TETRACYCLINE 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., 1960Tetracycline: A Medical Dictionary, Bibliography, and Annotated Research Guide to Internet References / James N. Parker and Philip M. Parker, editors p. cm. Includes bibliographical references, glossary, and index. ISBN: 0-597-84651-0 1. Tetracycline-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.
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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 tetracycline. 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 TETRACYCLINE ......................................................................................... 3 Overview........................................................................................................................................ 3 The Combined Health Information Database................................................................................. 3 Federally Funded Research on Tetracycline................................................................................... 5 E-Journals: PubMed Central ....................................................................................................... 64 The National Library of Medicine: PubMed ................................................................................ 86 CHAPTER 2. NUTRITION AND TETRACYCLINE.............................................................................. 133 Overview.................................................................................................................................... 133 Finding Nutrition Studies on Tetracycline ............................................................................... 133 Federal Resources on Nutrition ................................................................................................. 137 Additional Web Resources ......................................................................................................... 138 CHAPTER 3. ALTERNATIVE MEDICINE AND TETRACYCLINE ....................................................... 143 Overview.................................................................................................................................... 143 National Center for Complementary and Alternative Medicine................................................ 143 Additional Web Resources ......................................................................................................... 157 General References ..................................................................................................................... 160 CHAPTER 4. DISSERTATIONS ON TETRACYCLINE ......................................................................... 161 Overview.................................................................................................................................... 161 Dissertations on Tetracycline .................................................................................................... 161 Keeping Current ........................................................................................................................ 162 CHAPTER 5. PATENTS ON TETRACYCLINE .................................................................................... 163 Overview.................................................................................................................................... 163 Patents on Tetracycline.............................................................................................................. 163 Patent Applications on Tetracycline.......................................................................................... 190 Keeping Current ........................................................................................................................ 222 CHAPTER 6. BOOKS ON TETRACYCLINE ........................................................................................ 223 Overview.................................................................................................................................... 223 Book Summaries: Online Booksellers......................................................................................... 223 Chapters on Tetracycline ........................................................................................................... 224 CHAPTER 7. PERIODICALS AND NEWS ON TETRACYCLINE .......................................................... 229 Overview.................................................................................................................................... 229 News Services and Press Releases.............................................................................................. 229 Newsletter Articles .................................................................................................................... 231 Academic Periodicals covering Tetracycline .............................................................................. 232 CHAPTER 8. RESEARCHING MEDICATIONS .................................................................................. 233 Overview.................................................................................................................................... 233 U.S. Pharmacopeia..................................................................................................................... 233 Commercial Databases ............................................................................................................... 234 APPENDIX A. PHYSICIAN RESOURCES .......................................................................................... 239 Overview.................................................................................................................................... 239 NIH Guidelines.......................................................................................................................... 239 NIH Databases........................................................................................................................... 241 Other Commercial Databases..................................................................................................... 243 APPENDIX B. PATIENT RESOURCES ............................................................................................... 245 Overview.................................................................................................................................... 245 Patient Guideline Sources.......................................................................................................... 245 Finding Associations.................................................................................................................. 256 APPENDIX C. FINDING MEDICAL LIBRARIES ................................................................................ 259 Overview.................................................................................................................................... 259 Preparation................................................................................................................................. 259
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Finding a Local Medical Library................................................................................................ 259 Medical Libraries in the U.S. and Canada ................................................................................. 259 ONLINE GLOSSARIES................................................................................................................ 265 Online Dictionary Directories ................................................................................................... 265 TETRACYCLINE DICTIONARY................................................................................................ 267 INDEX .............................................................................................................................................. 377
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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 tetracycline 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 tetracycline, 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 tetracycline, 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 tetracycline. 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 tetracycline, 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 tetracycline. 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 TETRACYCLINE Overview In this chapter, we will show you how to locate peer-reviewed references and studies on tetracycline.
The Combined Health Information Database The Combined Health Information Database summarizes studies across numerous federal agencies. To limit your investigation to research studies and tetracycline, 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 “tetracycline” (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: •
Ranitidine Bismuth Citrate, Tetracycline, Clarithromycin Twice-A-Day Triple Therapy for Clarithromycin Susceptible Helicobacter Pylori Infection Source: Alimentary Pharmacology and Therapeutics. 13(2): 169-172. February 1999. Contact: Available from Alimentary Pharmacology and Therapeutics. Blackwell Science Ltd., Osney Mead, Oxford OX2 OEL, UK. +44(0)1865 206206. Fax +44(0)1865 721205. Email:
[email protected]. Website: www.blackwell-science.com. Summary: Although many combination therapies have been proposed, there is still interest in identifying simple, inexpensive, effective protocols that have high rates of success. This article reports on a study undertaken to investigate the role of the new soluble form of bismuth (ranitidine bismuth citrate) in twice a day therapy for Helicobacter pylori infection. Patients with histologically and culture proven H. pylori
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infection received ranitidine bismuth citrate 400 mg, tetracycline HCl 500 mg, and clarithromycin 500 mg, each b.d. for 14 days, followed by 300 mg ranitidine once a day for 4 additional weeks. Outcome was assessed 4 or more weeks after the end of antimicrobial therapy by repeat endoscopy with histology and culture (49 patients) or urea breath testing (14 patients). Sixty three patients completed the therapy (59 men and 4 women; average age 56.7 years, range 31 to 75 years). All patients had clarithromycin susceptible strains prior to therapy. H. pylori infection was cured in 94 percent. There was a therapy failure in one patient who took the medicine for only 1 day and stopped because of side effects. Three of the isolates from treatment failures were available post failure; two were clarithromycin resistant and one was susceptible. Side effects, primarily diarrhea, were severe in two patients (3 percent) and moderate in three. The authors conclude that this therapeutic regimen was well tolerated and effective for the treatment of H. pylori infection in patients with clarithromycin susceptible H. pylori. 33 references. (AA-M). •
Controlled Local Delivery of Tetracycline with Polymer Strips in the Treatment of Periodontitis Source: Journal of Periodontology. 73(1): 13-19. January 2002. Contact: Available from American Academy of Periodontology. Suite 800, 737 North Michigan Avenue, Chicago, IL 60611-2690. (312) 573-3220. Fax (312) 573-3225. Summary: Several antibacterial agents have been studied as a means to produce bactericidal or bacteriostatic activity as an adjunct to the mechanical treatment of periodontal disease. This article reports on a study undertaken to evaluated the efficacy of tetracycline strips administered singly or in multiples in conjunction with root planning, versus root planning alone, or to an untreated control. Secondary purposes were to compare gingival crevicular fluid (GCF) volume and GCF concentrations of tetracycline in pockets treated with strips; to evaluate strip insertion time; and to compare ease of placement for single or multiple strips. Using a 4 quadrant design, 4 test teeth in 24 patients were treated with either root planning and single strip application; root planning and multiple strip application; root planning alone; or an untreated control. Single and multiple strip placement resulted in a significant reduction in probing depth compared to root planning and untreated groups. The multiple strip group significantly decreased bleeding on probing compared to all other treatment groups. There was no treatment effect on GCF; however, there was a significant reduction in the GCF volume over time. The time required for placement was, on average, 1.9 minutes for single strips and 3.25 minutes for multiple strips. The authors conclude that multiple strips are superior to a single strip in reducing bleeding on probing, and that local delivery of tetracycline is superior to root planning alone in reducing probing depth. 1 figure. 4 tables. 23 references.
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Tetracycline-Loaded Fibers as Adjunctive Treatment in Periodontal Disease Source: JADA. Journal of the American Dental Association. 125(9): 1199-1230. September 1994. Summary: This article reports on a study in which fiber placed in periodontal pockets to deliver tetracycline continuously for 10 days was effective in reducing pocket depth and bleeding on probing when used as an adjunct to scaling and root planing. Sixty-six adults, aged 21 years and older, participated in this open-label study. Each had one or more periodontal pockets of at least 4 mm that bled on probing and each had received active (non-surgical or surgical) periodontal treatment. The author describes the
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application of the fiber; efficacy and safety observations; and results, including reduction in pocket depth, bleeding on probing, adverse effects, and fiber placement and retention. The author concludes that tetracycline fiber used with scaling and root planing was clearly effective in reducing the clinical signs of inflammatory adult periodontitis. 3 tables. 21 references. (AA-M). •
Do Minocycline and Other Tetracyclines Have a Place in Rheumatology? Source: Revue du Rhumatisme (English ed.). 64(7-9): 474-480. July-September 1997. Summary: This journal article provides health professionals with information on the potential usefulness of antimicrobials such as tetracycline for the treatment of rheumatoid arthritis. Tetracyclines are a family of antimicrobials with activity against a broad range of organisms, including those that develop intracellularly. Links have been reported between some infections and some inflammatory joint diseases, with the most notable example involving mycoplasmas and rheumatoid arthritis. Reactive arthritides are known to be triggered by organisms found in the gastrointestinal or genitourinary tract, and antigenic material from these organisms has recently been demonstrated in synovial tissue from patients with reactive arthritis. These factors led to the hypothesis that tetracyclines may be useful in rheumatoid arthritis and reactive arthritis. Two controlled studies found that minocycline benefited patients with rheumatoid arthritis when it was given either as an adjunct to another second line treatment or as the only slow acting drug. Lymecycline has been found to expedite recovery from reactive arthritis due to Chlamydia trachomatis, and tetracycline to decrease the incidence of reactive arthritis due to sexually transmitted diseases. The safety profiles of these treatments were acceptable in all available studies but require further investigation for long term administration. The benefits may be related to the immunomodulating effects of tetracyclines or their ability to inhibit metalloproteases such as collagenases. Whether tetracycline therapy influences the course of radiologic lesions in rheumatoid arthritis remains unknown. However, minocycline therapy has given sufficient proof of its efficacy to make it an attractive alternative in rheumatoid arthritis. No data are available on the usefulness of tetracycline therapy in human osteoarthritis. 2 tables and 42 references. (AA-M).
Federally Funded Research on Tetracycline The U.S. Government supports a variety of research studies relating to tetracycline. 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 tetracycline.
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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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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 tetracycline. The following is typical of the type of information found when searching the CRISP database for tetracycline: •
Project Title: A NOVEL GROWTH REGULATORY FACTOR IN BREAST CELLS Principal Investigator & Institution: Montano, Monica M.; Pharmacology; Case Western Reserve University 10900 Euclid Ave Cleveland, Oh 44106 Timing: Fiscal Year 2002; Project Start 01-APR-2002; Project End 31-MAR-2007 Summary: (provided by the applicant) The vast majority of human breast cancers are initially hormone-dependent with estradiol playing a crucial role in their development and evolution (1). However there is relatively little known about how estrogen activation of the estrogen receptor (ER) results in the initiation or promotion of human breast cancer. We have identified a novel gene that is down regulated by estradiol, Estrogen-Down-regulated Gene 1 (EDG1), in breast epithelial cells. Subsequent studies indicate that EDG1 inhibits ERalpha transcriptional activity. A self-contained tetracycline-regulated retroviral vector system (2) has been used to both positively and negatively regulate the expression of EDG1 in breast cancer cells (MCF7 and MDA-MB231) and normal breast cells (MCF 10A). Compared to control cells, cells that over express EDG 1 (MCF7-EDG 1, MCF 10-EDG1 and MDA-MB-23 1-EDG1) exhibit decreased growth rate, while cells that have decreased EDG1 expression (MCF7EDG1AS and MCF10-EDG1AS) have enhanced growth rate. Moreover EDG1 overexpression inhibited anchorage independent growth and estrogen-induced MCF7 proliferation. While we see cross talk between estrogen and EDG1, we propose that EDG1 may also function as a tumor suppressor independent of ERa levels. A mechanistic basis for the growth effect of EDG1 is suggested by the interaction of EDG1 with Integrin beta4-interactor protein (p27/BBP) and the 67 kD laminin receptor (67LR). p27/BBP protein interacts with the cytodomain of beta4 integrin and has been proposed to link beta4 integrin with the cytoskeleton, while 67LR binds to laminins and interacts with the alpha6beta4 integrin multimeric complex. Based on our preliminary findings we hypothesize that the growth inhibitory effects of EDG1 in breast cells have ERalphadependent and ERalphs-independent components; and EDG1 helps maintain the balance of signaling events generated through the extracellular matrix that regulates normal breast epithelial cell function. To test our hypothesis we will: (1) characterize EdG1 inhibition of ERalpha transcriptional activity and its role in the growth inhibitory effects of EDG1 (2) examine the role of Integrin-beta4-interactor protein and the 67 kD laminin receptor in EDG1 cellular effects and (3) characterize other phenotypic effects of EDG1 and identification of other downstream effectors of EDG1. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen
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Project Title: ADULT AND DEVELOPMENTAL ROLES OF CAMKII IN LEARNING Principal Investigator & Institution: Griffith, Leslie C.; Associate Professor; Brandeis University 415 South Street Waltham, Ma 024549110 Timing: Fiscal Year 2002; Project Start 10-SEP-2002; Project End 31-JUL-2007 Summary: (provided by applicant): A number of signal transduction pathways have been implicated in behavioral, developmental and synaptic plasticity using pharmacological and genetic manipulations. Molecules identified as important in the generation of both short-term and long-term plasticity include CaMKII and PKA. The overlapping use of a few biochemical pathways to set up the circuitry for, and mediate,
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complex behaviors implies the existence of important temporal and/or spatial constraints on activity. This proposal is will use novel methods in Drosophila to detect and manipulate the spatial and temporal patterns of activation of protein kinases. Specific Aim #1 will probe the role of CaMKII autoregulation and localization in associative memory formation using temporally controlled expression of mutant kinase transgenes in cells known to be part of the memory circuit. Concurrent temporal and spatial control will be achieved by using either selectively inhibitable kinase transgenes or a tetracycline-controlled GAL4 enhancer trap strategy. The role of modulation of excitability as an important downstream consequence of CaMKII activation will be tested by manipulation of Eag potassium channel activity. Specific Aim #2 will identify the developmental window during which CaMKII acts to modify adult circuit formation. Once this window is established we will identify the sensitive cell groups. The morphological and gene expression consequences of early manipulation of CaMKII will be explored. Specific Aim #3 will develop and implement genetically based sensors to measure the activation of kinases in real time in intact behaving animals. The initial sensor will detect kinases such as PKA that activate gene expression via CREB and are also involved in short-term plasticity. These experiments will give us temporal and spatial information about the use of biochemical pathways during development and behavior. The high level of synteny in the biochemistry of neuronal function between mammals and flies leads to the expectation that these studies will have relevance for human learning disabilities. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •
Project Title: AGE RELATED DEGENERATION Principal Investigator & Institution: Epstein, Charles J.; Professor of Pediatrics & Biochemistry; Pediatrics; University of California San Francisco 500 Parnassus Ave San Francisco, Ca 941222747 Timing: Fiscal Year 2002; Project Start 20-SEP-1998; Project End 31-JUL-2004 Summary: The objective of this project is to determine the effects of alterations in the balance of oxygen free radical metabolizing enzymes on the aging process. There is considerable interest in the role which oxygen free radicals may play in the aging process, as well as in the genesis of many types of degenerative processes and reactions to trauma. A powerful approach to the investigation of these issues is to perturb the system for handling oxygen free radicals, and many ways of doing so have been used. Genetically modified animals have been used for this purpose and have been found to be a particularly powerful method for producing the types of perturbations desired, because of both the reproducibility of the changes produced and their stability over time. In this proposal are described a series of studies of the effects of altered CuZnsuperoxide dismutase (CuZnSOD) and/or MnSOD activities on age-related and induced degenerative changes in the brain, heart, and other organs, on the accumulation of mitochondrial and nuclear DNA mutations and of other biomarkers of oxidative stress, and on various aspects of mitochondrial function. Particular attention will be paid to the effects of free radical imbalance on the central nervous system, and agedependent changes in learning and memory and in the function of the basal forebrain cholinergic system will be assessed. The animals to be studied will include transgenic mice overexpressing either CuZnSOD or MnSOD, mutant mice completely lacking in CuZnSOD, and mice with absent or very low levels of MnSOD. To engineer the mice with low levels of MnSOD activity, the tetracycline-regulated transgenic transactivator system will be used and will be adapted to produce low expression of the gene for MnSOD. The strains of genetically altered mice which will be generated in this project,
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along with those which already exist, constitute a unique set of model animals which will make it possible to study the effects on age-related degenerative processes of intracellular SOD activities ranging from absent to greatly elevated and of the resulting alterations of superoxide levels. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •
Project Title: ALS, SOD AND PEROXYNITRITE Principal Investigator & Institution: Beckman, Joseph S.; Professor & Director; None; Oregon State University Corvallis, or 973391086 Timing: Fiscal Year 2002; Project Start 01-AUG-1994; Project End 31-JUL-2004 Summary: Over 60 different dominant missense mutations to the Cu, Zn superoxide dismutase gene are associated with motor neuron death in amyotrophic lateral sclerosis (ALS). The apparent gain-of-function conferred by these SOD mutations remains elusive. Four broad theories have been proposed to account for the gain-of-function: an amyloid effect due to aberrant protein folding unrelated to free radicals; toxicity due to reactions of SOD with hydrogen peroxide; the loss of zinc leading to altered redox reactions by SOD; and increased tyrosine nitration. Our preliminary data suggests that zinc-deficient SOD causes increased tyrosine nitration and apoptosis in motor neurons. In the present application, we propose to test these four general theories utilizing new lines of ALS- SOD transgenic mice where mutant ALS SOD expression is controlled by a tetracycline- inducible promoter. The inducible expression will allow us to determine how long expression of mutant SOD is necessary to induce motor neuron death and whether down regulating expression of ALS SOD allows motor neurons to be rescued. Other transgenic lines expressing ALS-SODs with additional mutations to eliminate zinc and copper binding will be made to determine the roles of these metals in the development of motor neuron disease. We have developed novel assays to measure formation of hydrogen peroxide, accumulation of zinc-deficient SOD and tyrosine nitration in vivo, which will be used to determine whether expression of these mutant SODs affects these factors as mice develop disease. From in vitro expression experiments, we have discovered that one cysteine residue renders the ALS-SOD mutant proteins vulnerable to aggregation. We will determine whether mutation of this cysteine residue increases or decreases the toxicity of ALS-SODs in transgenic mice and how it affects intracellular aggregation. These experiments will critically test the contributions of protein aggregation, metal ions and oxidative stress in SOD-induced degeneration of motor neurons in vivo. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen
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Project Title: ANALYSIS OF T CELL PHENOTYPE AND FUNCTION IN SCURFY MICE Principal Investigator & Institution: Kasprowicz, Deborah J.; Benaroya Research Inst at Virginia Mason 1201 9Th Ave Seattle, Wa 98101 Timing: Fiscal Year 2003; Project Start 12-MAY-2003; Project End 31-MAY-2004 Summary: (provided by the applicant): In X-linked scurfy (sf') disease, male mice develop severe autoimmune lymphoproliferative disease that is fatal within twenty-one days of age The pathology of this disease results from chronically activated CD4 v T cells that over-produce a wide variety of cytokines However, the mechanism by which T cells are initially activated is yet unknown FoxP3, the gene mutated in scurfy disease, has been cloned and is a member of the forkhead/ winged helix domain family When wild-type FoxP3/scurfin is over-expressed in otherwise normal mice, the mice are
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immunocompromised The human homolog of FoxP3 has been cloned and is mutated in IPEX syndrome Males afflicted with IPEX develop multiple autoimmune diseases including IDDM and do not survive beyond a year of age Taken together, these findings are consistent with scurfin having a role as a regulatory protein in T cell activation One model suggests that the level of scurfin expression in T cells determines the threshold of TCR stimulation required for T cell activation The absence of scurfin generates T cells that are hyper-responsive to TCR stimulation and lowers the threshold of tolerance to self-Ags Over-expression of scurfin increases the threshold of TCR sensitivity such that T cells are non-responsive to TCR stimulation The experiments in this proposal are designed to test this model In Specific Aim 1, we will determine the effect of the level and timing of scurfin expression on the development of tolerance or disease in A) sfmutant/GAD65 TCR Tg mice or B) FoxP3 Tg/NOD mice In Specific Aim 2, we will determine the regions in the FoxP3 gene plomoter that are responsible for regulating scurfin expression during the transition of T cells from naive to effector cells This work will provide valuable insight into the regulatory pathway(s) that fail allowing for the development of autoimmune disease. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •
Project Title: ANTIBIOTIC HYPERSUSCEPTIBILITY MUTATIONS IN BACTERIA Principal Investigator & Institution: Neyfakh, Alex A.; Associate Professor; Medicinal Chem & Pharmacognosy; University of Illinois at Chicago 1737 West Polk Street Chicago, Il 60612 Timing: Fiscal Year 2002; Project Start 15-FEB-2002; Project End 31-JAN-2006 Summary: (Adapted from the Applicant's Abstract): The escalating problem of bacterial resistance to antibiotics calls for radical changes in the existing antibacterial therapies. One of the most promising approaches is the use of antibiotic potentiators, compounds that make bacterial cells hypersusceptible to antibiotics. The goal of the project is to identify multiple novel molecular targets for potentiators. This will be accomplished by isolating antibiotic hypersusceptibility mutations of Gram-negative bacteria, Acinetobacter and/or Escherichia coli. These mutations will specify bacterial proteins whose inhibition is likely to potentiate antimicrobial action of antibiotics. Antibiotic hypersusceptibility is a very difficult phenotype to select, and only few such mutations are known. We have designed and tested a novel genetic strategy for selection of hypersusceptibility mutations, termed SDR. Application of this strategy will identify multiple mutations increasing bacterial susceptibility to beta-lactams (ampicillin, ceftazidime, imipenem), translational inhibitors (erythromycin, linezolid, tetracycline, and chloramphenicol) and fluoroquinolone antibiotics (ciprofloxacin). The molecular mechanisms underlying the effects of the most interesting of these mutations will be analyzed. In addition to identifying promising targets for potentiators, the project will help unravel new aspects of the mechanism of action of antibiotics and new features of bacterial physiology. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen
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Project Title: ASPL TFE3 FUSION IN HUMAN CANCERS Principal Investigator & Institution: Ladanyi, Marc; Sloan-Kettering Institute for Cancer Res New York, Ny 10021 Timing: Fiscal Year 2002; Project Start 01-APR-2002; Project End 31-MAR-2007 Summary: (provided by applicant) The novel ASPL-TFE3 fusion arises from a t(X;17)(q25.3;p11.2) in two distinct human cancers, alveolar soft part sarcoma (ASPS), a
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lethal sarcoma of uncertain lineage, and a unique subset of pediatric renal adenocarcinomas. In these two tumor types, the gene fusions occur respectively through an unbalanced or balanced t(X;17). ASPL is a novel ubiquitously expressed gene that encodes a protein with no recognizable complex motifs, but is similar to unknown predicted proteins in several model organisms. The ASPL-TFE3 fusion replaces the Nterminal portion of TFE3 by the fused ASPL sequences, while retaining the DNAbinding domain of the TFE3 transcription factor, implicating transcriptional deregulation in the pathogenesis of this tumor. Preliminary transactivation and subcellular localization data support the function of ASPL-TFE3 as a transcription factor. ASPL-TFE3 is of special interest as the only chimeric transcription factor associated with malignancies of both mesenchymal and epithelial derivation. The overall goal of this proposal is to extend the understanding of the biology of these genes and tumors through functional studies, gene expression profiling, and molecular genetic analyses. In Aim 1, the investigators will map the putative ASPL activation domain and perform a transactivation analysis of the reciprocal TFE3-ASPL product; examine transactivation of reporters driven by portions of endogenous TFE3 target promoters where cooperative interactions with other transcription factors are critical; and analyze specific ASPL-TFE3 protein-protein interactions. In Aim 2, they will use microarray hybridizations to examine genes induced by TFE3 and ASPL-TFE3 in heterologous human mesenchymal and renal cell lines stably transfected with tetracycline-regulated TFE3 and ASPL-TFE3 constructs, and to establish and compare expression profiles of ASPS and pediatric renal adenocarcinomas containing ASPL-TFE3, and other major types of renal adenocarcinomas. Finally, in Aim 3, to address the hypothesis that the unbalanced structure of the t(X;17) in ASPS is driven by a growth advantage conferred to ASPS cells by the functional loss of a gene on 17q25.3 telomeric to ASFL, the investigators will examine polymorphic loci in Xp11.2->qter in ASPS from women to establish whether the t(X;17) of ASPS forms only in G2 or shows no intrinsic cell cycle preference; close sequence gaps in the ASFL-containing BAC and orient and order the sequence fragments, to determine which genes are telomeric to ASPL; analyze exceptional ASPS cases with a reciprocal t(X;17) for smaller deletions of 17q25.3->qter; and finally analyze selected candidate genes in the same region for inactivating mutations. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •
Project Title: AZITHROMYCIN COMBINATION THERAPY IN RESISTANT MALARIA Principal Investigator & Institution: Knirsch, Charles; Charles Knirsch, Md, Mph 235 E 42Nd St New York, Ny 10017 Timing: Fiscal Year 2000; Project Start 30-SEP-2000; Project End 31-MAR-2005 Summary: The emergence of in vivo resistance of Plasmodium falciparum malaria to standard antimalarial drugs is a major and growing threat to public health in Africa, Asia, and Latin America. Chloroquine treatment is now rarely effective. The usual replacement, Fansidar, is already losing efficacy. Compliance with quinine can only be achieved for 3 days because of intolerance, and 3 days does not result in cure. Artesunate, also usually given for 3 days, is again not curative. Pregnant women and young children bear the brunt of this disease, and constitute a particularly difficult treatment problem because the drugs commonly added to the above standard agents to augment efficacy-such as doxycycline/tetracycline or mefloquine-are contraindicated for these populations. Azithromycin is an agent that can be safely administered to all the above clinical populations, and the single-agent efficacy of azithromycin in the clinic is comparable to that of doxycycline /tetracycline.The overall aims of this project are to
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determine if combinations of azithromycin with the above standard agents provide satisfactory efficacy and tolerance including in pregnant women and children and if so, to formally develop such combinations for use in the US and worldwide. B. Specific Milestones and their associated hypotheses MILESTONE 1: test the hypothesis that in phase II "proof of concept"/dose-ranging clinical trials, One or more of the combinations of azithromycin with quinine, fansidar, chloroquine, or artesunate will be effective (90% cure) and well-tolerated for the treatment of uncomplicated P falciparum disease in relatively non-immune populations and also in semi-immune pregnant women. MILESTONE 2: test the hypothesis that in phase II/III clinical trials, the efficacious azithromycin combinations identified in milestone 1 are as safe and well tolerated. MILESTONE 3: test the hypothesis that in phase III pivotal trials including pregnant women and children, the efficacious azithromycin combinations identified in milestones 1 and 2 are safe and effective (95% cure) for drug-resistant malaria. MILESTONE 4: file a supplemental New Drug Application to the United States Food and Drug Administration for the use of azithromycin drug combinations for the treatment of P falciparum malaria, including in pregnant women and children. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •
Project Title: BACTERIAL AROMATIC POLYKETIDE SYNTHASES Principal Investigator & Institution: Khosla, Chaitan S.; Professor; Chemical Engineering; Stanford University Stanford, Ca 94305 Timing: Fiscal Year 2002; Project Start 20-AUG-1998; Project End 31-MAR-2007 Summary: (provided by applicant) Polyketide synthases (PKSs) are a family of multienzyme assemblies that catalyze the biosynthesis of numerous structurally complex and biologically important natural products. Bacterial aromatic PKSs are one subclass of PKSs responsible for the biosynthesis of natural products such as doxorubicin and tetracycline. They are composed of 3-10 distinct subunits, which together synthesize a polyfunctional aromatic product. The modularity of these multi-enzyme systems has been exploited via genetic engineering for the biosynthesis of numerous "unnatural" natural products. However, our understanding of the structural and mechanistic principles by which these remarkable enzymes assemble and catalyze multi-step transformations involving highly reactive intermediates is rudimentary. During the past proposal period we have expressed, purified, and reconstituted the actinorhodin (act), tetracenomycin (tcm), and parts of the R1128 PKSs. This has allowed us to probe the properties of selected aromatic PKS components using a combination of mutagenesis, protein chemical, structural (NMR and X-ray crystallography), and biosynthetic engineering approaches. The specific goals for the next proposal period are: 1) Development of improved expression systems, purification procedures, and assay systems for aromatic PKSs and their components, 2) Further structural and mechanistic analysis, and biosynthetic exploitation of the unusual primer unit tolerance of the R1128 PKS, 3) Further structural and mechanistic analysis, and engineering of the chain length specificity of the act, tcm, and possibly other minimal PKSs, 4) Dissecting and engineering the malonyl-CoA selectivity of the malonyl-CoA:acyl carrier protein acyltransferase, 5) Analyzing the kinetic consequences of protein-protein interactions between the ketosynthase, acyl carrier protein, and acyltransferase, and 6) Engineering a hybrid PKS that contains components of an aromatic and a modular PKS. These studies, which follow logically from our results thus far, are expected to provide interesting and important insights into structure-function relationships within this remarkable family of multi-enzyme assemblies. Furthermore, knowledge acquired in the process could
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expand the utility of bacterial aromatic PKSs (and possibly other PKSs as well) for the engineered biosynthesis of novel natural products. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •
Project Title: BIOENERGETICS IN ANIMAL MODELS OF HUNTINGTON'S DISEASE Principal Investigator & Institution: Beal, M Flint.; Professor; Neurology and Neuroscience; Weill Medical College of Cornell Univ New York, Ny 10021 Timing: Fiscal Year 2003; Project Start 15-APR-1999; Project End 31-MAR-2008 Summary: (provided by applicant): The pathogenesis of Huntington's Disease (HD) is as yet unknown but there is substantial evidence that both altered gene transcription as well as mitochondrial dysfunction play an important role. There is evidence that huntingtin binds to transcription factors which results in decreased expression of genes which may play a critical role in neuronal survival. A secondary consequence of this appears to be impaired oxidative phosphorylation and increased generation of reactive oxygen species. In our prior grant, we showed that there was impaired oxidative phosphorylation in transgenic mouse models of Huntington's disease, and that this was associated with increased oxidative damage. We also showed that agents such as creatine and coenzyme Q, which improve cellular bioenergetics, exert neuroprotective effects in transgenic mouse models of Huntington's disease. In the present proposal, we intend to extend these studies to two further unique transgenic mouse models of Huntington's disease. We will determine whether there is mitochondrial dysfunction and oxidative damage in a knock-in mouse model developed by MacDonald and colleagues. These mice are a very accurate genetic model of Huntington's disease. We will also examine the tetracycline-off model developed by Yamamoto and colleagues to determine whether there is mitochondrial dysfunction and oxidative damage with the gene turned on, which then resolves once the gone is turned off. We will carry out similar studies with an inducible cell culture model. We will investigate whether histone deacetylase (HDAC) inhibitors exert neuroprotective effects by altering gene transcription in transgenic mouse models of Huntington's disease. We will examine whether a phosphodiesterase IV inhibitor can exert neuroprotective effects in transgenic mouse models of HD by increasing cyclic AMP levels, leading to increased CREB transcriptional activity, and whether this improves mitochondrial function. Our prior studies showed that combinations of agents, which target different disease mechanisms in Huntington's disease, may exert additive neuroprotective effects. We will, therefore, examine whether a combination of creatine or coenzyme Q with either a HDAC inhibitor or a phosphodiesterase IV inhibitor can exert additive neuroprotective effects. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen
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Project Title: APOPTOSIS
CASPASE
CLEAVAGE
OF
MEF2
MEDIATES
NEURONAL
Principal Investigator & Institution: Lipton, Stuart A.; Professor and Director; Burnham Institute 10901 N Torrey Pines Rd La Jolla, Ca 920371005 Timing: Fiscal Year 2003; Project Start 01-AUG-2003; Project End 31-JUL-2007 Summary: (provided by applicant): Apoptotic neuronal cell death may play a role in many acute and chronic neurologic disorders. These disorders range from acute stroke, head trauma and epilepsy to more chronic states, such as Huntington's disease, Alzheimer's disease, amyotrophic lateral sclerosis, HIV-associated dementia, and glaucoma. Moreover, a contributing factor to such damage is excessive excitation of
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glutamate receptors, particularly (but not exclusively) the N-methyI-D-aspartate (NMDA) subtype of glutamate receptor because of its high permeability to Ca 2+ and subsequent free radical generation. The aim of this proposed research project is to uncover the role of myocyte enhancer factor-2 (MEF2) transcription factors in this excitotoxic/apoptotic process in neurons during ischemic stroke in vivo. MEF2 transcription factors are activated by p38 mitogen-activated protein kinase during neuronal and myogenic differentiation. Recent work has shown that stimulation of this pathway is anti-apoptotic in stem cells but pro-apoptotic in mature neurons exposed to mild excitotoxic or other stresses. Here, preliminary data in vitro show that mild excitotoxic (NMDA) insults to mature cerebrocortical neurons activate caspases-3, -7, in turn cleaving MEF2A, C and D isoforms. Endogenous MEF2 cleavage fragments containing a truncated transactivation domain but preserved DNA binding domain are shown to block MEF2 transcriptional activity via dominant interference. In vitro transfection of constitutively-active/uncleavable MEF2 (MEF2-CA) rescues MEF2 transcriptional activity following NMDA insult and prevents neuronal apoptosis. Conversely, dominant-interfering MEF2 (MEF2-DN) abrogates neuroprotection by MEF2C-CA. Our underlying hypothesis is that these results obtained in vitro can now be applied in vivo using tetracycline (or doxycycline, "dox")-controlled transgenic mice expressing these MEF2-CA and MEF2-DN transgenes. This grant will define a novel pathway to neuronal apoptosis in ischemia via caspase-catalyzed cleavage of MEF2. The Specific Aims are as follows: 1. To characterize anti-apoptotic effects of MEF2-CA in stroke using dox-controlled transgenic mice. 2. To characterize the effect of caspase cleavage fragments of MEF2 as dominant interfering forms that contribute to stroke damage using dox-controlled transgenic mice that express doxycycline-controlled, MEF2 cleavage products. 3. To characterize MEF2 transcriptional activity in vivo after an hypoxic/ischemic (stroke) insult but prior to cell loss using a MEF2-indicator mouse that has been engineered to activate the LacZ gene in accord with the degree of MEF2 transcriptional activity (designated des-mef2-LacZ). Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •
Project Title: CHEMOKINE THERAPEUTIC TARGETS FOR KIDNEY DISEASE Principal Investigator & Institution: Kelley, Vicki R.; Associate Professor of Medicine; Brigham and Women's Hospital 75 Francis Street Boston, Ma 02115 Timing: Fiscal Year 2002; Project Start 01-FEB-2001; Project End 31-JAN-2005 Summary: n influx of leukocytes is common to progressive kidney diseases. Targeting specific molecules responsible for recruitment of leukocytes into the kidney provides a therapeutic strategy for halting tissue progressive damage. Monocyte chemoattractant protein-1(MCP-1) belongs to a family of "chemokines" which attract leukocytes to tissues targeted for inflammation. MCP-l is abundantly expressed by renal parenchymal cells during progressive renal injury. Blockade of MCP-l reduces the influx of activated macrophages, thereby sparing the tubules from macrophage mediated apoptotic destruction in acute nephrotoxic serum nephritis. The MRL-Faslpr model is appealing to identify therapeutic targets for progressive kidney disease since renal destruction is spontaneous, steadily progressive, predictable, fatal and shares features with human illnesses. Kidney disease in the MRL-Faslpr model is complex and consists of glomerular, tubular and peri-vascular damage, accompanied by an robust influx of macrophages and lymphocytes. MCP-1 is vigorously expressed in the MRL-Faslpr kidney prior to injury, and increases with advancing disease. We have constructed an MRL-Faslpr strain genetically deficient in MCP-1 and determined that mice lacking MCP-l live far longer than the wild-type strain. Using genetic approaches, we propose to
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test the hypothesis that MCP-1 is a therapeutic target for progressive autoimmune kidney disease. We propose to: 1) determine whether MCP-1 is required for autoimmune renal disease. We will establish whether MCP-1(-/-) deficient MRL-Faslpr mice are protected from kidney disease, and determine whether protection is exclusive to the kidney, or is systemic. 2) determine whether delivery of MCP-1 into the kidney amplifies or incites progressive renal disease. Using a retroviral gene transfer approach that provides for sustained delivery of MCP-l to a discrete area of the kidney, we propose to determine the impact of local MCP-1 expression on renal pathology, and to investigate whether MCP-1 restores pathology within a discrete area in MCP-l deficient MRL-Faslpr kidneys. We will establish whether MCP-1 is required for autoimmune nephritis in the NZM241O strain. 3) establish whether delivery of MCP-1 receptor antagonist (MCP-1ra) into the MRLFaslpr kidney prevents injury. We propose to: deliver MCP-lra to a discrete segment of the kidney using an ex vivo retroviral gene transfer and throughout the kidney using a lentiviral vector in vivo. We will establish the crucial period for MCP- 1 r blockade via a tetracycline transactivator system to switch delivery of MCP- ira "on and off" at stages during the progression of nephritis. 4) establish the role of chemokines that share the CCR2 with MCP-1 in MRL-Faslpr mice. We propose to compare renal disease in MRL-Faslprstrains deficient in CCR2 and MCPl to establish whether other MCPs are potential_therapeutic targets for kidney disease. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •
Project Title: COLLAGEN METABOLISM IN WOUND REPAIR Principal Investigator & Institution: Cohen, Irwin K.; Professor of Surgery (Plastic); Surgery; Virginia Commonwealth University Richmond, Va 232980568 Timing: Fiscal Year 2002; Project Start 01-DEC-1976; Project End 31-JAN-2005 Summary: (Verbatim from the applicant's abstract) Pressure ulcers are one of the most debilitating and costly problems faced by elderly and spinal cord injury patients. Treatment of this growing problem remains empirical. Progress in the development of strategies for improving treatment of pressure ulcers has been hampered greatly by the lack of a fundamental definition of the pressure ulcer microenvironment and the underlying cellular, biochemical, and molecular mechanisms responsible for the poor rate of healing of these lesions. Therefore we have pursued the hypothesis and generated extensive evidence that the chronicity of these lesions is related to the enhanced proteolytic environment associated with an over exuberant presence of polymorphonuclear leukocytes (neutrophils). Neutrophils are the predominant inflammatory cell in pressure ulcers and are a source for a number of proteinases including collagenase (MMP-8) and elastase. Recent findings based on in situ hybridization analyses, indicate that mesenchymal cells in the beds of pressure ulcers contain abundant levels of procollagen transcripts suggesting that these cells are synthetically active. Therefore, the major objective of this project will be to test the hypothesis that the excessive proteolytic environment can be diminished by good wound care and this will be associated with increased collagen matrix accumulation, and restitution of the integrity of key growth factor receptors. In addition, the hypothesis that the synthetic/degradative equilibrium of pressure ulcers can be altered using a therapeutic agent already approved for use in humans will also be tested. A longitudinal characterization of pressure ulcers will include histochemical identification of neutrophils and other cell populations, an assessment of levels and activities of proteinases that are primarily neutrophil-derived, and measurement of levels of specific proteinase inhibitors. Expression of extracellular matrix will be monitored by analyzing collagen synthesis and deposition and the location and levels of procollagen transcripts.
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Similarly, expression of growth factor receptors will be examined by qualitative and quantitative protein assessment and by in situ hybridization and quantitative ribonuclease protection assay. These data should provide key inforrnation for the development of new strategies for the treatment of pressure ulcers as well as other chronic non-healing wounds. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •
Project Title: CONDITIONAL REPLICATING ADENOVIRUS FOR GLIOMA TREATMENT Principal Investigator & Institution: Fueyo, Juan; Assistant Professor; Neuro-Oncology; University of Texas Md Anderson Can Ctr Cancer Center Houston, Tx 77030 Timing: Fiscal Year 2002; Project Start 15-AUG-2002; Project End 31-JUL-2007 Summary: (provided by applicant): Due to lack of effective therapy, primary brain tumors are the focus of intense investigation of novel experimental approaches that use vectors and recombinant viruses. Therapeutic approaches have been both indirect, whereby vectors are used, or direct to allow for direct cell killing by the introduced virus. Promising therapies can be designed by targeting fundamental molecular defects of the glioma cells. The function of p16-Rb-E2F pathway is abnormal in most malignant gliomas and therefore constitutes a suitable target for anti-cancer therapies. We have previously generated a conditional replicating adenovirus, D24, unable to bind to and inactivate the retinoblastoma protein (Rb). This tumor-selective adenovirus is able to replicate in glioma cells but not in normal cells. Although, the adenovirus induces a potent cytopathic effect in vitro, its anti-cancer effect in vivo is less dramatic. In this project, we propose a series of modifications in the D24 adenovirus in order to render the oncolytic virus more efficient infecting and killing glioma cells in vivo. In addition, experiments will be designed to introduce the necessary modifications in the D24 adenovirus to increase its specificity and to control pharmacologically its replication and spread. In vivo cancer gene therapy approaches for gliomas based on adenoviral vectormediated gene delivery and oncolytic adenoviruses can be limited by the suboptimal efficacy of adenoviruses to infect tumor cells. This issue is mainly due to deficiency of the primary adenoviral receptor on the tumor targets. To circumvent this deficiency, we propose the construction of a tumor-selective adenoviral targeted to a tumor cell marker. In this regard, RGD-related integrins are frequently overexpressed in gliomas. Furthermore, these integrins recognize the RGD peptide motif. On this basis, we will construct an adenoviral vector genetically modified to contain such a peptide within the HI loop of the fiber protein as a means to alter viral tropism. This RGD-D24 adenovirus should infect glioma cells in vivo with extraordinary efficiency, increasing dramatically the oncolytic power of the D24. In Specific Aim 1. We propose to characterize the anticancer effect of D24-RGD in vitro in comparison with D24. In Specific Aim 2, the D24-RGD construct will be characterized in vivo using an orthotopic glioma animal model. In addition, we will examine the correlation between the anti-cancer effect of the D24-RGD ant its spread throughout the tumor. The experiments will require pathological examination of the tumors, viral protein expression, as well as examination of spread of the virus throughout the tumor. We will asses the replication of the virus within the tumor and titer the viral production in vivo. Finally, we will analyze how the administration of anti-adenoviral drugs influence the growth of D24-RGD-infected tumors. In Specific Aim 3, we will combine a high-effective oncolytic adenovirus with a regulatory system that can be used to control viral replication in vivo in a selected site and at a desired time. The D24-RGD construct will be genetically modified to include drug response elements sensitive to the effect of tetracycline. To obtain tissue-specific
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expression of the target gene, we will coupled the regulator to a cancer specific (E2F-1) promoter to drive the early viral genes. The combination of an inducible system and a tissue-specific promoter will allow the development of an innovative oncolytic system, which is able to kill cancer cells and spread within the tumor in a cell type-specific and time- and level-controllable fashion. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •
Project Title: CONNEXIN43 MORPHOGENESIS
LOSS-OF-FUNCTION
AND
CARDIAC
Principal Investigator & Institution: Gutstein, David E.; Medicine; Mount Sinai School of Medicine of Nyu of New York University New York, Ny 10029 Timing: Fiscal Year 2002; Project Start 12-JAN-2000; Project End 31-JUL-2002 Summary: Connexin43 (Cx43) is the most abundant gap junction protein in the heart and plays a critical role in heart development. Cx43-/- mice develop right ventricular outflow tract (RVOT) obstruction in utero and die of pulmonary oligemia shortly after birth. The molecular mechanisms, the critical period in heart development and the specific cell lineages responsible for the defect in heart formation are unknown. We hypothesize that the Cx43-/- phenotype results from a primary developmental defect in cells of neural crest origin, rather than in the myocytes themselves. Furthermore, we hypothesize that the loss of Cx43 results in dysregulated cell proliferation, a phenomenon that may underlie the disordered neural crest-derived tissue growth causing RVOT obstruction in Cx43-/- mice. To test these hypotheses, we will conditionally inactivate the Cx43 gene in a lineage-specific manner. We predict, according to our hypothesis, that targeted inactivation of the Cx43 gene in cells of neural crest origin will recapitulate the phenotype of the Cx43-/- mouse. For this proposal, we have engineered murine embryonic stem (ES) cells to harbor loxP sites flanking the Cx43 open reading frame (floxed) for Cre recombinase-mediated inactivation of the Cx43 gene. We have established that our lines of targeted ES cells express wildtype levels of Cx43 mRNA and protein. In addition, upon transfection with a vector containing the Cre cDNA or infection with a Cre-expressing adenovirus, the floxed Cx43 gene recombines and is inactivated as predicted. As a result, we have generated chimeric mice carrying the mutated Cx43 allele with one of our targeted ES cell lines. Using these reagents, we propose to study, through inducible loss-of-function experiments, whether a specific lineage is responsible for the Cx43-/- developmental phenotype. Growth and differentiation characteristics of Cx43-/- ES cells and proliferation of Cx43-/- cells in chimeric mice will also be studied. In order to determine when Cx43 is required during embryogenesis, we are developing a novel, reversible, tetracycline (TCN)-regulated "knock-in" system to control endogenous Cx43 gene expression. The proposed experiments promise to provide novel information delineating the molecular mechanisms by which loss of Cx43 results in cardiac dysmorphogenesis. These results will add important information to our knowledge of developmental biology, while also elucidating potential mechanisms of congenital heart disease. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •
Project Title: CONTROL OF THE METASTATIC PROGRESSION OF PROSTATE CANCER Principal Investigator & Institution: Lokeshwar, Balakrishna L.; Associate Professor; Urology; University of Miami-Medical Box 248293 Coral Gables, Fl 33124 Timing: Fiscal Year 2003; Project Start 01-APR-1994; Project End 31-JUL-2007
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Summary: (provided by applicant): Effective treatments for controlling prostate cancer metastasis are not yet available. Investigations of this and other metastatic cancers have revealed stromal-induced factors that confer "acquired drug resistance". In prostate cancer, stromal factors induce pro-inflammatory cytokines, IL-1beta, IL-6 and IL-8 production in tumor cells. This coincides with increased resistance to cytotoxic/antimetastatic drugs, such as doxorubicin, and CMT-3 (a novel cytotoxic and anti-metastatic tetracycline analog). Blocking IL-1beta and IL-6 production by antisense cDNA transfection sensitizes tumor cells to chemodrugs, whereas, blocking IL-8 production decreases their invasive potential. A combination of cytotoxic and anti-inflammatory drugs reduces the expression of these cytokines. Thus, a combination therapy that inhibits cytokine production during an inflammatory response to chemotherapy should improve the efficacy of cytotoxic and anti-metastatic drugs. The goals of this proposal are: 1. To establish a cause and effect relationship between tumor cell-associated cytokine production and acquired drug resistance, as well as, tumor progression. (2) Evaluate the efficacy of combined cytotoxic and anti-inflammatory drugs to control metastatic prostate cancer. A cause-effect relationship between cytokine production and tumor progression will be established by investigating, in xenografts, the growth and metastasis of prostate cancer cells (PC-3ML and LNCaP), expressing green fluorescence protein and cDNA -sense and anti-sense constructs of IL-1beta, IL-6 or IL-8. Possible interlinked roles of these 3 cytokines will be investigated by characterizing double transfectants of PC-3ML expressing IL-1beta antisense/IL-6sense and IL-1beta sense/IL8antisense cDNAs (Aim 1). Alterations in drug-induced cytotoxicity in PC-3ML and LNCaP transfectants, selectively altered in cytokine production, will be studied by cytotoxicity assays, cDNA microarray analysis, followed by RT-PCR and protein ELISAs. Drug-induced changes in stromal factors responsible for altering drug sensitivity will also be examined (Aim 2). The efficacy of a combination of a cytotoxic/anti-metastatic drug (i.e., CMT-3) and an anti-inflammatory drug (i.e., Celecoxib) will be tested in PC-3ML and LNCaP cytokine transfectants in xenografts. (Aim 3). The proposed study should reveal the role of cytokines in acquired drug resistance and prostate cancer progression. It will also establish whether a combined cytotoxic and anti-inflammatory therapy will be more effective in controlling metastatic prostate cancer. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •
Project Title: CORE--TRANSGENIC MOUSE Principal Investigator & Institution: Klement, John F.; Assistant Professor; Thomas Jefferson University Office of Research Administration Philadelphia, Pa 191075587 Timing: Fiscal Year 2002; Project Start 10-MAY-2002; Project End 31-MAR-2007 Summary: (provided by applicant): The purpose of this application is the incorporation of a Transgenic Mouse Core in the renewal of Dr. Sergio Jimenez's Program Project grant. In this grant, Dr. Jimenez is joining with the Dermatology Animal Core to produce animal models of human disease and to use transgenic mice to study protein structure and function in bone and cartilage. The procedures used by the Core to generate transgenic mice are pronuclear injection and gene-targeting technologies. Specifically, it is proposed to generate mutations in the gene for the transcription factor, COMP, using gene-targeting procedures. Mutations will also be generated in the collagen type II gene (COL2A1) in order to study structure/function relationships of this collagen as it interacts with other proteins. For introducing the site-specific mutations into these genes, the double-replacement technique is proposed, as well as alternate mutagenesis strategies. Techniques are proposed to generate transgenic mice
18
Tetracycline
that will express a transgene in a temporal and spatial-specific manner using an inducible expression system such as the Tetracycline control system. It is proposed to utilize the collagen type II promoter to drive an inducible transcription factor of the TetON system (rtTA) to generate tetracycline inducible expression of a mutated1(II) collagen gene. Other methods, which may be employed, are the generation of conditional null, or dominant negative, phenotypes utilizing the Cre/Lox system. No human patients will be involved in the Core's studies. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •
Project Title: DEVELOPMENT OF A SAFER SMALLPOX VACCINE Principal Investigator & Institution: Jacobs, Bertram L.; Professor; Microbiology; Arizona State University P.O. Box 873503 Tempe, Az 852873503 Timing: Fiscal Year 2003; Project Start 30-SEP-2003; Project End 31-MAR-2008 Summary: Replication competent vaccinia virus (W), the current vaccine for smallpox, can cause severe complications after vaccination, especially in immune suppressed individuals. We are seeking to develop strains of VV that are replication competent, and thus will induce a strong immune response, without the complications associated with vaccination with the current vaccines. Thus, the Aim of this proposal is to prepare conditional mutants of VV that are either dependent on an FDA-approved drug for replication, or are treatable by an FDA-approved drug. For drug-sensitive viruses, individuals who experience complications could be treated with the FDA-approved drug. For drug-dependent viruses, should complications arise, the drug could be withdrawn from vaccinated individuals as a treatment. Drug-dependent viruses have the added advantage that they would not be able to spread in a viable form from vaccinated individuals to contacts. The relative immunogenicity and safety of these two strategies will be compared with that of a current vaccine (Dryvax) in immunocompetent mice (immunogenicity and safety), and in immunodeficient SCID mice (safety only). The most promising of these strains will be engineered into a virus background suitable for use in humans, prepared under GMP conditions and tested in chimpanzees and humans for safety and immunogenicity, compared to Dryvax. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen
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Project Title: DIFFERENTIATING AGENTS IN HEMATOLOGIC MALIGNANCIES Principal Investigator & Institution: Kufe, Donald W.; Professor; Dana-Farber Cancer Institute 44 Binney St Boston, Ma 02115 Timing: Fiscal Year 2002; Project Start 01-AUG-1986; Project End 31-JAN-2007 Summary: (provided by applicant): Certain phorbol esters, polar solvents and retinoids have been identified as in vitro and in vivo inducers of human myeloid leukemia cell differentiation. These findings have indicated that factor-independent growth of myeloid leukemia cells is reversible. The mechanisms by which these agents induce terminal differentiation, however, are unknown. Our work has focused on induction of the stress activated protein kinase (SAPK/JNK) as a signal that directs cellular differentiation. The results indicate that SAPK activates the c-jun and EGR-1 early response genes and thereby in part the differentiated phenotype. SAPK also targets the release of mitochondrial cytochrome c to integrate apoptosis with terminal differentiation. Our studies have shown that activation of protein kinase C-beta (PKCbeta) in the response to phorbol esters is essential for induction of SAPK and differentiation. PKC-beta-mediated signals induce the production of reactive oxygen species (ROS) and thereby the activation of SAPK. The findings also demonstrate that
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PKC-beta and the related PKC-beta isoform are each targeted to the nucleus and mitochondria in the phorbol ester response of myeloid leukemia cells. The proposed work will extend these studies by defining the effectors downstream to PKC-beta and PKC-beta that regulate the differentiation program. Our hypothesis is that PKC-betaand PKC-beta-activated pathways function in concert to integrate nuclear and mitochondrial signals that confer terminal differentiation. The Specific Aims are: 1) To further define PKC-beta- and ROS-dependent activation of SAPK in TPA-induced nuclear and mitochrondial signaling; 2) To study the functional significance of targeting PKC-beta to the nucleus and mitochrondial in the induction of myeloid leukemia cell differentiation; 3) To define the role of PKC-beta in nuclear and mitochondrial signaling associated with terminal differentiation; and 4) To study integration of the differentiated phenotype with apoptosis in the induction of terminal differentiation. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •
Project Title: DROSOPHILA DNA REPLICATION ORIGINS Principal Investigator & Institution: Tower, John G.; Associate Professor; Biological Sciences; University of Southern California 2250 Alcazar Street, Csc-219 Los Angeles, Ca 90033 Timing: Fiscal Year 2002; Project Start 01-APR-2002; Project End 31-MAR-2006 Summary: (provided by applicant): The long term objective of this research is to understand how the higher eukaryotic cell designates certain regions of chromosomal DNA as replication origins, and regulates the firing of these origins in a tissue- and temporal-specific manner. The model system being utilized is the developmentally regulated amplification of the chorion gene clusters in Drosophila ovarian follicle cells. The control of DNA replication is particularly relevant to the study of human cancers. Several proto-oncogenes and tumor-suppresser genes are implicated in the regulation of DNA replication. We have identified two distinct cis-regulatory elements involved in DNA replication: replicators and origins. These will be studied by mutating the chorion gene locus in vitro, reintroducing the mutated constructs into the chromosomes of transgenic animals, and assaying the ability of the constructs to amplify using simple quantitative Southern blots. 2-Dimensional gel electrophoresis of DNA replication intermediates isolated from the ovarian follicle cells allows the specific sequences acting as origins to be identified. The origins can be distinguished from essential sequences called replicators which act in cis to regulate the origins. We hypothesize that unique sequence element(s) "X" are part of the replicator and/or origin(s), and mark the chorion loci for amplification by interacting with one or more "factors X." Two proteins required in trans for amplification are being analyzed, k43 (dmORC2) and chiffon. Both proteins may interact with or be part of factor X. Finally, novel genetic methods will be used to identify additional trans regulators of amplification including factor X. The first method uses an engineered transposable element to generate dominant, conditional (tetracycline-dependant) mutations at high frequency. The second method involves tetracycline-regulated expression of double-strand RNA, which in turn causes sequencespecific inhibition of gene expression. The experiments will test a number of specific hypotheses as to the organization and regulation of the chorion locus DNA replication origins. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen
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Project Title: DYSTROPHIN REPLACEMENT IN MDX MICE Principal Investigator & Institution: Chamberlain, Jeffrey S.; Professor; Neurology; University of Washington Grant & Contract Services Seattle, Wa 98105
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Timing: Fiscal Year 2002; Project Start 01-APR-1991; Project End 31-MAR-2005 Summary: (Adapted from applicant's abstract): Duchenne muscular dystrophy (DMD) is an X-linked recessive, lethal disorder caused by mutations in the dystrophin gene. Considerable progress has been made both in understanding the function of dystrophin, and in demonstrating the feasibility of gene therapy for DMD. Nonetheless, numerous obstacles remain before gene therapy can be effectively applied to this common genetic disease. These obstacles include a lack of data on the reversibility of the dystrophic pathology, limited ability of viral vectors to carry the enormous dystrophin gene or cDNA, and questions about the effectiveness of inefficient delivery methods of dystrophin vectors. This application proposes to address these concerns by generating several novel strains of transgenic mice. The ability to modulate the dystrophic phenotype will also be explored using viral delivery of dystrophin and several death protectors to mdx mice, a model for DMD. Transgenic mice that express moderate levels of dystrophin are able to prevent the development of dystrophy in the mdx mouse, a model for DMD. Delivery of adenoviral vectors expressing truncated dystrophins to neonatal, immune tolerant mice can also prevent muscular dystrophy near the site of injection. However, it has not been possible to demonstrate that the pathology can be halted or reversed in adult, dystrophic animals. Aim1 will address the feasibility of reversing muscular dystrophy at different stages of the disease by studying a transgenic mouse line that displays tetracycline-inducible dystrophin expression. Aim 2 will continue previous work aimed at understanding the structural basis of dystrophin functional domains, with the goal of developing severely truncated cDNAs that can be carried by a variety of promising viral vectors, such as adenoassociated viruses (AAV). Currently, the only vectors capable of carrying the full-length dystropin cDNA have problems with cytotoxicity, immune rejection or low titers. AAV efficiently infect muscle with no immune response, but have a limited cloning capacity. Aim 3 explores the ability to modulate dysrtophy by delivery of dystrophin with proteins that repress apoptosis and/or enhance muscle regeneration. Achieving uniform and efficient gene delivery to muscles using viral vectors is a daunting goal. The ability to modulate dystrophy and prolong muscle fiber longevity could greatly facilitate the effectiveness of dystrophin gene replacement strategies. These studies will provide new insights into both the structure of dystrophin and the mechanisms of dystrophic cell death and will help advance the development of gene therapy. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •
Project Title: EMBRYOID BODY-DERIVED HEMATOPOIETIC STEM CELL LINES Principal Investigator & Institution: Hawley, Robert G.; Head; American National Red Cross Rockville, Md 20855 Timing: Fiscal Year 2002; Project Start 15-AUG-2001; Project End 31-JUL-2006 Summary: The establishment of hematopoiesis in culture from murine embryonic stem (ES) cells provides a powerful approach for studying early commitment steps as hematopoietic precursors develop from pre-hematopoietic mesoderm. Analysis of developing embryoid bodies has demonstrated that hematopoietic differentiation in these cultures recapitulates many aspects of the onset of hematopoiesis in utero, including vasculogenesis and the switch from the primitive to the definitive program. We previously used CCE ES cells transduced with our MSCV retroviral vector overexpressing the diverged homeobox gene HOX11 of T-cell acute lymphoblastic leukemia to establish factor-dependent hematopoietic precursor cell lines arrested at novel stages of primitive and definitive hematopoietic development. These results, demonstrating proof-of-concept, provide the rationale for the present proposal to extend
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this strategy to obtain conditionally-blocked murine hematopoietic precursor cell lines with a variety of differentiative potentials. We are particularly interested in the possibility of conditionally arresting common endothelial/hematopoietic precursors (i.e., hemangioblasts) as well as hematopoietic stem cells with long- term in vivo repopulating activity. To this end, our specific aims are to develop two systems for conditional immortalization: the first, based on site-specific excision of HOX11 by adenovirus-mediated transient expression of Cre recombinase; and the second, based on a tetracycline-regulatable HOX11 retroviral vector. While both approaches will permit precursor-progeny relationships to be unequivocally established, we hypothesize that the latter strategy will allow clonal descendants of precursor cells to be arrested and amplified at successive stages of the hematopoietic hierarchy. It is envisioned that the multipotent precursor lines obtained will have broad utility for molecular biological investigations of hematopoietic differentiative progression and lineage restriction. Toward this goal, homogenous populations of clonally-related precursor cells will be used as starting material for identification by cDNA microarray technology of differentially expressed genes as candidate regulators of hematopoietic cell fate decisions. It is anticipated that the information gained from these studies will also provide insight into the potential roles of those homeobox genes implicated in the transcriptional control of hematopoiesis as well as lead to a better understanding of the underlying mechanism of leukemia initiation mediated by HOX11. Successful realization of these goals will provide a basis for future research endeavors involving primate ES cells. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •
Project Title: ENHANCED HSV-1 VECTOR PARTICLES FOR NEURAL GENE THERAPY Principal Investigator & Institution: Geller, Alfred I.; Assistant Professor; Medicine; Harvard University (Medical School) Medical School Campus Boston, Ma 02115 Timing: Fiscal Year 2002; Project Start 01-AUG-2001; Project End 31-JUL-2005 Summary: This laboratory has developed a helper virus-free Herpes Simplex Virus (HSV-1) plasmid vector system for gene transfer into neurons. Using this system, we have begun to explore gene therapy approaches to specific neurological disorders, such as Parkinson's Disease (PD). We have shown that delivery of a HSV-1 vector that expresses human tyrosine hydroxylase into the partially denervated striatum in the 6hydroxydopamine rat model of PD results in significant (64 percent) and long-term (1 year) behavioral recovery. Modifications to the vector particle have enhanced the utility of specific vector systems. First, the titers and infectivity of classical retrovirus vectors, lentivirus vectors, and other vector systems have been enhanced by pseudotyping with vesicular stomatitis virus (VSV) G protein. Recently, both we and other investigators have shown that HSV-1 vectors can be pseudotyped with VSV G protein and such vector particles can support gene transfer into neurons in the rat brain. Second, gene transfer has been targeted to specific types of cells by modifying the vector particle of classical retrovirus vectors or adenovirus vectors. Third, we have enhanced neural gene transfer and long- term expression by packaging vectors in the presence of mutations in specific HSV-1 proteins that affect the virion. The long-term goal of this proposal is to modify the HSV-1 vector particle to enhance its utility for human gene therapy of neurological disorders such as PD. The first specific aim will develop procedures for producing high titer HSV-1 vectors pseudotyped with VSV G protein. The second specific aim will target gene transfer to nigrostriatal neurons by modifying the HSV-1 vector particle to bind to specific receptors on these neurons. The third specific aim will
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enhance gene transfer and long-term expression by packaging vectors in the presence of mutations in specific HSV-1 proteins that affect the virion. These modified vector particles will be systematically characterized and then evaluated for gene transfer and expression in the rat brain. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •
Project Title: ENZYME AND GENE THERAPY OF MPS I IN ANIMAL MODELS Principal Investigator & Institution: Neufeld, Elizabeth F.; Professor and Chair; Biological Chemistry; University of California Los Angeles 10920 Wilshire Blvd., Suite 1200 Los Angeles, Ca 90024 Timing: Fiscal Year 2002; Project Start 01-AUG-1987; Project End 31-JUL-2004 Summary: The molecular basis of Mucopolysaccharidosis I (MPS I, Hurler, Hurler/Scheie and Scheie syndromes) is mutations in the gene encoding alpha-Liduronidase, resulting in absence of enzyme activity, accumulation of undegraded glycosaminoglycans, and systemic disease. Because alpha-L-iduronidase, a lysosomal enzyme, can be secreted as well as taken up by receptor-mediated endocytosis, MPS I has long been considered a prime candidate for replacement therapy. Alpha-LIduronidase provided by donor cells of hematopoietic origin (probably macrophages) is thought to be responsible for changes in disease progression that are seen after bone marrow transplantation. The course of the disease can also be altered by administration of recombinant alpha-L-iduronidase. The therapeutic effect of the enzyme previously observed in the canine MPS I model had been promising enough to generate a clinical trial in MPS I patients. But even though recombinant alpha-L-iduronidase may soon become available as a pharmaceutical, there is still a need for developing effective and long-lasting gene therapy. To have a suitable animal model, we have produced mutant mice by targeted disruption of the alpha-L-iduronidase gene. Aim 1 is to define the phenotype of the MPS I mouse model at the biochemical, pathological, behavioral and clinical levels. Aim 2 is to determine the effect of administration of human recombinant alpha-L-iduronidase on the disease phenotype, in order to provide a basis of comparison for gene-based procedures. Aim 3 is to compare transplantation of genemodified bone marrow over-expressing human alpha-L-iduronidase with transplantation of bone marrow expressing normal levels of the enzyme, for effectiveness in altering the disease phenotype. Aim 4 is to determine the effectiveness of tetracycline-inducible alpha-L-iduronidase expression in macrophages as a means of enzyme delivery to affected organs, in particular to the brain, as well as to compare it with the above procedures for ability to alter the disease phenotype. The proposed studies represent steps in our long-term program to develop treatment for patients affected with MPS I. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen
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Project Title: EPITHELIAL CELL POLARITY IN POLYCYSTIC KIDNEY DISEASE Principal Investigator & Institution: Weimbs, Thomas; Assistant Professor; Cleveland Clinic Foundation 9500 Euclid Ave Cleveland, Oh 44195 Timing: Fiscal Year 2002; Project Start 01-JUL-2002; Project End 31-MAY-2007 Summary: (provided by applicant): Autosomal dominant polycystic kidney disease (ADPKD) is one of the most common genetic diseases worldwide. Mutations in the PKD1 or PKD2 genes lead to phenotypic changes in affected renal epithelial cells that include increased proliferation and apoptosis, defects in protein trafficking and changes in transepithelial transport functions. This leads to the formation of large renal cysts, the
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destruction of the normal renal tissue and finally renal failure. Since the functions of the PKD1/2 gene products, polycystin-1 and polycystin-2, are currently unknown, the rational design of strategies for therapeutic intervention has been difficult. This research proposal seeks to close the gap in our knowledge on what lies between PKD1 gene mutations and the epithelial phenotype that finally leads to cyst formation. We have developed an in vitro cell culture system in the polarized renal epithelial cell line MDCK for the tetracycline-regulated expression of polycystin-1 domains that are proposed to act as dominant-negative inhibitors of the endogenous protein. Preliminary results show that this leads to the induction of several of the typical phenotypes of authentic cystic epithelial cells in ADPKD such as increased proliferation, apoptosis and apical mistargeting of the EGF receptor. The molecular mechanisms that lie downstream of the polycystin-1 defect and are responsible for these phenotypes will be identified and their relationship to each other defined. Proteins that interact with the dominant-negative polycystin-1 domains to mediate these mechanisms will be identified. Of particular importance is the investigation of defects in intracellular membrane trafficking that have been proposed to be responsible for several of the final phenotypes of cystic epithelial cells. Preliminary results from this laboratory suggest that specific changes in the SNARE membrane fusion machinery are involved in membrane trafficking defects ADPKD. The role of these SNARE changes in the acquisition of the cystic epithelial phenotype, and how they are caused by polycystin-1 disruption will be investigated. These studies will help to define the normal function of polycystin-1 and the downstream effects that result from its disruption. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •
Project Title: ANTIGEN
FUNCTION
OF
DESMOGLEIN
1/PEMPHIGUS
FOLIACEUS
Principal Investigator & Institution: Green, Kathleen J.; Professor; Pathology; Northwestern University Office of Sponsored Research Chicago, Il 60611 Timing: Fiscal Year 2002; Project Start 01-AUG-1993; Project End 31-JUL-2007 Summary: (provided by applicant): Desmogleins are members of the cadherin superfamily of cell adhesion molecules. Along with desmocollins (Dscs), desmogleins (Dsgs) make up the adhesive core of the desmosome through their extracellular domains, and anchor intermediate filaments to the plasma membrane through interactions between their cytoplasmic domains and armadillo/plakin proteins. Autoantibodies directed against desmogleins are causative in the blistering diseases known as pemphigus; however, the molecular mechanism underlying pathogenesis in pemphigus is poorly understood. Furthermore, there are three Dsg genes and three Dsc genes, expressed in a differentiation-dependent manner in the epidermis, and it is unclear why multiple genes are required. To understand the underlying basis of human autoimmune and inherited disorders targeting the desmogleins, it will be crucial to determine the functions of desmosomal cadherins as well as how the adhesive complex is assembled, maintained and regulated. Our aims for the next funding period are: 1) To determine the molecular basis of desmosomal cadherin-mediated adhesion and pairing preferences for Dscs and Dsgs by using a tetracycline-regulatable system in which adhesive function can be reconstituted in L929 cells, and to develop this system into a test for the pathogenic activity of pemphigus antibodies, 2) To determine how Dsgs/Dscs collaborate with armadillo proteins to form distinct, differentiation-specific protein complexes using a combination of in vitro and high resolution structural studies to establish the identity and affinity of desmosomal cadherin-armadillo binding partners, and cellular reconstitution techniques to determine how interactions translate
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into structurally distinct desmosomes, 3) To determine how desmosomal cadherins and their associated proteins are coordinated spatially and temporally during their assembly into keratinocytes by time lapse analysis of living cells using fluorescently-labeled probes, and 4) To determine the function of Dsg1 and biological significance of Dsg1 as a caspase substrate for keratinocyte adhesion, differentiation and apoptosis by defining UV-dependent Dsg1 processing events that occur in vitro and in cultured keratinocytes and by defining the roles of wild type Dsg1 its cleavage products and cleavage resistant forms during differentiation in cultured human keratinocytes and transgenic mice. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •
Project Title: FUNCTIONAL GENOMICS OF HEARING Principal Investigator & Institution: Chen, Zheng-Yi; Assistant Professor; Massachusetts General Hospital 55 Fruit St Boston, Ma 02114 Timing: Fiscal Year 2002; Project Start 01-APR-2001; Project End 31-MAR-2006 Summary: In this application we propose to use microarray technology to study genes controlled by Brn-3.1, a hair-cell- specific transcription factor. The traditional way of studying transcription factor targets has been time consuming and laborious. It also lacks a means of simultaneously isolating multiple genes under the control of, a transcription factor. The microarray approach provides an ideal route for such a task. In addition the combination of human and other genome projects along with microarray technology should shed light on functional pathways controlled by Brn-3.1 and other transcription factors. Three major studies will be carried out. The first is to use three complementary approaches, based on the oligonucleotide array technology, to isolate candidate genes controlled by Brn- 3.1. The tetracycline induction of Brn-3.1 in a human osteosarcoma cell line will provide robust control of production of Brn-3.1, and allow us to survey the greatest number of human genes (35,000) for Brn-3.1 targets. The transfection of the organ of Corti cell line will likely identify the targets which may require the co-factors for Brn-3.1 regulation. The comparison of expression profiles of Brn-3.1 knock-out mouse utricles with control may reveal both direct and in-direct target genes regulated by Brn-3.1. The combination of these approaches will build enough redundancies to ensure the isolation of the candidate genes. The second aim is to systematically characterize the activation and binding on the regulatory regions of candidate genes by Brn- 3.1. Cluster analysis will be used to identify the expression pattern of candidate genes during development. Other genes in the clusters will be examined for the binding site of Brn-3.1 such that more candidate genes will emerge. In addition the 5' regulatory regions of the genes within the same cluster as Brn- 3.1 targets will be examined to identify the shared binding motifs for other important transcription factors. In the third aim of the grant the target genes will be studied in relation to their expression in the hair cell of normal and Brn- 3.1 knock-out mice; in order to provide the casual relation between their expression and the onset of Brn-3.1. Antibodies will be used to localized the proteins in the hair cells. The success of the project will provide information regarding genes and their functional pathways controlled by Brn-3.1, and should establish a model for studying hair cell development controlled by other transcription factors such as Math1. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen
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Project Title: GENE THERAPHY FOR PARKINSON'S DISEASE Principal Investigator & Institution: Bohn, Martha C.; Director of the Neurobiology Program; Children's Memorial Hospital (Chicago) Chicago, Il 606143394
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Timing: Fiscal Year 2002; Project Start 01-SEP-1996; Project End 31-MAR-2005 Summary: (Verbatim from the Applicant's Abstract) The long-term goal of this project is to develop novel gene therapies for neurodegenerative diseases. In the previous support period, we focused on adenoviral (Ad) vectors to deliver the gene encoding GDNF (glial cell line-derived neurotrophic factor). Ad-GDNF injected into either the substantia nigra or striatum of a progressive degeneration model of Parkinson's disease protected dopaminergic (DA) neurons against cell death induced by the neurotoxin 6-OHDA. AdGDNF injected into the striatum also prevented the acquisition of behaviors and molecular changes that occurred in DA deficient young and aged rats. This proposal focuses on the hypothesis that anti-apoptotic gene delivery will also protect DA neurons in vitro and in vivo and have a synergistic effect with delivery of neurotrophic factor genes. Viral vectors harboring genes that block specific apoptotic death pathways, including XIAP, a dominant-negative caspase-9, bcl-2 and bclxl will be studied for effects on survival and function of DA neurons either alone or in combination with neurotrophic factors, GDNF or neurturin. Genes will be delivered to DA neurons in culture and in rat brain using helper free HSV:AAV hybrid amplicon vectors. These vectors will incorporate bidirectional expression cassettes that drive both the therapeutic gene and the cellular marker gene, green fluorescent protein, to permit specific evaluation of transduced cells. Expression will be controlled using the tetracycline responsive element such that transgene expression is "on" in the presence of tetracycline activator (TA) and in the absence of doxcycline (Dox). Vectors will be made in which TA is driven by a viral promoter of the DA cellular promoter, tyrosine hydroxylase (TH). Effects of the 'therapeutic' genes will be studied using non-neuronal cells, the DA cell line, MN9D, and primary fetal DA neurons treated with the neurotoxins, MPP+ or 6OHDA or other cellular insults. In vivo effects of therapeutic genes will be studied in: 1) rats that have received grafts of fetal DA neurons, and 2) rats that have received a progressive 6-OHDA lesion of the nigrostriatal projection. Reversibility of effects will be studied by administration of Dox. Effects on DA neurons will be evaluated using quantitative morphometric and molecular techniques and behavioral evaluations. This project also aims to continue its evaluation of new generation viral vectors, including E2b deleted Ad, totally gutted Ad, and HSV:AAV amplicon, for stability and levels of expression in the nigrostriatal system. The studies involve collaborations among investigators at Children's Memorial Hospital and Northwestern Univ. Med. School and are relevant to the development of novel therapies for neurodegenerative diseases and injuries to the CNS. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •
Project Title: DISORDERS
GENE
THERAPY
FOR
CHRONIC
NEURODEGENERATIVE
Principal Investigator & Institution: Castro, Maria G.; Professor; Cedars-Sinai Medical Center Box 48750, 8700 Beverly Blvd Los Angeles, Ca 900481804 Timing: Fiscal Year 2002; Project Start 01-AUG-2002; Project End 31-JUL-2007 Summary: (provided by applicant): Parkinson's disease (PD) is a chronic neurodegenerative disorder. Although we do not yet understand its cause, there is extensive degeneration of nigro-striatal DA neurons. Powerful neurotrophic factors which could be used for the treatment of PD, like GDNF, have been described recently. The ultimate goal of this proposal is to develop novel high-capacity adenoviral systems for cell-type specific, inducible, long term, stable, and non-immunogenic delivery of neuroprotective genes to the brain for both experimental transgene expression in adult animals, and for the future treatment of chronic neurodegenerative diseases such as PD
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and Alzheimer's disease by gene therapy. Currently the use of adenovirus vectors has been limited by the low efficiency of transcriptional promoter elements currently used, which directly leads to the need to use higher doses of vectors, and the cytotoxicity and immunogenicity of viral proteins expressed from the genornes of first generation adenoviral vectors. We now wish to develop novel cell-type specific and inducible vectors, that will allow efficient, safe, and long-term gene delivery vectors for neurological gene therapy. We will construct high-capacity helper-dependent adenoviral vectors that express no adenoviral genes. We will utilize the powerful, astrocyte specific major immediate early murine Cytomegalovirus promoter, driving novel tetracycline-dependent transcriptional activators to achieve cell-type specific and regulatable expression of GDNF. The efficacy, cell-type specificity, and inducibility of these vectors will be tested stringently to assess their capacity to deliver cell-type specific and regulatable GDNF, and also to determine any potential side effects caused either by the vectors or the long term expression of powerful neurotrophic agents. The reagents and principles established by this work will be of substantial value to those with interests in the basic and clinical neurosciences, and will lead to the development of novel, efficient, and safe approaches for the treatment of human chronic neurodegenerative diseases. This research will facilitate the development of the tools needed to achieve long-lived, safe, cell-type specific, regulatable, non-cytotoxic transgene expression, and, ultimately, for the treatment of patients suffering from chronic neurodegenerative diseases. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •
Project Title: GENETIC SYSTEMS FOR FUSOBACTERIUM NUCLEATUM Principal Investigator & Institution: Haake, Susan K.; Assistant Professor; Periodontics; University of California Los Angeles 10920 Wilshire Blvd., Suite 1200 Los Angeles, Ca 90024 Timing: Fiscal Year 2002; Project Start 01-JUN-1998; Project End 31-MAY-2004 Summary: (Adapted from investigator's Abstract): Fusobacterium nucleatum is an important pathogen that is commonly involved in periodontal disease and other common human infections. Little is known about the virulence mechanisms of this pathogen and investigation has been hampered by a lack of systems for genetic manipulation. The importance of F. nucleatum in oral and systemic diseases has led to interest in genomic sequencing within the next few years. Systems for molecular analysis will be required to effectively utilize sequence data in the study of virulence properties. The Principal Investigator's laboratory has recently isolated and characterized a F. nucleatum plasmid, pFN1. In this proposal, the hypothesis to be tested is that pFN1 can be used to develop a system of gene transfer as well as a host vector system for the application of molecular techniques in F. nucleatum. In Specific Aim 1 a gene transfer system for F. nucleatum will be developed using electroporation with pFN1-based plasmids that encode a tetracycline selectable marker. Transformation studies will identify a "first generation" shuttle plasmid, a F. nucleatum strain with high transformation efficiency, and additional antibiotic resistance determinants that confer a selectable phenotype in F. nucleatum. The gene transfer system will be optimized in Specific Aim 2 through refinement of both the shuttle plasmid and the transformation procedures. Characterization of the pFN1-based plasmids will include confirmation of the theta mechanisms of replication, and determination of segregational and structural stability, the pFN1 minimal replicon, and the plasmid copy number. A "second generation" plasmid will be developed by eliminating nonessential regions of the pFN1 DNA. The efficiency of transformation will be optimized with the second generation
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shuttle plasmid and evaluated in representative F. nucleatum strains. A chromosomal integration plasmid for F. nucleatum, which lacks a F. nucleatum replicon but contains F. nucleatum genomic DNA sequences and a tetM determinant, will be developed in Specific Aim 3. The genomic organization of transformants will be evaluated by Southern and PCR analyses to confirm the chromosomal integration, and to characterize the site and mechanism of integration. The results of these studies will create the foundation for genetic analysis in F. nucleatum by developing molecular techniques of mutagenesis and complementation. Because systems of gene transfer are not currently available for F. nucleatum, these results will have significant impact on our understanding of F. nucleatum virulence and potentially in the prevention of human infectious diseases. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •
Project Title: GENETICALLY ENGINEERED ANTI ANGIOGENIC ANTI GLIOMA CTL'S Principal Investigator & Institution: Carter, Bob S.; Massachusetts General Hospital 55 Fruit St Boston, Ma 02114 Timing: Fiscal Year 2002; Project Start 14-AUG-2000; Project End 31-JUL-2005 Summary: The long term goal of this project is to develop new therapies for the treatment of malignant glioma based on the development of immune effector cells with genetically engineered novel targeting and effector functions. It is hypothesized that T cells and potentially other effector cells can be engineered to directly recognize and kill the both the developing tumor vasculature and tumor cells themselves. This shall be accomplished through the use of gene transfer vectors that encode chimeric T cell receptors (cTCR) directed against specific endothelial cell surface receptors and glioma related tumor neoantigens. Retroviral gene transfer will also be used in an attempt to generate genetically-modified T cells which allow for the expression of additional functions including co-stimulation, tetracycline responsiveness, and release of specific gene products with potent anti-angiogenic activity. The activity of T cells transduced by the different vectors will be characterized in vitro for their target cell specificity and cytolytic function and, subsequently for anti-tumor activity in several different preexisting tumor models including intracerebral models. In addition to assessing the therapeutic efficacy of the transduced cells, we will characterize the persistence and trafficking characteristics of the transplanted cells. We will also compare the anti-tumor activity achieved by adoptive transfer of genetically modified T cells to that achieved by the engraftment of lethally irradiated recipients by hematopoietic stem cells transduced by the chimeric T cell receptor vectors. This project shall provide the candidate with a research foundation in gene transfer technologies, tumor immunotherapy, and antiangiogenesis as part of a long-term strategy to develop translational therapies for the treatment of cerebral glioma in man. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen
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Project Title: GI CARDIOPROTECTION
SIGNALING
IN
CARDIOMYOPATHY
AND
Principal Investigator & Institution: Baker, Anthony J.; Associate Professor; Northern California Institute Res & Educ 4150 Clement Street (151-Nc) San Francisco, Ca 941211545 Timing: Fiscal Year 2002; Project Start 01-AUG-2002; Project End 31-JUL-2007
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Summary: (provided by applicant): In humans, chronically increased signaling through Gi-coupled receptors is associated with congestive heart failure (CHF) caused by idiopathic dilated cardiomyopathy or ischemic cardiomyopathy following myocardial infarction. However, the mechanisms responsible are unclear. Our working hypothesis is that chronically increased Gi signaling causes impaired excitation-contraction (ec) coupling. To test this hypothesis we will combine physiological measurements of cardiac muscle function with a novel transgenic mouse model in which a modified Gicoupled receptor (Ro1) is targeted to the heart. Expression of Ro1 is regulated by a tetracycline-controlled expression system (tet-system). We have recently shown that chronic Ro1 expression causes CHF and major abnormalities of Ca2+ transients and contraction. In contrast, acute Ro1 expression causes significant protection against ischemia/reperfusion injury, suggesting a dual role for increased Gi signaling in cardioprotection and disease. For this proposal we will determine the ec-coupling mechanisms and Gi signaling mechanisms involved in CHF and cardioprotection. Using single myocytes, cardiac trabeculae, and Langendorff perfused mouse hearts, we will determine the effect of Ro1 expression on Ca2+ transients and determine the mechanisms responsible by localizing abnormalities to specific Ca2+ handling processes. We will determine the effect of Ro1 expression on Ca2+-responsiveness and determine the mechanisms responsible by localizing abnormalities to specific contractile and regulatory proteins. Using the tet-system to turn off Ro1 expression after induction of CHF, we will determine the extent to which ec-coupling abnormalities are reversible. To elucidate signaling mechanisms, we will determine which of the major Gi pathways in the heart (Gi2 and Gi3) are involved; and whether signaling via the G protein alpha subunit and/or the betagamma dimer is involved. Using 3 model systems we will investigate Gi signaling effects (both deleterious and beneficial) and the ec-couplingand signaling mechanisms involved in: Aim 1. CHF caused by Ro1 expression; and recovery after terminating Ro1 expression. Aim 2. Acute Cardioprotection caused by Ro1 expression. Aim 3. CHF caused by ischemic cardiomyopathy. This research will provide new information on the dual role of Gi signaling in both heart failure and cardioprotection which may help identify new strategies to treat heart disease. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •
Project Title: HOXA9 GENE AS A THERAPEUTIC TARGET IN LEUKEMIA Principal Investigator & Institution: Lawrence, Hugh J.; Professor of Medicine; Northern California Institute Res & Educ 4150 Clement Street (151-Nc) San Francisco, Ca 941211545 Timing: Fiscal Year 2002; Project Start 12-APR-2001; Project End 31-MAR-2004 Summary: (provided by applicant) A growing body of evidence supports the notion that misexpression of the HOXA9 homeobox gene is a common and critical event in myeloid leukemogenesis. Enforced expression of HOXA9 in murine marrow cells is clearly leukemogenic, and the gene is aberrantly upregulated in a large majority of cases of human acute myelogenous leukemia (AML). In a recent survey of 6,800 human genes in acute leukemia, HOXA9 expression was shown to be highly specific for AML and was the single best marker for a poor outcome. The major hypothesis of this grant is that aberrant activation of HOXA9 is a frequent downstream consequence of many, if not most, oncogenic events that lead to AML, and that this activation is critical to the induction and maintenance of the malignant phenotype. An additional key hypothesis is that HOXA9 overexpression contributes to the drug resistance phenotype. The focus of this application is to explore strategies to inhibit HOXA9 expression and/or function as a novel therapeutic approach for AML. This project has 3 major aims: i) to test the in
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vitra biologic effects of over-expression of HOXA9 in a factor-dependent nonleukemogenic myeloid cell line engineered to express high levels of HOXA9 in a tetracycline-regulatable manner, and to use this inducible cell line model to test strategies to block HOXA9 expression. ii) to develop an in vivo model of a Tetregulatable HOXA9-driven AML in mice, which can be used to test treatment the strategies developed in Aim #1 in a whole animal, and iii) to study the ability of antiHOXA9 strategies to alter the proliferation, differentiation and chemotherapeutic sensitivity of fresh leukemic cells from patients, and of human myeloid leukemic cell lines that show high levels of endogenous HOXA9 expression. The specific strategies to be tested include the use of conventional antisense oligonucleotides, double-stranded DNA decoys, and double-stranded RNA to induce RNA interference. We anticipate that therapies targeting the expression and/or function of HOX proteins could have a major role in the clinical treatment of leukemia. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •
Project Title: IN VIVO MODULATION OF PROGRESSION IN COLON CANCER Principal Investigator & Institution: Willson, James K.; Director, Ireland Cancer Center; Medicine; Case Western Reserve University 10900 Euclid Ave Cleveland, Oh 44106 Timing: Fiscal Year 2002; Project Start 06-SEP-1995; Project End 31-JUL-2004 Summary: (Applicant's Abstract) Employing unique cell and xenograft models, pathological alterations in growth factor responses were demonstrated to play key roles in colon cancer progression. Using a tetracycline repressible expression system in colon cancer xenograft models, loss of TGF beta signaling was linked to colon cancer progression and restoration of TGF beta signaling reversed tumorigenicity. In a second line of investigation, ectopic expression of TGF alpha resulted in accelerated tumor growth and tetracycline mediated reversal of this ectopic expression caused tumors to regress. At the inception of the studies, it was anticipated that the primary consequence of disrupted growth factor signaling in these colon cancer xenograft models would be a direct alteration in growth regulation at the cell cycle level. Unexpectedly, the results suggest that the altered tumor growth was largely due to modulation of extracellular components of the xenograft such as integrin expression or angiogenesis and that these changes in turn appear to have dramatic effects on in vivo tumor cell proliferation or apoptosis. These results suggest that tumor progression involves autocrine growth factor controlled interactions of malignant cells with the tumor microenvironment to prevent or treat colon cancers. To examine the role of candidate autocrine activities in human colon cancer progression, in vivo models which will confirm the dependency of tumor growth on these autocrine activities by modulating downstream effectors of their action are planned. Candidate molecular targets will be modulated in vivo using tetracycline controllable systems. A central issue which the applicant will examine is the relationship of tumor stage on the impact of growth factor modulation. For the purposes of these studies, he plans to evaluate xenograft tumors at two different stages, the dormant phase or pre-angiogenic phase of growth and the growth phase or post "angiogenic switch" phase. By linking the expression of a specific molecular mechanism (e.g. elevated angiogenesis due to malignant cell VEGF expression) to a tetracycline responsive promotor, he can examine the impact of modulating that mechanism in vivo at these two stages of xenograft tumor progression. The ultimate goal of this proposed investigation is to use the unique human colon cancer xenograft models that will be developed to evaluate new pharmaceutical agents designed to target novel molecular mechanisms of tumor progression. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen
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Project Title: INHIBITION OF CNV USING A TRANSGENIC PEDF MODEL Principal Investigator & Institution: Duh, Elia J.; Professor; Ophthalmology; Johns Hopkins University 3400 N Charles St Baltimore, Md 21218 Timing: Fiscal Year 2002; Project Start 01-AUG-2002; Project End 31-JUL-2005 Summary: (provided by applicant): Age-related macular degeneration (AMD) is the leading cause of blindness among the elderly in the United States. Choroidal neovascularization (CNV) is largely responsible for severe vision loss from AMD. As new and promising treatments emerge for the treatment of choroidal neovascularization, in vivo approaches will be needed not only to evaluate efficacy, but also to address issues important for clinical trials (e.g., dosing, toxicity). We thereby propose to use an inducible transgenic mouse model as an innovative approach to the study of inhibition of CNV. Specifically, we propose to study the effects of pigment epithelium-derived factor (PEDF), which has emerged as a potent inhibitor of angiogenesis, with dramatic inhibitory effects on corneal, retinal, and choroidal neovascularization. Our long-term oal is to develop PEDF as a ther~eutic modality for the prevention as well as treatment of choroidal neovascularization. We hyaothesize that PEDF can cause regression of existing choroidal neovascularization, in addition to inhibiting CNV formation. Accordingly, we propose the following Specific Aims: (1) Develop a transgenic PEDF mouse model with retina-specific, inducible expression of PEDF. Aim 1 will include the characterization of spatial, temporal, and quantitative expression of induced PEDF in the mouse model. (2) Define the potential of PEDF as a therapeutic agent for choroidal neovascularization using the laser-induced CNV model. Aim 2 will determine if transgenic PEDF expression can prevent choroidal neovascularization as well as cause regression of existing CNV. In addition, Aim 2 will address the PEDF dosage requirements required for prevention of CNV, as well as the duration of PEDF presence necessary for prevention. Finally, Aim 2 will determine if transgenic PEDF expression causes choroidal endothelial cell apoptosis in vivo. In our studies, we will adapt the tetracycline-inducible gene expression system to induce photoreceptor-specific expression of PEDF. We will study the effects of transgenic PEDF expression in mice on laser-induced choroidal neovascularization. It is anticipated that our proposal will provide a strong foundation for further studies regarding the mechanism of PEDF action. In addition, our studies will provide a new experimental approach for the study of candidate inhibitors of CNV, providing important data regarding efficacy, therapeutic dose, frequency of administration, and toxicity. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen
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Project Title: LAMININ ALPHA 1 IN LUNG DEVELOPMENT AND REPAIR Principal Investigator & Institution: Adair-Kirk, Tracy L.; Barnes-Jewish Hospital Ms 9094-212 St. Louis, Mo 63110 Timing: Fiscal Year 2002; Project Start 01-AUG-2002; Project End 31-JUL-2003 Summary: (provided by applicant): Based primarily on in vitro studies, laminin alpha1 is believed to play important roles in early lung development, yet it is not expressed in normal adult mouse or human lung. However, we recently detected laminin alpha1 expression in adult mouse lungs following bleomycin-induced lung injury. SPECIFIC AIM 1 of this proposal is to define in vivo roles for laminin alpha1 in lung development and repair. Conventional laminin alpha1 knockout mice die at E5, prior to lung bud formation. Therefore, we will develop conditional laminin alpha1 knockout mice. With these mice and a doxycycline-inducible cre/lox system, we can obtain temporal-spatial control of laminin alpha1 expression. We will use this system to regulate laminin alpha1
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expression at various stages of lung development and during bleomycin-induced lung injury. These studies will determine how the absence of laminin alpha1 affects lung development and repair. To elucidate the mechanisms by which laminins play roles in alveolar re-epithelialization following diffuse alveolar damage, SPECIFIC AIM 2 will focus on the roles of laminins-1 and -10 in epithelial cell proliferation, migration, and differentiation. Better understanding of the role of BM components like laminins in lung development and repair will enhance the ability to promote restoration of lung structure and function after diffuse alveolar damage. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •
Project Title: MECHANISMS OF EPITHELIAL ALTERATIONS IN DIABETIC CORNEA Principal Investigator & Institution: Ljubimov, Alexander V.; Director; Cedars-Sinai Medical Center Box 48750, 8700 Beverly Blvd Los Angeles, Ca 900481804 Timing: Fiscal Year 2002; Project Start 01-AUG-2001; Project End 31-JUL-2005 Summary: (provided by applicant): Diabetic retinopathy has been the leading cause of blindness in the United States since 1974. It is manifest by progressive changes in the microvasculature of the diabetic eye, leading to intravitreal hemorrhages, retinal edema, neovascularization, and detachments. Along with the retina, cornea, lens and iris are also affected by diabetes. Many diabetics suffer from diabetic keratopathy that includes recurrent erosions, epithelial fragility, abnormal wound healing and increased susceptibility to injury. Altered epithelial-stromal interactions and epithelial basement membrane (BM) defects likely contribute to diabetic keratopathy. Despite clinical importance of diabetic corneal disease, the molecular mechanisms of this complication are not understood. In our preliminary studies, the expression of many BM components and proteinases has been analyzed in normal and diabetic human corneas. We show that: 1. Diabetic retinopathy (DR) corneas have severely decreased epithelial BM immunostaining for laminin-1, laminin-10, nidogen-1/entactin, and for epithelial integrin alpha3 beta1; 2. Gene expression of BM proteins and integrin alpha3 beta1 is not changed in diabetic and DR corneal epithelium; 3. Gene and protein expression of matrix metalloproteinase (MMP)-10 increases in diabetic and DR corneal epithelium and stroma, and MMP-3 expression increases in diabetic and DR corneal stroma. The data suggest that major components of corneal epithelial BM are altered in diabetes and especially DR due to elevated activity of specific proteinases, e.g., of MMP-1O that is expressed in the epithelium. Our hypothesis is that corneal epithelial BM in diabetes and DR undergoes degradation by elevated proteinases, notably by MMP-10. Proteinase expression and activity may be stimulated by specific growth factors activated by diabetic microenvironment. These alterations may constitute the molecular mechanism of corneal epithelial abnormalities in diabetes. Specific Aim 1.To characterize the effect of MMP-10 on the integrity of corneal epithelial BM and integrin alpha3 beta1 and on wound healing in organ-cultured human corneas. Specific Aim 2. To identify by gene array analysis growth factors and cytokines abnormally expressed in diabetic and DR corneas and examine their effects on MMP-10 and wound healing in normal organcultured corneas. Specific Aim 3. To assess by gene array analysis the expression levels of various proteinases in diabetic, DR and normal human corneas. Identify and analyze additional proteinases with elevated expression in diabetic corneas. Specific Aim 4. To attempt blocking BM and integrin degradation in human diabetic and DR organ-culture corneas. Neutralizing antibodies to specific growth factors and proteinases (primarily, MMP-10), and various MMP inhibitors including clinically approved tetracyclines will
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be tested in organ-cultured corneas. These studies could lead to the development of novel therapeutics that would block the progression of diabetic keratopathy. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •
Project Title: MECHANISMS OF TRANSCRIPTIONAL REGULATION Principal Investigator & Institution: Manley, James L.; Professor and Chairman; Biological Sciences; Columbia Univ New York Morningside 1210 Amsterdam Ave, Mc 2205 New York, Ny 10027 Timing: Fiscal Year 2002; Project Start 01-APR-1987; Project End 31-MAR-2003 Summary: The experiments described in this project are designed to provide insights into some of the detailed molecular mechanisms involved in regulation of transcription in metazoan cells. They all combine biochemical and genetic approaches to address specific outstanding issues in the field. The following specific aims are proposed. 1. Activation. Two cell lines, which will allow genetic analyses of the TFIIK components TBP and TAFII32, will be constructed and studied. The experiments will utilize the chicken cell line DT40, and employ a technology developed previously in which the endogenous alleles of each gene will be disrupted in the presence of tetracycline (tet)repressible transgene encoding the appropriate protein. How in vivo depletion influences cell growth and (presumably) brings about cell death will be determined. The effects of depletion on transcription, generally and of specific genes, will be measured, and the basis of any gene-specific effects investigated. The consequences of depletion on TFIID structure and on accumulation of other general transcription factors will be determined. A genetic complementation assay will be used to study the species specificity of these factors, as well as the requirement and role of specific protein domains (such as the N terminus of TBP) in the various functions of the proteins. 2. Repression. Studies to elucidate the mechanism employed by the Drosophila repressor Even- skipped (Eve) will be continued. Efforts will be made to prepare large amounts of a minimal, active Eve derivative in a concentrated form so that the Eve-TBP complex can be reconstituted and crystalized and its structure determined by X-ray diffraction. Selected mutations in TBP will be examined for their effects on Eve binding, and transcriptionally active TBP mutants compromised in Eve binding will be used to reconstitute in vitro transcription and the ability of Eve to repress transcription determined. The recently discovered inhibitory effect of phosphorylation on Eve repression activity and TBP binding will be investigated further. The sites of phosphorylation by GSK-3/Shaggy and casein kinase II will be mapped and mutated and the effects of the mutations determined. The mechanism by which the phosphorylated inhibitory domain functions will be investigated. 3. Regulation of Dorsal. Studies on the activities and interactions of three genetically- defined factors, Toll, Tube and Pelle, that function to activate the intracytoplasmic Dorsal signaling cascade in Drosophila will be continued. The unexpected ability of Tube to function in the nucleus will be pursued using in vitro assays, and the requirement for Pellecatalyzed phosphorylation of the Tube death domain investigated. The mechanism by which Pelle autophosphorylation is regulated will be investigated, and the hypothesis that Pelle autophosphorylation is controled in the early embryo will be tested. Phosphorylation-dependent interactions involving the intracytoplasmic domain of the Toll receptor and Pelle will be studied to determine how Toll modulates Pelle kinase activity. Pelle phosphorylation sites in Pelle itself and Tube, as well as newly described site(s) in the Toll I1-1R homology region, will be mapped and the effects of mutations in functional assays determined. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen
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Project Title: MICROENVIRONMENTAL CONTROL OF THE RADIATION RESPONSE Principal Investigator & Institution: Dicker, Adam P.; Associate Professor & Director of Experi; Radiation Oncology; Thomas Jefferson University Office of Research Administration Philadelphia, Pa 191075587 Timing: Fiscal Year 2004; Project Start 01-APR-2004; Project End 31-MAR-2008 Summary: (provided by applicant): The success or failure of radiation therapy rests, in part, on selective killing of tumor cells over normal cells. It is poorly known which molecular mechanisms are responsible for this difference. The applicants will test the overall hypothesis that adhesion to physiological extracellular matrices provides positional survival signals to epithelial normal cells that are reduced or absent in tumor cells. It is further hypothesized that tumor cells counteract loss of matrix-dependent survival signals through inappropriate activation of growth factor receptors. In support of these hypotheses, preliminary evidence revealed that certain matrix components, including the basement membrane type IV collagen, enhance radioresistance of malignant keratinocytes when the epidermal growth factor receptor (EGFR) is blocked. The overall goal of this application is to further define molecular mechanisms and pathways by which integrin engagement and EGFR activation coordinately control epithelial cell survival. This will be done using normal keratinocytes and cells representing an early stage of keratinocyte tumor progression (HaCaT). The Specific Aims of the work proposed are to (1) define matrix components and cognate matrix adhesion receptors that contribute to radiation resistance in these cells, (2) characterize coordinate control of signaling pathways (PI-3- kinase/AKT; MEK/MAPK) that contribute to cell survival by integrin engagement and EGFR activation, (3) assess functional roles of integrins and the EGFR in survival of HaCaT cells grown as tumor cell nests in organotypic epidermal reconstructs. Epidermal reconstructs represent a uniquely versatile three-dimensional tissue model to assess complex regulation of cell survival. To assess functional roles of specific surface receptors and signaling molecules in HaCaT cell survival the investigators have established a tetracycline regulatable gene expression system in these cells allowing the conditional expression of antisense and dominant negative constructs even if they are lethal in 2D cell culture. The use of these tools in organotypic reconstructs promises to provide novel information about cell survival signaling in an 'in vivo' context with clear implications for therapeutic intervention. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen
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Project Title: MMP REGULATION BY DOXYCYCLINE IN AORTIC ANEURYSM Principal Investigator & Institution: Baxter, B Timothy.; Professor of Surgery; Surgery; University of Nebraska Medical Center Omaha, Ne 681987835 Timing: Fiscal Year 2002; Project Start 01-FEB-2000; Project End 31-JAN-2005 Summary: Abdominal Aortic Aneurysm (AAA) is a common and devastating disease which is increasing in incidence. Although easy and inexpensive to detect by ultrasound, most aneurysms are small when detected and there is currently no medical regimen which will inhibit their growth. There is an increasing body of evidence implicating a family of matrix degrading enzymes, the matrix metalloproteinases (MMPs) in AAA. Although both MMP-9 and MMP-12 may have a role in AAA, we have identified a significant increase in total MMP-2 in AAA. Importantly, a larger proportion of the MMP-2 in AAA tissue is in the active form and is directly bound to the matrix suggesting ongoing proteolysis. In addition, we have demonstrated that AAA tissue
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contains increased levels of membrane type 1 MMP, the activator of MMP-2. We have also shown that doxycycline inhibits MMP-2 production by aortic smooth muscle cells in culture. We hypothesize that MMP-2, through its increased activation, has a central role in aneurysm formation and that this could be inhibited by doxycycline. This hypothesis will be examined through the following specific aims: 1. Determine the effects of individual MMPs implicated in AAA including MMP-2, MT1-MMP, MMP-9 and MMP-12 on the size and rate of aneurysm formation in a murine AAA model. 2. Determine the effects of doxycycline on the size and rate of aneurysm formation and progression in a murine model and correlate these effects with serum doxycycline levels. 3. Determine the mechanisms by which doxycycline down regulates MMPs in human aortic smooth muscle cells. Specific aim 1 will be accomplished using a mouse model of AAA characterized in our laboratory with four different knock-out mice, including MMP-2, MMP-9, MMP-12 and a TIMP-2 knock-out mouse in which activation of MMP-2 does not occur. Specific aim 2 will be accomplished by using doxycycline treatment in our murine model of AAA and correlating effects on aortic MMP expression, aneurysm size and growth rate with serum doxycycline concentrations. Specific aim 3 will be accomplished by determining MMP- 2 mRNA levels, mRNA half life, rate of mRNA transcription and identifying the doxycycline responsive elements in the MMP-2 promotor. The long term goal of this work is to develop pharmacologic therapies which specifically target MMPs important in aneurysm pathogenesis and progression. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •
Project Title: MODIFIED LATE INFARCT REPERFUSION TO PREVENT POST MI CHF Principal Investigator & Institution: Gorman, Robert C.; Assistant Professor; Surgery; University of Pennsylvania 3451 Walnut Street Philadelphia, Pa 19104 Timing: Fiscal Year 2003; Project Start 15-APR-2003; Project End 31-MAR-2007 Summary: (provided by applicant): Congestive heart failure (CHF) has reached epidemic proportions in the United States. The significant majority of these cases are the result of postinfarction LV remodeling. It is now established that early infarct expansion initiates an inexorable myopathic process in normally perfused myocardium that leads to a CHF. Infarct stiffening can prevent adverse remodeling and reperfusion therapy is currently the best available means to accomplish this. However, reperfusion therapy often fails to influence remodeling especially after long ischemic intervals. Much has been learned about pathophysiology and pathology of myocardial ischemia/reperfusion (I/R) but a comprehensive understanding of this very complex phenomenon has been illusive. It is not the central focus of this proposal to explore the mechanism of myocardial reperfusion injury (although the apoptosis studies will provide new information on how this unique form of cell death contributes to I/R injury) but rather to exploit what is already known to improve the results of reperfusion therapy for acute myocardial infarction. Our hypothesis is that even very limited myocardial salvage (too small to improve contractile function) within the area at risk can alter infarct material properties enough to prevent early infarct expansion, stabilize postinfarction ventricular geometry and prevent the development of CHF. A well-established sheep model of postinfarction ventricular remodeling and progressive CHF will be used. The effect of unmodified and modified reperfusion after varying ischemic intervals on infarct expansion and the outcome of remodeling will be assessed using the imaging techniques of sonomicrometry array localization and quantitative echocardiography. Myocytes are lost at the time of reperfusion due to necrosis, apoptosis and/or microvascular no
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reflow. Adenosine, abciximab and minocycline have been selected to modify the infarct reperfusate because they have been demonstrated in clinical and/or experimental studies and confirmed in the sheep model to limit infarct size within in the area at risk by affecting one or more of the mechanisms of cell loss that occur during myocardial ischemia/reperfusion. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •
Project Title: MODULATION OF LOCAL BONE TISSUE MATERIAL PROPERTIES Principal Investigator & Institution: Les, Clifford M.; Bone and Joint Center; Case Western Reserve Univ-Henry Ford Hsc Research Administraion Cfp-046 Detroit, Mi 48202 Timing: Fiscal Year 2002; Project Start 01-AUG-2001; Project End 31-MAY-2005 Summary: (provided by applicant): Compact bone mineral density is distributed nonuniformly within the normal bone structure. This is reflected in local variation in mechanical properties (strength and stiffness) that we believe helps to limit bending to those planes where muscles and ligaments have maximal mechanical influence. Challenges to normal bone mineral metabolism may affect this material distribution, and have structural effects disproportionate to the overall mineral loss. For instance, in postmenopausal osteoporosis, there is increased turnover of bone, and a generalized loss of bone mass, but this fully explains neither the strong association with fracture incidence, nor the substantial overlap between unaffected and fracture patients in most clinical screening measures of bone quality. Given the pre-existing material heterogeneity, any change in material properties, be it random, uniform, or systematic, is likely to have significant effects on the mechanical behavior of the structure. Therefore, therapeutic interventions designed to simply affect an overall increase in bone mass without considering regional mechanical property variation may be ineffective in preventing fracture. In compact bone, an increase in bone turnover may be seen as a branching problem in angiogenesis: new osteons, and their blood vessels, must arise from pre-existing osteons and blood vessels. If estrogen depletion were associated with a global increase in vascular and osteonal branching, the major early effects of remodeling would be seen in regions with high concentrations of pre-existing osteons. Such a scenario would produce an immediate systematic change in regional bone density that would be related not to original density, but to pre-existing remodeling patterns. Furthermore, we hypothesize that the new bone that is laid down in the estrogen-depleted condition is less densely populated by osteocytes than in the intact animal. If changes in osteocyte density were associated with alterations in the final mineralization of new bone, a more permanent change in the distribution of material properties would then ensue. We will test these hypotheses using the ovariectomizedsheep model of estrogen depletion. The radius/ulna will be tested for structural damping, stiffness, and strength before sectioning into regions for materials testing and histology. Remodeling activity will be quantified by dynamic and static histomorphometry, and by analysis of osteonal density patterns. Finally, local osteocyte population densities will be determined and compared with osteonal mineral measurements, and with mineral-independent measurements of local tissue age. In this way, we will address the issue of compact bone material heterogeneity in postmenopausal osteoporosis at the structural, materials, cell population, and biochemical levels. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen
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Project Title: MOLECULAR DISSECTION OF REACTIVE ASTROCYTE BIOLOGY Principal Investigator & Institution: Sofroniew, Michael V.; Professor; Neurobiology; University of California Los Angeles 10920 Wilshire Blvd., Suite 1200 Los Angeles, Ca 90024 Timing: Fiscal Year 2002; Project Start 01-JUL-2002; Project End 31-MAY-2004 Summary: (provided by applicant): Our long-term objective is to understand and counteract mechanisms that lead to cellular degeneration and impede axon regeneration after brain and spinal cord injury. Our specific aims here are to generate new and innovative models to study the roles played by specific molecules that are expressed by reactive astrocytes, a principal cell type in the local tissue response to injury and disease in the central nervous system (CNS). These models will help to identify key molecules that determine the biology and function of reactive astrocytes. Numerous effector molecules produced by reactive astrocytes have been described, but the roles played by these cells are not well defined. Little mechanistic information is available about how the different functions of reactive astrocytes are triggered and implemented through specific molecules. We previously developed a model for the ablation of reactive astrocytes in transgenic mice and showed that these cells are essential for local neuroprotection, blood brat barrier repair and regulation of inflammation after CNS injury. Our next goal is to identify molecular mechanisms for these phenotypes. Here, we propose to develop transgenic models for the targeted and regulatable ablation of specific molecules molecules expressed by reactive astrocytes. These models use the Cre/loxP system, where bacterial Cre recombinase I excises DNA sequences between loxP sites inserted into genes targeted for inactivation. Aim I is to generate and characterize transgenic mice that express Cre from the glial fibrillary protein (GFAP) promoter, thus targeting Cre to reactive astrocytes. Aim 2 is to generate transgenic mice in which an additional level of regulation is achieved by using a tetracycline regulatable promoter system. In these mice, Cre expression in astrocytes will be suppressed during development and activated in adult mice. Transgenic lines will be validated for use by demonstrating the specificity of the targeting of Cre activity to reactive astrocytes at the single cell level. Aim 3 is to demonstrate proof of principle by ablating a crucial regulatory molecule specifically from GFAP expressing astrocytes. STAT3 is an intracellular signal transducer of the JAK-STAT family involved in mediating the proliferation and differentiation responses to various cytokines and growth factors in may cell types. STAT3 signaling has been implicated in both astrocyte development and reactive astrocytosis. Mice with loxP sites inserted into the STAT3 gene are available and will be crossbred with Cre mice from Aims 1 and 2. STAT3-deficient astrocytes will be evaluated in vitro and after experimental CNS injury in vivo for their ability to become reactive. The consequences of the predicted failure of astrocytosis after CNS injury in mutant mice will be studied in vivo. The models from Aims 1 and 2 will allow the testing of many hypotheses about the roles that specific molecules expressed by reactive astrocytes play in the biology and function of reactive astrocytes after CNS injury. These models will be useful for many different future studies in our own and collaborating laboratories. Aim 3 will begin this process. The findings obtained in both the short and long term will contribute fundamental information about cellular and molecular mechanisms that determine functional outcome after CNS injury. Mechanistic information of this kind is essential for the development of rationally based therapeutic strategies. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen
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Project Title: MOLECULAR MECHANISMS FOR GP160-ENHANCED APOPTOSIS Principal Investigator & Institution: Mcdonald, Jay M.; Professor and Chair; Pathology; University of Alabama at Birmingham Uab Station Birmingham, Al 35294 Timing: Fiscal Year 2002; Project Start 01-APR-2001; Project End 31-MAR-2005 Summary: AIDS is characterized by, progressive loss of T cells with ultimate immune paralysis. Despite aggressive antiviral therapy, HIV-1 is not eradicated. A better understanding of HIV-1/host cell interactions is critical for identifying new possible points for therapeutic intervention. Apoptosis, programmed cell death, represents one possible pathway for HIV-1-mediated loss of T cells and other cells in AIDS. Transfection of the HIV-1 coat glycoprotein, gp160, into T cell lines enhances Fasmediated apoptosis by a mechanism that involves increased calmodulin expression and calmodulin binding to a specific C-terminal intracellular sequence of gp41. Calmodulin antagonists inhibit gp160-enhanced Fas- mediated apoptosis and spontaneous apoptosis of CD4 cells obtained from AIDS patients. The underlying molecular mechanism for gp160 enhanced Fas-mediated apoptosis will be elucidated first using two new reagent Jurkat cell lines, with stably expressing gp160, and gp160 with an A->W mutation at 835 that eliminates calmodulin binding under tetracycline-off control. Furthermore, these experiments will be placed in the context of HIV-1 and AIDS by investigating Fasmediated apoptosis in gp160 variants from primary HIV-1 isolates and infectious virus with several point mutations of gp160 including A835W that have impaired calmodulin binding. Acute and chronic infection of T-cell lines and infection of primary lymphocytes with these reagents are incorporated as part of this comprehensive program that is investigating the key calmodulin- dependent signal transduction events in AIDS pathogenesis. The Specific Aims are: I. Characterize the effects of gp160 and calmodulin-binding deficient mutants, including gp160A835W, on Fas-mediated apoptosis and Ca=2+/calmodulin related signaling. II. Characterize Fas-mediated apoptosis and viral replication using gp160's from primary HIV-1 isolates with variations in the calmodulin- binding domain and using infectious virus with selected calmodulin- binding deficient gp160 mutations, including gp160A835W. III. Characterize the molecular mechanisms regulating calmodulin expression in 160 expressing cells. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen
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Project Title: MOLECULAR MODELS OF IMMUNE-MEDIATED VASCULAR INJURY Principal Investigator & Institution: Bender, Jeffrey R.; Professor and Associate Chief; Internal Medicine; Yale University 47 College Street, Suite 203 New Haven, Ct 065208047 Timing: Fiscal Year 2002; Project Start 01-APR-1991; Project End 31-MAY-2007 Summary: (provided by applicant) Adhesion receptor-ligand interactions can influence vascularized organ allografts at multiple levels, including targeted trafficking of host leukocytes into the graft, costimulation of alloreactive T cells through leukocyte integrins, or directed killing of donor target cells by conjugate formation with cytotoxic, allospecific effector cells. We have previously demonstrated that LFA-1 (al B2) plays a critical role in lymphocyte-EC adhesion and lymphocyte migration, is dynamically regulated and, as a transmembrane signaling molecule, stabilizes Thi cytokine transcripts including IFN-g, TNF-a, and LL-2. This RNA stabilization is, in part, cytoskeleton dependent, is directed at modulation of transcript degradation through AU-rich target sequences, and requires the LFA-1 engagement-induced nuclear-to-
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cytoplasmic translocation of the critical RNA binding protein HuR. This has led to our overall hypothesis as follows: T cell co-activation, through LFA-1, drives actin cytoskeleton dependent modulation of HuR which, in turn, facilitates stabilization of labile T cell activation transcripts for multiple pro-inflammatory and pro-proliferative key effector molecules in acute and chronic vascular rejection. Specific proposals now include to (1) define proximal signaling components of LFA-1-mediated HuR translocation, by using actin cytoskeleton-disrupting agents and rho family GTPase mutants in T cell or LFA-1+ stable transfectant HuR translocation assays; (2) assess LFA1-induced biochemical modifications on, and induced protein-protein interactions with, HuR in I cells, using phosphopeptide mapping and coimmunoprecipitation proteomics; (3) evaluate the effect of LFA-1 engagement on ARE-bearing transcripts encoding cell cycle regulatory molecules, including G1-, S- and G2-specific cyclins; and (4) test the role of HuR function in heterotopic and aortic allograft models in vivo with a T cell-specific, tetracycline regulable HuR knock out mouse. This work may provide insight into cellular and molecular triggers of allograft rejection, including those directed at the vasculature, and immune activation more broadly. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •
Project Title: MOLECULAR PATHOGENESIS OF CARDIAC DYSFUNCTION Principal Investigator & Institution: Giroir, Brett P.; Associate Professor; Pediatrics; University of Texas Sw Med Ctr/Dallas Dallas, Tx 753909105 Timing: Fiscal Year 2002; Project Start 01-APR-2000; Project End 31-MAR-2004 Summary: The goal of this proposal is to determine the molecular mechanisms of cardiac dysfunction that occurs during septic shock and following thermal trauma. Previous work has demonstrated that cardiac dysfunction is mediated by the cytokine tumor necrosis factor-alpha (TNF), which is produced locally in the myocardium by cardiac myocytes. This proposal utilizes novel molecular and genetic strategies to investigate the mechanisms of TNF's detrimental effects and to develop therapeutic approaches for TNF-related cardiac contributions. First, we will study transgenic mice in which TNF is constitutively expressed only by cardiac myocytes. These mice develop profound cardiac dysfunction, cardiomyopathy, myocarditis, and cardiac failure which mimics cardiac contractile dysfunction in humans. By breeding these transgenic animals to mice which have undergone targeted disruption of iNOS (inducible nitric oxide synthase), IRAK (IL-1 receptor associated kinase), and ICAM-1 / P-selectin, as well as by pharmacological inhibition of specific pathways, we will quantitatively determine the involvement of iNOS, IL-1, and transmigrated leukocytes in the pathogenesis of myocardial failure. Cardiac phenotype will be characterized primarily by in vitro Langendorff perfusion of isolated mouse hearts; confirmatory longitudinal analysis of function will be accomplished in vivo by ECG-gated MRI imaging. Physiologic findings will be correlated with survival, post-mortem histology, and the pattern of cardiac gene expression. Next, we will optimize the transgenic animal model by developing a binary transgene system which is cardiac specific, and regulatable by dietary tetracycline. Through this system, we will determine if the effects of TNF are related to dose and duration of expression. We will describe the cascade of secondary cytokines induced by TNF. We will also determine whether low-level, transient expression of TNF may be evolutionary adaptive, and serve a protective role against subsequent cardiac insults. By understanding the molecular mechanisms by which TNF impedes myocardial performance, it will be possible to develop specific, targeted therapeutic strategies for the treatment of sepsis, burn trauma, and other TNF-related cardiac conditions such as cardiomyopathy, myocarditis, and ischemic heart disease.
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Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •
Project Title: MOLECULAR TARGETS IN PEPTIDOGLYCAN SYNTHESIS Principal Investigator & Institution: Davies, Christopher; Assistant Professor; Biochem and Molecular Biology; Medical University of South Carolina 171 Ashley Ave Charleston, Sc 29425 Timing: Fiscal Year 2003; Project Start 01-FEB-2003; Project End 31-JAN-2007 Summary: (provided by applicant): The murein sacculus is a mesh of cross-linked peptidoglycan strands that confers rigidity to the bacterial cell wall. Beta-lactam antibiotics, which target the essential transpeptidases (penicillin-binding proteins or PBPs) that cross-link the peptidoglycan strands, are important compounds in the treatment of bacterial diseases. Unfortunately, the emergence of multiple mechanisms of antibiotic resistance threatens to make these and other antibiotics obsolete in the treatment of bacterial infections. Along with other pathogenic bacteria, antibiotic resistance in Neisseria gonorrhoeae is a growing problem. Penicillin and tetracycline, once the antibiotics of choice for treatment of gonococcal infections, are no longer be used due to the emergence of resistant strains. Moreover, increasing numbers of strains are now resistant to the fluoroquinolones, one of the two antibiotics current recommended in the treatment of gonorrhea. Clearly there is an urgent need to develop new antimicrobials directed both against well-known molecular targets, such as PBPs, but also against novel targets. In this proposal we describe structural and biochemical studies of three enzymes involved in peptidoglycan metabolism: a D-Dcarboxypeptidase from E. coli (PBP 5) that serves as a model system for elucidating PBP function, an essential transpeptidase (PBP 2) from N. gonorrhoeae that is the lethal target of current beta-lactam antibiotics, and a lytic transglycosylase, MltA, also from N. gonorrhoeae, that serves as the lynchpin of the cell wall synthesizing complex. Each of these proteins has been selected to address one or more of the following aims: (a) to understand the biology of peptidoglycan synthesis, (b) to explore their interactions with antibiotics, (c) to elucidate the molecular basis for antibiotic resistance and (d) to examine their potential as targets for drug development. Studies on PBP 5 will elucidate the mechanism by which this enzyme hydrolyzes substrate and will provide a better understanding of PBP-antibiotic interactions in general. The molecular basis for antibiotic resistance in PBP 2 will be investigated by structural studies of the native enzyme and of a mutant isolated from a penicillin-resistant strain. The role of MltA as part of a multienzyme complex mediating peptidoglycan synthesis as well as its suitability as a novel target for antimicrobials will be examined by solving its crystal structure. These studies will provide a framework for future studies aimed at structurebased drug design and will provide substantial insight into the mechanisms of peptidoglycan synthesis. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen
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Project Title: MOUSE CANCER MODELS BY REGULATED INACTIVATION OF TUMOR S Principal Investigator & Institution: Lee, Eva Y.; Chancellor Professor; Developmental and Cell Biology; University of California Irvine Irvine, Ca 926977600 Timing: Fiscal Year 2002; Project Start 30-SEP-1999; Project End 31-MAR-2004 Summary: Studies in the last two decades have provided a significant new insights into human cancer. Mutations of the retinoblastoma gene (RB) and p53 are involved in about 70 percent of human cancer. These genes, as well as two other tumor suppressor genes,
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BRCA1 and BRCA2, that are mutated in families predisposed to breast cancer, appear to be also implicated in prostate cancer. We are interested to develop mouse mammary and prostate models of tumorigenesis with an etiology and pathogenesis similar to humans. Due to embryonic lethality and the development of a prevalent type of lethal tumor in young mice, previous models with the above four genes were restricted in their use for cancer research. To circumvent these limitations, we show in this application that the temporal, spatial, and cell-type-specific inactivation of tumor suppressor genes can be achieved in mice using a novel method that places expression of the Cre-loxP recombinase under the regulation of the tetracycline binary system of gene control. This approach has been applied to generate mouse cancer models by conditional inactivation of Rb, p53, Brca1, and Brca2. These mice will be used to: (A) test the specificity of a given tumor suppressor singly or in combination in tumor formation, and to validate the similarity of their tumors to human cancer by pathological and molecular analyses. (B) evaluate the sensitivity of magnetic resonance image analysis for early detection of cancer. (C) investigate environmental factors, such as low dose radiation in tumor formation. (D) test hormone treatments or caloric restriction in preventing tumor formation. (E) evaluate the efficacy of anti-cancer drugs and targeted therapy using tumor suppressor genes in the treatment of breast and prostate cancer in mice. To achieve this goal, four overall specific aims are proposed as follows: (1) To generate mice with tumor suppressor genes, including p53, Rb, Brca1 and Brca2, whose critical exon(s) have integrated flanking loxP (floxed) sites. (2) To establish transgenic mice that demonstrate temporal, spatial and cell-type- specific DNA excision by regulating the expression of the Cre- recombinase with the tetracycline binary system for gene control. (3) To cross mice in Aims 1 and 2 to produce the desired transgenic/floxed mice. (4) To characterize breast and prostate tumor formation and progression in these mice under a variety of settings where tumor suppressor genes, either singly or in combination, are inactivated. In collaboration with other members of the consortium, the involvement of these tumor suppressor genes in other types of cancer could be investigated. In addition, the transgenic mice with regulated Crerecombinase, either ubiquitously or cell-type- specifically expressed, would be available to other investigators in the consortium to cross with their floxed mice to greatly expand the repertoire of site-specific knock-outs. These valuable mouse models will be extremely useful for the general community of cancer researchers. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •
Project Title: MOUSE MODELS TO STUDY GONADAL TUMOR DEVELOPMENT Principal Investigator & Institution: Matzuk, Martin; Professor; Pathology; Baylor College of Medicine 1 Baylor Plaza Houston, Tx 77030 Timing: Fiscal Year 2002; Project Start 01-AUG-1993; Project End 31-MAR-2006 Summary: Cancer is a major cause of morbidity and mortality in our society. Like other malignancies, ovarian and testicular cancers arise through multiple genetic alterations. Using a knockout mouse model, we discovered that the inhibins, alpha:beta heterodimeric members of the transforming growth factor beta superfamily, are tumor suppressors with specificity for the gonads and adrenal cortex. In mice lacking alpha inhibin, neither inhibin A (alpha:betaA) nor inhibin B (alpha:betaB) is produced, and granulosa/Sertoli cell tumors of the ovaries and testis develop as early as 4 weeks of age with 100% penetrance. The ovarian tumors are often mixed tumors consisting of both granulosa cell and Sertoli cell components. Castration of male and female inhibin a knockout mice leads to a high incidence of sex steroidogenic adrenal cortical tumors (66 of 67 mice). Mice with gonadal or adrenal tumors are rapidly affected by a cancer
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wasting syndrome which mimics the cachexia syndromes associated with human cancer cases. Using a genetic approach to generate double mutant mice lacking both alpha inhibin and activin receptor type IIA (ActRIIA), we showed that tumor-produced activin directly signals through ActRIIA in the liver and stomach to cause this wasting syndrome. Using similar genetic approaches, we have shown the following: (1) Overexpression of the activin antagonist follistatin alleviates some of the cachexia-like symptoms caused by the circulating activins and slows the tumor development; (2) Absence of gonadotropins FSH and LH, prevents tumor development; (3) Lack of only FSH slows tumor development in both sexes, but mortality rates are sexually dimorphic (0% survival of females, 70% survival of males) demonstrating that FSH functions differentially in ovarian and testicular tumorigenesis; and (4) Absence of the cyclindependent kinase (Cdk) inhibitor p27(Kip1) speeds the process of gonadal tumorigenesis. The studies in this competitive renewal proposal will continue to define the inhibin signaling process and the mechanism of inhibin action in gonadal and adrenal function in vivo. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •
Project Title: MYC'S ROLE IN THE INITIATION AND MAINTENANCE OF CANCER Principal Investigator & Institution: Felsher, Dean W.; Medicine; Stanford University Stanford, Ca 94305 Timing: Fiscal Year 2002; Project Start 01-JUN-2001; Project End 31-MAY-2006 Summary: (provided by applicant) The targeted repair or inactivation of damaged proto-oncogenes (oncogenes) may be a specific and effective treatment for neoplasia. My long-term goal is to understand bow oncogenes induce and maintain tumorigenesis. My strategy has been to generate a conditional transgenic model system using the tetracycline regulatory system to investigate how oncogene activation causes tumorigenesis and when continued activation is required to maintain a tumorigenic phenotype. I have focused on investigating how over-expression of the MYC protooncogene causes tumorigenesis. My hypothesis is that the mechanism by which MYC induces tumorigenesis will define when its continued expression is required to maintain a tumorigenic phenotype, and thus, when its inactivation will induce tumor regression. Recently I have shown that MYC-induced tumors regressed upon MYC inactivation (see Appendix, Feisher and Bishop, Molecular Cell, 1999). From these results, I conclude that there are circumstances when the inactivation of MYC can cause tumor regression. Now, I propose experiments to address the following three specific aims:(1) 1 will determine how MYC activation induces tumorigenesis in hematopoietic cells by influencing the cell cycle, genomic stability and apoptosis and how other oncogenes (p53-I-, p]9ARF-/-, ROAS, BCL2) cooperate with MYC to influence these same parameters. (2) I will determine how MYC inactivation causes tumor regression, if MYC re-activation permits tumor relapse, and if cooperating oncogenic events (p53-I-, p19ARF-/-, RAS, BCL2 ) prevent regression or promote relapse. (3) I will determine how MYC maintains a tumorigenic phenotype by examining if (MYC family members (N-, L-MYC), S-MYC or MYC mutants defective for specific functional domains or MYC 's transcriptional targets (ODC, eIF-4E, TERT) can functionally replace MYC. I will attempt to identify novel genes that can functionally replace MYC to maintain in part or whole its neoplastic phenotype. The results obtained from these studies will be useful in determining how MYC causes tumorigenesis and defining when the inactivation of MYC is likely to be effective in the treatment of human neoplasia. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen
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Project Title: NAIVE T CELL SURVIVAL: TCR AND IL-7R SIGNAL INTERPLAY Principal Investigator & Institution: Benoist, Christophe O.; Section Head; Joslin Diabetes Center Boston, Ma 02215 Timing: Fiscal Year 2002; Project Start 01-APR-2002; Project End 31-MAR-2007 Summary: The population dynamics of T lymphocytes is an increasingly topical issue because of its important medical ramifications. An individual's pool of T cells is homeostatically regulated, integrating cell input, proliferation and death to maintain a remarkably constant total count. The focus of this proposal is maintenance of the naive T cell compartment, in particular the roles of T cell receptor (TCR) engagement of major histocompatibility complex (MHC) molecules and interleukin (IL)-7 receptor (R) binding of IL-7, both known to be required for na ve T cells to persist for prolonged periods in the peripheral lymphoid organs. Performant systems permitting T cell-specific, tetracycline (tet)-regulatable expression of TCR and MHC class II molecules in mouso already exist, as does a protocol for monoclonal antibody blockade of IL-7R. These will be employed to 1) evaluate the interplay between TCR and IL-7R- mediated survival signals at the cellular level and 2) evaluate the interplay between TCR- and IL-7R-mediated survival signals at the molecular level. In addition, a novel system will be engineered in order to 3) generate, characterize and utilize mice expressing IL-7R on T cells in a tet-regulatable fashion. Specific hypotheses that will be addressed include the notion that the signaling pathways emanating from the TCR and IL-7R intersect and the speculation that IL-7R acts as a homeostatic sensor for the naive T cell compartment. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen
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Project Title: NEK1 PROTEIN KINASE AND POLYCYSTIC KIDNEY DISEASE Principal Investigator & Institution: Chen, Yumay; University of Texas Hlth Sci Ctr San Ant 7703 Floyd Curl Dr San Antonio, Tx 78229 Timing: Fiscal Year 2003; Project Start 01-APR-2003; Project End 31-MAR-2008 Summary: Polycystic kidney disease (PKD) is the most common inherited disorder leading to chronic renal failure. Human pedigrees and several mouse models have led to cloning of genes linked to PKD. Characterization of two mice strains, kat and kat2J, both of which develop progressive PKD, has identified Nek1 (Aspergillus NIMA-related kinase 1) as a candidate protein involved in PKD. The mutations found in both kat and kat2J mice result in truncated Nekl without any coiled-coil domain at its carboxyl terminus. To date, little is known about Nekl other than its mRNA expression pattern in mice. In this proposal, Nek1 and its gene product will be characterized at molecular and cellular levels, and the potential role of Nek1 in PKD pathogenesis will be explored. In aim 1, the protein encoded by Nek1 will be characterized for its cell cycle-dependent expression pattern, kinase activity, subcellular localization, and role in kidney development. For this aim, cell and organ culture systems will be used to explore the consequences of wild type and mutant Nek1 expression via tetracycline-regulated and adenoviral vectors. Kidney tissue sections and individual cells will also be examined by immunohistochemistry. A dominant negative Nek1 mutant will be identified and used to examine its effect on kidney development in an organ culture system. In aim 2, a mouse strain in which Nek1 is specifically inactivated by gene targeting will be generated. Using the IRESbeta-geo as selection cassette, the expression of Nek1 will be monitored carefully during kidney development and cystogenesis in the nek1 null mice. Nek1 null kidney cells will be cultured from the mice and used ex vivo to examine the effects of Nek1 and nek1 mutants in a null background. Finally, in aim 3, the interaction
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between Nek1 and VDAC1, a mitochondrial ion channel potentially involved in apoptotic pathways, will be analyzed by molecular and physiological methods. The significance of the interaction in the pathogenesis of PKD will be explored. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •
Project Title: NEUROPROTECTIVE EFFECTS OF MINOCYCLINE IN LENTIVIRAL INF Principal Investigator & Institution: Zink, M C.; Professor; Comparative Medicine; Johns Hopkins University 3400 N Charles St Baltimore, Md 21218 Timing: Fiscal Year 2004; Project Start 01-APR-2004; Project End 31-MAR-2009 Summary: (provided by applicant): HIV CNS disease is consistently associated with infiltration and activation of macrophages/microglia, enhanced production of proinflammatory cytokines, increased expression of proapoptotic and neurotoxic mediators, and neuronal loss. A number of neuroprotective therapeutics are being examined, but no single agent has emerged as the solution to the inflammatory and neurodegenerative effects of HIV in the CNS. The recent identification of the tetracycline derivative, minocycline, as a potent anti-inflammatory and neuroprotective drug that also inhibits HIV replication in macrophages, microglial cells, and astrocytes demands the examination of this readily available generic drug as a neuroprotective agent in HIV infection. We have developed an accelerated, consistent SIV/macaque model (SIV-AC) of HIV CNS disease in which over 90% of infected animals develop encephalitis with neurodegeneration as evidenced by increased expression of B-APP and B-amyloid and evidence of neuronal degeneration/apoptosis in the CSF and brain. This model recapitulates the acute, asymptomatic, and terminal characteristics of HIV infection in humans on a highly reproducible time schedule. Our recent studies using this model have demonstrated that the development of SIV encephalitis coincides with an imbalance between the antiapoptotic ERK signaling pathways and the proapoptotic JNK and p38 signaling pathways, representing a failure to maintain a homeostatic balance in the CNS. Our hypothesis is that minocycline will play a dual neuroprotective role in SIV-infected macaques: a) by inhibiting pathologic activation of p38 thus reestablishing a balance between pro-and antiapoptotic pathways, and b) by inhibiting SIV replication and hence the production of viral neurotoxic proteins in the CNS. This application proposes integrated in vivo and in vitro studies to examine the mechanisms by which minocycline exerts its palliative effects on the CNS. In Aim 1 we propose to measure the effects of minocycline on virus replication and on the development of CNS inflammatory and neurodegenerative changes in SIV-infected macaques. In Aims 2 and 3 we will identify the mechanism(s) by which minocycline protects against neurotoxicity and suppresses SIV/HIV replication in macrophages, microglia and astrocytes. Theses mechanistic studies are important given the potential of minocycline to act not only as a neuroprotective agent but also as a viral suppressive agent in the CNS. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen
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Project Title: NRG1 REGULATION OF CANDIDA ALBICANS VIRULENCE Principal Investigator & Institution: Lopez-Ribot, Jose L.; Associate Professor; Medicine; University of Texas Hlth Sci Ctr San Ant 7703 Floyd Curl Dr San Antonio, Tx 78229 Timing: Fiscal Year 2003; Project Start 01-APR-2003; Project End 31-MAR-2005 Summary: (provided by applicant): Candida albicans is the most common etiological agent of candidiasis, now the fourth leading cause of nosocomial infections. C. albicans is able to undergo reversible morphological transitions between unicellular yeast-like
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forms (blastospore) and filamentous forms (called hypha or pseudohypha depending on slight variations in the structure of the filament). These morphogenetic conversions are pivotal to its pathogenic potential. This belief is based upon the results obtained from a large number of virulence studies using C. albicans mutant strains unable to undergo this morphogenetic switch (i.e. delta cph1, delta efg1, delta tup1). However, all these strains are locked in one or other form so conclusions on the role of the morphogenetic transitions in virulence cannot be adequately addressed. Also, these mutant strains have been constructed using the URA-blaster technique with inherent problems that place serious questions on the genetic homogeneity between parental and disrupted strains. To overcome these problems, we have constructed a C. albicans strain which in which we have placed the recently discovered NRG1 gene under the control of a tetracyclineregulatable promoter. In C. albicans, Nrg1p is a DNA-binding protein that functions as a negative regulator of filamentation. Experiments confirmed the ability of doxycycline (DOX) to control the morphological transitions in this strain under a number of laboratory conditions. This gene expression system has also the advantage that it can be used in an animal host where expression of the gene of interest is regulated by simply adding DOX to the drinking water. The specific aims of this proposal are: i) to use this strain in a murine model of candidiasis in order to assess the role of NRG1 and the morphogenetic conversions in C. albicans virulence and ii) to identify downstream targets of Nrg1p under both planktonic and biofilm growing conditions. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •
Project Title: NUCLEAR FACTOR KAPPA B IN SEPTIC SHOCK Principal Investigator & Institution: Liu, Shu F.; North Shore-Long Island Jewish Res Inst Jewish Research Institute Manhasset, Ny 11030 Timing: Fiscal Year 2003; Project Start 01-AUG-2003; Project End 31-JUL-2008 Summary: (provided by applicant): Septic shock is a leading cause of death in the intensive care unit. A major hurdle in the clinical management of septic shock is the redundancy of mediators involved its pathophysiology, and the inability to inhibit multiple mediators simultaneously. NF-KappaB plays a crucial role in LPS- or cytokineactivated promoter activity of over 100 genes, many of which play important roles in septic pathophysiology. NF-KappaB could be an ideal target for the development of more effective therapeutic intervention for septic shock. However, two critical questions remain to be answered. First, how critical is NF-KB in mediating the in vivo expression of multiple proinflammatory genes induced by bacterial endotoxin? Second, is blocking NF-KappaB pathway beneficial or detrimental, and when and where to block this pathway, if it is proven to be beneficial? The goal of this application is to address these two questions. Our hypotheses are that NF-KappaB is a central common pathway in LPS-induced multiple proinflammatory gene expression and LPS-triggered septic pathophysioiogy, and that endothelial-selective blockade of NF-KappaB activation is beneficial to the prognosis of septic shock. We will generate two double transgenic mouse lines that conditionally overexpress the degradation-resistant l-KappaBalpha (IKappabalpha-mt), a potent inhibitor of NF-KappaB activation, selectively in endothelial cells (VecadrtTA/I-Kappabalphamt) and non-selectively in all cell types (CMVrtTA/IKappabalphamt) using a tetracycline-regulated gene expression system. We will study gene expression profiles of wild type and of CMVrtTA/I-KappaBalphamt mice after being challenged with LPS using microarray technique to define the in vivo function of NF-KappaB in mediating multiple proinflammatory gene expression. We will define the mechanistic role of NF-KappaB in septic pathophysiology. We will compare the efficacy of endothelial versus universal overexpression of I-KappaBalphamt in inhibiting
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multiple proinflammatory gene expression, in ameliorating septic pathophysiology. We will monitor and compare the mortality of wild type, VecadrtTA/I-KappaBalphamt and CMVrtTA/I-KBcmt mice in LPS- and CLP-induced septic shock models. We will study the effects of endothelial selective versus universal blockade of NF-KappaB activation on host defense functions against bacterial pathogens (bacterial clearance, macrophage or PMN phagocytosis). Results from our studies will provide an experimental basis and rationale for targeting NF-KappaB pathway as a novel therapeutic strategy for the treatment of septic shock. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •
Project Title: NUCLEIC ACID PROBES OF RIBOSOMAL STRUCTURE AND FUNCTION Principal Investigator & Institution: Cooperman, Barry S.; Professor; Chemistry; University of Pennsylvania 3451 Walnut Street Philadelphia, Pa 19104 Timing: Fiscal Year 2002; Project Start 01-AUG-1995; Project End 31-MAR-2004 Summary: The ribosome is the unique site of protein biosynthesis in all cells, and as such a detailed understanding of its structure and function is of fundamental importance to the more general understanding of cellular function at the molecular level. Aside from its intrinsic importance to the basic comprehension of life processes, better understanding of ribosomal function could have important therapeutic consequences. Many antibiotics in current clinical use, such as tetracycline, erythromycin and other macrolides, neomycin and other aminoglycosides, and chloramphenicol target ribosomes as their sites of action. Interest in these ribosomal antibiotics has been growing as bacterial resistance to beta-lactams and quinolines has become more widespread. Several drug companies are now devoting considerable resources toward synthesizing analogues and derivatives of ribosomal antibiotics that overcome bacterial resistance. Better understanding of ribosomal structure and function will be especially important for antibiotics, such as macrolides, where resistance is based on changes in ribosome structure. Our studies will be carried out on the E. coli ribosome, which is by far the best characterized by the studies of many groups, including our own. However, given the considerable conservation of ribosome structure throughout evolution the results we obtain should also be useful for understanding ribosomes from other organisms. The overall goal of this proposal is to describe conformational changes that the ribosome undergoes during specific steps of its functional cycle and how mutations and antibiotic binding affect these changes. We propose to do this by forming defined photocrosslinks from rRNA sites within the ribosome that have been targeted on the basis of their importance for ribosome structure and function, taking advantage of the intrinsic ability of the photocrosslinking process to sample all conformations in solution. Such crosslinks will be formed in different functional states, in wild-type and mutant ribosomes, and in the presence and absence of antibiotics. The structural constraints represented by such crosslinks, along with constraints generated by other approaches, will be used to model structures of the ribosome in specific functional states, using crystal structures of 70S ribosomes and 30S and SOS subunits as initial structures. As our major approach we will continue and refine the use of radioactive, photolabile derivatives of oligonucleotides having sequences complementary to rRNA sequences (PHONTs). Such probes bind to their targeted sequences in intact ribosomal subunits, and, on photolysis, incorporate into neighboring ribosomal components that can subsequently be identified. We also will develop a second approach based on site-specific introduction of photolability into intact rRNA (IPHOR - intact photolabile RNA) to obtain similar information for rRNA
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sites that are either inaccessible to PHONTs or where the use of PHONTs induces major conformational change. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •
Project Title: P53 MODIFICATION AND NOVEL BIOLOGICAL FUNCTIONS Principal Investigator & Institution: Stark, George R.; Professor; Cleveland Clinic Foundation 9500 Euclid Ave Cleveland, Oh 44195 Timing: Fiscal Year 2002; Project Start 01-SEP-1993; Project End 31-MAR-2003 Summary: p53 plays a central role in determining how mammalian cells respond to stress. DNA damange, arrest of DNA or RNA sythesis, and inhibition of pyrimidine nucleotide synthesis all lead to both the accumulation and activation of p53. It is likely that modulation of the phosphorylation of serine residues plays a key role in each process, and acetylation of lysine residues may also be important. We have established a valuable experimental system, based on the human MDAH041 fibroblast cell line, derived from a Li-Fraumeni patient and lacking p53 protein. Re- expression of wild-type p53 at normal basal levels restores many normal p53-dependent properties to these cells. Using this system, we have discovered a novel p53-dependent cell cycle checkpoint which prevents entry into mitosis when DNA synthesis is blocked (by hydroxyurea). We will investigate in detail the mechanisms through which p53 mediates this important response and will also take advantage of this system to investigate how a wide range of normal p53 responses to stress are affected by mutation of key serine and lysine residues. The major underlying hypothesis is that different stresses cause distinct modifications of p53, and that differently modified p53 molecules effect distinct and different cellular responses. Aim 1: Determine the roles of specific amino acid residues in different p53-dependent responses. We will mutate multiple serine and lysine residues that are sites of covalent modification of p53 and study the effects in MDAH041 cells. Basal expression of p53 variant proteins from a tetracycline-inducible promoter will be normalized by adjusting the amount of tetracycline. The following important p53-dependent responses will be assayed: (1) The accumulation of p53 protein, (2) the ability of p53 to bind to known regulatory proteins, (3) the activation and repression of transcription, (4) the ability to block entry into mitosis when DNA synthesis is arrested, (5) the ability to block entry into S phase when DNA is damaged, (6) the ability to block entry into S phase when mitosis is arrested, (7) the ability to induce a fragile site on chromosome 17 and (8) the inability to give rise to N-(phosphonacetyl)-L-aspartate (PALA)-resistant colonies. The information obtained will help to define discrete pathways that modify p53 in response to different activating signals and discrete functions that depend on the patterns of modification. Aim 2: Investigate the mechanisms through which p53 mediates a novel biological response. We will investigate how p53 interacts with or affects known components that govern entry into mitosis, especially cyclin B1 and CDC2, and how these interactions are affected when specific covalent modifications of p53 are prevented by point mutations. Understanding the complexity of p53 activation and function is important in developing strategies to deal more effectively with the regulatory circuits involved in the origin and progression of tumors and will also be important in helping to understand the p53 dependence of the toxicity of chemotherapeutic agents now in use. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen
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Project Title: P53 TARGET GENES IN APOPTOSIS Principal Investigator & Institution: Liang, Peng; Associate Professor; Cancer Biology; Vanderbilt University 3319 West End Ave. Nashville, Tn 372036917
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Timing: Fiscal Year 2004; Project Start 01-APR-2004; Project End 31-MAR-2008 Summary: (provided by applicant): Differential display (DD) is one of the most commonly used approaches for identifying differentially expressed genes. Despite the great impact of the method on biomedical research, there has been a lack of automation of DD technology to increase its throughput and accuracy for a systematic gene expression analysis. Most of previous DD work has taken a "shot-gun" approach of identifying one gene at a time, with a limited PCR reactions set up manually, giving DD a low-tech and low-throughput image. With our newly solved DD mathematical model, which has been validated by computer simulations, global analysis of gene expression by DD technology is no longer a shot in the dark. After identifying the "rate-limiting" factors that contribute to the "noise" level of DD method, we have optimized the DD process with a new platform that incorporates fluorescent digital readout and automated liquid handling. The resulting streamlined fluorescent DD (FDD) technology offers an unprecedented accuracy, sensitivity and throughput in comprehensive and quantitative analysis of gene expression. We plan to apply this newly integrated FDD technology to conduct a systematic and comprehensive screening for p53 tumorsuppressor gene targets using two well-defined biological systems which features tetracycline regulated expression of wild-type p53 in both colon cancer and lung cancer cells that undergo rapid apoptosis upon p53 induction. The p53 target genes identified will be subjected to secondary screening processes, including the use of methods independent of FDD, and an additional cell system where endogenous p53 can be activated by DNA damaging agents. In the final phase of this study, three other technologies, namely, the inducible enhanced green fluorescence protein (EGFP) coexpression system, in-frame GFP fusion expression system and mammalian RNA interference (RNAi), will be incorporated to provide functional identification and subcellular localization of p53 target genes involved in apoptosis. We anticipate that this systematic and pioneering study will not only uncover many (if not all) additional target genes of the most important tumor-suppressor gene, but also will provide an experimental basis for an objective comparison of major technologies for analysis of differential gene expression, in terms of accuracy, comprehensiveness and throughput. Such a cross-platform comparison in studying the same biological system will be crucial in pinpointing the strength and weakness of each method and helpful for future improvement of the next generation technologies through complementation, integration and refinement. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •
Project Title: PENICILLIN-RESISTANT NEISSERIA GONORRHOEAE (CMRNG) Principal Investigator & Institution: Nicholas, Robert A.; Pharmacology; University of North Carolina Chapel Hill Aob 104 Airport Drive Cb#1350 Chapel Hill, Nc 27599 Timing: Fiscal Year 2002; Project Start 01-APR-1996; Project End 31-MAY-2006 Summary: Antibiotic resistance in Neisseria gonorrhoeae remains a very important problem. Penicillin and tetracycline, which were once the antibiotics of choice for treatment of gonococcal infections, are no longer used due to the preponderance of strains resistant to these agents. Resistance to currently recommended antibiotics is also increasing. My laboratory is interested in the mechanisms of chromosomally-mediated antibiotic resistance in the gonococcus, especially those that promote high- level resistance and subsequent treatment failure. Intermediate- level chromosomallymediated resistance to penicillin and tetracycline is due to three resistance loci. These include the penA gene encoding altered forms of penicillin-binding protein 2 (PBP 2), the mtr loci conferring resistance to hydrophobic agents, and the penB gene, which
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decreases outer membrane permeability. The genes involved in mediating high-level penicillin resistance, however, have been difficult to identify. Our work during the last funding period has identified two resistance genes, ponA and penC, which together mediate high- level penicillin resistance, and a third gene, tetGC, which confers highlevel tetracycline resistance. This proposal outlines experiments to clone and characterize the penC and tetGC genes and to elucidate the mechanisms by which they increase resistance. In addition, we propose experiments that follow up on our structure/function studies of the penB gene product, porin IB, to understand how mutations in this protein increase both penicillin and tetracycline resistance. We also propose studies to complete our work on the crystal structure of penicillin- binding protein 2 (PBP 2), an essential penicillin target, and several mutant forms that display a lower affinity for beta- lactam antibiotics. In addition, we will engage in new structural studies of wild-type and mutant forms of porin IB to explicate in molecular detail how mutations in this protein decrease antibiotic permeability. The combination of genetic, biochemical, biophysical, and structural approaches outlined in this proposal will provide important insight into the mechanisms by which this important human pathogen becomes resistant to antibiotics. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •
Project Title: PHASE III TRIAL OF MINOCYCLINE IN ALS: DATA CENTER Principal Investigator & Institution: Miller, Robert G.; California Pacific Med Ctr-Pacific Camp 2200 Webster Street, Suite 514 San Francisco, Ca 94115 Timing: Fiscal Year 2003; Project Start 15-AUG-2003; Project End 31-MAY-2007 Summary: (provided by the applicant): This proposal is designed to provide data management and statistical support for the companion application Phase III Trial of Minocycline in ALS: I-Clinical Center (P.I. Paul Gordon, University of New Mexico), which is a multi-center clinical trial of Minocycline in ALS. The clinical trial is a randomized (1:1), double-blind, placebo-controlled trial, which will enroll 400 patients during the first two years. Each patient will be followed monthly for a minimum of 13 months; the first four months without drug or placebo (monitoring phase) to measure rate of decline of a validated functional measure (ALS Functional Rating Scale-Revised, ALSFRS-R), followed by 9 months on drug or placebo (assigned by randomization). The primary test of drug efficacy will be based on comparing changes in slope, i.e., the slope after assignment (based on up to 9 monthly scores), minus the slope before assignment (based on 5 monthly scores), in the drug vs. placebo groups. A linear mixed effects model will be used to estimate the average change of slope for patients in each group. The difference in average change, drug vs. placebo, will be tested using a mixed linear effects model. The study has 80% power to detect a change of 15% in slope, which corresponds to 4-5 months of prolonged survival. The companion application, Phase III Trial of Minocycline in ALS: I - Clinical Center (P.I. Paul Gordon, University of New Mexico), describes the details of background, clinical procedures and human subjects. This application describes the specific aims of the Data Management Center, and summarizes results of our previous clinical trials and studies in ALS. We provide data from our previous studies to justify the 4-month lead-in, thereby reducing sample size. We present an analysis of our previous results to support our choice of the primary and secondary efficacy variables. In particular, we demonstrate a close relationship between changes in ALSFRS and survival. We explain the selection of the effect size and development of the sample size in detail, based on analysis of our previous results. The details of data management are described, including the methods for quality control, security and information technology. Finally, the analytic plan is described in full.
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Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •
Project Title: PHASE III TRIAL OF MINOCYCLINE IN ALS:I-CLINICAL CENTER Principal Investigator & Institution: Gordon, Paul H.; Neurology; Columbia University Health Sciences Po Box 49 New York, Ny 10032 Timing: Fiscal Year 2003; Project Start 25-AUG-2003; Project End 31-MAY-2007 Summary: (provided by the applicant): Amyotrophic lateral sclerosis is a progressive neurodegenerative disorder leading to death on average in 3 years (1). There is no cure or known treatment that significantly improves function. Loss of motor neurons in the brain and spinal cord of ALS patients causes the progressive symptoms. Motor nerve degeneration may result from a cascade of events including free radical toxicity, glutamate excitotoxicity and mitochondrial dysfunction (2-4), which lead to the activation of cell death pathways (5-9). Mitogen-Activated Protein (MAP) kinases, including p38, are up-regulated in response to cell stress, and promote pro-apoptotic and inflammatory mediators (10, 11). Caspase enzymes and inflammatory mediators regulate cell death pathways (12-14), and are activated in human and transgenic mousemodel ALS (15,16). Caspase enzyme inhibitors and anti-inflammatory agents have been shown to slow progression in the ALS model (6,7,17,18). Minocycline, FDA approved for treatment of infection, has high central nervous system penetration when taken orally, inhibits p38 MAP kinase, prevents activation of caspase-1, caspase-3 and inflammatory mediators (19,20), and delays disease progression in animal models of neurodegenerative disorders, including Huntington disease (19), Parkinson disease (21) and ALS (22) (Serge Przedborski, personal communication). It is well-tolerated as an oral treatment for outpatients. The objective of this clinical trial is to determine whether Minocycline slows disease progression and helps maintain function in patients with ALS. The study design selects patients early in the course of ALS when a neuroprotective therapy may be most beneficial, measures functional improvement from the medication, which patients and physicians consider most important, and minimizes subject drop out. The proposed study will be an IRB-approved, investigatorinitiated, multi-center, randomized, double-blind, placebo-controlled study of Minocycline in 400 subjects with ALS treated for 9 months. The primary outcome measure is the change in slope of the revised ALS Functional Rating Scale (ALSFRS-R). Secondary outcome measures consist of changes in disease progression rate, as measured by Manual Muscle Testing (MMT), forced vital capacity (percent predicted) and survival. Should Minocycline prove effective in slowing the rate of functional decline, it would have an immediate impact both clinically and from the perspective of understanding the underlying pathophysiology of human ALS. This application is the clinical part of a combined proposal to carry out the clinical trial. A Data Center will be established at the California Pacific Medical Center in San Francisco to carry out data management and statistical analyses (see companion grant application Phase III Trial of Minocycline in ALS: II Data Center. P.I. Dr. Robert Miller). Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen
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Project Title: PROLACTIN AS A GROWTH FACTOR IN BREAST CANCER Principal Investigator & Institution: Ben-Jonathan, Nira; Professor; Cell Biol, Neurobiol/Anatomy; University of Cincinnati 2624 Clifton Ave Cincinnati, Oh 45221 Timing: Fiscal Year 2004; Project Start 15-FEB-2004; Project End 31-JAN-2009 Summary: (provided by applicant): Breast cancer is affected by genetic, environmental, dietary and hormonal factors. The role of prolactin (PRL) in mammary tumorigenesis in
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rodents is well accepted but its involvement in human breast cancer has been controversial. PRL is a pleiotropic hormone that is produced by pituitary and nonpituitary sites under dissimilar regulatory mechanisms. Recent studies revealed expression of PRL and its receptor (PRL-R) in the human breast but the cell type that produces PRL, the regulation of its expression and whether local PRL promotes breast cancer growth in vivo have not been resolved. Preliminary Results: We found de-novo synthesis and time-dependent increases in PRL expression and release from human breast explants. PRL production was significantly higher in adipose than in glandular or malignant tissues. PRL expression was induced early during differentiation of breast preadipocytes whereas the expression of its receptor (PRLR) increased progressively, paralleling the rise in ieptin. Both PRL and the PRL-R were also expressed in two human liposarcoma cell lines. To test the concept that locally-produced PRL promotes tumor growth, the PRL transcript was stably transfected into breast cancer cells. Clones overexpressing PRL grew faster than controls in vitro and formed faster growing tumors in nude mice. Tumors derived from the PRL-overexpressing clones had increased levels of the PRL-R and the anti-apoptotic agent Bcl-2. Our main premise is that breast adipose tissue is the major source of local PRL which acts as a cytokine to promote tumor growth. To gain more understanding of breast adipose PRL, we will first determine the biochemical properties and regulation of PRL and its receptor in breast adipose tissue and preadipocytes. We will then generate cancer cells with a tetracyclineinducible PRL expression and analyze the mechanism by which paracrine/autocrine PRL stimulates tumor growth in vitro and in vivo. Hypothesis: Adipose PRL production is normally suppressed by tonic inhibition, but tumors produce PRL stimulatory factors that overcome this inhibition. The rise in local PRL activates mitogenic and antiapoptotic signaling that stimulate tumor growth. Specific Aim 1 will characterize PRL and its receptor in breast adipose tissue. \ Specific Aim 2 will define the control of PRL expression in breast preadipocytes and liposarcoma cells. Specific Aim 3 will examine the effects of inducible PRL expression on tumor growth and gene expression. Long Term Goal: To establish PRL as a mitogen/anti-apoptotic factor in breast cancer, serving as the foundation for the design of future breast cancer therapy. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •
Project Title: PROLIFERATION & MALIGNANT TRANSFORMATION OF MELANOCYTES Principal Investigator & Institution: Halaban, Ruth; Senior Research Scientist; Dermatology; Yale University 47 College Street, Suite 203 New Haven, Ct 065208047 Timing: Fiscal Year 2002; Project Start 01-MAR-1988; Project End 31-MAY-2004 Summary: Overview: Melanoma cells, unlike normal melanocytes, are in a perpetual mode of cell division regardless of extracellular inhibiting signals. Substantial evidence implicates contributions from at least two major processes to this aberrant behavior: a) loss of p16INK4a functional inhibition of cyclin dependent kinases 4 and 6 (CDK4/6); and b) aberrant expression of bFGF (basic fibroblast growth factor). Hypothesis: The two processes are intricately linked and cooperatively induce constitutive CDK activity and the accumulation of E2F transcription factor, both being known rate-limiting reactions in cell cycle progression. Specific Aims: Aim number 1: To establish the role of CDK inhibitors (CKI) and E2F transcription factor in bFGF mediated growth dysregulation. We will examine the oncogenic effect of ectopic bFGF or E2F expression in melanocytes deficient for genes encoding specific CKI. To this end we will infect wild-type or knockout mouse melanocytes, deleted for CKI p16, p2l or p27, or the transcription factor E2F1 with a tetracycline(tet)-inducible retroviral vector encoding bFGF or E2F. The
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effect of transient versus sustained-expression of the ectopic genes on cell proliferation and tumorigenicity will be determined. Aim number 2. To identify the effector molecules for bFGF-mediated autonomous growth. CDK and E2F activities will be monitored as the melanocytes are induced to produce bFGF. Included are determinations of retinoblastoma tumor suppressor protein (Rb) abundance and phosphorylation levels, histone 1 phosphorylating activity, cyclin-associated kinase activity, E2F transcriptional activity, E2F/DNA complex association and expression of E2F-responsive genes. Aim number 3. To determine if inactivation of Rb and accumulation of E2F can be attributed to aberrant bFGF expression in autonomously proliferating human melanoma cells. We will examine the critical intermediates downregulated by disruption of the bFGF/FGF1 pathway in human melanoma cells in which the FGFR1 or bFGF have been neutralized by transfection with tet-inducible retroviral vector encoding a dominant-negative variant of the FGFR1 (dnflg) or antisense bFGF, respectively. Significance: Our unique cellular systems will enable us to systematically study the molecular changes induced by genetic alterations and aberrant expression of a growth factor identified in melanomas. Our functional studies may provide a basis for the design of new therapeutical agents for the treatment of patients with metastatic melanomas. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •
Project Title: PTP-MU REGULATES LUNG ENDOTHELIAL PARACELLULAR PATHWAY Principal Investigator & Institution: Goldblum, Simeon E.; Professor; Medicine; University of Maryland Balt Prof School Baltimore, Md 21201 Timing: Fiscal Year 2002; Project Start 01-APR-2002; Project End 31-MAR-2007 Summary: (provided by applicant): The endothelial cell (EC)-EC adherens junction or the zonula adherens (ZA) and the pulmonary vascular endothelial paracellular pathway are regulated, in part, through protein tyrosine phosphorylation. Several protein tyrosine phosphatases (PTPs) that associate with and/or dephosphorylate components of the ZA multiprotein complex appear to regulate the state of ZA protein tyrosine phosphorylation and assembly. One such PTP, PTP-mu, is highly expressed in lung tissue, almost exclusively expressed in EC, binds to the cytoplasmic domain of vascular endothelial (VE)-cadherin and/or to one or more of the catenins, and through its own ectodomain participates in homophilic adhesion. We will use an immortalized human microvascular EC line together with a tetracycline-responsive, retrovirus-mediated gene transfer system to stably overexpress wild-type PTP-mu, a dominant-negative catalytically-inactive PTP-mu and antisense PTP-mu together with coimmunoprecipitation, in vitro GST-fusion protein binding, and gel-overlay assays, fluorescence microscopy, phosphotyrosine immunoblotting, and actin pool measurements to address the following Specific Aims: 1) To determine whether PTP-mu catalytic function regulates the microvascular endothelial paracellular pathway; 2) To define the PTP-mu structural requirements for its association with VE-cadherin and/or other junctional proteins in human lung microvascular EC; 3) To identify the junctional and/or actin-binding protein substrates for PTP-mu in human microvascular EC. 4) To determine whether PTP-mu catalytic dysfunction disrupts the ZA-actin cytoskeletal linkage and/or induces actin reorganization; and 5) To determine whether PTP-mu overexpression protects against agonist-driven endothelial barrier disruption and/or enhances barrier recovery. These studies will test whether PTP-mu serves a counterregulatory role in the maintenance of basal pulmonary microvascular endothelial barrier
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function and/or participates in the opening of the paracellular pathway in response to established mediators of permeability. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •
Project Title: REGULATABLE EXPRESSION OF TRAIL AND VIRAL ONCOLYSIS Principal Investigator & Institution: Doronin, Konstantin; Virrx, Inc. 1609 Adgers Wharf Dr St. Louis, Mo 63017 Timing: Fiscal Year 2004; Project Start 01-APR-2004; Project End 31-MAR-2005 Summary: (provided by applicant): We have constructed an oncolytic adenovirus vector named "KD3" that replicates selectively in cancer cells as opposed to normal cells because of a mutation in the adenovirus E1A gene that prevents E1A proteins from deregulating the cell cycle in normal cells. KD3 was designed to overexpress the E311.6K protein (Adenovirus Death Protein, ADP). Overexpression of ADP allows for efficient egress of KD3 from infected cancer cells and the spread of KD3 from cell-to-cell. We also have constructed and partially characterized in cell culture a replicationdefective vector named "Tet-On-TRAIL" that expresses TNFrelated apoptosis-inducing ligand (TRAIL) under the control of a tetracycline-regulatable cassette. TRAIL is a member of the TNF family of death ligands that has been shown to induce apoptosis in a majority of cancer cells but not in most normal cells. When cells are co-infected with Tet-On-TRAIL and KD3, KD3 complements the replication and spread of Tet-OnTRAIL. When the Tet promoter is induced by doxyclycline (DOX), Tet-On-TRAIL synthesizes TRAIL very abundantly. We propose to characterize this "binary" vector system in cell culture and xenografts in nude mice with the long-term goal of obtaining preclinical data for a clinical trial. Tumors should be destroyed by two independent mechanisms, the replication and cell-to-cell spread of KD3 plus Tet-On-TRAIL, and the apoptosis-inducing ability of TRAIL on uninfected cancer cells. The vector system should be restricted to tumors by virtue of the E 1A mutation in KD3 and the cancer cell specificity of TRAIL. In cell culture experiments, we will examine TRAIL protein by immunoblot and immunofluorescence and TRAIL function by apoptosis assays. In order to determine if there is a bystander effect, cells infected with Tet-On-TRAIL+KD3+DOX will be mixed with uninfected cells and the death of the latter will be assayed. In vivo, we will inject Tet-On-TRAIL+KD3+DOX plus control vectors into subcutaneous human Hep3B liver cancer tumors in nude mice and examine the growth and apoptosis of the tumors, including uninfected contralateral tumors which may be destroyed by TRAIL released from the infected tumors. The possible toxicity to the mouse liver will be studied. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen
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Project Title: REGULATION OF EPITHELIAL CELL MOTILITY BY VILLIN Principal Investigator & Institution: Khurana, Seema; Associate Professor; Physiology; University of Tennessee Health Sci Ctr Memphis, Tn 38163 Timing: Fiscal Year 2004; Project Start 01-APR-2004; Project End 31-MAR-2009 Summary: (provided by applicant): The PI proposes to determine and characterize the role of villin and its ligands (phosphatidylinositol 4,5- bisphosphate (PIP2) and actin) in epithelial cell motility. Active cell motility regulates many important intestinal epithelial cell functions, including: ion transport proteins via endocytosis and exocytosis, crucial for absorption of nutrients; intestinal restitution, important to maintain homeostasis in the presence of large osmotic and mechanical stress; the movement of cells along the crypt-villus axis; the invasion and propagation of enteropathogens; immune
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surveillance and inflammation; as well as neoplastic tumor cell dissemination and metastasis. Villin is an actin nucleating, capping, severing, and bundling protein. Villin binds and regulates two ligands that are known to regulate cell motility, phospholipase C-gamma1 (PLC-gamma1) as well as the substrate of the lipase namely, phosphatidylinositol 4,5-bisphosphate (PIP2). Recent studies with villin knock out mice have demonstrated that villin is necessary to regulate epithelial cell motility. In addition, villin shares sequence homology with other proteins of its family including gelsolin, which have been shown to regulate cell motility in vivo. Our working hypothesis is that villin's ability to regulate phosphoinositide-mediated signal transduction pathways and the actin cytoskeleton is important to epithelial cell physiology and pathophysiology involving changes in cell motility. To accomplish our overall study objectives we will characterize the villin-PIP2 interaction using the following approaches: reconstitution in vitro using recombinant villin proteins; endogenous villin expression in the intestinal epithelial cell line, Caco-2; and over expression of villin and enzymes that regulate intracellular PIP2 levels, in the villin null intestinal cell line, IEC-6 using a tetracyclineregulated system. To determine unequivocally the role of villin in the epithelial cell motility, we will use villin knock out mice. These studies promise the prospect of modifying motility for enhancement of normal physiology and for amelioration of disease. Inhibition of epithelial cell motility can be significant in several diseases, including inflammatory bowel disease, celiac disease, and colon cancer. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •
Project Title: REGULATION OF GLUTATHIONE SYNTHESIS IN OXIDATIVE STRESS Principal Investigator & Institution: Forman, Henry J.; Professor; Environmental Health Sciences; University of Alabama at Birmingham Uab Station Birmingham, Al 35294 Timing: Fiscal Year 2002; Project Start 15-APR-1996; Project End 31-MAR-2005 Summary: (Adapted from the Investigators abstract). This proposal focuses on the signal transduction mechanisms regulating the increase in de novo glutathione (GSH) synthesis that occurs during adaptation to oxidants and other electrophiles. GammaGlutamylcysteine synthetase (GCS), the rate limiting enzyme in de novo GSH synthesis, is composed of two subunits. Both GCS genes are transcriptionally up-regulated in response to stress from oxidants and electrophilic xenobiotics. Nonetheless, a mismatch between expression of the two GCS subunit proteins may result in altered kinetics and/or decreased stability of the enzyme. gamma-Glutamyl transpeptidase (GGT) is an exoenzyme that provides substrates for GSH synthesis by breaking down extracellular GSH. GGT enzymatic activity and mRNA transcription also increases in response to oxidants. While much has been learned over the past few years regarding mechanisms of GSH increases in adaptation, the signaling mechanisms that govern regulation of GCS and GGT on the transcriptional, post-transcriptional and post-translational levels remain largely unresolved. The investigators propose to test the following hypotheses in three aims: 1- that signaling for the transcriptional activation of GCS genes by electrophiles and H2O2-generating compounds occurs through overlapping pathways; 2- that the GCS regulatory subunit (GCS-LS) stabilizes the catalytic subunit against proteolysis as well as regulates the kinetics; 3- that GGT transcription by reactive oxygen species is mediated through activation specific signaling pathways and cis acting element(s) activated by H2O2. These hypotheses will be tested using the agents (2,3dimethoxy-1,4-naphthoquinone (DMNQ), 4-hydroxynonenal (4HNE), and betanaphthoflavone (BNF)) at concentrations and incubation times that cause increased transcription of both GCS subunits. Methods to be used include, dominant negative and
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constitutively active signaling components, kinase assays, in vivo footprinting, reporter construct, tetracycline regulated antisense transfection, and measurement of reactive oxygen species, glutathione oxidation and alpha-unsaturated aldehydes. These aims will be carried out by using established cell models modified as needed to determine whether the conclusions are unique or generally applicable. The long-range goal of their research is an understanding of the regulation of GSH synthesis and the potential for its pharmacological manipulation to enhance synthesis of this essential cellular constituent. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •
Project Title: REPLICATION CONTROL IN FRAGILE X SYNDROME Principal Investigator & Institution: Boggs, Barbara A.; Molecular and Human Genetics; Baylor College of Medicine 1 Baylor Plaza Houston, Tx 77030 Timing: Fiscal Year 2003; Project Start 15-APR-2003; Project End 31-MAR-2005 Summary: (provided by applicant): Fragile X syndrome, which is one of the most common forms of inherited mental retardation, has been shown to result from mutation of the FMR1 locus at Xq27.3. The most frequent mechanism of mutation is expansion of a polymorphic CGG sequence located in the 5'-untranslated region of the gene past a threshold of about 200 repeats; this sequence is normally heavily methylated, which causes transcriptonal inactivation. The protein encoded by the FMR1 locus (FMRP) has been found in large ribonucleoprotein particles in the cell and it appears to specifically interact with a subset of mRNA species on translating polyribosomes; loss of functional protein then may result in translation dysregulation of these downstream genes. Another intriguing property of the locus in patient cell lines is delayed replication of a chromatin domain 10-20 times the size of the gene itself, which is likely to play a role in the characteristic observation of a "fragile" site at this position. The investigators have made the surprising observation that this late replication phenotype is also found in cell lines with non-expansion mutations, including a large deletion in the 5' region, a single base deletion that leads to a frameshift and premature termination and a splice site mutation. The simplest explanation of this finding is that the FMRP protein is involved directly or indirectly (through chromatin modification, for example) in regulation of replication properties at this locus, and possibly others. The goal of this application is to test this hypothesis. To accomplish this, the investigators will use a fluorescence in situ hybridization technique to examine replication timing in additional cell lines from patients with non-expansion mutations, including a missense mutation that affects one of the primary RNA binding domains and microdeletions affecting gene expression. In addition, they will examine replication in cell lines from "high-functioning" males, where it is postulated that a deficiency in methylation allows functional protein production in spite of a full expansion of CGG nucleotides past the normal level of affected males. The investigators will also examine directly the role of FMR1 in replication control by either activating endogenous inactive genes or by attempted complementation of the late replication phenotype using transfection with tetracyclineinducible cDNA constructs or genomic BAC clones. Finally, the investigators wish to conduct some preliminary experiments to study potential replication phenotypes elsewhere in the human genome as well as in mouse cells. They feel these studies represent a novel approach to study the possible functional roles of FMRP within the cell which may, in turn, lead to a major new direction in the study of the etiology of fragile X syndrome. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen
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Project Title: RESCUE OF GUCY1*B PHENOTYPE USING SOMATIC GENE THERAPY Principal Investigator & Institution: Semple-Rowland, Susan Lynn.; Associate Professoir; Neuroscience; University of Florida Gainesville, Fl 32611 Timing: Fiscal Year 2003; Project Start 01-APR-1996; Project End 31-MAR-2007 Summary: (provided by applicant): The long-range goals of this research program are to understand the cellular consequences of Leber congenital amaurosis - 1 (LCA1) and to determine if therapies based on recombinant lentiviral vectors can be used to treat this devastating autosomal recessive retinal disease that results in blindness or severe visual loss in newborn infants. LCA1 is caused by mutations in the gene encoding photoreceptor guanylate cyclase -1 (GC1), the majority of which lead to loss of function of the GC1 enzyme. The GUCY1*B chicken, which carries a null mutation in GC1, is a naturally occurring model of LCA1 that possesses a cone-dominant retina and is blind at hatching. Analyses of this model, which serves as a focal point for this research program, provide a unique opportunity to improve our understanding of LCA1 and of cone responses to disease. Aim 1 of this proposal is to test the hypothesis that the expression of normal GC1 in GUCY1*B photoreceptors is sufficient to rescue photoreceptor function and prevent degeneration. Lentivirus carrying a GC1 transgene will be administered to GUCY1*B chickens during embryonic development and the effectiveness of the treatment will be assessed at 2-4 weeks of age by examining (1) the behavior of the animal, (2) the responsiveness of the retina to light by electroretinography, (3) retinal morphology, and (4) the expression of GC1 and guanylate cyclase activating protein -1. Aim 2 of this proposal is to determine the relationship between disease progression in GUCY1*B retina and the ability of our gene replacement strategy to rescue photoreceptor function. Since the GUCY1*B photoreceptor population is 80% cone, these studies will be particularly relevant to understanding cone disease and the responses of these cells to therapeutic treatment. Expression of the GC1 transgene in retina will be delayed until 10, 21 or 60 days after hatching and will be controlled by either placing the GC1 transgene under the control of a tetracycline-regulatable promoter or by varying the time of administration of the GC1 lentivirus. The efficacy of the delayed treatments will be assessed as described for Aim 1. The results of these experiments will improve our understanding of LCA1 and the potential usefulness of gene therapy to treat this disease. In addition, they will provide new information about the effectiveness of tetracycline-regulated expression systems to control the expression or therapeutic genes in the retina. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen
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Project Title: RESTENOSIS AND ENDOTHELIAL PROLIFERATION Principal Investigator & Institution: Losordo, Douglas W.; Chief, Cardiovascular Research; St. Elizabeth's Medical Center of Boston 736 Cambridge St Boston, Ma 02135 Timing: Fiscal Year 2002; Project Start 15-AUG-1999; Project End 31-JUL-2003 Summary: (Adapted from Investigator's Abstract): The overall goal of this research is to inhibit arterial restenosis by promoting better re-endothelialization of an arterial segment after angioplasty. The authors have obtained evidence that TNF is expressed at sites of balloon injury in vivo, and can inhibit endothelial proliferation in vitro. This TNF inhibition appears to work via a repression of the cell cycle regulatory factors E2F1 and cyclin A. They hypothesize that the in vivo expression of TNF is a major factor leading to delayed endothelial regrowth in the injured artery, and thereby promoting intimal thickening as a major part of the restenosis process. By extension, they have
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preliminary data indicating that E2F1 over expression in the artery wall can accelerate re-endothelialization and thereby inhibit restenosis. The resultant specific aims are therefore as follows: Investigate the role of E2F1 in re-endothelialization and restenosis after balloon angioplasty. They propose to characterize the effect of local overexpression of E2F1 (using adenoviral delivery) on re-endothelialization in the rat carotid injury model. These studies will then be complemented by an analysis of a newly developed mouse carotid artery injury model, using the E2F1 deficient mouse; both in the absence of E2F1, and after adding back E2F1 via adenoviral gene transfer. Investigate certain mechanisms involved in the inhibition of endothelial cell proliferation after balloon angioplasty. Here they plan to determine the molecular mechanisms relevant to TNF-induced inhibition of endothelial proliferation via the repression of E2F1 mRNA and protein expression, with the subsequent down regulation of cyclin A activity. Thus, with respect to the E2F1 gene, they will identify the cis-acting DNA sequences that regulate TNF mediated changes in E2F1 expression in endothelial cells, and characterize the trans-acting factors that bind to these elements. They will also determine the cis elements responsible for TNF-induced repression of cyclin A gene expression and similarly identify relevant trans-acting factors binding to these elements. Investigate the role of cyclin A in restoring proliferation of endothelial cells exposed to TNF. Additional data indicate that cyclin A over-expression alone is sufficient to overcome TNF-mediated endothelial cell growth arrest. They will therefore determine if cyclin A is capable of exerting independent proliferation and survival effects on TNF exposed endothelial cells by over-expressing cyclin A using a tetracycline-responsive inducible gene expression system. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •
Project Title: ROLE OF CONSTITUTIVELY ACTIVE CAMII IN MEMORY FORMATION Principal Investigator & Institution: Mehren, Jennifer; Biology; Brandeis University 415 South Street Waltham, Ma 024549110 Timing: Fiscal Year 2002; Project Start 01-FEB-2002; Project End 31-JAN-2005 Summary: (provided by applicant): Calcium/calmodulin dependent protein kinase II (CaMKII) is an important molecule involved in neuronal plasticity, including processes involved in memory formation. Its unique ability to become calcium-independent upon autophosphorylation is conserved in Drosophila and mammals, and mutating the threonine at residue 287 to aspartate can mimic this calcium-independent activity. The objective of this proposal is to develop a system for temporal control of gene expression in the CNS, and to use this system to investigate the role of calcium-independent CaMKII activity in memory formation. To this end, the tetracycline-dependent transactivator expression system will be used to restrict expression of a constitutively active form of CaMKII to relevant regions of the adult brain. Behavioral consequences will be measured in the courtship-conditioning assay. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen
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Project Title: ROLE OF IFI 16 IN CELLULAR SENESCENCE AND AGING Principal Investigator & Institution: Choubey, Divaker; Assistant Professor; Radiation Oncology; Loyola University Medical Center Lewis Towers, 13Th Fl Chicago, Il 60611 Timing: Fiscal Year 2003; Project Start 01-APR-2003; Project End 31-MAR-2005 Summary: This proposal addresses Research Objective # 14; Understand Healthy Aging Processes. Cellular senescence or replicative senescence refers to the irreversible cell
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cycle arrest displayed by cells that have exhausted their replicative potential. Based on several studies, it is evident that senescent cells accumulate with age in human tissues and organs where cell turnover is common. These studies also raise the possibility that the slow growth and metabolism of senescent cells can lead to tissue failure and degenerative diseases during aging. Additionally, bypassing of replicative senescence could lead to aging-related cancers. Therefore, identification of senescence genes and a clear understanding of their role in senescence pathways are needed to diagnose and treat aging-related diseases effectively. Although genetic studies have indicated that the long arm of human chromosome 1 harbors genes regulating senescence, the identities of these genes remain unknown. Our recent experiments indicated that levels of IFI 16 protein, encoded by the gene IFI 16 (location 1q22) from the 200-gene family, are higher in older populations of human fibroblasts than young fibroblasts. Based on this observation and others, we hypothesize that the gene IFI 16 is a candidate for regulating replicative senescence in culture and aging in vivo. Specific aim #1 : To investigate the role of IFI 16 in replicative senescence. We propose to: (i) study the kinetics of IFI 16 induction in human fibroblasts when they approach replicative senescence in culture; (ii) measure the induction of replicative senescence in human fibroblasts in which IFI 16 levels are decreased using an antisense approach; and (iii) measure the induction of senescence in human cell lines from the complementation group C (defective in chromosome 1) to see whether inducible (tetracycline-repressible) expression of IFI 16 in cells of these lines reverses the immortal phenotype. Specific aim #2: To elucidate the molecular mechanism(s) activating the expression of IFI 16 gene during the induction of replicative senescence in human fibroblasts. We will test whether the transcription factor KLF6, a candidate for tumor suppressor, activates transcription of the IFI 16 gene. Siqnificance: The proposed studies will test whether the gene IFI 16 is a candidate for regulating the replicative senescence. Importantly these studies will provide the preliminary data and evidence that we can perform these techniques for an R01 application. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •
Project Title: ROLE OF LAMININ 5 IN PROSTATE TUMORIGENESIS Principal Investigator & Institution: Calaluce, Robert; Pathology; University of Arizona P O Box 3308 Tucson, Az 857223308 Timing: Fiscal Year 2002; Project Start 11-APR-2001; Project End 31-MAR-2006 Summary: (provided by Applicant) The extracellular matrix (ECM) and its interaction with surrounding cells offers an exciting, largely unexplored area in prostate cancer biology. One pivotal ECM protein, laminin-5, has been shown to have altered expression in various tumors. We have demonstrated a loss of laminin-5 protein expression in prostate carcinoma but the mechanism underlying this loss is not completely understood. Our hypothesis is: The loss of laminin-5 expression in prostate epithelial cells is an essential event in tumor progression. We have proposed the following three specific aims to test this hypothesis. Aim 1. Determine whether the in vitro restoration of the laminin-5 beta-3 chain in LNCaP prostate carcinoma cells will restore hemidesmosome formation, integrin binding, and subsequent signal transduction. Aim 2. Determine whether the in vitro abrogation of the laminin-5 beta-3 chain in normal prostate epithelial cells will alter adherence, signal transduction, and cell maturation. Aim 3. Characterize the effects of the loss of the laminin-5 beta-3 chain in vivo by creating an organ-specific, tetracycline-induced, transgenic mouse model. The proposed study will clarify the mechanism of the loss of laminin-5 in prostate carcinoma. The candidate will provide new insights to the mechanism underlying this loss, under the
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guidance of Dr. Nagle who has made major contributions to understanding the role of laminin-5 in prostate neoplasia. In addition, the creation of a novel transgenic mouse model, under the direction of Dr. McDonald, will characterize the role of laminin-5 in normal prostate development and prostate tumorigenesis. The proposed award would provide an ideal means to extend this promising line of work and facilitate the candidate's long-term career objective to become an independent physician scientist investigating the role of ECM proteins in prostate carcinoma and determining their potential prognostic value. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •
Project Title: ROLE OF MYELOID ELF-1 LIKE FACTOR IN HEMATOPOIESIS Principal Investigator & Institution: Hedvat, Cyrus V.; Sloan-Kettering Institute for Cancer Res New York, Ny 10021 Timing: Fiscal Year 2002; Project Start 05-APR-2001; Project End 31-MAR-2006 Summary: (Adapted from applicant?s abstract) The ETS family of transcription factors play key roles in the regulation of hematopoiesis. ETS factors regulate critical events in hematopoietic development as demonstrated by the profound defects observed in mice deficient in these genes. The aberrant expression of ETS family members has been linked to the pathogenesis of several types of human and murine leukemia as well as other malignancies. MEF (myeloid elf-1 like factor) is a member of the ETS family cloned from a human megakaryocytic leukemia cell line (CMK). MEF activates transcription of genes important in hematopoiesis including the cytokines GM-CSF and IL-3. MEF interacts with the transcription factor AML1, and the AML1/ETO fusion protein, the product of the (8;21) translocation in acute myelogenous leukemia, and cooperates with AML1 in the regulation of the IL-3 promoter. To evaluate the role that MEF plays in hematopoietic cell development and function, the regulatory pathways central to MEF function will be defined. 1) A tetracycline-inducible MEF expression hematopoietic cell model will be used for differential gene expression analysis with DNA microarrays to identify target genes, which will be validated, and their regulation studied. 2) The functional domains of MEF that regulate the interaction with AML1B and cyclin A will be characterized and their role in regulating target gene expression will be studied. 3) the phenotype of MEF deficient mice generated by homologous recombination will be characterized to define the role of MEF in the development of the hematopoietic, as well as other, systems. Gross, microscopic, and cell-type specific functional abnormalities will be assessed with particular attention to the hematopoietic system. This work will contribute to defining the relationship between mechanisms of cellular development and differentiation and the establishment of disease. Work in the area of hematopathology where diagnostic skills will be developed. Experience in the analysis of mouse models, the use of emerging microarray technology to study and diagnose disease, and clinical diagnostic development will lead to an independent career as a physician scientist. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen
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Project Title: ROLE OF SLP-76 IN NAIVE AND MEMORY T CELL FUNCTION Principal Investigator & Institution: Maltzman, Jonathan S.; Medicine; University of Pennsylvania 3451 Walnut Street Philadelphia, Pa 19104 Timing: Fiscal Year 2003; Project Start 01-SEP-2003; Project End 31-MAY-2007 Summary: (provided by applicant): Mature T lymphocytes can be divided into at least three groups based on previous encounter with antigen. In contrast to naive cells,
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effector and memory T lymphocytes have previously encountered and been activated by interaction with an antigen presenting cell expressing a specific antigen in the groove of an appropriate MHC molecule. It has become clear that the signal generated by stimulation through the T cell receptor of these sub-populations of T cells is quantitatively and qualitatively different. Adaptor proteins are known to be critical for integration of signals in all cells. The SH2 domain containing Leukocyte Protein of 76 kilodaltons (SLP-76) is essential for both thymocyte development and mature T cell function. Unfortunately, because of the absolute dependence of SLP-76 expression during thymic development, there are no genetic models to study the function of SLP-76 in normally selected mature T cells; neither naive, effector, nor memory phenotype. Studies in primary murine T cells have shown that the level of SLP-76 protein expression is different in naive, effector and memory T cells suggesting the hypothesis that the requirements for SLP-76 expression and the specific molecular interactions differ in mature T cells of different functional phenotypes. To address this hypothesis, I propose to generate mice in which expression of SLP-76 is controlled by the administration of exogenous drugs. These mice will be utilized in in vivo infection models to evaluate the requirements for SLP-76 at different maturational stages. Mice conditionally expressing SLP-76 will be mated to mice with mutant forms of the protein to evaluate structure/function in vivo. This proposal describes a five-year training program with the goal of becoming an independent investigator in an academic setting. The principal investigator has completed clinical training in Internal Medicine and Nephrology and graduate training in immunology. Dr. Gary Koretzky will mentor the scientific and career development of the principal investigator. Dr. Koretzky is a leader in the fields of Immunology and signal transduction. He is director of the Signal Transduction Program at the University of Pennsylvania and has mentored numerous students and post-doctoral fellows. In addition to Dr. Koretzky, an advisory committee of physician-scientists has been formed to oversee scientific and career development. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •
Project Title: ROLE OF TGF-ALPHA IN PULMONARY VASCULAR DISEASE Principal Investigator & Institution: Le Cras, Timothy D.; Assistant Professor; Children's Hospital Med Ctr (Cincinnati) 3333 Burnet Ave Cincinnati, Oh 452293039 Timing: Fiscal Year 2003; Project Start 10-APR-2003; Project End 31-MAR-2007 Summary: (provided by applicant): Pulmonary hypertension plays a major role in the morbidity and mortality of a number of acute and chronic lung diseases including bronchopulmonary dysplasia. While clinical studies have implicated transforming growth factor-alpha (TGF-alpha) in the pathogenesis of these diseases, the role of TGFalpha, its cellular targets, and the signaling pathways involved are unclear. Preliminary data accompanying this application demonstrate that epithelial expression of TGF-alpha causes severe reductions in pulmonary artery number, vascular remodeling, and pulmonary hypertension as early as 2 weeks of age in transgenic mice. We also have preliminary evidence to suggest that this is mediated in part by autocrine signaling through EGF receptors on distal epithelial cells, and reductions in vascular endothelial growth factor-A (VEGF-A). Using both in vitro and in vivo approaches, this proposal will test the central hypothesis that epithelial expression of TGF-alpha disrupts vascular growth and causes vascular remodeling and pulmonary hypertension through EGF receptor-dependent autocrine-paracrine signaling. In the first phase we will define when pulmonary growth is disrupted by TGF-alpha, whether acute or chronic expression of TGF-alpha is necessary, and whether TGF-alpha causes vascular remodeling and pulmonary hypertension independent of reductions in vascular growth (Specific Aim 1).
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In the second phase we will define the role of indirect signaling through the epithelium versus direct signaling to the vascular endothelium (Specific Aim 2) using a dominant negative (mutant) EGF receptor to block TGF-alpha signaling in specific cellular compartments. In the third phase we will define whether TGF-alpha, regulates expression of VEGF-A in type II epithelial cells in vitro and in vivo, and whether reductions in VEGF-A contribute to the pathogenesis of pulmonary vascular disease (Specific Aim 3). The overall goal of this proposal is to define the timing, cellular targets, and mechanism by which TGF-alpha disrupts pulmonary vascular growth and causes pulmonary hypertension and vascular remodeling. This information will serve as a basis for developing therapeutic strategies aimed at improving lung growth and preventing pulmonary hypertension in premature babies and adults. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •
Project Title: SMART VIRUS VECTORS WITH A BUILT-IN SAFETY MECHANISM Principal Investigator & Institution: Verardi, Paulo H.; Interntl Lab Molecular Biology; University of California Davis Sponsored Programs, 118 Everson Hall Davis, Ca 95616 Timing: Fiscal Year 2004; Project Start 01-APR-2004; Project End 31-MAR-2006 Summary: (provided by applicant): Viruses are powerful tools for the development of vaccines and gene therapies. However, the safety of live recombinant vectors is always a concern, as uncontrolled replication or complications are not inconsequential, particularly in immunosuppressed individuals. In an effort to develop safer, yet still effective live viral vectors, we propose to construct fully replicating virus vectors with a safety mechanism designed to be used when complications with the vector occur or therapy needs to be stopped. Our SMART (Safety Mechanism Assisted by the Repressor of Tetracycline) virus vectors will use elements from the tet operon to regulate the expression of a "safety" gene. Vaccinia virus (VV) is an ideal vector system to test this strategy. The tet system has been successfully adapted to VV, allowing expression to be tightly regulated by the antibiotic tetracycline. In addition, we have shown that interferon-gamma (IFN-gamma) acts as a safety gene in vivo when expressed by VV, attenuating the virus by more than million-fold in immunodeficient mice. Our hypothesis is that live SMART VV vectors expressing a safety gene would be significantly safer: treatment of any adverse reactions would be as simple as antibiotic therapy, since it would allow the expression of the safety gene and significantly enhance virus clearance. More importantly, tetracycline treatment would only be needed when complications occur or are suspected, or when treatment should be stopped. Two specific aims will be addressed under this R21 application: (1) to develop SMART VV vectors expressing a safety gene only in the presence of inducer, and (2) to assess the safety and efficacy of the new vectors. First, SMART VV vectors expressing the tetracycline repressor under a constitutive VV promoter and the reporter gene green fluorescent protein (GFP) under an engineered inducible promoter will be generated and the induction of GFP will be examined in an effort to optimize the system. Then, a SMART vector inducibly expressing murine IFN-gamma, as a model safety gene will be developed. Normal and immunodeficient mice will be given the VV vector expressing IFN-gamma inducibly and survival, pock lesion resolution, disease recovery, weight loss, and virus replication will be assessed in the presence and absence of inducer. In addition, immune responses to VV will be assessed to ensure that the efficacy of the new vectors is not compromised by expression tetracycline repressor expression or tetracycline treatment. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen
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Project Title: SPECIALIZED CENTER OF RESEARCH IN HEART FAILURE Principal Investigator & Institution: Mann, Douglas; Professor; Medicine; Baylor College of Medicine 1 Baylor Plaza Houston, Tx 77030 Timing: Fiscal Year 2002; Project Start 17-FEB-1995; Project End 31-JAN-2005 Summary: The overall objective of the current SCOR and the Proposed Renewal is to elucidate the molecular basis for the long-term adaptive response of the heart to injury, both inherited and acquired, where manifested by hypertrophy or dilitation. This proposal encompasses 5 collaborative investigations, supported by integrated core facilities to address issues fundamental to the etiology, pathogenesis and treatment of cardiac failure. Novel genes will be identified responsible for inherited cardiac disorders, familial dilated cardiomyopathy (FDCM) manifested in the left ventricle and arryhthmogenic right ventricular dysplasia in the right ventricle, as paradigms of dilated cardiomyopathy, the most common form of acquired heart failure. To date, two genes (cytoskeletal) have been identified that cause DCM, actin and desmin. Thus, cytoskeletal proteins may provide a unifying causality for DCM analogous to that of sarcomeric proteins for HCM. Accordingly, insight gained from expression of the mutant desmin in the transgenic mouse should have pathogenetic implications for DCM due to other defective cytoskeletal proteins, whether familial or acquired. While assembly and organization of the cytoskeletal components are an integral part of the cardiac growth response, their role as heretofore been ignored until the identification of the integrin signaling pathway (RhoA, Focal Adhesion Kinase, and Integrin Linked Kinase). In Dr. Schwartz' project, dominant negative mutants of these molecules will be used in cardiac myocytes and Gene-Switch transgenics to determine whether one or all of these are necessary for cytoskeletal assembly and hypertrophy. FHCM, due to over 100 mutations in seven genes, develops the secondary phenotype of increased fibrosis and hypertrophy, providing the opportunity for prevention. Renin-angiotensin system (RAS) inhibitors will be assessed in transgenics harboring the human cTNT mutation and, in preparation for future gene therapy, Gene-Switch will be used to determine if the phenotype is reversible. Growth factor(s) responsible for the secondary phenotype will be sought through subtraction hybridization. A novel pathway (TNFalpha) shown in the current SCOR to play a pivotal role in the growth response (hypertrophy) and heart failure (apoptosis), will be pursued to identify molecular interaction with RAS, both in genetic models and in patients with heart failure and to develop novel specific therapies. Strategies to achieve the aims, will utilize "state of the art" techniques: automated genetic analyzers for genotyping and DNA sequencing, BACs, YACs, and DNA microchip arrays to identify genes, the RU-486 Gene Switch to regulate expression of transgenes, PCR-generated dominant negative mutants, "gutless" tetracycline dependent adenoviral vectors, selective elimination of genes (knock-out mice), and Ta178 radionuclide angiography to assess mouse cardiac function. These studies elucidate further the molecular foundations of cardiac hypertrophy and failure and should provide a rational basis for more effective therapy. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen
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Project Title: THE ROLE OF GELATINASE A IN INTERSTITIAL FIBROSIS Principal Investigator & Institution: Cheng, Sunfa; Northern California Institute Res & Educ 4150 Clement Street (151-Nc) San Francisco, Ca 941211545 Timing: Fiscal Year 2002; Project Start 01-SEP-2001; Project End 31-JUL-2006 Summary: (adapted from the application) The paucity of therapeutic options for the treatment of chronic renal diseases results in the inexorable progression to end stage
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renal disease, characterized by interstitial fibrosis and glomerulosiderosis. In both processes, the myofibroblast has a central role as an effector cell elaborating excessive inflammatory mediators and extracellular matrix. In interstitial fibrosis, the degree of fibrosis and progression of renal disease directly correlates with the presence of myofibroblasts. Interstitial myofibroblasts arise mainly from tubular epithelial cells and fibroblasts. Factors implicated in the transformation include transforming growth factor (TGF)- beta1, endothelin- 1, and angiotensin ll- profibrogenic growth factors shown to stimulate gelatinase A production. In the glomerulus, gelatinase A transforms the mesangial cell into myofibroblasts. Similarly, gelatinase A is a key mediator of tubular epithelial cell- myofibroblast transdifferentiation in vitro. To locate the key regulatory elements for constitutive and growth factor- inducible gelatinase A transcription in the renal interstitium, a series of 5' flanking region deletion constructs of the rat gelatinase A gene will be transfected into normal rat kidney epithelial (NRK- 52e) and fibroblast (NRK- 49f) cells. The constructs extend to - 1686 bp of the immediate 5' flanking region and contain a laciferase reporter. Once the specific constitutive and growth factordependent enhancer sequences have been mapped, the specific interacting transcription factors will be characterized by the yeast one- hybrid system. A transgenic mouse model constitutively expressing activated gelatinase A will be constructed to directly test the relevance of gelatinase A on epithelial cell transdifferentiation to myofibroblasts and generation of interstitial fibrosis. To avoid a lethal phenotype, a tissue- specific, tetracycline- inducible transgenic system will be utilized. Using the mouse gammaglutamyl transpeptidase II promoter, the tetracycline transactivator protein (tTA) will be restricted to the proximal tubules. The tTA mouse will be crossed with a mouse harboring the gelatinase A gene under the control of a synthetic tetracycline operator (tet0). Only those cells with tTA (i.e. the proximal tubules) will be able to express activated gelatinase A. tTA, and consequently gelatinase A expression, is inhibited by doxycycline, so temporal control over activated gelatinase A expression will be maintained by doxycycline administration. To further evaluate gelatinase A's role in interstitial fibrosis, a gelatinase A knockout strain will be crossed with a TGF- beta1 transgenic strain. Since the TGF- beta1 transgenic mouse develops fibrosis, this crossing will evaluate gelatinase A as distal effector for TGF- beta1- induced fibrosis. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •
Project Title: THE ROLE OF KERATOCAN IN CORNEAL BIOLOGY Principal Investigator & Institution: Liu, Chia-Yang; Ophthalmology; University of Cincinnati 2624 Clifton Ave Cincinnati, Oh 45221 Timing: Fiscal Year 2002; Project Start 01-FEB-2001; Project End 31-OCT-2002 Summary: (adapted from the applicant's abstract): The long term objective of this application is to provide a better understanding of the role of keratocyte-specific keratan sulfate proteoglycan (KSPG), keratocan, in corneal function and the role of keratocan during development and in the maintenance of corneal homeostatis. Failure to have normal developmental process of the cornea will result in diseases such as corneal dystrophy. Keratocan (Ktcn), lumican (Lum), and mimecan belong to the small leucinerich proteoglycan (SLRP) gene family. They are major components of extracellular KSPG in vertebrate corneal stroma. It has been suggested that corneal KSPGs modulate collagen fibrillogenesis and thus contribute to the corneal transparency. The specific aim 1 is to test the hypothesis by generating Ktcn-null mice via gene-targeting and examining the phenotypic changes in Ktcn-/- cornea. The mouse Ktcn is specifically expressed in keratocytes. In embryos, the Ktcn expression tracks the neural crest cells migrating during morphogenesis of tissue such as corneal stroma, limb and diaphragm.
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We hypothesize that keratocyte lineage plays a pivotal role in corneal morphogenesis and in the maintenance of corneal function. The specific aim 2 is to elucidate the molecular basis of keratocyte-specific gene expression and to characterize keratocyte lineage. To achieve this goal, the investigator has shown that the 3.2 kb Ktcn can direct a foreign gene (beta-geo) expression specifically to keratocytes in adult transgenic mice (Tg). Aim 2.1 is to further define the keratocyte-specific cis-regulatory element within the 3.2 kb promoter by a series of Ktcn promoter deletion mutants using transgenic mice. Aim 2.2 is to confirm the cis-element with DNase I footprinting and electrophoretic mobility shift assay. The Ktcnpr3.2-betageobpA Tg allow us to trace keratocytes via X-gal staining. The specific aim 3 is to use this Tg as a model to study cellular responses of corneal keratocytes, conjunctival keratocytes, and scleral fibroblasts during wound healing. The specific aim 4 is to test the role of keratocytes during development and in the epithelium-mysenchyme interactions by genetic ablation of keratocytes in a tetracycline inducible Ktcnpr3.1-rtTA/tetO-DT-A Tg model. Aim 4.1 is to ablate the periocular neural crest cells during corneal morphogenesis and to examine the consequences on corneal and lens morphogenesis. Aim 4.2 is to ablate the keratocytes in adult animals, thus epithelium and endothelium response to the keratocyte cell death can be elucidated. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •
Project Title: THERAPEUTIC TARGETING OF BETA-CATENIN IN COLON CANCER Principal Investigator & Institution: Drebin, Jeffrey A.; Surgery; Washington University Lindell and Skinker Blvd St. Louis, Mo 63130 Timing: Fiscal Year 2003; Project Start 01-APR-2003; Project End 31-MAR-2007 Summary: (provided by applicant): Genetic deletions of the adenomatous polyposis coil (APC) tumor suppressor gene occur in the majority of colon cancers Loss of the APC gene products' ability to down-regulate the beta-catenin protein is hypothesized to represent a critical mechanism by which APC loss contributes to the etiology of colon cancer However, the APC protein interacts with multiple other proteins, including gamma-catenin and hDLG, that may play a role in neoplastic cell growth To date there has been little direct examination of the role of beta-catenin in the neoplastic behavior of human colon cancer cells The precise mechanisms by which beta-catenin signaling enhances the growth and survival of neoplastic cells are unknown, and the characterization of changes in gene expression resulting from beta-catenin-mediated transcriptional effects has been limited The overall goal of this project is to directly evaluate the role of beta-catenin on the neoplastic properties of APC-mutant intestinal neoplasms Antisense oligodeoxynucleotides capable of specifically suppressing betacatenin expression in human cancer cells have been identified The ability of the antibiotic doxycycline, at clinically achievable concentrations, to inhibit beta-catenin expression has also been elucidated These beta-catenin-suppressive agents will be used to define beta-catenin-dependent effects on cell cycle and apoptotic regulatory mechanisms in APC-mutant colon cancer cells Effects of beta- catenin on c-myc expression and function will be characterized Changes in gene expression profiles of APC-mutant colon cancer cells resulting from suppression of beta-catenin expression will be evaluated, and compared with changes induced by upstream alterations in APC or downstream alterations in Tcf4 activity Effects of suppressing beta-catenin on spontaneous adenoma formation will be evaluated using APC-mutant min mice and antitumor effects resulting from the in vivo suppression of beta-catenin expression will be evaluated in APC-mutant human colon cancer xenografts Collectively, these studies
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will define the role of beta-catenin in the neoplastic growth of APC-mutant colon cancer cells and will characterize the efficacy of chemopreventive and therapeutic strategies that target beta-catenin in vivo. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •
Project Title: TRANSGENIC MICE WITH PRECISE CONTROL OF GENE EXPRESSION Principal Investigator & Institution: Orosz, Charles G.; Professor; Surgery; Ohio State University 1960 Kenny Road Columbus, Oh 43210 Timing: Fiscal Year 2001; Project Start 15-AUG-1999; Project End 31-JUL-2004 Summary: This abstract is not available. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen
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Project Title: TRIAL OF ANTIBIOTICS TO REDUCE RECURRENT TRICHIASIS Principal Investigator & Institution: West, Sheila K.; Professor; Ophthalmology; Johns Hopkins University 3400 N Charles St Baltimore, Md 21218 Timing: Fiscal Year 2002; Project Start 01-SEP-2002; Project End 31-MAR-2005 Summary: Trachoma, caused by C. trachomatis, is the second leading cause of blindness worldwide, and control is a top priority of the blindness prevention community. In trachoma-endemic areas, 10% or more of adults have trichiasis, resulting from years of repeated infection, which is high risk for subsequent visual loss. Trichiasis can be corrected with surgery, but the recurrence rate at one year is disappointingly high, 17%, and it increases in subsequent years. There is strong evidence that ongoing exposure to infection with C. trachomatis, either from a persistent injection or exposure within families, drives ongoing scarring and trichiasis in these cases. The primary questions to be addressed by this investigation are: 1) Does post-surgical treatment of trichiasis cases with azithromycin reduce the one-year recurrence rate of trichiasis compared to standard care (topical tetracycline)? 2) Does post-surgical treatment of cases plus household members with azithromycin reduce the one-year recurrence rate of trichiasis compared to standard treatment? We propose a randomized, controlled clinical trial of 1425 adults with trichiasis scheduled for surgery in two health centers in the Lanfuro district of Ethiopia to address this questions. The three arm trial will have one arm in which cases receive a single dose of azithromycin post- surgery; a third arm in which cases will receive topical tetracycline post- surgery. Data on other risk factors will include baseline severity of trichiasis, surgery-related factors, and laboratory evidence and re- infection. Cases will be examined at 2 weeks and 2, 6, and 12 months postsurgery for recurrence of trichiasis. The results of this trial will have immediate public health impact by providing information for WHO recommendations for post-surgical treatment of trichiasis, as well as by guiding policy on azithromycin use for the 22 countries beginning National Trachoma Control programs worldwide. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen
E-Journals: PubMed Central3 PubMed Central (PMC) is a digital archive of life sciences journal literature developed and managed by the National Center for Biotechnology Information (NCBI) at the U.S. National 3
Adapted from the National Library of Medicine: http://www.pubmedcentral.nih.gov/about/intro.html.
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Library of Medicine (NLM).4 Access to this growing archive of e-journals is free and unrestricted.5 To search, go to http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=Pmc, and type “tetracycline” (or synonyms) into the search box. This search gives you access to full-text articles. The following is a sample of items found for tetracycline in the PubMed Central database: •
A conditional self-inactivating retrovirus vector that uses a tetracycline-responsive expression system. by Hwang JJ, Li L, Anderson WF.; 1997 Sep; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&rendertype=abstr act&artid=192013
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A GFP-equipped bidirectional expression module well suited for monitoring tetracycline-regulated gene expression in mouse. by Krestel HE, Mayford M, Seeburg PH, Sprengel R.; 2001 Apr 1; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=31300
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A Modified Tetracycline-Regulated System Provides Autoregulatory, Inducible Gene Expression in Cultured Cells and Transgenic Mice. by Shockett P, Difilippantonio M, Hellman N, Schatz DG.; 1995 Jul 3; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&rendertype=abstr act&artid=41550
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A multifunctional gene (tetR) controls Tn10-encoded tetracycline resistance. by Beck CF, Mutzel R, Barbe J, Muller W.; 1982 May; http://www.pubmedcentral.gov/picrender.fcgi?tool=pmcentrez&action=stream&blobt ype=pdf&artid=216410
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A new tetracycline resistance determinant, Tet H, from Pasteurella multocida specifying active efflux of tetracycline. by Hansen LM, McMurry LM, Levy SB, Hirsh DC.; 1993 Dec; http://www.pubmedcentral.gov/picrender.fcgi?tool=pmcentrez&action=stream&blobt ype=pdf&artid=192782
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A novel mechanism of action of tetracyclines: Effects on nitric oxide synthases. by Amin AR, Attur MG, Thakker GD, Patel PD, Vyas PR, Patel RN, Patel IR, Abramson SB.; 1996 Nov 26; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=19486
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A novel tetracycline-dependent expression vector with low basal expression and potent regulatory properties in various mammalian cell lines. by Hoffmann A, Villalba M, Journot L, Spengler D.; 1997 Mar 1; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&rendertype=abstr act&artid=146524
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A novel tetracycline-dependent transactivator with E2F4 transcriptional activation domain. by Akagi K, Kanai M, Saya H, Kozu T, Berns A.; 2001 Feb 15; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=29630
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With PubMed Central, NCBI is taking the lead in preservation and maintenance of open access to electronic literature, just as NLM has done for decades with printed biomedical literature. PubMed Central aims to become a world-class library of the digital age. 5 The value of PubMed Central, in addition to its role as an archive, lies in the availability of data from diverse sources stored in a common format in a single repository. Many journals already have online publishing operations, and there is a growing tendency to publish material online only, to the exclusion of print.
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A site-specific DNA inversion in Bacteroides plasmid pBF4 is influenced by the presence of the conjugal tetracycline resistance element. by Matthews BG, Roudier C, Guiney DG.; 1991 Aug; http://www.pubmedcentral.gov/picrender.fcgi?tool=pmcentrez&action=stream&blobt ype=pdf&artid=208220
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A tetracycline derivative, minocycline, reduces inflammation and protects against focal cerebral ischemia with a wide therapeutic window. by Yrjanheikki J, Tikka T, Keinanen R, Goldsteins G, Chan PH, Koistinaho J.; 1999 Nov 9; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=23976
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A tetracycline efflux gene on Bacteroides transposon Tn4400 does not contribute to tetracycline resistance. by Speer BS, Salyers AA.; 1990 Jan; http://www.pubmedcentral.gov/picrender.fcgi?tool=pmcentrez&action=stream&blobt ype=pdf&artid=208431
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A Tn10 derivative (T-POP) for isolation of insertions with conditional (tetracyclinedependent) phenotypes. by Rappleye CA, Roth JR.; 1997 Sep; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&rendertype=abstr act&artid=179473
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Accumulation of Tetracyclines by Escherichia coli. by De Zeeuw JR.; 1968 Feb; http://www.pubmedcentral.gov/picrender.fcgi?tool=pmcentrez&action=stream&blobt ype=pdf&artid=252046
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Active uptake of tetracycline by membrane vesicles from susceptible Escherichia coli. by McMurry LM, Cullinane JC, Petrucci RE Jr, Levy SB.; 1981 Sep; http://www.pubmedcentral.gov/picrender.fcgi?tool=pmcentrez&action=stream&blobt ype=pdf&artid=181692
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Activities of the glycylcyclines N,N-dimethylglycylamido-minocycline and N,Ndimethylglycylamido-6-demethyl-6-deoxytetracycline against Nocardia spp. and tetracycline-resistant isolates of rapidly growing mycobacteria. by Brown BA, Wallace RJ Jr, Onyi G.; 1996 Apr; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&rendertype=abstr act&artid=163222
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Amplifiable resistance to tetracycline, chloramphenicol, and other antibiotics in Escherichia coli: involvement of a non-plasmid-determined efflux of tetracycline. by George AM, Levy SB.; 1983 Aug; http://www.pubmedcentral.gov/picrender.fcgi?tool=pmcentrez&action=stream&blobt ype=pdf&artid=217720
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Amplification of the Tetracycline Resistance Determinant of pAM[alpha]1 in Enterococcus faecalis Requires a Site-Specific Recombination Event Involving Relaxase. by Francia MV, Clewell DB.; 2002 Sep; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=135321
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An activator/repressor dual system allows tight tetracycline-regulated gene expression in budding yeast. by Belli G, Gari E, Piedrafita L, Aldea M, Herrero E.; 1998 Feb 15; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&rendertype=abstr act&artid=147371
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An episomal vector for stable tetracycline-regulated gene expression. by Jost M, Kari C, Rodeck U.; 1997 Aug 1; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&rendertype=abstr act&artid=146851
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An IS257-Derived Hybrid Promoter Directs Transcription of a tetA(K) Tetracycline Resistance Gene in the Staphylococcus aureus Chromosomal mec Region. by Simpson AE, Skurray RA, Firth N.; 2000 Jun 15; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=101884
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An occurrence of a noticeable alternating pyrimidine-purine run in the replication origins of tetracycline-resistance plasmids pNSI and pT181. by Shishido K.; 1988 Feb 25; http://www.pubmedcentral.gov/picrender.fcgi?tool=pmcentrez&action=stream&blobt ype=pdf&artid=336360
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Analysis of tetracycline resistance encoded by transposon Tn10: deletion mapping of tetracycline-sensitive point mutations and identification of two structural genes. by Coleman DC, Chopra I, Shales SW, Howe TG, Foster TJ.; 1983 Feb; http://www.pubmedcentral.gov/picrender.fcgi?tool=pmcentrez&action=stream&blobt ype=pdf&artid=221715
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Anhydrotetracycline, a novel effector for tetracycline controlled gene expression systems in eukaryotic cells. by Gossen M, Bujard H.; 1993 Sep 11; http://www.pubmedcentral.gov/picrender.fcgi?tool=pmcentrez&action=stream&blobt ype=pdf&artid=310095
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Antioxidant Functions Required for Insusceptibility of Saccharomyces cerevisiae to Tetracycline Antibiotics. by Angrave FE, Avery SV.; 2001 Oct; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=90759
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Bacterial resistance to tetracycline: mechanisms, transfer, and clinical significance. by Speer BS, Shoemaker NB, Salyers AA.; 1992 Oct; http://www.pubmedcentral.gov/picrender.fcgi?tool=pmcentrez&action=stream&blobt ype=pdf&artid=358256
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Bi-directional gene switching with the tetracycline repressor and a novel tetracycline antagonist. by Chrast-Balz J, Hooft van Huijsduijnen R.; 1996 Aug 1; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&rendertype=abstr act&artid=146027
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Cetocycline, Tetracycline Analog: In Vitro Studies of Antimicrobial Activity, Serum Binding, Lipid Solubility, and Uptake by Bacteria. by Proctor R, Craig W, Kunin C.; 1978 Apr; http://www.pubmedcentral.gov/picrender.fcgi?tool=pmcentrez&action=stream&blobt ype=pdf&artid=352294
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Changes in the prevalence of resistant Escherichia coli in cattle receiving subcutaneously injectable oxytetracycline in addition to in-feed chlortetracycline compared with cattle receiving only in-feed chlortetracycline. by O'Connor AM, Poppe C, McEwen SA.; 2002 Jul; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=226997
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Characteristics of murine model of genital infection with Chlamydia trachomatis and effects of therapy with tetracyclines, amoxicillin-clavulanic acid, or azithromycin. by Beale AS, Upshon PA.; 1994 Sep; http://www.pubmedcentral.gov/picrender.fcgi?tool=pmcentrez&action=stream&blobt ype=pdf&artid=284665
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Characterization and expression of a cloned tetracycline resistance determinant from Campylobacter jejuni plasmid pUA466. by Taylor DE, Hiratsuka K, Ray H, Manavathu EK.; 1987 Jul; http://www.pubmedcentral.gov/picrender.fcgi?tool=pmcentrez&action=stream&blobt ype=pdf&artid=212337
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Characterization and expression of a cloned tetracycline resistance determinant from the chromosome of Streptococcus mutans. by Tobian JA, Cline ML, Macrina FL.; 1984 Nov; http://www.pubmedcentral.gov/picrender.fcgi?tool=pmcentrez&action=stream&blobt ype=pdf&artid=214770
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Characterization and mapping of regions encoding clindamycin resistance, tetracycline resistance, and a replication function on the Bacteroides R plasmid pCP1. by Matthews BG, Guiney DG.; 1986 Aug; http://www.pubmedcentral.gov/picrender.fcgi?tool=pmcentrez&action=stream&blobt ype=pdf&artid=212919
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Characterization of a novel tetracycline resistance that functions only in aerobically grown Escherichia coli. by Speer BS, Salyers AA.; 1988 Apr; http://www.pubmedcentral.gov/picrender.fcgi?tool=pmcentrez&action=stream&blobt ype=pdf&artid=210984
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Characterization of restriction endonuclease activities in tetracycline producing strains of Streptomyces aureofaciens. by Pristas P, Godany A, Sevcikova B, Oktavcova B, Farkasovska J.; 1992 Aug 25; http://www.pubmedcentral.gov/picrender.fcgi?tool=pmcentrez&action=stream&blobt ype=pdf&artid=334149
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Characterization of two tetracycline resistance determinants in Streptococcus faecalis JH1. by LeBlanc DJ, Lee LN.; 1982 May; http://www.pubmedcentral.gov/picrender.fcgi?tool=pmcentrez&action=stream&blobt ype=pdf&artid=216436
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Cloning and Characterization of a Tetracycline Resistance Determinant Present in Agrobacterium tumefaciens C58. by Luo ZQ, Farrand SK.; 1999 Jan 15; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=93418
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Comparative assessment of Etest for testing susceptibilities of Neisseria gonorrhoeae to penicillin, tetracycline, ceftriaxone, cefotaxime, and ciprofloxacin: investigation using 510(k) review criteria, recommended by the Food and Drug Administration. by Biedenbach DJ, Jones RN.; 1996 Dec; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&rendertype=abstr act&artid=229487
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Comparative trial of rifampin-doxycycline versus tetracycline-streptomycin in the therapy of human brucellosis. by Ariza J, Gudiol F, Pallares R, Rufi G, FernandezViladrich P.; 1985 Oct; http://www.pubmedcentral.gov/picrender.fcgi?tool=pmcentrez&action=stream&blobt ype=pdf&artid=180303
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Comparison of kinetics of active tetracycline uptake and active tetracycline efflux in sensitive and plasmid RP4-containing Pseudomonas putida. by Hedstrom RC, Crider BP, Eagon RG.; 1982 Oct; http://www.pubmedcentral.gov/picrender.fcgi?tool=pmcentrez&action=stream&blobt ype=pdf&artid=221399
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Comparison of single-dose tetracycline hydrochloride to conventional therapy of urinary tract infections. by Rosenstock J, Smith LP, Gurney M, Lee K, Weinberg WG, Longfield JN, Tauber WB, Karney WW.; 1985 Apr; http://www.pubmedcentral.gov/picrender.fcgi?tool=pmcentrez&action=stream&blobt ype=pdf&artid=180116
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Comparison of the in vitro activities of fenticonazole, other imidazoles, metronidazole, and tetracycline against organisms associated with bacterial vaginosis and skin infections. by Jones BM, Geary I, Lee ME, Duerden BI.; 1989 Jun; http://www.pubmedcentral.gov/picrender.fcgi?tool=pmcentrez&action=stream&blobt ype=pdf&artid=284267
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Comparison of the In Vitro Activity of the Glycylcycline Tigecycline (Formerly GAR936) with Those of Tetracycline, Minocycline, and Doxycycline against Isolates of Nontuberculous Mycobacteria. by Wallace, Jr. RJ, Brown-Elliott BA, Crist CJ, Mann L, Wilson RW.; 2002 Oct; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=128779
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Conditional cell ablation by stringent tetracycline-dependent regulation of barnase in mammalian cells. by Leuchtenberger S, Perz A, Gatz C, Bartsch JW.; 2001 Aug 15; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=55860
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Conditional gene expression by controlling translation with tetracycline-binding aptamers. by Suess B, Hanson S, Berens C, Fink B, Schroeder R, Hillen W.; 2003 Apr 1; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=152801
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Conditional Transformation of a Pancreatic [beta]-Cell Line Derived from Transgenic Mice Expressing a Tetracycline-Regulated Oncogene. by Efrat S, Fusco-DeMane D, Lemberg H, Emran OA, Wang X.; 1995 Apr 11; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&rendertype=abstr act&artid=42210
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Constitutive expression of tetracycline resistance mediated by a Tn10-like element in Haemophilus parainfluenzae results from a mutation in the repressor gene. by Heuer C, Hickman RK, Curiale MS, Hillen W, Levy SB.; 1987 Mar; http://www.pubmedcentral.gov/picrender.fcgi?tool=pmcentrez&action=stream&blobt ype=pdf&artid=211891
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Construction of a single-copy promoter vector and its use in analysis of regulation of the transposon Tn10 tetracycline resistance determinant. by Bertrand KP, Postle K, Wray LV Jr, Reznikoff WS.; 1984 Jun; http://www.pubmedcentral.gov/picrender.fcgi?tool=pmcentrez&action=stream&blobt ype=pdf&artid=215528
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Co-regulation of two gene activities by tetracycline via a bidirectional promoter. by Baron U, Freundlieb S, Gossen M, Bujard H.; 1995 Sep 11; http://www.pubmedcentral.gov/picrender.fcgi?tool=pmcentrez&action=stream&blobt ype=pdf&artid=307245
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Cross-resistance to fluoroquinolones in multiple-antibiotic-resistant (Mar) Escherichia coli selected by tetracycline or chloramphenicol: decreased drug
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accumulation associated with membrane changes in addition to OmpF reduction. by Cohen SP, McMurry LM, Hooper DC, Wolfson JS, Levy SB.; 1989 Aug; http://www.pubmedcentral.gov/picrender.fcgi?tool=pmcentrez&action=stream&blobt ype=pdf&artid=172647 •
Cryptic tetracycline resistance determinant (class F) from Bacteroides fragilis mediates resistance in Escherichia coli by actively reducing tetracycline accumulation. by Park BH, Hendricks M, Malamy MH, Tally FP, Levy SB.; 1987 Nov; http://www.pubmedcentral.gov/picrender.fcgi?tool=pmcentrez&action=stream&blobt ype=pdf&artid=175031
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Crystal structures of complexes of the small ribosomal subunit with tetracycline, edeine and IF3. by Pioletti M, Schlunzen F, Harms J, Zarivach R, Gluhmann M, Avila H, Bashan A, Bartels H, Auerbach T, Jacobi C, Hartsch T, Yonath A, Franceschi F.; 2001 Apr 17; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=125237
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Cytotoxic and enterotoxic activities of Campylobacter jejuni are not specified by tetracycline resistance plasmids pMAK175 and pUA466. by Taylor DE, Johnson WM, Lior H.; 1987 Jan; http://www.pubmedcentral.gov/picrender.fcgi?tool=pmcentrez&action=stream&blobt ype=pdf&artid=265844
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Decreased function of the class B tetracycline efflux protein Tet with mutations at aspartate 15, a putative intramembrane residue. by McMurry LM, Stephan M, Levy SB.; 1992 Oct; http://www.pubmedcentral.gov/picrender.fcgi?tool=pmcentrez&action=stream&blobt ype=pdf&artid=207700
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Delta pH-dependent accumulation of tetracycline in Escherichia coli. by Yamaguchi A, Ohmori H, Kaneko-Ohdera M, Nomura T, Sawai T.; 1991 Jan; http://www.pubmedcentral.gov/picrender.fcgi?tool=pmcentrez&action=stream&blobt ype=pdf&artid=244940
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Detection of Oxytetracycline Production by Streptomyces rimosus in Soil Microcosms by Combining Whole-Cell Biosensors and Flow Cytometry. by Hansen LH, Ferrari B, Sorensen AH, Veal D, Sorensen SJ.; 2001 Jan; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=92555
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Detection of tetracyclines and efflux pump inhibitors. by Rothstein DM, McGlynn M, Bernan V, McGahren J, Zaccardi J, Cekleniak N, Bertrand KP.; 1993 Aug; http://www.pubmedcentral.gov/picrender.fcgi?tool=pmcentrez&action=stream&blobt ype=pdf&artid=188031
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Development, Validation, and Application of PCR Primers for Detection of Tetracycline Efflux Genes of Gram-Negative Bacteria. by Aminov RI, Chee-Sanford JC, Garrigues N, Teferedegne B, Krapac IJ, White BA, Mackie RI.; 2002 Apr; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=123860
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Disseminated tetracycline resistance in oral streptococci: implication of a conjugative transposon. by Hartley DL, Jones KR, Tobian JA, LeBlanc DJ, Macrina FL.; 1984 Jul; http://www.pubmedcentral.gov/picrender.fcgi?tool=pmcentrez&action=stream&blobt ype=pdf&artid=263248
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Dissemination of the tetM tetracycline resistance determinant to Ureaplasma urealyticum. by Roberts MC, Kenny GE.; 1986 Feb; http://www.pubmedcentral.gov/picrender.fcgi?tool=pmcentrez&action=stream&blobt ype=pdf&artid=176409
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Diverse Strategies for Tetracycline-Regulated Inducible Gene Expression. by Shockett PE, Schatz DG.; 1996 May 28; http://www.pubmedcentral.gov/picrender.fcgi?tool=pmcentrez&action=stream&blobt ype=pdf&artid=39217
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Does a tetracycline resistance determinant of class N exist? by Horaud T, Delbos F, Pepper K.; 1990 Jul; http://www.pubmedcentral.gov/picrender.fcgi?tool=pmcentrez&action=stream&blobt ype=pdf&artid=175999
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Effect of mutational alteration of Asn-128 in the putative GTP-binding domain of tetracycline resistance determinant Tet(O) from Campylobacter jejuni. by Grewal J, Manavathu EK, Taylor DE.; 1993 Dec; http://www.pubmedcentral.gov/picrender.fcgi?tool=pmcentrez&action=stream&blobt ype=pdf&artid=192766
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Effects of Metronidazole, Tetracycline, and Bismuth-Metronidazole-Tetracycline Triple Therapy in the Helicobacter pylori SS1 Mouse Model after 1 Day of Dosing: Development of an H. pylori Lead Selection Model. by Sizemore CF, Quispe JD, Amsler KM, Modzelewski TC, Merrill JJ, Stevenson DA, Foster LA, Slee AM.; 2002 May; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=127199
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Effects of tetracycline on the streptococcal flora of periodontal pockets. by Hawley RJ, Lee LN, LeBlanc DJ.; 1980 Mar; http://www.pubmedcentral.gov/picrender.fcgi?tool=pmcentrez&action=stream&blobt ype=pdf&artid=283793
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Effects of toluene permeabilization and cell deenergization on tetracycline resistance in Escherichia coli. by McMurry LM, Hendricks M, Levy SB.; 1986 Apr; http://www.pubmedcentral.gov/picrender.fcgi?tool=pmcentrez&action=stream&blobt ype=pdf&artid=180466
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Efficacy of chloramphenicol, enrofloxacin, and tetracycline for treatment of experimental Rocky Mountain spotted fever in dogs. by Breitschwerdt EB, Davidson MG, Aucoin DP, Levy MG, Szabados NS, Hegarty BC, Kuehne AL, James RL.; 1991 Nov; http://www.pubmedcentral.gov/picrender.fcgi?tool=pmcentrez&action=stream&blobt ype=pdf&artid=245388
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Elucidating the Essential Role of the A14 Phosphoprotein in Vaccinia Virus Morphogenesis: Construction and Characterization of a Tetracycline-Inducible Recombinant. by Traktman P, Liu K, DeMasi J, Rollins R, Jesty S, Unger B.; 2000 Apr 15; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=111878
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Energetics of tetracycline transport into Escherichia coli. by Smith MC, Chopra I.; 1984 Apr; http://www.pubmedcentral.gov/picrender.fcgi?tool=pmcentrez&action=stream&blobt ype=pdf&artid=185549
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Enhanced antiparasitic activity of lipophilic tetracyclines: role of uptake. by Katiyar SK, Edlind TD.; 1991 Nov; http://www.pubmedcentral.gov/picrender.fcgi?tool=pmcentrez&action=stream&blobt ype=pdf&artid=245359
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Enhanced immune responses in mice treated with penicillin-tetracycline or trimethoprim-sulfamethoxazole when colonized intragastrically with Candida albicans. by Domer JE, Hector RF.; 1987 May; http://www.pubmedcentral.gov/picrender.fcgi?tool=pmcentrez&action=stream&blobt ype=pdf&artid=174816
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Enhancement of the in vitro activity of amphotericin B against Aspergillus spp. by tetracycline analogs. by Hughes CE, Harris C, Peterson LR, Gerding DN.; 1984 Dec; http://www.pubmedcentral.gov/picrender.fcgi?tool=pmcentrez&action=stream&blobt ype=pdf&artid=180035
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Epstein-Barr Virus (EBV) Nuclear Protein 2-Induced Disruption of EBV Latency in the Burkitt's Lymphoma Cell Line Akata: Analysis by Tetracycline-Regulated Expression. by Fujiwara S, Nitadori Y, Nakamura H, Nagaishi T, Ono Y.; 1999 Jun; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=112573
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Etiology of Tetracycline-Associated Pseudomembranous Colitis in Hamsters. by Toshniwal R, Fekety R, Silva J Jr.; 1979 Aug; http://www.pubmedcentral.gov/picrender.fcgi?tool=pmcentrez&action=stream&blobt ype=pdf&artid=352815
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Evaluation of a Tetracycline-Inducible Promoter in Staphylococcus aureus In Vitro and In Vivo and Its Application in Demonstrating the Role of sigB in Microcolony Formation. by Bateman BT, Donegan NP, Jarry TM, Palma M, Cheung AL.; 2001 Dec; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=98881
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Evidence that tetracycline analogs whose primary target is not the bacterial ribosome cause lysis of Escherichia coli. by Oliva B, Gordon G, McNicholas P, Ellestad G, Chopra I.; 1992 May; http://www.pubmedcentral.gov/picrender.fcgi?tool=pmcentrez&action=stream&blobt ype=pdf&artid=188751
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Exploring the sequence space for tetracycline-dependent transcriptional activators: Novel mutations yield expanded range and sensitivity. by Urlinger S, Baron U, Thellmann M, Hasan MT, Bujard H, Hillen W.; 2000 Jul 5; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=16653
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Facilitated transfer of IncP beta R751 derivatives from the chromosome of Bacteroides uniformis to Escherichia coli recipients by a conjugative Bacteroides tetracycline resistance element. by Shoemaker NB, Salyers AA.; 1987 Jul; http://www.pubmedcentral.gov/picrender.fcgi?tool=pmcentrez&action=stream&blobt ype=pdf&artid=212365
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Fe2 +-Tetracycline-Mediated Cleavage of the Tn10 Tetracycline Efflux Protein TetA Reveals a Substrate Binding Site near Glutamine 225 in Transmembrane Helix 7. by McMurry LM, Aldema-Ramos ML, Levy SB.; 2002 Sep; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=135328
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Frequency of four classes of tetracycline resistance determinants in Salmonella and Shigella spp. clinical isolates. by Martinez-Salazar JM, Alvarez G, Gomez-Eichelmann MC.; 1986 Oct; http://www.pubmedcentral.gov/picrender.fcgi?tool=pmcentrez&action=stream&blobt ype=pdf&artid=176499
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Functional Importance and Local Environments of the Cysteines in the Tetracycline Resistance Protein Encoded by Plasmid pBR322. by Jewell JE, Orwick J, Liu J, Miller KW.; 1999 Mar 1; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=93563
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Gene heterogeneity for tetracycline resistance in Staphylococcus spp. by Bismuth R, Zilhao R, Sakamoto H, Guesdon JL, Courvalin P.; 1990 Aug; http://www.pubmedcentral.gov/picrender.fcgi?tool=pmcentrez&action=stream&blobt ype=pdf&artid=171885
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Gene in the major cotransduction gap of the Escherichia coli K-12 linkage map required for the expression of chromosomal resistance to tetracycline and other antibiotics. by George AM, Levy SB.; 1983 Aug; http://www.pubmedcentral.gov/picrender.fcgi?tool=pmcentrez&action=stream&blobt ype=pdf&artid=217721
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Generation of Packaging Cell Lines for Pseudotyped Retroviral Vectors of the G Protein of Vesicular Stomatitis Virus by Using a Modified Tetracycline Inducible System. by Chen S, Iida A, Guo L, Friedmann T, Yee J.; 1996 Sep 17; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&rendertype=abstr act&artid=38335
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Genetic Determinants of Tetracycline Resistance in Vibrio harveyi. by Teo JW, Tan TM, Poh CL.; 2002 Apr; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=127092
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Global Changes in Kaposi's Sarcoma-Associated Virus Gene Expression Patterns following Expression of a Tetracycline-Inducible Rta Transactivator. by Nakamura H, Lu M, Gwack Y, Souvlis J, Zeichner SL, Jung JU.; 2003 Apr; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=150665
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Glutamate residues located within putative transmembrane helices are essential for TetA(P)-mediated tetracycline efflux. by Kennan RM, McMurry LM, Levy SB, Rood JI.; 1997 Nov; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&rendertype=abstr act&artid=179641
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Growth and Development of Tetracycline-Resistant Chlamydia suis. by Lenart J, Andersen AA, Rockey DD.; 2001 Aug; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=90631
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Heterogeneity of tetracycline resistance determinants in Streptococcus. by Burdett V, Inamine J, Rajagopalan S.; 1982 Mar; http://www.pubmedcentral.gov/picrender.fcgi?tool=pmcentrez&action=stream&blobt ype=pdf&artid=216488
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Heterologous repressor-operator recognition among four classes of tetracycline resistance determinants. by Klock G, Unger B, Gatz C, Hillen W, Altenbuchner J, Schmid K, Schmitt R.; 1985 Jan; http://www.pubmedcentral.gov/picrender.fcgi?tool=pmcentrez&action=stream&blobt ype=pdf&artid=214875
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High Rate of Tetracycline Resistance in Streptococcus pyogenes in Iran: an Epidemiological Study. by Jasir A, Tanna A, Noorani A, Mirsalehian A, Efstratiou A, Schalen C.; 2000 Jun; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=86737
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High-level tetracycline resistance in Neisseria gonorrhoeae is result of acquisition of streptococcal tetM determinant. by Morse SA, Johnson SR, Biddle JW, Roberts MC.; 1986 Nov; http://www.pubmedcentral.gov/picrender.fcgi?tool=pmcentrez&action=stream&blobt ype=pdf&artid=176510
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High-level tetracycline resistance resulting from TetM in strains of Neisseria spp., Kingella denitrificans, and Eikenella corrodens. by Knapp JS, Johnson SR, Zenilman JM, Roberts MC, Morse SA.; 1988 May; http://www.pubmedcentral.gov/picrender.fcgi?tool=pmcentrez&action=stream&blobt ype=pdf&artid=172269
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Homology of a transferable tetracycline resistance determinant of Clostridium difficile with Streptococcus (Enterococcus) faecalis transposon Tn916. by Hachler H, Kayser FH, Berger-Bachi B.; 1987 Jul; http://www.pubmedcentral.gov/picrender.fcgi?tool=pmcentrez&action=stream&blobt ype=pdf&artid=174867
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Identification and cloning of a tetracycline resistance gene from the fish pathogen Vibrio salmonicida. by Sorum H, Roberts MC, Crosa JH.; 1992 Mar; http://www.pubmedcentral.gov/picrender.fcgi?tool=pmcentrez&action=stream&blobt ype=pdf&artid=190565
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In Vitro Activities of a New Ketolide, ABT-773, Alone and in Combination with Amoxicillin, Metronidazole, or Tetracycline against Helicobacter pylori. by Pendland SL, Prause JL, Neuhauser MM, Boyea N, Hackleman JM, Danziger LH.; 2000 Sep; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=90095
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In vitro activities of azithromycin, clarithromycin, erythromycin, and tetracycline against 13 strains of Chlamydia pneumoniae. by Welsh L, Gaydos C, Quinn TC.; 1996 Jan; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&rendertype=abstr act&artid=163084
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In vitro activities of lomefloxacin, tetracycline, penicillin, spectinomycin, and ceftriaxone against Neisseria gonorrhoeae and Chlamydia trachomatis. by Talbot H, Romanowski B.; 1989 Dec; http://www.pubmedcentral.gov/picrender.fcgi?tool=pmcentrez&action=stream&blobt ype=pdf&artid=172820
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In vitro activities of two new glycylcyclines, N,N-dimethylglycylamido derivatives of minocycline and 6-demethyl-6-deoxytetracycline, against 339 strains of anaerobic bacteria. by Wexler HM, Molitoris E, Finegold SM.; 1994 Oct; http://www.pubmedcentral.gov/picrender.fcgi?tool=pmcentrez&action=stream&blobt ype=pdf&artid=284777
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In vitro and in vivo antibacterial activities of the glycylcyclines, a new class of semisynthetic tetracyclines. by Testa RT, Petersen PJ, Jacobus NV, Sum PE, Lee VJ, Tally FP.; 1993 Nov; http://www.pubmedcentral.gov/picrender.fcgi?tool=pmcentrez&action=stream&blobt ype=pdf&artid=192378
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In vitro evaluation of activities of azithromycin, erythromycin, and tetracycline against Chlamydia trachomatis and Chlamydia pneumoniae. by Welsh LE, Gaydos CA, Quinn TC.; 1992 Feb; http://www.pubmedcentral.gov/picrender.fcgi?tool=pmcentrez&action=stream&blobt ype=pdf&artid=188358
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In vitro evaluation of CP-62,993, erythromycin, clindamycin, and tetracycline against Chlamydia trachomatis. by Walsh M, Kappus EW, Quinn TC.; 1987 May; http://www.pubmedcentral.gov/picrender.fcgi?tool=pmcentrez&action=stream&blobt ype=pdf&artid=174839
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Increase in resistance of Mycoplasma hominis to tetracyclines. by Cummings MC, McCormack WM.; 1990 Dec; http://www.pubmedcentral.gov/picrender.fcgi?tool=pmcentrez&action=stream&blobt ype=pdf&artid=172049
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Inducible gene expression by retrovirus-mediated transfer of a modified tetracyclineregulated system. by Iida A, Chen ST, Friedmann T, Yee JK.; 1996 Sep; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&rendertype=abstr act&artid=190626
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Inducible Overexpression of a Toxic Protein by an Adenovirus Vector with a Tetracycline-Regulatable Expression Cassette. by Massie B, Couture F, Lamoureux L, Mosser DD, Guilbault C, Jolicoeur P, Belanger F, Langelier Y.; 1998 Mar; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=109527
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Induction of chloramphenicol and tetracycline resistance in Flexibacter sp. strain FS1. by Barcak GJ, Burchard RP.; 1985 Feb; http://www.pubmedcentral.gov/picrender.fcgi?tool=pmcentrez&action=stream&blobt ype=pdf&artid=214963
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Influence of Magnesium and Manganese on Some Biological and Physical Properties of Tetracycline. by Sompolinsky D, Samra Z.; 1972 May; http://www.pubmedcentral.gov/picrender.fcgi?tool=pmcentrez&action=stream&blobt ype=pdf&artid=247437
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Influence of tetracyclines on human polymorphonuclear leukocyte function. by Glette J, Sandberg S, Hopen G, Solberg CO.; 1984 Mar; http://www.pubmedcentral.gov/picrender.fcgi?tool=pmcentrez&action=stream&blobt ype=pdf&artid=185516
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Inhibition of beta-galactosidase biosynthesis in Escherichia coli by tetracycline residues in milk. by D'Haese E, Nelis HJ, Reybroeck W.; 1997 Oct; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&rendertype=abstr act&artid=168727
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Inhibition of protein synthesis occurring on tetracycline-resistant, TetM-protected ribosomes by a novel class of tetracyclines, the glycylcyclines. by Rasmussen BA, Gluzman Y, Tally FP.; 1994 Jul; http://www.pubmedcentral.gov/picrender.fcgi?tool=pmcentrez&action=stream&blobt ype=pdf&artid=284611
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Inhibition of Trypsin-Like Cysteine Proteinases (Gingipains) from Porphyromonas gingivalis by Tetracycline and Its Analogues. by Imamura T, Matsushita K, Travis J, Potempa J.; 2001 Oct; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=90745
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Interaction of imipenem with erythromycin and tetracycline assessed by microdilution checkerboard techniques. by Gould IM, Wilson D, Milne K, Paterson A, Golder D, Russell D.; 1991 Nov; http://www.pubmedcentral.gov/picrender.fcgi?tool=pmcentrez&action=stream&blobt ype=pdf&artid=245393
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Interaction of tetracycline with RNA: photoincorporation into ribosomal RNA of Escherichia coli. by Oehler R, Polacek N, Steiner G, Barta A.; 1997 Mar 15; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&rendertype=abstr act&artid=146554
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Intracistronic complementation of the tetracycline resistance membrane protein of Tn10. by Curiale MS, McMurry LM, Levy SB.; 1984 Jan; http://www.pubmedcentral.gov/picrender.fcgi?tool=pmcentrez&action=stream&blobt ype=pdf&artid=215154
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Intraperitoneal injection of tetracyclines protects mice from lethal endotoxemia downregulating inducible nitric oxide synthase in various organs and cytokine and nitrate secretion in blood. by Milano S, Arcoleo F, D'Agostino P, Cillari E.; 1997 Jan; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&rendertype=abstr act&artid=163671
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Isolation and Characterization of Tetracycline-Resistant Clinical Isolates of Helicobacter pylori. by Kwon DH, Kim JJ, Lee M, Yamaoka Y, Kato M, Osato MS, ElZaatari FA, Graham DY.; 2000 Nov; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=101634
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Isolation of Tetracycline-Resistant Megasphaera elsdenii Strains with Novel Mosaic Gene Combinations of tet(O) and tet(W) from Swine. by Stanton TB, Humphrey SB.; 2003 Jul; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=165211
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Kinetic analysis of tetracycline accumulation by Streptococcus faecalis. by Lindley EV, Munske GR, Magnuson JA.; 1984 Apr; http://www.pubmedcentral.gov/picrender.fcgi?tool=pmcentrez&action=stream&blobt ype=pdf&artid=215418
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Lack of an Immune Response against the Tetracycline-Dependent Transactivator Correlates with Long-Term Doxycycline-Regulated Transgene Expression in Nonhuman Primates after Intramuscular Injection of Recombinant Adeno-Associated Virus. by Favre D, Blouin V, Provost N, Spisek R, Porrot F, Bohl D, Marme F, Cherel Y, Salvetti A, Hurtrel B, Heard JM, Riviere Y, Moullier P.; 2002 Nov; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=136781
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Lack of evidence for a saturable tetracycline transport system in Staphylococcus aureus. by Chopra I, Ismail S, Oliva B.; 1991 Dec; http://www.pubmedcentral.gov/picrender.fcgi?tool=pmcentrez&action=stream&blobt ype=pdf&artid=245447
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Light-induced, carrier-mediated transport of tetracycline by Rhodopseudomonas sphaeroides. by Weckesser J, Magnuson JA.; 1979 Jun; http://www.pubmedcentral.gov/picrender.fcgi?tool=pmcentrez&action=stream&blobt ype=pdf&artid=218090
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Limitations of a fluorescence assay for studies on tetracycline transport into Escherichia coli. by Smith MC, Chopra I.; 1983 Jan; http://www.pubmedcentral.gov/picrender.fcgi?tool=pmcentrez&action=stream&blobt ype=pdf&artid=184639
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Macrolide and Tetracycline Resistance and Molecular Relationships of Clinical Strains of Streptococcus agalactiae. by Culebras E, Rodriguez-Avial I, Betriu C, Redondo M, Picazo JJ.; 2002 May; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=127186
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Mechanism of Tet(O)-mediated tetracycline resistance. by Connell SR, Trieber CA, Dinos GP, Einfeldt E, Taylor DE, Nierhaus KH.; 2003 Feb 17; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=145453
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Modulation of myosin A expression by a newly established tetracycline repressorbased inducible system in Toxoplasma gondii. by Meissner M, Brecht S, Bujard H, Soldati D.; 2001 Nov 15; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=92585
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Molecular analysis of transferable tetracycline resistance plasmids from Clostridium perfringens. by Abraham LJ, Rood JI.; 1985 Feb; http://www.pubmedcentral.gov/picrender.fcgi?tool=pmcentrez&action=stream&blobt ype=pdf&artid=214930
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Molecular basis of tetracycline action: identification of analogs whose primary target is not the bacterial ribosome. by Rasmussen B, Noller HF, Daubresse G, Oliva B, Misulovin Z, Rothstein DM, Ellestad GA, Gluzman Y, Tally FP, Chopra I.; 1991 Nov; http://www.pubmedcentral.gov/picrender.fcgi?tool=pmcentrez&action=stream&blobt ype=pdf&artid=245376
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Molecular Cloning and Functional Analysis of a Novel Tetracycline Resistance Determinant, tet(V), from Mycobacterium smegmatis. by De Rossi E, Blokpoel MC, Cantoni R, Branzoni M, Riccardi G, Young DB, De Smet KA, Ciferri O.; 1998 Aug; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=105712
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Molecular cloning of tetracycline resistance genes from Streptomyces rimosus in Streptomyces griseus and characterization of the cloned genes. by Ohnuki T, Katoh T, Imanaka T, Aiba S.; 1985 Mar; http://www.pubmedcentral.gov/picrender.fcgi?tool=pmcentrez&action=stream&blobt ype=pdf&artid=214999
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Molecular studies on the mechanism of tetracycline resistance mediated by Tet(O). by Manavathu EK, Fernandez CL, Cooperman BS, Taylor DE.; 1990 Jan; http://www.pubmedcentral.gov/picrender.fcgi?tool=pmcentrez&action=stream&blobt ype=pdf&artid=171522
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Mutations in the tetA(B) gene that cause a change in substrate specificity of the tetracycline efflux pump. by Guay GG, Tuckman M, Rothstein DM.; 1994 Apr; http://www.pubmedcentral.gov/picrender.fcgi?tool=pmcentrez&action=stream&blobt ype=pdf&artid=284555
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N,N-dimethylglycyl-amido derivative of minocycline and 6-demethyl-6desoxytetracycline, two new glycylcyclines highly effective against tetracyclineresistant gram-positive cocci. by Goldstein FW, Kitzis MD, Acar JF.; 1994 Sep; http://www.pubmedcentral.gov/picrender.fcgi?tool=pmcentrez&action=stream&blobt ype=pdf&artid=284718
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Novel aerobic tetracycline resistance gene that chemically modifies tetracycline. by Speer BS, Salyers AA.; 1989 Jan; http://www.pubmedcentral.gov/picrender.fcgi?tool=pmcentrez&action=stream&blobt ype=pdf&artid=209567
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Novel retroviral vector transferring a suicide gene and a selectable marker gene with enhanced gene expression by using a tetracycline-responsive expression system. by Hwang JJ, Scuric Z, Anderson WF.; 1996 Nov; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&rendertype=abstr act&artid=190890
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Nucleotide sequence analysis of tetracycline resistance gene tetO from Streptococcus mutans DL5. by LeBlanc DJ, Lee LN, Titmas BM, Smith CJ, Tenover FC.; 1988 Aug; http://www.pubmedcentral.gov/picrender.fcgi?tool=pmcentrez&action=stream&blobt ype=pdf&artid=211336
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Nucleotide sequence and phylogeny of the tet(L) tetracycline resistance determinant encoded by plasmid pSTE1 from Staphylococcus hyicus. by Schwarz S, Cardoso M, Wegener HC.; 1992 Mar; http://www.pubmedcentral.gov/picrender.fcgi?tool=pmcentrez&action=stream&blobt ype=pdf&artid=190560
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Nucleotide sequence of the repressor gene of the TN10 tetracycline resistance determinant. by Postle K, Nguyen TT, Bertrand KP.; 1984 Jun 25; http://www.pubmedcentral.gov/picrender.fcgi?tool=pmcentrez&action=stream&blobt ype=pdf&artid=318884
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Nucleotide sequence of the tetM tetracycline resistance determinant of the streptococcal conjugative shuttle transposon Tn1545. by Martin P, Trieu-Cuot P, Courvalin P.; 1986 Sep 11; http://www.pubmedcentral.gov/picrender.fcgi?tool=pmcentrez&action=stream&blobt ype=pdf&artid=311716
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Nucleotide sequence of the Tn10 encoded tetracycline resistance gene. by Hillen W, Schollmeier K.; 1983 Jan 25; http://www.pubmedcentral.gov/picrender.fcgi?tool=pmcentrez&action=stream&blobt ype=pdf&artid=325731
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Occurrence of tetracycline-resistant Neisseria gonorrhoeae outside the United States. by Hawkey PM, Heritage J.; 1988 Jun; http://www.pubmedcentral.gov/picrender.fcgi?tool=pmcentrez&action=stream&blobt ype=pdf&artid=172318
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Overproduction of transposon Tn10-encoded tetracycline resistance protein results in cell death and loss of membrane potential. by Eckert B, Beck CF.; 1989 Jun; http://www.pubmedcentral.gov/picrender.fcgi?tool=pmcentrez&action=stream&blobt ype=pdf&artid=210086
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Phenotypic and Molecular Characterization of Tetracycline- and ErythromycinResistant Strains of Streptococcus pneumoniae. by Montanari MP, Cochetti I, Mingoia M, Varaldo PE.; 2003 Jul; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=161878
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Plasmid-mediated tetracycline resistance in Campylobacter jejuni: expression in Escherichia coli and identification of homology with streptococcal class M determinant. by Taylor DE.; 1986 Mar; http://www.pubmedcentral.gov/picrender.fcgi?tool=pmcentrez&action=stream&blobt ype=pdf&artid=214536
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Plasmid-mediated tetracycline resistance in Haemophilus ducreyi. by Albritton WL, Maclean IW, Slaney LA, Ronald AR, Deneer HG.; 1984 Feb; http://www.pubmedcentral.gov/picrender.fcgi?tool=pmcentrez&action=stream&blobt ype=pdf&artid=185471
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Predisposing factors in Pneumocystis carinii pneumonia: effects of tetracycline, protein malnutrition, and corticosteroids on hosts. by Walzer PD, LaBine M, Redington TJ, Cushion MT.; 1984 Dec; http://www.pubmedcentral.gov/picrender.fcgi?tool=pmcentrez&action=stream&blobt ype=pdf&artid=261608
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Protection against endotoxic shock and lipopolysaccharide-induced local inflammation by tetracycline: correlation with inhibition of cytokine secretion. by Shapira L, Soskolne WA, Houri Y, Barak V, Halabi A, Stabholz A.; 1996 Mar; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&rendertype=abstr act&artid=173843
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Rapid Retroviral Delivery of Tetracycline-Inducible Genes in a Single Autoregulatory Cassette. by Hofmann A, Nolan GP, Blau HM.; 1996 May 28; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&rendertype=abstr act&artid=39219
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Regions in Bacteroides plasmids pBFTM10 and pB8-51 that allow Escherichia coliBacteroides shuttle vectors to be mobilized by IncP plasmids and by a conjugative Bacteroides tetracycline resistance element. by Shoemaker NB, Getty C, Guthrie EP, Salyers AA.; 1986 Jun; http://www.pubmedcentral.gov/picrender.fcgi?tool=pmcentrez&action=stream&blobt ype=pdf&artid=215218
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Relatedness of tetracycline resistance plasmids among species of coagulase-negative staphylococci. by Cooksey RC, Baldwin JN.; 1985 Feb; http://www.pubmedcentral.gov/picrender.fcgi?tool=pmcentrez&action=stream&blobt ype=pdf&artid=176245
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Resistance to tetracycline, erythromycin, and clindamycin in the Bacteroides fragilis group: inducible versus constitutive tetracycline resistance. by Privitera G, Fayolle F, Sebald M.; 1981 Sep; http://www.pubmedcentral.gov/picrender.fcgi?tool=pmcentrez&action=stream&blobt ype=pdf&artid=181693
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Reversal of Tetracycline Resistance Mediated by Different Bacterial Tetracycline Resistance Determinants by an Inhibitor of the Tet(B) Antiport Protein. by Nelson ML, Levy SB.; 1999 Jul; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=89350
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Role of efflux pump(s) in intrinsic resistance of Pseudomonas aeruginosa: resistance to tetracycline, chloramphenicol, and norfloxacin. by Li XZ, Livermore DM, Nikaido H.; 1994 Aug; http://www.pubmedcentral.gov/picrender.fcgi?tool=pmcentrez&action=stream&blobt ype=pdf&artid=284630
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Role of outer membrane barrier in efflux-mediated tetracycline resistance of Escherichia coli. by Thanassi DG, Suh GS, Nikaido H.; 1995 Feb; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&rendertype=abstr act&artid=176695
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Role of oxygen radicals in the phototoxicity of tetracyclines toward Escherichia coli B. by Martin JP Jr, Colina K, Logsdon N.; 1987 Jun; http://www.pubmedcentral.gov/picrender.fcgi?tool=pmcentrez&action=stream&blobt ype=pdf&artid=212109
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Role of tetracycline in pathogenesis of chronic candidiasis of rat tongues. by Allen CM, Beck FM, Lurie FA, Pinsky HM.; 1985 Feb; http://www.pubmedcentral.gov/picrender.fcgi?tool=pmcentrez&action=stream&blobt ype=pdf&artid=263195
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Screening of type Ia and Ib Streptococcus agalactiae strains with high sialic acid levels by determination of susceptibility to tetracyclines. by Nagano Y, Nagano N, Takahashi S, Suzuki A, Okuwaki Y.; 1989 Dec; http://www.pubmedcentral.gov/picrender.fcgi?tool=pmcentrez&action=stream&blobt ype=pdf&artid=267123
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Self-contained, tetracycline-regulated retroviral vector system for gene delivery to mammalian cells. by Paulus W, Baur I, Boyce FM, Breakefield XO, Reeves SA.; 1996 Jan; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&rendertype=abstr act&artid=189788
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Sensitive assay for measuring tetracycline levels in gingival crevice fluid. by Gordon JM, Walker CB, Goodson JM, Socransky SS.; 1980 Feb; http://www.pubmedcentral.gov/picrender.fcgi?tool=pmcentrez&action=stream&blobt ype=pdf&artid=283757
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Sensitive biological detection method for tetracyclines using a tetA-lacZ fusion system. by Chopra I, Hacker K, Misulovin Z, Rothstein DM.; 1990 Jan; http://www.pubmedcentral.gov/picrender.fcgi?tool=pmcentrez&action=stream&blobt ype=pdf&artid=171530
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Simian virus 40 promoters direct expression of the tetracycline gene in plasmid pACYC184. by Jenkins FJ, Howett MK, Rapp F.; 1983 Jan; http://www.pubmedcentral.gov/picrender.fcgi?tool=pmcentrez&action=stream&blobt ype=pdf&artid=256434
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Single-dose treatment of cholera with furazolidone or tetracycline in a double-blind randomized trial. by Rabbani GH, Islam MR, Butler T, Shahrier M, Alam K.; 1989 Sep; http://www.pubmedcentral.gov/picrender.fcgi?tool=pmcentrez&action=stream&blobt ype=pdf&artid=172681
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Standardization of disk diffusion and agar dilution susceptibility tests for Neisseria gonorrhoeae: interpretive criteria and quality control guidelines for ceftriaxone, penicillin, spectinomycin, and tetracycline. by Jones RN, Gavan TL, Thornsberry C, Fuchs PC, Gerlach EH, Knapp JS, Murray P, Washington JA 2nd.; 1989 Dec; http://www.pubmedcentral.gov/picrender.fcgi?tool=pmcentrez&action=stream&blobt ype=pdf&artid=267122
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Streptococcal tetracycline resistance mediated at the level of protein synthesis. by Burdett V.; 1986 Feb; http://www.pubmedcentral.gov/picrender.fcgi?tool=pmcentrez&action=stream&blobt ype=pdf&artid=214456
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Streptogramin- and tetracycline-responsive dual regulated expression of p27Kip1 sense and antisense enables positive and negative growth control of Chinese hamster ovary cells. by Fux C, Moser S, Schlatter S, Rimann M, Bailey JE, Fussenegger M.; 2001 Feb 15; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=29626
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Structural requirements of tetracycline-Tet repressor interaction: determination of equilibrium binding constants for tetracycline analogs with the Tet repressor. by Degenkolb J, Takahashi M, Ellestad GA, Hillen W.; 1991 Aug; http://www.pubmedcentral.gov/picrender.fcgi?tool=pmcentrez&action=stream&blobt ype=pdf&artid=245224
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Structure and function in rhodopsin: A tetracycline-inducible system in stable mammalian cell lines for high-level expression of opsin mutants. by Reeves PJ, Kim JM, Khorana HG.; 2002 Oct 15; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=129687
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Structure and function in rhodopsin: High-level expression of rhodopsin with restricted and homogeneous N-glycosylation by a tetracycline-inducible Nacetylglucosaminyltransferase I-negative HEK293S stable mammalian cell line. by Reeves PJ, Callewaert N, Contreras R, Khorana HG.; 2002 Oct 15; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=129688
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Subcellular Localization, Stability, and trans-Cleavage Competence of the Hepatitis C Virus NS3-NS4A Complex Expressed in Tetracycline-Regulated Cell Lines. by Wolk B, Sansonno D, Krausslich HG, Dammacco F, Rice CM, Blum HE, Moradpour D.; 2000 Mar 1; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=111711
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Subinhibitory concentrations of tetracycline alter fibrinogen binding by Bacteroides intermedius. by Lantz MS, Ray T, Krishnasami S, Pearson DE.; 1987 Dec; http://www.pubmedcentral.gov/picrender.fcgi?tool=pmcentrez&action=stream&blobt ype=pdf&artid=175827
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Suppression of polymorphonuclear leukocyte chemotactic factor production in Propionibacterium acnes by subminimal inhibitory concentrations of tetracycline, ampicillin, minocycline, and erythromycin. by Webster GF, Leyden JJ, McGinley KJ, McArthur WP.; 1982 May; http://www.pubmedcentral.gov/picrender.fcgi?tool=pmcentrez&action=stream&blobt ype=pdf&artid=182009
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Susceptibilities of Campylobacter jejuni Isolates from Germany to Ciprofloxacin, Moxifloxacin, Erythromycin, Clindamycin, and Tetracycline. by Wagner J, Jabbusch M, Eisenblatter M, Hahn H, Wendt C, Ignatius R.; 2003 Jul; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=161846
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Susceptibilities of Eikenella corrodens, Prevotella intermedia, and Prevotella nigrescens Clinical Isolates to Amoxicillin and Tetracycline. by Luong N, Tsai J, Chen C.; 2001 Nov; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=90820
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Susceptibilities of Mycoplasma hominis, M. pneumoniae, and Ureaplasma urealyticum to GAR-936, Dalfopristin, Dirithromycin, Evernimicin, Gatifloxacin, Linezolid, Moxifloxacin, Quinupristin-Dalfopristin, and Telithromycin Compared to Their Susceptibilities to Reference Macrolides, Tetracyclines, and Quinolones. by Kenny GE, Cartwright FD.; 2001 Sep; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=90699
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Susceptibilities of Mycoplasma hominis, Mycoplasma pneumoniae, and Ureaplasma urealyticum to new glycylcyclines in comparison with those to older tetracyclines. by Kenny GE, Cartwright FD.; 1994 Nov; http://www.pubmedcentral.gov/picrender.fcgi?tool=pmcentrez&action=stream&blobt ype=pdf&artid=188253
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Susceptibility In Vitro and In Vivo of Pseudomonas pseudomallei to Rifampin and Tetracyclines. by Fisher MW, Hillegas AB, Nazeeri PL.; 1971 Jul; http://www.pubmedcentral.gov/picrender.fcgi?tool=pmcentrez&action=stream&blobt ype=pdf&artid=377368
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Susceptibility of Mycoplasma pneumoniae to several new quinolones, tetracycline, and erythromycin. by Kenny GE, Cartwright FD.; 1991 Mar; http://www.pubmedcentral.gov/picrender.fcgi?tool=pmcentrez&action=stream&blobt ype=pdf&artid=245057
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Susceptibility testing of Dientamoeba fragilis ATCC 30948 with iodoquinol, paromomycin, tetracycline, and metronidazole. by Chan FT, Guan MX, Mackenzie AM, Diaz-Mitoma F.; 1994 May; http://www.pubmedcentral.gov/picrender.fcgi?tool=pmcentrez&action=stream&blobt ype=pdf&artid=188168
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Susceptible Escherichia coli cells can actively excrete tetracyclines. by McMurry LM, Aronson DA, Levy SB.; 1983 Oct; http://www.pubmedcentral.gov/picrender.fcgi?tool=pmcentrez&action=stream&blobt ype=pdf&artid=185371
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Temporal Control of Gene Expression in Transgenic Mice by a TetracyclineResponsive Promoter. by Furth PA, Onge LS, Boger H, Gruss P, Gossen M, Kistner A, Bujard H, Hennighausen L.; 1994 Sep 27; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&rendertype=abstr act&artid=44800
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Tet B or not tet B: Advances in tetracycline-inducible gene expression. by Blau HM, Rossi FM.; 1999 Feb 2; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=33520
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Tet determinants provide poor protection against some tetracyclines: further evidence for division of tetracyclines into two classes. by Oliva B, Chopra I.; 1992 Apr; http://www.pubmedcentral.gov/picrender.fcgi?tool=pmcentrez&action=stream&blobt ype=pdf&artid=189478
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Tet protein domains interact productively to mediate tetracycline resistance when present on separate polypeptides. by Rubin RA, Levy SB.; 1991 Jul; http://www.pubmedcentral.gov/picrender.fcgi?tool=pmcentrez&action=stream&blobt ype=pdf&artid=208114
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Tet(M)-promoted release of tetracycline from ribosomes is GTP dependent. by Burdett V.; 1996 Jun; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&rendertype=abstr act&artid=178077
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tetA(L) Mutants of a Tetracycline-Sensitive Strain of Bacillus subtilis with the Polynucleotide Phosphorylase Gene Deleted. by Bechhofer DH, Stasinopoulos SJ.; 1998 Jul 1; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=107306
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Tetracycline Antibiotics: Mode of Action, Applications, Molecular Biology, and Epidemiology of Bacterial Resistance. by Chopra I, Roberts M.; 2001 Jun; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=99026
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Tetracycline diffusion through phospholipid bilayers and binding to phospholipids. by Argast M, Beck CF.; 1984 Aug; http://www.pubmedcentral.gov/picrender.fcgi?tool=pmcentrez&action=stream&blobt ype=pdf&artid=284133
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Tetracycline Induces Stabilization of mRNA in Bacillus subtilis. by Wei Y, Bechhofer DH.; 2002 Feb; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=134818
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Tetracycline Inhibition of a Lipase from Corynebacterium acnes. by Weaber K, Freedman R, Eudy WW.; 1971 Apr; http://www.pubmedcentral.gov/picrender.fcgi?tool=pmcentrez&action=stream&blobt ype=pdf&artid=377246
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Tetracycline Rapidly Reaches All the Constituent Cells of Uropathogenic Escherichia coli Biofilms. by Stone G, Wood P, Dixon L, Keyhan M, Matin A.; 2002 Aug; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=127323
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Tetracycline repressor-regulated gene repression in recombinant human cytomegalovirus. by Kim HJ, Gatz C, Hillen W, Jones TR.; 1995 Apr; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&rendertype=abstr act&artid=188934
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Tetracycline resistance and TetM in oral anaerobic bacteria and Neisseria perflava-N. sicca. by Roberts MC, Moncla BJ.; 1988 Aug; http://www.pubmedcentral.gov/picrender.fcgi?tool=pmcentrez&action=stream&blobt ype=pdf&artid=172392
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Tetracycline resistance and tetM in pathogenic urogenital bacteria. by Roberts MC, Hillier SL, Hale J, Holmes KK, Kenny GE.; 1986 Nov; http://www.pubmedcentral.gov/picrender.fcgi?tool=pmcentrez&action=stream&blobt ype=pdf&artid=176543
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Tetracycline resistance element of pBR322 mediates potassium transport. by Dosch DC, Salvacion FF, Epstein W.; 1984 Dec; http://www.pubmedcentral.gov/picrender.fcgi?tool=pmcentrez&action=stream&blobt ype=pdf&artid=215843
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Tetracycline resistance genes from Bacillus plasmid pAB124 confer decreased accumulation of the antibiotic in Bacillus subtilis but not in Escherichia coli. by Eccles S, Docherty A, Chopra I, Shales S, Ball P.; 1981 Mar; http://www.pubmedcentral.gov/picrender.fcgi?tool=pmcentrez&action=stream&blobt ype=pdf&artid=217148
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Tetracycline resistance transposon Tn1721: recA-dependent gene amplification and expression of tetracycline resistance. by Wiebauer K, Schraml S, Shales SW, Schmitt R.; 1981 Sep; http://www.pubmedcentral.gov/picrender.fcgi?tool=pmcentrez&action=stream&blobt ype=pdf&artid=216121
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Tetracycline/H+ antiport and Na+/H+ antiport catalyzed by the Bacillus subtilis TetA(L) transporter expressed in Escherichia coli. by Guffanti AA, Krulwich TA.; 1995 Aug; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&rendertype=abstr act&artid=177215
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Tetracycline-controlled transcription in eukaryotes: novel transactivators with graded transactivation potential. by Baron U, Gossen M, Bujard H.; 1997 Jul 15; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&rendertype=abstr act&artid=146828
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Tetracycline-dependent appearance of plasmidlike forms in Bacteroides uniformis 0061 mediated by conjugal Bacteroides tetracycline resistance elements. by Shoemaker NB, Salyers AA.; 1988 Apr; http://www.pubmedcentral.gov/picrender.fcgi?tool=pmcentrez&action=stream&blobt ype=pdf&artid=211013
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Tetracycline-inducible expression systems with reduced basal activity in mammalian cells. by Forster K, Helbl V, Lederer T, Urlinger S, Wittenburg N, Hillen W.; 1999 Jan 15; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&rendertype=abstr act&artid=148237
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Tetracycline-inducible systems for Drosophila. by Stebbins MJ, Urlinger S, Byrne G, Bello B, Hillen W, Yin JC.; 2001 Sep 11; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=58551
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Tetracycline-inducible transfer of tetracycline resistance in Bacteroides fragilis in the absence of detectable plasmid DNA. by Rashtchian A, Dubes GR, Booth SJ.; 1982 Apr; http://www.pubmedcentral.gov/picrender.fcgi?tool=pmcentrez&action=stream&blobt ype=pdf&artid=220092
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Tetracycline-Regulatable System To Tightly Control Gene Expression in the Pathogenic Fungus Candida albicans. by Nakayama H, Mio T, Nagahashi S, Kokado M, Arisawa M, Aoki Y.; 2000 Dec; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=97771
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Tetracycline-Regulated Suppression of Amber Codons in Mammalian Cells. by Park HJ, RajBhandary UL.; 1998 Aug; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=109027
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Tetracycline-resistant L-forms isolated from an antibiotic-susceptible strain of Listeria monocytogenes. by Schmitt-Slomska J, Marmouset MC, Louis C, Bally R, Starka G, Madoff S.; 1982 Oct; http://www.pubmedcentral.gov/picrender.fcgi?tool=pmcentrez&action=stream&blobt ype=pdf&artid=183813
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Tetracycline-resistant Mycoplasma hominis strains contain streptococcal tetM sequences. by Roberts MC, Koutsky LA, Holmes KK, LeBlanc DJ, Kenny GE.; 1985 Jul; http://www.pubmedcentral.gov/picrender.fcgi?tool=pmcentrez&action=stream&blobt ype=pdf&artid=176326
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Tetracycline-reversible silencing of eukaryotic promoters. by Deuschle U, Meyer WK, Thiesen HJ.; 1995 Apr; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&rendertype=abstr act&artid=230416
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Tetracyclines affect prion infectivity. by Forloni G, Iussich S, Awan T, Colombo L, Angeretti N, Girola L, Bertani I, Poli G, Caramelli M, Grazia Bruzzone M, Farina L, Limido L, Rossi G, Giaccone G, Ironside JW, Bugiani O, Salmona M, Tagliavini F.; 2002 Aug 6; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=125061
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Tetracyclines inhibit microglial activation and are neuroprotective in global brain ischemia. by Yrjanheikki J, Keinanen R, Pellikka M, Hokfelt T, Koistinaho J.; 1998 Dec 22; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=28119
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The cryptic tetracycline resistance determinant on Tn4400 mediates tetracycline degradation as well as tetracycline efflux. by Park BH, Levy SB.; 1988 Dec; http://www.pubmedcentral.gov/picrender.fcgi?tool=pmcentrez&action=stream&blobt ype=pdf&artid=176021
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The region of a Bacteroides conjugal chromosomal tetracycline resistance element which is responsible for production of plasmidlike forms from unlinked chromosomal DNA might also be involved in transfer of the element. by Stevens AM, Shoemaker NB, Salyers AA.; 1990 Aug; http://www.pubmedcentral.gov/picrender.fcgi?tool=pmcentrez&action=stream&blobt ype=pdf&artid=213251
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The TetA(K) Tetracycline/H + Antiporter from Staphylococcus aureus: Mutagenesis and Functional Analysis of Motif C. by Ginn SL, Brown MH, Skurray RA.; 2000 Mar 15; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=94444
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The tetracycline-responsive promoter contains functional interferon-inducible response elements. by Rang A, Will H.; 2000 Mar 1; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=102598
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Tight Control of Gene Expression in Mammalian Cells by Tetracycline-Responsive Promoters. by Gossen M, Bujard H.; 1992 Jun 15; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&rendertype=abstr act&artid=49329
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Tn1721-encoded tetracycline resistance: mapping of structural and regulatory genes mediating resistance. by Altenbuchner J, Schmid K, Schmitt R.; 1983 Jan; http://www.pubmedcentral.gov/picrender.fcgi?tool=pmcentrez&action=stream&blobt ype=pdf&artid=217348
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Transfer of the conjugal tetracycline resistance transposon Tn916 from Streptococcus faecalis to Staphylococcus aureus and identification of some insertion sites in the staphylococcal chromosome. by Jones JM, Yost SC, Pattee PA.; 1987 May; http://www.pubmedcentral.gov/picrender.fcgi?tool=pmcentrez&action=stream&blobt ype=pdf&artid=212108
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Transport of the lipophilic analog minocycline differs from that of tetracycline in susceptible and resistant Escherichia coli strains. by McMurry LM, Cullinane JC, Levy SB.; 1982 Nov; http://www.pubmedcentral.gov/picrender.fcgi?tool=pmcentrez&action=stream&blobt ype=pdf&artid=185662
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Transposon Tn10-like tetracycline resistance determinants in Haemophilus parainfluenzae. by Levy SB, Buu-Hoi A, Marshall B.; 1984 Oct; http://www.pubmedcentral.gov/picrender.fcgi?tool=pmcentrez&action=stream&blobt ype=pdf&artid=214685
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tRNA modification activity is necessary for Tet(M)-mediated tetracycline resistance. by Burdett V.; 1993 Nov; http://www.pubmedcentral.gov/picrender.fcgi?tool=pmcentrez&action=stream&blobt ype=pdf&artid=206862
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Twelve-Transmembrane-Segment (TMS) Version ([Delta]TMS VII-VIII) of the 14TMS Tet(L) Antibiotic Resistance Protein Retains Monovalent Cation Transport Modes but Lacks Tetracycline Efflux Capacity. by Jin J, Guffanti AA, Beck C, Krulwich TA.; 2001 Apr 15; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=95185
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Two complementation groups mediate tetracycline resistance determined by Tn10. by Curiale MS, Levy SB.; 1982 Jul; http://www.pubmedcentral.gov/picrender.fcgi?tool=pmcentrez&action=stream&blobt ype=pdf&artid=220228
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Two Transport Systems for Tetracycline in Sensitive Escherichia coli: Critical Role for an Initial Rapid Uptake System Insensitive to Energy Inhibitors. by McMurry L, Levy SB.; 1978 Aug; http://www.pubmedcentral.gov/picrender.fcgi?tool=pmcentrez&action=stream&blobt ype=pdf&artid=352433
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Uptake of 3H-Tetracycline by Resistant and Sensitive Escherichia coli. by Reynard AM, Nellis LF, Beck ME.; 1971 Jan; http://www.pubmedcentral.gov/picrender.fcgi?tool=pmcentrez&action=stream&blobt ype=pdf&artid=377119
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Use of high-performance liquid chromatography to monitor stability of tetracycline and chlortetracycline in susceptibility determinations. by Ray A, Newton V.; 1991 Jun; http://www.pubmedcentral.gov/picrender.fcgi?tool=pmcentrez&action=stream&blobt ype=pdf&artid=284329
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Use of the human EF-1alpha promoter for expression can significantly increase success in establishing stable cell lines with consistent expression: a study using the tetracycline-inducible system in human cancer cells. by Gopalkrishnan RV, Christiansen KA, Goldstein NI, DePinho RA, Fisher PB.; 1999 Dec 15; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&rendertype=abstr act&artid=148778
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Widespread Distribution of a Tet W Determinant among Tetracycline-Resistant Isolates of the Animal Pathogen Arcanobacterium pyogenes. by Billington SJ, Songer JG, Jost BH.; 2002 May; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=127165
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.
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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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To generate your own bibliography of studies dealing with tetracycline, simply go to the PubMed Web site at http://www.ncbi.nlm.nih.gov/pubmed. Type “tetracycline” (or synonyms) into the search box, and click “Go.” The following is the type of output you can expect from PubMed for tetracycline (hyperlinks lead to article summaries): •
A case of co-incident phenylketonuria, pemphigus foliaceus, and tinea amiantacea treated with tetracycline and nicotinamide. Author(s): Scheinfeld N. Source: J Drugs Dermatol. 2003 April; 2(2): 202-5. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12852375
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A complex adenovirus vector that delivers FASL-GFP with combined prostatespecific and tetracycline-regulated expression. Author(s): Rubinchik S, Wang D, Yu H, Fan F, Luo M, Norris JS, Dong JY. Source: Molecular Therapy : the Journal of the American Society of Gene Therapy. 2001 November; 4(5): 416-26. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11708878
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A double-blind study on the effectiveness of tetracycline in reducing the incidence of fibrinolytic alveolitis. Author(s): Swanson AE. Source: Journal of Oral and Maxillofacial Surgery : Official Journal of the American Association of Oral and Maxillofacial Surgeons. 1989 February; 47(2): 165-7. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=2913252
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A new approach to treatment of tetracycline stained teeth: report of a case. Author(s): Mouradian WF, Graham D, Fernald L. Source: Asdc J Dent Child. 1976 March-April; 43(2): 103-5. No Abstract Available. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=767377
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A new tetracycline minocycline compared with ampicillin in general practice. Author(s): Gallagher DJ, Settle KL. Source: N Z Med J. 1976 February 25; 83(558): 105-7. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=1063924
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A novel single tetracycline-regulative adenoviral vector for tumor-specific Bax gene expression and cell killing in vitro and in vivo. Author(s): Gu J, Zhang L, Huang X, Lin T, Yin M, Xu K, Ji L, Roth JA, Fang B. Source: Oncogene. 2002 July 18; 21(31): 4757-64. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12101414
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A novel tetracycline-controlled transactivator-transrepressor system enables external control of oncolytic adenovirus replication. Author(s): Fechner H, Wang X, Srour M, Siemetzki U, Seltmann H, Sutter AP, Scherubl H, Zouboulis CC, Schwaab R, Hillen W, Schultheiss HP, Poller W. Source: Gene Therapy. 2003 September; 10(19): 1680-90. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12923567
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A tetracycline-based histomorphometric evaluation of bone resorption and bone turnover in hyperthyroidism and hyperparathyroidism. Author(s): Mosekilde L, Melsen F. Source: Acta Med Scand. 1978; 204(1-2): 97-102. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=685737
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A tetracycline-regulated adenoviral expression system for in vivo delivery of transgenes to lung and liver. Author(s): Tietge UJ, Kozarsky KF, Donahee MH, Rader DJ. Source: The Journal of Gene Medicine. 2003 July; 5(7): 567-75. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12825196
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A versatile new mineralized bone stain for simultaneous assessment of tetracycline and osteoid seams. Author(s): Villanueva AR, Lundin KD. Source: Stain Technol. 1989 May; 64(3): 129-38. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=2480003
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Allergy to a tetracycline preparation-a case report. Author(s): Fawcett IW, Pepys J. Source: Clin Allergy. 1976 May; 6(3): 301-4. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=939039
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Amoxicillin/tetracycline combinations are inadequate as alternative therapies for Helicobacter pylori infection. Author(s): Perri F, Festa V, Merla A, Quitadamo M, Clemente R, Andriulli A. Source: Helicobacter. 2002 April; 7(2): 99-104. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11966868
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An adenoviral system for tetracycline-regulated TGF-beta expression mediates a reversible cell cycle arrest. Author(s): Wettergreen MA, Hunniford JW, Crawford JM, Adami GR. Source: European Journal of Oral Sciences. 2001 December; 109(6): 415-21. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11767279
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An ecdysone and tetracycline dual regulatory expression system for studies on Rac1 small GTPase-mediated signaling. Author(s): Lai JF, Juang SH, Hung YM, Cheng HY, Cheng TL, Mostov KE, Jou TS. Source: American Journal of Physiology. Cell Physiology. 2003 September; 285(3): C7119. Epub 2003 May 07. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12736135
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Antibiotic resistance and distribution of tetracycline resistance genes in Escherichia coli O157:H7 isolates from humans and bovines. Author(s): Wilkerson C, Samadpour M, van Kirk N, Roberts MC. Source: Antimicrobial Agents and Chemotherapy. 2004 March; 48(3): 1066-7. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=14982813
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Antiepiligrin cicatricial pemphigoid of the larynx successfully treated with a combination of tetracycline and niacinamide. Author(s): Sakamoto K, Mori K, Hashimoto T, Yancey KB, Nakashima T. Source: Archives of Otolaryngology--Head & Neck Surgery. 2002 December; 128(12): 1420-3. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12479732
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Anti-inflammatory effects of erythromycin and tetracycline on Propionibacterium acnes induced production of chemotactic factors and reactive oxygen species by human neutrophils. Author(s): Jain A, Sangal L, Basal E, Kaushal GP, Agarwal SK. Source: Dermatology Online Journal [electronic Resource]. 2002 October; 8(2): 2. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12546757
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Application of a local drug delivery system to periodontal therapy: I. Development of collagen preparations with immobilized tetracycline. Author(s): Minabe M, Uematsu A, Nishijima K, Tomomatsu E, Tamura T, Hori T, Umemoto T, Hino T. Source: J Periodontol. 1989 February; 60(2): 113-7. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=2656975
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Assessing the role of multiple phosphoinositide 3-kinases in chemokine signaling: use of dominant negative mutants controlled by a tetracycline-regulated gene expression system. Author(s): Curnock AP, Sotsios Y, Ward SG. Source: Methods in Molecular Biology (Clifton, N.J.). 2004; 239: 211-22. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=14573921
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Azelaic acid for the treatment of acne. A clinical comparison with oral tetracycline. Author(s): Hjorth N, Graupe K. Source: Acta Derm Venereol Suppl (Stockh). 1989; 143: 45-8. No Abstract Available. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=2528259
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Bacterial resistance to tetracycline: mechanisms, transfer, and clinical significance. Author(s): Speer BS, Shoemaker NB, Salyers AA. Source: Clinical Microbiology Reviews. 1992 October; 5(4): 387-99. Review. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=1423217
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Bacteriological and clinical assessment of tetracycline as root conditioning in adjunct to periodontal surgery. Author(s): Darhous MS, Zahran F, Ragy N. Source: Egypt Dent J. 1995 April; 41(2): 1167-78. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=9497653
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Balanitis as a fixed drug eruption to tetracycline. Author(s): Dodds PR, Chi TN. Source: The Journal of Urology. 1985 June; 133(6): 1044-5. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=3158749
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Beneficial effect of systemic tetracycline therapy in the treatment of noninfected corneal ulcers. Author(s): Perry HD, Golub LM. Source: Cornea. 1984; 3(1): 75. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=6536426
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Bi-directional gene switching with the tetracycline repressor and a novel tetracycline antagonist. Author(s): Chrast-Balz J, Hooft van Huijsduijnen R. Source: Nucleic Acids Research. 1996 August 1; 24(15): 2900-4. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=8760871
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Bilateral spontaneous pneumothorax in AIDS--successful treatment with talc pleurodesis following failure with tetracycline sclerotherapy. Author(s): Nageswaran A, Priestley CJ, Patel R, Kyi TT, Kinghorn GR. Source: International Journal of Std & Aids. 1994 July-August; 5(4): 296-8. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=7948164
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Bioavailability of different brands of tetracycline in undernourished subjects. Author(s): Santosh KK, Raghuram TC, Krishnaswamy K. Source: Int J Clin Pharmacol Ther Toxicol. 1992 January; 30(1): 13-7. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=1551739
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Biodegradable microparticles for sustained delivery of tetracycline to the periodontal pocket: formulatory and drug release studies. Author(s): Esposito E, Cortesi R, Cervellati F, Menegatti E, Nastruzzi C. Source: Journal of Microencapsulation. 1997 March-April; 14(2): 175-87. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=9132469
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Bioerodible injectable poly(ortho ester) for tetracycline controlled delivery to periodontal pockets: preliminary trial in humans. Author(s): Schwach-Abdellaoui K, Loup PJ, Vivien-Castioni N, Mombelli A, Baehni P, Barr J, Heller J, Gurny R. Source: Aaps Pharmsci [electronic Resource]. 2002; 4(4): E20. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12645992
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Bismuth-based quadruple therapy using a single capsule of bismuth biskalcitrate, metronidazole, and tetracycline given with omeprazole versus omeprazole, amoxicillin, and clarithromycin for eradication of Helicobacter pylori in duodenal ulcer patients: a prospective, randomized, multicenter, North American trial. Author(s): Laine L, Hunt R, El-Zimaity H, Nguyen B, Osato M, Spenard J. Source: The American Journal of Gastroenterology. 2003 March; 98(3): 562-7. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12650788
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Bismuth-based quadruple therapy with bismuth subcitrate, metronidazole, tetracycline and omeprazole in the eradication of Helicobacter pylori. Author(s): Lahaie R, Farley A, Dallaire C, Archambault A, Fallone CA, Ponich T, Hunt R, Oravec M, Whitsitt P, Van Zanten SV, Marcon N, Bailey R, Dumont A, Nguyen B, Desrochers S, Spenard J. Source: Canadian Journal of Gastroenterology = Journal Canadien De Gastroenterologie. 2001 September; 15(9): 581-5. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11573100
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Bismuth-based triple therapy with bismuth subcitrate, metronidazole and tetracycline in the eradication of Helicobacter pylori: a randomized, placebo controlled, doubleblind study. Author(s): Veldhuyzen Van Zanten S, Farley A, Marcon N, Lahaie R, Archambault A, Hunt R, Bailey R, Owen D, Spenard J, Stiglick A, Aimola N, Colin P. Source: Canadian Journal of Gastroenterology = Journal Canadien De Gastroenterologie. 2000 July-August; 14(7): 599-602. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=10978947
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Bleaching teeth discolored by tetracycline therapy. Author(s): Hayashi K, Takamizu M, Momoi Y, Furuya K, Kusunoki M, Kono A. Source: Dent Surv. 1980 March; 56(3): 17-25. No Abstract Available. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=6933119
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Bleaching tetracycline stains. Author(s): Zillich RM. Source: Compend Contin Educ Dent. 1984 June; 5(6): 465-7. No Abstract Available. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=6594213
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Bleaching tetracycline-stained teeth. A combined approach. Author(s): Weinberg SP. Source: Dent Today. 1997 August; 16(8): 56, 58-9. No Abstract Available. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=9558499
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Bleomycin and tetracycline in malignant pleural effusions: a review. Author(s): Moffett MJ, Ruckdeschel JC. Source: Seminars in Oncology. 1992 April; 19(2 Suppl 5): 59-62; Discussion 62-3. Review. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=1384146
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Bonded porcelain veneer masking of dark tetracycline dentinal stains. Author(s): Cavanaugh RR, Croll TP. Source: Pract Periodontics Aesthet Dent. 1994 January-February; 6(1): 71-9; Quiz 80. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=8180372
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Bone formation periods studied with triple tetracycline labels in women with postmenopausal osteoporosis. Author(s): Ott SM. Source: Journal of Bone and Mineral Research : the Official Journal of the American Society for Bone and Mineral Research. 1993 April; 8(4): 443-50. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=8475794
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Bullous pemphigoid controlled by tetracycline. Author(s): Thornfeldt CR, Menkes AW. Source: Journal of the American Academy of Dermatology. 1987 February; 16(2 Pt 1): 305-10. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=3546415
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Bullous pemphigoid successfully controlled by tetracycline and nicotinamide. Author(s): Kolbach DN, Remme JJ, Bos WH, Jonkman MF, De Jong MC, Pas HH, van der Meer JB. Source: The British Journal of Dermatology. 1995 July; 133(1): 88-90. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=7669647
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Characteristics of adenovirus-mediated tetracycline-controllable expression system. Author(s): Mizuguchi H, Hayakawa T. Source: Biochimica Et Biophysica Acta. 2001 November 7; 1568(1): 21-9. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11731081
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Chemiluminescent method for determination of tetracycline, chlortetracycline, minocycline, doxycycline, and demeclocycline. Author(s): Marczynski S. Source: Biopolymers. 2000; 57(6): 365-72. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11054656
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Clinical effects of local application of collagen film-immobilized tetracycline. Author(s): Minabe M, Takeuchi K, Tomomatsu E, Hori T, Umemoto T. Source: Journal of Clinical Periodontology. 1989 May; 16(5): 291-4. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=2723101
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CMT-3, a non-antimicrobial tetracycline (TC), inhibits MT1-MMP activity: relevance to cancer. Author(s): Lee HM, Golub LM, Cao J, Teronen O, Laitinen M, Salo T, Zucker S, Sorsa T. Source: Current Medicinal Chemistry. 2001 February; 8(3): 257-60. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11172680
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Combination therapy of tetracycline and tacrolimus resulting in rapid resolution of steroid-induced periocular rosacea. Author(s): Pabby A, An KP, Laws RA. Source: Cutis; Cutaneous Medicine for the Practitioner. 2003 August; 72(2): 141-2. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12953939
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Combined professional and home care nightguard bleaching of tetracycline-stained teeth. Author(s): Fiedler RS, Reichl RB. Source: Gen Dent. 2000 May-June; 48(3): 257-61. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11199590
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Combining treatment modalities for tetracycline-discolored teeth. Author(s): Sadan A, Lemon RR. Source: Int J Periodontics Restorative Dent. 1998 December; 18(6): 564-71. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=10321171
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Comparative effectiveness of tetracycline, minocycline and doxycycline in treatment of acute-on-chronic bronchitis. A study based on sputum levels. Author(s): Ruhen RW, Tandon MK. Source: The Medical Journal of Australia. 1976 February 7; 1(6): 151-3. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=1083475
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Comparative SEM study on the effect of root conditioning with EDTA or tetracycline Hcl on periodontally involved root surfaces. Author(s): Babay N. Source: Indian J Dent Res. 2000 April-June; 11(2): 53-7. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11307429
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Comparative trial of erythromycin and sulphatrimethoprim in the treatment of tetracycline-resistant Vibrio cholerae O1. Author(s): Burans JP, Podgore J, Mansour MM, Farah AH, Abbas S, Abu-Elyazeed R, Woody JN. Source: Transactions of the Royal Society of Tropical Medicine and Hygiene. 1989 November-December; 83(6): 836-8. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=2617655
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Comparison of the in vitro activity of the glycylcycline tigecycline (formerly GAR936) with those of tetracycline, minocycline, and doxycycline against isolates of nontuberculous mycobacteria. Author(s): Wallace RJ Jr, Brown-Elliott BA, Crist CJ, Mann L, Wilson RW. Source: Antimicrobial Agents and Chemotherapy. 2002 October; 46(10): 3164-7. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12234839
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Composition and antibiotic resistance profile of microcosm dental plaques before and after exposure to tetracycline. Author(s): Ready D, Roberts AP, Pratten J, Spratt DA, Wilson M, Mullany P. Source: The Journal of Antimicrobial Chemotherapy. 2002 May; 49(5): 769-75. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12003970
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Concentrations of tetracycline in human gingival tissue in patients with chronic periodontal disease. Author(s): Shifer A, Dany S, Schwarzkopf R, Rubinstein E. Source: The Journal of Antimicrobial Chemotherapy. 1989 March; 23(3): 464-5. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=2732129
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Conditional cell ablation by stringent tetracycline-dependent regulation of barnase in mammalian cells. Author(s): Leuchtenberger S, Perz A, Gatz C, Bartsch JW. Source: Nucleic Acids Research. 2001 August 15; 29(16): E76. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11504884
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Control of parvovirus DNA replication by a tetracycline-regulated repressor. Author(s): Maxwell IH, Maxwell F. Source: Gene Therapy. 1999 March; 6(3): 309-13. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=10435080
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Control of the functional activity of an antisense RNA by a tetracycline-responsive derivative of the human U6 snRNA promoter. Author(s): Ohkawa J, Taira K. Source: Human Gene Therapy. 2000 March 1; 11(4): 577-85. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=10724036
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Controlled local delivery of tetracycline with polymer strips in the treatment of periodontitis. Author(s): Friesen LR, Williams KB, Krause LS, Killoy WJ. Source: J Periodontol. 2002 January; 73(1): 13-9. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11846194
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Controlling gene expression in mice with tetracycline: application in pigment cell research. Author(s): Shin MK. Source: Pigment Cell Research / Sponsored by the European Society for Pigment Cell Research and the International Pigment Cell Society. 2000 October; 13(5): 326-31. Review. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11041208
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Correlation of in vitro resistance of Staphylococcus aureus to tetracycline, doxycycline, and minocycline with in vivo use. Author(s): Lewis SA, Altemeier WA. Source: Chemotherapy. 1976; 22(5): 319-23. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=947710
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Cytotoxic activity and inhibition of tumor cell invasion by derivatives of a chemically modified tetracycline CMT-3 (COL-3). Author(s): Lokeshwar BL, Escatel E, Zhu B. Source: Current Medicinal Chemistry. 2001 February; 8(3): 271-9. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11172682
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Daily use of whitening strips on tetracycline-stained teeth: comparative results after 2 months. Author(s): Kugel G, Aboushala A, Zhou X, Gerlach RW. Source: Compend Contin Educ Dent. 2002 January; 23(1A): 29-34; Quiz 50. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11913291
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Debridement and local application of tetracycline-loaded fibres in the management of persistent periodontitis: results after 12 months. Author(s): Aimetti M, Romano F, Torta I, Cirillo D, Caposio P, Romagnoli R. Source: Journal of Clinical Periodontology. 2004 March; 31(3): 166-72. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=15016019
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Decrease in the incidence of tetracycline resistance in strains of Neisseria gonorrhoeae in the nineties. Author(s): Bodonaik NC. Source: The West Indian Medical Journal. 2003 September; 52(3): 228-30. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=14649105
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Dermatitis herpetiformis effectively treated with heparin, tetracycline and nicotinamide. Author(s): Shah SA, Ormerod AD. Source: Clinical and Experimental Dermatology. 2000 May; 25(3): 204-5. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=10844495
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Design, characterisation and preliminary clinical evaluation of a novel mucoadhesive topical formulation containing tetracycline for the treatment of periodontal disease. Author(s): Jones DS, Woolfson AD, Brown AF, Coulter WA, McClelland C, Irwin CR. Source: Journal of Controlled Release : Official Journal of the Controlled Release Society. 2000 July 3; 67(2-3): 357-68. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=10825567
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Detection of a novel Tet M determinant in tetracycline-resistant Neisseria gonorrhoeae from Uruguay, 1996-1999. Author(s): Marquez CM, Dillon JA, Rodriguez V, Borthagaray G. Source: Sexually Transmitted Diseases. 2002 December; 29(12): 792-7. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12466722
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Detection of high-level tetracycline resistance in clinical isolates of Helicobacter pylori using PCR-RFLP. Author(s): Ribeiro ML, Gerrits MM, Benvengo YH, Berning M, Godoy AP, Kuipers EJ, Mendonca S, van Vliet AH, Pedrazzoli J Jr, Kusters JG. Source: Fems Immunology and Medical Microbiology. 2004 January 15; 40(1): 57-61. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=14734187
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Detection of tet(M), tet(O) and tet(S) in tetracycline/minocycline-resistant Streptococcus pyogenes bacteraemia isolates. Author(s): Hammerum AM, Nielsen HU, Agerso Y, Ekelund K, Frimodt-Moller N. Source: The Journal of Antimicrobial Chemotherapy. 2004 January; 53(1): 118-9. Epub 2003 December 04. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=14657081
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Development and characterisation of tetracycline-regulated phosphoinositide 3kinase mutants: assessing the role of multiple phosphoinositide 3-kinases in chemokine signaling. Author(s): Curnock AP, Ward SG. Source: Journal of Immunological Methods. 2003 February; 273(1-2): 29-41. Review. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12535795
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Development of a self-assembling nuclear targeting vector system based on the tetracycline repressor protein. Author(s): Vaysse L, Harbottle R, Bigger B, Bergau A, Tolmachov O, Coutelle C. Source: The Journal of Biological Chemistry. 2004 February 13; 279(7): 5555-64. Epub 2003 November 07. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=14607832
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Differential expression of the tetracycline-controlled transactivator-driven human CYP1B1 gene in double-transgenic mice is due to androgens: application for detecting androgens and antiandrogens. Author(s): Hwang DY, Cho JS, Chae KR, Kang TS, Hwang JH, Lim CH, Lee SH, Lim HJ, Min SH, Sheen YY, Jang IS, Kim YK. Source: Archives of Biochemistry and Biophysics. 2003 July 15; 415(2): 137-45. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12831835
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Discolouration of permanent teeth and enamel hypoplasia due to tetracycline. Author(s): Kashyap AS, Sharma HS. Source: Postgraduate Medical Journal. 1999 December; 75(890): 772. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=10755912
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Distribution and in-vitro transfer of tetracycline resistance determinants in clinical and aquatic Acinetobacter strains. Author(s): Guardabassi L, Dijkshoorn L, Collard JM, Olsen JE, Dalsgaard A. Source: Journal of Medical Microbiology. 2000 October; 49(10): 929-36. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11023190
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Distribution of oxytetracycline resistance plasmids between aeromonads in hospital and aquaculture environments: implication of Tn1721 in dissemination of the tetracycline resistance determinant tet A. Author(s): Rhodes G, Huys G, Swings J, McGann P, Hiney M, Smith P, Pickup RW. Source: Applied and Environmental Microbiology. 2000 September; 66(9): 3883-90. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=10966404
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Distribution of the tetracycline resistance determinant tetQ gene in oral isolates of black-pigmented anaerobes in Japan. Author(s): Okamoto M, Takano K, Maeda N. Source: Oral Microbiology and Immunology. 2001 August; 16(4): 224-8. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11442847
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Dose-dependent neuroprotective effect of ciliary neurotrophic factor delivered via tetracycline-regulated lentiviral vectors in the quinolinic acid rat model of Huntington's disease. Author(s): Regulier E, Pereira de Almeida L, Sommer B, Aebischer P, Deglon N. Source: Human Gene Therapy. 2002 November 1; 13(16): 1981-90. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12427308
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Double-blind trial of tetracycline in recurrent aphthous ulceration. Author(s): Graykowski EA, Kingman A. Source: J Oral Pathol. 1978; 7(6): 376-82. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=105096
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Dox-dependent SIVmac with tetracycline-inducible promoter in the U3 promoter region. Author(s): Xiao Y, Kuwata T, Miura T, Hayami M, Shida H. Source: Virology. 2000 April 10; 269(2): 268-75. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=10753705
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Drift of tetM determinant in urogenital microbiocenosis containing mycoplasmas during treatment with a tetracycline antibiotic. Author(s): Taraskina AE, Savicheva AM, Akopian TA, Soroka AE, Momynaliev KT, Govorun VM. Source: Bulletin of Experimental Biology and Medicine. 2002 July; 134(1): 60-3. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12459871
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Drug-induced solar urticaria due to tetracycline. Author(s): Yap LM, Foley PA, Crouch RB, Baker CS. Source: The Australasian Journal of Dermatology. 2000 August; 41(3): 181-4. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=10954992
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Effect of drug vehicle on human ocular retention of topically applied tetracycline. Author(s): Massey JY, Hanna C, Goodart R, Wallace T. Source: American Journal of Ophthalmology. 1976 February; 81(2): 151-6. Review. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=766637
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Effect of exercise on the serum level and urinary excretion of tetracycline, doxycycline and sulphamethizole. Author(s): Ylitalo P, Hinkka H, Neuvonen PJ. Source: European Journal of Clinical Pharmacology. 1977 December 16; 12(5): 367-73. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=598409
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Effectiveness of two quadruple, tetracycline- or clarithromycin-containing, secondline, Helicobacter pylori eradication therapies. Author(s): Georgopoulos SD, Ladas SD, Karatapanis S, Triantafyllou K, Spiliadi C, Mentis A, Artikis V, Raptis SA. Source: Alimentary Pharmacology & Therapeutics. 2002 March; 16(3): 569-75. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11876712
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Effects of adjunctive treatment of periodontitis with tetracycline and spiramycin. Author(s): Al-Joburi W, Quee TC, Lautar C, Iugovaz I, Bourgouin J, Delorme F, Chan EC. Source: J Periodontol. 1989 October; 60(10): 533-9. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=2681673
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Effects of metronidazole, tetracycline, and bismuth-metronidazole-tetracycline triple therapy in the Helicobacter pylori SS1 mouse model after 1 day of dosing: development of an H. pylori lead selection model. Author(s): Sizemore CF, Quispe JD, Amsler KM, Modzelewski TC, Merrill JJ, Stevenson DA, Foster LA, Slee AM. Source: Antimicrobial Agents and Chemotherapy. 2002 May; 46(5): 1435-40. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11959579
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Effects of tetracycline-controlled antisense bcl-2 expression on the growth and apoptosis of human neuroblastoma cell line SK-N-MC. Author(s): Guan J, Chen J, Zhao H. Source: Zhonghua Bing Li Xue Za Zhi. 2002 April; 31(2): 135-9. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12419161
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Efficacy and safety of single-triple capsules of bismuth biskalcitrate, metronidazole and tetracycline, given with omeprazole, for the eradication of Helicobacter pylori: an international multicentre study. Author(s): O'Morain C, Borody T, Farley A, De Boer WA, Dallaire C, Schuman R, Piotrowski J, Fallone CA, Tytgat G, Megraud F, Spenard J; International multicentre study. Source: Alimentary Pharmacology & Therapeutics. 2003 February; 17(3): 415-20. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12562455
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Efficacy of combined metronidazole and triple tetracycline therapy in the treatment of non-gonococcal urethritis. Author(s): Woolley PD, Kinghorn GR, Talbot MD, Duerden BI. Source: International Journal of Std & Aids. 1990 January; 1(1): 35-7. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=2099197
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Efficacy of oral azithromycin versus topical tetracycline in mass treatment of endemic trachoma. Author(s): Fraser-Hurt N, Bailey RL, Cousens S, Mabey D, Faal H, Mabey DC. Source: Bulletin of the World Health Organization. 2001; 79(7): 632-40. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11477966
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Efficacy of quadruple therapy with pantoprazole, bismuth, tetracycline and metronidazole as rescue treatment for Helicobacter pylori infection. Author(s): Boixeda D, Bermejo F, Martin-De-Argila C, Lopez-Sanroman A, Defarges V, Hernandez-Ranz F, Milicua JM, Garcia-Plaza A. Source: Alimentary Pharmacology & Therapeutics. 2002 August; 16(8): 1457-60. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12182745
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Emergence and rapid spread of tetracycline-resistant Vibrio cholerae strains, Madagascar. Author(s): Dromigny JA, Rakoto-Alson O, Rajaonatahina D, Migliani R, Ranjalahy J, Mauclere P. Source: Emerging Infectious Diseases. 2002 March; 8(3): 336-8. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11927038
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Enhanced expression of uridine diphosphate-N-acetylglucosaminyl transferase (OGT) in a stable, tetracycline-inducible HeLa cell line using histone deacetylase inhibitors: kinetics of cytosolic OGT accumulation and nuclear translocation. Author(s): Marshall S, Duong T, Wu T, Hering MA, Yada J, Higgins S, Orbus RJ, Yan ZH, Rumberger JM. Source: Analytical Biochemistry. 2003 August 15; 319(2): 304-13. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12871726
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Epidemiology of tetracycline resistance determinants in Shigella spp. and enteroinvasive Escherichia coli: characterization and dissemination of tet(A)-1. Author(s): Hartman AB, Essiet II, Isenbarger DW, Lindler LE. Source: Journal of Clinical Microbiology. 2003 March; 41(3): 1023-32. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12624025
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Epstein-Barr virus nuclear protein 2-induced activation of the EBV-replicative cycle in Akata cells: analysis by tetracycline-regulated expression. Author(s): Fujiwara S. Source: Curr Top Microbiol Immunol. 2001; 258: 35-50. Review. No Abstract Available. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11443866
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Eradication of Helicobacter pylori in duodenal ulcer disease tetracycline & furazolidone vs. metronidazole & amoxicillin in omeprazole based triple therapy. Author(s): Mansour-Ghanaei F, Fallah MS, Shafaghi A. Source: Medical Science Monitor : International Medical Journal of Experimental and Clinical Research. 2002 March; 8(3): Pi27-30. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11889461
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Esthetics for tetracycline stained teeth. Author(s): Eglitis II. Source: Bur. 1976 March; 77(1): 28-30. No Abstract Available. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=1065512
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Estimation of the rate of osteogenesis by tetracycline double labeling in intertrochanteric fractures of the femur in different age groups and its correlation with radiological grading of osteoporosis. Author(s): Singh S, Jain AK, Arora A, Khanna J, Bhargava SK, Kumar S. Source: Journal of Orthopaedic Science : Official Journal of the Japanese Orthopaedic Association. 2002; 7(2): 226-31. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11956983
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Evaluation of residual and therapeutic doses of tetracycline in the human-floraassociated (HFA) mice model. Author(s): Perrin-Guyomard A, Cottin S, Corpet DE, Boisseau J, Poul JM. Source: Regulatory Toxicology and Pharmacology : Rtp. 2001 October; 34(2): 125-36. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11603955
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Evaluation of the antibacterial potential of tetracycline or erythromycin mixed with calcium hydroxide as intracanal dressing against Enterococcus faecalis in vivo. Author(s): Molander A, Dahlen G. Source: Oral Surgery, Oral Medicine, Oral Pathology, Oral Radiology, and Endodontics. 2003 December; 96(6): 744-50. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=14676767
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Extended at-home bleaching of tetracycline-stained teeth with different concentrations of carbamide peroxide. Author(s): Matis BA, Wang Y, Jiang T, Eckert GJ. Source: Quintessence Int. 2002 October; 33(9): 645-55. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12666888
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Failure of chloroquine-erythromycin and chloroquine-tetracycline combinations in treatment of chloroquine-resistant falciparum malaria in eastern Thailand. Author(s): Phillips RE, Looareesuwan S, Karbwang J, Warrell DA, White NJ, Kasemsarn P, Warhurst DC. Source: Lancet. 1984 February 11; 1(8372): 300-2. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=6141378
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Failure of tetracycline therapy in early Lyme disease. Author(s): Dattwyler RJ, Halperin JJ. Source: Arthritis and Rheumatism. 1987 April; 30(4): 448-50. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=3580012
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Fatal anaphylactic reaction to tetracycline in the postoperative period. Author(s): Singh CV, Grover V, Kamra GL. Source: Anaesthesia. 1977 March; 32(3): 268-9. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=848727
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Femoral head vitality after femoral neck fracture. Comparison between pre- and peroperative tetracycline labeling. Author(s): Stromqvist B, Hansson LI. Source: Archives of Orthopaedic and Trauma Surgery. 1983; 101(4): 251-7. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=6882164
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Femoral head vitality after intracapsular hip fracture. 490 cases studied by intravital tetracycline labeling and Tc-MDP radionuclide imaging. Author(s): Stromqvist B. Source: Acta Orthop Scand Suppl. 1983; 200: 1-71. No Abstract Available. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=6223484
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Fibrin glue application in conjunction with tetracycline root conditioning and coronally positioned flap procedure in the treatment of human gingival recession defects. Author(s): Trombelli L, Scabbia A, Wikesjo UM, Calura G. Source: Journal of Clinical Periodontology. 1996 September; 23(9): 861-7. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=8891938
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Field method for the micro-quantitative determination of tetracycline in human blood serum. Author(s): Nabi SA, Abu-Nameh ES, Helaleh MI. Source: Journal of Pharmaceutical and Biomedical Analysis. 1998 June; 17(2): 357-9. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=9638589
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Fixed drug eruption due to tetracycline--a report of a case. Author(s): Armati RP. Source: The Australasian Journal of Dermatology. 1973 August; 14(2): 75-7. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=4271370
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Fixed eruption due to two unrelated drugs: oxyphenbutazone and tetracycline. Author(s): Bhargava NC, Singh G. Source: International Journal of Dermatology. 1981 July-August; 20(6): 435. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=6455387
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Fluorescent tetracycline labeling as an aid to debridement of necrotic bone in the treatment of chronic osteomyelitis. Author(s): Dahners LE, Bos GD. Source: Journal of Orthopaedic Trauma. 2002 May; 16(5): 345-6. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11972078
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Foreign body giant cell reaction related to placement of tetracycline-treated polylactic acid: report of 18 cases. Author(s): Moore JW, Brekke JH. Source: Journal of Oral and Maxillofacial Surgery : Official Journal of the American Association of Oral and Maxillofacial Surgeons. 1990 August; 48(8): 808-12. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=2197383
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Freeze-dried bone allografts combined with tetracycline in the treatment of juvenile periodontitis. Author(s): Mabry TW, Yukna RA, Sepe WW. Source: J Periodontol. 1985 February; 56(2): 74-81. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=3884767
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Frequency and distribution in the United States of strains of Neisseria gonorrhoeae with plasmid-mediated, high-level resistance to tetracycline. Author(s): Knapp JS, Zenilman JM, Biddle JW, Perkins GH, DeWitt WE, Thomas ML, Johnson SR, Morse SA. Source: The Journal of Infectious Diseases. 1987 April; 155(4): 819-22. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=3102635
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Frequency distributions of tetracycline-based measurements: implications for the interpretation of bone formation indices in the absence of double-labeled surfaces. Author(s): Foldes J, Shih MS, Parfitt AM. Source: Journal of Bone and Mineral Research : the Official Journal of the American Society for Bone and Mineral Research. 1990 October; 5(10): 1063-7. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=2080717
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Functional and histochemical analysis of MDR3 P-glycoprotein in a tetracyclinecontrolled gene expression system. Author(s): Fitscher BA, Ehehalt R, Jochims C, Pohl J, Herrmann T, Stremmel W. Source: European Journal of Medical Research. 2000 December 29; 5(12): 517-22. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11147995
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Further evidence for the role of bivalent cations in human polymorphonuclear leukocyte locomotion: recovery from tetracycline-induced inhibition in the presence of cation ionophores. Author(s): Goodhart GL. Source: J Reticuloendothel Soc. 1979 May; 25(5): 545-54. No Abstract Available. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=379329
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Gamma globulin, Evan's blue, aprotinin A PLA2 inhibitor, tetracycline and antioxidants protect epithelial cells against damage induced by synergism among streptococcal hemolysins, oxidants and proteinases: relation to the prevention of poststreptococcal sequelae and septic shock. Author(s): Ginsburg I, Sadovnic M. Source: Fems Immunology and Medical Microbiology. 1998 November; 22(3): 247-56. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=9848686
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Gastro-intestinal absorption of tetracycline hydrochloride & chloramphenicol in normal human males: effect of calcium & magnesium. Author(s): Haldar AK, Chakrabarti K, Mukherjee AK, Banerjee S. Source: Indian J Exp Biol. 1977 November; 15(11): 1043-5. No Abstract Available. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=96012
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Generalized bullous pemphigoid controlled by tetracycline therapy alone. Author(s): Pereyo NG, Davis LS. Source: Journal of the American Academy of Dermatology. 1995 January; 32(1): 138-9. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=7822510
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Generating conditional mouse mutants via tetracycline-controlled gene expression. Author(s): Schonig K, Bujard H. Source: Methods in Molecular Biology (Clifton, N.J.). 2003; 209: 69-104. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12357963
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Generation of a mammalian cell line stably expressing a tetracycline-regulated epitope-tagged human androgen receptor: implications for steroid hormone receptor research. Author(s): Wang Q, Fondell JD. Source: Analytical Biochemistry. 2001 February 15; 289(2): 217-30. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11161315
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Generation of packaging cell lines for pseudotyped retroviral vectors of the G protein of vesicular stomatitis virus by using a modified tetracycline inducible system. Author(s): Chen ST, Iida A, Guo L, Friedmann T, Yee JK. Source: Proceedings of the National Academy of Sciences of the United States of America. 1996 September 17; 93(19): 10057-62. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=8816750
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Genetic analysis of tetracycline-resistant plasmids in enteropathogenic Escherichia coli isolated from patients in Nigeria. Author(s): Daini OA, Olukoya DK, Ogunjimi AA. Source: J Diarrhoeal Dis Res. 1995 March; 13(1): 39-43. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=7657964
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Genetic basis of tetracycline resistance in clinical isolates of Listeria monocytogenes. Author(s): Poyart-Salmeron C, Trieu-Cuot P, Carlier C, MacGowan A, McLauchlin J, Courvalin P. Source: Antimicrobial Agents and Chemotherapy. 1992 February; 36(2): 463-6. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=1605611
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Genetic basis of tetracycline resistance in urogenital bacteria. Author(s): Roberts MC, Hillier SL. Source: Antimicrobial Agents and Chemotherapy. 1990 February; 34(2): 261-4. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=2327774
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Genetic characterisation of resistance to metal ions in methicillin-resistant Staphylococcus aureus: elimination of resistance to cadmium, mercury and tetracycline with loss of methicillin resistance. Author(s): Poston SM, Li Saw Hee FL. Source: Journal of Medical Microbiology. 1991 April; 34(4): 193-201. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=2020016
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Genetic mobility and distribution of tetracycline resistance determinants. Author(s): Roberts MC. Source: Ciba Found Symp. 1997; 207: 206-18; Discussion 219-22. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=9189643
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Genital Chlamydia trachomatis infections in patients with abnormal cervical smears: effect of tetracycline treatment on cell changes. Author(s): Mecsei R, Haugen OA, Halvorsen LE, Dalen A. Source: Obstetrics and Gynecology. 1989 March; 73(3 Pt 1): 317-21. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=2915857
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Giant splenic cyst with high serum concentration of CA 19-9. Failure of treatment with percutaneous transcatheter drainage and injection of tetracycline. Author(s): Yoshikane H, Suzuki T, Yoshioka N, Ogawa Y, Hayashi Y, Hamajima E, Yokoi T. Source: Scandinavian Journal of Gastroenterology. 1996 May; 31(5): 524-6. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=8734353
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Gingival fluid tetracycline release from bioerodible gels. Author(s): Maze GI, Reinhardt RA, Payne JB, Maze C, Baker RA, Bouwsma OJ, Damani NC, Fitzgerald J, Hamlin JC, Gerlach RW. Source: Journal of Clinical Periodontology. 1996 December; 23(12): 1133-6. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=8997659
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Gingival response to subgingival placement of monolithic tetracycline-impregnated fibers: microscopic observations. Author(s): Kazakos GM, Cobb CM, Morrison SL, Barker BF, Killoy WJ. Source: Int J Periodontics Restorative Dent. 1993; 13(2): 150-71. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=8360006
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Global changes in Kaposi's sarcoma-associated virus gene expression patterns following expression of a tetracycline-inducible Rta transactivator. Author(s): Nakamura H, Lu M, Gwack Y, Souvlis J, Zeichner SL, Jung JU. Source: Journal of Virology. 2003 April; 77(7): 4205-20. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12634378
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Glycylcyclines: third-generation tetracycline antibiotics. Author(s): Chopra I. Source: Current Opinion in Pharmacology. 2001 October; 1(5): 464-9. Review. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11764771
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Granulomatous rosacea treated with tetracycline. Author(s): Veien NK, Stahl D, Brodthagen H. Source: Dermatologica. 1981; 163(3): 267-9. No Abstract Available. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=6456953
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Greening of the tooth-amalgam interface during extended 10% carbamide peroxide bleaching of tetracycline-stained teeth: a case report. Author(s): Haywood VB. Source: Journal of Esthetic and Restorative Dentistry : Official Publication of the American Academy of Esthetic Dentistry . [et Al.]. 2002; 14(1): 12-7. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11915390
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Growth and development of tetracycline-resistant Chlamydia suis. Author(s): Lenart J, Andersen AA, Rockey DD. Source: Antimicrobial Agents and Chemotherapy. 2001 August; 45(8): 2198-203. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11451674
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Helicobacter pylori resistance to tetracycline. Author(s): Midolo PD, Korman MG, Turnidge JD, Lambert JR. Source: Lancet. 1996 April 27; 347(9009): 1194-5. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=8609802
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HELIDAC therapy (bismuth subsalicylate/metronidazole/tetracycline hydrochloride). Author(s): Claussen DW. Source: Gastroenterology Nursing : the Official Journal of the Society of Gastroenterology Nurses and Associates. 1997 September-October; 20(5): 188-9. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=9384064
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Hemolytic anemia after tetracycline therapy. Author(s): Simpson MB, Pryzbylik J, Innis B, Denham MA. Source: The New England Journal of Medicine. 1985 March 28; 312(13): 840-2. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=3974663
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High failure rates in outpatient treatment of salpingitis with either tetracycline alone or penicillin/ampicillin combination. Author(s): Thompson SE, Brooks C, Eschenbach DA, Spence MR, Cheng S, Sweet R, McCormack WM. Source: American Journal of Obstetrics and Gynecology. 1985 July 15; 152(6 Pt 1): 635-41. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=3895937
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High frequency of strains multiply resistant to ampicillin, trimethoprimsulfamethoxazole, streptomycin, chloramphenicol, and tetracycline isolated from patients with shigellosis in northeastern Brazil during the period 1988 to 1993. Author(s): Lima AA, Lima NL, Pinho MC, Barros Junior EA, Teixeira MJ, Martins MC, Guerrant RL. Source: Antimicrobial Agents and Chemotherapy. 1995 January; 39(1): 256-9. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=7695319
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High percentages of resistance to tetracycline and penicillin and reduced susceptibility to azithromycin characterize the majority of strain types of Neisseria gonorrhoeae isolates in Cuba, 1995-1998. Author(s): Sosa J, Ramirez-Arcos S, Ruben M, Li H, Llanes R, Llop A, Dillon JA. Source: Sexually Transmitted Diseases. 2003 May; 30(5): 443-8. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12916137
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High protective effect of a broad-spectrum sunscreen against tetracycline phototoxicity. Author(s): Duteil I, Queille-Roussel C, Rougier A, Richard A, Ortonne JP. Source: European Journal of Dermatology : Ejd. 2002 July-August; 12(4): X-Xi. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12118428
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High rate of tetracycline resistance in Streptococcus pyogenes in Iran: an epidemiological study. Author(s): Jasir A, Tanna A, Noorani A, Mirsalehian A, Efstratiou A, Schalen C. Source: Journal of Clinical Microbiology. 2000 June; 38(6): 2103-7. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=10834960
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High-dose tetracycline therapy in severe acne. Author(s): Baer RL, Leshaw SM, Shalita AR. Source: Archives of Dermatology. 1976 April; 112(4): 479-81. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=131512
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High-level tetracycline resistance in penicillinase-producing Neisseria gonorrhoeae in France. Author(s): Casin I, Perenet F, Issoire C, Riou JY, Morel P, Perol Y. Source: European Journal of Clinical Microbiology & Infectious Diseases : Official Publication of the European Society of Clinical Microbiology. 1989 October; 8(10): 92931. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=2512145
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High-level tetracycline resistance resulting from TetM in strains of Neisseria spp., Kingella denitrificans, and Eikenella corrodens. Author(s): Knapp JS, Johnson SR, Zenilman JM, Roberts MC, Morse SA. Source: Antimicrobial Agents and Chemotherapy. 1988 May; 32(5): 765-7. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=3134850
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High-level tetracycline-resistant Neisseria gonorrhoeae in Ontario, Canada-investigation of a cluster of isolates, showing chromosomally mediated resistance to penicillin combined with plasmid-mediated resistance to tetracycline. Author(s): Harnett N, Brown S, Terro R, Krishnan C, Pauze M, Yeung KH. Source: The Journal of Infectious Diseases. 1997 November; 176(5): 1269-76. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=9359728
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High-performance liquid chromatography with mass spectrometry detection for quantitating COL-3, a chemically modified tetracycline, in human plasma. Author(s): Rudek MA, March CL, Bauer KS Jr, Pluda JM, Figg WD. Source: Journal of Pharmaceutical and Biomedical Analysis. 2000 July; 22(6): 1003-14. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=10857569
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Homogeneity and long-term stability of tetracycline-regulated gene expression with low basal activity by using the rtTA2S-M2 transactivator and insulator-flanked reporter vectors. Author(s): Qu Z, Thottassery JV, Van Ginkel S, Manuvakhova M, Westbrook L, RolandLazenby C, Hays S, Kern FG. Source: Gene. 2004 February 18; 327(1): 61-73. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=14960361
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Human cell lines engineered for tetracycline-regulated expression of tumor suppressor candidate genes from a frequently affected chromosomal region, 3p21. Author(s): Protopopov AI, Li J, Winberg G, Gizatullin RZ, Kashuba VI, Klein G, Zabarovsky ER. Source: The Journal of Gene Medicine. 2002 July-August; 4(4): 397-406. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12124982
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Human monocyte response to cementum extracts from periodontally diseased teeth: effect of conditioning with tetracycline. Author(s): Shapira L, Houri Y, Barak V, Halabi A, Soskolne WA, Stabholz A. Source: J Periodontol. 1996 July; 67(7): 682-7. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=8832479
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Human organic anion transporters mediate the transport of tetracycline. Author(s): Babu E, Takeda M, Narikawa S, Kobayashi Y, Yamamoto T, Cha SH, Sekine T, Sakthisekaran D, Endou H. Source: Japanese Journal of Pharmacology. 2002 January; 88(1): 69-76. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11855680
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Human periodontal ligament fibroblast response to PDGF-BB and IGF-1 application on tetracycline HCI conditioned root surfaces. Author(s): Gamal AY, Mailhot JM, Garnick JJ, Newhouse R, Sharawy MM. Source: Journal of Clinical Periodontology. 1998 May; 25(5): 404-12. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=9650878
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Hydrothorax in continuous ambulatory peritoneal dialysis: successful treatment with intrapleural tetracycline and a review of the literature. Author(s): Benz RL, Schleifer CR. Source: American Journal of Kidney Diseases : the Official Journal of the National Kidney Foundation. 1985 February; 5(2): 136-40. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=3970020
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Hypouricemia, hypokalemia, proximal and distal tubular acidification defect following administration of outdated tetracycline: a case report. Author(s): Chusil S, Tungsanga K, Wathanavaha A, Pansin P. Source: J Med Assoc Thai. 1994 February; 77(2): 98-102. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=7798843
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Identification of a new ribosomal protection type of tetracycline resistance gene, tet(36), from swine manure pits. Author(s): Whittle G, Whitehead TR, Hamburger N, Shoemaker NB, Cotta MA, Salyers AA. Source: Applied and Environmental Microbiology. 2003 July; 69(7): 4151-8. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12839793
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Identification of tet(B), encoding high-level tetracycline resistance, in Neisseria meningitidis. Author(s): Takahashi H, Watanabe H, Kuroki T, Watanabe Y, Yamai S. Source: Antimicrobial Agents and Chemotherapy. 2002 December; 46(12): 4045-6. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12435724
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Immunoproliferative small intestinal disease in a 16-year-old boy presenting as severe malabsorption with excellent response to tetracycline treatment. Author(s): Zamir A, Parasher G, Moukarzel AA, Guarini L, Zeien L, Feldman F. Source: Journal of Clinical Gastroenterology. 1998 July; 27(1): 85-9. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=9706780
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Improving compliance with quinine + tetracycline for treatment of malaria: evaluation of health education interventions in Cambodian villages. Author(s): Denis MB. Source: Bulletin of the World Health Organization. 1998; 76 Suppl 1: 43-9. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=9763722
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In vitro activities of a new ketolide, ABT-773, alone and in combination with amoxicillin, metronidazole, or tetracycline against Helicobacter pylori. Author(s): Pendland SL, Prause JL, Neuhauser MM, Boyea N, Hackleman JM, Danziger LH. Source: Antimicrobial Agents and Chemotherapy. 2000 September; 44(9): 2518-20. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=10952605
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In vitro response to chloramphenicol, tetracycline, ampicillin, gentamicin, and betalactamase production by halophilic Vibrios from human and environmental sources. Author(s): Joseph SW, DeBell RM, Brown WP. Source: Antimicrobial Agents and Chemotherapy. 1978 February; 13(2): 244-8. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=646346
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In vitro studies on colonization resistance of the human gut microbiota to Candida albicans and the effects of tetracycline and Lactobacillus plantarum LPK. Author(s): Payne S, Gibson G, Wynne A, Hudspith B, Brostoff J, Tuohy K. Source: Curr Issues Intest Microbiol. 2003 March; 4(1): 1-8. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12691257
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In vitro synergy between ranitidine bismuth citrate and tetracycline or clarithromycin against resistant strains of Helicobacter pylori. Author(s): Midolo PD, Lambert JR, Kerr TG, Tee W. Source: European Journal of Clinical Microbiology & Infectious Diseases : Official Publication of the European Society of Clinical Microbiology. 1999 November; 18(11): 832-4. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=10614963
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In vivo manipulation of interleukin-2 expression by a retroviral tetracycline (tet)regulated system. Author(s): Pitzer C, Schindowski K, Pomer S, Wirth T, Zoller M. Source: Cancer Gene Therapy. 1999 March-April; 6(2): 139-46. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=10195880
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Incorporation rates, stabilities, cytotoxicities and release of liposomal tetracycline and doxycycline in human serum. Author(s): Sangare L, Morisset R, Omri A, Ravaoarinoro M. Source: The Journal of Antimicrobial Chemotherapy. 1998 December; 42(6): 831-4. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=10052911
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Increased tetracycline resistance in gonococci in The Netherlands. Author(s): van Klingeren B, Dessens-Kroon M, Verheuvel M. Source: Lancet. 1989 November 25; 2(8674): 1278. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=2573789
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Influence of nutritional status on plasma levels and relative bioavailability of tetracycline. Author(s): Raghuram TC, Krishnaswamy K. Source: European Journal of Clinical Pharmacology. 1977 December 2; 12(4): 281-4. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=590314
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Inhibition of proteolytic, serpinolytic, and progelatinase-b activation activities of periodontopathogens by doxycycline and the non-antimicrobial chemically modified tetracycline derivatives. Author(s): Grenier D, Plamondon P, Sorsa T, Lee HM, McNamara T, Ramamurthy NS, Golub LM, Teronen O, Mayrand D. Source: J Periodontol. 2002 January; 73(1): 79-85. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11846203
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Inhibition of trypsin-like cysteine proteinases (gingipains) from Porphyromonas gingivalis by tetracycline and its analogues. Author(s): Imamura T, Matsushita K, Travis J, Potempa J. Source: Antimicrobial Agents and Chemotherapy. 2001 October; 45(10): 2871-6. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11557483
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Intracystic tetracycline therapy for hypofunctioning cystic thyroid nodules. Author(s): Garg MK, Satija L, Khanna SK, Saini JS. Source: J Assoc Physicians India. 2000 September; 48(9): 891-4. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11198788
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Intraoperative topical tetracycline sclerotherapy following mastectomy: a prospective, randomized trial. Author(s): Rice DC, Morris SM, Sarr MG, Farnell MB, van Heerden JA, Grant CS, Rowland CM, Ilstrup DM, Donohue JH. Source: Journal of Surgical Oncology. 2000 April; 73(4): 224-7. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=10797336
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Intrapleural therapy with tetracycline and lidocaine for malignant pleural effusions. Author(s): Wallach HW. Source: Chest. 1978 February; 73(2): 246. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=620597
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Intra-pocket antibiotic therapy using resorbable and non-resorbable slow-release devices containing tetracycline. Author(s): Minabe M, Suzuki F, Umemoto T. Source: Periodontal Clin Investig. 2000; 22(1): 14-21. Review. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11402456
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In-vitro anti-chlamydial activities of free and liposomal tetracycline and doxycycline. Author(s): Sangare L, Morisset R, Ravaoarinoro M. Source: Journal of Medical Microbiology. 1999 July; 48(7): 689-93. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=10403420
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Isolation and characterization of tetracycline-resistant clinical isolates of Helicobacter pylori. Author(s): Kwon DH, Kim JJ, Lee M, Yamaoka Y, Kato M, Osato MS, El-Zaatari FA, Graham DY. Source: Antimicrobial Agents and Chemotherapy. 2000 November; 44(11): 3203-5. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11036054
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Killing effect of TNF-related apoptosis inducing ligand regulated by tetracycline on gastric cancer cell line NCI-N87. Author(s): Wei XC, Wang XJ, Chen K, Zhang L, Liang Y, Lin XL. Source: World Journal of Gastroenterology : Wjg. 2001 August; 7(4): 559-62. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11819829
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Lack of association between first myocardial infarction and past use of erythromycin, tetracycline, or doxycycline. Author(s): Jackson LA, Smith NL, Heckbert SR, Grayston JT, Siscovick DS, Psaty BM. Source: Emerging Infectious Diseases. 1999 March-April; 5(2): 281-4. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=10221884
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Lack of cross-sensitivity between tetracycline, doxycycline, and minocycline with regard to fixed drug sensitivity to tetracycline. Author(s): Bargman H. Source: Journal of the American Academy of Dermatology. 1984 November; 11(5 Pt 1): 900-2. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=6239882
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Lactic acidosis and Fanconi's syndrome due to degraded tetracycline. Author(s): Montoliu J, Carrera M, Darnell A, Revert L. Source: British Medical Journal (Clinical Research Ed.). 1981 December 12; 283(6306): 1576-7. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=6796174
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Laminates--a practical approach to restoring tetracycline-stained teeth. Author(s): Paterson JR, Anson RA. Source: Pediatr Dent. 1980 December; 2(4): 300-3. No Abstract Available. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=6941008
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Large symptomatic mullerian duct cyst treated by tetracycline sclerotherapy. Author(s): Ahmed M, Palmer JW. Source: International Urology and Nephrology. 1995; 27(2): 193-7. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=7591578
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Legionella bozemanii pneumonia and tetracycline. Author(s): Ruiz-Santana S, Aguado-Bourrey JM, Narvaez-Bermejo JM, GonzalezMediero G. Source: Annals of Internal Medicine. 1986 December; 105(6): 969-70. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=3777724
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Leukemoid blood reaction to tetracycline. Author(s): Chatham WW, Ross DW. Source: Southern Medical Journal. 1983 September; 76(9): 1195-6. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=6612406
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Lichen planus pemphigoides: combination therapy with tetracycline and nicotinamide. Author(s): Fivenson DP, Kimbrough TL. Source: Journal of the American Academy of Dermatology. 1997 April; 36(4): 638-40. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=9092758
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Life on a string: development of the tetracycline fiber delivery system. Author(s): Goodson JM. Source: Technology and Health Care : Official Journal of the European Society for Engineering and Medicine. 1996 September; 4(3): 269-82. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=8931237
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Linear IgA bullous dermatosis: successful treatment with tetracycline and nicotinamide. Author(s): Peoples D, Fivenson DP. Source: Journal of the American Academy of Dermatology. 1992 March; 26(3 Pt 2): 498-9. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=1532966
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Liquid chromatographic and flow injection analysis of tetracycline using sensitized europium (III) luminescence detection. Author(s): Wenzel TJ, Collette LM, Dahlen DT, Hendrickson SM, Yarmaloff LW. Source: Journal of Chromatography. 1988 December 9; 433: 149-58. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=3235543
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Local delivery of tetracycline: from concept to clinical application. Author(s): Tonetti MS. Source: Journal of Clinical Periodontology. 1998 November; 25(11 Pt 2): 969-77. Review. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=9839855
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Local tetracycline therapy of the periodontium during orthodontic treatment. Author(s): Hoerman KC, Lang RL, Klapper L, Beery J. Source: Quintessence Int. 1985 February; 16(2): 161-6. No Abstract Available. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=3857661
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Long-term effect of tetracycline fibers on recurrent lesions in periodontal maintenance patients. Author(s): Corsair A. Source: Periodontal Clin Investig. 1994 Spring; 16(1): 8-13. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=9055682
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Long-term prognosis of intentional endodontics and internal bleaching of tetracycline-stained teeth. Author(s): Abou-Rass M. Source: Compend Contin Educ Dent. 1998 October; 19(10): 1034-8, 1040-2, 1044 Passim. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=10371886
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Long-term results after tetracycline pleurodesis in spontaneous pneumothorax. Author(s): Olsen PS, Andersen HO. Source: The Annals of Thoracic Surgery. 1992 June; 53(6): 1015-7. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=1596120
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Long-term tetracycline use in the treatment of acne vulgaris--the role of routine laboratory monitoring] Author(s): Tanzman ES. Source: Journal of American College Health : J of Ach. 1988 March; 36(5): 272-3, 276-8. Review. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=2964465
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Long-term use of tetracycline. Author(s): Bhagavan BS, Wenk RE, McCarthy EF, Gebhardt FC, Lustgarten JA. Source: Jama : the Journal of the American Medical Association. 1982 May 28; 247(20): 2780. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=7077774
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Low-dose minocycline therapy in tetracycline-recalcitrant acne vulgaris. Author(s): Cullen SI. Source: Cutis; Cutaneous Medicine for the Practitioner. 1978 January; 21(1): 101-4. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=146595
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Lyme-disease meningitis treated with tetracycline. Author(s): Ackley A Jr, Lupovici M. Source: Annals of Internal Medicine. 1986 October; 105(4): 630-1. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=3752778
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Macrolide and tetracycline resistance and molecular relationships of clinical strains of Streptococcus agalactiae. Author(s): Culebras E, Rodriguez-Avial I, Betriu C, Redondo M, Picazo JJ. Source: Antimicrobial Agents and Chemotherapy. 2002 May; 46(5): 1574-6. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11959603
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Management of hepatic cysts by percutaneous drainage and instillation of tetracycline hydrochloride. Author(s): McFarlane ME, Venugopal R, McDonald A, Ewing R, Newnham MS, Johnson L. Source: The West Indian Medical Journal. 2001 September; 50(3): 230-3. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11769033
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Meta-analysis of local tetracycline in treating chronic periodontitis. Author(s): Pavia M, Nobile CG, Angelillo IF. Source: J Periodontol. 2003 June; 74(6): 916-32. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12887006
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Mild pemphigus foliaceus responding to combination therapy with niacinamide and tetracycline. Author(s): Chen S, Lu X, Zhou G. Source: International Journal of Dermatology. 2003 December; 42(12): 981-2. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=14636199
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Minocycline and other tetracycline derivatives: a neuroprotective strategy in Parkinson's disease and Huntington's disease. Author(s): Thomas M, Le WD, Jankovic J. Source: Clinical Neuropharmacology. 2003 January-February; 26(1): 18-23. Review. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12567160
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Minocycline, tetracycline and furazolidone in the treatment of cholera. Author(s): Mazumdar DN, De S, De SP, Sircar BK. Source: The Indian Journal of Medical Research. 1977 December; 66(6): 917-21. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=611110
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Minocycline-induced activation of tetracycline-responsive promoter. Author(s): Chtarto A, Tenenbaum L, Velu T, Brotchi J, Levivier M, Blum D. Source: Neuroscience Letters. 2003 December 11; 352(3): 155-8. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=14625008
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Mitochondria as the site of action of tetracycline on Plasmodium falciparum. Author(s): Kiatfuengfoo R, Suthiphongchai T, Prapunwattana P, Yuthavong Y. Source: Molecular and Biochemical Parasitology. 1989 May 1; 34(2): 109-15. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=2651921
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Modulation of myosin A expression by a newly established tetracycline repressorbased inducible system in Toxoplasma gondii. Author(s): Meissner M, Brecht S, Bujard H, Soldati D. Source: Nucleic Acids Research. 2001 November 15; 29(22): E115. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11713335
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Molecular epidemiology of Neisseria gonorrheae isolates with plasmid-mediated tetracycline resistance in Canada: temporal and geographical trends (1986-1997). Author(s): Greco V, Ng LK, Catana R, Li H, Dillon JA. Source: Microbial Drug Resistance (Larchmont, N.Y.). 2003 Winter; 9(4): 353-60. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=15000741
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Molecular surveillance of macrolide, tetracycline and quinolone resistance mechanisms in 1191 clinical European Streptococcus pneumoniae isolates. Author(s): Schmitz FJ, Perdikouli M, Beeck A, Verhoef J, Fluit AC. Source: International Journal of Antimicrobial Agents. 2001 November; 18(5): 433-6. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11711257
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Mutations in the 16S rRNA genes of Helicobacter pylori mediate resistance to tetracycline. Author(s): Trieber CA, Taylor DE. Source: Journal of Bacteriology. 2002 April; 184(8): 2131-40. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11914344
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Nasopharyngeal carriage of Staphylococcus aureus and carriage of tetracyclineresistant strains associated with HIV-seropositivity. Author(s): Amir M, Paul J, Batchelor B, Kariuki S, Ojoo J, Waiyaki P, Gilks C. Source: European Journal of Clinical Microbiology & Infectious Diseases : Official Publication of the European Society of Clinical Microbiology. 1995 January; 14(1): 34-40. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=7729450
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Neurite outgrowth can be modulated in vitro using a tetracycline-repressible gene therapy vector expressing human nerve growth factor. Author(s): Blesch A, Uy HS, Diergardt N, Tuszynski MH. Source: Journal of Neuroscience Research. 2000 February 1; 59(3): 402-9. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=10679776
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New developments in tetracycline antibiotics: glycylcyclines and tetracycline efflux pump inhibitors. Author(s): Chopra I. Source: Drug Resistance Updates : Reviews and Commentaries in Antimicrobial and Anticancer Chemotherapy. 2002 July-August; 5(3-4): 119-25. Review. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12237079
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Nightguard vital bleaching of tetracycline-stained teeth: 54 months post treatment. Author(s): Leonard RH Jr, Haywood VB, Eagle JC, Garland GE, Caplan DJ, Matthews KP, Tart ND. Source: J Esthet Dent. 1999; 11(5): 265-77. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=10825882
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Nightguard vital bleaching of tetracycline-stained teeth: 90 months post treatment. Author(s): Leonard RH Jr, Van Haywood B, Caplan DJ, Tart ND. Source: Journal of Esthetic and Restorative Dentistry : Official Publication of the American Academy of Esthetic Dentistry . [et Al.]. 2003; 15(3): 142-52; Discussion 153. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12859112
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Nodulocystic acne: oral gugulipid versus tetracycline. Author(s): Thappa DM, Dogra J. Source: The Journal of Dermatology. 1994 October; 21(10): 729-31. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=7798429
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Nondiseased dentinal root surface following citric acid or tetracycline hydrochloride conditioning: a scanning electron microscopic study on the effects of ultrasonic irrigation before and after root conditioning. Author(s): Babay N. Source: Quintessence Int. 1997 February; 28(2): 93-7. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=10332361
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Novel retroviral vector transferring a suicide gene and a selectable marker gene with enhanced gene expression by using a tetracycline-responsive expression system. Author(s): Hwang JJ, Scuric Z, Anderson WF. Source: Journal of Virology. 1996 November; 70(11): 8138-41. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=8892941
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Novel tetracycline resistance determinant from the oral metagenome. Author(s): Diaz-Torres ML, McNab R, Spratt DA, Villedieu A, Hunt N, Wilson M, Mullany P. Source: Antimicrobial Agents and Chemotherapy. 2003 April; 47(4): 1430-2. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12654685
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Novel tetracycline resistance gene, tet(32), in the Clostridium-related human colonic anaerobe K10 and its transmission in vitro to the rumen anaerobe Butyrivibrio fibrisolvens. Author(s): Melville CM, Scott KP, Mercer DK, Flint HJ. Source: Antimicrobial Agents and Chemotherapy. 2001 November; 45(11): 3246-9. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11600392
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Occurrence of the new tetracycline resistance gene tet(W) in bacteria from the human gut. Author(s): Scott KP, Melville CM, Barbosa TM, Flint HJ. Source: Antimicrobial Agents and Chemotherapy. 2000 March; 44(3): 775-7. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=10681357
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Omeprazole plus clarithromycin and either tinidazole or tetracycline for Helicobacter pylori infection: a randomized prospective study. Author(s): Zullo A, Rinaldi V, Pugliano F, Diana F, Attili AF. Source: The American Journal of Gastroenterology. 1997 November; 92(11): 2029-31. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=9362185
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Omeprazole, furazolidone, and tetracycline: an eradication treatment for resistant H. pylori in Brazilian patients with peptic ulcer disease. Author(s): Silva FM, Eisig JN, Chehter EZ, Silva JJ, Laudanna AA. Source: Revista Do Hospital Das Clinicas. 2002 September-October; 57(5): 205-8. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12436176
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One-week regimens containing ranitidine bismuth citrate, furazolidone and either amoxicillin or tetracycline effectively eradicate Helicobacter pylori: a multicentre, randomized, double-blind study. Author(s): Lu H, Zhang DZ, Hu PJ, Li ZS, Lu XH, Fang XC, Xiao SD. Source: Alimentary Pharmacology & Therapeutics. 2001 December; 15(12): 1975-9. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11736729
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Operational comparison of single-dose azithromycin and topical tetracycline for trachoma. Author(s): Bowman RJ, Sillah A, Van Dehn C, Goode VM, Muquit M, Johnson GJ, Milligan P, Rowley J, Faal H, Bailey RL. Source: Investigative Ophthalmology & Visual Science. 2000 December; 41(13): 4074-9. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11095598
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Optical fiber sensor for tetracycline antibiotics based on fluorescence quenching of covalently immobilized anthracene. Author(s): Liu W, Wang Y, Tang J, Shen G, Yu R. Source: The Analyst. 1998 February; 123(2): 365-9. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=9579089
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Optimization of a novel bioerodible device based on auto-catalyzed poly(ortho esters) for controlled delivery of tetracycline to periodontal pocket. Author(s): Schwach-Abdellaoui K, Monti A, Barr J, Heller J, Gurny R. Source: Biomaterials. 2001 June; 22(12): 1659-66. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11374468
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Oral tetracycline rinse improves symptoms of white sponge nevus. Author(s): Lim J, Ng SK. Source: Journal of the American Academy of Dermatology. 1992 June; 26(6): 1003-5. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=1607397
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Osteoblast proliferation and differentiation on dentin slices are modulated by pretreatment of the surface with tetracycline or osteoclasts. Author(s): Schwartz Z, Lohmann CH, Wieland M, Cochran DL, Dean DD, Textor M, Bonewald LF, Boyan BD. Source: J Periodontol. 2000 April; 71(4): 586-97. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=10807123
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Overdose of tetracycline for pleurodesis leading to chemical burns of the pleura. Author(s): Chaugle H, Parchment C, Keenan DJ, Grotte GJ. Source: European Journal of Cardio-Thoracic Surgery : Official Journal of the European Association for Cardio-Thoracic Surgery. 1999 October; 16(4): 469-70. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=10571097
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PCR monitoring for tetracycline resistance genes in subgingival plaque following site-specific periodontal therapy. A preliminary report. Author(s): Manch-Citron JN, Lopez GH, Dey A, Rapley JW, MacNeill SR, Cobb CM. Source: Journal of Clinical Periodontology. 2000 June; 27(6): 437-46. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=10883874
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Pharmacokinetic interaction of tetracycline with centchroman in healthy female volunteers. Author(s): Khurana M, Lal J, Kamboj VP, Nityanand S, Gupta RC. Source: Drugs in R&D. 2003; 4(5): 293-9. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12952498
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Phenotypic and molecular characterization of tetracycline- and erythromycin-resistant strains of Streptococcus pneumoniae. Author(s): Montanari MP, Cochetti I, Mingoia M, Varaldo PE. Source: Antimicrobial Agents and Chemotherapy. 2003 July; 47(7): 2236-41. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12821474
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Porphyria-like cutaneous changes induced by tetracycline hydrochloride photosensitization. Author(s): Epstein JH, Seibert JS. Source: Archives of Dermatology. 1976 May; 112(5): 661-6. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=132139
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Possible nitrosodimethylamine formation in comparative in vitro nitrosation experiments with six different tetracycline antibiotics. Author(s): Roper H, Heyns K. Source: Iarc Sci Publ. 1978; (19): 219-37. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=680727
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Prevalence and identification of tetracycline-resistant oral bacteria in children not receiving antibiotic therapy. Author(s): Lancaster H, Ready D, Mullany P, Spratt D, Bedi R, Wilson M. Source: Fems Microbiology Letters. 2003 November 7; 228(1): 99-104. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=14612243
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Prevalence of macrolide and tetracycline resistance mechanisms in Streptococcus pyogenes isolates and in vitro susceptibility to telithromycin. Author(s): Betriu C, Culebras E, Redondo M, Rodriguez-Avial I, Gomez M, Boloix A, Picazo JJ. Source: The Journal of Antimicrobial Chemotherapy. 2002 September; 50(3): 436-8. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12205076
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Prevalence of tetracycline resistance genes in oral bacteria. Author(s): Villedieu A, Diaz-Torres ML, Hunt N, McNab R, Spratt DA, Wilson M, Mullany P. Source: Antimicrobial Agents and Chemotherapy. 2003 March; 47(3): 878-82. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12604515
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Pseudotumor cerebri, a rare adverse reaction to tetracycline therapy. A case report. Author(s): Minutello JS, Dimayuga RG, Carter J. Source: J Periodontol. 1988 December; 59(12): 848-51. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=3225732
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Pulsating fixed drug eruption due to tetracycline. Author(s): Parish LC, Witkowski JA. Source: Acta Dermato-Venereologica. 1978; 58(6): 545-7. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=83083
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Quadruple therapy containing amoxicillin and tetracycline is an effective regimen to rescue failed triple therapy by overcoming the antimicrobial resistance of Helicobacter pylori. Author(s): Chi CH, Lin CY, Sheu BS, Yang HB, Huang AH, Wu JJ. Source: Alimentary Pharmacology & Therapeutics. 2003 August 1; 18(3): 347-53. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12895220
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Quality assessment and meta-analysis of systemic tetracycline use in chronic adult periodontitis. Author(s): Hayes C, Antczak-Bouckoms A, Burdick E. Source: Journal of Clinical Periodontology. 1992 March; 19(3): 164-8. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=1532607
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Quantitation of antibiotics using high-pressure liquid chromatography: tetracycline. Author(s): Nilsson-Ehle I, Yoshikawa TT, Schotz MC, Guze LB. Source: Antimicrobial Agents and Chemotherapy. 1976 May; 9(5): 754-60. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=821388
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Quinine with tetracycline for the treatment of drug-resistant falciparum malaria in Thailand. Author(s): Watt G, Loesuttivibool L, Shanks GD, Boudreau EF, Brown AE, Pavanand K, Webster HK, Wechgritaya S. Source: The American Journal of Tropical Medicine and Hygiene. 1992 July; 47(1): 10811. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=1636876
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Quinine-tetracycline and quinine-bactrim treatment of acute falciparum malaria in Thailand. Author(s): Colwell EJ, Hickman RL, Kosakal S. Source: Annals of Tropical Medicine and Parasitology. 1973 June; 67(2): 125-32. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=4578933
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Quinine-tetracycline for multidrug resistant falciparum malaria. Author(s): Bunnag D, Karbwang J, Na-Bangchang K, Thanavibul A, Chittamas S, Harinasuta T. Source: Southeast Asian J Trop Med Public Health. 1996 March; 27(1): 15-8. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=9031393
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Quiz of the month. Biopsy of the posterior iliac crest after double tetracycline labeling revealed osteomalacia. Author(s): Norris SH. Source: American Journal of Nephrology. 1987; 7(1): 44, 84. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=3578374
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Reduced susceptibility to azithromycin and high percentages of penicillin and tetracycline resistance in Neisseria gonorrhoeae isolates from Manaus, Brazil, 1998. Author(s): Dillon JA, Rubabaza JP, Benzaken AS, Sardinha JC, Li H, Bandeira MG, dos Santos Fernando Filho E. Source: Sexually Transmitted Diseases. 2001 September; 28(9): 521-6. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11518869
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Refractory chronic periodontitis: effect of oral tetracycline hydrochloride and root planning. Author(s): Papli R, Lewis JM. Source: Aust Dent J. 1989 February; 34(1): 60-8. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=2705941
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Relative safety of long-term administration of tetracycline in acne vulgaris. Author(s): Akers WA, Maibach HI. Source: Cutis; Cutaneous Medicine for the Practitioner. 1976 March; 17(3): 531-4. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=138547
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Release kinetics of 25% tetracycline hydrochloride-loaded ethylene vinyl acetate fibers. Author(s): Demirel K, Yalcin F, Polat E, Onan U, Meric H, Altas K. Source: Periodontal Clin Investig. 1999; 21(1): 6-9. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11811177
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Requirement of cell growth for gene expression induced by the lactose and tetracycline repressor-operator combination system in a human T cell line. Author(s): Iwanaga R, Ohtani K, Nakamura M. Source: Biochemical and Biophysical Research Communications. 2000 September 24; 276(2): 546-52. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11027511
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Resistance of Helicobacter pylori isolated in Israel to metronidazole, clarithromycin, tetracycline, amoxicillin and cefixime. Author(s): Samra Z, Shmuely H, Niv Y, Dinari G, Passaro DJ, Geler A, Gal E, Fishman M, Bachor J, Yahav J. Source: The Journal of Antimicrobial Chemotherapy. 2002 June; 49(6): 1023-6. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12039897
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Resistance to tetracycline and distribution of tetracycline resistance genes in European Staphylococcus aureus isolates. Author(s): Schmitz FJ, Krey A, Sadurski R, Verhoef J, Milatovic D, Fluit AC; European SENTRY Participants. Source: The Journal of Antimicrobial Chemotherapy. 2001 February; 47(2): 239-40. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11157916
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Resistance to tetracycline, macrolide-lincosamide-streptogramin, trimethoprim, and sulfonamide drug classes. Author(s): Roberts MC. Source: Molecular Biotechnology. 2002 March; 20(3): 261-83. Review. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11936257
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Reversible sideroblastic anemia associated with the tetracycline analogue COL-3. Author(s): Rudek MA, Horne M, Figg WD, Dahut W, Dyer V, Pluda JM, Reed E. Source: American Journal of Hematology. 2001 May; 67(1): 51-3. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11279658
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Robust and efficient regulation of transgene expression in vivo by improved tetracycline-dependent lentiviral vectors. Author(s): Vigna E, Cavalieri S, Ailles L, Geuna M, Loew R, Bujard H, Naldini L. Source: Molecular Therapy : the Journal of the American Society of Gene Therapy. 2002 March; 5(3): 252-61. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11863414
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Seal finger--tetracycline is first line. Author(s): Hartley JW, Pitcher D. Source: The Journal of Infection. 2002 August; 45(2): 71-5. Review. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12217706
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SEM study on the effect of two different demineralization methods with saturated tetracycline hydrochloride on diseased root surfaces. Author(s): Babay N. Source: The Journal of Contemporary Dental Practice [electronic Resource]. 2001 May 15; 2(2): 25-35. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12167931
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Spread of erythromycin-, tetracycline-, and aminoglycoside-resistant genes in methicillin-resistant Staphylococcus aureus clinical isolates in a Kumamoto Hospital. Author(s): Sekiguchi J, Fujino T, Saruta K, Kawano F, Takami J, Miyazaki H, Kuratsuji T, Yoshikura H, Kirikae T. Source: Japanese Journal of Infectious Diseases. 2003 June; 56(3): 133-7. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12944686
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Structure and function in rhodopsin: a tetracycline-inducible system in stable mammalian cell lines for high-level expression of opsin mutants. Author(s): Reeves PJ, Kim JM, Khorana HG. Source: Proceedings of the National Academy of Sciences of the United States of America. 2002 October 15; 99(21): 13413-8. Epub 2002 Oct 07. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12370422
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Structure and function in rhodopsin: high-level expression of rhodopsin with restricted and homogeneous N-glycosylation by a tetracycline-inducible Nacetylglucosaminyltransferase I-negative HEK293S stable mammalian cell line. Author(s): Reeves PJ, Callewaert N, Contreras R, Khorana HG. Source: Proceedings of the National Academy of Sciences of the United States of America. 2002 October 15; 99(21): 13419-24. Epub 2002 Oct 07. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12370423
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Subgingival administration of tetracycline on a collagen film. Author(s): Minabe M, Takeuchi K, Tamura T, Hori T, Umemoto T. Source: J Periodontol. 1989 October; 60(10): 552-6. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=2810009
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Susceptibilities of Campylobacter jejuni isolates from Germany to ciprofloxacin, moxifloxacin, erythromycin, clindamycin, and tetracycline. Author(s): Wagner J, Jabbusch M, Eisenblatter M, Hahn H, Wendt C, Ignatius R. Source: Antimicrobial Agents and Chemotherapy. 2003 July; 47(7): 2358-61. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12821499
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Susceptibilities of Eikenella corrodens, Prevotella intermedia, and Prevotella nigrescens clinical isolates to amoxicillin and tetracycline. Author(s): Luong N, Tsai J, Chen C. Source: Antimicrobial Agents and Chemotherapy. 2001 November; 45(11): 3253-5. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11600394
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Switching off HER-2/neu in a tetracycline-controlled mouse tumor model leads to apoptosis and tumor-size-dependent remission. Author(s): Schiffer IB, Gebhard S, Heimerdinger CK, Heling A, Hast J, Wollscheid U, Seliger B, Tanner B, Gilbert S, Beckers T, Baasner S, Brenner W, Spangenberg C, Prawitt D, Trost T, Schreiber WG, Zabel B, Thelen M, Lehr HA, Oesch F, Hengstler JG. Source: Cancer Research. 2003 November 1; 63(21): 7221-31. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=14612517
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Synergistic bactericidal effects of acrinol and tetracycline against Pseudomonas aeruginosa. Author(s): Saji M, Fujii K, Ohkuni H, Irie N, Osono E, Kato F. Source: Journal of Infection and Chemotherapy : Official Journal of the Japan Society of Chemotherapy. 2000 June; 6(2): 86-92. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11810541
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Tetracycline in the treatment of cholera caused by Vibrio cholerae O1 resistant to the drug in vitro. Author(s): Khan AM, von Gierke U, Hossain MS, Fuchs GJ. Source: J Health Popul Nutr. 2003 March; 21(1): 76-8. No Abstract Available. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12751678
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Tetracycline therapy: update. Author(s): Roberts MC. Source: Clinical Infectious Diseases : an Official Publication of the Infectious Diseases Society of America. 2003 February 15; 36(4): 462-7. Epub 2003 January 28. Review. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12567304
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Tetracycline-dependent regulation of formamidopyrimidine DNA glycosylase in transgenic mice conditionally reduces oxidative DNA damage in vivo. Author(s): Laposa RR, Henderson JT, Wells PG. Source: The Faseb Journal : Official Publication of the Federation of American Societies for Experimental Biology. 2003 July; 17(10): 1343-5. Epub 2003 May 20. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12759334
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Tetracycline-inducible transgene expression mediated by a single AAV vector. Author(s): Chtarto A, Bender HU, Hanemann CO, Kemp T, Lehtonen E, Levivier M, Brotchi J, Velu T, Tenenbaum L. Source: Gene Therapy. 2003 January; 10(1): 84-94. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12525840
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Tetracycline-regulated gene expression in replication-incompetent herpes simplex virus vectors. Author(s): Schmeisser F, Donohue M, Weir JP. Source: Human Gene Therapy. 2002 December 10; 13(18): 2113-24. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12542843
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Tetracycline-regulated secretion of human insulin in a transfected non-endocrine cell line. Author(s): Scougall KT, Maltin CA, Shaw JA. Source: Journal of Molecular Endocrinology. 2003 June; 30(3): 331-46. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12790803
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Tetracycline-regulated secretion of human insulin in transfected primary myoblasts. Author(s): Scougall KT, Shaw JA. Source: Biochemical and Biophysical Research Communications. 2003 April 25; 304(1): 167-75. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12705902
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The effect of tetracycline hydrochloride on the attachment of gingival fibroblasts. A scanning electron microscopic study on the effect of ultrasonic scaling before root conditioning. Author(s): Babay N. Source: Odontostomatol Trop. 2002 December; 25(100): 13-7. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12680130
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The use of tetracycline fibres in the treatment of generalised aggressive periodontitis: clinical and microbiological findings. Author(s): Sakellari D, Vouros I, Konstantinidis A. Source: J Int Acad Periodontol. 2003 April; 5(2): 52-60. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12760507
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Treatment of endemic fluorosis and tetracycline staining with macroabrasion and nightguard vital bleaching: a case report. Author(s): Bodden MK, Haywood VB. Source: Quintessence Int. 2003 February; 34(2): 87-91. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12666856
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Ultrastructural changes of the tooth root surface by Nd:YAG laser irradiation followed by citric acid and tetracycline. Author(s): Jeng JH, Chen KW, Lin CP, Chou HG, Lan WH. Source: J Formos Med Assoc. 1999 April; 98(4): 242-7. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=10389367
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Undernutrition and tetracycline half life. Author(s): Shastri RA, Krishnaswamy K. Source: Clinica Chimica Acta; International Journal of Clinical Chemistry. 1976 January 16; 66(2): 157-64. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=1245065
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Uptake of tetracycline by aortic aneurysm wall and its effect on inflammation and proteolysis. Author(s): Franklin IJ, Harley SL, Greenhalgh RM, Powell JT. Source: The British Journal of Surgery. 1999 June; 86(6): 771-5. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=10383577
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Use of a recombinant parvovirus to facilitate screening for human melanoma cell clones expressing tetracycline-responsive transactivators. Author(s): Pacheco TR, Maxwell F, Wu MF, Na S, Maxell IH. Source: Gene. 1999 March 18; 229(1-2): 125-9. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=10336332
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Use of tetracycline as an inhibitor of matrix metalloproteinase activity secreted by human bone-metastasizing cancer cells. Author(s): Duivenvoorden WC, Hirte HW, Singh G. Source: Invasion & Metastasis. 1997; 17(6): 312-22. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=9949290
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Use of tetracycline fibre to treat localized unstable periodontitis. Author(s): Carlson-Mann LD. Source: Probe. 1995 July-August; 29(4): 150-1. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=9518781
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Use of tetracycline-controlled gene expression systems to study mammalian cell cycle. Author(s): Freundlieb S, Baron U, Bonin AL, Gossen M, Bujard H. Source: Methods Enzymol. 1997; 283: 159-73. No Abstract Available. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=9251018
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Use of the human EF-1alpha promoter for expression can significantly increase success in establishing stable cell lines with consistent expression: a study using the tetracycline-inducible system in human cancer cells. Author(s): Gopalkrishnan RV, Christiansen KA, Goldstein NI, DePinho RA, Fisher PB. Source: Nucleic Acids Research. 1999 December 15; 27(24): 4775-82. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=10572178
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Use of the polymeric matrix as internal standard for quantitation of in vivo delivery of tetracycline HCl from Actisite tetracycline fiber during periodontal treatment. Author(s): Litch JM, Encarnacion M, Chen S, Leonard J, Burkoth TL. Source: Journal of Periodontal Research. 1996 November; 31(8): 540-4. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=8971652
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Using oral tetracycline and topical betamethasone valerate to treat acrodermatitis continua of hallopeau. Author(s): Piquero-Casals J, Fonseca de Mello AP, Dal Coleto C, Fonseca Takahashi MD, Simonsen Nico MM. Source: Cutis; Cutaneous Medicine for the Practitioner. 2002 August; 70(2): 106-8. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12234156
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Variation in comedonal antibiotic concentrations following application of topical tetracycline for acne vulgaris. Author(s): Gardner KJ, Cunliffe WJ, Eady EA, Cove JH. Source: The British Journal of Dermatology. 1994 November; 131(5): 649-54. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=7999595
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Vascularity of the femoral head. Tc diphosphonate scintigraphy validated with tetracycline labeling. Author(s): D'Ambrosia RD, Riggins RS, Stadalnik RC, DeNardo GL. Source: Clinical Orthopaedics and Related Research. 1976 November-December; (121): 143-8. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=991494
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Vascularity of the femoral head: 18fluorine scintigraphy validated with tetracycline labeling. Author(s): Stadalnik RC, Riggins RL, D'Ambrosia R, DeNardo GL. Source: Radiology. 1975 March; 114(3): 663-6. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=1118569
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Vibrio cholerae in the horn of Africa: epidemiology, plasmids, tetracycline resistance gene amplification, and comparison between O1 and non-O1 strains. Author(s): Coppo A, Colombo M, Pazzani C, Bruni R, Mohamud KA, Omar KH, Mastrandrea S, Salvia AM, Rotigliano G, Maimone F. Source: The American Journal of Tropical Medicine and Hygiene. 1995 October; 53(4): 351-9. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=7485686
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Vital bleaching of tetracycline-stained permanent teeth. Author(s): Fenton SJ. Source: W V Dent J. 1979 April; 53(2): 7-10. No Abstract Available. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=296862
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Vitality of the femoral head after femoral neck fracture evaluated by tetracycline labeling. Author(s): Stromqvist B, Ceder L, Hansson LI, Thorngren KG. Source: Archives of Orthopaedic and Trauma Surgery. 1981; 99(1): 1-6. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=7316696
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Vitality of the slipped capital femoral epiphysis. Preoperative evaluation by tetracycline labeling. Author(s): Hagglund G, Hansson LI, Ordeberg G. Source: Acta Orthopaedica Scandinavica. 1985 June; 56(3): 215-7. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=4036569
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White sponge naevus successfully treated with tetracycline mouth rinse. Author(s): Becker LR, Lutz C, Erbard H, Brocker EB, Hamm H. Source: Acta Dermato-Venereologica. 1997 September; 77(5): 413. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=9298153
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White sponge naevus successfully treated with topical tetracycline. Author(s): McDonagh AJ, Gawkrodger DJ, Walker AE. Source: Clinical and Experimental Dermatology. 1990 March; 15(2): 152-3. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=2347109
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Why now? Use of tetracycline in young children. Author(s): Yeager AS. Source: Jama : the Journal of the American Medical Association. 1977 May 9; 237(19): 2101. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=576894
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Worldwide distribution of the conjugative Clostridium perfringens tetracycline resistance plasmid, pCW3. Author(s): Abraham LJ, Wales AJ, Rood JI. Source: Plasmid. 1985 July; 14(1): 37-46. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=2863833
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Xenobiotic response in humanized double transgenic mice expressing tetracyclinecontrolled transactivator and human CYP1B1. Author(s): Hwang DY, Chae KR, Shin DH, Hwang JH, Lim CH, Kim YJ, Kim BJ, Goo JS, Shin YY, Jang IS, Cho JS, Kim YK. Source: Archives of Biochemistry and Biophysics. 2001 November 1; 395(1): 32-40. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11673863
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X-ray microbeam diffraction analyses on a tooth discolored by tetracycline. Author(s): Nonomura E, Okamoto M, Sobue S, Moriwaki Y. Source: Journal of Dental Research. 1977 April; 56(4): 447. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=265979
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Yellow lunulae with fluorescence after tetracycline therapy. Author(s): Hendricks AA. Source: Archives of Dermatology. 1980 April; 116(4): 438-40. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=6445177
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CHAPTER 2. NUTRITION AND TETRACYCLINE Overview In this chapter, we will show you how to find studies dedicated specifically to nutrition and tetracycline.
Finding Nutrition Studies on Tetracycline 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 “tetracycline” (or synonyms) into the search box, and click “Go.” To narrow the search, you can also select the “Title” field.
7
Adapted from http://ods.od.nih.gov. IBIDS is produced by the Office of Dietary Supplements (ODS) at the National Institutes of Health to assist the public, healthcare providers, educators, and researchers in locating credible, scientific information on dietary supplements. IBIDS was developed and will be maintained through an interagency partnership with the Food and Nutrition Information Center of the National Agricultural Library, U.S. Department of Agriculture.
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The following information is typical of that found when using the “Full IBIDS Database” to search for “tetracycline” (or a synonym): •
15-Ketodihydro-PGF(2 alpha), progesterone and uterine involution in primiparous cows with induced retained placenta and post-partal endometritis treated with oxytetracycline and flunixin. Author(s): Department of Obstetrics and Gynaecology, Centre for Reproductive Biology in Uppsala, Swedish University of Agricultural Sciences (SLU), Uppsala, Sweden.
[email protected] Source: Konigsson, K Gustafsson, H Kindahl, H Reprod-Domest-Anim. 2002 February; 37(1): 43-51 0936-6768
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Amoxicillin/tetracycline combinations are inadequate as alternative therapies for Helicobacter pylori infection. Author(s): Department of Internal Medicine, Gastroenterology Unit, Casa Sollievo della Sofferenza Hospital, I.R.C.C.S., San Giovanni Rotondo, Italy. Source: Perri, Francesco Festa, Virginia Merla, Antonio Quitadamo, Michele Clemente, Rocco Andriulli, Angelo Helicobacter. 2002 April; 7(2): 99-104 1083-4389
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Characterization of the tetracycline resistance plasmid pMD5057 from Lactobacillus plantarum 5057 reveals a composite structure. Author(s): Applied Biotechnology, Identification Section, Chr. Hansen A/S, Boge Alle 10-12, 2970 Horsholm, Denmark.
[email protected] Source: Danielsen, M Plasmid. 2002 September; 48(2): 98-103 0147-619X
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Compliance with artesunate and quinine + tetracycline treatment of uncomplicated falciparum malaria in Thailand. Author(s): Department of Social and Environmental Medicine, Faculty of Tropical Medicine, Mahidol University, Bangkok, Thailand. Source: Fungladda, W Honrado, E R Thimasarn, K Kitayaporn, D Karbwang, J Kamolratanakul, P Masngammueng, R Bull-World-Health-Organ. 1998; 76 Suppl 159-66 0042-9686
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Composition and antibiotic resistance profile of microcosm dental plaques before and after exposure to tetracycline. Author(s): Department of Microbiology, Eastman Dental Hospital, University College London Hospitals NHS Trust, UK.
[email protected] Source: Ready, D Roberts, A P Pratten, J Spratt, D A Wilson, M Mullany, P J-AntimicrobChemother. 2002 May; 49(5): 769-75 0305-7453
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Cost-effectiveness analysis of artesunate and quinine + tetracycline for the treatment of uncomplicated falciparum malaria in Chanthaburi, Thailand. Author(s): Research Institute for Tropical Medicine, Department of Health, Muntinlupa City, Metro Manila, Philippines. Source: Honrado, E R Fungladda, W Kamoiratanaku, P Kitayaporn, D Karbwang, J Thimasarn, K Masngammueng, R Bull-World-Health-Organ. 1999; 77(3): 235-43 00429686
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Dental and oral discolorations associated with minocycline and other tetracycline analogs. Author(s): University of North Carolina School of Dentistry, Chapel Hill, USA. Source: Cheek, C C Heymann, H O J-Esthet-Dent. 1999; 11(1): 43-8 1040-1466
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Design, characterisation and preliminary clinical evaluation of a novel mucoadhesive topical formulation containing tetracycline for the treatment of periodontal disease. Author(s): School of Pharmacy, The Queen's University of Belfast, Medical Biology Centre, 97, Lisburn Road, BT9 7BL, Northern Ireland, Belfast, UK.
[email protected]
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Source: Jones, D S Woolfson, A D Brown, A F Coulter, W A McClelland, C Irwin, C R JControl-Release. 2000 July 3; 67(2-3): 357-68 0168-3659 •
Effect of soybean oil on oxygen transfer in the production of tetracycline with an airlift bioreactor. Author(s): Tianjin Univ. of Light Industry (China) Source: Jia, S. Chen, G. Kahar, P. Choi, D.B. Okabe, M. Journal-of-Bioscience-andBioengineering (Japan). (June 1999). volume 87(6) page 825-827. streptomyces tetracyclines bioreactors soybean oil oxygen 1389-1723
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Effect of tetracycline treatment on the development of citrus blight symptoms. Source: Timmer, L.W. Graham, J.H. Lee, R.F. Proceedings-of-the-.-annual-meeting-ofthe-Florida-State-Horticulture-Society (USA). (1986). volume 98 page 3-6. citrus sinensis blights symptoms tetracyclines therapy 0886-7283
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Efficacy of minocycline as a root conditioner in comparison to citric acid and tetracycline. An in vitro evaluation. Author(s): Department of Periodontics, College of Dental Surgery, Manipal, India. Source: Thomas, B S Varma, B R Bhat, K M Indian-J-Dent-Res. 1999 Apr-June; 10(2): 6975 0970-9290
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Eradication of Helicobacter pylori in duodenal ulcer disease tetracycline & furazolidone vs. metronidazole & amoxicillin in omeprazole based triple therapy. Author(s): Gastrointestinal & liver Diseases Research center, Guilan University of Medical Sciences, Rasht, Iran.
[email protected] Source: Mansour Ghanaei, Fariborz Fallah, Mohammad S Shafaghi, Afshin Med-SciMonit. 2002 March; 8(3): PI27-30 1234-1010
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Functional determinants for the tetracycline-dependent transactivator tTA in transgenic mouse embryos. Author(s): Department of Molecular Cell Biology, Max-Planck-Institute for Biophysical Chemistry, Am Fassberg, 37077, Gottingen, Germany. Source: Bogeroger, H Gruss, P Mech-Devolume 1999 May; 83(1-2): 141-53 0925-4773
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Improving compliance with quinine + tetracycline for treatment of malaria: evaluation of health education interventions in Cambodian villages. Author(s): Ministry of Health National Malaria Centre, Phnom Penh, Cambodia. Source: Denis, M B Bull-World-Health-Organ. 1998; 76 Suppl 143-9 0042-9686
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In vitro synergy between ranitidine bismuth citrate and tetracycline or clarithromycin against resistant strains of Helicobacter pylori. Author(s): Microbiology Department, Southern Health Care Network, Monash Medical Centre, Clayton, Australia.
[email protected] Source: Midolo, P D Lambert, J R Kerr, T G Tee, W Eur-J-Clin-Microbiol-Infect-Dis. 1999 November; 18(11): 832-4 0934-9723
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Influence of liquids (coffee and orange juice) on the bioavailability of tetracycline. Author(s): Departamento de Farmacia y Bioquimica, Facultad de Quimica, Universidad Nacional Autonoma de Mexico. Source: Jung, H Rivera, O Reguero, M T Rodriguez, J M Moreno Esparza, R BiopharmDrug-Dispos. 1990 November; 11(8): 729-34 0142-2782
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Inhibitory effects of some medicinal plants on germ cell genotoxicity of methylmethanesulfonate, tetracycline and chloromycetine. Author(s): Philippines Univ., Diliman, Quezon City (Philippines). Inst. of Chemistry Source: Sylianco, C.Y.L. Abian, R. Wu, L.S. Philippine-Journal-of-Science (Philippines). (Apr-June 1991). volume 120(2) page 191-201. Issued Jun 1992. 0031-7683
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Investigation of a tetracycline-regulated phage display system. Author(s): Institut fur Biochemie (Charite), Humboldt-Universitat zu Berlin, Monbijoustr.2, D-10117 Berlin, Germany. Source: Zahn, G Skerra, A Hohne, W Protein-Eng. 1999 December; 12(12): 1031-4 02692139
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In-vitro release characteristics of tetracycline HCl, khellin and nicotinamide adenine dineculeotide from halloysite; a cylindrical mineral. Author(s): Laboratory for Molecular Interfacial Interactions, Code 6930, Naval Research Laboratory, Washington, DC 20375, USA.
[email protected] Source: Price, R R Gaber, B P Lvov, Y J-Microencapsul. 2001 Nov-December; 18(6): 71322 0265-2048
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Oestradiol combined with oxytetracycline as therapy for severe bovine anaplasmosis. Author(s): University of Idaho, Caine Veterinary Teaching and Research Center, Caldwell, Idaho 83605, USA. Source: Zaugg, J L Vet-Rec. 1998 January 10; 142(2): 44 0042-4900
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Omeprazole, furazolidone, and tetracycline: an eradication treatment for resistant H. pylori in Brazilian patients with peptic ulcer disease. Author(s): Hospital das Clinicas, Faculty of Medicine, University of Sao Paulo, Brazil. Source: Silva, F M Eisig, J N Chehter, E Z Silva, J J Laudanna, A A Rev-Hosp-Clin-FacMed-Sao-Paulo. 2002 Sep-October; 57(5): 205-8 0041-8781
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Patient selection and clinical applications of periodontal tetracycline fibers. Author(s): Section of Pediatric Dentistry, University of California-Los Angeles School of Dentistry, USA. Source: Latner, L Gen-Dent. 1998 Jan-February; 46(1): 58-61 0363-6771
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Release kinetics of 25% tetracycline hydrochloride-loaded ethylene vinyl acetate fibers. Author(s): Department of Periodontology, University of Istanbul, Faculty of Dentistry, Turkey.
[email protected] Source: Demirel, K Yalcin, F Polat, E Onan, U Meric, H Altas, K Periodontal-ClinInvestig. 1999; 21(1): 6-9 1065-2418
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Root-surface caries in rats and humans: inhibition by a non-antimicrobial property of tetracyclines. Author(s): Department of Oral Biology and Pathology, School of Dental Medicine, SUNY at Stony Brook 11794-8702, USA. Source: Ramamurthy, N S Schroeder, K L McNamara, T F Gwinnett, A J Evans, R T Bosko, C Golub, L M Adv-Dent-Res. 1998 November; 12(2): 43-50 0895-9374
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Tetracycline absorption in malnutrition. Source: Raghuram, Thummala C. Krishnaswamy, Kamala. Drug-Nutrient-Interact. New York : Alan R. Liss, Inc. 1981. volume 1 (1) page 23-29. charts. 0272-3530
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Tetracycline and niacinamide in the treatment of blistering skin diseases. Author(s): Hospital For Skin and Venereal Diseases, Department of Dermatology and Venereology, Thessaloniki, Greece.
[email protected] Source: Chaidemenos, G C Clin-Dermatol. 2001 Nov-December; 19(6): 781-5 0738-081X
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Tetracycline HCl solution as a root canal irrigant. Author(s): Department of Endodontics, Faculty of Dentistry, Istanbul University, Turkey. Source: Haznedaroglu, F Ersev, H J-Endod. 2001 December; 27(12): 738-40 0099-2399
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Tetracyclines inhibit nitrosothiol production by cytokine-stimulated osteoarthritic synovial cells. Author(s): Laboratoire de Biochimie A, Hjpital Cochin, Paris, France.
[email protected] Source: Borderie, D Hernvann, A Hilliquin, P Lemarchal, H Kahan, A Ekindjian, O G Inflamm-Res. 2001 August; 50(8): 409-14 1023-3830
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The effects of chemically modified tetracyclines (CMTs) on human keratinocyte proliferation and migration. Author(s): Department of Periodontology, Institute of Dentistry, University of Turku, Finland. Source: Makela, M Sorsa, T Uitto, V J Salo, T Teronen, O Larjava, H Adv-Dent-Res. 1998 November; 12(2): 131-5 0895-9374
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The effects of pH and PEG 400-water cosolvents on oxytetracycline-magnesium complex formation and stability. Author(s): Whitehall-Robins Healthcare, Richmond, Virginia 23220, USA.
[email protected] Source: Tongaree, S Goldberg, A M Flanagan, D R Poust, R I Pharm-Dev-Technol. 2000; 5(2): 189-99 1083-7450
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Tightly regulated and inducible expression of rabbit CYP2E1 using a tetracyclinecontrolled expression system. Author(s): Department of Physiology and Pharmacology, Oregon Health Sciences University, Portland, Oregon 97201, USA. Source: Huan, J Y Koop, D R Drug-Metab-Dispos. 1999 April; 27(4): 549-54 0090-9556
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Transfer of chlortetracycline from contaminated feedingstuff to cows' milk. Author(s): Department of Agriculture for Northern Ireland, Stormont, Belfast. Source: McEvoy, J D Mayne, C S Higgins, H C Kennedy, D G Vet-Rec. 2000 January 22; 146(4): 102-6 0042-4900
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Treatment of peri-implantitis by local delivery of tetracycline. Clinical, microbiological and radiological results. Author(s): School of Dental Medicine, University of Geneva, 19 rue Barthelemy-Menn, CH-1211 Geneva 4, Switzerland.
[email protected] Source: Mombelli, A Feloutzis, A Bragger, U Lang, N P Clin-Oral-Implants-Res. 2001 August; 12(4): 287-94 0905-7161
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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WebMDHealth: 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 tetracycline; 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 Ascorbic Acid Alternative names: Vitamin C (Ascorbic Acid) Source: Integrative Medicine Communications; www.drkoop.com Folic Acid Source: Healthnotes, Inc.; www.healthnotes.com Folic Acid Alternative names: Vitamin B9 (Folic Acid) Source: Integrative Medicine Communications; www.drkoop.com
Nutrition
Niacin Alternative names: Vitamin B3 (Niacin) Source: Integrative Medicine Communications; www.drkoop.com Pyridoxine Alternative names: Vitamin B6 (Pyridoxine) Source: Integrative Medicine Communications; www.drkoop.com Riboflavin Alternative names: Vitamin B2 (Riboflavin) Source: Integrative Medicine Communications; www.drkoop.com Thiamine Alternative names: Vitamin B1 (Thiamine) Source: Integrative Medicine Communications; www.drkoop.com Vitamin B1 (Thiamine) Alternative names: Thiamine Source: Integrative Medicine Communications; www.drkoop.com Vitamin B12 Source: Healthnotes, Inc.; www.healthnotes.com Vitamin B12 (Cobalamin) Alternative names: Cobalamin Source: Integrative Medicine Communications; www.drkoop.com Vitamin B2 Source: Healthnotes, Inc.; www.healthnotes.com Vitamin B2 (Riboflavin) Alternative names: Riboflavin Source: Integrative Medicine Communications; www.drkoop.com Vitamin B3 Source: Healthnotes, Inc.; www.healthnotes.com Vitamin B3 (Niacin) Alternative names: Niacin Source: Integrative Medicine Communications; www.drkoop.com Vitamin B6 Source: Healthnotes, Inc.; www.healthnotes.com Vitamin B6 (Pyridoxine) Alternative names: Pyridoxine Source: Integrative Medicine Communications; www.drkoop.com Vitamin B9 (Folic Acid) Alternative names: Folate Source: Integrative Medicine Communications; www.drkoop.com
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Vitamin C Source: Healthnotes, Inc.; www.healthnotes.com Vitamin C (Ascorbic Acid) Alternative names: Ascorbic Acid Source: Integrative Medicine Communications; www.drkoop.com Vitamin K Source: Healthnotes, Inc.; www.healthnotes.com •
Minerals Calcium Source: Healthnotes, Inc.; www.healthnotes.com Calcium Source: Integrative Medicine Communications; www.drkoop.com Calcium Source: WholeHealthMD.com, LLC.; www.wholehealthmd.com Hyperlink: http://www.wholehealthmd.com/refshelf/substances_view/0,1525,884,00.html Folate Alternative names: Vitamin B9 (Folic Acid) Source: Integrative Medicine Communications; www.drkoop.com Iron Source: Healthnotes, Inc.; www.healthnotes.com Iron Alternative names: Ferrous Sulfate Source: Integrative Medicine Communications; www.drkoop.com Magnesium Source: Healthnotes, Inc.; www.healthnotes.com Magnesium Source: Integrative Medicine Communications; www.drkoop.com Magnesium Source: Prima Communications, Inc.www.personalhealthzone.com Magnesium Source: WholeHealthMD.com, LLC.; www.wholehealthmd.com Hyperlink: http://www.wholehealthmd.com/refshelf/substances_view/0,1525,890,00.html Potassium Source: Healthnotes, Inc.; www.healthnotes.com
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Zinc Source: Healthnotes, Inc.; www.healthnotes.com Zinc Source: Integrative Medicine Communications; www.drkoop.com Zinc Source: Prima Communications, Inc.www.personalhealthzone.com Zinc Source: WholeHealthMD.com, LLC.; www.wholehealthmd.com Hyperlink: http://www.wholehealthmd.com/refshelf/substances_view/0,1525,10071,00.html •
Food and Diet Ferrous Sulfate Alternative names: Iron Source: Integrative Medicine Communications; www.drkoop.com
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CHAPTER 3. ALTERNATIVE MEDICINE AND TETRACYCLINE Overview In this chapter, we will begin by introducing you to official information sources on complementary and alternative medicine (CAM) relating to tetracycline. 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 tetracycline 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 “tetracycline” (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 tetracycline: •
A comparative study of raw garlic extract and tetracycline on caecal microflora and serum proteins of albino rats. Author(s): Shashikanth KN, Basappa SC, Sreenivasa Murthy V. Source: Folia Microbiol (Praha). 1984; 29(4): 348-52. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=6479758
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A high performance liquid chromatographic system for the analysis of tetracycline drug standards, analogs, degradation products and other impurities. Author(s): Mack GD, Ashworth RB. Source: Journal of Chromatographic Science. 1978 March 10; 16(3): 93-101. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=641134
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A novel positive tetracycline-dependent transactivator (rtTA) variant with reduced background activity and enhanced activation potential. Author(s): Kamper MR, Gohla G, Schluter G.
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Source: Febs Letters. 2002 April 24; 517(1-3): 115-20. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12062420 •
Absorption and excretion of drugs. XXXVII. Effect of Ca2+ on the absorption of tetracycline from the small intestine. (2). Author(s): Kakemi K, Sezaki H, Hayashi M, Nadai T. Source: Chemical & Pharmaceutical Bulletin. 1968 November; 16(11): 2206-12. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=4975993
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Active accumulation of tetracycline by Escherichia coli. Author(s): Franklin TJ, Higginson B. Source: The Biochemical Journal. 1970 January; 116(2): 287-97. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=4984165
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Amoxicillin/tetracycline combinations are inadequate as alternative therapies for Helicobacter pylori infection. Author(s): Perri F, Festa V, Merla A, Quitadamo M, Clemente R, Andriulli A. Source: Helicobacter. 2002 April; 7(2): 99-104. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11966868
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An original approach to determining traces of tetracycline antibiotics in milk and eggs by solid-phase extraction and liquid chromatography/mass spectrometry. Author(s): Bruno F, Curini R, Corcia AD, Nazzari M, Pallagrosi M. Source: Rapid Communications in Mass Spectrometry : Rcm. 2002; 16(14): 1365-76. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12112617
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Antibacterial action of combinations of oxytetracycline, dimethyl sulfoxide, and EDTA-tromethamine on Proteus, Salmonella, and Aeromonas. Author(s): Wooley RE, Gilbert JP, Shotts EB Jr. Source: Am J Vet Res. 1982 January; 43(1): 130-3. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=6807142
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Anti-ulcer effects of antioxidants, quercetin, alpha-tocopherol, nifedipine and tetracycline in rats. Author(s): Suzuki Y, Ishihara M, Segami T, Ito M. Source: Japanese Journal of Pharmacology. 1998 December; 78(4): 435-41. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=9920200
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Assay and purity control of tetracycline, chlortetracycline and oxytetracycline in animal feeds and premixes by TLC densitometry with fluorescence detection. Author(s): Naidong W, Hua S, Roets E, Hoogmartens J.
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Source: Journal of Pharmaceutical and Biomedical Analysis. 2003 September 15; 33(1): 85-93. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12946534 •
Assay of chlortetracycline in animal feeds by liquid chromatography with fluorescence detection. Author(s): Houglum JE, Larson RD, Knutson A. Source: J Aoac Int. 1997 September-October; 80(5): 961-5. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=9325574
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Attempted reversal of oxytetracycline resistance of Proteus mirabilis by EDTAtromethamine lavage in experimentally induced canine and feline cystitis. Author(s): Wooley RE, Blue JL, Campbell LM. Source: Am J Vet Res. 1975 October; 36(10): 1533-5. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=811139
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Binding study of tetracyclines to human serum albumin using difference spectrophotometry. Author(s): Zia H, Price JC. Source: Journal of Pharmaceutical Sciences. 1976 February; 65(2): 226-30. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=3641
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Bisphosphonates and tetracycline: experimental models for their evaluation in calcium-related disorders. Author(s): Cohen H, Solomon V, Alferiev IS, Breuer E, Ornoy A, Patlas N, Eidelman N, Hagele G, Golomb G. Source: Pharmaceutical Research. 1998 April; 15(4): 606-13. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=9587958
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Ca2+ mobilization in blood platelets as visualized by chlortetracycline fluorescence. Author(s): Owen NE, Le Breton GC. Source: The American Journal of Physiology. 1981 October; 241(4): H613-9. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=6274207
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Characterization of the active transport of chlorotetracycline in staphylococcus aureus by a fluorescence technique. Author(s): Dockter ME, Magnuson JA. Source: J Supramol Struct. 1974; 2(1): 32-44. No Abstract Available. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=4211866
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Chlortetracycline and the transmembrane potential of the inner membrane of plant mitochondria. Author(s): Moller IM, Kay CJ, Palmer JM.
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Source: The Biochemical Journal. 1986 August 1; 237(3): 765-71. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=3800917 •
Comparative SEM study on the effect of root conditioning with EDTA or tetracycline Hcl on periodontally involved root surfaces. Author(s): Babay N. Source: Indian J Dent Res. 2000 April-June; 11(2): 53-7. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11307429
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Compensation of dietary induced reduction of tetracycline absorption by simultaneous administration of EDTA. Author(s): Poiger H, Schlatter C. Source: European Journal of Clinical Pharmacology. 1978 November 16; 14(2): 129-31. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=102512
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Conditional transformation of a pancreatic beta-cell line derived from transgenic mice expressing a tetracycline-regulated oncogene. Author(s): Efrat S, Fusco-DeMane D, Lemberg H, al Emran O, Wang X. Source: Proceedings of the National Academy of Sciences of the United States of America. 1995 April 11; 92(8): 3576-80. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=7724601
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Dental and oral discolorations associated with minocycline and other tetracycline analogs. Author(s): Cheek CC, Heymann HO. Source: J Esthet Dent. 1999; 11(1): 43-8. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=10337289
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Determination of meclocycline, a tetracycline analogue, in cream formulations by liquid chromatography. Author(s): Depaolis AM, Britt TE, Holman AJ, McGonigle EJ, Kaplan G, Davies WC. Source: Journal of Pharmaceutical Sciences. 1984 November; 73(11): 1650-1. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=6520775
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Determination of oxytetracycline and its decomposition products in Tetran vulnerary powder. Author(s): Morovjan GY, Horvath E, Vagi I, Fekete J. Source: Acta Pharm Hung. 1994 March; 64(2): 67-73. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=8017211
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Determination of oxytetracycline residues in matrixes from a freshwater recirculating aquaculture system. Author(s): Carson MC, Bullock G, Bebak-Williams J.
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Source: J Aoac Int. 2002 March-April; 85(2): 341-8. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11990017 •
Determination of tetracycline antibiotics by reversed-phase high-performance liquid chromatography with fluorescence detection. Author(s): Iwaki K, Okumura N, Yamazaki M. Source: Journal of Chromatography. 1992 October 9; 623(1): 153-8. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=1452626
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Determination of tetracycline antibiotics in animal tissues of food-producing animals by high-performance liquid chromatography using solid-phase extraction. Author(s): Sokol J, Matisova E. Source: J Chromatogr A. 1994 May 27; 669(1-2): 75-80. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=8055105
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Determination of tetracycline antibiotics in salmon muscle by liquid chromatography using post-column derivatization with fluorescence detection. Author(s): Pena AL, Lino CM, Silveira MI. Source: J Aoac Int. 2003 September-October; 86(5): 925-9. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=14632392
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Determination of tetracyclines in bovine and porcine muscle by high-performance liquid chromatography using solid-phase extraction. Author(s): Walsh JR, Walker LV, Webber JJ. Source: Journal of Chromatography. 1992 April 10; 596(2): 211-6. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=1400838
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Development and validation of a sensitive method for tetracycline in gingival crevicular fluid by HPLC using fluorescence detection. Author(s): Vienneau DS, Kindberg CG. Source: Journal of Pharmaceutical and Biomedical Analysis. 1997 September; 16(1): 1117. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=9447558
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Drug-induced histological changes and its consequences on the permeability of the small intestinal mucosa. I. EDTA, tetracycline, and sodium laurylsulfate. Author(s): Nadai T, Kondo R, Tatematsu A, Sezaki H. Source: Chemical & Pharmaceutical Bulletin. 1972 June; 20(6): 1139-44. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=4627198
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Effect of certain additives on photodegradation of tetracycline hydrochloride solutions. Author(s): Asker AF, Habib MJ.
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Source: J Parenter Sci Technol. 1991 March-April; 45(2): 113-5. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=2051256 •
Effect of osmotic shock on tetracycline resistance in Escherichia coli bearing an Rfactor. Author(s): Franklin TJ, Foster SJ. Source: The Biochemical Journal. 1971 January; 121(2): 287-92. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=5000645
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Effects of demineralizing tetracycline-stained human dentine. Author(s): Simpson MS. Source: Calcified Tissue International. 1981; 33(2): 101-4. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=6163512
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Enhancement of low density lipoprotein binding to both low density lipoprotein receptor-positive and -negative cells by tetracycline antibiotics. Author(s): Miura S, Hasumi K, Takayasu R, Sugimoto M, Endo A. Source: Lipids. 1998 January; 33(1): 33-8. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=9470171
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Ethylenediaminetetraacetic acid tetracycline and toxicity of barium chloride and sodium fluoride. Author(s): Gogte ST. Source: Indian J Physiol Pharmacol. 1970 January; 14(1): 61-2. No Abstract Available. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=5500721
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Fluorometric determination of tetracyclines in small blood and tissue samples. Author(s): van den Bogert C, Kroon AM. Source: Journal of Pharmaceutical Sciences. 1981 February; 70(2): 186-9. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=6782190
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Fluorometric study of tetracycline--bovine serum albumin interaction. The tetracyclines--a new class of fluorescent probes. Author(s): Popov PG, Vaptzarova KI, Kossekova GP, Nikolov TK. Source: Biochemical Pharmacology. 1972 September 1; 21(17): 2363-72. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=4630490
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Gamma globulin, Evan's blue, aprotinin A PLA2 inhibitor, tetracycline and antioxidants protect epithelial cells against damage induced by synergism among streptococcal hemolysins, oxidants and proteinases: relation to the prevention of poststreptococcal sequelae and septic shock. Author(s): Ginsburg I, Sadovnic M.
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Source: Fems Immunology and Medical Microbiology. 1998 November; 22(3): 247-56. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=9848686 •
Growth performance and immune response of two commercial broiler strains fed diets containing Lactobacillus cultures and oxytetracycline under heat stress conditions. Author(s): Zulkifli I, Abdulllah N, Azrin NM, Ho YW. Source: British Poultry Science. 2000 December; 41(5): 593-7. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11201439
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High-performance liquid chromatographic determination of oxytetracycline in channel catfish (Ictalurus punctatus) muscle tissue. Author(s): Moretti VM, Maggi GL, Albertini A, Bellagamba F, Luzzana U, Serrini G, Valfre F. Source: The Analyst. 1994 December; 119(12): 2749-51. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=7879888
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High-performance liquid chromatographic procedures for the quantitative analysis of 15 tetracycline derivatives in small blood samples. Author(s): Kramer-Horaczynska F. Source: Journal of Chromatographic Science. 1991 March; 29(3): 107-13. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=1905732
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Histamine release by compound 48/80: evidence for the depletion and repletion of calcium using chlortetracycline and 45calcium. Author(s): WoldeMussie E, Moran NC. Source: Agents Actions. 1984 October; 15(3-4): 267-72. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=6084410
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Improvement of chemical analysis of antibiotics. IX. A simple method for residual tetracyclines analysis in honey using a tandem cartridge clean-up system. Author(s): Oka H, Ikai Y, Kawamura N, Uno K, Yamada M, Harada K, Uchiyama M, Asukabe H, Mori Y, Suzuki M. Source: Journal of Chromatography. 1987 March 13; 389(2): 417-26. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=3106387
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In vitro histological and tetracycline staining properties of surface layer rat incisor enamel also reflect the cyclical nature of the maturation process. Author(s): Boyde A, Reith EJ. Source: Histochemistry. 1982; 75(3): 341-51. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=6183240
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In vitro studies on colonization resistance of the human gut microbiota to Candida albicans and the effects of tetracycline and Lactobacillus plantarum LPK. Author(s): Payne S, Gibson G, Wynne A, Hudspith B, Brostoff J, Tuohy K. Source: Curr Issues Intest Microbiol. 2003 March; 4(1): 1-8. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12691257
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Influence of tetracyclines and light on the release of lysozyme from human granulocytes and monocytes. Author(s): Glette J, Haneberg B, Sornes S, Sandberg S, Solberg CO. Source: International Journal of Immunopharmacology. 1986; 8(8): 875-80. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=3804532
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Inhibition of polymorphonuclear leukocyte functions by chlortetracycline. Author(s): Elferink JG, Deierkauf M. Source: Biochemical Pharmacology. 1984 November 15; 33(22): 3667-73. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=6439210
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Inhibitory effect of various iron salts on the absorption of tetracycline in man. Author(s): Neuvonen PJ, Turakka H. Source: European Journal of Clinical Pharmacology. 1974 August 23; 7(5): 357-60. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=4213690
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Inhibitory effects of combinations of oxytetracycline, dimethyl sulfoxide, and EDTAtromethamine on Escherichia coli. Author(s): Wooley RE, Gilbert JP, Shotts EB Jr. Source: Am J Vet Res. 1981 November; 42(11): 2010-3. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=6802044
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Interaction of cations and chelators with the intestinal absorption of tetracycline. Author(s): Poiger H, Schlatter C. Source: Naunyn-Schmiedeberg's Archives of Pharmacology. 1979 January 31; 306(1): 8992. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=106309
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Intracellular divalent cation release in pancreatic acinar cells during stimulussecretion coupling. II. Subcellular localization of the fluorescent probe chlorotetracycline. Author(s): Chandler DE, Williams JA. Source: The Journal of Cell Biology. 1978 February; 76(2): 386-99. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=10605445
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Ion chromatographic analysis of tetracyclines using polymeric column and acidic eluent. Author(s): Ding X, Mou S. Source: J Chromatogr A. 2000 November 3; 897(1-2): 205-14. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11128204
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Kinetics of chlorotetracycline permeation in fragmented, ATPase-rich sarcoplasmic reticulum. Author(s): Millman MS, Caswell AH, Haynes DH. Source: Membr Biochem. 1980; 3(4): 291-315. No Abstract Available. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=6783811
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Liquid chromatographic and flow injection analysis of tetracycline using sensitized europium (III) luminescence detection. Author(s): Wenzel TJ, Collette LM, Dahlen DT, Hendrickson SM, Yarmaloff LW. Source: Journal of Chromatography. 1988 December 9; 433: 149-58. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=3235543
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Liquid chromatographic determination of oxytetracycline in swine tissues. Author(s): Kawata S, Sato K, Nishikawa Y, Iwama K. Source: J Aoac Int. 1996 November-December; 79(6): 1463-5. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=8946724
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Liquid chromatography with ultraviolet absorbance detection for the analysis of tetracycline residues in honey. Author(s): Vinas P, Balsalobre N, Lopez-Erroz C, Hernandez-Cordoba M. Source: J Chromatogr A. 2004 January 2; 1022(1-2): 125-9. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=14753778
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Matrix solid-phase dispersion (MSPD) isolation and liquid chromatographic determination of oxytetracycline, tetracycline, and chlortetracycline in milk. Author(s): Long AR, Hsieh LC, Malbrough MS, Short CR, Barker SA. Source: J Assoc Off Anal Chem. 1990 May-June; 73(3): 379-84. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=2115861
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Nodulocystic acne: oral gugulipid versus tetracycline. Author(s): Thappa DM, Dogra J. Source: The Journal of Dermatology. 1994 October; 21(10): 729-31. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=7798429
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On-line metal chelate affinity chromatography clean-up for the high-performance liquid chromatographic determination of tetracycline antibiotics in animal tissues. Author(s): Stubbings G, Tarbin JA, Shearer G.
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Source: Journal of Chromatography. B, Biomedical Applications. 1996 April 26; 679(1-2): 137-45. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=8998553 •
Oxidation photosensitized by tetracyclines. Author(s): Wiebe JA, Moore DE. Source: Journal of Pharmaceutical Sciences. 1977 February; 66(2): 186-9. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=14244
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Oxytetracycline production by immobilized Streptomyces rimosus. Author(s): Yang SS, Yueh CY. Source: J Microbiol Immunol Infect. 2001 December; 34(4): 235-42. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11825002
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Paper chromatographic determination of tetracycline. Author(s): Youssef MK, Ibrahim EA, Attia IA. Source: Journal of Pharmaceutical Sciences. 1973 December; 62(12): 1998-2001. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=4202679
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Potent inhibitors of human immunodeficiency virus type 1 integrase: identification of a novel four-point pharmacophore and tetracyclines as novel inhibitors. Author(s): Neamati N, Hong H, Sunder S, Milne GW, Pommier Y. Source: Molecular Pharmacology. 1997 December; 52(6): 1041-55. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=9415714
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Production of oxytetracycline by Streptomyces rimosus 12,907 as an animal feed supplement. Author(s): Baghlaf AO, Abou-Zeid AZ, El-Dewany AI, Eissa A el-W, Fouad M, Yassein M. Source: Zentralbl Bakteriol Naturwiss. 1980; 135(5): 427-34. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=7192913
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Promotion of bone calcification by sodium fluoride. Short-term experiments on newborn rats using tetracycline labeling. Author(s): Petrovic A, Shambaugh GE Jr. Source: Arch Otolaryngol. 1966 February; 83(2): 162-70. No Abstract Available. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=4955161
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Protective effect of picroliv, active constituent of Picrorhiza kurrooa, against oxytetracycline induced hepatic damage. Author(s): Saraswat B, Visen PK, Patnaik GK, Dhawan BN.
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Source: Indian J Exp Biol. 1997 December; 35(12): 1302-5. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=9567764 •
Quantitation of antibiotics using high-pressure liquid chromatography: tetracycline. Author(s): Nilsson-Ehle I, Yoshikawa TT, Schotz MC, Guze LB. Source: Antimicrobial Agents and Chemotherapy. 1976 May; 9(5): 754-60. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=821388
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Quantitative determination by thin-layer chromatography of anhydrotetracyclines in degraded tetracycline tablets. Author(s): Simmons DL, Woo HS, Koorengevel CM, Seers P. Source: Journal of Pharmaceutical Sciences. 1966 November; 55(11): 1313-5. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=4961421
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Quantitative studies on the accumulation of tetracycline in tumors. Author(s): Winkelman J, Gorstein F. Source: Experientia. 1971 March 15; 27(3): 309-10. No Abstract Available. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=4993735
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Rapid and simple determination of oxytetracycline in chicken products. Author(s): Furusawa N. Source: J Aoac Int. 1999 May-June; 82(3): 770-2. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=10367394
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Rapid separation of tetracycline derivatives and their main degradation products by capillary zone electrophoresis. Author(s): Garcia-Ruiz C, Crego AL, Lavandera JL, Marina ML. Source: Electrophoresis. 2001 August; 22(13): 2775-81. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11545407
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Resistance to tetracycline, a hydrophilic antibiotic, is mediated by P-glycoprotein in human multidrug-resistant cells. Author(s): Kavallaris M, Madafiglio J, Norris MD, Haber M. Source: Biochemical and Biophysical Research Communications. 1993 January 15; 190(1): 79-85. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=8093660
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Reversed-phase ion-pair chromatographic analysis of tetracycline antibiotics. Application to discolored teeth. Author(s): Tanase S, Tsuchiya H, Yao J, Ohmoto S, Takagi N, Yoshida S.
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Source: J Chromatogr B Biomed Sci Appl. 1998 March 20; 706(2): 279-85. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=9551814 •
Role of oxygen radicals in the phototoxicity of tetracyclines toward Escherichia coli B. Author(s): Martin JP Jr, Colina K, Logsdon N. Source: Journal of Bacteriology. 1987 June; 169(6): 2516-22. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=3034858
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Sensitive detection of tetracyclines using europium-sensitized fluorescence with EDTA as co-ligand and cetyltrimethylammonium chloride as surfactant. Author(s): Arnaud N, Georges J. Source: The Analyst. 2001 May; 126(5): 694-7. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11394316
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Simultaneous determination of multiple tetracycline residues in milk by metal chelate affinity chromatography: collaborative study. Author(s): Carson MC, Breslyn W. Source: J Aoac Int. 1996 January-February; 79(1): 29-42. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=8620108
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Simultaneous determination of multiple tetracycline residues in milk using metal chelate affinity chromatography. Author(s): Carson MC. Source: J Aoac Int. 1993 March-April; 76(2): 329-34. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=8471858
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Simultaneous determination of oxytetracycline, tetracycline, and chlortetracycline in milk by liquid chromatography. Author(s): Thomas MH. Source: J Assoc Off Anal Chem. 1989 July-August; 72(4): 564-7. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=2759986
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Suppression of human neutrophil functions by tetracyclines. Author(s): Gabler WL, Creamer HR. Source: Journal of Periodontal Research. 1991 January; 26(1): 52-8. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=1847418
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Susceptible Escherichia coli cells can actively excrete tetracyclines. Author(s): McMurry LM, Aronson DA, Levy SB. Source: Antimicrobial Agents and Chemotherapy. 1983 October; 24(4): 544-51. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=6418064
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Tetracycline accumulation in toxic liver damage. Author(s): TAPP E, CARROLL R. Source: J Pathol Bacteriol. 1965 April; 89: 715-21. No Abstract Available. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=14320315
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Tetracycline and niacinamide for the treatment of sterile pyogranuloma/granuloma syndrome in a dog. Author(s): Rothstein E, Scott DW, Riis RC. Source: Journal of the American Animal Hospital Association. 1997 NovemberDecember; 33(6): 540-3. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=9358425
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Tetracycline inhibition of a lipase from Corynebacterium acnes. Author(s): Weaber K, Freedman R, Eudy WW. Source: Appl Microbiol. 1971 April; 21(4): 639-42. No Abstract Available. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=4252558
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Tetracycline transport in Bacteroides fragilis. Author(s): Fayolle F, Privitera G, Sebald M. Source: Antimicrobial Agents and Chemotherapy. 1980 October; 18(4): 502-5. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=7447414
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Tetracycline-chelated Mg2+ ion initiates helix unwinding in Tet repressor induction. Author(s): Orth P, Saenger W, Hinrichs W. Source: Biochemistry. 1999 January 5; 38(1): 191-8. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=9890898
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Tetracyclines I. Separation and examination by thin-layer chromatography. Author(s): Ascione PP, Zagar JB, Chrekian GP. Source: Journal of Pharmaceutical Sciences. 1967 November; 56(11): 1393-404. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=4964773
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Tetracyclines inhibit human synovial collagenase in vivo and in vitro. Author(s): Greenwald RA, Golub LM, Lavietes B, Ramamurthy NS, Gruber B, Laskin RS, McNamara TF. Source: The Journal of Rheumatology. 1987 February; 14(1): 28-32. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=3033237
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The antagonistic action of metallic cations to the enhancing activity of phoscolic acid, a tetracycline adjuvant. Author(s): Takesue EI, Peets LM, Wilcox RA.
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Source: Arch Int Pharmacodyn Ther. 1965 May; 155(1): 21-9. No Abstract Available. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=5834937 •
The effect of ethylenediaminetetraacetic acid (EDTA) and ascorbic acid on tetracycline blood serum concentrations. Author(s): EISENBERG GM, WEISS W, FLIPPIN HF. Source: The Journal of Laboratory and Clinical Medicine. 1958 December; 52(6): 895-8. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=13611388
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The effect of reserpine, a modulator of multidrug efflux pumps, on the in vitro activity of tetracycline against clinical isolates of methicillin resistant Staphylococcus aureus (MRSA) possessing the tet(K) determinant. Author(s): Gibbons S, Udo EE. Source: Phytotherapy Research : Ptr. 2000 March; 14(2): 139-40. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=10685116
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The effect of tetracyclines on the rabbit heart. Author(s): Gyrd-Hansen N. Source: Zentralbl Veterinarmed A. 1980 May; 27(3): 228-37. No Abstract Available. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=6775464
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The effects of the periodical use of in-feed chlortetracycline on the reproductive performance of gilts and sows of a commercial pig farm with a history of clinical and subclinical viral and bacterial infections. Author(s): Alexopoulos C, Fthenakis GC, Burriel A, Bourtzi-Hatzopoulou E, Kritas SK, Sbiraki A, Kyriakis SC. Source: Reproduction in Domestic Animals = Zuchthygiene. 2003 June; 38(3): 187-92. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12753551
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The endoplasmic reticulum in the cortex of developing guard cells: coordinate studies with chlorotetracycline and osmium ferricyanide. Author(s): Palevitz BA, Hodge LD. Source: Developmental Biology. 1984 January; 101(1): 147-59. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=6198223
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The influence of EDTA on blood antibiotic levels following oral administration of tetracycline compounds. Author(s): Greene DE, Rinehart KE, Stephenson EL. Source: Poultry Science. 1968 September; 47(5): 1500-4. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=4973405
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The interaction between tetracycline and reconstituted guinea-pig-skin collagen in vitro. Author(s): JACOBS R, HARRIS WH, KATZ EP, GLIMCHER MJ. Source: Biochimica Et Biophysica Acta. 1964 June 8; 86: 579-87. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=14192909
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The transport of tetracyclines across the mouse ileum in vitro: the effect of cations and other agents. Author(s): Banerjee S, Chakrabarti K. Source: The Journal of Pharmacy and Pharmacology. 1976 February; 28(2): 133-8. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=6672
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TRH mobilizes membrane calcium in chlortetracycline. Author(s): Gershengorn MC, Thaw C. Source: The American Journal of Physiology.
thyrotropic
cells
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monitored
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Additional Web Resources A number of additional Web sites offer encyclopedic information covering CAM and related topics. The following is a representative sample: •
Alternative Medicine Foundation, Inc.: http://www.herbmed.org/
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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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WebMDHealth: 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/
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The following is a specific Web list relating to tetracycline; 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 Acne Source: Integrative Medicine Communications; www.drkoop.com Acne Source: Prima Communications, Inc.www.personalhealthzone.com Acne Vulgaris Source: Healthnotes, Inc.; www.healthnotes.com Bronchitis Source: Healthnotes, Inc.; www.healthnotes.com Canker Sores Source: Healthnotes, Inc.; www.healthnotes.com Cutaneous Drug Reactions Source: Integrative Medicine Communications; www.drkoop.com Dermatitis Herpetiformis Source: Healthnotes, Inc.; www.healthnotes.com Gastritis Source: Integrative Medicine Communications; www.drkoop.com Pancreatitis Source: Integrative Medicine Communications; www.drkoop.com Peptic Ulcer Source: Healthnotes, Inc.; www.healthnotes.com Peptic Ulcer Source: Integrative Medicine Communications; www.drkoop.com Photodermatitis Source: Integrative Medicine Communications; www.drkoop.com Photosensitivity Source: Healthnotes, Inc.; www.healthnotes.com Stomach Inflammation Source: Integrative Medicine Communications; www.drkoop.com Sunburn Source: Integrative Medicine Communications; www.drkoop.com
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Herbs and Supplements Amoxicillin Source: Healthnotes, Inc.; www.healthnotes.com Ananas Comosus Alternative names: Bromelain Source: Integrative Medicine Communications; www.drkoop.com Andrographis Alternative names: Andrographis paniculata Source: Healthnotes, Inc.; www.healthnotes.com Antibiotics Source: Healthnotes, Inc.; www.healthnotes.com Astragalus Mem Alternative names: Huang-Qi; Astragalus membranaceus Source: Alternative Medicine Foundation, Inc.; www.amfoundation.org Berberis Alternative names: Barberry; Berberis sp. Source: Alternative Medicine Foundation, Inc.; www.amfoundation.org Brewer's Yeast Source: Healthnotes, Inc.; www.healthnotes.com Bromelain Alternative names: Ananas comosus Source: Integrative Medicine Communications; www.drkoop.com Bromelainum Alternative names: Bromelain Source: Integrative Medicine Communications; www.drkoop.com Cobalamin Alternative names: Vitamin B12 (Cobalamin) Source: Integrative Medicine Communications; www.drkoop.com Doxycycline Source: Healthnotes, Inc.; www.healthnotes.com Guggul Alternative names: Commiphora mukul Source: Healthnotes, Inc.; www.healthnotes.com Helidac Source: Healthnotes, Inc.; www.healthnotes.com Hydrastis Alternative names: Goldenseal; Hydrastis canadensis L. Source: Alternative Medicine Foundation, Inc.; www.amfoundation.org
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Hypericum Perforatum Source: Integrative Medicine Communications; www.drkoop.com Klamathweed Source: Integrative Medicine Communications; www.drkoop.com Minocycline Source: Healthnotes, Inc.; www.healthnotes.com Probiotics Source: Healthnotes, Inc.; www.healthnotes.com Psyllium Source: WholeHealthMD.com, LLC.; www.wholehealthmd.com Hyperlink: http://www.wholehealthmd.com/refshelf/substances_view/0,1525,814,00.html St. John's Wort Alternative names: Hypericum perforatum, Klamathweed Source: Integrative Medicine Communications; www.drkoop.com St. John's Wort Source: WholeHealthMD.com, LLC.; www.wholehealthmd.com Hyperlink: http://www.wholehealthmd.com/refshelf/substances_view/0,1525,824,00.html Tetracycline Source: Healthnotes, Inc.; www.healthnotes.com Tetracycline Derivatives Source: Integrative Medicine Communications; www.drkoop.com Tetracyclines Source: Healthnotes, Inc.; www.healthnotes.com Tetracyclines Source: Prima Communications, Inc.www.personalhealthzone.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 TETRACYCLINE Overview In this chapter, we will give you a bibliography on recent dissertations relating to tetracycline. 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 “tetracycline” (or a synonym) in their titles. To accurately reflect the results that you might find while conducting research on tetracycline, we have not necessarily excluded nonmedical dissertations in this bibliography.
Dissertations on Tetracycline 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 tetracycline. You will see that the information provided includes the dissertation’s title, its author, and the institution with which the author is associated. The following covers recent dissertations found when using this search procedure: •
A study of the bone formation kinetics : biorhythmicity demonstrated by tetracycline labelling by Tam, Cherk S; PhD from University of Toronto (Canada), 1976 http://wwwlib.umi.com/dissertations/fullcit/NK35143
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Interaction of the tetracycline resistance protein Tet(O) with the bacterial ribosome by Connell, Sean Robert C.; PhD from University of Alberta (Canada), 2003, 230 pages http://wwwlib.umi.com/dissertations/fullcit/NQ82089
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Isolation and molecular characterization of the Drosophila tetracycline transporter by Orlichenko, Lidiya S.; PhD from University of Notre Dame, 2003, 130 pages http://wwwlib.umi.com/dissertations/fullcit/3078964
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Mechanisms of streptomycin and tetracycline resistance in Pseudomonas aeruginosa by Tseng, Jui-Teng; PhD from University of Alberta (Canada), 1973 http://wwwlib.umi.com/dissertations/fullcit/NK15369
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Towards the synthesis of (-)-tetracycline; development of an approach initiated by the microbial dihydroxylation of benzoic acid by Siegel, Dionicio Rhodes; PhD from Harvard University, 2003, 267 pages http://wwwlib.umi.com/dissertations/fullcit/3091687
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 TETRACYCLINE 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 “tetracycline” (or a synonym) in their titles. To accurately reflect the results that you might find while conducting research on tetracycline, we have not necessarily excluded nonmedical patents in this bibliography.
Patents on Tetracycline By performing a patent search focusing on tetracycline, 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 tetracycline: •
4-dedimethylaminotetracycline derivatives Inventor(s): Ashley; Robert A. (63 Woodhill Rd., Newtown, PA 18940), Hlavka; Joseph J. (Tower Hill Rd., Tuxedo Park, NY 10987) Assignee(s): None Reported Patent Number: 6,506,740 Date filed: May 18, 2000 Abstract: The present invention provides new chemically modified 4dedimethylaminotetracycline compounds that can be substituted at the 7, 8, and/or 9 positions and methods for preparing the 4-dedimethylamino tetracycline compounds. Other tetracycline compounds are the 4-dedimethylaminotetracycline derivatives with an oxime group, NH-Alkyl, or N--NH-Alkyl group at the C4 position. The present invention also provides a method of treating a mammal suffering from conditions or diseases by administering to the mammal an effective amount of the new chemically modified 4-dedimethylamino tetracycline compounds. Excerpt(s): The present invention relates to novel 4-dedimethylaminotetracycline derivatives, methods for producing the novel derivatives and methods of using these derivatives. Tetracycline as well as the 5-OH (Terramycin) and 7-Cl (Aureomycin) derivatives exist in nature, and are well known antibiotics. Natural tetracyclines may be modified without losing their antibiotic properties, although certain elements of the structure must be retained. The modifications that may and may not be made to the basic tetracycline structure have been reviewed by Mitscher in The Chemistry of Tetracyclines, Chapter 6, Marcel Dekker, Publishers, New York (1978). According to Mitscher, the substituents at positions 5-9 of the tetracycline ring system may be modified without the complete loss of antibiotic properties. Changes to the basic ring system or replacement of the substituents at positions 1-4 and 10-12, however, generally lead to synthetic tetracyclines with substantially less or effectively no antimicrobial activity. Some examples of chemically modified non-antimicrobial tetracyclines (hereinafter CMT) include 4-dedimethylaminotetracyline, 4-dedimethylaminosancycline (6-demethyl-6-deoxy-4-dedimethylaminotetracycline), 4-dedimethylaminominocycline (7-dimethylamino-4-dedimethylaminotetracycline), and 4-dedimethylaminodoxycycline (5-hydroxy-6-deoxy-4-dedimethyaminosancycline). Some 4-dedimethylaminotetracyline derivatives are disclosed in U.S. Pat. Nos. 3,029,284 and 5,122,519. They include 6demethyl-6-deoxy-4-dedimethylaminotetracycline and 5-hydroxy-6-deoxy-4dedimethylaminotetracycline with hydrogen and other substituents at the C7, and the C9 positions on the D ring. These substituents include amino, nitro, di(lower alkyl)amino, and mono(lower alkyl)amino or halogen. The 6-demethyl-6-deoxy-4dedimethylaminotetracycline derivatives and 5-hydroxy-6-deoxy-4dedimethylaminotetracycline derivatives are said to be useful as antimicrobial agents. Web site: http://www.delphion.com/details?pn=US06506740__
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7, 9-substituted tetracycline compounds Inventor(s): Bhatia; Beena (Arlington, MA), Bowser; Todd (Charlton, MA), Frechette; Roger (Reading, MA), Hawkins; Paul (Cambridge, MA), Ismail; Mohamed (Bedford, MA), McIntyre; Laura (Arlington, MA), Nelson; Mark L. (Wellesley, MA), Reddy; Laxma (Lexington, MA), Sheahan; Paul (Hopkinton, MA), Stapleton; Karen (Weymouth, MA), Viski; Peter (Brookline, MA), Warchol; Tad (Acton, MA) Assignee(s): Paratek Pharmaceuticals, Inc. (boston, Ma) Patent Number: 6,683,068 Date filed: June 29, 2001 Abstract: The present invention pertains to novel 7,9-substituted tetracycline compounds. These tetracycline compounds can be used to treat numerous tetracycline compound-responsive states, such as bacterial infections and neoplasms, as well as other known applications for minocycline and tetracycline compounds in general, such as blocking tetracycline efflux and modulation of gene expression. Excerpt(s): The development of the tetracycline antibiotics was the direct result of a systematic screening of soil specimens collected from many parts of the world for evidence of microorganisms capable of producing bacteriocidal and/or bacteriostatic compositions. The first of these novel compounds was introduced in 1948 under the name chlortetracycline. Two years later, oxytetracycline became available. The elucidation of the chemical structure of these compounds confirmed their similarity and furnished the analytical basis for the production of a third member of this group in 1952, tetracycline. A new family of tetracycline compounds, without the ring-attached methyl group present in earlier tetracyclines, was prepared in 1957 and became publicly available in 1967; and minocycline was in use by 1972. Recently, research efforts have focused on developing new tetracycline antibiotic compositions effective under varying therapeutic conditions and routes of administration. New tetracycline analogues have also been investigated which may prove to be equal to or more effective than the originally introduced tetracycline compounds. Examples include U.S. Pat. Nos. 2,980,584; 2,990,331; 3,062,717; 3,165,531; 3,454,697; 3,557,280; 3,674,859; 3,957,980; 4,018,889; 4,024,272; and 4,126,680. These patents are representative of the range of pharmaceutically active tetracycline and tetracycline analogue compositions. Historically, soon after their initial development and introduction, the tetracyclines were found to be highly effective pharmacologically against rickettsiae; a number of grampositive and gram-negative bacteria; and the agents responsible for lymphogranuloma venereum, inclusion conjunctivitis, and psittacosis. Hence, tetracyclines became known as "broad spectrum" antibiotics. With the subsequent establishment of their in vitro antimicrobial activity, effectiveness in experimental infections, and pharmacological properties, the tetracyclines as a class rapidly became widely used for therapeutic purposes. However, this widespread use of tetracyclines for both major and minor illnesses and diseases led directly to the emergence of resistance to these antibiotics even among highly susceptible bacterial species both commensal and pathogenic (e.g., pneumococci and Salmonella). The rise of tetracycline-resistant organisms has resulted in a general decline in use of tetracyclines and tetracycline analogue compositions as antibiotics of choice. Web site: http://www.delphion.com/details?pn=US06683068__
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Antibiotic composition for inhibition of angiogenesis Inventor(s): Bok; Robert A. (#158, 3121 Chowen Ave. South, Minneapolis, MN 55416), Brem; Henry (11201 Five Springs Rd., Lutherville, MD 21093), Tamargo; Rafael J. (2306 Pennyroyal Ter., Baltimore, MD 21209) Assignee(s): None Reported Patent Number: 6,482,810 Date filed: April 13, 1994 Abstract: Pharmaceutical compositions for delivering an effective dose of an angiogenesis inhibitor consisting of a tetracycline or tetracycline such as minocycline. The effective dosage for inhibition of angiogenesis based on in vitro testing is between one and 500 micromolar. The compositions are delivered topically, locally or systemically using implants or injection. The composition is extremely selective for growth of endothelial cells, inhibiting growth, but is not cytotoxic at the effective dosages. Excerpt(s): This invention is in the field of angiogenesis inhibitors, in particular antibiotics that inhibit angiogenesis. Angiogenesis, the proliferation and migration of endothelial cells that result in the formation of new blood vessels, is an essential event in a wide variety of normal and pathological processes. For example, angiogenesis plays a critical role in embryogenesis, wound healing, psoriasis, diabetic retinopathy, and tumor formation, as reported by Folkman, J. Angiogenesis and its inhibitors. In: V. T. DeVita, S. Hellman and S. A. Rosenberg (eds.). Important Advances in Oncology, pp. 42-62, (J. B. Lippincott Co., Philadelphia, 1985); Brem, H., et al., Brain tumor angiogenesis. In: P. L. Kornblith and M. D. Walker (eds.), Advances in Neuro-Oncology, pp. 89-101. (Future Publishing Co., Mount Kisco, N.Y. 1988); Folkman, J. Tumor angiogenesis: therapeutic implications. N. Engl. J. Med., 285; 1182-1186 (1971); and Folkman, J. Successful treatment of an angiogenic disease. N. Engl. J. Med., 320: 1211-1212 (1989). Identification of several agents that inhibit tumor angiogenesis has provided a conceptual framework for the understanding of angiogenesis in general. The inhibition of angiogenesis by certain steroids and heparin derivatives, reported by Folkman, J., et al., Science 221: 719. (1983); and Murray, J. B., et al., Purification and partial amino acid sequence of a bovine cartilage-derived collagenase inhibitor. J. Biol. Chem., 261: 4154-4159 (1986); led to studies elucidating the crucial role of remodeling of the extracellular matrix in angiogenesis. These agents apparently prevent angiogenesis by specifically disrupting the deposition and cross-linking of collagen, as reported by Ingber, D., and Folkman, J. Inhibition of angiogenesis through modulation of collagen metabolism. Lab. Invest., 59: 44-51 (1989). Web site: http://www.delphion.com/details?pn=US06482810__
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Antibiotic treatment of age-related macular degeneration Inventor(s): Wirostko; Emil (34 Old Mine Rd., Lebanon, NJ 08833) Assignee(s): None Reported Patent Number: 6,015,803 Date filed: May 5, 1998 Abstract: A method is provided for the treatment of age-related macular degeneration by administering various antibiotics, such as tetracycline and its derivatives, rifamycin
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and its derivatives, macrolides, and metronidazole, to a patient in a therapeutically effective amount. Excerpt(s): The present invention is directed to the treatment of age-related macular degeneration (ARMD) by the administration of certain antibiotics. In one embodiment, broad-spectrum bacteriostatic antibiotics, such as tetracycline-based antibiotics (TBA), are administered for up to fourteen (14) months, which leads to measurable improvements in some of the symptoms. Age-related macular degeneration (ARMD) is the leading cause of blindness among persons over fifty in the United States and other countries (Bressler NM et al., Age-related macular degeneration. Sury. Ophthalmol. 1988; 32: 375-413). Two forms of age-related macular degeneration are known: (1) neovascular, also known as exudative, age-related macular degeneration (E-ARMD) and (2) nonneovascular, also known as nonexudative, age-related macular degeneration (NE-ARMD). NE-ARMD is characterized by the presence of drusen, yellow-white lesions of the retinal pigment epithelium within the macula, and by other abnormalities of the retinal pigment epithelium, including retinal cell death. Although the exact etiology of ARMD is not known, several risk factors seem to be important for the manifestation of this disease. For example, ARMD may be caused by chronic exposure of the retina to light. The presence or absence of certain nutrients in the diet, such as the antioxidant vitamins E and C, also may affect one's predisposition for ARMD. Other conditions, such as hypertension and smoking, are also considered to be important risk factors for the development of this disease. Web site: http://www.delphion.com/details?pn=US06015803__ •
Antibiotic/medicated gutta percha point Inventor(s): Martin; Howard (11500 W. Hill Dr., Rockville, MD 20852) Assignee(s): None Reported Patent Number: 6,602,516 Date filed: November 2, 2000 Abstract: The ability to incorporate iodoform, tetracycline and a combination of iodoform/tetracycline into root canal gutta percha points is described. The iodoform, tetracycline and iodoform/tetracycline combination are bound within the gutta percha points. They act as a reservoir of antimicrobial that is capable of diffusing onto the surface of the gutta percha thereby inhibiting the colonization of bacteria on the gutta percha points and within the root canal system. Tetracycline is capable of coalescing within the dentinal tubules to inhibit long term microbial growth. These medicated gutta percha points are site specific, surface acting antimicrobial gutta percha points.A method of the usage and delivery of amorphous form iodoform gutta percha, iodoform/tetracycline gutta percha, or tetracycline gutta percha within a heated compule with a pressure plunger by delivering the thermo-softened heat labile amorphous form via a pressure extrusion system through a cannula into the prepared root canal system. Excerpt(s): The present invention relates to antibacterial gutta percha for obturation of root canals and, more particularly, to an improved gutta percha point comprising tetracycline and/or iodoform and method for application of the same that yields a broader spectrum of effectiveness based upon the clinical symptomatology in combating the bacterial contamination of leakage and reinfection. The method for application allows the dentist to chose the properly medicated gutta percha point for the individual
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case. The aim of endodontic treatment is the elimination of infection from the root canal and the prevention of reinfection within the root canal. Bacteria have long been recognized as the primary etiologic agent of reinfection within the root canal. Proper obturation of the root canal space is a key to this success. According to the Washington University study nearly 60% of the failures studied occurred because of canal leakage. Salivary fluid, apical fluids, and leakage infiltration due to open lateral canals because of periodontal disease, all contribute to leakage failure and subsequent reinfection of the root canal. Web site: http://www.delphion.com/details?pn=US06602516__ •
Anti-inflammatory composition comprising tetracycline Inventor(s): Gardner; Wallace J. (1791 Mass Ave., Cambridge, MA 02140) Assignee(s): None Reported Patent Number: 6,610,274 Date filed: December 18, 2001 Abstract: Therapeutic composition having anti-infective activity. The therapeutic composition is a formulation comprising an antibiotic, preferably a tetracycline, most preferably doxycycline, which has not been chemically modified to eliminate antimicrobial efficacy. The antibiotic is preferably in a liquid vehicle, most preferably one that contains at least 20% alcohol by volume. The therapeutic composition is preferably in local delivery form and is self-administered orally or via the nasal cavity. Administration of the therapeutic composition of the present invention treats diseases that originate from the oral cavity or that do not originate in the oral cavity, but are affected by contaminants, such as viruses or bacteria, in the oral cavity entering the bloodstream including but not limited to periodontal disease, sinusitis, gingivitis, the common cold, sore throat, influenza, allergies (particularly to tree pollen), resistant pneumonia, diseases of the gastrointestinal tract, inflammatory diseases such as rheumatoid arthritis, cancer, ulcers, heart disease, etc. Excerpt(s): The accumulation bacteria in the oral cavity, such as on the teeth or tongue has been identified as a contributor or cause of various inflammatory conditions, including gingivitis, periodontitis and other gum diseases. Treatment of the oral cavity with antibiotics to reduce or eliminate the effects of bacteria is known. For example, broad spectrum antibiotics such as tetracyclines and metronidazole have been used in the treatment of periodontal disease to reduce oral cavity microflora. Typically such use has been systemic, which can result in various undesirable side effects, including the threat or danger or building allergies or immunity to the antibiotic, overgrowth of opportunistic yeast and fungi and intestinal disturbances. Many other common inflammatory diseases, such as sinusitis, diseases of the gastrointestinal tract (including those that manifest themselves in stomach and bowel problems), the common cold, influenza, allergies, halitosis, pneumonia, etc., also may be caused by viruses and/or bacteria. Often the source of the bacteria and viruses is the oral cavity, especially the ear, nose and throat passages, and the sinuses. Once the bacteria and/or viruses are resident in the oral cavities or sinuses (e.g., the maxillary, frontal and ethmoid), they can continually cause infection through circulation in the blood stream. Continual reduction or elimination of these bacteria and viruses would reduce chronic infection in the body. The problems of the prior art have been overcome by the present invention, which provides a therapeutic composition having anti-infective activity. In a preferred embodiment, the therapeutic composition is a formulation comprising an antibiotic,
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preferably a tetracycline, most preferably doxycycline, which has not been chemically modified to eliminate antimicrobial efficacy. The antibiotic is preferably in a liquid vehicle, most preferably one that contains at least 20% alcohol by volume. The therapeutic composition is preferably in local delivery form and is preferably selfadministered orally or via-the nasal cavity. The therapeutic composition most preferably is a self-delivered formulation in local delivery form that consists essentially of a tetracycline, most preferably doxycline, which has not been chemically modified to eliminate antimicrobial efficacy, and a liquid vehicle, more preferably one which contains at least 20% alcohol by volume, and most preferably one which consists essentially of sterile water or Listerine or the like, which tetracyline is preferably present in the formulation in the amount of between 50 to 100 mgs per ounce of liquid vehicle. Web site: http://www.delphion.com/details?pn=US06610274__ •
Combination of bisphosphonate and tetracycline Inventor(s): Golub; Lorne M. (Smithtown, NY), Ramamurthy; Nungavarm S. (Smithtown, NY), Salo; Tuula A. (Oulu, FI), Sorsa; Timo A. (Helsinski, FI), Teronen; Olli P. (Helsinski, FI) Assignee(s): Research Foundation of S.u.n.y. (albany, Ny) Patent Number: 6,114,316 Date filed: September 2, 1999 Abstract: Tissue-destructive conditions related to excess protemase activity in a biological system are treated or prevented by administering to the system a composition which combines a tetracycline and a bisphosphonate in synergistic proteinase inhibiting amounts. Excerpt(s): This invention was made with government support under R37DE03987 awarded by the National Institute of Dental Research (NIH). The government has certain rights in the invention. The invention relates to a combination of tetracyclines and bisphosphonates which act synergistically to inhibit, reduce, down-regulate and/or prevent degradation of connective tissue, basement membrane as well as other factors in subjects susceptible to this type of tissue degradation. Proteolytic activity is responsible for damage to connective tissues and basement membranes as a complication of the inflammatory and/or immune response and other disease processes, such as cancer cell invasion and metastasis. The inflammatory response contributes, for example, to the pathological changes in a number of acute and chronic processes involving diverse organs and tissues such as the lungs, bone, heart, joints, skin and periodontium, etc. Web site: http://www.delphion.com/details?pn=US06114316__
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Conditionally controlled, attenuated HIV vaccine Inventor(s): Smith; Stephen M. (Essex Fells, NJ) Assignee(s): Infectious Diseases Foundation (essex Fells, Nj) Patent Number: 6,541,003 Date filed: July 25, 2000 Abstract: A live attenuated human immunodeficiency virus type 1 (HIV-1) whose replication is not constitutive but is instead conditionally regulated (such that rounds of
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reverse transcription with accompanying potential for error are strictly limited) might yield a paradigm that minimizes evolution to virulence and facilitate vaccine development. We have broached the concept of conditional control of HIV-1 through gain-of-function. Here, we describe the design of constitutively inactive HIV-1 genomes (HIV-DoxT and HIV-DoxSp) which can be conditionally resuscitated to an active state by tetracycline or related analogues. The HIV-DoxT construct comprises an inactivating mutation engineered into TAR, thereby rendering the virus non-responsive to Tat, a 302bp DNA fragment (TetopT) which contains the tet-operator ligated into a position upstream of the HIV TATAA box, in both the 5' and 3' LTRs, and a reverse tetracyclinecontrolled activator (RTTA) coding sequence in place of the nef coding region. The HIVDoxSp construct contains three additional Sp1 sites in the TetopT promoter upstream of the TATAA box thereby generating the promoter TetopSp. Genotypically, HIVDoxT is tat(+)tar(-)nef(-)Sp1(-) and HIVDoxSp is tat(+)tar(-)nef(-)Sp1(+). Since both genomes are genetically tar(-), they would ordinarily be expected to be wholly defective in producing viral proteins and/or particles. However, following transfection into an appropriate cell target, both proviruses, in a doxycycline-dependent fashion, capably released Gag and RT from cells. In the absence of doxycycline, no replication competent virus could be recovered. These findings suggest that the heterologous RTTA+Dox mechanism substituted effectively for Tat/TAR. These constructs should prove useful in the development of HIV-specific immunological and diagnostic reagents. Excerpt(s): This invention relates to the field of vaccines. More particularly, this invention is directed to a process for controlling the expression of an HIV provirus to produce a doxycycline-inducible HIV genome. The genome may be used in attenuated HIV vaccines. Vaccination and immunization generally refer to the introduction of a non-virulent agent against which an individual's immune system can initiate an immune response which will then be available to defend against challenge by a pathogen. The immune system identifies invading "foreign" compositions and agents primarily by identifying proteins and other large molecules which are not normally present in the individual. The foreign protein represents a target against which the immune response is made. The immune system can provides multiple means for eliminating targets that are identified as foreign. These means include humoral and cellular responses which participate in antigen recognition and elimination. Briefly, the humoral response involves B cells which produce antibodies that specifically bind to antigens. There are two arms of the cellular immune response. The first involves helper T cells which produce cytokines and elicit participation of additional immune cells in the immune response. The second involves killer T cells, also known as cytotoxic T lymphocytes (CTLs), which are cells capable of recognizing antigens and attacking the antigen including the cell or particle it is attached to. Web site: http://www.delphion.com/details?pn=US06541003__ •
Double capsule for the administration of active principles in multiple therapies Inventor(s): Sanso; Giovanni (Milan, IT) Assignee(s): Axcan Pharma Inc. (quebec, Ca) Patent Number: 6,350,468 Date filed: June 16, 2000 Abstract: A pharmaceutical dosage form particularly suitable for the administration of active principles in multiple therapies is disclosed. The pharmaceutical dosage form is a double capsule where in an internal capsule is placed inside an external one. Each
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internal and external capsule includes one or more active principles. A double capsule according to the invention is preferably used in triple or quadruple therapies against the microorganisms Helicobacter Pylori. Advantages of this pharmaceutical dosage form consist in providing a simple posology for administration of two and more active principles, allowing the active principles to activate at the right intervals of time and in the preestablished quantities, and preventing interactions between active principles. In a preferred embodiment of the invention, the pharmaceutical dosage form has an external capsule containing bismuth subcitrate and metronidazole, and an internal capsule containing tetracycline and optionally omeprazole, which is used in therapy for eradication of Helicobacter pylori. Excerpt(s): This invention concerns a pharmaceutical dosage form consisting of a double capsule for the administration of active principles in multiple therapies. The double capsule consists in a capsule placed inside another one. Therapies for the administration of more than one active principle at a time or at short intervals of time are already well known. The most common pharmaceutical dosage form consists of tablets for the various active principles with coatings allowing the differentiated release of the chemical compounds. Among said therapies, the most common ones are those concerning affections of the digestive system caused by the presence of the microorganisms Helicobacter Pylori, such as gastritis and gastroduodenal ulcers, which in due time can lead to tumoral forms. As known, Helicobacter pylori is a modern appellation of Campilobacter pylori. Web site: http://www.delphion.com/details?pn=US06350468__ •
Enhancing the toxicity of warfarin in rodents Inventor(s): Poche; Richard M. (Wellington, CO) Assignee(s): Reckittt Benckiser Inc. (wayne, Nj) Patent Number: 6,248,730 Date filed: February 3, 1999 Abstract: The presence of a small amount of an antibiotic, such as tetracycline or a salt or derivative thereof, in warfarin-containing rodent baits enhances the toxicity of warfarin against rodents which have heretofore shown apparent resistance to warfarin. Excerpt(s): This invention relates to methods for enhancing the toxicity of warfarin in rodenticidal compositions and to warfarin-containing rodenticidal compositions which are effective against warfarin-resistant rodents. has, since the 1950s been in use as an active ingredient in rodenticidal compositions. In addition to its use as a rodenticide, warfarin is also used, in generally smaller amounts, in humans to provide similar anticoagulating effects. The basis for the effectiveness of warfarin as a rodenticide lies in the fact that it is effective in small, multiple doses. One or two doses of the compound are seldom fatal if taken at the recommended concentration; thus the hazard of acute toxicity to man, domestic animals, and wildlife is greatly reduced. In practical use, warfarin has been sold as a "concentrate" containing 0.5 percent of the active ingredient. This is diluted for use with a suitable bait, to a concentration of about 0.025 percent. Baits commonly used are cereal products, corn meal, rolled oats, mixed animal feeds, and similar products. Baits containing warfarin can be placed in stations and left there for considerable periods of time, so that the rodent populations may partake of several doses in sequence. Usually the rodents begin to die after four or five daily doses of the materials, and the population is greatly reduced or eradicated in approximately three
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weeks. Death is caused by hemorrhages, brought about by the action of the warfarin in reducing the clotting power of the blood. These hemorrhages may be external or internal and can be initiated by very slight injury or capillary damage. One of the other advantages of warfarin is that, because multiple ingestions are required to kill the rodents, they do not develop bait shyness. Web site: http://www.delphion.com/details?pn=US06248730__ •
Expression vector for consistent cellular expression of the tet on repressor in multiple cell types Inventor(s): Fisher; Paul B. (Scarsdale, NY), Gopalkrishnan; Rahul (New York, NY) Assignee(s): The Trustees of Columbia University in the City of New York (new York, Ny) Patent Number: 6,440,741 Date filed: March 15, 1999 Abstract: A vector having the Protein Translation Peptide Elongation Factor-1.alpha. (EF-1.alpha.) promoter and nucleic acids encoding a reverse tetracycline-controlled activator is provided, wherein the expression of the activator is under the control of the EF-1.alpha. promoter. In addition, a method of generating a reverse tetracyclinecontrolled transactivator expression system for inducible tetracycline-regulated gene expression is provided that consists of: (a) isolation of a DNA fragment encoding the reverse tetracycline-controlled transactivator, (b) isolation of a DNA fragment containing the EF-1.alpha. promoter, (c) subcloning of these DNA fragments into a plasmid or other suitable vector to create a vector in which the reverse tetracyclinecontrolled transactivator is operably linked to the EF-1.alpha. promoter. Excerpt(s): Throughout this application, various publications are referenced. The disclosures of these publications in their entireties are hereby incorporated by reference in order to more fully describe the state of the art as known to those skilled therein as of the date of the invention described and claimed herein. Since the first report by Gossen and Bujard (Gossen and Bujard, 1992) and subsequent documentation of a variant form (Gossen et al., 1995), the Tetracycline (Tc)-regulated system, has been broadly adopted and is widely acknowledged as the method of choice, in experiments requiring inducible expression of genes of interest. In its originally reported form, the system employs two plasmids. One expressing the tTA or rtTA cDNA (henceforth jointly referred to as TA), a fusion protein of the bacterial Tc-repressor, fused to the C-terminal acidic activation domain of the Herpes Simplex virus (HSV), VP16 transcriptional transactivator. The second plasmid enables cloning of a cDNA of interest downstream of a heptamerized Tc-operator transcription regulatory DNA sequence, fused to a DNA element providing basal promoter activity, derived either from the CMV IE or HSV thymidine kinase promoters Establishing a cell line having Tc-regulatable expression of the gene of interest involves a two step process. In the first, a cell line stably expressing the TA cDNA is established and identified by clonal selection and expression analysis through transient transfection with a Tc-responsive reporter. In the second step, the gene of interest cloned under control of the Tc-responsive element is introduced into the cell line made in the previous step and a second round of selection is performed to identify clones displaying Tc-responsive inducibility of the cDNA (Gossen and Bujard, 1992; Gossen et al., 1995). The Tc-regulated system has effectively overcome several drawbacks seen in earlier systems which showed high basal levels of expression, poor responsiveness and toxicity of the inducing agent. The Tc-inducible system is in
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addition, able to achieve induction over ranges of several orders of magnitude in a graded manner, responsive to varying levels of inducer. Furthermore, the system is extremely versatile and amenable to several types of modifications, permitting the study of the role of a particular gene, or combinations thereof, in a wide variety of cell types of interest. The potential to use this system in medical applications including gene therapy protocols and pharmacological small molecule screening are areas of active investigation. Its versatility has enabled adaptation to situations requiring inducible gene expression in a tissue specific or generalized manner in animal or plant models, opening new avenues to study gene function in vivo. The Tc-inducible expression system has been modified in several ways, in attempts to improve performance or tailor it to specific needs. Autoregulatory control was achieved by placing both the tTA as well as exogenous cDNA under control of Tc-operator sequences (Shocket et al., 1995), which reportedly permitted regulation of available tTA levels only on induction and thereby increased overall performance in terms of inducibility and frequency of positive clones obtained. Single plasmid vectors containing the tTA sequence and gene of interest in opposite orientations have been developed to obviate the need for multiple rounds of clonal selection (Baron et al., 1995; Schultze et al., 1996; Weinmann et al., 1994). Overcoming a sometimes considerable barrier of introduction of DNA into transfection recalcitrant cells has been made possible through the development of retroviral vectors for delivery of both components of the system in either a single or combination of two separate viruses (Bohl et al., 1997; Hofmann et al., 1996; Kringstein et al., 1998; Paulus et al., 1996; Rossi et al., 1998). Several promoters have been used to enable generalized or tissue specific expression of tTA in plants (Weinmann et al., 1994) or animals (Efrat et al., 1995; Fishman et al., 1994; Furth et al., 1994; Hennighausen et al., 1995). Modification of the Tc-operator containing plasmid to reduce leaky expression or reduce the effects of integration site has been attempted. Strategies toward this end include Epstein Barr virus (EBV) replication origin based vectors that are maintained episomally (Jost et al., 1997), modified basal promoters to reduce uninduced expression (Hoffmann et al., 1997) and incorporation of sequences that prevent interference from adjoining elements at the site of integration (Hennighausen et al., 1995; McKnight et al., 1992; Stief et al., 1989). Web site: http://www.delphion.com/details?pn=US06440741__ •
Formulations for treating or preventing mucositis Inventor(s): Comiskey; Stephen J. (Doylestown, PA), Lawter; James Ronald (Yardley, PA) Assignee(s): Orapharma, Inc. (warminster, Pa) Patent Number: 6,683,067 Date filed: March 23, 2001 Abstract: Mucositis is treated and/or prevented by administrating to a patient a formulation comprising a tetracycline that is poorly absorbed from the gastro-intestinal tract. The tetracycline may be in the form of a pharmaceutically acceptable salt or a base. The formulations may optionally also contain an antifungal agent to prevent fungal overgrowth due to reduction in the normal oral flora by the tetracycline. Such compositions have the advantage of treating the entire gastro-intestinal tract since the active ingredient is not removed from the tract via absorption. Further, such compositions minimize systemic exposure and accompanying side effects. Excerpt(s): The present application relates generally to formulations containing a tetracycline that are useful for treating or preventing mucositis. Mucositis is a dose-
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limiting side effect of cancer therapy and bone marrow transplantation and is not adequately managed by current treatment (Sonis, 1993a, "Oral Complications," in: Cancer Medicine, pp. 2381-2388, Holand et al.; Eds., Lea and Febiger, Philadelphia; Sonis, 1993b, "Oral Complications in Cancer Therapy," In: Principles and Practice of Oncology, pp. 2385-2394, De Vitta et al., Eds., J. B. Lippincott, Philadelphia). Oral mucositis is found in almost 100% of patients receiving radiotherapy for head and neck tumors, in about 40% of patients receiving chemotherapy, and in about 90% of children with leukemia (Sonis, 1993b, supra). Complications related to oral mucositis, though varying in the different patient populations, generally include pain, poor oral intake with consequent dehydration and weight loss, and systemic infection with organisms originating in the oral cavity leading to septicemia (Sonis, 1993b; U.S. Pat. No. 6,025,326 to Steinberg et al.). In addition to the oral cavity, mucositis may also affect other parts of the gastro-intestinal tract. A variety of approaches to the treatment of oral mucositis and associated oral infections have been tested with limited success. For example, the use of an allopurinol mouthwash, an oral sucralfate slurry, and pentoxifyline were reported in preliminary studies to result in a decrease in mucositis. Subsequent randomized and controlled studies, however, have failed to demonstrate any benefit from treatment with these agents (Loprinzi et al., 1995, Sem. Oncol. 22 Suppl. 3): 95-97; Epstein & Wong, 1994, Int. J. Radiation Oncology Biol. Phys. 28:693-698; Verdi et al., 1995, Oral Surg. Oral Med. Oral Pathol. Oral Radiol. Endod. 80:36-42). Web site: http://www.delphion.com/details?pn=US06683067__ •
Inducible expression system Inventor(s): Chen; Shin-Tai (San Diego, CA), Friedmann; Theodore (La Jolla, CA), Yee; Jiing-Kuan (Del Mar, CA) Assignee(s): City of Hope (duarte, Ca), The Regents of the University of California (oakland, Ca) Patent Number: 6,133,027 Date filed: August 7, 1996 Abstract: The present invention features compositions and methods for the inducible expression of a polypeptide, especially a polypeptide normally cytotoxic to the eukaryotic host cell in which it is to be expressed. A nucleotide sequence encoding a polypeptide of interest is operably linked to an inducible promoter (e.g, a promoter composed of a minimal promoter linked to multiple copies of tetO, the binding site for the tetracycline repressor (tetR) of the Escherichia coli tetracycline resistance operon Tn10). Expression from the inducible promoter is regulated by a multi-chimeric transactivating factor, composed of a first ligand-binding domain that negatively regulates transcription (e.g., a prokaryotic tetracycline repressor polypeptide), a transcriptional activation domain, and a second ligand-binding domain that positively regulates the transcriptional activation function of the transactivator (e.g., a ligandbinding domain of a steroid receptor, preferably an estrogen receptor (ER)). Transcription of the nucleotide sequence under control of the inducible promoter is activated by the multi-chimeric transactivator when both the ligand that binds the first ligand-binding domain (e.g., tetracycline) is absent and the ligand that binds the second ligand-binding domain (e.g., a steroid) is present. This inducible expression system is particularly useful in the expression of the cytotoxic protein VSV G for the production of pseudotyped retroviral vectors.
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Excerpt(s): This invention relates generally to the field of recombinant retroviral particles for use in gene delivery, e.g., for use in gene therapy. Retroviruses are enveloped RNA viruses that, after infection of a host cell, reverse transcribe their RNA genomes into a DNA intermediate, or provirus. The provirus can be stably integrated into the host's cellular DNA. Gene products encoded by the provirus are then expressed by the host cell to produce retroviral virions, thereby replicating the virus. Because the retroviral genome can be manipulated to include exogenous nucleotide sequence(s) of interest for expression in a target cell, retroviral vectors are important tools for stable gene transfer into mammalian cells. Many proposed gene therapy applications use retroviral vectors to take advantage of the ability of these naturally infectious agents to transfer and efficiently express recombinant nucleotide sequences in susceptible target cells (see, e.g., Miller 1992 Nature 357:455-460; Miller Curr. Top. Microbiol. Immunol. 158:1-24). Retroviral vectors suitable for use in such applications are generally defective retroviral vectors that are capable of infecting the target cell, reverse transcribing their RNA genomes, and integrating the reverse transcribed DNA into the target cell genome, but are incapable of replicating within the target cell to produce infectious retroviral particles (e.g., the retroviral genome transferred into the target cell is defective in gag, the gene encoding virion structural proteins, and/or in pol, the gene encoding reverse transcriptase). Use of retroviral vectors is limited in many aspects. For example, although retroviruses can efficiently infect and stably integrate into the genome of rapidly-dividing cells, retroviral integration into the genome of non-dividing or slowly dividing cells is inefficient (springett et al. 1989 J. Virol. 63:3865-3869; Miller et al. 1990 Mol. Cell. Biol. 10:4239-4242; Roe et al. 1993 EMBO J. 12:2099-2108). Most packaging systems provide only modest vector titers, and the fragility of retroviral vector particles complicate purification and concentration (Paul et al. 1993 Hum. Gene Therap. 4:609615). Finally, retroviruses enter target cells by binding of retroviral envelope glycoproteins (encoded by the env gene) to specific target cell surface receptors. This envelope protein-cell surface receptor interaction is often species specific, and in some cases even tissue specific. Moreover, the level of expression of the cell surface receptor on the target cells can vary widely among target cells. As a result, retroviruses usually have a limited host range (Kavanaugh et al. 1994 Proc. Natl. Acad. Sci. USA 91:70717075; Hopkins 1993 Proc. Natl. Acad. Sci. USA 90:8759-8760). Web site: http://www.delphion.com/details?pn=US06133027__ •
Inhibition of excessive phospholipase A.sub.2 activity and/or production by nonantimicrobial tetracyclines Inventor(s): Golub; Lorne M. (Smithtown, NY), Greenwald; Robert A. (Melville, NY), McNamara; Thomas F. (Port Jefferson, NY), Pruzanski; Waldemar (Toronto, CA), Ramamurthy; Nangavarum S. (Smithtown, NY), Vadas; Peter (Toronto, CA) Assignee(s): The Research Foundation of State Univ. of New York (albany, Ny) Patent Number: 6,043,231 Date filed: August 31, 1993 Abstract: A method for treating mammals suffering from conditions associated with excess phospholipase A.sub.2 activity and/or production comprising administering to the mammal an effective amount of a non-antimicrobial tetracycline sufficient to inhibit excess phospholipase A.sub.2 activity and/or production is disclosed. A pharmaceutical composition is also disclosed.
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Excerpt(s): The present invention relates to a method of treating mammals suffering from conditions associated with excessive phospholipase A.sub.2 activity and/or production by administering to the mammal an amount and/or a type of a tetracycline that is not effectively antimicrobial but which effectively inhibits excessive phospholipase A.sub.2 activity and/or production. Excessive phospholipase A.sub.2 activity and/or production has been implicated in several disease conditions including; rheumatoid arthritis and other tissue destructive conditions, sepsis, septic shock, multisystem organ failure, pancreatitis, malaria, psoriasis and inflammatory bowel diseases. A composition useful in the treatment of mammals suffering from conditions associated with excessive phospholipase A.sub.2 activity and/or production is provided as well. Phospholipase A.sub.2 (PLA.sub.2) is a ubiquitous lipolytic enzyme that has been implicated as a possible mediator of inflammation. Pruzanski et al., Immuno. Today 12: 143-146 (1991). Specifically, PLA.sub.2 hydrolyses the 2-acyl position of glycerophospholipids, liberating free-fatty acids, mainly arachidonic acid and lysophosphatides. Granstrom, Inflammation 8: S15-25 (1984, suppl 5), O'Flaherty, Lab. Invest. 47: 314-329 (1982). Subsequently, it is believed that arachidonic acid is converted into a variety of proinflammatory eicosanoids. Trang, Semm. Arthritis Rheum. 9: 153190 (1980), Williams, Br. Med. Bull. 39: 239-242 (1983). As indicated above, one of the suggested mechanisms of inflammation involves the activation of the arachidonic acid cascade which results in the liberation of a variety of proinflammatory eicosanoids. Van den Bosch, Biochem. Biophys. Acta 604: 191-246 (1980), Vadas et al., Lab. Invest. 55: 391404 (1986). More recently, it has been suggested that PLA.sub.2 controls the first step in the liberation of arachidonic acid from phospholipids. Vadas et al., Lab. Invest. 55: 391404 (1986). It has also been suggested that the inflammatory process may be conceptualized as a four-stage event: 1) exposure to the injurious agent, 2) synthesis and release of proximal mediators, 3) synthesis and secretion of PLA.sub.2 and 4) synthesis and release of distal effectors. Pruzanski et al., Immuno. Today 12: 143-146 (1991). Web site: http://www.delphion.com/details?pn=US06043231__ •
Long-acting oxytetracycline composition Inventor(s): Holmes; Drew (Bryansford, GB), Patterson; Alan (Belfast, GB) Assignee(s): Norbrook Laboratories Limited (northern Ireland, Gb) Patent Number: 6,310,053 Date filed: July 17, 2000 Abstract: An injectable composition is described having a higher residual effect with reduced detrimental effects such as pain at injection site, swelling, tissue irritancy or necrosis. The composition contains as active principle a tetracycline compound, either as the free base or a salt thereof with a physiologically acceptable acid, complexed with a substantially equimolar amount of a magnesium compound, and is solubilized in a water miscible solvent system comprising glycerol formal in a an amount of about 40 (v/v); with from about 1% to about 20% (v/v) polyethylene glycol and optionally containing a pH modifier in an amount sufficient to maintain a physiologically acceptable pH. In addition, the composition may further comprise a thickener, such as polyvinyl in an amount of about 10% (w/v). The balance of the composition comprises water. Excerpt(s): This invention relates to injectable formulations containing tetracycline, particularly oxytetracycline, which exhibit higher residual effect with less of the known detrimental effects such as pain at injection site, swelling, tissue irritancy or necrosis.
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Preparation of pharmaceutical compositions containing tetracycline, and oxytetracycline in particular, has always presented a challenge due to aqueous solubility constraints which firstly have impact upon composition stability, and secondly upon parenteral administration. Prior art oxytetracycline compositions have exhibited relatively high viscosity at low temperatures which makes injection difficult, have shown poor stability and suffered limitations on strength of active principle. Thus, considerable research has gone into determining suitable complexing agents and more favorable co-solvents to address these shortcomings. A review of the art suggests that presence of calcium, and especially magnesium the formulation now appears mandatory as a complexing agent and whereas some improvements have been made in stability and delivery by adopting various co-solvent systems, higher concentration loadings and residual effects remain areas in which improvements are needed. This is especially of interest for veterinary purposes where the need is to deliver high effective doses with minimum effort in animal handling and detrimental effect on the animals requiring treatment. Web site: http://www.delphion.com/details?pn=US06310053__ •
Method of inhibiting cancer growth Inventor(s): Block; Norman L. (19000 SW. 72nd Ave., Miami, FL 33156), Golub; Lorne M. (29 Whitney Gate, Smithtown, NY 11787), Lee; Hsi-Ming (20 Allyson Pl., Setauket, NY 11733), Lokeshwar; Balakrishna L. (12615 SW. 112 Ct., Miami, FL 33176), McNamara; Thomas F. (Box 44, Port Jefferson, NY 11777), Ramamurthy; Nungavaram S. (10 Lynam Ct., Smithtown, NY 11787), Selzer; Marie G. (6035 Bayview Dr., Fort Lauderdale, FL 33308), Simon; Sanford (71 Cedar St., Stony Brook, NY 11790) Assignee(s): None Reported Patent Number: 6,100,248 Date filed: January 15, 1998 Abstract: The invention is a method of inhibiting cancer growth, by inhibiting cellular proliferation, invasiveness, or metastasis, or by inducing cytotoxicity against cancer in mammals. The method employs 6-demethyl-6-deoxy-4-de(dimethylamino)tetracycline (CMT-3) and other functionally related chemically modified, preferably nonantibacterial, tetracycline compounds to inhibit cancer growth. The method is particularly effective to inhibit the establishment, growth, and metastasis of solid tumors, such as tumors derived from colon cancer cells, breast cancer cells, melanoma cells, prostatic carcinoma cells, or lung cancer cells. Excerpt(s): The invention relates to methods of reducing cancer growth in biological systems. More specifically, the invention relates to the inhibition of solid tumor invasiveness and metastasis in mammals. Cancer, in all of its myriad manifestations, remains a devastating scourge upon mankind. While progress in preventing and treating cancer has been made, including particular success against Hodgkin's lymphoma and certain other forms, many types of cancer remain substantially impervious to prevailing treatment protocols. Typically, cancer is treated by chemotherapy, in which highly toxic chemicals are given to the patient, or by radiotherapy, in which toxic doses of radiation are directed at the patient. While commonly effective to kill huge numbers of cancer cells, these "cytotoxic" treatments also kill extraordinary numbers of healthy cells, causing the patient to experience acute debilitating symptoms including nausea, diarrhea, hypersensitivity to light, hair loss, etc. The side effects of these cytotoxic compounds limits the frequency and dosage at
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which they can be administered. Such disabling side effects can be mitigated to some degree by using compounds that selectively target cycling cells, i.e., interfering with DNA replication or other growth processes in cells that are actively reproducing. Since cancer cells are characterized by their extraordinary ability to proliferate, such protocols preferentially kill a larger proportion of cancer cells in comparison to healthy cells, but cytotoxicity and ancillary sickness remains a problem. Other more recent developments include efforts to develop monoclonal antibodies specific for oncogenes or HLA specificities, to identify cancer cells with great precision. However, these procedures are very expensive and extremely procedurally elaborate, yet still fail to produce the desired efficacy. Indeed, such procedures have been reported to be effective in only a small subpopulation of treated patients. Web site: http://www.delphion.com/details?pn=US06100248__ •
Method of using tetracycline compounds to enhance interleukin-10 production Inventor(s): Golub; Lorne M. (Smithtown, NY), Greenwald; Robert A. (Melville, NY), Haas-Smith; Sally (Penfield, NY), Lee; Hsi-Ming (Setauket, NY), Moak; Susan A. (Bayside, NY), Ritchlin; Christopher T. (Canandaigua, NY) Assignee(s): The Research Foundation of State University of New York (albany, Ny), University of Rochester (rochester, Ny) Patent Number: 6,015,804 Date filed: September 11, 1998 Abstract: The invention is a method of enhancing endogenous interleukin-10 production in mammalian cells and tissues, which includes administering an effective amount of a tetracycline derivative. The method also includes enhancing interleukin-10 production by administering an effective amount of the tetracycline derivative to a mammal. Preferred tetracycline compounds are tetracycline compounds which have been modified to reduce or eliminate their antimicrobial activity. The method can be used to treat medical conditions in mammals characterized by excessive IL-1 and TNF.alpha. production. Excerpt(s): The present invention relates to a method of enhancing endogenous interleukin-10 (hereinafter IL-10) production in mammalian cells or tissues. Interleukins, interferons, colony stimulating factors and TNF.alpha. are examples of a group of diverse multi-functional proteins called cytokines. Cytokines are a class of secreted soluble proteins normally present in very low concentration in a variety of cells. Lymphoid, inflammatory hemopoietic and other cells such as connective tissue cells (e.g. fibroblasts, osteoblasts) secrete a variety of cytokines which regulate the immune, inflammatory, repair and acute phase responses by controlling cell proliferation, differentiation and effector functions. The effects of cytokines are mediated through binding to high affinity receptors on specific cell types. Collier et al., Trends in Pharmacol. Sci. 10: 427-431 (1989). For example, the cytokine interleukin-1 (IL-1) is produced in cell types such as macrophages, synoviocytes, Iceratinocytes, chondrocytes and polymorphonuclear leukocytes. It is known to play a role in numerous conditions, in particular conditions accompanied by inflammation. Web site: http://www.delphion.com/details?pn=US06015804__
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Methods and compositions for topical treatment of eye surface inflammation and related dry eye disease Inventor(s): Gilbard; Jeffrey P. (Weston, MA) Assignee(s): Advanced Vision Research (woburn, Ma) Patent Number: 6,432,934 Date filed: August 6, 1998 Abstract: Ophthalmic compositions and methods of using the same to simultaneously treat eye surface inflammation and dry eye are disclosed. The ophthalmic preparation contains a tetracycline compound in aqueous solution. The preparation preferably further includes a balance of electrolytes sufficient to maintain or restore essentially normal levels of conjunctival mucus-containing goblet cells and corneal glycogen. These electrolytes can include potassium, chloride, bicarbonate, sodium, calcium, magnesium and phosphate. Excerpt(s): This invention relates to therapeutic ophthalmic preparations and methods of using the preparations locally to treat eye surface inflammation including meibomianitis and related dry eye disease. More particularly, it relates to topical ophthalmic solutions containing tetracycline compounds to suppress eye surface inflammation, including meibomianitis, while maintaining or restoring conjunctival mucus-containing goblet cells. Systemic tetracyclines are currently used to treat ocular rosacea, a condition characterized by eye surface inflammation, and a variety of related eye disorders such as blepharitis, meibomianitis, keratitits, conjunctival hyperemia, and eyelid hyperemia. Open-label prospective studies have been published describing a decrease in blepharitis and conjunctival hyperemia associated with ocular rosacea following systemic administration of tetracycline (1, 2). Systemic oxytetracycline treatment of ocular rosacea has also been tested in a double-masked trial and found to be more effective than placebo in inducing remissions (3). In the trial, it was reported that eyelid and conjunctival hyperemia responded well, as did the associated blepharitis. Based on these studies and clinical experience, oral tetracyclines has been recommended for treating meibomianitis, blepharitis and eye surface inflammation (4, 5, 6). Meibomianitis is a disorder characterized by inflammation centered about the meibomian glands. When inflammation includes most of the eye lid, the general term "blepharitis" may be applied. When inflammation includes the conjunctiva, the term "conjunctivitis" applies. When inflammation involves the cornea, the term "keratitis" applies. The eye surface includes the eye lids, cornea and conjunctiva. Recently, it was observed that meibomianitis and eye surface inflammation develops in a rabbit model for meibomian gland dysfunction (7). Analogous findings have been reported in humans (8, 9). These studies show that meibomianitis leads to meibomian gland dysfunction, with loss of meibomian gland oil from the tear film, an increase in tear film evaporation, a loss of water from the tear film and the development of dry eye surface disease. Web site: http://www.delphion.com/details?pn=US06432934__
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Methods and compositions for treatment of inflammatory disease Inventor(s): Levin; Bruce (One Independence Place, Philadelphia, PA 19106) Assignee(s): Levin; Bruce (philadelphia, Pa) Patent Number: 6,677,321 Date filed: November 28, 2000 Abstract: Compositions useful for treating inflammatory diseases including arthritis are disclosed which comprise cetyl myristoleate compounds or related compounds and at least one compound useful for treatment of inflammatory disease, such as tetracycline compounds, Cox-2 inhibitors, non-steroidal anti-inflammatory drugs (NSAIDs), corticosteroids, local anaesthetics, chelating agents, matrix metalloprotease inhibitors, inhibitors of inflammatory cytokines, glucosamine, chondroitin sulfate and collagen hydrolysate. Also disclosed are pharmaceutical compositions and methods of treatment for inflammatory disease and local inflammation and dermal irritation. Also disclosed are compositions including tetracycline and at least one compound useful for treatment of inflammatory disease. Excerpt(s): The present invention provides compositions and methods for prevention and treatment of arthritis and other inflammatory and autoimmune diseases. The present invention relates to a method for treating inflammatory disease to prevent or delay the progression of the disease process or to alleviate the symptoms thereof. Diseases and disorders which have significant inflammatory components are ubiquitous. Skin disorders, bowel disorders, certain degenerative neurological disorders, arthritis, autoimmune diseases and other illnesses afflict many patients. In certain disorders, infectious agents may be directly or indirectly responsible for the entire disease process. In other disorders, an infectious or other agent may in some way facilitate an autoimmune or inflammatory response. For many patients, dietary or environmental factors may trigger an autoimmune or inflammatory response. In many patients genetic factors can play a key role. In the majority of cases, the causative elements have not been defined and many of the key pathophysiological components have not been elucidated. Accordingly, treatment options for the majority of these diseases is suboptimal. Currently, steroids, nonsteroidal anti-inflammatory agents (NSAIDs), aspirin compounds and cancer chemotherapeutic immunosuppressive agents are often used. These agents often do not provide adequate symptomatic relief and are not believed to alter the natural progression of the disease. Indeed, some of these agents may make the disease worse. Furthermore, powerful side effects are found with most all of these therapies. Hence, there is a great need for safe and effective therapy for these disorders. Web site: http://www.delphion.com/details?pn=US06677321__
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Potent genetic switch allowing regulated gene expression in eukaryotic cells Inventor(s): Chatellard; Philippe (Lausanne, CH), Imhof; Markus O. (Ecublens, CH), Mermod; Nicolas (Buchillon, CH) Assignee(s): University of Lausanne (lausanne, Ch) Patent Number: 6,340,741 Date filed: August 9, 1999
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Abstract: The present invention provides a system for controlled transgene transcription using chimeric activator and repressor proteins functioning in a novel regulatory network. The target transgene is actively silenced in non-inducing conditions by a novel class of chimeric proteins consisting of the DNA-binding tetracycline repressor fused to distinct multimerized eukaryotic transcriptional repression domains. In the presence of a tetracycline "inducer", the repressor does not bind to the promoters for both the target gene and for another regulatory gene encoding a transactivator (e.g., GAL4-VP16). Under these inducing conditions, the transactivator activates expression of the target transgene and of its own gene, in an additional autoregulatory positive feedback loop. Excerpt(s): The present invention relates to the regulation of gene expression in eukaryotic cells. More specifically, the present invention relates to a system for controlled transgene transcription using both chimeric activator and repressor proteins. Expression of target genes with homo- and heterologous eukaryotic systems is widely used in biological and medical research, as well as biotechnology and somatic gene therapy. Recently, considerable progress has been made in the control of expression of target genes. Regulated gene expression has been achieved by the use of heterologous or artificial (chimerical) transcription factors responding to an exogenously added inducer drug which acts as a bona fide ligand. Typically, these transcription factors recognize cognate regulatory elements in the promoter of the target gene and the ligand regulates the interaction of the factor with the DNA or the interaction of the DNA-bound factor with a transcriptional activation domain. Ideally, the administration or removal of the ligand results in a switch between the on or off states of activity of the target gene. Several small molecule ligands have been shown to mediate regulated gene expressions, either in tissue culture cells and/or in transgenic animal models. These include the FK1012 and rapamycin immunosupressive drugs [Spencer et al., Science 262: 1019-1024 (1993); Magari et al., J. Clin. Invest. 100: 2865-2872 (1997)], the progesterone antagonist mifepristone (RU486) [Wang, Proc. Natl. Acad. Sci. USA 93: 8180-8184 (1994); Wang et al., Nature Biotech 15: 239-243 (1997)], the tetracycline antibiotic derivatives [Gossen and Bujard, Proc. Natl. Acad. Sci USA 89: 5547-5551 (1992); Gossen et al., Science 268: 1766-1769 (1995); Kistner et al., Proc. Natl. Acad. Sci. 93: 10933-10938 (1996)], and the insect steroid hormone ecdysone [No et al., Proc. Natl. Acad. Sci USA 93: 3346-3351 (1996)]. Web site: http://www.delphion.com/details?pn=US06340741__ •
pREM: a positive selection vector system for direct PCR cloning Inventor(s): Husain; Zaheed (Medford, MA), Malo; Madhu Sudan (Watertown, MA) Assignee(s): Synthegen Systems (medford, Ma) Patent Number: 6,544,782 Date filed: November 13, 2000 Abstract: The present invention describes the development of a positive selection vector based on regulatory element modulation, wherein such modulation is achieved via insertional reconstruction or destruction of a regulatory element controlling transcription, translation, DNA replication and termination. A positive selection cloning vector pREM5Tc has been developed based on insertional reconstruction of a regulatory element of a reporter gene. The vector pREM5Tc carries the tetracycline resistance reporter gene with no functional -35 region of its promoter, a regulatory element, thus resulting in no expression of the tetracycline resistance gene. Hence a host cell carrying the vector pREM5Tc is unable to produce the tetracycline resistance gene protein
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resulting in inhibition of its growth in presence of tetracycline. An E. coli consensus -35 region is recognized as 5'-TTGACA-3' and a primer used in polymerase chain reaction (PCR) carries at its 5' end the sequence 5'-TGTCAA-3', which is the complementary sequence of 5'-TTGACA-3'. The PCR-amplified DNA fragment is ligated to pREM5Tc thus reconstructing the functional promoter of the tetracycline resistance reporter gene. Subsequent transformation of a host cell with the recombinant vector (carrying an insert DNA) results in production of the tetracycline resistance reporter gene protein that confers resistance to tetracycline thus allowing only the recombinants to grow in presence of tetracycline. The positive selection vector pREM5Tc greatly reduces, if not eliminates, the number of exonuclease-generated false positive clones. Excerpt(s): Ahrenhotz et al., "A conditional suicide system in Escherichia coli based on intracellular degradation of DNA" Appl. Environ. Microbiol. 60,3746-3751(1994). Altenbuchner et al., "Positive selection vectors based on palindromic DNA sequences" Methods Enzymol. 216, 457-466 (1992). Balbas et al., "Plasmid vector pBR322 and its special-purpose derivatives--a review" Gene 50, 3-40 (1986). Web site: http://www.delphion.com/details?pn=US06544782__ •
Recombinant.beta.-cell and uses thereof Inventor(s): Efrat; Shimon (Bronx, NY) Assignee(s): Albert Einstein College of Medicine of Yeshiva University (bronx, Ny) Patent Number: 6,114,599 Date filed: March 19, 1998 Abstract: The present invention provides a recombinant, glucose-regulated insulin producing beta cell whose proliferation is controlled by tetracycline or a derivative thereof. The present invention also provides a method for treating a subject with diabetes using the recombinant beta cell of the present invention. Excerpt(s): Diabetes mellitus is a chronic disorder of carbohydrate metabolism characterized by insufficient production of insulin by the pancreatic beta cells. Diabetes effects approximately 10 million people in the United States, with more than 250,000 new cases diagnosed each year. There are two common types of diabetes mellitus: insulin-dependent (Type-I diabetes) and non-insulin-dependent (Type-II diabetes). Insulin-dependent diabetes is generally characterized by an absolute deficiency of insulin production, whereas non-insulin-dependent diabetes is characterized by a relatively insufficient production of insulin. In normal individuals, the rate of insulin secretion by beta cells is regulated by the level of glucose in the blood. When the blood glucose level rises, the islet cells are stimulated to release increased amounts of insulin into the blood, accelerating glucose transport into the cells and glucose conversion into glycogen. As the blood glucose level falls, insulin release from the islets is decreased. In the diabetic subject, insulin production is abnormally low or insufficient, resulting in abnormally high blood glucose levels, a condition known as hyperglycemia. In addition to diet and exercise programs, the constant and life long monitoring of blood glucose levels in conjunction with injections of insulin is central to the current methods for the treatment of the insulin-dependent diabetic subject. Many diabetic subjects, however, have difficulty in controlling their blood glucose levels using the current treatment methods, thus constantly exposing themselves to the adverse effects of hypoglycemia (abnormally low blood glucose levels) and hyperglycemia. Web site: http://www.delphion.com/details?pn=US06114599__
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Retardation of metalloproteinase incidental to HIV and/or AIDS Inventor(s): Berman; Charles L. (211 Central Park West, New York, NY 10024) Assignee(s): None Reported Patent Number: 6,063,775 Date filed: April 29, 1997 Abstract: The instant invention provides a product of manufacture for retarding the biochemical formation of metalloproteinase, including gelatinase, elastase, collaginase, and the like, within the tissues of the body of a patient who has been inflicted with the HIV virus and/or the HIV virus which has advance to the AIDS virus, through the administration of an effective amount of a non-antimicrobial/non-antibiotic/nonantibacterial, chemically modified tetracycline (CMT) analog, its salts, cojugates and/or derivatives, and combinations thereof. Excerpt(s): The instant invention broadly relates to retardation of the biochemical formation of materials incidental to HIV and/or AIDS, which promote the advancement of HIV to AIDS; which promote the advancement of AIDS and other opportunistic diseases to which a patient could inevitably succumb. Specifically, the invention retards the biochemical formation of species of metalloproteinase which are formed as a product of conditions such HIV and/or AIDS. Still more specifically, the invention provides for the administration of an effective amount of a drug which retards the biochemical formation of metalloproteinase species including coliagenase and gelatinase, incidental to the conditions of HIV and/or AIDS. Still even more specifically, the invention provides for the administration of an effective amount of a chemically modified tetracycline (CMT) analog which retards the biochemical formation of metalloproteinase species including gelatinase, collagenase and elastase, incidental to the conditions of HIV and/or AIDS. Tetracyclines are useful as broad spectrum antibiotics because they have the ability to retard protein synthesis in a wide variety of bacteria. As disclosed in the above-identified pending patent applications, it has also been discovered that tetracyclines, antibiotic tetracyclines and non-antibiotic tetracyclines, have the ability to retard collagen-destructive enzymes, such as collagenase, responsible for the breakdown of connective tissue in a number of diseases, such as periodontal disease, corneal ulcers and rheumatoid arthritis. The use of tetracycline antibiotics, while effective, may lead to undesirable side effects. For example, the long term administration of antibiotic tetracyclines may reduce or eliminate healthy flora, such as intestinal flora, and may lead to the production of antibiotic resistant organisms or the overgrowth of yeast and fungi. Web site: http://www.delphion.com/details?pn=US06063775__
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Systemic and/or local (topical) application of tetracycline and/or tetracycline derivative(s) for treating, suppressing and preventing of cerebrovascular diseases, traumas and damages of nervous system Inventor(s): Kaikkonen; Auvo (Tampere, FI), Keinanen; Riitta (Kuopio, FI), Koistinaho; Jari (Vuorela, FI), Miettinen; Susanna (Kuopio, FI), Tormala; Pertti (Tampere, FI), Vartiainen; Nina (Jamsa, FI), Yrjanheikki; Juha (Ylitornio, FI) Assignee(s): Bioabsorbable Concepts, Inc. (tampere, Fi) Patent Number: 6,277,393 Date filed: December 10, 1999
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Abstract: A method for treating and/or preventing of cerebrovascular diseases, traumas and damages of the nervous system, which method includes local (topical) and/or systemic application of an effective amount of tetracycline and/or tetracycline derivative or a mixture of tetracycline and/or tetracycline derivative(s) ("active agent(s)"), optionally in a pharmaceutically-acceptable diluent, carrier or release system ("active compostition"). Excerpt(s): This invention is in the area of the treatment and/or preventing of cerebrovascular diseases, traumas and damages of the nervous system ("neural injuries"), and includes local (topical) or systemic application of an effective amount of tetracycline, tetracycline derivative or a mixture of tetracycline and/or tetracycline derivative(s) ("active agent(s)"), optionally in a pharmaceutically-acceptable diluent, carrier or tetracycline release system ("active composition"). Degeneration, traumas and injuries of the nervous system, comprising brain, spinal cord and peripheral nerves, are characteristic of certain diseases and common consequences of accidents. Cerebrovascular accident (CVA) is a clinical definition used to describe symptoms of an acute neurological disorder caused by disturbance of the cerebral blood supply. Intracerebral and subarachnoid hemorrhages account for approx 20% of CVAs and 80% are of ischemic type. Stroke defines all conditions in which the duration of the CVA symptoms exceeds 24 h. Hemorrhagic strokes may be situated intra- or extracerebrally. Intracerebral hemorrhage can be caused by artery aneurysm rupture, and a subdural hemorrhage by cranial trauma. See, Ter Horst G J and Postigo A., In: Ter Horst G J and Korf J (eds.), ClinicalPharmacology of Cerebral Ischemia, Humana Press, Totowa, N.J., 1-30, 1997, the entire disclosure of which is incorporated herein by reference. The causes of ischemic stroke are numerous and include large artery atherosclerosis, small vessel occlusion, embolisms, and thrombosis. Focal (regional) ischemia is clinically more common than global (forebrain) ischemia A focal insult usually occurs after thrombosis or embolus in the middle cerebral artery, whereas global ischemia results from transient cardiac arrest. See, Ter Horst G J and Postigo A., In: Ter Horst G J and Korf J (eds.), Clinical Pharmacology of Cerebral Ischemia, Humana Press, Totowa, N.J., 1-30, 1997. Web site: http://www.delphion.com/details?pn=US06277393__ •
Tetracycline derivatives Inventor(s): Vu; Chi Bao (Chestnut Hill, MA) Assignee(s): Pfizer Inc (new York, Ny) Patent Number: 6,165,999 Date filed: February 23, 1998 Abstract: The present invention relates to novel tetracycline derivatives, to intermediates used in their preparation, to pharmaceutical compositions containing them and to their medicinal use. Excerpt(s): The present invention relates to novel tetracycline derivatives to intermediates used in their preparation, to pharmaceutical compositions containing them and to their medicinal use. European Patent Publication 618,120, published Oct. 5, 1994, refers to 9-[(substituted glycyl)amido]-6-(substituted)-5-hydroxy-6deoxytetracyclines, methods for their production and methods of using the active agents for the prevention, treatment or control of bacterial infections in warm-bloooded animals. European Patent Publication 536,515, published Apr. 14, 1993, refers to 7substituted-9-(substituted amino)-6-demethyl-6-deoxytetracyclines, methods for their
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production and methods of using the active agents for the prevention, treatment or control of bacterial infections in warm-blooded animals. Web site: http://www.delphion.com/details?pn=US06165999__ •
Tetracycline repressor regulated mammalian cell transcription and viral replication switch Inventor(s): Yao; Feng (Newton Center, MA) Assignee(s): Brigham and Women's Hospital (boston, Ma) Patent Number: 6,251,640 Date filed: April 21, 1999 Abstract: The present invention is directed to DNA constructs suitable for gene expression in mammalian cells and which are characterized by the presence of a mammalian promoter under the control of a tet operator/repressor system. The DNA may be used as part of a system for expressing recombinant protein. In addition, the tet operator/repressor system can be used to engineer cis- and trans-destructive viruses which are capable of replicating in the presence of the tet repressor, but not in the absence of the repressor. These viruses can be used either directly in the treatment of patients with corresponding viral diseases, as vehicles for the delivery of nucleic acids that can serve as therapeutic agents and as part of vaccines designed to immunize people or animals against viral diseases. Excerpt(s): The present invention is concerned with compositions and methods that rely upon the tetraycline resistance (tet) operator and repressor to control transcription in mammalian cells. It encompasses methods for recombinantly producing proteins and the vectors and host cells utilized in such methods. In addition, the present invention is directed to viruses which are recombinantly engineered so that their replication is controlled by the tet operator/repressor system. These viruses may serve as vehicles for gene transfer both in vitro and in vivo; as agents for immunization; and as a means for delivering nucleic acid therapeutic agents to cells. The ability to specifically regulate transgene expression has been a central concern in molecular biology for many years. In the case of mammalian cells, the in vitro regulation of recombinant genes has most often been accomplished through the use of inducible promoters that respond to agents such as heavy metal ions (Brinster, et al., Nature 296:39-42 (1982); heat shock (Nover, in Heat Shock Response, pp. 167-220, CRC, Fla. (1991)); and hormones (Klock, et al., Nature 329:734-736 (1987)). Unfortunately, these promoters generally provide only a relatively a low level of expression even in the presence of inducer and most of the inducers that have been used in vitro have unacceptable side effects in vivo. As an alternative to inducible promoters, attempts have been made to control mammalian gene expression using well-characterized prokaryotic regulatory elements. In most cases, regulatory systems have relied upon strong interactions between prokaryotic operators and repressor proteins as a means for either targeting eukaryotic transcription modulators to specific sites within a host cell genome (see e.g., Labow, et al., Mol. Cell. Biol. 10:33433356 (1990)) or in attempts to directly inhibit gene expression using the prokaryotic repressor (see e.g., Brown, et al., Cell 49:603-612 (1987)). Web site: http://www.delphion.com/details?pn=US06251640__
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Transgenic organisms having tetracycline-regulated transcriptional regulatory systems Inventor(s): Bujard; Hermann (Heidelberg, DE), Gossen; Manfred (El Cerrito, CA) Assignee(s): Basf Aktiengesellschaft (de), Knoll Aktiengesekkscgaft (de) Patent Number: 6,242,667 Date filed: September 28, 1998 Abstract: Transgenic animals carrying a transgene comprising a nucleic acid molecule encoding protein useful for regulating the expression of genes in eukaryotic cells and organisms in a highly controlled manner are disclosed. In the regulatory system of the invention, transcription of a tet operator-linked nucleotide sequence is stimulated by a transcriptional activator fusion protein composed of two polypeptides, a first polypeptide which binds to tet operator sequences in the presence of tetracycline operatively linked to a second polypeptide activates transcription in eukaryotic cells. In a preferred embodiment, the transgene encoding the transcriptional activator fusion protein is integrated at a predetermined location within the chromosome of the transgenic animal. Excerpt(s): Functional analysis of cellular proteins is greatly facilitated through changes in the expression level of the corresponding gene for subsequent analysis of the accompanying phenotype. For this approach, an inducible expression system controlled by an external stimulus is desirable. Ideally such a system would not only mediate an "on/off" status for gene expression but would also permit limited expression of a gene at a defined level. Attempts to control gene activity have been made using various inducible eukaryotic promoters, such as those responsive to heavy metal ions (Mayo et al. (1982) Cell 29:99-108; Brinster et al. (1982) Nature 296:39-42; Searle et al. (1985) Mol. Cell. Biol. 5:1480-1489), heat shock (Nouer et al. (1991) in Heat Shock Response, e.d. Nouer, L., CRC, Boca Raton, Fla., pp167-220) or hormones (Lee et al. (1981) Nature 294:228-232; Hynes et al. (1981) Proc. Natl. Acad. Sci. USA 78:2038-2042; Klock et al. (1987) Nature 329:734-736; Israel & Kaufman (1989) Nucl. Acids Res. 17:2589-2604). However, these systems have generally suffered from one or both of the following problems: (1) the inducer (e,g, heavy metal ions, heat shock or steroid hormones) evokes pleiotropic effects, which can complicate analyses, and (2) many promoter systems exhibit high levels of basal activity in the non-induced state, which prevents shut-off the regulated gene and results in modest induction factors. An approach to circumventing these limitations is to introduce regulatory elements from evolutionarily distant species such as E. coli into higher eukaryotic cells with the anticipation that effectors which modulate such regulatory circuits will be inert to eukaryotic cellular physiology and, consequently, will not elicit pleiotropic effects in eukaryotic cells. For example, the Lac repressor (lacR)/operator/inducer system of E. coli functions in eukaryotic cells and has been used to regulate gene expression by three different approaches: (1) prevention of transcription initiation by properly placed lac operators at promoter sites (Hu & Davidson (1987) Cell 48:555-566; Brown et al. (1987) Cell 49:603-612; Figge et al. (1988) Cell 52:713-722; Fuerst et al. (1989) Proc. Natl. Acad Sci. USA 86:2549-2553: Deuschle et al. (1989) Proc. Natl. Acad. Sci. USA 86:5400-5405); (2) blockage of transcribing RNA polymerase II during elongation by a LacR/operator complex (Deuschle et al. (1990) Science 248:480-483); and (3) activation of a promoter responsive to a fusion between LacR and the activation domain of herpes simples virus (HSV) virion protein 16 (VP16) (Labow et al. (1990) Mol. Cell. Biol. 10:3343-3356; Baim et al. (1991) Proc. Natl. Acad. Sci. USA 88:5072-5076).
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Web site: http://www.delphion.com/details?pn=US06242667__ •
Transgenic organisms having tetracycline-regulated transcriptional regulatory systems Inventor(s): Bujard; Hermann (Heidelberg, DE), Gossen; Manfred (El Cerrito, CA), Salfeld; Jochen G. (North Grafton, MA), Voss; Jeffrey W. (West Boylston, MA) Assignee(s): Basf Aktiengesellschaft (de), Knoll Aktiengesellschaft (de) Patent Number: 6,252,136 Date filed: September 29, 1998 Abstract: Transgenic animals carrying two transgenes, the first coding for a transactivator fusion protein comprising a tet repressor and a polypeptide which directly or indirectly activates in eucaryotic cells, and the second comprising a gene operably linked to a minimal promoter operably linked to at least one tet operator sequence, are disclosed. Isolated DNA molecules (e.g., targeting vectors) for integrating a polynucleotide sequence encoding a transactivator of the invention at a predetermined location within a second target DNA molecule by homologous recombination are also disclosed. Transgenic animals having the DNA molecules of the invention integrated at a predetermined location in a chromosome by homologous recombination are also encompassed by the invention. Methods to regulate the expression of a tet operator linked-gene of interest by administering tetracycline or a tetracycline analogue to an animal of the invention are also disclosed. The regulatory system of the invention allows for conditional inactivation or modulation of expression of a gene of interest in a host cell or animal. Excerpt(s): The study of gene function in complex genetic environments such as eucaryotic cells would greatly profit from systems that would allow stringent control of the expression of individual genes. Ideally, such systems would not only mediate an "on/off" status for gene expression but would also permit limited expression at a defined level. Attempts to control gene activity by various inducible eucaryotic promoters responsive to, for example, heavy metal ions (Mayo et al., Cell 29:99-108 (1982); Brinster et al., Nature (London) 296:39-42 (1982); Searle et al., Nouer, L., CRC Boca Raton, Fla. (1991), pp. 167-220), or hormones (Lee et al., Nature (London) 294:228232 (1981); Hynes et al., Proc. Natl. Acad. Sci. U.S.A. 78:2038-2042 (1981); Klock et al., Nature (London) 329:734-736 (1987); Israel & Kaufman, Nucleic Acids Res. 17:2589-2604 (1989)) have generally suffered from leakiness of the inactive state (e.g., the metallothionein promoter (Mayo et al., Cell 29:99-108 (1982)) or from pleiotropic effects caused by the inducing principles themselves, such as elevated temperature or glucocorticoid hormone action (Lee et al., Proc. Natl. Acad. Sci, U.S.A. 85:1204-1208 (1988)). In search of regulatory systems that do not rely on endogenous control elements, several groups have demonstrated that the lac repressor/operator inducer system of Escherichia coli functions in eucaryotic cells. Three approaches have been described: (i) prevention of transcription initiation by properly placed lac operators at promoter sites (Hu & Davidson, Cell 48:555-566 (1987); Brown et al., Cell 49:603-612 (1987); Figge et al., Cell 52:713-722 (1988); Fuerst et al., Proc. Natl. Acad. Sci. U.S.A. 86:2549-2553 (1989); Deutschle et al., Proc. Natl. Acad. Sci. U.S.A. 86:5400-5405 (1989)), (ii) blockage of transcribing RNA polymerase II during elongation by a lac repressor/operator complex (lac R/O; Deutschle et al., Science 248:480-483 (1990)), and (iii) activation of a promoter responsive to a fusion between lacR and the activating domain of virion protein 16 (VP16) of herpes simplex virus (HSV) (Labow et al., Mol.
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Cell. Biol. 10:3343-3356 (1990); Baim et al., Proc. Natl. Acad. Sci. U.S.A. 88:5072-5076 (1991)). Web site: http://www.delphion.com/details?pn=US06252136__ •
Treatment of diseases of the eye characterized by the formation of metalloproteinase Inventor(s): Berman; Charles L. (211 Central Park West, New York, NY 10024) Assignee(s): None Reported Patent Number: 6,384,081 Date filed: October 9, 1998 Abstract: The instant invention provides a method of inhibiting the formation of metalloproteinase and its species, within the eyes of a patient inflicted with at least one form of retinitis characterized by the presence of metalloproteinase, through the administration of an effective dosage that includes an a tetracycline analog, its salts, conjugates or derivatives. In an alternate preferred embodiment of the invention, the dosage includes at least one other therapeutic substance in effective combination with a tetracyline analog. Excerpt(s): The instant invention broadly relates to inhibition of the formation of substances which promote the advancement of diseases that can cause blindness, More specifically, the invention inhibits the formation of species of metalloproteinase which are formed as a product of diseases of the eye. Still more specifically, in a preferred embodiment, the invention provides for the administration of an effective amount of a tetracycline analog, its salts, conjugates or derivatives for inhibiting the formation of metalloproteinase species including collagenase, elastase, and most particularly, geletanase in various parts of the eye, more particularly, the retina and/or vitreous of a patient inflicted with an advancing eye disease, most particularly, at least one of any form of retinitis characterized by the formation of metalloproteinase and its species. In an alternate preferred embodiment, the invention provides for the administration of an effective amount of a tetracycline analog, its salts, conjugates or derivatives, in synergistic combination with at least one other therapeutic substance, its salts, conjugates or derivatives, for inhibiting the formation of metalloproteinase species including collagenase, elastase, and most particularly, geletanase in various parts of the eye, more particularly, the retina and/or vitreous of a patient inflicted with an advancing eye disease, most particularly, at least one of any form of retinitis characterized by the formation of metalloproteinase and its species. Mammalian extracellular matrix (ECM) turnover is thought to be initiated by the secretion of several proteinases, which cause partial degradation of specific matrix components. Thereafter, the disrupted matrix components are taken up and degraded further within lysosomal vesicles. Interstitial collagenase, gelatinase or type IV collagenase, and stromelysin or proteoglycanase are members of a family of matrix metalloproteinases with sufficient diversity in substrate specificities to achieve this initial disruption. These metalloproteinases are active at neutral pH and are known to be secreted by a variety of different cell types. Interstitial collagenase (MMP-1), also called type I-II-III collagenase is an endopeptidase capable of cleaving each of the.alpha.-chains of the collagen triple helix at a Gly-Ile or Gly-Leu site located about one-fourth the distance from the carboxyterminus. This produces thermally unstable soluble fragments about one-fourth and three-fourths the original size, which in turn are susceptible to degradation by gelatinases. Hasty et al., J. Biol. Chem. 262, 10048-10052 (1987) report by immunologically distinct interstitial collagenases from fibroblasts and neutrophils. The
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latter has a higher catalytic rate toward Type I collagen, while the former is more active toward Type III collagen. Goldberg et al., J. Biol. Chem. 261, 6600-6605 (1986) report that there are two forms of interstitial collagenase produced by human skin fibroblasts-one, an unmodified procollagenase, Mr.apprxeq.52 kDa, and the other, a glycosidated form, Mr.apprxeq.57 kDa. None of these interstitial collagenases appear capable of degrading Type IV or V collagen. Web site: http://www.delphion.com/details?pn=US06384081__ •
Use of anabolic agents anti-catabolic agents and antioxidant agents for protection treatment and repair of connective tissues in humans and animals Inventor(s): Corson; Barbara E. (Fawn Grove, PA), Hammad; Tarek (Baltimore, MD), Henderson; Todd R. (Jarrettsville, MD), Lippiello; Louis (Scottsdale, AZ), Soliman; Medhat (Minya, EG) Assignee(s): Nutramax Laboratories, Inc. (edgewood, Md) Patent Number: 6,451,771 Date filed: February 12, 1999 Abstract: The present invention relates to compositions for the protection, treatment and repair of connective tissues in humans and animals comprising any or all of anabolic, anti-catabolic, and anti-oxidant agents, including aminosugars, S-adenosylmethionine, arachadonic acid, GAGs, pentosan, collagen type II, tetracyclines or tetracycline-like compounds, diacerin, super oxide dismutase, and L-ergothionine and to methods of treating humans and animals by administration of these novel compositions to humans and animals in need thereof. Excerpt(s): The present invention relates to compositions for the protection, treatment and repair of connective tissues in humans and animals. The tissues of mammals, including humans, are in a constant state of flux between the anabolic processes that build up tissues, and the catabolic processes which degrade tissues. The state of health exists when there is a balance between these two processes, and derangements of the balance produce disease. This holds true for all tissues of the body. Connective tissues are of particular importance for several reasons. First, they support the "functional cells" of the body, i.e., epithelial, muscle and neural cells. Second, they play critical roles in intercellular communication, which is essential for multicellular life. The inflammatory process occupies a key position in this balance. When injury to tissues occurs, inflammation initiates the biochemical processes that result in tissue repair. Because inflammation results in the symptoms of pain, inflammation, and swelling of the tissues involved, it is often regarded by both patients and physicians as an abnormal and undesirable state, which should be treated and relieved as soon and as completely as possible. As a result, pharmacies are full of "anti-inflammatory drugs" (such as corticosteroids and the non-steroidal anti-inflammatory drugs, such as aspirin). Under certain circumstances, inflammation can indeed be destructive; however, it is important to remember that inflammation is closely linked with tissue healing. Indeed, inflammation is not easily categorized as strictly anabolic or catabolic--it may have either effect. Its purpose in the body is to remove, dilute or wall-off the injurious agent(s). It also sets into motion the biochemical processes that repair and reconstruct the damaged tissue. Because it is essential to healing, and because it can also cause tissue destruction, inflammation and its mediators are important factors in the anabolic and catabolic balance.
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Use of tetracycline derivatives in treating multiple sclerosis Inventor(s): Duncan; Ian D. (Madison, WI), Zhang; Su-Chun (Madison, WI) Assignee(s): Wisconsin Alumni Research Foundation (madison, Wi) Patent Number: 6,613,756 Date filed: May 3, 2001 Abstract: A method of treating multiple sclerosis is disclosed. In one embodiment, the method comprises the step of treating a multiple sclerosis patient with a tetracycline derivative, wherein the multiple sclerosis symptoms of the patient are diminished. Excerpt(s): There is an urgent need for the development of new drugs or a new application of existing drugs to the treatment of multiple sclerosis and other incurable neurologic disorders. The application of tetracycline derivatives, such as minocycline or doxycycline, to the treatment of multiple sclerosis based on our data is an advance in the treatment of this disease, both as a primary therapy and in support of transplantinduced brain repair. Multiple sclerosis is an inflammatory disease of the central nervous system (CNS) in which demyelination results in a variety of neurologic deficits. In many patients the disease relapses and remits while in others there is a progressive worsening with no remissions. At present, the only drugs that have been found to be effective in slowing or lessening the disease burden are.beta.-interferon and copolymerI. However, neither cures the disease and in many patients there is little or no effect. While T-cells are the early inflammatory cells found in areas of demyelination (plaques) in multiple sclerosis patients, microglia in these areas become activated and are thought to produce a number of cytotoxic cytokines. These cytokines are then thought to play a key role in the subsequent demyelination and oligodendrocyte death. The best available model of multiple sclerosis is EAE (Experimental Allergic Encephalomyelitis). While there are differences between EAE and Multiple Sclerosis, EAE remains as the standard model in which to test therapeutic strategies. Indeed, some Phase I trials in multiple sclerosis patients have been based on experimental therapies of EAE. While EAE can be generated in both rats and mice and by using a number of protocols, we induce the disease in DA (Dark Agouti) rats by the injection of myelin-oligodendrocyte glycoprotein (MOG) in incomplete Freund's adjuvant. This creates a severe, often relapsing-remitting neurologic disease, like multiple sclerosis, with paralysis of the hind limbs 12-15 days after immunization. Histologically, there is scattered demyelination associated with inflammation and microglial activation. Web site: http://www.delphion.com/details?pn=US06613756__
Patent Applications on Tetracycline 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 tetracycline:
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This has been a common practice outside the United States prior to December 2000.
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7-Substituted fused ring tetracycline compounds Inventor(s): McIntyre, Laura; (Arlington, MA), Nelson, Mark L.; (Wellesley, MA) Correspondence: Lahive & Cockfield, LLP.; 28 State Street; Boston; MA; 02109; US Patent Application Number: 20040048835 Date filed: August 28, 2003 Abstract: 7-substituted fused ring tetracycline compounds, methods of treating tetracycline responsive states, and pharmaceutical compositions containing the 7substituted fused ring tetracycline compounds are described. Excerpt(s): This application is a continuation of U.S. patent application Ser. No. 09/852,908, filed May 10, 2001, Issuing, which claims priority to U.S. Provisional Patent Application Serial No.: 60/204,158, filed on May 15, 2000. The entire contents each of the aforementioned applications are hereby incorporated herein by reference. The development of the tetracycline antibiotics was the direct result of a systematic screening of soil specimens collected from many parts of the world for evidence of microorganisms capable of producing bacteriocidal and/or bacteriostatic compositions. The first of these novel compounds was introduced in 1948 under the name chlortetracycline. Two years later, oxytetracycline became available. The elucidation of the chemical structure of these compounds confirmed their similarity and furnished the analytical basis for the production of a third member of this group in 1952, tetracycline. A new family of tetracycline compounds, without the ring-attached methyl group present in earlier tetracyclines, was prepared in 1957 and became publicly available in 1967. Recently, research efforts have focused on developing new tetracycline antibiotic compositions effective under varying therapeutic conditions and routes of administration. New tetracycline analogues have also been investigated which may prove to be equal to or more effective than the originally introduced tetracycline compounds. Examples include U.S. Pat. Nos. 3,957,980; 3,674,859; 2,980,584; 2,990,331; 3,062,717; 3,557,280; 4,018,889; 4,024,272; 4,126,680; 3,454,697; and 3,165,531. These patents are representative of the range of pharmaceutically active tetracycline and tetracycline analogue compositions. Web site: http://appft1.uspto.gov/netahtml/PTO/search-bool.html
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ATTENUATED SALMONELLA STRAIN USED AS A VEHICLE FOR ORAL IMMUNIZATION Inventor(s): CHAKRABORTY, TRINAD; (BRAUNSCHWEIG, DE), DARJI, AYUB; (BRAUNSCHWEIG, DE), GERSTEL, BIRGIT; (BRAUNSCHWEIG, DE), GUZMAN, CARLOS A.; (BRAUNSCHWEIG, DE), TIMMIS, KENNETH; (BRAUNSCHWEIG, DE), WACHHOLZ, PETRA; (BRAUNSCHWEIG, DE), WEISS, SIEGFRIED; (BRAUNSCHWEIG, DE) Correspondence: Marshall O'toole Gerstein Murray; And Borun; 6300 Sears Tower; 233 South Wacker Drive; Chicago; IL; 606066402 Patent Application Number: 20030180320 Date filed: October 18, 1999 Abstract: An attenuated strain of Salmonella typhimurium has been used as a vehicle for oral genetic immunization. Eukaryotic expression vectors containing the genes for bgalactosidase, or truncated forms of ActA and listeriolysin--two virulence factors of
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Listeria monocytogenes--that were controlled by an eukaryotic promoter have been used to transform a S. typhimurium aroA strain. Multiple or even single immunizations with these transformants induced a strong cytotoxic and helper T cell response as well as an excellent antibody response. Multiple immunizations with listeriolysin transformants protected the mice completely against a lethal challenge of L. monocytogenes. Partial protection was already observed with a single dose. ActA appeared not to be a protective antigen.The strength and the kinetics of the response suggested that the heterologous antigens were expressed within the eukaryotic host cells following transfer of plasmid DNA from the bacterial carrier strain. Transfer of plasmid DNA could be unequivocally shown in vitro using primary peritoneal macrophages. The demonstration of RNA splice products and expression of.beta.galactosidase in the presence of tetracycline--an inhibitor of bacterial protein synthesis-indicated that the gene was expressed by host cells rather than bacteria. Oral genetic immunization with Salmonella carriers provides a highly versatile system for antigen delivery, represents a potent system to identify candidate protective antigens for vaccination, and will permit efficacious generation of antibodies against virtually any DNA segment encoding an open reading frame. Excerpt(s): This is a continuation-in-part of International Application No. PCT/EP97/06933 filed Dec. 11, 1997, the entire disclosure of which is incorporated herein by reference. The design of efficient vaccines against infectious diseases remains a major challenge in medical science. Low cost, non-invasive administration, life-long protection by single doses combined with ease of preparation, storage and transport are desirable goals to be achieved. In this respect, live attenuated bacterial carriers that express heterologous antigens are attractive vehicles for the oral delivery of vaccines. This type of delivery should result in a broad spectrum of both mucosal and systemic immune responses. Use of vaccine vectors overcomes some of the limitation of oral delivery of proteins, which usually need to be co-administered with adjuvant proteins such as cholera toxin to evoke an immune response (Brown et al., 1987; Flynn et al, 1990). In addition, administration of live replicating vectors might be advantageous over other forms of administration such as microencapsulation because of the immunomodulatory properties of cell wall components of bacteria. Finally, the natural route of entry could prove to be of benefit since many bacteria like Salmonella egress from the gut lumen via M cells into Peyer's Patches (Jones et al, 1994; Neutra et al, 1996; Siebers and Finley, 1996) and migrate eventually into lymph nodes and spleen, thus allowing targeting of vaccines to inductive sites of the immune system. Genetic immunization has recently provided a promising new approach to the vaccination problem (for review see Donnelly et al., 1997). Isolated plasmid DNA--introduced into muscle or skin of the host--leads to expression of antigen in the host cells when transcription is driven by eukaryotic control elements. This has led to B and T cell stimulation and to protective responses. How these responses are generated remains still unclear. Muscle cells apparently express low levels of MHC class I but lack MHC class II and costimulatory molecules. Although, it is not known which cells function as antigen presenting cells (APC) under these circumstances, it is likely that resident dendritic cells or macrophages capture the antigen and migrate to lymph nodes and spleen to stimulate CD4.sup.+ and CD8.sup.+ T cells. Indeed antigen expressing dendritic cells have been observed after genetic immunization into the skin using a gene gun (Condon et al., 1996). It is not known whether DNA is also transferred directly into dendritic cells when plasmids are applied into muscles. Web site: http://appft1.uspto.gov/netahtml/PTO/search-bool.html
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Attenuated, doxycycline-inducible molecular clones
human
immunodeficiency
virus
proviral
Inventor(s): Smith, Stephen M.; (Essex Fells, NJ) Correspondence: Roberts Abokhair & Mardula; Suite 1000; 11800 Sunrise Valley Drive; Reston; VA; 20191; US Patent Application Number: 20030232060 Date filed: February 28, 2003 Abstract: The present invention provides an attenuated HIV vaccine comprising an HIV virus modified to replicate only in the presence of at least one tetracycline analogue. Additionally, the present invention provides a method for immunization of humans against HIV which comprises administering to a human a vaccine including an HIV virus modified to replicate only in the presence of at least one tetracycline analogue. Simultaneously, at least one tetracycline analogue is administered for a period of time to allow replication of the modified HIV virus in vivo sufficient to produce immunity. Preferably, the tetracycline analogue is doxycycline. A replication competent HIV-DoxT virus genome which can be controlled by the presence or. absence of doxycycline is produced by preparing a promoter, TetopTCAT; producing a provirus, pHIV-DoxT, using the TetopCAT promoter, and transfecting the pHIV-DoxT in cell lines in the presence of doxycycline. A replication competent HIV-DoxSp virus genome which can be controlled by the presence or absence of doxycycline is produced by preparing a promoter, TetopSpCAT; producing a provirus, pHIV-DoxSp, using the TetopCAT promoter, and transfecting the pHIV-DoxSp in cell lines in the presence of doxycycline. Anti-HIV vaccines are prepared using the HIV-DoxT and HIV-DoxSp virus genomes. These viruses and doxycycline are administered to human hosts. The doxycycline is administered for a time sufficient to build up immunity and then the administration of the drug is stopped so that the doxycycline-dependent viruses will no longer replicate. Excerpt(s): This application is a continuation in part of copending U.S. application titled Attenuated, Doxycycline-Inducible Human Immunodeficiency Virus Proviral Molecular Clones having Ser. No. 09/624,964 filed on Jul. 25, 2000 which is based upon provisional application No. 60/146,085 and filed on Jul. 28, 1999 which is incorporated herein by reference in its entirety. This invention relates to the field of vaccines. More particularly, this invention is directed to a process for controlling the expression of an HIV provirus to produce a doxycycline-inducible HIV genome. The genome may be used in attenuated HIV vaccines. Vaccination and immunization generally refer to the introduction of a non-virulent agent against which an individual's immune system can initiate an immune response which will then be available to defend against challenge by a pathogen. The immune system identifies invading "foreign" compositions and agents primarily by identifying proteins and other large molecules which are not normally present in the individual. The foreign protein represents a target against which the immune response is made. Web site: http://appft1.uspto.gov/netahtml/PTO/search-bool.html
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Compositions, methods and kits for identying protein-protein interaction disrupting agents Inventor(s): Shen, Shi-Hsiang; (Beaconfield, CA), Zhao, Hui-Fen; (Lasalle, CA) Correspondence: Borden Ladner Gervais Llp; World Exchange Plaza; 100 Queen Street Suite 1100; Ottawa; ON; K1p 1j9; CA Patent Application Number: 20040067483 Date filed: November 17, 2003 Abstract: The present invention provides compositions, methods, and kits for identifying agents that are capable of disrupting protein-protein interaction in a mammalian reverse two-hybrid system. A tetracycline repressor protein was fused with the inhibitory KRAB domain as a suppressor to tightly regulate the reverse two-hybrid system for mammalian cells. Binding of the chimeric protein to the tetracycline operator sequence provided within a promoter entirely suppressed the expression of two interactive proteins. When both an inducer and a candidate protein-protein interaction disrupting agent such as a drug were added in the cell culture together, the reporter gene was either activated by the interaction of protein-pair if the drug was ineffective or remained silent due to the disruption of the protein-protein interaction by the effective drug. The plasmids for the suppressor and the reporter were integrated into chromosomes. Constructs for the expression of interactive proteins were either stably or transiently transfected into the cells. The utility of this system for screening drugs, particularly for enzyme inhibitor drugs, was demonstrated by using two well characterized interactions of the type I receptor for TGF.beta. with FKPB12 and the EGF receptor with p85. The interaction between TGF.beta.BI and FKPB12 or between EGF receptor and p85 were disrupted by FK506 and kinase inhibitor AG1478, respectively. The mammalian reverse two-hybrid system of the present invention can also be used for high throughput screening of compounds that disrupt protein-protein interactions. Excerpt(s): The present invention relates to compositions, methods, and kits for identifying agents that are capable of disrupting protein-protein interaction in mammalian cells. Protein-protein interactions are involved in most biological processes and cellular functions such as the formation of cellular macromolecular structures, receptor and enzyme complexes, and in the regulation of signal transduction pathways. Elucidation of protein-protein interactions in the cell also constitutes an important approach to functional genomics. The most powerful technology for the detection of protein-protein interactions is the yeast two-hybrid system, which was first described by Fields and Song (Nature 340: 245-246. 1989). Protein-protein interactions can be disrupted by certain molecules such as peptides or drugs. At present, the selection of these disrupting molecules for a particular protein-protein interaction is executed using yeast reverse two-hybrid systems (Leanna & Hannink. 1996. Nucleic Acids Res. 24, 3341347; Vital et al. 1996. Proc. Natl. Acad. Sci. USA. 93, 10315-10320; Shih, et al. 1996. Proc. Natl. Acad. Sci. USA.93, 13896-13901) or a bacterial reverse two-hybrid system (Zhang et al. 2000. Nature Biotech. 18, 71-74; Park & Raines. 2000. Nature Biotech. 18, 847-851). Although the yeast and bacterial reverse two-hybrid systems are useful for some genetic selections, they are not ideal systems for screening therapeutic molecules such as drugs as the permeability of these therapeutic molecules in yeast or in bacteria is very different from that in mammalian cells because of difference in cellular compartmentation among yeast, bacteria and mammalian cells. In fact, the potential of drug candidates needs to be evaluated in mammalian cells where such drugs will be used eventually. In addition, various post-translational modifications required for particular protein-protein interactions are limited in both yeast and bacteria. In a mammalian system post-
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translational modification will occur in a natural fashion for particular protein-protein interactions. Presently, there are a few reports of mammalian two-hybrid systems for protein-protein interactions (Luo et al. 2000. U.S. Pat. No. 6,114,111 Shioda et al. 2000. Proc. Natl. Acad. Sci. USA 97, 5220-5224). Web site: http://appft1.uspto.gov/netahtml/PTO/search-bool.html •
Crystal structure of antibiotics bound to the 30S ribosome and its use Inventor(s): Brodersen, Ditlev Egeskov; (Cambridge, GB), Carter, Andrew Philip; (Cambridge, GB), Ramakrishnan, Venkatraman; (Cambridge, GB) Correspondence: Palmer & Dodge, Llp; Kathleen M. Williams; 111 Huntington Avenue; Boston; MA; 02199; US Patent Application Number: 20040034207 Date filed: September 17, 2001 Abstract: The invention provides high resolution X-ray crystal structures of the 30S ribosome, obtained from Thermus thermophilus 30S subunit, having a tetragonal space group P4.sub.12.sub.12 to which are bound an antibiotic selected from the group paromomycin, streptomycin, spectinomycin, tetracycline, pactamycin and hygromycin B. An advantageous feature of the structure is that it diffracts at about 3.ANG. resolution. The invention also provides a crystal of 30S having the three dimensional atomic coordinates of the 30S ribosome, the coordinates being provided in any one of tables 1 to 4. The data may be used for the rational design and modelling of inhibitors for the 30S ribosome, which have potential use as antibiotics. Excerpt(s): This application claims priority from United Kingdom (U.K.) applications 0017376.5 filed Jul. 14, 2000, and 0022943.5 filed Sep. 19, 2000, 0029872.9 filed Dec. 7, 2000, 0029870.3 filed Dec. 7, 2000, 0029871.1 filed Dec. 7, 2000, and 01 10885.1 filed May 3, 2001, the contents of which are incorporated herein by reference. This application is a continuation-in-part of U.S. Ser. No. 09/905,212. The present invention relates to the provision of a high resolution crystal structure of the prokaryotic 30S ribosome subunit, particularly the 30S ribosome subunit bound to various antibiotics, and the use of this structure in drug discovery. The wealth of information made available through efforts in structural genomics and advances in computation has allowed structure-based drug design to emerge as a valuable tool in medicinal chemistry. In the past combinatorial chemistry, coupled with high-throughput approaches, shifted attention away from the more structure-based methods. Large-scale determination of protein structures is reversing the drug discovery process by starting with the protein structure and using it to identify and design new ligands. It is the integration of structure-based methods, virtual screening, and combinatorial chemistry that will provide the basis for more efficient drug design in the future, significantly reducing the time of the design cycle and the cost per marketed drug. Significant advances have already been made in AIDS, arthritis and cancer and in the treatment of hypertension (e.g. captopril). Web site: http://appft1.uspto.gov/netahtml/PTO/search-bool.html
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High efficiency regulatable gene expression system Inventor(s): Lotze, Michael T; (Pittsburgh, PA), Siamak, Agha-Mohammadi; (Pittsburgh, PA) Correspondence: Kirkpatrick & Lockhart Llp; 535 Smithfield Street; Pittsburgh; PA; 15222; US Patent Application Number: 20030221203 Date filed: April 4, 2003 Abstract: Highly efficient regulated promoters (RPs) and transactivators are provided. The RPs contain 2-8 transactivator binding domains positioned in an optimized manner with respect to each other. In a tetracycline-regulatable system, the RP displays 5- to 10fold enhanced regulation efficiency by maintaining high maximal expression while offering 5- to 10-fold reduced basal leakiness. In transient studies, these novel promoters display over 900-fold gene regulation at 1:1 ratio of transactivator to reporter plasmid. Furthermore, these promoters preserve their regulator efficienty in the context of a single positive feedback regulatory vector that presents ease of delivery of the system for many uses, including for use in vivo and in gene therapy. Finally, humanized transactivators are provided, for example a tetracycline transactivator utilizing the human transactivational domain of NF-.kappa.p65 protein fused to tetracycline repressor (terR) is provided that functions as efficiently as the tetracycline-regulated transactivator (tTA) and should reduce the potential immunogenicity of the original tTA. Excerpt(s): This application claims priority to U.S. Provisional Patent Application Serial No. 60/237,633, filed Oct. 3, 2000. Provided is a high efficiency regulatable gene expression system including a promoter and a humanized transactivator. Also provided are methods for inducing expression of a nucleic acid using the regulatable gene expression system. Certain regulatable systems, such as tetracycline-regulatable systems (TRS), offer powerful tools for regulating gene expression. For effective in vivo gene regulation, these systems often suffer from inconsistent delivery and efficiency as double vectors, low efficiency as a single vector, high basal leakiness, and potential immunogenicity. Web site: http://appft1.uspto.gov/netahtml/PTO/search-bool.html
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Manufacture and use of an antibiotic/antibiotics preparation Inventor(s): Kuhn, Klaus-Dieter; (Marburg, DE), Schnabelrauch, Matthias; (Jena, DE), Vogt, Sebastian; (Jena, DE) Correspondence: Kurt Briscoe; Norris, Mclaughlin & Marcus, P.A.; 220 East 42nd Street, 30th Floor; New York; NY; 10017; US Patent Application Number: 20020183265 Date filed: March 19, 2002 Abstract: The present invention concerns the manufacture and use of an antibiotic/antibiotics preparation for human and veterinary medicine, for the treatment of local microbial infections in hard and soft tissue. The manufacture in accordance with the invention of an antibiotic/antibiotics preparation takes place according to the invention in that water, an amphiphilic component of a representative of the alkyl sulfates, aryl sulfates, alkylaryl sulfates, cycloalkyl sulfates, alkylcycloalkyl sulfates,
Patents 197
alkyl sulfamates, cycloalkyl sulfamates, alkylcycloalkyl sulfamates, aryl sulfamates, alkylaryl sulfamates, alkyl sulfonates, fatty acid-2-sulfonates, aryl sulfonates, alkylaryl sulfonates, cycloalkyl sulfonates, cycloalkyl sulfonates, alkylcycloalkyl sulfonates, alkyl disulfates, cycloalkyl disulfates, alkyl disulfonates, cycloalkyl disulfonates, aryl disulfonates, alkylaryl disulfonates, aryl trisulfonates and alkylaryl trisulfonates, one or more antibiotic components from the group of aminoglycoside antibiotics, lincosamide antibiotics and tetracycline antibiotics, an organic auxiliary component and/or an inorganic auxiliary component and if need be at least one biologically active component are mixed together and shaped into molded elements, granulates, powders, foils, shaped masses and threads. Excerpt(s): The present invention concerns the manufacture and use of an antibiotic/antibiotics preparation with delayed active ingredient release for human and veterinary medicine for the treatment of local microbial infections in hard and soft tissues. The treatment of local microbial infections of hard and soft tissue in human and veterinary medicine requires high local antibiotics concentrations in the infected tissue region. It has been known for a long time that a systemic application of antibiotics is encumbered by a series of problems. With systemic use, it is often necessary to use very high antibiotics doses so that antimicrobially effective antibiotics concentrations are attained in the infected tissue. In this way, severe damage to the organism can occur in particular with aminoglucoside antibiotics and with tetracycline type antibiotics owing to their nephrotoxicity and ototoxicity. Therefore the idea of using antibiotics in locally applicable release systems or transferring them in suitable deposit forms suggested itself. Deposit systems for delayed release of antibiotics for the treatment of local infections are the object of a great number of publications and patents. These can generally be classified according to two fundamental retarding mechanisms. The one action principle consists of the physical fixation of the antibiotics through adsorption to a matrix or through inclusion in a non-resorbable or resorbable matrix. The second chemical delay principle consists of using sparingly soluble antibiotic salts which dissolve slowly following appropriate application in the human or animal organism while active ingredients are being released. Web site: http://appft1.uspto.gov/netahtml/PTO/search-bool.html •
Method for producing antibiotic composites Inventor(s): Kuhn, Klaus-Dieter; (Marburg, DE), Schnabelrauch, Matthias; (Jena, DE), Vogt, Sebastian; (Jena, DE) Correspondence: Kurt Briscoe; Norris, Mclaughlin & Marcus, P.A.; 220 East 42nd Street, 30th Floor; New York; NY; 10017; US Patent Application Number: 20020192279 Date filed: March 19, 2002 Abstract: A method for producing antibiotic composites is described, which is characterized in that a salt, which can be subjected to plastic deformation and which consists of at least one cationic component of a protonated antibiotics base from the groups of aminoglycoside antibiotics, the lincosamide antibiotics and the tetracycline antibiotics and of at least one anionic components from the group of organic sulfates and/or organic sulfonates and/or fatty acid esters, is used as a binding agent for the fixation of inorganic composite components and/or possibly organic composite components and possibly for the molding of the composites while adding water, especially through pressing, extrusion, rolling, calendering and grinding processes.
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Excerpt(s): The present invention relates to a method for producing antibiotic composites, which can be used as implants in human and veterinary medicine for treating local microbial infections in hard and soft tissues. It has been long known that a systemic application of antibiotics is associated with a number of problems. The systemic application often makes it necessary to use very high antibiotics dosages in order to be able to achieve antimicrobially effective antibiotics concentrations in the infected tissue. Especially with aminoglycoside antibiotics and tetracycline antibiotics, this can lead to severe injury of the organism due to their nephrotoxic and ototoxic character. Therefore the idea of using antibiotics in locally applicable release systems and/or converting them into suitable delivery forms has been pursued for decades. For the treatment of local microbial infections of soft and hard tissues in human and veterinary medicine, it is particularly important that after the initially high antibiotics dosage, a release of lower antibiotics quantities over a period of days up to several weeks is ensured in order to achieve the largest possible elimination of microorganisms. This is of critical importance especially for infections of the bone tissue to be able to fight the infection successfully. Of particular interest in this context are such composites that, apart from an antibiotic effect, also exhibit osteoconductive effectiveness due to their chemical composition and structure. For the medical application of antibiotic delivery systems it is necessary to formulate the appropriate antibiotics into pharmaceuticals or implants that can be easily handled and stored Through the use of suitable adjuvants. These pharmaceuticals and implants represent composite systems consisting of the respective active substance and the adjuvant that is necessary for the formulation. Web site: http://appft1.uspto.gov/netahtml/PTO/search-bool.html •
Method for reducing systemic effects of aging, effects of aging on the skin, and incidence of skin damage from sun exposure using antibiotics of the tetracycline family Inventor(s): Milstein, Harold J.; (Penn Valley, PA) Correspondence: Jeffrey Racho, ESQ.; Harvey & Mortensen; STE. T-2; 800 Lancaster Avenue; Berwyn; PA; 19312; US Patent Application Number: 20030082120 Date filed: October 24, 2002 Abstract: The present invention is a method of administering an antibiotic of the tetracycline family or a non-antibacterial tetracycline compound in a daily dosage over an extended period of time in order to reduce the effects of aging on a patient's skin, including the appearance of wrinkles; to reduce the systemic effects of aging on the patient, including the incidence of hair loss in men, where such systemic effects appeared to be replaced by a general feeling of vigor, increased energy levels and a more youthful physique; to reduce the effects of sun damage on a patient's skin; to reduce the onset of menopause on female patients; to reduce the incidence of myocardial infarction; to reduce the physiological effects of hypertension; to reduce the incidence stroke, and to reduce the high levels of cholesterol in the patient's bloodstream. Excerpt(s): This nonprovisional patent application claims the benefit of the filing date of provisional application No. 60/348,928, filed Oct. 26, 2001, which is herein incorporated by reference. No Federally sponsored research or development was requested for, accepted, or used in the development related to the invention herein claimed. The tetracycline family of antibiotics comprises broad spectrum antibiotics that are effective
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against many different bacteria species as well as other species of microorganisms. Tetracyclines exhibit antibacterial effects by inhibiting the ability of the targeted microbe to produce certain proteins. The tetracycline family includes widely prescribed antibiotics such as doxycycline, minocycline, tetracycline, and oxytetracycline. Web site: http://appft1.uspto.gov/netahtml/PTO/search-bool.html •
Method for the antibiotic coating of bodies with interconnecting microcavities as well as coated bodies and their usage Inventor(s): Kuhn, Klaus-Dieter; (Marburg, DE), Schnabelrauch, Matthias; (Jena, DE), Vogt, Sebastian; (Jena, DE) Correspondence: Kurt G. Briscoe; Norris Mclaughlin & Marcus; 30th Floor; 200 East 42nd Street; New York; NY; 10017; US Patent Application Number: 20030049324 Date filed: June 19, 2002 Abstract: The invention relates to a method for the antibiotic coating of bodies with interconnecting microcavities as well as bodies coated this way and their usage. The invented method is characterized in that in the microcavities of non-metallic bodies an aqueous solution 1, which contains at least one easily water-soluble antibiotic component from the groups of the aminoglycoside antibiotics, the tetracycline antibiotics, the lincosamide antibiotics and the 4-quinolone antibiotics, and an aqueous solution 2, which contains at least one easily water-soluble amphiphilic component from the groups of the alkyl sulfates, alkyl sulfonates, alkylaryl sulfates, dialkylaryl sulfates, alkylaryl sulfonates, dialkylaryl sulfonates, cycloalkyl sulfates, cycloalkyl sulfonates, alkylcycloalkyl sulfates, are introduced, wherein between the introduction of solutions 1 and 2 the water is basically removed through vaporization and/or evaporation, and whereby from the components of solutions 1 and 2 in the microcavities a deposit is formed, which is sparingly soluble in water. Excerpt(s): The present invention relates to a method for the antibiotic coating of bodies with interconnecting microcavities through treatment with a 2-component system as well as such a body and its usage. Bone defects occur relatively frequently in human and veterinary medicine and are caused in particular through bone fistulas, comminuted fractures and tumors. In the case of open comminuted fractures, frequently additional infections of the bone tissue are observed. The treatment of bone defects can occur through a filling process with suitable implants. Over the last few years, in particular porous implants, which due to their chemical composition and their porous structure have an osteo-conductive effect and favor a growing in with the surrounding bone tissue, have gained interest. The treatment of bone defects becomes problematic whenever additional microbial infections of the bone tissue exists. Infections of the bone tissue can be counteracted through the systemic or local application of suitable antibiotics. The systemic application of antibiotics is problematic due to the in part not inconsiderable toxicity of the antibiotics. The local application directly in or on the infected tissue on the other hand offers the advantage that high local antibiotics concentrations can be achieved while avoiding damaging antibiotics concentrations in the remaining organism. These high local antibiotics concentrations at the location of the bacterial infections allow the microorganisms to be killed almost completely so that the bacterial infections can be treated very efficiently. It is particularly advantageous if at the location of the bacterial infection an effective antibiotic concentration is maintained over the course of several days to weeks so as to allow the antibiotic to penetrate into the
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infected tissue as deeply as possible and thus destroy even germs that are difficult to access. Soft tissue defects with bacterial infections can also be found frequently in human and veterinary medicine. Local antibiotics treatment is therefore also of interest for the treatment of these types of infections. Until now, sparingly soluble salts of the aminoglycoside antibiotics, the tetracycline antibiotics and the lincosamide antibiotics met with relatively little interest in the production of controlled-release drugs and of antibiotically effective implants. The synthesis of sparingly soluble salts or chelates of the antibiotics of the tetracycline type has been general knowledge for decades. Folch Vazquez for example describes the production of tetracycline dodecyl sulfate through the conversion of tetracycline hydrochloride with sodium dodecyl sulfate in water (C. Folch-Vazquez: Tetracycline lauryl sulfate. Feb. 8, 1966, ES 3309402; C. Folch Vazquez: Tetracycline derivatives. Jan. 9, 1967, NL 6609490). Web site: http://appft1.uspto.gov/netahtml/PTO/search-bool.html •
Method for treating meibomian gland disease Inventor(s): Lokeshwar, Balakrishna L.; (Miami, FL), Pflugfelder, Stephen C.; (Miami, FL), Selzer, Marie; (Fort Lauderdale, FL) Correspondence: Venable, Baetjer, Howard And Civiletti, Llp; P.O. Box 34385; Washington; DC; 20043-9998; US Patent Application Number: 20030114426 Date filed: August 22, 2002 Abstract: A method for treating a patient having meibomian gland disease, ocular irritation associated with delayed tear clearance, or recurrent corneal epithelial erosion, is disclosed. Preferably, the method concerns treatment of a patient with topical tetracycline, a derivative or analogue of tetracycline, or a chemically modified tetracycline (CMT). Oral administration of a CMT is also disclosed as part of the method for treating meibomian gland disease, ocular irritation associated with delayed tear clearance, or recurrent corneal epithelial erosion. Excerpt(s): Meibomian gland disease is the most common tear film and ocular surface disorder causing eye irritation. The incidence of the disease increases with age, and occurs in approximately 50% of patients with the skin disease, rosacea. A conservative estimate of the number of patients affected with this condition is 10 million in the United States alone. It has been reported that 15% of patients with ocular rosacea develop recurrent corneal epithelial erosions, a potentially sight-threatening problem. Common complaints of patients suffering from meibomian gland disease include blurred or filmy vision, burning or foreign body sensations in the eye, photophobia, and pain severe enough to awaken the person from sleep. Although patients with this condition usually have normal production of aqueous tears by their lacrimal glands, their meibomian glands can atrophy and this is frequently accompanied by metaplasia of the ductal epithelium of these glands. Anterior erosion of the mucocutaneous junction of the eyelid is often noted, as well as eyelid and conjunctival infection, eyelid margin irregularity, corneal epithelial changes, and corneal vascularization. The mechanisms responsible for the eyelid and ocular surface changes and irritation symptoms experienced by patients with meibomian gland disease were heretofore unknown. Therefore, previous treatments of meibomian gland disease were directed only to treatment of presumed infection of the eyelids or meibomian glands, or had particular disadvantages that made such treatments of little use for long periods of time. For example, patients with meibomian gland disease have been symptomatically treated
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with artificial tears, but these agents provide limited, if any, improvement. Topically applied steroids to the eyelids or ocular surface are effective as short-term pulse therapies. However, steroids are not good long-term solutions because of the potential side-effects e.g., cataract and glaucoma. Meibomian gland disease is currently not curable or reversible; therefore, patients with this condition must be treated for life. Web site: http://appft1.uspto.gov/netahtml/PTO/search-bool.html •
Method of treating neurologic disorders Inventor(s): Duncan, Ian D.; (Madison, WI) Correspondence: Michael Best & Friedrich, Llp; One South Pinckney Street; P O Box 1806; Madison; WI; 53701 Patent Application Number: 20030203881 Date filed: March 6, 2003 Abstract: The invention provides a method of treating certain neurological diseases by administering to a patient in need thereof an effective amount of a tetracycline compound. Excerpt(s): This application claims the benefit of priority from International Application No. PCT/US01/27593, filed Sep. 6, 2001, which claims priority to U.S. Provisional Application 60/230,350, filed Sep. 6, 2000, which is incorporated herein by reference. This invention relates to a method of treating neurologic disorders including Alzheimer's disease, Guillain Barr Syndrome, adreneoleukodystrophy, Parkinson's disease, and amyotrophic lateral sclerosis, by administering an effective amount of a tetracycline compound. Alzheimer's disease is probably the best known central nervous system (CNS) disorder. It is the most prevalent human neurodegenerative disease and creates untold human suffering at a huge social and economic cost worldwide. The cause of the disease is unknown and there are no cures nor, indeed, treatments that in any way ameliorate the disease course. Affected patients develop classic brain changes with the formation of amyloid plaques, neurofibrillary tangles, inflammation and degeneration of neurons. As a result of these changes, patients develop progressive memory loss that leads to dementia and total reliance on others. Web site: http://appft1.uspto.gov/netahtml/PTO/search-bool.html
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Methods and apparatus for adhering musculoskeletal tissues Inventor(s): Ferree, Bret A.; (Cincinnati, OH) Correspondence: John G. Posa; Gifford, Krass, Groh, Sprinkle,; Anderson & Citkowski, P.C.; Suite 400, 280 N. Old Woodward AVE.; Birmingham; MI; 48009-5394; US Patent Application Number: 20030192554 Date filed: April 11, 2003 Abstract: A method of adhering musculoskeletal tissues such as tendons, ligaments, and cartilage involves applying one or more substances to enhance adhesion. According to one aspect, scar-forming substances are applied to the tissues that the surgeon wishes to connect. For example, tetracycline, nitrogen mustard, sterile talcum powder, erythromycin, or alternative substances may be applied to the tissues. A second aspect of the invention uses growth factors such as those found in platelet-rich plasma (PRP) to
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accelerate the healing. The growth factors could be sprayed onto the tissues the surgeon wishes to connect. A third aspect uses "glue" such as "fibrin glue" to bond the tissues together. Regardless of the embodiment, an inventive retractable catheter may be used to administer the agent(s) so as not to expose unintended areas. Excerpt(s): This application claims priority from U.S. Provisional Patent Application Serial No. 60/371,903, filed Apr. 11, 2002, the entire content of which is incorporated herein by reference. This invention relates generally to spinal surgery and, in particular, for adhering musculoskeletal tissues. According to current practice, musculoskeletal tissues such as tendons, ligaments, and cartilage are connected surgically with sutures and staples. Generally, the synthetic staples and sutures provide provisional fixation. Long-term connection of the tissues is dependent upon the tissues healing together, however. The natural healing process relies on the formation of fibrous scar tissue between the surgically connected tissues. In a sense, there is a race between failure of the suture and the formation of scar tissue with sufficient tensile strength to hold the tissues together. At times a patient's anatomy can make suturing or stapling of tissues difficult. For example, a surgeon may wish to connect two or more tissues inside a structure such as the intervertebral disc. Web site: http://appft1.uspto.gov/netahtml/PTO/search-bool.html •
Methods and devices for treating aneurysms Inventor(s): Andreas, Bernard; (Redwood City, CA), Chew, Sunmi; (San Jose, CA), Deem, Mark; (Mountain View, CA), French, Ron; (Santa Clara, CA), Gifford, Hanson S. III; (Woodside, CA), Sutton, Doug; (Pacifica, CA) Correspondence: Townsend And Townsend And Crew, Llp; Two Embarcadero Center; Eighth Floor; San Francisco; CA; 94111-3834; US Patent Application Number: 20040073190 Date filed: July 1, 2003 Abstract: Methods and devices provide delivery of one or more therapeutic agents to a treatment site at or near an aneurysm, such as an abdominal aortic aneurysm ("AAA"). Methods typically include placing a device at or near the AAA and releasing one or more therapeutic agents from the device. This may also involve releasing multiple agents in sequential fashion. Examples of possible therapeutic agents include doxycycline, roxithromycin, tetracycline, tetracycline derivatives, and collagen promoting agents, such as propranolol. Devices used to deliver one or more therapeutic agents may include stents, grafts, stent grafts, balloons with perforations and/or needles, expandable wire baskets, drug-eluting capsules, or suitable combinations thereof. One embodiment includes a stent graft with a distally-extending skirt and an supra-renal anchor. Excerpt(s): The present application is a non-provisional of U.S. Patent Application Serial No. 60/393,697 (Attorney Docket No. 020979-000500), filed Jul. 2, 2002, the full disclosure of which is incorporated herein by reference. The present invention relates to methods and devices for treating aneurysms. More particularly, the invention relates to methods and devices for treating abdominal aortic aneurysms by delivering one or more therapeutic agents at or near the aneurysm. An aneurysm is a sac formed by localized dilatation of the wall of an artery, a vein, or the heart. Common areas where aneurysms occur and cause potential medical conditions include the coronary arteries, the carotid arteries, various cerebral arteries, and the abdominal aorta. When a local dilatation of a
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vessel occurs, irregular blood flow patterns result, typically leading to clot formation. Typically, the wall of the vessel also progressively dilates and weakens, often resulting in vessel rupture. Vessel rupture, in turn, often causes dramatic negative health consequences such as a stroke, when a cerebral vessel ruptures, or even death, when an abdominal aortic aneurysm ("AAA") ruptures. In light of these consequences, improved treatment methods and devices for aneurysms are constantly being sought. Although the following discussion focuses on AAA treatment, it is equally applicable to aneurysms in other locations. Web site: http://appft1.uspto.gov/netahtml/PTO/search-bool.html •
Methods for producing high titre vectors and compositions used in such methods Inventor(s): Ellard, Fiona Margaret; (Berkshire, GB), Kingsman, Alan John; (Oxford, GB), Mitrophanous, Kyriacos Andreou; (Oxford, GB), Olsen, John C.; (Chapel Hill, NC), Rohll, Jonathan; (Oxford, GB) Correspondence: Foley And Lardner; Suite 500; 3000 K Street NW; Washington; DC; 20007; US Patent Application Number: 20030113898 Date filed: April 30, 2002 Abstract: A method for producing viral vectors is described using packaging and producer cell lines is described. The producer cell comprises: (i) a first nucleotide sequence (NS) encoding a toxic viral envelope protein operably linked to a promoter; wherein the promoter is operably linked to at least one copy of a TRE; (ii) a second NS wherein the second NS comprises a sequence encoding a tetracycline modulator; (iii) a third NS encoding a retrovirus nucleocapsid protein; and (iv) a fourth NS comprising a retroviral sequence capable of being encapsidated in the nucleocapsid protein such that the retroviral vector particle titre obtainable from the producer cell is regulatable by tetracycline and an initial stimulus with sodium butyrate or functional analogues thereof. Excerpt(s): The present invention relates to packaging and producer cell lines for producing recombinant viral vectors. In particular, the present invention relates to methods for producing pseudotyped viral vectors with a broad host range which can be produced at sufficient titres in packaging and/or producer cells. Most specifically, the invention relates to the generation of pseudotyped retroviral vectors, from stable producer cell lines, having vesicular stomatitis virus-G protein (VSV-G) as the membrane-associated viral envelope protein. The present invention also relates to VSVG pseudotyped retroviral vectors useful in gene delivery and more specifically, to lentiviral vectors, in particular those derived from equine infectious anaemia virus (EIAV), useful in gene delivery to non-dividing and dividing cells. Retroviruses and vectors derived from them require an envelope protein in order to transduce efficiently a target cell. The envelope protein is expressed in the cell producing the virus or vector and becomes incorporated into the virus or vector particles. Retrovirus particles are composed of a proteinaceous core derived from the gag gene that encases the viral RNA. The core is then encased in a portion of cell membrane that contains an envelope protein derived from the viral env gene. The envelope protein is produced as a precursor, which is processed into two or three units. These are the surface protein (SU) which is completely external to the envelope, the transmembrane protein (TM) which interacts with the SU and contains a membrane spanning region and a cytoplasmic tail (Coffin
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1992 In The Retroviridae, Pleum Press, ed Levy). In some retroviruses a small peptide is removed from the TM. Web site: http://appft1.uspto.gov/netahtml/PTO/search-bool.html •
Methods of disease treatment using metal-complexed tetracycline antibiotics Inventor(s): Isbister, Jenefir; (Potomac, MD) Correspondence: Carella, Byrne, Bain, Gilfillan,; Cecchi, Stewart & Olstein; 6 Becker Farm Road; Roseland; NJ; 07068; US Patent Application Number: 20030171340 Date filed: February 5, 2003 Abstract: A method for treating bacterial diseases, including bacterial infections, that are otherwise resistant to antibiotics, such as tetracycline and related compounds, using metal-complexed antibiotics is disclosed. Also disclosed is a method for protecting against such diseases. The metal-complexed antibiotics include tetracyclines complexed with metals such as iron, copper and calcium. Excerpt(s): This application claims priority of U.S. Provisional Application Serial No. 60/355,560, filed Feb. 7, 2002, the disclosure of which is hereby incorporated by reference in its entirety. This invention relates to a method of treating antibiotic, especially cycline and quinolone antibiotic, resistant bacterial infections using metal complexed cyclic antibiotics, such as metal-complexed tetracycline. A wide variety of antibiotics have been used to combat bacterial infection while the development of antibiotic resistance continues to increase. The latter problem has been largely the result of both misuse and overuse of antibiotics and therapeutic agents, which serves to select for microorganisms carrying the relatively rare trait(s) providing resistance to these same antibiotics. This selection method results in a higher frequency of the traits providing resistance and a population of antibiotic resistant microorganisms. Most resistance determinants can be transferred to other bacteria via plasmids and transposons exchanged by cell-cell contact, by free naked DNA from lysed cells, and by bacteriophages. This capacity for genetic transfer, coupled with the selective ability of antibiotics results in the presence of common genes in diverse microorganisms from different ecological and geographical niches. In sum, antibiotics select for the survivors which then thwart their efficacy. (see: Levy et al, 1999). Web site: http://appft1.uspto.gov/netahtml/PTO/search-bool.html
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Methods of preparing substituted tetracyclines with transition metal-based chemistries Inventor(s): Koza, Darrell J.; (Westerly, RI), Nelson, Mark L.; (Wellesley, MA), Rennie, Glen; (Weymouth, MA) Correspondence: Lahive & Cockfield, LLP.; 28 State Street; Boston; MA; 02109; US Patent Application Number: 20040033996 Date filed: July 9, 2003 Abstract: The present invention relates to novel chemistries which allow for heretofore unobtainable substituted tetracycline compounds which exhibit significant antibacterial activity. The methods disclosed herein utilize reactive tetracycline-based precursor
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compounds, reactive organic substituent precursors and transition metal catalysts under conditions such that a tetracycline compound substituted with the desired organic substituent is formed. In one embodiment of the invention, a substituted tetracycline compound may be prepared by combining a reactive tetracycline-based precursor compound such as an arene tetracycline diazonium salt, and a reactive organic substituent precursor, e.g., alkenes, substituted alkenes, vinyl monomers, aromatics and heteroaromatics, in the presence of a transition metal catalyst, such as palladium chloride, under conditions such that a tetracycline compound substituted with the organic substituent is formed. Such compounds may optionally act as intermediates for making other compounds, e.g., hydrogenation of unsaturated groups on the substituent. Excerpt(s): This application is a divisional of U.S. Ser. No. 09/660,598, filed on Sep. 13, 2000, Issuing, which claims the benefit of priority under 35 U.S.C. 119(e) to copending U.S. Provisional Application No. 60/154,701, filed on Sep. 14, 1999, and U.S. Provisional Application No. 60/232,091, filed Sep. 12, 2000, the entire contents of each of which are incorporated herein by reference. More recent research efforts have focused on developing new tetracycline antibiotic compositions effective under varying therapeutic conditions and routes of administration; and for developing new tetracycline analogues which might prove to be equal or more effective then the originally introduced tetracycline families beginning in 1948. Representative of such developments include U.S. Pat. Nos. 3,957,980; 3,674,859; 2,980,584; 2,990,331; 3,062,717; 3,557,280; 4,018,889; 4,024,272; 4,126,680; 3,454,697; and 3,165,531. It will be understood that these issued patents are merely representative of the range of diversity of investigations seeking tetracycline and tetracycline analogue compositions which are pharmacologically active. Historically, soon after their initial development and introduction, the tetracyclines, regardless of specific formulation or chemical structure, were found to be highly effective pharmacologically against rickettsiae; a number of gram-positive and gram-negative bacteria; and the agents responsible for lymphogranuloma venereum, inclusion conjunctivitis, and psittacosis. Hence, tetracyclines became known as "broad spectrum" antibiotics. With the subsequent establishment of their in vitro antimicrobial activity, effectiveness in experimental infections, and pharmacological properties, the tetracyclines as a class rapidly became widely used for therapeutic purposes. However, this widespread use of tetracyclines for both major and minor illnesses and diseases led directly to the emergence of resistance to these antibiotics even among highly susceptible bacterial species both commensal and pathogenic--as for example pneumococci and Salmonella. The rise of tetracycline-resistant organisms has resulted in a general decline in use of tetracyclines and tetracycline analogue compositions as antibiotics of choice. Web site: http://appft1.uspto.gov/netahtml/PTO/search-bool.html •
Methods of simultaneously treating ocular rosacea and acne rosacea Inventor(s): Ashley, Robert A.; (Newton, PA) Correspondence: Irving N. Feit, ESQ.; Hoffmann & Baron, Llp; 6900 Jericho Turnpike; Syosset; NY; 11791; US Patent Application Number: 20030229055 Date filed: April 16, 2003 Abstract: A method for simultaneously treating ocular rosacea and acne rosacea in a human in need thereof comprising administering systemically to said human a
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tetracycline compound in an amount that is effective to treat ocular rosacea and acne rosacea but has substantially no antibiotic activity. Excerpt(s): The present application claims benefit of U.S. provisional application serial No. 60/373,141, filed Apr. 16, 2002, which is incorporated herein by reference. Ocular rosacea is a common tear film and ocular surface disorder causing eye irritation. This disorder is characterized by eye surface inflammation, and a variety of related eye disorders such as blepharitis; meibomian gland disease, including meibomian gland dysfunction and meibomianitis; keratitis; conjunctival hyperemia; and eyelid hyperemia. A conservative estimate of the number of patients affected with ocular rosacea is 10 million in the United States alone. It has been reported that 15% of patients with ocular rosacea develop recurrent corneal epithelial erosions, a potentially sightthreatening problem. The incidence of ocular rosacea increases with age. Web site: http://appft1.uspto.gov/netahtml/PTO/search-bool.html •
Modified tetracycline repressor protein compositions and methods of use Inventor(s): Hillen, Wolfgang; (Uttenreuth, DE) Correspondence: Pennie And Edmonds; 1155 Avenue OF The Americas; New York; NY; 100362711 Patent Application Number: 20030186281 Date filed: December 20, 2002 Abstract: The present invention relates to a system for regulating gene expression in prokaryotes using modified tetracycline repressor proteins. In particular, the present invention relates to modified tetracycline repressor proteins that exhibit a "reverse" phenotype in prokaryotic organisms, nucleic acids encoding these repressor proteins, methods for identifying and preparing these proteins, and methods for using these proteins for regulating gene expression in prokaryotic organisms, in drug screening assays and for identifying non-antibiotic compounds that are specific inducers of these modified repressor proteins. Excerpt(s): This application claims the benefit of priority of U.S. provisional application serial No. 60/343,278, filed Dec. 21, 2001, which is incorporated herein by reference, in its entirety. Increased resistance of pathogenic organisms to conventional antibiotics is a serious clinical problem confronting physicians and health care providers. Resistance to tetracycline (tet), a broad spectrum antibiotic that inhibits bacterial protein chain elongation, is one of the most common forms of antibiotic resistance encountered in bacteria, and at least three mechanisms have been described for conferring resistance: active efflux of tetracycline from the cell, protection of the ribosomal protein target and chemical degradation of the drug (for a general review of tetracycline resistance, see Hillen & Berens, (1994) Annu. Rev. Microbiol. 48:345-369). Web site: http://appft1.uspto.gov/netahtml/PTO/search-bool.html
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Multivalent macrolide antibiotics Inventor(s): Griffin, John H.; (Atherton, CA), Pace, John L.; (San Anselmo, CA) Correspondence: Theravance, INC.; 901 Gateway Boulevard; South San Francisco; CA; 94080; US Patent Application Number: 20030176670 Date filed: December 27, 2002 Abstract: Disclosed are multibinding compounds which include macrolide antibiotics, aminoglycosides, lincosamides, oxazolidinones, streptoramins, tetracycline and/or other compounds which bind to bacterial ribosomal RNA and/or to one or more proteins involved in ribosomal protein synthesis in the bacterium, which are useful in treating bacterial infections. The compounds adversely affect protein expression and have an antibacterial effect. The multibinding compounds of this invention containing from 2 to 10 ligands covalently attached to one or more linkers. Each ligand is macrolide antibiotic, aminoglycoside, lincosamide, oxazolidinone, streptogramin, tetracycline or other compound which binds to bacterial ribosomal RNA and/or one or more proteins involved in ribosomal protein synthesis in the bacterium. Excerpt(s): This application claims the benefit of U.S. Provisional Patent Application Serial Nos. 60/088,448 filed Jun. 8, 1998 and 60/093,072 filed Jul. 16, 1998 both of which are incorporated herein by reference in their entirety. This invention relates to novel multibinding compounds (agents) that are macrolide antibiotics, aminoglycosides, lincosamides, oxazolidinones, streptogramins, tetracyclines or other compounds which bind to bacterial ribosomal RNA or one or more proteins involved in ribosomal protein synthesis in the bacterium, and to pharmaceutical compositions comprising such compounds. The compounds are useful as antibacterial agents for treating a variety of bacterial infections. Organisms generate polypeptides (proteins) in order to survive. Organisms that cannot generate proteins cannot maintain viability. Because the majority of genes encode proteins, "gene expression" is nearly synonymous with protein synthesis. Gene expression involves two steps--transcription and translation. Genes code for proteins using various codons (units of three nucleotides), such as start codons (which initiate translation), stop codons (which stop translation) and codons in between the start and stop codons which selectively code for the various amino acids. Web site: http://appft1.uspto.gov/netahtml/PTO/search-bool.html
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Novel Tet repressor-based transcriptional regulatory proteins Inventor(s): Bujard, Hermann; (Heidelberg, DE), Hillen, Wolfgang; (Erlangen, DE) Correspondence: Lahive & Cockfield; 28 State Street; Boston; MA; 02109; US Patent Application Number: 20030208783 Date filed: June 5, 2003 Abstract: The present invention provides a panel of transcriptional activator fusion proteins which comprises both tetracycline controlled transactivator proteins and reverse tetracycline transactivator proteins. These transactivators have novel phenotypes such as altered basal transcriptional activity in the absence of doxycycline, altered induced transcriptional activity in the presence of doxycycline, or differential induction by tetracycline and analogs of tetracycline.
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Excerpt(s): This application claims priority to U.S. Provisional Application No. 60/137,986, filed on Jun. 7, 1999, incorporated herein in its entirety by this reference. The Tn10-encoded Tet repressor (TetR) protein regulates the expression of tetracycline resistance genes in gram negative bacteria, e.g., Escherichia coli, in a tetracycline (Tc) dependent fashion (reviewed in Hillen & Berens, 1994). In the absence of Tc, a TetR protein dimer binds to operator sequences (tetO) and inhibits expression of the tetracycline resistance gene (tetA). When the inducer Tc enters the cell and binds to TetR, the affinity for tetO is reduced and TetR dissociates from tetO, allowing expression of tetA. The crystal structures of the TetR-[Mg--Tc].sup.+ complex (Hinrichs et al., 1994; Kisker et al., 1995) and free TetR (Orth et al., 1998), and analysis of noninducible TetR mutants (Muller et al., 1995), imply that the binding of Tc induces conformational changes in TetR. Dimerization of TetR is mediated by a four helix bundle, and residues which determine the dimerization specificity have been identified (Schnappinger et al, 1998). This has led to TetR based regulators which cannot heterodimerize. TetR-based transcription activators have been developed which allow inducible expression of appropriately modified genes in a tetracycline dependent mode (Gossen & Bujard, 1992; Gossen et al, 1995) in various cellular systems of mammalian (Gossen & Bujard, 1992), plant (Weinmann et al, 1994; Zeidler et al, 1996) and amphibian (Camacho-Vanegas et al., 1998) origin, as well as in whole organisms including fungi (Gari et al., 1997), plants (Weinmann et al., 1994), Drosophila (Bello et al., 1998), mice (Kistner et al., 1996; Efrat et al., 1995; Ewald et al., 1996) and rats (Fishman et al., 1994; Harding et al., 1998). Web site: http://appft1.uspto.gov/netahtml/PTO/search-bool.html •
Pharmaceutical preparation, method for its production as well as its use Inventor(s): Kuhn, Klaus-Dieter; (Marburg, DE), Schnabelrauch, Matthias; (Jena, DE), Vogt, Sebastian; (Jena, DE) Correspondence: Kurt Briscoe; Norris, Mclaughlin & Marcus, P.A.; 220 East 42nd Street, 30th Floor; New York; NY; 10017; US Patent Application Number: 20040067253 Date filed: June 20, 2003 Abstract: The invention relates to hardly soluble antiphlogistic salts and antiphlogisticantibiotic pharmaceutical preparations and their use. The hardly water soluble antiphlogistic antibiotics salts have as their cationic component one of the antibiotics gentamicin, clindamycin, neomycin, streptomycin, tetracycline, doxicyline, oxytetracycline and rolitetracycline and as their anionic component one of the antiphlogistics ibuprofen, naproxen, indomethacin, dexamethasone-21-phosphate, dexamethasone-21-sulfate, triamcinolone-21-phosphate and triamcinolone-21-sulfate. The antiphlogistic antibiotics salts are used in pharmaceutical preparations as controlled-release antibiotic/antibiotics drugs. The invention describes antiphlogisticantibiotic pharmaceutical preparations for which mixtures in the solid state of aggregation are used, which are composed of an easily water soluble salt of gentamicin, clindamycin, neomycin, streptomycin, tetracycline, doxicycline, oxytetracycline and/or rolitetracycline and at least one easily water soluble salt of ibuprofen, naproxen, indomethacin, dexamethasone-21-phosphate, dexamethasone-21-sulfate, triamcinolone21-phosphate and/or triamcinolone-21-sulfate and at least one inorganic and/or organic pharmaceutical adjuvant and which are used as permanent or temporary implants in the form of tablets and/or molded bodies.
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Excerpt(s): The present invention relates to pharmaceutical preparations, their production as well as their use in human and veterinary medicine for the treatment and prevention of local bacterial infections. The treatment of local microbial infections of soft and hard tissues in human and veterinary medicine requires high local concentrations of antibiotics in the infected tissue area. It has been known for quite some time that the systemic application of antibiotics is associated with a series of problems. The systemic application often requires the use of very high doses of antibiotics in order to achieve anti-microbially effective antibiotics concentrations in the infected tissue. Thus, particularly with the use of aminoglycoside antibiotics, severe damage to the organism can occur due to their nephro- and oto-toxicity. It therefore seems reasonable to use antibiotics in topical release systems, or transfer them into suitable controlled-release preparations. It is furthermore generally known that especially local microbial infection processes are associated with distinct inflammation processes of the infected tissue, which can lead to additional damage of the infected organism. It is therefore beneficial to take action with antibiotics for local microbial infections as well as for microbial pathogens and simultaneously treat the inflammatory processes. Controlled-release preparations for the delayed release of antibiotic active ingredients used in the treatment of local infections are the objects of a variety of publications and patents. Apart from physical retarding systems where the retarding effect is essentially based on adsorption effects and diffusion processes, we also know of some retarding systems on the basis of slightly soluble antibiotics salts and antibiotics complexes. Until now hardly soluble salts of the aminoglycoside antibiotics, the tetracycline antibiotics and the lincosamide antibiotics met with relatively little interest in the production of controlled-release preparations. The formation of hardly soluble salts or complexes of the antibiotics of the tetracycline type has been common knowledge for decades. For example the use of tetracycline sulfamates was suggested for antibiotic therapy purposes (A. Jurando Soler, J. M. Puigmarti Codina; Antibiotic tetracycline sulfamate and its derivatives, Oct. 27, 1970, U.S. Pat. No. 3,536,759; Anonymous: Antibiotic tetracycline alkylsulfamates, Oct. 16, 1969, ES 354 173; C. Ciuro, A. Jurado: Stability of a tetracycline derivative. Afinidad 28 (292) 1971, 1333-5). Among the aminoglycoside antibiotics we also basically know a series of hardly soluble salts. For gentamicin, for example, the presentation of hardly soluble salts based on higher fatty acids, arylalkyl carboxylic acids, alkyl sulfates and alkyl sulfonates has been described (G. M. Luedemann, M. J. Weinstein: Gentamycin and method of production, Jul. 16, 1962, U.S. Pat. No. 3,091,572). Examples for this are gentamicin salts of the lauric acid, stearic acid, palmitic acid, oleic acid, phenyl butyric acid, naphthalene-1-carboxylic acid, lauric sulfuric acid and dodecyl benzene sulfonic acid. These salts frequently proved to be not beneficial because they represent wax-like, hydrophobic substances that prevent galenical use. Nevertheless, fatty acid salts were synthesized from gentamicin and from etamycin from the free base and/or their salts in water at 50-80.degree. C. (H. Voege, P. Stadler, H. J. Zeiler, S. Samaan, K. G. Metzger: Sparingly-soluble salts of aminoglycosides and formations containing them with inhibited substance-release, Dec. 28, 1982, DE 32 48 328). These antibiotics fatty acid salts are supposed to be suited as injection preparations. The production of gentamicin dodecyl sulfate and its use in ointments and cremes has also been described (A. Jurado Soler, J. Puigmarti Codina, J. A. Ortiz Hernandez: Neue Gentamicinderivate, Verfahren zur Herstellung derselben und diese enthaltende pharmazeutische Mittel (new gentamicin derivatives, method for production of the same, and pharmaceutical substances containing them), Apr. 21, 1975, DE 25 17 600). Among the lincosamide antibiotics as well hardly soluble salts, such as e.g. glindamycin palmitate, are known (M. Cimbollek, B. Nies, R. Wenz, J, Kreuter: Antibiotic-impregnated heart valve sewing rings for treatment and prophylaxis of bacterial endocarditis. Antimicrob. Agents Chemother. 40(6) (1996) 1432-1437). A more recent development are hardly soluble
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aminoglycoside flavonoid phosphates (H. Wahlig, E. Dingeldein, R. Kirchlechner, D. Orth, W. Rogalski: Flavonoid phosphate salts of aminoglycoside antibiotics, Oct. 13, 1986, U.S. Pat. No. 4,617,293). It describes the salts of the phosphoric acid semi-esters of derivatives of the hydroxy flavanes, hydroxy flavenes, hydroxy flavanones, hydroxy flavones and hydroxy flavylium. Particularly preferred are the derivatives of the flavanones and the flavones. These hardly soluble salts are supposed to be used as controlled-release preparations. These salts are for example introduced into collagen fleece (H. Wahlig, E. Dingeldein, D. Braun: Medicinally useful, shaped mass of collagen resorbable in the body, Sep. 22, 1981, U.S. Pat. No. 4,291,013). Web site: http://appft1.uspto.gov/netahtml/PTO/search-bool.html •
Rapidly disintegrating formulations for treating or preventing mucositis Inventor(s): Lawter, James Ronald; (Yardley, PA) Correspondence: Patrea L. Pabst; Holland & Knight Llp; Suite 2000, One Atlantic Center; 1201 West Peachtree Street, N.E.; Atlanta; GA; 30309-3400; US Patent Application Number: 20040029843 Date filed: June 20, 2003 Abstract: Mucositis is treated and/or prevented by administrating to a patient a rapidly disintegrating solid dosage form comprising a tetracycline. The dosage form may contain another agent such as an NSAID, an inflammatory cytokine inhibitor, a mast cell inhibitor, an MMP inhibitor, an NO inhibitor, or a mixture thereof. The dosage forms may optionally also contain an antifungal agent to prevent fungal overgrowth due to reduction in the normal oral flora by the tetracycline. The tetracycline is preferably one that is poorly absorbed from the gastrointestinal tract. Such compositions have the advantage of treating the entire gastrointestinal tract since the active ingredient is not removed from the tract via absorption. Further, such compositions minimize systemic exposure and accompanying side effects. The compositions can be formulated as solid dosage forms comprising a tetracycline which disintegrates in an aqueous medium or saliva within in a short period, for example, two minutes. The dosage form can be, for example, a hard, compressed tablet adapted to rapidly disintegrate in saliva or an aqueous vehicle or a table prepared by freeze-drying a solution or suspension of the active ingredients. Excerpt(s): Priority is claimed to U. S. Provisional applications Serial No. 60/390,068, filed Jun. 20, 2002, and 60/407,730, filed Sep. 3, 2002, the teachings of which are incorporated herein. The present application relates generally to rapidly disintegrating solid dosage forms containing a tetracycline and optionally other agents that are useful for treating or preventing mucositis, when administered topically to the oral cavity. Mucositis is a dose-limiting side effect of cancer therapy and bone marrow transplantation and is not adequately managed by current treatment (Sonis, 1993a, "Oral Complications," in: Cancer Medicine, pp. 2381-2388, Holand et al.; Eds., Lea and Febiger, Philadelphia; Sonis, 1993b, "Oral Complications in Cancer Therapy," In: Principles and Practice of Oncology, pp. 2385-2394, De Vitta et al., Eds., J. B. Lippincott, Philadelphia). Oral mucositis is found in almost 100% of patients receiving radiotherapy for head and neck tumors, in about 40% of patients receiving chemotherapy, and in about 90% of children with leukemia (Sonis, 1993b, supra). Complications related to oral mucositis, though varying in the different patient populations, generally include pain, poor oral intake with consequent dehydration and weight loss, and systemic infection with organisms originating in the oral cavity leading to septicemnia (Sonis, 1993b; U.S. Pat.
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No. 6,025,326 to Steinberg et al.). In addition to the oral cavity, mucositis may also affect other parts of the gastrointestinal tract. Web site: http://appft1.uspto.gov/netahtml/PTO/search-bool.html •
Reducing tetracycline resistance in living cells Inventor(s): Levy, Stuart B.; (Boston, MA) Correspondence: Lahive & Cockfield; 28 State Street; Boston; MA; 02109; US Patent Application Number: 20030153537 Date filed: February 16, 2000 Abstract: The present invention provides an improved methodology by which therapeutically to overcome resistance to tetracycline in living cells including bacteria, parasites, fungi, and rickettsiae. The methodology employs a blocking agent such as C5 ester derivatives, or 6-deoxy 13-(substituted mercapto) derivatives of tetracycline, in combination with other tetracycline-type antibiotics as a synergistic combination of compositions to be administered simultaneously, sequentially or concurrently. In another embodiment, certain novel compositions are provided which may be administered alone against, for example, a sensitive or resistant strain of gram positive bacteria such as S. aureus and E. faecalis. The concomitantly administered compositions effectively overcome the tetracycline resistant mechanisms present such that the cell is effectively converted from a tetracycline-resistant state to a tetracycline-sensitive state. Excerpt(s): This application is a Continuation-In-Part Application of application Ser. No. 07/788,693 filed Nov. 6, 1991, which is a Continuation-In-Part application of application Ser. No. 07/484,904 filed Feb. 26, 1990, now U.S. Pat. No. 5,064,821 issued Nov. 12, 1991, which is a Continuation-In-Part of application Ser. No. 07/672,323 filed Mar. 20, 1991, which is a Continuation-In-Part of Application Serial No. 06/850,843 filed Apr. 11, 1986, now U.S. Pat. No. 5,021,407 issued Jun. 4, 1991, which is a Continuation of Application Serial No. 06/442,688 filed Nov. 18, 1982, now U.S. Pat. No. 4,806,529 issued Feb. 21, 1989. The research for the present invention was supported by funds obtained through Tufts University. The present invention concerns therapeutic tetracycline treatment of living cells, and is particularly directed to methods and materials for altering and overcoming resistance to tetracycline within microorganisms such as bacteria, fungi, rickettsia, and the like. Web site: http://appft1.uspto.gov/netahtml/PTO/search-bool.html
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Regulable gene expression in Gram-positive bacteria Inventor(s): Shen, Xiaoyu; (Boston, MA), Tally, Francis P.; (Lincoln, MA), Tao, Jianshi; (North Andover, MA), Zhang, Jiansu; (Roslindale, MA) Correspondence: Hamilton, Brook, Smith & Reynolds, P.C.; 530 Virginia Road; P.O. Box 9133; Concord; MA; 01742-9133; US Patent Application Number: 20030054537 Date filed: May 17, 2002 Abstract: A system has been constructed which is suitable for tetracycline-inducible gene expression in Gram-positive bacteria such as Staphylococcus aureus and Bacillus subtilis. The replicon/host gene expression system is tightly regulated, can be used in
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complex as well as minimal media, and can produce a high level of gene expression upon induction, with a variety of gene products. The gene expression system is suitable for production of products toxic to the host cells, and can be used, for example, for the analysis of gene expression and gene products in Gram-positive bacteria, and in a test of the effect of a peptide or polypeptide inhibitor of an S. aureus enzyme on the growth of S. aureus cells in culture or during infection of an animal. Excerpt(s): This application is a divisional of U.S. patent application Ser. No. 09/291,874 filed on Apr. 14, 1999, which is a continuation-in-part of U.S. patent application Ser. No. 09/227,687 filed on Jan. 8, 1999, which claims the benefit of U.S. provisional application Ser. No. 60/070,965 filed on Jan. 9, 1998; U.S. provisional application Ser. No. 60/076,638 filed on Mar. 3, 1998; U.S. provisional application Ser. No. 60/081,753 filed on Apr. 14, 1998; U.S. provisional application Ser. No. 60/085,844 filed on May 18, 1998; U.S. provisional application Ser. No. 60/089,828 filed on Jun. 19, 1998; U.S. provisional application Ser. No. 60/094,698 filed on Jul. 30, 1998; U.S. provisional application Ser. No. 60/100,211 filed on Sep. 14, 1998; U.S. provisional application Ser. No. 60/101,718 filed on Sep. 24, 1998; and U.S. provisional application Ser. No. 60/107,751 filed on Nov. 10, 1998. This application also claims the benefit of U.S. provisional application Ser. No. 60/122,949 filed on Mar. 5, 1999. The teachings of each of these referenced applications are incorporated herein by reference in their entirety. A number of different high and low copy number vector systems using a diversity of regulable promoter systems have been successfully developed to manipulate gene expression in Gram negative organisms such as Escherichia coli. As a result, E. coli can be genetically manipulated in a number of ways that have lead to a thorough understanding of the molecular basis for gene expression and to the elucidation of the function of many important proteins. As a further result, E. coli has been used as a production organism for the high level expression of a number of protein products, some of which are toxic. The majority of these vector systems developed in E. coli, however, do not function properly in Grampositive microorganisms, likely due to physiological differences between Gram-positive and Gram-negative species (de Vos, W. M., et al., Curr. Opin. Biotechnol. 8:547-553, 1997; de Vos, W. M., and G. F. M. Simons, "Gene cloning and expression systems in lactococci," pp. 52-105. In M. J. Gasson and W. M. de Vos (ed.) Genetics and Biotechnology of Lactic Acid Bacteria. Routledge, Chapman and Hall Inc., New York, N.Y., 1994). The lack of vectors providing for the efficiently regulated expression of genes in Gram-positive bacteria has been responsible, in part, for the lack of suitable Gram-positive systems for production of valuable gene products on an industrial scale. The characterization of the biology of Gram-positive bacteria has been hampered by the lack of cloning and expression vector systems that are stably maintained, tightly regulated and inducible, analogous to those developed in E. coli. As a result, the study of important Gram-positive pathogens, that can cause a variety of different illnesses including life threatening ones, has been severely limited, impeding the discovery of novel, life saving therapies to treat infectious diseases. Web site: http://appft1.uspto.gov/netahtml/PTO/search-bool.html
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Single-domain antigen-binding antibody fragments derived from llama antibodies Inventor(s): Dubuc, Ginette; (Ottawa, CA), Narang, Saran; (Ottawa, CA), Tanha, Jasmid; (Ottawa, CA) Correspondence: National Research Council OF Canada; 1500 Montreal Road; Bldg M58, Room Eg12; Ottawa, Ontario; K1a 0r6; CA Patent Application Number: 20030190598 Date filed: November 14, 2002 Abstract: A phage display library of variable heavy domain (V.sub.HH or VH) fragments (sdAb fragments) derived from the antibody repertoire of a non-immunized llama is disclosed. The sdAb fragments of the library are characterized by the absence of cysteine residues in complementarity determining regions (CDRs) and a very low presence of residues of glutamic acid, arginine and glycine at positions 44, 45 and 47 respectively, of the VL interface of the variable heavy domain V.sub.HH. The large size of the library (in the order of 10.sup.9) makes it a source of antigen-binding fragments having high affinity to almost any antigen of interest. The library is preferably generated using a modified fd-tet phage growing in plaques in the absence of a tetracycline. Excerpt(s): The invention relates to antigen-binding proteins, in particular to antigenbinding fragments of antibodies derived from a nave library of llama antibodies and to a phage display library of such fragments. More particularly, the present invention relates to antigen-binding fragments of llama antibodies comprising at least a part of the variable heavy domain (VH or V.sub.HH) of antibodies derived from a nave library of llama antibodies and to a phage display library of such fragments. The immune system in vertebrates provides a defense mechanism against foreign intruders, such as foreign macromolecules or infecting microorganisms. The foreign invaders (antigens), both macromolecules (proteins, polysaccharides, or nucleic acids) and microbes (viruses or bacteria), are recognized through specific binding of the proteins of the host immune system to specific sites on the antigen surface, known as antigenic determinants. As part of the immune system, B-cells of vertebrate organisms synthesize antigen-recognizing proteins known as antibodies or immunoglobulins (Ig). According to the clonal selection theory, an antigen activates those B-cells of the host organism that have on their surface immunoglobulins that can recognize and bind the antigen. The binding triggers production of a clone of identical B-cells that secrete soluble antigen-binding immunoglobulins into the bloodstream. Antibodies secreted by B-cells bind to foreign material (antigen) to serve as tags or identifiers for such material. Antibody-tagged antigens are then recognized and disposed of by macrophages and other effector cells of the immune system or are directly lysed by a set of nonspecific serum proteins collectively called complement. In this way a small amount of antigen can elicit an amplified and specific immune response that helps to clear the host organism of the source of antigen. Through a complex process of gene splicing combined with additional mutation mechanisms, human B-cells have been estimated to produce a "library" (repertoire) of more than a billion (10.sup.9) different antibodies that differ in the composition of their binding sites. Web site: http://appft1.uspto.gov/netahtml/PTO/search-bool.html
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Substituted tetracycline compounds as antifungal agents Inventor(s): Draper, Michael; (Plaistow, NH), Nelson, Mark L.; (Wellesley, MA) Correspondence: Lahive & Cockfield; 28 State Street; Boston; MA; 02109; US Patent Application Number: 20030100017 Date filed: March 14, 2002 Abstract: Methods and compositions for treating fungal associated disorders in subjects are discussed. Excerpt(s): This application claims priority to U.S. Provisional Application Serial No. 60/275,948, filed Mar. 14, 2001, entitled "Substituted Tetracycline Compounds as Antifungal Agents," incorporated herein by reference in its entirety. For many years, the development of effective therapeutic agents for fungal diseases (mycoses) has lacked the attention devoted to drugs effective against other infective organisms. The most common mycotic infections are superficial in nature, are not life threatening, and provide little medical impetus to pharmaceutical companies to develop novel treatments. This scenario is changing, however, and while death from fungal disease is not new, the incidence of systemic fungal infections that cause these fatalities is increasing. Ironically, advances in modern medical techniques in other fields (immunosuppressive and/or cytotoxic therapy) and the advent of disease such as Acquired Immuno Deficiency Syndrome (AIDS) are major contributing causes to the increased number of serious fungal infections. Fungal associated disorders can, thus, be divided into the life-threatening systemic infections, such as histoplasmosis, systemic candidiasis, aspergillosis, blastomycosis, coccidioidomycosis, paracoccidioidomycosis, and cryptococcosis, and the more common superficial ones, such as dermatophyte (ringworm) infections, for example, tinea pedis (athlete's foot) and tinea cruris (jock itch), candidiasis, and actinomycosis. The life-threatening fungal infections are a growing problem not only for immunosuppressed or immunocompromised individuals as noted above but individuals with other viral infections, such as cytomegalovirus (CMV), and influenza, for cancer patients receiving chemotherapy or radiotherapy, for transplant patients receiving antirejection agents, and for patients that have received toxic chemicals, metals and radiation exposure. Web site: http://appft1.uspto.gov/netahtml/PTO/search-bool.html
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Tet transactivator system Inventor(s): Meissner, Markus; (London, GB), Soldati, Dominique; (London, GB) Correspondence: Jonathan P. Osha; Rosenthal & Osha L.L.P.; Suite 2800; 1221 Mckinney Street; Houston; TX; 77010; US Patent Application Number: 20030185851 Date filed: March 20, 2002 Abstract: A transcriptional activator of T. gondii is provided which comprises the tetracycline repressor (TetR) operatively linked to a transacting factor of T. gondii. Strains of T. gondii transformed with a vector containing such a transactivator may be used to prepare vaccine compositions or to identify essential genes in the parasite. The system provided may be useful in other Apicomplexan species such as Plasmodium falciparum, Plasmodium vivax, Plasmodium berghei, Plasmodium yoelii, Plasmodium knowlesi, Trypanosoma brucei, Entamoeba histolytica, and Giardia lambia.
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Excerpt(s): Not applicable. The present invention relates to nucleic acid constructs that can act as inducible transactivator systems in Apicomplexan parasites which can be used to create attenuated strains of the parasites that can act as vaccines to protect against infection by wild-type parasite. The transactivator system also permits the systematic study of the genes in Apicomplexan parasites. Web site: http://appft1.uspto.gov/netahtml/PTO/search-bool.html •
Tetracycline - Doxycycline antibiotic composition Inventor(s): Isbister, James D.; (Potomac, MD), Rudnic, Edward M.; (N. Potomac, MD), Treacy, Donald J. JR.; (Arnold, MD), Wassink, Sandra E.; (Frederick, MD) Correspondence: Elliot M. Olstein, ESQ.; C/o Carella Byrne, Bain, Gilfillan, Cecchi,; Stewart & Olstein; 6 Becker Farm Road; Roseland; NJ; 07068; US Patent Application Number: 20030096008 Date filed: March 7, 2002 Abstract: An antibiotic product for delivering at least Tetracycline or Doxycycline that is comprised of three dosage forms with different release profiles with each of Tetracycline and Doxycycline being present in at least one of the dosage forms. Excerpt(s): This application is a continuation-in-part of application Ser. No. 09/791,983, filed Feb. 22, 2000, which claims the priority of U.S. Provisional Application Serial No. 60/184,545 filed on Feb. 24, 2000, the disclosure of which is hereby incorporated by reference in its entirety. This invention relates to antibiotic compositions and the use thereof. More particularly, this invention relates to a composition for the delivery of two or more antibiotics, and the use thereof. In many cases, it is desirable to employ two different antibiotics in the treatment of a bacterial infection, in that such antibiotics may have complementary mechanisms of action that facilitate treatment of the bacterial infection. Web site: http://appft1.uspto.gov/netahtml/PTO/search-bool.html
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Tetracycline compounds having target therapeutic activities Inventor(s): Draper, Michael; (Plaistow, NH), Jones, Graham; (Needham, MA), Levy, Stuart B.; (Boston, MA), Nelson, Mark L.; (Wellesley, MA) Correspondence: Lahive & Cockfield; 28 State Street; Boston; MA; 02109; US Patent Application Number: 20040063674 Date filed: July 15, 2002 Abstract: Methods and compounds for treating diseases with tetracycline compounds having a target therapeutic activity are described. Excerpt(s): This application claims priority to U.S. Provisional Patent Application Serial No. 60/______, entitled "Methods of Using Substituted Tetracyclines to Treat Inflammatory Process Associated States," filed Jul. 12, 2002; and U.S. Provisional Patent Application Serial No. 60/305,546, entitled "Methods of Using Substituted Tetracyclines to Treat Inflammatory Process Associated States," filed Jul. 13, 2001. The entire contents of each aforementioned applications are hereby incorporated herein by reference in their entirety. Inflammation is the body's reaction to injury and infection. Major events
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involved in inflammatory processes include increased blood supply to the injured or infected area; increased capillary permeability enabled by retraction of endothelial cells; and migration of leukocytes out of the capillaries and into the surrounding tissue (Roitt et al., Immunology, Grower Medical Publishing, New York, 1989). Increased capillary permeability allows larger molecules and cells to cross the endothelium that are not ordinarily capable of doing so, thereby allowing soluble mediators of immunity and leukocytes to reach the injured or infected site. Leukocytes, primarily neutrophil polymorphs (also known as polymorphonuclear leukocytes, neutrophils or PMNS) and macrophages, migrate to the injured site by a process known as chemotaxis. At the site of inflammation, tissue damage and complement activation cause the release of chemotactic peptides such as C5a. Complement activation products are also responsible for causing degranulation of phagocytic cells, mast cells and basophils, smooth muscle contraction and increases in vascular permeability (Mulligan et al. 1991 J. Immunol. 148:1479-1485). Web site: http://appft1.uspto.gov/netahtml/PTO/search-bool.html •
Tetracycline derivatives and methods of use thereof Inventor(s): Ablin, Richard J.; (Ringwood, NJ), Hlavka, Joseph J.; (Tuxedo Park, NY) Correspondence: Duane Morris, Llp; Attn: William H. Murray; One Liberty Place; 1650 Market Street; Philadelphia; PA; 19103-7396; US Patent Application Number: 20040067912 Date filed: October 4, 2002 Abstract: A treatment for inhibiting microbial or tumor growth is disclosed, which comprises adding to a subject in need of treatment an effective amount of one or more tetracycline derivatives. Excerpt(s): The present invention relates to novel tetracycline derivatives, methods for producing the novel derivatives and methods of using these derivatives. Tetracycline as well as the 5-OH (Terramycin) and 7-Cl (Aureomycin) derivatives exist in nature, and are well known antibiotics. Natural tetracycline may be modified without losing their antibiotic properties, although certain elements of the structure must be retained. The modifications that may and may not be made to the basic tetracycline structure have been reviewed by Mitscher in The Chemistry of Tetracyclines, Chapter 6, Marcel Dekker, Publishers, New York (1978). According to Mitscher, the substituents at positions 5-9 of the tetracycline ring system may be modified without the complete loss of antibiotic properties. Changes to the basic ring system or replacement of the substituents at positions 1-4 and 10-12, however, generally lead to synthetic tetracyclines with substantially less or effectively no antimicrobial activity. Some examples of chemically modified non-antimicrobial tetracyclines (hereinafter CMT) are 4dedimethylaminotetraccyline, 4-dedimethylaminosancycline (6-demethyl- 6 -deoxy-4dedimethylaminotetracycline), 4-dedimethylaminominocycline (7-dimethylamino-4dedimethylaminotetracycline), and 4-dedimethylaminodoxycycline (5-hydroxy-6deoxy-4-dedimethyaminotetracycline). Some 4-dedimethylaminotetracycline derivatives are disclosed in U.S. Pat. Nos. 3,029,284 and 5,122,519. They include 6demethyl-6-deoxy-4-dedimethylaminotetraccyline and 5-hydroxy-6-deoxy-4dedimethylaminotetracycline with hydrogen and other substituents at C7, and the C9 positions on the D ring. These substitutents include amino, nitro, di (lower alkyl) amino, and mono (lower alkyl) amino or halogen. The 6-demethyl-6-deoxy-4-
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dedimethylaminotetracycline derivatives and 5-hydroxy-6-deoxy-4dedimethylaminotetracyclin- e derivatives are said to be useful as antimicrobial agents. Web site: http://appft1.uspto.gov/netahtml/PTO/search-bool.html •
Tetracycline-inducible transcriptional inhibitor fusion proteins Inventor(s): Bujard, Hermann; (Heidelberg, DE), Gossen, Manfred; (El Cerrito, CA) Correspondence: Lahive & Cockfield; 28 State Street; Boston; MA; 02109; US Patent Application Number: 20030022315 Date filed: August 3, 2001 Abstract: Methods of regulating gene expression in subjects using tetracyclineresponsive fusion proteins are disclosed. In one embodiment, the method involves introducing into a cell the subject a nucleic acid molecule encoding a fusion protein which inhibits transcription, the fusion protein comprising a first polypeptide which binds to a tet operator sequence, operatively linked to a heterologous second polypeptide which inhibits transcription in eukaryotic cells; and modulating the concentration of a tetracycline, or analogue thereof, in the subject. The first polypeptide can binds to a tet operator sequence in the absence, but not the presence, of tetracycline. Alternatively, the first polypeptide can binds to a tet operator sequence in the presence, but not the absence, of tetracycline. In another embodiment, the method of the invention involves obtaining a cell from a subject, introducing into the cell a first nucleic acid molecule which operatively links a gene to at least one tet operator sequence, introducing into the cell a second nucleic acid molecule encoding an inhibitory fusion protein of the invention to form a modified cell, administering the modified cell to the subject and modulating the concentration of a tetracycline, or analogue thereof, in the subject. The first and second nucleic acid molecules can be linked or can be separate molecules. Excerpt(s): This application is a continuation-in-part of U.S. Ser. No. 08/383,754, filed Feb. 3, 1995. This application is also a continuation-in-part of U.S. Ser. No. 08/275,876, filed Jul. 15, 1994, which is a continuation-in-part of U.S. Ser. No. 08/270,637, filed Jul. 1, 1994, now abandoned. This application is also a continuation-in-part of U.S. Ser. No. 08/260,452, filed Jun. 14, 1994, which is a continuation-in-part of U.S. Ser. No. 08/076,327, filed Jun. 14, 1993, now abandoned. This application is also a continuationin-part of U.S. Ser. No. 08/076,726, filed Jun. 14, 1993. The entire contents of each of these applications are incorporated herein by reference. Functional analysis of cellular proteins is greatly facilitated through changes in the expression level of the corresponding gene for subsequent analysis of the accompanying phenotype. For this approach, an inducible expression system controlled by an external stimulus is desirable. Ideally such a system would not only mediate an "on/off" status for gene expression but would also permit limited expression of a gene at a defined level. Attempts to control gene activity have been made using various inducible eukaryotic promoters, such as those responsive to heavy metal ions (Mayo et al. (1982) Cell 29:99108; Brinster et al. (1982) Nature 296:39-42; Searle et al. (1985) Mol. Cell. Biol. 5:14801489), heat shock (Nouer et al. (1991) in Heat Shock Response, e.d. Nouer, L., CRC, Boca Raton, Fla., pp167-220) or hormones (Lee et al. (1981) Nature 294:228-232; Hynes et al. (1981) Proc. Natl. Acad. Sci. USA 78:2038-2042; Klock et al. (1987) Nature 329:734-736; Israel & Kaufman (1989) Nucl. Acids Res. 17:2589-2604). However, these systems have generally suffered from one or both of the following problems: (1) the inducer (e,g, heavy metal ions, heat shock or steroid hormones) evokes pleiotropic effects, which can
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complicate analyses, and (2) many promoter systems exhibit high levels of basal activity in the non-induced state, which prevents shut-off the regulated gene and results in modest induction factors. Web site: http://appft1.uspto.gov/netahtml/PTO/search-bool.html •
Treatment of psoriasis with matrix metalloproteinase inhibitors Inventor(s): Fleischmajer, Raul; (Barnegat Light, NJ) Correspondence: Baker & Botts; 30 Rockefeller Plaza; New York; NY; 10112 Patent Application Number: 20020198176 Date filed: July 29, 2002 Abstract: The present invention relates to methods of treating psoriasis by inhibiting one or more matrix metalloproteinase enzymes ("MMPs"). It is based, at least in part, on the discovery that the expression patterns of certain MMPs and related molecules are altered in patients suffering from psoriasis, relative to normal subjects. Certain expression patterns are altered even in unaffected skin of psoriasis-afflicted patients, although aberrancies are more pronounced in psoriatic lesions. In various non-limiting embodiments, the present invention provides for methods of treating psoriasis, including preventing the development of new psoriatic lesions, comprising administering, to subjects in need of such treatment, effective concentrations of compounds which inhibit the enzymatic activity of one or more MMP. Suitable inhibitors include tetracycline and its derivatives and various hydroxymate, carboxylic acid, and phosphonic acid derivatives. Therapy may comprise systemic and/or local administration of inhibitor. In additional embodiments, the present invention provides for methods of diagnosing MMP inhibitor responsive skin lesions, for evaluating the level of disease activity in a subject, and for transgenic animal and tissue culture models of psoriasis. Excerpt(s): This application claims priority to U.S. Provisional Patent Application No. 60/186,431, filed Mar. 2, 2000. The present invention relates to methods of treating psoriasis by inhibiting matrix metalloproteinase enzyme(s). It is based, at least in part, on the discovery that the expression of certain matrix metalloproteinase enzyme(s) is increased in the epidermis of patients suffering from psoriasis, and particularly increased in psoriatic skin lesions. Psoriasis is a chronic skin disease characterized by red scaly patches that usually affect the scalp, elbows and knees, although any part of the skin may be involved. At the cellular level, psoriasis is a benign proliferative disease of keratinocytes of unknown etiology. It has been estimated that psoriasis affects about 2 percent of the population in Western countries, 0.1 to 0.3 percent in the Far East and is rather rare in persons of the black race (Krueger et al., 1984, J. Am. Acad. Dermatol. 11:937-947; Yui-Yip, 1984, J. Am. Acad. Dermatol. 10:965-968). Although the disease appears to be inherited, its mode of transmission is not known and more than one genetic locus may be involved (Henseler, 1997, J. Am. Acad. Dermatol. 37:S1-11). Furthermore, the disease can be triggered or exacerbated by external factors such as trauma, infection and drugs. Web site: http://appft1.uspto.gov/netahtml/PTO/search-bool.html
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Triglyceride lowering, common cold and pneumonia prevention composition comprising tetracycline, and methods of treating or preventing diseases using same Inventor(s): Gardner, Wallace J.; (Cambridge, MA) Correspondence: Kevin S. Lemack; Nields & Lemack; Suite 7; 176 E. Main Street; Westboro; MA; 01581; US Patent Application Number: 20040029842 Date filed: April 28, 2003 Abstract: Therapeutic composition having triglyceride blood level lowering activity, total cholesterol blood level lowering activity, LDL blood level lowering activity, HDL blood level raising activity and activity for preventing the common cold and pneumonia. The therapeutic composition is a formulation comprising an antibiotic, preferably a tetracycline, most preferably doxycycline, which optionally has not been chemically modified to eliminate antimicrobial efficacy. The antibiotic is preferably in a liquid vehicle, preferably one that contains at least 20%, most preferably 26% alcohol by volume. The therapeutic composition is preferably in local delivery form and is selfadministered orally. Excerpt(s): This application is a continuation-in-part of Ser. No. 10/023,017 filed on Dec. 18, 2001, the disclosure of which is hereby incorporated by reference. The accumulation of bacteria in the oral cavity, such as on the teeth or tongue has been identified as a contributor or cause of various inflammatory conditions, including gingivitis, periodontitis and other gum diseases. Treatment of the oral cavity with antibiotics to reduce or eliminate the effects of microorganisms is known. For example, broad spectrum antibiotics such as tetracyclines and metronidazole have been used in the treatment of periodontal disease to reduce oral cavity microflora. Typically such use has been systemic, which can result in various undesirable side effects, including the threat or danger of building allergies or immunity to the antibiotic, overgrowth of opportunistic yeast and fungi and intestinal disturbances. Many other common inflammatory diseases, such as sinusitis, diseases of the gastrointestinal tract (including those that manifest themselves in stomach and bowel problems), the common cold, influenza, allergies, halitosis, pneumonia, etc., also may be caused by viruses and/or microorganisms. Often the source of the microorganisms and viruses is the sinuses, typically via the oral cavity, especially the ear, nose and throat passages. Once the microorganisms and/or viruses are resident in the oral cavities or sinuses (e.g., the maxillary, frontal, ethmoid and ophenoidal), they can continually cause inflammation and infection through circulation in the blood stream. Continual reduction or elimination of these microorganisms and viruses would reduce chronic infection in the body. Web site: http://appft1.uspto.gov/netahtml/PTO/search-bool.html
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Use methods of treating acne and telangiectasia Inventor(s): Ashley, Robert A.; (Newtown, PA) Correspondence: Hoffmann & Baron, Llp; 6900 Jericho Turnpike; Syosset; NY; 11791; US Patent Application Number: 20030139380 Date filed: October 15, 2002
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Abstract: A method of treating telangiectasia in a human in need thereof comprising administering to said human a tetracycline compound in an amount that is effective to treat telangiectasia, but has substantially no antibiotic activity. Excerpt(s): This application is a continuation of co-pending U.S. application Ser. No. 10/117,709, filed Apr. 5, 2002. This application claims benefit of U.S. Provisional Application No. 60/281,916, filed Apr. 5, 2001; and U.S. Provisional Application No. 60/325,489, filed Sep. 26, 2001, all of which are incorporated herein by reference. Acne is a common disease characterized by various types of lesions. The areas affected typically are areas of the skin where sebaceous glands are largest, most numerous, and most active. The lesions associated with acne are usually categorized as either noninflammatory or inflammatory. Non-inflammatory lesions include comedones. Comedones appear in two forms, open and closed. Comedones are thought to arise from abnormal follicular differentiation. Instead of undergoing shedding and discharge through the follicular orifice, abnormal desquamated cells (keratinocytes) become unusually cohesive, forming a microcomedo or a microscopic hyperkeratotic plug in the follicular canal. The progressive accumulation of these microcomedones lead to visible comedones. Web site: http://appft1.uspto.gov/netahtml/PTO/search-bool.html •
Use of anabolic agents, anti-catabolic agents, antioxidant agents, and analgesics for protection, treatment and repair of connective tissues in humans and animals Inventor(s): Corson, Barbara E.; (Fawn Grove, PA), Hammad, Tarek; (Baltimore, MD), Henderson, Robert W.; (Baldwin, MD), Henderson, Todd R.; (Jarrettsville, MD), Lippiello, Louis; (Forest Hill, MD), Soliman, Medhat; (Minya, EG) Correspondence: Covington & Burling; 1201 Pennsylvania Avenue, NW; Washington; DC; 20004-2401; US Patent Application Number: 20030129261 Date filed: July 11, 2002 Abstract: The present invention relates to compositions for the protection, treatment and repair of connective tissues in humans and animals comprising any or all of anabolic, anti-catabolic, anti-oxidant and analgesic agents, including aminosugars, Sadenosylmethionine, arachadonic acid, GAGs, including pentosan, collagen type II, tetracyclines or tetracycline-like compounds, diacerin, super oxide dismutase, Lergothionine, one or more avocado/soybean unsaponifiables, and an analgesic, e.g., acetaminophen, and to methods of treating humans and animals by administration of these novel compositions to humans and animals in need thereof. Excerpt(s): In connection with this application, priority is claimed to the following provisional application, A COMPOSITION OF ACETAMINOPHEN, AN AMINOSUGAR AND A GLYCOSAMINOGLYCAN, U.S. Serial No. 60/088,205, filed Jun. 5, 1998. The present application is also a continuation-in-part application of U.S. patent application Ser. No. 09/249,335, filed Feb. 12, 1999, the disclosure of which is hereby incorporated by reference herein in its entirety. That application claimed priority to provisional application: THE USE OF ANABOLIC AGENTS, ANTI-CATABOLIC AGENTS, ANTIOXIDANT AGENTS, AND ANALGESICS FOR PROTECTION, TREATMENT AND REPAIR OF CONNECTIVE TISSUES IN HUMANS AND ANIMALS, U.S. Serial No. 60/074,594, filed Feb. 13, 1998. The present invention relates to compositions for the protection, treatment and repair of connective tissues in humans
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and other animals. The tissues of mammals, including humans, are in a constant state of flux between the anabolic processes that build up tissues, and the catabolic processes which degrade tissues. The state of health exists when there is a balance between these two processes, and derangements of the balance produce disease. This holds true for all tissues of the body. Connective tissues are of particular importance for several reasons. First, they support the "functional cells" of the body, i.e., epithelial, muscle and neural cells. Second, they play critical roles in intercellular communication, which is essential for multicellular life. Web site: http://appft1.uspto.gov/netahtml/PTO/search-bool.html •
Use of non-antibacterial tetracycline analogs and formulations thereof for the treatment of bacterial exotoxins Inventor(s): Golub, Lorne M.; (Smithtown, NY), Walker, Stephen G.; (East Setauket, NY) Correspondence: Hoffmann & Baron, Llp; 6900 Jericho Turnpike; Syosset; NY; 11791; US Patent Application Number: 20040014731 Date filed: March 27, 2003 Abstract: The invention relates to methods for protecting and/or treating a mammal at risk of acquiring a condition associated with bacteria that produce a calmodulin exotoxin, a metalloproteinase exotoxin, or both, by administering a non-antibacterial tetracycline formulation. Excerpt(s): When bacteria attack a host, there is an incubation period during which there are mild or no symptoms. The incubation period varies among bacteria. Once inside the host, some bacteria begin producing exotoxins. These exotoxins damage host tissue and organs, sometimes causing a sudden onset of hyperacute illness which progresses to shock, coma and death. For example, an inhalation infection with Bacillus anthracis (anthrax) can have an incubation period of 3 to 60 days. Death from anthrax inhalation is considered inevitable if untreated, and probable in as many as 95% of treated cases if therapy is begun more than 48 hours after the onset of symptoms. Web site: http://appft1.uspto.gov/netahtml/PTO/search-bool.html
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Use of tetracyclines as neuro-protective agents and for the treatment of parkinson's disease and related disorders Inventor(s): Dodel, Richard; (Marburg, DE), Du, Yansheng; (Carmel, IN) Correspondence: Ratnerprestia; P O Box 980; Valley Forge; PA; 19482-0980; US Patent Application Number: 20030092683 Date filed: November 13, 2001 Abstract: As discussed above the present invention in a first aspect thereof relates to the use of a tetracycline, preferably minocycline, for manufacture of a pharmaceutical composition for treatment or prevention of a disorder selected from Parkinson's disease and related disorders, preferably Parkinson's disease.In a second aspect thereof the invention relates to a method for treating or prevention of a disorder selected from Parkinson's disease and related disorders in a patient in need thereof, which method includes administering the patient an effective dosage of a tetracycline, preferably
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minocycline.In a third aspect thereof the invention relates to the use of a tetracycline, preferably minocycline, as a neuro-protective agent in general. Excerpt(s): Parkinson's disease is a common and disabling neuro-degenerative disorder resulting from the depletion of brain dopamine caused by the dramatic loss of dopaminergic neurons in the substantia nigra pars compacta. The disease is one of the most common neurodegenerative diseases in elderly humans with an occurrence of about 1% of all over 60 years of age. The disease thus causes considerable concerns especially in the western hemisphere. Therapies for Parkinson's disease currently available include dopamine-substitution with levodopa optionally in combination with dopamine agonists. These therapies currently available for Parkinson's disease help alleviate symptoms, however, efficacy is lost over time since progressive loss of dopaminergic neurons continues as the disease progresses. One of the most desirable therapeutic goals for both the treatment as well as prevention of Parkinson's disease, which would be neuro-protection, has been relatively elusive. Accordingly, there are no therapeutic efficacious neuro-protective drugs available to treat Parkinson's disease. Testing of any drugs for treatment and/or prevention of Parkinson's disease is typically carried out in an animal model. In this model Parkinson is induced by administering 1methyl-4-phenyl-1,2,3,6-tetrahydr- opyridine (MPTP), a neurotoxin. MPTP is metabolized into 1-methyl-4-phenylpyridinium (MPP.sup.+) which then selectively kills dopaminergic neurons thereby inducing Parkinsonism. The striking pathologic and clinical similarities between idiopathic Parkinson's disease and MPTP-induced Parkinsonism suggest that the two disorders share common pathogenic mechanism. MPTP/MPP+-induced neurodegeneration of dopaminergic neurons is a well characterized model which is therefore widely used to understand the pathogenesis of Parkinson's disease in a variety of primate and rodent models. 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 tetracycline, 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 “tetracycline” (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 tetracycline. You can also use this procedure to view pending patent applications concerning tetracycline. 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 TETRACYCLINE Overview This chapter provides bibliographic book references relating to tetracycline. In addition to online booksellers such as www.amazon.com and www.bn.com, excellent sources for book titles on tetracycline 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: Online Booksellers Commercial Internet-based booksellers, such as Amazon.com and Barnes&Noble.com, offer summaries which have been supplied by each title’s publisher. Some summaries also include customer reviews. Your local bookseller may have access to in-house and commercial databases that index all published books (e.g. Books in Print). IMPORTANT NOTE: Online booksellers typically produce search results for medical and non-medical books. When searching for “tetracycline” at online booksellers’ Web sites, you may discover non-medical books that use the generic term “tetracycline” (or a synonym) in their titles. The following is indicative of the results you might find when searching for “tetracycline” (sorted alphabetically by title; follow the hyperlink to view more details at Amazon.com): •
Encyclopedia of Chemical Technology: Vol.20: Tetracyclines to Unsaturated Polyesters by Raymond Eller Kirk, Frederick Othmer; ISBN: 0471484490; http://www.amazon.com/exec/obidos/ASIN/0471484490/icongroupinterna
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NTP technical report on the toxicology and carcinogenesis studies of tetracycline hydrochloride (CAS no. 64-75-5) in F344/N rats and B6C3F1 mice (feed studies) (SuDoc HE 20.3159/2:344) by U.S. Dept of Health and Human Services; ISBN: B0001030QK; http://www.amazon.com/exec/obidos/ASIN/B0001030QK/icongroupinterna
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Tetracycline manufacturing processes; ISBN: 0815502907; http://www.amazon.com/exec/obidos/ASIN/0815502907/icongroupinterna
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Tetracyclines in Biology, Chemistry and Medicine by W. Hillen (Editor), et al; ISBN: 3764362820; http://www.amazon.com/exec/obidos/ASIN/3764362820/icongroupinterna
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The Chemistry of the Tetracycline Antibiotics (Medicinal Research Series) by L.A. Mitscher; ISBN: 0824767160; http://www.amazon.com/exec/obidos/ASIN/0824767160/icongroupinterna
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The Tetracyclines (Handbook of Experimental Pharmacology, Vol 78) by J.J. Hlavka, J.H. Boothe (Editor); ISBN: 0387152598; http://www.amazon.com/exec/obidos/ASIN/0387152598/icongroupinterna
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The World Market for Tetracyclines, Derivatives, and Salts Thereof: A 2004 Global Trade Perspective [DOWNLOAD: PDF]; ISBN: B000134BR4; http://www.amazon.com/exec/obidos/ASIN/B000134BR4/icongroupinterna
Chapters on Tetracycline In order to find chapters that specifically relate to tetracycline, an excellent source of abstracts is the Combined Health Information Database. You will need to limit your search to book chapters and tetracycline 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 “tetracycline” (or synonyms) into the “For these words:” box. The following is a typical result when searching for book chapters on tetracycline: •
Antibiotics for Oral and Maxillofacial Infections Source: in Newman, M.G. and van Winkelhoff, A.J., eds. Antibiotic and Antimicrobial Use in Dental Practice. 2nd ed. Chicago, IL: Quintessence Publishing Co, Inc. 2001. p. 157-173. Contact: Available from Quintessence Publishing Co, Inc. 551 Kimberly Drive, Carol Stream, IL 60188-9981. (800) 621-0387 or (630) 682-3223. Fax (630) 682-3288. E-mail:
[email protected]. Website: www.quintpub.com. PRICE: $32.00 plus shipping and handling. ISBN: 0867153970. Summary: Infections of the oral and maxillofacial region, although commonly encountered by dentists, can be challenging to manage. This chapter on antibiotics for the treatment of oral and maxillofacial infections is from a textbook that integrates basic facts and principles of antibiotic therapy with recently-emerged concepts of care. The author presents guidelines for using a combination of antibiotics and surgery to manage minor orofacial and odontogenic (arising from the tissues that produce teeth) infections in the office setting. Topics include the microbiology of odontogenic infections; the natural course of odontogenic infections, i.e., cellulitis, abscess, and sinus tract; the spread of infection; the role of depressed host defenses, due to chemotherapy, metabolic diseases, organ transplants, or myeloproliferative diseases; and the use of dental spectrum antibiotics, including penicillin, extended spectrum penicillins, cephalosporins, erythromycin, clarithromycin, clindamycin, tetracycline, metronidazole, and fluoroquinolones. The author also reviews the principles of therapy, including determination of severity of the infection, evaluation of host defenses, surgical treatment, antibiotic choice, antibiotic administration, follow up, and side effects and secondary infection. The chapter concludes with a discussion of wound infection prophylaxis and special considerations, including sinus perforations, avulsed teeth, osteomyelitis, dry socket (alveolar osteitis), pericoronitis, routine extractions, and impacted third molars (wisdom teeth). Important principles, key facts, and clinical
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insights are highlighted and the chapter concludes with a list of references. 3 figures. 4 tables. 7 references. •
Fatty Liver (Macrosteatosis and Microsteatosis) Source: in Okuda, K., ed.,et al. Hepatobiliary Diseases: Pathophysiology and Imaging. Malden, MA: Blackwell Science, Inc. 2001. p. 152-168. Contact: Available from Blackwell Science, Inc. 350 Main Street, Commerce Place, Malden, MA 02148. (800) 215-1000 or (617) 388-8250. Fax (617) 388-8270. E-mail:
[email protected]. Website: www.blackwell-science.com. PRICE: $275.00. ISBN: 0632055421. Summary: Lipids (fats) make up about 20 percent of the liver mass, mostly in the form of phospholipids in membranes; neutral fat or triglycerides constitute less than 5 percent of the liver mass. This chapter on fatty liver is from a textbook that familiarizes the reader with various imaging modalities, the information they provide, and the merits of each, in order to facilitate the combined use of different imaging techniques in the diagnosis and management of hepatobiliary (liver and bile tract) diseases. Hepatocellular (liver cells) accumulation of fat results from increased delivery to the liver of dietary fat or fatty acids released from fat tissue, increased synthesis of fatty acids, reduced oxidation of fat, impaired export of triglycerides out of the liver, and excessive conversion of carbohydrate to fatty acids. The predominant contributing factor may be apparent with certain lifestyle and eating conditions, but in most cases it is difficult to determine. Steatosis (fatty liver) is easily diagnosed using ultrasound, CT scan, and MRI. The authors discuss classification, etiology and pathophysiology; macrosteatosis (nonalcoholic), including that due to obesity, diabetes mellitus, and hyperlipoprotinemias; microsteatosis, including acute fatty liver of pregnancy, Reye's syndrome, and that attributed to tetracycline; imaging strategies; the pathophysiology of focal sparing and focal fat deposits; distinguishing miscellaneous steatosis from liver tumor; and treatment, complications, and prognosis. 20 figures. 31 references.
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Considerations for Female Patients Source: in Newman, M.G. and van Winkelhoff, A.J., eds. Antibiotic and Antimicrobial Use in Dental Practice. 2nd ed. Chicago, IL: Quintessence Publishing Co, Inc. 2001. p. 235-242. Contact: Available from Quintessence Publishing Co, Inc. 551 Kimberly Drive, Carol Stream, IL 60188-9981. (800) 621-0387 or (630) 682-3223. Fax (630) 682-3288. E-mail:
[email protected]. Website: www.quintpub.com. PRICE: $32.00 plus shipping and handling. ISBN: 0867153970. Summary: This chapter discusses side effects and risks associated with the use of antibiotics and antimicrobials in women, with an emphasis on the effects of such treatment on pregnant and lactating women. The chapter is from a textbook that integrates basic facts and principles of antibiotic therapy with recently-emerged concepts of care. The author discusses considerations for antibiotic prescriptions, including vaginitis (a common side effect), and contraceptive failure; antibiotics that cross the placenta and reach the fetus; specific antibiotics and their effects in pregnant and lactating women, including penicillins, tetracycline, cephalosporins, erythromycin, clindamycin, metronidazole, azithromycin, aminoglycosides, sulfonamides, and chloramphenicol; periodontal considerations; and a final note on oral pain medications for pregnant or lactating women who are undergoing dental treatment. Important
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principles, key facts, and clinical insights are highlighted and the chapter concludes with a list of references. 1 figure. 2 tables. 33 references. •
Acquired and Developmental Disturbances of the Teeth and Associated Oral Structures Source: in McDonald, R.E. and Avery, D.A., eds. Dentistry for the Child and Adolescent. 7th ed. St. Louis, MO: Mosby, Inc. 2000. p. 105-150. Contact: Available from Harcourt Health Sciences. 11830 Westline Industrial Drive, St. Louis, MO 63146. (800) 325-4177. Fax (800) 874-6418. Website: www.harcourthealth.com. PRICE: $72.00 plus shipping and handling. ISBN: 0815190174. Summary: This chapter on acquired and developmental disturbances of the teeth and associated oral structures is from a textbook on dentistry for the child and adolescent that is designed to help undergraduate dental students and postdoctoral pediatric dentistry students provide comprehensive oral health care for infants, children, teenagers, and individuals with various disabilities. This chapter covers alveolar abscess; cellulitis (a diffuse infection of the soft tissues); developmental anomalies of the teeth, including odontoma (a tumor arising from a tooth germ), fusion of the teeth, germination, and dens in dente (dens invaginatus, tooth within a tooth); early exfoliation (shedding) of primary teeth, including that due to hypophosphatasia, familial fibrous dysplasia (cherubism), acrodynia, hypophosphatemia (rickets), cyclic neutropenia, and other disorders; enamel hypoplasia (less than normal growth of the enamel), including that due to nutritional deficiencies, to brain injury and neurologic defects, nephrotic syndrome, allergies, chronic pediatric lead poisoning, local infection and trauma, repaired cleft lip and palate, X radiation, rubella embryopathy, and fluoride (fluorosis); the use of enamel microabrasion to remove superficial enamel discolorations; preeruptive 'caries' (defects of the developing permanent teeth); inherited dentin defects, including dentinogenesis imperfecta and dentin dysplasia; amelogenesis imperfecta; enamel and dentin aplasia (lack of enamel and dentin); taurodontism; agenesis of teeth, including adontia (complete failure of the teeth to develop), hypodontia (oligodontia, a condition where only a few teeth develop), and ectodermal dysplasias; intrinsic discoloration of teeth, in erythroblastosois fetalis, porphyria, cystic fibrosis, tetracycline therapy, and their treatment with bleaching; micrognathia (small jaw); anomalies of the tongue, including macroglossia (large tongue), ankyloglossia (tongue tie), fissured tongue, geographic tongue, coated tongue, white strawberry tongue, black hairy tongue, indentation of the tongue margin (crenation), median rhomboid glossitis, and trauma to the tongue; and abnormal labial frenum and frenectomy. For each condition, the authors describe etiology, symptoms, diagnosis, and treatment options. 51 figures. 100 references.
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Teeth Disorders Source: in Scully, C. and Cawson, R.A. Oral Disease: Colour Guide. 2nd ed. Edinburgh, Scotland: Churchill Livingstone. 1999. p. 149-158. Contact: Available from W.B. Saunders Company, A Harcourt Health Sciences Company. Book Order Fulfillment Department, 11830 Westline Industrial Drive, St Louis, MO 63146-9988. (800) 545-2522. Fax (800) 568-5136. E-mail:
[email protected]. Website: www.wbsaunders.com. PRICE: $19.95 plus shipping and handling. ISBN: 044306170X. Summary: This chapter on teeth disorders is from a book that is intended as an aid to oral medicine and the diagnosis and treatment of oral disease. The chapter includes 11
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full color photographs of tooth disorders, with textual information accompanying them. Conditions covered are: ectodermal dysplasia, cleidocranial dysplasia, amelogenesis imperfecta, fluorosis, dentinogenesis imperfecta, tetracycline staining, erosion, and abrasion. For each condition, the text briefly covers incidence and etiology, clinical features, diagnosis and diagnostic tests, and treatment options. •
Topical Antimicrobial Agents: General Principles and Individual Drugs Source: in Newman, M.G. and van Winkelhoff, A.J., eds. Antibiotic and Antimicrobial Use in Dental Practice. 2nd ed. Chicago, IL: Quintessence Publishing Co, Inc. 2001. p. 5368. Contact: Available from Quintessence Publishing Co, Inc. 551 Kimberly Drive, Carol Stream, IL 60188-9981. (800) 621-0387 or (630) 682-3223. Fax (630) 682-3288. E-mail:
[email protected]. Website: www.quintpub.com. PRICE: $32.00 plus shipping and handling. ISBN: 0867153970. Summary: This chapter on topical antimicrobial agents for the treatment of periodontal disease is from a textbook that integrates basic facts and principles of antibiotic therapy with recently-emerged concepts of care. The authors focus on general principles for using topical antimicrobial agents, then discuss specific individual drugs. For the treatment of periodontal disease, antimicrobials can be delivered locally by means of pocket irrigation or placement of drug-containing ointments or gels or by using sophisticated devices for prolonged release of antibacterial agents. Specific agents discussed include two percent minocycline ointment, doxycycline hyclate in a biodegradable polymer, metronidazole gel, tetracycline in a nonresorbable plastic copolymer, and chlorhexidine gluconate in a gelatin chip. The authors discuss adverse reactions, a comparison of treatment methods and strategies, a comparison of local and systemic antibiotics, recolonization, and factors influencing the success of treatment. The authors conclude that to treat periodontal diseases successfully, local delivery devices must provide therapeutic levels of antimicrobial agents in the subgingival (under the gums) area over prolonged periods. Clinical trials demonstrate the efficacy of topical antimicrobial therapy under these conditions. Important principles, key facts, and clinical insights are highlighted and the chapter concludes with a list of references. 2 figures. 1 table. 76 references.
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Chapter 75: Perioral Dermatitis Source: in Freedberg, I.M., et al., eds. Fitzpatrick's Dermatology in General Medicine. 5th ed., Vol. 1. New York, NY: McGraw-Hill. 1999. p. 794-799. Contact: Available from McGraw-Hill Customer Services. P.O. Box 548, Blacklick, OH 43004-0548. (800) 262-4729 or (877) 833-5524. Fax (614) 759-3749 or (614) 759-3641. E-mail:
[email protected]. PRICE: $395.00 plus shipping and handling. ISBN: 0070219435. Summary: This chapter provides health professionals with information on the epidemiology, etiology, pathogenesis, clinical manifestations, diagnosis, treatment, and prevention of perioral dermatitis. This facial dermatosis predominantly affecting women of childbearing age is characterized by an erythematous, micropapular, fine scaling eruption classically affecting the nasolabial folds, chin, and upper lip. Factors implicated in causing perioral dermatitis include ultraviolet light, infective agents, demodectic infections, skin irritants, hormones, and glucocorticoids. Laboratory investigations that have been reported include patch testing, bacteriology, mycology for Candida, and a search for Demodex. Although diagnosis should be no problem in
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classic perioral dermatitis, when the clinical picture is not so distinctive, differential diagnosis should include rosacea, seborrheic dermatitis, contact dermatitis, acne, and papular sarcoid. Treatment involves the use of oral tetracycline. Prevention involves determining the cause, but many factors have been implicated in the etiology of perioral dermatitis, and none have been proven or confirmed. However, there is no doubt that the condition is precipitated or aggravated in many patients by using topical glucocorticoids. Untreated, the disease usually persists over several years, and the condition can resolve spontaneously. Prognosis is excellent with appropriate therapy. 3 figures and 72 references. •
Activated Charcoal Source: in Rational Use of Drugs In the Management of Acute Diarrhoea in Children. Geneva, Switzerland: World Health Organization. 1990. p. 59-63. Contact: Available from WHO Publications Center USA. 49 Sheridan Avenue, Albany, NY 12210. (518) 436-9686. Fax (518) 436-7433. PRICE: $12.60. ISBN: 9241561424. Order number 1150355. Summary: This chapter, from a guidebook detailing the use of drugs in the management of acute diarrhea in children, discusses activated charcoal. The authors discuss the formulations, pharmacology, mechanism of action, efficacy, and adverse effects of this agent. Although activated charcoal has been used empirically as an anti-diarrheal for many years, there is no clinical evidence that it shortens the duration of diarrhea, or that it reduces the number or volume of stools. Its action as an adsorbent causes it to bind other drugs including tetracycline, digestive enzymes, and intestinal micronutrients, which may be undesirable. The authors conclude that there is thus no rationale for the use of activated charcoal for the treatment of diarrhea in children. 19 references. (AAM).
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Helicobacter Pylori Infection, a Paradigm for Chronic Mucosal Inflammation: Pathogenesis and Implications for Eradication and Prevention Source: in Schrier, R.W., et al., eds. Advances in Internal Medicine. Vol 41. St. Louis, MO: Mosby-Year Book, Inc. 1996. p. 85-117. Contact: Available from Mosby Year-Book, Inc. 11830 Westline Industrial Drive, St. Louis, MO 63146. (800) 426-4545. Fax (800) 535-9935. E-mail:
[email protected]. PRICE: $72.95. ISBN: 0815183143. ISSN: 00652822. Summary: This chapter, from a yearbook of advances in internal medicine, covers the role of Helicobacter pylori infection in chronic mucosal inflammation, focusing on its pathogenesis and on implications for its eradication and prevention. After a brief section on the history of medical understanding of H. pylori, the authors discuss microbiology and epidemiology; clinical features, including acute infection, peptic ulcer disease, atrophic gastritis and gastric cancer, and gastric lymphoma; pathogenesis, including colonization of the gastric mucosa, gastric inflammation, characteristics of H. pylori strains associated with increased virulence, and microecologic perspectives; and treatment options, including the prospects for a vaccine. Four antibiotics to which H. pylori is susceptible in vivo are amoxicillin, tetracycline, clarithromycin, and metronidazole; bismuth salts are also included in many drug regimens. The authors conclude by reporting on animal studies on immunization against H. pylori. 3 figures. 3 tables. 214 references.
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CHAPTER 7. PERIODICALS AND NEWS ON TETRACYCLINE Overview In this chapter, we suggest a number of news sources and present various periodicals that cover tetracycline.
News Services and Press Releases One of the simplest ways of tracking press releases on tetracycline 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 “tetracycline” (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 tetracycline. 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 “tetracycline” (or synonyms). The following was recently listed in this archive for tetracycline: •
Tetracyclines could be an overlooked option for RA Source: Reuters Industry Breifing Date: October 31, 2003
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Tetracyclines may inhibit asthma-related IgE responses Source: Reuters Industry Breifing Date: September 05, 2002
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Tetracyclines have significant anti-prion activity Source: Reuters Industry Breifing Date: August 02, 2002
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Modified tetracyclines might slow progression of Parkinson's disease Source: Reuters Industry Breifing Date: November 26, 2001
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H. pylori resistant to metronidazole, tetracycline and amoxycillin Source: Reuters Medical News Date: August 11, 2000
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Tetracycline analog reverses Tet(B)-mediated tetracycline resistance Source: Reuters Medical News Date: July 13, 1999
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Bacterial infections treatable with tetracycline or quinolone may be linked to risk of MI Source: Reuters Medical News Date: February 03, 1999
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Tetracycline-resistant C trachomatis isolated in France may be new phenomenon Source: Reuters Medical News Date: August 21, 1998
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Tetracycline toxicity misdiagnosed as migraine Source: Reuters Medical News Date: July 07, 1998
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Bleomycin/Tetracycline Combination Best For Patients With Pleurodesis Source: Reuters Medical News Date: December 16, 1996 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
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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 “tetracycline” (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 “tetracycline” (or synonyms). If you know the name of a company that is relevant to tetracycline, 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 “tetracycline” (or synonyms).
Newsletter Articles Use the Combined Health Information Database, and limit your search criteria to “newsletter articles.” Again, you will need to use the “Detailed Search” option. Go directly to the following hyperlink: http://chid.nih.gov/detail/detail.html. Go to the bottom of the search page where “You may refine your search by.” Select the dates and language that you prefer. For the format option, select “Newsletter Article.” Type “tetracycline” (or synonyms) into the “For these words:” box. You should check back periodically with this database as it is updated every three months. The following is a typical result when searching for newsletter articles on tetracycline: •
Use of Antibiotics in Periodontal Therapy Source: Oral Care Report. 11(4): 5,8. 2001. Contact: Available from Oral Care Report. c/o Dr. Chester W. Douglass, Department of Oral Health Policy, Harvard School of Dental Medicine, 188 Longwood Avenue, Boston, MA 02115. Fax (617) 432-0047. E-mail:
[email protected]. Website: www.colgateprofessional.com (full-text available online). Summary: This brief report reviews the use of antibiotics in periodontal therapy. Treatment of periodontitis is based on four scientific principles: that bacteria cause the disease; the disease is chronic in nature; clinicians cannot remove all plaque and calculus on infected root surfaces; and the disease is recurrent and cannot be cured. Clinical research has shown that scaling and root planing (SRP) combined with systemic antibiotic administration was more effective than SRP alone in certain patient groups and with particular forms of periodontitis. This article summarizes the outcome of trials with either tetracycline, Augmentin, clindamycin, or metronidazole. The author also
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outlines the potential adverse effects of systemic antibiotics and the development of antibiotic resistance. The author notes that given the varied success of antibiotic treatment for periodontitis, together with the concerns regarding antibiotic resistance, local delivery of antimicrobials offers a new strategy in the treatment of adult periodontitis for certain patient subgroups that do not respond favorably to conventional therapy alone. Local delivery of antibiotics offers the advantages of direct access to the site of periodontitis, a therapeutic level that is above the minimum inhibitory concentration, and a minimal uptake of the drug into the systemic circulation, which reduces side effects and drug interactions. 1 figure. 3 references.
Academic Periodicals covering Tetracycline Numerous periodicals are currently indexed within the National Library of Medicine’s PubMed database that are known to publish articles relating to tetracycline. In addition to these sources, you can search for articles covering tetracycline 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 tetracycline. 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 tetracycline. 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 tetracycline: Bismuth Subsalicylate, Metronidazole, and Tetracycline—For H. pylori •
Systemic - U.S. Brands: Helidac http://www.nlm.nih.gov/medlineplus/druginfo/uspdi/203633.html
Doxycycline •
Dental - U.S. Brands: Atridox http://www.nlm.nih.gov/medlineplus/druginfo/uspdi/203716.html
Doxycycline For Dental Use •
Systemic - U.S. Brands: Periostat http://www.nlm.nih.gov/medlineplus/druginfo/uspdi/203724.html
Tetracycline Periodontal Fibers •
Dental - U.S. Brands: Actisite http://www.nlm.nih.gov/medlineplus/druginfo/uspdi/202729.html
Tetracyclines •
Systemic - U.S. Brands: Achromycin V; Declomycin; Doryx; Dynacin; Minocin; Monodox; Terramycin; Vibramycin; Vibra-Tabs http://www.nlm.nih.gov/medlineplus/druginfo/uspdi/202552.html
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Topical - U.S. Brands: Achromycin; Aureomycin; Meclan; Topicycline http://www.nlm.nih.gov/medlineplus/druginfo/uspdi/202553.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.
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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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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 Institute10: •
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/
10
These publications are typically written by one or more of the various NIH Institutes.
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National Institute on Alcohol Abuse and Alcoholism (NIAAA); guidelines available at http://www.niaaa.nih.gov/publications/publications.htm
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National Institute of Allergy and Infectious Diseases (NIAID); guidelines available at http://www.niaid.nih.gov/publications/
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National Institute of Arthritis and Musculoskeletal and Skin Diseases (NIAMS); fact sheets and guidelines available at http://www.niams.nih.gov/hi/index.htm
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National Institute of Child Health and Human Development (NICHD); guidelines available at http://www.nichd.nih.gov/publications/pubskey.cfm
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National Institute on Deafness and Other Communication Disorders (NIDCD); fact sheets and guidelines at http://www.nidcd.nih.gov/health/
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National Institute of Dental and Craniofacial Research (NIDCR); guidelines available at http://www.nidr.nih.gov/health/
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National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK); guidelines available at http://www.niddk.nih.gov/health/health.htm
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National Institute on Drug Abuse (NIDA); guidelines available at http://www.nida.nih.gov/DrugAbuse.html
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National Institute of Environmental Health Sciences (NIEHS); environmental health information available at http://www.niehs.nih.gov/external/facts.htm
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National Institute of Mental Health (NIMH); guidelines available at http://www.nimh.nih.gov/practitioners/index.cfm
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National Institute of Neurological Disorders and Stroke (NINDS); neurological disorder information pages available at http://www.ninds.nih.gov/health_and_medical/disorder_index.htm
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National Institute of Nursing Research (NINR); publications on selected illnesses at http://www.nih.gov/ninr/news-info/publications.html
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National Institute of Biomedical Imaging and Bioengineering; general information at http://grants.nih.gov/grants/becon/becon_info.htm
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Center for Information Technology (CIT); referrals to other agencies based on keyword searches available at http://kb.nih.gov/www_query_main.asp
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National Center for Complementary and Alternative Medicine (NCCAM); health information available at http://nccam.nih.gov/health/
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National Center for Research Resources (NCRR); various information directories available at http://www.ncrr.nih.gov/publications.asp
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Office of Rare Diseases; various fact sheets available at http://rarediseases.info.nih.gov/html/resources/rep_pubs.html
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Centers for Disease Control and Prevention; various fact sheets on infectious diseases available at http://www.cdc.gov/publications.htm
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NIH Databases In addition to the various Institutes of Health that publish professional guidelines, the NIH has designed a number of databases for professionals.11 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:12 •
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
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HIV/AIDS Resources: Describes various links and databases dedicated to HIV/AIDS research: http://www.nlm.nih.gov/pubs/factsheets/aidsinfs.html
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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
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Biotechnology Information: Access to public databases. The National Center for Biotechnology Information conducts research in computational biology, develops software tools for analyzing genome data, and disseminates biomedical information for the better understanding of molecular processes affecting human health and disease: http://www.ncbi.nlm.nih.gov/
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Population Information: The National Library of Medicine provides access to worldwide coverage of population, family planning, and related health issues, including family planning technology and programs, fertility, and population law and policy: http://www.nlm.nih.gov/databases/databases_population.html
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Cancer Information: Access to cancer-oriented databases: http://www.nlm.nih.gov/databases/databases_cancer.html
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Profiles in Science: Offering the archival collections of prominent twentieth-century biomedical scientists to the public through modern digital technology: http://www.profiles.nlm.nih.gov/
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Chemical Information: Provides links to various chemical databases and references: http://sis.nlm.nih.gov/Chem/ChemMain.html
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Clinical Alerts: Reports the release of findings from the NIH-funded clinical trials where such release could significantly affect morbidity and mortality: http://www.nlm.nih.gov/databases/alerts/clinical_alerts.html
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Space Life Sciences: Provides links and information to space-based research (including NASA): http://www.nlm.nih.gov/databases/databases_space.html
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MEDLINE: Bibliographic database covering the fields of medicine, nursing, dentistry, veterinary medicine, the healthcare system, and the pre-clinical sciences: http://www.nlm.nih.gov/databases/databases_medline.html
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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). 12 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
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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 Gateway13 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.14 To use the NLM Gateway, simply go to the search site at http://gateway.nlm.nih.gov/gw/Cmd. Type “tetracycline” (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 36893 128 975 277 254 38527
HSTAT15 HSTAT is a free, Web-based resource that provides access to full-text documents used in healthcare decision-making.16 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.17 Simply search by “tetracycline” (or synonyms) at the following Web site: http://text.nlm.nih.gov.
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Adapted from NLM: http://gateway.nlm.nih.gov/gw/Cmd?Overview.x.
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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). 15 Adapted from HSTAT: http://www.nlm.nih.gov/pubs/factsheets/hstat.html. 16 17
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 Biologists18 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.19 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.20 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/.
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Medical World Search: Searches full text from thousands of selected medical sites on the Internet; see http://www.mwsearch.com/.
18 Adapted 19
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. 20 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 tetracycline 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 tetracycline. 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 tetracycline. 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 “tetracycline”:
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Biodefense and Bioterrorism http://www.nlm.nih.gov/medlineplus/biodefenseandbioterrorism.html Cosmetic Dentistry http://www.nlm.nih.gov/medlineplus/cosmeticdentistry.html Plague http://www.nlm.nih.gov/medlineplus/plague.html Rosacea http://www.nlm.nih.gov/medlineplus/rosacea.html You may also choose to use the search utility provided by MEDLINEplus at the following Web address: http://www.nlm.nih.gov/medlineplus/. Simply type a keyword into the search box and click “Search.” This utility is similar to the NIH search utility, with the exception that it only includes materials that are linked within the MEDLINEplus system (mostly patient-oriented information). It also has the disadvantage of generating unstructured results. We recommend, therefore, that you use this method only if you have a very targeted search. The Combined Health Information Database (CHID) CHID Online is a reference tool that maintains a database directory of thousands of journal articles and patient education guidelines on tetracycline. CHID offers summaries that describe the guidelines available, including contact information and pricing. CHID’s general Web site is http://chid.nih.gov/. To search this database, go to http://chid.nih.gov/detail/detail.html. In particular, you can use the advanced search options to look up pamphlets, reports, brochures, and information kits. The following was recently posted in this archive: •
Tropical Sprue Source: New Fairfield, CT: National Organization for Rare Disorders Inc. 1999. 3 p. Contact: Available from National Organization for Rare Disorders (NORD). P.O. Box 1968, Danbury, CT 06813-1968. (800) 999-6673 or (203) 744-0100. Fax (203) 798-2291. TDD (203) 797-9590. E-mail:
[email protected]. Website: www.rarediseases.org. PRICE: $7.50. Summary: Malabsorption, multiple nutritional deficiencies, and abnormalities in the small bowel mucosa are the chief characteristics in Tropical Sprue, a disorder of unknown etiology. Symptoms include fatigue, diarrhea, anorexia, loss of weight, and general weakness. Treatment includes the use of folic acid and tetracycline. This document also contains a list of agencies to contact for further information.
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Rosacea: What You Should Know Source: Barrington, IL: National Rosacea Society. 2002. 16 p. Contact: Available from National Rosacea Society. 800 South Northwest Highway, Suite 200, Barrington, IL 60010. (888) 662-5874. E-mail:
[email protected]. Website: www.rosacea.org. PRICE: Single copy free. Summary: This booklet uses a question and answer format to provide people who have rosacea with information on this chronic disease affecting the skin of the face. Rosacea
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usually occurs in adults who are fair skinned and who have a history of flushing or blushing more easily and more often than the average person. Women are affected a little more often than men. Although the cause of rosacea is unknown, common triggers include hot drinks, alcohol, spicy foods, stress, sunlight, and extreme heat or cold. Symptoms include redness that resembles a blush or sunburn, pimples, thin red lines, and nasal bumps that make the nose look swollen (rhinophyma). In most people, symptoms come and go in cycles. Although rosacea may improve without treatment, it is often followed by a worsening of symptoms that progresses over time. Treatment involves use of topical or oral medications to control redness and reduce the number of papules and pustules. The most widely used topical antibacterial medication is metronidazole, and the most commonly used oral antibacterial medication is tetracycline. Successful treatment depends on understanding how much medication to use, how often to use it, how long to continue treatment, and how to use the medication correctly. Patients should follow a regular cleansing and medication routine to make treatment easier and more successful. Red lines can be covered up by makeup or removed surgically. Surgery can also be used to treat rhinophyma. Improvement depends on how far the disease had progressed when treatment started and how carefully the patient has followed treatment instructions. 5 figures. •
Helicobacter Pylori Source: Atlanta, GA: Centers for Disease Control and Prevention (CDC), Department of Health and Human Services. 199x. 4 p. Contact: Available from Centers for Disease Control and Prevention (CDC), Department of Health and Human Services. 1600 Clifton Road, NE, MS C09, Atlanta, GA 30333. (888) 698-5237. Website: www.cdc.gov/ncidod/dbmd/hpylori.htm. PRICE: Single copy free. Order number 995503. Summary: This fact sheet brings physicians up to date on the diagnosis and treatment of Helicobacter pylori infections. H. pylori is a spiral shaped bacterium that is found in the gastric mucus layer of the stomach and is thought to cause more than 90 percent of duodenal ulcers and more than 80 percent of gastric ulcers. The fact sheet lists common questions and answers, covering topics such as the incidence of H. pylori infection, the illnesses caused by the bacterium, ulcer symptoms, patient selection for testing and treatment for H. pylori, diagnostic tests, treatment regimens to eradicate H. pylori, long term consequences of infection, and current activities of the Centers for Disease Control and Prevention (CDC) in this area. Persons with active gastric or duodenal ulcers or documented history of ulcers should be tested for H. pylori, and if found to be infected, they should be treated. Testing for and treatment for H. pylori infection are also recommended after resection of early gastric cancer and for low grade gastric MALT lymphoma. Diagnostic tests used to determine H. pylori infection include serological (blood) tests, breath tests, and upper esophagogastroduodenal endoscopy. Therapy for H. pylori infection consists of 1 to 2 weeks of one or two effective antibiotics, such as amoxicillin, tetracycline, metronidazole, or clarithromycin, plus either ranitidine bismuth citrate, bismuth subsalicylate, or a proton pump inhibitor. The CDC has established an H. pylori information line for physicians and patients (888-MY-ULCER). Two other information resources are listed, the American Gastroenterological Association and the National Digestive Diseases Information Clearinghouse. 1 table. 3 references.
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Bullous Pemphigoid Source: Kirksville, MO: American Osteopathic College of Dermatology (AOCD). 2001. 2 p. Contact: Available online from American Osteopathic College of Dermatology. 1501 East Illinois Street, P.O. Box 7525, Kirksville, MO 63501. (800) 449-2623 or (660) 665-2184. Fax (660) 627-2623. E-mail:
[email protected]. Website: www.aocd.org/skin/dermatologic_diseases/ index.html. Summary: This fact sheet provides people who have bullous pemphigoid (BP) with information on this autoimmune disorder, which causes chronic skin blistering. Although the elderly are most often affected, the condition can occur at any age. Factors that have been reported to have a role in triggering BP include drugs, mechanical trauma, and physical trauma. The skin in BP is usually very itchy, and large red welts and hives may appear before or during the formation of blisters. These blisters are widespread and usually appear on parts of the body that flex. Diagnosis is confirmed by a skin biopsy. Treatment is aimed at relieving symptoms and preventing infection. Mild to moderate disease may be treated with tetracycline and minocycline. Severe cases are treated with oral steroids such as prednisone and prednisolone. Immunosuppressive agents such as Immuran, Cellcept, methotrexate, cyclophosphamide, and Neoral are used in combination with oral steroids. Although treatment is usually needed for several years, BP is a self limiting disease, so treatment can eventually be stopped. 2 figures.
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On the Way to a Cure Source: Atlanta, GA: Arthritis Foundation. 1998. 12 p. Contact: Available from Arthritis Foundation. P.O. Box 1616, Alpharetta, GA 300091616. (800) 207-8633. Fax (credit card orders only) (770) 442-9742. http://www.arthritis.org. PRICE: Single copy free from local Arthritis Foundation chapter (call 800-283-7800 for closest local chapter); bulk orders may be purchased from address above. Summary: This guide examines some of the latest advances in understanding and treating various forms of arthritis and related conditions. New treatment options for rheumatoid arthritis include a tetracycline derivative (minocycline), gentle nonsteroidal anti-inflammatory drugs (cyclooxygenase-2 inhibitors), and biologic agents (TNFR:Fc and inflixmab). Other options being investigated are manipulating genes, stopping the molecular actions that enable inflammatory cells to move into and anchor inside a joint, taking low doses of type II collagen, and inducing harmful cells to self-destruct. Possible new treatments for lupus include dehydroepiandrosterone, drugs for preserving kidney function, and daily vitamin supplements. Advances in understanding and treating juvenile rheumatoid arthritis focus on understanding genetic predisposition, using methotrexate, and identifying genetic markers. For ankylosing spondylitis, investigation centers on studying the genetics of the disease and the role of infectious processes. Advances in osteoarthritis focus on new surgical procedures to encourage cartilage to repair itself, drugs (doxycycline), and gene manipulation. With regard to Lyme disease, antibiotics and a possible vaccine are discussed. Further, the link between poor sleep and muscle damage and the role of chemical imbalances and emotional trauma in fibromyalgia are examined. Research on osteoporosis therapies, such as vitamin supplements, etidronate, and selective estrogen receptor modulators is also discussed.
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Gynecologic Problems: Pelvic Inflammatory Disease (PID) Contact: American College of Obstetricians and Gynecologists, PO Box 96920, Washington, DC, 20090-6920, (202) 638-5577, http://www.acog.com. Summary: This pamphlet addresses the causes, symptoms, diagnosis, and treatment of pelvic inflammatory disease (PID). Most cases of PID develop as a result of sexually transmitted diseases (STDs) such as gonorrhea and chlamydia. PID is normally treated with a combination of two or more antibiotics, such as ampicillin and tetracycline, to combat the wide variety of organisms associated with PID. The pamphlet recommends prevention strategies that include barrier contraception, spermicides, and limiting the number of sexual partners.
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Perioral Dermatitis Source: Schaumburg, IL: American Academy of Dermatology (AAD). 2000. 4 p. Contact: Available from American Academy of Dermatology, Marketing Department. P.O. Box 2289, Carol Stream, IL 60132-2289. (847) 240-1280. Fax (847) 240-1859. E-mail:
[email protected]. Website: www.aad.org. PRICE: Single copy free; bulk prices available. Summary: This pamphlet uses a question and answer format to provide people who have perioral dermatitis with information on the etiology, diagnosis, treatment, and prevention of this common skin problem that affects the area around the mouth. Although the problem mostly affects young women, occasionally men or children are affected. Features of this condition include redness of the skin around the mouth, small red bumps or pus bumps, and mild peeling. Although the cause of perioral dermatitis is unknown, some dermatologists believe it is a form of rosacea or seborrheic dermatitis worsened by sunlight. Use of strong corticosteroid creams can cause the condition, as can the use of some types of makeup, moisturizers, and dental products. Diagnosis is usually based on an examination of the skin. The most common treatment is an oral antibiotic such as tetracycline. Topical antibiotic creams may be used for milder cases or for pregnant women. Most patients improve after using oral antibiotics for 2 months, but stopping treatment too soon can cause a recurrence. There is no definitive way to prevent the condition. 2 figures. The National Guideline Clearinghouse™
The National Guideline Clearinghouse™ offers hundreds of evidence-based clinical practice guidelines published in the United States and other countries. You can search this site located at http://www.guideline.gov/ by using the keyword “tetracycline” (or synonyms). The following was recently posted: •
2002 national guideline for the management of Source: Association for Genitourinary Medicine - Medical Specialty Society; 1999 August (revised 2002); Various pagings http://www.guideline.gov/summary/summary.aspx?doc_id=3029&nbr=2255&a mp;string=tetracycline
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2002 national guideline for the management of donovanosis (granuloma inguinale) Source: Association for Genitourinary Medicine - Medical Specialty Society; 1999 August (revised 2002); Various pagings http://www.guideline.gov/summary/summary.aspx?doc_id=3038&nbr=2264&a mp;string=tetracycline
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2002 national guideline for the management of lymphogranuloma venereum Source: Association for Genitourinary Medicine - Medical Specialty Society; 1999 August (revised 2002); Various pagings http://www.guideline.gov/summary/summary.aspx?doc_id=3039&nbr=2265&a mp;string=tetracycline
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2002 national guideline for the management of prostatitis Source: Association for Genitourinary Medicine - Medical Specialty Society; 1999 August (revised 2002); Various pagings http://www.guideline.gov/summary/summary.aspx?doc_id=3041&nbr=2267&a mp;string=tetracycline
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2002 national guideline on the management of gonorrhoea in adults Source: Association for Genitourinary Medicine - Medical Specialty Society; 1999 August (revised 2002); Various pagings http://www.guideline.gov/summary/summary.aspx?doc_id=3031&nbr=2257&a mp;string=tetracycline
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2002 national guideline on the management of non-gonococcal urethritis Source: Association for Genitourinary Medicine - Medical Specialty Society; 1999 August (revised 2002); Various pagings http://www.guideline.gov/summary/summary.aspx?doc_id=3030&nbr=2256&a mp;string=tetracycline
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2002 national guidelines for the management of late syphilis Source: Association for Genitourinary Medicine - Medical Specialty Society; 1999 August (revised 2002); Various pagings http://www.guideline.gov/summary/summary.aspx?doc_id=3037&nbr=2263&a mp;string=tetracycline
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2002 national guidelines on the management of early syphilis Source: Association for Genitourinary Medicine - Medical Specialty Society; 1999 August (revised 2002); Various pagings http://www.guideline.gov/summary/summary.aspx?doc_id=3036&nbr=2262&a mp;string=tetracycline
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Acne Source: Finnish Medical Society Duodecim - Professional Association; 2001 April 30; Various pagings http://www.guideline.gov/summary/summary.aspx?doc_id=3389&nbr=2615&a mp;string=tetracycline
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Acute pharyngitis Source: Institute for Clinical Systems Improvement - Private Nonprofit Organization; 1998 August (revised 2003 May); 27 pages http://www.guideline.gov/summary/summary.aspx?doc_id=3873&nbr=3082&a mp;string=tetracycline
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American Association of Clinical Endocrinologists medical guidelines for clinical practice for the prevention and treatment of postmenopausal osteoporosis: 2001 edition, with selected updates for 2003 Source: American Association of Clinical Endocrinologists - Medical Specialty Society; 1996 Mar-April (updated 2003 Nov-Dec); 21 pages http://www.guideline.gov/summary/summary.aspx?doc_id=4157&nbr=3185&a mp;string=tetracycline
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American Gastroenterological Association medical position statement: celiac sprue Source: American Gastroenterological Association - Medical Specialty Society; 2000 November 12 (reviewed 2001); 4 pages http://www.guideline.gov/summary/summary.aspx?doc_id=3058&nbr=2284&a mp;string=tetracycline
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American Gastroenterological Association medical position statement: short bowel syndrome and intestinal transplantation Source: American Gastroenterological Association - Medical Specialty Society; 2003 April; 6 pages http://www.guideline.gov/summary/summary.aspx?doc_id=3795&nbr=3021&a mp;string=tetracycline
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Anthrax as a biological weapon, 2002: updated recommendations for management Source: Center for Civilian Biodefense Strategies, School of Medicine, Johns Hopkins University - Academic Institution; 1999 May 12 (updated 2002 May 1); 17 pages http://www.guideline.gov/summary/summary.aspx?doc_id=3220&nbr=2446&a mp;string=tetracycline
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Antibiotic prophylaxis in surgery. A national clinical guideline Source: Scottish Intercollegiate Guidelines Network - National Government Agency [Non-U.S.]; 2000 July; 36 pages http://www.guideline.gov/summary/summary.aspx?doc_id=2911&nbr=2137&a mp;string=tetracycline
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Care of the patient with ocular surface disorders Source: American Optometric Association - Professional Association; 1995 (revised 2002); 59 pages http://www.guideline.gov/summary/summary.aspx?doc_id=3549&nbr=2775&a mp;string=tetracycline
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Chlamydial urethritis and cervicitis Source: Finnish Medical Society Duodecim - Professional Association; 2001 June 5; Various pagings http://www.guideline.gov/summary/summary.aspx?doc_id=3401&nbr=2627&a mp;string=tetracycline
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Chronic obstructive pulmonary disease (COPD) Source: Finnish Medical Society Duodecim - Professional Association; 2002 April 27; Various pagings http://www.guideline.gov/summary/summary.aspx?doc_id=3399&nbr=2625&a mp;string=tetracycline
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Common gynecologic problems: a guide to diagnosis and treatment Source: Brigham and Women's Hospital (Boston) - Hospital/Medical Center; 2002; 11 pages http://www.guideline.gov/summary/summary.aspx?doc_id=3486&nbr=2712&a mp;string=tetracycline
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Community-acquired pneumonia in adults Source: Institute for Clinical Systems Improvement - Private Nonprofit Organization; 1999 August (revised 2002 May); 41 pages http://www.guideline.gov/summary/summary.aspx?doc_id=3351&nbr=2577&a mp;string=tetracycline
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Diagnosis and management of foodborne illnesses: a primer for physicians Source: American Medical Association - Medical Specialty Society; Reprint released 2001 January; 88 pages http://www.guideline.gov/summary/summary.aspx?doc_id=2707&nbr=1933&a mp;string=tetracycline
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Diseases characterized by genital ulcers. Sexually transmitted diseases treatment guidelines 2002 Source: Centers for Disease Control and Prevention - Federal Government Agency [U.S.]; 1993 (revised 2002 May 10); 25 pages http://www.guideline.gov/summary/summary.aspx?doc_id=3233&nbr=2459&a mp;string=tetracycline
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Diseases characterized by urethritis and cervicitis. Sexually transmitted diseases treatment guidelines 2002 Source: Centers for Disease Control and Prevention - Federal Government Agency [U.S.]; 1993 (revised 2002 May 10); 13 pages http://www.guideline.gov/summary/summary.aspx?doc_id=3236&nbr=2462&a mp;string=tetracycline
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Dyspepsia Source: Institute for Clinical Systems Improvement - Private Nonprofit Organization; 1998 October (revised 2003 Jan); 48 pages http://www.guideline.gov/summary/summary.aspx?doc_id=3664&nbr=2890&a mp;string=tetracycline
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Epididymitis. Sexually transmitted diseases treatment guidelines 2002 Source: Centers for Disease Control and Prevention - Federal Government Agency [U.S.]; 1993 (revised 2002 May 10); 2 pages http://www.guideline.gov/summary/summary.aspx?doc_id=3239&nbr=2465&a mp;string=tetracycline
•
Evidence base for management of acute exacerbations of chronic obstructive pulmonary disease Source: American College of Chest Physicians - Medical Specialty Society; 2001 April 3; 5 pages http://www.guideline.gov/summary/summary.aspx?doc_id=2762&nbr=1988&a mp;string=tetracycline
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Helicobacter pylori infection in children: recommendations for diagnosis and treatment Source: North American Society for Pediatric Gastroenterology, Hepatology, and Nutrition - Professional Association; 2000 November; 8 pages http://www.guideline.gov/summary/summary.aspx?doc_id=3594&nbr=2820&a mp;string=tetracycline
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Management of genital Source: Scottish Intercollegiate Guidelines Network - National Government Agency [Non-U.S.]; 2000 March; 26 pages http://www.guideline.gov/summary/summary.aspx?doc_id=2304&nbr=1530&a mp;string=tetracycline
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Pelvic inflammatory disease. Sexually transmitted diseases treatment guidelines 2002 Source: Centers for Disease Control and Prevention - Federal Government Agency [U.S.]; 1993 (revised 2002 May 10); 5 pages http://www.guideline.gov/summary/summary.aspx?doc_id=3238&nbr=2464&a mp;string=tetracycline
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Peptic ulcer disease Source: University of Michigan Health System - Academic Institution; 1996 October (revised 1999 May); 6 pages http://www.guideline.gov/summary/summary.aspx?doc_id=2286&nbr=1512&a mp;string=tetracycline
•
Plague as a biological weapon. Medical and public health management Source: Center for Civilian Biodefense Strategies, School of Medicine, Johns Hopkins University - Academic Institution; 2000 October 4; 10 pages http://www.guideline.gov/summary/summary.aspx?doc_id=2983&nbr=2209&a mp;string=tetracycline
•
Practice guidelines for the management of community-acquired pneumonia in adults Source: Infectious Diseases Society of America - Medical Specialty Society; 2000 February; 36 pages http://www.guideline.gov/summary/summary.aspx?doc_id=2665&nbr=1891&a mp;string=tetracycline
•
Practice management guidelines for prophylactic antibiotic use in penetrating abdominal trauma Source: Eastern Association for the Surgery of Trauma - Professional Association; 2000; 33 pages http://www.guideline.gov/summary/summary.aspx?doc_id=2677&nbr=1903&a mp;string=tetracycline
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Practice management guidelines for prophylactic antibiotic use in tube thoracostomy for traumatic hemopneumothorax Source: Eastern Association for the Surgery of Trauma - Professional Association; 2000; 16 pages http://www.guideline.gov/summary/summary.aspx?doc_id=2678&nbr=1904&a mp;string=tetracycline
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Proctitis, proctocolitis, and enteritis. Sexually transmitted diseases treatment guidelines 2002 Source: Centers for Disease Control and Prevention - Federal Government Agency [U.S.]; 1993 (revised 2002 May 10); 2 pages http://www.guideline.gov/summary/summary.aspx?doc_id=3244&nbr=2470&a mp;string=tetracycline
•
Recommendations for using smallpox vaccine in a pre-event smallpox vaccination program. Supplemental recommendations of the Advisory Committee on Immunization Practices (ACIP) and the Healthcare Infection Control Practices Advisory Committee (HICPAC). Source: Centers for Disease Control and Prevention - Federal Government Agency [U.S.]; 2003 February 26; 17 pages http://www.guideline.gov/summary/summary.aspx?doc_id=3623&nbr=2849&a mp;string=tetracycline
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Use of anthrax vaccine in the United States. Recommendations of the Advisory Committee on Immunization Practices Source: Centers for Disease Control and Prevention - Federal Government Agency [U.S.]; 2000 December 15; 21 pages http://www.guideline.gov/summary/summary.aspx?doc_id=2652&nbr=1878&a mp;string=tetracycline
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Use of antibiotics in adults Source: Singapore Ministry of Health - National Government Agency [Non-U.S.]; 2000 April; 78 pages http://www.guideline.gov/summary/summary.aspx?doc_id=3434&nbr=2660&a mp;string=tetracycline
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Use of antibiotics in paediatric care Source: Singapore Ministry of Health - National Government Agency [Non-U.S.]; 2002 March; 109 pages http://www.guideline.gov/summary/summary.aspx?doc_id=3436&nbr=2662&a mp;string=tetracycline
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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 tetracycline. 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
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Family Village: http://www.familyvillage.wisc.edu/specific.htm
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Google: http://directory.google.com/Top/Health/Conditions_and_Diseases/
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Med Help International: http://www.medhelp.org/HealthTopics/A.html
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Open Directory Project: http://dmoz.org/Health/Conditions_and_Diseases/
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Yahoo.com: http://dir.yahoo.com/Health/Diseases_and_Conditions/
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WebMDHealth: http://my.webmd.com/health_topics
Finding Associations There are several Internet directories that provide lists of medical associations with information on or resources relating to tetracycline. By consulting all of associations listed in this chapter, you will have nearly exhausted all sources for patient associations concerned with tetracycline. 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 tetracycline. 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
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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 “tetracycline” (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 “tetracycline”. 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 “tetracycline” (or synonyms) into the “For these words:” box. You should check back periodically with this database since it is updated every three months. The National Organization for Rare Disorders, Inc. The National Organization for Rare Disorders, Inc. has prepared a Web site that provides, at no charge, lists of associations organized by health topic. You can access this database at the following Web site: http://www.rarediseases.org/search/orgsearch.html. Type “tetracycline” (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.21
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
21
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)22: •
Alabama: Health InfoNet of Jefferson County (Jefferson County Library Cooperative, Lister Hill Library of the Health Sciences), http://www.uab.edu/infonet/
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Alabama: Richard M. Scrushy Library (American Sports Medicine Institute)
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Arizona: Samaritan Regional Medical Center: The Learning Center (Samaritan Health System, Phoenix, Arizona), http://www.samaritan.edu/library/bannerlibs.htm
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California: Kris Kelly Health Information Center (St. Joseph Health System, Humboldt), http://www.humboldt1.com/~kkhic/index.html
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California: Community Health Library of Los Gatos, http://www.healthlib.org/orgresources.html
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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
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California: Gateway Health Library (Sutter Gould Medical Foundation)
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California: Health Library (Stanford University Medical Center), http://wwwmed.stanford.edu/healthlibrary/
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California: Patient Education Resource Center - Health Information and Resources (University of California, San Francisco), http://sfghdean.ucsf.edu/barnett/PERC/default.asp
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California: Redwood Health Library (Petaluma Health Care District), http://www.phcd.org/rdwdlib.html
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California: Los Gatos PlaneTree Health Library, http://planetreesanjose.org/
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California: Sutter Resource Library (Sutter Hospitals Foundation, Sacramento), http://suttermedicalcenter.org/library/
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California: Health Sciences Libraries (University of California, Davis), http://www.lib.ucdavis.edu/healthsci/
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California: ValleyCare Health Library & Ryan Comer Cancer Resource Center (ValleyCare Health System, Pleasanton), http://gaelnet.stmarysca.edu/other.libs/gbal/east/vchl.html
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California: Washington Community Health Resource Library (Fremont), http://www.healthlibrary.org/
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Colorado: William V. Gervasini Memorial Library (Exempla Healthcare), http://www.saintjosephdenver.org/yourhealth/libraries/
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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/
22
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
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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
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Delaware: Lewis B. Flinn Library (Delaware Academy of Medicine, Wilmington), http://www.delamed.org/chls.html
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Georgia: Family Resource Library (Medical College of Georgia, Augusta), http://cmc.mcg.edu/kids_families/fam_resources/fam_res_lib/frl.htm
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Georgia: Health Resource Center (Medical Center of Central Georgia, Macon), http://www.mccg.org/hrc/hrchome.asp
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Hawaii: Hawaii Medical Library: Consumer Health Information Service (Hawaii Medical Library, Honolulu), http://hml.org/CHIS/
•
Idaho: DeArmond Consumer Health Library (Kootenai Medical Center, Coeur d’Alene), http://www.nicon.org/DeArmond/index.htm
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Illinois: Health Learning Center of Northwestern Memorial Hospital (Chicago), http://www.nmh.org/health_info/hlc.html
•
Illinois: Medical Library (OSF Saint Francis Medical Center, Peoria), http://www.osfsaintfrancis.org/general/library/
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Kentucky: Medical Library - Services for Patients, Families, Students & the Public (Central Baptist Hospital, Lexington), http://www.centralbap.com/education/community/library.cfm
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Kentucky: University of Kentucky - Health Information Library (Chandler Medical Center, Lexington), http://www.mc.uky.edu/PatientEd/
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Louisiana: Alton Ochsner Medical Foundation Library (Alton Ochsner Medical Foundation, New Orleans), http://www.ochsner.org/library/
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Louisiana: Louisiana State University Health Sciences Center Medical LibraryShreveport, http://lib-sh.lsuhsc.edu/
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Maine: Franklin Memorial Hospital Medical Library (Franklin Memorial Hospital, Farmington), http://www.fchn.org/fmh/lib.htm
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Maine: Gerrish-True Health Sciences Library (Central Maine Medical Center, Lewiston), http://www.cmmc.org/library/library.html
•
Maine: Hadley Parrot Health Science Library (Eastern Maine Healthcare, Bangor), http://www.emh.org/hll/hpl/guide.htm
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Maine: Maine Medical Center Library (Maine Medical Center, Portland), http://www.mmc.org/library/
•
Maine: Parkview Hospital (Brunswick), http://www.parkviewhospital.org/
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Maine: Southern Maine Medical Center Health Sciences Library (Southern Maine Medical Center, Biddeford), http://www.smmc.org/services/service.php3?choice=10
•
Maine: Stephens Memorial Hospital’s Health Information Library (Western Maine Health, Norway), http://www.wmhcc.org/Library/
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Manitoba, Canada: Consumer & Patient Health Information Service (University of Manitoba Libraries), http://www.umanitoba.ca/libraries/units/health/reference/chis.html
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Manitoba, Canada: J.W. Crane Memorial Library (Deer Lodge Centre, Winnipeg), http://www.deerlodge.mb.ca/crane_library/about.asp
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Maryland: Health Information Center at the Wheaton Regional Library (Montgomery County, Dept. of Public Libraries, Wheaton Regional Library), http://www.mont.lib.md.us/healthinfo/hic.asp
•
Massachusetts: Baystate Medical Center Library (Baystate Health System), http://www.baystatehealth.com/1024/
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Massachusetts: Boston University Medical Center Alumni Medical Library (Boston University Medical Center), http://med-libwww.bu.edu/library/lib.html
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Massachusetts: Lowell General Hospital Health Sciences Library (Lowell General Hospital, Lowell), http://www.lowellgeneral.org/library/HomePageLinks/WWW.htm
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Massachusetts: Paul E. Woodard Health Sciences Library (New England Baptist Hospital, Boston), http://www.nebh.org/health_lib.asp
•
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/
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Michigan: Botsford General Hospital Library - Consumer Health (Botsford General Hospital, Library & Internet Services), http://www.botsfordlibrary.org/consumer.htm
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Michigan: Helen DeRoy Medical Library (Providence Hospital and Medical Centers), http://www.providence-hospital.org/library/
•
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
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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
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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
265
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
267
TETRACYCLINE DICTIONARY The definitions below are derived from official public sources, including the National Institutes of Health [NIH] and the European Union [EU]. 1-Methyl-4-phenylpyridinium: 1-Methyl-4-phenylpyridinium (MPP+). An active neurotoxic metabolite of 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP). The compound reduces dopamine levels, inhibits the biosynthesis of catecholamines, depletes cardiac norepinephrine and inactivates tyrosine hydroxylase. These and other toxic effects lead to cessation of oxidative phosphorylation, ATP depletion, and cell death. The compound, which is related to paraquat, has also been used as an herbicide. [NIH] Abdomen: That portion of the body that lies between the thorax and the pelvis. [NIH] Abdominal: Having to do with the abdomen, which is the part of the body between the chest and the hips that contains the pancreas, stomach, intestines, liver, gallbladder, and other organs. [NIH] Aberrant: Wandering or deviating from the usual or normal course. [EU] Ablate: In surgery, is to remove. [NIH] Ablation: The removal of an organ by surgery. [NIH] Abortion: 1. The premature expulsion from the uterus of the products of conception - of the embryo, or of a nonviable fetus. The four classic symptoms, usually present in each type of abortion, are uterine contractions, uterine haemorrhage, softening and dilatation of the cervix, and presentation or expulsion of all or part of the products of conception. 2. Premature stoppage of a natural or a pathological process. [EU] Abrasion: 1. The wearing away of a substance or structure (such as the skin or the teeth) through some unusual or abnormal mechanical process. 2. An area of body surface denuded of skin or mucous membrane by some unusual or abnormal mechanical process. [EU] Abscess: A localized, circumscribed collection of pus. [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] Acceptor: A substance which, while normally not oxidized by oxygen or reduced by hydrogen, can be oxidized or reduced in presence of a substance which is itself undergoing oxidation or reduction. [NIH] Acetaminophen: Analgesic antipyretic derivative of acetanilide. It has weak antiinflammatory properties and is used as a common analgesic, but may cause liver, blood cell, and kidney damage. [NIH] Acetylcholine: A neurotransmitter. Acetylcholine in vertebrates is the major transmitter at neuromuscular junctions, autonomic ganglia, parasympathetic effector junctions, a subset of sympathetic effector junctions, and at many sites in the central nervous system. It is generally not used as an administered drug because it is broken down very rapidly by cholinesterases, but it is useful in some ophthalmological applications. [NIH] Acetylgalactosamine: The N-acetyl derivative of galactosamine. [NIH] Acetylglucosamine: The N-acetyl derivative of glucosamine. [NIH] Acidity: The quality of being acid or sour; containing acid (hydrogen ions). [EU]
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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 Rosacea: An acneiform eruption occurring mostly in middle-aged adults and appearing generally on the forehead, cheeks, nose, and chin. Three types are recognized: granulomatous, glandular hyperplastic with rhinophyma, and ocular. [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] Acremonium: A mitosporic fungal genus with many reported ascomycetous teleomorphs. Cephalosporin antibiotics are derived from this genus. [NIH] Acrodermatitis: Inflammation involving the skin of the extremities, especially the hands and feet. Several forms are known, some idiopathic and some hereditary. The infantile form is called Gianotti-Crosti syndrome. [NIH] Acrodynia: A condition occurring in infants, marked by swollen, bluish red hands and feet and disordered digestion, followed by multiple arthritis and muscular weakness. [NIH] Actin: Essential component of the cell skeleton. [NIH] Actinin: A protein factor that regulates the length of R-actin. It is chemically similar, but immunochemically distinguishable from actin. [NIH] Actinomycosis: Infections with bacteria of the genus Actinomyces. [NIH] Acute leukemia: A rapidly progressing cancer of the blood-forming tissue (bone marrow). [NIH]
Acute lymphoblastic leukemia: ALL. A quickly progressing disease in which too many immature white blood cells called lymphoblasts are found in the blood and bone marrow. Also called acute lymphocytic leukemia. [NIH] Acute lymphocytic leukemia: ALL. A quickly progressing disease in which too many immature white blood cells called lymphoblasts are found in the blood and bone marrow. Also called acute lymphoblastic leukemia. [NIH] Acute myelogenous leukemia: AML. A quickly progressing disease in which too many immature blood-forming cells are found in the blood and bone marrow. Also called acute myeloid leukemia or acute nonlymphocytic leukemia. [NIH] Acute myeloid leukemia: AML. A quickly progressing disease in which too many immature blood-forming cells are found in the blood and bone marrow. Also called acute myelogenous leukemia or acute nonlymphocytic leukemia. [NIH] Acute nonlymphocytic leukemia: A quickly progressing disease in which too many immature blood-forming cells are found in the blood and bone marrow. Also called acute myeloid leukemia or acute myelogenous leukemia. [NIH] Acyl: Chemical signal used by bacteria to communicate. [NIH] Acyl Carrier Protein: Consists of a polypeptide chain and 4'-phosphopantetheine linked to a serine residue by a phosphodiester bond. Acyl groups are bound as thiol esters to the pantothenyl group. Acyl carrier protein is involved in every step of fatty acid synthesis by the cytoplasmic system. [NIH] Adaptability: Ability to develop some form of tolerance to conditions extremely different from those under which a living organism evolved. [NIH]
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Adaptation: 1. The adjustment of an organism to its environment, or the process by which it enhances such fitness. 2. The normal ability of the eye to adjust itself to variations in the intensity of light; the adjustment to such variations. 3. The decline in the frequency of firing of a neuron, particularly of a receptor, under conditions of constant stimulation. 4. In dentistry, (a) the proper fitting of a denture, (b) the degree of proximity and interlocking of restorative material to a tooth preparation, (c) the exact adjustment of bands to teeth. 5. In microbiology, the adjustment of bacterial physiology to a new environment. [EU] Adenine: A purine base and a fundamental unit of adenine nucleotides. [NIH] Adenocarcinomas: A malignant tumor of the epithelial cells of a gland which typically metastasizes by way of the lymphatics. [NIH] Adenoma: A benign epithelial tumor with a glandular organization. [NIH] Adenovirus: A group of viruses that cause respiratory tract and eye infections. Adenoviruses used in gene therapy are altered to carry a specific tumor-fighting gene. [NIH] Adenylate Cyclase: An enzyme of the lyase class that catalyzes the formation of cyclic AMP and pyrophosphate from ATP. EC 4.6.1.1. [NIH] Adhesives: Substances that cause the adherence of two surfaces. They include glues (properly collagen-derived adhesives), mucilages, sticky pastes, gums, resins, or latex. [NIH] Adipocytes: Fat-storing cells found mostly in the abdominal cavity and subcutaneous tissue. Fat is usually stored in the form of tryglycerides. [NIH] Adipose Tissue: Connective tissue composed of fat cells lodged in the meshes of areolar tissue. [NIH] Adjustment: The dynamic process wherein the thoughts, feelings, behavior, and biophysiological mechanisms of the individual continually change to adjust to the environment. [NIH] Adjuvant: A substance which aids another, such as an auxiliary remedy; in immunology, nonspecific stimulator (e.g., BCG vaccine) of the immune response. [EU] Adoptive Transfer: Form of passive immunization where previously sensitized immunologic agents (cells or serum) are transferred to non-immune recipients. When transfer of cells is used as a therapy for the treatment of neoplasms, it is called adoptive immunotherapy (immunotherapy, adoptive). [NIH] Adrenal Cortex: The outer layer of the adrenal gland. It secretes mineralocorticoids, androgens, and glucocorticoids. [NIH] Adrenergic: Activated by, characteristic of, or secreting epinephrine or substances with similar activity; the term is applied to those nerve fibres that liberate norepinephrine at a synapse when a nerve impulse passes, i.e., the sympathetic fibres. [EU] Adsorption: The condensation of gases, liquids, or dissolved substances on the surfaces of solids. It includes adsorptive phenomena of bacteria and viruses as well as of tissues treated with exogenous drugs and chemicals. [NIH] Adsorptive: It captures volatile compounds by binding them to agents such as activated carbon or adsorptive resins. [NIH] Adverse Effect: An unwanted side effect of treatment. [NIH] Aerobic: In biochemistry, reactions that need oxygen to happen or happen when oxygen is present. [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,
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organ, or structure. 3. Chemical affinity; the force that binds atoms in molecules; the tendency of substances to combine by chemical reaction. 4. The strength of noncovalent chemical binding between two substances as measured by the dissociation constant of the complex. 5. In immunology, a thermodynamic expression of the strength of interaction between a single antigen-binding site and a single antigenic determinant (and thus of the stereochemical compatibility between them), most accurately applied to interactions among simple, uniform antigenic determinants such as haptens. Expressed as the association constant (K litres mole -1), which, owing to the heterogeneity of affinities in a population of antibody molecules of a given specificity, actually represents an average value (mean intrinsic association constant). 6. The reciprocal of the dissociation constant. [EU] Affinity Chromatography: In affinity chromatography, a ligand attached to a column binds specifically to the molecule to be purified. [NIH] Agar: A complex sulfated polymer of galactose units, extracted from Gelidium cartilagineum, Gracilaria confervoides, and related red algae. It is used as a gel in the preparation of solid culture media for microorganisms, as a bulk laxative, in making emulsions, and as a supporting medium for immunodiffusion and immunoelectrophoresis. [NIH]
Age Groups: Persons classified by age from birth (infant, newborn) to octogenarians and older (aged, 80 and over). [NIH] Aged, 80 and Over: A person 80 years of age and older. [NIH] Agenesis: Lack of complete or normal development; congenital absence of an organ or part. [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] Albumin: 1. Any protein that is soluble in water and moderately concentrated salt solutions and is coagulable by heat. 2. Serum albumin; the major plasma protein (approximately 60 per cent of the total), which is responsible for much of the plasma colloidal osmotic pressure and serves as a transport protein carrying large organic anions, such as fatty acids, bilirubin, and many drugs, and also carrying certain hormones, such as cortisol and thyroxine, when their specific binding globulins are saturated. Albumin is synthesized in the liver. Low serum levels occur in protein malnutrition, active inflammation and serious hepatic and renal disease. [EU] Aldehydes: Organic compounds containing a carbonyl group in the form -CHO. [NIH] Algorithms: A procedure consisting of a sequence of algebraic formulas and/or logical steps to calculate or determine a given task. [NIH] Alimentary: Pertaining to food or nutritive material, or to the organs of digestion. [EU] Alkaline: Having the reactions of an alkali. [EU] Alkaloid: A member of a large group of chemicals that are made by plants and have nitrogen in them. Some alkaloids have been shown to work against cancer. [NIH] Alleles: Mutually exclusive forms of the same gene, occupying the same locus on homologous chromosomes, and governing the same biochemical and developmental process. [NIH] Allograft: An organ or tissue transplant between two humans. [NIH] Allopurinol: A xanthine oxidase inhibitor that decreases uric acid production. [NIH] Alloys: A mixture of metallic elements or compounds with other metallic or metalloid elements in varying proportions. [NIH]
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Alopecia: Absence of hair from areas where it is normally present. [NIH] Alpha Particles: Positively charged particles composed of two protons and two neutrons, i.e., helium nuclei, emitted during disintegration of very heavy isotopes; a beam of alpha particles or an alpha ray has very strong ionizing power, but weak penetrability. [NIH] Alternative medicine: Practices not generally recognized by the medical community as standard or conventional medical approaches and used instead of standard treatments. Alternative medicine includes the taking of dietary supplements, megadose vitamins, and herbal preparations; the drinking of special teas; and practices such as massage therapy, magnet therapy, spiritual healing, and meditation. [NIH] Aluminum: A metallic element that has the atomic number 13, atomic symbol Al, and atomic weight 26.98. [NIH] Alveolitis: Inflammation of an alveolus. Called also odontobothritis. [EU] Amaurosis: Partial or total blindness from any cause. [NIH] Amebiasis: Infection with any of various amebae. It is an asymptomatic carrier state in most individuals, but diseases ranging from chronic, mild diarrhea to fulminant dysentery may occur. [NIH] Ameliorating: A changeable condition which prevents the consequence of a failure or accident from becoming as bad as it otherwise would. [NIH] Amelogenesis Imperfecta: Either hereditary enamel hypoplasia or hypocalcification. [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: Any organic compound containing an amino (-NH2 and a carboxyl (- COOH) group. The 20 a-amino acids listed in the accompanying table are the amino acids from which proteins are synthesized by formation of peptide bonds during ribosomal translation of messenger RNA; all except glycine, which is not optically active, have the L configuration. Other amino acids occurring in proteins, such as hydroxyproline in collagen, are formed by posttranslational enzymatic modification of amino acids residues in polypeptide chains. There are also several important amino acids, such as the neurotransmitter y-aminobutyric acid, that have no relation to proteins. Abbreviated AA. [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-terminal: The end of a protein or polypeptide chain that contains a free amino group (-NH2). [NIH] Ammonia: A colorless alkaline gas. It is formed in the body during decomposition of organic materials during a large number of metabolically important reactions. [NIH] Amoxicillin: A broad-spectrum semisynthetic antibiotic similar to ampicillin except that its resistance to gastric acid permits higher serum levels with oral administration. [NIH] Ampicillin: Semi-synthetic derivative of penicillin that functions as an orally active broadspectrum antibiotic. [NIH] Amplification: The production of additional copies of a chromosomal DNA sequence, found as either intrachromosomal or extrachromosomal DNA. [NIH]
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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] Anabolic: Relating to, characterized by, or promoting anabolism. [EU] Anaemia: A reduction below normal in the number of erythrocytes per cu. mm., in the quantity of haemoglobin, or in the volume of packed red cells per 100 ml. of blood which occurs when the equilibrium between blood loss (through bleeding or destruction) and blood production is disturbed. [EU] Anaerobic: 1. Lacking molecular oxygen. 2. Growing, living, or occurring in the absence of molecular oxygen; pertaining to an anaerobe. [EU] Anaesthesia: Loss of feeling or sensation. Although the term is used for loss of tactile sensibility, or of any of the other senses, it is applied especially to loss of the sensation of pain, as it is induced to permit performance of surgery or other painful procedures. [EU] 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] 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] Anaplasia: Loss of structural differentiation and useful function of neoplastic cells. [NIH] Anaplasmosis: A disease of cattle caused by parasitization of the red blood cells by bacteria of the genus Anaplasma. [NIH] Anatomical: Pertaining to anatomy, or to the structure of the organism. [EU] Anchorage: In dentistry, points of retention of fillings and artificial restorations and appliances. [NIH] Androgens: A class of sex hormones associated with the development and maintenance of the secondary male sex characteristics, sperm induction, and sexual differentiation. In addition to increasing virility and libido, they also increase nitrogen and water retention and stimulate skeletal growth. [NIH] Anemia: A reduction in the number of circulating erythrocytes or in the quantity of hemoglobin. [NIH] Aneurysm: A sac formed by the dilatation of the wall of an artery, a vein, or the heart. [NIH] Angina: Chest pain that originates in the heart. [NIH] Angina Pectoris: The symptom of paroxysmal pain consequent to myocardial ischemia usually of distinctive character, location and radiation, and provoked by a transient stressful situation during which the oxygen requirements of the myocardium exceed the capacity of the coronary circulation to supply it. [NIH] Anginal: Pertaining to or characteristic of angina. [EU] Angiogenesis: Blood vessel formation. Tumor angiogenesis is the growth of blood vessels
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from surrounding tissue to a solid tumor. This is caused by the release of chemicals by the tumor. [NIH] Angiogenesis inhibitor: A substance that may prevent the formation of blood vessels. In anticancer therapy, an angiogenesis inhibitor prevents the growth of blood vessels from surrounding tissue to a solid tumor. [NIH] Angiography: Radiography of blood vessels after injection of a contrast medium. [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] Angiotensinogen: An alpha-globulin of which a fragment of 14 amino acids is converted by renin to angiotensin I, the inactive precursor of angiotensin II. It is a member of the serpin superfamily. [NIH] Animal model: An animal with a disease either the same as or like a disease in humans. Animal models are used to study the development and progression of diseases and to test new treatments before they are given to humans. Animals with transplanted human cancers or other tissues are called xenograft models. [NIH] Anionic: Pertaining to or containing an anion. [EU] Anions: Negatively charged atoms, radicals or groups of atoms which travel to the anode or positive pole during electrolysis. [NIH] Annealing: The spontaneous alignment of two single DNA strands to form a double helix. [NIH]
Anomalies: Birth defects; abnormalities. [NIH] Anorexia: Lack or loss of appetite for food. Appetite is psychologic, dependent on memory and associations. Anorexia can be brought about by unattractive food, surroundings, or company. [NIH] Anterior chamber: The space in front of the iris and behind the cornea. [NIH] Anthrax: An acute bacterial infection caused by ingestion of bacillus organisms. Carnivores may become infected from ingestion of infected carcasses. It is transmitted to humans by contact with infected animals or contaminated animal products. The most common form in humans is cutaneous anthrax. [NIH] Antiandrogens: Drugs used to block the production or interfere with the action of male sex hormones. [NIH] Antibacterial: A substance that destroys bacteria or suppresses their growth or reproduction. [EU] Antibiotic: A drug used to treat infections caused by bacteria and other microorganisms. [NIH]
Antibiotics, Aminoglycoside: Antibiotics whose structure contains amino sugars attached to an aminocyclitol ring (hexose nucleus) by glycosidic bonds. Aminoglycoside antibiotics are derived from various species of Streptomyces and Micromonospora or are produced synthetically. They act by inhibiting protein synthesis. [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
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binding is to help destroy the antigen. Antibodies can work in several ways, depending on the nature of the antigen. Some antibodies destroy antigens directly. Others make it easier for white blood cells to destroy the antigen. [NIH] Anticoagulant: A drug that helps prevent blood clots from forming. Also called a blood thinner. [NIH] Antifungal: Destructive to fungi, or suppressing their reproduction or growth; effective against fungal infections. [EU] Antifungal Agents: Substances that destroy fungi by suppressing their ability to grow or reproduce. They differ from fungicides, industrial because they defend against fungi present in human or animal tissues. [NIH] Antigen: Any substance which is capable, under appropriate conditions, of inducing a specific immune response and of reacting with the products of that response, that is, with specific antibody or specifically sensitized T-lymphocytes, or both. Antigens may be soluble substances, such as toxins and foreign proteins, or particulate, such as bacteria and tissue cells; however, only the portion of the protein or polysaccharide molecule known as the antigenic determinant (q.v.) combines with antibody or a specific receptor on a lymphocyte. Abbreviated Ag. [EU] Antigen-Antibody Complex: The complex formed by the binding of antigen and antibody molecules. The deposition of large antigen-antibody complexes leading to tissue damage causes immune complex diseases. [NIH] Antigen-presenting cell: APC. A cell that shows antigen on its surface to other cells of the immune system. This is an important part of an immune response. [NIH] Antihypertensive: An agent that reduces high blood pressure. [EU] 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] Antineoplastic: Inhibiting or preventing the development of neoplasms, checking the maturation and proliferation of malignant cells. [EU] Antioxidant: A substance that prevents damage caused by free radicals. Free radicals are highly reactive chemicals that often contain oxygen. They are produced when molecules are split to give products that have unpaired electrons. This process is called oxidation. [NIH] Antiphlogistic: An agent that counteracts inflammation and fever. [EU] Antipsychotic: Effective in the treatment of psychosis. Antipsychotic drugs (called also neuroleptic drugs and major tranquilizers) are a chemically diverse (including phenothiazines, thioxanthenes, butyrophenones, dibenzoxazepines, dibenzodiazepines, and diphenylbutylpiperidines) but pharmacologically similar class of drugs used to treat schizophrenic, paranoid, schizoaffective, and other psychotic disorders; acute delirium and dementia, and manic episodes (during induction of lithium therapy); to control the movement disorders associated with Huntington's chorea, Gilles de la Tourette's syndrome, and ballismus; and to treat intractable hiccups and severe nausea and vomiting. Antipsychotic agents bind to dopamine, histamine, muscarinic cholinergic, a-adrenergic, and serotonin receptors. Blockade of dopaminergic transmission in various areas is thought to be responsible for their major effects : antipsychotic action by blockade in the mesolimbic
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and mesocortical areas; extrapyramidal side effects (dystonia, akathisia, parkinsonism, and tardive dyskinesia) by blockade in the basal ganglia; and antiemetic effects by blockade in the chemoreceptor trigger zone of the medulla. Sedation and autonomic side effects (orthostatic hypotension, blurred vision, dry mouth, nasal congestion and constipation) are caused by blockade of histamine, cholinergic, and adrenergic receptors. [EU] Antipyretic: An agent that relieves or reduces fever. Called also antifebrile, antithermic and febrifuge. [EU] Antiseptic: A substance that inhibits the growth and development of microorganisms without necessarily killing them. [EU] Antiviral: Destroying viruses or suppressing their replication. [EU] Anus: The opening of the rectum to the outside of the body. [NIH] Anxiety: Persistent feeling of dread, apprehension, and impending disaster. [NIH] Aorta: The main trunk of the systemic arteries. [NIH] Aortic Aneurysm: Aneurysm of the aorta. [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] Apoptosis: One of the two mechanisms by which cell death occurs (the other being the pathological process of necrosis). Apoptosis is the mechanism responsible for the physiological deletion of cells and appears to be intrinsically programmed. It is characterized by distinctive morphologic changes in the nucleus and cytoplasm, chromatin cleavage at regularly spaced sites, and the endonucleolytic cleavage of genomic DNA (DNA fragmentation) at internucleosomal sites. This mode of cell death serves as a balance to mitosis in regulating the size of animal tissues and in mediating pathologic processes associated with tumor growth. [NIH] Aqueous: Having to do with water. [NIH] Arachidonic Acid: An unsaturated, essential fatty acid. It is found in animal and human fat as well as in the liver, brain, and glandular organs, and is a constituent of animal phosphatides. It is formed by the synthesis from dietary linoleic acid and is a precursor in the biosynthesis of prostaglandins, thromboxanes, and leukotrienes. [NIH] Archaea: One of the three domains of life (the others being bacteria and Eucarya), formerly called Archaebacteria under the taxon Bacteria, but now considered separate and distinct. They are characterized by: 1) the presence of characteristic tRNAs and ribosomal RNAs; 2) the absence of peptidoglycan cell walls; 3) the presence of ether-linked lipids built from branched-chain subunits; and 4) their occurrence in unusual habitats. While archaea resemble bacteria in morphology and genomic organization, they resemble eukarya in their method of genomic replication. The domain contains at least three kingdoms: crenarchaeota, euryarchaeota, and korarchaeota. [NIH] Arginine: An essential amino acid that is physiologically active in the L-form. [NIH] Aromatic: Having a spicy odour. [EU] Arterial: Pertaining to an artery or to the arteries. [EU] Arteries: The vessels carrying blood away from the heart. [NIH] Arterioles: The smallest divisions of the arteries located between the muscular arteries and the capillaries. [NIH]
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Arteriosus: Circle composed of anastomosing arteries derived from two long posterior ciliary and seven anterior ciliary arteries, located in the ciliary body about the root of the iris. [NIH]
Artery: Vessel-carrying blood from the heart to various parts of the body. [NIH] Articular: Of or pertaining to a joint. [EU] 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] Aseptic: Free from infection or septic material; sterile. [EU] Aspartate: A synthetic amino acid. [NIH] Aspergillosis: Infections with fungi of the genus Aspergillus. [NIH] Aspirin: A drug that reduces pain, fever, inflammation, and blood clotting. Aspirin belongs to the family of drugs called nonsteroidal anti-inflammatory agents. It is also being studied in cancer prevention. [NIH] Assay: Determination of the amount of a particular constituent of a mixture, or of the biological or pharmacological potency of a drug. [EU] Astringents: Agents, usually topical, that cause the contraction of tissues for the control of bleeding or secretions. [NIH] Astrocytes: The largest and most numerous neuroglial cells in the brain and spinal cord. Astrocytes (from "star" cells) are irregularly shaped with many long processes, including 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] Atrial: Pertaining to an atrium. [EU] Atrial Fibrillation: Disorder of cardiac rhythm characterized by rapid, irregular atrial impulses and ineffective atrial contractions. [NIH] Atrioventricular: Pertaining to an atrium of the heart and to a ventricle. [EU] Atrium: A chamber; used in anatomical nomenclature to designate a chamber affording entrance to another structure or organ. Usually used alone to designate an atrium of the heart. [EU] Atrophic Gastritis: Chronic irritation of the stomach lining. Causes the stomach lining and glands to wither away. [NIH] Atrophy: Decrease in the size of a cell, tissue, organ, or multiple organs, associated with a variety of pathological conditions such as abnormal cellular changes, ischemia, malnutrition, or hormonal changes. [NIH] Attenuated: Strain with weakened or reduced virulence. [NIH] Auditory: Pertaining to the sense of hearing. [EU] Autacoids: A chemically diverse group of substances produced by various tissues in the body that cause slow contraction of smooth muscle; they have other intense but varied
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pharmacologic activities. [NIH] Autodigestion: Autolysis; a condition found in disease of the stomach: the stomach wall is digested by the gastric juice. [NIH] Autoimmune disease: A condition in which the body recognizes its own tissues as foreign and directs an immune response against them. [NIH] Autonomic: Self-controlling; functionally independent. [EU] Axons: Nerve fibers that are capable of rapidly conducting impulses away from the neuron cell body. [NIH] Azithromycin: A semi-synthetic macrolide antibiotic structurally related to erythromycin. It has been used in the treatment of Mycobacterium avium intracellulare infections, toxoplasmosis, and cryptosporidiosis. [NIH] Babesiosis: A group of tick-borne diseases of mammals including zoonoses in humans. They are caused by protozoans of the genus babesia, which parasitize erythrocytes, producing hemolysis. In the U.S., the organism's natural host is mice and transmission is by the deer tick ixodes scapularis. [NIH] Bacillus: A genus of Bacillaceae that are spore-forming, rod-shaped cells. Most species are saprophytic soil forms with only a few species being pathogenic. [NIH] Bacteraemia: The presence of bacteria in the blood. [EU] Bacteria: Unicellular prokaryotic microorganisms which generally possess rigid cell walls, multiply by cell division, and exhibit three principal forms: round or coccal, rodlike or bacillary, and spiral or spirochetal. [NIH] Bacterial Infections: Infections by bacteria, general or unspecified. [NIH] Bacterial Physiology: Physiological processes and activities of bacteria. [NIH] Bacterial Proteins: Proteins found in any species of bacterium. [NIH] Bactericidal: Substance lethal to bacteria; substance capable of killing bacteria. [NIH] Bacteriophage: A virus whose host is a bacterial cell; A virus that exclusively infects bacteria. It generally has a protein coat surrounding the genome (DNA or RNA). One of the coliphages most extensively studied is the lambda phage, which is also one of the most important. [NIH] Bacteriophage lambda: A temperate inducible phage and type species of the genus lambdalike Phages, in the family Siphoviridae. Its natural host is E. coli K12. Its virion contains linear double-stranded DNA, except for 12 complementary bases at the 5'-termini of the polynucleotide chains. The DNA circularizes on infection. [NIH] Bacteriostatic: 1. Inhibiting the growth or multiplication of bacteria. 2. An agent that inhibits the growth or multiplication of bacteria. [EU] Bacterium: Microscopic organism which may have a spherical, rod-like, or spiral unicellular or non-cellular body. Bacteria usually reproduce through asexual processes. [NIH] Barium: An element of the alkaline earth group of metals. It has an atomic symbol Ba, atomic number 56, and atomic weight 138. All of its acid-soluble salts are poisonous. [NIH] Base: In chemistry, the nonacid part of a salt; a substance that combines with acids to form salts; a substance that dissociates to give hydroxide ions in aqueous solutions; a substance whose molecule or ion can combine with a proton (hydrogen ion); a substance capable of donating a pair of electrons (to an acid) for the formation of a coordinate covalent bond. [EU] Base Sequence: The sequence of purines and pyrimidines in nucleic acids and polynucleotides. It is also called nucleotide or nucleoside sequence. [NIH]
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Basement Membrane: Ubiquitous supportive tissue adjacent to epithelium and around smooth and striated muscle cells. This tissue contains intrinsic macromolecular components such as collagen, laminin, and sulfated proteoglycans. As seen by light microscopy one of its subdivisions is the basal (basement) lamina. [NIH] Basophils: Granular leukocytes characterized by a relatively pale-staining, lobate nucleus and cytoplasm containing coarse dark-staining granules of variable size and stainable by basic dyes. [NIH] Benign: Not cancerous; does not invade nearby tissue or spread to other parts of the body. [NIH]
Benzene: Toxic, volatile, flammable liquid hydrocarbon biproduct of coal distillation. It is used as an industrial solvent in paints, varnishes, lacquer thinners, gasoline, etc. Benzene causes central nervous system damage acutely and bone marrow damage chronically and is carcinogenic. It was formerly used as parasiticide. [NIH] Benzoic Acid: A fungistatic compound that is widely used as a food preservative. It is conjugated to glycine in the liver and excreted as hippuric acid. [NIH] Beta-Galactosidase: A group of enzymes that catalyzes the hydrolysis of terminal, nonreducing beta-D-galactose residues in beta-galactosides. Deficiency of beta-Galactosidase A1 may cause gangliodisosis GM1. EC 3.2.1.23. [NIH] Beta-Lactamases: Enzymes found in many bacteria which catalyze the hydrolysis of the amide bond in the beta-lactam ring. Well known antibiotics destroyed by these enzymes are penicillins and cephalosporins. EC 3.5.2.6. [NIH] 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] Biliary: Having to do with the liver, bile ducts, and/or gallbladder. [NIH] Biliary Tract: The gallbladder and its ducts. [NIH] Bilirubin: A bile pigment that is a degradation product of heme. [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] 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] Biological response modifier: BRM. A substance that stimulates the body's response to infection and disease. [NIH]
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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] Bioluminescence: The emission of light by living organisms such as the firefly, certain mollusks, beetles, fish, bacteria, fungi and protozoa. [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] Bioreactors: Tools or devices for generating products using the synthetic or chemical conversion capacity of a biological system. They can be classical fermentors, cell culture perfusion systems, or enzyme bioreactors. For production of proteins or enzymes, recombinant microorganisms such as bacteria, mammalian cells, or insect or plant cells are usually chosen. [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] Bismuth: A metallic element that has the atomic symbol Bi, atomic number 83 and atomic weight 208.98. [NIH] Bismuth Subsalicylate: A nonprescription medicine such as Pepto-Bismol. Used to treat diarrhea, heartburn, indigestion, and nausea. It is also part of the treatment for ulcers caused by the bacterium Helicobacter pylori (HELL-uh-koh-BAK-tur py-LOH-ree). [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] Blastocyst: The mammalian embryo in the post-morula stage in which a fluid-filled cavity, enclosed primarily by trophoblast, contains an inner cell mass which becomes the embryonic disc. [NIH] Blastomyces: A genus of onygenacetous mitosporic fungi whose perfect state is Ajellomyces. The species Blastomyces dermatitidis (perfect state Ajellomyces dermatitidis) causes blastomycosis. [NIH] Blastomycosis: A fungal infection that may appear in two forms: 1) a primary lesion characterized by the formation of a small cutaneous nodule and small nodules along the lymphatics that may heal within several months; and 2) chronic granulomatous lesions characterized by thick crusts, warty growths, and unusual vascularity and infection in the middle or upper lobes of the lung. [NIH] Blennorrhoea: A general term including any inflammatory process of the external eye which
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gives a mucoid discharge, more exactly, a discharge of mucus. [NIH] Bleomycin: A complex of related glycopeptide antibiotics from Streptomyces verticillus consisting of bleomycin A2 and B2. It inhibits DNA metabolism and is used as an antineoplastic, especially for solid tumors. [NIH] Blepharitis: Inflammation of the eyelids. [NIH] Blister: Visible accumulations of fluid within or beneath the epidermis. [NIH] Blood Coagulation: The process of the interaction of blood coagulation factors that results in an insoluble fibrin clot. [NIH] Blood Glucose: Glucose in blood. [NIH] Blood Platelets: Non-nucleated disk-shaped cells formed in the megakaryocyte and found in the blood of all mammals. They are mainly involved in blood coagulation. [NIH] Blood pressure: The pressure of blood against the walls of a blood vessel or heart chamber. Unless there is reference to another location, such as the pulmonary artery or one of the heart chambers, it refers to the pressure in the systemic arteries, as measured, for example, in the forearm. [NIH] Blood vessel: A tube in the body through which blood circulates. Blood vessels include a network of arteries, arterioles, capillaries, venules, and veins. [NIH] Blood-Brain Barrier: Specialized non-fenestrated tightly-joined endothelial cells (tight junctions) that form a transport barrier for certain substances between the cerebral capillaries and the brain tissue. [NIH] Blot: To transfer DNA, RNA, or proteins to an immobilizing matrix such as nitrocellulose. [NIH]
Blotting, Western: Identification of proteins or peptides that have been electrophoretically separated by blotting and transferred to strips of nitrocellulose paper. The blots are then detected by radiolabeled antibody probes. [NIH] Blushing: Involuntary reddening, especially of the face, associated with feelings of embarrassment, confusion, or shame. [NIH] Body Burden: The total amount of a chemical, metal or radioactive substance present at any time after absorption in the body of man or animal. [NIH] Body Fluids: Liquid components of living organisms. [NIH] Bone Density: The amount of mineral per square centimeter of bone. This is the definition used in clinical practice. Actual bone density would be expressed in grams per milliliter. It is most frequently measured by photon absorptiometry or x-ray computed tomography. [NIH] Bone Marrow: The soft tissue filling the cavities of bones. Bone marrow exists in two types, yellow and red. Yellow marrow is found in the large cavities of large bones and consists mostly of fat cells and a few primitive blood cells. Red marrow is a hematopoietic tissue and is the site of production of erythrocytes and granular leukocytes. Bone marrow is made up of a framework of connective tissue containing branching fibers with the frame being filled with marrow cells. [NIH] Bone Marrow Transplantation: The transference of bone marrow from one human or animal to another. [NIH] Bone Resorption: Bone loss due to osteoclastic activity. [NIH] Bowel: The long tube-shaped organ in the abdomen that completes the process of digestion. There is both a small and a large bowel. Also called the intestine. [NIH] Bowel Movement: Body wastes passed through the rectum and anus. [NIH]
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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] Bradykinin: A nonapeptide messenger that is enzymatically produced from kallidin in the blood where it is a potent but short-lived agent of arteriolar dilation and increased capillary permeability. Bradykinin is also released from mast cells during asthma attacks, from gut walls as a gastrointestinal vasodilator, from damaged tissues as a pain signal, and may be a neurotransmitter. [NIH] Brain 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] Brain Stem: The part of the brain that connects the cerebral hemispheres with the spinal cord. It consists of the mesencephalon, pons, and medulla oblongata. [NIH] Branch: Most commonly used for branches of nerves, but applied also to other structures. [NIH]
Breakdown: A physical, metal, or nervous collapse. [NIH] Breath Tests: Any tests done on exhaled air. [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] 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] Bronchitis: Inflammation (swelling and reddening) of the bronchi. [NIH] Bronchopulmonary: Pertaining to the lungs and their air passages; both bronchial and pulmonary. [EU] Bronchopulmonary Dysplasia: A chronic lung disease appearing in certain newborn infants treated for respiratory distress syndrome with mechanical ventilation and elevated concentration of inspired oxygen. [NIH] Brucellosis: Infection caused by bacteria of the genus Brucella mainly involving the reticuloendothelial system. This condition is characterized by fever, weakness, malaise, and weight loss. [NIH] Buccal: Pertaining to or directed toward the cheek. In dental anatomy, used to refer to the buccal surface of a tooth. [EU] Bullous: Pertaining to or characterized by bullae. [EU] Bupivacaine: A widely used local anesthetic agent. [NIH] Burns: Injuries to tissues caused by contact with heat, steam, chemicals (burns, chemical), electricity (burns, electric), or the like. [NIH] Burns, Electric: Burns produced by contact with electric current or from a sudden discharge of electricity. [NIH] Butyric Acid: A four carbon acid, CH3CH2CH2COOH, with an unpleasant odor that occurs
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in butter and animal fat as the glycerol ester. [NIH] Bypass: A surgical procedure in which the doctor creates a new pathway for the flow of body fluids. [NIH] Cachexia: General ill health, malnutrition, and weight loss, usually associated with chronic disease. [NIH] Cadherins: A group of functionally related glycoproteins responsible for the calciumdependent cell-to-cell adhesion mechanism. They are divided into subclasses E-, P-, and Ncadherins, which are distinct in immunological specificity and tissue distribution. They promote cell adhesion via a homophilic mechanism. These compounds play a role in the construction of tissues and of the whole animal body. [NIH] Cadmium: An element with atomic symbol Cd, atomic number 48, and atomic weight 114. It is a metal and ingestion will lead to cadmium poisoning. [NIH] Cadmium Poisoning: Poisoning occurring after exposure to cadmium compounds or fumes. It may cause gastrointestinal syndromes, anemia, or pneumonitis. [NIH] Calcification: Deposits of calcium in the tissues of the breast. Calcification in the breast can be seen on a mammogram, but cannot be detected by touch. There are two types of breast calcification, macrocalcification and microcalcification. Macrocalcifications are large deposits and are usually not related to cancer. Microcalcifications are specks of calcium that may be found in an area of rapidly dividing cells. Many microcalcifications clustered together may be a sign of cancer. [NIH] Calcium: A basic element found in nearly all organized tissues. It is a member of the alkaline earth family of metals with the atomic symbol Ca, atomic number 20, and atomic weight 40. Calcium is the most abundant mineral in the body and combines with phosphorus to form calcium phosphate in the bones and teeth. It is essential for the normal functioning of nerves and muscles and plays a role in blood coagulation (as factor IV) and in many enzymatic processes. [NIH] Calcium Hydroxide: Ca(OH)2. A white powder that has many therapeutic uses. Because of its ability to stimulate mineralization, it is found in many dental formulations. [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] Calmodulin: A heat-stable, low-molecular-weight activator protein found mainly in the brain and heart. The binding of calcium ions to this protein allows this protein to bind to cyclic nucleotide phosphodiesterases and to adenyl cyclase with subsequent activation. Thereby this protein modulates cyclic AMP and cyclic GMP levels. [NIH] Candidiasis: Infection with a fungus of the genus Candida. It is usually a superficial infection of the moist cutaneous areas of the body, and is generally caused by C. albicans; it most commonly involves the skin (dermatocandidiasis), oral mucous membranes (thrush, def. 1), respiratory tract (bronchocandidiasis), and vagina (vaginitis). Rarely there is a systemic infection or endocarditis. Called also moniliasis, candidosis, oidiomycosis, and formerly blastodendriosis. [EU] Candidosis: An infection caused by an opportunistic yeasts that tends to proliferate and become pathologic when the environment is favorable and the host resistance is weakened. [NIH]
Cannula: A tube for insertion into a duct or cavity; during insertion its lumen is usually occupied by a trocar. [EU] 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
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interchange of various substances, including fluids, between the blood and tissue fluid; called also vas capillare. [EU] Capillary Permeability: Property of blood capillary walls that allows for the selective exchange of substances. Small lipid-soluble molecules such as carbon dioxide and oxygen move freely by diffusion. Water and water-soluble molecules cannot pass through the endothelial walls and are dependent on microscopic pores. These pores show narrow areas (tight junctions) which may limit large molecule movement. [NIH] Capping: A 7-methyl guanosine cap attached to the 5'-end of eucaryotic mRNAs by a phosphodiester linkage. The cap is believed to increase the stability of the message, since most nucleases require a 5'-3'or 3'-5'bond in order to cleave the RNA. [NIH] Capsid: The outer protein protective shell of a virus, which protects the viral nucleic acid. [NIH]
Capsules: Hard or soft soluble containers used for the oral administration of medicine. [NIH] Captopril: A potent and specific inhibitor of peptidyl-dipeptidase A. It blocks the conversion of angiotensin I to angiotensin II, a vasoconstrictor and important regulator of arterial blood pressure. Captopril acts to suppress the renin-angiotensin system and inhibits pressure responses to exogenous angiotensin. [NIH] Carbohydrate: An aldehyde or ketone derivative of a polyhydric alcohol, particularly of the pentahydric and hexahydric alcohols. They are so named because the hydrogen and oxygen are usually in the proportion to form water, (CH2O)n. The most important carbohydrates are the starches, sugars, celluloses, and gums. They are classified into mono-, di-, tri-, polyand heterosaccharides. [EU] Carbon Dioxide: A colorless, odorless gas that can be formed by the body and is necessary for the respiration cycle of plants and animals. [NIH] Carboxy: Cannabinoid. [NIH] Carboxylic Acids: Organic compounds containing the carboxy group (-COOH). This group of compounds includes amino acids and fatty acids. Carboxylic acids can be saturated, unsaturated, or aromatic. [NIH] Carcinogen: Any substance that causes cancer. [NIH] Carcinogenesis: The process by which normal cells are transformed into cancer cells. [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] Cardiac arrest: A sudden stop of heart function. [NIH] Cardiomyopathy: A general diagnostic term designating primary myocardial disease, often of obscure or unknown etiology. [EU] Cardioselective: Having greater activity on heart tissue than on other tissue. [EU] 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] Carotid Arteries: Either of the two principal arteries on both sides of the neck that supply blood to the head and neck; each divides into two branches, the internal carotid artery and the external carotid artery. [NIH] Case report: A detailed report of the diagnosis, treatment, and follow-up of an individual
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patient. Case reports also contain some demographic information about the patient (for example, age, gender, ethnic origin). [NIH] Caspase: Enzyme released by the cell at a crucial stage in apoptosis in order to shred all cellular proteins. [NIH] Cataract: An opacity, partial or complete, of one or both eyes, on or in the lens or capsule, especially an opacity impairing vision or causing blindness. The many kinds of cataract are classified by their morphology (size, shape, location) or etiology (cause and time of occurrence). [EU] Catecholamine: A group of chemical substances manufactured by the adrenal medulla and secreted during physiological stress. [NIH] Catfish: Common name to express the order Siluriformes. This order contains many families and over 2,000 species, including venomous species. Heteropneustes and Plotosus genera have dangerous stings and are aggressive. Most species are passive stingers. [NIH] Catheter: A flexible tube used to deliver fluids into or withdraw fluids from the body. [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] Cathode: An electrode, usually an incandescent filament of tungsten, which emits electrons in an X-ray tube. [NIH] Cations: Postively charged atoms, radicals or groups of atoms which travel to the cathode or negative pole during electrolysis. [NIH] Caudal: Denoting a position more toward the cauda, or tail, than some specified point of reference; same as inferior, in human anatomy. [EU] Causality: The relating of causes to the effects they produce. Causes are termed necessary when they must always precede an effect and sufficient when they initiate or produce an effect. Any of several factors may be associated with the potential disease causation or outcome, including predisposing factors, enabling factors, precipitating factors, reinforcing factors, and risk factors. [NIH] Cause of Death: Factors which produce cessation of all vital bodily functions. They can be analyzed from an epidemiologic viewpoint. [NIH] Cefixime: A third-generation cephalosporin antibiotic that is stable to hydrolysis by betalactamases. [NIH] Cefotaxime: Semisynthetic broad-spectrum cephalosporin. [NIH] Ceftazidime: Semisynthetic, broad-spectrum antibacterial derived from cephaloridine and used especially for Pseudomonas and other gram-negative infections in debilitated patients. [NIH]
Ceftriaxone: Broad-spectrum cephalosporin antibiotic with a very long half-life and high penetrability to usually inaccessible infections, including those involving the meninges, eyes, inner ears, and urinary tract. [NIH] Celiac Disease: A disease characterized by intestinal malabsorption and precipitated by gluten-containing foods. The intestinal mucosa shows loss of villous structure. [NIH] Cell: The individual unit that makes up all of the tissues of the body. All living things are made up of one or more cells. [NIH] Cell Adhesion: Adherence of cells to surfaces or to other cells. [NIH] Cell Adhesion Molecules: Surface ligands, usually glycoproteins, that mediate cell-to-cell
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adhesion. Their functions include the assembly and interconnection of various vertebrate systems, as well as maintenance of tissue integration, wound healing, morphogenic movements, cellular migrations, and metastasis. [NIH] Cell Aggregation: The phenomenon by which dissociated cells intermixed in vitro tend to group themselves with cells of their own type. [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 Lineage: The developmental history of cells as traced from the first division of the original cell or cells in the embryo. [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 motility: The ability of a cell to move. [NIH] Cell Physiology: Characteristics and physiological processes of cells from cell division to cell death. [NIH] Cell proliferation: An increase in the number of cells as a result of cell growth and cell division. [NIH] Cell Respiration: The metabolic process of all living cells (animal and plant) in which oxygen is used to provide a source of energy for the cell. [NIH] Cell 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] Cellulitis: An acute, diffuse, and suppurative inflammation of loose connective tissue, particularly the deep subcutaneous tissues, and sometimes muscle, which is most commonly seen as a result of infection of a wound, ulcer, or other skin lesions. [NIH] Cellulose: A polysaccharide with glucose units linked as in cellobiose. It is the chief constituent of plant fibers, cotton being the purest natural form of the substance. As a raw material, it forms the basis for many derivatives used in chromatography, ion exchange materials, explosives manufacturing, and pharmaceutical preparations. [NIH] Centchroman: A non-steroidal anti-fertility agent with anti-hormonal properties. [NIH] Central Nervous System: The main information-processing organs of the nervous system, consisting of the brain, spinal cord, and meninges. [NIH] Cephaloridine: A cephalosporin antibiotic. [NIH] Cephalosporins: A group of broad-spectrum antibiotics first isolated from the Mediterranean fungus Acremonium (Cephalosporium acremonium). They contain the betalactam moiety thia-azabicyclo-octenecarboxylic acid also called 7-aminocephalosporanic acid. [NIH] Cerebral: Of or pertaining of the cerebrum or the brain. [EU]
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Cerebral Arteries: The arteries supplying the cerebral cortex. [NIH] Cerebral Cortex: The thin layer of gray matter on the surface of the cerebral hemisphere that develops from the telencephalon and folds into gyri. It reaches its highest development in man and is responsible for intellectual faculties and higher mental functions. [NIH] Cerebrovascular: Pertaining to the blood vessels of the cerebrum, or brain. [EU] Cerebrum: The largest part of the brain. It is divided into two hemispheres, or halves, called the cerebral hemispheres. The cerebrum controls muscle functions of the body and also controls speech, emotions, reading, writing, and learning. [NIH] Cervical: Relating to the neck, or to the neck of any organ or structure. Cervical lymph nodes are located in the neck; cervical cancer refers to cancer of the uterine cervix, which is the lower, narrow end (the "neck") of the uterus. [NIH] Cervix: The lower, narrow end of the uterus that forms a canal between the uterus and vagina. [NIH] Character: In current usage, approximately equivalent to personality. The sum of the relatively fixed personality traits and habitual modes of response of an individual. [NIH] Chelating Agents: Organic chemicals that form two or more coordination bonds with a central metal ion. Heterocyclic rings are formed with the central metal atom as part of the ring. Some biological systems form metal chelates, e.g., the iron-binding porphyrin group of hemoglobin and the magnesium-binding chlorophyll of plants. (From Hawley's Condensed Chemical Dictionary, 12th ed) They are used chemically to remove ions from solutions, medicinally against microorganisms, to treat metal poisoning, and in chemotherapy protocols. [NIH] Chemokines: Class of pro-inflammatory cytokines that have the ability to attract and activate leukocytes. They can be divided into at least three structural branches: C (chemokines, C), CC (chemokines, CC), and CXC (chemokines, CXC), according to variations in a shared cysteine motif. [NIH] Chemopreventive: Natural or synthetic compound used to intervene in the early precancerous stages of carcinogenesis. [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] Cherubism: A fibro-osseous hereditary disease of the jaws. The swollen jaws and raised eyes give a cherubic appearance; multiple radiolucencies are evident upon radiographic examination. [NIH] Chest cavity: Space in body surrounding the lungs. [NIH] Chest wall: The ribs and muscles, bones, and joints that make up the area of the body between the neck and the abdomen. [NIH] Chimeric Proteins: Proteins in individuals that are derived from genetically different zygotes. [NIH] Chin: The anatomical frontal portion of the mandible, also known as the mentum, that contains the line of fusion of the two separate halves of the mandible (symphysis menti).
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This line of fusion divides inferiorly to enclose a triangular area called the mental protuberance. On each side, inferior to the second premolar tooth, is the mental foramen for the passage of blood vessels and a nerve. [NIH] Chlamydia: A genus of the family Chlamydiaceae whose species cause a variety of diseases in vertebrates including humans, mice, and swine. Chlamydia species are gram-negative and produce glycogen. The type species is Chlamydia trachomatis. [NIH] Chlorhexidine: Disinfectant and topical anti-infective agent used also as mouthwash to prevent oral plaque. [NIH] Chlorophyll: Porphyrin derivatives containing magnesium that act to convert light energy in photosynthetic organisms. [NIH] 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] Chlortetracycline: An antibiotic substance isolated from the substrate of Streptomyces aureofaciens and used as an antibacterial and antiprotozoal agent. [NIH] Cholera: An acute diarrheal disease endemic in India and Southeast Asia whose causative agent is vibrio cholerae. This condition can lead to severe dehydration in a matter of hours unless quickly treated. [NIH] Cholera Toxin: The enterotoxin from Vibrio cholerae. It is a protein that consists of two major components, the heavy (H) or A peptide and the light (L) or B peptide or choleragenoid. The B peptide anchors the protein to intestinal epithelial cells, while the A peptide, enters the cytoplasm, and activates adenylate cyclase, and production of cAMP. Increased levels of cAMP are thought to modulate release of fluid and electrolytes from intestinal crypt cells. [NIH] Cholesterol: The principal sterol of all higher animals, distributed in body tissues, especially the brain and spinal cord, and in animal fats and oils. [NIH] Cholesterol Esters: Fatty acid esters of cholesterol which constitute about two-thirds of the cholesterol in the plasma. The accumulation of cholesterol esters in the arterial intima is a characteristic feature of atherosclerosis. [NIH] Cholinergic: Resembling acetylcholine in pharmacological action; stimulated by or releasing acetylcholine or a related compound. [EU] Chondrocytes: Polymorphic cells that form cartilage. [NIH] Chondroitin sulfate: The major glycosaminoglycan (a type of sugar molecule) in cartilage. [NIH]
Chorion: The outermost extraembryonic membrane. [NIH] Chorioretinitis: Inflammation of the choroid in which the sensory retina becomes edematous and opaque. The inflammatory cells and exudate may burst through the sensory retina to cloud the vitreous body. [NIH] Choroid: The thin, highly vascular membrane covering most of the posterior of the eye between the retina and sclera. [NIH] Choroidal Neovascularization: A pathological process consisting of the formation of new blood vessels in the choroid. [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
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human cells contain 46 chromosomes. [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 Obstructive Pulmonary Disease: Collective term for chronic bronchitis and emphysema. [NIH] Chronic renal: Slow and progressive loss of kidney function over several years, often resulting in end-stage renal disease. People with end-stage renal disease need dialysis or transplantation to replace the work of the kidneys. [NIH] Chylomicrons: A class of lipoproteins that carry dietary cholesterol and triglycerides from the small intestines to the tissues. [NIH] Cicatricial: Ectropion due to scar tissue on the margins or the surrounding surfaces of the eyelids. [NIH] Cilastatin: A renal dehydropeptidase-I and leukotriene D4 dipeptidase inhibitor. Since the antibiotic, imipenem, is hydrolyzed by dehydropeptidase-I, which resides in the brush border of the renal tubule, cilastatin is administered with imipenem to increase its effectiveness. The drug also inhibits the metabolism of leukotriene D4 to leukeotriene E4. [NIH]
Ciliary: Inflammation or infection of the glands of the margins of the eyelids. [NIH] Ciliary Neurotrophic Factor: A neurotrophic factor that promotes the survival of various neuronal cell types and may play an important role in the injury response in the nervous system. [NIH] Cinchona: A genus of rubiaceous South American trees that yields the toxic cinchona alkaloids from their bark; quinine, quinidine, chinconine, cinchonidine and others are used to treat malaria and cardiac arrhythmias. [NIH] Ciprofloxacin: A carboxyfluoroquinoline antimicrobial agent that is effective against a wide range of microorganisms. It has been successfully and safely used in the treatment of resistant respiratory, skin, bone, joint, gastrointestinal, urinary, and genital infections. [NIH] CIS: Cancer Information Service. The CIS is the National Cancer Institute's link to the public, interpreting and explaining research findings in a clear and understandable manner, and providing personalized responses to specific questions about cancer. Access the CIS by calling 1-800-4-CANCER, or by using the Web site at http://cis.nci.nih.gov. [NIH] Citric Acid: A key intermediate in metabolism. It is an acid compound found in citrus fruits. The salts of citric acid (citrates) can be used as anticoagulants due to their calcium chelating ability. [NIH] Citrus: Any tree or shrub of the Rue family or the fruit of these plants. [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] Clavulanic Acid: Clavulanic acid (C8H9O5N) and its salts and esters. The acid is a suicide inhibitor of bacterial beta-lactamase enzymes from Streptomyces clavuligerus. Administered alone, it has only weak antibacterial activity against most organisms, but given in combination with beta-lactam antibiotics prevents antibiotic inactivation by microbial lactamase. [NIH] Clear cell carcinoma: A rare type of tumor of the female genital tract in which the inside of the cells looks clear when viewed under a microscope. [NIH]
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Cleave: A double-stranded cut in DNA with a restriction endonuclease. [NIH] Cleft Lip: Congenital defect in the upper lip where the maxillary prominence fails to merge with the merged medial nasal prominences. It is thought to be caused by faulty migration of the mesoderm in the head region. [NIH] Clindamycin: An antibacterial agent that is a semisynthetic analog of lincomycin. [NIH] Clinical Medicine: The study and practice of medicine by direct examination of the patient. [NIH]
Clinical study: A research study in which patients receive treatment in a clinic or other medical facility. Reports of clinical studies can contain results for single patients (case reports) or many patients (case series or clinical trials). [NIH] Clinical trial: A research study that tests how well new medical treatments or other interventions work in people. Each study is designed to test new methods of screening, prevention, diagnosis, or treatment of a disease. [NIH] Clone: The term "clone" has acquired a new meaning. It is applied specifically to the bits of inserted foreign DNA in the hybrid molecules of the population. Each inserted segment originally resided in the DNA of a complex genome amid millions of other DNA segment. [NIH]
Cloning: The production of a number of genetically identical individuals; in genetic engineering, a process for the efficient replication of a great number of identical DNA molecules. [NIH] Coagulation: 1. The process of clot formation. 2. In colloid chemistry, the solidification of a sol into a gelatinous mass; an alteration of a disperse phase or of a dissolved solid which causes the separation of the system into a liquid phase and an insoluble mass called the clot or curd. Coagulation is usually irreversible. 3. In surgery, the disruption of tissue by physical means to form an amorphous residuum, as in electrocoagulation and photocoagulation. [EU] Coal: A natural fuel formed by partial decomposition of vegetable matter under certain environmental conditions. [NIH] Coccidioidomycosis: An infectious disease caused by a fungus, Coccidioides immitis, that is prevalent in the western United States and is acquired by inhalation of dust containing the spores. [NIH] Codons: Any triplet of nucleotides (coding unit) in DNA or RNA (if RNA is the carrier of primary genetic information as in some viruses) that codes for particular amino acid or signals the beginning or end of the message. [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]
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Collagenases: Enzymes that catalyze the degradation of collagen by acting on the peptide bonds. EC 3.4.24.-. [NIH] Collapse: 1. A state of extreme prostration and depression, with failure of circulation. 2. Abnormal falling in of the walls of any part of organ. [EU] Colloidal: Of the nature of a colloid. [EU] 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] Combination Therapy: Association of 3 drugs to treat AIDS (AZT + DDC or DDI + protease inhibitor). [NIH] Combinatorial: A cut-and-paste process that churns out thousands of potentially valuable compounds at once. [NIH] Commensal: 1. Living on or within another organism, and deriving benefit without injuring or benefiting the other individual. 2. An organism living on or within another, but not causing injury to the host. [EU] Comminuted Fractures: A fracture producing multiple fragments. [NIH] Compacta: Part of substantia nigra. [NIH] Complement: A term originally used to refer to the heat-labile factor in serum that causes immune cytolysis, the lysis of antibody-coated cells, and now referring to the entire functionally related system comprising at least 20 distinct serum proteins that is the effector not only of immune cytolysis but also of other biologic functions. Complement activation occurs by two different sequences, the classic and alternative pathways. The proteins of the classic pathway are termed 'components of complement' and are designated by the symbols C1 through C9. C1 is a calcium-dependent complex of three distinct proteins C1q, C1r and C1s. The proteins of the alternative pathway (collectively referred to as the properdin system) and complement regulatory proteins are known by semisystematic or trivial names. Fragments resulting from proteolytic cleavage of complement proteins are designated with lower-case letter suffixes, e.g., C3a. Inactivated fragments may be designated with the suffix 'i', e.g. C3bi. Activated components or complexes with biological activity are designated by a bar over the symbol e.g. C1 or C4b,2a. The classic pathway is activated by the binding of C1 to classic pathway activators, primarily antigen-antibody complexes containing IgM, IgG1, IgG3; C1q binds to a single IgM molecule or two adjacent IgG molecules. The alternative pathway can be activated by IgA immune complexes and also by nonimmunologic materials including bacterial endotoxins, microbial polysaccharides, and cell walls. Activation of the classic pathway triggers an enzymatic cascade involving C1, C4, C2 and C3; activation of the alternative pathway triggers a cascade involving C3 and factors B, D and P. Both result in the cleavage of C5 and the formation of the membrane attack complex. Complement activation also results in the formation of many biologically active complement fragments that act as anaphylatoxins, opsonins, or chemotactic factors. [EU] Complement Activation: The sequential activation of serum components C1 through C9, initiated by an erythrocyte-antibody complex or by microbial polysaccharides and properdin, and producing an inflammatory response. [NIH] Complementarity Determining Regions: Three regions (CDR1, CDR2 and CDR3) of amino acid sequence in theimmunoglobulin variable region that are highly divergent. Together the CDRs from the light and heavy immunoglobulin chains form a surface that is complementary to the antigen. These regions are also present in other members of the immunoglobulin superfamily, for example, T-cell receptors (receptors, antigen, T-cell). [NIH] Complementary and alternative medicine: CAM. Forms of treatment that are used in
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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] Complementation: The production of a wild-type phenotype when two different mutations are combined in a diploid or a heterokaryon and tested in trans-configuration. [NIH] Complete remission: The disappearance of all signs of cancer. Also called a complete response. [NIH] Compliance: Distensibility measure of a chamber such as the lungs (lung compliance) or bladder. Compliance is expressed as a change in volume per unit change in pressure. [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] Computer Simulation: Computer-based representation of physical systems and phenomena such as chemical processes. [NIH] Conception: The onset of pregnancy, marked by implantation of the blastocyst; the formation of a viable zygote. [EU] Cone: One of the special retinal receptor elements which are presumed to be primarily concerned with perception of light and color stimuli when the eye is adapted to light. [NIH] Congenita: Displacement, subluxation, or malposition of the crystalline lens. [NIH] Congestive heart failure: Weakness of the heart muscle that leads to a buildup of fluid in body tissues. [NIH] Conjugated: Acting or operating as if joined; simultaneous. [EU] Conjunctiva: The mucous membrane that lines the inner surface of the eyelids and the anterior part of the sclera. [NIH] Conjunctivitis: Inflammation of the conjunctiva, generally consisting of conjunctival hyperaemia associated with a discharge. [EU] Connective Tissue: Tissue that supports and binds other tissues. It consists of connective tissue cells embedded in a large amount of extracellular matrix. [NIH] Connective Tissue: Tissue that supports and binds other tissues. It consists of connective tissue cells embedded in a large amount of extracellular matrix. [NIH] Connective Tissue Cells: A group of cells that includes fibroblasts, cartilage cells, adipocytes, smooth muscle cells, and bone cells. [NIH] Consciousness: Sense of awareness of self and of the environment. [NIH] Constitutional: 1. Affecting the whole constitution of the body; not local. 2. Pertaining to the constitution. [EU] Constriction: The act of constricting. [NIH] Consumption: Pulmonary tuberculosis. [NIH]
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Contact dermatitis: Inflammation of the skin with varying degrees of erythema, edema and vesinculation resulting from cutaneous contact with a foreign substance or other exposure. [NIH]
Contamination: The soiling or pollution by inferior material, as by the introduction of organisms into a wound, or sewage into a stream. [EU] Contraception: Use of agents, devices, methods, or procedures which diminish the likelihood of or prevent conception. [NIH] Contraceptive: An agent that diminishes the likelihood of or prevents conception. [EU] Contraindications: Any factor or sign that it is unwise to pursue a certain kind of action or treatment, e. g. giving a general anesthetic to a person with pneumonia. [NIH] Contralateral: Having to do with the opposite side of the body. [NIH] Contrast medium: A substance that is introduced into or around a structure and, because of the difference in absorption of x-rays by the contrast medium and the surrounding tissues, allows radiographic visualization of the structure. [EU] Controlled clinical trial: A clinical study that includes a comparison (control) group. The comparison group receives a placebo, another treatment, or no treatment at all. [NIH] Controlled study: An experiment or clinical trial that includes a comparison (control) group. [NIH]
Conus: A large, circular, white patch around the optic disk due to the exposing of the sclera as a result of degenerative change or congenital abnormality in the choroid and retina. [NIH] Conventional therapy: A currently accepted and widely used treatment for a certain type of disease, based on the results of past research. Also called conventional treatment. [NIH] Conventional treatment: A currently accepted and widely used treatment for a certain type of disease, based on the results of past research. Also called conventional therapy. [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] Cor: The muscular organ that maintains the circulation of the blood. c. adiposum a heart that has undergone fatty degeneration or that has an accumulation of fat around it; called also fat or fatty, heart. c. arteriosum the left side of the heart, so called because it contains oxygenated (arterial) blood. c. biloculare a congenital anomaly characterized by failure of formation of the atrial and ventricular septums, the heart having only two chambers, a single atrium and a single ventricle, and a common atrioventricular valve. c. bovinum (L. 'ox heart') a greatly enlarged heart due to a hypertrophied left ventricle; called also c. taurinum and bucardia. c. dextrum (L. 'right heart') the right atrium and ventricle. c. hirsutum, c. villosum. c. mobile (obs.) an abnormally movable heart. c. pendulum a heart so movable that it seems to be hanging by the great blood vessels. c. pseudotriloculare biatriatum a congenital cardiac anomaly in which the heart functions as a three-chambered heart because of tricuspid atresia, the right ventricle being extremely small or rudimentary and the right atrium greatly dilated. Blood passes from the right to the left atrium and thence disease due to pulmonary hypertension secondary to disease of the lung, or its blood vessels, with hypertrophy of the right ventricle. [EU] Cornea: The transparent part of the eye that covers the iris and the pupil and allows light to enter the inside. [NIH] Corneal Stroma: The lamellated connective tissue constituting the thickest layer of the cornea between the Bowman and Descemet membranes. [NIH] Corneal Ulcer: Loss of epithelial tissue from the surface of the cornea due to progressive erosion and necrosis of the tissue; usually caused by bacterial, fungal, or viral infection. [NIH]
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Corneum: The superficial layer of the epidermis containing keratinized cells. [NIH] Coronary: Encircling in the manner of a crown; a term applied to vessels; nerves, ligaments, etc. The term usually denotes the arteries that supply the heart muscle and, by extension, a pathologic involvement of them. [EU] Coronary Arteriosclerosis: Thickening and loss of elasticity of the coronary arteries. [NIH] Coronary Thrombosis: Presence of a thrombus in a coronary artery, often causing a myocardial infarction. [NIH] Corpus: The body of the uterus. [NIH] Corpus Luteum: The yellow glandular mass formed in the ovary by an ovarian follicle that has ruptured and discharged its ovum. [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] Courtship: The mutual attraction between individuals of the opposite sex. [NIH] Cowpox: A mild, eruptive skin disease of milk cows caused by cowpox virus, with lesions occurring principally on the udder and teats. Human infection may occur while milking an infected animal. [NIH] Cowpox Virus: A species of orthopoxvirus that is the etiologic agent of cowpox. It is closely related to but antigenically different from vaccina virus. [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] Crossing-over: The exchange of corresponding segments between chromatids of homologous chromosomes during meiosia, forming a chiasma. [NIH] Croton Oil: Viscous, nauseating oil obtained from the shrub Croton tiglium (Euphorbaceae). It is a vesicant and skin irritant used as pharmacologic standard for skin inflammation and allergy and causes skin cancer. It was formerly used as an emetic and cathartic with frequent
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mortality. [NIH] Cryptococcosis: Infection with a fungus of the species Cryptococcus neoformans. [NIH] Cryptosporidiosis: Parasitic intestinal infection with severe diarrhea caused by a protozoan, Cryptosporidium. It occurs in both animals and humans. [NIH] Culture Media: Any liquid or solid preparation made specifically for the growth, storage, or transport of microorganisms or other types of cells. The variety of media that exist allow for the culturing of specific microorganisms and cell types, such as differential media, selective media, test media, and defined media. Solid media consist of liquid media that have been solidified with an agent such as agar or gelatin. [NIH] Curative: Tending to overcome disease and promote recovery. [EU] Curettage: Removal of tissue with a curette, a spoon-shaped instrument with a sharp edge. [NIH]
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] Cyst: A sac or capsule filled with fluid. [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]
Cystitis: Inflammation of the urinary bladder. [EU] Cytochrome: Any electron transfer hemoprotein having a mode of action in which the transfer of a single electron is effected by a reversible valence change of the central iron atom of the heme prosthetic group between the +2 and +3 oxidation states; classified as cytochromes a in which the heme contains a formyl side chain, cytochromes b, which contain protoheme or a closely similar heme that is not covalently bound to the protein, cytochromes c in which protoheme or other heme is covalently bound to the protein, and cytochromes d in which the iron-tetrapyrrole has fewer conjugated double bonds than the hemes have. Well-known cytochromes have been numbered consecutively within groups and are designated by subscripts (beginning with no subscript), e.g. cytochromes c, c1, C2, . New cytochromes are named according to the wavelength in nanometres of the absorption maximum of the a-band of the iron (II) form in pyridine, e.g., c-555. [EU] Cytokine: Small but highly potent protein that modulates the activity of many cell types, including T and B cells. [NIH] Cytomegalovirus: A genus of the family Herpesviridae, subfamily Betaherpesvirinae, infecting the salivary glands, liver, spleen, lungs, eyes, and other organs, in which they produce characteristically enlarged cells with intranuclear inclusions. Infection with Cytomegalovirus is also seen as an opportunistic infection in AIDS. [NIH]
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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] Cytoskeletal Proteins: Major constituent of the cytoskeleton found in the cytoplasm of eukaryotic cells. They form a flexible framework for the cell, provide attachment points for organelles and formed bodies, and make communication between parts of the cell possible. [NIH]
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] Databases, Bibliographic: Extensive collections, reputedly complete, of references and citations to books, articles, publications, etc., generally on a single subject or specialized subject area. Databases can operate through automated files, libraries, or computer disks. The concept should be differentiated from factual databases which is used for collections of data and facts apart from bibliographic references to them. [NIH] Daunorubicin: Very toxic anthracycline aminoglycoside antibiotic isolated from Streptomyces peucetius and others, used in treatment of leukemias and other neoplasms. [NIH]
De novo: In cancer, the first occurrence of cancer in the body. [NIH] Deamination: The removal of an amino group (NH2) from a chemical compound. [NIH] Decarboxylation: The removal of a carboxyl group, usually in the form of carbon dioxide, from a chemical compound. [NIH] Decidua: The epithelial lining of the endometrium that is formed before the fertilized ovum reaches the uterus. The fertilized ovum embeds in the decidua. If the ovum is not fertilized, the decidua is shed during menstruation. [NIH] Defense Mechanisms: Unconscious process used by an individual or a group of individuals in order to cope with impulses, feelings or ideas which are not acceptable at their conscious level; various types include reaction formation, projection and self reversal. [NIH] Degenerative: Undergoing degeneration : tending to degenerate; having the character of or involving degeneration; causing or tending to cause degeneration. [EU] Dehydration: The condition that results from excessive loss of body water. [NIH] Dehydroepiandrosterone: DHEA. A substance that is being studied as a cancer prevention drug. It belongs to the family of drugs called steroids. [NIH] Deletion: A genetic rearrangement through loss of segments of DNA (chromosomes), bringing sequences, which are normally separated, into close proximity. [NIH] Demeclocycline: An antibiotic related to tetracycline and produced by Streptomyces aureofaciens. Because it is excreted more slowly than tetracycline, it maintains effective blood levels for longer periods of time. [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] Denaturation: Rupture of the hydrogen bonds by heating a DNA solution and then cooling
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it rapidly causes the two complementary strands to separate. [NIH] Dendrites: Extensions of the nerve cell body. They are short and branched and receive stimuli from other neurons. [NIH] Dendritic: 1. Branched like a tree. 2. Pertaining to or possessing dendrites. [EU] Dendritic cell: A special type of antigen-presenting cell (APC) that activates T lymphocytes. [NIH]
Dens in Dente: Anomaly of the tooth, found chiefly in upper lateral incisors. It is characterized by invagination of the enamel at the incisal edge. [NIH] Density: The logarithm to the base 10 of the opacity of an exposed and processed film. [NIH] Dental Care: The total of dental diagnostic, preventive, and restorative services provided to meet the needs of a patient (from Illustrated Dictionary of Dentistry, 1982). [NIH] Dental Caries: Localized destruction of the tooth surface initiated by decalcification of the enamel followed by enzymatic lysis of organic structures and leading to cavity formation. If left unchecked, the cavity may penetrate the enamel and dentin and reach the pulp. The three most prominent theories used to explain the etiology of the disase are that acids produced by bacteria lead to decalcification; that micro-organisms destroy the enamel protein; or that keratolytic micro-organisms produce chelates that lead to decalcification. [NIH]
Dental Plaque: A film that attaches to teeth, often causing dental caries and gingivitis. It is composed of mucins, secreted from salivary glands, and microorganisms. [NIH] Dentin Dysplasia: Abnormal tissue development or growth occurring subsequent to the appearance of the primordial cells. [NIH] Dentists: Individuals licensed to practice dentistry. [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] Dermal: Pertaining to or coming from the skin. [NIH] Dermatitis: Any inflammation of the skin. [NIH] Dermatitis, Contact: A type of acute or chronic skin reaction in which sensitivity is manifested by reactivity to materials or substances coming in contact with the skin. It may involve allergic or non-allergic mechanisms. [NIH] Dermatosis: Any skin disease, especially one not characterized by inflammation. [EU] DES: Diethylstilbestrol. A synthetic hormone that was prescribed from the early 1940s until 1971 to help women with complications of pregnancy. DES has been linked to an increased risk of clear cell carcinoma of the vagina in daughters of women who used DES. DES may also increase the risk of breast cancer in women who used DES. [NIH] Desmin: An intermediate filament protein found predominantly in smooth, skeletal, and cardiac muscle cells. Localized at the Z line. MW 50,000 to 55,000 is species dependent. [NIH] Desmosomes: Attachment bodies between cells such as in the corneal epithelium, which possibly allow tonofibrils to pass from cell to cell and which can degenerate to allow cells to migrate to cover a denuded area. [NIH] Deuterium: Deuterium. The stable isotope of hydrogen. It has one neutron and one proton in the nucleus. [NIH] Developing Countries: Countries in the process of change directed toward economic growth, that is, an increase in production, per capita consumption, and income. The process of economic growth involves better utilization of natural and human resources, which
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results in a change in the social, political, and economic structures. [NIH] Developmental Biology: The field of biology which deals with the process of the growth and differentiation of an organism. [NIH] Dexamethasone: (11 beta,16 alpha)-9-Fluoro-11,17,21-trihydroxy-16-methylpregna-1,4diene-3,20-dione. An anti-inflammatory glucocorticoid used either in the free alcohol or esterified form in treatment of conditions that respond generally to cortisone. [NIH] Diabetes Mellitus: A heterogeneous group of disorders that share glucose intolerance in common. [NIH] Diabetic Retinopathy: Retinopathy associated with diabetes mellitus, which may be of the background type, progressively characterized by microaneurysms, interretinal punctuate macular edema, or of the proliferative type, characterized by neovascularization of the retina and optic disk, which may project into the vitreous, proliferation of fibrous tissue, vitreous hemorrhage, and retinal detachment. [NIH] Diagnostic procedure: A method used to identify a disease. [NIH] Diaphragm: The musculofibrous partition that separates the thoracic cavity from the abdominal cavity. Contraction of the diaphragm increases the volume of the thoracic cavity aiding inspiration. [NIH] Diarrhea: Passage of excessively liquid or excessively frequent stools. [NIH] Diastolic: Of or pertaining to the diastole. [EU] Diencephalon: The paired caudal parts of the prosencephalon from which the thalamus, hypothalamus, epithalamus, and subthalamus are derived. [NIH] Dietary Fats: Fats present in food, especially in animal products such as meat, meat products, butter, ghee. They are present in lower amounts in nuts, seeds, and avocados. [NIH]
Diffusion: The tendency of a gas or solute to pass from a point of higher pressure or concentration to a point of lower pressure or concentration and to distribute itself throughout the available space; a major mechanism of biological transport. [NIH] Digestion: The process of breakdown of food for metabolism and use by the body. [NIH] Digestive system: The organs that take in food and turn it into products that the body can use to stay healthy. Waste products the body cannot use leave the body through bowel movements. The digestive system includes the salivary glands, mouth, esophagus, stomach, liver, pancreas, gallbladder, small and large intestines, and rectum. [NIH] Digestive tract: The organs through which food passes when food is eaten. These organs are the mouth, esophagus, stomach, small and large intestines, and rectum. [NIH] Dilatation: The act of dilating. [NIH] Dilated cardiomyopathy: Heart muscle disease that leads to enlargement of the heart's chambers, robbing the heart of its pumping ability. [NIH] Dilution: A diluted or attenuated medicine; in homeopathy, the diffusion of a given quantity of a medicinal agent in ten or one hundred times the same quantity of water. [NIH] Dimerization: The process by which two molecules of the same chemical composition form a condensation product or polymer. [NIH] Dimethyl: A volatile metabolite of the amino acid methionine. [NIH] Dimethyl Sulfoxide: A highly polar organic liquid, that is used widely as a chemical solvent. Because of its ability to penetrate biological membranes, it is used as a vehicle for topical application of pharmaceuticals. It is also used to protect tissue during
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cryopreservation. Dimethyl sulfoxide shows a range of pharmacological activity including analgesia and anti-inflammation. [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] Discrete: Made up of separate parts or characterized by lesions which do not become blended; not running together; separate. [NIH] 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] 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] Dopa: The racemic or DL form of DOPA, an amino acid found in various legumes. The dextro form has little physiologic activity but the levo form (levodopa) is a very important physiologic mediator and precursor and pharmacological agent. [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] Dopamine Agonists: Drugs that bind to and activate dopamine receptors. [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] Dosage Forms: Completed forms of the pharmaceutical preparation in which prescribed doses of medication are included. They are designed to resist action by gastric fluids, prevent vomiting and nausea, reduce or alleviate the undesirable taste and smells associated with oral administration, achieve a high concentration of drug at target site, or produce a delayed or long-acting drug effect. They include capsules, liniments, ointments, pharmaceutical solutions, powders, tablets, etc. [NIH] Dose-limiting: Describes side effects of a drug or other treatment that are serious enough to prevent an increase in dose or level of that treatment. [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
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hydroxy derivative of daunorubicin and is used in treatment of both leukemia and solid tumors. [NIH] Doxycycline: A synthetic tetracycline derivative with a range of antimicrobial activity and mode of action similar to that of tetracycline, but more effective against many species. Animal studies suggest that it may cause less tooth staining than other tetracyclines. [NIH] Drive: A state of internal activity of an organism that is a necessary condition before a given stimulus will elicit a class of responses; e.g., a certain level of hunger (drive) must be present before food will elicit an eating response. [NIH] Drug Combinations: Single preparations containing two or more active agents, for the purpose of their concurrent administration as a fixed dose mixture. It is differentiated from combination drug therapy in which two or more drugs are administered separately for a combined effect. [NIH] Drug Design: The molecular designing of drugs for specific purposes (such as DNAbinding, enzyme inhibition, anti-cancer efficacy, etc.) based on knowledge of molecular properties such as activity of functional groups, molecular geometry, and electronic structure, and also on information cataloged on analogous molecules. Drug design is generally computer-assisted molecular modeling and does not include pharmacokinetics, dosage analysis, or drug administration analysis. [NIH] Drug Interactions: The action of a drug that may affect the activity, metabolism, or toxicity of another drug. [NIH] Drug Resistance: Diminished or failed response of an organism, disease or tissue to the intended effectiveness of a chemical or drug. It should be differentiated from drug tolerance which is the progressive diminution of the susceptibility of a human or animal to the effects of a drug, as a result of continued administration. [NIH] Drug Tolerance: Progressive diminution of the susceptibility of a human or animal to the effects of a drug, resulting from its continued administration. It should be differentiated from drug resistance wherein an organism, disease, or tissue fails to respond to the intended effectiveness of a chemical or drug. It should also be differentiated from maximum tolerated dose and no-observed-adverse-effect level. [NIH] Drusen: Tiny yellow or white deposits in the retina or optic nerve head. [NIH] Duct: A tube through which body fluids pass. [NIH] Duodenal Ulcer: An ulcer in the lining of the first part of the small intestine (duodenum). [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] Dysmenorrhea: Painful menstruation. [NIH] Dysplasia: Cells that look abnormal under a microscope but are not cancer. [NIH] Dystrophic: Pertaining to toxic habitats low in nutrients. [NIH] Dystrophin: A muscle protein localized in surface membranes which is the product of the Duchenne/Becker muscular dystrophy gene. Individuals with Duchenne muscular dystrophy usually lack dystrophin completely while those with Becker muscular dystrophy have dystrophin of an altered size. It shares features with other cytoskeletal proteins such as
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spectrin and alpha-actinin but the precise function of dystrophin is not clear. One possible role might be to preserve the integrity and alignment of the plasma membrane to the myofibrils during muscle contraction and relaxation. MW 400 kDa. [NIH] Dystrophy: Any disorder arising from defective or faulty nutrition, especially the muscular dystrophies. [EU] Echocardiography: Ultrasonic recording of the size, motion, and composition of the heart and surrounding tissues. The standard approach is transthoracic. [NIH] Ectoderm: The outer of the three germ layers of the embryo. [NIH] Ectodermal Dysplasia: A group of hereditary disorders involving tissues and structures derived from the embryonic ectoderm. They are characterized by the presence of abnormalities at birth and involvement of both the epidermis and skin appendages. They are generally nonprogressive and diffuse. Various forms exist, including anhidrotic and hidrotic dysplasias, focal dermal hypoplasia, and aplasia cutis congenita. [NIH] Ectopic: Pertaining to or characterized by ectopia. [EU] Edeine: Basic peptide antibiotic from Bacillus brevis. It exhibits broad-spectrum antibacterial activity and inhibits bacterial DNA synthesis. [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] Eicosanoids: A class of oxygenated, endogenous, unsaturated fatty acids derived from arachidonic acid. They include prostaglandins, leukotrienes, thromboxanes, and hydroxyeicosatetraenoic acid compounds (HETE). They are hormone-like substances that act near the site of synthesis without altering functions throughout the body. [NIH] Elastic: Susceptible of resisting and recovering from stretching, compression or distortion applied by a force. [EU] 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] 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]
Electroplating: Coating with a metal or alloy by electrolysis. [NIH] Electroporation: A technique in which electric pulses of intensity in kilovolts per centimeter and of microsecond-to-millisecond duration cause a temporary loss of the semipermeability of cell membranes, thus leading to ion leakage, escape of metabolites, and increased uptake by cells of drugs, molecular probes, and DNA. Some applications of electroporation include
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introduction of plasmids or foreign DNA into living cells for transfection, fusion of cells to prepare hybridomas, and insertion of proteins into cell membranes. [NIH] Electroretinography: Recording of electric potentials in the retina after stimulation by light. [NIH]
Emboli: Bit of foreign matter which enters the blood stream at one point and is carried until it is lodged or impacted in an artery and obstructs it. It may be a blood clot, an air bubble, fat or other tissue, or clumps of bacteria. [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] Embolization: The blocking of an artery by a clot or foreign material. Embolization can be done as treatment to block the flow of blood to a tumor. [NIH] Embolus: Bit of foreign matter which enters the blood stream at one point and is carried until it is lodged or impacted in an artery and obstructs it. It may be a blood clot, an air bubble, fat or other tissue, or clumps of bacteria. [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] Embryology: The study of the development of an organism during the embryonic and fetal stages of life. [NIH] Emollient: Softening or soothing; called also malactic. [EU] Emphysema: A pathological accumulation of air in tissues or organs. [NIH] Empirical: A treatment based on an assumed diagnosis, prior to receiving confirmatory laboratory test results. [NIH] Empyema: Presence of pus in a hollow organ or body cavity. [NIH] Emulsion: A preparation of one liquid distributed in small globules throughout the body of a second liquid. The dispersed liquid is the discontinuous phase, and the dispersion medium is the continuous phase. When oil is the dispersed liquid and an aqueous solution is the continuous phase, it is known as an oil-in-water emulsion, whereas when water or aqueous solution is the dispersed phase and oil or oleaginous substance is the continuous phase, it is known as a water-in-oil emulsion. Pharmaceutical emulsions for which official standards have been promulgated include cod liver oil emulsion, cod liver oil emulsion with malt, liquid petrolatum emulsion, and phenolphthalein in liquid petrolatum emulsion. [EU] Enamel: A very hard whitish substance which covers the dentine of the anatomical crown of a tooth. [NIH] Enamel Microabrasion: Mechanical removal of a small amount of tooth structure (not more than a few tenths of a millimeter in depth) to eliminate superficial enamel discoloration defects not successfully removed by bleaching techniques. A common abrasive is a mixture of pumice and hydrochloric acid. [NIH] Encapsulated: Confined to a specific, localized area and surrounded by a thin layer of tissue. [NIH]
Encephalitis: Inflammation of the brain due to infection, autoimmune processes, toxins, and other conditions. Viral infections (see encephalitis, viral) are a relatively frequent cause of this condition. [NIH]
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Encephalitis, Viral: Inflammation of brain parenchymal tissue as a result of viral infection. Encephalitis may occur as primary or secondary manifestation of Togaviridae infections; Herpesviridae infections; Adenoviridae infections; Flaviviridae infections; Bunyaviridae infections; Picornaviridae infections; Paramyxoviridae infections; Orthomyxoviridae infections; Retroviridae infections; and Arenaviridae infections. [NIH] 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] Endocarditis: Exudative and proliferative inflammatory alterations of the endocardium, characterized by the presence of vegetations on the surface of the endocardium or in the endocardium itself, and most commonly involving a heart valve, but sometimes affecting the inner lining of the cardiac chambers or the endocardium elsewhere. It may occur as a primary disorder or as a complication of or in association with another disease. [EU] Endocardium: The innermost layer of the heart, comprised of endothelial cells. [NIH] Endocytosis: Cellular uptake of extracellular materials within membrane-limited vacuoles or microvesicles. Endosomes play a central role in endocytosis. [NIH] Endodontics: A dental specialty concerned with the maintenance of the dental pulp in a state of health and the treatment of the pulp cavity (pulp chamber and pulp canal). [NIH] Endogenous: Produced inside an organism or cell. The opposite is external (exogenous) production. [NIH] Endometrium: The layer of tissue that lines the uterus. [NIH] Endoscopy: Endoscopic examination, therapy or surgery performed on interior parts of the body. [NIH] Endothelial cell: The main type of cell found in the inside lining of blood vessels, lymph vessels, and the heart. [NIH] Endothelium: A layer of epithelium that lines the heart, blood vessels (endothelium, vascular), lymph vessels (endothelium, lymphatic), and the serous cavities of the body. [NIH] Endothelium, Lymphatic: Unbroken cellular lining (intima) of the lymph vessels (e.g., the high endothelial lymphatic venules). It is more permeable than vascular endothelium, lacking selective absorption and functioning mainly to remove plasma proteins that have filtered through the capillaries into the tissue spaces. [NIH] Endothelium, Vascular: Single pavement layer of cells which line the luminal surface of the entire vascular system and regulate the transport of macromolecules and blood components from interstitium to lumen; this function has been most intensively studied in the blood capillaries. [NIH] Endothelium-derived: Small molecule that diffuses to the adjacent muscle layer and relaxes it. [NIH] Endotoxemia: A condition characterized by the presence of endotoxins in the blood. If endotoxemia is the result of gram-negative rod-shaped bacteria, shock may occur. [NIH] Endotoxic: Of, relating to, or acting as an endotoxin (= a heat-stable toxin, associated with the outer membranes of certain gram-negative bacteria. Endotoxins are not secreted and are released only when the cells are disrupted). [EU] Endotoxin: Toxin from cell walls of bacteria. [NIH] End-stage renal: Total chronic kidney failure. When the kidneys fail, the body retains fluid
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and harmful wastes build up. A person with ESRD needs treatment to replace the work of the failed kidneys. [NIH] Enhancer: Transcriptional element in the virus genome. [NIH] Enteritis: Inflammation of the intestine, applied chiefly to inflammation of the small intestine; see also enterocolitis. [EU] Enterocolitis: Inflammation of the intestinal mucosa of the small and large bowel. [NIH] Enteropeptidase: A specialized proteolytic enzyme secreted by intestinal cells. It converts trypsinogen into its active form trypsin by removing the N-terminal peptide. EC 3.4.21.9. [NIH]
Environmental Exposure: The exposure to potentially harmful chemical, physical, or biological agents in the environment or to environmental factors that may include ionizing radiation, pathogenic organisms, or toxic chemicals. [NIH] Environmental Health: The science of controlling or modifying those conditions, influences, or forces surrounding man which relate to promoting, establishing, and maintaining health. [NIH]
Enzymatic: Phase where enzyme cuts the precursor protein. [NIH] Enzyme: A protein that speeds up chemical reactions in the body. [NIH] Enzyme Induction: An increase in the rate of synthesis of an enzyme due to the presence of an inducer which acts to derepress the gene responsible for enzyme synthesis. [NIH] Enzyme Inhibitors: Compounds or agents that combine with an enzyme in such a manner as to prevent the normal substrate-enzyme combination and the catalytic reaction. [NIH] Enzyme Repression: The interference in synthesis of an enzyme due to the elevated level of an effector substance, usually a metabolite, whose presence would cause depression of the gene responsible for enzyme synthesis. [NIH] Eosinophils: Granular leukocytes with a nucleus that usually has two lobes connected by a slender thread of chromatin, and cytoplasm containing coarse, round granules that are uniform in size and stainable by eosin. [NIH] Epidemic: Occurring suddenly in numbers clearly in excess of normal expectancy; said especially of infectious diseases but applied also to any disease, injury, or other healthrelated event occurring in such outbreaks. [EU] Epidemiological: Relating to, or involving epidemiology. [EU] Epidermal: Pertaining to or resembling epidermis. Called also epidermic or epidermoid. [EU] Epidermal Growth Factor: A 6 kD polypeptide growth factor initially discovered in mouse submaxillary glands. Human epidermal growth factor was originally isolated from urine based on its ability to inhibit gastric secretion and called urogastrone. epidermal growth factor exerts a wide variety of biological effects including the promotion of proliferation and differentiation of mesenchymal and epithelial cells. [NIH] Epidermal growth factor receptor: EGFR. The protein found on the surface of some cells and to which epidermal growth factor binds, causing the cells to divide. It is found at abnormally high levels on the surface of many types of cancer cells, so these cells may divide excessively in the presence of epidermal growth factor. Also known as ErbB1 or HER1. [NIH] Epidermis: Nonvascular layer of the skin. It is made up, from within outward, of five layers: 1) basal layer (stratum basale epidermidis); 2) spinous layer (stratum spinosum epidermidis); 3) granular layer (stratum granulosum epidermidis); 4) clear layer (stratum lucidum epidermidis); and 5) horny layer (stratum corneum epidermidis). [NIH] Epinephrine: The active sympathomimetic hormone from the adrenal medulla in most
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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] Epistaxis: Bleeding from the nose. [NIH] Epithelial: Refers to the cells that line the internal and external surfaces of the body. [NIH] Epithelial Cells: Cells that line the inner and outer surfaces of the body. [NIH] Epithelium: One or more layers of epithelial cells, supported by the basal lamina, which covers the inner or outer surfaces of the body. [NIH] Epitope: A molecule or portion of a molecule capable of binding to the combining site of an antibody. For every given antigenic determinant, the body can construct a variety of antibody-combining sites, some of which fit almost perfectly, and others which barely fit. [NIH]
ERV: The expiratory reserve volume is the largest volume of gas that can be expired from the end-expiratory level. [NIH] Erythema: Redness of the skin produced by congestion of the capillaries. This condition may result from a variety of causes. [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] Esophageal: Having to do with the esophagus, the muscular tube through which food passes from the throat to the stomach. [NIH] Esophageal Varices: Stretched veins in the esophagus that occur when the liver is not working properly. If the veins burst, the bleeding can cause death. [NIH] Esophagitis: Inflammation, acute or chronic, of the esophagus caused by bacteria, chemicals, or trauma. [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] Estrogen receptor: ER. Protein found on some cancer cells to which estrogen will attach. [NIH]
Estrogen Receptor Modulators: Substances that possess antiestrogenic actions but can also produce estrogenic effects as well. They act as complete or partial agonist or as antagonist. They can be either steroidal or nonsteroidal in structure. [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] Etidronate: A drug that belongs to the family of drugs called bisphosphonates. Bisphosphonates are used as treatment for hypercalcemia (abnormally high levels of calcium in the blood) and for cancer that has spread to the bone (bone metastases). [NIH] Eukaryotic Cells: Cells of the higher organisms, containing a true nucleus bounded by a
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nuclear membrane. [NIH] Europium: An element of the rare earth family of metals. It has the atomic symbol Eu, atomic number 63, and atomic weight 152. Europium is used in the form of its salts as coatings for cathode ray tubes and in the form of its organic derivatives as shift reagents in NMR spectroscopy. [NIH] Evoke: The electric response recorded from the cerebral cortex after stimulation of a peripheral sense organ. [NIH] Excitability: Property of a cardiac cell whereby, when the cell is depolarized to a critical level (called threshold), the membrane becomes permeable and a regenerative inward current causes an action potential. [NIH] Excitation: An act of irritation or stimulation or of responding to a stimulus; the addition of energy, as the excitation of a molecule by absorption of photons. [EU] Excitatory: When cortical neurons are excited, their output increases and each new input they receive while they are still excited raises their output markedly. [NIH] Excitotoxicity: Excessive exposure to glutamate or related compounds can kill brain neurons, presumably by overstimulating them. [NIH] Excrete: To get rid of waste from the body. [NIH] Exfoliation: A falling off in scales or layers. [EU] Exhaustion: The feeling of weariness of mind and body. [NIH] 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] Exotoxin: Toxic substance excreted by living bacterial cells. [NIH] Expiration: The act of breathing out, or expelling air from the lungs. [EU] Expiratory: The volume of air which leaves the breathing organs in each expiration. [NIH] Expiratory Reserve Volume: The extra volume of air that can be expired with maximum effort beyond the level reached at the end of a normal, quiet expiration. Common abbreviation is ERV. [NIH] Extensor: A muscle whose contraction tends to straighten a limb; the antagonist of a flexor. [NIH]
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] Extracellular Matrix Proteins: Macromolecular organic compounds that contain carbon, hydrogen, oxygen, nitrogen, and usually, sulfur. These macromolecules (proteins) form an intricate meshwork in which cells are embedded to construct tissues. Variations in the relative types of macromolecules and their organization determine the type of extracellular matrix, each adapted to the functional requirements of the tissue. The two main classes of
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macromolecules that form the extracellular matrix are: glycosaminoglycans, usually linked to proteins (proteoglycans), and fibrous proteins (e.g., collagen, elastin, fibronectins and laminin). [NIH] Extracellular Space: Interstitial space between cells, occupied by fluid as well as amorphous and fibrous substances. [NIH] Extraction: The process or act of pulling or drawing out. [EU] Extrapyramidal: Outside of the pyramidal tracts. [EU] Eye Infections: Infection, moderate to severe, caused by bacteria, fungi, or viruses, which occurs either on the external surface of the eye or intraocularly with probable inflammation, visual impairment, or blindness. [NIH] Facial: Of or pertaining to the face. [EU] Family Planning: Programs or services designed to assist the family in controlling reproduction by either improving or diminishing fertility. [NIH] Fat: Total lipids including phospholipids. [NIH] Fatigue: The state of weariness following a period of exertion, mental or physical, characterized by a decreased capacity for work and reduced efficiency to respond to stimuli. [NIH]
Fatty acids: A major component of fats that are used by the body for energy and tissue development. [NIH] Fatty Liver: The buildup of fat in liver cells. The most common cause is alcoholism. Other causes include obesity, diabetes, and pregnancy. Also called steatosis. [NIH] Febrile: Pertaining to or characterized by fever. [EU] Femoral: Pertaining to the femur, or to the thigh. [EU] Femur: The longest and largest bone of the skeleton, it is situated between the hip and the knee. [NIH] Fertilizers: Substances or mixtures that are added to the soil to supply nutrients or to make available nutrients already present in the soil, in order to increase plant growth and productivity. [NIH] Fetus: The developing offspring from 7 to 8 weeks after conception until birth. [NIH] Fibrin: A protein derived from fibrinogen in the presence of thrombin, which forms part of the blood clot. [NIH] Fibrinogen: Plasma glycoprotein clotted by thrombin, composed of a dimer of three nonidentical pairs of polypeptide chains (alpha, beta, gamma) held together by disulfide bonds. Fibrinogen clotting is a sol-gel change involving complex molecular arrangements: whereas fibrinogen is cleaved by thrombin to form polypeptides A and B, the proteolytic action of other enzymes yields different fibrinogen degradation products. [NIH] Fibrinolytic: Pertaining to, characterized by, or causing the dissolution of fibrin by enzymatic action [EU] Fibroblast Growth Factor: Peptide isolated from the pituitary gland and from the brain. It is a potent mitogen which stimulates growth of a variety of mesodermal cells including chondrocytes, granulosa, and endothelial cells. The peptide may be active in wound healing and animal limb regeneration. [NIH] Fibroblasts: Connective tissue cells which secrete an extracellular matrix rich in collagen and other macromolecules. [NIH] Fibrosis: Any pathological condition where fibrous connective tissue invades any organ,
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usually as a consequence of inflammation or other injury. [NIH] Fistula: Abnormal communication most commonly seen between two internal organs, or between an internal organ and the surface of the body. [NIH] 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] Flow Injection Analysis: The analysis of a chemical substance by inserting a sample into a carrier stream of reagent using a sample injection valve that propels the sample downstream where mixing occurs in a coiled tube, then passes into a flow-through detector and a recorder or other data handling device. [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] Fluorine: A nonmetallic, diatomic gas that is a trace element and member of the halogen family. It is used in dentistry as flouride to prevent dental caries. [NIH] Fluorosis: Discoloration of the tooth enamel due to fluorine. [NIH] Flushing: A transient reddening of the face that may be due to fever, certain drugs, exertion, stress, or a disease process. [NIH] Folate: A B-complex vitamin that is being studied as a cancer prevention agent. Also called folic acid. [NIH] Fold: A plication or doubling of various parts of the body. [NIH] Folic Acid: N-(4-(((2-Amino-1,4-dihydro-4-oxo-6-pteridinyl)methyl)amino)benzoyl)-Lglutamic acid. A member of the vitamin B family that stimulates the hematopoietic system. It is present in the liver and kidney and is found in mushrooms, spinach, yeast, green leaves, and grasses. Folic acid is used in the treatment and prevention of folate deficiencies and megaloblastic anemia. [NIH] Follicles: Shafts through which hair grows. [NIH] Foodborne Illness: An acute gastrointestinal infection caused by food that contains harmful bacteria. Symptoms include diarrhea, abdominal pain, fever, and chills. Also called food poisoning. [NIH] Foramen: A natural hole of perforation, especially one in a bone. [NIH] Forearm: The part between the elbow and the wrist. [NIH] Fovea: The central part of the macula that provides the sharpest vision. [NIH]
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Frameshift: A type of mutation which causes out-of-phase transcription of the base sequence; such mutations arise from the addition or delection of nucleotide(s) in numbers other than 3 or multiples of 3. [NIH] Frameshift Mutation: A type of mutation in which a number of nucleotides not divisible by three is deleted from or inserted into a coding sequence, thereby causing an alteration in the reading frame of the entire sequence downstream of the mutation. These mutations may be induced by certain types of mutagens or may occur spontaneously. [NIH] 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] Fungi: A kingdom of eukaryotic, heterotrophic organisms that live as saprobes or parasites, including mushrooms, yeasts, smuts, molds, etc. They reproduce either sexually or asexually, and have life cycles that range from simple to complex. Filamentous fungi refer to those that grow as multicelluar colonies (mushrooms and molds). [NIH] Fungicides, Industrial: Chemicals that kill or inhibit the growth of fungi in agricultural applications, on wood, plastics, or other materials, in swimming pools, etc. [NIH] Fungistatic: Inhibiting the growth of fungi. [EU] Fungus: A general term used to denote a group of eukaryotic protists, including mushrooms, yeasts, rusts, moulds, smuts, etc., which are characterized by the absence of chlorophyll and by the presence of a rigid cell wall composed of chitin, mannans, and sometimes cellulose. They are usually of simple morphological form or show some reversible cellular specialization, such as the formation of pseudoparenchymatous tissue in the fruiting body of a mushroom. The dimorphic fungi grow, according to environmental conditions, as moulds or yeasts. [EU] 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] Galenical: 1. Usually cap: of or relating to Galen or his medical principles or method. 2. Constituting a galenical. [EU] Gallbladder: The pear-shaped organ that sits below the liver. Bile is concentrated and stored in the gallbladder. [NIH] Gamma Rays: Very powerful and penetrating, high-energy electromagnetic radiation of shorter wavelength than that of x-rays. They are emitted by a decaying nucleus, usually between 0.01 and 10 MeV. They are also called nuclear x-rays. [NIH] Ganglia: Clusters of multipolar neurons surrounded by a capsule of loosely organized connective tissue located outside the central nervous system. [NIH] 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] Gasoline: Volative flammable fuel (liquid hydrocarbons) derived from crude petroleum by processes such as distillation reforming, polymerization, etc. [NIH]
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Gastric: Having to do with the stomach. [NIH] Gastric Juices: Liquids produced in the stomach to help break down food and kill bacteria. [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]
Gastritis: Inflammation of the stomach. [EU] Gastroduodenal: Pertaining to or communicating with the stomach and duodenum, as a gastroduodenal fistula. [EU] Gastrointestinal: Refers to the stomach and intestines. [NIH] Gastrointestinal tract: The stomach and intestines. [NIH] Gelatin: A product formed from skin, white connective tissue, or bone collagen. It is used as a protein food adjuvant, plasma substitute, hemostatic, suspending agent in pharmaceutical preparations, and in the manufacturing of capsules and suppositories. [NIH] Gelatinases: A class of enzymes that catalyzes the degradation of gelatin by acting on the peptide bonds. EC 3.4.24.-. [NIH] Gels: Colloids with a solid continuous phase and liquid as the dispersed phase; gels may be unstable when, due to temperature or other cause, the solid phase liquifies; the resulting colloid is called a sol. [NIH] Gelsolin: A 90-kD protein produced by macrophages that severs actin filaments and forms a cap on the newly exposed filament end. Gelsolin is activated by calcium ions and participates in the assembly and disassembly of actin, thereby increasing the motility of some cells. [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 Amplification: A selective increase in the number of copies of a gene coding for a specific protein without a proportional increase in other genes. It occurs naturally via the excision of a copy of the repeating sequence from the chromosome and its extrachromosomal replication in a plasmid, or via the production of an RNA transcript of the entire repeating sequence of ribosomal RNA followed by the reverse transcription of the molecule to produce an additional copy of the original DNA sequence. Laboratory techniques have been introduced for inducing disproportional replication by unequal crossing over, uptake of DNA from lysed cells, or generation of extrachromosomal sequences from rolling circle replication. [NIH] Gene Expression: The phenotypic manifestation of a gene or genes by the processes of gene action. [NIH] Gene Expression Profiling: The determination of the pattern of genes expressed i.e., transcribed, under specific circumstances or in a specific cell. [NIH] Gene Fusion: Fusion of structural genes to analyze protein behavior or fusion of regulatory sequences with structural genes to determine mechanisms of regulation. [NIH] Gene Products, pol: Retroviral proteins coded by the pol gene. They are usually synthesized as a protein precursor (polyproteins) and later cleaved into final products that include reverse transcriptase, endonuclease/integrase, and viral protease. Sometimes they are
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synthesized as a gag-pol fusion protein. Pol is short for polymerase, the enzyme class of reverse transcriptase. [NIH] Gene Targeting: The integration of exogenous DNA into the genome of an organism at sites where its expression can be suitably controlled. This integration occurs as a result of homologous recombination. [NIH] Gene Therapy: The introduction of new genes into cells for the purpose of treating disease by restoring or adding gene expression. Techniques include insertion of retroviral vectors, transfection, homologous recombination, and injection of new genes into the nuclei of single cell embryos. The entire gene therapy process may consist of multiple steps. The new genes may be introduced into proliferating cells in vivo (e.g., bone marrow) or in vitro (e.g., fibroblast cultures) and the modified cells transferred to the site where the gene expression is required. Gene therapy may be particularly useful for treating enzyme deficiency diseases, hemoglobinopathies, and leukemias and may also prove useful in restoring drug sensitivity, particularly for leukemia. [NIH] Gene-modified: Cells that have been altered to contain different genetic material than they originally contained. [NIH] Genetic Code: The specifications for how information, stored in nucleic acid sequence (base sequence), is translated into protein sequence (amino acid sequence). The start, stop, and order of amino acids of a protein is specified by consecutive triplets of nucleotides called codons (codon). [NIH] Genetic Engineering: Directed modification of the gene complement of a living organism by such techniques as altering the DNA, substituting genetic material by means of a virus, transplanting whole nuclei, transplanting cell hybrids, etc. [NIH] Genetic Markers: A phenotypically recognizable genetic trait which can be used to identify a genetic locus, a linkage group, or a recombination event. [NIH] Genetic testing: Analyzing DNA to look for a genetic alteration that may indicate an increased risk for developing a specific disease or disorder. [NIH] Genetic transcription: The process by which the genetic information encoded in the gene, represented as a linear sequence of deoxyribonucleotides, is copied into an exactly complementary sequence of ribonucleotides known as messenger RNA. [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] Genomics: The systematic study of the complete DNA sequences (genome) of organisms. [NIH]
Genotype: The genetic constitution of the individual; the characterization of the genes. [NIH] Germ Cells: The reproductive cells in multicellular organisms. [NIH] Gestation: The period of development of the young in viviparous animals, from the time of fertilization of the ovum until birth. [EU] Giardiasis: An infection of the small intestine caused by the flagellated protozoan Giardia lamblia. It is spread via contaminated food and water and by direct person-to-person contact. [NIH] Gingival Recession: The exposure of root surface by an apical shift in the position of the gingiva. [NIH] Gingivitis: Inflammation of the gingivae. Gingivitis associated with bony changes is
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referred to as periodontitis. Called also oulitis and ulitis. [EU] Gland: An organ that produces and releases one or more substances for use in the body. Some glands produce fluids that affect tissues or organs. Others produce hormones or participate in blood production. [NIH] Glioma: A cancer of the brain that comes from glial, or supportive, cells. [NIH] Glomerular: Pertaining to or of the nature of a glomerulus, especially a renal glomerulus. [EU]
Glomerulus: A tiny set of looping blood vessels in the nephron where blood is filtered in the kidney. [NIH] Glossitis: Inflammation of the tongue. [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] Glucose Intolerance: A pathological state in which the fasting plasma glucose level is less than 140 mg per deciliter and the 30-, 60-, or 90-minute plasma glucose concentration following a glucose tolerance test exceeds 200 mg per deciliter. This condition is seen frequently in diabetes mellitus but also occurs with other diseases. [NIH] Glucuronic Acid: Derivatives of uronic acid found throughout the plant and animal kingdoms. They detoxify drugs and toxins by conjugating with them to form glucuronides in the liver which are more water-soluble metabolites that can be easily eliminated from the body. [NIH] Glutamate: Excitatory neurotransmitter of the brain. [NIH] Glutamic Acid: A non-essential amino acid naturally occurring in the L-form. Glutamic acid (glutamate) is the most common excitatory neurotransmitter in the central nervous system. [NIH]
Gluten: The protein of wheat and other grains which gives to the dough its tough elastic character. [EU] Glycerol: A trihydroxy sugar alcohol that is an intermediate in carbohydrate and lipid metabolism. It is used as a solvent, emollient, pharmaceutical agent, and sweetening agent. [NIH]
Glycerophospholipids: Derivatives of phosphatidic acid in which the hydrophobic regions are composed of two fatty acids and a polar alcohol is joined to the C-3 position of glycerol through a phosphodiester bond. They are named according to their polar head groups, such as phosphatidylcholine and phosphatidylethanolamine. [NIH] Glycine: A non-essential amino acid. It is found primarily in gelatin and silk fibroin and used therapeutically as a nutrient. It is also a fast inhibitory neurotransmitter. [NIH] Glycogen: A sugar stored in the liver and muscles. It releases glucose into the blood when cells need it for energy. Glycogen is the chief source of stored fuel in the body. [NIH] Glycoprotein: A protein that has sugar molecules attached to it. [NIH] Glycosaminoglycan: A type of long, unbranched polysaccharide molecule. Glycosaminoglycans are major structural components of cartilage and are also found in the cornea of the eye. [NIH]
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Glycosidic: Formed by elimination of water between the anomeric hydroxyl of one sugar and a hydroxyl of another sugar molecule. [NIH] Glycosylation: The chemical or biochemical addition of carbohydrate or glycosyl groups to other chemicals, especially peptides or proteins. Glycosyl transferases are used in this biochemical reaction. [NIH] Goblet Cells: Cells of the epithelial lining that produce and secrete mucins. [NIH] Goiter: Enlargement of the thyroid gland. [NIH] Gonad: A sex organ, such as an ovary or a testicle, which produces the gametes in most multicellular animals. [NIH] Gonadal: Pertaining to a gonad. [EU] Gonorrhea: Acute infectious disease characterized by primary invasion of the urogenital tract. The etiologic agent, Neisseria gonorrhoeae, was isolated by Neisser in 1879. [NIH] Gonorrhoea: Infection due to Neisseria gonorrhoeae transmitted sexually in most cases, but also by contact with infected exudates in neonatal children at birth, or by infants in households with infected inhabitants. It is marked in males by urethritis with pain and purulent discharge, but is commonly asymptomatic in females, although it may extend to produce suppurative salpingitis, oophoritis, tubo-ovarian abscess, and peritonitis. Bacteraemia occurs in both sexes, resulting in cutaneous lesions, arthritis, and rarely meningitis or endocarditis. Formerly called blennorrhagia and blennorrhoea. [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] GP41: 41-kD HIV transmembrane envelope glycoprotein which mediates the fusion of the viral membrane with the membrane of the target cell. [NIH] Grade: The grade of a tumor depends on how abnormal the cancer cells look under a microscope and how quickly the tumor is likely to grow and spread. Grading systems are different for each type of cancer. [NIH] Grading: A system for classifying cancer cells in terms of how abnormal they appear when examined under a microscope. The objective of a grading system is to provide information about the probable growth rate of the tumor and its tendency to spread. The systems used to grade tumors vary with each type of cancer. Grading plays a role in treatment decisions. [NIH]
Graft: Healthy skin, bone, or other tissue taken from one part of the body and used to replace diseased or injured tissue removed from another part of the body. [NIH] Graft Rejection: An immune response with both cellular and humoral components, directed against an allogeneic transplant, whose tissue antigens are not compatible with those of the recipient. [NIH] Gram-negative: Losing the stain or decolorized by alcohol in Gram's method of staining, a primary characteristic of bacteria having a cell wall composed of a thin layer of peptidoglycan covered by an outer membrane of lipoprotein and lipopolysaccharide. [EU] Gram-Negative Bacteria: Bacteria which lose crystal violet stain but are stained pink when treated by Gram's method. [NIH] Gram-positive: Retaining the stain or resisting decolorization by alcohol in Gram's method of staining, a primary characteristic of bacteria whose cell wall is composed of a thick layer
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of peptidologlycan with attached teichoic acids. [EU] Gram-Positive Cocci: Coccus-shaped bacteria that retain the crystal violet stain when treated by Gram's method. [NIH] Granule: A small pill made from sucrose. [EU] Granulocytes: Leukocytes with abundant granules in the cytoplasm. They are divided into three groups: neutrophils, eosinophils, and basophils. [NIH] Granuloma: A relatively small nodular inflammatory lesion containing grouped mononuclear phagocytes, caused by infectious and noninfectious agents. [NIH] Granuloma Inguinale: Anogenital ulcers caused by Calymmatobacterium granulomatis as distinguished from lymphogranuloma inguinale (see lymphogranuloma venereum) caused by Chlamydia trachomatis. Diagnosis is made by demonstration of typical intracellular Donovan bodies in crushed-tissue smears. [NIH] Granulosa Cells: Cells of the membrana granulosa lining the vesicular ovarian follicle which become luteal cells after ovulation. [NIH] Grasses: A large family, Gramineae, of narrow-leaved herbaceous monocots. Many grasses produce highly allergenic pollens and are hosts to cattle parasites and toxic fungi. [NIH] Growth: The progressive development of a living being or part of an organism from its earliest stage to maturity. [NIH] Growth factors: Substances made by the body that function to regulate cell division and cell survival. Some growth factors are also produced in the laboratory and used in biological therapy. [NIH] Guanylate Cyclase: An enzyme that catalyzes the conversion of GTP to 3',5'-cyclic GMP and pyrophosphate. It also acts on ITP and dGTP. (From Enzyme Nomenclature, 1992) EC 4.6.1.2. [NIH] Gyrase: An enzyme that causes negative supercoiling of E. coli DNA during replication. [NIH]
Habitual: Of the nature of a habit; according to habit; established by or repeated by force of habit, customary. [EU] Hair Cells: Mechanoreceptors located in the organ of Corti that are sensitive to auditory stimuli and in the vestibular apparatus that are sensitive to movement of the head. In each case the accessory sensory structures are arranged so that appropriate stimuli cause movement of the hair-like projections (stereocilia and kinocilia) which relay the information centrally in the nervous system. [NIH] Hair follicles: Shafts or openings on the surface of the skin through which hair grows. [NIH] Half-Life: The time it takes for a substance (drug, radioactive nuclide, or other) to lose half of its pharmacologic, physiologic, or radiologic activity. [NIH] Halitosis: An offensive, foul breath odor resulting from a variety of causes such as poor oral hygiene, dental or oral infections, or the ingestion of certain foods. [NIH] Haploid: An organism with one basic chromosome set, symbolized by n; the normal condition of gametes in diploids. [NIH] Haptens: Small antigenic determinants capable of eliciting an immune response only when coupled to a carrier. Haptens bind to antibodies but by themselves cannot elicit an antibody response. [NIH] Headache: Pain in the cranial region that may occur as an isolated and benign symptom or as a manifestation of a wide variety of conditions including subarachnoid hemorrhage; craniocerebral trauma; central nervous system infections; intracranial hypertension; and
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other disorders. In general, recurrent headaches that are not associated with a primary disease process are referred to as headache disorders (e.g., migraine). [NIH] Health Education: Education that increases the awareness and favorably influences the attitudes and knowledge relating to the improvement of health on a personal or community basis. [NIH] Heart failure: Loss of pumping ability by the heart, often accompanied by fatigue, breathlessness, and excess fluid accumulation in body tissues. [NIH] Heartburn: Substernal pain or burning sensation, usually associated with regurgitation of gastric juice into the esophagus. [NIH] Hematopoiesis: The development and formation of various types of blood cells. [NIH] Hematopoietic Stem Cells: Progenitor cells from which all blood cells derive. [NIH] Heme: The color-furnishing portion of hemoglobin. It is found free in tissues and as the prosthetic group in many hemeproteins. [NIH] Hemoglobin: One of the fractions of glycosylated hemoglobin A1c. Glycosylated hemoglobin is formed when linkages of glucose and related monosaccharides bind to hemoglobin A and its concentration represents the average blood glucose level over the previous several weeks. HbA1c levels are used as a measure of long-term control of plasma glucose (normal, 4 to 6 percent). In controlled diabetes mellitus, the concentration of glycosylated hemoglobin A is within the normal range, but in uncontrolled cases the level may be 3 to 4 times the normal conentration. Generally, complications are substantially lower among patients with Hb levels of 7 percent or less than in patients with HbA1c levels of 9 percent or more. [NIH] Hemoglobin A: Normal adult human hemoglobin. The globin moiety consists of two alpha and two beta chains. [NIH] Hemoglobinopathies: A group of inherited disorders characterized by structural alterations within the hemoglobin molecule. [NIH] Hemolysins: Substances, usually of biological origin, that destroy blood cells; they may be antibodies or other immunologic factors, toxins, enzymes, etc.; hemotoxins are toxic to blood in general, including the clotting mechanism; hematotoxins may refer to the hematopoietic system. [NIH] Hemopneumothorax: Collection of air and blood in the pleural cavity. [NIH] Hemorrhage: Bleeding or escape of blood from a vessel. [NIH] Hemorrhoids: Varicosities of the hemorrhoidal venous plexuses. [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]
Hemothorax: Hemorrhage within the pleural cavity. [NIH] Heparin: Heparinic acid. A highly acidic mucopolysaccharide formed of equal parts of sulfated D-glucosamine and D-glucuronic acid with sulfaminic bridges. The molecular weight ranges from six to twenty thousand. Heparin occurs in and is obtained from liver, lung, mast cells, etc., of vertebrates. Its function is unknown, but it is used to prevent blood clotting in vivo and vitro, in the form of many different salts. [NIH] Hepatic: Refers to the liver. [NIH] Hepatobiliary: Pertaining to the liver and the bile or the biliary ducts. [EU] Herbicide: A chemical that kills plants. [NIH]
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Hereditary: Of, relating to, or denoting factors that can be transmitted genetically from one generation to another. [NIH] Heredity: 1. The genetic transmission of a particular quality or trait from parent to offspring. 2. The genetic constitution of an individual. [EU] Herpes: Any inflammatory skin disease caused by a herpesvirus and characterized by the formation of clusters of small vesicles. When used alone, the term may refer to herpes simplex or to herpes zoster. [EU] Herpes Zoster: Acute vesicular inflammation. [NIH] Herpetiformis: Duhring's disease a recurring, inflammatory disease of the skin of unknown etiology characterized by erythematous, papular, pustular, or vesicular lesions which tend to group and are accompanied by itching and burning. [NIH] Heterodimers: Zippered pair of nonidentical proteins. [NIH] Heterogeneity: The property of one or more samples or populations which implies that they are not identical in respect of some or all of their parameters, e. g. heterogeneity of variance. [NIH]
Heterotrophic: Pertaining to organisms that are consumers and dependent on other organisms for their source of energy (food). [NIH] Hippocampus: A curved elevation of gray matter extending the entire length of the floor of the temporal horn of the lateral ventricle (Dorland, 28th ed). The hippocampus, subiculum, and dentate gyrus constitute the hippocampal formation. Sometimes authors include the entorhinal cortex in the hippocampal formation. [NIH] Histamine: 1H-Imidazole-4-ethanamine. A depressor amine derived by enzymatic decarboxylation of histidine. It is a powerful stimulant of gastric secretion, a constrictor of bronchial smooth muscle, a vasodilator, and also a centrally acting neurotransmitter. [NIH] Histidine: An essential amino acid important in a number of metabolic processes. It is required for the production of histamine. [NIH] Histocompatibility: The degree of antigenic similarity between the tissues of different individuals, which determines the acceptance or rejection of allografts. [NIH] Histology: The study of tissues and cells under a microscope. [NIH] Histone Deacetylase: Hydrolyzes N-acetyl groups on histones. [NIH] Homeobox: Distinctive sequence of DNA bases. [NIH] Homeostasis: The processes whereby the internal environment of an organism tends to remain balanced and stable. [NIH] Homodimer: Protein-binding "activation domains" always combine with identical proteins. [NIH]
Homogeneous: Consisting of or composed of similar elements or ingredients; of a uniform quality throughout. [EU] Homologous: Corresponding in structure, position, origin, etc., as (a) the feathers of a bird and the scales of a fish, (b) antigen and its specific antibody, (c) allelic chromosomes. [EU] 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] Horny layer: The superficial layer of the epidermis containing keratinized cells. [NIH] Host: Any animal that receives a transplanted graft. [NIH]
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Humoral: Of, relating to, proceeding from, or involving a bodily humour - now often used of endocrine factors as opposed to neural or somatic. [EU] Humour: 1. A normal functioning fluid or semifluid of the body (as the blood, lymph or bile) especially of vertebrates. 2. A secretion that is itself an excitant of activity (as certain hormones). [EU] Hybrid: Cross fertilization between two varieties or, more usually, two species of vines, see also crossing. [NIH] Hybridization: The genetic process of crossbreeding to produce a hybrid. Hybrid nucleic acids can be formed by nucleic acid hybridization of DNA and RNA molecules. Protein hybridization allows for hybrid proteins to be formed from polypeptide chains. [NIH] 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] Hydrochloric Acid: A strong corrosive acid that is commonly used as a laboratory reagent. It is formed by dissolving hydrogen chloride in water. Gastric acid is the hydrochloric acid component of gastric juice. [NIH] Hydrogen: The first chemical element in the periodic table. It has the atomic symbol H, atomic number 1, and atomic weight 1. It exists, under normal conditions, as a colorless, odorless, tasteless, diatomic gas. Hydrogen ions are protons. Besides the common H1 isotope, hydrogen exists as the stable isotope deuterium and the unstable, radioactive isotope tritium. [NIH] Hydrogen Peroxide: A strong oxidizing agent used in aqueous solution as a ripening agent, bleach, and topical anti-infective. It is relatively unstable and solutions deteriorate over time unless stabilized by the addition of acetanilide or similar organic materials. [NIH] Hydrogenation: Specific method of reduction in which hydrogen is added to a substance by the direct use of gaseous hydrogen. [NIH] Hydrolysis: The process of cleaving a chemical compound by the addition of a molecule of water. [NIH] Hydrophilic: Readily absorbing moisture; hygroscopic; having strongly polar groups that readily interact with water. [EU] Hydrophobic: Not readily absorbing water, or being adversely affected by water, as a hydrophobic colloid. [EU] 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] Hydroxyurea: An antineoplastic agent that inhibits DNA synthesis through the inhibition of ribonucleoside diphosphate reductase. [NIH] Hypercalcemia: Abnormally high level of calcium in the blood. [NIH] Hyperglycemia: Abnormally high blood sugar. [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] Hyperthyroidism: Excessive functional activity of the thyroid gland. [NIH]
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Hypertrophy: General increase in bulk of a part or organ, not due to tumor formation, nor to an increase in the number of cells. [NIH] Hypoglycemia: Abnormally low blood sugar [NIH] 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] Hypoplasia: Incomplete development or underdevelopment of an organ or tissue. [EU] Hypoxic: Having too little oxygen. [NIH] Ibuprofen: A nonsteroidal anti-inflammatory agent with analgesic properties used in the therapy of rheumatism and arthritis. [NIH] Id: The part of the personality structure which harbors the unconscious instinctive desires and strivings of the individual. [NIH] Idiopathic: Describes a disease of unknown cause. [NIH] Iduronidase: An enzyme that hydrolyzes iduronosidic linkages in desulfated dermatan. Deficiency of this enzyme produces Hurler's syndrome. EC 3.2.1.76. [NIH] Ileum: The lower end of the small intestine. [NIH] Imidazole: C3H4N2. The ring is present in polybenzimidazoles. [NIH] Imipenem: Semisynthetic thienamycin that has a wide spectrum of antibacterial activity against gram-negative and gram-positive aerobic and anaerobic bacteria, including many multiresistant strains. It is stable to beta-lactamases. Clinical studies have demonstrated high efficacy in the treatment of infections of various body systems. Its effectiveness is enhanced when it is administered in combination with cilastatin, a renal dipeptidase inhibitor. [NIH] Immortal: Stage when the mother cell and its descendants will multiply indefinitely. [NIH] Immune function: Production and action of cells that fight disease or infection. [NIH] Immune response: The activity of the immune system against foreign substances (antigens). [NIH]
Immune Sera: Serum that contains antibodies. It is obtained from an animal that has been immunized either by antigen injection or infection with microorganisms containing the antigen. [NIH] Immune system: The organs, cells, and molecules responsible for the recognition and disposal of foreign ("non-self") material which enters the body. [NIH] Immunity: Nonsusceptibility to the invasive or pathogenic microorganisms or to the toxic effect of antigenic substances. [NIH]
effects
of
foreign
Immunization: Deliberate stimulation of the host's immune response. Active immunization involves administration of antigens or immunologic adjuvants. Passive immunization involves administration of immune sera or lymphocytes or their extracts (e.g., transfer factor, immune RNA) or transplantation of immunocompetent cell producing tissue (thymus or bone marrow). [NIH] Immunoblotting: Immunologic methods for isolating and quantitatively measuring immunoreactive substances. When used with immune reagents such as monoclonal antibodies, the process is known generically as western blot analysis (blotting, western). [NIH]
Immunocompromised: Having a weakened immune system caused by certain diseases or treatments. [NIH]
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Immunodeficiency: The decreased ability of the body to fight infection and disease. [NIH] Immunodiffusion: Technique involving the diffusion of antigen or antibody through a semisolid medium, usually agar or agarose gel, with the result being a precipitin reaction. [NIH]
Immunoelectrophoresis: A technique that combines protein electrophoresis and double immunodiffusion. In this procedure proteins are first separated by gel electrophoresis (usually agarose), then made visible by immunodiffusion of specific antibodies. A distinct elliptical precipitin arc results for each protein detectable by the antisera. [NIH] Immunofluorescence: A technique for identifying molecules present on the surfaces of cells or in tissues using a highly fluorescent substance coupled to a specific antibody. [NIH] Immunogenic: Producing immunity; evoking an immune response. [EU] Immunoglobulin: A protein that acts as an antibody. [NIH] Immunohistochemistry: Histochemical localization of immunoreactive substances using labeled antibodies as reagents. [NIH] Immunologic: The ability of the antibody-forming system to recall a previous experience with an antigen and to respond to a second exposure with the prompt production of large amounts of antibody. [NIH] Immunologic Factors: Biologically active substances whose activities affect or play a role in the functioning of the immune system. [NIH] Immunology: The study of the body's immune system. [NIH] Immunosuppressant: An agent capable of suppressing immune responses. [EU] 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] Immunosuppressive therapy: Therapy used to decrease the body's immune response, such as drugs given to prevent transplant rejection. [NIH] Immunotherapy: Manipulation of the host's immune system in treatment of disease. It includes both active and passive immunization as well as immunosuppressive therapy to prevent graft rejection. [NIH] Impairment: In the context of health experience, an impairment is any loss or abnormality of psychological, physiological, or anatomical structure or function. [NIH] 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] Incidental: 1. Small and relatively unimportant, minor; 2. Accompanying, but not a major
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part of something; 3. (To something) Liable to occur because of something or in connection with something (said of risks, responsibilities, .) [EU] Incision: A cut made in the body during surgery. [NIH] Incisor: Anything adapted for cutting; any one of the four front teeth in each jaw. [NIH] Incubation: The development of an infectious disease from the entrance of the pathogen to the appearance of clinical symptoms. [EU] Incubation period: The period of time likely to elapse between exposure to the agent of the disease and the onset of clinical symptoms. [NIH] Indicative: That indicates; that points out more or less exactly; that reveals fairly clearly. [EU] Indigestion: Poor digestion. Symptoms include heartburn, nausea, bloating, and gas. Also called dyspepsia. [NIH] Indomethacin: A non-steroidal anti-inflammatory agent (NSAID) that inhibits the enzyme cyclooxygenase necessary for the formation of prostaglandins and other autacoids. It also inhibits the motility of polymorphonuclear leukocytes. [NIH] Induction: The act or process of inducing or causing to occur, especially the production of a specific morphogenetic effect in the developing embryo through the influence of evocators or organizers, or the production of anaesthesia or unconsciousness by use of appropriate agents. [EU] Infancy: The period of complete dependency prior to the acquisition of competence in walking, talking, and self-feeding. [NIH] Infant, Newborn: An infant during the first month after birth. [NIH] Infarction: A pathological process consisting of a sudden insufficient blood supply to an area, which results in necrosis of that area. It is usually caused by a thrombus, an embolus, or a vascular torsion. [NIH] Infection: 1. Invasion and multiplication of microorganisms in body tissues, which may be clinically unapparent or result in local cellular injury due to competitive metabolism, toxins, intracellular replication, or antigen-antibody response. The infection may remain localized, subclinical, and temporary if the body's defensive mechanisms are effective. A local infection may persist and spread by extension to become an acute, subacute, or chronic clinical infection or disease state. A local infection may also become systemic when the microorganisms gain access to the lymphatic or vascular system. 2. An infectious disease. [EU]
Infiltration: The diffusion or accumulation in a tissue or cells of substances not normal to it or in amounts of the normal. Also, the material so accumulated. [EU] Inflammation: A pathological process characterized by injury or destruction of tissues caused by a variety of cytologic and chemical reactions. It is usually manifested by typical signs of pain, heat, redness, swelling, and loss of function. [NIH] Inflammatory bowel disease: A general term that refers to the inflammation of the colon and rectum. Inflammatory bowel disease includes ulcerative colitis and Crohn's disease. [NIH]
Influenza: An acute viral infection involving the respiratory tract. It is marked by inflammation of the nasal mucosa, the pharynx, and conjunctiva, and by headache and severe, often generalized, myalgia. [NIH] Infusion: A method of putting fluids, including drugs, into the bloodstream. Also called intravenous infusion. [NIH] Ingestion: Taking into the body by mouth [NIH]
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Inguinal: Pertaining to the inguen, or groin. [EU] Inhalation: The drawing of air or other substances into the lungs. [EU] Inhibin: Glyceroprotein hormone produced in the seminiferous tubules by the Sertoli cells in the male and by the granulosa cells in the female follicles. The hormone inhibits FSH and LH synthesis and secretion by the pituitary cells thereby affecting sexual maturation and fertility. [NIH] Initiation: Mutation induced by a chemical reactive substance causing cell changes; being a step in a carcinogenic process. [NIH] Inlay: In dentistry, a filling first made to correspond with the form of a dental cavity and then cemented into the cavity. [NIH] Inner ear: The labyrinth, comprising the vestibule, cochlea, and semicircular canals. [NIH] Inorganic: Pertaining to substances not of organic origin. [EU] Inotropic: Affecting the force or energy of muscular contractions. [EU] Insecticides: Pesticides designed to control insects that are harmful to man. The insects may be directly harmful, as those acting as disease vectors, or indirectly harmful, as destroyers of crops, food products, or textile fabrics. [NIH] Insertional: A technique in which foreign DNA is cloned into a restriction site which occupies a position within the coding sequence of a gene in the cloning vector molecule. Insertion interrupts the gene's sequence such that its original function is no longer expressed. [NIH] Insight: The capacity to understand one's own motives, to be aware of one's own psychodynamics, to appreciate the meaning of symbolic behavior. [NIH] Instillation: . [EU] Insulator: Material covering the metal conductor of the lead. It is usually polyurethane or silicone. [NIH] Insulin: A protein hormone secreted by beta cells of the pancreas. Insulin plays a major role in the regulation of glucose metabolism, generally promoting the cellular utilization of glucose. It is also an important regulator of protein and lipid metabolism. Insulin is used as a drug to control insulin-dependent diabetes mellitus. [NIH] Insulin-dependent diabetes mellitus: A disease characterized by high levels of blood glucose resulting from defects in insulin secretion, insulin action, or both. Autoimmune, genetic, and environmental factors are involved in the development of type I diabetes. [NIH] Integrase: An enzyme that inserts DNA into the host genome. It is encoded by the pol gene of retroviruses and also by temperate bacteriophages, the best known being bacteriophage lambda. EC 2.7.7.-. [NIH] Integrins: A family of transmembrane glycoproteins consisting of noncovalent heterodimers. They interact with a wide variety of ligands including extracellular matrix glycoproteins, complement, and other cells, while their intracellular domains interact with the cytoskeleton. The integrins consist of at least three identified families: the cytoadhesin receptors, the leukocyte adhesion receptors, and the very-late-antigen receptors. Each family contains a common beta-subunit combined with one or more distinct alpha-subunits. These receptors participate in cell-matrix and cell-cell adhesion in many physiologically important processes, including embryological development, hemostasis, thrombosis, wound healing, immune and nonimmune defense mechanisms, and oncogenic transformation. [NIH] Intensive Care: Advanced and highly specialized care provided to medical or surgical patients whose conditions are life-threatening and require comprehensive care and constant
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monitoring. It is usually administered in specially equipped units of a health care facility. [NIH]
Interferon: A biological response modifier (a substance that can improve the body's natural response to disease). Interferons interfere with the division of cancer cells and can slow tumor growth. There are several types of interferons, including interferon-alpha, -beta, and gamma. These substances are normally produced by the body. They are also made in the laboratory for use in treating cancer and other diseases. [NIH] Interferon-alpha: One of the type I interferons produced by peripheral blood leukocytes or lymphoblastoid cells when exposed to live or inactivated virus, double-stranded RNA, or 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-10: Factor that is a coregulator of mast cell growth. It is produced by T-cells and B-cells and shows extensive homology with the Epstein-Barr virus BCRFI gene. [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] Interleukins: Soluble factors which stimulate growth-related activities of leukocytes as well as other cell types. They enhance cell proliferation and differentiation, DNA synthesis, secretion of other biologically active molecules and responses to immune and inflammatory stimuli. [NIH] Intermediate Filaments: Cytoplasmic filaments intermediate in diameter (about 10 nanometers) between the microfilaments and the microtubules. They may be composed of any of a number of different proteins and form a ring around the cell nucleus. [NIH] Intermittent: Occurring at separated intervals; having periods of cessation of activity. [EU] Internal Capsule: White matter pathway, flanked by nuclear masses, consisting of both afferent and efferent fibers projecting between the cerebral cortex and the brainstem. It consists of three distinct parts: an anterior limb, posterior limb, and genu. [NIH] Internal Medicine: A medical specialty concerned with the diagnosis and treatment of diseases of the internal organ systems of adults. [NIH] 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] 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, types I, II and III. EC 3.4.24.7. [NIH] Intervertebral: Situated between two contiguous vertebrae. [EU] Intestinal: Having to do with the intestines. [NIH] Intestinal Flora: The bacteria, yeasts, and fungi that grow normally in the intestines. [NIH] Intestinal Mucosa: The surface lining of the intestines where the cells absorb nutrients. [NIH] Intestinal Neoplasms: Tumors or cancer of the intestines. [NIH]
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Intestine: A long, tube-shaped organ in the abdomen that completes the process of digestion. There is both a large intestine and a small intestine. Also called the bowel. [NIH] Intracellular: Inside a cell. [NIH] Intracellular Membranes: Membranes of subcellular structures. [NIH] Intramuscular: IM. Within or into muscle. [NIH] Intravenous: IV. Into a vein. [NIH] Intrinsic: Situated entirely within or pertaining exclusively to a part. [EU] Invasive: 1. Having the quality of invasiveness. 2. Involving puncture or incision of the skin or insertion of an instrument or foreign material into the body; said of diagnostic techniques. [EU]
Invertebrates: Animals that have no spinal column. [NIH] Involuntary: Reaction occurring without intention or volition. [NIH] Involution: 1. A rolling or turning inward. 2. One of the movements involved in the gastrulation of many animals. 3. A retrograde change of the entire body or in a particular organ, as the retrograde changes in the female genital organs that result in normal size after delivery. 4. The progressive degeneration occurring naturally with advancing age, resulting in shrivelling of organs or tissues. [EU] Iodoquinol: One of the halogenated 8-quinolinols widely used as an intestinal antiseptic, especially as an antiamebic agent. It is also used topically in other infections and may cause CNS and eye damage. It is known by very many similar trade names worldwide. [NIH] Ion Channels: Gated, ion-selective glycoproteins that traverse membranes. The stimulus for channel gating can be a membrane potential, drug, transmitter, cytoplasmic messenger, or a mechanical deformation. Ion channels which are integral parts of ionotropic neurotransmitter receptors are not included. [NIH] Ion Transport: The movement of ions across energy-transducing cell membranes. Transport can be active or passive. Passive ion transport (facilitated diffusion) derives its energy from the concentration gradient of the ion itself and allows the transport of a single solute in one direction (uniport). Active ion transport is usually coupled to an energy-yielding chemical or photochemical reaction such as ATP hydrolysis. This form of primary active transport is called an ion pump. Secondary active transport utilizes the voltage and ion gradients produced by the primary transport to drive the cotransport of other ions or molecules. These may be transported in the same (symport) or opposite (antiport) direction. [NIH] Ionizing: Radiation comprising charged particles, e. g. electrons, protons, alpha-particles, etc., having sufficient kinetic energy to produce ionization by collision. [NIH] Ionophores: Chemical agents that increase the permeability of biological or artificial lipid membranes to specific ions. Most ionophores are relatively small organic molecules that act as mobile carriers within membranes or coalesce to form ion permeable channels across membranes. Many are antibiotics, and many act as uncoupling agents by short-circuiting the proton gradient across mitochondrial membranes. [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] Iris: The most anterior portion of the uveal layer, separating the anterior chamber from the posterior. It consists of two layers - the stroma and the pigmented epithelium. Color of the iris depends on the amount of melanin in the stroma on reflection from the pigmented epithelium. [NIH]
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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] Irrigation: The washing of a body cavity or surface by flowing solution which is inserted and then removed. Any drug in the irrigation solution may be absorbed. [NIH] Irritants: Drugs that act locally on cutaneous or mucosal surfaces to produce inflammation; those that cause redness due to hyperemia are rubefacients; those that raise blisters are vesicants and those that penetrate sebaceous glands and cause abscesses are pustulants; tear gases and mustard gases are also irritants. [NIH] Ischemia: Deficiency of blood in a part, due to functional constriction or actual obstruction of a blood vessel. [EU] Ischemic stroke: A condition in which the blood supply to part of the brain is cut off. Also called "plug-type" strokes. Blocked arteries starve areas of the brain controlling sight, speech, sensation, and movement so that these functions are partially or completely lost. Ischemic stroke is the most common type of stroke, accounting for 80 percent of all strokes. Most ischemic strokes are caused by a blood clot called a thrombus, which blocks blood flow in the arteries feeding the brain, usually the carotid artery in the neck, the major vessel bringing blood to the brain. When it becomes blocked, the risk of stroke is very high. [NIH] Islet: Cell producing insulin in pancreas. [NIH] Joint: The point of contact between elements of an animal skeleton with the parts that surround and support it. [NIH] Kb: A measure of the length of DNA fragments, 1 Kb = 1000 base pairs. The largest DNA fragments are up to 50 kilobases long. [NIH] Keratan Sulfate: A sulfated mucopolysaccharide initially isolated from bovine cornea. At least two types are known. Type I, found mostly in the cornea, contains D-galactose and Dglucosamine-6-O-sulfate as the repeating unit; type II, found in skeletal tissues, contains Dgalactose and D-galactosamine-6-O-sulfate as the repeating unit. [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] Keratitis: Inflammation of the cornea. [NIH] Kerato: Prefix indicating relationship to the cornea. [NIH] Keratoconjunctivitis: Simultaneous inflammation of the cornea and conjunctiva. [NIH] Keratoconjunctivitis Sicca: Drying and inflammation of the conjunctiva as a result of insufficient lacrimal secretion. When found in association with xerostomia and polyarthritis,
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it is called Sjogren's syndrome. [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 Disease: Any one of several chronic conditions that are caused by damage to the cells of the kidney. People who have had diabetes for a long time may have kidney damage. Also called nephropathy. [NIH] Kinetic: Pertaining to or producing motion. [EU] Labile: 1. Gliding; moving from point to point over the surface; unstable; fluctuating. 2. Chemically unstable. [EU] Lacrimal: Pertaining to the tears. [EU] Lacrimal gland: The small almond-shaped structure that produces tears; located just above the outer corner of the eye. [NIH] Lactation: The period of the secretion of milk. [EU] Laminin: Large, noncollagenous glycoprotein with antigenic properties. It is localized in the basement membrane lamina lucida and functions to bind epithelial cells to the basement membrane. Evidence suggests that the protein plays a role in tumor invasion. [NIH] Large Intestine: The part of the intestine that goes from the cecum to the rectum. The large intestine absorbs water from stool and changes it from a liquid to a solid form. The large intestine is 5 feet long and includes the appendix, cecum, colon, and rectum. Also called colon. [NIH] Larynx: An irregularly shaped, musculocartilaginous tubular structure, lined with mucous membrane, located at the top of the trachea and below the root of the tongue and the hyoid bone. It is the essential sphincter guarding the entrance into the trachea and functioning secondarily as the organ of voice. [NIH] Latent: Phoria which occurs at one distance or another and which usually has no troublesome effect. [NIH] Lavage: A cleaning of the stomach and colon. Uses a special drink and enemas. [NIH] Laxative: An agent that acts to promote evacuation of the bowel; a cathartic or purgative. [EU]
Lead Poisoning: Disease caused by the gradual accumulation of a significant body burden of lead. [NIH] Lens: The transparent, double convex (outward curve on both sides) structure suspended between the aqueous and vitreous; helps to focus light on the retina. [NIH] 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] Leucine: An essential branched-chain amino acid important for hemoglobin formation. [NIH] Leukemia: Cancer of blood-forming tissue. [NIH] Leukocytes: White blood cells. These include granular leukocytes (basophils, eosinophils, and neutrophils) as well as non-granular leukocytes (lymphocytes and monocytes). [NIH] Leukotrienes: A family of biologically active compounds derived from arachidonic acid by
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oxidative metabolism through the 5-lipoxygenase pathway. They participate in host defense reactions and pathophysiological conditions such as immediate hypersensitivity and inflammation. They have potent actions on many essential organs and systems, including the cardiovascular, pulmonary, and central nervous system as well as the gastrointestinal tract and the immune system. [NIH] Levodopa: The naturally occurring form of dopa and the immediate precursor of dopamine. Unlike dopamine itself, it can be taken orally and crosses the blood-brain barrier. It is rapidly taken up by dopaminergic neurons and converted to dopamine. It is used for the treatment of parkinsonism and is usually given with agents that inhibit its conversion to dopamine outside of the central nervous system. [NIH] Libido: The psychic drive or energy associated with sexual instinct in the broad sense (pleasure and love-object seeking). It may also connote the psychic energy associated with instincts in general that motivate behavior. [NIH] Library Services: Services offered to the library user. They include reference and circulation. [NIH]
Lidocaine: A local anesthetic and cardiac depressant used as an antiarrhythmia agent. Its actions are more intense and its effects more prolonged than those of procaine but its duration of action is shorter than that of bupivacaine or prilocaine. [NIH] Life cycle: The successive stages through which an organism passes from fertilized ovum or spore to the fertilized ovum or spore of the next generation. [NIH] Ligament: A band of fibrous tissue that connects bones or cartilages, serving to support and strengthen joints. [EU] Ligands: A RNA simulation method developed by the MIT. [NIH] Lincomycin: (2S-trans)-Methyl 6,8-dideoxy-6-(((1-methyl-4-propyl-2pyrrolidinyl)carbonyl)amino)-1-thio-D-erythro-alpha-D-galacto-octopyranoside. An antibiotic produced by Streptomyces lincolnensis var. lincolnensis. It has been used in the treatment of staphylococcal, streptococcal, and Bacteroides fragilis infections. [NIH] Linkage: The tendency of two or more genes in the same chromosome to remain together from one generation to the next more frequently than expected according to the law of independent assortment. [NIH] Lip: Either of the two fleshy, full-blooded margins of the mouth. [NIH] Lipase: An enzyme of the hydrolase class that catalyzes the reaction of triacylglycerol and water to yield diacylglycerol and a fatty acid anion. It is produced by glands on the tongue and by the pancreas and initiates the digestion of dietary fats. (From Dorland, 27th ed) EC 3.1.1.3. [NIH] Lipid: Fat. [NIH] Lipid Peroxidation: Peroxidase catalyzed oxidation of lipids using hydrogen peroxide as an electron acceptor. [NIH] Lipophilic: Having an affinity for fat; pertaining to or characterized by lipophilia. [EU] Lipopolysaccharide: Substance consisting of polysaccaride and lipid. [NIH] Lipoprotein: Any of the lipid-protein complexes in which lipids are transported in the blood; lipoprotein particles consist of a spherical hydrophobic core of triglycerides or cholesterol esters surrounded by an amphipathic monolayer of phospholipids, cholesterol, and apolipoproteins; the four principal classes are high-density, low-density, and very-lowdensity lipoproteins and chylomicrons. [EU] Liposarcoma: A rare cancer of the fat cells. [NIH]
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Liposomal: A drug preparation that contains the active drug in very tiny fat particles. This fat-encapsulated drug is absorbed better, and its distribution to the tumor site is improved. [NIH]
Liver: A large, glandular organ located in the upper abdomen. The liver cleanses the blood and aids in digestion by secreting bile. [NIH] Liver cancer: A disease in which malignant (cancer) cells are found in the tissues of the liver. [NIH]
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] Long-Term Care: Care over an extended period, usually for a chronic condition or disability, requiring periodic, intermittent, or continuous care. [NIH] Loop: A wire usually of platinum bent at one end into a small loop (usually 4 mm inside diameter) and used in transferring microorganisms. [NIH] Low-density lipoprotein: Lipoprotein that contains most of the cholesterol in the blood. LDL carries cholesterol to the tissues of the body, including the arteries. A high level of LDL increases the risk of heart disease. LDL typically contains 60 to 70 percent of the total serum cholesterol and both are directly correlated with CHD risk. [NIH] Lucida: An instrument, invented by Wollaton, consisting essentially of a prism or a mirror through which an object can be viewed so as to appear on a plane surface seen in direct view and on which the outline of the object may be traced. [NIH] Lumen: The cavity or channel within a tube or tubular organ. [EU] Luminescence: The property of giving off light without emitting a corresponding degree of heat. It includes the luminescence of inorganic matter or the bioluminescence of human matter, invertebrates and other living organisms. For the luminescence of bacteria, bacterial luminescence is available. [NIH] Lupus: A form of cutaneous tuberculosis. It is seen predominantly in women and typically involves the nasal, buccal, and conjunctival mucosa. [NIH] Luteal Phase: The period of the menstrual cycle that begins with ovulation and ends with menstruation. [NIH] Lutein Cells: The cells of the corpus luteum which are derived from the granulosa cells and the theca cells of the Graafian follicle. [NIH] Lymph: The almost colorless fluid that travels through the lymphatic system and carries cells that help fight infection and disease. [NIH] Lymph node: A rounded mass of lymphatic tissue that is surrounded by a capsule of connective tissue. Also known as a lymph gland. Lymph nodes are spread out along lymphatic vessels and contain many lymphocytes, which filter the lymphatic fluid (lymph). [NIH]
Lymphatic: The tissues and organs, including the bone marrow, spleen, thymus, and lymph nodes, that produce and store cells that fight infection and disease. [NIH] Lymphatic system: The tissues and organs that produce, store, and carry white blood cells that fight infection and other diseases. This system includes the bone marrow, spleen, thymus, lymph nodes and a network of thin tubes that carry lymph and white blood cells.
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These tubes branch, like blood vessels, into all the tissues of the body. [NIH] Lymphoblastic: One of the most aggressive types of non-Hodgkin lymphoma. [NIH] Lymphoblasts: Interferon produced predominantly by leucocyte cells. [NIH] Lymphocyte: A white blood cell. Lymphocytes have a number of roles in the immune system, including the production of antibodies and other substances that fight infection and diseases. [NIH] Lymphogranuloma Venereum: Subacute inflammation of the inguinal lymph glands caused by certain immunotypes of Chlamydia trachomatis. It is a sexually transmitted disease in the U.S. but is more widespread in developing countries. It is distinguished from granuloma venereum (granuloma inguinale), which is caused by Calymmatobacterium granulomatis. [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] Lymphoproliferative: Disorders characterized by proliferation of lymphoid tissue, general or unspecified. [NIH] Lysine: An essential amino acid. It is often added to animal feed. [NIH] Lytic: 1. Pertaining to lysis or to a lysin. 2. Producing lysis. [EU] Macroglia: A type of neuroglia composed of astrocytes. [NIH] Macrolides: A group of organic compounds that contain a macrocyclic lactone ring linked glycosidically to one or more sugar moieties. [NIH] Macrophage: A type of white blood cell that surrounds and kills microorganisms, removes dead cells, and stimulates the action of other immune system cells. [NIH] Macula: A stain, spot, or thickening. Often used alone to refer to the macula retinae. [EU] Macula Lutea: An oval area in the retina, 3 to 5 mm in diameter, usually located temporal to the superior pole of the eye and slightly below the level of the optic disk. [NIH] Macular Degeneration: Degenerative changes in the macula lutea of the retina. [NIH] Major Histocompatibility Complex: The genetic region which contains the loci of genes which determine the structure of the serologically defined (SD) and lymphocyte-defined (LD) transplantation antigens, genes which control the structure of the immune responseassociated (Ia) antigens, the immune response (Ir) genes which control the ability of an animal to respond immunologically to antigenic stimuli, and genes which determine the structure and/or level of the first four components of complement. [NIH] Malabsorption: Impaired intestinal absorption of nutrients. [EU] Malabsorption syndrome: A group of symptoms such as gas, bloating, abdominal pain, and diarrhea resulting from the body's inability to properly absorb nutrients. [NIH] Malaise: A vague feeling of bodily discomfort. [EU] Malaria: A protozoan disease caused in humans by four species of the genus Plasmodium (P. falciparum (malaria, falciparum), P. vivax (malaria, vivax), P. ovale, and P. malariae) and transmitted by the bite of an infected female mosquito of the genus Anopheles. Malaria is endemic in parts of Asia, Africa, Central and South America, Oceania, and certain Caribbean islands. It is characterized by extreme exhaustion associated with paroxysms of high fever, sweating, shaking chills, and anemia. Malaria in animals is caused by other species of plasmodia. [NIH] Malaria, Falciparum: Malaria caused by Plasmodium falciparum. This is the severest form
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of malaria and is associated with the highest levels of parasites in the blood. This disease is characterized by irregularly recurring febrile paroxysms that in extreme cases occur with acute cerebral, renal, or gastrointestinal manifestations. [NIH] Malaria, Vivax: Malaria caused by Plasmodium vivax. This form of malaria is less severe than malaria, falciparum, but there is a higher probability for relapses to occur. Febrile paroxysms often occur every other day. [NIH] Malignant: Cancerous; a growth with a tendency to invade and destroy nearby tissue and spread to other parts of the body. [NIH] Malignant tumor: A tumor capable of metastasizing. [NIH] Malnutrition: A condition caused by not eating enough food or not eating a balanced diet. [NIH]
Mammary: Pertaining to the mamma, or breast. [EU] Mammogram: An x-ray of the breast. [NIH] Mandible: The largest and strongest bone of the face constituting the lower jaw. It supports the lower teeth. [NIH] Manifest: Being the part or aspect of a phenomenon that is directly observable : concretely expressed in behaviour. [EU] Mannans: Polysaccharides consisting of mannose units. [NIH] Mastectomy: Surgery to remove the breast (or as much of the breast tissue as possible). [NIH] Materials Testing: The testing of materials and devices, especially those used for implants, prostheses, sutures, adhesives, etc., for hardness, strength, durability, safety, and efficacy. [NIH]
Matrix metalloproteinase: A member of a group of enzymes that can break down proteins, such as collagen, that are normally found in the spaces between cells in tissues (i.e., extracellular matrix proteins). Because these enzymes need zinc or calcium atoms to work properly, they are called metalloproteinases. Matrix metalloproteinases are involved in wound healing, angiogenesis, and tumor cell metastasis. [NIH] Maxillary: Pertaining to the maxilla : the irregularly shaped bone that with its fellow forms the upper jaw. [EU] 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] Mefloquine: A phospholipid-interacting antimalarial drug (antimalarials). It is very effective against Plasmodium falciparum with very few side effects. [NIH] Megaloblastic: A large abnormal red blood cell appearing in the blood in pernicious anaemia. [EU] Meibomian: A series of simple, branched, alveolar, sebaceous glands, located in the tarso of the eyelids, whose ducts empty into the eyelid margins in line with and lateral to the lacrimal puncta. [NIH]
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Meibomian Glands: The sebaceous glands situated on the inner surface of the eyelids between the tarsal plates and conjunctiva. [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] Melanosomes: Melanin-containing organelles found in melanocytes and melanophores. [NIH]
Membrane: A very thin layer of tissue that covers a surface. [NIH] Membrane Fusion: The adherence of cell membranes, intracellular membranes, or artifical membrane models of either to each other or to viruses, parasites, or interstitial particles through a variety of chemical and physical processes. [NIH] Membrane 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] Menopause: Permanent cessation of menstruation. [NIH] Menstrual Cycle: The period of the regularly recurring physiologic changes in the endometrium occurring during the reproductive period in human females and some primates and culminating in partial sloughing of the endometrium (menstruation). [NIH] Menstruation: The normal physiologic discharge through the vagina of blood and mucosal tissues from the nonpregnant uterus. [NIH] Mental: Pertaining to the mind; psychic. 2. (L. mentum chin) pertaining to the chin. [EU] Mental Disorders: Psychiatric illness or diseases manifested by breakdowns in the adaptational process expressed primarily as abnormalities of thought, feeling, and behavior producing either distress or impairment of function. [NIH] Mental Health: The state wherein the person is well adjusted. [NIH] Mental Retardation: Refers to sub-average general intellectual functioning which originated
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during the developmental period and is associated with impairment in adaptive behavior. [NIH]
Mercury: A silver metallic element that exists as a liquid at room temperature. It has the atomic symbol Hg (from hydrargyrum, liquid silver), atomic number 80, and atomic weight 200.59. Mercury is used in many industrial applications and its salts have been employed therapeutically as purgatives, antisyphilitics, disinfectants, and astringents. It can be absorbed through the skin and mucous membranes which leads to mercury poisoning. Because of its toxicity, the clinical use of mercury and mercurials is diminishing. [NIH] Mesenchymal: Refers to cells that develop into connective tissue, blood vessels, and lymphatic tissue. [NIH] Mesoderm: The middle germ layer of the embryo. [NIH] Meta-Analysis: A quantitative method of combining the results of independent studies (usually drawn from the published literature) and synthesizing summaries and conclusions which may be used to evaluate therapeutic effectiveness, plan new studies, etc., with application chiefly in the areas of research and medicine. [NIH] Metabolite: Any substance produced by metabolism or by a metabolic process. [EU] 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] Metaplasia: A condition in which there is a change of one adult cell type to another similar adult cell type. [NIH] Metastasis: The spread of cancer from one part of the body to another. Tumors formed from cells that have spread are called "secondary tumors" and contain cells that are like those in the original (primary) tumor. The plural is metastases. [NIH] Metastatic: Having to do with metastasis, which is the spread of cancer from one part of the body to another. [NIH] Metastatic cancer: Cancer that has spread from the place in which it started to other parts of the body. [NIH] Methicillin Resistance: Non-susceptibility of a microbe to the action of methicillin, a semisynthetic penicillin derivative. [NIH] Methionine: A sulfur containing essential amino acid that is important in many body functions. It is a chelating agent for heavy metals. [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] Metronidazole: Antiprotozoal used in amebiasis, trichomoniasis, giardiasis, and as treponemacide in livestock. It has also been proposed as a radiation sensitizer for hypoxic cells. According to the Fourth Annual Report on Carcinogens (NTP 85-002, 1985, p133), this substance may reasonably be anticipated to be a carcinogen (Merck, 11th ed). [NIH] MI: Myocardial infarction. Gross necrosis of the myocardium as a result of interruption of the blood supply to the area; it is almost always caused by atherosclerosis of the coronary arteries, upon which coronary thrombosis is usually superimposed. [NIH] Mice Minute Virus: The type species of parvovirus prevalent in mouse colonies and found as a contaminant of many transplanted tumors or leukemias. [NIH]
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Microbe: An organism which cannot be observed with the naked eye; e. g. unicellular animals, lower algae, lower fungi, bacteria. [NIH] Microbiological: Pertaining to microbiology : the science that deals with microorganisms, including algae, bacteria, fungi, protozoa and viruses. [EU] Microbiology: The study of microorganisms such as fungi, bacteria, algae, archaea, and viruses. [NIH] Microcalcifications: Tiny deposits of calcium in the breast that cannot be felt but can be detected on a mammogram. A cluster of these very small specks of calcium may indicate that cancer is present. [NIH] Microfilaments: The smallest of the cytoskeletal filaments. They are composed chiefly of actin. [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] Micronutrients: Essential dietary elements or organic compounds that are required in only small quantities for normal physiologic processes to occur. [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] Microtubule-Associated Proteins: High molecular weight proteins found in the microtubules of the cytoskeletal system. Under certain conditions they are required for tubulin assembly into the microtubules and stabilize the assembled microtubules. [NIH] Microtubules: Slender, cylindrical filaments found in the cytoskeleton of plant and animal cells. They are composed of the protein tubulin. [NIH] Middle Cerebral Artery: The largest and most complex of the cerebral arteries. Branches of the middle cerebral artery supply the insular region, motor and premotor areas, and large regions of the association cortex. [NIH] Mifepristone: A progestational and glucocorticoid hormone antagonist. Its inhibition of progesterone induces bleeding during the luteal phase and in early pregnancy by releasing endogenous prostaglandins from the endometrium or decidua. As a glucocorticoid receptor antagonist, the drug has been used to treat hypercortisolism in patients with nonpituitary Cushing syndrome. [NIH] Migration: The systematic movement of genes between populations of the same species, geographic race, or variety. [NIH] Milliliter: A measure of volume for a liquid. A milliliter is approximately 950-times smaller than a quart and 30-times smaller than a fluid ounce. A milliliter of liquid and a cubic centimeter (cc) of liquid are the same. [NIH] Millimeter: A measure of length. A millimeter is approximately 26-times smaller than an inch. [NIH]
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Mineralization: The action of mineralizing; the state of being mineralized. [EU] 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] Minocycline: A semisynthetic staphylococcus infections. [NIH]
antibiotic
effective
against
tetracycline-resistant
Miscible: Susceptible of being mixed. [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] 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] Mobility: Capability of movement, of being moved, or of flowing freely. [EU] Mobilization: The process of making a fixed part or stored substance mobile, as by separating a part from surrounding structures to make it accessible for an operative procedure or by causing release into the circulation for body use of a substance stored in the body. [EU] Mode of Transmission: Hepatitis A [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] Modification: A change in an organism, or in a process in an organism, that is acquired from its own activity or environment. [NIH] Modulator: A specific inductor that brings out characteristics peculiar to a definite region. [EU]
Molecular: Of, pertaining to, or composed of molecules : a very small mass of matter. [EU] Molecular Probes: A group of atoms or molecules attached to other molecules or cellular structures and used in studying the properties of these molecules and structures. Radioactive DNA or RNA sequences are used in molecular genetics to detect the presence of a complementary sequence by molecular hybridization. [NIH] Molecule: A chemical made up of two or more atoms. The atoms in a molecule can be the same (an oxygen molecule has two oxygen atoms) or different (a water molecule has two hydrogen atoms and one oxygen atom). Biological molecules, such as proteins and DNA, can be made up of many thousands of atoms. [NIH] Monitor: An apparatus which automatically records such physiological signs as respiration, pulse, and blood pressure in an anesthetized patient or one undergoing surgical or other procedures. [NIH] Monoclonal: An antibody produced by culturing a single type of cell. It therefore consists of a single species of immunoglobulin molecules. [NIH] Monoclonal antibodies: Laboratory-produced substances that can locate and bind to cancer cells wherever they are in the body. Many monoclonal antibodies are used in cancer detection or therapy; each one recognizes a different protein on certain cancer cells. Monoclonal antibodies can be used alone, or they can be used to deliver drugs, toxins, or
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radioactive material directly to a tumor. [NIH] Monocyte: A type of white blood cell. [NIH] Mononuclear: A cell with one nucleus. [NIH] Morphogenesis: The development of the form of an organ, part of the body, or organism. [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 Neurons: Neurons which activate muscle cells. [NIH] Mucins: A secretion containing mucopolysaccharides and protein that is the chief constituent of mucus. [NIH] Mucociliary: Pertaining to or affecting the mucus membrane and hairs (including eyelashes, nose hair, .): mucociliary clearing: the clearance of mucus by ciliary movement ( particularly in the respiratory system). [EU] Mucocutaneous: Pertaining to or affecting the mucous membrane and the skin. [EU] Mucosa: A mucous membrane, or tunica mucosa. [EU] Mucositis: A complication of some cancer therapies in which the lining of the digestive system becomes inflamed. Often seen as sores in the mouth. [NIH] Mucus: The viscous secretion of mucous membranes. It contains mucin, white blood cells, water, inorganic salts, and exfoliated cells. [NIH] Multiple sclerosis: A disorder of the central nervous system marked by weakness, numbness, a loss of muscle coordination, and problems with vision, speech, and bladder control. Multiple sclerosis is thought to be an autoimmune disease in which the body's immune system destroys myelin. Myelin is a substance that contains both protein and fat (lipid) and serves as a nerve insulator and helps in the transmission of nerve signals. [NIH] Muscle Contraction: A process leading to shortening and/or development of tension in muscle tissue. Muscle contraction occurs by a sliding filament mechanism whereby actin filaments slide inward among the myosin filaments. [NIH] Muscle Fibers: Large single cells, either cylindrical or prismatic in shape, that form the basic unit of muscle tissue. They consist of a soft contractile substance enclosed in a tubular sheath. [NIH] Muscular Dystrophies: A general term for a group of inherited disorders which are characterized by progressive degeneration of skeletal muscles. [NIH] Mustard Gas: Severe irritant and vesicant of skin, eyes, and lungs. It may cause blindness and lethal lung edema and was formerly used as a war gas. The substance has been proposed as a cytostatic and for treatment of psoriasis. It has been listed as a known carcinogen in the Fourth Annual Report on Carcinogens (NTP-85-002, 1985) (Merck, 11th ed). [NIH] 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
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chromosomes. [NIH] Mutate: To change the genetic material of a cell. Then changes (mutations) can be harmful, beneficial, or have no effect. [NIH] Myalgia: Pain in a muscle or muscles. [EU] Mycoplasma: A genus of gram-negative, facultatively anaerobic bacteria bounded by a plasma membrane only. Its organisms are parasites and pathogens, found on the mucous membranes of humans, animals, and birds. [NIH] Mycosis: Any disease caused by a fungus. [EU] Mycotic: Pertaining to a mycosis; caused by fungi. [EU] Myelin: The fatty substance that covers and protects nerves. [NIH] Myelogenous: Produced by, or originating in, the bone marrow. [NIH] Myocardial infarction: Gross necrosis of the myocardium as a result of interruption of the blood supply to the area; it is almost always caused by atherosclerosis of the coronary arteries, upon which coronary thrombosis is usually superimposed. [NIH] Myocardial Ischemia: A disorder of cardiac function caused by insufficient blood flow to the muscle tissue of the heart. The decreased blood flow may be due to narrowing of the coronary arteries (coronary arteriosclerosis), to obstruction by a thrombus (coronary thrombosis), or less commonly, to diffuse narrowing of arterioles and other small vessels within the heart. Severe interruption of the blood supply to the myocardial tissue may result in necrosis of cardiac muscle (myocardial infarction). [NIH] Myocardial Reperfusion: Generally, restoration of blood supply to heart tissue which is ischemic due to decrease in normal blood supply. The decrease may result from any source including atherosclerotic obstruction, narrowing of the artery, or surgical clamping. Reperfusion can be induced to treat ischemia. Methods include chemical dissolution of an occluding thrombus, administration of vasodilator drugs, angioplasty, catheterization, and artery bypass graft surgery. However, it is thought that reperfusion can itself further damage the ischemic tissue, causing myocardial reperfusion injury. [NIH] Myocardial Reperfusion Injury: Functional, metabolic, or structural changes in ischemic heart muscle thought to result from reperfusion to the ischemic areas. Changes can be fatal to muscle cells and may include edema with explosive cell swelling and disintegration, sarcolemma disruption, fragmentation of mitochondria, contraction band necrosis, enzyme washout, and calcium overload. Other damage may include hemorrhage and ventricular arrhythmias. One possible mechanism of damage is thought to be oxygen free radicals. Treatment currently includes the introduction of scavengers of oxygen free radicals, and injury is thought to be prevented by warm blood cardioplegic infusion prior to reperfusion. [NIH]
Myocarditis: Inflammation of the myocardium; inflammation of the muscular walls of the heart. [EU] Myocardium: The muscle tissue of the heart composed of striated, involuntary muscle known as cardiac muscle. [NIH] Myofibrils: Highly organized bundles of actin, myosin, and other proteins in the cytoplasm of skeletal and cardiac muscle cells that contract by a sliding filament mechanism. [NIH] Myosin: Chief protein in muscle and the main constituent of the thick filaments of muscle fibers. In conjunction with actin, it is responsible for the contraction and relaxation of muscles. [NIH] Myotonia: Prolonged failure of muscle relaxation after contraction. This may occur after voluntary contractions, muscle percussion, or electrical stimulation of the muscle. Myotonia
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is a characteristic feature of myotonic disorders. [NIH] Naevus: A circumscribed area of pigmentation or vascularization, usually in the form of a congenital benign neoplasm occurring in the skin or in various ocular tissues. [NIH] Naive: Used to describe an individual who has never taken a certain drug or class of drugs (e. g., AZT-naive, antiretroviral-naive), or to refer to an undifferentiated immune system cell. [NIH] Naproxen: An anti-inflammatory agent with analgesic and antipyretic properties. Both the acid and its sodium salt are used in the treatment of rheumatoid arthritis and other rheumatic or musculoskeletal disorders, dysmenorrhea, and acute gout. [NIH] Nasal Cavity: The proximal portion of the respiratory passages on either side of the nasal septum, lined with ciliated mucosa, extending from the nares to the pharynx. [NIH] Nasal Mucosa: The mucous membrane lining the nasal cavity. [NIH] Nasal Septum: The partition separating the two nasal cavities in the midplane, composed of cartilaginous, membranous and bony parts. [NIH] Nausea: An unpleasant sensation in the stomach usually accompanied by the urge to vomit. Common causes are early pregnancy, sea and motion sickness, emotional stress, intense pain, food poisoning, and various enteroviruses. [NIH] NCI: National Cancer Institute. NCI, part of the National Institutes of Health of the United States Department of Health and Human Services, is the federal government's principal agency for cancer research. NCI conducts, coordinates, and funds cancer research, training, health information dissemination, and other programs with respect to the cause, diagnosis, prevention, and treatment of cancer. Access the NCI Web site at http://cancer.gov. [NIH] Necrosis: A pathological process caused by the progressive degradative action of enzymes that is generally associated with severe cellular trauma. It is characterized by mitochondrial swelling, nuclear flocculation, uncontrolled cell lysis, and ultimately cell death. [NIH] Need: A state of tension or dissatisfaction felt by an individual that impels him to action toward a goal he believes will satisfy the impulse. [NIH] Neocortex: The largest portion of the cerebral cortex. It is composed of neurons arranged in six layers. [NIH] Neomycin: Antibiotic complex produced by Streptomyces fradiae. It is composed of neomycins A, B, and C. It acts by inhibiting translation during protein synthesis. [NIH] Neonatal: Pertaining to the first four weeks after birth. [EU] Neoplasia: Abnormal and uncontrolled cell growth. [NIH] Neoplasm: A new growth of benign or malignant tissue. [NIH] Neoplastic: Pertaining to or like a neoplasm (= any new and abnormal growth); pertaining to neoplasia (= the formation of a neoplasm). [EU] Nephritis: Inflammation of the kidney; a focal or diffuse proliferative or destructive process which may involve the glomerulus, tubule, or interstitial renal tissue. [EU] Nephron: A tiny part of the kidneys. Each kidney is made up of about 1 million nephrons, which are the working units of the kidneys, removing wastes and extra fluids from the blood. [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]
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Nephrotic Syndrome: Clinical association of heavy proteinuria, hypoalbuminemia, and generalized edema. [NIH] Nephrotoxic: Toxic or destructive to kidney cells. [EU] Nerve: A cordlike structure of nervous tissue that connects parts of the nervous system with other tissues of the body and conveys nervous impulses to, or away from, these tissues. [NIH] Nerve Degeneration: Loss of functional activity and trophic degeneration of nerve axons and their terminal arborizations following the destruction of their cells of origin or interruption of their continuity with these cells. The pathology is characteristic of neurodegenerative diseases. Often the process of nerve degeneration is studied in research on neuroanatomical localization and correlation of the neurophysiology of neural pathways. [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] Neural Crest: A strip of specialized ectoderm flanking each side of the embryonal neural plate, which after the closure of the neural tube, forms a column of isolated cells along the dorsal aspect of the neural tube. Most of the cranial and all of the spinal sensory ganglion cells arise by differentiation of neural crest cells. [NIH] Neural Pathways: Neural tracts connecting one part of the nervous system with another. [NIH]
Neuroblastoma: Cancer that arises in immature nerve cells and affects mostly infants and children. [NIH] Neurodegenerative Diseases: Hereditary and sporadic conditions which are characterized by progressive nervous system dysfunction. These disorders are often associated with atrophy of the affected central or peripheral nervous system structures. [NIH] Neurofibrillary Tangles: Abnormal structures located in various parts of the brain and composed of dense arrays of paired helical filaments (neurofilaments and microtubules). These double helical stacks of transverse subunits are twisted into left-handed ribbon-like filaments that likely incorporate the following proteins: (1) the intermediate filaments: medium- and high-molecular-weight neurofilaments; (2) the microtubule-associated proteins map-2 and tau; (3) actin; and (4) ubiquitin. As one of the hallmarks of Alzheimer disease, the neurofibrillary tangles eventually occupy the whole of the cytoplasm in certain classes of cell in the neocortex, hippocampus, brain stem, and diencephalon. The number of these tangles, as seen in post mortem histology, correlates with the degree of dementia during life. Some studies suggest that tangle antigens leak into the systemic circulation both in the course of normal aging and in cases of Alzheimer disease. [NIH] Neurofilaments: Bundle of neuronal fibers. [NIH] Neurologic: Having to do with nerves or the nervous system. [NIH] Neuronal: Pertaining to a neuron or neurons (= conducting cells of the nervous system). [EU] Neuronal Plasticity: The capacity of the nervous system to change its reactivity as the result of successive activations. [NIH] Neurons: The basic cellular units of nervous tissue. Each neuron consists of a body, an axon,
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and dendrites. Their purpose is to receive, conduct, and transmit impulses in the nervous system. [NIH] Neurophysiology: The scientific discipline concerned with the physiology of the nervous system. [NIH] Neuroretinitis: Inflammation of the optic nerve head and adjacent retina. [NIH] Neurosciences: The scientific disciplines concerned with the embryology, anatomy, physiology, biochemistry, pharmacology, etc., of the nervous sytem. [NIH] Neurotoxic: Poisonous or destructive to nerve tissue. [EU] Neurotoxicity: The tendency of some treatments to cause damage to the nervous system. [NIH]
Neurotoxin: A substance that is poisonous to nerve tissue. [NIH] 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] 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] Nevus: A benign growth on the skin, such as a mole. A mole is a cluster of melanocytes and surrounding supportive tissue that usually appears as a tan, brown, or flesh-colored spot on the skin. The plural of nevus is nevi (NEE-vye). [NIH] Niacinamide: An important compound functioning as a component of the coenzyme NAD. Its primary significance is in the prevention and/or cure of blacktongue and pellagra. Most animals cannot manufacture this compound in amounts sufficient to prevent nutritional deficiency and it therefore must be supplemented through dietary intake. [NIH] Nifedipine: A potent vasodilator agent with calcium antagonistic action. It is a useful antianginal agent that also lowers blood pressure. The use of nifedipine as a tocolytic is being investigated. [NIH] Nitric Oxide: A free radical gas produced endogenously by a variety of mammalian cells. It is synthesized from arginine by a complex reaction, catalyzed by nitric oxide synthase. Nitric oxide is endothelium-derived relaxing factor. It is released by the vascular endothelium and mediates the relaxation induced by some vasodilators such as acetylcholine and bradykinin. It also inhibits platelet aggregation, induces disaggregation of aggregated platelets, and inhibits platelet adhesion to the vascular endothelium. Nitric oxide activates cytosolic guanylate cyclase and thus elevates intracellular levels of cyclic GMP. [NIH]
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] Nitrosamines: A class of compounds that contain a -NH2 and a -NO radical. Many members
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of this group have carcinogenic and mutagenic properties. [NIH] Nitrosation: Conversion into nitroso compounds. An example is the reaction of nitrites with amino compounds to form carcinogenic N-nitrosamines. [NIH] Norepinephrine: Precursor of epinephrine that is secreted by the adrenal medulla and is a widespread central and autonomic neurotransmitter. Norepinephrine is the principal transmitter of most postganglionic sympathetic fibers and of the diffuse projection system in the brain arising from the locus ceruleus. It is also found in plants and is used pharmacologically as a sympathomimetic. [NIH] Norfloxacin: Quinoline-derived synthetic antibacterial agent with a very broad spectrum of action. Oral administration yields highly bactericidal plasma, tissue, and urine levels. Norfloxacin inhibits bacterial DNA-gyrase and is used in gastrointestinal, eye, and urinary infections. [NIH] Nosocomial: Pertaining to or originating in the hospital, said of an infection not present or incubating prior to admittance to the hospital, but generally occurring 72 hours after admittance; the term is usually used to refer to patient disease, but hospital personnel may also acquire nosocomial infection. [EU] Nuclear: A test of the structure, blood flow, and function of the kidneys. The doctor injects a mildly radioactive solution into an arm vein and uses x-rays to monitor its progress through the kidneys. [NIH] Nuclei: A body of specialized protoplasm found in nearly all cells and containing the chromosomes. [NIH] Nucleic acid: Either of two types of macromolecule (DNA or RNA) formed by polymerization of nucleotides. Nucleic acids are found in all living cells and contain the information (genetic code) for the transfer of genetic information from one generation to the next. [NIH] Nucleic Acid Hybridization: The process whereby two single-stranded polynucleotides form a double-stranded molecule, with hydrogen bonding between the complementary bases in the two strains. [NIH] Nucleocapsid: A protein-nucleic acid complex which forms part or all of a virion. It consists of a capsid plus enclosed nucleic acid. Depending on the virus, the nucleocapsid may correspond to a naked core or be surrounded by a membranous envelope. [NIH] Nucleolus: A small dense body (sub organelle) within the nucleus of eukaryotic cells, visible by phase contrast and interference microscopy in live cells throughout interphase. Contains RNA and protein and is the site of synthesis of ribosomal RNA. [NIH] Nucleus: A body of specialized protoplasm found in nearly all cells and containing the chromosomes. [NIH] Nutritional Status: State of the body in relation to the consumption and utilization of nutrients. [NIH] Ocular: 1. Of, pertaining to, or affecting the eye. 2. Eyepiece. [EU] Odour: A volatile emanation that is perceived by the sense of smell. [EU] Ointments: Semisolid preparations used topically for protective emollient effects or as a vehicle for local administration of medications. Ointment bases are various mixtures of fats, waxes, animal and plant oils and solid and liquid hydrocarbons. [NIH] Omeprazole: A highly effective inhibitor of gastric acid secretion used in the therapy of gastric ulcers and Zollinger-Ellison syndrome. The drug inhibits the H(+)-K(+)-ATPase (H(+)-K(+)-exchanging ATPase) in a pH-dependent manner. This ATPase is considered the
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proton pump in the secretory membrane of the parietal cell. [NIH] Oncogene: A gene that normally directs cell growth. If altered, an oncogene can promote or allow the uncontrolled growth of cancer. Alterations can be inherited or caused by an environmental exposure to carcinogens. [NIH] Oncogenic: Chemical, viral, radioactive or other agent that causes cancer; carcinogenic. [NIH] Oncolysis: The destruction of or disposal by absorption of any neoplastic cells. [NIH] Oncolytic: Pertaining to, characterized by, or causing oncolysis (= the lysis or destruction of tumour cells). [EU] Oophoritis: Inflammation of an ovary. [NIH] Opacity: Degree of density (area most dense taken for reading). [NIH] Open Reading Frames: Reading frames where successive nucleotide triplets can be read as codons specifying amino acids and where the sequence of these triplets is not interrupted by stop codons. [NIH] Operon: The genetic unit consisting of a feedback system under the control of an operator gene, in which a structural gene transcribes its message in the form of mRNA upon blockade of a repressor produced by a regulator gene. Included here is the attenuator site of bacterial operons where transcription termination is regulated. [NIH] 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 Disk: The portion of the optic nerve seen in the fundus with the ophthalmoscope. It is formed by the meeting of all the retinal ganglion cell axons as they enter the optic nerve. [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] Optic nerve head: The circular area (disc) where the optic nerve connects to the retina. [NIH] Oral Health: The optimal state of the mouth and normal functioning of the organs of the mouth without evidence of disease. [NIH] Oral Hygiene: The practice of personal hygiene of the mouth. It includes the maintenance of oral cleanliness, tissue tone, and general preservation of oral health. [NIH] Organ Culture: The growth in aseptic culture of plant organs such as roots or shoots, beginning with organ primordia or segments and maintaining the characteristics of the organ. [NIH] Organelles: Specific particles of membrane-bound organized living substances present in eukaryotic cells, such as the mitochondria; the golgi apparatus; endoplasmic reticulum; lysomomes; plastids; and vacuoles. [NIH] Ori region: The point or region (origin) at which DNA replication begins in a bacterium or virus. Plasmids used in rec DNA research always contain an ori region, which gives very efficient initiation of replication. [NIH]
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Orofacial: Of or relating to the mouth and face. [EU] Osmosis: Tendency of fluids (e.g., water) to move from the less concentrated to the more concentrated side of a semipermeable membrane. [NIH] Osmotic: Pertaining to or of the nature of osmosis (= the passage of pure solvent from a solution of lesser to one of greater solute concentration when the two solutions are separated by a membrane which selectively prevents the passage of solute molecules, but is permeable to the solvent). [EU] Ossification: The formation of bone or of a bony substance; the conversion of fibrous tissue or of cartilage into bone or a bony substance. [EU] 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] Osteoblasts: Bone-forming cells which secrete an extracellular matrix. Hydroxyapatite crystals are then deposited into the matrix to form bone. [NIH] Osteoclasts: A large multinuclear cell associated with the absorption and removal of bone. An odontoclast, also called cementoclast, is cytomorphologically the same as an osteoclast and is involved in cementum resorption. [NIH] Osteocytes: Mature osteoblasts that have become embedded in the bone matrix. They occupy a small cavity, called lacuna, in the matrix and are connected to adjacent osteocytes via protoplasmic projections called canaliculi. [NIH] Osteogenesis: The histogenesis of bone including ossification. It occurs continuously but particularly in the embryo and child and during fracture repair. [NIH] Osteogenic sarcoma: A malignant tumor of the bone. Also called osteosarcoma. [NIH] Osteomalacia: A condition marked by softening of the bones (due to impaired mineralization, with excess accumulation of osteoid), with pain, tenderness, muscular weakness, anorexia, and loss of weight, resulting from deficiency of vitamin D and calcium. [EU]
Osteomyelitis: Inflammation of bone caused by a pyogenic organism. It may remain localized or may spread through the bone to involve the marrow, cortex, cancellous tissue, and periosteum. [EU] 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] Osteosarcoma: A cancer of the bone that affects primarily children and adolescents. Also called osteogenic sarcoma. [NIH] Ototoxic: Having a deleterious effect upon the eighth nerve, or upon the organs of hearing and balance. [EU] Outpatient: A patient who is not an inmate of a hospital but receives diagnosis or treatment in a clinic or dispensary connected with the hospital. [NIH] Ovarian Follicle: Spheroidal cell aggregation in the ovary containing an ovum. It consists of an external fibro-vascular coat, an internal coat of nucleated cells, and a transparent, albuminous fluid in which the ovum is suspended. [NIH] Ovaries: The pair of female reproductive glands in which the ova, or eggs, are formed. The ovaries are located in the pelvis, one on each side of the uterus. [NIH] Ovary: Either of the paired glands in the female that produce the female germ cells and
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secrete some of the female sex hormones. [NIH] Overexpress: An excess of a particular protein on the surface of a cell. [NIH] Ovum: A female germ cell extruded from the ovary at ovulation. [NIH] Oxazolidinones: Derivatives of oxazolidin-2-one. They represent an important class of synthetic antibiotic agents. [NIH] Oxidants: Oxidizing agents or electron-accepting molecules in chemical reactions in which electrons are transferred from one molecule to another (oxidation-reduction). In vivo, it appears that phagocyte-generated oxidants function as tumor promoters or cocarcinogens rather than as complete carcinogens perhaps because of the high levels of endogenous antioxidant defenses. It is also thought that oxidative damage in joints may trigger the autoimmune response that characterizes the persistence of the rheumatoid disease process. [NIH]
Oxidation: The act of oxidizing or state of being oxidized. Chemically it consists in the increase of positive charges on an atom or the loss of negative charges. Most biological oxidations are accomplished by the removal of a pair of hydrogen atoms (dehydrogenation) from a molecule. Such oxidations must be accompanied by reduction of an acceptor molecule. Univalent o. indicates loss of one electron; divalent o., the loss of two electrons. [EU]
Oxidation-Reduction: A chemical reaction in which an electron is transferred from one molecule to another. The electron-donating molecule is the reducing agent or reductant; the electron-accepting molecule is the oxidizing agent or oxidant. Reducing and oxidizing agents function as conjugate reductant-oxidant pairs or redox pairs (Lehninger, Principles of Biochemistry, 1982, p471). [NIH] Oxidative Phosphorylation: Electron transfer through the cytochrome system liberating free energy which is transformed into high-energy phosphate bonds. [NIH] Oxidative Stress: A disturbance in the prooxidant-antioxidant balance in favor of the former, leading to potential damage. Indicators of oxidative stress include damaged DNA bases, protein oxidation products, and lipid peroxidation products (Sies, Oxidative Stress, 1991, pxv-xvi). [NIH] Pachymeningitis: Inflammation of the dura mater of the brain, the spinal cord or the optic nerve. [NIH] Pactamycin: Antibiotic produced by Streptomyces pactum used as an antineoplastic agent. It is also used as a tool in biochemistry because it inhibits certain steps in protein synthesis. [NIH]
Paediatric: Of or relating to the care and medical treatment of children; belonging to or concerned with paediatrics. [EU] Palate: The structure that forms the roof of the mouth. It consists of the anterior hard palate and the posterior soft palate. [NIH] Palladium: A chemical element having an atomic weight of 106.4, atomic number of 46, and the symbol Pd. It is a white, ductile metal resembling platinum, and following it in abundance and importance of applications. It is used in dentistry in the form of gold, silver, and copper alloys. [NIH] Palliative: 1. Affording relief, but not cure. 2. An alleviating medicine. [EU] Palmitic Acid: A common saturated fatty acid found in fats and waxes including olive oil, palm oil, and body lipids. [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
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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] Pancreatitis: Acute or chronic inflammation of the pancreas, which may be asymptomatic or symptomatic, and which is due to autodigestion of a pancreatic tissue by its own enzymes. It is caused most often by alcoholism or biliary tract disease; less commonly it may be associated with hyperlipaemia, hyperparathyroidism, abdominal trauma (accidental or operative injury), vasculitis, or uraemia. [EU] Papilloma: A benign epithelial neoplasm which may arise from the skin, mucous membranes or glandular ducts. [NIH] Paracoccidioidomycosis: A mycosis affecting the skin, mucous membranes, lymph nodes, and internal organs. It is caused by Paracoccidioides brasiliensis. It is also called paracoccidioidal granuloma. Superficial resemblance of P. brasiliensis to Blastomyces brasiliensis (blastomyces) may cause misdiagnosis. [NIH] Paralysis: Loss of ability to move all or part of the body. [NIH] Paranasal Sinuses: Air-filled extensions of the respiratory part of the nasal cavity into the frontal, ethmoid, sphenoid, and maxillary cranial bones. They vary in size and form in different individuals and are lined by the ciliated mucous membranes of the nasal cavity. [NIH]
Parasite: An animal or a plant that lives on or in an organism of another species and gets at least some of its nutrition from that other organism. [NIH] Parasitic: Having to do with or being a parasite. A parasite is an animal or a plant that lives on or in an organism of another species and gets at least some of its nutrients from it. [NIH] Parasitization: The act or state of infestation by one or more parasites. [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] Parenteral: Not through the alimentary canal but rather by injection through some other route, as subcutaneous, intramuscular, intraorbital, intracapsular, intraspinal, intrasternal, intravenous, etc. [EU] Parietal: 1. Of or pertaining to the walls of a cavity. 2. Pertaining to or located near the parietal bone, as the parietal lobe. [EU] Parkinsonism: A group of neurological disorders characterized by hypokinesia, tremor, and muscular rigidity. [EU] Paromomycin: An oligosaccharide antibiotic produced by various Streptomyces. [NIH] Partial remission: The shrinking, but not complete disappearance, of a tumor in response to therapy. Also called partial response. [NIH] Particle: A tiny mass of material. [EU] Parturition: The act or process of given birth to a child. [EU] Parvovirus: A genus of the family Parvoviridae, subfamily Parvovirinae, infecting a variety of vertebrates including humans. Parvoviruses are responsible for a number of important diseases but also can be non-pathogenic in certain hosts. The type species is mice minute
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virus. [NIH] Patch: A piece of material used to cover or protect a wound, an injured part, etc.: a patch over the eye. [NIH] Pathogen: Any disease-producing microorganism. [EU] Pathogenesis: The cellular events and reactions that occur in the development of disease. [NIH]
Pathologic: 1. Indicative of or caused by a morbid condition. 2. Pertaining to pathology (= branch of medicine that treats the essential nature of the disease, especially the structural and functional changes in tissues and organs of the body caused by the disease). [EU] 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] Patient Education: The teaching or training of patients concerning their own health needs. [NIH]
Patient Selection: Criteria and standards used for the determination of the appropriateness of the inclusion of patients with specific conditions in proposed treatment plans and the criteria used for the inclusion of subjects in various clinical trials and other research protocols. [NIH] Pediatric Dentistry: The practice of dentistry concerned with the dental problems of children, proper maintenance, and treatment. The dental care may include the services provided by dental specialists. [NIH] Pelvic: Pertaining to the pelvis. [EU] Pelvic inflammatory disease: A bacteriological disease sometimes associated with intrauterine device (IUD) usage. [NIH] Pelvis: The lower part of the abdomen, located between the hip bones. [NIH] Pemphigus: Group of chronic blistering diseases characterized histologically by acantholysis and blister formation within the epidermis. [NIH] Penicillin: An antibiotic drug used to treat infection. [NIH] Penicillin Resistance: Nonsusceptibility of an organism to the action of penicillins. [NIH] Penicillinase: A beta-lactamase preferentially cleaving penicillins. (Dorland, 28th ed) EC 3.5.2.-. [NIH] Pepsin: An enzyme made in the stomach that breaks down proteins. [NIH] Peptic: Pertaining to pepsin or to digestion; related to the action of gastric juices. [EU] Peptic Ulcer: An ulceration of the mucous membrane of the esophagus, stomach or duodenum, caused by the action of the acid gastric juice. [NIH] Peptic Ulcer Hemorrhage: Bleeding from a peptic ulcer. [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] Perception: The ability quickly and accurately to recognize similarities and differences among presented objects, whether these be pairs of words, pairs of number series, or multiple sets of these or other symbols such as geometric figures. [NIH] Percutaneous: Performed through the skin, as injection of radiopacque material in
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radiological examination, or the removal of tissue for biopsy accomplished by a needle. [EU] Perfusion: Bathing an organ or tissue with a fluid. In regional perfusion, a specific area of the body (usually an arm or a leg) receives high doses of anticancer drugs through a blood vessel. Such a procedure is performed to treat cancer that has not spread. [NIH] Pericoronitis: Inflammation of the gingiva surrounding the crown of a tooth. [NIH] Perineum: The area between the anus and the sex organs. [NIH] Periodontal disease: Disease involving the supporting structures of the teeth (as the gums and periodontal membranes). [NIH] Periodontal disease: Disease involving the supporting structures of the teeth (as the gums and periodontal membranes). [NIH] Periodontal Ligament: Fibrous connective tissue surrounding the root of a tooth that separates it from and attaches it to the alveolar bone. [NIH] Periodontal Pocket: An abnormal extension of a gingival sulcus accompanied by the apical migration of the epithelial attachment and bone resorption. [NIH] Periodontitis: Inflammation of the periodontal membrane; also called periodontitis simplex. [NIH]
Perioral: Situated or occurring around the mouth. [EU] Peripheral Nerves: The nerves outside of the brain and spinal cord, including the autonomic, cranial, and spinal nerves. Peripheral nerves contain non-neuronal cells and connective tissue as well as axons. The connective tissue layers include, from the outside to the inside, the epineurium, the perineurium, and the endoneurium. [NIH] Peripheral Nervous System: The nervous system outside of the brain and spinal cord. The peripheral nervous system has autonomic and somatic divisions. The autonomic nervous system includes the enteric, parasympathetic, and sympathetic subdivisions. The somatic nervous system includes the cranial and spinal nerves and their ganglia and the peripheral sensory receptors. [NIH] 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] Peritonitis: Inflammation of the peritoneum; a condition marked by exudations in the peritoneum of serum, fibrin, cells, and pus. It is attended by abdominal pain and tenderness, constipation, vomiting, and moderate fever. [EU] Perivascular: Situated around a vessel. [EU] Peroxide: Chemical compound which contains an atom group with two oxygen atoms tied to each other. [NIH] PH: The symbol relating the hydrogen ion (H+) concentration or activity of a solution to that of a given standard solution. Numerically the pH is approximately equal to the negative logarithm of H+ concentration expressed in molarity. pH 7 is neutral; above it alkalinity
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increases and below it acidity increases. [EU] Phagocyte: An immune system cell that can surround and kill microorganisms and remove dead cells. Phagocytes include macrophages. [NIH] Phagocytosis: The engulfing of microorganisms, other cells, and foreign particles by phagocytic cells. [NIH] Phallic: Pertaining to the phallus, or penis. [EU] Pharmaceutical Preparations: Drugs intended for human or veterinary use, presented in their finished dosage form. Included here are materials used in the preparation and/or formulation of the finished dosage form. [NIH] Pharmaceutical Solutions: Homogeneous liquid preparations that contain one or more chemical substances dissolved, i.e., molecularly dispersed, in a suitable solvent or mixture of mutually miscible solvents. For reasons of their ingredients, method of preparation, or use, they do not fall into another group of products. [NIH] Pharmacokinetics: Dynamic and kinetic mechanisms of exogenous chemical and drug absorption, biotransformation, distribution, release, transport, uptake, and elimination as a function of dosage, and extent and rate of metabolic processes. It includes toxicokinetics, the pharmacokinetic mechanism of the toxic effects of a substance. [NIH] Pharmacologic: Pertaining to pharmacology or to the properties and reactions of drugs. [EU] Pharyngitis: Inflammation of the throat. [NIH] Pharynx: The hollow tube about 5 inches long that starts behind the nose and ends at the top of the trachea (windpipe) and esophagus (the tube that goes to the stomach). [NIH] 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] Phenyl: Ingredient used in cold and flu remedies. [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] Phorbol Esters: Tumor-promoting compounds obtained from croton oil (Croton tiglium). Some of these are used in cell biological experiments as activators of protein kinase C. [NIH] Phosphates: Inorganic salts of phosphoric acid. [NIH] Phosphodiesterase: Effector enzyme that regulates the levels of a second messenger, the cyclic GMP. [NIH] Phospholipases: A class of enzymes that catalyze the hydrolysis of phosphoglycerides or glycerophosphatidates. EC 3.1.-. [NIH] Phospholipids: Lipids containing one or more phosphate groups, particularly those derived from either glycerol (phosphoglycerides; glycerophospholipids) or sphingosine (sphingolipids). They are polar lipids that are of great importance for the structure and function of cell membranes and are the most abundant of membrane lipids, although not stored in large amounts in the system. [NIH] 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] Phosphorylated: Attached to a phosphate group. [NIH] Phosphorylating: Attached to a phosphate group. [NIH]
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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] Phosphotyrosine: An amino acid that occurs in endogenous proteins. Tyrosine phosphorylation and dephosphorylation plays a role in cellular signal transduction and possibly in cell growth control and carcinogenesis. [NIH] Photophobia: Abnormal sensitivity to light. This may occur as a manifestation of eye diseases; migraine; subarachnoid hemorrhage; meningitis; and other disorders. Photophobia may also occur in association with depression and other mental disorders. [NIH] Photoreceptor: Receptor capable of being activated by light stimuli, as a rod or cone cell of the eye. [NIH] Photosensitization: The development of abnormally heightened reactivity of the skin to sunlight. [EU] Phylogeny: The relationships of groups of organisms as reflected by their evolutionary history. [NIH] Physiologic: Having to do with the functions of the body. When used in the phrase "physiologic age," it refers to an age assigned by general health, as opposed to calendar age. [NIH]
Physiology: The science that deals with the life processes and functions of organismus, their cells, tissues, and organs. [NIH] Pigment: A substance that gives color to tissue. Pigments are responsible for the color of skin, eyes, and hair. [NIH] Pigmentation: Coloration or discoloration of a part by a pigment. [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] Plague: An acute infectious disease caused by Yersinia pestis that affects humans, wild rodents, and their ectoparasites. This condition persists due to its firm entrenchment in sylvatic rodent-flea ecosystems throughout the world. Bubonic plague is the most common form. [NIH] Plant Oils: Oils derived from plants or plant products. [NIH] Plants: Multicellular, eukaryotic life forms of the kingdom Plantae. They are characterized by a mainly photosynthetic mode of nutrition; essentially unlimited growth at localized regions of cell divisions (meristems); cellulose within cells providing rigidity; the absence of organs of locomotion; absense of nervous and sensory systems; and an alteration of haploid and diploid generations. [NIH] Plaque: A clear zone in a bacterial culture grown on an agar plate caused by localized destruction of bacterial cells by a bacteriophage. The concentration of infective virus in a fluid can be estimated by applying the fluid to a culture and counting the number of. [NIH] Plasma: The clear, yellowish, fluid part of the blood that carries the blood cells. The proteins that form blood clots are in plasma. [NIH] Plasma cells: A type of white blood cell that produces antibodies. [NIH] Plasma protein: One of the hundreds of different proteins present in blood plasma, including carrier proteins ( such albumin, transferrin, and haptoglobin), fibrinogen and other coagulation factors, complement components, immunoglobulins, enzyme inhibitors,
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precursors of substances such as angiotension and bradykinin, and many other types of proteins. [EU] Plasmid: An autonomously replicating, extra-chromosomal DNA molecule found in many bacteria. Plasmids are widely used as carriers of cloned genes. [NIH] Plasticity: In an individual or a population, the capacity for adaptation: a) through gene changes (genetic plasticity) or b) through internal physiological modifications in response to changes of environment (physiological plasticity). [NIH] Platelet Activation: A series of progressive, overlapping events triggered by exposure of the platelets to subendothelial tissue. These events include shape change, adhesiveness, aggregation, and release reactions. When carried through to completion, these events lead to the formation of a stable hemostatic plug. [NIH] Platelet Aggregation: The attachment of platelets to one another. This clumping together can be induced by a number of agents (e.g., thrombin, collagen) and is part of the mechanism leading to the formation of a thrombus. [NIH] Platelets: A type of blood cell that helps prevent bleeding by causing blood clots to form. Also called thrombocytes. [NIH] Platinum: Platinum. A heavy, soft, whitish metal, resembling tin, atomic number 78, atomic weight 195.09, symbol Pt. (From Dorland, 28th ed) It is used in manufacturing equipment for laboratory and industrial use. It occurs as a black powder (platinum black) and as a spongy substance (spongy platinum) and may have been known in Pliny's time as "alutiae". [NIH]
Pleura: The thin serous membrane enveloping the lungs and lining the thoracic cavity. [NIH] Pleural: A circumscribed area of hyaline whorled fibrous tissue which appears on the surface of the parietal pleura, on the fibrous part of the diaphragm or on the pleura in the interlobar fissures. [NIH] Pleural cavity: A space enclosed by the pleura (thin tissue covering the lungs and lining the interior wall of the chest cavity). It is bound by thin membranes. [NIH] Pleural Effusion: Presence of fluid in the pleural cavity resulting from excessive transudation or exudation from the pleural surfaces. It is a sign of disease and not a diagnosis in itself. [NIH] Pleurodesis: A surgical procedure that causes the membranes around the lung to stick together, and prevents the buildup of fluid in the space between the membranes. [NIH] Pneumonia: Inflammation of the lungs. [NIH] Pneumothorax: Accumulation of air or gas in the space between the lung and chest wall, resulting in partial or complete collapse of the lung. [NIH] Point Mutation: A mutation caused by the substitution of one nucleotide for another. This results in the DNA molecule having a change in a single base pair. [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] Polyarthritis: An inflammation of several joints together. [EU] Polycystic: An inherited disorder characterized by many grape-like clusters of fluid-filled cysts that make both kidneys larger over time. These cysts take over and destroy working
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kidney tissue. PKD may cause chronic renal failure and end-stage renal disease. [NIH] Polyethylene: A vinyl polymer made from ethylene. It can be branched or linear. Branched or low-density polyethylene is tough and pliable but not to the same degree as linear polyethylene. Linear or high-density polyethylene has a greater hardness and tensile strength. Polyethylene is used in a variety of products, including implants and prostheses. [NIH]
Polymerase: An enzyme which catalyses the synthesis of DNA using a single DNA strand as a template. The polymerase copies the template in the 5'-3'direction provided that sufficient quantities of free nucleotides, dATP and dTTP are present. [NIH] Polymerase Chain Reaction: In vitro method for producing large amounts of specific DNA or RNA fragments of defined length and sequence from small amounts of short oligonucleotide flanking sequences (primers). The essential steps include thermal denaturation of the double-stranded target molecules, annealing of the primers to their complementary sequences, and extension of the annealed primers by enzymatic synthesis with DNA polymerase. The reaction is efficient, specific, and extremely sensitive. Uses for the reaction include disease diagnosis, detection of difficult-to-isolate pathogens, mutation analysis, genetic testing, DNA sequencing, and analyzing evolutionary relationships. [NIH] Polymorphic: Occurring in several or many forms; appearing in different forms at different stages of development. [EU] Polypeptide: A peptide which on hydrolysis yields more than two amino acids; called tripeptides, tetrapeptides, etc. according to the number of amino acids contained. [EU] Polyposis: The development of numerous polyps (growths that protrude from a mucous membrane). [NIH] Polyproteins: Proteins which are synthesized as a single polymer and then cleaved into several distinct proteins. [NIH] Polysaccharide: A type of carbohydrate. It contains sugar molecules that are linked together chemically. [NIH] Population Dynamics: The pattern of any process, or the interrelationship of phenomena, which affects growth or change within a population. [NIH] Porphyria: A group of disorders characterized by the excessive production of porphyrins or their precursors that arises from abnormalities in the regulation of the porphyrin-heme pathway. The porphyrias are usually divided into three broad groups, erythropoietic, hepatic, and erythrohepatic, according to the major sites of abnormal porphyrin synthesis. [NIH]
Porphyrins: A group of compounds containing the porphin structure, four pyrrole rings connected by methine bridges in a cyclic configuration to which a variety of side chains are attached. The nature of the side chain is indicated by a prefix, as uroporphyrin, hematoporphyrin, etc. The porphyrins, in combination with iron, form the heme component in biologically significant compounds such as hemoglobin and myoglobin. [NIH] Posterior: Situated in back of, or in the back part of, or affecting the back or dorsal surface of the body. In lower animals, it refers to the caudal end of the body. [EU] Postmenopausal: Refers to the time after menopause. Menopause is the time in a woman's life when menstrual periods stop permanently; also called "change of life." [NIH] Postnatal: Occurring after birth, with reference to the newborn. [EU] Postoperative: After surgery. [NIH] Postoperative Period: The period following a surgical operation. [NIH] Postsynaptic: Nerve potential generated by an inhibitory hyperpolarizing stimulation. [NIH]
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Post-translational: The cleavage of signal sequence that directs the passage of the protein through a cell or organelle membrane. [NIH] Potassium: An element that is in the alkali group of metals. It has an atomic symbol K, atomic number 19, and atomic weight 39.10. It is the chief cation in the intracellular fluid of muscle and other cells. Potassium ion is a strong electrolyte and it plays a significant role in the regulation of fluid volume and maintenance of the water-electrolyte balance. [NIH] Potentiate: A degree of synergism which causes the exposure of the organism to a harmful substance to worsen a disease already contracted. [NIH] Potentiation: An overall effect of two drugs taken together which is greater than the sum of the effects of each drug taken alone. [NIH] Practice Guidelines: Directions or principles presenting current or future rules of policy for the health care practitioner to assist him in patient care decisions regarding diagnosis, therapy, or related clinical circumstances. The guidelines may be developed by government agencies at any level, institutions, professional societies, governing boards, or by the convening of expert panels. The guidelines form a basis for the evaluation of all aspects of health care and delivery. [NIH] Precancerous: A term used to describe a condition that may (or is likely to) become cancer. Also called premalignant. [NIH] Precipitating Factors: Factors associated with the definitive onset of a disease, illness, accident, behavioral response, or course of action. Usually one factor is more important or more obviously recognizable than others, if several are involved, and one may often be regarded as "necessary". Examples include exposure to specific disease; amount or level of an infectious organism, drug, or noxious agent, etc. [NIH] Preclinical: Before a disease becomes clinically recognizable. [EU] Precursor: Something that precedes. In biological processes, a substance from which another, usually more active or mature substance is formed. In clinical medicine, a sign or symptom that heralds another. [EU] Predisposition: A latent susceptibility to disease which may be activated under certain conditions, as by stress. [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] Prenatal: Existing or occurring before birth, with reference to the fetus. [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] Prickle: Several layers of the epidermis where the individual cells are connected by cell bridges. [NIH] Prion: Small proteinaceous infectious particles that resist inactivation by procedures modifying nucleic acids and contain an abnormal isoform of a cellular protein which is a major and necessary component. [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]
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Procaine: A local anesthetic of the ester type that has a slow onset and a short duration of action. It is mainly used for infiltration anesthesia, peripheral nerve block, and spinal block. (From Martindale, The Extra Pharmacopoeia, 30th ed, p1016). [NIH] Procollagen: A biosynthetic precursor of collagen containing additional amino acid sequences at the amino-terminal ends of the three polypeptide chains. Protocollagen, a precursor of procollagen consists of procollagen peptide chains in which proline and lysine have not yet been hydroxylated. [NIH] Proctocolitis: Inflammation of the rectum and colon. [NIH] Progeny: The offspring produced in any generation. [NIH] Progesterone: Pregn-4-ene-3,20-dione. The principal progestational hormone of the body, secreted by the corpus luteum, adrenal cortex, and placenta. Its chief function is to prepare the uterus for the reception and development of the fertilized ovum. It acts as an antiovulatory agent when administered on days 5-25 of the menstrual cycle. [NIH] Progression: Increase in the size of a tumor or spread of cancer in the body. [NIH] Progressive: Advancing; going forward; going from bad to worse; increasing in scope or severity. [EU] Projection: A defense mechanism, operating unconsciously, whereby that which is emotionally unacceptable in the self is rejected and attributed (projected) to others. [NIH] Prolactin: Pituitary lactogenic hormone. A polypeptide hormone with a molecular weight of about 23,000. It is essential in the induction of lactation in mammals at parturition and is synergistic with estrogen. The hormone also brings about the release of progesterone from lutein cells, which renders the uterine mucosa suited for the embedding of the ovum should fertilization occur. [NIH] Proline: A non-essential amino acid that is synthesized from glutamic acid. It is an essential component of collagen and is important for proper functioning of joints and tendons. [NIH] Promoter: A chemical substance that increases the activity of a carcinogenic process. [NIH] Promotor: In an operon, a nucleotide sequence located at the operator end which contains all the signals for the correct initiation of genetic transcription by the RNA polymerase holoenzyme and determines the maximal rate of RNA synthesis. [NIH] Prophase: The first phase of cell division, in which the chromosomes become visible, the nucleus starts to lose its identity, the spindle appears, and the centrioles migrate toward opposite poles. [NIH] Prophylaxis: An attempt to prevent disease. [NIH] Proportional: Being in proportion : corresponding in size, degree, or intensity, having the same or a constant ratio; of, relating to, or used in determining proportions. [EU] Propranolol: A widely used non-cardioselective beta-adrenergic antagonist. Propranolol is used in the treatment or prevention of many disorders including acute myocardial infarction, arrhythmias, angina pectoris, hypertension, hypertensive emergencies, hyperthyroidism, migraine, pheochromocytoma, menopause, and anxiety. [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]
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Prostaglandins: A group of compounds derived from unsaturated 20-carbon fatty acids, primarily arachidonic acid, via the cyclooxygenase pathway. They are extremely potent mediators of a diverse group of physiological processes. [NIH] 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] Prostaglandins F: (9 alpha,11 alpha,13E,15S)-9,11,15-Trihydroxyprost-13-en-1-oic acid (PGF(1 alpha)); (5Z,9 alpha,11,alpha,13E,15S)-9,11,15-trihydroxyprosta-5,13-dien-1-oic acid (PGF(2 alpha)); (5Z,9 alpha,11 alpha,13E,15S,17Z)-9,11,15-trihydroxyprosta-5,13,17-trien-1oic acid (PGF(3 alpha)). A family of prostaglandins that includes three of the six naturally occurring prostaglandins. All naturally occurring PGF have an alpha configuration at the 9carbon position. They stimulate uterine and bronchial smooth muscle and are often used as oxytocics. [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] Prostatitis: Inflammation of the prostate. [EU] Protease: Proteinase (= any enzyme that catalyses the splitting of interior peptide bonds in a protein). [EU] Protective Agents: Synthetic or natural substances which are given to prevent a disease or disorder or are used in the process of treating a disease or injury due to a poisonous agent. [NIH]
Protein Binding: The process in which substances, either endogenous or exogenous, bind to proteins, peptides, enzymes, protein precursors, or allied compounds. Specific proteinbinding measures are often used as assays in diagnostic assessments. [NIH] Protein C: A vitamin-K dependent zymogen present in the blood, which, upon activation by thrombin and thrombomodulin exerts anticoagulant properties by inactivating factors Va and VIIIa at the rate-limiting steps of thrombin formation. [NIH] Protein Conformation: The characteristic 3-dimensional shape of a protein, including the secondary, supersecondary (motifs), tertiary (domains) and quaternary structure of the peptide chain. Quaternary protein structure describes the conformation assumed by multimeric proteins (aggregates of more than one polypeptide chain). [NIH] Protein Folding: A rapid biochemical reaction involved in the formation of proteins. It begins even before a protein has been completely synthesized and proceeds through discrete intermediates (primary, secondary, and tertiary structures) before the final structure (quaternary structure) is developed. [NIH] Protein Kinases: A family of enzymes that catalyze the conversion of ATP and a protein to ADP and a phosphoprotein. EC 2.7.1.37. [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] 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
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working properly. [NIH] Proteoglycan: A molecule that contains both protein and glycosaminoglycans, which are a type of polysaccharide. Proteoglycans are found in cartilage and other connective tissues. [NIH]
Proteolytic: 1. Pertaining to, characterized by, or promoting proteolysis. 2. An enzyme that promotes proteolysis (= the splitting of proteins by hydrolysis of the peptide bonds with formation of smaller polypeptides). [EU] Protocol: The detailed plan for a clinical trial that states the trial's rationale, purpose, drug or vaccine dosages, length of study, routes of administration, who may participate, and other aspects of trial design. [NIH] Proton Pump: Integral membrane proteins that transport protons across a membrane against a concentration gradient. This transport is driven by hydrolysis of ATP by H(+)transporting ATP synthase. [NIH] Protons: Stable elementary particles having the smallest known positive charge, found in the nuclei of all elements. The proton mass is less than that of a neutron. A proton is the nucleus of the light hydrogen atom, i.e., the hydrogen ion. [NIH] Proto-Oncogenes: Normal cellular genes homologous to viral oncogenes. The products of proto-oncogenes are important regulators of biological processes and appear to be involved in the events that serve to maintain the ordered procession through the cell cycle. Protooncogenes have names of the form c-onc. [NIH] Protozoa: A subkingdom consisting of unicellular organisms that are the simplest in the animal kingdom. Most are free living. They range in size from submicroscopic to macroscopic. Protozoa are divided into seven phyla: Sarcomastigophora, Labyrinthomorpha, Apicomplexa, Microspora, Ascetospora, Myxozoa, and Ciliophora. [NIH] Protozoan: 1. Any individual of the protozoa; protozoon. 2. Of or pertaining to the protozoa; protozoal. [EU] Provirus: Virus that is integrated into the chromosome of a host cell and is transmitted in that form from one host cell generation to another without leading to the lysis of the host cells. [NIH] Proximal: Nearest; closer to any point of reference; opposed to distal. [EU] Pruritic: Pertaining to or characterized by pruritus. [EU] Psittacosis: A lung disease caused by a Chlamydia bacterium; occurs in domestic fowls, ducks, pigeons, turkeys and many wild birds and is contracted by man by contact with these birds; the human symptoms are headache, nausea, epistaxis and fever and usually with added symptoms. [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] Psychic: Pertaining to the psyche or to the mind; mental. [EU] Public Health: Branch of medicine concerned with the prevention and control of disease and disability, and the promotion of physical and mental health of the population on the international, national, state, or municipal level. [NIH]
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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 Embolism: Embolism in the pulmonary artery or one of its branches. [NIH] Pulmonary hypertension: Abnormally high blood pressure in the arteries of the lungs. [NIH] Pulse: The rhythmical expansion and contraction of an artery produced by waves of pressure caused by the ejection of blood from the left ventricle of the heart as it contracts. [NIH]
Pupil: The aperture in the iris through which light passes. [NIH] Purines: A series of heterocyclic compounds that are variously substituted in nature and are known also as purine bases. They include adenine and guanine, constituents of nucleic acids, as well as many alkaloids such as caffeine and theophylline. Uric acid is the metabolic end product of purine metabolism. [NIH] Purulent: Consisting of or containing pus; associated with the formation of or caused by pus. [EU] Pustular: Pertaining to or of the nature of a pustule; consisting of pustules (= a visible collection of pus within or beneath the epidermis). [EU] Pyogenic: Producing pus; pyopoietic (= liquid inflammation product made up of cells and a thin fluid called liquor puris). [EU] Pyrimidines: A family of 6-membered heterocyclic compounds occurring in nature in a wide variety of forms. They include several nucleic acid constituents (cytosine, thymine, and uracil) and form the basic structure of the barbiturates. [NIH] Quaternary: 1. Fourth in order. 2. Containing four elements or groups. [EU] Quercetin: Aglucon of quercetrin, rutin, and other glycosides. It is widely distributed in the plant kingdom, especially in rinds and barks, clover blossoms, and ragweed pollen. [NIH] Quinine: An alkaloid derived from the bark of the cinchona tree. It is used as an antimalarial drug, and is the active ingredient in extracts of the cinchona that have been used for that purpose since before 1633. Quinine is also a mild antipyretic and analgesic and has been used in common cold preparations for that purpose. It was used commonly and as a bitter and flavoring agent, and is still useful for the treatment of babesiosis. Quinine is also useful in some muscular disorders, especially nocturnal leg cramps and myotonia congenita, because of its direct effects on muscle membrane and sodium channels. The mechanisms of its antimalarial effects are not well understood. [NIH] Quinolinic: It is produced by immune cells and slowly infiltrates the brain tissues after an injury. [NIH] Quinolinic Acid: 2,3-Pyridinedicarboxylic acid. A metabolite of tryptophan with a possible role in neurodegenerative disorders. Elevated CSF levels of quinolinic acid are significantly correlated with the severity of neuropsychological deficits in patients who have AIDS. [NIH] Quinolones: Quinolines which are substituted in any position by one or more oxo groups. These compounds can have any degree of hydrogenation, any substituents, and fused ring
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systems. [NIH] Race: A population within a species which exhibits general similarities within itself, but is both discontinuous and distinct from other populations of that species, though not sufficiently so as to achieve the status of a taxon. [NIH] Radiation: Emission or propagation of electromagnetic energy (waves/rays), or the waves/rays themselves; a stream of electromagnetic particles (electrons, neutrons, protons, alpha particles) or a mixture of these. The most common source is the sun. [NIH] Radiation therapy: The use of high-energy radiation from x-rays, gamma rays, neutrons, and other sources to kill cancer cells and shrink tumors. Radiation may come from a machine outside the body (external-beam radiation therapy), or it may come from radioactive material placed in the body in the area near cancer cells (internal radiation therapy, implant radiation, or brachytherapy). Systemic radiation therapy uses a radioactive substance, such as a radiolabeled monoclonal antibody, that circulates throughout the body. Also called radiotherapy. [NIH] Radioactive: Giving off radiation. [NIH] Radioimmunotherapy: Radiotherapy where cytotoxic radionuclides are linked to antibodies in order to deliver toxins directly to tumor targets. Therapy with targeted radiation rather than antibody-targeted toxins (immunotoxins) has the advantage that adjacent tumor cells, which lack the appropriate antigenic determinants, can be destroyed by radiation cross-fire. Radioimmunotherapy is sometimes called targeted radiotherapy, but this latter term can also refer to radionuclides linked to non-immune molecules (radiotherapy). [NIH] Radioisotope: An unstable element that releases radiation as it breaks down. Radioisotopes can be used in imaging tests or as a treatment for cancer. [NIH] Radioisotope Renography: Graphic tracing over a time period of radioactivity measured externally over the kidneys following intravenous injection of a radionuclide which is taken up and excreted by the kidneys. [NIH] Radiolabeled: Any compound that has been joined with a radioactive substance. [NIH] Radiological: Pertaining to radiodiagnostic and radiotherapeutic procedures, and interventional radiology or other planning and guiding medical radiology. [NIH] Radiology: A specialty concerned with the use of x-ray and other forms of radiant energy in the diagnosis and treatment of disease. [NIH] Radionuclide Angiography: The measurement of visualization by radiation of any organ after a radionuclide has been injected into its blood supply. It is used to diagnose heart, liver, lung, and other diseases and to measure the function of those organs, except renography, for which radioisotope renography is available. [NIH] Radionuclide Imaging: Process whereby a radionuclide is injected or measured (through tissue) from an external source, and a display is obtained from any one of several rectilinear scanner or gamma camera systems. The image obtained from a moving detector is called a scan, while the image obtained from a stationary camera device is called a scintiphotograph. [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] Radius: The lateral bone of the forearm. [NIH] Raloxifene: A second generation selective estrogen receptor modulator (SERM) used to
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prevent osteoporosis in postmenopausal women. It has estrogen agonist effects on bone and cholesterol metabolism but behaves as a complete estrogen antagonist on mammary gland and uterine tissue. [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] Ranitidine: A non-imidazole blocker of those histamine receptors that mediate gastric secretion (H2 receptors). It is used to treat gastrointestinal ulcers. [NIH] Ranitidine Bismuth Citrate: Drug used to eradicate Helicobacter pylori. [NIH] Reactive Oxygen Species: Reactive intermediate oxygen species including both radicals and non-radicals. These substances are constantly formed in the human body and have been shown to kill bacteria and inactivate proteins, and have been implicated in a number of diseases. Scientific data exist that link the reactive oxygen species produced by inflammatory phagocytes to cancer development. [NIH] 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, Antigen: Molecules on the surface of B- and T-lymphocytes that recognize and combine with specific antigens. [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] Reconstitution: 1. A type of regeneration in which a new organ forms by the rearrangement of tissues rather than from new formation at an injured surface. 2. The restoration to original form of a substance previously altered for preservation and storage, as the restoration to a liquid state of blood serum or plasma that has been dried and stored. [EU] 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] Red blood cells: RBCs. Cells that carry oxygen to all parts of the body. Also called erythrocytes. [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] Refraction: A test to determine the best eyeglasses or contact lenses to correct a refractive error (myopia, hyperopia, or astigmatism). [NIH]
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Regeneration: The natural renewal of a structure, as of a lost tissue or part. [EU] Regimen: A treatment plan that specifies the dosage, the schedule, and the duration of treatment. [NIH] Reinfection: A second infection by the same pathogenic agent, or a second infection of an organ such as the kidney by a different pathogenic agent. [EU] Relapse: The return of signs and symptoms of cancer after a period of improvement. [NIH] 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 cysts: Abnormal fluid-filled sacs in the kidney that range in size from microscopic to much larger. Many simple cysts are harmless, while other types can seriously damage the kidneys. [NIH] Renal failure: Progressive renal insufficiency and uremia, due to irreversible and progressive renal glomerular tubular or interstitial disease. [NIH] Renin: An enzyme which is secreted by the kidney and is formed from prorenin in plasma and kidney. The enzyme cleaves the Leu-Leu bond in angiotensinogen to generate angiotensin I. EC 3.4.23.15. (Formerly EC 3.4.99.19). [NIH] Renin-Angiotensin System: A system consisting of renin, angiotensin-converting enzyme, and angiotensin II. Renin, an enzyme produced in the kidney, acts on angiotensinogen, an alpha-2 globulin produced by the liver, forming angiotensin I. The converting enzyme contained in the lung acts on angiotensin I in the plasma converting it to angiotensin II, the most powerful directly pressor substance known. It causes contraction of the arteriolar smooth muscle and has other indirect actions mediated through the adrenal cortex. [NIH] Reperfusion: Restoration of blood supply to tissue which is ischemic due to decrease in normal blood supply. The decrease may result from any source including atherosclerotic obstruction, narrowing of the artery, or surgical clamping. It is primarily a procedure for treating infarction or other ischemia, by enabling viable ischemic tissue to recover, thus limiting further necrosis. However, it is thought that reperfusion can itself further damage the ischemic tissue, causing reperfusion injury. [NIH] Reperfusion Injury: Functional, metabolic, or structural changes, including necrosis, in ischemic tissues thought to result from reperfusion to ischemic areas of the tissue. The most common instance is myocardial reperfusion injury. [NIH] Replication Origin: The point or region (origin) at which DNA replication begins in a bacterium or virus. Plasmids used in rec DNA research always contain an ori region, which gives very efficient initiation of replication. [NIH] Replicon: In order to be replicated, DNA molecules must contain an origin of duplication and in bacteria and viruses there is usually only one per genome. Such molecules are called replicons. [NIH] Repressor: Any of the specific allosteric protein molecules, products of regulator genes, which bind to the operator of operons and prevent RNA polymerase from proceeding into the operon to transcribe messenger RNA. [NIH] Repressor Proteins: Proteins which are normally bound to the operator locus of an operon, thereby preventing transcription of the structural genes. In enzyme induction, the substrate of the inducible enzyme binds to the repressor protein, causing its release from the operator and freeing the structural genes for transcription. In enzyme repression, the end product of the enzyme sequence binds to the free repressor protein, the resulting complex then binds to
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the operator and prevents transcription of the structural genes. [NIH] Resection: Removal of tissue or part or all of an organ by surgery. [NIH] Reserpine: An alkaloid found in the roots of Rauwolfia serpentina and R. vomitoria. Reserpine inhibits the uptake of norepinephrine into storage vesicles resulting in depletion of catecholamines and serotonin from central and peripheral axon terminals. It has been used as an antihypertensive and an antipsychotic as well as a research tool, but its adverse effects limit its clinical use. [NIH] Resorption: The loss of substance through physiologic or pathologic means, such as loss of dentin and cementum of a tooth, or of the alveolar process of the mandible or maxilla. [EU] Respiration: The act of breathing with the lungs, consisting of inspiration, or the taking into the lungs of the ambient air, and of expiration, or the expelling of the modified air which contains more carbon dioxide than the air taken in (Blakiston's Gould Medical Dictionary, 4th ed.). This does not include tissue respiration (= oxygen consumption) or cell respiration (= cell respiration). [NIH] Respiratory distress syndrome: A lung disease that occurs primarily in premature infants; the newborn must struggle for each breath and blueing of its skin reflects the baby's inability to get enough oxygen. [NIH] Response Elements: Nucleotide sequences, usually upstream, which are recognized by specific regulatory transcription factors, thereby causing gene response to various regulatory agents. These elements may be found in both promotor and enhancer regions. [NIH]
Restitution: The restoration to a normal state. [NIH] Restoration: Broad term applied to any inlay, crown, bridge or complete denture which restores or replaces loss of teeth or oral tissues. [NIH] Retina: The ten-layered nervous tissue membrane of the eye. It is continuous with the optic nerve and receives images of external objects and transmits visual impulses to the brain. Its outer surface is in contact with the choroid and the inner surface with the vitreous body. The outer-most layer is pigmented, whereas the inner nine layers are transparent. [NIH] Retinae: A congenital notch or cleft of the retina, usually located inferiorly. [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 pigment epithelium: The pigment cell layer that nourishes the retinal cells; located just outside the retina and attached to the choroid. [NIH] Retinitis: Inflammation of the retina. It is rarely limited to the retina, but is commonly associated with diseases of the choroid (chorioretinitis) and of the optic nerve (neuroretinitis). The disease may be confined to one eye, but since it is generally dependent on a constitutional factor, it is almost always bilateral. It may be acute in course, but as a rule it lasts many weeks or even several months. [NIH] Retinoblastoma: An eye cancer that most often occurs in children younger than 5 years. It occurs in hereditary and nonhereditary (sporadic) forms. [NIH] Retinoblastoma Protein: Product of the retinoblastoma tumor suppressor gene. It is a
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nuclear phosphoprotein hypothesized to normally act as an inhibitor of cell proliferation. Rb protein is absent in retinoblastoma cell lines. It also has been shown to form complexes with the adenovirus E1A protein, the SV40 T antigen, and the human papilloma virus E7 protein. [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] Retinopathy: 1. Retinitis (= inflammation of the retina). 2. Retinosis (= degenerative, noninflammatory condition of the retina). [EU] Retrograde: 1. Moving backward or against the usual direction of flow. 2. Degenerating, deteriorating, or catabolic. [EU] Retroviral vector: RNA from a virus that is used to insert genetic material into cells. [NIH] Retrovirus: A member of a group of RNA viruses, the RNA of which is copied during viral replication into DNA by reverse transcriptase. The viral DNA is then able to be integrated into the host chromosomal DNA. [NIH] Reversion: A return to the original condition, e. g. the reappearance of the normal or wild type in previously mutated cells, tissues, or organisms. [NIH] Rheumatism: A group of disorders marked by inflammation or pain in the connective tissue structures of the body. These structures include bone, cartilage, and fat. [NIH] Rheumatoid: Resembling rheumatism. [EU] Rheumatoid arthritis: A form of arthritis, the cause of which is unknown, although infection, hypersensitivity, hormone imbalance and psychologic stress have been suggested as possible causes. [NIH] Rhinophyma: A manifestation of severe Acne rosacea resulting in significant enlargement of the nose and occurring primarily in men. It is caused by hypertrophy of the sebaceous glands and surrounding connective tissue. The nose is reddened and marked with numerous telangiectasias. [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] Ribonuclease: RNA-digesting enzyme. [NIH] Ribonucleoside Diphosphate Reductase: An enzyme of the oxidoreductase class that catalyzes the formation of 2'-deoxyribonucleotides from the corresponding ribonucleotides using NADPH as the ultimate electron donor. The deoxyribonucleoside diphosphates are used in DNA synthesis. (From Dorland, 27th ed) EC 1.17.4.1. [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] Rickets: A condition caused by deficiency of vitamin D, especially in infancy and childhood, with disturbance of normal ossification. The disease is marked by bending and distortion of the bones under muscular action, by the formation of nodular enlargements on the ends and sides of the bones, by delayed closure of the fontanelles, pain in the muscles, and sweating of the head. Vitamin D and sunlight together with an adequate diet are curative, provided
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that the parathyroid glands are functioning properly. [EU] Rickettsia: A genus of gram-negative, aerobic, rod-shaped bacteria often surrounded by a protein microcapsular layer and slime layer. The natural cycle of its organisms generally involves a vertebrate and an invertebrate host. Species of the genus are the etiological agents of human diseases, such as typhus. [NIH] Rickettsiae: One of a group of obligate intracellular parasitic microorganisms, once regarded as intermediate in their properties between bacteria and viruses but now classified as bacteria in the order Rickettsiales, which includes 17 genera and 3 families: Rickettsiace. [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] Rod: A reception for vision, located in the retina. [NIH] Rolitetracycline: A semisynthetic antibiotic prepared from tetracycline. It is usually administered as an injection. [NIH] Root Planing: A procedure for smoothing of the roughened root surface or cementum of a tooth after subgingival curettage or scaling, as part of periodontal therapy. [NIH] Roxithromycin: Semisynthetic derivative of erythromycin. It is concentrated by human phagocytes and is bioactive intracellularly. While the drug is active against a wide spectrum of pathogens, it is particularly effective in the treatment of respiratory and genital tract infections. [NIH] Rubella: An acute, usually benign, infectious disease caused by a togavirus and most often affecting children and nonimmune young adults, in which the virus enters the respiratory tract via droplet nuclei and spreads to the lymphatic system. It is characterized by a slight cold, sore throat, and fever, followed by enlargement of the postauricular, suboccipital, and cervical lymph nodes, and the appearances of a fine pink rash that begins on the head and spreads to become generalized. Called also German measles, roetln, röteln, and three-day measles, and rubeola in French and Spanish. [EU] Rutin: 3-((6-O-(6-Deoxy-alpha-L-mannopyranosyl)-beta-D-glucopyranosyl)oxy)-2-(3,4dihydroxyphenyl)-5,7-dihydroxy-4H-1-benzopyran-4-one. Found in many plants, including buckwheat, tobacco, forsythia, hydrangea, pansies, etc. It has been used therapeutically to decrease capillary fragility. [NIH] Saliva: The clear, viscous fluid secreted by the salivary glands and mucous glands of the mouth. It contains mucins, water, organic salts, and ptylin. [NIH] Salivary: The duct that convey saliva to the mouth. [NIH] Salivary glands: Glands in the mouth that produce saliva. [NIH] Salpingitis: 1. Inflammation of the uterine tube. 2. Inflammation of the auditory tube. [EU] 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] Sarcoid: A cutaneus lesion occurring as a manifestation of sarcoidosis. [NIH] Sarcoidosis: An idiopathic systemic inflammatory granulomatous disorder comprised of epithelioid and multinucleated giant cells with little necrosis. It usually invades the lungs
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with fibrosis and may also involve lymph nodes, skin, liver, spleen, eyes, phalangeal bones, and parotid glands. [NIH] Sarcolemma: The plasma membrane of a smooth, striated, or cardiac muscle fiber. [NIH] Sarcoma: A connective tissue neoplasm formed by proliferation of mesodermal cells; it is usually highly malignant. [NIH] Sarcoplasmic Reticulum: A network of tubules and sacs in the cytoplasm of skeletal muscles that assist with muscle contraction and relaxation by releasing and storing calcium ions. [NIH] Saturated fat: A type of fat found in greatest amounts in foods from animals, such as fatty cuts of meat, poultry with the skin, whole-milk dairy products, lard, and in some vegetable oils, including coconut, palm kernel, and palm oils. Saturated fat raises blood cholesterol more than anything else eaten. On a Step I Diet, no more than 8 to 10 percent of total calories should come from saturated fat, and in the Step II Diet, less than 7 percent of the day's total calories should come from saturated fat. [NIH] Sclera: The tough white outer coat of the eyeball, covering approximately the posterior fivesixths of its surface, and continuous anteriorly with the cornea and posteriorly with the external sheath of the optic nerve. [EU] Sclerosis: A pathological process consisting of hardening or fibrosis of an anatomical structure, often a vessel or a nerve. [NIH] Sclerotherapy: Treatment of varicose veins, hemorrhoids, gastric and esophageal varices, and peptic ulcer hemorrhage by injection or infusion of chemical agents which cause localized thrombosis and eventual fibrosis and obliteration of the vessels. [NIH] Screening: Checking for disease when there are no symptoms. [NIH] Sebaceous: Gland that secretes sebum. [NIH] Sebaceous gland: Gland that secretes sebum. [NIH] Sebum: The oily substance secreted by sebaceous glands. It is composed of keratin, fat, and cellular debris. [NIH] Secondary tumor: Cancer that has spread from the organ in which it first appeared to another organ. For example, breast cancer cells may spread (metastasize) to the lungs and cause the growth of a new tumor. When this happens, the disease is called metastatic breast cancer, and the tumor in the lungs is called a secondary tumor. Also called secondary cancer. [NIH] Secretion: 1. The process of elaborating a specific product as a result of the activity of a gland; this activity may range from separating a specific substance of the blood to the elaboration of a new chemical substance. 2. Any substance produced by secretion. [EU] Secretory: Secreting; relating to or influencing secretion or the secretions. [NIH] Segregation: The separation in meiotic cell division of homologous chromosome pairs and their contained allelomorphic gene pairs. [NIH] Selective estrogen receptor modulator: SERM. A drug that acts like estrogen on some tissues, but blocks the effect of estrogen on other tissues. Tamoxifen and raloxifene are SERMs. [NIH] Semen: The thick, yellowish-white, viscid fluid secretion of male reproductive organs discharged upon ejaculation. In addition to reproductive organ secretions, it contains spermatozoa and their nutrient plasma. [NIH] Seminiferous tubule: Tube used to transport sperm made in the testes. [NIH] Semisynthetic: Produced by chemical manipulation of naturally occurring substances. [EU]
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Senescence: The bodily and mental state associated with advancing age. [NIH] Senile: Relating or belonging to old age; characteristic of old age; resulting from infirmity of old age. [NIH] Sensor: A device designed to respond to physical stimuli such as temperature, light, magnetism or movement and transmit resulting impulses for interpretation, recording, movement, or operating control. [NIH] Sepsis: The presence of bacteria in the bloodstream. [NIH] Septic: Produced by or due to decomposition by microorganisms; putrefactive. [EU] Septicemia: Systemic disease associated with the presence and persistence of pathogenic microorganisms or their toxins in the blood. Called also blood poisoning. [EU] Sequence Analysis: A multistage process that includes the determination of a sequence (protein, carbohydrate, etc.), its fragmentation and analysis, and the interpretation of the resulting sequence information. [NIH] Sequence Homology: The degree of similarity between sequences. Studies of amino acid and nucleotide sequences provide useful information about the genetic relatedness of certain species. [NIH] Sequencing: The determination of the order of nucleotides in a DNA or RNA chain. [NIH] Serine: A non-essential amino acid occurring in natural form as the L-isomer. It is synthesized from glycine or threonine. It is involved in the biosynthesis of purines, pyrimidines, and other amino acids. [NIH] 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] Serous: Having to do with serum, the clear liquid part of blood. [NIH] Serum: The clear liquid part of the blood that remains after blood cells and clotting proteins have been removed. [NIH] Serum Albumin: A major plasma protein that serves in maintaining the plasma colloidal osmotic pressure and transporting large organic anions. [NIH] Sex Characteristics: Those characteristics that distinguish one sex from the other. The primary sex characteristics are the ovaries and testes and their related hormones. Secondary sex characteristics are those which are masculine or feminine but not directly related to reproduction. [NIH] Sexual Partners: Married or single individuals who share sexual relations. [NIH] Sexually Transmitted Diseases: Diseases due to or propagated by sexual contact. [NIH] Shame: An emotional attitude excited by realization of a shortcoming or impropriety. [NIH] Shedding: Release of infectious particles (e. g., bacteria, viruses) into the environment, for example by sneezing, by fecal excretion, or from an open lesion. [NIH] Shigellosis: Infection with the bacterium Shigella. Usually causes a high fever, acute diarrhea, and dehydration. [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.
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[NIH]
Short Bowel Syndrome: A malabsorption syndrome resulting from extensive operative resection of small bowel. [NIH] Shyness: Discomfort and partial inhibition of the usual forms of behavior when in the presence of others. [NIH] Sicca: Failure of lacrimal secretion, keratoconjunctivitis sicca, failure of secretion of the salivary glands and mucous glands of the upper respiratory tract and polyarthritis. [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 differentiation, and cell proliferation. Examples of signal transduction systems are the GABA-postsynaptic receptor-calcium ion channel system, the receptor-mediated T-cell activation pathway, and the receptor-mediated activation of phospholipases. Those coupled to membrane depolarization or intracellular release of calcium include the receptormediated activation of cytotoxic functions in granulocytes and the synaptic potentiation of protein kinase activation. Some signal transduction pathways may be part of larger signal transduction pathways; for example, protein kinase activation is part of the platelet activation signal pathway. [NIH] Signs and Symptoms: Clinical manifestations that can be either objective when observed by a physician, or subjective when perceived by the patient. [NIH] Single-agent: The use of a single drug or other therapy. [NIH] Sinusitis: An inflammatory process of the mucous membranes of the paranasal sinuses that occurs in three stages: acute, subacute, and chronic. Sinusitis results from any condition causing ostial obstruction or from pathophysiologic changes in the mucociliary transport mechanism. [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] Smallpox: A generalized virus infection with a vesicular rash. [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,
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27th ed) Physiologically the sodium ion plays a major role in blood pressure regulation, maintenance of fluid volume, and electrolyte balance. [NIH] Sodium Dodecyl Sulfate: An anionic surfactant, usually a mixture of sodium alkyl sulfates, mainly the lauryl; lowers surface tension of aqueous solutions; used as fat emulsifier, wetting agent, detergent in cosmetics, pharmaceuticals and toothpastes; also as research tool in protein biochemistry. [NIH] Sodium Fluoride: A source of inorganic fluoride which is used topically to prevent dental caries. [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] Soma: The body as distinct from the mind; all the body tissue except the germ cells; all the axial body. [NIH] Somatic: 1. Pertaining to or characteristic of the soma or body. 2. Pertaining to the body wall in contrast to the viscera. [EU] Somatic cells: All the body cells except the reproductive (germ) cells. [NIH] Soybean Oil: Oil from soybean or soybean plant. [NIH] 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] Species Specificity: Restriction of a characteristic or response to the members of one species; it usually refers to that property of the immune response which differentiates one species from another on the basis of antigen recognition, but the concept is not limited to immunology and is used loosely at levels higher than the species. [NIH] 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] Spectinomycin: An antibiotic produced by Streptomyces spectabilis. It is active against gram-negative bacteria and used for the treatment of gonorrhea. [NIH] Spectrin: A high molecular weight (220-250 kDa) water-soluble protein which can be extracted from erythrocyte ghosts in low ionic strength buffers. The protein contains no lipids or carbohydrates, is the predominant species of peripheral erythrocyte membrane proteins, and exists as a fibrous coating on the inner, cytoplasmic surface of the membrane. [NIH]
Spectrophotometry: The art or process of comparing photometrically the relative intensities of the light in different parts of the spectrum. [NIH] Spectrum: A charted band of wavelengths of electromagnetic vibrations obtained by refraction and diffraction. By extension, a measurable range of activity, such as the range of bacteria affected by an antibiotic (antibacterial s.) or the complete range of manifestations of a disease. [EU]
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Sperm: The fecundating fluid of the male. [NIH] Sphincter: A ringlike band of muscle fibres that constricts a passage or closes a natural orifice; called also musculus sphincter. [EU] 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 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] Spiramycin: A macrolide antibiotic produced by Streptomyces ambofaciens. The drug is effective against gram-positive aerobic pathogens, N. gonorrhoeae, and staphylococci. It is used to treat infections caused by bacteria and Toxoplasma gondii. [NIH] Spirochete: Lyme disease. [NIH] Spleen: An organ that is part of the lymphatic system. The spleen produces lymphocytes, filters the blood, stores blood cells, and destroys old blood cells. It is located on the left side of the abdomen near the stomach. [NIH] Spondylitis: Inflammation of the vertebrae. [EU] Sporadic: Neither endemic nor epidemic; occurring occasionally in a random or isolated manner. [EU] Spores: The reproductive elements of lower organisms, such as protozoa, fungi, and cryptogamic plants. [NIH] Sprue: A non febrile tropical disease of uncertain origin. [NIH] Sputum: The material expelled from the respiratory passages by coughing or clearing the throat. [NIH] Stabilization: The creation of a stable state. [EU] Staphylococcus: A genus of gram-positive, facultatively anaerobic, coccoid bacteria. Its organisms occur singly, in pairs, and in tetrads and characteristically divide in more than one plane to form irregular clusters. Natural populations of Staphylococcus are membranes of warm-blooded animals. Some species are opportunistic pathogens of humans and animals. [NIH] Staphylococcus aureus: Potentially pathogenic bacteria found in nasal membranes, skin, hair follicles, and perineum of warm-blooded animals. They may cause a wide range of infections and intoxications. [NIH] Steatosis: Fatty degeneration. [EU] Stem Cells: Relatively undifferentiated cells of the same lineage (family type) that retain the ability to divide and cycle throughout postnatal life to provide cells that can become specialized and take the place of those that die or are lost. [NIH] Stent: A device placed in a body structure (such as a blood vessel or the gastrointestinal tract) to provide support and keep the structure open. [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,
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bile acids, sterols (such as cholesterol), toad poisons, saponins, and some of the carcinogenic hydrocarbons. [EU] Stimulant: 1. Producing stimulation; especially producing stimulation by causing tension on muscle fibre through the nervous tissue. 2. An agent or remedy that produces stimulation. [EU]
Stimulus: That which can elicit or evoke action (response) in a muscle, nerve, gland or other excitable issue, or cause an augmenting action upon any function or metabolic process. [NIH] Stoma: A surgically created opening from an area inside the body to the outside. [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] Stomatitis: Inflammation of the oral mucosa, due to local or systemic factors which may involve the buccal and labial mucosa, palate, tongue, floor of the mouth, and the gingivae. [EU]
Stool: The waste matter discharged in a bowel movement; feces. [NIH] Strand: DNA normally exists in the bacterial nucleus in a helix, in which two strands are coiled together. [NIH] Streptococcal: Caused by infection due to any species of streptococcus. [NIH] Streptococci: A genus of spherical Gram-positive bacteria occurring in chains or pairs. They are widely distributed in nature, being important pathogens but often found as normal commensals in the mouth, skin, and intestine of humans and other animals. [NIH] Streptococcus: A genus of gram-positive, coccoid bacteria whose organisms occur in pairs or chains. No endospores are produced. Many species exist as commensals or parasites on man or animals with some being highly pathogenic. A few species are saprophytes and occur in the natural environment. [NIH] Streptomyces: A genus of bacteria that form a nonfragmented aerial mycelium. Many species have been identified with some being pathogenic. This genus is responsible for producing a majority of the antibiotics of practical value. [NIH] Streptomycin: O-2-Deoxy-2-(methylamino)-alpha-L-glucopyranosyl-(1-2)-O-5- deoxy-3-Cformyl-alpha-L-lyxofuranosyl-(1-4)-N,N'-bis(aminoiminomethyl)-D-streptamine. Antibiotic substance produced by the soil actinomycete Streptomyces griseus. It acts by inhibiting the initiation and elongation processes during protein synthesis. [NIH] Stress: Forcibly exerted influence; pressure. Any condition or situation that causes strain or tension. Stress may be either physical or psychologic, or both. [NIH] Striatum: A higher brain's domain thus called because of its stripes. [NIH] Stroke: Sudden loss of function of part of the brain because of loss of blood flow. Stroke may be caused by a clot (thrombosis) or rupture (hemorrhage) of a blood vessel to the brain. [NIH] Stroma: The middle, thickest layer of tissue in the cornea. [NIH] Stromal: Large, veil-like cell in the bone marrow. [NIH] Subacute: Somewhat acute; between acute and chronic. [EU] Subarachnoid: Situated or occurring between the arachnoid and the pia mater. [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]
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Submaxillary: Four to six lymph glands, located between the lower jaw and the submandibular salivary gland. [NIH] Subspecies: A category intermediate in rank between species and variety, based on a smaller number of correlated characters than are used to differentiate species and generally conditioned by geographical and/or ecological occurrence. [NIH] Substance P: An eleven-amino acid neurotransmitter that appears in both the central and peripheral nervous systems. It is involved in transmission of pain, causes rapid contractions of the gastrointestinal smooth muscle, and modulates inflammatory and immune responses. [NIH]
Substrate: A substance upon which an enzyme acts. [EU] Substrate Specificity: A characteristic feature of enzyme activity in relation to the kind of substrate on which the enzyme or catalytic molecule reacts. [NIH] Sucralfate: A basic aluminum complex of sulfated sucrose. It is advocated in the therapy of peptic, duodenal, and prepyloric ulcers, gastritis, reflux esophagitis, and other gastrointestinal irritations. It acts primarily at the ulcer site, where it has cytoprotective, pepsinostatic, antacid, and bile acid-binding properties. The drug is only slightly absorbed by the digestive mucosa, which explains the absence of systemic effects and toxicity. [NIH] Sulfates: Inorganic salts of sulfuric acid. [NIH] Sulfuric acid: A strong acid that, when concentrated is extemely corrosive to the skin and mucous membranes. It is used in making fertilizers, dyes, electroplating, and industrial explosives. [NIH] Sunburn: An injury to the skin causing erythema, tenderness, and sometimes blistering and resulting from excessive exposure to the sun. The reaction is produced by the ultraviolet radiation in sunlight. [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] Suppositories: A small cone-shaped medicament having cocoa butter or gelatin at its basis and usually intended for the treatment of local conditions in the rectum. [NIH] Suppression: A conscious exclusion of disapproved desire contrary with repression, in which the process of exclusion is not conscious. [NIH] Suppressive: Tending to suppress : effecting suppression; specifically : serving to suppress activity, function, symptoms. [EU] Surfactant: A fat-containing protein in the respiratory passages which reduces the surface tension of pulmonary fluids and contributes to the elastic properties of pulmonary tissue. [NIH]
Sympathomimetic: 1. Mimicking the effects of impulses conveyed by adrenergic postganglionic fibres of the sympathetic nervous system. 2. An agent that produces effects similar to those of impulses conveyed by adrenergic postganglionic fibres of the sympathetic nervous system. Called also adrenergic. [EU] Symphysis: A secondary cartilaginous joint. [NIH] Symptomatic: Having to do with symptoms, which are signs of a condition or disease. [NIH] Symptomatology: 1. That branch of medicine with treats of symptoms; the systematic discussion of symptoms. 2. The combined symptoms of a disease. [EU] Synapse: The region where the processes of two neurons come into close contiguity, and the
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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] Synergistic: Acting together; enhancing the effect of another force or agent. [EU] Synovial: Of pertaining to, or secreting synovia. [EU] Syphilis: A contagious venereal disease caused by the spirochete Treponema pallidum. [NIH]
Systemic: Affecting the entire body. [NIH] Systemic disease: Disease that affects the whole 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] Tacrolimus: A macrolide isolated from the culture broth of a strain of Streptomyces tsukubaensis that has strong immunosuppressive activity in vivo and prevents the activation of T-lymphocytes in response to antigenic or mitogenic stimulation in vitro. [NIH] Talc: A native magnesium silicate. [NIH] Talcum: A native magnesium silicate. [NIH] Talcum powder: A native magnesium silicate. [NIH] Tear Gases: Gases that irritate the eyes, throat, or skin. Severe lacrimation develops upon irritation of the eyes. [NIH] Teichoic Acids: Bacterial polysaccharides that are rich in phosphodiester linkages. They are the major components of the cell walls and membranes of many bacteria. [NIH] Telangiectasia: The permanent enlargement of blood vessels, causing redness in the skin or mucous membranes. [NIH] 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] Testicular: Pertaining to a testis. [EU] Testis: Either of the paired male reproductive glands that produce the male germ cells and the male hormones. [NIH] Tetracycline: An antibiotic originally produced by Streptomyces viridifaciens, but used mostly in synthetic form. It is an inhibitor of aminoacyl-tRNA binding during protein synthesis. [NIH] Tetracycline Resistance: Nonsusceptibility of a microbe (usually a bacterium) to the action of tetracycline, which binds to the 30S ribosomal subunit and prevents the normal binding
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of aminoacyl-tRNA. [NIH] Therapeutics: The branch of medicine which is concerned with the treatment of diseases, palliative or curative. [NIH] Thermal: Pertaining to or characterized by heat. [EU] Thigh: A leg; in anatomy, any elongated process or part of a structure more or less comparable to a leg. [NIH] Thoracic: Having to do with the chest. [NIH] Thoracostomy: Surgical creation of an opening (stoma) into the chest cavity for drainage; used in the treatment of pleural effusion, pneumothorax, hemothorax and empyema. [NIH] Threonine: An essential amino acid occurring naturally in the L-form, which is the active form. It is found in eggs, milk, gelatin, and other proteins. [NIH] Threshold: For a specified sensory modality (e. g. light, sound, vibration), the lowest level (absolute threshold) or smallest difference (difference threshold, difference limen) or intensity of the stimulus discernible in prescribed conditions of stimulation. [NIH] Thrombin: An enzyme formed from prothrombin that converts fibrinogen to fibrin. (Dorland, 27th ed) EC 3.4.21.5. [NIH] Thrombocytes: Blood cells that help prevent bleeding by causing blood clots to form. Also called 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] Thromboxanes: Physiologically active compounds found in many organs of the body. They are formed in vivo from the prostaglandin endoperoxides and cause platelet aggregation, contraction of arteries, and other biological effects. Thromboxanes are important mediators of the actions of polyunsaturated fatty acids transformed by cyclooxygenase. [NIH] Thrombus: An aggregation of blood factors, primarily platelets and fibrin with entrapment of cellular elements, frequently causing vascular obstruction at the point of its formation. Some authorities thus differentiate thrombus formation from simple coagulation or clot formation. [EU] Thrush: A disease due to infection with species of fungi of the genus Candida. [NIH] Thymidine: A chemical compound found in DNA. Also used as treatment for mucositis. [NIH]
Thymidine Kinase: An enzyme that catalyzes the conversion of ATP and thymidine to ADP and thymidine 5'-phosphate. Deoxyuridine can also act as an acceptor and dGTP as a donor. (From Enzyme Nomenclature, 1992) EC 2.7.1.21. [NIH] Thymus: An organ that is part of the lymphatic system, in which T lymphocytes grow and multiply. The thymus is in the chest behind the breastbone. [NIH] Thyroid: A gland located near the windpipe (trachea) that produces thyroid hormone, which helps regulate growth and metabolism. [NIH] 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] Thyroid Nodule: A small circumscribed mass of differentiated tissue associated with the thyroid gland. It can be pathogenic or non-pathogenic. The growth of nodules can lead to a condition of nodular goiter. Most nodules appear between the ages of 30 and 50 years and
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most are benign. [NIH] Thyroxine: An amino acid of the thyroid gland which exerts a stimulating effect on thyroid metabolism. [NIH] Tic: An involuntary compulsive, repetitive, stereotyped movement, resembling a purposeful movement because it is coordinated and involves muscles in their normal synergistic relationships; tics usually involve the face and shoulders. [EU] Tinea Pedis: Dermatological pruritic lesion in the feet, caused by Trichophyton rubrum, T. mentagrophytes, or Epidermophyton floccosum. [NIH] Tinidazole: A nitroimidazole antitrichomonal agent effective against Trichomonas vaginalis, Entamoeba histolytica, and Giardia lamblia infections. [NIH] Tissue: A group or layer of cells that are alike in type and work together to perform a specific function. [NIH] Tissue Culture: Maintaining or growing of tissue, organ primordia, or the whole or part of an organ in vitro so as to preserve its architecture and/or function (Dorland, 28th ed). Tissue culture includes both organ culture and cell culture. [NIH] Tissue Distribution: Accumulation of a drug or chemical substance in various organs (including those not relevant to its pharmacologic or therapeutic action). This distribution depends on the blood flow or perfusion rate of the organ, the ability of the drug to penetrate organ membranes, tissue specificity, protein binding. The distribution is usually expressed as tissue to plasma ratios. [NIH] Titre: The quantity of a substance required to produce a reaction with a given volume of another substance, or the amount of one substance required to correspond with a given amount of another substance. [EU] Tolerance: 1. The ability to endure unusually large doses of a drug or toxin. 2. Acquired drug tolerance; a decreasing response to repeated constant doses of a drug or the need for increasing doses to maintain a constant response. [EU] 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] Tone: 1. The normal degree of vigour and tension; in muscle, the resistance to passive elongation or stretch; tonus. 2. A particular quality of sound or of voice. 3. To make permanent, or to change, the colour of silver stain by chemical treatment, usually with a heavy metal. [EU] Tonic: 1. Producing and restoring the normal tone. 2. Characterized by continuous tension. 3. A term formerly used for a class of medicinal preparations believed to have the power of restoring normal tone to tissue. [EU] Tooth Preparation: Procedures carried out with regard to the teeth or tooth structures preparatory to specified dental therapeutic and surgical measures. [NIH] Topical: On the surface of the body. [NIH] Torsion: A twisting or rotation of a bodily part or member on its axis. [NIH] Toxic: Having to do with poison or something harmful to the body. Toxic substances usually cause unwanted side effects. [NIH] Toxicity: The quality of being poisonous, especially the degree of virulence of a toxic microbe or of a poison. [EU] Toxicology: The science concerned with the detection, chemical composition, and pharmacologic action of toxic substances or poisons and the treatment and prevention of toxic manifestations. [NIH]
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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] Toxoplasmosis: The acquired form of infection by Toxoplasma gondii in animals and man. [NIH]
Trachea: The cartilaginous and membranous tube descending from the larynx and branching into the right and left main bronchi. [NIH] Trachoma: A chronic infection of the conjunctiva and cornea caused by Chlamydia trachomatis. [NIH] 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] Transfer Factor: Factor derived from leukocyte lysates of immune donors which can transfer both local and systemic cellular immunity to nonimmune recipients. [NIH] Transferases: Transferases are enzymes transferring a group, for example, the methyl group or a glycosyl group, from one compound (generally regarded as donor) to another compound (generally regarded as acceptor). The classification is based on the scheme "donor:acceptor group transferase". (Enzyme Nomenclature, 1992) EC 2. [NIH] Transforming Growth Factor beta: A factor synthesized in a wide variety of tissues. It acts synergistically with TGF-alpha in inducing phenotypic transformation and can also act as a negative autocrine growth factor. TGF-beta has a potential role in embryonal development, cellular differentiation, hormone secretion, and immune function. TGF-beta is found mostly as homodimer forms of separate gene products TGF-beta1, TGF-beta2 or TGF-beta3. Heterodimers composed of TGF-beta1 and 2 (TGF-beta1.2) or of TGF-beta2 and 3 (TGFbeta2.3) have been isolated. The TGF-beta proteins are synthesized as precursor proteins. [NIH]
Transgenes: Genes that are introduced into an organism using gene transfer techniques. [NIH]
Translating: Conversion from one language to another language. [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]
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Transposons: Discrete genetic elements capable of inserting, in a non-permuted fashion, into the chromosomes of many bacteria. [NIH] Trauma: Any injury, wound, or shock, must frequently physical or structural shock, producing a disturbance. [NIH] Treatment Failure: A measure of the quality of health care by assessment of unsuccessful results of management and procedures used in combating disease, 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 no attempt at voluntary movement, and occurs as a relatively frequent manifestation of Parkinson disease. [NIH] Trichomoniasis: An infection with the protozoan parasite Trichomonas vaginalis. [NIH] Tricuspid Atresia: Absence of the orifice between the right atrium and ventricle, with the presence of an atrial defect through which all the systemic venous return reaches the left heart. As a result, there is left ventricular hypertrophy because the right ventricle is absent or not functional. [NIH] Triglyceride: A lipid carried through the blood stream to tissues. Most of the body's fat tissue is in the form of triglycerides, stored for use as energy. Triglycerides are obtained primarily from fat in foods. [NIH] Trimethoprim-sulfamethoxazole: An antibiotic drug used to treat infection and prevent pneumocystis carinii pneumonia. [NIH] Trophic: Of or pertaining to nutrition. [EU] Tropism: Directed movements and orientations found in plants, such as the turning of the sunflower to face the sun. [NIH] Trypsin: A serine endopeptidase that is formed from trypsinogen in the pancreas. It is converted into its active form by enteropeptidase in the small intestine. It catalyzes hydrolysis of the carboxyl group of either arginine or lysine. EC 3.4.21.4. [NIH] Tryptophan: An essential amino acid that is necessary for normal growth in infants and for nitrogen balance in adults. It is a precursor serotonin and niacin. [NIH] 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 model: A type of animal model which can be used to study the development and progression of diseases and to test new treatments before they are given to humans. Animals with transplanted human cancers or other tissues are called xenograft models. [NIH] Tumor Necrosis Factor: Serum glycoprotein produced by activated macrophages and other mammalian mononuclear leukocytes which has necrotizing activity against tumor cell lines and increases ability to reject tumor transplants. It mimics the action of endotoxin but differs from it. It has a molecular weight of less than 70,000 kDa. [NIH] Tumor suppressor gene: Genes in the body that can suppress or block the development of cancer. [NIH] Tumorigenic: Chemical, viral, radioactive or other agent that causes cancer; carcinogenic. [NIH]
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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] Tunica: A rather vague term to denote the lining coat of hollow organs, tubes, or cavities. [NIH]
Typhimurium: Microbial assay which measures his-his+ reversion by chemicals which cause base substitutions or frameshift mutations in the genome of this organism. [NIH] 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] Ubiquitin: A highly conserved 76 amino acid-protein found in all eukaryotic cells. [NIH] Ulcer: A localized necrotic lesion of the skin or a mucous surface. [NIH] Ulceration: 1. The formation or development of an ulcer. 2. An ulcer. [EU] Ulna: The long and medial bone of the forearm. [NIH] Ultraviolet radiation: Invisible rays that are part of the energy that comes from the sun. UV radiation can damage the skin and cause melanoma and other types of skin cancer. UV radiation that reaches the earth's surface is made up of two types of rays, called UVA and UVB rays. UVB rays are more likely than UVA rays to cause sunburn, but UVA rays pass deeper into the skin. Scientists have long thought that UVB radiation can cause melanoma and other types of skin cancer. They now think that UVA radiation also may add to skin damage that can lead to skin cancer and cause premature aging. For this reason, skin specialists recommend that people use sunscreens that reflect, absorb, or scatter both kinds of UV radiation. [NIH] Unconscious: Experience which was once conscious, but was subsequently rejected, as the "personal unconscious". [NIH] Uncoupling Agents: Chemical agents that uncouple oxidation from phosphorylation in the metabolic cycle so that ATP synthesis does not occur. Included here are those ionophores that disrupt electron transfer by short-circuiting the proton gradient across mitochondrial membranes. [NIH] Uracil: An anticancer drug that belongs to the family of drugs called alkylating agents. [NIH] Uraemia: 1. An excess in the blood of urea, creatinine, and other nitrogenous end products of protein and amino acids metabolism; more correctly referred to as azotemia. 2. In current usage the entire constellation of signs and symptoms of chronic renal failure, including nausea, vomiting anorexia, a metallic taste in the mouth, a uraemic odour of the breath, pruritus, uraemic frost on the skin, neuromuscular disorders, pain and twitching in the muscles, hypertension, edema, mental confusion, and acid-base and electrolyte imbalances. [EU]
Urea: A compound (CO(NH2)2), formed in the liver from ammonia produced by the deamination of amino acids. It is the principal end product of protein catabolism and constitutes about one half of the total urinary solids. [NIH] Urea Breath Test: A test used to detect Helicobacter pylori infection. The test measures breath samples for urease, an enzyme H. pylori makes. [NIH] Urease: An enzyme that catalyzes the conversion of urea and water to carbon dioxide and ammonia. EC 3.5.1.5. [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]
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Urethra: The tube through which urine leaves the body. It empties urine from the bladder. [NIH]
Urethritis: Inflammation of the urethra. [EU] 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] Uridine Diphosphate: A uracil nucleotide containing a pyrophosphate group esterified to C5 of the sugar moiety. [NIH] Urinary: Having to do with urine or the organs of the body that produce and get rid of urine. [NIH] Urinary tract: The organs of the body that produce and discharge urine. These include the kidneys, ureters, bladder, and urethra. [NIH] Urinary tract infection: An illness caused by harmful bacteria growing in the urinary tract. [NIH]
Urine: Fluid containing water and waste products. Urine is made by the kidneys, stored in the bladder, and leaves the body through the urethra. [NIH] Urogenital: Pertaining to the urinary and genital apparatus; genitourinary. [EU] Urticaria: A vascular reaction of the skin characterized by erythema and wheal formation due to localized increase of vascular permeability. The causative mechanism may be allergy, infection, or stress. [NIH] Uterus: The small, hollow, pear-shaped organ in a woman's pelvis. This is the organ in which a fetus develops. Also called the womb. [NIH] Vaccination: Administration of vaccines to stimulate the host's immune response. This includes any preparation intended for active immunological prophylaxis. [NIH] Vaccine: A substance or group of substances meant to cause the immune system to respond to a tumor or to microorganisms, such as bacteria or viruses. [NIH] Vaccinia: The cutaneous and occasional systemic reactions associated with vaccination using smallpox (variola) vaccine. [NIH] Vaccinia Virus: The type species of Orthopoxvirus, related to cowpox virus, but whose true origin is unknown. It has been used as a live vaccine against smallpox. It is also used as a vector for inserting foreign DNA into animals. Rabbitpox virus is a subspecies of vaccinia virus. [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] Vaginitis: Inflammation of the vagina characterized by pain and a purulent discharge. [NIH] Vaginosis: A condition caused by the overgrowth of anaerobic bacteria (e. g., Gardnerella vaginalis), resulting in vaginal irritation and discharge. [NIH] Varicose: The common ulcer in the lower third of the leg or near the ankle. [NIH] Varicose vein: An abnormal swelling and tortuosity especially of the superficial veins of the legs. [EU] Variola: A generalized virus infection with a vesicular rash. [NIH] Vascular: Pertaining to blood vessels or indicative of a copious blood supply. [EU]
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Vascular endothelial growth factor: VEGF. A substance made by cells that stimulates new blood vessel formation. [NIH] Vasculitis: Inflammation of a blood vessel. [NIH] Vasodilator: An agent that widens blood vessels. [NIH] VE: The total volume of gas either inspired or expired in one minute. [NIH] Vector: Plasmid or other self-replicating DNA molecule that transfers DNA between cells in nature or in recombinant DNA technology. [NIH] Vein: Vessel-carrying blood from various parts of the body to the heart. [NIH] Venereal: Pertaining or related to or transmitted by sexual contact. [EU] Venous: Of or pertaining to the veins. [EU] Venous Thrombosis: The formation or presence of a thrombus within a vein. [NIH] Ventilation: 1. In respiratory physiology, the process of exchange of air between the lungs and the ambient air. Pulmonary ventilation (usually measured in litres per minute) refers to the total exchange, whereas alveolar ventilation refers to the effective ventilation of the alveoli, in which gas exchange with the blood takes place. 2. In psychiatry, verbalization of one's emotional problems. [EU] Ventricle: One of the two pumping chambers of the heart. The right ventricle receives oxygen-poor blood from the right atrium and pumps it to the lungs through the pulmonary artery. The left ventricle receives oxygen-rich blood from the left atrium and pumps it to the body through the aorta. [NIH] Ventricular: Pertaining to a ventricle. [EU] Ventricular Remodeling: The geometric and structural changes that the ventricle undergoes, usually following myocardial infarction. It comprises expansion of the infarct and dilatation of the healthy ventricle segments. While most prevalent in the left ventricle, it can also occur in the right ventricle. [NIH] Venules: The minute vessels that collect blood from the capillary plexuses and join together to form veins. [NIH] Vertebrae: A bony unit of the segmented spinal column. [NIH] Vesicular: 1. Composed of or relating to small, saclike bodies. 2. Pertaining to or made up of vesicles on the skin. [EU] Vestibular: Pertaining to or toward a vestibule. In dental anatomy, used to refer to the tooth surface directed toward the vestibule of the mouth. [EU] Veterinary Medicine: The medical science concerned with the prevention, diagnosis, and treatment of diseases in animals. [NIH] Vibrio: A genus of Vibrionaceae, made up of short, slightly curved, motile, gram-negative rods. Various species produce cholera and other gastrointestinal disorders as well as abortion in sheep and cattle. [NIH] Vibrio cholerae: The etiologic agent of cholera. [NIH] Villous: Of a surface, covered with villi. [NIH] Villus: Cell found in the lining of the small intestine. [NIH] Viral: Pertaining to, caused by, or of the nature of virus. [EU] Viral Proteins: Proteins found in any species of virus. [NIH] Viral vector: A type of virus used in cancer therapy. The virus is changed in the laboratory and cannot cause disease. Viral vectors produce tumor antigens (proteins found on a tumor
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cell) and can stimulate an antitumor immune response in the body. Viral vectors may also be used to carry genes that can change cancer cells back to normal cells. [NIH] Virion: The infective system of a virus, composed of the viral genome, a protein core, and a protein coat called a capsid, which may be naked or enclosed in a lipoprotein envelope called the peplos. [NIH] Virulence: The degree of pathogenicity within a group or species of microorganisms or viruses as indicated by case fatality rates and/or the ability of the organism to invade the tissues of the host. [NIH] Virulent: A virus or bacteriophage capable only of lytic growth, as opposed to temperate phages establishing the lysogenic response. [NIH] Virus: Submicroscopic organism that causes infectious disease. In cancer therapy, some viruses may be made into vaccines that help the body build an immune response to, and kill, tumor cells. [NIH] Virus Replication: The process of intracellular viral multiplication, consisting of the synthesis of proteins, nucleic acids, and sometimes lipids, and their assembly into a new infectious particle. [NIH] Viscosity: A physical property of fluids that determines the internal resistance to shear forces. [EU] Vital Capacity: The volume of air that is exhaled by a maximal expiration following a maximal inspiration. [NIH] Vitreous: Glasslike or hyaline; often used alone to designate the vitreous body of the eye (corpus vitreum). [EU] Vitreous Body: The transparent, semigelatinous substance that fills the cavity behind the crystalline lens of the eye and in front of the retina. It is contained in a thin hyoid membrane and forms about four fifths of the optic globe. [NIH] Vitreous Hemorrhage: Hemorrhage into the vitreous body. [NIH] Vitro: Descriptive of an event or enzyme reaction under experimental investigation occurring outside a living organism. Parts of an organism or microorganism are used together with artificial substrates and/or conditions. [NIH] Vivo: Outside of or removed from the body of a living organism. [NIH] Vulnerary: A mixture of vinegar, alcohol, dilute sulphuric acid, honey, and water; at one time used in the treatment of wounds. [NIH] Warfarin: An anticoagulant that acts by inhibiting the synthesis of vitamin K-dependent coagulation factors. Warfarin is indicated for the prophylaxis and/or treatment of venous thrombosis and its extension, pulmonary embolism, and atrial fibrillation with embolization. It is also used as an adjunct in the prophylaxis of systemic embolism after myocardial infarction. Warfarin is also used as a rodenticide. [NIH] White blood cell: A type of cell in the immune system that helps the body fight infection and disease. White blood cells include lymphocytes, granulocytes, macrophages, and others. [NIH]
Windpipe: A rigid tube, 10 cm long, extending from the cricoid cartilage to the upper border of the fifth thoracic vertebra. [NIH] 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]
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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] Xenobiotics: Chemical substances that are foreign to the biological system. They include naturally occurring compounds, drugs, environmental agents, carcinogens, insecticides, etc. [NIH]
Xenograft: The cells of one species transplanted to another species. [NIH] X-ray: High-energy radiation used in low doses to diagnose diseases and in high doses to treat cancer. [NIH] 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]
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INDEX 1 1-Methyl-4-phenylpyridinium, 222, 267 A Abdomen, 267, 280, 286, 322, 326, 343, 344, 364, 365 Abdominal, 33, 202, 254, 267, 269, 297, 307, 327, 341, 342, 344 Aberrant, 8, 28, 50, 58, 267 Ablate, 63, 267 Ablation, 36, 63, 69, 95, 267 Abortion, 267, 374 Abrasion, 227, 267 Abscess, 224, 226, 267, 312 Acceptor, 267, 325, 341, 368, 370 Acetaminophen, 220, 267 Acetylcholine, 267, 287, 337 Acidity, 267, 345 Acidosis, 114, 268 Acne, 90, 108, 116, 119, 124, 129, 151, 158, 205, 219, 220, 228, 251, 268, 358 Acne Rosacea, 205, 268 Acne Vulgaris, 116, 124, 129, 158, 268 Acremonium, 268, 285 Acrodermatitis, 129, 268 Acrodynia, 226, 268 Actin, 38, 51, 52, 56, 61, 268, 309, 331, 333, 334, 336 Actinin, 268, 300 Actinomycosis, 214, 268 Acute leukemia, 28, 268 Acute lymphoblastic leukemia, 20, 268 Acute lymphocytic leukemia, 268 Acute myelogenous leukemia, 28, 58, 268 Acute myeloid leukemia, 268 Acute nonlymphocytic leukemia, 268 Acyl, 11, 176, 268 Acyl Carrier Protein, 11, 268 Adaptability, 268, 285 Adaptation, 53, 173, 269, 347 Adenine, 136, 269, 353 Adenocarcinomas, 10, 269 Adenoma, 63, 269 Adenovirus, 15, 16, 21, 26, 52, 75, 87, 88, 93, 269, 358 Adenylate Cyclase, 269, 287 Adhesives, 269, 328 Adipocytes, 269, 291 Adipose Tissue, 50, 269
Adjustment, 269 Adjuvant, 155, 190, 192, 198, 208, 269, 309 Adoptive Transfer, 27, 269 Adrenal Cortex, 40, 269, 293, 304, 350, 356 Adrenergic, 269, 274, 298, 304, 350, 366 Adsorption, 197, 209, 269 Adsorptive, 269 Adverse Effect, 5, 182, 228, 232, 269, 357, 362 Aerobic, 77, 269, 317, 332, 359, 364 Afferent, 269, 321 Affinity, 23, 48, 151, 154, 178, 208, 213, 269, 270, 276, 325, 330, 362 Affinity Chromatography, 151, 154, 270 Agar, 80, 270, 294, 318, 346 Age Groups, 101, 270 Aged, 80 and Over, 270 Agenesis, 226, 270 Agonist, 51, 270, 298, 304, 355 Albumin, 145, 148, 270, 346 Aldehydes, 54, 270, 376 Algorithms, 270, 279 Alimentary, 3, 99, 100, 120, 122, 270, 342 Alkaline, 268, 270, 271, 277, 282 Alkaloid, 270, 353, 357 Alleles, 32, 270 Allograft, 38, 270 Allopurinol, 174, 270 Alloys, 270, 341 Alopecia, 271, 294 Alpha Particles, 271, 354 Alternative medicine, 143, 160, 230, 271 Aluminum, 271, 366 Alveolitis, 87, 271 Amaurosis, 55, 271 Amebiasis, 271, 330 Ameliorating, 45, 271 Amelogenesis Imperfecta, 226, 227, 271 Amine, 271, 315 Amino acid, 46, 166, 207, 271, 273, 275, 276, 283, 289, 290, 293, 294, 297, 298, 304, 305, 310, 311, 315, 316, 324, 327, 330, 339, 343, 345, 346, 348, 350, 351, 358, 361, 366, 368, 369, 370, 371, 372 Amino Acid Sequence, 166, 271, 273, 290, 305, 310, 350 Amino Acids, 207, 271, 273, 283, 304, 310, 330, 339, 343, 348, 351, 358, 361, 370, 372
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Tetracycline
Amino-terminal, 271, 350 Ammonia, 271, 372 Amoxicillin, 68, 74, 81, 134, 135, 144, 159, 228, 247 Ampicillin, 9, 81, 87, 108, 111, 249, 271 Amplification, 19, 66, 83, 271 Amyloid, 8, 43, 201, 272 Anabolic, 189, 220, 221, 272 Anaemia, 203, 272, 328 Anaerobic, 74, 83, 272, 317, 334, 364, 373 Anaesthesia, 102, 272, 319 Anal, 48, 151, 154, 272, 307 Analgesic, 220, 267, 272, 317, 335, 353 Analog, 17, 67, 85, 183, 188, 230, 272, 289 Analogous, 61, 179, 212, 272, 299, 347, 370 Anaphylatoxins, 272, 290 Anaplasia, 272 Anaplasmosis, 136, 272 Anatomical, 272, 276, 286, 301, 318, 331, 360 Anchorage, 6, 272 Androgens, 97, 269, 272, 293 Anemia, 107, 124, 272, 282, 307, 327 Aneurysm, 34, 184, 202, 272, 275 Angina, 272, 350 Angina Pectoris, 272, 350 Anginal, 272, 337 Angiogenesis, 27, 29, 30, 35, 166, 272, 273, 328 Angiogenesis inhibitor, 166, 273 Angiography, 61, 273 Angioplasty, 55, 273, 334 Angiotensinogen, 273, 356 Animal model, 15, 17, 22, 38, 49, 181, 222, 273, 371 Anionic, 197, 208, 273, 363 Anions, 270, 273, 322, 361, 366 Annealing, 273, 348 Anomalies, 226, 273 Anorexia, 246, 273, 340, 372 Anterior chamber, 273, 322 Anthrax, 221, 251, 255, 273 Antiandrogens, 97, 273 Antibiotics, Aminoglycoside, 207, 273 Antibodies, 23, 24, 31, 170, 192, 213 Antibody, 42, 192, 213, 270, 273, 274, 280, 290, 304, 313, 315, 318, 319, 323, 328, 332, 354, 363, 376 Anticoagulant, 274, 351, 375 Antifungal, 173, 210, 214, 274 Antifungal Agents, 214, 274 Antigen, 58, 170, 192, 213
Antigen-Antibody Complex, 274, 290 Antigen-presenting cell, 274, 296 Antihypertensive, 274, 357 Anti-infective, 168, 274, 287, 316 Anti-inflammatory, 17, 43, 49, 89, 168, 180, 189, 248, 267, 274, 276, 293, 297, 311, 317, 319, 335, 349 Anti-Inflammatory Agents, 49, 180, 274, 276, 293 Antimetabolite, 274, 330 Antineoplastic, 274, 280, 293, 294, 298, 316, 330, 341 Antioxidant, 67, 167, 189, 220, 274, 276, 341 Antiphlogistic, 208, 274 Antipsychotic, 274, 357 Antipyretic, 267, 275, 335, 353 Antiseptic, 275, 322 Antiviral, 37, 275, 321 Anus, 272, 275, 280, 290, 344 Anxiety, 275, 350 Aorta, 202, 275, 374 Aortic Aneurysm, 33, 128, 202, 275 Aplasia, 226, 275, 300 Apolipoproteins, 275, 325 Apoptosis, 8, 13, 18, 20, 22, 24, 29, 30, 34, 37, 41, 43, 47, 52, 61 Aqueous, 177, 179, 199, 200, 210, 275, 277, 295, 301, 316, 324, 363 Arachidonic Acid, 176, 275, 300, 324, 351 Archaea, 275, 331 Arginine, 213, 272, 275, 337, 371 Aromatic, 11, 275, 283, 330, 345 Arterial, 55, 275, 281, 283, 287, 292, 316, 351, 367 Arteries, 202, 275, 276, 280, 283, 286, 293, 323, 326, 330, 334, 353, 368 Arterioles, 275, 280, 282, 334 Arteriosus, 276, 353 Artery, 55, 59, 184, 202, 272, 273, 275, 276, 283, 293, 301, 302, 323, 331, 334, 353, 356 Articular, 276, 340 Ascorbic Acid, 138, 140, 156, 276, 316 Aseptic, 276, 339, 364 Aspartate, 13, 46, 56, 70, 276 Aspergillosis, 214, 276 Aspirin, 180, 189, 276 Assay, 11, 15, 32, 56, 63, 76, 80, 144, 145, 276, 372 Astringents, 276, 330 Astrocytes, 36, 43, 276, 327, 331 Asymptomatic, 43, 271, 276, 312, 342
379
Atrial, 276, 292, 371, 375 Atrial Fibrillation, 276, 375 Atrioventricular, 276, 292 Atrium, 276, 292, 371, 374 Atrophic Gastritis, 228, 276 Atrophy, 200, 267, 276, 336 Attenuated, 169, 170, 191, 192, 193, 215, 276, 297 Auditory, 276, 313, 359 Autacoids, 276, 319 Autodigestion, 277, 342 Autoimmune disease, 9, 180, 277, 333 Autonomic, 267, 275, 277, 338, 344 Axons, 277, 336, 339, 344 Azithromycin, 10, 64, 68, 74, 100, 108, 120, 123, 225, 277 B Babesiosis, 277, 353 Bacillus, 82, 83, 211, 221, 273, 277, 300 Bacteraemia, 97, 277, 312 Bacterial Infections, 39, 156, 165, 184, 199, 204, 207, 209, 277 Bacterial Physiology, 9, 269, 277 Bacterial Proteins, 9, 277 Bactericidal, 4, 126, 277, 338 Bacteriophage, 277, 320, 346, 370, 375 Bacteriophage lambda, 277, 320 Bacteriostatic, 4, 165, 167, 191, 277, 304 Bacterium, 207, 247, 277, 279, 339, 352, 356, 361, 367 Barium, 148, 277 Base, 54, 91, 173, 176, 197, 209, 253, 269, 277, 296, 308, 310, 323, 347, 367, 372 Base Sequence, 277, 308, 310 Basement Membrane, 31, 33, 169, 278, 305, 324 Basophils, 216, 278, 313, 324 Benign, 218, 269, 278, 308, 313, 335, 337, 342, 354, 359, 369 Benzene, 209, 278 Benzoic Acid, 162, 278 Beta-Galactosidase, 75, 278 Beta-Lactamases, 278, 284, 317 Beta-pleated, 272, 278 Bilateral, 90, 278, 357 Bile, 225, 278, 308, 314, 316, 326, 365, 366 Bile Acids, 278, 365 Bile Acids and Salts, 278 Biliary, 278, 314, 342 Biliary Tract, 278, 342 Bilirubin, 270, 278 Binding agent, 197, 278
Binding Sites, 213, 278 Bioavailability, 91, 112, 135, 278 Biological response modifier, 278, 279, 321 Biological therapy, 279, 313 Biological Transport, 279, 297 Bioluminescence, 279, 326 Biomarkers, 7, 279 Biopsy, 123, 248, 279, 344 Bioreactors, 135, 279 Biosynthesis, 11, 45, 75, 267, 275, 279, 361 Biotechnology, 64, 86, 124, 134, 181, 212, 230, 241, 279 Bismuth, 3, 71, 73, 91, 99, 100, 107, 135, 171, 228, 234, 247, 279 Bismuth Subsalicylate, 107, 234, 247, 279 Bivalent, 104, 279, 330 Bladder, 279, 291, 294, 333, 351, 372, 373 Blastocyst, 279, 291, 346 Blastomyces, 279, 342 Blastomycosis, 214, 279 Blennorrhoea, 279, 312 Bleomycin, 30, 92, 230, 280 Blepharitis, 179, 206, 280 Blister, 280, 343 Blood Coagulation, 280, 282, 368 Blood Glucose, 182, 280, 314, 320 Blood Platelets, 145, 280, 361 Blood pressure, 274, 280, 283, 316, 332, 337, 353, 363 Blood-Brain Barrier, 280, 325 Blot, 280, 317 Blotting, Western, 280, 317 Blushing, 247, 280 Body Burden, 280, 324 Body Fluids, 279, 280, 282, 299, 362, 371 Bone Density, 35, 280 Bone Marrow, 22, 174, 210, 268, 278, 280, 310, 317, 326, 334, 363, 365 Bone Marrow Transplantation, 22, 174, 210, 280 Bone Resorption, 88, 280, 344 Bowel, 53, 168, 176, 180, 219, 246, 251, 272, 280, 297, 303, 319, 322, 324, 344, 362, 365 Bowel Movement, 280, 297, 365 Brachytherapy, 281, 321, 323, 354, 376 Bradykinin, 281, 337, 347 Brain Hypoxia, 281 Brain Infarction, 281 Brain Ischemia, 85, 281 Brain Stem, 281, 336 Branch, 263, 281, 327, 343, 352, 363, 366, 368
380
Tetracycline
Breakdown, 183, 281, 297, 308, 339 Breath Tests, 247, 281 Breeding, 38, 281 Broad-spectrum, 108, 167, 271, 281, 284, 285, 300 Bronchi, 281, 304, 370 Bronchial, 281, 315, 351 Bronchitis, 94, 158, 281, 288 Bronchopulmonary, 59, 281 Bronchopulmonary Dysplasia, 59, 281 Brucellosis, 68, 281 Buccal, 281, 326, 365 Bullous, 92, 93, 105, 115, 248, 281 Bupivacaine, 281, 325 Burns, 121, 281 Burns, Electric, 281 Butyric Acid, 209, 281 Bypass, 282, 334 C Cachexia, 41, 282 Cadherins, 23, 282 Cadmium, 106, 282 Cadmium Poisoning, 282 Calcification, 152, 282 Calcium Hydroxide, 102, 282 Callus, 282, 301 Calmodulin, 37, 56, 221, 282 Candidiasis, 43, 80, 214, 282 Candidosis, 282 Cannula, 167, 282 Capillary, 153, 172, 216, 281, 282, 283, 359, 374 Capillary Permeability, 216, 281, 283 Capping, 53, 283 Capsid, 283, 338, 375 Capsules, 100, 202, 283, 298, 309 Captopril, 195, 283 Carbohydrate, 182, 225, 283, 293, 311, 312, 348, 361 Carbon Dioxide, 283, 295, 307, 346, 357, 372 Carboxy, 188, 283 Carboxylic Acids, 209, 283 Carcinogen, 283, 330, 333 Carcinogenesis, 223, 283, 286, 346 Carcinogenic, 278, 283, 320, 338, 339, 350, 365, 371 Carcinoma, 57, 177, 283 Cardiac, 16, 28, 38, 61, 184 Cardiac arrest, 184, 283 Cardiomyopathy, 28, 38, 61, 283 Cardioselective, 283, 350
Carotene, 283, 357 Carotid Arteries, 202, 283 Case report, 88, 107, 110, 122, 128, 283, 289 Caspase, 13, 24, 25, 49, 284 Cataract, 201, 284 Catecholamine, 284, 298 Catfish, 149, 284 Catheter, 202, 284, 302 Catheterization, 273, 284, 334 Cathode, 284, 305 Cations, 104, 150, 155, 157, 284, 322 Caudal, 284, 297, 348 Causality, 61, 284 Cause of Death, 44, 284 Cefixime, 124, 284 Cefotaxime, 68, 284 Ceftazidime, 9, 284 Ceftriaxone, 68, 74, 80, 284 Celiac Disease, 53, 284 Cell Adhesion, 23, 282, 284, 320 Cell Adhesion Molecules, 23, 284 Cell Aggregation, 285, 340 Cell Cycle, 10, 29, 38, 41, 42, 46, 50, 52, 55, 57, 63, 88, 129, 285, 294, 352 Cell Death, 12, 20, 25, 32, 34, 37, 49, 63, 78, 167, 267, 275, 285, 335 Cell Differentiation, 18, 285, 362 Cell Division, 50, 277, 285, 313, 329, 330, 332, 346, 350, 360 Cell Lineage, 16, 285 Cell membrane, 203, 279, 285, 296, 300, 305, 322, 329, 345 Cell motility, 52, 285 Cell Physiology, 53, 89, 285 Cell proliferation, 16, 29, 31, 51, 56, 178, 285, 321, 358, 362 Cell Respiration, 285, 332, 357 Cell Survival, 33, 285, 313 Cellulitis, 224, 226, 285 Cellulose, 285, 308, 346 Centchroman, 121, 285 Central Nervous System, 7, 36, 49, 190, 201 Cephaloridine, 284, 285 Cephalosporins, 224, 225, 278, 285 Cerebral, 27, 66, 184, 202, 280, 281, 285, 286, 304, 305, 321, 328, 331, 335 Cerebral Arteries, 202, 286, 331 Cerebral Cortex, 286, 305, 321, 335 Cerebrovascular, 183, 184, 286 Cerebrum, 285, 286 Cervical, 106, 286, 359
381
Cervix, 267, 286 Character, 198, 272, 286, 295, 311 Chelating Agents, 180, 286 Chemokines, 13, 286 Chemopreventive, 64, 286 Chemotactic Factors, 89, 286, 290 Chemotaxis, 216, 286 Chemotherapeutic agent, 46, 286 Chemotherapy, 17, 153, 154, 155, 174, 177, 210, 214, 224 Cherubism, 226, 286 Chest cavity, 286, 347, 368 Chest wall, 286, 347 Chimeric Proteins, 181, 286 Chin, 227, 268, 286, 329 Chlamydia, 5, 68, 73, 74, 75, 106, 107, 249, 287, 313, 327, 352, 370 Chlorhexidine, 227, 287 Chlorophyll, 286, 287, 308 Chloroquine, 10, 102, 287 Chlortetracycline, 67, 86, 93, 137, 144, 145, 149, 150, 151, 154, 156, 157, 165, 191, 287 Cholera, 80, 117, 126, 192, 287, 374 Cholera Toxin, 192, 287 Cholesterol, 198, 219, 278, 287, 288, 325, 326, 329, 355, 360, 365 Cholesterol Esters, 287, 325 Cholinergic, 7, 274, 287 Chondrocytes, 178, 287, 306 Chondroitin sulfate, 180, 287 Chorion, 19, 287 Chorioretinitis, 287, 357 Choroid, 287, 292, 357 Choroidal Neovascularization, 30, 287 Chromatin, 54, 275, 287, 303 Chromosomal, 19, 27, 67, 73, 85, 109, 271, 287, 347, 358 Chromosome, 46, 57, 68, 72, 85, 186, 187, 287, 309, 313, 325, 352, 360 Chronic Disease, 246, 282, 288 Chronic Obstructive Pulmonary Disease, 253, 288 Chronic renal, 42, 61, 288, 348, 372 Chylomicrons, 288, 325 Cicatricial, 89, 288 Cilastatin, 288, 317 Ciliary, 98, 276, 288, 333 Ciliary Neurotrophic Factor, 98, 288 Cinchona, 288, 353 Ciprofloxacin, 9, 68, 81, 126, 288 CIS, 19, 53, 56, 63, 185, 288, 357 Citric Acid, 119, 128, 135, 288
Citrus, 135, 276, 288 Clarithromycin, 3, 4, 74, 91, 99, 111, 120, 124, 135, 224, 228, 247, 288 Clavulanic Acid, 68, 288 Clear cell carcinoma, 288, 296 Cleave, 283, 289 Cleft Lip, 226, 289 Clindamycin, 68, 75, 79, 81, 126, 208, 224, 225, 231, 289 Clinical Medicine, 156, 289, 349 Clinical study, 289, 292 Clinical trial, 6, 11, 22, 30, 48, 49, 52, 64, 227, 241, 289, 292, 298, 343, 352, 355 Clone, 48, 213, 289 Cloning, 20, 42, 68, 74, 77, 172, 181, 212, 279, 289, 320 Coagulation, 280, 289, 314, 346, 368, 375 Coal, 278, 289 Coccidioidomycosis, 214, 289 Codons, 84, 207, 289, 310, 339 Coenzyme, 12, 276, 289, 337 Cofactor, 289, 351, 368 Colitis, 72, 289, 319 Collagen, 14, 17, 33, 62, 89, 93, 126, 157, 166, 180, 183, 188, 189, 202, 210, 220, 248, 269, 271, 278, 289, 290, 306, 309, 321, 328, 347, 350 Collagenases, 5, 189, 290 Collapse, 281, 290, 347 Colloidal, 270, 290, 300, 361 Colon, 29, 47, 53, 63, 177, 289, 290, 319, 324, 350 Combination Therapy, 17, 114, 117, 290 Combinatorial, 195, 290 Commensal, 165, 205, 290 Comminuted Fractures, 199, 290 Compacta, 222, 290 Complement, 213, 216, 272, 290, 291, 310, 320, 327, 346 Complement Activation, 216, 272, 290 Complementarity Determining Regions, 213, 290 Complementary and alternative medicine, 143, 160, 290 Complementary medicine, 143, 291 Complementation, 27, 32, 47, 54, 57, 76, 86, 291 Complete remission, 291, 356 Compliance, 10, 111, 134, 135, 291 Computational Biology, 241, 291 Computer Simulation, 47, 291 Conception, 267, 291, 292, 306, 364
382
Tetracycline
Cone, 55, 291, 346, 366 Congenita, 291, 300, 353 Congestive heart failure, 28, 34, 291 Conjugated, 278, 291, 294 Conjunctiva, 179, 291, 319, 323, 329, 370 Conjunctivitis, 165, 179, 205, 291 Connective Tissue Cells, 178, 291 Consciousness, 272, 291, 295, 298 Constitutional, 291, 357 Constriction, 291, 323 Consumption, 291, 296, 338, 357 Contact dermatitis, 228, 292 Contamination, 167, 292 Contraception, 249, 292 Contraceptive, 225, 292 Contraindications, ii, 292 Contralateral, 52, 292 Contrast medium, 273, 292 Controlled clinical trial, 64, 292 Controlled study, 49, 292 Conus, 292, 353 Conventional therapy, 69, 232, 292 Conventional treatment, 292 Coordination, 286, 292, 333 Cor, 31, 292 Cornea, 31, 62, 90, 179, 273, 292, 311, 323, 360, 365, 370 Corneal Stroma, 31, 62, 292 Corneal Ulcer, 90, 183, 292 Corneum, 293, 303 Coronary, 202, 272, 293, 330, 334 Coronary Arteriosclerosis, 293, 334 Coronary Thrombosis, 293, 330, 334 Corpus, 293, 326, 350, 375 Corpus Luteum, 293, 326, 350 Cortex, 40, 156, 293, 315, 331, 340 Cortical, 40, 293, 305 Corticosteroid, 249, 293, 349 Cortisol, 270, 293 Cortisone, 293, 297, 349 Courtship, 56, 293 Cowpox, 293, 373 Cowpox Virus, 293, 373 Cranial, 184, 293, 304, 313, 336, 339, 342, 344 Creatine, 12, 293 Creatinine, 293, 372 Crossing-over, 293, 355 Croton Oil, 293, 345 Cryptococcosis, 214, 294 Cryptosporidiosis, 277, 294 Culture Media, 270, 294
Curative, 10, 294, 358, 368 Curettage, 294, 359 Cutaneous, 93, 116, 121, 124, 129, 158, 273, 279, 282, 292, 294, 312, 323, 326, 373 Cyclic, 12, 204, 226, 269, 282, 294, 313, 337, 345, 348 Cyclin, 41, 46, 50, 55, 58, 294 Cyclophosphamide, 248, 294 Cyst, 23, 106, 114, 294 Cysteine, 8, 75, 112, 213, 286, 294 Cysteinyl, 294, 330 Cystine, 294 Cystitis, 145, 294 Cytochrome, 18, 294, 341 Cytokine, 17, 37, 38, 44, 50, 76, 79, 137, 178, 210, 294 Cytomegalovirus, 26, 83, 214, 294 Cytoplasm, 275, 278, 285, 287, 295, 303, 313, 330, 334, 336, 358, 360 Cytoskeletal Proteins, 61, 295, 299 Cytoskeleton, 6, 37, 53, 295, 320, 331 Cytotoxic, 17, 26, 37, 70, 95, 166, 170, 174, 177, 190, 192, 214, 295, 318, 354, 362 Cytotoxicity, 17, 20, 26, 177, 178, 295 D Databases, Bibliographic, 241, 295 Daunorubicin, 295, 299 De novo, 53, 295 Deamination, 295, 372 Decarboxylation, 295, 315 Decidua, 295, 331, 346 Defense Mechanisms, 295, 320 Degenerative, 7, 57, 180, 222, 292, 295, 327, 340, 358 Dehydration, 174, 210, 287, 295, 361 Dehydroepiandrosterone, 248, 295 Deletion, 54, 62, 63, 67, 275, 295 Demeclocycline, 93, 295 Dementia, 12, 201, 274, 295, 336 Denaturation, 295, 348 Dendrites, 296, 337 Dendritic, 192, 296, 329 Dendritic cell, 192, 296 Dens in Dente, 226, 296 Density, 35, 148, 280, 296, 325, 339, 348 Dental Care, 296, 343 Dental Caries, 296, 307, 363 Dental Plaque, 94, 134, 296 Dentin Dysplasia, 226, 296 Dentists, 224, 296 Depolarization, 296, 362 Dermal, 180, 296, 300
383
Dermatitis, 96, 158, 227, 249, 296 Dermatitis, Contact, 228, 296 Dermatosis, 115, 227, 296 DES, 13, 272, 296 Desmin, 61, 296 Desmosomes, 24, 296 Deuterium, 296, 316 Developing Countries, 296, 327 Developmental Biology, 16, 156, 297 Dexamethasone, 208, 297 Diabetes Mellitus, 182, 225, 297, 311, 314 Diabetic Retinopathy, 166, 297 Diagnostic procedure, 163, 231, 297 Diaphragm, 62, 297, 347 Diarrhea, 4, 177, 228, 246, 271, 279, 294, 297, 307, 327, 361 Diastolic, 297, 316 Diencephalon, 297, 336 Dietary Fats, 297, 325 Diffusion, 80, 83, 209, 279, 283, 297, 318, 319, 322 Digestion, 268, 270, 278, 280, 297, 319, 322, 325, 326, 343, 365, 373 Digestive system, 171, 297, 333 Digestive tract, 297, 362 Dilatation, 202, 267, 272, 273, 297, 349, 374 Dilated cardiomyopathy, 28, 61, 297 Dilution, 80, 297 Dimerization, 208, 297 Dimethyl, 144, 150, 297 Dimethyl Sulfoxide, 144, 150, 297 Diploid, 291, 298, 346 Direct, iii, 15, 24, 29, 60, 63, 80, 165, 181, 191, 232, 233 Discrete, 14, 46, 298, 351, 371 Disease Progression, 22, 49, 55, 298 Dissociation, 270, 298 Distal, 59, 62, 110, 176, 298, 324, 352 Dopa, 298, 325 Dopamine, 222, 267, 274, 298, 325, 337, 345 Dopamine Agonists, 222, 298 Dorsal, 32, 298, 336, 348, 364 Dosage Forms, 210, 215, 298 Dose-limiting, 174, 210, 298 Double-blind, 48, 49, 80, 87, 91, 98, 120, 298 Doxorubicin, 11, 17, 298 Drive, ii, vi, 16, 18, 25, 47, 51, 133, 224, 225, 226, 227, 228, 299, 322, 325 Drug Combinations, 11, 299 Drug Design, 39, 195, 299 Drug Interactions, 232, 234, 299
Drug Resistance, 17, 28, 118, 299 Drug Tolerance, 299, 369 Drusen, 167, 299 Duct, 114, 282, 284, 299, 341, 359 Duodenal Ulcer, 91, 101, 135, 247, 299 Duodenum, 278, 299, 309, 343, 365 Dura mater, 299, 329, 341 Dyes, 272, 278, 299, 366 Dysmenorrhea, 299, 335 Dysplasia, 59, 61, 226, 227, 299 Dystrophic, 20, 299 Dystrophin, 20, 299 Dystrophy, 20, 62, 299, 300 E Echocardiography, 34, 300 Ectoderm, 300, 336 Ectodermal Dysplasia, 226, 227, 300 Ectopic, 29, 50, 300 Edeine, 70, 300 Edema, 31, 292, 297, 300, 333, 334, 336, 372 Effector, 9, 27, 36, 37, 51, 59, 62, 67, 178, 213, 267, 290, 300, 303, 345 Effector cell, 9, 27, 37, 62, 213, 300 Efferent, 300, 321 Eicosanoids, 176, 300 Elastic, 300, 311, 366 Elastin, 289, 300, 306 Electrolysis, 273, 284, 300 Electrolyte, 293, 300, 332, 349, 363, 372 Electrophoresis, 19, 153, 300, 318 Electroplating, 300, 366 Electroporation, 26, 300 Electroretinography, 55, 301 Emboli, 301, 375 Embolism, 301, 353, 375 Embolization, 301, 375 Embolus, 184, 301, 319 Embryo, 32, 267, 279, 285, 300, 301, 319, 330, 340, 347 Embryogenesis, 16, 166, 301 Embryology, 301, 337 Emollient, 301, 311, 338 Emphysema, 288, 301 Empirical, 14, 301 Empyema, 301, 368 Emulsion, 301, 307 Enamel, 97, 149, 226, 271, 296, 301, 307, 323 Enamel Microabrasion, 226, 301 Encapsulated, 301, 326 Encephalitis, 43, 301, 302 Encephalitis, Viral, 301, 302
384
Tetracycline
Endarterectomy, 273, 302 Endemic, 64, 100, 128, 287, 302, 327, 364 Endocarditis, 209, 282, 302, 312 Endocardium, 302 Endocytosis, 22, 52, 302 Endodontics, 102, 115, 136, 302 Endometrium, 295, 302, 329, 331 Endoscopy, 4, 247, 302 Endothelial cell, 27, 30, 44, 51, 56, 166, 216, 280, 302, 306, 368 Endothelium, 60, 63, 216, 302, 337 Endothelium, Lymphatic, 302 Endothelium, Vascular, 302 Endothelium-derived, 302, 337 Endotoxemia, 76, 302 Endotoxic, 79, 302 Endotoxin, 44, 302, 371 End-stage renal, 288, 302, 348 Enhancer, 7, 13, 62, 303, 357 Enteritis, 255, 303 Enterocolitis, 303 Enteropeptidase, 303, 371 Environmental Exposure, 303, 339 Environmental Health, 53, 240, 242, 303 Enzymatic, 53, 218, 271, 282, 283, 290, 296, 303, 306, 315, 329, 348, 357 Enzyme Induction, 303, 356 Enzyme Inhibitors, 49, 303, 346 Enzyme Repression, 303, 356 Eosinophils, 303, 313, 324 Epidemic, 34, 303, 364 Epidemiological, 73, 108, 303 Epidermal, 33, 303, 323, 329 Epidermal Growth Factor, 33, 303 Epidermal growth factor receptor, 33, 303 Epidermis, 23, 218, 267, 280, 293, 300, 303, 315, 323, 343, 349, 353 Epinephrine, 269, 298, 303, 337, 338, 372 Epistaxis, 304, 352 Epithelial, 6, 10, 22, 31, 33, 52, 57, 59, 62, 104, 148, 189, 200, 206, 221, 269, 279, 287, 292, 295, 303, 304, 312, 324, 342, 344 Epithelial Cells, 6, 22, 57, 59, 62, 104, 148, 269, 287, 303, 304, 324 Epithelium, 30, 31, 60, 63, 167, 200, 278, 296, 302, 304, 309, 322 Epitope, 105, 304 ERV, 242, 304, 305 Erythema, 292, 304, 366, 373 Erythrocytes, 272, 277, 280, 304, 355 Erythromycin, 9, 45, 74, 75, 78, 79, 81, 82, 201, 224, 225
Esophageal, 304, 360 Esophageal Varices, 304, 360 Esophagitis, 304, 366 Esophagus, 297, 304, 314, 343, 345, 355, 365 Estradiol, 6, 304 Estrogen, 6, 35, 174, 248, 304, 350, 355, 360 Estrogen receptor, 6, 174, 248, 304 Estrogen Receptor Modulators, 248, 304 Ethmoid, 168, 219, 304, 342 Etidronate, 248, 304 Eukaryotic Cells, 67, 180, 181, 186, 217, 295, 304, 318, 338, 339, 372 Europium, 115, 151, 154, 305 Evoke, 192, 305, 365 Excitability, 7, 305 Excitation, 12, 28, 305, 337 Excitatory, 305, 311 Excitotoxicity, 49, 305 Excrete, 82, 154, 305 Exfoliation, 226, 305 Exhaustion, 305, 327 Exocytosis, 52, 305 Exogenous, 59, 173, 175, 269, 283, 302, 305, 310, 345, 351 Exon, 40, 305 Exotoxin, 221, 305 Expiration, 305, 357, 375 Expiratory, 304, 305 Expiratory Reserve Volume, 304, 305 Extensor, 305, 352 External-beam radiation, 305, 323, 354, 376 Extracellular, 6, 14, 23, 29, 33, 50, 53, 57, 62, 166, 188 Extracellular Matrix, 6, 14, 57, 62, 166, 188, 291, 305, 306, 320, 328, 340 Extracellular Matrix Proteins, 305, 328 Extracellular Space, 305, 306 Extraction, 144, 147, 306 Extrapyramidal, 275, 298, 306 Eye Infections, 269, 306 F Facial, 227, 306 Family Planning, 241, 306 Fat, 225 Fatigue, 246, 306, 314 Fatty acids, 176, 209, 225, 270, 283, 300, 306, 311, 351, 368 Fatty Liver, 225, 306 Febrile, 306, 328, 364 Femoral, 102, 129, 130, 306
385
Femur, 101, 306 Fertilizers, 306, 366 Fetus, 225, 267, 306, 346, 349, 373 Fibrin, 103, 202, 280, 306, 344, 368 Fibrinogen, 81, 306, 346, 368 Fibrinolytic, 87, 306 Fibroblast Growth Factor, 50, 306 Fibroblasts, 57, 62, 63, 127, 178, 188, 291, 306 Fibrosis, 61, 62, 226, 306, 360 Fistula, 307, 309 Fixation, 197, 202, 307 Flow Injection Analysis, 115, 151, 307 Fluorescence, 17, 47, 51, 54, 76, 120, 131, 144, 145, 147, 154, 307 Fluorine, 307 Fluorosis, 128, 226, 227, 307 Flushing, 247, 307 Folate, 139, 140, 307 Fold, 60, 196, 307 Folic Acid, 138, 139, 140, 246, 307 Follicles, 307, 320 Foodborne Illness, 252, 307 Foramen, 287, 307, 344 Forearm, 280, 307, 354, 372 Fovea, 307 Frameshift, 54, 308, 372 Frameshift Mutation, 308, 372 Free Radicals, 7, 8, 274, 298, 308, 334 Fungi, 168, 183, 208, 211, 219, 274, 276, 279, 306, 308, 313, 321, 331, 334, 364, 368, 376 Fungicides, Industrial, 274, 308 Fungistatic, 278, 308 Fungus, 84, 282, 285, 289, 294, 308, 334 G Galactosides, 278, 308 Galenical, 209, 308 Gallbladder, 267, 278, 297, 308 Gamma Rays, 308, 354 Ganglia, 267, 275, 281, 308, 317, 336, 344 Ganglion, 308, 336, 339 Gas, 271, 283, 297, 304, 307, 308, 316, 319, 327, 333, 337, 347, 374 Gasoline, 278, 308 Gastric, 113, 228, 247, 271, 277, 298, 303, 309, 314, 315, 316, 338, 343, 355, 360 Gastric Juices, 309, 343 Gastric Mucosa, 228, 309 Gastrin, 309, 315 Gastritis, 158, 171, 228, 309, 366 Gastroduodenal, 171, 309
Gastrointestinal tract, 168, 210, 211, 219, 309, 325, 361, 364, 371 Gelatin, 227, 294, 309, 311, 366, 368 Gelatinases, 188, 309 Gels, 106, 227, 309 Gelsolin, 53, 309 Gene, 6, 7, 8, 10, 12, 13, 14, 15, 16, 17, 19, 20, 21, 22, 23, 25, 26, 27, 28, 30, 31, 32, 33, 36, 38, 39, 42, 44, 47, 50, 51, 52, 54, 55, 56, 57, 58, 60, 61, 62, 63, 65, 66, 67, 69, 71, 73, 74, 75, 76, 77, 78, 80, 82, 83, 84, 85, 165, 172, 175, 180, 181, 182, 185, 186, 187, 192, 194, 196, 203, 206, 207, 208, 211, 212, 213, 217, 248 Gene Amplification, 83, 130, 309 Gene Expression Profiling, 10, 309 Gene Fusion, 10, 309 Gene Products, pol, 23, 309 Gene Targeting, 42, 310 Gene-modified, 22, 310 Genetic Code, 310, 338 Genetic Engineering, 11, 279, 289, 310 Genetic Markers, 248, 310 Genetic testing, 310, 348 Genetic transcription, 310, 350, 370 Genetics, 54, 212, 248, 310, 332 Genital, 68, 106, 253, 254, 288, 310, 322, 359, 373 Genitourinary, 5, 249, 250, 310, 373 Genomics, 194, 195, 310 Genotype, 310, 345 Germ Cells, 310, 329, 340, 363, 367 Gestation, 310, 346 Giardiasis, 310, 330 Gingival Recession, 103, 310 Gingivitis, 168, 219, 296, 310 Gland, 179, 200, 206, 269, 293, 311, 326, 341, 346, 351, 355, 360, 365, 366, 368 Glioma, 15, 27, 311 Glomerular, 13, 311, 356 Glomerulus, 62, 311, 324, 335 Glossitis, 226, 311 Glucocorticoid, 187, 297, 311, 331, 349 Glucose, 182, 276, 280, 285, 297, 311, 314, 320, 359 Glucose Intolerance, 297, 311 Glucuronic Acid, 311, 314 Glutamate, 13, 49, 73, 305, 311 Glutamic Acid, 213, 307, 311, 337, 350 Gluten, 284, 311 Glycerol, 176, 282, 311, 345 Glycerophospholipids, 176, 311, 345
386
Tetracycline
Glycine, 213, 271, 278, 311, 337, 361 Glycogen, 179, 182, 287, 311 Glycoprotein, 37, 104, 153, 190, 306, 311, 312, 324, 368, 371 Glycosaminoglycan, 287, 311 Glycosidic, 273, 312 Glycosylation, 81, 125, 312 Goblet Cells, 179, 312 Goiter, 312, 368 Gonad, 312 Gonadal, 40, 312, 364 Gonorrhea, 39, 249, 312, 363 Gonorrhoea, 250, 312 Gout, 312, 335 Governing Board, 312, 349 GP41, 37, 312 Grade, 247, 312 Grading, 101, 312 Graft, 37, 202, 312, 315, 318, 334 Graft Rejection, 312, 318 Gram-negative, 9, 165, 205, 212, 284, 287, 302, 312, 317, 334, 359, 363, 374 Gram-Negative Bacteria, 70, 165, 205, 302, 312, 363 Gram-positive, 77, 165, 205, 211, 212, 312, 317, 364, 365 Gram-Positive Cocci, 77, 313 Granule, 313, 358 Granulocytes, 150, 313, 362, 375 Granuloma, 155, 250, 313, 327, 342 Granuloma Inguinale, 250, 313, 327 Granulosa Cells, 313, 320, 326 Grasses, 307, 313 Growth factors, 31, 36, 62, 201, 313, 331 Guanylate Cyclase, 55, 313, 337 Gyrase, 313, 338 H Habitual, 286, 313 Hair Cells, 24, 313 Hair follicles, 313, 364 Half-Life, 284, 313 Halitosis, 168, 219, 313 Haploid, 313, 346 Haptens, 270, 313 Headache, 313, 319, 352 Health Education, 111, 135, 314 Heart failure, 28, 34, 61, 314 Heartburn, 279, 314, 319 Hematopoiesis, 20, 58, 314 Hematopoietic Stem Cells, 21, 27, 314 Heme, 278, 294, 314, 348 Hemoglobin, 272, 286, 304, 314, 324, 348
Hemoglobin A, 286, 314, 348 Hemoglobinopathies, 310, 314 Hemolysins, 104, 148, 314 Hemopneumothorax, 255, 314 Hemorrhage, 184, 313, 314, 334, 346, 365, 375 Hemorrhoids, 314, 360 Hemostasis, 314, 320, 361 Hemothorax, 314, 368 Heparin, 96, 166, 314 Hepatic, 116, 152, 270, 314, 348 Hepatobiliary, 225, 314 Herbicide, 267, 314 Hereditary, 268, 271, 286, 300, 312, 315, 336, 357 Heredity, 268, 309, 310, 315 Herpes, 21, 127, 172, 186, 187, 315 Herpes Zoster, 315 Herpetiformis, 96, 158, 315 Heterodimers, 315, 320, 370 Heterogeneity, 35, 73, 270, 315 Heterotrophic, 308, 315 Hippocampus, 315, 336 Histamine, 149, 272, 274, 315, 355 Histidine, 315 Histocompatibility, 42, 315 Histology, 4, 35, 38, 315, 336 Histone Deacetylase, 12, 100, 315 Homeobox, 20, 28, 315 Homeostasis, 52, 315 Homodimer, 315, 370 Homogeneous, 81, 125, 315, 345 Homologous, 58, 187, 270, 279, 293, 310, 315, 352, 360, 367 Hormonal, 49, 276, 285, 293, 315 Horny layer, 303, 315 Host, 26, 37, 44, 45, 174, 175, 181, 185, 187, 192, 203, 211, 213, 221, 224 Humoral, 170, 312, 316 Humour, 316 Hybrid, 11, 25, 62, 67, 194, 289, 316 Hybridization, 15, 54, 61, 316, 332 Hybridomas, 301, 316 Hydrochloric Acid, 301, 316 Hydrogen Peroxide, 8, 316, 325, 366 Hydrogenation, 205, 316, 353 Hydrolysis, 278, 284, 316, 322, 345, 348, 352, 371 Hydrophilic, 153, 316 Hydrophobic, 47, 209, 311, 316, 325 Hydroxylysine, 289, 316 Hydroxyproline, 271, 289, 316
387
Hydroxyurea, 46, 316 Hypercalcemia, 304, 316 Hyperglycemia, 182, 316 Hypersensitivity, 177, 316, 325, 358 Hypertension, 59, 167, 195, 198, 313, 316, 350, 372 Hyperthyroidism, 88, 316, 350 Hypertrophy, 61, 292, 317, 358, 371 Hypoglycemia, 182, 317 Hypokinesia, 317, 342 Hypoplasia, 97, 226, 271, 300, 317 Hypoxic, 13, 317, 330 I Ibuprofen, 208, 317 Id, 138, 157, 249, 250, 251, 252, 253, 254, 255, 256, 262, 264, 317 Idiopathic, 28, 222, 268, 317, 359 Iduronidase, 22, 317 Ileum, 157, 317 Imidazole, 315, 317, 355 Imipenem, 9, 75, 288, 317 Immortal, 57, 317 Immune function, 317, 318, 370 Immune Sera, 317 Immune system, 170, 192, 193, 213 Immunity, 168, 193, 216, 219, 317, 318, 370 Immunization, 170, 185, 190, 191, 192, 193, 228, 255, 269, 317, 318 Immunoblotting, 51, 317 Immunocompromised, 9, 214, 317 Immunodeficiency, 152, 169, 193, 318 Immunodiffusion, 270, 318 Immunoelectrophoresis, 270, 318 Immunofluorescence, 52, 318 Immunogenic, 25, 318 Immunoglobulin, 273, 290, 318, 332 Immunohistochemistry, 42, 318 Immunologic, 269, 286, 314, 317, 318, 354 Immunologic Factors, 314, 318 Immunology, 59, 96, 98, 104, 149, 216, 269, 270, 318, 363 Immunosuppressant, 318, 330 Immunosuppressive, 180, 214, 248, 294, 311, 318, 367 Immunosuppressive Agents, 180, 318 Immunosuppressive therapy, 318 Immunotherapy, 27, 269, 279, 318 Impairment, 306, 318, 329, 330 Implant radiation, 318, 321, 323, 354, 376 In situ, 14, 54, 318 In Situ Hybridization, 14, 54, 318 Incidental, 183, 318
Incision, 319, 322 Incisor, 149, 319 Incubation, 53, 221, 319, 324 Incubation period, 221, 319, 324 Indicative, 223, 319, 343, 373 Indigestion, 279, 319 Indomethacin, 208, 319 Induction, 18, 23, 24, 28, 47, 57, 60, 75, 155, 173, 186, 207, 212, 218, 272, 274, 319, 350 Infancy, 319, 358 Infant, Newborn, 270, 319 Infarction, 28, 34, 198, 281, 319, 356 Infiltration, 43, 168, 319, 350 Inflammatory bowel disease, 53, 176, 319 Influenza, 168, 214, 219, 319 Infusion, 319, 334, 360 Ingestion, 273, 282, 313, 319, 347 Inguinal, 320, 327 Inhalation, 221, 289, 320, 347 Inhibin, 40, 320 Initiation, 6, 21, 186, 187, 320, 339, 350, 356, 365, 370 Inlay, 320, 357 Inner ear, 284, 320 Inorganic, 197, 208, 320, 326, 333, 345, 363, 366 Inotropic, 298, 320 Insecticides, 320, 376 Insertional, 181, 320 Insight, 9, 21, 38, 39, 48, 61, 320 Instillation, 116, 320 Insulator, 109, 320, 333 Insulin, 127, 182, 320, 323 Insulin-dependent diabetes mellitus, 320 Integrase, 152, 309, 320 Integrins, 15, 33, 37, 320 Intensive Care, 44, 320 Interferon, 60, 85, 190, 321, 327 Interferon-alpha, 321 Interleukin-1, 178, 321 Interleukin-10, 178, 321 Interleukin-2, 112, 321 Interleukins, 178, 318, 321 Intermediate Filaments, 23, 321, 336 Intermittent, 321, 326, 344 Internal Capsule, 170, 321 Internal Medicine, 37, 59, 114, 116, 134, 228, 321 Internal radiation, 321, 323, 354, 376 Interstitial, 62, 188, 281, 306, 321, 323, 329, 335, 356, 376 Interstitial Collagenase, 188, 321
388
Tetracycline
Intervertebral, 202, 321 Intestinal, 52, 63, 147, 150, 168, 173, 174, 183, 219, 228, 251 Intestinal Flora, 183, 321 Intestinal Mucosa, 147, 284, 303, 321 Intestinal Neoplasms, 63, 321 Intestine, 144, 278, 280, 303, 322, 324, 365 Intracellular, 8, 23, 36, 37, 53, 150, 182, 313, 319, 320, 322, 329, 337, 349, 359, 362, 375 Intracellular Membranes, 322, 329 Intramuscular, 76, 322, 342 Intravenous, 319, 322, 342, 354 Intrinsic, 10, 45, 79, 226, 270, 278, 322 Invasive, 17, 192, 317, 322 Invertebrates, 322, 326 Involuntary, 280, 322, 334, 362, 369 Involution, 134, 322 Iodoquinol, 82, 322 Ion Channels, 276, 322 Ion Transport, 52, 322, 332 Ionizing, 271, 303, 322, 354 Ionophores, 104, 322, 372 Ions, 8, 106, 185, 186, 187, 217, 267, 277, 282, 286, 298, 300, 309, 316, 322, 360 Iris, 31, 273, 276, 292, 322, 353 Irradiation, 128, 323, 376 Irrigation, 119, 227, 323 Irritants, 227, 323 Ischemia, 13, 28, 35, 66, 85, 184, 276, 281, 323, 334, 356 Ischemic stroke, 13, 184, 323 Islet, 182, 323 J Joint, 5, 35, 248, 276, 288, 323, 340, 366, 367 K Kb, 63, 240, 323 Keratan Sulfate, 62, 323 Keratin, 323, 360 Keratinocytes, 24, 33, 218, 220, 323 Keratitis, 179, 206, 323 Kerato, 62, 323 Keratoconjunctivitis, 323, 362 Keratoconjunctivitis Sicca, 323, 362 Kidney Cortex, 324, 330 Kidney Disease, 13, 22, 42, 110, 240, 324 Kinetic, 11, 76, 322, 324, 345 L Labile, 38, 167, 290, 324 Lacrimal, 200, 323, 324, 328, 362 Lacrimal gland, 200, 324 Lactation, 324, 350 Laminin, 6, 30, 31, 57, 278, 306, 324
Large Intestine, 297, 322, 324, 355, 362 Larynx, 89, 324, 370 Latent, 324, 349 Lavage, 145, 324 Laxative, 270, 324 Lead Poisoning, 226, 324 Lens, 31, 63, 284, 291, 324, 375 Lentivirus, 21, 55, 324 Lesion, 25, 60, 279, 313, 324, 326, 359, 361, 369, 372 Lethal, 10, 20, 33, 39, 40, 62, 76, 192, 277, 324, 333 Leucine, 62, 324 Leukemia, 18, 21, 29, 58, 174, 210, 299, 310, 324 Leukocytes, 13, 14, 37, 38, 178, 216, 278, 280, 286, 303, 313, 319, 321, 324, 371 Leukotrienes, 275, 300, 324 Levodopa, 222, 298, 325 Libido, 272, 325 Library Services, 262, 325 Lidocaine, 113, 325 Life cycle, 308, 325 Ligament, 325, 351 Ligands, 52, 181, 195, 207, 284, 320, 325 Lincomycin, 289, 325 Linkage, 51, 73, 283, 310, 325, 343 Lip, 226, 227, 289, 325 Lipase, 53, 83, 155, 325 Lipid, 67, 275, 283, 311, 320, 322, 325, 333, 341, 371 Lipid Peroxidation, 325, 341 Lipophilic, 71, 85, 325 Lipopolysaccharide, 79, 312, 325 Lipoprotein, 148, 312, 325, 326, 375 Liposarcoma, 50, 325 Liposomal, 112, 113, 326 Liver cancer, 52, 326 Localization, 7, 10, 34, 42, 47, 81, 150, 318, 326, 336 Localized, 24, 128, 202, 267, 281, 296, 299, 301, 307, 319, 324, 326, 340, 346, 360, 372, 373 Locomotion, 104, 326, 346 Long-Term Care, 58, 326 Loop, 15, 181, 326 Low-density lipoprotein, 325, 326 Lucida, 324, 326 Lumen, 192, 282, 302, 326 Luminescence, 115, 151, 326 Lupus, 248, 326, 367 Luteal Phase, 326, 331
389
Lutein Cells, 326, 350 Lymph, 192, 286, 302, 316, 326, 327, 342, 359, 360, 366 Lymph node, 192, 286, 326, 342, 359, 360 Lymphatic, 302, 319, 326, 330, 359, 363, 364, 368 Lymphatic system, 326, 359, 363, 364, 368 Lymphoblastic, 20, 327 Lymphoblasts, 268, 327 Lymphocyte, 37, 274, 327, 328 Lymphogranuloma Venereum, 165, 205, 250, 313, 327 Lymphoid, 42, 178, 273, 327 Lymphoma, 72, 177, 228, 247, 327 Lymphoproliferative, 8, 327 Lysine, 46, 316, 327, 350, 371 Lytic, 39, 327, 375 M Macroglia, 327, 331 Macrolides, 45, 81, 167, 327 Macrophage, 13, 45, 321, 327 Macula, 167, 307, 327 Macula Lutea, 327 Macular Degeneration, 30, 166, 167, 327 Major Histocompatibility Complex, 42, 327 Malabsorption, 111, 246, 284, 327, 362 Malabsorption syndrome, 327, 362 Malaise, 281, 327 Malaria, 10, 102, 111, 123, 134, 135, 176, 288, 327, 328 Malaria, Falciparum, 327, 328 Malaria, Vivax, 327, 328 Malignant, 15, 27, 28, 29, 33, 50, 92, 113, 269, 274, 326, 328, 335, 340, 354, 360 Malignant tumor, 269, 328, 340 Malnutrition, 79, 136, 270, 276, 282, 328 Mammary, 40, 49, 328, 355 Mammogram, 282, 328, 331 Mandible, 286, 328, 357 Manifest, 31, 168, 219, 328 Mannans, 308, 328 Mastectomy, 113, 328 Materials Testing, 35, 328 Matrix metalloproteinase, 31, 33, 128, 188, 218, 328 Maxillary, 168, 219, 289, 328, 342 Medial, 289, 304, 328, 372 Mediate, 6, 21, 23, 48, 51, 75, 78, 82, 86, 110, 118, 181, 186, 187, 217, 284, 298, 328, 355 Mediator, 62, 176, 298, 321, 328, 361
MEDLINE, 241, 328 Mefloquine, 10, 328 Megaloblastic, 307, 328 Meibomian, 179, 200, 206, 328, 329 Meibomian Glands, 179, 200, 329 Meiosis, 279, 329, 367 Melanin, 322, 329, 345, 372 Melanocytes, 50, 329, 337 Melanoma, 50, 128, 177, 329, 372 Melanosomes, 329 Membrane Fusion, 23, 329 Membrane Lipids, 329, 345 Membrane Proteins, 329, 352, 363 Memory, 7, 56, 59, 201, 273, 295, 329 Meninges, 284, 285, 299, 329 Meningitis, 116, 312, 329, 346 Menopause, 198, 329, 348, 350 Menstrual Cycle, 326, 329, 350 Menstruation, 295, 299, 326, 329 Mental, iv, 5, 54, 240, 242, 286, 287, 295, 298, 306, 317, 329, 346, 352, 361, 372 Mental Disorders, 317, 329, 346, 352 Mental Health, iv, 5, 240, 242, 329, 352 Mental Retardation, 54, 329 Mercury, 106, 330 Mesenchymal, 10, 14, 303, 330 Mesoderm, 20, 289, 330 Meta-Analysis, 122, 330 Metabolite, 267, 297, 303, 330, 353 Metallothionein, 187, 330 Metaphase, 279, 330 Metaplasia, 200, 330 Metastasis, 17, 53, 128, 169, 177, 285, 328, 330 Metastatic, 17, 51, 330, 360 Metastatic cancer, 17, 330 Methicillin Resistance, 106, 330 Methionine, 297, 330 Methotrexate, 248, 330 MI, 34, 55, 94, 103, 134, 147, 230, 265, 330 Mice Minute Virus, 330, 343 Microbe, 199, 330, 331, 367, 369 Microbiological, 127, 137, 331 Microbiology, 18, 134, 135, 149, 224, 228 Microcalcifications, 282, 331 Microfilaments, 321, 331 Microglia, 43, 190, 276, 331 Micronutrients, 228, 331 Microorganism, 289, 331, 343, 375 Microscopy, 51, 278, 331, 338 Microtubule-Associated Proteins, 331, 336 Microtubules, 321, 331, 336
390
Tetracycline
Middle Cerebral Artery, 184, 331 Mifepristone, 181, 331 Migration, 31, 37, 137, 166, 216, 289, 331, 344 Milliliter, 280, 331 Millimeter, 301, 331 Mineralization, 35, 282, 332, 340 Mineralocorticoids, 269, 293, 332 Minocycline, 5, 35, 43, 48, 49, 66, 69, 74, 77, 81, 85, 134, 135, 146, 160, 165, 166, 190, 199, 221, 227, 248 Miscible, 176, 332, 345 Mitochondria, 19, 117, 145, 332, 334, 339 Mitochondrial Swelling, 332, 335 Mitosis, 46, 275, 332 Mobility, 63, 106, 332 Mobilization, 145, 332 Mode of Transmission, 218, 332 Modeling, 299, 332 Modification, 46, 54, 85, 173, 195, 271, 310, 332 Modulator, 156, 203, 332 Molecular Probes, 300, 332 Molecule, 36, 37, 56, 59, 173, 181, 186, 187, 217, 270, 274, 277, 278, 283, 287, 289, 290, 294, 298, 300, 302, 304, 305, 309, 311, 312, 314, 316, 320, 332, 338, 341, 347, 352, 354, 355, 362, 366, 370, 374 Monitor, 45, 86, 101, 293, 332, 338 Monoclonal, 42, 178, 316, 317, 323, 332, 354, 376 Monoclonal antibodies, 178, 317, 332 Monocyte, 13, 110, 333 Monocytes, 150, 321, 324 Mononuclear, 313, 333, 371 Morphogenesis, 62, 71, 333 Morphological, 7, 43, 301, 308, 329, 333 Morphology, 55, 275, 284, 333 Motility, 52, 309, 319, 333, 361 Motion Sickness, 333, 335 Motor Neurons, 8, 49, 333 Mucins, 296, 312, 333, 359 Mucociliary, 333, 362 Mucocutaneous, 200, 333 Mucosa, 147, 228, 246, 309, 326, 333, 335, 350, 365, 366 Mucositis, 173, 210, 333, 368 Mucus, 179, 247, 280, 333 Multiple sclerosis, 190, 333 Muscle Contraction, 216, 300, 333, 360 Muscle Fibers, 333, 334 Muscular Dystrophies, 300, 333
Mustard Gas, 323, 333 Mutagenesis, 11, 17, 27, 85, 333 Mutagens, 308, 333 Mutate, 46, 334 Myalgia, 319, 334 Mycoplasma, 5, 75, 81, 82, 84, 98, 334 Mycosis, 334, 342 Mycotic, 214, 334 Myelin, 190, 333, 334 Myelogenous, 28, 58, 334 Myocardial infarction, 28, 34, 113, 198, 293, 330, 334, 350, 374, 375 Myocardial Ischemia, 34, 272, 334 Myocardial Reperfusion, 34, 334, 356 Myocardial Reperfusion Injury, 34, 334, 356 Myocarditis, 38, 334 Myocardium, 34, 38, 272, 330, 334 Myofibrils, 300, 334 Myosin, 77, 117, 333, 334 Myotonia, 334, 353 N Naevus, 130, 335 Naive, 9, 42, 58, 335 Naproxen, 208, 335 Nasal Cavity, 168, 169, 335, 342 Nasal Mucosa, 319, 335 Nasal Septum, 335 Nausea, 177, 274, 279, 298, 319, 335, 352, 372 NCI, 1, 113, 239, 288, 335 Necrosis, 34, 38, 176, 275, 281, 292, 319, 330, 334, 335, 356, 359 Neocortex, 335, 336 Neomycin, 45, 208, 335 Neonatal, 20, 312, 335 Neoplasia, 41, 58, 335 Neoplasm, 335, 342, 360, 372 Neoplastic, 41, 53, 63, 272, 316, 327, 335, 339 Nephritis, 13, 335 Nephron, 311, 335 Nephropathy, 324, 335 Nephrosis, 335 Nephrotic, 226, 335, 336 Nephrotic Syndrome, 226, 336 Nephrotoxic, 13, 198, 336 Nerve, 49 Nerve Degeneration, 49, 336 Nerve Growth Factor, 118, 336 Nervous System, 7, 36, 49, 183, 184, 190, 201, 267, 269, 278, 285, 288, 300, 308,
391
311, 313, 325, 328, 331, 333, 336, 337, 339, 344, 361, 366 Neural, 16, 21, 62, 184, 189, 221, 269, 272, 316, 331, 336 Neural Crest, 16, 62, 336 Neural Pathways, 336 Neuroblastoma, 99, 336 Neurodegenerative Diseases, 25, 222, 336 Neurofibrillary Tangles, 201, 336 Neurofilaments, 336 Neurologic, 12, 190, 201, 226, 336 Neuronal, 7, 12, 25, 43, 56, 288, 336, 344 Neuronal Plasticity, 56, 336 Neurons, 8, 13, 21, 25, 49, 201, 222, 296, 305, 308, 325, 333, 335, 336, 366, 367 Neurophysiology, 296, 336, 337 Neuroretinitis, 337, 357 Neurosciences, 26, 337 Neurotoxic, 43, 267, 337 Neurotoxicity, 43, 337 Neurotoxin, 25, 222, 337 Neurotransmitter, 267, 271, 281, 298, 311, 315, 322, 337, 338, 362, 366 Neutrons, 271, 323, 337, 354 Neutropenia, 226, 337 Neutrophil, 14, 154, 216, 337 Nevus, 120, 337 Niacinamide, 89, 117, 136, 155, 337 Nifedipine, 144, 337 Nitric Oxide, 38, 65, 76, 337 Nitrogen, 201, 270, 271, 272, 294, 305, 307, 337, 371 Nitrosamines, 337, 338 Nitrosation, 121, 338 Norepinephrine, 267, 269, 298, 337, 338, 357 Norfloxacin, 79, 338 Nosocomial, 43, 338 Nuclear, 7, 19, 37, 72, 97, 100, 101, 305, 308, 321, 335, 338, 358 Nuclei, 271, 310, 332, 337, 338, 339, 352, 359 Nucleic Acid Hybridization, 316, 338 Nucleocapsid, 203, 338 Nucleolus, 338, 358 Nutritional Status, 112, 338 O Ocular, 99, 179, 200, 205, 206, 252, 268, 335, 338 Odour, 275, 338, 372 Ointments, 209, 227, 298, 338
Omeprazole, 91, 100, 101, 120, 135, 136, 171, 338 Oncogene, 41, 69, 87, 146, 339 Oncogenic, 28, 41, 50, 320, 324, 339 Oncolysis, 339 Oncolytic, 15, 52, 88, 339 Oophoritis, 312, 339 Opacity, 284, 296, 339 Open Reading Frames, 324, 339 Operon, 60, 174, 339, 350, 356 Ophthalmic, 179, 339 Ophthalmology, 30, 62, 64, 99, 120, 307, 339 Opsin, 81, 125, 339, 357, 358 Optic Disk, 292, 297, 327, 339 Optic Nerve, 299, 337, 339, 341, 357, 360 Optic nerve head, 299, 337, 339 Oral Health, 226, 231, 339 Oral Hygiene, 313, 339 Organ Culture, 42, 339, 369 Organelles, 295, 329, 339 Ori region, 339, 356 Orofacial, 224, 340 Osmosis, 340 Osmotic, 52, 148, 270, 332, 340, 361 Ossification, 340, 358 Osteoarthritis, 5, 248, 340 Osteoblasts, 178, 340 Osteoclasts, 121, 340 Osteocytes, 35, 340 Osteogenesis, 101, 340 Osteogenic sarcoma, 340 Osteomalacia, 123, 340 Osteomyelitis, 103, 224, 340 Osteoporosis, 35, 92, 101, 248, 251, 340, 355 Osteosarcoma, 24, 340 Ototoxic, 198, 340 Outpatient, 108, 340 Ovarian Follicle, 19, 293, 313, 340 Ovaries, 40, 340, 361 Ovary, 80, 293, 304, 312, 339, 340, 341, 347 Overexpress, 44, 51, 52, 341 Ovum, 293, 295, 310, 325, 340, 341, 350 Oxazolidinones, 207, 341 Oxidants, 53, 104, 148, 341 Oxidation, 54, 152, 225, 267, 274, 294, 325, 341, 372 Oxidation-Reduction, 341 Oxidative Phosphorylation, 12, 267, 341 Oxidative Stress, 7, 8, 341
392
Tetracycline
P Pachymeningitis, 329, 341 Pactamycin, 195, 341 Paediatric, 255, 341 Palate, 226, 341, 365 Palladium, 205, 341 Palliative, 43, 341, 368 Palmitic Acid, 209, 341 Pancreas, 267, 279, 297, 320, 323, 325, 341, 342, 371 Pancreatic, 69, 146, 150, 182, 342 Pancreatitis, 158, 176, 342 Papilloma, 342, 358 Paracoccidioidomycosis, 214, 342 Paralysis, 37, 190, 342 Paranasal Sinuses, 342, 362 Parasite, 214, 215, 342, 371 Parasitic, 294, 342, 359 Parasitization, 272, 342 Parathyroid, 342, 359 Parathyroid Glands, 342, 359 Parenteral, 177, 342 Parietal, 339, 342, 344, 347 Parkinsonism, 222, 275, 325, 342 Paromomycin, 82, 195, 342 Partial remission, 342, 356 Particle, 21, 170, 203, 342, 370, 375 Parturition, 342, 350 Parvovirus, 95, 128, 330, 342 Patch, 227, 292, 343 Pathogen, 26, 48, 74, 86, 170, 193, 319, 343 Pathogenesis, 10, 12, 23, 34, 37, 38, 40, 42, 58, 59, 61, 80, 222, 227, 228, 343 Pathologic, 43, 222, 268, 275, 279, 282, 293, 316, 343, 352, 357 Pathologic Processes, 275, 343 Pathophysiology, 34, 44, 49, 53, 225, 343 Patient Education, 246, 260, 262, 265, 343 Patient Selection, 247, 343 Pediatric Dentistry, 136, 226, 343 Pelvic, 249, 254, 343, 351 Pelvic inflammatory disease, 249, 254, 343 Pelvis, 267, 340, 343, 373 Pemphigus, 23, 87, 117, 267, 343 Penicillin, 39, 47, 68, 72, 74, 80, 108, 109, 123, 224, 271, 330, 343 Penicillin Resistance, 48, 343 Penicillinase, 109, 343 Pepsin, 343 Peptic, 120, 136, 158, 228, 254, 343, 360, 366 Peptic Ulcer, 120, 136, 158, 228, 343, 360
Peptic Ulcer Hemorrhage, 343, 360 Peptide, 15, 172, 204, 212 Peptide Chain Elongation, 288, 343 Perception, 291, 343 Percutaneous, 106, 116, 343 Perfusion, 38, 279, 344, 369 Pericoronitis, 224, 344 Perineum, 344, 364 Periodontal disease, 4, 26, 94, 96, 134, 168, 183, 219, 227, 344 Periodontal Ligament, 110, 344 Periodontal Pocket, 4, 71, 91, 120, 344 Periodontitis, 4, 5, 95, 96, 99, 103, 117, 122, 123, 127, 128, 168, 219, 231, 311, 344 Perioral, 227, 249, 344 Peripheral Nerves, 184, 344, 364 Peripheral Nervous System, 336, 337, 344, 366 Peritoneal, 110, 192, 344 Peritoneal Cavity, 344 Peritoneal Dialysis, 110, 344 Peritoneum, 344 Peritonitis, 312, 344 Perivascular, 331, 344 Peroxide, 8, 102, 107, 344 PH, 65, 66, 280, 344 Phagocyte, 341, 345 Phagocytosis, 45, 331, 345 Phallic, 307, 345 Pharmaceutical Preparations, 208, 209, 285, 309, 345 Pharmaceutical Solutions, 298, 345 Pharmacokinetics, 299, 345 Pharmacologic, 34, 277, 293, 313, 345, 369 Pharyngitis, 251, 345 Pharynx, 319, 335, 345 Phenotype, 9, 16, 18, 20, 22, 23, 26, 28, 38, 41, 54, 57, 58, 59, 61, 62, 186, 206, 217 Phenyl, 209, 222, 267, 345 Phenylalanine, 345, 372 Phorbol, 18, 345 Phorbol Esters, 18, 345 Phosphates, 210, 345 Phosphodiesterase, 12, 345 Phospholipases, 345, 362 Phospholipids, 83, 176, 225, 306, 325, 329, 345 Phosphorus, 282, 342, 345, 346 Phosphorylated, 32, 289, 345 Phosphorylating, 51, 345 Phosphorylation, 12, 32, 46, 51, 346, 372 Phosphotyrosine, 51, 346
393
Photophobia, 200, 346 Photoreceptor, 30, 55, 346, 358 Photosensitization, 121, 346 Phylogeny, 78, 346 Physiologic, 38, 270, 279, 298, 313, 317, 329, 331, 346, 355, 357, 371 Physiology, 9, 52, 53, 89, 137, 145, 157, 186, 337, 346, 374 Pigment, 30, 95, 167, 278, 329, 346, 357 Pigmentation, 335, 346 Pituitary Gland, 293, 306, 346 Placenta, 134, 225, 304, 346, 350 Plague, 246, 254, 346 Plant Oils, 338, 346 Plants, 135, 173, 208 Plaque, 121, 231, 273, 287, 346 Plasma cells, 273, 346 Plasma protein, 270, 302, 346, 361 Plasmid, 21, 26, 66, 68, 69, 73, 78, 80, 83, 84, 134, 172, 182, 192, 196 Plasticity, 6, 56, 347 Platelet Activation, 347, 362 Platelet Aggregation, 272, 337, 347, 368 Platelets, 145, 337, 347, 368 Platinum, 326, 341, 347 Pleura, 121, 347 Pleural, 92, 113, 314, 347, 368 Pleural cavity, 314, 347 Pleural Effusion, 92, 113, 347, 368 Pleurodesis, 90, 116, 121, 230, 347 Pneumonia, 79, 114, 168, 219, 252, 254, 292, 347, 371 Pneumothorax, 90, 116, 347, 368 Point Mutation, 37, 46, 67, 347 Poisoning, 226, 282, 286, 307, 330, 335, 347, 361 Pollen, 168, 347, 353 Polyarthritis, 323, 347, 362 Polycystic, 22, 42, 347 Polyethylene, 176, 348 Polymerase, 182, 186, 187, 310, 348, 350, 356 Polymerase Chain Reaction, 182, 348 Polymorphic, 10, 54, 287, 348 Polypeptide, 174, 186, 187, 212, 217, 268, 271, 289, 303, 306, 316, 348, 350, 351, 376 Polyposis, 63, 348 Polyproteins, 309, 348 Polysaccharide, 274, 285, 311, 348, 352 Population Dynamics, 42, 348 Porphyria, 121, 226, 348 Porphyrins, 348
Posterior, 123, 272, 276, 287, 298, 321, 322, 341, 348, 360 Postmenopausal, 35, 92, 251, 340, 348, 355 Postnatal, 348, 364 Postoperative, 102, 348 Postoperative Period, 102, 348 Postsynaptic, 348, 362 Post-translational, 53, 194, 349 Potassium, 7, 83, 140, 179, 332, 349 Potentiate, 9, 349 Potentiation, 349, 362 Practice Guidelines, 242, 249, 349 Precancerous, 286, 349 Precipitating Factors, 284, 349 Preclinical, 52, 349 Precursor, 20, 203, 204 Predisposition, 167, 248, 349 Prednisolone, 248, 349 Prednisone, 248, 349 Prenatal, 301, 349 Prevalence, 67, 122, 349 Prickle, 267, 323, 349 Prion, 84, 230, 349 Probe, 7, 11, 128, 150, 349 Procaine, 325, 350 Procollagen, 14, 350 Proctocolitis, 255, 350 Progeny, 21, 350 Progesterone, 134, 181, 331, 350, 364 Progression, 14, 17, 21, 22, 29, 32, 33, 34, 40, 46, 49, 50, 55, 57, 61, 180, 230, 273, 350, 371 Projection, 25, 295, 338, 339, 350 Prolactin, 49, 350 Proline, 289, 316, 350 Promotor, 29, 34, 350, 357 Prophase, 279, 350, 367 Prophylaxis, 209, 224, 252, 350, 358, 373, 375 Proportional, 309, 350 Propranolol, 202, 350 Prospective Studies, 179, 350 Prospective study, 120, 350 Prostaglandins, 275, 300, 319, 331, 351 Prostaglandins A, 319, 351 Prostaglandins F, 331, 351 Prostate, 17, 40, 57, 87, 279, 351, 371 Prostatitis, 250, 351 Protease, 290, 309, 351 Protective Agents, 221, 351 Protein Binding, 51, 351, 369
394
Tetracycline
Protein C, 11, 23, 186, 187, 206, 217, 270, 271, 275, 277, 323, 325, 351, 363, 372, 375 Protein Conformation, 271, 323, 351 Protein Folding, 8, 351 Protein Kinases, 7, 351 Proteinuria, 336, 351 Proteoglycan, 62, 352 Proteolytic, 14, 112, 169, 290, 303, 306, 352 Protocol, 42, 352 Proton Pump, 247, 339, 352 Protons, 271, 316, 322, 352, 354 Proto-Oncogenes, 19, 41, 352 Protozoa, 279, 331, 352, 364 Protozoan, 294, 310, 327, 352, 371 Provirus, 170, 175, 193, 352 Proximal, 38, 62, 110, 176, 298, 324, 335, 352 Pruritic, 352, 369 Psittacosis, 165, 205, 352 Psoriasis, 166, 176, 218, 333, 352, 358 Psychiatry, 307, 352, 374 Psychic, 325, 329, 352 Public Health, 10, 64, 123, 242, 254, 352 Public Policy, 241, 353 Publishing, 65, 166, 216, 224, 225, 227, 353 Pulmonary, 16, 51, 59, 252, 253, 280, 281, 291, 292, 325, 353, 366, 374, 375 Pulmonary Artery, 59, 280, 353, 374 Pulmonary Embolism, 353, 375 Pulmonary hypertension, 59, 292, 353 Pulse, 201, 332, 353 Pupil, 292, 353 Purines, 277, 353, 361, 376 Purulent, 312, 353, 373 Pustular, 268, 315, 353 Pyogenic, 340, 353 Pyrimidines, 277, 353, 361 Q Quaternary, 351, 353 Quercetin, 144, 353 Quinine, 10, 111, 123, 134, 135, 288, 353 Quinolinic, 98, 353 Quinolinic Acid, 98, 353 Quinolones, 81, 82, 353 R Race, 202, 218, 298, 331, 354 Radiation, 33, 40, 56, 174, 177, 214, 226 Radiation therapy, 33, 305, 321, 323, 354, 376 Radioactive, 45, 280, 313, 316, 318, 321, 323, 332, 333, 338, 339, 354, 371, 376 Radioimmunotherapy, 354
Radioisotope, 354 Radioisotope Renography, 354 Radiolabeled, 280, 323, 354, 376 Radiological, 101, 137, 344, 354 Radiology, 102, 129, 354 Radionuclide Angiography, 61, 354 Radionuclide Imaging, 102, 354 Radiotherapy, 174, 177, 210, 214, 281, 323, 354, 376 Radius, 35, 354 Raloxifene, 354, 360 Random Allocation, 355 Randomization, 48, 355 Randomized, 48, 49, 64, 80, 91, 113, 120, 174, 300, 355 Ranitidine, 3, 111, 120, 135, 247, 355 Ranitidine Bismuth Citrate, 3, 111, 120, 135, 247, 355 Reactive Oxygen Species, 12, 18, 53, 89, 355 Reagent, 37, 307, 316, 355 Receptors, Antigen, 290, 355 Recombinant, 15, 22, 53, 55, 60, 71, 76, 83, 128, 175, 182, 185, 203, 279, 355, 374 Recombination, 58, 66, 187, 310, 355 Reconstitution, 23, 53, 355 Rectum, 275, 280, 290, 297, 308, 319, 324, 350, 351, 355, 366 Recurrence, 64, 249, 355 Red blood cells, 272, 304, 355, 359 Reductase, 330, 355 Refer, 1, 170, 193, 281, 290, 307, 308, 314, 315, 326, 327, 335, 337, 338, 354, 355, 370, 374 Reflux, 355, 366 Refraction, 355, 363 Regeneration, 20, 36, 306, 355, 356 Regimen, 4, 33, 122, 300, 356 Reinfection, 167, 356 Relapse, 41, 356 Remission, 126, 355, 356 Renal cysts, 22, 356 Renal failure, 23, 42, 356 Renin, 61, 273, 283, 356 Renin-Angiotensin System, 283, 356 Reperfusion, 28, 34, 334, 356 Reperfusion Injury, 28, 34, 356 Replication Origin, 19, 67, 173, 356 Replicon, 26, 211, 356 Repressor Proteins, 181, 185, 206, 356 Resection, 247, 357, 362 Reserpine, 156, 357
395
Resorption, 340, 357 Respiration, 283, 332, 357 Respiratory distress syndrome, 281, 357 Response Elements, 15, 85, 357 Restitution, 14, 52, 357 Restoration, 29, 31, 57, 334, 355, 356, 357, 375 Retina, 30, 31, 55, 167, 188, 287, 292, 297, 299, 301, 324, 327, 337, 339, 357, 358, 359, 375 Retinae, 327, 357 Retinal, 30, 31, 55, 167, 291, 297, 339, 357, 358 Retinal pigment epithelium, 167, 357 Retinitis, 188, 357, 358 Retinoblastoma, 15, 39, 51, 357 Retinoblastoma Protein, 15, 357 Retinoids, 18, 358 Retinol, 357, 358 Retinopathy, 31, 166, 297, 358 Retrograde, 322, 358 Retroviral vector, 6, 20, 50, 77, 80, 105, 119, 173, 174, 175, 203, 310, 358 Retrovirus, 21, 51, 65, 75, 203, 358 Reversion, 358, 372 Rheumatism, 102, 317, 358 Rheumatoid, 5, 168, 176, 183, 248, 287, 335, 341, 358 Rheumatoid arthritis, 5, 168, 176, 183, 248, 287, 335, 358 Rhinophyma, 247, 268, 358 Rhodopsin, 81, 125, 339, 357, 358 Ribonuclease, 15, 358 Ribonucleoside Diphosphate Reductase, 316, 358 Ribosome, 45, 72, 77, 161, 195, 358, 370 Rickets, 226, 358 Rickettsia, 211, 359 Rickettsiae, 165, 205, 211, 359 Rigidity, 39, 342, 346, 359 Risk factor, 64, 167, 284, 350, 359 Rod, 277, 302, 346, 359 Rolitetracycline, 208, 359 Root Planing, 4, 231, 359 Roxithromycin, 202, 359 Rubella, 226, 359 Rutin, 353, 359 S Saliva, 210, 359 Salivary, 168, 294, 296, 297, 359, 362, 366 Salivary glands, 294, 296, 297, 359, 362 Salpingitis, 108, 312, 359
Saponins, 359, 365 Sarcoid, 228, 359 Sarcoidosis, 359 Sarcolemma, 334, 360 Sarcoma, 9, 73, 106, 360 Sarcoplasmic Reticulum, 151, 360 Saturated fat, 341, 360 Sclera, 287, 291, 292, 360 Sclerosis, 8, 12, 49, 190, 201, 333, 360 Sclerotherapy, 90, 113, 114, 360 Screening, 35, 47, 80, 128, 165, 173, 191, 194, 195, 206, 289, 360 Sebaceous, 220, 323, 328, 329, 358, 360 Sebaceous gland, 220, 323, 328, 329, 358, 360 Sebum, 268, 360 Secondary tumor, 330, 360 Secretory, 339, 360 Segregation, 355, 360 Selective estrogen receptor modulator, 248, 354, 360 Semen, 351, 360 Seminiferous tubule, 320, 360 Semisynthetic, 74, 271, 284, 288, 289, 317, 332, 359, 360 Senescence, 56, 361 Senile, 340, 361 Sensor, 7, 42, 120, 361 Sepsis, 38, 176, 361 Septic, 38, 44, 104, 148, 176, 276, 361 Septicemia, 174, 361 Sequence Analysis, 78, 361 Sequence Homology, 53, 361 Sequencing, 26, 61, 348, 361 Serine, 46, 268, 361, 371 Serotonin, 274, 337, 357, 361, 371 Serous, 302, 347, 361 Serum, 13, 34, 67, 143, 145, 148, 156, 213 Serum Albumin, 145, 148, 361 Sex Characteristics, 272, 361 Sexual Partners, 249, 361 Sexually Transmitted Diseases, 5, 96, 108, 123, 249, 361 Shame, 280, 361 Shedding, 220, 226, 361 Shigellosis, 108, 361 Shock, 38, 44, 79, 104, 148, 176, 185, 186, 217, 221, 302, 361, 371 Short Bowel Syndrome, 251, 362 Shyness, 172, 362 Sicca, 83, 362
396
Tetracycline
Signal Transduction, 6, 37, 53, 57, 59, 194, 346, 362 Signs and Symptoms, 356, 362, 372 Single-agent, 10, 362 Sinusitis, 168, 219, 362 Skeletal, 272, 296, 323, 333, 334, 360, 362 Skeleton, 268, 306, 323, 362 Skull, 362, 367 Small intestine, 144, 288, 299, 303, 310, 315, 317, 322, 362, 371, 374 Smallpox, 18, 255, 362, 373 Smooth muscle, 34, 216, 272, 276, 291, 315, 351, 356, 362, 366 Sneezing, 361, 362 Sodium, 147, 148, 152, 179, 200, 203, 312, 332, 335, 353, 362, 363 Sodium Dodecyl Sulfate, 200, 363 Sodium Fluoride, 148, 152, 363 Soft tissue, 196, 197, 198, 200, 226, 280, 362, 363 Solid tumor, 177, 273, 280, 299, 363 Solvent, 176, 177, 278, 297, 311, 340, 345, 363 Soma, 363 Somatic, 181, 301, 316, 329, 332, 344, 363 Somatic cells, 329, 332, 363 Soybean Oil, 135, 363 Specialist, 256, 363 Species Specificity, 32, 363 Specificity, 11, 15, 26, 27, 32, 36, 40, 52, 77, 208, 270, 282, 363, 369 Spectinomycin, 74, 80, 195, 363 Spectrin, 300, 363 Spectrophotometry, 145, 363 Spectrum, 165, 167, 168, 183, 192, 198, 205, 206, 219, 224, 317, 331, 338, 359, 363 Sperm, 249, 272, 287, 347, 360, 364 Sphincter, 324, 364 Spinal cord, 14, 36, 49, 184, 276, 281, 285, 287, 299, 308, 329, 336, 341, 344, 364 Spinal Nerves, 344, 364 Spinous, 303, 323, 364 Spiramycin, 99, 364 Spirochete, 364, 367 Spleen, 192, 294, 326, 360, 364 Spondylitis, 248, 364 Sporadic, 336, 357, 364 Spores, 289, 364 Sprue, 246, 251, 364 Sputum, 94, 364 Stabilization, 37, 83, 364
Staphylococcus, 67, 72, 73, 76, 78, 85, 95, 106, 118, 124, 125, 145, 156, 211, 332, 364 Staphylococcus aureus, 67, 72, 76, 85, 95, 106, 118, 124, 125, 145, 156, 211, 364 Steatosis, 225, 306, 364 Stem Cells, 13, 21, 27, 364 Stent, 202, 364 Sterile, 155, 169, 201, 276, 342, 364 Sterility, 294, 364 Steroid, 93, 105, 174, 181, 186, 217, 278, 293, 359, 364 Stimulant, 315, 365 Stimulus, 150, 186, 203, 217, 299, 300, 305, 322, 365, 368 Stoma, 365, 368 Stomatitis, 21, 73, 105, 203, 365 Stool, 290, 324, 365 Strand, 19, 348, 365 Streptococcal, 71, 74, 78, 80, 84, 104, 148, 325, 365 Streptococci, 70, 365 Streptococcus, 68, 73, 74, 76, 78, 80, 85, 97, 108, 116, 118, 121, 122, 365 Streptomycin, 68, 108, 161, 195, 208, 365 Stress, 7, 8, 18, 46, 49, 52, 53, 149, 247, 284, 293, 307, 335, 341, 349, 358, 365, 373 Striatum, 21, 25, 365 Stroke, 12, 184, 198, 203, 240, 323, 365 Stroma, 31, 62, 322, 365 Stromal, 17, 31, 365 Subacute, 319, 327, 362, 365 Subarachnoid, 184, 313, 346, 365 Subclinical, 156, 319, 365 Subcutaneous, 52, 269, 285, 300, 342, 365 Submaxillary, 303, 366 Subspecies, 363, 366, 373 Substance P, 280, 304, 330, 355, 360, 365, 366 Substrate, 24, 39, 53, 72, 77, 188, 287, 303, 356, 366 Substrate Specificity, 77, 366 Sucralfate, 174, 366 Sulfates, 196, 197, 199, 209, 363, 366 Sulfuric acid, 209, 366 Sunburn, 158, 247, 366, 372 Superoxide, 7, 8, 366 Superoxide Dismutase, 7, 8, 366 Suppositories, 309, 366 Suppression, 63, 81, 84, 154, 293, 366 Suppressive, 43, 63, 366 Surfactant, 154, 363, 366 Sympathomimetic, 298, 303, 338, 366
397
Symphysis, 286, 351, 366 Symptomatic, 114, 180, 342, 366 Symptomatology, 167, 366 Synapse, 269, 366, 367, 370 Synapsis, 367 Synaptic, 6, 337, 362, 367 Synergistic, 25, 126, 169, 188, 211, 350, 367, 369 Synovial, 5, 137, 155, 367 Syphilis, 250, 367 Systemic disease, 22, 26, 361, 367 Systemic lupus erythematosus, 287, 367 Systemic therapy, 287, 367 Systolic, 316, 367 T Tacrolimus, 93, 367 Talc, 90, 367 Talcum, 201, 367 Talcum powder, 201, 367 Tear Gases, 323, 367 Teichoic Acids, 313, 367 Telangiectasia, 219, 220, 367 Temporal, 7, 18, 19, 30, 40, 56, 62, 82, 118, 315, 327, 367 Testicular, 40, 367 Testis, 40, 304, 367 Therapeutics, 3, 32, 43, 99, 100, 120, 122, 235, 368 Thermal, 38, 298, 337, 348, 368 Thigh, 306, 368 Thoracic, 116, 121, 297, 347, 368, 375 Thoracostomy, 255, 368 Threonine, 56, 361, 368 Threshold, 9, 54, 305, 316, 368 Thrombin, 306, 347, 351, 368 Thrombocytes, 347, 368 Thrombomodulin, 351, 368 Thrombosis, 184, 320, 351, 360, 365, 368 Thromboxanes, 275, 300, 368 Thrombus, 293, 319, 323, 334, 347, 368, 374 Thrush, 282, 368 Thymidine, 172, 368 Thymidine Kinase, 172, 368 Thymus, 317, 326, 368 Thyroid, 112, 312, 316, 342, 368, 369, 372 Thyroid Gland, 312, 316, 342, 368, 369 Thyroid Nodule, 112, 368 Thyroxine, 270, 345, 369 Tic, 48, 369 Tinea Pedis, 214, 369 Tinidazole, 120, 369 Tissue Culture, 181, 218, 369
Tissue Distribution, 282, 369 Titre, 203, 369 Tolerance, 9, 11, 268, 311, 369 Tomography, 280, 369 Tone, 339, 369 Tonic, 50, 369 Tooth Preparation, 269, 369 Topical, 42, 64, 96, 100, 113, 120, 129, 130, 134, 179, 183, 184, 200, 209, 227, 228, 234, 247, 249, 276, 287, 297, 316, 369 Torsion, 319, 369 Toxicity, 8, 30, 46, 49, 52, 148, 171, 172, 199, 209, 230, 299, 330, 366, 369 Toxicology, 101, 223, 242, 369 Toxin, 192, 302, 369, 370 Toxoplasmosis, 277, 370 Trachea, 281, 324, 345, 368, 370 Trachoma, 64, 100, 120, 370 Transcriptase, 175, 309, 358, 370 Transcription Factors, 10, 12, 13, 24, 32, 58, 62, 181, 357, 370 Transduction, 6, 37, 53, 57, 59, 194, 362, 370 Transfection, 13, 16, 17, 24, 37, 51, 54, 170, 172, 279, 301, 310, 370 Transfer Factor, 317, 370 Transferases, 312, 370 Transforming Growth Factor beta, 40, 370 Transgenes, 7, 13, 61, 88, 187, 370 Translating, 54, 370 Translation, 54, 69, 172, 181, 207, 271, 304, 335, 370 Translational, 9, 27, 53, 195, 370 Translocation, 38, 58, 100, 288, 304, 370 Transmitter, 267, 276, 298, 322, 328, 338, 370 Transplantation, 22, 174, 210, 251, 288, 317, 327, 370 Transposons, 204, 371 Trauma, 7, 12, 38, 102, 103, 130, 184, 218, 226, 248, 254, 255, 304, 313, 335, 342, 371, 375 Treatment Failure, 4, 47, 371 Tremor, 342, 371 Trichomoniasis, 330, 371 Tricuspid Atresia, 292, 371 Triglyceride, 219, 371 Trimethoprim-sulfamethoxazole, 72, 108, 371 Trophic, 336, 371 Tropism, 15, 371 Trypsin, 75, 112, 303, 371
398
Tetracycline
Tryptophan, 289, 353, 361, 371 Tumor marker, 279, 371 Tumor model, 27, 126, 371 Tumor Necrosis Factor, 38, 371 Tumor suppressor gene, 39, 63, 357, 371 Tumorigenic, 41, 371 Tumour, 308, 339, 372 Tunica, 302, 333, 372 Typhimurium, 191, 372 Tyrosine, 8, 21, 25, 51, 267, 298, 346, 372 U Ubiquitin, 336, 372 Ulcer, 14, 135, 136, 144, 158, 228, 247, 254, 285, 299, 343, 366, 372, 373 Ulceration, 98, 343, 372 Ulna, 35, 372 Ultraviolet radiation, 366, 372 Unconscious, 295, 317, 372 Uncoupling Agents, 322, 372 Uracil, 353, 372, 373 Uraemia, 342, 372 Urea, 4, 372 Urea Breath Test, 4, 372 Urease, 372 Uremia, 356, 372 Ureters, 372, 373 Urethra, 351, 373 Urethritis, 100, 250, 252, 253, 312, 373 Uric, 270, 312, 353, 373 Uridine Diphosphate, 100, 373 Urinary, 69, 99, 284, 288, 294, 310, 338, 372, 373, 375 Urinary tract, 69, 284, 373 Urinary tract infection, 69, 373 Urine, 279, 293, 303, 338, 351, 372, 373 Urogenital, 83, 98, 105, 310, 312, 373 Urticaria, 98, 373 Uterus, 267, 286, 293, 295, 302, 329, 340, 350, 373 V Vaccination, 18, 170, 192, 193, 255, 373 Vaccine, 18, 169, 170, 192, 193, 214, 228, 248, 255, 269, 352, 373 Vaccinia, 18, 60, 71, 373 Vaccinia Virus, 18, 71, 373 Vacuoles, 302, 339, 373 Vagina, 282, 286, 296, 329, 373 Vaginal, 373 Vaginitis, 225, 282, 373 Vaginosis, 69, 373 Varicose, 360, 373 Varicose vein, 360, 373
Variola, 373 Vascular, 13, 35, 38, 51, 59, 216, 287, 302, 319, 337, 340, 346, 368, 373, 374 Vascular endothelial growth factor, 59, 374 Vasculitis, 342, 374 Vasodilator, 281, 298, 315, 334, 337, 374 VE, 42, 51, 374 Vein, 202, 272, 322, 338, 374 Venereal, 136, 367, 374 Venous, 281, 314, 351, 371, 374, 375 Venous Thrombosis, 374, 375 Ventilation, 281, 374 Ventricle, 61, 276, 292, 315, 353, 367, 371, 374 Ventricular, 16, 34, 61, 292, 334, 371, 374 Ventricular Remodeling, 34, 374 Venules, 280, 282, 302, 374 Vertebrae, 321, 364, 374 Vesicular, 21, 73, 105, 203, 313, 315, 362, 373, 374 Vestibular, 313, 374 Veterinary Medicine, 196, 197, 198, 199, 209, 241, 374 Vibrio, 73, 74, 94, 100, 126, 130, 287, 374 Vibrio cholerae, 94, 100, 126, 130, 287, 374 Villous, 284, 374 Villus, 52, 374 Viral Proteins, 26, 170, 374 Viral vector, 20, 25, 60, 203, 374 Virion, 21, 175, 186, 187, 277, 338, 375 Virulence, 26, 44, 170, 191, 228, 276, 369, 375 Virulent, 170, 193, 375 Virus Replication, 43, 60, 375 Viscosity, 177, 375 Vital Capacity, 49, 375 Vitreous, 188, 287, 297, 324, 357, 375 Vitreous Body, 287, 357, 375 Vitreous Hemorrhage, 297, 375 Vitro, 8, 13, 15, 18, 19, 23, 25, 27, 30, 32, 36, 38, 43, 50, 51, 53, 55, 57, 59, 62, 67, 69, 72, 74, 75, 82, 135, 136, 149, 150, 155, 156, 157, 165, 166, 185, 192, 205 Vivo, 8, 10, 13, 14, 15, 18, 21, 25, 29, 30, 32, 33, 36, 38, 41, 42, 43, 44, 50, 52, 53, 54, 55, 57, 59, 60, 63, 72, 74, 82, 155, 173, 185, 193, 196, 228 Vulnerary, 146, 375 W Warfarin, 171, 375
399
White blood cell, 268, 273, 324, 326, 327, 333, 337, 346, 375 Windpipe, 345, 368, 375 Wound Healing, 31, 63, 166, 285, 306, 320, 328, 375 Wound Infection, 224, 375 X Xanthine, 270, 375, 376 Xanthine Oxidase, 270, 376
Xenobiotics, 53, 376 Xenograft, 29, 273, 371, 376 X-ray, 11, 32, 131, 195, 280, 284, 292, 307, 308, 323, 328, 338, 354, 376 X-ray therapy, 323, 376 Y Yeasts, 282, 308, 321, 345, 376 Z Zymogen, 351, 376
400
Tetracycline
