resection plus colchicine therapy. Author(s): Derici U, Arinsoy T, Ataoglu O, Bali M, Eroglu A, Goker B, Sindel S. Source: Annals of Hematology. 2002 July; 81(7): 399-401. Epub 2002 June 25. Review. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12185513

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Localized linear IgA disease responding to colchicine. Author(s): Benbenisty KM, Bowman PH, Davis LS. Source: International Journal of Dermatology. 2002 January; 41(1): 56-8. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11895519

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Long-term colchicine for recalcitrant palmoplantar pustulosis: treatment outcome in 3 patients. Author(s): Wong SS, Tan KC, Goh CL. Source: Cutis; Cutaneous Medicine for the Practitioner. 2001 September; 68(3): 216-8. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11579788

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Long-term colchicine prophylaxis in children with familial Mediterranean fever (recurrent hereditary polyserositis). Author(s): Majeed HA, Carroll JE, Khuffash FA, Hijazi Z. Source: The Journal of Pediatrics. 1990 June; 116(6): 997-9. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=2112191

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Long-term colchicine prophylaxis in familial Mediterranean fever. Author(s): Levy M, Eliakim M. Source: British Medical Journal. 1977 September 24; 2(6090): 808. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=912334

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Long-term colchicine therapy for renal amyloidosis in familial Mediterranean fever. Author(s): Walker F, Bear RA. Source: Can Med Assoc J. 1982 December 15; 127(12): 1163-4. No Abstract Available. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=7139463

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Long-term colchicine treatment in children with familial Mediterranean fever. Author(s): Zemer D, Livneh A, Danon YL, Pras M, Sohar E. Source: Arthritis and Rheumatism. 1991 August; 34(8): 973-7. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=1859491

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Long-term effects of cyclophosphamide and colchicine treatment in Behcet's disease. Author(s): Kazokoglu H, Saatci O, Cuhadaroglu H, Eldem B. Source: Ann Ophthalmol. 1991 April; 23(4): 148-51. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=2064258

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Long-term evaluation of colchicine in the treatment of scleroderma. Author(s): Alarcon-Segovia D, Ramos-Niembro F, Ibanez de Kasep G, Alcocer J, Tamayo RP. Source: The Journal of Rheumatology. 1979 November-December; 6(6): 705-12. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=529256

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Long-term follow-up of patients with primary biliary cirrhosis on colchicine therapy. Author(s): Zifroni A, Schaffner F. Source: Hepatology (Baltimore, Md.). 1991 December; 14(6): 990-3. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=1959887

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Long-term suppression of chronic Sweet's syndrome with colchicine. Author(s): Ritter S, George R, Serwatka LM, Elston DM. Source: Journal of the American Academy of Dermatology. 2002 August; 47(2): 323-4. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12140489

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Low-dose colchicine inhibits astrocyte, fibroblast, and retinal pigment epithelial cell migration and proliferation. Author(s): Lemor M, de Bustros S, Glaser BM. Source: Archives of Ophthalmology. 1986 August; 104(8): 1223-5. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=3741255

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Markedly altered colchicine kinetics in a fatal intoxication: examination of contributing factors. Author(s): Borron SW, Scherrmann JM, Baud FJ. Source: Human & Experimental Toxicology. 1996 November; 15(11): 885-90. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=8938483

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Marrow aplasia following colchicine treatment for gouty arthritis. Author(s): Ferrannini E, Pentimone F. Source: Clin Exp Rheumatol. 1984 April-June; 2(2): 173-5. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=6532622

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Massive overdose of colchicine. Author(s): Davies HO, Hyland RH, Morgan CD, Laroye GJ. Source: Cmaj : Canadian Medical Association Journal = Journal De L'association Medicale Canadienne. 1988 February 15; 138(4): 335-6. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=3338005

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May colchicine therapy be of value in the prevention of dialysis amyloidosis? Author(s): Arik N, Yuksel H, Adam B, Akpolat T, Ozdemir O. Source: Nephron. 1996; 73(2): 365-6. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=8773394

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Mechanism of action of colchicine. VI: Effect of colchicine on generation of leukotriene B4 by human polymorphonuclear leukocytes. Author(s): Ouyang Y, Wang W, Bhuta S, Chang YH. Source: Clin Exp Rheumatol. 1989 July-August; 7(4): 397-402. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=2574088

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Mechanism of action of E7010, an orally active sulfonamide antitumor agent: inhibition of mitosis by binding to the colchicine site of tubulin. Author(s): Yoshimatsu K, Yamaguchi A, Yoshino H, Koyanagi N, Kitoh K. Source: Cancer Research. 1997 August 1; 57(15): 3208-13. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=9242451

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Mechanisms of colchicine effect in the treatment of asbestosis and idiopathic pulmonary fibrosis. Author(s): Addrizzo-Harris DJ, Harkin TJ, Tchou-Wong KM, McGuinness G, Goldring R, Cheng D, Rom DW. Source: Lung. 2002; 180(2): 61-72. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12172901

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Metabolic and morphologic effects of colchicine on human T-lymphocyte expression of Fc mu and Fc gamma receptors. Author(s): Ercolani L, Schulte WE. Source: Cellular Immunology. 1983 April 15; 77(2): 222-32. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=6303602

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Microtubules and lymphocyte responses: effect of colchicine and taxol on mitogeninduced human lymphocyte activation and proliferation. Author(s): Cuthbert JA, Shay JW. Source: Journal of Cellular Physiology. 1983 August; 116(2): 127-34. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=6134740

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Miscellaneous treatments: thalidomide, potassium iodide, levamisole, clofazimine, colchicine, and D-penicillamine. Author(s): Sanchez MR. Source: Clinics in Dermatology. 2000 January-February; 18(1): 131-45. Review. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=10701095

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Mitochondria in living cells cultured from human chorionic villi: the effects of colchicine on numbers and distribution. Author(s): Addai FK, Ockleford CD. Source: Journal of Anatomy. 1986 August; 147: 219-33. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=3319997

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Model-independent pharmacokinetics of colchicine after oral administration to healthy volunteers. Author(s): Girre C, Thomas G, Scherrmann JM, Crouzette J, Fournier PE. Source: Fundamental & Clinical Pharmacology. 1989; 3(5): 537-43. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=2606428

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Modulation of platelet-derived growth factor B mRNA abundance in macrophages by colchicine and dibutyryl-cAMP. Author(s): Wangoo A, Haynes AR, Sutcliffe SP, Sorooshian M, Shaw RJ. Source: Molecular Pharmacology. 1992 October; 42(4): 584-9. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=1331750

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Molecular basis of preferential resistance to colchicine in multidrug-resistant human cells conferred by Gly-185----Val-185 substitution in P-glycoprotein. Author(s): Safa AR, Stern RK, Choi K, Agresti M, Tamai I, Mehta ND, Roninson IB. Source: Proceedings of the National Academy of Sciences of the United States of America. 1990 September; 87(18): 7225-9. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=1976255

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Muckle-Wells syndrome nephropathy: lack of response to colchicine therapy. Author(s): Bustorff MM, Oliveria JP, Moura C, Carvalho E, Faria V, Guerra L. Source: Nephrology, Dialysis, Transplantation : Official Publication of the European Dialysis and Transplant Association - European Renal Association. 1995; 10(5): 709-10. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=7566591

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Multicentre randomized placebo-controlled trial of ursodeoxycholic acid with or without colchicine in symptomatic primary biliary cirrhosis. Author(s): Almasio PL, Floreani A, Chiaramonte M, Provenzano G, Battezzati P, Crosignani A, Podda M, Todros L, Rosina F, Saccoccio G, Manenti F, Ballardini G, Bianchi FP, Scheuer PJ, Davies SE, Craxi A. Source: Alimentary Pharmacology & Therapeutics. 2000 December; 14(12): 1645-52. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11121914

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Multiple organ failure in a kidney transplant patient receiving both colchicine and cyclosporine. Author(s): Minetti EE, Minetti L. Source: Journal of Nephrology. 2003 May-June; 16(3): 421-5. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12832745

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Muscle weakness due to colchicine in a renal transplant recipient. Author(s): Jagose JT, Bailey RR. Source: N Z Med J. 1997 September 12; 110(1051): 343. No Abstract Available. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=9323377

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Myotonia in colchicine myoneuropathy. Author(s): Rutkove SB, De Girolami U, Preston DC, Freeman R, Nardin RA, Gouras GK, Johns DR, Raynor EM. Source: Muscle & Nerve. 1996 July; 19(7): 870-5. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=8965841

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Nasal response to capsaicin in patients with allergic rhinitis and in healthy volunteers: effect of colchicine. Author(s): Roche N, Lurie A, Authier S, Dusser DJ. Source: American Journal of Respiratory and Critical Care Medicine. 1995 April; 151(4): 1151-8. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=7697245

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Neurotoxicity of colchicine and other tubulin-binding agents: a selective vulnerability of certain neurons to the disruption of microtubules. Author(s): Steward O, Goldschmidt RB, Sutula T. Source: Life Sciences. 1984 July 2; 35(1): 43-51. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=6738304

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Neutrophilic leukocyte inclusions in colchicine intoxication. Author(s): Powell HC, Wolf PL. Source: Archives of Pathology & Laboratory Medicine. 1976 March; 100(3): 136-8. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=175763

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Nucleoside transport in mammalian cells. Inhibition by colchicine. Author(s): Mizel SB, Wilson L. Source: Biochemistry. 1972 July 4; 11(14): 2573-8. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=5065219

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Occupancy approach to colchicine dosage. Author(s): Orr JS. Source: Lancet. 1971 January 9; 1(7689): 88. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=4099261

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Occupancy approach to colchicine dosage. Author(s): Wallace SL, Ertel NH. Source: Lancet. 1970 December 12; 2(7685): 1250-1. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=4098674

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Of liver, whisky and plants: a requiem for colchicine in alcoholic cirrhosis? Author(s): Lonardo A, Loria P. Source: European Journal of Gastroenterology & Hepatology. 2002 April; 14(4): 355-8. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11943945

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Old drugs with new uses. Colchicine for treatment of recurrent pericarditis. Author(s): Adolph RJ. Source: Circulation. 1990 October; 82(4): 1505-6. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=2401079

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On colchicine toxicity. Author(s): Varga J. Source: Clin Exp Rheumatol. 1984 October-December; 2(4): 357. No Abstract Available. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=6532627

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Oral absorption characteristics and pharmacokinetics of colchicine in healthy volunteers after single and multiple doses. Author(s): Ferron GM, Rochdi M, Jusko WJ, Scherrmann JM. Source: Journal of Clinical Pharmacology. 1996 October; 36(10): 874-83. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=8930773

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Outpatient colchicine poisoning. Author(s): Hoffman RS, Shih RD, Baruch JM. Source: Del Med J. 1993 April; 65(4): 257-60. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=8467932

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Overdose of colchicine in a three-year-old child. Author(s): Valenzuela P, Paris E, Oberpauer B, Rios JC, Concha F. Source: Vet Hum Toxicol. 1995 August; 37(4): 366-7. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=8540232

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Paradoxical effects of colchicine on the activation of human neutrophilis by chemotactic factors and inflammatory microcrystal. Author(s): Roberge CJ, Gaudry M, Gilbert C, Malawista SE, de Medicis R, Lussier A, Poubelle PE, Naccache PH. Source: Journal of Leukocyte Biology. 1996 June; 59(6): 864-71. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=8691072

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Permanent improvement of renal dysfunction and proteinuria with colchicine in a patient with tumoral amyloidosis and basal cell carcinoma. Author(s): Balal M, Seyrek N, Karayaylali I, Paydas S. Source: Renal Failure. 2003 July; 25(4): 677-80. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12911175

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P-glycoprotein-mediated colchicine resistance in different cell lines correlates with the effects of colchicine on P-glycoprotein conformation. Author(s): Druley TE, Stein WD, Ruth A, Roninson IB. Source: Biochemistry. 2001 April 10; 40(14): 4323-31. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11284688

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Pharmacokinetics and absolute bioavailability of colchicine after i.v. and oral administration in healthy human volunteers and elderly subjects. Author(s): Rochdi M, Sabouraud A, Girre C, Venet R, Scherrmann JM. Source: European Journal of Clinical Pharmacology. 1994; 46(4): 351-4. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=7957521

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Phase I trial and pharmacokinetics of the tubulin inhibitor 1069C85--a synthetic agent binding at the colchicine site designed to overcome multidrug resistance. Author(s): Judson I, Briasoulis E, Raynaud F, Hanwell J, Berry C, Lacey H. Source: British Journal of Cancer. 1997; 75(4): 608-13. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=9052420

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Pilot tolerability studies of hydroxychloroquine and colchicine in Alzheimer disease. Author(s): Aisen PS, Marin DB, Brickman AM, Santoro J, Fusco M. Source: Alzheimer Disease and Associated Disorders. 2001 April-June; 15(2): 96-101. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11403336

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Preferential sensitivity of acrocentric chromosomes to the aneugenic effect of colchicine. Author(s): Caria H, Chaveca T, Rueff J. Source: Teratogenesis, Carcinogenesis, and Mutagenesis. 1996; 16(5): 243-52. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=9122890

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Preliminary results of a two-center trial with colchicine for the treatment of chronic hepatitis B. Author(s): Floreani A, Colloredo G, Lobello S, Di Marco M, Popovic A, Naccarato R. Source: The American Journal of Gastroenterology. 2001 December; 96(12): 3451-2. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11774977

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Preventing acute gout when starting allopurinol therapy. Colchicine or NSAIDS? Author(s): Lewin G. Source: The Medical Journal of Australia. 1993 December 6-20; 159(11-12): 833. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=8264482

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Preventing acute gout when starting allopurinol therapy. Colchicine or NSAIDS? Author(s): Kelmann V. Source: The Medical Journal of Australia. 1993 December 6-20; 159(11-12): 833-4. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=8123131

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Preventing acute gout when starting allopurinol therapy. Colchicine or NSAIDs? Author(s): Kot TV, Day RO, Brooks PM. Source: The Medical Journal of Australia. 1993 August 2; 159(3): 182-4. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=8336619

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Prevention of acute attacks of pseudogout with oral colchicine. Author(s): Gonzalez T, Gantes M. Source: The Journal of Rheumatology. 1987 June; 14(3): 632-3. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=3625651

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Prevention of recurrences of corticosteroid-dependent idiopathic pericarditis by colchicine in an adolescent patient. Author(s): Brucato A, Cimaz R, Balla E. Source: Pediatric Cardiology. 2000 July-August; 21(4): 395-6. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=10865024

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Prevention of recurrent aphthous stomatitis with colchicine: an open trial. Author(s): Katz J, Langevitz P, Shemer J, Barak S, Livneh A. Source: Journal of the American Academy of Dermatology. 1994 September; 31(3 Pt 1): 459-61. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=8077473

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Probable colchicine-induced neutropenia not related to intentional overdose. Author(s): Dixon AJ, Wall GC. Source: The Annals of Pharmacotherapy. 2001 February; 35(2): 192-5. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11215839

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Psoriatic arthritis treated with oral colchicine. Author(s): Seideman P, Fjellner B, Johannesson A. Source: The Journal of Rheumatology. 1987 August; 14(4): 777-9. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=3668983

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Purpura annularis telangiectoides with vasculitic ulcers treated with colchicine. Author(s): Pandhi R, Jain R, Radotra BD, Kumar B. Source: International Journal of Dermatology. 2002 July; 41(7): 388-9. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12121548

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QSAR evaluation of the Ch'an Su and related bufadienolides against the colchicineresistant primary liver carcinoma cell line PLC/PRF/5(1). Author(s): Kamano Y, Yamashita A, Nogawa T, Morita H, Takeya K, Itokawa H, Segawa T, Yukita A, Saito K, Katsuyama M, Pettit GR. Source: Journal of Medicinal Chemistry. 2002 December 5; 45(25): 5440-7. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12459012

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Quantification of colchicine in body fluids by gallium chelate formation. Author(s): Bourdon R, Galliot M. Source: Acta Pharmacol Toxicol (Copenh). 1977; 41 Suppl 2: 219. No Abstract Available. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=162732

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Radioimmunoassay of colchicine with antisera exhibiting variable cross-reactivity. Author(s): Sabouraud A, Cano N, Scherrmann JM. Source: Therapeutic Drug Monitoring. 1994 April; 16(2): 179-85. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=8009567

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Rapid-onset colchicine myoneuropathy. Author(s): Schiff D, Drislane FW. Source: Arthritis and Rheumatism. 1992 December; 35(12): 1535-6. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=1472131

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Recurrent pericarditis. Relief with colchicine. Author(s): Guindo J, Rodriguez de la Serna A, Ramio J, de Miguel Diaz MA, Subirana MT, Perez Ayuso MJ, Cosin J, Bayes de Luna A. Source: Circulation. 1990 October; 82(4): 1117-20. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=2205414

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Regression of amyloidosis with colchicine in familial Mediterranean fever in an Ashkenazi patient. Author(s): Rozenbaum M, Rosner I. Source: Clin Exp Rheumatol. 1995 January-February; 13(1): 126. No Abstract Available. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=7774093

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Regression of nephrotic syndrome due to amyloidosis secondary to familial mediterranean fever following colchicine treatment. Author(s): Simsek B, Islek I, Simsek T, Kucukoduk S, Cengiz K. Source: Nephrology, Dialysis, Transplantation : Official Publication of the European Dialysis and Transplant Association - European Renal Association. 2000 February; 15(2): 281-2. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=10648685

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Regression of nephrotic syndrome in amyloidosis of familial mediterranean fever following colchicine treatment. Author(s): Livneh A, Shtrasburg S, Langevitz P. Source: Nephrology, Dialysis, Transplantation : Official Publication of the European Dialysis and Transplant Association - European Renal Association. 2000 October; 15(10): 1713-4. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11007856

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Regression of reactive systemic amyloidosis due to ankylosing spondylitis following the administration of colchicine. Author(s): Escalante A, Ehresmann GR, Quismorio FP Jr. Source: Arthritis and Rheumatism. 1991 July; 34(7): 920-2. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=2059239

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Regulation of type I collagen and interstitial collagenase mRNA expression in human dermal fibroblasts by colchicine and D-penicillamine. Author(s): Chung KY, Kang DS. Source: Yonsei Medical Journal. 1999 October; 40(5): 490-5. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=10565262

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Relationship of ADP-induced fibrinogen binding to platelet shape change and aggregation elucidated by use of colchicine and cytochalasin B. Author(s): Peerschke EI, Zucker MB. Source: Thrombosis and Haemostasis. 1980 February 29; 43(1): 58-60. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=7404479

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Renal function predicts colchicine toxicity: guidelines for the prophylactic use of colchicine in gout. Author(s): Wallace SL, Singer JZ, Duncan GJ, Wigley FM, Kuncl RW. Source: The Journal of Rheumatology. 1991 February; 18(2): 264-9. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=2023222

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Renal transplantation and pregnancy in a patient with familial Mediterranean fever amyloidosis taking triple-drug immunosuppression and colchicine. Author(s): Vergoulas G, Papagiannis A, Takoudas D, Papanikolaou V, Gakis D, Antoniadis A. Source: Nephrology, Dialysis, Transplantation : Official Publication of the European Dialysis and Transplant Association - European Renal Association. 1992; 7(3): 273-4. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=1315009

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Reporting a desensitization protocol for colchicine treatment. Author(s): Levinger U, Monselise A. Source: Clin Exp Rheumatol. 2001 September-October; 19(5 Suppl 24): S79. No Abstract Available. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11760410

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Reversal of nephrotic syndrome due to AA amyloidosis in psoriatic patients on longterm colchicine treatment. Case report and review of the literature. Author(s): Kagan A, Husza'r M, Frumkin A, Rapoport J. Source: Nephron. 1999; 82(4): 348-53. Review. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=10450037

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Reversal of the nephrotic syndrome by colchicine in amyloidosis of familial Mediterranean fever. Author(s): Zemer D, Livneh A, Langevitz P. Source: Annals of Internal Medicine. 1992 March 1; 116(5): 426. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=1736782

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Reversible acute cyclosporin nephrotoxicity induced by colchicine administration. Author(s): Menta R, Rossi E, Guariglia A, David S, Cambi V. Source: Nephrology, Dialysis, Transplantation : Official Publication of the European Dialysis and Transplant Association - European Renal Association. 1987; 2(5): 380-1. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=3122121

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Review: systemic toxicity associated with the intravenous administration of colchicine--guidelines for use. Author(s): Wallace SL, Singer JZ. Source: The Journal of Rheumatology. 1988 March; 15(3): 495-9. Review. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=3288754

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Rhabdomyolysis associated with gemfibrozil-colchicine therapy. Author(s): Atmaca H, Sayarlioglu H, Kulah E, Demircan N, Akpolat T. Source: The Annals of Pharmacotherapy. 2002 November; 36(11): 1719-21. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12398566

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Role of A-SAA in monitoring subclinical inflammation and in colchicine dosage in familial Mediterranean fever. Author(s): Duzova A, Bakkaloglu A, Besbas N, Topaloglu R, Ozen S, Ozaltin F, Bassoy Y, Yilmaz E. Source: Clin Exp Rheumatol. 2003 July-August; 21(4): 509-14. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12942707

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RPE-mediated collagen gel contraction. Inhibition by colchicine and stimulation by TGF-beta. Author(s): Raymond MC, Thompson JT. Source: Investigative Ophthalmology & Visual Science. 1990 June; 31(6): 1079-86. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=2354911

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Safety of colchicine in dialysis patients. Author(s): Anderson-Haag T, Patel B. Source: Seminars in Dialysis. 2003 September-October; 16(5): 412-3. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12969399

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Safety of colchicine therapy during pregnancy. Author(s): Michael O, Goldman RD, Koren G; Motherisk Team. Source: Can Fam Physician. 2003 August; 49: 967-9. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12943352

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Salicylates used in inflammatory bowel disease and colchicine impair interferongamma induced HLA-DR expression. Author(s): Crotty B, Hoang P, Dalton HR, Jewell DP. Source: Gut. 1992 January; 33(1): 59-64. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=1740279

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Secretion of lysyl oxidase by cultured human skin fibroblasts and effects of monensin, nigericin, tunicamycin and colchicine. Author(s): Kuivaniemi H, Ala-Kokko L, Kivirikko KI. Source: Biochimica Et Biophysica Acta. 1986 September 4; 883(2): 326-34. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=2874833

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Serum interleukin-2 and tumor necrosis factor-alpha in primary biliary cirrhosis: decrease by colchicine and relationship to HLA-DR4. Author(s): Miller LC, Kaplan MM. Source: The American Journal of Gastroenterology. 1992 April; 87(4): 465-70. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=1553933

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Severe respiratory muscle weakness related to long-term colchicine therapy. Author(s): Tanios MA, El Gamal H, Epstein SK, Hassoun PM. Source: Respiratory Care. 2004 February; 49(2): 189-91. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=14744269

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Severe sclerodermalike manifestations of the eosinophilia-myalgia syndrome despite concomitant colchicine therapy. Author(s): Lacour JP, Perrin C, Bodokh I, Ortonne JP. Source: Archives of Dermatology. 1991 November; 127(11): 1732-3. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=1952988

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Short-term administration of colchicine to haemodialysis patients: plasma beta-2microglobulin and phagocyte oxidative response. Author(s): Urena P, Nguyen AT, Jehenne G, Descamps-Latscha B, Drueke T, Basile C. Source: Nephron. 1990; 55(3): 348-50. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=2196477

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Sneddon-Wilkinson disease resistant to dapsone and colchicine successfully controlled with PUVA. Author(s): Khachemoune A, Blyumin ML. Source: Dermatology Online Journal [electronic Resource]. 2003 December; 9(5): 24. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=14996397

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Stability of E-rosettes in aged humans: effect of cytochalasin B and colchicine. Author(s): Brohee D, Kennes B, Neve P. Source: Mechanisms of Ageing and Development. 1983 November-December; 23(3-4): 383-93. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=6606742

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Structure-activity analysis of the interaction of curacin A, the potent colchicine site antimitotic agent, with tubulin and effects of analogs on the growth of MCF-7 breast cancer cells. Author(s): Verdier-Pinard P, Lai JY, Yoo HD, Yu J, Marquez B, Nagle DG, Nambu M, White JD, Falck JR, Gerwick WH, Day BW, Hamel E. Source: Molecular Pharmacology. 1998 January; 53(1): 62-76. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=9443933

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Structure-activity relationship of 1-propargyl-5-halopyrimidin-2-ones. Metaphase arresting properties and competitive inhibition of colchicine binding to tubulin. Author(s): Dornish JM, Oftebro R. Source: Investigational New Drugs. 1983; 1(3): 203-11. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=6678868

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Successful therapy with low-dose colchicine in intermittent hydrarthrosis. Author(s): Queiro-Silva R, Tinture-Eguren T, Lopez-Lagunas I. Source: Rheumatology (Oxford, England). 2003 February; 42(2): 391-2. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12595650

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Successful treatment of chronic Henoch-Schonlein purpura with colchicine and aspirin. Author(s): Padeh S, Passwell JH. Source: Isr Med Assoc J. 2000 June; 2(6): 482-3. No Abstract Available. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=10897246

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Successful treatment of familial Mediterranean fever attacks with thalidomide in a colchicine resistant patient. Author(s): Seyahi E, Ozdogan H, Masatlioglu S, Yazici H. Source: Clin Exp Rheumatol. 2002 July-August; 20(4 Suppl 26): S43-4. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12371635

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Successful use of colchicine in acute polyarticular pseudogout. Author(s): Meed SD, Spilberg I. Source: The Journal of Rheumatology. 1981 July-August; 8(4): 689-91. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=7299772

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Suppression of spermatogenesis in patients with Behcet's disease treated with cyclophosphamide and colchicine. Author(s): Fukutani K, Ishida H, Shinohara M, Minowada S, Niijima T, Hijikata K, Izawa Y. Source: Fertility and Sterility. 1981 July; 36(1): 76-80. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=6788612

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Survival of patients with primary (AL) amyloidosis. Colchicine-treated cases from 1976 to 1983 compared with cases seen in previous years (1961 to 1973). Author(s): Cohen AS, Rubinow A, Anderson JJ, Skinner M, Mason JH, Libbey C, Kayne H. Source: The American Journal of Medicine. 1987 June; 82(6): 1182-90. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=3605135

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Synchronization of Plasmodium falciparum in continuous in vitro culture: use of colchicine. Author(s): Hui GN, Palmer KL, Siddiqui WA. Source: The American Journal of Tropical Medicine and Hygiene. 1983 November; 32(6): 1451-3. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=6359912

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Synthesis of interleukin-1 beta in primary biliary cirrhosis: relationship to treatment with methotrexate or colchicine and disease progression. Author(s): Miller LC, Sharma A, McKusick AF, Tassoni JP, Dinarello CA, Kaplan MM. Source: Hepatology (Baltimore, Md.). 1995 August; 22(2): 518-24. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=7635420

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Ten-year combination treatment with colchicine and ursodeoxycholic acid for primary biliary cirrhosis: a double-blind, placebo-controlled trial on symptomatic patients. Author(s): Battezzati PM, Zuin M, Crosignani A, Allocca M, Invernizzi P, Selmi C, Villa E, Podda M. Source: Alimentary Pharmacology & Therapeutics. 2001 September; 15(9): 1427-34. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11552915

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The effect of colchicine treatment on spermatozoa: a cytogenetic approach. Author(s): Kastrop P, Kimmel I, Bancsi L, Weima S, Giltay J. Source: Journal of Assisted Reproduction and Genetics. 1999 October; 16(9): 504-7. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=10530407

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The effects of colchicine on neutrophil function in subjects with recurrent aphthous stomatitis. Author(s): Altinor S, Ozturkcan S, Hah MM. Source: Journal of the European Academy of Dermatology and Venereology : Jeadv. 2003 July; 17(4): 469-70. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12834466

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The effects of long-term therapy with colchicine on clinical and morphological features of liver cirrhosis. Author(s): Frysak Z, Dusek J, Jezdinska V. Source: Acta Univ Palacki Olomuc Fac Med. 1987; 116: 253-61. No Abstract Available. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=2962438

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The inhibitory effects of colchicine on cell proliferation and mineralisation in culture. Author(s): Salai M, Segal E, Cohen I, Dudkiewicz I, Farzame N, Pitaru S, Savion N. Source: The Journal of Bone and Joint Surgery. British Volume. 2001 August; 83(6): 9125. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11521938

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The role of colchicine in Helicobacter pylori prevalence and gastric mucosal changes in Behcet's Disease. Author(s): Pata C, Konica K, Yazar A. Source: The Journal of Rheumatology. 2001 September; 28(9): 2144. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11824425

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The role of colchicine in Helicobacter pylori prevalence and gastric mucosal changes in Behcet's disease. Author(s): Pata C, Konca K, Yazar A. Source: The Journal of Rheumatology. 2001 August; 28(8): 1938. Corrected and Republished In: http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11508610

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The role of colchicine in prevention of hepatic cirrhosis induced by carbon tetrachloride. Author(s): Rhoden EL, Pereira-Lima J, Rhoden CR, Mauri M, Pereira-Lima JC, Zettler CG, Barros EG. Source: Hepatogastroenterology. 1999 March-April; 46(26): 1111-5. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=10370676

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The stability of cytokeratin 18 in human liver cells during colchicine-induced microtubule disruption. Author(s): Liu Y, Su B, Pei R, Yeh C, Yeh K, Ying Lee K, Hsu Y, Ho C, Lai Y. Source: Food and Chemical Toxicology : an International Journal Published for the British Industrial Biological Research Association. 2001 January; 39(1): 85-9. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11259854

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Topical colchicine selection of keratinocytes transduced with the multidrug resistance gene (MDR1) can sustain and enhance transgene expression in vivo. Author(s): Pfutzner W, Terunuma A, Tock CL, Snead EK, Kolodka TM, Gottesman MM, Taichman L, Vogel JC. Source: Proceedings of the National Academy of Sciences of the United States of America. 2002 October 1; 99(20): 13096-101. Epub 2002 September 16. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12235361

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Topical colchicine therapy for actinic keratoses. Author(s): Grimaitre M, Etienne A, Fathi M, Piletta PA, Saurat JH. Source: Dermatology (Basel, Switzerland). 2000; 200(4): 346-8. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=10894974

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Topical therapy for actinic keratoses, II: Diclofenac, colchicine, and retinoids. Author(s): Tutrone WD, Saini R, Caglar S, Weinberg JM, Crespo J. Source: Cutis; Cutaneous Medicine for the Practitioner. 2003 May; 71(5): 373-9. Review. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12769404

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Toxic epidermal necrolysis-like reaction secondary to colchicine overdose. Author(s): Arroyo MP, Sanders S, Yee H, Schwartz D, Kamino H, Strober BE. Source: The British Journal of Dermatology. 2004 March; 150(3): 581-8. Review. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=15030347

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Treatment of chronic constipation with colchicine: randomized, double-blind, placebo-controlled, crossover trial. Author(s): Verne GN, Davis RH, Robinson ME, Gordon JM, Eaker EY, Sninksy CA. Source: The American Journal of Gastroenterology. 2003 May; 98(5): 1112-6. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12809836

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Treatment of linear IgA bullous dermatosis of childhood with colchicine. Author(s): Ang P, Tay YK. Source: Pediatric Dermatology. 1999 January-February; 16(1): 50-2. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=10028001

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Treatment of linear IgA bullous dermatosis of childhood with colchicine: in reply. Author(s): Tay YK, Ang P. Source: Pediatric Dermatology. 2000 March-April; 17(2): 157. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=10792813

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Treatment of Peyronie's disease with oral colchicine: long-term results and predictive parameters of successful outcome. Author(s): Kadioglu A, Tefekli A, Koksal T, Usta M, Erol H. Source: International Journal of Impotence Research : Official Journal of the International Society for Impotence Research. 2000 June; 12(3): 169-75. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11045911

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TrkA immunoreactivity in reactive astrocytes in human neurodegenerative diseases and colchicine-treated rats. Author(s): Aguado F, Ballabriga J, Pozas E, Ferrer I. Source: Acta Neuropathologica. 1998 November; 96(5): 495-501. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=9829813

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Troponin I as a marker of cardiac toxicity in acute colchicine overdose. Author(s): Mullins ME, Robertson DG, Norton RL. Source: The American Journal of Emergency Medicine. 2000 October; 18(6): 743-4. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11043640

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Unfavourable effects of colchicine in combination with interferon-alpha in the treatment of chronic hepatitis C. Author(s): Angelico M, Cepparulo M, Barlattani A, Liuti A, Gentile S, Hurtova M, Ombres D, Guarascio P, Rocchi G, Angelico F. Source: Alimentary Pharmacology & Therapeutics. 2000 November; 14(11): 1459-67. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11069317

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Update on colchicine and its mechanism of action. Author(s): Molad Y. Source: Curr Rheumatol Rep. 2002 June; 4(3): 252-6. Review. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12010611

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Urological evaluation of Behcet patients and the effect of colchicine on fertility. Author(s): Sarica K, Suzer O, Gurler A, Baltaci S, Ozdiler E, Dincel C. Source: European Urology. 1995; 27(1): 39-42. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=7744140

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Use of colchicine and steroids in the treatment of alcoholic liver disease. Author(s): Galambos JT, Riepe SP. Source: Recent Dev Alcohol. 1984; 2: 181-94. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=6374780

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Use of colchicine in the management of erythema nodosum leprosum (ENL). Author(s): Sarojini PA, Mshana RN. Source: Lepr Rev. 1983 June; 54(2): 151-3. No Abstract Available. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=6888142

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Use of colchicine in the treatment of Behcet's disease. Author(s): Harper RM, Allen BS. Source: International Journal of Dermatology. 1982 November; 21(9): 551-4. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=7152780

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Use of colchicine to treat severe constipation in developmentally disabled patients. Author(s): Frame PS, Dolan P, Kohli R, Eberly SW. Source: The Journal of the American Board of Family Practice / American Board of Family Practice. 1998 September-October; 11(5): 341-6. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=9796763

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Use of granulocyte colony-stimulating factor in the treatment of pancytopenia secondary to colchicine overdose. Author(s): Katz R, Chuang LC, Sutton JD. Source: The Annals of Pharmacotherapy. 1992 September; 26(9): 1087-8. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=1384817

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Use of intravenous colchicine for podagra. Author(s): Guazzo E. Source: American Family Physician. 1999 December; 60(9): 2504, 2507. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=10605985

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Use of intravenous colchicine in patients with acute gout. Author(s): Stephan WH. Source: American Family Physician. 2000 April 15; 61(8): 2343-4. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=10794578

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Use of oral colchicine in low-back pain. Author(s): Rask MR. Source: Spine. 1988 October; 13(10): 1201. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=2974628

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Vinblastine: colchicine-like effects on human blood leukocytes during phagocytosis. Author(s): Malawista SE. Source: Blood. 1971 May; 37(5): 519-29. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=5554211

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Visual prognosis in patients with Behcet's disease receiving colchicine, systemic corticosteroid or cyclosporin. Author(s): Hayasaka S, Kawamoto K, Noda S, Kodama T. Source: Ophthalmologica. Journal International D'ophtalmologie. International Journal of Ophthalmology. Zeitschrift Fur Augenheilkunde. 1994; 208(4): 210-3. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=7970549

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Waterhouse-Friderichsen syndrome resulting from colchicine overdose. Author(s): Stringfellow HF, Howat AJ, Temperley JM, Phillips M. Source: Journal of the Royal Society of Medicine. 1993 November; 86(11): 680. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=8258815

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We need more studies on colchicine and airway reactivity. Author(s): Fee WH Jr. Source: Chest. 1995 August; 108(2): 589. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=7634915

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Zero-order absorption and linear disposition of oral colchicine in healthy volunteers. Author(s): Thomas G, Girre C, Scherrmann JM, Francheteau P, Steimer JL. Source: European Journal of Clinical Pharmacology. 1989; 37(1): 79-84. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=2591469

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

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

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Adapted from http://ods.od.nih.gov. IBIDS is produced by the Office of Dietary Supplements (ODS) at the National Institutes of Health to assist the public, healthcare providers, educators, and researchers in locating credible, scientific information on dietary supplements. IBIDS was developed and will be maintained through an interagency partnership with the Food and Nutrition Information Center of the National Agricultural Library, U.S. Department of Agriculture.

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

Developing a model of colchicine neuropathy. Author(s): Division of Plastic Surgery, Department of Neurological Surgery, Johns Hopkins University School of Medicine, 3333 North Calvert Street, Baltimore, MD 21218, USA. Source: Chang, Ed Dellon, A Lee Dellon, Evan S Hendrickson, Mark E Microsurgery. 2002; 22(2): 46-8 0738-1085

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Effects of colchicine on parotid gland: structural and biochemical studies. Author(s): Department of Histology A, Faculty of Dentistry, University of Cordoba, Argentina. Source: Malberti, A I Gonzalez de Crosa, M Acta-Odontol-Latinoam. 1998; 11(1): 73-83 0326-4815

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Evaluation of commercial Ginkgo biloba dietary supplements for the presence of colchicine by high-performance liquid chromatography. Author(s): Program for Collaborative Research in the Pharmaceutical Sciences, College of Pharmacy, University of Illinois at Chicago, 60612, USA. Source: Li, W Fitzloff, J F Farnsworth, N R Fong, H H Phytomedicine. 2002 July; 9(5): 442-6 0944-7113

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Increase in thebaine content of Papaver bracteatum after colchicine treatment of seeds. Source: Wold, J.K. Paulsen, B.S. Laane, M.M. Haugli, T. Nordal, A. Plant-Med. Stuttgart, W. Ger. : Georg Thieme Verlag. December 1990. volume 56 (6) page 597-598. 0032-0943

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Induction of nephrotoxic serum nephritis in inbred mice and suppressive effect of colchicine on the development of this nephritis. Author(s): Department of Drug Information and Communication, Graduate School of Pharmaceutical Sciences, Chiba University, Chiba-shi, Japan. Source: Chen, S M Mukoyama, T Sato, N Yamagata, S Arai, Y Satoh, N Ueda, S Pharmacol-Res. 2002 April; 45(4): 319-24 1043-6618

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Meiotic telomere clustering is inhibited by colchicine but does not require cytoplasmic microtubules. Author(s): Department of Plant and Microbial Biology, University of California Berkeley, Berkeley, CA 94720-3200, USA. Source: Cowan, C R Cande, W Z J-Cell-Sci. 2002 October 1; 115(Pt 19): 3747-56 0021-9533

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Passive mechanical behavior of human neutrophils: effects of colchicine and paclitaxel. Author(s): Department of Pharmacology and Physiology, University of Rochester School of Medicine and Dentistry, New York 14642, USA. [email protected] Source: Tsai, M A Waugh, R E Keng, P C Biophys-J. 1998 June; 74(6): 3282-91 0006-3495

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Regionally selective neurotoxicity of NMDA and colchicine is independent of hippocampal neural circuitry. Author(s): Laboratory of Chemical Pharmacology, Graduate School of Pharmaceutical Sciences, The University of Tokyo, 7-3-1 Hongo, Bunkyo-ku, Tokyo 113-0033, Japan. [email protected] Source: Ikegaya, Y Matsuki, N Neuroscience. 2002; 113(2): 253-6 0306-4522

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The other physician behind the use of colchicine for the treatment of familial Mediterranean fever. Author(s): Division of Rheumatology, Department of Medicine, Istanbul Medical Faculty, University of Istanbul, Turkey. Source: Aral, O Ozdogan, H Yazici, H Clin-Exp-Rheumatol. 2001 Sep-October; 19(5 Suppl 24): S13-4 0392-856X

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 colchicine; 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 B12 Source: Healthnotes, Inc.; www.healthnotes.com Vitamin B12 Source: Prima Communications, Inc.www.personalhealthzone.com

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Minerals Potassium Source: Healthnotes, Inc.; www.healthnotes.com Potassium Source: Prima Communications, Inc.www.personalhealthzone.com

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

(-)-Phenylahistin arrests cells in mitosis by inhibiting tubulin polymerization. Author(s): Kanoh K, Kohno S, Katada J, Takahashi J, Uno I. Source: J Antibiot (Tokyo). 1999 February; 52(2): 134-41. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=10344567

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A new glycoside, 3-O-demethylcolchicine-3-O-alpha-d-glucopyranoside, from Gloriosa superba seeds. Author(s): Suri OP, Gupta BD, Suri KA, Sharma AK, Satti NK. Source: Natural Product Letters. 2001; 15(4): 217-9. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11833615

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Altered expression of ubiquitous kinesin heavy chain results in resistance to etoposide and hypersensitivity to colchicine: mapping of the domain associated with drug response. Author(s): Axenovich SA, Kazarov AR, Boiko AD, Armin G, Roninson IB, Gudkov AV.

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Source: Cancer Research. 1998 August 1; 58(15): 3423-8. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=9699675 •

Atractylodes lancea autotetraploids induced by colchicine treatment of shoot cultures. Author(s): Hiraoka N. Source: Biological & Pharmaceutical Bulletin. 1998 May; 21(5): 479-83. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=9635504

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Chromosomal composition of micronuclei in mouse NIH 3T3 cells treated with acrylamide, extract of Tripterygium hypoglaucum (level) hutch, mitomycin C and colchicine, detected by multicolor FISH with centromeric and telomeric DNA probes. Author(s): Jie YM, Jia C. Source: Mutagenesis. 2001 March; 16(2): 145-9. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11230557

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Colchicine and griseofulvin inhibit VCAM-1 expression on human vascular endothelial cells - evidence for the association of VCAM-1 expression with microtubules. Author(s): Asahina A, Tada Y, Nakamura K, Tamaki K. Source: Journal of Dermatological Science. 2001 January; 25(1): 1-9. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11154858

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Colchicine inhibits GABA(A) receptors independently of microtubule depolymerization. Author(s): Bueno OF, Leidenheimer NJ. Source: Neuropharmacology. 1998; 37(3): 383-90. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=9681936

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Colchicine poisoning by accidental ingestion of meadow saffron (Colchicum autumnale): pathological and medicolegal aspects. Author(s): Klintschar M, Beham-Schmidt C, Radner H, Henning G, Roll P. Source: Forensic Science International. 1999 December 20; 106(3): 191-200. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=10680067

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Colchicine toxicity: distinct morphologic findings in gastrointestinal biopsies. Author(s): Iacobuzio-Donahue CA, Lee EL, Abraham SC, Yardley JH, Wu TT. Source: The American Journal of Surgical Pathology. 2001 August; 25(8): 1067-73. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11474292

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Combined treatment with colchicine and Herba Taraxaci (Tarazacum mongolicum Hand.-Mazz.) attenuates Behcet's disease-like symptoms in mice and influences the expressions of cytokines. Author(s): Sohn S, Bang D, Lee SI, Kim YA, Lee ES, Ha JY, Kim JH, Choi SY, Lee S.

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Source: International Immunopharmacology. 2003 May; 3(5): 713-21. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12757740 •

Comparative molecular field analysis of colchicine inhibition and tubulin polymerization for combretastatins binding to the colchicine binding site on betatubulin. Author(s): Brown ML, Rieger JM, Macdonald TL. Source: Bioorganic & Medicinal Chemistry. 2000 June; 8(6): 1433-41. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=10896120

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Comparison of enterotoxicity between autumn crocus (Colchicum autumnale L.) and colchicine in the guinea pig and mouse : enterotoxicity in the guinea pig differs from that in the mouse. Author(s): Yamada M, Kobayashi Y, Furuoka H, Matsui T. Source: The Journal of Veterinary Medical Science / the Japanese Society of Veterinary Science. 2000 August; 62(8): 809-13. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=10993176

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Complexation and ionophoric properties of taxol and colchicine: complex formation and transport of sodium, potassium, magnesium and calcium ions across a liquid membrane. Author(s): Blaghen M, Lahlou N, Dzairi FZ, Moutaouakkil A, Talbi M. Source: Natural Toxins. 1999; 7(5): 179-85. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=10945480

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Determination of colchicine content in Colchicum hierosolymitanum and Colchicum tunicatum under cultivation. Author(s): Al-Fayyad M, Alali F, Alkofahi A, Tell A. Source: Natural Product Letters. 2002 December; 16(6): 395-400. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12462344

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Determination of colchicine in Colchicum steveni and C. hierosolymitanum (Colchicaceae): comparison between two analytical methods. Author(s): Alali F, Tawaha K, Qasaymeh RM. Source: Phytochemical Analysis : Pca. 2004 January-February; 15(1): 27-9. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=14979523

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Dissecting cellular processes using small molecules: identification of colchicine-like, taxol-like and other small molecules that perturb mitosis. Author(s): Haggarty SJ, Mayer TU, Miyamoto DT, Fathi R, King RW, Mitchison TJ, Schreiber SL.

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Source: Chemistry & Biology. 2000 April; 7(4): 275-86. Erratum In: Chem Biol 2001 December; 8(12): 1265. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=10780927 •

Distances between the paclitaxel, colchicine, and exchangeable GTP binding sites on tubulin. Author(s): Han Y, Malak H, Chaudhary AG, Chordia MD, Kingston DG, Bane S. Source: Biochemistry. 1998 May 12; 37(19): 6636-44. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=9578547

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Evaluation of commercial ginkgo and echinacea dietary supplements for colchicine using liquid chromatography-tandem mass spectrometry. Author(s): Li W, Sun Y, Fitzloff JF, van Breemen RB. Source: Chemical Research in Toxicology. 2002 September; 15(9): 1174-8. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12230411

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Evaluation of commercial Ginkgo biloba dietary supplements for the presence of colchicine by high-performance liquid chromatography. Author(s): Li W, Fitzloff JF, Farnsworth NR, Fong HH. Source: Phytomedicine : International Journal of Phytotherapy and Phytopharmacology. 2002 July; 9(5): 442-6. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12222666

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Identification of colchicine in placental blood from patients using herbal medicines. Author(s): Petty HR, Fernando M, Kindzelskii AL, Zarewych BN, Ksebati MB, Hryhorczuk LM, Mobashery S. Source: Chemical Research in Toxicology. 2001 September; 14(9): 1254-8. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11559040

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Inhibition of delayed hypersensitivity reactions by colchicine. II. Colchicine inhibits interferon-gamma induced expression of HLA-DR on gut epithelial cell line. Author(s): Mekori YA, Chowers Y, Ducker I, Klajman A. Source: Clinical and Experimental Immunology. 1989 November; 78(2): 230-2. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12412754

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Meiotic telomere clustering is inhibited by colchicine but does not require cytoplasmic microtubules. Author(s): Cowan CR, Cande WZ. Source: Journal of Cell Science. 2002 October 1; 115(Pt 19): 3747-56. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12235285

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Microsome-mediated transformation of O-methylandrocymbine to demecolcine and colchicine. Author(s): Rueffer M, Zenk MH. Source: Febs Letters. 1998 October 30; 438(1-2): 111-3. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=9821969

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Microtubule cytoskeleton perturbation induced by taxol and colchicine affects chaperonin containing TCP-1 (CCT) subunit gene expression in Tetrahymena cells. Author(s): Casalou C, Cyrne L, Rosa MR, Soares H. Source: Biochimica Et Biophysica Acta. 2001 November 11; 1522(1): 9-21. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11718895

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Multidrug resistance increment in a human colon carcinoma cell line by colchicine. Author(s): Ruiz Gomez MJ, Gil L, Souviron A, Martinez Morillo M. Source: J Physiol Biochem. 2000 March; 56(1): 33-8. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=10879679

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Near fatal acute colchicine intoxication in a child. A case report. Author(s): Goldbart A, Press J, Sofer S, Kapelushnik J. Source: European Journal of Pediatrics. 2000 December; 159(12): 895-7. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11131346

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Neuroprotective action of flavopiridol, a cyclin-dependent kinase inhibitor, in colchicine-induced apoptosis. Author(s): Jorda EG, Verdaguer E, Canudas AM, Jimenez A, Bruna A, Caelles C, Bravo R, Escubedo E, Pubill D, Camarasa J, Pallas M, Camins A. Source: Neuropharmacology. 2003 October; 45(5): 672-83. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12941380

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Passive mechanical behavior of human neutrophils: effects of colchicine and paclitaxel. Author(s): Tsai MA, Waugh RE, Keng PC. Source: Biophysical Journal. 1998 June; 74(6): 3282-91. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=9635782

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P-glycoprotein is more efficient at limiting uptake than inducing efflux of colchicine and vinblastine in HL-60 cells. Author(s): Decleves X, Chappey O, Boval B, Niel E, Scherrmann JM. Source: Pharmaceutical Research. 1998 May; 15(5): 712-8. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=9619779

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P-glycoprotein, glutathione and glutathione S-transferase increase in a colon carcinoma cell line by colchicine. Author(s): Ruiz-Gomez MJ, Souviron A, Martinez-Morillo M, Gil L. Source: J Physiol Biochem. 2000 December; 56(4): 307-12. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11321524

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Rapid colchicine competition-binding scintillation proximity assay using biotinlabeled tubulin. Author(s): Tahir SK, Kovar P, Rosenberg SH, Ng SC. Source: Biotechniques. 2000 July; 29(1): 156-60. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=10907090

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Recent progress in structure-activity relationship studies on the anticancer drug colchicine and its analogues. Author(s): Pan XD, Fang WS. Source: Yao Xue Xue Bao. 2002 October; 37(10): 821-7. Review. No Abstract Available. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12567870

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Regulation of parathyroid hormone-related protein expression in a canine squamous carcinoma cell line by colchicine. Author(s): Grone A, Weckmann MT, Capen CC, Rosol TJ. Source: Experimental and Toxicologic Pathology : Official Journal of the Gesellschaft Fur Toxikologische Pathologie. 1998 September; 50(4-6): 365-70. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=9784008

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Tamoxifen and colchicine-modulated vinblastine followed by 5-fluorouracil in advanced renal cell carcinoma: a phase II study. Author(s): Liu JH, Yang MH, Fan FS, Yen CC, Wang WS, Chang YH, Chen KK, Chen PM. Source: Urology. 2001 April; 57(4): 650-4. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11306370

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The history of colchicine. Author(s): Weinberger A, Pinkhas J. Source: Korot. 1980 June; 7(11-12): 760-3. No Abstract Available. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11630729

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The interaction of the B-ring of colchicine with alpha-tubulin: a novel footprinting approach. Author(s): Chaudhuri AR, Seetharamalu P, Schwarz PM, Hausheer FH, Luduena RF. Source: Journal of Molecular Biology. 2000 November 10; 303(5): 679-92. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11061968

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The microtubule depolymerizing drugs nocodazole and colchicine inhibit the uptake of Listeria monocytogenes by P388D1 macrophages. Author(s): Kuhn M. Source: Fems Microbiology Letters. 1998 March 1; 160(1): 87-90. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=9495017

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Verapamil sensitisation to alkaloids on colchicine-selected human colon adenocarcinoma cells. Author(s): Ruiz Gomez MJ, Souviron A, Gil L, Martinez Morillo M. Source: J Physiol Biochem. 2001 December; 57(4): 343-4. No Abstract Available. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12005037

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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AOL: http://search.aol.com/cat.adp?id=169&layer=&from=subcats

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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 colchicine; 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 Cirrhosis Source: Integrative Medicine Communications; www.drkoop.com

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Gout Source: Healthnotes, Inc.; www.healthnotes.com Gout Source: Integrative Medicine Communications; www.drkoop.com Liver Disease Source: Integrative Medicine Communications; www.drkoop.com Low Back Pain Source: Healthnotes, Inc.; www.healthnotes.com Osteoarthritis Source: Healthnotes, Inc.; www.healthnotes.com Pericarditis Source: Integrative Medicine Communications; www.drkoop.com Tendinitis Source: Integrative Medicine Communications; www.drkoop.com •

Herbs and Supplements Beta-Carotene Source: Healthnotes, Inc.; www.healthnotes.com Betula Alternative names: Birch; Betula sp. Source: Alternative Medicine Foundation, Inc.; www.amfoundation.org Centella Alternative names: Gotu Kola; Centella asiatica (Linn.) Source: Alternative Medicine Foundation, Inc.; www.amfoundation.org Colchicine Source: Healthnotes, Inc.; www.healthnotes.com Colchicine Source: Prima Communications, Inc.www.personalhealthzone.com Lepidium Sp Alternative names: Cress; Lepidium sp. Source: Alternative Medicine Foundation, Inc.; www.amfoundation.org Sanguinaria Alternative names: Bloodroot; Sanguinaria canadensis L. Source: Alternative Medicine Foundation, Inc.; www.amfoundation.org Thuja Plicata Alternative names: Western Red Cedar Source: Alternative Medicine Foundation, Inc.; www.amfoundation.org

Alternative Medicine 83

Uricosuric Agents Source: Integrative Medicine Communications; www.drkoop.com

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 COLCHICINE Overview In this chapter, we will give you a bibliography on recent dissertations relating to colchicine. 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 “colchicine” (or a synonym) in their titles. To accurately reflect the results that you might find while conducting research on colchicine, we have not necessarily excluded non-medical dissertations in this bibliography.

Dissertations on Colchicine 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 colchicine. 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: •

Part I. Design and synthesis of type I signal peptidase inhibitors. Part II. Pharmacophore search of the colchicine binding site of tubulin and using diverse solutions to find new colchicine binding drugs by Gourley, Maralea Jean, PhD from THE UNIVERSITY OF MISSISSIPPI, 2003, 126 pages http://wwwlib.umi.com/dissertations/fullcit/3115433

•

The biogenesis of colchicine and fusaric acid by Hill, R. D; PhD from THE UNIVERSITY OF MANITOBA (CANADA), 1965 http://wwwlib.umi.com/dissertations/fullcit/NK00132

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The effects of hypothyroidism, colchicine and adriamycin on the dorsal root ganglia of rats at critical periods of postnatal development an ultrastructural study by Eddy, Ertrice L; PhD from THE UNIVERSITY OF MANITOBA (CANADA), 1980 http://wwwlib.umi.com/dissertations/fullcit/NK43072

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The use of colchicine in the rat to investigate a trophic influence of the motor nerve by Fried, Joseph Andreas; PhD from MCMASTER UNIVERSITY (CANADA), 1977 http://wwwlib.umi.com/dissertations/fullcit/NK32991

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Ultrastructural features of the Harding-Passey melanoma following maximal, minimal and intermittent colchicine chemotherapy by Loader, Kenneth Robert; PhD from THE UNIVERSITY OF MANITOBA (CANADA), 1973 http://wwwlib.umi.com/dissertations/fullcit/NK15517

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. PATENTS ON COLCHICINE 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.8 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 “colchicine” (or a synonym) in their titles. To accurately reflect the results that you might find while conducting research on colchicine, we have not necessarily excluded non-medical patents in this bibliography.

Patents on Colchicine By performing a patent search focusing on colchicine, 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 will tell you how to obtain this information later in the chapter. The following is an 8Adapted

from the United States Patent and Trademark Office: http://www.uspto.gov/web/offices/pac/doc/general/whatis.htm.

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example of the type of information that you can expect to obtain from a patent search on colchicine: •

Allocolchinones and uses thereof Inventor(s): Gorbunoff; Marina J. (Wellesley, MA), Perez-Ramirez; Bernardo (Brookline, MA), Timasheff; Serge M. (Wellesley, MA) Assignee(s): Brandeis University (Waltham, MA) Patent Number: 5,760,092 Date filed: March 11, 1996 Abstract: Disclosed are allocolchinones, which are anti-mitotic agents. Allocolchinones bind to tubulin reversibly and are more effective at inhibiting microtubule formation than colchicine. 7-Acetamido-allocolchinone inhibits the growth of a number of tumor cell lines at concentrations about 100 times lower than colchicine. Also disclosed is a method of treating an individual with cancer by administering a composition which comprises a therapeutically effective amount of an allocolchinone which inhibits microtubule assembly. Administering a therapeutically effective amount of a composition which comprises an allocolchinone which inhibits microtubule assembly can also be used for treating inflammatory diseases, multiple sclerosis, primary biliary cirrhosis, Alzheimer's Disease and Behcet's Disease. Excerpt(s): Colchicine binds to the protein tubulin irreversibly. Tubulin is part of the cellular cytoskeleton, of the mitotic apparatus, of neurons and a building block of microtubules. The binding of colchicine to tubulin interferes with microtubuledependent cell processes. One important example of a microtubule-dependent process with which colchicine interferes is the assembly of microtubules during metaphase. Inhibition of microtubule assembly results in the inability of a cell to move its chromosomes during cell division causing the cell to arrest during metaphase and die. Consequently, colchicine acts as an anti-mitotic agent. Many anti-cancer drugs act by causing cell death during mitosis. However, the use of colchicine as an anti-cancer drug is precluded by its high toxicity. The toxicity of colchicine is thought to be due in part to the fact that colchicine binds irreversibly to tubulin. Consequently, the treatment of cancer could be greatly advanced with new drugs that inhibit microtubule assembly by binding to tubulin but which are less toxic than colchicine. Colchicine has long been used as an agent against inflammatory disease, such as gout and Mediterranean fever. Colchicine is also used to treat other diseases, such as multiple sclerosis, primary biliary cirrhosis, Alzheimer's Disease and Behcet's Disease. Thus, there is also a need for less toxic drugs having greater effectiveness with reduced side effects against these diseases. Web site: http://www.delphion.com/details?pn=US05760092__

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Colchicine derivatives and the therapeutical use thereof Inventor(s): Bombardelli; Ezio (Milan, IT), Gabetta; Bruno (Milan, IT) Assignee(s): Indena S.p.A. (Milan, IT) Patent Number: 5,843,910 Date filed: March 21, 1997 Abstract: The present invention relates to novel colchicine derivatives of formula (1), where Y is a --CH.sub.2 --CH--NH--R.sub.3 group or a --CH--CH.sub.2 OR.sub.3 group

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and the other variables are as defined in claim 1, having antiproliferative, antitumoral and anti-inflammatory activities. The novel compounds have a cytotoxicity on human tumoral cell lines comparable with colchicine, but, in comparison with the latter, they are less toxic and more selective, particularly on cells resistant to the usual medicaments. Some compounds have a marked activity on TNF and interleukine 2, and therefore are very potent anti-inflammatory agents. They can be included in pharmaceutical formulations useful for the parenteral, oral and topical administrations. Excerpt(s): The present invention relates to novel colchicine derivatives having antiproliferative, antitumoral and antiinflammatory activities, the methods for the preparation thereof and the pharmaceutical formulations containing them. Colchicine is a known pseudo-alkaloid widely used for a very long time in therapy for the treatment of gout; it acts very quickly and specifically, even though it should be used for short times due to its toxicity. In addition, colchicine is a very potent antiblastic agent, whose action is connected with a mechanism blocking the formation of the mitotic spindle in cell division; this latter aspect has been investigated thoroughly for any antitumoral activity and a great deal of colchicine derivatives have been prepared for this purpose. Colchicine as such and a number of its prepared derivatives cannot be used due to its high toxicity in terms of risk/benefit ratio. Only one colchicine derivative, demecolcine, is used in some degree in oncology for the treatment of some leukemia forms. As far as the use in the antiinflammatory field is concerned, the only marketed colchicine derivative is thiocolchicoside, bearing a thiomethyl moiety at C.sub.10 and a glucose molecule at the hydroxyl in C.sub.3; the therapeutical uses of this derivative are related to the muscle relaxant and antiphlogistic effects. The products of the invention differ from those of the prior art in the high therapeutical index. In the antitumoral field, researches have been focused on the research of products having, besides a normal cytotoxicity, a cytotoxicity aimed at cell lines resistant to the usual antiblastic medicaments. Web site: http://www.delphion.com/details?pn=US05843910__ •

Colchicine ophthalmic composition and method of use Inventor(s): Bhattacherjee; Parimal (Nyack, NY), Eakins; Kenneth E. (Sparkill, NY) Assignee(s): Nelson Research & Development Company (Irvine, CA) Patent Number: 4,190,673 Date filed: May 10, 1978 Abstract: A therapeutic composition comprising a topically administrable ophthalmic pharmaceutical carrier and colchicine. The foregoing composition temporarily alleviates the symptoms of glaucoma when topically administered to the eye. Excerpt(s): The invention relates generally to a composition and method for reducing intraocular pressure (IOP) in humans and animals. More particular, the invention relates to a method for temporarily alleviating the symptoms of glaucoma. Colchicine is a major alkaloid of Colchicum autumnale L., Libaceoe whose extraction procedure is wellknown in the art. Colchicine has been used heretofore in research on plant genetics and in the therapeutic treatment of gout and Familial Mediterranean Fever. Glaucoma is a condition of the eye characterized by increased intraocular pressure. Untreated, the condition eventually leads to irreversible retinal damage and blindness. Conventional therapy for glaucoma is with pilocarpine and/or epinephrine administered topically several times daily.

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Web site: http://www.delphion.com/details?pn=US04190673__ •

Colchicine-skeleton compounds, their use as medicaments and compositions containing them Inventor(s): Bombardelli; Ezio (Milan, IT) Assignee(s): Indena S.p.A. (Milan, IT) Patent Number: 6,080,739 Date filed: November 24, 1998 Abstract: The present invention relates to colchicine and thiocolchicine derivatives which can be obtained from these molecules by functionalization of the C-7 to ketone or functionalization of the amino group. Said compounds have a marked antiblastic activity both on the normal cancer cells and on the chemoresistant phenotype. The compounds of the invention can be administered both by injection and orally. Excerpt(s): The present invention relates to novel colchicine derivatives having antiproliferative, antineoplastic and antiinflammatory activities, the methods for the preparation thereof and the pharmaceutical formulations containing them. Colchicine is a known pseudo-alkaloid widely used for a very long time in therapy for the treatment of gout, a pathology on which it acts very quickly and specifically, even though it should be used for short times due to its toxicity. A colchicine derivative, namely thiocolchicoside, is widely used to treat contractures and in inflammatory conditions on skeletal muscles. In addition, colchicine is a very potent antiblastic agent, which acts blocking the formation of the mitotic spindle during cell division; this latter aspect has been investigated thoroughly for any antineoplastic activity and a great deal of colchicine derivatives have been prepared to this purpose. Colchicine as such and a number of its derivatives could not be used clinically due to their high toxicity, and therefore their unacceptable risk/benefit ratio. Only one colchicine derivative, demecoicine, is used in some degree in oncology for the treatment of some leukemia forms. Therefore the problem exist of the availability of antineoplastic medicaments having a satisfactory risk/benefit ratio, i.e. a high therapeutical activity with poor or no side-effects. Web site: http://www.delphion.com/details?pn=US06080739__

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Electrically hydrolyzed salines as in cardiomyopathy and multiple sclerosis

vivo

microbicides

for

treatment

of

Inventor(s): Morrow; Robert E. (Salt Lake City, UT) Assignee(s): Medical Discoveries, Inc. (Logan, UT) Patent Number: 5,334,383 Date filed: May 23, 1990 Abstract: A method of treating antigen related infections is disclosed which comprises subjecting a dilute normal saline solution to electrical hydrolysis with adequate voltage to produce a solution containing bioactive microbicidal atoms, radicals or ions selected from the group consisting of chloride , ozone, hydroxide, hypochlorite, peroxide, chlorine dioxide, and oxygen with corresponding amounts of molecular hydrogen and sodium and hydrogen ions. The solution is balanced to normal saline with hypertonic

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saline. The injecting of effective amounts of the balanced solution intravenously into a warm blooded animal affected by an antigenic related infection results in a microbicidal action which mimics or enhances action of the free radicals produced in vivo as a result of respiratory bursts. The balanced saline solution may be injected along with the administration of moderating and/or neutralizing amounts of antioxidants or reducing agents such as catalase, superoxide dismutase, MPO or other suitable peroxidase, glutathione, glutathione peroxidase, ascorbic acid or other suitable agents. The moderating antioxidants and/or neutralizing agents are preferably administered orally prior to the administration of the saline solution with additional amounts of ascorbic acid being administered intravenously following injection of the saline. The microbicidal effects of the saline solution may be enhanced by the coadministration of effective amounts of colchicine or other enhancing agents. Excerpt(s): This application relates to the in vivo antimicrobial use of electrically hydrolyzed salines. More particularly, this invention relates to the treatment of antigen related infections in warm blooded animals by the intravenous injection of electrically hydrolyzed saline solutions which mimic or enhance the naturally occurring chemicals produced in vivo by the body in responding to such infections. Phagocytic cells (neutrophils, monocytes, eosinophils, macrophages, and large granular lymphocytes, collectively called "killer cells") give off superoxide in what is called the "respiratory burst" which has an antimicrobial action and, if not properly controlled, can also cause tissue damage. The superoxide radical itself may not be directly responsible for the microbicidal action. Rather, this activity and any resultant tissue damage may be attributed to superoxide derivatives such as hydrogen peroxide, hydroxyl radical and possibly, singlet oxygen. Polymorphonuclear neutrophils and macrophages not only give off superoxide, leading to the production of hydrogen peroxide and hydroxyl free radical , but also generate hypohalous acids and N-chloroamines as one of their mechanisms which also destroy bacteria. These leukocytes consume oxygen which is transformed by membranous reduced nicotinamide adenine dinucleotide phosphate (NADPH) oxidase to superoxide. The "respiratory burst" is observed as a dramatic increase in the consumption of oxygen and the activation of a membrane-associated NADPH oxidase. This oxidase reduces molecular oxygen to superoxide anions, which in turn dismutates to hydrogen peroxide. Superoxide and hydrogen peroxide can interact to give rise to the hydroxyl radical and possibly also to singlet oxygen. The superoxide anion, hydrogen peroxide, hydroxide radicals and singlet oxygen, all possess antimicrobial activity and are quite unstable. The respiratory burst continues during phagocytosis by polymorphonuclear leukocytes until engulfment is complete. The respiratory burst may also occur in leukocytes under various chemical influences in addition to phagocytosis. Web site: http://www.delphion.com/details?pn=US05334383__ •

Estrogenic compounds as anti-angiogenic agents Inventor(s): D'Amato; Robert J. (Lancaster, PA), Folkman; Moses J. (Brookline, MA) Assignee(s): Children's Medical Center Corporation (Boston, MA) Patent Number: 5,504,074 Date filed: August 6, 1993 Abstract: The application discloses methods of treating mammalian diseases characterized by undesirable angiogenesis by administering estradiol derivatives including those comprising colchicine or combretastatin A-4 structural motifs of the

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general formulae found below in a dosage sufficient to inhibit cell mitosis. The application discloses novel compounds used in the methods. Excerpt(s): This invention relates to treating disease states characterized by abnormal cell mitosis. Cell mitosis is a multi-step process that includes cell division and replication (Alberts, B. et al. In The Cell, pp. 652-661 (1989); Stryer, E. Biochemistry (1988)). Mitosis is characterized by the intracellular movement and segregation of organelles, including mitotic spindles and chromosomes. Organelle movement and segregation are facilitated by the polymerization of the cell protein tubulin. Microtubules are formed from.alpha. and.beta. tubulin polymerization and the hydrolysis of guanosine triphosphate (GTP). Microtubule formation is important for cell mitosis, cell locomotion, and the movement of highly specialized cell structures such as cilia and flagella. Microtubules are extremely labile structures that are sensitive to a variety of chemically unrelated antimitotic drugs. For example, colchicine and nocadazole are anti-mitotic drugs that bind tubulin and inhibit tubulin polymerization (Stryer, E. Biochemistry (1988)). When used alone or in combination with other therapeutic drugs, colchicine may be used to treat cancer (WO-9303729-A, published Mar. 4, 1993; J03240726-A, published Oct. 28, 1991), alter neuromuscular function, change blood pressure, increase sensitivity to compounds affecting sympathetic neuron function, depress respiration, and relieve gout (Physician's Desk Reference, Vol. 47, p. 1487, (1993)). Web site: http://www.delphion.com/details?pn=US05504074__ •

G-banding of plant chromosomes Inventor(s): Hsu; Tao-Chiuh (Harris, TX) Assignee(s): The Board of Regents, The University of Texas System (Austin, TX) Patent Number: 4,596,089 Date filed: November 21, 1983 Abstract: A method for the staining of the chromosomal material of plant cells so as to induce G-Bands, useful in plant genetic studies such as hydridization. G-Banding is induced by contacting living plant cells, such as those of plants of the family Gramineae, with actinomycin D, N-methyl-N'-nitroguanidine or ethidium bromide. More particularly, plant cells are treated with AMD and colchicine before fixation, prepared for viewing through a microscope by staining and then mounted on a glass slide. Excerpt(s): The present invention relates to the staining of chromosomal material, and more particularly to the formation of G-Bands in plant chromosomes. Staining of chromatin for microscopic examination has long been used as a method for monitoring chromosomal changes or abnormalities in both plants and animals. Several techniques are available, each of which results in a specific pattern of bands of color deposition in the chromosomes. Among the best known banding techniques are those which induce the formation of C-Bands, G-Bands, and R-Bands. The term "C-Bands" is used to describe the light and dark bands which appear on the chromosomes when viewed through a microscope which are the result of treatment of the cells with certain known staining processes. The locations of these light and dark bands are specific for each specie from which the cells are taken. G-Bands are much finer than C-Bands, have specific widths, run longitudinally along the chromosomes and have specific intervals between bands. R-Bands are the reverse of G-Bands: dark G-Bands appear as light RBands and light G-Bands appear as dark R-Bands.

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Web site: http://www.delphion.com/details?pn=US04596089__ •

Inducing chromosome doubling in anther culture in maize Inventor(s): Jia; Xu (Institute of Genetics, Academia Sinica, Beijing, CN) Assignee(s): none reported Patent Number: 5,770,788 Date filed: June 6, 1995 Abstract: Fertile corn plants are produced by culturing anthers or pollen in the presence colchicine which is added to an otherwise ordinary anther culture medium after a preculture phase in the absence of the colchicine. The colchicine induces doubling of the chromosome numbers in regenerated plants which would otherwise be infertile haploids. Haploid doubling provides a rapid route to homozygous parental plant lines. Excerpt(s): This invention relates to a method of producing plants. More specifically the invention relates to a method of producing corn (Zea mays) plants for use as breeding stock in a plant breeding programme. Plant breeding comprises screening potential parental varieties for desirable characteristics and crossing selected parental lines to introduce those desirable characteristics into the progeny of the cross. One difficulty encountered by breeders is that, in the act of crossing, not only the desirable trait is transferred to the progeny but a a certain amount of randomization of the genomes of both parental lines occurs leading to a wide variety of morphology and other features of the progeny. This makes selection of the desired progeny difficult, particularly if expression of the desired trait is not visually obvious as this would necessitate laboratory analysis of the whole progeny generation. Detection of a genetically recessive trait is particularly difficult. To overcome this difficulty, breeders tend to work with homozygous parental lines (inbreds) so that the genetic make up of the F1 generation is more predictable. When a desirable trait is detected in a heterozyote, breeders have to subject the plant to a succession of back-crosses with its parent lines, followed by selection and further back-crossing. Eventually a plant is derived which is homozygous in the desired trait. Of course, the time scale involved here is dictated by the rate at which plants grow to maturity and set seed and several years can be necessary to produce the desired homozygous parent line. Web site: http://www.delphion.com/details?pn=US05770788__

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Induction of embryogenesis using cytoskeleton inhibitors or protein synthesis inhibitors Inventor(s): Newcombe; William (Battersea, CA), Simmonds; Daina H. (Nepean, CA) Assignee(s): Agri-Food Canada, a part interest (Ottawa, CA), Her Majesty the Queen in right of Canada, as represented by Agriculture (Ottawa, CA) Patent Number: 5,900,375 Date filed: March 29, 1996 Abstract: Embryogenesis from plant microspores is routinely induced with a 16-24 h temperature treatment of 32.5.degree. C. Continuous culture at 25.degree. C. results in pollen development. However, microspore treatment with anti-cytoskeletal agents, or protein synthesis inhibitors, at the non-inductive temperature of 25.degree. C., can

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induce embryogenesis, thus demonstrating that heat shock is not required for embryogenic induction. Furthermore, when anti-microtubule agents (e.g. colchicine) are used, embryo induction and chromosome doubling occur simultaneously, thus generating doubled haploids, whereas heat induction generates haploids. Thus, the use of microtubule inhibitors will provide a simple one-step process to simultaneously induce embryogenesis and chromosome doubling for the production of fertile plants, thus providing minimal manipulation which will be very advantageous for genetic studies and plant breeding programs. As noted, heat shock induces haploids. A low level of chromosome doubling can be obtained by adding colchicine to microspore cultures during the heat treatment. However, the use of trifluralin with the heat treatment, to generate doubled haploid plants results in an improved recovery of fertile doubled haploid plants than previously shown in the prior art. Excerpt(s): The present invention is directed to the use of cytoskeleton modifiers or protein synthesis inhibitors to induce embryogenesis from plant microspores. The production of haploid plants generated through either anther or isolated microspore culture has succeeded in over 240 species from 85 genera in 38 families (Srivastava and Johri 1988). Microspore culture of Brassica napus has become one of the most efficient embryogenic systems and has been exploited for developmental studies (e.g. Zaki and Dickinson 1991; Telmer et al. 1992, 1993, 1994), for mutagenesis and gene transfer (Swanson et al. 1989; Huang 1992), and for development of doubled haploid homozygous breeding lines (Chen and Beversdorf 1992). The use of haploid plants, generated from anther or microspore culture, has enhanced the efficiency of crop improvement programs (Collins and Genovesi 1982, Chen and Beversdorf 1992). Although haploid plants can be readily regenerated, the haploids cannot be used directly in genetic studies and breeding programs because they are sterile (Subrahmanyam and Kasha 1975). The current methods of doubling the chromosome complement of haploids to produce fertile homozygous doubled haploids are inefficient and labor intensive. Efficient induction of embryogenesis is necessary for developmental and biochemical studies. The efficiency of embryogenesis of B. napus has been improved by using donor plants grown at low temperatures (Keller et al. 1986), by optimizing the microspore culturing conditions (Keller et al. 1986; Lichter 1981; Fan et al. 1988; Chuong and Beaversdorf 1985; Kott et al. 1988; Gland et al. 1988; Huang et al. 1990) and by using microspores at the competent developmental stages (Telmer et al. 1992). Web site: http://www.delphion.com/details?pn=US05900375__ •

Inhibition of wound contraction with paclitaxel, colchicine and penicillamine Inventor(s): Joseph; Hazel L. (200 Winston Dr., Apt. 2806, Cliffside Park, NJ 07010) Assignee(s): none reported Patent Number: 5,916,913 Date filed: August 3, 1998 Abstract: The present invention uses Paclitaxel and/or Colchicine in an appropriate carrier to inhibit wound contraction. Paclitaxel is an antimicrotubule agent that is currently used as a cancer chemotherapeutic drug. Colchicine inhibits microtubule dependent processes such as cell contraction and motility. It has been given orally for decades to treat gout. Previous studies using Colchicine to control wound contraction have been unsuccessful because of both local and systemic toxicity. Studies using the present invention demonstrate that Paclitaxel and Colchicine, when applied to wounds

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locally (either topically or by injection) in concentrations which are much lower than those previously studied, inhibit wound contraction, collagen deposition and granulation tissue growth. When combined with D-penicillamine, a drug that inhibits collagen cross-linking, the combination inhibits wound contraction, granulation tissue growth (nascent tissue that forms in the wound immediately post-injury), and intramuscular collagen deposition; epithelialization (sealing of the wound) is promoted. Excerpt(s): This invention relates to a method and composition for controlling scar formation and more particularly to the use of Paclitaxel and/or Colchicine and/or penicillamine for the inhibition of wound contraction and scar overgrowth while enhancing epithelialization. Wound contraction is the primary process by which wounds decrease their surface area over time. In World War I, contaminated wounds were allowed to heal secondarily by contraction resulting in reduced wound infection and sepsis. Wound contraction, however, frequently results in contractures and functional impairment, the extent of which depends upon the size and location of the wound. Previous studies using systemic or local drug therapy to inhibit contraction have produced inconsistent results, and there is not a single drug that is effective in controlling wound contraction clinically. Contractile fibroblasts and nascent collagen in granulation tissue have been implicated as having an important role in initiating and maintaining wound contraction. Ehrlich, et al. EVIDENCE FOR THE INVOLVEMENT OF MICROTUBULES IN WOUND CONTRACTION, Am. J. Surg., Vol 133, pages 706709, 1977. Colchicine has been administered orally to treat scleroderma and coronary restenosis, albeit with limited efficacy, primarily because of systemic toxicity associated with prolonged use of this drug. Colchicine has been shown to stimulate collagenase activity. Colchicine also inhibits many microtubule dependent processes including but not limited to fibroblast cell contraction and motility. Ehrlich, et al., applied Colchicine (10.sup.-5 M) topically to granulating wounds in rabbits and demonstrated that it inhibited contraction but resulted in local tissue death and a tendency towards infection. More recently, however, Rennard et al., COLCHICINE SUPPRESSES THE RELEASE OF FIBROBLAST GROWTH FACTORS FROM ALVEOLAR MACROPHAGES IN VITRO, Am. Rev. Respir. Dis. Vol 137(1), pages 181-185, 1988, demonstrated that Colchicine (40 ng/ml and 100 ng/ml) significantly inhibits secretion of two mediators of fibroblast proliferation (fibronectin and a macro-phage-derived growth factor) in vitro with detectable inhibition in the range of 1-10 ng/ml. The effect of Colchicine was not due to nonspecific toxicity since macrophages treated with Colchicine were capable of de novo protein synthesis and secretion of several protein products, despite the fact that fibronectin and growth factor release were suppressed. Notable also is the recent work of Damji et al., PHARMACOLOGIC MODULATION OF HUMAN SUBCONJUNCTIVAL FIBROBLAST BEHAVIOR IN VITRO, Ophthalmic. Surg., Vol. 21, No. 1, pages 31-43, 1990, who demonstrated that Colchicine inhibited cell migration at 0.004,.mu.g/ml without cytotoxicity. These two studies prompted an evaluation of Colchicine, in vivo, at concentrations lower than 10.sup.-5 M, administering the drug by local injection. It was postulated that by injecting Colchicine at low concentrations directly into the wound, the toxicity associated with applying the drug topically could be eliminated. Web site: http://www.delphion.com/details?pn=US05916913__

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Prolonged local anesthesia with colchicine Inventor(s): Chasin; Mark (Manalapan, NJ), Goldenheim; Paul (Wilton, CT), Sackler; Richard (Greenwich, CT) Assignee(s): Euro-Celtique, S.A. (Luxembourg, LU) Patent Number: 5,747,060 Date filed: March 26, 1996 Abstract: A formulation for inducing sustained regional local anesthesia in a patient comprising a substrate comprising a local anesthetic and an effective amount of a biocompatible, biodegradable, controlled release material prolonging the release of the local anesthetic from the substrate to obtain a reversible nerve blockade when implanted or injected in a patient, and an amount of colchicine effective to prolong the duration of the local anesthesia for a time period longer than that obtainable from the substrate without colchicine. Excerpt(s): The present invention is related to biodegradable controlled release formulations for the administration of locally active drugs, in particular, sustained release local anesthetics in combination with colchicine for prolonging nerve block or numbness induced by a local anesthetic. While compounds utilized as general anesthetics reduce pain by producing a loss of consciousness, local anesthetics act to induce a loss of sensation in the localized area of administration in the body. The mechanism by which local anesthetics induce their effect, while not having been determined definitively, is generally thought to be based upon the ability to interfere with the initiation and transmission of the nerve impulse. The duration of action of a local anesthetics is proportional to the time during which it is in actual contact with the nervous tissues. Consequently, procedures or formulations that maintain localization of the drug at the nerve greatly prolong anesthesia. All local anesthetics are potentially toxic, and therefore it is of great importance that the choice of drug, concentration, rate and site of administration, as well as other actors, be considered in their use. On the other hand, a local anesthetic must remain at the site long enough to allow sufficient time for the localized pain to subside. Different devices and formulations are known in the art for administration of local anesthetics. For example, U.S. Pat. Nos. 4,725,442 and 4,622,219 (Haynes) are directed to microdroplets of methoxyflurane-containing microdroplets coated with a phospholipid prepared by sonication, which are suitable for intradermal or intravenous injection into a patient for inducing local anesthesia. Such microdroplets are said to cause long-term local anesthesia when injected intradermally, giving a duration of anesthesia considerably longer than the longest acting conventional local anesthetic (e.g., bupivacaine or dibucaine). Web site: http://www.delphion.com/details?pn=US05747060__

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Therapy for constipation Inventor(s): Borody; Thomas Julius (144 Great North Road, Five Dock NSW 2046, AU) Assignee(s): none reported Patent Number: 6,426,338 Date filed: December 17, 1999 Abstract: Compositions comprising colchicine and at least one amino-salicylic acid derivative, preferably olsalazine is used for treatment of prophylaxis of constipation.

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Excerpt(s): This application is a 371 of PCT/AU98/00332 filed May 7, 1998. This invention relates to methods and compositions for the treatment of bowel disorders characterised by constipation. Such disorders include segments of Irritable Bowel Syndrome (IBS) characterised by constipation, chronic pseudo-obstruction, chronic abdominal bloating syndrome and functional constipation. Symptoms include abdominal pain, constipation, bloating, acid reflux, flatulence, nausea and vomiting, chronic lethargy and sleep disorders. Constipation is a very common condition in the west, affecting about 20% of the population. Yet, to date no effective therapy is available. Chronic constipation is a condition largely confined to women and is of unknown etiology. Diet, psychology, motility disturbances and enteric nervous dysplasia have been identified as possible causes or factors. However, for the majority of patients the cause of constipation remains obscure. The pathogenesis of irritable bowel syndrome has also hitherto been unknown. Conventional treatments have been unsatisfactory as instanced by the very large number of therapies available and recommended from time to time. These have included psychotherapy, dietary regimens, and laxatives. To date, there is no evidence that any such therapies influence the underlying mechanism of the disorder and certainly cure is not possible. Web site: http://www.delphion.com/details?pn=US06426338__ •

Treatment of demyelinating diseases Inventor(s): Weinreb; Herman J. (New York, NY) Assignee(s): The Rockefeller University (New York, NY) Patent Number: 4,760,092 Date filed: December 3, 1986 Abstract: Method of treating demyelinating diseases such as multiple sclerosis by treatment with colchicine or colchiceine. Excerpt(s): This invention relates to the treatment of demyelirating diseases, particularly multiple sclerosis (MS), with colchicine or colchiceine. Demyelinating diseases of central or peripheral origin are diseases which destroy myelin which is a substance compounded principally of fats and proteins. It is wrapped in numerous thin layers around nerve fibers where it acts as an insulator and speeds the transmission of messages along the nerve fibers. These afflictions include for example MS, GuillainBarre syndrome and polymyositis. Of these, MS is by far the most prevalent. This invention will be described principally as it relates to MS. In the absence of a known cause for the disease, treatments have been empirical. The treatments can be divided principally into anti-inflammatory, immunosuppressive, anti-infective and biological response modifications. Additionally, a large number of miscellaneous treatments have been attempted. No satisfactory treatment of MS has yet been revealed. Web site: http://www.delphion.com/details?pn=US04760092__

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Tricyclic compounds Inventor(s): Brion; Francis (Gagny, FR), Chappert; Bernadette (Paris, FR), Diolez; Christian (Palaiseau, FR), Marie; Christian (Noisy le Sec, FR), Mazurie; Alain (Vaujours, FR), Middendorp; Michel (Faremoutiers, FR), Pronine; Didier (Rosny Sous Bois, FR), Toromanoff; Edmond (Paris, FR) Assignee(s): Roussel Uclaf (FR) Patent Number: 5,705,704 Date filed: March 1, 1996 Abstract: Novel tricyclic compounds of formula I as defined in the specification, a process for their preparation and their use for the preparation of optically active or racemic colchicine and thiocolchicine derivatives. Excerpt(s): It is an object of the invention to provide the novel compounds of formula I and a process of preparing the same. It is another object of the invention to provide a novel process for the preparation of the compounds of formula II. These and other objects and advantages of the invention will become obvious from the following detailed description. Web site: http://www.delphion.com/details?pn=US05705704__

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Use of colchicine for the control of retroviruses Inventor(s): Hall; William W. (New York, NY), Lyons; Michael (Irvington, NY), Read; Stanley E. (Toronto, CA), Zabriskie; John B. (New York, NY) Assignee(s): The Rockefeller University (New York, NY) Patent Number: 5,182,306 Date filed: August 12, 1991 Abstract: This invention relates to treating vetrovirus of the leutivirous group with colchicine. Excerpt(s): This invention is concerned with methods of treating humans infected with retroviruses of the lentivirus subgroup. Retroviruses are a well known class of viruses characterized by the presence of an RNA genome which is copied (transcribed) into DNA in the infected cell by an enzyme, reverse transcriptase (RT) which comes prepackaged in the infecting virus. Lentivirus is a subgroup of retrovirus characterized by the fact that the manifestation of infection in humans may take many years. The virus, after the initial invasion, may lie dormant for a long period of time, even several years, notably in the macrophages and then suddenly become activated when the right set of environmental circumstances is present. Several species of such lentivirus are known and recognized. These include, for example the human immunodeficiency viruses HIV-1 and HIV-2 responsible for the disease known as the Acquired Immune Deficiency Syndrome (AIDS) and HTLV the human T-cell lymphotropic virus which causes T-cell lymphomas, certain leukemias and tropical spastic paraparesis. This invention is applicable to these and other retroviruses having like activity. The viral replication cycle, i.e., the multiplication of the virus, or spread of the infection in the human system is through attachment to cell receptor of the T-cell (the T.sub.4 cell and macrophage in the case of an HIV virus), penetration of the cell outer membrane, uncoating of the retrovirus, transcription of viral RNA to DNA through the action of RT, integration of viral DNA into host chromosomes, and several other steps terminating

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with the generation of new virus particles containing RNA by known and understood mechanisms. Web site: http://www.delphion.com/details?pn=US05182306__

Patent Applications on Colchicine As of December 2000, U.S. patent applications are open to public viewing.9 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 colchicine: •

Antiproliferative colchicine compositions and uses thereof Inventor(s): Brown, Dennis M.; (Menlo Park, CA) Correspondence: Flehr Hohbach Test Albritton & Herbert Llp; Suite 3400; Four Embarcadero Center; San Francisco; CA; 94111-4187; US Patent Application Number: 20020123469 Date filed: October 31, 2001 Abstract: A method of treatment of a host with a cellular proliferative disease, including contacting the host with a colchicine family member and an antiproliferative agent, each in an amount sufficient to modulate said cellular proliferative disease, is described. In some embodiments, the colchicine family member is (S)-N-(5,6,7,9-tetrahydro-1,2,3,10tetrametho- xy-9-oxobenzo[a]heptalen-7-yl)acetamide. Antiproliferative agents of the invention include agents that interact with nucleic acids, for example, etoposide, camptothecin, and cisplatin. Antiproliferative agents of the invention also include agents that interact with tubulin targets, for example, paclitaxel and vinblastine. The invention also includes compositions containing a colchicine family member and an antiproliferative agent. Excerpt(s): This application claims the benefit of U.S. Provisional Application Nos. 60/244,765, 60/244,910, 60/244,911, 60/244,912, and 60/244,913, each filed on Oct. 31, 2000. The technical field of the invention is the use of colchicine family members with antiproliferative agents to treat a host with a cellular proliferative disease. Many classes of chemical compounds control microtubule assembly/disassembly by binding to tubulin. Virtually all of the observed therapeutic as well as toxic effects of the antimitotic drugs may be attributed to their actions on microtubule assembly and the subsequent microtubule-mediated processes. Web site: http://appft1.uspto.gov/netahtml/PTO/search-bool.html

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

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Estrogenic compounds as anti-mitotic agents Inventor(s): D'Amato, Robert John; (Lancaster, PA), Folkman, Moses Judah; (Brookline, MA) Correspondence: John S. Pratt, Esq; Kilpatrick Stockton, Llp; 1100 Peachtree Street; Suite 2800; Atlanta; GA; 30309; US Patent Application Number: 20020119959 Date filed: February 21, 2002 Abstract: The application discloses methods of treating mammalian diseases characterized by abnormal cell mitosis by administering estradiol derivatives including those comprising colchicine or combretastatin A-4 structural motifs of the general formulae found below in a dosage sufficient to inhibit cell mitosis. The application discloses novel compounds used in the methods. Excerpt(s): This invention relates to treating disease states characterized by abnormal cell mitosis. Cell mitosis is a multi-step process that includes cell division and replication (Alberts, B. et al. In The Cell, pp. 652 - 661 (1989); Stryer, E. Biochemistry (1988)). Mitosis is characterized by the intracellular movement and segregation of organelles, including mitotic spindles and chromosomes. Organelle movement and segregation are facilitated by the polymerization of the cell protein tubulin. Microtubules are formed from.alpha. and.beta. tubulin polymerization and the hydrolysis of GTP. Microtubule formation is important for cell mitosis, cell locomotion, and the movement of highly specialized cell structures such as cilia and flagella. Microtubules are extremely labile structures that are sensitive to a variety of chemically unrelated anti-mitotic drugs. For example, colchicine and nocadazole are anti-mitotic drugs that bind tubulin and inhibit tubulin polymerization (Stryer, E. Biochemistry (1988)). When used alone or in combination with other therapeutic drugs, colchicine may be used to treat cancer (WO-9303729-A, published Mar. 4, 1993; J 03240726-A, published Oct. 28, 1991), alter neuromuscular function, change blood pressure, increase sensitivity to compounds affecting sympathetic neuron function, depress respiration, and relieve gout (Physician's Desk Reference, Vol. 47, p. 1487, (1993)). 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 colchicine, 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 “colchicine” (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 colchicine. You can also use this procedure to view pending patent applications concerning colchicine. 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 6. BOOKS ON COLCHICINE Overview This chapter provides bibliographic book references relating to colchicine. In addition to online booksellers such as www.amazon.com and www.bn.com, excellent sources for book titles on colchicine 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 “colchicine” (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 colchicine: •

Primary Biliary Cirrhosis: From Pathogenesis to Clinical Treatment Source: Boston, MA: Kluwer Academic Publishers. 1998. 176 p. Contact: Available from Kluwer Academic Publishers. Customer Service Deparment, P.O. Box 358, Accord Station, Hingham, MA 02018-0358. (781) 871-6600. Fax (781) 6819045. E-mail: [email protected]. Website: www.wkap.nl. Summary: This monograph reprints papers from a conference held in November 1997 in Chicago, Illinois, on the clinical features (symptoms), pathogenesis, and treatment of primary biliary cirrhosis (PBC). PBC is generally considered to be an autoimmune disease and one that occurs in patients who are genetically predisposed to the disease. The part played by mitochondrial antibodies (AMA) in pathogenesis of PBC remains controversial. Alternatively, the disease may have an infectious etiology (cause). Therapy can be directed against any of these injurious processes. Drug therapy, notably combinations of drugs, can be used. Fibrosis (scarring) of the bile ducts occurs in PBC

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and is responsible for the end picture of cirrhosis (liver scarring). Complications such as ascites (fluid accumulation) and portal hypertension (high blood pressure) need to be treated; other complications can include bone thinning and pruritus (itching). Liver (hepatic) transplantation performed before the terminal stages of PBC offers a five year survival exceeding 85 percent. There is evidence of recurrence in the graft. The monograph includes 20 chapters covering the natural history and demography of PBC, the immune basis for PBC, isolation and cloning of antimitochondrial antibodies, determining pathogenesis, molecular considerations of PBC, animal models of PBC, fibrogenesis in PBC, natural history models, portal hypertension in patients with PBC, osteoporosis, managing fatigue in the patients with PBC, pruritus associated with cholestasis (suppression of the flow of bile), immunosuppressant agents, methotrexate and colchicine in the treatment of PBC, corticosteroids in PBC, ursodeoxycholic acid treatment of PBC, ursodiol and combination therapy, transplantation, and new clinical trials in PBC. Each chapter concludes with references and a subject index concludes the monograph.

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 “colchicine” (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:10 •

Effect of N-methylethylphenylbarbituric acid (Prominal) on the cholesterol content in the ovarian interstitial gland of the rat. The effect of colchicine on the increase in ovarian weight and phospholipids at gonadotrophic stimulation. Quantitative relati. Author: Claesson, Lennart; Year: 1954

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

10

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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Methotrexate and Colchicine in the Treatment of Primary Biliary Cirrhosis Source: in Lindor, K.D.; Heathcote, E.J.; Poupon, R., eds. Primary Biliary Cirrhosis: From Pathogenesis to Clinical Treatment. Boston, MA: Kluwer Academic Publishers. 1998. p. 124-129. Contact: Available from Kluwer Academic Publishers. Customer Service Deparment, P.O. Box 358, Accord Station, Hingham, MA 02018-0358. (781) 871-6600. Fax (781) 6819045. E-mail: [email protected]. Website: www.wkap.nl. Summary: Primary biliary cirrhosis (PBC) is a chronic cholestasic (lack of bile flow) liver disease of unknown etiology (cause), although the association with a large number of autoimmune disorders suggests that the disease may be of autoimmune origin. The disease usually affects middle aged women and progresses from asymptomatic disease with only laboratory abnormalities to a severe cholestatic disease with deep jaundice, xanthomas (fatty tumors in the skin), portal hypertension (high blood pressure), and eventually liver failure. This chapter on the use of methotrexate and colchicine to treat PBC is from a monograph that reprints papers from a conference held in November 1997 in Chicago, Illinois, on the clinical features (symptoms), pathogenesis, and treatment of PBC. Colchicine and methotrexate continue to be evaluated in the treatment of PBC. Although most prospective studies demonstrate that colchicine improves biochemical tests of liver function, albeit to a lesser degree than ursodiol, there is still no agreement concerning its effectiveness in this disease. The data on methotrexate are mixed; some studies suggest efficacy and others do not. Results of studies to determine whether either colchicine or methotrexate has any additive effect to that of ursodeoxycholic acid (UDCA) are also at variance. In the author's experience, both drugs have demonstrated efficacy when adequate doses are used. In addition, methotrexate has had additive effects to those of UDCA if given to patients who have responded incompletely or not at all to UDCA, and colchicine has been effective in a subgroup of patients who have responded incompletely to the combination of UDCA and methotrexate. The author stresses that there is no reason to give either drug to the patient who responds completely to UDCA. 35 references.

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CHAPTER 7. PERIODICALS AND NEWS ON COLCHICINE Overview In this chapter, we suggest a number of news sources and present various periodicals that cover colchicine.

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

Methotrexate superior to colchicine in patients with primary biliary cirrhosis Source: Reuters Medical News Date: November 25, 1999

•

Preliminary Study Finds Treatment With Colchicine Benefits Some Asthma Patients Source: Reuters Medical News Date: April 17, 1995

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

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Academic Periodicals covering Colchicine Numerous periodicals are currently indexed within the National Library of Medicine’s PubMed database that are known to publish articles relating to colchicine. In addition to these sources, you can search for articles covering colchicine 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 8. 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 colchicine. 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 colchicine. 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 colchicine: Probenecid and Colchicine •

Systemic - U.S. Brands: ColBenemid; Col-Probenecid; Proben-C http://www.nlm.nih.gov/medlineplus/druginfo/uspdi/202481.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. 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 Institute11: •

Office of the Director (OD); guidelines consolidated across agencies available at http://www.nih.gov/health/consumer/conkey.htm

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National Institute of General Medical Sciences (NIGMS); fact sheets available at http://www.nigms.nih.gov/news/facts/

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National Library of Medicine (NLM); extensive encyclopedia (A.D.A.M., Inc.) with guidelines: http://www.nlm.nih.gov/medlineplus/healthtopics.html

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National Cancer Institute (NCI); guidelines available at http://www.cancer.gov/cancerinfo/list.aspx?viewid=5f35036e-5497-4d86-8c2c714a9f7c8d25

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

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

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

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National Institute on Aging (NIA); guidelines available at http://www.nia.nih.gov/health/

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These publications are typically written by one or more of the various NIH Institutes.

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National Institute on Alcohol Abuse and Alcoholism (NIAAA); guidelines available at http://www.niaaa.nih.gov/publications/publications.htm

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National Institute of Allergy and Infectious Diseases (NIAID); guidelines available at http://www.niaid.nih.gov/publications/

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National Institute of Arthritis and Musculoskeletal and Skin Diseases (NIAMS); fact sheets and guidelines available at http://www.niams.nih.gov/hi/index.htm

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National Institute of Child Health and Human Development (NICHD); guidelines available at http://www.nichd.nih.gov/publications/pubskey.cfm

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National Institute on Deafness and Other Communication Disorders (NIDCD); fact sheets and guidelines at http://www.nidcd.nih.gov/health/

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National Institute of Dental and Craniofacial Research (NIDCR); guidelines available at http://www.nidr.nih.gov/health/

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National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK); guidelines available at http://www.niddk.nih.gov/health/health.htm

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National Institute on Drug Abuse (NIDA); guidelines available at http://www.nida.nih.gov/DrugAbuse.html

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National Institute of Environmental Health Sciences (NIEHS); environmental health information available at http://www.niehs.nih.gov/external/facts.htm

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National Institute of Mental Health (NIMH); guidelines available at http://www.nimh.nih.gov/practitioners/index.cfm

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National Institute of Neurological Disorders and Stroke (NINDS); neurological disorder information pages available at http://www.ninds.nih.gov/health_and_medical/disorder_index.htm

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National Institute of Nursing Research (NINR); publications on selected illnesses at http://www.nih.gov/ninr/news-info/publications.html

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National Institute of Biomedical Imaging and Bioengineering; general information at http://grants.nih.gov/grants/becon/becon_info.htm

•

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.12 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:13 •

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

12

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). 13 See http://www.nlm.nih.gov/databases/databases.html.

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•

Toxicology and Environmental Health Information (TOXNET): Databases covering toxicology and environmental health: http://sis.nlm.nih.gov/Tox/ToxMain.html

•

Visible Human Interface: Anatomically detailed, three-dimensional representations of normal male and female human bodies: http://www.nlm.nih.gov/research/visible/visible_human.html

The NLM Gateway14 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.15 To use the NLM Gateway, simply go to the search site at http://gateway.nlm.nih.gov/gw/Cmd. Type “colchicine” (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 17136 74 962 8 69 18249

HSTAT16 HSTAT is a free, Web-based resource that provides access to full-text documents used in healthcare decision-making.17 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.18 Simply search by “colchicine” (or synonyms) at the following Web site: http://text.nlm.nih.gov.

14

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

15

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). 16 Adapted from HSTAT: http://www.nlm.nih.gov/pubs/factsheets/hstat.html. 17 18

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

Other important documents in HSTAT include: the National Institutes of Health (NIH) Consensus Conference Reports and Technology Assessment Reports; the HIV/AIDS Treatment Information Service (ATIS) resource documents; the Substance Abuse and Mental Health Services Administration's Center for Substance Abuse Treatment (SAMHSA/CSAT) Treatment Improvement Protocols (TIP) and Center for Substance Abuse Prevention (SAMHSA/CSAP) Prevention Enhancement Protocols System (PEPS); the Public Health Service (PHS) Preventive Services Task Force's Guide to Clinical Preventive Services; the independent, nonfederal Task Force on Community Services’ Guide to Community Preventive Services; and the Health Technology Advisory Committee (HTAC) of the Minnesota Health Care Commission (MHCC) health technology evaluations.

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Coffee Break: Tutorials for Biologists19 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.20 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.21 This site has new articles every few weeks, so it can be considered an online magazine of sorts. It is intended for general background information. You can access the Coffee Break Web site at the following hyperlink: http://www.ncbi.nlm.nih.gov/Coffeebreak/.

Other Commercial Databases In addition to resources maintained by official agencies, other databases exist that are commercial ventures addressing medical professionals. Here are some examples that may interest you: •

CliniWeb International: Index and table of contents to selected clinical information on the Internet; see http://www.ohsu.edu/cliniweb/.

•

Medical World Search: Searches full text from thousands of selected medical sites on the Internet; see http://www.mwsearch.com/.

19 Adapted 20

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. 21 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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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 colchicine 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 colchicine. 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 colchicine. 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 “colchicine”:

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Arthritis http://www.nlm.nih.gov/medlineplus/arthritis.html Behcet's Syndrome http://www.nlm.nih.gov/medlineplus/behcetssyndrome.html Fibromyalgia http://www.nlm.nih.gov/medlineplus/fibromyalgia.html Gout and Pseudogout http://www.nlm.nih.gov/medlineplus/goutandpseudogout.html Osteoarthritis http://www.nlm.nih.gov/medlineplus/osteoarthritis.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 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 colchicine. 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: •

AOL: http://search.aol.com/cat.adp?id=168&layer=&from=subcats

•

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

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Finding Associations There are several Internet directories that provide lists of medical associations with information on or resources relating to colchicine. By consulting all of associations listed in this chapter, you will have nearly exhausted all sources for patient associations concerned with colchicine. 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 colchicine. 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 “colchicine” (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 “colchicine”. 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 “colchicine” (or synonyms) into the “For these words:” box. You should check back periodically with this database since it is updated every three months.

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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 “colchicine” (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.22

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

22

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

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libraries recommended by the National Library of Medicine (sorted alphabetically by name of the U.S. state or Canadian province where the library is located)23: •

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/

23

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

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•

Connecticut: Waterbury Hospital Health Center Library (Waterbury Hospital, Waterbury), http://www.waterburyhospital.com/library/consumer.shtml

•

Delaware: Consumer Health Library (Christiana Care Health System, Eugene du Pont Preventive Medicine & Rehabilitation Institute, Wilmington), http://www.christianacare.org/health_guide/health_guide_pmri_health_info.cfm

•

Delaware: Lewis B. Flinn Library (Delaware Academy of Medicine, Wilmington), http://www.delamed.org/chls.html

•

Georgia: Family Resource Library (Medical College of Georgia, Augusta), http://cmc.mcg.edu/kids_families/fam_resources/fam_res_lib/frl.htm

•

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/

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•

Manitoba, Canada: Consumer & Patient Health Information Service (University of Manitoba Libraries), http://www.umanitoba.ca/libraries/units/health/reference/chis.html

•

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/

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•

Nevada: Health Science Library, West Charleston Library (Las Vegas-Clark County Library District, Las Vegas), http://www.lvccld.org/special_collections/medical/index.htm

•

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/

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•

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

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ONLINE GLOSSARIES The Internet provides access to a number of free-to-use medical dictionaries. The National Library of Medicine has compiled the following list of online dictionaries: •

ADAM Medical Encyclopedia (A.D.A.M., Inc.), comprehensive medical reference: http://www.nlm.nih.gov/medlineplus/encyclopedia.html

•

MedicineNet.com Medical Dictionary (MedicineNet, Inc.): http://www.medterms.com/Script/Main/hp.asp

•

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).

Online Dictionary Directories The following are additional online directories compiled by the National Library of Medicine, including a number of specialized medical dictionaries: •

Medical Dictionaries: Medical & Biological (World Health Organization): http://www.who.int/hlt/virtuallibrary/English/diction.htm#Medical

•

MEL-Michigan Electronic Library List of Online Health and Medical Dictionaries (Michigan Electronic Library): http://mel.lib.mi.us/health/health-dictionaries.html

•

Patient Education: Glossaries (DMOZ Open Directory Project): http://dmoz.org/Health/Education/Patient_Education/Glossaries/

•

Web of Online Dictionaries (Bucknell University): http://www.yourdictionary.com/diction5.html#medicine

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COLCHICINE DICTIONARY The definitions below are derived from official public sources, including the National Institutes of Health [NIH] and the European Union [EU]. Abdomen: That portion of the body that lies between the thorax and the pelvis. [NIH] Abdominal: Having to do with the abdomen, which is the part of the body between the chest and the hips that contains the pancreas, stomach, intestines, liver, gallbladder, and other organs. [NIH] Abdominal Pain: Sensation of discomfort, distress, or agony in the abdominal region. [NIH] 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] Acetaldehyde: A colorless, flammable liquid used in the manufacture of acetic acid, perfumes, and flavors. It is also an intermediate in the metabolism of alcohol. It has a general narcotic action and also causes irritation of mucous membranes. Large doses may cause death from respiratory paralysis. [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] Acidosis: A pathologic condition resulting from accumulation of acid or depletion of the alkaline reserve (bicarbonate content) in the blood and body tissues, and characterized by an increase in hydrogen ion concentration. [EU] Acne: A disorder of the skin marked by inflammation of oil glands and hair glands. [NIH] Acne Vulgaris: A chronic disorder of the pilosebaceous apparatus associated with an increase in sebum secretion. It is characterized by open comedones (blackheads), closed comedones (whiteheads), and pustular nodules. The cause is unknown, but heredity and age are predisposing factors. [NIH] Acrylamide: A colorless, odorless, highly water soluble vinyl monomer formed from the hydration of acrylonitrile. It is primarily used in research laboratories for electrophoresis, chromatography, and electron microscopy and in the sewage and wastewater treatment industries. [NIH] Acrylonitrile: A highly poisonous compound used widely in the manufacture of plastics, adhesives and synthetic rubber. [NIH] Adaptability: Ability to develop some form of tolerance to conditions extremely different from those under which a living organism evolved. [NIH] Adenine: A purine base and a fundamental unit of adenine nucleotides. [NIH] Adenocarcinoma: A malignant epithelial tumor with a glandular organization. [NIH] Adenoma: A benign epithelial tumor with a glandular organization. [NIH]

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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] 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] 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] Afferent: Concerned with the transmission of neural impulse toward the central part of the nervous system. [NIH] Affinity: 1. Inherent likeness or relationship. 2. A special attraction for a specific element, organ, or structure. 3. Chemical affinity; the force that binds atoms in molecules; the tendency of substances to combine by chemical reaction. 4. The strength of noncovalent chemical binding between two substances as measured by the dissociation constant of the complex. 5. In immunology, a thermodynamic expression of the strength of interaction between a single antigen-binding site and a single antigenic determinant (and thus of the stereochemical compatibility between them), most accurately applied to interactions among simple, uniform antigenic determinants such as haptens. Expressed as the association constant (K litres mole -1), which, owing to the heterogeneity of affinities in a population of antibody molecules of a given specificity, actually represents an average value (mean intrinsic association constant). 6. The reciprocal of the dissociation constant. [EU] 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] Albuterol: A racemic mixture with a 1:1 ratio of the r-isomer, levalbuterol, and s-albuterol. It is a short-acting beta 2-adrenergic agonist with its main clinical use in asthma. [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]

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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] Allergic Rhinitis: Inflammation of the nasal mucous membrane associated with hay fever; fits may be provoked by substances in the working environment. [NIH] Allopurinol: A xanthine oxidase inhibitor that decreases uric acid production. [NIH] Alopecia: Absence of hair from areas where it is normally present. [NIH] Alternative medicine: Practices not generally recognized by the medical community as standard or conventional medical approaches and used instead of standard treatments. Alternative medicine includes the taking of dietary supplements, megadose vitamins, and herbal preparations; the drinking of special teas; and practices such as massage therapy, magnet therapy, spiritual healing, and meditation. [NIH] Alum: A type of immune adjuvant (a substance used to help boost the immune response to a vaccine). Also called aluminum sulfate. [NIH] Amine: An organic compound containing nitrogen; any member of a group of chemical compounds formed from ammonia by replacement of one or more of the hydrogen atoms by organic (hydrocarbon) radicals. The amines are distinguished as primary, secondary, and tertiary, according to whether one, two, or three hydrogen atoms are replaced. The amines include allylamine, amylamine, ethylamine, methylamine, phenylamine, propylamine, and many other compounds. [EU] Amino Acid Sequence: The order of amino acids as they occur in a polypeptide chain. This is referred to as the primary structure of proteins. It is of fundamental importance in determining protein conformation. [NIH] Amino 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] Amnesia: Lack or loss of memory; inability to remember past experiences. [EU] Amphetamines: Analogs or derivatives of amphetamine. Many are sympathomimetics and central nervous system stimulators causing excitation, vasopression, bronchodilation, and to varying degrees, anorexia, analepsis, nasal decongestion, and some smooth muscle relaxation. [NIH] Ampulla: A sac-like enlargement of a canal or duct. [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] Amyloidosis: A group of diseases in which protein is deposited in specific organs (localized amyloidosis) or throughout the body (systemic amyloidosis). Amyloidosis may be either primary (with no known cause) or secondary (caused by another disease, including some

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types of cancer). Generally, primary amyloidosis affects the nerves, skin, tongue, joints, heart, and liver; secondary amyloidosis often affects the spleen, kidneys, liver, and adrenal glands. [NIH] 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] Anal: Having to do with the anus, which is the posterior opening of the large bowel. [NIH] 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] 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] 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 unconscious state is achieved, or may act locally to induce numbness or lack of sensation at a targeted site. [NIH] Aneuploidy: The chromosomal constitution of cells which deviate from the normal by the addition or subtraction of chromosomes or chromosome pairs. In a normally diploid cell the loss of a chromosome pair is termed nullisomy (symbol: 2N-2), the loss of a single chromosome is monosomy (symbol: 2N-1), the addition of a chromosome pair is tetrasomy (symbol: 2N+2), the addition of a single chromosome is trisomy (symbol: 2N+1). [NIH] Angioplasty: Endovascular reconstruction of an artery, which may include the removal of atheromatous plaque and/or the endothelial lining as well as simple dilatation. These are procedures performed by catheterization. When reconstruction of an artery is performed surgically, it is called endarterectomy. [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]

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Anionic: Pertaining to or containing an anion. [EU] Anions: Negatively charged atoms, radicals or groups of atoms which travel to the anode or positive pole during electrolysis. [NIH] Anisotropy: A physical property showing different values in relation to the direction in or along which the measurement is made. The physical property may be with regard to thermal or electric conductivity or light refraction. In crystallography, it describes crystals whose index of refraction varies with the direction of the incident light. It is also called acolotropy and colotropy. The opposite of anisotropy is isotropy wherein the same values characterize the object when measured along axes in all directions. [NIH] Anode: Electrode held at a positive potential with respect to a cathode. [NIH] Anterograde: Moving or extending forward; called also antegrade. [EU] Antiallergic: Counteracting allergy or allergic conditions. [EU] Antibacterial: A substance that destroys bacteria or suppresses their growth or reproduction. [EU] Antibiotic: A drug used to treat infections caused by bacteria and other microorganisms. [NIH]

Antibodies: Immunoglobulin molecules having a specific amino acid sequence by virtue of which they interact only with the antigen that induced their synthesis in cells of the lymphoid series (especially plasma cells), or with an antigen closely related to it. [NIH] Antibody: A type of protein made by certain white blood cells in response to a foreign substance (antigen). Each antibody can bind to only a specific antigen. The purpose of this binding is to help destroy the antigen. Antibodies can work in several ways, depending on the nature of the antigen. Some antibodies destroy antigens directly. Others make it easier for white blood cells to destroy the antigen. [NIH] Antibody-Dependent Cell Cytotoxicity: The phenomenon of antibody-mediated target cell destruction by non-sensitized effector cells. The identity of the target cell varies, but it must possess surface IgG whose Fc portion is intact. The effector cell is a "killer" cell possessing Fc receptors. It may be a lymphocyte lacking conventional B- or T-cell markers, or a monocyte, macrophage, or polynuclear leukocyte, depending on the identity of the target cell. The reaction is complement-independent. [NIH] Anticholinergic: An agent that blocks the parasympathetic nerves. Called also parasympatholytic. [EU] Anticoagulant: A drug that helps prevent blood clots from forming. Also called a blood thinner. [NIH] Anticonvulsants: Drugs used to prevent seizures or reduce their severity. [NIH] Antidiuretic: Suppressing the rate of urine formation. [EU] Antifungal: Destructive to fungi, or suppressing their reproduction or growth; effective against fungal infections. [EU] Antigen: Any substance which is capable, under appropriate conditions, of inducing a specific immune response and of reacting with the products of that response, that is, with specific antibody or specifically sensitized T-lymphocytes, or both. Antigens may be soluble substances, such as toxins and foreign proteins, or particulate, such as bacteria and tissue cells; however, only the portion of the protein or polysaccharide molecule known as the antigenic determinant (q.v.) combines with antibody or a specific receptor on a lymphocyte. Abbreviated Ag. [EU] Antigen-Antibody Complex: The complex formed by the binding of antigen and antibody

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molecules. The deposition of large antigen-antibody complexes leading to tissue damage causes immune complex diseases. [NIH] Anti-infective: An agent that so acts. [EU] Anti-inflammatory: Having to do with reducing inflammation. [NIH] 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] Antimitotic: Inhibiting or preventing mitosis. [EU] Antineoplastic: Inhibiting or preventing the development of neoplasms, checking the maturation and proliferation of malignant cells. [EU] Antineoplastic Agents: Substances that inhibit or prevent the proliferation of neoplasms. [NIH]

Antioxidant: A substance that prevents damage caused by free radicals. Free radicals are highly reactive chemicals that often contain oxygen. They are produced when molecules are split to give products that have unpaired electrons. This process is called oxidation. [NIH] Antiphlogistic: An agent that counteracts inflammation and fever. [EU] Antiproliferative: Counteracting a process of proliferation. [EU] Antispasmodic: An agent that relieves spasm. [EU] Antitubercular Agents: Drugs used in the treatment of tuberculosis. They are divided into two main classes: "first-line" agents, those with the greatest efficacy and acceptable degrees of toxicity used successfully in the great majority of cases; and "second-line" drugs used in drug-resistant cases or those in which some other patient-related condition has compromised the effectiveness of primary therapy. [NIH] Antiviral: Destroying viruses or suppressing their replication. [EU] Anus: The opening of the rectum to the outside of the body. [NIH] Aphthous Stomatitis: Inflammation of the mucous membrane of the mouth. [NIH] Aplasia: Lack of development of an organ or tissue, or of the cellular products from an organ or tissue. [EU] Apolipoproteins: The protein components of lipoproteins which remain after the lipids to which the proteins are bound have been removed. They play an important role in lipid transport and metabolism. [NIH] Aponeurosis: Tendinous expansion consisting of a fibrous or membranous sheath which serves as a fascia to enclose or bind a group of muscles. [NIH] Apoptosis: One of the two mechanisms by which cell death occurs (the other being the pathological process of necrosis). Apoptosis is the mechanism responsible for the physiological deletion of cells and appears to be intrinsically programmed. It is characterized by distinctive morphologic changes in the nucleus and cytoplasm, chromatin cleavage at regularly spaced sites, and the endonucleolytic cleavage of genomic DNA (DNA fragmentation) at internucleosomal sites. This mode of cell death serves as a balance to mitosis in regulating the size of animal tissues and in mediating pathologic processes associated with tumor growth. [NIH] Aqueous: Having to do with water. [NIH] Arachidonic Acid: An unsaturated, essential fatty acid. It is found in animal and human fat as well as in the liver, brain, and glandular organs, and is a constituent of animal

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phosphatides. It is formed by the synthesis from dietary linoleic acid and is a precursor in the biosynthesis of prostaglandins, thromboxanes, and leukotrienes. [NIH] Arterial: Pertaining to an artery or to the arteries. [EU] Arteries: The vessels carrying blood away from the heart. [NIH] Arterioles: The smallest divisions of the arteries located between the muscular arteries and the capillaries. [NIH] Artery: Vessel-carrying blood from the heart to various parts of the body. [NIH] Articular: Of or pertaining to a joint. [EU] Asbestos: Fibrous incombustible mineral composed of magnesium and calcium silicates with or without other elements. It is relatively inert chemically and used in thermal insulation and fireproofing. Inhalation of dust causes asbestosis and later lung and gastrointestinal neoplasms. [NIH] Asbestosis: A lung disorder caused by constant inhalation of asbestos particles. [NIH] Ascites: Accumulation or retention of free fluid within the peritoneal cavity. [NIH] Ascorbic Acid: A six carbon compound related to glucose. It is found naturally in citrus fruits and many vegetables. Ascorbic acid is an essential nutrient in human diets, and necessary to maintain connective tissue and bone. Its biologically active form, vitamin C, functions as a reducing agent and coenzyme in several metabolic pathways. Vitamin C is considered an antioxidant. [NIH] Aspartate: A synthetic amino acid. [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] 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 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] Asymptomatic: Having no signs or symptoms of disease. [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] Autoimmune disease: A condition in which the body recognizes its own tissues as foreign and directs an immune response against them. [NIH] 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

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afferents; these and related central and sensory structures are sometimes (but not here) considered to be part of the autonomic nervous system itself. [NIH] Axilla: The underarm or armpit. [NIH] Axons: Nerve fibers that are capable of rapidly conducting impulses away from the neuron cell body. [NIH] Back Pain: Acute or chronic pain located in the posterior regions of the trunk, including the thoracic, lumbar, sacral, or adjacent regions. [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] Bactericidal: Substance lethal to bacteria; substance capable of killing bacteria. [NIH] Barbiturate: A drug with sedative and hypnotic effects. Barbiturates have been used as sedatives and anesthetics, and they have been used to treat the convulsions associated with epilepsy. [NIH] Basal cell carcinoma: A type of skin cancer that arises from the basal cells, small round cells found in the lower part (or base) of the epidermis, the outer layer of the skin. [NIH] Basal cells: Small, round cells found in the lower part (or base) of the epidermis, the outer layer of the skin. [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] Basophil: A type of white blood cell. Basophils are granulocytes. [NIH] Benign: Not cancerous; does not invade nearby tissue or spread to other parts of the body. [NIH]

Benomyl: A systemic agricultural fungicide used for control of certain fungal diseases of stone fruit. [NIH] Beta-Galactosidase: A group of enzymes that catalyzes the hydrolysis of terminal, nonreducing beta-D-galactose residues in beta-galactosides. Deficiency of beta-Galactosidase A1 may cause gangliodisosis GM1. EC 3.2.1.23. [NIH] Beta-pleated: Particular three-dimensional pattern of amyloidoses. [NIH] Bilateral: Affecting both the right and left side of body. [NIH] Bile: An emulsifying agent produced in the liver and secreted into the duodenum. Its composition includes bile acids and salts, cholesterol, and electrolytes. It aids digestion of fats in the duodenum. [NIH] Bile Acids: Acids made by the liver that work with bile to break down fats. [NIH] Bile Acids and Salts: Steroid acids and salts. The primary bile acids are derived from cholesterol in the liver and usually conjugated with glycine or taurine. The secondary bile acids are further modified by bacteria in the intestine. They play an important role in the digestion and absorption of fat. They have also been used pharmacologically, especially in the treatment of gallstones. [NIH] Bile duct: A tube through which bile passes in and out of the liver. [NIH]

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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] Binding agent: A substance that makes a loose mixture stick together. For example, binding agents can be used to make solid pills from loose powders. [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] Biochemical: Relating to biochemistry; characterized by, produced by, or involving chemical reactions in living organisms. [EU] Biogenesis: The origin of life. It includes studies of the potential basis for life in organic compounds but excludes studies of the development of altered forms of life through mutation and natural selection, which is evolution. [NIH] Biological response modifier: BRM. A substance that stimulates the body's response to infection and disease. [NIH] Biological therapy: Treatment to stimulate or restore the ability of the immune system to fight infection and disease. Also used to lessen side effects that may be caused by some cancer treatments. Also known as immunotherapy, biotherapy, or biological response modifier (BRM) therapy. [NIH] Biological Transport: The movement of materials (including biochemical substances and drugs) across cell membranes and epithelial layers, usually by passive diffusion. [NIH] Biomarkers: Substances sometimes found in an increased amount in the blood, other body fluids, or tissues and that may suggest the presence of some types of cancer. Biomarkers include CA 125 (ovarian cancer), CA 15-3 (breast cancer), CEA (ovarian, lung, breast, pancreas, and GI tract cancers), and PSA (prostate cancer). Also called tumor markers. [NIH] 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] Biotin: Hexahydro-2-oxo-1H-thieno(3,4-d)imidazole-4-pentanoic acid. Growth factor present in minute amounts in every living cell. It occurs mainly bound to proteins or polypeptides and is abundant in liver, kidney, pancreas, yeast, and milk.The biotin content of cancerous tissue is higher than that of normal tissue. [NIH] 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 non-

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synthetic (oxidation-reduction, hydrolysis) or synthetic (glucuronide formation, sulfate conjugation, acetylation, methylation). This also includes metabolic detoxication and clearance. [NIH] Bivalent: Pertaining to a group of 2 homologous or partly homologous chromosomes during the zygotene stage of prophase to the first metaphase in meiosis. [NIH] Bladder: The organ that stores urine. [NIH] Blister: Visible accumulations of fluid within or beneath the epidermis. [NIH] Bloating: Fullness or swelling in the abdomen that often occurs after meals. [NIH] Blood Coagulation: The process of the interaction of blood coagulation factors that results in an insoluble fibrin clot. [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] Body Fluids: Liquid components of living organisms. [NIH] Bone Marrow: The soft tissue filling the cavities of bones. Bone marrow exists in two types, yellow and red. Yellow marrow is found in the large cavities of large bones and consists mostly of fat cells and a few primitive blood cells. Red marrow is a hematopoietic tissue and is the site of production of erythrocytes and granular leukocytes. Bone marrow is made up of a framework of connective tissue containing branching fibers with the frame being filled with marrow cells. [NIH] 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] 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] Brachytherapy: A collective term for interstitial, intracavity, and surface radiotherapy. It uses small sealed or partly-sealed sources that may be placed on or near the body surface or within a natural body cavity or implanted directly into the tissues. [NIH] Brain Hypoxia: Lack of oxygen leading to unconsciousness. [NIH] Brain Infarction: The formation of an area of necrosis in the brain, including the cerebral hemispheres (cerebral infarction), thalami, basal ganglia, brain stem (brain stem infarctions), or cerebellum secondary to an insufficiency of arterial or venous blood flow. [NIH] Brain Ischemia: Localized reduction of blood flow to brain tissue due to arterial obtruction or systemic hypoperfusion. This frequently occurs in conjuction with brain hypoxia. Prolonged ischemia is associated with brain infarction. [NIH] Breeding: The science or art of changing the constitution of a population of plants or animals through sexual reproduction. [NIH] Broad-spectrum: Effective against a wide range of microorganisms; said of an antibiotic. [EU]

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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] Bronchoconstriction: Diminution of the caliber of a bronchus physiologically or as a result of pharmacological intervention. [NIH] Bullous: Pertaining to or characterized by bullae. [EU] Bupivacaine: A widely used local anesthetic agent. [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] Calculi: An abnormal concretion occurring mostly in the urinary and biliary tracts, usually composed of mineral salts. Also called stones. [NIH] Callus: A callosity or hard, thick skin; the bone-like reparative substance that is formed round the edges and fragments of broken bone. [NIH] Camptothecin: An alkaloid isolated from the stem wood of the Chinese tree, Camptotheca acuminata. This compound selectively inhibits the nuclear enzyme DNA topoisomerase. Several semisynthetic analogs of camptothecin have demonstrated antitumor activity. [NIH] Capillary: Any one of the minute vessels that connect the arterioles and venules, forming a network in nearly all parts of the body. Their walls act as semipermeable membranes for the interchange of various substances, including fluids, between the blood and tissue fluid; called also vas capillare. [EU] Capsaicin: Cytotoxic alkaloid from various species of Capsicum (pepper, paprika), of the Solanaceae. [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] Carcinogenic: Producing carcinoma. [EU] Carcinoma: Cancer that begins in the skin or in tissues that line or cover internal organs. [NIH]

Cardiac: Having to do with the heart. [NIH] Cardiomyopathy: A general diagnostic term designating primary myocardial disease, often of obscure or unknown etiology. [EU] Cardiovascular: Having to do with the heart and blood vessels. [NIH] Cardiovascular System: The heart and the blood vessels by which blood is pumped and circulated through the body. [NIH]

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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] 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] Catheterization: Use or insertion of a tubular device into a duct, blood vessel, hollow organ, or body cavity for injecting or withdrawing fluids for diagnostic or therapeutic purposes. It differs from intubation in that the tube here is used to restore or maintain patency in obstructions. [NIH] Cations: Postively charged atoms, radicals or groups of atoms which travel to the cathode or negative pole during electrolysis. [NIH] Cause of Death: Factors which produce cessation of all vital bodily functions. They can be analyzed from an epidemiologic viewpoint. [NIH] Cell: The individual unit that makes up all of the tissues of the body. All living things are made up of one or more cells. [NIH] Cell Cycle: The complex series of phenomena, occurring between the end of one cell division and the end of the next, by which cellular material is divided between daughter cells. [NIH] Cell Death: The termination of the cell's ability to carry out vital functions such as metabolism, growth, reproduction, responsiveness, and adaptability. [NIH] Cell Differentiation: Progressive restriction of the developmental potential and increasing specialization of function which takes place during the development of the embryo and leads to the formation of specialized cells, tissues, and organs. [NIH] 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 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 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] Central Nervous System: The main information-processing organs of the nervous system, consisting of the brain, spinal cord, and meninges. [NIH] Centromere: The clear constricted portion of the chromosome at which the chromatids are joined and by which the chromosome is attached to the spindle during cell division. [NIH] 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

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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] 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] Chemotactic Factors: Chemical substances that attract or repel cells or organisms. The concept denotes especially those factors released as a result of tissue injury, invasion, or immunologic activity, that attract leukocytes, macrophages, or other cells to the site of infection or insult. [NIH] Chemotaxis: The movement of cells or organisms toward or away from a substance in response to its concentration gradient. [NIH] Chemotherapeutic agent: A drug used to treat cancer. [NIH] Chemotherapy: Treatment with anticancer drugs. [NIH] Chenodeoxycholic Acid: A bile acid, usually conjugated with either glycine or taurine. It acts as a detergent to solubilize fats for intestinal absorption and is reabsorbed by the small intestine. It is used as cholagogue, a choleretic laxative, and to prevent or dissolve gallstones. [NIH] Chlorine: A greenish-yellow, diatomic gas that is a member of the halogen family of elements. It has the atomic symbol Cl, atomic number 17, and atomic weight 70.906. It is a powerful irritant that can cause fatal pulmonary edema. Chlorine is used in manufacturing, as a reagent in synthetic chemistry, for water purification, and in the production of chlorinated lime, which is used in fabric bleaching. [NIH] Chloroquine: The prototypical antimalarial agent with a mechanism that is not well understood. It has also been used to treat rheumatoid arthritis, systemic lupus erythematosus, and in the systemic therapy of amebic liver abscesses. [NIH] Cholangitis: Inflammation of a bile duct. [NIH] Cholecystokinin: A 33-amino acid peptide secreted by the upper intestinal mucosa and also found in the central nervous system. It causes gallbladder contraction, release of pancreatic exocrine (or digestive) enzymes, and affects other gastrointestinal functions. Cholecystokinin may be the mediator of satiety. [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] Choleretic: A choleretic agent. [EU] Cholestasis: Impairment of biliary flow at any level from the hepatocyte to Vater's ampulla. [NIH]

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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] Chorion: The outermost extraembryonic membrane. [NIH] Chorionic Villi: The threadlike, vascular projections of the chorion which enter into the formation of the placenta. [NIH] Chromatin: The material of chromosomes. It is a complex of DNA, histones, and nonhistone proteins (chromosomal proteins, non-histone) found within the nucleus of a cell. [NIH] Chromosomal: Pertaining to chromosomes. [EU] Chromosome: Part of a cell that contains genetic information. Except for sperm and eggs, all human cells contain 46 chromosomes. [NIH] Chromosome Segregation: The orderly segregation of chromosomes during meiosis or mitosis. [NIH] Chronic: A disease or condition that persists or progresses over a long period of time. [NIH] Chronic Disease: Disease or ailment of long duration. [NIH] Chronic renal: Slow and progressive loss of kidney function over several years, often resulting in end-stage renal disease. People with end-stage renal disease need dialysis or transplantation to replace the work of the kidneys. [NIH] Circadian: Repeated more or less daily, i. e. on a 23- to 25-hour cycle. [NIH] Circadian Rhythm: The regular recurrence, in cycles of about 24 hours, of biological processes or activities, such as sensitivity to drugs and stimuli, hormone secretion, sleeping, feeding, etc. This rhythm seems to be set by a 'biological clock' which seems to be set by recurring daylight and darkness. [NIH] Cirrhosis: A type of chronic, progressive liver disease. [NIH] CIS: Cancer Information Service. The CIS is the National Cancer Institute's link to the public, interpreting and explaining research findings in a clear and understandable manner, and providing personalized responses to specific questions about cancer. Access the CIS by calling 1-800-4-CANCER, or by using the Web site at http://cis.nci.nih.gov. [NIH] Cisplatin: An inorganic and water-soluble platinum complex. After undergoing hydrolysis, it reacts with DNA to produce both intra and interstrand crosslinks. These crosslinks appear to impair replication and transcription of DNA. The cytotoxicity of cisplatin correlates with cellular arrest in the G2 phase of the cell cycle. [NIH] Clarithromycin: A semisynthetic macrolide antibiotic derived from erythromycin that is active against a variety of microorganisms. It can inhibit protein synthesis in bacteria by reversibly binding to the 50S ribosomal subunits. This inhibits the translocation of aminoacyl transfer-RNA and prevents peptide chain elongation. [NIH] Clinical Medicine: The study and practice of medicine by direct examination of the patient. [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] 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] Clubbing: A proliferative change in the soft tissues about the terminal phalanges of the fingers or toes, with no constant osseous changes. [NIH]

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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] Coenzyme: An organic nonprotein molecule, frequently a phosphorylated derivative of a water-soluble vitamin, that binds with the protein molecule (apoenzyme) to form the active enzyme (holoenzyme). [EU] Cofactor: A substance, microorganism or environmental factor that activates or enhances the action of another entity such as a disease-causing agent. [NIH] 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] Colon: The long, coiled, tubelike organ that removes water from digested food. The remaining material, solid waste called stool, moves through the colon to the rectum and leaves the body through the anus. [NIH] Colony-Stimulating Factors: Glycoproteins found in a subfraction of normal mammalian plasma and urine. They stimulate the proliferation of bone marrow cells in agar cultures and the formation of colonies of granulocytes and/or macrophages. The factors include interleukin-3 (IL-3), granulocyte colony-stimulating factor (G-CSF), macrophage colonystimulating factor (M-CSF), and granulocyte-macrophage colony-stimulating factor (GMCSF). [NIH] Combination Therapy: Association of 3 drugs to treat AIDS (AZT + DDC or DDI + protease inhibitor). [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,

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IgG3; C1q binds to a single IgM molecule or two adjacent IgG molecules. The alternative pathway can be activated by IgA immune complexes and also by nonimmunologic materials including bacterial endotoxins, microbial polysaccharides, and cell walls. Activation of the classic pathway triggers an enzymatic cascade involving C1, C4, C2 and C3; activation of the alternative pathway triggers a cascade involving C3 and factors B, D and P. Both result in the cleavage of C5 and the formation of the membrane attack complex. Complement activation also results in the formation of many biologically active complement fragments that act as anaphylatoxins, opsonins, or chemotactic factors. [EU] Complementary and alternative medicine: CAM. Forms of treatment that are used in addition to (complementary) or instead of (alternative) standard treatments. These practices are not considered standard medical approaches. CAM includes dietary supplements, megadose vitamins, herbal preparations, special teas, massage therapy, magnet therapy, spiritual healing, and meditation. [NIH] Complementary medicine: Practices not generally recognized by the medical community as standard or conventional medical approaches and used to enhance or complement the standard treatments. Complementary medicine includes the taking of dietary supplements, megadose vitamins, and herbal preparations; the drinking of special teas; and practices such as massage therapy, magnet therapy, spiritual healing, and meditation. [NIH] 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] Concentric: Having a common center of curvature or symmetry. [NIH] 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] Congestion: Excessive or abnormal accumulation of blood in a part. [EU] Conjugated: Acting or operating as if joined; simultaneous. [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] Consolidation: The healing process of a bone fracture. [NIH] Constipation: Infrequent or difficult evacuation of feces. [NIH] Constriction: The act of constricting. [NIH] 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] Controlled study: An experiment or clinical trial that includes a comparison (control) group. [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]

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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] Corpuscle: A small mass or body; a sensory nerve end bulb; a cell, especially that of the blood or the lymph. [NIH] Cortex: The outer layer of an organ or other body structure, as distinguished from the internal substance. [EU] Cortical: Pertaining to or of the nature of a cortex or bark. [EU] Corticosteroid: Any of the steroids elaborated by the adrenal cortex (excluding the sex hormones of adrenal origin) in response to the release of corticotrophin (adrenocorticotropic hormone) by the pituitary gland, to any of the synthetic equivalents of these steroids, or to angiotensin II. They are divided, according to their predominant biological activity, into three major groups: glucocorticoids, chiefly influencing carbohydrate, fat, and protein metabolism; mineralocorticoids, affecting the regulation of electrolyte and water balance; and C19 androgens. Some corticosteroids exhibit both types of activity in varying degrees, and others exert only one type of effect. The corticosteroids are used clinically for hormonal replacement therapy, for suppression of ACTH secretion by the anterior pituitary, as antineoplastic, antiallergic, and anti-inflammatory agents, and to suppress the immune response. Called also adrenocortical hormone and corticoid. [EU] 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) end of the body. [EU] 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] Creatinine clearance: A test that measures how efficiently the kidneys remove creatinine and other wastes from the blood. Low creatinine clearance indicates impaired kidney function. [NIH] Cribriform: Pierced with small holes as in a sieve. Refers to the appearance of a tumor when viewed under a microscope. The tumor appears to have open spaces or small holes inside. [NIH]

Crossing-over: The exchange of corresponding segments between chromatids of homologous chromosomes during meiosia, forming a chiasma. [NIH] Cryoglobulinemia: A condition characterized by the presence of abnormal or abnormal quantities of cryoglobulins in the blood. They are precipitated into the microvasculature on exposure to cold and cause restricted blood flow in exposed areas. [NIH] Cultured cells: Animal or human cells that are grown in the laboratory. [NIH] 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]

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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] Cyclin: Molecule that regulates the cell cycle. [NIH] Cyclophosphamide: Precursor of an alkylating nitrogen mustard antineoplastic and immunosuppressive agent that must be activated in the liver to form the active aldophosphamide. It is used in the treatment of lymphomas, leukemias, etc. Its side effect, alopecia, has been made use of in defleecing sheep. Cyclophosphamide may also cause sterility, birth defects, mutations, and cancer. [NIH] Cyclosporine: A drug used to help reduce the risk of rejection of organ and bone marrow transplants by the body. It is also used in clinical trials to make cancer cells more sensitive to anticancer drugs. [NIH] Cysteine: A thiol-containing non-essential amino acid that is oxidized to form cystine. [NIH] Cysteinyl: Enzyme released by the cell at a crucial stage in apoptosis in order to shred all cellular proteins. [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]

Cytochrome: Any electron transfer hemoprotein having a mode of action in which the transfer of a single electron is effected by a reversible valence change of the central iron atom of the heme prosthetic group between the +2 and +3 oxidation states; classified as cytochromes a in which the heme contains a formyl side chain, cytochromes b, which contain protoheme or a closely similar heme that is not covalently bound to the protein, cytochromes c in which protoheme or other heme is covalently bound to the protein, and cytochromes d in which the iron-tetrapyrrole has fewer conjugated double bonds than the hemes have. Well-known cytochromes have been numbered consecutively within groups and are designated by subscripts (beginning with no subscript), e.g. cytochromes c, c1, C2, . New cytochromes are named according to the wavelength in nanometres of the absorption maximum of the a-band of the iron (II) form in pyridine, e.g., c-555. [EU] Cytochrome b: Cytochromes (electron-transporting proteins) with protoheme or a related heme as the prosthetic group. The prosthetic group is not covalently bound to the protein moiety. [NIH] Cytokine: Small but highly potent protein that modulates the activity of many cell types, including T and B cells. [NIH] Cytokinesis: Division of the rest of cell. [NIH] Cytoplasm: The protoplasm of a cell exclusive of that of the nucleus; it consists of a continuous aqueous solution (cytosol) and the organelles and inclusions suspended in it (phaneroplasm), and is the site of most of the chemical activities of the cell. [EU] Cytoskeleton: The network of filaments, tubules, and interconnecting filamentous bridges which give shape, structure, and organization to the cytoplasm. [NIH] Cytotoxic: Cell-killing. [NIH] Cytotoxicity: Quality of being capable of producing a specific toxic action upon cells of special organs. [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]

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Decarboxylation: The removal of a carboxyl group, usually in the form of carbon dioxide, from a chemical compound. [NIH] Degenerative: Undergoing degeneration : tending to degenerate; having the character of or involving degeneration; causing or tending to cause degeneration. [EU] Dehydration: The condition that results from excessive loss of body water. [NIH] Deletion: A genetic rearrangement through loss of segments of DNA (chromosomes), bringing sequences, which are normally separated, into close proximity. [NIH] Demecolcine: An alkaloid isolated from Colchicum autumnale L. and used as an antineoplastic. [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] Demography: Statistical interpretation and description of a population with reference to distribution, composition, or structure. [NIH] Demyelinating Diseases: Diseases characterized by loss or dysfunction of myelin in the central or peripheral nervous system. [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] 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 cells, whose axons pass through the polymorphic layer ending on the dendrites of pyramidal cells in the hippocampus. [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] Dermatosis: Any skin disease, especially one not characterized by inflammation. [EU] Desensitization: The prevention or reduction of immediate hypersensitivity reactions by administration of graded doses of allergen; called also hyposensitization and immunotherapy. [EU] Deuterium: Deuterium. The stable isotope of hydrogen. It has one neutron and one proton in the nucleus. [NIH] Deuterium Oxide: The isotopic compound of hydrogen of mass 2 (deuterium) with oxygen. (From Grant & Hackh's Chemical Dictionary, 5th ed) It is used to study mechanisms and rates of chemical or nuclear reactions, as well as biological processes. [NIH] Diagnostic procedure: A method used to identify a disease. [NIH] Diarrhea: Passage of excessively liquid or excessively frequent stools. [NIH] Diastolic: Of or pertaining to the diastole. [EU] 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]

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Digestion: The process of breakdown of food for metabolism and use by the body. [NIH] Dimerization: The process by which two molecules of the same chemical composition form a condensation product or polymer. [NIH] Diploid: Having two sets of chromosomes. [NIH] Direct: 1. Straight; in a straight line. 2. Performed immediately and without the intervention of subsidiary means. [EU] 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] Disposition: A tendency either physical or mental toward certain diseases. [EU] Dissociation: 1. The act of separating or state of being separated. 2. The separation of a molecule into two or more fragments (atoms, molecules, ions, or free radicals) produced by the absorption of light or thermal energy or by solvation. 3. In psychology, a defense mechanism in which a group of mental processes are segregated from the rest of a person's mental activity in order to avoid emotional distress, as in the dissociative disorders (q.v.), or in which an idea or object is segregated from its emotional significance; in the first sense it is roughly equivalent to splitting, in the second, to isolation. 4. A defect of mental integration in which one or more groups of mental processes become separated off from normal consciousness and, thus separated, function as a unitary whole. [EU] 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] Diuretic: A drug that increases the production of urine. [NIH] Dolastatin 10: An anticancer drug that belongs to the family of drugs called mitotic inhibitors. [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] Dorsal: 1. Pertaining to the back or to any dorsum. 2. Denoting a position more toward the back surface than some other object of reference; same as posterior in human anatomy; superior in the anatomy of quadrupeds. [EU] Dorsum: A plate of bone which forms the posterior boundary of the sella turcica. [NIH] Dose-dependent: Refers to the effects of treatment with a drug. If the effects change when the dose of the drug is changed, the effects are said to be dose dependent. [NIH] Double-blind: Pertaining to a clinical trial or other experiment in which neither the subject nor the person administering treatment knows which treatment any particular subject is receiving. [EU] Doxorubicin: Antineoplastic antibiotic obtained from Streptomyces peucetics. It is a hydroxy derivative of daunorubicin and is used in treatment of both leukemia and solid tumors. [NIH] Drug Design: The molecular designing of drugs for specific purposes (such as DNA-

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binding, enzyme inhibition, anti-cancer efficacy, etc.) based on knowledge of molecular properties such as activity of functional groups, molecular geometry, and electronic structure, and also on information cataloged on analogous molecules. Drug design is generally computer-assisted molecular modeling and does not include pharmacokinetics, dosage analysis, or drug administration analysis. [NIH] Drug Interactions: The action of a drug that may affect the activity, metabolism, or toxicity of another drug. [NIH] Drug Resistance: Diminished or failed response of an organism, disease or tissue to the intended effectiveness of a chemical or drug. It should be differentiated from drug tolerance which is the progressive diminution of the susceptibility of a human or animal to the effects of a drug, as a result of continued administration. [NIH] Drug Tolerance: Progressive diminution of the susceptibility of a human or animal to the effects of a drug, resulting from its continued administration. It should be differentiated from drug resistance wherein an organism, disease, or tissue fails to respond to the intended effectiveness of a chemical or drug. It should also be differentiated from maximum tolerated dose and no-observed-adverse-effect level. [NIH] Duct: A tube through which body fluids pass. [NIH] Duodenum: The first part of the small intestine. [NIH] Dura mater: The outermost, toughest, and most fibrous of the three membranes (meninges) covering the brain and spinal cord; called also pachymeninx. [EU] Dyes: Chemical substances that are used to stain and color other materials. The coloring may or may not be permanent. Dyes can also be used as therapeutic agents and test reagents in medicine and scientific research. [NIH] Dysplasia: Cells that look abnormal under a microscope but are not cancer. [NIH] Dyspnea: Difficult or labored breathing. [NIH] Echinacea: A genus of perennial herbs used topically and internally. It contains echinacoside, glycosides, inulin, isobutyl amides, resin, and sesquiterpenes. [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] Efferent: Nerve fibers which conduct impulses from the central nervous system to muscles and glands. [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] Elastin: The protein that gives flexibility to tissues. [NIH] Electrolysis: Destruction by passage of a galvanic electric current, as in disintegration of a chemical compound in solution. [NIH] Electrolyte: A substance that dissociates into ions when fused or in solution, and thus becomes capable of conducting electricity; an ionic solute. [EU] Electrons: Stable elementary particles having the smallest known negative charge, present in all elements; also called negatrons. Positively charged electrons are called positrons. The numbers, energies and arrangement of electrons around atomic nuclei determine the

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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]

Embolism: Blocking of a blood vessel by a blood clot or foreign matter that has been transported from a distant site by the blood stream. [NIH] Embryo: The prenatal stage of mammalian development characterized by rapid morphological changes and the differentiation of basic structures. [NIH] Embryogenesis: The process of embryo or embryoid formation, whether by sexual (zygotic) or asexual means. In asexual embryogenesis embryoids arise directly from the explant or on intermediary callus tissue. In some cases they arise from individual cells (somatic cell embryoge). [NIH] 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] Endarterectomy: Surgical excision, performed under general anesthesia, of the atheromatous tunica intima of an artery. When reconstruction of an artery is performed as an endovascular procedure through a catheter, it is called atherectomy. [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] Endogenous: Produced inside an organism or cell. The opposite is external (exogenous) production. [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] End-stage renal: Total chronic kidney failure. When the kidneys fail, the body retains fluid and harmful wastes build up. A person with ESRD needs treatment to replace the work of the failed kidneys. [NIH] 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]

Enzymatic: Phase where enzyme cuts the precursor protein. [NIH] Enzyme: A protein that speeds up chemical reactions in the body. [NIH] Eosinophilia: Abnormal increase in eosinophils in the blood, tissues or organs. [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

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uniform in size and stainable by eosin. [NIH] Epidemiological: Relating to, or involving epidemiology. [EU] Epidermal: Pertaining to or resembling epidermis. Called also epidermic or epidermoid. [EU] Epidermis: Nonvascular layer of the skin. It is made up, from within outward, of five layers: 1) basal layer (stratum basale epidermidis); 2) spinous layer (stratum spinosum epidermidis); 3) granular layer (stratum granulosum epidermidis); 4) clear layer (stratum lucidum epidermidis); and 5) horny layer (stratum corneum epidermidis). [NIH] Epinephrine: The active sympathomimetic hormone from the adrenal medulla in most species. It stimulates both the alpha- and beta- adrenergic systems, causes systemic vasoconstriction and gastrointestinal relaxation, stimulates the heart, and dilates bronchi and cerebral vessels. It is used in asthma and cardiac failure and to delay absorption of local anesthetics. [NIH] Epithelial: Refers to the cells that line the internal and external surfaces of the body. [NIH] Epithelial Cells: Cells that line the inner and outer surfaces of the body. [NIH] Epithelium: One or more layers of epithelial cells, supported by the basal lamina, which covers the inner or outer surfaces of the body. [NIH] Erythema: Redness of the skin produced by congestion of the capillaries. This condition may result from a variety of causes. [NIH] Erythema Nodosum: An erythematous eruption commonly associated with drug reactions or infection and characterized by inflammatory nodules that are usually tender, multiple, and bilateral. These nodules are located predominantly on the shins with less common occurrence on the thighs and forearms. They undergo characteristic color changes ending in temporary bruise-like areas. This condition usually subsides in 3-6 weeks without scarring or atrophy. [NIH] Erythrocyte Membrane: The semipermeable outer portion of the red corpuscle. It is known as a 'ghost' after hemolysis. [NIH] Erythrocytes: Red blood cells. Mature erythrocytes are non-nucleated, biconcave disks containing hemoglobin whose function is to transport oxygen. [NIH] Erythromycin: A bacteriostatic antibiotic substance produced by Streptomyces erythreus. Erythromycin A is considered its major active component. In sensitive organisms, it inhibits protein synthesis by binding to 50S ribosomal subunits. This binding process inhibits peptidyl transferase activity and interferes with translocation of amino acids during translation and assembly of proteins. [NIH] Esophagus: The muscular tube through which food passes from the throat to the stomach. [NIH]

Estradiol: The most potent mammalian estrogenic hormone. It is produced in the ovary, placenta, testis, and possibly the adrenal cortex. [NIH] Estrogen: One of the two female sex hormones. [NIH] Ethanol: A clear, colorless liquid rapidly absorbed from the gastrointestinal tract and distributed throughout the body. It has bactericidal activity and is used often as a topical disinfectant. It is widely used as a solvent and preservative in pharmaceutical preparations as well as serving as the primary ingredient in alcoholic beverages. [NIH] Ether: One of a class of organic compounds in which any two organic radicals are attached directly to a single oxygen atom. [NIH] Ethidium: A trypanocidal agent and possible antiviral agent that is widely used in experimental cell biology and biochemistry. Ethidium has several experimentally useful

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properties including binding to nucleic acids, noncompetitive inhibition of nicotinic acetylcholine receptors, and fluorescence among others. It is most commonly used as the bromide. [NIH] Ethmoid: An unpaired cranial bone which helps form the medial walls of the orbits and contains the themoidal air cells which drain into the nose. [NIH] Etoposide: A semisynthetic derivative of podophyllotoxin that exhibits antitumor activity. Etoposide inhibits DNA synthesis by forming a complex with topoisomerase II and DNA. This complex induces breaks in double stranded DNA and prevents repair by topoisomerase II binding. Accumulated breaks in DNA prevent entry into the mitotic phase of cell division, and lead to cell death. Etoposide acts primarily in the G2 and S phases of the cell cycle. [NIH] Eukaryotic Cells: Cells of the higher organisms, containing a true nucleus bounded by a nuclear membrane. [NIH] Evacuation: An emptying, as of the bowels. [EU] Exfoliation: A falling off in scales or layers. [EU] Exocrine: Secreting outwardly, via a duct. [EU] 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] Exon: The part of the DNA that encodes the information for the actual amino acid sequence of the protein. In many eucaryotic genes, the coding sequences consist of a series of exons alternating with intron sequences. [NIH] Expiration: The act of breathing out, or expelling air from the lungs. [EU] External-beam radiation: Radiation therapy that uses a machine to aim high-energy rays at the cancer. Also called external 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] Extraction: The process or act of pulling or drawing out. [EU] Extremity: A limb; an arm or leg (membrum); sometimes applied specifically to a hand or foot. [EU] Facial: Of or pertaining to the face. [EU] Facial Nerve: The 7th cranial nerve. The facial nerve has two parts, the larger motor root which may be called the facial nerve proper, and the smaller intermediate or sensory root. Together they provide efferent innervation to the muscles of facial expression and to the lacrimal and salivary glands, and convey afferent information for taste from the anterior two-thirds of the tongue and for touch from the external ear. [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] 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]

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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] Fibrinogen: Plasma glycoprotein clotted by thrombin, composed of a dimer of three nonidentical pairs of polypeptide chains (alpha, beta, gamma) held together by disulfide bonds. Fibrinogen clotting is a sol-gel change involving complex molecular arrangements: whereas fibrinogen is cleaved by thrombin to form polypeptides A and B, the proteolytic action of other enzymes yields different fibrinogen degradation products. [NIH] Fibroblasts: Connective tissue cells which secrete an extracellular matrix rich in collagen and other macromolecules. [NIH] Fibronectin: An adhesive glycoprotein. One form circulates in plasma, acting as an opsonin; another is a cell-surface protein which mediates cellular adhesive interactions. [NIH] Fibrosis: Any pathological condition where fibrous connective tissue invades any organ, usually as a consequence of inflammation or other injury. [NIH] 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] Flatulence: Production or presence of gas in the gastrointestinal tract which may be expelled through the anus. [NIH] Flavopiridol: Belongs to the family of anticancer drugs called flavinols. [NIH] Fluid Therapy: Therapy whose basic objective is to restore the volume and composition of the body fluids to normal with respect to water-electrolyte balance. Fluids may be administered intravenously, orally, by intermittent gavage, or by hypodermoclysis. [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] Fluorescence Polarization: Measurement of the polarization of fluorescent light from solutions or microscopic specimens. It is used to provide information concerning molecular size, shape, and conformation, molecular anisotropy, electronic energy transfer, molecular interaction, including dye and coenzyme binding, and the antigen-antibody reaction. [NIH]

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Fluorouracil: A pyrimidine analog that acts as an antineoplastic antimetabolite and also has immunosuppressant. It interferes with DNA synthesis by blocking the thymidylate synthetase conversion of deoxyuridylic acid to thymidylic acid. [NIH] Forearm: The part between the elbow and the wrist. [NIH] Fovea: The central part of the macula that provides the sharpest vision. [NIH] Fractionation: Dividing the total dose of radiation therapy into several smaller, equal doses delivered over a period of several days. [NIH] Free Radicals: Highly reactive molecules with an unsatisfied electron valence pair. Free radicals are produced in both normal and pathological processes. They are proven or suspected agents of tissue damage in a wide variety of circumstances including radiation, damage from environment chemicals, and aging. Natural and pharmacological prevention of free radical damage is being actively investigated. [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] Fungicide: An agent that destroys fungi. [EU] Fusaric Acid: A picolinic acid derivative isolated from various Fusarium species. It has been proposed for a variety of therapeutic applications but is primarily used as a research tool. Its mechanisms of action are poorly understood. It probably inhibits dopamine betahydroxylase, the enzyme that converts dopamine to norepinephrine. It may also have other actions, including the inhibition of cell proliferation and DNA synthesis. [NIH] Galactosides: Glycosides formed by the reaction of the hydroxyl group on the anomeric carbon atom of galactose with an alcohol to form an acetal. They include both alpha- and beta-galactosides. [NIH] Gallbladder: The pear-shaped organ that sits below the liver. Bile is concentrated and stored in the gallbladder. [NIH] Gallium: A rare, metallic element designated by the symbol, Ga, atomic number 31, and atomic weight 69.72. [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] 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] Gastric: Having to do with the stomach. [NIH] 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]

Gastrointestinal: Refers to the stomach and intestines. [NIH] Gastrointestinal tract: The stomach and intestines. [NIH]

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Gemfibrozil: A lipid-regulating agent that lowers elevated serum lipids primarily by decreasing serum triglycerides with a variable reduction in total cholesterol. These decreases occur primarily in the VLDL fraction and less frequently in the LDL fraction. Gemfibrozil increases HDL subfractions HDL2 and HDL3 as well as apolipoproteins A-I and A-II. Its mechanism of action has not been definitely established. [NIH] Gene: The functional and physical unit of heredity passed from parent to offspring. Genes are pieces of DNA, and most genes contain the information for making a specific protein. [NIH]

Gene Expression: The phenotypic manifestation of a gene or genes by the processes of gene action. [NIH] 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] Genital: Pertaining to the genitalia. [EU] Genitourinary: Pertaining to the genital and urinary organs; urogenital; urinosexual. [EU] Genotype: The genetic constitution of the individual; the characterization of the genes. [NIH] Germ Cells: The reproductive cells in multicellular organisms. [NIH] Gland: An organ that produces and releases one or more substances for use in the body. Some glands produce fluids that affect tissues or organs. Others produce hormones or participate in blood production. [NIH] Glomerular: Pertaining to or of the nature of a glomerulus, especially a renal glomerulus. [EU]

Glomeruli: Plural of glomerulus. [NIH] Glomerulus: A tiny set of looping blood vessels in the nephron where blood is filtered in the kidney. [NIH] Glottis: The vocal apparatus of the larynx, consisting of the true vocal cords (plica vocalis) and the opening between them (rima glottidis). [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 therapeutically in fluid and nutrient replacement. [NIH] Glutathione Peroxidase: An enzyme catalyzing the oxidation of 2 moles of glutathione in the presence of hydrogen peroxide to yield oxidized glutathione and water. EC 1.11.1.9. [NIH]

Glycerol: A trihydroxy sugar alcohol that is an intermediate in carbohydrate and lipid metabolism. It is used as a solvent, emollient, pharmaceutical agent, and sweetening agent. [NIH]

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Glycerophospholipids: Derivatives of phosphatidic acid in which the hydrophobic regions are composed of two fatty acids and a polar alcohol is joined to the C-3 position of glycerol through a phosphodiester bond. They are named according to their polar head groups, such as phosphatidylcholine and phosphatidylethanolamine. [NIH] Glycine: A non-essential amino acid. It is found primarily in gelatin and silk fibroin and used therapeutically as a nutrient. It is also a fast inhibitory neurotransmitter. [NIH] 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] Gonadal: Pertaining to a gonad. [EU] Gout: Hereditary metabolic disorder characterized by recurrent acute arthritis, hyperuricemia and deposition of sodium urate in and around the joints, sometimes with formation of uric acid calculi. [NIH] Governing Board: The group in which legal authority is vested for the control of healthrelated institutions and organizations. [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] 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] Granulation Tissue: A vascular connective tissue formed on the surface of a healing wound, ulcer, or inflamed tissue. It consists of new capillaries and an infiltrate containing lymphoid cells, macrophages, and plasma cells. [NIH] Granule: A small pill made from sucrose. [EU] Granulocyte: A type of white blood cell that fights bacterial infection. Neutrophils, eosinophils, and basophils are granulocytes. [NIH] Granulocyte Colony-Stimulating Factor: A glycoprotein of MW 25 kDa containing internal disulfide bonds. It induces the survival, proliferation, and differentiation of neutrophilic granulocyte precursor cells and functionally activates mature blood neutrophils. Among the family of colony-stimulating factors, G-CSF is the most potent inducer of terminal differentiation to granulocytes and macrophages of leukemic myeloid cell lines. [NIH] Granulomatous Disease, Chronic: A recessive X-linked defect of leukocyte function in which phagocytic cells ingest but fail to digest bacteria, resulting in recurring bacterial infections with granuloma formation. [NIH] Griseofulvin: An antifungal antibiotic. Griseofulvin may be given by mouth in the treatment of tinea infections. [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] Guanine: One of the four DNA bases. [NIH] Guanosine Triphosphate: Guanosine 5'-(tetrahydrogen triphosphate). A guanine nucleotide

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containing three phosphate groups esterified to the sugar moiety. [NIH] Haemodialysis: The removal of certain elements from the blood by virtue of the difference in the rates of their diffusion through a semipermeable membrane, e.g., by means of a haemodialyzer. [EU] 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] Haploid: An organism with one basic chromosome set, symbolized by n; the normal condition of gametes in diploids. [NIH] Haptens: Small antigenic determinants capable of eliciting an immune response only when coupled to a carrier. Haptens bind to antibodies but by themselves cannot elicit an antibody response. [NIH] Hay Fever: A seasonal variety of allergic rhinitis, marked by acute conjunctivitis with lacrimation and itching, regarded as an allergic condition triggered by specific allergens. [NIH]

Heart failure: Loss of pumping ability by the heart, often accompanied by fatigue, breathlessness, and excess fluid accumulation in body tissues. [NIH] Hemolysis: The destruction of erythrocytes by many different causal agents such as antibodies, bacteria, chemicals, temperature, and changes in tonicity. [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]

Hepatic: Refers to the liver. [NIH] Hepatic Encephalopathy: A condition that may cause loss of consciousness and coma. It is usually the result of advanced liver disease. Also called hepatic coma. [NIH] Hepatitis: Inflammation of the liver and liver disease involving degenerative or necrotic alterations of hepatocytes. [NIH] Hepatitis C: A form of hepatitis, similar to type B post-transfusion hepatitis, but caused by a virus which is serologically distinct from the agents of hepatitis A, B, and E, and which may persist in the blood of chronic asymptomatic carriers. Hepatitis C is parenterally transmitted and associated with transfusions and drug abuse. [NIH] Hepatocellular: Pertaining to or affecting liver cells. [EU] Hepatocellular carcinoma: A type of adenocarcinoma, the most common type of liver tumor. [NIH] Hepatocyte: A liver cell. [NIH] Herbicide: A chemical that kills plants. [NIH] Hereditary: Of, relating to, or denoting factors that can be transmitted genetically from one generation to another. [NIH] Heredity: 1. The genetic transmission of a particular quality or trait from parent to offspring. 2. The genetic constitution of an individual. [EU] Heterochromatin: The portion of chromosome material that remains condensed and is transcriptionally inactive during interphase. [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.

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[NIH]

Heterozygotes: Having unlike alleles at one or more corresponding loci on homologous chromosomes. [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] Histamine Release: The secretion of histamine from mast cell and basophil granules by exocytosis. This can be initiated by a number of factors, all of which involve binding of IgE, cross-linked by antigen, to the mast cell or basophil's Fc receptors. Once released, histamine binds to a number of different target cell receptors and exerts a wide variety of effects. [NIH] Histidine: An essential amino acid important in a number of metabolic processes. It is required for the production of histamine. [NIH] Histones: Small chromosomal proteins (approx 12-20 kD) possessing an open, unfolded structure and attached to the DNA in cell nuclei by ionic linkages. Classification into the various types (designated histone I, histone II, etc.) is based on the relative amounts of arginine and lysine in each. [NIH] Homoharringtonine: An anticancer drug that belongs to the plant alkaloid family of drugs. [NIH]

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] 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] Hybridomas: Cells artificially created by fusion of activated lymphocytes with neoplastic cells. The resulting hybrid cells are cloned and produce pure or "monoclonal" antibodies or T-cell products, identical to those produced by the immunologically competent parent, and continually grow and divide as the neoplastic parent. [NIH] Hydration: Combining with water. [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] Hydroxides: Inorganic compounds that contain the OH- group. [NIH] Hydroxyl Radical: The univalent radical OH that is present in hydroxides, alcohols, phenols, glycols. [NIH]

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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] Hyperbilirubinemia: Pathologic process consisting of an abnormal increase in the amount of bilirubin in the circulating blood, which may result in jaundice. [NIH] Hypersensitivity: Altered reactivity to an antigen, which can result in pathologic reactions upon subsequent exposure to that particular antigen. [NIH] Hypertension: Persistently high arterial blood pressure. Currently accepted threshold levels are 140 mm Hg systolic and 90 mm Hg diastolic pressure. [NIH] Hyperuricemia: A buildup of uric acid (a byproduct of metabolism) in the blood; a side effect of some anticancer drugs. [NIH] Hypnotic: A drug that acts to induce sleep. [EU] Hypokinesia: Slow or diminished movement of body musculature. It may be associated with basal ganglia diseases; mental disorders; prolonged inactivity due to illness; experimental protocols used to evaluate the physiologic effects of immobility; and other conditions. [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] Idiopathic: Describes a disease of unknown cause. [NIH] Imidazole: C3H4N2. The ring is present in polybenzimidazoles. [NIH] Immune response: The activity of the immune system against foreign substances (antigens). [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] Immunocompromised: Having a weakened immune system caused by certain diseases or treatments. [NIH] Immunodeficiency: The decreased ability of the body to fight infection and disease. [NIH] Immunologic: The ability of the antibody-forming system to recall a previous experience with an antigen and to respond to a second exposure with the prompt production of large amounts of antibody. [NIH] Immunology: The study of the body's immune system. [NIH] Immunosuppressant: An agent capable of suppressing immune responses. [EU] Immunosuppression: Deliberate prevention or diminution of the host's immune response. It may be nonspecific as in the administration of immunosuppressive agents (drugs or

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radiation) or by lymphocyte depletion or may be specific as in desensitization or the simultaneous administration of antigen and immunosuppressive drugs. [NIH] Immunosuppressive: Describes the ability to lower immune system responses. [NIH] Immunosuppressive Agents: Agents that suppress immune function by one of several mechanisms of action. Classical cytotoxic immunosuppressants act by inhibiting DNA synthesis. Others may act through activation of suppressor T-cell populations or by inhibiting the activation of helper cells. While immunosuppression has been brought about in the past primarily to prevent rejection of transplanted organs, new applications involving mediation of the effects of interleukins and other cytokines are emerging. [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] Implant radiation: A procedure in which radioactive material sealed in needles, seeds, wires, or catheters is placed directly into or near the tumor. Also called [NIH] In situ: In the natural or normal place; confined to the site of origin without invasion of neighbouring tissues. [EU] In Situ Hybridization: A technique that localizes specific nucleic acid sequences within intact chromosomes, eukaryotic cells, or bacterial cells through the use of specific nucleic acid-labeled probes. [NIH] In vitro: In the laboratory (outside the body). The opposite of in vivo (in the body). [NIH] In vivo: In the body. The opposite of in vitro (outside the body or in the laboratory). [NIH] Incision: A cut made in the body during surgery. [NIH] Incontinence: Inability to control the flow of urine from the bladder (urinary incontinence) or the escape of stool from the rectum (fecal incontinence). [NIH] 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] 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] 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]

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]

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Inflammation: A pathological process characterized by injury or destruction of tissues caused by a variety of cytologic and chemical reactions. It is usually manifested by typical signs of pain, heat, redness, swelling, and loss of function. [NIH] Inflammatory bowel disease: A general term that refers to the inflammation of the colon and rectum. Inflammatory bowel disease includes ulcerative colitis and Crohn's disease. [NIH]

Ingestion: Taking into the body by mouth [NIH] 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] 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] 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] 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 bacterial products. It is the major interferon produced by virus-induced leukocyte cultures and, in addition to its pronounced antiviral activity, it causes activation of NK cells. [NIH] Interleukin-1: A soluble factor produced by monocytes, macrophages, and other cells which activates T-lymphocytes and potentiates their response to mitogens or antigens. IL-1 consists of two distinct forms, IL-1 alpha and IL-1 beta which perform the same functions but are distinct proteins. The biological effects of IL-1 include the ability to replace macrophage requirements for T-cell activation. The factor is distinct from interleukin-2. [NIH] Interleukin-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] Interleukin-6: Factor that stimulates the growth and differentiation of human B-cells and is also a growth factor for hybridomas and plasmacytomas. It is produced by many different cells including T-cells, monocytes, and fibroblasts. [NIH] Intermittent: Occurring at separated intervals; having periods of cessation of activity. [EU] Internal radiation: A procedure in which radioactive material sealed in needles, seeds, wires, or catheters is placed directly into or near the tumor. Also called brachytherapy, implant radiation, or interstitial radiation therapy. [NIH] Interphase: The interval between two successive cell divisions during which the chromosomes are not individually distinguishable and DNA replication occurs. [NIH] Interstitial: Pertaining to or situated between parts or in the interspaces of a tissue. [EU] Interstitial Collagenase: A member of the metalloproteinase family of enzymes that is principally responsible for cleaving fibrillar collagen. It can degrade interstitial collagens,

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types I, II and III. EC 3.4.24.7. [NIH] Intestinal: Having to do with the intestines. [NIH] Intestinal Mucosa: The surface lining of the intestines where the cells absorb nutrients. [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] Intracranial Hypertension: Increased pressure within the cranial vault. This may result from several conditions, including hydrocephalus; brain edema; intracranial masses; severe systemic hypertension; pseudotumor cerebri; and other disorders. [NIH] Intrahepatic: Within the liver. [NIH] Intramuscular: IM. Within or into muscle. [NIH] Intraocular: Within the eye. [EU] Intraocular pressure: Pressure of the fluid inside the eye; normal IOP varies among individuals. [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] 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]

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] Irradiation: The use of high-energy radiation from x-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 from materials called radioisotopes. Radioisotopes produce radiation and can be placed in or near the tumor or in the area near cancer cells. This type of radiation treatment is called internal radiation therapy, implant radiation, interstitial radiation, or brachytherapy. Systemic radiation therapy uses a radioactive substance, such as a radiolabeled monoclonal antibody, that circulates throughout the body. Irradiation is also called radiation therapy, radiotherapy, and x-ray therapy. [NIH] Irritable Bowel Syndrome: A disorder that comes and goes. Nerves that control the muscles in the GI tract are too active. The GI tract becomes sensitive to food, stool, gas, and stress. Causes abdominal pain, bloating, and constipation or diarrhea. Also called spastic colon or mucous colitis. [NIH] Ischemia: Deficiency of blood in a part, due to functional constriction or actual obstruction of a blood vessel. [EU] Jaundice: A clinical manifestation of hyperbilirubinemia, consisting of deposition of bile

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pigments in the skin, resulting in a yellowish staining of the skin and mucous membranes. [NIH]

Kb: A measure of the length of DNA fragments, 1 Kb = 1000 base pairs. The largest DNA fragments are up to 50 kilobases long. [NIH] Keratin: A class of fibrous proteins or scleroproteins important both as structural proteins and as keys to the study of protein conformation. The family represents the principal constituent of epidermis, hair, nails, horny tissues, and the organic matrix of tooth enamel. Two major conformational groups have been characterized, alpha-keratin, whose peptide backbone forms an alpha-helix, and beta-keratin, whose backbone forms a zigzag or pleated sheet structure. [NIH] Keratinocytes: Epidermal cells which synthesize keratin and undergo characteristic changes as they move upward from the basal layers of the epidermis to the cornified (horny) layer of the skin. Successive stages of differentiation of the keratinocytes forming the epidermal layers are basal cell, spinous or prickle cell, and the granular cell. [NIH] Kidney Cortex: The outer zone of the kidney, beneath the capsule, consisting of kidney glomerulus; kidney tubules, distal; and kidney tubules, proximal. [NIH] Kidney stone: A stone that develops from crystals that form in urine and build up on the inner surfaces of the kidney, in the renal pelvis, or in the ureters. [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]

Kinesin: A microtubule-associated mechanical adenosine triphosphatase, that uses the energy of ATP hydrolysis to move organelles along microtubules toward the plus end of the microtubule. The protein is found in squid axoplasm, optic lobes, and in bovine brain. Bovine kinesin is a heterotetramer composed of two heavy (120 kDa) and two light (62 kDa) chains. EC 3.6.1.-. [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] Leg Ulcer: Ulceration of the skin and underlying structures of the lower extremity. About 90% of the cases are due to venous insufficiency (varicose ulcer), 5% to arterial disease, and the remaining 5% to other causes. [NIH] Lentivirus: A genus of the family Retroviridae consisting of non-oncogenic retroviruses that produce multi-organ diseases characterized by long incubation periods and persistent infection. Lentiviruses are unique in that they contain open reading frames (ORFs) between the pol and env genes and in the 3' env region. Five serogroups are recognized, reflecting the mammalian hosts with which they are associated. HIV-1 is the type species. [NIH] Lesion: An area of abnormal tissue change. [NIH] Lethal: Deadly, fatal. [EU] Lethargy: Abnormal drowsiness or stupor; a condition of indifference. [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]

Leukaemia: An acute or chronic disease of unknown cause in man and other warm-blooded animals that involves the blood-forming organs, is characterized by an abnormal increase in the number of leucocytes in the tissues of the body with or without a corresponding increase of those in the circulating blood, and is classified according of the type leucocyte most

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prominently involved. [EU] Leukemia: Cancer of blood-forming tissue. [NIH] Levamisole: An antiparasitic drug that is also being studied in cancer therapy with fluorouracil. [NIH] Ligaments: Shiny, flexible bands of fibrous tissue connecting together articular extremities of bones. They are pliant, tough, and inextensile. [NIH] Ligands: A RNA simulation method developed by the MIT. [NIH] Light microscope: A microscope (device to magnify small objects) in which objects are lit directly by white light. [NIH] Lipid: Fat. [NIH] 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] Liver: A large, glandular organ located in the upper abdomen. The liver cleanses the blood and aids in digestion by secreting bile. [NIH] Liver Cirrhosis: Liver disease in which the normal microcirculation, the gross vascular anatomy, and the hepatic architecture have been variably destroyed and altered with fibrous septa surrounding regenerated or regenerating parenchymal nodules. [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] Locomotion: Movement or the ability to move from one place or another. It can refer to humans, vertebrate or invertebrate animals, and microorganisms. [NIH] Lovastatin: A fungal metabolite isolated from cultures of Aspergillus terreus. The compound is a potent anticholesteremic agent. It inhibits 3-hydroxy-3-methylglutaryl coenzyme A reductase (hydroxymethylglutaryl CoA reductases), which is the rate-limiting enzyme in cholesterol biosynthesis. It also stimulates the production of low-density lipoprotein receptors in the liver. [NIH] Lumbar: Pertaining to the loins, the part of the back between the thorax and the pelvis. [EU] Lymph: The almost colorless fluid that travels through the lymphatic system and carries cells that help fight infection and disease. [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] Lymphocyte Depletion: Immunosuppression by reduction of circulating lymphocytes or by T-cell depletion of bone marrow. The former may be accomplished in vivo by thoracic duct drainage or administration of antilymphocyte serum. The latter is performed ex vivo on bone marrow before its transplantation. [NIH] Lymphocytes: White blood cells formed in the body's lymphoid tissue. The nucleus is round or ovoid with coarse, irregularly clumped chromatin while the cytoplasm is typically pale blue with azurophilic (if any) granules. Most lymphocytes can be classified as either T or B (with subpopulations of each); those with characteristics of neither major class are called null cells. [NIH]

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Lymphocytic: Referring to lymphocytes, a type of white blood cell. [NIH] Lymphoid: Referring to lymphocytes, a type of white blood cell. Also refers to tissue in which lymphocytes develop. [NIH] Lymphoma: A general term for various neoplastic diseases of the lymphoid tissue. [NIH] 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] Malignant: Cancerous; a growth with a tendency to invade and destroy nearby tissue and spread to other parts of the body. [NIH] Malnutrition: A condition caused by not eating enough food or not eating a balanced diet. [NIH]

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] MEDLINE: An online database of MEDLARS, the computerized bibliographic Medical Literature Analysis and Retrieval System of the National Library of Medicine. [NIH] Meiosis: A special method of cell division, occurring in maturation of the germ cells, by means of which each daughter nucleus receives half the number of chromosomes characteristic of the somatic cells of the species. [NIH] Melanin: The substance that gives the skin its color. [NIH] Melanocytes: Epidermal dendritic pigment cells which control long-term morphological color changes by alteration in their number or in the amount of pigment they produce and store in the pigment containing organelles called melanosomes. Melanophores are larger cells which do not exist in mammals. [NIH] Melanoma: A form of skin cancer that arises in melanocytes, the cells that produce pigment. Melanoma usually begins in a mole. [NIH] Membrane: A very thin layer of tissue that covers a surface. [NIH] Membrane Lipids: Lipids, predominantly phospholipids, cholesterol and small amounts of glycolipids found in membranes including cellular and intracellular membranes. These lipids may be arranged in bilayers in the membranes with integral proteins between the layers and peripheral proteins attached to the outside. Membrane lipids are required for active transport, several enzymatic activities and membrane formation. [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]

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Menstruation: The normal physiologic discharge through the vagina of blood and mucosal tissues from the nonpregnant uterus. [NIH] Mental: Pertaining to the mind; psychic. 2. (L. mentum chin) pertaining to the chin. [EU] Mental Processes: Conceptual functions or thinking in all its forms. [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] Metallothionein: A low-molecular-weight (approx. 10 kD) protein occurring in the cytoplasm of kidney cortex and liver. It is rich in cysteinyl residues and contains no aromatic amino acids. Metallothionein shows high affinity for bivalent heavy metals. [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] Methotrexate: An antineoplastic antimetabolite with immunosuppressant properties. It is an inhibitor of dihydrofolate reductase and prevents the formation of tetrahydrofolate, necessary for synthesis of thymidylate, an essential component of DNA. [NIH] Microbe: An organism which cannot be observed with the naked eye; e. g. unicellular animals, lower algae, lower fungi, bacteria. [NIH] Microcirculation: The vascular network lying between the arterioles and venules; includes capillaries, metarterioles and arteriovenous anastomoses. Also, the flow of blood through this network. [NIH] Microglia: The third type of glial cell, along with astrocytes and oligodendrocytes (which together form the macroglia). Microglia vary in appearance depending on developmental stage, functional state, and anatomical location; subtype terms include ramified, perivascular, ameboid, resting, and activated. Microglia clearly are capable of phagocytosis and play an important role in a wide spectrum of neuropathologies. They have also been suggested to act in several other roles including in secretion (e.g., of cytokines and neural growth factors), in immunological processing (e.g., antigen presentation), and in central nervous system development and remodeling. [NIH] Microgram: A unit of mass (weight) of the metric system, being one-millionth of a gram (106 gm.) or one one-thousandth of a milligram (10-3 mg.). [EU] Micronuclei: Nuclei, separate from and additional to the main nucleus of a cell, produced during the telophase of mitosis or meiosis by lagging chromosomes or chromosome fragments derived from spontaneous or experimentally induced chromosomal structural changes. This concept also includes the smaller, reproductive nuclei found in multinucleate protozoans. [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] 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] Milligram: A measure of weight. A milligram is approximately 450,000-times smaller than a pound and 28,000-times smaller than an ounce. [NIH]

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Mineralocorticoids: A group of corticosteroids primarily associated with the regulation of water and electrolyte balance. This is accomplished through the effect on ion transport in renal tubules, resulting in retention of sodium and loss of potassium. Mineralocorticoid secretion is itself regulated by plasma volume, serum potassium, and angiotensin II. [NIH] Miotic: 1. Pertaining to, characterized by, or producing miosis : contraction of the pupil. 2. An agent that causes the pupil to contract. 3. Meiotic: characterized by cell division. [EU] Mitochondria: Parts of a cell where aerobic production (also known as cell respiration) takes place. [NIH] Mitochondrial Swelling: Increase in volume of mitochondria due to an influx of fluid; it occurs in hypotonic solutions due to osmotic pressure and in isotonic solutions as a result of altered permeability of the membranes of respiring mitochondria. [NIH] Mitomycin: An antineoplastic antibiotic produced by Streptomyces caespitosus. It acts as a bi- or trifunctional alkylating agent causing cross-linking of DNA and inhibition of DNA synthesis. [NIH] Mitosis: A method of indirect cell division by means of which the two daughter nuclei normally receive identical complements of the number of chromosomes of the somatic cells of the species. [NIH] Mitotic: Cell resulting from mitosis. [NIH] Mitotic inhibitors: Drugs that kill cancer cells by interfering with cell division (mitostis). [NIH]

Modeling: A treatment procedure whereby the therapist presents the target behavior which the learner is to imitate and make part of his repertoire. [NIH] Molecular: Of, pertaining to, or composed of molecules : a very small mass of matter. [EU] 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] Monensin: An antiprotozoal agent produced by Streptomyces cinnamonensis. It exerts its effect during the development of first-generation trophozoites into first-generation schizonts within the intestinal epithelial cells. It does not interfere with hosts' development of acquired immunity to the majority of coccidial species. Monensin is a sodium and proton selective ionophore and is widely used as such in biochemical studies. [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] Monocyte: A type of white blood cell. [NIH] Monocyte Chemoattractant Protein-1: A chemokine that is a chemoattractant for human monocytes and may also cause cellular activation of specific functions related to host defense. It is produced by leukocytes of both monocyte and lymphocyte lineage and by fibroblasts during tissue injury. [NIH] Mononuclear: A cell with one nucleus. [NIH] Monosomy: The condition in which one chromosome of a pair is missing. In a normally

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diploid cell it is represented symbolically as 2N-1. [NIH] Morphological: Relating to the configuration or the structure of live organs. [NIH] Morphology: The science of the form and structure of organisms (plants, animals, and other forms of life). [NIH] Motility: The ability to move spontaneously. [EU] Motion Sickness: Sickness caused by motion, as sea sickness, train sickness, car sickness, and air sickness. [NIH] Motor nerve: An efferent nerve conveying an impulse that excites muscular contraction. [NIH]

Mucinous: Containing or resembling mucin, the main compound in mucus. [NIH] Multidrug resistance: Adaptation of tumor cells to anticancer drugs in ways that make the drugs less effective. [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] 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] Muscular Diseases: Acquired, familial, and congenital disorders of skeletal muscle and smooth muscle. [NIH] Mutagenesis: Process of generating genetic mutations. It may occur spontaneously or be induced by mutagens. [NIH] Mutagens: Chemical agents that increase the rate of genetic mutation by interfering with the function of nucleic acids. A clastogen is a specific mutagen that causes breaks in chromosomes. [NIH] Myalgia: Pain in a muscle or muscles. [EU] Mydriatic: 1. Dilating the pupil. 2. Any drug that dilates the pupil. [EU] Myelin: The fatty substance that covers and protects nerves. [NIH] Myopathy: Any disease of a muscle. [EU] Myotonia: Prolonged failure of muscle relaxation after contraction. This may occur after voluntary contractions, muscle percussion, or electrical stimulation of the muscle. Myotonia is a characteristic feature of myotonic disorders. [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] Natural selection: A part of the evolutionary process resulting in the survival and reproduction of the best adapted individuals. [NIH] Nausea: An unpleasant sensation in the stomach usually accompanied by the urge to vomit. Common causes are early pregnancy, sea and motion sickness, emotional stress, intense

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pain, food poisoning, and various enteroviruses. [NIH] Necrolysis: Separation or exfoliation of tissue due to necrosis. [EU] 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] Neoplasms: New abnormal growth of tissue. Malignant neoplasms show a greater degree of anaplasia and have the properties of invasion and metastasis, compared to benign neoplasms. [NIH] Nephritis: Inflammation of the kidney; a focal or diffuse proliferative or destructive process which may involve the glomerulus, tubule, or interstitial renal tissue. [EU] Nephrogenic: Constant thirst and frequent urination because the kidney tubules cannot respond to antidiuretic hormone. The result is an increase in urine formation and excessive urine flow. [NIH] Nephrolithiasis: Kidney stones. [NIH] Nephropathy: Disease of the kidneys. [EU] Nephrosis: Descriptive histopathologic term for renal disease without an inflammatory component. [NIH] Nephrotic: Pertaining to, resembling, or caused by nephrosis. [EU] Nephrotic Syndrome: Clinical association of heavy proteinuria, hypoalbuminemia, and generalized edema. [NIH] Nephrotoxic: Toxic or destructive to kidney cells. [EU] Nerve Fibers: Slender processes of neurons, especially the prolonged axons that conduct nerve impulses. [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] Neural: 1. Pertaining to a nerve or to the nerves. 2. Situated in the region of the spinal axis, as the neutral arch. [EU] 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] Neuromuscular: Pertaining to muscles and nerves. [EU] Neuronal: Pertaining to a neuron or neurons (= conducting cells of the nervous system). [EU] Neurons: The basic cellular units of nervous tissue. Each neuron consists of a body, an axon, and dendrites. Their purpose is to receive, conduct, and transmit impulses in the nervous system. [NIH] Neuropathy: A problem in any part of the nervous system except the brain and spinal cord.

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Neuropathies can be caused by infection, toxic substances, or disease. [NIH] Neurophysiology: The scientific discipline concerned with the physiology of the nervous system. [NIH] Neurotoxicity: The tendency of some treatments to cause damage to the nervous system. [NIH]

Neurotransmitter: Any of a group of substances that are released on excitation from the axon terminal of a presynaptic neuron of the central or peripheral nervous system and travel across the synaptic cleft to either excite or inhibit the target cell. Among the many substances that have the properties of a neurotransmitter are acetylcholine, norepinephrine, epinephrine, dopamine, glycine, y-aminobutyrate, glutamic acid, substance P, enkephalins, endorphins, and serotonin. [EU] Neurotrophin 3: A neurotrophic factor involved in regulating the survival of visceral and proprioceptive sensory neurons. It is closely homologous to nerve growth factor beta and brain-derived neurotrophic factor. [NIH] Neurotrophins: A nerve growth factor. [NIH] 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] Neutropenia: An abnormal decrease in the number of neutrophils, a type of white blood cell. [NIH] Neutrophil: A type of white blood cell. [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] Nocodazole: Nocodazole is an antineoplastic agent which exerts its effect by depolymerizing microtubules. [NIH] Nonverbal Communication: Transmission of emotions, ideas, and attitudes between individuals in ways other than the spoken language. [NIH] Norepinephrine: Precursor of epinephrine that is secreted by the adrenal medulla and is a widespread central and autonomic neurotransmitter. Norepinephrine is the principal transmitter of most postganglionic sympathetic fibers and of the diffuse projection system in the brain arising from the locus ceruleus. It is also found in plants and is used pharmacologically as a sympathomimetic. [NIH] 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] Nuclear Envelope: The membrane system of the cell nucleus that surrounds the nucleoplasm. It consists of two concentric membranes separated by the perinuclear space. The structures of the envelope where it opens to the cytoplasm are called the nuclear pores (nuclear pore). [NIH] Nuclear Pore: An opening through the nuclear envelope formed by the nuclear pore complex which transports nuclear proteins or RNA into or out of the cell nucleus and which, under some conditions, acts as an ion channel. [NIH] Nuclear Proteins: Proteins found in the nucleus of a cell. Do not confuse with nucleoproteins which are proteins conjugated with nucleic acids, that are not necessarily

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present in the nucleus. [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] Nucleus: A body of specialized protoplasm found in nearly all cells and containing the chromosomes. [NIH] Nutritional Support: The administration of nutrients for assimilation and utilization by a patient by means other than normal eating. It does not include fluid therapy which normalizes body fluids to restore water-electrolyte balance. [NIH] Olfactory Bulb: Ovoid body resting on the cribriform plate of the ethmoid bone where the olfactory nerve terminates. The olfactory bulb contains several types of nerve cells including the mitral cells, on whose dendrites the olfactory nerve synapses, forming the olfactory glomeruli. The accessory olfactory bulb, which receives the projection from the vomeronasal organ via the vomeronasal nerve, is also included here. [NIH] Olfactory Nerve: The 1st cranial nerve. The olfactory nerve conveys the sense of smell. It is formed by the axons of olfactory receptor neurons which project from the olfactory epithelium (in the nasal epithelium) to the olfactory bulb. [NIH] Oncogenic: Chemical, viral, radioactive or other agent that causes cancer; carcinogenic. [NIH] Oncology: The study of cancer. [NIH] Oocytes: Female germ cells in stages between the prophase of the first maturation division and the completion of the second maturation division. [NIH] Open Reading Frames: Reading frames where successive nucleotide triplets can be read as codons specifying amino acids and where the sequence of these triplets is not interrupted by stop codons. [NIH] Ophthalmic: Pertaining to the eye. [EU] Ophthalmology: A surgical specialty concerned with the structure and function of the eye and the medical and surgical treatment of its defects and diseases. [NIH] Opsin: A protein formed, together with retinene, by the chemical breakdown of metarhodopsin. [NIH] Optic Chiasm: The X-shaped structure formed by the meeting of the two optic nerves. At the optic chiasm the fibers from the medial part of each retina cross to project to the other side of the brain while the lateral retinal fibers continue on the same side. As a result each half of the brain receives information about the contralateral visual field from both eyes. [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] Orderly: A male hospital attendant. [NIH] Organelles: Specific particles of membrane-bound organized living substances present in eukaryotic cells, such as the mitochondria; the golgi apparatus; endoplasmic reticulum;

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lysomomes; plastids; and vacuoles. [NIH] Osteoarthritis: A progressive, degenerative joint disease, the most common form of arthritis, especially in older persons. The disease is thought to result not from the aging process but from biochemical changes and biomechanical stresses affecting articular cartilage. In the foreign literature it is often called osteoarthrosis deformans. [NIH] Osteoporosis: Reduction of bone mass without alteration in the composition of bone, leading to fractures. Primary osteoporosis can be of two major types: postmenopausal osteoporosis and age-related (or senile) osteoporosis. [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] Overdose: An accidental or deliberate dose of a medication or street drug that is in excess of what is normally used. [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]

Oxygen Consumption: The oxygen consumption is determined by calculating the difference between the amount of oxygen inhaled and exhaled. [NIH] Pachymeningitis: Inflammation of the dura mater of the brain, the spinal cord or the optic nerve. [NIH] Paclitaxel: Antineoplastic agent isolated from the bark of the Pacific yew tree, Taxus brevifolia. Paclitaxel stabilizes microtubules in their polymerized form and thus mimics the action of the proto-oncogene proteins c-mos. [NIH] Palliative: 1. Affording relief, but not cure. 2. An alleviating medicine. [EU] 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] Pancytopenia: Deficiency of all three cell elements of the blood, erythrocytes, leukocytes and platelets. [NIH] Paralysis: Loss of ability to move all or part of the body. [NIH] Paraparesis: Mild to moderate loss of bilateral lower extremity motor function, which may be a manifestation of spinal cord diseases; peripheral nervous system diseases; muscular diseases; intracranial hypertension; parasagittal brain lesions; and other conditions. [NIH] Parathyroid: 1. Situated beside the thyroid gland. 2. One of the parathyroid glands. 3. A sterile preparation of the water-soluble principle(s) of the parathyroid glands, ad-ministered parenterally as an antihypocalcaemic, especially in the treatment of acute hypoparathyroidism with tetany. [EU] Parathyroid Glands: Two small paired endocrine glands in the region of the thyroid gland. They secrete parathyroid hormone and are concerned with the metabolism of calcium and phosphorus. [NIH]

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Parathyroid hormone: A substance made by the parathyroid gland that helps the body store and use calcium. Also called parathormone, parathyrin, or PTH. [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] Parkinsonism: A group of neurological disorders characterized by hypokinesia, tremor, and muscular rigidity. [EU] Parotid: The space that contains the parotid gland, the facial nerve, the external carotid artery, and the retromandibular vein. [NIH] Paroxysmal: Recurring in paroxysms (= spasms or seizures). [EU] Pathogen: Any disease-producing microorganism. [EU] Pathologic: 1. Indicative of or caused by a morbid condition. 2. Pertaining to pathology (= branch of medicine that treats the essential nature of the disease, especially the structural and functional changes in tissues and organs of the body caused by the disease). [EU] Pathologic Processes: The abnormal mechanisms and forms involved in the dysfunctions of tissues and organs. [NIH] Pathophysiology: Altered functions in an individual or an organ due to disease. [NIH] Pemphigus: Group of chronic blistering diseases characterized histologically by acantholysis and blister formation within the epidermis. [NIH] Penicillamine: 3-Mercapto-D-valine. The most characteristic degradation product of the penicillin antibiotics. It is used as an antirheumatic and as a chelating agent in Wilson's disease. [NIH] Penicillin: An antibiotic drug used to treat infection. [NIH] Penicillin V: A broad-spectrum penicillin antibiotic used orally in the treatment of mild to moderate infections by susceptible gram-positive organisms. [NIH] Peptide: Any compound consisting of two or more amino acids, the building blocks of proteins. Peptides are combined to make proteins. [NIH] Peptide Chain Elongation: The process whereby an amino acid is joined through a substituted amide linkage to a chain of peptides. [NIH] Peptide Fragments: Partial proteins formed by partial hydrolysis of complete proteins. [NIH] Perennial: Lasting through the year of for several years. [EU] Pericarditis: Inflammation of the pericardium. [EU] Pericardium: The fibroserous sac surrounding the heart and the roots of the great vessels. [NIH]

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] Peripheral Nervous System Diseases: Diseases of the peripheral nerves external to the brain and spinal cord, which includes diseases of the nerve roots, ganglia, plexi, autonomic nerves, sensory nerves, and motor nerves. [NIH] Peripheral Neuropathy: Nerve damage, usually affecting the feet and legs; causing pain, numbness, or a tingling feeling. Also called "somatic neuropathy" or "distal sensory

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polyneuropathy." [NIH] Peritoneal: Having to do with the peritoneum (the tissue that lines the abdominal wall and covers most of the organs in the abdomen). [NIH] Peritoneal Cavity: The space enclosed by the peritoneum. It is divided into two portions, the greater sac and the lesser sac or omental bursa, which lies behind the stomach. The two sacs are connected by the foramen of Winslow, or epiploic foramen. [NIH] Peritoneal Dialysis: Dialysis fluid being introduced into and removed from the peritoneal cavity as either a continuous or an intermittent procedure. [NIH] Peritoneum: Endothelial lining of the abdominal cavity, the parietal peritoneum covering the inside of the abdominal wall and the visceral peritoneum covering the bowel, the mesentery, and certain of the organs. The portion that covers the bowel becomes the serosal layer of the bowel wall. [NIH] Peroneal Nerve: The lateral of the two terminal branches of the sciatic nerve. The peroneal (or fibular) nerve provides motor and sensory innervation to parts of the leg and foot. [NIH] Peroxidase: A hemeprotein from leukocytes. Deficiency of this enzyme leads to a hereditary disorder coupled with disseminated moniliasis. It catalyzes the conversion of a donor and peroxide to an oxidized donor and water. EC 1.11.1.7. [NIH] Peroxide: Chemical compound which contains an atom group with two oxygen atoms tied to each other. [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] Phagocyte: An immune system cell that can surround and kill microorganisms and remove dead cells. Phagocytes include macrophages. [NIH] Phagocytosis: The engulfing of microorganisms, other cells, and foreign particles by phagocytic cells. [NIH] Phallic: Pertaining to the phallus, or penis. [EU] 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] 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] Phorbol: Class of chemicals that promotes the development of tumors. [NIH] Phospholipases: A class of enzymes that catalyze the hydrolysis of phosphoglycerides or glycerophosphatidates. EC 3.1.-. [NIH]

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Phospholipids: Lipids containing one or more phosphate groups, particularly those derived from either glycerol (phosphoglycerides; glycerophospholipids) or sphingosine (sphingolipids). They are polar lipids that are of great importance for the structure and function of cell membranes and are the most abundant of membrane lipids, although not stored in large amounts in the system. [NIH] 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] Physiologic: Having to do with the functions of the body. When used in the phrase "physiologic age," it refers to an age assigned by general health, as opposed to calendar age. [NIH]

Physiology: The science that deals with the life processes and functions of organismus, their cells, tissues, and organs. [NIH] Pigment: A substance that gives color to tissue. Pigments are responsible for the color of skin, eyes, and hair. [NIH] Pilocarpine: A slowly hydrolyzed muscarinic agonist with no nicotinic effects. Pilocarpine is used as a miotic and in the treatment of glaucoma. [NIH] Pilot study: The initial study examining a new method or treatment. [NIH] Pituitary Gland: A small, unpaired gland situated in the sella turcica tissue. It is connected to the hypothalamus by a short stalk. [NIH] Placenta: A highly vascular fetal organ through which the fetus absorbs oxygen and other nutrients and excretes carbon dioxide and other wastes. It begins to form about the eighth day of gestation when the blastocyst adheres to the decidua. [NIH] 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] Plastids: Self-replicating cytoplasmic organelles of plant and algal cells that contain pigments and may synthesize and accumulate various substances. Plastids are used in phylogenetic studies. [NIH] Platelet Activating Factor: A phospholipid derivative formed by platelets, basophils, neutrophils, monocytes, and macrophages. It is a potent platelet aggregating agent and inducer of systemic anaphylactic symptoms, including hypotension, thrombocytopenia, neutropenia, and bronchoconstriction. [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]

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Platelet-Derived Growth Factor: Mitogenic peptide growth hormone carried in the alphagranules of platelets. It is released when platelets adhere to traumatized tissues. Connective tissue cells near the traumatized region respond by initiating the process of replication. [NIH] Platelets: A type of blood cell that helps prevent bleeding by causing blood clots to form. Also called thrombocytes. [NIH] Plexus: A network or tangle; a general term for a network of lymphatic vessels, nerves, or veins. [EU] Pneumonia: Inflammation of the lungs. [NIH] Podophyllotoxin: The main active constituent of the resin from the roots of may apple or mandrake (Podophyllum peltatum and P. emodi). It is a potent spindle poison, toxic if taken internally, and has been used as a cathartic. It is very irritating to skin and mucous membranes, has keratolytic actions, has been used to treat warts and keratoses, and may have antineoplastic properties, as do some of its congeners and derivatives. [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 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] 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] Polyp: A growth that protrudes from a mucous membrane. [NIH] 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] Polyuria: Urination of a large volume of urine with an increase in urinary frequency, commonly seen in diabetes. [NIH] Portal Hypertension: High blood pressure in the portal vein. This vein carries blood into the liver. Portal hypertension is caused by a blood clot. This is a common complication of cirrhosis. [NIH] Portal Vein: A short thick vein formed by union of the superior mesenteric vein and the splenic vein. [NIH] Posterior: Situated in back of, or in the back part of, or affecting the back or dorsal surface of the body. In lower animals, it refers to the caudal end of the body. [EU] Postmenopausal: Refers to the time after menopause. Menopause is the time in a woman's life when menstrual periods stop permanently; also called "change of life." [NIH] Postnatal: Occurring after birth, with reference to the newborn. [EU] Postpericardiotomy Syndrome: A febrile illness associated with pericardial and sometimes pleuropulmonary reaction that often follows extensive pericardiotomy. [NIH] Postsynaptic: Nerve potential generated by an inhibitory hyperpolarizing stimulation. [NIH] Potassium: An element that is in the alkali group of metals. It has an atomic symbol K,

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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] Potentiates: A degree of synergism which causes the exposure of the organism to a harmful substance to worsen a disease already contracted. [NIH] Potentiation: An overall effect of two drugs taken together which is greater than the sum of the effects of each drug taken alone. [NIH] Practicability: A non-standard characteristic of an analytical procedure. It is dependent on the scope of the method and is determined by requirements such as sample throughout and costs. [NIH] Practice Guidelines: Directions or principles presenting current or future rules of policy for the health care practitioner to assist him in patient care decisions regarding diagnosis, therapy, or related clinical circumstances. The guidelines may be developed by government agencies at any level, institutions, professional societies, governing boards, or by the convening of expert panels. The guidelines form a basis for the evaluation of all aspects of health care and delivery. [NIH] Precipitation: The act or process of precipitating. [EU] Precursor: Something that precedes. In biological processes, a substance from which another, usually more active or mature substance is formed. In clinical medicine, a sign or symptom that heralds another. [EU] Prednisolone: A glucocorticoid with the general properties of the corticosteroids. It is the drug of choice for all conditions in which routine systemic corticosteroid therapy is indicated, except adrenal deficiency states. [NIH] Prednisone: A synthetic anti-inflammatory glucocorticoid derived from cortisone. It is biologically inert and converted to prednisolone in the liver. [NIH] Premedication: Preliminary administration of a drug preceding a diagnostic, therapeutic, or surgical procedure. The commonest types of premedication are antibiotics (antibiotic prophylaxis) and anti-anxiety agents. It does not include preanesthetic medication. [NIH] Prenatal: Existing or occurring before birth, with reference to the fetus. [EU] Presynaptic: Situated proximal to a synapse, or occurring before the synapse is crossed. [EU] 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] Primary Biliary Cirrhosis: A chronic liver disease. Slowly destroys the bile ducts in the liver. This prevents release of bile. Long-term irritation of the liver may cause scarring and cirrhosis in later stages of the disease. [NIH] Probe: An instrument used in exploring cavities, or in the detection and dilatation of strictures, or in demonstrating the potency of channels; an elongated instrument for exploring or sounding body cavities. [NIH] Progeny: The offspring produced in any generation. [NIH] Progesterone: Pregn-4-ene-3,20-dione. The principal progestational hormone of the body, secreted by the corpus luteum, adrenal cortex, and placenta. Its chief function is to prepare the uterus for the reception and development of the fertilized ovum. It acts as an antiovulatory agent when administered on days 5-25 of the menstrual cycle. [NIH] Progression: Increase in the size of a tumor or spread of cancer in the body. [NIH] Progressive: Advancing; going forward; going from bad to worse; increasing in scope or

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severity. [EU] Projection: A defense mechanism, operating unconsciously, whereby that which is emotionally unacceptable in the self is rejected and attributed (projected) to others. [NIH] 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] 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] Prosencephalon: The part of the brain developed from the most rostral of the three primary vesicles of the embryonic neural tube and consisting of the diencephalon and telencephalon. [NIH]

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 lower part of the pubic symphysis, above the deep layer of the triangular ligament, and rests upon the rectum. [NIH] Protease: Proteinase (= any enzyme that catalyses the splitting of interior peptide bonds in a protein). [EU]

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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 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 Synthesis Inhibitors: Compounds which inhibit the synthesis of proteins. They are usually antibiotics or toxins. Mechanism of the action of inhibition includes the interruption of peptide-chain elongation, the blocking the the A site of ribosomes, the misreading of the genetic code or the prevention of the attachment of oligosaccharide side chains to glycoproteins. [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] Proteinuria: The presence of protein in the urine, indicating that the kidneys are not working properly. [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] 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 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] Pruritus: An intense itching sensation that produces the urge to rub or scratch the skin to obtain relief. [NIH] Psoriasis: A common genetically determined, chronic, inflammatory skin disease characterized by rounded erythematous, dry, scaling patches. The lesions have a predilection for nails, scalp, genitalia, extensor surfaces, and the lumbosacral region. Accelerated epidermopoiesis is considered to be the fundamental pathologic feature in psoriasis. [NIH] Psychiatry: The medical science that deals with the origin, diagnosis, prevention, and treatment of mental disorders. [NIH] Psychoactive: Those drugs which alter sensation, mood, consciousness or other psychological or behavioral functions. [NIH] Psychology: The science dealing with the study of mental processes and behavior in man and animals. [NIH] Psychotherapy: A generic term for the treatment of mental illness or emotional disturbances primarily by verbal or nonverbal communication. [NIH]

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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] Pulmonary Edema: An accumulation of an excessive amount of watery fluid in the lungs, may be caused by acute exposure to dangerous concentrations of irritant gasses. [NIH] Pulmonary Fibrosis: Chronic inflammation and progressive fibrosis of the pulmonary alveolar walls, with steadily progressive dyspnea, resulting finally in death from oxygen lack or right heart failure. [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]

Puromycin: An antibiotic from Streptomyces alboniger that inhibits protein synthesis by binding to RNA. It is a antineoplastic and antitrypanosomal agent and is used in research as an inhibitor of protein synthesis. [NIH] Purpura: Purplish or brownish red discoloration, easily visible through the epidermis, caused by hemorrhage into the tissues. [NIH] Pustular: Pertaining to or of the nature of a pustule; consisting of pustules (= a visible collection of pus within or beneath the epidermis). [EU] 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] Quality of Life: A generic concept reflecting concern with the modification and enhancement of life attributes, e.g., physical, political, moral and social environment. [NIH] Quaternary: 1. Fourth in order. 2. Containing four elements or groups. [EU] 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] Racemic: Optically inactive but resolvable in the way of all racemic compounds. [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]

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Radiolabeled: Any compound that has been joined with a radioactive substance. [NIH] Radiotherapy: The use of ionizing radiation to treat malignant neoplasms and other benign conditions. The most common forms of ionizing radiation used as therapy are x-rays, gamma rays, and electrons. A special form of radiotherapy, targeted radiotherapy, links a cytotoxic radionuclide to a molecule that targets the tumor. When this molecule is an antibody or other immunologic molecule, the technique is called radioimmunotherapy. [NIH] Random Allocation: A process involving chance used in therapeutic trials or other research endeavor for allocating experimental subjects, human or animal, between treatment and control groups, or among treatment groups. It may also apply to experiments on inanimate objects. [NIH] Randomization: Also called random allocation. Is allocation of individuals to groups, e.g., for experimental and control regimens, by chance. Within the limits of chance variation, random allocation should make the control and experimental groups similar at the start of an investigation and ensure that personal judgment and prejudices of the investigator do not influence allocation. [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] 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] 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] Rectum: The last 8 to 10 inches of the large intestine. [NIH] Recurrence: The return of a sign, symptom, or disease after a remission. [NIH] Reductase: Enzyme converting testosterone to dihydrotestosterone. [NIH] Refer: To send or direct for treatment, aid, information, de decision. [NIH] Reflux: The term used when liquid backs up into the esophagus from the stomach. [NIH] Regimen: A treatment plan that specifies the dosage, the schedule, and the duration of treatment. [NIH] Relaxant: 1. Lessening or reducing tension. 2. An agent that lessens tension. [EU] Remission: A decrease in or disappearance of signs and symptoms of cancer. In partial remission, some, but not all, signs and symptoms of cancer have disappeared. In complete remission, all signs and symptoms of cancer have disappeared, although there still may be cancer in the body. [NIH] Renal cell carcinoma: A type of kidney cancer. [NIH] Renal failure: Progressive renal insufficiency and uremia, due to irreversible and progressive renal glomerular tubular or interstitial disease. [NIH] Renal pelvis: The area at the center of the kidney. Urine collects here and is funneled into

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the ureter, the tube that connects the kidney to the bladder. [NIH] Resection: Removal of tissue or part or all of an organ by surgery. [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] Respiratory Burst: A large increase in oxygen uptake by neutrophils and most types of tissue macrophages through activation of an NADPH-cytochrome b-dependent oxidase that reduces oxygen to a superoxide. Individuals with an inherited defect in which the oxidase that reduces oxygen to superoxide is decreased or absent (granulomatous disease, chronic) often die as a result of recurrent bacterial infections. [NIH] Respiratory Paralysis: Complete or severe weakness of the muscles of respiration. This condition may be associated with motor neuron diseases; peripheral nerve disorders; neuromuscular junction diseases; spinal cord diseases; injury to the phrenic nerve; and other disorders. [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] Retinoids: Derivatives of vitamin A. Used clinically in the treatment of severe cystic acne, psoriasis, and other disorders of keratinization. Their possible use in the prophylaxis and treatment of cancer is being actively explored. [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] Retrograde: 1. Moving backward or against the usual direction of flow. 2. Degenerating, deteriorating, or catabolic. [EU] Retrograde Amnesia: Amnesia extending backward, to include material antedating the onset of amnesia proper. [NIH] Retrospective: Looking back at events that have already taken place. [NIH] Retrovirus: A member of a group of RNA viruses, the RNA of which is copied during viral replication into DNA by reverse transcriptase. The viral DNA is then able to be integrated into the host chromosomal DNA. [NIH] Rhabdomyolysis: Necrosis or disintegration of skeletal muscle often followed by

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myoglobinuria. [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] Rhodopsin: A photoreceptor protein found in retinal rods. It is a complex formed by the binding of retinal, the oxidized form of retinol, to the protein opsin and undergoes a series of complex reactions in response to visible light resulting in the transmission of nerve impulses to the brain. [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] Rigidity: Stiffness or inflexibility, chiefly that which is abnormal or morbid; rigor. [EU] Risk factor: A habit, trait, condition, or genetic alteration that increases a person's chance of developing a disease. [NIH] Risk patient: Patient who is at risk, because of his/her behaviour or because of the type of person he/she is. [EU] Rods: One type of specialized light-sensitive cells (photoreceptors) in the retina that provide side vision and the ability to see objects in dim light (night vision). [NIH] Salicylic: A tuberculosis drug. [NIH] Saline: A solution of salt and water. [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] 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] Sciatic Nerve: A nerve which originates in the lumbar and sacral spinal cord (L4 to S3) and supplies motor and sensory innervation to the lower extremity. The sciatic nerve, which is the main continuation of the sacral plexus, is the largest nerve in the body. It has two major branches, the tibial nerve and the peroneal nerve. [NIH] Scleroderma: A chronic disorder marked by hardening and thickening of the skin. Scleroderma can be localized or it can affect the entire body (systemic). [NIH] Sclerosis: A pathological process consisting of hardening or fibrosis of an anatomical structure, often a vessel or a nerve. [NIH] Scopolamine: An alkaloid from Solanaceae, especially Datura metel L. and Scopola carniolica. Scopolamine and its quaternary derivatives act as antimuscarinics like atropine,

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but may have more central nervous system effects. Among the many uses are as an anesthetic premedication, in urinary incontinence, in motion sickness, as an antispasmodic, and as a mydriatic and cycloplegic. [NIH] Screening: Checking for disease when there are no symptoms. [NIH] Sebum: The oily substance secreted by sebaceous glands. It is composed of keratin, fat, and cellular debris. [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] Sedatives, Barbiturate: Those derivatives of barbituric or thiobarbituric acid that are used as hypnotics or sedatives. The structural class of all such derivatives, regardless of use, is barbiturates. [NIH] Sedimentation: The act of causing the deposit of sediment, especially by the use of a centrifugal machine. [EU] Segregation: The separation in meiotic cell division of homologous chromosome pairs and their contained allelomorphic gene pairs. [NIH] Seminiferous tubule: Tube used to transport sperm made in the testes. [NIH] Semisynthetic: Produced by chemical manipulation of naturally occurring substances. [EU] Senile: Relating or belonging to old age; characteristic of old age; resulting from infirmity of old 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] Sepsis: The presence of bacteria in the bloodstream. [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] Serrated: Having notches or teeth on the edge as a saw has. [NIH] Serum: The clear liquid part of the blood that remains after blood cells and clotting proteins have been removed. [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] 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

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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] Simvastatin: A derivative of lovastatin and potent competitive inhibitor of 3-hydroxy-3methylglutaryl coenzyme A reductase (hydroxymethylglutaryl CoA reductases), which is the rate-limiting enzyme in cholesterol biosynthesis. It may also interfere with steroid hormone production. Due to the induction of hepatic LDL receptors, it increases breakdown of LDL-cholesterol (lipoproteins, LDL cholesterol). [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] Skull: The skeleton of the head including the bones of the face and the bones enclosing the brain. [NIH] Small intestine: The part of the digestive tract that is located between the stomach and the large intestine. [NIH] Smooth muscle: Muscle that performs automatic tasks, such as constricting blood vessels. [NIH]

Sneezing: Sudden, forceful, involuntary expulsion of air from the nose and mouth caused by irritation to the mucous membranes of the upper respiratory tract. [NIH] 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] Solvent: 1. Dissolving; effecting a solution. 2. A liquid that dissolves or that is capable of dissolving; the component of a solution that is present in greater amount. [EU] Somatic: 1. Pertaining to or characteristic of the soma or body. 2. Pertaining to the body wall in contrast to the viscera. [EU] Somatic cells: All the body cells except the reproductive (germ) cells. [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]

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Specialist: In medicine, one who concentrates on 1 special branch of medical science. [NIH] Species: A taxonomic category subordinate to a genus (or subgenus) and superior to a subspecies or variety, composed of individuals possessing common characters distinguishing them from other categories of individuals of the same taxonomic level. In taxonomic nomenclature, species are designated by the genus name followed by a Latin or Latinized adjective or noun. [EU] Specificity: Degree of selectivity shown by an antibody with respect to the number and types of antigens with which the antibody combines, as well as with respect to the rates and the extents of these reactions. [NIH] Sperm: The fecundating fluid of the male. [NIH] Sperm Head: The anterior, usually ovoid, nucleus-containing part of spermatozoa. [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] 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 Diseases: Pathologic conditions which feature spinal cord damage or dysfunction, including disorders involving the meninges and perimeningeal spaces surrounding the spinal cord. Traumatic injuries, vascular diseases, infections, and inflammatory/autoimmune processes may affect the spinal cord. [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] Spinous: Like a spine or thorn in shape; having spines. [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] Splenomegaly: Enlargement of the spleen. [NIH] Spondylitis: Inflammation of the vertebrae. [EU] Sporadic: Neither endemic nor epidemic; occurring occasionally in a random or isolated manner. [EU] Squamous: Scaly, or platelike. [EU] Stabilization: The creation of a stable state. [EU] Steatosis: Fatty degeneration. [EU] Stellate: Star shaped. [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] 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]

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Steroid therapy: Treatment with corticosteroid drugs to reduce swelling, pain, and other symptoms of inflammation. [NIH] Stimulant: 1. Producing stimulation; especially producing stimulation by causing tension on muscle fibre through the nervous tissue. 2. An agent or remedy that produces stimulation. [EU]

Stimulus: That which can elicit or evoke action (response) in a muscle, nerve, gland or other excitable issue, or cause an augmenting action upon any function or metabolic process. [NIH] Stomach: An organ of digestion situated in the left upper quadrant of the abdomen between the termination of the esophagus and the beginning of the duodenum. [NIH] Stool: The waste matter discharged in a bowel movement; feces. [NIH] Stress: Forcibly exerted influence; pressure. Any condition or situation that causes strain or tension. Stress may be either physical or psychologic, or both. [NIH] Stroke: Sudden loss of function of part of the brain because of loss of blood flow. Stroke may be caused by a clot (thrombosis) or rupture (hemorrhage) of a blood vessel to the brain. [NIH] Structure-Activity Relationship: The relationship between the chemical structure of a compound and its biological or pharmacological activity. Compounds are often classed together because they have structural characteristics in common including shape, size, stereochemical arrangement, and distribution of functional groups. Other factors contributing to structure-activity relationship include chemical reactivity, electronic effects, resonance, and inductive effects. [NIH] Stupor: Partial or nearly complete unconsciousness, manifested by the subject's responding only to vigorous stimulation. Also, in psychiatry, a disorder marked by reduced responsiveness. [EU] 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] 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] Sulfinpyrazone: A uricosuric drug that is used to reduce the serum urate levels in gout therapy. It lacks anti-inflammatory, analgesic, and diuretic properties. [NIH] Superoxide: Derivative of molecular oxygen that can damage cells. [NIH] Superoxide Dismutase: An oxidoreductase that catalyzes the reaction between superoxide anions and hydrogen to yield molecular oxygen and hydrogen peroxide. The enzyme protects the cell against dangerous levels of superoxide. EC 1.15.1.1. [NIH] Supportive care: Treatment given to prevent, control, or relieve complications and side effects and to improve the comfort and quality of life of people who have cancer. [NIH]

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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] Suprachiasmatic Nucleus: An ovoid densely packed collection of small cells of the anterior hypothalamus lying close to the midline in a shallow impression of the optic chiasm. [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] Symptomatic: Having to do with symptoms, which are signs of a condition or disease. [NIH] Synapse: The region where the processes of two neurons come into close contiguity, and the nervous impulse passes from one to the other; the fibers of the two are intermeshed, but, according to the general view, there is no direct contiguity. [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] 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] 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] Systemic therapy: Treatment that uses substances that travel through the bloodstream, reaching and affecting cells all over the body. [NIH] Systolic: Indicating the maximum arterial pressure during contraction of the left ventricle of the heart. [EU] Telangiectasia: The permanent enlargement of blood vessels, causing redness in the skin or mucous membranes. [NIH] Telencephalon: Paired anteriolateral evaginations of the prosencephalon plus the lamina 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] Telomere: A terminal section of a chromosome which has a specialized structure and which is involved in chromosomal replication and stability. Its length is believed to be a few hundred base pairs. [NIH] Telophase: The final phase of cell division, in which two daughter nuclei are formed, the

Dictionary 191

cytoplasm divides, and the chromosomes lose their distinctness and are transformed into chromatin networks. [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] Temporal Lobe: Lower lateral part of the cerebral hemisphere. [NIH] Tendon: A discrete band of connective tissue mainly composed of parallel bundles of collagenous fibers by which muscles are attached, or two muscles bellies joined. [NIH] Terminalis: A groove on the lateral surface of the right atrium. [NIH] Testis: Either of the paired male reproductive glands that produce the male germ cells and the male hormones. [NIH] Tetany: 1. Hyperexcitability of nerves and muscles due to decrease in concentration of extracellular ionized calcium, which may be associated with such conditions as parathyroid hypofunction, vitamin D deficiency, and alkalosis or result from ingestion of alkaline salts; it is characterized by carpopedal spasm, muscular twitching and cramps, laryngospasm with inspiratory stridor, hyperreflexia and choreiform movements. 2. Tetanus. [EU] Thalidomide: A pharmaceutical agent originally introduced as a non-barbiturate hypnotic, but withdrawn from the market because of its known tetratogenic effects. It has been reintroduced and used for a number of immunological and inflammatory disorders. Thalidomide displays immunosuppresive and anti-angiogenic activity. It inhibits release of tumor necrosis factor alpha from monocytes, and modulates other cytokine action. [NIH] Therapeutics: The branch of medicine which is concerned with the treatment of diseases, palliative or curative. [NIH] Thoracic: Having to do with the chest. [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] 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] Thyroid: A gland located near the windpipe (trachea) that produces thyroid hormone, which helps regulate growth and metabolism. [NIH] Thyroid Gland: A highly vascular endocrine gland consisting of two lobes, one on either side of the trachea, joined by a narrow isthmus; it produces the thyroid hormones which are concerned in regulating the metabolic rate of the body. [NIH] Tibial Nerve: The medial terminal branch of the sciatic nerve. The tibial nerve fibers originate in lumbar and sacral spinal segments (L4 to S2). They supply motor and sensory innervation to parts of the calf and foot. [NIH] Tissue: A group or layer of cells that are alike in type and work together to perform a specific function. [NIH] Tomography: Imaging methods that result in sharp images of objects located on a chosen plane and blurred images located above or below the plane. [NIH]

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Topical: On the surface of the body. [NIH] Toxic: Having to do with poison or something harmful to the body. Toxic substances usually cause unwanted side effects. [NIH] Toxicity: The quality of being poisonous, especially the degree of virulence of a toxic microbe or of a poison. [EU] 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] Toxin: A poison; frequently used to refer specifically to a protein produced by some higher plants, certain animals, and pathogenic bacteria, which is highly toxic for other living organisms. Such substances are differentiated from the simple chemical poisons and the vegetable alkaloids by their high molecular weight and antigenicity. [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] 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] Transfusion: The infusion of components of blood or whole blood into the bloodstream. The blood may be donated from another person, or it may have been taken from the person earlier and stored until needed. [NIH] Translation: The process whereby the genetic information present in the linear sequence of ribonucleotides in mRNA is converted into a corresponding sequence of amino acids in a protein. It occurs on the ribosome and is unidirectional. [NIH] Translational: The cleavage of signal sequence that directs the passage of the protein through a cell or organelle membrane. [NIH] 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] Treatment Outcome: Evaluation undertaken to assess the results or consequences of management and procedures used in combating disease in order to determine the efficacy, effectiveness, safety, practicability, etc., of these interventions in individual cases or series. [NIH]

Tremor: Cyclical movement of a body part that can represent either a physiologic process or a manifestation of disease. Intention or action tremor, a common manifestation of cerebellar diseases, is aggravated by movement. In contrast, resting tremor is maximal when there is

Dictionary 193

no attempt at voluntary movement, and occurs as a relatively frequent manifestation of Parkinson disease. [NIH] Tricyclic: Containing three fused rings or closed chains in the molecular structure. [EU] Trifluralin: A microtubule-disrupting pre-emergence herbicide. [NIH] Trisomy: The possession of a third chromosome of any one type in an otherwise diploid cell. [NIH]

Trophic: Of or pertaining to nutrition. [EU] 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] Tuberculosis: Any of the infectious diseases of man and other animals caused by species of Mycobacterium. [NIH] Tubulin: A microtubule subunit protein found in large quantities in mammalian brain. It has also been isolated from sperm flagella, cilia, and other sources. Structurally, the protein is a dimer with a molecular weight of approximately 120,000 and a sedimentation coefficient of 5.8S. It binds to colchicine, vincristine, and vinblastine. [NIH] Tumor marker: A substance sometimes found in an increased amount in the blood, other body fluids, or tissues and which may mean that a certain type of cancer is in the body. Examples of tumor markers include CA 125 (ovarian cancer), CA 15-3 (breast cancer), CEA (ovarian, lung, breast, pancreas, and gastrointestinal tract cancers), and PSA (prostate cancer). Also called biomarker. [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] Tumour: 1. Swelling, one of the cardinal signs of inflammations; morbid enlargement. 2. A new growth of tissue in which the multiplication of cells is uncontrolled and progressive; called also neoplasm. [EU] Tunicamycin: An N-acetylglycosamine containing antiviral antibiotic obtained from Streptomyces lysosuperificus. It is also active against some bacteria and fungi, because it inhibits the glucosylation of proteins. Tunicamycin is used as tool in the study of microbial biosynthetic mechanisms. [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] 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] Untranslated Regions: The parts of the messenger RNA sequence that do not code for product, i.e. the 5' untranslated regions and 3' untranslated regions. [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]

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Uric: A kidney stone that may result from a diet high in animal protein. When the body breaks down this protein, uric acid levels rise and can form stones. [NIH] Uricosuric: 1. Pertaining to, characterized by, or promoting uricosuria (= the excretion of uric acid in the urine). 2. An agent that promotes uricosuria. [EU] Urinary: Having to do with urine or the organs of the body that produce and get rid of urine. [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] Ursodeoxycholic Acid: An epimer of chenodeoxycholic acid. It is a mammalian bile acid found first in the bear and is apparently either a precursor or a product of chenodeoxycholate. Its administration changes the composition of bile and may dissolve gallstones. It is used as a cholagogue and choleretic. [NIH] 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] Vaccine: A substance or group of substances meant to cause the immune system to respond to a tumor or to microorganisms, such as bacteria or viruses. [NIH] Vacuoles: Any spaces or cavities within a cell. They may function in digestion, storage, secretion, or excretion. [NIH] Vagina: The muscular canal extending from the uterus to the exterior of the body. Also called the birth canal. [NIH] Vaginal: Of or having to do with the vagina, the birth canal. [NIH] Valine: A branched-chain essential amino acid that has stimulant activity. It promotes muscle growth and tissue repair. It is a precursor in the penicillin biosynthetic pathway. [NIH]

Varicose: The common ulcer in the lower third of the leg or near the ankle. [NIH] Varicose Ulcer: Ulcer due to varicose veins. Chronic venous insufficiency in the deep veins of the legs leads to shunting the venous return into the superficial veins, in which pressure and flow rate, as well as oxygen content, are increased. [NIH] Vascular: Pertaining to blood vessels or indicative of a copious blood supply. [EU] 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] Venous: Of or pertaining to the veins. [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 body through the aorta. [NIH]

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Venules: The minute vessels that collect blood from the capillary plexuses and join together to form veins. [NIH] Verapamil: A calcium channel blocker that is a class IV anti-arrhythmia agent. [NIH] Vertebrae: A bony unit of the segmented spinal column. [NIH] Veterinary Medicine: The medical science concerned with the prevention, diagnosis, and treatment of diseases in animals. [NIH] Vibrio: A genus of Vibrionaceae, made up of short, slightly curved, motile, gram-negative rods. Various species produce cholera and other gastrointestinal disorders as well as abortion in sheep and cattle. [NIH] Vibrio cholerae: The etiologic agent of cholera. [NIH] Vinblastine: An anticancer drug that belongs to the family of plant drugs called vinca alkaloids. It is a mitotic inhibitor. [NIH] Vinca Alkaloids: A class of alkaloids from the genus of apocyanaceous woody herbs including periwinkles. They are some of the most useful antineoplastic agents. [NIH] Vincristine: An anticancer drug that belongs to the family of plant drugs called vinca alkaloids. [NIH] Viral: Pertaining to, caused by, or of the nature of virus. [EU] Viral vector: A type of virus used in cancer therapy. The virus is changed in the laboratory and cannot cause disease. Viral vectors produce tumor antigens (proteins found on a tumor cell) and can stimulate an antitumor immune response in the body. Viral vectors may also be used to carry genes that can change cancer cells back to normal cells. [NIH] 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] Visceral: , from viscus a viscus) pertaining to a viscus. [EU] 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] Vomeronasal Organ: A specialized part of the olfactory system located anteriorly in the nasal cavity within the nasal septum. Chemosensitive cells of the vomeronasal organ project via the vomeronasal nerve to the accessory olfactory bulb. The primary function of this organ appears to be in sensing pheromones which regulate reproductive and other social behaviors. While the structure has been thought absent in higher primate adults, data now suggests it may be present in adult humans. [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]

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Withdrawal: 1. A pathological retreat from interpersonal contact and social involvement, as may occur in schizophrenia, depression, or schizoid avoidant and schizotypal personality disorders. 2. (DSM III-R) A substance-specific organic brain syndrome that follows the cessation of use or reduction in intake of a psychoactive substance that had been regularly used to induce a state of intoxication. [EU] Wound Healing: Restoration of integrity to traumatized tissue. [NIH] Wound Infection: Invasion of the site of trauma by pathogenic microorganisms. [NIH] Xanthine: An urinary calculus. [NIH] Xanthine Oxidase: An iron-molybdenum flavoprotein containing FAD that oxidizes hypoxanthine, some other purines and pterins, and aldehydes. Deficiency of the enzyme, an autosomal recessive trait, causes xanthinuria. EC 1.1.3.22. [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] X-ray therapy: The use of high-energy radiation from x-rays to kill cancer cells and shrink tumors. Radiation may come from a machine outside the body (external-beam radiation therapy) or from materials called radioisotopes. Radioisotopes produce radiation and can be placed in or near the tumor or in the area near cancer cells. This type of radiation treatment is called internal radiation therapy, implant radiation, interstitial radiation, or brachytherapy. Systemic radiation therapy uses a radioactive substance, such as a radiolabeled monoclonal antibody, that circulates throughout the body. X-ray therapy is also called radiation therapy, radiotherapy, and irradiation. [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] 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]

197

INDEX A Abdomen, 131, 140, 164, 166, 176, 188, 189 Abdominal, 4, 97, 131, 164, 174, 176 Abdominal Pain, 97, 131, 164 Acantholysis, 131, 175 Acatalasia, 131, 142 Acetaldehyde, 15, 131 Acetylcholine, 131, 154, 172 Acidosis, 49, 131 Acne, 42, 131, 184 Acne Vulgaris, 42, 131 Acrylamide, 37, 76, 131 Acrylonitrile, 131 Adaptability, 131, 142 Adenine, 91, 131, 132 Adenocarcinoma, 81, 131, 159 Adenoma, 33, 131 Adenosine, 132, 165, 177 Adenylate Cyclase, 132, 143 Adrenal Cortex, 132, 147, 153, 179 Adrenal Glands, 132, 134 Adrenal Medulla, 132, 153, 172 Adrenergic, 8, 9, 10, 132, 150, 153, 190 Adverse Effect, 132, 186 Afferent, 16, 132, 154 Affinity, 21, 132, 137, 168, 187 Agar, 132, 145, 177 Agarose, 49, 132 Agonist, 7, 8, 9, 10, 12, 132, 150, 177 Airway, 7, 8, 9, 69, 132 Albuterol, 8, 9, 10, 132 Algorithms, 132, 139 Alimentary, 54, 65, 67, 132, 175 Alkaline, 131, 132, 141, 191 Alkaloid, 89, 90, 133, 137, 141, 145, 149, 160, 185 Alleles, 133, 160 Allergen, 133, 149, 186 Allergic Rhinitis, 55, 133, 159 Allopurinol, 4, 57, 58, 133 Alopecia, 133, 148 Alternative medicine, 106, 133 Alum, 133, 145 Amine, 133, 160 Amino Acid Sequence, 133, 135, 154, 157 Amino Acids, 133, 153, 157, 168, 173, 175, 178, 181, 185, 192 Amnesia, 13, 23, 133, 184

Amphetamines, 133, 145 Ampulla, 133, 143 Amyloid, 4, 38, 40, 133 Amyloidosis, 4, 31, 51, 52, 56, 59, 60, 61, 64, 133 Anaesthesia, 134, 162 Anal, 134, 155 Analgesic, 25, 134, 189 Analog, 134, 156 Analogous, 134, 151, 178, 192 Anaphylactic, 134, 177 Anaphylatoxins, 134, 146 Anaphylaxis, 46, 134 Anatomical, 16, 134, 162, 168, 185 Androgens, 132, 134, 147 Anesthesia, 96, 132, 134, 147, 152 Anesthetics, 96, 134, 138, 153 Aneuploidy, 12, 134 Angioplasty, 47, 134 Animal model, 21, 102, 134 Anionic, 17, 135 Anions, 91, 135, 164, 189 Anisotropy, 135, 155 Anode, 135 Anterograde, 23, 135 Antiallergic, 135, 147 Antibacterial, 15, 25, 135 Antibiotic, 135, 140, 144, 148, 150, 153, 158, 169, 175, 179, 182, 193 Antibodies, 11, 12, 17, 50, 101, 135, 159, 160, 177 Antibody, 7, 26, 132, 135, 145, 155, 159, 160, 161, 162, 164, 165, 167, 169, 182, 183, 186, 188, 196 Antibody-Dependent Cell Cytotoxicity, 135, 165 Anticholinergic, 13, 135 Anticoagulant, 135, 181 Anticonvulsants, 135 Antidiuretic, 135, 171 Antifungal, 11, 135, 158 Antigen, 90, 91, 132, 134, 135, 145, 155, 160, 161, 162, 167, 168, 186 Antigen-Antibody Complex, 135, 145 Anti-infective, 97, 136, 160 Anti-inflammatory, 7, 15, 89, 97, 136, 137, 147, 157, 179, 189

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Anti-Inflammatory Agents, 89, 136, 137, 147 Antimetabolite, 136, 156, 168 Antimicrobial, 91, 136 Antimitotic, 25, 37, 41, 63, 92, 99, 136 Antineoplastic, 90, 136, 147, 148, 149, 150, 156, 168, 169, 172, 174, 178, 182, 195 Antineoplastic Agents, 136, 195 Antioxidant, 136, 137 Antiphlogistic, 89, 136 Antiproliferative, 30, 89, 90, 99, 136 Antispasmodic, 136, 186 Antitubercular Agents, 14, 136 Antiviral, 136, 153, 163, 193 Anus, 134, 136, 145, 155 Aphthous Stomatitis, 58, 65, 136 Aplasia, 52, 136 Apolipoproteins, 136, 157 Aponeurosis, 136, 156 Apoptosis, 12, 23, 45, 79, 136, 148 Aqueous, 136, 138, 148, 152, 160 Arachidonic Acid, 136, 180 Arterial, 7, 137, 140, 161, 165, 181, 190 Arteries, 137, 140, 147 Arterioles, 137, 140, 141, 168 Artery, 134, 137, 152, 175, 182 Articular, 4, 137, 166, 174 Asbestos, 137 Asbestosis, 53, 137 Ascites, 4, 102, 137 Ascorbic Acid, 91, 137, 161 Aspartate, 5, 137 Aspirin, 64, 137 Assay, 15, 24, 30, 48, 80, 137 Astrocytes, 67, 137, 168 Asymptomatic, 103, 131, 137, 159 Atrophy, 131, 137, 153, 171 Atropine, 137, 185 Autoimmune disease, 101, 137, 170 Autonomic Nervous System, 137, 175 Axilla, 138, 140 Axons, 19, 22, 138, 149, 171, 173, 182, 184 B Back Pain, 48, 69, 82, 138 Bacteria, 91, 135, 138, 144, 152, 155, 158, 159, 168, 186, 192, 193, 194 Bacterial Infections, 138, 158, 184 Bactericidal, 14, 26, 138, 153 Barbiturate, 138, 191 Basal cell carcinoma, 56, 138 Basal cells, 138 Basal Ganglia, 138, 140, 156, 161

Base, 131, 138, 157, 165, 182, 190, 191 Basophil, 138, 160 Benign, 131, 138, 156, 171, 183 Benomyl, 11, 138 Beta-Galactosidase, 21, 138 Beta-pleated, 133, 138 Bilateral, 138, 153, 174 Bile, 14, 101, 103, 138, 139, 143, 156, 164, 166, 179, 188, 194 Bile Acids, 138, 188 Bile Acids and Salts, 138 Bile duct, 101, 138, 139, 143, 179 Bile Pigments, 139, 165 Biliary, 6, 14, 103, 139, 141, 143 Binding agent, 55, 139 Binding Sites, 14, 78, 139 Bioassay, 7, 139 Bioavailability, 57, 139 Biochemical, 10, 16, 18, 21, 26, 37, 47, 72, 94, 103, 133, 136, 139, 169, 174, 186 Biogenesis, 85, 139 Biological response modifier, 139, 163 Biological therapy, 139, 158 Biological Transport, 139, 149 Biomarkers, 20, 139 Biopsy, 4, 5, 139 Biosynthesis, 137, 139, 166, 187 Biotechnology, 25, 28, 36, 102, 106, 115, 139 Biotin, 80, 139 Biotransformation, 139 Bivalent, 140, 168 Bladder, 140, 162, 170, 180, 184, 193, 194 Blister, 140, 175 Bloating, 97, 140, 164 Blood Coagulation, 140, 141, 191 Blood Platelets, 140, 186, 191 Blood pressure, 92, 100, 102, 103, 140, 161, 169, 178, 187 Blood vessel, 140, 141, 142, 152, 157, 164, 187, 189, 190, 191, 194 Body Fluids, 3, 59, 139, 140, 151, 155, 173, 187, 193 Bone Marrow, 140, 145, 148, 161, 166, 187 Bowel, 97, 134, 140, 163, 164, 176, 189 Brachial, 22, 140 Brachial Plexus, 22, 140 Brachytherapy, 140, 163, 164, 182, 196 Brain Hypoxia, 140 Brain Infarction, 140 Brain Ischemia, 7, 140 Breeding, 93, 94, 140

199

Broad-spectrum, 140, 175 Bronchi, 141, 153 Bronchial, 141, 160 Bronchiseptica, 141, 176 Bronchoconstriction, 141, 177 Bullous, 50, 67, 141 Bupivacaine, 96, 141 C Calcium, 21, 77, 137, 141, 145, 174, 175, 187, 191, 195 Calculi, 141, 158 Callus, 141, 152 Camptothecin, 99, 141 Capillary, 7, 141, 195 Capsaicin, 55, 141 Carbohydrate, 141, 147, 157, 158, 178 Carbon Dioxide, 141, 149, 155, 177, 184 Carcinogenic, 141, 163, 173, 188 Carcinoma, 33, 38, 59, 79, 80, 141 Cardiac, 30, 67, 141, 153, 156, 188 Cardiomyopathy, 90, 141 Cardiovascular, 4, 9, 42, 141, 186 Cardiovascular System, 4, 141 Carotene, 82, 142, 184 Case report, 29, 61, 79, 142 Catalase, 91, 131, 142 Catheterization, 134, 142 Cations, 142, 164 Cause of Death, 15, 142 Cell Cycle, 23, 142, 144, 148, 154, 181 Cell Death, 19, 37, 47, 88, 136, 142, 154, 171 Cell Differentiation, 142, 187 Cell Division, 17, 88, 89, 90, 92, 100, 138, 142, 154, 158, 163, 167, 168, 169, 177, 180, 186, 190 Cell membrane, 139, 142, 149, 154, 177 Cell proliferation, 65, 142, 156, 187 Cell Respiration, 142, 169, 184 Cell Survival, 142, 158 Central Nervous System, 22, 131, 133, 137, 142, 143, 145, 151, 156, 168, 170, 173, 186 Centromere, 11, 142 Cerebral, 19, 138, 140, 142, 143, 153, 155, 182, 187, 190, 191 Cerebral hemispheres, 138, 140, 142, 143, 190 Cerebral Palsy, 143, 187 Cerebrum, 142, 143, 190 Cervical, 140, 143 Chemotactic Factors, 56, 143, 146 Chemotaxis, 49, 143 Chemotherapeutic agent, 23, 143

Chemotherapy, 10, 86, 143 Chenodeoxycholic Acid, 143, 194 Chlorine, 90, 143 Chloroquine, 7, 143 Cholangitis, 32, 143 Cholecystokinin, 16, 143 Cholera, 16, 143, 195 Cholera Toxin, 16, 143 Choleretic, 14, 143, 194 Cholestasis, 14, 102, 143 Cholesterol, 40, 102, 138, 144, 157, 166, 167, 187, 188 Chorion, 144 Chorionic Villi, 53, 144 Chromatin, 92, 136, 144, 152, 166, 188, 191 Chromosomal, 11, 76, 92, 134, 144, 160, 168, 184, 190 Chromosome, 11, 37, 39, 93, 94, 134, 142, 144, 159, 168, 169, 186, 190, 193 Chromosome Segregation, 11, 144 Chronic Disease, 144, 165 Chronic renal, 34, 50, 144 Circadian, 16, 144 Circadian Rhythm, 16, 144 Cirrhosis, 4, 5, 6, 15, 20, 28, 49, 55, 66, 81, 102, 103, 144, 178, 179 CIS, 144, 184 Cisplatin, 99, 144 Clarithromycin, 30, 144 Clinical Medicine, 144, 179 Clinical trial, 6, 20, 102, 115, 144, 146, 148, 150, 181, 183 Cloning, 17, 102, 139, 144 Clubbing, 4, 144 Coca, 25, 145 Cocaine, 4, 145 Coenzyme, 137, 145, 155, 166, 187 Cofactor, 145, 181, 191 Colitis, 145, 163, 164 Collagen, 15, 60, 62, 95, 145, 155, 163, 180 Collapse, 12, 42, 134, 145 Colon, 44, 79, 80, 81, 145, 163, 164 Colony-Stimulating Factors, 145, 158 Combination Therapy, 102, 145 Complement, 94, 134, 135, 145, 146, 157, 186 Complementary and alternative medicine, 75, 83, 146 Complementary medicine, 75, 146 Computational Biology, 115, 146 Concentric, 146, 172 Concomitant, 4, 34, 63, 146

200

Colchicine

Cones, 146, 184 Congestion, 146, 153 Conjugated, 138, 143, 146, 148, 172 Connective Tissue, 137, 140, 145, 146, 155, 156, 158, 190, 191 Consciousness, 96, 134, 146, 149, 150, 159, 181 Consolidation, 23, 146 Constipation, 67, 68, 96, 97, 146, 164 Constriction, 146, 164, 194 Contracture, 4, 146 Contraindications, ii, 146 Controlled study, 38, 146 Coordination, 146, 170 Coronary, 47, 95, 147 Corpuscle, 147, 153 Cortex, 12, 147, 152, 155, 182 Cortical, 12, 18, 147, 182 Corticosteroid, 5, 8, 9, 10, 33, 58, 69, 147, 179, 189 Cortisol, 7, 8, 9, 10, 147 Cortisone, 147, 179 Cranial, 147, 154, 164, 173, 175 Creatine, 35, 147 Creatinine, 4, 147 Creatinine clearance, 4, 147 Cribriform, 147, 173 Crossing-over, 147, 183 Cryoglobulinemia, 37, 147 Cultured cells, 20, 147 Curare, 147, 170 Curative, 147, 191 Cutaneous, 4, 46, 50, 66, 148 Cyclic, 25, 46, 132, 148, 180 Cyclin, 79, 148 Cyclophosphamide, 51, 64, 148 Cyclosporine, 30, 44, 54, 148 Cysteine, 17, 148 Cysteinyl, 148, 168 Cystine, 148 Cytochrome, 33, 38, 148, 184 Cytochrome b, 148, 184 Cytokine, 39, 148, 191 Cytokinesis, 48, 148 Cytoplasm, 136, 142, 143, 148, 152, 166, 168, 172, 185, 191 Cytoskeleton, 12, 18, 24, 79, 88, 93, 94, 148, 168 Cytotoxic, 141, 148, 162, 183, 187 Cytotoxicity, 17, 35, 89, 95, 144, 148 D Daunorubicin, 148, 150

De novo, 95, 148 Decarboxylation, 149, 160 Degenerative, 149, 159, 174 Dehydration, 143, 149 Deletion, 136, 149 Demecolcine, 37, 79, 89, 149 Dementia, 19, 149 Demography, 102, 149 Demyelinating Diseases, 97, 149 Dendrites, 149, 171, 173, 182 Dendritic, 12, 149, 167, 184 Dentate Gyrus, 23, 27, 149, 160 Depolarization, 149, 187 Deprivation, 19, 149 Dermatosis, 39, 50, 67, 149 Desensitization, 61, 149, 162 Deuterium, 45, 149, 160 Deuterium Oxide, 45, 149 Diagnostic procedure, 87, 106, 149 Diarrhea, 149, 164 Diastolic, 149, 161 Diffusion, 22, 139, 149, 159, 162 Digestion, 132, 138, 140, 150, 164, 166, 189, 194 Dimerization, 38, 150 Diploid, 134, 150, 170, 177, 193 Direct, iii, 22, 109, 144, 150, 183, 190 Disease Progression, 64, 150 Disinfectant, 150, 153 Disposition, 69, 150 Dissociation, 26, 27, 37, 132, 150 Distal, 150, 165, 175 Diuretic, 150, 189 Dolastatin 10, 47, 150 Dopamine, 145, 150, 156, 172, 176 Dorsal, 85, 150, 178, 188 Dorsum, 150, 156 Dose-dependent, 17, 150 Double-blind, 28, 48, 65, 67, 150 Doxorubicin, 17, 41, 150 Drug Design, 15, 30, 150 Drug Interactions, 110, 151 Drug Resistance, 18, 41, 151 Drug Tolerance, 151 Duct, 133, 142, 151, 154, 166 Duodenum, 138, 151, 189 Dura mater, 151, 167, 174 Dyes, 133, 151 Dysplasia, 97, 151 Dyspnea, 151, 182 E Echinacea, 78, 151

201

Edema, 151, 164, 171 Effector, 17, 24, 131, 135, 145, 151, 165 Effector cell, 135, 151, 165 Efferent, 151, 154, 170 Efficacy, 6, 7, 8, 9, 10, 36, 38, 40, 42, 95, 103, 136, 151, 192 Elastin, 145, 151 Electrolysis, 135, 142, 151 Electrolyte, 147, 151, 155, 169, 173, 179, 187 Electrons, 136, 138, 151, 164, 174, 182, 183 Electrophoresis, 131, 152 Embolism, 40, 152 Embryo, 94, 142, 152, 162, 178 Embryogenesis, 93, 94, 152 Empirical, 97, 152 Emulsion, 152, 155 Endarterectomy, 134, 152 Endemic, 143, 152, 188 Endogenous, 26, 28, 150, 152, 192 Endothelial cell, 76, 152, 191 Endotoxin, 26, 152, 193 End-stage renal, 144, 152 Entorhinal Cortex, 152, 160 Environmental Health, 114, 116, 152 Enzymatic, 141, 142, 146, 152, 160, 167, 184 Eosinophilia, 63, 152 Eosinophils, 91, 152, 158 Epidemiological, 7, 153 Epidermal, 36, 66, 153, 165, 167 Epidermis, 131, 138, 140, 153, 165, 175, 182 Epinephrine, 89, 132, 150, 153, 172, 193 Epithelial, 40, 52, 78, 131, 139, 143, 153, 169 Epithelial Cells, 143, 153, 169 Epithelium, 18, 153, 156, 173 Erythema, 4, 68, 153, 194 Erythema Nodosum, 68, 153 Erythrocyte Membrane, 46, 153 Erythrocytes, 140, 153, 159, 174, 186 Erythromycin, 144, 153 Esophagus, 153, 183, 189 Estradiol, 13, 91, 100, 153 Estrogen, 14, 153 Ethanol, 15, 153 Ether, 24, 153 Ethidium, 92, 153 Ethmoid, 154, 173 Etoposide, 75, 99, 154 Eukaryotic Cells, 154, 162, 173 Evacuation, 146, 154 Exfoliation, 154, 171

Exocrine, 143, 154, 174 Exocytosis, 154, 160 Exogenous, 139, 152, 154 Exon, 19, 154 Expiration, 154, 184 External-beam radiation, 154, 164, 182, 196 Extracellular, 18, 133, 137, 146, 154, 155, 187, 191 Extracellular Matrix, 146, 154, 155 Extraction, 89, 154 Extremity, 140, 154, 165, 174, 185 F Facial, 154, 175 Facial Nerve, 154, 175 Family Planning, 115, 154 Fat, 136, 138, 140, 142, 147, 154, 166, 170, 186, 187 Fatigue, 102, 154, 159 Fatty acids, 155, 158, 180 Febrile, 155, 178 Feces, 146, 155, 189 Fibrinogen, 60, 155, 191 Fibroblasts, 60, 62, 95, 155, 163, 169 Fibronectin, 95, 155 Fibrosis, 15, 20, 36, 48, 101, 146, 155, 182, 185 Fissure, 149, 155 Fixation, 92, 155, 186 Flatulence, 97, 155 Flavopiridol, 79, 155 Fluid Therapy, 155, 173 Fluorescence, 11, 26, 30, 37, 47, 154, 155 Fluorescence Polarization, 47, 155 Fluorouracil, 80, 156, 166 Forearm, 140, 156 Fovea, 155, 156 Fractionation, 21, 156 Free Radicals, 91, 136, 150, 156 Fructose, 156, 158, 164 Fungicide, 138, 156 Fusaric Acid, 85, 156 G Galactosides, 138, 156 Gallbladder, 131, 139, 143, 156 Gallium, 59, 156 Ganglia, 85, 131, 156, 171, 175 Ganglion, 22, 156, 184 Gas, 141, 143, 149, 155, 156, 160, 164, 172 Gastric, 65, 66, 156, 160 Gastric Mucosa, 65, 66, 156 Gastrin, 16, 156, 160

202

Colchicine

Gastrointestinal, 5, 44, 76, 137, 143, 153, 155, 156, 186, 189, 193, 195 Gastrointestinal tract, 153, 155, 156, 186, 193 Gemfibrozil, 61, 157 Gene, 16, 20, 21, 27, 35, 41, 66, 79, 94, 102, 133, 139, 157, 166, 186 Gene Expression, 16, 22, 35, 79, 157 Genetic Code, 157, 173, 181 Genetic Engineering, 139, 144, 157 Genetics, 42, 65, 89, 93, 157 Genital, 157, 194 Genitourinary, 31, 157, 194 Genotype, 8, 9, 157, 176 Germ Cells, 157, 167, 173, 174, 188, 191 Gland, 72, 94, 102, 132, 147, 157, 174, 175, 177, 180, 186, 189, 191 Glomerular, 157, 164, 183 Glomeruli, 157, 173 Glomerulus, 157, 165, 171 Glottis, 157, 176 Glucocorticoid, 33, 157, 179 Glucose, 89, 137, 157, 158, 185 Glutathione Peroxidase, 91, 157 Glycerol, 157, 158, 177 Glycerophospholipids, 158, 177 Glycine, 18, 138, 143, 158, 172 Glycols, 158, 160 Glycoprotein, 27, 38, 39, 41, 54, 56, 79, 80, 155, 158, 190, 191, 193 Glycoside, 75, 158, 185 Gonadal, 158, 188 Gout, 3, 24, 38, 57, 58, 60, 69, 82, 88, 89, 90, 92, 94, 100, 120, 158, 189 Governing Board, 158, 179 Graft, 102, 158, 162 Gram-positive, 158, 175 Granulation Tissue, 95, 158 Granule, 27, 149, 158, 185 Granulocyte, 44, 68, 145, 158 Granulocyte Colony-Stimulating Factor, 68, 145, 158 Granulomatous Disease, Chronic, 158, 184 Griseofulvin, 11, 76, 158 Growth factors, 6, 15, 158, 168 Guanine, 158 Guanosine Triphosphate, 92, 158 H Haemodialysis, 63, 159 Half-Life, 14, 159 Haploid, 93, 94, 159, 177 Haptens, 132, 159

Hay Fever, 133, 159 Heart failure, 159, 182 Hemolysis, 153, 159 Hemorrhage, 159, 182, 189 Hemostasis, 159, 186 Hepatic, 4, 5, 14, 15, 32, 66, 102, 159, 166, 187 Hepatic Encephalopathy, 5, 159 Hepatitis, 5, 20, 28, 42, 57, 67, 159 Hepatitis C, 5, 20, 159 Hepatocellular, 20, 159 Hepatocellular carcinoma, 20, 159 Hepatocyte, 14, 143, 159 Herbicide, 159, 193 Hereditary, 51, 158, 159, 171, 176 Heredity, 131, 157, 159 Heterochromatin, 12, 159 Heterogeneity, 132, 159 Heterozygotes, 11, 160 Hippocampus, 12, 23, 149, 160, 182, 189 Histamine, 45, 46, 134, 160 Histamine Release, 46, 134, 160 Histidine, 160 Histones, 144, 160 Homoharringtonine, 25, 160 Homologous, 11, 133, 140, 147, 160, 172, 186, 190 Hormonal, 137, 147, 160 Hormone, 45, 139, 144, 147, 153, 156, 160, 167, 171, 178, 179, 185, 186, 187, 191 Hybridomas, 160, 163 Hydration, 131, 160 Hydrogen, 90, 91, 131, 133, 138, 141, 142, 149, 157, 160, 169, 172, 174, 181, 189 Hydrogen Peroxide, 91, 142, 157, 160, 189 Hydrolysis, 14, 90, 92, 100, 138, 140, 144, 160, 165, 175, 176, 178, 181 Hydroxides, 160 Hydroxyl Radical, 91, 160 Hydroxylysine, 145, 161 Hydroxyproline, 145, 161 Hyperbilirubinemia, 161, 164 Hypersensitivity, 75, 78, 133, 134, 149, 161, 185, 186 Hypertension, 4, 102, 161, 164, 178 Hyperuricemia, 4, 158, 161 Hypnotic, 138, 161, 191 Hypokinesia, 161, 175 Hypotension, 161, 177 Hypothalamic, 16, 161 Hypothalamus, 137, 161, 177, 190

203

I Idiopathic, 36, 46, 53, 58, 161 Imidazole, 139, 160, 161 Immune response, 133, 135, 137, 147, 159, 161, 186, 189, 195 Immune system, 139, 151, 161, 162, 167, 170, 176, 194, 195 Immunity, 161, 169 Immunization, 161, 162, 186 Immunocompromised, 10, 161 Immunodeficiency, 10, 98, 161 Immunologic, 143, 161, 183 Immunology, 32, 37, 42, 43, 53, 78, 132, 161 Immunosuppressant, 102, 156, 161, 168 Immunosuppression, 60, 161, 162, 166 Immunosuppressive, 97, 148, 157, 161, 162 Immunosuppressive Agents, 161, 162 Immunotherapy, 139, 149, 162 Impairment, 48, 95, 143, 162 Implant radiation, 162, 163, 164, 182, 196 In situ, 11, 30, 37, 162 In Situ Hybridization, 11, 30, 37, 162 In vitro, 12, 14, 22, 46, 49, 50, 64, 95, 162 In vivo, 12, 27, 47, 50, 66, 90, 91, 95, 162, 166 Incision, 162, 164 Incontinence, 162, 186 Incubation, 162, 165, 176 Incubation period, 162, 165, 176 Induction, 13, 17, 39, 47, 72, 93, 94, 134, 162, 187 Infertility, 21, 162 Infiltration, 7, 162 Inflammatory bowel disease, 62, 163 Ingestion, 34, 42, 76, 163, 178, 191 Inhalation, 137, 163, 178 Initiation, 17, 96, 163, 192 Innervation, 140, 154, 163, 176, 185, 191 Inorganic, 144, 160, 163 Insight, 18, 37, 163 Insulator, 97, 163, 170 Interferon, 20, 48, 62, 67, 78, 163 Interferon-alpha, 67, 163 Interleukin-1, 64, 163 Interleukin-2, 62, 163 Interleukin-6, 15, 163 Intermittent, 42, 63, 86, 155, 163, 176 Internal radiation, 163, 164, 182, 196 Interphase, 24, 159, 163 Interstitial, 3, 60, 102, 140, 163, 164, 171, 183, 196

Interstitial Collagenase, 60, 163 Intestinal, 16, 26, 142, 143, 164, 169 Intestinal Mucosa, 143, 164 Intestine, 138, 140, 164, 183, 187 Intoxication, 30, 49, 52, 55, 79, 164, 196 Intracellular, 21, 47, 92, 100, 162, 164, 167, 179, 180, 183, 186 Intracranial Hypertension, 164, 174 Intrahepatic, 14, 164 Intramuscular, 95, 164, 175 Intraocular, 89, 164 Intraocular pressure, 89, 164 Intravenous, 36, 44, 48, 61, 68, 69, 91, 96, 164, 175 Intrinsic, 16, 22, 132, 164 Inulin, 151, 164 Invasive, 20, 22, 161, 164 Ion Channels, 137, 164 Ions, 77, 90, 138, 150, 151, 160, 164, 169 Irradiation, 7, 164, 196 Irritable Bowel Syndrome, 97, 164 Ischemia, 6, 137, 140, 164 J Jaundice, 103, 161, 164 K Kb, 114, 165 Keratin, 165, 186 Keratinocytes, 27, 66, 165 Kidney Cortex, 165, 168 Kidney stone, 3, 165, 171, 194 Killer Cells, 91, 165 Kinesin, 75, 165 Kinetic, 165 L Labile, 92, 100, 145, 165 Leg Ulcer, 40, 165 Lentivirus, 98, 165 Lesion, 33, 165, 166, 193 Lethal, 17, 44, 138, 165 Lethargy, 97, 165 Leucocyte, 165 Leukaemia, 49, 165 Leukemia, 39, 89, 90, 150, 166 Levamisole, 53, 166 Ligaments, 147, 166 Ligands, 7, 166 Light microscope, 11, 166 Lipid, 136, 157, 166, 170 Liposomes, 17, 166 Liver Cirrhosis, 15, 24, 39, 65, 166 Liver Transplantation, 5, 6, 20, 166 Localization, 16, 19, 50, 96, 166

204

Colchicine

Localized, 19, 50, 96, 133, 140, 155, 162, 166, 177, 185, 193, 194 Locomotion, 92, 100, 166, 177 Lovastatin, 166, 187 Lumbar, 138, 166, 185, 191 Lymph, 143, 147, 152, 166 Lymphatic, 162, 166, 178, 187, 188 Lymphocyte Depletion, 162, 166 Lymphocytes, 30, 39, 43, 47, 49, 91, 135, 160, 161, 163, 165, 166, 167, 188, 195 Lymphocytic, 49, 167 Lymphoid, 135, 158, 165, 166, 167 Lymphoma, 39, 167 M Macrophage, 7, 14, 98, 135, 145, 163, 167 Malignant, 131, 136, 167, 171, 183 Malnutrition, 5, 137, 167 Medial, 23, 154, 167, 173, 191 Mediate, 14, 150, 165, 167 Mediator, 143, 163, 167, 186 MEDLINE, 115, 167 Meiosis, 11, 140, 144, 167, 168, 190, 193 Melanin, 167, 176, 193 Melanocytes, 167 Melanoma, 86, 167 Membrane Lipids, 167, 177 Membrane Proteins, 166, 167 Memory, 13, 23, 48, 133, 149, 167 Meninges, 142, 151, 167, 188 Meningitis, 41, 167 Menstruation, 42, 168 Mental, iv, 6, 114, 116, 149, 150, 154, 161, 167, 168, 181, 185, 193 Mental Processes, 150, 168, 181 Metabolic disorder, 158, 168 Metabolite, 26, 139, 166, 168 Metallothionein, 17, 168 Metaphase, 63, 88, 140, 168, 193 Methotrexate, 6, 29, 40, 64, 102, 103, 105, 168 Microbe, 168, 192 Microcirculation, 166, 168 Microglia, 137, 168 Microgram, 14, 168 Micronuclei, 37, 76, 168 Microorganism, 145, 168, 175, 195 Microscopy, 14, 131, 168 Microtubules, 10, 19, 24, 27, 45, 53, 55, 72, 76, 78, 88, 92, 100, 165, 168, 172, 174 Migration, 6, 31, 52, 95, 168 Milligram, 168 Mineralocorticoids, 132, 147, 169

Miotic, 169, 177 Mitochondria, 53, 169, 173 Mitochondrial Swelling, 169, 171 Mitomycin, 25, 76, 169 Mitosis, 23, 52, 75, 77, 88, 92, 100, 136, 144, 168, 169 Mitotic, 10, 24, 40, 88, 89, 90, 92, 100, 150, 154, 169, 195 Mitotic inhibitors, 150, 169 Modeling, 151, 169 Molecular Structure, 169, 193 Molecule, 21, 89, 135, 138, 139, 145, 146, 148, 150, 151, 158, 160, 169, 174, 183, 186, 192, 194 Monensin, 62, 169 Monitor, 14, 147, 169, 172 Monoclonal, 160, 164, 169, 182, 196 Monocyte, 7, 135, 169 Monocyte Chemoattractant Protein-1, 7, 169 Mononuclear, 169, 193 Monosomy, 134, 169 Morphological, 12, 19, 65, 152, 167, 170 Morphology, 12, 17, 19, 93, 170 Motility, 94, 95, 97, 170, 186 Motion Sickness, 170, 186 Motor nerve, 86, 170, 175 Mucinous, 156, 170 Multidrug resistance, 17, 27, 30, 38, 47, 57, 66, 79, 170 Multiple sclerosis, 88, 90, 97, 170 Muscle relaxant, 89, 170 Muscle Relaxation, 170 Muscle tension, 170 Muscular Diseases, 170, 174 Mutagenesis, 30, 37, 39, 57, 76, 94, 170 Mutagens, 170 Myalgia, 63, 170 Mydriatic, 170, 186 Myelin, 97, 149, 170 Myopathy, 29, 30, 34, 35, 49, 170 Myotonia, 34, 54, 170 N Narcotic, 131, 170 Natural selection, 139, 170 Nausea, 97, 170, 193 Necrolysis, 66, 171 Necrosis, 7, 136, 140, 171, 184 Neoplasms, 136, 137, 148, 171, 183 Nephritis, 72, 171 Nephrogenic, 16, 171 Nephrolithiasis, 3, 171

205

Nephropathy, 40, 41, 54, 171 Nephrosis, 171 Nephrotic, 4, 50, 59, 60, 61, 171 Nephrotic Syndrome, 4, 50, 59, 60, 61, 171 Nephrotoxic, 72, 171 Nerve Fibers, 97, 140, 171, 191 Nerve Growth Factor, 27, 171, 172 Nervous System, 18, 132, 137, 142, 167, 171, 172, 175, 190 Neural, 23, 72, 132, 133, 168, 171, 180 Neuroblastoma, 47, 171 Neurodegenerative Diseases, 67, 171 Neuroendocrine, 171, 190 Neuromuscular, 44, 92, 100, 131, 171, 184 Neuronal, 6, 12, 13, 20, 22, 37, 171 Neurons, 7, 12, 13, 16, 18, 19, 50, 55, 88, 145, 149, 156, 170, 171, 172, 173, 182, 190 Neuropathy, 72, 171, 175 Neurophysiology, 18, 149, 172 Neurotoxicity, 27, 55, 72, 172 Neurotransmitter, 131, 132, 150, 158, 160, 164, 172, 186, 189 Neurotrophin 3, 27, 172 Neurotrophins, 18, 172 Neutrons, 164, 172, 182 Neutropenia, 58, 172, 177 Neutrophil, 31, 49, 65, 172 Nitrogen, 132, 133, 134, 148, 155, 172, 193 Nocodazole, 23, 81, 172 Nonverbal Communication, 172, 181 Norepinephrine, 132, 150, 156, 172 Nuclear, 11, 24, 41, 47, 138, 141, 149, 152, 154, 156, 171, 172, 184 Nuclear Envelope, 11, 172 Nuclear Pore, 12, 172 Nuclear Proteins, 172 Nuclei, 151, 157, 160, 168, 169, 172, 173, 181, 190 Nucleic acid, 99, 154, 157, 162, 170, 172, 173 Nucleus, 13, 16, 136, 137, 144, 148, 149, 152, 154, 166, 167, 168, 169, 172, 173, 180, 181, 188 Nutritional Support, 5, 173 O Olfactory Bulb, 19, 173, 195 Olfactory Nerve, 19, 173 Oncogenic, 165, 173, 181 Oncology, 13, 23, 32, 89, 90, 173 Oocytes, 18, 173 Open Reading Frames, 165, 173 Ophthalmic, 89, 95, 173

Ophthalmology, 22, 36, 52, 62, 69, 155, 173 Opsin, 173, 184, 185 Optic Chiasm, 161, 173, 190 Optic Nerve, 173, 174, 184 Orderly, 144, 173 Organelles, 92, 100, 148, 165, 167, 173, 177 Osteoarthritis, 29, 82, 120, 174 Osteoporosis, 6, 102, 174 Ovary, 153, 174, 178 Overdose, 29, 32, 42, 43, 52, 56, 58, 66, 67, 68, 69, 174 Oxidation, 136, 140, 148, 157, 174 Oxygen Consumption, 27, 174, 184 P Pachymeningitis, 167, 174 Paclitaxel, 23, 72, 78, 79, 94, 95, 99, 174 Palliative, 174, 191 Palsy, 19, 174 Pancreas, 131, 139, 174, 193 Pancreatic, 143, 174 Pancytopenia, 68, 174 Paralysis, 147, 174, 187 Paraparesis, 98, 174 Parathyroid, 80, 174, 175, 191 Parathyroid Glands, 174 Parathyroid hormone, 80, 174, 175 Parenteral, 89, 175 Parkinsonism, 19, 175 Parotid, 72, 175 Paroxysmal, 175, 176, 195 Pathogen, 10, 162, 175 Pathologic, 131, 136, 139, 147, 161, 175, 181, 188, 194 Pathologic Processes, 136, 175 Pathophysiology, 15, 175 Pemphigus, 39, 131, 175 Penicillamine, 6, 53, 60, 94, 95, 175 Penicillin, 48, 175, 194 Penicillin V, 48, 175 Peptide, 6, 16, 18, 20, 21, 47, 143, 144, 165, 175, 178, 180, 181 Peptide Chain Elongation, 144, 175 Peptide Fragments, 18, 175 Perennial, 151, 175 Pericarditis, 55, 58, 59, 82, 175 Pericardium, 175, 190 Peripheral blood, 47, 163, 175 Peripheral Nervous System, 22, 149, 171, 172, 174, 175, 189 Peripheral Nervous System Diseases, 174, 175 Peripheral Neuropathy, 4, 175

206

Colchicine

Peritoneal, 30, 137, 176 Peritoneal Cavity, 137, 176 Peritoneal Dialysis, 30, 176 Peritoneum, 176 Peroneal Nerve, 176, 185 Peroxidase, 91, 176 Peroxide, 90, 91, 176 Pertussis, 37, 176, 195 Phagocyte, 63, 176 Phagocytosis, 27, 69, 91, 168, 176 Phallic, 155, 176 Pharmacokinetic, 176 Pharmacologic, 4, 134, 159, 176, 192 Phenotype, 13, 18, 90, 176 Phenylalanine, 176, 193 Phorbol, 25, 176 Phospholipases, 176, 187 Phospholipids, 102, 154, 167, 177 Phosphorus, 141, 174, 177 Phosphorylation, 12, 19, 177 Physiologic, 7, 132, 139, 159, 161, 164, 168, 177, 180, 183, 192 Physiology, 53, 72, 172, 177 Pigment, 52, 167, 177 Pilocarpine, 89, 177 Pilot study, 49, 177 Pituitary Gland, 147, 177 Placenta, 144, 153, 177, 179 Plaque, 134, 177 Plasma, 26, 63, 135, 142, 145, 155, 158, 159, 169, 177 Plasma cells, 135, 158, 177 Plastids, 174, 177 Platelet Activating Factor, 24, 177 Platelet Activation, 177, 187 Platelet-Derived Growth Factor, 53, 178 Platelets, 27, 174, 177, 178 Plexus, 140, 178, 185 Pneumonia, 146, 178 Podophyllotoxin, 154, 178 Poisoning, 34, 36, 44, 45, 56, 76, 164, 171, 178 Pollen, 11, 93, 178 Polymers, 19, 27, 178, 181 Polymorphic, 149, 178 Polyp, 33, 178 Polypeptide, 16, 21, 133, 145, 155, 178, 196 Polysaccharide, 132, 135, 178 Polyuria, 46, 178 Portal Hypertension, 4, 102, 103, 178 Portal Vein, 178 Posterior, 134, 138, 150, 174, 178

Postmenopausal, 174, 178 Postnatal, 85, 178 Postpericardiotomy Syndrome, 33, 178 Postsynaptic, 178, 187 Potassium, 53, 74, 77, 169, 178 Potentiates, 163, 179 Potentiation, 18, 179, 187 Practicability, 179, 192 Practice Guidelines, 116, 179 Precipitation, 21, 179 Precursor, 17, 137, 148, 150, 151, 152, 158, 172, 176, 179, 193, 194 Prednisolone, 179 Prednisone, 46, 179 Premedication, 179, 186 Prenatal, 152, 179 Presynaptic, 16, 172, 179, 190 Prevalence, 7, 8, 9, 65, 66, 179 Primary Biliary Cirrhosis, 6, 28, 29, 37, 39, 40, 44, 51, 54, 62, 64, 65, 88, 101, 103, 105, 179 Probe, 14, 18, 179 Progeny, 93, 179 Progesterone, 179, 188 Progression, 17, 134, 179 Progressive, 6, 19, 142, 144, 149, 151, 171, 174, 177, 179, 182, 183, 193 Projection, 16, 172, 173, 180, 182 Proline, 145, 161, 180 Prophase, 140, 173, 180, 190, 193 Prophylaxis, 51, 96, 179, 180, 184 Prosencephalon, 180, 190 Prospective Studies, 103, 180 Prospective study, 8, 9, 10, 180 Prostaglandin, 49, 180 Prostaglandins A, 180 Prostate, 139, 180, 193 Protease, 145, 180 Protein C, 5, 19, 133, 136, 165, 181 Protein S, 13, 93, 94, 95, 102, 139, 144, 153, 157, 181, 182, 185 Protein Synthesis Inhibitors, 93, 94, 181 Proteins, 17, 19, 20, 21, 26, 32, 97, 133, 135, 136, 139, 142, 144, 145, 148, 153, 160, 163, 165, 167, 169, 172, 175, 177, 178, 181, 183, 186, 192, 193, 195 Proteinuria, 4, 56, 171, 181 Proteolytic, 17, 145, 155, 181 Protocol, 61, 181 Protons, 160, 181, 182 Proto-Oncogene Proteins, 174, 181 Proto-Oncogene Proteins c-mos, 174, 181

207

Pruritus, 6, 102, 181 Psoriasis, 181, 184 Psychiatry, 15, 155, 181, 189 Psychoactive, 181, 196 Psychology, 97, 150, 181 Psychotherapy, 97, 181 Public Policy, 115, 182 Publishing, 4, 5, 26, 182 Pulmonary, 46, 53, 140, 143, 182, 194 Pulmonary Artery, 140, 182, 194 Pulmonary Edema, 143, 182 Pulmonary Fibrosis, 46, 53, 182 Pulse, 169, 182 Puromycin, 13, 182 Purpura, 40, 58, 64, 182 Pustular, 39, 131, 182 Pyramidal Cells, 149, 182 Q Quality of Life, 182, 189 Quaternary, 182, 185 R Race, 98, 132, 168, 182 Racemic, 98, 132, 182 Radiation, 13, 154, 155, 156, 162, 163, 164, 182, 183, 196 Radiation therapy, 154, 156, 163, 164, 182, 196 Radioactive, 159, 160, 162, 163, 164, 172, 173, 182, 183, 196 Radiolabeled, 19, 164, 182, 183, 196 Radiotherapy, 140, 164, 182, 183, 196 Random Allocation, 183 Randomization, 93, 183 Randomized, 20, 28, 29, 39, 49, 54, 67, 151, 183 Reagent, 143, 183 Receptor, 7, 8, 9, 10, 12, 18, 19, 25, 33, 43, 98, 135, 150, 173, 183, 186 Receptors, Serotonin, 183, 186 Recombinant, 22, 183, 194 Recombination, 11, 183 Rectum, 136, 145, 156, 162, 163, 180, 183 Recurrence, 102, 144, 183 Reductase, 166, 168, 183, 187 Refer, 1, 145, 155, 166, 172, 183, 192 Reflux, 97, 183 Regimen, 29, 151, 183 Relaxant, 183 Remission, 183 Renal cell carcinoma, 80, 183 Renal failure, 17, 183 Renal pelvis, 165, 183

Resection, 50, 184 Respiration, 92, 100, 141, 147, 169, 184 Respiratory Burst, 91, 184 Respiratory Paralysis, 131, 184 Retina, 146, 173, 184, 185 Retinal, 22, 52, 89, 173, 184, 185 Retinal Ganglion Cells, 22, 173, 184 Retinoids, 66, 184 Retinol, 184, 185 Retrograde, 22, 23, 184 Retrograde Amnesia, 23, 184 Retrospective, 48, 184 Retrovirus, 98, 184 Rhabdomyolysis, 35, 61, 184 Rheumatoid, 40, 143, 185 Rheumatoid arthritis, 40, 143, 185 Rhodopsin, 173, 184, 185 Ribosome, 185, 192 Rigidity, 175, 177, 185 Risk factor, 4, 5, 180, 185 Risk patient, 20, 185 Rods, 184, 185, 195 S Salicylic, 96, 185 Saline, 90, 91, 185 Saponins, 185, 188 Schizoid, 185, 196 Schizophrenia, 185, 196 Schizotypal Personality Disorder, 185, 196 Sciatic Nerve, 22, 176, 185, 191 Scleroderma, 51, 95, 185 Sclerosis, 170, 185 Scopolamine, 13, 185 Screening, 4, 5, 15, 20, 93, 144, 186 Sebum, 131, 186 Secretion, 7, 8, 9, 10, 62, 95, 131, 144, 147, 160, 168, 169, 186, 194 Sedatives, Barbiturate, 186 Sedimentation, 186, 193 Segregation, 12, 92, 100, 144, 183, 186 Seminiferous tubule, 186, 188 Semisynthetic, 141, 144, 154, 186 Senile, 174, 186 Sensitization, 13, 186 Sepsis, 95, 186 Serotonin, 12, 16, 172, 183, 186, 193 Serrated, 33, 186 Serum, 3, 4, 20, 32, 37, 62, 72, 134, 145, 157, 166, 169, 186, 189, 193 Shock, 94, 134, 186, 192 Side effect, 6, 88, 109, 132, 139, 148, 161, 186, 189, 192

208

Colchicine

Signal Transduction, 15, 24, 37, 186 Simvastatin, 34, 187 Skeletal, 90, 134, 147, 170, 184, 187 Skeleton, 90, 180, 187 Skull, 187, 191 Small intestine, 143, 151, 160, 164, 187 Smooth muscle, 41, 133, 134, 160, 170, 187, 189 Sneezing, 176, 187 Sodium, 77, 90, 158, 169, 187 Soft tissue, 3, 140, 144, 187 Solid tumor, 150, 187 Solvent, 153, 157, 187 Somatic, 152, 167, 169, 175, 187 Somatic cells, 167, 169, 187 Spasmodic, 176, 187 Spastic, 98, 164, 187 Spasticity, 187 Specialist, 121, 188 Specificity, 23, 132, 188 Sperm, 21, 134, 144, 178, 186, 188, 193 Sperm Head, 21, 188 Spermatogenesis, 64, 188 Spermatozoa, 65, 188 Spinal cord, 22, 137, 140, 142, 144, 151, 156, 167, 171, 174, 175, 184, 185, 188 Spinal Cord Diseases, 174, 184, 188 Spinal Nerves, 175, 188 Spinous, 153, 165, 188 Spleen, 134, 166, 188 Splenomegaly, 4, 188 Spondylitis, 60, 188 Sporadic, 13, 171, 188 Squamous, 80, 188 Stabilization, 19, 188 Steatosis, 5, 188 Stellate, 15, 188 Sterile, 94, 174, 188 Sterility, 64, 148, 162, 188 Steroid, 5, 138, 147, 185, 187, 188, 189 Steroid therapy, 5, 189 Stimulant, 160, 189, 194 Stimulus, 151, 163, 164, 189, 191 Stomach, 131, 153, 156, 160, 170, 176, 183, 187, 188, 189 Stool, 145, 162, 164, 189 Stress, 13, 20, 137, 147, 164, 170, 185, 189, 194 Stroke, 7, 114, 189 Structure-Activity Relationship, 80, 189 Stupor, 165, 170, 189 Subacute, 162, 189

Subclinical, 4, 5, 61, 162, 189 Subcutaneous, 4, 151, 175, 189 Subiculum, 160, 189 Subspecies, 188, 189 Substance P, 153, 168, 186, 189 Substrate, 14, 96, 189 Sulfinpyrazone, 4, 189 Superoxide, 21, 91, 184, 189 Superoxide Dismutase, 21, 91, 189 Supportive care, 5, 189 Suppression, 51, 64, 102, 147, 190 Suppressive, 72, 190 Suprachiasmatic Nucleus, 16, 190 Sympathomimetic, 150, 153, 172, 190 Symptomatic, 5, 54, 65, 190 Synapse, 11, 12, 132, 179, 190, 192 Synapsis, 11, 190 Synaptic, 18, 172, 187, 190 Synaptophysin, 12, 16, 190 Systemic lupus erythematosus, 143, 190 Systemic therapy, 143, 190 Systolic, 161, 190 T Telangiectasia, 4, 190 Telencephalon, 19, 138, 180, 190 Telomere, 11, 72, 78, 190 Telophase, 168, 190 Temporal, 16, 19, 21, 23, 160, 191 Temporal Lobe, 23, 191 Tendon, 156, 187, 191 Terminalis, 190, 191 Testis, 21, 153, 191 Tetany, 174, 191 Thalidomide, 53, 64, 191 Therapeutics, 47, 54, 65, 67, 110, 191 Thoracic, 138, 140, 166, 191 Threshold, 17, 161, 191 Thrombin, 155, 181, 191 Thrombocytopenia, 177, 191 Thrombomodulin, 181, 191 Thrombosis, 60, 181, 189, 191 Thyroid, 174, 191, 193 Thyroid Gland, 174, 191 Tibial Nerve, 185, 191 Tomography, 22, 191 Topical, 27, 66, 89, 153, 160, 192 Toxic, iv, 13, 16, 66, 88, 89, 96, 99, 137, 147, 148, 161, 171, 172, 178, 192 Toxicity, 14, 15, 32, 40, 43, 44, 46, 56, 60, 61, 67, 76, 88, 89, 90, 94, 95, 136, 151, 192 Toxicokinetics, 192

209

Toxicology, 13, 16, 30, 31, 35, 42, 44, 52, 66, 78, 116, 192 Toxin, 13, 37, 152, 192 Transcriptase, 98, 184, 192 Transcription Factors, 24, 192 Transduction, 186, 192 Transfection, 139, 192 Transfusion, 159, 192 Translation, 14, 153, 192 Translational, 14, 192 Translocation, 144, 153, 192 Transmitter, 131, 137, 150, 164, 167, 172, 192 Transplantation, 5, 30, 33, 38, 44, 46, 54, 59, 60, 61, 102, 144, 161, 166, 192 Trauma, 171, 192, 196 Treatment Outcome, 50, 192 Tremor, 175, 192 Tricyclic, 98, 193 Trifluralin, 94, 193 Trisomy, 134, 193 Trophic, 86, 193 Tryptophan, 145, 186, 193 Tuberculosis, 14, 136, 185, 193 Tubulin, 10, 13, 14, 24, 26, 27, 45, 47, 52, 55, 57, 63, 75, 77, 78, 80, 85, 88, 92, 99, 100, 168, 193 Tumor marker, 139, 193 Tumor Necrosis Factor, 15, 62, 191, 193 Tumour, 156, 193 Tunicamycin, 62, 193 Tyrosine, 7, 19, 150, 193 U Ulcer, 158, 193, 194 Unconscious, 134, 193 Univalent, 160, 174, 193 Untranslated Regions, 14, 193 Uremia, 183, 193 Ureters, 165, 193 Urethra, 180, 193, 194 Uric, 3, 133, 158, 161, 194 Uricosuric, 83, 189, 194 Urinary, 41, 141, 157, 162, 178, 186, 194, 196 Urine, 37, 135, 140, 145, 147, 150, 162, 165, 171, 178, 181, 183, 193, 194 Urogenital, 157, 194 Ursodeoxycholic Acid, 39, 54, 65, 102, 103, 194 Urticaria, 36, 134, 194 Uterus, 143, 168, 179, 194

V Vaccine, 133, 181, 194 Vacuoles, 174, 194 Vagina, 168, 194 Vaginal, 10, 194 Valine, 175, 194 Varicose, 165, 194 Varicose Ulcer, 165, 194 Vascular, 7, 41, 76, 134, 144, 158, 162, 166, 168, 177, 188, 191, 194 Vasoactive, 16, 194 Vasoconstriction, 153, 194 Vasodilator, 150, 160, 194 Vector, 22, 192, 194 Vein, 164, 172, 175, 178, 194 Venous, 4, 140, 165, 181, 194 Ventricle, 160, 161, 182, 190, 194 Venules, 140, 141, 168, 195 Verapamil, 39, 81, 195 Vertebrae, 188, 195 Veterinary Medicine, 115, 195 Vibrio, 143, 195 Vibrio cholerae, 143, 195 Vinblastine, 26, 39, 41, 47, 69, 79, 80, 99, 193, 195 Vinca Alkaloids, 23, 40, 47, 195 Vincristine, 193, 195 Viral, 21, 98, 173, 184, 192, 195 Viral vector, 21, 195 Virulence, 192, 195 Virus, 21, 26, 28, 98, 157, 159, 163, 177, 192, 195 Visceral, 137, 172, 176, 195 Vitro, 15, 35, 195 Vivo, 91, 166, 195 Vomeronasal Organ, 173, 195 W White blood cell, 135, 138, 158, 166, 167, 169, 172, 177, 195 Whooping Cough, 176, 195 Withdrawal, 5, 196 Wound Healing, 35, 36, 196 Wound Infection, 95, 196 X Xanthine, 133, 196 Xanthine Oxidase, 133, 196 Xenograft, 134, 196 X-ray, 37, 48, 155, 164, 172, 182, 183, 196 X-ray therapy, 164, 196 Y Yeasts, 176, 196

210

Z

Colchicine

Zymogen, 181, 196

211

212

Colchicine