DEXAMETHASONE A M EDICAL D ICTIONARY , B IBLIOGRAPHY , AND A NNOTATED R ESEARCH G UIDE TO I NTERNET R EFERENCES
J AMES N. P ARKER , M.D. AND P HILIP M. P ARKER , P H .D., E DITORS
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ICON Health Publications ICON Group International, Inc. 4370 La Jolla Village Drive, 4th Floor San Diego, CA 92122 USA Copyright ©2004 by ICON Group International, Inc. Copyright ©2004 by ICON Group International, Inc. All rights reserved. This book is protected by copyright. No part of it may be reproduced, stored in a retrieval system, or transmitted in any form or by any means, electronic, mechanical, photocopying, recording, or otherwise, without written permission from the publisher. Printed in the United States of America. Last digit indicates print number: 10 9 8 7 6 4 5 3 2 1 Publisher, Health Care: Philip Parker, Ph.D. Editor(s): James Parker, M.D., Philip Parker, Ph.D. Publisher's note: The ideas, procedures, and suggestions contained in this book are not intended for the diagnosis or treatment of a health problem. As new medical or scientific information becomes available from academic and clinical research, recommended treatments and drug therapies may undergo changes. The authors, editors, and publisher have attempted to make the information in this book up to date and accurate in accord with accepted standards at the time of publication. The authors, editors, and publisher are not responsible for errors or omissions or for consequences from application of the book, and make no warranty, expressed or implied, in regard to the contents of this book. Any practice described in this book should be applied by the reader in accordance with professional standards of care used in regard to the unique circumstances that may apply in each situation. The reader is advised to always check product information (package inserts) for changes and new information regarding dosage and contraindications before prescribing any drug or pharmacological product. Caution is especially urged when using new or infrequently ordered drugs, herbal remedies, vitamins and supplements, alternative therapies, complementary therapies and medicines, and integrative medical treatments. Cataloging-in-Publication Data Parker, James N., 1961Parker, Philip M., 1960Dexamethasone: 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: 0-597-84389-9 1. Dexamethasone-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 dexamethasone. 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 DEXAMETHASONE .................................................................................... 3 Overview........................................................................................................................................ 3 The Combined Health Information Database................................................................................. 3 Federally Funded Research on Dexamethasone ............................................................................. 4 E-Journals: PubMed Central ....................................................................................................... 59 The National Library of Medicine: PubMed ................................................................................ 65 CHAPTER 2. NUTRITION AND DEXAMETHASONE ........................................................................ 115 Overview.................................................................................................................................... 115 Finding Nutrition Studies on Dexamethasone .......................................................................... 115 Federal Resources on Nutrition ................................................................................................. 117 Additional Web Resources ......................................................................................................... 117 CHAPTER 3. ALTERNATIVE MEDICINE AND DEXAMETHASONE .................................................. 119 Overview.................................................................................................................................... 119 National Center for Complementary and Alternative Medicine................................................ 119 Additional Web Resources ......................................................................................................... 130 General References ..................................................................................................................... 132 CHAPTER 4. DISSERTATIONS ON DEXAMETHASONE .................................................................... 133 Overview.................................................................................................................................... 133 Dissertations on Dexamethasone ............................................................................................... 133 Keeping Current ........................................................................................................................ 134 CHAPTER 5. CLINICAL TRIALS AND DEXAMETHASONE ............................................................... 135 Overview.................................................................................................................................... 135 Recent Trials on Dexamethasone ............................................................................................... 135 Keeping Current on Clinical Trials ........................................................................................... 141 CHAPTER 6. PATENTS ON DEXAMETHASONE ............................................................................... 143 Overview.................................................................................................................................... 143 Patents on Dexamethasone ........................................................................................................ 143 Patent Applications on Dexamethasone..................................................................................... 167 Keeping Current ........................................................................................................................ 177 CHAPTER 7. BOOKS ON DEXAMETHASONE .................................................................................. 179 Overview.................................................................................................................................... 179 Book Summaries: Online Booksellers......................................................................................... 179 The National Library of Medicine Book Index ........................................................................... 179 Chapters on Dexamethasone ...................................................................................................... 180 CHAPTER 8. PERIODICALS AND NEWS ON DEXAMETHASONE ..................................................... 183 Overview.................................................................................................................................... 183 News Services and Press Releases.............................................................................................. 183 Newsletter Articles .................................................................................................................... 186 Academic Periodicals covering Dexamethasone......................................................................... 187 CHAPTER 9. RESEARCHING MEDICATIONS .................................................................................. 189 Overview.................................................................................................................................... 189 U.S. Pharmacopeia..................................................................................................................... 189 Commercial Databases ............................................................................................................... 190 APPENDIX A. PHYSICIAN RESOURCES .......................................................................................... 195 Overview.................................................................................................................................... 195 NIH Guidelines.......................................................................................................................... 195 NIH Databases........................................................................................................................... 197 Other Commercial Databases..................................................................................................... 199 The Genome Project and Dexamethasone .................................................................................. 199 APPENDIX B. PATIENT RESOURCES ............................................................................................... 203
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Overview.................................................................................................................................... 203 Patient Guideline Sources.......................................................................................................... 203 Finding Associations.................................................................................................................. 205 APPENDIX C. FINDING MEDICAL LIBRARIES ................................................................................ 207 Overview.................................................................................................................................... 207 Preparation................................................................................................................................. 207 Finding a Local Medical Library................................................................................................ 207 Medical Libraries in the U.S. and Canada ................................................................................. 207 ONLINE GLOSSARIES................................................................................................................ 213 Online Dictionary Directories ................................................................................................... 214 DEXAMETHASONE DICTIONARY ......................................................................................... 215 INDEX .............................................................................................................................................. 323
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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 dexamethasone 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 dexamethasone, 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 dexamethasone, 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 dexamethasone. 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 dexamethasone, 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 dexamethasone. The Editors
1
From the NIH, National Cancer Institute (NCI): http://www.cancer.gov/cancerinfo/ten-things-to-know.
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CHAPTER 1. STUDIES ON DEXAMETHASONE Overview In this chapter, we will show you how to locate peer-reviewed references and studies on dexamethasone.
The Combined Health Information Database The Combined Health Information Database summarizes studies across numerous federal agencies. To limit your investigation to research studies and dexamethasone, 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 “dexamethasone” (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: •
Dexamethasone Perfusion of the Labyrinth Plus Intravenous Dexamethasone for Meniere's Disease Source: Otolaryngologic Clinics of North America. 29(2): 353-358. April 1996. Summary: This article describes the use of dexamethasone perfusion of the labyrinth, plus intravenous dexamethasone, for treating Meniere's disease. Topics include the diagnosis of Meniere's disease, the techniques of dexamethasone perfusion, the results of operations, and patient selection. The authors present one brief case report. It is believed by many that Meniere's disease is usually triggered and perpetuated by an immune response in an ear with a small, misplaced, and malfunctioning endolymphatic sac. If this is correct, the authors contend that the logical first treatment is potent antiinflammatory steroids, especially dexamethasone, by perfusion through the round window plus intravenously. 1 figure. 2 tables. 24 references.
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Federally Funded Research on Dexamethasone The U.S. Government supports a variety of research studies relating to dexamethasone. 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 dexamethasone. 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 dexamethasone. The following is typical of the type of information found when searching the CRISP database for dexamethasone: •
Project Title: A PROTEOMICS
GENETIC
SCREEN
FOR
PROTEIN
EVOLUTION
AND
Principal Investigator & Institution: Cornish, Virginia W.; Chemistry; Columbia Univ New York Morningside 1210 Amsterdam Ave, Mc 2205 New York, Ny 10027 Timing: Fiscal Year 2002; Project Start 01-JAN-2002; Project End 31-DEC-2006 Summary: (provided by applicant): This grant application describes a cell-based assay for detecting molecular recognition and catalysis that can be used to evolve proteins with new functions. There is tremendous interest in being able to engineer proteins with new specificities and new activities for use as reagents for biomedical research, diagnostics and therapeutics for the health care community, and tools for the pharmaceutical industry. The screen builds from existing technology for dimerizing proteins inside a cell with dimeric ligands via the ligands' receptors (CIDs). By replacing one of the ligand-receptor pairs with potential binding partners, binding can be detected. By replacing the chemical linker between the two ligands with a bond and adding an enzyme, the assay can be used as a read-out for bond formation or bond cleavage. In Preliminary Results dexamethasone-methotrexate CIDs with non-cleavable and cleavable linkers have been developed. Aim 1 outlines our plans to evolve a protein receptor for estradiol that can be used in medical diagnostics for monitoring estrogen levels in women. We have developed a docking algorithm to pick several monomeric proteins from the PDB as the starting protein scaffolds. We plan to mutagenize these proteins using existing methods and then select for high affinity, specific receptors by screening for binding to estradiol and against binding to other common steroids. Aim 2 describes our plans to modify the yeast two-hybrid assay to detect catalysis and then evolve a penicillin-binding protein into a cephalosporinase enzyme. Penicillin-binding proteins are the target of penicillin antibiotics and are believed to be the evolutionary precursors of cephalosporinases, the bacterial resistance enzymes that hydrolyze and inactivate these antibiotics. Because of the evolutionary relationship, the PBPs present a tractable first target for enzyme evolution. Moreover, this project should provide insight into how bacteria evolve antibiotic resistance and the mechanism by which the 2
Healthcare projects are funded by the National Institutes of Health (NIH), Substance Abuse and Mental Health Services (SAMHSA), Health Resources and Services Administration (HRSA), Food and Drug Administration (FDA), Centers for Disease Control and Prevention (CDCP), Agency for Healthcare Research and Quality (AHRQ), and Office of Assistant Secretary of Health (OASH).
Studies
5
resistance enzymes hydrolyze the antibiotic. Finally, in Aim 3, we propose to develop a bacterial CID so that future protein evolution experiments can be carried out in bacteria. Bacteria have faster doubling times and higher transformation efficiencies than yeast, and so a bacterial CID system should facilitate the evolution experiments. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •
Project Title: ADRENAL ANDROGEN EXCESS IN THE POLYCYSTIC OVARY SYNDROME Principal Investigator & Institution: Azziz, Ricardo; Professor and Chairman; Obstetrics and Gynecology; University of Alabama at Birmingham Uab Station Birmingham, Al 35294 Timing: Fiscal Year 2002; Project Start 01-MAY-1993; Project End 31-AUG-2002 Summary: Adrenal androgen (AA) production is frequently abnormal in women with hyperandrogenic oligoovulation (HO). A number of investigators, including ourselves, have noted that AA excess may result from a generalized adrenocortical hyperreactivity to adrenocorticotropic hormone (ACTH) or pituitary overresponse to corticotropin releasing hormone (CRH). This adrenocortical dysfunction may represent an acquired defect secondary to excessive ovarian secretion of androgens, such as testosterone. Alternatively, the dysfunction may represent an inherited abnormality, such as heterozygosity for 21-hydroxylase (21-OH) deficiency. Regardless of the etiology, the significance of AA excess in the maintenance of ovulatory dysfunction in HO is unclear. The Specific Aims of the proposal include: 1) to establish the sensitivity and responsivity to ACTH and CRH in HO patients with and without adrenocortical dysfunction; 2) to establish the role of ovarian factors in the development/maintenance of adrenocortical dysfunction; 3) to establish the role of mild inherited defects in adrenal 21-OH function in the development of HO; 4) and to establish the role of AA excess in the maintenance of ovulatory dysfunction in HO patients, while elucidating endocrine markers for a favorable response to corticosteroid suppression. To achieve Specific Aim 1 the adrenocortical sensitivity and responsivity to incremental doses of ACTH, and to ovine CRH, will be determined in 10 HO patients with and 10 without adrenocortical hyperreactivity, and in 10 control women. For Specific Aim 2 ten HO patients with and 10 without adrenocortical dysfunction will undergo three months of ovarian suppression using a long-acting GnRH-a, and alterations in basal androgen profiles, response to ovine CRH and ACTH, and glucose tolerance will be assessed. For Specific Aim 3 at least 30 females who are obligate heterozygotes for 21-OH deficiency will be studied for the presence of HO. To achieve Specific Aim 4 at least forty consecutive patients presenting with HO will be treated with three months of dexamethasone (0.5 mg/day), and their clinical response correlated with various adrenocortical markers. These studies will shed light on the etiology and role of adrenocortical of HO. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen
•
Project Title: ADRENAL REGENERATION: STEM CELLS AND LINEAGE DEVELOPMENT Principal Investigator & Institution: Breault, David T.; Children's Hospital (Boston) Boston, Ma 021155737 Timing: Fiscal Year 2004; Project Start 01-JUL-2004; Project End 30-JUN-2009 Summary: (provided by applicant): A number of disease states arise from the loss or destruction of tissue, e.g., loss of pancreatic islets cells results in Type I Diabetes and loss of adrenal cortical cells results in Addison's Disease. The ultimate treatment of these
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Dexamethasone
conditions would involve (1) reversal of the destructive process and (2) restoration of normal tissue. Tissue regeneration is the process by which lost or damaged tissue is restored to its normal state. The mechanisms, which regulate this dynamic and essential process, remain incompletely understood. Two major mechanisms include the regulation of (1) tissue-specific adult stem cells and (2) lineage development, which likely involves cellular differentiation, de-differentiation and trans-differentiation. Employing a classic model of tissue regeneration, the mouse adrenal cortex, we will investigate these fundamental processes. Using fluorescence activate cell sorting, we will identify, isolate and characterize adrenal progenitor cells from animals undergoing a variety of controlled manipulations. Progenitor cells will then be examined for their differentiation potential in transplantation model systems. Using a gene targeting approach and Cre-LoxP technology we will genetically modify mouse adrenal cells in order to perform lineage tracing and tissue-specific knockout experiments. These experiments are designed to elucidate fundamental mechanisms of adrenal development and zonation and begin to define the molecular pathway of adrenal regeneration. This work is being performed in a highly supportive environment with expertise in each major area proposed for study. Furthermore, this work builds upon the prior experiences of the PI, generating transgenic animals to study gene expression and lineage development, by incorporating the modern tools of gene targeting and Cre-LoxP technology. Finally, by combining this work with limited clinical responsibility (10% time) as a Pediatric Endocrinologist, the PI will continue to benefit from clinical encounters, which often lead to novel insights into the mechanisms of disease. It is expected that this work will be enable the PI to transition to a career as an independent researcher. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •
Project Title: ALCOHOL AND GENDER EFFECTS ON STRESS CIRCUIT FUNCTION Principal Investigator & Institution: Anthenelli, Robert M.; Associate Professor of Psychiatry; Psychiatry; University of Cincinnati 2624 Clifton Ave Cincinnati, Oh 45221 Timing: Fiscal Year 2003; Project Start 01-SEP-2003; Project End 31-AUG-2008 Summary: (provided by applicant): Women and men differ in the ways stress affects the development and maintenance of alcoholism. However, no published studies in alcohol dependent patients have examined sex differences in stress responsiveness that most likely mediate these effects and influence the clinical course and treatment of the disorder. This revised application proposes to extend our preliminary work revealing sex-dependent alterations in basal and serotonin-induced stress responses in abstinent alcoholics. Serotonin regulates the brain's response to certain uncontrollable stressors, and there are sex differences in both serotonin and hypothalamic-pituitary-adrenal (HPA) function. Thus, our chief aim is to determine whether the hypersensitive and prolonged stress response we observed in female alcoholics is related to sex differences in serotonin signaling or HPA sensitivity. Our central hypothesis is that sex differences in serotonin function or HPA sensitivity conspire with genetically influenced alterations in serotonin signaling to produce maladaptive stress responses in some alcoholic women. To test this hypothesis, we will perform a randomized, double blind, crossover study where subjects receive provocative tests with citalopram, dexamethasone/corticotropin-releasing hormone and placebo on 3 separate, counterbalanced occasions at monthly intervals. Subjects will be verified abstinent, treatment seeking alcoholic women and men without comorbid psychiatric or other illicit substance use disorders residing in controlled sober living environments. Non-
Studies
7
alcoholic women and men will serve as controls, and all groups will be balanced on the number of subjects with and without a family history of alcoholism. Subjects' DNA will be genotyped to determine allelic variants in the promoter region of the serotonin transporter gene that have been found to influence transporter function and stress responsiveness. Endocrine, behavioral, cardiovascular and catecholamine stress measures will be obtained along with measures of life stress and adverse life events that may influence the outcome measures. To our knowledge, this will be the first study conducted in alcohol dependent patients to simultaneously assess biological sex differences in stress responsivity, gender differences in environmental life stress, and the serotonin transporter polymorphism. The results should advance the field by identifying mechanisms underlying sex differences in stress responsiveness that influence vulnerability to develop alcoholism and responsiveness to serotonergic medications intended to prevent or treat the disorder. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •
Project Title: ANGIOGENESIS AND THALIDOMIDE THERAPY IN MULTIPLE MYELOMA Principal Investigator & Institution: Rajkumar, S Vincent.; Mayo Clinic Rochester 200 1St St Sw Rochester, Mn 55905 Timing: Fiscal Year 2002; Project Start 15-APR-2002; Project End 31-MAR-2005 Summary: (Provided by applicant): Angiogenesis is increased in multiple myeloma (MM) and has prognostic value. The anti-angiogenic agent, thalidomide, is effective in refractory MM and has shown marked synergy with dexamethasone. A randomized multi-institutional ECOG study will compare thalidomide plus dexamethasone versus dexamethasone alone in newly diagnosed MM. This proposal will utilize blood and bone marrow (BM) samples from this important study to test the central hypothesis that angiogenesis is important in MM and that anti-angiogenic therapy will be an effective way to treat MM. Preliminary data indicate that thalidomide can lead to decreased BM angiogenesis and VEGF expression. We hypothesize that thalidomide decreases the expression of VEGF and its receptors and inhibits BM angiogenesis, resulting in increased plasma cell apoptosis, decreased proliferation and tumor response. We also have data that support our hypothesis that thalidomide plus dexamethasone can inhibit mesenchymal progenitor cell (MPC) cytokine expression and differentiation. The proposal is organized into 3 specific aims: 1) To compare changes in BM angiogenesis and the level of expression of VEGF and its receptors before and after therapy and to correlate these measurements with response to therapy. 2) To determine the relationship between BM angiogenesis and MM cell VEGF expression with rates of myeloma cell apoptosis and proliferation and 3) To determine if thalidomide therapy inhibits expression of angiogenic cytokines/growth factors by BM MPC's and restores normal BM MPC function. For all 3 aims, our hypothesis is that the effects will be more pronounced with thalidomide plus dexamethasone than with dexamethasone alone. BM angiogenesis will be studied using immunohistochemical staining for CD34 and the rat aortic ring assay. Immunohistochemistry, in-situ hybridization, ELISA and RT-PCR assays will be used for the study of VEGF and its receptors and MPC cytokine expression. MPC growth and differentiation will be studied and compared to normal controls. Apoptosis will be measured using flow cytometric assays that gate on tumor cells; plasma cells in S-phase and circulating plasma cells will be estimated using slide based immunofluorescent assays. This study offers a unique opportunity to serially study tumor cells and the tumor microenvironment following potential anti-angiogenic therapy.
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Dexamethasone
Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •
Project Title: ANTI APOPTOTIC SIGNALING IN MYELOMA--BCL 2 AND NF KAPPA Principal Investigator & Institution: Feinman-Siegel, Renata R.; Surgery; Univ of Med/Dent Nj Newark Newark, Nj 07103 Timing: Fiscal Year 2002; Project Start 01-APR-2000; Project End 31-MAR-2004 Summary: Understanding the molecular mechanisms by which myeloma cells evade signals leading to chemotherapy-induced apoptosis is the long term goal of this project. Glucocorticoids such as dexamethasone (Dex], all potent inducers of apoptosis are frequently used to treat multiple myeloma [MM], a clonal B cell-malignancy. Using standard doses of these agents, complete remissions are rare [5% of patients]. Drug resistance increases with prolonged treatment, suggesting primary resistance of tumor cells as a major obstacle to cure. This resistance maybe due to MM cell expression of moderate to high levels of the anti-apoptotic protein bcl-2. There is compelling evidence that bcl-2 imparts its anti-apoptotic signal by ducking and modulating the expression of genes critical for apoptosis, including transcription factors such as NF-kappaB. We hypothesize that chemoresistance in MM by bcl-2 requires activation of NF-kappaB. To investigate this hypothesis we will address the following specific aims: 1. Test whether persistent NF-kappaB activation observed in MM cells confers resistance in chemotherapy-induced apoptosis in MM cell lines. P50:p65 NF-kappaB subunits will be over-expressed in drug-sensitive MM cell lines to inactivated NF-kB. Antisense phosphorothiorate oligonucleotides for p50 and p65 will also be used to inhibit NFkappaB. 2. Determine whether bcl-2 contributes to maintaining NF-kappaB activity through modulation of drug-mediated post-translational regulation of IkappaB proteins and/or p65 transactivation. Different modes of IkBalpha, Ikbeta and Ikepsilon protein regulation will be investigated: 1] basal and signal-induced IkappaB phosphorylation and degradation 2) IKK-alpha and -beta functions and 3) inhibitory properties of IkappaB proteins. For p65 transactivation: 1] a Gal4-BASED hybrid system will be used to test whether clinically relevant drugs and enforced bcl-2 interfere with the transactivation potential of p65 and 2] a bcl-2 deletion mutant that lacks the transmembrane domain will be expressed in MM cell lines to determine whether membrane-anchored bcl-2 augments p65 transactivation. 3. Investigate whether the inhibitory effects of Dex on NF-kappaB activity predict response to chemotherapy. Longitudinal studies will be conducted to determine whether patient responsiveness to glucocorticoid based therapy can predicted from their in vitro response to Dex in terms of NF-kappaB DNA binding, p65 immunostaining. There studies will hopefully provide deeper insight into the molecular basis of drug resistance in MM and should result in the identification of potential targets for therapeutic intervention. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen
•
Project Title: ANTI-INFLAMMATORY CONSTITUENTS
PROPERTIES
OF
CANNABIS
Principal Investigator & Institution: Zurier, Robert B.; Professor; Rheumatology; Univ of Massachusetts Med Sch Worcester Office of Research Funding Worcester, Ma 01655 Timing: Fiscal Year 2003; Project Start 15-SEP-2003; Project End 31-MAY-2005 Summary: (provided by applicant): The overall long term objective of this proposal is to determine whether individual nonpsychoactive constituents of Cannabis sativa (marijuana), alone or in combination, will provide safe, effective treatment for diseases
Studies
9
characterized by acute and/or chronic inflammation. The medicinal use of marijuana has been limited by its psychoactivity and by induction of tolerance. Existence of nonpsychoactive marijuana constituents and development of synthetic cannabinoids encourage further research to identify nonpsychoactive plant components with antiinflammatory properties. A complete marijuana extract (CME) and pure nonpsychoactive cannabinoid and noncannabinoid Cannabis constituents will be tested in human whole blood models for their ability to influence production in vitro of inflammatory eicosanoids and cytokines. The antiinflammatory effects of oral administration of the CME and the pure nonpsychoactive Cannabis constituents will also be tested in a model of acute inflammation (induced by IL-1Beta and TNFalpha in a subcutaneous air pouch in rats), and a model of chronic inflammation (adjuvant induced polyarthritis in rats). Controls for experiments in vitro and studies in animals will include vehicle, dexamethasone, indomethacin, and a selective inhibitor of cyclooxygenase 2. A noncannabinoid, nonpsychoactive marijuana constituent termed cannflavin will be isolated using high-pressure liquid chromatography and tested in the in vivo models and in vitro systems. Successful completion of the proposed experiments should identify ways of harnessing important antiinflammatory properties of marijuana without the limiting adverse effects. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •
Project Title: MENINGITIS
BIOACTIVITIES
OF
PNEUMOCOCCAL
CELL
WALL
IN
Principal Investigator & Institution: Tuomanen, Elaine I.; Chair, Professor; St. Jude Children's Research Hospital Memphis, Tn 381052794 Timing: Fiscal Year 2002; Project Start 01-JUN-1989; Project End 31-JAN-2005 Summary: The pneumococcus remains the cause of meningitis with the greatest morbidity and mortality in children and older adults. This pattern persists despite the use of antibiotics of exceptionally rapid bactericidal activity. Over the past 10 years of this proposal we have sought to understand the biochemical basis of the inflammatory response to pneumococci in the subarachnoid space. We established that the pneumococcal cell wall is a library of inflammatory components which incites the cytokine, coagulation and arachidonate cascades and directly injures endothelial cells of the blood brain barrier. Further, we established that the release of cell wall during antibiotic-induced death engenders a dramatic host response that is responsible for serious injury to host tissues. This provided a rationale for use of agents like dexamethasone that can act as partner drugs with antibiotics to selectively control the injurious components of the host defense response. The current proposal seeks to determine the molecular details of the mechanism of pneumococcal invasion into brain and how neuronal cells are killed during meningitis. Blocking information decreases some sequelae of infection but does not appear to be sufficient in controlling neuronal loss, particularly for pneumococcal disease. Over half of the current survivors of this injection still have major permanent sequelae. Understanding this process will allow design of agents to specifically attenuate these ongoing losses. We propose to apply our expertise in the identification and characterization of pneumococcal surface components, to map the process of transcytosis across the blood brain barrier. We will identify the pneumococcal components involved, specifically focusing on CbpA. This protein is required for pneumococcal invasion. Secondly, we will characterize the process of pneumococcal translocation in terms of the intracellular vesicle and the signaling process. Involvement of the PAF receptor that binds pneumococci and sIgA that ligates CbpA in actual translocation will be determined. Finally, we will investigate
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preliminary evidence that upon inhibition of apoptosis suggest this is an important contributor to sequelae. The detailed mechanism appears to be novel and will potentially instruct cell biology as well as pathogenesis. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •
Project Title: BIPOLAR DISORDER & ALCOHOL ABUSE COMORBIDITY Principal Investigator & Institution: Frye, Mark A.; Psychiatry & Biobehav Sciences; University of California Los Angeles 10920 Wilshire Blvd., Suite 1200 Los Angeles, Ca 90024 Timing: Fiscal Year 2003; Project Start 16-AUG-2001; Project End 31-JUL-2007 Summary: The applicant proposes to acquire new training in magnetic resonance spectroscopy and neuroendocrinology. These two areas of investigation will expand his clinical research expertise and further his research endeavors in attempting to better understand the neuroanatomic and neuroendocrinological underpinnings of bipolar disorder. The research training will then be used to translate these potential research gains into clinical applications to better understand and ultimately treat major psychiatric illnesses. This study will examine the impact of alcohol on the biochemistry, neuroendocrinology, and neuropsychological functioning of bipolar illness. The lifetime prevalence rate of alcohol abuse comorbidity in bipolar disorder is the highest of all Axis I diagnoses; furthermore, the presence of alcohol abuse in bipolar disorder is associated with a decreased response rate to the gold standard treatment lithium carbonate. Thus, by prevalence data and inadequate treatment response, this represents an enormous public health problem. In a cross-sectional analysis, patients with bipolar disorder and comorbid alcohol abuse or dependence, patients with bipolar illness without comorbid alcohol abuse or dependence, and age matched healthy controls will undergo 1 H-MR spectroscopy, Dexamethasone/CRH neuroendocrine challenge, and neuropsychological evaluation assessing executive function, verbal memory, and working memory. This study will evaluate whether there are differences amongst the three groups and if there is a relationship between N-acetylaspartate (NAA), hypothalamic-pituitary adrenal axis function, and neuropsychological functioning. These variables will also be evaluated as to their predictive potential for relapse under naturalistic follow-up where mood stability, alcohol craving and relapse, medication compliance, and functional capacity will be monitored. This naturalistic follow-up period may identify preliminary neurobiological factors associated with relapse and provide direction for further controlled interventional study. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen
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Project Title: BR22, A NOVEL PROTEIN INTERACTING WITH TTF-1 Principal Investigator & Institution: Yang, Yih-Sheng; Internal Medicine; University of Texas Sw Med Ctr/Dallas Dallas, Tx 753909105 Timing: Fiscal Year 2002; Project Start 01-APR-2002; Project End 31-MAR-2006 Summary: (provided by applicant): Surfactant is a mixture of lipids and proteins on the alveolar surface that plays an important role for gas exchange. Surfactant protein B (SPB), an important protein component of surfactant, is expressed in type II cells and Clara cells in the lung. SP-B expression is mainly controlled by thyroid transcription factor-1 (TTF-1) and hepatocyte nuclear factor-3. Previously, we uncovered a novel polypeptide, BR22, a TTF-1 associated protein (m. wt. 26 kD) (TAP26), which bound to human SP-B promoter sequence at the proximal region containing TTF-1 binding sites and interacted with TTF-1 to activate SF-B promoter. This protein also exhibits a direct protein-protein
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contact with TTF-1 in vivo and in vitro. In this proposal, we will demonstrate that TAP26 is a co-factor of TTF-1 to regulate the SP-B promoter activity in the lung. In order to understand the mechanism by which TAP26 modulates the promoter activity, the following approaches will be performed: 1) Characterize the contact domain modules of TAP26 and TTF-1 for a better understanding of the detailed protein complex structure. Deletion and mutagenesis analyses will be employed for the characterization. 2) Determine the mechanism by which TAP26 acts with TTF-1 to modulate the SP-B promoter activity. TAP26 in H441 cells will be sequestered to demonstrate its influence on the promoter activity. In addition, the effect of dexamethasone, cAMP, and phorbol ester on SP-B promoter activity will be inspected in the absence of TAP26 to determine if the regulation is mediated through TAP26. 3) Establish the relationship between TAP26 and SPB expression. The amounts of TAP26 message and protein level will be evaluated under conditions in which the SF-B expression is altered in vivo. 4) The DNA-binding activity of TAP26 and TAP-26/TTF-1 complex on the SP-B promoter will be inspected. The association of this protein complex and SP-B promoter in vivo will be examined by chromatin cross-linking and immunoprecipitation (CHIP) analysis. 5) Inspect cellular locations of TAP26 and TTF-1 in lung cells expressing SF-B. Two-color or triple-color staining of endogenous proteins in H441 cells or the lung sections will be performed to detect their expression in SP-B producing cells. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •
Project Title: C REACTIVE PROTEIN IN HOST DEFENSE Principal Investigator & Institution: Szalai, Alexander J.; Medicine; University of Alabama at Birmingham Uab Station Birmingham, Al 35294 Timing: Fiscal Year 2002; Project Start 01-FEB-1998; Project End 31-JAN-2003 Summary: (Adapted from applicant's abstract): C-Reactive Protein transgenic (CRPtg) mice mount acute phase human CRP responses, which protect against lethal infection with pneumococci. The long term objective of the proposed research is to define the mechanisms for this CRP-dependent host defense function. Our working hypotheses are: 1) CRP contributes to pre-immune host defense by binding to pathogens, thus targeting them for clearance via complement activation and Fc receptor (FcR)-mediated phagocytosis. 2) Activation of complement by CRP leads to deposition of C3 fragments on bacteria, leading to enhanced protective antibody responses. A similar effect is mediated by CRP-coated antigens binding to FcR on antigen-presenting cells. 3) These events depend on rapid induction of the CRP gene, in proportion to the levels of its hormonally-regulated constitutive expression. These hypotheses will be tested using CRPtg mice and their hybrids genetically deficient in the complement proteins C3 and factor B, in the ^H-chain of FcR, and in interleukin-6. The extent of protection from pneumococci, meningococci, and salmonellae, effected by serum CRP and CRP present in the lungs, will be determined. Model thymus-dependent and -independent antigens will be used to investigate the effects of CRP on the anti-bacterial antibody response. Finally the role of sex hormones, dexamethasone, growth hormone, and complement protein fragments in CR gene regulation will be investigated. These studies will increase the understanding of innate host defense mechanisms and their interaction with acquired immunity. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen
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Project Title: CANDIDA PATHOGENESIS IN SURGERY AND TRAUMA Principal Investigator & Institution: Wells, Carol L.; Professor; Lab Medicine and Pathology; University of Minnesota Twin Cities 200 Oak Street Se Minneapolis, Mn 554552070 Timing: Fiscal Year 2004; Project Start 01-DEC-2003; Project End 30-NOV-2007 Summary: (provided by applicant): Candida species are the fourth most common cause of nosocomial blood stream infections, and C. a/bicans accounts for 50% to 75% of Candida species in essentially all studies. Despite appropriate antifungal therapy, mortality is 35% to 75%. Patients at highest risk include immunosuppressed patients, trauma patients, and postsurgical patients, and a large proportion of cases occur in intensive care units. C. a/bicans undergoes reversible morphologic switching, producing budding yeast and filamentous forms that include germ tubes, pseudohyphae and true hyphae. Many investigators have assumed that filamentous forms are responsible for epithelial invasion. However, recent data from mouse models of extraintestinal dissemination indicate that the yeast cell, rather than filamentous forms, might be more important in C. a/bicans penetration of intestinal epithelium. Our working hypothesis is that yeast cells play a key role in interactions (adherence and penetration) of this fungus with the intestinal epithelium. The general approach is to use wild type and well-characterized C. albicans mutant strains (with defects in morphologic switching) to challenge this hypothesis in vitro (cultured enterocytes) and in vivo (mouse models). Because C. glabrata has recently emerged as the second most frequent cause of candidiasis, and because C. glabrata is the only species (of the more than 80 recognized Candida species) that does not form filaments and exists only in the yeast form, experiments also focus on C. glabrata. In vitro experiments are designed to separately characterize the interactions (adherence, internalization, intracellular survival) of yeast and filamentous forms with cultured enterocytes, and assay systems include ELISA and a double fluorochrome assay using calcoflour and the vital dye FUN1. Mouse models include antibiotic-induced intestinal Candida colonization, ligated intestinal loops, and the Stamper-Woodruff assay. The effect of bacterial cell wall products (lipopolysaccharide and peptidoglycan), dexamethasone, and hypoxia on extraintestinal dissemination of Candida is also clarified. If our hypothesis is validated (that the yeast cell is of primary importance in extraintestinal dissemination), then efforts to design more effective in vitro susceptibility assays, as well as more effective prophylactic and therapeutic modalities, might more reliably target yeast rather than hyphal elements. Such knowledge should accelerate our ability to diagnose, treat, and control systemic candidiasis. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen
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Project Title: CELLULAR MECHANISMS OF MATRIX REGULATION IN LIVER REPAIR Principal Investigator & Institution: Tracy, Thomas F.; Rhode Island Hospital (Providence, Ri) Providence, Ri 02903 Timing: Fiscal Year 2002; Project Start 01-MAY-1994; Project End 31-JUL-2007 Summary: (provided by applicant)At critical points in chronic liver injury the potential for liver repair is lost. Timely surgical and medical treatment however, initiates liver repair interrupting the cycle of inflammation and hepatic fibrosis. The subsequent cellular regulation of matrix protein degradation and resolution of injury dependent fibrosis is unknown. The long-term goals of our studies are to define the molecular mechanisms required for ordered matrix resorption and liver repair without scar.
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Specific aims have been designed to test the hypothesis that repair, resolution of scar, and the restoration of hepatic architecture depend on coordinated regulatory mechanisms of matrix degradation through matrix metalloproteinase (MMP) and tissue inhibitor of MMP (TIMP) gene expression, cellular localization and most importantly, biologic activity. Further, we propose that Kupffer cells (KC), the resident macrophage population, have a central role in the inflammatory and fibrogenic regulation of liver repair after chronic injury. Specific Aim 1 addresses the molecular and cellular mechanisms of reversible hepatic fibrosis and those of delayed matrix resorption. A unique rat model of reversible biliary obstruction will simulate early, intermediate, and late, near end stage cholestatic liver injury. This model allows biliary decompression to initiate liver repair. [The effect of injury duration on key matrix (collagen I and III, laminin), MMP (1,2,8,9) and TIMP (1,2) mRNA and protein expression will be measured in whole liver and in [individual] cells using new methods of laser capture microdissection. [These data will demonstrate the mechanism and physiology of matrix resorption through measurement of MMP activity by in-gel and in-situ zymography]. Specific Aim 2 tests the hypothesis that KC are in vivo regulators of matrix metabolism. Through strategies of KC depletion/ inactivation by gadolinium or Dexa-Man10-HSA targeted dexamethasone during repair, matrix resorption, regulatory cytokine profiles and MMP-TIMP activity will be localized in cells and measured. In Specific Aim 3 we will establish the effect of progressive injury on the in vitro capacity of isolated hepatic macrophages (MPh) to express specific MMP and fibrogenic/ antifibrogenic cytokine (TGFbeta, IL1, 6, 10) profiles during repair. KC inactivation and MMP stimulation/ suppression strategies will isolate the net collagenolytic activity of MPh. [In addition to the broad clinical implications for the treatment of cholestatic or other chronic liver diseases in infants, children, and adults, these studies may be the first to identify key molecular mechanisms for successful repair after progressive liver injury. They have the unique potential to yield targets for therapy to promote liver repair or rescue patients approaching end stage liver disease Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •
Project Title: CEREBRAL 18FDG UPTAKE FOLLOWING HYDROCORTISONE IN PTSD Principal Investigator & Institution: Grossman, Robert A.; Psychiatry; Mount Sinai School of Medicine of Nyu of New York University New York, Ny 10029 Timing: Fiscal Year 2002; Project Start 01-SEP-1999; Project End 31-AUG-2004 Summary: (Adapted from Applicant's Abstract): Dr. Robert Grossman received his M.D. from the Mount Sinai School of Medicine, was a resident at Cornell New York HospitalWestchester Division, completed an NIMH sponsored research fellowship in the neurobiology of trauma and personality, and has been an Assistant Professor of Psychiatry since July, 1996. Over the past 4 years he has been engaged in research of glucocorticoid and serotonin function in post traumatic stress disorder (PTSD) and borderline personality disorder with his mentors Rachel Yehuda, Ph.D. and Larry Siever, M.D. He has recently begun preliminary work in quantitative hippocampal neuroimaging in trauma-related disorders with Monte Buchsbaum M.D. Dr. Grossman's immediate career goals are to devote at least 75% of his time over the next five years to further conceptual and technical training in eruoendocrinology, structural, functional, and metabolic neuroimaging, and neuropsychological assessment of cognitive function. His intensive training program will include: 1) formal postgraduate coursework; 2) supervision and interaction with mentors, collaborators and scientific advisors; and 3) conduct of original research. Dr. Grossman's long-term career goals are to establish
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himself as an independent investigator within an academic psychiatry program in the area of central glucocorticoid-mediated effects on hippocampal volume and functioning. Two major findings in the field of PTSD research have been hypothalamic-pituitaryadrenal (HPA) axis alterations and smaller hippocampal volumes. Preclinical studies suggest that central glucocorticoid-mediated effects may be associated with these hippocampal abnormalities. In addition, the hippocampus is an important region (both structural and functionally) intimately involved in declarative memory. Dr. Grossman's broad aims are to investigate these relationships in PTSD. Dr. Grossmans's specific aims are to measure and correlates: 1) central glucocorticoid sensitivity utilizing a placebocontrolled hydrocortisone challenge followed by 18-FDG uptake and PET scanning; 2) peripheral HPA axis measures of cortisol negative feedback sensitivity to dexamethasone and plasma lymphocyte glucocorticoid receptors; 3) hippocampal volume using MRI; 4) neuropsychological deficits at baseline; and 5) alternations in declarative memory function following a hydrocortisone/placebo challenge. Subject groups will include PTSD subjects, traumatized subjects without PTSD, and health nontraumatized subjects. Animal studies have found flucocorticoid-mediated effects to include both hippocampal cell atrophy and death. These models have also demonstrated that particular interactions can prevent or reverse hippocampal atrophy. The results of these studies will likely have broad and important implications for the neuroscience's, and treatment implications in PTSD patients and perhaps other populations with HPA axis alterations and hippocampal findings such as Suching's disease, Alzheimer's disorder, and recurrent major depression. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •
Project Title: CHEMOPREVENTION IN MICE AFTER TOBACCO SMOKE EXPOSURE Principal Investigator & Institution: Witschi, Hanspeter R.; Professor, Associate Director; None; University of California Davis Sponsored Programs, 118 Everson Hall Davis, Ca 95616 Timing: Fiscal Year 2002; Project Start 01-APR-2002; Project End 31-MAR-2005 Summary: (provided by applicant): In former smokers, "suppressing" chemopreventive agents, i.e. agents which have chemopreventive activity when given after the carcinogen, would appear to most useful. We have established that strain A mice exposed for five months to tobacco smoke and then kept for another four months in air develop significantly more lung tumors than do animals kept in air. We further have shown that a diet containing a mixture of myoinositol (10 g/kg diet) and dexamethasone (0.5 mg/kg diet) successfully prevents lung tumor development in mice exposed to tobacco smoke. The chemopreventive regimen is even effective when the animals are fed the myoinositol-dexamethasone diet once they have been removed from the smoke atmosphere. Thus we have an animal model that mimics "former smokers" and where other suppressing chemopreventive agents or treatment modes may be evaluated. Since myoinositol is a food constituent with no known toxicity, it will be explored whether myoinositol alone, fed in the diet, will give chemoprevention to mice that have "quit" smoking. In a second series of experiments we will examine whether the topical administration to the tissues of the respiratory tract of other suppressing agents (budesonide- epigallocatechin gallate (EGCG), isotretinoin, or lovastatin) may increase their efficacy while at the same time reducing their potential systemic toxicity in mice previously exposed to tobacco smoke. Eventually, these preclinical studies in an animal model of "former smokers" will help to evaluate the potential usefulness and also
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possible dosage regimens of chemopreventive agents characterized by their suppressing action. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •
Project Title: VOMITING
CORTICOTROPIN-RELEASING
FACTOR
ROLE
IN
CYCLIC
Principal Investigator & Institution: Li, B U.; Children's Memorial Hospital (Chicago) Chicago, Il 606143394 Timing: Fiscal Year 2002; Project Start 15-AUG-2002; Project End 31-JUL-2005 Summary: (provided by applicant): Cyclic vomiting syndrome (CVS) is the most severe recurrent vomiting disorder in humans and is more prevalent than previously appreciated (1 in 50 school-aged children). Although the pathogenesis remains unknown, corticotropin-releasing factor (CRF) is a tenable candidate brain-gut neuroendocrine mediator of vomiting in CVS. CRF has a well-established role in inducing gastric stasis and vomiting in animals and its resulting behavioral, autonomic, endocrine effects resemble those clinical features seen in CVS. The model of CRFinduced emeses may explain the antiemetic utility of dexamethasone during chemotherapy-induced vomiting and migraine headaches. We hypothesize that systemic CRF levels and hypothalamic-pituitary-ad renal (HPA) axis activity are heightened during episodes of CVS and migraine headache especially in those who experience concomitant nausea and vomiting. To provide direct clinical evidence of involvement of CRF pathways in CVS and migraine, we will examine CRF and HPA axis activation (ACTH, cortisol, catecholamines) in subjects with CVS, migraine headaches and controls under three conditions including: 1) when well (i.e. in between episodes), 2) during acute episodes of cyclic vomiting or migraine headaches treated with a saline placebo, and, 3) during acute episodes of cyclic vomiting or migraine headaches in which CRF is treated by dexamethasone. Under each condition, we will establish the diurnal variation of CRF and HPA axis activity and compare them to pediatric controls, both healthy and with non-CVS vomiting (gastroenteritis). In a randomized, double blind, cross-over design, we will examine the effect of dexamethasone on CRF and HPA axis activity, objective signs and subjective GI and migraine headache symptoms. CVS and migraine headaches may ultimately both be disorders involving dysregulation of CRF pathways. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •
Project Title: DECIDUAL CELL/PLACENTAL INTERACTIONS Principal Investigator & Institution: Hunt, Joan S.; University Distinguished Professor; Anatomy and Cell Biology; University of Kansas Medical Center Msn 1039 Kansas City, Ks 66160 Timing: Fiscal Year 2002; Project Start 01-AUG-1989; Project End 31-JUL-2004 Summary: The recent discovery of TRAIL (TNF Related Apoptosis-Inducing Ligand, also known as Apo-2L), has generated considerable excitement among immunologists because of its involvement in down-regulation of the immune response and host defense against tumors. This powerful apoptosis-inducing cytokine has been identified in both humans and mice and is synthesized in many types of cells. Five receptors have been identified: two initiate a signal cascade culminating in apoptosis, two act as cell surface decoys and a fifth is a soluble receptor. Receptor display therefore dictates whether a cell lives or dies. TRAIL and its receptors are abundant at the maternal-fetal interface and are differentially expressed among placental cell lineages. The data
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acquired to date support the postulate that TRAIL is central to placental immune privilege and has multiple additional functions such as regulating placental growth, differentiation and function. We have designed four Specific Aims to investigate this postulate, as follows: (Aim 1) to establish (a) cell-specific expression of TRAIL and TRAIL-R in human and mouse placentas and trophoblast cell lines and (b) the biochemical and molecular characteristics of human and mouse placental TRAIL; (Aim 2) to investigate regulation of TRAIL and each of its receptors in human and mouse trophoblast cells by placental cytokines (IFN-gamma, TNFalpha), lipopolysaccharide, cAMP and dexamethasone; (Aim, 3) to establish the functions of trophoblast cell TRAIL, evaluating involvement in invasion, expression of cell adhesion molecules and matrix metalloproteinases, hormone synthesis, and, killing capacity and resistance to killing by TRAIL-bearing cells; (Aim 4) to assess potential polymorphisms in the human TRAIL, and TRAIL-R genes, which might influence reproductive success, in collaboration with Dr. C. Ober, University of Chicago. We expect the results of this research to have a major impact on our understanding of the molecular basis for cell-to-cell interactions at the maternal-fetal interface that could ultimately lead to more efficacious therapeutic approaches for improving fertility and reproductive performance in women. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •
Project Title: DISTRIBUTION INNERVATION
AND
ULTRASTRUCTURE
OF
DENTAL
Principal Investigator & Institution: Byers, Margaret R.; Research Professor; Anesthesiology; University of Washington Grant & Contract Services Seattle, Wa 98105 Timing: Fiscal Year 2002; Project Start 01-MAY-1979; Project End 31-JAN-2004 Summary: Dental innervation is still not fully understood concerning its variety of nerve fibers, their interactions with pulp and dentin in normal teeth, and the mechanisms that cause hypersensitive dentin, postoperative pain, and difficult anesthesia for inflamed teeth. There is important plasticity in expression of sodium channels in injured cutaneous sensory neurons, driven by neurotrophic factors, but it is not known whether similar events underlie persistent neuroplasticity and pain after tooth injury. Teeth are an excellent model tissue for studying neuroinflammatory interactions in the periphery and their effects on trigeminal nerves, the ganglion and the central nervous. Tooth injury also affects non-dental neurons in the ganglion, in the brain stem and sometimes in contralateral trigeminal neurons by mechanisms that in part depend on paracrine signalling by nerve growth factor. The Aims of this work are: (1) to determine the effects of specific types of tooth injury on sodium channel expression in dental neurons, neighboring uninjured trigeminal neurons and central neurons in relation to pain behavior, pulpal pathology and anti-inflammatory treatment, (2) to determine whether trigeminal sodium channel expression, pulpal reactions and behavior are affected in mutant mice that have altered neurotrophin mechanisms, and (3) to define the complexities of cells in the pulp, especially the odontoblast layer, in relation to expression of neurotrophins and calcium channels, in order to better understand the pulpal-nerve interactions in normal and injured teeth. We will use dental injury models in rats and mutant mice for analysis by behavioral testing, immunocytochemistry and in situ hybridization. There will be specific labeling of injured dental neurons by retrograde transport of fluorogold for comparison with uninjured labeled neurons. Our newly developed behavioral assays allow the characterization of pain periods in relation to pulpal and neural cytochemistry during anti-inflammatory treatment or in mutant mice. Our goal is to understand neuroinflammatory interactions in inflamed teeth in order to develop better treatments for dental pain.
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Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •
Project Title: EFFECTS OF CHINESE HERBAL MEDICINES ON ALLERGIC ASTHMA Principal Investigator & Institution: Li, Xiu-Min; Pediatrics; Mount Sinai School of Medicine of Nyu of New York University New York, Ny 10029 Timing: Fiscal Year 2002; Project Start 15-FEB-2002; Project End 30-NOV-2003 Summary: (provided by applicant): Allergic asthma is a major public health problem, and the morbidity and motility of asthma have increased in the last two decades, particularly in children. The need for safe and effective asthma treatment is greater than ever. Although millions of asthma patients in the US are currently using "herbal therapies," there is little information regarding the efficacy, safety or mechanism[s] of action of herbal anti-asthma formulas. It has been shown that allergic asthma is associated with elevation of serum IgE, airway inflammation and airway hyperresponsiveness (AHR) in both asthmatic patients and animal models. Th 2-type cytokines such as IL-4, IL-5 and IL-13 play a central role in the pathogenesis of allergic asthma. To investigate the effect of herbal interventions for asthma therapy, we evaluated effects of a Chinese herbal formula, MSSM-002, on allergic airway responses using a well-characterized murine model of asthma. MSSM-002, developed in our laboratory, is based on Ja Wai San Zi Tang, used in the China-Japan Friendship Hospital in Beijing, to treat asthma and bronchitis in children. We found that MSSM-002 treatment reduced late-phase AHR, eosinophilic inflammation, mucus production, and IgE and Th2 cytokine production. Suppression of late-phase AHR by MSSM-002 was comparable to that of the potent corticosteroid, dexamethasone, and significantly greater than three commercially available Ma-Huang-containing herbal products. These preliminary results suggest that MSSM-002 has potential as an effective and safe treatment for human asthma. The objective of this project is to further investigate the therapeutic and immunoregulatory mechanisms underlying these effects. We will evaluate whether MSSM-002 can reverse maximally severe AHR, and exert a long-term as well as an acute effect on AHR. We will rigorously control the quality of herbs and consistency of the herbal formula using reproducible analytic methods such as HPLC and TLC, and further assess any possible toxicity utilizing histological and biochemical analyses. Based on our preliminary results, we hypothesize that, in contrast to the generalized immunosuppression produced by corticosteroids, MSSM-002 has specific immunomodulatory effects down-regulating the Th2 response and/or up-regulating the Thl response, which may underlie the observed reduction of AHR and inflammation by MSSM-002. We will further investigate the effects of MSSM-002 on in vivo and in vitro T cell cytokine production. We further hypothesize that MSSM-002 may exert beneficial regulatory effect on co-stimulatory molecules such as B7-1/B7-2 by antigen-presenting cells, which may be the upstream mechanisms of MSSM-002 regulating T cell responses. To move our study one step closer to human studies, we also plan to test the in vitro effects of MSSM-002 on human T cell responses. Accomplishing these goals should provide an experimental basis for applying Chinese herbal medicines to the treatment of allergic asthma, and for understanding immunoregulatory mechanisms underlying their effects. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen
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Project Title: ENVIRONMENTAL TEMPERATURE, SNS DEVELOPMENT AND OBESITY Principal Investigator & Institution: Young, James B.; Medicine; Northwestern University Office of Sponsored Research Chicago, Il 60611 Timing: Fiscal Year 2002; Project Start 01-JUL-1977; Project End 31-MAR-2006 Summary: (Scanned from the Applicant's Description): The long-term goal of this project is to determine how environmental exposures during development contribute to the acquisition of obese or hypertensive traits in the adult. If successful, it may be possible to devise strategies for early intervention which might prevent or at least forestall the development of these disorders. The studies proposed in this application address the lasting influence of several environmental factors during fetal and neonatal life (environmental temperature, maternal diet and prenatal exposure to glucocorticoids) on an animal's susceptibility to become obese as an adult. It is the contention of the applicants that these three exposures induce different obesity-prone phenotypes by altering specific aspects of sympathoadrenal function, along with possible increases in food intake. The applicants propose that early exposure to cool environmental temperatures will predispose animals to develop obesity without features of the so-called 'metabolic syndrome', while maternal ingestion of a synthetic diet will predispose similar animals to develop obesity along with the 'metabolic syndrome'. The applicants also predict that prenatal exposure to glucocorticoids will exacerbate any other tendencies in the offspring to develop the 'metabolic syndrome' in conjunction with obesity. Furthermore, since these exposures are not mutually exclusive of one another, the applicants propose that maternal exposure both to glucocorticoids and to a synthetic diet will interact synergistically to exaggerate tendencies in the offspring toward obesity and the 'metabolic syndrome'. In addition, since the brainstem locus for sympathetic premotoneurons to brown fat in raphe pallidus (RPa) may also contribute to regulation of glucose metabolism, it is hypothesized that activation or inhibition of RPa will produce corresponding changes in glucose disposal. The applicants propose to use techniques of norepinephrine (NE) turnover and urine catecholamine levels to assess sympathetic and adrenal medullary function, respectively, in unanesthetized animals and to utilize neurophysiological studies of impulse traffic in sympathetic fibers of anesthetized rats to examine the importance of RPa in mediating SNS activation by specific stimuli, such as insulin and leptin. The potential impact of changes in sympathetic activity regulated by RPa for glucose and energy metabolism will also be examined. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen
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Project Title: EXERCISE FIBROMYALGIA
INDUCED
CHANGES
IN
HPA
ACTIVITY
IN
Principal Investigator & Institution: Deuster, Patricia A.; Henry M. Jackson Fdn for the Adv Mil/Med Rockville, Md 20852 Timing: Fiscal Year 2002; Project Start 15-SEP-1999; Project End 31-AUG-2004 Summary: Five to 10 percent of patients entering general practice centers report symptoms of fibromyalgia syndrome (FMS), a painful and debilitating condition of the musculoskeletal system. Although the cause(s) and pathophysiology of this disorder are poorly understood, FMS has been referred to as a syndrome of physical deconditioning and involves dysregulation of the hypothalamic- pituitary-adrenal (HPA) axis. Interestingly, regular exercise has been shown to confer benefit for some patients with FMS, as well as rheumatoid arthritis and depression. Importantly these health
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conditions all have the common element of reduced hypothalamic drive for pituitary adrenal function. Thus, exercise may confer benefit in FMS by upregulating hypothalamic drive to the pituitary and adrenal glands. The overall objective of this proposal is to determine whether aerobic training benefits FMS by inducing alternations in HPA axis regulation. The central hypothesis is that aerobic training serves to enhance hypothalamic drive, and thus pituitary-adrenal function. Specifically, 20 patients with FMS and 20 age-, gender-, weight-matched controls will be challenged at baseline; after 12 weeks with no intervention (control), and after 12 weeks of aerobic conditioning to evaluate whether aerobic training results in: (1) An increase in hypothalamic drive as evidenced by augmented adrenocorticotropin (ACTH) responses to a standardized exercise test (SET); (2) An increase in tonic and stimulated hypothalamic drive as evidenced by augmented ACTH responses following administration of metyrapone and dexamethasone (DEX) coupled with SET; (3) An increase in hypothalamic-pituitary responsiveness as evidenced by augmented ACTH responses stimulated by a bolus of ovine corticotropin releasing hormone (o-CRH) after pretreatment with DEX; and (4) Improved clinical and psychological profiles in FMS. Plasma ACTH will be used to assess hypothalamic drive during four challenge tests: (a) SET for control stimulation; (b) SET during enhancement of glucocorticoid negative feedback by DEX; (c) tonic and SET during attenuation of glucocorticoid negative feedback by metyrapone; and (d) responsivity of pituitary corticotropes following a bolus of o-CRH during enhancement of glucocorticoid negative feedback by DEX. Finally, disease activity (tender point index, tender point score, and myalgic score), and self-reported physical measures of function, depression and self efficacy will be used to assess clinical and psychological profiles over the course of the study. The information gained will provide an understanding of the pathology of FMS and the mechanisms by which exercise confers benefit in FMS. Given the important role exercise serves in the prevention of disease, this information will also contribute to our basic knowledge regarding how exercise modulates HPA axis reactivity in health and, in so doing suggest, mechanisms for HPA dysregulation in disease. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •
Project Title: EXPERIMENTAL MODEL PREMATURITY
FOR CHORIOAMNIONITIS
AND
Principal Investigator & Institution: Gravett, Michael G.; Chief; None; Oregon Health & Science University Portland, or 972393098 Timing: Fiscal Year 2002; Project Start 01-SEP-1997; Project End 31-MAY-2006 Summary: Prematurity is the leading cause of neonatal morbidity and mortality in the United States. Intrauterine infections are an important, and potentially treatable cause of prematurity, and are associated with increased risk of neonatal white matter lesions of the brain and cerebral palsy. However, the mechanisms by which infection leads to prematurity and/or cerebral palsy remain speculative and treatment strategies untested largely because humans cannot be longitudinally studied following infection. We propose to use chronically instrumented pregnant rhesus monkeys at 120-130 day gestation with experimental intrauterine infection, as previously described (Gravett et al, Am J Obstet and Gynecol; 171:1660-1667,1994) to study the temporal and quantitative relationships among infection, cytokines, prostaglandins, steroid hormones, cytokine antagonists, preterm labor, and neonatal white matter lesions of the brain in order to develop effective interventional strategies. After postoperative stabilization in a tether, we will; (1) inoculate Group B Streptococci (GBS) into the amniotic fluid to establish intrauterine infection and preterm labor. Uterine contractility will be continuously
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monitored and periodic samples of amniotic fluid and maternal and fetal blood (1-4 cc) will be obtained for assays of eicosanoids, steroid hormones, cytokines, matrix metalloproteinases and for microbial studies; (2) utilize antibiotics with and without potent inhibitors of proinflammatory cytokine production (dexamethasone,IL-10) o prostaglandin production (indomethacin) to ascertain the most effective intervention to down-regulate the cytokine/prostaglandin cascade and associated uterine activity; (3) infuse proinflammatory cytokine IL-1beta into the amniotic cavity through indwelling catheters in the absence of infection. Prior to infusion of IL-1beta in the absence of infection, specific novel proinflammatory cytokine inhibitors (IL-1ra and sTNF-R1 PEG) will be used to identify other potentially useful immunomodulators. Samples of the decidua, fetal membranes, tissues, and brain will be obtained at cesarean section for microbiologic, histopathologic studies, immunohistochemistry for cytokines, localization and quantitation of mRNA for cytokines and PGHS-2. Fetal brain will be examined for increased apoptosis associated with white matter lesions. Leukocytes in amniotic fluid and tracheal aspirates will be assessed by flow cytometry Postpartum, the mother will be treated with appropriate antibiotics to eradicate the GBS from the genital tract and returned to the colony. These studies will clarify the pathophysiology of infection-associated preterm labor and will suggest effective interventional strategies. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •
Project Title: EXTRACELLULAR MATRIX ABNORMALITIES IN CORNEAL EDEMA Principal Investigator & Institution: Kenney, Maria C.; Director,Molecular Eye Reseach Lab.; Ophthalmology; University of California Irvine Irvine, Ca 926977600 Timing: Fiscal Year 2002; Project Start 01-AUG-1995; Project End 31-JUL-2004 Summary: (Adapted from applicant's abstract): Pseudophakic (PBK) and aphakic (ABK) bullous keratopathy is the most common indication for corneal transplantation. The investigators have showed that in PBK/ABK corneas, there is an increased expression and deposition of specific isoforms of an extracellular matrix protein, tenascin-C (TN-C), that is not expressed in normal corneas. TN-C can affect cell adhesion, migration and proliferation that are important in wound healing and tissue remodeling. They have also shown that PBK/ABK corneas have a corresponding increase in the expression of TN-C integrin receptors and certain growth factors/cytokines, which could induce TN-C expression. The following hypotheses are proposed: (1) that PBK/ABK corneas present an ongoing "injury-response cycle" where the entire cornea stays in a continuous state of remodeling, (2) growth factors and/or cytokines play an important role in this cycle, and (3) the expression and deposition of TN-C affects the adhesive, migratory, proliferative and functional properties of corneal cells. Understanding these facets could lead to future therapeutic interventions. While TN-C, growth factors and cytokines are thought to play a significant role in PBK/ABK pathogenesis, other as yet unidentified abnormalities are probably also involved. Therefore, powerful new micro-sensitive techniques have been adapted for differential screening of genes from individual corneas. The hypothesis is that with these techniques, abnormalities in the expression of other genes important for PBK/ABK pathogenesis will be identified. There are three specific aims: (1) to determine the function of TN-C isoforms in PBK/ABK corneas by growing corneal cells on various isoforms of TN-C and determine rates of cell adhesion, migration, proliferation and function; (2) to determine the influence of growth factors and cytokines upon the expression of TN-C and TN-C binding integrins by: (a) identifying the abnormal growth factors/cytokines in PBK/ABK corneas, (b) determining the effects that these factors and dexamethasone have on the expression of
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TN-C and its binding integrins in corneal cells in vitro, and (c) determining if various isoforms of TN-C can affect the expression of TN-C binding integrins in vitro; and (3) to examine the differential gene expression in normal and PBK/ABK corneas and identify unique gene expression patterns by: (a) screening cellular mRNAs in normal vs. PBK/ABK corneas and cell layers using differential display, nucleic acid array and subtraction libraries; (b) determining if differentially-expressed genes are specific for PBK/ABK; and (c) determining whether altered gene expression in PBK/ABK is reflected at the protein level. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •
Project Title: EXTRA-RENAL REGULATION OF POTASSIUM HOMEOSTASIS Principal Investigator & Institution: Mcdonough, Alicia A.; Professor; Physiology and Biophysics; University of Southern California 2250 Alcazar Street, Csc-219 Los Angeles, Ca 90033 Timing: Fiscal Year 2002; Project Start 01-MAY-2001; Project End 31-MAR-2005 Summary: (Adapted from the Applicant's Abstract): Extracellular fluid (ECF) +} must be maintained within a narrow range. If ECF +] falls too low (hypokalemia), cell membranes hyperpolarize, and if ECF +] increases too much (hyperkalemia) cell membranes depobrize, both disrupt normal electrical excitability and can have life threatening cardiac effects. Kidneys and muscle work in concert to maintain ECF ]. During hypokalemia muscle ICF K is redistributed to buffer the fall in ECF }. During hyperkalemia K+ is pumped into muscle ICF until renal adjustments can occur. These important muscle specific homeostatic processes are only beginning to be understood at the molecular level. Evidence supports the hypothesis that K loss from muscle during hypokalemia results from decreased active K+ influx mediated by sodium pump (Na,KATPase, NKA) inhibition, and that K+ uptake during hyperktilemia is mediated by sodium pump activation. Our lab has established that during low K+ diet abundance of NKA subunits are depressed in an isoform and muscle specific manner: 60-95 percent fall in a2, not a 1. Using a novel K+ clamp technique, we recently showed that early in K+ restriction, prior to fall in a2, there is a severe blunting of both insulin stimulated K+ uptake, and of insulin stimulated redistribution of NKA ct2 type pumps from endosomes to the plasma membrane (PM). Evidence is mounting that the bumetanide sensitive Na,K,2C1 cotransporter also accounts for a component of muscle K+ influx and, thus, could play a role in potassium homeostasis. The overall aims are to determine the molecular mechanisms responsible for tapping muscle K+ stores during hypokalemia, for clearing excess plasma +] into the ICF store after K+ restoration, and to understand how these processes are altered in a set of clinically relevant paradigms. The contribution of both Na,K-ATPase isoforms and NKCCI in both red oxidative white glycolytic muscle will be studied with a compartmental analysis approach in which the following are assessed: whole body K+ uptake, muscle specific K+ transport, subcellular distribution and activity of K+ transporters, and pool size regulation of K transporter protein and mRNA levels. Aim 1 will test the hypothesis that the shift of K+ to ECF during K restriction is mediated by decreased plasma membrane (PM) expression of both NKA a2 and NKCC1 coupled to resistance to insulin stimulated K+ uptake, and that this process is altered in uremia accompanying chronic renal failure. Aim 2 will test the hypothesis that thyroid hormone or dexamethasone, both of which increase NKA cx2 (and perhaps NKCC 1), alter extrarenal control of K+ horneostasis. Aim 3 will test the hypothesis that the uptake of K+ from ECF to ICF during K+ restoration (following K+ restriction) is mediated by normalizing surface expression of both NKA a2 and NKCC1. Accomplishing these aims will identify the cellular mechanisms responsible for
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tapping and repleting the muscle K+ reservoir, which will, ideally, suggest strategies to manipulate muscle K stores in clinical settings. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •
Project Title: FACTORS IN THE PREVENTION OF TOXIC LIVER INJURY Principal Investigator & Institution: Boyer, Thomas D.; John Lee Professor of Medicine; Medicine; University of Arizona P O Box 3308 Tucson, Az 857223308 Timing: Fiscal Year 2002; Project Start 01-MAY-1990; Project End 31-MAR-2004 Summary: The glutathione S-transferases (GSTs) comprise a multi-class family of enzymes found in the cytosol of most cells. GSTs are enzymes of detoxification and protect cells from injury caused by a variety of endogenous and exogenous toxins and carcinogens. GSTs detoxify these reactive molecules by forming glutathione conjugates. The GSTs are dimeric proteins with independent catalytic sites, and it is unclear how the dimeric structure is necessary for function. The GST genes contain a number of regulatory elements that mediate increased expression in response to drugs. The physiologic factors that mediate expression of GSTs in the liver are undefined. Finally, different cells express different GST isozymes and the mechanisms that account for this cell specific expression are unknown. This proposal describes experiments that examine the affect of subunit interactions on catalysis. Techniques have been developed that allow the formation of heterodimers with mutations in only one of the two subunits. This approach is unique and allows for studies not previously possible. it was observed that the cytokine, interleukin 6, decreases the expression of a number of GST isozymes. The decrease in expression is mediated by elements in the promoter sequence of the GST gene and a unique nuclear protein has been identified that appears to mediate the decrease in transcription. This nuclear protein also is induced in the livers of animals during the acute phase response, and its appearance is associated with a decline in GST expression. In this proposal experiments are described that will further characterize the nuclear protein and define how it leads to a decrease in rates of transcription. Hepatic stellate cells (HSCs) upon activation become collagen-producing cells and account for the majority of collagen present in the cirrhotic liver. Normal HSCs express numerous GST isozymes, but upon activation most GSTs are lost and enzymatic activity against products of oxidant stress is reduced. Studies are proposed that will examine whether restoration of GST expression in activated HSC is associated with increased protection against oxidant injury and less collagen production in the GST expressing cells. It will also be determined whether the promoter region of the GST gene mediates the loss of expression of GST in activated HSCs. Finally, it has been observed that drugs such as phenobarbital induce GST expression in the liver both by increasing rates of transcription and mRNA stability. The latter appears to account for the greater expression of GSTs in pericentral vs periportal hepatocytes following treatment with phenobarbital. How phenobarbital selectively stabilizes mRNA in perivenous hepatocytes will be examined further. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen
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Project Title: DEPRESSION
GLUCOCORTICOID
RESISTANCE
IN
IMMUNE-BASED
Principal Investigator & Institution: Raison, Charles L.; Psychiatry and Behavioral Scis; Emory University 1784 North Decatur Road Atlanta, Ga 30322 Timing: Fiscal Year 2002; Project Start 01-JAN-2002; Project End 31-DEC-2006
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Summary: (provided by applicant): The training and research components of this Research Career Development Award application are designed to prepare the applicant for a career as an independent investigator in the area of mind-body interactions. The long-term objectives are to examine bi-directional relationships between the hypothalamic-pituitary-adrenal (HPA) axis and the immune system and determine the effect of these interactions on the regulation of mood and related neurovegetative functions in medically ill patients. The applicant will devote the 5-year K23 project period to combining his expertise in clinical diagnosis and treatment with rigorous training in neuroimmunology and neuroendocrinology, as well as in research methodology, data organization, biostatistics, and the ethical conduct of research. The training program will consist of an integrated curriculum of formal didactic course work and tutorials with the sponsor and other consultants. The applicant's immediate research goal during the award period will be to examine the relationship between immune system activation and glucocorticoid resistance in patients who develop depressive symptoms during treatment with interferon (IFN)-alpha for chronic hepatitis C virus (HCV) infection. The hypotheses to be tested are as follows: 1) Chronic treatment with IFN-alpha will induce resistance to the inhibitory effects of endogenous glucocorticoids leading to unrestrained release of corticotropin-releasing hormone (CR1I) and proinflammatory cytokines in the CNS, which in turn will lead to depressive symptoms and 2) Impaired glucocorticoid feedback inhibition at baseline (prior to IFNalpha treatment) will predict depressive symptoms as a result of relatively unrestrained immune system activation and release of CRH during IFN-alpha therapy. To test these hypotheses, the following specific aims are proposed: 1) To measure concentrations of the proinflammatory cytokines interleukin (IL)-l, IL-6 and tumor necrosis factor-alpha (TNF-alpha), and CRH in cerebrospinal fluid (CSF) of 100 patients with HCV, randomized to receive IFN-alpha treatment or to post-pone treatment until study completion, 2) To determine the correlation among CSF concentrations of proinflammatory cytokines and CRH and behavioral endpoints in these patients, and 3) To explore the effect of chronic IFN-alpha treatment on sensitivity to glucocorticoidmediated inhibition and to determine the relationship between glucocorticoid-mediated negative feedback and concentrations of IL-1, IL-6, TMF-alpha and CRH in CSF of IFNalpha-treated patients. All subjects will undergo in vivo and in vitro assessment of sensitivity to glucocorticoid inhibition of the HPA axis and immune system at baseline (prior to beginning IFN-alpha for subjects randomized to active treatment) and again one month later. At study week 12, subjects will receive a lumbar puncture to measure CSF concentrations of CRH, arginine vasopressin and proinflammatory cytokines. Results from this study will enable further understanding of the pathways by which mood disorders arise out of conditions of immune activation and will provide the foundation for the development of novel strategies to treat depression in the medically ill. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •
Project Title: GLUCOCORTICOIDS EFFECTS ON LEPTIN IN HUMAN OBESITY Principal Investigator & Institution: Laferrere, Blandine; St. Luke's-Roosevelt Inst for Hlth Scis Health Sciences New York, Ny 10019 Timing: Fiscal Year 2002; Project Start 15-MAY-1998; Project End 31-MAR-2004 Summary: This abstract is not available. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen
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Project Title: GLUCURONYL TRANSFERASE ACTIVITY IN THE FETAL PRIMATE Principal Investigator & Institution: Garland, Marianne; Assistant Professor; Pediatrics; Columbia University Health Sciences New York, Ny 10032 Timing: Fiscal Year 2002; Project Start 29-SEP-2000; Project End 31-AUG-2005 Summary: A broad pharmocipia of drugs are used in pregnancy. Despite this, our knowledge of the disposition of drug to the fetus and how the fetus metabolizes various drugs is limited. Glucuronyltransferase, a common phase II conjugation system, is down regulated in the fetus and undergoes induction near birth. Despite the limited activity of this enzyme in utero, we have shown that fetal glucuronidation of drugs can have significant effects on fetal concentration of both drugs and their metabolites in the fetus. Drug concentrations are diminished and metabolite concentrations can exceed those in the mother. Furthermore. premature induction of these enzymes could lead to more pronounced effects. To predict the likely effect a drug will have on the fetus, pharmacokinetic models are required to estimate fetal drug and metabolite concentrations. Using glucuronyltransferase as a model, the goal of this proposal, is to establish the role of fetal metabolism in overall maternal-fetal pharmacokinetics. Our overall hypothesis is that fetal metabolism accounts for a significant amount of the observed nonplacental clearance of drug from the fetus. In addition, measures of glucuronyltransferase expression during fetal life will predict the observable changes in fetal drug and metabolite concentrations. We propose to test these hypotheses by a series of experiments in the fetal baboon. A novel pharmacokinetic approach to the quantification of the rate of formation of glucuronide metabolites in the fetal baboon will be combined with biochemical assays of glucuronyltransferase activity and quantitative measures of expressed protein (protein immunoanalysis and steady-state mRNA) in fetal tissues. We will quantify the rate of glucuronide formation of buprenorphine, imipramine, acetominophen, and morphine in the fetal baboon across late gestation and correlate this with biochemical measures of enzyme-activity. We will quantify the change in metabolism following exposure to phenobarbital and dexamethasone, known inducers of glucuronyltransferase, and then quantify the effect this has on steady-state fetal-to-maternal ratios following maternal drug administration. In conjunction with recent advances in pharmacologic therapy for pregnant women, there is a pressing need for developing pharmacokinetic models which reliably define drug levels in the fetus. The long-term goal of this research is to reverse a trend which left the fetus as a therapeutic orphan. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen
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Project Title: HGF AND SIGNALING PATHWAYS IN HEPATIC TISSUE ASSEMBLY Principal Investigator & Institution: Michalopoulos, George K.; Professor and Chairman; Pathology; University of Pittsburgh at Pittsburgh 350 Thackeray Hall Pittsburgh, Pa 15260 Timing: Fiscal Year 2004; Project Start 01-APR-2004; Project End 31-MAR-2009 Summary: (provided by applicant): The purpose of this grant application is to explore new findings from our work as well as new models recently developed in our lab, in order to understand the mechanisms controlling assembly and formation of liver tissue. Gene array analysis of organoid cultures, composed of reassembled hepatic cellular elements, led to better understanding of the mechanisms by which dexamethasone, HGF and EGF regulate hepatic tissue assembly. We also found, unexpectedly, that in cultures maintained in the absence of dexamethasone HGF and EGF there is high
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proliferative activity, presumably driven by novel mitogen(s) not predicted from the literature derived from hepatocyte cultures or from whole animal, liver regeneration, models. The focused list of these potential mitogens identified from the gene array analysis will be studied in detail until the signaling molecules regulating this process are determined. After this is accomplished, the role of these mitogens in liver early embryogenesis, overall tissue repair and early carcinogenesis will be studied. We will also pursue further analysis of the role of HGF in liver embryology by utilizing an imported colony of Met -/+ mice, heterozygous for deletion of the HGF receptor (cMet). The livers of Met -/- embryos will be carried out alive further and beyond the day of embryonic lethality and will be studied as embryonic implants in the peritoneal cavity. We have recently developed this model and found out that it allows development and organization of all epithelial elements seen in mature liver including hepatocyte plates and bile ductules, even though mature portal triads do not appear. These studies will finally determine whether embryonic defects seen in livers of HGF -/- and Met -/- mice are primary to the genetic deletions or secondary to the placental anomalies seen in these embryos. The pathways leading to development of biliary ductules in wild type and Met -/- embryo livers after embryonic implantation will also allow determination of the importance of HGF as a key factor for biliary development, an item which has been often postulated but never proven. In addition to mitogenic signals, liver tissue assembly and repair also depends on the capacity of cellular elements to function as tissue restricted facultative stem cells for each other. Biliary cells can transdifferentiate to hepatocytes via the "oval cell" pathway. We have now shown that hepatocytes can transdifferentiate to biliary epithelium, in culture and in the whole animal. This relationship between hepatocytes and biliary epithelium establishes a new paradigm of organ stability in which mature, fully differentiated, cell types can function as "stem cells" for each other The signaling pathways and molecular determinants (growth and transcription factors) regulating this process will be studied in cultures, whole animals and embryonic implants. The above studies will provide insights and better understanding of the dynamics of liver tissue formation and provide paradigms with general applicability to other models of formation and maintenance of complex tissues. The comments in the CRITIQUE section were prepared by the reviewers assigned to this application and are provided without significant modification or editing by staff. The RESUME AND SUMMARY OF DISCUSSION section documents the final outcome of the evaluation by reviewers and is the basis for the assigned priority score Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •
Project Title: DEPENDENCE
HIPPOCAMPUS
/PITUITARY
RATIO
AND
ALCOHOL
Principal Investigator & Institution: Beresford, Thomas P.; Professor of Psychiatry; Psychiatry; University of Colorado Hlth Sciences Ctr P.O. Box 6508, Grants and Contracts Aurora, Co 800450508 Timing: Fiscal Year 2003; Project Start 05-APR-2003; Project End 31-MAR-2006 Summary: (provided by applicant): Possible disorders of the hypothalamic-pituitaryadrenal (HPA) endocrine axis have been implicated in both clinical and behavioral pathology resulting from the prolonged, heavy drinking of Alcohol Dependence. (AD) Studies report abnormally high levels of cortisol secretion during ethanol withdrawal as well as non-suppression of diurnal cortisol after dexamethasone in AD sufferers. Others found such neuro-endocrine abnormalities more frequently among Wernicke-Korsakoff Syndrome cases, suggesting a possible relation to brain injury. Studies from primates support this, observing chronically high levels of serum cortisol associated with
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degeneration of the hippocampal tissue. Noting previous research, we hypothesized that an increase in pituitary volume and a reduction in hippocampal volume would identify a sample of chronic, active, heavy drinkers. From volume measurements acquired by MRI scanning, we found that a decreased ratio of the hippocampus-topituitary volume (H:P ratio) characterized a group of recent, heavy drinkers as compared to a non-drinking control group. Although intriguing, this study was done in a convenience sample. We now propose to perform and extend this inquiry in a prospective fashion in order to establish whether a reduced H:P volume ratio serves as a state marker among AD subjects. If so, we ask a) does this indicate a reversible physiologic consequence of drinking or permanent structural change, and b) is reduced H:P ratio associated with hypercortisolemia, indicating loss of hippocampal feedback as a possible physiologic mechanism? To answer these questions, we will 1) measure baseline H:P volume ratios in 30, actively drinking, AD test subjects and in 30 matched, non-heavy drinking, non-AD control subjects, 2) measure H:P volume ratios serially in AD subjects after six months of ethanol abstinence, and 3) measure diurnal salivary cortisol secretion at baseline for both groups and serially for AD subjects. From this study we expect to develop valid, prospectively gathered, data that can begin to establish the clinical and patho-physiologic meaning of the decrease in the H:P volume ratio. We believe this line of investigation will ultimately shed new light on an important aspect of altered brain function due to sustained ethanol exposure as well as recovery of neuroendocrine functioning after cessation of heavy alcohol use. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •
Project Title: HORMONAL MODULATION OF TAXOL ACTION IN SOLID TUMORS Principal Investigator & Institution: Fan, Weimin; Professor; Pathology and Lab Medicine; Medical University of South Carolina 171 Ashley Ave Charleston, Sc 29425 Timing: Fiscal Year 2002; Project Start 01-APR-2002; Project End 31-MAR-2006 Summary: (PROVIDED BY APPLICANT): Taxol, a naturally occurring antimitotic agent, has shown significant cell-killing activity against tumor cells by induction of apoptosis. However, the mechanism of taxol mediated cell death and its relationship with taxol's well-known effects on microtubules and mitotic arrest is not entirely clear. Recent studies in this laboratory demonstrated that taxol's cell-killing activity (but not mitotic arrest) is selectively inhibited if tumor cells were pretreated with glucocorticoids, suggesting that taxol-induced apoptosis might occur via a signaling pathway independent of mitotic arrest. On the other hand, since glucocorticoids (such as dexamethasone) are routinely used in the clinical application of taxol to prevent hypersensitivity reactions and other adverse effects, this finding also raises a clinically relevant question as to whether the pretreatment with glucocorticoids might interfere with taxol's antitumor efficacy. The objectives of this proposal are to elucidate the mechanism by which glucocorticoids inhibit taxol-induced apoptosis and determine its potential influence on taxol's therapeutic effect. Meanwhile, utilizing the unique inhibitory effect of glucocorticoids on taxol's action, this proposed research also tries to determine the molecular basis of taxol-induced apoptosis via a "gene-directed" pathway. Therefore, this research application will pursue two major specific aims. Aim 1 is to evaluate the potential inhibition of glucocorticoids on taxol and docetaxel's therapeutic effects in vivo through establishment of appropriate animal models. This aim will confirm or negate the implication of glucocorticoid's effect on taxol or docetaxel's administration in vivo. Aim 2 is to investigate the molecular mechanism underlying taxol-induced apoptosis and glucocorticoid-mediated drug resistance. Based on the
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latest progress, this study will focus on elucidating the possible role of the NF-kB/IkBalpha signaling pathway in the regulation of apoptotic cell death induced by taxol and possibly other antimitotic agents in human solid tumor cells. The long-term goal of this research is to provide molecular insight into the mechanism and signal pathways that lead to taxol-induced cell death and glucocorticoid-mediated drug resistance. The information obtained from this proposed research may prove valuable for improving in the clinical application of this class of antineoplastic agents. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •
Project Title: HORMONAL DIFFERENTIATION
SIGNALING
AND
PREADIPOCYTE
Principal Investigator & Institution: Farmer, Stephen R.; Professor; Biochemistry; Boston University Medical Campus 715 Albany St, 560 Boston, Ma 02118 Timing: Fiscal Year 2002; Project Start 01-JAN-2001; Project End 31-DEC-2005 Summary: Obesity is one of the most common metabolic disorders and is a risk factor for several pathological conditions including type II diabetes, cardiovascular disease and hypertension. A major contributor to the obese state is a breakdown in the regulatory networks that control the balance between storage and utilization of triglycerides in adipose tissue. Adipocytes, the cells that perform this function, express a plethora of proteins that are involved in regulating glucose and lipid metabolism. Some of the proteins secreted from fat cells act at distant sites (i.e., skeletal muscle and brain) to integrate overall metabolism and regulate energy balance. Most notable among these substances are leptin and TNF-alpha. Leptin, the satiety factor, has been implicated in mechanisms that control fat utilization, while TNF-alpha appears to contribute to insulin resistance associated with obesity related type II diabetes. Expression of these proteins is induced during the differentiation of preadipocytes and is regulated by two main families of adipogenic transcription factors: C/EBPs and PPARs, from which C/EBPalpha and PPAR-gamma are considered to synergize with one another and regulate the terminal stages of adipogenesis, i.e., insulin-dependent glucose transport and leptin production. The sequential expression and activation of the adipogenic transcription factors is also regulated by extracellular effectors that stimulate a network of intracellular signaling pathways. The goal of this proposal is to determine the role of two of these pathways, PI3-kinase and p42/p44MAP kinase, in regulating adipogenesis. In Aim 1, we will define the role of these pathways in regulating the C/EBP-alpha and PPAR-gamma genes. Studies will involve blocking the transmission of signals through the PI3-K and p42/p44MAPK pathways using specific inhibitors of each, LY294002 and PD98059, respectively, and analyzing their effect on gene expression. In Aim 2, we will identify the role of specific mediators of these pathways by ectopic expression of constitutively active p42MAPK/Erk2 and Akt, dominant negative Akt, or MAPK phosphatase-1 in adipogenic cells. The ability of these enzymes to modulate the expression and activity of the C/EBPs and PPAR-gamma will be assessed by Northern and Western blots, EMSA/supershifts and other measures of transcriptional activity. In Aim 3, we will determine whether the C/EBPs and PPAR-gamma are direct targets of these signaling enzymes. This will involve modifying candidate sites of phosphorylation within these transcription factors using PCR-directed mutagenesis, followed by ectopic expression of the mutant proteins in adipogenic cells to determine how altering the phosphorylation state influences their function during adipogenesis. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen
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Project Title: HUMAN LIVER CYTOCHROMES P450 Principal Investigator & Institution: Raucy, Judy L.; Professor of Molecular Medicine; La Jolla Inst for Molecular Medicine Molecular Medicine San Diego, Ca 921213074 Timing: Fiscal Year 2002; Project Start 01-SEP-1994; Project End 31-JUL-2002 Summary: The marked inter-individual differences in drug oxidations observed in humans is often-times associated with particular subfamilies of P450 enzymes. Among the hepatic P450s to exhibit wide variations in substrate oxidations are those in the CYP2C subfamily. Factors contributing to this phenomenon include induction from exposure to certain xenobiotics. Investigations in our laboratory during the previous funding period noted that the antibiotic, rifampicin (RIF) induces proteins and mRNAs corresponding to CYP2C8, CYP2C9, and CYP2C19 in isolated human hepatocytes. These studies gave rise to the hypothesis that xenobiotic response elements (XRE) exist in the 5'-flanking regions of the CYP2C genes. Studies proposed in specific aim 1 are designed to isolate, clone, and sequence the 5'-upstream region of the human CYP2C19 gene. We hypothesize that isolation of this region will provide information regarding xenobiotics that affect expression of this P450. Moreover, isolation of this regulatory region of the CYP2C19 gene is a prerequisite for the experiments planned in specific aim 2. Experiments described in specific aim 2 will test the hypothesis that RIF enhances expression of the human CYP2C P450 genes. Mechanisms governing RIF- mediated induction of CYP2C8, CYP2C9, and CYP2C19 will be explored with our primary focus on distinguishing DNA elements within each CYP2C gene that are responsive to the chemical agent, RIF. In addition, investigation regarding CYP2C11 in rat hepatocytes have indicated that dexamethasone (DEX) enhances expression of this CYP2C enzyme which occurs via the glucocorticoid receptor (GR). Furthermore, RIF has recently been shown to activate the GR. These studies have directed us to hypothesize that the CYP2C enzymes in humans may also be induced by DEX through the GR. Interestingly, both CYP2C8 and CYP2C9 genes possess several GREs. Thus, we will examine whether DEX enhances human CYP2C expression and if glucocorticoid regulation is via the same response element as that identified for RIF. Finally, the function of the response elements will be tested in situ in specific aim 3. For these studies, cultured human hepatocytes will be treated with RIF and/or DEX and CYP2C mRNA and protein levels measured. In addition, catalytic activities representative of each CYP2C enzyme will be assessed to determine whether enhanced expression of the CYP2C genes ultimately leads to an increase in drug metabolism. In this manner, the function of the CYP2C enhancer elements can be verified in intact liver cells. Taken together, studies planned in this renewal application will extend previous investigation s on the human CYP2C enzymes and further examine causes for their inter-individual variability. Understanding molecular events associated with altered gene expression due to xenobiotic exposure can lead to appropriate mechanisms for identifying individuals with reduced or enhanced capacity to metabolize certain drugs. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen
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Project Title: HYPOTHALAMIC PITUITARY ADRENAL AXIS REGULATION BY IL 10 Principal Investigator & Institution: Hughes, Thomas K.; Associate Professor; Microbiology and Immunology; University of Texas Medical Br Galveston 301 University Blvd Galveston, Tx 77555 Timing: Fiscal Year 2002; Project Start 15-APR-2001; Project End 31-MAR-2006
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Summary: Interleukin-10 (IL-10) is a cytokine, which has a wide range of activities in the immune system. Neuroendocrine cells produce IL-10 and its receptor and expression is seen in the central nervous system as well, particularly during immune-related diseases. Little is known however, about IL-10's action in regulating hypothalamic-pituitaryadrenal (HPA) interactions. In vitro and in vivo evidence suggest that IL-10 is likely an endogenous regulator in the HPA axis. In vitro IL-10 acts like corticotropin releasing factor (CRF) to induce corticotropin (ACTH) production from pituitary cells. From hypothalamic cells, IL-10 induces the release of CRF. In vivo adrenal glucocorticosteroids (GCS) appear to be regulated by IL-10 normally and in response to stress. We hypothesize that IL-10 contributes to the homeostatic regulation of the HPA axis. This may occur through direct action on HPA axis tissues as well as indirectly through the inhibition of other cytokines or hormones. Our specific aims are as follows: 1) We will determine the differential expression and/ or regulation of IL-10 and its receptor in the HPA axis; 2) Linkage of regulation and the site of production with function will be determined by identifying the intracellular signal transduction pathways that IL-10 activates in cells of the HPA axis; 3) At the intercellular level, we will determine if IL-10 modulation of the HPA axis occurs through direct action on GCS availability and glucocorticoid receptor (GR); 4) At the whole animal level, we will determine the role of IL-10 in HPA responses during immune and physiologic stress. These studies will be accomplished in vitro using primary cells and tissue culture. In vivo studies will utilize normal and IL-10-deficient mice. Histological, molecular biological, and immunologically based techniques will be used. Results from this project should advance our understanding of how the HPA axis is regulated by IL-10 in particular and cytokines in general. These studies may lead to the identification of new molecules and mechanisms that mediate normal and pathological processes associated with stress and the HPA axis, such as Cushing's Disease, or other related diseases that have an immune component. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •
Project Title: IMMUNE SYSTEM INFLUENCES ON SENSORY REGENERATION Principal Investigator & Institution: Warchol, Mark E.; Reserach Associate Professor; University of Virginia Charlottesville Box 400195 Charlottesville, Va 22904 Timing: Fiscal Year 2002; Project Start 01-APR-2002; Project End 31-MAR-2003 Summary: This subproject proposes to investigate the potential role of macrophagederived cytokines in regulating cellular kinetics of neurosensory epithelia in the cochlea and vestibular system. The Specific Aims have not changed substantially in this second revision. A first goal is to determine which cytokines, from a group of seven, affect cell proliferation rates in isolated epithelial cultures from the avian utricle and cochlea using BrdU labeling techniques. A second aim will examine the potential role of resident macrophages in regulating cell turnover in explants of the avian saccule and utricle via the application of 3 pharmacological agents (L-phenylalanine methyl ester, dexamethasone, interleukin-10) that have been shown to selectively inhibit cytokine production by macrophages in other systems. Cell proliferation and apoptosis-mediated cell death will be assessed by BrdU labeling and application of the TUNEL assay, respectively. Aim 3 will explore the influence of resident macrophages on the proliferation of hair cells in the noise-damaged avian cochlea by examining the effects of administrating in vivo the immunosuppressive agents dexamethasone and cyclosporine-A. A final aim seeks to determine whether macrophages are present in the utriculus of normal mice and/or are recruited to sites of gentamycin-induced damage in mammalian utricular neurosensory epithelium. These experiments also will examine
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whether the regenerative capacity in isolated utricles is affected by the lack of CSF-1 and/or resident macrophages in the osteopetrotic (op/op) mutant mouse. Additional work in support of subprojects 1 and 3 will evaluate the potential role of macrophages in regulating the regeneration of gustatory and olfactory receptors again using the op/op mutant mouse model. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •
Project Title: INNER EAR IMMUNE RESPONSES Principal Investigator & Institution: Keithley, Elizabeth M.; Professor; Surgery; University of California San Diego 9500 Gilman Dr, Dept. 0934 La Jolla, Ca 920930934 Timing: Fiscal Year 2002; Project Start 01-JAN-2000; Project End 31-DEC-2004 Summary: (Adapted from the Investigator's Abstract) The abrupt loss of the sense of hearing is both frightening and alienating, but in some cases is reversible. The last ten years have seen the beginning of clinical treatment of hearing loss with systemic administration of immunosuppressive agents such as dexamethasone and prednisone. This course of treatment was tried because of the introduction of the idea that the inner ear is vulnerable to immune reactions and more importantly, that these immune reactions cause hearing losses. The fact that patients derive relief from their symptoms provides the motivation to both identify patients who may be helped by this treatment and to obtain the maximum understanding of immune mechanisms within the inner ear tissues. The development of an inner ear immune response involves the endolymphatic sac, an extension of the membraneous labyrinth within the temporal bone projecting into the dura adjacent to the sigmoid sinus of the posterior cranial fossa. The experimental, surgical destruction of the endolymphatic sac results in an attenuated immune response within the inner ear in response to an immunologic challenge. In normally housed laboratory animals and in the human endolymphatic sac reside the only immunocompetent cells found within the inner ear. Antigens introduced in the cochlear fluids very rapidly diffuse into the perisaccular connective tissue and subsequently are found within macrophages in the luminal space of the sac. For these reasons it is hypothesized that the endolymphatic sac is instrumental in connecting the inner ear to the systemic immune system and that signals generated here are used to initiate, modulate and resolve immune responses in the inner ear. The intent of the proposed experiments is to test this hypothesis and thereby gain an understanding of the initial events in the immune response. Such knowledge will enable clinicians to improve the treatments administered to patients who experience the unfortunate and potentially devastating trauma of rapidly progressing sensorineural hearing loss. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen
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Project Title: INTERPLAY OF MICROGLIA & ALLOREACTIVE CTL-DAMAGED GLIOMA Principal Investigator & Institution: Virasch, Nisha; Medicine; University of Colorado Hlth Sciences Ctr P.O. Box 6508, Grants and Contracts Aurora, Co 800450508 Timing: Fiscal Year 2003; Project Start 01-JAN-2003; Project End 31-DEC-2005 Summary: (provided by applicant): The prognosis for primary malignant brain tumors remains poor. In a Phase I trial, one specific type of effector cell, alloreactive cytotoxic T lymphocytes (CTL), have shown promise. Study of glioma cells, damaged by treatment with alloreactive CTL, with other auxillary brain cells such as microglia/macrophages in a reconstituted system may help us to better understand other complex interactions involved in situ. We hypothesize that after co-incubating glioma cells with alloreactive
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CTL, the resulting damaged (apoptotic/necrotic) gliomas will induce microglia/macrophage phagocytic function. We will also determine the effects of dexamethasone on the phagocytic function of microglia/macrophages. Lastly, we hypothesize that after co-incubating glioma cells with alloreactive CTL, the resulting damaged gliomas will induce microglia/macrophage activation. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •
Project Title: MAP KINASES IN NORMAL AND TRANSFORMED THYMOCYTES Principal Investigator & Institution: Sen, Jyoti; Dana-Farber Cancer Institute 44 Binney St Boston, Ma 02115 Timing: Fiscal Year 2002; Project Start 05-DEC-1997; Project End 30-NOV-2002 Summary: (Adapted from the Investigator's Abstract): Signals that result from thymocyte-stromal cell interactions and locally produced cytokines and hormones play a central role in the generation and maintenance of a competent immune system. These signals modulate very specific and highly regulated phases of proliferation and differentiation of thymocytes. Several nuclear factors, NF-kappaB, AP-1 and NF-AT, and p38 MAP kinase are induced in thymocytes by intrathymic signals. These signals regulate normal T cell development and are essential for Thymocyte survival. For example, glucocorticoids target immature thymocytes by down regulating intrathymically induced NF-kappaB and AP-1 in vivo. Ectopic induction of Ras in the thymus of mice expressing transgenic activated Ras also disregulates intrathymically activated signals and causes tumors. These observations suggest that appropriate intrathymic signals are needed for survival and differentiation of thymocytes and disruption of these signals by glucocorticoids or by activated Ras result in cell death or in tumorigenesis. Experiments described in this application are aimed at defining the role of the inducible nuclear factors and p38 MAP kinase activity in normal thymocyte survival and development. The specific aims are: i. to block p38 MAP kinase activity and assess the effect on T cell maturation; ii. to generate and analyze transgenic mice expressing dominant negative forms of upstream regulators of p38 MAP kinase to determine the role of this enzyme in the survival and/or development of T cells; and iii. to further define and clone a novel thymus specific "AP-1 binding" protein whose DNA binding activity is negatively regulated by dexamethasone treatment of thymocytes and by activated Ras in the thymus. Long term goals are to define that support survival of immature thymocytes and modulate T cell development. A clear knowledge of the nature of intrathymic signals will provide insight and molecular tools needed to understand T cell tumors of the thymus and to combat immunodeficiencies from genetic defects and from diseases such as AIDS. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen
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Project Title: PATHOGENS
MAST
CELL
TOLL-LIKE
RECEPTORS
AND
PARASITIC
Principal Investigator & Institution: Andrade, Marcus V.; Universidade Federal De Minas Gerais Rua Curitiba 832, 9 Andar, Minas Gerais Belo Horizonte, Timing: Fiscal Year 2004; Project Start 04-FEB-2004; Project End 31-JAN-2009 Summary: (provided by applicant) The project has three aims: 1) To determine whether or not glycolipids from Leishmania sp (L.sp.) and Trypanosoma cruzi (TC) activate mast cells (MC) through Toll-like receptors (TLR); 2) identify the TLR activated (most likely TLR2), the signaling pathways activated, and the biological responses of MC to these glycolipids; and 3) examine the role of MC in the immunological/pathological reactions
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to infection from the above organisms in a mouse model. A subsidiary theme is to evaluate the MC as a model for a) studies of the effect of drugs on TLR-mediated responses and b) for identifying other parasite components that act through TLRs. MC are an important component of the innate immune system and are now thought to be essential for elimination of parasite infestation but the mechanism is undefined. Recent reports indicate that MC express TLR2, 4, 6, and 8 which can be activated by bacterial glycolipids via TLR2 to induce production of inflammatory cytokines and degranulation: and via TLR4 to induce production of cytokines but not degranulation. Glycolipids from T.C. also activate TLR2 on macrophages but have yet to be tested on MC. The question we address is whether TLRs are the "recognition" receptors that allow MC to participate in parasite elimination through release of inflammatory mediators. The core signaling pathway activated via TLR2 and TLR4 has been identified but many questions remain, especially so for MC, on how TLR activation leads to gene expression for cytokine production and other biological responses. For aims 1 & 2, studies will be conducted with MC lines as well as cultured bone marrow-derived MC from TLR2- and TLR4- knockout mice. Purified glycolipid components from L.sp. and T.C. will be evaluated for potency along with bacterial glycolipids that activate specifically TLR2 or TLR4. Known TLR-signaling pathways will be examined along with pathways that are responsible for degranulation and cytokine production in antigen-stimulated MC. Dexamethasone will be used as a prototype drug to examine effects on TLR-mediated signals as this drug disrupts several key signaling events in antigen-stimulated MC. For aim 3, normal, mast cell-deficient and TLR-deficient mice will be used to evaluate host responses to L.sp. and T.C. infection using experimental models that are well established in our institution. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •
Project Title: MECHANISM OF ACTION OF CYTOKINES ON BRAIN AND PITUITARY Principal Investigator & Institution: Mccann, Samuel M.; Professor and Director; None; Lsu Pennington Biomedical Research Ctr 6400 Perkins Rd Baton Rouge, La 70808 Timing: Fiscal Year 2002; Project Start 01-APR-1995; Project End 31-MAR-2004 Summary: This abstract is not available. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen
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Project Title: MECHANISM OF STEROID ACTION IN LYMPHOID MALIGNANCY Principal Investigator & Institution: Distelhorst, Clark W.; Professor; Medicine; Case Western Reserve University 10900 Euclid Ave Cleveland, Oh 44106 Timing: Fiscal Year 2002; Project Start 01-NOV-1985; Project End 30-NOV-2004 Summary: This competing renewal application is for research into the mechanism of glucocorticosteroid induced apoptosis in lymphoma and leukemia cells. An in depth understanding of this mechanism at the molecular and cell biological level is essential to an understanding of how glucocorticoids work as therapeutic agents in lymphoid malignancies and how lymphoid malignancies become resistant to glucocorticoidinduced apoptosis. Using lymphoma and leukemia cell lines as a model system, this research focuses on two research themes that have arisen through work in this laboratory during the preceding funding period. One is focused on the role of proteasome-mediated c-Fos degradation in dexamethasone (DX)-induced apoptosis. This theme is based on the recent discovery that proteasome-mediated degradation of cFos is an early, Bc1-2-regulated step in DX induced apoptosis and that c-FosdeltaC, a c-
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Fos mutant that evades degradation by the proteasome, is a potent inhibitor of caspase activation and apoptosis. The other theme builds on evidence that calcium release from its intracellular reservoir in the endoplasmic reticulum (ER) is involved in mediating DX-induced apoptosis. Aim 1 will investigate the mechanism of c-Fos degradation in DX- induced apoptosis, focusing on the role of the glucocorticoid receptor and c-Fos - cJun interaction in this process. Aim 2 seeks to understand how c-Fos degradation contributes to apoptosis by investigating the mechanism by which the stable c- Fos mutant, c-FosdeltaC, inhibits apoptosis. This aim will investigate the effect of cFosdeltaC on glucocorticoid receptor activity and on AP-1-glucocorticoid receptor crosstalk. Also, this aim will identify genes regulated by c-FosdeltaC that function as apoptosis inhibitors. Aim 3 will investigate the role of ER calcium release in DX induced apoptosis, determining how ER calcium release triggers apoptosis and the relationship between ER calcium release and other events in apoptosis, including proteasomemediated c-Fos degradation and caspase activation. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •
Project Title: MECHANISMS OF TUMOR PROMOTION AND CARCINOGENESIS Principal Investigator & Institution: Honkanen, Richard E.; Biochem and Molecular Biology; University of South Alabama Mobile, Al 366880002 Timing: Fiscal Year 2002; Project Start 01-JAN-1994; Project End 31-JAN-2004 Summary: Determining the mechanisms that allow neoplastic cells to undergo uncontrolled proliferation is crucial to understanding carcinogenesis. Several recent studies indicate that protein phosphatases, like protein kinases, play important and specific roles in cell-cycle regulation; thus alterations in the expression or regulation of these proteins may affect cell-cycle progression and could even allow cells to undergo unregulated proliferation. A role for protein phosphatases in the tumor promotion process has also emerged from studies with okadaic acid, microcystin-LR, and calyculin A, three highly specific and potent inhibitors of certain serine/threonine protein phosphatases (PPases) that have tumor promoting activity. We have cloned and characterized three human PPases, and one, designated PP5, is particularly attractive for further studies. PP5 is potently inhibited by okadaic acid and calyculin A, two potent tumor promoters in mouse skin. However, unlike the other known PPases, which are expressed at constant levels, PP5 expression is high during log phase growth and low or undetectable in quiescent or differentiated cell cultures. The expression of PP5 is induced by the addition of serum and/or 17beta-estradiol in some cell types, and the inhibition of PP5 expression enhances the ability of both the p53 tumor suppressor protein and dexamethasone, a synthetic glucocorticoid agonist, to induce the expression of the p21 cyclin- dependent kinase inhibitor protein in A549 cells. Together these studies suggest that PP5 plays an important role in the regulation G1/S- phase transition. This proposal is designed to test the hypothesis that protein phosphatases play an important role in cell cycle progression; thus, the interference of their activity may contribute to the aberrant proliferative behavior of neoplastic cells. These studies will focus on the following specific aims: Aim 1. Further characterize the roles of PP5 in the normal and aberrant control of cell cycle progression. Aim 2.Characterize the relationship of PP5 in glucocorticoid mediated inhibition of cell growth and "cross talk" between signaling networks induced by hormones and growth factors. Aim 3.Characterize the mechanisms regulating the expression of PP5. Through these studies we hope to further characterize the role of protein phosphatases in the regulation of cell cycle and gain insight into the how protein phosphatases may be involved in the aberrant proliferation of neoplastic cells.
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Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •
Project Title: MENTORED DEVELOPMENT AW
PATIENT-ORIENTED
RESEARCH
CAREER
Principal Investigator & Institution: Liu, Zhenqi M.D.; Internal Medicine; University of Virginia Charlottesville Box 400195 Charlottesville, Va 22904 Timing: Fiscal Year 2002; Project Start 01-AUG-2000; Project End 31-JUL-2005 Summary: (Adapted from the applicant's abstract): Many disease states, including glucocorticoid excess and hyperthyroidism, are associated with accelerated protein catabolism, causing chronic muscle wasting and increasing morbidity and mortality. The exact cellular mechanisms responsible remain elusive. One of the possible mechanisms is glucocorticoid- or thyroid hormone-induced resistance to the anabolic agents in skeletal muscle. Insulin, branched chain amino acids (BCAA), balanced amino acid (AA) mixtures and insulin-like growth factor 1 (IGF-1) all have been demonstrated to retard proteolysis and/or enhance protein synthesis. The investigators propose to study the muscle's response to these four anabolic agents in the setting of acute and chronic glucocorticoid and thyroid hormone excess. The studies will be conducted in healthy human subjects with or without dexamethasone or triiodothyronine ingestion and patients with Cushing's syndrome or hyperthyroidism by examining: a) protein turnover in forearm muscle; b) the phosphorylation status of two key regulatory proteins involved in signaling mRNA translation (PHAS-I and p70 S6 kinase); and c) the activity, protein content and expression of several components in the ubiquitinproteasome proteolytic pathway. The results should help to define the mechanisms of accelerated proteolysis associated with glucocorticoid or thyroid hormone excess. They will define: l) whether insulin, BCAA, AA mixtures and IGF-1 increase protein synthesis by stimulating phosphorylation of two key regulatory proteins involved in the protein translation initiation (PHAS-I and p70 S6 kinase); 2) whether insulin, BCAA, AA mixtures and IGF-1 retard proteolysis via blocking the ubiquitin-proteasome proteolytic pathway; and 3) whether glucocorticoid or thyroid hormone excess activates the ubiquitin- proteasome pathway and antagonizes the anabolic actions of insulin, BCAA, AA mixtures and IGF-1. By understanding the cellular mechanisms underlying the accelerated muscle catabolism and the actions of four anabolic agents in muscle, it may be possible to correct the protein wasting and to decrease the associated morbidity and mortality. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •
Project Title: MENTORING CLINICAL INVESTIGATORS IN SCHIZOPHRENIA Principal Investigator & Institution: Malaspina, Dolores; Professor; Psychiatry; Columbia University Health Sciences New York, Ny 10032 Timing: Fiscal Year 2002; Project Start 18-AUG-2000; Project End 31-JUL-2005 Summary: This is an application for a Mid-Career Investigator in Patient-Oriented Research at Columbia University Department of Psychiatry. The candidate is an Associate Professor who completed residency training in 1987 followed by a Clinical Research Fellowship in 1989. Since then, she has had independent and continuous research support from both federal and private sources, which are expected to continue throughout the award period. The objective of Columbia University is to secure the candidate's time for mentoring beginning clinical investigators, including psychiatric residents, post-doctoral fellows, medical students, and nursing and for using her exceptional skills as a translator of science across disciplines and the clinical interface.
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Based upon this application, the candidate would become: training director for the Columbia NIMH Post-doctoral Schizophrenia Research Fellowship, coordinator of the PSY-1 psychiatric residency's research program, and the co-director of the Columbia Stanley Research Scholarship program for medical students. She would also provide research training for clinical psychology students and psychiatric nurses. The setting for her research and planned activities for this award is in the Columbia NIMH developing schizophrenia research center. The candidate's research proposals examine genetic and environmental etiologies of the schizophrenia syndrome, psychobiology of schizophrenia, and treatment response and determining prognostic variables of schizophrenia. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •
Project Title: MOLECULAR ANALYSIS OF THYMIC NEGATIVE SELECTION Principal Investigator & Institution: Clayton, Linda K.; Dana-Farber Cancer Institute 44 Binney St Boston, Ma 02115 Timing: Fiscal Year 2003; Project Start 01-APR-2003; Project End 31-MAR-2008 Summary: (provided by the applicant): The T-cell repertoire is generated through a tightly regulated developmental program of selection in which thymocytes bearing immunologically desirable T-cell receptor (TCR) specificities are preserved and those expressing harmful specificities are eliminated via an apoptotic mechanism termed negative selection Using representational difference analysis, we have cloned a novel inhibitor of NF-KB, IkBNS, which is rapidly expressed upon TCR-triggered but not dexamethasone- or gamma irradiation-stimulated thymocyte death The predicted protein contains 7 ankyrin repeats and is homologous to known IkB family members but lacks ubiquitination-based degradation signals In Class I and Class II MHC-restricted TCR transgenic mice, transcription of IkBNS is stimulated by peptides that trigger negative selection but not by those inducing positive selection (i.e., survival) or nonselecting peptides IkBNS blocks transcription from NF-kappaB reporters, alters NFkappaB electrophoretic mobility shifts and interacts with NF-KappaB proteins in thymic nuclear lysates following TCR stimulation. Using an anti-IkBNS mAb, the kinetics of IkappaBNS protein expression in the thymus have been determined and are very different flora those of IkappaBalpha. In addition, IkappaBNS localizes to the nucleus. Over-expression of IkappaBNS using retroviral transduction in fetal thymic organ culture alters the development of thymocytes and enhances anti-CD3epsilon-induced cell death. In this proposal, I describe plans to further characterize this thymic NFkappaB inhibitor. The effect of altered peptide ligands on IkappaBNS mRNA induction will be analyzed. The effects of IkappaBNS on negative selection in vivo will be analyzed in fetal thymic organ culture using mutant and wild type IkappaBNS, in transgenic mice expressing tissue specific IkBNS as well as in IkBNS gene deleted animals. I will also determine what proteins associate with IkBNS (NF-kB dimers or other proteins,). These studies will elucidate the role of IkBNS in the process of negative selection during thymic development. An understanding of the mechanism of negative selection may form the basis for manipulating the immune response allowing controlled elimination of autoreactive T cells and enhanced generation of T cells with medically relevant specificities. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen
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Project Title: MRI CONTRAST AGENT METHODS OF ASSESS TUMOR ANGIOGENESIS Principal Investigator & Institution: Schmainda, Kathleen M.; Assistant Professor; Radiology; Medical College of Wisconsin Po Box26509 Milwaukee, Wi 532264801 Timing: Fiscal Year 2003; Project Start 01-MAR-2000; Project End 31-MAR-2007 Summary: (provided by applicant): Patients with brain tumors are in desperate need of new therapies, such as those that inhibit new vessel formation (angiogenesis). Recent clinical testing of angiogenesis inhibitors has accentuated the need for non-invasive measures of tumor vasculature. Therefore, the long-term goal of this first-time competitive renewal application is to develop MRI contrast agent methods that efficiently evaluate the clinical potential of anti-angiogenic therapies. The general hypothesis is that MR contrast-agent methods will provide relevant markers of tumor angiogenesis if the biophysical relationships underlying these methods are well characterized. Excellent progress has been made in this regard, especially considering that the initial 5 year proposal was awarded 3 years of funding. Simulations and experiments, made in a rat brain tumor model, using contrast-agent T1 methods demonstrate that an accurate measurement of tissue blood volume fraction depends profoundly on the choice of imaging sequence and parameters. Studies to characterize the susceptibility-based blood volume measurements have shown that the susceptibility calibration factor is different for tumor and normal brain tissue, a new finding that may be due to the differences in vascular geometry. Treatment of the rat 9L gliosarcoma with the steroid dexamethasone demonstrated a vessel-size selective effect, which may parallel the balance of angiogenic factors. Using a novel GE(gradient-echo)/SE(spinecho) imaging method we demonstrated that dynamic susceptibility contrast (DSC) measures of total and microvascular rCBV (relative cerebral blood volume), along with vessel size information could be obtained from patients with brain tumors. Total rCBV and vessel diameter information ware found to be statistically different between low and high-grade tumors. Discerning this difference depends on the proper consideration of contrast agent extravasation effects. The specific aims are logical and exciting extensions of the initial aims. We will continue to develop and validate the susceptibility contrast methods for measuring blood volume and vessel diameter with i. the development of a novel tumor-specific simulation model and ii. MRI and histology measurements made in a rat 9L gliosarcoma model (Aim 1). The usefulness of these methods to track changes with therapy will be evaluated (Aim 2). Tumor-appropriate methods to measure cerebral blood flow (CBF) will be developed and validated (Aim 3). The optimized CBV, CBF methods will be applied to brain tumor patients and correlated with relevant immunohistochemical markers (Aim 4). Significance: Completion of these studies should move us closer to the ultimate goal of dramatically improving the diagnosis and management of patients with vascular tumors such as gliomas. Novelty: A key unique component of the proposed studies is the characterization of the biophysical relationships underlying the proposed methods. This will not only aid in assessing the accuracy of the techniques, but will also help us to exploit the wealth of information that can be derived from such measurements. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen
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Project Title: MUC1 AS THERAPEUTIC TARGET IN MULTIPLE MYELOMA Principal Investigator & Institution: Kufe, Donald W.; Professor; Dana-Farber Cancer Institute 44 Binney St Boston, Ma 02115 Timing: Fiscal Year 2003; Project Start 16-SEP-2003; Project End 30-JUN-2008
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Summary: The human DF3/MUC1 transmembrane protein is aberrantly expressed at high levels on the surface of multiple myeloma cells. Certain insights about the function of MUC1 have been derived from the finding that the cytoplasmic tail of MUC1 interacts with b-catenin, a signaling protein associated with the development of diverse human tumors. The interaction between MUC1 and b-catenin is regulated by receptor tyrosine kinases, members of the c-Src family and glycogen synthase kinase 3b (GSK3b). In multiple myeloma cells, stimulation with IL-7 induces interaction of MUC1 and the Lyn tyrosine kinase. Lyn phosphorylates the MUC1 cytoplasmic domain and increases binding of MUC1 to beta-catenin. The functional significance of this interaction is supported by the finding that MUC1 regulates nuclear targeting of beta-catenin. Our hypothesis is that MUC1 expression contributes to the malignant phenotype of multiple myeloma cells and that MUC1 represents a target for myeloma therapy. The novel isocoumarin 2-(8-hydroxy-6-methoxy-1-oxo-1H-2-benzopyran-3-yl) proprionic acid (NM-3) has recently entered Phase I trials as an orally bioavailable inhibitor of angiogenesis. In in vitro studies of multiple myeloma cells, NM-3 disrupts binding of MUC1 to b-catenin and, as a later event, downregulates MUC1 expression. NM-3 also induces killing of multiple myeloma cells at concentrations that have been achieved clinically without toxicity. The results further demonstrate that NM-3 potentiates the effects of standard agents, such as dexamethasone, in inducing multiple myeloma cell death. We propose to define the clinical activity of NM-3 in the treatment of multiple myeloma as a single agent and in combination with agents used in the treatment of this disease. Our hypothesis is that NM-3 will induce multiple myeloma cell death, at least in part, by disrupting MUC1 signaling. This hypothesis will be addressed by studying the effects of NM-3 on MUC1 function in multiple myeloma cells in vitro and on MUC1 expression in vivo. The Specific Aims are: 1) To define the functional significance of MUC1 expression in multiple myeloma cells; 2) To assess the role of MUC1 as a receptor in multiple myeloma cells; 3) To define the effects of NM-3 on MUC1 signaling and induction of lethality in multiple myeloma cells; and 4) To perform a Phase II pharmacokinetic/pharmacodynamic trials of NM-3 alone and in combination with standard agents for the treatment of multiple myeloma. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •
Project Title: NEPHRITOGENIC GLOMERULAR EPITHELIAL CELL ANTIGEN Principal Investigator & Institution: Chugh, Sumant S.; Medicine; Northwestern University Office of Sponsored Research Chicago, Il 60611 Timing: Fiscal Year 2002; Project Start 01-JUN-2001; Project End 31-MAY-2006 Summary: (adapted from the application) My goal is to be an outstanding basic scientist and clinician devoted to investigating the pathogenesis and treatment of immunologically mediated glomerular injury. My training from reputed medical institutions in India and the United States has allowed me to conduct several clinical studies that are now published in peer reviewed journals. My research effort over the past two years was focused on an animal model of complement-independent glomerular injury, and has formed the background for the current research proposal. The intellectually stimulating work environment at Boston Medical Center has opened a new horizon for me, and has inspired me to stay on beyond my nephrology fellowship to learn more about glomerular injury at a cellular and molecular level from leading authorities in the field. Under the guidance of my mentors, I plan to study changes in visceral glomerular epithelial cell (visceral GEC) morphology and permeability noted invivo in mice following injection of anti-aminopeptidase A (APA) antibodies, using cultured GECs (in-vitro) in the following manner: Specific Aim 1: We will first identify
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proteins that play a role in APA-mediated injury in cultured GECs by co-precipitating them with anti-APA antibodies. Antibodies to these putative proteins have applications in Specific Aims 2 and 3. Specific Aim 2: We will identify alterations in cell-matrix contact, cell-cell contact and cell polarity following sub-lethal injury with anti-APA. We will also study changes induced by antibodies against APA and its putative associated proteins in the distribution of APA and its associated proteins in vitro and in vivo. Specific Aim 3: We will study the impact on GEC monolayer permeability of appropriate factors from Specific Aims 1 and 2 and others that upregulate the expression of APA, followed by studies on the intracellular transport of APA during sub-lethal injury and recovery. Overall, our characterization of APA-mediated cell injury and its effects on GEC-permeability will help us understand the in-vivo observations mentioned above. This project allows me to learn new skills at three different labs that have access to state-of-the-art technology, and will facilitate my transition towards becoming an independent investigator. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •
Project Title: NEUROENDOCRINE ALTERATIONS IN FIBROMYALGIA AND IBS Principal Investigator & Institution: Chang, Lin; Medicine; University of California Los Angeles 10920 Wilshire Blvd., Suite 1200 Los Angeles, Ca 90024 Timing: Fiscal Year 2002; Project Start 13-SEP-1999; Project End 31-AUG-2004 Summary: The long-range goal of this proposal is to develop an understanding of the etiology of chronic functional pain syndromes, such as fibromyalgia (FM) and irritable bowel syndrome (IBS). The constellation of symptoms in the FM and IBS suggest a failure to appropriately activate pain modulatory mechanisms, a failure to activate neuroendocrine stress mechanisms, and an alteration in the autonomic response. Our general hypothesis is that a neurobiological model exists in patients with FM and IBS, which includes as its primary components alterations in the following CNS responses to stressors: inadequate antinociceptive response, blunted hypothalamic-pituitary-adrenal (HPA) axis response and altered autonomic balance and responsiveness. By applying similar methodologies across two functional pain syndromes (FM, IBS, and IBS plus FM), we will elucidate if altered CNS circuits are shared by these functional disorders or are site-specific and may explain the differences in symptom expression in the somatic or visceral domains. The first aim is compare the visceral and somatic pain thresholds before and after a noxious conditioning stimulus in three female patient populations (IBS, FM and IBS plus FM) with female controls, which would allow us to determine if altered perceptual responses are due to hypersensitive afferent pathways, or to a failure to activate antinociceptive systems. To further characterize alterations in the activation of specific antinociceptive pathways in response to conditioning stimuli, we will assess the effect of pharmacological manipulations of the opioid system (fentanyl, naloxone), and the noradrenergic system (corticotropin-releasing hormone (CRH), dexamethasone) on pain thresholds. Finally, we will compare brain activation in regions known to play central roles in antinociception in the 4 study populations with H215O PET brain imaging during visceral and somatic stimuli before and after the conditioning stimulus. In the second aim, we will test the responsiveness of the HPA axis, which has been shown to be altered in patients with FM, in the 4 study populations and address the potential mechanisms to explain these HPA axis alterations. To characterize these alterations, we will obtain serial measurements of plasma cortisol and ACTH over a 24hour period to assess baseline alterations in the diurnal pulsatile rhythm and synchrony of ACTH and cortisol. We will also assess HPA axis responsiveness to acute stress by comparing ACTH and cortisol levels before and after a visceral or somatic conditioning
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stimulus. Finally, in our third aim, we will compare autonomic responses to visceral and somatic stimuli during visceral and somatic conditioning paradigms. In order to determine if the response of central autonomic networks to visceral or somatic stimulation differ between the study groups, regional brain activation will be correlated to autonomic responses during the visceral and somatic stimuli in the PET studies using covariate analysis. The combination of experimental approaches should improve our understanding of the CNS mechanisms underlying functional pain syndromes. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •
Project Title: NEUROENDOCRINE EFFECTS OF OPIATES AND COCAINE Principal Investigator & Institution: Kreek, Mary J.; Professor and Head; Rockefeller University New York, Ny 100216399 Timing: Fiscal Year 2002; Project Start 01-AUG-2002; Project End 31-JUL-2007 Summary: (provided by applicant): Heroin, cocaine, and alcohol addictions, alone and in combination, along with their medical complications, including hepatitis B and C, AIDS, and psychiatric comorbidity, remain the major medical problems confronting our nation and much of the world. Effective treatments must be based on a fundamental understanding of the biological basis of each addictive disease, including the effects of exposure to drugs of abuse. This Project will continue to explore the atypical stress responsivity of the hypothalamic-pituitary-adrenal (HPA) axis seen in specific addictive diseases. Contributions of opioid and dopaminergic pathophysiological mechanisms will also be investigated. The specific hypotheses are: 1) that chronic cocaine addiction causes alterations in stress-responsive HPA axis function; 2) that alterations in HPA axis function caused by cocaine may be further modulated by alcohol abuse and/or opiate dependence; 3) that the relationship between cocaine addiction and alterations in HPA axis function is controlled in part by the endogenous opioid system; 4) that the regulation and release of corticotropin releasing factor (CRF) and proopiomelanocortin (POMC; and its peptide fragments including ACTH and beta-endorphin) are, in part, under the control of the endogenous opioid system and that changes in the sensitivity of the CRF-R1 receptor in the anterior pituitary are central to the atypical stress responsivity seen in different stages of addiction; 5) that psychological states which are believed to be both stress-related and important in the development and maintenance of addictions, may occur through alterations in HPA axis function and the endogenous opioid system; and 6) that the observed alterations in the physiology of the endogenous opioid system and its interactions with the stress-responsive HPA axis in addictive diseases may, in part, be influenced by specific single nucleotide and other polymorphisms in genes of the endogenous opioid system. The hypotheses will be explored using standard and novel paradigms of HPA disinhibition (by metyrapone and dexamethasone) and stimulation (by ACTH and CRF) testing alone and in combination. The role of the endogenous opioid system in affecting the HPA axis will be studied with opioid antagonists alone and in combination with HPA axis testing. This work, to be performed in patients with specific addictions and normal volunteers, will complement rodent and non-human primate studies conducted in our Center. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen
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Project Title: NOCICEPTIN INFLAMMATION/PAIN
&
ORL1
RECEPTOR
IN
SYNOVIAL
Principal Investigator & Institution: Palmer, Pamela A.; Anesthesia and Perioperative Care; University of California San Francisco 500 Parnassus Ave San Francisco, Ca 941222747
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Timing: Fiscal Year 2002; Project Start 27-SEP-1999; Project End 31-AUG-2004 Summary: Numerous studies on the function of the opioid receptor-like (ORL1) receptor and its endogenous peptide ligand, nociceptin, have been performed in the central nervous system (CNS), yet few studies have focused on their functions in the peripheral nervous system. Our preliminary data show that ORL1 receptors are expressed in peripheral sensory and sympathetic neuronal ganglia and that nociceptin plays an important role in synovial inflammatory and nociceptive processes via effects on peripheral sensory and sympathetic neuron terminals. We have recently shown that the regulation of prepronociceptin gene transcription is regulated by cAMP, glucocorticoids and estrogen. We propose to expand our preliminary studies to perform a comprehensive evaluation of the function of nociceptin and the ORL1 receptor in synovial inflammation and pain. The presence of prepronociceptin mRNA will be determined in peripheral neuronal ganglia and neuronal localization of ORL1 receptor and prepronociceptin mRNA will be identified using in situ hybridization techniques. Changes in neuronal expression of the ORL1 receptor and prepronociceptin mRNA and changes in ORL1 receptor protein and nociceptin peptide levels will be studied in rat models of chronic joint inflammation and nerve injury. The effect of steroid hormone treatment on mRNA and protein expression will be determined. Our preliminary studies demonstrate nociceptin's ability to enhance sympathetically mediated synovial inflammation. Mechanisms underlying this pro-inflammatory effect of nociceptin will be determined using plasma extravasation as a measure of inflammation. Furthermore, the ability of nociceptin to modulate other synovial inflammatory pathways will be studied. Lastly, nociceptin has been shown to produce differing responses on nociceptive pathways in the CNS. Specifically, nociceptin has hyperalgesic properties in brain, whereas intrathecal administration results in an anti-hyperalgesic effect at the spinal cord level. We hypothesize that nociceptin activation of the ORL1 receptor on sensory afferent terminals modulates peripheral nociceptive mechanisms. Our preliminary results indicate that infra-articular nociceptin enhances synovial nociceptive mechanisms as measured by capsaicin-induced dorsal horn c-Fos levels. The functional role of nociceptin in peripheral nociceptive mechanisms will be assessed by using a model of mechanical hyperalgesia in the rat knee joint. Recently, ORL1 receptor antagonists have been developed and these agents will be used to determine the significance of endogenous nociceptin in chronic synovial inflammation and hyperalgesia. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •
Project Title: NUTRIENT EFFECTS ON INSULIN ACTION Principal Investigator & Institution: Pagliassotti, Michael J.; Associate Professor; Medicine; University of Colorado Hlth Sciences Ctr P.O. Box 6508, Grants and Contracts Aurora, Co 800450508 Timing: Fiscal Year 2002; Project Start 01-MAR-1994; Project End 31-JUL-2004 Summary: This abstract is not available. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen
•
Project Title: OMEGA 3 LIPIDS AND CALORIES EFFECT ON SLE AND AGING Principal Investigator & Institution: Fernandes, Gabriel I.; Professor; Medicine; University of Texas Hlth Sci Ctr San Ant 7703 Floyd Curl Dr San Antonio, Tx 78229 Timing: Fiscal Year 2002; Project Start 15-APR-1998; Project End 31-MAR-2004
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Summary: The autoimmune prone NZBxNZW F1 (B/W) mouse is a useful model of systemic lupus erythematosus (SLE). Moderate calorie restriction (CR) delays the onset of disease and doubles the life span of these animals. Both CR and diets enriched in fish oil ((w-3) fatty acids decrease inflammatory cytokines, maintain (CD4+ CD44Low) T cell subsets and prevent the rise of memory (CD4+/CD44High) T cells with age. The involvement of Th-1 and Th-2 T cells subsets in the pathogenesis of murine (and probably human) lupus raises the question of whether CR and w-3 supplementation produce their effects by modulating anti- inflammatory cytokines. We propose that CR delays differentiation of CD44High T cells into Th-0, and/or Th-1 and Th-2 subsets by maintaining higher levels of adrenocorticosteroid (CORT) levels and apoptosis. In addition w-3 lipids and CR may also influence co-stimulatory molecules by increasing expression of antioxidant enzymes and reducing chronic oxidative stress. We propose that supplementation with w-3 fatty acids combined with CR maintains a youthful immune system by decreasing formation of free radicals and inflammatory cytokines and decreasing B cells autoantibody production. We hypothesize that CR delays formation of Th-1/Th-2 subsets by co-stimulatory interaction including lowering CD40 ligand expression and by normalizing apoptosis in both lymphoid cells and target tissues. Studies in specific aim 1 will determine if corn oil vs. fish oil lipids with and without CR affect the differentiation pathways and functional activity of Th-1 and Th-2 cells by modulating the interaction between CD28/CTLA-4 and B7-1/B7-2 costimulatory molecules in CD4+ T cells and B cells. Experiments in specific aim 2 will determine if prolongation of life span by w-3 fatty acids and/or CR is accompanied by increased anti-CD3 or dexamethasone induced apoptosis in thymic and splenic cells. Studies in specific aim 3 will determine whether prolongation of lifespan by w-3 fatty acids and/or CR is accompanied by decreased autoantibody production in B/W mice. In summary, our studies will examine whether w-3 fatty acids combined with moderate CR can further ameliorate autoimmune disease in B/W mice. These studies are especially important in view of the significant rise in the consumption of vegetable oils in recent years which may promote obesity and autoimmune disorders in the USA. In contrast, the anti-inflammatory w-3 fatty acids are consumed in negligible amounts. It is possible that moderate dietary changes will delay the onset of autoimmune diseases as well as significantly decrease the required doses of cytotoxic and immunosuppressive drugs normally used to treat SLE and other autoimmune diseases. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •
Project Title: RECEPTORS
OZONE
INHIBITION
OF
NEURONAL
M2
MUSCARINIC
Principal Investigator & Institution: Fryer, Allison D.; Professor; Environmental Health Sciences; Johns Hopkins University 3400 N Charles St Baltimore, Md 21218 Timing: Fiscal Year 2002; Project Start 01-MAY-1996; Project End 31-DEC-2004 Summary: (Adapted from the Applicant's Abstract): Exposure to ozone and to antigen causes airway hyperresponsiveness, which is due to increased release of acetylcholine from the vagus nerves. Increased release is due to dysfunction of neuronal M2 muscarinic receptors, which normally limit acetylcholine release, thus limiting bronchoconstriction. Loss of M2 receptor function and the subsequent hyperactivity is dependent upon eosinophils. Steroids are commonly used in the treatment of asthma on the assumption that they are anti-inflammatory. This proposal will address whether steroids prevent hyperreactivity by protecting neuronal M2 muscarinic receptor function. The effects of dexamethasone on hyperreactivity and M2 receptor function in vivo before and after exposure to ozone and antigen will be tested. The applicant will
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determine the specific mechanisms by which dexamethasone protects neuronal M2 receptor function; including whether dexamethasone inhibits eosinophil migration to nerves in the lungs by interfering with ICAM and VCAM expression. The applicant will also determine whether dexamethasone directly affects production of neuronal M2 receptors (measuring function, immunocytochemistry, M2 mRNA) in primary cultures of parasympathetic nerves. The applicant will also test whether steroids affect the activity of the human M2 receptor promoter (which the applicant has cloned). Finally the applicant will test whether dexamethasone also prevents hyperreactivity in a model that does not involve M2 receptor dysfunction (3 days post ozone). It is anticipated that these studies will lead to a greater understanding of the mechanisms by which hyperreactivity occurs, and the effects of steroids in countering hyperreactivity. Since the applicant has demonstrated that the neuronal M2 receptors are dysfunctional in man following exposure to ozone, and others have demonstrated M2 receptor dysfunction in asthmatic humans, these data may be applicable to the hyperreactivity characteristic of asthma and of exposure to pollutants in man. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •
Project Title: IMPLICATIONS
P
GLYCOPROTEIN
INDUCTION--KINETIC/DYNAMIC
Principal Investigator & Institution: Pollack, Gary M.; Professor and Chair; Drug Delivery & Disposition; University of North Carolina Chapel Hill Office of Sponsored Research Chapel Hill, Nc 27599 Timing: Fiscal Year 2002; Project Start 01-APR-2001; Project End 31-MAR-2005 Summary: (Applicant's abstract): Transport by P-glycoprotein (P-gp) is an important determinant of disposition for numerous pharmacological agents. A significant body of evidence has shown that decreases in P-gp activity can increase drug absorption from the GI tract, decrease drug/metabolite excretion in the liver and/or kidney, and enhance distribution of parent drug/active metabolites to target organs (e.g., the CNS) or pharmacologically relevant intracellular sites (e.g., leukocytes). Although the potential for induction of P-gp is well documented in the cancer chemotherapy literature, the implications of P-gp induction on the systemic disposition and pharmacological activity of P-gp substrates has yet to be addressed. Recent work in this laboratory has demonstrated that morphine is a substrate for P-gp-mediated transport, that alterations in P-gp activity influence morphine disposition and action and that morphine administration in vivo increases the P-gp content in rat brain. These observations are particularly important from a clinical perspective because of the key role of morphine in management of pain associated with cancer and other diseases requiring chronic analgesia. Therapeutic agents (e.g., anticancer drugs) that increase Pgp activity may decrease the efficacy of morphine in these patients. Conversely, induction of P-gp by morphine may limit the activity of other P-gp substrates. The long term objective of this research program is to explore the hypothesis that inducers of Pgp cause clinically relevant alterations in the disposition and action of P-gp substrates. The proposed project will utilize a multi-experimental approach to address the hypotheses that: 1) extent of P-gp induction in specific organs is a function of inducer potency and inducer concentration, 2) perturbations in the kinetics of a P-gp substrate can be predicted based on the degree of P-gp induction in organs/tissues, and 3) P-gp induction in humans can result in clinically significant alterations in the systemic disposition and action of P-gp substrates. In addressing these hypotheses, P-gp induction will be assessed in vitro in cultured hepatocytes (rat and human) and in vivo in selected organs, the impact of P-gp induction on drug disposition will be evaluated in
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isolated organ systems, and the implications of P-gp induction on systemic pharmacokinetics and pharmacodynamics will be examined in rats and humans. The potential importance of this research becomes apparent when one considers the number of therapeutic agents that are substrates of P-gp, the location of P-gp in organs of kinetic/dynamic importance, and the likelihood that numerous therapeutic, dietary, and environmental agents may modulate the activity of P-gp. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •
Project Title: PDGF ALVEOLIZATION
GENE
REGULATION
BY
VITAMINS
A
&
D
IN
Principal Investigator & Institution: Kaetzel, David M.; Pharmacology; University of Kentucky 109 Kinkead Hall Lexington, Ky 40506 Timing: Fiscal Year 2002; Project Start 29-SEP-2000; Project End 31-JUL-2004 Summary: The investigator proposes to assess the effect of RA, VitD, analogs, and dexamethasone individually or in combination on cell proliferation and expression of PDGFs and their receptors during lung development in vitro (Aim 1) and in vivo (Aim 2). This will include an evaluation of the effect of these treatments on alveolar formation and on lung function (Aim 2). Then, an analysis of the mechanisms regulating PDGF expression will be performed, aiming to characterize cis and trans elements potentially important on mediating transcriptional activation of the PDGF-A chain promoter during lung development (Aims 3 and 4). Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •
Project Title: PEDIATRIC ONCOLOGY GROUP Principal Investigator & Institution: Luchtman-Jones, Lori; Pediatrics; Washington University Lindell and Skinker Blvd St. Louis, Mo 63130 Timing: Fiscal Year 2002; Project Start 01-JAN-1978; Project End 31-DEC-2002 Summary: The Washington University Medical Center in St. Louis is one of the 39 full member institutions, 48 affiliate, 12 consortia and 9 CCOP institutions of the Pediatric Oncology Group who has pooled their patient resources and scientific expertise to study the natural history of childhood cancer, develop and compare effective therapeutic regimens and investigate the toxicity and effectiveness of new anticancer agents in the treatment of children with cancer. Additionally tumor specimens and occasionally normal tissue and blood samples are collected to determine more about the basic cancer biology and pathology of the disease. Group studies are ongoing in epidemiology, cancer control, pharmacology and pharmacokinetics. The investigators at the Washington University Medical Center include pediatric oncologists, radiologists, radiation oncologists, cytogenetists, neurologists, surgeons, and pathologists. All children with malignant disease are placed on cooperative group protocols if they are eligible and if informed consent is obtained. Data accessioned at the time the patient is placed on study protocol, during the study, and when off therapy is submitted to the Group Statistical Office for data analysis, interpretation and eventual publication. The investigators at Washington University Medical Center serve in multiple administrative and research capacities for the Group. The diagnostic studies, pathological findings, surgical procedure and therapeutic plan for all new patients and patients who relapse are discussed at the weekly Tumor Board Conference. The Principal Investigator has a phase I contract and works with 16 other POG institutions to establish the maximum tolerated dose of a new agent along with the pharmacology and, if indicated, the biologic response of the agent.
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Dexamethasone
Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •
Project Title: PRIMARY EPO SIGNALS FOR PROERYTHROID CELL EXPANSION Principal Investigator & Institution: Wojchowski, Don M.; Professor; Veterinary Science; Pennsylvania State University-Univ Park 201 Old Main University Park, Pa 16802 Timing: Fiscal Year 2002; Project Start 01-APR-1988; Project End 30-SEP-2003 Summary: Epo is expressed in response to hypoxia and upon binding to its transmembrane receptor on erythroid progenitor cells acts as an essential inhibitor of programmed cell death (PCD). Upstream effectors that dock at Epo-receptor complexes are relatively well defined (Jak2, Syp, HCP, STAT5, PLC-gamma, P13K, SHIP, Shc, Grb2, Crk-l, Cbl, Vav) and for many, links to mitogenic response pathways established. Yet, beyond the observations that EPO sustains Bcl-xl expression and protects against p53induced PCD in a cell cycle phase-independent fashion, little is understood about effectors of PCD. Studies aim to advance an understanding of mechanisms of this key response. Aim #1: In Epo, SCF-, IL-3 dependent FDCW2 cell lines expressing EpoR deletion and point- mutants, the extend to which Epo-dependent pathways to P13K/Akt kinase activation and Bad phosphorylation (versus hypothesized alternative pathways) inhibit PCD will be studied. hEGFR-EpoR chimeras with defined mutations in cytoplasmic domains have been expressed in erythroid progenitor cells in transgenic mice. Using this novel in vivo model (and thiamphenicol to induced splenic CFUe) essential signals for PCD inhibition also will be investigated. In purified CFUe Bcl2related, - associated factors whose expression is modulated by EPO also will be defined. Aim #2: Expression of Pim1 kinase is induced via minimal EpoR forms that efficiently inhibit PCD, and ectopically expressed Pim1 inhibits PCD. Based on these observations, mechanisms of Pim1-inhibited PCD will be investigated. Evidence for targets upstream of APAF1 will be sought; the ability of Pim1 to protect against PCD as induced by radiation, dexamethasone and/or Myc-induced PCD will be tested; and possible effects of Pim1 on the expression of Bcl2-associated, related factors will be studied. Also, ciselements and transfactors that regulate Pim1 gene expression in response to Epo versus SCF will be investigated in folate-deficiency and Diamond-Blackfan anemias, erythroid failure is characterized by PCD and EpoR mutations are associated with erythrocytosis and polycythemias. Insight into regulation of PCD gained from studies of Epo signaling should extend to related clinically important cytokine systems. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen
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Project Title: PROSPECTIVE PSYCHOPHYSIOLOGIC STUDY OF RISK FOR PTSD Principal Investigator & Institution: Orr, Scott P.; Associate Professor; Massachusetts General Hospital 55 Fruit St Boston, Ma 02114 Timing: Fiscal Year 2002; Project Start 17-AUG-2000; Project End 31-JUL-2005 Summary: There are no generally accepted methods for prospectively identifying individuals at risk for post-traumatic stress disorder (PTSD) after a traumatic event. However, several individual difference variables show promise as pre-trauma risk factors. Recent findings from the PI's differential conditioning study indicate that a conditioned skin conductance response is acquired more strongly and extinguishes more slowly in PTSD than in non-PTSD, trauma-exposed control subjects, i.e., that PTSD subjects are more "conditionable." Given that many PTSD symptoms may be conceptualized as conditioned responses (CRs), it is plausible that individuals who are more prone to acquire CRs in the first place would be more likely to develop this disorder. The proposed project will examine a promising set of pre-trauma
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psychophysiologic, endocrinologic, and psychometric measures for their ability to predict the occurrence and severity of PTSD following exposure to traumatic events in firefighter/EMT and police recruits. It is hypothesized that the selected pre-trauma measures will predict PTSD following an index traumatic event. Prior to receiving their recruitment training, subjects will undergo a battery of psychometric questionnaires. A Pavlovian differential conditioning procedure which pairs colored circles with a mildly aversive UCS will be administered. Other psychophysiologic tests found useful in measuring PTSD, e.g., startle response, and suppression of salivary cortisol by a low (0.5 mg) dose of dexamethasone, will also be measured. After the pre-trauma assessment, subjects will be closely followed for the occurrence of a traumatic event that meets the DSM-IV PTSD A.1 criterion. Three months after such an event, the trauma-exposed subject will return for psychodiagnostic, psychometric, and psychophysiologic assessment of PTSD. Logistic and multiple regression techniques will be used to examine the relationship between psychophysiologic, endocrinologic, and psychometric predictor measures and categorical and continuous PTSD outcome measures. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •
Project Title: PTSD IN CHILDREN WITH INJURIES: A LONGITUDINAL STUDY Principal Investigator & Institution: Saxe, Glenn N.; Assistant Professor; Boston Medical Center Gambro Bldg, 2Nd Fl, 660 Harrison Ave, Ste a Boston, Ma 02118 Timing: Fiscal Year 2003; Project Start 01-APR-2003; Project End 31-JAN-2008 Summary: (provided by applicant): The broad, long-term objectives of this proposed project are to develop and test an integrative model of biological and psychosocial variables influencing the course of post-traumatic symptoms in children who have experienced acute injuries. It is hoped that the funding permitted by this grant application will contribute to the understanding of risk factors for Post-traumatic Stress Disorder (PTSD) in children who have experienced injuries and to advance knowledge regarding the way in which biological and psychosocial variables interact to produce this debilitating disorder. This project aims to develop a comprehensive understanding of variables influencing the course of post-traumatic symptoms in injured children in order to eventually enable the early identification of children 'at risk' for post-traumatic stress disorder and to develop effective interventions. Methodological strengths of this project include: 1) the evaluation of injured children shortly after the traumatic event, 2) the sequential assessment of subjects over an 18-month time course, 3) the integration of biological and psychosocial assessment and data analysis, and 4) the use of innovative techniques for analyzing longitudinal data. A bio-behavioral conceptual framework is used in order to understand how psychobiological and psychosocial variables may influence each other to lead to the symptoms of PTSD. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen
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Project Title: REGULATION OF COLLAGENASE 3 GENE EXPRESSION BY CYTOKINES Principal Investigator & Institution: Rahman, Mahboob U.; Instructor of Medinice; Massachusetts General Hospital 55 Fruit St Boston, Ma 02114 Timing: Fiscal Year 2002; Project Start 14-APR-1998; Project End 31-DEC-2002 Summary: The overall goal of this proposal is to study the cytokine-mediated regulation of collagenase-3 gene expression in order to better understand the mechanisms involved in the degradation of articular cartilage in rheumatic diseases such as rheumatoid arthritis (RA) and osteoarthritis ( OA). OA is the most common form of joint disease and
46
Dexamethasone
is second only to cardiovascular disease as a cause of early retirement and disability. The destruction of hyaline articular cartilage is the hallmark of OA and disabling RA. Although various therapeutic regiment can cause symptom relief, no regiment has been proven to retard progression of articular cartilage degradation. In disease there is either a suppression of normal chondrocyte functions or in the constitutive inability of these cells to match the rate of repair with the increased rate of degradation of the matrix. Various cytokines and inflammatory mediators have been shown to either derange the synthetic functions of the chondrocytes of increase cartilage matrix catabolism by regulating various matrix-degrading enzymes, including the collagenases. Collagenase3 is specifically expressed in skeletal cells including chondrocytes and has been shown to have an additional cleavage site when compared to other collagenases. It has aggrecanase and gelatinase activity as well. It's expression is response to IL-1 and other inflammatory cytokines. Thus it may play a significant role in physiological skeletal remodeling and destruction of cartilage in disease. The collagenase-3 gene has been recently cloned, but the role of various cytokines in the transcriptional regulation of this gene is yet to be elucidated. We have cloned the collagenase-3 promoter from a human genomic DNA library. We will prepare reporter gene constructs (CAT) containing collagenase-3 promoter and transfect immortalized human cell lines and analyze the effects of selected cytokines/ligands e.g. IL- 1beta, TNF-alpha and TGF1-beta. The ciselements and trans-acting factors will also be characterized employing transfection and DNA-binding assays. We will also develop transgenic mice containing the collagenase promoter- beta-galactosidase fusion gene to analyze the expression and role of collagenase in development of arthritis in vivo. Transgenic mice will be treated with IL1ra, TNFR1-IgG1 fusion protein, and dexamethasone after induction of arthritis and the role of cytokines/ligands in the control of expression of collagenase and its role in development of arthritis will be elucidated. This proposal will provide insight into the mechanisms involved in the expression of collagenase-3 by cytokines and thereby may provide targets for developing novel therapeutic measures to inhibit cartilage destruction in joint disease. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •
Project Title: REGULATION OF NHE3 BY GLUCOCORTICOIDS, SGK1 AND NHERF2 Principal Investigator & Institution: Yun, Chang-Hyon C.; Medicine; Emory University 1784 North Decatur Road Atlanta, Ga 30322 Timing: Fiscal Year 2003; Project Start 01-JUN-2003; Project End 31-MAY-2008 Summary: (provided by applicant): The stimulative effect of glucocorticoids on the maintenance of fluid and electrolyte balance has been known for more than two decades. Pharmacological doses of methylprednisolone stimulated Na+ absorption in small animals. However, molecular mechanisms underlying this activation remain elusive. Na+/H+ exchanger NHE3 in the brush border membrane of intestine and kidney plays a major role in transepithelial Na+ absorption. We previously demonstrated that methylprednisolone in rabbits specifically stimulated NHE3 mRNA in ileum without affecting NHE1 mRNA levels. Others have shown that glucocorticoids specifically activated NHE3 mRNA in ileum, proximal colon and renal proximal tubules. These results suggest that glucocorticoids activate NHE3 activity by gene expression of NHE3. However, we recently found using Caco-2 cells that dexamethasone activates NHE3 transport without affecting NHE3 mRNA expression. This non-transcriptional activation of NHE3 by dexamethasone was demonstrated in OK cells, suggesting that transcriptional activation of NHE3 may not be the only
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47
determining factor in glucocorticoid-stimulation of NHE3. We found that dexamethasone enhanced NHE3 activity only in the presence of a NHE3 regulatory protein, NHERF2. We identified serum- and glucocorticoids-induced protein kinase 1, SGK1, as a protein interacting with PDZ domains of NHERF2. We demonstrated that SGK1 activated NHE3 activity and expression of "kinase-dead" SGK1 in OK cells markedly blocked the dexamethasone effect, demonstrating the importance of SGKI. We also showed that SGK1 directly phosphorylated NHE3 in vitro suggesting phosphorylation-dependent regulation of NHE3. In this application, we propose to investigate: (1) the roles of SGK1 and NHERF2 in activation of NHE3 by glucocorticoids; (2) molecular mechanisms underlying the activation of NHE3 by SGK1 and NHERF2 in response to glucocorticoid; and (3) the interaction between SGK1, NHERF2 and NHE3. This proposal will resolve complexity in NHE3 regulation by glucocorticoids, and enhance our understanding of protein-protein interaction in regulation of membrane transport proteins. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •
Project Title: REGULATION OF OUTFLOW FACILITY BY GENE TRANSFER Principal Investigator & Institution: Borras, Teresa; Professor; Ophthalmology; Duke University Durham, Nc 27706 Timing: Fiscal Year 2002; Project Start 01-AUG-1997; Project End 31-OCT-2002 Summary: (provided by applicant): The physiology of a given cell is determined by the coordinate expression of its genes. Our general, ongoing hypothesis is that manipulating the concentration of relevant proteins in the cells of the trabecular meshwork (TM) will allow us to modulate aqueous humor outflow facility in vivo. Most important, that introducing the nucleic acid sequences (sense or antisense orientation) coding for those proteins into the TM cells will help to elucidate their basic contribution to cellular function. Specifically, we hypothesize that a common pathway of the mechanisms by which cytoskeletal and stress related proteins (TIGR/MYOC) influence outflow facility might be mediated through the NF-kappaB signaling pathway effect on secretion. Similarly, we hypothesize that gene products abundant in our TM profile library but with a lower number of entries in their UniGene cluster (for all other tissues), might be indicative of additional important mechanisms influencing intraocular pressure (IOP). We also hypothesize that by combining the use of recombinant adenoviral (Ad) vectors with perfused human anterior segment organ cultures we will identify promoter sequences preferentially targeting distinct cells types of the intact human TM tissue. Finally, we hypothesize that the Brown Norway rats represent an ideal animal model to study TM gene transfer in vivo and that Cynomolgus monkeys will help to better elucidate the relevance of such gene transfer in glaucoma. To test these hypotheses we propose to transduce human TM (HTM) cells and perfused organ cultures with Ad carrying wild type, mutant and antisense forms of TIGR/MYOC cDNA and study the effects of their over-expression in stress protection, dexamethasone (DEX) interference, cellular secretion and modulation of NF-kappaB. To select 1-2 genes from our TM gene profile and study their impact on outflow facility. To construct Ad vectors with fused promoters (alphaB-crystallin, TIGR/MYOC, MGP and HC gp-39) to the LacZ gene and inject them into perfused human organ cultures. Finally, we propose to characterize different viral vectors (Ads and Adeno-associated viruses (AAV)) in Brown Norway rats and study the effect of our existing TM genes Ads in IOP. We will use the rat model to pre-select the vectors for use in cynomolgus monkeys. Even if some of these mechanisms and/or selected genes would turn out not to have primary relevance on the regulation of outflow, the investigation of their function in the TM and the optimization
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Dexamethasone
of their transfer will potentially provide important new insights concerning the involvement of gene expression in aqueous humor physiology. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •
Project Title: REGULATION OF SURFACTANT PROTEIN B GENE EXPRESSION Principal Investigator & Institution: Ballard, Philip L.; Professor; University of Pennsylvania 3451 Walnut Street Philadelphia, Pa 19104 Timing: Fiscal Year 2002; Project Start 10-DEC-2001; Project End 30-NOV-2006 Summary: Pulmonary surfactant protein B (SP-B) is a critical surfactant component for normal lung function, involved in formation of lamellar bodies in type II alveolar cells and both surfactant absorption and film stability. Developmental deficiency of SP-B contributes to surfactant deficiency in both human infants and knock-out mice is a newborn lethal condition. In addition, acquired deficiency of SP-B occurs in various animal models of acute lung injury and may contribute to human lung diseases involving inflammation. Thyroid transcription factor-1 (TTF-1) is a key transcription factor for activity of the SP-B promoter. In vitro studies during the past funding found that both phorbol ester and TGFbeta decrease SP-B gene transcription, that responsiveness to both agents maps to a region of the proximal SP-B promoter containing TTF-1 and HNF3 binding sites, and that there was a loss of both transcription factors from nuclei of treated cells. Recent preliminary data indicate that hormone induced differentiation of the surfactant system in human fetal lung epithelial cells is associated with increased TTF-1 gene expression. The overall goal of this renewal project is to further elucidate factors and mechanisms involved in both positive and negative regulation of SP-B gene expression is mediated, at least in part, through modulation of TTF- 1 expression or function. Most experiments will be carried out in a unique primary lung cell culture system in which differentiation of the surfactant system is induced and maintained by glucocorticoid plus cAMP treatment. Aim 1 will characterize hormonal induction of TTF-1 and its relationship to SP-B gene expression in cultured fetal lung epithelial cells examining dose and time course, transcription rate and TTF-1 isoforms. Aim 2 will examine the role of TTF-1 in SP-B gene expression using Aim 3 will address down regulation of SP-B by TGFbeta, investigating the role of Smad signaling, TTF-1 and phosphorylation. Aim 4 will examine the roles of TGFbeta and TTF-1 in SP-B expression in vivo using the mouse bleomycin lung injury model and two approaches to abrogation to TGFbeta signaling. The proposed studies are a logical extension of recent research and will provide new information related to this critical surfactant protein and transcription factor. This project involves interactions and collaborations with most of the other PPG projects and utilizes each core. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen
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Project Title: REGULATION OF SYMPATHETIC FUNCTION BY INFARCTION Principal Investigator & Institution: Habecker, Beth A.; Physiology and Pharmacology; Oregon Health & Science University Portland, or 972393098 Timing: Fiscal Year 2002; Project Start 01-AUG-2001; Project End 31-MAY-2005 Summary: Provided by applicant): The long term goal of the proposed research is to understand the molecular basis for the depletion of norepinephrine (NE) and loss of NE uptake in the peri-infarct sympathetic innervation following myocardial infarction (MI). Myocardial infarction can lead to ventricular arrhythmias and heart failure, and is a leading cause of mortality and morbidity in the United States. Changes in the cardiac innervation following Ml play a crucial role in the development of arrhythmias and
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49
heart failure, but the mechanisms that underlie the depletion of NE and loss of NE uptake in the peri-infarct innervation remain unknown. Several lines of evidence suggest a completely novel hypothesis that can account for these changes in the periinfarct innervation. First, infarction is accompanied by the elevation of inflammatory cytokines, and interleukin-6 (IL-6) in particular. Sympathetic neurons have receptors for IL-6, and other cytokines in the IL-6 family suppress NE synthesis and reuptake in sympathetic neurons while inducing the production of peptides including vasoactive intestinal peptide (VIP). IL-6 shares common receptors and signaling pathways with these related cytokines. and our preliminary data indicate that IL-6 suppresses NE uptake and induces VIP in cultured sympathetic neurons. Therefore, we hypothesize that IL-6 released in the heart after infarction causes the depletion of neuronal NE and loss of NE uptake observed in the peri-infarct cardiac innervation. To test this hypothesis we will determine if: 1) IL-6 suppresses NE and NE synthetic enzymes in sympathetic neurons, 2) IL-6 suppresses NE uptake and the NE transporter in sympathetic neurons, 3) IL-6 suppresses neunopeptide Y and induces other neuropeptides in sympathetic neurons, and 4) suppression of inflammatony cytokines or the absence of IL-6 during and after infarction prevents the depletion of NE and loss of NE uptake in the peri-infarct cardiac innervation. A variety of molecular, biochemical, and histological approaches will be used to carry out these experiments both in vitro and in vivo. These studies will determine if IL-6 is a key player in the pathological changes in the cardiac innervation following infarction, and will identify the sites at which IL-6 regulates sympathetic function. This work tests a novel hypothesis that would provide a mechanistic explanation for the depletion of neuronal NE and NE uptake following infarction, and will provide the scientific basis for the development of new therapies These studies will also provide new and important information about the expression of vasoactive peptides in the heart following infarction. Similar changes in IL-6 and NE uptake occur during heart failure as well, indicating that these studies will have implications beyond the treatment of myocardial infarction. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •
Project Title: RENAL AND HORMONAL MECHANISMS OF PERINATAL PROGRAMMING Principal Investigator & Institution: Woods, Lori L.; Medicine; Oregon Health & Science University Portland, or 972393098 Timing: Fiscal Year 2002; Project Start 27-SEP-2002; Project End 31-AUG-2006 Summary: (provided by applicant): Epidemiologic data have shown an inverse relationship between early growth patterns and increased risk for several adult diseases, including cardiovascular disease. This indicates that factors in the perinatal environment that affect fetal growth can "program" the individual for increased cardiovascular risk. Fetal exposure to excess maternal glucocorticoids may play an important role, in part by reduced activity of a placental enzyme (11beta-HSD) which is thought to protect the fetus from maternal steroids. However, the role of maternal glucocorticoids in perinatal programming, and the mechanisms by which they increase offspring blood pressure, are not known. These studies will test the overarching hypothesis that excess exposure to maternal glucocorticoids during development programs an individual for adult hypertension by suppressing the fetal intrarenal reninangiotensin system (RAS) and impairing renal development, thus causing permanent changes in renal structure and function. The Specific Aims are: 1) to determine the mechanisms by which exposure of the fetus to glucocorticoids from the mother programs the offspring for hypertension, and specifically, to test the hypothesis that
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excess maternal corticoids suppress the intrarenal renin-angiotensin system in the fetus/newborn, leading to a reduced number of nephrons, reduced renal function, and hypertension. The extent to which undernutrition caused by glucocorticoid administration plays a role in programming will also be examined. 2) To determine the critical period or "window" of sensitivity of offspring blood pressure to maternal glucocorticoids and whether it coincides with nephrogenesis. Corticosterone (a naturally-occurring glucocorticoid), dexamethasone (a synthetic glucocorticoid not inactivated by 11beta-HSD), or carbenoxolone (an inhibitor of 11beta-HSD) will be given to pregnant rats either throughout gestation or for only the first half (pre-nephrogenesis) or second half (during nephrogenesis) of pregnancy. Careful attention will be given to choice of doses of these agents, as well as to use of pair-fed controls. Intrarenal RAS activity will be measured in fetal and newborn animals. Arterial pressure, renal function, and nephron number will be measured in chronically instrumented juvenile and adult offspring. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •
Project Title: ROLE OF UROCORTIN IN MAMMALIAN BRAIN AND PITUITARY Principal Investigator & Institution: Seasholtz, Audrey F.; Associate Professor; Biological Chemistry; University of Michigan at Ann Arbor 3003 South State, Room 1040 Ann Arbor, Mi 481091274 Timing: Fiscal Year 2002; Project Start 15-FEB-2001; Project End 31-JAN-2005 Summary: (Adapted from the applicant's abstract) Corticotropin-releasing hormone (CRH) is recognized as the key hypothalamic regulator of the mammalian stress response. Within the hypothalamic-pituitary-adrenal axis (HPA), hypothalamic CRH is the principal hormone controlling pituitary ACTH secretion. At other sites in the central nervous system, CRH is thought to act as a neurotransmitter to mediate stress-related behavioral, autonomic, and immunological responses. The effects of CRH are mediated by two classes of CRH receptors and are modulated by a CRH-binding protein. Several years ago, a new mammalian CRH-like ligand was identified by Vaughan and colleagues. This 40 amino acid neuropeptide, called urocortin, is 43 percent identical to CRH and binds to both of its receptors, albeit with a higher affinity to CRHR2. Because CRH and urocortin can bind to and activate both CRH receptors, iv or icv administration of urocortin results in very similar physiological responses to those observed with CRH. Since urocortin is colocalized with CRH receptors in a number of sites, the investigator hypothesize that urocortin mediates or modulates some of the physiological effects previously thought to be mediated by CRH. The proposed work will specifically examine the in vivo role of urocortin in the CNS and pituitary. Based upon physiological experiments and neuroanatomical data, the investigator hypothesizes that urocortin acts in the brain to modulate feeding and drinking behavior, anxiogenic behavior, and autonomic function. Also it appears that urocortin might act in a paracrine fashion in the anterior pituitary to modulate basal or CRH-mediated ACTH secretion. To test these hypotheses, the investigator will further characterize the expression of urocortin mRNA in the adult mouse CNS and pituitary under basal and altered physiological states (stress, altered glucocorticoid status, food or water deprivation) using in situ hybridization and RNAase protection assays. Second, she will create an inducible brain-specific urocortin knockout mouse and characterize the physiological and behavioral changes resulting from the lack of urocortin expression in the CNS. Third, primary anterior pituitary cultures will be used to test the role of pituitary urocortin in basal and stimulated ACTH secretion from corticotropes. Finally, the investigator will examine the molecular mechanisms responsible for regulation of
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urocortin expression in cultured cells and in transfection assays. These studies will allow a more accurate determination of the physiological role(s) of urocortin in CNS and pituitary, and to differentiate its roles from those of CRH. As dysregulation of CRH activity is thought to be important in major depression, anxiety disorders, and anorexia, a clearer understanding of the role(s) of urocortin in CNS and pituitary sites may be important to our understanding of the pathophysiology of these human disease states. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •
Project Title: SIGNAL TRANSDUCTION TO P70 S6 KINASE 1 Principal Investigator & Institution: Blenis, John; Professor; Cell Biology; Harvard University (Medical School) Medical School Campus Boston, Ma 02115 Timing: Fiscal Year 2002; Project Start 01-SEP-1995; Project End 31-MAR-2004 Summary: Description(adapted from the applicant's abstract): Inappropriate regulation of a variety of signal transduction processes can result in a multitude of diseases due to improper differentiation and development or malignant transformation. PI3K plays a critical role in cell proliferation. Until recently, however, little was known regarding how PI3K signaled. P70S6K1 was the first signaling protein kinase shown to act downstream of PI3K. Since then, S6K1 activation has been shown to require several lipid-dependent kinases, binding to activated rho family G proteins (Cdc42/rac1), and phosphorylation at multiple sites by distinct inputs. Underscoring its importance, oncogene products such as Dbl, TIAM-1, and Akt specifically activate S6K1, and the T cell immunosuppressants rapamycin and dexamethasone specifically antagonize its activation. The two isoforms of S6K1, alpha-1 and alpha-2, are believed to regulate gene expression and protein translation, respectively. However, little is known of their downstream targets. The research proposed in this application addresses issues regarding the regulation of S6K1 activation, downstream signaling and its role in cell proliferation. The first objective is to define the mechanisms of S6K1 activation by determining how phosphorylation of the autoinhibitory domain and two critical sites in the linker region, S371 and T389, are regulated, and the consequences of these phosphorylations to S6K1 activation. In addition, how these events are coordinated with and cooperate with the phosphorylation of T229 in the activation loop by PDK1 will be examined. The second objective is to identify, using molecular and biochemical approaches, S6K1 associated proteins and assess their roles in regulation of S6K1 or signaling by S6K1. These proteins are expected to be either upstream regulators, downstream targets, or scaffolding proteins that assemble the S6K1 signaling complex. The third objective is to characterize the biological function of S6K1 in a cell system that will allow elucidation of the linkage between S6K1 and the cell cycle machinery. The fourth objective is to characterize transgenic mice expressing S6K1 in a transgenic T-cell model, to assess the role of the protein kinase in murine T-cell proliferation, differentiation, and ultimately function. Since several hematopoietic oncogenes and T cell immunosuppressants modulate S6K1 activity this will allow the examination of the functions of S6K. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen
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Project Title: S-NITROSOTHIOL BREAKDOWN BY AIRWAY EPITHELIAL CELLS Principal Investigator & Institution: Gaston, Benjamin M.; Associate Professor of Pediatrics; Pediatrics; University of Virginia Charlottesville Box 400195 Charlottesville, Va 22904 Timing: Fiscal Year 2002; Project Start 01-JAN-1999; Project End 31-DEC-2002
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Summary: S-Nitrosothiols (SNOs) in general - and S-nitrosoglutathione (GSNO) in particular - are stable, potent bronchodilators which also have immune regulatory functions and are present in the normal human airway. Asthmatic bronchospasm is associated with paradoxically low airway SNO levels - and undetectable GSNO levels despite relatively high concentrations of nitric oxide ( NO) in expired air and upregulation of inducible-nitric oxide synthase. This paradox may be best explained by considering GSNO to be a reservoir of bioactive nitrogen oxides in the airway - as it is in brain and other tissues - the breakdown of which is accelerated in asthma. In this sense, airway SNO catabolism may contribute both to high expired NO concentrations and to bronchospasm in asthmatic patients. This project will test the hypotheses that 1) airway epithelial cells catabolize SNO; 2) the SNO catabolic activity of airway epithelial cells is altered by stimulants relevant to asthma pathophysiology; and 3) airway epithelial cellmediated SNO catabolism inhibits airway smooth muscle relaxation. A new methodology will be used to study the conversion of SNO to NO in the presence of airway cells. Preliminary data using this system suggest that there are epithelial cell proteins which catalyze GSNO breakdown. These proteins will be characterized with regard to size, sequence, reactant and product stoichiometry and kinetics. Further, the effects of interleukin 4, vasoactive intestinal peptide, dexamethasone, acivicin, aurothioglucose and hemoglobin on epithelial GSNO catabolism and nitrogen oxide transport will be investigated. Finally, the relevance of epithelial GSNO breakdown will be studied in a bioassay of guinea-pig airway smooth muscle relaxation. In summary, this project will test the overall hypothesis that GSNO-mediated relaxation of airway smooth muscle is inhibited in the presence of airway epithelial cells by a regulated protein which catalyzes GSNO catabolism. If this hypothesis is proven, prevention of GSNO catabolism may define new asthma therapies. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •
Project Title: ST.LOUIS-CAPE GIRARDEAU CCOP Principal Investigator & Institution: Henry, Patrick H.; Chairman; St.Louis-Cape Girardeau Ccop 12800 Corporate Hill Dr St. Louis, Mo 63131 Timing: Fiscal Year 2002; Project Start 01-JUN-1987; Project End 31-MAY-2007 Summary: (provided by applicant): The St. Louis-Cape Girardeau CCOP is a consortium of four hospitals in two separate bi-state health service areas serving parts of eastern Missouri and western Illinois. The Investigators from the St. Louis Metropolitan area are affiliated with one or both of the two hospitals in the consortium and have worked together for the past eighteen years in cancer treatment research protocols and more recently, in cancer control research studies. The Cape Girardeau Investigators have worked with CCOP for the past nine years and are affiliated with two hospitals in that city. During the next five years we expect to accrue at least sixty credits per year for cancer treatment research protocols of the NSABP and SWOG and at least seventy five credits (new participants and follow-up) per year for cancer control and prevention studies. These cancer control credits will be derived primarily from our participation in the Breast Cancer Prevention Trial-1, Prostate Cancer Prevention Trial-1 and the Breast Cancer Prevention Trial-2. We will continue to provide high quality data to the Southwest Oncology Group and the National Surgical Adjuvant Breast and Bowel Project which are our research bases, utilizing the data management system developed during the past eighteen years. In summary, we will continue our excellent performance of the past eighteen years in cancer treatment research studies and extend our more recent participation in cancer control and prevention trials. The past experience and
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capabilities of the Investigators and Clinical Research Associates provides a strong base for continuing development of this Community Clinical Oncology Program. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •
Project Title: STRESS, DIURNAL CORTISOL AND BREAST CANCER SURVIVAL Principal Investigator & Institution: Spiegel, David; Professor; Stanford University Stanford, Ca 94305 Timing: Fiscal Year 2002; Project Start 01-SEP-2002; Project End 31-AUG-2003 Summary: Breast cancer can be understood as a series of stressors, including physical symptoms, treatment side effects, fears about disease progression, and disruption of social and vocational roles. Stress can be further exacerbated by social isolation and maladaptive coping, which may in turn adversely affect the endocrine system, and potentially the rate of disease progression. Conversely, enhanced psychosocial support via group therapy or other means may improve medical outcome by buffering the consequence of such stress and thereby ameliorating endocrine function. Previous research in this laboratory with metastatic breast cancer patients has demonstrated an association between diurnal cortisol rhythms and survival, revealing flatter slopes (i.e, loss of normal diurnal variation to be associated with shorter survival. This is of particular importance because glucocorticoids have been shown to facilitate tumor growth. This program of research is designed to examine the relationships among stress, dysfunction of the hypothalamic-pituitary-adrenal axis [HPA], and breast cancer progression. A sample of 100 women with hypothalamic- pituitary-adrenal axis [HPA], and breast cancer progression. A sample of 100 women with metastatic breast cancer will be recruited for intensive evaluation of their stress response. Salivary cortisol samples will be taken to determine the pattern of diurnal variation in cortisol and to examine its relationship to stress and survival time. Regulation of the stress response system will be studied utilizing low-dose activation of cortisol will be evaluated using the Trier Social Stress Task. This systematic assessment of stimulation and suppression of the cortisol stress response and its relationship to breast cancer progression will thoroughly examine the hypothesis that endocrine dysfunction may mediated the relationship between stress and breast cancer progression. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen
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Project Title: SYSTEMS
STRESSOR
CONTROLLABILITY
AND
NEUROENDOCRINE
Principal Investigator & Institution: Helmreich, Dana L.; Biology; Middlebury College Old Chapel Bldg Middlebury, Vt 05753 Timing: Fiscal Year 2003; Project Start 01-FEB-2003; Project End 31-JAN-2005 Summary: (provided by applicant): The experiments in this grant application propose to use animal models to describe the regulation of neuroendocrine systems during stress. It is hoped that the results of these studies will begin to elucidate why these systems become dysregulated in human depression. Changes in both the hypothalamicpituitaryadrenal axis (HPA) and the hypothalamic-pituitary-thyroid axis (HPT) have been documented in depressed patients. The activity and regulation of these neuroendocrine systems will be characterized in adult male rats using a paradigm that has been considered an animal model of depression. The paradigm is the controllable/non-controllable (C/NC) stress paradigm. In this paradigm one animal, the executive animal, can terminate his stress (a mild-electric foot shock), but his yoked partner cannot. Both stress groups receive an identical physical stressor, but differ in the
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psychological aspect of coping. The yoked animals exhibit escape from the suppressive effects of dexamethasone (DEX) on the HPA axis, as do depressed patients. Furthermore, recent work from our lab has also demonstrated that yoked animals, but not executive, have decreased levels of thyroid hormone levels; decreased in thyroid hormone levels have also been linked to human depression. In the proposed experiments, neuropeptide mRNA and hnRNA levels will be measured in the hypothalamus to characterize central drive to both the HPA and HPT axis during and after C/NC stress. These neuropeptide mRNA and hnRNA levels will also be determined in executive and yoked animals pre-treated with DEX. The ability of DEX to penetrate the brain and activate glucocorticoid receptors will also be determined in executive and yoked animals. The results of these studies will fully characterize activity of both the HPA and HPT axis in executive and yoked animals, and also help elucidate the mechanisms underlying escape from DEX suppression. The effects of repeated exposure to either C/NC stress will also be determined. Changes in basal and stressinduced changes in hormone levels will be measured after 7 or 14 days of stress. Changes in neuropeptide mRNA levels will also be determined, along with measurement of Mrna encoding both glucocorticoid, mineralocorticoid, and thyroid hormone receptors. The results of these studies should provide information regarding vital neuroendocrine sytems that often become dysregulated in human depression. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •
Project Title: STRUCTURAL ANALYSIS OF THE ALPHA 2 ADRENERGIC RECEPTOR Principal Investigator & Institution: Lanier, Stephen M.; Professor and Chair; Pharmacology; Louisiana State Univ Hsc New Orleans New Orleans, La 70112 Timing: Fiscal Year 2002; Project Start 01-JUL-1987; Project End 30-NOV-2002 Summary: (Applicant's Abstract) A long term objective of this research effort is to define factors that influence the specificity and efficiency of signal propagation by receptors (R) coupled to heterotrimeric G-proteins (G). A major determinant of signalling specificity/efficiency for G-protein coupled receptors is the cell specific expression of the subtypes of the primary signalling entities, R, G and effector (E). Another major site for regulating signalling specificity/efficiency lies at the R-G or G-E interface where these interactions are influenced by cell architecture, stoichiometry and accessory proteins that regulate signal transfer from R to G or G to E. This application focuses on the identification and characterization of a candidate "accessory protein(s)" that is a novel and powerful activator of G-proteins. The applicants have recently achieved partial purification of the protein, termed the G-protein activator, from the neuroblastoma-glioma cell hybrid NG108-15. The immediate goals of this application are to functionally characterize and determine the primary sequence of the G-protein activator. The SPECIFIC AIMS are: 1) Characterize the interaction of the G-protein activator with G-proteins; 2) Functional characterization of the G-protein activator relative to signal transduction events; 3) Determine the primary sequence of the Gprotein activator. The G-protein activator and related molecules may regulated the activation of G-proteins independent of receptors or perhaps regulated receptor signalling via their ability to influence signal intensity and/or duration of specific transduction pathways. Molecules of this class may regulate the signal amplification commonly observed with signalling events involving G-proteins and may be of particular significance in tissues requiring rapid signal processing or under conditions of aberrant cell growth and development. The demonstration of proteins that influence signal propagation downstream from receptor at the level of G-protein presents a new
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frontier for understanding disease processes and developing novel therapeutics that either mimic or interfere with their actions. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •
Project Title: STUDY OF DEXAMETHASONE IN NEONATAL LUPUS CHB Principal Investigator & Institution: Buyon, Jill P.; Professor; Hospital for Joint Diseases Ortho Inst Orthopaedic Institute New York, Ny 10003 Timing: Fiscal Year 2002; Project Start 30-SEP-2000; Project End 31-AUG-2005 Summary: (Taken from the application): Neonatal lupus is currently considered a model of passively acquired autoimmunity whereby immune abnormalities in the mother (who may have systemic lupus erythematosus, Sjogrens syndrome, or be entirely asymptomatic) lead to the production of antibodies to the SSA/Ro-SSB/La ribonucleoproteins which cross the placenta and presumably injure the developing fetus. The most serious manifestation is cardiac injury which includes varying degrees of atrioventricular (AV) block, most often third degree, and myocarditis. The mortality approaches 20% and the majority of children require lifelong pacing. This application focuses both on the clinical approach to diagnosed congenital heart block (CHB) [interventional study] and the search for an early echocardiographic marker of injury [observational study]. In Specific Aim 1, a randomized double-blind placebo-controlled trial will examine the effect of daily oral dexamethasone (4 mg) on the outcome of CHB. The rationale rests on the hypothesis that CHB is the consequence of an inflammatory process mediated by maternal anti-Ro/La antibodies. Mothers, irrespective of disease activity but requiring less than 10 mg prednisone/day, identified before 30 weeks of gestation to be carrying a fetus with CHB, will be randomized to receive dexamethasone or placebo (50 patients per arm) for a minimum of 6 weeks. Primary outcome measures include neonatal ventricular rate and ejection fraction at birth, and presence or absence of abnormal fluid collection as assessed on the final fetal echocardiogram before delivery. Secondary outcome measures include the degree of block at birth, gestational age, birth weight, and cardiothoracic ratio. In Specific Aim 2, we will attempt to identify the earliest noninvasive echocardiographic marker of AV nodal dysfunction and/or myocardial injury. At present it is not known whether injury to the AV node progresses through stages with the final outcome being fibrosis of the node and irreversible third degree block. It has been proposed that global inflammation of the working myocardium and surrounding pericardium may precede or accompany AV nodal injury. One hundred pregnant women considered at high risk for having a child with CHB, as defined by presence of Ro/La antibodies documented prior to pregnancy (regardless of whether or not they have had a previous child with neonatal lupus), will be followed by weekly echocardiograms from 16 weeks of gestation, with special attention to prolongation of the mechanical PR interval and/or development of myocardial dysfunction. Mothers whose fetuses develop 1st, 2nd or 3rd degree block will then be randomized to receive either dexamethasone or placebo as part of Specific Aim 1. The importance of this second aim is twofold: first, it will identify whether the subclinical incidence of tissue injury exceeds overt injury manifest as advanced AV dissociation; and second, it will provide the best chance for reversibility of block given identification of early lesions. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen
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Project Title: THE ALPHA-1C CALCIUM CHANNEL IN MUSCLE Principal Investigator & Institution: Palade, Philip T.; Physiology and Biophysics; University of Texas Medical Br Galveston 301 University Blvd Galveston, Tx 77555
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Timing: Fiscal Year 2002; Project Start 27-SEP-2000; Project End 31-JUL-2005 Summary: (Adapted from the applicant's abstract): L-type voltage-gated calcium channels also known as dihydropyridine receptors (DHPRs) are critical for excitationcontraction coupling in both skeletal and cardiac muscle. Each of these muscle types expresses its own isoform of the DHPR. The role of the alpha1C cardiac DHPR in cardiac muscle is unquestionable to both provide the influx of Ca2+ needed to trigger Ca2+ release from intracellular stores as well as to provide a means to refill those stores when they become depleted. In vascular smooth muscle these same channels are the site of action of nearly all Ca2+ channel blockers used therapeutically in the treatment of hypertension and heart disease. Recently certain adult skeletal muscles have been shown to exhibit not only the alpha1S skeletal isoform of the DHPR, but also the alpha1C cardiac isoform, although at lower levels of expression. This grant tests several hypotheses for the role of the cardiac DHPR in adult skeletal muscle. The hypotheses to be tested include refilling of partially depleted intracellular Ca2+ stores, forestalling fatigue, and serving to turn off other genes. Methods will include tension, (Ca2+)i and electrophysiology measurements and measurements of gene expression. The results may suggest additional roles for the alpha1C cardiac DHPRs in the heart as well as in many smooth muscles. This grant also seeks to determine how the steroid hormone dexamethasone, the protein kinase C inhibitor staurosporine, and electrical stimulation regulate the expression of the cardiac DHPR in muscle, and to determine the response elements for the transcription factors involved and for tissue-specific expression within the gene promoter. Additional methods will include traditional assays used for promoter work. These results will enhance understanding of the transcriptional regulation of this extremely important receptor for therapeutic agents in the treatment of hypertension and heart disease. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •
Project Title: THE DEVELOPMENT
EFFECTS
OF
DEXAMETHASONE
ON
FOLLICULAR
Principal Investigator & Institution: Rockwell, Laura C.; Anthropology; Temple University 406 Usb, 083-45 Philadelphia, Pa 19122 Timing: Fiscal Year 2001; Project Start 30-SEP-2000; Project End 31-AUG-2004 Summary: Interaction between the hypothalamic-pituitary-adrenal axis (HPA) and the hypothalamic-pituitary-ovarian axis (HPO) is well established but best understood at the level of the central nervous system (CNS) where the adrenal axis has an inhibitory influence on the reproductive axis. Data from our preliminary studies and isolated observations from previously published work, however, indicate that glucocorticoids can, alternatively, enhance reproductive function, likely due to a direct effect of on the ovary. When dexamethasone was administered during the PMSG/hCG priming regimen to immature rats the result was an increase over controls in litter size, ova shed and number of preantral and antral follicles just prior to the endogenous LH surge. Because dexamethasone regulates both Bcl-2 proteins and IAPs in other cells and tissues we surmise that these particular intracellular proteins, mediators of apoptosis in the follicle, may be the key to deciphering how glucocorticoids effect follicular development. We hypothesize that the effect of dexamethasone in the ovary is to suppress atresia in antral follicles and thus increase the number of follicles that ovulate in response to hCG (endogenous analog for LH). The project will evaluate whether dexamethasone acts directly on the ovary to alter follicular development during the priming/treatment period such that a larger crop of follicles ovulates. Three studies will be conducted. The first will evaluate the number of healthy versus atretic ovarian
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follicle, at 3 stages of follicular growth, at 6 time points following either gonadotropin priming (controls) or gonadotropin priming in combination with dexamethasone treatment of animals. In a second series of studies we will determine whether dexamethasone's effects on ovulation are present in hypophysectomized animals. Finally, we will harvest ovarian tissue from which to extract total RNA to assay mRNA expression of Bcl-2 genes from control and DEX treated animals. If dexamethasone treatment alters Bcl-2 mRNA expression in the rat ovary we will examine protein expression and localization using western blot analysis and immunocytochemistry. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •
Project Title: TRAIL APOPTOTIC PATHWAY IN ESOPHAGEAL CANCER Principal Investigator & Institution: El-Deiry, Wafik S.; Associate Professor; University of Pennsylvania 3451 Walnut Street Philadelphia, Pa 19104 Timing: Fiscal Year 2003; Project Start 15-AUG-2003; Project End 30-JUN-2008 Summary: The discovery of TRAIL and its receptors is providing insights into mechanisms of tumor suppression in vivo as well as hope for the development of novel cancer therapies. TRAIL (Tumor Necrosis Factor Related Apoptosis Inducing Ligand) is a potent inducer of cancer but not most normal cell death. Ongoing work in this laboratory has identified one of the TRAIL receptors, KILLER/DR5, as a p53 target gene which can also be regulated by p53-independent pathways including dexamethasone, Interferon gamma and bile acids. We and others have identified possible mechanisms of cancer cell resistance to killing by TRAIL including loss of pro-apoptotic TRAIL receptor expression (DR4) in nasopharyngeal and other cancers, increase of anti apoptotic TRAIL decoy receptor expression in gastrointestinal cancers (TRID), and increased cFLIP expression or loss of caspase 8 expression through hypermethylation in neuroblastoma. The utility of TRAIL has not been explored in Esophageal Squamous Cell Cancer (ESCC). We have preliminary evidence that TRAIL can effectively induce apoptotic death in ESCC and that in some cases Bcl-XL over expression may be uniquely contributing to TRAIL resistance in ESCC. Bcl-XL was also recently recovered by our group as an inhibitor of TRAIL in a genetic screen using colorectal cancer cells and we have found that Bax-/- colon cancer cells are TRAIL resistant. Our current proposal has the following goals to address the hypothesis that TRAIL may be useful in ESCC therapy and that defects in TRAIL signaling may contribute to therapeutic resistance in ESCC: Specific Aim #1: To delineate the mechanisms of TRAIL sensitivity and resistance in esophageal cancer. Specific Aim #2: Investigate the role of TRAIL receptors in p53mediated cell death and chemosensitivity in esophageal cancer and normal esophagus. Specific Aim #3: Investigate the physiological consequences of targeting TRAIL decoy expression to esophageal epithelium. Specific Aim #4: Investigate the consequences of manipulation of the TRAIL pathway in an esophagus reconstruction model. Our studies should provide important insights into the involvement of the TRAIL death pathway and downstream signals in esophageal cancer and susceptibility to TRAIL-induced apoptosis. We will take advantage of integrated approaches with Projects 1 and 2, along with use of the core facilities. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen
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Project Title: TRANSCRIPTIONAL MECHANISMS OF HIPPOCAMPAL AGING Principal Investigator & Institution: Lund, Pauline K.; Professor in Physiology, Pediatrics And; University of North Carolina Chapel Hill Office of Sponsored Research Chapel Hill, Nc 27599
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Timing: Fiscal Year 2002; Project Start 01-AUG-1991; Project End 30-NOV-2006 Summary: Glucocorticoids are implicated as causative factors in age-related cognitive decline. Prior and preliminary data support a central hypothesis that aged, cognitively impaired Long-Evans rats (AI) exhibit more potent (GR) mediated transcription of hippocampal genes associated with neuronal dysfunction or degeneration than young (Y) or aged unimpaired (AU) rats. Specific aims will use unchallenged rats and rats with elevated circulating glucocorticoid induced by stress, corticosterone or dexamethasone administration. Wild type mice and NF-kappaB-p50 null mice will serve as useful controls in aims 2 and 3. Hippocampal glucocorticoid receptor transcription complexes will be characterized and quantified by electromobility gel shift, western immunoblot and co- immunoprecipitation assays. Gene expression profiles will be assessed using Genechip microarrays. Aim #1: will test the hypothesis that AI rats exhibit elevated GR mediated transcription and have higher levels of active GR relate to MR. Aim #2: will test the hypothesis that AI rats exhibit reduced association of NF-kappaB (NF-kappaB) with GR and develop approaches to functionally inhibit GR: NF-kappaB interaction. Aim #3 will test if cholinergic input from the basal forebrain regulates levels of GR, MR, GRE binding activity or composition. Findings from gene microarray experiments are relevant to all sub- projects of the PPG but this project has particular interactions with and relevance to sub-projects #2 and #4. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •
Project Title: TWIN STUDY OF BIOLOGIC MARKERS FOR PTSD Principal Investigator & Institution: Pitman, Roger K.; Massachusetts General Hospital 55 Fruit St Boston, Ma 02114
Associate
Professor;
Timing: Fiscal Year 2002; Project Start 30-SEP-1995; Project End 31-MAY-2007 Summary: (provided by applicant): This project will take advantage of the unique opportunity to follow up a successful investigation of the origin of elevated responses to sudden, loud tones in post-traumatic stress disorder (PTSD) in a population of identical twins discordant for combat exposure in Vietnam. The proposed study will evaluate the origin of two additional putative PTSD biologic markers that reflect amygdala hyper (re)activity in PTSD. The possible marker origins to be addressed are: a.) Familial vulnerability for PTSD, vs. b.) acquired PTSD sign. Familial vulnerability will be evaluated by comparing the (high-risk) non-combat-exposed co-twins of combatexposed twins with PTSD vs. the (low-risk) non-combat-exposed co-twins of combatexposed twins without PTSD. Acquired PTSD sign will be evaluated by examining the interaction between a between-pair PTSD Diagnostic status factor PTSD vs. non-PTSD in the combat-exposed twin) and a within-pair Exposure factor (combat vs. non-combat). Dependent variables (markers) will include a.) Strength of acquisition and extinction of a classically conditioned differential skin conductance response, i.e., "conditionability," and b.) functional magnetic resonance imaging (fMRI) amygdala response to "masked" presentations of fearful facial expressions. Each marker is non-invasive; can be measured on an ambulatory basis; has been shown in previous, published, peerreviewed research to significantly differentiate PTSD and non-PTSD subject groups; and is capable of being informed by the data to be obtained in the proposed project. Twin subject pairs will travel to the Massachusetts General Hospital for a long weekend to undergo psychodiagnostic and psychometric evaluation, and the conditionability and fMRI masked faces procedures. Statistical significance will be tested by means of analyses of variance and covariance, a priori t-tests, and correlational analyses. Results are expected to advance our understanding of the constitutional vs. acquired nature of biologic abnormalities in PTSD and the neuroanatomy and pathogenesis of this
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disorder. Results may also have implications for the prophylactic screening of persons at high risk for the development of PTSD upon exposure to military combat or other severe stressors. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •
Project Title: VITAMIN D AND DEXAMETHASONE IN MYELODYSPLASTIC SYNDROMES Principal Investigator & Institution: Redner, Robert L.; Associate Professor of Medicine; Medicine; University of Pittsburgh at Pittsburgh 350 Thackeray Hall Pittsburgh, Pa 15260 Timing: Fiscal Year 2002; Project Start 30-SEP-2002; Project End 31-AUG-2004 Summary: (provided by applicant): The myelodysplastic syndromes (MDS) represent a heterogeneous group of diseases that manifest themselves as dyspoiesis. Abnormal clonal development of hematopoietic progenitors in MDS leads to severe cytopenias and a predisposition to develop acute myelogenous leukemia. Current therapeutic options for MDS are limited, and aside from bone marrow transplantation, none have proven superior to supportive measures alone. Preclinical investigations have indicated a potential therapeutic role for vitamin D in treatment of MDS. However, because of doselimiting toxicity of hypercalcemia, clinical trials with vitamin D have used low doses, with promising but inconsistent results. We have developed a dosing schema of Dexamethasone and calcitriol (the active form of vitamin D) that augments the therapeutic index of calcitriol, and allows for safe administration of 5-10 times higher doses of calcitriol than has previously been used for MDS. We have also determined that Dexamethasone potentiates the activity of vitamin D in a number of preclinical models for squamous cell carcinoma and prostate cancer. In this proposal we will test the hypothesis that the combination of Dex and high-dose calcitriol will be effective for treatment of MDS. We propose herein a phase II trial of Dex and calcitriol for MDS. This trial will analyze hematologic response and toxicity. Bone marrow samples will be serially analyzed for differentiation, cell cycle arrest, and apoptosis. The in vitro studies will be correlated with in vivo response. Our hope is that these studies will help us develop a potentially novel, oral, minimally toxic regimen for treating MDS. 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 “dexamethasone” (or synonyms) into the search box. This search gives you access to full-text articles. The following is a sample of items found for dexamethasone in the PubMed Central database: 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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A correlation between dexamethasone inducibility and basal expression levels of retroviral vector proviruses. by Duch M, Paludan K, Lovmand J, Pedersen L, Jorgensen P, Pedersen FS.; 1993 Oct 11; http://www.pubmedcentral.gov/picrender.fcgi?tool=pmcentrez&action=stream&blobt ype=pdf&artid=331505
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Budesonide epimer R or dexamethasone selectively inhibit platelet-activating factorinduced or interleukin 1[beta]-induced DNA binding activity of cis-acting transcription factors and cyclooxygenase-2 gene expression in human epidermal keratinocytes. by Lukiw WJ, Pelaez RP, Martinez J, Bazan NG.; 1998 Mar 31; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=19937
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Characterization of dexamethasone-induced reactivation of latent bovine herpesvirus 1. by Rock D, Lokensgard J, Lewis T, Kutish G.; 1992 Apr; http://www.pubmedcentral.gov/picrender.fcgi?tool=pmcentrez&action=stream&blobt ype=pdf&artid=289044
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Chronic administration of dexamethasone results in Fc receptor up-regulation and inhibition of class I antigen expression on macrophages from MRL/lpr autoimmune mice. by Zuckerman SH, Evans GF, Bryan N.; 1997 Sep; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&rendertype=abstr act&artid=170598
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Concentrations of ceftriaxone in cerebrospinal fluid of children with meningitis receiving dexamethasone therapy. by Gaillard JL, Abadie V, Cheron G, Lacaille F, Mahut B, Silly C, Matha V, Coustere C, Lokiec F.; 1994 May; http://www.pubmedcentral.gov/picrender.fcgi?tool=pmcentrez&action=stream&blobt ype=pdf&artid=188183
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Cyclosporin A Potentiates the Dexamethasone-Induced Mouse Mammary Tumor Virus-Chloramphenicol Acetyltransferase Activity in LMCAT Cells: A Possible Role for Different Heat Shock Protein-Binding Immunophilins in Glucocorticosteroid Receptor-Mediated Gene Expression. by Renoir J, Mercier-Bodard C, Hoffmann K, Bihan SL, Ning Y, Sanchez ER, Handschumacher RE, Baulieu E.; 1995 May 23; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&rendertype=abstr act&artid=41830
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Cytoplasmic Phospholipase A2 Activity and Gene Expression are Stimulated by Tumor Necrosis Factor: Dexamethasone Blocks the Induced Synthesis. by Hoeck WG, Ramesha CS, Chang DJ, Fan N, Heller RA.; 1993 May 15; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&rendertype=abstr act&artid=46534
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Dexamethasone Causes Sustained Expression of Mitogen-Activated Protein Kinase (MAPK) Phosphatase 1 and Phosphatase-Mediated Inhibition of MAPK p38. by Lasa M, Abraham SM, Boucheron C, Saklatvala J, Clark AR.; 2002 Nov; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=134716
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Dexamethasone Destabilizes Cyclooxygenase 2 mRNA by Inhibiting MitogenActivated Protein Kinase p38. by Lasa M, Brook M, Saklatvala J, Clark AR.; 2001 Feb 1; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=86669
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Dexamethasone in adults with bacterial meningitis. by Suh KN.; 2003 Mar 18; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=154925
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Dexamethasone inducible gene expression optimised by glucocorticoid antagonists. by Mikulits W, Chen D, Mullner EW.; 1995 Jun 25; http://www.pubmedcentral.gov/picrender.fcgi?tool=pmcentrez&action=stream&blobt ype=pdf&artid=307029
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Dexamethasone Induction of the Intracellular RNAs of Mouse Mammary Tumor Virus. by Robertson DL, Varmus HE.; 1981 Dec; http://www.pubmedcentral.gov/picrender.fcgi?tool=pmcentrez&action=stream&blobt ype=pdf&artid=256679
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Dexamethasone inhibits alpha-fetoprotein gene transcription in neonatal rat liver and isolated nuclei. by Huang DP, Cote GJ, Massari RJ, Chiu JF.; 1985 Jun 11; http://www.pubmedcentral.gov/picrender.fcgi?tool=pmcentrez&action=stream&blobt ype=pdf&artid=341283
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Dexamethasone Negatively Regulates the Activity of a Chimeric Dihydrofolate Reductase/Glucocorticoid Receptor Protein. by Israel DI, Kaufman RJ.; 1993 May 1; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&rendertype=abstr act&artid=46492
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Dexamethasone Responsiveness of a Major Glucocorticoid-Inducible CYP3A Gene is Mediated by Elements Unrelated to a Glucocorticoid Receptor Binding Motif. by Huss JM, Wang SI, Astrom A, McQuiddy P, Kasper CB.; 1996 May 14; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&rendertype=abstr act&artid=39336
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Dexamethasone stimulates expression of transposable type A intracisternal retroviruslike genes in mouse (Mus musculus) cells. by Emanoil-Ravier R, Mercier G, Canivet M, Garcette M, Lasneret J, Peronnet F, Best-Belpomme M, Peries J.; 1988 Oct; http://www.pubmedcentral.gov/picrender.fcgi?tool=pmcentrez&action=stream&blobt ype=pdf&artid=253534
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Dexamethasone, a Drug for Attenuation of Schistosoma mansoni Infection Morbidity. by Pyrrho AD, Ramos JA, Neto RM, Silva CS, Lenzi HL, Takiya CM, Gattass CR.; 2002 Nov; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=128711
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Dexamethasone-stimulated expression of a proviral copy of mouse mammary tumor virus env mRNA. by Robertson DL.; 1984 May; http://www.pubmedcentral.gov/picrender.fcgi?tool=pmcentrez&action=stream&blobt ype=pdf&artid=255691
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Differential effects of nerve growth factor and dexamethasone on herpes simplex virus type 1 oriL- and oriS-dependent DNA replication in PC12 cells. by Hardwicke MA, Schaffer PA.; 1997 May; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&rendertype=abstr act&artid=191505
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Effect of dexamethasone on detection of herpes simplex virus in clinical specimens by conventional cell culture and rapid 24-well plate centrifugation. by Woods GL, Mills RD.; 1988 Jun; http://www.pubmedcentral.gov/picrender.fcgi?tool=pmcentrez&action=stream&blobt ype=pdf&artid=266572
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Effect of dexamethasone on therapy of experimental penicillin- and cephalosporinresistant pneumococcal meningitis. by Paris MM, Hickey SM, Uscher MI, Shelton S, Olsen KD, McCracken GH Jr.; 1994 Jun; http://www.pubmedcentral.gov/picrender.fcgi?tool=pmcentrez&action=stream&blobt ype=pdf&artid=188205
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Effect of dexamethasone or HWA-138 in combination with antibiotics in experimental Haemophilus influenzae type b infection. by Rodriguez AF, Kaplan SL, Hawkins EP, Mason EO Jr.; 1991 Oct; http://www.pubmedcentral.gov/picrender.fcgi?tool=pmcentrez&action=stream&blobt ype=pdf&artid=245311
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Effect of treatment of shell vial cell cultures with dimethyl sulfoxide and dexamethasone for detection of cytomegalovirus. by Espy MJ, Wold AD, Ilstrup DM, Smith TF.; 1988 Jun; http://www.pubmedcentral.gov/picrender.fcgi?tool=pmcentrez&action=stream&blobt ype=pdf&artid=266538
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Effect of xanthine derivates and dexamethasone on Streptococcus pneumoniaestimulated production of tumor necrosis factor alpha, interleukin-1 beta (IL-1 beta), and IL-10 by human leukocytes. by van Furth AM, Seijmonsbergen EM, Langermans JA, van der Meide PH, van Furth R.; 1995 Nov; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&rendertype=abstr act&artid=170221
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Effects of dexamethasone on human natural killer cell cytotoxicity, interferon production, and interleukin-2 receptor expression induced by microbial antigens. by Piccolella E, Lombardi G, Vismara D, Del Gallo F, Colizzi V, Dolei A, Dianzani F.; 1986 Feb; http://www.pubmedcentral.gov/picrender.fcgi?tool=pmcentrez&action=stream&blobt ype=pdf&artid=262419
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Effects of intravitreal dexamethasone on concentration of intravitreal vancomycin in experimental methicillin-resistant Staphylococcus epidermidis endophthalmitis. by Smith MA, Sorenson JA, Smith C, Miller M, Borenstein M.; 1991 Jul; http://www.pubmedcentral.gov/picrender.fcgi?tool=pmcentrez&action=stream&blobt ype=pdf&artid=245161
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Effects of pentoxifylline or dexamethasone in combination with amphotericin B in experimental murine cerebral cryptococcosis: evidence of neuroexcitatory pathogenic mechanisms. by Ostrosky-Zeichner L, Soto-Hernandez JL, Angeles-Morales V, Teixeira F, Nava-Ruiz C, Rios C, Solis F, Sotelo J.; 1996 May; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&rendertype=abstr act&artid=163290
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Enhanced detection of cytomegalovirus in confluent MRC-5 cells treated with dexamethasone and dimethyl sulfoxide. by West PG, Aldrich B, Hartwig R, Haller GJ.; 1988 Dec; http://www.pubmedcentral.gov/picrender.fcgi?tool=pmcentrez&action=stream&blobt ype=pdf&artid=266935
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Enhancement by calcium of the detection of cytomegalovirus in cells treated with dexamethasone and dimethyl sulfoxide. by West PG, Baker WW.; 1990 Aug; http://www.pubmedcentral.gov/picrender.fcgi?tool=pmcentrez&action=stream&blobt ype=pdf&artid=268033
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Evaluation of curative anticryptosporidial activity of paromomycin in a dexamethasone-treated rat model. by Verdon R, Polianski J, Gaudebout C, Marche C, Garry L, Pocidalo JJ.; 1994 Jul; http://www.pubmedcentral.gov/picrender.fcgi?tool=pmcentrez&action=stream&blobt ype=pdf&artid=284618
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Evaluation of high-dose regimen of paromomycin against cryptosporidiosis in the dexamethasone-treated rat model. by Verdon R, Polianski J, Gaudebout C, Marche C, Garry L, Carbon C, Pocidalo JJ.; 1995 Sep; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&rendertype=abstr act&artid=162902
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Evidence of Less Severe Aortic Valve Destruction after Treatment of Experimental Staphylococcal Endocarditis with Vancomycin and Dexamethasone. by Siaperas P, Pefanis A, Iliopoulos D, Katsarolis I, Kyroudi-Voulgari A, Donta I, Karayiannakos P, Giamarellou H.; 2001 Dec; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=90864
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Identification of a Novel Dexamethasone-Sensitive RNA-Destabilizing Region on Rat Monocyte Chemoattractant Protein 1 mRNA. by Poon M, Liu B, Taubman MB.; 1999 Oct; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=84617
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In the Presence of Dexamethasone, [gamma] Interferon Induces Rat Oligodendrocytes to Express Major Histocompatibility Complex Class II Molecules. by Bergsteinsdottir K, Brennan A, Jessen KR, Mirsky R.; 1992 Oct 1; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&rendertype=abstr act&artid=50063
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Increased detection of herpes simplex virus in MRC-5 cells treated with dimethyl sulfoxide and dexamethasone. by West PG, Aldrich B, Hartwig R, Haller GJ.; 1989 Apr; http://www.pubmedcentral.gov/picrender.fcgi?tool=pmcentrez&action=stream&blobt ype=pdf&artid=267415
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Influence of dexamethasone on efficacy of ceftriaxone and vancomycin therapy in experimental pneumococcal meningitis. by Cabellos C, Martinez-Lacasa J, Martos A, Tubau F, Fernandez A, Viladrich PF, Gudiol F.; 1995 Sep; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&rendertype=abstr act&artid=162903
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Inhibition of lipopolysaccharide-induced transcription factor Sp1 binding by spectrally pure diphosphoryl lipid A from Rhodobacter sphaeroides, protein kinase inhibitor H-8, and dexamethasone. by Jarvis BW, Qureshi N.; 1997 May; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&rendertype=abstr act&artid=175189
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Lipocortin 1 Mediates Dexamethasone-Induced Growth Arrest of the A549 Lung Adenocarcinoma Cell Line. by Croxtall JD, Flower RJ.; 1992 Apr 15; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&rendertype=abstr act&artid=48910
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Lipocortin 1 Mediates the Inhibition by Dexamethasone of the Induction by Endotoxin of Nitric Oxide Synthase in the Rat. by Wu C, Croxtall JD, Perretti M, Bryant CE, Thiemermann C, Flower RJ, Vane JR.; 1995 Apr 11; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&rendertype=abstr act&artid=42189
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Low doses of dexamethasone decrease brain water content of collagenase-induced cerebral hematoma. by Vachon P, Moreau JP.; 2003 May; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=227046
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Low-dose dexamethasone as adjunctive therapy for disseminated Mycobacterium avium complex infections in AIDS patients. by Wormser GP, Horowitz H, Dworkin B.; 1994 Sep; http://www.pubmedcentral.gov/picrender.fcgi?tool=pmcentrez&action=stream&blobt ype=pdf&artid=284717
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Low-dose dexamethasone challenge in women with atypical major depression: pilot study. by Levitan RD, Vaccarino FJ, Brown GM, Kennedy SH.; 2002 Jan; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=149795
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Modulation of Mycoplasma arthritidis-derived superantigen-induced cytokine gene expression by dexamethasone and interleukin-4. by Mehindate K, al-Daccak R, Rink L, Mecheri S, Hebert J, Mourad W.; 1994 Nov; http://www.pubmedcentral.gov/picrender.fcgi?tool=pmcentrez&action=stream&blobt ype=pdf&artid=303178
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Molecular Mechanisms of Dexamethasone Inhibition of Nitric Oxide Synthase Expression in Interleukin 1[beta]-Stimulated Mesangial Cells: Evidence for the Involvement of Transcriptional and Posttranscriptional Regulation. by Kunz D, Walker G, Eberhardt W, Pfeilschifter J.; 1996 Jan 9; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&rendertype=abstr act&artid=40217
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Paradoxical Transcriptional Activation of Rat Liver Cytochrome P-450 3A1 by Dexamethasone and the Antiglucocorticoid Pregnenolone 16[alpha]- Carbonitrile: Analysis by Transient Transfection into Primary Monolayer Cultures of Adult Rat Hepatocytes. by Burger H, Schuetz JD, Schuetz EG, Guzelian PS.; 1992 Mar 15; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&rendertype=abstr act&artid=48613
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Regulation of Cysteine-Rich Intestinal Protein by Dexamethasone in the Neonatal Rat. by Levenson CW, Shay NF, Lee-Ambrose LM, Cousins RJ.; 1993 Jan 15; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&rendertype=abstr act&artid=45735
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Rhesus papillomavirus type 1 cooperates with activated ras in transforming primary epithelial rat cells independent of dexamethasone. by Schneider JF, McGlennen RC, LaBresh KV, Ostrow RS, Faras AJ.; 1991 Jun; http://www.pubmedcentral.gov/picrender.fcgi?tool=pmcentrez&action=stream&blobt ype=pdf&artid=240996
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Role of lipopolysaccharide (LPS), interleukin-1, interleukin-6, tumor necrosis factor, and dexamethasone in regulation of LPS-binding protein expression in normal hepatocytes and hepatocytes from LPS-treated rats. by Wan Y, Freeswick PD, Khemlani LS, Kispert PH, Wang SC, Su GL, Billiar TR.; 1995 Jul; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&rendertype=abstr act&artid=173325
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Staphylococcal Enterotoxin B-Induced Acute Inflammation Is Inhibited by Dexamethasone: Important Role of CXC Chemokines KC and Macrophage Inflammatory Protein 2. by Schramm R, Thorlacius H.; 2003 May; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=153246
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Superantigens and Cystic Fibrosis: Resistance of Presenting Cells to Dexamethasone. by Ben-Ari J, Gozal D, Dorio RJ, Bowman CM, Reiff A, Walker SM.; 2000 Jul; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=95912
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Superiority of methylprednisolone over dexamethasone for induction of Pneumocystis carinii infection in rats. by Sukura A, Soveri T, Lindberg LA.; 1991 Oct; http://www.pubmedcentral.gov/picrender.fcgi?tool=pmcentrez&action=stream&blobt ype=pdf&artid=270323
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The alpha-foetoprotein proximal enhancer: localization, cell specificity and modulation by dexamethasone. by Houart C, Szpirer J, Szpirer C.; 1990 Nov 11; http://www.pubmedcentral.gov/picrender.fcgi?tool=pmcentrez&action=stream&blobt ype=pdf&artid=332492
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 dexamethasone, simply go to the PubMed Web site at http://www.ncbi.nlm.nih.gov/pubmed. Type “dexamethasone” (or synonyms) into the search box, and click “Go.” The following is the type of output you can expect from PubMed for dexamethasone (hyperlinks lead to article summaries): •
A C-1291G polymorphism in the alpha2A-adrenergic receptor gene (ADRA2A) promoter is associated with cortisol escape from dexamethasone and elevated glucose levels. Author(s): Rosmond R, Bouchard C, Bjorntorp P. Source: Journal of Internal Medicine. 2002 March; 251(3): 252-7. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11886485&dopt=Abstract
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A case of cutaneous delayed-type allergy to oral dexamethasone and to betamethasone. Author(s): Nucera E, Buonomo A, Pollastrini E, De Pasquale T, Del Ninno M, Roncallo C, Schiavino D, Patriarca G. Source: Dermatology (Basel, Switzerland). 2002; 204(3): 248-50. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12037457&dopt=Abstract
6 PubMed was developed by the National Center for Biotechnology Information (NCBI) at the National Library of Medicine (NLM) at the National Institutes of Health (NIH). The PubMed database was developed in conjunction with publishers of biomedical literature as a search tool for accessing literature citations and linking to full-text journal articles at Web sites of participating publishers. Publishers that participate in PubMed supply NLM with their citations electronically prior to or at the time of publication.
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A combination of dexamethasone, cyclophosphamide, etoposide, and cisplatin is less toxic and more effective than high-dose cyclophosphamide for peripheral stem cell mobilization in multiple myeloma. Author(s): Corso A, Arcaini L, Caberlon S, Zappasodi P, Mangiacavalli S, Lorenzi A, Rusconi C, Troletti D, Maiocchi MA, Pascutto C, Morra E, Lazzarino M. Source: Haematologica. 2002 October; 87(10): 1041-5. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12368158&dopt=Abstract
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A comparison of dexamethasone, ondansetron, and dexamethasone plus ondansetron as prophylactic antiemetic and antipruritic therapy in patients receiving intrathecal morphine for major orthopedic surgery. Author(s): Szarvas S, Chellapuri RS, Harmon DC, Owens J, Murphy D, Shorten GD. Source: Anesthesia and Analgesia. 2003 July; 97(1): 259-63, Table of Contents. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12818978&dopt=Abstract
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A dexamethasone, vinblastine, cyclophosphamide, etoposide, methotrexate and bleomycin (D-VICEMB) protocol as first-line treatment of patients aged 70 years or older affected by intermediate/high grade non-Hodgkin's lymphoma. Author(s): Angrilli F, Pennese E, Di Marzio A, Liberatore E, Di Lorenzo R, Fioritoni G. Source: Haematologica. 2002 November; 87(11): 1227-9. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12414356&dopt=Abstract
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A new multidrug reinduction protocol with topotecan, vinorelbine, thiotepa, dexamethasone, and gemcitabine for relapsed or refractory acute leukemia. Author(s): Kolb EA, Steinherz PG. Source: Leukemia : Official Journal of the Leukemia Society of America, Leukemia Research Fund, U.K. 2003 October; 17(10): 1967-72. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=14513046&dopt=Abstract
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A Phase II trial of pegylated liposomal doxorubicin, vincristine, and reduced-dose dexamethasone combination therapy in newly diagnosed multiple myeloma patients. Author(s): Hussein MA, Wood L, Hsi E, Srkalovic G, Karam M, Elson P, Bukowski RM. Source: Cancer. 2002 November 15; 95(10): 2160-8. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12412170&dopt=Abstract
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A prospective randomized trial of megadose methylprednisolone and high dose dexamethasone for traumatic optic neuropathy. Author(s): Chuenkongkaew W, Chirapapaisan N. Source: J Med Assoc Thai. 2002 May; 85(5): 597-603. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12188391&dopt=Abstract
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A prospective, open-label trial assessing dexamethasone pulse therapy in moderate to severe ulcerative colitis. Author(s): Sood A, Midha V, Sood N, Awasthi G. Source: Journal of Clinical Gastroenterology. 2002 October; 35(4): 328-31. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12352296&dopt=Abstract
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A pulse of insulin and dexamethasone stimulates serum leptin in fasting human subjects. Author(s): Laferrere B, Caixas A, Fried SK, Bashore C, Kim J, Pi-Sunyer FX. Source: European Journal of Endocrinology / European Federation of Endocrine Societies. 2002 June; 146(6): 839-45. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12039705&dopt=Abstract
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A randomized double-blind trial to compare the clinical efficacy of granisetron with metoclopramide, both combined with dexamethasone in the prophylaxis of chemotherapy-induced delayed emesis. Author(s): Aapro MS, Thuerlimann B, Sessa C, De Pree C, Bernhard J, Maibach R; Swiss Group for Clinical Cancer Research. Source: Annals of Oncology : Official Journal of the European Society for Medical Oncology / Esmo. 2003 February; 14(2): 291-7. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12562658&dopt=Abstract
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A randomized, double-blind, placebo-controlled trial of dexamethasone in severe respiratory syncytial virus (RSV) infection: effects on RSV quantity and clinical outcome. Author(s): Buckingham SC, Jafri HS, Bush AJ, Carubelli CM, Sheeran P, Hardy RD, Ottolini MG, Ramilo O, DeVincenzo JP. Source: The Journal of Infectious Diseases. 2002 May 1; 185(9): 1222-8. Epub 2002 April 16. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12001038&dopt=Abstract
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A reappraisal of the ovine corticotropin-releasing hormone stimulation test in the differential diagnosis of Cushing's syndrome: a comparison with the standard highdose dexamethasone suppression test. Author(s): Lee TI, Lin SY, Won JG, Tang KT, Jap TS, Kwok CF, Lin HD. Source: Zhonghua Yi Xue Za Zhi (Taipei). 2002 October; 65(10): 474-82. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12523812&dopt=Abstract
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A synthetic corticosteroid, dexamethasone regulates generation of soluble form of interleukin-6 receptor of human lymphocytes, in vitro. Author(s): Polgar A, Brozik M, Toth S, Holub M, Falus A. Source: Acta Biol Hung. 2002; 53(3): 307-15. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12371610&dopt=Abstract
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A taste comparison of three different liquid steroid preparations: prednisone, prednisolone, and dexamethasone. Author(s): Mitchell JC, Counselman FL. Source: Academic Emergency Medicine : Official Journal of the Society for Academic Emergency Medicine. 2003 April; 10(4): 400-3. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12670859&dopt=Abstract
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A three year follow up of preterm infants after moderately early treatment with dexamethasone. Author(s): Romagnoli C, Zecca E, Luciano R, Torrioli G, Tortorolo G. Source: Archives of Disease in Childhood. Fetal and Neonatal Edition. 2002 July; 87(1): F55-8. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12091294&dopt=Abstract
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Activation of anchorage-independent growth of HT1080 human fibrosarcoma cells by dexamethasone. Author(s): Kondoh N, Shuda M, Arai M, Oikawa T, Yamamoto M. Source: In Vitro Cellular & Developmental Biology. Animal. 2002 February; 38(2): 111-7. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11928993&dopt=Abstract
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Acute mast cell-dependent neutrophil recruitment in the skin is mediated by KC and LFA-1: inhibitory mechanisms of dexamethasone. Author(s): Schramm R, Schaefer T, Menger MD, Thorlacius H. Source: Journal of Leukocyte Biology. 2002 December; 72(6): 1122-32. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12488493&dopt=Abstract
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Adjunctive dexamethasone treatment in acute bacterial meningitis. Author(s): Chaudhuri A. Source: Lancet. Neurology. 2004 January; 3(1): 54-62. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=14693112&dopt=Abstract
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Alterations in adult rat heart after neonatal dexamethasone therapy. Author(s): de Vries WB, van der Leij FR, Bakker JM, Kamphuis PJ, van Oosterhout MF, Schipper ME, Smid GB, Bartelds B, van Bel F. Source: Pediatric Research. 2002 December; 52(6): 900-6. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12438668&dopt=Abstract
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An analysis of the antiemetic protection of metoclopramide plus dexamethasone in Chinese patients receiving moderately high emetogenic chemotherapy. Author(s): Molassiotis A, Mok TS, Yam BM, Yung H. Source: European Journal of Cancer Care. 2002 June; 11(2): 108-13. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12099946&dopt=Abstract
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Analgesic effects of dexamethasone in burn injury. Author(s): Werner MU, Lassen B, Kehlet H. Source: Regional Anesthesia and Pain Medicine. 2002 May-June; 27(3): 254-60. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12016598&dopt=Abstract
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Antiemetic effects of granisetron, droperidol and dexamethasone in otologic surgery. Author(s): Goksu S, Kocoglu H, Bayazit YA, Yuksek S, Karci Y, Kanlikama M, Oner U. Source: Auris, Nasus, Larynx. 2002 July; 29(3): 253-6. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12167446&dopt=Abstract
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Antisense p53 transduction leads to overexpression of bcl-2 and dexamethasone resistance in multiple myeloma. Author(s): Iyer R, Ding L, Batchu RB, Naugler S, Shammas MA, Munshi NC. Source: Leukemia Research. 2003 January; 27(1): 73-8. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12479855&dopt=Abstract
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Association of antenatal and postnatal dexamethasone exposure with outcomes in extremely low birth weight neonates. Author(s): LeFlore JL, Salhab WA, Broyles RS, Engle WD. Source: Pediatrics. 2002 August; 110(2 Pt 1): 275-9. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12165578&dopt=Abstract
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Basal levels and patterns of anticancer drug-induced activation of nuclear factorkappaB (NF-kappaB), and its attenuation by tamoxifen, dexamethasone, and curcumin in carcinoma cells. Author(s): Chuang SE, Yeh PY, Lu YS, Lai GM, Liao CM, Gao M, Cheng AL. Source: Biochemical Pharmacology. 2002 May 1; 63(9): 1709-16. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12007574&dopt=Abstract
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Birthsize, gestational age and adrenal function in adult life: studies of dexamethasone suppression and ACTH1-24 stimulation. Author(s): Kajantie E, Eriksson J, Barker DJ, Forsen T, Osmond C, Wood PJ, Andersson S, Dunkel L, Phillips DI. Source: European Journal of Endocrinology / European Federation of Endocrine Societies. 2003 December; 149(6): 569-75. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=14640999&dopt=Abstract
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Bi-weekly epirubicin, etoposide and low-dose dexamethasone for hormone-refractory prostate cancer. Author(s): Odrazka K, Vaculikova M, Petera J, Moravek P, Prosvic P, Zoul Z, Rydel L, Brodak M, Veselsky Z, Louda M, Simakova E. Source: International Journal of Urology : Official Journal of the Japanese Urological Association. 2003 July; 10(7): 387-91. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12823694&dopt=Abstract
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Body composition in infants with chronic lung disease after treatment with dexamethasone. Author(s): Bolt RJ, van Weissenbruch MM, Roos JC, Delemarre-van de Waal HA, Cranendonk A, Lafeber HN. Source: Acta Paediatrica (Oslo, Norway : 1992). 2002; 91(7): 815-21. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12200909&dopt=Abstract
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Bradykinin induces interleukin-6 production in human airway smooth muscle cells: modulation by Th2 cytokines and dexamethasone. Author(s): Huang CD, Tliba O, Panettieri RA Jr, Amrani Y. Source: American Journal of Respiratory Cell and Molecular Biology. 2003 March; 28(3): 330-8. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12594059&dopt=Abstract
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Calcitriol (1,25-dihydroxycholecalciferol) potentiates activity of mitoxantrone/dexamethasone in an androgen independent prostate cancer model. Author(s): Ahmed S, Johnson CS, Rueger RM, Trump DL. Source: The Journal of Urology. 2002 August; 168(2): 756-61. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12131364&dopt=Abstract
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CAR is a cell-cell adhesion protein in human cancer cells and is expressionally modulated by dexamethasone, TNFalpha, and TGFbeta. Author(s): Bruning A, Runnebaum IB. Source: Gene Therapy. 2003 February; 10(3): 198-205. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12571626&dopt=Abstract
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cDNA microarray analysis of gene expression changes induced by dexamethasone in cultured human trabecular meshwork cells. Author(s): Ishibashi T, Takagi Y, Mori K, Naruse S, Nishino H, Yue BY, Kinoshita S. Source: Investigative Ophthalmology & Visual Science. 2002 December; 43(12): 3691-7. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12454038&dopt=Abstract
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Cellular handling of a dexamethasone-anti-E-selectin immunoconjugate by activated endothelial cells: comparison with free dexamethasone. Author(s): Kok RJ, Everts M, Asgeirsdottir SA, Meijer DK, Molema G. Source: Pharmaceutical Research. 2002 November; 19(11): 1730-5. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12458680&dopt=Abstract
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Cellular proliferative effect of dexamethasone in immortalized trabecular meshwork cell (TM5) line. Author(s): Jeon JW, Lee SJ, Kim JB, Kang JJ, Lee JH, Seong GJ, Kim EK. Source: Yonsei Medical Journal. 2003 April 30; 44(2): 299-306. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12728472&dopt=Abstract
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Changes of the physiological parameters of very low-birthweight infants with chronic lung disease treated with dexamethasone. Author(s): Takeuchi T, Tanaka D, Saikawa N, Satoh H, Iwasaki J, Inoue M, Narui K, Iikura Y. Source: Pediatrics International : Official Journal of the Japan Pediatric Society. 2002 April; 44(2): 122-6. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11896866&dopt=Abstract
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Characterization of new selective somatostatin receptor subtype-2 (sst2) antagonists, BIM-23627 and BIM-23454. Effects of BIM-23627 on GH release in anesthetized male rats after short-term high-dose dexamethasone treatment. Author(s): Tulipano G, Soldi D, Bagnasco M, Culler MD, Taylor JE, Cocchi D, Giustina A. Source: Endocrinology. 2002 April; 143(4): 1218-24. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11897676&dopt=Abstract
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Cognitive effects of dexamethasone at high altitude. Author(s): Lafleur J, Giron M, Demarco M, Kennedy R, BeLue R, Shields C. Source: Wilderness Environ Med. 2003 Spring; 14(1): 20-3. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12659245&dopt=Abstract
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Combination therapy with thalidomide plus dexamethasone for newly diagnosed myeloma. Author(s): Rajkumar SV, Hayman S, Gertz MA, Dispenzieri A, Lacy MQ, Greipp PR, Geyer S, Iturria N, Fonseca R, Lust JA, Kyle RA, Witzig TE. Source: Journal of Clinical Oncology : Official Journal of the American Society of Clinical Oncology. 2002 November 1; 20(21): 4319-23. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12409330&dopt=Abstract
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Combined methylprednisolone and dexamethasone therapy for paraquat poisoning. Author(s): Chen GH, Lin JL, Huang YK. Source: Critical Care Medicine. 2002 November; 30(11): 2584-7. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12441774&dopt=Abstract
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Comparative evaluation of diclofenac and dexamethasone following strabismus surgery. Author(s): Dadeya S, Kamlesh. Source: Journal of Pediatric Ophthalmology and Strabismus. 2002 May-June; 39(3): 1668. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12051282&dopt=Abstract
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Comparative study of low-dose oral granisetron plus dexamethasone and high-dose metoclopramide plus dexamethasone in prevention of nausea and vomiting induced by CHOP-therapy in young patients with non-Hodgkin's lymphoma. Author(s): Numbenjapon T, Sriswasdi C, Mongkonsritragoon W, Leelasiri A, Prayoonwiwat W. Source: J Med Assoc Thai. 2002 November; 85(11): 1156-63. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12546311&dopt=Abstract
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Comparison between buserelin and dexamethasone testing in the assessment of hirsutism. Author(s): Re T, Barbetta L, Dall'Asta C, Faglia G, Ambrosi B. Source: J Endocrinol Invest. 2002 January; 25(1): 84-90. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11883870&dopt=Abstract
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Comparison of granisetron and granisetron plus dexamethasone for the prevention of postoperative nausea and vomiting after laparoscopic cholecystectomy. Author(s): Biswas BN, Rudra A. Source: Acta Anaesthesiologica Scandinavica. 2003 January; 47(1): 79-83. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12492802&dopt=Abstract
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Comparison of two different schedules of granulocyte-colony-stimulating factor during treatment for acute lymphocytic leukemia with a hyper-CVAD (cyclophosphamide, doxorubicin, vincristine, and dexamethasone) regimen. Author(s): Weiser MA, O'Brien S, Thomas DA, Pierce SA, Lam TP, Kantarjian HM. Source: Cancer. 2002 January 15; 94(2): 285-91. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11900213&dopt=Abstract
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Complete regression of bone metastases on super bone scan, by low-dose cisplatin, UFT, diethylstilbestrol diphosphate, and dexamethasone in a patient with hormonerefractory prostate cancer. Author(s): Hoshi S, Ohyama C, Hagisawa S, Ono K, Satoh M, Saito S, Fukuzaki A, Arai Y. Source: International Journal of Clinical Oncology / Japan Society of Clinical Oncology. 2003 April; 8(2): 118-20. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12720106&dopt=Abstract
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Complex patterns of regulation of chemokine secretion by Th2-cytokines, dexamethasone, and PGE2 in tuberculous osteomyelitis. Author(s): Wright KM, Friedland JS. Source: Journal of Clinical Immunology. 2003 May; 23(3): 184-93. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12797540&dopt=Abstract
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Concentration-dependent effects of mometasone furoate and dexamethasone on foetal lung fibroblast functions involved in airway inflammation and remodeling. Author(s): Sabatini F, Silvestri M, Sale R, Serpero L, Giuliani M, Scarso L, Favini P, Rossi GA. Source: Pulmonary Pharmacology & Therapeutics. 2003; 16(5): 287-97. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12877820&dopt=Abstract
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Consolidation therapy of multiple myeloma with thalidomide-dexamethasone after intensive chemotherapy. Author(s): Alexanian R, Weber D, Giralt S, Delasalle K. Source: Annals of Oncology : Official Journal of the European Society for Medical Oncology / Esmo. 2002 July; 13(7): 1116-9. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12176792&dopt=Abstract
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Controlled trial of dexamethasone in neonatal chronic lung disease: an 8-year followup of cardiopulmonary function and growth. Author(s): Mieskonen S, Eronen M, Malmberg LP, Turpeinen M, Kari MA, Hallman M. Source: Acta Paediatrica (Oslo, Norway : 1992). 2003 August; 92(8): 896-904. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12948063&dopt=Abstract
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Controlled trial of early dexamethasone treatment for the prevention of chronic lung disease in preterm infants: a 3-year follow-up. Author(s): Romagnoli C, Zecca E, Luciano R, Torrioli G, Tortorolo G. Source: Pediatrics. 2002 June; 109(6): E85. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12042579&dopt=Abstract
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Corticosteroids and fetal vasculature: effects of hydrocortisone, dexamethasone and betamethasone on human umbilical artery. Author(s): Potter SM, Dennedy MC, Morrison JJ. Source: Bjog : an International Journal of Obstetrics and Gynaecology. 2002 October; 109(10): 1126-31. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12387465&dopt=Abstract
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CXCR4 expression on monocytes is up-regulated by dexamethasone and is modulated by autologous CD3+ T cells. Author(s): Caulfield J, Fernandez M, Snetkov V, Lee T, Hawrylowicz C. Source: Immunology. 2002 February; 105(2): 155-62. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11872090&dopt=Abstract
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Cytoplasmic micro heavy chain confers sensitivity to dexamethasone-induced apoptosis in early B-lineage acute lymphoblastic leukemia. Author(s): Kim JM, Fang J, Rheingold S, Aplenc R, Wasserman R, Grupp SA. Source: Cancer Research. 2002 August 1; 62(15): 4212-6. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12154021&dopt=Abstract
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Deep-vein thrombosis in patients with multiple myeloma receiving first-line thalidomide-dexamethasone therapy. Author(s): Cavo M, Zamagni E, Cellini C, Tosi P, Cangini D, Cini M, Valdre L, Palareti G, Masini L, Tura S, Baccarani M. Source: Blood. 2002 September 15; 100(6): 2272-3. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12229885&dopt=Abstract
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Delivery of pharmacologically active dexamethasone into activated endothelial cells by dexamethasone-anti-E-selectin immunoconjugate. Author(s): Asgeirsdottir SA, Kok RJ, Everts M, Meijer DK, Molema G. Source: Biochemical Pharmacology. 2003 May 15; 65(10): 1729-39. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12754109&dopt=Abstract
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Determination of dexamethasone in urine by gas chromatography with negative chemical ionization mass spectrometry. Author(s): Huetos Hidalgo O, Jimenez Lopez M, Ajenjo Carazo E, San Andres Larrea M, Reuvers TB. Source: Journal of Chromatography. B, Analytical Technologies in the Biomedical and Life Sciences. 2003 May 5; 788(1): 137-46. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12668079&dopt=Abstract
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Dexamethasone 8 mg in combination with ondansetron 4 mg appears to be the optimal dose for the prevention of nausea and vomiting after laparoscopic cholecystectomy. Author(s): Elhakim M, Nafie M, Mahmoud K, Atef A. Source: Canadian Journal of Anaesthesia = Journal Canadien D'anesthesie. 2002 November; 49(9): 922-6. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12419717&dopt=Abstract
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Dexamethasone accelerates catabolism of leukotriene C4 in bronchial epithelial cells. Author(s): Zaitsu M, Hamasaki Y, Tsuji K, Matsuo M, Fujita I, Aoki Y, Ishii E, Kohashi O. Source: The European Respiratory Journal : Official Journal of the European Society for Clinical Respiratory Physiology. 2003 July; 22(1): 35-42. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12882448&dopt=Abstract
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Dexamethasone and adrenocorticotropin suppress prolactin secretion in humans. Author(s): Hubina E, Nagy GM, Toth BE, Ivan G, Gorombey Z, Szabolcs I, Kovacs L, Goth MI. Source: Endocrine. 2002 August; 18(3): 215-9. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12450312&dopt=Abstract
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Dexamethasone and retinoic acid differentially regulate growth and differentiation in an immortalised human clonal bone marrow stromal cell line with osteoblastic characteristics. Author(s): Ogston N, Harrison AJ, Cheung HF, Ashton BA, Hampson G. Source: Steroids. 2002 October; 67(11): 895-906. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12234625&dopt=Abstract
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Dexamethasone and tumor necrosis factor-alpha act together to induce the cellular inhibitor of apoptosis-2 gene and prevent apoptosis in a variety of cell types. Author(s): Webster JC, Huber RM, Hanson RL, Collier PM, Haws TF, Mills JK, Burn TC, Allegretto EA. Source: Endocrinology. 2002 October; 143(10): 3866-74. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12239098&dopt=Abstract
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Dexamethasone attenuates oxidation of extracellular matrix proteins by human monocytes. Author(s): Ahmed S, Adamidis A, Jan LC, Gibbons N, Mattana J. Source: Experimental and Molecular Pathology. 2003 October; 75(2): 137-43. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=14516775&dopt=Abstract
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Dexamethasone causes sustained expression of mitogen-activated protein kinase (MAPK) phosphatase 1 and phosphatase-mediated inhibition of MAPK p38. Author(s): Lasa M, Abraham SM, Boucheron C, Saklatvala J, Clark AR. Source: Molecular and Cellular Biology. 2002 November; 22(22): 7802-11. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12391149&dopt=Abstract
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Dexamethasone compared with betamethasone for glucocorticoid treatment of postpartum HELLP syndrome. Author(s): Isler CM, Magann EF, Rinehart BK, Terrone DA, Bass JD, Martin JN Jr. Source: International Journal of Gynaecology and Obstetrics: the Official Organ of the International Federation of Gynaecology and Obstetrics. 2003 March; 80(3): 291-7. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12628531&dopt=Abstract
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Dexamethasone decreases phospholipase C beta1 isozyme expression in human vascular smooth muscle cells. Author(s): Cueille C, Frayon S, de Vernejoul MC, Garel JM. Source: The Journal of Steroid Biochemistry and Molecular Biology. 2003 August; 86(2): 173-8. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=14568569&dopt=Abstract
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Dexamethasone does not exert direct intracellular feedback on steroidogenesis in human adrenal NCI-H295A cells. Author(s): Dardis A, Miller WL. Source: The Journal of Endocrinology. 2003 October; 179(1): 131-42. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=14529573&dopt=Abstract
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Dexamethasone enhances osteoclast formation synergistically with transforming growth factor-beta by stimulating the priming of osteoclast progenitors for differentiation into osteoclasts. Author(s): Takuma A, Kaneda T, Sato T, Ninomiya S, Kumegawa M, Hakeda Y. Source: The Journal of Biological Chemistry. 2003 November 7; 278(45): 44667-74. Epub 2003 August 27. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12944401&dopt=Abstract
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Dexamethasone enhances the effect of tropisetron and ondansetron against nausea and vomiting against nausea and vomiting after patient-controlled analgesia. Author(s): Wang C, Xu N, Xiong LZ, Liu HF, Yang XY, Lu ZH, Sheng PT, Wang LY. Source: Di Yi June Yi Da Xue Xue Bao. 2002 February; 22(2): 159-61. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12390816&dopt=Abstract
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Dexamethasone for morbidity after subdural electrode insertion--a randomized controlled trial. Author(s): Sahjpaul RL, Mahon J, Wiebe S. Source: The Canadian Journal of Neurological Sciences. Le Journal Canadien Des Sciences Neurologiques. 2003 November; 30(4): 340-8. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=14672266&dopt=Abstract
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Dexamethasone for treatment of patients mechanically ventilated for lower respiratory tract infection caused by respiratory syncytial virus. Author(s): van Woensel JB, van Aalderen WM, de Weerd W, Jansen NJ, van Gestel JP, Markhorst DG, van Vught AJ, Bos AP, Kimpen JL. Source: Thorax. 2003 May; 58(5): 383-7. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12728156&dopt=Abstract
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Dexamethasone in acute bacterial meningitis. Author(s): Principi N, Esposito S. Source: Lancet. 2002 November 16; 360(9345): 1610; Author Reply 1610-1. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12443642&dopt=Abstract
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Dexamethasone in acute bacterial meningitis. Author(s): Obaro SK. Source: Lancet. 2002 November 16; 360(9345): 1609-10; Author Reply 1610-1. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12443641&dopt=Abstract
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Dexamethasone in adults with bacterial meningitis. Author(s): Joffe AR. Source: The New England Journal of Medicine. 2003 March 6; 348(10): 954-7; Author Reply 954-7. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12622128&dopt=Abstract
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Dexamethasone in adults with bacterial meningitis. Author(s): Poshkus M, Obaro S. Source: The New England Journal of Medicine. 2003 March 6; 348(10): 954-7; Author Reply 954-7. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12622127&dopt=Abstract
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Dexamethasone in adults with bacterial meningitis. Author(s): Abril V, Ortega E. Source: The New England Journal of Medicine. 2003 March 6; 348(10): 954-7; Author Reply 954-7. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12622126&dopt=Abstract
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Dexamethasone in adults with bacterial meningitis. Author(s): Tancredi DN, Binder WD. Source: The New England Journal of Medicine. 2003 March 6; 348(10): 954-7; Author Reply 954-7. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12622125&dopt=Abstract
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Dexamethasone in adults with bacterial meningitis. Author(s): Tabas JA, Chambers HF. Source: The New England Journal of Medicine. 2003 March 6; 348(10): 954-7; Author Reply 954-7. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12621141&dopt=Abstract
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Dexamethasone in adults with bacterial meningitis. Author(s): de Gans J, van de Beek D; European Dexamethasone in Adulthood Bacterial Meningitis Study Investigators. Source: The New England Journal of Medicine. 2002 November 14; 347(20): 1549-56. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12432041&dopt=Abstract
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Dexamethasone in combination with dolasetron for prophylaxis in the ambulatory setting: effect on outcome after laparoscopic cholecystectomy. Author(s): Coloma M, White PF, Markowitz SD, Whitten CW, Macaluso AR, Berrisford SB, Thornton KC. Source: Anesthesiology. 2002 June; 96(6): 1346-50. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12170046&dopt=Abstract
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Dexamethasone induces rapid serine-phosphorylation and membrane translocation of annexin 1 in a human folliculostellate cell line via a novel nongenomic mechanism involving the glucocorticoid receptor, protein kinase C, phosphatidylinositol 3kinase, and mitogen-activated protein kinase. Author(s): Solito E, Mulla A, Morris JF, Christian HC, Flower RJ, Buckingham JC. Source: Endocrinology. 2003 April; 144(4): 1164-74. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12639897&dopt=Abstract
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Dexamethasone induces the secretion of annexin I in immature lymphoblastic cells by a calcium-dependent mechanism. Author(s): Castro-Caldas M, Duarte CB, Carvalho AP, Lopes MC. Source: Molecular and Cellular Biochemistry. 2002 August; 237(1-2): 31-8. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12236584&dopt=Abstract
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Dexamethasone induction of hypertension and diabetes is PPAR-alpha dependent in LDL receptor-null mice. Author(s): Bernal-Mizrachi C, Weng S, Feng C, Finck BN, Knutsen RH, Leone TC, Coleman T, Mecham RP, Kelly DP, Semenkovich CF. Source: Nature Medicine. 2003 August; 9(8): 1069-75. Epub 2003 July 06. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12847522&dopt=Abstract
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Dexamethasone inhibits apoptosis of human neutrophils induced by reactive oxygen species. Author(s): Ruiz LM, Bedoya G, Salazar J, Garcia de O D, Patino PJ. Source: Inflammation. 2002 October; 26(5): 215-22. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12238564&dopt=Abstract
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Dexamethasone inhibits TNF-alpha synthesis more effectively in Alzheimer's disease patients than in healthy individuals. Author(s): Dziedzic T, Wybranska I, Dembinska-Kiec A, Klimkowicz A, Slowik A, Pankiewicz J, Zdzienicka A, Szczudlik A. Source: Dementia and Geriatric Cognitive Disorders. 2003; 16(4): 283-6. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=14512725&dopt=Abstract
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Dexamethasone is as effective as ondansetron for the prevention of postoperative nausea and vomiting following breast surgery. Author(s): Wattwil M, Thorn SE, Lovqvist A, Wattwil L, Gupta A, Liljegren G. Source: Acta Anaesthesiologica Scandinavica. 2003 August; 47(7): 823-7. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12859302&dopt=Abstract
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Dexamethasone prevents interleukin-1beta-induced nuclear factor-kappaB activation by upregulating IkappaB-alpha synthesis, in lymphoblastic cells. Author(s): Castro-Caldas M, Mendes AF, Carvalho AP, Duarte CB, Lopes MC. Source: Mediators of Inflammation. 2003 February; 12(1): 37-46. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12745547&dopt=Abstract
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Dexamethasone prevents postoperative nausea and vomiting more effectively in women with motion sickness. Author(s): Lee Y, Lai HY, Lin PC, Huang SJ, Lin YS. Source: Canadian Journal of Anaesthesia = Journal Canadien D'anesthesie. 2003 March; 50(3): 232-7. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12620944&dopt=Abstract
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Dexamethasone pulse steroids in ulcerative colitis--is it time for a change? Author(s): Patel SM, Falchuk K. Source: Inflammatory Bowel Diseases. 2003 May; 9(3): 213. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12797351&dopt=Abstract
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Dexamethasone pulse therapy in pemphigus. Author(s): Toth GG, van de Meer JB, Jonkman MF. Source: Journal of the European Academy of Dermatology and Venereology : Jeadv. 2002 November; 16(6): 607-11. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12482045&dopt=Abstract
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Dexamethasone reduces pain after tonsillectomy in adults. Author(s): Stewart R, Bill R, Ullah R, McConaghy P, Hall SJ. Source: Clinical Otolaryngology and Allied Sciences. 2002 October; 27(5): 321-6. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12383289&dopt=Abstract
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Dexamethasone reduces postoperative troponin levels in children undergoing cardiopulmonary bypass. Author(s): Checchia PA, Backer CL, Bronicki RA, Baden HP, Crawford SE, Green TP, Mavroudis C. Source: Critical Care Medicine. 2003 June; 31(6): 1742-5. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12794414&dopt=Abstract
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Dexamethasone reduces postoperative vomiting and pain after pediatric tonsillectomy. Author(s): Elhakim M, Ali NM, Rashed I, Riad MK, Refat M. Source: Canadian Journal of Anaesthesia = Journal Canadien D'anesthesie. 2003 April; 50(4): 392-7. English, French. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12670818&dopt=Abstract
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Dexamethasone regulates endothelin-1 and endothelin receptors in human nonpigmented ciliary epithelial (HNPE) cells. Author(s): Zhang X, Krishnamoorthy RR, Prasanna G, Narayan S, Clark A, Yorio T. Source: Experimental Eye Research. 2003 March; 76(3): 261-72. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12573655&dopt=Abstract
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Dexamethasone suppresses peripheral prostanoid levels without analgesia in a clinical model of acute inflammation. Author(s): Dionne RA, Gordon SM, Rowan J, Kent A, Brahim JS. Source: Journal of Oral and Maxillofacial Surgery : Official Journal of the American Association of Oral and Maxillofacial Surgeons. 2003 September; 61(9): 997-1003. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12966473&dopt=Abstract
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Dexamethasone suppression test findings in subjects with personality disorders: associations with posttraumatic stress disorder and major depression. Author(s): Grossman R, Yehuda R, New A, Schmeidler J, Silverman J, Mitropoulou V, Sta Maria N, Golier J, Siever L. Source: The American Journal of Psychiatry. 2003 July; 160(7): 1291-8. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12832244&dopt=Abstract
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Dexamethasone treatment does not inhibit fibroproliferation in chronic lung disease of prematurity. Author(s): Dik WA, Versnel MA, Naber BA, Janssen DJ, van Kaam AH, Zimmermann LJ. Source: The European Respiratory Journal : Official Journal of the European Society for Clinical Respiratory Physiology. 2003 May; 21(5): 842-7. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12765431&dopt=Abstract
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Dexamethasone upregulates 11beta-hydroxysteroid dehydrogenase type 2 in BEAS-2B cells. Author(s): Suzuki S, Koyama K, Darnel A, Ishibashi H, Kobayashi S, Kubo H, Suzuki T, Sasano H, Krozowski ZS. Source: American Journal of Respiratory and Critical Care Medicine. 2003 May 1; 167(9): 1244-9. Epub 2003 February 05. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12574078&dopt=Abstract
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Dexamethasone versus prednisone and daily oral versus weekly intravenous mercaptopurine for patients with standard-risk acute lymphoblastic leukemia: a report from the Children's Cancer Group. Author(s): Bostrom BC, Sensel MR, Sather HN, Gaynon PS, La MK, Johnston K, Erdmann GR, Gold S, Heerema NA, Hutchinson RJ, Provisor AJ, Trigg ME; Children's Cancer Group. Source: Blood. 2003 May 15; 101(10): 3809-17. Epub 2003 January 16. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12531809&dopt=Abstract
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Dexamethasone/phenytoin interactions: neurooncological concerns. Author(s): Ruegg S. Source: Swiss Medical Weekly : Official Journal of the Swiss Society of Infectious Diseases, the Swiss Society of Internal Medicine, the Swiss Society of Pneumology. 2002 July 27; 132(29-30): 425-6. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12428189&dopt=Abstract
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Dexamethasone-associated toxicity during induction chemotherapy for childhood acute lymphoblastic leukemia is augmented by concurrent use of daunomycin. Author(s): Belgaumi AF, Al-Bakrah M, Al-Mahr M, Al-Jefri A, Al-Musa A, Saleh M, Salim MF, Osman M, Osman L, El-Solh H. Source: Cancer. 2003 June 1; 97(11): 2898-903. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12767105&dopt=Abstract
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Dexamethasone-induced effects on lymphocyte distribution and expression of adhesion molecules in treatment-resistant depression. Author(s): Bauer ME, Papadopoulos A, Poon L, Perks P, Lightman SL, Checkley S, Shanks N. Source: Psychiatry Research. 2002 December 15; 113(1-2): 1-15. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12467941&dopt=Abstract
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Dexamethasone-resistant human Pre-B leukemia 697 cell line evolving elevation of intracellular glutathione level: an additional resistance mechanism. Author(s): Inoue H, Takemura H, Kawai Y, Yoshida A, Ueda T, Miyashita T. Source: Japanese Journal of Cancer Research : Gann. 2002 May; 93(5): 582-90. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12036455&dopt=Abstract
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Differential effect of dexamethasone on cell death and STAT5 activation during in vitro eosinopoiesis. Author(s): Debierre-Grockiego F, Fuentes V, Prin L, Gouilleux F, Gouilleux-Gruart V. Source: British Journal of Haematology. 2003 December; 123(5): 933-41. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=14632786&dopt=Abstract
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Differential regulation of human CYP4A genes by peroxisome proliferators and dexamethasone. Author(s): Savas U, Hsu MH, Johnson EF. Source: Archives of Biochemistry and Biophysics. 2003 January 1; 409(1): 212-20. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12464261&dopt=Abstract
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Direct application of dexamethasone for the treatment of chronic eustachian tube dysfunction. Author(s): Silverstein H, Light JP, Jackson LE, Rosenberg SI, Thompson JH Jr. Source: Ear, Nose, & Throat Journal. 2003 January; 82(1): 28-32. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12610900&dopt=Abstract
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Discriminatory value of the low-dose dexamethasone suppression test in establishing the diagnosis and differential diagnosis of Cushing's syndrome. Author(s): Isidori AM, Kaltsas GA, Mohammed S, Morris DG, Jenkins P, Chew SL, Monson JP, Besser GM, Grossman AB. Source: The Journal of Clinical Endocrinology and Metabolism. 2003 November; 88(11): 5299-306. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=14602765&dopt=Abstract
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Distinct actions of prednisolone and dexamethasone towards osteocalcin and eosinophilic cationic protein in assumed clinically equivalent doses: a study in healthy men. Author(s): Dubois EF, Derks MG, Zwinderman AH, Dekhuijzen PN, Van Boxtel CJ, Schweitzer DH. Source: European Journal of Clinical Pharmacology. 2003 March; 58(11): 733-7. Epub 2003 February 15. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12634979&dopt=Abstract
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Does dexamethasone affect ceftriazone penetration into cerebrospinal fluid in adult bacterial meningitis. Author(s): Buke AC, Cavusoglu C, Karasulu E, Karakartal G. Source: International Journal of Antimicrobial Agents. 2003 May; 21(5): 452-6. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12727079&dopt=Abstract
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Does dexamethasone improve blood pressure in hypotensive ill neonates? Author(s): Nicholl R. Source: Archives of Disease in Childhood. 2001 September; 85(3): 253-4. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12035814&dopt=Abstract
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Double blind, randomized, placebo-controlled study of dexamethasone therapy for hematogenous septic arthritis in children. Author(s): Odio CM, Ramirez T, Arias G, Abdelnour A, Hidalgo I, Herrera ML, Bolanos W, Alpizar J, Alvarez P. Source: The Pediatric Infectious Disease Journal. 2003 October; 22(10): 883-8. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=14551489&dopt=Abstract
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Early dexamethasone decreases expression of activation markers on neutrophils and monocytes in preterm infants. Author(s): Nupponen I, Repo H, Kari A, Pohjavuori M, Andersson S. Source: Acta Paediatrica (Oslo, Norway : 1992). 2002; 91(11): 1200-7. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12463319&dopt=Abstract
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Early postnatal dexamethasone and cerebral palsy. Author(s): Halliday HL. Source: Pediatrics. 2002 June; 109(6): 1168-9. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12042559&dopt=Abstract
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Early postnatal dexamethasone decreases hepatocyte growth factor in tracheal aspirate fluid from premature infants. Author(s): Lassus P, Nupponen I, Kari A, Pohjavuori M, Andersson S. Source: Pediatrics. 2002 October; 110(4): 768-71. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12359793&dopt=Abstract
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Effect of a fourth Haemophilus influenzae type b immunisation in preterm infants who received dexamethasone for chronic lung disease. Author(s): Clarke P, Powell PJ, Goldblatt D, Robinson MJ. Source: Archives of Disease in Childhood. Fetal and Neonatal Edition. 2003 January; 88(1): F58-61. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12496229&dopt=Abstract
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Effect of celecoxib and dexamethasone on postoperative pain after lumbar disc surgery. Author(s): Karst M, Kegel T, Lukas A, Ludemann W, Hussein S, Piepenbrock S. Source: Neurosurgery. 2003 August; 53(2): 331-6; Discussion 336-7. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12925248&dopt=Abstract
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Effect of dexamethasone on beta2-adrenergic desensitization in airway smooth muscle: role of the ARG19 polymorphism. Author(s): Moore PE, Calder MM, Silverman ES, Panettieri RA Jr, Shore SA. Source: Chest. 2003 March; 123(3 Suppl): 368S-9S. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12628978&dopt=Abstract
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Effect of dexamethasone on cultured human tenocytes and its reversibility by platelet-derived growth factor. Author(s): Wong MW, Tang YY, Lee SK, Fu BS, Chan BP, Chan CK. Source: The Journal of Bone and Joint Surgery. American Volume. 2003 October; 85A(10): 1914-20. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=14563798&dopt=Abstract
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Effect of dexamethasone on growth inhibition and chondrogenic maturation of human chondrosarcoma. Author(s): Kawashima H, Ogose A, Hayami T, Yamagiwa H, Hatano H, Hotta T, Endo N. Source: Journal of Orthopaedic Science : Official Journal of the Japanese Orthopaedic Association. 2003; 8(3): 341-5. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12768476&dopt=Abstract
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Effect of dexamethasone on tracheal viral load and interleukin-8 tracheal concentration in children with respiratory syncytial virus infection. Author(s): van Woensel JB, Lutter R, Biezeveld MH, Dekker T, Nijhuis M, van Aalderen WM, Kuijpers TW. Source: The Pediatric Infectious Disease Journal. 2003 August; 22(8): 721-6. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12913774&dopt=Abstract
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Effect of dexamethasone treatment on serum GH, IGF-I, and the binding proteins IGFBP-1 and -3 in ventilated very preterm infants. Author(s): Huysman MW, Hokken-Koelega AC, Hop WC, Sauer PJ. Source: Pediatric Research. 2003 July; 54(1): 37-43. Epub 2003 March 19. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12646720&dopt=Abstract
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Effect of small doses of dexamethasone on plasma leptin levels in normal and obese subjects: a dose-response study. Author(s): Putignano P, Brunani A, Dubini A, Bertolini M, Pasquali R, Cavagnini F; “Study Group on Obesity” of the Italian Society of Endocrinology. Source: J Endocrinol Invest. 2003 February; 26(2): 111-6. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12739736&dopt=Abstract
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Effects of carbamazepine on dexamethasone suppression and sleep electroencephalography in borderline personality disorder. Author(s): De la Fuente JM, Bobes J, Vizuete C, Mendlewicz J. Source: Neuropsychobiology. 2002; 45(3): 113-9. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11979058&dopt=Abstract
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Effects of dexamethasone and sex hormones on cytokine-induced cellular adhesion molecule expression in human endothelial cells. Author(s): Chen W, Lee JY, Hsieh WC. Source: European Journal of Dermatology : Ejd. 2002 September-October; 12(5): 445-8. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12370131&dopt=Abstract
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Effects of dexamethasone on aryl (SULT1A1)- and hydroxysteroid (SULT2A1)sulfotransferase gene expression in primary cultured human hepatocytes. Author(s): Duanmu Z, Locke D, Smigelski J, Wu W, Dahn MS, Falany CN, Kocarek TA, Runge-Morris M. Source: Drug Metabolism and Disposition: the Biological Fate of Chemicals. 2002 September; 30(9): 997-1004. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12167565&dopt=Abstract
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Effects of dexamethasone on clinical course, C-reactive protein, S100B protein and von Willebrand factor antigen after paediatric cardiac surgery. Author(s): Lindberg L, Forsell C, Jogi P, Olsson AK. Source: British Journal of Anaesthesia. 2003 June; 90(6): 728-32. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12765886&dopt=Abstract
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Effects of Dexamethasone on glucocorticoid receptor expression in a human ovarian carcinoma cell line 3AO. Author(s): Xu M, Song L, Wang Z. Source: Chinese Medical Journal. 2003 March; 116(3): 392-5. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12781044&dopt=Abstract
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Effects of dexamethasone on intravascular and extravascular fluid balance in patients undergoing coronary bypass surgery with cardiopulmonary bypass. Author(s): von Spiegel T, Giannaris S, Wietasch GJ, Schroeder S, Buhre W, Schorn B, Hoeft A. Source: Anesthesiology. 2002 April; 96(4): 827-34. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11964588&dopt=Abstract
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Effects of dexamethasone on mucin gene expression in cultured human nasal epithelial cells. Author(s): Ishinaga H, Takeuchi K, Kishioka C, Yagawa M, Majima Y. Source: The Laryngoscope. 2002 August; 112(8 Pt 1): 1436-40. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12172258&dopt=Abstract
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Effects of dexamethasone on proliferation of and fibronectin synthesis by human primary prostatic stromal cells in vitro. Author(s): Albrecht M, Janssen M, Konrad L, Renneberg H, Aumuller G. Source: Andrologia. 2002 February; 34(1): 11-21. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11996177&dopt=Abstract
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Effects of dexamethasone on proliferation, differentiation and apoptosis of adult human osteoblasts in vitro. Author(s): Yang L, Tao T, Wang X, Du N, Chen W, Tao S, Wang Z, Wu L. Source: Chinese Medical Journal. 2003 September; 116(9): 1357-60. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=14527365&dopt=Abstract
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Effects of dexamethasone on proteoglycan content and gene expression of IL-1betastimulated osteoarthrotic chondrocytes in vitro. Author(s): Stove J, Schoniger R, Huch K, Brenner R, Gunther KP, Puhl W, Scharf HP. Source: Acta Orthopaedica Scandinavica. 2002 October; 73(5): 562-7. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12440501&dopt=Abstract
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Effects of dexamethasone on the metabolic responses to mental stress in humans. Author(s): Seematter G, Battilana P, Tappy L. Source: Clinical Physiology and Functional Imaging. 2002 March; 22(2): 139-44. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12005156&dopt=Abstract
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Effects of dexamethasone, diclofenac, or placebo on the inflammatory response after cataract surgery. Author(s): Laurell CG, Zetterstrom C. Source: The British Journal of Ophthalmology. 2002 December; 86(12): 1380-4. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12446370&dopt=Abstract
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Effects of early dexamethasone therapy on pulmonary fibrogenic mediators and respiratory mechanics in preterm infants. Author(s): Vento G, Matassa PG, Ameglio F, Capoluongo E, Tortorolo L, Romagnoli C. Source: European Cytokine Network. 2002 April-June; 13(2): 207-14. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12101076&dopt=Abstract
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Effects of iontophoresis current magnitude and duration on dexamethasone deposition and localized drug retention. Author(s): Anderson CR, Morris RL, Boeh SD, Panus PC, Sembrowich WL. Source: Physical Therapy. 2003 February; 83(2): 161-70. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12564951&dopt=Abstract
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Effects of short-term dexamethasone treatment on collagen synthesis and degradation markers in preterm infants with developing lung disease. Author(s): Saarela T, Risteli J, Koivisto M. Source: Acta Paediatrica (Oslo, Norway : 1992). 2003 May; 92(5): 588-94. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12839290&dopt=Abstract
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Effects of the neurokinin1 receptor antagonist aprepitant on the pharmacokinetics of dexamethasone and methylprednisolone. Author(s): McCrea JB, Majumdar AK, Goldberg MR, Iwamoto M, Gargano C, Panebianco DL, Hesney M, Lines CR, Petty KJ, Deutsch PJ, Murphy MG, Gottesdiener KM, Goldwater DR, Blum RA. Source: Clinical Pharmacology and Therapeutics. 2003 July; 74(1): 17-24. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12844131&dopt=Abstract
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Efficacy of albendazole and short-course dexamethasone treatment in children with 1 or 2 ring-enhancing lesions of neurocysticercosis: a randomized controlled trial. Author(s): Kalra V, Dua T, Kumar V. Source: The Journal of Pediatrics. 2003 July; 143(1): 111-4. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12915835&dopt=Abstract
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Equivalent mobilization and collection of granulocytes for transfusion after administration of glycosylated G-CSF (3 microg/kg) plus dexamethasone versus glycosylated G-CSF (12 microg/kg) alone. Author(s): Heuft HG, Goudeva L, Sel S, Blasczyk R. Source: Transfusion. 2002 July; 42(7): 928-34. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12375667&dopt=Abstract
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Evaluation of dexamethasone suppression test in fibromyalgia patients with or without depression. Author(s): Ataoglu S, Ozcetin A, Yildiz O, Ataoglu A. Source: Swiss Medical Weekly : Official Journal of the Swiss Society of Infectious Diseases, the Swiss Society of Internal Medicine, the Swiss Society of Pneumology. 2003 April 19; 133(15-16): 241-4. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12811674&dopt=Abstract
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Evidence for post-transcriptional regulation of interleukin-5 by dexamethasone. Author(s): Staples KJ, Bergmann MW, Barnes PJ, Newton R. Source: Immunology. 2003 August; 109(4): 527-35. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12871219&dopt=Abstract
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Ex vivo stimulation of renal transport of the cytostatic drugs methotrexate, cisplatin, topotecan (Hycamtin) and raltitrexed (Tomudex) by dexamethasone, T3 and EGF in intact human and rat kidney tissue and in human renal cell carcinoma. Author(s): Fleck C, Hilger R, Jurkutat S, Karge E, Merkel U, Schimske A, Schubert J. Source: Urological Research. 2002 September; 30(4): 256-62. Epub 2002 June 22. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12202944&dopt=Abstract
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Excruciating perineal pain after intravenous dexamethasone. Author(s): Neff SP, Stapelberg E, Warmington A. Source: Anaesthesia and Intensive Care. 2002 June; 30(3): 370-1. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12075649&dopt=Abstract
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Extension of replicative lifespan in WI-38 human fibroblasts by dexamethasone treatment is accompanied by suppression of p21 Waf1/Cip1/Sdi1 levels. Author(s): Mawal-Dewan M, Frisoni L, Cristofalo VJ, Sell C. Source: Experimental Cell Research. 2003 April 15; 285(1): 91-8. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12681289&dopt=Abstract
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Failure to detect dexamethasone phosphate in the local venous blood postcathodic lontophoresis in humans. Author(s): Smutok MA, Mayo MF, Gabaree CL, Ferslew KE, Panus PC. Source: The Journal of Orthopaedic and Sports Physical Therapy. 2002 September; 32(9): 461-8. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12322812&dopt=Abstract
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Falsely positive dexamethasone suppression test in a patient treated with phenytoin to prevent seizures due to nocardia brain abscesses. Author(s): Debrunner J, Schmid C, Schneemann M. Source: Swiss Medical Weekly : Official Journal of the Swiss Society of Infectious Diseases, the Swiss Society of Internal Medicine, the Swiss Society of Pneumology. 2002 May 18; 132(19-20): 267. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12148082&dopt=Abstract
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Fludarabine, ara-C, novantrone and dexamethasone (FAND) in previously treated chronic lymphocytic leukemia patients. Author(s): Mauro FR, Foa R, Meloni G, Gentile M, Giammartini E, Giannarelli D, De Propris MS, Rapanotti MC, de Fabritiis P, Mandelli F. Source: Haematologica. 2002 September; 87(9): 926-33. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12217804&dopt=Abstract
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Fludarabine, mitoxantrone, dexamethasone (FND) compared with an alternating triple therapy (ATT) regimen in patients with stage IV indolent lymphoma. Author(s): Tsimberidou AM, McLaughlin P, Younes A, Rodriguez MA, Hagemeister FB, Sarris A, Romaguera J, Hess M, Smith TL, Yang Y, Ayala A, Preti A, Lee MS, Cabanillas F. Source: Blood. 2002 December 15; 100(13): 4351-7. Epub 2002 August 08. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12393618&dopt=Abstract
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Follow up of a randomised trial of two different courses of dexamethasone for preterm babies at risk of chronic lung disease. Author(s): Armstrong DL, Penrice J, Bloomfield FH, Knight DB, Dezoete JA, Harding JE. Source: Archives of Disease in Childhood. Fetal and Neonatal Edition. 2002 March; 86(2): F102-7. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11882552&dopt=Abstract
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Fractionated cyclophosphamide, vincristine, liposomal daunorubicin, and dexamethasone plus rituximab and granulocyte-macrophage-colony stimulating factor (GM-CSF) alternating with methotrexate and cytarabine plus rituximab and GM-CSF in patients with Richter syndrome or fludarabine-refractory chronic lymphocytic leukemia. Author(s): Tsimberidou AM, Kantarjian HM, Cortes J, Thomas DA, Faderl S, GarciaManero G, Verstovsek S, Ferrajoli A, Wierda W, Alvarado Y, O'Brien SM, Albitar M, Keating MJ, Giles FJ. Source: Cancer. 2003 April 1; 97(7): 1711-20. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12655528&dopt=Abstract
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Gastric restitution is inhibited by dexamethasone, which is reversed by hepatocyte growth factor and rebamipide. Author(s): Takahashi M, Takada H, Takagi K, Kataoka S, Soma R, Kuwayama H. Source: Alimentary Pharmacology & Therapeutics. 2003 July; 18 Suppl 1: 126-32. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12925150&dopt=Abstract
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Granisetron plus dexamethasone versus granisetron alone in the prevention of vomiting induced by conditioning for stem cell transplantation: a prospective randomized study. Author(s): Matsuoka S, Okamoto S, Watanabe R, Mori T, Nagayama H, Hamano Y, Yokoyama K, Takayama N, Ikeda Y. Source: International Journal of Hematology. 2003 January; 77(1): 86-90. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12568305&dopt=Abstract
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Granisetron versus granisetron/dexamethasone combination for the treatment of nausea, retching, and vomiting after major gynecologic surgery: a randomized, double-blind study. Author(s): Fujii Y, Tanaka H. Source: Clinical Therapeutics. 2003 February; 25(2): 507-14. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12749510&dopt=Abstract
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HbF reactivation in sibling BFU-E colonies: synergistic interaction of kit ligand with low-dose dexamethasone. Author(s): Gabbianelli M, Testa U, Massa A, Morsilli O, Saulle E, Sposi NM, Petrucci E, Mariani G, Peschle C. Source: Blood. 2003 April 1; 101(7): 2826-32. Epub 2002 November 07. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12424200&dopt=Abstract
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Hematopoietic protection by dexamethasone or granulocyte-macrophage colonystimulating factor (GM-CSF) in patients treated with carboplatin and ifosfamide. Author(s): Rinehart J, Keville L, Neidhart J, Wong L, DiNunno L, Kinney P, Aberle M, Tadlock L, Cloud G. Source: American Journal of Clinical Oncology : the Official Publication of the American Radium Society. 2003 October; 26(5): 448-58. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=14528069&dopt=Abstract
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Hemopericardium and cardiac tamponade as presenting findings of dexamethasoneinduced hypertrophic cardiomyopathy complicated by transmural myocardial infarction. Author(s): Lilien LD, Lilien RH, Setrakian S. Source: Pediatric Cardiology. 2003 May-June; 24(3): 280-3. Epub 2003 March 14. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12632228&dopt=Abstract
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Hexokinase translocation during neutrophil activation, chemotaxis, and phagocytosis: disruption by cytochalasin D, dexamethasone, and indomethacin. Author(s): Huang JB, Kindzelskii AL, Petty HR. Source: Cellular Immunology. 2002 July-August; 218(1-2): 95-106. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12470617&dopt=Abstract
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High-dose dexamethasone as initial treatment for immune thrombocytopenic purpura. Author(s): Godeau B, Bierling P. Source: The New England Journal of Medicine. 2003 December 4; 349(23): 2267-8; Author Reply 2267-8. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=14657437&dopt=Abstract
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High-dose infusional ifosfamide, etoposide plus methylprednisolone followed by dexamethasone, high-dose ara-C and cisplatinum and autologous stem cell transplantation for refractory or relapsed aggressive non-Hodgkin's lymphoma. Author(s): Salar A, Martino R, Perea G, Ribera JM, Lopez-Guillermo A, Guardia R, Escoda L, Altes A, Sierra J, Montserrat E. Source: Haematologica. 2002 October; 87(10): 1028-35. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12368156&dopt=Abstract
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HPA hyperactivity with increased plasma cortisol affects dexamethasone metabolism and DST outcome. Author(s): Stokes PE, Sikes C, Lasley B, Stoll P. Source: Journal of Psychiatric Research. 2002 November-December; 36(6): 417-21. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12393311&dopt=Abstract
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Hsp27 inhibits release of mitochondrial protein Smac in multiple myeloma cells and confers dexamethasone resistance. Author(s): Chauhan D, Li G, Hideshima T, Podar K, Mitsiades C, Mitsiades N, Catley L, Tai YT, Hayashi T, Shringarpure R, Burger R, Munshi N, Ohtake Y, Saxena S, Anderson KC. Source: Blood. 2003 November 1; 102(9): 3379-86. Epub 2003 July 10. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12855565&dopt=Abstract
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Human SP-A 3'-UTR variants mediate differential gene expression in basal levels and in response to dexamethasone. Author(s): Wang G, Guo X, Floros J. Source: American Journal of Physiology. Lung Cellular and Molecular Physiology. 2003 May; 284(5): L738-48. Epub 2003 January 10. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12676764&dopt=Abstract
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Hyaluronan, a major non-protein glycosaminoglycan component of the extracellular matrix in human bone marrow, mediates dexamethasone resistance in multiple myeloma. Author(s): Vincent T, Molina L, Espert L, Mechti N. Source: British Journal of Haematology. 2003 April; 121(2): 259-69. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12694247&dopt=Abstract
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Hyperfractionated cyclophosphamide in combination with pulsed dexamethasone and thalidomide (HyperCDT) in primary refractory or relapsed multiple myeloma. Author(s): Kropff MH, Lang N, Bisping G, Domine N, Innig G, Hentrich M, Mitterer M, Sudhoff T, Fenk R, Straka C, Heinecke A, Koch OM, Ostermann H, Berdel WE, Kienast J. Source: British Journal of Haematology. 2003 August; 122(4): 607-16. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12899716&dopt=Abstract
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Hyperfractionated cyclophosphamide, vincristine, doxorubicin, and dexamethasone and highly active antiretroviral therapy for patients with acquired immunodeficiency syndrome-related Burkitt lymphoma/leukemia. Author(s): Cortes J, Thomas D, Rios A, Koller C, O'Brien S, Jeha S, Faderl S, Kantarjian H. Source: Cancer. 2002 March 1; 94(5): 1492-9. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11920506&dopt=Abstract
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Hyperresponsiveness of hypothalamic-pituitary-adrenal axis to combined dexamethasone/corticotropin-releasing hormone challenge in female borderline personality disorder subjects with a history of sustained childhood abuse. Author(s): Rinne T, de Kloet ER, Wouters L, Goekoop JG, DeRijk RH, van den Brink W. Source: Biological Psychiatry. 2002 December 1; 52(11): 1102-12. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12460693&dopt=Abstract
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Hypothalamo-pituitary-adrenal axis dysregulation in patients with rheumatoid arthritis after the dexamethasone/corticotrophin releasing factor test. Author(s): Harbuz MS, Korendowych E, Jessop DS, Crown AL, Li pdfan SL, Kirwan JR. Source: The Journal of Endocrinology. 2003 July; 178(1): 55-60. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12844336&dopt=Abstract
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Hypoxia and pulmonary acclimatisation at 4578 m altitude: the role of acetazolamide and dexamethasone. Author(s): Hussain MM, Aslam M. Source: J Pak Med Assoc. 2003 October; 53(10): 451-8. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=14696884&dopt=Abstract
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Identification of a functional link for the p53 tumor suppressor protein in dexamethasone-induced growth suppression. Author(s): Urban G, Golden T, Aragon IV, Cowsert L, Cooper SR, Dean NM, Honkanen RE. Source: The Journal of Biological Chemistry. 2003 March 14; 278(11): 9747-53. Epub 2003 January 07. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12519780&dopt=Abstract
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Identification of dexamethasone-dependent osteoprogenitors in cell populations derived from adult human female bone. Author(s): Pei W, Yoshimine Y, Heersche JN. Source: Calcified Tissue International. 2003 February; 72(2): 124-34. Epub 2002 November 06. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12415421&dopt=Abstract
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Identification of genes regulated by dexamethasone in multiple myeloma cells using oligonucleotide arrays. Author(s): Chauhan D, Auclair D, Robinson EK, Hideshima T, Li G, Podar K, Gupta D, Richardson P, Schlossman RL, Krett N, Chen LB, Munshi NC, Anderson KC. Source: Oncogene. 2002 February 21; 21(9): 1346-58. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11857078&dopt=Abstract
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IGF and IGF-binding protein expression in the growth plate of normal, dexamethasone-treated and human IGF-II transgenic mice. Author(s): Smink JJ, Koster JG, Gresnigt MG, Rooman R, Koedam JA, Van Buul-Offers SC. Source: The Journal of Endocrinology. 2002 October; 175(1): 143-53. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12379498&dopt=Abstract
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Immediate and delayed complications of dexamethasone cyclophosphamide pulse (DCP) therapy. Author(s): Jain R, Kumar B. Source: The Journal of Dermatology. 2003 October; 30(10): 713-8. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=14684952&dopt=Abstract
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Immediate and delayed effects of antenatal corticosteroids on fetal heart rate: a randomized trial that compares betamethasone acetate and phosphate, betamethasone phosphate, and dexamethasone. Author(s): Subtil D, Tiberghien P, Devos P, Therby D, Leclerc G, Vaast P, Puech F. Source: American Journal of Obstetrics and Gynecology. 2003 February; 188(2): 524-31. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12592266&dopt=Abstract
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Impaired inhibition by dexamethasone of cytokine release by alveolar macrophages from patients with chronic obstructive pulmonary disease. Author(s): Culpitt SV, Rogers DF, Shah P, De Matos C, Russell RE, Donnelly LE, Barnes PJ. Source: American Journal of Respiratory and Critical Care Medicine. 2003 January 1; 167(1): 24-31. Epub 2002 September 17. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12406856&dopt=Abstract
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Implementing potentially better practices to improve neonatal outcomes after reducing postnatal dexamethasone use in infants born between 501 and 1250 grams. Author(s): Kaempf JW, Campbell B, Sklar RS, Arduza C, Gallegos R, Zabari M, Brown A, McDonald JV. Source: Pediatrics. 2003 April; 111(4 Pt 2): E534-41. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12671173&dopt=Abstract
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In vitro human scleral permeability of fluorescein, dexamethasone-fluorescein, methotrexate-fluorescein and rhodamine 6G and the use of a coated coil as a new drug delivery system. Author(s): Cruysberg LP, Nuijts RM, Geroski DH, Koole LH, Hendrikse F, Edelhauser HF. Source: Journal of Ocular Pharmacology and Therapeutics : the Official Journal of the Association for Ocular Pharmacology and Therapeutics. 2002 December; 18(6): 559-69. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12537682&dopt=Abstract
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In vitro susceptibility to dexamethasone- and doxorubicin-induced apoptotic cell death in context of maturation stage, responsiveness to interleukin 7, and early cytoreduction in vivo in childhood T-cell acute lymphoblastic leukemia. Author(s): Wuchter C, Ruppert V, Schrappe M, Dorken B, Ludwig WD, Karawajew L. Source: Blood. 2002 June 1; 99(11): 4109-15. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12010814&dopt=Abstract
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Induction of the upstream regulatory region of human papillomavirus type 31 by dexamethasone is differentiation dependent. Author(s): Bromberg-White JL, Sen E, Alam S, Bodily JM, Meyers C. Source: Journal of Virology. 2003 October; 77(20): 10975-83. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=14512546&dopt=Abstract
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Inhibition by dexamethasone of interleukin 13 production via glucocorticoid receptor-mediated inhibition of c-Jun phosphorylation. Author(s): Hirasawa N, Izumi S, Linwong W, Ohuchi K. Source: Febs Letters. 2003 November 20; 554(3): 489-93. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=14623117&dopt=Abstract
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Inhibition of cytokine release from alveolar macrophages in pulmonary sarcoidosis by pentoxifylline: comparison with dexamethasone. Author(s): Tong Z, Dai H, Chen B, Abdoh Z, Guzman J, Costabel U. Source: Chest. 2003 October; 124(4): 1526-32. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=14555589&dopt=Abstract
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Inhibition of epidermal growth factor-induced invasion by dexamethasone and AP-1 decoy in human squamous cell carcinoma cell lines. Author(s): Shiratsuchi T, Ishibashi H, Shirasuna K. Source: Journal of Cellular Physiology. 2002 December; 193(3): 340-8. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12384986&dopt=Abstract
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Inhibition of immunoglobulin G-catalyzed hydrogen peroxide generation by dexamethasone and piroxicam. Author(s): Oyanagui Y, Taniguchi M, Iwata M, Murakami M. Source: Life Sciences. 2003 July 25; 73(10): 1333-46. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12850247&dopt=Abstract
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Initial treatment of immune thrombocytopenic purpura with high-dose dexamethasone. Author(s): Cheng Y, Wong RS, Soo YO, Chui CH, Lau FY, Chan NP, Wong WS, Cheng G. Source: The New England Journal of Medicine. 2003 August 28; 349(9): 831-6. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12944568&dopt=Abstract
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Inositol treatment has no effect on the dexamethasone suppression test. Author(s): Levine J, Leventhal U, Lerner V, Belmaker RH. Source: World J Biol Psychiatry. 2001 October; 2(4): 190-2. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12587148&dopt=Abstract
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Interactions of endothelin-1 with dexamethasone in primary cultured human trabecular meshwork cells. Author(s): Zhang X, Clark AF, Yorio T. Source: Investigative Ophthalmology & Visual Science. 2003 December; 44(12): 5301-8. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=14638730&dopt=Abstract
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Interleukin-4 and interleukin-13 augment the proliferative effect of dexamethasone on distal lung fibroblasts. Author(s): Lewis CC, Sutherland ER, Moss TA, Metze TL, Rex MD, Kraft M. Source: Chest. 2003 March; 123(3 Suppl): 356S. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12628974&dopt=Abstract
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Intermediate doses of melphalan and dexamethasone are better than vincristine, adriamycin, and dexamethasone (VAD) and polychemotherapy for the treatment of primary plasma cell leukemia. Author(s): Vela-Ojeda J, Garcia-Ruiz Esparza MA, Rosas-Cabral A, Padilla-Gonzalez Y, Garcia-Chavez J, Tripp-Villanueva F, Sanchez-Cortes E, Ayala-Sanchez M, Garcia-Leon LD, Montiel-Cervantes L, Rubio-Borja ME. Source: Annals of Hematology. 2002 July; 81(7): 362-7. Epub 2002 June 25. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12185504&dopt=Abstract
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Intramuscular versus oral dexamethasone for the treatment of moderate-to-severe croup: a randomized, double-blind trial. Author(s): Donaldson D, Poleski D, Knipple E, Filips K, Reetz L, Pascual RG, Jackson RE. Source: Academic Emergency Medicine : Official Journal of the Society for Academic Emergency Medicine. 2003 January; 10(1): 16-21. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12511310&dopt=Abstract
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Intraocular penetration and systemic absorption after topical application of dexamethasone disodium phosphate. Author(s): Weijtens O, Schoemaker RC, Romijn FP, Cohen AF, Lentjes EG, van Meurs JC. Source: Ophthalmology. 2002 October; 109(10): 1887-91. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12359610&dopt=Abstract
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Intravitreal dexamethasone effectively reduces postoperative inflammation after vitreoretinal surgery. Author(s): Chalam KV, Malkani S, Shah VA. Source: Ophthalmic Surgery, Lasers & Imaging : the Official Journal of the International Society for Imaging in the Eye. 2003 May-June; 34(3): 188-92. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12757090&dopt=Abstract
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Iontophoretic administration of dexamethasone sodium phosphate for acute epicondylitis. A randomized, double-blinded, placebo-controlled study. Author(s): Nirschl RP, Rodin DM, Ochiai DH, Maartmann-Moe C; DEX-AHE-01-99 Study Group. Source: The American Journal of Sports Medicine. 2003 March-April; 31(2): 189-95. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12642251&dopt=Abstract
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Is dexamethasone effective in treating acute migraine headache? Author(s): Wasiak J, Anderson JN. Source: The Medical Journal of Australia. 2002 January 21; 176(2): 83. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11936293&dopt=Abstract
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Kinetics of G-CSF-induced granulocyte mobilization in healthy subjects: effects of route of administration and addition of dexamethasone. Author(s): Stroncek DF, Matthews CL, Follmann D, Leitman SF. Source: Transfusion. 2002 May; 42(5): 597-602. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12084168&dopt=Abstract
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Liposomal daunorubicin (DaunoXome) plus dexamethasone for patients with multiple myeloma. A phase II International Oncology Study Group study. Author(s): Mohrbacher AF, Gregory SA, Gabriel DA, Rusk JM, Giles FJ. Source: Cancer. 2002 May 15; 94(10): 2645-52. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12173332&dopt=Abstract
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Lithium augmentation increases post-dexamethasone cortisol in the dexamethasone suppression test in unipolar major depression. Author(s): Bschor T, Baethge C, Adli M, Eichmann U, Ising M, Uhr M, MullerOerlinghausen B, Bauer M. Source: Depression and Anxiety. 2003; 17(1): 43-8. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12577277&dopt=Abstract
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Local methotrexate and dexamethasone phosphate for the treatment of recurrent primary intraocular lymphoma. Author(s): Velez G, Boldt HC, Whitcup SM, Nussenblatt RB, Robinson MR. Source: Ophthalmic Surgery and Lasers. 2002 July-August; 33(4): 329-33. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12134997&dopt=Abstract
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Long-term efficacy of dexamethasone-cyclophosphamide pulse therapy in pemphigus. Author(s): Kanwar AJ, Kaur S, Thami GP. Source: Dermatology (Basel, Switzerland). 2002; 204(3): 228-31. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12037452&dopt=Abstract
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Low dose latrunculin-A inhibits dexamethasone-induced changes in the actin cytoskeleton and alters extracellular matrix protein expression in cultured human trabecular meshwork cells. Author(s): Liu X, Wu Z, Sheibani N, Brandt CR, Polansky JR, Kaufman PL. Source: Experimental Eye Research. 2003 August; 77(2): 181-8. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12873448&dopt=Abstract
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Low-dose dexamethasone reduces nausea and vomiting after epidural morphine: a comparison of metoclopramide with saline. Author(s): Tzeng JI, Hsing CH, Chu CC, Chen YH, Wang JJ. Source: Journal of Clinical Anesthesia. 2002 February; 14(1): 19-23. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11880017&dopt=Abstract
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Low-dose dexamethasone reduces nausea and vomiting after tympanomastoid surgery: a comparison of tropisetron with saline. Author(s): Wang JJ, Wang PC, Liu YH, Chien CC. Source: American Journal of Otolaryngology. 2002 September-October; 23(5): 267-71. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12239690&dopt=Abstract
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Low-dose dexamethasone suppression test in chronic fatigue syndrome and health. Author(s): Gaab J, Huster D, Peisen R, Engert V, Schad T, Schurmeyer TH, Ehlert U. Source: Psychosomatic Medicine. 2002 March-April; 64(2): 311-8. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11914448&dopt=Abstract
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Metabolic adaptations to dexamethasone-induced insulin resistance in healthy volunteers. Author(s): Nicod N, Giusti V, Besse C, Tappy L. Source: Obesity Research. 2003 May; 11(5): 625-31. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12740452&dopt=Abstract
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Metronomic therapy with cyclophosphamide and dexamethasone for prostate carcinoma. Author(s): Glode LM, Barqawi A, Crighton F, Crawford ED, Kerbel R. Source: Cancer. 2003 October 15; 98(8): 1643-8. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=14534880&dopt=Abstract
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Modulation of cadherin and catenins expression by tumor necrosis factor-alpha and dexamethasone in human bronchial epithelial cells. Author(s): Carayol N, Campbell A, Vachier I, Mainprice B, Bousquet J, Godard P, Chanez P. Source: American Journal of Respiratory Cell and Molecular Biology. 2002 March; 26(3): 341-7. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11867342&dopt=Abstract
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Modulation of leukotriene B4 receptor-1 expression by dexamethasone: potential mechanism for enhanced neutrophil survival. Author(s): Stankova J, Turcotte S, Harris J, Rola-Pleszczynski M. Source: Journal of Immunology (Baltimore, Md. : 1950). 2002 April 1; 168(7): 3570-6. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11907121&dopt=Abstract
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Neonatologists are using much less dexamethasone. Author(s): Shinwell ES, Karplus M, Bader D, Dollberg S, Gur I, Weintraub Z, Arnon S, Gottfreid E, Zaritsky A, Makhoul IR, Reich D, Sirota L, Berger I, Kogan A, Yurman S, Goldberg M, Kohelet D. Source: Archives of Disease in Childhood. Fetal and Neonatal Edition. 2003 September; 88(5): F432-3. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12937052&dopt=Abstract
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Neopterin levels and dexamethasone suppression test in posttraumatic stress disorder. Author(s): Atmaca M, Kuloglu M, Tezcan E, Onal S, Ustundag B. Source: European Archives of Psychiatry and Clinical Neuroscience. 2002 August; 252(4): 161-5. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12242576&dopt=Abstract
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Neutrophil defensins stimulate the release of cytokines by airway epithelial cells: modulation by dexamethasone. Author(s): van Wetering S, Mannesse-Lazeroms SP, van Sterkenburg MA, Hiemstra PS. Source: Inflammation Research : Official Journal of the European Histamine Research Society. [et Al.]. 2002 January; 51(1): 8-15. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11852911&dopt=Abstract
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Ondansetron and dolasetron provide equivalent postoperative vomiting control after ambulatory tonsillectomy in dexamethasone-pretreated children. Author(s): Sukhani R, Pappas AL, Lurie J, Hotaling AJ, Park A, Fluder E. Source: Anesthesia and Analgesia. 2002 November; 95(5): 1230-5, Table of Contents. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12401599&dopt=Abstract
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Oral dexamethasone for the treatment of pain in children with acute pharyngitis: a randomized, double-blind, placebo-controlled trial. Author(s): Bulloch B, Kabani A, Tenenbein M. Source: Annals of Emergency Medicine. 2003 May; 41(5): 601-8. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12712025&dopt=Abstract
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Over-expression of the dominant-negative isoform of Ikaros confers resistance to dexamethasone-induced and anti-IgM-induced apoptosis. Author(s): Sezaki N, Ishimaru F, Takata M, Tabayashi T, Nakase K, Kozuka T, Fujii K, Nakayama H, Teshima T, Harada M, Tanimoto M. Source: British Journal of Haematology. 2003 April; 121(1): 165-9. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12670348&dopt=Abstract
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Overnight dexamethasone suppression test: a reliable screen for Cushing's syndrome in the obese. Author(s): Ness-Abramof R, Nabriski D, Apovian CM, Niven M, Weiss E, Shapiro MS, Shenkman L. Source: Obesity Research. 2002 December; 10(12): 1217-21. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12490665&dopt=Abstract
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Pegylated liposomal doxorubicin, vincristine, and reduced-dose dexamethasone as first-line therapy for multiple myeloma. Author(s): Hussein M. Source: Clinical Lymphoma. 2003 August; 4 Suppl 1: S18-22. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=14556672&dopt=Abstract
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Phase I/II study of hepatic arterial therapy with floxuridine and dexamethasone in combination with intravenous irinotecan as adjuvant treatment after resection of hepatic metastases from colorectal cancer. Author(s): Kemeny N, Jarnagin W, Gonen M, Stockman J, Blumgart L, Sperber D, Hummer A, Fong Y. Source: Journal of Clinical Oncology : Official Journal of the American Society of Clinical Oncology. 2003 September 1; 21(17): 3303-9. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12947066&dopt=Abstract
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Phase II trial of cyclophosphamide, vincristine, and dexamethasone in the treatment of androgen-independent prostate carcinoma. Author(s): Daliani DD, Assikis V, Tu SM, Papandreou CN, Pagliaro LC, Holtkamp T, Wang X, Thall PF, Logothetis CJ. Source: Cancer. 2003 February 1; 97(3): 561-7. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12548597&dopt=Abstract
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Pituitary-adrenal function following dexamethasone-cyclophosphamide pulse therapy for pemphigus. Author(s): Kumrah L, Ramam M, Shah P, Pandey RM, Pasricha JS. Source: The British Journal of Dermatology. 2001 December; 145(6): 944-8. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11899148&dopt=Abstract
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Plasma corticotropin-releasing factor in depressed patients before and after the dexamethasone suppression test. Author(s): Galard R, Catalan R, Castellanos JM, Gallart JM. Source: Biological Psychiatry. 2002 March 15; 51(6): 463-8. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11922880&dopt=Abstract
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Possible exacerbation of adrenal suppression from intrathecal morphine in a patient receiving pulsed dexamethasone for multiple myeloma. Author(s): Rajagopal A, Kala S, Bruera E. Source: Journal of Pain and Symptom Management. 2003 September; 26(3): 786-8. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12967726&dopt=Abstract
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Possible mechanism of dexamethasone therapy for prostate cancer: suppression of circulating level of interleukin-6. Author(s): Akakura K, Suzuki H, Ueda T, Komiya A, Ichikawa T, Igarashi T, Ito H. Source: The Prostate. 2003 July 1; 56(2): 106-9. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12746834&dopt=Abstract
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Postnatal dexamethasone: what is the real cost-benefit ratio? Author(s): Halliday HL. Source: Acta Paediatrica (Oslo, Norway : 1992). 2003 August; 92(8): 888-9. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12948061&dopt=Abstract
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Potentiation of dexamethasone-, paclitaxel-, and Ad-p53-induced apoptosis by Bcl-2 antisense oligodeoxynucleotides in drug-resistant multiple myeloma cells. Author(s): Liu Q, Gazitt Y. Source: Blood. 2003 May 15; 101(10): 4105-14. Epub 2003 January 09. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12521996&dopt=Abstract
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Prenatal dexamethasone treatment of fetuses at risk for congenital adrenal hyperplasia: benefits and concerns. Author(s): Ritzen EM. Source: Seminars in Neonatology : Sn. 2001 August; 6(4): 357-62. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11972437&dopt=Abstract
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Preoperative dexamethasone improves surgical outcome after laparoscopic cholecystectomy: a randomized double-blind placebo-controlled trial. Author(s): Bisgaard T, Klarskov B, Kehlet H, Rosenberg J. Source: Annals of Surgery. 2003 November; 238(5): 651-60. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=14578725&dopt=Abstract
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Prevention of postoperative nausea and vomiting after spinal morphine for Caesarean section: comparison of cyclizine, dexamethasone and placebo. Author(s): Nortcliffe SA, Shah J, Buggy DJ. Source: British Journal of Anaesthesia. 2003 May; 90(5): 665-70. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12697596&dopt=Abstract
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Primary pigmented nodular adrenocortical disease: paradoxical responses of cortisol secretion to dexamethasone occur in vitro and are associated with increased expression of the glucocorticoid receptor. Author(s): Bourdeau I, Lacroix A, Schurch W, Caron P, Antakly T, Stratakis CA. Source: The Journal of Clinical Endocrinology and Metabolism. 2003 August; 88(8): 3931-7. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12915689&dopt=Abstract
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Prolonged culture of HOS 58 human osteosarcoma cells with 1,25-(OH)2-D3, TGFbeta, and dexamethasone reveals physiological regulation of alkaline phosphatase, dissociated osteocalcin gene expression, and protein synthesis and lack of mineralization. Author(s): Siggelkow H, Schenck M, Rohde M, Viereck V, Tauber S, Atkinson MJ, Hufner M. Source: Journal of Cellular Biochemistry. 2002; 85(2): 279-94. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11948684&dopt=Abstract
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Prospective randomized comparison of vincristine, doxorubicin and dexamethasone (VAD) administered as intravenous bolus injection and VAD with liposomal doxorubicin as first-line treatment in multiple myeloma. Author(s): Dimopoulos MA, Pouli A, Zervas K, Grigoraki V, Symeonidis A, Repoussis P, Mitsouli C, Papanastasiou C, Margaritis D, Tokmaktsis A, Katodritou I, Kokkini G, Terpos E, Vyniou N, Tzilianos M, Chatzivassili A, Kyrtsonis MC, Panayiotidis P, Maniatis A; Greek Myeloma Study Group. Source: Annals of Oncology : Official Journal of the European Society for Medical Oncology / Esmo. 2003 July; 14(7): 1039-44. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12853344&dopt=Abstract
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Prospective randomized, double-blind comparative study of dexamethasone, ondansetron, and ondansetron plus dexamethasone as prophylactic antiemetic therapy in patients undergoing day-case gynaecological surgery. Author(s): Thomas R, Jones N. Source: British Journal of Anaesthesia. 2001 October; 87(4): 588-92. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11878729&dopt=Abstract
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Protection of peritoneal macrophages by granulocyte/macrophage colony-stimulating factor (GM-CSF) against dexamethasone suppression of killing of Aspergillus, and the effect of human GM-CSF. Author(s): Brummer E, Maqbool A, Stevens DA. Source: Microbes and Infection / Institut Pasteur. 2002 February; 4(2): 133-8. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11880043&dopt=Abstract
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Pulse dexamethasone, oral steroids and azathioprine in the management of erythema nodosum leprosum. Author(s): Mahajan VK, Sharma NL, Sharma RC, Sharma A. Source: Lepr Rev. 2003 June; 74(2): 171-4. No Abstract Available. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12862259&dopt=Abstract
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Pulsed high-dose dexamethasone therapy in children with chronic idiopathic thrombocytopenic purpura. Author(s): Wali YA, Al Lamki Z, Shah W, Zacharia M, Hassan A. Source: Pediatric Hematology and Oncology. 2002 July-August; 19(5): 329-35. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12078864&dopt=Abstract
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Questions about dexamethasone use for the prevention of anti-SSA related congenital heart block. Author(s): Costedoat-Chalumeau N, Amoura Z, Le Thi Hong D, Wechsler B, Vauthier D, Ghillani P, Papo T, Fain O, Musset L, Piette JC. Source: Annals of the Rheumatic Diseases. 2003 October; 62(10): 1010-2. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12972484&dopt=Abstract
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Randomized controlled trial of three different doses of aerosol beclomethasone versus systemic dexamethasone to promote extubation in ventilated premature infants. Author(s): Rozycki HJ, Byron PR, Elliott GR, Carroll T, Gutcher GR. Source: Pediatric Pulmonology. 2003 May; 35(5): 375-83. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12687595&dopt=Abstract
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Randomized study of dexamethasone treatment for delayed emesis, anorexia and fatigue induced by irinotecan. Author(s): Inoue A, Yamada Y, Matsumura Y, Shimada Y, Muro K, Gotoh M, Hamaguchi T, Mizuno T, Shirao K. Source: Supportive Care in Cancer : Official Journal of the Multinational Association of Supportive Care in Cancer. 2003 August; 11(8): 528-32. Epub 2003 July 03. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12844250&dopt=Abstract
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Randomized study of IVIg and high-dose dexamethasone therapy for children with chronic idiopathic thrombocytopenic purpura. Author(s): Hedlund-Treutiger I, Henter JI, Elinder G. Source: Journal of Pediatric Hematology/Oncology : Official Journal of the American Society of Pediatric Hematology/Oncology. 2003 February; 25(2): 139-44. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12571466&dopt=Abstract
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Randomized, double-blind, dose-finding study of dexamethasone in preventing acute emesis induced by anthracyclines, carboplatin, or cyclophosphamide:. Author(s): Italian Group For Antiemetic Research. Source: Journal of Clinical Oncology : Official Journal of the American Society of Clinical Oncology. 2004 February 15; 22(4): 725-9. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=14966097&dopt=Abstract
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Rapid non-genomic inhibition of ATP-induced Cl- secretion by dexamethasone in human bronchial epithelium. Author(s): Urbach V, Walsh DE, Mainprice B, Bousquet J, Harvey BJ. Source: The Journal of Physiology. 2002 December 15; 545(Pt 3): 869-78. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12482892&dopt=Abstract
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Rat and human aortic smooth muscle cells display differing migration and matrix metalloproteinase activities in response to dexamethasone. Author(s): Pross C, Farooq MM, Lane JS, Angle N, Tomono CK, Xavier AE, Freischlag JA, Collins AE, Law RE, Gelabert HA. Source: Journal of Vascular Surgery : Official Publication, the Society for Vascular Surgery [and] International Society for Cardiovascular Surgery, North American Chapter. 2002 June; 35(6): 1253-9. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12042738&dopt=Abstract
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Reduction of tumor necrosis factor induced nuclear factor-kappaB nuclear translocation and DNA binding by dexamethasone in human osteoarthritic synovial tissue explants. Author(s): Lehmann T, Murphy C, Zahra DG, Handel ML. Source: The Journal of Rheumatology. 2002 April; 29(4): 787-95. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11950023&dopt=Abstract
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Regulation of bronchoalveolar macrophage proinflammatory cytokine production by dexamethasone and granulocyte-macrophage colony-stimulating factor after stimulation by Aspergillus conidia or lipopolysaccharide. Author(s): Kamberi M, Brummer E, Stevens DA. Source: Cytokine. 2002 July 7; 19(1): 14-20. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12200108&dopt=Abstract
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Regulation of E-cadherin expression by dexamethasone and tumour necrosis factoralpha in nasal epithelium. Author(s): Carayol N, Vachier I, Campbell A, Crampette L, Bousquet J, Godard P, Chanez P. Source: The European Respiratory Journal : Official Journal of the European Society for Clinical Respiratory Physiology. 2002 December; 20(6): 1430-6. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12503700&dopt=Abstract
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Regulation of kinin receptors in airway epithelial cells by inflammatory cytokines and dexamethasone. Author(s): Newton R, Eddleston J, Haddad el-B, Hawisa S, Mak J, Lim S, Fox AJ, Donnelly LE, Chung KF. Source: European Journal of Pharmacology. 2002 April 26; 441(3): 193-202. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12063092&dopt=Abstract
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Respiratory burst activity in bronchopulmonary dysplasia and changes with dexamethasone. Author(s): Ballabh P, Simm M, Kumari J, Califano C, Aghai Z, Laborada G, Sison C, Cunningham-Rundles S. Source: Pediatric Pulmonology. 2003 May; 35(5): 392-9. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12687597&dopt=Abstract
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Rituximab, Cyclophosphamide, Dexamethasone (RCD) regimen induces cure in WSU-WM xenograft model and a partial remission in previously treated Waldenstrom's macroglobulinemia patient. Author(s): Mohammad RM, Aboukameel A, Nabha S, Ibrahim D, Al-Katib A. Source: Journal of Drug Targeting. 2002 August; 10(5): 405-10. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12442811&dopt=Abstract
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Role of dexamethasone in acute bacterial meningitis in adults. Author(s): Ahsan T, Shahid M, Mahmood T, Jabeen R, Jehangir U, Saleem M, Ahmed N, Shaheer A. Source: J Pak Med Assoc. 2002 June; 52(6): 233-9. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12481630&dopt=Abstract
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Salivary cortisol levels and the cortisol response to dexamethasone before and after EMDR: a case report. Author(s): Heber R, Kellner M, Yehuda R. Source: Journal of Clinical Psychology. 2002 December; 58(12): 1521-30. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12455019&dopt=Abstract
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Salivary cortisol responses to dexamethasone in adolescents with posttraumatic stress disorder. Author(s): Lipschitz DS, Rasmusson AM, Yehuda R, Wang S, Anyan W, Gueoguieva R, Grilo CM, Fehon DC, Southwick SM. Source: Journal of the American Academy of Child and Adolescent Psychiatry. 2003 November; 42(11): 1310-7. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=14566168&dopt=Abstract
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Short- and long-term effects of neonatal glucocorticoid therapy: is hydrocortisone an alternative to dexamethasone? Author(s): van der Heide-Jalving M, Kamphuis PJ, van der Laan MJ, Bakker JM, Wiegant VM, Heijnen CJ, Veen S, van Bel F. Source: Acta Paediatrica (Oslo, Norway : 1992). 2003 July; 92(7): 827-35. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12892163&dopt=Abstract
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Short-term effects of prednisolone and dexamethasone on circulating concentrations of leptin and sex hormone-binding globulin in children being treated for acute lymphoblastic leukaemia. Author(s): Wallace AM, Tucker P, Williams DM, Hughes IA, Ahmed SF. Source: Clinical Endocrinology. 2003 June; 58(6): 770-6. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12780755&dopt=Abstract
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Short-term effects on linear growth and bone turnover in children randomized to receive prednisolone or dexamethasone. Author(s): Ahmed SF, Tucker P, Mushtaq T, Wallace AM, Williams DM, Hughes IA. Source: Clinical Endocrinology. 2002 August; 57(2): 185-91. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12153596&dopt=Abstract
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Small-dose dexamethasone reduces nausea and vomiting after laparoscopic cholecystectomy: a comparison of tropisetron with saline. Author(s): Wang JJ, Ho ST, Uen YH, Lin MT, Chen KT, Huang JC, Tzeng JI. Source: Anesthesia and Analgesia. 2002 July; 95(1): 229-32, Table of Contents. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12088975&dopt=Abstract
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Soluble E-selectin, soluble L-selectin and soluble ICAM-1 in bronchopulmonary dysplasia, and changes with dexamethasone. Author(s): Ballabh P, Kumari J, Krauss AN, Shin JJ, Jain A, Auld PA, Lesser ML, Cunningham-Rundles S. Source: Pediatrics. 2003 March; 111(3): 461-8. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12612222&dopt=Abstract
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Spontaneous apoptosis in primary cultures of human and rat hepatocytes: molecular mechanisms and regulation by dexamethasone. Author(s): Bailly-Maitre B, de Sousa G, Zucchini N, Gugenheim J, Boulukos KE, Rahmani R. Source: Cell Death and Differentiation. 2002 September; 9(9): 945-55. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12181745&dopt=Abstract
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Statin-induced apoptosis of vascular endothelial cells is blocked by dexamethasone. Author(s): Newton CJ, Ran G, Xie YX, Bilko D, Burgoyne CH, Adams I, Abidia A, McCollum PT, Atkin SL. Source: The Journal of Endocrinology. 2002 July; 174(1): 7-16. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12098658&dopt=Abstract
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Stevens-Johnson syndrome with idiopathic thrombocytopenic purpura treated with dexamethasone pulse therapy. Author(s): Barman KD, Verma KK, Agrawal S, Agarwalla A, Rijal A. Source: The Journal of Dermatology. 2003 January; 30(1): 54-8. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12598710&dopt=Abstract
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Stimulation of apoptosis in human granulosa cells from in vitro fertilization patients and its prevention by dexamethasone: involvement of cell contact and bcl-2 expression. Author(s): Sasson R, Amsterdam A. Source: The Journal of Clinical Endocrinology and Metabolism. 2002 July; 87(7): 3441-51. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12107264&dopt=Abstract
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Supra-tarsal injection of dexamethasone in the treatment of patients with refractory vernal keratoconjunctivitis. Author(s): Lisanework M. Source: Ethiop Med J. 2003 January; 41(1): 19-24. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12764997&dopt=Abstract
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Synergistic inhibitory activities of interleukin-10 and dexamethasone on human CD4+ T cells. Author(s): Brunetti M, Mascetra N, Martelli N, Ranelletti FO, Musiani P, Aiello FB. Source: Transplantation. 2002 October 27; 74(8): 1152-8. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12438963&dopt=Abstract
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Thalidomide alone or with dexamethasone for previously untreated multiple myeloma. Author(s): Weber D, Rankin K, Gavino M, Delasalle K, Alexanian R. Source: Journal of Clinical Oncology : Official Journal of the American Society of Clinical Oncology. 2003 January 1; 21(1): 16-9. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12506164&dopt=Abstract
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Thalidomide and dexamethasone for resistant multiple myeloma. Author(s): Anagnostopoulos A, Weber D, Rankin K, Delasalle K, Alexanian R. Source: British Journal of Haematology. 2003 June; 121(5): 768-71. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12780791&dopt=Abstract
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Thalidomide and dexamethasone therapy of myeloma in a patient with previously untreated B-chronic lymphocytic leukemia. Author(s): Barton JC. Source: American Journal of Hematology. 2003 November; 74(3): 205-7. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=14587053&dopt=Abstract
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Thalidomide in combination with cyclophosphamide and dexamethasone (thacydex) is effective in soft-tissue plasmacytomas. Author(s): Gonzalez-Porras JR, Gonzalez M, Garcia-Sanz R, San Miguel JF. Source: British Journal of Haematology. 2002 December; 119(3): 883-4. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12437681&dopt=Abstract
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The alerting effects of dexamethasone. Author(s): Meixner R, Gerhardstein R, Day R, Nykamp CK, Syron ML, Rosenthal L. Source: Psychophysiology. 2003 March; 40(2): 254-9. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12820866&dopt=Abstract
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The chemokine receptor CCR8 mediates rescue from dexamethasone-induced apoptosis via an ERK-dependent pathway. Author(s): Spinetti G, Bernardini G, Camarda G, Mangoni A, Santoni A, Capogrossi MC, Napolitano M. Source: Journal of Leukocyte Biology. 2003 January; 73(1): 201-7. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12525579&dopt=Abstract
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The combination of thalidomide, cyclophosphamide and dexamethasone (ThaCyDex) is feasible and can be an option for relapsed/refractory multiple myeloma. Author(s): Garcia-Sanz R, Gonzalez-Fraile MI, Sierra M, Lopez C, Gonzalez M, San Miguel JF. Source: The Hematology Journal : the Official Journal of the European Haematology Association / Eha. 2002; 3(1): 43-8. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11960395&dopt=Abstract
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The combined dexamethasone-CRH test before and after repetitive transcranial magnetic stimulation (rTMS) in major depression. Author(s): Zwanzger P, Baghai TC, Padberg F, Ella R, Minov C, Mikhaiel P, Schule C, Thoma H, Rupprecht R. Source: Psychoneuroendocrinology. 2003 April; 28(3): 376-85. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12573303&dopt=Abstract
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The cortisol and glucocorticoid receptor response to low dose dexamethasone administration in aging combat veterans and holocaust survivors with and without posttraumatic stress disorder. Author(s): Yehuda R, Halligan SL, Grossman R, Golier JA, Wong C. Source: Biological Psychiatry. 2002 September 1; 52(5): 393-403. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12242055&dopt=Abstract
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The dexamethasone suppression test and CSF-5-HIAA in relation to suicidality and depression in suicide attempters. Author(s): Westrin A, Nimeus A. Source: European Psychiatry : the Journal of the Association of European Psychiatrists. 2003 June; 18(4): 166-71. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12814849&dopt=Abstract
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The dose response and effects of dexamethasone on bupivacaine microcapsules for intercostal blockade (T9 to T11) in healthy volunteers. Author(s): Kopacz DJ, Lacouture PG, Wu D, Nandy P, Swanton R, Landau C. Source: Anesthesia and Analgesia. 2003 February; 96(2): 576-82, Table of Contents. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12538215&dopt=Abstract
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The dual role of dexamethasone on anti-inflammation and outflow resistance demonstrated in cultured human trabecular meshwork cells. Author(s): Leung YF, Tam PO, Lee WS, Lam DS, Yam HF, Fan BJ, Tham CC, Chua JK, Pang CP. Source: Molecular Vision [electronic Resource]. 2003 September 5; 9: 425-39. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12963864&dopt=Abstract
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The effect of cyclophosphamide with and without dexamethasone on cytochrome P450 3A4 and 2B6 in human hepatocytes. Author(s): Lindley C, Hamilton G, McCune JS, Faucette S, Shord SS, Hawke RL, Wang H, Gilbert D, Jolley S, Yan B, LeCluyse EL. Source: Drug Metabolism and Disposition: the Biological Fate of Chemicals. 2002 July; 30(7): 814-22. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12065440&dopt=Abstract
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The effect of dexamethasone on side effects after coronary revascularization procedures. Author(s): Halvorsen P, Raeder J, White PF, Almdahl SM, Nordstrand K, Saatvedt K, Veel T. Source: Anesthesia and Analgesia. 2003 June; 96(6): 1578-83, Table of Contents. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12760978&dopt=Abstract
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The effect of dexamethasone on the longevity of syringe driver subcutaneous sites in palliative care patients. Author(s): Reymond L, Charles MA, Bowman J, Treston P. Source: The Medical Journal of Australia. 2003 May 19; 178(10): 486-9. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12741933&dopt=Abstract
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The effect of dexamethasone upon patient-controlled analgesia-related nausea and vomiting. Author(s): Lee Y, Lin YS, Chen YH. Source: Anaesthesia. 2002 July; 57(7): 705-9. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12109416&dopt=Abstract
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The effects of dexamethasone on leukemic cells derived from patients with AML. Author(s): Ovali E, Ozdemir F, Aydin F, Kavgaci H, Tekelioglu Y, Buyukcelik A, Yilmaz M. Source: J Exp Clin Cancer Res. 2003 March; 22(1): 85-9. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12725327&dopt=Abstract
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The effects of dexamethasone, bupivacaine and topical lidocaine spray on pain after tonsillectomy. Author(s): Kaygusuz I, Susaman N. Source: International Journal of Pediatric Otorhinolaryngology. 2003 July; 67(7): 737-42. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12791448&dopt=Abstract
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The IL-6 receptor super-antagonist Sant7 enhances antiproliferative and apoptotic effects induced by dexamethasone and zoledronic acid on multiple myeloma cells. Author(s): Tassone P, Galea E, Forciniti S, Tagliaferri P, Venuta S. Source: International Journal of Oncology. 2002 October; 21(4): 867-73. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12239628&dopt=Abstract
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The low dose dexamethasone suppression test: effect of time of administration and dose. Author(s): Barton C, March S, Wittert GA. Source: J Endocrinol Invest. 2002 April; 25(4): Rc10-2. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12030615&dopt=Abstract
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The pharmacokinetic and biological activity profile of dexamethasone targeted to sinusoidal endothelial and Kupffer cells. Author(s): Melgert BN, Weert B, Schellekens H, Meijer DK, Poelstra K. Source: Journal of Drug Targeting. 2003 January; 11(1): 1-10. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12852435&dopt=Abstract
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The prophylactic effect of tropisetron on epidural morphine-related nausea and vomiting: a comparison of dexamethasone with saline. Author(s): Wang JJ, Tzeng JI, Ho ST, Chen JY, Chu CC, So EC. Source: Anesthesia and Analgesia. 2002 March; 94(3): 749-53; Table of Contents. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11867410&dopt=Abstract
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The tissue level of dexamethasone in human brain tumors is about 1000 times lower than the cytotoxic concentration in cell culture. Author(s): Nestler U, Winking M, Boker DK. Source: Neurological Research. 2002 July; 24(5): 479-82. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12117318&dopt=Abstract
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The value of the low-dose dexamethasone suppression test in the differential diagnosis of hyperandrogenism in women. Author(s): Rosenfield RL, Barnes RB, Ehrmann DA, Toledano AY. Source: The Journal of Clinical Endocrinology and Metabolism. 2003 December; 88(12): 6115; Author Reply 6115-6. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=14671222&dopt=Abstract
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The value of the low-dose dexamethasone suppression test in the differential diagnosis of hyperandrogenism in women. Author(s): Kaltsas GA, Isidori AM, Kola BP, Skelly RH, Chew SL, Jenkins PJ, Monson JP, Grossman AB, Besser GM. Source: The Journal of Clinical Endocrinology and Metabolism. 2003 June; 88(6): 2634-43. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12788867&dopt=Abstract
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Therapeutic effects on intestinal Behcet's disease of an intravenous drug delivery system using dexamethasone incorporated in lipid emulsion. Author(s): Nakase H, Okazaki K, Kawanami C, Uchida K, Ohana M, Uose S, Nishi T, Itoh T, Okano A, Nishio A, Takakuwa H, Chiba T. Source: Journal of Gastroenterology and Hepatology. 2001 November; 16(11): 1306-8. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11903753&dopt=Abstract
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Thromboembolic events in children with acute lymphoblastic leukemia (BFM protocols): prednisone versus dexamethasone administration. Author(s): Nowak-Gottl U, Ahlke E, Fleischhack G, Schwabe D, Schobess R, Schumann C, Junker R. Source: Blood. 2003 April 1; 101(7): 2529-33. Epub 2002 November 27. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12517808&dopt=Abstract
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Time-intensified dexamethasone/cisplatin/cytarabine: an effective salvage therapy with low toxicity in patients with relapsed and refractory Hodgkin's disease. Author(s): Josting A, Rudolph C, Reiser M, Mapara M, Sieber M, Kirchner HH, Dorken B, Hossfeld DK, Diehl V, Engert A; Participating Centers. Source: Annals of Oncology : Official Journal of the European Society for Medical Oncology / Esmo. 2002 October; 13(10): 1628-35. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12377653&dopt=Abstract
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Tissue differential microarray analysis of dexamethasone induction reveals potential mechanisms of steroid glaucoma. Author(s): Lo WR, Rowlette LL, Caballero M, Yang P, Hernandez MR, Borras T. Source: Investigative Ophthalmology & Visual Science. 2003 February; 44(2): 473-85. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12556371&dopt=Abstract
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Topical ciprofloxacin/dexamethasone is superior to ciprofloxacin alone in pediatric patients with acute otitis media and otorrhea through tympanostomy tubes. Author(s): Roland PS, Anon JB, Moe RD, Conroy PJ, Wall GM, Dupre SJ, Krueger KA, Potts S, Hogg G, Stroman DW. Source: The Laryngoscope. 2003 December; 113(12): 2116-22. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=14660913&dopt=Abstract
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Topical ciprofloxacin/dexamethasone otic suspension is superior to ofloxacin otic solution in the treatment of children with acute otitis media with otorrhea through tympanostomy tubes. Author(s): Roland PS, Kreisler LS, Reese B, Anon JB, Lanier B, Conroy PJ, Wall GM, Dupre SJ, Potts S, Hogg G, Stroman DW, McLean C. Source: Pediatrics. 2004 January; 113(1 Pt 1): E40-6. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=14702493&dopt=Abstract
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Transdermal electromotive administration of verapamil and dexamethasone for Peyronie's disease. Author(s): Di Stasi SM, Giannantoni A, Capelli G, Jannini EA, Virgili G, Storti L, Vespasiani G. Source: Bju International. 2003 June; 91(9): 825-9. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12780842&dopt=Abstract
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Transsphenoidal microsurgical treatment of Cushing disease: postoperative assessment of surgical efficacy by application of an overnight low-dose dexamethasone suppression test. Author(s): Chen JC, Amar AP, Choi S, Singer P, Couldwell WT, Weiss MH. Source: Journal of Neurosurgery. 2003 May; 98(5): 967-73. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12744355&dopt=Abstract
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Treating preterm infants at risk for chronic lung disease with dexamethasone leads to an impaired quality of general movements. Author(s): Bos AF, Dibiasi J, Tiessen AH, Bergman KA. Source: Biology of the Neonate. 2002; 82(3): 155-8. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12373065&dopt=Abstract
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Treatment of Waldenstrom's macroglobulinemia with clarithromycin, low-dose thalidomide, and dexamethasone. Author(s): Coleman M, Leonard J, Lyons L, Szelenyi H, Niesvizky R. Source: Seminars in Oncology. 2003 April; 30(2): 270-4. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12720151&dopt=Abstract
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Treatment of Waldenstrom's macroglobulinemia with single-agent thalidomide or with the combination of clarithromycin, thalidomide and dexamethasone. Author(s): Dimopoulos MA, Tsatalas C, Zomas A, Hamilos G, Panayiotidis P, Margaritis D, Matsouka C, Economopoulos T, Anagnostopoulos N. Source: Seminars in Oncology. 2003 April; 30(2): 265-9. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12720150&dopt=Abstract
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Troglitazone induces CYP3A4 activity leading to falsely abnormal dexamethasone suppression test. Author(s): Dimaraki EV, Jaffe CA. Source: The Journal of Clinical Endocrinology and Metabolism. 2003 July; 88(7): 3113-6. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12843151&dopt=Abstract
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Tropisetron and dexamethasone administered twice daily for the prevention of acute emesis in patients treated with continuous infusion of Cisplatin-Doxorubicin and high-dose Ifosfamide over 48, 24, and 120 hours. Author(s): Forni C, Loro L, Mazzei T, Beghelli C, Biolchini A, Tremosini M, Triggiani A, Bacci G. Source: Cancer Nursing. 2003 August; 26(4): 331-4. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12886124&dopt=Abstract
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Use of dexamethasone and clomiphene citrate in the treatment of clomiphene citrateresistant patients with polycystic ovary syndrome and normal dehydroepiandrosterone sulfate levels: a prospective, double-blind, placebocontrolled trial. Author(s): Parsanezhad ME, Alborzi S, Motazedian S, Omrani G. Source: Fertility and Sterility. 2002 November; 78(5): 1001-4. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12413984&dopt=Abstract
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Use of melphalan, thalidomide, and dexamethasone in treatment of refractory and relapsed multiple myeloma. Author(s): Srkalovic G, Elson P, Trebisky B, Karam MA, Hussein MA. Source: Medical Oncology (Northwood, London, England). 2002; 19(4): 219-26. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12512915&dopt=Abstract
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CHAPTER 2. NUTRITION AND DEXAMETHASONE Overview In this chapter, we will show you how to find studies dedicated specifically to nutrition and dexamethasone.
Finding Nutrition Studies on Dexamethasone 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 “dexamethasone” (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 “dexamethasone” (or a synonym): •
Ampicillin pharmacokinetics after single administration and after C0-administration of metamizole or dexamethasone. Author(s): Thracian University - Faculty of Veterinary Medicine, Stara Zagora (Bulgaria) Source: Haritova, A. Pashov, D. Lashev, L. Bulgarian-Journal-of-Veterinary-Medicine. (2000). volume 3(4) page 185-198.
Additional physician-oriented references include: •
Comparative study of low-dose oral granisetron plus dexamethasone and high-dose metoclopramide plus dexamethasone in prevention of nausea and vomiting induced by CHOP-therapy in young patients with non-Hodgkin's lymphoma. Author(s): Department of Medicine, Phramongkutklao Hospital, Bangkok 10400, Thailand. Source: Numbenjapon, T Sriswasdi, C Mongkonsritragoon, W Leelasiri, A Prayoonwiwat, W J-Med-Assoc-Thai. 2002 November; 85(11): 1156-63 0125-2208
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Dexamethasone enhances follicle stimulating hormone-induced P450scc mRNA expression and progesterone production in pig granulosa cells. Author(s): Department of Medical Research, Chang-Hua Christian Hospital, Taiwan, ROC. Source: Yang, J G Yu, C C Li, P S Chin-J-Physiol. 2001 September 30; 44(3): 111-9 03044920
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Differential expression of VEGF receptors in adrenal atrophy induced by dexamethasone: a protective role of ACTH. Source:
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Effect of prostaglandin and dexamethasone injection on farrowing and piglet neonatal growth. Author(s): Dipartimento di Salute Animale, Facolta di Medicina Veterinaria, Parma, Italy. Source: De Rensis, F Sottocorona, M Kirkwood, R N Vet-Rec. 2002 September 14; 151(11): 330-1 0042-4900
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In vitro osteogenic differentiation of rat bone marrow cells subcultured with and without dexamethasone. Author(s): Department of Biomaterials, College of Dental Science, University Medical Center Nijmegen, The Netherlands. Source: Ter Brugge, P J Jansen, J A Tissue-Eng. 2002 April; 8(2): 321-31 1076-3279
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Inhibition of 3alpha/beta,20beta-hydroxysteroid dehydrogenase by dexamethasone, glycyrrhetinic acid and spironolactone is attenuated by deletion of 12 carboxylterminal residues. Author(s): Department of Physiological Chemistry, Faculty of Pharmaceutical Sciences, Toyama Medical and Pharmaceutical University, Sugitani, Japan. Source: Itoda, M Takase, N Nakajin, S Biol-Pharm-Bull. 2002 September; 25(9): 1220-2 0918-6158
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Intermediate doses of melphalan and dexamethasone are better than vincristine, adriamycin, and dexamethasone (VAD) and polychemotherapy for the treatment of primary plasma cell leukemia. Author(s): Department of Hematology, Hospital de Especialidades Centro Medico Nacional La Raza, Instituto Mexicano del Seguro Social, Apartado Postal 14-878, Codigo postal 07001, Mexico D.F., Mexico.
[email protected] Source: Vela Ojeda, J Garcia Ruiz Esparza, M A Rosas Cabral, A Padilla Gonzalez, Y Garcia Chavez, J Tripp Villanueva, F Sanchez Cortes, E Ayala Sanchez, M Garcia Leon, L D Montiel Cervantes, L Rubio Borja, M E Ann-Hematol. 2002 July; 81(7): 362-7 0939-5555
Federal Resources on Nutrition In addition to the IBIDS, the United States Department of Health and Human Services (HHS) and the United States Department of Agriculture (USDA) provide many sources of information on general nutrition and health. Recommended resources include: •
healthfinder®, HHS’s gateway to health information, including diet and nutrition: http://www.healthfinder.gov/scripts/SearchContext.asp?topic=238&page=0
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The United States Department of Agriculture’s Web site dedicated to nutrition information: www.nutrition.gov
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The Food and Drug Administration’s Web site for federal food safety information: www.foodsafety.gov
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The National Action Plan on Overweight and Obesity sponsored by the United States Surgeon General: http://www.surgeongeneral.gov/topics/obesity/
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The Center for Food Safety and Applied Nutrition has an Internet site sponsored by the Food and Drug Administration and the Department of Health and Human Services: http://vm.cfsan.fda.gov/
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Center for Nutrition Policy and Promotion sponsored by the United States Department of Agriculture: http://www.usda.gov/cnpp/
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Food and Nutrition Information Center, National Agricultural Library sponsored by the United States Department of Agriculture: http://www.nal.usda.gov/fnic/
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Food and Nutrition Service sponsored by the United States Department of Agriculture: http://www.fns.usda.gov/fns/
Additional Web Resources A number of additional Web sites offer encyclopedic information covering food and nutrition. The following is a representative sample: •
AOL: http://search.aol.com/cat.adp?id=174&layer=&from=subcats
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Family Village: http://www.familyvillage.wisc.edu/med_nutrition.html
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Google: http://directory.google.com/Top/Health/Nutrition/
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Healthnotes: http://www.healthnotes.com/
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Open Directory Project: http://dmoz.org/Health/Nutrition/
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Yahoo.com: http://dir.yahoo.com/Health/Nutrition/
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WebMD®Health: http://my.webmd.com/nutrition
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WholeHealthMD.com: http://www.wholehealthmd.com/reflib/0,1529,00.html
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CHAPTER 3. ALTERNATIVE DEXAMETHASONE
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Overview In this chapter, we will begin by introducing you to official information sources on complementary and alternative medicine (CAM) relating to dexamethasone. 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 dexamethasone 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 “dexamethasone” (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 dexamethasone: •
A combination of dexamethasone, cyclophosphamide, etoposide, and cisplatin is less toxic and more effective than high-dose cyclophosphamide for peripheral stem cell mobilization in multiple myeloma. Author(s): Corso A, Arcaini L, Caberlon S, Zappasodi P, Mangiacavalli S, Lorenzi A, Rusconi C, Troletti D, Maiocchi MA, Pascutto C, Morra E, Lazzarino M. Source: Haematologica. 2002 October; 87(10): 1041-5. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12368158&dopt=Abstract
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A dexamethasone, vinblastine, cyclophosphamide, etoposide, methotrexate and bleomycin (D-VICEMB) protocol as first-line treatment of patients aged 70 years or older affected by intermediate/high grade non-Hodgkin's lymphoma. Author(s): Angrilli F, Pennese E, Di Marzio A, Liberatore E, Di Lorenzo R, Fioritoni G.
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Source: Haematologica. 2002 November; 87(11): 1227-9. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12414356&dopt=Abstract •
A germ-line p53 mutation accelerates pulmonary tumorigenesis: p53-independent efficacy of chemopreventive agents green tea or dexamethasone/myo-inositol and chemotherapeutic agents taxol or adriamycin. Author(s): Zhang Z, Liu Q, Lantry LE, Wang Y, Kelloff GJ, Anderson MW, Wiseman RW, Lubet RA, You M. Source: Cancer Research. 2000 February 15; 60(4): 901-7. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10706103&dopt=Abstract
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A new multidrug reinduction protocol with topotecan, vinorelbine, thiotepa, dexamethasone, and gemcitabine for relapsed or refractory acute leukemia. Author(s): Kolb EA, Steinherz PG. Source: Leukemia : Official Journal of the Leukemia Society of America, Leukemia Research Fund, U.K. 2003 October; 17(10): 1967-72. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=14513046&dopt=Abstract
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A Phase II trial of pegylated liposomal doxorubicin, vincristine, and reduced-dose dexamethasone combination therapy in newly diagnosed multiple myeloma patients. Author(s): Hussein MA, Wood L, Hsi E, Srkalovic G, Karam M, Elson P, Bukowski RM. Source: Cancer. 2002 November 15; 95(10): 2160-8. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12412170&dopt=Abstract
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Administration of a modified chemotherapeutic regimen containing vincristine, liposomal doxorubicin and dexamethasone to multiple myeloma patients: preliminary data. Author(s): Tsiara SN, Kapsali E, Christou L, Panteli A, Pritsivelis N, Bourantas KL. Source: European Journal of Haematology. 2000 August; 65(2): 118-22. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10966172&dopt=Abstract
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An early oxygen-dependent step is required for dexamethasone-induced apoptosis of immature mouse thymocytes. Author(s): Torres-Roca JF, Tung JW, Greenwald DR, Brown JM, Herzenberg LA, Herzenberg LA, Katsikis PD. Source: Journal of Immunology (Baltimore, Md. : 1950). 2000 November 1; 165(9): 482230. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11046005&dopt=Abstract
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Bi-weekly epirubicin, etoposide and low-dose dexamethasone for hormone-refractory prostate cancer. Author(s): Odrazka K, Vaculikova M, Petera J, Moravek P, Prosvic P, Zoul Z, Rydel L, Brodak M, Veselsky Z, Louda M, Simakova E.
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Source: International Journal of Urology : Official Journal of the Japanese Urological Association. 2003 July; 10(7): 387-91. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12823694&dopt=Abstract •
Characterization of new selective somatostatin receptor subtype-2 (sst2) antagonists, BIM-23627 and BIM-23454. Effects of BIM-23627 on GH release in anesthetized male rats after short-term high-dose dexamethasone treatment. Author(s): Tulipano G, Soldi D, Bagnasco M, Culler MD, Taylor JE, Cocchi D, Giustina A. Source: Endocrinology. 2002 April; 143(4): 1218-24. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11897676&dopt=Abstract
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Cognitive sequelae in children treated for acute lymphoblastic leukemia with dexamethasone or prednisone. Author(s): Waber DP, Carpentieri SC, Klar N, Silverman LB, Schwenn M, Hurwitz CA, Mullenix PJ, Tarbell NJ, Sallan SE. Source: Journal of Pediatric Hematology/Oncology : Official Journal of the American Society of Pediatric Hematology/Oncology. 2000 May-June; 22(3): 206-13. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10864051&dopt=Abstract
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Combination therapy with irinotecan (CPT-11), mitoxantrone, and dexamethasone in relapsed or refractory non-Hodgkin's lymphoma: a pilot study. Author(s): Niitsu N, Iijima K, Chizuka A. Source: Annals of Hematology. 2001 July; 80(7): 411-6. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11529467&dopt=Abstract
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Comparative study of low-dose oral granisetron plus dexamethasone and high-dose metoclopramide plus dexamethasone in prevention of nausea and vomiting induced by CHOP-therapy in young patients with non-Hodgkin's lymphoma. Author(s): Numbenjapon T, Sriswasdi C, Mongkonsritragoon W, Leelasiri A, Prayoonwiwat W. Source: J Med Assoc Thai. 2002 November; 85(11): 1156-63. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12546311&dopt=Abstract
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Comparison of signaling pathways involved in apoptosis of a thymocyte hybridoma triggered by a rat thymic medullary epithelial cell line, dexamethasone or T-cell receptor cross-linking. Author(s): Popovic P, Colic M, Vucevic D, Gasic S, Pavicic L. Source: Immunology Letters. 2000 May 1; 72(2): 83-91. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10841942&dopt=Abstract
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Comparison of two different schedules of granulocyte-colony-stimulating factor during treatment for acute lymphocytic leukemia with a hyper-CVAD
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(cyclophosphamide, doxorubicin, vincristine, and dexamethasone) regimen. Author(s): Weiser MA, O'Brien S, Thomas DA, Pierce SA, Lam TP, Kantarjian HM. Source: Cancer. 2002 January 15; 94(2): 285-91. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11900213&dopt=Abstract •
Complete protection by high-dose dexamethasone against the hepatotoxicity of the novel antitumor drug yondelis (ET-743) in the rat. Author(s): Donald S, Verschoyle RD, Greaves P, Gant TW, Colombo T, Zaffaroni M, Frapolli R, Zucchetti M, D'Incalci M, Meco D, Riccardi R, Lopez-Lazaro L, Jimeno J, Gescher AJ. Source: Cancer Research. 2003 September 15; 63(18): 5902-8. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=14522916&dopt=Abstract
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Continuous infusion of vincristine-doxorubicin with bolus of dexamethasone(VAD) alternated with CHEP in the treatment of patients over 60 years old with aggressive non-Hodgkin's lymphoma. Author(s): Cartron G, Voillat L, Desablens B, Le Maignan C, Milpied N, Foussard C, Dugay J, Maakaroun A, De Muret A, Colombat P; GOELAMS Group. Source: Leukemia & Lymphoma. 2001 February; 40(5-6): 529-40. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11426526&dopt=Abstract
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Cyclosporin A combined with vincristine, doxorubicin and dexamethasone (VAD) compared with VAD alone in patients with advanced refractory multiple myeloma: an EORTC-HOVON randomized phase III study (06914). Author(s): Sonneveld P, Suciu S, Weijermans P, Beksac M, Neuwirtova R, Solbu G, Lokhorst H, van der Lelie J, Dohner H, Gerhartz H, Segeren CM, Willemze R, Lowenberg B; European Organization for Research and Treatment of Cancer (EORTC); Leukaemia Cooperative Group (LCG); Dutch Haemato-Oncology Cooperative Study Group (HOVON). Source: British Journal of Haematology. 2001 December; 115(4): 895-902. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11843823&dopt=Abstract
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DCEP (dexamethasone, cyclophosphamide, etoposide, and cisplatin) is an effective regimen for peripheral blood stem cell collection in multiple myeloma. Author(s): Lazzarino M, Corso A, Barbarano L, Alessandrino EP, Cairoli R, Pinotti G, Ucci G, Uziel L, Rodeghiero F, Fava S, Ferrari D, Fiumano M, Frigerio G, Isa L, Luraschi A, Montanara S, Morandi S, Perego D, Santagostino A, Savare M, Vismara A, Morra E. Source: Bone Marrow Transplantation. 2001 November; 28(9): 835-9. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11781643&dopt=Abstract
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Delineation of signalling pathway leading to antioxidant-dependent inhibition of dexamethasone-mediated muscle cell death. Author(s): Orzechowski A, Jank M, Gajkowska B, Sadkowski T, Godlewski MM, Ostaszewski P.
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Source: Journal of Muscle Research and Cell Motility. 2003; 24(1): 33-53. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12953835&dopt=Abstract •
Dexamethasone, carmustine, etoposide, cytarabine, and melphalan (dexa-BEAM) followed by high-dose chemotherapy and stem cell rescue--a highly effective regimen for patients with refractory or relapsed indolent lymphoma. Author(s): Josting A, Reiser M, Wickramanayake PD, Rueffer U, Draube A, Sohngen D, Tesch H, Wolf J, Diehl V, Engert A. Source: Leukemia & Lymphoma. 2000 March; 37(1-2): 115-23. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10721775&dopt=Abstract
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Dexamethasone, paclitaxel, etoposide, cyclophosphamide (d-TEC) and G-CSF for stem cell mobilisation in multiple myeloma. Author(s): Bilgrami S, Bona RD, Edwards RL, Li Z, Naqvi B, Shaikh A, Furlong F, Fox J, Clive J, Tutschka PJ. Source: Bone Marrow Transplantation. 2001 July; 28(2): 137-43. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11509931&dopt=Abstract
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Dexamethasone-associated toxicity during induction chemotherapy for childhood acute lymphoblastic leukemia is augmented by concurrent use of daunomycin. Author(s): Belgaumi AF, Al-Bakrah M, Al-Mahr M, Al-Jefri A, Al-Musa A, Saleh M, Salim MF, Osman M, Osman L, El-Solh H. Source: Cancer. 2003 June 1; 97(11): 2898-903. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12767105&dopt=Abstract
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Dexamethasone-induced gene 2 (dig2) is a novel pro-survival stress gene induced rapidly by diverse apoptotic signals. Author(s): Wang Z, Malone MH, Thomenius MJ, Zhong F, Xu F, Distelhorst CW. Source: The Journal of Biological Chemistry. 2003 July 18; 278(29): 27053-8. Epub 2003 May 07. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12736248&dopt=Abstract
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DICE (dexamethasone, ifosfamide, cisplatin, etoposide) infusional chemotherapy for refractory or relapsed non-Hodgkin's lymphoma (NHL). Author(s): Coleman M, Leonard J, Shuster MW, Kaufman TP. Source: European Journal of Haematology. Supplementum. 2001 July; (64): 41-5. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11486401&dopt=Abstract
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Effect of polyunsaturated fatty acids on dexamethasone-induced gastric mucosal damage. Author(s): Manjari V, Das UN.
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Source: Prostaglandins, Leukotrienes, and Essential Fatty Acids. 2000 February; 62(2): 85-96. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10780873&dopt=Abstract •
Effects of a non-steroidal (ketorolac tromethamine) and a steroidal (dexamethasone) anti-inflammatory drug on refractive state and ocular growth. Author(s): Luu CD, Foo H, Crewther SG, Crewther DP. Source: Clinical & Experimental Ophthalmology. 2001 June; 29(3): 175-8. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11446463&dopt=Abstract
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Effects of chromium picolinate supplementation on insulin sensitivity, serum lipids, and body weight in dexamethasone-treated rats. Author(s): Kim DS, Kim TW, Park IK, Kang JS, Om AS. Source: Metabolism: Clinical and Experimental. 2002 May; 51(5): 589-94. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11979390&dopt=Abstract
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Effects of Genistein Isoflavone (4',5',7-Trihydroxyisoflavone) and Dexamethasone on Functional Characteristics of Spermatozoa. Author(s): Kumi-Diaka J, Townsend J. Source: Journal of Medicinal Food. 2001 Spring; 4(1): 39-47. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12639286&dopt=Abstract
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Endoscopic evaluation of the gastroduodenal mucosa to determine the safety of shortterm concurrent administration of meloxicam and dexamethasone in healthy dogs. Author(s): Boston SE, Moens NM, Kruth SA, Southorn EP. Source: Am J Vet Res. 2003 November; 64(11): 1369-75. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=14620772&dopt=Abstract
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Enteral glutamine supplementation and dexamethasone attenuate the local intestinal damage in rats with experimental necrotizing enterocolitis. Author(s): Dilsiz A, Ciftci I, Aktan TM, Gurbilek M, Karagozoglu E. Source: Pediatric Surgery International. 2003 October; 19(8): 578-82. Epub 2003 October 11. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=14556027&dopt=Abstract
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Fludarabine, mitoxantrone, dexamethasone (FND) compared with an alternating triple therapy (ATT) regimen in patients with stage IV indolent lymphoma. Author(s): Tsimberidou AM, McLaughlin P, Younes A, Rodriguez MA, Hagemeister FB, Sarris A, Romaguera J, Hess M, Smith TL, Yang Y, Ayala A, Preti A, Lee MS, Cabanillas F. Source: Blood. 2002 December 15; 100(13): 4351-7. Epub 2002 August 08. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12393618&dopt=Abstract
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Fractionated cyclophosphamide, vincristine, liposomal daunorubicin (daunoXome), and dexamethasone (hyperCVXD) regimen in Richter's syndrome. Author(s): Dabaja BS, O'Brien SM, Kantarjian HM, Cortes JE, Thomas DA, Albitar M, Schlette ES, Faderl S, Sarris A, Keating MJ, Giles FJ. Source: Leukemia & Lymphoma. 2001 July; 42(3): 329-37. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11699397&dopt=Abstract
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Fractionated cyclophosphamide, vincristine, liposomal daunorubicin, and dexamethasone plus rituximab and granulocyte-macrophage-colony stimulating factor (GM-CSF) alternating with methotrexate and cytarabine plus rituximab and GM-CSF in patients with Richter syndrome or fludarabine-refractory chronic lymphocytic leukemia. Author(s): Tsimberidou AM, Kantarjian HM, Cortes J, Thomas DA, Faderl S, GarciaManero G, Verstovsek S, Ferrajoli A, Wierda W, Alvarado Y, O'Brien SM, Albitar M, Keating MJ, Giles FJ. Source: Cancer. 2003 April 1; 97(7): 1711-20. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12655528&dopt=Abstract
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Galactoside-specific misletoe lectin modulates dexamethasone-induced apoptosis and glucocorticoid receptor level in Balb/c thymocytes. Author(s): Hajto T, Berki T, Palinkas L, Boldizsar F, Nagy G, Nemeth P. Source: In Vivo. 2003 March-April; 17(2): 163-7. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12792979&dopt=Abstract
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Granulocyte depletion and dexamethasone differentially modulate airways hyperreactivity, inflammation, mucus accumulation, and secretion induced by rmIL13 or antigen. Author(s): Singer M, Lefort J, Vargaftig BB. Source: American Journal of Respiratory Cell and Molecular Biology. 2002 January; 26(1): 74-84. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11751206&dopt=Abstract
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High dose of dexamethasone upregulates TCR/CD3-induced calcium response independent of TCR zeta chain expression in human T lymphocytes. Author(s): Nambiar MP, Enyedy EJ, Fisher CU, Warke VG, Tsokos GC. Source: Journal of Cellular Biochemistry. 2001 August 21-September 5; 83(3): 401-13. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11596109&dopt=Abstract
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High serum lactate dehydrogenase level predicts short survival after vincristinedoxorubicin-dexamethasone (VAD) salvage for refractory multiple myeloma. Author(s): Suguro M, Kanda Y, Yamamoto R, Chizuka A, Hamaki T, Matsuyama T, Takezako N, Miwa A, Togawa A. Source: American Journal of Hematology. 2000 October; 65(2): 132-5. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10996830&dopt=Abstract
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High-dose infusional ifosfamide, etoposide plus methylprednisolone followed by dexamethasone, high-dose ara-C and cisplatinum and autologous stem cell transplantation for refractory or relapsed aggressive non-Hodgkin's lymphoma. Author(s): Salar A, Martino R, Perea G, Ribera JM, Lopez-Guillermo A, Guardia R, Escoda L, Altes A, Sierra J, Montserrat E. Source: Haematologica. 2002 October; 87(10): 1028-35. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12368156&dopt=Abstract
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Hyperfractionated cyclophosphamide, vincristine, doxorubicin, and dexamethasone and highly active antiretroviral therapy for patients with acquired immunodeficiency syndrome-related Burkitt lymphoma/leukemia. Author(s): Cortes J, Thomas D, Rios A, Koller C, O'Brien S, Jeha S, Faderl S, Kantarjian H. Source: Cancer. 2002 March 1; 94(5): 1492-9. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11920506&dopt=Abstract
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Induction therapy consisting of alternating cycles of ranimustine, vincristine, melphalan, dexamethasone and interferon alpha (ROAD-IN) and a randomized comparison of interferon alpha maintenance in multiple myeloma: a co-operative study in Japan. Author(s): Wada M, Mizoguchi H, Kuriya SI, Taguchi H, Kawamura T, Maekawa I, Shimazaki C, Sato Y, Niho Y, Miyazaki T, Shibata A, Kitani T, Hamajima N, Ohno R. Source: British Journal of Haematology. 2000 June; 109(4): 805-14. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10929034&dopt=Abstract
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Intermediate doses of melphalan and dexamethasone are better than vincristine, adriamycin, and dexamethasone (VAD) and polychemotherapy for the treatment of primary plasma cell leukemia. Author(s): Vela-Ojeda J, Garcia-Ruiz Esparza MA, Rosas-Cabral A, Padilla-Gonzalez Y, Garcia-Chavez J, Tripp-Villanueva F, Sanchez-Cortes E, Ayala-Sanchez M, Garcia-Leon LD, Montiel-Cervantes L, Rubio-Borja ME. Source: Annals of Hematology. 2002 July; 81(7): 362-7. Epub 2002 June 25. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12185504&dopt=Abstract
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Outcomes of treatment of children and adolescents with recurrent non-Hodgkin's lymphoma and Hodgkin's disease with dexamethasone, etoposide, cisplatin, cytarabine, and l-asparaginase, maintenance chemotherapy, and transplantation: Children's Cancer Group Study CCG-5912. Author(s): Kobrinsky NL, Sposto R, Shah NR, Anderson JR, DeLaat C, Morse M, Warkentin P, Gilchrist GS, Cohen MD, Shina D, Meadows AT. Source: Journal of Clinical Oncology : Official Journal of the American Society of Clinical Oncology. 2001 May 1; 19(9): 2390-6. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11331317&dopt=Abstract
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Outpatient treatment of multiple myeloma with a combination of vincristine, Adriamycin and dexamethasone.
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Author(s): Egerer G, Hegenbart U, Salwender H, Haas R, Hahn U, Schmier JW, Ho AD, Goldschmidt H. Source: Supportive Care in Cancer : Official Journal of the Multinational Association of Supportive Care in Cancer. 2001 July; 9(5): 380-5. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11497393&dopt=Abstract •
Pain on intramuscular injection of bupivacaine, ropivacaine, with and without dexamethasone. Author(s): Krishnan SK, Benzon HT, Siddiqui T, Canlas B. Source: Regional Anesthesia and Pain Medicine. 2000 November-December; 25(6): 615-9. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11097670&dopt=Abstract
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Pegylated liposomal doxorubicin, vincristine, and reduced-dose dexamethasone as first-line therapy for multiple myeloma. Author(s): Hussein M. Source: Clinical Lymphoma. 2003 August; 4 Suppl 1: S18-22. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=14556672&dopt=Abstract
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Phase I study of hepatic arterial infusion of floxuridine and dexamethasone with systemic irinotecan for unresectable hepatic metastases from colorectal cancer. Author(s): Kemeny N, Gonen M, Sullivan D, Schwartz L, Benedetti F, Saltz L, Stockman J, Fong Y, Jarnagin W, Bertino J, Tong W, Paty P. Source: Journal of Clinical Oncology : Official Journal of the American Society of Clinical Oncology. 2001 May 15; 19(10): 2687-95. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11352961&dopt=Abstract
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Phase I/II study of hepatic arterial therapy with floxuridine and dexamethasone in combination with intravenous irinotecan as adjuvant treatment after resection of hepatic metastases from colorectal cancer. Author(s): Kemeny N, Jarnagin W, Gonen M, Stockman J, Blumgart L, Sperber D, Hummer A, Fong Y. Source: Journal of Clinical Oncology : Official Journal of the American Society of Clinical Oncology. 2003 September 1; 21(17): 3303-9. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12947066&dopt=Abstract
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Phase II trial of cyclophosphamide, vincristine, and dexamethasone in the treatment of androgen-independent prostate carcinoma. Author(s): Daliani DD, Assikis V, Tu SM, Papandreou CN, Pagliaro LC, Holtkamp T, Wang X, Thall PF, Logothetis CJ. Source: Cancer. 2003 February 1; 97(3): 561-7. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12548597&dopt=Abstract
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Potentiation of dexamethasone-, paclitaxel-, and Ad-p53-induced apoptosis by Bcl-2 antisense oligodeoxynucleotides in drug-resistant multiple myeloma cells. Author(s): Liu Q, Gazitt Y. Source: Blood. 2003 May 15; 101(10): 4105-14. Epub 2003 January 09. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12521996&dopt=Abstract
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Prospective randomized comparison of vincristine, doxorubicin and dexamethasone (VAD) administered as intravenous bolus injection and VAD with liposomal doxorubicin as first-line treatment in multiple myeloma. Author(s): Dimopoulos MA, Pouli A, Zervas K, Grigoraki V, Symeonidis A, Repoussis P, Mitsouli C, Papanastasiou C, Margaritis D, Tokmaktsis A, Katodritou I, Kokkini G, Terpos E, Vyniou N, Tzilianos M, Chatzivassili A, Kyrtsonis MC, Panayiotidis P, Maniatis A; Greek Myeloma Study Group. Source: Annals of Oncology : Official Journal of the European Society for Medical Oncology / Esmo. 2003 July; 14(7): 1039-44. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12853344&dopt=Abstract
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Pulmonary toxicity syndrome following CDEP (cyclophosphamide, dexamethasone, etoposide, cisplatin) chemotherapy. Author(s): Fassas A, Gojo I, Rapoport A, Cottler-Fox M, Meisenberg B, Papadimitriou JC, Tricot G. Source: Bone Marrow Transplantation. 2001 August; 28(4): 399-403. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11571514&dopt=Abstract
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Salivary cortisol levels and the cortisol response to dexamethasone before and after EMDR: a case report. Author(s): Heber R, Kellner M, Yehuda R. Source: Journal of Clinical Psychology. 2002 December; 58(12): 1521-30. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12455019&dopt=Abstract
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Short-term dietary conjugated linoleic acid supplementation does not enhance the recovery of immunodepleted dexamethasone-treated rats. Author(s): Turini ME, Boza JJ, Gueissaz N, Moennoz D, Montigon F, Vuichoud J, Gremaud G, Pouteau E, Piguet C, Perrin I, Verguet C, Finot PA, German B. Source: European Journal of Nutrition. 2003 June; 42(3): 171-9. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12811475&dopt=Abstract
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Sows' milk attenuates dexamethasone-induced reductions in liver docosahexaenoic acid. Author(s): Petryk L, Weiler HA. Source: Biology of the Neonate. 2002; 81(3): 188-95. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11937725&dopt=Abstract
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Successful treatment of multiple myeloma--associated amyloidosis by interferonalpha, dimethyl sulfoxide, and VAD (vincristine, adriamycin, and dexamethasone). Author(s): Ichida M, Imagawa S, Ohmine K, Komatsu N, Hatake K, Ozawa K, Miura Y. Source: International Journal of Hematology. 2000 December; 72(4): 491-3. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11197218&dopt=Abstract
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Synergistic effects of dexamethasone and genistein on the expression of Cdk inhibitor p21WAF1/CIP1 in human hepatocellular and colorectal carcinoma cells. Author(s): Park JH, Oh EJ, Choi YH, Kang CD, Kang HS, Kim DK, Kang KI, Yoo MA. Source: International Journal of Oncology. 2001 May; 18(5): 997-1002. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11295047&dopt=Abstract
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The combined dexamethasone-CRH test before and after repetitive transcranial magnetic stimulation (rTMS) in major depression. Author(s): Zwanzger P, Baghai TC, Padberg F, Ella R, Minov C, Mikhaiel P, Schule C, Thoma H, Rupprecht R. Source: Psychoneuroendocrinology. 2003 April; 28(3): 376-85. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12573303&dopt=Abstract
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Thioredoxin peroxidase-1 (peroxiredoxin-1) is increased in thioredoxin-1 transfected cells and results in enhanced protection against apoptosis caused by hydrogen peroxide but not by other agents including dexamethasone, etoposide, and doxorubicin. Author(s): Berggren MI, Husbeck B, Samulitis B, Baker AF, Gallegos A, Powis G. Source: Archives of Biochemistry and Biophysics. 2001 August 1; 392(1): 103-9. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11469800&dopt=Abstract
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Thromboembolic events in children with acute lymphoblastic leukemia (BFM protocols): prednisone versus dexamethasone administration. Author(s): Nowak-Gottl U, Ahlke E, Fleischhack G, Schwabe D, Schobess R, Schumann C, Junker R. Source: Blood. 2003 April 1; 101(7): 2529-33. Epub 2002 November 27. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12517808&dopt=Abstract
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Thymocytes selected for resistance to hydrogen peroxide show altered antioxidant enzyme profiles and resistance to dexamethasone-induced apoptosis. Author(s): Tome ME, Briehl MM. Source: Cell Death and Differentiation. 2001 September; 8(9): 953-61. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11526450&dopt=Abstract
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Treatment of plasma cell leukemia with vincristine, liposomal doxorubicin and dexamethasone. Author(s): Christou L, Hatzimichael E, Chaidos A, Tsiara S, Bourantas KL.
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Source: European Journal of Haematology. 2001 July; 67(1): 51-3. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11553267&dopt=Abstract •
Up-regulation of cochlear aquaporin-3 mRNA expression after intra-endolymphatic sac application of dexamethasone. Author(s): Kitahara T, Fukushima M, Uno Y, Mishiro Y, Kubo T. Source: Neurological Research. 2003 December; 25(8): 865-70. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=14669532&dopt=Abstract
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VEDex (vincristine, epirubicin dexamethasone): an effective and well tolerated palliative chemotherapy regimen for non-Hodgkin's lymphoma. Author(s): El Helw LM, Lorigan PC, Robinson MH, Coleman RE, Hancock BW. Source: International Journal of Oncology. 2000 April; 16(4): 777-82. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10717248&dopt=Abstract
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Very high dilutions of dexamethasone inhibit its pharmacological effects in vivo. Author(s): Bonamin LV, Martinho KS, Nina AL, Caviglia F, Do Rio RG. Source: Br Homeopath J. 2001 October; 90(4): 198-203. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11680804&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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WebMD®Health: http://my.webmd.com/drugs_and_herbs
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WholeHealthMD.com: http://www.wholehealthmd.com/reflib/0,1529,00.html
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Yahoo.com: http://dir.yahoo.com/Health/Alternative_Medicine/
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The following is a specific Web list relating to dexamethasone; please note that any particular subject below may indicate either a therapeutic use, or a contraindication (potential danger), and does not reflect an official recommendation: •
General Overview Asthma Source: Healthnotes, Inc.; www.healthnotes.com Hirsuitism Source: Integrative Medicine Communications; www.drkoop.com Systemic Lupus Erythematosus Source: Healthnotes, Inc.; www.healthnotes.com Tendinitis Source: Healthnotes, Inc.; www.healthnotes.com
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Herbs and Supplements Arctostaphylos Alternative names: Bearberry; Arctostaphylos uva-ursi (L.) Spreng. Source: Alternative Medicine Foundation, Inc.; www.amfoundation.org Arctostaphylos Uva Ursi Alternative names: Uva Ursi Source: Integrative Medicine Communications; www.drkoop.com Bearberry Alternative names: Uva Ursi Source: Integrative Medicine Communications; www.drkoop.com Beargrape Alternative names: Uva Ursi Source: Integrative Medicine Communications; www.drkoop.com Betula Alternative names: Birch; Betula sp. Source: Alternative Medicine Foundation, Inc.; www.amfoundation.org Cimicifuga Alternative names: Black Cohosh; Cimicifuga racemosa (NUTT.) Source: Alternative Medicine Foundation, Inc.; www.amfoundation.org Corticosteroids Source: Healthnotes, Inc.; www.healthnotes.com Curcuma Alternative names: Turmeric; Curcuma longa L. Source: Alternative Medicine Foundation, Inc.; www.amfoundation.org
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Dehydroepiandrosterone (DHEA) Source: Healthnotes, Inc.; www.healthnotes.com Garcinia Cambogia Alternative names: Citrin, Gambooge Source: Alternative Medicine Foundation, Inc.; www.amfoundation.org Glycyrrhiza Alternative names: Licorice; Glycyrrhiza glabra L. Source: Alternative Medicine Foundation, Inc.; www.amfoundation.org Hydrastis Alternative names: Goldenseal; Hydrastis canadensis L. Source: Alternative Medicine Foundation, Inc.; www.amfoundation.org Oral Corticosteroids Source: Healthnotes, Inc.; www.healthnotes.com Panax Alternative names: Ginseng; Panax ginseng Source: Alternative Medicine Foundation, Inc.; www.amfoundation.org Syzygium Clove Alternative names: Clove, Jamun; Syzygium sp. Source: Alternative Medicine Foundation, Inc.; www.amfoundation.org Tobradex Source: Healthnotes, Inc.; www.healthnotes.com Uva Ursi Alternative names: Arctostaphylos uva-ursi Source: Healthnotes, Inc.; www.healthnotes.com Uva Ursi Alternative names: Arctostaphylos uva ursi Source: Integrative Medicine Communications; www.drkoop.com
General References A good place to find general background information on CAM is the National Library of Medicine. It has prepared within the MEDLINEplus system an information topic page dedicated to complementary and alternative medicine. To access this page, go to the MEDLINEplus site at http://www.nlm.nih.gov/medlineplus/alternativemedicine.html. This Web site provides a general overview of various topics and can lead to a number of general sources.
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CHAPTER 4. DISSERTATIONS ON DEXAMETHASONE Overview In this chapter, we will give you a bibliography on recent dissertations relating to dexamethasone. We will also provide you with information on how to use the Internet to stay current on dissertations. IMPORTANT NOTE: When following the search strategy described below, you may discover non-medical dissertations that use the generic term “dexamethasone” (or a synonym) in their titles. To accurately reflect the results that you might find while conducting research on dexamethasone, we have not necessarily excluded non-medical dissertations in this bibliography.
Dissertations on Dexamethasone ProQuest Digital Dissertations, the largest archive of academic dissertations available, is located at the following Web address: http://wwwlib.umi.com/dissertations. From this archive, we have compiled the following list covering dissertations devoted to dexamethasone. You will see that the information provided includes the dissertation’s title, its author, and the institution with which the author is associated. The following covers recent dissertations found when using this search procedure: •
Dexamethasone Stimulation of Osteoprogenitor Differentiation in Adult Rat Bone Cell Populations Is Mediated in Part Through an Increased Response to Insulin-Like Growth Factors by Jia, Dan, PhD from University of Toronto (Canada), 2003, 172 pages http://wwwlib.umi.com/dissertations/fullcit/NQ78035
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Effects of Inflammation and Dexamethasone on Various Aspects of Glycoprotein Biosynthesis by Sarkar, Mohan Lal; PhD from Memorial University of Newfoundland (Canada), 1987 http://wwwlib.umi.com/dissertations/fullcit/NL45074
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Effects of Repeated Antenatal Dexamethasone (DEX) Exposure on HypothalamicPituitary-Adrenal (HPA) Function in Mature Adult Guinea Pigs (Cavis porcellus) by Banjanin, Sonja, MSC from University of Toronto (Canada), 2003, 156 pages http://wwwlib.umi.com/dissertations/fullcit/MQ78577
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Pulsatile Secretion of Gonadotropins and Ovarian Steriods during the Mid-luteal Phase in Cyclic Sows Treated with Dexamethasone by Frautschy, Sally Ann; PhD from University of Guelph (Canada), 1987 http://wwwlib.umi.com/dissertations/fullcit/NL37534
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REM Density, REM Latency and the Dexamethasone Suppression Test As Predictors of Treatment Response in Depressed Older Adults by Corbishley, Maureen Ann, PhD from The University of Arizona, 1987, 164 pages http://wwwlib.umi.com/dissertations/fullcit/8709889
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The Effects of Dexamethasone and Sunflower Oil on Adipose Tissue Development in Beef Steers by McCurdy, Matthew Pierce, MS from Michigan State University, 2003, 104 pages http://wwwlib.umi.com/dissertations/fullcit/1414672
Keeping Current Ask the medical librarian at your library if it has full and unlimited access to the ProQuest Digital Dissertations database. From the library, you should be able to do more complete searches via http://wwwlib.umi.com/dissertations.
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CHAPTER 5. CLINICAL TRIALS AND DEXAMETHASONE Overview In this chapter, we will show you how to keep informed of the latest clinical trials concerning dexamethasone.
Recent Trials on Dexamethasone The following is a list of recent trials dedicated to dexamethasone.8 Further information on a trial is available at the Web site indicated. •
A Study of PS-341 Given to Patients With Multiple Myeloma who Experienced Progressive Disease After Receiving Dexamethasone in M34101-039 Condition(s): Multiple Myeloma Study Status: This study is currently recruiting patients. Sponsor(s): Millennium Pharmaceuticals Purpose - Excerpt: The purpose of this study is to allow patients to receive VELCADE(tm) (bortezomib) for Injection who experienced progressive disease(PD) while receiving high-dose dexamethasone from the M34101-039 study. Phase(s): Phase III Study Type: Interventional Contact(s): see Web site below Web Site: http://clinicaltrials.gov/ct/show/NCT00063726
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Arsenic Trioxide and Dexamethasone in Treating Patients With Recurrent or Refractory Stage II or Stage III Multiple Myeloma Condition(s): refractory plasma cell neoplasm; stage II multiple myeloma; stage III multiple myeloma Study Status: This study is currently recruiting patients.
8
These are listed at www.ClinicalTrials.gov.
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Sponsor(s): Cell Therapeutics; National Cancer Institute (NCI) Purpose - Excerpt: RATIONALE: Drugs used in chemotherapy use different ways to stop cancer cells from dividing so they stop growing or die. Combining more than one drug may kill more cancer cells. PURPOSE: Phase II trial to study the effectiveness of combining arsenic trioxide and dexamethasone in treating patients who have recurrent or refractorystage II or stage III multiple myeloma. Phase(s): Phase II Study Type: Interventional Contact(s): see Web site below Web Site: http://clinicaltrials.gov/ct/show/NCT00017069 •
Calcitriol and Dexamethasone in Patients With Myelodysplastic Syndromes Condition(s): Myelodysplastic Syndromes Study Status: This study is currently recruiting patients. Sponsor(s): FDA Office of Orphan Products Development Purpose - Excerpt: This is a study to determine the response rate in patients with myelodysplastic syndromes treated with calcitriol and dexamethasone. Phase(s): Phase II Study Type: Interventional Contact(s): see Web site below Web Site: http://clinicaltrials.gov/ct/show/NCT00030069
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Calcitriol and Dexamethasone in Treating Patients With Prostate Cancer Who Have Undergone Surgery or Radiation Therapy Condition(s): adenocarcinoma of the prostate; recurrent prostate cancer Study Status: This study is currently recruiting patients. Sponsor(s): Roswell Park Cancer Institute; National Cancer Institute (NCI) Purpose - Excerpt: RATIONALE: Calcitriol may help tumor cells develop into normal cells. Dexamethasone may increase the effectiveness of calcitriol by making tumor cells more sensitive to the drug. PURPOSE: Phase II trial to study the effectiveness of combining calcitriol with dexamethasone in treating patients with prostate cancer who have undergone surgery or radiation therapy. Phase(s): Phase II Study Type: Interventional Contact(s): see Web site below Web Site: http://clinicaltrials.gov/ct/show/NCT00054522
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CC-5013 Plus Dexamethasone Versus Dexamethasone Alone in Previously Treated Subjects with Multiple Myeloma Condition(s): Multiple Myeloma Study Status: This study is currently recruiting patients. Sponsor(s): Celgene Corporation; PharmaNet
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Purpose - Excerpt: Randomized subjects will receive CC-5013 plus high-dose dexamethasone or identically appearing placebo to CC-5013 plus high-dose dexamethasone, in 4-week cycles. For each subject the study will consist of a treatment phase and a follow-up phase. Phase(s): Phase III Study Type: Interventional Contact(s): see Web site below Web Site: http://clinicaltrials.gov/ct/show/NCT00056160 •
Dexamethasone Compared With Prednisone During Induction Therapy and Methotrexate With or Without Leucovorin During Maintenance Therapy in Treating Patients With Newly Diagnosed High-Risk Acute Lymphoblastic Leukemia Condition(s): untreated childhood acute lymphoblastic leukemia; B-cell childhood acute lymphoblastic leukemia; untreated adult acute lymphoblastic leukemia; B-cell adult acute lymphoblastic leukemia Study Status: This study is currently recruiting patients. Sponsor(s): Children's Oncology Group; National Cancer Institute (NCI) Purpose - Excerpt: RATIONALE: Drugs used in chemotherapy, such as dexamethasone, prednisone, methotrexate, and leucovorin, work in different ways to stop cancer cells from dividing so they stop growing or die. Combining more than one drug may kill more cancer cells. It is not yet known which combination chemotherapyregimen is more effective in treating acute lymphoblastic leukemia. PURPOSE: Randomizedphase III trial to compare the effectiveness of dexamethasone with that of prednisone during induction therapy and methotrexate with or without leucovorin during maintenance therapy in treating patients who have newly diagnosed acute lymphoblastic leukemia. Phase(s): Phase III Study Type: Interventional Contact(s): see Web site below Web Site: http://clinicaltrials.gov/ct/show/NCT00075725
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Dexamethasone in Lupus Congenital Heart Block of Newborns Condition(s): Congenital heart block; dysfunction; Myocardial injury
Neonatal lupus;
Atrioventricular nodal
Study Status: This study is currently recruiting patients. Sponsor(s): National Institute of Arthritis and Musculoskeletal and Skin Diseases (NIAMS) Purpose - Excerpt: This study has two parts. The goal of the first part is to find out the usefulness of giving medications known as fluorinated steroids to pregnant women whose unborn children have a heart condition called congenital heart block (CHB). CHB occurs in some babies with neonatal lupus, a form of lupus that affects newborns but usually disappears by the time the infant is 3-6 months old. We will look at whether giving a steroid drug, such as dexamethasone, to pregnant women improves the heart function and general health of newborns who have autoantibody-associated CHB. This form of CHB is linked to the presence of certain blood proteins (antibodies) in the mother. Women enrolled must have antibodies to SSA/Ro and/or SSB/La and must be
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carrying a fetus with first, second, or third degree CHB diagnosed during gestation. It will be the decision of the physician and the mother as to whether a medication such as dexamethasone will be administered. The second part of the study will examine pregnant women who are at high risk for having babies with CHB to identify the earliest signs of heart problems in the unborn child that can be detected using ultrasound testing. We will follow 100 mothers considered at high risk for having a child with CHB by doing weekly echocardiograms (a noninvasive method that uses ultrasound to produce images of the heart) of the fetus from the 16th week of pregnancy. From week 28 to 34, echocardiograms will be performed every other week. Study Type: Observational Contact(s): see Web site below Web Site: http://clinicaltrials.gov/ct/show/NCT00007358 •
Floxuridine, Dexamethasone, and Irinotecan After Surgery in Treating Patients With Liver Metastases From Colorectal Cancer Condition(s): Colon Cancer; liver metastases; Rectal Cancer Study Status: This study is currently recruiting patients. Sponsor(s): Memorial Sloan-Kettering Cancer Center; National Cancer Institute (NCI) Purpose - Excerpt: RATIONALE: Drugs used in chemotherapy, such as floxuridine, dexamethasone, and irinotecan, use different ways to stop tumor cells from dividing so they stop growing or die. Hepatic arterial infusion uses a catheter to deliver chemotherapy directly to the liver. Combining more than one drug and giving them in different ways may kill any tumor cells remaining after surgery. PURPOSE: Phase II trial to study the effectiveness of irinotecan combined with hepatic arterial infusion with floxuridine and dexamethasone after surgery in treating patients who have liver metastases from colorectal cancer. Phase(s): Phase II Study Type: Interventional Contact(s): see Web site below Web Site: http://clinicaltrials.gov/ct/show/NCT00003753
•
Gemcitabine, Carboplatin, and Dexamethasone With or Without Rituximab in Treating Patients With Relapsed or Primary Refractory Lymphoma Condition(s): Hodgkin's lymphoma; adult T-cell leukemia and lymphoma; anaplastic large cell lymphoma; angioimmunoblastic T-cell lymphoma; Cutaneous T-Cell Lymphoma; Non-Hodgkin's Lymphoma Study Status: This study is currently recruiting patients. Sponsor(s): University of Washington; National Cancer Institute (NCI) Purpose - Excerpt: RATIONALE: Drugs used in chemotherapy, such as gemcitabine, carboplatin, and dexamethasone, use different ways to stop cancer cells from dividing so they stop growing or die. Monoclonal antibodies, such as rituximab, can locate cancer cells and either kill them or deliver cancer-killing substances to them without harming normal cells. Combining chemotherapy with monoclonal antibody therapy may kill more cancer cells. PURPOSE: Phase II trial to study the effectiveness of combining gemcitabine, carboplatin, and dexamethasone with or without rituximab in treating patients who have relapsed or primaryrefractorylymphoma.
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Phase(s): Phase II Study Type: Interventional Contact(s): see Web site below Web Site: http://clinicaltrials.gov/ct/show/NCT00072514 •
Methotrexate, Cyclophosphamide, and Etoposide Phosphate Given With Osmotic Blood-Brain Barrier Disruption Plus Dexamethasone and Cytarabine in Treating Patients With Primary CNS Lymphoma Condition(s): primary central nervous system lymphoma; intraocular lymphoma Study Status: This study is currently recruiting patients. Sponsor(s): Oregon Health and Science University; National Cancer Institute (NCI) Purpose - Excerpt: RATIONALE: Drugs used in chemotherapy, such as methotrexate, cyclophosphamide, etoposide phosphate, dexamethasone, and cytarabine, work in different ways to stop cancer cells from dividing so they stop growing or die. Osmotic blood-brain barrier disruption uses certain drugs to open the blood vessels around the brain and allow anticancer substances to be delivered directly to the brain. Giving methotrexate, cyclophosphamide, and etoposide phosphate with osmotic blood-brain barrier disruption plus dexamethasone and cytarabine may kill more cancer cells. PURPOSE: Phase II trial to study the effectiveness of giving methotrexate, cyclophosphamide, and etoposide phosphate with osmotic blood-brain barrier disruption plus dexamethasone and cytarabine in treating patients who have primary CNS lymphoma. Phase(s): Phase II Study Type: Interventional Contact(s): see Web site below Web Site: http://clinicaltrials.gov/ct/show/NCT00074178
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Methotrexate, Procarbazine, Lomustine, Dexamethasone, and Cytarabine in Treating Patients With Primary CNS Lymphoma Condition(s): intraocular lymphoma; primary central nervous system lymphoma Study Status: This study is currently recruiting patients. Sponsor(s): Oregon Health and Science University; National Cancer Institute (NCI) Purpose - Excerpt: RATIONALE: Drugs used in chemotherapy, such as methotrexate, procarbazine, lomustine, dexamethasone, and cytarabine, use different ways to stop cancer cells from dividing so they stop growing or die. Combining more than one drug may kill more cancer cells. PURPOSE: Phase II trial to study the effectiveness of combination chemotherapy in treating patients who have primary CNS lymphoma. Phase(s): Phase II Study Type: Interventional Contact(s): see Web site below Web Site: http://clinicaltrials.gov/ct/show/NCT00074191
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Ondansetron With or Without Dexamethasone to Prevent Vomiting in Patients Receiving Radiation Therapy to the Upper Abdomen Condition(s): Endocrine Cancer; female reproductive cancer; Gastrointestinal Cancer; nausea and vomiting; Quality of Life Study Status: This study is currently recruiting patients. Sponsor(s): National Cancer Institute of Canada Purpose - Excerpt: RATIONALE: Antiemetic drugs may help to reduce or prevent vomiting in patients treated with radiation therapy. It is not yet known if ondansetron is more effective with or without dexamethasone in preventing vomiting caused by radiation therapy. PURPOSE: Randomizedphase III trial to compare the effectiveness of ondansetron with or without dexamethasone in preventing vomiting in patients with cancer who are receiving radiation therapy to the upper abdomen. Phase(s): Phase III Study Type: Interventional Contact(s): see Web site below Web Site: http://clinicaltrials.gov/ct/show/NCT00016380
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Thalidomide, Dexamethasone, and Oblimersen in Treating Patients With Relapsed or Refractory Multiple Myeloma Condition(s): refractory plasma cell neoplasm Study Status: This study is currently recruiting patients. Sponsor(s): University of Maryland Greenebaum Cancer Center; National Cancer Institute (NCI) Purpose - Excerpt: RATIONALE: Thalidomide may slow the growth of cancer cells. Drugs used in chemotherapy use different ways to stop cancer cells from dividing so they stop growing or die. Oblimersen may increase the effectiveness of thalidomide and dexamethasone by making cancer cells more sensitive to the drugs. PURPOSE: Phase II trial to study the effectiveness of combining thalidomide and dexamethasone with oblimersen in treating patients who have relapsed or refractorymultiple myeloma. Phase(s): Phase II Study Type: Interventional Contact(s): see Web site below Web Site: http://clinicaltrials.gov/ct/show/NCT00049374
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Dexamethasone With or Without CC-5013 in Treating Patients With Newly Diagnosed Multiple Myeloma Condition(s): stage I multiple myeloma; stage II multiple myeloma; stage III multiple myeloma Study Status: This study is not yet open for patient recruitment. Sponsor(s): Southwest Oncology Group; National Cancer Institute (NCI) Purpose - Excerpt: RATIONALE: Drugs used in chemotherapy such as dexamethasone use different ways to stop cancer cells from dividing so they stop growing or die. CC5013 may stop the growth of multiple myeloma by stopping blood flow to the tumor. It is not yet known whether dexamethasone is more effective with or without CC-5013 in
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treating multiple myeloma. PURPOSE: Randomizedphase III trial to compare the effectiveness of dexamethasone with or without CC-5013 in treating patients who have newly diagnosed multiple myeloma. Phase(s): Phase III Study Type: Interventional Contact(s): see Web site below Web Site: http://clinicaltrials.gov/ct/show/NCT00064038 •
Epoetin alfa With or Without Dexamethasone in Treating Fatigue and Anemia in Patients With Hormone-Refractory Prostate Cancer Condition(s): recurrent prostate cancer; Anemia; Fatigue Study Status: This study is not yet open for patient recruitment. Sponsor(s): Eastern Cooperative Oncology Group; National Cancer Institute (NCI) Purpose - Excerpt: RATIONALE: Epoetin alfa may stimulate red blood cell production and may help improve cancer-related anemia and fatigue. Steroid therapy with dexamethasone may increase the effectiveness of epoetin alfa. It is not yet known if epoetin alfa is more effective with or without dexamethasone in treating anemia-related fatigue in patients with prostate cancer. PURPOSE: Randomizedphase III trial to compare the effectiveness of epoetin alfa with or without dexamethasone in treating anemia-related fatigue in patients who have prostate cancer that is refractory to treatment with hormone therapy. Phase(s): Phase III Study Type: Interventional Contact(s): see Web site below Web Site: http://clinicaltrials.gov/ct/show/NCT00060398
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 “dexamethasone” (or synonyms). While ClinicalTrials.gov is the most comprehensive listing of NIH-supported clinical trials available, not all trials are in the database. The database is updated regularly, so clinical trials are continually being added. The following is a list of specialty databases affiliated with the National Institutes of Health that offer additional information on trials: •
For clinical studies at the Warren Grant Magnuson Clinical Center located in Bethesda, Maryland, visit their Web site: http://clinicalstudies.info.nih.gov/
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For clinical studies conducted at the Bayview Campus in Baltimore, Maryland, visit their Web site: http://www.jhbmc.jhu.edu/studies/index.html
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For cancer trials, visit the National Cancer Institute: http://cancertrials.nci.nih.gov/
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For eye-related trials, visit and search the Web page of the National Eye Institute: http://www.nei.nih.gov/neitrials/index.htm
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For heart, lung and blood trials, visit the Web page of the National Heart, Lung and Blood Institute: http://www.nhlbi.nih.gov/studies/index.htm
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For trials on aging, visit and search the Web site of the National Institute on Aging: http://www.grc.nia.nih.gov/studies/index.htm
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For rare diseases, visit and search the Web site sponsored by the Office of Rare Diseases: http://ord.aspensys.com/asp/resources/rsch_trials.asp
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For alcoholism, visit the National Institute on Alcohol Abuse and Alcoholism: http://www.niaaa.nih.gov/intramural/Web_dicbr_hp/particip.htm
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For trials on infectious, immune, and allergic diseases, visit the site of the National Institute of Allergy and Infectious Diseases: http://www.niaid.nih.gov/clintrials/
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For trials on arthritis, musculoskeletal and skin diseases, visit newly revised site of the National Institute of Arthritis and Musculoskeletal and Skin Diseases of the National Institutes of Health: http://www.niams.nih.gov/hi/studies/index.htm
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For hearing-related trials, visit the National Institute on Deafness and Other Communication Disorders: http://www.nidcd.nih.gov/health/clinical/index.htm
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For trials on diseases of the digestive system and kidneys, and diabetes, visit the National Institute of Diabetes and Digestive and Kidney Diseases: http://www.niddk.nih.gov/patient/patient.htm
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For drug abuse trials, visit and search the Web site sponsored by the National Institute on Drug Abuse: http://www.nida.nih.gov/CTN/Index.htm
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For trials on mental disorders, visit and search the Web site of the National Institute of Mental Health: http://www.nimh.nih.gov/studies/index.cfm
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For trials on neurological disorders and stroke, visit and search the Web site sponsored by the National Institute of Neurological Disorders and Stroke of the NIH: http://www.ninds.nih.gov/funding/funding_opportunities.htm#Clinical_Trials
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CHAPTER 6. PATENTS ON DEXAMETHASONE 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 “dexamethasone” (or a synonym) in their titles. To accurately reflect the results that you might find while conducting research on dexamethasone, we have not necessarily excluded non-medical patents in this bibliography.
Patents on Dexamethasone By performing a patent search focusing on dexamethasone, 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 dexamethasone: •
Anti-emetic composition Inventor(s): Naeger; David M. (8 Gladiola Center, Newtown, PA 18940-4224) Assignee(s): None Reported Patent Number: 5,661,142 Date filed: April 17, 1996 Abstract: The invention relates to an anti-emetic composition that comprises dexamethasone (DEX), metoclopramide (MTC) and an antihistamine or an anticholinergic agent. In a particular embodiment, a composition containing DEX:MTC:diphenhydramine in a relative weight ratio of about 1:1:2.5, respectively, is found to be effective in providing relief from the discomfort caused by symptoms of both vomiting and nausea in all patients receiving the composition. Alternatively, an effective composition may contain DEX:MTC:scopolamine in a relative weight ratio of about 1:1:0.025, respectively. Other effective compositions and methods of their use are also disclosed. Excerpt(s): The present invention relates to both a therapeutic composition comprising a combination of antiemetic drugs and to a method for treating emesis, including nausea. Nausea and vomiting can follow the administration of many drugs, particularly anticancer or chemotherapeutic agents. The symptoms also often accompany infectious and non-infectious gastrointestinal disorders. The initial manifestations of the vomiting response often involves nausea, in which gastric tone is reduced, gastric peristalsis is reduced or absent and the tone of the duodenum and upper jejunum is increased, such that their contents reflux. Ultimately, the upper portion of the stomach relaxes while the pylorus constricts, and the coordinated contraction of the diaphragm and abdominal muscles leads to expulsion of gastric contents. Goodman and Gilman's The Pharmacological Basis of Therapeutics, 8th Edition, Pergamon Press, New York, pp. 925928 (1990). Web site: http://www.delphion.com/details?pn=US05661142__
•
Anti-inflammatory compounds for ophthalmic use Inventor(s): Boltralik; John J. (Ft. Worth, TX) Assignee(s): Alcon Laboratories, Inc. (fort Worth, Tx) Patent Number: 5,223,493 Date filed: March 17, 1992 Abstract: Anti-inflammatory compounds, a method of treating inflamed ocular tissue and compositions of these compounds are described. The compounds are derivatives and analogues of known steroid compounds (e.g., dexamethasone) and are advantageously characterized in that they do not cause any significant increase in intraocular pressure during chronic use. Excerpt(s): The present invention relates to novel derivatives of known antiinflammatory steroids, processes useful for their preparation, and use of a these novel derivatives in the treatment of ophthalmic inflammatory disorders. More particularly,
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this invention relates to the treatment of ophthalmic inflammatory disorders with novel derivatives of known anti-inflammatory steroids, wherein the novel derivatives do not cause any significant increase in intraocular pressure. Anti-inflammatory steroids, such as hydrocortisone, prednisolone, dexamethasone, and fluorometholone, are very useful in controlling a wide range of ophthalmic inflammatory conditions. This usefulness may be somewhat negated due to a steroid-induced side effect associated with the chronic use of these compounds. This side effect may be manifested by a rise in intraocular pressure (IOP) in steroid-sensitive patients (steroid-responders), an increase in IOP in glaucoma sensitive patients, or an exacerbation of IOP in patients suffering from frank primary open angle glaucoma. Further discussion of this side effect is presented in an article by Phillips, et al., The Lancet, 767-768 (Apr. 7, 1984). The above-described manifestations can generally be tolerated in most patients over a relatively short treatment period (i.e., four to six weeks, or less); however, the increase in IOP caused by these compounds is generally unacceptable over extended periods of treatment (i.e., one to twelve months, or more), especially in individuals subject to chronic eye inflammation. The increased intraocular pressure associated with the short term use of these s compounds may also be unacceptable in certain patients, such as patients already suffering from an elevated IOP (e.g., glaucoma patients). A need therefore exists for an effective means of treating inflamed ocular tissue without risk of elevating IOP. The present invention is directed to satisfying this need. Web site: http://www.delphion.com/details?pn=US05223493__ •
Anti-inflammatory-agent-loaded catheter and method for preventing tissue fibrosis Inventor(s): Baudino; Michael D. (Coon Rapids, MN) Assignee(s): Medtronic, Inc. (minneapolis, Mn) Patent Number: 6,110,155 Date filed: April 30, 1996 Abstract: At least a portion of a catheter which is intended to be in contact with bodily tissue for more than a nominal period of time is loaded with an anti-inflammatory agent such as dexamethasone sodium phosphate. The direct loading or compounding of the catheter with the agent resists inflammation and encapsulation of the catheter as a result of the tissue's natural foreign-body response. The anti-inflammatory agent can be provided as a coating or bonded on the outside of the catheter or can be integrally compounded into the body of the catheter. Excerpt(s): This invention relates to catheters for the conduction of fluids to and from internal bodily organs, and more particularly, to a catheter which is loaded or impregnated with an anti-inflammatory agent to obviate or abate the human foreignbody response to the implanted catheter. Catheters have long found innumerable applications in a wide variety of medical procedures, including both therapeutic and diagnostic procedures. Catheters are eminently useful, for example, as passageways for delivery of fluids to the patient and removal of fluids from the patient. They are thus routinely employed to conduct fluids containing medicaments from a source thereof directly to the tissue of an internal organ. Such catheters may be placed in the parenchyma of an organ such as the brain or pancreas for direct delivery of medicaments to the parenchyma, usually by way of a bore formed in the tissue of the parenchyma by incision, perforation or puncture. The human body spontaneously rejects or encapsulates a foreign body which has been introduced into the body or a specific bodily organ. Such phenomena in connection with implants are described with
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particularity in U.S. Pat. No. 5,219,361, issued Jun. 15, 1993 to A. F. von Recum et al. In some cases, encapsulation will impede or halt infusion through blockage of the catheter. In essence, the body's own natural defense systems frustrate the potentially beneficial procedure of directly removing or supplying fluid to the tissue. Web site: http://www.delphion.com/details?pn=US06110155__ •
Coated implantable medical device Inventor(s): Fearnot; Neal E. (West Lafayette, IN), Kozma; Thomas G. (West Lafayette, IN), Ragheb; Anthony O. (West Lafayette, IN), Voorhees; William D. (West Lafayette, IN) Assignee(s): Med Institute, Inc. (west Lafayette, In) Patent Number: 5,609,629 Date filed: June 7, 1995 Abstract: A coated implantable medical device 10 includes a structure 12 adapted for introduction into the vascular system, esophagus, trachea, colon, biliary tract, or urinary tract; at least one layer 18 of a bioactive material positioned over the structure 12; and at least one porous layer 20 positioned over the bioactive material layer 18. Preferably, the structure 12 is a coronary stent, and the bioactive material is at least one of heparin, dexamethasone or a dexamethasone derivative. The device 10 includes layers 18 and 22 of heparin and dexamethasone, the layer 22 of dexamethasone being positioned above the layer 18 of heparin. The layers of bioactive material also can be individual materials or a combination of different materials. Unexpectedly, the more soluble heparin markedly promotes the release of the less soluble dexamethasone above it. The porous layer 20 is composed of a polymer applied by vapor or plasma deposition and provides a controlled release of the bioactive material. It is particularly preferred that the polymer is a polyimide, parylene or a parylene derivative, which is deposited without solvents, heat or catalysts, merely by condensation of a monomer vapor. Excerpt(s): This invention relates generally to human and veterinary medical devices, and more particularly to devices incorporating drugs or bioactive agents. It has become common to treat a variety of medical conditions by introducing an implantable medical device partly or completely into the esophagus, trachea, colon, biliary tract, urinary tract, vascular system or other location within a human or veterinary patient. For example, many treatments of the vascular system entail the introduction of a device such as a stent, a catheter, a balloon, a wire guide, a cannula or the like. However, when such a device is introduced into and manipulated through the vascular system, the blood vessel walls can be disturbed or injured. Clot formation or thrombosis often results at the injured site, causing stenosis (closure) of the blood vessel. Moreover, if the medical device is left within the patient for an extended period of time, thrombus often forms on the device itself, again causing stenosis. As a result, the patient is placed at risk of a variety of complications, including heart attack, pulmonary embolism, and stroke. Thus, the use of such a medical device can entail the risk of precisely the problems that its use was intended to ameliorate. Another way in which blood vessels undergo stenosis is through disease. Probably the most common disease causing stenosis of blood vessels is atherosclerosis. Atherosclerosis is a condition which commonly affects the coronary arteries, the aorta; the iliofemoral arteries and the carotid arteries. Atherosclerotic plaques of lipids, fibroblasts, and fibrin proliferate and cause obstruction of an artery or arteries. As the obstruction increases, a critical level of stenosis is reached, to the point where the flow of blood past the obstruction is insufficient to meet the
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metabolic needs of the tissue distal to (downstream of) the obstruction. The result is ischemia. Web site: http://www.delphion.com/details?pn=US05609629__ •
Combination of tobramycin and dexamethasone for topical ophthalmic use Inventor(s): Cagle; Gerald D. (Fort Worth, TX), McDonald; Thomas O. (Fort Worth, TX), Rosenthal; Allan L. (Fort Worth, TX) Assignee(s): Alcon Laboratories, Inc. (fort Worth, Tx) Patent Number: 5,149,694 Date filed: November 22, 1989 Abstract: Disclosed are pharmaceutical compositions comprising tobramycin and dexamethasone for topical ophthalmic delivery and a method of treatment comprising administering said composition when indicated for infection and control of inflammatory response for optimal wound healing and normalization of the eye. Excerpt(s): This invention relates to the topical ophthalmic use of antibiotics in combination with anti-inflammatory steroids when indicated for treatment of ophthalmic infections and attendant inflammation. Such combinations or formulations are available in the ophthalmic art. However, there are concerns and expressed reservations in the ophthalmic community about the safety and efficacy of such prior art combinations. There is, moreover a long felt need for an effective and safe topical ophthalmic pharmaceutical composition of a potent steroid and a broad spectrum antibiotic which, when administered to the eye when indicated for bacterial infection or as a prophylactic after ophthalmic trauma and injury, will not, as a possible expression of the steroid component, inhibit the activity of the antibiotic or interfere width normal wound healing, but at the same time will control inflammation. Unexpectedly it has been discovered that the broad spectrum aminoglycoside antibiotic tobramycin in combination with the potent steroid dexamethasone meets these criteria. Other ingredients which may be desirable to use in the ophthalmic preparations of the present invention include preservatives, co-solvents and viscosity builder agents. Ophthalmic products are typically packaged in multidose form. Preservatives are thus required to prevent microbial contamination during use. Suitable preservatives include: benzalkonium chloride, thimerosal, chlorobutanol, methyl paraben, propyl paraben, phenylethyl alcohol, edetate disodium sorbic acid, Onamer M, or other agents known to those skilled in the art. Typically such preservatives are employed at a level of from 0.001% to 1.0% by weight. Web site: http://www.delphion.com/details?pn=US05149694__
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Control of DNA sequence transcription Inventor(s): Brinster; Ralph L. (Gladwyne, PA), Palmiter; Richard D. (Seattle, WA) Assignee(s): University Patents, Inc. (westport, Ct) Patent Number: 4,579,821 Date filed: November 23, 1981 Abstract: The transcription of DNA sequences in living cells is subjected to external regulation by incorporation of promoter/regulator DNA sequences responsive to metals
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and/or steroids. More particularly, regulation of the transcription of selected exogenous DNA sequences incorporated into eukaryotic host cells is facilitated by operative association (e.g., fusion) of the selected sequence to a promoter/regulator DNA sequence which is positively or negatively responsive to environmental variation in the concentration of heavy metal ions and/or steroid hormones. As an example, a structural gene for thymidine kinase from herpes simplex virus, fused to the promoter/regulator DNA sequence of a mouse metallothionein-I gene and incorporated on a suitable DNA plasmid vector, is introduced into mouse embryos and stably incorporated therein. Gene expression in differentiated cells of adult mice resulting from the embryos is subsequently regulatable by administration of heavy metals such as cadmium or steroid hormones such as the glucocorticoid, dexamethasone. Excerpt(s): The present invention relates generally to manipulation of genetic materials and, more particularly, to methods and materials useful in subjecting the transcription of particular DNA sequences to selective regulation by external control. Most simply put, the programming function of genetic materials is generally effected through a process whereby DNA nucleotide sequences (genes) are "transcribed" into relatively unstable messenger RNA ("mRNA") polymers which, in turn, serve as templates for formation of structural, regulatory and catalytic proteins from amino acids. Protein synthesis is thus the ultimate form of "expression" of the programmed genetic message provided by the DNA sequence of a gene. Certain DNA sequences which usually "precede" a gene in a DNA polymer provide a site for initiation of the transcription into mRNA. These are referred to as "promoter" sequences. Other DNA sequences, also usually "upstream" of a gene in a given DNA polymer, bind proteins that determine the frequency (or rate) of transcription initiation. These other sequences are referred to as "regulator" sequences. Thus, sequences which precede a selected gene (or series of genes) in a functional DNA polymer and which operate to determine whether the transcription (and eventual expression) of a gene will take place are collectively referred to as "promoter/regulator" DNA sequences. Web site: http://www.delphion.com/details?pn=US04579821__ •
Double chamber tissue expander Inventor(s): Rosenberg; Paul H. (1600 Parker Ave. #27D, Fort Lee, NJ 10021) Assignee(s): None Reported Patent Number: 5,630,843 Date filed: June 30, 1994 Abstract: A tissue expansion device for subcutaneous implantation in a patient consisting of an implantable expandable bladder prepared from a porous material which defines an infusion solution chamber, and an inner bladder disposed within the outer bladder prepared from an expandable non-porous material which defines an expansion solution chamber. Liquid transport means are provided for introducing and removing an infusion solution into and out of the infusion solution chamber, and fluid transport means are provided for introducing and removing an expansion fluid into and out of the expansion solution chamber. Following implantation of the tissue expansion device subcutaneously, expansion fluid can be introduced into the expansion chamber by use of the fluid transport means causing the inner bladder to expand. The expansion of the inner bladder exerts pressure on the infusion chamber, which contains infusion solution introduced through the liquid transport means. The infusion solution passes through the pores of the expandable porous material into the tissue surrounding and
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contacting the expansile porous wall of the implanted tissue expansion device. The outer bladder also expands, due primarily to expansion of the inner bladder and to introduction of infusion solution. The infusion solution can contain agents to facilitate the expansion process, such as hyaluronidase, lidocaine, epidermal growth factor, or dexamethasone, or any combination thereof. Excerpt(s): The present invention relates to a device for the expansion of tissue, in particular, to an implantable tissue expander which provides for a liquid solution to diffuse into the subcutaneous tissue in contact with or proximity to the expansile (or expansible) surface of the implanted device. In the field of reconstructive surgery, tissue expanders play an important role. Mechanical tissue expansion is a means to increase the dimensions of tissue. The technique is commonly used in surgery involving the implantation of permanent prosthetics, such as breast reconstruction, and reconstructive surgery in which additional skin is required, such as burn reconstruction. Tissue expansion for cosmetic or reconstructive surgery has two components: dissection of the skin and subdermal elements from the underlying tissue, to create a cavity, and expansion of an expander device placed in the cavity to stretch the surrounding tissues, particularly the skin. The dissection process may continue after implantation of an expander, thus recruiting additional tissue to stretch in response to the force of the expander. Web site: http://www.delphion.com/details?pn=US05630843__ •
Evaluative means for detecting inflammatory reactivity Inventor(s): Chrousos; George P. (Bethesda, MD), Gold; Philip W. (Washington, DC), Sternberg; Esther M. (Chevy Chase, MD), Wilder; Ronald L. (Rockville, MD) Assignee(s): The United States of America AS Represented by the of the Department of (washington, Dc) Patent Number: 5,006,330 Date filed: November 30, 1988 Abstract: Inbred Lewis (LEW/N) female rats develop an arthritis in response to Group A streptococcal cell wall peptidoglycanpolysaccharide (SCW) which mimics human rheumatoid arthritis. Histocompatible Fischer (F344/N) rats, on the other hand, do not develop arthritis in response to the same SCW stimulus. To evaluate this difference in inflammatory reactivity between the two strains, the function of the hypothalamicpituitary-adrenal axis and its ability to modulate the development of the inflammatory response was studied. It has been found that, in contrast to F344/N rats, LEW/N rats had markedly impaired plasma ACTH and corticosterone responses to SCW, recombinant human Interleukin-1 alpha (IL-1 alpha), the serotonin agonist, quipazine, and synthetic rat corticotropin-releasing hormone (CRH). In addition, LEW/N rats compared to F344/N rats had smaller adrenal glands and larger thymuses. Treatment of LEW/N rats with replacement doses of dexamethasone decreased the severity of their SCW-induced arthritis. Conversely, treatment of F344/N rats with the glucocorticoid receptor antagonist, RU 486, or the serotonin (5-HT.sub.2) antagonist, LY53857, was associated with development of severe inflammatory disease, including arthritis, in response to SCW. These findings support the concept that susceptibility of LEW/N rats to SCW arthritis is related to abnormal hypothalamic-pituitary-adrenal (HPA) axis responsiveness to inflammatory and other stress mediators and that resistance of F344/N rats to SCW arthritis is regulated by an intact HPA axis-immune system feedback loop.
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Excerpt(s): The present invention relates to a diagnostic test for testing the susceptibility of individuals to inflammatory diseases such as rheumatoid arthritis. It is an object of the present invention to provide a method for testing mammals for susceptibility to inflammatory diseases. In its broadest aspect, the method comprises the steps of administering to a mammal a compound which is effective in stimulating the hypothalamic-pituitary-adrenal (HPA) axis and measuring the level of hormones secreted by the pituitary and adrenal glands of the mammal. In a more specific aspect, the method comprises the steps of administering to a mammal a compound selected from the group consisting of cytokines, cell growth factors, corticotropin releasing hormone (CRH), biogenic amines, agonists of biogenic amines, antagonists of biogenic amines, analogues of biogenic amines, monoamine oxidase inhibitors and biogenic amine uptake inhibitors or glucocorticoid receptor antagonists and measuring the level of glucocorticoids or adrenocorticotropic hormone (ACTH) in the blood plasma of the mammal. The substance which is administered should not be the same as the material which is measured. The invention is useful as a model in the study of the mammalian autoimmune diseases. Laboratory animals which may serve as a good model in studying human systems include rats, mice, guinea pigs, rabbits and chickens. However, an ultimate objective of this invention is to provide a method for diagnosing the susceptibility of humans to inflammatory diseases. Web site: http://www.delphion.com/details?pn=US05006330__ •
Glucocorticoid receptor agonist and decreased PP5 Inventor(s): Honkanen; Richard E. (Mobile, AL) Assignee(s): South Alabama Medical Science Foundation (mobile, Al) Patent Number: 6,235,891 Date filed: March 31, 1999 Abstract: A composition comprises a glucocorticoid receptor agonist and a compound which decreases levels of active human serine/threonine protein phosphatase 5 protein in cells. The glucocorticoid receptor agonist is dexamethasone and the compound is an antisense oligonucleotide of about 8 to 50 nucleotides in length which is targeted to a nucleic acid encoding human serine/threonine protein phosphatase 5. The composition is useful in a method of enhancing glucocorticoid activity, and in a method of enhancing the inhibition of hyperproliferation of cells where the inhibition is by contacting the cells with a compound which decreases levels of active human serine/threonine protein phosphatase 5 protein in cells. The compound is thus useful to enhance glucocorticoid therapy and to enhance inhibition of hyperproliferation relating to PP5. Excerpt(s): This invention relates generally to compositions and methods for enhancing glucocorticoid therapy and for enhancing the inhibition of hyperproliferation of cells, and more particularly to a composition comprising a glucocorticoid receptor agonist and a compound which decreases levels of active human serine/threonine protein phosphatase 5 in cells. Throughout this application various publications are referenced, many in parenthesis. Full citations for each of these publications are provided at the end of the Detailed Description. The disclosures of each of these publications in their entireties are hereby incorporated by reference in this application. Abnormal proliferative or hyperproliferative conditions include hypoproliferative disorders such as cancer, tumors and hyperplasias, including smooth muscle cell proliferation in the blood vessels (such as stenosis or restenosis following angiopathy). In these conditions, a means to control or inhibit (decrease) hyperproliferation is desirable. Many types of
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cellular mechanisms/molecules have been or could be associated with regulation of cellular proliferation. For example, the reversible phosphorylation of proteins on serine and threonine residues is a major intracellular control mechanism that regulates cell proliferation. The phosphorylation state of a protein is controlled by kinases, which phosphorylate proteins, and phosphatases, which dephosphorylate proteins. A number of families and types of protein phosphatases exist, including tyrosine phosphatases and serine/threonine protein phosphatases (PPs). An increase in expression of certain PPs has been described in several tumor types. Therefore, one could speculate that inhibitors of PP expression may have an effect on tumors (such as an anti-proliferative effect). Web site: http://www.delphion.com/details?pn=US06235891__ •
Immortalized human colon epithelial cell line Inventor(s): Blum; Stephanie (Lausanne, CH), Pfeifer; Andrea (St-Legier, CH), Tromvoukis; Yvonne (Effretikon, CH) Assignee(s): Nestec S.a. (vevey, Ch) Patent Number: 6,395,542 Date filed: June 14, 2000 Abstract: Human epithelial colon immortalized cell line, which does not express tumour markers, which expresses metabolic markers specific for the non-immortalized human epithelial cells and metabolic differentiation markers specific for the non-immortalized epithelial cells of the human colon, and which is capable of adhering in vitro to the strain of lactic acid bacterium CNCM-1225. Serum-free culture medium characterized in that it comprises trace elements, vitamins consisting of vitamin C and retinoic acid, and hormones consisting of triiodothyronine, dexamethasone, hydrocortisone, bovine pituary gland extract, insulin, EGF and transferrin. Process for the immortalization of epithelial cells of the human colon, in which a culture of primary epithelial cells derived from the human colon is prepared, the culture is infected with a recombinant virus, the immortalized cells are cultured in the serum-free culture medium according to the invention. Process for identifying the mutagenic, toxic or beneficial effect of an agent on the metabolism of the cells of the intestinal tract, in which (1) an agent suspected of being a mutagenic, toxic or beneficial agent for the metabolism of the cells of the intestinal tract is reacted, cultured or brought into contact with a culture comprising a cell line according to the invention, and (2) the effects of the said agent on the said cell line are determined or measured. Use of the cells according to the invention as an active pharmaceutical agent. Excerpt(s): The subject of the present invention is a new human epithelial colon immortalized cell line, a method for obtaining this line, as well as any use of this line, especially in processes for the identification of mutagenic, toxic or beneficial agents for the metabolism of the cells of the intestinal tract. For many years, efforts have been made to develop human cell lines adapted to the study of human diseases, such as infections, inflammations or cancers, for example. Among the cells often involved in the onset of diseases, there are the epithelial cells, in particular the epithelial cells of the intestinal tract which are sensitive to the surroundings of the human body, and especially to the conditions of its diet. Finally, the epithelial cells of the human colon also differ from other human epithelial cells in the expression of compounds or structures found mainly in the epithelial cells of the human intestine, such as, for example, surface villosities (Friedrich et al., Bioassays, 12, No. 9, 403-408, 1990), sucrose isomaltase (Gibson et al., Gut, 35, 791-797, 1994; Paul et al., Am. Pysiol. Soc., C266-C278,
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1993), certain class II major histocompatibility antigens (Mayer et al., Gastroenterology, 100, 3-12, 1991), and dipeptidylpeptidase IV (DPPIV; Hauri et al., J. Cell. Biol., 101, 836851, 1985). Web site: http://www.delphion.com/details?pn=US06395542__ •
Injection viral treatment Inventor(s): Fabunan; Ruben G. (329 N. Vendome St., Los Angeles, CA 90026) Assignee(s): None Reported Patent Number: 6,172,053 Date filed: September 13, 1999 Abstract: The present invention relates to a therapeutic composition and formulation for the treatment of viral diseases such as, Dengue fever and influenza. More particularly, to therapeutic preparation comprising substantially water soluble, local anesthetic of the ester type, procaine hydrochloride and a water soluble glucocorticoid, dexamethasone sodium phosphate. Excerpt(s): The present invention relates to a therapeutic composition for the treatment of viral infections and a method of administration thereof. More particularly, the invention relates to a therapeutic composition including a substantially water soluble local anesthetic of the ester type injectable and a water soluble glucocorticoid injectable, and to the method of administering said composition to an infected patient. In both Third-world and developing countries and also in developed countries, there is a prevalent need for an economical yet effective viral treatment to both ease human suffering and save lives. The present invention relates directly to both of these needs since it has been compassionately used to treat and/or cure a number of known pathogenic viruses, including but not limited to human immunodeficiency virus (HIV) causing acquired immunodeficiency syndrome (AIDS), Dengue fever virus, influenza virus, rhinovirus causing common colds, herpes zoster virus, mumps virus, measles virus, hepatitis virus, conjunctivitis virus, rabies virus, chickenpox virus and other viruses found in equatorial environments common to Third-World and developing countries but also found with increasing prevalence in industrialized nations. To the best of the inventor's knowledge, in medical textbooks or in current clinical practice, there is no treatment, cure or vaccine for the Dengue fever virus. This invention comes about after many years of field testing, and now over two years of clinical studies at the Fabunan Medical Clinic located in the province of Zambales, the Philippines in Southeast Asia. Each known virus that has been treated with this composition has shown a remarkably significant improvement and/or curative result with no serious side effects. Routine cases were clinically diagnosed and then treatment began. A patient usually improved and recovered within seventy two hours but, sometimes, more time was needed. Web site: http://www.delphion.com/details?pn=US06172053__
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Issue repair and regeneration through the use of platelet derived growth factor (PDGF) in combination with dexamethasone Inventor(s): Rutherford; Robert B. (Farmington, CT) Assignee(s): Creative Biomolecules, Inc. (hopkinton, Ma) Patent Number: 5,149,691 Date filed: March 12, 1991 Abstract: Disclosed is a method for the regeneration of tissue, the treatment of external wounds and the treatment of periodontal disease comprised of applying to the afflicted tissue a pharmaceutically effective amount of a composition comprised of plateletderived growth factor and dexamethasone. Excerpt(s): The present invention lies in the field of tissue regeneration and wound regeneration and wound repair. Polypeptide growth factors are a class of natural biological mediators that regulate the proliferation, differentiation, motility and matrix synthesis of nearly all cell types. These properties, demonstrable in vitro, have led to the proposal that such factors play important roles in soft and hard tissue repair. Plateletderived growth factor (PDGF) is a very well characterized example of such a polypeptide growth factor. The mitogenic property of PDGF has been augmented by the addition of insulin-like growth factor-1 (IGF-1), Antoniades et al., U.S. Pat. No. 4,861,757 and transforming growth factor alpha (TGF-.alpha.), Antoniades et al., U.S. Pat. No. 4,874,746. Levenson et al. (1985) J. Biol. Chem 260:8056-63 showed that the synthetic glucocorticoid, dexamethasone, acts synergistically with cartilage-derived growth factor (CDGF) to enhance the stimulation of DNA synthesis in quiescent Swiss 3T3 cells, approximately doubling DNA synthesis while having a neutral effect when added with PDGF. In addition, they presented data showing that the simultaneous addition of dexamethasone to PDGF stimulated cultures had no effect on DNA synthesis over that observed with PDGF alone. Web site: http://www.delphion.com/details?pn=US05149691__
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Media for normal human muscle satellite cells Inventor(s): Ham; Richard G. (Boulder, CO), St. Clair; Judith A. (Boulder, CO) Assignee(s): The University of Colorado Foundation, Inc. (boulder, Co) Patent Number: 5,143,842 Date filed: November 1, 1988 Abstract: An improved basal nutrient medium MCDB 120 for the clonal growth of human muscle satellite cells (HMSC) is described. In addition, a serum-free supplement for the clonal growth of HMSC containing serum albumin, dexamethasone, fetuin epidermal growth factor and insulin. Combination of MCDB 120 and the serum-free supplement results in a serum-free medium for growth of HMSC. The serum-free supplement can also be used with other basal nutrient media such as MCDB 131M for growth of HMSC. Addition of 5% dialyzed fetal bovine serum to the serum-free media described results in semi-defined media which allows significantly improved growth of HMSC. Excerpt(s): In the conduct of certain cell biology research, the growth and maintenance of cells derived from animal and human tissues is essential. For example, tissue culture is used extensively in studies of inherited disorders in both animals and humans. Tissue
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culture of human muscle cells is of particular interest for the study of human muscle cell disorders. While in vitro growth of human skeletal muscle cells has been achieved, relatively little attention has been given to the development of culture media optimized specifically for these cells. The development of serum-free media for cell growth allows the identification of cell growth factors and allows detailed biochemical and metabolic studies of the cell. For example, the use of serum-free media for the growth of human muscle cells facilitates the investigation of the role of growth factors in muscle differentiation. Such studies are important in the determination of the biochemical basis of certain muscle disorders. Clonal growth of mononucleate cells from embryonic chicken skeletal muscle and their fusion and differentiation to form multinucleate contractile myotubes was achieved relatively early in the history of modern cell culture (see, for example, Konigsberg, I.R. (1963) Science 140:1273-1284). Growth of human skeletal muscle cells in vitro was also achieved quite early (Hauschka, S.Dak. (1974) Dev. Biol. 37:329-344). However, despite many years of studies on growth and differentiation of skeletal muscle cells in vitro, relatively little attention has been given to the development of culture media optimized specifically for growth of muscle cells from humans or other species. Web site: http://www.delphion.com/details?pn=US05143842__ •
Medicaments Inventor(s): Challoner; Teresa E. (Regents Park, GB2), Tyers; Michael B. (Welwyn, GB2) Assignee(s): Glaxo Group Limited (london, Gb2) Patent Number: 5,482,716 Date filed: May 27, 1994 Abstract: The invention relates to the co-administration in human or veterinary medicine of 1,2,3,9-tetrahydro-9-methyl-3-[(2-methyl-1H-imidazol-1-yl)methyl]-4Hcarba zol-4-one or a physiologically acceptable salt or solvate thereof and dexamethasone or a physiologically acceptable salt or ester thereof. The two active ingredients, which may be administered separately either simultaneously or sequentially, or may be combined in a single pharmaceutical preparation, are useful in the relief and/or prevention of nausea and vomiting. Excerpt(s): This invention relates to improvements in the treatment of gastrointestinal disorders. More particularly it relates to the use of a compound having antagonist activity at 5HT.sub.3 receptors and dexamethasone in the treatment of emesis, and to pharmaceutical compositions containing the two compounds. In the aforementioned specification the compounds are described as potent and selective antagonists of 5hydroxytryptamine (5HT) at `neuronal` 5HT receptors of the type located on terminals of primary afferent nerves, and which are also present in the central nervous system. Receptors of this type are now designated 5HT.sub.3 receptors. The compounds are described as being of use in the treatment of a human or animal subject suffering from a condition caused by a disturbance of neuronal 5HT function, for example in the treatment of migraine pain or a psychotic disorder such as schizophrenia. The compounds may also be useful in the treatment of conditions such as anxiety, obesity and mania. We have found, as described in our published European Patent Specification No. 226266, that the compounds disclosed in UK Patent Specification No. 2153821A additionally promote gastric emptying, and are thus useful in the treatment of conditions which may be relieved by the promotion of gastric emptying. Such
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conditions include gastric stasis and symptoms of gastrointestinal dysfunction such as dyspepais, reflux oesophagitis, peptic ulcer and flatulence. Web site: http://www.delphion.com/details?pn=US05482716__ •
Method and device for destroying fat cells by induction of programmed cell death Inventor(s): Eiseman; Ben (Englewood, CO) Assignee(s): The Uniformed Services University of the Health Sciences (bethesda, Md) Patent Number: 6,354,297 Date filed: November 2, 1998 Abstract: The destruction of undesired fat cells is achieved by use of a device and method whereby apoptosis inducing factors are delivered to undesired fat cells. Adipose inducing factors, such as UV light, IL-1, TNF and dexamethasone are brought into contact with undesired fat cells through the use of an endoscopic device which facilitates conveyance of such factors to such cells. Repeated delivery of such adipose inducing factors can be achieved by having fiberoptic fibers and/or conveyance tubes left beneath a patient's skin in contact with undesired fat. Excerpt(s): The present invention is directed toward a method and device for destroying unwanted fat cells by induction of programmed cell death (apoptosis). In particular it relates to a method and device that places substances such as Ultra Violet light (UV) and other chemical substances which induce programmed cell death (suicide cell self destruction) in direct contact with fat cells lying underneath the skin. Obesity is a serious public health hazard, second in importance only to tobacco. Approximately 1/3 of Americans are seriously overweight according to life insurance data. In approximately 12 million Americans, obesity significantly contributes toward the cause and complications of serious disease. Such conditions include heart and lung disease, many types of cancer, diabetes, high blood pressure, and peripheral arterial disease. This is in addition to how obesity becomes a cosmetic problem. Being overly fat limits both length of life and its quality. A multi-billion dollar industry has developed in an effort to control weight. The many varied and expensive techniques employed speak to the relative ineffectiveness of the many techniques that have been tried to get rid of excess fat. Web site: http://www.delphion.com/details?pn=US06354297__
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Method and solution for treating glaucoma Inventor(s): Schwartz; Bernard (Boston, MA) Assignee(s): New England Medical Center Hospitals, Inc. (boston, Ma) Patent Number: 4,904,649 Date filed: March 27, 1987 Abstract: A method for treating glaucoma consisting of exposing the eye to a corticosteroid and a beta adrenergic agent to the eye which acts to decrease ocular pressure. Useful adrenergic agents include beta agonists antagonists, including, for example, epinephrine, dipivalyl epinephrine, betaxolol, levobunolol, and timolol. Useful steroids, which are preferably applied topically, include dexamethasone, prednisolone, cortisone, and triamcinolone. The beta adrenergic agent is administered at a
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concentration between about 10% and 20% of the concentration that the agent is administered in its normal use. The corticosteroid is administered at a concentration between 5% and 10% of the concentration that the corticosteroid is administered in its normal use. Excerpt(s): This invention is in the field of treatment of eye disease and more particularly in the area of treatments for glaucoma. Glaucoma may have a variety of causes, including hereditary predisposition, congenital malformation, disease, injury or adverse drug reaction. For example, angle-closure glaucoma occurs because the outflow of the aqueous humor is mechanically prevented by contact of the iris with the trabecular drainage meshwork and peripheral cornea. Capsular glaucoma occurs in association with the widespread deposition of degenerative substance on the lens capsule, ocular blood vessels, iris and ciliary body. Corticosteroid-induced glaucoma is due to a hereditary predisposition to increased intraocular pressure after local installation of corticosteroid-containing eyedrops. Other types of glaucoma include hypersecretion glaucoma due to the excessive formation of aqueous humor malignant glaucoma due to forward displacement of the iris and lens obliterating the anterior chamber; and open-angle glaucoma, in which the aqueous humor has free access to the trabecular meshwork. Glaucoma is treated either surgically or with antiglaucomatous agents. Examples of antiglaucomatous agents include echothiophate iodide, pilocarpine, methazolamide, timolol, and epinephrine, dipivalyl epinephrine and other epinephrine salts. Echothiophate iodide is a long-acting cholinesterase inhibitor for topical use which enhances the effect of endogenously-liberated acetycholine in parasympathetically innervated structures of the eye to increase outflow of the aqueous humor to decrease intraocular pressure. Pilocarpine is a topically applied alkaloid which acts as a parasympathomimetic agent. Methazolamide is a potent inhibitor of the enzyme carbonic anahydrase which is taken orally and acts to lower intraocular pressure by inhibiting carbonic anhydrase in the various tissues of the eye. Timolol maleate is a general beta-adrenergic receptor-blocking agent which is effective in decreasing intraocular pressure. Epinephrine bitartrate, (-)-3,4,-Dihydroxy-alpha [(methylamino) methyl] benzyl alcohol (+) tartrate (1:1) salt, is an adrenergic agent which reduces intraocular pressure by reducing the rate of aqueous formation and increasing the outflow of aqueous humor from the eye. Web site: http://www.delphion.com/details?pn=US04904649__ •
Method for delivering a therapeutic substance to a body lumen Inventor(s): Tuch; Ronald J. (Plymouth, MN) Assignee(s): Medtronic, Inc. (minneapolis, Mn) Patent Number: 5,824,048 Date filed: October 9, 1996 Abstract: A method for delivering a therapeutic substance to a body lumen utilizing an intravascular stent having a coating comprising a polymer and a therapeutic substance in a solid/solid solution with the polymer. The coating comprises a first coating layer nearer the stent body having a first concentration of therapeutic substance overlaid by a second porous coating layer having a second lesser concentration of therapeutic substance. The inclusion of a porous polymer coating layer on the stent helps retain the therapeutic substance on the stent during expansion of the stent and also controls the administration of the therapeutic substance following implantation. By this method,
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drugs such as dexamethasone can be applied to a stent, retained on a stent during expansion of the stent and elute at a controlled rate. Excerpt(s): This invention relates to intravascular stents for treatment of injuries to blood vessels and particularly to stents having a framework onto which a therapeutic substance or drug is applied. Although angioplasty procedures have increased greatly in popularity for treatment of occluded arteries, the problem of restenosis following the angioplasty treatment remains a significant problem. Restenosis is the closure of a peripheral or coronary artery following trauma to the artery caused by efforts to open an occluded portion of the artery by angioplasty, such as, for example, by balloon dilation, atherectomy or laser ablation treatment of the artery. For these angioplasty procedures, restenosis occurs at a rate of about 30-60% depending upon the vessel location, lesion length and a number of other variables. One aspect of restenosis may be simply mechanical; e.g. caused by the elastic rebound of the arterial wall and/or by dissections in the vessel wall caused by the angioplasty procedure. These mechanical problems have been successfully addressed by the use of stents to tack-up dissections and prevent elastic rebound of the vessel, thereby reducing the level of restenosis for many patients. The stent is typically inserted by catheter into a vascular lumen and expanded into contact with the diseased portion of the arterial wall, thereby providing internal support for the lumen. Examples of stents which have been successfully applied over a PTCA balloon and radially expanded at the same time as the balloon expansion of an affected artery include the stents disclosed in U.S. Pat. No. 4,733,665 issued to Palmaz, U.S. Pat. No. 4,800,882 issued to Gianturco and U.S. Pat. No. 4,886,062 issued to Wiktor which are incorporated herein by reference in their entirety. Web site: http://www.delphion.com/details?pn=US05824048__ •
Method for preparing cellular fibronectin Inventor(s): Goodheart; Clyde R. (Lincolnshire, IL), Silverman; Ralph H. (Morton Grove, IL) Assignee(s): Fibrogenex, Inc. (chicago, Il) Patent Number: 5,750,378 Date filed: January 7, 1997 Abstract: A method for producing cellular fibronectin, said method comprising incubating fibronectin-producing cells in a fibronectin production medium comprising: (a) 1.0-3.5 g/L bicarbonate salt; (b) 1.0-5.0 g/L glucose; (c) 10-30.mu.g/L dexamethasone; (d) 1-10 g/L hydrolyzed protein; and (e) 5-15.mu.g/L insulin. Excerpt(s): This invention relates to a method for preparing fibronectin and more particularly, this invention relates to a method for preparing cellular fibronectin. U.S. Pat. No. 4,728,637 (Silverman) discloses a pharmaceutical protein complex which includes fibronectin for treating humans and animals with degenerative diseases. The complex disclosed in Pat. No. 4,728,637 or, alternatively, a pure fibronectin composition, is used in the treatment of cancer resections as described in parent application 07/811,269. The aforementioned fibronectin which is produced by the inventive process herein comprises macromolecules produced from human and animal cultured cells, i.e. mesenchymal cells. As discussed in U.S. Pat. No. 4,728,637, fibronectin and procollagen are part of the compositions of that patent. Whether or not proteoglycan, laminin or elastin are present in the patent composition depends on the particular mesenchymal cell culture used to prepare the complex of the patent.
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Method of managing cattle breeding herds Inventor(s): Anderson; Lloyd L. (Ames, IA) Assignee(s): Iowa State University Research Foundation, Inc. (ames, Ia) Patent Number: 4,686,103 Date filed: July 25, 1985 Abstract: Cattle breeding herds are managed for accelerated time-controlled calving, using groups of cows predicted to calve within a period of 10 days, 1000 to 10,000 units of purified porcine relaxin are administered intramuscularly or intracervically. Auxiliary agents may also be administered such as methasone or dexamethasone. Within the selected group, parturition can be limited to time periods as short as 24 to 48 hours. Further, parturition can be accelerated from 2 to 10 days. These benefits are obtained without adverse side effects such as retained placenta or dystocia. Excerpt(s): The field of this invention is the administration of hormones to pregnant cattle for modification of calving. The method is particularly concerned with the administration of relaxin around the time of parturition. Parturition can be induced in cattle by treatment with corticoids: dexamethasone, dexamethasone trimethylacetate, flumethasone and betamethasone (Davis et al., J. Anim. Sci., 49:560-566 (1979); Welch et al., New Zeal. Vet. J., (1979), 25:111; Diskin, Vet. Record. (1982) 110:268; with prostaglandins (PGF); tham salt of PGF.sub.2.alpha. or its analogs, cloprostenol and fenprostalene (Lauderdale, Annal. Biol. Anim. Biophys. (1975) 15:415; Johnson, Acta. Vet. Scand. (1981) 77:311; and with estrogens (Henricks et al., J. Anim. Sci., (1977), 44:438. Corticoids and prostaglandins cause dystocia and retained placenta, and estrogen treatment does not reduce the incidence of retained placenta. Oxytocin injections are successful only in those animals that have had sufficient cervical softening (Veznik et al., Am. J. Vet. Res., 40:425 (1979). The peptide hormone relaxin is biologically active in female mammals. It has been prepared principally by purification from the ovaries of pregnant sows. See, for example, Sherwood et al, Arch. Biochem. Biophys. (1974) 160:185-186. The purified porcine relaxin has been studied and sequenced by Dr. Christian Schwabe and associates: Science (1977) 197:914-915; Biochem. Biophys. Res. Comm. (1976) 70(2):397-405; and Biochem. Biophys. Res. Comm. (1977) (2) 75:503-510. Web site: http://www.delphion.com/details?pn=US04686103__
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Method of pretreating an animal with a corticosteroid prior to infusion of a perfluorochemical emulsion Inventor(s): Goodin; Thomas H. (Manchester, MO), Kaufman; Robert J. (University City, MO) Assignee(s): Hemagen/pfc (st. Louis, Mo) Patent Number: 5,670,495 Date filed: April 25, 1996 Abstract: This invention is directed to a method of attenuating or preventing the adverse side-effects of a perfluorochemical (PFC) emulsion on the hemostatic system and serum chemistry of an animal. The method includes intravenously administering a
Patents 159
corticosteroid to an animal prior to intravenous administration of a PFC emulsion, in an amount sufficient to improve the adverse effects of the PFC upon the hemostatic system and serum triglyceride/enzyme levels of the animal. After administration of the corticosteroid, the PFC emulsion is administered intravenously. Preferably, the corticosteroid is dexamethasone, and the PFC is perfluorodichlorooctane. Excerpt(s): This invention is directed to the use of corticosteroids, and more particularly, to the use of corticosteroids for reducing or attenuating the adverse effects of a perfluorochemical emulsion on the hemostatic system and serum chemistry parameters of an animal. Perfluorochemical (PFC) emulsions are being developed for many different uses. Because PFCs have a high intrinsic solubility for gases, including O.sub.2 and CO.sub.2, they are especially useful as O.sub.2 /CO.sub.2 transport agents, artificial bloods, and red blood cell substitutes. PFC emulsions also are being developed as contrast agents for biological imaging. However, one of the drawbacks in using PFC emulsions in animals is that these emulsions produce certain undesirable side effects. Side effects from the intravenous infusion of a PFC emulsion have been reported in both human and animal studies. Two groups of side effects have been observed in human volunteers receiving a perfluorooctylbromide (PFOB) emulsion. PFOB, also known as Perflubron, is a PFC under development as a component of a blood-pool imaging agent known as Imagent BP. Imagent BP is a phospholipid emulsion containing ninety (90%) percent w/v Perflubron and having a mass median particle size of approximately 0.2.mu. The first group of side effects occurs within the first 2 hours after injection of the PFC emulsion. These acute effects are characterized primarily by skin flushing and backache. The second group of side effects occurs later than 2 hours post-injection and lasts generally for about a day. These delayed effects, described as a "flu-like syndrome", include fever, dizziness, and occasional nausea. S. F. Flaim, et al., "Characterization and Mechanism of Side Effects of Imagent BP (Highly Concentrated Fluorocarbon Emulsion) In Swine", Vol. 26, Investigative Radiology, November Supplement 1991, S122-S124. Web site: http://www.delphion.com/details?pn=US05670495__ •
Method to identify tumor suppressor genes Inventor(s): Fisher; Paul B. (Scarsdale, NY) Assignee(s): The Trustees of Columbia University (new York, Ny) Patent Number: 6,214,544 Date filed: March 27, 1997 Abstract: This invention provides a method of identifying a tumor suppressor gene of a cell(s). Analogous methods to identify tumor suppressors in normal cells and to identify genes associated with unknown genetic defects are also described. The feasibility of the title method was demonstrated by observing the effects of caffeine acid phenethyl ester on oncogene-tranformed CREF cells. In a second series of expts., human papillomavirus 18-transformed CREF cells were transfected with human fibroblast cDNA cloned into a pMAM-neo vector which allows dexamethasone-inducible expression. After growth in the presence of G418, neomycin resistant transformed CREF cells were obsd. Application of dexamethasone resulted in appearance of cells with normal phenotype. Excerpt(s): Throughout this application, various references are referred to by number within parentheses. Disclosures of these publications in their entireties are hereby incorporated by reference into this application to more fully describe the state of the art to which this invention pertains. Full bibliographic citation for these references may be
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found at the end of this application, preceding the claims. The carcinogenic process is complex and often involves changes in the expression of two contrasting genetic elements, i.e., positive acting oncogenes and negative acting anti-oncogenes (tumor suppressor genes) (for reviews see references 1-3). Compounds displaying selective toxicity toward transformed cells overexpressing different classes of oncogenes could prove useful as potential antitumor agents and as reagents for identifying cellular targets susceptible to modification by transforming oncogenes. Cancer is often a consequence of changes in the expression of a number of genes. These include, dominant-acting oncogenes, tumor suppressor genes, genes affecting cell cycle and genes affecting genomic stability. In the case of tumor suppressor genes, the ability to identify and isolate these elements have proven difficult often involving extensive gene mapping and technically complex and many times unsuccessful molecular approaches. Prior to the art described in this invention, no simple and efficient way of identifying and cloning tumor suppressor genes has been available. The currently described approach is simple and effective in directly identifying potentially novel human tumor suppressor genes and directly cloning these genes. The approach, termed inducible suppression cDNA cloning, is useful in identifying both oncogene specific suppressor genes and global oncogene-independent tumor suppressor genes. Web site: http://www.delphion.com/details?pn=US06214544__ •
Methods of treating myotendinitis
headache
and
functional
extraocular
and
intraocular
Inventor(s): Sucher; David F. (10 Casa Vieja, Orinda, CA 94563) Assignee(s): None Reported Patent Number: 6,106,819 Date filed: December 5, 1997 Abstract: Methods of treating headache and functional extraocular and intraocular myotendinitis by applying to the eyes of a patient being treated a compound selected from the group consisting of hydrocortisone, medrysone, prednisolone, dexamethasone, fluoromethasone, rimexolone, and loteprednol ebonate, and combinations of these compounds with other constituents. Excerpt(s): My present invention provides two novel modes of administration of treatment media for treating headache and functional extraocular and intraocular myotendinitis, as distinct from infectious, e.g., viral, bacterial or fungal extraocular and intraocular myotendinitis, or from an auto-immune disease or other systemic disease. The term "headache" is used herein to denote all eye-related headaches derived either from extraocular or an intraocular myotendinitis, and/or certain other categories of headache including vascular headache, non-eye-related tension headache and trigeminal neuralgia. The term "ocular" is used herein in its broadest acceptation to denote the outer tunic of the human eye and all parts of the human eye contained therein. Web site: http://www.delphion.com/details?pn=US06106819__
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Methods of treating ophthalmic, otic and nasal infections and attendant inflammation Inventor(s): Abshire; Robert L. (Fort Worth, TX), Cagle; Gerald (Fort Worth, TX), Stroman; David W. (Irving, TX), Yanni; John M. (Burleson, TX) Assignee(s): Alcon Manufacturing, Ltd. (fort Worth, Tx) Patent Number: 6,395,746 Date filed: September 22, 2000 Abstract: Methods of treating or preventing ophthalmic, otic, and nasal infections and attendant inflammation are described. The methods utilize ophthalmic, otic, and nasal compositions containing a new class of antibiotics (e.g. trovafloxacin). The compositions also contain one or more anti-inflammatory agents (e.g. dexamethasone). The compositions are utilized to treat ophthalmic, otic, and nasal conditions by topically applying the compositions to the affected tissues. Excerpt(s): The present invention is directed to the provision of topical antibiotic pharmaceutical compositions for the treatment of ophthalmic, otic and nasal infections, particularly bacterial infections, and to methods of treating ophthalmic, otic and nasal infections by applying those compositions to the affected tissues. The compositions and methods of the invention are based on the use of a new class of antibiotics. The compositions of the present invention may also contain one or more anti-inflammatory agents. The foregoing quinolone antibiotic compositions are generally effective in treating ophthalmic infections, and have distinct advantages over prior ophthalmic antibiotic compositions, particularly those having relatively limited spectrums of antimicrobial activity, such as: neomycin, polymyxin B, gentamicin and tobramycin, which are primarily useful against gram negative pathogens; and bacitracin, gramicidin, and erythromycin, which are primarily active against gram positive pathogens. However, despite the general efficacy of the ophthalmic quinolone therapies currently available, there is a need for improved compositions and methods of treatment based on the use of antibiotics that are more effective than existing antibiotics against key ophthalmic pathogens, and less prone to the development of resistance by those pathogens. There is an even greater need for effective topical compositions and methods for treating otic and nasal infections, particularly bacterial infections. The use of oral antibiotics to treat otic infections in children has limited efficacy, and creates a serious risk of pathogen resistance to the orally administered antibiotics. Web site: http://www.delphion.com/details?pn=US06395746__
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Pharmaceutical compositions containing granisetron and dexamethasone Inventor(s): Dott; Christopher Stuart (Redhill, GB), Sanger; Gareth John (Sawbridgeworth, GB) Assignee(s): Smithkline Beecham P.l.c. (brentford, Gb) Patent Number: 5,929,059 Date filed: July 28, 1997 Abstract: A method of treatment of nausea and vomiting is disclosed which comprises administering to a human or animal subject granisetron and an antiemetic corticosteroid. Excerpt(s): This invention relates to a method of treatment and/or prophylaxis of nausea and vomiting, comprising the administration of a compound having 5-HT.sub.3
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receptor antagonist activity. The anti-emetic properties of granisetron are potentially enhanced by administering the compound in conjunction with systemic corticosteroids, such as dexamethasone. Dexamethasone is a systemic anti-inflammatory corticosteroid, which is known to have anti-emetic properties and to be useful in the treatment of emesis resulting from chemotherapy, especially cancer chemotherapy involving the use of, for example, cisplatin. Accordingly, the present invention provides a pharmaceutical product comprising granisetron and steroid such as dexamethasone as a combined preparation for simultaneous, separate or sequential use in the treatment and/or prevention of nausea and vomiting. Web site: http://www.delphion.com/details?pn=US05929059__ •
Preparation of lipophile:hydroxypropylcyclodextrin complexes by a method using cosolubilizers Inventor(s): Irie; Tetsumi (Kumamoto, JP), Pitha; Josef (Baltimore, MD), TorresLabandeira; Juan J. (Coruna, ES) Assignee(s): The United States of America AS Represented by the Secretary of the (washington, Dc) Patent Number: 5,120,720 Date filed: September 20, 1990 Abstract: The dissolution of lipophilic compounds in aqueous solutions of hydroxypropylcyclodextrins can be accelerated by the addition of co-solubilizers, such as ethanol or ammonia, which again can be removed, together with water, by evaporation or by freeze-drying leaving lipophile: hydroxypropylcyclodextrin complexes as a residue. The co-solubilizer method was used successfully with steroid drugs (5-androstene-3.beta.,17.beta.-diol, 4-androstene-3,17-dione, dehydroepiandrosterone, dexamethasone, 5-.alpha.-dihydro-testosterone, 6methylprednisolone, and testosterone), peptides (gramicidin S) and a macrocyclic antibiotic (amphotericin B). The complexes prepared in this manner were amorphous and possessed satisfactory stability. Excerpt(s): The present invention relates to inclusion complexes between lipophilic compounds and hydroxypropylcyclodextrin complexes and to methods for preparing such utilizing co-solubilizers. The solubility in water of many lipophilic compounds may be increased through the formation of inclusion complexes with cyclodextrins and their derivatives. Szejtli in Cyclodextrin Technology (pp. 186-306) gives many examples of the uses of such solubilization in pharmaceuticals. In a majority of the described pharmaceutical applications underivatized cyclodextrins, which are crystalline, or crystalline derivatives thereof are utilized to increase the water solubility of lipophilic compounds. However, improvements in solubility could also be obtained when amorphous derivatives of cyclodextrins were used instead of crystalline derivatives (e.g., hydroxypropylcyclodextrins). (J. Pitha, U.S. Pat. No. 4,727,064; B. W. Muller, U.S. Pat. No. 4,764,604). Complexes of cyclodextrins and their crystalline derivatives with lipophiles have often been prepared by co-dissolution of components in water (Szejtli, 1.c., pp. 80-90). In some instances (e.g., vitamin D.sub.3, Szejtli, 1.c., pp. 85 and 268) addition of an organic solvent (ethanol, acetone) was necessary, but such solvents could be used only sparingly since they precipitated the cyclodextrins utilized. Today, when such cyclodextrin complexes are prepared on a technical scale, a solid phase method of preparation (kneading of components) is the method of choice.
Patents 163
Web site: http://www.delphion.com/details?pn=US05120720__ •
Serum free medium for chondrocyte cells Inventor(s): Cancedda; Ranieri (Genoa, IT), Dozin; Beatrice (Rapallo, IT) Assignee(s): Consorzio Per LA Gestione Del Centro DI Biotechnologie Avanzate (genoa, It), Istituto Nazionale Per LA Ricerca Sul Cancro (genoa, It) Patent Number: 6,617,159 Date filed: June 11, 2001 Abstract: Serum free media for growth and proliferation of chondrocytes and mesenchymal stem cells in culture are provided. A serum free medium for growth of chondrocytes includes a serum free composition comprising FGF-2, linoleic acid, ascorbic acid, B-mercaptoethanol, transferrin and dexamethasone. Further the composition comprises EGF, PDGFbb, insulin and albumin. A method for growing chondrocytes in a serum free medium comprising the composition is also provided. Also provided for mesenchymal stem cell growth, is a serum free medium which includes a composition comprising FGF-2, LIF, SCF, pantotenate, biotin and selenium and method, therefore. Excerpt(s): Bone and cartilage transplantation is an absolute need in reconstruction of bone and cartilage segments in plastic surgery, traumatic surgery or after the removal of neoplastic lesions, etc. Typically, material of human (autologous, from donors or from cadavers) or animal origin has been used for this purpose. Given the increased demand from clinicians for transplant tissues, the increased need for microbial safety in tissue transplantation, the advances in cell biology, cell differentiation and tissue engineering, the concept of rebuilding tissues from autologous or allogeneic cells expanded in vitro has become a growing field in the world of biomedical sciences. Cellular sources for skeletal repair include chondrocytes and cells committed to the chondrocyte lineage, and mesenchymal stem cells, the former specific for cartilage, the latter multipotential and therefore having the potential to be used to replace bone, cartilage and other tissues. Mesenchymal stem cells (MSCs) are found in bone marrow as well as in blood, dermis and periosteum. Although these cells are normally present at very low frequencies in bone marrow, these cells can be isolated purified and culturally expanded, for example, as described in U.S. Pat. No. 5,486,359. Typically, the ill vitro expansion of chondrocytes and MSCs takes place in culture medium supplemented with bovine serum or optimally with autologous serum from the patient. However, the presence of animal or autologous serum in chondrocyte and MSC cultures has certain disadvantages and limitations in view of the potential therapeutical applications of these cultures. Web site: http://www.delphion.com/details?pn=US06617159__
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Sialylation of N-linked glycoproteins in the baculovirus expression vector system Inventor(s): Wood; H. Alan (Ithaca, NY) Assignee(s): Boyce Thompson Institute for Plant Research, Inc. (ithaca, Ny) Patent Number: 6,472,175 Date filed: November 17, 2000
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Abstract: The present disclosure utilizes a novel approach to protein preparation in the baculovirus expression vector system (BEVS). Specifically, the present invention analyzes the effects of supplementing insect cell culture media with dexamethasone or N-acetylmannosarnine on complex glycosylation of proteins prepared via BEVS, including the addition of terminal sialic acid residues to N-linked oligosaccharides. Excerpt(s): The invention pertains to the field of protein expression systems. More particularly, the invention pertains to optimizing the N-linked glycosylation of proteins in a baculovirus expression system. Glycobiology is a newly emerging area of biotechnology. Most of the extracellular proteins of higher animals are glycoproteins, including proteins of pharmaceutical interest such as erythropoietin, tissue plasminogen, interleukins and interferons. The ubiquity and diversity of glycoproteins is matched by the breadth of functions that they have in a wide range of important biological processes. For instance, glycosylation plays an important role in hormone signal transduction and in the biological activity of immunoglobulins. Glycoproteins also play a structural role in connective tissues such as collagen. Glycosylation of proteins clearly represents one of the most important co- and post-translational events. Glycoproteins are composed of a polypeptide chain covalently bound to one or more carbohydrate moieties. There are two broad categories of glycoproteins with carbohydrates coupled through either N-glycosidic or O-glycosidic linkages to their constituent protein. The N- and O-linked glycans are attached to polypeptides through asparagine-N-acetyl-D-glucosamine and serine (threonine)-N-acetyl-D-galactosamine linkages, respectively. Complex N-linked oligosaccharides do not contain terminal mannose residues. They contain only terminal N-acetylglucosamine, galactose, and/or sialic acid residues. Hybrid oligosaccharides contain terminal mannose residues as well as terminal N-acetylglucosamine, galactose, and/or sialic acid residues. Web site: http://www.delphion.com/details?pn=US06472175__ •
Steroid eluting cuff electrode for peripheral nerve stimulation Inventor(s): Gates; James (Maple Grove, MN), Johnson; Gary (Ramsey, MN), Lee; Philip (Woodbury, MN), Stokes; Kenneth (Brooklyn Park, MN) Assignee(s): Medtronic, Inc. (minneapolis, Mn) Patent Number: 5,092,332 Date filed: February 22, 1990 Abstract: An improved electrode for establishing electrical contact with a nerve of a patient. This electrical contact may be used to sense neural activity on the nerve or to artificially stimulate it to perform various medical treatments. The electrode has an outer cuff of an insulating material which is sutured around the nerve to be contacted. A drug impregnated layer of material is positioned inside of the outer cuff. This material is a polymeric matrix which permits the drug to leach out at a predetermined rate. The drug is a steroid such as dexamethasone sodium phosphate. The actual electrical contact is produced by metallic foil which is positioned on the surface of the drug impregnated layer of material which is located inside of the cuff. An insulated lead electrically couples the metallic foil to an electronic circuit located remote from the nerve. The leaching out of the drug serves to control irritation, swelling, and impedance of the nerve/electrode interface. Excerpt(s): This application is related to Ser. No. 07/446,594, filed Dec. 6, 1989, now U.S. Pat. No. 3,009,228, entitled "Steroid Eluting Intramuscular Lead" and Ser. No.
Patents 165
07/446,865, filed Dec. 6, 1989, now U.S. Pat. No. 3,031, entitled "Nerve Electrode with Biological Substrate", both of which assigned to the assignee of this application. The present invention generally relates to implantable medical devices and more particularly relates to electrodes for electrically coupling to nerve tissue. The use of electrodes to monitor electrical activity and stimulate body tissue is quite old. U.S. Pat. No. 1,662,446 issued to R. H. Wappler teaches an early electrode system. The Wappler electrode is used for acute stimulation only, and is not implantable. Web site: http://www.delphion.com/details?pn=US05092332__ •
Tripterygium wilfordii hook F extracts and components, and uses thereof Inventor(s): Cai; Jian (Dallas, TX), Kovacs; William J. (Nashville, TN), Lipsky; Peter E. (Dallas, TX), Olsen; Nancy J. (Nashville, TN), Tao; Xue-Lian (Dallas, TX) Assignee(s): Board of Regents, University of TX System (austin, Tx) Patent Number: 5,616,458 Date filed: May 31, 1995 Abstract: The present invention provides for the use of Tripterygium wilfordii Hook F extracts and purified components thereof in the treatment of inflammation or an immune disorder with concomitant lack of steroidal effect. Extracts of this plant (T2) bound to the glucocorticoid receptor and competitively inhibited glucocorticoid mediated cellular processes, such as dexamethasone binding to the glucocorticoid receptor, glucocorticoid mediated activation of target genes, dexamethasone dependent cellular growth, with concomitant inhibition of cyclooxygenase-2 induction and inflammatory processes such as the production of prostaglandin E.sub.2. The T2 extract components triptolide and tripdiolide were effective inhibitors. The particular advantage provided by the methods herein is the treatment or prevention of inflammation and the concomitant lack of steroidal agonist effects and NSAID side effects. Conditions treatable by the present methods include inflammation and immune disorders including autoimmune disease. Excerpt(s): Rheumatoid arthritis (RA) is a chronic inflammatory disease of uncertain etiology. Since the cause is unknown, treatment has been directed at suppressing the signs and symptoms of chronic inflammation. Although many agents have been documented to decrease pain and swelling temporarily, none has been shown to have a major impact on the course of the disease. While therapeutic modalities have been developed for treatment of this disease.sup.1-4, uniform and persistent suppression of this condition has not been reported. Although current approaches remain promising, alternative means of drug development seem warranted and could yield not only new and effective treatment modalities, but also provide new insights into disease pathogenesis that could serve as the basis of future therapeutic innovations. An area to search for new therapeutic interventions for different forms of arthritis, and particularly RA and other autoimmune diseases, is that of traditional Chinese medicines. One of these traditional medicines is from Tripterygium wilfordii Hook F, a shrub-like vine from the Celastraceae family.sup.5. Tripterygium wilfordii Hook F is known to contain a number of constituents, some of which appear to be toxic.sup.6. It is known that the leaves, stem, flowers, and the skin of the roots are poisonous and that ingestion can cause death.sup.7-9. In contrast, the woody portion of the roots of the plant is much less toxic. An extract of Tripterygium wilfordii Hook F prepared from the root of the plant, designated T.sub.2, has been described in the Chinese literature for the treatment of autoimmune diseases.sup.10-26. The preparation appeared to contain therapeutic
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components, and to have a reduced toxicity compared to other available preparations of the plant. The T.sub.2 extract has been evaluated in a double-blind placebo controlled cross-over study involving 70 RA patients, these patients having had a mean duration of RA of 6 years.sup.10-11. Significant improvement in a variety of clinical parameters, particularly ESR, CRP, and Rheumatoid factor titers, was noted after 12 weeks of therapy in the experimental group compared with either baseline measurements or the placebo treated group. Of the patients treated, 82-93% noted improvement in different clinical criteria or laboratory correlates of inflammation. An immunosuppressive activity of T.sub.2 may be inferred from the finding that treatment induced inhibition of the production of IgM and IgM rheumatoid factor by the patients' peripheral blood mononuclear cells in vitro.sup.7. Toxicity, which consisted primarily of skin rash, gastrointestinal complaints and amenorrhea, was reportedly of a generally mild nature, and reversible with cessation of therapy. Web site: http://www.delphion.com/details?pn=US05616458__ •
Ultrasonic transdermal application of steroid compositions Inventor(s): Ben-Amoz; Daniel (226 Murray Dr., Allentown, PA 18104) Assignee(s): None Reported Patent Number: 4,866,050 Date filed: April 27, 1988 Abstract: A dexamethasone delivery composition includes dexamethasone disposed in a cellulosic gel, preferably a hydroxycellulose gel. Lidocaine solubilizes the dexamethasone into the gel to provide a dexamethasone composition of increased concentration and enhanced tissue penetration capability. A method for the transdermal delivery of dexamethasone includes the step of applying the dexamethasone gel composition of the invention to the tissue of a patient and applying ultrasound at the site to effect penetration of the dexamethasone. Excerpt(s): This invention relates generally to drug delivery systems and methods, and more particularly to tissue penetrating drug delivery compositions. Traditional systems for the delivery of drugs and other agents into the body each pose particular problems to the proper administration of the drug or agent. Oral administration subjects the drug or agent to the acidic environment of the stomach, where the drug or agent sometimes is chemically degraded. Enzymes in the gastrointestinal tract, surrounding tissue, or in the liver can destroy much of the drug before it enters the systemic circulation. Some drugs, although able to withstand the destructive environment of the gastrointestinal tract, are nonetheless poorly absorbed through the gastrointestinal tract. High doses of a drug must often be utilized when given orally in order to achieve a desired local concentration. Hypodermic injection and intraveneous infusion can cause infection and bruising. Controlled release of the drug over a period of time is generally not possible with this form of administration. Web site: http://www.delphion.com/details?pn=US04866050__
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Patent Applications on Dexamethasone 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 dexamethasone: •
Antiprogestins with partial agonist activity Inventor(s): Simons, Jr., S. Stoney; (Bethesda, MD) Correspondence: Needle & Rosenberg, P.C.; Suite 1000; 999 Peachtree Street; Atlanta; GA; 30309-3915; US Patent Application Number: 20030207854 Date filed: September 23, 2002 Abstract: The present invention features methods of inhibiting progestin activity in a cell or in a subject in need of such inhibition, and methods of treating or preventing progestin-dependent conditions in a subject in need of such treatment or prevention. The methods include administering an effective amount of a C-17-derivatized dexamethasone antiprogestin to the cell or the subject. The invention also provides methods of screening substances for progestin or antiprogestin activity, and methods of detecting progestins, progestin agonists, or antiprogestins in a sample, using the C-17derivatized dexamethasone antiprogestins of the invention. Excerpt(s): This invention relates generally to the identification of a class of compounds that behave as antiprogestins with partial agonist activity, and methods for their use. A primary effect of steroid hormones is to regulate the rates of transcription of responsive genes during development, differentiation, and homeostasis. The basic steps appear to be the same for all members of the steroid/nuclear receptor superfamily that bind ligands. After a ligand enters a cell and binds to its cognate intracellular receptor protein, the resulting receptor-ligand complex undergoes activation to acquire an increased affinity for DNA. This receptor-ligand complex then attaches to specific, biologically active DNA sequences, called hormone response elements (HREs) and, in association with various cofactors, is thought to interact with the transcriptional machinery to modify the rates of transcription of the target gene. The human progesterone receptor (PR) occurs as three different isoforms: PR-A, PR-B, and PR-C (Kastner et al., EMBO J 9:1603-1614, 1990; Wei et al., Mol Endo 10:1379-1387, 1996), of which PR-A and PR-B are the most abundant. However, the ratio of PR-A vs. PR-B isoforms is not constant among target tissues, and this can alter the cellular response, because the activity of each isoform can vary. Web site: http://appft1.uspto.gov/netahtml/PTO/search-bool.html
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Delivery of microparticle-conjugated drugs for inhibition of stenosis Inventor(s): Iversen, Patrick L.; (Corvallis, OR), Kipshidze, Nicholas; (New York, NY) Correspondence: Perkins Coie Llp; P.O. Box 2168; Menlo Park; CA; 94026; US Patent Application Number: 20030206960 Date filed: July 2, 2002
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This has been a common practice outside the United States prior to December 2000.
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Abstract: Administration of a formulation comprising a antirestenotic compound conjugated to a microparticle carrier is effective to inhibit stenosis formation in a blood vessel. Such stenosis typically results, in the absence of treatment, from trauma to a vessel, such as an incision, excessive pressure, an angioplasty procedure and/or stent implantation. The antirestenotic compound is typically an antiproliferative, immunosuppressive, or antiinflammatory drug, such as rapamycin, tacrolimus, paclitaxel, dexamethasone, or an active analog or derivative, an antisense oligonucleotide, or combinations thereof. The microparticle carrier comprises a suspension of gas-filled microbubbles or biocompatible polymeric microparticles, in a pharmaceutically acceptable liquid vehicle, and is effective to deliver the conjugated therapeutic to the site of vessel injury. Excerpt(s): This application is a continuation-in-part of U.S. Ser. No. 10/138,589 filed on May 3, 2002, which is incorporated herein in its entirety by reference. The present invention relates to methods of treating or preventing hyperproliferative disease, e.g. stenosis, in blood vessels, and in particular to preventing stenosis following vascular injury, by delivery of a microparticle-conjugated antirestenotic drug, such as rapamycin, to a site of vascular injury. Albiero R et al., "Short- and intermediate-term results of.sup.32P radioactive b-emitting stent implantation in patients with coronary artery disease." Circulation 101:18-26 (2000). Web site: http://appft1.uspto.gov/netahtml/PTO/search-bool.html •
Detection of hypertension using immunoreactive metabolic products Inventor(s): Capdevila, Jorge H.; (Nashville, TN), Kim, Hyesook; (Bloomfield Hills, MI), Kroetz, Deanna; (San Francisco, CA), Novak, Raymond R.; (West Bloomfield, MI) Correspondence: Kohn & Associates; 30500 Northwestern Highway, Suite 410; Farmington Hills; MI; 48334; US Patent Application Number: 20020025544 Date filed: September 4, 2001 Abstract: A method to assess hypertension by measuring the amount of free and conjugated hydroxyeicosatrienoic acids (DHETs) and metabolites of DHETs, which are metabolites of arachidonic acid (AA) epoxygenases and epoxide hydrolases, in a biological sample which contains the DHETs (using any methods including GC/MS or ELISA) is disclosed. The method further included determining the amount of molecules containing a DHET-specific epitope immunoreactive with antibodies produced against DHETs present in the sample. This amount is compared with a control sample(s). Hypertension is determined through the comparison wherein the amount of increase of free and conjugated DHETs and metabolites of DHETs in the sample isolated from an organism. The present invention also provides a method to assess catalytic activity of AA epoxygenases using immunoassays by subtracting the amounts of NADPHindependent epoxyeicosatriencic acids (EETs) from total (NADPHdependent+independent) EETs. The present invention also provides a method to decrease hepatic M epoxygenase expression including 2C23 by treatment of rats with a glucocorticoid including dexamethasone. Excerpt(s): This application is a conversion of U. S. Provisional Patent Application Ser. No. 60/136,475, filed May 28, 1999, claiming benefit under 35 U.S.C.sctn.119 (e), and which is incorporated herein by reference. This invention relates to a method to analyze arachidonic acid (AA)-derived products which are immunoreactive with antibodies
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produced against hydroxyeicosatrienoic acids (DHETs). More specifically, the present invention relates to a method which can be used to facilitate investigations of the physiological and pathophysiological roles of the metabolic products of arachidonic acid epoxygenases and epoxide hydrolases. The present invention also relates to a method to assess catalytic activity of AA epoxygenases using immunoassays and a method to decrease hepatic AA epoxygenase expression by treatment with glucocorticoids. AA is a component of cellular membranes and plays a critical role as a mediator of cell and organ function through its metabolic cascade. The AA cascade includes prostaglandinsynthases, lipoxygenases, and cytochromes P450 (CYPs). The CYP pathway is composed of lipoxygenases-like (allylic oxidation),.omega./.omega.-1 oxygenases and epoxygenases (olefin epoxidation), which metabolize AA to produce 5-, 8-, 9-, 11-, 12-, and 15-hydroxyeicosatetraenoic acids (HETEs), 16- to 20-hydroxyeicosatetraenoic acids (OH--AAs), and 5,6-, 8,9-, 11,12- and 14,15-epoxyeicosatrienoic acids (EETs), respectively (1). Epoxide hydrolases hydrolyze biologically active EETs to their corresponding dihydroxyeicosatrienoic acids (DHETs). Web site: http://appft1.uspto.gov/netahtml/PTO/search-bool.html •
Drug eluting coatings for medical implants Inventor(s): Hsu, Li-Chien; (Mission Viejo, CA) Correspondence: Li-chien Hsu; 22181 Abrazo; Mission Viejo; CA; 92691; US Patent Application Number: 20040037886 Date filed: April 26, 2003 Abstract: Drug eluting coating compositions are composed of at least one therapeutic agent dispersed in modified, biologically active binders. The therapeutic agents included in the coating composition are paclitaxel, sirolimus, tacrolimus, everolimus, actinomycin-D, dexamethasone, mycophenolic acid, cyclosporins, estradiol, and derivatives and analogs thereof. These therapeutic agents are applied to the surface of the medical device by a modified, biologically active binders. By using these biologically active binders, the therapeutic agents can be applied to at least one surface of a medical implant without using inert polymer carriers. Excerpt(s): This application claims the benefit of U.S. Provisional Application No. 60/405,933, filed Aug. 26, 2002, and whose entire contents are hereby incorporated by reference. The implantation or insertion of a medical device into a patient's body can cause the body to exhibit adverse physiological reactions. The reactions may range from infections to the formation of emboli or clots in blood vessels. One particularly adverse physiological reaction is the result of epithelial damage to the cardiovasculature. That is, the vasculature can be damaged during procedures such as percutaneous transluminal coronary angioplasty (PCTA). As a result of damage to the epithelium of the vasculature, a cascade of physiological events may result in the re-narrowing (restenosis) of the vessel. While not completely understood, restenosis may be the result of smooth muscle cell proliferation in the intimal layers of the vessel. Restenosis of an artherosclerotic coronary artery after PTCA occurs in 10-50% of patients undergoing this procedure and subsequently requires either further angioplasty or coronary artery bypass graft. In order to maintain the patency of the vessel, intravascular stents have been developed as a mechanical means of preventing the collapse or abrupt closure of the dilated segment of the artery. Web site: http://appft1.uspto.gov/netahtml/PTO/search-bool.html
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Method for induced lactation Inventor(s): Klusmeyer, Tim H.; (O'Fallin, MO), McGrath, Michael F.; (Wildwood, MO), Patel, Kanaiyalal R.; (St. Louis, MO), Reed, Edward Alan; (St. Peters, MO), Schenkel, Robert H.; (St. Louis, MO), Vicini, John L.; (Chesterfield, MO) Correspondence: Howrey Simon Arnold & White; 750 Bering Drive; Houston; TX; 77057-2198; US Patent Application Number: 20020058621 Date filed: July 20, 2001 Abstract: Methods for effecting mammary secretion of milk from an animal, without the benefit of an immediately preceding pregnancy are provided. An exemplary embodiment the method comprises elevating an animal's estradiol and progesterone blood level sufficient to maintain a milk-secretion stimulating amount for approximately 5 to 12 consecutive days, wherein the day of the first elevation is defined to be day 0; and elevating an animal's somatotropin blood level sufficient to maintain a milksecretion stimulating amount for at least 20 days from day 0. In any embodiment the method also optionally includes administering to the animal a milk-secretion stimulating amount of dexamethasone on approximately day 13 of the treatment. Furthermore, any embodiment the method may also optionally include adjusting the photo-period to which the animal is exposed in order to stimulate milk secretion. Any embodiment the method may also include physical stimulation of the animal's mammary gland. Excerpt(s): This application claims priority to Provisional Application Serial No. 60/220,012 filed Jul. 21, 2001. The present invention relates to the field of enhancing milk production in mammals. More particularly, it concerns pharmaceutical compositions and methods of using said compositions in a manner effective to induce milk production in previously non-lactating animals. Commercial raising of cattle for dairy production requires proper management. In addition to the various husbandry concerns such as herd health and nutrition, a critical management area for economic survival of any cattle operation, is the breeding management of the cows. In the case of dairy cows, the cows will not produce milk unless they have a calf, which is again dependent upon successful breeding management. Web site: http://appft1.uspto.gov/netahtml/PTO/search-bool.html
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Method for treating rheumatoid arthritis with composition containing histone Inventor(s): Bae, Insoo; (Daejon, KR), Hong, Seung-Suh; (Daejon, KR), Jung, NeonCheol; (Daejon, KR), Kim, Dong-soo; (Seoul, KR), Lee, Hyun-Soo; (Seoul, KR), Yi, YongWeon; (Daejon, KR), Yim, Heajoon; (Daejon, KR) Correspondence: Darby & Darby P.C.; Post Office Box 5257; New York; NY; 10150-5257; US Patent Application Number: 20030007964 Date filed: June 12, 2002 Abstract: The present invention relates to a novel use of histone and an active fragment thereof and provides a pharmaceutical composition containing histone as an active ingredient to improve the symptoms of progressive, inflammatory and autoimmune arthritis. The pharmaceutical composition of the present invention includes histone,
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especially histone H1, histone H2A, histone H2B, histone H3, histone H4, an active fragment thereof, and a mixture thereof as an active ingredient, and could include pharmacologically approved carriers if necessary. Histone or its active fragment lowered induction of arthritis and reduced arthritis index more effectively than steroidal dexamethasone and also had a significant preventive effect. Excerpt(s): The present invention relates to the use of histone or an active fragment thereof in improving inflammatory symptoms of arthritis by many possible mechanisms. Histone or an active fragment thereof lowers induction of arthritis and reduces the arthritis index more effectively than steroidal dexamethasone and also has a significant preventive effect. The present invention relates to biologically active compositions to improve symptoms of progressive, inflammatory and autoimmune arthritis. Despite the development of many arthritis drugs, arthritis remains a world wide serious disease due to an increasing aging population. Even though the death rate due to arthritis is low, the quality of life of an individual who suffers from this disease is sacrificed with lowered activity level and productivity. Among many types of arthritis, the most significant one is rheumatoid arthritis. Rheumatoid arthritis is an autoimmune disease caused by the action of auto-reactive T lymphocytes. T lymphocytes cause rheumatoid arthritis via secondary hypersensitivity. It is not fully understood which antigen is recognized by T lymphocytes to cause this disease. Type II collagen is known to be the most probable one, but other possibilities cannot be excluded. Anti-histone autoantibody has been discovered even though it is not clear that this antibody is the cause of the disease. Web site: http://appft1.uspto.gov/netahtml/PTO/search-bool.html •
Method of treating middle ear infections Inventor(s): Conroy, Peter J.; (Fort Worth, TX), Wall, G. Michael; (Fort Worth, TX) Correspondence: Alcon Research, LTD.; Patrick M. Ryan(q-148); R&d Counsel; 6201 South Freeway; Fort Worth; TX; 76134-2099; US Patent Application Number: 20030139382 Date filed: September 13, 2002 Abstract: Aqueous suspension formulations containing dexamethasone and ciprofloxacin are disclosed for the treatment of middle ear infections in human patients having an open tympanic membrane. Excerpt(s): This application claims priority to U.S. Provisional Application, Serial No. 60/323,951, filed Sep. 21, 2001. This invention relates to the use of formulations of ciprofloxacin and dexamethasone to treat otic infections. Specifically, the invention relates to the topical use of such a fixed combination to treat middle ear infections in humans. External ear infections, known as acute otitis externa ("AOE"), are currently treated with oral antibiotics, topical single-entity antibiotics, or topical antibiotic/steroid combination products. An example of an oral antibiotic product used to treat AOE is AUGMENTIN.RTM. (amoxicillin and clavulanic acid). An example of a single-entity antibiotic product approved for topical use in treating AOE is FLOXIN.RTM. (ofloxacin). Examples of combination products approved for this use include CORTISPORIN.RTM. (hydrocortisone, neomyciri sulfate, and polymyxin b sulfate) and CIPRO.RTM.HC (ciprofloxacin and hydrocortisone). A product called SOFRADEX (gramicidin, framycetin and hydrocortisone) is available in some European countries
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and in Australia. External ear infections typically involve bacteria of the following types: Pseudomonas aeruginosa, Staphylococcus aureus. Staphylococcus sp. and Coryneforms. Web site: http://appft1.uspto.gov/netahtml/PTO/search-bool.html •
Methods of enhancing lysosomal storage disease therapy by modulation of cell surface receptor density Inventor(s): Cheng, Seng H.; (Wellesley, MA), Zhu, Yunxiang; (Wayland, MA) Correspondence: Hamilton, Brook, Smith & Reynolds, P.C.; 530 Virginia Road; P.O. Box 9133; Concord; MA; 01742-9133; US Patent Application Number: 20040029779 Date filed: April 4, 2003 Abstract: Methods of modulating uptake of extracellular lysosomal enzymes by administering a pharmaceutical agent and methods of treating a lysosomal storage disease (such as Gaucher disease, Pompe disease, Fabry disease or Niemann-Pick disease) or enhancing enzyme replacement therapy or gene therapy, comprising administering a pharmaceutical agent such as dexamethasone, glucose or insulin, are provided. Excerpt(s): This application claims the benefit of U.S. Provisional Application No. 60/370,747 filed Apr. 5, 2002. The entire teachings of the above application are incorporated herein by reference. Lysosomal storage diseases are a group of rare genetic disorders comprising more than forty individual diseases. Currently, a promising treatment for these diseases is enzyme replacement therapy (ERT). Gene therapy, which employs a depot expression strategy where high-level expression of lysosomal enzymes in one organ can be secreted into the blood stream and carried to other organs for uptake, is another promising option. One of the major issues with ERT treatment for lysosomal storage diseases is that the infused lysosomal enzymes are rapidly removed from the blood stream by the liver, either through carbohydrate-binding receptors or non-specifically. For substrate deprivation and small molecule therapies, ERT, gene therapy, and combinations thereof, more efficient uptake of lysosomal enzymes circulating in the blood stream by target cells and/or organs would be desirable. It has now been found that the uptake of extracellular lysosomal enzymes by cells can be increased by up-regulating the cell surface expression and density of carbohydrate binding receptors. For example, up-regulation of the mannose receptor on macrophage cells by a glucocorticosteroid such as dexamethasone, for example, increases the target organ uptake of glucocerebrosidase for the treatment of Gaucher disease (see, e.g., Examples 1 and 2). Furthermore, the dexamethasone-induced increase in glucocerebrosidase uptake is selective for macrophage cells, which are the cells most severely affected by Gaucher disease. Likewise, up-regulation of the mannose 6phosphate/IGF-II receptor (M6P/IGF-II) by insulin/glucose on muscle cell surfaces increases target organ uptake of acid alpha-glucosidase which is needed for the treatment of Pompe's disease (see, e.g., Examples 3 and 4). Based on these discoveries, methods of treating lysosomal storage diseases are contemplated herein. Web site: http://appft1.uspto.gov/netahtml/PTO/search-bool.html
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Novel anti-inflammatory peptides Inventor(s): Kim, Soo-Youl; (Seoul, KR), Sohn, Joon-Hong; (Seoul, KR) Correspondence: Barlow, Josephs & Holmes, LTD.; 101 Dyer Street; 5th Floor; Providence; RI; 02903; US Patent Application Number: 20020192780 Date filed: April 4, 2002 Abstract: The present invention provides novel anti-inflammatory peptides having the amino acid of the SEQ ID NO:1(KVLDPVKG); SEQ ID NO:2(KVLDGQDP) or SEQ ID No:3(DPVKG) containing inhibitory effects of transglutaminase and phospholipase A.sub.2, their derivatives, pharmaceutical compositions containing the aforesaid peptides, and methods for preventing inflammation by using the same. The peptides, derivatives thereof, analogs thereof and the pharmaceutical compositions containing the same of the present invention show the higher anti-inflammatory activities than the existing known peptides or steroidal anti-inflammatory drugs, such as dexamethasone. Excerpt(s): The present invention provides novel anti-inflammatory peptides containing inhibitory effects of transglutaminase and phospholipase A.sub.2, their derivatives, pharmaceutical compositions containing the aforesaid peptides, and methods for preventing inflammation by using the same. An inflammatory reaction is a complex biochemical and cytological phenomena that are manifested physiologically in tissue by edema, pain and leukocyte infiltration. The most effective drugs for the inflammation are glucocorticoids. Glucocorticoids, conventional anti-inflammatory steroidal drugs, have been proved to exhibit an excellent activity against rheumatoid arthritis and others by inhibiting or preventing various inflammatory reactions which is caused by radioactive, mechanical, chemical, infectious and immunological stimulation. However, as the steroidal anti-inflammatory drugs are used widely, recently various harmful side effects caused by their abuse have resulted in serious problems. The steroidal antiinflammatory drugs clinically causes two categories of side effects: the symptoms caused by a sudden break after a long-term administration and those others caused by too much use for a long time. After long-term administration of adrenocortical hormones, abruptly stopping it causes symptoms such as general prostration, fever, myalgia, arthralgia, and decrease of appetite, etc. as an outcome of the renal paresis. It also causes the increased opportunity for bacterial and viral infections, body weight increase, body form change and insomnia. So, there have been several problems for their applications, and thus it is desirable to develop a new anti-inflammatory drug without causing any side effects. To avoid these side effects, we need to develop specific inhibitors at certain inflammatory pathway. PLA.sub.2 is the initial step enzyme to generate arachidonic acid from phospholipids that causes that inflammation at several steps later as prostaglandins and leukotrienes. Therefore, blocking of PLA.sub.2 activation may be the best way to prevent inflammation. Indeed steroid is a powerful therapeutic approach although precise mechanism is not yet clear. One of the key mechanisms of steroid has been proposed that anti-inflammatory effect is mediated by induction of anti-inflammatory proteins. Glucocorticoid induces many proteins such as lipocortins, inhibitory proteins of phospholipase A.sub.2 (PLA.sub.2)(Flower, R. J. et al., Nature 278, 456-459, 1979). Numerous studies have revealed that their antiinflammatory effects are mediated by the induction of lipocortins (Flower, R. J., et al., Adv. Inflamm. Res. 7, 61-69, 1984) and uteroglobins (Miele et al., Endocr. Rev. 8, 474.about.490, 1987). Lipocortins (annexins) are a class of proteins that share structural and functional features. In the functional feature, Miele et al. identified a region of sequence similarity between uteroglobin and lipocortin-1. Further they designed several
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synthetic peptides corresponding to the region of highest similarity between uteroglobin and lipocortin-1: nonapeptides, so called antiflammins (AFs), corresponding to uteroglobin residues 39-47 and lipocortin-1 residues 246-254. Both peptides were shown to be phospholipase A.sub.2 (PLA.sub.2) inhibitors in vitro and were effective in a classic model of acute inflammation in carrageenan-induced rat footpad edema (Miele et al., Nature 335, 726-730, 1988). However, it is controversial whether or not AFs have any inhibitory effect on PLA.sub.2 as well as anti-inflammatory activity in vivo (Hope, W. C., et al. Agents Actions 34, 77-80, 1991; Marki, F., et al. FEBS Lett. 264, 171-175, 1990; Van Binsbergen, J., et al FEBS Lett. 247, 293-297, 1989). The existing antiflammin or PLA.sub.2 inhibitor alone was not able to show potent anti-inflammatory effects like dexamethasone. Web site: http://appft1.uspto.gov/netahtml/PTO/search-bool.html •
Pai-1 determination and use thereof Inventor(s): Andreasen, Peter; (Dragor, DK), Brunner, Nils; (Virum, DK), Dano, Keld; (Charlottenlund, DK), Nielsen, Lars S.; (Kokkedal, DK) Correspondence: Browdy And Neimark, P.L.L.C.; 624 Ninth Street, N.W.; Washington; DC; 20001; US Patent Application Number: 20020012950 Date filed: August 7, 2001 Abstract: A monoclonal antibody which binds a human endothelial type plasminogen activator inhibitor (PAI-1) produced by dexamethasone-treated human HT-1080 fibrosarcoma cells may be used, inter alia, for determining PAI-1 protein abundance in tumor tissue or a sample of a body fluid. Measurements of this parameter may be useful in predicting the presence or metastasis of a tumor, or of predicting the progression of a known malignant tumor. Excerpt(s): The present invention is a continuation-in-part application of application Ser. No. 900,364 filed Jun. 18, 1992, which is a Rule 1.62 continuation application of Ser. No. 752,990 filed Sep. 3, 1991, which is a Rule 1.62 continuation application of Ser. No. 035,995 filed Mar, 11, 1987. This invention relates to monoclonal antibodies, a method of producing such antibodies, hybridoma cells capable of producing the antibodies and uses of the antibodies. Furthermore, the invention relates to the prognostic and diagnostic use of PAI-1 determinations in e.g. plasma samples, and to measurement of uPA:PAI-1 complexes and uses thereof. The fusion of mouse myeloma cells with spleen cells from immunized mice (Kohler and Milstein, Nature (1975), 256, 496-497) was the first indication that it is possible to obtain continuous cell lines which produce homogenous (so-called "monoclonal") antibodies. Since then, a large number of attempts have been made to produce various hybrid cells (so-called "hybridomas") and to employ the antibodies formed by these cells for various scientific investigations (cf. Current Topics in Microbiology and Immunology, volume 81--"Lymphocyte Hybridomas", F. Melchers et al., Springer-Verlag (1978) and references therein; C. J. Barnstable et al., Cell, (1978), 14, 9-20; P. Parham., W. F. Bodmer, Nature (1978), 276, 397-399; Handbook of Experimental Immunology, 3rd edition, vol. 2, D. M. Wier, editor, Blackwell, 1978, Chapter 25, Chem. Eng. News, 15-17 (1979); Kennett, R. H., McKearn, J. T., and Bechtol, K. B. (1980) Monoclonal Antibodies. Hybridomas: A New Dimension in Biological Analysis (Plenum, New York)). These reports describe the principal techniques for the production of monoclonal antibodies by hybridomas.
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Processes for clonal growth of hepatic progenitor cells Inventor(s): Kubota, Hiroshi; (Chapel Hill, NC), Reid, Lola M.; (Chapel Hill, NC) Correspondence: Patent Adminstrator; Katten Muchin Zavis Rosenman; 525 West Monroe Street; Suite 1600; Chicago; IL; 60661-3693; US Patent Application Number: 20030032182 Date filed: May 1, 2002 Abstract: A method of propagating mammalian endodermally derived progenitors such as hepatic progenitors, their progeny, or mixtures thereof is developed which includes culturing mammalian progenitors, their progeny, or mixtures thereof on a layer of embryonic mammalian feeder cells in a culture medium. The culture medium can be supplemented with one or more hormones and other growth agents. These hormones and other growth agents can include insulin, dexamethasone, transferrin, nicotinamide, serum albumin,.beta.-mercaptoethanol, free fatty acid, glutamine, CUSO.sub.4, and H.sub.2SeO.sub.3. The culture medium can also include antibiotics. Importantly, the culture medium does not include serum.The invention includes means of inducing the differentiation of the progenitors to their adult fates such as the differentiation of hepatic progenitor cells to hepatocytes or biliary cells by adding, or excluding epidermal growth factor, respectively.The method of producing mammalian progenitors is useful in that the progenitors can be used subsequently in one or more of the following processes: identification of growth and differentiation factors, toxicological studies, drug development, antimicrobial studies, or the preparation of an extracorporeal organ such as a bioartificial liver. Excerpt(s): The present invention relates to novel conditions for clonal growth of mammalian hepatic progenitors, including pluripotent cells, stem cells, and other early hepatic progenitor cells. In particular, the invention relates to methods of propagating hepatic progenitor cells using defined culture medium and feeder cells in co-cultures. Moreover, the invention relates to the cells used as feeders and capable of sustaining hepatic progenitor cell growth. Identification of multipotential progenitor cell populations in mammalian tissues is important both for clinical and commercial interests and also for understandings of developmental processes and tissue homeostasis. Progenitor cell populations are ideal targets for gene therapy, cell transplantation and for tissue engineering of bioartificial organs (Millar, A D. 1992 Nature 357, 455; Langer, R. and Vacanti, J. P. 1993 Science 260, 920; Gage, F. H. 1998 Nature 392, 18). The existence of tissue-specific, "determined" stem cells or progenitors having high growth potential and/or pluripotentiality is readily apparent from studies on hematopoictic stem cells (Spangrude, G. J. et al. 1988 Science 241, 58), neuronal stem cells (Davis, A. A., and Temple, S. 1994 Nature 372, 263; Stemple, D. L., and Anderson, D. J. 1992 Cell 71, 973) and epidermal stem cells (Jones, P. H. and Watt, F. M. 1993 Cell 73, 713), each having been identified clonally by using the particular methods appropriate for that tissue. These progenitors are regarded as the cells responsible for normal hematopoietic, neuronal or epidermal tissue homeostasis and for regenerative responses after severe injury (Hall, P. A., and Watt, F. M. 1989 Development 106, 619). Web site: http://appft1.uspto.gov/netahtml/PTO/search-bool.html
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Topical suspension formulations containing ciprofloxacin and dexamethasone Inventor(s): Bhagat, Haresh G.; (Fort Worth, TX), Singh, Onkar N.; (Arlington, TX) Correspondence: Alcon Research, LTD.; R&d Counsel, Q-148; 6201 South Freeway; Fort Worth; TX; 76134-2099; US Patent Application Number: 20010034339 Date filed: May 25, 2001 Abstract: Suspension formulations containing dexamethasone and ciprofloxacin are disclosed. The formulations contain a nonionic polymer, a nonionic surfactant and an ionic tonicity agent, but are physically stable and easily re-suspended. The formulations are intended for topical application to the eye, ear or nose. Excerpt(s): This application claims priority to co-pending U.S. Provisional Application, U.S. Ser. No. 60/155,942, filed Sep. 24, 1999. This invention relates to topically administrable ophthalmic and otic formulations of ciprofloxacin and dexamethasone. The formulations of the present invention are suspensions that have excellent physical stability and are characterized by their easy and ready resuspendibility. Specifically, the invention relates to stable suspension formulations of ciprofloxacin and dexamethasone that lack a nonionic tonicity agent, such as glycerol or mannitol. Spanish Patent Application No. 2,065,846 A1 (Feb. 16, 1995) discloses topically administrable ophthalmic and otic antibiotic/steroid combination products. Examples 1-3 illustrate ophthalmic suspension formulations containing certain drug combinations with excipients including nonionic polymers and nonionic surfactants. Example 1 is a formulation of clobetasone and lomefloxacin that contains a nonionic tonicity agent (glycerin). Example 2 is a formulation of fluoromethalone and norfloxacin that contains an ionic tonicity agent (sodium chloride). Example 3 is a formulation of ciprofloxacin and dexamethasone that contains a nonionic tonicity agent (mannitol). Web site: http://appft1.uspto.gov/netahtml/PTO/search-bool.html
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Two-component anti-emetic composition Inventor(s): Jannetta, Anthony; (Haverford, PA) Correspondence: Patent Adminstrator; Katten Muchin Zavis; Suite 1600; 525 West Monroe Street; Chicago; IL; 60661; US Patent Application Number: 20020055495 Date filed: September 5, 2001 Abstract: The invention relates to an anti-emetic composition containing dexamethasone (DEX) and metoclopramide (MTC). In a particular embodiment, a composition containing DEX:MTC in a relative weight ratio of about 1 to less than 1.25 is found to be effective in providing relief from the discomfort caused by symptoms of both vomiting and nausea in all patients receiving the composition. Alternatively, an effective suppository composition may contain DEX:MTC in a relative weight ratio of about 1:112.5. Other effective compositions and methods of their use are also disclosed. Excerpt(s): This application claims the benefit of an earlier-filed provisional application No. 60/229,547 filed Sep. 5, 2000, the entire disclosure of which is incorporated herein by reference. The present invention relates to both a therapeutic composition comprising a synergistic combination of antiemetic drugs and to a method for treating emesis, including nausea. Nausea and vomiting can follow the administration of many drugs,
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particularly anticancer or chemotherapeutic agents. The symptoms also often accompany infectious and non-infectious gastrointestinal disorders. 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 dexamethasone, 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 “dexamethasone” (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 dexamethasone. You can also use this procedure to view pending patent applications concerning dexamethasone. Simply go back to http://www.uspto.gov/patft/index.html. Select “Quick Search” under “Published Applications.” Then proceed with the steps listed above.
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CHAPTER 7. BOOKS ON DEXAMETHASONE Overview This chapter provides bibliographic book references relating to dexamethasone. In addition to online booksellers such as www.amazon.com and www.bn.com, excellent sources for book titles on dexamethasone include the Combined Health Information Database and the National Library of Medicine. Your local medical library also may have these titles available for loan.
Book Summaries: Online Booksellers Commercial Internet-based booksellers, such as Amazon.com and Barnes&Noble.com, offer summaries which have been supplied by each title’s publisher. Some summaries also include customer reviews. Your local bookseller may have access to in-house and commercial databases that index all published books (e.g. Books in Print®). IMPORTANT NOTE: Online booksellers typically produce search results for medical and non-medical books. When searching for “dexamethasone” at online booksellers’ Web sites, you may discover non-medical books that use the generic term “dexamethasone” (or a synonym) in their titles. The following is indicative of the results you might find when searching for “dexamethasone” (sorted alphabetically by title; follow the hyperlink to view more details at Amazon.com): •
Dexamethasone regulates glutamine synthetase expression in rat skeletal muscles (SuDoc NAS 1.26:182935) by NASA; ISBN: B00010OEP6; http://www.amazon.com/exec/obidos/ASIN/B00010OEP6/icongroupinterna
The National Library of Medicine Book Index The National Library of Medicine at the National Institutes of Health has a massive database of books published on healthcare and biomedicine. Go to the following Internet site, http://locatorplus.gov/, and then select “Search LOCATORplus.” Once you are in the search area, simply type “dexamethasone” (or synonyms) into the search box, and select “books
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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 •
Preliminary abstracts from conference on a decade of anti-inflammatory steroids, from cortisone to dexamethasone. New York, New York, December 15-16, 1958. Author: Schering Corporation; Year: 1958
Chapters on Dexamethasone In order to find chapters that specifically relate to dexamethasone, an excellent source of abstracts is the Combined Health Information Database. You will need to limit your search to book chapters and dexamethasone 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 “dexamethasone” (or synonyms) into the “For these words:” box. The following is a typical result when searching for book chapters on dexamethasone: •
Steroids Source: in Haybach, P.J. Meniere's Disease: What You Need to Know. Portland, OR: Vestibular Disorders Association. 1998. p. 171-176. Contact: Available from Vestibular Disorders Association. P.O. Box 4467, Portland, OR 97208-4467. (800) 837-8428. E-mail:
[email protected]. Website: www.vestibular.org. PRICE: $24.95 plus shipping and handling. ISBN: 0963261118. Summary: This chapter is from a book that provides information for people who have or suspect they have Meniere's disease and want to know more about its diagnosis and treatment, as well as strategies for coping with its effects. Written in nontechnical language, the chapter discusses the use of steroids (corticosteroids) for people with Meniere's disease. In the case of treatment for Meniere's disease, steroids are given in an effort to treat the inflammation that may be present within the inner ear or to stop an immune reaction that may be present. The author discusses systemic steroids and local steroids. For each category, the author briefly reviews the possible side effects, patient selection issues, preventing problems, and coping tips. The author briefly addresses the
11
In addition to LOCATORPlus, in collaboration with authors and publishers, the National Center for Biotechnology Information (NCBI) is currently adapting biomedical books for the Web. The books may be accessed in two ways: (1) by searching directly using any search term or phrase (in the same way as the bibliographic database PubMed), or (2) by following the links to PubMed abstracts. Each PubMed abstract has a "Books" button that displays a facsimile of the abstract in which some phrases are hypertext links. These phrases are also found in the books available at NCBI. Click on hyperlinked results in the list of books in which the phrase is found. Currently, the majority of the links are between the books and PubMed. In the future, more links will be created between the books and other types of information, such as gene and protein sequences and macromolecular structures. See http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=Books.
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controversial use of transtympanic administration of the steroid dexamethasone (Decadron). 10 references.
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CHAPTER 8. PERIODICALS DEXAMETHASONE
AND
NEWS
ON
Overview In this chapter, we suggest a number of news sources and present various periodicals that cover dexamethasone.
News Services and Press Releases One of the simplest ways of tracking press releases on dexamethasone 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 “dexamethasone” (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 dexamethasone. 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 “dexamethasone” (or synonyms). The following was recently listed in this archive for dexamethasone: •
High-dose dexamethasone effective for immune thrombocytopenic purpura Source: Reuters Medical News Date: August 28, 2003
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Dexamethasone may benefit mechanically ventilated children with RSV Source: Reuters Industry Breifing Date: May 26, 2003
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Dexamethasone benefits adults with bacterial meningitis Source: Reuters Industry Breifing Date: November 13, 2002
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Genta begins phase II trial of Genasense with Thalomid, dexamethasone Source: Reuters Industry Breifing Date: September 23, 2002
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Dexamethasone may impair lower respiratory tract RSV clearance Source: Reuters Industry Breifing Date: June 28, 2002
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Early postnatal dexamethasone treatment does not compromise outcomes Source: Reuters Industry Breifing Date: June 07, 2002
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Oral dexamethasone is effective in children with mild croup Source: Reuters Industry Breifing Date: January 11, 2002
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Dexamethasone relieves acute pharyngitis pain Source: Reuters Industry Breifing Date: May 16, 2001
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Brain growth impaired in preterm infants treated with dexamethasone Source: Reuters Industry Breifing Date: February 08, 2001
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Moderate-dose dexamethasone has adverse effects in premature infants Source: Reuters Industry Breifing Date: January 10, 2001
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Itraconazole increases plasma levels and effects of dexamethasone Source: Reuters Industry Breifing Date: December 07, 2000
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Croup is effectively treated with oral dexamethasone Source: Reuters Medical News Date: December 07, 2000
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Dexamethasone may reduce tracheal sensitivity to terbutaline Source: Reuters Medical News Date: November 23, 2000
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Early postnatal dexamethasone linked to increased risk of cerebral palsy Source: Reuters Medical News Date: October 30, 2000
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Dexamethasone protects against acute, delayed chemotherapy-induced emesis Source: Reuters Medical News Date: October 24, 2000
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Dexamethasone injection effective in acute childhood asthma Source: Reuters Medical News Date: April 03, 2000
Periodicals and News
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Early dexamethasone safely protects pulmonary status in premature infants Source: Reuters Medical News Date: March 13, 2000
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Pain after tonsillectomy modestly reduced with dexamethasone Source: Reuters Medical News Date: December 22, 1999
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Dexamethasone increases risk of infection in infants with very low birth weights Source: Reuters Medical News Date: November 08, 1999
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Megestrol and dexamethasone superior to fluoxymesterone for tx of cancer anorexia/cachexia Source: Reuters Medical News Date: October 12, 1999
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Site rotation, dexamethasone reduce local toxicity of subcutaneous methadone Source: Reuters Medical News Date: August 20, 1999
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Dexamethasone alters lipid metabolism in premature infants Source: Reuters Medical News Date: August 13, 1999
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Dexamethasone treatment increases cerebral palsy risk among preterm infants Source: Reuters Medical News Date: July 07, 1999
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Dexamethasone an effective anti-emetic in abdominal radiotherapy Source: Reuters Medical News Date: October 06, 1998
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Bacterial killing by neutrophils variably affected by dexamethasone Source: Reuters Medical News Date: September 10, 1998
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Budesonide not superior to dexamethasone in the treatment of croup Source: Reuters Medical News Date: August 20, 1998
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Dexamethasone combined with antiandrogen prolongs remission of hirsutism Source: Reuters Medical News Date: June 24, 1998
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Dexamethasone premedication decreases paclitaxel reactions Source: Reuters Medical News Date: June 11, 1998
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The NIH Within MEDLINEplus, the NIH has made an agreement with the New York Times Syndicate, the AP News Service, and Reuters to deliver news that can be browsed by the public. Search news releases at http://www.nlm.nih.gov/medlineplus/alphanews_a.html. MEDLINEplus allows you to browse across an alphabetical index. Or you can search by date at the following Web page: http://www.nlm.nih.gov/medlineplus/newsbydate.html. Often, news items are indexed by MEDLINEplus within its search engine.
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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 “dexamethasone” (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 “dexamethasone” (or synonyms). If you know the name of a company that is relevant to dexamethasone, 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 “dexamethasone” (or synonyms).
Newsletter Articles Use the Combined Health Information Database, and limit your search criteria to “newsletter articles.” Again, you will need to use the “Detailed Search” option. Go directly to the following hyperlink: http://chid.nih.gov/detail/detail.html. Go to the bottom of the search page where “You may refine your search by.” Select the dates and language that you prefer. For the format option, select “Newsletter Article.” Type “dexamethasone” (or synonyms) into the “For these words:” box. You should check back periodically with this database as it is updated every three months. The following is a typical result when searching for newsletter articles on dexamethasone:
Periodicals and News
•
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Excess Cortisol in Patients With Alzheimer's Disease Source: Mount Sinai Medical Center Alzheimer's Disease Research Center. [Newsletter] 2(1): 2-3. Spring 1991. Contact: Available from Mount Sinai Medical Center Alzheimer's Disease Research Center. Box 1230, One Gustave L. Levy Place, New York, NY 10029-6574. (212) 241-8329. PRICE: Free subscription. Summary: This newsletter article describes some of the ongoing research to determine whether excess cortisol plays an important role in the rate of deterioration of patients with Alzheimer's disease. Cortisol is a stress-sensitive hormone whose release from the adrenal glands is controlled by adrenocorticotrophic hormone (ACTH). Release of ACTH from the pituitary is influenced by several brain neurotransmitters. Researchers at Mount Sinai determined that some patients with Alzheimer's disease have levels of cortisol in plasma that are chronically higher than older persons without dementia. The degree of hypercortisolemia in the patients was correlated with their degree of cognitive impairment. Researchers also found that up to 50 percent of patients with Alzheimer's disease do not suppress secretion of cortisol in response to administration of a synthetic steroid dexamethasone, as elderly people without dementia do. These findings raised the possibility that elevated cortisol is not simply a result of brain degeneration in Alzheimer's disease, but actually may contribute to further deterioration by its affects on the hippocampus.
•
FDA Approves Second Device to Deliver Drugs to Inner Ear Source: On the Level. 17(1): 1, 6. Winter 2000. Contact: Available from Vestibular Disorders Association. P.O. Box 4467, Portland, OR 97208-4467. (800) 837-8428. E-mail:
[email protected]. Website: www.vestibular.org. Summary: This newsletter article reports on the recent FDA approval of a device called MicroWick, which is used to aid drug delivery to the inner ear. The device may be useful in treating Meniere's disease, sudden viral deafness, and autoimmune inner ear disease (AIED). MicroWick delivers medications such as dexamethasone or gentamicin to the inner ear via the round window, a membrane covered opening between the inner ear and middle ear. MicroWick is a 9mm by 1mm piece of polyvinyl acetate that is inserted into the ear by an ear surgeon during a simple office procedure. The outer end of the MicroWick protrudes slightly through a ventilation tube into the ear canal. Over the next couple of weeks, the patient drops a liquid medication prescribed by a neurotologist into the ear canal. The article includes 2 references for readers wishing additional information. 2 references.
Academic Periodicals covering Dexamethasone Numerous periodicals are currently indexed within the National Library of Medicine’s PubMed database that are known to publish articles relating to dexamethasone. In addition to these sources, you can search for articles covering dexamethasone 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.”
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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 dexamethasone. One such source is the United States Pharmacopeia. In 1820, eleven physicians met in Washington, D.C. to establish the first compendium of standard drugs for the United States. They called this compendium the U.S. Pharmacopeia (USP). Today, the USP is a non-profit organization consisting of 800 volunteer scientists, eleven elected officials, and 400 representatives of state associations and colleges of medicine and pharmacy. The USP is located in Rockville, Maryland, and its home page is located at http://www.usp.org/. The USP currently provides standards for over 3,700 medications. The resulting USP DI® Advice for the Patient® can be accessed through the National Library of Medicine of the National Institutes of Health. The database is partially derived from lists of federally approved medications in the Food and Drug Administration’s (FDA) Drug Approvals database, located at http://www.fda.gov/cder/da/da.htm. While the FDA database is rather large and difficult to navigate, the Phamacopeia is both user-friendly and free to use. It covers more than 9,000 prescription and over-the-counter medications. To access this database, simply type the following hyperlink into your Web browser: http://www.nlm.nih.gov/medlineplus/druginformation.html. To view examples of a given medication (brand names, category, description, preparation, proper use, precautions, side effects, etc.), simply follow the hyperlinks indicated within the United States Pharmacopeia (USP). Below, we have compiled a list of medications associated with dexamethasone. 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 dexamethasone: Corticosteroids •
Inhalation - U.S. Brands: AeroBid; AeroBid-M; Azmacort; Beclovent; Decadron Respihaler; Pulmicort Respules; Pulmicort Turbuhaler; Vanceril; Vanceril 84 mcg Double Strength http://www.nlm.nih.gov/medlineplus/druginfo/uspdi/202011.html
•
Nasal - U.S. Brands: Beconase; Beconase AQ; Dexacort Turbinaire; Flonase; Nasacort; Nasacort AQ; Nasalide; Nasarel; Nasonex; Rhinocort; Vancenase; Vancenase AQ 84 mcg; Vancenase pockethaler http://www.nlm.nih.gov/medlineplus/druginfo/uspdi/202012.html
•
Ophthalmic - U.S. Brands: AK-Dex; AK-Pred; AK-Tate; Baldex; Decadron; Dexair; Dexotic; Econopred; Econopred Plus; Eflone; Flarex; Fluor-Op; FML Forte; FML Liquifilm; FML S.O.P.; HMS Liquifilm; Inflamase Forte; Inflamase Mild; I-Pred; Lite Pred; Maxidex; Ocu-Dex; Ocu-Pred http://www.nlm.nih.gov/medlineplus/druginfo/uspdi/202013.html
•
Otic - U.S. Brands: Decadron http://www.nlm.nih.gov/medlineplus/druginfo/uspdi/202014.html
Corticosteroids Glucocorticoid Effects •
Systemic - U.S. Brands: Acetocot; A-hydroCort; Amcort; A-MethaPred; Aristocort; Aristocort Forte; Aristopak; Aristospan; Articulose-50; ArticuloseL.A.; Celestone; Celestone Phosphate; Celestone Soluspan; Cinalone 40; Cinonide 40; Clinacort; Clinalog; Cordrol; Cortastat http://www.nlm.nih.gov/medlineplus/druginfo/uspdi/202018.html
Corticosteroids Low Potency •
Topical - U.S. Brands: 9-1-1; Aclovate; Acticort 100; Aeroseb-Dex; Aeroseb-HC; Ala-Cort; Ala-Scalp HP; Allercort; Alphaderm; Bactine; Beta-HC; CaldeCORT Anti-Itch; CaldeCORT Light; Carmol-HC; Cetacort; Cloderm; Cortaid; CortDome; Cortef Feminine Itch; Corticaine; Cortifair http://www.nlm.nih.gov/medlineplus/druginfo/uspdi/202907.html
Docetaxel •
Systemic - U.S. Brands: Taxotere http://www.nlm.nih.gov/medlineplus/druginfo/uspdi/202920.html
Tobramycin and Dexamethasone •
Ophthalmic - U.S. Brands: Tobradex http://www.nlm.nih.gov/medlineplus/druginfo/uspdi/203776.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.
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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
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National Institute of General Medical Sciences (NIGMS); fact sheets available at http://www.nigms.nih.gov/news/facts/
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National Library of Medicine (NLM); extensive encyclopedia (A.D.A.M., Inc.) with guidelines: http://www.nlm.nih.gov/medlineplus/healthtopics.html
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National Cancer Institute (NCI); guidelines available at http://www.cancer.gov/cancerinfo/list.aspx?viewid=5f35036e-5497-4d86-8c2c714a9f7c8d25
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National Eye Institute (NEI); guidelines available at http://www.nei.nih.gov/order/index.htm
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National Heart, Lung, and Blood Institute (NHLBI); guidelines available at http://www.nhlbi.nih.gov/guidelines/index.htm
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National Human Genome Research Institute (NHGRI); research available at http://www.genome.gov/page.cfm?pageID=10000375
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National Institute on Aging (NIA); guidelines available at http://www.nia.nih.gov/health/
12
These publications are typically written by one or more of the various NIH Institutes.
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National Institute on Alcohol Abuse and Alcoholism (NIAAA); guidelines available at http://www.niaaa.nih.gov/publications/publications.htm
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National Institute of Allergy and Infectious Diseases (NIAID); guidelines available at http://www.niaid.nih.gov/publications/
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National Institute of Arthritis and Musculoskeletal and Skin Diseases (NIAMS); fact sheets and guidelines available at http://www.niams.nih.gov/hi/index.htm
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National Institute of Child Health and Human Development (NICHD); guidelines available at http://www.nichd.nih.gov/publications/pubskey.cfm
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National Institute on Deafness and Other Communication Disorders (NIDCD); fact sheets and guidelines at http://www.nidcd.nih.gov/health/
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National Institute of Dental and Craniofacial Research (NIDCR); guidelines available at http://www.nidr.nih.gov/health/
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National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK); guidelines available at http://www.niddk.nih.gov/health/health.htm
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National Institute on Drug Abuse (NIDA); guidelines available at http://www.nida.nih.gov/DrugAbuse.html
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National Institute of Environmental Health Sciences (NIEHS); environmental health information available at http://www.niehs.nih.gov/external/facts.htm
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National Institute of Mental Health (NIMH); guidelines available at http://www.nimh.nih.gov/practitioners/index.cfm
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National Institute of Neurological Disorders and Stroke (NINDS); neurological disorder information pages available at http://www.ninds.nih.gov/health_and_medical/disorder_index.htm
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National Institute of Nursing Research (NINR); publications on selected illnesses at http://www.nih.gov/ninr/news-info/publications.html
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National Institute of Biomedical Imaging and Bioengineering; general information at http://grants.nih.gov/grants/becon/becon_info.htm
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Center for Information Technology (CIT); referrals to other agencies based on keyword searches available at http://kb.nih.gov/www_query_main.asp
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National Center for Complementary and Alternative Medicine (NCCAM); health information available at http://nccam.nih.gov/health/
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National Center for Research Resources (NCRR); various information directories available at http://www.ncrr.nih.gov/publications.asp
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Office of Rare Diseases; various fact sheets available at http://rarediseases.info.nih.gov/html/resources/rep_pubs.html
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Centers for Disease Control and Prevention; various fact sheets on infectious diseases available at http://www.cdc.gov/publications.htm
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NIH Databases In addition to the various Institutes of Health that publish professional guidelines, the NIH has designed a number of databases for professionals.13 Physician-oriented resources provide a wide variety of information related to the biomedical and health sciences, both past and present. The format of these resources varies. Searchable databases, bibliographic citations, full-text articles (when available), archival collections, and images are all available. The following are referenced by the National Library of Medicine:14 •
Bioethics: Access to published literature on the ethical, legal, and public policy issues surrounding healthcare and biomedical research. This information is provided in conjunction with the Kennedy Institute of Ethics located at Georgetown University, Washington, D.C.: http://www.nlm.nih.gov/databases/databases_bioethics.html
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HIV/AIDS Resources: Describes various links and databases dedicated to HIV/AIDS research: http://www.nlm.nih.gov/pubs/factsheets/aidsinfs.html
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NLM Online Exhibitions: Describes “Exhibitions in the History of Medicine”: http://www.nlm.nih.gov/exhibition/exhibition.html. Additional resources for historical scholarship in medicine: http://www.nlm.nih.gov/hmd/hmd.html
•
Biotechnology Information: Access to public databases. The National Center for Biotechnology Information conducts research in computational biology, develops software tools for analyzing genome data, and disseminates biomedical information for the better understanding of molecular processes affecting human health and disease: http://www.ncbi.nlm.nih.gov/
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Population Information: The National Library of Medicine provides access to worldwide coverage of population, family planning, and related health issues, including family planning technology and programs, fertility, and population law and policy: http://www.nlm.nih.gov/databases/databases_population.html
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Cancer Information: Access to cancer-oriented databases: http://www.nlm.nih.gov/databases/databases_cancer.html
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Profiles in Science: Offering the archival collections of prominent twentieth-century biomedical scientists to the public through modern digital technology: http://www.profiles.nlm.nih.gov/
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Chemical Information: Provides links to various chemical databases and references: http://sis.nlm.nih.gov/Chem/ChemMain.html
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Clinical Alerts: Reports the release of findings from the NIH-funded clinical trials where such release could significantly affect morbidity and mortality: http://www.nlm.nih.gov/databases/alerts/clinical_alerts.html
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Space Life Sciences: Provides links and information to space-based research (including NASA): http://www.nlm.nih.gov/databases/databases_space.html
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MEDLINE: Bibliographic database covering the fields of medicine, nursing, dentistry, veterinary medicine, the healthcare system, and the pre-clinical sciences: http://www.nlm.nih.gov/databases/databases_medline.html
13
Remember, for the general public, the National Library of Medicine recommends the databases referenced in MEDLINEplus (http://medlineplus.gov/ or http://www.nlm.nih.gov/medlineplus/databases.html). 14 See http://www.nlm.nih.gov/databases/databases.html.
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Toxicology and Environmental Health Information (TOXNET): Databases covering toxicology and environmental health: http://sis.nlm.nih.gov/Tox/ToxMain.html
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Visible Human Interface: Anatomically detailed, three-dimensional representations of normal male and female human bodies: http://www.nlm.nih.gov/research/visible/visible_human.html
The NLM 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 “dexamethasone” (or synonyms) into the search box and click “Search.” The results will be presented in a tabular form, indicating the number of references in each database category. Results Summary Category Journal Articles Books / Periodicals / Audio Visual Consumer Health Meeting Abstracts Other Collections Total
Items Found 39789 87 1066 61 160 41163
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 “dexamethasone” (or synonyms) at the following Web site: http://text.nlm.nih.gov.
15
Adapted from NLM: http://gateway.nlm.nih.gov/gw/Cmd?Overview.x.
16
The NLM Gateway is currently being developed by the Lister Hill National Center for Biomedical Communications (LHNCBC) at the National Library of Medicine (NLM) of the National Institutes of Health (NIH). 17 Adapted from HSTAT: http://www.nlm.nih.gov/pubs/factsheets/hstat.html. 18 19
The HSTAT URL is http://hstat.nlm.nih.gov/.
Other important documents in HSTAT include: the National Institutes of Health (NIH) Consensus Conference Reports and Technology Assessment Reports; the HIV/AIDS Treatment Information Service (ATIS) resource documents; the Substance Abuse and Mental Health Services Administration's Center for Substance Abuse Treatment (SAMHSA/CSAT) Treatment Improvement Protocols (TIP) and Center for Substance Abuse Prevention (SAMHSA/CSAP) Prevention Enhancement Protocols System (PEPS); the Public Health Service (PHS) Preventive Services Task Force's Guide to Clinical Preventive Services; the independent, nonfederal Task Force on Community Services’ Guide to Community Preventive Services; and the Health Technology Advisory Committee (HTAC) of the Minnesota Health Care Commission (MHCC) health technology evaluations.
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Coffee Break: Tutorials for Biologists20 Coffee Break is a general healthcare site that takes a scientific view of the news and covers recent breakthroughs in biology that may one day assist physicians in developing treatments. Here you will find a collection of short reports on recent biological discoveries. Each report incorporates interactive tutorials that demonstrate how bioinformatics tools are used as a part of the research process. Currently, all Coffee Breaks are written by NCBI staff.21 Each report is about 400 words and is usually based on a discovery reported in one or more articles from recently published, peer-reviewed literature.22 This site has new articles every few weeks, so it can be considered an online magazine of sorts. It is intended for general background information. You can access the Coffee Break Web site at the following hyperlink: http://www.ncbi.nlm.nih.gov/Coffeebreak/.
Other Commercial Databases In addition to resources maintained by official agencies, other databases exist that are commercial ventures addressing medical professionals. Here are some examples that may interest you: •
CliniWeb International: Index and table of contents to selected clinical information on the Internet; see http://www.ohsu.edu/cliniweb/.
•
Medical World Search: Searches full text from thousands of selected medical sites on the Internet; see http://www.mwsearch.com/.
The Genome Project and Dexamethasone In the following section, we will discuss databases and references which relate to the Genome Project and dexamethasone. Online Mendelian Inheritance in Man (OMIM) The Online Mendelian Inheritance in Man (OMIM) database is a catalog of human genes and genetic disorders authored and edited by Dr. Victor A. McKusick and his colleagues at Johns Hopkins and elsewhere. OMIM was developed for the World Wide Web by the National Center for Biotechnology Information (NCBI).23 The database contains textual information, pictures, and reference information. It also contains copious links to NCBI’s Entrez database of MEDLINE articles and sequence information. 20 Adapted 21
from http://www.ncbi.nlm.nih.gov/Coffeebreak/Archive/FAQ.html.
The figure that accompanies each article is frequently supplied by an expert external to NCBI, in which case the source of the figure is cited. The result is an interactive tutorial that tells a biological story. 22 After a brief introduction that sets the work described into a broader context, the report focuses on how a molecular understanding can provide explanations of observed biology and lead to therapies for diseases. Each vignette is accompanied by a figure and hypertext links that lead to a series of pages that interactively show how NCBI tools and resources are used in the research process. 23 Adapted from http://www.ncbi.nlm.nih.gov/. Established in 1988 as a national resource for molecular biology information, NCBI creates public databases, conducts research in computational biology, develops software tools for analyzing genome data, and disseminates biomedical information--all for the better understanding of molecular processes affecting human health and disease.
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To search the database, go to http://www.ncbi.nlm.nih.gov/Omim/searchomim.html. Type “dexamethasone” (or synonyms) into the search box, and click “Submit Search.” If too many results appear, you can narrow the search by adding the word “clinical.” Each report will have additional links to related research and databases. In particular, the option “Database Links” will search across technical databases that offer an abundance of information. The following is an example of the results you can obtain from the OMIM for dexamethasone: •
RAS Protein, Dexamethasone-induced, 1 Web site: http://www.ncbi.nlm.nih.gov/entrez/dispomim.cgi?id=605550 Genes and Disease (NCBI - Map)
The Genes and Disease database is produced by the National Center for Biotechnology Information of the National Library of Medicine at the National Institutes of Health. This Web site categorizes each disorder by system of the body. Go to http://www.ncbi.nlm.nih.gov/disease/, and browse the system pages to have a full view of important conditions linked to human genes. Since this site is regularly updated, you may wish to revisit it from time to time. The following systems and associated disorders are addressed: •
Cancer: Uncontrolled cell division. Examples: Breast and ovarian cancer, Burkitt lymphoma, chronic myeloid leukemia, colon cancer, lung cancer, malignant melanoma, multiple endocrine neoplasia, neurofibromatosis, p53 tumor suppressor, pancreatic cancer, prostate cancer, Ras oncogene, RB: retinoblastoma, von Hippel-Lindau syndrome. Web site: http://www.ncbi.nlm.nih.gov/disease/Cancer.html
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Immune System: Fights invaders. Examples: Asthma, autoimmune polyglandular syndrome, Crohn’s disease, DiGeorge syndrome, familial Mediterranean fever, immunodeficiency with Hyper-IgM, severe combined immunodeficiency. Web site: http://www.ncbi.nlm.nih.gov/disease/Immune.html
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Metabolism: Food and energy. Examples: Adreno-leukodystrophy, atherosclerosis, Best disease, Gaucher disease, glucose galactose malabsorption, gyrate atrophy, juvenile-onset diabetes, obesity, paroxysmal nocturnal hemoglobinuria, phenylketonuria, Refsum disease, Tangier disease, Tay-Sachs disease. Web site: http://www.ncbi.nlm.nih.gov/disease/Metabolism.html
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Muscle and Bone: Movement and growth. Examples: Duchenne muscular dystrophy, Ellis-van Creveld syndrome, Marfan syndrome, myotonic dystrophy, spinal muscular atrophy. Web site: http://www.ncbi.nlm.nih.gov/disease/Muscle.html
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Nervous System: Mind and body. Examples: Alzheimer disease, amyotrophic lateral sclerosis, Angelman syndrome, Charcot-Marie-Tooth disease, epilepsy, essential tremor, fragile X syndrome, Friedreich’s ataxia, Huntington disease, Niemann-Pick disease, Parkinson disease, Prader-Willi syndrome, Rett syndrome, spinocerebellar atrophy, Williams syndrome. Web site: http://www.ncbi.nlm.nih.gov/disease/Brain.html
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Signals: Cellular messages. Examples: Ataxia telangiectasia, Cockayne syndrome, glaucoma, male-patterned baldness, SRY: sex determination, tuberous sclerosis, Waardenburg syndrome, Werner syndrome. Web site: http://www.ncbi.nlm.nih.gov/disease/Signals.html
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Transporters: Pumps and channels. Examples: Cystic fibrosis, deafness, diastrophic dysplasia, Hemophilia A, long-QT syndrome, Menkes syndrome, Pendred syndrome, polycystic kidney disease, sickle cell anemia, Wilson’s disease, Zellweger syndrome. Web site: http://www.ncbi.nlm.nih.gov/disease/Transporters.html Entrez
Entrez is a search and retrieval system that integrates several linked databases at the National Center for Biotechnology Information (NCBI). These databases include nucleotide sequences, protein sequences, macromolecular structures, whole genomes, and MEDLINE through PubMed. Entrez provides access to the following databases: •
3D Domains: Domains from Entrez Structure, Web site: http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=geo
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Books: Online books, Web site: http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=books
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Genome: Complete genome assemblies, Web site: http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=Genome
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NCBI’s Protein Sequence Information Survey Results: Web site: http://www.ncbi.nlm.nih.gov/About/proteinsurvey/
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Nucleotide Sequence Database (Genbank): Web site: http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=Nucleotide
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OMIM: Online Mendelian Inheritance in Man, Web site: http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=OMIM
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PopSet: Population study data sets, Web site: http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=Popset
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ProbeSet: Gene Expression Omnibus (GEO), Web site: http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=geo
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Protein Sequence Database: Web site: http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=Protein
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PubMed: Biomedical literature (PubMed), Web site: http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed
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Structure: Three-dimensional macromolecular structures, Web site: http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=Structure
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Taxonomy: Organisms in GenBank, Web site: http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=Taxonomy
To access the Entrez system at the National Center for Biotechnology Information, go to http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?CMD=search&DB=genome, and then
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select the database that you would like to search. The databases available are listed in the drop box next to “Search.” Enter “dexamethasone” (or synonyms) into the search box and click “Go.” Jablonski’s Multiple Congenital Anomaly/Mental Retardation (MCA/MR) Syndromes Database24 This online resource has been developed to facilitate the identification and differentiation of syndromic entities. Special attention is given to the type of information that is usually limited or completely omitted in existing reference sources due to space limitations of the printed form. At http://www.nlm.nih.gov/mesh/jablonski/syndrome_toc/toc_a.html, you can search across syndromes using an alphabetical index. Search by keywords at http://www.nlm.nih.gov/mesh/jablonski/syndrome_db.html.
The Genome Database25 Established at Johns Hopkins University in Baltimore, Maryland in 1990, the Genome Database (GDB) is the official central repository for genomic mapping data resulting from the Human Genome Initiative. In the spring of 1999, the Bioinformatics Supercomputing Centre (BiSC) at the Hospital for Sick Children in Toronto, Ontario assumed the management of GDB. The Human Genome Initiative is a worldwide research effort focusing on structural analysis of human DNA to determine the location and sequence of the estimated 100,000 human genes. In support of this project, GDB stores and curates data generated by researchers worldwide who are engaged in the mapping effort of the Human Genome Project (HGP). GDB’s mission is to provide scientists with an encyclopedia of the human genome which is continually revised and updated to reflect the current state of scientific knowledge. Although GDB has historically focused on gene mapping, its focus will broaden as the Genome Project moves from mapping to sequence, and finally, to functional analysis. To access the GDB, simply go to the following hyperlink: http://www.gdb.org/. Search “All Biological Data” by “Keyword.” Type “dexamethasone” (or synonyms) into the search box, and review the results. If more than one word is used in the search box, then separate each one with the word “and” or “or” (using “or” might be useful when using synonyms).
24
Adapted from the National Library of Medicine: http://www.nlm.nih.gov/mesh/jablonski/about_syndrome.html. 25 Adapted from the Genome Database: http://gdbwww.gdb.org/gdb/aboutGDB.html - mission.
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APPENDIX B. PATIENT RESOURCES Overview Official agencies, as well as federally funded institutions supported by national grants, frequently publish a variety of guidelines written with the patient in mind. These are typically called “Fact Sheets” or “Guidelines.” They can take the form of a brochure, information kit, pamphlet, or flyer. Often they are only a few pages in length. Since new guidelines on dexamethasone 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 dexamethasone. 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 dexamethasone. 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 “dexamethasone”:
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Other guides Asthma http://www.nlm.nih.gov/medlineplus/asthma.html Crohn's Disease http://www.nlm.nih.gov/medlineplus/crohnsdisease.html Eczema http://www.nlm.nih.gov/medlineplus/eczema.html Lupus http://www.nlm.nih.gov/medlineplus/lupus.html Ulcerative Colitis http://www.nlm.nih.gov/medlineplus/ulcerativecolitis.html
You may also choose to use the search utility provided by MEDLINEplus at the following Web address: http://www.nlm.nih.gov/medlineplus/. Simply type a keyword into the search box and click “Search.” This utility is similar to the NIH search utility, with the exception that it only includes materials that are linked within the MEDLINEplus system (mostly patient-oriented information). It also has the disadvantage of generating unstructured results. We recommend, therefore, that you use this method only if you have a very targeted search. The NIH Search Utility The NIH search utility allows you to search for documents on over 100 selected Web sites that comprise the NIH-WEB-SPACE. Each of these servers is “crawled” and indexed on an ongoing basis. Your search will produce a list of various documents, all of which will relate in some way to dexamethasone. The drawbacks of this approach are that the information is not organized by theme and that the references are often a mix of information for professionals and patients. Nevertheless, a large number of the listed Web sites provide useful background information. We can only recommend this route, therefore, for relatively rare or specific disorders, or when using highly targeted searches. To use the NIH search utility, visit the following Web page: http://search.nih.gov/index.html. Additional Web Sources A number of Web sites are available to the public that often link to government sites. These can also point you in the direction of essential information. The following is a representative sample: •
AOL: http://search.aol.com/cat.adp?id=168&layer=&from=subcats
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Family Village: http://www.familyvillage.wisc.edu/specific.htm
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Google: http://directory.google.com/Top/Health/Conditions_and_Diseases/
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Med Help International: http://www.medhelp.org/HealthTopics/A.html
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Open Directory Project: http://dmoz.org/Health/Conditions_and_Diseases/
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Yahoo.com: http://dir.yahoo.com/Health/Diseases_and_Conditions/
Patient Resources
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WebMD®Health: http://my.webmd.com/health_topics
Finding Associations There are several Internet directories that provide lists of medical associations with information on or resources relating to dexamethasone. By consulting all of associations listed in this chapter, you will have nearly exhausted all sources for patient associations concerned with dexamethasone. 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 dexamethasone. 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 “dexamethasone” (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 “dexamethasone”. Type the following hyperlink into your Web browser: http://chid.nih.gov/detail/detail.html. To find associations, use the drop boxes at the bottom of the search page where “You may refine your search by.” For publication date, select “All Years.” Then, select your preferred language and the format option “Organization Resource Sheet.” Type “dexamethasone” (or synonyms) into the “For these words:” box. You should check back periodically with this database since it is updated every three months.
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The National Organization for Rare Disorders, Inc. The National Organization for Rare Disorders, Inc. has prepared a Web site that provides, at no charge, lists of associations organized by health topic. You can access this database at the following Web site: http://www.rarediseases.org/search/orgsearch.html. Type “dexamethasone” (or a synonym) into the search box, and click “Submit Query.”
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APPENDIX C. FINDING MEDICAL LIBRARIES Overview In this Appendix, we show you how to quickly find a medical library in your area.
Preparation Your local public library and medical libraries have interlibrary loan programs with the National Library of Medicine (NLM), one of the largest medical collections in the world. According to the NLM, most of the literature in the general and historical collections of the National Library of Medicine is available on interlibrary loan to any library. If you would like to access NLM medical literature, then visit a library in your area that can request the publications for you.26
Finding a Local Medical Library The quickest method to locate medical libraries is to use the Internet-based directory published by the National Network of Libraries of Medicine (NN/LM). This network includes 4626 members and affiliates that provide many services to librarians, health professionals, and the public. To find a library in your area, simply visit http://nnlm.gov/members/adv.html or call 1-800-338-7657.
Medical Libraries in the U.S. and Canada In addition to the NN/LM, the National Library of Medicine (NLM) lists a number of libraries with reference facilities that are open to the public. The following is the NLM’s list and includes hyperlinks to each library’s Web site. These Web pages can provide information on hours of operation and other restrictions. The list below is a small sample of
26
Adapted from the NLM: http://www.nlm.nih.gov/psd/cas/interlibrary.html.
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libraries recommended by the National Library of Medicine (sorted alphabetically by name of the U.S. state or Canadian province where the library is located)27: •
Alabama: Health InfoNet of Jefferson County (Jefferson County Library Cooperative, Lister Hill Library of the Health Sciences), http://www.uab.edu/infonet/
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Alabama: Richard M. Scrushy Library (American Sports Medicine Institute)
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Arizona: Samaritan Regional Medical Center: The Learning Center (Samaritan Health System, Phoenix, Arizona), http://www.samaritan.edu/library/bannerlibs.htm
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California: Kris Kelly Health Information Center (St. Joseph Health System, Humboldt), http://www.humboldt1.com/~kkhic/index.html
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California: Community Health Library of Los Gatos, http://www.healthlib.org/orgresources.html
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California: Consumer Health Program and Services (CHIPS) (County of Los Angeles Public Library, Los Angeles County Harbor-UCLA Medical Center Library) - Carson, CA, http://www.colapublib.org/services/chips.html
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California: Gateway Health Library (Sutter Gould Medical Foundation)
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California: Health Library (Stanford University Medical Center), http://wwwmed.stanford.edu/healthlibrary/
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California: Patient Education Resource Center - Health Information and Resources (University of California, San Francisco), http://sfghdean.ucsf.edu/barnett/PERC/default.asp
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California: Redwood Health Library (Petaluma Health Care District), http://www.phcd.org/rdwdlib.html
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California: Los Gatos PlaneTree Health Library, http://planetreesanjose.org/
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California: Sutter Resource Library (Sutter Hospitals Foundation, Sacramento), http://suttermedicalcenter.org/library/
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California: Health Sciences Libraries (University of California, Davis), http://www.lib.ucdavis.edu/healthsci/
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California: ValleyCare Health Library & Ryan Comer Cancer Resource Center (ValleyCare Health System, Pleasanton), http://gaelnet.stmarysca.edu/other.libs/gbal/east/vchl.html
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California: Washington Community Health Resource Library (Fremont), http://www.healthlibrary.org/
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Colorado: William V. Gervasini Memorial Library (Exempla Healthcare), http://www.saintjosephdenver.org/yourhealth/libraries/
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Connecticut: Hartford Hospital Health Science Libraries (Hartford Hospital), http://www.harthosp.org/library/
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Connecticut: Healthnet: Connecticut Consumer Health Information Center (University of Connecticut Health Center, Lyman Maynard Stowe Library), http://library.uchc.edu/departm/hnet/
27
Abstracted from http://www.nlm.nih.gov/medlineplus/libraries.html.
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Connecticut: Waterbury Hospital Health Center Library (Waterbury Hospital, Waterbury), http://www.waterburyhospital.com/library/consumer.shtml
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Delaware: Consumer Health Library (Christiana Care Health System, Eugene du Pont Preventive Medicine & Rehabilitation Institute, Wilmington), http://www.christianacare.org/health_guide/health_guide_pmri_health_info.cfm
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Delaware: Lewis B. Flinn Library (Delaware Academy of Medicine, Wilmington), http://www.delamed.org/chls.html
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Georgia: Family Resource Library (Medical College of Georgia, Augusta), http://cmc.mcg.edu/kids_families/fam_resources/fam_res_lib/frl.htm
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Georgia: Health Resource Center (Medical Center of Central Georgia, Macon), http://www.mccg.org/hrc/hrchome.asp
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Hawaii: Hawaii Medical Library: Consumer Health Information Service (Hawaii Medical Library, Honolulu), http://hml.org/CHIS/
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Idaho: DeArmond Consumer Health Library (Kootenai Medical Center, Coeur d’Alene), http://www.nicon.org/DeArmond/index.htm
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Illinois: Health Learning Center of Northwestern Memorial Hospital (Chicago), http://www.nmh.org/health_info/hlc.html
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Illinois: Medical Library (OSF Saint Francis Medical Center, Peoria), http://www.osfsaintfrancis.org/general/library/
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Kentucky: Medical Library - Services for Patients, Families, Students & the Public (Central Baptist Hospital, Lexington), http://www.centralbap.com/education/community/library.cfm
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Kentucky: University of Kentucky - Health Information Library (Chandler Medical Center, Lexington), http://www.mc.uky.edu/PatientEd/
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Louisiana: Alton Ochsner Medical Foundation Library (Alton Ochsner Medical Foundation, New Orleans), http://www.ochsner.org/library/
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Louisiana: Louisiana State University Health Sciences Center Medical LibraryShreveport, http://lib-sh.lsuhsc.edu/
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Maine: Franklin Memorial Hospital Medical Library (Franklin Memorial Hospital, Farmington), http://www.fchn.org/fmh/lib.htm
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Maine: Gerrish-True Health Sciences Library (Central Maine Medical Center, Lewiston), http://www.cmmc.org/library/library.html
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Maine: Hadley Parrot Health Science Library (Eastern Maine Healthcare, Bangor), http://www.emh.org/hll/hpl/guide.htm
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Maine: Maine Medical Center Library (Maine Medical Center, Portland), http://www.mmc.org/library/
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Maine: Parkview Hospital (Brunswick), http://www.parkviewhospital.org/
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Maine: Southern Maine Medical Center Health Sciences Library (Southern Maine Medical Center, Biddeford), http://www.smmc.org/services/service.php3?choice=10
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Maine: Stephens Memorial Hospital’s Health Information Library (Western Maine Health, Norway), http://www.wmhcc.org/Library/
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Manitoba, Canada: Consumer & Patient Health Information Service (University of Manitoba Libraries), http://www.umanitoba.ca/libraries/units/health/reference/chis.html
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Manitoba, Canada: J.W. Crane Memorial Library (Deer Lodge Centre, Winnipeg), http://www.deerlodge.mb.ca/crane_library/about.asp
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Maryland: Health Information Center at the Wheaton Regional Library (Montgomery County, Dept. of Public Libraries, Wheaton Regional Library), http://www.mont.lib.md.us/healthinfo/hic.asp
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Massachusetts: Baystate Medical Center Library (Baystate Health System), http://www.baystatehealth.com/1024/
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Massachusetts: Boston University Medical Center Alumni Medical Library (Boston University Medical Center), http://med-libwww.bu.edu/library/lib.html
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Massachusetts: Lowell General Hospital Health Sciences Library (Lowell General Hospital, Lowell), http://www.lowellgeneral.org/library/HomePageLinks/WWW.htm
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Massachusetts: Paul E. Woodard Health Sciences Library (New England Baptist Hospital, Boston), http://www.nebh.org/health_lib.asp
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Massachusetts: St. Luke’s Hospital Health Sciences Library (St. Luke’s Hospital, Southcoast Health System, New Bedford), http://www.southcoast.org/library/
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Massachusetts: Treadwell Library Consumer Health Reference Center (Massachusetts General Hospital), http://www.mgh.harvard.edu/library/chrcindex.html
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Massachusetts: UMass HealthNet (University of Massachusetts Medical School, Worchester), http://healthnet.umassmed.edu/
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Michigan: Botsford General Hospital Library - Consumer Health (Botsford General Hospital, Library & Internet Services), http://www.botsfordlibrary.org/consumer.htm
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Michigan: Helen DeRoy Medical Library (Providence Hospital and Medical Centers), http://www.providence-hospital.org/library/
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Michigan: Marquette General Hospital - Consumer Health Library (Marquette General Hospital, Health Information Center), http://www.mgh.org/center.html
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Michigan: Patient Education Resouce Center - University of Michigan Cancer Center (University of Michigan Comprehensive Cancer Center, Ann Arbor), http://www.cancer.med.umich.edu/learn/leares.htm
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Michigan: Sladen Library & Center for Health Information Resources - Consumer Health Information (Detroit), http://www.henryford.com/body.cfm?id=39330
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Montana: Center for Health Information (St. Patrick Hospital and Health Sciences Center, Missoula)
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National: Consumer Health Library Directory (Medical Library Association, Consumer and Patient Health Information Section), http://caphis.mlanet.org/directory/index.html
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National: National Network of Libraries of Medicine (National Library of Medicine) provides library services for health professionals in the United States who do not have access to a medical library, http://nnlm.gov/
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National: NN/LM List of Libraries Serving the Public (National Network of Libraries of Medicine), http://nnlm.gov/members/
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Nevada: Health Science Library, West Charleston Library (Las Vegas-Clark County Library District, Las Vegas), http://www.lvccld.org/special_collections/medical/index.htm
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New Hampshire: Dartmouth Biomedical Libraries (Dartmouth College Library, Hanover), http://www.dartmouth.edu/~biomed/resources.htmld/conshealth.htmld/
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New Jersey: Consumer Health Library (Rahway Hospital, Rahway), http://www.rahwayhospital.com/library.htm
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New Jersey: Dr. Walter Phillips Health Sciences Library (Englewood Hospital and Medical Center, Englewood), http://www.englewoodhospital.com/links/index.htm
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New Jersey: Meland Foundation (Englewood Hospital and Medical Center, Englewood), http://www.geocities.com/ResearchTriangle/9360/
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New York: Choices in Health Information (New York Public Library) - NLM Consumer Pilot Project participant, http://www.nypl.org/branch/health/links.html
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New York: Health Information Center (Upstate Medical University, State University of New York, Syracuse), http://www.upstate.edu/library/hic/
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New York: Health Sciences Library (Long Island Jewish Medical Center, New Hyde Park), http://www.lij.edu/library/library.html
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New York: ViaHealth Medical Library (Rochester General Hospital), http://www.nyam.org/library/
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Ohio: Consumer Health Library (Akron General Medical Center, Medical & Consumer Health Library), http://www.akrongeneral.org/hwlibrary.htm
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Oklahoma: The Health Information Center at Saint Francis Hospital (Saint Francis Health System, Tulsa), http://www.sfh-tulsa.com/services/healthinfo.asp
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Oregon: Planetree Health Resource Center (Mid-Columbia Medical Center, The Dalles), http://www.mcmc.net/phrc/
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Pennsylvania: Community Health Information Library (Milton S. Hershey Medical Center, Hershey), http://www.hmc.psu.edu/commhealth/
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Pennsylvania: Community Health Resource Library (Geisinger Medical Center, Danville), http://www.geisinger.edu/education/commlib.shtml
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Pennsylvania: HealthInfo Library (Moses Taylor Hospital, Scranton), http://www.mth.org/healthwellness.html
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Pennsylvania: Hopwood Library (University of Pittsburgh, Health Sciences Library System, Pittsburgh), http://www.hsls.pitt.edu/guides/chi/hopwood/index_html
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Pennsylvania: Koop Community Health Information Center (College of Physicians of Philadelphia), http://www.collphyphil.org/kooppg1.shtml
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Pennsylvania: Learning Resources Center - Medical Library (Susquehanna Health System, Williamsport), http://www.shscares.org/services/lrc/index.asp
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Pennsylvania: Medical Library (UPMC Health System, Pittsburgh), http://www.upmc.edu/passavant/library.htm
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Quebec, Canada: Medical Library (Montreal General Hospital), http://www.mghlib.mcgill.ca/
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South Dakota: Rapid City Regional Hospital Medical Library (Rapid City Regional Hospital), http://www.rcrh.org/Services/Library/Default.asp
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Texas: Houston HealthWays (Houston Academy of Medicine-Texas Medical Center Library), http://hhw.library.tmc.edu/
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Washington: Community Health Library (Kittitas Valley Community Hospital), http://www.kvch.com/
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Washington: Southwest Washington Medical Center Library (Southwest Washington Medical Center, Vancouver), http://www.swmedicalcenter.com/body.cfm?id=72
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ONLINE GLOSSARIES The Internet provides access to a number of free-to-use medical dictionaries. The National Library of Medicine has compiled the following list of online dictionaries: •
ADAM Medical Encyclopedia (A.D.A.M., Inc.), comprehensive medical reference: http://www.nlm.nih.gov/medlineplus/encyclopedia.html
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MedicineNet.com Medical Dictionary (MedicineNet, Inc.): http://www.medterms.com/Script/Main/hp.asp
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Merriam-Webster Medical Dictionary (Inteli-Health, Inc.): http://www.intelihealth.com/IH/
•
Multilingual Glossary of Technical and Popular Medical Terms in Eight European Languages (European Commission) - Danish, Dutch, English, French, German, Italian, Portuguese, and Spanish: http://allserv.rug.ac.be/~rvdstich/eugloss/welcome.html
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On-line Medical Dictionary (CancerWEB): http://cancerweb.ncl.ac.uk/omd/
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Rare Diseases Terms (Office of Rare Diseases): http://ord.aspensys.com/asp/diseases/diseases.asp
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Technology Glossary (National Library of Medicine) - Health Care Technology: http://www.nlm.nih.gov/nichsr/ta101/ta10108.htm
Beyond these, MEDLINEplus contains a very patient-friendly encyclopedia covering every aspect of medicine (licensed from A.D.A.M., Inc.). The ADAM Medical Encyclopedia can be accessed at http://www.nlm.nih.gov/medlineplus/encyclopedia.html. ADAM is also available on commercial Web sites such as drkoop.com (http://www.drkoop.com/) and Web MD (http://my.webmd.com/adam/asset/adam_disease_articles/a_to_z/a). The NIH suggests the following Web sites in the ADAM Medical Encyclopedia when searching for information on dexamethasone: •
Basic Guidelines for Dexamethasone Dexamethasone suppression test Web site: http://www.nlm.nih.gov/medlineplus/ency/article/003694.htm
•
Signs & Symptoms for Dexamethasone Fainting Web site: http://www.nlm.nih.gov/medlineplus/ency/article/003092.htm Stress Web site: http://www.nlm.nih.gov/medlineplus/ency/article/003211.htm
•
Diagnostics and Tests for Dexamethasone ACTH Web site: http://www.nlm.nih.gov/medlineplus/ency/article/003695.htm Cortisol measurement Web site: http://www.nlm.nih.gov/medlineplus/ency/article/003693.htm
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Venipuncture Web site: http://www.nlm.nih.gov/medlineplus/ency/article/003423.htm •
Background Topics for Dexamethasone Adolescent test or procedure preparation Web site: http://www.nlm.nih.gov/medlineplus/ency/article/002054.htm Adrenal glands Web site: http://www.nlm.nih.gov/medlineplus/ency/article/002219.htm Bleeding Web site: http://www.nlm.nih.gov/medlineplus/ency/article/000045.htm Infant test or procedure preparation Web site: http://www.nlm.nih.gov/medlineplus/ency/article/002055.htm Preschooler test or procedure preparation Web site: http://www.nlm.nih.gov/medlineplus/ency/article/002057.htm Schoolage test or procedure preparation Web site: http://www.nlm.nih.gov/medlineplus/ency/article/002058.htm Toddler test or procedure preparation Web site: http://www.nlm.nih.gov/medlineplus/ency/article/002056.htm
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
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MEL-Michigan Electronic Library List of Online Health and Medical Dictionaries (Michigan Electronic Library): http://mel.lib.mi.us/health/health-dictionaries.html
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Patient Education: Glossaries (DMOZ Open Directory Project): http://dmoz.org/Health/Education/Patient_Education/Glossaries/
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Web of Online Dictionaries (Bucknell University): http://www.yourdictionary.com/diction5.html#medicine
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DEXAMETHASONE 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] Ablation: The removal of an organ by surgery. [NIH] Acantholysis: Separation of the prickle cells of the stratum spinosum of the epidermis, resulting in atrophy of the prickle cell layer. It is seen in diseases such as pemphigus vulgaris (see pemphigus) and keratosis follicularis. [NIH] 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] Acetone: A colorless liquid used as a solvent and an antiseptic. It is one of the ketone bodies produced during ketoacidosis. [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] Acetylglucosamine: The N-acetyl derivative of glucosamine. [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] Acquired Immunodeficiency Syndrome: An acquired defect of cellular immunity associated with infection by the human immunodeficiency virus (HIV), a CD4-positive Tlymphocyte count under 200 cells/microliter or less than 14% of total lymphocytes, and increased susceptibility to opportunistic infections and malignant neoplasms. Clinical manifestations also include emaciation (wasting) and dementia. These elements reflect criteria for AIDS as defined by the CDC in 1993. [NIH] Actin: Essential component of the cell skeleton. [NIH] Acute leukemia: A rapidly progressing cancer of the blood-forming tissue (bone marrow). [NIH]
Acute lymphoblastic leukemia: ALL. A quickly progressing disease in which too many immature white blood cells called lymphoblasts are found in the blood and bone marrow. Also called acute lymphocytic leukemia. [NIH] Acute lymphocytic leukemia: ALL. A quickly progressing disease in which too many
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immature white blood cells called lymphoblasts are found in the blood and bone marrow. Also called acute lymphoblastic leukemia. [NIH] Acute myelogenous leukemia: AML. A quickly progressing disease in which too many immature blood-forming cells are found in the blood and bone marrow. Also called acute myeloid leukemia or acute nonlymphocytic leukemia. [NIH] Acute myeloid leukemia: AML. A quickly progressing disease in which too many immature blood-forming cells are found in the blood and bone marrow. Also called acute myelogenous leukemia or acute nonlymphocytic leukemia. [NIH] Acute nonlymphocytic leukemia: A quickly progressing disease in which too many immature blood-forming cells are found in the blood and bone marrow. Also called acute myeloid leukemia or acute myelogenous leukemia. [NIH] 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] Adenocarcinoma: A malignant epithelial tumor with a glandular organization. [NIH] Adenosine: A nucleoside that is composed of adenine and d-ribose. Adenosine or adenosine derivatives play many important biological roles in addition to being components of DNA and RNA. Adenosine itself is a neurotransmitter. [NIH] Adipocytes: Fat-storing cells found mostly in the abdominal cavity and subcutaneous tissue. Fat is usually stored in the form of tryglycerides. [NIH] Adipose Tissue: Connective tissue composed of fat cells lodged in the meshes of areolar tissue. [NIH] Adjunctive Therapy: Another treatment used together with the primary treatment. Its purpose is to assist the primary treatment. [NIH] Adjuvant: A substance which aids another, such as an auxiliary remedy; in immunology, nonspecific stimulator (e.g., BCG vaccine) of the immune response. [EU] Adrenal Cortex: The outer layer of the adrenal gland. It secretes mineralocorticoids, androgens, and glucocorticoids. [NIH] Adrenal Glands: Paired glands situated in the retroperitoneal tissues at the superior pole of each kidney. [NIH] Adrenal Medulla: The inner part of the adrenal gland; it synthesizes, stores and releases catecholamines. [NIH] Adrenergic: Activated by, characteristic of, or secreting epinephrine or substances with similar activity; the term is applied to those nerve fibres that liberate norepinephrine at a synapse when a nerve impulse passes, i.e., the sympathetic fibres. [EU] Adrenergic Agents: Drugs that act on adrenergic receptors or affect the life cycle of adrenergic transmitters. Included here are adrenergic agonists and antagonists and agents that affect the synthesis, storage, uptake, metabolism, or release of adrenergic transmitters. [NIH]
Adverse Effect: An unwanted side effect of treatment. [NIH]
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Aerobic: In biochemistry, reactions that need oxygen to happen or happen when oxygen is present. [NIH] Aerosol: A solution of a drug which can be atomized into a fine mist for inhalation therapy. [EU]
Afferent: Concerned with the transmission of neural impulse toward the central part of the nervous system. [NIH] Afferent Pathways: Nerve structures through which impulses are conducted from a peripheral part toward a nerve center. [NIH] Affinity: 1. Inherent likeness or relationship. 2. A special attraction for a specific element, organ, or structure. 3. Chemical affinity; the force that binds atoms in molecules; the tendency of substances to combine by chemical reaction. 4. The strength of noncovalent chemical binding between two substances as measured by the dissociation constant of the complex. 5. In immunology, a thermodynamic expression of the strength of interaction between a single antigen-binding site and a single antigenic determinant (and thus of the stereochemical compatibility between them), most accurately applied to interactions among simple, uniform antigenic determinants such as haptens. Expressed as the association constant (K litres mole -1), which, owing to the heterogeneity of affinities in a population of antibody molecules of a given specificity, actually represents an average value (mean intrinsic association constant). 6. The reciprocal of the dissociation constant. [EU] Agar: A complex sulfated polymer of galactose units, extracted from Gelidium cartilagineum, Gracilaria confervoides, and related red algae. It is used as a gel in the preparation of solid culture media for microorganisms, as a bulk laxative, in making emulsions, and as a supporting medium for immunodiffusion and immunoelectrophoresis. [NIH]
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] Agoraphobia: Obsessive, persistent, intense fear of open places. [NIH] Air Pressure: The force per unit area that the air exerts on any surface in contact with it. Primarily used for articles pertaining to air pressure within a closed environment. [NIH] Airway: A device for securing unobstructed passage of air into and out of the lungs during general anesthesia. [NIH] Albumin: 1. Any protein that is soluble in water and moderately concentrated salt solutions and is coagulable by heat. 2. Serum albumin; the major plasma protein (approximately 60 per cent of the total), which is responsible for much of the plasma colloidal osmotic pressure and serves as a transport protein carrying large organic anions, such as fatty acids, bilirubin, and many drugs, and also carrying certain hormones, such as cortisol and thyroxine, when their specific binding globulins are saturated. Albumin is synthesized in the liver. Low serum levels occur in protein malnutrition, active inflammation and serious hepatic and renal disease. [EU] Aldosterone: (11 beta)-11,21-Dihydroxy-3,20-dioxopregn-4-en-18-al. A hormone secreted by the adrenal cortex that functions in the regulation of electrolyte and water balance by increasing the renal retention of sodium and the excretion of potassium. [NIH] Alertness: A state of readiness to detect and respond to certain specified small changes occurring at random intervals in the environment. [NIH] Algorithms: A procedure consisting of a sequence of algebraic formulas and/or logical steps to calculate or determine a given task. [NIH] Alimentary: Pertaining to food or nutritive material, or to the organs of digestion. [EU]
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Alkaline: Having the reactions of an alkali. [EU] Alkaline Phosphatase: An enzyme that catalyzes the conversion of an orthophosphoric monoester and water to an alcohol and orthophosphate. EC 3.1.3.1. [NIH] 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] Alkylating Agents: Highly reactive chemicals that introduce alkyl radicals into biologically active molecules and thereby prevent their proper functioning. Many are used as antineoplastic agents, but most are very toxic, with carcinogenic, mutagenic, teratogenic, and immunosuppressant actions. They have also been used as components in poison gases. [NIH]
Allantois: An embryonic diverticulum of the hindgut of reptiles, birds, and mammals; in man its blood vessels give rise to those of the umbilical cord. [NIH] Alleles: Mutually exclusive forms of the same gene, occupying the same locus on homologous chromosomes, and governing the same biochemical and developmental process. [NIH] Allergen: An antigenic substance capable of producing immediate-type hypersensitivity (allergy). [EU] Allergic Rhinitis: Inflammation of the nasal mucous membrane associated with hay fever; fits may be provoked by substances in the working environment. [NIH] Allogeneic: Taken from different individuals of the same species. [NIH] Allograft: An organ or tissue transplant between two humans. [NIH] Allylamine: Possesses an unusual and selective cytotoxicity for vascular smooth muscle cells in dogs and rats. Useful for experiments dealing with arterial injury, myocardial fibrosis or cardiac decompensation. [NIH] Alopecia: Absence of hair from areas where it is normally present. [NIH] Alpha Particles: Positively charged particles composed of two protons and two neutrons, i.e., helium nuclei, emitted during disintegration of very heavy isotopes; a beam of alpha particles or an alpha ray has very strong ionizing power, but weak penetrability. [NIH] Alpha-1: A protein with the property of inactivating proteolytic enzymes such as leucocyte collagenase and elastase. [NIH] Alpha-Defensins: Defensins found in azurophilic granules of neutrophils and in the secretory granules of intestinal paneth cells. [NIH] Alpha-fetoprotein: AFP. A protein normally produced by a developing fetus. AFP levels are usually undetectable in the blood of healthy nonpregnant adults. An elevated level of AFP suggests the presence of either a primary liver cancer or germ cell tumor. [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] Alveolar Process: The thickest and spongiest part of the maxilla and mandible hollowed out into deep cavities for the teeth. [NIH] Alveoli: Tiny air sacs at the end of the bronchioles in the lungs. [NIH] Ameliorating: A changeable condition which prevents the consequence of a failure or accident from becoming as bad as it otherwise would. [NIH]
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Amenorrhea: Absence of menstruation. [NIH] Amine: An organic compound containing nitrogen; any member of a group of chemical compounds formed from ammonia by replacement of one or more of the hydrogen atoms by organic (hydrocarbon) radicals. The amines are distinguished as primary, secondary, and tertiary, according to whether one, two, or three hydrogen atoms are replaced. The amines include allylamine, amylamine, ethylamine, methylamine, phenylamine, propylamine, and many other compounds. [EU] Amino acid: Any organic compound containing an amino (-NH2 and a carboxyl (- COOH) group. The 20 a-amino acids listed in the accompanying table are the amino acids from which proteins are synthesized by formation of peptide bonds during ribosomal translation of messenger RNA; all except glycine, which is not optically active, have the L configuration. Other amino acids occurring in proteins, such as hydroxyproline in collagen, are formed by posttranslational enzymatic modification of amino acids residues in polypeptide chains. There are also several important amino acids, such as the neurotransmitter y-aminobutyric acid, that have no relation to proteins. Abbreviated AA. [EU] Amino Acid Sequence: The order of amino acids as they occur in a polypeptide chain. This is referred to as the primary structure of proteins. It is of fundamental importance in determining protein conformation. [NIH] Amino-terminal: The end of a protein or polypeptide chain that contains a free amino group (-NH2). [NIH] Ammonia: A colorless alkaline gas. It is formed in the body during decomposition of organic materials during a large number of metabolically important reactions. [NIH] Amnion: The extraembryonic membrane which contains the embryo and amniotic fluid. [NIH]
Amniotic Fluid: Amniotic cavity fluid which is produced by the amnion and fetal lungs and kidneys. [NIH] Amoxicillin: A broad-spectrum semisynthetic antibiotic similar to ampicillin except that its resistance to gastric acid permits higher serum levels with oral administration. [NIH] Amphetamine: A powerful central nervous system stimulant and sympathomimetic. Amphetamine has multiple mechanisms of action including blocking uptake of adrenergics and dopamine, stimulation of release of monamines, and inhibiting monoamine oxidase. Amphetamine is also a drug of abuse and a psychotomimetic. The l- and the d,l-forms are included here. The l-form has less central nervous system activity but stronger cardiovascular effects. The d-form is dextroamphetamine. [NIH] 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]
Amyloidosis: A group of diseases in which protein is deposited in specific organs (localized amyloidosis) or throughout the body (systemic amyloidosis). Amyloidosis may be either primary (with no known cause) or secondary (caused by another disease, including some types of cancer). Generally, primary amyloidosis affects the nerves, skin, tongue, joints, heart, and liver; secondary amyloidosis often affects the spleen, kidneys, liver, and adrenal glands. [NIH]
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Anabolic: Relating to, characterized by, or promoting anabolism. [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] Anaplastic: A term used to describe cancer cells that divide rapidly and bear little or no resemblance to normal cells. [NIH] Anaplastic large cell lymphoma: A rare agressive form of lymphoma (cancer that begins in cells of the lymphatic system) that is usually of T-cell origin. [NIH] Anatomical: Pertaining to anatomy, or to the structure of the organism. [EU] Anchorage: In dentistry, points of retention of fillings and artificial restorations and appliances. [NIH] Androgen-Binding Protein: Carrier proteins produced in the Sertoli cells of the testis, secreted into the seminiferous tubules, and transported via the efferent ducts to the epididymis. They participate in the transport of androgens. Androgen-binding protein has the same amino acid sequence as sex hormone binding-globulin. They differ by their sites of synthesis and post-translational oligosacaccharide modifications. [NIH] Androgens: A class of sex hormones associated with the development and maintenance of the secondary male sex characteristics, sperm induction, and sexual differentiation. In addition to increasing virility and libido, they also increase nitrogen and water retention and stimulate skeletal growth. [NIH] Anemia: A reduction in the number of circulating erythrocytes or in the quantity of hemoglobin. [NIH] Anesthesia: A state characterized by loss of feeling or sensation. This depression of nerve function is usually the result of pharmacologic action and is induced to allow performance of surgery or other painful procedures. [NIH] Anesthetics: Agents that are capable of inducing a total or partial loss of sensation, especially tactile sensation and pain. They may act to induce general anesthesia, in which an unconscious state is achieved, or may act locally to induce numbness or lack of sensation at a targeted site. [NIH] 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] Angiogenesis inhibitor: A substance that may prevent the formation of blood vessels. In anticancer therapy, an angiogenesis inhibitor prevents the growth of blood vessels from surrounding tissue to a solid tumor. [NIH]
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Angioplasty: Endovascular reconstruction of an artery, which may include the removal of atheromatous plaque and/or the endothelial lining as well as simple dilatation. These are procedures performed by catheterization. When reconstruction of an artery is performed surgically, it is called endarterectomy. [NIH] Angiotensinogen: An alpha-globulin of which a fragment of 14 amino acids is converted by renin to angiotensin I, the inactive precursor of angiotensin II. It is a member of the serpin superfamily. [NIH] Animal model: An animal with a disease either the same as or like a disease in humans. Animal models are used to study the development and progression of diseases and to test new treatments before they are given to humans. Animals with transplanted human cancers or other tissues are called xenograft models. [NIH] Anions: Negatively charged atoms, radicals or groups of atoms which travel to the anode or positive pole during electrolysis. [NIH] Ankyrin Repeat: Protein motif that contains a 33-amino acid long sequence that often occurs in tandem arrays. This repeating sequence of 33-amino acids was discovered in ankyrin where it is involved in interaction with the anion exchanger (band 3 protein). Ankyrin repeats cooperatively fold into structures that mediate molecular recognition via proteinprotein interactions. [NIH] Anomalies: Birth defects; abnormalities. [NIH] Anorexia: Lack or loss of appetite for food. Appetite is psychologic, dependent on memory and associations. Anorexia can be brought about by unattractive food, surroundings, or company. [NIH] Anovulation: Suspension or cessation of ovulation in animals and humans. [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] Anterior chamber: The space in front of the iris and behind the cornea. [NIH] Anthracycline: A member of a family of anticancer drugs that are also antibiotics. [NIH] Anti-Anxiety Agents: Agents that alleviate anxiety, tension, and neurotic symptoms, promote sedation, and have a calming effect without affecting clarity of consciousness or neurologic conditions. Some are also effective as anticonvulsants, muscle relaxants, or anesthesia adjuvants. Adrenergic beta-antagonists are commonly used in the symptomatic treatment of anxiety but are not included here. [NIH] Antiarrhythmic: An agent that prevents or alleviates cardiac arrhythmia. [EU] Antibacterial: A substance that destroys bacteria or suppresses their growth or reproduction. [EU] Antibiotic: A drug used to treat infections caused by bacteria and other microorganisms. [NIH]
Antibiotic Prophylaxis: Use of antibiotics before, during, or after a diagnostic, therapeutic, or surgical procedure to prevent infectious complications. [NIH] Antibodies: Immunoglobulin molecules having a specific amino acid sequence by virtue of which they interact only with the antigen that induced their synthesis in cells of the lymphoid series (especially plasma cells), or with an antigen closely related to it. [NIH] Antibody: A type of protein made by certain white blood cells in response to a foreign substance (antigen). Each antibody can bind to only a specific antigen. The purpose of this binding is to help destroy the antigen. Antibodies can work in several ways, depending on
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the nature of the antigen. Some antibodies destroy antigens directly. Others make it easier for white blood cells to destroy the antigen. [NIH] Antibody therapy: Treatment with an antibody, a substance that can directly kill specific tumor cells or stimulate the immune system to kill tumor cells. [NIH] Anticholinergic: An agent that blocks the parasympathetic nerves. Called also parasympatholytic. [EU] Anticoagulant: A drug that helps prevent blood clots from forming. Also called a blood thinner. [NIH] Anticonvulsant: An agent that prevents or relieves convulsions. [EU] Antidepressant: A drug used to treat depression. [NIH] Antidote: A remedy for counteracting a poison. [EU] Antiemetic: An agent that prevents or alleviates nausea and vomiting. Also antinauseant. [EU]
Antifungal: Destructive to fungi, or suppressing their reproduction or growth; effective against fungal infections. [EU] Antigen: Any substance which is capable, under appropriate conditions, of inducing a specific immune response and of reacting with the products of that response, that is, with specific antibody or specifically sensitized T-lymphocytes, or both. Antigens may be soluble substances, such as toxins and foreign proteins, or particulate, such as bacteria and tissue cells; however, only the portion of the protein or polysaccharide molecule known as the antigenic determinant (q.v.) combines with antibody or a specific receptor on a lymphocyte. Abbreviated Ag. [EU] Antigen-Antibody Complex: The complex formed by the binding of antigen and antibody 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] Antihistamine: A drug that counteracts the action of histamine. The antihistamines are of two types. The conventional ones, as those used in allergies, block the H1 histamine receptors, whereas the others block the H2 receptors. Called also antihistaminic. [EU] Antihypertensive: An agent that reduces high blood pressure. [EU] Anti-infective: An agent that so acts. [EU] Anti-inflammatory: Having to do with reducing inflammation. [NIH] Anti-Inflammatory Agents: Substances that reduce or suppress inflammation. [NIH] Antimetabolite: A chemical that is very similar to one required in a normal biochemical reaction in cells. Antimetabolites can stop or slow down the reaction. [NIH] Antimicrobial: Killing microorganisms, or suppressing their multiplication or growth. [EU] Antineoplastic: Inhibiting or preventing the development of neoplasms, checking the maturation and proliferation of malignant cells. [EU] Antineoplastic Agents: Substances that inhibit or prevent the proliferation of neoplasms. [NIH]
Antioxidant: A substance that prevents damage caused by free radicals. Free radicals are highly reactive chemicals that often contain oxygen. They are produced when molecules are split to give products that have unpaired electrons. This process is called oxidation. [NIH] Antiproliferative: Counteracting a process of proliferation. [EU]
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Antipruritic: Relieving or preventing itching. [EU] Antipyretic: An agent that relieves or reduces fever. Called also antifebrile, antithermic and febrifuge. [EU] Antiseptic: A substance that inhibits the growth and development of microorganisms without necessarily killing them. [EU] Antispasmodic: An agent that relieves spasm. [EU] Antitussive: An agent that relieves or prevents cough. [EU] Antiviral: Destroying viruses or suppressing their replication. [EU] Anus: The opening of the rectum to the outside of the body. [NIH] Anxiety: Persistent feeling of dread, apprehension, and impending disaster. [NIH] Anxiety Disorders: Disorders in which anxiety (persistent feelings of apprehension, tension, or uneasiness) is the predominant disturbance. [NIH] Anxiolytic: An anxiolytic or antianxiety agent. [EU] Aorta: The main trunk of the systemic arteries. [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] Applicability: A list of the commodities to which the candidate method can be applied as presented or with minor modifications. [NIH] Aqueous: Having to do with water. [NIH] Aqueous humor: Clear, watery fluid that flows between and nourishes the lens and the cornea; secreted by the ciliary processes. [NIH] Arachidonic Acid: An unsaturated, essential fatty acid. It is found in animal and human fat as well as in the liver, brain, and glandular organs, and is a constituent of animal phosphatides. It is formed by the synthesis from dietary linoleic acid and is a precursor in the biosynthesis of prostaglandins, thromboxanes, and leukotrienes. [NIH] Arginine: An essential amino acid that is physiologically active in the L-form. [NIH] Aromatic: Having a spicy odour. [EU] Arrhythmia: Any variation from the normal rhythm or rate of the heart beat. [NIH] Arsenic trioxide: An anticancer drug that induces programmed cell death (apoptosis) in certain cancer cells. [NIH] Arterial: Pertaining to an artery or to the arteries. [EU] Arteries: The vessels carrying blood away from the heart. [NIH] Arteriolar: Pertaining to or resembling arterioles. [EU] Arterioles: The smallest divisions of the arteries located between the muscular arteries and the capillaries. [NIH] Artery: Vessel-carrying blood from the heart to various parts of the body. [NIH]
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Arthralgia: Pain in the joint. [NIH] Articular: Of or pertaining to a joint. [EU] Ascorbic Acid: A six carbon compound related to glucose. It is found naturally in citrus fruits and many vegetables. Ascorbic acid is an essential nutrient in human diets, and necessary to maintain connective tissue and bone. Its biologically active form, vitamin C, functions as a reducing agent and coenzyme in several metabolic pathways. Vitamin C is considered an antioxidant. [NIH] Aseptic: Free from infection or septic material; sterile. [EU] Asparaginase: A hydrolase enzyme that converts L-asparagine and water to L-aspartate and NH3. EC 3.5.1.1. [NIH] Aspartate: A synthetic amino acid. [NIH] Aspirate: Fluid withdrawn from a lump, often a cyst, or a nipple. [NIH] Assay: Determination of the amount of a particular constituent of a mixture, or of the biological or pharmacological potency of a drug. [EU] Astrocytes: The largest and most numerous neuroglial cells in the brain and spinal cord. Astrocytes (from "star" cells) are irregularly shaped with many long processes, including those with "end feet" which form the glial (limiting) membrane and directly and indirectly contribute to the blood brain barrier. They regulate the extracellular ionic and chemical environment, and "reactive astrocytes" (along with microglia) respond to injury. Astrocytes have high- affinity transmitter uptake systems, voltage-dependent and transmitter-gated ion channels, and can release transmitter, but their role in signaling (as in many other functions) is not well understood. [NIH] Asymptomatic: Having no signs or symptoms of disease. [NIH] Ataxia: Impairment of the ability to perform smoothly coordinated voluntary movements. This condition may affect the limbs, trunk, eyes, pharnyx, larnyx, and other structures. Ataxia may result from impaired sensory or motor function. Sensory ataxia may result from posterior column injury or peripheral nerve diseases. Motor ataxia may be associated with cerebellar diseases; cerebral cortex diseases; thalamic diseases; basal ganglia diseases; injury to the red nucleus; and other conditions. [NIH] Atherectomy: Endovascular procedure in which atheromatous plaque is excised by a cutting or rotating catheter. It differs from balloon and laser angioplasty procedures which enlarge vessels by dilation but frequently do not remove much plaque. If the plaque is removed by surgical excision under general anesthesia rather than by an endovascular procedure through a catheter, it is called endarterectomy. [NIH] ATP: ATP an abbreviation for adenosine triphosphate, a compound which serves as a carrier of energy for cells. [NIH] Atresia: Lack of a normal opening from the esophagus, intestines, or anus. [NIH] Atrial: Pertaining to an atrium. [EU] 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] Atropine: A toxic alkaloid, originally from Atropa belladonna, but found in other plants,
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mainly Solanaceae. [NIH] Attenuation: Reduction of transmitted sound energy or its electrical equivalent. [NIH] Atypical: Irregular; not conformable to the type; in microbiology, applied specifically to strains of unusual type. [EU] Auditory: Pertaining to the sense of hearing. [EU] Aurothioglucose: (1-Thio-D-glucopyranosato)gold. A thioglucose derivative used as an antirheumatic and experimentally to produce obesity in animals. [NIH] Autacoids: A chemically diverse group of substances produced by various tissues in the body that cause slow contraction of smooth muscle; they have other intense but varied pharmacologic activities. [NIH] Autoimmune disease: A condition in which the body recognizes its own tissues as foreign and directs an immune response against them. [NIH] Autoimmunity: Process whereby the immune system reacts against the body's own tissues. Autoimmunity may produce or be caused by autoimmune diseases. [NIH] Autologous: Taken from an individual's own tissues, cells, or DNA. [NIH] Autonomic: Self-controlling; functionally independent. [EU] Autonomic Nervous System: The enteric, parasympathetic, and sympathetic nervous systems taken together. Generally speaking, the autonomic nervous system regulates the internal environment during both peaceful activity and physical or emotional stress. Autonomic activity is controlled and integrated by the central nervous system, especially the hypothalamus and the solitary nucleus, which receive information relayed from visceral afferents; these and related central and sensory structures are sometimes (but not here) considered to be part of the autonomic nervous system itself. [NIH] Avian: A plasmodial infection in birds. [NIH] Axons: Nerve fibers that are capable of rapidly conducting impulses away from the neuron cell body. [NIH] Bacteria: Unicellular prokaryotic microorganisms which generally possess rigid cell walls, multiply by cell division, and exhibit three principal forms: round or coccal, rodlike or bacillary, and spiral or spirochetal. [NIH] Bacterial Infections: Infections by bacteria, general or unspecified. [NIH] Bactericidal: Substance lethal to bacteria; substance capable of killing bacteria. [NIH] 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] Balloon dilation: A treatment for benign prostatic hyperplasia or prostate enlargement. A tiny balloon is inflated inside the urethra to make it wider so urine can flow more freely from the bladder. [NIH] Band 3 Protein: A ubiquitous membrane transport protein found in the plasma membrane of diverse cell types and tissues, and in nuclear, mitochondrial, and Golgi membranes. It is the major integral transmembrane protein of the erythrocyte membrane, comprising 25% of
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the total membrane protein and occurring at 1 million copies per cell. It exists as a dimer and provides a channel for the transport of anions across the membrane. [NIH] Barbiturate: A drug with sedative and hypnotic effects. Barbiturates have been used as sedatives and anesthetics, and they have been used to treat the convulsions associated with epilepsy. [NIH] Basal Ganglia: Large subcortical nuclear masses derived from the telencephalon and located in the basal regions of the cerebral hemispheres. [NIH] Basal Ganglia Diseases: Diseases of the basal ganglia including the putamen; globus pallidus; claustrum; amygdala; and caudate nucleus. Dyskinesias (most notably involuntary movements and alterations of the rate of movement) represent the primary clinical manifestations of these disorders. Common etiologies include cerebrovascular disease; neurodegenerative diseases; and craniocerebral trauma. [NIH] Base: In chemistry, the nonacid part of a salt; a substance that combines with acids to form salts; a substance that dissociates to give hydroxide ions in aqueous solutions; a substance whose molecule or ion can combine with a proton (hydrogen ion); a substance capable of donating a pair of electrons (to an acid) for the formation of a coordinate covalent bond. [EU] 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] Beclomethasone: An anti-inflammatory, synthetic glucocorticoid. It is used topically as an anti-inflammatory agent and in aerosol form for the treatment of asthma. [NIH] Benign: Not cancerous; does not invade nearby tissue or spread to other parts of the body. [NIH]
Benign prostatic hyperplasia: A benign (noncancerous) condition in which an overgrowth of prostate tissue pushes against the urethra and the bladder, blocking the flow of urine. Also called benign prostatic hypertrophy or BPH. [NIH] Benzyl Alcohol: A colorless liquid with a sharp burning taste and slight odor. It is used as a local anesthetic and to reduce pain associated with lidocaine injection. Also, it is used in the manufacture of other benzyl compounds, as a pharmaceutic aid, and in perfumery and flavoring. [NIH] Beta-Defensins: Defensins found mainly in epithelial cells. [NIH] Beta-Endorphin: A peptide consisting of amino acid sequence 61-91 of the endogenous pituitary hormone beta-lipotropin. The first four amino acids show a common tetrapeptide sequence with methionine- and leucine enkephalin. The compound shows opiate-like activity. Injection of beta-endorphin induces a profound analgesia of the whole body for several hours. This action is reversed after administration of naloxone. [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] Betaxolol: A cardioselective beta-1-adrenergic antagonist with no partial agonist activity. [NIH]
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Bilateral: Affecting both the right and left side of body. [NIH] Bile: An emulsifying agent produced in the liver and secreted into the duodenum. Its composition includes bile acids and salts, cholesterol, and electrolytes. It aids digestion of fats in the duodenum. [NIH] Bile Acids: Acids made by the liver that work with bile to break down fats. [NIH] Bile Acids and Salts: Steroid acids and salts. The primary bile acids are derived from cholesterol in the liver and usually conjugated with glycine or taurine. The secondary bile acids are further modified by bacteria in the intestine. They play an important role in the digestion and absorption of fat. They have also been used pharmacologically, especially in the treatment of gallstones. [NIH] Bile duct: A tube through which bile passes in and out of the liver. [NIH] Biliary: Having to do with the liver, bile ducts, and/or gallbladder. [NIH] Biliary Tract: The gallbladder and its ducts. [NIH] Bilirubin: A bile pigment that is a degradation product of heme. [NIH] Binding Sites: The reactive parts of a macromolecule that directly participate in its specific combination with another molecule. [NIH] Bioartificial Organs: Artificial organs that are composites of biomaterials and cells. The biomaterial can act as a membrane (container) as in bioartificial liver or a scaffold as in bioartificial skin. [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] Bioavailable: The ability of a drug or other substance to be absorbed and used by the body. Orally bioavailable means that a drug or other substance that is taken by mouth can be absorbed and used by the body. [NIH] Biochemical: Relating to biochemistry; characterized by, produced by, or involving chemical reactions in living organisms. [EU] Biochemical reactions: In living cells, chemical reactions that help sustain life and allow cells to grow. [NIH] Biogenic Amines: A group of naturally occurring amines derived by enzymatic decarboxylation of the natural amino acids. Many have powerful physiological effects (e.g., histamine, serotonin, epinephrine, tyramine). Those derived from aromatic amino acids, and also their synthetic analogs (e.g., amphetamine), are of use in pharmacology. [NIH] Biological 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] 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
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protein structure function analysis and prediction. [NIH] Biotin: Hexahydro-2-oxo-1H-thieno(3,4-d)imidazole-4-pentanoic acid. Growth factor present in minute amounts in every living cell. It occurs mainly bound to proteins or polypeptides and is abundant in liver, kidney, pancreas, yeast, and milk.The biotin content of cancerous tissue is higher than that of normal tissue. [NIH] Bipolar Disorder: A major affective disorder marked by severe mood swings (manic or major depressive episodes) and a tendency to remission and recurrence. [NIH] Bivalent: Pertaining to a group of 2 homologous or partly homologous chromosomes during the zygotene stage of prophase to the first metaphase in meiosis. [NIH] Bladder: The organ that stores urine. [NIH] Blastocyst: The mammalian embryo in the post-morula stage in which a fluid-filled cavity, enclosed primarily by trophoblast, contains an inner cell mass which becomes the embryonic disc. [NIH] 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] Blister: Visible accumulations of fluid within or beneath the epidermis. [NIH] Blood Coagulation: The process of the interaction of blood coagulation factors that results in an insoluble fibrin clot. [NIH] Blood Coagulation Factors: Endogenous substances, usually proteins, that are involved in the blood coagulation process. [NIH] Blood Glucose: Glucose in blood. [NIH] Blood Platelets: Non-nucleated disk-shaped cells formed in the megakaryocyte and found in the blood of all mammals. They are mainly involved in blood coagulation. [NIH] Blood pressure: The pressure of blood against the walls of a blood vessel or heart chamber. Unless there is reference to another location, such as the pulmonary artery or one of the heart chambers, it refers to the pressure in the systemic arteries, as measured, for example, in the forearm. [NIH] Blood Proteins: Proteins that are present in blood serum, including serum albumin, blood coagulation factors, and many other types of proteins. [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 correlation with skinfold thickness or body density. [NIH] Bolus: A single dose of drug usually injected into a blood vessel over a short period of time. Also called bolus infusion. [NIH] Bolus infusion: A single dose of drug usually injected into a blood vessel over a short
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period of time. Also called bolus. [NIH] Bolus injection: The injection of a drug (or drugs) in a high quantity (called a bolus) at once, the opposite of gradual administration (as in intravenous infusion). [EU] 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 metastases: Cancer that has spread from the original (primary) tumor to the bone. [NIH]
Bone scan: A technique to create images of bones on a computer screen or on film. A small amount of radioactive material is injected into a blood vessel and travels through the bloodstream; it collects in the bones and is detected by a scanner. [NIH] Boron: A trace element with the atomic symbol B, atomic number 5, and atomic weight 10.81. Boron-10, an isotope of boron, is used as a neutron absorber in boron neutron capture therapy. [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] Breast Neoplasms: Tumors or cancer of the breast. [NIH] Breast reconstruction: Surgery to rebuild a breast's shape after a mastectomy. [NIH] Breeding: The science or art of changing the constitution of a population of plants or animals through sexual reproduction. [NIH] Broad-spectrum: Effective against a wide range of microorganisms; said of an antibiotic. [EU] Bronchi: The larger air passages of the lungs arising from the terminal bifurcation of the trachea. [NIH] Bronchial: Pertaining to one or more bronchi. [EU]
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Bronchitis: Inflammation (swelling and reddening) of the bronchi. [NIH] Bronchoconstriction: Diminution of the caliber of a bronchus physiologically or as a result of pharmacological intervention. [NIH] Bronchodilator: A drug that relaxes the smooth muscles in the constricted airway. [NIH] Bronchopulmonary: Pertaining to the lungs and their air passages; both bronchial and pulmonary. [EU] Bronchopulmonary Dysplasia: A chronic lung disease appearing in certain newborn infants treated for respiratory distress syndrome with mechanical ventilation and elevated concentration of inspired oxygen. [NIH] Bronchospasm: Spasmodic contraction of the smooth muscle of the bronchi, as occurs in asthma. [EU] Bronchus: A large air passage that leads from the trachea (windpipe) to the lung. [NIH] Brown Fat: A thermogenic form of adipose tissue found in newborns of many species, including humans, and in hibernating mammals. The tissue is capable of rapid liberation of energy and seems to be important in the maintenance of body temperature immediately after birth and upon waking from hibernation. [NIH] Buccal: Pertaining to or directed toward the cheek. In dental anatomy, used to refer to the buccal surface of a tooth. [EU] Budesonide: A glucocorticoid used in the management of asthma, the treatment of various skin disorders, and allergic rhinitis. [NIH] Bullous: Pertaining to or characterized by bullae. [EU] Bumetanide: A sulfamyl diuretic. [NIH] Bupivacaine: A widely used local anesthetic agent. [NIH] Buprenorphine: A derivative of the opioid alkaloid thebaine that is a more potent and longer lasting analgesic than morphine. It appears to act as a partial agonist at mu and kappa opioid receptors and as an antagonist at delta receptors. The lack of delta-agonist activity has been suggested to account for the observation that buprenorphine tolerance may not develop with chronic use. [NIH] Burns: Injuries to tissues caused by contact with heat, steam, chemicals (burns, chemical), electricity (burns, electric), or the like. [NIH] Buserelin: A potent and durable analog of naturally occurring gonadotropin-releasing hormone (GnRH). [NIH] Bypass: A surgical procedure in which the doctor creates a new pathway for the flow of body fluids. [NIH] Cachexia: General ill health, malnutrition, and weight loss, usually associated with chronic disease. [NIH] Cadmium: An element with atomic symbol Cd, atomic number 48, and atomic weight 114. It is a metal and ingestion will lead to cadmium poisoning. [NIH] Cadmium Poisoning: Poisoning occurring after exposure to cadmium compounds or fumes. It may cause gastrointestinal syndromes, anemia, or pneumonitis. [NIH] Caffeine: A methylxanthine naturally occurring in some beverages and also used as a pharmacological agent. Caffeine's most notable pharmacological effect is as a central nervous system stimulant, increasing alertness and producing agitation. It also relaxes smooth muscle, stimulates cardiac muscle, stimulates diuresis, and appears to be useful in the treatment of some types of headache. Several cellular actions of caffeine have been
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observed, but it is not entirely clear how each contributes to its pharmacological profile. Among the most important are inhibition of cyclic nucleotide phosphodiesterases, antagonism of adenosine receptors, and modulation of intracellular calcium handling. [NIH] Calcifediol: The major circulating metabolite of vitamin D3 produced in the liver and the best indicator of the body's vitamin D stores. It is effective in the treatment of rickets and osteomalacia, both in azotemic and non-azotemic patients. Calcifediol also has mineralizing properties. [NIH] Calcitriol: The physiologically active form of vitamin D. It is formed primarily in the kidney by enzymatic hydroxylation of 25-hydroxycholecalciferol (calcifediol). Its production is stimulated by low blood calcium levels and parathyroid hormone. Calcitriol increases intestinal absorption of calcium and phosphorus, and in concert with parathyroid hormone increases bone resorption. [NIH] Calcium: A basic element found in nearly all organized tissues. It is a member of the alkaline earth family of metals with the atomic symbol Ca, atomic number 20, and atomic weight 40. Calcium is the most abundant mineral in the body and combines with phosphorus to form calcium phosphate in the bones and teeth. It is essential for the normal functioning of nerves and muscles and plays a role in blood coagulation (as factor IV) and in many enzymatic processes. [NIH] Calcium channel blocker: A drug used to relax the blood vessel and heart muscle, causing pressure inside blood vessels to drop. It also can regulate heart rhythm. [NIH] Calcium Channels: Voltage-dependent cell membrane glycoproteins selectively permeable to calcium ions. They are categorized as L-, T-, N-, P-, Q-, and R-types based on the activation and inactivation kinetics, ion specificity, and sensitivity to drugs and toxins. The L- and T-types are present throughout the cardiovascular and central nervous systems and the N-, P-, Q-, & R-types are located in neuronal tissue. [NIH] Calibration: Determination, by measurement or comparison with a standard, of the correct value of each scale reading on a meter or other measuring instrument; or determination of the settings of a control device that correspond to particular values of voltage, current, frequency, or other output. [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] Camphor: A bicyclic monoterpene ketone found widely in plant (primarily the camphor tree, Cinnamomum camphora). Natural camphor is used topically as a skin antipruritic and as an anti-infective agent. [NIH] Camptothecin: An alkaloid isolated from the stem wood of the Chinese tree, Camptotheca acuminata. This compound selectively inhibits the nuclear enzyme DNA topoisomerase. Several semisynthetic analogs of camptothecin have demonstrated antitumor activity. [NIH] 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]
Cannabidiol: Compound isolated from Cannabis sativa extract. [NIH] Cannabinoids: Compounds extracted from Cannabis sativa L. and metabolites having the
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cannabinoid structure. The most active constituents are tetrahydrocannabinol, cannabinol, and cannabidiol. [NIH] Cannabinol: A physiologically inactive constituent of Cannabis sativa L. [NIH] Cannula: A tube for insertion into a duct or cavity; during insertion its lumen is usually occupied by a trocar. [EU] Capsaicin: Cytotoxic alkaloid from various species of Capsicum (pepper, paprika), of the Solanaceae. [NIH] Carbamazepine: An anticonvulsant used to control grand mal and psychomotor or focal seizures. Its mode of action is not fully understood, but some of its actions resemble those of phenytoin; although there is little chemical resemblance between the two compounds, their three-dimensional structure is similar. [NIH] Carbenoxolone: An agent derived from licorice root. It is used for the treatment of digestive tract ulcers, especially in the stomach. Antidiuretic side effects are frequent, but otherwise the drug is low in toxicity. [NIH] Carbohydrate: An aldehyde or ketone derivative of a polyhydric alcohol, particularly of the pentahydric and hexahydric alcohols. They are so named because the hydrogen and oxygen are usually in the proportion to form water, (CH2O)n. The most important carbohydrates are the starches, sugars, celluloses, and gums. They are classified into mono-, di-, tri-, polyand heterosaccharides. [EU] Carbon Dioxide: A colorless, odorless gas that can be formed by the body and is necessary for the respiration cycle of plants and animals. [NIH] Carboplatin: An organoplatinum compound that possesses antineoplastic activity. [NIH] Carcinogen: Any substance that causes cancer. [NIH] Carcinogenesis: The process by which normal cells are transformed into cancer cells. [NIH] Carcinogenic: Producing carcinoma. [EU] Carcinoma: Cancer that begins in the skin or in tissues that line or cover internal organs. [NIH]
Cardiac: Having to do with the heart. [NIH] Cardiomyopathy: A general diagnostic term designating primary myocardial disease, often of obscure or unknown etiology. [EU] Cardiopulmonary: Having to do with the heart and lungs. [NIH] Cardiopulmonary Bypass: Diversion of the flow of blood from the entrance of the right atrium directly to the aorta (or femoral artery) via an oxygenator thus bypassing both the heart and lungs. [NIH] Cardioselective: Having greater activity on heart tissue than on other tissue. [EU] Cardiotoxicity: Toxicity that affects the heart. [NIH] Cardiovascular: Having to do with the heart and blood vessels. [NIH] Cardiovascular disease: Any abnormal condition characterized by dysfunction of the heart and blood vessels. CVD includes atherosclerosis (especially coronary heart disease, which can lead to heart attacks), cerebrovascular disease (e.g., stroke), and hypertension (high blood pressure). [NIH] Carmustine: An anticancer drug that belongs to the family of drugs called alkylating agents. [NIH]
Carotid Arteries: Either of the two principal arteries on both sides of the neck that supply blood to the head and neck; each divides into two branches, the internal carotid artery and
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the external carotid artery. [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] Catabolism: Any destructive metabolic process by which organisms convert substances into excreted compounds. [EU] Cataract: An opacity, partial or complete, of one or both eyes, on or in the lens or capsule, especially an opacity impairing vision or causing blindness. The many kinds of cataract are classified by their morphology (size, shape, location) or etiology (cause and time of occurrence). [EU] Catecholamine: A group of chemical substances manufactured by the adrenal medulla and secreted during physiological stress. [NIH] Catheter: A flexible tube used to deliver fluids into or withdraw fluids from the body. [NIH] Catheterization: Use or insertion of a tubular device into a duct, blood vessel, hollow organ, or body cavity for injecting or withdrawing fluids for diagnostic or therapeutic purposes. It differs from intubation in that the tube here is used to restore or maintain patency in obstructions. [NIH] 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] 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] Celecoxib: A drug that reduces pain. Celecoxib belongs to the family of drugs called nonsteroidal anti-inflammatory agents. It is being studied for cancer prevention. [NIH] Cell: The individual unit that makes up all of the tissues of the body. All living things are made up of one or more cells. [NIH] Cell Adhesion: Adherence of cells to surfaces or to other cells. [NIH] Cell Adhesion Molecules: Surface ligands, usually glycoproteins, that mediate cell-to-cell adhesion. Their functions include the assembly and interconnection of various vertebrate systems, as well as maintenance of tissue integration, wound healing, morphogenic movements, cellular migrations, and metastasis. [NIH] Cell Aggregation: The phenomenon by which dissociated cells intermixed in vitro tend to group themselves with cells of their own type. [NIH] Cell Death: The termination of the cell's ability to carry out vital functions such as metabolism, growth, reproduction, responsiveness, and adaptability. [NIH] Cell Differentiation: Progressive restriction of the developmental potential and increasing specialization of function which takes place during the development of the embryo and leads to the formation of specialized cells, tissues, and organs. [NIH] Cell Division: The fission of a cell. [NIH] Cell Lineage: The developmental history of cells as traced from the first division of the original cell or cells in the embryo. [NIH]
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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 Polarity: Orientation of intracellular structures especially with respect to the apical and basolateral domains of the plasma membrane. Polarized cells must direct proteins from the Golgi apparatus to the appropriate domain since tight junctions prevent proteins from diffusing between the two domains. [NIH] Cell proliferation: An increase in the number of cells as a result of cell growth and cell division. [NIH] Cell Size: The physical dimensions of a cell. It refers mainly to changes in dimensions correlated with physiological or pathological changes in cells. [NIH] Cell Survival: The span of viability of a cell characterized by the capacity to perform certain functions such as metabolism, growth, reproduction, some form of responsiveness, and adaptability. [NIH] Cell Transplantation: Transference of cells within an individual, between individuals of the same species, or between individuals of different species. [NIH] Cellular adhesion: The close adherence (bonding) to adjoining cell surfaces. [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] Cerebellar: Pertaining to the cerebellum. [EU] Cerebral: Of or pertaining of the cerebrum or the brain. [EU] Cerebral Cortex: The thin layer of gray matter on the surface of the cerebral hemisphere that develops from the telencephalon and folds into gyri. It reaches its highest development in man and is responsible for intellectual faculties and higher mental functions. [NIH] Cerebral hemispheres: The two halves of the cerebrum, the part of the brain that controls muscle functions of the body and also controls speech, emotions, reading, writing, and learning. The right hemisphere controls muscle movement on the left side of the body, and the left hemisphere controls muscle movement on the right side of the body. [NIH] Cerebral Palsy: Refers to a motor disability caused by a brain dysfunction. [NIH] 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]
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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] Cesarean Section: Extraction of the fetus by means of abdominal hysterotomy. [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] Chemoprevention: The use of drugs, vitamins, or other agents to try to reduce the risk of, or delay the development or recurrence of, cancer. [NIH] Chemopreventive: Natural or synthetic compound used to intervene in the early precancerous stages of carcinogenesis. [NIH] Chemotactic Factors: Chemical substances that attract or repel cells or organisms. The concept denotes especially those factors released as a result of tissue injury, invasion, or immunologic activity, that attract leukocytes, macrophages, or other cells to the site of infection or insult. [NIH] Chemotaxis: The movement of cells or organisms toward or away from a substance in response to its concentration gradient. [NIH] Chemotherapeutic agent: A drug used to treat cancer. [NIH] Chemotherapy: Treatment with anticancer drugs. [NIH] Chest wall: The ribs and muscles, bones, and joints that make up the area of the body between the neck and the abdomen. [NIH] Chickenpox: A mild, highly contagious virus characterized by itchy blisters all over the body. [NIH] Chimeras: Organism that contains a mixture of genetically different cells. [NIH] Chin: The anatomical frontal portion of the mandible, also known as the mentum, that contains the line of fusion of the two separate halves of the mandible (symphysis menti). This line of fusion divides inferiorly to enclose a triangular area called the mental protuberance. On each side, inferior to the second premolar tooth, is the mental foramen for the passage of blood vessels and a nerve. [NIH] Chlorobutanol: A colorless to white crystalline compound with a camphoraceous odor and taste. It is a widely used preservative in various pharmaceutical solutions, especially injectables. Also, it is an active ingredient in certain oral sedatives and topical anesthetics. [NIH]
Chlorophyll: Porphyrin derivatives containing magnesium that act to convert light energy in photosynthetic organisms. [NIH] Cholecystectomy: Surgical removal of the gallbladder. [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] Cholinergic: Resembling acetylcholine in pharmacological action; stimulated by or releasing acetylcholine or a related compound. [EU]
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Chondrocytes: Polymorphic cells that form cartilage. [NIH] Chondrosarcoma: A type of cancer that forms in cartilage. [NIH] Chorion: The outermost extraembryonic membrane. [NIH] Chromaffin System: The cells of the body which stain with chromium salts. They occur along the sympathetic nerves, in the adrenal gland, and in various other organs. [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] Chromium: A trace element that plays a role in glucose metabolism. It has the atomic symbol Cr, atomic number 24, and atomic weight 52. According to the Fourth Annual Report on Carcinogens (NTP85-002,1985), chromium and some of its compounds have been listed as known carcinogens. [NIH] Chromosomal: Pertaining to chromosomes. [EU] Chromosome: Part of a cell that contains genetic information. Except for sperm and eggs, all human cells contain 46 chromosomes. [NIH] Chronic: A disease or condition that persists or progresses over a long period of time. [NIH] Chronic Disease: Disease or ailment of long duration. [NIH] Chronic Fatigue Syndrome: Fatigue caused by the combined effects of different types of prolonged fatigue. [NIH] Chronic lymphocytic leukemia: A slowly progressing disease in which too many white blood cells (called lymphocytes) are found in the body. [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 Body: A ring of tissue extending from the scleral spur to the ora serrata of the retina. It consists of the uveal portion and the epithelial portion. The ciliary muscle is in the uveal portion and the ciliary processes are in the epithelial portion. [NIH] Ciliary processes: The extensions or projections of the ciliary body that secrete aqueous humor. [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] Circulatory system: The system that contains the heart and the blood vessels and moves blood throughout the body. This system helps tissues get enough oxygen and nutrients, and it helps them get rid of waste products. The lymph system, which connects with the blood system, is often considered part of the circulatory system. [NIH] CIS: Cancer Information Service. The CIS is the National Cancer Institute's link to the public, interpreting and explaining research findings in a clear and understandable manner, and providing personalized responses to specific questions about cancer. Access the CIS by calling 1-800-4-CANCER, or by using the Web site at http://cis.nci.nih.gov. [NIH] Cisplatin: An inorganic and water-soluble platinum complex. After undergoing hydrolysis, it reacts with DNA to produce both intra and interstrand crosslinks. These crosslinks appear to impair replication and transcription of DNA. The cytotoxicity of cisplatin correlates with
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cellular arrest in the G2 phase of the cell cycle. [NIH] Citalopram: A selective neuronal serotonin reuptake inhibitor and a clinically effective antidepressant with tolerable side effects. The drug is also effective in reducing ethanol uptake in alcoholics and is used in depressed patients who also suffer from tardive dyskinesia (TD) in preference to tricyclic antidepressants, which aggravate this condition. [NIH]
Citrus: Any tree or shrub of the Rue family or the fruit of these plants. [NIH] Clamp: A u-shaped steel rod used with a pin or wire for skeletal traction in the treatment of certain fractures. [NIH] Clarithromycin: A semisynthetic macrolide antibiotic derived from erythromycin that is active against a variety of microorganisms. It can inhibit protein synthesis in bacteria by reversibly binding to the 50S ribosomal subunits. This inhibits the translocation of aminoacyl transfer-RNA and prevents peptide chain elongation. [NIH] Clathrin: The main structural coat protein of coated vesicles which play a key role in the intracellular transport between membranous organelles. Clathrin also interacts with cytoskeletal proteins. [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] 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] Clomiphene: A stilbene derivative that functions both as a partial estrogen agonist and complete estrogen antagonist depending on the target tissue. It antagonizes the estrogen receptor thereby initiating or augmenting ovulation in anovulatory women. [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] Cloprostenol: A synthetic prostaglandin F2alpha analog. The compound has luteolytic effects and is used for the synchronization of estrus in cattle. [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] Coated Vesicles: Vesicles formed when cell-membrane coated pits invaginate and pinch off. The outer surface of these vesicles are covered with a lattice-like network of coat proteins, such as clathrin, coat protein complex proteins, or caveolins. [NIH]
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Coca: Any of several South American shrubs of the Erythroxylon genus (and family) that yield cocaine; the leaves are chewed with alum for CNS stimulation. [NIH] Cocaine: An alkaloid ester extracted from the leaves of plants including coca. It is a local anesthetic and vasoconstrictor and is clinically used for that purpose, particularly in the eye, ear, nose, and throat. It also has powerful central nervous system effects similar to the amphetamines and is a drug of abuse. Cocaine, like amphetamines, acts by multiple mechanisms on brain catecholaminergic neurons; the mechanism of its reinforcing effects is thought to involve inhibition of dopamine uptake. [NIH] 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]
Cochlear: Of or pertaining to the cochlea. [EU] Cod Liver Oil: Oil obtained from fresh livers of the cod family, Gadidae. It is a source of vitamins A and D. [NIH] Coenzyme: An organic nonprotein molecule, frequently a phosphorylated derivative of a water-soluble vitamin, that binds with the protein molecule (apoenzyme) to form the active enzyme (holoenzyme). [EU] Cofactor: A substance, microorganism or environmental factor that activates or enhances the action of another entity such as a disease-causing agent. [NIH] Colitis: Inflammation of the colon. [NIH] Collagen: A polypeptide substance comprising about one third of the total protein in mammalian organisms. It is the main constituent of skin, connective tissue, and the organic substance of bones and teeth. Different forms of collagen are produced in the body but all consist of three alpha-polypeptide chains arranged in a triple helix. Collagen is differentiated from other fibrous proteins, such as elastin, by the content of proline, hydroxyproline, and hydroxylysine; by the absence of tryptophan; and particularly by the high content of polar groups which are responsible for its swelling properties. [NIH] Collagen disease: A term previously used to describe chronic diseases of the connective tissue (e.g., rheumatoid arthritis, systemic lupus erythematosus, and systemic sclerosis), but now is thought to be more appropriate for diseases associated with defects in collagen, which is a component of the connective tissue. [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] Colon: The long, coiled, tubelike organ that removes water from digested food. The remaining material, solid waste called stool, moves through the colon to the rectum and leaves the body through the anus. [NIH] Colorectal: Having to do with the colon or the rectum. [NIH] Colorectal Cancer: Cancer that occurs in the colon (large intestine) or the rectum (the end of the large intestine). A number of digestive diseases may increase a person's risk of colorectal cancer, including polyposis and Zollinger-Ellison Syndrome. [NIH] Combination chemotherapy: Treatment using more than one anticancer drug. [NIH] Combination Therapy: Association of 3 drugs to treat AIDS (AZT + DDC or DDI + protease inhibitor). [NIH]
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Comorbidity: The presence of co-existing or additional diseases with reference to an initial diagnosis or with reference to the index condition that is the subject of study. Comorbidity may affect the ability of affected individuals to function and also their survival; it may be used as a prognostic indicator for length of hospital stay, cost factors, and outcome or survival. [NIH] Complement: A term originally used to refer to the heat-labile factor in serum that causes immune cytolysis, the lysis of antibody-coated cells, and now referring to the entire functionally related system comprising at least 20 distinct serum proteins that is the effector not only of immune cytolysis but also of other biologic functions. Complement activation occurs by two different sequences, the classic and alternative pathways. The proteins of the classic pathway are termed 'components of complement' and are designated by the symbols C1 through C9. C1 is a calcium-dependent complex of three distinct proteins C1q, C1r and C1s. The proteins of the alternative pathway (collectively referred to as the properdin system) and complement regulatory proteins are known by semisystematic or trivial names. Fragments resulting from proteolytic cleavage of complement proteins are designated with lower-case letter suffixes, e.g., C3a. Inactivated fragments may be designated with the suffix 'i', e.g. C3bi. Activated components or complexes with biological activity are designated by a bar over the symbol e.g. C1 or C4b,2a. The classic pathway is activated by the binding of C1 to classic pathway activators, primarily antigen-antibody complexes containing IgM, IgG1, IgG3; C1q binds to a single IgM molecule or two adjacent IgG molecules. The alternative pathway can be activated by IgA immune complexes and also by nonimmunologic materials including bacterial endotoxins, microbial polysaccharides, and cell walls. Activation of the classic pathway triggers an enzymatic cascade involving C1, C4, C2 and C3; activation of the alternative pathway triggers a cascade involving C3 and factors B, D and P. Both result in the cleavage of C5 and the formation of the membrane attack complex. Complement activation also results in the formation of many biologically active complement fragments that act as anaphylatoxins, opsonins, or chemotactic factors. [EU] Complement Activation: The sequential activation of serum components C1 through C9, initiated by an erythrocyte-antibody complex or by microbial polysaccharides and properdin, and producing an inflammatory response. [NIH] Complementary and alternative medicine: CAM. Forms of treatment that are used in addition to (complementary) or instead of (alternative) standard treatments. These practices are not considered standard medical approaches. CAM includes dietary supplements, megadose vitamins, herbal preparations, special teas, massage therapy, magnet therapy, spiritual healing, and meditation. [NIH] Complementary medicine: Practices not generally recognized by the medical community as standard or conventional medical approaches and used to enhance or complement the standard treatments. Complementary medicine includes the taking of dietary supplements, megadose vitamins, and herbal preparations; the drinking of special teas; and practices such as massage therapy, magnet therapy, spiritual healing, and meditation. [NIH] Complete remission: The disappearance of all signs of cancer. Also called a complete response. [NIH] Complete response: The disappearance of all signs of cancer in response to treatment. This does not always mean the cancer has been cured. [NIH] Compliance: Distensibility measure of a chamber such as the lungs (lung compliance) or bladder. Compliance is expressed as a change in volume per unit change in pressure. [NIH] Computational Biology: A field of biology concerned with the development of techniques for the collection and manipulation of biological data, and the use of such data to make biological discoveries or predictions. This field encompasses all computational methods and
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theories applicable to molecular biology and areas of computer-based techniques for solving biological problems including manipulation of models and datasets. [NIH] Concentration Camps: Facilities in which war or political prisoners are confined. [NIH] Conception: The onset of pregnancy, marked by implantation of the blastocyst; the formation of a viable zygote. [EU] Concomitant: Accompanying; accessory; joined with another. [EU] Conduction: The transfer of sound waves, heat, nervous impulses, or electricity. [EU] Congestion: Excessive or abnormal accumulation of blood in a part. [EU] Conjugated: Acting or operating as if joined; simultaneous. [EU] Conjugation: 1. The act of joining together or the state of being conjugated. 2. A sexual process seen in bacteria, ciliate protozoa, and certain fungi in which nuclear material is exchanged during the temporary fusion of two cells (conjugants). In bacterial genetics a form of sexual reproduction in which a donor bacterium (male) contributes some, or all, of its DNA (in the form of a replicated set) to a recipient (female) which then incorporates differing genetic information into its own chromosome by recombination and passes the recombined set on to its progeny by replication. In ciliate protozoa, two conjugants of separate mating types exchange micronuclear material and then separate, each now being a fertilized cell. In certain fungi, the process involves fusion of two gametes, resulting in union of their nuclei and formation of a zygote. 3. In chemistry, the joining together of two compounds to produce another compound, such as the combination of a toxic product with some substance in the body to form a detoxified product, which is then eliminated. [EU] 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] Constipation: Infrequent or difficult evacuation of feces. [NIH] Constitutional: 1. Affecting the whole constitution of the body; not local. 2. Pertaining to the constitution. [EU] Constriction: The act of constricting. [NIH] Consumption: Pulmonary tuberculosis. [NIH] Contamination: The soiling or pollution by inferior material, as by the introduction of organisms into a wound, or sewage into a stream. [EU] Continuous infusion: The administration of a fluid into a blood vessel, usually over a prolonged period of time. [NIH] 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]
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Control group: In a clinical trial, the group that does not receive the new treatment being studied. This group is compared to the group that receives the new treatment, to see if the new treatment works. [NIH] Controlled study: An experiment or clinical trial that includes a comparison (control) group. [NIH]
Cooperative group: A group of physicians, hospitals, or both formed to treat a large number of persons in the same way so that new treatment can be evaluated quickly. Clinical trials of new cancer treatments often require many more people than a single physician or hospital can care for. [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] Corn Oil: Oil from corn or corn plant. [NIH] Cornea: The transparent part of the eye that covers the iris and the pupil and allows light to enter the inside. [NIH] Corneal Transplantation: Partial or total replacement of the cornea from one human or animal to another. [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 Artery Bypass: Surgical therapy of ischemic coronary artery disease achieved by grafting a section of saphenous vein, internal mammary artery, or other substitute between the aorta and the obstructed coronary artery distal to the obstructive lesion. [NIH] Coronary heart disease: A type of heart disease caused by narrowing of the coronary arteries that feed the heart, which needs a constant supply of oxygen and nutrients carried by the blood in the coronary arteries. When the coronary arteries become narrowed or clogged by fat and cholesterol deposits and cannot supply enough blood to the heart, CHD results. [NIH] Coronary Thrombosis: Presence of a thrombus in a coronary artery, often causing a myocardial infarction. [NIH] 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]
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Cortical: Pertaining to or of the nature of a cortex or bark. [EU] Corticosteroid: Any of the steroids elaborated by the adrenal cortex (excluding the sex hormones of adrenal origin) in response to the release of corticotrophin (adrenocorticotropic hormone) by the pituitary gland, to any of the synthetic equivalents of these steroids, or to angiotensin II. They are divided, according to their predominant biological activity, into three major groups: glucocorticoids, chiefly influencing carbohydrate, fat, and protein metabolism; mineralocorticoids, affecting the regulation of electrolyte and water balance; and C19 androgens. Some corticosteroids exhibit both types of activity in varying degrees, and others exert only one type of effect. The corticosteroids are used clinically for hormonal replacement therapy, for suppression of ACTH secretion by the anterior pituitary, as antineoplastic, antiallergic, and anti-inflammatory agents, and to suppress the immune response. Called also adrenocortical hormone and corticoid. [EU] Corticotropin-Releasing Hormone: A neuropeptide released by the hypothalamus that stimulates the release of corticotropin by the anterior pituitary gland. [NIH] Cortisol: A steroid hormone secreted by the adrenal cortex as part of the body's response to stress. [NIH] Cortisone: A natural steroid hormone produced in the adrenal gland. It can also be made in the laboratory. Cortisone reduces swelling and can suppress immune responses. [NIH] Cost-benefit: A quantitative technique of economic analysis which, when applied to radiation practice, compares the health detriment from the radiation doses concerned with the cost of radiation dose reduction in that practice. [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] Criterion: A standard by which something may be judged. [EU] Croup: A condition characterized by resonant barking cough, hoarseness and persistant stridor and caused by allergy, foreign body, infection, or neoplasm. It occurs chiefly in infants and children. [NIH] Cryptococcosis: Infection with a fungus of the species Cryptococcus neoformans. [NIH] Cryptosporidiosis: Parasitic intestinal infection with severe diarrhea caused by a protozoan, Cryptosporidium. It occurs in both animals and humans. [NIH] Culture Media: Any liquid or solid preparation made specifically for the growth, storage, or transport of microorganisms or other types of cells. The variety of media that exist allow for the culturing of specific microorganisms and cell types, such as differential media, selective media, test media, and defined media. Solid media consist of liquid media that have been solidified with an agent such as agar or gelatin. [NIH] Cultured cells: Animal or human cells that are grown in the laboratory. [NIH] Curative: Tending to overcome disease and promote recovery. [EU] Curcumin: A dye obtained from tumeric, the powdered root of Curcuma longa Linn. It is used in the preparation of curcuma paper and the detection of boron. Curcumin appears to possess a spectrum of pharmacological properties, due primarily to its inhibitory effects on metabolic enzymes. [NIH] Cutaneous: Having to do with the skin. [NIH]
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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] Cyclodextrins: A homologous group of cyclic glucans consisting of alpha-1,4 bound glucose units obtained by the action of cyclodextrin glucanotransferase on starch or similar substrates. The enzyme is produced by certain species of Bacillus. Cyclodextrins form inclusion complexes with a wide variety of substances. [NIH] Cyclophosphamide: Precursor of an alkylating nitrogen mustard antineoplastic and immunosuppressive agent that must be activated in the liver to form the active aldophosphamide. It is used in the treatment of lymphomas, leukemias, etc. Its side effect, alopecia, has been made use of in defleecing sheep. Cyclophosphamide may also cause sterility, birth defects, mutations, and cancer. [NIH] Cyclosporine: A drug used to help reduce the risk of rejection of organ and bone marrow transplants by the body. It is also used in clinical trials to make cancer cells more sensitive to anticancer drugs. [NIH] Cyclosporins: A group of closely related cyclic undecapeptides from the fungi Trichoderma polysporum and Cylindocarpon lucidum. They have some antineoplastic and antifungal action and significant immunosuppressive effects. Cyclosporins have been proposed as adjuvants in tissue and organ transplantation to suppress graft rejection. [NIH] Cyst: A sac or capsule filled with fluid. [NIH] Cysteinyl: Enzyme released by the cell at a crucial stage in apoptosis in order to shred all cellular proteins. [NIH] Cytarabine: An anticancer drug that belongs to the family of drugs called antimetabolites. [NIH]
Cytochrome: Any electron transfer hemoprotein having a mode of action in which the transfer of a single electron is effected by a reversible valence change of the central iron atom of the heme prosthetic group between the +2 and +3 oxidation states; classified as cytochromes a in which the heme contains a formyl side chain, cytochromes b, which contain protoheme or a closely similar heme that is not covalently bound to the protein, cytochromes c in which protoheme or other heme is covalently bound to the protein, and cytochromes d in which the iron-tetrapyrrole has fewer conjugated double bonds than the hemes have. Well-known cytochromes have been numbered consecutively within groups and are designated by subscripts (beginning with no subscript), e.g. cytochromes c, c1, C2, . New cytochromes are named according to the wavelength in nanometres of the absorption maximum of the a-band of the iron (II) form in pyridine, e.g., c-555. [EU] Cytogenetics: A branch of genetics which deals with the cytological and molecular behavior of genes and chromosomes during cell division. [NIH] Cytokine: Small but highly potent protein that modulates the activity of many cell types, including T and B cells. [NIH] Cytomegalovirus: A genus of the family Herpesviridae, subfamily Betaherpesvirinae, infecting the salivary glands, liver, spleen, lungs, eyes, and other organs, in which they produce characteristically enlarged cells with intranuclear inclusions. Infection with Cytomegalovirus is also seen as an opportunistic infection in AIDS. [NIH] Cytoplasm: The protoplasm of a cell exclusive of that of the nucleus; it consists of a continuous aqueous solution (cytosol) and the organelles and inclusions suspended in it (phaneroplasm), and is the site of most of the chemical activities of the cell. [EU] Cytoskeleton: The network of filaments, tubules, and interconnecting filamentous bridges
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which give shape, structure, and organization to the cytoplasm. [NIH] Cytostatic: An agent that suppresses cell growth and multiplication. [EU] Cytotoxic: Cell-killing. [NIH] Cytotoxic chemotherapy: Anticancer drugs that kill cells, especially cancer cells. [NIH] Cytotoxicity: Quality of being capable of producing a specific toxic action upon cells of special organs. [NIH] Daunorubicin: Very toxic anthracycline aminoglycoside antibiotic isolated from Streptomyces peucetius and others, used in treatment of leukemias and other neoplasms. [NIH]
Deamination: The removal of an amino group (NH2) from a chemical compound. [NIH] Decarboxylation: The removal of a carboxyl group, usually in the form of carbon dioxide, from a chemical compound. [NIH] Decidua: The epithelial lining of the endometrium that is formed before the fertilized ovum reaches the uterus. The fertilized ovum embeds in the decidua. If the ovum is not fertilized, the decidua is shed during menstruation. [NIH] Decompression: Decompression external to the body, most often the slow lessening of external pressure on the whole body (especially in caisson workers, deep sea divers, and persons who ascend to great heights) to prevent decompression sickness. It includes also sudden accidental decompression, but not surgical (local) decompression or decompression applied through body openings. [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] Defensins: Family of antimicrobial peptides that have been identified in humans, animals, and plants. They are thought to play a role in host defenses against infections, inflammation, wound repair, and acquired immunity. Based on the disulfide pairing of their characteristic six cysteine residues, they are divided into alpha-defensins and beta-defensins. [NIH] Degenerative: Undergoing degeneration : tending to degenerate; having the character of or involving degeneration; causing or tending to cause degeneration. [EU] Dehydroepiandrosterone: DHEA. A substance that is being studied as a cancer prevention drug. It belongs to the family of drugs called steroids. [NIH] Deletion: A genetic rearrangement through loss of segments of DNA (chromosomes), bringing sequences, which are normally separated, into close proximity. [NIH] Dementia: An acquired organic mental disorder with loss of intellectual abilities of sufficient severity to interfere with social or occupational functioning. The dysfunction is multifaceted and involves memory, behavior, personality, judgment, attention, spatial relations, language, abstract thought, and other executive functions. The intellectual decline is usually progressive, and initially spares the level of consciousness. [NIH] Dendrites: Extensions of the nerve cell body. They are short and branched and receive stimuli from other neurons. [NIH] 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]
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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] Deprivation: Loss or absence of parts, organs, powers, or things that are needed. [EU] Dermatitis: Any inflammation of the skin. [NIH] Dermis: A layer of vascular connective tissue underneath the epidermis. The surface of the dermis contains sensitive papillae. Embedded in or beneath the dermis are sweat glands, hair follicles, and sebaceous glands. [NIH] Desensitization: The prevention or reduction of immediate hypersensitivity reactions by administration of graded doses of allergen; called also hyposensitization and immunotherapy. [EU] Detoxification: Treatment designed to free an addict from his drug habit. [EU] Deuterium: Deuterium. The stable isotope of hydrogen. It has one neutron and one proton in the nucleus. [NIH] Developed Countries: Countries that have reached a level of economic achievement through an increase of production, per capita income and consumption, and utilization of natural and human resources. [NIH] Developing Countries: Countries in the process of change directed toward economic growth, that is, an increase in production, per capita consumption, and income. The process of economic growth involves better utilization of natural and human resources, which results in a change in the social, political, and economic structures. [NIH] DEXA: A method (dual energy X-ray absortiometry) used to estimate total body fat and percent of body fat. Potential disadvantages include whole body radiation and the long time required for scanning while the subject lies on a hard table. [NIH] Dexamethasone: (11 beta,16 alpha)-9-Fluoro-11,17,21-trihydroxy-16-methylpregna-1,4diene-3,20-dione. An anti-inflammatory glucocorticoid used either in the free alcohol or esterified form in treatment of conditions that respond generally to cortisone. [NIH] Diabetes Mellitus: A heterogeneous group of disorders that share glucose intolerance in common. [NIH] Diagnostic procedure: A method used to identify a disease. [NIH] Diaphragm: The musculofibrous partition that separates the thoracic cavity from the abdominal cavity. Contraction of the diaphragm increases the volume of the thoracic cavity aiding inspiration. [NIH] Diarrhea: Passage of excessively liquid or excessively frequent stools. [NIH] Diarrhoea: Abnormal frequency and liquidity of faecal discharges. [EU] Diastolic: Of or pertaining to the diastole. [EU] Diclofenac: A non-steroidal anti-inflammatory agent (NSAID) with antipyretic and analgesic actions. It is primarily available as the sodium salt, diclofenac sodium. [NIH] Diclofenac Sodium: The sodium form of diclofenac. It is used for its analgesic and antiinflammatory properties. [NIH] Diencephalon: The paired caudal parts of the prosencephalon from which the thalamus, hypothalamus, epithalamus, and subthalamus are derived. [NIH]
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Diethylstilbestrol: DES. 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] Digestion: The process of breakdown of food for metabolism and use by the body. [NIH] Digestive system: The organs that take in food and turn it into products that the body can use to stay healthy. Waste products the body cannot use leave the body through bowel movements. The digestive system includes the salivary glands, mouth, esophagus, stomach, liver, pancreas, gallbladder, small and large intestines, and rectum. [NIH] Digestive tract: The organs through which food passes when food is eaten. These organs are the mouth, esophagus, stomach, small and large intestines, and rectum. [NIH] Dihydrotestosterone: Anabolic agent. [NIH] Dilatation: The act of dilating. [NIH] Dilation: A process by which the pupil is temporarily enlarged with special eye drops (mydriatic); allows the eye care specialist to better view the inside of the eye. [NIH] Dimethyl: A volatile metabolite of the amino acid methionine. [NIH] Dimethyl Sulfoxide: A highly polar organic liquid, that is used widely as a chemical solvent. Because of its ability to penetrate biological membranes, it is used as a vehicle for topical application of pharmaceuticals. It is also used to protect tissue during cryopreservation. Dimethyl sulfoxide shows a range of pharmacological activity including analgesia and anti-inflammation. [NIH] Diphenhydramine: A histamine H1 antagonist used as an antiemetic, antitussive, for dermatoses and pruritus, for hypersensitivity reactions, as a hypnotic, an antiparkinson, and as an ingredient in common cold preparations. It has some undesired antimuscarinic and sedative effects. [NIH] Direct: 1. Straight; in a straight line. 2. Performed immediately and without the intervention of subsidiary means. [EU] Disease Progression: The worsening of a disease over time. This concept is most often used for chronic and incurable diseases where the stage of the disease is an important determinant of therapy and prognosis. [NIH] Disinfectant: An agent that disinfects; applied particularly to agents used on inanimate objects. [EU] Disposition: A tendency either physical or mental toward certain diseases. [EU] Dissection: Cutting up of an organism for study. [NIH] Dissociation: 1. The act of separating or state of being separated. 2. The separation of a molecule into two or more fragments (atoms, molecules, ions, or free radicals) produced by the absorption of light or thermal energy or by solvation. 3. In psychology, a defense mechanism in which a group of mental processes are segregated from the rest of a person's mental activity in order to avoid emotional distress, as in the dissociative disorders (q.v.), or in which an idea or object is segregated from its emotional significance; in the first sense it is roughly equivalent to splitting, in the second, to isolation. 4. A defect of mental integration in which one or more groups of mental processes become separated off from normal consciousness and, thus separated, function as a unitary whole. [EU] Dissociative Disorders: Sudden temporary alterations in the normally integrative functions of consciousness. [NIH] Distal: Remote; farther from any point of reference; opposed to proximal. In dentistry, used
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to designate a position on the dental arch farther from the median line of the jaw. [EU] Diuresis: Increased excretion of urine. [EU] Diurnal: Occurring during the day. [EU] Dizziness: An imprecise term which may refer to a sense of spatial disorientation, motion of the environment, or lightheadedness. [NIH] DNA Topoisomerase: An enzyme catalyzing ATP-independent breakage of single-stranded DNA, followed by passage and rejoining of another single-stranded DNA. This enzyme class brings about the conversion of one topological isomer of DNA into another, e.g., the relaxation of superhelical turns in DNA, the interconversion of simple and knotted rings of single-stranded DNA, and the intertwisting of single-stranded rings of complementary sequences. (From Enzyme Nomenclature, 1992) EC 5.99.1.2. [NIH] Docetaxel: An anticancer drug that belongs to the family of drugs called mitotic inhibitors. [NIH]
Domesticated: Species in which the evolutionary process has been influenced by humans to meet their needs. [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] Dose-limiting: Describes side effects of a drug or other treatment that are serious enough to prevent an increase in dose or level of that treatment. [NIH] Double-blind: Pertaining to a clinical trial or other experiment in which neither the subject nor the person administering treatment knows which treatment any particular subject is receiving. [EU] 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] Doxorubicin: Antineoplastic antibiotic obtained from Streptomyces peucetics. It is a hydroxy derivative of daunorubicin and is used in treatment of both leukemia and solid tumors. [NIH] Drinking Behavior: Behaviors associated with the ingesting of water and other liquids; includes rhythmic patterns of drinking (time intervals - onset and duration), frequency and satiety. [NIH] Drive: A state of internal activity of an organism that is a necessary condition before a given stimulus will elicit a class of responses; e.g., a certain level of hunger (drive) must be present before food will elicit an eating response. [NIH] Drug Combinations: Single preparations containing two or more active agents, for the purpose of their concurrent administration as a fixed dose mixture. It is differentiated from combination drug therapy in which two or more drugs are administered separately for a combined effect. [NIH] Drug Delivery Systems: Systems of administering drugs through controlled delivery so that an optimum amount reaches the target site. Drug delivery systems encompass the carrier,
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route, and target. [NIH] Drug Interactions: The action of a drug that may affect the activity, metabolism, or toxicity of another drug. [NIH] Drug Resistance: Diminished or failed response of an organism, disease or tissue to the intended effectiveness of a chemical or drug. It should be differentiated from drug tolerance which is the progressive diminution of the susceptibility of a human or animal to the effects of a drug, as a result of continued administration. [NIH] Drug Tolerance: Progressive diminution of the susceptibility of a human or animal to the effects of a drug, resulting from its continued administration. It should be differentiated from drug resistance wherein an organism, disease, or tissue fails to respond to the intended effectiveness of a chemical or drug. It should also be differentiated from maximum tolerated dose and no-observed-adverse-effect level. [NIH] Duct: A tube through which body fluids pass. [NIH] Duodenum: The first part of the small intestine. [NIH] Dura mater: The outermost, toughest, and most fibrous of the three membranes (meninges) covering the brain and spinal cord; called also pachymeninx. [EU] Dyskinesia: Impairment of the power of voluntary movement, resulting in fragmentary or incomplete movements. [EU] Dysmenorrhea: Painful menstruation. [NIH] Dysplasia: Cells that look abnormal under a microscope but are not cancer. [NIH] Dystocia: Difficult childbirth or labor. [NIH] Dystrophy: Any disorder arising from defective or faulty nutrition, especially the muscular dystrophies. [EU] Echothiophate Iodide: A potent, long-acting cholinesterase inhibitor used as a miotic in the treatment of glaucoma. [NIH] Ectopic: Pertaining to or characterized by ectopia. [EU] Eczema: A pruritic papulovesicular dermatitis occurring as a reaction to many endogenous and exogenous agents (Dorland, 27th ed). [NIH] Edema: Excessive amount of watery fluid accumulated in the intercellular spaces, most commonly present in subcutaneous tissue. [NIH] Effector: It is often an enzyme that converts an inactive precursor molecule into an active second messenger. [NIH] Effector cell: A cell that performs a specific function in response to a stimulus; usually used to describe cells in the immune system. [NIH] Efficacy: The extent to which a specific intervention, procedure, regimen, or service produces a beneficial result under ideal conditions. Ideally, the determination of efficacy is based on the results of a randomized control trial. [NIH] Eicosanoids: A class of oxygenated, endogenous, unsaturated fatty acids derived from arachidonic acid. They include prostaglandins, leukotrienes, thromboxanes, and hydroxyeicosatetraenoic acid compounds (HETE). They are hormone-like substances that act near the site of synthesis without altering functions throughout the body. [NIH] Ejection fraction: A measure of ventricular contractility, equal to normally 65 8 per cent; lower values indicate ventricular dysfunction. [EU] Elastic: Susceptible of resisting and recovering from stretching, compression or distortion applied by a force. [EU]
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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] Electrode: Component of the pacing system which is at the distal end of the lead. It is the interface with living cardiac tissue across which the stimulus is transmitted. [NIH] Electroencephalography: Recording of electric currents developed in the brain by means of electrodes applied to the scalp, to the surface of the brain, or placed within the substance of the brain. [NIH] Electrolyte: A substance that dissociates into ions when fused or in solution, and thus becomes capable of conducting electricity; an ionic solute. [EU] Elementary Particles: Individual components of atoms, usually subatomic; subnuclear particles are usually detected only when the atomic nucleus decays and then only transiently, as most of them are unstable, often yielding pure energy without substance, i.e., radiation. [NIH] Emaciation: Clinical manifestation of excessive leanness usually caused by disease or a lack of nutrition. [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] Embolus: Bit of foreign matter which enters the blood stream at one point and is carried until it is lodged or impacted in an artery and obstructs it. It may be a blood clot, an air bubble, fat or other tissue, or clumps of bacteria. [NIH] Embryo: The prenatal stage of mammalian development characterized by rapid morphological changes and the differentiation of basic structures. [NIH] Embryogenesis: The process of embryo or embryoid formation, whether by sexual (zygotic) or asexual means. In asexual embryogenesis embryoids arise directly from the explant or on intermediary callus tissue. In some cases they arise from individual cells (somatic cell embryoge). [NIH] Embryology: The study of the development of an organism during the embryonic and fetal stages of life. [NIH] Emesis: Vomiting; an act of vomiting. Also used as a word termination, as in haematemesis. [EU]
Emetic: An agent that causes vomiting. [EU] Emollient: Softening or soothing; called also malactic. [EU] Emphysema: A pathological accumulation of air in tissues or organs. [NIH] Emulsion: A preparation of one liquid distributed in small globules throughout the body of a second liquid. The dispersed liquid is the discontinuous phase, and the dispersion medium is the continuous phase. When oil is the dispersed liquid and an aqueous solution is the continuous phase, it is known as an oil-in-water emulsion, whereas when water or aqueous solution is the dispersed phase and oil or oleaginous substance is the continuous phase, it is known as a water-in-oil emulsion. Pharmaceutical emulsions for which official standards have been promulgated include cod liver oil emulsion, cod liver oil emulsion with malt, liquid petrolatum emulsion, and phenolphthalein in liquid petrolatum emulsion. [EU] Encapsulated: Confined to a specific, localized area and surrounded by a thin layer of tissue.
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[NIH]
Endarterectomy: Surgical excision, performed under general anesthesia, of the atheromatous tunica intima of an artery. When reconstruction of an artery is performed as an endovascular procedure through a catheter, it is called atherectomy. [NIH] Endocarditis: Exudative and proliferative inflammatory alterations of the endocardium, characterized by the presence of vegetations on the surface of the endocardium or in the endocardium itself, and most commonly involving a heart valve, but sometimes affecting the inner lining of the cardiac chambers or the endocardium elsewhere. It may occur as a primary disorder or as a complication of or in association with another disease. [EU] Endocrine Glands: Ductless glands that secrete substances which are released directly into the circulation and which influence metabolism and other body functions. [NIH] Endocrine System: The system of glands that release their secretions (hormones) directly into the circulatory system. In addition to the endocrine glands, included are the chromaffin system and the neurosecretory systems. [NIH] Endogenous: Produced inside an organism or cell. The opposite is external (exogenous) production. [NIH] Endolymphatic Duct: Duct connecting the endolymphatic sac with the membranous labyrinth. [NIH] Endolymphatic Sac: The blind pouch at the end of the endolymphatic duct. [NIH] Endometrium: The layer of tissue that lines the uterus. [NIH] Endophthalmitis: Suppurative inflammation of the tissues of the internal structures of the eye; not all layers of the uvea are affected. Fungi, necrosis of intraocular tumors, and retained intraocular foreign bodies often cause a purulent endophthalmitis. [NIH] Endorphins: One of the three major groups of endogenous opioid peptides. They are large peptides derived from the pro-opiomelanocortin precursor. The known members of this group are alpha-, beta-, and gamma-endorphin. The term endorphin is also sometimes used to refer to all opioid peptides, but the narrower sense is used here; opioid peptides is used for the broader group. [NIH] 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] Endosomes: Cytoplasmic vesicles formed when coated vesicles shed their clathrin coat. Endosomes internalize macromolecules bound by receptors on the cell surface. [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] Energy balance: Energy is the capacity of a body or a physical system for doing work. Energy balance is the state in which the total energy intake equals total energy needs. [NIH]
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Enhancer: Transcriptional element in the virus genome. [NIH] Enkephalin: A natural opiate painkiller, in the hypothalamus. [NIH] Enterocytes: Terminally differentiated cells comprising the majority of the external surface of the intestinal epithelium (see intestinal mucosa). Unlike goblet cells, they do not produce or secrete mucins, nor do they secrete cryptdins as do the paneth cells. [NIH] 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] Eosinophil: A polymorphonuclear leucocyte with large eosinophilic granules in its cytoplasm, which plays a role in hypersensitivity reactions. [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] Epicondylitis: Inflammation of the epicondyle or of the tissues adjoining the epicondyle of the humerus. [EU] Epidermal: Pertaining to or resembling epidermis. Called also epidermic or epidermoid. [EU] Epidermal Growth Factor: A 6 kD polypeptide growth factor initially discovered in mouse submaxillary glands. Human epidermal growth factor was originally isolated from urine based on its ability to inhibit gastric secretion and called urogastrone. epidermal growth factor exerts a wide variety of biological effects including the promotion of proliferation and differentiation of mesenchymal and epithelial cells. [NIH] Epidermis: Nonvascular layer of the skin. It is made up, from within outward, of five layers: 1) basal layer (stratum basale epidermidis); 2) spinous layer (stratum spinosum epidermidis); 3) granular layer (stratum granulosum epidermidis); 4) clear layer (stratum lucidum epidermidis); and 5) horny layer (stratum corneum epidermidis). [NIH] Epidermoid carcinoma: A type of cancer in which the cells are flat and look like fish scales. Also called squamous cell carcinoma. [NIH] Epidural: The space between the wall of the spinal canal and the covering of the spinal cord. An epidural injection is given into this space. [NIH] 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] Epirubicin: An anthracycline antibiotic which is the 4'-epi-isomer of doxorubicin. The compound exerts its antitumor effects by interference with the synthesis and function of DNA. Clinical studies indicate activity in breast cancer, non-Hodgkin's lymphomas, ovarian cancer, soft-tissue sarcomas, pancreatic cancer, gastric cancer, small-cell lung cancer and acute leukemia. It is equal in activity to doxorubicin but exhibits less acute toxicities and less
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cardiotoxicity. [NIH] Epithelial: Refers to the cells that line the internal and external surfaces of the body. [NIH] Epithelial Cells: Cells that line the inner and outer surfaces of the body. [NIH] Epithelium: One or more layers of epithelial cells, supported by the basal lamina, which covers the inner or outer surfaces of the body. [NIH] Epitope: A molecule or portion of a molecule capable of binding to the combining site of an antibody. For every given antigenic determinant, the body can construct a variety of antibody-combining sites, some of which fit almost perfectly, and others which barely fit. [NIH]
Epoetin alfa: A colony-stimulating factor that is made in the laboratory. It increases the production of red blood cells. [NIH] Epoxide Hydrolases: Enzymes that catalyze reversibly the formation of an epoxide or arene oxide from a glycol or aromatic diol, respectively. EC 3.3.2.3. [NIH] Erythema: Redness of the skin produced by congestion of the capillaries. This condition may result from a variety of causes. [NIH] Erythema Nodosum: An erythematous eruption commonly associated with drug reactions or infection and characterized by inflammatory nodules that are usually tender, multiple, and bilateral. These nodules are located predominantly on the shins with less common occurrence on the thighs and forearms. They undergo characteristic color changes ending in temporary bruise-like areas. This condition usually subsides in 3-6 weeks without scarring or atrophy. [NIH] Erythroblasts: Immature, nucleated erythrocytes occupying the stage of erythropoiesis that follows formation of erythroid progenitor cells and precedes formation of reticulocytes. Popularly called normoblasts. [NIH] Erythrocyte Volume: Volume of circulating erythrocytes. It is usually measured by radioisotope dilution technique. [NIH] Erythrocytes: Red blood cells. Mature erythrocytes are non-nucleated, biconcave disks containing hemoglobin whose function is to transport oxygen. [NIH] Erythroid Progenitor Cells: Committed, erythroid stem cells derived from myeloid stem cells. The progenitor cells develop in two phases: erythroid burst-forming units (BFU-E) followed by erythroid colony-forming units (CFU-E). BFU-E differentiate into CFU-E on stimulation by erythropoietin, and then further differentiate into erythroblasts when stimulated by other factors. [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] 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 passes from the throat to the stomach. [NIH] Esophagus: The muscular tube through which food passes from the throat to the stomach. [NIH]
Esotropia: A form of ocular misalignment characterized by an excessive convergence of the visual axes, resulting in a "cross-eye" appearance. An example of this condition occurs when
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paralysis of the lateral rectus muscle causes an abnormal inward deviation of one eye on attempted gaze. [NIH] Essential Tremor: A rhythmic, involuntary, purposeless, oscillating movement resulting from the alternate contraction and relaxation of opposing groups of muscles. [NIH] Estradiol: The most potent mammalian estrogenic hormone. It is produced in the ovary, placenta, testis, and possibly the adrenal cortex. [NIH] Estrogen: One of the two female sex hormones. [NIH] Estrogen receptor: ER. Protein found on some cancer cells to which estrogen will attach. [NIH]
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] Etoposide: A semisynthetic derivative of podophyllotoxin that exhibits antitumor activity. Etoposide inhibits DNA synthesis by forming a complex with topoisomerase II and DNA. This complex induces breaks in double stranded DNA and prevents repair by topoisomerase II binding. Accumulated breaks in DNA prevent entry into the mitotic phase of cell division, and lead to cell death. Etoposide acts primarily in the G2 and S phases of the cell cycle. [NIH] Eukaryotic Cells: Cells of the higher organisms, containing a true nucleus bounded by a nuclear membrane. [NIH] Eustachian tube: The middle ear cavity is in communication with the back of the nose through the Eustachian tube, which is normally closed, but opens on swallowing, in order to maintain equal air pressure. [NIH] Evacuation: An emptying, as of the bowels. [EU] Evoke: The electric response recorded from the cerebral cortex after stimulation of a peripheral sense organ. [NIH] 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] Exercise Test: Controlled physical activity, more strenuous than at rest, which is performed in order to allow assessment of physiological functions, particularly cardiovascular and pulmonary, but also aerobic capacity. Maximal (most intense) exercise is usually required but submaximal exercise is also used. The intensity of exercise is often graded, using criteria such as rate of work done, oxygen consumption, and heart rate. Physiological data obtained from an exercise test may be used for diagnosis, prognosis, and evaluation of disease severity, and to evaluate therapy. Data may also be used in prescribing exercise by determining a person's exercise capacity. [NIH] Exocrine: Secreting outwardly, via a duct. [EU] Exogenous: Developed or originating outside the organism, as exogenous disease. [EU] Exotropia: A form of ocular misalignment where the visual axes diverge inappropriately.
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For example, medial rectus muscle weakness may produce this condition as the affected eye will deviate laterally upon attempted forward gaze. An exotropia occurs due to the relatively unopposed force exerted on the eye by the lateral rectus muscle, which pulls the eye in an outward direction. [NIH] 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] Extender: 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. [NIH] External-beam radiation: Radiation therapy that uses a machine to aim high-energy rays at the cancer. Also called external radiation. [NIH] Extracellular: Outside a cell or cells. [EU] Extracellular Matrix: A meshwork-like substance found within the extracellular space and in association with the basement membrane of the cell surface. It promotes cellular proliferation and provides a supporting structure to which cells or cell lysates in culture dishes adhere. [NIH] Extracellular Matrix Proteins: Macromolecular organic compounds that contain carbon, hydrogen, oxygen, nitrogen, and usually, sulfur. These macromolecules (proteins) form an intricate meshwork in which cells are embedded to construct tissues. Variations in the relative types of macromolecules and their organization determine the type of extracellular matrix, each adapted to the functional requirements of the tissue. The two main classes of 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] Extracorporeal: Situated or occurring outside the body. [EU] Extraocular: External to or outside of the eye. [NIH] Extrarenal: Outside of the kidney. [EU] Extravasation: A discharge or escape, as of blood, from a vessel into the tissues. [EU] Extravascular: Situated or occurring outside a vessel or the vessels. [EU] Extremity: A limb; an arm or leg (membrum); sometimes applied specifically to a hand or foot. [EU] Facial: Of or pertaining to the face. [EU] Facial Expression: Observable changes of expression in the face in response to emotional stimuli. [NIH] Family Planning: Programs or services designed to assist the family in controlling reproduction by either improving or diminishing fertility. [NIH] Fat: Total lipids including phospholipids. [NIH] Fatal Outcome: Death resulting from the presence of a disease in an individual, as shown by a single case report or a limited number of patients. This should be differentiated from death, the physiological cessation of life and from mortality, an epidemiological or statistical concept. [NIH] Fatigue: The state of weariness following a period of exertion, mental or physical, characterized by a decreased capacity for work and reduced efficiency to respond to stimuli. [NIH]
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Fatty acids: A major component of fats that are used by the body for energy and tissue development. [NIH] Femoral: Pertaining to the femur, or to the thigh. [EU] Femoral Artery: The main artery of the thigh, a continuation of the external iliac artery. [NIH] Fentanyl: A narcotic opioid drug that is used in the treatment of pain. [NIH] Fetal Blood: Blood of the fetus. Exchange of nutrients and waste between the fetal and maternal blood occurs via the placenta. The cord blood is blood contained in the umbilical vessels at the time of delivery. [NIH] Fetal Heart: The heart of the fetus of any viviparous animal. It refers to the heart in the postembryonic period and is differentiated from the embryonic heart (heart/embryology) only on the basis of time. [NIH] Fetal Membranes: Thin layers of tissue which surround the embryo or fetus and provide for its nutrition, respiration, excretion and protection; they are the yolk sac, allantois, amnion, and chorion. [NIH] Fetoprotein: Transabdominal aspiration of fluid from the amniotic sac with a view to detecting increases of alpha-fetoprotein in maternal blood during pregnancy, as this is an important indicator of open neural tube defects in the fetus. [NIH] Fetus: The developing offspring from 7 to 8 weeks after conception until birth. [NIH] Fibrin: A protein derived from fibrinogen in the presence of thrombin, which forms part of the blood clot. [NIH] Fibrinogen: Plasma glycoprotein clotted by thrombin, composed of a dimer of three nonidentical pairs of polypeptide chains (alpha, beta, gamma) held together by disulfide bonds. Fibrinogen clotting is a sol-gel change involving complex molecular arrangements: whereas fibrinogen is cleaved by thrombin to form polypeptides A and B, the proteolytic action of other enzymes yields different fibrinogen degradation products. [NIH] Fibroblasts: Connective tissue cells which secrete an extracellular matrix rich in collagen and other macromolecules. [NIH] Fibronectins: Glycoproteins found on the surfaces of cells, particularly in fibrillar structures. The proteins are lost or reduced when these cells undergo viral or chemical transformation. They are highly susceptible to proteolysis and are substrates for activated blood coagulation factor VIII. The forms present in plasma are called cold-insoluble globulins. [NIH] Fibrosarcoma: A type of soft tissue sarcoma that begins in fibrous tissue, which holds bones, muscles, and other organs in place. [NIH] Fibrosis: Any pathological condition where fibrous connective tissue invades any organ, usually as a consequence of inflammation or other injury. [NIH] Fistula: Abnormal communication most commonly seen between two internal organs, or between an internal organ and the surface of the body. [NIH] Flatulence: Production or presence of gas in the gastrointestinal tract which may be expelled through the anus. [NIH] Flatus: Gas passed through the rectum. [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
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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] Floxuridine: An antineoplastic antimetabolite that is metabolized to fluorouracil when administered by rapid injection; when administered by slow, continuous, intra-arterial infusion, it is converted to floxuridine monophosphate. It has been used to treat hepatic metastases of gastrointestinal adenocarcinomas and for palliation in malignant neoplasms of the liver and gastrointestinal tract. [NIH] Fludarabine: An anticancer drug that belongs to the family of drugs called antimetabolites. [NIH]
Flumethasone: An anti-inflammatory glucocorticoid used in veterinary practice. [NIH] Fluorescence: The property of emitting radiation while being irradiated. The radiation emitted is usually of longer wavelength than that incident or absorbed, e.g., a substance can be irradiated with invisible radiation and emit visible light. X-ray fluorescence is used in diagnosis. [NIH] Fluorescent Dyes: Dyes that emit light when exposed to light. The wave length of the emitted light is usually longer than that of the incident light. Fluorochromes are substances that cause fluorescence in other substances, i.e., dyes used to mark or label other compounds with fluorescent tags. They are used as markers in biochemistry and immunology. [NIH] Fluorouracil: A pyrimidine analog that acts as an antineoplastic antimetabolite and also has immunosuppressant. It interferes with DNA synthesis by blocking the thymidylate synthetase conversion of deoxyuridylic acid to thymidylic acid. [NIH] Fluoxymesterone: An anabolic steroid that has been used in the treatment of male hypogonadism, delayed puberty in males, and in the treatment of breast neoplasms in women. [NIH] Flushing: A transient reddening of the face that may be due to fever, certain drugs, exertion, stress, or a disease process. [NIH] Foetal: Of or pertaining to a fetus; pertaining to in utero development after the embryonic period. [EU] Folate: A B-complex vitamin that is being studied as a cancer prevention agent. Also called folic acid. [NIH] Fold: A plication or doubling of various parts of the body. [NIH] Folic Acid: N-(4-(((2-Amino-1,4-dihydro-4-oxo-6-pteridinyl)methyl)amino)benzoyl)-Lglutamic acid. A member of the vitamin B family that stimulates the hematopoietic system. It is present in the liver and kidney and is found in mushrooms, spinach, yeast, green leaves, and grasses. Folic acid is used in the treatment and prevention of folate deficiencies and megaloblastic anemia. [NIH] Follicles: Shafts through which hair grows. [NIH] Foramen: A natural hole of perforation, especially one in a bone. [NIH] Forearm: The part between the elbow and the wrist. [NIH] Fossa: A cavity, depression, or pit. [NIH] Free Radicals: Highly reactive molecules with an unsatisfied electron valence pair. Free radicals are produced in both normal and pathological processes. They are proven or suspected agents of tissue damage in a wide variety of circumstances including radiation, damage from environment chemicals, and aging. Natural and pharmacological prevention of free radical damage is being actively investigated. [NIH]
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Functional Disorders: Disorders such as irritable bowel syndrome. These conditions result from poor nerve and muscle function. Symptoms such as gas, pain, constipation, and diarrhea come back again and again, but there are no signs of disease or damage. Emotional stress can trigger symptoms. Also called motility disorders. [NIH] Functional magnetic resonance imaging: A noninvasive tool used to observe functioning in the brain or other organs by detecting changes in chemical composition, blood flow, or both. [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] Fungistatic: Inhibiting the growth of fungi. [EU] Fungus: A general term used to denote a group of eukaryotic protists, including mushrooms, yeasts, rusts, moulds, smuts, etc., which are characterized by the absence of chlorophyll and by the presence of a rigid cell wall composed of chitin, mannans, and sometimes cellulose. They are usually of simple morphological form or show some reversible cellular specialization, such as the formation of pseudoparenchymatous tissue in the fruiting body of a mushroom. The dimorphic fungi grow, according to environmental conditions, as moulds or yeasts. [EU] Gadolinium: An element of the rare earth family of metals. It has the atomic symbol Gd, atomic number 64, and atomic weight 157.25. Its oxide is used in the control rods of some nuclear reactors. [NIH] Gallate: Antioxidant present in tea. [NIH] Gallbladder: The pear-shaped organ that sits below the liver. Bile is concentrated and stored in the gallbladder. [NIH] Gamma irradiation: A type of radiation therapy that uses gamma radiation. Gamma radiation is a type of high-energy radiation that is different from x-rays. [NIH] Gamma Rays: Very powerful and penetrating, high-energy electromagnetic radiation of shorter wavelength than that of x-rays. They are emitted by a decaying nucleus, usually between 0.01 and 10 MeV. They are also called nuclear x-rays. [NIH] Ganglia: Clusters of multipolar neurons surrounded by a capsule of loosely organized connective tissue located outside the central nervous system. [NIH] Ganglion: 1. A knot, or knotlike mass. 2. A general term for a group of nerve cell bodies located outside the central nervous system; occasionally applied to certain nuclear groups within the brain or spinal cord, e.g. basal ganglia. 3. A benign cystic tumour occurring on a aponeurosis or tendon, as in the wrist or dorsum of the foot; it consists of a thin fibrous capsule enclosing a clear mucinous fluid. [EU] Gas: Air that comes from normal breakdown of food. The gases are passed out of the body through the rectum (flatus) or the mouth (burp). [NIH] 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 Emptying: The evacuation of food from the stomach into the duodenum. [NIH] Gastric Juices: Liquids produced in the stomach to help break down food and kill bacteria. [NIH]
Gastric Mucosa: Surface epithelium in the stomach that invaginates into the lamina propria, forming gastric pits. Tubular glands, characteristic of each region of the stomach (cardiac,
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gastric, and pyloric), empty into the gastric pits. The gastric mucosa is made up of several different kinds of cells. [NIH] Gastrin: A hormone released after eating. Gastrin causes the stomach to produce more acid. [NIH]
Gastroduodenal: Pertaining to or communicating with the stomach and duodenum, as a gastroduodenal fistula. [EU] Gastroenteritis: An acute inflammation of the lining of the stomach and intestines, characterized by anorexia, nausea, diarrhoea, abdominal pain, and weakness, which has various causes, including food poisoning due to infection with such organisms as Escherichia coli, Staphylococcus aureus, and Salmonella species; consumption of irritating food or drink; or psychological factors such as anger, stress, and fear. Called also enterogastritis. [EU] Gastrointestinal: Refers to the stomach and intestines. [NIH] Gastrointestinal tract: The stomach and intestines. [NIH] Gelatin: A product formed from skin, white connective tissue, or bone collagen. It is used as a protein food adjuvant, plasma substitute, hemostatic, suspending agent in pharmaceutical preparations, and in the manufacturing of capsules and suppositories. [NIH] Gelatinase A: A secreted endopeptidase homologous with interstitial collagenase, but which possesses an additional fibronectin-like domain. EC 3.4.24.24. [NIH] Gemcitabine: An anticancer drug that belongs to the family of drugs called antimetabolites. [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] Gene Therapy: The introduction of new genes into cells for the purpose of treating disease by restoring or adding gene expression. Techniques include insertion of retroviral vectors, transfection, homologous recombination, and injection of new genes into the nuclei of single cell embryos. The entire gene therapy process may consist of multiple steps. The new genes may be introduced into proliferating cells in vivo (e.g., bone marrow) or in vitro (e.g., fibroblast cultures) and the modified cells transferred to the site where the gene expression is required. Gene therapy may be particularly useful for treating enzyme deficiency diseases, hemoglobinopathies, and leukemias and may also prove useful in restoring drug sensitivity, particularly for leukemia. [NIH] Genetic Code: The specifications for how information, stored in nucleic acid sequence (base sequence), is translated into protein sequence (amino acid sequence). The start, stop, and order of amino acids of a protein is specified by consecutive triplets of nucleotides called codons (codon). [NIH] Genetic Engineering: Directed modification of the gene complement of a living organism by such techniques as altering the DNA, substituting genetic material by means of a virus, transplanting whole nuclei, transplanting cell hybrids, etc. [NIH] Genetics: The biological science that deals with the phenomena and mechanisms of heredity. [NIH]
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Genistein: An isoflavonoid derived from soy products. It inhibits protein-tyrosine kinase and topoisomerase-ii (dna topoisomerase (atp-hydrolysing)) activity and is used as an antineoplastic and antitumor agent. Experimentally, it has been shown to induce G2 phase arrest in human and murine cell lines. [NIH] Genital: Pertaining to the genitalia. [EU] Genotype: The genetic constitution of the individual; the characterization of the genes. [NIH] Germ Cells: The reproductive cells in multicellular organisms. [NIH] Gestation: The period of development of the young in viviparous animals, from the time of fertilization of the ovum until birth. [EU] Gestational: Psychosis attributable to or occurring during pregnancy. [NIH] Gestational Age: Age of the conceptus. In humans, this may be assessed by medical history, physical examination, early immunologic pregnancy tests, radiography, ultrasonography, and amniotic fluid analysis. [NIH] Ginseng: An araliaceous genus of plants that contains a number of pharmacologically active agents used as stimulants, sedatives, and tonics, especially in traditional medicine. [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] Glioma: A cancer of the brain that comes from glial, or supportive, cells. [NIH] Gliosarcoma: A type of glioma. [NIH] Glomerular: Pertaining to or of the nature of a glomerulus, especially a renal glomerulus. [EU]
Glomerulus: A tiny set of looping blood vessels in the nephron where blood is filtered in the kidney. [NIH] Glucans: Polysaccharides composed of repeating glucose units. They can consist of branched or unbranched chains in any linkages. [NIH] Glucocorticoid: A compound that belongs to the family of compounds called corticosteroids (steroids). Glucocorticoids affect metabolism and have anti-inflammatory and immunosuppressive effects. They may be naturally produced (hormones) or synthetic (drugs). [NIH] Glucose: D-Glucose. A primary source of energy for living organisms. It is naturally occurring and is found in fruits and other parts of plants in its free state. It is used therapeutically in fluid and nutrient replacement. [NIH] Glucose tolerance: The power of the normal liver to absorb and store large quantities of glucose and the effectiveness of intestinal absorption of glucose. The glucose tolerance test is a metabolic test of carbohydrate tolerance that measures active insulin, a hepatic function based on the ability of the liver to absorb glucose. The test consists of ingesting 100 grams of glucose into a fasting stomach; blood sugar should return to normal in 2 to 21 hours after ingestion. [NIH] Glucose Tolerance Test: Determination of whole blood or plasma sugar in a fasting state before and at prescribed intervals (usually 1/2 hr, 1 hr, 3 hr, 4 hr) after taking a specified amount (usually 100 gm orally) of glucose. [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]
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Glutamic Acid: A non-essential amino acid naturally occurring in the L-form. Glutamic acid (glutamate) is the most common excitatory neurotransmitter in the central nervous system. [NIH]
Glutamine: A non-essential amino acid present abundantly throught the body and is involved in many metabolic processes. It is synthesized from glutamic acid and ammonia. It is the principal carrier of nitrogen in the body and is an important energy source for many cells. [NIH] Glutathione Peroxidase: An enzyme catalyzing the oxidation of 2 moles of glutathione in the presence of hydrogen peroxide to yield oxidized glutathione and water. EC 1.11.1.9. [NIH]
Glycerol: A trihydroxy sugar alcohol that is an intermediate in carbohydrate and lipid metabolism. It is used as a solvent, emollient, pharmaceutical agent, and sweetening agent. [NIH]
Glycerophospholipids: Derivatives of phosphatidic acid in which the hydrophobic regions are composed of two fatty acids and a polar alcohol is joined to the C-3 position of glycerol through a phosphodiester bond. They are named according to their polar head groups, such as phosphatidylcholine and phosphatidylethanolamine. [NIH] Glycine: A non-essential amino acid. It is found primarily in gelatin and silk fibroin and used therapeutically as a nutrient. It is also a fast inhibitory neurotransmitter. [NIH] Glycogen: A sugar stored in the liver and muscles. It releases glucose into the blood when cells need it for energy. Glycogen is the chief source of stored fuel in the body. [NIH] Glycogen Synthase: An enzyme that catalyzes the transfer of D-glucose from UDPglucose into 1,4-alpha-D-glucosyl chains. EC 2.4.1.11. [NIH] Glycoprotein: A protein that has sugar molecules attached to it. [NIH] Glycosaminoglycan: A type of long, unbranched polysaccharide molecule. Glycosaminoglycans are major structural components of cartilage and are also found in the cornea of the eye. [NIH] 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] Glycyrrhetinic Acid: 3-beta-Hydroxy-11-oxoolean-12-en-30-oic acid. A product from Glycyrrhiza glabra L. Leguminosae with some antiallergic, antibacterial, and antiviral properties. It is used topically for allergic or infectious skin inflammation and orally for its aldosterone effects in electrolyte regulation. [NIH] Goblet Cells: Cells of the epithelial lining that produce and secrete mucins. [NIH] Gonadal: Pertaining to a gonad. [EU] Gonadotropin: The water-soluble follicle stimulating substance, by some believed to originate in chorionic tissue, obtained from the serum of pregnant mares. It is used to supplement the action of estrogens. [NIH] Governing Board: The group in which legal authority is vested for the control of healthrelated institutions and organizations. [NIH]
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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] Graft Rejection: An immune response with both cellular and humoral components, directed against an allogeneic transplant, whose tissue antigens are not compatible with those of the recipient. [NIH] Grafting: The operation of transfer of tissue from one site to another. [NIH] Gramicidin: Antibiotic mixture that is one of the two principle components of tyrothricin from Bacillus brevis. Gramicidin C or S is a cyclic, ten-amino acid polypeptide and gramicidins A, B, D, etc., seem to be linear polypeptides. The mixture is used topically for gram-positive organisms. It is toxic to blood, liver, kidneys, meninges, and the olfactory apparatus. [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] Granisetron: A serotonin receptor (5HT-3 selective) antagonist that has been used as an antiemetic for cancer chemotherapy patients. [NIH] Granulocyte: A type of white blood cell that fights bacterial infection. Neutrophils, eosinophils, and basophils are granulocytes. [NIH] Granulocyte-Macrophage Colony-Stimulating Factor: An acidic glycoprotein of MW 23 kDa with internal disulfide bonds. The protein is produced in response to a number of inflammatory mediators by mesenchymal cells present in the hemopoietic environment and at peripheral sites of inflammation. GM-CSF is able to stimulate the production of neutrophilic granulocytes, macrophages, and mixed granulocyte-macrophage colonies from bone marrow cells and can stimulate the formation of eosinophil colonies from fetal liver progenitor cells. GM-CSF can also stimulate some functional activities in mature granulocytes and macrophages. [NIH] Granulosa Cells: Cells of the membrana granulosa lining the vesicular ovarian follicle which become luteal cells after ovulation. [NIH] Growth: The progressive development of a living being or part of an organism from its earliest stage to maturity. [NIH] Growth factors: Substances made by the body that function to regulate cell division and cell survival. Some growth factors are also produced in the laboratory and used in biological therapy. [NIH] Growth Plate: The area between the epiphysis and the diaphysis within which bone growth occurs. [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] Guinea Pigs: A common name used for the family Caviidae. The most common species is Cavia porcellus which is the domesticated guinea pig used for pets and biomedical research. [NIH]
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Gynaecological: Pertaining to gynaecology. [EU] Gyrase: An enzyme that causes negative supercoiling of E. coli DNA during replication. [NIH]
Haematemesis: The vomiting of blood. [EU] Hair Cells: Mechanoreceptors located in the organ of Corti that are sensitive to auditory stimuli and in the vestibular apparatus that are sensitive to movement of the head. In each case the accessory sensory structures are arranged so that appropriate stimuli cause movement of the hair-like projections (stereocilia and kinocilia) which relay the information centrally in the nervous system. [NIH] Hair follicles: Shafts or openings on the surface of the skin through which hair grows. [NIH] Half-Life: The time it takes for a substance (drug, radioactive nuclide, or other) to lose half of its pharmacologic, physiologic, or radiologic activity. [NIH] 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] Heart attack: A seizure of weak or abnormal functioning of the heart. [NIH] Heart failure: Loss of pumping ability by the heart, often accompanied by fatigue, breathlessness, and excess fluid accumulation in body tissues. [NIH] Helminths: Commonly known as parasitic worms, this group includes the acanthocephala, nematoda, and platyhelminths. Some authors consider certain species of leeches that can become temporarily parasitic as helminths. [NIH] Hematogenous: Originating in the blood or spread through the bloodstream. [NIH] Hematologic malignancies: Cancers of the blood or bone marrow, including leukemia and lymphoma. Also called hematologic cancers. [NIH] Hematoma: An extravasation of blood localized in an organ, space, or tissue. [NIH] Hematopoiesis: The development and formation of various types of blood cells. [NIH] Heme: The color-furnishing portion of hemoglobin. It is found free in tissues and as the prosthetic group in many hemeproteins. [NIH] Hemoglobin: One of the fractions of glycosylated hemoglobin A1c. Glycosylated hemoglobin is formed when linkages of glucose and related monosaccharides bind to hemoglobin A and its concentration represents the average blood glucose level over the previous several weeks. HbA1c levels are used as a measure of long-term control of plasma glucose (normal, 4 to 6 percent). In controlled diabetes mellitus, the concentration of glycosylated hemoglobin A is within the normal range, but in uncontrolled cases the level may be 3 to 4 times the normal conentration. Generally, complications are substantially lower among patients with Hb levels of 7 percent or less than in patients with HbA1c levels of 9 percent or more. [NIH]
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Hemoglobinopathies: A group of inherited disorders characterized by structural alterations within the hemoglobin molecule. [NIH] Hemoglobinuria: The presence of free hemoglobin in the urine. [NIH] Hemorrhage: Bleeding or escape of blood from a vessel. [NIH] Hemostasis: The process which spontaneously arrests the flow of blood from vessels carrying blood under pressure. It is accomplished by contraction of the vessels, adhesion and aggregation of formed blood elements, and the process of blood or plasma coagulation. [NIH]
Heparin: Heparinic acid. A highly acidic mucopolysaccharide formed of equal parts of sulfated D-glucosamine and D-glucuronic acid with sulfaminic bridges. The molecular weight ranges from six to twenty thousand. Heparin occurs in and is obtained from liver, lung, mast cells, etc., of vertebrates. Its function is unknown, but it is used to prevent blood clotting in vivo and vitro, in the form of many different salts. [NIH] Hepatic: Refers to the liver. [NIH] Hepatitis: Inflammation of the liver and liver disease involving degenerative or necrotic alterations of hepatocytes. [NIH] Hepatocellular: Pertaining to or affecting liver cells. [EU] Hepatocyte: A liver cell. [NIH] Hepatocyte Growth Factor: Multifunctional growth factor which regulates both cell growth and cell motility. It exerts a strong mitogenic effect on hepatocytes and primary epithelial cells. Its receptor is proto-oncogene protein C-met. [NIH] Hepatotoxicity: How much damage a medicine or other substance does to the liver. [NIH] Hereditary: Of, relating to, or denoting factors that can be transmitted genetically from one generation to another. [NIH] Heredity: 1. The genetic transmission of a particular quality or trait from parent to offspring. 2. The genetic constitution of an individual. [EU] Herpes: Any inflammatory skin disease caused by a herpesvirus and characterized by the formation of clusters of small vesicles. When used alone, the term may refer to herpes simplex or to herpes zoster. [EU] Herpes Zoster: Acute vesicular inflammation. [NIH] Heterodimers: Zippered pair of nonidentical proteins. [NIH] Heterogeneity: The property of one or more samples or populations which implies that they are not identical in respect of some or all of their parameters, e. g. heterogeneity of variance. [NIH]
Heterotropia: One in which the angle of squint remains relatively unaltered on conjugate movement of the eyes. [NIH] Heterozygotes: Having unlike alleles at one or more corresponding loci on homologous chromosomes. [NIH] Hibernation: The dormant state in which some animal species pass the winter. It is characterized by narcosis and by sharp reduction in body temperature and metabolic activity and by a depression of vital signs. It is a natural physiological process in many warm-blooded animals. [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]
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Hirsutism: Excess hair in females and children with an adult male pattern of distribution. The concept does not include hypertrichosis, which is localized or generalized excess hair. [NIH]
Histamine: 1H-Imidazole-4-ethanamine. A depressor amine derived by enzymatic decarboxylation of histidine. It is a powerful stimulant of gastric secretion, a constrictor of bronchial smooth muscle, a vasodilator, and also a centrally acting neurotransmitter. [NIH] Histocompatibility: The degree of antigenic similarity between the tissues of different individuals, which determines the acceptance or rejection of allografts. [NIH] Histocompatibility Antigens: A group of antigens that includes both the major and minor histocompatibility antigens. The former are genetically determined by the major histocompatibility complex. They determine tissue type for transplantation and cause allograft rejections. The latter are systems of allelic alloantigens that can cause weak transplant rejection. [NIH] Histology: The study of tissues and cells under a microscope. [NIH] Hoarseness: An unnaturally deep or rough quality of voice. [NIH] Holocaust: A massive slaughter, especially the systematic mass extermination of European Jews in Nazi concentration camps prior to and during World War II. [NIH] Homeostasis: The processes whereby the internal environment of an organism tends to remain balanced and stable. [NIH] Homologous: Corresponding in structure, position, origin, etc., as (a) the feathers of a bird and the scales of a fish, (b) antigen and its specific antibody, (c) allelic chromosomes. [EU] Hormonal: Pertaining to or of the nature of a hormone. [EU] Hormone: A substance in the body that regulates certain organs. Hormones such as gastrin help in breaking down food. Some hormones come from cells in the stomach and small intestine. [NIH] Hormone therapy: Treatment of cancer by removing, blocking, or adding hormones. Also called endocrine therapy. [NIH] Host: Any animal that receives a transplanted graft. [NIH] Human papillomavirus: HPV. A virus that causes abnormal tissue growth (warts) and is often associated with some types of cancer. [NIH] Hyaluronidase: An enzyme that splits hyaluronic acid and thus lowers the viscosity of the acid and facilitates the spreading of fluids through tissues either advantageously or disadvantageously. [NIH] Hybrid: Cross fertilization between two varieties or, more usually, two species of vines, see also crossing. [NIH] Hybridization: The genetic process of crossbreeding to produce a hybrid. Hybrid nucleic acids can be formed by nucleic acid hybridization of DNA and RNA molecules. Protein hybridization allows for hybrid proteins to be formed from polypeptide chains. [NIH] Hybridoma: A hybrid cell resulting from the fusion of a specific antibody-producing spleen cell with a myeloma cell. [NIH] Hydrocortisone: The main glucocorticoid secreted by the adrenal cortex. Its synthetic counterpart is used, either as an injection or topically, in the treatment of inflammation, allergy, collagen diseases, asthma, adrenocortical deficiency, shock, and some neoplastic 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,
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odorless, tasteless, diatomic gas. Hydrogen ions are protons. Besides the common H1 isotope, hydrogen exists as the stable isotope deuterium and the unstable, radioactive isotope tritium. [NIH] Hydrogen Peroxide: A strong oxidizing agent used in aqueous solution as a ripening agent, bleach, and topical anti-infective. It is relatively unstable and solutions deteriorate over time unless stabilized by the addition of acetanilide or similar organic materials. [NIH] Hydrolases: Any member of the class of enzymes that catalyze the cleavage of the substrate and the addition of water to the resulting molecules, e.g., esterases, glycosidases (glycoside hydrolases), lipases, nucleotidases, peptidases (peptide hydrolases), and phosphatases (phosphoric monoester hydrolases). EC 3. [NIH] Hydrolysis: The process of cleaving a chemical compound by the addition of a molecule of water. [NIH] Hydroxyeicosatetraenoic Acids: Eicosatetraenoic acids substituted in any position by one or more hydroxy groups. They are important intermediates in a series of biosynthetic processes leading from arachidonic acid to a number of biologically active compounds such as prostaglandins, thromboxanes, and leukotrienes. [NIH] Hydroxylation: Hydroxylate, to introduce hydroxyl into (a compound or radical) usually by replacement of hydrogen. [EU] Hydroxylysine: A hydroxylated derivative of the amino acid lysine that is present in certain collagens. [NIH] Hydroxyproline: A hydroxylated form of the imino acid proline. A deficiency in ascorbic acid can result in impaired hydroxyproline formation. [NIH] Hyperalgesia: Excessive sensitiveness or sensibility to pain. [EU] Hyperandrogenism: A state characterized or caused by an excessive secretion of androgens by the adrenal cortex, ovaries, or testes. The clinical significance in males is negligible, so the term is used most commonly with reference to the female. The common manifestations in women are hirsutism and virilism. It is often caused by ovarian disease (particularly the polycystic ovary syndrome) and by adrenal diseases (particularly adrenal gland hyperfunction). [NIH] Hypercalcemia: Abnormally high level of calcium in the blood. [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] Hypersecretion: Excessive secretion. [EU] 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] Hypertrichosis: Localized or generalized excess hair. The concept does not include hirsutism, which is excess hair in females and children with an adult male pattern of distribution. [NIH] Hypertrophic cardiomyopathy: Heart muscle disease that leads to thickening of the heart walls, interfering with the heart's ability to fill with and pump blood. [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]
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Hypnotic: A drug that acts to induce sleep. [EU] Hypogonadism: Condition resulting from or characterized by abnormally decreased functional activity of the gonads, with retardation of growth and sexual development. [NIH] Hypotensive: Characterized by or causing diminished tension or pressure, as abnormally low blood pressure. [EU] Hypothalamic: Of or involving the hypothalamus. [EU] Hypothalamus: Ventral part of the diencephalon extending from the region of the optic chiasm to the caudal border of the mammillary bodies and forming the inferior and lateral walls of the third ventricle. [NIH] Hypoxia: Reduction of oxygen supply to tissue below physiological levels despite adequate perfusion of the tissue by blood. [EU] Hysterotomy: An incision in the uterus, performed through either the abdomen or the vagina. [NIH] Id: The part of the personality structure which harbors the unconscious instinctive desires and strivings of the individual. [NIH] Idiopathic: Describes a disease of unknown cause. [NIH] Ileostomy: Surgical creation of an external opening into the ileum for fecal diversion or drainage. Loop or tube procedures are most often employed. [NIH] Ileum: The lower end of the small intestine. [NIH] Imidazole: C3H4N2. The ring is present in polybenzimidazoles. [NIH] Imipramine: The prototypical tricyclic antidepressant. It has been used in major depression, dysthymia, bipolar depression, attention-deficit disorders, agoraphobia, and panic disorders. It has less sedative effect than some other members of this therapeutic group. [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 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
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Immunodeficiency: The decreased ability of the body to fight infection and disease. [NIH] 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] Immunophilins: Members of a family of highly conserved proteins which are all cis-trans peptidyl-prolyl isomerases (peptidylprolyl isomerase). They bind the immunosuppressant drugs cyclosporine; tacrolimus and sirolimus. They possess rotomase activity, which is inhibited by the immunosuppressant drugs that bind to them. EC 5.2.1.- [NIH] Immunosuppressant: An agent capable of suppressing immune responses. [EU]
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Immunosuppressive: Describes the ability to lower immune system responses. [NIH] Immunosuppressive Agents: Agents that suppress immune function by one of several mechanisms of action. Classical cytotoxic immunosuppressants act by inhibiting DNA synthesis. Others may act through activation of suppressor T-cell populations or by inhibiting the activation of helper cells. While immunosuppression has been brought about in the past primarily to prevent rejection of transplanted organs, new applications involving mediation of the effects of interleukins and other cytokines are emerging. [NIH] Immunotherapy: Manipulation of the host's immune system in treatment of disease. It includes both active and passive immunization as well as immunosuppressive therapy to prevent graft rejection. [NIH] Impairment: In the context of health experience, an impairment is any loss or abnormality of psychological, physiological, or anatomical structure or function. [NIH] Implant radiation: A procedure in which radioactive material sealed in needles, seeds, wires, or catheters is placed directly into or near the tumor. Also called [NIH] Implantation: The insertion or grafting into the body of biological, living, inert, or radioactive material. [EU] In situ: In the natural or normal place; confined to the site of origin without invasion of neighbouring tissues. [EU] In Situ Hybridization: A technique that localizes specific nucleic acid sequences within intact chromosomes, eukaryotic cells, or bacterial cells through the use of specific nucleic acid-labeled probes. [NIH] In vitro: In the laboratory (outside the body). The opposite of in vivo (in the body). [NIH] In vivo: In the body. The opposite of in vitro (outside the body or in the laboratory). [NIH] Incision: A cut made in the body during surgery. [NIH] Incontinence: Inability to control the flow of urine from the bladder (urinary incontinence) or the escape of stool from the rectum (fecal incontinence). [NIH] Indicative: That indicates; that points out more or less exactly; that reveals fairly clearly. [EU] Indolent: A type of cancer that grows slowly. [NIH] Indolent lymphoma: Lymphoma that grows slowly and has few symptoms. [NIH] Indomethacin: A non-steroidal anti-inflammatory agent (NSAID) that inhibits the enzyme cyclooxygenase necessary for the formation of prostaglandins and other autacoids. It also inhibits the motility of polymorphonuclear leukocytes. [NIH] Induction: The act or process of inducing or causing to occur, especially the production of a specific morphogenetic effect in the developing embryo through the influence of evocators or organizers, or the production of anaesthesia or unconsciousness by use of appropriate agents. [EU] Induction therapy: Treatment designed to be used as a first step toward shrinking the cancer and in evaluating response to drugs and other agents. Induction therapy is followed by additional therapy to eliminate whatever cancer remains. [NIH] Infarction: A pathological process consisting of a sudden insufficient blood supply to an area, which results in necrosis of that area. It is usually caused by a thrombus, an embolus, or a vascular torsion. [NIH] Infection: 1. Invasion and multiplication of microorganisms in body tissues, which may be clinically unapparent or result in local cellular injury due to competitive metabolism, toxins, intracellular replication, or antigen-antibody response. The infection may remain localized, subclinical, and temporary if the body's defensive mechanisms are effective. A local
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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]
Infestation: Parasitic attack or subsistence on the skin and/or its appendages, as by insects, mites, or ticks; sometimes used to denote parasitic invasion of the organs and tissues, as by helminths. [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] Informed Consent: Voluntary authorization, given to the physician by the patient, with full comprehension of the risks involved, for diagnostic or investigative procedures and medical and surgical treatment. [NIH] Infuse: To pour (a liquid) into something. [EU] 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] Inlay: In dentistry, a filling first made to correspond with the form of a dental cavity and then cemented into the cavity. [NIH] Inner ear: The labyrinth, comprising the vestibule, cochlea, and semicircular canals. [NIH] Innervation: 1. The distribution or supply of nerves to a part. 2. The supply of nervous energy or of nerve stimulus sent to a part. [EU] Inorganic: Pertaining to substances not of organic origin. [EU] Inositol: An isomer of glucose that has traditionally been considered to be a B vitamin although it has an uncertain status as a vitamin and a deficiency syndrome has not been identified in man. (From Martindale, The Extra Pharmacopoeia, 30th ed, p1379) Inositol phospholipids are important in signal transduction. [NIH] Insecticides: Pesticides designed to control insects that are harmful to man. The insects may be directly harmful, as those acting as disease vectors, or indirectly harmful, as destroyers of crops, food products, or textile fabrics. [NIH] Insight: The capacity to understand one's own motives, to be aware of one's own psychodynamics, to appreciate the meaning of symbolic behavior. [NIH] Insomnia: Difficulty in going to sleep or getting enough sleep. [NIH] 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]
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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] Insulin-like: Muscular growth factor. [NIH] Integrins: A family of transmembrane glycoproteins consisting of noncovalent heterodimers. They interact with a wide variety of ligands including extracellular matrix glycoproteins, complement, and other cells, while their intracellular domains interact with the cytoskeleton. The integrins consist of at least three identified families: the cytoadhesin receptors, the leukocyte adhesion receptors, and the very-late-antigen receptors. Each family contains a common beta-subunit combined with one or more distinct alpha-subunits. These receptors participate in cell-matrix and cell-cell adhesion in many physiologically important processes, including embryological development, hemostasis, thrombosis, wound healing, immune and nonimmune defense mechanisms, and oncogenic transformation. [NIH] Intensive Care: Advanced and highly specialized care provided to medical or surgical patients whose conditions are life-threatening and require comprehensive care and constant monitoring. It is usually administered in specially equipped units of a health care facility. [NIH]
Intensive Care Units: Hospital units providing continuous surveillance and care to acutely ill patients. [NIH] Intercostal: Situated between the ribs. [EU] Interferon: A biological response modifier (a substance that can improve the body's natural response to disease). Interferons interfere with the division of cancer cells and can slow tumor growth. There are several types of interferons, including interferon-alpha, -beta, and gamma. These substances are normally produced by the body. They are also made in the laboratory for use in treating cancer and other diseases. [NIH] Interferon-alpha: One of the type I interferons produced by peripheral blood leukocytes or lymphoblastoid cells when exposed to live or inactivated virus, double-stranded RNA, or bacterial products. It is the major interferon produced by virus-induced leukocyte cultures and, in addition to its pronounced antiviral activity, it causes activation of NK cells. [NIH] Interleukin-1: A soluble factor produced by monocytes, macrophages, and other cells which activates T-lymphocytes and potentiates their response to mitogens or antigens. IL-1 consists of two distinct forms, IL-1 alpha and IL-1 beta which perform the same functions but are distinct proteins. The biological effects of IL-1 include the ability to replace macrophage requirements for T-cell activation. The factor is distinct from interleukin-2. [NIH] Interleukin-10: Factor that is a coregulator of mast cell growth. It is produced by T-cells and B-cells and shows extensive homology with the Epstein-Barr virus BCRFI gene. [NIH] Interleukin-13: T-lymphocyte-derived cytokine that produces proliferation, immunoglobulin isotype switching, and immunoglobulin production by immature Blymphocytes. It appears to play a role in regulating inflammatory and immune responses. [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-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]
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Interleukin-5: Factor promoting eosinophil differentiation and activation in hematopoiesis. It also triggers activated B-cells for a terminal differentiation into Ig-secreting cells. [NIH] Interleukin-6: Factor that stimulates the growth and differentiation of human B-cells and is also a growth factor for hybridomas and plasmacytomas. It is produced by many different cells including T-cells, monocytes, and fibroblasts. [NIH] 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] Interleukins: Soluble factors which stimulate growth-related activities of leukocytes as well as other cell types. They enhance cell proliferation and differentiation, DNA synthesis, secretion of other biologically active molecules and responses to immune and inflammatory stimuli. [NIH] Intermittent: Occurring at separated intervals; having periods of cessation of activity. [EU] Internal Medicine: A medical specialty concerned with the diagnosis and treatment of diseases of the internal organ systems of adults. [NIH] Internal radiation: A procedure in which radioactive material sealed in needles, seeds, wires, or catheters is placed directly into or near the tumor. Also called brachytherapy, implant radiation, or interstitial radiation therapy. [NIH] Interstitial: Pertaining to or situated between parts or in the interspaces of a tissue. [EU] Interstitial Collagenase: A member of the metalloproteinase family of enzymes that is principally responsible for cleaving fibrillar collagen. It can degrade interstitial collagens, types I, II and III. EC 3.4.24.7. [NIH] Intestinal: Having to do with the intestines. [NIH] Intestinal Mucosa: The surface lining of the intestines where the cells absorb nutrients. [NIH] Intestine: A long, tube-shaped organ in the abdomen that completes the process of digestion. There is both a large intestine and a small intestine. Also called the bowel. [NIH] Intoxication: Poisoning, the state of being poisoned. [EU] Intracellular: Inside a cell. [NIH] Intramuscular: IM. Within or into muscle. [NIH] Intramuscular injection: IM. Injection into a muscle. [NIH] Intraocular: Within the eye. [EU] Intraocular pressure: Pressure of the fluid inside the eye; normal IOP varies among individuals. [NIH] Intravascular: Within a vessel or vessels. [EU] 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] Ion Exchange: Reversible chemical reaction between a solid, often an ION exchange resin, and a fluid whereby ions may be exchanged from one substance to another. This technique
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is used in water purification, in research, and in industry. [NIH] Ion Transport: The movement of ions across energy-transducing cell membranes. Transport can be active or passive. Passive ion transport (facilitated diffusion) derives its energy from the concentration gradient of the ion itself and allows the transport of a single solute in one direction (uniport). Active ion transport is usually coupled to an energy-yielding chemical or photochemical reaction such as ATP hydrolysis. This form of primary active transport is called an ion pump. Secondary active transport utilizes the voltage and ion gradients produced by the primary transport to drive the cotransport of other ions or molecules. These may be transported in the same (symport) or opposite (antiport) direction. [NIH] Ionization: 1. Any process by which a neutral atom gains or loses electrons, thus acquiring a net charge, as the dissociation of a substance in solution into ions or ion production by the passage of radioactive particles. 2. Iontophoresis. [EU] Ionizing: Radiation comprising charged particles, e. g. electrons, protons, alpha-particles, etc., having sufficient kinetic energy to produce ionization by collision. [NIH] Ions: An atom or group of atoms that have a positive or negative electric charge due to a gain (negative charge) or loss (positive charge) of one or more electrons. Atoms with a positive charge are known as cations; those with a negative charge are anions. [NIH] Iontophoresis: Therapeutic introduction of ions of soluble salts into tissues by means of electric current. In medical literature it is commonly used to indicate the process of increasing the penetration of drugs into surface tissues by the application of electric current. It has nothing to do with ion exchange, air ionization nor phonophoresis, none of which requires current. [NIH] Irinotecan: An anticancer drug that belongs to a family of anticancer drugs called topoisomerase inhibitors. It is a camptothecin analogue. Also called CPT 11. [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. 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] Ischemia: Deficiency of blood in a part, due to functional constriction or actual obstruction of a blood vessel. [EU] Isotretinoin: A topical dermatologic agent that is used in the treatment of acne vulgaris and several other skin diseases. The drug has teratogenic and other adverse effects. [NIH] Isozymes: The multiple forms of a single enzyme. [NIH] Jejunum: That portion of the small intestine which extends from the duodenum to the ileum; called also intestinum jejunum. [EU] 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]
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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] Keratoconjunctivitis: Simultaneous inflammation of the cornea and conjunctiva. [NIH] Ketoacidosis: Acidosis accompanied by the accumulation of ketone bodies (ketosis) in the body tissues and fluids, as in diabetic acidosis. [EU] Ketone Bodies: Chemicals that the body makes when there is not enough insulin in the blood and it must break down fat for its energy. Ketone bodies can poison and even kill body cells. When the body does not have the help of insulin, the ketones build up in the blood and then "spill" over into the urine so that the body can get rid of them. The body can also rid itself of one type of ketone, called acetone, through the lungs. This gives the breath a fruity odor. Ketones that build up in the body for a long time lead to serious illness and coma. [NIH] Ketorolac: A drug that belongs to a family of drugs called nonsteroidal anti-inflammatory agents. It is being studied in cancer prevention. [NIH] Ketorolac Tromethamine: A pyrrolizine carboxylic acid derivative structurally related to indomethacin. It is a non-steroidal anti-inflammatory agent used for analgesia for postoperative pain and inhibits cyclooxygenase activity. [NIH] Kidney Cortex: The outer zone of the kidney, beneath the capsule, consisting of kidney glomerulus; kidney tubules, distal; and kidney tubules, proximal. [NIH] Kidney Disease: Any one of several chronic conditions that are caused by damage to the cells of the kidney. People who have had diabetes for a long time may have kidney damage. Also called nephropathy. [NIH] Kinetic: Pertaining to or producing motion. [EU] Labile: 1. Gliding; moving from point to point over the surface; unstable; fluctuating. 2. Chemically unstable. [EU] Labyrinth: The internal ear; the essential part of the organ of hearing. It consists of an osseous and a membranous portion. [NIH] Lacrimal: Pertaining to the tears. [EU] Lacrimal gland: The small almond-shaped structure that produces tears; located just above the outer corner of the eye. [NIH] Lactate Dehydrogenase: A tetrameric enzyme that, along with the coenzyme NAD+, catalyzes the interconversion of lactate and pyruvate. In vertebrates, genes for three different subunits (LDH-A, LDH-B and LDH-C) exist. [NIH] Lactation: The period of the secretion of milk. [EU] Laminin: Large, noncollagenous glycoprotein with antigenic properties. It is localized in the basement membrane lamina lucida and functions to bind epithelial cells to the basement membrane. Evidence suggests that the protein plays a role in tumor invasion. [NIH] Large Intestine: The part of the intestine that goes from the cecum to the rectum. The large
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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] Lectin: A complex molecule that has both protein and sugars. Lectins are able to bind to the outside of a cell and cause biochemical changes in it. Lectins are made by both animals and plants. [NIH] Lens: The transparent, double convex (outward curve on both sides) structure suspended between the aqueous and vitreous; helps to focus light on the retina. [NIH] Leptin: A 16-kD peptide hormone secreted from white adipocytes and implicated in the regulation of food intake and energy balance. Leptin provides the key afferent signal from fat cells in the feedback system that controls body fat stores. [NIH] Lethal: Deadly, fatal. [EU] Leucine: An essential branched-chain amino acid important for hemoglobin formation. [NIH] Leucocyte: All the white cells of the blood and their precursors (myeloid cell series, lymphoid cell series) but commonly used to indicate granulocytes exclusive of lymphocytes. [NIH]
Leucovorin: The active metabolite of folic acid. Leucovorin is used principally as its calcium salt as an antidote to folic acid antagonists which block the conversion of folic acid to folinic acid. [NIH] Leukaemia: An acute or chronic disease of unknown cause in man and other warm-blooded animals that involves the blood-forming organs, is characterized by an abnormal increase in the number of leucocytes in the tissues of the body with or without a corresponding increase of those in the circulating blood, and is classified according of the type leucocyte most prominently involved. [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] Leukotrienes: A family of biologically active compounds derived from arachidonic acid by oxidative metabolism through the 5-lipoxygenase pathway. They participate in host defense reactions and pathophysiological conditions such as immediate hypersensitivity and inflammation. They have potent actions on many essential organs and systems, including the cardiovascular, pulmonary, and central nervous system as well as the gastrointestinal tract and the immune system. [NIH] Levobunolol: A nonselective beta-adrenoceptor antagonist used in the treatment of glaucoma. [NIH] Libido: The psychic drive or energy associated with sexual instinct in the broad sense (pleasure and love-object seeking). It may also connote the psychic energy associated with instincts in general that motivate behavior. [NIH] Library Services: Services offered to the library user. They include reference and circulation. [NIH]
Lidocaine: A local anesthetic and cardiac depressant used as an antiarrhythmia agent. Its
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actions are more intense and its effects more prolonged than those of procaine but its duration of action is shorter than that of bupivacaine or prilocaine. [NIH] Life cycle: The successive stages through which an organism passes from fertilized ovum or spore to the fertilized ovum or spore of the next generation. [NIH] Ligament: A band of fibrous tissue that connects bones or cartilages, serving to support and strengthen joints. [EU] Ligands: A RNA simulation method developed by the MIT. [NIH] 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] Linkage: The tendency of two or more genes in the same chromosome to remain together from one generation to the next more frequently than expected according to the law of independent assortment. [NIH] Lipid: Fat. [NIH] Lipid Peroxidation: Peroxidase catalyzed oxidation of lipids using hydrogen peroxide as an electron acceptor. [NIH] Lipophilic: Having an affinity for fat; pertaining to or characterized by lipophilia. [EU] Lipopolysaccharide: Substance consisting of polysaccaride and lipid. [NIH] 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]
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]
Litter: Appliance consisting of an oblong frame over which is stretched a canvas or other material, used for carrying an injured or disabled person. [NIH] Litter Size: The number of offspring produced at one birth by an animal. [NIH] Liver: A large, glandular organ located in the upper abdomen. The liver cleanses the blood and aids in digestion by secreting bile. [NIH] Liver cancer: A disease in which malignant (cancer) cells are found in the tissues of the liver. [NIH]
Liver metastases: Cancer that has spread from the original (primary) tumor to the liver. [NIH]
Liver Regeneration: Repair or renewal of hepatic tissue. [NIH] Localization: The process of determining or marking the location or site of a lesion or
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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] Lomustine: An alkylating agent of value against both hematologic malignancies and solid tumors. [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] Lovastatin: A fungal metabolite isolated from cultures of Aspergillus terreus. The compound is a potent anticholesteremic agent. It inhibits 3-hydroxy-3-methylglutaryl coenzyme A reductase (hydroxymethylglutaryl CoA reductases), which is the rate-limiting enzyme in cholesterol biosynthesis. It also stimulates the production of low-density lipoprotein receptors in the liver. [NIH] Low-density lipoprotein: Lipoprotein that contains most of the cholesterol in the blood. LDL carries cholesterol to the tissues of the body, including the arteries. A high level of LDL increases the risk of heart disease. LDL typically contains 60 to 70 percent of the total serum cholesterol and both are directly correlated with CHD risk. [NIH] Lucida: An instrument, invented by Wollaton, consisting essentially of a prism or a mirror through which an object can be viewed so as to appear on a plane surface seen in direct view and on which the outline of the object may be traced. [NIH] Lumbar: Pertaining to the loins, the part of the back between the thorax and the pelvis. [EU] Lumbar puncture: A procedure in which a needle is put into the lower part of the spinal column to collect cerebrospinal fluid or to give anticancer drugs intrathecally. Also called a spinal tap. [NIH] Lumen: The cavity or channel within a tube or tubular organ. [EU] Lupus: A form of cutaneous tuberculosis. It is seen predominantly in women and typically involves the nasal, buccal, and conjunctival mucosa. [NIH] Lutein Cells: The cells of the corpus luteum which are derived from the granulosa cells and the theca cells of the Graafian follicle. [NIH] Lymph: The almost colorless fluid that travels through the lymphatic system and carries cells that help fight infection and disease. [NIH] Lymph node: A rounded mass of lymphatic tissue that is surrounded by a capsule of connective tissue. Also known as a lymph gland. Lymph nodes are spread out along lymphatic vessels and contain many lymphocytes, which filter the lymphatic fluid (lymph). [NIH]
Lymphatic: The tissues and organs, including the bone marrow, spleen, thymus, and lymph nodes, that produce and store cells that fight infection and disease. [NIH] Lymphatic system: The tissues and organs that produce, store, and carry white blood cells that fight infection and other diseases. This system includes the bone marrow, spleen, thymus, lymph nodes and a network of thin tubes that carry lymph and white blood cells. These tubes branch, like blood vessels, into all the tissues of the body. [NIH] Lymphoblastic: One of the most aggressive types of non-Hodgkin lymphoma. [NIH] Lymphoblasts: Interferon produced predominantly by leucocyte cells. [NIH] Lymphocyte: A white blood cell. Lymphocytes have a number of roles in the immune system, including the production of antibodies and other substances that fight infection and
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diseases. [NIH] Lymphocyte Count: A count of the number of lymphocytes in the blood. [NIH] Lymphocytic: Referring to lymphocytes, a type of white blood cell. [NIH] Lymphoid: Referring to lymphocytes, a type of white blood cell. Also refers to tissue in which lymphocytes develop. [NIH] Lymphokines: Soluble protein factors generated by activated lymphocytes that affect other cells, primarily those involved in cellular immunity. [NIH] Lymphoma: A general term for various neoplastic diseases of the lymphoid tissue. [NIH] Lysine: An essential amino acid. It is often added to animal feed. [NIH] Lyssavirus: A genus of the family Rhabdoviridae that includes rabies virus and other rabieslike viruses. [NIH] Macroglia: A type of neuroglia composed of astrocytes. [NIH] Macrophage: A type of white blood cell that surrounds and kills microorganisms, removes dead cells, and stimulates the action of other immune system cells. [NIH] Macrophage Activation: The process of altering the morphology and functional activity of macrophages so that they become avidly phagocytic. It is initiated by lymphokines, such as the macrophage activation factor (MAF) and the macrophage migration-inhibitory factor (MMIF), immune complexes, C3b, and various peptides, polysaccharides, and immunologic adjuvants. [NIH] Macrophage Colony-Stimulating Factor: A mononuclear phagocyte colony-stimulating factor synthesized by mesenchymal cells. The compound stimulates the survival, proliferation, and differentiation of hematopoietic cells of the monocyte-macrophage series. M-CSF is a disulfide-bonded glycoprotein dimer with a MW of 70 kDa. It binds to a specific high affinity receptor (receptor, macrophage colony-stimulating factor). [NIH] Magnetic Resonance Imaging: Non-invasive method of demonstrating internal anatomy based on the principle that atomic nuclei in a strong magnetic field absorb pulses of radiofrequency energy and emit them as radiowaves which can be reconstructed into computerized images. The concept includes proton spin tomographic techniques. [NIH] Magnetic Resonance Spectroscopy: Spectroscopic method of measuring the magnetic moment of elementary particles such as atomic nuclei, protons or electrons. It is employed in clinical applications such as NMR Tomography (magnetic resonance imaging). [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] Malabsorption: Impaired intestinal absorption of nutrients. [EU] Malformation: A morphologic developmental process. [EU]
defect
resulting
from
an
intrinsically
abnormal
Malignancy: A cancerous tumor that can invade and destroy nearby tissue and spread to other parts of the body. [NIH] Malignant: Cancerous; a growth with a tendency to invade and destroy nearby tissue and spread to other parts of the body. [NIH]
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Malignant tumor: A tumor capable of metastasizing. [NIH] Malnutrition: A condition caused by not eating enough food or not eating a balanced diet. [NIH]
Mammary: Pertaining to the mamma, or breast. [EU] Mandible: The largest and strongest bone of the face constituting the lower jaw. It supports the lower teeth. [NIH] Mania: Excitement of psychotic proportions manifested by mental and physical hyperactivity, disorganization of behaviour, and elevation of mood. [EU] Manic: Affected with mania. [EU] Manifest: Being the part or aspect of a phenomenon that is directly observable : concretely expressed in behaviour. [EU] Mannans: Polysaccharides consisting of mannose units. [NIH] Mass Media: Instruments or technological means of communication that reach large numbers of people with a common message: press, radio, television, etc. [NIH] Mastectomy: Surgery to remove the breast (or as much of the breast tissue as possible). [NIH] Mastication: The act and process of chewing and grinding food in the mouth. [NIH] Matrix metalloproteinase: A member of a group of enzymes that can break down proteins, such as collagen, that are normally found in the spaces between cells in tissues (i.e., extracellular matrix proteins). Because these enzymes need zinc or calcium atoms to work properly, they are called metalloproteinases. Matrix metalloproteinases are involved in wound healing, angiogenesis, and tumor cell metastasis. [NIH] Maxillary: Pertaining to the maxilla : the irregularly shaped bone that with its fellow forms the upper jaw. [EU] Maxillary Nerve: The intermediate sensory division of the trigeminal (5th cranial) nerve. The maxillary nerve carries general afferents from the intermediate region of the face including the lower eyelid, nose and upper lip, the maxillary teeth, and parts of the dura. [NIH]
Maximum Tolerated Dose: The highest dose level eliciting signs of toxicity without having major effects on survival relative to the test in which it is used. [NIH] Measles Virus: The type species of morbillivirus and the cause of the highly infectious human disease measles, which affects mostly children. [NIH] Meatus: A canal running from the internal auditory foramen through the petrous portion of the temporal bone. It gives passage to the facial and auditory nerves together with the auditory branch of the basilar artery and the internal auditory veins. [NIH] Mechanoreceptors: Cells specialized to transduce mechanical stimuli and relay that information centrally in the nervous system. Mechanoreceptors include hair cells, which mediate hearing and balance, and the various somatosensory receptors, often with nonneural accessory structures. [NIH] Mechlorethamine: A vesicant and necrotizing irritant destructive to mucous membranes. It was formerly used as a war gas. The hydrochloride is used as an antineoplastic in Hodgkin's disease and lymphomas. It causes severe gastrointestinal and bone marrow damage. [NIH] Medial: Lying near the midsaggital plane of the body; opposed to lateral. [NIH] Mediate: Indirect; accomplished by the aid of an intervening medium. [EU] Mediator: An object or substance by which something is mediated, such as (1) a structure of the nervous system that transmits impulses eliciting a specific response; (2) a chemical
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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 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] Medullary: Pertaining to the marrow or to any medulla; resembling marrow. [EU] Megakaryocytes: Very large bone marrow cells which release mature blood platelets. [NIH] Melanin: The substance that gives the skin its color. [NIH] Melanocytes: Epidermal dendritic pigment cells which control long-term morphological color changes by alteration in their number or in the amount of pigment they produce and store in the pigment containing organelles called melanosomes. Melanophores are larger cells which do not exist in mammals. [NIH] Melanoma: A form of skin cancer that arises in melanocytes, the cells that produce pigment. Melanoma usually begins in a mole. [NIH] Melphalan: An alkylating nitrogen mustard that is used as an antineoplastic in the form of the levo isomer - melphalan, the racemic mixture - merphalan, and the dextro isomer medphalan; toxic to bone marrow, but little vesicant action; potential carcinogen. [NIH] Membrane: A very thin layer of tissue that covers a surface. [NIH] Membrane Glycoproteins: Glycoproteins found on the membrane or surface of cells. [NIH] Membrane Lipids: Lipids, predominantly phospholipids, cholesterol and small amounts of glycolipids found in membranes including cellular and intracellular membranes. These lipids may be arranged in bilayers in the membranes with integral proteins between the layers and peripheral proteins attached to the outside. Membrane lipids are required for active transport, several enzymatic activities and membrane formation. [NIH] 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] Menstrual Cycle: The period of the regularly recurring physiologic changes in the endometrium occurring during the reproductive period in human females and some primates and culminating in partial sloughing of the endometrium (menstruation). [NIH] Menstruation: The normal physiologic discharge through the vagina of blood and mucosal tissues from the nonpregnant uterus. [NIH] Mental: Pertaining to the mind; psychic. 2. (L. mentum chin) pertaining to the chin. [EU] Mental Disorders: Psychiatric illness or diseases manifested by breakdowns in the adaptational process expressed primarily as abnormalities of thought, feeling, and behavior producing either distress or impairment of function. [NIH] Mental Health: The state wherein the person is well adjusted. [NIH] Mental Processes: Conceptual functions or thinking in all its forms. [NIH] Mentors: Senior professionals who provide guidance, direction and support to those
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persons desirous of improvement in academic positions, administrative positions or other career development situations. [NIH] Mercaptopurine: An anticancer drug that belongs to the family of drugs called antimetabolites. [NIH] Mercury: A silver metallic element that exists as a liquid at room temperature. It has the atomic symbol Hg (from hydrargyrum, liquid silver), atomic number 80, and atomic weight 200.59. Mercury is used in many industrial applications and its salts have been employed therapeutically as purgatives, antisyphilitics, disinfectants, and astringents. It can be absorbed through the skin and mucous membranes which leads to mercury poisoning. Because of its toxicity, the clinical use of mercury and mercurials is diminishing. [NIH] Mesenchymal: Refers to cells that develop into connective tissue, blood vessels, and lymphatic tissue. [NIH] Mesoderm: The middle germ layer of the embryo. [NIH] Metabolic disorder: A condition in which normal metabolic processes are disrupted, usually because of a missing enzyme. [NIH] Metabolite: Any substance produced by metabolism or by a metabolic process. [EU] Metallothionein: A low-molecular-weight (approx. 10 kD) protein occurring in the cytoplasm of kidney cortex and liver. It is rich in cysteinyl residues and contains no aromatic amino acids. Metallothionein shows high affinity for bivalent heavy metals. [NIH] 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] Methazolamide: A carbonic anhydrase inhibitor that is used as a diuretic and in the treatment of glaucoma. [NIH] Methionine: A sulfur containing essential amino acid that is important in many body functions. It is a chelating agent for heavy metals. [NIH] Methotrexate: An antineoplastic antimetabolite with immunosuppressant properties. It is an inhibitor of dihydrofolate reductase and prevents the formation of tetrahydrofolate, necessary for synthesis of thymidylate, an essential component of DNA. [NIH] Methylprednisolone: (6 alpha,11 beta)-11,17,21-Trihydroxy-6-methylpregna-1,4-diene-3,2dione. A prednisolone derivative which has pharmacological actions similar to prednisolone. [NIH] Metoclopramide: A dopamine D2 antagonist that is used as an antiemetic. [NIH] MI: Myocardial infarction. Gross necrosis of the myocardium as a result of interruption of the blood supply to the area; it is almost always caused by atherosclerosis of the coronary arteries, upon which coronary thrombosis is usually superimposed. [NIH] Microbe: An organism which cannot be observed with the naked eye; e. g. unicellular animals, lower algae, lower fungi, bacteria. [NIH] Microbiology: The study of microorganisms such as fungi, bacteria, algae, archaea, and viruses. [NIH] Microglia: The third type of glial cell, along with astrocytes and oligodendrocytes (which together form the macroglia). Microglia vary in appearance depending on developmental stage, functional state, and anatomical location; subtype terms include ramified, perivascular, ameboid, resting, and activated. Microglia clearly are capable of phagocytosis
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and play an important role in a wide spectrum of neuropathologies. They have also been suggested to act in several other roles including in secretion (e.g., of cytokines and neural growth factors), in immunological processing (e.g., antigen presentation), and in central nervous system development and remodeling. [NIH] 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] Microtubules: Slender, cylindrical filaments found in the cytoskeleton of plant and animal cells. They are composed of the protein tubulin. [NIH] Migration: The systematic movement of genes between populations of the same species, geographic race, or variety. [NIH] Mineralization: The action of mineralizing; the state of being mineralized. [EU] Mineralocorticoid: 1. Any of the group of C21 corticosteroids, principally aldosterone, predominantly involved in the regulation of electrolyte and water balance through their effect on ion transport in epithelial cells of the renal tubules, resulting in retention of sodium and loss of potassium; some also possess varying degrees of glucocorticoid activity. Their secretion is regulated principally by plasma volume, serum potassium concentration and angiotensin II, and to a lesser extent by anterior pituitary ACTH. 2. Of, pertaining to, having the properties of, or resembling a mineralocorticoid. [EU] Minor Histocompatibility Antigens: Allelic alloantigens often responsible for weak graft rejection in cases when (major) histocompatibility has been established by standard tests. In the mouse they are coded by more than 500 genes at up to 30 minor histocompatibility loci. The most well-known minor histocompatibility antigen in mammals is the H-Y antigen. [NIH]
Miotic: 1. Pertaining to, characterized by, or producing miosis : contraction of the pupil. 2. An agent that causes the pupil to contract. 3. Meiotic: characterized by cell division. [EU] 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] Mitoxantrone: An anthracenedione-derived antineoplastic agent. [NIH] Mobility: Capability of movement, of being moved, or of flowing freely. [EU] Mobilization: The process of making a fixed part or stored substance mobile, as by separating a part from surrounding structures to make it accessible for an operative procedure or by causing release into the circulation for body use of a substance stored in the body. [EU] Modification: A change in an organism, or in a process in an organism, that is acquired from its own activity or environment. [NIH] 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]
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Monoamine: Enzyme that breaks down dopamine in the astrocytes and microglia. [NIH] Monoamine Oxidase: An enzyme that catalyzes the oxidative deamination of naturally occurring monoamines. It is a flavin-containing enzyme that is localized in mitochondrial membranes, whether in nerve terminals, the liver, or other organs. Monoamine oxidase is important in regulating the metabolic degradation of catecholamines and serotonin in neural or target tissues. Hepatic monoamine oxidase has a crucial defensive role in inactivating circulating monoamines or those, such as tyramine, that originate in the gut and are absorbed into the portal circulation. (From Goodman and Gilman's, The Pharmacological Basis of Therapeutics, 8th ed, p415) EC 1.4.3.4. [NIH] Monoclonal: An antibody produced by culturing a single type of cell. It therefore consists of a single species of immunoglobulin molecules. [NIH] Monoclonal antibodies: Laboratory-produced substances that can locate and bind to cancer cells wherever they are in the body. Many monoclonal antibodies are used in cancer detection or therapy; each one recognizes a different protein on certain cancer cells. Monoclonal antibodies can be used alone, or they can be used to deliver drugs, toxins, or radioactive material directly to a tumor. [NIH] Monocyte: A type of white blood cell. [NIH] Mononuclear: A cell with one nucleus. [NIH] Monophosphate: So called second messenger for neurotransmitters and hormones. [NIH] Mood Disorders: Those disorders that have a disturbance in mood as their predominant feature. [NIH] Morbillivirus: A genus of the family Paramyxoviridae (subfamily Paramyxovirinae) where all the virions have hemagglutinin but not neuraminidase activity. All members produce both cytoplasmic and intranuclear inclusion bodies. MEASLES VIRUS is the type species. [NIH]
Morphine: The principal alkaloid in opium and the prototype opiate analgesic and narcotic. Morphine has widespread effects in the central nervous system and on smooth muscle. [NIH] 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] 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] Mucosa: A mucous membrane, or tunica mucosa. [EU] Mucositis: A complication of some cancer therapies in which the lining of the digestive system becomes inflamed. Often seen as sores in the mouth. [NIH] Mucus: The viscous secretion of mucous membranes. It contains mucin, white blood cells, water, inorganic salts, and exfoliated cells. [NIH] Multidose: Occurring in, or using multiple doses. [EU] Multiple Myeloma: A malignant tumor of plasma cells usually arising in the bone marrow; characterized by diffuse involvement of the skeletal system, hyperglobulinemia, Bence-Jones proteinuria, and anemia. [NIH]
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Mumps Virus: The type species of rubulavirus that causes an acute infectious disease in humans, affecting mainly children. Transmission occurs by droplet infection. [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] Muscle relaxant: An agent that specifically aids in reducing muscle tension, as those acting at the polysynaptic neurons of motor nerves (e.g. meprobamate) or at the myoneural junction (curare and related compounds). [EU] Muscle Relaxation: That phase of a muscle twitch during which a muscle returns to a resting position. [NIH] Muscle Spindles: Mechanoreceptors found between skeletal muscle fibers. Muscle spindles are arranged in parallel with muscle fibers and respond to the passive stretch of the muscle, but cease to discharge if the muscle contracts isotonically, thus signaling muscle length. The muscle spindles are the receptors responsible for the stretch or myotactic reflex. [NIH] Muscular Atrophy: Derangement in size and number of muscle fibers occurring with aging, reduction in blood supply, or following immobilization, prolonged weightlessness, malnutrition, and particularly in denervation. [NIH] Muscular Dystrophies: A general term for a group of inherited disorders which are characterized by progressive degeneration of skeletal muscles. [NIH] Musculoskeletal System: Themuscles, bones, and cartilage of the body. [NIH] Mutagenic: Inducing genetic mutation. [EU] Myalgia: Pain in a muscle or muscles. [EU] Mydriatic: 1. Dilating the pupil. 2. Any drug that dilates the pupil. [EU] Myelodysplastic syndrome: Disease in which the bone marrow does not function normally. Also called preleukemia or smoldering leukemia. [NIH] Myelogenous: Produced by, or originating in, the bone marrow. [NIH] Myeloma: Cancer that arises in plasma cells, a type of white blood cell. [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] Myocarditis: Inflammation of the myocardium; inflammation of the muscular walls of the heart. [EU] Myocardium: The muscle tissue of the heart composed of striated, involuntary muscle known as cardiac muscle. [NIH] Myosin: Chief protein in muscle and the main constituent of the thick filaments of muscle fibers. In conjunction with actin, it is responsible for the contraction and relaxation of muscles. [NIH] Myotonic Dystrophy: A condition presenting muscle weakness and wasting which may be progressive. [NIH] Naloxone: A specific opiate antagonist that has no agonist activity. It is a competitive antagonist at mu, delta, and kappa opioid receptors. [NIH] Narcotic: 1. Pertaining to or producing narcosis. 2. An agent that produces insensibility or stupor, applied especially to the opioids, i.e. to any natural or synthetic drug that has morphine-like actions. [EU] Nasal Mucosa: The mucous membrane lining the nasal cavity. [NIH]
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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] Nebramycin: A complex of antibiotic substances produced by Streptomyces tenebrarius. [NIH]
Necrotizing Enterocolitis: A condition in which part of the tissue in the intestines is destroyed. Occurs mainly in under-weight newborn babies. A temporary ileostomy may be necessary. [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] Neomycin: Antibiotic complex produced by Streptomyces fradiae. It is composed of neomycins A, B, and C. It acts by inhibiting translation during protein synthesis. [NIH] Neonatal: Pertaining to the first four weeks after birth. [EU] Neoplasia: Abnormal and uncontrolled cell growth. [NIH] Neoplasm: A new growth of benign or malignant tissue. [NIH] Neoplastic: Pertaining to or like a neoplasm (= any new and abnormal growth); pertaining to neoplasia (= the formation of a neoplasm). [EU] Nephrology: A subspecialty of internal medicine concerned with the anatomy, physiology, and pathology of the kidney. [NIH] 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] Nephrotoxic: Toxic or destructive to kidney cells. [EU] Nerve: A cordlike structure of nervous tissue that connects parts of the nervous system with other tissues of the body and conveys nervous impulses to, or away from, these tissues. [NIH] Nerve Fibers: Slender processes of neurons, especially the prolonged axons that conduct nerve impulses. [NIH] Nerve Growth Factor: Nerve growth factor is the first of a series of neurotrophic factors that were found to influence the growth and differentiation of sympathetic and sensory neurons. It is comprised of alpha, beta, and gamma subunits. The beta subunit is responsible for its growth stimulating activity. [NIH] Nervous System: The entire nerve apparatus composed of the brain, spinal cord, nerves and ganglia. [NIH] 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] Neuralgia: Intense or aching pain that occurs along the course or distribution of a peripheral or cranial nerve. [NIH]
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Neuroanatomy: Study of the anatomy of the nervous system as a specialty or discipline. [NIH]
Neuroblastoma: Cancer that arises in immature nerve cells and affects mostly infants and children. [NIH] Neuroendocrine: Having to do with the interactions between the nervous system and the endocrine system. Describes certain cells that release hormones into the blood in response to stimulation of the nervous system. [NIH] Neuroendocrinology: The study of the anatomical and functional relationships between the nervous system and the endocrine system. [NIH] Neuroleptic: A term coined to refer to the effects on cognition and behaviour of antipsychotic drugs, which produce a state of apathy, lack of initiative, and limited range of emotion and in psychotic patients cause a reduction in confusion and agitation and normalization of psychomotor activity. [EU] Neuromuscular: Pertaining to muscles and nerves. [EU] 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] Neurosecretory Systems: A system of neurons that has the specialized function to produce and secrete hormones, and that constitutes, in whole or in part, an endocrine organ or system. [NIH] Neurosyphilis: A late form of syphilis that affects the brain and may lead to dementia and death. [NIH] Neurotoxic: Poisonous or destructive to nerve tissue. [EU] Neurotransmitter: Any of a group of substances that are released on excitation from the axon terminal of a presynaptic neuron of the central or peripheral nervous system and travel across the synaptic cleft to either excite or inhibit the target cell. Among the many substances that have the properties of a neurotransmitter are acetylcholine, norepinephrine, epinephrine, dopamine, glycine, y-aminobutyrate, glutamic acid, substance P, enkephalins, endorphins, and serotonin. [EU] Neurotrophins: A nerve growth factor. [NIH] Neurovegetative: Pertaining to the vegetative (autonomic) nervous system. [EU] Neutrons: Electrically neutral elementary particles found in all atomic nuclei except light hydrogen; the mass is equal to that of the proton and electron combined and they are unstable when isolated from the nucleus, undergoing beta decay. Slow, thermal, epithermal, and fast neutrons refer to the energy levels with which the neutrons are ejected from heavier nuclei during their decay. [NIH] Neutrophil: A type of white blood cell. [NIH] Neutrophil Activation: The process in which the neutrophil is stimulated by diverse substances, resulting in degranulation and/or generation of reactive oxygen products, and
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culminating in the destruction of invading pathogens. The stimulatory substances, including opsonized particles, immune complexes, and chemotactic factors, bind to specific cellsurface receptors on the neutrophil. [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] Nitrogen Oxides: Inorganic oxides that contain nitrogen. [NIH] Nocardia: A genus of gram-positive, aerobic bacteria whose species are widely distributed and are abundant in soil. Some strains are pathogenic opportunists for man and animals. [NIH]
Norepinephrine: Precursor of epinephrine that is secreted by the adrenal medulla and is a widespread central and autonomic neurotransmitter. Norepinephrine is the principal transmitter of most postganglionic sympathetic fibers and of the diffuse projection system in the brain arising from the locus ceruleus. It is also found in plants and is used pharmacologically as a sympathomimetic. [NIH] Norfloxacin: Quinoline-derived synthetic antibacterial agent with a very broad spectrum of action. Oral administration yields highly bactericidal plasma, tissue, and urine levels. Norfloxacin inhibits bacterial DNA-gyrase and is used in gastrointestinal, eye, and urinary infections. [NIH] Nosocomial: Pertaining to or originating in the hospital, said of an infection not present or incubating prior to admittance to the hospital, but generally occurring 72 hours after admittance; the term is usually used to refer to patient disease, but hospital personnel may also acquire nosocomial infection. [EU] Nuclear: A test of the structure, blood flow, and function of the kidneys. The doctor injects a mildly radioactive solution into an arm vein and uses x-rays to monitor its progress through the kidneys. [NIH] Nuclei: A body of specialized protoplasm found in nearly all cells and containing the chromosomes. [NIH] Nucleic acid: Either of two types of macromolecule (DNA or RNA) formed by polymerization of nucleotides. Nucleic acids are found in all living cells and contain the information (genetic code) for the transfer of genetic information from one generation to the next. [NIH] Nucleic Acid Hybridization: The process whereby two single-stranded polynucleotides form a double-stranded molecule, with hydrogen bonding between the complementary bases in the two strains. [NIH] 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] Observational study: An epidemiologic study that does not involve any intervention,
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experimental or otherwise. Such a study may be one in which nature is allowed to take its course, with changes in one characteristic being studied in relation to changes in other characteristics. Analytical epidemiologic methods, such as case-control and cohort study designs, are properly called observational epidemiology because the investigator is observing without intervention other than to record, classify, count, and statistically analyze results. [NIH] Ocular: 1. Of, pertaining to, or affecting the eye. 2. Eyepiece. [EU] Oesophagitis: Inflammation of the esophagus. [EU] Ofloxacin: An orally administered broad-spectrum quinolone antibacterial drug active against most gram-negative and gram-positive bacteria. [NIH] Oligomenorrhea: Abnormally infrequent menstruation. [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] 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] Oncologist: A doctor who specializes in treating cancer. Some oncologists specialize in a particular type of cancer treatment. For example, a radiation oncologist specializes in treating cancer with radiation. [NIH] Ondansetron: A competitive serotonin type 3 receptor antagonist. It is effective in the treatment of nausea and vomiting caused by cytotoxic chemotherapy drugs, including cisplatin, and it has reported anxiolytic and neuroleptic properties. [NIH] Opacity: Degree of density (area most dense taken for reading). [NIH] Ophthalmic: Pertaining to the eye. [EU] Opiate: A remedy containing or derived from opium; also any drug that induces sleep. [EU] Opium: The air-dried exudate from the unripe seed capsule of the opium poppy, Papaver somniferum, or its variant, P. album. It contains a number of alkaloids, but only a few morphine, codeine, and papaverine - have clinical significance. Opium has been used as an analgesic, antitussive, antidiarrheal, and antispasmodic. [NIH] Opportunistic Infections: An infection caused by an organism which becomes pathogenic under certain conditions, e.g., during immunosuppression. [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]
Organ Culture: The growth in aseptic culture of plant organs such as roots or shoots, beginning with organ primordia or segments and maintaining the characteristics of the organ. [NIH] Organ Transplantation: Transference of an organ between individuals of the same species or between individuals of different species. [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]
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Osmosis: Tendency of fluids (e.g., water) to move from the less concentrated to the more concentrated side of a semipermeable membrane. [NIH] Osmotic: Pertaining to or of the nature of osmosis (= the passage of pure solvent from a solution of lesser to one of greater solute concentration when the two solutions are separated by a membrane which selectively prevents the passage of solute molecules, but is permeable to the solvent). [EU] Osteoarthritis: A progressive, degenerative joint disease, the most common form of arthritis, especially in older persons. The disease is thought to result not from the aging process but from biochemical changes and biomechanical stresses affecting articular cartilage. In the foreign literature it is often called osteoarthrosis deformans. [NIH] Osteoblasts: Bone-forming cells which secrete an extracellular matrix. Hydroxyapatite crystals are then deposited into the matrix to form bone. [NIH] Osteocalcin: Vitamin K-dependent calcium-binding protein synthesized by osteoblasts and found primarily in bone. Serum osteocalcin measurements provide a noninvasive specific marker of bone metabolism. The protein contains three residues of the amino acid gammacarboxyglutamic acid (GLA), which, in the presence of calcium, promotes binding to hydroxyapatite and subsequent accumulation in bone matrix. [NIH] Osteoclasts: A large multinuclear cell associated with the absorption and removal of bone. An odontoclast, also called cementoclast, is cytomorphologically the same as an osteoclast and is involved in cementum resorption. [NIH] Osteogenic sarcoma: A malignant tumor of the bone. Also called osteosarcoma. [NIH] Osteomyelitis: Inflammation of bone caused by a pyogenic organism. It may remain localized or may spread through the bone to involve the marrow, cortex, cancellous tissue, and periosteum. [EU] Osteosarcoma: A cancer of the bone that affects primarily children and adolescents. Also called osteogenic sarcoma. [NIH] Otitis: Inflammation of the ear, which may be marked by pain, fever, abnormalities of hearing, hearing loss, tinnitus, and vertigo. [EU] Otitis Media: Inflammation of the middle ear. [NIH] Otorrhea: A discharge from the ear, especially a purulent one. [EU] Ovarian Follicle: Spheroidal cell aggregation in the ovary containing an ovum. It consists of an external fibro-vascular coat, an internal coat of nucleated cells, and a transparent, albuminous fluid in which the ovum is suspended. [NIH] Ovaries: The pair of female reproductive glands in which the ova, or eggs, are formed. The ovaries are located in the pelvis, one on each side of the uterus. [NIH] Ovary: Either of the paired glands in the female that produce the female germ cells and secrete some of the female sex hormones. [NIH] Overweight: An excess of body weight but not necessarily body fat; a body mass index of 25 to 29.9 kg/m2. [NIH] Ovulation: The discharge of a secondary oocyte from a ruptured graafian follicle. [NIH] Ovum: A female germ cell extruded from the ovary at ovulation. [NIH] Ovum Implantation: Endometrial implantation of the blastocyst. [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
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molecule. Univalent o. indicates loss of one electron; divalent o., the loss of two electrons. [EU]
Oxidative metabolism: A chemical process in which oxygen is used to make energy from carbohydrates (sugars). Also known as aerobic respiration, cell respiration, or aerobic metabolism. [NIH] Oxidative Stress: A disturbance in the prooxidant-antioxidant balance in favor of the former, leading to potential damage. Indicators of oxidative stress include damaged DNA bases, protein oxidation products, and lipid peroxidation products (Sies, Oxidative Stress, 1991, pxv-xvi). [NIH] Oxides: Binary compounds of oxygen containing the anion O(2-). The anion combines with metals to form alkaline oxides and non-metals to form acidic oxides. [NIH] Oxygen Consumption: The oxygen consumption is determined by calculating the difference between the amount of oxygen inhaled and exhaled. [NIH] Oxygenator: An apparatus by which oxygen is introduced into the blood during circulation outside the body, as during open heart surgery. [NIH] Oxytocic: 1. Pertaining to, characterized by, or promoting oxytocia (= rapid labor). 2. An agent that hastens evacuation of the uterus by stimulating contractions of the myometrium. [EU]
Pachymeningitis: Inflammation of the dura mater of the brain, the spinal cord or the optic nerve. [NIH] Paclitaxel: Antineoplastic agent isolated from the bark of the Pacific yew tree, Taxus brevifolia. Paclitaxel stabilizes microtubules in their polymerized form and thus mimics the action of the proto-oncogene proteins c-mos. [NIH] Paediatric: Of or relating to the care and medical treatment of children; belonging to or concerned with paediatrics. [EU] Pain Threshold: Amount of stimulation required before the sensation of pain is experienced. [NIH]
Palliative: 1. Affording relief, but not cure. 2. An alleviating medicine. [EU] Palsy: Disease of the peripheral nervous system occurring usually after many years of increased lead absorption. [NIH] Pancreas: A mixed exocrine and endocrine gland situated transversely across the posterior abdominal wall in the epigastric and hypochondriac regions. The endocrine portion is comprised of the Islets of Langerhans, while the exocrine portion is a compound acinar gland that secretes digestive enzymes. [NIH] Pancreatic: Having to do with the pancreas. [NIH] Pancreatic cancer: Cancer of the pancreas, a salivary gland of the abdomen. [NIH] Paneth Cells: Epithelial cells found in the basal part of the intestinal glands (crypts of Lieberkuhn). Paneth cells synthesize and secrete lysozyme and cryptdins. [NIH] Panic: A state of extreme acute, intense anxiety and unreasoning fear accompanied by disorganization of personality function. [NIH] Panic Disorder: A type of anxiety disorder characterized by unexpected panic attacks that last minutes or, rarely, hours. Panic attacks begin with intense apprehension, fear or terror and, often, a feeling of impending doom. Symptoms experienced during a panic attack include dyspnea or sensations of being smothered; dizziness, loss of balance or faintness; choking sensations; palpitations or accelerated heart rate; shakiness; sweating; nausea or other form of abdominal distress; depersonalization or derealization; paresthesias; hot
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flashes or chills; chest discomfort or pain; fear of dying and fear of not being in control of oneself or going crazy. Agoraphobia may also develop. Similar to other anxiety disorders, it may be inherited as an autosomal dominant trait. [NIH] Papillomavirus: A genus of Papovaviridae causing proliferation of the epithelium, which may lead to malignancy. A wide range of animals are infected including humans, chimpanzees, cattle, rabbits, dogs, and horses. [NIH] Paradoxical: Occurring at variance with the normal rule. [EU] Paralysis: Loss of ability to move all or part of the body. [NIH] Paraparesis: Mild to moderate loss of bilateral lower extremity motor function, which may be a manifestation of spinal cord diseases; peripheral nervous system diseases; muscular diseases; intracranial hypertension; parasagittal brain lesions; and other conditions. [NIH] 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] Parasympathomimetic: 1. Producing effects resembling those of stimulation of the parasympathetic nerve supply to a part. 2. An agent that produces effects similar to those produced by stimulation of the parasympathetic nerves. Called also cholinergic. [EU] Parathyroid: 1. Situated beside the thyroid gland. 2. One of the parathyroid glands. 3. A sterile preparation of the water-soluble principle(s) of the parathyroid glands, ad-ministered parenterally as an antihypocalcaemic, especially in the treatment of acute hypoparathyroidism with tetany. [EU] Parathyroid hormone: A substance made by the parathyroid gland that helps the body store and use calcium. Also called parathormone, parathyrin, or PTH. [NIH] Paresis: A general term referring to a mild to moderate degree of muscular weakness, occasionally used as a synonym for paralysis (severe or complete loss of motor function). In the older literature, paresis often referred specifically to paretic neurosyphilis. "General paresis" and "general paralysis" may still carry that connotation. Bilateral lower extremity paresis is referred to as paraparesis. [NIH] Paromomycin: An oligosaccharide antibiotic produced by various Streptomyces. [NIH] Paroxysmal: Recurring in paroxysms (= spasms or seizures). [EU] Partial remission: The shrinking, but not complete disappearance, of a tumor in response to therapy. Also called partial response. [NIH] Partial response: A decrease in the size of a tumor, or in the extent of cancer in the body, in response to treatment. [NIH] 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
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tissues and organs. [NIH] Pathophysiology: Altered functions in an individual or an organ due to disease. [NIH] Patient Selection: Criteria and standards used for the determination of the appropriateness of the inclusion of patients with specific conditions in proposed treatment plans and the criteria used for the inclusion of subjects in various clinical trials and other research protocols. [NIH] Pelvic: Pertaining to the pelvis. [EU] Pelvis: The lower part of the abdomen, located between the hip bones. [NIH] Pemphigus: Group of chronic blistering diseases characterized histologically by acantholysis and blister formation within the epidermis. [NIH] Penicillin: An antibiotic drug used to treat infection. [NIH] Pentoxifylline: A methylxanthine derivative that inhibits phosphodiesterase and affects blood rheology. It improves blood flow by increasing erythrocyte and leukocyte flexibility. It also inhibits platelet aggregation. Pentoxifylline modulates immunologic activity by stimulating cytokine production. [NIH] Pepsin: An enzyme made in the stomach that breaks down proteins. [NIH] Pepsin A: Formed from pig pepsinogen by cleavage of one peptide bond. The enzyme is a single polypeptide chain and is inhibited by methyl 2-diaazoacetamidohexanoate. It cleaves peptides preferentially at the carbonyl linkages of phenylalanine or leucine and acts as the principal digestive enzyme of gastric juice. [NIH] Peptic: Pertaining to pepsin or to digestion; related to the action of gastric juices. [EU] Peptic Ulcer: Ulcer that occurs in those portions of the alimentary tract which come into contact with gastric juice containing pepsin and acid. It occurs when the amount of acid and pepsin is sufficient to overcome the gastric mucosal barrier. [NIH] Peptide: Any compound consisting of two or more amino acids, the building blocks of proteins. Peptides are combined to make proteins. [NIH] Peptide Chain Elongation: The process whereby an amino acid is joined through a substituted amide linkage to a chain of peptides. [NIH] Peptide Fragments: Partial proteins formed by partial hydrolysis of complete proteins. [NIH] 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] Perforation: 1. The act of boring or piercing through a part. 2. A hole made through a part or substance. [EU] Perfusion: Bathing an organ or tissue with a fluid. In regional perfusion, a specific area of the body (usually an arm or a leg) receives high doses of anticancer drugs through a blood vessel. Such a procedure is performed to treat cancer that has not spread. [NIH] Pericardium: The fibroserous sac surrounding the heart and the roots of the great vessels. [NIH]
Perinatal: Pertaining to or occurring in the period shortly before and after birth; variously defined as beginning with completion of the twentieth to twenty-eighth week of gestation and ending 7 to 28 days after birth. [EU] Perineal: Pertaining to the perineum. [EU]
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Perineum: The area between the anus and the sex organs. [NIH] Periodontal disease: Disease involving the supporting structures of the teeth (as the gums and periodontal membranes). [NIH] Periodontal disease: Disease involving the supporting structures of the teeth (as the gums and periodontal membranes). [NIH] 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] Peristalsis: The rippling motion of muscles in the intestine or other tubular organs characterized by the alternate contraction and relaxation of the muscles that propel the contents onward. [NIH] Peritoneal: Having to do with the peritoneum (the tissue that lines the abdominal wall and covers most of the organs in the abdomen). [NIH] Peritoneal Cavity: The space enclosed by the peritoneum. It is divided into two portions, the greater sac and the lesser sac or omental bursa, which lies behind the stomach. The two sacs are connected by the foramen of Winslow, or epiploic foramen. [NIH] Peritoneum: Endothelial lining of the abdominal cavity, the parietal peritoneum covering the inside of the abdominal wall and the visceral peritoneum covering the bowel, the mesentery, and certain of the organs. The portion that covers the bowel becomes the serosal layer of the bowel wall. [NIH] Perivascular: Situated around a vessel. [EU] Peroxisome Proliferators: A class of nongenotoxic carcinogens that induce the production of hepatic peroxisomes and induce hepatic neoplasms after long-term administration. [NIH] Personality Disorders: A major deviation from normal patterns of behavior. [NIH] Petrolatum: A colloidal system of semisolid hydrocarbons obtained from petroleum. It is used as an ointment base, topical protectant, and lubricant. [NIH] Phagocyte: An immune system cell that can surround and kill microorganisms and remove dead cells. Phagocytes include macrophages. [NIH] Phagocytosis: The engulfing of microorganisms, other cells, and foreign particles by phagocytic cells. [NIH] 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] Pharmacodynamics: The study of the biochemical and physiological effects of drugs and the mechanisms of their actions, including the correlation of actions and effects of drugs with their chemical structure; also, such effects on the actions of a particular drug or drugs. [EU] Pharmacokinetic: The mathematical analysis of the time courses of absorption, distribution, and elimination of drugs. [NIH] Pharmacologic: Pertaining to pharmacology or to the properties and reactions of drugs. [EU] Pharyngitis: Inflammation of the throat. [NIH] Pharynx: The hollow tube about 5 inches long that starts behind the nose and ends at the top
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of the trachea (windpipe) and esophagus (the tube that goes to the stomach). [NIH] Phenolphthalein: An acid-base indicator which is colorless in acid solution, but turns pink to red as the solution becomes alkaline. It is used medicinally as a cathartic. [NIH] Phenotype: The outward appearance of the individual. It is the product of interactions between genes and between the genotype and the environment. This includes the killer phenotype, characteristic of yeasts. [NIH] Phenylalanine: An aromatic amino acid that is essential in the animal diet. It is a precursor of melanin, dopamine, noradrenalin, and thyroxine. [NIH] Phenylethyl Alcohol: An antimicrobial, antiseptic, and disinfectant that is used also as an aromatic essence and preservative in pharmaceutics and perfumery. [NIH] Phenytoin: An anticonvulsant that is used in a wide variety of seizures. It is also an antiarrhythmic and a muscle relaxant. The mechanism of therapeutic action is not clear, although several cellular actions have been described including effects on ion channels, active transport, and general membrane stabilization. The mechanism of its muscle relaxant effect appears to involve a reduction in the sensitivity of muscle spindles to stretch. Phenytoin has been proposed for several other therapeutic uses, but its use has been limited by its many adverse effects and interactions with other drugs. [NIH] Phonophoresis: Use of ultrasound to increase the percutaneous adsorption of drugs. [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] Phosphorylate: Attached to a phosphate group. [NIH] Phosphorylated: Attached to a phosphate group. [NIH] Phosphorylation: The introduction of a phosphoryl group into a compound through the formation of an ester bond between the compound and a phosphorus moiety. [NIH] Photocoagulation: Using a special strong beam of light (laser) to seal off bleeding blood vessels such as in the eye. The laser can also burn away blood vessels that should not have grown in the eye. This is the main treatment for diabetic retinopathy. [NIH] Physical Examination: Systematic and thorough inspection of the patient for physical signs of disease or abnormality. [NIH] Physiologic: Having to do with the functions of the body. When used in the phrase "physiologic age," it refers to an age assigned by general health, as opposed to calendar age. [NIH]
Physiology: The science that deals with the life processes and functions of organismus, their
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cells, tissues, and organs. [NIH] Pigmentation: Coloration or discoloration of a part by a pigment. [NIH] Pilocarpine: A slowly hydrolyzed muscarinic agonist with no nicotinic effects. Pilocarpine is used as a miotic and in the treatment of glaucoma. [NIH] Pilot study: The initial study examining a new method or treatment. [NIH] Piroxicam: 4-Hydroxy-2-methyl-N-2-pyridyl-2H-1,2-benzothiazine-3-carboxamide 1,1dioxide. A non-steroidal anti-inflammatory agent that is well established in the treatment of rheumatoid arthritis and osteoarthritis. Its usefulness has also been demonstrated in the treatment of musculoskeletal disorders, dysmenorrhea, and postoperative pain. Its long half-life enables it to be administered once daily. The drug has also been shown to be effective if administered rectally. Gastrointestinal complaints are the most frequently reported side effects. [NIH] Pituitary Gland: A small, unpaired gland situated in the sella turcica tissue. It is connected to the hypothalamus by a short stalk. [NIH] Placenta: A highly vascular fetal organ through which the fetus absorbs oxygen and other nutrients and excretes carbon dioxide and other wastes. It begins to form about the eighth day of gestation when the blastocyst adheres to the decidua. [NIH] Plant Components: The anatomical components of a plant, including seeds. [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; 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
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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-Derived Growth Factor: Mitogenic peptide growth hormone carried in the alphagranules of platelets. It is released when platelets adhere to traumatized tissues. Connective tissue cells near the traumatized region respond by initiating the process of replication. [NIH] Platelets: A type of blood cell that helps prevent bleeding by causing blood clots to form. Also called thrombocytes. [NIH] 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]
Pneumonia: Inflammation of the lungs. [NIH] Podophyllotoxin: The main active constituent of the resin from the roots of may apple or mandrake (Podophyllum peltatum and P. emodi). It is a potent spindle poison, toxic if taken internally, and has been used as a cathartic. It is very irritating to skin and mucous membranes, has keratolytic actions, has been used to treat warts and keratoses, and may have antineoplastic properties, as do some of its congeners and derivatives. [NIH] Poisoning: A condition or physical state produced by the ingestion, injection or inhalation of, or exposure to a deleterious agent. [NIH] Polyarthritis: An inflammation of several joints together. [EU] Polycystic: An inherited disorder characterized by many grape-like clusters of fluid-filled cysts that make both kidneys larger over time. These cysts take over and destroy working kidney tissue. PKD may cause chronic renal failure and end-stage renal disease. [NIH] Polycystic Ovary Syndrome: Clinical symptom complex characterized by oligomenorrhea or amenorrhea, anovulation, and regularly associated with bilateral polycystic ovaries. [NIH] Polyethylene: A vinyl polymer made from ethylene. It can be branched or linear. Branched or low-density polyethylene is tough and pliable but not to the same degree as linear polyethylene. Linear or high-density polyethylene has a greater hardness and tensile strength. Polyethylene is used in a variety of products, including implants and prostheses. [NIH]
Polyethylene Glycols: Alpha-Hydro-omega-hydroxypoly(oxy-1,2-ethanediyls). Additional polymers of ethylene oxide and water and their ethers. They vary in consistency from liquid to solid, depending on the molecular weight, indicated by a number following the name. Used as surfactants in industry, including foods, cosmetics and pharmaceutics; in biomedicine, as dispersing agents, solvents, ointment and suppository bases, vehicles, tablet excipients. Some specific groups are lauromagrogols, nonoxynols, octoxynols and poloxamers. [NIH]
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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] Polymorphism: The occurrence together of two or more distinct forms in the same population. [NIH] Polymyxin: Basic polypeptide antibiotic group obtained from Bacillus polymyxa. They affect the cell membrane by detergent action and may cause neuromuscular and kidney damage. At least eleven different members of the polymyxin group have been identified, each designated by a letter. [NIH] Polymyxin B: A mixture of polymyxins B1 and B2, obtained from Bacillus polymyxa strains. They are basic polypeptides of about eight amino acids and have cationic detergent action on cell membranes. Polymyxin B is used for infections with gram-negative organisms, but may be neurotoxic and nephrotoxic. [NIH] Polyposis: The development of numerous polyps (growths that protrude from a mucous membrane). [NIH] Polysaccharide: A type of carbohydrate. It contains sugar molecules that are linked together chemically. [NIH] Polyunsaturated fat: An unsaturated fat found in greatest amounts in foods derived from plants, including safflower, sunflower, corn, and soybean oils. [NIH] Pons: The part of the central nervous system lying between the medulla oblongata and the mesencephalon, ventral to the cerebellum, and consisting of a pars dorsalis and a pars ventralis. [NIH] 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] Postnatal: Occurring after birth, with reference to the newborn. [EU] Postoperative: After surgery. [NIH] Postoperative Nausea and Vomiting: Emesis and queasiness occurring after anesthesia. [NIH]
Postsynaptic: Nerve potential generated by an inhibitory hyperpolarizing stimulation. [NIH] Post-translational: The cleavage of signal sequence that directs the passage of the protein through a cell or organelle membrane. [NIH] Post-traumatic: Occurring as a result of or after injury. [EU] Post-traumatic stress disorder: A psychological disorder that develops in some individuals after a major traumatic experience such as war, rape, domestic violence, or accident. [NIH] Potassium: An element that is in the alkali group of metals. It has an atomic symbol K, atomic number 19, and atomic weight 39.10. It is the chief cation in the intracellular fluid of muscle and other cells. Potassium ion is a strong electrolyte and it plays a significant role in the regulation of fluid volume and maintenance of the water-electrolyte balance. [NIH] Potentiates: A degree of synergism which causes the exposure of the organism to a harmful substance to worsen a disease already contracted. [NIH] Potentiation: An overall effect of two drugs taken together which is greater than the sum of the effects of each drug taken alone. [NIH] Practice Guidelines: Directions or principles presenting current or future rules of policy for the health care practitioner to assist him in patient care decisions regarding diagnosis, therapy, or related clinical circumstances. The guidelines may be developed by government agencies at any level, institutions, professional societies, governing boards, or by the
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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] Prednisolone: A glucocorticoid with the general properties of the corticosteroids. It is the drug of choice for all conditions in which routine systemic corticosteroid therapy is indicated, except adrenal deficiency states. [NIH] Prednisone: A synthetic anti-inflammatory glucocorticoid derived from cortisone. It is biologically inert and converted to prednisolone in the liver. [NIH] Pregnancy Tests: Tests to determine whether or not an individual is pregnant. [NIH] Preleukemia: Conditions in which the abnormalities in the peripheral blood or bone marrow represent the early manifestations of acute leukemia, but in which the changes are not of sufficient magnitude or specificity to permit a diagnosis of acute leukemia by the usual clinical criteria. [NIH] Premedication: Preliminary administration of a drug preceding a diagnostic, therapeutic, or surgical procedure. The commonest types of premedication are antibiotics (antibiotic prophylaxis) and anti-anxiety agents. It does not include preanesthetic medication. [NIH] Prenatal: Existing or occurring before birth, with reference to the fetus. [EU] Presynaptic: Situated proximal to a synapse, or occurring before the synapse is crossed. [EU] Prevalence: The total number of cases of a given disease in a specified population at a designated time. It is differentiated from incidence, which refers to the number of new cases in the population at a given time. [NIH] Prickle: Several layers of the epidermis where the individual cells are connected by cell bridges. [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] Procarbazine: An antineoplastic agent used primarily in combination with mechlorethamine, vincristine, and prednisone (the MOPP protocol) in the treatment of Hodgkin's disease. [NIH] Procollagen: A biosynthetic precursor of collagen containing additional amino acid sequences at the amino-terminal ends of the three polypeptide chains. Protocollagen, a precursor of procollagen consists of procollagen peptide chains in which proline and lysine have not yet been hydroxylated. [NIH] Progeny: The offspring produced in any generation. [NIH] Progesterone: Pregn-4-ene-3,20-dione. The principal progestational hormone of the body, secreted by the corpus luteum, adrenal cortex, and placenta. Its chief function is to prepare the uterus for the reception and development of the fertilized ovum. It acts as an antiovulatory agent when administered on days 5-25 of the menstrual cycle. [NIH] Progression: Increase in the size of a tumor or spread of cancer in the body. [NIH]
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Progressive: Advancing; going forward; going from bad to worse; increasing in scope or severity. [EU] Progressive disease: Cancer that is increasing in scope or severity. [NIH] Projection: A defense mechanism, operating unconsciously, whereby that which is emotionally unacceptable in the self is rejected and attributed (projected) to others. [NIH] Prolactin: Pituitary lactogenic hormone. A polypeptide hormone with a molecular weight of about 23,000. It is essential in the induction of lactation in mammals at parturition and is synergistic with estrogen. The hormone also brings about the release of progesterone from lutein cells, which renders the uterine mucosa suited for the embedding of the ovum should fertilization occur. [NIH] Proline: A non-essential amino acid that is synthesized from glutamic acid. It is an essential component of collagen and is important for proper functioning of joints and tendons. [NIH] Promoter: A chemical substance that increases the activity of a carcinogenic process. [NIH] Promotor: In an operon, a nucleotide sequence located at the operator end which contains all the signals for the correct initiation of genetic transcription by the RNA polymerase holoenzyme and determines the maximal rate of RNA synthesis. [NIH] Prone: Having the front portion of the body downwards. [NIH] Prophylaxis: An attempt to prevent disease. [NIH] 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] Prostaglandin: Any of a group of components derived from unsaturated 20-carbon fatty acids, primarily arachidonic acid, via the cyclooxygenase pathway that are extremely potent mediators of a diverse group of physiologic processes. The abbreviation for prostaglandin is PG; specific compounds are designated by adding one of the letters A through I to indicate the type of substituents found on the hydrocarbon skeleton and a subscript (1, 2 or 3) to indicate the number of double bonds in the hydrocarbon skeleton e.g., PGE2. The predominant naturally occurring prostaglandins all have two double bonds and are synthesized from arachidonic acid (5,8,11,14-eicosatetraenoic acid) by the pathway shown in the illustration. The 1 series and 3 series are produced by the same pathway with fatty acids having one fewer double bond (8,11,14-eicosatrienoic acid or one more double bond (5,8,11,14,17-eicosapentaenoic acid) than arachidonic acid. The subscript a or ß indicates the configuration at C-9 (a denotes a substituent below the plane of the ring, ß, above the plane). The naturally occurring PGF's have the a configuration, e.g., PGF2a. All of the prostaglandins act by binding to specific cell-surface receptors causing an increase in the level of the intracellular second messenger cyclic AMP (and in some cases cyclic GMP also). The effect produced by the cyclic AMP increase depends on the specific cell type. In some cases there is also a positive feedback effect. Increased cyclic AMP increases prostaglandin synthesis leading to further increases in cyclic AMP. [EU] Prostaglandins A: (13E,15S)-15-Hydroxy-9-oxoprosta-10,13-dien-1-oic acid (PGA(1)); (5Z,13E,15S)-15-hydroxy-9-oxoprosta-5,10,13-trien-1-oic acid (PGA(2)); (5Z,13E,15S,17Z)-15hydroxy-9-oxoprosta-5,10,13,17-tetraen-1-oic acid (PGA(3)). A group of naturally occurring secondary prostaglandins derived from PGE. PGA(1) and PGA(2) as well as their 19hydroxy derivatives are found in many organs and tissues. [NIH] Prostaglandins D: Physiologically active prostaglandins found in many tissues and organs. They show pressor activity, are mediators of inflammation, and have potential antithrombotic effects. [NIH]
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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] Protein Kinases: A family of enzymes that catalyze the conversion of ATP and a protein to ADP and a phosphoprotein. EC 2.7.1.37. [NIH] Protein S: The vitamin K-dependent cofactor of activated protein C. Together with protein C, it inhibits the action of factors VIIIa and Va. A deficiency in protein S can lead to recurrent venous and arterial thrombosis. [NIH] Proteins: Polymers of amino acids linked by peptide bonds. The specific sequence of amino acids determines the shape and function of the protein. [NIH] Protein-Tyrosine Kinase: An enzyme that catalyzes the phosphorylation of tyrosine residues in proteins with ATP or other nucleotides as phosphate donors. EC 2.7.1.112. [NIH] 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] Protocol: The detailed plan for a clinical trial that states the trial's rationale, purpose, drug or vaccine dosages, length of study, routes of administration, who may participate, and other aspects of trial design. [NIH] Protons: Stable elementary particles having the smallest known positive charge, found in the nuclei of all elements. The proton mass is less than that of a neutron. A proton is the nucleus of the light hydrogen atom, i.e., the hydrogen ion. [NIH] Proto-Oncogene Proteins: Products of proto-oncogenes. Normally they do not have oncogenic or transforming properties, but are involved in the regulation or differentiation of cell growth. They often have protein kinase activity. [NIH] Proto-Oncogene Proteins c-mos: Cellular proteins encoded by the c-mos genes. They function in the cell cycle to maintain maturation promoting factor in the active state and have protein-serine/threonine kinase activity. Oncogenic transformation can take place when c-mos proteins are expressed at the wrong time. [NIH] Protozoa: A subkingdom consisting of unicellular organisms that are the simplest in the animal kingdom. Most are free living. They range in size from submicroscopic to macroscopic. Protozoa are divided into seven phyla: Sarcomastigophora, Labyrinthomorpha, Apicomplexa, Microspora, Ascetospora, Myxozoa, and Ciliophora. [NIH] Protozoan: 1. Any individual of the protozoa; protozoon. 2. Of or pertaining to the protozoa; protozoal. [EU] Proviruses: Duplex DNA sequences in eukaryotic chromosomes, corresponding to the genome of a virus, that are transmitted from one cell generation to the next without causing
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lysis of the host. Proviruses are often associated with neoplastic cell transformation and are key features of retrovirus biology. [NIH] Proximal: Nearest; closer to any point of reference; opposed to distal. [EU] Pruritic: Pertaining to or characterized by pruritus. [EU] Pruritus: An intense itching sensation that produces the urge to rub or scratch the skin to obtain relief. [NIH] Psychiatric: Pertaining to or within the purview of psychiatry. [EU] Psychiatry: The medical science that deals with the origin, diagnosis, prevention, and treatment of mental disorders. [NIH] Psychic: Pertaining to the psyche or to the mind; mental. [EU] Psychoactive: Those drugs which alter sensation, mood, consciousness or other psychological or behavioral functions. [NIH] Psychology: The science dealing with the study of mental processes and behavior in man and animals. [NIH] Psychomotor: Pertaining to motor effects of cerebral or psychic activity. [EU] Puberty: The period during which the secondary sex characteristics begin to develop and 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] 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] Pulmonary Sarcoidosis: A disease of unknown etiology characterized by tuberclelike, granulomatous nodules which may affect the skin, the lungs, the lymph nodes, the bones of the distal extremities, the conjunctiva, the lacrimal gland, the retina and the uveal tract. [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] Pylorus: The opening in a vertebrate from the stomach into the intestine. [EU] Pyogenic: Producing pus; pyopoietic (= liquid inflammation product made up of cells and a
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thin fluid called liquor puris). [EU] Pyrimidines: A family of 6-membered heterocyclic compounds occurring in nature in a wide variety of forms. They include several nucleic acid constituents (cytosine, thymine, and uracil) and form the basic structure of the barbiturates. [NIH] Quality of Life: A generic concept reflecting concern with the modification and enhancement of life attributes, e.g., physical, political, moral and social environment. [NIH] Quaternary: 1. Fourth in order. 2. Containing four elements or groups. [EU] Quiescent: Marked by a state of inactivity or repose. [EU] Quipazine: A pharmacologic congener of serotonin that contracts smooth muscle and has actions similar to those of tricyclic antidepressants. It has been proposed as an oxytocic. [NIH] Rabies: A highly fatal viral infection of the nervous system which affects all warm-blooded animal species. It is one of the most important of the zoonoses because of the inevitably fatal outcome for the infected human. [NIH] Rabies Virus: The type species of lyssavirus causing rabies in humans and other animals. Transmission is mostly by animal bites through saliva. The virus is neurotropic multiplying in neurons and myotubes of vertebrates. [NIH] Race: A population within a species which exhibits general similarities within itself, but is both discontinuous and distinct from other populations of that species, though not sufficiently so as to achieve the status of a taxon. [NIH] Racemic: Optically inactive but resolvable in the way of all racemic compounds. [NIH] Radiation: Emission or propagation of electromagnetic energy (waves/rays), or the waves/rays themselves; a stream of electromagnetic particles (electrons, neutrons, protons, alpha particles) or a mixture of these. The most common source is the sun. [NIH] Radiation oncologist: A doctor who specializes in using radiation to treat cancer. [NIH] Radiation therapy: The use of high-energy radiation from x-rays, gamma rays, neutrons, and other sources to kill cancer cells and shrink tumors. Radiation may come from a machine outside the body (external-beam radiation therapy), or it may come from radioactive material placed in the body in the area near cancer cells (internal radiation therapy, implant radiation, or brachytherapy). Systemic radiation therapy uses a radioactive substance, such as a radiolabeled monoclonal antibody, that circulates throughout the body. Also called radiotherapy. [NIH] Radioactive: Giving off radiation. [NIH] Radiography: Examination of any part of the body for diagnostic purposes by means of roentgen rays, recording the image on a sensitized surface (such as photographic film). [NIH] Radioimmunotherapy: Radiotherapy where cytotoxic radionuclides are linked to antibodies in order to deliver toxins directly to tumor targets. Therapy with targeted radiation rather than antibody-targeted toxins (immunotoxins) has the advantage that adjacent tumor cells, which lack the appropriate antigenic determinants, can be destroyed by radiation cross-fire. Radioimmunotherapy is sometimes called targeted radiotherapy, but this latter term can also refer to radionuclides linked to non-immune molecules (radiotherapy). [NIH] 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
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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] Raltitrexed: An anticancer drug that inhibits tumor cells from multiplying by interfering with cells' ability to make DNA. Also called ICI D1694. [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] Rape: Unlawful sexual intercourse without consent of the victim. [NIH] Reactivation: The restoration of activity to something that has been inactivated. [EU] Reactive Oxygen Species: Reactive intermediate oxygen species including both radicals and non-radicals. These substances are constantly formed in the human body and have been shown to kill bacteria and inactivate proteins, and have been implicated in a number of diseases. Scientific data exist that link the reactive oxygen species produced by inflammatory phagocytes to cancer development. [NIH] Receptor: A molecule inside or on the surface of a cell that binds to a specific substance and causes a specific physiologic effect in the cell. [NIH] Receptors, Serotonin: Cell-surface proteins that bind serotonin and trigger intracellular changes which influence the behavior of cells. Several types of serotonin receptors have been recognized which differ in their pharmacology, molecular biology, and mode of action. [NIH] Recombinant: A cell or an individual with a new combination of genes not found together in either parent; usually applied to linked genes. [EU] Recombination: The formation of new combinations of genes as a result of segregation in crosses between genetically different parents; also the rearrangement of linked genes due to crossing-over. [NIH] Rectal: By or having to do with the rectum. The rectum is the last 8 to 10 inches of the large intestine and ends at the anus. [NIH] Rectum: The last 8 to 10 inches of the large intestine. [NIH] Recurrence: The return of a sign, symptom, or disease after a remission. [NIH] Red blood cells: RBCs. Cells that carry oxygen to all parts of the body. Also called erythrocytes. [NIH] Red Nucleus: A pinkish-yellow portion of the midbrain situated in the rostral mesencephalic tegmentum. It receives a large projection from the contralateral half of the cerebellum via the superior cerebellar peduncle and a projection from the ipsilateral motor cortex. [NIH] Reductase: Enzyme converting testosterone to dihydrotestosterone. [NIH] Refer: To send or direct for treatment, aid, information, de decision. [NIH] Reflex: An involuntary movement or exercise of function in a part, excited in response to a stimulus applied to the periphery and transmitted to the brain or spinal cord. [NIH] Reflux: The term used when liquid backs up into the esophagus from the stomach. [NIH] Refraction: A test to determine the best eyeglasses or contact lenses to correct a refractive error (myopia, hyperopia, or astigmatism). [NIH] Refractory: Not readily yielding to treatment. [EU] Regeneration: The natural renewal of a structure, as of a lost tissue or part. [EU] Regimen: A treatment plan that specifies the dosage, the schedule, and the duration of treatment. [NIH]
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Relapse: The return of signs and symptoms of cancer after a period of improvement. [NIH] Relaxin: Hormone produced by the ovaries during pregnancy that loosens ligaments that hold the hip bones together. [NIH] Remission: A decrease in or disappearance of signs and symptoms of cancer. In partial remission, some, but not all, signs and symptoms of cancer have disappeared. In complete remission, all signs and symptoms of cancer have disappeared, although there still may be cancer in the body. [NIH] Renal cell carcinoma: A type of kidney cancer. [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] Research Support: Financial support of research activities. [NIH] Resection: Removal of tissue or part or all of an organ by surgery. [NIH] Resorption: The loss of substance through physiologic or pathologic means, such as loss of dentin and cementum of a tooth, or of the alveolar process of the mandible or maxilla. [EU] Respiration: The act of breathing with the lungs, consisting of inspiration, or the taking into the lungs of the ambient air, and of expiration, or the expelling of the modified air which contains more carbon dioxide than the air taken in (Blakiston's Gould Medical Dictionary, 4th ed.). This does not include tissue respiration (= oxygen consumption) or cell respiration (= cell respiration). [NIH] Respiratory distress syndrome: A lung disease that occurs primarily in premature infants; the newborn must struggle for each breath and blueing of its skin reflects the baby's inability to get enough oxygen. [NIH] Respiratory Mechanics: The physical or mechanical action of the lungs, diaphragm, ribs, and chest wall during respiration. It includes airflow, lung volume, neural and reflex controls, mechanoreceptors, breathing patterns, etc. [NIH] Respiratory Physiology: Functions and activities of the respiratory tract as a whole or of any of its parts. [NIH] Respiratory syncytial virus: RSV. A virus that causes respiratory infections with cold-like symptoms. [NIH] Respiratory System: The tubular and cavernous organs and structures, by means of which pulmonary ventilation and gas exchange between ambient air and the blood are brought about. [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]
Response rate: The percentage of patients whose cancer shrinks or disappears after treatment. [NIH] Restitution: The restoration to a normal state. [NIH]
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Restoration: Broad term applied to any inlay, crown, bridge or complete denture which restores or replaces loss of teeth or oral tissues. [NIH] Retching: Dry vomiting. [NIH] Retina: The ten-layered nervous tissue membrane of the eye. It is continuous with the optic nerve and receives images of external objects and transmits visual impulses to the brain. Its outer surface is in contact with the choroid and the inner surface with the vitreous body. The outer-most layer is pigmented, whereas the inner nine layers are transparent. [NIH] Retinal: 1. Pertaining to the retina. 2. The aldehyde of retinol, derived by the oxidative enzymatic splitting of absorbed dietary carotene, and having vitamin A activity. In the retina, retinal combines with opsins to form visual pigments. One isomer, 11-cis retinal combines with opsin in the rods (scotopsin) to form rhodopsin, or visual purple. Another, all-trans retinal (trans-r.); visual yellow; xanthopsin) results from the bleaching of rhodopsin by light, in which the 11-cis form is converted to the all-trans form. Retinal also combines with opsins in the cones (photopsins) to form the three pigments responsible for colour vision. Called also retinal, and retinene1. [EU] Retinoblastoma: An eye cancer that most often occurs in children younger than 5 years. It occurs in hereditary and nonhereditary (sporadic) forms. [NIH] Retrograde: 1. Moving backward or against the usual direction of flow. 2. Degenerating, deteriorating, or catabolic. [EU] Retroperitoneal: Having to do with the area outside or behind the peritoneum (the tissue that lines the abdominal wall and covers most of the organs in the abdomen). [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] 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] Rheumatic Diseases: Disorders of connective tissue, especially the joints and related structures, characterized by inflammation, degeneration, or metabolic derangement. [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] Rhinovirus: A genus of Picornaviridae inhabiting primarily the respiratory tract of mammalian hosts. It includes the human strains associated with common colds. [NIH] Ribonucleic acid: RNA. One of the two nucleic acids found in all cells. The other is deoxyribonucleic acid (DNA). Ribonucleic acid transfers genetic information from DNA to proteins produced by the cell. [NIH] Ribonucleoproteins: Proteins conjugated with ribonucleic acids (RNA) or specific RNA. Many viruses are ribonucleoproteins. [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]
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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] Rituximab: A type of monoclonal antibody used in cancer detection or therapy. Monoclonal antibodies are laboratory-produced substances that can locate and bind to cancer cells. [NIH] Rod: A reception for vision, located in the retina. [NIH] Round Window: Fenestra of the cochlea; an opening in the medial wall of the middle ear leading into the cochlea. [NIH] Rubulavirus: A genus of the family Paramyxoviridae (subfamily Paramyxovirinae) where all the species have hemagglutinin and neuraminidase activities but lack a C protein. Mumps virus is the type species. [NIH] Saccule: The smaller of the 2 sacs within the vestibule of the ear. [NIH] Saccule and Utricle: Two membranous sacs within the vestibule of the inner ear. The smaller, the saccule, lies near the opening of the scala vestibuli. The larger, the utricle, is in the superoposterior part of the vestibule. Both receive filaments from the vestibulocochlear nerve. [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] Salvage Therapy: A therapeutic approach, involving chemotherapy, radiation therapy, or surgery, after initial regimens have failed to lead to improvement in a patient's condition. Salvage therapy is most often used for neoplastic diseases. [NIH] Saphenous: Applied to certain structures in the leg, e. g. nerve vein. [NIH] Saphenous Vein: The vein which drains the foot and leg. [NIH] Saponins: Sapogenin glycosides. A type of glycoside widely distributed in plants. Each consists of a sapogenin as the aglycon moiety, and a sugar. The sapogenin may be a steroid or a triterpene and the sugar may be glucose, galactose, a pentose, or a methylpentose. Sapogenins are poisonous towards the lower forms of life and are powerful hemolytics when injected into the blood stream able to dissolve red blood cells at even extreme dilutions. [NIH] Satellite: Applied to a vein which closely accompanies an artery for some distance; in cytogenetics, a chromosomal agent separated by a secondary constriction from the main body of the chromosome. [NIH] Schizoid: Having qualities resembling those found in greater degree in schizophrenics; a person of schizoid personality. [NIH] Schizophrenia: A mental disorder characterized by a special type of disintegration of the personality. [NIH] Schizotypal Personality Disorder: A personality disorder in which there are oddities of thought (magical thinking, paranoid ideation, suspiciousness), perception (illusions, depersonalization), speech (digressive, vague, overelaborate), and behavior (inappropriate affect in social interactions, frequently social isolation) that are not severe enough to characterize schizophrenia. [NIH]
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Sclerosis: A pathological process consisting of hardening or fibrosis of an anatomical structure, often a vessel or a nerve. [NIH] Scopolamine: An alkaloid from Solanaceae, especially Datura metel L. and Scopola carniolica. Scopolamine and its quaternary derivatives act as antimuscarinics like atropine, but may have more central nervous system effects. Among the many uses are as an anesthetic premedication, in urinary incontinence, in motion sickness, as an antispasmodic, and as a mydriatic and cycloplegic. [NIH] Screening: Checking for disease when there are no symptoms. [NIH] Sebaceous: Gland that secretes sebum. [NIH] Sebaceous gland: Gland that secretes sebum. [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] Sedative: 1. Allaying activity and excitement. 2. An agent that allays excitement. [EU] Sedimentation: The act of causing the deposit of sediment, especially by the use of a centrifugal machine. [EU] Seizures: Clinical or subclinical disturbances of cortical function due to a sudden, abnormal, excessive, and disorganized discharge of brain cells. Clinical manifestations include abnormal motor, sensory and psychic phenomena. Recurrent seizures are usually referred to as epilepsy or "seizure disorder." [NIH] 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] Selenium: An element with the atomic symbol Se, atomic number 34, and atomic weight 78.96. It is an essential micronutrient for mammals and other animals but is toxic in large amounts. Selenium protects intracellular structures against oxidative damage. It is an essential component of glutathione peroxidase. [NIH] 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] Sensibility: The ability to receive, feel and appreciate sensations and impressions; the quality of being sensitive; the extend to which a method gives results that are free from false negatives. [NIH] Septic: Produced by or due to decomposition by microorganisms; putrefactive. [EU] Sequencing: The determination of the order of nucleotides in a DNA or RNA chain. [NIH] Serine: A non-essential amino acid occurring in natural form as the L-isomer. It is synthesized from glycine or threonine. It is involved in the biosynthesis of purines, pyrimidines, and other amino acids. [NIH]
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Serotonin: A biochemical messenger and regulator, synthesized from the essential amino acid L-tryptophan. In humans it is found primarily in the central nervous system, gastrointestinal tract, and blood platelets. Serotonin mediates several important physiological functions including neurotransmission, gastrointestinal motility, hemostasis, and cardiovascular integrity. Multiple receptor families (receptors, serotonin) explain the broad physiological actions and distribution of this biochemical mediator. [NIH] Serrata: The serrated anterior border of the retina located approximately 8.5 mm from the limbus and adjacent to the pars plana of the ciliary body. [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] Sex Determination: The biological characteristics which distinguish human beings as female or male. [NIH] Sex Hormone-Binding Globulin: A glycoprotein migrating as a beta-globulin. Its molecular weight, 52,000 or 95,000-115,000, indicates that it exists as a dimer. The protein binds testosterone, dihydrotestosterone, and estradiol in the plasma. Sex hormone-binding protein has the same amino acid sequence as androgen-binding protein. They differ by their sites of synthesis and post-translational oligosacaccharide modifications. [NIH] Shock: The general bodily disturbance following a severe injury; an emotional or moral upset occasioned by some disturbing or unexpected experience; disruption of the circulation, which can upset all body functions: sometimes referred to as circulatory shock. [NIH]
Side effect: A consequence other than the one(s) for which an agent or measure is used, as the adverse effects produced by a drug, especially on a tissue or organ system other than the one sought to be benefited by its administration. [EU] Sigmoid: 1. Shaped like the letter S or the letter C. 2. The sigmoid colon. [EU] Sigmoid Colon: The lower part of the colon that empties into the rectum. [NIH] Signal Transduction: The intercellular or intracellular transfer of information (biological activation/inhibition) through a signal pathway. In each signal transduction system, an activation/inhibition signal from a biologically active molecule (hormone, neurotransmitter) is mediated via the coupling of a receptor/enzyme to a second messenger system or to an ion channel. Signal transduction plays an important role in activating cellular functions, cell differentiation, and cell proliferation. Examples of signal transduction systems are the GABA-postsynaptic receptor-calcium ion channel system, the receptor-mediated T-cell activation pathway, and the receptor-mediated activation of phospholipases. Those coupled to membrane depolarization or intracellular release of calcium include the receptormediated activation of cytotoxic functions in granulocytes and the synaptic potentiation of protein kinase activation. Some signal transduction pathways may be part of larger signal transduction pathways; for example, protein kinase activation is part of the platelet activation signal pathway. [NIH] Signs and Symptoms: Clinical manifestations that can be either objective when observed by a physician, or subjective when perceived by the patient. [NIH] Sirolimus: A macrolide compound obtained from Streptomyces hygroscopicus that acts by
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selectively blocking the transcriptional activation of cytokines thereby inhibiting cytokine production. It is bioactive only when bound to immunophilins. Sirolimus is a potent immunosuppressant and possesses both antifungal and antineoplastic properties. [NIH] Skeletal: Having to do with the skeleton (boney part of the body). [NIH] Skeleton: The framework that supports the soft tissues of vertebrate animals and protects many of their internal organs. The skeletons of vertebrates are made of bone and/or cartilage. [NIH] Skull: The skeleton of the head including the bones of the face and the bones enclosing the brain. [NIH] Small intestine: The part of the digestive tract that is located between the stomach and the large intestine. [NIH] Smoldering leukemia: Disease in which the bone marrow does not function normally. Also called preleukemia or myelodysplastic syndrome. [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] Social Isolation: The separation of individuals or groups resulting in the lack of or minimizing of social contact and/or communication. This separation may be accomplished by physical separation, by social barriers and by psychological mechanisms. In the latter, there may be interaction but no real communication. [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] Sodium Channels: Cell membrane glycoproteins selective for sodium ions. Fast sodium current is associated with the action potential in neural membranes. [NIH] Soft tissue: Refers to muscle, fat, fibrous tissue, blood vessels, or other supporting tissue of the body. [NIH] Soft tissue sarcoma: A sarcoma that begins in the 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] Somatostatin: A polypeptide hormone produced in the hypothalamus, and other tissues and organs. It inhibits the release of human growth hormone, and also modulates important physiological functions of the kidney, pancreas, and gastrointestinal tract. Somatostatin receptors are widely expressed throughout the body. Somatostatin also acts as a neurotransmitter in the central and peripheral nervous systems. [NIH]
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Somatotropin: A small peptide hormone released by the anterior pituitary under hypothalamic control. Somatotropin, or growth hormone, stimulates mitosis, cell growth, and, for some cell types, differentiation in many tissues of the body. It has profound effects on many aspects of gene expression and metabolism. [NIH] Sorbic Acid: Mold and yeast inhibitor. Used as a fungistatic agent for foods, especially cheeses. [NIH] Sound wave: An alteration of properties of an elastic medium, such as pressure, particle displacement, or density, that propagates through the medium, or a superposition of such alterations. [NIH] Soybean Oil: Oil from soybean or soybean plant. [NIH] 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] Spectrum: A charted band of wavelengths of electromagnetic vibrations obtained by refraction and diffraction. By extension, a measurable range of activity, such as the range of bacteria affected by an antibiotic (antibacterial s.) or the complete range of manifestations of a disease. [EU] Sperm: The fecundating fluid of the male. [NIH] Spinal cord: The main trunk or bundle of nerves running down the spine through holes in the spinal bone (the vertebrae) from the brain to the level of the lower back. [NIH] Spinal Nerves: The 31 paired peripheral nerves formed by the union of the dorsal and ventral spinal roots from each spinal cord segment. The spinal nerve plexuses and the spinal roots are also included. [NIH] Spinal tap: A procedure in which a needle is put into the lower part of the spinal column to collect cerebrospinal fluid or to give anticancer drugs intrathecally. Also called a lumbar puncture. [NIH] Spinous: Like a spine or thorn in shape; having spines. [NIH] Spleen: An organ that is part of the lymphatic system. The spleen produces lymphocytes, filters the blood, stores blood cells, and destroys old blood cells. It is located on the left side of the abdomen near the stomach. [NIH] Sporadic: Neither endemic nor epidemic; occurring occasionally in a random or isolated manner. [EU] Squamous: Scaly, or platelike. [EU] Squamous cell carcinoma: Cancer that begins in squamous cells, which are thin, flat cells resembling fish scales. Squamous cells are found in the tissue that forms the surface of the skin, the lining of the hollow organs of the body, and the passages of the respiratory and digestive tracts. Also called epidermoid carcinoma. [NIH] Squamous cell carcinoma: Cancer that begins in squamous cells, which are thin, flat cells
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resembling fish scales. Squamous cells are found in the tissue that forms the surface of the skin, the lining of the hollow organs of the body, and the passages of the respiratory and digestive tracts. Also called epidermoid carcinoma. [NIH] Squamous cells: Flat cells that look like fish scales under a microscope. These cells cover internal and external surfaces of the body. [NIH] Stabilization: The creation of a stable state. [EU] Stasis: A word termination indicating the maintenance of (or maintaining) a constant level; preventing increase or multiplication. [EU] Staurosporine: A drug that belongs to the family of drugs called alkaloids. It is being studied in the treatment of cancer. [NIH] Steel: A tough, malleable, iron-based alloy containing up to, but no more than, two percent carbon and often other metals. It is used in medicine and dentistry in implants and instrumentation. [NIH] Stellate: Star shaped. [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] Stenosis: Narrowing or stricture of a duct or canal. [EU] Stent: A device placed in a body structure (such as a blood vessel or the gastrointestinal tract) to provide support and keep the structure open. [NIH] Sterility: 1. The inability to produce offspring, i.e., the inability to conceive (female s.) or to induce conception (male s.). 2. The state of being aseptic, or free from microorganisms. [EU] Steroid: A group name for lipids that contain a hydrogenated cyclopentanoperhydrophenanthrene ring system. Some of the substances included in this group are progesterone, adrenocortical hormones, the gonadal hormones, cardiac aglycones, bile acids, sterols (such as cholesterol), toad poisons, saponins, and some of the carcinogenic hydrocarbons. [EU] Stimulant: 1. Producing stimulation; especially producing stimulation by causing tension on muscle fibre through the nervous tissue. 2. An agent or remedy that produces stimulation. [EU]
Stimulus: That which can elicit or evoke action (response) in a muscle, nerve, gland or other excitable issue, or cause an augmenting action upon any function or metabolic process. [NIH] Stomach: An organ of digestion situated in the left upper quadrant of the abdomen between the termination of the esophagus and the beginning of the duodenum. [NIH] Stool: The waste matter discharged in a bowel movement; feces. [NIH] Strabismus: Deviation of the eye which the patient cannot overcome. The visual axes assume a position relative to each other different from that required by the physiological conditions. The various forms of strabismus are spoken of as tropias, their direction being indicated by the appropriate prefix, as cyclo tropia, esotropia, exotropia, hypertropia, and hypotropia. Called also cast, heterotropia, manifest deviation, and squint. [EU] Streptococcal: Caused by infection due to any species of streptococcus. [NIH] Streptococcus: A genus of gram-positive, coccoid bacteria whose organisms occur in pairs or chains. No endospores are produced. Many species exist as commensals or parasites on
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man or animals with some being highly pathogenic. A few species are saprophytes and occur in the natural environment. [NIH] Stress: Forcibly exerted influence; pressure. Any condition or situation that causes strain or tension. Stress may be either physical or psychologic, or both. [NIH] Stricture: The abnormal narrowing of a body opening. Also called stenosis. [NIH] Stridor: The loud, harsh, vibrating sound produced by partial obstruction of the larynx or trachea. [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] 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] Supplementation: Adding nutrients to the diet. [NIH] Suppository: A medicated mass adapted for introduction into the rectal, vaginal, or urethral orifice of the body, suppository bases are solid at room temperature but melt or dissolve at body temperature. Commonly used bases are cocoa butter, glycerinated gelatin, hydrogenated vegetable oils, polyethylene glycols of various molecular weights, and fatty acid esters of polyethylene glycol. [EU] 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]
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Surfactant: A fat-containing protein in the respiratory passages which reduces the surface tension of pulmonary fluids and contributes to the elastic properties of pulmonary tissue. [NIH]
Suspensions: Colloids with liquid continuous phase and solid dispersed phase; the term is used loosely also for solid-in-gas (aerosol) and other colloidal systems; water-insoluble drugs may be given as suspensions. [NIH] Sweat: The fluid excreted by the sweat glands. It consists of water containing sodium chloride, phosphate, urea, ammonia, and other waste products. [NIH] Sweat Glands: Sweat-producing structures that are embedded in the dermis. Each gland consists of a single tube, a coiled body, and a superficial duct. [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] Synapse: The region where the processes of two neurons come into close contiguity, and the nervous impulse passes from one to the other; the fibers of the two are intermeshed, but, according to the general view, there is no direct contiguity. [NIH] 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] Synchrony: The normal physiologic sequencing of atrial and ventricular activation and contraction. [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] Systemic disease: Disease that affects the whole body. [NIH] Systemic lupus erythematosus: SLE. A chronic inflammatory connective tissue disease marked by skin rashes, joint pain and swelling, inflammation of the kidneys, inflammation of the fibrous tissue surrounding the heart (i.e., the pericardium), as well as other problems. Not all affected individuals display all of these problems. May be referred to as lupus. [NIH] Systolic: Indicating the maximum arterial pressure during contraction of the left ventricle of the heart. [EU] Tacrolimus: A macrolide isolated from the culture broth of a strain of Streptomyces tsukubaensis that has strong immunosuppressive activity in vivo and prevents the activation of T-lymphocytes in response to antigenic or mitogenic stimulation in vitro. [NIH] 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] Tardive: Marked by lateness, late; said of a disease in which the characteristic lesion is late in appearing. [EU] Telangiectasia: The permanent enlargement of blood vessels, causing redness in the skin or
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mucous membranes. [NIH] Temporal: One of the two irregular bones forming part of the lateral surfaces and base of the skull, and containing the organs of hearing. [NIH] Temporal Lobe: Lower lateral part of the cerebral hemisphere. [NIH] Tendon: A discrete band of connective tissue mainly composed of parallel bundles of collagenous fibers by which muscles are attached, or two muscles bellies joined. [NIH] Teratogenic: Tending to produce anomalies of formation, or teratism (= anomaly of formation or development : condition of a monster). [EU] Terbutaline: A selective beta-2 adrenergic agonist used as a bronchodilator and tocolytic. [NIH]
Testis: Either of the paired male reproductive glands that produce the male germ cells and the male hormones. [NIH] Testosterone: A hormone that promotes the development and maintenance of male sex characteristics. [NIH] Tetrahydrocannabinol: A psychoactive compound extracted from the resin of Cannabis sativa (marihuana, hashish). The isomer delta-9-tetrahydrocannabinol (THC) is considered the most active form, producing characteristic mood and perceptual changes associated with this compound. Dronabinol is a synthetic form of delta-9-THC. [NIH] Thalamic: Cell that reaches the lateral nucleus of amygdala. [NIH] Thalamic Diseases: Disorders of the centrally located thalamus, which integrates a wide range of cortical and subcortical information. Manifestations include sensory loss, movement disorders; ataxia, pain syndromes, visual disorders, a variety of neuropsychological conditions, and coma. Relatively common etiologies include cerebrovascular disorders; craniocerebral trauma; brain neoplasms; brain hypoxia; intracranial hemorrhages; and infectious processes. [NIH] Thalidomide: A pharmaceutical agent originally introduced as a non-barbiturate hypnotic, but withdrawn from the market because of its known tetratogenic effects. It has been reintroduced and used for a number of immunological and inflammatory disorders. Thalidomide displays immunosuppresive and anti-angiogenic activity. It inhibits release of tumor necrosis factor alpha from monocytes, and modulates other cytokine action. [NIH] Therapeutics: The branch of medicine which is concerned with the treatment of diseases, palliative or curative. [NIH] Thermal: Pertaining to or characterized by heat. [EU] Thiamphenicol: A methylsulfonyl analog of chloramphenicol. It is an antibiotic and immunosuppressive agent. [NIH] Thimerosal: A topical antiseptic used on skin and mucous membranes. It is also used as a preservative in pharmaceuticals. [NIH] Thioredoxin: A hydrogen-carrying protein that participates in a variety of biochemical reactions including ribonucleotide reduction. Thioredoxin is oxidized from a dithiol to a disulfide during ribonucleotide reduction. The disulfide form is then reduced by NADPH in a reaction catalyzed by thioredoxin reductase. [NIH] Thiotepa: A very toxic alkylating antineoplastic agent also used as an insect sterilant. It causes skin, gastrointestinal, CNS, and bone marrow damage. According to the Fourth Annual Report on Carcinogens (NTP 85-002, 1985), thiotepa may reasonably be anticipated to be a carcinogen (Merck Index, 11th ed). [NIH] Third Ventricle: A narrow cleft inferior to the corpus callosum, within the diencephalon,
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between the paired thalami. Its floor is formed by the hypothalamus, its anterior wall by the lamina terminalis, and its roof by ependyma. It communicates with the fourth ventricle by the cerebral aqueduct, and with the lateral ventricles by the interventricular foramina. [NIH] Thoracic: Having to do with the chest. [NIH] Thorax: A part of the trunk between the neck and the abdomen; the chest. [NIH] Threonine: An essential amino acid occurring naturally in the L-form, which is the active form. It is found in eggs, milk, gelatin, and other proteins. [NIH] Threshold: For a specified sensory modality (e. g. light, sound, vibration), the lowest level (absolute threshold) or smallest difference (difference threshold, difference limen) or intensity of the stimulus discernible in prescribed conditions of stimulation. [NIH] Thrombin: An enzyme formed from prothrombin that converts fibrinogen to fibrin. (Dorland, 27th ed) EC 3.4.21.5. [NIH] Thrombolytic: 1. Dissolving or splitting up a thrombus. 2. A thrombolytic agent. [EU] Thrombomodulin: A cell surface glycoprotein of endothelial cells that binds thrombin and serves as a cofactor in the activation of protein C and its regulation of blood coagulation. [NIH]
Thrombosis: The formation or presence of a blood clot inside a blood vessel. [NIH] Thromboxanes: Physiologically active compounds found in many organs of the body. They are formed in vivo from the prostaglandin endoperoxides and cause platelet aggregation, contraction of arteries, and other biological effects. Thromboxanes are important mediators of the actions of polyunsaturated fatty acids transformed by cyclooxygenase. [NIH] Thrombus: An aggregation of blood factors, primarily platelets and fibrin with entrapment of cellular elements, frequently causing vascular obstruction at the point of its formation. Some authorities thus differentiate thrombus formation from simple coagulation or clot formation. [EU] Thrush: A disease due to infection with species of fungi of the genus Candida. [NIH] Thymidine: A chemical compound found in DNA. Also used as treatment for mucositis. [NIH]
Thymidine Kinase: An enzyme that catalyzes the conversion of ATP and thymidine to ADP and thymidine 5'-phosphate. Deoxyuridine can also act as an acceptor and dGTP as a donor. (From Enzyme Nomenclature, 1992) EC 2.7.1.21. [NIH] Thymus: An organ that is part of the lymphatic system, in which T lymphocytes grow and multiply. The thymus is in the chest behind the breastbone. [NIH] Thyroid: A gland located near the windpipe (trachea) that produces thyroid hormone, which helps regulate growth and metabolism. [NIH] Thyroid Gland: A highly vascular endocrine gland consisting of two lobes, one on either side of the trachea, joined by a narrow isthmus; it produces the thyroid hormones which are concerned in regulating the metabolic rate of the body. [NIH] Thyroxine: An amino acid of the thyroid gland which exerts a stimulating effect on thyroid metabolism. [NIH] Ticks: Blood-sucking arachnids of the order Acarina. [NIH] Timolol: A beta-adrenergic antagonist similar in action to propranolol. The levo-isomer is the more active. Timolol has been proposed as an antihypertensive, antiarrhythmic, antiangina, and antiglaucoma agent. It is also used in the treatment of migraine and tremor. [NIH]
Tinnitus: Sounds that are perceived in the absence of any external noise source which may
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take the form of buzzing, ringing, clicking, pulsations, and other noises. Objective tinnitus refers to noises generated from within the ear or adjacent structures that can be heard by other individuals. The term subjective tinnitus is used when the sound is audible only to the affected individual. Tinnitus may occur as a manifestation of cochlear diseases; vestibulocochlear nerve diseases; intracranial hypertension; craniocerebral trauma; and other conditions. [NIH] Tissue: A group or layer of cells that are alike in type and work together to perform a specific function. [NIH] Tissue Culture: Maintaining or growing of tissue, organ primordia, or the whole or part of an organ in vitro so as to preserve its architecture and/or function (Dorland, 28th ed). Tissue culture includes both organ culture and cell culture. [NIH] Tissue Expansion: Process whereby tissue adjacent to a soft tissue defect is expanded by means of a subcutaneously implanted reservoir. The procedure is used in reconstructive surgery for injuries caused by trauma, burns, or ablative surgery. [NIH] Tissue Transplantation: Transference of tissue within an individual, between individuals of the same species, or between individuals of different species. [NIH] Tobramycin: An aminoglycoside, broad-spectrum antibiotic produced by Streptomyces tenebrarius. It is effective against gram-negative bacteria, especially the Pseudomonas species. It is a 10% component of the antibiotic complex, nebramycin, produced by the same species. [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] Tone: 1. The normal degree of vigour and tension; in muscle, the resistance to passive elongation or stretch; tonus. 2. A particular quality of sound or of voice. 3. To make permanent, or to change, the colour of silver stain by chemical treatment, usually with a heavy metal. [EU] Tonic: 1. Producing and restoring the normal tone. 2. Characterized by continuous tension. 3. A term formerly used for a class of medicinal preparations believed to have the power of restoring normal tone to tissue. [EU] Tonicity: The normal state of muscular tension. [NIH] Tonus: A state of slight tension usually present in muscles even when they are not undergoing active contraction. [NIH] Topical: On the surface of the body. [NIH] Topoisomerase inhibitors: A family of anticancer drugs. The topoisomerase enzymes are responsible for the arrangement and rearrangement of DNA in the cell and for cell growth and replication. Inhibiting these enzymes may kill cancer cells or stop their growth. [NIH] Topotecan: An antineoplastic agent used to treat ovarian cancer. It works by inhibiting DNA topoisomerase. [NIH] Torsion: A twisting or rotation of a bodily part or member on its axis. [NIH] Toxic: Having to do with poison or something harmful to the body. Toxic substances usually cause unwanted side effects. [NIH] Toxicity: The quality of being poisonous, especially the degree of virulence of a toxic microbe or of a poison. [EU] Toxicology: The science concerned with the detection, chemical composition, and pharmacologic action of toxic substances or poisons and the treatment and prevention of
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toxic manifestations. [NIH] Toxin: A poison; frequently used to refer specifically to a protein produced by some higher plants, certain animals, and pathogenic bacteria, which is highly toxic for other living organisms. Such substances are differentiated from the simple chemical poisons and the vegetable alkaloids by their high molecular weight and antigenicity. [EU] Trabecular Meshwork: A porelike structure surrounding the entire circumference of the anterior chamber through which aqueous humor circulates to the canal of Schlemm. [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] Traction: The act of pulling. [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] 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 alpha: Factor isolated in a variety of tissues including epithelium, and maternal decidua. It is closely related to epidermal growth factor and binds to the EGF receptor. TGF-alpha acts synergistically with TGF-beta in inducing phenotypic transformation, but its physiological role is unknown. [NIH] Transfusion: The infusion of components of blood or whole blood into the bloodstream. The blood may be donated from another person, or it may have been taken from the person earlier and stored until needed. [NIH] Translation: The process whereby the genetic information present in the linear sequence of ribonucleotides in mRNA is converted into a corresponding sequence of amino acids in a protein. It occurs on the ribosome and is unidirectional. [NIH] Translational: The cleavage of signal sequence that directs the passage of the protein through a cell or organelle membrane. [NIH] Translocation: The movement of material in solution inside the body of the plant. [NIH] Transmitter: A chemical substance which effects the passage of nerve impulses from one cell to the other at the synapse. [NIH] Transplantation: Transference of a tissue or organ, alive or dead, within an individual, between individuals of the same species, or between individuals of different species. [NIH] Trauma: Any injury, wound, or shock, must frequently physical or structural shock, producing a disturbance. [NIH] Tremor: Cyclical movement of a body part that can represent either a physiologic process or a manifestation of disease. Intention or action tremor, a common manifestation of cerebellar
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diseases, is aggravated by movement. In contrast, resting tremor is maximal when there is no attempt at voluntary movement, and occurs as a relatively frequent manifestation of Parkinson disease. [NIH] 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] Tricyclic: Containing three fused rings or closed chains in the molecular structure. [EU] Trigeminal: Cranial nerve V. It is sensory for the eyeball, the conjunctiva, the eyebrow, the skin of face and scalp, the teeth, the mucous membranes in the mouth and nose, and is motor to the muscles of mastication. [NIH] Trigeminal Nerve: The 5th and largest cranial nerve. The trigeminal nerve is a mixed motor and sensory nerve. The larger sensory part forms the ophthalmic, mandibular, and maxillary nerves which carry afferents sensitive to external or internal stimuli from the skin, muscles, and joints of the face and mouth and from the teeth. Most of these fibers originate from cells of the trigeminal ganglion and project to the trigeminal nucleus of the brain stem. The smaller motor part arises from the brain stem trigeminal motor nucleus and innervates the muscles of mastication. [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] Trophoblast: The outer layer of cells of the blastocyst which works its way into the endometrium during ovum implantation and grows rapidly, later combining with mesoderm. [NIH] Tropomyosin: A protein found in the thin filaments of muscle fibers. It inhibits contraction of the muscle unless its position is modified by troponin. [NIH] Troponin: One of the minor protein components of skeletal muscle. Its function is to serve as the calcium-binding component in the troponin-tropomyosin B-actin-myosin complex by conferring calcium sensitivity to the cross-linked actin and myosin filaments. [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] 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] Tubulin: A microtubule subunit protein found in large quantities in mammalian brain. It has also been isolated from sperm flagella, cilia, and other sources. Structurally, the protein is a dimer with a molecular weight of approximately 120,000 and a sedimentation coefficient of 5.8S. It binds to colchicine, vincristine, and vinblastine. [NIH] Tumor model: A type of animal model which can be used to study the development and progression of diseases and to test new treatments before they are given to humans. Animals with transplanted human cancers or other tissues are called xenograft models. [NIH] Tumor Necrosis Factor: Serum glycoprotein produced by activated macrophages and other mammalian mononuclear leukocytes which has necrotizing activity against tumor cell lines and increases ability to reject tumor transplants. It mimics the action of endotoxin but differs from it. It has a molecular weight of less than 70,000 kDa. [NIH] Tumor suppressor gene: Genes in the body that can suppress or block the development of cancer. [NIH]
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Tumour: 1. Swelling, one of the cardinal signs of inflammations; morbid enlargement. 2. A new growth of tissue in which the multiplication of cells is uncontrolled and progressive; called also neoplasm. [EU] Tunica: A rather vague term to denote the lining coat of hollow organs, tubes, or cavities. [NIH]
Tympanic membrane: A thin, tense membrane forming the greater part of the outer wall of the tympanic cavity and separating it from the external auditory meatus; it constitutes the boundary between the external and middle ear. [NIH] Tyramine: An indirect sympathomimetic. Tyramine does not directly activate adrenergic receptors, but it can serve as a substrate for adrenergic uptake systems and monoamine oxidase so it prolongs the actions of adrenergic transmitters. It also provokes transmitter release from adrenergic terminals. Tyramine may be a neurotransmitter in some invertebrate nervous systems. [NIH] Tyrosine: A non-essential amino acid. In animals it is synthesized from phenylalanine. It is also the precursor of epinephrine, thyroid hormones, and melanin. [NIH] Tyrothricin: A polypeptide antibiotic mixture obtained from Bacillus brevis. It consists of a mixture of three tyrocidines (60%) and several gramicidins (20%) and is very toxic to blood, liver, kidneys, meninges, and the olfactory apparatus. It is used topically. [NIH] Ubiquitin: A highly conserved 76 amino acid-protein found in all eukaryotic cells. [NIH] Ulcerative colitis: Chronic inflammation of the colon that produces ulcers in its lining. This condition is marked by abdominal pain, cramps, and loose discharges of pus, blood, and mucus from the bowel. [NIH] Ultrasonography: The visualization of deep structures of the body by recording the reflections of echoes of pulses of ultrasonic waves directed into the tissues. Use of ultrasound for imaging or diagnostic purposes employs frequencies ranging from 1.6 to 10 megahertz. [NIH] Ultrasound test: A test that bounces sound waves off tissues and internal organs and changes the echoes into pictures (sonograms). [NIH] Unconscious: Experience which was once conscious, but was subsequently rejected, as the "personal unconscious". [NIH] Unresectable: Unable to be surgically removed. [NIH] Urea: A compound (CO(NH2)2), formed in the liver from ammonia produced by the deamination of amino acids. It is the principal end product of protein catabolism and constitutes about one half of the total urinary solids. [NIH] Uremia: The illness associated with the buildup of urea in the blood because the kidneys are not working effectively. Symptoms include nausea, vomiting, loss of appetite, weakness, and mental confusion. [NIH] Ureters: Tubes that carry urine from the kidneys to the bladder. [NIH] Urethra: The tube through which urine leaves the body. It empties urine from the bladder. [NIH]
Urinary: Having to do with urine or the organs of the body that produce and get rid of urine. [NIH] Urinary tract: The organs of the body that produce and discharge urine. These include the kidneys, ureters, bladder, and urethra. [NIH] 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]
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Uteroglobin: A protein fraction of pregnant uterine fluid which can induce and regulate blastocystic development. Blastokinin is thought to be similar or identical to uteroglobin. Presence in uterine fluid regulated by progesterone. [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] Uvea: The middle coat of the eyeball, consisting of the choroid in the back of the eye and the ciliary body and iris in the front of the eye. [NIH] Uveal tract: The middle coat of the eyeball, consisting of the choroid in the back of the eye and the ciliary body and iris in the front of the eye. [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] 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] Vagus Nerve: The 10th cranial nerve. The vagus is a mixed nerve which contains somatic afferents (from skin in back of the ear and the external auditory meatus), visceral afferents (from the pharynx, larynx, thorax, and abdomen), parasympathetic efferents (to the thorax and abdomen), and efferents to striated muscle (of the larynx and pharynx). [NIH] Vancomycin: Antibacterial obtained from Streptomyces orientalis. It is a glycopeptide related to ristocetin that inhibits bacterial cell wall assembly and is toxic to kidneys and the inner ear. [NIH] Vascular: Pertaining to blood vessels or indicative of a copious blood supply. [EU] Vasoactive: Exerting an effect upon the calibre of blood vessels. [EU] Vasoactive Intestinal Peptide: A highly basic, single-chain polypeptide isolated from the intestinal mucosa. It has a wide range of biological actions affecting the cardiovascular, gastrointestinal, and respiratory systems. It is also found in several parts of the central and peripheral nervous systems and is a neurotransmitter. [NIH] Vasoconstriction: Narrowing of the blood vessels without anatomic change, for which constriction, pathologic is used. [NIH] Vasodilators: Any nerve or agent which induces dilatation of the blood vessels. [NIH] VE: The total volume of gas either inspired or expired in one minute. [NIH] Vector: Plasmid or other self-replicating DNA molecule that transfers DNA between cells in nature or in recombinant DNA technology. [NIH] Vegetative: 1. Concerned with growth and with nutrition. 2. Functioning involuntarily or unconsciously, as the vegetative nervous system. 3. Resting; denoting the portion of a cell cycle during which the cell is not involved in replication. 4. Of, pertaining to, or characteristic of plants. [EU] Vein: Vessel-carrying blood from various parts of the body to the heart. [NIH] Venous: Of or pertaining to the veins. [EU] Venous blood: Blood that has given up its oxygen to the tissues and carries carbon dioxide back for gas exchange. [NIH] 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
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alveoli, in which gas exchange with the blood takes place. 2. In psychiatry, verbalization of one's emotional problems. [EU] Ventricle: One of the two pumping chambers of the heart. The right ventricle receives oxygen-poor blood from the right atrium and pumps it to the lungs through the pulmonary artery. The left ventricle receives oxygen-rich blood from the left atrium and pumps it to the body through the aorta. [NIH] Ventricular: Pertaining to a ventricle. [EU] Ventricular Dysfunction: A condition in which the ventricles of the heart exhibit a decreased functionality. [NIH] Venules: The minute vessels that collect blood from the capillary plexuses and join together to form veins. [NIH] Verapamil: A calcium channel blocker that is a class IV anti-arrhythmia agent. [NIH] Vertebrae: A bony unit of the segmented spinal column. [NIH] Vertigo: An illusion of movement; a sensation as if the external world were revolving around the patient (objective vertigo) or as if he himself were revolving in space (subjective vertigo). The term is sometimes erroneously used to mean any form of dizziness. [EU] Vesicular: 1. Composed of or relating to small, saclike bodies. 2. Pertaining to or made up of vesicles on the skin. [EU] 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] Vestibulocochlear Nerve: The 8th cranial nerve. The vestibulocochlear nerve has a cochlear part (cochlear nerve) which is concerned with hearing and a vestibular part (vestibular nerve) which mediates the sense of balance and head position. The fibers of the cochlear nerve originate from neurons of the spiral ganglion and project to the cochlear nuclei (cochlear nucleus). The fibers of the vestibular nerve arise from neurons of Scarpa's ganglion and project to the vestibular nuclei. [NIH] Veterinary Medicine: The medical science concerned with the prevention, diagnosis, and treatment of diseases in animals. [NIH] Vial: A small bottle. [EU] Vinblastine: An anticancer drug that belongs to the family of plant drugs called vinca alkaloids. It is a mitotic inhibitor. [NIH] Vinca Alkaloids: A class of alkaloids from the genus of apocyanaceous woody herbs including periwinkles. They are some of the most useful antineoplastic agents. [NIH] Vincristine: An anticancer drug that belongs to the family of plant drugs called vinca alkaloids. [NIH] Vinorelbine: 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 Load: The quantity of measurable virus in the blood. Change in viral load, measured in plasma, is used as a surrogate marker in HIV disease progression. [NIH] Viral vector: A type of virus used in cancer therapy. The virus is changed in the laboratory and cannot cause disease. Viral vectors produce tumor antigens (proteins found on a tumor cell) and can stimulate an antitumor immune response in the body. Viral vectors may also
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be used to carry genes that can change cancer cells back to normal cells. [NIH] Virilism: Development of masculine traits in the female. [NIH] Virulence: The degree of pathogenicity within a group or species of microorganisms or viruses as indicated by case fatality rates and/or the ability of the organism to invade the tissues of the host. [NIH] Virus: Submicroscopic organism that causes infectious disease. In cancer therapy, some viruses may be made into vaccines that help the body build an immune response to, and kill, tumor cells. [NIH] Visceral: , from viscus a viscus) pertaining to a viscus. [EU] Visceral Afferents: The sensory fibers innervating the viscera. [NIH] Viscosity: A physical property of fluids that determines the internal resistance to shear forces. [EU] Vitamin A: A substance used in cancer prevention; it belongs to the family of drugs called retinoids. [NIH] Vitreoretinal: A rare familial condition characterized by a clear vitreous, except for preretinal filaments and veils which have been loosened from the retina, a dense hyaloid membrane which is perforated and detached, and masses of peripheral retinal pigmentation inters. [NIH] Vitreous: Glasslike or hyaline; often used alone to designate the vitreous body of the eye (corpus vitreum). [EU] Vitro: Descriptive of an event or enzyme reaction under experimental investigation occurring outside a living organism. Parts of an organism or microorganism are used together with artificial substrates and/or conditions. [NIH] Vivo: Outside of or removed from the body of a living organism. [NIH] Voltage-gated: It is opened by the altered charge distribution across the cell membrane. [NIH]
War: Hostile conflict between organized groups of people. [NIH] Warts: Benign epidermal proliferations or tumors; some are viral in origin. [NIH] Water Deprivation: The withholding of water in a structured experimental situation. [NIH] White blood cell: A type of cell in the immune system that helps the body fight infection and disease. White blood cells include lymphocytes, granulocytes, macrophages, and others. [NIH]
Windpipe: A rigid tube, 10 cm long, extending from the cricoid cartilage to the upper border of the fifth thoracic vertebra. [NIH] Withdrawal: 1. A pathological retreat from interpersonal contact and social involvement, as may occur in schizophrenia, depression, or schizoid avoidant and schizotypal personality disorders. 2. (DSM III-R) A substance-specific organic brain syndrome that follows the cessation of use or reduction in intake of a psychoactive substance that had been regularly used to induce a state of intoxication. [EU] Wound Healing: Restoration of integrity to traumatized tissue. [NIH] Xanthine: An urinary calculus. [NIH] Xenobiotics: Chemical substances that are foreign to the biological system. They include naturally occurring compounds, drugs, environmental agents, carcinogens, insecticides, etc. [NIH]
Xenograft: The cells of one species transplanted to another species. [NIH]
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X-ray: High-energy radiation used in low doses to diagnose diseases and in high doses to treat cancer. [NIH] Yeasts: A general term for single-celled rounded fungi that reproduce by budding. Brewers' and bakers' yeasts are Saccharomyces cerevisiae; therapeutic dried yeast is dried yeast. [NIH] Yolk Sac: An embryonic membrane formed from endoderm and mesoderm. In reptiles and birds it incorporates the yolk into the digestive tract for nourishing the embryo. In placental mammals its nutritional function is vestigial; however, it is the source of most of the intestinal mucosa and the site of formation of the germ cells. It is sometimes called the vitelline sac, which should not be confused with the vitelline membrane of the egg. [NIH] Zoonoses: Diseases of non-human animals that may be transmitted to man or may be transmitted from man to non-human animals. [NIH] Zygote: The fertilized ovum. [NIH] Zymogen: Inactive form of an enzyme which can then be converted to the active form, usually by excision of a polypeptide, e. g. trypsinogen is the zymogen of trypsin. [NIH]
323
INDEX A Abdomen, 140, 215, 229, 235, 251, 266, 270, 274, 288, 290, 291, 303, 308, 309, 313, 318 Abdominal, 144, 185, 215, 216, 235, 245, 258, 288, 291, 303, 317 Abdominal Pain, 215, 258, 317 Aberrant, 33, 54, 215 Ablation, 157, 215 Acantholysis, 215, 290 Acceptor, 215, 274, 287, 313, 315 Acetone, 162, 215, 272 Acetylcholine, 41, 215, 235, 284, 285 Acetylglucosamine, 164, 215 Acne, 215, 271 Acne Vulgaris, 215, 271 Acquired Immunodeficiency Syndrome, 92, 126, 152, 215 Actin, 98, 215, 282, 316 Acute leukemia, 66, 120, 215, 251, 296 Acute lymphoblastic leukemia, 74, 81, 82, 94, 112, 121, 123, 129, 137, 215, 216 Acute lymphocytic leukemia, 72, 121, 215 Acute myelogenous leukemia, 59, 216 Acute myeloid leukemia, 216 Acute nonlymphocytic leukemia, 216 Adaptability, 216, 233, 234 Adaptation, 216, 294 Adenocarcinoma, 63, 136, 216 Adenosine, 216, 224, 231, 292 Adipocytes, 27, 216, 240, 273 Adipose Tissue, 27, 134, 216, 230 Adjunctive Therapy, 64, 216 Adjuvant, 9, 52, 100, 127, 216, 258 Adrenal Cortex, 6, 216, 217, 242, 253, 264, 265, 296, 302 Adrenal Glands, 19, 149, 150, 187, 216, 219 Adrenal Medulla, 18, 216, 233, 251, 285 Adrenergic, 65, 84, 155, 156, 216, 221, 226, 247, 251, 297, 311, 312, 313, 317 Adrenergic Agents, 155, 216 Adverse Effect, 9, 26, 159, 184, 216, 271, 292, 306 Aerobic, 19, 217, 253, 285, 288 Aerosol, 103, 217, 226, 311 Afferent, 38, 40, 154, 217, 273 Afferent Pathways, 38, 217 Affinity, 4, 50, 167, 217, 224, 274, 276, 279, 307
Agar, 217, 242, 293 Agonist, 33, 149, 150, 165, 167, 217, 226, 230, 237, 247, 282, 293, 311, 312 Agoraphobia, 217, 266, 289 Air Pressure, 217, 253 Airway, 17, 41, 52, 70, 73, 84, 99, 105, 217, 230 Albumin, 163, 217, 293 Aldosterone, 217, 260, 280 Alertness, 217, 230 Algorithms, 217, 227 Alimentary, 90, 217, 290 Alkaline, 102, 218, 219, 231, 288, 292 Alkaline Phosphatase, 102, 218 Alkaloid, 156, 218, 224, 230, 231, 232, 238, 281, 305 Alkylating Agents, 218, 232 Allantois, 218, 255 Alleles, 218, 263 Allergen, 218, 245 Allergic Rhinitis, 218, 230 Allogeneic, 163, 218, 261 Allograft, 218, 264 Allylamine, 218, 219 Alopecia, 218, 243 Alpha Particles, 218, 300 Alpha-1, 51, 218, 243 Alpha-Defensins, 218, 244 Alpha-fetoprotein, 61, 218, 255 Alternative medicine, 186, 218 Alveolar Process, 218, 302 Alveoli, 218, 319 Ameliorating, 53, 218 Amenorrhea, 166, 219, 294 Amine, 150, 219, 264 Amino Acid Sequence, 219, 220, 221, 226, 258, 296, 306 Amino-terminal, 219, 296 Ammonia, 162, 219, 260, 311, 317 Amnion, 219, 255 Amniotic Fluid, 19, 219, 259 Amoxicillin, 171, 219 Amphetamine, 219, 227 Ampicillin, 116, 219 Amplification, 54, 219 Ampulla, 219, 250 Amygdala, 58, 219, 226, 274, 312 Amyloidosis, 129, 219
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Anabolic, 34, 220, 246, 256 Anaesthesia, 75, 79, 80, 86, 89, 102, 110, 220, 267 Anal, 17, 220 Analgesic, 69, 220, 230, 245, 281, 286 Analog, 56, 168, 220, 230, 237, 256, 312 Analogous, 159, 220, 315 Anaphylatoxins, 220, 239 Anaplastic, 138, 220 Anaplastic large cell lymphoma, 138, 220 Anatomical, 220, 224, 235, 267, 279, 284, 293, 305 Anchorage, 68, 220 Androgen-Binding Protein, 220, 306 Androgens, 5, 216, 220, 242, 265 Anemia, 141, 201, 220, 230, 256, 281 Anesthesia, 16, 39, 66, 69, 98, 99, 106, 109, 110, 111, 127, 217, 220, 221, 224, 250, 295, 296 Anesthetics, 220, 226, 235, 251 Angiogenesis, 7, 36, 37, 220, 277 Angiogenesis inhibitor, 36, 220 Angioplasty, 157, 168, 169, 221, 224 Angiotensinogen, 221, 302 Animal model, 14, 17, 26, 37, 47, 48, 53, 221, 316 Anions, 217, 221, 226, 271, 306 Ankyrin Repeat, 35, 221 Anomalies, 25, 221, 312 Anorexia, 51, 103, 185, 221, 258 Anovulation, 221, 294 Antagonism, 221, 231 Anterior chamber, 156, 221, 271, 315 Anthracycline, 221, 244, 251 Anti-Anxiety Agents, 221, 296 Antiarrhythmic, 221, 313 Antibacterial, 221, 237, 260, 285, 286, 308, 318 Antibiotic Prophylaxis, 221, 296 Antibodies, 37, 55, 137, 168, 174, 221, 262, 266, 275, 281, 293, 300 Antibody therapy, 138, 222 Anticholinergic, 144, 222 Anticoagulant, 222, 298 Anticonvulsant, 222, 232, 292 Antidepressant, 222, 237, 266 Antidote, 222, 273 Antiemetic, 15, 66, 68, 69, 102, 104, 140, 144, 161, 176, 222, 246, 261, 279 Antifungal, 12, 222, 243, 307
Antigen, 11, 17, 32, 41, 60, 86, 125, 171, 217, 221, 222, 239, 264, 265, 266, 267, 269, 278, 280 Antigen-Antibody Complex, 222, 239 Antigen-presenting cell, 11, 17, 222 Antihistamine, 144, 222 Antihypertensive, 222, 313 Anti-infective, 222, 231, 265 Anti-Inflammatory Agents, 161, 222, 233, 242, 272 Antimetabolite, 222, 256, 279 Antimicrobial, 83, 161, 175, 222, 236, 244, 292 Antineoplastic Agents, 27, 218, 222, 319 Antioxidant, 41, 122, 129, 222, 224, 257, 288 Antiproliferative, 110, 168, 222 Antipruritic, 66, 223, 231 Antipyretic, 223, 245 Antiseptic, 215, 223, 292, 312 Antispasmodic, 223, 286, 305 Antitussive, 223, 246, 286 Antiviral, 223, 260, 269 Anus, 220, 223, 224, 229, 238, 255, 291, 301 Anxiety, 51, 97, 154, 221, 223, 288, 297 Anxiety Disorders, 51, 223, 289 Anxiolytic, 223, 286 Aorta, 146, 223, 232, 241, 319 Aponeurosis, 223, 257 Applicability, 25, 223 Aqueous, 47, 156, 162, 171, 223, 226, 236, 243, 249, 265, 273, 315 Aqueous humor, 47, 156, 223, 236, 315 Arachidonic Acid, 168, 173, 223, 248, 265, 273, 297 Arginine, 23, 220, 223, 285 Aromatic, 223, 227, 252, 279, 292 Arrhythmia, 221, 223, 319 Arsenic trioxide, 136, 223 Arterial, 50, 100, 127, 138, 155, 157, 218, 223, 241, 256, 265, 298, 311 Arteries, 146, 157, 223, 228, 232, 241, 275, 279, 282, 299, 313 Arteriolar, 223, 229, 302 Arterioles, 223, 228 Artery, 74, 146, 157, 168, 169, 221, 223, 232, 241, 249, 250, 255, 277, 299, 304 Arthralgia, 173, 224 Articular, 40, 45, 224, 287 Ascorbic Acid, 163, 224, 265 Aseptic, 224, 286, 309 Asparaginase, 126, 224
Index 325
Aspartate, 224 Aspirate, 84, 224 Assay, 4, 7, 12, 29, 57, 224, 304 Astrocytes, 224, 276, 279, 281 Asymptomatic, 55, 224 Ataxia, 200, 201, 224, 312 Atherectomy, 157, 224, 250 ATP, 104, 224, 247, 259, 271, 292, 298, 313 Atresia, 56, 224 Atrial, 224, 241, 311, 316 Atrioventricular, 55, 137, 224, 241 Atrium, 224, 232, 241, 316, 319 Atrophy, 14, 116, 200, 215, 224, 252 Atropine, 224, 305 Attenuation, 19, 61, 69, 225 Atypical, 39, 64, 225 Auditory, 225, 262, 277, 317, 318 Aurothioglucose, 52, 225 Autacoids, 225, 267 Autoimmune disease, 41, 150, 165, 171, 225 Autoimmunity, 55, 225 Autologous, 74, 91, 126, 163, 225 Autonomic, 15, 38, 50, 215, 225, 284, 285, 291 Autonomic Nervous System, 225, 291 Avian, 29, 225 Axons, 225, 244, 283 B Bacterial Infections, 161, 225, 234 Bactericidal, 9, 225, 253, 285 Bacteriophage, 225, 293, 315 Bacteriostatic, 225, 252 Bacterium, 151, 225, 240 Balloon dilation, 157, 225 Band 3 Protein, 221, 225 Barbiturate, 226, 312 Basal Ganglia, 224, 226, 257, 274 Basal Ganglia Diseases, 224, 226 Base, 53, 226, 244, 253, 258, 271, 291, 292, 312 Basement Membrane, 226, 254, 272 Basophils, 226, 261, 273 Beclomethasone, 103, 226 Benign, 225, 226, 257, 262, 283, 300, 320 Benign prostatic hyperplasia, 225, 226 Benzyl Alcohol, 156, 226 Beta-Defensins, 226, 244 Beta-Endorphin, 39, 226 Beta-Thromboglobulin, 226, 270 Betaxolol, 155, 226 Bilateral, 227, 252, 289, 294
Bile, 25, 57, 227, 257, 274, 309 Bile Acids, 57, 227, 309 Bile Acids and Salts, 227 Bile duct, 25, 227 Biliary, 13, 25, 146, 175, 227 Biliary Tract, 146, 227 Bilirubin, 217, 227 Binding Sites, 10, 48, 227 Bioartificial Organs, 175, 227 Bioassay, 52, 227 Bioavailable, 37, 227 Biochemical reactions, 227, 312 Biogenic Amines, 150, 227 Biological response modifier, 227, 269 Biological therapy, 227, 261 Biopsy, 227, 290 Biotechnology, 59, 65, 164, 180, 186, 197, 199, 200, 201, 227 Biotin, 163, 228 Bipolar Disorder, 10, 228 Bivalent, 228, 279 Bladder, 148, 225, 226, 228, 239, 267, 298, 317 Blastocyst, 228, 240, 287, 293, 316 Bleomycin, 48, 66, 119, 228 Blister, 228, 290 Blood Coagulation, 228, 231, 255, 304, 313 Blood Coagulation Factors, 228 Blood Glucose, 228, 262, 269 Blood Platelets, 228, 278, 306 Blood pressure, 49, 83, 155, 222, 228, 232, 265, 266, 280, 299, 307 Blood Proteins, 137, 228 Blood Volume, 36, 228 Blood-Brain Barrier, 139, 228 Blot, 57, 228 Body Fluids, 228, 230, 248, 307 Body Mass Index, 228, 287 Bolus, 19, 102, 122, 128, 228, 229 Bolus infusion, 228 Bolus injection, 102, 128, 229 Bone Marrow Cells, 116, 229, 261, 278 Bone Marrow Transplantation, 59, 122, 123, 128, 229 Bone metastases, 73, 229 Bone scan, 73, 229 Boron, 229, 242 Bowel, 38, 52, 79, 220, 229, 246, 257, 270, 291, 309, 317 Bowel Movement, 229, 246, 309 Brachytherapy, 229, 270, 271, 300 Bradykinin, 70, 229, 285, 293
326
Dexamethasone
Brain Stem, 16, 229, 316 Branch, 211, 229, 243, 275, 277, 289, 299, 308, 312 Breakdown, 27, 52, 229, 246, 257 Breast Neoplasms, 229, 256 Breast reconstruction, 149, 229 Breeding, 158, 170, 229 Broad-spectrum, 219, 229, 233, 286, 314 Bronchi, 229, 230, 251, 315 Bronchial, 75, 98, 104, 229, 230, 264 Bronchitis, 17, 230, 236 Bronchoconstriction, 41, 230 Bronchodilator, 230, 312 Bronchopulmonary, 105, 106, 230 Bronchopulmonary Dysplasia, 105, 106, 230 Bronchospasm, 52, 230 Bronchus, 230 Brown Fat, 18, 230 Buccal, 230, 275 Budesonide, 14, 60, 185, 230 Bullous, 20, 230 Bumetanide, 21, 230 Bupivacaine, 109, 110, 127, 230, 274 Buprenorphine, 24, 230 Burns, 230, 314 Buserelin, 72, 230 Bypass, 86, 230 C Cachexia, 185, 230 Cadmium, 148, 230 Cadmium Poisoning, 230 Caffeine, 159, 230, 299 Calcifediol, 231 Calcitriol, 59, 70, 136, 231 Calcium, 16, 33, 56, 62, 78, 125, 231, 239, 265, 273, 277, 287, 289, 306, 316, 319 Calcium channel blocker, 231, 319 Calcium Channels, 16, 56, 231 Calibration, 36, 231 Callus, 231, 249 Camphor, 231, 235 Camptothecin, 231, 271 Candidiasis, 12, 231 Candidosis, 231 Cannabidiol, 231, 232 Cannabinoids, 9, 231 Cannabinol, 232 Cannula, 146, 232 Capsaicin, 40, 232 Carbamazepine, 85, 232 Carbenoxolone, 50, 232
Carbohydrate, 164, 172, 232, 242, 259, 260, 295 Carbon Dioxide, 232, 244, 257, 293, 302, 318 Carboplatin, 91, 104, 138, 232 Carcinogen, 14, 232, 278, 312 Carcinogenesis, 25, 33, 232, 235 Carcinogenic, 160, 218, 232, 268, 286, 297, 309 Carcinoma, 69, 86, 98, 100, 127, 129, 232 Cardiac, 21, 48, 55, 56, 86, 91, 218, 221, 230, 232, 241, 249, 250, 251, 253, 257, 273, 282, 309 Cardiomyopathy, 232 Cardiopulmonary, 73, 80, 86, 232 Cardiopulmonary Bypass, 80, 86, 232 Cardioselective, 226, 232, 297 Cardiotoxicity, 232, 252 Cardiovascular, 7, 27, 46, 49, 104, 219, 231, 232, 253, 273, 306, 318 Cardiovascular disease, 27, 46, 49, 232 Carmustine, 123, 232 Carotid Arteries, 146, 232 Case report, 3, 105, 128, 233, 254 Caspase, 33, 57, 233 Catabolism, 34, 46, 52, 75, 233 Cataract, 87, 233 Catecholamine, 7, 18, 233, 247 Catheter, 138, 145, 146, 157, 224, 233, 250 Catheterization, 221, 233 Cations, 233, 271 Caudal, 233, 245, 266, 295 Ceftriaxone, 60, 63, 233 Celecoxib, 84, 233 Cell Adhesion, 16, 20, 70, 233, 269 Cell Adhesion Molecules, 16, 233 Cell Aggregation, 233, 287 Cell Death, 26, 29, 31, 35, 37, 44, 57, 82, 94, 107, 122, 129, 155, 223, 233, 253 Cell Differentiation, 163, 233, 306 Cell Division, 200, 225, 233, 234, 243, 253, 261, 280, 293 Cell Lineage, 15, 233 Cell membrane, 21, 231, 234, 245, 271, 292, 295, 307, 320 Cell motility, 234, 263 Cell Polarity, 38, 234 Cell proliferation, 29, 43, 51, 150, 169, 234, 270, 306 Cell Size, 234, 256 Cell Survival, 234, 261 Cell Transplantation, 175, 234
Index 327
Cellular adhesion, 85, 234 Cellulose, 234, 257, 293 Central Nervous System Infections, 234, 262 Centrifugation, 61, 234 Cerebellar, 224, 234, 301, 315 Cerebral, 19, 36, 62, 64, 84, 184, 185, 224, 226, 228, 229, 234, 235, 251, 253, 299, 312, 313 Cerebral Cortex, 224, 234, 253 Cerebral hemispheres, 226, 229, 234, 235 Cerebral Palsy, 19, 84, 184, 185, 234 Cerebrospinal, 23, 60, 83, 234, 275, 308 Cerebrospinal fluid, 23, 60, 83, 234, 275, 308 Cerebrovascular, 226, 232, 235, 312 Cerebrum, 234, 235, 316 Cervical, 158, 235 Cervix, 235 Cesarean Section, 20, 235 Character, 235, 244 Chemoprevention, 14, 235 Chemopreventive, 14, 120, 235 Chemotactic Factors, 235, 239, 285 Chemotaxis, 91, 235 Chemotherapeutic agent, 120, 144, 177, 235 Chest wall, 235, 302 Chickenpox, 152, 235 Chimeras, 44, 235 Chin, 116, 235, 278 Chlorobutanol, 147, 235 Chlorophyll, 235, 257 Cholecystectomy, 72, 75, 78, 101, 106, 235 Cholesterol, 227, 235, 241, 275, 278, 309, 311 Cholinergic, 58, 235, 289 Chondrocytes, 46, 87, 163, 236 Chondrosarcoma, 85, 236 Chorion, 236, 255 Chromaffin System, 236, 250 Chromatin, 11, 223, 236 Chromium, 124, 236 Chromosomal, 219, 236, 293, 303, 304 Chromosome, 236, 240, 274, 304 Chronic Disease, 230, 236, 238, 273 Chronic Fatigue Syndrome, 98, 236 Chronic lymphocytic leukemia, 89, 90, 108, 125, 236 Chronic Obstructive Pulmonary Disease, 94, 236 Chronic renal, 21, 236, 294
Ciliary, 80, 156, 223, 236, 306, 318 Ciliary Body, 156, 236, 306, 318 Ciliary processes, 223, 236 Ciprofloxacin, 112, 171, 176, 236 Circulatory system, 236, 250 CIS, 43, 44, 46, 60, 236, 266, 303 Cisplatin, 66, 73, 88, 112, 113, 119, 122, 123, 126, 128, 162, 236, 286 Citalopram, 6, 237 Citrus, 224, 237 Clamp, 21, 237 Clarithromycin, 113, 237 Clathrin, 237, 250 Clavulanic Acid, 171, 237 Clear cell carcinoma, 237, 246 Clinical trial, 4, 59, 135, 141, 197, 237, 241, 243, 247, 290, 298, 301 Clomiphene, 114, 237 Clone, 28, 31, 237 Cloning, 160, 227, 237 Cloprostenol, 158, 237 Coagulation, 9, 228, 237, 263, 293, 313 Coated Vesicles, 237, 250 Coca, 238 Cocaine, 39, 238 Cochlea, 29, 238, 268, 304 Cochlear, 30, 130, 238, 314, 319 Cod Liver Oil, 238, 249 Coenzyme, 224, 238, 272, 275 Cofactor, 238, 298, 313 Colitis, 204, 238 Collagen, 13, 22, 87, 164, 171, 219, 226, 238, 254, 255, 258, 264, 270, 277, 294, 296, 297 Collagen disease, 238, 264 Collagenases, 46, 238 Collapse, 169, 229, 238 Colloidal, 217, 238, 254, 291, 306, 311 Colon, 46, 57, 138, 146, 151, 200, 238, 273, 306, 317 Colorectal, 57, 100, 127, 129, 138, 238 Colorectal Cancer, 57, 100, 127, 138, 238 Combination chemotherapy, 137, 139, 238 Combination Therapy, 66, 120, 238 Comorbidity, 10, 39, 239 Complement, 11, 37, 39, 220, 239, 258, 269, 276, 293 Complement Activation, 11, 220, 239 Complementary and alternative medicine, 119, 132, 239 Complementary medicine, 119, 239 Complete remission, 8, 239, 302
328
Dexamethasone
Complete response, 239 Compliance, 10, 239 Computational Biology, 197, 199, 239 Concentration Camps, 240, 264 Conception, 240, 255, 309 Concomitant, 15, 165, 240 Conduction, 145, 240 Congestion, 240, 252 Conjugated, 128, 167, 168, 227, 240, 243, 303 Conjugation, 24, 240 Conjunctiva, 240, 268, 272, 299, 316 Conjunctivitis, 152, 240 Connective Tissue Cells, 240 Consciousness, 220, 221, 240, 244, 246, 299 Constipation, 240, 257 Constitutional, 58, 240 Constriction, 240, 271, 304, 318 Consumption, 41, 240, 245, 258, 288 Contamination, 147, 240 Continuous infusion, 113, 122, 240 Contractility, 19, 240, 248 Contraindications, ii, 240 Contralateral, 16, 240, 286, 301 Control group, 26, 241 Controlled study, 83, 97, 241 Cooperative group, 43, 241 Cor, 5, 6, 15, 19, 20, 23, 29, 38, 39, 50, 67, 92, 101, 149, 150, 241, 242 Corn Oil, 41, 241 Cornea, 20, 156, 221, 223, 241, 260, 272, 310 Corneal Transplantation, 20, 241 Coronary, 86, 110, 146, 157, 168, 169, 232, 241, 279, 282 Coronary Artery Bypass, 169, 241 Coronary heart disease, 232, 241 Coronary Thrombosis, 241, 279, 282 Corpus, 241, 275, 296, 312, 320 Corpus Luteum, 241, 275, 296 Cortex, 241, 242, 251, 287, 301 Cortical, 5, 242, 305, 312 Corticosteroid, 5, 17, 67, 155, 156, 158, 159, 161, 162, 242, 296 Corticotropin-Releasing Hormone, 6, 23, 38, 67, 92, 149, 242 Cortisol, 14, 15, 25, 38, 45, 53, 65, 91, 97, 102, 105, 106, 109, 128, 187, 213, 217, 242 Cortisone, 155, 180, 242, 245, 296 Cost-benefit, 101, 242 Cranial, 30, 242, 262, 277, 283, 291, 316, 318, 319
Craniocerebral Trauma, 226, 242, 262, 312, 314 Criterion, 45, 242 Croup, 96, 184, 185, 242 Cryptococcosis, 62, 242 Cryptosporidiosis, 63, 242 Culture Media, 154, 164, 217, 242 Cultured cells, 51, 157, 242 Curative, 63, 152, 242, 312 Curcumin, 69, 242 Cutaneous, 16, 65, 138, 231, 242, 275 Cyclic, 15, 134, 231, 243, 261, 285, 292, 297 Cyclin, 33, 243 Cyclodextrins, 162, 243 Cyclosporine, 29, 243, 266 Cyclosporins, 169, 243 Cyst, 224, 243 Cysteinyl, 243, 279 Cytarabine, 90, 112, 123, 125, 126, 139, 243 Cytochrome, 64, 109, 243 Cytogenetics, 243, 304 Cytokine, 7, 9, 13, 15, 17, 19, 22, 29, 32, 44, 45, 64, 85, 87, 94, 95, 104, 243, 269, 270, 290, 307, 312 Cytomegalovirus, 62, 243 Cytoplasm, 223, 226, 234, 243, 244, 251, 279, 303 Cytoskeleton, 98, 243, 269, 280 Cytostatic, 88, 244 Cytotoxic, 30, 41, 111, 232, 244, 267, 286, 300, 301, 306 Cytotoxic chemotherapy, 244, 286 Cytotoxicity, 62, 218, 236, 244 D Daunorubicin, 90, 97, 125, 244, 247 Deamination, 244, 281, 317 Decarboxylation, 227, 244, 264 Decidua, 20, 244, 293, 315 Decompression, 13, 244 Defense Mechanisms, 11, 244, 269 Defensins, 99, 218, 226, 244 Degenerative, 156, 157, 244, 263, 287 Dehydroepiandrosterone, 114, 132, 162, 244 Deletion, 8, 11, 25, 44, 116, 223, 244 Dementia, 79, 187, 215, 244, 284 Dendrites, 244, 284 Density, 134, 172, 228, 234, 244, 256, 286, 294, 308 Dentate Gyrus, 244, 263 Depolarization, 245, 306 Depressive Disorder, 245, 274
Index 329
Deprivation, 172, 245 Dermatitis, 245, 248 Dermis, 163, 245, 311, 315 Desensitization, 84, 245 Detoxification, 22, 245 Deuterium, 245, 265 Developed Countries, 152, 245 Developing Countries, 152, 245 DEXA, 123, 245 Diabetes Mellitus, 245 Diagnostic procedure, 143, 145, 186, 245 Diaphragm, 144, 245, 302 Diarrhea, 242, 245, 257 Diarrhoea, 245, 258 Diastolic, 245, 265 Diclofenac, 72, 87, 245 Diclofenac Sodium, 245 Diencephalon, 245, 266, 312 Diethylstilbestrol, 73, 246 Digestion, 217, 227, 229, 246, 270, 274, 290, 309 Digestive system, 142, 246, 281 Digestive tract, 232, 246, 307, 308, 309, 321 Dihydrotestosterone, 246, 301, 306 Dilatation, 221, 246, 318 Dilation, 224, 229, 246 Dimethyl, 62, 63, 129, 246 Dimethyl Sulfoxide, 62, 63, 129, 246 Diphenhydramine, 144, 246 Direct, iii, 10, 15, 27, 29, 56, 76, 82, 145, 155, 189, 234, 246, 247, 275, 301, 311 Disease Progression, 53, 246, 319 Disinfectant, 246, 253, 292 Disposition, 24, 42, 86, 109, 246 Dissection, 149, 246 Dissociation, 55, 217, 246, 271 Dissociative Disorders, 246 Distal, 96, 147, 241, 246, 249, 272, 299 Diuresis, 230, 247 Diurnal, 15, 25, 38, 53, 247 Dizziness, 159, 247, 288, 319 DNA Topoisomerase, 247, 259 Docetaxel, 26, 190, 247 Domesticated, 247, 261 Dopamine, 219, 238, 247, 279, 281, 284, 292 Dorsal, 40, 247, 295, 308 Dose-limiting, 59, 247 Double-blind, 55, 67, 90, 96, 97, 99, 101, 102, 104, 114, 166, 247 Double-blinded, 97, 247 Doxorubicin, 66, 72, 92, 94, 100, 102, 113, 120, 122, 125, 126, 127, 128, 129, 247, 251
Drinking Behavior, 50, 247 Drive, ii, vi, 19, 54, 115, 247, 271, 273 Drug Combinations, 176, 247 Drug Delivery Systems, 166, 247 Drug Interactions, 191, 248 Drug Resistance, 8, 26, 248 Drug Tolerance, 248, 314 Duct, 219, 232, 233, 248, 250, 253, 304, 309, 311 Duodenum, 144, 227, 248, 250, 257, 258, 271, 309 Dura mater, 248, 278, 288 Dyskinesia, 237, 248 Dysmenorrhea, 248, 293 Dysplasia, 201, 248 Dystocia, 158, 248 Dystrophy, 200, 248 E Echothiophate Iodide, 156, 248 Ectopic, 27, 31, 248 Eczema, 204, 248 Edema, 173, 248 Effector, 30, 54, 215, 239, 248, 292 Effector cell, 30, 248 Efficacy, 14, 17, 19, 26, 42, 63, 67, 88, 97, 113, 120, 147, 161, 248 Eicosanoids, 9, 20, 248 Ejection fraction, 55, 248 Elastic, 157, 248, 308, 311 Elastin, 157, 238, 249, 254 Elective, 249 Electrocoagulation, 237, 249 Electrode, 77, 164, 165, 249 Electroencephalography, 85, 249 Electrolyte, 46, 217, 242, 249, 260, 280, 295, 307 Elementary Particles, 249, 276, 284, 298 Emaciation, 215, 249 Emboli, 169, 249 Embolus, 249, 267 Embryo, 25, 219, 228, 233, 249, 255, 267, 279, 321 Embryogenesis, 25, 249 Embryology, 25, 249, 255 Emesis, 67, 103, 104, 113, 144, 154, 162, 176, 184, 249, 295 Emetic, 144, 162, 176, 185, 249 Emollient, 249, 260 Emphysema, 236, 249 Emulsion, 111, 158, 159, 249 Encapsulated, 249, 274 Endarterectomy, 221, 224, 250
330
Dexamethasone
Endocarditis, 63, 231, 250 Endocrine Glands, 250 Endocrine System, 53, 250, 284 Endogenous, 11, 22, 23, 29, 39, 40, 56, 226, 228, 247, 248, 250, 315 Endolymphatic Duct, 250 Endolymphatic Sac, 3, 30, 130, 250 Endometrium, 244, 250, 278, 316 Endophthalmitis, 62, 250 Endorphins, 250, 284 Endoscope, 250 Endoscopic, 124, 155, 250 Endosomes, 21, 250 Endothelial cell, 9, 71, 74, 85, 107, 228, 250, 270, 313 Endothelium, 250, 285, 294 Endothelium-derived, 250, 285 Endotoxin, 63, 250, 316 End-stage renal, 236, 250, 294 Energy balance, 27, 250, 273 Enhancer, 28, 65, 251, 302 Enkephalin, 226, 251 Enterocytes, 12, 251 Entorhinal Cortex, 251, 263 Environmental Exposure, 18, 251, 286 Environmental Health, 41, 196, 198, 251 Enzymatic, 22, 219, 227, 231, 239, 251, 264, 278, 303 Eosinophil, 42, 251, 261, 270 Eosinophilic, 17, 83, 251 Epicondylitis, 97, 251 Epidermal, 60, 95, 149, 153, 175, 251, 272, 278, 315, 320 Epidermal Growth Factor, 95, 149, 153, 175, 251, 315 Epidermis, 215, 228, 245, 251, 272, 290, 296, 299 Epidermoid carcinoma, 251, 308, 309 Epidural, 98, 111, 251 Epigastric, 251, 288 Epinephrine, 155, 156, 216, 227, 247, 251, 284, 285, 317 Epirubicin, 70, 120, 130, 251 Epithelial Cells, 48, 52, 75, 86, 98, 99, 105, 151, 226, 251, 252, 263, 272, 280 Epithelium, 12, 25, 29, 57, 104, 105, 169, 226, 250, 251, 252, 257, 271, 289, 315 Epitope, 168, 252 Epoetin alfa, 141, 252 Epoxide Hydrolases, 168, 169, 252 Erythema, 103, 252 Erythema Nodosum, 103, 252
Erythroblasts, 252 Erythrocyte Volume, 228, 252 Erythrocytes, 220, 229, 252, 301 Erythroid Progenitor Cells, 44, 252 Erythromycin, 161, 237, 252 Erythropoietin, 164, 252 Esophageal, 57, 252 Esophagus, 57, 146, 224, 246, 252, 286, 292, 301, 309 Esotropia, 252, 309 Essential Tremor, 200, 253 Estradiol, 4, 33, 169, 170, 253, 306 Estrogen, 4, 40, 158, 237, 253, 297, 305, 311 Estrogen receptor, 237, 253 Ethanol, 25, 162, 237, 253 Etoposide, 66, 70, 91, 119, 120, 122, 123, 126, 128, 129, 139, 253 Eukaryotic Cells, 253, 267, 286, 317 Eustachian tube, 82, 253 Evacuation, 240, 253, 257, 288 Evoke, 253, 309 Excipients, 176, 253, 294 Excitability, 21, 253 Excitation, 56, 253, 255, 284 Exercise Test, 19, 253 Exocrine, 253, 288 Exogenous, 22, 148, 248, 250, 253, 258 Exotropia, 253, 309 Expander, 148, 149, 254 Extender, 254 External-beam radiation, 254, 271, 300 Extracellular, 20, 21, 27, 75, 92, 98, 164, 172, 224, 240, 254, 255, 269, 277, 287, 307 Extracellular Matrix, 20, 75, 92, 98, 240, 254, 255, 269, 277, 287 Extracellular Matrix Proteins, 75, 254, 277 Extracellular Space, 254 Extracorporeal, 175, 254 Extraocular, 160, 254 Extrarenal, 21, 254 Extravasation, 36, 40, 254, 262 Extravascular, 86, 254 Extremity, 254, 289 F Facial, 58, 254, 277 Facial Expression, 58, 254 Family Planning, 197, 254 Fatal Outcome, 254, 300 Fatigue, 56, 103, 141, 236, 254, 262 Fatty acids, 41, 217, 248, 255, 260, 274, 297 Femoral, 232, 255 Femoral Artery, 232, 255
Index 331
Fentanyl, 38, 255 Fetal Blood, 20, 255 Fetal Heart, 94, 255 Fetal Membranes, 20, 255 Fetoprotein, 255 Fetus, 24, 49, 55, 138, 218, 235, 252, 255, 256, 293, 296, 318 Fibrin, 146, 228, 255, 293, 313 Fibrinogen, 255, 293, 313 Fibroblasts, 89, 96, 146, 240, 255, 270 Fibronectins, 254, 255 Fibrosarcoma, 68, 174, 255 Fibrosis, 12, 55, 65, 145, 201, 218, 255, 305 Fistula, 255, 258 Flatulence, 155, 255 Flatus, 255, 257 Flow Cytometry, 20, 255 Floxuridine, 100, 127, 138, 256 Fludarabine, 89, 90, 124, 125, 256 Flumethasone, 158, 256 Fluorescence, 6, 255, 256 Fluorescent Dyes, 255, 256 Fluorouracil, 256 Fluoxymesterone, 185, 256 Flushing, 159, 256 Foetal, 73, 256 Folate, 44, 256 Fold, 221, 256 Folic Acid, 256, 273 Follicles, 56, 256 Foramen, 235, 256, 277, 291 Forearm, 34, 228, 256 Fossa, 30, 256 Free Radicals, 41, 222, 246, 256 Functional Disorders, 38, 257 Functional magnetic resonance imaging, 58, 257 Fungi, 222, 240, 243, 250, 257, 279, 280, 313, 321 Fungistatic, 257, 308 Fungus, 12, 231, 242, 257 G Gadolinium, 13, 257 Gallate, 14, 257 Gallbladder, 215, 227, 235, 246, 257 Gamma irradiation, 35, 257 Gamma Rays, 257, 300 Ganglia, 40, 215, 226, 257, 283, 291 Ganglion, 16, 257, 316, 319 Gas, 10, 74, 168, 219, 232, 255, 257, 265, 277, 285, 302, 311, 318, 319 Gas exchange, 10, 257, 302, 318, 319
Gastric, 15, 90, 123, 144, 154, 219, 251, 257, 264, 290 Gastric Emptying, 154, 257 Gastric Juices, 257, 290 Gastric Mucosa, 123, 257, 290 Gastrin, 258, 264 Gastroduodenal, 124, 258 Gastroenteritis, 15, 258 Gastrointestinal tract, 166, 253, 255, 256, 258, 273, 306, 307, 309 Gelatin, 242, 258, 260, 310, 313 Gelatinase A, 46, 258 Gemcitabine, 66, 120, 138, 258 Gene, 6, 7, 11, 13, 21, 22, 24, 26, 27, 28, 32, 35, 40, 44, 45, 46, 47, 48, 51, 56, 57, 58, 60, 61, 64, 65, 70, 75, 86, 87, 92, 102, 123, 148, 160, 167, 172, 175, 180, 201, 202, 218, 227, 258, 269, 286, 294, 302, 308 Gene Targeting, 6, 258 Gene Therapy, 70, 172, 175, 258 Genetic Code, 258, 285 Genetic Engineering, 227, 237, 258 Genetics, 240, 243, 258 Genistein, 124, 129, 259 Genital, 20, 236, 237, 259 Genotype, 259, 292 Germ Cells, 259, 287, 307, 312, 321 Gestation, 19, 24, 50, 55, 138, 259, 290, 293 Gestational, 55, 69, 259 Gestational Age, 55, 69, 259 Ginseng, 132, 259 Gland, 151, 170, 216, 236, 242, 259, 265, 275, 288, 289, 293, 298, 305, 309, 310, 311, 313 Glioma, 30, 54, 259 Gliosarcoma, 36, 259 Glomerular, 37, 259 Glomerulus, 259, 272 Glucans, 243, 259 Glucose tolerance, 5, 259 Glucose Tolerance Test, 259 Glucuronic Acid, 259, 263 Glutamic Acid, 256, 260, 284, 297 Glutamine, 124, 175, 179, 260 Glutathione Peroxidase, 260, 305 Glycerol, 176, 260, 292 Glycerophospholipids, 260, 292 Glycine, 219, 227, 260, 284, 305 Glycogen, 37, 260 Glycogen Synthase, 37, 260 Glycoprotein, 42, 133, 252, 255, 260, 261, 272, 276, 306, 313, 316
332
Dexamethasone
Glycosaminoglycan, 92, 260 Glycoside, 260, 265, 304 Glycosidic, 164, 260, 286 Glycosylation, 164, 260 Glycyrrhetinic Acid, 116, 260 Goblet Cells, 251, 260 Gonadal, 260, 309 Gonadotropin, 57, 230, 260 Governing Board, 260, 295 Grade, 36, 66, 119, 261 Graft, 169, 243, 261, 264, 267, 280 Graft Rejection, 243, 261, 267, 280 Grafting, 241, 261, 267 Gramicidin, 161, 162, 171, 261 Gram-negative, 261, 286, 295, 314 Gram-positive, 261, 285, 286, 309 Granisetron, 67, 69, 72, 90, 116, 121, 161, 162, 261 Granulocyte, 72, 90, 91, 97, 103, 104, 121, 125, 261, 269 Granulocyte-Macrophage ColonyStimulating Factor, 91, 104, 261 Granulosa Cells, 107, 116, 261, 275 Growth factors, 7, 20, 33, 150, 153, 154, 261, 280 Growth Plate, 93, 261 Guanylate Cyclase, 261, 285 Guinea Pigs, 133, 150, 261 Gynaecological, 102, 262 Gyrase, 262, 285 H Haematemesis, 249, 262 Hair Cells, 29, 262, 277 Hair follicles, 245, 262 Half-Life, 233, 262, 293 Haptens, 217, 262 Headache, 15, 97, 160, 230, 262, 268 Headache Disorders, 262 Heart attack, 146, 232, 262 Heart failure, 48, 262 Helminths, 262, 268 Hematogenous, 83, 262 Hematologic malignancies, 262, 275 Hematoma, 64, 262 Hematopoiesis, 262, 270 Heme, 227, 243, 262 Hemoglobin, 52, 220, 252, 262, 263, 273 Hemoglobinopathies, 258, 263 Hemoglobinuria, 200, 263 Hemorrhage, 242, 249, 262, 263, 299, 310, 311 Hemostasis, 263, 269, 306
Heparin, 146, 263 Hepatic, 12, 22, 24, 28, 100, 127, 138, 168, 169, 175, 217, 256, 259, 263, 274, 281, 291 Hepatitis, 23, 39, 152, 263 Hepatocellular, 129, 263 Hepatocyte, 10, 25, 84, 90, 263 Hepatocyte Growth Factor, 84, 90, 263 Hepatotoxicity, 122, 263 Hereditary, 156, 263, 303 Heredity, 215, 258, 263 Herpes, 61, 63, 148, 152, 263 Herpes Zoster, 152, 263 Heterodimers, 22, 263, 269 Heterogeneity, 217, 263 Heterotropia, 263, 309 Heterozygotes, 5, 263 Hibernation, 230, 263 Hippocampus, 14, 26, 187, 244, 263, 274, 310 Hirsutism, 72, 185, 264, 265 Histamine, 99, 220, 222, 227, 246, 264 Histocompatibility, 152, 264, 280 Histocompatibility Antigens, 152, 264 Histology, 36, 264 Hoarseness, 242, 264 Holocaust, 109, 264 Homeostasis, 21, 167, 175, 264 Homologous, 35, 218, 228, 243, 258, 263, 264, 311 Hormonal, 48, 224, 242, 264 Hormone therapy, 141, 264 Host, 9, 11, 15, 32, 148, 225, 231, 244, 264, 267, 273, 299, 303, 320 Human papillomavirus, 95, 159, 264 Hyaluronidase, 149, 264 Hybrid, 4, 8, 54, 164, 174, 237, 264 Hybridization, 7, 264 Hybridoma, 121, 174, 264 Hydrocortisone, 14, 74, 106, 145, 151, 160, 171, 264 Hydrogen, 95, 129, 215, 219, 226, 232, 245, 254, 260, 264, 265, 274, 280, 284, 285, 287, 298, 312 Hydrogen Peroxide, 95, 129, 260, 265, 274 Hydrolases, 169, 265, 292 Hydrolysis, 236, 265, 271, 290, 292, 298 Hydroxyeicosatetraenoic Acids, 169, 265 Hydroxylation, 231, 265 Hydroxylysine, 238, 265 Hydroxyproline, 219, 238, 265 Hyperalgesia, 40, 265 Hyperandrogenism, 111, 265
Index 333
Hypercalcemia, 59, 265 Hyperplasia, 101, 265 Hypersecretion, 156, 265 Hypersensitivity, 26, 171, 218, 245, 246, 251, 265, 273, 303 Hypertension, 27, 49, 56, 79, 168, 232, 262, 265, 289, 297, 314 Hyperthyroidism, 34, 265, 297 Hypertrichosis, 264, 265 Hypertrophic cardiomyopathy, 91, 265 Hypertrophy, 226, 241, 265, 316 Hypnotic, 226, 246, 266, 312 Hypogonadism, 256, 266 Hypotensive, 83, 266 Hypothalamic, 6, 10, 14, 15, 18, 23, 25, 29, 38, 39, 50, 53, 56, 92, 133, 149, 150, 266, 308 Hypothalamus, 54, 225, 242, 245, 251, 266, 274, 293, 307, 313 Hypoxia, 12, 44, 93, 266, 312 Hysterotomy, 235, 266 I Id, 117, 130, 200, 204, 210, 212, 266 Idiopathic, 103, 104, 107, 266 Ileostomy, 266, 283 Ileum, 46, 266, 271 Imidazole, 228, 264, 266 Imipramine, 24, 266 Immune function, 266, 267 Immune response, 3, 15, 30, 35, 216, 222, 225, 242, 261, 262, 266, 269, 276, 310, 319, 320 Immunity, 11, 215, 244, 266, 276 Immunodeficiency, 152, 200, 215, 266 Immunoglobulin, 95, 221, 266, 269, 281 Immunohistochemistry, 7, 20, 266 Immunologic, 30, 235, 259, 266, 276, 290, 301 Immunology, 28, 73, 74, 88, 91, 99, 120, 121, 174, 216, 217, 256, 266 Immunophilins, 60, 266, 307 Immunosuppressant, 218, 256, 266, 279, 307 Immunosuppressive, 29, 30, 41, 166, 168, 243, 259, 267, 311, 312 Immunosuppressive Agents, 29, 30, 267 Immunotherapy, 227, 245, 267 Impairment, 187, 224, 248, 267, 278 Implant radiation, 267, 270, 271, 300 Implantation, 25, 148, 149, 156, 168, 169, 240, 267, 287 In situ, 16, 28, 30, 40, 50, 267
In Situ Hybridization, 16, 40, 50, 267 Incision, 145, 168, 266, 267, 270 Incontinence, 267, 305 Indicative, 47, 179, 267, 289, 318 Indolent, 89, 123, 124, 267 Indolent lymphoma, 89, 123, 124, 267 Indomethacin, 9, 20, 91, 267, 272 Induction therapy, 126, 137, 267 Infarction, 48, 267 Infection, 9, 11, 19, 23, 32, 61, 62, 65, 67, 77, 85, 103, 147, 166, 185, 215, 224, 225, 227, 231, 235, 236, 242, 243, 252, 258, 261, 266, 267, 268, 275, 282, 284, 285, 286, 290, 300, 303, 309, 310, 313, 320 Infestation, 32, 268 Infiltration, 173, 268, 296 Influenza, 152, 268 Informed Consent, 43, 268 Infuse, 20, 268 Infusion, 20, 127, 138, 146, 148, 158, 159, 166, 229, 256, 268, 315 Ingestion, 18, 34, 165, 230, 259, 268, 294 Inhalation, 190, 217, 268, 294 Initiation, 34, 148, 268, 297, 315 Inlay, 268, 303 Inner ear, 30, 180, 187, 233, 268, 304, 318 Innervation, 16, 48, 268 Inorganic, 236, 268, 281, 285 Inositol, 95, 120, 268 Insecticides, 268, 320 Insight, 4, 8, 27, 31, 33, 44, 46, 268 Insomnia, 173, 268 Insulin, 18, 21, 27, 34, 67, 98, 124, 133, 151, 153, 157, 163, 172, 175, 259, 268, 269, 272 Insulin-dependent diabetes mellitus, 268, 269 Insulin-like, 34, 133, 153, 269 Integrins, 20, 269 Intensive Care, 12, 89, 269 Intensive Care Units, 12, 269 Intercostal, 109, 269 Interferon, 23, 57, 62, 63, 126, 129, 269, 275 Interferon-alpha, 129, 269 Interleukin-1, 29, 62, 64, 79, 96, 107, 149, 269 Interleukin-10, 29, 107, 269 Interleukin-13, 96, 269 Interleukin-2, 62, 269 Interleukin-4, 64, 96, 269 Interleukin-5, 88, 270 Interleukin-6, 11, 49, 64, 67, 70, 101, 270 Interleukin-8, 85, 270
334
Dexamethasone
Interleukins, 164, 267, 270 Intermittent, 270, 275 Internal Medicine, 10, 34, 65, 81, 88, 89, 270, 283 Internal radiation, 270, 271, 300 Interstitial, 229, 254, 258, 270, 271 Interstitial Collagenase, 258, 270 Intestinal, 12, 64, 111, 124, 151, 218, 231, 242, 251, 259, 270, 276, 288, 318, 321 Intestinal Mucosa, 251, 270, 318, 321 Intestine, 46, 151, 227, 229, 238, 270, 272, 291, 299 Intoxication, 270, 320 Intramuscular, 96, 127, 164, 270 Intramuscular injection, 127, 270 Intraocular, 47, 96, 97, 139, 144, 145, 156, 160, 250, 270 Intraocular pressure, 47, 144, 145, 156, 270 Intravascular, 86, 156, 157, 169, 270 Intravenous, 3, 81, 89, 100, 102, 111, 127, 128, 159, 229, 268, 270 Intrinsic, 159, 217, 226, 270 Invasive, 36, 58, 266, 270, 276 Involuntary, 226, 253, 270, 282, 301 Ion Exchange, 234, 270, 271 Ion Transport, 271, 280 Ionization, 74, 271 Ionizing, 218, 251, 271, 300 Ions, 148, 226, 231, 246, 249, 265, 270, 271, 307 Iontophoresis, 87, 271 Irinotecan, 100, 103, 121, 127, 138, 271 Iris, 156, 221, 241, 271, 299, 318 Irradiation, 271 Ischemia, 147, 224, 271 Isotretinoin, 14, 271 Isozymes, 22, 271 J Jejunum, 144, 271 Joint, 40, 45, 55, 84, 224, 236, 271, 287, 311 K Kb, 196, 271 Keratin, 272 Keratinocytes, 60, 270, 272 Keratoconjunctivitis, 107, 272 Ketoacidosis, 215, 272 Ketone Bodies, 215, 272 Ketorolac, 124, 272 Ketorolac Tromethamine, 124, 272 Kidney Cortex, 272, 279 Kidney Disease, 142, 196, 201, 272 Kinetic, 43, 271, 272
L Labile, 239, 272 Labyrinth, 3, 30, 238, 250, 268, 272, 305, 319 Lacrimal, 272, 299 Lacrimal gland, 272, 299 Lactate Dehydrogenase, 125, 272 Lactation, 170, 272, 297 Laminin, 13, 157, 226, 254, 272 Large Intestine, 238, 246, 270, 272, 301, 307 Larynx, 69, 273, 310, 315, 318 Latent, 60, 273, 296 Lectin, 125, 273 Lens, 156, 223, 233, 273 Leptin, 18, 27, 67, 85, 106, 273 Lethal, 11, 38, 48, 225, 273 Leucine, 226, 273, 290 Leucocyte, 218, 251, 273, 275 Leucovorin, 137, 273 Leukaemia, 106, 122, 273 Leukemia, 32, 66, 69, 82, 92, 96, 117, 120, 122, 123, 125, 126, 129, 137, 138, 200, 247, 258, 262, 273, 296 Leukocytes, 20, 42, 62, 226, 229, 235, 267, 269, 270, 273, 316 Leukotrienes, 124, 173, 223, 248, 265, 273 Levobunolol, 155, 273 Libido, 220, 273 Library Services, 210, 273 Lidocaine, 110, 149, 166, 226, 273 Life cycle, 216, 257, 274 Ligament, 274, 298 Ligands, 4, 35, 46, 167, 233, 269, 274 Limbic, 219, 274 Limbic System, 219, 274 Linkage, 29, 51, 274, 290 Lipid, 27, 51, 63, 111, 185, 260, 268, 274, 288, 316 Lipid Peroxidation, 274, 288 Lipophilic, 162, 274 Lipopolysaccharide, 12, 16, 63, 64, 104, 261, 274 Liposomal, 66, 90, 97, 100, 102, 120, 125, 127, 128, 129, 274 Lipoxygenase, 273, 274 Lithium, 10, 97, 274 Litter, 56, 274 Litter Size, 56, 274 Liver cancer, 218, 274 Liver metastases, 138, 274 Liver Regeneration, 25, 274 Localization, 13, 20, 40, 57, 65, 266, 274
Index 335
Localized, 13, 87, 219, 249, 262, 264, 265, 267, 272, 275, 281, 287, 293 Lomustine, 139, 275 Long-Term Care, 13, 275 Loop, 51, 149, 266, 275 Lovastatin, 14, 275 Low-density lipoprotein, 275 Lucida, 272, 275 Lumbar, 23, 84, 275, 308 Lumbar puncture, 23, 275, 308 Lumen, 156, 157, 232, 275 Lupus, 41, 55, 131, 137, 204, 275, 311 Lutein Cells, 275, 297 Lymph, 235, 236, 250, 275, 299, 310 Lymph node, 235, 275, 299 Lymphatic, 220, 250, 268, 275, 279, 307, 308, 313 Lymphatic system, 220, 275, 307, 308, 313 Lymphoblastic, 78, 79, 106, 137, 275 Lymphoblasts, 215, 216, 275 Lymphocyte, 14, 82, 174, 215, 222, 269, 275, 276, 278 Lymphocyte Count, 215, 276 Lymphocytic, 276 Lymphoid, 32, 41, 221, 273, 276 Lymphokines, 276 Lysine, 265, 276, 296 Lyssavirus, 276, 300 M Macroglia, 276, 279 Macrophage, 13, 29, 31, 64, 90, 103, 104, 125, 172, 261, 269, 276 Macrophage Activation, 31, 276 Macrophage Colony-Stimulating Factor, 103, 276 Magnetic Resonance Imaging, 276 Magnetic Resonance Spectroscopy, 10, 276 Maintenance therapy, 137, 276 Major Histocompatibility Complex, 63, 264, 269, 276 Malabsorption, 200, 276 Malformation, 156, 276 Malignancy, 8, 276, 289 Malignant, 30, 37, 43, 51, 156, 174, 200, 215, 216, 222, 256, 274, 276, 277, 281, 283, 287, 300 Malignant tumor, 174, 277, 281, 287 Malnutrition, 217, 224, 230, 277, 282 Mammary, 60, 61, 170, 241, 277, 311 Mandible, 218, 235, 277, 302 Mania, 154, 277
Manic, 228, 274, 277 Manifest, 55, 59, 277, 309 Mannans, 257, 277 Mass Media, 159, 277 Mastectomy, 229, 277 Mastication, 277, 316 Matrix metalloproteinase, 13, 16, 20, 104, 277 Maxillary, 277, 316 Maxillary Nerve, 277, 316 Maximum Tolerated Dose, 43, 248, 277 Measles Virus, 152, 277 Meatus, 277, 317, 318 Mechanoreceptors, 262, 277, 282, 302 Mechlorethamine, 277, 296 Medial, 254, 277, 286, 304 Mediate, 6, 22, 29, 50, 92, 221, 233, 247, 277 Mediator, 15, 169, 269, 277, 306 Medical Staff, 247, 278 MEDLINE, 197, 199, 201, 278 Medullary, 121, 278 Megakaryocytes, 229, 278 Melanin, 271, 278, 292, 317 Melanocytes, 278 Melanoma, 200, 278 Melphalan, 96, 114, 117, 123, 126, 278 Membrane Glycoproteins, 278 Membrane Lipids, 278, 292 Memory, 10, 14, 41, 221, 244, 278 Meninges, 233, 234, 242, 248, 261, 278, 317 Meningitis, 9, 60, 62, 63, 68, 77, 78, 83, 105, 184, 278 Menstrual Cycle, 278, 296 Menstruation, 219, 244, 248, 278, 286 Mental, iv, 4, 87, 142, 196, 198, 202, 234, 235, 244, 246, 254, 277, 278, 299, 304, 317 Mental Disorders, 142, 278, 299 Mental Health, iv, 4, 142, 196, 198, 278, 299 Mental Processes, 246, 278, 299 Mentors, 13, 37, 278 Mercaptopurine, 81, 279 Mercury, 255, 279 Mesenchymal, 7, 157, 163, 251, 261, 276, 279 Mesoderm, 279, 316, 321 Metabolic disorder, 27, 279 Metabolite, 24, 42, 231, 246, 273, 275, 279 Metallothionein, 148, 279 Metastasis, 174, 233, 277, 279 Metastatic, 53, 279, 305 Methazolamide, 156, 279
336
Dexamethasone
Methionine, 226, 246, 279, 310 Methotrexate, 4, 66, 88, 90, 94, 97, 119, 125, 137, 139, 279 Methylprednisolone, 46, 65, 66, 72, 88, 91, 126, 162, 279 Metoclopramide, 67, 68, 72, 98, 116, 121, 144, 176, 279 MI, 48, 62, 75, 108, 129, 168, 214, 279 Microbe, 279, 314 Microbiology, 28, 174, 216, 225, 279 Microglia, 30, 224, 279, 281 Microorganism, 238, 280, 289, 320 Microtubules, 26, 280, 288 Migration, 20, 42, 104, 276, 280 Mineralization, 102, 280 Mineralocorticoid, 54, 280 Minor Histocompatibility Antigens, 264, 280 Miotic, 248, 280, 293 Mitosis, 223, 280, 308 Mitotic, 26, 247, 253, 280, 319 Mitoxantrone, 70, 89, 121, 124, 280 Mobility, 35, 280 Mobilization, 66, 88, 97, 119, 280 Modification, 25, 158, 160, 219, 258, 280, 300 Monitor, 165, 280, 285 Monoamine, 150, 219, 281, 317 Monoamine Oxidase, 150, 219, 281, 317 Monoclonal, 138, 174, 271, 281, 300, 304 Monoclonal antibodies, 138, 174, 281, 304 Monocyte, 63, 276, 281 Mononuclear, 166, 276, 281, 316 Monophosphate, 256, 281 Mood Disorders, 23, 281 Morbillivirus, 277, 281 Morphine, 24, 42, 66, 98, 101, 102, 111, 230, 281, 282, 286 Morphological, 249, 257, 278, 281 Morphology, 37, 233, 276, 281 Motility, 17, 123, 153, 257, 267, 281, 306 Motion Sickness, 79, 281, 283, 305 Mucinous, 257, 281 Mucins, 251, 260, 281, 304 Mucosa, 124, 258, 275, 281, 297, 310 Mucositis, 281, 313 Mucus, 17, 125, 281, 317 Multidose, 147, 281 Multiple Myeloma, 7, 8, 37, 66, 69, 73, 74, 92, 93, 97, 100, 101, 102, 108, 110, 114, 119, 120, 122, 123, 125, 126, 127, 128, 129, 135, 136, 140, 281
Mumps Virus, 152, 282 Muscle Fibers, 282, 316 Muscle relaxant, 221, 282, 292 Muscle Relaxation, 52, 282 Muscle Spindles, 282, 292 Muscular Atrophy, 200, 282 Muscular Dystrophies, 248, 282 Musculoskeletal System, 18, 282 Mutagenic, 151, 218, 282 Myalgia, 173, 268, 282 Mydriatic, 246, 282, 305 Myelodysplastic syndrome, 59, 136, 282, 307 Myelogenous, 282 Myocardial infarction, 48, 91, 226, 241, 279, 282, 297 Myocarditis, 55, 282 Myocardium, 55, 279, 282 Myosin, 282, 316 Myotonic Dystrophy, 200, 282 N Naloxone, 38, 226, 282 Narcotic, 255, 281, 282 Nasal Mucosa, 268, 282 NCI, 1, 76, 136, 137, 138, 139, 140, 141, 142, 195, 236, 283 Nebramycin, 283, 314 Necrotizing Enterocolitis, 124, 283 Need, 3, 17, 24, 36, 145, 147, 152, 161, 163, 167, 173, 180, 186, 205, 217, 236, 260, 277, 283, 314 Neomycin, 159, 161, 283 Neonatal, 18, 19, 55, 61, 64, 68, 73, 84, 90, 94, 99, 106, 116, 137, 283 Neoplasia, 200, 283 Neoplasm, 135, 140, 242, 283, 317 Neoplastic, 33, 163, 264, 276, 283, 299, 304 Nephrology, 37, 283 Nephron, 50, 259, 283 Nephropathy, 272, 283 Nephrotoxic, 283, 295 Nerve Fibers, 16, 283 Nerve Growth Factor, 16, 61, 283, 284 Nervous System, 29, 40, 50, 56, 139, 154, 200, 215, 217, 219, 225, 230, 231, 234, 238, 257, 260, 262, 273, 277, 280, 281, 283, 284, 291, 295, 300, 305, 306, 311, 317, 318 Networks, 27, 33, 39, 283 Neural, 16, 164, 217, 255, 277, 280, 281, 283, 302, 307 Neuralgia, 160, 283
Index 337
Neuroanatomy, 58, 274, 284 Neuroblastoma, 54, 57, 284 Neuroendocrine, 10, 15, 26, 29, 38, 53, 284 Neuroendocrinology, 10, 23, 284 Neuroleptic, 284, 286 Neuromuscular, 215, 284, 295 Neuromuscular Junction, 215, 284 Neuronal, 9, 40, 41, 49, 58, 154, 175, 231, 237, 284 Neurons, 16, 49, 238, 244, 257, 282, 283, 284, 300, 311, 319 Neuropathy, 66, 284 Neuropeptide, 50, 54, 242, 284 Neurosecretory Systems, 250, 284 Neurosyphilis, 284, 289 Neurotoxic, 284, 295 Neurotransmitter, 50, 215, 216, 219, 229, 247, 260, 264, 284, 285, 306, 307, 310, 317, 318 Neurotrophins, 16, 284 Neurovegetative, 23, 284 Neutrons, 218, 271, 284, 300 Neutrophil, 68, 91, 99, 284 Neutrophil Activation, 91, 284 Nitric Oxide, 52, 63, 64, 285 Nitrogen, 52, 218, 219, 220, 243, 254, 260, 278, 285, 316 Nitrogen Oxides, 52, 285 Nocardia, 89, 285, 304 Norepinephrine, 18, 48, 216, 247, 284, 285 Norfloxacin, 176, 285 Nosocomial, 12, 285 Nuclear, 10, 22, 31, 35, 37, 69, 79, 104, 167, 225, 226, 231, 240, 253, 257, 274, 285 Nuclei, 48, 61, 218, 219, 240, 258, 274, 276, 280, 284, 285, 298, 319 Nucleic acid, 21, 47, 150, 258, 264, 267, 285, 299, 300, 303 Nucleic Acid Hybridization, 264, 285 Nucleotidases, 265, 285 O Observational study, 55, 285 Ocular, 94, 124, 144, 145, 155, 156, 160, 252, 253, 286 Oesophagitis, 155, 286 Ofloxacin, 112, 171, 286 Oligomenorrhea, 286, 294 Oligosaccharides, 164, 286 Oncogene, 51, 93, 159, 160, 200, 263, 286 Oncogenic, 269, 286, 298 Oncologist, 286
Ondansetron, 66, 75, 76, 79, 99, 102, 140, 286 Opacity, 233, 244, 286 Ophthalmic, 96, 97, 144, 147, 161, 176, 190, 286, 316 Opiate, 39, 226, 251, 281, 282, 286 Opium, 281, 286 Opportunistic Infections, 215, 286 Optic Chiasm, 266, 286 Organ Culture, 35, 47, 286, 314 Organ Transplantation, 243, 286 Organelles, 234, 237, 243, 278, 286 Osmosis, 287 Osmotic, 139, 217, 287, 306 Osteoarthritis, 45, 287, 293 Osteoblasts, 87, 287 Osteocalcin, 83, 102, 287 Osteoclasts, 76, 287 Osteogenic sarcoma, 287 Osteomyelitis, 73, 287 Osteosarcoma, 102, 287 Otitis, 112, 171, 287 Otitis Media, 112, 287 Otorrhea, 112, 287 Ovarian Follicle, 57, 241, 261, 287 Ovaries, 158, 265, 287, 294, 302, 306 Ovary, 56, 241, 253, 287, 310 Overweight, 117, 155, 287 Ovulation, 57, 221, 237, 261, 287 Ovum, 241, 244, 259, 274, 287, 296, 297, 316, 321 Ovum Implantation, 287, 316 Oxidation, 75, 169, 215, 222, 243, 260, 274, 287, 288 Oxidative metabolism, 273, 288 Oxidative Stress, 41, 288 Oxides, 285, 288 Oxygen Consumption, 253, 288, 302 Oxygenator, 232, 288 Oxytocic, 288, 300 P Pachymeningitis, 278, 288 Paclitaxel, 101, 123, 128, 168, 169, 185, 288 Paediatric, 86, 288 Pain Threshold, 38, 288 Palliative, 110, 130, 288, 312 Palsy, 19, 288 Pancreas, 145, 215, 228, 246, 268, 288, 307 Pancreatic, 5, 200, 251, 288 Pancreatic cancer, 200, 251, 288 Paneth Cells, 218, 251, 288 Panic, 266, 288
338
Dexamethasone
Panic Disorder, 266, 288 Papillomavirus, 64, 289 Paradoxical, 64, 102, 289 Paralysis, 253, 289 Paraparesis, 289 Parasite, 32, 289 Parasitic, 242, 262, 268, 289 Parasympathomimetic, 156, 289 Parathyroid, 231, 289 Parathyroid hormone, 231, 289 Paresis, 173, 289 Paromomycin, 63, 289 Paroxysmal, 200, 262, 289 Partial remission, 105, 289, 302 Partial response, 289 Parturition, 158, 289, 297 Patch, 289, 315 Pathogen, 161, 289 Pathogenesis, 10, 15, 17, 20, 37, 41, 58, 165, 289 Pathologic, 223, 227, 231, 241, 265, 289, 302, 318 Pathologic Processes, 223, 289 Pathophysiology, 18, 20, 51, 52, 290 Patient Selection, 3, 180, 290 Pelvic, 290, 298 Pelvis, 215, 275, 287, 290, 318 Pemphigus, 80, 97, 100, 215, 290 Penicillin, 4, 62, 219, 221, 290 Pentoxifylline, 62, 95, 290 Pepsin, 290 Pepsin A, 290 Peptic, 155, 290 Peptic Ulcer, 155, 290 Peptide, 35, 39, 40, 158, 219, 226, 237, 238, 265, 272, 273, 290, 294, 296, 298, 308 Peptide Chain Elongation, 237, 290 Peptide Fragments, 39, 290 Peptide Hydrolases, 265, 290 Percutaneous, 169, 290, 292 Perforation, 145, 256, 290 Perfusion, 3, 266, 290 Pericardium, 55, 290, 311 Perinatal, 49, 290 Perineal, 89, 290 Perineum, 290, 291 Periodontal disease, 153, 291 Peripheral blood, 122, 166, 269, 291, 296 Peripheral Nervous System, 40, 284, 288, 289, 291, 307, 310, 318 Peristalsis, 144, 291 Peritoneal, 25, 103, 291
Peritoneal Cavity, 25, 291 Peritoneum, 291, 303 Perivascular, 279, 291 Peroxisome Proliferators, 82, 291 Personality Disorders, 81, 291 Petrolatum, 249, 291 Phagocyte, 276, 291 Phagocytosis, 11, 91, 279, 291 Pharmaceutical Solutions, 235, 291 Pharmacodynamics, 43, 291 Pharmacokinetic, 24, 37, 111, 291 Pharmacologic, 24, 220, 225, 262, 291, 300, 314 Pharyngitis, 99, 184, 291 Pharynx, 268, 291, 318 Phenolphthalein, 249, 292 Phenotype, 37, 159, 292 Phenylalanine, 29, 290, 292, 317 Phenylethyl Alcohol, 147, 292 Phenytoin, 81, 89, 232, 292 Phonophoresis, 271, 292 Phorbol, 11, 48, 292 Phosphodiesterase, 290, 292 Phospholipases, 292, 306 Phospholipids, 173, 254, 268, 278, 292 Phosphoric Monoester Hydrolases, 265, 292 Phosphorus, 231, 292 Phosphorylate, 151, 292 Phosphorylated, 47, 238, 292 Phosphorylation, 8, 27, 34, 44, 47, 48, 51, 78, 95, 151, 292, 298 Photocoagulation, 237, 292 Physical Examination, 259, 292 Physiologic, 22, 26, 29, 217, 262, 278, 292, 297, 301, 302, 311, 315 Physiology, 13, 21, 39, 47, 48, 55, 57, 87, 92, 95, 104, 216, 283, 292 Pigmentation, 293, 320 Pilocarpine, 156, 293 Pilot study, 64, 121, 293 Piroxicam, 95, 293 Pituitary Gland, 242, 293 Placenta, 55, 158, 253, 255, 293, 296 Plant Components, 9, 293 Plants, 218, 224, 229, 232, 237, 238, 244, 259, 260, 273, 281, 285, 293, 295, 304, 315, 318 Plaque, 221, 224, 293 Plasma cells, 7, 221, 281, 282, 293 Plasma protein, 217, 293, 306 Plasmid, 148, 293, 318
Index 339
Plasmin, 293 Plasminogen, 164, 174, 293 Plasminogen Activators, 293 Plasticity, 16, 294 Platelet Activation, 294, 306 Platelet Aggregation, 220, 285, 290, 294, 313 Platelet-Derived Growth Factor, 84, 153, 294 Platelets, 226, 285, 294, 313 Platinum, 236, 275, 294 Pneumonia, 240, 294 Podophyllotoxin, 253, 294 Poisoning, 72, 230, 258, 270, 279, 283, 294 Polyarthritis, 9, 294 Polycystic, 114, 201, 265, 294 Polycystic Ovary Syndrome, 114, 265, 294 Polyethylene, 294, 310 Polyethylene Glycols, 294, 310 Polymers, 148, 176, 294, 295, 298 Polymorphism, 7, 65, 84, 295 Polymyxin, 161, 171, 295 Polymyxin B, 171, 295 Polyposis, 238, 295 Polysaccharide, 222, 234, 260, 295, 298 Polyunsaturated fat, 123, 295, 313 Pons, 229, 295 Posterior, 30, 220, 224, 247, 271, 288, 295 Postnatal, 69, 84, 94, 101, 184, 295, 309 Postoperative, 16, 19, 72, 79, 80, 84, 96, 99, 102, 113, 272, 293, 295 Postoperative Nausea and Vomiting, 72, 79, 102, 295 Postsynaptic, 295, 306 Post-translational, 8, 164, 220, 295, 306 Post-traumatic, 44, 45, 58, 262, 295 Post-traumatic stress disorder, 44, 45, 58, 295 Potassium, 21, 217, 280, 295 Potentiates, 37, 59, 60, 70, 269, 295 Potentiation, 101, 128, 295, 306 Practice Guidelines, 198, 295 Precancerous, 235, 296 Preclinical, 14, 59, 296 Precursor, 221, 223, 243, 247, 248, 250, 251, 285, 292, 293, 296, 316, 317 Predisposition, 59, 156, 296 Prednisolone, 68, 83, 106, 145, 155, 160, 279, 296 Prednisone, 30, 55, 68, 81, 112, 121, 129, 137, 296 Pregnancy Tests, 259, 296
Preleukemia, 282, 296, 307 Premedication, 185, 296, 305 Prenatal, 18, 101, 249, 296 Presynaptic, 284, 296 Prevalence, 10, 152, 296 Prickle, 215, 272, 296 Procaine, 152, 274, 296 Procarbazine, 139, 296 Procollagen, 157, 296 Progeny, 175, 240, 296 Progesterone, 116, 167, 170, 296, 297, 309, 318 Progression, 33, 46, 53, 174, 221, 296, 316 Progressive, 13, 135, 170, 171, 233, 236, 244, 248, 261, 282, 287, 294, 297, 317 Progressive disease, 135, 297 Projection, 244, 285, 297, 301 Prolactin, 75, 297 Proline, 238, 265, 296, 297 Promoter, 7, 10, 22, 42, 43, 46, 47, 48, 56, 65, 147, 148, 297 Promotor, 297, 302 Prone, 18, 41, 44, 161, 297 Prophylaxis, 67, 78, 161, 297 Propranolol, 297, 313 Prostaglandin, 20, 116, 165, 169, 237, 297, 313 Prostaglandins A, 173, 267, 297 Prostaglandins D, 297 Prostate, 52, 59, 70, 73, 98, 100, 101, 120, 127, 136, 141, 200, 225, 226, 298 Protease, 238, 298 Protein C, 10, 34, 35, 54, 157, 217, 219, 225, 237, 272, 287, 298, 316, 317 Protein Kinases, 33, 298 Protein S, 4, 34, 102, 180, 201, 228, 237, 252, 258, 283, 287, 298, 303 Protein-Tyrosine Kinase, 259, 298 Proteinuria, 281, 298 Proteoglycan, 87, 157, 298 Proteolytic, 34, 218, 239, 255, 293, 298 Protocol, 43, 66, 119, 120, 296, 298 Protons, 218, 265, 271, 276, 298, 300 Proto-Oncogene Proteins, 288, 298 Proto-Oncogene Proteins c-mos, 288, 298 Protozoa, 240, 280, 298 Protozoan, 234, 242, 298 Proviruses, 60, 298 Proximal, 10, 46, 48, 65, 246, 272, 296, 299 Pruritic, 248, 299 Pruritus, 246, 299 Psychiatric, 6, 10, 34, 39, 91, 278, 299
340
Dexamethasone
Psychiatry, 6, 10, 13, 22, 25, 34, 81, 82, 92, 95, 99, 101, 106, 109, 299, 319 Psychic, 273, 278, 299, 305 Psychoactive, 299, 312, 320 Psychology, 35, 105, 128, 246, 299 Psychomotor, 232, 284, 299 Puberty, 256, 299 Public Health, 10, 17, 155, 198, 299 Public Policy, 197, 299 Pulmonary Artery, 228, 299, 319 Pulmonary Embolism, 146, 299 Pulmonary hypertension, 241, 299 Pulmonary Sarcoidosis, 95, 299 Pulse, 67, 79, 80, 94, 97, 100, 103, 107, 280, 299 Pupil, 241, 246, 280, 282, 299 Purines, 299, 305 Purpura, 91, 95, 103, 104, 107, 183, 299 Purulent, 250, 287, 299, 318 Pylorus, 144, 299 Pyogenic, 287, 299 Pyrimidines, 300, 305 Q Quality of Life, 140, 171, 300 Quaternary, 300, 305 Quiescent, 33, 153, 300 Quipazine, 149, 300 R Rabies, 152, 276, 300 Rabies Virus, 152, 276, 300 Race, 278, 280, 300 Racemic, 278, 300 Radiation oncologist, 43, 286, 300 Radiation therapy, 136, 140, 254, 257, 270, 271, 300, 304 Radioactive, 168, 173, 229, 262, 265, 267, 270, 271, 281, 285, 286, 300 Radiography, 259, 300 Radioimmunotherapy, 300, 301 Radiolabeled, 271, 300 Radiological, 290, 300 Radiotherapy, 185, 229, 271, 300 Raltitrexed, 88, 301 Rape, 295, 301 Reactivation, 60, 90, 301 Reactive Oxygen Species, 79, 301 Receptors, Serotonin, 301, 306 Recombinant, 47, 149, 151, 301, 318 Recombination, 240, 258, 301 Rectal, 138, 301, 310 Rectum, 223, 229, 238, 246, 255, 257, 267, 272, 298, 301, 306
Recurrence, 228, 235, 301 Red blood cells, 252, 301, 304 Red Nucleus, 224, 301 Reductase, 61, 275, 279, 301, 312 Refer, 1, 230, 239, 247, 250, 257, 263, 275, 284, 285, 300, 301, 315, 319 Reflex, 282, 301, 302 Reflux, 144, 155, 301 Refraction, 301, 308 Regeneration, 6, 30, 153, 301 Regimen, 14, 56, 59, 63, 72, 89, 105, 120, 122, 123, 124, 125, 130, 137, 248, 301 Relapse, 10, 43, 302 Relaxin, 158, 302 Remission, 185, 228, 276, 301, 302 Renal cell carcinoma, 88, 302 Renin, 49, 221, 302 Renin-Angiotensin System, 49, 302 Research Support, 34, 302 Resection, 100, 127, 302 Resorption, 12, 231, 287, 302 Respiration, 232, 255, 280, 288, 302 Respiratory distress syndrome, 230, 302 Respiratory Mechanics, 87, 302 Respiratory Physiology, 75, 81, 105, 302, 318 Respiratory syncytial virus, 67, 77, 85, 302 Respiratory System, 302, 318 Response Elements, 28, 56, 167, 302 Response rate, 10, 136, 302 Restitution, 90, 302 Restoration, 6, 13, 21, 22, 301, 302, 303, 320 Retching, 90, 303 Retina, 236, 273, 286, 299, 303, 304, 306, 320 Retinal, 286, 303, 320 Retinoblastoma, 200, 303 Retrograde, 16, 303 Retroperitoneal, 216, 303 Retroviral vector, 60, 258, 303 Retrovirus, 299, 303 Rheology, 290, 303 Rheumatic Diseases, 45, 103, 303 Rheumatism, 303 Rheumatoid, 18, 45, 93, 149, 150, 165, 170, 171, 173, 238, 293, 303 Rheumatoid arthritis, 18, 45, 93, 149, 150, 165, 170, 171, 173, 238, 293, 303 Rhinovirus, 152, 303 Ribonucleic acid, 303 Ribonucleoproteins, 55, 303 Ribosome, 303, 315
Index 341
Risk factor, 27, 44, 45, 304 Ristocetin, 304, 318 Rituximab, 90, 105, 125, 138, 304 Rod, 225, 237, 304 Round Window, 3, 187, 304 Rubulavirus, 282, 304 S Saccule, 29, 304, 319 Saccule and Utricle, 29, 304 Saliva, 300, 304 Salivary, 26, 45, 53, 105, 106, 128, 243, 246, 288, 304, 310 Salivary glands, 243, 246, 304 Salvage Therapy, 112, 304 Saphenous, 241, 304 Saphenous Vein, 241, 304 Saponins, 304, 309 Satellite, 153, 304 Schizoid, 304, 320 Schizophrenia, 35, 154, 304, 320 Schizotypal Personality Disorder, 304, 320 Sclerosis, 200, 238, 305 Scopolamine, 144, 305 Screening, 4, 20, 59, 167, 237, 305 Sebaceous, 245, 305 Sebaceous gland, 245, 305 Secondary tumor, 279, 305 Sedative, 226, 246, 266, 305 Sedimentation, 234, 305, 316 Seizures, 89, 232, 289, 292, 305 Selective estrogen receptor modulator, 305, 311 Selenium, 163, 305 Semen, 298, 305 Semicircular canal, 268, 305 Semisynthetic, 219, 231, 237, 253, 305 Sensibility, 220, 265, 305 Septic, 83, 224, 305 Sequencing, 305, 311 Serine, 33, 78, 150, 164, 298, 305 Serotonin, 6, 13, 149, 227, 237, 261, 281, 284, 286, 300, 301, 306, 316 Serrata, 236, 306 Serum Albumin, 153, 175, 228, 306 Sex Characteristics, 220, 299, 306, 312 Sex Determination, 201, 306 Sex Hormone-Binding Globulin, 106, 306 Shock, 53, 60, 264, 306, 315 Sigmoid, 30, 306 Sigmoid Colon, 306 Signal Transduction, 29, 51, 54, 164, 268, 306
Signs and Symptoms, 165, 302, 306 Sirolimus, 169, 266, 306 Skeletal, 27, 34, 46, 56, 154, 163, 179, 220, 237, 281, 282, 307, 316 Skeleton, 215, 271, 297, 307 Skull, 242, 307, 312 Small intestine, 248, 264, 266, 270, 271, 307 Smoldering leukemia, 282, 307 Social Environment, 300, 307 Social Isolation, 53, 304, 307 Sodium, 16, 21, 97, 145, 152, 164, 176, 217, 245, 280, 307, 311 Sodium Channels, 16, 307 Soft tissue, 229, 255, 307, 314 Soft tissue sarcoma, 255, 307 Solid tumor, 27, 220, 228, 247, 275, 307 Solvent, 162, 215, 246, 253, 260, 287, 291, 307 Soma, 90, 307 Somatic, 38, 249, 274, 280, 291, 307, 318 Somatostatin, 71, 121, 307 Somatotropin, 170, 308 Sorbic Acid, 147, 308 Sound wave, 240, 308, 317 Soybean Oil, 295, 308 Spatial disorientation, 247, 308 Specialist, 205, 246, 308 Specificity, 54, 65, 217, 231, 296, 308 Spectrum, 147, 242, 280, 285, 308 Sperm, 220, 236, 308, 316 Spinal cord, 40, 224, 229, 234, 235, 248, 251, 257, 278, 283, 284, 288, 289, 291, 301, 308 Spinal Nerves, 291, 308 Spinal tap, 275, 308 Spinous, 251, 272, 308 Spleen, 174, 219, 243, 264, 275, 308 Sporadic, 303, 308 Squamous, 57, 59, 95, 251, 308, 309 Squamous cell carcinoma, 59, 95, 251, 308 Squamous cells, 308, 309 Stabilization, 19, 292, 309 Stasis, 15, 155, 309 Staurosporine, 56, 309 Steel, 237, 309 Stellate, 22, 309 Stem cell transplantation, 90, 91, 126, 309 Stem Cells, 6, 25, 163, 175, 252, 309 Stenosis, 146, 150, 167, 168, 309, 310 Stent, 146, 156, 157, 168, 309 Sterility, 114, 243, 309
342
Dexamethasone
Steroid, 19, 36, 40, 56, 68, 76, 112, 137, 141, 144, 145, 147, 148, 162, 164, 166, 167, 171, 173, 176, 181, 187, 227, 242, 256, 304, 309 Stimulant, 219, 230, 264, 309 Stimulus, 38, 149, 240, 247, 248, 249, 253, 268, 270, 301, 309, 313 Stool, 238, 267, 273, 309 Strabismus, 72, 309 Streptococcal, 149, 309 Streptococcus, 62, 309 Stricture, 309, 310 Stridor, 242, 310 Stroke, 142, 146, 196, 232, 310 Stroma, 271, 310 Stromal, 31, 75, 86, 229, 310 Stromal Cells, 86, 229, 310 Subacute, 268, 310 Subarachnoid, 9, 262, 310 Subclinical, 55, 267, 305, 310 Subcutaneous, 9, 110, 148, 149, 185, 216, 248, 310 Subiculum, 263, 310 Submaxillary, 251, 310 Subspecies, 308, 310 Substance P, 252, 279, 304, 305, 310 Substrate, 28, 42, 165, 172, 265, 310, 317 Sulfur, 254, 279, 310 Supplementation, 41, 124, 128, 310 Suppository, 176, 294, 310 Suppression, 5, 13, 17, 25, 45, 46, 49, 53, 54, 57, 67, 69, 81, 83, 85, 88, 89, 93, 95, 97, 98, 99, 100, 101, 103, 109, 110, 111, 113, 134, 160, 165, 213, 242, 310 Suppressive, 54, 310 Surfactant, 10, 48, 176, 311 Suspensions, 176, 311 Sweat, 245, 311 Sweat Glands, 245, 311 Sympathomimetic, 219, 247, 251, 285, 311, 317 Symphysis, 235, 298, 311 Synapse, 216, 284, 296, 311, 315 Synaptic, 284, 306, 311 Synchrony, 38, 311 Synergistic, 90, 107, 129, 176, 297, 311 Synovial, 40, 104, 311 Systemic disease, 160, 311 Systemic lupus erythematosus, 41, 55, 238, 311 Systolic, 265, 311
T Tacrolimus, 168, 169, 266, 311 Tamoxifen, 69, 305, 311 Tamponade, 91, 311 Tardive, 237, 311 Telangiectasia, 201, 311 Temporal, 19, 30, 219, 262, 263, 277, 312 Temporal Lobe, 219, 312 Tendon, 257, 312 Teratogenic, 218, 271, 312 Terbutaline, 184, 312 Testis, 220, 253, 312 Testosterone, 5, 162, 301, 306, 312 Tetrahydrocannabinol, 232, 312 Thalamic, 224, 312 Thalamic Diseases, 224, 312 Thalidomide, 7, 71, 73, 74, 92, 108, 113, 114, 140, 312 Therapeutics, 4, 55, 73, 88, 90, 94, 136, 144, 191, 281, 312 Thermal, 246, 284, 312 Thiamphenicol, 44, 312 Thimerosal, 147, 312 Thioredoxin, 129, 312 Thiotepa, 66, 120, 312 Third Ventricle, 266, 312 Thoracic, 245, 313, 320 Thorax, 77, 215, 275, 313, 318 Threonine, 33, 150, 164, 298, 305, 313 Threshold, 253, 265, 313 Thrombin, 255, 294, 298, 313 Thrombolytic, 293, 313 Thrombomodulin, 298, 313 Thrombosis, 74, 146, 226, 269, 298, 310, 313 Thromboxanes, 223, 248, 265, 313 Thrombus, 146, 241, 267, 294, 313 Thrush, 231, 313 Thymidine, 148, 313 Thymidine Kinase, 148, 313 Thymus, 11, 31, 35, 275, 313 Thyroid, 10, 21, 34, 48, 53, 265, 289, 313, 317 Thyroid Gland, 265, 289, 313 Thyroxine, 217, 292, 313 Ticks, 268, 313 Timolol, 155, 156, 313 Tinnitus, 287, 313 Tissue Culture, 29, 153, 314 Tissue Expansion, 148, 149, 314 Tissue Transplantation, 163, 314 Tobramycin, 147, 161, 190, 314
Index 343
Tolerance, 9, 216, 230, 259, 314 Tone, 144, 314 Tonic, 19, 314 Tonicity, 176, 314 Tonus, 314 Topical, 14, 96, 110, 112, 147, 156, 161, 171, 176, 190, 235, 246, 253, 265, 271, 291, 312, 314 Topoisomerase inhibitors, 271, 314 Topotecan, 66, 88, 120, 314 Torsion, 267, 314 Toxicity, 14, 17, 37, 43, 59, 82, 112, 123, 128, 160, 166, 185, 232, 248, 277, 279, 304, 314 Toxicology, 198, 314 Toxin, 250, 314, 315 Trabecular Meshwork, 47, 70, 71, 96, 98, 109, 156, 315 Trace element, 151, 229, 236, 315 Trachea, 146, 229, 230, 273, 292, 310, 313, 315 Traction, 237, 315 Transcription Factors, 8, 25, 27, 48, 56, 60, 302, 315 Transdermal, 112, 166, 315 Transduction, 35, 54, 69, 306, 315 Transfection, 46, 51, 64, 227, 258, 315 Transferases, 22, 260, 315 Transforming Growth Factor alpha, 153, 315 Transfusion, 88, 97, 254, 315 Translation, 34, 51, 219, 252, 283, 315 Translational, 315 Translocation, 9, 78, 91, 104, 237, 252, 315 Transmitter, 215, 224, 247, 278, 285, 315, 317 Transplantation, 6, 107, 126, 163, 236, 264, 276, 315 Trauma, 12, 13, 30, 44, 147, 157, 168, 314, 315 Tremor, 313, 315 Tricuspid Atresia, 241, 316 Tricyclic, 237, 266, 300, 316 Trigeminal, 16, 160, 277, 316 Trigeminal Nerve, 16, 316 Triglyceride, 159, 316 Trophoblast, 16, 228, 316 Tropomyosin, 316 Troponin, 80, 316 Tryptophan, 238, 306, 316 Tuberous Sclerosis, 201, 316 Tubulin, 280, 316
Tumor model, 36, 316 Tumor Necrosis Factor, 23, 57, 60, 62, 64, 75, 98, 104, 312, 316 Tumor suppressor gene, 159, 160, 316 Tumour, 105, 151, 257, 317 Tunica, 250, 281, 317 Tympanic membrane, 171, 317 Tyramine, 227, 281, 317 Tyrosine, 37, 151, 247, 298, 317 Tyrothricin, 261, 317 U Ubiquitin, 34, 317 Ulcerative colitis, 67, 79, 317 Ultrasonography, 259, 317 Ultrasound test, 138, 317 Unconscious, 220, 244, 266, 317 Unresectable, 127, 317 Urea, 311, 317 Uremia, 21, 317 Ureters, 317 Urethra, 225, 226, 298, 317 Urinary, 146, 233, 236, 267, 285, 305, 317, 320 Urinary tract, 146, 233, 317 Urine, 18, 74, 225, 226, 228, 247, 251, 263, 267, 272, 285, 298, 317 Uteroglobin, 173, 318 Uterus, 235, 241, 244, 250, 266, 278, 287, 288, 296, 311, 318 Uvea, 250, 318 Uveal tract, 299, 318 V Vaccine, 152, 216, 298, 318 Vagina, 231, 235, 246, 266, 278, 311, 318 Vaginal, 310, 318 Vaginitis, 231, 318 Vagus Nerve, 41, 318 Vancomycin, 62, 63, 318 Vasoactive, 49, 52, 318 Vasoactive Intestinal Peptide, 49, 52, 318 Vasoconstriction, 251, 318 Vasodilators, 285, 318 VE, 109, 318 Vector, 148, 159, 163, 164, 315, 318 Vegetative, 284, 318 Vein, 74, 270, 285, 304, 318 Venous, 89, 226, 298, 316, 318 Venous blood, 89, 318 Ventilation, 187, 230, 302, 318 Ventricle, 219, 224, 241, 263, 299, 311, 313, 316, 319 Ventricular, 48, 55, 241, 248, 311, 316, 319
344
Dexamethasone
Ventricular Dysfunction, 248, 319 Venules, 228, 319 Verapamil, 112, 319 Vertebrae, 308, 319 Vertigo, 287, 319 Vesicular, 261, 263, 319 Vestibular, 29, 180, 187, 262, 319 Vestibule, 238, 268, 304, 305, 319 Vestibulocochlear Nerve, 304, 314, 319 Veterinary Medicine, 116, 154, 197, 319 Vial, 62, 319 Vinblastine, 66, 119, 316, 319 Vinca Alkaloids, 319 Vinorelbine, 66, 120, 319 Viral, 47, 85, 152, 160, 173, 187, 255, 268, 286, 300, 303, 315, 319, 320 Viral Load, 85, 319 Viral vector, 47, 319 Virilism, 265, 320 Virulence, 314, 320 Visceral, 37, 38, 225, 274, 291, 318, 320 Visceral Afferents, 225, 318, 320 Viscosity, 147, 264, 303, 320 Vitamin A, 268, 320 Vitreoretinal, 96, 320 Vitreous, 273, 303, 320 Vitro, 8, 9, 11, 12, 13, 17, 21, 23, 29, 37, 42, 43, 47, 48, 49, 59, 67, 68, 82, 86, 87, 94,
102, 107, 116, 151, 153, 154, 163, 166, 174, 233, 258, 263, 267, 304, 311, 314, 320 Vivo, 9, 11, 12, 13, 17, 23, 26, 29, 31, 35, 37, 41, 42, 43, 44, 46, 47, 48, 49, 50, 57, 59, 88, 94, 125, 130, 174, 258, 263, 267, 311, 313, 320 Voltage-gated, 56, 320 W War, 89, 125, 240, 264, 277, 295, 320 Warts, 264, 294, 320 Water Deprivation, 50, 320 White blood cell, 215, 216, 221, 236, 261, 273, 275, 276, 281, 282, 284, 293, 320 Windpipe, 230, 292, 313, 320 Withdrawal, 25, 320 Wound Healing, 20, 147, 233, 269, 277, 320 X Xanthine, 62, 320 Xenobiotics, 28, 320 Xenograft, 105, 221, 316, 320 X-ray, 245, 256, 257, 271, 285, 300, 321 Y Yeasts, 231, 257, 292, 321 Yolk Sac, 255, 321 Z Zoonoses, 300, 321 Zygote, 240, 321 Zymogen, 298, 321
