DOXYCYCLINE A M EDICAL D ICTIONARY , B IBLIOGRAPHY , AND A NNOTATED R ESEARCH G UIDE TO I NTERNET R E FERENCES
J AMES N. P ARKER , M.D. AND P HILIP M. P ARKER , P H .D., E DITORS
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ICON Health Publications ICON Group International, Inc. 4370 La Jolla Village Drive, 4th Floor San Diego, CA 92122 USA Copyright 2003 by ICON Group International, Inc. Copyright 2003 by ICON Group International, Inc. All rights reserved. This book is protected by copyright. No part of it may be reproduced, stored in a retrieval system, or transmitted in any form or by any means, electronic, mechanical, photocopying, recording, or otherwise, without written permission from the publisher. Printed in the United States of America. Last digit indicates print number: 10 9 8 7 6 4 5 3 2 1
Publisher, Health Care: Philip Parker, Ph.D. Editor(s): James Parker, M.D., Philip Parker, Ph.D. Publisher's note: The ideas, procedures, and suggestions contained in this book are not intended for the diagnosis or treatment of a health problem. As new medical or scientific information becomes available from academic and clinical research, recommended treatments and drug therapies may undergo changes. The authors, editors, and publisher have attempted to make the information in this book up to date and accurate in accord with accepted standards at the time of publication. The authors, editors, and publisher are not responsible for errors or omissions or for consequences from application of the book, and make no warranty, expressed or implied, in regard to the contents of this book. Any practice described in this book should be applied by the reader in accordance with professional standards of care used in regard to the unique circumstances that may apply in each situation. The reader is advised to always check product information (package inserts) for changes and new information regarding dosage and contraindications before prescribing any drug or pharmacological product. Caution is especially urged when using new or infrequently ordered drugs, herbal remedies, vitamins and supplements, alternative therapies, complementary therapies and medicines, and integrative medical treatments. Cataloging-in-Publication Data Parker, James N., 1961Parker, Philip M., 1960Doxycycline: 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: 0-597-83894-1 1. Doxycycline-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 doxycycline. 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 DOXYCYCLINE........................................................................................... 3 Overview........................................................................................................................................ 3 The Combined Health Information Database................................................................................. 3 Federally Funded Research on Doxycycline .................................................................................. 5 E-Journals: PubMed Central ....................................................................................................... 61 The National Library of Medicine: PubMed ................................................................................ 64 CHAPTER 2. NUTRITION AND DOXYCYCLINE ............................................................................... 105 Overview.................................................................................................................................... 105 Finding Nutrition Studies on Doxycycline ............................................................................... 105 Federal Resources on Nutrition ................................................................................................. 108 Additional Web Resources ......................................................................................................... 109 CHAPTER 3. ALTERNATIVE MEDICINE AND DOXYCYCLINE ........................................................ 111 Overview.................................................................................................................................... 111 National Center for Complementary and Alternative Medicine................................................ 111 Additional Web Resources ......................................................................................................... 116 General References ..................................................................................................................... 117 CHAPTER 4. CLINICAL TRIALS AND DOXYCYCLINE ..................................................................... 119 Overview.................................................................................................................................... 119 Recent Trials on Doxycycline .................................................................................................... 119 Keeping Current on Clinical Trials ........................................................................................... 121 CHAPTER 5. PATENTS ON DOXYCYCLINE ..................................................................................... 123 Overview.................................................................................................................................... 123 Patents on Doxycycline ............................................................................................................. 123 Patent Applications on Doxycycline.......................................................................................... 134 Keeping Current ........................................................................................................................ 140 CHAPTER 6. BOOKS ON DOXYCYCLINE ......................................................................................... 141 Overview.................................................................................................................................... 141 The National Library of Medicine Book Index ........................................................................... 141 Chapters on Doxycycline ........................................................................................................... 142 CHAPTER 7. MULTIMEDIA ON DOXYCYCLINE .............................................................................. 145 Overview.................................................................................................................................... 145 Bibliography: Multimedia on Doxycycline ................................................................................ 145 CHAPTER 8. PERIODICALS AND NEWS ON DOXYCYCLINE ........................................................... 147 Overview.................................................................................................................................... 147 News Services and Press Releases.............................................................................................. 147 Academic Periodicals covering Doxycycline.............................................................................. 150 CHAPTER 9. RESEARCHING MEDICATIONS .................................................................................. 151 Overview.................................................................................................................................... 151 U.S. Pharmacopeia..................................................................................................................... 151 Commercial Databases ............................................................................................................... 152 APPENDIX A. PHYSICIAN RESOURCES .......................................................................................... 155 Overview.................................................................................................................................... 155 NIH Guidelines.......................................................................................................................... 155 NIH Databases........................................................................................................................... 157 Other Commercial Databases..................................................................................................... 160 APPENDIX B. PATIENT RESOURCES ............................................................................................... 161 Overview.................................................................................................................................... 161 Patient Guideline Sources.......................................................................................................... 161 Finding Associations.................................................................................................................. 165 APPENDIX C. FINDING MEDICAL LIBRARIES ................................................................................ 167
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Overview.................................................................................................................................... 167 Preparation................................................................................................................................. 167 Finding a Local Medical Library................................................................................................ 167 Medical Libraries in the U.S. and Canada ................................................................................. 167 ONLINE GLOSSARIES................................................................................................................ 173 Online Dictionary Directories ................................................................................................... 173 DOXYCYCLINE DICTIONARY ................................................................................................. 175 INDEX .............................................................................................................................................. 261
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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 doxycycline 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 doxycycline, 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 doxycycline, 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 doxycycline. 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 doxycycline, 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 doxycycline. 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 DOXYCYCLINE Overview In this chapter, we will show you how to locate peer-reviewed references and studies on doxycycline.
The Combined Health Information Database The Combined Health Information Database summarizes studies across numerous federal agencies. To limit your investigation to research studies and doxycycline, 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 “doxycycline” (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: •
Esophageal Ulceration Following Doxycycline Ingestion Source: Postgraduate Medicine. 91(1): 179-181. January 1992. Summary: Many reports in the medical literature have linked esophageal ulceration with ingestion of doxycycline capsules and tablets. This article describes for the first time a case of doxycycline-induced esophageal ulceration in which polarizable matrix material from the capsule was identified in biopsy specimens from the ulcer bed. Topics covered include biopsy investigation, the history of esophageal ulceration caused by ingestion of capsules and tablets, the mechanism by which doxycycline induces esophageal ulceration, the use of endoscopy for diagnosis, and treatment options. 2 figures. 10 references. (AA-M).
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Doxycycline
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Adjunctive Benefits of Subantimicrobial Dose Doxycycline in the Management of Severe, Generalized, Chronic Periodontitis Source: Journal of Periodontology. 73(7): 762-769. July 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: Severe, generalized periodontitis is a form of chronic periodontitis that appears to be associated with an exaggerated host response. Little information is available on the benefits of using adjunctive host modulation in the management of this form of periodontal disease. This article reports on a study of 30 subjects (less than 45 years of age) with severe, generalized periodontitis who received subgingival (under the gums) debridement and oral hygiene instructions each week for 4 weeks, plus 6 months of adjunctive subantimicrobial doxycycline (SDD) or placebo. Maintenance therapy was performed at 3, 5.25, and 8.25 months for both groups. Ten subjects in each group completed all phases of the study. Subgingival debridement plus adjunctive SDD reduced deep pockets by an average of 3.02 millimeters after 9 months versus 1.42 millimeters for the placebo group. A significant clinical response was seen in both groups as soon as 1 month, but the response was always clinically and statistically greater in the SDD group. 7 figures. 2 tables. 19 references.
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Utility of Subantimicrobial Dose Doxycycline: Statistical Versus Clinical Significance Source: Journal of Practical Hygiene. 11(5): 17,19-23. September-October 2002. Contact: Available from Montage Media Corporation. 1000 Wyckoff Avenue, Mahwah, NJ 07430-3164. (201) 891-3200. Summary: This article addresses modulation of the host response as it applies to periodontal therapy. Data from a phase III clinical trial indicated that root planing plus adjunctive use of subantimicrobial dose doxycycline (SDD) resulted in a statistically significant improvement when compared to root planing alone, with regard to: decreased prevalence of bleeding on probing (BOP) in shallow probing depths; reduction of probing depths; gains of clinical attachment; and decreased incidence of disease progression at deep probing depths. Therapists should consider if results attained beyond root planing are clinically relevant. Accordingly, the author discusses statistical versus clinical significance as it applies to the adjunctive use of SDD. Furthermore, the author suggests that since periodontitis is an infectious disease, the main objective of periodontal therapy should focus on decreasing the bacterial challenge, which may preclude the need to alter the host response. In addition, when a therapeutic modality is selected, it is recommended that it would be prudent to consider a variety of treatment methods prior to administering a host-modulating drug for several months. 4 figures. 6 tables. 21 references.
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Efficacy of Subantimicrobial Dosing with Doxycycline: Point-Counterpoint Source: JADA. Journal of the American Dental Association. 132(4): 457-466. April 2001. Contact: Available from American Dental Association. ADA Publishing Co, Inc., 211 East Chicago Avenue, Chicago, IL 60611. (312) 440-2867. Website: www.ada.org. Summary: This article addresses the role of subantimicrobial dosing with doxycycline (SDD) in the treatment of chronic periodontitis. The authors discuss and debate 10 issues with regard to SDD's usefulness as an adjunct to scaling and root planing. The main focus of this article is data from the U.S. Food and Drug Administration's phase 3
Studies
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clinical trial that evaluated the efficacy of SDD in terms of alterations of probing depth, clinical attachment levels, and disease progression. The authors compared data from test groups, which underwent root planing plus SDD, with data from control groups, which underwent root planing alone. The mean data suggest that SDD provides limited improvement of periodontal status when used in conjunction with scaling and root planing. Furthermore, several in vivo studies indicated that a nine month course of SDD did not cause development of drug resistant bacterial strains or alteration of the subgingival microbiota. The authors caution that there are several issues that should be clarified before widespread use of SDD is recommended for patients with chronic periodontitis. The authors conclude that the evidence indicates that suppression of the bacterial challenge, which reduces the host response, is the most efficient way to control periodontal diseases. 6 tables. 51 references. •
Subantimicrobial Dose Doxycycline: Another Perspective. (commentary) Source: Journal of Practical Hygiene. 11(5): 25-26. September-October 2002. Contact: Available from Montage Media Corporation. 1000 Wyckoff Avenue, Mahwah, NJ 07430-3164. (201) 891-3200. Summary: This commentary addresses some of the issues brought up in an accompanying research article in the same journal. The research article reviews important background material regarding the pathophysiology of periodontitis and raises a number of concerns regarding the clinical utility of subantimicrobial dose doxycycline (SDD) in the treatment of chronic periodontal diseases. The commentary author notes that in a clinical discipline such as periodontics, where much remains unknown, there is more than one way to interpret the data found from the research study. The commentary author concludes that SDD may play a beneficial adjunctive role in some periodontal patients, some of the time. The difficulty is to determine who these patients are, when it may help them, and how often they might need additional rounds of therapy with or without DSS. The commentary author cautions that the inappropriate use of SDD appears real, primarily by those few practitioners who remain loathe to make appropriate referrals of patients who would better benefit from timely interventions provided under the guidance of periodontal specialists.
Federally Funded Research on Doxycycline The U.S. Government supports a variety of research studies relating to doxycycline. 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 doxycycline.
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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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Doxycycline
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 doxycycline. The following is typical of the type of information found when searching the CRISP database for doxycycline: •
Project Title: AKT2 ONCOGENE AND HUMAN ONCOGENESIS Principal Investigator & Institution: Cheng, Jin Q.; Moffitt Cancer Center; University of South Florida 4202 E Fowler Ave Tampa, Fl 33620 Timing: Fiscal Year 2003; Project Start 19-SEP-1997; Project End 31-MAY-2008 Summary: (provided by applicant): We recently cloned the AKT2 promoter and an AKT2-associated protein, NGB, which possesses GTPase and GTP-binding activities. The AKT2 promoter contains a number of transcription factor-binding sites and is induced by v-src and MyoD. Ectopic expression of NGB in tumor cells exhibits tumor suppressor activity. AKT2 interacts with, phosphorylates NGB and abrogates NGBinhibited cell proliferation. Moreover, mutations of NGB were detected in 5 of 27 gliomas examined but not in matched normal DNA. In addition, we have demonstrated that AKT2 interacts with and phosphorylates tuberous sclerosis (TSC) 2 tumor suppressor as well as down-regulates TSC1 and TSC2 proteins, cDNA microarray analyses with RNA prepared from doxycycline-inducible constitutively active (myrAKT2) and dominant negative AKT2- transfected cells revealed that of 12,000 genes examined, 68 genes were changed more than 5 folds. The gene that showed the largest increase in myr-AKT2 cells is the hHbl-deltaN gene. We have detected frequent upregulation of this gene in human cancer cell lines and primary tumors. Moreover, ectopic expression of the hHbl-deltaN induces cell survival, growth and transformation and activates AKT2 pathway, indicating that hHbl- deltaN plays an important role in AKT2 function. Based on these data, we hypothesize that the AKT2 is regulated by oncogenic transcription factors and that AKT2 and its associated proteins, NGB and TSC2, as well as its transcriptionally regulated gene(s) play a pivotal role in the control of cell proliferation and transformation. The broad, long-term objective of this project is to elucidate the normal cellular function of the AKT2 protein and determine the importance of perturbations of the AKT2 pathway in human oncogenesis. The specific aims are: (1) Identify the DNA response elements and transcription factors that regulate AKT2. (2) Define the role of the AKT2-associated protein NGB in AKT2 signaling. (3) Examine the effects of AKT2 phosphorylation of TSC2 on TSC1/TSC2 function. (4) Characterize the AKT2-transcriptionally regulated gene hHbl-AN identified by cDNA microarray. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen
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Project Title: ANTIBIOTIC THERAPY FOR RHEUMATOID ARTHRITIS (ATRA TRIAL) Principal Investigator & Institution: St Clair, Eugene W.; Duke University Durham, Nc 27706 Timing: Fiscal Year 2001 Summary: Previous randomized, controlled clinical trials suggest that oral tetracyclines may reduce the symptoms of joint inflammation in rheumatoid arthritis (RA). This class of antibiotics has well-described antimicrobial effects as well as anti-collagenase activity. Collagenase is an enzyme that degrades cartilage and bone and is believed to be important in the pathogenesis of RA. This study evaluated the safety and potential clinical efficacy of I.V. doxycycline therapy in 31 patients with RA and explored
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whether any improvements in arthritis from the doxycycline were due to its antibacterial actions or ability to reduce the activity of collagenase. The three objectives of this study were: 1) To determine the feasibility, safety, and potential clinical efficacy of I.V. doxycycline therapy in RA and explore whether this agent ameliorates clinical manifestations of this disease by suppressing bacterial infection or matrix metalloproteinases (MMP) activity; 2) To determine whether daily and weekly treatment with I.V. doxycycline can reduce urinary excretion of collagen crosslinks in patients with RA and potentially retard joint damage; and 3) To explore the potential effects of daily and weekly I.V. doxcycline therapy on biochemical markers of cartilage proteoglycan degradation; and 4) to determine whether IV doxycycline can reduce expression of nitric oxide synthase type 2 expressed by circulatory monocytes. Patients were randomized into 3 groups: Group I received I.V. doxycycline and oral placebo, Group II will received I.V. placebo and oral azithromycin, and Group III received I.V. and oral placebo. The I.V. therapy was delivered through a peripheral long-line catheter. The initial treatment phase consisted of daily infusions and oral therapy for 21 days. The second treatment phase consisted of weekly infusions administered from week 4 through 11. Results: The study is closed and a Final Report was submitted to the NIH on December 29, 1998. Thirty-one patients were enrolled between April of 1995 and February 1998. The study population included various ethnic backgrounds, such as African- American, Caucasian, and Native American and was predominantly female (24/7). Only 4 patients withdrew from the trial before the day 112 visit. Three patients discontinued the study drug after day 28 because of worsening arthritis and one patient withdrew at day 56 when she was diagnosed with breast cancer. Thirteen (42%) of the patients experienced at least one infusion-related event during the trial. These events included catheter site tenderness/pain/redness, symptoms of burning during the infusion, site-related skin rash from adhesive tape, catheter infiltration, signs of localized infection at the catheter site, clotting of the catheter or line, and thrombophlebitis. None of these events were classified as serious. Most of the patients experienced at least 1 adverse event, which were most commonly gastrointestinal or neurologic in origin. The most frequent adverse events apart from the infusion-related complications included headache (8 patients), abdominal pain (6 patients), fatigue (6 patients), nausea/vomiting (5 patients, vaginitis (5 patients), loose stools/diarrhea 93 patients), dizziness/lightheadedness (3 patients), and decreased appetite (3 patients). The results of the present study do not provide evidence that i.v. doxycycline therapy reduces the signs or symptoms of RA. These data must be interpreted with caution because the study was not designed to provide adequate statistical power to answer this question. The present study does show that this treatment approach is feasible and does not cause unacceptable toxicities. However, no significant differences were noted among treatment groups in the primary endpoints. The tender joint count dropped only slightly in all of the 3 treatment groups. This result is compatible with little or no immediate clinical effect from the 3 weeks of i.v. doxycycline therapy. Significance: There are no future plans since doxycycline did not improve the primary endpoints. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •
Project Title: ANTIBIOTIC TREATMENT OF CHRONIC LYME DISEASE IN RHESUS MONKEY Principal Investigator & Institution: Philipp, Mario T.; Tulane University of Louisiana New Orleans, La 70118 Timing: Fiscal Year 2001
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Doxycycline
Summary: Backround and Objectives The preferred antibiotic treatment of chronic Lyme disease, and that of chronic neuroborreliosis in particular, is still not fully defined. In an effort to develop improved and more reliable remedies for chronic Lyme disease, an eclectic treatment regimen has been designed. It includes two antibiotics that are highly effective against both acute and chronic Lyme disease ceftriaxone (2 g, IV, once a day, 30 days) and doxycycline (100 mg/kg, bid, per os, 60 days). The goal of this project is to assess the efficacy of this combination regimen, originally devised for humans, in rhesus macaques. More specifically, to monitor the elimination of a Borrelia burgdorferi infection from all organs commonly targeted by this spirochete, and especially from the central nervous system. Results Six rhesus macaques were inoculated with a neurotropic strain of B. burgdorferi (strain NT1) by exposure to infected ticks, and one control animal was exposed to the bite of uninfect ed ticks. All animals were confirmed to be infected by cultivating spirochetes, and amplifying spirochetal DNA by PCR, from skin biopsy samples. Animals were monitored over a six-month period. Unlike previous experiments, in which animals had been infected by needle inoculation with the NT1 strain, no evidence of infection in the central nervous system was obtained. Success in infecting the CNS may thus depend on the inoculum dose, which is likely higher when animals are infected with 108 spirochetes by needle inoculation than by exposure to the bites of ticks. Future Directions The antibiotic efficacy trial will now begin, but needleinoculated animals will be employed. FUNDING NIH-NIAID RO1 AI42352-01 and Base grant. PUBLICATIONS None. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •
Project Title: ANTIGEN-INDUCED B LYMPHOCYTE DEVELOPMENT Principal Investigator & Institution: Fearon, Douglas T.; Director; University of Cambridge Cambridge, England Cambridge, Timing: Fiscal Year 2002; Project Start 20-SEP-2002; Project End 30-JUN-2007 Summary: (provided by applicant): With a long-term objective to understand the developmental stages of the B cell response to antigen, this research will focus on germinal center and memory B cells, which relate to the cardinal features of immunity, affinity maturation of the immune response and immunological memory. The specific aims are to determine: 1) the role of heparan sulfate/heparin in serving as a ligand for CD19 in the germinal center; 2) whether developmental down-regulation of SHP-1 in the germinal center B cell is required, and whether this permits signaling through a gamma-c cytokine receptor; 3) whether arrested terminal differentiation by BCL-6 is the basis for B cell memory; 4) whether signaling through a gamma-c, cytokine receptor is necessary to maintain memory B cells; and 5) whether B cells with dysregulated c-myc present as centroblast-like Burkitt lymphomas because of unique expression patterns of BCL-6 and SHP-l at this stage of development. For Aims 2-5, mice will be created in which transgenes can be inducibly expressed in a lineage-specific manner. A bacteriallyderived transactivator transgene, rtTA, will be expressed only in B cells and will drive transcription of "target" transgenes in the presence of doxycycline. The target transgenes are SHP-1, dominant negative (DN) gamma-c, and wild-type and DN BCL6, all linked via an IRES to EGFP to permit visualization of transgene expression. With doubly transgenic, Fl mice, giving doxycycline will 1) up-regulate SHP-1 and DN gamma-c in germinal center B cells, allowing analysis of the role of low SHP-1 and cytokine receptor signaling in these cells; and 2) up-regulate DN gamma-c, and wild-type and DN BCL-6 in memory B cells, allowing analysis of the role of BCL-6 and cytokine receptor signaling in these cells. The understanding gained from these studies of normal B cell development will be applied to a murine model of Burkitt lymphoma to discover why
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translocation of c-myc at an early stage of B cell development leads to a B cell tumor at a much later stage. 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 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
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Project Title: BIOCHEMICAL BASIS OF KERATOCONUS Principal Investigator & Institution: Yue, Beatrice Y.; Professor; Ophthalmology and Visual Scis; University of Illinois at Chicago 1737 West Polk Street Chicago, Il 60612 Timing: Fiscal Year 2003; Project Start 01-SEP-1981; Project End 30-JUN-2008 Summary: (provided by applicant): Keratoconus (KC) is a noninflammatory disease characterized by thinning and scarring of the central cornea. We have been systematically investigating KC and have accumulated a significant body of information regarding the biologic defects associated with this disabling disease. We have shown that the levels of acid hydrolases, and cathepsins B and G are elevated in KC corneas as compared to normal human and other diseased corneas, whereas the levels of inhibitors
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Doxycycline
such as alpha1-proteinase inhibitor (alpha1-PI) are diminished. These alterations are presumed to perturb the balanced degradation of corneal constituents. The aberrant degradative process is theorized to be the common pathway leading to KC. We have further found that transcription factor Sp1 (Specificity protein 1), at both mRNA and protein levels, is upregulated in KC corneas. During the past grant period, we demonstrated that Sp1 upregulation confers a downregulatory effect on the promoter activity of the a1-PI gene. Our hypothesis is that Sp1 upregulation is a key event that leads to many of the pathologic changes observed in KC. In this renewal application, we propose to investigate, in specific aim 1, the mechanisms by which Sp1 transcript and protein are upregulated in KC corneas. Standard nuclear run-on assays will be performed and the mRNA stability will be evaluated. Since the Sp1 protein is increased beyond the mRNA level, its turnover and phosphorylation and glycosylation status in KC corneas will also be examined and compared with controls. Experiments will in addition be conducted to determine whether the upregulated Sp1 mRNA level is related to aberrations in epigenetic regulatory mechanisms including DNA methylation and histone acetylation. Furthermore, Sp1 downregulation is observed during mouse corneal development. Mechanisms underlying such a downregulation will be explored. In specific aim 2, we will determine the in vivo effects of Sp1 overexpression in the cornea by targeting a Sp1 cDNA to corneal keratocytes under the control of keratocytespecific keratocan promoter utilizing transgenic mouse technology. A binary mouse model will be used to engineer keratocyte-specific Sp1 expression under tetracycline control such that the phenotype can be switched on by feeding the animals doxycycline. Creation of the binary mouse line will be subcontracted to Dr. Chia-Yang Liu at the University of Cincinnati. The mouse will be examined to determine whether thinning of the corneas occurs, the time course, and the effects of environmental factors. In addition, apoptosis and oxidative damage have been proposed recently to be possible pathogenic mechanisms for KC and mutations in the transcription factor VSX1 gene have been identified in KC patients. In specific aim 3, we will investigate the roles of these factors in KC and their possible links to Sp1 overexpression. We will also complete the studies already underway to identify the genes differentially expressed in KC and their biological significance. Through these multiple approaches, we will further delineate cellular and molecular abnormalities in KC. We hope to gain a greater understanding toward the etiologic basis of KC and provide insights to ultimately lead to prevention and treatment of this corneal disease. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •
Project Title: C/EDB BETA AND CHOP IN EPIDERMAL DIFFERENTIATION Principal Investigator & Institution: Maytin, Edward V.; Cleveland Clinic Foundation 9500 Euclid Ave Cleveland, Oh 44195 Timing: Fiscal Year 2001; Project Start 20-AUG-1998; Project End 30-JUN-2003 Summary: Mammalian skin is a vital organ that serves to maintain fluid and electrolyte balance, exclude toxins and pathogens, and participate in immune surveillance. These functions are largely attributable to the epithelial layer of the skin (the epidermis). Derangements in epidermal function in diseases such as psoriasis, or in environmental injuries such as exposure to ultraviolet light, result from abnormalities in the precise balance of keratinocyte proliferation and differentiation that constitute the normal epidermal differentiation program. This balance is regulated within cells at the level of gene transcription by a variety of transcription factors whose identities and mechanisms of action are only now being appreciated. This proposal will test the hypothesis that a relatively new family of nuclear transcription factors, the CCAAT-enhancer binding
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proteins (C/EBPs), plays an important regulatory role in epidermal differentiation. Based upon preliminary data that demonstrate the presence of C/EBPS in keratinocytes of the skin, both in vivo and in vitro, the proposed experiments will establish, in a causal manner, how two members of the C/EBP family (C/EBPbeta and CHOP) may be critical for the proper and orderly progression of the epidermal differentiation program. Stable keratinocyte cell lines, expressing doxycyline-inducible transgenes that encode both activators and inhibitors of C/EBPbeta and CHOP (including antisense RNA, and inhibitory protein isoforms of C/EBPs) will be studied in a calcium-dependent differentiation model in vitro. Alterations in parameters of growth and differentiation will be assayed after induction of the transgenes with doxycycline. As an in vivo correlate to these studies, stable keratinocyte lines will be grafted onto the backs of nude mice, to test for doxycycline-inducible changes in the epidermis formed at the graft site. Results of these studies may enhance our understanding of mechanisms that govern the switch from proliferation to differentiation, and in later events such as apoptosis, in the epidermis. These studies will build a foundation for later studies on the significance of observed changes in C/EBPbeta and CHOP expression in psoriasis and in skin exposed to UV light. Thus, changes in C/EBPbeta and CHOP-regulated gene expression are probably involved not only in the normal balance proliferation and differentiation in the epidermis, but also in epidermal disease and in responses of the skin to environmental injury. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •
Project Title: CAP CELL DERIVED TUMORS--MODEL OF INVASIVE BREAST CANCER Principal Investigator & Institution: Radice, Glenn L.; Obstetrics and Gynecology; University of Pennsylvania 3451 Walnut Street Philadelphia, Pa 19104 Timing: Fiscal Year 2001; Project Start 08-AUG-2000; Project End 31-JUL-2003 Summary: A major problem in breast cancer treatment and the leading cause of mortality is invasion and metastasis of primary breast tumors. Very little is known about the fundamental biology of mammary tumors that can explain why certain tumors are aggressive in some individuals while relatively quiescent in others. The cell type from which the tumor arises may dictate its potential for invasion and metastasis. The mammary gland consists of different cell types including the cap cell; a less differentiated, highly proliferative cell basally located in the terminal end bud (TEB) of the murine mammary gland. The TEBs invade the fatty stroma of the pubertal gland establishing the ductal network. These specialized structures are reported to be targets for carcinogen- induced DNA damage. Their human counterparts are called intralobular ducts and are also sites of cancerous lesions. We hypothesize that genetic change specific to the cap cell population of the TEB will lead to aggressive tumors and metastatic disease. The long term goal of this research is to understand why some breast tumors are benign and others metastatic, and translate this information into better treatment protocols. P-cadherin is normally expressed in the cap cells of the TEB and its progenitors. The recent finding that P-cadherin expression in human breast tumors strongly correlates with poor patient survival suggests two possible explanations. Either P-cadherin expression is upregulated in transformed epithelial cells which normally do not express P-cadherin or these highly invasive tumors originate from a cap cell or stem cell-like progenitor. The experiments outlined in this proposal will directly examine the latter possibility. In order to determine the role of a specific subset of mammary cells in tumorigenesis we will generate an inducible expression system in which transgene expression can be tightly regulated in vivo. The endogenous P- cadherin promoter will
12
Doxycycline
be used to direct expression to the cap cells. The neu/HER-2 proto-oncogene will be induced in cap cells during specific periods of mammary gland development by administration of the tetracycline derivative, doxycycline. Tumor development will be examined in these animals and tumor pathology will be compared to human breast tumors as well as transgenic models. The goal of this research is to determine whether the highly proliferative and invasive cap cell population is a target for metastatic breast cancer. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •
Project Title: CAR & ADENOVIRAL GENE THERAPY FOR DIABETIC RENAL DISEASE Principal Investigator & Institution: Bhatt, Udayan Y.; Internal Medicine; Ohio State University 1800 Cannon Dr, Rm 1210 Columbus, Oh 43210 Timing: Fiscal Year 2003; Project Start 01-MAR-2003; Project End 31-JAN-2008 Summary: (provided by applicant): Replication deficient recombinant adenoviruses (rAv) are potent vectors for DNA transfer (transduction). Diabetic glomerulosclerosis is a potential target for rAv-based forms of gene therapy. The coxsackie adenovirus receptor protein (CAR) mediates rAv infection. Despite widespread use of rAv, the mechanisms of CAR-mediated viral entry into cells are not well characterized. Therefore, the scientific objective of this proposal is to define CAR receptor expression, function, and utility in controlling transduction. The project has 3 Specific Aims. Aim #1 will further characterize the expression of CAR in normal and diabetic kidney. Aim #2 will investigate the functional consequences of rAv engagement of CAR under normal and diabetic conditions. Beginning with DNA microarray analysis followed by confirmatory studies using quantitative PCR, the gene activation profile resulting from CAR engagement by rAv will be elucidated. Aim #3 will explore the clinical utility of CAR in regulating rAv mediated gene transfer. The goal of this aim is to control rAv transduction by using a doxycycline-responsive CAR transgene. Taken together, these studies will define CAR expression, function, and utility in the development of rAvbased forms of gene therapy for diabetic glomerulosclerosis. The scientific goals of this project are a natural extension of the candidate's current studies (NIH 1F32 DK1006401). The educational curriculum developed by the candidate and his sponsors will complement the scientific studies in developing a comprehensive training experience. The educational curriculum employs a multi-faceted approach consisting of didactics, seminars, and meetings. These activities provide the foundation for the applicant in the pursuit of a career as a physician scientist. The long-term career goal is to develop into a translational scientist with all of the clinical and basic investigative tools necessary to design and apply novel forms of gene therapy for kidney disease. In this regard, the candidate will continue his relationship with his current mentor, N. S. Nahman, Jr., M.D. Dr. Nahman provides an excellent role model as a clinician scientist. Chandan K. Sen, Ph.D., serves as a cosponsor on the project and brings a diverse background in the basic sciences for the candidate's training plan. Thus, the candidate's scientific plan, educational curriculum, and association with effective mentors ensure an excellent career development experience. 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.; Director, Degenerative Disease; Burnham Institute 10901 N Torrey Pines Rd San Diego, Ca 92037
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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 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: CEFTRIAXONE AND DOXYCYCLINE IN PATIENTS WITH SERONEGATIVE CHRONIC LYME DISEASE Principal Investigator & Institution: Klempner, Mark S.; New England Medical Center Hospitals 750 Washington St Boston, Ma 021111533 Timing: Fiscal Year 2001 Summary: These studies will explore treatment strategies for chronic lyme disease and will be conducted at two centers, New England Medical Center/Tufts University School of Medicine and Westchester County Medical Center affiliated with New York Medical College. The coordinating center, and the central laboratory facility will be at New England Medical Center. Investigators will perform an initial assessment of each patient for collection of demographic data, a history of exposure to ticks in geographic regions with endemic B. burgdorferi infection. Treatment interventions and clinical endpoints will be assessed. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen
14
Doxycycline
•
Project Title: CEFTRIAZONE&DOXYCYCLINE IN SEROPOSTIVE CHRONIC LYME DISE Principal Investigator & Institution: Evans, Janine; Yale University 47 College Street, Suite 203 New Haven, Ct 065208047 Timing: Fiscal Year 2001 Summary: The primary objective of this study is to determine whether; 1) intensive antibiotic treatment benefits seropositive patients with Chronic Lyme Disease: 2) evidence of persistent infection with Borrelia burgdorferi can be found in patients with CLD: 3) evidence of co-infection with other microorganisms can be found in patients with CLD: 4) specific clinical or laboratory parameters improve in patients who receive antibiotic therapy compared to patients who receive placebo and 5) specific parameters are predictive of a response to therapy should it be observed. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen
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Project Title: CONDITIONAL MODULATION OF MYOSTATIN EXPRESSION IN SKELETAL MUSCLE OF MICE Principal Investigator & Institution: Reisz-Porszasz, Suzanne; Charles R. Drew University of Med & Sci 1621 E 120Th St Los Angeles, Ca 90059 Timing: Fiscal Year 2003; Project Start 01-JUL-2003; Project End 30-JUN-2007 Summary: Myostatin (Mst) is a negative regulatory protein of skeletal muscle mass during embryological development. Spontaneous or induced inactivating mutations of Mst are associated with considerable increase of skeletal muscle, suggesting that myostatin is an important genetic determinant of muscle mass. Elevated levels of Mst are associated with skeletal muscle loss in adult animals and humans, but a clear cause/effect relationship has not been established, and the role of Mst protein in regulating muscle mass in adult animals remains poorly understood. In this proposal we hypothesize that a transgenic mouse able to hyperexpress myostatin in the skeletal muscle by pharmacological modulation, will lose muscle mass and impair its function in response to the activation of this process, through a reduction in the number and size of muscle fibers, and that these effects are age and gender dependent. This would demonstrate conclusively that Mst is a key negative regulator of muscle mass and function in postnatal life. The following aims are proposed: 1) We will generate a conditional Mst hyperexpression transgenic (CMHT) mouse, where Mst expression is activated at the desired periods in adulthood by doxycycline (Dox). We will use the gene expression system, Tet-On, based on a regulatory construct driven by the mouse muscle creatine kinase (MCK) promoter, and a response construct of the mouse Mst cDNA, or alternatively a single construct with sequences in tandem. Constructs will be tested in vitro in HEK 293 Tet-On approved transformed primary embryonal kidney cell and C2C12 myoblast, myotube cells and used to originate the respective transgenic animals. 2) We will turn recombinant Mst expression on in male and female mice at the ages of 7 weeks, 6 and 18 months, for different periods, and measure muscle and fat mass, fiber size and composition, muscle strength and endurance, and energy expenditure, in correlation with myostatin expression, determined by real time RT/PCR, northern and western blot. 3) We will determine whether turning off recombinant myostatin expression will reverse the effects in an age- and genderdependent process that can be modulated by exercise training. This study may conclusively determine that hyperexpression of myostatin causes muscle wasting in the adult animal and may open the way to prevent or reverse aging-related sarcopenia via the inhibition of Mst expression and/or activity.
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Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •
Project Title: CONTROL OF MENSTRUAL BLEEDING DISTURBANCES IN WOMEN Principal Investigator & Institution: Fraser, Ian S.; Sydney Centre for Reproductive Hlth Res Health Research Ashfield, Timing: Fiscal Year 2002; Project Start 27-SEP-2002; Project End 30-JUN-2007 Summary: (provided by applicant): This application is designed to evaluate two promising approaches to the treatment of prolonged and frequent episodes of breakthrough bleeding which sometimes accompany the use of the implantable, progestogen-only implant Implanon. These erratic episodes of bleeding can be a major reason for discontinuation of use. There is increasing evidence that continuous exposure to progestogens results in a tendency for the endometrium to release active enzymes called matrix metalloproteinases [MMPs] which can promote premature breakdown of the tissue. Inhibition of the action of these enzymes may stabilize the endometrium and improve the bleeding pattern. A commonly used tetracycline compound, Doxycycline, has strong anti-MMP action and preliminary evidence in a mouse model of menstruation suggests that it may indeed stabilize the endometrium. There is preliminary evidence that a short course of an antiprogesterone (Mifepristone) may also stabilize the endometrium, and it is postulated that a combination of an antiprogesterone with estrogen may be even more effective. Preliminary evidence in mice indicates that estrogen exposure of the endometrium in the absence of progesterone strongly inhibits the formation of new blood vessels and simultaneous anti-progesterone exposure will mimic this situation. Antiprogesterones probably also have a direct effect in inhibiting angiogenesis, and the combination maybe a clinically valuable treatment. A triple combination of antiprogesterone, estrogen and anti MMP agent may have additive effects because of the likelihood of differing actions. This study aims to explore these possibilities in large scale clinical studies, scientific study of vascular and molecular changes in endometrium and with the exploration of molecular mechanisms in mice. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen
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Project Title: CONTROLLING THE BCL-2 PATHWAY OF MITOCHONDRIAL APOPTOSIS Principal Investigator & Institution: Letai, Anthony G.; Dana-Farber Cancer Institute 44 Binney St Boston, Ma 02115 Timing: Fiscal Year 2003; Project Start 07-JUL-2003; Project End 30-JUN-2008 Summary: (provided by applicant): Cancer cells frequently and perhaps invariably possess aberrations in the genetic pathway of programmed cell death. The BCL-2 family of proteins plays a critical role in the signaling and execution of death signals. A common mechanism by which cancer cells evade programmed cell death is by altering the ratio of antiapoptotic/ pro-apoptotic BCL-2 members, resulting in a functional excess of BCL-2 antiapoptotic molecules. This proposal describes strategies to test the hypotheses that (a) anti-apoptotic BCL-2 family members can be specifically targeted, and (b) BCL-2 is a valid target for anti-cancer therapy. To address (a), binding interactions between anti-apoptotic BCL-2 family members and BH3 domains from "BH3-only" family members will be examined using fluorescence polarization to determine the specificity of interaction between the two classes of proteins. The relevance of the binding interactions will be validated using functional mitochondrial
16
Doxycycline
and cellular assays of apoptosis. From these studies will emerge oligo-peptides which function as prototype inhibitors of anti-apoptotic BCL-2 family members. This approach has already shown promise in the preliminary characterization of a peptide inhibitor of BCL-2 based on the BH3 domain of BAD. To address (b), a mouse model of leukemia which is dependent on BCL-2 for maintenance is described. In this model, mice develop a lymphoid leukemia which remits when expression of BCL-2 is eliminated by treatment with doxycycline. To test the importance of BCL-2 in tumor maintenance in other tissue types, the conditional expression of BCL-2 will be extended to other tissues such as breast and melanocytes. Methods are described for the promotion of cancer in these models. When cancer develops, BCL-2 expression will be controlled by doxycycline to determine if BCL-2 is required for tumor maintenance. Finally, we will use the mitochondrial, cellular and mouse assays developed above to test the efficacy and specificity of BH3 mimetics of both small molecule and peptidomimetic origin. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •
Project Title: COX-2 AND P53 INTERACTIONS AND CANCER PREVENTION Principal Investigator & Institution: Sheikh, M Saeed.; Associate Professor; Pharmacology; Upstate Medical University Research Administration Syracuse, Ny 13210 Timing: Fiscal Year 2003; Project Start 30-SEP-2003; Project End 31-AUG-2005 Summary: (provided by applicant): Cyclooxygenase 2 (COX-2) is overexpressed in human malignancies and is a promising target to develop novel chemopreventive strategies. Clinical trials are currently in progress to investigate the efficacy of COX-2 selective non-steroidal anti-inflammatory drugs in the prevention of various types of cancers. However, much remains to be elucidated as to how COX-2-selective agents mediate chemopreventive effects. A better understanding of the molecular mechanisms that regulate COX-2 expression will certainly facilitate the development of more effective and less toxic cancer-preventive strategies. In this regard, the tumor suppressor p53 has been found to promote upregulation of COX-2 mRNA and protein levels. COX2 has been implicated in positive growth regulation and tumorigenesis while tumor suppressor p53 is a negative regulator of growth. Thus, p53-dependent upregulation of COX-2 appears rather incongruous. It has been proposed that p53-dependent COX-2 upregulation could be a mechanism to abate the apoptotic effects of p53. The work proposed in this two-year pilot study will directly evaluate the hypothesis that p53dependent COX-2 upregulation is a compensatory response that serves to abate the p53induced apoptosis. In order to accomplish our goals, we have proposed two specific aims. In Specific Aim 1, we will investigate whether COX-2 negatively affects the function of wild type p53. We will establish tetracycline or doxycycline-inducible COX-2 and p53 double-inducible cells to investigate whether COX-2 negatively affects the function of wild type p53. By using the double-inducible cells that would exhibit simultaneous induction of COX-2 and p53, we will ensure that higher levels of COX-2 are available from the beginning. Thus, if COX-2 negatively affects the function of wild type p53 then it will be instantly available to mediate its effect on p53. In Specific Aim 2, we will abrogate COX-2 expression via RNA interference approach to test the effect of COX-2 deficiency on p53 functions including p53-induced apoptosis. Thus, investigating the molecular mechanisms that control the interplay between COX-2 and p53 activities is relevant and the outcome, if successful, would improve our understanding of the malignant development and progression to further the progress in developing novel, more effective and less toxic cancer-preventive strategies. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen
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17
Project Title: DEVELOPMENT OF A DOXYCYCLINE-INDUCIBLE HIV-1 VECTOR Principal Investigator & Institution: Smith, Stephen M.; Saint Michael's Medical Center 268 Dr. Martin Luther King Blvd Newark, Nj 07102 Timing: Fiscal Year 2001; Project Start 01-JUN-2000; Project End 31-MAY-2002 Summary: (Adapted from Applicant's Abstract) The main objective is to develop a form of HIV which will replicate only in the presence of the drug, doxycycline. Current liveviral vectors for HIV and other viruses cannot be conditionally controlled. These viruses, however attenuated, replicate in vivo to the extent permitted by the host's cells and immune system. Investigators have previously described a promoter-transactivator system that is active only in the presence of doxycycline. In this system the transactivator, RTTA, binds to the tet operator sequences only in the presence of doxycycline. When bound to the tet operator sequences, RTTA potently activates this promoter. HIV transcription is naturally under the control of the TAR-Tat interaction. Tat binds to TAR and activates the HIV promoter via interaction with host cell proteins. This form of activation is not amenable to exogenous control. HIV-Dox is being developed to allow conditional control of the activation process. In HIV-Dox, Tat cannot bind to TAR, which has been mutated. Without the TAR-Tat interaction, natural transcription is greatly reduced. Additional mutations in the U3 region of the LTR have been made to reduce the basal level of transcription even further. Upstream of the HIV TATAA box in HIV-Dox, tet operator sequences have been cloned. The gene for RTTA has been placed into the nef reading frame. In transient transfections, HIV-Dox virus production is dramatically upregulated in the presence of doxycycline (>100-fold increase). However, we have been unable to detect replication of HIV-Dox in CD4+ cells (by p24 ELISA or RT assay). The goals of the project are to determine why HIV-Dox does not replicate productively in T-cell lines and to repair this defect in order to obtain a doxycycline-inducible HIV vector. HIV-Dox would then be converted to SIV-Dox, which could be further developed in the macaque model of AIDS. After the safety and efficacy of SIV-Dox has been determined in macaques, HIV-Dox may be similarly developed as a potential vaccine in humans. In this scenario, the host, after receiving HIV-Dox, would be administered doxycycline for a defined period of time. While the host received doxycycline, HIV-Dox would replicate productively; this replication would induce an immune response. After the immune response has matured, the doxycycline administration would be discontinued and HIV-Dox would stop replicating. In this way, vaccine related disease could be reduced. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen
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Project Title: DIFFERENTIAL CHEMOKINE GENE EXPRESSION IN THE LUNG Principal Investigator & Institution: Ray, Prabir; Associate Professor; Internal Medicine; Yale University 47 College Street, Suite 203 New Haven, Ct 065208047 Timing: Fiscal Year 2001; Project Start 01-APR-1998; Project End 30-JUN-2001 Summary: We previously reported the cloning of a gene IkappaBR from lung epithelial cells. Recently we have shown that overexpression of IkappaBR in lung epithelial cells results in upregulation of RANTES but not interleukin-8 (IL-8) gene expression despite the fact that both genes are regulated by NF-kappaB. This selective upregulation correlated with increased binding of a unique RANTES-kappaB binding activity and decreased binding of p50 homodimers which are known to function as repressors of certain kappaB sites. Taken together, these observations prompted us to hypothesize that: 1. Unique NF-kappaB family proteins exist in epithelial cells which can selectively upregulate chemokine gene expression in lung inflammation. 2. The ability of IkappaBR
18
Doxycycline
to sequester inhibitory p50 homodimers plays an important role in this process. To address this hypothesis we will: Aim # I. Characterize the cell-specificity and mechanisms of IkappaBR-mediated RANTES gene upregulation. (a) Whether different stimuli that activate RANTES gene expression such as cytokines and viruses also augment IkappaBR gene expression will be investigated. (b) RNase protection assays, DNA footprinting assays, enzyme-linked immunosorbent assays and electrophoretic mobility shift assays will be used to study the effect of IkappaBR overexpression on RANTES and IL-8 gene expression in different cell types. (c) A dominant negative form of IkappaBalpha (IkappaBalphaM) in an inducible fashion in IkappaBR-overexpressing lung epithelial cells to determine the requirement for the classical p50/p65 heterodimer in RANTES gene expression in these cells. (d) The effect of specific inhibitors of NFkappaB (p50/p65) activation on RANTES gene expression and formation of the unique complex will be studied. Aim # II. Characterize the proteins constituting the unique complex. A molecular cloning approach, the yeast two-hybrid system, will be used to characterize the unique RANTES-kappaB binding complex. Aim # III. Investigate the expression of IkappaBR in human asthma and the effect of overexpression of IkappaBR or IkappaBalphaM on RANTES gene expression in mice using an inducible transgenic system. (a) In situ hybridization techniques will be used to determine whether IkappaBR gene expression is upregulated in human asthma. (b) The doxycycline-inducible transgenic system recently established in our laboratory will be used to overexpress IkappaBR or IkappaBalphaM in vivo. (c) The effect of IkappaBR or IkappaBalphaM overexpression on RANTES gene expression will be investigated in antigen and viral models of airway inflammation. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •
Project Title: DOXYCYCLINE EFFECT ON OSTEOARTHRITIS PROGRESSION Principal Investigator & Institution: Brandt, Kenneth D.; Professor; Medicine; Indiana Univ-Purdue Univ at Indianapolis 620 Union Drive, Room 618 Indianapolis, in 462025167 Timing: Fiscal Year 2001; Project Start 30-SEP-1996; Project End 31-JUL-2003 Summary: (from the application): Osteoarthritis (OA) of the knee is the most common cause of chronic disability in this country and has enormous socio-economic impact. Notably, management of OA today is limited to symptomatic therapy. Nonsteroidal anti-inflammatory drugs (NSAIDs) are the most popular agents used to treat OA but elderly women, in whom OA is especially common, are at greatest risk of developing serious side effects from NSAIDs. Notablly, however, several drugs have been shown to prevent, or slow progression of, cartilage damage in animal models of 0A, and drugs are currently being developed to inhibit protease-induced cartilage damage, with a view to their use in OA. We have shown that prophylactic oral administration of doxycycline (doxy) markedly reduces the severity of cartilage damage in a canine model of OA; even when therapy was initiated after cartilage lesions were established, a protective effect was apparent. Similar results have been noted in guinea pig and rabbit models of OA. The effect is associated with reduction in the levels of collagenase and gelatinase in the OA cartilage. Based on the encouraging data in animal models of OA, we propose to conduct a multi-center, double-blind, placebo-controlled clinical trial of doxy in subjects with OA. It is our hypothesis that doxy will decrease the severity, or rate of progression, of OA. Because a disease-modifying drug for OA will, presumably, be more likely to show an effect in the early stages of the disease than when OA pathology is more advanced, our study population will be 2 obese females, 45-60 years old, with x-ray evidence of unilateral tibiofemoral OA in whom x-ray changes have been reported to
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develop in the contralateral knee in nearly 50% within 2 years. Subjects (n=432) will be randomized to receive doxy, 100 mg bid, or placebo for 2-1/2 years. No attempt will be made to influence NSAID and/or analgesic treatment or other measures prescribed in the course of routine clinical care. Several strategies will be employed to maximize compliance with the study medications and retention of subjects in the study, including a "faintness-of-heart" test, which will be used at the outset to eliminate noncompliers, and use of a computerized medicine cap to provide information concerning compliance with the prescribed dosing regimen between visits, permitting study personnel to aim their efforts to enhance compliance at those subjects who can best benefit from them. Our primary outcome variables will be the rate joint space narrowing (JSN, measured by a computerized system on a digitized AP radiograph of the semi-flexed knee taken with a technique to markedly reduce variability in radioanatomic positioning) and the severity of individual radiographic features of OA, e.g., osteophytes, in the contralateral knee. Because the rate of JSN in the contralateral knee is uncertain, whereas published data indicate that in knees which exhibit bony changes of OA (e.g., osteophytes) it is sufficiently rapid to permit detection of a reasonable drug effect during the study period, radiographic progression in the index knee will also serve as a primary outcome variable. In addition, we will examine changes in an algofunctional index (WOMAC), global arthritis activity, general health status (SF-36). and utilization of health services in the two treatment groups. This study should answer the question whether oral treatment with doxy - a relatively safe, readily available and inexpensive drug with which decades of clinical experience have accrued - can modify the natural history of OA in humans. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •
Project Title: DOXYCYCLINE CONTRACEPTORS
FOR
BLEEDING
IN
PROGESTIN
ONLY
Principal Investigator & Institution: Archer, David F.; Director, Clinical Research Center; Obstetrics and Gynecology; Eastern Virginia Medical School Norfolk, Va 23507 Timing: Fiscal Year 2002; Project Start 27-SEP-2002; Project End 30-JUN-2007 Summary: (provided by applicant): Clinically, a high percentage of women using progestin-only contraception experience breakthrough bleeding spotting that causes impaired lifestyle and results in decreased compliance with this contraceptive method. There is a need for an effective, low-cost, easily adapted treatment to reduce the bleeding and spotting in progestin only contraceptives. The molecular environment of the endometrium of women with breakthrough bleeding [BTB] and spotting, like many other inflammatory disorders, contains abnormally high levels of pro-inflammatory cytokines (TNF-alpha and IL-1beta)and abnormally high levels of proteases (matrix metalloproteinases [MMPs] and neutrophil elastase), which prevent normal tissue repair. Doxycycline [DOX] is an inexpensive, FDA approved antibiotic that inhibits MMPs, TACE activity, and reduces NO synthesis. The therapeutic benefit of DOX in animal models and clinical studies of periodontal and ulcerative diseases is due to its inhibition of MMPs, not to its antibiotic effect. We do not anticipate any reduction in contraceptive efficacy with the use of DOX. We propose to clinically evaluate DOX treatment of progestin-only contraceptive induced BTB and spotting, and to biochemically characterize the endometrial molecular biologic changes that occur in DOX treated patients. If successful, DOX treatment could become an important adjuvant for treatment of this and possibly other inflammatory disorders effecting reproductive tract tissues. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen
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Doxycycline
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Project Title: EFFECT OF ANTIBIOTICS ON ORAL BIOFILMS IN VIVO Principal Investigator & Institution: Haffajee, Anne D.; Senior Member of Staff; Forsyth Institute Boston, Ma 02115 Timing: Fiscal Year 2001; Project Start 01-SEP-1999; Project End 30-JUN-2003 Summary: Biofilms found on mammalian tissue surfaces contain complex mixtures of bacterial species growing within a glycocalyx matrix. Species in biofilms have shown remarkably greater resistance to antibiotics than when grown in a planktonic state. Surprisingly little is known about the effect of systemically administered antibiotics on the microbial composition of naturally occurring, complex biofilms. Thus, the long-term objective of this proposal is to determine the effect of antibiotics on the microbial composition of biofilms as they exist in vivo and to determine if the proportion and nature of antibiotic resistant taxa is affected. Subgingival biofilms that occur on teeth will be employed as a model system because of their complexity, ready accessibility and known microbial composition. Specific Aim 1 will examine the effects of 3 systemically administered antibiotics on the microbial composition of subgingival biofilms in adult humans with periodontitis. All subjects will receive scaling and root planing and will be randomly assigned to one of 4 groups of 36 subjects each receiving one of doxycycline, amoxicillin, metronidazole or control. 28 subgingival biofilm samples will be taken in each subject at baseline, at selected time points while the agent is being taken, the same time points after cessation of the agent as well as at 3, 6 and 12 months. These samples will be evaluated individually for their content of 40 subgingival species using checkerboard DNA-DNA hybridization. Data will be evaluated longitudinally and compared with clinical parameters. Specific Aim 2 will examine the proportion and nature of subgingival species that are resistant to 4 mug/ml of the test antibiotic at the same time points. Subgingival biofilm samples will be plated on media with and without the test antibiotic and resistant isolates identified using DNA probes. Data from this investigation will indicate the kinetics of suppression of species in subgingival biofilms during antibiotic administration, the kinetics of repopulation after antibiotic withdrawal as well as the nature and proportion of subgingival species that are resistant to the antibiotics at different time points. The data should indicate the effects of antibiotics on the microbial composition of complex ecosystems such as those found in biofilms and be useful in guiding and interpreting in vitro studies of mechanisms of antibiotic resistance. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen
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Project Title: EFFECT OF DOXYCYCLINE ON OSTEOARTHRITIS PROGRESSION Principal Investigator & Institution: Manzi, Susan M.; Associate Professor of Medicine and Epid; University of Pittsburgh at Pittsburgh 350 Thackeray Hall Pittsburgh, Pa 15260 Timing: Fiscal Year 2001 Summary: This is a six center, double-blind, placebo-controlled study to determine if the administration of oral doxycycline will decrease the severity or progression of osteoarthritis (OA) in females. This is a 30 month clinical trial. Because the pathologic changes of OA progress slowly, obese women between ages of 45-64 with radiographic evidence of unilateral knee OA will be used as subjects. Our primary outcome measure will be radiographic OA progression in the contralateral knee. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen
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Project Title: EXPERIMENTAL MACAQUE PELVIC INFLAMMATORY DISEASE Principal Investigator & Institution: Patton, Dorothy L.; University of Washington Seattle, Wa 98195 Timing: Fiscal Year 2001 Summary: This study is designed to investigate several factors of the immune response to cervical chlamydial challenges, including genetic predisposition to progression of disease, specific immune responses (cytokine activity) to chlamydial infection, and identification of chlamydial antigen in tissues. Effectiveness of treatment is also being assessed in doxycycline- vs. azithromycin-treated animals, for lower and upper reproductive tract chlamydial infections. Studies specific to cytokine expression and immune responses to upper vs. lower tract disease are ongoing. Treatment assessments thus far have indicated that 3 of 7 doxycycline-treated animals failed treatment, compared with 1 of 4 azithromycin-treated animals. Of 7 animals receiving placebo treatment, 6 remained culture and/or LCR positive at the site of the cervix after completion of treatment. All animals were randomly assigned to treatment groups. The placebo treatment group is larger so that untreated animals ca n be followed for progression of disease studies. MHC testing has been performed on all 18 monkeys, though analysis of these results will take place after completion of all 45 animals to be enrolled in these studies. The analysis will be dependent on disease outcome for each animal. FUNDING NIH grants RR00166 and AI40307. Patton, D.L. and Lichtenwalner, A.B. Animal models for the study of chlamydial infections. In Chlamydial Infections, edited by R. Stephens et al., p. 641-650, 1998. Patton, D.L., Cumming, P.K., Cosgrove Sweeney, Y.T., and Kuo, C.C. In vivo uptake of Chlamydia trachomatis by fallopian tube epithelial cells is rapid. In Chlamydial Infections, edited by R. Stephens et al., p. 87-90, 1998. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen
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Project Title: FORMATION AND TOXICITY OF PERIPHERIN INCLUSIONS Principal Investigator & Institution: Julien, Jean-Pierre; Professor; Montreal General Hospital 1650 Cedar Ave Montreal, Timing: Fiscal Year 2001; Project Start 06-SEP-2001; Project End 31-AUG-2005 Summary: (provided by applicant): The presence of abnormal inclusions of intermediate filaments (IFS) in motor neurons represents a common pathological feature of amyotrophic lateral sclerosis (ALS). The majority of these inclusion bodies are composed of neurofilament (NF) proteins together with peripherin, a type III IF normally expressed at low levels in motor neurons. Recently, we discovered that the overexpression of wild-type peripherin proteins in mice provokes the formation of IF inclusion bodies and late-onset death of motor neurons. Moreover, the disease was precipitated by a deficiency in levels of NF light (NF-L) proteins, a phenomenon associated with ALS. A number of experiments are proposed here to further determine whether peripherin abnormalities may contribute to ALS pathogenesis. We will generate a new transgenic mouse model with the onset of peripherin inclusion formation, modulated by the doxycycline control of transgene expression. We will study the mechanisms regulating the formation and toxicity of peripherin aggregates in neurons. Previous results demonstrated an upregulation of peripherin expression by pro-inflammatory cytokines and by excitotoxic injury. It is proposed, with the use of cultured cells and of transgenic mouse approaches, to further define the regulatory elements activating peripherin gene transcription and to determine whether induction of peripherin levels contributes to neuronal loss after cerebral ischemia and excitotoxic
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Doxycycline
injury. In addition, the gene knockout approach will allow us to determine the contribution of peripherin to pathogenesis in two established mouse models of motor neuron disease, mice expressing mutant superoxide dismutase linked to ALS and mice carrying the wobbler mutation. Finally, we will search for peripherin gene mutations in familial and sporadic cases of ALS. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •
Project Title: FURTHER STUDIES ON ANTI HIV 1 ACTIVITY OF INTERLEUKIN 16 Principal Investigator & Institution: Zhou, Paul; Southwest Foundation for Biomedical Res San Antonio, Tx 782450549 Timing: Fiscal Year 2001; Project Start 01-JUL-2000; Project End 30-JUN-2004 Summary: Interleukin 16 is a potent anti-HIV-1 agent. Previously, we demonstrated that at subnanomolar concentrations the C-terminal 130-amino acids (aa) of IL-16 constitutively secreted by CD4 transfectants renders these cells resistant to HIV-1. We and others also demonstrated that in CD4 T cells, IL-16 mediated HIV inhibition through repression of HIV LTR activity. In this proposal we will focus on three aspects of anti-HIV-1 activity of IL-16. First, we will search for more stable, potent version of IL16 and molecularly dissect its anti-HIV and chemoattractant activities. We will make gene constructs expressing several modified versions of human IL-16 with a heterologous signal peptide. Stable human CD4 transfectants will be generated. The expression, stability, secretion, and anti-HIV-1 activity of these various versions of IL-16 will be compared. We will also generate several single point mutants of IL-16 to dissect their anti-HIV and chemo attractant activities. Second, we will test the synergy between IL-16 and chemokines in anti-HIV-1 activity. We will generate retroviral gene constructs expressing IL-16 and methionine-modified RANTES or methionine-modified SDF-1beta. The recombinant retroviral particles produced by stable packaging cells will be used to transduce primary human CD4 T cells. The expression of transgenes and the effect of transgene products on both macrophage-tropic and T cell line-tropic HIV-1 replication, CD4, CXCR4 or CCR5 expression, and cell growth will be tested. In parallel, we will make rIL-16, rMet-SDFlbeta, and rMet-RANTES in bacteria. The synergy of these proteins in anti-HIV activity will be quantified. Third, we will develop an ex vivo procedure to regulate IL-16 and chemokine expression in a murine model. Using this model, the long-term regulation and safety of IL-16 and chemokine secretion in vivo will be evaluated. We will generate retroviral constructs co-expressing murine IL-16 and Met-RANTES or Met-SDF-lbeta under a tetracycline-inducible promoter. The inducibility of transgene expression will be tested in genetically manipulated mouse CD4 T cells in vitro. If the results are encouraging, we will transplant these cells into syngeneic mice. The level of transgene expression will be regulated by doxycycline administered in drinking water. TheserumlevelofIL16andchemokinesandpotentialsignsof inflammation will be closely monitored. We hope these studies will lead to an IL-16- and chemokine-based therapeutic strategy for the treatment of AIDS. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen
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Project Title: INHIBITORS
GENE
BASED
APPROACH
TO
TREATING
HEMOPHILIC
Principal Investigator & Institution: High, Katherine A.; Professor of Pediatrics; Stanford University Stanford, Ca 94305
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Timing: Fiscal Year 2001 Summary: Hemophilia has proven a fruitful model for the study of gene-based approaches to the treatment of disease, and it seems likely that such an approach will be developed for widespread application in the near future. A substantial proportion of patients with severe hemophilia, develop inhibitory antibodies to infused clotting factor, which they perceive as a "foreign" protein. These individuals fail to respond to clotting factor concentrates and until recently presented one of the most difficult management problems in hemophilia Experience over the past decade has shown that administration of recombinant F.VIIa in doses sufficient to achieve circulating levels of 2-4mug/ml levels can result in effective hemostasis in individuals with inhibitors. In this application we propose to develop a gene-based approach to administration of VIIa in hemophilic animals where inhibitor formation has been induced. Building on our success with AAV vectors administered to liver, we will develop AAV vectors that express an engineered F.VII construct that is cleaved to F.VIIa intracellular and secreted as the activated form. In aim 1, we will carry out short-term experiments to determine whether we can achieve hemostasis in a mouse model of hemophilic inhibitors by portal vein injection of an AAV-F.VIIa vector. In the second aim we will carry out long-term studies of clotting parameters in mice that continuously express F.VIIa at a series of defined levels. The purpose of these experiments is to determine whether there is any baseline level of F.VIIa expression that will result in improvement in clotting parameters without serious adverse effects. In the second part of this aim we will develop AAV-VIIa vectors controlled by a "switch" that can be activated by the drug doxycycline, and determine whether such a system can be used to reduce unwanted side effects associated with long-term expression of VIIa, yet still serve to prevent bleeding in response to a hemostatic challenge. In the third aim we will seek to extend these findings to dogs with hemophilia and inhibitors, and in the fourth aim we will assess the immunogenicity of these findings to dogs with hemophilia and inhibitors, and in the fourth aim we will assess the immunogenicity of the modified F.VII constructs used to generate fully processed F.VIIa as a secreted product. Successful completion of these pre-clinical studies should help to establish whether a gene-based approach to treatment of hemophilic inhibitors is feasible. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •
Project Title: GENE THERAPY OF BASAL FOREBRAIN CHOLINERGIC LESIONS Principal Investigator & Institution: Thal, Leon J.; Professor and Chair; Veterans Medical Research Fdn/San Diego Foundation of San Diego San Diego, Ca 92161 Timing: Fiscal Year 2001; Project Start 01-SEP-2000; Project End 31-AUG-2005 Summary: (adapted from applicant's abstract) Lesions of the cholinergic basal forebrain (CBF) system in animals using an immunotoxin produce robust behavioral deficits and mimic some aspects of Alzheimer's disease (AD). This model is useful for testing both the role of acetylcholine in cognitive processes and new therapeutic strategies such as gene therapy. The ability to control gene expression is an important requirement of this technology for clinical application. The vector systems being explored in this proposal may be exogenously regulated. This proposal will investigate mechanisms of restoring neurotransmitter function in animals with CBF immunotoxin lesions by 1) enhancing ACh release postgrafting via choline supplementation, and 2) transplanting cells capable of repressing or inducing the transgene for choline acetyltransferase (ChAT). The repressible system (tetracycline), and the inducible system (eccdysteroid), modulates gene expression of ChAT in a rapid, reversible and highly specific fashion. In the first series of experiments, the investigators will determine whether different doses of
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Doxycycline
exogenously administered choline can augment the production and release of acetylcholine from genetically engineered fibroblasts grafted to the cortex and hippocampus of rats following immunotoxic lesions of the CBF. Once an increase in release has been determined, behavioral effects of this augmented release will be determined. For the second and third series of experiments, they will use the regulatable cell lines that either induce or repress ChAT expression after administration of doxycycline or Muristerone A, respectively. In their immunotoxin lesion they will demonstrate that acetylcholine released from these cells after grafting to the neocortex and hippocampus is both necessary and sufficient for behavioral recovery. The effects of these regulatable genes will be tested in a spatial and non-spatial task after determining the dose and duration of the exogenous compound needed to induce or repress gene expression. If successful, the experiments will demonstrate that release of ACh can be exogenously controlled in animals and results in significant behavioral improvement. The control of transmitter release is necessary before grafting or direct gene insertion experiments can be entertained in humans in order to be able to safely terminate delivery of the gene product. These approaches will not only be applicable for AD, but other neurodegenerative disorders and for delivering other transgenes of interest. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •
Project Title: GENETIC PARTURITION
ANALYSIS
OF
MYOMETRIAL
FUNCTION
IN
Principal Investigator & Institution: Bethin, Kathleen; Pediatrics; Washington University Lindell and Skinker Blvd St. Louis, Mo 63130 Timing: Fiscal Year 2001; Project Start 01-MAY-2001; Project End 30-APR-2005 Summary: (Adapted from applicant's description): Despite advances in modem medicine, preterm labor continues to complicate 7-10% of all pregnancies. Infants delivered prematurely account for 85% of all perinatal mortality and morbidity. Clearly, an intervention designed to delay or prevent premature labor would be of great benefit. In order to study factors that effect parturition, we will develop a system that allows manipulation of uterine myometrial genes in the mouse. Using the reverse tetracycline trans-activator system, specific genes can be selectively expressed in the presence of doxycycline at chosen times during pregnancy. To begin to utilize this system to explore the roles of cAMP and oxytocin receptor in myometrial quiescence and contractility, respectively, this proposal seeks to fuse the tetracycline transactivator to smooth muscle promoters. The role of cAMP in relaxation in non-uterine smooth muscle has been welldocumented. Furthermore, beta- adrenergic agonists, which act by increasing cAMP levels, are widely used as tocolytic agents. The reverse tetracycline trans-activator system fused with a smooth muscle specific promoter will be used to over-express phosphodiesterase in uterine myometrium and study the effects of decreased myometrial cAMP on parturition in a mouse model. The results of these studies will help elucidate the parturition cascade in both term and preterm labor. In the future, this system will be used to study factors involved in stimulation of myometrial contraction rather than maintenance of uterine quiescence. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •
Project Title: GENETIC MANIPULATION OF AGE DEPENDENT TRAITS IN TRANSGENIC MICE EXPRESSING APP Principal Investigator & Institution: Ashe, Karen H.; Professor; University of Minnesota Twin Cities 200 Oak Street Se Minneapolis, Mn 554552070
Studies
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Timing: Fiscal Year 2001 Summary: The proposed studies address temporal relationships of behavioral and neuropathological dysfunction in transgenic (Tg) mice expressing the amyloid precursor protein (APP) in different genetic settings. Different host strains influence the type and onset of behavioral abnormalities, the type and extent of neuropathology, and the longevity of Tg APP mice, reflecting genetic variation between host strains that provides a rick source of information about genes that modify the phenotype of Tg mice expressing APP. However, these same strain related differences introduce experimental variability that could potentially thwart the reproducibility of scientific results. Identifying temporal windows of reversibility of phenotypic changes associated with expression of APP transgenes in mice may provide information about optimal timing of potential treatments. One interesting question about Alzheimer's disease (AD), particularly dominantly inherited AD, is why individuals at-risk remain neurologically well until many decades after birth. Two alternative hypotheses will be explored in Tg mice. First, we propose to identify an inbred strain of mouse in which to harbor a large APP transgene array. We will produce "speed congenics" using marker-assisted selection to produce the same level of congenicity at the fourth (N4) or fifth (N5) generation that normally takes 10 or 11 backcrosses. In an appropriate inbred strain, we will perform at closely spaced time intervals analysis of memory and learning, histopathology, and Abeta levels to asess the temporal inter-relationship of these traits. Second, we propose to test the hypothesis that amyloid deposits and/or deficits in learning and memory can be reversed by down-regulating expression of APP transgenes in adult mice. This shall be accomplished by developing a new type of Tg mouse harboring regulable APP transgenes using a tet-transactivator. Feeding mice doxycycline to suppress APP transgene expression at different times after the development of neuropathology of behavioral deficits will provide information about critical time windows allowing for reversibility of specific traits. Third, we propose to test the alternative hypothesis that delayed manifestation of disease traits in Tg2576 mice is caused either by chronicity of exposure or by an age-related biological change in the animal's ability to tolerate one or more toxic products involved with Tg APP expression. This shall be accomplished by developing Tg mice harboring regulable APP transgenes using a "reverse" tet-transactivator to study of the role of aging in AD. Feeding mice doxycycline to activate APP transgenes in mature or aging mice may allow us to distinguish between chronicity of exposure and a biological change in vulnerability related to aging. The observation that behavior and/or pathological traits ensure very shortly after activation in aging mice would favor the latter hypothesis. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •
Project Title: GM-CSF & ALVEOLAR MACROPHAGE ANTIVIRAL LUNG DEFENSE Principal Investigator & Institution: Trapnell, Bruce C.; Children's Hospital Med Ctr (Cincinnati) 3333 Burnet Ave Cincinnati, Oh 45229 Timing: Fiscal Year 2001; Project Start 01-AUG-2001; Project End 31-JUL-2005 Summary: This application will test the hypothesis that granulocyte-macrophage-colony stimulating alveolar macrophage (AM) innate antiviral mechanisms and by limiting inflammation during viral lung infection. GM is a hematopoietic growth factor recently shown to be vital to lung homeostasis and host defense. The role of GM in early hematopoiesis appears to be redundant, however, its role in the lung is unique. While the mechanism(s) through which GM regulates lung host defense are unclear, GM modulates multiple, diverse function of AM. Based on our preliminary data and
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Doxycycline
published reports, we propose that GM interacts with AM precursors in the lung, stimulating their terminal differentiation, and increases their capacity to internalize and degrade viral pathogens from the respiratory surface (i.e., GM increases intrinsic clearance of AM (ICAM). By increasing ICAM, GM increases primary pathogen clearance (i.e., by resident AM) thus reducing or obviating the need for chemotactic/proinflammatory cytokine signaling and secondary clearance (i.e., by recruited leukocytes). Murine models will be used in which the synthesis of GM is: 1) normal (GM+/+; 2) absent (GM-/-); 3) constitutively over- expressed in the lung (SPCGM/GM-/-); or 4) conditionally expressed in the lung under positive external control using a novel bitransgenic system (BTx-GM or BTx-GM/GM-/-. In the latter model, GM expression can be induced or extinguished, temporally, by addition or withdrawal of oral, aqueous doxycycline resulting in lung GM levels ranging from absence to overexpression. GM-deficient and replete mice will be used to study the in vivo role of GM in: (Aim 1) stimulating AM receptor expression and internalization of adenovirus; (Aim 2) trafficking and degradation of adenovirus in AM; and (Aim 3) limitation of inflammation during adenovirus infection of the respiratory tract. We will identify and characterize the mechanisms by which AM internalize and degrade adenovirus in vivo and in vitro. We will also discern the temporal relationship between GM expression in the lung and AM differentiation, ICAM (for adeno-virus), and the relationship between ICAM and limitation of lung inflammation. Our studies will help clarify the critical role of GM in modulating AM function, stimulation of innate lung host defense, and in limitation of lung inflammation and thus, will help establish the feasibility of the therapeutic use of recombinant GM for prevention or treatment of common acute and chronic lung infection and lung inflammation in various clinical disorders. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •
Project Title: HOST MODULATION/PERIODONTAL THERAPY EFFECTS ON DIABETES Principal Investigator & Institution: Ryan, Maria E.; Assistant Professor; Oral Biology and Pathology; State University New York Stony Brook Stony Brook, Ny 11794 Timing: Fiscal Year 2001; Project Start 30-SEP-2001; Project End 31-AUG-2003 Summary: (provided by applicant): Of the approximately 16 million Americans suffering from diabetes mellitus, about 10 percent have Type 1 diabetes. The complication of this chronic disease, i.e. nephropathy, retinopathy, neuropathy, angiopathy, impaired wound healing and periodontitis, significantly, impact the diabetic individuals quality of life. In recent years new adjunctive treatments, to classic insulin therapy, targeting factors know to play a role in these long-term complications have been developed and are being tested clinically. Diabetics tend to have an exaggerated host response to local microbial factors resulting in unusually destructive periodontal breakdown. In addition, periodontal infections resulting in excessive production of cytokines (1L1, 1L-6 and TNF (a)) induce insulin resistance and decrease insulin action. Tetracycline's, including a sub-antimicrobial dose of doxycycline (SDD), by virtue of non-antimicrobial properties can reduce level of these cytokines and other factors (matrix metalloproteinase {MMPs}), nitric oxide [NO]) known to play a role in diabetic complications, including periodontitis. These biological properties make SDD a compelling candidate for use in diabetics with periodontitis. Therefore, the objective of this research is to investigate the therapeutic potential of SDD in diabetic complications, such as periodontitis. The hypothesis of this proposal is that adjunctive periodontal therapy with SDD (compared to placebo) can improve clinical and local biochemical parameters of periodontitis as well as systemic biochemical and physiological
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parameters indicative of the likelihood of he progression or severity of long-term complications of diabetes. Accordingly, the specific aim of this proposal is to use a 9 month double -blind, placebo-controlled trail of Type 1 diabetics to determine the effect of SDD on: a) the clinical efficacy of non-surgical periodontal therapy; b) the oral microflora; c) oral, serum and urine levels of cytokines (1L-1, 1L6, TNF (a)), MMPs and NO; d) hemoglobin Aic, serum non-fasting glucose and fructosamine; and e) microalbuminuria and proteinuria. It is postulated that SDD, developed initially for the improved management of periodontitis, may be potential adjunct to insulin therapy in diabetic patients for the improved overall management of diabetes. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •
Project Title: HUMAN TISSUE FACTOR AND ITS PLASMA INHIBITOR Principal Investigator & Institution: Broze, George J.; Professor; Barnes-Jewish Hospital Ms 90-94-212 St. Louis, Mo 63110 Timing: Fiscal Year 2001; Project Start 01-JUL-1988; Project End 30-JUN-2003 Summary: (Investigator's abstract) Tissue factor pathway inhibitor (TFPI) is a critical regulator of tissue factor induced coagulation. The overall goals of this proposal are to further delineate the structures within the TFPI molecule that mediate its specific functional properties and to better define the physiologic role of TFPI through the use of mouse models. The specific aims are: 1) determine the structure of 34 kDa TFPI bound in plasma by low density lipoproteins (LDL) and determine the mechanisms underlying this association; 2) investigate the mechanisms of TFPI association with cell surfaces by examining the structure and properties of a mammalian expressed rTFPI which lacks this attribute; 3) further characterize TFPIK1 gene-disrupted mice which have an isolated deficiency in TFPI-mediated factor VIIa/TF inhibition; 4) produce TFPI null mice and compare their phenotype with that of TFPIK1 mice; and 5) attempt to rescue TFPIK1 (-/-) mice from intrauterine mortality with doxycycline-regulated transgene expression of TFPI to permit the evaluation of the physiologic role of TFPI in adult animals. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen
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Project Title: INDUCIBLE DOMINANT NEGATIVE OF STAT 6 IN MEMORY IGE Principal Investigator & Institution: Miller, Rachel L.; Medicine; Columbia University Health Sciences New York, Ny 10032 Timing: Fiscal Year 2001; Project Start 01-AUG-1998; Project End 31-JUL-2003 Summary: (Adapted from applicants' abstract) The cross-linking of immunoglobulin E (IgE) bound to high affinity Fc receptors on the surface of mast cells or basophils triggers much of the inflammatory responses and symptomatology in allergic reactions and extrinsic asthma. The cytokine interleukin 4 (IL-4) mediates primary IgE responses by inducing class switching to IgE, via the transcription factor Stat6. The binding of IL-4 to its receptor on B cells initiates the dimerization, activation, and nuclear translocation of Stat6 so that it binds to IL-4 response elements in the promoter of IL-4 inducible genes. Germline E transcription follows and permits deletional recombination upstream of the heavy chains that encode for IgE. Knockout models have confirmed in vivo that primary IgE class switching depends upon the activation of the transcription factor Stat6. However, the mechanism for IL-4-mediated secondary or memory IgE remains obscured. Understanding this mechanism is important to comprehending the pathophysiology of human clinical allergic disease because it is characterized by repeated exposures to allergens, resulting in even greater IgE production. The overall
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Doxycycline
aim is to determine whether or not the role of IL-4 signaling though Stat6 is an established or memory IgE allergic immune response. The applicant proposes to develop an inducible dominant negative system in order to study the importance of Stat6 the memory IgE response. Dominant negative Stat6 molecules will be generated by either a carboxy terminus truncated Stat6 mutant molecule or a chimeric Stat6/KRAB protein each possessing the hCMV regulatory minimal promoter with upstream tetoperators regulated by the rtTA-encoding gene that becomes activated in the presence of doxycycline. The efficacy of the system will be evaluated in vitro and in vivo in transgenic mice and employed to determine if the expression and induction of dominant negative Stat6 can alter a secondary IgE response. Both the memory allergic response to antigenic stimulation and the polyclonal IgE response will be studied. In addition, the components of the memory response that are affected by Stat6 activity will be analyzed. (End of Abstract) Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •
Project Title: INDUCIBLE GENE EXPRESSION IN MOUSE UROTHELIUM Principal Investigator & Institution: Reeder, Jay E.; Pathology and Lab Medicine; University of Rochester Orpa - Rc Box 270140 Rochester, Ny 14627 Timing: Fiscal Year 2003; Project Start 01-AUG-2003; Project End 01-JUL-2005 Summary: (provided by applicant): The primary research objective of this proposal is the development of an experimental system for the temporal and tissue-specific control of gene expression in the mouse urothelium. The model system will be validated by demonstration of controlled expression of the erbB2 oncogene. The tetracycline control system will be used in a bi-transgenic strategy. One of the two transgenic mouse strains TRE-erbB2 has been used to show erbB2 dependent hyperplasia of epithelial tissues. This mouse strain is available for these studies. The second transgenic mouse strain will have the reverse tetracycline transactivator (rtTA) gene under control of the uroplakin II (UPII) promoter for urothelium specific expression. In crosses between the TRE-erbB2 and UPII-rtTA mice the rtTA protein will be used to up regulate transcription of the TRE-erbB2 transgene in the presence of the tetracycline related antibiotic, doxycycline. In this way the expression of the erbB2 oncogene will be tissue specific and regulated in time by administration of doxycycline in drinking water. Each of the component parts of this system have been validated independently and will be assembled together here as a valuable tool for the investigation of urothelial growth, differentiation, and tumorigenesis. The UPII-rtTA transgenic mouse may also be crossed to control other genes placed under control of the TRE. The specific aims of this application are: Specific aim 1:Characterize UPII-rtTA transgenic mice and establish homozygous lines. Specific Aim 2: Determine the impact on mouse urothelium of doxycycline exposure in UPIIrtTA and TRE-erbB2 transgenic mice. Specific aim 3: Determine the impact of activated erbB2 expression on cellular proliferation and tumorigenesis in the mouse urothelium. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen
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Project Title: INDUCIBLE GENE EXPRESSION IN RETINAL GANGLION CELLS Principal Investigator & Institution: Kerrison, John B.; Assistant Professor; Ophthalmology; Johns Hopkins University 3400 N Charles St Baltimore, Md 21218 Timing: Fiscal Year 2002; Project Start 30-SEP-2002; Project End 29-SEP-2007 Summary: (Applicant's Abstract) This proposal outlines a clinician-scientist training program in molecular biology, which includes didactic course work and laboratory investigation. It will be conducted under the supervision of an experienced mentor in a
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supportive research environment with the ultimate goal of transitioning the applicant to an independent physician/research. The broad objective of the applicant is to better understand the molecular basis of retinal development, particularly retinal ganglion cell determination and differentiation. The ultimate goal is to assimilate this information into an integrated understanding of retinal development that may advance future transplantation and/or regeneration therapies for retinal and optic nerve disease. The proposed research plan endeavors to develop an inducible system for retinal ganglion cell specific expression in order to further characterize retinal transcription factors and their networks in vivo with the use of microarray analysis. The initial specific aim of the project is to develop a doxycycline mediated system for in vivo retinal ganglion cell specific gene expression in transgenic mice. This system permits the control of both the timing and dosage of gene expression by the administration of doxycycline in drinking water. The second specific aim is to use this system to induce the expression of the POU domain containing retinal ganglion cell development as evidenced by a 70% reduction in retinal ganglion cell number in Brn3b knockout mice. The final specific aim is to ascertain the network of genes regulated by Brn3b using microarrays. Microarray analysis, which offers an opportunity to identify and quantify the simultaneous expression of a large number of genes, is well suited for the identification of those genes that are up-regulated or down-regulated by a particular transcription factor under various conditions. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •
Project Title: INDUCIBLE LIF RECEPTOR ABLATION IN ADULT MICE Principal Investigator & Institution: Ware, Carol B.; Comparative Medicine; University of Washington Seattle, Wa 98195 Timing: Fiscal Year 2001; Project Start 01-JUL-2001; Project End 30-JUN-2004 Summary: The ability to selectively, inducibly and reversibly target mutations to specific proteins in adult mice would be a powerful tool in the study of aging. Toward this goal, we have made a tetracycline responsive ablation of the gene for the leukemia inhibitory factor receptor (LIFR) in ES cells. This mutation has transmitted through the mouse germline and mating pairs heterozygous for the targeted mutation are now producing pups. Loss of LIFR using standard non-inducible gene targeting techniques is a perinatal lethal profoundly affecting many systems including bone (osteoporosis) and glial cell development (agliogenesis). Thus, we are now poised to address: 1. the utility of a tetracycline inducible gene ablation approach in the study of aging 2. identification of adult consequences of LIFR loss. The inducible targeting vector incorporates a complete set of tet-off elements so that a full length rat LIFR cDNA is incorporated homologously into exon 2 of the mouse LIFR effectively ablating the mouse gene with tetracycline control of the introduced rat LIFR homolog. Because rat LIFR insertion is targeted to be under appropriate control of the endogenous mouse LIFR promoter elements, expression of rat LIFR is on where murine LIFR is constitutively expressed in the absence of a tetracycline derivative, doxycycline (Dox) and silenced in the presence of Dox. Expression of rat LIFR is reactivated upon removal of Dox. Sensitivity of this system will be studied both by semi- quantitative reverse transcription polymerase chain reaction (rtPCR) to measure whole tissue alterations in LIFR levels in response to Dox in the drinking water and by utilizing a beta-galactosidase reporter gene incorporated in the targeting construct which is also switched off in the presence of Dox. Beta-galactosidase will be visualized in situ by X-gal staining to analyze localized effects of Dox administration. Effects of Dox and preliminary analysis of biological consequences of adult LIFR ablation will be assessed in bone, the central nervous
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system, skeletal and cardiac muscle, lung, liver, pancreas, spleen and kidney. In summary, a new technique for adult genetic manipulation will be developed and characterized that will elucidate the role in aging of the multi-functional cytokines that utilize LIFR. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •
Project Title: INDUCING BONE FORMATION--LOW DOSE DOXYCYCLINE FOR POSTMEN Principal Investigator & Institution: Gruber, Barry; State University New York Stony Brook Stony Brook, Ny 11794 Timing: Fiscal Year 2001 Summary: Osteoporosis is a prevalent disease with widespread devastating clinical consequences. Treatment to date has involved agents which by and large prevent bone loss rather than induce new bone formation; thus we have obvious limitations in treatment options for the patient with established disease. No safe effective bone forming agent has yet to be approved for the treatment of this disease. The purpose of this study is to test the safety and efficacy of Low Dose Doxycycline for stimulation of bone formation in postmenopausal women with osteoporosis. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen
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Project Title: INNATE IMMUNE RESPONSES IN LYMPHATIC FILARIASIS Principal Investigator & Institution: Hise, Amy G.; Medicine; Case Western Reserve University 10900 Euclid Ave Cleveland, Oh 44106 Timing: Fiscal Year 2003; Project Start 01-SEP-2003; Project End 31-AUG-2008 Summary: (provided by applicant): The research goal of this application is to initiate studies to identify specific innate immune receptors, including toll-like receptors (tlr) that are activated by filarial and Wolbachia products. Additionally, early immune effector molecules involved in the inflammatory response, such as cytokines and chemokines, will be identified. Initial laboratory studies will utilize transfected cell lines and animal models to identify important receptor pathways. Later work will confirm the mechanism of recognition and response to filarial and Wolbachia products in human disease using peripheral blood monocytes from humans infected with Wuchereria bancrofti in Papua New Guinea. Training in laboratory techniques, research methodology and ethics, field based research and clinical tropical medicine will be important components of the project. Wolbachia are obligatory intracellular bacteria that infect all filarial species of medical significance. Recent observations indicate that lipopolysaccharide (LPS)-Iike products of Wolbachia endosymbionts induce acute inflammatory responses in the mammalian host. Preliminary studies using CD14+ monocytes from filadae-naive humans indicate that B. malayi extracts stimulate TNFalpha, IL-6, and IL-10 production. In contrast, Acanthocheilonema viteae, a filarial parasite not infected with Wolbachia, or B. malayi treated with doxycycline stimulate little to no cytokine production by monocytes. Experiments using transfected cell lines expressing human toll-like receptors and monocytes exposed to B. malayi extracts with competitive inhibitors of the LPS - TLR4 interaction suggest that the stimulatory effects of Brugia are exerted through both TLR4 and TLR4-independent pathways. However, differences and similarities of receptors involved in recognition of nematode versus Wolbachia ligands have not yet been identified. The aims of this project are to identify specific innate immune receptors including the toll-like receptor family and signaling pathways that are activated by filarial and Wolbachia products and to characterize the
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early innate immune mechanisms by which the human host recognizes and responds to filarial infections including those mediated by endosymbiotic Wolbachia. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •
Project Title: INPATIENT VS OUTPATIENT THERAPY FOR ACUTE PELVIC INFLAMMATORY DISEASE Principal Investigator & Institution: Holley, Robert L.; University of Alabama at Birmingham Uab Station Birmingham, Al 35294 Timing: Fiscal Year 2001 Summary: Pelvic inflamatory disease (PID) affects women in the United States in nearepidemic proportions. Nearly 11% of American women of reproductive age reported that they received treatment for PID in 1988. The costs associated with PID and its sequelae are enormous. Annual U.S. expenditures for the acute treatment of PID have been estimated at between $700 million and $2 billion annually; indirect costs may amount to an additional $1 billion per year. Inpatient treatment is over 10 times more expensive than outpatient treatment. The primary aim of thi study is to test the effectiveness and cost-effectiveness of outpatient vs. inpatient treatment for PID in preventing involuntary infertility. Additional long-term outcomes to be compared are repeat episodes of PID, ectopic pregnancy, functional decline due to chronic pelvic pain, frequency of health service use, the occurrence of indirect costs associated with PIDrelated illness, and patient-reported quality of life. This study is a randomized clinical trial involving adult female patients. During a 5-year period, 1,380 women will be enrolled from 6 clinical sites. A total of 1,200 women in seven clinical sites will be randomized in equal numbers into one of two treatment groups: inpatient or outpatient. Non-investigational antibiotics consisting of Cefoxitin and Doxycycline will be used in both groups, with a total treatment course of 14 days. Follow-up for each patient encompasses a period of 60 months. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen
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Project Title: KNOCK-IN MODEL FOR INNER EAR HAIR CELL REGENERATION Principal Investigator & Institution: Barald, Kate F.; Associate Professor; Cell and Developmental Biology; University of Michigan at Ann Arbor 3003 South State, Room 1040 Ann Arbor, Mi 481091274 Timing: Fiscal Year 2002; Project Start 01-JUL-2002; Project End 30-JUN-2007 Summary: (provided by applicant): Sensory hair cell (HC) loss is a major cause of human deafness, tinnitis and balance disorders. However, despite great progress in many laboratories, the molecular bases for both hair cell development and regeneration are still not understood. We propose to test the novel hypothesis that mammalian hair cell regeneration in vivo will be possible if we can induce HCs to re-express the critically important growth factor Bone Morphogenetic Protein 4 (BMP4). In the experiments proposed here, we will make a transgenic "knock-in" mouse, in which BIVIP4 can be expressed in mammalian hair cells under a dual control system. We will engineer constructs that place a full-length BMP4 under the control of the hair-cell specific brn3.1 promoter, in a tet-on inducible system, so that providing the transgenic mice with doxycycline (DOX) will turn on BMP4 expression specifically in terminally differentiated hair cells of the inner ear that normally do not express BIVIP4. BIVIP4 is an axial patterning morphogen, but more significantly, it is a major "plasticity" gene that keeps sensory and neuronal cells in a proliferative state, resembling stem cells. We will first express this tet-on construct in immortalized inner ear cell lines derived from day 9
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Immortomouse otocysts and in mouse embryonic stem cells (ES) in culture. We have made constructs that drive luciferase, to test the proof of principle. We can also compare the genetic expression repertoire of the cells induced with DOX to those of cells that are not induced by RT-PCR and by gene array techniques. Next we will make a transgenic knock-in mouse that is capable of re-expressing BMP4 in all of the hair cells of the inner ear. We will study the cellular morphology and HC repair and regenerative capacity of these mice in the presence and absence of DOX; that is, when the hair cells are either capable of re-expressing BIVIP4 or not. We are testing the hypothesis that if BIVIP4 is reexpressed in hair cells of the inner ear, returning these cells to an earlier more 11 stem cell-like" state, we will be able to regenerate a sensory epithelium after either noiseinduced trauma or ototoxic aminoglycoside exposure. By using focal noise exposure or precisely dosed and delivered aminoglycosides, we can vary the site and extent of the lesions, and determine the degree to which repair, regeneration and/or preservation play a role in restoring a functional sensory epithelium. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •
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 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
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Project Title: LOW-DOSE DOXYCYCLINE EFFECTS ON OSTEOPENIC BONE LOSS Principal Investigator & Institution: Payne, Jeffrey B.; Professor and Assistant Dean for Researc; Surgical Specialties; University of Nebraska Medical Center Omaha, Ne 681987835 Timing: Fiscal Year 2001; Project Start 01-JUL-2001; Project End 30-JUN-2006 Summary: Osteoporosis represents a major public health problem in the United States. Osteoporosis is associated with decreased systemic bone mineral density (BMD), an increased incidence of vertebrae, wrist and hip fractures, and tooth loss. The dominant pathogenic factor for osteoporosis in postmenopausal women is estrogen (E2) deficiency. In longitudinal NIH-supported clinical trials, we have shown accelerated
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alveolar crestal bone height and density loss in postmenopausal, E2- deficient women with a periodontitis history relative to E2-sufficient women, and in osteoporotic/osteopenic women versus women with normal lumbar spine BMD. Because of this relationship between E2- deficiency, osteoporosis and oral bone loss, it is desirable to test therapeutic strategies to mitigate alveolar bone loss in postmenopausal women. A recent discovery by Dr. Golub (Co-PI) showed that tetracyclines, including low-dose doxycycline (LDD), by virtue of a non- antimicrobial property, can: a) inhibit host-derived, tissue-destructive matrix metalloproteinases (MMPs), including collagenases, involved in bone resorption; and b) stimulate osteoblast activity and bone formation. These biological properties make tetracyclines compelling candidates for use in postmenopausal women with periodontitis. Therefore, the objective of this research is to investigate the therapeutic potential of LDD in postmenopausal osteopenia and periodontitis, diseases characterized by excess collagen breakdown and bone resorption. The hypothesis of this proposal is that LDD (compared to placebo) can improve radiographic, clinical and biochemical parameters of periodontitis in E2-deficient, osteopenic postmenopausal women with periodontitis. Accordingly, the specific aim of this proposal is to use a 2- year double-blind, placebo-controlled trial of E2-deficient women to determine the effect of LDD on: a) alveolar bone crestal and subcrestal density (measured by computer-assisted densitometric image analysis) and linear alveolar crestal bone height; b) clinical periodontal measurements such as probing depth and relative clinical attachment level; and c) gingival crevicular fluid markers of bone turnover (e.g., C- terminal telopeptide pyridinoline crosslinks [ICTP, a collagen breakdown fragment]). As a secondary aim, the study will evaluate the effect of LDD on systemic bone mineral density at the lumbar spine and femoral neck by dual-energy xray absorptiometry (DEXA) and the effect of LDD on serum and urine biochemical markers of bone turnover. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •
Project Title: LYMPHOTOXIN--REGULATION AND BIOLOGIC SIGNIFICANCE Principal Investigator & Institution: Ruddle, Nancy H.; Professor; Epidemiology and Public Health; Yale University 47 College Street, Suite 203 New Haven, Ct 065208047 Timing: Fiscal Year 2001; Project Start 01-JAN-1978; Project End 31-MAR-2002 Summary: (Adapted from the Investigator's abstract): The goals of this project are the delineation of the biological roles and molecular regulation of lymphotoxin (LT; LT alpha; TNF beta) as an entity in itself and with regard to its relationship to the other members of the LT/TNF family, tumor necrosis factor (TNF alpha) and LT beta. LT alpha can assume two molecular forms: a secreted homotrimer, or a cell-associated heterotrimeric LT alpha/beta complex. LT alpha has been implicated in the pathogenesis of autoimmune diseases and participates in defense against cancer through its ability to kill cells by apoptosis and promote inflammation. Mice genetically deficient in LT alpha have no lymph nodes or Peyer's patches and exhibit splenic disorganization indicating a crucial role in lymphoid organ development. Mice transgenic for LT alpha under the control of the insulin promoter (RIPLT) exhibit inflammation at the sites of transgene expression. This inflammation has most of the characteristics or organized lymphoid tissue, suggesting that LT-induced chronic inflammation is lymphoid neogenesis. The RIPLT transgene restores LN but not splenic architecture to LT alpha -/- mice. The specific aims are to: 1) Determine whether LT beta contributes to lymphoid organ development; 2) Identify the temporal limits and physical forms by which ectopic LT restores lymphoid organs; 3) Identify the mechanisms by which LT induces lymphoid organogenesis; 4) Determine which cells
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produce LT alpha in development and define the molecular basis of its regulation. These aims will be accomplished by analyzing LT beta -/- mice; by studying the reconstitution of LN in RIPLT.LT alpha -/- mice and in a new LTtet inducible system; by analyzing LT's effects in reconstituted RIPLT.LT alpha -/- and doxycycline induced tetLT.LT alpha -/- mice on adhesion molecules, chemokines, and dendritic cells; and analyzing developmentally regulated LT expression in mice transgenic for LT alpha regulatory regions driving expression of human CD8 alpha or beta-galactosidase reporter genes. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •
Project Title: MAMMARY SUSCEPTIBILITY
DEVELOPMENT
AND
BREAST
CANCER
Principal Investigator & Institution: Chodosh, Lewis A.; Associate Professor; Medicine; University of Pennsylvania 3451 Walnut Street Philadelphia, Pa 19104 Timing: Fiscal Year 2001; Project Start 17-JUL-2001; Project End 30-JUN-2006 Summary: (provided by applicant) Epidemiologic and animal studies strongly suggest that the susceptibility of the mammary gland to carcinogenesis is a function of the gland's developmental state at the time of exposure to oncogenic stimuli. Specifically, reproductive endocrine events such as puberty, pregnancy, and parity have each been shown to markedly influence the susceptibility of the mammary gland to the subsequent development of cancer. At present, the cellular and molecular mechanisms by which normal developmental events modulate breast cancer risk are essentially unknown. Understanding these mechanisms is a central goal of our laboratory and will undoubtedly require a more complete understanding of the interaction between mammary development, reproductive history, and oncogenic pathways than currently exists. The central hypothesis of this proposal is that the susceptibility of the mammary gland to oncogene-induced carcinogenesis is a function of the specific developmental context in which oncogene activation occurs. Specifically, we hypothesize that normal developmental events such as puberty, pregnancy and parity modulate breast cancer susceptibility by modulating the effects of oncogenic stimuli on proliferation, differentiation, apoptosis, and global patterns of gene expression. In order to test this hypothesis, we have generated a novel doxycycline-dependent bitransgenic mouse model system that permits oncogenes to be inducibly expressed in the mammary epithelium for a defined period of time, at a desired level, and during any desired developmental stage. Iransgene expression in this system is mammary-specific, can be titrated over a wide range of expression levels, and is essentially undetectable in the uninduced state. Inducible expression of the c-MYC proto-oncogene using this system results in the formation of invasive mammary adenocarcinomas in a manner that is rapid, highly penetrant, mammary-specific, and absolutely dependent on transgene induction by doxycycline. These properties make this system ideally suited for expressing oncogenes in a spatially and temporally restricted manner during defined stages of development. In the present application we will use this inducible transgenic system to deliver distinct oncogenic stimuli during defined windows in development in order to test our hypothesis that normal developmental events modulate breast cancer susceptibility by modulating oncogene action. The experiments proposed will generate and validate four inducible transgenic mouse models for mammary tumorigenesis based on oncogenic pathways that are relevant to human breast cancer. These transgenic models will be used to determine the susceptibility of the mammary gland to oncogenemediated carcinogenesis as a function of developmental stage, as well as to investigate the cellular mechanisms by which developmental events influence oncogene action. We
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anticipate that these studies will help to illuminate developmental mechanisms that contribute to the determination of breast cancer susceptibility. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •
Project Title: MECHANISM(S) OF MACROPHAGE-MEDIATED DEMYELINATION Principal Investigator & Institution: Hentati, Afif; Evanston Northwestern Healthcare 2650 Ridge Ave Evanston, Il 60201 Timing: Fiscal Year 2002; Project Start 01-FEB-2002; Project End 31-JAN-2007 Summary: (provided by applicant): The applicant is now finishing his residency training in Neurology. Prior to this residency, he was involved in basic research and gained significant experience in molecular genetics. He made several contributions to research of genetic causes of motor neuron disease and related disorders. He is changing his main research focus to multiple sclerosis (MS), and proposes to develop transgenic mouse model for MS with doxycycline-controllable expression of interleukin-3 (IL-3) in astrocyte. The proposal is based on the previous observation that constitutive overexpression of IL-3 in astrocytes of GFAP-IL3 transgenic mice causes microglia/macrophage-mediated demyelination that resembles MS. The control of IL-3 expression will permit to overcome several limitations of GFAP-IL3, including toxicity of IL-3 to developing brain and allow the analysis of various conditions of expression of the transgene. The candidate will analyze clinical and pathologic aspects of the disease with varying levels of expression and host-age at initial induction of IL-3. Progression patterns after discontinuation of IL-3 expression in symptomatic mice will be analyzed. Analysis of cytokine and chemokines expression by RNase protection assay, and of gene expression by gene microchips assay will determine the molecular cascade (s) involved in demyelination. These findings may be relevant to MS. The candidate will dedicate 75% of his time to research and 25% to clinical activity. He will be developing his skills in immunology and will be working closely with Dr. Lipton who has extensive experience in experimental animal models of demyelination. The candidate's long-term plan is to establish an independent research program focused on the development of genetic animal models for MS and the study of the role of macrophage and microglia in the genesis and the progression of CNS demyelination. 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 2001; 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 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
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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: MODEL SYSTEMS FOR THE STUDY OF FRAGILE X SYNDROMEN Principal Investigator & Institution: Warren, Stephen T.; William Patterson Timmie Professor and c; Emory University 1784 North Decatur Road Atlanta, Ga 30322 Timing: Fiscal Year 2001; Project Start 10-SEP-1997; Project End 30-JUN-2006 Summary: The fragile X syndrome is due to the absence of the FMR1 protein, FMRP. A mouse Finn knockout exhibits cognitive deficiencies and macroorchidism, recapitulating features of the human syndrome. Despite advances in our understanding of FMRP function and the consequence of its absence, many simple, yet fundamental questions remain elusive. A critical need throughout the entire gamut of such research is the availability of mice and cultured cells where Fmrp levels are easily modulated. The PL proposes here the development of several such models. Several lines of mice engineered where the Fmrp levels can be regulated by doxycycline exposure will be developed These will range from the traditional transgenic animal with the tetracycline-response element (TRE) promoter driving the Fmr1 cDNA on a knockout background to more sophisticated approaches. One novel approach maintains normal alternative splicing variation and normal cell expression specificity by replacing, in embryonic stem cells, the normal mouse FMR1 promoter with a TRE without otherwise modifying the murine gene. Another novel approach will be the fusion of a HIV-TAT transducing domain with the CRE recombinase. Purified fusion protein can easily enter all cell types and delete the genomic interval between direct lox repeats. Using this approach the PL will develop the ability to selectively ablate FMR1 in discreet organs and brain regions. From all mouse models developed, immortalized cell lines will also be developed for experiments where cultured cells would be most appropriate. All models will be rigorously tested for parameters of inducible FMR1 expression and decay. Using these models the PL will test fundamental issues involving fragile X syndrome, ranging from biochemical and cell biological questions to determining if FMRP expression is essential during development or if later expression of FMRP can influence the cognitive deficit. Such data is of fundamental importance in the consideration of therapeutic interventions. Developing, testing, and utilizing these mice and cells derived from them
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should substantially advance the analysis and understanding of FMRP function and the consequences of its absence. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •
Project Title: MODULATION OF ERBB SIGNALING Principal Investigator & Institution: Wu, Jie; Associate Professor; H. Lee Moffitt Cancer Ctr & Research Ins and Research Institute, Inc. Tampa, Fl 336129497 Timing: Fiscal Year 2003; Project Start 01-JAN-1999; Project End 30-JUN-2008 Summary: (provided by applicant): The overall goals of this project are to elucidate regulatory mechanisms of ErbB signaling components and to explore these molecules as molecular targets for cancer therapy. SHP2 protein tyrosine phosphatase (PTPase) mediates ErbB-induced Erk mitogen-activated protein (MAP) kinase activation and is involved in cytoskeletal reorganization and cell motility. However, how SHP2 mediates these responses is not well understood. It has been shown that Gab1 is a key SHP2 regulator in epidermal growth factor (EGF)-stimulated cells and that Src and Ras are activated by SHP2, but the mechanisms by which SHP2 activates Src and Ras have not been defined. Two models for SHP2-mediated Src activation are postulated and will be evaluated in Specific Aim I. The involvement of Src in EGF-induced Ras and Erk activation also will be analyzed. In Specific Aim II, the novel small interfering RNA (siRNA) technique for gene knockdown will be developed and used to analyze the role of Gab1, Gab2, and SHP2 in EGF-induced cellular responses. These include Src and Akt/PKB activation, temporal regulation of Ras-MAP kinase activation, gene expression, paxillin dephosphorylation, and cell growth and metastatic properties. Based on our preliminary observations, we postulate that Gab1 and related pleckstrinhomology (PH) domains are novel molecular targets for antagonizing ErbB signaling and PTEN mutation in human cancers. This hypothesis will be evaluated in Specific Aim III using doxycycline-inducible decoy constructs in stable cancer cell lines in vitro and in tumor xenografts. These studies will define a major ErbB and SHP2 signaling mechanism, greatly advance our understanding of the function of Gab proteins, uncover novel targets for molecular intervention of malignant signaling, and stimulate further development of new inhibitors targeting these signaling components for cancer treatment. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen
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Project Title: MOLECULAR MECHANISMS OF ANEURYSMAL DEGENERATION Principal Investigator & Institution: Thompson, Robert W.; Professor; Surgery; Washington University Lindell and Skinker Blvd St. Louis, Mo 63130 Timing: Fiscal Year 2001; Project Start 01-AUG-1996; Project End 31-JUL-2005 Summary: (Adapted from Applicant's Abstract): Abdominal aortic aneurysms (AAAs) are a common degenerative disease with life-threatening implications. The purpose of this research program is to better understand the regulation of individual gene products within the aneurysmal aorta and their parthophysiologic implications in disease progression. A novel murine model of elastase-induced aortic injury has been developed that recapitulates many critical features of human AAA, including transmural infiltration of the aortic wall by mononuclear phagocytes, increased local production of matrix metalloproteinases (MMPs), and progressive degradation of aortic wall collagen and elastin. Using this model, it has been shown that mice with targeted gene disruption of MMP-9 exhibit a significant reduction in aneurysmal degeneration. It has also been shown that the treatment with doxycycline reduces aortic wall expression
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Doxycycline
of MMP-9 in patients undergoing elective AAA repair, and that doxycycline suppresses phorbol-stimulated expression of MMP-9 in cultured human THP-1 mononuclear phagocytes. These studies suggest that inflammatory cell production of MMP-9 plays a critical role in the process of aneurysmal degeneration and that treatment with doxycycline has the potential to repress mononuclear phagocyte expression of this enzyme. This project will extend these observations by identifying the critical molecular steps involved in elastase-induced aneurysmal degeneration in the mouse and by elucidating the molecular pathways by which aneurysmal degeneration might be suppressed by MMP-inhibiting tetracyclines. These goals will be accomplished through four specific aims: (1) determine if the generation of biologically-active elastin degradation peptides is responsible for leukocyte recruitment, aortic wall infiltration, and MMP expression during the initiation of elastase-induced AAA; (2) clarify the molecular mechanisms(s) by which targeted deletion of MMP-9 suppresses the development of elastase-induced AAA; (3) establish if urokinase-type plasminogen activator (u-PA) or additional MMPs are required in the development of elastaseinduced AAA; and (4) define the molecular mechanism(s) by which doxycycline suppresses PMA-stimulated expression in cultured human THP-1 mononuclear phagocytes, and determine if a reduction in MMP-9 expression can explain the protective effects of doxycycline in vivo. These investigations can be expected to add considerably to our understanding of the molecular mechanisms of aneurysmal degeneration, potentially forming the basis for new treatment strategies. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •
Project Title: NEUROPATHOGENIC MECHANISMS OF PRION STRAINS Principal Investigator & Institution: Dearmond, Stephen J.; University of California San Francisco 500 Parnassus Ave San Francisco, Ca 94122 Timing: Fiscal Year 2001 Summary: The overall aims are to gain a better understanding of the mechanisms of differential targeting of neurons by prion strains, a better understanding of the cellular and molecular mechanisms of nerve cell dysfunction, degeneration and death in prion diseases, and to test whether clearance of PrpSc from the brain corrects cellular defects and neuronal vacuolation and foster reactive synaptogenesis. Aim 1 tests a membrane hypothesis of pathogenesis that proposes theat the most fundamental cellular defects in prion diseases are an accumulation of abnormal PrP (PrP/Sc in scrapie and CJD and tm PrP in some GSS-like disease) in neuronal plasma membranes with a proportional change in the properties of the plasma membrane. We will correlate the degree of change in synaptosomal membrane fluidity, measured by electron spin resonance spectroscopy, with the concentration of PrPSc or tmPrP. In Aim 2 we will test the hypothesis proposed by others that dysfunction and possibly death of the parvalbumin subset of GABAergic neurons precedes grey matter vacuolation. An extensive stereological quantitative study of parvalbumin and GABA nerves cell bodies and synapse numbers as a function of PrPSc or tmPrP accumulation is proposed. Aim 3 proposes to use doxycycline-treated Tg(tTA:MoPrP) mice (Project 3) to directly test whether PrPSc accumulation in plasma membrane is the cause of neuronal dysfunction, specifically by testing the effect of clearance of PrPSc on plasma membrane properties, vacuolation, and parvalbumin neurons. We will also test whether clearance of PrPSc corrects decreased release of GABA from synaptosomes (see Progress Report) and allows reactive synaptogenesis to replace lost synapses. Aim 4 focuses on our hypothesis that the two Asn-linked PrP oligosaccharides influence host animal and prion-strain determined differential targeting of neurons. Specifically, we will examine a
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new transgenic mouse the effect on the disease phenotype. We will also test whether or not prion strain properties are influenced by the brain region from which they are derived by transmitting human vCJD derived from different brain regions to susceptible transgenic mice. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •
Project Title: NGF RECEPTOR REGULATION OF PROSTATE GROWTH Principal Investigator & Institution: Djakiew, Daniel; Professor; Cell Biology; Georgetown University Washington, Dc 20057 Timing: Fiscal Year 2001; Project Start 01-MAY-1999; Project End 30-APR-2003 Summary: Aberrant regulation of growth of the human prostate is responsible for much of the morbidity and mortality associated with BPH and other forms of prostatic neoplasia in the aging adult male population. In part, growth of the prostate is mediated by the paracrine/autocrine interaction between NGF and its cognate high affinity TrkA receptor and the low affinity NGF receptor (LNGFR). Hence, based upon our prior published work in conjunction with additional preliminary studies reported herein, we propose to test the hypothesis that the two types of NGF receptors, TrkA and the LNGFR stimulate and inhibit growth, respectively, in human prostate epithelial cells. Studies to support this hypothesis are proposed as three specific aims. The first specific aim is to characterize expression of the Trk family members, TrkA, TrkB and TrkC in the normal, BPH and neoplastic pathologic prostate by in situ hybridization and immunohistochemistry. Differential expression of these Trk family members will be correlated with the pathology of the prostate and a proliferating cell nuclear antigen (PCNA) proliferation index. In this manner, changes in the expression of the Trks may be related to the rate of growth and pathology of the prostate. The second specific aim will directly test the putative growth stimulatory effects of the TrkA receptor by transfection with a double stable Tet-On inducible expression system in which Doxycycline is used to regulate the level of TrkA overexpression in a prostate epithelial cell line. The induced overexpression of TrkA will be evaluated in relation to the rate of growth of these cells. The third specific aim will directly test the putative growth inhibitory effects of the LNGFR by transfection with a double stable Tet-On inducible expression system in which Doxycycline is used to regulate the level of LNGFR reexpression in a prostate epithelial cell line. The induced re-expression of the LNGFR will be evaluated for changes in the rate of growth of these cells as it pertains to proliferation and induction of programmed cell death. Our studies have already identified NGF receptors as targets for the clinical perturbation of prostate growth. As a result, phase I clinical trials are currently underway with an indolocarbazole Trk antagonist for the treatment of aberrant prostatic growth at Georgetown University Medical Center. A comprehensive investigation of the NGF receptors in the human prostate should be broadly applicable to our understanding of the mechanism of NGF mediated autocrine/paracrine regulation of prostate growth and hasten the translation of these observations to the clinical setting. 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.; Assistant Professor; 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
40
Doxycycline
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 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 RECEPTOR CO-ACTIVATORS IN THE LUNG Principal Investigator & Institution: Yan, Cong; Assistant Professor; Children's Hospital Med Ctr (Cincinnati) 3333 Burnet Ave Cincinnati, Oh 45229 Timing: Fiscal Year 2003; Project Start 07-JUL-2003; Project End 30-JUN-2007 Summary: (provided by applicant): The long-term goals of this work are to study the functional roles of nuclear receptor co-activators in mediating signaling pathways critical to lung development and surfactant protein B (SP-B) gene expression in respiratory epithelial cells. Co-activators including p160 family members (SRC-1, ACTR and TIF2) and CBP/p300 possess histone acetyltransferase (HAT) activity and are known to play important roles in gene activation, cell differentiation and proliferation. The state of the art approaches of biochemical/molecular biology and conditional transgenic mouse models will be utilized. The specific aims are: 1): Characterization of SP-B chromatin acetylation in H441 cells to test hypothesis that histones in the SP-B promoter/enhancer region are hyperacetylated during transcriptional activation. Chromatin cross-linking and chromatin immunoprecipitation (CHIP) assays will be performed; 2): Characterization of trans-interactions between nuclear receptor coactivators and TTF-1 to test hypothesis that nuclear receptor co-activators interact directly with TTF-1 to control target SP-B gene expression. Co-immunoprecipitation, Western blot, GST pulldown and mammalian two-hybrid system will be performed to identify the precise interacting domains of both nuclear receptor co-activators and TTF1; 3): Characterization of TTF-1 acetylation by nuclear receptor co-activators to test hypothesis that nuclear receptor co-activators acetylate TTF-1 in lung epithelial cells. Specific nuclear receptor co-activators (e.g. SRC-1, ACTR, CBP/p300) acetylating TTF-1 will be identified. The precise acetylated lysine residues on TTF-1 will be identified by domain mapping and site-specific mutagenesis; 4): Characterization of dominant
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negative RAR in doxycycline-regulatable transgenic mice to test hypothesis that nuclear receptor co-activators are critical to lung development and recovery/remodeling of respiratory epithelial cells from emphysema. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •
Project Title: ONCOGENIC EVENTS IN THYROID NEOPLASIA Principal Investigator & Institution: Fagin, James A.; Professor; Internal Medicine; University of Cincinnati 2624 Clifton Ave Cincinnati, Oh 45221 Timing: Fiscal Year 2003; Project Start 21-DEC-1996; Project End 31-DEC-2007 Summary: (provided by applicant): Despite their clonal origin cells from advanced carcinomas are often genetically heterogeneous Tumor cell variability is thought to result from genomic instability Clonal heterogeneity in turn predicts a poor outcome, and resistance to therapy. We propose that in thyroid tumors, the nature of the oncogenic events involved in the initiation of the neoplastic clone may determine the likelihood of genomic instability occurring at a later stage. Among the various forms of thyroid neoplasia follicular carcinomas are commonly aneaploid, whereas abnormalities in chromosome number are comparatively less frequent in papillary thyroid carcinomas Mutations of Ras are most prevalent in benign and malignant follicular neoplasms, and believed to be one of the early steps in thyroid tumor formation. In this proposal we will test the hypothesis that tumor initiation by constitutively activated Ras predisposes thyroid cells to chromosomal instability, and will explore the effector systanu involved Acute expression of oncogenic Ras in thyroid cells pre-synchronized at the G1/S boundary accelerates passage through G2/M, and causes defective DNA damage and mitotic spindle assembly checkpoints. This is followed by chromosome misalignment, multiple spindle formation, centrosome amplification and generation of micronuclei. Although constitutive activation of MAP kinase is a mediator of chromosomal instability in this model, the possible role of other effector pathways of Ras is unknown The following aims are proposed: 1) The relative contribution of the Raf-MEK-ERK compared to alternative effectors on cell cycle progression through G2/M, checkpoint function and chromosomal instability will be determined by doxycycline-induced expression of H-Ras effector domain mutants that either signal selectively through Raf (V12S35), or are unable to do so (V12C40; V12S37). The Raf dependency of the effects will be further tested after acute expression of a constitutively activated Raf1 (Raf-BXB), or of a mutant of Raf-BXB that does not activate MEKs 2). We will determine whether inappropriate MEK activation mediates Ras disruption of the DNA damage response, and define whether MEK2 is preferentially involved. We will also characterize MEK2 interacting proteins with which it associates during (32 arrest 3) The biological significance of oncogenic H-ras effects on genomic stability will be determined in vivo in mice with a thyroid-specific knock-in of H-ras V12 4) We will establish whether anenploidy in thyroid neoplasms is associated with a high prevalence of Ras mutations Although Ras mutations and aneuploidy are more prevalent in follicular neoplasms than in papillary carcinomas, this association has not been rigorously established. This would be consistent with the notion that Ras mutation, in thyroid cells induce a "mutator" phenotype, and are thus more likely to undergo phenotypic progression. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen
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Project Title: OUTPATIENT TREATMENT OF PELVIC INFLAMMATORY DISEASE (PID) Principal Investigator & Institution: Soper, David E.; Medical University of South Carolina 171 Ashley Ave Charleston, Sc 29425
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Doxycycline
Timing: Fiscal Year 2001 Summary: The primary aims of this study are to test the effectiveness and cost- effectiveness of outpatient versus inpatient treatment for pelvic inflammatory disease in preventing involuntary infertility. Randomization will be to either outpatient single dose of parenteral cefoxitin with probenecid, followed by oral doxycycline for 14 days or inpatient parenteral cefoxitin and doxycycline for at least 48 hours, followed by oral doxycycline to complete a 14 day course. This multi-center study is sponsored by the AHCPR under the NIH. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •
Project Title: OXIDATIVE (COLLABORATIVE R01
MECHANISMS
OF
AAA
FORMATION
Principal Investigator & Institution: Heinecke, Jay W.; Professor; Internal Medicine; Washington University Lindell and Skinker Blvd St. Louis, Mo 63130 Timing: Fiscal Year 2001; Project Start 30-SEP-1999; Project End 31-AUG-2002 Summary: Abdominal aortic aneurysms (AAAs) are a common degenerative disease with life-threatening implications. While the pathophysiologic events underlying the development of AAA are still poorly understood, they clearly involve degenerative remodeling of aortic wall connective tissue. Recent studies have implicated three processes in this pathologic pattern of remodeling: (1) impaired repair of fibrillar extracellular matrix proteins, (2) chronic mononuclear inflammation, and (3) excessive local production of matrix-degrading proteinases. The purpose of this collaborative research program is to gain better understanding of the molecular mechanisms regulating these three processes. First, Drs. William C. Parks and J. Michael Shipley will examine the molecular factors that appear to limit the effective production of elastic fibers in the aneurysm wall environment. Using tissues obtained from human and experimental AAA and aneurysm-derived vascular smooth muscle cells in culture, they will specifically evaluate the molecular pathways controlling tropoelastin gene expression and tropoelastin mRNA stability, as well as the regulation of additional gene products involved in elastic fiber assembly, such as fibrillin-1 and latent TGF-beta binding protein-2. Second, Dr. Jay Heinecke will examine protein oxidation associated with chronic inflammation as an important pathway of tissue destruction. Using novel methods to detect and measure the contributions of different oxidative pathways to protein modification, he will determine the dominant oxidative pathways in human and experimental AAA, elucidate how protein oxidation serves to promote matrix metalloproteinase activity in aneurysm tissue, and examine how genetic manipulation affecting specific oxidative pathways might alter aneurysm development in a mouse model. Third, Dr. Robert W. Thompson will examine the regulated expression of three different interstitial collagenases, both in human AAA tissues from various stages of disease and in cultured SMC exposed to proinflammatory cytokines, phorbol ester and doxycycline. These studies will have a particular focus on collagenase-3 (MMP-13), providing new insight into the regulation of MMP-13 expression in vascular wall cells. Knowledge gained through these three closely-linked studies will help advance our understanding of the molecular pathophysiology of aortic aneurysms, potentially leading to new treatment strategies. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen
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Project Title: PACAP OVEREXPRESSION AND VOIDING FUNCTION Principal Investigator & Institution: Schwarz, Edward M.; Associate Professor; Orthopaedics; University of Rochester Orpa - Rc Box 270140 Rochester, Ny 14627 Timing: Fiscal Year 2003; Project Start 30-SEP-2003; Project End 31-AUG-2005 Summary: (provided by applicant): Interstitial Cystitis (IC) is a chronic irritative voiding syndrome that occurs without objective evidence of disease and is characterized by urinary frequency, nocturia, urgency, suprapubic pressure, and bladder or pelvic pain. The etiology(s) is currently unknown, and there are no reliably effective treatments. Many patients are left to suffer for the rest of their lives with this incapacitating condition. We hypothesize that IC develops when a barrier defect induces the expression of neuropeptides that transmit signals in the central nervous system (CNS), establishing the neuropathological hallmarks of the disease. Pituitary adenylate cyclaseactivating polypeptide (PACAP) is a leading candidate neuropeptide in the regulation of bladder function and upregulates in bladder afferent cells in the dorsal root ganglia (DRG) in cystitis models. It has been demonstrated recently that PACAP antagonists delivered intrathecally or intravesically can improve bladder overactivity in rodents with cystitis. Here we propose to develop two transgenic mouse models of PACAP over-expression in a tissue-specific manner to evaluate the role of this factor in the neurotrophic mechanisms and lower urinary tract plasticity associated with cystitis. These mouse models will have broad appeal to address not only PACAP's contribution to micturition reflexes, but also PACAP's role in nociceptive mechanisms in general. In a somatic mosaic model, PACAP38 will be over-expressed selectively in bladder sensory neurons following a direct bladder wall injection of a recombinant retrovirus that expresses the cDNA from the neuronal enolase specific promoter. We will also make mice that harbor a PACAP38 transgene whose transcription is controlled by a tetracycline-inducible promoter. These mice (TREPACAP38) will be crossed with our UPII-rtTA transgenic mice that express the reverse tetracycline transactivator only in urothelial cells. These bitransgenic mice (Uro-TetON-PACAP38) will receive doxycycline in their drinking water to evaluate the effect of drug-inducible PACAP over-expression in the bladder. Initial studies to validate the in vivo expression of PACAP38 and its effects on voiding function will be performed. If successful, the mice will be distributed to interested labs to assist with the rigorous characterization of the models as they relate to the neurochemical organization of voiding function. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen
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Project Title: PATHOGENESIS STUDIES IN SCRAPIE (TSE DISEASES) Principal Investigator & Institution: Oldstone, Michael Ba.; Professor; Scripps Research Institute 10550 N Torrey Pines Rd La Jolla, Ca 920371000 Timing: Fiscal Year 2003; Project Start 30-SEP-2003; Project End 31-MAY-2007 Summary: (provided by applicant): Transmissible spongiform encephalopathy (TSE) or prion diseases are rare fatal neurodegenerative illnesses of humans and other animals. The recent awareness of TSE diseases has accelerated due to the appearance of bovine encephalopathy or mad cow disease in Europe, especially the United Kingdom, and its potential for transmission via the food chain to humans and the awareness that the majority of deer and elk on farms as well as 10 to 20% of wild deer and about 1% of elk develop TSE disease (CWD). The transmission of CWD to humans is unknown and although there is currently no evidence of passage of TSE via blood products in humans exposed to BSE, the reported transmission by blood in ruminants is of concern. Our hypothesis is that uniquely designed and developed transgenic (tg) models offer the
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Doxycycline
opportunity to address important but as yet unknown or unresolved issues in TSE diseases. Towards that end we have successfully developed a tg model using PrP ko mice as a host in which expression of PrPsen can be induced in a rev tet system with administration of doxycycline, and a tg model in which GP1 anchorless PrPsen is also expressed in other PrP ko mice. The former will allow data on the turnover of PrPres in vivo and provide information as to its removal, information of value to determine the potential efficacy of anti-PrP therapy during different timed stages of disease. The later GP1-/- model should provide data on glycosylation, spread or failure to spread PrPres from the inoculated site, the ability of GP1 anchorless PrPsen to be converted to PrPres to cause disease, as well as analysis of potential differences in incubation time/disease incidence among different strains of mouse scrapie. The third tg model is the expression of white tail deer (WTD) prion under control of the mouse PrP promoter in PrP ko mice. This model should be useful to study pathophysiology of CWD as well as probing CWD strain differences. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •
Project Title: PROTEOMICS OF COMPLEX 1 INHIBITION IN GSH-DEPLETED CELLS Principal Investigator & Institution: Gibson, Bradford; Professor; Buck Institute for Age Research Novato, Ca 94945 Timing: Fiscal Year 2003; Project Start 01-APR-2003; Project End 31-MAR-2005 Summary: (provided by applicant): Oxidative stress appears to play an important role in degeneration of dopaminergic neurons of the substantia nigra (SN) associated with Parkinson's disease (PD). The SN of early PD patients have dramatically decreased levels of the thiol tripeptide glutathione (GSH). GSH plays multiple roles in the nervous system both as an antioxidant and a redox modulator. Recently, we generated dopaminergic cell lines in which levels of GSH can be inducibly down-regulated via doxycycline (dox) induction of antisense messages against both the heavy and light subunits of gamma glutamyl cysteine synthetase (gamma-GCS), the rate-limiting enzyme in glutathione synthesis. Down-regulation of GCS results in reduction in mitochondrial GSH levels, increased oxidative stress, and decreased mitochondrial function. Interestingly, decreases in mitochondrial activities in GSH-depleted PC12 cells appears to be due to a selective inhibition of complex I activity similar to that observed in PD. This loss in enzymatic activity appears to be a result of cysteine oxidation which is reversible by the thiol-reducing agent dithiothreitol. These results suggest that early observed GSH losses in PD may be directly responsible for the noted decreases in complex I activity and the subsequent mitochondrial dysfunction which ultimately leads to dopaminergic cell death associated with the disease. The hypothesis we will examine in this proposal is that oxidation of specific cysteines within the protein subunits of mitochondrial complex I are responsible for the selective inhibition of its activity following GSH depletion. To accomplish this goal, we will employ a series of sulfhydryl-specific probes to assess the redox states of cysteine thiol groups in complex I proteins. We will use highly sensitive mass spectrometry-based proteomics methods to identify the cysteine residue(s) that are responsible for this reversible loss of mitochondrial complex I activity. We will also examine complex I proteins for other types of oxidative damage (both reversible and irreversible) that may contribute to this loss of activity. These data should provide valuable insight into the effect of oxidative stress on mitochondrial physiology as it relates to PD, particularly the structural basis for alterations in mitochondrial function. Knowledge of the molecular details of complex I dysfunction and the identification specific subunit(s) that are involved may point us
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towards novel therapeutic targets for the disease and provide key data on whether thiol replacement therapy is a viable option for treatment of the disease. Once identified, presence of these alterations will be assessed in future years in both an antiGSH transgenic mouse model of Parkinson disease as well as in Parkinsonian brains. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •
Project Title: EXPRESSION
REGULATING
AAV-MEDIATED
RETINAL
TRANSGENE
Principal Investigator & Institution: Dejneka, Nadine S.; Ophthalmology; University of Pennsylvania 3451 Walnut Street Philadelphia, Pa 19104 Timing: Fiscal Year 2001; Project Start 01-JUL-2001 Summary: Retinitis pigmentosa (RP) is a group of inherited retinal disorders affecting rod photoreceptors, leading to blindness. Mechanisms responsible for RP are not understood; however, a number of mutations have been identified in retina-specific genes, including rhodopsin, suggesting that these mutations are responsible for the disease. Viral gene transfer techniques have been used to deliver corrective genes to animal models of RP. There is strong evidence that this mode of therapy will have great promise in the eye; however, success of the technique will depend upon tight regulation of transgene expression. Consequently, the long term goals of the proposed research are two4old: 1) to evaluate the efficiency of adeno-associated virus (AAV)-mediated retinal transgene expression using an exogenously regulatable tetracycline-based (TetOn) promoter system; and 2) to use an externally regulatable transgene system incorporated into AAV to attempt to rescue the retinal degeneration occurring in the rhodopsin knockout (RKO) mouse. For the first goal, the regulation of photoreceptor specific transgene expression will be evaluated in C57BI/6 mice, using the TetOn promoter system carrying the reporter gene green fluorescent protein (GFP). For rescue experiments, the appropriate AAVs carrying rhodopsin and the essential components of the TetOn system will be prepared and delivered to photoreceptors of the RKO mouse. Transgene expression will be modulated by administering and removing doxycycline from drinking water at different times, and transgene levels will be monitored by RNA analysis. Photoreceptor rescue will be assessed histologically. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •
Project Title: REGULATION HYPERTENSION
OF
AT1R
ANTISENSE
IN
CONTROL
OF
Principal Investigator & Institution: Francis, Sharon C.; Physiology and Functional Genomics; University of Florida Gainesville, Fl 32611 Timing: Fiscal Year 2002; Project Start 01-JAN-2002 Summary: Hypertension is a major risk factor for cardiovascular disease and has emerged as a tremendous economical and emotional burden on society. Thus, it is imperative that a permanent treatment and cure for this disease is discovered. We have developed a model that uses a retroviral-mediated gene delivery system to deliver antisense to the type 1 angiotensin receptor (AT1R-AS) to 5-day old rats. This delivery has profound beneficial effects on blood pressure and cardiac and renal pathophysiology in both the spontaneous hypertensive rat genetic model and in the chronic angiotensin II acquired hypertension model. Unfortunately, this system does not address critical issues of safety and efficacy. The ability to regulate expression of the therapeutic gene is crucial, because the therapeutic window or level of AS gene that is needed may vary during the course of the disease or between hypertensive individuals.
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Doxycycline
Additionally, in cases of unanticipated side- effects it will be important to switch off expression of the AS gene. The purpose of this proposal then, is to develop a regulatable system for AT1R-AS wherein issues of safety and efficacy can be tested. We propose to infect two animal models of hypertension (genetic and acquired) with retroviral vectors harboring AT1R-AS under a tetracycline-regulatable promoter We will use these models to test the hypothesis that doxycycline, (Dox) a potent tetracycline derivative, can induce AT1R-AS expression and thus regulate its subsequent antihypertensive effects. Thus, specific aims of this research program will be as follows: 1. To characterize the efficiency and efficacy of RevTRE-AT1R-AS In vitro, 2. To determine the expression potential, physiological and cellular consequences of Dox-controlled AT1R-AS expression. 3. To test the efficacy of the Dox AT1R-AS system in chronic Ang II infusion model of hypertension.This project will have a profound impact on the way to treat and control hypertension and other cardiovascular diseases. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •
Project Title: REGULATION OF B CELL DEVELOPMENT BY RAS AND RAF Principal Investigator & Institution: Farrar, Michael A.; Assistant Professor; Lab Medicine and Pathology; University of Minnesota Twin Cities 200 Oak Street Se Minneapolis, Mn 554552070 Timing: Fiscal Year 2002; Project Start 01-MAY-2002; Project End 30-APR-2003 Summary: (provided by applicant): B cells play an essential role in the establishment of a functional immune response against bacteria and viruses. Therefore, the process of B cell development must produce a population of mature B cells with both sufficient diversity of antigen receptors and sufficient numbers of cells. In order to mount an effective defense against the vast array of potential infectious agents, signals entrained by the Ras/Raf pathway regulate early B cell differentiation at the earliest pre-pro-B stage, in essence determining the number of cells that proceed down this developmental pathway. However, the upstream activators and downstream effectors of this pathway remain undefined. Our hypothesis is that the Ras/Raf pathway is activated by the interleukln-7 or flk2/flt3 receptors, and that it affects downstream responses by altering the expression of transcriptional regulators, specifically members of the Id- and Eta-gene families. Thus the aims of this application are: (1) To determine whether the IL7R or flk2/flt3 entrain early B cell development via Ras activation, (2) To determine whether Ras/Raf-dependent early B cell differentiation involves regulation of Id- or Ets-family proteins, and (3) To identify Ras/Raf-dependent transcription factors involved in regulating pre-pro-B cell differentiation. A number of strategies will be utilized to achieve these goals. First, biochemical approaches will be used to determine whether either lL7 or flt3L can activate the Ras/Raf pathway in pro-B cell lines or in ex vivo prepro-B cells. Second, genetic approaches that involve transgenic mice which express constitutively active forms of Raf (Raf-CAAX) will be used to determine whether forced Ref activation can rescue B cell development In IL7R- or flk2/flt3-deflcient mice. Third, transgenic mice which express either dominant negative Ras or constitutively active Rat in developing B cells will be utilized to determine whether this pathway regulates expression of Id-or Ets-family members. These experiments will be extended using inducible approaches for activating the Ref pathway in vivo. Specifically, these include (I) chemical induced dimerization of Raf-GyrB fusion proteins utilizing the symmetrically dimeric small molecule coumermycin, and (ii) doxycycline-regulated transcription of activated forms of Raf (Raf-CAAX). Finally, gene microarray technology will be applied, in conjunction with the mouse mutants described above, to identify novel targets of the Ras/Raf pathway involved in pre-pro-B cell differentiation. These
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studies should help to illuminate the molecular mechanisms by which the Ras pathway regulates B cell differentiation. The importance of clarifying this process has been highlighted recently by the observation that B cell reconstitution following bone marrow transplantation frequently proceeds poorly, resulting in patient susceptibility to a number of bacterial pathogens. Thus a better understanding of early B cell development should prove useful for optimizing bone marrow transplantation protocols in the future. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •
Project Title: REGULATION OF TRANSTHYRETIN IN THE LIVER Principal Investigator & Institution: Costa, Robert H.; Professor; Molecular Genetics; University of Illinois at Chicago 1737 West Polk Street Chicago, Il 60612 Timing: Fiscal Year 2003; Project Start 01-JUL-1990; Project End 30-JUN-2007 Summary: (provided by applicant): Cellular differentiation is associated with transcriptional induction of distinct sets of cell-type-specific genes whose expression is required for organ function. Deciphering the mechanisms that control cell-type-selective transcription is critical to understanding cellular differentiation. Studies of liver-specific DNA regulatory regions suggest that selectivity of hepatocyte-specific gene transcription relies on multiple DNA sequences that recruit binding and combinatorial interactions of distinct families of hepatocyte nuclear factors (HNF) to provide synergistic transcriptional activation. However, the mechanisms by which these liver transcription factors mediate synergistic transcriptional activation have not yet been clarified. We demonstrated that interactions between the Forkhead Box (Fox) A2 (HNF3beta) and HNF-6 DNA binding domains result in stimulation of FoxA2 transcriptional activity through the recruitment of the p300/CBP coactivator proteins, while this protein complex antagonizes the ability of HNF-6 to recognize its target DNA sequence. Furthermore, we demonstrate that CCAAT/Enhancer Binding protein a(C/EBPalpha), but not the related C/EBPbeta protein, interacts with and provides transcriptional synergy with HNF-6 and that this protein complex leads to inhibition of C/EBPa target genes. The fact that the insulin-phosphatidylinositoi 3'-kinase (PI3K)-Akt signal transduction pathway inhibits HNF-6 transcriptional activation thus identifies a signaling pathway for regulating activity of these transcriptional synergies. Our studies suggest the hypothesis that interactions between liver transcription factors result in both transcriptional synergy and inhibition, thus providing a mechanism, which achieves diverse transcriptional function in response to transcription factor protein levels or activity. We will further characterize mechanisms of synergy and inhibition between hepatic transcription factors and investigate their regulation by the insulin-Akt pathway in vivo with the following four specific aims: 1) We will test the hypothesis that diminished HNF-6 transcriptional activity is due to Akt phosphorylation directly or indirectly through Akt inhibition of Glycogen Synthase Kinase 3 (GSK-3) activity. We will determine whether the Akt pathway negatively regulates HNF6-FoxA2 transcriptional synergy. 2) We will examine whether inhibiting HNF6-FoxA2 transcriptional synergy in vivo with a doxycycline inducible HNF6 dominant negative protein disrupts liver development and adult hepatocyte gene expression. 3) We will define the sequences involved in mediating liver-specific C/EBPa-HNF6 transcriptional synergy. We test the hypothesis that both the Akt pathway and increased C/EBPbeta levels negatively regulate C/EBPalpha-HNF6 transcriptional synergy. 4) We will use the Chromatin Immunoprecipitation (CHIP) assay to examine whether the HNF-6, FoxA2 and C/EBPalpha proteins form synergistic complexes with liver target promoters in vivo. Completion of these studies will provide a better understanding of the
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mechanisms involved in transcriptional synergy and inhibition among liver transcription factors, which mediate regulation of hepatocyte-specific gene expression. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •
Project Title: ROLE OF GLUTATHIONE REDUCTASE AND MACROPHAGE ONCOSIS Principal Investigator & Institution: Asmis, Reto Hr.; Medicine; University of Kentucky 109 Kinkead Hall Lexington, Ky 40506 Timing: Fiscal Year 2002; Project Start 01-AUG-2002; Project End 31-JUL-2006 Summary: (provided by applicant): We hypothesize that increased glutathione reductase activity protects human macrophages from OxLDL-induced mitochondrial dysfunction and cell death, thereby decreasing the severity of atherosclerosis. Macrophage and foam cell death by oncosis plays a crucial role in the development of atherosclerotic lesions. We propose to study the molecular mechanism of glutathione reductase-mediated protection of macrophages from oncosis.Specific Aim 1: To determine the effect of OxLDL on the thiol redox state of mitochondria. Our preliminary data demonstrate that OxLDL induces mitochondrial depolarization and loss of ATP synthesis. We will use human monocyte-derived macrophages to determine if OxLDL promotes oncosis by 1) altering the thiol redox status of mitochondria, 2) inactivating mitochondrial glutathione reductase and 3) increasing mitochondrial inner membrane permeability.Specific Aim 2: To determine the role of mitochondrial and cytosolic glutathione reductase in preventing OxLDL-induced oncosis. Mitochondria do not synthesize glutathione (GSH) and therefore rely on GSH uptake and the reduction of GSSG to maintain the appropriate thiol redox state. We will use human monocytederived macrophages to determine 1) if adenovirus-mediated doxycycline-controlled expression of mitochondrial or cytosolic glutathione reductase (GR) prevents GSSG accumulation and protein thiol oxidation and 2) if increasing glutathione reductase activity restores mitochondrial function and protects macrophages from OxLDLinduced oncosis.Specific Aim 3: To determine whether increased macrophage glutathione reductase activity decreases the severity of atherosclerosis. Foam cell death promotes the formation of the necrotic core and the progression of atherosclerotic lesions. We will perform bone marrow transplantation studies to determine in vivo whether augmented expression of glutathione reductase (GR) in macrophages prevents foam cell death and lesion progression. GR-overexpressing bone marrow cells, generated by retroviral gene transfer, will be used to repopulate irradiated LDL receptor null mice and apoE null mice. We will measure both lesion size and lesional cholesterol/cholesterol ester content. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen
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Project Title: ROLE OF MACROPHAGE SPECIFIC GENE EXPRESSION IN ATHEROGENESIS Principal Investigator & Institution: Glass, Christopher K.; University of California San Diego 9500 Gilman Dr, Dept. 0934 La Jolla, Ca 92093 Timing: Fiscal Year 2001 Summary: Monocyte-derived macrophages play a central role in the pathogenesis of atherosclerosis. They actively promote oxidation of LDL, express scavenger receptors, and secrete cytokines and growth factors which influence the migration, growth and function of arterial cells. They may also contribute to plaque instability b secretion of metalloproteinases. Our laboratory characterized transcriptional control elements of the
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scavenger receptor A (SR-A) gene that are required for macrophage-specific expression of this gene. We also demonstrated that regulatory elements of the SR-A gene can be used to specifically target reporter reporter gene expression in macrophage foam cells of murine atherosclerotic lesions. A major aim of this unit is to fully develop and validate a variety of vector systems for the overexpression or disruption of genes in a macrophagespecific manor. Vector based on the SR-A promoter and other macrophage-specific promoters will be developed to allow targeting of cDNAs to mature macrophages and macrophage progenitor cells. These vectors will also be used to direct expression of Crerecombinase or a doxycycline-inducible transcriptional activator in transgenic mice. The ability of these vectors to direct efficient macrophage-specific expression of genes in forms cells of atherosclerotic lesions will be assessed in apo E- deficient, or LDL receptor-deficient (LDLR) mice, utilizing reporter genes, such as human growth hormone. A second aim will be to utilize this information to determine the impact on atherogenesis of macrophage specific overexperssion of genes that could influence atherogenesis. Overexpression of 15-lipoxygenase will serve as an example of a gene that can enhance the oxidation of LDL, and overexpression of phospholipidhydroperoxide glutathione peroxidase as an example of a gene that should decrease oxidation of LDL. In a similar manner we will determine the consequences to the integrity of the artery wall of macrophage-specific overexpression of metalloproteinases, including the 92 kDa gelatisase, interstitial collagenase, and stromelysin, expressed individually and in combination. The effects of overexpression of these genes on the atherosclerotic process will be tested in appropriate murine models. Finally, we will determine the consequences for atherogenesis of macrophage-specific disruption of the c-jun gene. C-jun appears to regulate transcription of several important macrophase genes, including SR-A, cytokines, and metalloproteinases. Because a global disruption of c-jun results in embryonic lethality, macrophage-specific disruption will serve as a paradigm for the evaluation of gene required for normal development but which may contribute to atherogenesis. The information gained from these studies should yield fundamental insights into the role that macrophages play in atherogenesis and could be used to develop novel and effective therapeutic strategies. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •
Project Title: ROLE OF NFI IN TYPE II CELL FUNCTION Principal Investigator & Institution: Bachurski, Cindy J.; Assistant Professor; Children's Hospital Med Ctr (Cincinnati) 3333 Burnet Ave Cincinnati, Oh 45229 Timing: Fiscal Year 2003; Project Start 01-JUL-1998; Project End 30-JUN-2007 Summary: (provided by applicant): Branching morphogenesis of the lung is controlled by well-orchestrated signaling cascades between the developing epithelial and mesenchymal compartments. However, the complex transcription factor interactions that regulate lung epithelial differentiation remain poorly understood. Thyroid transcription factor 1 (TTF1) and GATA6 have been implicated in differentiation of the distal pulmonary epithelium and we have clearly shown that Nuclear Factor I (NFI) regulates surfactant protein-C gene expression. We also identified NFI binding sites in the promoters of several other lung epithelial specific genes. Our preliminary data suggests that NFI interacts with both TTF1 and GATA6 and is critical for proper lung development and Type II cell maturation. All NFI family members are expressed in adult Type II cells, however genetic inactivation of Nfib, but not Nfia, causes neonatal death by respiratory failure due to a block in lung maturation. This proposal will test the hypothesis that NFIB coordinates the interaction of other transcription factors and cofactors to regulate distal lung morphogenesis, proliferation, and Type II cell specific
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gene expression. We hypothesize that NFI plays a major role in inhibiting cell proliferation during cytodifferentiation and in the adult lung. The goals of this proposal are to 1) determine the role of NFI in pulmonary epithelial cell proliferation and differentiation in vivo and in vitro using doxycycline regulated overexpression and "dominant-repressor" strategies; 2) determine whether epithelial expression of a single isoform of Nfib in Nfib gene targeted mice is sufficient to induce progression of lung development and distal epithelial cytodifferentiation; 3) identify the protein-protein interactions that modulate NFI transcriptional activity in Type II cells. The current proposal will define novel molecular mechanisms by which NFI regulates epithelial cytodifferentiation and morphogenesis of the developing lung. These studies may provide a basis for the rational design of new treatment strategies for neonatal pulmonary disease and bronchopulmonary dysplasia. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •
Project Title: ROLE OF SPARC IN GLIOMA INVASION Principal Investigator & Institution: Rempel, Sandra A.; Director; Neurological Surgery; Case Western Reserve Univ-Henry Ford Hsc Research Administraion Cfp-046 Detroit, Mi 48202 Timing: Fiscal Year 2001; Project Start 16-APR-2001; Project End 31-MAR-2004 Summary: (Adapted from the investigator's abstract) The poor prognosis of glioma patients is largely due to the highly invasive nature of these tumors. We have demonstrated that SPARC is highly expressed in gliomas and that it functionally contributes to invasion in vitro. Importantly, our Preliminary Data show that SPARC promotes invasion in vivo. The focus of this proposal is to determine the mechanisms by which SPARC expression promotes brain tumor invasion. In Specific Aim 1. we will determine the extent to which SPARC functionally promotes glioma invasion by: la) Characterizing the effects of SPARC expression on tumor cell invasion during the course of tumor development in viva. We will use doxycycline (dox)-regulatable SPARCtransfected U87 glioma clones in a nude rat xenograft model to evaluate the effects of increased SPARC expression on the extent of tumor cell invasion, angiogenesis. necrosis, proliferation, and overall tumor growth during the course of tumor progression. ib) Determining whether tumor-expressed SPARC is sufficient for tumor invasion in vitro. We will assess tumor invasion into normal and Sparc knockout fetal aggregates in the in vitro spheroid confrontation assay. ic) Determining the extent to which loss ol SPARC expression inhibits brain tumor invasion in viva. We will use a SPARC-targeting construct and homologous recombination to create a SPARC knockout in the C6 glioma cell line that will be assessed as in Specific Aim 1a. In Specific Aim 2, we will determine the biological mechanism(s) by which SPARC promotes tumor invasion. We will use our U87T2 parental clone and SPARC-transfected clones (+/- dox), serum-free C6 (+/SPARC), and Sparc (-/-) and (+7+/-) fetal astrocytes to: 2a) Analyze how SPARC promotes the critical intermediate stage of adhesion. We will use the three cell models in timed studies using different concentrations of brain ECM molecules. We will assess the effect of SPARC on 1) attachment, 2) spreading, 3) or formation of focal adhesions and stress fibers via its affects on integrins and focal adhesion-associated proteins. 2b) Determine whether SPARC promotes migration in a concentration-dependent, ECMspecific manner. We will use the three cell models to perform migration assays using different concentrations of ECMs. Migration will be assessed using the cell sedimentation assay, the wounding assay, and Boyden chambers. 2c) Determine whether SPARC promotes invasion by reducing the proliferation rate of tumors. We will assess SPARC's effect on proliferation by performing 1) growth curves for the three cell
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models on specific brain ECM molecules, as well as perform 2) anchorage-independent growth assays, and 3) FACS analyses under the same conditions. Direct effects of SPARC on cell cycle progression will be monitored for changes in cyclin A, tk, and p107 expression and/or phosphorylation. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •
Project Title: SCOR IN PATHOBIOLOGY OF LUNG DEVELOPMENT Principal Investigator & Institution: Whitsett, Jeffrey A.; Professor and Director of Pediatrics; Children's Hospital Med Ctr (Cincinnati) 3333 Burnet Ave Cincinnati, Oh 45229 Timing: Fiscal Year 2001; Project Start 01-SEP-1996; Project End 31-JUL-2006 Summary: (Applicant's Abstract) The present application focuses its primary attention to discerning the principles of lung morphogenesis and repair in vivo and is based on the ability to precisely target, mutate or add genes to respiratory epithelial cells and mesenchymal cells of the developing mouse embryo. Major breakthroughs have been made by the SCOR investigators in developing conditional systems for gene regulation in vivo, now enabling gene targeting, via doxycycline controlled cre-recombinase in the developing and mature lung. These new technologies will be applied to important pathways mediating 1) lung formation (TTF-1, HNF-3beta and FGF-signaling pathways; 2) lung function, remodeling and inflammation (SP-C and SP-D). Clinical translation of information gained from these molecular models will extend our understanding of the cellular signals and molecular events regulating development and the pathogenesis of acquired lung disease in neonates and adults. Each project will require the generation and analysis of transgenic mice in which the animal is modified by adding correct or mutated genes which are expected to alter lung development or lung function in unique ways. The analysis data from each of the planned projects requires shared scientific expertise, approaches and reagents, and use similar biochemical, immunochemical, histologic, metabolic and physiological endpoints. The comprehensive analysis of each of the various gene knockouts and gene addition experiments are best accomplished in context of highly organized Core settings where developing technology, reagents and ideas can be rapidly shared among the various investigators. Cores for Molecular Morphology, Transgenic Animals, and Clinical Studies will greatly facilitate the scientific progress of the individual projects. Project 1. Respiratory Epithelial Cell Differentiation (TTF-1, HNF-3beta), J. A. Whitsett, P.I. Project 6. Fibroblast Growth Factors in Lung Morphogenesis, J. Shannon, P.I. Project 2. Role of SP-D in Pulmonary Remodeling, T. Korfhagen, P.I. Project 7. SP-C Mutations and Neonatal Lung Disease, T. E. Weaver, P.I. Core 9004. Transgenic Core, J.A. Whitsett, P.I. Core 9002. Morphology Core, S. Wert, J. Shannon, P.I. Core 9005. Clinical Core, S. Wert, P.I. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen
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Project Title: ANTHRACIS
TARGET
AND
ANTIBIOTIC
DISCOVERY
Principal Investigator & Institution: Youngman, Philip Pharmaceuticals, Inc. 3510 Dunhill St San Diego, Ca 921211212
J.;
IN
BACILLUS
Professor;
Elitra
Timing: Fiscal Year 2002; Project Start 15-JUL-2002; Project End 14-FEB-2004 Summary: (provided by applicant): By simply growing Bacillus anthracis in the presence of sub-inhibitory concentrations of antibiotics it has been made resistant to all commonly used drugs such as penicillin, doxycycline and Ciprofloxacin. If one of these antibiotic resistant strains were used in a future terrorist attack there will be limited or
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no therapeutic treatments available. Thus there is an urgent need to develop new classes of antibiotics to treat resistant B. anthracis. A shotgun antisense technology is proposed for the rapid identification of B. anthracis essential genes, whose protein products can serve as targets for new classes of antibiotics. This technology conditionally and incrementally reduces the level of an essential gene product, which provides a means to hypersensitize cells to compounds that inhibit that target and thus provides a cell-based assay for drug discovery. Phase I of this proposal will be to develop the molecular biology tools for conditionally delivering random genomic antisense RNA fragments to B. anthracis cells. In Phase II a genome-wide screen in B. anthracis will identify a comprehensive list of essential genes. We have developed a unique microbial relational database, which allows the prioritization of targets based on conservation among bacterial pathogens having no or limited homology to human proteins. Bioinformatics analyses undertaken prior to drug screening should help ensure that new antimicrobial drugs have maximal impact upon the disease and minimal impact on the patient. Cellbased assays will be optimized for these prioritized targets and entered into an established high throughput chemical screening program against the company's chemical library of over 250,000 compounds. This Gene-to-Screen technology platform has been developed to allow miniaturized drug screens to be developed for any validated target within 2-3 weeks. Promising hit compounds would then be rapidly developed and advanced into lead-optimization chemistry. New classes of antibiotics would help deter and treat against future bioterrorist attacks and could also be used to treat common drug resistant pathogens. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •
Project Title: TARGETED MOUSE MODELS OF ALZHEIMER DISEASE Principal Investigator & Institution: Fukuchi, Ken-Ichiro; Genomics and Pathobiology; University of Alabama at Birmingham Uab Station Birmingham, Al 35294 Timing: Fiscal Year 2001; Project Start 01-APR-2001; Project End 31-MAR-2002 Summary: Alzheimer Disease (AD) is a neurodegenerative disorder characterized by the progressive loss of memory and cognitive functions. Cardinal pathological changes found in the brain of patients with AD are neurofibrillary tangles and deposits of aggregated amyloid protein (Abeta) in neuritic plaques and cerebral vessels (cerebrovascular amyloid angiopathy). The pathogenetic mechanisms that lead to development of AD are not clearly understood. There is no satisfactory treatment for AD. Approximately 10% of AD cases are classified as early onset familial AD (FAD) and show autosomal dominant inheritance. Inherited mutations in the gene coding for presenilin 1 (PS1) cause 18 to 50% of the early onset FAD cases. Although PS1 may be a transmembrane aspartyl protease that generates Abeta by cleaving its precursor proteins, neither the physiological functions nor normal metabolism of PS1 are fully understood. Such understanding is essential to establishing the logical basis for therapy and prevention of the disease. Attempts to clarify the physiological functions of PS1 by constructing PS1 deficient (knockout) mice resulted in embryonic lethality. Thus, it is impossible to study the physiological functions and pathogenetic roles of PS1 in the adult using the "conventional" knockout mice. The primary goal of this pilot project is to establish new lines of PS1 knockout mice where expression of the PS1 gene is tightly regulated by the tetracycline (Tc) controllable transactivator system. The Specific Aims of the current research project are to: (Aim 1) isolate targeted embryonic stem (ES) cell lines with a PS1 gene under control of the Tc transactivator system and (Aim 2) establish mutant mouse lines for the PS1 gene using the targeted ES cell lines established in Aim 1 and test the tight regulation of the targeted PS1 genes in the mice. In these new lines of
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mice, expression of the PS1 gene will be turned on during embryogenesis and completely turned off by administration of doxycycline (a derivative of Tc) when the mice become adult. The long-term goal of this research is to elucidate the role of PS1 in the pathogenesis of AD via a thorough understanding of the physiological functions and normal metabolism of PS1. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •
Project Title: TAT INTERACTION WITH LRP AND ITS ROLE IN AIDS DEMENTIA Principal Investigator & Institution: He, Johnny J.; Microbiology and Immunology; Indiana Univ-Purdue Univ at Indianapolis 620 Union Drive, Room 618 Indianapolis, in 462025167 Timing: Fiscal Year 2002; Project Start 19-JUL-2002; Project End 30-JUN-2007 Summary: (provided by applicant): HIV-1 infection of the central nervous system occurs in a majority of AIDS patients, and causes a variety of neurologic dysfunction and neuropathologies. Microglia/macrophages are the major target cells for I-IIV-I infection. It has generally been accepted that neurons that are mostly affected in the brain of HIVpositive individuals are rarely infected by HIV-1. Therefore, a number of indirect mechanisms have been proposed for AIDS-associated neuropathogenesis. Among these is the soluble viral protein Tat. We have recently shown that HIV-1 Tat protein interacts with low-density protein receptor-related protein (LRP) and results in neuronal uptake of Tat protein. Moreover, Tat interaction with LRP leads to extracellular accumulation of LRP physiological but neurotoxic ligands, suggesting that AIDS-associated neuropathology and other neurodegenerative diseases such as Alzheimer's disease, may share a common pathway that eventually leads to dementia. Our preliminary studies demonstrated that Tat expression in the brain of doxycycline (Dox)-regulated, braintargeted Tat transgenic mice results in neuropathologies, reminiscent of those noted in the brain of AIDS patients. The underlying hypothesis for this proposal is that Tat interaction with LRP contributes to AIDS-associated neuropathological disorders including dementia. We propose that HIV-1 Tat protein is a major neuropathogenic factor contributing to HIV-associated neuropathology. To test this hypothesis, we propose the following interrelated specific aims: 1) To determine gene expression by LRP-uptaken Tat; 2) To determine LRP-mediated intracellular signaling elicited by Tat binding; and 3) To determine mechanisms of Tat-induced neuropathology. Experimental approaches include use of the primary mouse cortical neuron cultures, Tat-expressing stable cell lines, and the Dox-regulated, brain-targeted Tat transgenic mouse model. This combined molecular, cellular, biochemical, and genetic approach will provide a better and unique understanding of the highly important and pervasive HIV-1 Tat protein, and its role in HIV-l-induced neuronal injury and neurologic symptoms of AIDS patients. In addition, these studies will also yield new clues for developing anti-HIV therapeutic strategies for treating HIV-associated neurological disorders occurring in the majority of AIDS patients. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen
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Project Title: TET REGULATED VECTORS FOR PARKINSON'S DISEASE Principal Investigator & Institution: Bohn, Martha C.; Director of the Neurobiology Program; University of Rochester Orpa - Rc Box 270140 Rochester, Ny 14627 Timing: Fiscal Year 2002; Project Start 30-SEP-2002; Project End 31-AUG-2007 Summary: The long-term goal of this project is to develop viral vectors that can be used as gene therapy vehicles to treat Parkinson's disease (PD), as well as other chronic
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neurodegenerative diseases. Such vectors require the incorporation of a promoter element that permits effective and safe regulation of the therapeutic gene through peripheral drug administration. The proposed experiments will focus on tetracycline(tet)-regulated promoter systems in the context of recombinant adenoassociated viral vectors (AAV) and tentiviral vectors which are based on the human immunodeficiency virus (HIV). A set of AAV and HIV viral vectors will be made that incorporate cellular marker and therapeutic genes driven by tet-regulated promoters that can be turned-on or turned-off by administration of the tet analog doxycycline (Dox). Cellular marker genes including humanized green fluorescent protein (hrGFP) and an non-immunogenic gene, rat alkaline phosphatase (rAP), will be used to assess the efficiency and suitability of the vector designs. Quantitative assays including flow cytometry, real-time, quantitative reverse transcriptase-polymerase chain reaction (QRTPCR), ELISA and computerized morphometry will be applied to assess and compare vectors in cell culture and in the rat nigrostriatal system. In vivo studies will be clone in both normal intact rat brain and in the 6-OHDA progressively lesioned rat model of PD to determine whether damage related to PD will affect the efficiency of vectors containing regulated promoters. These studies will also determine to what extent the therapeutic effects of glial cell line-derived neurotrophic factor (GDNF) gene therapy in this rat model of PD are reversible. Effects of GDNF gene delivery using tet-regulated vectors on dopamine neurons will be evaluated using quantitative morphometric, molecular and behavioral evaluations. All studies will involve assessment of host immune reactions and chromosomal effects of the vectors in collaboration with the Lowenstein and Federoff labs in this consortium. The successful generation of a viral vector that fulfills the requirements of tight regulation, long-term expression and regulatability with minimal host immune responses in the rat CNS will be advanced to non-human primate preclinical trials for PD. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •
Project Title: THE FUTURE IS NOW:STEM CELLS AND ALCOHOL Principal Investigator & Institution: Zawada, W M.; Assistant Professor; Medicine; University of Colorado Hlth Sciences Ctr P.O. Box 6508, Grants and Contracts Aurora, Co 800450508 Timing: Fiscal Year 2001; Project Start 27-SEP-2001; Project End 31-AUG-2006 Summary: (provided by applicant): Brain dopamine is postulated to modulate alcohol consumption. We hypothesize that reduction in extracellular dopamine (DA) levels would reduce ethanol intake. The main goal of this proposal is to examine if transplantation of neural stem cells (NSCs) modified to overexpress the human DA transporter (hDAT) into specific brain sites can reduce extracellular DA levels and alter ethanol?s behavioral actions. NSCs are pluripotent cells that exist in the developing and adult brain. NSCs have a capacity to differentiate into all known neural type cells including neurons, astrocytes and oligodendrocytes. Unprecedented plasticity of NSCs makes them ideal candidates for genetic modification and transplantation into the central nervous system (CNS). This proposal will explore a novel strategy using stem cell transplantation for moderating alcohol effects and intake. The specific aims of this proposal are: (1) Generation of neural stem cell lines expressing human DAT (hDAT) under control of an inducible promoter. Because cell lines expressing high levels of hDAT suitable for neural transplantation do not exist, we propose to generate a hDATexpressing high neural stem cell line (C17.hDAT) for cell transplantation. We will use mouse v-myc immortalized neural stem cells (C17.2) obtained from Dr. Evan Snyder as the cell line development platform. (2) Examine the hDAT expression and function in
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C17.hDAT stem cell-derived neurons and glia. We propose to examine hDAT expression and function in stem cells differentiated into neurons or glia. This aim will also examine the effectiveness of regulating Tet-On system-driven hDAT expression and function with doxycycline. (3) Determine if transplantation of C17.hDAT stem cells into mouse brain can reduce extracellular dopamine in vivo and alter ethanol?s actions. We will first transplant C17.hDAT cells developed in the aim 1 into the brains of wildtype (wt) and DAT knockout mice provided by Dr. Marc Caron and into the brains of wt mice with high (C57BL/6) and low (DBA) alcohol preference. Target areas for grafting will include nucleus accumbens, prefrontal cortex, amygdala and dorsal striatum. Grafting into DAT knockout mice should reverse the behavioral and biochemical consequences of reduction in DAT levels. Survival of grafted cells and function of transgenic hDAT will be examined. Behavioral testing will examine ethanol-induced locomotor activity and the mice will be exported to other sites in the consortium to test for alcohol preference. These studies will generate hDAT-expressing stem cells for transplantation in the CNS and examine whether stem cell therapy can reduce alcohol?s actions. Such findings will provide the first evidence for use of stem cells in the treatment of drug dependence. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •
Project Title: THE PATHOBIOLOGY OF INHERITED RETINAL DEGENERATION Principal Investigator & Institution: Bok, Dean; Professor; Neurobiology; University of California Los Angeles 10920 Wilshire Blvd., Suite 1200 Los Angeles, Ca 90024 Timing: Fiscal Year 2002; Project Start 01-DEC-1976; Project End 30-NOV-2006 Summary: The proposed research explores mechanisms that underly the pathobiology of inherited retinal disease. A variety of animal models for retinitis pigmentosa will be utilized. Employing the spontaneously- mutated mouse model, retinal degeneration slow (rds) as the genetic background for this work, we will study transgenic lines carrying the rds point mutation P216L on the (rds+/-) background. We used these animals in a preclinical trial for recombinant adeno-associate virus (rAAV)-vectored therapy with ciliary neurotrophic factor (CNTF), a cytokine that has well-documented photoreceptor rescue properties. This treatment produced morphological photoreceptor rescue but it changed the photoreceptor nuclear phenotype and reduced the a and bwave amplitude of the eletroretinogram. We will conduct additional dose response studies to determine whether this side effect can be eliminated and also try to determine the mechanism of the observed effect. These animals will also be used for rAAV-vector, ribozyme-mediated gene therapy. We will use doxycycline-inducible transgenic mice in which a wild type rds rescue transgene can be activated on the rds-/- or rds+/background at various stages during the evolution of retinal degeneration. This will allow us to determine the optimal time for genetic intervention in the disease processes. We will also use a doxycycline-inducible transgenic mouse model in which the P216L point mutation can be switched on at any doxycycline-inducible transgenic mouse model in which the P216L point mutation can be switched on at any point after birth. Additionally, we will utilize a transgenic mouse line that features an X chromosomelinked non-autonomous form of photoreceptor cell death. In these animals, rds-/photoreceptors that express a wild type rds rescue transgene located on their X chromosome degenerate in the presence of neighboring cells that lack expression of the rescue transgene due to X chromosome inactivation. Our approach in the analysis of these animals will involve the use of DNA microarrays in an attempt to identify genes that respond to the presence of the point mutation in a deleterious way and to identify genes involved in the non-autonomous cell death observed in the X-linked transgenic model.
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Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •
Project Title: THE ROLE OF GELATINASE A IN INTERSTITIAL FIBROSIS Principal Investigator & Institution: Cheng, Sunfa; Northern California Institute Res & Educ San Francisco, Ca 941211545 Timing: Fiscal Year 2001; 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 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
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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
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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 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 AND KNOCKOUT MODELS OF ADPKD Principal Investigator & Institution: Harris, Peter C.; Professor of Medicine; Mayo Clinic Rochester 200 1St St Sw Rochester, Mn 55905 Timing: Fiscal Year 2002; Project Start 15-APR-2002; Project End 31-MAR-2007 Summary: We have previously developed transgenic lines that express the human autosomal dominant polycystic kidney disease gene, PKD1, from a large genomic fragment (TPK). The transgene rescues the lethal phenotype of Pkd1-/- mice, but the TPK animals often develop renal and hepatic cystic disease. These results indicated that the level of PKD1 protein, polycystin-1, may be important for maintaining normal renal architecture. The first part of this proposal is to clarify these findings by generating PKD1 transgenic lines with a smaller genomic insert containing PKD1, but not a transcriptionally active copy of the adjacent tuberous sclerosis gene, TSC2, as was present in the original TPK animals. These transgenic mice will clarify the importance of the TSC2 gene for normal expression of PKD1. Furthermore, they will show whether overexpressing just polycystin-1 is sufficient to cause a cystic phenotype. Subsequently, transgenic animals will be prepared with precisely defined copy numbers of functional PKD1. The phenotypic consequences and rescue potential of animals with different levels of PKD1 expression will be compared. The expression pattern, stability, phenotypic consequences and rescue potential of mutant PKD1 genes, with truncating, or motif specific in-frame or missense mutations, will also be assessed. These experiments will test the dominant negative potential of truncated polycystin-1 molecules. Furthermore, by examining the phenotypes associated with Pkd1-/- mice rescued, or partially rescued, by transgenes with motif specific mutations, the role of
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individual polycystin-1 domains will be elucidated. The second part of the proposal will test the function(s) of polycystin-1 during neonatal and adult life by creating conditional knockouts of Pkd1. The endogenous murine Pkd1 will be modified by insertion of LoxP sites flanking exon 1. Recombination to generate a null, Pkd1dell, allele will be induced by the addition of doxycycline after crossing with a transgenic mouse containing a Cre recombinase gene under the control of the Tet-On system. Cre expression will be activated for short periods during neonatal or adult life to examine the fate of null polycystin-1 cells in a viable animal. Cre recombination will further be directed to specific organs and/or tissues by placing the Tet-On system under the control of a tissue specific promoter, such as Ksp-cadherin, that is only expressed in the kidney. This system will allow temporal and spatial control of Pkd1 inactivation and allow the postdevelopmental role of polycystin-1 to be investigated in different organs and cell types. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •
Project Title: TREATING PERIODONTAL INFECTION: GLYCEMIC CONTROL Principal Investigator & Institution: Taylor, George W.; Professor; Cariology/Restor Sci/Endod; University of Michigan at Ann Arbor 3003 South State, Room 1040 Ann Arbor, Mi 481091274 Timing: Fiscal Year 2001; Project Start 15-SEP-2000; Project End 30-JUN-2003 Summary: There is compelling epidemiological and clinical evidence to suggest that periodontal infection adversely affects glycemic control in people with type 2 diabetes mellitus. The purpose of this project is to establish important preliminary data necessary to support design of a randomized clinical trail (RCT) to evaluate the effect of treating periodontal infection on glycemic control in type 2 diabetes. Accomplishing this goal will require conducting a pilot study involving treating periodontal infection to obtain estimates of changes and variablility of those changes in the established primary endpoint, hemoglobin A1c (HbA1c). This project will also provide an opportunity to explore use of several potential secondary endpoints including levels of periodontitisand glucose metabolism-related inflammatory mediators (TNFalphA,IL-1b, IL-6) and levels of serum cholesterol, triglyceride and lipids in patients with type 2 diabetes mellitus. The periodontal therapeutic regimen that will be evaluated will include ultrasonic bacterial curettage, local antimicrobial treatment with povidone-iodine irrigation, and oral systemic antibiotics (doxycycline or metronidizole). Prior to beginning the pilot treatment phase, we will characterize potentially eligible patients with type 2 diabetes who are registered in diabetes patient databases in the U-M Hospital and M-CARE (the U of M sponsored HMO) for inclusion in a sampling frame of 1,000 individuals that will be used to select and recruit subject for treatment of periodontal infection. Eligible and will subject will be identified and characterisized from this sample of 1000 via a detailed telephone interview. A sample of 135 of the telephone survey participants will participate in a screening examination session to identify 45 subject for the periodontal therapy phase. These subject will be treated and followed for 15 months. Results from this pilot project will be used as preliminary data to support design of an immediate follow-up proposal to NIH/NIDCR for funding an RCT to evaluate the effect of treating periodontal infection on glycemic control in type 2 diabetes. Results from this pilot project will be used as preliminary data to support design of an immediate follow-up proposal to NIH/NIDCR for funding an RCT to evaluate the effect of treating periodontal infection on glycemic control in type 2 diabetes. If results from the full scale clinical trail provide evidence that treating periodontal infection contributes to improved glycemic control, then diagnosis and
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treatment of periodontal infection in subject with NIDDM could be substantiated as an important component in management of NIDDM. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •
Project Title: TREATMENT OF ANEMIA USING AAV VECTORS Principal Investigator & Institution: Walker, Mark C.; Applied Genetic Technologies Corporation 12085 Research Dr, Ste 110 Alachua, Fl 32615 Timing: Fiscal Year 2001; Project Start 01-MAY-2001; Project End 31-OCT-2002 Summary: (applicant's abstract): The innovative use of AAV vector technology is proposed to develop milestones essential for the safe treatment of anemia secondary to chronic renal failure in cats. An A.AV-FeEPO vector has been constructed. The initial, in vitro, study will determine whether this vector can achieve FeEPO expression, and will also validate a HuEPO ELISA kit to measure FeEPO. This vector will then be administered IM to cats to investigate gene expression, in vivo. The transduced skeletal muscle will then be surgically excised to determine whether FeEPO expression is abolished. Transduction of tissues distant to the injection site will be determined by using PCR. Two studies will be performed to find the optimum method of FeEPO expression in feline patients with anemia. Firstly, AAV-FeEPO will be repeatedly administered at low doses to determine if this results in predictable incremental FeEPO expression. Finally, an AAV-FeEPO vector controlled by the Tet-On system will be constructed. Oral doxycycline will be administered at different doses (to demonstrate dose-dependent FeEPO expression) intermittently (to ascertain whether FeEPO expression can be "turned-on and off"). Cell mediated, and humoral immune responses against the vector will be measured in these cats. PROPOSED COMMERCIAL APPLICATION: Feline erythropoietin cDNA will be incorporated in an adenoassociated virus vector (AAV-FeEPO) and administered to cats with chronic renal failure and other types of erythropoietin responsive anemia. Expression of the feline erythropoietin cDNA will be controlled by a tetracycline regulatory element. This vector construct may be sold as a veterinary only pharmaceutical. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen
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Project Title: TROPHIC GENE TRANSFER IN MPTP ANIMALS Principal Investigator & Institution: Bankiewicz, Krys S.; Director; University of Rochester Orpa - Rc Box 270140 Rochester, Ny 14627 Timing: Fiscal Year 2002; Project Start 30-SEP-2002; Project End 31-AUG-2007 Summary: The long-term goal of this project is to apply neurotrophic factor gene therapy to patients with Parkinson's disease (PD). Extensive basic research in rodent and monkey models of PD indicates that the neurotrophic factor, glial cell ine-derived neurotrophic factor (GDNF) can slow the degeneration of dopamine (DA) neurons in the substantial nigra (SN); neurons that die in PD. Moreover, local delivery of these factors into the brain (using vector mediated gene transport) has shown protection of neurochemical, cellular and behavioral indices of DA function in 6-OHDA or MPTP lesioned animal models. Gene delivery was also shown to increase growth factor synthesis in a chronic manner within the vicinity of DA neurons; an advantage for treating slowly progressive CNS disorders such as PD. Thus, basic research strongly supports GDNF gene therapy as a novel treatment for PD. However, several issues require addressing prior to designing a clinical trial. First, identifying optimal vector system for gene delivery; this project will compare adeno-associated (AAV) and lentiviral vector systems which appear to be two most promising vector systems for
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transducing brain tissue. Secondly, it is not known whether GDNF gene delivery will ameliorate the parkinsonian condition in primates that have a stable, chronic lesion of the DA system. This project will use a primate model that closely reflects the mild clinical state of the disease. Thirdly, regulating gene expression will play an important role following therapeutic intervention to offset side-effects that may occur due to growth factor overexpression. Therefore, this revised project will evaluate adenoassociated viral (AAV) vectors in which the transgene can be regulated by peripheral doxycycline (Dox) administration. In summary, Dox regulated AAV and lentivral vectors will be produced and characterized in the rodent brain prior to initiating primate studies. High titer, helper-free clinical grade vectors prepared in a GLP facility will be used for primate studies. Vectors will be injected into the primate striatum using convection-enhanced delivery methods. Transgene expression and biological effects will be evaluated by a variety of behavioral, neurochemical, morphologic and molecular assays including, but not limited to in vivo FMT PET imaging, MRI, clinical rating and clinical responses to L-DOPA administration, HPLC, ELISA, in situ hybridization, immunocytochemistry, stereology and toxicology. These studies will involve collaborations within PDGTSG and will provide data leading to a clinical trial for Parkinson's disease. Results from these studies may also be applied for treating other neurodegenerative diseases and injuries related to the CNS. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •
Project Title: VIRUS INFECTION AND T CELL DIFFERENTIATION IN ASTHMA Principal Investigator & Institution: Ray, Anuradha; Professor; Medicine; University of Pittsburgh at Pittsburgh 350 Thackeray Hall Pittsburgh, Pa 15260 Timing: Fiscal Year 2001; Project Start 10-JUL-1998; Project End 30-JUN-2003 Summary: The relationship between virus infections and increased asthma flares in childhood is incompletely understood. It is now generally accepted that the predominant immune response in atopic asthma is mediated by T cells of the helper subtype (Th2). The following findings are important to note in the context of virus infections and asthmatic exacerbations in children: 1) An early pattern of transient Th2 response occurs in all neonates. This early Th2 bias eventually terminates in most individuals but persists in a significant fraction through adulthood. 2) Wheezing children over 2 years of age frequently have a combination of allergen- specific IgE (a Th2 response) and culture-proven virus infection. 3) In experimental animals, interleukin-4 (IL-4), a Th2-cell-derived cytokine, can convert cytotoxic CD8+T cells into non-toxic Th2-cytokine (IL-5) producing CD8+ T cells. We have recently established that the transcription factor GATA-3 plays a determinative role in Th2-specific gene expression. Also, in collaborative studies with us, Dr. Q. Hamid's group has demonstrated a significant increase in expression of GATA-3 mRNA colocalizing with IL-5 message in human asthmatic bronchoalveolar lavage (BAL) cells and biopsies compared to controls. Taken together, these observations lead us to hypothesize that: a) Viruses cause exacerbations of asthma by augmenting pre-existing Th2 responses through an increase in GATA-3 gene expression. b) Virus-induced increase in expression of the eosinophilic chemoattractant RANTES, which has been shown to activate T cells to trigger IL-5 production, also contributes to increased asthma flares during virus infections. To address this hypothesis we will: Aim I. Investigate the expression of GATA-3, T cell cytokine and RANTES mRNA in purified peripheral blood T cells of children by quantitative RT-PCR techniques. Aim II. Determine the consequence of T cell-specific expression of a dominant-negative mutant of GATA-3 on airway inflammation in mice using a doxycycline (dox)-inducible transgenic system
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recently established in our laboratory. These studies will determine whether inhibition of GATA-3 activity alone can abrogate Th2-like responses in vivo. Aim III. Determine the consequence of lung-specific inducible RANTES overexpression on T cell activation in vivo in transgenic mice. The effect of RANTES overexpression on GATA-3 and IL-5 gene expression will be investigated in T cells isolated from BAL cells and lung draining lymph nodes. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen
E-Journals: PubMed Central3 PubMed Central (PMC) is a digital archive of life sciences journal literature developed and managed by the National Center for Biotechnology Information (NCBI) at the U.S. National Library of Medicine (NLM).4 Access to this growing archive of e-journals is free and unrestricted.5 To search, go to http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=Pmc, and type “doxycycline” (or synonyms) into the search box. This search gives you access to full-text articles. The following is a sample of items found for doxycycline in the PubMed Central database: •
A search for doxycycline-dependent mutations that increase Drosophila melanogaster life span identifies the VhaSFD, Sugar baby, filamin, fwd and Cctl genes. by Landis GN, Bhole D, Tower J.; 2003; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=151307
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Comparison of cefuroxime axetil and doxycycline in treatment of patients with early Lyme disease associated with erythema migrans. by Luger SW, Paparone P, Wormser GP, Nadelman RB, Grunwaldt E, Gomez G, Wisniewski M, Collins JJ.; 1995 Mar; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&rendertype=exter nal&artid=162601
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Comparison of nested PCR with immunofluorescent-antibody assay for detection of Ehrlichia canis infection in dogs treated with doxycycline. by Wen B, Rikihisa Y, Mott JM, Greene R, Kim HY, Zhi N, Couto GC, Unver A, Bartsch R.; 1997 Jul; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&rendertype=abstr act&artid=229855
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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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Concentrations of doxycycline and penicillin G in sera and cerebrospinal fluid of patients treated for neuroborreliosis. by Karlsson M, Hammers S, Nilsson-Ehle I, Malmborg AS, Wretlind B.; 1996 May; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&rendertype=abstr act&artid=163273
3 4
Adapted from the National Library of Medicine: http://www.pubmedcentral.nih.gov/about/intro.html.
With PubMed Central, NCBI is taking the lead in preservation and maintenance of open access to electronic literature, just as NLM has done for decades with printed biomedical literature. PubMed Central aims to become a world-class library of the digital age. 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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Doxycycline control of prion protein transgene expression modulates prion disease in mice. by Tremblay P, Meiner Z, Galou M, Heinrich C, Petromilli C, Lisse T, Cayetano J, Torchia M, Mobley W, Bujard H, DeArmond SJ, Prusiner SB.; 1998 Oct 13; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=22873
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Doxycycline Hyclate Treatment of Experimental Canine Ehrlichiosis Followed by Challenge Inoculation with Two Ehrlichia canis Strains. by Breitschwerdt EB, Hegarty BC, Hancock SI.; 1998 Feb; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=105415
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Doxycycline Induces Expression of P Glycoprotein in MCF-7 Breast Carcinoma Cells. by Mealey KL, Barhoumi R, Burghardt RC, Safe S, Kochevar DT.; 2002 Mar; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=127468
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Doxycycline-induced expression of sense and inverted-repeat constructs modulates phosphogluconate mutase (Pgm) gene expression in adult Drosophila melanogaster. by Allikian MJ, Deckert-Cruz D, Rose MR, Landis GN, Tower J.; 2002; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=115223
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Doxycycline-Mediated Quantitative and Tissue-Specific Control of Gene Expression in Transgenic Mice. by Kistner A, Gossen M, Zimmermann F, Jerecic J, Ullmer C, Lubbert H, Bujard H.; 1996 Oct 1; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&rendertype=abstr act&artid=38261
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Doxycycline-rifampin versus doxycycline-streptomycin in treatment of human brucellosis due to Brucella melitensis. The GECMEI Group. Grupo de Estudio de Castilla-la Mancha de Enfermedades Infecciosas. by Solera J, Rodriguez-Zapata M, Geijo P, Largo J, Paulino J, Saez L, Martinez-Alfaro E, Sanchez L, Sepulveda MA, RuizRibo MD.; 1995 Sep; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&rendertype=abstr act&artid=162881
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Effects of penicillin, ceftriaxone, and doxycycline on morphology of Borrelia burgdorferi. by Kersten A, Poitschek C, Rauch S, Aberer E.; 1995 May; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&rendertype=abstr act&artid=162695
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Efficacy of Doxycycline, Azithromycin, or Trovafloxacin for Treatment of Experimental Rocky Mountain Spotted Fever in Dogs. by Breitschwerdt EB, Papich MG, Hegarty BC, Gilger B, Hancock SI, Davidson MG.; 1999 Apr; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=89211
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Efficacy of enrofloxacin or doxycycline for treatment of Bartonella henselae or Bartonella clarridgeiae infection in cats. by Kordick DL, Papich MG, Breitschwerdt EB.; 1997 Nov; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&rendertype=abstr act&artid=164143
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Eucaryotic cells protect Borrelia burgdorferi from the action of penicillin and ceftriaxone but not from the action of doxycycline and erythromycin. by Brouqui P, Badiaga S, Raoult D.; 1996 Jun; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&rendertype=abstr act&artid=163368
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In vitro activities of azithromycin and doxycycline against 15 isolates of Chlamydia pneumoniae. by Gnarpe J, Eriksson K, Gnarpe H.; 1996 Aug; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&rendertype=abstr act&artid=163427
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In vitro activities of doxycycline and enrofloxacin against European Chlamydia psittaci strains from turkeys. by Butaye P, Ducatelle R, De Backer P, Vermeersch H, Remon JP, Haesebrouck F.; 1997 Dec; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&rendertype=abstr act&artid=164215
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In Vitro Development of Resistance to Ofloxacin and Doxycycline in Bacillus anthracis Sterne. by Choe CH, Bouhaouala SS, Brook I, Elliott TB, Knudson GB.; 2000 Jun; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=89957
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In vitro effectiveness of azithromycin against doxycycline-resistant and -susceptible strains of Rickettsia tsutsugamushi, etiologic agent of scrub typhus. by Strickman D, Sheer T, Salata K, Hershey J, Dasch G, Kelly D, Kuschner R.; 1995 Nov; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&rendertype=abstr act&artid=162956
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In vitro evolution of a highly replicating, doxycycline-dependent HIV for applications in vaccine studies. by Marzio G, Verhoef K, Vink M, Berkhout B.; 2001 May 22; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=33470
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In Vitro Susceptibility of Coxiella burnetii to Linezolid in Comparison with Its Susceptibilities to Quinolones, Doxycycline, and Clarithromycin. by Gikas A, Spyridaki I, Scoulica E, Psaroulaki A, Tselentis Y.; 2001 Nov; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=90826
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In Vitro Susceptibility of Coxiella burnetii to Trovafloxacin in Comparison with Susceptibilities to Pefloxacin, Ciprofloxacin, Ofloxacin, Doxycycline, and Clarithromycin. by Gikas A, Spyridaki I, Psaroulaki A, Kofterithis D, Tselentis Y.; 1998 Oct; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=105931
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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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Long-term doxycycline-controlled expression of human tyrosine hydroxylase after direct adenovirus-mediated gene transfer to a rat model of Parkinson's disease. by Corti O, Sanchez-Capelo A, Colin P, Hanoun N, Hamon M, Mallet J.; 1999 Oct 12; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=18422
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Pharmacodynamic Interaction of Doxycycline and Artemisinin in Plasmodium falciparum. by Sponer U, Prajakwong S, Wiedermann G, Kollaritsch H, Wernsdorfer G, Wernsdorfer WH.; 2002 Jan; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=126969
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Prednisolone at anti-inflammatory or immunosuppressive dosages in conjunction with doxycycline does not potentiate the severity of Rickettsia rickettsii infection in
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dogs. by Breitschwerdt EB, Davidson MG, Hegarty BC, Papich MG, Grindem CB.; 1997 Jan; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&rendertype=abstr act&artid=163675 •
Quantitative PCR Assay To Evaluate Ampicillin, Ofloxacin, and Doxycycline for Treatment of Experimental Leptospirosis. by Truccolo J, Charavay F, Merien F, Perolat P.; 2002 Mar; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=127490
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Stringent doxycycline dependent control of CRE recombinase in vivo. by Schonig K, Schwenk F, Rajewsky K, Bujard H.; 2002 Dec 1; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=137989
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Therapeutic Effect of Doxycycline in Experimental Subclinical Canine Monocytic Ehrlichiosis: Evaluation of a 6-Week Course. by Harrus S, Waner T, Aizenberg I, Bark H.; 1998 Jul; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=105010
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Treatment of human brucellosis with doxycycline and gentamicin. by Solera J, Espinosa A, Martinez-Alfaro E, Sanchez L, Geijo P, Navarro E, Escribano J, Fernandez JA.; 1997 Jan; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&rendertype=exter nal&artid=163664
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Treatment of Vancomycin-Resistant Enterococcus faeciumwith RP 59500 (Quinupristin-Dalfopristin) Administered by Intermittent or Continuous Infusion, Alone or in Combination with Doxycycline, in an In Vitro Pharmacodynamic Infection Model with Simulated Endocardial Vegetations. by Aeschlimann JR, Zervos MJ, Rybak MJ.; 1998 Oct; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=105924
The National Library of Medicine: PubMed One of the quickest and most comprehensive ways to find academic studies in both English and other languages is to use PubMed, maintained by the National Library of Medicine.6 The advantage of PubMed over previously mentioned sources is that it covers a greater number of domestic and foreign references. It is also free to use. If the publisher has a Web site that offers full text of its journals, PubMed will provide links to that site, as well as to sites offering other related data. User registration, a subscription fee, or some other type of fee may be required to access the full text of articles in some journals. To generate your own bibliography of studies dealing with doxycycline, simply go to the PubMed Web site at http://www.ncbi.nlm.nih.gov/pubmed. Type “doxycycline” (or synonyms) into the search box, and click “Go.” The following is the type of output you can expect from PubMed for doxycycline (hyperlinks lead to article summaries):
6
PubMed was developed by the National Center for Biotechnology Information (NCBI) at the National Library of Medicine (NLM) at the National Institutes of Health (NIH). The PubMed database was developed in conjunction with publishers of biomedical literature as a search tool for accessing literature citations and linking to full-text journal articles at Web sites of participating publishers. Publishers that participate in PubMed supply NLM with their citations electronically prior to or at the time of publication.
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1-day azithromycin was as effective as 7-day doxycycline for nongonococcal urethritis syndrome in men. Author(s): Wendel TD. Source: Acp Journal Club. 1996 November-December; 125(3): 82. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=8912627&dopt=Abstract
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A comparative study of two different regimens of sparfloxacin versus doxycycline in the treatment of non-gonococcal urethritis in men. Author(s): Phillips I, Dimian C, Barlow D, Moi H, Stolz E, Weidner W, Perea E. Source: The Journal of Antimicrobial Chemotherapy. 1996 May; 37 Suppl A: 123-34. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=8737132&dopt=Abstract
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A comparison of chloramphenicol, trimethoprim-sulfamethoxazole, and doxycycline with doxycycline alone as maintenance therapy for melioidosis. Author(s): Chaowagul W, Simpson AJ, Suputtamongkol Y, Smith MD, Angus BJ, White NJ. Source: Clinical Infectious Diseases : an Official Publication of the Infectious Diseases Society of America. 1999 August; 29(2): 375-80. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10476745&dopt=Abstract
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A novel doxycycline inducible autoregulatory plasmid which displays “on”/”off” regulation suited to gene therapy applications. Author(s): Gould DJ, Berenstein M, Dreja H, Ledda F, Podhajcer OL, Chernajovsky Y. Source: Gene Therapy. 2000 December; 7(24): 2061-70. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11223986&dopt=Abstract
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A randomized clinical trial of prophylaxis for vacuum abortion: 3 versus 7 days of doxycycline. Author(s): Lichtenberg ES, Shott S. Source: Obstetrics and Gynecology. 2003 April; 101(4): 726-31. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12681877&dopt=Abstract
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A randomized comparison of indwelling pleural catheter and doxycycline pleurodesis in the management of malignant pleural effusions. Author(s): Putnam JB Jr, Light RW, Rodriguez RM, Ponn R, Olak J, Pollak JS, Lee RB, Payne DK, Graeber G, Kovitz KL. Source: Cancer. 1999 November 15; 86(10): 1992-9. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10570423&dopt=Abstract
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A randomized controlled trial of azithromycin versus doxycycline/ciprofloxacin for the syndromic management of sexually transmitted infections in a resource-poor setting. Author(s): Rustomjee R, Kharsany AB, Connolly CA, Karim SS. Source: The Journal of Antimicrobial Chemotherapy. 2002 May; 49(5): 875-8. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12003988&dopt=Abstract
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A single adenovirus vector mediates doxycycline-controlled expression of tyrosine hydroxylase in brain grafts of human neural progenitors. Author(s): Corti O, Sabate O, Horellou P, Colin P, Dumas S, Buchet D, Buc-Caron MH, Mallet J. Source: Nature Biotechnology. 1999 April; 17(4): 349-54. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10207882&dopt=Abstract
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Activation of recombinant human neutrophil procollagenase in the presence of doxycycline results in fragmentation of the enzyme and loss of enzyme activity. Author(s): Smith GN Jr, Brandt KD, Hasty KA. Source: Arthritis and Rheumatism. 1996 February; 39(2): 235-44. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=8849373&dopt=Abstract
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Activity of artemether-azithromycin versus artemether-doxycycline in the treatment of multiple drug resistant falciparum malaria. Author(s): Na-Bangchang K, Kanda T, Tipawangso P, Thanavibul A, Suprakob K, Ibrahim M, Wattanagoon Y, Karbwang J. Source: Southeast Asian J Trop Med Public Health. 1996 September; 27(3): 522-5. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=9185262&dopt=Abstract
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Acute respiratory failure after pleurodesis with doxycycline. Author(s): DiBardino DJ, Vanatta JM, Fagan SP, Awad SS. Source: The Annals of Thoracic Surgery. 2002 July; 74(1): 257-8. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12118779&dopt=Abstract
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Adjunctive benefits of subantimicrobial dose doxycycline in the management of severe, generalized, chronic periodontitis. Author(s): Novak MJ, Johns LP, Miller RC, Bradshaw MH. Source: J Periodontol. 2002 July; 73(7): 762-9. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12146536&dopt=Abstract
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Adjunctive treatment with subantimicrobial doses of doxycycline: effects on gingival fluid collagenase activity and attachment loss in adult periodontitis. Author(s): Golub LM, McNamara TF, Ryan ME, Kohut B, Blieden T, Payonk G, Sipos T, Baron HJ. Source: Journal of Clinical Periodontology. 2001 February; 28(2): 146-56. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11168739&dopt=Abstract
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Adverse effects of minocycline versus doxycycline in the treatment of Lyme neuroborreliosis. Author(s): Dotevall L, Hagberg L. Source: Clinical Infectious Diseases : an Official Publication of the Infectious Diseases Society of America. 2000 February; 30(2): 410-1. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10671363&dopt=Abstract
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alpha 1-Proteinase inhibitor in gingival crevicular fluid of humans with adult periodontitis: serpinolytic inhibition by doxycycline. Author(s): Lee HM, Golub LM, Chan D, Leung M, Schroeder K, Wolff M, Simon S, Crout R. Source: Journal of Periodontal Research. 1997 January; 32(1 Pt 1): 9-19. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=9085238&dopt=Abstract
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An open label comparative study of azithromycin and doxycycline in the treatment of non-gonococcal urethritis in males and Chlamydia trachomatis cervicitis in female sex workers in an STD clinic in Singapore. Author(s): Tan HH, Chan RK. Source: Singapore Med J. 1999 August; 40(8): 519-23. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10572491&dopt=Abstract
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An unusual presentation of doxycycline-induced photosensitivity. Author(s): Yong CK, Prendiville J, Peacock DL, Wong LT, Davidson AG. Source: Pediatrics. 2000 July; 106(1): E13. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10878182&dopt=Abstract
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Angioimmunoblastic lymphadenopathy with dysproteinemia following doxycycline administration. Author(s): Batinac T, Zamolo G, Jonjic N, Gruber F, Nacinovic A, Seili-Bekafigo I, Coklo M. Source: Tumori. 2003 January-February; 89(1): 91-5. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12729371&dopt=Abstract
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Antibiotics for prophylaxis of Plasmodium falciparum infections: in vitro activity of doxycycline against Senegalese isolates. Author(s): Pradines B, Spiegel A, Rogier C, Tall A, Mosnier J, Fusai T, Trape JF, Parzy D. Source: The American Journal of Tropical Medicine and Hygiene. 2000 January; 62(1): 82-5. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10761729&dopt=Abstract
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Anti-collagenolytic mechanism of action of doxycycline treatment in rheumatoid arthritis. Author(s): Nordstrom D, Lindy O, Lauhio A, Sorsa T, Santavirta S, Konttinen YT. Source: Rheumatology International. 1998; 17(5): 175-80. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=9542777&dopt=Abstract
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Atypical pneumonia in the Nordic countries: aetiology and clinical results of a trial comparing fleroxacin and doxycycline. Nordic Atypical Pneumonia Study Group. Author(s): Ragnar Norrby S. Source: The Journal of Antimicrobial Chemotherapy. 1997 April; 39(4): 499-508. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=9145823&dopt=Abstract
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Azithromycin and doxycycline in the treatment of female patients with acute urethral syndrome caused by Ureaplasma urealyticum: significance of duration of clinical symptoms. Author(s): Skerk V, Schonwald S, Krhen I, Rusinovic M, Strapac Z, Vukovic J. Source: Drugs Exp Clin Res. 2001; 27(4): 135-9. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11822223&dopt=Abstract
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Azithromycin monthly pulse vs daily doxycycline in the treatment of acne vulgaris. Author(s): Parsad D, Pandhi R, Nagpal R, Negi KS. Source: The Journal of Dermatology. 2001 January; 28(1): 1-4. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11280457&dopt=Abstract
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Azithromycin versus doxycycline for genital chlamydial infections: a meta-analysis of randomized clinical trials. Author(s): Lau CY, Qureshi AK. Source: Sexually Transmitted Diseases. 2002 September; 29(9): 497-502. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12218839&dopt=Abstract
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Azithromycin vs doxycycline in the treatment of inclusion conjunctivitis. Author(s): Katusic D, Petricek I, Mandic Z, Petric I, Salopek-Rabatic J, Kruzic V, Oreskovic K, Sikic J, Petricek G. Source: American Journal of Ophthalmology. 2003 April; 135(4): 447-51. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12654359&dopt=Abstract
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Azithromycin vs. doxycycline for Mediterranean spotted fever. Author(s): Meloni G, Meloni T. Source: The Pediatric Infectious Disease Journal. 1996 November; 15(11): 1042-4. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=8933556&dopt=Abstract
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Binding of doxycycline to keratin, melanin and human epidermal tissue. Author(s): Banning TP, Heard CM. Source: International Journal of Pharmaceutics. 2002 March 20; 235(1-2): 219-27. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11879756&dopt=Abstract
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Bleeding associated with doxycycline and warfarin treatment. Author(s): Baciewicz AM, Bal BS. Source: Archives of Internal Medicine. 2001 May 14; 161(9): 1231. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11343446&dopt=Abstract
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Can doxycycline cause polyneuropathy? Author(s): Olsson R. Source: Journal of Internal Medicine. 2002 April; 251(4): 361-2. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11952888&dopt=Abstract
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Carbazole as fluorescence carrier for preparation of doxycycline sensor. Author(s): Chen LX, Niu CG, Zeng GM, Huang GH, Shen GL, Yu RQ. Source: Anal Sci. 2003 February; 19(2): 295-8. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12608762&dopt=Abstract
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Ceftriaxone compared with doxycycline for the treatment of acute disseminated Lyme disease. Author(s): Dattwyler RJ, Luft BJ, Kunkel MJ, Finkel MF, Wormser GP, Rush TJ, Grunwaldt E, Agger WA, Franklin M, Oswald D, Cockey L, Maladorno D. Source: The New England Journal of Medicine. 1997 July 31; 337(5): 289-94. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=9233865&dopt=Abstract
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Chemical pleurodesis with doxycycline 1 g. Author(s): Herrington JD, Gora-Harper ML, Salley RK. Source: Pharmacotherapy. 1996 March-April; 16(2): 280-5. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=8820473&dopt=Abstract
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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:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11054656&dopt=Abstract
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Chlamydial cervicitis and urethritis: single dose treatment compared with doxycycline for seven days in community based practises. Author(s): Thorpe EM Jr, Stamm WE, Hook EW 3rd, Gall SA, Jones RB, Henry K, Whitworth G, Johnson RB. Source: Genitourinary Medicine. 1996 April; 72(2): 93-7. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=8698374&dopt=Abstract
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Chloroquine bioassay of plasma specimens obtained from soldiers on chloroquine plus doxycycline for malaria prophylaxis. Author(s): Kotecka BM, Edstein MD, Rieckmann KH. Source: International Journal for Parasitology. 1996 November; 26(11): 1325-9. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=9024880&dopt=Abstract
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Chloroquine/doxycycline combination versus chloroquine alone, and doxycycline alone for the treatment of Plasmodium falciparum and Plasmodium vivax malaria in northeastern Irian Jaya, Indonesia. Author(s): Taylor WR, Widjaja H, Richie TL, Basri H, Ohrt C, Tjitra, Taufik E, Jones TR, Kain KC, Hoffman SL. Source: The American Journal of Tropical Medicine and Hygiene. 2001 May-June; 64(56): 223-8. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11463107&dopt=Abstract
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Chronic intoxication by doxycycline use for more than 12 years. Author(s): Westermann GW, Bohm M, Bonsmann G, Rahn KH, Kisters K. Source: Journal of Internal Medicine. 1999 December; 246(6): 591-2. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10620103&dopt=Abstract
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Ciprofloxacin and rifampicin versus doxycycline and rifampicin in the treatment of brucellosis. Author(s): Agalar C, Usubutun S, Turkyilmaz R. Source: European Journal of Clinical Microbiology & Infectious Diseases : Official Publication of the European Society of Clinical Microbiology. 1999 August; 18(8): 535-8. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10517189&dopt=Abstract
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Clarithromycin versus doxycycline in the treatment of rosacea. Author(s): Torresani C, Pavesi A, Manara GC. Source: International Journal of Dermatology. 1997 December; 36(12): 942-6. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=9466207&dopt=Abstract
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Clinical evaluation of systemic doxycycline and ibuprofen administration as an adjunctive treatment for adult periodontitis. Author(s): Ng VW, Bissada NF. Source: J Periodontol. 1998 July; 69(7): 772-6. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=9706854&dopt=Abstract
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Collagenase-2 and -3 are inhibited by doxycycline in the chronically inflamed lung in bronchiectasis. Author(s): Sepper R, Prikk K, Tervahartiala T, Konttinen YT, Maisi P, Lopes-Otin C, Sorsa T. Source: Annals of the New York Academy of Sciences. 1999 June 30; 878: 683-5. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10415807&dopt=Abstract
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Comparative analysis of azithromycin and doxycycline efficacy in the treatment of female patients with acute urethral syndrome caused by Ureaplasma urealyticum. Author(s): Skerk V, Barsic B, Car V, Schonwald S, Klinar I. Source: Journal of Chemotherapy (Florence, Italy). 2000 April; 12(2): 186-8. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10789560&dopt=Abstract
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Comparative in-vitro activity of levofloxacin, other fluoroquinolones, doxycycline and erythromycin against Ureaplasma urealyticum and Mycoplasma hominis. Author(s): Ullmann U, Schubert S, Krausse R. Source: The Journal of Antimicrobial Chemotherapy. 1999 June; 43 Suppl C: 33-6. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10404335&dopt=Abstract
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Comparative safety of tetracycline, minocycline, and doxycycline. Author(s): Shapiro LE, Knowles SR, Shear NH. Source: Archives of Dermatology. 1997 October; 133(10): 1224-30. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=9382560&dopt=Abstract
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Comparison of azithromycin and doxycycline in the treatment of erythema migrans. Author(s): Barsic B, Maretic T, Majerus L, Strugar J. Source: Infection. 2000 May-June; 28(3): 153-6. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10879639&dopt=Abstract
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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:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12234839&dopt=Abstract
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Compliance with doxycycline therapy in sexually transmitted diseases clinics. Author(s): Augenbraun M, Bachmann L, Wallace T, Dubouchet L, McCormack W, Hook EW 3rd. Source: Sexually Transmitted Diseases. 1998 January; 25(1): 1-4. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=9437776&dopt=Abstract
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Concentrations of doxycycline and penicillin G in sera and cerebrospinal fluid of patients treated for neuroborreliosis. Author(s): Karlsson M, Hammers S, Nilsson-Ehle I, Malmborg AS, Wretlind B. Source: Antimicrobial Agents and Chemotherapy. 1996 May; 40(5): 1104-7. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=8723448&dopt=Abstract
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Construction of an rtTA2(s)-m2/tts(kid)-based transcription regulatory switch that displays no basal activity, good inducibility, and high responsiveness to doxycycline in mice and non-human primates. Author(s): Lamartina S, Silvi L, Roscilli G, Casimiro D, Simon AJ, Davies ME, Shiver JW, Rinaudo CD, Zampaglione I, Fattori E, Colloca S, Gonzalez Paz O, Laufer R, Bujard H, Cortese R, Ciliberto G, Toniatti C. Source: Molecular Therapy : the Journal of the American Society of Gene Therapy. 2003 February; 7(2): 271-80. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12597916&dopt=Abstract
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Control of erythropoietin delivery by doxycycline in mice after intramuscular injection of adeno-associated vector. Author(s): Bohl D, Salvetti A, Moullier P, Heard JM. Source: Blood. 1998 September 1; 92(5): 1512-7. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=9716577&dopt=Abstract
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Cutaneous hyperpigmentation induced by doxycycline: histochemical and ultrastructural examination, laser microprobe mass analysis, and cathodoluminescence. Author(s): Bohm M, Schmidt PF, Lodding B, Uphoff H, Westermann G, Luger TA, Bonsmann G, Metze D. Source: The American Journal of Dermatopathology. 2002 August; 24(4): 345-50. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12142617&dopt=Abstract
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Daily oral grepafloxacin vs. twice daily oral doxycycline in the treatment of Chlamydia trachomatis endocervical infection. Author(s): McCormack WM, Martin DH, Hook EW 3rd, Jones RB. Source: Infectious Diseases in Obstetrics and Gynecology. 1998; 6(3): 109-15. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=9785106&dopt=Abstract
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Depletion of wolbachia endobacteria in Onchocerca volvulus by doxycycline and microfilaridermia after ivermectin treatment. Author(s): Hoerauf A, Mand S, Adjei O, Fleischer B, Buttner DW. Source: Lancet. 2001 May 5; 357(9266): 1415-6. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11356444&dopt=Abstract
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Differential patterns of response to doxycycline and transforming growth factor beta1 in the down-regulation of collagenases in osteoarthritic and normal human chondrocytes. Author(s): Shlopov BV, Smith GN Jr, Cole AA, Hasty KA. Source: Arthritis and Rheumatism. 1999 April; 42(4): 719-27. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10211886&dopt=Abstract
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Dose-dependent doxycycline-mediated adrenocorticotropic hormone secretion from encapsulated Tet-on proopiomelanocortin Neuro2A cells in the subarachnoid space. Author(s): Saitoh Y, Eguchi Y, Hagihara Y, Arita N, Watahiki M, Tsujimoto Y, Hayakawa T. Source: Human Gene Therapy. 1998 May 1; 9(7): 997-1002. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=9607411&dopt=Abstract
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Double-blind comparison of trovafloxacin and doxycycline in the treatment of uncomplicated Chlamydial urethritis and cervicitis. Trovafloxacin Chlamydial Urethritis/Cervicitis Study Group. Author(s): McCormack WM, Dalu ZA, Martin DH, Hook EW 3rd, Laisi R, Kell P, Pluck ND, Johnson RB. Source: Sexually Transmitted Diseases. 1999 October; 26(9): 531-6. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10534208&dopt=Abstract
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Doxycycline and azithromycin for prevention of chlamydial persistence or recurrence one month after treatment in women. A use-effectiveness study in public health settings. Author(s): Hillis SD, Coles FB, Litchfield B, Black CM, Mojica B, Schmitt K, St Louis ME. Source: Sexually Transmitted Diseases. 1998 January; 25(1): 5-11. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=9437777&dopt=Abstract
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Doxycycline and chloroquine as treatment for chronic Q fever endocarditis. Author(s): Calza L, Attard L, Manfredi R, Chiodo F. Source: The Journal of Infection. 2002 August; 45(2): 127-9. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12217721&dopt=Abstract
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Doxycycline and community-acquired pneumonia. Author(s): Woolley RJ. Source: American Family Physician. 1998 February 1; 57(3): 426-7. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=9475892&dopt=Abstract
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Doxycycline and eradication of microfilaremia in patients with loiasis. Author(s): Brouqui P, Fournier PE, Raoult D. Source: Emerging Infectious Diseases. 2001; 7(3 Suppl): 604-5. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11485684&dopt=Abstract
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Doxycycline and rifampicin for mild scrub-typhus infections in northern Thailand: a randomised trial. Author(s): Watt G, Kantipong P, Jongsakul K, Watcharapichat P, Phulsuksombati D, Strickman D. Source: Lancet. 2000 September 23; 356(9235): 1057-61. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11009140&dopt=Abstract
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Doxycycline and staining of permanent teeth. Author(s): Lochary ME, Lockhart PB, Williams WT Jr. Source: The Pediatric Infectious Disease Journal. 1998 May; 17(5): 429-31. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=9613662&dopt=Abstract
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Doxycycline as first line malarial prophylaxis: how safe is it? Author(s): Schuhwerk M, Behrens RH. Source: Journal of Travel Medicine : Official Publication of the International Society of Travel Medicine and the Asia Pacific Travel Health Association. 1998 June; 5(2): 102. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=9772326&dopt=Abstract
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Doxycycline compared with azithromycin for treating women with genital Chlamydia trachomatis infections: an incremental cost-effectiveness analysis. Author(s): Magid D, Douglas JM Jr, Schwartz JS. Source: Annals of Internal Medicine. 1996 February 15; 124(4): 389-99. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=8554247&dopt=Abstract
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Doxycycline decreases tumor burden in a bone metastasis model of human breast cancer. Author(s): Duivenvoorden WC, Popovic SV, Lhotak S, Seidlitz E, Hirte HW, Tozer RG, Singh G. Source: Cancer Research. 2002 March 15; 62(6): 1588-91. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11912125&dopt=Abstract
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Doxycycline dosing. Author(s): Caton JG, Ciancio S, Ryan M, Golub L, Blieden T, Thomas J, Walker C. Source: The Journal of the American Dental Association. 2001 October; 132(10): 1366, 1368, 1370. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11680351&dopt=Abstract
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Doxycycline for community-acquired pneumonia. Author(s): Cunha BA. Source: Clinical Infectious Diseases : an Official Publication of the Infectious Diseases Society of America. 2003 September 15; 37(6): 870. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12955665&dopt=Abstract
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Doxycycline for tick bites--not for everyone. Author(s): Shapiro ED. Source: The New England Journal of Medicine. 2001 July 12; 345(2): 133-4. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11450662&dopt=Abstract
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Doxycycline for treatment of community-acquired pneumonia. Author(s): Johnson JR. Source: Clinical Infectious Diseases : an Official Publication of the Infectious Diseases Society of America. 2002 September 1; 35(5): 632; Author Reply 632-3. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12173142&dopt=Abstract
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Doxycycline in community acquired respiratory infections--a perspective of 1990's. Author(s): Mahashur AA, Jaguste V. Source: J Assoc Physicians India. 1999 March; 47(3): 326-31. Review. No Abstract Available. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10999130&dopt=Abstract
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Doxycycline in patients with abdominal aortic aneurysms and in mice: comparison of serum levels and effect on aneurysm growth in mice. Author(s): Prall AK, Longo GM, Mayhan WG, Waltke EA, Fleckten B, Thompson RW, Baxter BT. Source: Journal of Vascular Surgery : Official Publication, the Society for Vascular Surgery [and] International Society for Cardiovascular Surgery, North American Chapter. 2002 May; 35(5): 923-9. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12021708&dopt=Abstract
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Doxycycline in the treatment of human onchocerciasis: Kinetics of Wolbachia endobacteria reduction and of inhibition of embryogenesis in female Onchocerca worms. Author(s): Hoerauf A, Mand S, Volkmann L, Buttner M, Marfo-Debrekyei Y, Taylor M, Adjei O, Buttner DW. Source: Microbes and Infection / Institut Pasteur. 2003 April; 5(4): 261-73. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12706439&dopt=Abstract
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Doxycycline in the treatment of rheumatoid arthritis--a pilot study. Author(s): Sreekanth VR, Handa R, Wali JP, Aggarwal P, Dwivedi SN. Source: J Assoc Physicians India. 2000 August; 48(8): 804-7. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11273473&dopt=Abstract
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Doxycycline induced intracranial hypertension. Author(s): Lochhead J, Elston JS. Source: Bmj (Clinical Research Ed.). 2003 March 22; 326(7390): 641-2. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12649241&dopt=Abstract
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Doxycycline induces apoptosis by way of caspase-3 activation with inhibition of matrix metalloproteinase in human T-lymphoblastic leukemia CCRF-CEM cells. Author(s): Iwasaki H, Inoue H, Mitsuke Y, Badran A, Ikegaya S, Ueda T. Source: The Journal of Laboratory and Clinical Medicine. 2002 December; 140(6): 382-6. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12486404&dopt=Abstract
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Doxycycline induces expression of P glycoprotein in MCF-7 breast carcinoma cells. Author(s): Mealey KL, Barhoumi R, Burghardt RC, Safe S, Kochevar DT. Source: Antimicrobial Agents and Chemotherapy. 2002 March; 46(3): 755-61. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11850258&dopt=Abstract
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Doxycycline induces Fas/Fas ligand-mediated apoptosis in Jurkat T lymphocytes. Author(s): Liu J, Kuszynski CA, Baxter BT. Source: Biochemical and Biophysical Research Communications. 1999 July 5; 260(2): 5627. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10403806&dopt=Abstract
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Doxycycline inhibition of interleukin-1 in the corneal epithelium. Author(s): Solomon A, Rosenblatt M, Li DQ, Liu Z, Monroy D, Ji Z, Lokeshwar BL, Pflugfelder SC. Source: Investigative Ophthalmology & Visual Science. 2000 August; 41(9): 2544-57. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10937565&dopt=Abstract
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Doxycycline inhibits bone resorption by human interface membrane cells from aseptically loose hip replacements. Author(s): Ong SM, Taylor GJ. Source: The Journal of Bone and Joint Surgery. British Volume. 2003 April; 85(3): 456-61. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12729128&dopt=Abstract
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Doxycycline is a cost-effective therapy for hospitalized patients with communityacquired pneumonia. Author(s): Ailani RK, Agastya G, Ailani RK, Mukunda BN, Shekar R. Source: Archives of Internal Medicine. 1999 February 8; 159(3): 266-70. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=9989538&dopt=Abstract
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Doxycycline re-revisited. Author(s): Cunha BA. Source: Archives of Internal Medicine. 1999 May 10; 159(9): 1006-7. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10326943&dopt=Abstract
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Doxycycline revisited. Author(s): Joshi N, Miller DQ. Source: Archives of Internal Medicine. 1997 July 14; 157(13): 1421-8. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=9224219&dopt=Abstract
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Doxycycline revisited: an old medicine for emerging diseases. Author(s): Horowitz HW, Wormser GP. Source: Archives of Internal Medicine. 1998 January 26; 158(2): 192-3. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=9448562&dopt=Abstract
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Doxycycline sclerosis of benign lymphoepithelial cysts in patients infected with HIV. Author(s): Lustig LR, Lee KC, Murr A, Deschler D, Kingdom T. Source: The Laryngoscope. 1998 August; 108(8 Pt 1): 1199-205. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=9707244&dopt=Abstract
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Doxycycline sclerotherapy of benign lymphoepithelial cysts of the parotid: a minimally invasive treatment. Author(s): Suskind DL, Tavill MA, Handler SD. Source: International Journal of Pediatric Otorhinolaryngology. 2000 April 15; 52(2): 15761. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10767463&dopt=Abstract
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Doxycycline sensitivity of S. pneumoniae isolates. Author(s): Lederman ER, Gleeson TD, Driscoll T, Wallace MR. Source: Clinical Infectious Diseases : an Official Publication of the Infectious Diseases Society of America. 2003 April 15; 36(8): 1091. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12684932&dopt=Abstract
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Doxycycline treatment of groin lymphatic fistulae following arterial reconstruction procedures. Author(s): Cnotliwy M, Gutowski P, Petriczko W, Turowski R. Source: European Journal of Vascular and Endovascular Surgery : the Official Journal of the European Society for Vascular Surgery. 2001 May; 21(5): 469-70. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11352526&dopt=Abstract
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Doxycycline use for rickettsial disease in pediatric patients. Author(s): Purvis JJ, Edwards MS. Source: The Pediatric Infectious Disease Journal. 2000 September; 19(9): 871-4. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11001111&dopt=Abstract
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Doxycycline vs mefloquine. Author(s): Bohnker BK. Source: Military Medicine. 1997 April; 162(4): I, Iv. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=9110542&dopt=Abstract
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Doxycycline vs. mefloquine. Author(s): Conrad KA, Kiser WR. Source: Military Medicine. 1997 January; 162(1): Viii. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=9002694&dopt=Abstract
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Doxycycline: new ways to use an old antibiotic. Author(s): Tice AD. Source: Archives of Internal Medicine. 1998 April 27; 158(8): 928-9. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=9570183&dopt=Abstract
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Doxycycline-induced esophageal ulceration in the U.S. Military service. Author(s): Morris TJ, Davis TP. Source: Military Medicine. 2000 April; 165(4): 316-9. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10803009&dopt=Abstract
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Doxycycline-induced esophageal ulceration. Author(s): Isler M. Source: Military Medicine. 2001 March; 166(3): 203, 222. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11263018&dopt=Abstract
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Doxycycline-induced hypoglycemia in a nondiabetic young man. Author(s): Basaria S, Braga M, Moore WT. Source: Southern Medical Journal. 2002 November; 95(11): 1353-4. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12540009&dopt=Abstract
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Doxycycline-induced hypoglycemia. Author(s): Odeh M, Oliven A. Source: Journal of Clinical Pharmacology. 2000 October; 40(10): 1173-4. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11028257&dopt=Abstract
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Doxycycline-induced inhibition of prolidase activity in human skin fibroblasts and its involvement in impaired collagen biosynthesis. Author(s): Karna E, Palka J, Wolczynski S. Source: European Journal of Pharmacology. 2001 October 26; 430(1): 25-31. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11698059&dopt=Abstract
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Doxycycline-induced lithium toxicity. Author(s): Miller SC. Source: Journal of Clinical Psychopharmacology. 1997 February; 17(1): 54-5. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=9004058&dopt=Abstract
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Doxycycline-inducible expression of SPARC/Osteonectin/BM40 in MDA-MB-231 human breast cancer cells results in growth inhibition. Author(s): Dhanesuan N, Sharp JA, Blick T, Price JT, Thompson EW. Source: Breast Cancer Research and Treatment. 2002 September; 75(1): 73-85. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12500936&dopt=Abstract
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Doxycycline-inducible retroviral expression of green fluorescent protein in immortalized human keratinocytes. Author(s): Gill PS, Krueger GG, Kohan DE. Source: Experimental Dermatology. 2002 June; 11(3): 266-74. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12102666&dopt=Abstract
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Doxycycline-regulated lentiviral vector system with a novel reverse transactivator rtTA2S-M2 shows a tight control of gene expression in vitro and in vivo. Author(s): Koponen JK, Kankkonen H, Kannasto J, Wirth T, Hillen W, Bujard H, YlaHerttuala S. Source: Gene Therapy. 2003 March; 10(6): 459-66. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12621450&dopt=Abstract
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Duration of clinical symptoms in female patients with acute urethral syndrome caused by Chlamydia trachomatis treated with azithromycin or doxycycline. Author(s): Skerk V, Schonwald S, Strapac Z, Beus A, Francetic I, Krhen I, Lesko V, Vukovic J. Source: Journal of Chemotherapy (Florence, Italy). 2001 April; 13(2): 176-81. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11330365&dopt=Abstract
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Duration of clinical symptoms in female patients with acute urethral syndrome caused by Ureaplasma urealyticum treated with azithromycin or doxycycline. Author(s): Skerk V, Schonwald S, Strapac Z, Beus A, Francetic I, Krhen I, Lesko V, Vukovic J. Source: Journal of Chemotherapy (Florence, Italy). 2000 December; 12(6): 533-5. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11154040&dopt=Abstract
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Effect of doxycycline on the apical seal of retrograde filling materials. Author(s): Barkhordar RA, Russel T. Source: J Calif Dent Assoc. 1998 November; 26(11): 842-5. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10029779&dopt=Abstract
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Effect of minocycline and doxycycline on IgE responses. Author(s): Smith-Norowitz TA, Bluth MH, Drew H, Norowitz KB, Chice S, Shah VN, Nowakowski M, Josephson AS, Durkin HG, Joks R. Source: Annals of Allergy, Asthma & Immunology : Official Publication of the American College of Allergy, Asthma, & Immunology. 2002 August; 89(2): 172-9. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12197574&dopt=Abstract
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Effects of cationic liposome-encapsulated doxycycline on experimental Chlamydia trachomatis genital infection in mice. Author(s): Sangare L, Morisset R, Gaboury L, Ravaoarinoro M. Source: The Journal of Antimicrobial Chemotherapy. 2001 March; 47(3): 323-31. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11222565&dopt=Abstract
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Effects of doxycycline on cancer cells in vitro and in vivo. Author(s): Fife RS, Sledge GW Jr. Source: Advances in Dental Research. 1998 November; 12(2): 94-6. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=9972129&dopt=Abstract
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Effects of doxycycline on human prostate cancer cells in vitro. Author(s): Fife RS, Sledge GW Jr, Roth BJ, Proctor C. Source: Cancer Letters. 1998 May 15; 127(1-2): 37-41. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=9619856&dopt=Abstract
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Effects of smoking on local delivery of controlled-release doxycycline as compared to scaling and root planing. Author(s): Ryder MI, Pons B, Adams D, Beiswanger B, Blanco V, Bogle G, Donly K, Hallmon W, Hancock EB, Hanes P, Hawley C, Johnson L, Wang HL, Wolinsky L, Yukna R, Polson A, Carron G, Garrett S. Source: Journal of Clinical Periodontology. 1999 October; 26(10): 683-91. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10522780&dopt=Abstract
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Effects of subantimicrobial-dose doxycycline in the treatment of moderate acne. Author(s): Skidmore R, Kovach R, Walker C, Thomas J, Bradshaw M, Leyden J, Powala C, Ashley R. Source: Archives of Dermatology. 2003 April; 139(4): 459-64. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12707093&dopt=Abstract
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Effects of tiaprofenic acid on urinary pyridinium crosslinks in adjuvant arthritic rats: comparison with doxycycline. Author(s): Weithmann KU, Schlotte V, Jeske V, Seiffge D, Laber A, Haase B, Schleyerbach R. Source: Inflammation Research : Official Journal of the European Histamine Research Society. [et Al.]. 1997 July; 46(7): 246-52. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=9266272&dopt=Abstract
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Effects on the clinical indices and gingival crevicular fluid enzyme activities of the cyclical regimen of low-dose doxycycline therapy for adult periodontitis. Author(s): Alptekin NO, Kurtoglu F, Serpek B, Duran I, Gozlu M. Source: J Int Acad Periodontol. 2000 January; 2(1): 3-8. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12666979&dopt=Abstract
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Efficacy of daily antimalarial chemoprophylaxis in tropical Africa using either doxycycline or chloroquine-proguanil; a study conducted in 1996 in the French Army. Author(s): Baudon D, Martet G, Pascal B, Bernard J, Keundjian A, Laroche R. Source: Trans R Soc Trop Med Hyg. 1999 May-June; 93(3): 302-3. No Abstract Available. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10492765&dopt=Abstract
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Efficacy of doxycycline in a goat model of Pasteurella pneumonia. Author(s): Ole-Mapenay IM, Mitema ES. Source: J S Afr Vet Assoc. 1997 June; 68(2): 55-8. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=9291074&dopt=Abstract
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Efficacy of norfloxacin and doxycycline for treatment of vibrio cholerae 0139 infection. Author(s): Dutta D, Bhattacharya SK, Bhattacharya MK, Deb A, Deb M, Manna B, Moitra A, Mukhopadhyay AK, Nair GB. Source: The Journal of Antimicrobial Chemotherapy. 1996 March; 37(3): 575-81. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=9182114&dopt=Abstract
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Efficacy of subantimicrobial dosing with doxycycline. Point/counterpoint. Author(s): Greenstein G, Lamster I. Source: The Journal of the American Dental Association. 2001 April; 132(4): 457-66. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11315376&dopt=Abstract
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Ehrlichiosis--ticks, dogs, and doxycycline. Author(s): Goodman JL. Source: The New England Journal of Medicine. 1999 July 15; 341(3): 195-7. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10403860&dopt=Abstract
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Esophageal ulceration complicating doxycycline therapy. Author(s): Al-Mofarreh MA, Al Mofleh IA. Source: World Journal of Gastroenterology : Wjg. 2003 March; 9(3): 609-11. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12632529&dopt=Abstract
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Establishment of an artificial beta-cell line expressing insulin under the control of doxycycline. Author(s): Qin XY, Shen KT, Zhang X, Cheng ZH, Xu XR, Han ZG. Source: World Journal of Gastroenterology : Wjg. 2002 April; 8(2): 367-70. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11925627&dopt=Abstract
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F9 embryonal carcinoma cells engineered for tamoxifen-dependent Cre-mediated sitedirected mutagenesis and doxycycline-inducible gene expression. Author(s): Chiba H, Chambon P, Metzger D. Source: Experimental Cell Research. 2000 November 1; 260(2): 334-9. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11035928&dopt=Abstract
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Fixed drug eruption due to doxycycline and metronidazole. Author(s): Walfish AE, Sapadin AN. Source: Cutis; Cutaneous Medicine for the Practitioner. 2002 March; 69(3): 207-8. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11926340&dopt=Abstract
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Fluorescence spectrum analysis of atherosclerotic plaque using doxycycline. Author(s): Miyagi M, Nakajima H, Katoh T, Usui M, Amemiya T, Nagai Y, Ibukiyama C. Source: Japanese Circulation Journal. 1999 May; 63(5): 379-86. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10943618&dopt=Abstract
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Follow-up of patients treated with oral doxycycline for Lyme neuroborreliosis. Author(s): Karkkonen K, Stiernstedt SH, Karlsson M. Source: Scandinavian Journal of Infectious Diseases. 2001; 33(4): 259-62. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11345216&dopt=Abstract
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Genital fixed drug eruption: cross-reactivity between doxycycline and minocycline. Author(s): Correia O, Delgado L, Polonia J. Source: Clinical and Experimental Dermatology. 1999 March; 24(2): 137. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10447381&dopt=Abstract
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High-dose methotrexate-doxycycline interaction. Author(s): Tortajada-Ituren JJ, Ordovas-Baines JP, Llopis-Salvia P, Jimenez-Torres NV. Source: The Annals of Pharmacotherapy. 1999 July-August; 33(7-8): 804-8. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10466909&dopt=Abstract
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High-level ultraviolet A photoprotection is needed to prevent doxycycline phototoxicity: lessons learned in East Timor. Author(s): Lim DS, Murphy GM. Source: The British Journal of Dermatology. 2003 July; 149(1): 213-4. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12890230&dopt=Abstract
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Highly suppressible expression of single-chain interleukin-12 by doxycycline following adenoviral infection with a single-vector Tet-regulatory system. Author(s): Block A, Puls F, Muller J, Milasinovic D, Igelmann D, Schafer P, Kupfermann N, Schmoldt A, Ameis D, Greten H. Source: The Journal of Gene Medicine. 2003 March; 5(3): 190-200. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12666185&dopt=Abstract
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Histologic effect of doxycycline sclerotherapy on rat femoral nerve. Author(s): Kirse DJ, Suen JY, Stern SJ, Schaefer RF, Roberson PK. Source: Head & Neck. 1996 November-December; 18(6): 506-11. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=8902563&dopt=Abstract
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Hydrosalpinx treated with extended doxycycline does not compromise the success of in vitro fertilization. Author(s): Hurst BS, Tucker KE, Awoniyi CA, Schlaff WD. Source: Fertility and Sterility. 2001 May; 75(5): 1017-9. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11334919&dopt=Abstract
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In vitro activities of azithromycin and doxycycline against 15 isolates of Chlamydia pneumoniae. Author(s): Gnarpe J, Eriksson K, Gnarpe H. Source: Antimicrobial Agents and Chemotherapy. 1996 August; 40(8): 1843-5. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=8843291&dopt=Abstract
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In vitro dermal and transdermal delivery of doxycycline from ethanol/migliol 840 vehicles. Author(s): Perkins NC, Heard CM. Source: International Journal of Pharmaceutics. 1999 November 15; 190(2): 155-64. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10547455&dopt=Abstract
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In vitro evolution of a highly replicating, doxycycline-dependent HIV for applications in vaccine studies. Author(s): Marzio G, Verhoef K, Vink M, Berkhout B. Source: Proceedings of the National Academy of Sciences of the United States of America. 2001 May 22; 98(11): 6342-7. Epub 2001 May 15. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11353837&dopt=Abstract
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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:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10052911&dopt=Abstract
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Inhibition of mesothelioma cell growth in vitro by doxycycline. Author(s): Rubins JB, Charboneau D, Alter MD, Bitterman PB, Kratzke RA. Source: The Journal of Laboratory and Clinical Medicine. 2001 August; 138(2): 101-6. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11477376&dopt=Abstract
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Inhibition of MMP synthesis by doxycycline and chemically modified tetracyclines (CMTs) in human endothelial cells. Author(s): Hanemaaijer R, Visser H, Koolwijk P, Sorsa T, Salo T, Golub LM, van Hinsbergh VW. Source: Advances in Dental Research. 1998 November; 12(2): 114-8. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=9972133&dopt=Abstract
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Inhibition of proliferation and induction of apoptosis by doxycycline in cultured human osteosarcoma cells. Author(s): Fife RS, Rougraff BT, Proctor C, Sledge GW Jr. Source: The Journal of Laboratory and Clinical Medicine. 1997 November; 130(5): 530-4. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=9390641&dopt=Abstract
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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:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11846203&dopt=Abstract
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Inhibition of recombinant human neutrophil collagenase by doxycycline is pH dependent. Author(s): Smith GN Jr, Brandt KD, Mickler EA, Hasty KA. Source: The Journal of Rheumatology. 1997 September; 24(9): 1769-73. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=9292802&dopt=Abstract
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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:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10403420&dopt=Abstract
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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:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10221884&dopt=Abstract
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Lack of effect of doxycycline on disease activity and joint damage in patients with rheumatoid arthritis. A double blind, placebo controlled trial. Author(s): van der Laan W, Molenaar E, Ronday K, Verheijen J, Breedveld F, Greenwald R, Dijkmans B, TeKoppele J. Source: The Journal of Rheumatology. 2001 September; 28(9): 1967-74. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11550961&dopt=Abstract
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Lack of efficacy of oral bacitracin plus doxycycline for the eradication of stool colonization with vancomycin-resistant Enterococcus faecium. Author(s): Weinstein MR, Dedier H, Brunton J, Campbell I, Conly JM. Source: Clinical Infectious Diseases : an Official Publication of the Infectious Diseases Society of America. 1999 August; 29(2): 361-6. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10476743&dopt=Abstract
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Local delivery of doxycycline for the treatment of periodontitis. Author(s): Garrett S. Source: Compend Contin Educ Dent. 1999 May; 20(5): 437-40, 442, 444 Passim; Quiz 448. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10650359&dopt=Abstract
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Locally delivered doxycycline hyclate: case selection, preparation, and application. Author(s): Bogle G. Source: Compend Contin Educ Dent. 1999; 20(4 Suppl): 26-33; Quiz 35. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11908361&dopt=Abstract
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Long-term doxycycline-controlled expression of human tyrosine hydroxylase after direct adenovirus-mediated gene transfer to a rat model of Parkinson's disease. Author(s): Corti O, Sanchez-Capelo A, Colin P, Hanoun N, Hamon M, Mallet J. Source: Proceedings of the National Academy of Sciences of the United States of America. 1999 October 12; 96(21): 12120-5. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10518586&dopt=Abstract
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Long-term sub-antimicrobial doxycycline (Periostat) as adjunctive management in adult periodontitis: effects on subgingival bacterial population dynamics. Author(s): Thomas JG, Metheny RJ, Karakiozis JM, Wetzel JM, Crout RJ. Source: Advances in Dental Research. 1998 November; 12(2): 32-9. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=9972119&dopt=Abstract
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Long-term treatment with subantimicrobial dose doxycycline exerts no antibacterial effect on the subgingival microflora associated with adult periodontitis. Author(s): Walker C, Thomas J, Nango S, Lennon J, Wetzel J, Powala C. Source: J Periodontol. 2000 September; 71(9): 1465-71. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11022777&dopt=Abstract
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Long-term use of subantimicrobial dose doxycycline does not lead to changes in antimicrobial susceptibility. Author(s): Thomas J, Walker C, Bradshaw M. Source: J Periodontol. 2000 September; 71(9): 1472-83. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11022778&dopt=Abstract
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Maintenance therapy of melioidosis with ciprofloxacin plus azithromycin compared with cotrimoxazole plus doxycycline. Author(s): Chetchotisakd P, Chaowagul W, Mootsikapun P, Budhsarawong D, Thinkamrop B. Source: The American Journal of Tropical Medicine and Hygiene. 2001 JanuaryFebruary; 64(1-2): 24-7. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11425157&dopt=Abstract
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Malignant pleural effusions treated with high dose intrapleural doxycycline: clinical efficacy and tolerance. Author(s): Prevost A, Nazeyrollas P, Milosevic D, Fernandez-Valoni A. Source: Oncol Rep. 1998 March-April; 5(2): 363-6. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=9468558&dopt=Abstract
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Matrix metalloproteinase-8 is expressed in rheumatoid synovial fibroblasts and endothelial cells. Regulation by tumor necrosis factor-alpha and doxycycline. Author(s): Hanemaaijer R, Sorsa T, Konttinen YT, Ding Y, Sutinen M, Visser H, van Hinsbergh VW, Helaakoski T, Kainulainen T, Ronka H, Tschesche H, Salo T. Source: The Journal of Biological Chemistry. 1997 December 12; 272(50): 31504-9. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=9395486&dopt=Abstract
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Measured versus self-reported compliance with doxycycline therapy for chlamydiaassociated syndromes: high therapeutic success rates despite poor compliance. Author(s): Bachmann LH, Stephens J, Richey CM, Hook EW 3rd. Source: Sexually Transmitted Diseases. 1999 May; 26(5): 272-8. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10333280&dopt=Abstract
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Mefloquine compared with doxycycline for the prophylaxis of malaria in Indonesian soldiers. A randomized, double-blind, placebo-controlled trial. Author(s): Ohrt C, Richie TL, Widjaja H, Shanks GD, Fitriadi J, Fryauff DJ, Handschin J, Tang D, Sandjaja B, Tjitra E, Hadiarso L, Watt G, Wignall FS. Source: Annals of Internal Medicine. 1997 June 15; 126(12): 963-72. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=9182474&dopt=Abstract
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Mefloquine versus doxycycline for malaria prophylaxis in intermittent exposure of Israeli Air Force aircrew in Rwanda. Author(s): Shamiss A, Atar E, Zohar L, Cain Y. Source: Aviation, Space, and Environmental Medicine. 1996 September; 67(9): 872-3. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=9025805&dopt=Abstract
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Minocycline versus doxycycline in the treatment of Lyme neuroborreliosis. Author(s): Cunha BA. Source: Clinical Infectious Diseases : an Official Publication of the Infectious Diseases Society of America. 2000 January; 30(1): 237-8. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10619782&dopt=Abstract
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Modulation of cell growth and transformation by doxycycline-regulated FGF-2 expression in NIH-3T3 cells. Author(s): Gualandris A, Arese M, Shen B, Rifkin DB. Source: Journal of Cellular Physiology. 1999 November; 181(2): 273-84. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10497306&dopt=Abstract
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Modulation of oxidative burst of neutrophils by doxycycline in patients with acute myocardial infarction. Author(s): Takeshita S, Ono Y, Kozuma K, Suzuki M, Kawamura Y, Yokoyama N, Furukawa T, Isshiki T. Source: The Journal of Antimicrobial Chemotherapy. 2002 February; 49(2): 411-3. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11815591&dopt=Abstract
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Multi-center comparative evaluation of subgingivally delivered sanguinarine and doxycycline in the treatment of periodontitis. I. Study design, procedures, and management. Author(s): Polson AM, Garrett S, Stoller NH, Bandt CL, Hanes PJ, Killoy WJ, Harrold CQ, Southard GL, Duke SP. Source: J Periodontol. 1997 February; 68(2): 110-8. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=9058327&dopt=Abstract
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Multi-center comparative evaluation of subgingivally delivered sanguinarine and doxycycline in the treatment of periodontitis. II. Clinical results. Author(s): Polson AM, Garrett S, Stoller NH, Bandt CL, Hanes PJ, Killoy WJ, Southard GL, Duke SP, Bogle GC, Drisko CH, Friesen LR. Source: J Periodontol. 1997 February; 68(2): 119-26. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=9058328&dopt=Abstract
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Neuropathologies in transgenic mice expressing human immunodeficiency virus type 1 Tat protein under the regulation of the astrocyte-specific glial fibrillary acidic protein promoter and doxycycline. Author(s): Kim BO, Liu Y, Ruan Y, Xu ZC, Schantz L, He JJ. Source: American Journal of Pathology. 2003 May; 162(5): 1693-707. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12707054&dopt=Abstract
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Neutrophil migration across the intestinal epithelial barrier--summary of in vitro data and description of a new transgenic mouse model with doxycycline-inducible interleukin-8 expression in intestinal epithelial cells. Author(s): Kucharzik T, Williams IR. Source: Pathobiology : Journal of Immunopathology, Molecular and Cellular Biology. 2002-2003; 70(3): 143-9. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12571418&dopt=Abstract
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Non-surgical periodontal therapy with adjunctive topical doxycycline: a double-blind randomized controlled multicenter study. Author(s): Eickholz P, Kim TS, Burklin T, Schacher B, Renggli HH, Schaecken MT, Holle R, Kubler A, Ratka-Kruger P. Source: Journal of Clinical Periodontology. 2002 February; 29(2): 108-17. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11895538&dopt=Abstract
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O'Brien's actinic granuloma in association with prolonged doxycycline phototoxicity. Author(s): Lim DS, Triscott J. Source: The Australasian Journal of Dermatology. 2003 February; 44(1): 67-70. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12581086&dopt=Abstract
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Ocular rosacea. Signs, symptoms, and tear studies before and after treatment with doxycycline. Author(s): Quarterman MJ, Johnson DW, Abele DC, Lesher JL Jr, Hull DS, Davis LS. Source: Archives of Dermatology. 1997 January; 133(1): 49-54. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=9006372&dopt=Abstract
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Oesophageal ulceration caused by doxycycline: an unusual complication. Author(s): Ullah R, Golchin K, Hampton S, Primrose WJ. Source: The Journal of Laryngology and Otology. 2000 June; 114(6): 467-8. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10962685&dopt=Abstract
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Oral administration of doxycycline reduces collagenase and gelatinase activities in extracts of human osteoarthritic cartilage. Author(s): Smith GN Jr, Yu LP Jr, Brandt KD, Capello WN. Source: The Journal of Rheumatology. 1998 March; 25(3): 532-5. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=9517776&dopt=Abstract
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Oral clindamycin and ciprofloxacin versus intramuscular ceftriaxone and oral doxycycline in the treatment of mild-to-moderate pelvic inflammatory disease in outpatients. Author(s): Arredondo JL, Diaz V, Gaitan H, Maradiegue E, Oyarzun E, Paz R, Reynal JL, Stamm W, Zambrano D. Source: Clinical Infectious Diseases : an Official Publication of the Infectious Diseases Society of America. 1997 February; 24(2): 170-8. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=9114143&dopt=Abstract
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Overexpression of p27(Kip1) by doxycycline-regulated adenoviral vectors inhibits endothelial cell proliferation and migration and impairs angiogenesis. Author(s): Goukassian D, Diez-Juan A, Asahara T, Schratzberger P, Silver M, Murayama T, Isner JM, Andres V. Source: The Faseb Journal : Official Publication of the Federation of American Societies for Experimental Biology. 2001 September; 15(11): 1877-85. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11532967&dopt=Abstract
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Past use of erythromycin, tetracycline, or doxycycline is not associated with risk of first myocardial infarction. Author(s): Jackson LA, Smith NL, Heckbert SR, Grayston JT, Siscovick DS, Psaty BM. Source: The Journal of Infectious Diseases. 2000 June; 181 Suppl 3: S563-5. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10839759&dopt=Abstract
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Periostat: low-dose doxycycline. A commentary. Author(s): Baer PN. Source: Periodontal Clin Investig. 1998 Fall; 20(2): 5. No Abstract Available. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=9863450&dopt=Abstract
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Pharmacodynamic interaction of doxycycline and artemisinin in Plasmodium falciparum. Author(s): Sponer U, Prajakwong S, Wiedermann G, Kollaritsch H, Wernsdorfer G, Wernsdorfer WH. Source: Antimicrobial Agents and Chemotherapy. 2002 January; 46(1): 262-4. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11751150&dopt=Abstract
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Pharmacodynamics of doxycycline. Author(s): Cunha BA, Domenico P, Cunha CB. Source: Clinical Microbiology and Infection : the Official Publication of the European Society of Clinical Microbiology and Infectious Diseases. 2000 May; 6(5): 270-3. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11168126&dopt=Abstract
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Pharmacokinetic profile of a locally administered doxycycline gel in crevicular fluid, blood, and saliva. Author(s): Kim TS, Burklin T, Schacher B, Ratka-Kruger P, Schaecken MT, Renggli HH, Fiehn W, Eickholz P. Source: J Periodontol. 2002 November; 73(11): 1285-91. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12479632&dopt=Abstract
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Photosensitivity due to doxycycline hydrochloride with an unusual flare. Author(s): Tanaka N, Kawada A, Ohnishi Y, Hiruma M, Tajima S, Akiyama M, Ishibashi A. Source: Contact Dermatitis. 1997 August; 37(2): 93-4. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=9285175&dopt=Abstract
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Phrenic nerve paralysis after doxycycline sclerotherapy for chylous fistula. Author(s): Kirse DJ, Suen JY, Stern SJ. Source: Otolaryngology and Head and Neck Surgery. 1997 June; 116(6 Pt 1): 680-3. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=9215384&dopt=Abstract
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Pilot clinical trial of intravenous doxycycline versus placebo for rheumatoid arthritis. Author(s): Pillemer S, Gulko P, Ligier S, Yarboro C, Gourley M, Goldbach-Mansky R, Siegel R, Hirsch R, Pucino F, Tilley B, Wilder RL. Source: The Journal of Rheumatology. 2003 January; 30(1): 41-3. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12508388&dopt=Abstract
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Potential application of low-dose doxycycline to treat periodontitis in postmenopausal women. Author(s): Payne JB, Reinhardt RA. Source: Advances in Dental Research. 1998 November; 12(2): 166-9. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=9972143&dopt=Abstract
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Potentiation of the antimalarial activity of atovaquone by doxycycline against Plasmodium falciparum in vitro. Author(s): Yeo AE, Edstein MD, Shanks GD, Rieckmann KH. Source: Parasitology Research. 1997; 83(5): 489-91. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=9197398&dopt=Abstract
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Preoperative treatment with doxycycline reduces aortic wall expression and activation of matrix metalloproteinases in patients with abdominal aortic aneurysms. Author(s): Curci JA, Mao D, Bohner DG, Allen BT, Rubin BG, Reilly JM, Sicard GA, Thompson RW. Source: Journal of Vascular Surgery : Official Publication, the Society for Vascular Surgery [and] International Society for Cardiovascular Surgery, North American Chapter. 2000 February; 31(2): 325-42. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10664501&dopt=Abstract
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Primaquine as prophylaxis for malaria for nonimmune travelers: A comparison with mefloquine and doxycycline. Author(s): Schwartz E, Regev-Yochay G. Source: Clinical Infectious Diseases : an Official Publication of the Infectious Diseases Society of America. 1999 December; 29(6): 1502-6. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10585803&dopt=Abstract
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Prolonged administration of doxycycline in patients with small asymptomatic abdominal aortic aneurysms: report of a prospective (Phase II) multicenter study. Author(s): Baxter BT, Pearce WH, Waltke EA, Littooy FN, Hallett JW Jr, Kent KC, Upchurch GR Jr, Chaikof EL, Mills JL, Fleckten B, Longo GM, Lee JK, Thompson RW. Source: Journal of Vascular Surgery : Official Publication, the Society for Vascular Surgery [and] International Society for Cardiovascular Surgery, North American Chapter. 2002 July; 36(1): 1-12. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12096249&dopt=Abstract
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Prophylaxis with single-dose doxycycline for the prevention of Lyme disease after an Ixodes scapularis tick bite. Author(s): Nadelman RB, Nowakowski J, Fish D, Falco RC, Freeman K, McKenna D, Welch P, Marcus R, Aguero-Rosenfeld ME, Dennis DT, Wormser GP; Tick Bite Study Group. Source: The New England Journal of Medicine. 2001 July 12; 345(2): 79-84. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11450675&dopt=Abstract
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Prospective comparison of the sclerosing agents doxycycline and bleomycin for the primary management of malignant pericardial effusion and cardiac tamponade. Author(s): Liu G, Crump M, Goss PE, Dancey J, Shepherd FA. Source: Journal of Clinical Oncology : Official Journal of the American Society of Clinical Oncology. 1996 December; 14(12): 3141-7. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=8955660&dopt=Abstract
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Prospective, randomized, double-blind trial investigating the effect of doxycycline on matrix metalloproteinase expression within atherosclerotic carotid plaques. Author(s): Axisa B, Loftus IM, Naylor AR, Goodall S, Jones L, Bell PR, Thompson MM. Source: Stroke; a Journal of Cerebral Circulation. 2002 December; 33(12): 2858-64. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12468782&dopt=Abstract
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Proteolytic cleavage of recombinant type 2A von Willebrand factor mutants R834W and R834Q: inhibition by doxycycline and by monoclonal antibody VP-1. Author(s): Tsai HM, Sussman II, Ginsburg D, Lankhof H, Sixma JJ, Nagel RL. Source: Blood. 1997 March 15; 89(6): 1954-62. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=9058716&dopt=Abstract
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Pulmonary nocardiosis after bone marrow transplantation successfully treated with doxycycline. Author(s): Kumar K, Jimenez V. Source: International Journal of Infectious Diseases : Ijid : Official Publication of the International Society for Infectious Diseases. 2001; 5(4): 222-4. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11953222&dopt=Abstract
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Radiographic osseous regeneration after initial therapy with systemic doxycycline. Author(s): Fowler EB, Breault LG, Wolfgang M. Source: Military Medicine. 2000 October; 165(10): 796-9. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11050879&dopt=Abstract
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Randomised controlled comparison of single-dose ciprofloxacin and doxycycline for cholera caused by Vibrio cholerae 01 or 0139. Author(s): Khan WA, Bennish ML, Seas C, Khan EH, Ronan A, Dhar U, Busch W, Salam MA. Source: Lancet. 1996 August 3; 348(9023): 296-300. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=8709688&dopt=Abstract
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Randomised, blinded, placebo controlled trial of doxycycline for chronic seronegative arthritis. Author(s): Smieja M, MacPherson DW, Kean W, Schmuck ML, Goldsmith CH, Buchanan W, Hart LE, Mahony JB. Source: Annals of the Rheumatic Diseases. 2001 December; 60(12): 1088-94. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11709448&dopt=Abstract
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Randomized controlled trial of doxycycline prophylaxis against leptospirosis in an endemic area. Author(s): Sehgal SC, Sugunan AP, Murhekar MV, Sharma S, Vijayachari P. Source: International Journal of Antimicrobial Agents. 2000 February; 13(4): 249-55. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10755239&dopt=Abstract
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Randomized open trial of gentamicin and doxycycline for eradication of Bartonella quintana from blood in patients with chronic bacteremia. Author(s): Foucault C, Raoult D, Brouqui P. Source: Antimicrobial Agents and Chemotherapy. 2003 July; 47(7): 2204-7. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12821469&dopt=Abstract
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Rapid high-performance liquid chromatographic method for determination of doxycycline in human plasma. Author(s): Zarghi A, Kebriaeezadeh A, Ahmadkhaniha R. Source: Boll Chim Farm. 2001 March-April; 140(2): 112-4. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11417385&dopt=Abstract
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Recrudescence of Plasmodium falciparum malaria contracted in Lombok, Indonesia after quinine/doxycycline and mefloquine: case report. Author(s): Tish KN, Pillans PI. Source: N Z Med J. 1997 July 11; 110(1047): 255-6. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=9251712&dopt=Abstract
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Regarding “Use of doxycycline to decrease the growth rate of abdominal aortic aneurysms: a randomized, double-blind, placebo-controlled pilot study”. Author(s): Baxter BT. Source: Journal of Vascular Surgery : Official Publication, the Society for Vascular Surgery [and] International Society for Cardiovascular Surgery, North American Chapter. 2001 October; 34(4): 757-8. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11668336&dopt=Abstract
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Regulation of cartilage collagenase by doxycycline. Author(s): Shlopov BV, Stuart JM, Gumanovskaya ML, Hasty KA. Source: The Journal of Rheumatology. 2001 April; 28(4): 835-42. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11327259&dopt=Abstract
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Reiter's syndrome as a manifestation of an immune reconstitution syndrome in an HIV-infected patient: successful treatment with doxycycline. Author(s): Neumann S, Kreth F, Schubert S, Mossner J, Caca K. Source: Clinical Infectious Diseases : an Official Publication of the Infectious Diseases Society of America. 2003 June 15; 36(12): 1628-9. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12802773&dopt=Abstract
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Removal of intracanal smear by doxycycline in vitro. Author(s): Barkhordar RA, Watanabe LG, Marshall GW, Hussain MZ. Source: Oral Surgery, Oral Medicine, Oral Pathology, Oral Radiology, and Endodontics. 1997 October; 84(4): 420-3. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=9347508&dopt=Abstract
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Residue study of doxycycline and 4-epidoxycycline in pigs medicated via-drinking water. Author(s): Croubels S, Baert K, De Busser J, De Backer P. Source: The Analyst. 1998 December; 123(12): 2733-6. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10435334&dopt=Abstract
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Response to doxycycline vs. mefloquine. Author(s): Conrad KA, Kiser WR. Source: Military Medicine. 1997 June; 162(6): Iii. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=9183154&dopt=Abstract
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Revisiting doxycycline. Author(s): Dooley DP. Source: Archives of Internal Medicine. 1998 July 13; 158(13): 1469-70. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=9665360&dopt=Abstract
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Safety and efficacy of sub-antimicrobial-dose doxycycline therapy in patients with adult periodontitis. Author(s): Ciancio S, Ashley R. Source: Advances in Dental Research. 1998 November; 12(2): 27-31. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=9972118&dopt=Abstract
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Sclerotherapy for malignant pleural effusions: a prospective randomized trial of bleomycin vs doxycycline with small-bore catheter drainage. Author(s): Patz EF Jr, McAdams HP, Erasmus JJ, Goodman PC, Culhane DK, Gilkeson RC, Herndon J. Source: Chest. 1998 May; 113(5): 1305-11. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=9596311&dopt=Abstract
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Sclerotherapy with use of doxycycline after percutaneous drainage of postoperative lymphoceles. Author(s): Caliendo MV, Lee DE, Queiroz R, Waldman DL. Source: Journal of Vascular and Interventional Radiology : Jvir. 2001 January; 12(1): 73-7. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11200357&dopt=Abstract
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Short report: severe hiccups secondary to doxycycline-induced esophagitis during treatment of malaria. Author(s): Tzianetas I, Habal F, Keystone JS. Source: The American Journal of Tropical Medicine and Hygiene. 1996 February; 54(2): 203-4. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=8619448&dopt=Abstract
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Significant complications of doxycycline. Author(s): Watts TL. Source: British Dental Journal. 2003 July 26; 195(2): 65. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12881731&dopt=Abstract
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Simple and reliable method of doxycycline determination in human plasma and biological tissues. Author(s): Axisa B, Naylor AR, Bell PR, Thompson MM. Source: J Chromatogr B Biomed Sci Appl. 2000 July 21; 744(2): 359-65. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10993525&dopt=Abstract
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Single dose oral azithromycin versus seven day doxycycline in the treatment of nongonococcal mucopurulent endocervicitis. Author(s): Sendag F, Terek C, Tuncay G, Ozkinay E, Guven M. Source: The Australian & New Zealand Journal of Obstetrics & Gynaecology. 2000 February; 40(1): 44-7. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10870778&dopt=Abstract
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Single-dose doxycycline for the prevention of Lyme disease. Author(s): Bellovin SM. Source: The New England Journal of Medicine. 2001 November 1; 345(18): 1349; Author Reply 1349-50. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11794162&dopt=Abstract
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Single-dose doxycycline for the prevention of Lyme disease. Author(s): Leenders AC. Source: The New England Journal of Medicine. 2001 November 1; 345(18): 1349; Author Reply 1349-50. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11794161&dopt=Abstract
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Single-dose doxycycline for the prevention of Lyme disease. Author(s): Pontrelli L, Dattwyler R, Nachman S. Source: The New England Journal of Medicine. 2001 November 1; 345(18): 1348; Author Reply 1349-50. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11794160&dopt=Abstract
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Single-dose doxycycline for the prevention of Lyme disease. Author(s): Levy PD, Kirrane BM, Hexdall AH. Source: The New England Journal of Medicine. 2001 November 1; 345(18): 1348-9; Author Reply 1349-50. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11794159&dopt=Abstract
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Specificity of inhibition of matrix metalloproteinase activity by doxycycline: relationship to structure of the enzyme. Author(s): Smith GN Jr, Mickler EA, Hasty KA, Brandt KD. Source: Arthritis and Rheumatism. 1999 June; 42(6): 1140-6. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10366106&dopt=Abstract
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Stringent control of gene expression in vivo by using novel doxycycline-dependent trans-activators. Author(s): Lamartina S, Roscilli G, Rinaudo CD, Sporeno E, Silvi L, Hillen W, Bujard H, Cortese R, Ciliberto G, Toniatti C. Source: Human Gene Therapy. 2002 January 20; 13(2): 199-210. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11812277&dopt=Abstract
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Subantimicrobial dose doxycycline as an adjunct to scaling and root planing: posttreatment effects. Author(s): Caton JG, Ciancio SG, Blieden TM, Bradshaw M, Crout RJ, Hefti AF, Massaro JM, Polson AM, Thomas J, Walker C. Source: Journal of Clinical Periodontology. 2001 August; 28(8): 782-9. English, French, German. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11442739&dopt=Abstract
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Successful double-blinded, randomized, placebo-controlled field trial of azithromycin and doxycycline as prophylaxis for malaria in western Kenya. Author(s): Andersen SL, Oloo AJ, Gordon DM, Ragama OB, Aleman GM, Berman JD, Tang DB, Dunne MW, Shanks GD. Source: Clinical Infectious Diseases : an Official Publication of the Infectious Diseases Society of America. 1998 January; 26(1): 146-50. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=9455524&dopt=Abstract
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Successful oral doxycycline treatment of Lyme disease-associated facial palsy and meningitis. Author(s): Dotevall L, Hagberg L. Source: Clinical Infectious Diseases : an Official Publication of the Infectious Diseases Society of America. 1999 March; 28(3): 569-74. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10194080&dopt=Abstract
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Successful treatment of acquired reactive perforating collagenosis with doxycycline. Author(s): Brinkmeier T, Schaller J, Herbst RA, Frosch PJ. Source: Acta Dermato-Venereologica. 2002; 82(5): 393-5. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12430750&dopt=Abstract
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Successful treatment with doxycycline and nicotinamide of two cases of persistent pemphigoid gestationis. Author(s): Amato L, Coronella G, Berti S, Gallerani I, Moretti S, Fabbri P. Source: The Journal of Dermatological Treatment. 2002 September; 13(3): 143-6. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12227878&dopt=Abstract
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Suppurative panniculitis associated with alpha 1-antitrypsin deficiency (PiSZ phenotype) treated with doxycycline. Author(s): Chng WJ, Henderson CA. Source: The British Journal of Dermatology. 2001 June; 144(6): 1282-3. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11422069&dopt=Abstract
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Susceptibility of Porphyromonas gingivalis in biofilms to amoxicillin, doxycycline and metronidazole. Author(s): Larsen T. Source: Oral Microbiology and Immunology. 2002 October; 17(5): 267-71. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12354206&dopt=Abstract
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Sustained response to doxycycline therapy in two patients with SAPHO syndrome. Author(s): Ballara SC, Siraj QH, Maini RN, Venables PJ. Source: Arthritis and Rheumatism. 1999 April; 42(4): 819-21. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10211901&dopt=Abstract
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Systemic doxycycline administration in the treatment of periodontal infections (I). Effect on the subgingival microbiota. Author(s): Feres M, Haffajee AD, Goncalves C, Allard KA, Som S, Smith C, Goodson JM, Socransky SS. Source: Journal of Clinical Periodontology. 1999 December; 26(12): 775-83. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10599904&dopt=Abstract
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Systemic doxycycline administration in the treatment of periodontal infections (II). Effect on antibiotic resistance of subgingival species. Author(s): Feres M, Haffajee AD, Goncalves C, Allard KA, Som S, Smith C, Goodson JM, Socransky SS. Source: Journal of Clinical Periodontology. 1999 December; 26(12): 784-92. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10599905&dopt=Abstract
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Teratogenic study of doxycycline. Author(s): Czeizel AE, Rockenbauer M. Source: Obstetrics and Gynecology. 1997 April; 89(4): 524-8. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=9083306&dopt=Abstract
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The “cyclic” regimen of low-dose doxycycline for adult periodontitis: a preliminary study. Author(s): Crout RJ, Lee HM, Schroeder K, Crout H, Ramamurthy NS, Wiener M, Golub LM. Source: J Periodontol. 1996 May; 67(5): 506-14. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=8724709&dopt=Abstract
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The A-X of Atridox. Author(s): Sinclair G. Source: Ann R Australas Coll Dent Surg. 2000 October; 15: 157-8. No Abstract Available. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11709928&dopt=Abstract
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The effect of doxycycline treatment on the development of protective immunity in a murine model of chlamydial genital infection. Author(s): Su H, Morrison R, Messer R, Whitmire W, Hughes S, Caldwell HD. Source: The Journal of Infectious Diseases. 1999 October; 180(4): 1252-8. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10479155&dopt=Abstract
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The effect of human lactoferrin on the MICs of doxycycline and rifampicin for Burkholderia cepacia and Pseudomonas aeruginosa strains. Author(s): Alkawash M, Head M, Alshami I, Soothill JS. Source: The Journal of Antimicrobial Chemotherapy. 1999 September; 44(3): 385-7. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10511407&dopt=Abstract
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The effect of irrigation with doxycycline or citric acid on leakage and osseous wound healing. Author(s): Davis JL, Jeansonne BG, Davenport WD, Gardiner D. Source: Journal of Endodontics. 2003 January; 29(1): 31-5. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12540216&dopt=Abstract
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The effect of locally delivered controlled-release doxycycline or scaling and root planing on periodontal maintenance patients over 9 months. Author(s): Garrett S, Adams DF, Bogle G, Donly K, Drisko CH, Hallmon WW, Hancock EB, Hanes P, Hawley CE, Johnson L, Kiger R, Killoy W, Mellonig JT, Raab FJ, Ryder M, Stoller N, Polson A, Wang HL, Wolinsky LE, Yukna RA, Harrold CQ, Hill M, Johnson VB, Soouthard GL. Source: J Periodontol. 2000 January; 71(1): 22-30. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10695935&dopt=Abstract
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The effect of prolonged doxycycline therapy on Chlamydia pneumoniae serological markers, coronary heart disease risk factors and forearm basal nitric oxide production. Author(s): Sinisalo J, Mattila K, Nieminen MS, Valtonen V, Syrjala M, Sundberg S, Saikku P. Source: The Journal of Antimicrobial Chemotherapy. 1998 January; 41(1): 85-92. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=9511041&dopt=Abstract
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The effects of intravenous doxycycline therapy for rheumatoid arthritis: a randomized, double-blind, placebo-controlled trial. Author(s): St Clair EW, Wilkinson WE, Pisetsky DS, Sexton DJ, Drew R, Kraus VB, Greenwald RA. Source: Arthritis and Rheumatism. 2001 May; 44(5): 1043-7. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11357896&dopt=Abstract
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The effects of subgingival calculus on the clinical outcomes of locally-delivered controlled-release doxycycline compared to scaling and root planing. Author(s): Johnson LR, Stoller NH, Polson A, Harrold CQ, Ryder M, Garrett S. Source: Journal of Clinical Periodontology. 2002 February; 29(2): 87-91. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11895536&dopt=Abstract
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The effects of sustained release doxycycline on the anaerobic flora and antibioticresistant patterns in subgingival plaque and saliva. Author(s): Walker CB, Godowski KC, Borden L, Lennon J, Nango S, Stone C, Garrett S. Source: J Periodontol. 2000 May; 71(5): 768-74. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10872958&dopt=Abstract
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The efficacy of doxycycline as a pleural sclerosing agent in malignant pleural effusion: a prospective study. Author(s): Pulsiripunya C, Youngchaiyud P, Pushpakom R, Maranetra N, Nana A, Charoenratanakul S. Source: Respirology (Carlton, Vic.). 1996 March; 1(1): 69-72. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=9432409&dopt=Abstract
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The end of antibiotic treatment in adults with acute sinusitis-like complaints in general practice? A placebo-controlled double-blind randomized doxycycline trial. Author(s): Stalman W, van Essen GA, van der Graaf Y, de Melker RA. Source: The British Journal of General Practice : the Journal of the Royal College of General Practitioners. 1997 December; 47(425): 794-9. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=9463979&dopt=Abstract
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The pharmacokinetic profile of a biodegradable controlled-release delivery system containing doxycycline compared to systemically delivered doxycycline in gingival crevicular fluid, saliva, and serum. Author(s): Stoller NH, Johnson LR, Trapnell S, Harrold CQ, Garrett S. Source: J Periodontol. 1998 October; 69(10): 1085-91. Erratum In: J Periodontol 1999 February; 70(2): 238. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=9802705&dopt=Abstract
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The potential role of doxycycline in the treatment of osteoarthritis of the temporomandibular joint. Author(s): Israel HA, Ramamurthy NS, Greenwald R, Golub L. Source: Advances in Dental Research. 1998 November; 12(2): 51-5. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=9972122&dopt=Abstract
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The significance of prior mechanical therapy for changes of periodontal status achieved by local delivery of a doxycyclinehyclate containing gel. Author(s): Wolinsky LE, Camargo PM, Polson A, Ryder M, Garrett S. Source: Journal of Clinical Periodontology. 2001 December; 28(12): 1115-20. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11737508&dopt=Abstract
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The use of locally delivered doxycycline in the treatment of periodontitis. Clinical results. Author(s): Drisko CH. Source: Journal of Clinical Periodontology. 1998 November; 25(11 Pt 2): 947-52; Discussion 978-9. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=9839851&dopt=Abstract
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Tolerability of doxycycline monohydrate salt vs. chloroquine-proguanil in malaria chemoprophylaxis. Author(s): Pages F, Boutin JP, Meynard JB, Keundjian A, Ryfer S, Giurato L, Baudon D. Source: Tropical Medicine & International Health : Tm & Ih. 2002 November; 7(11): 91924. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12390596&dopt=Abstract
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Treatment for community acquired pneumonia: more support for doxycycline. Author(s): Ditmanson L, Apgar D. Source: Archives of Internal Medicine. 1999 August 9-23; 159(15): 1814-5. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10448791&dopt=Abstract
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Treatment of endocarditis due to vancomycin-resistant Enterococcus faecium with quinupristin/dalfopristin, doxycycline, and rifampin: a synergistic drug combination. Author(s): Matsumura S, Simor AE. Source: Clinical Infectious Diseases : an Official Publication of the Infectious Diseases Society of America. 1998 December; 27(6): 1554-6. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=9868693&dopt=Abstract
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Treatment of human brucellosis with doxycycline and gentamicin. Author(s): Solera J, Espinosa A, Martinez-Alfaro E, Sanchez L, Geijo P, Navarro E, Escribano J, Fernandez JA. Source: Antimicrobial Agents and Chemotherapy. 1997 January; 41(1): 80-4. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=8980759&dopt=Abstract
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Treatment of human brucellosis with netilmicin and doxycycline. Author(s): Solera J, Espinosa A, Geijo P, Martinez-Alfaro E, Saez L, Sepulveda MA, Ruiz-Ribo MD. Source: Clinical Infectious Diseases : an Official Publication of the Infectious Diseases Society of America. 1996 March; 22(3): 441-5. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=8852960&dopt=Abstract
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Treatment of persisting bilioma using endoscopic retrograde cholangiography and doxycycline. Author(s): Rau HM, Truong S, Uhlig H, Schumpelick V. Source: Endoscopy. 2000 February; 32(2): S12. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10696849&dopt=Abstract
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Treatment of Q fever endocarditis: comparison of 2 regimens containing doxycycline and ofloxacin or hydroxychloroquine. Author(s): Raoult D, Houpikian P, Tissot Dupont H, Riss JM, Arditi-Djiane J, Brouqui P. Source: Archives of Internal Medicine. 1999 January 25; 159(2): 167-73. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=9927100&dopt=Abstract
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Treatment of recalcitrant recurrent corneal erosions with inhibitors of matrix metalloproteinase-9, doxycycline and corticosteroids. Author(s): Dursun D, Kim MC, Solomon A, Pflugfelder SC. Source: American Journal of Ophthalmology. 2001 July; 132(1): 8-13. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11438047&dopt=Abstract
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Treatment of rosacea with doxycycline monohydrate. Author(s): Bikowski JB. Source: Cutis; Cutaneous Medicine for the Practitioner. 2000 August; 66(2): 149-52. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10955198&dopt=Abstract
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Treatment of vancomycin-resistant Enterococcus faecium with RP 59500 (quinupristin-dalfopristin) administered by intermittent or continuous infusion, alone or in combination with doxycycline, in an in vitro pharmacodynamic infection model with simulated endocardial vegetations. Author(s): Aeschlimann JR, Zervos MJ, Rybak MJ. Source: Antimicrobial Agents and Chemotherapy. 1998 October; 42(10): 2710-7. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=9756782&dopt=Abstract
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Treatment with subantimicrobial dose doxycycline improves the efficacy of scaling and root planing in patients with adult periodontitis. Author(s): Caton JG, Ciancio SG, Blieden TM, Bradshaw M, Crout RJ, Hefti AF, Massaro JM, Polson AM, Thomas J, Walker C. Source: J Periodontol. 2000 April; 71(4): 521-32. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10807113&dopt=Abstract
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Two multi-center studies evaluating locally delivered doxycycline hyclate, placebo control, oral hygiene, and scaling and root planing in the treatment of periodontitis. Author(s): Garrett S, Johnson L, Drisko CH, Adams DF, Bandt C, Beiswanger B, Bogle G, Donly K, Hallmon WW, Hancock EB, Hanes P, Hawley CE, Kiger R, Killoy W, Mellonig JT, Polson A, Raab FJ, Ryder M, Stoller NH, Wang HL, Wolinsky LE, Evans GH, Harrold CQ, Arnold RM, Southard GL, et al. Source: J Periodontol. 1999 May; 70(5): 490-503. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10368053&dopt=Abstract
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Use of doxycycline for leptospirosis after high-risk exposure in Sao Paulo, Brazil. Author(s): Gonsalez CR, Casseb J, Monteiro FG, Paula-Neto JB, Fernandez RB, Silva MV, Camargo ED, Mairinque JM, Tavares LC. Source: Revista Do Instituto De Medicina Tropical De Sao Paulo. 1998 January-February; 40(1): 59-61. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=9713140&dopt=Abstract
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Use of doxycycline to decrease the growth rate of abdominal aortic aneurysms: a randomized, double-blind, placebo-controlled pilot study. Author(s): Mosorin M, Juvonen J, Biancari F, Satta J, Surcel HM, Leinonen M, Saikku P, Juvonen T. Source: Journal of Vascular Surgery : Official Publication, the Society for Vascular Surgery [and] International Society for Cardiovascular Surgery, North American Chapter. 2001 October; 34(4): 606-10. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11668312&dopt=Abstract
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Use of doxycycline-controlled gene expression to reversibly alter milk-protein composition in transgenic mice. Author(s): Soulier S, Stinnakre MG, Lepourry L, Mercier JC, Vilotte JL. Source: European Journal of Biochemistry / Febs. 1999 March; 260(2): 533-9. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10095792&dopt=Abstract
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Utilisation of locally delivered doxycycline in non-surgical treatment of chronic periodontitis. A comparative multi-centre trial of 2 treatment approaches. Author(s): Wennstrom JL, Newman HN, MacNeill SR, Killoy WJ, Griffiths GS, Gillam DG, Krok L, Needleman IG, Weiss G, Garrett S. Source: Journal of Clinical Periodontology. 2001 August; 28(8): 753-61. English, French, German. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11442735&dopt=Abstract
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von Willebrand factor proteolysis and doxycycline in thrombotic thrombocytopenic purpura. Author(s): Raife TJ, Aster RH. Source: Lancet. 1998 July 25; 352(9124): 324. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=9690440&dopt=Abstract
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CHAPTER 2. NUTRITION AND DOXYCYCLINE Overview In this chapter, we will show you how to find studies dedicated specifically to nutrition and doxycycline.
Finding Nutrition Studies on Doxycycline 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 “doxycycline” (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 “doxycycline” (or a synonym): •
Activity of artemether-azithromycin versus artemether-doxycycline in the treatment of multiple drug resistant falciparum malaria. Author(s): Clinical Pharmacology Unit, Faculty of Tropical Medicine, Mahidol University, Bangkok, Thailand. Source: Na Bangchang, K Kanda, T Tipawangso, P Thanavibul, A Suprakob, K Ibrahim, M Wattanagoon, Y Karbwang, J Southeast-Asian-J-Trop-Med-Public-Health. 1996 September; 27(3): 522-5 0038-3619
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Antibiotics for prophylaxis of Plasmodium falciparum infections: in vitro activity of doxycycline against Senegalese isolates. Author(s): Unite de Parasitologie, Institut de Medecine Tropicale du Service de Sante des Armees, Marseille, France. Source: Pradines, B Spiegel, A Rogier, C Tall, A Mosnier, J Fusai, T Trape, J F Parzy, D Am-J-Trop-Med-Hyg. 2000 January; 62(1): 82-5 0002-9637
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Comparison of the antibacterial effects on subgingival microflora of two different resorbable base materials containing doxycycline. Author(s): Department of Periodontology, Gazi University School of Dentistry, Ankara, Turkey. Source: Taner, I L Ozcan, G Doganay, T Iscanolu, M Taplamacioglu, B Gultekin, S E Balos, K J-Nihon-Univ-Sch-Dent. 1994 September; 36(3): 183-90 0029-0432
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Differential patterns of response to doxycycline and transforming growth factor beta1 in the down-regulation of collagenases in osteoarthritic and normal human chondrocytes. Author(s): Department of Veterans Affairs Medical Center, and University of Tennessee, Memphis 38104, USA. Source: Shlopov, B V Smith, G N Cole, A A Hasty, K A Arthritis-Rheum. 1999 April; 42(4): 719-27 0004-3591
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Doxycycline and tissue repair in rats. Author(s): Department of Internal Medicine, Division of Cardiology, PhilippsUniversity Marburg. Source: Lamparter, Steffen Slight, Simon H Weber, Karl T J-Lab-Clin-Med. 2002 May; 139(5): 295-302 0022-2143
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Doxycycline carrageenate--an improved formulation providing more reliable absorption and plasma concentrations at high gastric pH than doxycycline monohydrate. Author(s): Pharmaco Medical Consultants-PMC AB, Uppsala, Sweden. Source: Grahnen, A Olsson, B Johansson, G Eckernas, S A Eur-J-Clin-Pharmacol. 1994; 46(2): 143-6 0031-6970
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Doxycycline induces expression of P glycoprotein in MCF-7 breast carcinoma cells. Author(s): Department of Veterinary Physiology and Pharmacology, Texas A&M University College of Veterinary Medicine, College Station, Texas 77843-4466, USA. Source: Mealey, Katrina L Barhoumi, Rola Burghardt, Robert C Safe, Stephen Kochevar, Deborah T Antimicrob-Agents-Chemother. 2002 March; 46(3): 755-61 0066-4804
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Doxycycline plasma concentrations in macaws fed a medicate corn diet. Author(s): Department of Companion Animal and Special Species Medicine, College of Veterinary Medicine, North Carolina State University, Raleigh 27606.
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Source: Prus, S E Clubb, S L Flammer, K Avian-Dis. 1992 Apr-June; 36(2): 480-3 00052086 •
Effects of tiaprofenic acid on urinary pyridinium crosslinks in adjuvant arthritic rats: comparison with doxycycline. Author(s): Hoechst AG, Wieshaden, Germany.
[email protected] Source: Weithmann, K U Schlotte, V Jeske, V Seiffge, D Laber, A Haase, B Schleyerbach, R Inflamm-Res. 1997 July; 46(7): 246-52 1023-3830
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Enhanced anticoagulant effect of coumarin derivatives induced by doxycycline coadministration. Author(s): Division of Medicine, Hadassah University Hospital, Jerusalem, Israel. Source: Caraco, Y Rubinow, A Ann-Pharmacother. 1992 September; 26(9): 1084-6 10600280
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High-dose methotrexate-doxycycline interaction. Author(s): Pharmacy Service, Dr. Peset University Hospital, Valencia, Spain.
[email protected] Source: Tortajada Ituren, J J Ordovas Baines, J P Llopis Salvia, P Jimenez Torres, N V Ann-Pharmacother. 1999 Jul-August; 33(7-8): 804-8 1060-0280
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Long-term doxycycline-controlled expression of human tyrosine hydroxylase after direct adenovirus-mediated gene transfer to a rat model of Parkinson's disease. Author(s): Laboratoire de Genetique Moleculaire de la Neurotransmission et des Processus Neurodegeneratifs, Centre National de la Recherche Scientifique, UMR9923, Paris, France. Source: Corti, O Sanchez Capelo, A Colin, P Hanoun, N Hamon, M Mallet, J Proc-NatlAcad-Sci-U-S-A. 1999 October 12; 96(21): 12120-5 0027-8424
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Pharmacodynamic interaction of doxycycline and artemisinin in Plasmodium falciparum. Author(s): Department of Specific Prophylaxis and Tropical Medicine, Institute of Pathophysiology, University of Vienna, A-1095 Vienna, Austria. Source: Sponer, Ulrike Prajakwong, Somsak Wiedermann, Gerhard Kollaritsch, Herwig Wernsdorfer, Gunther Wernsdorfer, Walther H Antimicrob-Agents-Chemother. 2002 January; 46(1): 262-4 0066-4804
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Pharmacokinetics of quinine and doxycycline in patients with acute falciparum malaria: a study in Africa. Author(s): CEMAF s.a., Poitiers, France. Source: Couet, W Laroche, R Floch, J J Istin, B Fourtillan, J B Sauniere, J F Ther-DrugMonit. 1991 November; 13(6): 496-501 0163-4356
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Potentiation of the antimalarial activity of atovaquone by doxycycline against Plasmodium falciparum in vitro. Author(s): Army Malaria Research Unit, Liverpool Military Area, NSW, Australia. Source: Yeo, A E Edstein, M D Shanks, G D Rieckmann, K H Parasitol-Res. 1997; 83(5): 489-91 0932-0113
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Prophylactic treatment of vivax and falciparum malaria with low-dose doxycycline. Author(s): Armed Forces Research Institute of Medical Sciences, Bangkok, Thailand. Source: Pang, L Limsomwong, N Singharaj, P J-Infect-Dis. 1988 November; 158(5): 11247 0022-1899
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Quinine toxicity when given with doxycycline and mefloquine. Author(s): Clinical Pharmacology Unit, Faculty of Tropical Medicine, Mahidol University, Bangkok, Thailand.
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Source: Karbwang, J Bangchang, K N Thanavibul, A Wattanakoon, Y Harinasuta, T Southeast-Asian-J-Trop-Med-Public-Health. 1994 June; 25(2): 397-400 0038-3619 •
Randomized controlled trial of doxycycline prophylaxis against leptospirosis in an endemic area. Author(s): Regional Medical Research Centre (Indian Council of Medical Research), Port Blair, Andaman and Nicobar Islands. Source: Sehgal, S C Sugunan, A P Murhekar, M V Sharma, S Vijayachari, P Int-JAntimicrob-Agents. 2000 February; 13(4): 249-55 0924-8579
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Recrudescence of Plasmodium falciparum malaria contracted in Lombok, Indonesia after quinine/doxycycline and mefloquine: case report. Author(s): Department of Medicine, Dunedin Hospital. Source: Tish, K N Pillans, P I N-Z-Med-J. 1997 July 11; 110(1047): 255-6 0028-8446
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Successful treatment with doxycycline and nicotinamide of two cases of persistent pemphigoid gestationis. Author(s): Department of Dermatological Sciences, University of Florence, Italy. Source: Amato, L Coronella, G Berti, S Gallerani, I Moretti, S Fabbri, P J-DermatologTreat. 2002 September; 13(3): 143-6 0954-6634
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The effect of human lactoferrin on the MICs of doxycycline and rifampicin for Burkholderia cepacia and Pseudomonas aeruginosa strains. Author(s): Department of Pathological Sciences, University of Manchester, Manchester Royal Infirmary, UK. Source: Alkawash, M Head, M Alshami, I Soothill, J S J-Antimicrob-Chemother. 1999 September; 44(3): 385-7 0305-7453
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Use of doxycycline-controlled gene expression to reversibly alter milk-protein composition in transgenic mice. Author(s): Laboratoire de Genetique Biochimique et de Cytogenetique, Institut National de la Recherche Agronomique, Jouy-en-Josas, France. Source: Soulier, S Stinnakre, M G Lepourry, L Mercier, J C Vilotte, J L Eur-J-Biochem. 1999 March; 260(2): 533-9 0014-2956
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Use of membranes containing 20% chlorhexidine and 40% doxycycline for treatment of chronic periodontal pockets. Author(s): Department of Periodontology, Gazi University School of Dentistry, Ankara, Turkey. Source: Ozcan, G Taner, I L Doganay, T Iscanoglu, M Taplamacioglu, B Gultekin, S E Balos, K J-Nihon-Univ-Sch-Dent. 1994 September; 36(3): 191-8 0029-0432
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 doxycycline; please note that any particular subject below may indicate either a therapeutic use, or a contraindication (potential danger), and does not reflect an official recommendation: •
Vitamins Vitamin K Source: Healthnotes, Inc.; www.healthnotes.com
•
Minerals Calcium Source: Healthnotes, Inc.; www.healthnotes.com
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Calcium Source: WholeHealthMD.com, LLC.; www.wholehealthmd.com Hyperlink: http://www.wholehealthmd.com/refshelf/substances_view/0,1525,884,00.html Iron Source: Healthnotes, Inc.; www.healthnotes.com Magnesium Source: Healthnotes, Inc.; www.healthnotes.com Magnesium Source: Integrative Medicine Communications; www.drkoop.com Zinc Source: Healthnotes, Inc.; www.healthnotes.com Zinc Source: WholeHealthMD.com, LLC.; www.wholehealthmd.com Hyperlink: http://www.wholehealthmd.com/refshelf/substances_view/0,1525,10071,00.html
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CHAPTER 3. ALTERNATIVE MEDICINE AND DOXYCYCLINE Overview In this chapter, we will begin by introducing you to official information sources on complementary and alternative medicine (CAM) relating to doxycycline. 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 doxycycline 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 “doxycycline” (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 doxycycline: •
A case of bullous reticulosis. Author(s): van Velde JL. Source: Dermatologica. 1974; 148(6): 377-81. No Abstract Available. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=4424121&dopt=Abstract
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A case of relapsing psittacosis associated with a stroke. Author(s): Vassallo M, Shepherd RJ. Source: Int J Clin Pract. 1997 June; 51(4): 261. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=9287275&dopt=Abstract
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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.
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Source: Journal of Chromatographic Science. 1978 March 10; 16(3): 93-101. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=641134&dopt=Abstract •
A new solution for the removal of the smear layer. Author(s): Torabinejad M, Khademi AA, Babagoli J, Cho Y, Johnson WB, Bozhilov K, Kim J, Shabahang S. Source: Journal of Endodontics. 2003 March; 29(3): 170-5. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12669874&dopt=Abstract
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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. Source: Febs Letters. 2002 April 24; 517(1-3): 115-20. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12062420&dopt=Abstract
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A retrospective study regarding the treatment of lupoid onychodystrophy in 30 dogs and literature review. Author(s): Mueller RS, Rosychuk RA, Jonas LD. Source: Journal of the American Animal Hospital Association. 2003 March-April; 39(2): 139-50. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12617542&dopt=Abstract
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Activation of recombinant human neutrophil procollagenase in the presence of doxycycline results in fragmentation of the enzyme and loss of enzyme activity. Author(s): Smith GN Jr, Brandt KD, Hasty KA. Source: Arthritis and Rheumatism. 1996 February; 39(2): 235-44. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=8849373&dopt=Abstract
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Acute deterioration of Charcot-Marie-Tooth disease IA (CMT IA) following 2 mg of vincristine chemotherapy. Author(s): Hildebrandt G, Holler E, Woenkhaus M, Quarch G, Reichle A, Schalke B, Andreesen R. Source: Annals of Oncology : Official Journal of the European Society for Medical Oncology / Esmo. 2000 June; 11(6): 743-7. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10942065&dopt=Abstract
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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:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11966868&dopt=Abstract
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Analysis of doxycycline by capillary electrophoresis. Method development and validation. Author(s): Gil EC, Van Schepdael A, Roets E, Hoogmartens J. Source: J Chromatogr A. 2000 October 20; 895(1-2): 43-9. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11105847&dopt=Abstract
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Analyzing the mechanisms of interferon-induced apoptosis using CrmA and hepatitis C virus NS5A. Author(s): Ezelle HJ, Balachandran S, Sicheri F, Polyak SJ, Barber GN. Source: Virology. 2001 March 1; 281(1): 124-37. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11222103&dopt=Abstract
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Antibiotic susceptibility testing of subgingival plaque samples. Author(s): Walker CB, Gordon JM, Socransky SS. Source: Journal of Clinical Periodontology. 1983 July; 10(4): 422-32. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=6577034&dopt=Abstract
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Autoimmune hepatitis triggered by Brucella infection or doxycycline or both. Author(s): Selimoglu MA, Ertekin V. Source: Int J Clin Pract. 2003 September; 57(7): 639-41. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=14529072&dopt=Abstract
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Bartholinitis after vulvovaginal surgery. Author(s): Peters WA 3rd. Source: American Journal of Obstetrics and Gynecology. 1998 June; 178(6): 1143-4. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=9662293&dopt=Abstract
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Bartonella henselae: etiology of pulmonary nodules in a patient with depressed cellmediated immunity. Author(s): Caniza MA, Granger DL, Wilson KH, Washington MK, Kordick DL, Frush DP, Blitchington RB. Source: Clinical Infectious Diseases : an Official Publication of the Infectious Diseases Society of America. 1995 June; 20(6): 1505-11. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=7548500&dopt=Abstract
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BCL6 overexpression prevents increase in reactive oxygen species and inhibits apoptosis induced by chemotherapeutic reagents in B-cell lymphoma cells. Author(s): Kurosu T, Fukuda T, Miki T, Miura O. Source: Oncogene. 2003 July 17; 22(29): 4459-68. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12881702&dopt=Abstract
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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:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=3641&dopt=Abstract
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Cell-based delivery of cytokines allows for the differentiation of a doxycycline inducible oligodendrocyte precursor cell line in vitro. Author(s): Muth H, Elmshauser C, Broad S, Schipke C, Kettenmann H, Beck E, Kann M, Motta I, Chen U. Source: The Journal of Gene Medicine. 2001 November-December; 3(6): 585-98. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11778905&dopt=Abstract
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Characterisation of isolates of Haemophilus paragallinarum from Indonesia. Author(s): Poernomo S, Sutarma, Rafiee M, Blackall PJ. Source: Aust Vet J. 2000 November; 78(11): 759-62. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11194721&dopt=Abstract
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Determination of flumequine and doxycycline in milk by a simple thin-layer chromatographic method. Author(s): Choma I, Grenda D, Malinowska I, Suprynowicz Z. Source: J Chromatogr B Biomed Sci Appl. 1999 October 29; 734(1): 7-14. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10574184&dopt=Abstract
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Doxycycline and tissue repair in rats. Author(s): Lamparter S, Slight SH, Weber KT. Source: The Journal of Laboratory and Clinical Medicine. 2002 May; 139(5): 295-302. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12032490&dopt=Abstract
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Effects of tiaprofenic acid on urinary pyridinium crosslinks in adjuvant arthritic rats: comparison with doxycycline. Author(s): Weithmann KU, Schlotte V, Jeske V, Seiffge D, Laber A, Haase B, Schleyerbach R. Source: Inflammation Research : Official Journal of the European Histamine Research Society. [et Al.]. 1997 July; 46(7): 246-52. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=9266272&dopt=Abstract
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Efficacy of enrofloxacin or doxycycline for treatment of Bartonella henselae or Bartonella clarridgeiae infection in cats. Author(s): Kordick DL, Papich MG, Breitschwerdt EB. Source: Antimicrobial Agents and Chemotherapy. 1997 November; 41(11): 2448-55. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=9371348&dopt=Abstract
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Elevation of urinary pyridinoline in adjuvant arthritic rats and its inhibition by doxycycline. Author(s): Ganu V, Doughty J, Spirito S, Goldberg R. Source: Annals of the New York Academy of Sciences. 1994 September 6; 732: 416-8. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=7978824&dopt=Abstract
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High-dose methotrexate-doxycycline interaction. Author(s): Tortajada-Ituren JJ, Ordovas-Baines JP, Llopis-Salvia P, Jimenez-Torres NV. Source: The Annals of Pharmacotherapy. 1999 July-August; 33(7-8): 804-8. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10466909&dopt=Abstract
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Histomorphometric evaluation of the effect of doxycycline on the healing of bone defects in experimental diabetes mellitus: a pilot study. Author(s): Alkan A, Erdem E, Gunhan O, Karasu C. Source: Journal of Oral and Maxillofacial Surgery : Official Journal of the American Association of Oral and Maxillofacial Surgeons. 2002 August; 60(8): 898-904. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12149735&dopt=Abstract
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Isolation of doxycycline, 6-epidoxycycline and 2-acetyl-2- decarboxamidometacycline from commercial metacycline by preparative column liquid chromatography on silica gel. Author(s): Naidong W, Verresen K, Busson R, Roets E, Hoogmartens J. Source: Journal of Chromatography. 1991 November 8; 586(1): 67-72. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=1666895&dopt=Abstract
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Occurrence of doxycycline resistant bacteria in the oral cavity after local administration of doxycycline in patients with periodontal disease. Author(s): Larsen T. Source: Scandinavian Journal of Infectious Diseases. 1991; 23(1): 89-95. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=2028232&dopt=Abstract
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Polarographic determination of some pharmaceutical products: bromphenindione, trihydroxyethylrutoside, glibenclamide, coenzyme a, doxycycline. Author(s): Silvestri S. Source: Pharmaceutica Acta Helvetiae. 1972 March-April; 47(3): 209-21. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=4624247&dopt=Abstract
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Removal of intracanal smear by doxycycline in vitro. Author(s): Barkhordar RA, Watanabe LG, Marshall GW, Hussain MZ. Source: Oral Surgery, Oral Medicine, Oral Pathology, Oral Radiology, and Endodontics. 1997 October; 84(4): 420-3. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=9347508&dopt=Abstract
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Systemic doxycycline administration in the treatment of periodontal infections (II). Effect on antibiotic resistance of subgingival species. Author(s): Feres M, Haffajee AD, Goncalves C, Allard KA, Som S, Smith C, Goodson JM, Socransky SS. Source: Journal of Clinical Periodontology. 1999 December; 26(12): 784-92. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10599905&dopt=Abstract
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The influence of divalent cations and doxycycline on iodoacetamide-inhibitable leukocyte adherence. Author(s): Gabler WL, Tsukuda N. Source: Res Commun Chem Pathol Pharmacol. 1991 November; 74(2): 131-40. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=1811277&dopt=Abstract
Additional Web Resources A number of additional Web sites offer encyclopedic information covering CAM and related topics. The following is a representative sample: •
Alternative Medicine Foundation, Inc.: http://www.herbmed.org/
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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/
The following is a specific Web list relating to doxycycline; 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 Food Poisoning Source: Integrative Medicine Communications; www.drkoop.com
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Lyme Disease Source: Integrative Medicine Communications; www.drkoop.com •
Herbs and Supplements Antibiotics Source: Healthnotes, Inc.; www.healthnotes.com Brewer's Yeast Source: Healthnotes, Inc.; www.healthnotes.com Doxycycline Source: Healthnotes, Inc.; www.healthnotes.com Probiotics Source: Healthnotes, Inc.; www.healthnotes.com Sanguinaria Alternative names: Bloodroot; Sanguinaria canadensis L. Source: Alternative Medicine Foundation, Inc.; www.amfoundation.org Tetracycline Derivatives Source: Integrative Medicine Communications; www.drkoop.com Tetracyclines Source: Healthnotes, Inc.; www.healthnotes.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. CLINICAL TRIALS AND DOXYCYCLINE Overview In this chapter, we will show you how to keep informed of the latest clinical trials concerning doxycycline.
Recent Trials on Doxycycline The following is a list of recent trials dedicated to doxycycline.8 Further information on a trial is available at the Web site indicated. •
Effects of low-dose doxycycline on oral bone loss Condition(s): Periodontitis; Osteopenia Study Status: This study is currently recruiting patients. Sponsor(s): National Institute of Dental and Craniofacial Research (NIDCR) Purpose - Excerpt: The primary purpose of this clinical trial is to determine whether low-dose doxycycline can reduce alveolar bone density loss in postmenopausal women not on hormone replacement therapy (i.e., estrogen-deficient). Phase(s): Phase III Study Type: Interventional Contact(s): see Web site below Web Site: http://clinicaltrials.gov/ct/show/NCT00066027
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A Randomized, Double-Blind, Placebo-Controlled, Multicenter Trial of the Safety and Efficacy of Ceftriaxone and Doxycycline in the Treatment of Patients with Seronegative Chronic Lyme Disease Condition(s): Lyme Disease Study Status: This study is no longer recruiting patients. Sponsor(s): National Institute of Allergy and Infectious Diseases (NIAID)
8
These are listed at www.ClinicalTrials.gov.
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Purpose - Excerpt: Lyme disease is the most common tick-borne disease in the United States. It is caused by the spirochete Borrelia burgdorferi. It may exist in an acute and chronic form. The purpose of this study is to determine the safety and effectiveness, in seronegative patients, of intensive antibiotic treatment in eliminating symptoms of Chronic Lyme Disease (CLD). Lyme disease is the most common tick-borne disease in the United States. It is caused by the spirochete Borrelia burgdorferi. It may exist in a chronic form and be the result of: 1) persistent infection by B. burgdorferi; 2) damage caused by the original infectious process; or 3) the presence of co-infection with another organism transmitted by Ixodes ticks. Phase(s): Phase III Study Type: Observational Contact(s): see Web site below Web Site: http://clinicaltrials.gov/ct/show/NCT00000938 •
Doxycycline and OA Progression Condition(s): Osteoarthritis Study Status: This study is no longer recruiting patients. Sponsor(s): National Institute of Arthritis and Musculoskeletal and Skin Diseases (NIAMS); National Institute on Aging (NIA) Purpose - Excerpt: This study will determine whether doxycycline decreases the severity or rate of progression of osteoarthritis (OA) in the knee. Nonsteroidal anti-inflammatory drugs (NSAIDs) are the most popular agents used to treat OA, but elderly women, in whom OA is especially common, are at greatest risk of developing serious side effects from NSAIDs. Our study targets overweight middle-aged women who have OA in one knee. Half of the 432 study participants will receive the treatment (doxycycline) and half will receive a placebo (inactive pill). Treatment with doxycycline (or placebo) will last 30 months, and participants and researchers will not know who is receiving doxycycline and who is receiving placebo until the end of the study. We will look for narrowing of the joint space in the knee that was not affected by OA at the start of the study. Joint space narrowing is a sign of OA. We will also use questionnaires to evaluate participants' symptoms and functioning. Phase(s): Phase III Study Type: Interventional Contact(s): see Web site below Web Site: http://clinicaltrials.gov/ct/show/NCT00000403
•
A Randomized, Double-Blind, Placebo-Controlled, Multicenter Trial of the Safety and Efficacy of Ceftriaxone and Doxycycline in the Treatment of Patients with Seropositive Chronic Lyme Disease Condition(s): Lyme Disease Study Status: This study is completed. Sponsor(s): National Institute of Allergy and Infectious Diseases (NIAID) Purpose - Excerpt: Lyme disease is the most common tick-borne disease in the United States. It is caused by the spirochete Borrelia burgdorferi. It may exist in a chronic form and be the result of: 1) active infection by B. burgdorferi; 2) damage caused by the
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original infectious process; or 3) the presence of co-infection with another organism transmitted by Ixodes ticks. The purpose of this study is to determine the safety and effectiveness, for seropositive patients, of intensive antibiotic treatment in eliminating symptoms of Chronic Lyme Disease (CLD). Phase(s): Phase III Study Type: Observational Contact(s): see Web site below Web Site: http://clinicaltrials.gov/ct/show/NCT00001101
Keeping Current on Clinical Trials The U.S. National Institutes of Health, through the National Library of Medicine, has developed ClinicalTrials.gov to provide current information about clinical research across the broadest number of diseases and conditions. The site was launched in February 2000 and currently contains approximately 5,700 clinical studies in over 59,000 locations worldwide, with most studies being conducted in the United States. ClinicalTrials.gov receives about 2 million hits per month and hosts approximately 5,400 visitors daily. To access this database, simply go to the Web site at http://www.clinicaltrials.gov/ and search by “doxycycline” (or synonyms). While ClinicalTrials.gov is the most comprehensive listing of NIH-supported clinical trials available, not all trials are in the database. The database is updated regularly, so clinical trials are continually being added. The following is a list of specialty databases affiliated with the National Institutes of Health that offer additional information on trials: •
For clinical studies at the Warren Grant Magnuson Clinical Center located in Bethesda, Maryland, visit their Web site: http://clinicalstudies.info.nih.gov/
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For clinical studies conducted at the Bayview Campus in Baltimore, Maryland, visit their Web site: http://www.jhbmc.jhu.edu/studies/index.html
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For cancer trials, visit the National Cancer Institute: http://cancertrials.nci.nih.gov/
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For eye-related trials, visit and search the Web page of the National Eye Institute: http://www.nei.nih.gov/neitrials/index.htm
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For heart, lung and blood trials, visit the Web page of the National Heart, Lung and Blood Institute: http://www.nhlbi.nih.gov/studies/index.htm
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For trials on aging, visit and search the Web site of the National Institute on Aging: http://www.grc.nia.nih.gov/studies/index.htm
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For rare diseases, visit and search the Web site sponsored by the Office of Rare Diseases: http://ord.aspensys.com/asp/resources/rsch_trials.asp
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For alcoholism, visit the National Institute on Alcohol Abuse and Alcoholism: http://www.niaaa.nih.gov/intramural/Web_dicbr_hp/particip.htm
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For trials on infectious, immune, and allergic diseases, visit the site of the National Institute of Allergy and Infectious Diseases: http://www.niaid.nih.gov/clintrials/
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For trials on arthritis, musculoskeletal and skin diseases, visit newly revised site of the National Institute of Arthritis and Musculoskeletal and Skin Diseases of the National Institutes of Health: http://www.niams.nih.gov/hi/studies/index.htm
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For hearing-related trials, visit the National Institute on Deafness and Other Communication Disorders: http://www.nidcd.nih.gov/health/clinical/index.htm
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For trials on diseases of the digestive system and kidneys, and diabetes, visit the National Institute of Diabetes and Digestive and Kidney Diseases: http://www.niddk.nih.gov/patient/patient.htm
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For drug abuse trials, visit and search the Web site sponsored by the National Institute on Drug Abuse: http://www.nida.nih.gov/CTN/Index.htm
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For trials on mental disorders, visit and search the Web site of the National Institute of Mental Health: http://www.nimh.nih.gov/studies/index.cfm
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For trials on neurological disorders and stroke, visit and search the Web site sponsored by the National Institute of Neurological Disorders and Stroke of the NIH: http://www.ninds.nih.gov/funding/funding_opportunities.htm#Clinical_Trials
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CHAPTER 5. PATENTS ON DOXYCYCLINE Overview Patents can be physical innovations (e.g. chemicals, pharmaceuticals, medical equipment) or processes (e.g. treatments or diagnostic procedures). The United States Patent and Trademark Office defines a patent as a grant of a property right to the inventor, issued by the Patent and Trademark Office.9 Patents, therefore, are intellectual property. For the United States, the term of a new patent is 20 years from the date when the patent application was filed. If the inventor wishes to receive economic benefits, it is likely that the invention will become commercially available within 20 years of the initial filing. It is important to understand, therefore, that an inventor’s patent does not indicate that a product or service is or will be commercially available. The patent implies only that the inventor has “the right to exclude others from making, using, offering for sale, or selling” the invention in the United States. While this relates to U.S. patents, similar rules govern foreign patents. In this chapter, we show you how to locate information on patents and their inventors. If you find a patent that is particularly interesting to you, contact the inventor or the assignee for further information. IMPORTANT NOTE: When following the search strategy described below, you may discover non-medical patents that use the generic term “doxycycline” (or a synonym) in their titles. To accurately reflect the results that you might find while conducting research on doxycycline, we have not necessarily excluded nonmedical patents in this bibliography.
Patents on Doxycycline By performing a patent search focusing on doxycycline, 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 9Adapted
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 doxycycline: •
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, 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
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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__ •
Application of catalysts containing rhodium Inventor(s): Heggie; William (Barreiro, PT), Hursthouse; Michael (Chelmsford, GB2), Page; Philip R. (Sintra, PT), Somerville; Richard (Hornchurch, GB2), Villax; Ivan (Lisboa Codex, PT) Assignee(s): Plurichemie Anstalt (Vaduz, LI) Patent Number: 4,863,639 Date filed: May 15, 1987 Abstract: The present invention refers to the compounds (.mu.-hydrazine-N.sup.1 :N.sup.2)-bis[bis(triphenylphosphine)-chlororhodium (I)] and di(.mu.-hydrazineN.sup.1 :N.sup.2)-bis[bis(triphenylphosphine)rhodium (I)] dichloride, which are homogenous hydrogenation catalysts and their application in the hydrogenation of the exocyclic methylene group of acid addition salts of 6-demethyl-6-deoxy-6-methylene-5hydroxytetracycline (methacycline) to prepare.alpha.-6-deoxy-5-hydroxytetracycline (doxycycline). Excerpt(s): The present invention refers to the compounds (.mu.-hydrazine-N.sup.1 :N.sup.2)-bis[bis(triphenylphosphine)-chlororhodium (I)] and di(.mu.-hydrazineN.sup.1 :N.sup.2)-bis[bis(triphenylphosphine)rhodium (I)]dichloride, which are homogenous hydrogenation catalysts and their application in the hydrogenation of the exocyclic methylene group of acid addition salts of 6-demethyl-6-deoxy-6-methylene-5hydroxytetracycline (methacycline) to prepare.alpha.-6-deoxy-5-hydroxytetracycline (doxycycline). Doxycycline is a wide-spectrum antibacterial agent, with widespread application in the treatment of numerous infections in humans and in animals. The hydrogenation of the exocyclic methylene group of methacycline can produce two epimers. The.alpha.-6-epimer is doxycycline, whilst the.beta.-6-epimer, called 6-epidoxycycline, is devoid of clincal utility. Thus, it is important that the hydrogenation does not co-produce this.beta.-6-epimer. In fact, the British Pharmacopoeia 1980 established a limit for the content of 6-epi-doxycycline in doxycycline of 2%. In the prior art, doxycycline was first described in 1960 in U.S. Pat. No. 3,200,149. Since that time many methods have been described for the preparation, in all of which the modification of the catalytic system has been described as producing improved yields or a purer product. In the field of heterogenous catalysis, U.S. Pat. Nos. 3,444,198, 3,849,491, 3,954,862 and 4,597,904 and the report in Chemical Abstracts 86, 89476 f (1977) of Hungarian Pat. No. 12,042 have all taught improved methods for the preparation of doxycycline and its analogues. Web site: http://www.delphion.com/details?pn=US04863639__
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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 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__
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Doxycycline aceturate Inventor(s): Fernandez; Piedad Amezua (Avenida del Poblado s/n - Edificio Montefresno escalera A, 1.degree. derech, Puerta Hierro, Madrid, ES) Assignee(s): none reported Patent Number: 3,932,490 Date filed: December 4, 1972 Abstract: Doxycycline aceturate is prepared by reacting doxycycline with aceturic acid in a solvent. The compound is useful for the same pharmacological purposes as doxycycline and is more soluble in water or aqueous solvents so that it is more suitable for parenteral administration. Excerpt(s): This invention relates to doxycycline aceturate and a process for preparing same. Doxycycline, the most modern broad-spectrum antibiotic of the tetracycline group, surpasses its other congener compounds in therapeutic efficiency because of its higher stability, better gastrointestinal absorbability and its slow urinary elimination. Thus, the concentration of it reaches higher and more stable haematic levels in less time after administration, thus permitting the use of a smaller dosage. The acute toxicity of this antibiotic is very low (the DL.sub.50 in mice being over 3984 mg. per kilo) and the chronic toxicity is low also. In extensive tests on mice carried out during periods of up to 180 days with doses thirty times higher than the average daily human therapeutic dose, no histological, anatomical, or physiological alterations were observed in comparison to the control specimens. Web site: http://www.delphion.com/details?pn=US03932490__
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Doxycycline compositions Inventor(s): Armstrong; William W. (Mill Neck, NY) Assignee(s): Pfizer Inc. (New York, NY) Patent Number: 4,086,332 Date filed: December 7, 1976 Abstract: Aqueous solutions of doxycycline or salts thereof, a pharmaceutically acceptable soluble magnesium compound and 2-pyrrolidone as a co-solvent, said solution having a pH of 3 to 7.5 and being useful as an injectable composition combining low viscosity, high potency, good clarity and good stability. Excerpt(s): This invention relates to antibiotic compositions suitable for pharmaceutical use. More particularly, it relates to aqueous doxycycline solutions containing 2pyrrolidone. Previous effects made to prepare high concentration doxycycline solutions have been unsuccessful. This is of particular importance in the case of veterinary parenteral compositions for administration to large animals. Japanese Patent Publication No. Sho 47-303 discloses stable aqueous solutions of p-biphenylmethyl (dl-tropyl.alpha.-tropinium) bromide, 2.5%, in which 2-pyrrolidone is present in a concentration of 20%. The use of polyvinylpyrrolidone at a concentration of 30% is also disclosed. The pH of these solutions is less than 7, the preferred range being 3-4. Web site: http://www.delphion.com/details?pn=US04086332__
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Doxycycline parenteral compositions Inventor(s): Noseworthy; Melvin M. (Gales Ferry, CT) Assignee(s): Pfizer Inc. (New York, NY) Patent Number: 3,957,980 Date filed: June 10, 1974 Abstract: Doxycycline compositions suitable for the preparation of injectable liquid preparations are disclosed. Excerpt(s): This invention relates to antibiotic compositions suitable for parenteral administration. More particularly it relates to novel doxycycline parenteral compositions. Because of the therapeutic importance of the tetracycline-type antibiotics, efforts have been made to prepare compositions suitable for parenteral administration. Aqueous solutions of doxycycline can be prepared in the highly acid or alkaline pH range, but these solutions are found objectionable due to their low stability and poor local tolerance upon injection. With the exception of polyvinylpyrrolidine compositions and Mannich base derivatives very little pharmaceutical technology has been developed for a parenteral form of doxycycline. It has now been found that stable injectable solutions of doxycycline can be provided by means of a novel aqueous pharmaceutical composition comprising a solution in water of from about 1% to 10% by weight of an antibiotic compound selected from doxycycline and the pharmaceutically acceptable acid addition salts thereof, together with about 3 to 8 molar proportions of a phosphate selected from phosphoric acid, sodium or potassium orthophosphate, metaphosphate, pyrophosphate, tripolyphosphate or hexametaphosphate, and about 3 to 8 molar proportions of a pharmaceutically acceptable magnesium salt soluble in said aqueous pharmaceutical composition, said composition having a pH value in the range of from about 1.0 to 3.5. Web site: http://www.delphion.com/details?pn=US03957980__
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Method to treat cancer with tetracyclines Inventor(s): Fife; Rose S. (5 Smith La., Zionsville, IN 46077), Sledge; George W. (612 King Dr., Indianapolis, IN 46260) Assignee(s): none reported Patent Number: 5,668,122 Date filed: May 1, 1995 Abstract: The present invention provides a method to treat susceptible cancers in humans comprising administering a cancer-treating amount of a member of the tetracycline family or a pharmaceutically acceptable salt thereof. Doxycycline, minocycline and tetracycline are utilized in the preferred method. Preferred methods of the present invention treat osteo-, breast, lung, prostate or Kaposi's cancers. Other aspects of the invention are described in the full application. Excerpt(s): Cancer is a leading cause of death in the United States. Breast, lung and prostate cancer alone cost billions of medical dollars each year. Most treatments now available are quite toxic to the human body; side effects such as nausea, vomiting, hair loss and fatigue cause hesitance and fear in cancer patients facing such treatments. The present invention provides a relatively non-toxic and simple treatment for cancers. This invention discloses a method to treat cancers by administering a member of the
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tetracycline family (TCN). The major cause of cancer morbidity and mortality in humans is metastatic disease. As a consequence, there has been much interest in the mechanisms involved in invasion of cells and metastasis. Several enzyme systems have been implicated in the metastatic process: metalloproteinases, cysteine proteases, and serine proteinases. Yagel, S.A. et al., 49 Cancer Research 3553 (1989), Dickson R. B., 41 J. Steroid Biochem. Molec. Biol. 389 (1992) and Zucker S. et al., 45 Cancer Research 6168 (1985). Inhibitors of metalloproteinases, especially of the collagenases, have been the focus of intense study. DeClerck A. et al., 52 Cancer Research 701 (1992). The present invention discloses that growth, migration and enzyme activity of human cancer cells can be altered by administration of TCNs. This invention provides a simple, non-toxic treatment for cancers. Web site: http://www.delphion.com/details?pn=US05668122__ •
Novel pharmaceutical composition Inventor(s): Bergwitz-Larsen; Carl-Aage (Vallingby, SE), sterlund; Rolf G. L. (Vallentuna, SE) Assignee(s): KabiVitrum AB (Stockholm, SE) Patent Number: 4,536,495 Date filed: March 4, 1983 Abstract: A novel complex of carrageenan and a member of the group consisting of emepronium, doxycycline, and propranolol, pharmaceutical preparations containing such a complex, and its use in medicine. Excerpt(s): The present invention relates to a novel complex of carrageenan and a member of the group consisting of emepronium, doxycycline and propranolol, and a process for the preparation thereof. The invention also relates to novel pharmaceutical compositions containing such a complex of carrageenan and active ingredient, a process for the preparation thereof and to the use of the complexes in medicine. The customary mode of administration of emepronium is by the oral route, mostly in the form of tablets which contain emepronium in the form of its bromide together with usual inert tabletting aids such as swelling agents. Patients taking emepronium bromide tablets are advised to swallow them with water. However, since patients suffering from bladder ailments at the same time often are advised to reduce their intake of fluid, there is a risk that the tablets are swallowed with too little water. The tablet may then, when disintegrating during its passage through the oesophagus, stick to the mucosa in the oesophagus whereby high local concentrations of emepronium bromide are created. Emepronium bromide has irritating effect on the mucosa, and such high local concentrations may cause severe irritation and ulceration in the oesophagus. Such effects have been described i.a. by Bennett, Oesophageal ulceration due to emepronium bromide, Lancet 1977, 1, 810. There is also risk for mouth ulcers caused by emepronium bromide. A further problem with emepronium bromide is that it tastes very bitter. Liquid dose formulations are therefore accepted by the patients only with difficulty. Web site: http://www.delphion.com/details?pn=US04536495__
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Process for the production of alpha-6-deoxytetracyclines Inventor(s): Bala; Kiran (New Delhi, IN), Grover; Inder P. S. (New Delhi, IN), Khanna; Jagmohan (New Delhi, IN) Assignee(s): Ranbaxy Laboratories Limited (IN) Patent Number: 4,973,719 Date filed: October 28, 1988 Abstract: A process for the hydrogenation of a 6-methylenetetracycline in the production of alpha-6-deoxytetracyclines, particularly the antibiotic doxycycline, in the presence of hydriodotetrakis (triphenylphosphine) rhodium (I) as a homogenous hydrogenation catalyst. The desired alpha-6-deoxy product is produced in high yields and stereospecificities, the process requiring the use of minimal quantities of rhodium metal in the hydrogenation catalyst per mole of the 6-methylenetetracycline hydrogenated. Excerpt(s): This invention relates to a process for the preparation of alpha-6deoxytetracyclines, and more particularly to such a process for the production of the antibiotic doxycycline, viz., alpha-6-deoxy-5-oxytetracycline. The preparation of doxycycline and other alpha-6-deoxytetracyclines was first described in Blackwood et al. U.S. Pat. No. 3,200,149 granted Aug. 10, 1965. That patent described their preparation by the catalytic hydrogenation of a corresponding 6-methylene intermediate, e.g., in the case of doxycycline, 11a-chloro-6-deoxy-6-demethyl-6-methylene-5-oxytetracycline (11achloro methacycline) or 6-deoxy-6-demethyl-6-methylene-5-oxytetracycline (methacycline), in the presence of a heterogeneous noble metal catalyst, e.g. palladium on carbon. The Blackwood patent disclosed the production, in yields of up to about 50%, of equimolar proportions of the diastereoisomers (epimers) of the 6-deoxytetracyclines. In the case of doxycycline, the patent disclosed the co-production of the corresponding beta epimer, beta-6-deoxy-5-oxytetracycline. Subsequent efforts have been directed to the development of syntheses for producing the 6-deoxytetracyclines in greater yields and with greater stereoselectivity of formation of the desired alpha epimers, e.g., doxycycline. Thus, Korst U.S. Pat. No. 3,444,198 granted May 13, 1969, disclosed that the stereoselectivity of formation of the alpha epimers may be increased when the noble metal hydrogenation catalyst is poisoned. The Korst patent described the formation of epimeric mixtures of the 6-deoxytetracyclines in total yields of up to about 60%, with the stereoselective production of the alpha epimers in amounts of up to about 90% of the epimeric product mixtures. The use of other noble metal or noble metal salt compositions as heterogeneous hydrogenation catalysts in the production of doxycycline has also been disclosed in the literature. See, for example, Morris U.S. Pat. No. 3,954,862 granted May 4, 1976 and Faubl et al U.S. Pat. No. 3,962,131 granted June 8, 1976. Web site: http://www.delphion.com/details?pn=US04973719__
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Recovery of doxycycline and products thereof Inventor(s): Villax; Ivan (1, Travessa do Ferreiro, Lisbon-3, PT) Assignee(s): none reported Patent Number: 4,061,676 Date filed: March 23, 1976
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Abstract: The present invention provides a process for the recovery of doxycycline and products thereof. Excerpt(s): Various processes have been described for the preparation of.alpha.-6deoxytetracyclines, also called 6-epi-6-deoxytetracyclines, of which the most important is the.alpha.-6-deoxy-5-hydroxytetracycline, commonly designated by the name of doxycycline, one of the most effective broad spectrum antibiotics. U.S. Pat. No. 3,200,149 obtains the.alpha.-6-deoxytetracyclines by catalytic hydrogenation of 6-deoxy-6demethyl-6-methylenetetracyclines or their 11a-chloro or fluoro derivatives. U.S. Pat. Nos. 3,165,531, and 3,484,483 prepare them from the 13-benzylthio-.alpha.-6deoxytetracyclines, the first one by reduction with Raney-nickel, and the second converts those same intermediates by reacting with a tri(lower alkyl) phosphite. Web site: http://www.delphion.com/details?pn=US04061676__ •
Synergistic antimicrobial compositions Inventor(s): David; Agoston (Budapest, HU), Kulcsar; Gabor (Budapest, HU), Sebestyen; Gyula (Budapest, HU), Zilahi; Tibor (Budapest, HU) Assignee(s): Chinoin Gyogyszer es Vegyeszeti Termekek Gyara Rt. (Budapest, HU) Patent Number: 4,501,732 Date filed: June 18, 1982 Abstract: This invention relates to new synergistic antimicrobial compositions containing primycin, doxycycline and sisomicin. Excerpt(s): The present invention relates to new synergistic antimicrobial compositions. The resistance of pathogens to commercially available active ingredients has increased to a great extent and thus several longused effective active ingredients cannot be effectively used any longer. In addition to the cromosomal resistance the recently discovered "plasmid resistance" is reponsible for the resistance phenomenon. The latter is capability to the pathogens of directly transfer the plasmid resistance thereof to individuals belonging to the same species or other species as well. Thus polyresistant pathogens may be produced within a short period. Web site: http://www.delphion.com/details?pn=US04501732__
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Tetracycline activity enhancement using doxycycline or sancycline Inventor(s): Levy; Stuart B. (Boston, MA) Assignee(s): Trustees of Tufts College (Boston, MA) Patent Number: 5,258,372 Date filed: March 20, 1991 Abstract: Methods and products for overcoming bacterial resistance to tetracycline-type antibiotics by inhibiting the plasmid-mediated active efflux system for tetracycline in the resistant bacterial cell by administering with tetracycline efflux system blocking agents of doxycycline or sancycline, thereby increasing the sensitivity of the resistant cell to tetracycline type antibiotics. Excerpt(s): This invention relates to methods and products for enhancing the effectiveness of antibiotics, more particularly, to methods and products for overcoming
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bacterial resistance to antibiotics of the tetracycline family. The tetracyclines are bacteriostatic antibiotics used to treat a broad spectrum of microbial disease agents in humans, animals and plants. Many bacteria are able to adapt to their environment in ways which permit them to become resistant to antibiotics. Strains of group A streptococci devoloped resistance to sulfadiazine during World War II. Resistant staphylococcal infections began to spread through public institutions and hospitals following the widespread use of penicillin. Since the introduction of tetracyclines into clinical practice, a number of microorganisms have developed resistance to these drugs. Treatment of bacterial infections in palm trees with tetracycline solutions through the root system has become increasingly ineffective. See Levy, "The Tetracyclines: Microbial Sensitivity and Resistance," New Trends in Antibiotics: Research and Therapy, Elsevier/North-Holland Biomedical Press, 1981, pp. 27-44; Chopra et al., "The tetracyclines: prospects at the beginning of the 1980's," Journal of Antimicrobial Chemotherapy, 8:5-21, (1981,) which are incorporated herein by reference. Web site: http://www.delphion.com/details?pn=US05258372__ •
Tetracycline antibiotic compositions Inventor(s): Armstrong; William W. (Mill Neck, NY) Assignee(s): Pfizer Inc. (New York, NY) Patent Number: 4,126,680 Date filed: April 27, 1977 Abstract: Aqueous solutions of oxytetracycline, doxycycline or chlortetracycline in caprolactam or 2-piperidone are disclosed. Excerpt(s): This invention relates to antibiotic compositions suitable for pharmaceutical use. More particularly, it relates to aqueous solutions of tetracycline antibiotics in caprolactam or 2-piperidone. U.S. Pat. No. 3,957,980 discloses aqueous injectable solutions of doxycycline comprising a solution in water of from about 1% to 10% by weight of doxycycline, together with about 3 to 8 molar proportions of a phosphate salt selected from phosphoric acid, sodium or potassium orthophosphate, metaphosphate, pyrophosphate, tripolyphosphate or hexametaphosphate, and about 3 to 8 molar proportions of a pharmaceutically acceptable magnesium salt solution in said aqueous pharmaceutical composition, said composition having a pH value in the range of from about 1 to 3.5. U.S. Pat. No. 3,674,859 discloses aqueous solutions of doxycycline containing from about 1% to 15% doxycycline and from about 5 percent to 40 percent by weight of polyvinylpyrrolidone having an average molecular weight that is in the range of from about 10,000 to about 60,000, said composition having a pH value in the range of from about 5 to about 8. Web site: http://www.delphion.com/details?pn=US04126680__
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Tetracycline--doxycycline antibiotic composition Inventor(s): Isbister; James D. (Potamac, MD), Rudnic; Edward M. (N. Potomac, MD), Treacy, Jr.; Donald J. (Arnold, MD), Wassink; Sandra E. (Frederick, MD) Assignee(s): Advancis Pharmaceutical Corp. (Gaithersburg, MD) Patent Number: 6,638,532 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 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. The present invention is directed to a new and improved composition that delivers two or more antibiotics, and the use thereof, with the two antibiotics being Tetracycline and Doxycycline. Web site: http://www.delphion.com/details?pn=US06638532__
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Use of tetracycline to enhance bone protein synthesis and/or treatment of osteoporosis Inventor(s): Golub; Lorne M. (Smithtown, NY), McNamara; Thomas F. (Port Jefferson, NY), Ramamurthy; Nungavaram S. (Smithtown, NY) Assignee(s): The Research Foundation of State University of New York (Albany, NY) Patent Number: 4,925,833 Date filed: December 29, 1986 Abstract: Tetracyclines, antibacterial and non-antibacterial tetracyclines, have been found to be useful in the treatment of osteoporosis in humans by administering to the human suffering from osteoporosis an effective amount of a tetracycline to enhance bone protein synthesis. Tetracyclines which have been found to be effective in the treatment of osteoporosis in humans include minocycline, doxycycline and dedimethylaminotetracyline. Excerpt(s): In pending U.S. patent application Ser. No. 566,517, now U.S. Pat. No. 4,666,897, it is disclosed that tetracyclines, such as the antibiotic tetracyclines, e.g tetracycline, are useful as anti-collagenolytic agents or as inhibitors of collagenase. These tetracyclines and compositions containing the same are disclosed therein as being useful in the treatment of periodontal diseases, corneal ulcers, rheumatoid arthritis and the like characterized by excessive collagen destruction. In pending U.S. patent application Ser. No. 699,048, now U.S. Pat. No. 4,704,383, it is disclosed that the non-antibiotic or nonantibacterial tetracyclines also possess anti-collagenolytic properties and are useful as inhibitors of collagenase. Additionally, these non-antibiotic or non-antibacterial tetracyclines have also been found to be useful in the treatment of periodontal diseases, corneal ulcers, bone deficiency disorders due to excess collagenase production or excessivde collagen destruction, rheumatoid arthristis and the like. A particularly useful non-antibiotic tetracycline in the practices of this invention is the tetracycline
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dedimethylaminotetracycline. Tetracyclines are useful as broad spectrum antibiotics because they have the ability to inhibit 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 inhibit 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. Web site: http://www.delphion.com/details?pn=US04925833__ •
Water-soluble derivative of 6-deoxy-tetracyclines Inventor(s): Cotti; Gino (Monza (Milan) Assignee(s): Ankerfarm, S.p.A. (Milan, IT) Patent Number: 4,060,605 Date filed: September 25, 1975 Abstract: This invention relates to a novel water soluble derivatives of 6-deoxytetracyclines, particularly of doxycycline, in which a methionine group is linked to the tetracycline group through a methylene bridge, thus obtaining a derivative which is not only water soluble at neutral pH, but also endowed with outstanding properties from the point of view of the therapeutical use. Excerpt(s): The new derivative forming subject matter of the invention is characterized by great solubility in water at neutral pH, and it can therefore be administered both per os and intramuscularly or intravenously and, in addition, preserves unaltered the antibiotic activity of deoxycycline. The new derivative has improved patient-toleration, stability and higher blood levels as compared with both the 6-deoxy-tetracyclines and with their water soluble derivatives; furthermore, its toxicity is lower even if it maintains unaltered the antibiotic properties of the 6-deoxy-tetracyclines. The product having the general formula I can be prepared by placing a compound of the group of the 6-deoxy-tetracyclines into contact with an equimolecular quantity of methionine, in the presence of formic aldehyde, in a polar solvent, at the temperatures and for the periods of time necessary to obtain a complete reaction. Web site: http://www.delphion.com/details?pn=US04060605__
Patent Applications on Doxycycline As of December 2000, U.S. patent applications are open to public viewing.10 Applications are patent requests which have yet to be granted. (The process to achieve a patent can take several years.) The following patent applications have been filed since December 2000 relating to doxycycline:
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This has been a common practice outside the United States prior to December 2000.
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DNA cassette for the production of secretable recombinant trimeric TRAIL proteins, tetracycline/ doxycycline-inducible adeno-associated virus vector, their combination and use in gene therapy Inventor(s): Billiar, Timothy R.; (Nevillewood, PA), Seol, Dai-Wu; (Geoje-si, KR) Correspondence: Klauber & Jackson; 411 Hackensack Avenue; Hackensack; NJ; 07601 Patent Application Number: 20020128438 Date filed: July 6, 2001 Abstract: The present invention relates to the construction of a TRAIL DNA cassette for the production of a secretable trimeric rTRAIL, the development of pCMVdw vectors and pAAVdw vectors harboring a feed-forward amplification loop type Tet-On system that can be packaged into AAV particles, the preparation of a recombinant vectors by the combination of the TRAIL DNA cassette and the two vectors, and the treatment of diseases including cancer using such vectors.The present invention provides a TRAIL DNA cassette comprising a secretion signal (SS) sequence, a trimer-forming domain (TFD) and a TRAIL(114-281) coding cDNA.The TRAIL cassette thus constructed can be cloned into an appropriate expression vector, and subsequently used in the mass production of a secretable recombinant trimeric TRAIL protein or administered to a patient for a gene therapy. Excerpt(s): The present invention relates to the construction of a DNA cassette for the production of secretable recombinant proteins, the development of Tetracycline/Doxycycline-inducible Adeno-associated virus vectors, recombinant vectors obtained by the combination of the DNA cassette and the vector, and a gene therapy using these vectors. Specifically, the present invention relates to the construction of a TRAIL DNA cassette for the production of a secretable trimeric rTRAIL, the development of pCMVdw vectors and pAAVdw vectors harboring a feedforward amplification loop type Tet-On system that can be packaged into AAV particles, the preparation of recombinant vectors by the combination of the TRAIL DNA cassette and the two vectors, and the treatment of diseases including cancer using such vectors. Apoptosis, also known as programmed cell death, is an evolutionarily conserved and genetically regulated biological process, and plays an important role in the development and homeostasis of multicellular organisms (Ashkenazi, A. & Dixit, V. M., Death receptors: signaling and modulation, Science 281, 1305-1308 (1998); Nagata, S., Apoptosis by death factor, Cell 88, 355-365 (1997); Salvesen, G. S. & Dixit, V. M., Caspases: intracellular signaling by proteolysis. Cell 91, 443-446 (1997)). Web site: http://appft1.uspto.gov/netahtml/PTO/search-bool.html
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Film-coated tablet for improved upper gastrointestinal tract safety Inventor(s): Bekker, Petrus Jakobus; (Mason, OH), Dansereau, Richard John; (Mason, OH) Correspondence: The Procter & Gamble Company; Intellectual Property Division; Winton Hill Technical Center - Box 161; 6110 Center Hill Avenue; Cincinnati; OH; 45224; US Patent Application Number: 20030211156 Date filed: March 28, 2003
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Abstract: A novel oral dosage to be delivered to the stomach comprising a safe and effective amount of an active ingredient selected from the group consisting of emepronium bromidebromide, doxycycline, and other tetracyclines/antibiotics, iron preparations, quinidine, nonsteroidal anti-inflammatory drugs, alprenolol, ascorbic acid, captopril, theophylline, zidovoudine (AZT), bisphosphonates and mixtures thereof and pharmaceutically-acceptable excipients, wherein said oral dosage form is a generally oval form and film coated to facilitate rapid esophageal transit and avoid irritation in the mouth, buccal cavity, pharynx, and esophagus. Excerpt(s): This application claims priority under Title 35, United States code 119(e) from Provisional Application Serial No. 60/049,306 filed Jun. 11, 1997. The present invention relates to novel oral dosage forms that protect the epithelial and mucosal tissues of the mouth and the buccal cavity, the pharynx, the larynx, and the esophagus from erosion, ulceration, or other like irritation suffered by direct contact of these tissues with the active ingredient. The tablet is a modified oval shape and is film coated. This invention further relates to a method of treating or preventing diseases characterized by abnormal calcium and phosphate metabolism using the novel film coated dosage forms described herein. The oral administration of certain active ingredients sometimes results in patient complaints shortly after dosing; said complaints are usually characterized by the patients as heartburn, esophageal burning, pain and/or difficulty upon swallowing, and/or pain existing behind and/or mid-sternum. It is believed that these complaints originate from esophagitis or esophageal irritation caused by the erosion, ulceration, or other like irritation of the epithelial and mucosal tissues of the upper gastrointestinal tract, generally the mouth through the stomach, most generally the esophagus. It is hypothesized that said irritation results from the active ingredient coming in direct contact with those epithelial and mucosal tissues, resulting in the topical irritation thereof. If the dosage form adheres in the esophagus, the active ingredient slowly dissolves and creates a high drug concentration on the mucosal surface of the esophagus. Web site: http://appft1.uspto.gov/netahtml/PTO/search-bool.html •
Metalloproteinase inhibitors for the treatment of respiratory diseases Inventor(s): Bannister, Robin Mark; (Essex, GB), Chaplin, Sharon Adele; (Essex, GB), McGlashan Richards, Andrew John; (Essex, GB) Correspondence: Saliwanchik Lloyd & Saliwanchik; A Professional Association; 2421 N.W. 41st Street; Suite A-1; Gainesville; FL; 326066669 Patent Application Number: 20030099600 Date filed: August 23, 2002 Abstract: Doxycycline is useful for the treatment of a respiratory disease involving tissue destruction. Excerpt(s): This Application is a continuation-in-part of PCT/GB01/00814, filed Feb. 26, 2001. This invention relates to the treatment of respiratory diseases. Many respiratory diseases have acute components, which include reduction of gaseous exchange due to acute effects involving constriction of the airways. This may be due to infection, bronchoconstriction, excess mucous and other mechanisms. In addition, this is often accompanied by a more serious and irreversible destruction of lung tissue. These effects combined lead to a steady loss of lung function, resulting in lower quality of life and
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shortened life expectancy. Such diseases include chronic obstructive pulmonary disease (COPD), chronic bronchitis, emphysema, asthma, cystic fibrosis (CF) and lung cancer. Web site: http://appft1.uspto.gov/netahtml/PTO/search-bool.html •
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. 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
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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 antibiotic product, use and formulation thereof 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: Carella, Byrne Bain, Gilfillan,; Cecchi, Stewart& Olstein; Six Becker Farm Road; Roseland; NJ; 07068; US Patent Application Number: 20020136766 Date filed: December 20, 2001 Abstract: An antibiotic product, in particular a tetracycline, such as doxycycline, is comprised of at least three dosages forms, each of which has a different release profile, with the C.sub.max for the antibiotic product being reached in less than about twelve hours. In one embodiment, there is an immediate release dosage form, as well as two or more delayed release dosage forms, with each of the dosage forms having a different release profile, wherein each reaches a C.sub.max at different times. Excerpt(s): This application is a continuation-in-part of U.S. application Ser. No. 09/792,092, filed on Feb. 22, 2000, which is a continuation-in-part of U.S. application Ser. No. 09/687,229, filed on Oct. 13, 2000, and also claims the priority of U.S. Provisional Application Serial No. 60/184,546 filed on Feb. 24, 2000. This invention relates to an antibiotic product, as well as the use and formulation thereof. The invention further relates to a tetracycline antibiotic product and in particular doxycycline and its derivatives, salts, hydrates, esters, metabolites, etc. A wide variety of antibiotics have been used, and will be used, in order to combat bacterial infection. In general, such antibiotics can be administered by a repeated dosing of immediate release dosage forms, which results in poor compliance or as a controlled release formulation (slow release) at
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higher administered doses. The present invention is directed to providing for an improved antibiotic product. Web site: http://appft1.uspto.gov/netahtml/PTO/search-bool.html •
Use of doxycycline for treatment of certain skin and mouth ailments Inventor(s): Heesch, Gary V.; (Salt Lake City, UT) Correspondence: Foster & Foster Llc; MR. Lynn G. Foster; 602 E. 300 S.; Salt Lake City; UT; 84102; US Patent Application Number: 20030092682 Date filed: July 20, 2001 Abstract: A method of treating (a) cold sores in and out of the mouth, (b) canker sores, (c) cancer wounds including but not limited to wounds such as those which fail to heal due to chemotherapy and radiation therapy, (d) surgical wounds of all types, (e) diabetes wounds, (f) decubitus ulcers, (g) athletes foot including chronic athletes foot and (h) scarring with doxycycline and/or cefaclor is disclosed. Excerpt(s): The present invention relates generally to the treatment of skin and mouth disorders and, more particularly, to the use of doxycycline and/or cefaclor to eradicate or significantly alleviate certain skin disorders. In the past, it has been difficult and often impossible to eradicate certain skin and mouth disorders, including various types of sores, wounds, skin ulcers, scarring and severe chronic athletes foot and infections. Most often, if not always, treatments of the past have either failed to cure the disorder or only offered temporary relief followed by reoccurrence of the ailment. The skin disorders in question comprise cold sores in and out of the mouth, canker sores, cancer wounds including surgical wounds (which fail to heal due to chemotherapy and radiation therapy), other types of surgical wounds, diabetes sores, decubitus ulcers, sores, scarring and athletes foot including chronic athletes foot. Web site: http://appft1.uspto.gov/netahtml/PTO/search-bool.html
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Viral replicons and viruses dependent on inducing agents Inventor(s): Berkhout, Benjamin; (Naarden, NL), Verhoef, Koenraad Dirk; (Witney Oxon, GB) Correspondence: Trask Britt; P.O. Box 2550; Salt Lake City; UT; 84110; US Patent Application Number: 20030099613 Date filed: March 8, 2002 Abstract: An inducible viral replicon comprising at least one inducible repressor and/or activator, and all viral sequences which are essential for replication under direct or indirect control of said inducible repressor and/or activator. The inducible repressor and/or activator may comprise a Tet operon. A replicon of the invention may be used to produce a virus, for instance an attenuated HIV virus, which can be induced to replicate by the presence of doxycycline or a functional analog thereof. The replicon and/or the produced virus may be used to prepare a vaccine, for instance for the prophylaxis of AIDS. A replicon of the invention can be modified, preferably improved, by culturing the replicon in permissive cells for an extended period of time.
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Excerpt(s): This application is a continuation of co-pending International Application No. PCT/NL00/00637, filed Sep. 8, 2000, designating the United States of America and corresponding to International Publication No. WO 01/20013 A2, the contents of the entirety of which are incorporated by this reference, which itself claims priority from EP 99202971.0, filed on Sep. 10, 1999. The present invention relates to the field of molecular biology of pathogens, in particular viruses, and more in particular to human immunodeficiency virus. It relates to methods for producing replicons and/or viruses dependent on inducing agents, the replicons and/or viruses, as well as uses of such replicons and/or viruses in the production of vaccines, and in particular to liveattenuated vaccines. Live-attenuated virus vaccines (such as vaccinia, polio and measles) have been enormously successful and have made a dramatic and historic impact on public health. However, for the human immunodeficiency virus type 1 (HIV-1), safety concerns remain about either the reversion of attenuated vaccine strains to virulent phenotypes or the induction of fulminant infection in immunocompromised individuals. 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 doxycycline, 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 “doxycycline” (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 doxycycline. You can also use this procedure to view pending patent applications concerning doxycycline. 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 DOXYCYCLINE Overview This chapter provides bibliographic book references relating to doxycycline. In addition to online booksellers such as www.amazon.com and www.bn.com, excellent sources for book titles on doxycycline include the Combined Health Information Database and the National Library of Medicine. Your local medical library also may have these titles available for loan.
The National Library of Medicine Book Index The National Library of Medicine at the National Institutes of Health has a massive database of books published on healthcare and biomedicine. Go to the following Internet site, http://locatorplus.gov/, and then select “Search LOCATORplus.” Once you are in the search area, simply type “doxycycline” (or synonyms) into the search box, and select “books only.” From there, results can be sorted by publication date, author, or relevance. The following was recently catalogued by the National Library of Medicine:11 •
Distribution of penicillin G, ampicillin, cloxacillin, tetracycline and doxycycline in the rabbit eye Author: Salminen, Lotta.; Year: 1976; Turku [Finland: s.n.], 1973; ISBN: 9519901299
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Doxycycline revisited: proceedings of a symposium held in New York, NY, 9 October 1987 Author: Norrby, Ragnar.; Year: 1988; Täby, Sweden: Pfizer AB, c1988
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Sexually transmitted diseases: reappraisal of the role of vibramycin: (doxycycline) Author: Fair, William R.; Year: 1975; New York: Pfizer Laboratories Division, Pfizer, inc., c1979
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In addition to LOCATORPlus, in collaboration with authors and publishers, the National Center for Biotechnology Information (NCBI) is currently adapting biomedical books for the Web. The books may be accessed in two ways: (1) by searching directly using any search term or phrase (in the same way as the bibliographic database PubMed), or (2) by following the links to PubMed abstracts. Each PubMed abstract has a "Books" button that displays a facsimile of the abstract in which some phrases are hypertext links. These phrases are also found in the books available at NCBI. Click on hyperlinked results in the list of books in which the phrase is found. Currently, the majority of the links are between the books and PubMed. In the future, more links will be created between the books and other types of information, such as gene and protein sequences and macromolecular structures. See http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=Books.
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Symposium on Doxycycline, held in Brussels, April 2-3, 1976 Author: Norrby, Ragnar.; Year: 1979; Stockholm: Distributed by Almqvist; Wiksell, 1976
Chapters on Doxycycline In order to find chapters that specifically relate to doxycycline, an excellent source of abstracts is the Combined Health Information Database. You will need to limit your search to book chapters and doxycycline 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 “doxycycline” (or synonyms) into the “For these words:” box. The following is a typical result when searching for book chapters on doxycycline: •
Antibiotics in Periodontal Therapy 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. 113-126. 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 antibiotics for the treatment of periodontal disease is from a textbook that integrates basic facts and principles of antibiotic therapy with recentlyemerged concepts of care. The authors note that in general, antibiotics are seldom necessary for treatment of gingivitis (gum inflammation) and chronic periodontal diseases. Scaling, root planing, and periodontal surgery (if indicated) are anti-infective measures that may negate the need for antibiotics. The authors discuss conditions that may call for systemic antimicrobial periodontal therapy, the infecting microorganisms, and the use of antibiotics in situations of plaque formation and gingivitis and periodontitis, and the selection of antibiotic regimens in periodontal therapy (single drug regimens, combination antimicrobial therapy, and sequential regimens). Specific drugs covered are penicillins, tetracyclines, minocycline, doxycycline, metronidazole, clindamycin, ciprofloxin, spiramycin, and amoxicillin and clavulanic acid. Important principles, key facts, and clinical insights are highlighted and the chapter concludes with a list of references. 3 figures. 2 tables. 58 references.
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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
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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 7. MULTIMEDIA ON DOXYCYCLINE Overview In this chapter, we show you how to keep current on multimedia sources of information on doxycycline. We start with sources that have been summarized by federal agencies, and then show you how to find bibliographic information catalogued by the National Library of Medicine.
Bibliography: Multimedia on Doxycycline The National Library of Medicine is a rich source of information on healthcare-related multimedia productions including slides, computer software, and databases. To access the multimedia database, go to the following Web site: http://locatorplus.gov/. Select “Search LOCATORplus.” Once in the search area, simply type in doxycycline (or synonyms). Then, in the option box provided below the search box, select “Audiovisuals and Computer Files.” From there, you can choose to sort results by publication date, author, or relevance. The following multimedia has been indexed on doxycycline: •
Intractable chylous ascites treated by intra cystic injection of doxycycline [videorecording] Source: from the Film Library and the Clinical Congress of ACS, Espace Video, Université Claude Bernard; Year: 2000; Format: Videorecording; [Woodbury, Conn.]: Ciné-Med, [2000]
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Use of a bioabsorbable drug delivery system in local drug delivery of doxycycline hyclate to treat periodontitis [videorecording] Source: University of Southern California, 23rd Annual Periodontal Symposium, February 7 and 8, 1997, Los Angeles Omni Hotel; by A; Year: 1997; Format: Videorecording; [United States]: A-V Health Promotions, c1997
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CHAPTER 8. PERIODICALS AND NEWS ON DOXYCYCLINE Overview In this chapter, we suggest a number of news sources and present various periodicals that cover doxycycline.
News Services and Press Releases One of the simplest ways of tracking press releases on doxycycline 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 “doxycycline” (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 doxycycline. 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 “doxycycline” (or synonyms). The following was recently listed in this archive for doxycycline: •
Doxycycline levels correlate with clearing of antibody in Q fever endocarditis Source: Reuters Medical News Date: November 24, 2003
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Very low-dose doxycycline effective for periodontitis in diabetics Source: Reuters Industry Breifing Date: March 17, 2003
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Intravenous doxycycline not useful for rheumatoid arthritis Source: Reuters Industry Breifing Date: January 22, 2003
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Chronic reactive arthritis does not respond to long-term doxycycline Source: Reuters Industry Breifing Date: November 28, 2001
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FDA suggests doxycycline, penicillin G procaine doses for inhalation anthrax Source: Reuters Medical News Date: October 30, 2001
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Atrix gets okay to market Atridox in Switzerland Source: Reuters Industry Breifing Date: July 03, 2001
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Single dose of doxycycline may prevent development of Lyme disease Source: Reuters Industry Breifing Date: June 12, 2001
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Atrix gets nod to market Atridox in Germany, Denmark and Sweden Source: Reuters Industry Breifing Date: May 03, 2001
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Atrix settles Atridox dispute with Block Drug Source: Reuters Industry Breifing Date: April 25, 2001
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FDA approves Par's generic doxycycline Source: Reuters Industry Breifing Date: December 19, 2000
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Doxycycline may have role as adjuvant therapy in lung cancer Source: Reuters Medical News Date: November 05, 1999
•
Doxycycline a possible treatment for abdominal aneurysms Source: Reuters Medical News Date: June 09, 1999
•
Doxycycline inhibits key enzymes involved in osteoarthritis Source: Reuters Medical News Date: April 14, 1999
•
Oral doxycycline effective against Lyme neuroborreliosis Source: Reuters Medical News Date: March 19, 1999
•
FDA approves low-dose doxycycline for gum disease Source: Reuters Medical News Date: October 02, 1998
•
Oral Doxycycline Is Effective Against Acute Disseminated Lyme Disease Source: Reuters Medical News Date: July 31, 1997
•
Doxycycline During Pregnancy Not A Major Teratogenic Risk Factor Source: Reuters Medical News Date: April 01, 1997
Periodicals and News
•
Atrix's Atridox Periodontal Treatment Successful In Phase III Trials Source: Reuters Medical News Date: March 24, 1997
•
Doxycycline, Quinolones And Rifamycins: Effective Against Human Granulocytic Ehrlichiosis Source: Reuters Medical News Date: January 06, 1997
•
Bleomycin Better Than Doxycycline For Pericardial Sclerotherapy Source: Reuters Medical News Date: December 13, 1996
•
Doxycycline Effective In Veterans With Gulf War Syndrome Source: Reuters Medical News Date: January 04, 1996
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The NIH Within MEDLINEplus, the NIH has made an agreement with the New York Times Syndicate, the AP News Service, and Reuters to deliver news that can be browsed by the public. Search news releases at http://www.nlm.nih.gov/medlineplus/alphanews_a.html. MEDLINEplus allows you to browse across an alphabetical index. Or you can search by date at the following Web page: http://www.nlm.nih.gov/medlineplus/newsbydate.html. Often, news items are indexed by MEDLINEplus within its search engine. Business Wire Business Wire is similar to PR Newswire. To access this archive, simply go to http://www.businesswire.com/. You can scan the news by industry category or company name. Market Wire Market Wire is more focused on technology than the other wires. To browse the latest press releases by topic, such as alternative medicine, biotechnology, fitness, healthcare, legal, nutrition, and pharmaceuticals, access Market Wire’s Medical/Health channel at http://www.marketwire.com/mw/release_index?channel=MedicalHealth. Or simply go to Market Wire’s home page at http://www.marketwire.com/mw/home, type “doxycycline” (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 “doxycycline” (or synonyms). If you know the name of a company that is relevant to
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doxycycline, 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 “doxycycline” (or synonyms).
Academic Periodicals covering Doxycycline Numerous periodicals are currently indexed within the National Library of Medicine’s PubMed database that are known to publish articles relating to doxycycline. In addition to these sources, you can search for articles covering doxycycline 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 9. 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 doxycycline. 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 doxycycline. 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 doxycycline: 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
Tetracyclines •
Systemic - U.S. Brands: Achromycin V; Minocin; Terramycin; Vibramycin http://www.nlm.nih.gov/medlineplus/druginfo/uspdi/202552.html
Commercial Databases In addition to the medications listed in the USP above, a number of commercial sites are available by subscription to physicians and their institutions. Or, you may be able to access these sources from your local medical library.
Mosby’s Drug Consult Mosby’s Drug Consult database (also available on CD-ROM and book format) covers 45,000 drug products including generics and international brands. It provides prescribing information, drug interactions, and patient information. Subscription information is available at the following hyperlink: http://www.mosbysdrugconsult.com/. PDRhealth The PDRhealth database is a free-to-use, drug information search engine that has been written for the public in layman’s terms. It contains FDA-approved drug information adapted from the Physicians’ Desk Reference (PDR) database. PDRhealth can be searched by brand name, generic name, or indication. It features multiple drug interactions reports. Search PDRhealth at http://www.pdrhealth.com/drug_info/index.html. Other Web Sites Drugs.com (www.drugs.com) reproduces the information in the Pharmacopeia as well as commercial information. You may also want to consider the Web site of the Medical Letter, Inc. (http://www.medletter.com/) which allows users to download articles on various drugs and therapeutics for a nominal fee. If you have any questions about a medical treatment, the FDA may have an office near you. Look for their number in the blue pages of the phone book. You can also contact the FDA through its toll-free number, 1-888-INFO-FDA (1-888-463-6332), or on the World Wide Web at www.fda.gov.
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APPENDICES
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APPENDIX A. PHYSICIAN RESOURCES Overview In this chapter, we focus on databases and Internet-based guidelines and information resources created or written for a professional audience.
NIH Guidelines Commonly referred to as “clinical” or “professional” guidelines, the National Institutes of Health publish physician guidelines for the most common diseases. Publications are available at the following by relevant Institute12: •
Office of the Director (OD); guidelines consolidated across agencies available at http://www.nih.gov/health/consumer/conkey.htm
•
National Institute of General Medical Sciences (NIGMS); fact sheets available at http://www.nigms.nih.gov/news/facts/
•
National Library of Medicine (NLM); extensive encyclopedia (A.D.A.M., Inc.) with guidelines: http://www.nlm.nih.gov/medlineplus/healthtopics.html
•
National Cancer Institute (NCI); guidelines available at http://www.cancer.gov/cancerinfo/list.aspx?viewid=5f35036e-5497-4d86-8c2c714a9f7c8d25
•
National Eye Institute (NEI); guidelines available at http://www.nei.nih.gov/order/index.htm
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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
•
National Institute on Aging (NIA); guidelines available at http://www.nia.nih.gov/health/
12
These publications are typically written by one or more of the various NIH Institutes.
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•
National Institute on Alcohol Abuse and Alcoholism (NIAAA); guidelines available at http://www.niaaa.nih.gov/publications/publications.htm
•
National Institute of Allergy and Infectious Diseases (NIAID); guidelines available at http://www.niaid.nih.gov/publications/
•
National Institute of Arthritis and Musculoskeletal and Skin Diseases (NIAMS); fact sheets and guidelines available at http://www.niams.nih.gov/hi/index.htm
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National Institute of Child Health and Human Development (NICHD); guidelines available at http://www.nichd.nih.gov/publications/pubskey.cfm
•
National Institute on Deafness and Other Communication Disorders (NIDCD); fact sheets and guidelines at http://www.nidcd.nih.gov/health/
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National Institute of Dental and Craniofacial Research (NIDCR); guidelines available at http://www.nidr.nih.gov/health/
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National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK); guidelines available at http://www.niddk.nih.gov/health/health.htm
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National Institute on Drug Abuse (NIDA); guidelines available at http://www.nida.nih.gov/DrugAbuse.html
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National Institute of Environmental Health Sciences (NIEHS); environmental health information available at http://www.niehs.nih.gov/external/facts.htm
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National Institute of Mental Health (NIMH); guidelines available at http://www.nimh.nih.gov/practitioners/index.cfm
•
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
•
National Institute of Nursing Research (NINR); publications on selected illnesses at http://www.nih.gov/ninr/news-info/publications.html
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National Institute of Biomedical Imaging and Bioengineering; general information at http://grants.nih.gov/grants/becon/becon_info.htm
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Center for Information Technology (CIT); referrals to other agencies based on keyword searches available at http://kb.nih.gov/www_query_main.asp
•
National Center for Complementary and Alternative Medicine (NCCAM); health information available at http://nccam.nih.gov/health/
•
National Center for Research Resources (NCRR); various information directories available at http://www.ncrr.nih.gov/publications.asp
•
Office of Rare Diseases; various fact sheets available at http://rarediseases.info.nih.gov/html/resources/rep_pubs.html
•
Centers for Disease Control and Prevention; various fact sheets on infectious diseases available at http://www.cdc.gov/publications.htm
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NIH Databases In addition to the various Institutes of Health that publish professional guidelines, the NIH has designed a number of databases for professionals.13 Physician-oriented resources provide a wide variety of information related to the biomedical and health sciences, both past and present. The format of these resources varies. Searchable databases, bibliographic citations, full-text articles (when available), archival collections, and images are all available. The following are referenced by the National Library of Medicine:14 •
Bioethics: Access to published literature on the ethical, legal, and public policy issues surrounding healthcare and biomedical research. This information is provided in conjunction with the Kennedy Institute of Ethics located at Georgetown University, Washington, D.C.: http://www.nlm.nih.gov/databases/databases_bioethics.html
•
HIV/AIDS Resources: Describes various links and databases dedicated to HIV/AIDS research: http://www.nlm.nih.gov/pubs/factsheets/aidsinfs.html
•
NLM Online Exhibitions: Describes “Exhibitions in the History of Medicine”: http://www.nlm.nih.gov/exhibition/exhibition.html. Additional resources for historical scholarship in medicine: http://www.nlm.nih.gov/hmd/hmd.html
•
Biotechnology Information: Access to public databases. The National Center for Biotechnology Information conducts research in computational biology, develops software tools for analyzing genome data, and disseminates biomedical information for the better understanding of molecular processes affecting human health and disease: http://www.ncbi.nlm.nih.gov/
•
Population Information: The National Library of Medicine provides access to worldwide coverage of population, family planning, and related health issues, including family planning technology and programs, fertility, and population law and policy: http://www.nlm.nih.gov/databases/databases_population.html
•
Cancer Information: Access to cancer-oriented databases: http://www.nlm.nih.gov/databases/databases_cancer.html
•
Profiles in Science: Offering the archival collections of prominent twentieth-century biomedical scientists to the public through modern digital technology: http://www.profiles.nlm.nih.gov/
•
Chemical Information: Provides links to various chemical databases and references: http://sis.nlm.nih.gov/Chem/ChemMain.html
•
Clinical Alerts: Reports the release of findings from the NIH-funded clinical trials where such release could significantly affect morbidity and mortality: http://www.nlm.nih.gov/databases/alerts/clinical_alerts.html
•
Space Life Sciences: Provides links and information to space-based research (including NASA): http://www.nlm.nih.gov/databases/databases_space.html
•
MEDLINE: Bibliographic database covering the fields of medicine, nursing, dentistry, veterinary medicine, the healthcare system, and the pre-clinical sciences: http://www.nlm.nih.gov/databases/databases_medline.html
13
Remember, for the general public, the National Library of Medicine recommends the databases referenced in MEDLINEplus (http://medlineplus.gov/ or http://www.nlm.nih.gov/medlineplus/databases.html). 14 See http://www.nlm.nih.gov/databases/databases.html.
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•
Toxicology and Environmental Health Information (TOXNET): Databases covering toxicology and environmental health: http://sis.nlm.nih.gov/Tox/ToxMain.html
•
Visible Human Interface: Anatomically detailed, three-dimensional representations of normal male and female human bodies: http://www.nlm.nih.gov/research/visible/visible_human.html The Combined Health Information Database
A comprehensive source of information on clinical guidelines written for professionals is the Combined Health Information Database. You will need to limit your search to one of the following: Brochure/Pamphlet, Fact Sheet, or Information Package, and “doxycycline” using the “Detailed Search” option. Go directly to the following hyperlink: http://chid.nih.gov/detail/detail.html. To find associations, use the drop boxes at the bottom of the search page where “You may refine your search by.” For the publication date, select “All Years.” Select your preferred language and the format option “Fact Sheet.” Type “doxycycline” (or synonyms) into the “For these words:” box. The following is a sample result: •
HIV Treatment Strategy, Part III: Drug Information for People Living With AIDS Contact: Carl Vogel Center, 1012 14th St NW Ste 707, Washington, DC, 20005, (202) 6380750. Summary: This paper provides prescriptive drug treatment information for Persons With AIDS (PWA's). It is important for HIV-positive individuals to talk to a physician about a complete antiviral, immunomodulatory, and prophylactic drug program. Antivirals/antibiotics include AZT, ddc, and/or ddi; Combination of the three is thought to increase overall effectiveness. D4T either alone or with ddi looks promising. Many physicians include acyclovir to prevent HIV activation by herpes viruses. Some physicians recommend IV Compound Q for individuals with CD-4's over 100. Doxycycline is used as an anti-mycoplasma agent, Peptide-T seems most useful for neuropathy and cognitive dysfunction problems. Bitter melon is being tried with CD-4 increases is also looking promising. Some immune modulators include: Antioxidants, antabuse/disulfiram, coenzyme Q10, DNCB, glutathione, isoprinosine, naltrexone, pentoxifylline/trental, recombinant gp 160 vaccine, and thymus derivatives. Pap smears and vaginal exams should be conducted regularly for women. Extra nutrients for women should be implemented.
The NLM Gateway15 The NLM (National Library of Medicine) Gateway is a Web-based system that lets users search simultaneously in multiple retrieval systems at the U.S. National Library of Medicine (NLM). It allows users of NLM services to initiate searches from one Web interface, providing one-stop searching for many of NLM’s information resources or databases.16 To use the NLM Gateway, simply go to the search site at http://gateway.nlm.nih.gov/gw/Cmd. Type “doxycycline” (or synonyms) into the search box and click “Search.” The results will 15 16
Adapted from NLM: http://gateway.nlm.nih.gov/gw/Cmd?Overview.x.
The NLM Gateway is currently being developed by the Lister Hill National Center for Biomedical Communications (LHNCBC) at the National Library of Medicine (NLM) of the National Institutes of Health (NIH).
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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 5531 30 986 84 2 6633
HSTAT17 HSTAT is a free, Web-based resource that provides access to full-text documents used in healthcare decision-making.18 These documents include clinical practice guidelines, quickreference guides for clinicians, consumer health brochures, evidence reports and technology assessments from the Agency for Healthcare Research and Quality (AHRQ), as well as AHRQ’s Put Prevention Into Practice.19 Simply search by “doxycycline” (or synonyms) at the following Web site: http://text.nlm.nih.gov.
Coffee Break: Tutorials for Biologists20 Coffee Break is a general healthcare site that takes a scientific view of the news and covers recent breakthroughs in biology that may one day assist physicians in developing treatments. Here you will find a collection of short reports on recent biological discoveries. Each report incorporates interactive tutorials that demonstrate how bioinformatics tools are used as a part of the research process. Currently, all Coffee Breaks are written by NCBI staff.21 Each report is about 400 words and is usually based on a discovery reported in one or more articles from recently published, peer-reviewed literature.22 This site has new articles every few weeks, so it can be considered an online magazine of sorts. It is intended for general background information. You can access the Coffee Break Web site at the following hyperlink: http://www.ncbi.nlm.nih.gov/Coffeebreak/. 17
Adapted from HSTAT: http://www.nlm.nih.gov/pubs/factsheets/hstat.html.
18
The HSTAT URL is http://hstat.nlm.nih.gov/.
19
Other important documents in HSTAT include: the National Institutes of Health (NIH) Consensus Conference Reports and Technology Assessment Reports; the HIV/AIDS Treatment Information Service (ATIS) resource documents; the Substance Abuse and Mental Health Services Administration's Center for Substance Abuse Treatment (SAMHSA/CSAT) Treatment Improvement Protocols (TIP) and Center for Substance Abuse Prevention (SAMHSA/CSAP) Prevention Enhancement Protocols System (PEPS); the Public Health Service (PHS) Preventive Services Task Force's Guide to Clinical Preventive Services; the independent, nonfederal Task Force on Community Services’ Guide to Community Preventive Services; and the Health Technology Advisory Committee (HTAC) of the Minnesota Health Care Commission (MHCC) health technology evaluations. 20 Adapted from http://www.ncbi.nlm.nih.gov/Coffeebreak/Archive/FAQ.html. 21
The figure that accompanies each article is frequently supplied by an expert external to NCBI, in which case the source of the figure is cited. The result is an interactive tutorial that tells a biological story. 22 After a brief introduction that sets the work described into a broader context, the report focuses on how a molecular understanding can provide explanations of observed biology and lead to therapies for diseases. Each vignette is accompanied by a figure and hypertext links that lead to a series of pages that interactively show how NCBI tools and resources are used in the research process.
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Other Commercial Databases In addition to resources maintained by official agencies, other databases exist that are commercial ventures addressing medical professionals. Here are some examples that may interest you: •
CliniWeb International: Index and table of contents to selected clinical information on the Internet; see http://www.ohsu.edu/cliniweb/.
•
Medical World Search: Searches full text from thousands of selected medical sites on the Internet; see http://www.mwsearch.com/.
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APPENDIX B. PATIENT RESOURCES Overview Official agencies, as well as federally funded institutions supported by national grants, frequently publish a variety of guidelines written with the patient in mind. These are typically called “Fact Sheets” or “Guidelines.” They can take the form of a brochure, information kit, pamphlet, or flyer. Often they are only a few pages in length. Since new guidelines on doxycycline 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 doxycycline. 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 doxycycline. 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 “doxycycline”:
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•
Other guides Anthrax http://www.nlm.nih.gov/medlineplus/anthrax.html Bacterial Infections http://www.nlm.nih.gov/medlineplus/bacterialinfections.html Biodefense and Bioterrorism http://www.nlm.nih.gov/medlineplus/biodefenseandbioterrorism.html Lyme Disease http://www.nlm.nih.gov/medlineplus/lymedisease.html Malaria http://www.nlm.nih.gov/medlineplus/malaria.html Plague http://www.nlm.nih.gov/medlineplus/plague.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 doxycycline. 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: •
Chlamydia : Questions and Answers Contact: Planned Parenthood of Federation of America Incorporated, PO Box 4457, New York, NY, 10163-4457, (800) 669-0156, http://www.plannedparenthood.org. Summary: This brochure presents general information about chlamydia using a question and answer format. The brochure presents the general symptoms of chlamydia and methods of transmission including unprotected vaginal or anal sex. Chlamydia is the most common sexually transmitted disease (STD) in the United States (US), and can lead to the development of pelvic inflammatory disease (PID), a condition that can block fallopian tubes in women. The symptoms of PID in women include longer and/or heavier periods, more cramping during periods, abnormal mucus discharge, lower abdomen pain, tiredness, weakness, fever, vomiting, and/or pain during vaginal intercourse or a pelvic exam. Chlamydia also can cause sterility or Reiter's syndrome in men. Chlamydia can be passed to infants from their mothers during pregnancy or childbirth leading to neonatal conjunctivitis, chlamydia pneumonia, miscarriage, or stillbirth. It can be diagnosed through a cervical exam; lab tests of cells from the penis,
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cervix, urethra, or anus; or tests of urine samples. Chlamydia can be treated easily using antibiotics such as doxycycline, azithromycin, ofloxacin, erythromycin, or erythromycin ethylsuccinate. Persons with chlamydia should adhere to their medical regimen, undergo follow-up visits with their physicians, and get their partner(s) treated at the same time. Persons who have a number of different sex partners, who don't use condoms, or who have a history of other STDs are most likely to get chlamydia. Persons with chlamydia can avoid spreading their infection to others by informing their sex partners about their condition, avoiding sex until treatment is complete, getting their partners tested and treated at the same time, and using female or male condoms during each sexual activity. Persons can prevent getting chlamydia by practicing safer sex or abstaining from intercourse altogether. Birth control pills may increase women's chances for contracting this STD, therefore, they should also use a male or female condoms. Concerned individuals can get tested for chlamydia at Planned Parenthood centers, their doctors' offices, health departments, and clinics. •
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. Healthfinder™
Healthfinder™ is sponsored by the U.S. Department of Health and Human Services and offers links to hundreds of other sites that contain healthcare information. This Web site is located at http://www.healthfinder.gov. Again, keyword searches can be used to find guidelines. The following was recently found in this database:
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CDC Health Advisory: Use of Ciprofloxacin or Doxycycline for Postexposure Prophylaxis for Prevention of Inhalational Anthrax Summary: Interim recommendations for postexposure prophylaxis to prevent inhalational anthrax after exposure to B. Source: Centers for Disease Control and Prevention, U.S. Department of Health and Human Services http://www.healthfinder.gov/scripts/recordpass.asp?RecordType=0&RecordID=6366
•
Doxycycline and Penicillin G Procaine for Inhalational Anthrax (Post-Exposure) Summary: This drug information sheet from FDA's Center for Drug Evaluation and Research provides recommendations for the antibiotics doxycycline and penicillin G procaine for treatment of inhalational anthrax. Source: Center for Drug Evaluation and Research, U.S. Food and Drug Administration http://www.healthfinder.gov/scripts/recordpass.asp?RecordType=0&RecordID=6368
•
FDA Public Health Advisory: Update on Use of Doxycycline for Anthrax Exposure Summary: This FDA public health advisory provides dosing regimens for adults and children who may be treated with doxycycline for anthrax exposure. Source: U.S. Food and Drug Administration http://www.healthfinder.gov/scripts/recordpass.asp?RecordType=0&RecordID=6341 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 doxycycline. 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
Patient Resources
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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
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Finding Associations There are several Internet directories that provide lists of medical associations with information on or resources relating to doxycycline. By consulting all of associations listed in this chapter, you will have nearly exhausted all sources for patient associations concerned with doxycycline. 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 doxycycline. For more information, see the NHIC’s Web site at http://www.health.gov/NHIC/ or contact an information specialist by calling 1-800-336-4797. Directory of Health Organizations The Directory of Health Organizations, provided by the National Library of Medicine Specialized Information Services, is a comprehensive source of information on associations. The Directory of Health Organizations database can be accessed via the Internet at http://www.sis.nlm.nih.gov/Dir/DirMain.html. It is composed of two parts: DIRLINE and Health Hotlines. The DIRLINE database comprises some 10,000 records of organizations, research centers, and government institutes and associations that primarily focus on health and biomedicine. To access DIRLINE directly, go to the following Web site: http://dirline.nlm.nih.gov/. Simply type in “doxycycline” (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 “doxycycline”. 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
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option “Organization Resource Sheet.” Type “doxycycline” (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 “doxycycline” (or a synonym) into the search box, and click “Submit Query.”
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APPENDIX C. FINDING MEDICAL LIBRARIES Overview In this Appendix, we show you how to quickly find a medical library in your area.
Preparation Your local public library and medical libraries have interlibrary loan programs with the National Library of Medicine (NLM), one of the largest medical collections in the world. According to the NLM, most of the literature in the general and historical collections of the National Library of Medicine is available on interlibrary loan to any library. If you would like to access NLM medical literature, then visit a library in your area that can request the publications for you.23
Finding a Local Medical Library The quickest method to locate medical libraries is to use the Internet-based directory published by the National Network of Libraries of Medicine (NN/LM). This network includes 4626 members and affiliates that provide many services to librarians, health professionals, and the public. To find a library in your area, simply visit http://nnlm.gov/members/adv.html or call 1-800-338-7657.
Medical Libraries in the U.S. and Canada In addition to the NN/LM, the National Library of Medicine (NLM) lists a number of libraries with reference facilities that are open to the public. The following is the NLM’s list and includes hyperlinks to each library’s Web site. These Web pages can provide information on hours of operation and other restrictions. The list below is a small sample of
23
Adapted from the NLM: http://www.nlm.nih.gov/psd/cas/interlibrary.html.
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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)24: •
Alabama: Health InfoNet of Jefferson County (Jefferson County Library Cooperative, Lister Hill Library of the Health Sciences), http://www.uab.edu/infonet/
•
Alabama: Richard M. Scrushy Library (American Sports Medicine Institute)
•
Arizona: Samaritan Regional Medical Center: The Learning Center (Samaritan Health System, Phoenix, Arizona), http://www.samaritan.edu/library/bannerlibs.htm
•
California: Kris Kelly Health Information Center (St. Joseph Health System, Humboldt), http://www.humboldt1.com/~kkhic/index.html
•
California: Community Health Library of Los Gatos, http://www.healthlib.org/orgresources.html
•
California: Consumer Health Program and Services (CHIPS) (County of Los Angeles Public Library, Los Angeles County Harbor-UCLA Medical Center Library) - Carson, CA, http://www.colapublib.org/services/chips.html
•
California: Gateway Health Library (Sutter Gould Medical Foundation)
•
California: Health Library (Stanford University Medical Center), http://wwwmed.stanford.edu/healthlibrary/
•
California: Patient Education Resource Center - Health Information and Resources (University of California, San Francisco), http://sfghdean.ucsf.edu/barnett/PERC/default.asp
•
California: Redwood Health Library (Petaluma Health Care District), http://www.phcd.org/rdwdlib.html
•
California: Los Gatos PlaneTree Health Library, http://planetreesanjose.org/
•
California: Sutter Resource Library (Sutter Hospitals Foundation, Sacramento), http://suttermedicalcenter.org/library/
•
California: Health Sciences Libraries (University of California, Davis), http://www.lib.ucdavis.edu/healthsci/
•
California: ValleyCare Health Library & Ryan Comer Cancer Resource Center (ValleyCare Health System, Pleasanton), http://gaelnet.stmarysca.edu/other.libs/gbal/east/vchl.html
•
California: Washington Community Health Resource Library (Fremont), http://www.healthlibrary.org/
•
Colorado: William V. Gervasini Memorial Library (Exempla Healthcare), http://www.saintjosephdenver.org/yourhealth/libraries/
•
Connecticut: Hartford Hospital Health Science Libraries (Hartford Hospital), http://www.harthosp.org/library/
•
Connecticut: Healthnet: Connecticut Consumer Health Information Center (University of Connecticut Health Center, Lyman Maynard Stowe Library), http://library.uchc.edu/departm/hnet/
24
Abstracted from http://www.nlm.nih.gov/medlineplus/libraries.html.
Finding Medical Libraries
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•
Connecticut: Waterbury Hospital Health Center Library (Waterbury Hospital, Waterbury), http://www.waterburyhospital.com/library/consumer.shtml
•
Delaware: Consumer Health Library (Christiana Care Health System, Eugene du Pont Preventive Medicine & Rehabilitation Institute, Wilmington), http://www.christianacare.org/health_guide/health_guide_pmri_health_info.cfm
•
Delaware: Lewis B. Flinn Library (Delaware Academy of Medicine, Wilmington), http://www.delamed.org/chls.html
•
Georgia: Family Resource Library (Medical College of Georgia, Augusta), http://cmc.mcg.edu/kids_families/fam_resources/fam_res_lib/frl.htm
•
Georgia: Health Resource Center (Medical Center of Central Georgia, Macon), http://www.mccg.org/hrc/hrchome.asp
•
Hawaii: Hawaii Medical Library: Consumer Health Information Service (Hawaii Medical Library, Honolulu), http://hml.org/CHIS/
•
Idaho: DeArmond Consumer Health Library (Kootenai Medical Center, Coeur d’Alene), http://www.nicon.org/DeArmond/index.htm
•
Illinois: Health Learning Center of Northwestern Memorial Hospital (Chicago), http://www.nmh.org/health_info/hlc.html
•
Illinois: Medical Library (OSF Saint Francis Medical Center, Peoria), http://www.osfsaintfrancis.org/general/library/
•
Kentucky: Medical Library - Services for Patients, Families, Students & the Public (Central Baptist Hospital, Lexington), http://www.centralbap.com/education/community/library.cfm
•
Kentucky: University of Kentucky - Health Information Library (Chandler Medical Center, Lexington), http://www.mc.uky.edu/PatientEd/
•
Louisiana: Alton Ochsner Medical Foundation Library (Alton Ochsner Medical Foundation, New Orleans), http://www.ochsner.org/library/
•
Louisiana: Louisiana State University Health Sciences Center Medical LibraryShreveport, http://lib-sh.lsuhsc.edu/
•
Maine: Franklin Memorial Hospital Medical Library (Franklin Memorial Hospital, Farmington), http://www.fchn.org/fmh/lib.htm
•
Maine: Gerrish-True Health Sciences Library (Central Maine Medical Center, Lewiston), http://www.cmmc.org/library/library.html
•
Maine: Hadley Parrot Health Science Library (Eastern Maine Healthcare, Bangor), http://www.emh.org/hll/hpl/guide.htm
•
Maine: Maine Medical Center Library (Maine Medical Center, Portland), http://www.mmc.org/library/
•
Maine: Parkview Hospital (Brunswick), http://www.parkviewhospital.org/
•
Maine: Southern Maine Medical Center Health Sciences Library (Southern Maine Medical Center, Biddeford), http://www.smmc.org/services/service.php3?choice=10
•
Maine: Stephens Memorial Hospital’s Health Information Library (Western Maine Health, Norway), http://www.wmhcc.org/Library/
170 Doxycycline
•
Manitoba, Canada: Consumer & Patient Health Information Service (University of Manitoba Libraries), http://www.umanitoba.ca/libraries/units/health/reference/chis.html
•
Manitoba, Canada: J.W. Crane Memorial Library (Deer Lodge Centre, Winnipeg), http://www.deerlodge.mb.ca/crane_library/about.asp
•
Maryland: Health Information Center at the Wheaton Regional Library (Montgomery County, Dept. of Public Libraries, Wheaton Regional Library), http://www.mont.lib.md.us/healthinfo/hic.asp
•
Massachusetts: Baystate Medical Center Library (Baystate Health System), http://www.baystatehealth.com/1024/
•
Massachusetts: Boston University Medical Center Alumni Medical Library (Boston University Medical Center), http://med-libwww.bu.edu/library/lib.html
•
Massachusetts: Lowell General Hospital Health Sciences Library (Lowell General Hospital, Lowell), http://www.lowellgeneral.org/library/HomePageLinks/WWW.htm
•
Massachusetts: Paul E. Woodard Health Sciences Library (New England Baptist Hospital, Boston), http://www.nebh.org/health_lib.asp
•
Massachusetts: St. Luke’s Hospital Health Sciences Library (St. Luke’s Hospital, Southcoast Health System, New Bedford), http://www.southcoast.org/library/
•
Massachusetts: Treadwell Library Consumer Health Reference Center (Massachusetts General Hospital), http://www.mgh.harvard.edu/library/chrcindex.html
•
Massachusetts: UMass HealthNet (University of Massachusetts Medical School, Worchester), http://healthnet.umassmed.edu/
•
Michigan: Botsford General Hospital Library - Consumer Health (Botsford General Hospital, Library & Internet Services), http://www.botsfordlibrary.org/consumer.htm
•
Michigan: Helen DeRoy Medical Library (Providence Hospital and Medical Centers), http://www.providence-hospital.org/library/
•
Michigan: Marquette General Hospital - Consumer Health Library (Marquette General Hospital, Health Information Center), http://www.mgh.org/center.html
•
Michigan: Patient Education Resouce Center - University of Michigan Cancer Center (University of Michigan Comprehensive Cancer Center, Ann Arbor), http://www.cancer.med.umich.edu/learn/leares.htm
•
Michigan: Sladen Library & Center for Health Information Resources - Consumer Health Information (Detroit), http://www.henryford.com/body.cfm?id=39330
•
Montana: Center for Health Information (St. Patrick Hospital and Health Sciences Center, Missoula)
•
National: Consumer Health Library Directory (Medical Library Association, Consumer and Patient Health Information Section), http://caphis.mlanet.org/directory/index.html
•
National: National Network of Libraries of Medicine (National Library of Medicine) provides library services for health professionals in the United States who do not have access to a medical library, http://nnlm.gov/
•
National: NN/LM List of Libraries Serving the Public (National Network of Libraries of Medicine), http://nnlm.gov/members/
Finding Medical Libraries
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•
Nevada: Health Science Library, West Charleston Library (Las Vegas-Clark County Library District, Las Vegas), http://www.lvccld.org/special_collections/medical/index.htm
•
New Hampshire: Dartmouth Biomedical Libraries (Dartmouth College Library, Hanover), http://www.dartmouth.edu/~biomed/resources.htmld/conshealth.htmld/
•
New Jersey: Consumer Health Library (Rahway Hospital, Rahway), http://www.rahwayhospital.com/library.htm
•
New Jersey: Dr. Walter Phillips Health Sciences Library (Englewood Hospital and Medical Center, Englewood), http://www.englewoodhospital.com/links/index.htm
•
New Jersey: Meland Foundation (Englewood Hospital and Medical Center, Englewood), http://www.geocities.com/ResearchTriangle/9360/
•
New York: Choices in Health Information (New York Public Library) - NLM Consumer Pilot Project participant, http://www.nypl.org/branch/health/links.html
•
New York: Health Information Center (Upstate Medical University, State University of New York, Syracuse), http://www.upstate.edu/library/hic/
•
New York: Health Sciences Library (Long Island Jewish Medical Center, New Hyde Park), http://www.lij.edu/library/library.html
•
New York: ViaHealth Medical Library (Rochester General Hospital), http://www.nyam.org/library/
•
Ohio: Consumer Health Library (Akron General Medical Center, Medical & Consumer Health Library), http://www.akrongeneral.org/hwlibrary.htm
•
Oklahoma: The Health Information Center at Saint Francis Hospital (Saint Francis Health System, Tulsa), http://www.sfh-tulsa.com/services/healthinfo.asp
•
Oregon: Planetree Health Resource Center (Mid-Columbia Medical Center, The Dalles), http://www.mcmc.net/phrc/
•
Pennsylvania: Community Health Information Library (Milton S. Hershey Medical Center, Hershey), http://www.hmc.psu.edu/commhealth/
•
Pennsylvania: Community Health Resource Library (Geisinger Medical Center, Danville), http://www.geisinger.edu/education/commlib.shtml
•
Pennsylvania: HealthInfo Library (Moses Taylor Hospital, Scranton), http://www.mth.org/healthwellness.html
•
Pennsylvania: Hopwood Library (University of Pittsburgh, Health Sciences Library System, Pittsburgh), http://www.hsls.pitt.edu/guides/chi/hopwood/index_html
•
Pennsylvania: Koop Community Health Information Center (College of Physicians of Philadelphia), http://www.collphyphil.org/kooppg1.shtml
•
Pennsylvania: Learning Resources Center - Medical Library (Susquehanna Health System, Williamsport), http://www.shscares.org/services/lrc/index.asp
•
Pennsylvania: Medical Library (UPMC Health System, Pittsburgh), http://www.upmc.edu/passavant/library.htm
•
Quebec, Canada: Medical Library (Montreal General Hospital), http://www.mghlib.mcgill.ca/
172 Doxycycline
•
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
173
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
175
DOXYCYCLINE DICTIONARY The definitions below are derived from official public sources, including the National Institutes of Health [NIH] and the European Union [EU]. Abdomen: That portion of the body that lies between the thorax and the pelvis. [NIH] Abdominal: Having to do with the abdomen, which is the part of the body between the chest and the hips that contains the pancreas, stomach, intestines, liver, gallbladder, and other organs. [NIH] Abdominal Pain: Sensation of discomfort, distress, or agony in the abdominal region. [NIH] Aberrant: Wandering or deviating from the usual or normal course. [EU] Ablate: In surgery, is to remove. [NIH] Ablation: The removal of an organ by surgery. [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] Acetaldehyde: A colorless, flammable liquid used in the manufacture of acetic acid, perfumes, and flavors. It is also an intermediate in the metabolism of alcohol. It has a general narcotic action and also causes irritation of mucous membranes. Large doses may cause death from respiratory paralysis. [NIH] Acetylcholine: A neurotransmitter. Acetylcholine in vertebrates is the major transmitter at neuromuscular junctions, autonomic ganglia, parasympathetic effector junctions, a subset of sympathetic effector junctions, and at many sites in the central nervous system. It is generally not used as an administered drug because it is broken down very rapidly by cholinesterases, but it is useful in some ophthalmological applications. [NIH] Acne: A disorder of the skin marked by inflammation of oil glands and hair glands. [NIH] Acne Vulgaris: A chronic disorder of the pilosebaceous apparatus associated with an increase in sebum secretion. It is characterized by open comedones (blackheads), closed comedones (whiteheads), and pustular nodules. The cause is unknown, but heredity and age are predisposing factors. [NIH] Actin: Essential component of the cell skeleton. [NIH] Acyclovir: Functional analog of the nucleoside guanosine. It acts as an antimetabolite, especially in viruses. It is used as an antiviral agent, especially in herpes infections. [NIH] Acyl: Chemical signal used by bacteria to communicate. [NIH] Adaptability: Ability to develop some form of tolerance to conditions extremely different from those under which a living organism evolved. [NIH] Adaptation: 1. The adjustment of an organism to its environment, or the process by which it enhances such fitness. 2. The normal ability of the eye to adjust itself to variations in the intensity of light; the adjustment to such variations. 3. The decline in the frequency of firing of a neuron, particularly of a receptor, under conditions of constant stimulation. 4. In 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] Adenocarcinomas: A malignant tumor of the epithelial cells of a gland which typically
176 Doxycycline
metastasizes by way of the lymphatics. [NIH] Adenoma: A benign epithelial tumor with a glandular organization. [NIH] Adenosine: A nucleoside that is composed of adenine and d-ribose. Adenosine or adenosine derivatives play many important biological roles in addition to being components of DNA and RNA. Adenosine itself is a neurotransmitter. [NIH] 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] Adhesions: Pathological processes consisting of the union of the opposing surfaces of a wound. [NIH] Adipose Tissue: Connective tissue composed of fat cells lodged in the meshes of areolar tissue. [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] Adjuvant Therapy: Treatment given after the primary treatment to increase the chances of a cure. Adjuvant therapy may include chemotherapy, radiation therapy, or hormone therapy. [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] Adrenergic Agonists: Drugs that bind to and activate adrenergic receptors. [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] Aerosol: A solution of a drug which can be atomized into a fine mist for inhalation therapy. [EU]
Aetiology: Study of the causes of disease. [EU] Afferent: Concerned with the transmission of neural impulse toward the central part of the nervous system. [NIH] Affinity: 1. Inherent likeness or relationship. 2. A special attraction for a specific element, organ, or structure. 3. Chemical affinity; the force that binds atoms in molecules; the tendency of substances to combine by chemical reaction. 4. The strength of noncovalent chemical binding between two substances as measured by the dissociation constant of the complex. 5. In immunology, a thermodynamic expression of the strength of interaction between a single antigen-binding site and a single antigenic determinant (and thus of the stereochemical compatibility between them), most accurately applied to interactions among simple, uniform antigenic determinants such as haptens. Expressed as the association constant (K litres mole -1), which, owing to the heterogeneity of affinities in a population of antibody molecules of a given specificity, actually represents an average value (mean intrinsic association constant). 6. The reciprocal of the dissociation constant. [EU] Agar: A complex sulfated polymer of galactose units, extracted from Gelidium cartilagineum, Gracilaria confervoides, and related red algae. It is used as a gel in the preparation of solid culture media for microorganisms, as a bulk laxative, in making
Dictionary 177
emulsions, and as a supporting medium for immunodiffusion and immunoelectrophoresis. [NIH]
Age of Onset: The age or period of life at which a disease or the initial symptoms or manifestations of a disease appear in an individual. [NIH] Agonist: In anatomy, a prime mover. In pharmacology, a drug that has affinity for and stimulates physiologic activity at cell receptors normally stimulated by naturally occurring substances. [EU] Airway: A device for securing unobstructed passage of air into and out of the lungs during general anesthesia. [NIH] Aldehyde Dehydrogenase: An enzyme that oxidizes an aldehyde in the presence of NAD+ and water to an acid and NADH. EC 1.2.1.3. Before 1978, it was classified as EC 1.1.1.70. [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] Alkaline Phosphatase: An enzyme that catalyzes the conversion of an orthophosphoric monoester and water to an alcohol and orthophosphate. EC 3.1.3.1. [NIH] 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] Allergen: An antigenic substance capable of producing immediate-type hypersensitivity (allergy). [EU] Alpha 1-Antitrypsin: Plasma glycoprotein member of the serpin superfamily which inhibits trypsin, neutrophil elastase, and other proteolytic enzymes. Commonly referred to as alpha 1-proteinase inhibitor (A1PI), it exists in over 30 different biochemical variant forms known collectively as the PI (protease inhibitor) system. Hereditary A1PI deficiency is associated with pulmonary emphysema. [NIH] Alpha 1-Antitrypsin Deficiency: A disease caused by single gene defects. [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] Alpha-helix: One of the secondary element of protein. [NIH] Alprenolol: 1-((1-Methylethyl)amino)-3-(2-(2-propenyl)phenoxy)-2-propanol. Adrenergic beta-blocker used as an antihypertensive, anti-anginal, and anti-arrhythmic agent. [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] Alternative Splicing: A process whereby multiple protein isoforms are generated from a single gene. Alternative splicing involves the splicing together of nonconsecutive exons during the processing of some, but not all, transcripts of the gene. Thus a particular exon may be connected to any one of several alternative exons to form messenger RNA. The alternative forms produce proteins in which one part is common while the other part is different. [NIH] Alveolar Bone Loss: The resorption of bone in the supporting structures of the maxilla or
178 Doxycycline
mandible as a result of periodontal disease. [NIH] Alveolar Process: The thickest and spongiest part of the maxilla and mandible hollowed out into deep cavities for the teeth. [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] Amino Acid Sequence: The order of amino acids as they occur in a polypeptide chain. This is referred to as the primary structure of proteins. It is of fundamental importance in determining protein conformation. [NIH] Amino Acids: Organic compounds that generally contain an amino (-NH2) and a carboxyl (COOH) group. Twenty alpha-amino acids are the subunits which are polymerized to form proteins. [NIH] Amino Acids: Organic compounds that generally contain an amino (-NH2) and a carboxyl (COOH) group. Twenty alpha-amino acids are the subunits which are polymerized to form proteins. [NIH] 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] Ampulla: A sac-like enlargement of a canal or duct. [NIH] Amygdala: Almond-shaped group of basal nuclei anterior to the inferior horn of the lateral ventricle of the brain, within the temporal lobe. The amygdala is part of the limbic system. [NIH]
Amyloid: A general term for a variety of different proteins that accumulate as extracellular fibrils of 7-10 nm and have common structural features, including a beta-pleated sheet conformation and the ability to bind such dyes as Congo red and thioflavine (Kandel, Schwartz, and Jessel, Principles of Neural Science, 3rd ed). [NIH] Anaerobic: 1. Lacking molecular oxygen. 2. Growing, living, or occurring in the absence of molecular oxygen; pertaining to an anaerobe. [EU] Anaesthesia: Loss of feeling or sensation. Although the term is used for loss of tactile sensibility, or of any of the other senses, it is applied especially to loss of the sensation of pain, as it is induced to permit performance of surgery or other painful procedures. [EU] 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]
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Anatomical: Pertaining to anatomy, or to the structure of the organism. [EU] Anemia: A reduction in the number of circulating erythrocytes or in the quantity of hemoglobin. [NIH] Anesthesia: A state characterized by loss of feeling or sensation. This depression of nerve function is usually the result of pharmacologic action and is induced to allow performance of surgery or other painful procedures. [NIH] Aneuploidy: The chromosomal constitution of cells which deviate from the normal by the addition or subtraction of chromosomes or chromosome pairs. In a normally diploid cell the loss of a chromosome pair is termed nullisomy (symbol: 2N-2), the loss of a single chromosome is monosomy (symbol: 2N-1), the addition of a chromosome pair is tetrasomy (symbol: 2N+2), the addition of a single chromosome is trisomy (symbol: 2N+1). [NIH] 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 from surrounding tissue to a solid tumor. This is caused by the release of chemicals by the tumor. [NIH] Angiopathy: Disease of the blood vessels (arteries, veins, and capillaries) that occurs when someone has diabetes for a long time. There are two types of angiopathy: macroangiopathy and microangiopathy. In macroangiopathy, fat and blood clots build up in the large blood vessels, stick to the vessel walls, and block the flow of blood. In microangiopathy, the walls of the smaller blood vessels become so thick and weak that they bleed, leak protein, and slow the flow of blood through the body. Then the cells, for example, the ones in the center of the eye, do not get enough blood and may be damaged. [NIH] Animal model: An animal with a disease either the same as or like a disease in humans. Animal models are used to study the development and progression of diseases and to test new treatments before they are given to humans. Animals with transplanted human cancers or other tissues are called xenograft models. [NIH] Anions: Negatively charged atoms, radicals or groups of atoms which travel to the anode or positive pole during electrolysis. [NIH] Anisotropy: A physical property showing different values in relation to the direction in or along which the measurement is made. The physical property may be with regard to thermal or electric conductivity or light refraction. In crystallography, it describes crystals whose index of refraction varies with the direction of the incident light. It is also called acolotropy and colotropy. The opposite of anisotropy is isotropy wherein the same values characterize the object when measured along axes in all directions. [NIH] Annealing: The spontaneous alignment of two single DNA strands to form a double helix. [NIH]
Antagonism: Interference with, or inhibition of, the growth of a living organism by another living organism, due either to creation of unfavorable conditions (e. g. exhaustion of food supplies) or to production of a specific antibiotic substance (e. g. penicillin). [NIH] Anthrax: An acute bacterial infection caused by ingestion of bacillus organisms. Carnivores may become infected from ingestion of infected carcasses. It is transmitted to humans by
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contact with infected animals or contaminated animal products. The most common form in humans is cutaneous anthrax. [NIH] Antibacterial: A substance that destroys bacteria or suppresses their growth or reproduction. [EU] Antibiotic: A drug used to treat infections caused by bacteria and other microorganisms. [NIH]
Antibodies: Immunoglobulin molecules having a specific amino acid sequence by virtue of which they interact only with the antigen that induced their synthesis in cells of the lymphoid series (especially plasma cells), or with an antigen closely related to it. [NIH] Antibody: A type of protein made by certain white blood cells in response to a foreign substance (antigen). Each antibody can bind to only a specific antigen. The purpose of this binding is to help destroy the antigen. Antibodies can work in several ways, depending on the nature of the antigen. Some antibodies destroy antigens directly. Others make it easier for white blood cells to destroy the antigen. [NIH] Anticoagulant: A drug that helps prevent blood clots from forming. Also called a blood thinner. [NIH] 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] 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] 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]
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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] Aponeurosis: Tendinous expansion consisting of a fibrous or membranous sheath which serves as a fascia to enclose or bind a group of muscles. [NIH] Apoptosis: One of the two mechanisms by which cell death occurs (the other being the pathological process of necrosis). Apoptosis is the mechanism responsible for the physiological deletion of cells and appears to be intrinsically programmed. It is characterized by distinctive morphologic changes in the nucleus and cytoplasm, chromatin cleavage at regularly spaced sites, and the endonucleolytic cleavage of genomic DNA (DNA fragmentation) at internucleosomal sites. This mode of cell death serves as a balance to mitosis in regulating the size of animal tissues and in mediating pathologic processes associated with tumor growth. [NIH] Aqueous: Having to do with water. [NIH] Arachidonate 12-Lipoxygenase: An enzyme that catalyzes the oxidation of arachidonic acid to yield 12-hydroperoxyarachidonate (12-HPETE) which is itself rapidly converted by a peroxidase to 12-hydroxy-5,8,10,14-eicosatetraenoate (12-HETE). The 12-hydroperoxides are preferentially formed in platelets. EC 1.13.11.31. [NIH] Arachidonate 15-Lipoxygenase: An enzyme that catalyzes the oxidation of arachidonic acid to yield 15-hydroperoxyarachidonate (15-HPETE) which is rapidly converted to 15-hydroxy5,8,11,13-eicosatetraenoate (15-HETE). The 15-hydroperoxides are preferentially formed in neutrophils and lymphocytes. EC 1.13.11.33. [NIH] Arachidonate Lipoxygenases: Enzymes catalyzing the oxidation of arachidonic acid to hydroperoxyarachidonates (HPETES). These products are then rapidly converted by a peroxidase to hydroxyeicosatetraenoic acids (HETES). The positional specificity of the enzyme reaction varies from tissue to tissue. The final lipoxygenase pathway leads to the leukotrienes. EC 1.13.11.- . [NIH] Arginine: An essential amino acid that is physiologically active in the L-form. [NIH] Arterial: Pertaining to an artery or to the arteries. [EU] Arteries: The vessels carrying blood away from the heart. [NIH] Arterioles: The smallest divisions of the arteries located between the muscular arteries and the capillaries. [NIH] Articular: Of or pertaining to a joint. [EU] Asbestos: Fibrous incombustible mineral composed of magnesium and calcium silicates with or without other elements. It is relatively inert chemically and used in thermal insulation and fireproofing. Inhalation of dust causes asbestosis and later lung and gastrointestinal neoplasms. [NIH] Ascites: Accumulation or retention of free fluid within the peritoneal cavity. [NIH] Ascorbic Acid: A six carbon compound related to glucose. It is found naturally in citrus fruits and many vegetables. Ascorbic acid is an essential nutrient in human diets, and necessary to maintain connective tissue and bone. Its biologically active form, vitamin C, functions as a reducing agent and coenzyme in several metabolic pathways. Vitamin C is considered an antioxidant. [NIH] Aseptic: Free from infection or septic material; sterile. [EU] Aspartate: A synthetic amino acid. [NIH] Assay: Determination of the amount of a particular constituent of a mixture, or of the
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biological or pharmacological potency of a drug. [EU] Astrocytes: The largest and most numerous neuroglial cells in the brain and spinal cord. Astrocytes (from "star" cells) are irregularly shaped with many long processes, including those with "end feet" which form the glial (limiting) membrane and directly and indirectly contribute to the blood brain barrier. They regulate the extracellular ionic and chemical environment, and "reactive astrocytes" (along with microglia) respond to injury. Astrocytes have high- affinity transmitter uptake systems, voltage-dependent and transmitter-gated ion channels, and can release transmitter, but their role in signaling (as in many other functions) is not well understood. [NIH] Asymptomatic: Having no signs or symptoms of disease. [NIH] Atopic: Pertaining to an atopen or to atopy; allergic. [EU] 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] 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] 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] Bacteremia: The presence of viable bacteria circulating in the blood. Fever, chills, tachycardia, and tachypnea are common acute manifestations of bacteremia. The majority of cases are seen in already hospitalized patients, most of whom have underlying diseases or procedures which render their bloodstreams susceptible to invasion. [NIH] Bacteria: Unicellular prokaryotic microorganisms which generally possess rigid cell walls, multiply by cell division, and exhibit three principal forms: round or coccal, rodlike or bacillary, and spiral or spirochetal. [NIH] Bacterial Infections: Infections by bacteria, general or unspecified. [NIH]
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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] 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] Basal Ganglia: Large subcortical nuclear masses derived from the telencephalon and located in the basal regions of the cerebral hemispheres. [NIH] Base: In chemistry, the nonacid part of a salt; a substance that combines with acids to form salts; a substance that dissociates to give hydroxide ions in aqueous solutions; a substance whose molecule or ion can combine with a proton (hydrogen ion); a substance capable of donating a pair of electrons (to an acid) for the formation of a coordinate covalent bond. [EU] Basement Membrane: Ubiquitous supportive tissue adjacent to epithelium and around smooth and striated muscle cells. This tissue contains intrinsic macromolecular components such as collagen, laminin, and sulfated proteoglycans. As seen by light microscopy one of its subdivisions is the basal (basement) lamina. [NIH] Basophils: Granular leukocytes characterized by a relatively pale-staining, lobate nucleus 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]
Beta-Galactosidase: A group of enzymes that catalyzes the hydrolysis of terminal, nonreducing beta-D-galactose residues in beta-galactosides. Deficiency of beta-Galactosidase A1 may cause gangliodisosis GM1. EC 3.2.1.23. [NIH] Beta-pleated: Particular three-dimensional pattern of amyloidoses. [NIH] Beta-Thromboglobulin: A platelet-specific protein which is released when platelets aggregate. Elevated plasma levels have been reported after deep venous thrombosis, preeclampsia, myocardial infarction with mural thrombosis, and myeloproliferative disorders. Measurement of beta-thromboglobulin in biological fluids by radioimmunoassay is used for the diagnosis and assessment of progress of thromboembolic disorders. [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 Ducts: Tubes that carry bile from the liver to the gallbladder for storage and to the small intestine for use in digestion. [NIH] Binding Sites: The reactive parts of a macromolecule that directly participate in its specific combination with another molecule. [NIH] Bioassay: Determination of the relative effective strength of a substance (as a vitamin, hormone, or drug) by comparing its effect on a test organism with that of a standard preparation. [NIH] Biochemical: Relating to biochemistry; characterized by, produced by, or involving chemical reactions in living organisms. [EU]
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Biofilms: Films of bacteria or other microbial organisms, usually embedded in extracellular polymers such as implanted medical devices, which adhere to surfaces submerged in, or subjected to, aquatic environments (From Singleton & Sainsbury, Dictionary of Microbiology and Molecular Biology, 2d ed). Biofilms consist of multilayers of microbial cells glued together to form microbial communities which are highly resistant to both phagocytes and antibiotics. [NIH] Biological response modifier: BRM. A substance that stimulates the body's response to infection and disease. [NIH] Biological therapy: Treatment to stimulate or restore the ability of the immune system to fight infection and disease. Also used to lessen side effects that may be caused by some cancer treatments. Also known as immunotherapy, biotherapy, or biological response modifier (BRM) therapy. [NIH] Biopsy: Removal and pathologic examination of specimens in the form of small pieces of tissue from the living body. [NIH] Biopsy specimen: Tissue removed from the body and examined under a microscope to determine whether disease is present. [NIH] Biosynthesis: The building up of a chemical compound in the physiologic processes of a living organism. [EU] Biotechnology: Body of knowledge related to the use of organisms, cells or cell-derived constituents for the purpose of developing products which are technically, scientifically and clinically useful. Alteration of biologic function at the molecular level (i.e., genetic engineering) is a central focus; laboratory methods used include transfection and cloning technologies, sequence and structure analysis algorithms, computer databases, and gene and protein structure function analysis and prediction. [NIH] Bladder: The organ that stores urine. [NIH] Bleomycin: A complex of related glycopeptide antibiotics from Streptomyces verticillus consisting of bleomycin A2 and B2. It inhibits DNA metabolism and is used as an antineoplastic, especially for solid tumors. [NIH] 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 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 Volume: Volume of circulating blood. It is the sum of the plasma volume and erythrocyte volume. [NIH] Blood-Brain Barrier: Specialized non-fenestrated tightly-joined endothelial cells (tight junctions) that form a transport barrier for certain substances between the cerebral capillaries and the brain tissue. [NIH] Blot: To transfer DNA, RNA, or proteins to an immobilizing matrix such as nitrocellulose. [NIH]
Body Fluids: Liquid components of living organisms. [NIH] Body Mass Index: One of the anthropometric measures of body mass; it has the highest
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correlation with skinfold thickness or body density. [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 Cells: Cells contained in the bone marrow including fat cells, stromal cells, megakaryocytes, and the immediate precursors of most blood 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] 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 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] 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] Bronchiectasis: Persistent abnormal dilatation of the bronchi. [NIH] Bronchitis: Inflammation (swelling and reddening) of the bronchi. [NIH] Bronchoalveolar Lavage: Washing out of the lungs with saline or mucolytic agents for diagnostic or therapeutic purposes. It is very useful in the diagnosis of diffuse pulmonary infiltrates in immunosuppressed patients. [NIH] Bronchoconstriction: Diminution of the caliber of a bronchus physiologically or as a result of pharmacological intervention. [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
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treated for respiratory distress syndrome with mechanical ventilation and elevated concentration of inspired oxygen. [NIH] Bronchus: A large air passage that leads from the trachea (windpipe) to the lung. [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] 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] Callus: A callosity or hard, thick skin; the bone-like reparative substance that is formed round the edges and fragments of broken bone. [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]
Capillary: Any one of the minute vessels that connect the arterioles and venules, forming a network in nearly all parts of the body. Their walls act as semipermeable membranes for the interchange of various substances, including fluids, between the blood and tissue fluid; called also vas capillare. [EU] Caprolactam: Cyclic amide of caproic acid used in manufacture of synthetic fibers of the polyamide type. Can cause local irritation. [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] Carboxy: Cannabinoid. [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]
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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] Cardioselective: Having greater activity on heart tissue than on other tissue. [EU] Cardiovascular: Having to do with the heart and blood vessels. [NIH] Cardiovascular disease: Any abnormal condition characterized by dysfunction of the heart and blood vessels. CVD includes atherosclerosis (especially coronary heart disease, which can lead to heart attacks), cerebrovascular disease (e.g., stroke), and hypertension (high blood pressure). [NIH] Carotene: The general name for a group of pigments found in green, yellow, and leafy vegetables, and yellow fruits. The pigments are fat-soluble, unsaturated aliphatic hydrocarbons functioning as provitamins and are converted to vitamin A through enzymatic processes in the intestinal wall. [NIH] Case report: A detailed report of the diagnosis, treatment, and follow-up of an individual patient. Case reports also contain some demographic information about the patient (for example, age, gender, ethnic origin). [NIH] Caspase: Enzyme released by the cell at a crucial stage in apoptosis in order to shred all cellular proteins. [NIH] Catecholamine: A group of chemical substances manufactured by the adrenal medulla and secreted during physiological stress. [NIH] Cathepsins: A group of lysosomal proteinases or endopeptidases found in aqueous extracts of a variety of animal tissue. They function optimally within an acidic pH range. [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] Caudate Nucleus: Elongated gray mass of the neostriatum located adjacent to the lateral ventricle of the brain. [NIH] Causal: Pertaining to a cause; directed against a cause. [EU] Cause of Death: Factors which produce cessation of all vital bodily functions. They can be analyzed from an epidemiologic viewpoint. [NIH] Cefaclor: Semisynthetic, broad-spectrum antibiotic derivative of cephalexin. [NIH] Cefoxitin: Semisynthetic cephamycin antibiotic resistant to beta-lactamase. [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] Cefuroxime: Broad-spectrum cephalosporin antibiotic resistant to beta-lactamase. It has been proposed for infections with gram-negative and gram-positive organisms, gonorrhea, and haemophilus. [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 Cycle: The complex series of phenomena, occurring between the end of one cell
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division and the end of the next, by which cellular material is divided between daughter cells. [NIH] Cell Death: The termination of the cell's ability to carry out vital functions such as metabolism, growth, reproduction, responsiveness, and adaptability. [NIH] Cell Differentiation: Progressive restriction of the developmental potential and increasing specialization of function which takes place during the development of the embryo and leads to the formation of specialized cells, tissues, and organs. [NIH] Cell Division: The fission of a cell. [NIH] Cell membrane: Cell membrane = plasma membrane. The structure enveloping a cell, enclosing the cytoplasm, and forming a selective permeability barrier; it consists of lipids, proteins, and some carbohydrates, the lipids thought to form a bilayer in which integral proteins are embedded to varying degrees. [EU] Cell motility: The ability of a cell to move. [NIH] Cell proliferation: An increase in the number of cells as a result of cell growth and cell division. [NIH] Cell Respiration: The metabolic process of all living cells (animal and plant) in which oxygen is used to provide a source of energy for the cell. [NIH] Cell Size: The physical dimensions of a cell. It refers mainly to changes in dimensions correlated with physiological or pathological changes in cells. [NIH] Cell Survival: The span of viability of a cell characterized by the capacity to perform certain functions such as metabolism, growth, reproduction, some form of responsiveness, and adaptability. [NIH] Cell Transplantation: Transference of cells within an individual, between individuals of the same species, or between individuals of different species. [NIH] Cellulose: A polysaccharide with glucose units linked as in cellobiose. It is the chief constituent of plant fibers, cotton being the purest natural form of the substance. As a raw material, it forms the basis for many derivatives used in chromatography, ion exchange materials, explosives manufacturing, and pharmaceutical preparations. [NIH] Central Nervous System: The main information-processing organs of the nervous system, consisting of the brain, spinal cord, and meninges. [NIH] Central Nervous System Infections: Pathogenic infections of the brain, spinal cord, and meninges. DNA virus infections; RNA virus infections; bacterial infections; mycoplasma infections; Spirochaetales infections; fungal infections; protozoan infections; helminthiasis; and prion diseases may involve the central nervous system as a primary or secondary process. [NIH] Centrifugation: A method of separating organelles or large molecules that relies upon differential sedimentation through a preformed density gradient under the influence of a gravitational field generated in a centrifuge. [NIH] Centrosome: The cell center, consisting of a pair of centrioles surrounded by a cloud of amorphous material called the pericentriolar region. During interphase, the centrosome nucleates microtubule outgrowth. The centrosome duplicates and, during mitosis, separates to form the two poles of the mitotic spindle (mitotic spindle apparatus). [NIH] Cephalexin: A semisynthetic cephalosporin antibiotic with antimicrobial activity similar to that of cephaloridine or cephalothin, but somewhat less potent. It is effective against both gram-positive and gram-negative organisms. [NIH] Cerebral: Of or pertaining of the cerebrum or the brain. [EU]
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Cerebrospinal: Pertaining to the brain and spinal cord. [EU] Cerebrospinal fluid: CSF. The fluid flowing around the brain and spinal cord. Cerebrospinal fluid is produced in the ventricles in the brain. [NIH] Cerebrovascular: Pertaining to the blood vessels of the cerebrum, or brain. [EU] Cerebrum: The largest part of the brain. It is divided into two hemispheres, or halves, called the cerebral hemispheres. The cerebrum controls muscle functions of the body and also controls speech, emotions, reading, writing, and learning. [NIH] Cervical: Relating to the neck, or to the neck of any organ or structure. Cervical lymph nodes are located in the neck; cervical cancer refers to cancer of the uterine cervix, which is the lower, narrow end (the "neck") of the uterus. [NIH] Cervix: The lower, narrow end of the uterus that forms a canal between the uterus and vagina. [NIH] 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] 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] Chemotherapy: Treatment with anticancer drugs. [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] Chlortetracycline: An antibiotic substance isolated from the substrate of Streptomyces aureofaciens and used as an antibacterial and antiprotozoal agent. [NIH] Cholangiography: Radiographic examination of the bile ducts. [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] Cholesterol: The principal sterol of all higher animals, distributed in body tissues, especially the brain and spinal cord, and in animal fats and oils. [NIH] Choline: A basic constituent of lecithin that is found in many plants and animal organs. It is important as a precursor of acetylcholine, as a methyl donor in various metabolic processes, and in lipid metabolism. [NIH] Cholinergic: Resembling acetylcholine in pharmacological action; stimulated by or releasing acetylcholine or a related compound. [EU] 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]
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Choroid: The thin, highly vascular membrane covering most of the posterior of the eye between the retina and sclera. [NIH] Chromatin: The material of chromosomes. It is a complex of DNA, histones, and nonhistone proteins (chromosomal proteins, non-histone) found within the nucleus of a cell. [NIH] Chromosomal: Pertaining to chromosomes. [EU] Chromosome: Part of a cell that contains genetic information. Except for sperm and eggs, all human cells contain 46 chromosomes. [NIH] 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] 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] 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] 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]
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Clinical trial: A research study that tests how well new medical treatments or other interventions work in people. Each study is designed to test new methods of screening, prevention, diagnosis, or treatment of a disease. [NIH] Clone: The term "clone" has acquired a new meaning. It is applied specifically to the bits of inserted foreign DNA in the hybrid molecules of the population. Each inserted segment originally resided in the DNA of a complex genome amid millions of other DNA segment. [NIH]
Cloning: The production of a number of genetically identical individuals; in genetic engineering, a process for the efficient replication of a great number of identical DNA molecules. [NIH] Cloxacillin: A semi-synthetic antibiotic that is a chlorinated derivative of oxacillin. [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] Cochlea: The part of the internal ear that is concerned with hearing. It forms the anterior part of the labyrinth, is conical, and is placed almost horizontally anterior to the vestibule. [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] 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] 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] Combinatorial: A cut-and-paste process that churns out thousands of potentially valuable compounds at once. [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.
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Fragments resulting from proteolytic cleavage of complement proteins are designated with lower-case letter suffixes, e.g., C3a. Inactivated fragments may be designated with the suffix 'i', e.g. C3bi. Activated components or complexes with biological activity are designated by a bar over the symbol e.g. C1 or C4b,2a. The classic pathway is activated by the binding of C1 to classic pathway activators, primarily antigen-antibody complexes containing IgM, IgG1, IgG3; C1q binds to a single IgM molecule or two adjacent IgG molecules. The alternative pathway can be activated by IgA immune complexes and also by nonimmunologic materials including bacterial endotoxins, microbial polysaccharides, and cell walls. Activation of the classic pathway triggers an enzymatic cascade involving C1, C4, C2 and C3; activation of the alternative pathway triggers a cascade involving C3 and factors B, D and P. Both result in the cleavage of C5 and the formation of the membrane attack complex. Complement activation also results in the formation of many biologically active complement fragments that act as anaphylatoxins, opsonins, or chemotactic factors. [EU] Complementary and alternative medicine: CAM. Forms of treatment that are used in addition to (complementary) or instead of (alternative) standard treatments. These practices are not considered standard medical approaches. CAM includes dietary supplements, megadose vitamins, herbal preparations, special teas, massage therapy, magnet therapy, spiritual healing, and meditation. [NIH] Complementary medicine: Practices not generally recognized by the medical community as standard or conventional medical approaches and used to enhance or complement the standard treatments. Complementary medicine includes the taking of dietary supplements, megadose vitamins, and herbal preparations; the drinking of special teas; and practices such as massage therapy, magnet therapy, spiritual healing, and meditation. [NIH] Computational Biology: A field of biology concerned with the development of techniques for the collection and manipulation of biological data, and the use of such data to make biological discoveries or predictions. This field encompasses all computational methods and theories applicable to molecular biology and areas of computer-based techniques for solving biological problems including manipulation of models and datasets. [NIH] Conception: The onset of pregnancy, marked by implantation of the blastocyst; the formation of a viable zygote. [EU] Condoms: A sheath that is worn over the penis during sexual behavior in order to prevent pregnancy or spread of sexually transmitted disease. [NIH] 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] Congestion: Excessive or abnormal accumulation of blood in a part. [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]
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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] Continuous infusion: The administration of a fluid into a blood vessel, usually over a prolonged period of time. [NIH] 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] Contractility: Capacity for becoming short in response to a suitable stimulus. [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] Control group: In a clinical trial, the group that does not receive the new treatment being studied. This group is compared to the group that receives the new treatment, to see if the new treatment works. [NIH] Controlled 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]
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 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] 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 heart disease: A type of heart disease caused by narrowing of the coronary
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arteries that feed the heart, which needs a constant supply of oxygen and nutrients carried by the blood in the coronary arteries. When the coronary arteries become narrowed or clogged by fat and cholesterol deposits and cannot supply enough blood to the heart, CHD results. [NIH] Coronary Thrombosis: Presence of a thrombus in a coronary artery, often causing a myocardial infarction. [NIH] 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] Corticosteroids: Hormones that have antitumor activity in lymphomas and lymphoid leukemias; in addition, corticosteroids (steroids) may be used for hormone replacement and for the management of some of the complications of cancer and its treatment. [NIH] Coumarin: A fluorescent dye. [NIH] Cranial: Pertaining to the cranium, or to the anterior (in animals) or superior (in humans) end of the body. [EU] Craniocerebral Trauma: Traumatic injuries involving the cranium and intracranial structures (i.e., brain; cranial nerves; meninges; and other structures). Injuries may be classified by whether or not the skull is penetrated (i.e., penetrating vs. nonpenetrating) or whether there is an associated hemorrhage. [NIH] Creatine: An amino acid that occurs in vertebrate tissues and in urine. In muscle tissue, creatine generally occurs as phosphocreatine. Creatine is excreted as creatinine in the urine. [NIH]
Creatine Kinase: A transferase that catalyzes formation of phosphocreatine from ATP + creatine. The reaction stores ATP energy as phosphocreatine. Three cytoplasmic isoenzymes have been identified in human tissues: MM from skeletal muscle, MB from myocardial tissue, and BB from nervous tissue as well as a mitochondrial isoenzyme. Macro-creatine kinase refers to creatine kinase complexed with other serum proteins. EC 2.7.3.2. [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] Cryptosporidiosis: Parasitic intestinal infection with severe diarrhea caused by a protozoan, Cryptosporidium. It occurs in both animals and humans. [NIH] Cultured cells: Animal or human cells that are grown in the laboratory. [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]
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]
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Cysteine: A thiol-containing non-essential amino acid that is oxidized to form cystine. [NIH] Cystine: A covalently linked dimeric nonessential amino acid formed by the oxidation of cysteine. Two molecules of cysteine are joined together by a disulfide bridge to form cystine. [NIH]
Cystitis: Inflammation of the urinary bladder. [EU] Cytokine: Small but highly potent protein that modulates the activity of many cell types, including T and B cells. [NIH] Cytoplasm: The protoplasm of a cell exclusive of that of the nucleus; it consists of a continuous aqueous solution (cytosol) and the organelles and inclusions suspended in it (phaneroplasm), and is the site of most of the chemical activities of the cell. [EU] Cytoskeleton: The network of filaments, tubules, and interconnecting filamentous bridges which give shape, structure, and organization to the cytoplasm. [NIH] Cytotoxic: Cell-killing. [NIH] 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] Decubitus: An act of lying down; also the position assumed in lying down. [EU] Decubitus Ulcer: An ulceration caused by prolonged pressure in patients permitted to lie too still for a long period of time. The bony prominences of the body are the most frequently affected sites. The ulcer is caused by ischemia of the underlying structures of the skin, fat, and muscles as a result of the sustained and constant pressure. [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 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]
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Dendritic cell: A special type of antigen-presenting cell (APC) that activates T lymphocytes. [NIH]
Density: The logarithm to the base 10 of the opacity of an exposed and processed film. [NIH] Dentate Gyrus: Gray matter situated above the gyrus hippocampi. It is composed of three layers. The molecular layer is continuous with the hippocampus in the hippocampal fissure. The granular layer consists of closely arranged spherical or oval neurons, called granule cells, whose axons pass through the polymorphic layer ending on the dendrites of pyramidal cells in the hippocampus. [NIH] Dentin Permeability: The property of dentin that permits passage of light, heat, cold, and chemical substances. It does not include penetration by microorganisms. [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] Depressive Disorder: An affective disorder manifested by either a dysphoric mood or loss of interest or pleasure in usual activities. The mood disturbance is prominent and relatively persistent. [NIH] Dermal: Pertaining to or coming from the skin. [NIH] DES: Diethylstilbestrol. A synthetic hormone that was prescribed from the early 1940s until 1971 to help women with complications of pregnancy. DES has been linked to an increased risk of clear cell carcinoma of the vagina in daughters of women who used DES. DES may also increase the risk of breast cancer in women who used DES. [NIH] Diabetes Mellitus: A heterogeneous group of disorders that share glucose intolerance in common. [NIH] Diagnostic procedure: A method used to identify a disease. [NIH] Diaphragm: The musculofibrous partition that separates the thoracic cavity from the abdominal cavity. Contraction of the diaphragm increases the volume of the thoracic cavity aiding inspiration. [NIH] Diarrhea: Passage of excessively liquid or excessively frequent stools. [NIH] 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] 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] Dihydrotestosterone: Anabolic agent. [NIH] Dilatation: The act of dilating. [NIH] Dimerization: The process by which two molecules of the same chemical composition form a condensation product or polymer. [NIH] Diploid: Having two sets of chromosomes. [NIH] Direct: 1. Straight; in a straight line. 2. Performed immediately and without the intervention
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of subsidiary means. [EU] Disease Progression: The worsening of a disease over time. This concept is most often used for chronic and incurable diseases where the stage of the disease is an important determinant of therapy and prognosis. [NIH] Disinfectant: An agent that disinfects; applied particularly to agents used on inanimate objects. [EU] 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] Disulfiram: A carbamate derivative used as an alcohol deterrent. It is a relatively nontoxic substance when administered alone, but markedly alters the intermediary metabolism of alcohol. When alcohol is ingested after administration of disulfiram, blood acetaldehyde concentrations are increased, followed by flushing, systemic vasodilation, respiratory difficulties, nausea, hypotension, and other symptoms (acetaldehyde syndrome). It acts by inhibiting aldehyde dehydrogenase. [NIH] Disulphides: A covalent bridge formed by the oxidation of two cysteine residues to a cystine residue. The-S-S-bond is very strong and its presence confers additional stability. [NIH]
Dithiothreitol: A reagent commonly used in biochemical studies as a protective agent to prevent the oxidation of SH (thiol) groups and for reducing disulphides to dithiols. [NIH] Diuresis: Increased excretion of urine. [EU] Dizziness: An imprecise term which may refer to a sense of spatial disorientation, motion of the environment, or lightheadedness. [NIH] Dopamine: An endogenous catecholamine and prominent neurotransmitter in several systems of the brain. In the synthesis of catecholamines from tyrosine, it is the immediate precursor to norepinephrine and epinephrine. Dopamine is a major transmitter in the extrapyramidal system of the brain, and important in regulating movement. A family of dopaminergic receptor subtypes mediate its action. Dopamine is used pharmacologically for its direct (beta adrenergic agonist) and indirect (adrenergic releasing) sympathomimetic effects including its actions as an inotropic agent and as a renal vasodilator. [NIH] Dorsal: 1. Pertaining to the back or to any dorsum. 2. Denoting a position more toward the back surface than some other object of reference; same as posterior in human anatomy; superior in the anatomy of quadrupeds. [EU] Dorsum: A plate of bone which forms the posterior boundary of the sella turcica. [NIH] 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]
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Dose-dependent: Refers to the effects of treatment with a drug. If the effects change when the dose of the drug is changed, the effects are said to be dose dependent. [NIH] Double-blinded: A clinical trial in which neither the medical staff nor the person knows which of several possible therapies the person is receiving. [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 Interactions: The action of a drug that may affect the activity, metabolism, or toxicity of another drug. [NIH] Drug Tolerance: Progressive diminution of the susceptibility of a human or animal to the effects of a drug, resulting from its continued administration. It should be differentiated from drug resistance wherein an organism, disease, or tissue fails to respond to the intended effectiveness of a chemical or drug. It should also be differentiated from maximum tolerated dose and no-observed-adverse-effect level. [NIH] Duct: A tube through which body fluids pass. [NIH] 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] Ectopic: Pertaining to or characterized by ectopia. [EU] Ectopic Pregnancy: The pregnancy occurring elsewhere than in the cavity of the uterus. [NIH]
Edema: Excessive amount of watery fluid accumulated in the intercellular spaces, most commonly present in subcutaneous tissue. [NIH] Effector: It is often an enzyme that converts an inactive precursor molecule into an active second messenger. [NIH] Effector cell: A cell that performs a specific function in response to a stimulus; usually used to describe cells in the immune system. [NIH] Efficacy: The extent to which a specific intervention, procedure, regimen, or service produces a beneficial result under ideal conditions. Ideally, the determination of efficacy is based on the results of a randomized control trial. [NIH] Elastin: The protein that gives flexibility to tissues. [NIH] Elective: Subject to the choice or decision of the patient or physician; applied to procedures that are advantageous to the patient but not urgent. [EU] Electrocoagulation: Electrosurgical procedures used to treat hemorrhage (e.g., bleeding ulcers) and to ablate tumors, mucosal lesions, and refractory arrhythmias. [NIH] Electrolysis: Destruction by passage of a galvanic electric current, as in disintegration of a chemical compound in solution. [NIH] Electrolyte: A substance that dissociates into ions when fused or in solution, and thus becomes capable of conducting electricity; an ionic solute. [EU]
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Electron Spin Resonance Spectroscopy: A technique applicable to the wide variety of substances which exhibit paramagnetism because of the magnetic moments of unpaired electrons. The spectra are useful for detection and identification, for determination of electron structure, for study of interactions between molecules, and for measurement of nuclear spins and moments. (From McGraw-Hill Encyclopedia of Science and Technology, 7th edition) Electron nuclear double resonance (ENDOR) spectroscopy is a variant of the technique which can give enhanced resolution. Electron spin resonance analysis can now be used in vivo, including imaging applications such as magnetic resonance imaging. [NIH] Electrons: Stable elementary particles having the smallest known negative charge, present in all elements; also called negatrons. Positively charged electrons are called positrons. The numbers, energies and arrangement of electrons around atomic nuclei determine the chemical identities of elements. Beams of electrons are called cathode rays or beta rays, the latter being a high-energy biproduct of nuclear decay. [NIH] Electrophoresis: An electrochemical process in which macromolecules or colloidal particles with a net electric charge migrate in a solution under the influence of an electric current. [NIH]
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] 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] Emepronium: A muscarinic antagonist used mainly in the treatment of urinary syndromes. It is incompletely absorbed from the gastrointestinal tract and does not cross the blood-brain barrier. [NIH] Emollient: Softening or soothing; called also malactic. [EU] Emphysema: A pathological accumulation of air in tissues or organs. [NIH] Enamel: A very hard whitish substance which covers the dentine of the anatomical crown of a tooth. [NIH] Encapsulated: Confined to a specific, localized area and surrounded by a thin layer of tissue. [NIH]
Encephalopathy: A disorder of the brain that can be caused by disease, injury, drugs, or chemicals. [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]
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Endocardium: The innermost layer of the heart, comprised of endothelial cells. [NIH] Endometrial: Having to do with the endometrium (the layer of tissue that lines the uterus). [NIH]
Endometrium: The layer of tissue that lines the uterus. [NIH] Endopeptidases: A subclass of peptide hydrolases. They are classified primarily by their catalytic mechanism. Specificity is used only for identification of individual enzymes. They comprise the serine endopeptidases, EC 3.4.21; cysteine endopeptidases, EC 3.4.22; aspartic endopeptidases, EC 3.4.23, metalloendopeptidases, EC 3.4.24; and a group of enzymes yet to be assigned to any of the above sub-classes, EC 3.4.99. EC 3.4.-. [NIH] Endoscope: A thin, lighted tube used to look at tissues inside the body. [NIH] Endoscopic: A technique where a lateral-view endoscope is passed orally to the duodenum for visualization of the ampulla of Vater. [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-derived: Small molecule that diffuses to the adjacent muscle layer and relaxes it. [NIH] Endotoxin: Toxin from cell walls of bacteria. [NIH] End-stage renal: Total chronic kidney failure. When the kidneys fail, the body retains fluid and harmful wastes build up. A person with ESRD needs treatment to replace the work of the failed kidneys. [NIH] Enhancer: Transcriptional element in the virus genome. [NIH] Entorhinal Cortex: Cortex where the signals are combined with those from other sensory systems. [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-Linked Immunosorbent Assay: An immunoassay utilizing an antibody labeled with an enzyme marker such as horseradish peroxidase. While either the enzyme or the antibody is bound to an immunosorbent substrate, they both retain their biologic activity; the change in enzyme activity as a result of the enzyme-antibody-antigen reaction is proportional to the concentration of the antigen and can be measured spectrophotometrically or with the naked eye. Many variations of the method have been developed. [NIH] Eosinophilic: A condition found primarily in grinding workers caused by a reaction of the pulmonary tissue, in particular the eosinophilic cells, to dust that has entered the lung. [NIH] Eosinophils: Granular leukocytes with a nucleus that usually has two lobes connected by a slender thread of chromatin, and cytoplasm containing coarse, round granules that are
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uniform in size and stainable by eosin. [NIH] Epidemic: Occurring suddenly in numbers clearly in excess of normal expectancy; said especially of infectious diseases but applied also to any disease, injury, or other healthrelated event occurring in such outbreaks. [EU] Epidemiological: Relating to, or involving epidemiology. [EU] Epidermal: Pertaining to or resembling epidermis. Called also epidermic or epidermoid. [EU] Epidermal Growth Factor: A 6 kD polypeptide growth factor initially discovered in mouse submaxillary glands. Human epidermal growth factor was originally isolated from urine based on its ability to inhibit gastric secretion and called urogastrone. epidermal growth factor exerts a wide variety of biological effects including the promotion of proliferation and differentiation of mesenchymal and epithelial cells. [NIH] Epidermis: Nonvascular layer of the skin. It is made up, from within outward, of five layers: 1) basal layer (stratum basale epidermidis); 2) spinous layer (stratum spinosum epidermidis); 3) granular layer (stratum granulosum epidermidis); 4) clear layer (stratum lucidum epidermidis); and 5) horny layer (stratum corneum epidermidis). [NIH] Epigastric: Having to do with the upper middle area of the abdomen. [NIH] Epinephrine: The active sympathomimetic hormone from the adrenal medulla in most species. It stimulates both the alpha- and beta- adrenergic systems, causes systemic vasoconstriction and gastrointestinal relaxation, stimulates the heart, and dilates bronchi and cerebral vessels. It is used in asthma and cardiac failure and to delay absorption of local anesthetics. [NIH] 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] Erectile: The inability to get or maintain an erection for satisfactory sexual intercourse. Also called impotence. [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] Erythromycin Ethylsuccinate: A macrolide antibiotic, produced by Streptomyces erythreus. This compound is an ester of erythromycin base and succinic acid. It acts primarily as a bacteriostatic agent. 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] Erythropoietin: Glycoprotein hormone, secreted chiefly by the kidney in the adult and the liver in the fetus, that acts on erythroid stem cells of the bone marrow to stimulate proliferation and differentiation. [NIH] Esophageal: Having to do with the esophagus, the muscular tube through which food
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passes from the throat to the stomach. [NIH] Esophageal Ulcer: A sore in the esophagus. Caused by long-term inflammation or damage from the residue of pills. The ulcer may cause chest pain. [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]
Estrogen: One of the two female sex hormones. [NIH] Estrogen receptor: ER. Protein found on some cancer cells to which estrogen will attach. [NIH]
Ethanol: A clear, colorless liquid rapidly absorbed from the gastrointestinal tract and distributed throughout the body. It has bactericidal activity and is used often as a topical disinfectant. It is widely used as a solvent and preservative in pharmaceutical preparations as well as serving as the primary ingredient in alcoholic beverages. [NIH] 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 nuclear membrane. [NIH] Excipients: Usually inert substances added to a prescription in order to provide suitable consistency to the dosage form; a binder, matrix, base or diluent in pills, tablets, creams, salves, etc. [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] Exhaustion: The feeling of weariness of mind and body. [NIH] Exocrine: Secreting outwardly, via a duct. [EU] 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] Expander: Any of several colloidal substances of high molecular weight. used as a blood or plasma substitute in transfusion for increasing the volume of the circulating blood. called also extender. [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]
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Extracellular Matrix: A meshwork-like substance found within the extracellular space and in association with the basement membrane of the cell surface. It promotes cellular proliferation and provides a supporting structure to which cells or cell lysates in culture dishes adhere. [NIH] Extracellular Matrix Proteins: Macromolecular organic compounds that contain carbon, hydrogen, oxygen, nitrogen, and usually, sulfur. These macromolecules (proteins) form an intricate meshwork in which cells are embedded to construct tissues. Variations in the relative types of macromolecules and their organization determine the type of extracellular matrix, each adapted to the functional requirements of the tissue. The two main classes of macromolecules that form the extracellular matrix are: glycosaminoglycans, usually linked to proteins (proteoglycans), and fibrous proteins (e.g., collagen, elastin, fibronectins and laminin). [NIH] Extracellular Space: Interstitial space between cells, occupied by fluid as well as amorphous and fibrous substances. [NIH] 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] Facial Nerve: The 7th cranial nerve. The facial nerve has two parts, the larger motor root which may be called the facial nerve proper, and the smaller intermediate or sensory root. Together they provide efferent innervation to the muscles of facial expression and to the lacrimal and salivary glands, and convey afferent information for taste from the anterior two-thirds of the tongue and for touch from the external ear. [NIH] Fallopian Tubes: Two long muscular tubes that transport ova from the ovaries to the uterus. They extend from the horn of the uterus to the ovaries and consist of an ampulla, an infundibulum, an isthmus, two ostia, and a pars uterina. The walls of the tubes are composed of three layers: mucosal, muscular, and serosal. [NIH] Family Planning: Programs or services designed to assist the family in controlling reproduction by either improving or diminishing fertility. [NIH] Fat: Total lipids including phospholipids. [NIH] Fatigue: The state of weariness following a period of exertion, mental or physical, characterized by a decreased capacity for work and reduced efficiency to respond to stimuli. [NIH]
Fatty acids: A major component of fats that are used by the body for energy and tissue development. [NIH] Feces: The excrement discharged from the intestines, consisting of bacteria, cells exfoliated from the intestines, secretions, chiefly of the liver, and a small amount of food residue. [EU] Femoral: Pertaining to the femur, or to the thigh. [EU] Femoral Neck Fractures: Fractures of the short, constricted portion of the thigh bone between the femur head and the trochanters. It excludes intertrochanteric fractures which are hip fractures. [NIH] Femoral Nerve: A nerve originating in the lumbar spinal cord (usually L2 to L4) and traveling through the lumbar plexus to provide motor innervation to extensors of the thigh and sensory innervation to parts of the thigh, lower leg, and foot, and to the hip and knee joints. [NIH] Femur: The longest and largest bone of the skeleton, it is situated between the hip and the
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knee. [NIH] Fetus: The developing offspring from 7 to 8 weeks after conception until birth. [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] Fibroblasts: Connective tissue cells which secrete an extracellular matrix rich in collagen and other macromolecules. [NIH] Fibronectin: An adhesive glycoprotein. One form circulates in plasma, acting as an opsonin; another is a cell-surface protein which mediates cellular adhesive interactions. [NIH] Fibrosis: Any pathological condition where fibrous connective tissue invades any organ, usually as a consequence of inflammation or other injury. [NIH] Filarioidea: A superfamily of nematodes of the suborder Spirurina. Its organisms possess a filiform body and a mouth surrounded by papillae. [NIH] Fissure: Any cleft or groove, normal or otherwise; especially a deep fold in the cerebral cortex which involves the entire thickness of the brain wall. [EU] Fistula: Abnormal communication most commonly seen between two internal organs, or between an internal organ and the surface of the body. [NIH] Fleroxacin: A third-generation fluoroquinolone derivative with a broad antimicrobial spectrum. The drug strongly inhibits the DNA-supercoiling activity of DNA gyrase which may account for its antibacterial activity. [NIH] Flow Cytometry: Technique using an instrument system for making, processing, and displaying one or more measurements on individual cells obtained from a cell suspension. Cells are usually stained with one or more fluorescent dyes specific to cell components of interest, e.g., DNA, and fluorescence of each cell is measured as it rapidly transverses the excitation beam (laser or mercury arc lamp). Fluorescence provides a quantitative measure of various biochemical and biophysical properties of the cell, as well as a basis for cell sorting. Other measurable optical parameters include light absorption and light scattering, the latter being applicable to the measurement of cell size, shape, density, granularity, and stain uptake. [NIH] Fluorescence: The property of emitting radiation while being irradiated. The radiation emitted is usually of longer wavelength than that incident or absorbed, e.g., a substance can be irradiated with invisible radiation and emit visible light. X-ray fluorescence is used in diagnosis. [NIH] Fluorescence Polarization: Measurement of the polarization of fluorescent light from solutions or microscopic specimens. It is used to provide information concerning molecular size, shape, and conformation, molecular anisotropy, electronic energy transfer, molecular interaction, including dye and coenzyme binding, and the antigen-antibody reaction. [NIH] Fluorescent Dyes: Dyes that emit light when exposed to light. The wave length of the emitted light is usually longer than that of the incident light. Fluorochromes are substances that cause fluorescence in other substances, i.e., dyes used to mark or label other compounds with fluorescent tags. They are used as markers in biochemistry and immunology. [NIH] Flushing: A transient reddening of the face that may be due to fever, certain drugs, exertion, stress, or a disease process. [NIH] Foam Cells: Lipid-laden macrophages originating from monocytes or from smooth muscle cells. [NIH]
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Focal Adhesions: An anchoring junction of the cell to a non-cellular substrate. It is composed of a specialized area of the plasma membrane where bundles of microfilaments terminate and attach to the transmembrane linkers, integrins, which in turn attach through their extracellular domains to extracellular matrix proteins. [NIH] Fold: A plication or doubling of various parts of the body. [NIH] Food Chain: The sequence of transfers of matter and energy from organism to organism in the form of food. Food chains intertwine locally into a food web because most organisms consume more than one type of animal or plant. Plants, which convert solar energy to food by photosynthesis, are the primary food source. In a predator chain, a plant-eating animal is eaten by a larger animal. In a parasite chain, a smaller organism consumes part of a larger host and may itself be parasitized by smaller organisms. In a saprophytic chain, microorganisms live on dead organic matter. [NIH] Forearm: The part between the elbow and the wrist. [NIH] Fractionation: Dividing the total dose of radiation therapy into several smaller, equal doses delivered over a period of several days. [NIH] Frontal Lobe: The anterior part of the cerebral hemisphere. [NIH] Fructosamine: An amino sugar formed when glucose non-enzymatically reacts with the Nterminal amino group of proteins. The fructose moiety is dervied from glucose by the "classical" Amadori rearrangement. [NIH] Fructose: A type of sugar found in many fruits and vegetables and in honey. Fructose is used to sweeten some diet foods. It is considered a nutritive sweetener because it has calories. [NIH] Fungi: A kingdom of eukaryotic, heterotrophic organisms that live as saprobes or parasites, including mushrooms, yeasts, smuts, molds, etc. They reproduce either sexually or asexually, and have life cycles that range from simple to complex. Filamentous fungi refer to those that grow as multicelluar colonies (mushrooms and molds). [NIH] Fungus: A general term used to denote a group of eukaryotic protists, including mushrooms, yeasts, rusts, moulds, smuts, etc., which are characterized by the absence of chlorophyll and by the presence of a rigid cell wall composed of chitin, mannans, and sometimes cellulose. They are usually of simple morphological form or show some reversible cellular specialization, such as the formation of pseudoparenchymatous tissue in the fruiting body of a mushroom. The dimorphic fungi grow, according to environmental conditions, as moulds or yeasts. [EU] Galactosides: Glycosides formed by the reaction of the hydroxyl group on the anomeric carbon atom of galactose with an alcohol to form an acetal. They include both alpha- and beta-galactosides. [NIH] Gallbladder: The pear-shaped organ that sits below the liver. Bile is concentrated and stored in the gallbladder. [NIH] Gamma Rays: Very powerful and penetrating, high-energy electromagnetic radiation of shorter wavelength than that of x-rays. They are emitted by a decaying nucleus, usually between 0.01 and 10 MeV. They are also called nuclear x-rays. [NIH] Ganglia: Clusters of multipolar neurons surrounded by a capsule of loosely organized connective tissue located outside the central nervous system. [NIH] 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
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capsule enclosing a clear mucinous fluid. [EU] Gap Junctions: Connections between cells which allow passage of small molecules and electric current. Gap junctions were first described anatomically as regions of close apposition between cells with a narrow (1-2 nm) gap between cell membranes. The variety in the properties of gap junctions is reflected in the number of connexins, the family of proteins which form the junctions. [NIH] Gas: Air that comes from normal breakdown of food. The gases are passed out of the body through the rectum (flatus) or the mouth (burp). [NIH] Gas exchange: Primary function of the lungs; transfer of oxygen from inhaled air into the blood and of carbon dioxide from the blood into the lungs. [NIH] Gastric: Having to do with the stomach. [NIH] Gastric Acid: Hydrochloric acid present in gastric juice. [NIH] Gastrin: A hormone released after eating. Gastrin causes the stomach to produce more acid. [NIH]
Gastrointestinal: Refers to the stomach and intestines. [NIH] Gastrointestinal tract: The stomach and intestines. [NIH] 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] Gelatinase A: A secreted endopeptidase homologous with interstitial collagenase, but which possesses an additional fibronectin-like domain. EC 3.4.24.24. [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] Gene: The functional and physical unit of heredity passed from parent to offspring. Genes are pieces of DNA, and most genes contain the information for making a specific protein. [NIH]
Gene Expression: The phenotypic manifestation of a gene or genes by the processes of gene action. [NIH] Gene 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] 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]
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Genotype: The genetic constitution of the individual; the characterization of the genes. [NIH] Gentamicins: A complex of three different closely related aminoglycoside sulfates, Gentamicins C1, C2, and C1(subA), obtained from Micromonospora purpurea and related species. They are broad-spectrum antibiotics, but may cause ear and kidney damage. They act to inhibit protein synthesis (translation (genetics)). [NIH] Germinal Center: The activated center of a lymphoid follicle in secondary lymphoid tissue where B-lymphocytes are stimulated by antigens and helper T cells (T-lymphocytes, helperinducer) are stimulated to generate memory cells. [NIH] Gestation: The period of development of the young in viviparous animals, from the time of fertilization of the ovum until birth. [EU] 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] 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] Glanders: A contagious disease of horses that can be transmitted to humans. It is caused by Pseudomonas mallei and characterized by ulceration of the respiratory mucosa and an eruption of nodules on the skin. [NIH] Glial Fibrillary Acidic Protein: An intermediate filament protein found only in glial cells or cells of glial origin. MW 51,000. [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]
Glomeruli: Plural of glomerulus. [NIH] Glomerulosclerosis: Scarring of the glomeruli. It may result from diabetes mellitus (diabetic glomerulosclerosis) or from deposits in parts of the glomerulus (focal segmental glomerulosclerosis). The most common signs of glomerulosclerosis are proteinuria and kidney failure. [NIH] Glomerulus: A tiny set of looping blood vessels in the nephron where blood is filtered in the kidney. [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] Glutathione Peroxidase: An enzyme catalyzing the oxidation of 2 moles of glutathione in the presence of hydrogen peroxide to yield oxidized glutathione and water. EC 1.11.1.9. [NIH]
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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] Glycosaminoglycans: Heteropolysaccharides which contain an N-acetylated hexosamine in a characteristic repeating disaccharide unit. The repeating structure of each disaccharide involves alternate 1,4- and 1,3-linkages consisting of either N-acetylglucosamine or Nacetylgalactosamine. [NIH] Glycoside: Any compound that contains a carbohydrate molecule (sugar), particularly any such natural product in plants, convertible, by hydrolytic cleavage, into sugar and a nonsugar component (aglycone), and named specifically for the sugar contained, as glucoside (glucose), pentoside (pentose), fructoside (fructose) etc. [EU] Glycosidic: Formed by elimination of water between the anomeric hydroxyl of one sugar and a hydroxyl of another sugar molecule. [NIH] Glycosylation: The chemical or biochemical addition of carbohydrate or glycosyl groups to other chemicals, especially peptides or proteins. Glycosyl transferases are used in this biochemical reaction. [NIH] Goats: Any of numerous agile, hollow-horned ruminants of the genus Capra, closely related to the sheep. [NIH] Gonorrhea: Acute infectious disease characterized by primary invasion of the urogenital tract. The etiologic agent, Neisseria gonorrhoeae, was isolated by Neisser in 1879. [NIH] Governing Board: The group in which legal authority is vested for the control of healthrelated institutions and organizations. [NIH] 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] 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] Grafting: The operation of transfer of tissue from one site to another. [NIH] Gram-negative: Losing the stain or decolorized by alcohol in Gram's method of staining, a primary characteristic of bacteria having a cell wall composed of a thin layer of peptidoglycan covered by an outer membrane of lipoprotein and lipopolysaccharide. [EU] Gram-positive: Retaining the stain or resisting decolorization by alcohol in Gram's method of staining, a primary characteristic of bacteria whose cell wall is composed of a thick layer of peptidologlycan with attached teichoic acids. [EU] 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] Gravidity: Pregnancy; the condition of being pregnant, without regard to the outcome. [EU] Groin: The external junctural region between the lower part of the abdomen and the thigh. [NIH]
Growth: The progressive development of a living being or part of an organism from its earliest stage to maturity. [NIH]
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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]
Haemophilus: A genus of Pasteurellaceae that consists of several species occurring in animals and humans. Its organisms are described as gram-negative, facultatively anaerobic, coccobacillus or rod-shaped, and nonmotile. [NIH] 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] 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 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] Headache Disorders: Common conditions characterized by persistent or recurrent headaches. Headache syndrome classification systems may be based on etiology (e.g., vascular headache, post-traumatic headaches, etc.), temporal pattern (e.g., cluster headache, paroxysmal hemicrania, etc.), and precipitating factors (e.g., cough headache). [NIH] Health Services: Services for the diagnosis and treatment of disease and the maintenance of health. [NIH] Health Status: The level of health of the individual, group, or population as subjectively assessed by the individual or by more objective measures. [NIH] Heart attack: A seizure of weak or abnormal functioning of the heart. [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] 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
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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] 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]
Heparin: Heparinic acid. A highly acidic mucopolysaccharide formed of equal parts of sulfated D-glucosamine and D-glucuronic acid with sulfaminic bridges. The molecular weight ranges from six to twenty thousand. Heparin occurs in and is obtained from liver, lung, mast cells, etc., of vertebrates. Its function is unknown, but it is used to prevent blood clotting in vivo and vitro, in the form of many different salts. [NIH] Hepatic: Refers to the liver. [NIH] Hepatitis: Inflammation of the liver and liver disease involving degenerative or necrotic alterations of hepatocytes. [NIH] Hepatocyte: A liver cell. [NIH] Heredity: 1. The genetic transmission of a particular quality or trait from parent to offspring. 2. The genetic constitution of an individual. [EU] Herpes: Any inflammatory skin disease caused by a herpesvirus and characterized by the formation of clusters of small vesicles. When used alone, the term may refer to herpes simplex or to herpes zoster. [EU] Herpes virus: A member of the herpes family of viruses. [NIH] Herpes Zoster: Acute vesicular inflammation. [NIH] Heterodimer: 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]
Heterogenic: Derived from a different source or species. Also called heterogenous. [NIH] Heterogenous: Derived from a different source or species. Also called heterogenic. [NIH] Heterotrophic: Pertaining to organisms that are consumers and dependent on other organisms for their source of energy (food). [NIH] Hip Fractures: Fractures of the femur head, the femur neck, the trochanters, or the inter- or subtrochanteric region. Excludes fractures of the acetabulum and fractures of the femoral shaft below the subtrochanteric region. For the fractures of the femur neck the specific term femoral neck fractures is available. [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] Histology: The study of tissues and cells under a microscope. [NIH] Homeostasis: The processes whereby the internal environment of an organism tends to remain balanced and stable. [NIH]
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Homodimer: Protein-binding "activation domains" always combine with identical proteins. [NIH]
Homologous: Corresponding in structure, position, origin, etc., as (a) the feathers of a bird and the scales of a fish, (b) antigen and its specific antibody, (c) allelic chromosomes. [EU] Hormone: A substance in the body that regulates certain organs. Hormones such as gastrin help in breaking down food. Some hormones come from cells in the stomach and small intestine. [NIH] Hormone Replacement Therapy: Therapeutic use of hormones to alleviate the effects of hormone deficiency. [NIH] Hormone therapy: Treatment of cancer by removing, blocking, or adding hormones. Also called endocrine therapy. [NIH] Horny layer: The superficial layer of the epidermis containing keratinized cells. [NIH] Horseradish Peroxidase: An enzyme isolated from horseradish which is able to act as an antigen. It is frequently used as a histochemical tracer for light and electron microscopy. Its antigenicity has permitted its use as a combined antigen and marker in experimental immunology. [NIH] Host: Any animal that receives a transplanted graft. [NIH] Human growth hormone: A protein hormone, secreted by the anterior lobe of the pituitary, which promotes growth of the whole body by stimulating protein synthesis. The human gene has already been cloned and successfully expressed in bacteria. [NIH] 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] Hydrocephalus: Excessive accumulation of cerebrospinal fluid within the cranium which may be associated with dilation of cerebral ventricles, intracranial hypertension; headache; lethargy; urinary incontinence; and ataxia (and in infants macrocephaly). This condition may be caused by obstruction of cerebrospinal fluid pathways due to neurologic abnormalities, intracranial hemorrhages; central nervous system infections; brain neoplasms; craniocerebral trauma; and other conditions. Impaired resorption of cerebrospinal fluid from the arachnoid villi results in a communicating form of hydrocephalus. Hydrocephalus ex-vacuo refers to ventricular dilation that occurs as a result of brain substance loss from cerebral infarction and other conditions. [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]
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Hydrolases: Any member of the class of enzymes that catalyze the cleavage of the substrate and the addition of water to the resulting molecules, e.g., esterases, glycosidases (glycoside hydrolases), lipases, nucleotidases, peptidases (peptide hydrolases), and phosphatases (phosphoric monoester hydrolases). EC 3. [NIH] Hydrolysis: The process of cleaving a chemical compound by the addition of a molecule of water. [NIH] 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] Hyperaemia: An excess of blood in a part; engorgement. [EU] Hypercalcemia: Abnormally high level of calcium in the blood. [NIH] Hyperpigmentation: Excessive pigmentation of the skin, usually as a result of increased melanization of the epidermis rather than as a result of an increased number of melanocytes. Etiology is varied and the condition may arise from exposure to light, chemicals or other substances, or from a primary metabolic imbalance. [NIH] Hyperplasia: An increase in the number of cells in a tissue or organ, not due to tumor formation. It differs from hypertrophy, which is an increase in bulk without an increase in the number of cells. [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] 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] Hypotension: Abnormally low blood pressure. [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] 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
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factor, immune RNA) or transplantation of immunocompetent cell producing tissue (thymus or bone marrow). [NIH] Immunoassay: Immunochemical assay or detection of a substance by serologic or immunologic methods. Usually the substance being studied serves as antigen both in antibody production and in measurement of antibody by the test substance. [NIH] Immunocompromised: Having a weakened immune system caused by certain diseases or treatments. [NIH] Immunodeficiency: The decreased ability of the body to fight infection and disease. [NIH] Immunodeficiency syndrome: The inability of the body to produce an immune response. [NIH]
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] Immunology: The study of the body's immune system. [NIH] Immunosuppressive: Describes the ability to lower immune system responses. [NIH] Immunotoxin: An antibody linked to a toxic substance. Some immmunotoxins can bind to cancer cells and kill them. [NIH] Impairment: In the context of health experience, an impairment is any loss or abnormality of psychological, physiological, or anatomical structure or function. [NIH] Implant radiation: A procedure in which radioactive material sealed in needles, seeds, wires, or catheters is placed directly into or near the tumor. Also called [NIH] In situ: In the natural or normal place; confined to the site of origin without invasion of neighbouring tissues. [EU] In Situ Hybridization: A technique that localizes specific nucleic acid sequences within intact chromosomes, eukaryotic cells, or bacterial cells through the use of specific nucleic acid-labeled probes. [NIH] In vitro: In the laboratory (outside the body). The opposite of in vivo (in the body). [NIH] In vivo: In the body. The opposite of in vitro (outside the body or in the laboratory). [NIH] Incision: A cut made in the body during surgery. [NIH] Incubation: The development of an infectious disease from the entrance of the pathogen to the appearance of clinical symptoms. [EU] Indicative: That indicates; that points out more or less exactly; that reveals fairly clearly. [EU] Induction: The act or process of inducing or causing to occur, especially the production of a specific morphogenetic effect in the developing embryo through the influence of evocators or organizers, or the production of anaesthesia or unconsciousness by use of appropriate agents. [EU] 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
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clinically unapparent or result in local cellular injury due to competitive metabolism, toxins, intracellular replication, or antigen-antibody response. The infection may remain localized, subclinical, and temporary if the body's defensive mechanisms are effective. A local infection may persist and spread by extension to become an acute, subacute, or chronic clinical infection or disease state. A local infection may also become systemic when the microorganisms gain access to the lymphatic or vascular system. 2. An infectious disease. [EU]
Infertility: The diminished or absent ability to conceive or produce an offspring while sterility is the complete inability to conceive or produce an offspring. [NIH] Infiltration: The diffusion or accumulation in a tissue or cells of substances not normal to it or in amounts of the normal. Also, the material so accumulated. [EU] 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] 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] Inhalation: The drawing of air or other substances into the lungs. [EU] Initiation: Mutation induced by a chemical reactive substance causing cell changes; being a step in a carcinogenic process. [NIH] Initiator: A chemically reactive substance which may cause cell changes if ingested, inhaled or absorbed into the body; the substance may thus initiate a carcinogenic process. [NIH] Inlay: In dentistry, a filling first made to correspond with the form of a dental cavity and then cemented into the cavity. [NIH] Inner ear: The labyrinth, comprising the vestibule, cochlea, and semicircular canals. [NIH] Innervation: 1. The distribution or supply of nerves to a part. 2. The supply of nervous energy or of nerve stimulus sent to a part. [EU] Inoculum: The spores or tissues of a pathogen that serve to initiate disease in a plant. [NIH] Inorganic: Pertaining to substances not of organic origin. [EU] Inotropic: Affecting the force or energy of muscular contractions. [EU] Insight: The capacity to understand one's own motives, to be aware of one's own psychodynamics, to appreciate the meaning of symbolic behavior. [NIH] Insulator: Material covering the metal conductor of the lead. It is usually polyurethane or silicone. [NIH] Insulin: A protein hormone secreted by beta cells of the pancreas. Insulin plays a major role in the regulation of glucose metabolism, generally promoting the cellular utilization of glucose. It is also an important regulator of protein and lipid metabolism. Insulin is used as a drug to control insulin-dependent diabetes mellitus. [NIH] Insulin-dependent diabetes mellitus: A disease characterized by high levels of blood glucose resulting from defects in insulin secretion, insulin action, or both. Autoimmune, genetic, and environmental factors are involved in the development of type I diabetes. [NIH] Integrins:
A
family
of
transmembrane
glycoproteins
consisting
of
noncovalent
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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] 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-12: A heterodimeric cytokine that stimulates the production of interferon gamma from T-cells and natural killer cells, and also induces differentiation of Th1 helper cells. It is an initiator of cell-mediated immunity. [NIH] Interleukin-2: Chemical mediator produced by activated T lymphocytes and which regulates the proliferation of T cells, as well as playing a role in the regulation of NK cell activity. [NIH] Interleukin-3: A multilineage cell growth factor secreted by lymphocytes, epithelial cells, and astrocytes which stimulates clonal proliferation and differentiation of various types of blood and tissue cells. Also called multi-CSF, it is considered one of the hematopoietic colony stimulating factors. [NIH] Interleukin-4: Soluble factor produced by activated T-lymphocytes that causes proliferation and differentiation of B-cells. Interleukin-4 induces the expression of class II major histocompatibility complex and Fc receptors on B-cells. It also acts on T-lymphocytes, mast cell lines, and several other hematopoietic lineage cells including granulocyte, megakaryocyte, and erythroid precursors, as well as macrophages. [NIH] Interleukin-8: A cytokine that activates neutrophils and attracts neutrophils and Tlymphocytes. It is released by several cell types including monocytes, macrophages, Tlymphocytes, fibroblasts, endothelial cells, and keratinocytes by an inflammatory stimulus. IL-8 is a member of the beta-thromboglobulin superfamily and structurally related to platelet factor 4. [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 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,
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implant radiation, or interstitial radiation therapy. [NIH] Interphase: The interval between two successive cell divisions during which the chromosomes are not individually distinguishable and DNA replication occurs. [NIH] Interstitial: Pertaining to or situated between parts or in the interspaces of a tissue. [EU] Interstitial Collagenase: A member of the metalloproteinase family of enzymes that is principally responsible for cleaving fibrillar collagen. It can degrade interstitial collagens, types I, II and III. EC 3.4.24.7. [NIH] Intestinal: Having to do with the intestines. [NIH] Intestinal Neoplasms: Tumors or cancer of the intestines. [NIH] Intestine: A long, tube-shaped organ in the abdomen that completes the process of digestion. There is both a large intestine and a small intestine. Also called the bowel. [NIH] Intoxication: Poisoning, the state of being poisoned. [EU] Intracellular: Inside a cell. [NIH] Intracranial Hypertension: Increased pressure within the cranial vault. This may result from several conditions, including hydrocephalus; brain edema; intracranial masses; severe systemic hypertension; pseudotumor cerebri; and other disorders. [NIH] Intramuscular: IM. Within or into muscle. [NIH] Intramuscular injection: IM. Injection into a 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]
Involuntary: Reaction occurring without intention or volition. [NIH] Iodine: A nonmetallic element of the halogen group that is represented by the atomic symbol I, atomic number 53, and atomic weight of 126.90. It is a nutritionally essential element, especially important in thyroid hormone synthesis. In solution, it has anti-infective properties and is used topically. [NIH] Iodoacetamide: An alkylating sulfhydryl reagent. Its actions are similar to those of iodoacetate. [NIH] Ion Channels: Gated, ion-selective glycoproteins that traverse membranes. The stimulus for channel gating can be a membrane potential, drug, transmitter, cytoplasmic messenger, or a mechanical deformation. Ion channels which are integral parts of ionotropic neurotransmitter receptors are not included. [NIH] Ions: An atom or group of atoms that have a positive or negative electric charge due to a gain (negative charge) or loss (positive charge) of one or more electrons. Atoms with a positive charge are known as cations; those with a negative charge are anions. [NIH] 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] 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.
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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] 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] Isoenzyme: Different forms of an enzyme, usually occurring in different tissues. The isoenzymes of a particular enzyme catalyze the same reaction but they differ in some of their properties. [NIH] Ivermectin: A mixture of ivermectin component B1a (RN 71827-03-7) and B1b (RN 70209-813), which is a semisynthetic product from Streptomyces avermitilis. A potent macrocyclic lactone disaccharide antiparasitic agent used to prevent and treat parasite infestations in animals. The compound has activity against internal and external parasites and has been found effective against arthropods, insects, nematodes, filarioidea, platyhelminths, and protozoa. [NIH] Joint: The point of contact between elements of an animal skeleton with the parts that surround and support it. [NIH] Kb: A measure of the length of DNA fragments, 1 Kb = 1000 base pairs. The largest DNA fragments are up to 50 kilobases long. [NIH] Keratin: A class of fibrous proteins or scleroproteins important both as structural proteins and as keys to the study of protein conformation. The family represents the principal constituent of epidermis, hair, nails, horny tissues, and the organic matrix of tooth enamel. Two major conformational groups have been characterized, alpha-keratin, whose peptide 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] Kerato: Prefix indicating relationship to the cornea. [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] Kinetics: The study of rate dynamics in chemical or physical systems. [NIH] Labile: 1. Gliding; moving from point to point over the surface; unstable; fluctuating. 2. Chemically unstable. [EU] Labyrinth: The internal ear; the essential part of the organ of hearing. It consists of an osseous and a membranous portion. [NIH]
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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] Leptospirosis: Infections with bacteria of the genus Leptospira. [NIH] Lesion: An area of abnormal tissue change. [NIH] Lethal: Deadly, fatal. [EU] 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] Levofloxacin: A substance used to treat bacterial infections. It belongs to the family of drugs called quinolone antibiotics. [NIH] Library Services: Services offered to the library user. They include reference and circulation. [NIH]
Life cycle: The successive stages through which an organism passes from fertilized ovum or spore to the fertilized ovum or spore of the next generation. [NIH] Life Expectancy: A figure representing the number of years, based on known statistics, to which any person of a given age may reasonably expect to live. [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] Limbic: Pertaining to a limbus, or margin; forming a border around. [EU] Limbic System: A set of forebrain structures common to all mammals that is defined functionally and anatomically. It is implicated in the higher integration of visceral, olfactory, and somatic information as well as homeostatic responses including fundamental survival behaviors (feeding, mating, emotion). For most authors, it includes the amygdala, epithalamus, gyrus cinguli, hippocampal formation (see hippocampus), hypothalamus, parahippocampal gyrus, septal nuclei, anterior nuclear group of thalamus, and portions of the basal ganglia. (Parent, Carpenter's Human Neuroanatomy, 9th ed, p744; NeuroNames, http://rprcsgi.rprc.washington.edu/neuronames/index.html (September 2, 1998)). [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
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independent assortment. [NIH] Lipid: Fat. [NIH] Lipid Peroxidation: Peroxidase catalyzed oxidation of lipids using hydrogen peroxide as an electron acceptor. [NIH] Lipopolysaccharide: Substance consisting of polysaccaride and lipid. [NIH] 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]
Liposome: A spherical particle in an aqueous medium, formed by a lipid bilayer enclosing an aqueous compartment. [EU] Lipoxygenase: An enzyme of the oxidoreductase class that catalyzes reactions between linoleate and other fatty acids and oxygen to form hydroperoxy-fatty acid derivatives. Related enzymes in this class include the arachidonate lipoxygenases, arachidonate 5lipoxygenase, arachidonate 12-lipoxygenase, and arachidonate 15-lipoxygenase. EC 1.13.11.12. [NIH] Lithium: An element in the alkali metals family. It has the atomic symbol Li, atomic number 3, and atomic weight 6.94. Salts of lithium are used in treating manic-depressive disorders. [NIH]
Liver: A large, glandular organ located in the upper abdomen. The liver cleanses the blood and aids in digestion by secreting bile. [NIH] Loa: A genus of parasitic nematodes found throughout the rain-forest areas of the Sudan and the basin of the Congo. L. loa inhabits the subcutaneous tissues, which it traverses freely. [NIH] Lobe: A portion of an organ such as the liver, lung, breast, or brain. [NIH] Localization: The process of determining or marking the location or site of a lesion or disease. May also refer to the process of keeping a lesion or disease in a specific location or site. [NIH] Localized: Cancer which has not metastasized yet. [NIH] Locomotion: Movement or the ability to move from one place or another. It can refer to humans, vertebrate or invertebrate animals, and microorganisms. [NIH] Locomotor: Of or pertaining to locomotion; pertaining to or affecting the locomotive apparatus of the body. [EU] Loiasis: A parasitic infection caused by the nematode Loa loa. The vector in the transmission of this infection is the horsefly (Tabanus) or the deerfly or mango fly (Chrysops). The larvae may be seen just beneath the skin or passing through the conjunctiva. Eye lesions are not uncommon. The disease is generally mild and painless. [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] 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] Luciferase: Any one of several enzymes that catalyze the bioluminescent reaction in certain marine crustaceans, fish, bacteria, and insects. The enzyme is a flavoprotein; it oxidizes luciferins to an electronically excited compound that emits energy in the form of light. The
220 Doxycycline
color of light emitted varies with the organism. The firefly enzyme is a valuable reagent for measurement of ATP concentration. (Dorland, 27th ed) EC 1.13.12.-. [NIH] Lumbar: Pertaining to the loins, the part of the back between the thorax and the pelvis. [EU] Lupus: A form of cutaneous tuberculosis. It is seen predominantly in women and typically involves the nasal, buccal, and conjunctival mucosa. [NIH] Lyme Disease: An infectious disease caused by a spirochete, Borrelia burgdorferi, which is transmitted chiefly by Ixodes dammini and pacificus ticks in the United States and Ixodes ricinis in Europe. It is a disease with early and late cutaneous manifestations plus involvement of the nervous system, heart, eye, and joints in variable combinations. The disease was formerly known as Lyme arthritis and first discovered at Old Lyme, Connecticut. [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]
Lymphadenopathy: Disease or swelling of the lymph nodes. [NIH] Lymphatic: The tissues and organs, including the bone marrow, spleen, thymus, and lymph nodes, that produce and store cells that fight infection and disease. [NIH] Lymphatic system: The tissues and organs that produce, store, and carry white blood cells that fight infection and other diseases. This system includes the bone marrow, spleen, thymus, lymph nodes and a network of thin tubes that carry lymph and white blood cells. These tubes branch, like blood vessels, into all the tissues of the body. [NIH] Lymphoblastic: One of the most aggressive types of non-Hodgkin lymphoma. [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] 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] Lymphotoxin: Soluble substance released by lymphocytes activated by antigens or T-cell mitogens, that is cytotoxic to other cells. It is involved in allergies and chronic inflammatory diseases. Lymphotoxin is antigenically distinct from tumor necrosis factor-alpha (tumor necrosis factor), though they both share a common receptor, biological activities, and significant amino acid sequences. [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] 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] Maculopapular: Both macular and papular, as an eruption consisting of both macules and papules; sometimes erroneously used to designate a papule that is only slightly elevated. [EU]
Magnetic Resonance Imaging: Non-invasive method of demonstrating internal anatomy based on the principle that atomic nuclei in a strong magnetic field absorb pulses of radiofrequency energy and emit them as radiowaves which can be reconstructed into
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computerized images. The concept includes proton spin tomographic techniques. [NIH] Maintenance therapy: Treatment that is given to help a primary (original) treatment keep working. Maintenance therapy is often given to help keep cancer in remission. [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] 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 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 mesothelioma: A rare type of cancer in which malignant cells are found in the sac lining the chest or abdomen. Exposure to airborne asbestos particles increases one's risk of developing malignant mesothelioma. [NIH] Malignant tumor: A tumor capable of metastasizing. [NIH] Mammary: Pertaining to the mamma, or breast. [EU] Mandible: The largest and strongest bone of the face constituting the lower jaw. It supports the lower teeth. [NIH] Manic: Affected with mania. [EU] Manifest: Being the part or aspect of a phenomenon that is directly observable : concretely expressed in behaviour. [EU] 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
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the nervous system that transmits impulses eliciting a specific response; (2) a chemical substance (transmitter substance) that induces activity in an excitable tissue, such as nerve or muscle; or (3) a substance released from cells as the result of the interaction of antigen with antibody or by the action of antigen with a sensitized lymphocyte. [EU] Medical Records: Recording of pertinent information concerning patient's illness or illnesses. [NIH] Medical Staff: Professional medical personnel who provide care to patients in an organized facility, institution or agency. [NIH] 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] Megakaryocytes: Very large bone marrow cells which release mature blood platelets. [NIH] Meiosis: A special method of cell division, occurring in maturation of the germ cells, by means of which each daughter nucleus receives half the number of chromosomes characteristic of the somatic cells of the species. [NIH] Melanin: The substance that gives the skin its color. [NIH] Melanocytes: Epidermal dendritic pigment cells which control long-term morphological color changes by alteration in their number or in the amount of pigment they produce and store in the pigment containing organelles called melanosomes. Melanophores are larger cells which do not exist in mammals. [NIH] Melanosomes: Melanin-containing organelles found in melanocytes and melanophores. [NIH]
Melioidosis: A disease of humans and animals that resembles glanders. It is caused by Burkholderia pseudomallei and may range from a dormant infection to a condition that causes multiple abscesses, pneumonia, and bacteremia. [NIH] Membrane: A very thin layer of tissue that covers a surface. [NIH] Membrane Fluidity: The motion of phospholipid molecules within the lipid bilayer, dependent on the classes of phospholipids present, their fatty acid composition and degree of unsaturation of the acyl chains, the cholesterol concentration, and temperature. [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 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]
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Mental Health: The state wherein the person is well adjusted. [NIH] Mentors: Senior professionals who provide guidance, direction and support to those persons desirous of improvement in academic positions, administrative positions or other career development situations. [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] Mesenteric: Pertaining to the mesentery : a membranous fold attaching various organs to the body wall. [EU] Mesothelioma: A benign (noncancerous) or malignant (cancerous) tumor affecting the lining of the chest or abdomen. Exposure to asbestos particles in the air increases the risk of developing malignant mesothelioma. [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] 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] Methionine: A sulfur containing essential amino acid that is important in many body functions. It is a chelating agent for heavy metals. [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] Microbe: An organism which cannot be observed with the naked eye; e. g. unicellular animals, lower algae, lower fungi, bacteria. [NIH] Microfilaments: The smallest of the cytoskeletal filaments. They are composed chiefly of actin. [NIH] Micronuclei: Nuclei, separate from and additional to the main nucleus of a cell, produced during the telophase of mitosis or meiosis by lagging chromosomes or chromosome fragments derived from spontaneous or experimentally induced chromosomal structural changes. This concept also includes the smaller, reproductive nuclei found in multinucleate protozoans. [NIH] Microorganism: An organism that can be seen only through a microscope. Microorganisms include bacteria, protozoa, algae, and fungi. Although viruses are not considered living organisms, they are sometimes classified as microorganisms. [NIH]
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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] Micturition: The passage of urine; urination. [EU] Migrans: Infestation of the dermis by various larvae, characterized by bizarre red irregular lines which are broad at one end and fade at the other, produced by burrowing larvae. [NIH] 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] Minocycline: A semisynthetic staphylococcus infections. [NIH]
antibiotic
effective
against
tetracycline-resistant
Miscarriage: Spontaneous expulsion of the products of pregnancy before the middle of the second trimester. [NIH] Mitochondria: Parts of a cell where aerobic production (also known as cell respiration) takes place. [NIH] Mitochondrial Swelling: Increase in volume of mitochondria due to an influx of fluid; it occurs in hypotonic solutions due to osmotic pressure and in isotonic solutions as a result of altered permeability of the membranes of respiring mitochondria. [NIH] Mitosis: A method of indirect cell division by means of which the two daughter nuclei normally receive identical complements of the number of chromosomes of the somatic cells of the species. [NIH] Mitotic: Cell resulting from mitosis. [NIH] Mitotic Spindle Apparatus: An organelle consisting of three components: (1) the astral microtubules, which form around each centrosome and extend to the periphery; (2) the polar microtubules which extend from one spindle pole to the equator; and (3) the kinetochore microtubules, which connect the centromeres of the various chromosomes to either centrosome. [NIH] Mobility: Capability of movement, of being moved, or of flowing freely. [EU] Modification: A change in an organism, or in a process in an organism, that is acquired from its own activity or environment. [NIH] Modulator: A specific inductor that brings out characteristics peculiar to a definite region. [EU]
Molecular: Of, pertaining to, or composed of molecules : a very small mass of matter. [EU] 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]
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Monocyte: A type of white blood cell. [NIH] Mononuclear: A cell with one nucleus. [NIH] Monosomy: The condition in which one chromosome of a pair is missing. In a normally diploid cell it is represented symbolically as 2N-1. [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] Mouth Ulcer: A localized necrotic lesion of the skin or a mucous surface. [NIH] Mucinous: Containing or resembling mucin, the main compound in mucus. [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] Mucolytic: Destroying or dissolving mucin; an agent that so acts : a mucopolysaccharide or glycoprotein, the chief constituent of mucus. [EU] Mucopurulent: Containing both mucus and pus. [EU] Mucosa: A mucous membrane, or tunica mucosa. [EU] Mucus: The viscous secretion of mucous membranes. It contains mucin, white blood cells, water, inorganic salts, and exfoliated cells. [NIH] Multicenter study: A clinical trial that is carried out at more than one medical institution. [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 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] Mutagenesis: Process of generating genetic mutations. It may occur spontaneously or be induced by mutagens. [NIH] Mutagens: Chemical agents that increase the rate of genetic mutation by interfering with the function of nucleic acids. A clastogen is a specific mutagen that causes breaks in chromosomes. [NIH] 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]
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Mycoplasma: A genus of gram-negative, facultatively anaerobic bacteria bounded by a plasma membrane only. Its organisms are parasites and pathogens, found on the mucous membranes of humans, animals, and birds. [NIH] Myelin: The fatty substance that covers and protects nerves. [NIH] 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] Myocardium: The muscle tissue of the heart composed of striated, involuntary muscle known as cardiac muscle. [NIH] Myometrium: The smooth muscle coat of the uterus, which forms the main mass of the organ. [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 is a characteristic feature of myotonic disorders. [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] Naloxone: A specific opiate antagonist that has no agonist activity. It is a competitive antagonist at mu, delta, and kappa opioid receptors. [NIH] Naltrexone: Derivative of noroxymorphone that is the N-cyclopropylmethyl congener of naloxone. It is a narcotic antagonist that is effective orally, longer lasting and more potent than naloxone, and has been proposed for the treatment of heroin addiction. The FDA has approved naltrexone for the treatment of alcohol dependence. [NIH] Narcotic: 1. Pertaining to or producing narcosis. 2. An agent that produces insensibility or stupor, applied especially to the opioids, i.e. to any natural or synthetic drug that has morphine-like actions. [EU] Nasal 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] Natural killer cells: NK cells. A type of white blood cell that contains granules with enzymes that can kill tumor cells or microbial cells. Also called large granular lymphocytes (LGL). [NIH] 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
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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] 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] 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] Nerve: A cordlike structure of nervous tissue that connects parts of the nervous system with other tissues of the body and conveys nervous impulses to, or away from, these tissues. [NIH] Nerve Endings: Specialized terminations of peripheral neurons. Nerve endings include neuroeffector junction(s) by which neurons activate target organs and sensory receptors which transduce information from the various sensory modalities and send it centrally in the nervous system. Presynaptic nerve endings are presynaptic terminals. [NIH] Nervous System: The entire nerve apparatus composed of the brain, spinal cord, nerves and ganglia. [NIH] Netilmicin: Semisynthetic 1-N-ethyl derivative of sisomycin, an aminoglycoside antibiotic with action similar to gentamicin, but less ear and kidney toxicity. [NIH] Networks: Pertaining to a nerve or to the nerves, a meshlike structure of interlocking fibers or strands. [NIH] Neural: 1. Pertaining to a nerve or to the nerves. 2. Situated in the region of the spinal axis, as the neutral arch. [EU] 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] Neuromuscular: Pertaining to muscles and nerves. [EU]
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Neuromuscular Junction: The synapse between a neuron and a muscle. [NIH] Neuronal: Pertaining to a neuron or neurons (= conducting cells of the nervous system). [EU] Neurons: The basic cellular units of nervous tissue. Each neuron consists of a body, an axon, and dendrites. Their purpose is to receive, conduct, and transmit impulses in the nervous system. [NIH] Neuropathy: A problem in any part of the nervous system except the brain and spinal cord. Neuropathies can be caused by infection, toxic substances, or disease. [NIH] Neuropeptide: A member of a class of protein-like molecules made in the brain. Neuropeptides consist of short chains of amino acids, with some functioning as neurotransmitters and some functioning as hormones. [NIH] Neurophysiology: The scientific discipline concerned with the physiology of the nervous system. [NIH] Neuroretinitis: Inflammation of the optic nerve head and adjacent retina. [NIH] Neurotoxic: Poisonous or destructive to nerve tissue. [EU] Neurotransmitters: Endogenous signaling molecules that alter the behavior of neurons or effector cells. Neurotransmitter is used here in its most general sense, including not only messengers that act directly to regulate ion channels, but also those that act through second messenger systems, and those that act at a distance from their site of release. Included are neuromodulators, neuroregulators, neuromediators, and neurohumors, whether or not acting at synapses. [NIH] Neutrons: Electrically neutral elementary particles found in all atomic nuclei except light hydrogen; the mass is equal to that of the proton and electron combined and they are unstable when isolated from the nucleus, undergoing beta decay. Slow, thermal, epithermal, and fast neutrons refer to the energy levels with which the neutrons are ejected from heavier nuclei during their decay. [NIH] Neutrophil: A type of white blood cell. [NIH] Neutrophil Collagenase: A member of the matrix metalloproteinases that cleaves triplehelical collagens types I, II, and III. EC 3.4.24.34. [NIH] Nickel: A trace element with the atomic symbol Ni, atomic number 28, and atomic weight 58.69. It is a cofactor of the enzyme urease. [NIH] Night Blindness: Anomaly of vision in which there is a pronounced inadequacy or complete absence of dark-adaptation. [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] Nocturia: Excessive urination at night. [EU] Norepinephrine: Precursor of epinephrine that is secreted by the adrenal medulla and is a widespread central and autonomic neurotransmitter. Norepinephrine is the principal
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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] Nucleates: Bacteria-inducing ice nucleation at warm temperatures (between zero and minus ten degrees C.). [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] Nucleotidases: A class of enzymes that catalyze the conversion of a nucleotide and water to a nucleoside and orthophosphate. EC 3.1.3.-. [NIH] Nucleus: A body of specialized protoplasm found in nearly all cells and containing the chromosomes. [NIH] Nucleus Accumbens: Collection of pleomorphic cells in the caudal part of the anterior horn of the lateral ventricle, in the region of the olfactory tubercle, lying between the head of the caudate nucleus and the anterior perforated substance. It is part of the so-called ventral striatum, a composite structure considered part of the basal ganglia. [NIH] Ocular: 1. Of, pertaining to, or affecting the eye. 2. Eyepiece. [EU] Ofloxacin: An orally administered broad-spectrum quinolone antibacterial drug active against most gram-negative and gram-positive bacteria. [NIH] 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] Oligo: Chemical and mineral elements that exist in minimal (oligo) quantities in the body, in foods, in the air, in soil; name applied to any element observed as a microconstituent of plant or animal tissue and of beneficial, harmful, or even doubtful significance. [NIH] Oligosaccharides: Carbohydrates consisting of between two and ten monosaccharides connected by either an alpha- or beta-glycosidic link. They are found throughout nature in both the free and bound form. [NIH] Onchocerciasis: Infection with nematodes of the genus Onchocerca. Characteristics include
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the presence of firm subcutaneous nodules filled with adult worms, pruritus, and ocular lesions. [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] Opacity: Degree of density (area most dense taken for reading). [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] Opsin: A protein formed, together with retinene, by the chemical breakdown of metarhodopsin. [NIH] Optic Chiasm: The X-shaped structure formed by the meeting of the two optic nerves. At the optic chiasm the fibers from the medial part of each retina cross to project to the other side of the brain while the lateral retinal fibers continue on the same side. As a result each half of the brain receives information about the contralateral visual field from both eyes. [NIH]
Optic Nerve: The 2nd cranial nerve. The optic nerve conveys visual information from the retina to the brain. The nerve carries the axons of the retinal ganglion cells which sort at the optic chiasm and continue via the optic tracts to the brain. The largest projection is to the lateral geniculate nuclei; other important targets include the superior colliculi and the suprachiasmatic nuclei. Though known as the second cranial nerve, it is considered part of the central nervous system. [NIH] 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] Orderly: A male hospital attendant. [NIH] Organelles: Specific particles of membrane-bound organized living substances present in eukaryotic cells, such as the mitochondria; the golgi apparatus; endoplasmic reticulum; lysomomes; plastids; and vacuoles. [NIH] Ornithosis: Infection with Chlamydophila psittaci (formerly Chlamydia psittaci), transmitted to man by inhalation of dust-borne contaminated nasal secretions or excreta of infected birds. This infection results in a febrile illness characterized by pneumonitis and systemic manifestations. [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] 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] Osteogenic sarcoma: A malignant tumor of the bone. Also called osteosarcoma. [NIH] Osteoporosis: Reduction of bone mass without alteration in the composition of bone, leading to fractures. Primary osteoporosis can be of two major types: postmenopausal
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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] 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 secrete some of the female sex hormones. [NIH] Overexpress: An excess of a particular protein on the surface of a cell. [NIH] Overweight: An excess of body weight but not necessarily body fat; a body mass index of 25 to 29.9 kg/m2. [NIH] Ovum: A female germ cell extruded from the ovary at ovulation. [NIH] Oxacillin: An antibiotic similar to flucloxacillin used in resistant staphylococci infections. [NIH]
Oxidation: The act of oxidizing or state of being oxidized. Chemically it consists in the increase of positive charges on an atom or the loss of negative charges. Most biological oxidations are accomplished by the removal of a pair of hydrogen atoms (dehydrogenation) from a molecule. Such oxidations must be accompanied by reduction of an acceptor molecule. Univalent o. indicates loss of one electron; divalent o., the loss of two electrons. [EU]
Oxidative 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] Oxytetracycline: An antibiotic substance isolated from the actinomycete Streptomyces rimosus and used in a wide variety of clinical conditions. [NIH] Oxytocin: A nonapeptide posterior pituitary hormone that causes uterine contractions and stimulates lactation. [NIH] Pachymeningitis: Inflammation of the dura mater of the brain, the spinal cord or the optic nerve. [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] Palsy: Disease of the peripheral nervous system occurring usually after many years of increased lead absorption. [NIH] Pancreas: A mixed exocrine and endocrine gland situated transversely across the posterior abdominal wall in the epigastric and hypochondriac regions. The endocrine portion is comprised of the Islets of Langerhans, while the exocrine portion is a compound acinar gland that secretes digestive enzymes. [NIH] Panniculitis: General term for inflammation of adipose tissue, usually of the skin, characterized by reddened subcutaneous nodules. [NIH]
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Papilla: A small nipple-shaped elevation. [NIH] Papillary: Pertaining to or resembling papilla, or nipple. [EU] 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] 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] Parity: The number of offspring a female has borne. It is contrasted with gravidity, which refers to the number of pregnancies, regardless of outcome. [NIH] Parotid: The space that contains the parotid gland, the facial nerve, the external carotid artery, and the retromandibular vein. [NIH] Particle: A tiny mass of material. [EU] Parturition: The act or process of given birth to a child. [EU] Patch: A piece of material used to cover or protect a wound, an injured part, etc.: a patch over the eye. [NIH] Pathogen: Any disease-producing microorganism. [EU] Pathogenesis: The cellular events and reactions that occur in the development of disease. [NIH]
Pathologic: 1. Indicative of or caused by a morbid condition. 2. Pertaining to pathology (= branch of medicine that treats the essential nature of the disease, especially the structural and functional changes in tissues and organs of the body caused by the disease). [EU] 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]
Pelvic: Pertaining to the pelvis. [EU] Pelvic inflammatory disease: A bacteriological disease sometimes associated with intrauterine device (IUD) usage. [NIH] Penicillin: An antibiotic drug used to treat infection. [NIH] Penis: The external reproductive organ of males. It is composed of a mass of erectile tissue enclosed in three cylindrical fibrous compartments. Two of the three compartments, the corpus cavernosa, are placed side-by-side along the upper part of the organ. The third compartment below, the corpus spongiosum, houses the urethra. [NIH] Pentoxifylline: A methylxanthine derivative that inhibits phosphodiesterase and affects blood rheology. It improves blood flow by increasing erythrocyte and leukocyte flexibility. It
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also inhibits platelet aggregation. Pentoxifylline modulates immunologic activity by stimulating cytokine production. [NIH] Peptic: Pertaining to pepsin or to digestion; related to the action of gastric juices. [EU] Peptic Ulcer: Ulcer that occurs in those portions of the alimentary tract which come into contact with gastric juice containing pepsin and acid. It occurs when the amount of acid and pepsin is sufficient to overcome the gastric mucosal barrier. [NIH] 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 Hydrolases: A subclass of enzymes from the hydrolase class that catalyze the hydrolysis of peptide bonds. Exopeptidases and endopeptidases make up the sub-subclasses for this group. EC 3.4. [NIH] Percutaneous: Performed through the skin, as injection of radiopacque material in radiological examination, or the removal of tissue for biopsy accomplished by a needle. [EU] Perennial: Lasting through the year of for several years. [EU] Perforation: 1. The act of boring or piercing through a part. 2. A hole made through a part or substance. [EU] Pericardial Effusion: Presence of fluid within the pericardium. [NIH] Pericardium: The fibroserous sac surrounding the heart and the roots of the great vessels. [NIH]
Perinatal: Pertaining to or occurring in the period shortly before and after birth; variously defined as beginning with completion of the twentieth to twenty-eighth week of gestation and ending 7 to 28 days after birth. [EU] Periodontal disease: Disease involving the supporting structures of the teeth (as the gums and periodontal membranes). [NIH] Periodontal Pocket: An abnormal extension of a gingival sulcus accompanied by the apical migration of the epithelial attachment and bone resorption. [NIH] Periodontics: A dental specialty concerned with the histology, physiology, and pathology of the tissues that support, attach, and surround the teeth, and of the treatment and prevention of disease affecting these tissues. [NIH] Periodontitis: Inflammation of the periodontal membrane; also called periodontitis simplex. [NIH]
Peripheral blood: Blood circulating throughout the body. [NIH] Peripheral Nervous System: The nervous system outside of the brain and spinal cord. The peripheral nervous system has autonomic and somatic divisions. The autonomic nervous system includes the enteric, parasympathetic, and sympathetic subdivisions. The somatic nervous system includes the cranial and spinal nerves and their ganglia and the peripheral sensory receptors. [NIH] 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] 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]
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PH: The symbol relating the hydrogen ion (H+) concentration or activity of a solution to that of a given standard solution. Numerically the pH is approximately equal to the negative logarithm of H+ concentration expressed in molarity. pH 7 is neutral; above it alkalinity increases and below it acidity increases. [EU] Phagocyte: An immune system cell that can surround and kill microorganisms and remove dead cells. Phagocytes include macrophages. [NIH] 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] Pharmacodynamic: Is concerned with the response of living tissues to chemical stimuli, that is, the action of drugs on the living organism in the absence of disease. [NIH] Pharmacokinetic: The mathematical analysis of the time courses of absorption, distribution, and elimination of drugs. [NIH] Pharmacologic: Pertaining to pharmacology or to the properties and reactions of drugs. [EU] Pharynx: The hollow tube about 5 inches long that starts behind the nose and ends at the top of the trachea (windpipe) and esophagus (the tube that goes to the stomach). [NIH] Phenotype: The outward appearance of the individual. It is the product of interactions between genes and between the genotype and the environment. This includes the killer phenotype, characteristic of yeasts. [NIH] Phenylalanine: An aromatic amino acid that is essential in the animal diet. It is a precursor of melanin, dopamine, noradrenalin, and thyroxine. [NIH] Phorbol: Class of chemicals that promotes the development of tumors. [NIH] 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] Phosphoric Monoester Hydrolases: A group of hydrolases which catalyze the hydrolysis of monophosphoric esters with the production of one mole of orthophosphate. EC 3.1.3. [NIH] Phosphorus: A non-metallic element that is found in the blood, muscles, nevers, bones, and teeth, and is a component of adenosine triphosphate (ATP; the primary energy source for the body's cells.) [NIH] Phosphorylated: Attached to a phosphate group. [NIH] Phosphorylates: Attached to a phosphate group. [NIH] Phosphorylation: The introduction of a phosphoryl group into a compound through the formation of an ester bond between the compound and a phosphorus moiety. [NIH] Photocoagulation: Using a special strong beam of light (laser) to seal off bleeding blood vessels such as in the eye. The laser can also burn away blood vessels that should not have
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grown in the eye. This is the main treatment for diabetic retinopathy. [NIH] Photoreceptor: Receptor capable of being activated by light stimuli, as a rod or cone cell of the eye. [NIH] Photosensitivity: An abnormal cutaneous response involving the interaction between photosensitizing substances and sunlight or filtered or artificial light at wavelengths of 280400 mm. There are two main types : photoallergy and photoxicity. [EU] 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] Pilot study: The initial study examining a new method or treatment. [NIH] Placenta: A highly vascular fetal organ through which the fetus absorbs oxygen and other nutrients and excretes carbon dioxide and other wastes. It begins to form about the eighth day of gestation when the blastocyst adheres to the decidua. [NIH] Plague: An acute infectious disease caused by Yersinia pestis that affects humans, wild rodents, and their ectoparasites. This condition persists due to its firm entrenchment in sylvatic rodent-flea ecosystems throughout the world. Bubonic plague is the most common form. [NIH] Plants: Multicellular, eukaryotic life forms of the kingdom Plantae. They are characterized by a mainly photosynthetic mode of nutrition; essentially unlimited growth at localized regions of cell divisions (meristems); cellulose within cells providing rigidity; the absence of organs of locomotion; absense of nervous and sensory systems; and an alteration of haploid and diploid generations. [NIH] Plaque: A clear zone in a bacterial culture grown on an agar plate caused by localized destruction of bacterial cells by a bacteriophage. The concentration of infective virus in a fluid can be estimated by applying the fluid to a culture and counting the number of. [NIH] Plasma: The clear, yellowish, fluid part of the blood that carries the blood cells. The proteins that form blood clots are in plasma. [NIH] Plasma cells: A type of white blood cell that produces antibodies. [NIH] Plasma protein: One of the hundreds of different proteins present in blood plasma, including carrier proteins ( such albumin, transferrin, and haptoglobin), fibrinogen and other coagulation factors, complement components, immunoglobulins, enzyme inhibitors, precursors of substances such as angiotension and bradykinin, and many other types of proteins. [EU] Plasmid: An autonomously replicating, extra-chromosomal DNA molecule found in many bacteria. Plasmids are widely used as carriers of cloned genes. [NIH] Plasmin: A product of the lysis of plasminogen (profibrinolysin) by plasminogen activators. It is composed of two polypeptide chains, light (B) and heavy (A), with a molecular weight of 75,000. It is the major proteolytic enzyme involved in blood clot retraction or the lysis of fibrin and quickly inactivated by antiplasmins. EC 3.4.21.7. [NIH] Plasminogen: Precursor of fibrinolysin (plasmin). It is a single-chain beta-globulin of molecular weight 80-90,000 found mostly in association with fibrinogen in plasma;
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plasminogen activators change it to fibrinolysin. It is used in wound debriding and has been investigated as a thrombolytic agent. [NIH] Plasminogen Activators: A heterogeneous group of proteolytic enzymes that convert plasminogen to plasmin. They are concentrated in the lysosomes of most cells and in the vascular endothelium, particularly in the vessels of the microcirculation. EC 3.4.21.-. [NIH] Plasticity: In an individual or a population, the capacity for adaptation: a) through gene changes (genetic plasticity) or b) through internal physiological modifications in response to changes of environment (physiological plasticity). [NIH] Platelet Activation: A series of progressive, overlapping events triggered by exposure of the platelets to subendothelial tissue. These events include shape change, adhesiveness, aggregation, and release reactions. When carried through to completion, these events lead to the formation of a stable hemostatic plug. [NIH] Platelet Aggregation: The attachment of platelets to one another. This clumping together can be induced by a number of agents (e.g., thrombin, collagen) and is part of the mechanism leading to the formation of a thrombus. [NIH] Platelet Factor 4: A high-molecular-weight proteoglycan-platelet factor complex which is released from blood platelets by thrombin. It acts as a mediator in the heparin-neutralizing capacity of the blood and plays a role in platelet aggregation. At high ionic strength (I=0.75), the complex dissociates into the active component (molecular weight 29,000) and the proteoglycan carrier (chondroitin 4-sulfate, molecular weight 350,000). The molecule exists in the form of a dimer consisting of 8 moles of platelet factor 4 and 2 moles of proteoglycan. [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]
Platyhelminths: A phylum of acoelomate, bilaterally symmetrical flatworms, without a definite anus. It includes three classes: Cestoda, Turbellaria, and Trematoda. [NIH] Pleated: Particular three-dimensional pattern of amyloidoses. [NIH] Pleomorphic: Occurring in various distinct forms. In terms of cells, having variation in the size and shape of cells or their nuclei. [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] Plexus: A network or tangle; a general term for a network of lymphatic vessels, nerves, or veins. [EU]
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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] Polycystic: An inherited disorder characterized by many grape-like clusters of fluid-filled cysts that make both kidneys larger over time. These cysts take over and destroy working kidney tissue. PKD may cause chronic renal failure and end-stage renal disease. [NIH] Polymerase: An enzyme which catalyses the synthesis of DNA using a single DNA strand as a template. The polymerase copies the template in the 5'-3'direction provided that sufficient quantities of free nucleotides, dATP and dTTP are present. [NIH] Polymerase Chain Reaction: In vitro method for producing large amounts of specific DNA or RNA fragments of defined length and sequence from small amounts of short oligonucleotide flanking sequences (primers). The essential steps include thermal denaturation of the double-stranded target molecules, annealing of the primers to their complementary sequences, and extension of the annealed primers by enzymatic synthesis with DNA polymerase. The reaction is efficient, specific, and extremely sensitive. Uses for the reaction include disease diagnosis, detection of difficult-to-isolate pathogens, mutation analysis, genetic testing, DNA sequencing, and analyzing evolutionary relationships. [NIH] Polymers: Compounds formed by the joining of smaller, usually repeating, units linked by covalent bonds. These compounds often form large macromolecules (e.g., polypeptides, proteins, plastics). [NIH] 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] 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] Portal Vein: A short thick vein formed by union of the superior mesenteric vein and the splenic vein. [NIH] Posterior: Situated in back of, or in the back part of, or affecting the back or dorsal surface of the body. In lower animals, it refers to the caudal end of the body. [EU] Postmenopausal: Refers to the time after menopause. Menopause is the time in a woman's life when menstrual periods stop permanently; also called "change of life." [NIH] Postnatal: Occurring after birth, with reference to the newborn. [EU] Postoperative: After surgery. [NIH] Postsynaptic: Nerve potential generated by an inhibitory hyperpolarizing stimulation. [NIH] Post-synaptic: Nerve potential generated by an inhibitory hyperpolarizing stimulation. [NIH] 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
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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] Povidone: A polyvinyl polymer of variable molecular weight; used as suspending and dispersing agent and vehicle for pharmaceuticals; also used as blood volume expander. [NIH] Povidone-Iodine: An iodinated polyvinyl polymer used as topical antiseptic in surgery and for skin and mucous membrane infections, also as aerosol. The iodine may be radiolabeled for research purposes. [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] 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] Prefrontal Cortex: The rostral part of the frontal lobe, bounded by the inferior precentral fissure in humans, which receives projection fibers from the mediodorsal nucleus of the thalamus. The prefrontal cortex receives afferent fibers from numerous structures of the diencephalon, mesencephalon, and limbic system as well as cortical afferents of visual, auditory, and somatic origin. [NIH] Prenatal: Existing or occurring before birth, with reference to the fetus. [EU] Presynaptic: Situated proximal to a synapse, or occurring before the synapse is crossed. [EU] Prevalence: The total number of cases of a given disease in a specified population at a designated time. It is differentiated from incidence, which refers to the number of new cases in the population at a given time. [NIH] Prickle: Several layers of the epidermis where the individual cells are connected by cell bridges. [NIH] Primary endpoint: The main result that is measured at the end of a study to see if a given treatment worked (e.g., the number of deaths or the difference in survival between the treatment group and the control group). What the primary endpoint will be is decided before the study begins. [NIH] Primary tumor: The original tumor. [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] Probenecid: The prototypical uricosuric agent. It inhibits the renal excretion of organic anions and reduces tubular reabsorption of urate. Probenecid has also been used to treat
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patients with renal impairment, and, because it reduces the renal tubular excretion of other drugs, has been used as an adjunct to antibacterial therapy. [NIH] Procaine: A local anesthetic of the ester type that has a slow onset and a short duration of action. It is mainly used for infiltration anesthesia, peripheral nerve block, and spinal block. (From Martindale, The Extra Pharmacopoeia, 30th ed, p1016). [NIH] 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] Progestogen: A term applied to any substance possessing progestational activity. [EU] 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] Proliferating Cell Nuclear Antigen: Nuclear antigen with a role in DNA synthesis, DNA repair, and cell cycle progression. PCNA is required for the coordinated synthesis of both leading and lagging strands at the replication fork during DNA replication. PCNA expression correlates with the proliferation activity of several malignant and non-malignant cell types. [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] 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 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] Prostate: A gland in males that surrounds the neck of the bladder and the urethra. It secretes a substance that liquifies coagulated semen. It is situated in the pelvic cavity behind the lower part of the pubic symphysis, above the deep layer of the triangular ligament, and rests upon the rectum. [NIH] Protease: Proteinase (= any enzyme that catalyses the splitting of interior peptide bonds in a protein). [EU] 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]
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Protein Isoforms: Different forms of a protein that may be produced from different genes, or from the same gene by alternative splicing. [NIH] Protein S: The vitamin K-dependent cofactor of activated protein C. Together with protein C, it inhibits the action of factors VIIIa and Va. A deficiency in protein S can lead to recurrent venous and arterial thrombosis. [NIH] Protein Subunits: Single chains of amino acids that are the units of a multimeric protein. They can be identical or non-identical subunits. [NIH] Proteins: Polymers of amino acids linked by peptide bonds. The specific sequence of amino acids determines the shape and function of the protein. [NIH] Proteinuria: The presence of protein in the urine, indicating that the kidneys are not 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] 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] 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] 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] Pruritus: An intense itching sensation that produces the urge to rub or scratch the skin to obtain relief. [NIH] Pseudotumor Cerebri: A condition marked by raised intracranial pressure and characterized clinically by headaches; nausea; papilledema, peripheral constriction of the visual fields, transient visual obscurations, and pulsatile tinnitus. Obesity is frequently associated with this condition, which primarily affects women between 20 and 44 years of age. Chronic papilledema may lead to optic nerve injury (optic nerve diseases) and visual loss (blindness). [NIH] Psittaci: Causal agent of ornithosis. [NIH] 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] Puberty: The period during which the secondary sex characteristics begin to develop and
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the capability of sexual reproduction is attained. [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] 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] Purpura: Purplish or brownish red discoloration, easily visible through the epidermis, caused by hemorrhage into the tissues. [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] Quality of Life: A generic concept reflecting concern with the modification and enhancement of life attributes, e.g., physical, political, moral and social environment. [NIH] Quiescent: Marked by a state of inactivity or repose. [EU] Quinidine: An optical isomer of quinine, extracted from the bark of the Cinchona tree and similar plant species. This alkaloid dampens the excitability of cardiac and skeletal muscles by blocking sodium and potassium currents across cellular membranes. It prolongs cellular action potential, and decreases automaticity. Quinidine also blocks muscarinic and alphaadrenergic neurotransmission. [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] Race: A population within a species which exhibits general similarities within itself, but is
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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] 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] 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] Raloxifene: A second generation selective estrogen receptor modulator (SERM) used to 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] 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] Randomized clinical trial: A study in which the participants are assigned by chance to separate groups that compare different treatments; neither the researchers nor the participants can choose which group. Using chance to assign people to groups means that the groups will be similar and that the treatments they receive can be compared objectively. At the time of the trial, it is not known which treatment is best. It is the patient's choice to be in a randomized trial. [NIH] Reabsorption: 1. The act or process of absorbing again, as the selective absorption by the kidneys of substances (glucose, proteins, sodium, etc.) already secreted into the renal tubules, and their return to the circulating blood. 2. Resorption. [EU] 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] Recombinant: A cell or an individual with a new combination of genes not found together in either parent; usually applied to linked genes. [EU]
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Recombinant Proteins: Proteins prepared by recombinant DNA technology. [NIH] Recombination: The formation of new combinations of genes as a result of segregation in crosses between genetically different parents; also the rearrangement of linked genes due to crossing-over. [NIH] Reconstitution: 1. A type of regeneration in which a new organ forms by the rearrangement of tissues rather than from new formation at an injured surface. 2. The restoration to original form of a substance previously altered for preservation and storage, as the restoration to a liquid state of blood serum or plasma that has been dried and stored. [EU] Rectum: The last 8 to 10 inches of the large intestine. [NIH] Recurrence: The return of a sign, symptom, or disease after a remission. [NIH] Reductase: Enzyme converting testosterone to dihydrotestosterone. [NIH] Refer: To send or direct for treatment, aid, information, de decision. [NIH] Refraction: A test to determine the best eyeglasses or contact lenses to correct a refractive error (myopia, hyperopia, or astigmatism). [NIH] Regeneration: The natural renewal of a structure, as of a lost tissue or part. [EU] Regimen: A treatment plan that specifies the dosage, the schedule, and the duration of treatment. [NIH] Regurgitation: A backward flowing, as the casting up of undigested food, or the backward flowing of blood into the heart, or between the chambers of the heart when a valve is incompetent. [EU] Remission: A decrease in or disappearance of signs and symptoms of cancer. In partial remission, some, but not all, signs and symptoms of cancer have disappeared. In complete remission, all signs and symptoms of cancer have disappeared, although there still may be cancer in the body. [NIH] Renal failure: Progressive renal insufficiency and uremia, due to irreversible and progressive renal glomerular tubular or interstitial disease. [NIH] Renal tubular: A defect in the kidneys that hinders their normal excretion of acids. Failure to excrete acids can lead to weak bones, kidney stones, and poor growth in children. [NIH] Renin: An enzyme which is secreted by the kidney and is formed from prorenin in plasma and kidney. The enzyme cleaves the Leu-Leu bond in angiotensinogen to generate angiotensin I. EC 3.4.23.15. (Formerly EC 3.4.99.19). [NIH] 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] 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] Repopulation: The replacement of functional cells, usually by proliferation, following or during irradiation. [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] Resorption: The loss of substance through physiologic or pathologic means, such as loss of
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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] Respiratory failure: Inability of the lungs to conduct gas exchange. [NIH] Response Elements: Nucleotide sequences, usually upstream, which are recognized by specific regulatory transcription factors, thereby causing gene response to various regulatory agents. These elements may be found in both promotor and enhancer regions. [NIH]
Restoration: Broad term applied to any inlay, crown, bridge or complete denture which restores or replaces loss of teeth or oral tissues. [NIH] Retina: The ten-layered nervous tissue membrane of the eye. It is continuous with the optic nerve and receives images of external objects and transmits visual impulses to the brain. Its outer surface is in contact with the choroid and the inner surface with the vitreous body. The outer-most layer is pigmented, whereas the inner nine layers are transparent. [NIH] Retinal: 1. Pertaining to the retina. 2. The aldehyde of retinol, derived by the oxidative enzymatic splitting of absorbed dietary carotene, and having vitamin A activity. In the retina, retinal combines with opsins to form visual pigments. One isomer, 11-cis retinal combines with opsin in the rods (scotopsin) to form rhodopsin, or visual purple. Another, all-trans retinal (trans-r.); visual yellow; xanthopsin) results from the bleaching of rhodopsin by light, in which the 11-cis form is converted to the all-trans form. Retinal also combines with opsins in the cones (photopsins) to form the three pigments responsible for colour vision. Called also retinal, and retinene1. [EU] Retinal Ganglion Cells: Cells of the innermost nuclear layer of the retina, the ganglion cell layer, which project axons through the optic nerve to the brain. They are quite variable in size and in the shapes of their dendritic arbors, which are generally confined to the inner plexiform layer. [NIH] 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] Retinitis Pigmentosa: Hereditary, progressive degeneration of the neuroepithelium of the retina characterized by night blindness and progressive contraction of the visual field. [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] Retrospective: Looking back at events that have already taken place. [NIH]
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Retrospective study: A study that looks backward in time, usually using medical records and interviews with patients who already have or had a disease. [NIH] 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] Rheology: The study of the deformation and flow of matter, usually liquids or fluids, and of the plastic flow of solids. The concept covers consistency, dilatancy, liquefaction, resistance to flow, shearing, thixotrophy, and viscosity. [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] Ribosome: A granule of protein and RNA, synthesized in the nucleolus and found in the cytoplasm of cells. Ribosomes are the main sites of protein synthesis. Messenger RNA attaches to them and there receives molecules of transfer RNA bearing amino acids. [NIH] Rigidity: Stiffness or inflexibility, chiefly that which is abnormal or morbid; rigor. [EU] Risk factor: A habit, trait, condition, or genetic alteration that increases a person's chance of developing a disease. [NIH] Ristocetin: An antibiotic mixture of two components, A and B, obtained from Nocardia lurida (or the same substance produced by any other means). It is no longer used clinically because of its toxicity. It causes platelet agglutination and blood coagulation and is used to assay those functions in vitro. [NIH] Rod: A reception for vision, located in the retina. [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] S Phase: Phase of the cell cycle following G1 and preceding G2 when the entire DNA content of the nucleus is replicated. It is achieved by bidirectional replication at multiple sites along each chromosome. [NIH] Saline: A solution of salt and water. [NIH] Saliva: The clear, viscous fluid secreted by the salivary glands and mucous glands of the mouth. It contains mucins, water, organic salts, and ptylin. [NIH] Salivary: The duct that convey saliva to the mouth. [NIH] Salivary glands: Glands in the mouth that produce saliva. [NIH] Schizoid: Having qualities resembling those found in greater degree in schizophrenics; a person of schizoid personality. [NIH] Schizophrenia: A mental disorder characterized by a special type of disintegration of the personality. [NIH] Schizotypal Personality Disorder: A personality disorder in which there are oddities of thought (magical thinking, paranoid ideation, suspiciousness), perception (illusions, depersonalization), speech (digressive, vague, overelaborate), and behavior (inappropriate
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affect in social interactions, frequently social isolation) that are not severe enough to characterize schizophrenia. [NIH] Scleroproteins: Simple proteins characterized by their insolubility and fibrous structure. Within the body, they perform a supportive or protective function. [NIH] 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] Scrapie: A fatal disease of the nervous system in sheep and goats, characterized by pruritus, debility, and locomotor incoordination. It is caused by proteinaceous infectious particles called prions. [NIH] Screening: Checking for disease when there are no symptoms. [NIH] Scrub Typhus: An acute infectious disease caused by Orientia tsutsugamushi. It is limited to eastern and southeastern Asia, India, northern Australia, and the adjacent islands. Characteristics include the formation of a primary cutaneous lesion at the site of the bite of an infected mite, fever lasting about two weeks, and a maculopapular rash. [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] Segmental: Describing or pertaining to a structure which is repeated in similar form in successive segments of an organism, or which is undergoing segmentation. [NIH] 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] Semicircular canal: Three long canals of the bony labyrinth of the ear, forming loops and opening into the vestibule by five openings. [NIH] Semisynthetic: Produced by chemical manipulation of naturally occurring substances. [EU] Senile: Relating or belonging to old age; characteristic of old age; resulting from infirmity of old age. [NIH] 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]
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Sequencing: The determination of the order of nucleotides in a DNA or RNA chain. [NIH] Sequester: A portion of dead bone which has become detached from the healthy bone tissue, as occurs in necrosis. [NIH] Serine: A non-essential amino acid occurring in natural form as the L-isomer. It is synthesized from glycine or threonine. It is involved in the biosynthesis of purines, pyrimidines, and other amino acids. [NIH] 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] Sexually Transmitted Diseases: Diseases due to or propagated by sexual contact. [NIH] Shock: The general bodily disturbance following a severe injury; an emotional or moral upset occasioned by some disturbing or unexpected experience; disruption of the circulation, which can upset all body functions: sometimes referred to as circulatory shock. [NIH]
Side effect: A consequence other than the one(s) for which an agent or measure is used, as the adverse effects produced by a drug, especially on a tissue or organ system other than the one sought to be benefited by its administration. [EU] 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] 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] Sisomicin: Antibiotic produced by Micromonospora inyoensis. It is closely related to gentamicin C1A, one of the components of the gentamicin complex (gentamicins). [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
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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] Smear Layer: Adherent debris produced when cutting the enamel or dentin in cavity preparation. It is about 1 micron thick and its composition reflects the underlying dentin, although different quantities and qualities of smear layer can be produced by the various instrumentation techniques. Its function is presumed to be protective, as it lowers dentin permeability. However, it masks the underlying dentin and interferes with attempts to bond dental material to the dentin. [NIH] Smooth muscle: Muscle that performs automatic tasks, such as constricting blood vessels. [NIH]
Social Environment: The aggregate of social and cultural institutions, forms, patterns, and processes that influence the life of an individual or community. [NIH] Sodium: An element that is a member of the alkali group of metals. It has the atomic symbol Na, atomic number 11, and atomic weight 23. With a valence of 1, it has a strong affinity for oxygen and other nonmetallic elements. Sodium provides the chief cation of the extracellular body fluids. Its salts are the most widely used in medicine. (From Dorland, 27th ed) Physiologically the sodium ion plays a major role in blood pressure regulation, maintenance of fluid volume, and electrolyte balance. [NIH] Soft tissue: Refers to muscle, fat, fibrous tissue, blood vessels, or other supporting tissue of the body. [NIH] Solid tumor: Cancer of body tissues other than blood, bone marrow, or the lymphatic system. [NIH] Solvent: 1. Dissolving; effecting a solution. 2. A liquid that dissolves or that is capable of dissolving; the component of a solution that is present in greater amount. [EU] 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] Spatial disorientation: Loss of orientation in space where person does not know which way is up. [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] 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] 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
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a disease. [EU] 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] 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] Splenic Vein: Vein formed by the union (at the hilus of the spleen) of several small veins from the stomach, pancreas, spleen and mesentery. [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] Spotting: A slight discharge of blood via the vagina, especially as a side-effect of oral contraceptives. [EU] Staphylococcal Infections: Infections with bacteria of the genus Staphylococcus. [NIH] Staphylococcus: A genus of gram-positive, facultatively anaerobic, coccoid bacteria. Its organisms occur singly, in pairs, and in tetrads and characteristically divide in more than one plane to form irregular clusters. Natural populations of Staphylococcus are membranes of warm-blooded animals. Some species are opportunistic pathogens of humans and animals. [NIH] Statistically significant: Describes a mathematical measure of difference between groups. The difference is said to be statistically significant if it is greater than what might be expected to happen by chance alone. [NIH] Stem cell transplantation: A method of replacing immature blood-forming cells that were destroyed by cancer treatment. The stem cells are given to the person after treatment to help the bone marrow recover and continue producing healthy blood cells. [NIH] Stem Cells: Relatively undifferentiated cells of the same lineage (family type) that retain the ability to divide and cycle throughout postnatal life to provide cells that can become specialized and take the place of those that die or are lost. [NIH] 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] Sternum: Breast bone. [NIH] Steroids: Drugs used to relieve swelling and inflammation. [NIH] Stillbirth: The birth of a dead fetus or baby. [NIH]
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Stimulus: That which can elicit or evoke action (response) in a muscle, nerve, gland or other excitable issue, or cause an augmenting action upon any function or metabolic process. [NIH] Stomach: An organ of digestion situated in the left upper quadrant of the abdomen between the termination of the esophagus and the beginning of the duodenum. [NIH] Stool: The waste matter discharged in a bowel movement; feces. [NIH] Strand: DNA normally exists in the bacterial nucleus in a helix, in which two strands are coiled together. [NIH] 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] 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] Stress Fibers: Bundles of actin filaments (microfilaments) and myosin-II that span across the cell attaching to the cell membrane at focal adhesions and to the network of intermediate filaments that surrounds the nucleus. [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] Stromal Cells: Connective tissue cells of an organ found in the loose connective tissue. These are most often associated with the uterine mucosa and the ovary as well as the hematopoietic system and elsewhere. [NIH] 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] Subiculum: A region of the hippocampus that projects to other areas of the brain. [NIH] Submaxillary: Four to six lymph glands, located between the lower jaw and the submandibular salivary gland. [NIH] Subspecies: A category intermediate in rank between species and variety, based on a smaller number of correlated characters than are used to differentiate species and generally conditioned by geographical and/or ecological occurrence. [NIH] Substance P: An eleven-amino acid neurotransmitter that appears in both the central and peripheral nervous systems. It is involved in transmission of pain, causes rapid contractions of the gastrointestinal smooth muscle, and modulates inflammatory and immune responses. [NIH]
Substrate: A substance upon which an enzyme acts. [EU]
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Subtrochanteric: Below a trochanter. [NIH] Sulfadiazine: A short-acting sulfonamide used in combination with pyrimethamine to treat toxoplasmosis in patients with acquired immunodeficiency syndrome and in newborns with congenital infections. [NIH] Sulfur: An element that is a member of the chalcogen family. It has an atomic symbol S, atomic number 16, and atomic weight 32.066. It is found in the amino acids cysteine and methionine. [NIH] Superoxide: Derivative of molecular oxygen that can damage cells. [NIH] Superoxide Dismutase: An oxidoreductase that catalyzes the reaction between superoxide anions and hydrogen to yield molecular oxygen and hydrogen peroxide. The enzyme protects the cell against dangerous levels of superoxide. EC 1.15.1.1. [NIH] Supplementation: Adding nutrients to the diet. [NIH] Suppositories: A small cone-shaped medicament having cocoa butter or gelatin at its basis and usually intended for the treatment of local conditions in the rectum. [NIH] Suppression: A conscious exclusion of disapproved desire contrary with repression, in which the process of exclusion is not conscious. [NIH] Suppressive: Tending to suppress : effecting suppression; specifically : serving to suppress activity, function, symptoms. [EU] 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] Synapses: Specialized junctions at which a neuron communicates with a target cell. At classical synapses, a neuron's presynaptic terminal releases a chemical transmitter stored in synaptic vesicles which diffuses across a narrow synaptic cleft and activates receptors on the postsynaptic membrane of the target cell. The target may be a dendrite, cell body, or axon of another neuron, or a specialized region of a muscle or secretory cell. Neurons may also communicate through direct electrical connections which are sometimes called electrical synapses; these are not included here but rather in gap junctions. [NIH] Synaptic: Pertaining to or affecting a synapse (= site of functional apposition between neurons, at which an impulse is transmitted from one neuron to another by electrical or chemical means); pertaining to synapsis (= pairing off in point-for-point association of homologous chromosomes from the male and female pronuclei during the early prophase of meiosis). [EU] Synaptic Vesicles: Membrane-bound compartments which contain transmitter molecules. Synaptic vesicles are concentrated at presynaptic terminals. They actively sequester transmitter molecules from the cytoplasm. In at least some synapses, transmitter release occurs by fusion of these vesicles with the presynaptic membrane, followed by exocytosis of their contents. [NIH]
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Synaptosomes: Pinched-off nerve endings and their contents of vesicles and cytoplasm together with the attached subsynaptic area of the membrane of the post-synaptic cell. They are largely artificial structures produced by fractionation after selective centrifugation of nervous tissue homogenates. [NIH] Synergistic: Acting together; enhancing the effect of another force or agent. [EU] Synovial: Of pertaining to, or secreting synovia. [EU] Systemic: Affecting the entire body. [NIH] Systolic: Indicating the maximum arterial pressure during contraction of the left ventricle of the heart. [EU] Tachycardia: Excessive rapidity in the action of the heart, usually with a heart rate above 100 beats per minute. [NIH] Tachypnea: Rapid breathing. [NIH] Tamoxifen: A first generation selective estrogen receptor modulator (SERM). It acts as an agonist for bone tissue and cholesterol metabolism but is an estrogen antagonist in mammary and uterine. [NIH] Tamponade: The inserting of a tampon; a dressing is inserted firmly into a wound or body cavity, as the nose, uterus or vagina, principally for stopping hemorrhage. [NIH] Telophase: The final phase of cell division, in which two daughter nuclei are formed, the cytoplasm divides, and the chromosomes lose their distinctness and are transformed into chromatin networks. [NIH] Temporal: One of the two irregular bones forming part of the lateral surfaces and base of the skull, and containing the organs of hearing. [NIH] Temporal Lobe: Lower lateral part of the cerebral hemisphere. [NIH] Testosterone: A hormone that promotes the development and maintenance of male sex characteristics. [NIH] Tetracycline: An antibiotic originally produced by Streptomyces viridifaciens, but used mostly in synthetic form. It is an inhibitor of aminoacyl-tRNA binding during protein synthesis. [NIH] Tetracycline Resistance: Nonsusceptibility of a microbe (usually a bacterium) to the action of tetracycline, which binds to the 30S ribosomal subunit and prevents the normal binding of aminoacyl-tRNA. [NIH] Thalamus: Paired bodies containing mostly gray substance and forming part of the lateral wall of the third ventricle of the brain. The thalamus represents the major portion of the diencephalon and is commonly divided into cellular aggregates known as nuclear groups. [NIH]
Theophylline: Alkaloid obtained from Thea sinensis (tea) and others. It stimulates the heart and central nervous system, dilates bronchi and blood vessels, and causes diuresis. The drug is used mainly in bronchial asthma and for myocardial stimulation. Among its more prominent cellular effects are inhibition of cyclic nucleotide phosphodiesterases and antagonism of adenosine receptors. [NIH] Therapeutics: The branch of medicine which is concerned with the treatment of diseases, palliative or curative. [NIH] Thermal: Pertaining to or characterized by heat. [EU] Thigh: A leg; in anatomy, any elongated process or part of a structure more or less comparable to a leg. [NIH]
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Thorax: A part of the trunk between the neck and the abdomen; the chest. [NIH] Threonine: An essential amino acid occurring naturally in the L-form, which is the active form. It is found in eggs, milk, gelatin, and other proteins. [NIH] Threshold: For a specified sensory modality (e. g. light, sound, vibration), the lowest level (absolute threshold) or smallest difference (difference threshold, difference limen) or intensity of the stimulus discernible in prescribed conditions of stimulation. [NIH] Thrombin: An enzyme formed from prothrombin that converts fibrinogen to fibrin. (Dorland, 27th ed) EC 3.4.21.5. [NIH] Thrombolytic: 1. Dissolving or splitting up a thrombus. 2. A thrombolytic agent. [EU] Thrombomodulin: A cell surface glycoprotein of endothelial cells that binds thrombin and serves as a cofactor in the activation of protein C and its regulation of blood coagulation. [NIH]
Thrombophlebitis: Inflammation of a vein associated with thrombus formation. [NIH] Thrombosis: The formation or presence of a blood clot inside a blood vessel. [NIH] Thrombus: An aggregation of blood factors, primarily platelets and fibrin with entrapment of cellular elements, frequently causing vascular obstruction at the point of its formation. Some authorities thus differentiate thrombus formation from simple coagulation or clot formation. [EU] 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 Neoplasms: Tumors or cancer of the thyroid gland. [NIH] Ticks: Blood-sucking arachnids of the order Acarina. [NIH] Tissue: A group or layer of cells that are alike in type and work together to perform a specific function. [NIH] Tocolytic Agents: Drugs that prevent preterm labor and immature birth by suppressing uterine contractions. Agents used to delay premature uterine activity include magnesium sulfate, beta-mimetics, oxytocin antagonists, calcium channel inhibitors, and adrenergic beta-receptor agonists. The use of intravenous alcohol as a tocolytic is now obsolete. [NIH] Tolerance: 1. The ability to endure unusually large doses of a drug or toxin. 2. Acquired drug tolerance; a decreasing response to repeated constant doses of a drug or the need for increasing doses to maintain a constant response. [EU] Tomography: Imaging methods that result in sharp images of objects located on a chosen plane and blurred images located above or below the plane. [NIH] Tooth Loss: The failure to retain teeth as a result of disease or injury. [NIH] Topical: On the surface of the body. [NIH] Toxic: Having to do with poison or something harmful to the body. Toxic substances usually cause unwanted side effects. [NIH] Toxicity: The quality of being poisonous, especially the degree of virulence of a toxic microbe or of a poison. [EU] Toxicology: The science concerned with the detection, chemical composition, and
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pharmacologic action of toxic substances or poisons and the treatment and prevention of toxic manifestations. [NIH] Toxins: Specific, characterizable, poisonous chemicals, often proteins, with specific biological properties, including immunogenicity, produced by microbes, higher plants, or animals. [NIH] Toxoplasmosis: The acquired form of infection by Toxoplasma gondii in animals and man. [NIH]
Trace element: Substance or element essential to plant or animal life, but present in extremely small amounts. [NIH] Trachea: The cartilaginous and membranous tube descending from the larynx and branching into the right and left main bronchi. [NIH] Trans-Activators: Diffusible gene products that act on homologous or heterologous molecules of viral or cellular DNA to regulate the expression of proteins. [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] Transdermal: Entering through the dermis, or skin, as in administration of a drug applied to the skin in ointment or patch form. [EU] Transduction: The transfer of genes from one cell to another by means of a viral (in the case of bacteria, a bacteriophage) vector or a vector which is similar to a virus particle (pseudovirion). [NIH] Transfection: The uptake of naked or purified DNA into cells, usually eukaryotic. It is analogous to bacterial transformation. [NIH] Transfer Factor: Factor derived from leukocyte lysates of immune donors which can transfer both local and systemic cellular immunity to nonimmune recipients. [NIH] Transferases: Transferases are enzymes transferring a group, for example, the methyl group or a glycosyl group, from one compound (generally regarded as donor) to another compound (generally regarded as acceptor). The classification is based on the scheme "donor:acceptor group transferase". (Enzyme Nomenclature, 1992) EC 2. [NIH] 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]
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]
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Transmitter: A chemical substance which effects the passage of nerve impulses from one cell to the other at the synapse. [NIH] Transplantation: Transference of a tissue or organ, alive or dead, within an individual, between individuals of the same species, or between individuals of different species. [NIH] Trauma: Any injury, wound, or shock, must frequently physical or structural shock, producing a disturbance. [NIH] Trees: Woody, usually tall, perennial higher plants (Angiosperms, Gymnosperms, and some Pterophyta) having usually a main stem and numerous branches. [NIH] 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] Trisomy: The possession of a third chromosome of any one type in an otherwise diploid cell. [NIH]
Tropical Medicine: The branch of medicine concerned with diseases, mainly of parasitic origin, common in tropical and subtropical regions. [NIH] Tropoelastin: A salt-soluble precursor of elastin. Lysyl oxidase is instrumental in converting it to elastin in connective tissue. [NIH] Trypsin: A serine endopeptidase that is formed from trypsinogen in the pancreas. It is converted into its active form by enteropeptidase in the small intestine. It catalyzes hydrolysis of the carboxyl group of either arginine or lysine. EC 3.4.21.4. [NIH] Tryptophan: An essential amino acid that is necessary for normal growth in infants and for nitrogen balance in adults. It is a precursor serotonin and niacin. [NIH] Tubercle: A rounded elevation on a bone or other structure. [NIH] Tuberculosis: Any of the infectious diseases of man and other animals caused by species of Mycobacterium. [NIH] Tuberous Sclerosis: A rare congenital disease in which the essential pathology is the appearance of multiple tumors in the cerebrum and in other organs, such as the heart or kidneys. [NIH] Tumor Necrosis Factor: Serum glycoprotein produced by activated macrophages and other mammalian mononuclear leukocytes which has necrotizing activity against tumor cell lines and increases ability to reject tumor transplants. It mimics the action of endotoxin but differs from it. It has a molecular weight of less than 70,000 kDa. [NIH] Tumor suppressor gene: Genes in the body that can suppress or block the development of cancer. [NIH] Tumour: 1. Swelling, one of the cardinal signs of inflammations; morbid enlargement. 2. A new growth of tissue in which the multiplication of cells is uncontrolled and progressive; called also neoplasm. [EU] Type 2 diabetes: Usually characterized by a gradual onset with minimal or no symptoms of metabolic disturbance and no requirement for exogenous insulin. The peak age of onset is 50
256 Doxycycline
to 60 years. Obesity and possibly a genetic factor are usually present. [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] Unconscious: Experience which was once conscious, but was subsequently rejected, as the "personal unconscious". [NIH] Uremia: The illness associated with the buildup of urea in the blood because the kidneys are not working effectively. Symptoms include nausea, vomiting, loss of appetite, weakness, and mental confusion. [NIH] Ureters: Tubes that carry urine from the kidneys to the bladder. [NIH] Urethra: The tube through which urine leaves the body. It empties urine from the bladder. [NIH]
Urethritis: Inflammation of the urethra. [EU] Uricosuric: 1. Pertaining to, characterized by, or promoting uricosuria (= the excretion of uric acid in the urine). 2. An agent that promotes uricosuria. [EU] Urinary: Having to do with urine or the organs of the body that produce and get rid of urine. [NIH] Urinary tract: The organs of the body that produce and discharge urine. These include the kidneys, ureters, bladder, and urethra. [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] Urokinase: A drug that dissolves blood clots or prevents them from forming. [NIH] Urothelium: The epithelial lining of the urinary tract. [NIH] Uterine Contraction: Contraction of the uterine muscle. [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] 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] Vancomycin: Antibacterial obtained from Streptomyces orientalis. It is a glycopeptide related to ristocetin that inhibits bacterial cell wall assembly and is toxic to kidneys and the inner ear. [NIH] 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
Dictionary 257
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] Vasodilation: Physiological dilation of the blood vessels without anatomic change. For dilation with anatomic change, dilatation, pathologic or aneurysm (or specific aneurysm) is used. [NIH] Vasodilator: An agent that widens blood vessels. [NIH] Vector: Plasmid or other self-replicating DNA molecule that transfers DNA between cells in nature or in recombinant DNA technology. [NIH] Vein: Vessel-carrying blood from various parts of the body to the heart. [NIH] Venous: Of or pertaining to the veins. [EU] 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] Ventral: 1. Pertaining to the belly or to any venter. 2. Denoting a position more toward the belly surface than some other object of reference; same as anterior in human anatomy. [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] 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] 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] Vestibule: A small, oval, bony chamber of the labyrinth. The vestibule contains the utricle and saccule, organs which are part of the balancing apparatus of the ear. [NIH] Veterinary Medicine: The medical science concerned with the prevention, diagnosis, and treatment of diseases in animals. [NIH] Vibrio: A genus of Vibrionaceae, made up of short, slightly curved, motile, gram-negative rods. Various species produce cholera and other gastrointestinal disorders as well as abortion in sheep and cattle. [NIH] Vibrio cholerae: The etiologic agent of cholera. [NIH] Vinca Alkaloids: A class of alkaloids from the genus of apocyanaceous woody herbs including periwinkles. They are some of the most useful antineoplastic agents. [NIH] Vincristine: An anticancer drug that belongs to the family of plant drugs called vinca alkaloids. [NIH] Viral: Pertaining to, caused by, or of the nature of virus. [EU] Viral vector: A type of virus used in cancer therapy. The virus is changed in the laboratory and cannot cause disease. Viral vectors produce tumor antigens (proteins found on a tumor
258 Doxycycline
cell) and can stimulate an antitumor immune response in the body. Viral vectors may also be used to carry genes that can change cancer cells back to normal cells. [NIH] Virulence: The degree of pathogenicity within a group or species of microorganisms or viruses as indicated by case fatality rates and/or the ability of the organism to invade the tissues of the host. [NIH] 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] Viscera: Any of the large interior organs in any one of the three great cavities of the body, especially in the abdomen. [NIH] Viscosity: A physical property of fluids that determines the internal resistance to shear forces. [EU] Visual field: The entire area that can be seen when the eye is forward, including peripheral vision. [NIH] Vitreous Body: The transparent, semigelatinous substance that fills the cavity behind the crystalline lens of the eye and in front of the retina. It is contained in a thin hyoid membrane and forms about four fifths of the optic globe. [NIH] Vitro: Descriptive of an event or enzyme reaction under experimental investigation occurring outside a living organism. Parts of an organism or microorganism are used together with artificial substrates and/or conditions. [NIH] Vivo: Outside of or removed from the body of a living organism. [NIH] Volition: Voluntary activity without external compulsion. [NIH] Volvulus: A twisting of the stomach or large intestine. May be caused by the stomach being in the wrong position, a foreign substance, or abnormal joining of one part of the stomach or intestine to another. Volvulus can lead to blockage, perforation, peritonitis, and poor blood flow. [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] Withdrawal: 1. A pathological retreat from interpersonal contact and social involvement, as may occur in schizophrenia, depression, or schizoid avoidant and schizotypal personality disorders. 2. (DSM III-R) A substance-specific organic brain syndrome that follows the cessation of use or reduction in intake of a psychoactive substance that had been regularly used to induce a state of intoxication. [EU] Wound Healing: Restoration of integrity to traumatized tissue. [NIH] 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
Dictionary 259
treat cancer. [NIH] Yeasts: A general term for single-celled rounded fungi that reproduce by budding. Brewers' and bakers' yeasts are Saccharomyces cerevisiae; therapeutic dried yeast is dried yeast. [NIH] 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]
261
INDEX A Abdomen, 162, 175, 185, 201, 208, 216, 219, 221, 223, 233, 249, 250, 253, 258 Abdominal, 7, 35, 37, 42, 75, 92, 94, 103, 148, 175, 196, 231, 233 Abdominal Pain, 7, 175, 233 Aberrant, 10, 39, 175 Ablate, 36, 175, 198 Ablation, 29, 175 Acceptor, 175, 219, 231, 254 Acetaldehyde, 175, 197 Acetylcholine, 23, 175, 189, 228 Acne, 68, 81, 175 Acne Vulgaris, 68, 175 Actin, 175, 223, 226, 227, 250 Acyclovir, 158, 175 Acyl, 175, 222 Adaptability, 175, 188 Adaptation, 175, 228, 236 Adenocarcinomas, 34, 175 Adenoma, 57, 176 Adenosine, 176, 234, 252 Adenovirus, 12, 26, 48, 63, 66, 86, 107, 176 Adenylate Cyclase, 43, 176 Adhesions, 176 Adipose Tissue, 176, 231 Adjuvant, 19, 81, 107, 114, 115, 148, 176, 206 Adjuvant Therapy, 148, 176 Adrenal Cortex, 176, 239, 243 Adrenergic, 24, 176, 177, 197, 201, 239, 241, 251, 253 Adrenergic Agonists, 24, 176 Adverse Effect, 23, 176, 247 Aerobic, 176, 224, 249 Aerosol, 176, 238 Aetiology, 68, 176 Afferent, 43, 176, 203, 238 Affinity, 8, 27, 39, 137, 176, 177, 182, 248 Agar, 176, 235 Age of Onset, 177, 255 Agonist, 177, 197, 226, 242, 252 Airway, 18, 60, 177 Aldehyde Dehydrogenase, 177, 197 Algorithms, 177, 184 Alimentary, 177, 232, 233 Alkaline, 54, 128, 177, 186 Alkaline Phosphatase, 54, 177
Alkaloid, 177, 241, 252 Allergen, 60, 177 Alpha 1-Antitrypsin, 98, 177 Alpha 1-Antitrypsin Deficiency, 98, 177 Alpha Particles, 177, 242 Alpha-helix, 177, 217 Alprenolol, 136, 177 Alternative medicine, 149, 177 Alternative Splicing, 36, 177, 240 Alveolar Bone Loss, 33, 177 Alveolar Process, 178, 244 Amebiasis, 178, 223 Amino Acid Sequence, 178, 180, 202, 220 Amino Acids, 22, 178, 201, 228, 233, 237, 240, 245, 247, 251, 254 Amoxicillin, 20, 98, 112, 142, 178 Ampicillin, 64, 141, 178 Amplification, 41, 135, 178 Ampulla, 178, 200, 203 Amygdala, 55, 178, 218 Amyloid, 25, 52, 178 Anaerobic, 100, 178, 209, 226, 249 Anaesthesia, 178, 213 Anal, 69, 162, 178 Analgesic, 19, 178, 212, 241 Analog, 54, 139, 175, 178, 190 Analogous, 178, 237, 254 Anaphylatoxins, 178, 192 Anaplasia, 178 Anatomical, 127, 179, 182, 199, 213, 246 Anemia, 59, 179, 221 Anesthesia, 177, 179, 239 Aneuploidy, 41, 179 Aneurysm, 36, 42, 75, 179, 181, 257 Angina, 179, 239 Angina Pectoris, 179, 239 Anginal, 177, 179 Angiogenesis, 15, 50, 90, 179, 221 Angiopathy, 26, 52, 179 Animal model, 18, 19, 21, 30, 35, 45, 46, 55, 59, 179 Anions, 179, 216, 238, 247, 251 Anisotropy, 179, 204 Annealing, 179, 237 Antagonism, 179, 252 Anthrax, 148, 162, 164, 179 Antibacterial, 7, 86, 106, 125, 133, 143, 180, 189, 190, 204, 229, 239, 248, 256
262 Doxycycline
Antibodies, 23, 126, 180, 209, 212, 213, 220, 235 Antibody, 61, 93, 147, 176, 180, 191, 200, 204, 209, 211, 213, 214, 217, 222, 224, 242, 248 Anticoagulant, 107, 180, 239, 258 Antigen, 8, 18, 21, 46, 126, 176, 180, 192, 196, 200, 204, 211, 212, 213, 214, 215, 222, 239 Antigen-Antibody Complex, 180, 192 Antigen-presenting cell, 180, 196 Antihypertensive, 46, 177, 180 Anti-infective, 124, 142, 180, 189, 211, 216 Anti-inflammatory, 16, 18, 63, 120, 124, 136, 163, 180, 212 Antimetabolite, 175, 180 Antineoplastic, 180, 184, 257 Antioxidant, 44, 180, 181, 231 Antipyretic, 180, 241 Antiseptic, 180, 238 Antiviral, 25, 158, 175, 180, 215 Anus, 163, 178, 180, 185, 236 Anxiety, 181, 239 Aorta, 37, 181, 257 Aortic Aneurysm, 35, 37, 42, 75, 92, 94, 103, 181 Aponeurosis, 181, 205 Apoptosis, 10, 11, 13, 16, 33, 34, 76, 85, 113, 135, 181, 187 Aqueous, 26, 127, 128, 132, 181, 183, 187, 195, 211, 219 Arachidonate 12-Lipoxygenase, 181, 219 Arachidonate 15-Lipoxygenase, 181, 219 Arachidonate Lipoxygenases, 181, 219 Arginine, 178, 181, 228, 255 Arterial, 48, 78, 181, 186, 193, 212, 240, 252 Arteries, 179, 181, 184, 193, 194, 217, 223, 226, 241 Arterioles, 181, 184, 186 Articular, 181, 230 Asbestos, 181, 221, 223 Ascites, 145, 181 Ascorbic Acid, 136, 181, 212 Aseptic, 181, 249 Aspartate, 13, 181 Assay, 17, 35, 47, 50, 52, 61, 64, 181, 213, 245 Astrocytes, 35, 50, 54, 182, 215 Asymptomatic, 92, 178, 182 Atopic, 60, 182 Atrial, 182, 193, 255, 258 Atrial Fibrillation, 182, 258
Atrioventricular, 182, 193 Atrium, 182, 193, 255, 257 Atrophy, 182, 227 Attenuated, 17, 126, 139, 140, 182 Auditory, 182, 209, 238 Autoimmune disease, 33, 182, 225 Autonomic, 175, 182, 228, 233 Axons, 182, 196, 230, 244 Azithromycin, 7, 9, 21, 62, 63, 65, 66, 67, 68, 69, 71, 73, 74, 80, 84, 87, 96, 97, 106, 163, 182 B Babesiosis, 182, 241 Bacillus, 51, 63, 179, 182 Bacteremia, 94, 182, 222 Bacteria, 22, 30, 46, 115, 124, 132, 134, 137, 175, 180, 182, 183, 184, 186, 199, 200, 202, 203, 208, 211, 218, 219, 223, 226, 229, 235, 242, 243, 248, 249, 250, 254, 256 Bacterial Infections, 132, 162, 182, 188, 218 Bactericidal, 183, 202, 229 Bacteriophage, 183, 235, 254, 258 Bacteriostatic, 132, 183, 201 Bacterium, 183, 240, 252 Basal Ganglia, 183, 205, 218, 229 Base, 8, 106, 128, 183, 196, 201, 202, 217, 237, 252 Basement Membrane, 183, 203, 218 Basophils, 27, 183, 208, 218 Benign, 11, 41, 77, 176, 183, 205, 209, 223, 227, 242 Beta-Galactosidase, 29, 34, 183 Beta-pleated, 178, 183 Beta-Thromboglobulin, 183, 215 Bilateral, 183, 244 Bile, 183, 189, 205, 211, 219 Bile Ducts, 183, 189 Binding Sites, 6, 49, 183 Bioassay, 70, 183 Biochemical, 7, 26, 33, 36, 40, 46, 51, 53, 55, 76, 177, 180, 183, 197, 204, 208, 230 Biofilms, 20, 98, 184 Biological response modifier, 184, 215 Biological therapy, 184, 209 Biopsy, 3, 8, 184, 233 Biopsy specimen, 3, 184 Biosynthesis, 79, 184, 247 Biotechnology, 61, 64, 66, 141, 149, 157, 184 Bladder, 43, 129, 184, 195, 225, 239, 256 Bleomycin, 32, 92, 95, 149, 184 Blood Coagulation, 184, 186, 245, 253
Index 263
Blood Glucose, 184, 209, 214 Blood pressure, 45, 180, 184, 186, 187, 212, 224, 241, 248 Blood vessel, 15, 179, 184, 187, 189, 193, 199, 200, 207, 217, 220, 223, 234, 248, 250, 252, 253, 257 Blood Volume, 184, 238 Blood-Brain Barrier, 184, 199 Blot, 14, 40, 184 Body Fluids, 184, 198, 248 Body Mass Index, 184, 231 Bone Density, 119, 185 Bone Marrow, 47, 48, 93, 185, 201, 213, 220, 222, 248, 249, 250 Bone Marrow Cells, 48, 185, 222 Bone Marrow Transplantation, 47, 48, 93, 185 Bone Resorption, 33, 77, 185, 233 Bowel, 124, 178, 185, 196, 216, 250 Bowel Movement, 185, 196, 250 Brachytherapy, 185, 215, 217, 242 Bradykinin, 185, 228, 235 Brain Stem, 185, 227 Branch, 171, 185, 220, 232, 241, 248, 251, 252, 255 Breakdown, 15, 26, 33, 134, 185, 196, 206, 230 Broad-spectrum, 127, 178, 185, 187, 207, 229 Bronchi, 185, 201, 252, 254 Bronchial, 185, 252 Bronchiectasis, 71, 185 Bronchitis, 137, 185, 190 Bronchoalveolar Lavage, 60, 185 Bronchoconstriction, 136, 185 Bronchopulmonary, 50, 185 Bronchopulmonary Dysplasia, 50, 185 Bronchus, 185, 186 Brucellosis, 62, 64, 70, 102, 186 Buccal, 136, 186, 220 Bullous, 111, 186 C Calcium, 11, 109, 110, 136, 181, 186, 190, 191, 202, 212, 221, 247, 253 Callus, 186, 199 Candidiasis, 40, 186 Candidosis, 186 Capillary, 113, 185, 186, 257 Caprolactam, 132, 186 Capsules, 3, 186, 197, 206 Captopril, 136, 186 Carbohydrate, 186, 208, 237
Carboxy, 28, 186 Carcinogen, 11, 186, 223 Carcinogenesis, 34, 186, 189 Carcinogenic, 186, 214, 230, 239 Carcinoma, 62, 76, 82, 106, 186, 187 Cardiac, 30, 45, 92, 182, 187, 190, 193, 199, 201, 202, 226, 241 Cardioselective, 187, 239 Cardiovascular, 45, 75, 92, 94, 103, 187 Cardiovascular disease, 45, 187 Carotene, 187, 244 Case report, 94, 108, 187, 190 Caspase, 13, 76, 187 Catecholamine, 187, 197 Cathepsins, 9, 187 Cathode, 187, 199 Cations, 116, 187, 216 Caudal, 187, 196, 229, 237 Caudate Nucleus, 187, 229 Causal, 11, 187, 240 Cause of Death, 128, 187 Cefaclor, 139, 187 Cefoxitin, 31, 42, 187 Ceftriaxone, 8, 62, 69, 90, 119, 120, 187 Cefuroxime, 61, 187 Cell Adhesion, 187, 215 Cell Cycle, 41, 51, 57, 187, 194, 239, 245 Cell Death, 13, 15, 39, 44, 48, 55, 135, 181, 188, 227 Cell Differentiation, 40, 46, 51, 188, 247 Cell Division, 182, 188, 209, 216, 222, 224, 235, 246, 252 Cell membrane, 188, 196, 206, 234, 250 Cell motility, 37, 188 Cell proliferation, 6, 32, 50, 188, 247 Cell Respiration, 188, 224, 244 Cell Size, 188, 204 Cell Survival, 6, 188, 209 Cell Transplantation, 54, 188 Cellulose, 188, 205, 235 Central Nervous System, 8, 30, 43, 53, 54, 175, 188, 205, 209, 211, 225, 230, 252 Central Nervous System Infections, 188, 209, 211 Centrifugation, 188, 252 Centrosome, 41, 188, 224 Cephalexin, 187, 188 Cerebral, 21, 52, 93, 183, 184, 185, 188, 189, 201, 204, 205, 211, 221, 227, 252 Cerebrospinal, 61, 72, 189, 211 Cerebrospinal fluid, 61, 72, 189, 211 Cerebrovascular, 52, 187, 189
264 Doxycycline
Cerebrum, 188, 189, 255 Cervical, 21, 162, 189 Cervix, 21, 163, 189 Character, 179, 189, 195 Chemokines, 22, 30, 34, 35, 189 Chemopreventive, 16, 57, 189 Chemotactic Factors, 189, 192 Chemotherapy, 65, 66, 68, 71, 72, 76, 80, 82, 84, 88, 90, 94, 99, 100, 102, 103, 112, 114, 132, 139, 176, 189 Chlamydia, 21, 63, 67, 72, 74, 80, 84, 87, 100, 162, 189, 230, 240 Chlorhexidine, 108, 143, 189 Chlortetracycline, 69, 132, 189 Cholangiography, 102, 189 Cholera, 93, 189, 257 Cholesterol, 48, 58, 183, 189, 194, 222, 242, 252 Choline, 23, 189 Cholinergic, 23, 189 Chorioretinitis, 189, 244 Choroid, 189, 190, 244 Chromatin, 40, 47, 181, 190, 200, 252 Chromosomal, 41, 54, 178, 179, 190, 223, 235, 245 Chromosome, 41, 55, 179, 190, 209, 218, 223, 225, 240, 245, 246, 255 Chronic Disease, 26, 190 Chronic Obstructive Pulmonary Disease, 137, 190 Chronic renal, 56, 59, 190, 237 Ciliary, 55, 190, 225 Ciliary Neurotrophic Factor, 55, 190 Cinchona, 190, 241 Ciprofloxacin, 51, 63, 66, 70, 87, 90, 93, 164, 190 CIS, 190, 244 Citric Acid, 99, 190 Citrus, 181, 190 Clavulanic Acid, 142, 190 Clear cell carcinoma, 190, 196 Clindamycin, 90, 142, 190 Clinical Medicine, 76, 84, 85, 114, 190, 238 Clinical study, 190, 193 Clinical trial, 4, 5, 6, 9, 16, 20, 32, 39, 59, 91, 119, 121, 143, 157, 190, 191, 193, 198, 225, 242 Clone, 41, 50, 54, 191 Cloning, 17, 184, 191 Cloxacillin, 141, 191 Coagulation, 27, 184, 191, 210, 235, 253, 258
Cochlea, 191, 214 Coenzyme, 115, 158, 181, 191, 204 Cofactor, 191, 228, 240, 253 Collagen, 7, 33, 37, 79, 133, 163, 183, 191, 203, 204, 206, 216, 221, 236, 239 Collagenases, 33, 73, 106, 129, 191 Collapse, 185, 191 Colloidal, 191, 199, 202, 247 Combinatorial, 47, 191 Complement, 12, 178, 191, 192, 206, 215, 221, 235 Complementary and alternative medicine, 111, 117, 192 Complementary medicine, 111, 192 Computational Biology, 157, 192 Conception, 192, 193, 204, 249 Condoms, 163, 192 Cone, 192, 235, 251 Congenita, 192, 241 Congestion, 192, 201 Conjunctiva, 192, 214, 219 Conjunctivitis, 68, 162, 192 Connective Tissue, 42, 134, 181, 185, 191, 192, 204, 205, 206, 220, 223, 240, 245, 250, 255 Connective Tissue Cells, 192 Consciousness, 178, 192, 195, 197 Constitutional, 193, 244 Constriction, 136, 193, 217, 240 Consumption, 54, 193, 244 Continuous infusion, 103, 193 Contraception, 19, 193 Contraceptive, 19, 193 Contractility, 24, 193 Contraindications, ii, 193 Contralateral, 19, 20, 193, 230 Control group, 5, 193, 238 Controlled clinical trial, 6, 18, 193 Controlled study, 20, 193 Coordination, 193, 225 Cor, 9, 193 Cornea, 9, 193, 217, 250 Corneal Ulcer, 133, 193 Corneum, 193, 201 Coronary, 100, 179, 187, 193, 194, 223, 226 Coronary heart disease, 100, 187, 193 Coronary Thrombosis, 194, 223, 226 Corpus, 194, 232, 239 Corpus Luteum, 194, 239 Cortex, 24, 194, 200, 204, 227, 238 Cortical, 53, 194, 238 Corticosteroids, 102, 194
Index 265
Coumarin, 107, 194 Cranial, 194, 202, 203, 209, 216, 230, 232, 233 Craniocerebral Trauma, 194, 209, 211 Creatine, 14, 194 Creatine Kinase, 14, 194 Creatinine, 194 Crossing-over, 194, 243 Cryptosporidiosis, 182, 194 Cultured cells, 21, 36, 194 Curative, 9, 194, 252 Curettage, 58, 194, 245 Curette, 194 Cutaneous, 72, 82, 102, 180, 186, 194, 220, 235, 246, 256 Cyclic, 99, 176, 186, 194, 209, 228, 234, 252 Cyclin, 51, 194 Cysteine, 44, 129, 189, 195, 197, 200, 251 Cystine, 195, 197 Cystitis, 43, 195 Cytokine, 8, 21, 26, 27, 30, 35, 55, 60, 195, 215, 233 Cytoplasm, 181, 183, 188, 195, 200, 208, 227, 245, 251, 252 Cytoskeleton, 195, 215, 224 Cytotoxic, 60, 126, 195, 220, 242, 247 D Databases, Bibliographic, 157, 195 Decubitus, 139, 195 Decubitus Ulcer, 139, 195 Defense Mechanisms, 195, 215 Degenerative, 12, 37, 42, 195, 210, 230, 244 Dehydration, 189, 195 Dehydroepiandrosterone, 163, 195 Deletion, 38, 56, 181, 195 Demeclocycline, 69, 195 Dementia, 13, 53, 195, 227 Denaturation, 195, 237 Dendrites, 195, 196, 228 Dendritic, 34, 195, 196, 222, 244 Dendritic cell, 34, 196 Density, 27, 32, 53, 185, 188, 196, 204, 230 Dentate Gyrus, 196, 210 Dentin Permeability, 196, 248 Depolarization, 48, 196, 247 Depressive Disorder, 196, 219 Dermal, 84, 196 DES, 13, 106, 107, 178, 196 Diabetes Mellitus, 26, 58, 115, 196, 207, 209 Diagnostic procedure, 123, 149, 196 Diaphragm, 196, 236
Diarrhea, 7, 178, 194, 196 Diastolic, 196, 212 Diencephalon, 196, 227, 238, 252 Diffusion, 196, 214 Digestion, 177, 183, 185, 196, 216, 219, 233, 250 Digestive system, 122, 196 Dihydrotestosterone, 196, 243 Dilatation, 179, 185, 196, 257 Dimerization, 27, 46, 137, 196 Diploid, 179, 196, 225, 235, 255 Disease Progression, 4, 5, 37, 197 Disinfectant, 189, 197, 202 Dissociation, 176, 197 Distal, 49, 56, 197, 240 Disulfiram, 158, 197 Disulphides, 197 Dithiothreitol, 44, 197 Diuresis, 197, 252 Dizziness, 7, 197 Dopamine, 54, 59, 197, 234 Dorsal, 43, 55, 197, 237 Dorsum, 197, 205 Dosage Forms, 133, 136, 138, 197 Dose-dependent, 59, 73, 198 Double-blinded, 97, 198 Drive, ii, vi, 8, 18, 32, 53, 105, 142, 198 Drug Interactions, 152, 198 Drug Tolerance, 198, 253 Duct, 178, 198, 202, 231, 245 Duodenum, 183, 198, 200, 250 Dura mater, 198, 222, 231 Dyes, 178, 183, 198, 204 E Ectopic, 6, 31, 33, 198 Ectopic Pregnancy, 31, 198 Edema, 198, 216 Effector, 30, 41, 56, 175, 191, 198, 228, 234 Effector cell, 56, 198, 228 Elastin, 37, 191, 198, 203, 255 Elective, 38, 198 Electrocoagulation, 191, 198 Electrolysis, 179, 187, 198 Electrolyte, 10, 198, 237, 248 Electron Spin Resonance Spectroscopy, 38, 199 Electrons, 180, 183, 187, 199, 216, 231, 242 Electrophoresis, 113, 199 Emboli, 199, 258 Embolism, 199, 241, 258 Embolization, 199, 258 Embryo, 51, 188, 199, 213, 237
266 Doxycycline
Embryogenesis, 53, 76, 199 Emepronium, 129, 136, 199 Emollient, 199, 229 Emphysema, 41, 137, 177, 190, 199 Enamel, 199, 217, 248 Encapsulated, 73, 80, 199, 219 Encephalopathy, 43, 199 Endemic, 13, 93, 108, 189, 199, 221, 249 Endocarditis, 73, 102, 147, 186, 199 Endocardium, 199, 200 Endometrial, 19, 200 Endometrium, 15, 19, 200, 222 Endopeptidases, 187, 200, 233 Endoscope, 200 Endoscopic, 102, 200 Endoscopy, 3, 102, 200 Endothelial cell, 84, 87, 90, 184, 200, 215, 253 Endothelium, 200, 228, 236 Endothelium-derived, 200, 228 Endotoxin, 200, 255 End-stage renal, 190, 200, 237 Enhancer, 10, 13, 40, 47, 56, 200, 244 Entorhinal Cortex, 200, 210 Environmental Exposure, 200, 230 Environmental Health, 156, 158, 200 Enzymatic, 44, 186, 187, 192, 200, 237, 244 Enzyme, 6, 18, 38, 44, 66, 81, 97, 112, 129, 176, 177, 181, 187, 191, 198, 200, 207, 209, 211, 217, 219, 228, 234, 235, 237, 239, 240, 243, 247, 250, 251, 253, 254, 258, 259 Enzyme-Linked Immunosorbent Assay, 18, 200 Eosinophilic, 60, 200 Eosinophils, 200, 208, 218 Epidemic, 31, 201, 249 Epidemiological, 58, 201 Epidermal, 10, 37, 69, 201, 217, 222 Epidermal Growth Factor, 37, 201 Epidermis, 10, 193, 201, 211, 212, 217, 238, 241 Epigastric, 201, 231 Epinephrine, 176, 197, 201, 228, 256 Epistaxis, 201, 240 Epithelial, 10, 11, 17, 21, 28, 32, 39, 40, 49, 51, 56, 89, 136, 175, 176, 193, 201, 215, 218, 233, 256 Epithelial Cells, 11, 17, 21, 39, 40, 51, 56, 89, 175, 201, 215, 218 Epithelium, 32, 34, 49, 76, 183, 200, 201, 216
Erectile, 201, 232 Erythema, 61, 71, 201 Erythrocytes, 179, 182, 185, 201 Erythromycin, 62, 71, 85, 90, 163, 182, 201 Erythromycin Ethylsuccinate, 163, 201 Erythropoietin, 59, 72, 201 Esophageal, 3, 78, 82, 89, 136, 201, 202, 246 Esophageal Ulcer, 3, 78, 89, 202 Esophageal Varices, 202, 246 Esophagitis, 95, 136, 202 Esophagus, 136, 196, 201, 202, 209, 234, 250 Estrogen, 15, 32, 119, 202, 242, 246, 252 Estrogen receptor, 202 Ethanol, 54, 84, 202 Ethmoid, 124, 202, 232 Etidronate, 163, 202 Eukaryotic Cells, 202, 213, 230, 256 Excipients, 136, 202 Excitability, 202, 241 Excitation, 13, 202, 204 Exhaustion, 179, 202, 221 Exocrine, 202, 231 Exogenous, 17, 24, 186, 202, 206, 255 Exon, 29, 58, 177, 202 Expander, 202, 238 Extensor, 202, 240 External-beam radiation, 202, 216, 242 Extracellular, 42, 53, 54, 56, 178, 182, 184, 192, 202, 203, 204, 205, 215, 221, 248 Extracellular Matrix, 42, 56, 192, 203, 204, 205, 215, 221 Extracellular Matrix Proteins, 42, 203, 205, 221 Extracellular Space, 203 Extrapyramidal, 197, 203 Eye Infections, 176, 203 F Facial, 97, 203, 232 Facial Nerve, 203, 232 Fallopian Tubes, 162, 203 Family Planning, 157, 203 Fat, 14, 176, 179, 185, 187, 193, 194, 195, 199, 203, 219, 225, 231, 245, 246, 248, 251, 255 Fatigue, 7, 128, 203 Fatty acids, 203, 219 Feces, 203, 250 Femoral, 33, 83, 203, 210 Femoral Neck Fractures, 203, 210 Femoral Nerve, 83, 203 Femur, 203, 210
Index 267
Fetus, 201, 204, 235, 238, 249, 256 Fibrinogen, 204, 235, 253 Fibroblasts, 24, 56, 79, 87, 192, 204, 215 Fibronectin, 204, 206 Fibrosis, 56, 137, 204, 246 Filarioidea, 204, 217 Fissure, 196, 204, 238 Fistula, 91, 204 Fleroxacin, 68, 204 Flow Cytometry, 54, 204 Fluorescence, 15, 69, 83, 204 Fluorescence Polarization, 15, 204 Fluorescent Dyes, 204 Flushing, 197, 204 Foam Cells, 49, 204 Focal Adhesions, 50, 205, 250 Fold, 17, 204, 205, 223 Food Chain, 43, 205 Forearm, 100, 184, 205 Fractionation, 205, 252 Frontal Lobe, 205, 238 Fructosamine, 27, 205 Fructose, 205, 208 Fungi, 124, 137, 203, 205, 223, 249, 259 Fungus, 186, 205 G Galactosides, 183, 205 Gallbladder, 175, 183, 196, 205 Gamma Rays, 205, 242 Ganglia, 43, 175, 205, 227, 233 Ganglion, 29, 205, 244 Gap Junctions, 206, 251 Gas, 196, 206, 211, 228, 244, 257 Gas exchange, 206, 244, 257 Gastric, 106, 178, 197, 201, 206, 209, 233, 246 Gastric Acid, 178, 206 Gastrin, 206, 211 Gastrointestinal, 7, 124, 127, 135, 136, 181, 185, 190, 199, 201, 202, 206, 221, 229, 250, 257 Gastrointestinal tract, 124, 135, 136, 199, 202, 206 Gelatin, 143, 206, 208, 251, 253 Gelatinase A, 89, 206 Gels, 143, 206 Gene Targeting, 29, 51, 206 Genetic Engineering, 184, 191, 206 Genetic Markers, 163, 206 Genetic testing, 206, 237 Genetic transcription, 206, 239, 254 Genetics, 35, 47, 163, 206, 207
Genital, 68, 74, 80, 83, 99, 190, 206 Genotype, 207, 234 Gentamicins, 207, 247 Germinal Center, 8, 207 Gestation, 207, 233, 235 Giardiasis, 207, 223 Gland, 11, 34, 175, 176, 207, 220, 231, 232, 239, 242, 246, 250, 253 Glanders, 207, 222 Glial Fibrillary Acidic Protein, 88, 207 Glioma, 50, 207 Glomerular, 207, 243 Glomeruli, 207 Glomerulosclerosis, 12, 207 Glomerulus, 56, 207 Glucose, 27, 58, 181, 184, 188, 196, 205, 207, 208, 209, 214, 242 Glucose Intolerance, 196, 207 Glucuronic Acid, 207, 210 Glutamate, 13, 207 Glutathione Peroxidase, 49, 207 Glycine, 208, 247 Glycogen, 47, 189, 208 Glycoprotein, 62, 76, 106, 177, 201, 204, 208, 218, 225, 253, 255 Glycosaminoglycans, 203, 208, 240 Glycoside, 208, 212 Glycosidic, 208, 229 Glycosylation, 10, 44, 208 Goats, 208, 246 Gonorrhea, 187, 208 Governing Board, 208, 238 Grade, 60, 208 Graft, 11, 208, 211 Grafting, 24, 55, 208 Gram-negative, 187, 188, 189, 208, 209, 226, 229, 257 Gram-positive, 187, 188, 208, 229, 249, 250 Granulocytes, 208, 247, 258 Granuloma, 89, 208 Gravidity, 208, 232 Groin, 78, 208 Growth factors, 48, 56, 209 Guanylate Cyclase, 209, 228 Gyrase, 204, 209, 229 H Haemophilus, 114, 187, 209 Hair Cells, 31, 209 Half-Life, 187, 209 Halitosis, 124, 209 Haploid, 209, 235 Haptens, 176, 209
268 Doxycycline
Headache, 7, 209, 211, 214, 240 Headache Disorders, 209 Health Services, 19, 209 Health Status, 19, 209 Heart attack, 187, 209 Heartburn, 136, 209 Hematopoiesis, 25, 209 Hemoglobin, 27, 58, 179, 201, 209 Hemorrhage, 194, 198, 209, 210, 241, 250, 252 Hemorrhoids, 210, 246 Hemostasis, 23, 210, 215 Heparin, 8, 210, 236 Hepatic, 47, 57, 210 Hepatitis, 113, 210 Hepatocyte, 47, 210 Heredity, 175, 206, 210 Herpes, 158, 175, 210 Herpes virus, 158, 210 Herpes Zoster, 210 Heterodimer, 18, 210 Heterogeneity, 41, 176, 210 Heterogenic, 210 Heterogenous, 125, 210 Heterotrophic, 205, 210 Hip Fractures, 32, 203, 210 Hippocampus, 24, 196, 210, 218, 227, 250 Histology, 210, 227, 233 Homeostasis, 25, 135, 210 Homodimer, 211, 254 Homologous, 50, 194, 206, 211, 246, 251, 254 Hormone Replacement Therapy, 119, 211 Hormone therapy, 176, 211 Horny layer, 201, 211 Horseradish Peroxidase, 200, 211 Human growth hormone, 49, 211 Humoral, 59, 126, 211 Humour, 211 Hybrid, 18, 40, 56, 191, 211 Hybridization, 18, 20, 211 Hydrocephalus, 211, 216 Hydrogen, 175, 183, 186, 195, 203, 207, 211, 219, 224, 228, 229, 231, 234, 240, 251 Hydrogen Peroxide, 207, 211, 219, 251 Hydrolases, 9, 212, 234 Hydrolysis, 183, 212, 233, 234, 237, 240, 255 Hydroxylysine, 191, 212 Hydroxyproline, 191, 212 Hyperaemia, 192, 212 Hypercalcemia, 202, 212
Hyperpigmentation, 72, 212 Hyperplasia, 28, 212 Hypersensitivity, 177, 212, 245 Hypertension, 45, 187, 212, 216, 239 Hyperthyroidism, 212, 239 Hypertrophy, 193, 212, 255 Hypoglycemia, 79, 212 Hypotension, 197, 212 I Ibuprofen, 71, 212 Id, 46, 109, 116, 164, 170, 172, 212 Immune function, 212, 254 Immune Sera, 212 Immune system, 17, 126, 180, 184, 198, 212, 213, 220, 225, 226, 234, 256, 258 Immunity, 8, 99, 113, 124, 212, 213, 215, 254 Immunization, 126, 212 Immunoassay, 200, 213 Immunocompromised, 140, 213 Immunodeficiency, 54, 88, 126, 140, 213, 251 Immunodeficiency syndrome, 213, 251 Immunogenic, 54, 213 Immunoglobulin, 27, 180, 213, 224 Immunohistochemistry, 39, 213 Immunologic, 189, 212, 213, 233, 242 Immunology, 35, 53, 80, 98, 176, 204, 211, 213 Immunosuppressive, 63, 213 Immunotoxin, 23, 213 Impairment, 203, 213, 222, 239 Implant radiation, 213, 216, 217, 242 In situ, 18, 29, 39, 60, 142, 213 In Situ Hybridization, 39, 60, 213 Incision, 213, 216 Incubation, 44, 213 Indicative, 27, 213, 232, 257 Induction, 11, 16, 21, 28, 34, 35, 39, 44, 47, 85, 137, 140, 213 Infarction, 211, 213 Infertility, 31, 42, 214 Infiltration, 7, 37, 214, 239 Influenza, 124, 214 Infusion, 7, 46, 64, 214, 246 Ingestion, 3, 179, 209, 214, 237 Inhalation, 148, 176, 181, 214, 230, 237 Initiation, 38, 41, 214, 239, 250, 254 Initiator, 214, 215 Inlay, 214, 244 Inner ear, 31, 187, 214, 256 Innervation, 203, 214
Index 269
Inoculum, 8, 214 Inorganic, 214, 225 Inotropic, 197, 214 Insight, 42, 44, 214 Insulator, 214, 225 Insulin, 26, 33, 47, 82, 214, 255 Insulin-dependent diabetes mellitus, 214 Integrins, 50, 205, 214 Interferon, 113, 215 Interferon-alpha, 215 Interleukin-1, 76, 83, 215 Interleukin-12, 83, 215 Interleukin-2, 215 Interleukin-3, 35, 215 Interleukin-4, 60, 215 Interleukin-8, 17, 89, 215 Intermediate Filaments, 21, 215, 227, 250 Intermittent, 64, 87, 103, 215, 219 Internal radiation, 215, 217, 242 Interphase, 188, 216 Interstitial, 42, 43, 49, 56, 185, 203, 206, 216, 217, 243 Interstitial Collagenase, 42, 49, 206, 216 Intestinal, 57, 89, 124, 187, 194, 216 Intestinal Neoplasms, 57, 216 Intestine, 185, 216, 218, 250, 258 Intoxication, 70, 216, 258 Intracellular, 23, 30, 53, 135, 214, 215, 216, 228, 237, 247 Intracranial Hypertension, 76, 209, 211, 216 Intramuscular, 63, 72, 90, 216, 232 Intramuscular injection, 72, 216 Intravenous, 91, 100, 148, 214, 216, 232, 253 Intrinsic, 26, 176, 183, 216 Invasive, 11, 34, 50, 77, 212, 216, 220 Involuntary, 31, 42, 216, 226 Iodine, 216, 238 Iodoacetamide, 116, 216 Ion Channels, 182, 216, 228 Ions, 183, 197, 198, 211, 216 Iris, 193, 216, 241 Irradiation, 216, 243 Irrigation, 58, 99, 143, 217 Ischemia, 13, 21, 179, 182, 195, 217 Ischemic stroke, 13, 217 Isoenzyme, 194, 217 Ivermectin, 73, 217 J Joint, 6, 19, 77, 85, 101, 120, 163, 181, 190, 217, 230, 251
K Kb, 156, 217 Keratin, 69, 217, 246 Keratinocytes, 11, 79, 215, 217 Kerato, 10, 217 Kidney Disease, 12, 57, 122, 156, 217 Kinetics, 20, 76, 217 L Labile, 191, 217 Labyrinth, 191, 214, 217, 246, 257 Lactation, 218, 231 Laminin, 32, 183, 203, 218 Large Intestine, 196, 216, 218, 243, 248, 258 Larynx, 136, 218, 254 Latent, 42, 218, 238 Leptospirosis, 64, 93, 103, 108, 218 Lesion, 24, 48, 60, 208, 218, 219, 225, 246, 256 Lethal, 29, 56, 57, 183, 218 Leukemia, 16, 29, 76, 218 Leukocytes, 26, 183, 185, 189, 200, 208, 215, 218, 255 Levofloxacin, 71, 218 Library Services, 170, 218 Life cycle, 205, 218 Life Expectancy, 137, 218 Ligament, 218, 239 Ligands, 30, 53, 215, 218 Limbic, 178, 218, 238 Limbic System, 178, 218, 238 Lincomycin, 190, 218 Linkage, 206, 218 Lipid, 189, 204, 214, 219, 222, 225, 231, 255 Lipid Peroxidation, 219, 231 Lipopolysaccharide, 30, 208, 219 Liposomal, 84, 85, 219 Liposome, 80, 219 Lipoxygenase, 49, 181, 219 Lithium, 79, 219 Liver, 23, 30, 47, 175, 183, 196, 201, 202, 203, 205, 207, 208, 210, 219, 243 Loa, 219 Lobe, 211, 219, 232 Localization, 213, 219 Localized, 7, 29, 199, 214, 218, 219, 225, 235, 246, 256 Locomotion, 219, 235 Locomotor, 55, 219, 246 Loiasis, 74, 219 Long-Term Care, 12, 219 Loop, 135, 219 Lucida, 218, 219
270 Doxycycline
Luciferase, 32, 219 Lumbar, 33, 203, 220 Lupus, 163, 220 Lyme Disease, 13, 14, 117, 119, 120, 121, 148, 162, 220 Lymph, 33, 61, 67, 189, 200, 211, 220, 250 Lymph node, 33, 61, 189, 220 Lymphadenopathy, 67, 220 Lymphatic, 78, 200, 214, 220, 223, 236, 248, 249, 253 Lymphatic system, 220, 248, 249, 253 Lymphoblastic, 76, 220 Lymphocyte, 180, 220, 221, 222 Lymphoid, 16, 33, 180, 194, 207, 220 Lymphoma, 8, 113, 220 Lymphotoxin, 33, 220 Lysine, 40, 212, 220, 255 Lytic, 220, 258 M Macrophage, 22, 25, 35, 48, 49, 215, 220 Maculopapular, 220, 246 Magnetic Resonance Imaging, 199, 220 Maintenance therapy, 4, 65, 87, 221 Major Histocompatibility Complex, 215, 221 Malaise, 186, 221 Malaria, 9, 66, 70, 87, 92, 94, 95, 97, 101, 106, 107, 108, 162, 190, 221 Malaria, Falciparum, 221 Malaria, Vivax, 221 Malignant, 16, 37, 41, 65, 87, 92, 95, 100, 175, 180, 221, 223, 227, 230, 239, 242 Malignant mesothelioma, 221, 223 Malignant tumor, 175, 221, 230 Mammary, 11, 34, 221, 242, 252 Mandible, 178, 221, 244 Manic, 219, 221 Manifest, 124, 221 Matrix metalloproteinase, 7, 15, 19, 26, 33, 35, 37, 42, 76, 87, 92, 93, 97, 102, 221, 228 Maxillary, 124, 221, 232 Medial, 202, 221, 230 Mediate, 16, 27, 47, 197, 221 Mediator, 41, 56, 215, 221, 236 Medical Records, 222, 245 Medical Staff, 198, 222 MEDLINE, 157, 222 Mefloquine, 9, 78, 87, 92, 94, 95, 107, 108, 222 Megakaryocytes, 185, 222 Meiosis, 222, 223, 251 Melanin, 69, 216, 222, 234, 256
Melanocytes, 16, 212, 222 Melanosomes, 222 Melioidosis, 65, 87, 222 Membrane Fluidity, 38, 222 Memory, 8, 25, 27, 52, 195, 207, 222 Meninges, 187, 188, 194, 198, 222 Meningitis, 97, 222 Menopause, 222, 237, 239 Menstrual Cycle, 222, 239 Menstruation, 15, 222 Mental Disorders, 122, 222 Mental Health, iv, 5, 122, 156, 159, 223, 241 Mentors, 12, 223 Mercury, 204, 223 Mesenchymal, 49, 51, 201, 223 Mesenteric, 223, 237 Mesothelioma, 84, 221, 223 Meta-Analysis, 68, 223 Metastasis, 11, 74, 129, 221, 223 Metastatic, 11, 37, 129, 223, 246 Methionine, 22, 134, 223, 251 Metronidazole, 20, 82, 98, 124, 142, 143, 223 MI, 81, 173, 223 Microbe, 223, 252, 253 Microfilaments, 205, 215, 223, 250 Micronuclei, 41, 223 Microorganism, 191, 223, 232, 258 Microtubule-Associated Proteins, 224, 227 Microtubules, 215, 224, 227 Micturition, 43, 224 Migrans, 61, 71, 224 Migration, 32, 48, 50, 89, 90, 129, 224, 233 Milliliter, 185, 224 Minocycline, 61, 67, 69, 71, 80, 83, 88, 128, 133, 142, 143, 163, 224 Miscarriage, 162, 224 Mitochondria, 48, 224, 230 Mitochondrial Swelling, 224, 227 Mitosis, 181, 188, 223, 224 Mitotic, 41, 188, 224 Mitotic Spindle Apparatus, 188, 224 Mobility, 18, 224 Modification, 42, 54, 125, 206, 224, 241 Modulator, 44, 224 Monitor, 8, 194, 224, 229 Monoclonal, 93, 217, 224, 242 Monocyte, 48, 225 Mononuclear, 37, 42, 208, 225, 255 Monosomy, 179, 225 Morphogenesis, 49, 51, 225
Index 271
Morphological, 40, 55, 199, 205, 222, 225 Morphology, 32, 51, 62, 225 Motility, 225 Motion Sickness, 225, 226 Motor Neurons, 21, 225 Mouth Ulcer, 129, 225 Mucinous, 206, 225 Mucins, 225, 245 Mucociliary, 225, 247 Mucolytic, 185, 225 Mucopurulent, 96, 225 Mucosa, 129, 207, 220, 225, 226, 250 Mucus, 162, 225 Multicenter study, 89, 92, 225 Multiple sclerosis, 35, 225 Muscle Fibers, 14, 225, 226 Mutagenesis, 40, 82, 225 Mutagens, 225 Mutate, 51, 225 Myalgia, 214, 225 Mycoplasma, 71, 158, 188, 226 Myelin, 225, 226 Myocardial infarction, 85, 88, 90, 183, 194, 223, 226, 239, 258 Myocardium, 179, 223, 226 Myometrium, 24, 226 Myosin, 226, 250 Myotonia, 226, 241 N Naive, 30, 226 Naloxone, 226 Naltrexone, 158, 226 Narcotic, 175, 226 Nasal Cavity, 124, 226, 232 Nasal Mucosa, 214, 226 Nasal Septum, 226 Natural killer cells, 215, 226 Nausea, 7, 128, 197, 226, 240, 256 NCI, 1, 121, 155, 190, 226 Necrosis, 50, 181, 193, 213, 220, 223, 226, 247 Need, 3, 4, 5, 19, 26, 36, 52, 142, 158, 165, 176, 190, 208, 221, 227, 253 Neocortex, 24, 227 Neonatal, 49, 51, 58, 162, 227 Neoplasia, 39, 41, 227 Neoplasm, 227, 255 Neoplastic, 39, 41, 57, 178, 220, 227 Nephron, 207, 227 Nephropathy, 26, 217, 227 Nerve Endings, 227, 252
Nervous System, 8, 44, 176, 188, 190, 209, 220, 222, 227, 228, 233, 246, 251 Netilmicin, 102, 227 Networks, 29, 227, 252 Neural, 54, 66, 176, 178, 211, 227 Neurodegenerative Diseases, 53, 54, 60, 227 Neurofibrillary Tangles, 52, 227 Neurofilaments, 227 Neurologic, 7, 13, 53, 211, 227 Neuromuscular, 175, 227, 228 Neuromuscular Junction, 175, 228 Neuronal, 13, 21, 31, 38, 43, 53, 190, 227, 228 Neurons, 13, 21, 38, 43, 44, 53, 54, 59, 195, 196, 205, 225, 227, 228, 251 Neuropathy, 26, 158, 228 Neuropeptide, 43, 228 Neurophysiology, 196, 228 Neuroretinitis, 228, 244 Neurotoxic, 53, 228 Neurotransmitters, 228 Neutrons, 177, 216, 228, 242 Neutrophil, 19, 66, 85, 89, 112, 177, 228 Neutrophil Collagenase, 85, 228 Nickel, 131, 228 Night Blindness, 228, 244 Nitric Oxide, 7, 26, 100, 228 Nitrogen, 177, 203, 228, 255 Nocturia, 43, 228 Norepinephrine, 176, 197, 228 Norfloxacin, 82, 229 Nosocomial, 40, 229 Nuclear, 10, 27, 40, 47, 49, 55, 183, 199, 202, 205, 218, 227, 229, 239, 244, 252 Nucleates, 188, 229 Nuclei, 177, 178, 199, 206, 218, 220, 223, 224, 228, 229, 230, 236, 240, 252 Nucleic acid, 211, 213, 225, 228, 229, 238, 241 Nucleic Acid Hybridization, 211, 229 Nucleotidases, 212, 229 Nucleus Accumbens, 55, 229 O Ocular, 89, 229, 230 Ofloxacin, 63, 64, 102, 163, 229 Ointments, 143, 197, 229 Oligo, 16, 229 Oligosaccharides, 38, 229 Onchocerciasis, 76, 229 Oncogene, 12, 28, 34, 113, 230 Oncogenic, 6, 34, 41, 215, 230
272 Doxycycline
Opacity, 196, 230 Operon, 139, 230, 239, 243 Opsin, 230, 244 Optic Chiasm, 230 Optic Nerve, 29, 228, 230, 231, 240, 244 Oral Health, 230 Oral Hygiene, 4, 103, 209, 230 Orderly, 11, 230 Organelles, 188, 195, 222, 230 Ornithosis, 230, 240 Osmotic, 224, 230, 247 Osteoarthritis, 18, 20, 101, 120, 148, 163, 230 Osteogenic sarcoma, 230, 231 Osteoporosis, 29, 30, 32, 133, 163, 230, 242 Osteosarcoma, 85, 230, 231 Ototoxic, 32, 231 Outpatient, 31, 42, 231 Ovaries, 203, 231, 247 Ovary, 194, 231, 237, 250 Overexpress, 18, 54, 231 Overweight, 109, 120, 231 Ovum, 194, 207, 218, 231, 239 Oxacillin, 191, 231 Oxidation, 42, 44, 48, 175, 180, 181, 195, 197, 207, 219, 231 Oxidative Stress, 44, 231 Oxytetracycline, 130, 132, 231 Oxytocin, 24, 231, 253 P Pachymeningitis, 222, 231 Palladium, 130, 231 Palliative, 231, 252 Palsy, 97, 231 Pancreas, 30, 175, 196, 214, 231, 249, 255 Panniculitis, 98, 231 Papilla, 232 Papillary, 41, 232 Paralysis, 91, 175, 232 Paranasal Sinuses, 232, 247 Parasite, 30, 205, 217, 232, 255 Parasitic, 194, 219, 232, 255 Parenteral, 42, 127, 128, 232 Parietal, 232, 236 Parity, 34, 232 Parotid, 77, 232 Particle, 126, 219, 232, 254 Parturition, 24, 232 Patch, 232, 254 Pathogen, 26, 126, 213, 214, 232 Pathogenesis, 6, 21, 33, 36, 38, 48, 51, 53, 232
Pathologic, 10, 20, 35, 39, 42, 181, 184, 186, 193, 212, 232, 240, 243, 257 Pathologic Processes, 181, 232 Pathophysiology, 5, 27, 42, 44, 45, 107, 232 Patient Education, 162, 168, 170, 173, 232 Pelvic, 31, 42, 43, 90, 162, 232, 239 Pelvic inflammatory disease, 42, 90, 162, 232 Penicillin, 51, 61, 62, 72, 132, 141, 148, 164, 178, 179, 232 Penis, 162, 192, 232 Pentoxifylline, 158, 232 Peptic, 233, 246 Peptic Ulcer, 233, 246 Peptic Ulcer Hemorrhage, 233, 246 Peptide, 16, 22, 158, 191, 200, 212, 217, 233, 237, 239, 240 Peptide Hydrolases, 200, 212, 233 Percutaneous, 95, 233 Perennial, 233, 255 Perforation, 233, 258 Pericardial Effusion, 92, 233 Pericardium, 233 Perinatal, 24, 29, 233 Periodontal disease, 4, 5, 115, 124, 133, 142, 178, 233 Periodontal Pocket, 108, 233 Periodontics, 5, 233 Peripheral blood, 30, 60, 215, 233 Peripheral Nervous System, 227, 231, 233, 250 Peritoneal, 181, 233 Peritoneal Cavity, 181, 233 Peritonitis, 233, 258 PH, 37, 185, 234 Phagocyte, 38, 234 Pharmaceutical Preparations, 129, 188, 202, 206, 234 Pharmaceutical Solutions, 197, 234 Pharmacodynamic, 63, 64, 90, 103, 107, 234 Pharmacokinetic, 91, 101, 234 Pharmacologic, 36, 179, 209, 234, 254 Pharynx, 136, 214, 226, 234 Phenotype, 10, 25, 27, 39, 41, 55, 56, 57, 98, 234 Phenylalanine, 234, 256 Phorbol, 38, 42, 234 Phosphodiesterase, 24, 232, 234 Phospholipases, 234, 247 Phospholipids, 203, 222, 234
Index 273
Phosphoric Monoester Hydrolases, 212, 234 Phosphorus, 186, 234 Phosphorylated, 191, 234 Phosphorylates, 6, 234 Phosphorylation, 6, 10, 47, 51, 234 Photocoagulation, 191, 234 Photoreceptor, 45, 55, 235 Photosensitivity, 67, 91, 235 Physiologic, 27, 177, 184, 209, 222, 235, 242, 243 Physiology, 44, 45, 88, 106, 175, 228, 233, 235, 257 Pigment, 222, 235 Pigmentation, 212, 235 Pilot study, 16, 58, 76, 94, 103, 115, 235 Placenta, 235, 239 Plague, 162, 235 Plants, 132, 137, 177, 189, 190, 205, 207, 208, 225, 229, 235, 237, 249, 254, 255 Plaque, 48, 83, 100, 113, 142, 189, 235 Plasma cells, 180, 235 Plasma protein, 235, 247 Plasmid, 65, 131, 235, 257 Plasmin, 235, 236 Plasminogen, 38, 235, 236 Plasminogen Activators, 235, 236 Plasticity, 31, 43, 54, 236 Platelet Activation, 236, 247 Platelet Aggregation, 178, 228, 233, 236 Platelet Factor 4, 215, 236 Platelets, 181, 183, 222, 228, 236, 253 Platinum, 219, 231, 236 Platyhelminths, 217, 236 Pleated, 217, 236 Pleomorphic, 229, 236 Pleura, 236 Pleural, 65, 87, 95, 100, 236 Pleural cavity, 236 Pleural Effusion, 65, 87, 95, 100, 236 Pleurodesis, 65, 66, 69, 236 Plexus, 203, 236 Point Mutation, 55, 237 Poisoning, 116, 216, 223, 226, 237 Pollen, 124, 237 Polycystic, 57, 237 Polymerase, 29, 54, 237, 239, 243 Polymerase Chain Reaction, 29, 54, 237 Polymers, 184, 237, 240 Polypeptide, 43, 178, 191, 201, 204, 211, 235, 237, 259 Polyposis, 56, 237
Polysaccharide, 180, 188, 237, 240 Population Dynamics, 86, 237 Portal Vein, 23, 237 Posterior, 178, 190, 197, 216, 231, 237 Postmenopausal, 30, 32, 119, 230, 237, 242 Postnatal, 14, 237, 249 Postoperative, 95, 237 Postsynaptic, 237, 247, 251 Post-synaptic, 237, 252 Potassium, 128, 132, 237, 241 Potentiate, 63, 238 Potentiation, 91, 107, 238, 247 Povidone, 58, 238 Povidone-Iodine, 58, 238 Practice Guidelines, 159, 238 Precancerous, 189, 238 Preclinical, 54, 55, 238 Precursor, 25, 52, 114, 189, 197, 198, 200, 228, 234, 235, 238, 254, 255, 256 Predisposition, 21, 163, 238 Prefrontal Cortex, 55, 238 Prenatal, 199, 238 Presynaptic, 227, 238, 251 Prevalence, 4, 41, 238 Prickle, 217, 238 Primary endpoint, 7, 58, 238 Primary tumor, 6, 238 Prion, 38, 43, 62, 188, 238 Probenecid, 42, 238 Procaine, 148, 164, 239 Progesterone, 15, 239 Progestogen, 15, 239 Progression, 11, 16, 18, 20, 21, 27, 35, 36, 41, 48, 50, 56, 120, 179, 239 Progressive, 37, 52, 59, 188, 190, 193, 195, 198, 208, 226, 227, 230, 236, 239, 243, 244, 255 Projection, 195, 229, 230, 238, 239 Proliferating Cell Nuclear Antigen, 39, 239 Proline, 191, 212, 239 Promotor, 36, 239, 244 Prophylaxis, 65, 68, 70, 74, 87, 92, 93, 97, 106, 107, 108, 139, 164, 239, 256, 258 Proportional, 38, 200, 239 Propranolol, 129, 239 Prospective study, 100, 239 Prostate, 39, 80, 128, 239 Protease, 18, 52, 177, 239 Protein C, 36, 47, 103, 108, 178, 183, 217, 239 Protein Isoforms, 11, 177, 240
274 Doxycycline
Protein S, 44, 133, 134, 141, 184, 201, 207, 211, 240, 245, 250, 252 Protein Subunits, 44, 240 Proteinuria, 27, 207, 240 Proteoglycan, 7, 236, 240 Proteolytic, 85, 93, 177, 192, 204, 235, 236, 240 Protons, 177, 211, 240, 242 Protozoa, 217, 223, 240, 249 Provirus, 126, 240 Proximal, 56, 197, 226, 238, 240 Pruritus, 230, 240, 246 Pseudotumor Cerebri, 216, 240 Psittaci, 63, 230, 240 Psittacosis, 111, 240 Psoriasis, 10, 240 Puberty, 34, 240 Public Health, 9, 32, 33, 66, 73, 140, 159, 164, 241 Public Policy, 157, 241 Publishing, 4, 61, 142, 241 Pulmonary, 49, 51, 93, 113, 177, 184, 185, 193, 200, 241, 251, 257, 258 Pulmonary Artery, 184, 241, 257 Pulmonary Embolism, 241, 258 Pulmonary hypertension, 193, 241 Pulse, 68, 224, 241 Pupil, 193, 241 Purines, 241, 247 Purpura, 104, 241 Purulent, 241, 256 Pustular, 175, 241 Q Quality of Life, 26, 31, 136, 241 Quiescent, 11, 241 Quinidine, 136, 190, 241 Quinine, 9, 94, 107, 108, 190, 241 R Race, 224, 241 Radiation, 139, 176, 179, 200, 202, 204, 205, 216, 223, 242, 258 Radiation therapy, 139, 176, 202, 205, 216, 217, 242 Radioactive, 209, 211, 213, 215, 217, 229, 230, 242 Radiolabeled, 217, 238, 242 Radiological, 233, 242 Radiotherapy, 185, 217, 242 Raloxifene, 242, 246 Randomized, 6, 19, 31, 58, 65, 66, 68, 87, 89, 93, 94, 95, 97, 100, 103, 108, 119, 120, 198, 242
Randomized clinical trial, 31, 65, 68, 242 Reabsorption, 238, 242 Reactive Oxygen Species, 113, 242 Reagent, 197, 216, 220, 242 Recombinant, 12, 14, 22, 23, 26, 43, 54, 55, 63, 66, 85, 93, 112, 135, 158, 242, 243, 257 Recombinant Proteins, 135, 243 Recombination, 27, 50, 58, 206, 243 Reconstitution, 34, 47, 94, 243 Rectum, 180, 185, 196, 206, 218, 239, 243, 251 Recurrence, 73, 243 Reductase, 48, 243 Refer, 1, 126, 186, 191, 197, 205, 210, 219, 226, 228, 229, 243, 257 Refraction, 179, 243, 248 Regeneration, 29, 31, 93, 243 Regimen, 8, 19, 35, 58, 81, 99, 163, 198, 243 Regurgitation, 209, 243 Remission, 221, 243 Renal failure, 59, 243 Renal tubular, 239, 243 Renin, 186, 243 Renin-Angiotensin System, 186, 243 Replicon, 139, 243 Repopulation, 20, 243 Repressor, 50, 137, 139, 230, 243 Resorption, 33, 177, 211, 242, 243 Respiration, 224, 244 Respiratory distress syndrome, 186, 244 Respiratory failure, 49, 66, 244 Response Elements, 6, 27, 244 Restoration, 32, 243, 244, 258 Retina, 45, 189, 190, 228, 230, 244, 245, 258 Retinal, 29, 45, 55, 192, 230, 244 Retinal Ganglion Cells, 230, 244 Retinitis, 45, 55, 244 Retinitis Pigmentosa, 55, 244 Retinol, 244 Retinopathy, 26, 235, 244 Retrograde, 80, 102, 244 Retrospective, 112, 244, 245 Retrospective study, 112, 245 Retroviral vector, 46, 245 Retrovirus, 43, 245 Reversion, 140, 245 Rheology, 232, 245 Rheumatism, 66, 73, 97, 98, 100, 112, 212, 245 Rheumatoid, 6, 68, 76, 85, 87, 91, 100, 124, 133, 148, 163, 245
Index 275
Rheumatoid arthritis, 6, 68, 76, 85, 91, 100, 124, 133, 148, 163, 245 Ribosome, 245, 254 Rigidity, 235, 245 Risk factor, 45, 100, 239, 245 Ristocetin, 245, 256 Rod, 45, 182, 183, 209, 235, 245 Root Planing, 4, 20, 81, 97, 99, 100, 103, 142, 245 S S Phase, 4, 245 Saline, 185, 245 Saliva, 91, 100, 101, 245 Salivary, 196, 203, 245, 250 Salivary glands, 196, 203, 245 Schizoid, 245, 258 Schizophrenia, 245, 246, 258 Schizotypal Personality Disorder, 245, 258 Scleroproteins, 217, 246 Sclerosis, 13, 21, 77, 225, 246 Sclerotherapy, 77, 83, 91, 95, 149, 246 Scrapie, 38, 44, 246 Screening, 52, 58, 191, 246 Scrub Typhus, 63, 246 Sebum, 175, 246 Secondary tumor, 223, 246 Secretion, 22, 48, 73, 135, 175, 201, 211, 214, 218, 225, 246, 254 Secretory, 246, 251 Segmental, 207, 246 Segregation, 243, 246 Selective estrogen receptor modulator, 163, 242, 246, 252 Semen, 239, 246 Semicircular canal, 214, 246 Semisynthetic, 178, 187, 188, 190, 217, 224, 227, 246 Senile, 231, 246 Sensor, 69, 246 Sequencing, 237, 247 Sequester, 18, 247, 251 Serine, 129, 200, 247, 255 Serum, 27, 33, 36, 50, 58, 75, 84, 101, 114, 178, 191, 194, 212, 233, 243, 247, 255 Serum Albumin, 114, 247 Sex Characteristics, 240, 247, 252 Sexually Transmitted Diseases, 68, 72, 73, 87, 247 Shock, 247, 255 Side effect, 18, 23, 55, 120, 124, 128, 151, 176, 184, 222, 247, 253 Signal Transduction, 47, 247
Single-agent, 9, 247 Sinusitis, 100, 124, 247 Sisomicin, 131, 247 Skeletal, 14, 30, 59, 194, 241, 247 Skeleton, 175, 203, 217, 247 Skull, 194, 247, 252 Small intestine, 183, 198, 207, 211, 216, 248, 255 Smallpox, 248, 256 Smear Layer, 112, 248 Smooth muscle, 24, 35, 42, 178, 192, 204, 226, 243, 248, 250 Social Environment, 241, 248 Sodium, 128, 132, 241, 242, 248 Soft tissue, 185, 247, 248 Solid tumor, 179, 184, 248 Solvent, 127, 134, 202, 230, 234, 248 Soma, 248 Somatic, 43, 199, 211, 218, 222, 224, 233, 238, 248 Spatial disorientation, 197, 248 Specialist, 165, 248 Specificity, 10, 15, 18, 36, 97, 137, 176, 181, 200, 248 Spectrophotometry, 114, 248 Spectrum, 83, 124, 125, 131, 132, 134, 204, 229, 248 Sperm, 190, 237, 249 Sphincter, 218, 249 Spinal cord, 182, 185, 188, 189, 198, 203, 205, 222, 227, 228, 231, 233, 249 Spinous, 201, 217, 249 Spiramycin, 142, 249 Spirochete, 8, 120, 220, 249 Spleen, 30, 220, 249 Splenic Vein, 237, 249 Spondylitis, 163, 249 Sporadic, 22, 227, 249 Spores, 214, 249 Spotting, 19, 249 Staphylococcal Infections, 132, 249 Staphylococcus, 224, 249 Statistically significant, 4, 249 Stem cell transplantation, 54, 249 Stem Cells, 13, 31, 36, 54, 201, 249 Sterile, 125, 181, 249 Sterility, 84, 162, 214, 249 Sternum, 136, 249 Steroids, 194, 195, 249 Stillbirth, 162, 249 Stimulus, 193, 198, 202, 214, 215, 216, 250, 253
276 Doxycycline
Stomach, 124, 136, 175, 196, 202, 206, 211, 226, 233, 234, 248, 249, 250, 258 Stool, 86, 218, 250 Strand, 237, 250 Streptococci, 132, 250 Streptomycin, 62, 250 Stress, 44, 50, 187, 204, 226, 231, 238, 245, 250 Stress Fibers, 50, 250 Striatum, 55, 60, 229, 250 Stroke, 13, 93, 111, 122, 156, 187, 217, 250 Stroma, 11, 216, 250 Stromal, 185, 250 Stromal Cells, 185, 250 Subacute, 214, 247, 250 Subarachnoid, 73, 209, 250 Subclinical, 64, 214, 250 Subcutaneous, 198, 219, 230, 231, 232, 250 Subiculum, 210, 250 Submaxillary, 201, 250 Subspecies, 248, 250 Substance P, 201, 239, 243, 245, 246, 250 Substrate, 189, 200, 205, 212, 250 Subtrochanteric, 210, 251 Sulfadiazine, 132, 251 Sulfur, 203, 223, 251 Superoxide, 22, 251 Superoxide Dismutase, 22, 251 Supplementation, 23, 251 Suppositories, 206, 251 Suppression, 5, 20, 57, 251 Suppressive, 57, 251 Surfactant, 40, 49, 251 Sympathomimetic, 197, 201, 229, 251 Symphysis, 239, 251 Symptomatic, 18, 35, 251 Symptomatology, 27, 251 Synapses, 38, 228, 251 Synaptic, 247, 251 Synaptic Vesicles, 251 Synaptosomes, 38, 252 Synergistic, 47, 102, 131, 252 Synovial, 87, 252 Systolic, 212, 252 T Tachycardia, 182, 252 Tachypnea, 182, 252 Tamoxifen, 82, 246, 252 Tamponade, 92, 252 Telophase, 223, 252 Temporal, 25, 26, 28, 32, 33, 37, 56, 58, 178, 209, 210, 252
Temporal Lobe, 178, 252 Testosterone, 243, 252 Tetracycline Resistance, 137, 252 Thalamus, 196, 218, 238, 252 Theophylline, 136, 241, 252 Therapeutics, 152, 252 Thermal, 179, 181, 197, 228, 237, 252 Thigh, 203, 208, 252 Thorax, 175, 220, 253 Threonine, 247, 253 Threshold, 202, 212, 253 Thrombin, 204, 236, 239, 253 Thrombolytic, 236, 253 Thrombomodulin, 239, 253 Thrombophlebitis, 7, 253 Thrombosis, 183, 215, 240, 246, 250, 253 Thrombus, 194, 213, 217, 236, 253, 257 Thymus, 158, 213, 220, 253 Thyroid, 41, 49, 212, 216, 253, 256 Thyroid Gland, 212, 253 Thyroid Neoplasms, 41, 253 Ticks, 8, 13, 82, 120, 121, 220, 253 Tocolytic Agents, 24, 253 Tolerance, 9, 87, 128, 175, 207, 253 Tomography, 185, 253 Tooth Loss, 32, 253 Topical, 89, 136, 142, 189, 202, 211, 238, 253 Toxic, iv, 16, 25, 60, 128, 190, 200, 212, 213, 228, 253, 254, 256 Toxicity, 21, 35, 79, 107, 127, 134, 198, 223, 227, 245, 253 Toxicology, 60, 158, 253 Toxins, 10, 180, 207, 214, 254 Toxoplasmosis, 182, 251, 254 Trace element, 228, 254 Trachea, 185, 186, 218, 234, 253, 254 Trans-Activators, 97, 254 Transcriptase, 54, 245, 254 Transcription Factors, 6, 10, 13, 29, 46, 47, 49, 56, 244, 254 Transdermal, 84, 254 Transduction, 12, 59, 247, 254 Transfection, 13, 39, 126, 184, 254 Transfer Factor, 213, 254 Transferases, 208, 254 Transforming Growth Factor beta, 73, 106, 254 Transgenes, 8, 11, 13, 22, 24, 25, 57, 254 Translation, 39, 51, 201, 207, 254 Translational, 12, 254 Translocation, 9, 27, 201, 254
Index 277
Transmitter, 24, 175, 182, 197, 216, 222, 229, 251, 255 Transplantation, 29, 47, 54, 190, 213, 221, 255 Trauma, 13, 32, 163, 202, 227, 255 Trees, 132, 190, 255 Trichomoniasis, 223, 255 Tricuspid Atresia, 193, 255 Triglyceride, 58, 255 Trimethoprim-sulfamethoxazole, 65, 255 Trisomy, 179, 255 Tropical Medicine, 30, 68, 70, 87, 95, 101, 106, 107, 255 Tropoelastin, 42, 255 Trypsin, 177, 255 Tryptophan, 191, 255 Tubercle, 229, 255 Tuberculosis, 193, 220, 255 Tuberous Sclerosis, 6, 57, 255 Tumor Necrosis Factor, 33, 87, 220, 255 Tumor suppressor gene, 56, 255 Tumour, 205, 255 Type 2 diabetes, 58, 255 Tyrosine, 37, 63, 66, 86, 107, 197, 256 U Ubiquitin, 227, 256 Ulcer, 3, 195, 202, 233, 256 Ulceration, 3, 82, 129, 136, 195, 207, 256 Unconscious, 195, 212, 256 Uremia, 243, 256 Ureters, 256 Urethra, 163, 232, 239, 256 Urethritis, 65, 67, 70, 73, 256 Uricosuric, 238, 256 Urinary, 7, 43, 81, 107, 114, 115, 127, 187, 190, 195, 199, 211, 229, 256 Urinary tract, 43, 187, 256 Urine, 27, 33, 163, 184, 194, 197, 201, 224, 229, 240, 256 Urokinase, 38, 256 Urothelium, 28, 256 Uterine Contraction, 231, 253, 256 Uterus, 189, 194, 198, 200, 203, 222, 226, 231, 239, 252, 256 V Vaccination, 126, 256 Vaccine, 17, 63, 84, 126, 139, 140, 158, 163, 176, 256 Vaccinia, 140, 256 Vagina, 186, 189, 196, 222, 249, 252, 256 Vaginal, 158, 162, 256 Vaginitis, 7, 186, 256
Vancomycin, 64, 86, 102, 103, 256 Varicose, 246, 256 Varicose vein, 246, 256 Variola, 256, 257 Vascular, 15, 42, 75, 78, 92, 94, 95, 103, 190, 200, 209, 213, 214, 228, 235, 236, 253, 257 Vasodilation, 197, 257 Vasodilator, 185, 197, 257 Vector, 17, 23, 29, 49, 54, 55, 59, 66, 72, 79, 83, 135, 219, 254, 257 Vein, 179, 216, 229, 232, 237, 249, 253, 257 Venous, 183, 210, 240, 255, 257, 258 Venous Thrombosis, 183, 257, 258 Ventilation, 186, 257 Ventral, 229, 257 Ventricle, 178, 182, 187, 193, 210, 229, 241, 252, 255, 257 Ventricular, 193, 211, 255, 257 Venules, 184, 186, 257 Vertebrae, 32, 249, 257 Vestibular, 209, 257 Vestibule, 191, 214, 246, 257 Veterinary Medicine, 106, 157, 257 Vibrio, 82, 93, 189, 257 Vibrio cholerae, 82, 93, 189, 257 Vinca Alkaloids, 257 Vincristine, 112, 257 Viral, 12, 17, 18, 25, 45, 53, 60, 126, 139, 193, 214, 230, 245, 254, 257 Viral vector, 17, 53, 257 Virulence, 40, 126, 182, 253, 258 Virulent, 126, 140, 258 Virus, 17, 26, 45, 54, 55, 59, 60, 63, 88, 113, 126, 135, 139, 140, 183, 188, 200, 206, 215, 235, 240, 245, 248, 254, 257, 258 Viscera, 248, 258 Viscosity, 127, 245, 258 Visual field, 230, 240, 244, 258 Vitreous Body, 189, 244, 258 Vitro, 11, 13, 14, 20, 22, 26, 28, 32, 37, 46, 50, 56, 59, 61, 63, 64, 68, 71, 79, 80, 84, 85, 89, 91, 94, 103, 106, 107, 114, 115, 210, 213, 237, 245, 258 Vivo, 5, 9, 10, 11, 13, 17, 18, 20, 21, 22, 26, 27, 29, 31, 32, 38, 41, 43, 44, 46, 47, 48, 50, 51, 54, 55, 57, 59, 60, 61, 64, 79, 80, 97, 199, 210, 213, 258 Volition, 216, 258 Volvulus, 73, 258 W Warfarin, 69, 258
278 Doxycycline
White blood cell, 180, 218, 220, 225, 226, 228, 235, 258 Windpipe, 186, 234, 253, 258 Withdrawal, 20, 26, 258 Wound Healing, 26, 99, 215, 221, 258 X Xenograft, 50, 179, 258
X-ray, 18, 33, 185, 187, 204, 205, 216, 229, 242, 258 Y Yeasts, 186, 205, 234, 259 Z Zymogen, 239, 259
Index 279
280 Doxycycline
