GLUTATHIONE A M EDICAL D ICTIONARY , B IBLIOGRAPHY , AND A NNOTATED R ESEARCH G UIDE TO I NTERNET R E FERENCES
J AMES N. P ARKER , M.D. AND P HILIP M. P ARKER , P H .D., E DITORS
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ICON Health Publications ICON Group International, Inc. 4370 La Jolla Village Drive, 4th Floor San Diego, CA 92122 USA Copyright 2004 by ICON Group International, Inc. Copyright 2004 by ICON Group International, Inc. All rights reserved. This book is protected by copyright. No part of it may be reproduced, stored in a retrieval system, or transmitted in any form or by any means, electronic, mechanical, photocopying, recording, or otherwise, without written permission from the publisher. Printed in the United States of America. Last digit indicates print number: 10 9 8 7 6 4 5 3 2 1
Publisher, Health Care: Philip Parker, Ph.D. Editor(s): James Parker, M.D., Philip Parker, Ph.D. Publisher's note: The ideas, procedures, and suggestions contained in this book are not intended for the diagnosis or treatment of a health problem. As new medical or scientific information becomes available from academic and clinical research, recommended treatments and drug therapies may undergo changes. The authors, editors, and publisher have attempted to make the information in this book up to date and accurate in accord with accepted standards at the time of publication. The authors, editors, and publisher are not responsible for errors or omissions or for consequences from application of the book, and make no warranty, expressed or implied, in regard to the contents of this book. Any practice described in this book should be applied by the reader in accordance with professional standards of care used in regard to the unique circumstances that may apply in each situation. The reader is advised to always check product information (package inserts) for changes and new information regarding dosage and contraindications before prescribing any drug or pharmacological product. Caution is especially urged when using new or infrequently ordered drugs, herbal remedies, vitamins and supplements, alternative therapies, complementary therapies and medicines, and integrative medical treatments. Cataloging-in-Publication Data Parker, James N., 1961Parker, Philip M., 1960Glutathione: 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: 0-597-83962-X 1. Glutathione-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 glutathione. 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 GLUTATHIONE .......................................................................................... 3 Overview........................................................................................................................................ 3 The Combined Health Information Database................................................................................. 3 Federally Funded Research on Glutathione ................................................................................... 4 E-Journals: PubMed Central ....................................................................................................... 63 The National Library of Medicine: PubMed ................................................................................ 79 CHAPTER 2. NUTRITION AND GLUTATHIONE .............................................................................. 121 Overview.................................................................................................................................... 121 Finding Nutrition Studies on Glutathione ................................................................................ 121 Federal Resources on Nutrition ................................................................................................. 126 Additional Web Resources ......................................................................................................... 127 CHAPTER 3. ALTERNATIVE MEDICINE AND GLUTATHIONE ........................................................ 129 Overview.................................................................................................................................... 129 National Center for Complementary and Alternative Medicine................................................ 129 Additional Web Resources ......................................................................................................... 136 General References ..................................................................................................................... 143 CHAPTER 4. DISSERTATIONS ON GLUTATHIONE .......................................................................... 145 Overview.................................................................................................................................... 145 Dissertations on Glutathione ..................................................................................................... 145 Keeping Current ........................................................................................................................ 148 CHAPTER 5. PATENTS ON GLUTATHIONE..................................................................................... 149 Overview.................................................................................................................................... 149 Patents on Glutathione .............................................................................................................. 149 Patent Applications on Glutathione .......................................................................................... 175 Keeping Current ........................................................................................................................ 210 CHAPTER 6. BOOKS ON GLUTATHIONE ........................................................................................ 211 Overview.................................................................................................................................... 211 Book Summaries: Online Booksellers......................................................................................... 211 The National Library of Medicine Book Index ........................................................................... 213 Chapters on Glutathione ............................................................................................................ 214 CHAPTER 7. PERIODICALS AND NEWS ON GLUTATHIONE .......................................................... 217 Overview.................................................................................................................................... 217 News Services and Press Releases.............................................................................................. 217 Academic Periodicals covering Glutathione............................................................................... 219 APPENDIX A. PHYSICIAN RESOURCES .......................................................................................... 223 Overview.................................................................................................................................... 223 NIH Guidelines.......................................................................................................................... 223 NIH Databases........................................................................................................................... 225 Other Commercial Databases..................................................................................................... 228 The Genome Project and Glutathione ........................................................................................ 228 APPENDIX B. PATIENT RESOURCES ............................................................................................... 233 Overview.................................................................................................................................... 233 Patient Guideline Sources.......................................................................................................... 233 Finding Associations.................................................................................................................. 235 APPENDIX C. FINDING MEDICAL LIBRARIES ................................................................................ 237 Overview.................................................................................................................................... 237 Preparation................................................................................................................................. 237 Finding a Local Medical Library................................................................................................ 237 Medical Libraries in the U.S. and Canada ................................................................................. 237
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ONLINE GLOSSARIES................................................................................................................ 243 Online Dictionary Directories ................................................................................................... 243 GLUTATHIONE DICTIONARY ................................................................................................ 245 INDEX .............................................................................................................................................. 347
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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 glutathione 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 glutathione, 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 glutathione, 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 glutathione. 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 glutathione, 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 glutathione. The Editors
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From the NIH, National Cancer Institute (NCI): http://www.cancer.gov/cancerinfo/ten-things-to-know.
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CHAPTER 1. STUDIES ON GLUTATHIONE Overview In this chapter, we will show you how to locate peer-reviewed references and studies on glutathione.
The Combined Health Information Database The Combined Health Information Database summarizes studies across numerous federal agencies. To limit your investigation to research studies and glutathione, 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 “glutathione” (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: •
Liver Disease in Pediatric Patients with Cystic Fibrosis is Associated with Glutathione S-Transferase P1 Polymorphism Source: Hepatology. 36(4 Part 1): 913-917. October 2002. Contact: Available from W.B. Saunders Company. 6277 Sea Harbor Drive, Orlando, FL 19106-3399. (800) 654-2452 or (407) 345-4000. Summary: Liver disease in patients with cystic fibrosis (CF) is inconstant and has not yet been clearly related to any specific risk factor. Among liver detoxifying enzymes, the glutathione S-transferases (GSTs) play a key role in the protection against oxidative stress. This article reports on a study that provides the first demonstration of a significant association between GST gene polymorphism and the development of liver disease in patients with CF. The authors hypothesize that the major role of GSTs as
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detoxifying enzymes is probably emphasized in CF disease by the frequent use of antibiotics and other drugs in these patients. Identification of GSTP1 polymorphism may have prognostic significant in pediatric patients with CF and may direct more targeted therapy toward children with an increased risk of liver disease. 3 tables. 25 references.
Federally Funded Research on Glutathione The U.S. Government supports a variety of research studies relating to glutathione. 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 glutathione. 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 glutathione. The following is typical of the type of information found when searching the CRISP database for glutathione: •
Project Title: A NOVEL CANCER MODEL--VACCINE ASSOCIATED SARCOMA Principal Investigator & Institution: Mcniel, Elizabeth A.; Environmental & Radiological Health Sciences; Colorado State University Fort Collins, Co 80523 Timing: Fiscal Year 2001; Project Start 01-APR-2001; Project End 31-MAR-2002 Summary: (Applicant's Description): Epidemiologic evidence strongly associates vaccination of cats for rabies and feline leukemia virus with the d e v elopment of soft tissue sarcomas at the vaccine site. Genetic susceptibility, sensitivity to reactive oxygen species (ROS), and chronic low dose environmental exposure to metals may all be significant in the development of this carcinogenesis, as well as in the pathogenesis of human cancer. I propose to carry out studies of vaccine induced tumor genetics and the oxidative status of cats as a potentially informative animal model for solid tumor carcinogenesis. Causative chromosome rearrangement have been i d entified in different human tumors; thus, I will employ classical cytogenetic and such molecular cytogenetic techniques as comparative genomic hybridization (CGH) and Multiplex fluorescence in situ hybridization (M-FISH) t o identify recurrent chromosomal aberrations in feline tumors with significance to carcinogenesis. I am adapting these cytogenetic techniques, designed for human tumors, for use in cats. Sensitivity to ROS in cats with and without vaccine induced tumors will be measured with: 1 ) Blood levels of the antioxidant glutathione in conjunction with indicators of oxidant exposure, oxidized glutathione and malondialdehyde, a product of lipid peroxidation. 2) Oxidative DNA base damage, 8-oxoguanine in particular, quantified by spectrometry of DNA from hydrogen peroxide exposed cat fibroblasts. All of these technologies are in place. Development of pet
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Healthcare projects are funded by the National Institutes of Health (NIH), Substance Abuse and Mental Health Services (SAMHSA), Health Resources and Services Administration (HRSA), Food and Drug Administration (FDA), Centers for Disease Control and Prevention (CDCP), Agency for Healthcare Research and Quality (AHRQ), and Office of Assistant Secretary of Health (OASH).
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animal cancer models requires clinical expertise in spontaneous animal tumors combined with laboratory knowledge and skills. I am a veterinary oncologist with abundant clinical experience, currently pursuing a Ph D. I am dedicated to a career in translational cancer research. The Comparative Oncology unit at Colorado State University of which I am a part is dedicated to the development of spontaneous animal tumor models for human cancer and has contributed through the development of experimental therapeutics. I intend to apply the techniques and data acquired from this work to establish a center for animal tumor cytogenetics and genomic to study the role of genetics in the pathogenesis of cancer. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •
Project Title: ACUTE LUNG INJURY--ALCOHOLISM AND GLUTATHIONE DEPLETION Principal Investigator & Institution: Guidot, David M.; Associate Professor of Medicine; Internal Medicine; Emory University 1784 North Decatur Road Atlanta, Ga 30322 Timing: Fiscal Year 2001; Project Start 01-APR-1999; Project End 31-MAR-2003 Summary: The Acute Respiratory Distress Syndrome (ARDS) is a common and severe form of lung injury with a mortality of approximately 50 percent. A prospective study of 351 critically ill patients recently identified that a history of chronic alcohol abuse increased the incidence and severity of ARDS regardless of the at-risk diagnosis. This observation distinguishes chronic alcohol abuse as the first reported co-morbid variable that significantly increases a patient's risk of developing ARDS and raises questions about the pathophysiology and specific treatment of acute lung injury. This project will test the hypothesis that chronic alcohol abuse decreases alveolar type II cell levels of glutathione, an important antioxidant, thereby impairing surfactant secretion and function and rendering the lung susceptible to injury. In ARDS the alveolar type II cells are severely damaged, and their ability to secrete glutathione and surfactant into the alveolar lining fluid are critical to patient survival. Because sepsis is the most common risk factor for ARDS, this project will focus on the sepsis syndrome in both patients and in an animal model. Preliminary studies presented in this proposal show that chronic alcohol ingestion in rats decreases type II cell glutathione levels and, in parallel, decreases type II cell surfactant secretion both in vitro and in vivo, and predisposes to endotoxin-mediated acute lung injury. In addition, we determined that otherwise healthy alcoholics have markedly decreased levels of glutathione in their lung lavage fluid compared to control subjects. The fundamental mechanisms by which chronic alcohol use affects alveolar epithelial function will be examined in a rat model of sepsis in vivo and in isolated type II cells in vitro. Parallel clinical studies in both healthy subjects and in critically ill patients with sepsis will examine the effects of chronic alcohol abuse on lung glutathione homeostasis and surfactant production both in isolated type II cells and in lung lavage fluid. We will thereby test the clinical relevance of the fundamental mechanisms elucidated in the animal model. Importantly, our preliminary studies indicate that glutathione replacement can decrease ethanolmediated lung injury in our animal model, and this project will ultimately focus on developing a glutathione replacement regimen that reduces the harmful effects of chronic alcohol ingestion on the lungs of patients. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen
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Project Title: ADAPT NEURODEGENERATION
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Principal Investigator & Institution: Davies, Kelvin J.; Gerontology; University of Southern California 2250 Alcazar Street, Csc-219 Los Angeles, Ca 90033 Timing: Fiscal Year 2001; Project Start 01-FEB-2000; Project End 31-JAN-2005 Summary: We are interested in a possible link between oxidative stress, aging and neurodegenerative diseases. In recent studies of adaptation to oxidative stress we have identified several previously unknown genes (in addition to confirming the overexpression of several known genes) that appear to provide stress protection in isolated hamster cells in culture. These "adapt" genes include: adapt15, adapt33, adapt66, adapt73, adapt78, and adapt 116. Although our studies indicate that full adaptation depends upon both transcription and translation, it is not clear which genes are actually required. Although each of these newly discovered genes is worthy of detailed study, adapt78 whose mRNA levels increase more than 50 fold in adaptation, in particular stands out. In screening studies employing autopsy samples from human brains, we have now found that the human homologue of adapt78 exhibits extremely high levels of expression in brain autopsy samples from Alzheimer's disease patients, and low levels of expression in brain samples encompassing the substantia nigra from patients who died with Parkinson's disease. Recently, it has become clear that our adapt78 is identical to (or at least highly homologous with) the simultaneously independently discovered Down syndrome critical region 1 (DSCR1) gene of chromosome 21. Furthermore, two different isoforms of both adapt78 and DSCR1 are differentially expressed; corresponding to differentially spliced forms of exons 1-5, 6, 7 and exons 4-5, 6, 7. We propose to now carefully study expression of both isoforms of the human adapt78 gene in different brain regions, using the more sensitive techniques of RT-PCR and in situ hybridization. We plan to study adapt78 expression as a function of age, in brain autopsy samples from otherwise healthy individuals, since adapt78 expression may well vary with age. We will perform detailed studies of brain samples from Alzheimer's disease patients, Parkinson's disease patients, and Down syndrome patients in order to carefully determine both qualitative and quantitative differences in expression of both isoforms of adapt78 mRNA. Localization of adapt78 mRNA expression by cell type will also be studied. We also will synthesize and characterize the (1-5, 6, 7 and 4-5, 6, 7) Adapt78 proteins and generate antibodies to them in order to study expression of the actual proteins in all cell and brain samples. In cell culture studies, with PC-12 cells, we will test the hypothesis that inducible overexpression of adapt78 may confer an oxidative stress resistance phenotype. We will also test the ability of inducible adapt78 overexpressing cells to overcome the lethal oxidizing effects of glutathione deficiency, caused by expression of antisense message to gamma glutamylcysteine synthetase. These studies will allow us to begin to investigate our hypothesis that aging, and perhaps certain neurodegenerative diseases, involving defects in the expression of adapt78 and other adaptive genes required to cope with the deleterious effects of oxidative stress. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •
Project Title: AGE-DEPENDENT ATTENUATION OF ANTIOXIDANT RESPONSES Principal Investigator & Institution: Falkner, Keith C.; Biochem and Molecular Biology; University of Louisville University of Louisville Louisville, Ky 40292 Timing: Fiscal Year 2002; Project Start 01-FEB-2002; Project End 31-JAN-2004
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Summary: Our hypothesis is that there is an age-dependent attenuation of signaling through anti-oxidant or electrophile response elements (A/EpREs). The anti-oxidant response is a transcriptional response that involves binding of transcription factors, Nrf2 and a small maf to the A/EpRE. This element is important for both the basal and inducible expression of enzymes involved in glutathione synthesis, oxidative stress responses and detoxication of xenobiotic compounds. Aging and senescence is known to be characterized by glutathione deficiency and an inability to maintain intracellular glutathione in response to environmental challenge. Compounds that reduce glutathione levels are more toxic in aged animals relative to young animals. A diminished response to environmental stress renders the organism more susceptible to cellular damage or disease leading to death. We believe that these age-related increases in toxicity are due to an inability of the animal to respond to environmental stress caused by attenuation of signaling through A/EpREs. To test my hypothesis I propose the following aims. Specific aim 1. We will test the hypothesis that the reduced ability of aged animals to maintain glutathione levels in response to environmental stress is associated with a reduced level and induction of - glutamylcysteine synthetase activity. Specific Aim 2. We will test the hypothesis that in aged animals, genes whose expression is controlled by A/EpRE show a diminished response to a prototypical A/EpRE inducer, t-butyl hydroxyanisole. Specific Aim 3. We will test the hypothesis that the agerelated attenuation of responses from A/EpRE elements is related to a reduction or alteration of transcription factor binding to A/EpRE elements. The goal of this proposal is to obtain preliminary data to demonstrate the effects of aging on this key signaling pathway in response to environmental challenge. The long term goal of the project is to define age-dependent repressors of detoxification of toxic chemicals. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •
Project Title: AGING AND LEYDIG CELL FUNCTION Principal Investigator & Institution: Zirkin, Barry R.; Professor; Biochem and Molecular Biology; Johns Hopkins University 3400 N Charles St Baltimore, Md 21218 Timing: Fiscal Year 2002; Project Start 01-SEP-2002; Project End 31-AUG-2006 Summary: (provided by applicant): The maximal capacity of Brown Norway rat Leydig cells to produce testosterone decreases significantly with age. Our major objective is to elucidate the molecular mechanisms that are responsible. A central hypothesis of this application is that reactive oxygen species (ROS), produced by the Leydig cells themselves, play an important role in age-related reductions in Leydig cell testosterone production. Three specific aims are proposed. The first is to determine whether agerelated reductions in Leydig cell testosterone production are reversed by administering LH directly to the testes of old rats, or by encapsulating old cells and implanting them into young rats. These studies will test the hypothesis that factors outside the Leydig cells might be responsible for the reduced ability of old Leydig cells to produce testosterone. In the second specific aim, we will determine whether the increases in Leydig cell reactive oxygen production that occur as these cells age are from the mitochondrial transport chain, the P450 reactions of steroidogenesis, or both; and whether there are age-related changes in mRNA, protein, and/or activity levels of the major enzymatic scavengers of reactive oxygen species in Leydig cells - SOD, glutathione peroxidase and catalase. The third aim is to examine the effects of manipulating reactive oxygen load on Leydig cell steroidogenesis during aging, based on the hypothesis that reactive oxygen, whether derived from the electron transport chain, steroidogenesis, or both, plays an important role in the reduced testosterone produced by aging Leydig cells. We will test this hypothesis by examining the
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consequences of manipulating oxidative stress load in vivo on Leydig cell function, including: the effects of vitamin E supplementation and deprivation; the effects of age on the acute response of Leydig cells to depletion of its major non-enzymatic antioxidant, glutathione; and the effects of caloric restriction. Together, these studies will provide new insights into how Leydig cells cope with stressors that are present or increase during aging, and will shed light on the underlying molecular basis for functional changes in Leydig cells that occur during aging. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •
Project Title: ALCOHOL, GLUTATHIONE, AND ALVEOLAR MACROPHAGE FUNCTION Principal Investigator & Institution: Burnham, Ellen L.; Internal Medicine; Emory University 1784 North Decatur Road Atlanta, Ga 30322 Timing: Fiscal Year 2003; Project Start 01-APR-2003; Project End 31-MAR-2008 Summary: (provided by applicant): Each year in the United States, there are an estimated 4 million cases of pneumonia, accounting for 600,000 hospitalizations with an annual cost of $23 billion. Alcohol is a common risk factor for the development of both community-acquired and nosocomial pneumonia. Presently, the mechanisms by which chronic alcohol abuse alters human pulmonary immunity and increases the likelihood of developing pneumonia are essentially unknown. We hypothesize that increased oxidative stress via glutathione (GSH) depletion leads to abnormal function and viability of human alveolar macrophages (AM), and subsequently impairs alveolar clearance of infectious particles leading to pulmonary infections. In this proposal, the impact of alcohol abuse on the development of pneumonia will be explored by examining the function and viability of AM obtained from two patient cohorts: individuals with a prior history of chronic alcohol abuse and critically ill patients with acute lung injury. Additionally, we will determine the efficacy of oral antioxidant replacement therapy on AM function in individuals with a prior history of chronic alcohol abuse. The goal of this research endeavor is effective medical therapy to decrease the risk of community-acquired and nosocomial pneumonia in the millions of individuals who chronically abuse alcohol. Dr. Ellen Burnham is presently a fellow in Pulmonary and Critical Care Medicine at Emory University. During the next five years, she will work with several investigators in the Emory Alcohol and Critical Care Clinical Research Program in order to develop necessary clinical and basic research skills. With the support of this proposal, Dr. Burnham will not only receive personal supervision from these established clinical and basic investigators, but will also enroll in the Clinical Research Curriculum Award (CRCA) program at Emory University and the Rollins School of Public Health, and obtain a Masters of Science in Clinical Research to further enhance her ability to perform high-quality research. The ultimate goal of this award is to develop an independent research career in "translational" investigation for Dr. Burnham, examining the systemic effects of alcohol abuse as it relates to pulmonary and critical care medicine. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen
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Project Title: ALDO-KETO REDUCTASES AS PART OF CHEMICAL STRESS RESPONSE Principal Investigator & Institution: Barski, Oleg A.; Pediatrics; Baylor College of Medicine 1 Baylor Plaza Houston, Tx 77030 Timing: Fiscal Year 2001; Project Start 17-AUG-2000; Project End 31-JUL-2003
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Summary: Aldo-keto reductases provide protection against environmental and nutritional toxins and carcinogens by detoxification of reactive aldehydes capable of modifying cellular macromolecules. Chemical stress induces the expression of a number of detoxification enzymes. Thus, aflatoxin reductase is induced by ethoxyquin and other antioxidants. Recently it was shown that ethoxyquin and antiobiotic tunicamycin also induce aldehyde reductase, another member of the aldo-keto reductase family. A crucial element of the human aldehyde reductase gene promoter binds transcription factor CHOP, which is induced in cells exposed to chemical stress. Preliminary results suggest that CHOP mediates the induction of aldehyde reductase expression and that both aflatoxin and aldehyde reductases are part of the cellular chemical stress response system, hence their expression is induced in response to toxic insult. The application proposes to: a) evaluate the ability of physiologically relevant compounds to induce aldehyde reductase expression and to find out whether induction of both reductases goes through the CHOP-dependent pathway. B) test the compounds of the two major groups: toxic substrates and chemoprotectors that are known to induce aflatoxin reductase and other drug metabolizing enzymes (e.g. glutathione-S-transferase). C) test the Selected stimuli for their ability to induce CHOP. D) determine whether CHOP plays a role in inducing aflatoxin and aldehyde reductase by testing the effect of CHOP overexpression and deficiency, and known CHOP-inducing agents on the of the reductases expression. e) clone and sequence aflatoxin reductase promoter and examine it for a CHOP-binding element and response elements described to direct antioxidant induction in other detoxification genes. Understanding the nature and mechanism of regulation of aldehyde and aflatoxin reductase expression will potentially assist in the prevention of harmful and carcinogenic effects of toxic aldehydes as well as provide a basis for identifying populations with increased susceptibility to certain environmental agents. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •
Project Title: ANTIAPOPTOTIC ACTIVITY OF ALZHEIMER ABETA Principal Investigator & Institution: Atwood, Craig Stephen.; Professor; Pathology; Case Western Reserve University 10900 Euclid Ave Cleveland, Oh 44106 Timing: Fiscal Year 2001; Project Start 01-JUN-2001; Project End 31-MAY-2004 Summary: Alzheimer's disease (AD) is a debilitating neurodegenerative disease that is characterized by neuronal cell loss and the deposition of protein aggregates. These neuropathological parameters are correlated with the presence of numerous markers of oxidative stress in the cell bodies of neurons suggesting the involvement of oxidative mechanisms in neuronal cell loss and/or protein deposition. Although the sources of the reactive oxygen species (ROS) leading to this oxidative stress have not been clarified, the brain responds to this chronic oxidative challenge by upregulating antioxidant defense systems (eg. increasing SOD1 and glutathione peroxidase expression). We now have three lines of evidence indicating that the increased generation of Abeta in AD also may be a compensatory response to oxidative stress that prevents neuronal apoptosis. Firstly, we have determined from in vitro studies that Abeta has significant antioxidant (superoxide dismutase) activity, secondly, that nanomolar concentrations of Abeta block apoptosis of neurons following trophic factor withdrawal, and thirdly that the Abeta amyloid burden of the AD-affected brain is significantly negatively correlated with oxidative stress markers. In support of these findings, we find fewer oxidative modifications in amyloid deposits and neurofibrillary tangles compared with the cell bodies of the neurons of AD-affected brains. Together, these compelling data provide a plausible physiological explanation for the increased generation of Abeta in AD and
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following head trauma. We hypothesize that as the disease progresses, the chronic overproduction of hydrogen peroxide by neuronal cells, microglia and Abeta amyloid deposits may overwhelm the antioxidant defense systems of the aging brain with the end result that ROS promote the apoptotic demise. Thus, the novel aspect of our hypothesis is the recognition that Abeta generation may be a form of pleiotrophic antagonism, whereby Abeta may be physiologically purposive under "normal" conditions (i.e. moderately increased concentrations of superoxide and/or high reducing equivalents), but may promote neuronal cell death under abnormal conditions (i.e. high concentrations of superoxide and Abeta that lead to excess hydrogen peroxide/low reducing equivalents). The proposed studies will therefore examine the generation of Abeta as a compensatory mechanism to oxidative stress that is both antioxidant and anti-apoptotic in nature while testing whether overwhelming oxidative challenges promote apoptosis. We also will test whether oxidative stress induces neurons to re-enter the cell cycle as a mechanism leading to cell death. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •
Project Title: ANTIOXIDATIVE ROLE OF GPX1 IN VIVO OF TRANSGENIC MICE Principal Investigator & Institution: Lei, Xingen; Animal Science; Cornell University Ithaca Office of Sponsored Programs Ithaca, Ny 14853 Timing: Fiscal Year 2002; Project Start 01-SEP-1997; Project End 31-AUG-2006 Summary: (provided by applicant): Cellular glutathione peroxidase (GPX1), a major selenium (Se)-containing protein in the body, has been widely considered an antioxidant enzyme. Most striking, we have found that although the enzyme protects against oxidative stress mediated by reactive oxygen species (ROS) in vivo and in vitro, knockout of GPX1 actually renders mouse hepatocytes highly resistant to apoptosis and protein nitration induced by 0.4 mM peroxynitnte (OONO-, PN), a potent reactive nitrogen species (RNS). Because this promoting role of GPX1 in the PN-induced oxidative stress is so fascinating, we propose to determine the underlying biochemical mechanism, signal pathway, and metabolic relevance. Our long-term goal is to elucidate the physiological function of GPX1 gene expression in Se nutrition and human health. We will conduct eight experiments to achieve three specific aims. First, we will use both ROS generators and scavengers as well as glutathione synthesis modulators to determine whether moderate elevation of intracellular ROS and glutathione duplicates the GPX1 knockout effect on the PN-induced oxidative stress in mouse hepatocytes. Second, we will use specific inhibitors to test whether the GPX1 action in these cells is signaled by the cytochrome c/caspase 3, poly(ADP-nbose) polymerase (PARP), and mitogen-activated protein kinase (MAPK) pathways. Last, we will find out if and how GPX1 promotes oxidative stress induced by endogenous PN generated from acetaminophen metabolism in mouse hepatocytes and liver. Key assays will be oxidative injuries including DNA fragmentation or strand breaks and protein nitrotyrosine formation, apoptotic signaling including cytochrome c release and activation of caspase 3, PARP, and MAPK, and cell death or histopathology. Our results will unveil a novel function of GPX1 and Se, and help define their dual role in coping with ROS and RNS. These findings may not only enhance our understanding of the mechanisms of Se in preventing cancer, viral infection and chronic diseases, but also lead to fundamental changes in the current theory and application of antioxidants, and shed new light on pathogeneses of many ROS/RNS-related diseases. Therefore, this research will make significant contribution to guiding the optimal use of Se and GPX1 mimic to improve the US public health. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen
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Project Title: ARSENIC TRIOXIDE TREATMENT OF LYMPHOPROLIFERATIVE DISORD Principal Investigator & Institution: Waxman, Samuel; Wiener Professor/ Medical Director; Medicine; Mount Sinai School of Medicine of Nyu of New York University New York, Ny 10029 Timing: Fiscal Year 2001; Project Start 01-FEB-2001; Project End 31-JAN-2004 Summary: As2O3, given by an intravenous infusion empirically designed in China, has become a new therapeutic agent of choice in the treatment of refractory acute promyelocytic leukemia (APL). It is an unusual agent since it is effective in APL patients that are chemotherapy-resistant and at the apparent therapeutic concentration of 1-2 M induces clinical remission with minimal myelotoxicity. Similar to all trans retinoic acid, As203 may be uniquely effective in treating APL since it can induce both differentiation and apoptosis in APL cells in vitro and in vivo. Whether As203 can be extended as a cancer treatment remains to be determined. We elected to extend the use of As203 to lymphoproliferative disorders (LPD). Anecdotal, unpublished reports from China and more recent case reports in the United States suggest that As203 may be an effective treatment of LPD. Consistent with this is our observation that As203 (1-2 M) treatment of cell lines and primary cultures of LPD (B-cell lymphoma, CLL, ALL, multiple myeloma but not T-cell lymphoma) causes significant growth inhibition and, in some cells, measurable apoptosis similar to NB4 cells (t(15:17) APL cell line). As303 is also appealing since it effectively inhibits growth and induces apoptosis in malignant cells with mutant p53, in lymphoma cells with t(14:18) that overexpress Bcl-2 and does not demonstrate cross resistance to taxol and doxorubicin in P388 lymphoma cells expressing MDR-1. As203 probably has multiple effects that contribute to the induction of cell death dependent on dose, cell type or cellular environment. In vitro, As203 in some cells increases H202 accumulation which acts on the mitochrondria to induce caspase dependent apoptosis. However, these observations made in vitro should be interpreted with caution since cellular levels of glutathione and H202 may be artifactually altered in tissue culture media and are likely to differ from that of cells in vivo. Little is known about the consequence of in vivo exposure of 1-2 M As203 and its effect on human malignant cells. We will compare and contrast in vitro and in vivo effects of As203 treatment of LPD cell lines and primary cultures of LPD cells obtained from animals and patients. These materials will be used: 1) to evaluate the importance of the intracellular redox profile and accumulation of H202 and arsenic to As203-induced growth inhibition and apoptosis; 2) to characterize the cellular responses to As203 at mRNA level using cDNA microarray in LPD cells obtained from patients treated with As203; 3) to design combination therapies in vitro and in vivo to improve the sensitivity of LPD cells to As203; 4) we have designed a phase II pilot study to evaluate 0.25 mg/kg/day As203 (2-1/2 higher concentration than used in APL) in the treatment of patients with relapsed and refractory indolent LPD. The study is designed to identify potential surrogate markers of As203 activity. Should our laboratory study identify agents or schedules that enhance the response to As203, we will use them to appropriately modify the initial phase II pilot study. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen
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Project Title: ASTROCYTE MITOCHONDRIA AND NEUROTOXICITY Principal Investigator & Institution: Philbert, Martin A.; Associate Professor of Toxicology, Envir; None; University of Michigan at Ann Arbor 3003 South State, Room 1040 Ann Arbor, Mi 481091274 Timing: Fiscal Year 2001; Project Start 01-JUN-1999; Project End 31-MAY-2002
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Summary: (Adapted from the Investigator's Abstract) Heterogeneity in regional and cellular responses to neurotoxic chemicals has long been recognized, however, the cellular basis for selective vulnerability is poorly understood. Certain nuclei in the phylogenetically older regions of the brain are exquisitely sensitive to several chemically unrelated neurotoxicants. Many of these chemicals perturb mitochondrial glutathione (GSH) homeostasis and energy metabolism. It is hypothesized that regional differences in astrocytic mitochondrial (mt) glutathione homeostasis render specific populations of astrocytes in the brainstem vulnerable to chemically induced energy deprivation syndromes. Chemicals that are widely believed to act on energy metabolism, nevertheless, do not affect all mitochondria equally. Neurotoxicants such as 1,3dinitrobenzene (DNB) which produce damage similar to those observed in "Acute Energy Deprivation Syndromes" (AEDS) or idiopathic mitochondrial diseases also affect glutathione status. While considerable emphasis has been placed on altered energy metabolism in these syndromes, regional, cellular and subcellular glutathione homeostasis have been largely ignored. The relationships and interdependencies between glutathione and energy metabolism are complex and require further investigation with respect to selective neurotoxicant vulnerability. The central hypothesis of this proposal will be tested by addressing the following specific questions: 1) What are the differences in regional, cellular and subcellular glutathione status and homeostasis? 2) Does modulation of cellular antioxidant status alter regional mitochondrial susceptibility to neurotoxicant-induced oxidative stress? 3) Do astrocytic mitochondria selectively metabolize DNB and render themselves vulnerable to glutathione depletion via opening of the mitochondrial permeability transition (MPT) pore? In vitro and in vivo models that produce distinct astrocytic lesions will aid in determination of the role of mtGSH in the etiology of AEDS. The proposed studies will provide information on mechanisms of oxidative stress which contribute to the loss of specific brain cell populations following exposure to neurotoxic chemicals. This work will lead to better understanding of selective vulnerability and its role in neurotoxic syndromes. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •
Project Title: CDNA MICROARRAY TO DETECT CELLULAR RESPONSES TO MIXTURES Principal Investigator & Institution: Buckpitt, Alan R.; Professor and Chair; None; University of California Davis Sponsored Programs, 118 Everson Hall Davis, Ca 95616 Timing: Fiscal Year 2001; Project Start 01-JAN-1999; Project End 31-DEC-2002 Summary: Much of the work in toxicology has focused on delineating the effects of a single chemical entity often at high doses and over short time periods. However, humans are more often exposed to multiple chemicals over long time periods and at lower doses than generally used experimentally. Thus, there is a need to understand potential interactions of exposure to multiple chemical entities at both the cellular and whole organism level. The current request proposes to take advantage of recent developments in analysis of gene expression with high density microarrays to explore the use of this technology to identify alterations associated with exposure to multiple chemicals. This work will build on recent findings showing that the cytotoxicity of the metabolically activated, systemic pulmonary injurant, 1- nitronaphthalene, is considerably enhanced by preexposure to ozone. Two approaches will be utilized. Arrays of genes coding for both Phase I and Phase II metabolizing enzymes, enzymes involved in the synthesis and degradation of glutathione, several heat shock proteins and housekeeping genes will be prepared. mRNA isolated from control and treated
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(nitronaphthalene, ozone and nitronaphthalene plus ozone) rat lung will be used as a template for synthesis of cDNA labeled with fluorescent tags (CY-3 (control) and CY-5 (treated)) and these will be hybridized to the arrayed targets to determine whether treatments cause up or down regulation of genes likely to control the metabolic activation or detoxication of nitronaphthalene. Parallel quantitative histopathology studies will be done to confirm the severity of the pulmonary lesion in all treatment groups. In the second approach, clones from a control rat lung library will be arrayed on glass slides and screened against labeled mRNA from control (CY-3) and treated (CY-5) animals. Clones showing up or down regulation will be sequenced for identification. These studies will test the validity of using DNA arrays to rapidly screen changes in gene expression in response to mixtures of lung toxicants. The combination of dose and time course response studies which include detailed examination of tissues by histopathology will define cellular/molecular events that occur in response to chemical exposure and are expected to explore the validity of using DNA arrays to screen potential chemical interactions. By examining library clones, these studies may identify new genes whose regulation is altered by chemical exposure. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •
Project Title: CONFORMATIONAL TRANSFERASE
DYNAMICS
IN
GLUTATHIONE
S-
Principal Investigator & Institution: Atkins, William M.; Medicinal Chemistry; University of Washington Seattle, Wa 98195 Timing: Fiscal Year 2002; Project Start 10-JAN-2002; Project End 31-DEC-2005 Summary: (provided by applicant): The glutathione S-transferases (GSTs) are a family of detoxification enzymes that metabolize environmental xenobiotics and drugs, including anti-cancer agents, by conjugating them to the tripeptide glutathione (GSH). GSTs also modulate oxidative stress by metabolizing lipid hydroperoxides and lipid hydroxy-enals. GSTs are likely to play a role in sensitivity to atherosclerosis, cataracts, and neurodegenerative diseases. As a canonical family of structurally related proteins, the GSTs provide a model for understanding the evolution of substrate diversity, which apparently correlates with the evolution of protein dynamics in some GSTs. The GSTA11 isoform has two unusual features that may uniquely contribute to its catalytic diversity as a detoxification enzyme. One feature is a catalytic Tyr with an unusually low pKa, which, possibly, provides electrostatic forces and increases solvation of the active site. The ionization state of this Tyr does not change during chemical steps of the catalytic cycle, and the function of the unusual ionization properties remains unknown. The second feature is a dynamic C-terminal helix, which undergoes ligand-dependent redistribution between 'open' and 'closed' conformations. Highly related, nearly structurally identical, GSTs possess C-terminal helices that are 'static' and remain either 'open' or 'closed.' This proposal explores the catalytic function of the Tyr ionization properties and of the C-terminal helix and, in particular, the hypothesis that the two features have co-evolved as an evolutionary bridge between primitive GSTs and highly evolved substrate specific isoforms. In order to understand the structure, function, and dynamics of the GST family, the specific aims of this proposal are: 1) to determine the stage of GSTA1-1 catalysis at which the C-terminus closes; 2) to determine the function of the unusual ionization properties of the active site Tyr; 3) to explore the molecular determinants of substrate diversity by directed evolution of GSTA1-1 and directed deevolution of GSTA4-4. The techniques to be used include x-ray crystallography, NMR, and fluorescence of model ternary complexes, to monitor the C-terminal structure and dynamics. In order to determine whether the C-terminus must be closed in the
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transition state for the chemical step, linear free energy relationships will be exploited. The relationship, if any, between C-terminal dynamics and the ionization of the catalytic Tyr will be explored with stopped-flow kinetic approaches and steady state fluorescence with an engineered Trp reporter. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •
Project Title: CORE--CELL BIOLOGY AND IMMUNOTOXICOLOGY Principal Investigator & Institution: Leid, Mark; Oregon State University Corvallis, or 973391086 Timing: Fiscal Year 2001; Project Start 01-NOV-1975; Project End 31-MAR-2006 Summary: The Cell Biology and Immunotoxicology Research Core serves as a biologically oriented complement to the Chemical/Analytical Cores of the OSUEHS Center to provide a focus of relevance to human health for application of the chemical and physical approaches and expertise available within the other Cores. Thus the Core provides a medium for the initiation of research projects in directions that otherwise may not have been pursued. Core leadership has changed from Dr. Barnes (who left OSU in 1997) to Dr. Leid. Drs. Bayne, Kerkvliet and Reed continue to be in this Core and are joined by recent Center investigators: Drs. Greenwood, Hagen, Ishmael and Vella. Dr. Hedstrom (Associate member of Center) also remains associated with this research core. In addition, there are 2 postdoctoral, 17 graduate students and 12 research assistants. The objectives of this Core are to provide an intellectual resource for pursuits into cellular signaling and hormonal/cytokine control of growth, differentiation, early development and mechanisms of cell death. Specific projects by investigators of this Core include: analysis of T cells with regard to TCDD or Ah receptor and peroxisome proliferators; immunomodulation by xenobiotics; oxidative stress, including mitochondrial dysfunction, glutathione and protein thiols, with regard to cell death and immunotoxicity; age-related effects on mitochondrial functions. This Core serves as a biologically oriented complement to the Chemical/Analytical Cores to provide "a focus of relevance to human health for application of chemical and physical approaches". This Core has assisted with 97 publications since 1995 with about 16 being collaborative studies. Eight past collaborative projects are listed [Dr. Kerkvliet (4); Dr. Barnes (2); Dr. Reed (1);and Dr. Leid (1)]. Future plans include additional joint projects with the more recent Center investigators, e.g., projects between Drs. Ishmael and Leid (cloning PAR. alpha transcriptional coactivators); Drs. Kerkvliet and Ishmael (new cell cultures models to assess cell cycle after exposure to nongenotoxic carcinogens); Drs. Reed and Hagen role of glutathione, iron and vitamin E on myocytes; Drs. Kerkvliet, Reed and Hagen (role of glutathione and vitamin E in apoptosis of lymphocytes); Drs. Kerkvliet, Vella, Leid and Hedstrom (TCDD effects on dendritic cells). Drs. Kerkvliet and Vella will provide the immunological expertise for this Core with Drs. Leid and Reed providing biochemical and molecular expertise. This Core provides biological bridging with the other Cores and Center investigators with support for experimental design fostered through workshops and monthly laboratory meetings. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen
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Project Title: CORE--CELL CULTURE CORE Principal Investigator & Institution: Brown, Lou Ann S.; Professor; Emory University 1784 North Decatur Road Atlanta, Ga 30322 Timing: Fiscal Year 2003; Project Start 01-FEB-2003; Project End 31-DEC-2007
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Summary: (provided by applicant): The Acute Respiratory Distress Syndrome (ARDS) is a common form of acute lung injury with no effective therapy and mortality of 50%. Investigators in this Center application demonstrated that chronic alcohol abuse was the first co-morbid variable to be identified that significantly increases the incidence and severity of ARDS. In this Center application, the mechanisms by which chronic ethanol ingestion predisposes to sepsis-induced acute lung injury will be addressed in alveolar endothelial cells, alveolar epithelial cells, pulmonary fibroblasts, and alveolar macrophages isolated from a rat model of chronic ethanol ingestion. When the role of glutathione availability in ethanol-induced toxicity is the study question, the rats will be fed the glutathione precursors N-acetylcysteine or Procysteine (L-2-oxo-4-thiazolidinecarboxylic acid) either during chronic ethanol ingestion. The purpose of the cell culture core will be to isolate and culture these cells after the appropriate dietary regimen and then distribute the cells to the different projects. For Projects 1 and 2 and Pilot Project 2, the cell culture core will provide primary alveolar type II cells. For Project 1, alveolar macrophages will also be provided. For Project 3 and Pilot Project 2, the core will provide pulmonary fibroblasts and alveolar type II cells from control or ethanol-exposed rats. For Projects 4 and 5 and Pilot Project 2, the core will be responsible for the isolation and culture of pulmonary microvascular endothelial cells. Peripheral neutrophils will also be provided for Project 4. This core will provide cells with maximum reproducibility, efficiency and cost effectiveness. These primary cells will be isolated and cultured in strict endotoxin-free conditions by experienced cell culture technicians. The purity of the cells obtained will routinely be verified using immunohistochemical techniques and functional assays. Cultured cells will be distributed to all investigators according to their requests for studies outlined in their proposals. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •
Project Title: CORE--IMAGE ANALYSIS Principal Investigator & Institution: Burghardt, Robert C.; Texas A&M University System College Station, Tx 778433578 Timing: Fiscal Year 2002; Project Start 05-APR-1998; Project End 31-MAR-2007 Summary: The specific aims of the Image Analysis Facility core are to provide: (1) specimen preparation and imaging of fixed material; (2) technical support for preparation and imaging of immunocyto-chemistry; (3) quantitative single and multiparameter steady-state analysis of vital fluorescence endpoints within living and/or stabilized cells and tissues; and, (4) quantitative single and multiparameter kinetic analysis of endpoints of cellular hemostasis mechanisms. The Image Analysis core is centrally located in the Veterinary Medical Administration building. The primary functions of the core are to provide access to microscopy and image analysis services for the evaluation of cellular hemostasis. Particular emphasis is placed on aims 3 and 4. These two aims are achieved using one of five fluorescence instruments: Meridian ACAS Ultima Interactive Laser Cytometer/Scanning Laser Confocal Microscope, Meridian InSIGHT Point Laser Scanning/Confocal Microscope, Scanalytics CELLscan Fluorescence Deconvolution Workstation, Photon Technologies International Fluorescence Ration Spectrometer, and Zeiss PMIII Light Microscope. Using these instruments, the Image Analysis core personnel have developed and/or adapted commercially available fluorescence probes and naturally occurring fluorescent molecules to monitor the following endpoints in cultured cells: (1) generation of reactive oxygen species; (2) analysis of intracellular pH; (3) determination of mitochondrial membrane potential; (4) detection of intracellular Ca2+ content, Ca2+ fluxes, intrinsic and induced Ca2+ oscillations; analysis of other ions such as Mg2+, Na+, K+, Zn2+, and
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Pb2+ Ca2+ interactions; (5) detection and quantitative assessment of gap junction mediated intracellular communication and metabolic cooperation; (6) analysis of plasma membrane integrity and membrane potential; (7) analysis of lipid and protein mobility in membranes (FRAP); (8) analysis of DNA content, unscheduled DNA synthesis, and quantitation of apoptosis; quantitative analysis of glutathione in single cells or in a cell population; (9) analysis of glutathione-S-transferase activity; (10) analysis of mixed function oxidase activity within specific fluorescence substrates; (11) analysis of (MDR-1 gene expression) p-glycoprotein induction/ expression; (12) analysis of cellular uptake, partitioning, extrusion, and/or metabolism of selected toxicants which are inherently fluorescent; (13) analysis of protein expression and cytoplasmic trafficking of selected proteins; (14) vital imaging of organelles for co-localization studies; (15) activation of "caged" probes (e.g., caged second messengers, neurotransmitters); (16) analysis of endocytotic activity; and, (17) analysis of green fluorescent protein (GFP) as a reporter of gene expression and protein localization. The majority of these applications have been developed in collaboration with Center investigators and new applications are under development. Forty seven references which document the development or application of these methods by core personnel or Center investigators. The core also has micromanipulation and microinjection equipment and methods for cloning individual cells selected in vital assays by laser cytometry. Efforts are in progress to expand services such as the use of a square wave pulse generator to facilitate introduction of xenoproteins into cells or electroinsertion into plasma membranes for functional analyses using non-invasive imaging technologies. The application lists 14 users of this core among the Center?s investigators and at least 17 grants of those investigators that will be supported by this core. This facility core provides its services at a nominal cost to users and has acquired one new instrument every other year over the last nine years. The income from the user fees is used to cover the cost of supplies requests to use the core instruments and services must be made in writing. In general requests are handled on a first-come, first-serve basis. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •
Project Title: DESIGN, SYNTHESIS AND STUDY OF NEW SENSITIZERS FOR PDT Principal Investigator & Institution: Detty, Michael R.; Chemistry; State University of New York at Buffalo Suite 211 Ub Commons Amherst, Ny 14228 Timing: Fiscal Year 2001; Project Start 01-SEP-1996; Project End 31-MAR-2005 Summary: (provided by applicant) The ultimate objective of this research is to provide viable clinical agents useful as sensitizers in the photodynamic therapy (PDT) of cancer. One aim of the proposed research is to design, synthesize, and evaluate new sensitizers for PDT that: 1) are selectively retained in tumors, 2) display no long-term skin photosensitivity, 3) have high quantum yields for the cytotoxic event, 4) deplete glutathione levels during PDT, and 5) absorb longer wavelengths of light where light penetration into tissue is optimal. These desirable features can be obtained by replacing oxygen or sulfur in the sensitizer chromophore with the heavy atoms selenium or tellurium. Selenium and tellurium analogues of both the anticarcinoma agent AA1 and the rhodamine dyes will be prepared and evaluated for their spectral, chemical, and photophysical properties, which include n-octanol water partition coefficients, quantum yields for singlet oxygen generation, pH-sensitive hydrolysis rates, reactivity with singlet oxygen, and rates of reaction of oxidized dyes with glutathione. The biological activity of the new drugs with appropriate spectral, chemical, and photophysical properties will be evaluated in vitro against several cancer cell lines to determine: 1) uptake of the dyes, 2) dark and phototoxicities, and 3) mechanisms of phototoxicity.
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Isolated mitochondrial suspensions will also be used to evaluate mechanisms of phototoxicity. Sensitizers that show promise in the in vitro studies or appropriately modified new derivatives will be evaluated in vivo using a rat mammary tumor model for therapeutic efficacy, pharmacokinetic studies of dye distribution and retention in normal and cancer tissues, and effects on cellular glutathione levels. PDT with the selenopyrylium dye KL-Se, which shows no toxicity at 29 mg (62 umol)/ kg and is selectively retained by tumors, will be optimized to improve upon the 300 percent increase in tumor doubling time (relative to untreated controls) already observed in initial PDT studies with KL-Se. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •
Project Title: DETERMINANTS OF BREAST CANCER SURVIVAL Principal Investigator & Institution: Bondy, Melissa L.; Professor; Epidemiology; University of Texas Md Anderson Can Ctr Cancer Center Houston, Tx 77030 Timing: Fiscal Year 2002; Project Start 01-JUN-2002; Project End 31-MAY-2007 Summary: We propose a molecular epidemiologic cohort study of all newly diagnosed Stage IIA and IIB breast cancer patients who registered at The University of Texas M.D. Anderson Cancer Center (MDACC) between January 1, 1985 and December 31, 1999, and were residents of the state of Texas (N=2,875). This cohort is characterized by extensive long-term follow-up, and equal access to "best of care" practices. It offers us the opportunity to test hypotheses regarding the role of host genetic (i.e., such as gene polymorphisms in drug and radiation sensitivity, family history and ethnicity) and exposure factors (i.e., smoking, reproductive events, BMI, HRT, co-morbid conditions) in relation to tumor phenotype, as independent and interactive determinants of risk of recurrence, distant metastasis, contralateral breast cancer, second malignancies, and/or disease-free survival. In this population, we will examine a series of promising candidate host genetic markers and suspected environmental and lifestyle factors for their added value in clinical decision making when compared or combined with standard histopathological prognostic markers (e.g., lymph node status, tumor size, histological grade). In order to address our study hypotheses, we propose the following 4 specific aims: 1) To compile a comprehensive database of epidemiologic risk factors and clinical data (including treatment, pathology, and long-term follow-up) on all breast cancer patients seen exclusively at MDACC for Stage II disease. 2) To evaluate baseline epidemiologic profiles as independent and inter-related determinants of risk of recurrence, distant metastasis, contralateral breast cancer, new primary malignancies, and disease-free survival. These profiles will include comprehensive information on the use of tobacco, reproductive factors including ovarectomy and the use of HRT, body mass index (BMI), family history of cancer, age and ethnicity in relation to standard histopathology markers. 3) We will evaluate the interaction between these epidemiological factors and a) host and b) tumor molecular markers that show a relationship with disease prognosis and patient events. Specifically, in our sample set we will evaluate: the tumor specific expression of HER2-neu, Ki-67, ER, PR and p53, using standardized immunohistochemical analysis, as informative markers of tumor phenotype and patient performance. Inherited variability in genes that modulate host sensitivity to therapeutic agents, including the glutathione sulfotransferase (GSTpi, GSTM1, GSTT1); enzymes important in defending against chemical injury by catalyzing conjugation of reactive electrophilic molecules with glutathione, and an allele variant in the multi-drug resistance gene MDR-1 whose products, P- glycoprotein, is strongly linked with chemotherapeutic resistance. Our fourth aim is to construct statistical models to determine which marker or combination of markers and host factors (genetic
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and lifestyle) are better predictors of patient performance than the commonly used histopathologic methods. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •
Project Title: DETOXIFICATION OF XENOBIOTICS IN OCULAR TISSUE Principal Investigator & Institution: Awasthi, Yogesh C.; Professor; Human Biol Chem and Genetics; University of Texas Medical Br Galveston 301 University Blvd Galveston, Tx 77555 Timing: Fiscal Year 2002; Project Start 01-SEP-1983; Project End 31-MAR-2006 Summary: (provided by applicant): Lipid peroxidation (LPO) caused by oxidative stress is involved in the mechanisms of cataractogenesis and ocular toxicity in general. LPO products, phospholipid hydroperoxides (PL-OOH) and 4-hydroxynonenal (4-HNE) cause cataracts in animal models, and their concentrations are increased in human senile cataracts. Glutathione (GSH) and its associated enzymatic mechanisms provide protection against the toxic manifestations of LPO primarily through free radical scavenging and glutathione peroxidase (GPx) activity. The alpha class glutathione Stransferases (GSTs) constitute the bulk of GST protein in ocular tissues. We hypothesize that the alpha class GST isozymes, hGSTA1-1 and hGSTA2-2 which reduce PL-OOH through their Se-independent GPx activity, and the isozymes, hGST5.8, and hGSTA4-4 which detoxify 4-HNE through its conjugation to GSH, act as the major antioxidant enzymes and protect ocular tissues from the toxic manifestations of LPO. This hypothesis stems from our preliminary studies showing that hGSTA1-1 and hGSTA2-2 can utilize PL-OOH as substrates, while the major Se-dependent enzyme, GPx 1, can not. GSTs contribute more than 60 percent of the total GPx activity toward PL-OOH in liver and cultured human lens epithelial (HLE) cells, and HLE cell transfected with hGSTA1-1 or A2-2 acquire resistance to H202 and naphthalene induced LPO, cytotoxicity, and apoptosis. Likewise, HL-60 cells transfected with mGSTA4-4 acquire resistance to the cytotoxic, and apoptotic effects of 4-HNE, and pro-oxidants which induce LPO. The following Aims are proposed to validate this hypothesis: 1. To quantitate GPx activity of hGSTA1-1, hGSTA2-2 toward PL-OOH in ocular tissues and cultured cells in relation to Se-dependent GPxs. To examine if these isozymes can reduce membrane PL-OOH in situ in ocular tissues and cells in culture. To examine if HLE and RPE cells transfected with hGSTA1-1, hGSTA2-2 are protected from H202 and naphthalene mediated LPO, cytotoxicity and apoptosis. 2. To clone 4-HNE metabolizing isozyme hGST5.8 and evaluate the relative roles of hGST5.8 and hGSTA4-4 (another 4HNE metabolizing human GST we have cloned) in metabolism of 4-HNE in ocular tissues. To transfect HLE and RPE cells with these enzymes and to examine if their overexpression protects against cytotoxicity, and apoptosis caused by 4-HNE and oxidants such as H202 and naphthalene which promote LPO. 3. To examine if mGSTA44 knock out (-/-) mice lacking the ability to metabolize 4-HNE are more susceptible to naphthalene cataract and toxicity of LPO products during iron overload. These studies will help in understanding the role of LPO in cataractogenesis. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen
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Project Title: DNA METHYLATION AND GSTP1 GENE REGULATION IN GLIOMAS Principal Investigator & Institution: Ali-Osman, Francis C.; Professor and Head; Neurosurgery; University of Texas Md Anderson Can Ctr Cancer Center Houston, Tx 77030
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Timing: Fiscal Year 2002; Project Start 01-SEP-2002; Project End 31-AUG-2007 Summary: (provided by applicant): Human malignant gliomas are among the most intractable of human tumors to therapy. There is, therefore, a continued urgent need for a better understanding of the molecular mechanisms underlying the malignant growth, progression and therapeutic failure in these tumors. Among the most common molecular alteration in brain and other human tumors is the over-expression of the glutathione S-transferase P1 (GSTP1) gene. This application is based on several important findings on the GSTP1 gene in human gliomas that have been made in our laboratory. These include the discovery of allelopolymorphism of the GSTP1 gene locus and the demonstration that GSTP1 gene expression in gliomas is highly heterogeneous and is a strong prognostic indicator of patient survival and response to therapy. Our goal in this application is to better understand the molecular mechanisms that regulate differential GST-pi expression among malignant gliomas. We will test the hypothesis that the heterogeneity in GSTP1 expression among gliomas results from differential transcriptional activity of the GSTP1 gene and that differences in methylation of CpGs in the 5'-region of the GSTP1 gene results in altered chromatin structure and altered transcription factor binding to the GSTP1 promoter, which ultimately accounts for the differences in GSTP1 expression between gliomas. Using both primary specimens and cell lines of human malignant gliomas, we will a) Determine be extent to which differential GSTP1 expression among malignant gliomas is regulated at the transcriptional level; b) Determine the relationship between methylation status of CpGs in the 5?-region of the GSTP1 gene and the transcriptional activity and expression of the GSTP1 gene in gliomas, and examine whether different GSTP1 alleles are differentially methylated and expressed, and whether GSTP1 gene methylation status is associated with drug resistance in gliomas; c) Investigate the effects of the methylation of CpGs in the GSTP1 5'-region on transcription factor binding to the GSTP1 promoter region and on GSTP1 promoter function; d) Examine whether methylation of the GSTP1 gene is associated with altered histone acetylation/deacetylation and chromatin structure at the GSTP1 gene locus, and whether these together determine GSTP1 expression in gliomas. The proposed studies represent a well-focused innovative research effort. The results should yield important new information on DNA methylation-related mechanisms involved in the over-expression of the GSTP1 gene in human gliomas and will contribute to efforts in the rational development of more effective agents and treatment strategies for these tumors. The results should also lead to a better understanding of the malignant process, not only in gliomas, but also in many other human cancer characterized be GSTP1 over-expression. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •
Project Title: DNA REPAIR MEDIATED BCNU RESISTANCE IN CNS TUMORS Principal Investigator & Institution: Friedman, Henry S.; Professor; Duke University Durham, Nc 27706 Timing: Fiscal Year 2002; Project Start 30-SEP-2002; Project End 31-AUG-2004 Summary: (provided by applicant): Malignant central nervous system (CNS) tumors are perhaps the most difficult and frustrating neoplasms to treat, in large part due to the sensitive site in which these 'lesions arise and grow. The role of chemotherapy in the treatment of both malignant glioma and medulloblastoma continues to evolve with modest (in glioma) to more appreciable (in medulloblastoma) successes but new challenges to overcome. The chloroethylnitrosourceas (CENUs) were originally chosen for treatment of central nervous system tumors on the basis of favorable physiochemical properties such as lipophilicity as well as activity against L1210 leukemia cells growing
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intracranially in mice. Nevertheless, despite moderate sensitivity of malignant glioma to BCNC or CCNU, the CENUs have only modestly altered survival for patients with malignant brain tumors. CENUs such as BCNU produce highly reactive 2-chloroethyl carbonium ions following hydrolysis which car bifunctionally alkylate and crosslink DNA, RNA and proteins via ethylene bridges. The anti-tumor activity of CENUs appears to be proportional to DNA interstrand crosslink (ICL) formation. Resistance to alkylating agents including CENUs is multifactorial, with a diverse spectrum of mechanisms observed in murine and human neoplasia. These mechanisms include removal of the initial CENUs-induced mono-adduct by 06 alkylguanine-DNA alkyltransferase or quenching of the mono-adduct by glutathione. However, CENUinduced DNA ICL are not susceptible to either AGT removal or glutathione quenching. Therefore, resistance to CENUs in tumor cells in which DNA ICL are formed must be due to alternative mechanisms other that AGT-or glutathione-tumor cell interactions. The hypothesis of this proposal is that: repair of DNA ICL is 5 major mechanism of resistance to chloroethylnitrosourceas in malignant glioma and medulloblastoma. The specific aims of this proposal are: 1) Define molecular events mediating repair of BCNUinduced DNA ICL by human cell extracts; 2) Define the DNA repair pathways operational in removal of BCNU-induced DNA ICL; 3) Define the role of repair of BCNU-induced DNA ICL in mediating resistance; 4) To conduct Phase 1 and 2 trials of BCNU plus inhibitors of DNA ICL repair in patients with malignant glioma. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •
Project Title: DRUG ABUSE AND REGULATORY ENZYMES OF BIOGENIC AMINES Principal Investigator & Institution: Fleckenstein, Annette.; Professor; Pharmacology and Toxicology; University of Utah 200 S University St Salt Lake City, Ut 84112 Timing: Fiscal Year 2001; Project Start 01-NOV-1973; Project End 31-MAR-2005 Summary: Since 1991, there has been a disturbing increase in the abuse of the potent stimulant, methamphetamine (METH) in both adolescents and young adults. We and others have investigated the short- and long-term effects of METH on dopamine (DA) and serotonergic (5HT) systems of young adult rats (typically 60-90 postnatal day; PND). Because of reports that younger animals (20-40 PND), corresponding to the human adolescent developmental stage, are less likely to experience METH-induced long-term changes in DA systems, little METH-related research has been conducted on this population. In preliminary studies, we confirmed that multiple high doses of METH cause deficits of 50-70 percent in striatal DA parameters after 7 d in 90 PND, but not 40 PND, male rats. In contrast, METH-induced short-term (1 h after treatment) responses by DA systems were very similar in both the 40 and 90 PND groups. Surprisingly, we did not observe an age-dependent difference in either the short- or long-term responses by the 5HT systems to METH treatment. Because of these age-dependent differential responses, it is important to study and compare the effects of METH on both young (corresponding to human adolescence) and more mature (corresponding to human adults) animals. In order to elucidate the age-dependent effects of METH abuse, this proposal will test the hypothesis that there are age-related differential long- but not short-term responses by DA systems to METH; however, the developmental pattern of response to METH is different for the 5HT system. This hypothesis will be tested by achieving the following Specific Aims: A. Determine the pattern of the age-dependent differential response by DA systems to METH, and compare these age-related effects to those observed in 5HT systems. B. Determine the mechanism responsible for the agedependent DA differential responses to METH. C. Determine the consequences of the
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age-dependent differential response to METH. The studies associated with this specific aim are based on the interesting observation that exposure of adolescent rats (i.e., 40 PND), which as noted above, are refractory to the long-term DA deficits caused by METH, makes these animals also refractory when later challenged as adults (90 PND) with high doses of METH. The mechanism and selectivity of this phenomenon will be studied. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •
Project Title: EARLY BIOMARKERS OF LUNG CANCER BY GENE ARRAY ANALYSIS Principal Investigator & Institution: Boggs, Susan E.; Lovelace Biomedical & Environmental Res Environmental Research Inst Albuquerque, Nm 87185 Timing: Fiscal Year 2002; Project Start 01-APR-2002; Project End 31-MAR-2004 Summary: There is a lack of information on the initial events that occur in normal lung epithelial cells upon exposure to environmental tobacco smoke (ETS), a known carcinogen. Although biochemical markers, such as cell cycle state, glutathione (GSH) levels and cytokine secretion have been described for transformed lung cell lines and tumors., little information exists for primary human lung epithelial cells exposed to ETS. Furthermore, no genetic markers in ETS exposed normal human lung cells have been defined to predict tumorigenic potential. Therefore, this application proposes to characterize the biochemical markers, cell cycle state, GSH and cytokine levels, and to identify potential genetic markers of lung tumor development in normal lung epithelial cells due to ETS exposure. This will be accomplished by carrying out the following specific aims. Specific Aim I will determine the temporal profile of these biochemical markers in both primary human bronchial epithelial cells (HBEC) and small-airway epithelial cells (SAEC) exposed to ETS. Specific Aim II will determine the temporal expression profiles of 8,327 genes in HBEC and SAEC exposed to ETS. These profiles will be correlated with respect to cell type (HBEC versus SAEC), temporal changes and the biochemical tumor markers characterized in Aim I. Our hypothesis is that the gene array analysis of these cells will identify a set of genes whose altered expression is predictive of human lung cancer. This gene set coupled with the biochemical tumor markers will have a better predictive value of significant cellular alterations, which impact on the development of lung cancer due to ETS exposure. This approach will extend our knowledge of the effects of ETS on normal primary human lung epithelial, and provide a basis upon which to predict new relationships for genes whose expression is altered by ETS. Expression profiling is expected to provide a new approach for comparisons between normal and cancerous cells, as well as to suggest potential targets for intervention. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen
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Project Title: EFFECTS RELATED BIOMAKERS OF TOXIC EXPOSURES Principal Investigator & Institution: Checkoway, Harvey L.; Professor; Environmental Health; University of Washington Seattle, Wa 98195 Timing: Fiscal Year 2001; Project Start 30-SEP-1987; Project End 31-MAR-2005 Summary: This proposal is for a 5-year competing renewal of the UW Superfund Basic Research Program Project. The theme of this Program Project is that biomarkers measured in accessible tissues are predictive of: a) toxicant exposures; b) early indicators of damage; and/or c) unusual susceptibility to toxic agents that commonly occur at hazardous waste sites. The UW Program Project includes 9 research projects (7
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biomedical, 2 bioremediation), an administrative core, a service core dedicated to molecular biology assays, a training core and an outreach core. The research projects can be divided into four subgroups: 1) laboratory-based development of sensitive biomarkers of adverse effects and disease susceptibility; 2) applications of biomarkers to human populations. 4) biomarker measurements of environmental chemical toxicity in terrestrial and aquatic species and 4) biomarker applications for hazardous waste remediation. Multi-disciplinary cross-project interactions among toxicologists, epidemiologists, molecular biologists and environmental engineers (e.g. measurement of the same biomarkers in various projects to assess a range of effects) have been carefully devised to maximize scientific yield. This project will continue investigations in glutathione biosynthesis biomarker as indicators of oxidative to assess a range of effects) have been carefully devised to maximized scientific yield. This project will continue investigations on glutathione biosynthesis biomarker as indicators of oxidative stress; characterization of novel biomarkers and applications to epidemiologic investigations are newer directions. This project will continue investigations on glutathione biosynthesis biomarker as indicators of oxidative stress; characterization and novel biomarkers and applications to epidemiologic investigations are newer directions. This project will identify genetic polymorphisms of porphyrin synthesis enzymes, and test these as markers of neurobehavioral toxicity in mercury-exposed humans. This project is a new project that will investigate paraoxonase phenotype and genotype inter-relations, with applications to experimental toxicokinetic studies in rats and to an epidemiologic studies of parkinsonism. This project continues to examine epidemiologically the interactions between environmental toxicants and genetic polymorphisms of enzymes involved in xenobiotic activation and detoxification. This project will apply a physiologically-based toxicokinetic model derived from controlled human exposures to organic solvents to characterize determinants of uptake, metabolism, and excretion. This project continues to examine biomarkers of exposure and effect in wildlife residing near or in hazardous waste sites. This project is a continuing study of DNA oxidative damage in fish from polluted and reference water sites. This project will continue to evaluate the effectiveness of genetically- engineered trees for bioremediation of toxic chemicals (e.g., trichloroethylene). This project will involve laboratory and field genetically-engineered trees for bioremediation of toxic chemicals (e.g., trichloroethylene). This project will involve laboratory and field experiments of in situ engineering methods for bioremediation of chlorinated aliphatic toxicants. The Administrative Core, directed by the Program Director, will oversee all major budgetary and personnel aspects of the program project, will coordinate multidisciplinary interactions among research projects and cores, and will assume responsibility for information dissemination and technology transfer. The Program Director will be advised by the Deputy Director, an Internal Executive Committee comprised of research and core directors, and an External Science Advisory Board that includes distinguished environmental scientists from academia and governmental agencies. The Bioanalytical Core will offer genotyping and/or DNA sequencing services to the research projects. The Training Core will ensure that doctoral students and postdoctoral fellows in Environmental Health and Civil Engineering receive crossdisciplinary classroom and research experience. The Outreach Core, which is a new intuitive for this Program Project, will be dedicated to the development of instructional materials relevant to hazardous waste contaminant issues, with an emphasis on biomarker applications for toxicity assessment and bioremediation. The principal audiences for outreach will be K-12 school teachers, health and engineering professionals, and interested community residents. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen
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Project Title: ENDOGENOUS MODULATION OF COCHLEAR INJURY Principal Investigator & Institution: Rybak, Leonard P.; Professor of Surgery; Surgery; Southern Illinois University Sch of Med Box 19616, 801 Rutledge St Springfield, Il 62794 Timing: Fiscal Year 2001; Project Start 01-JUL-1994; Project End 31-MAR-2004 Summary: The optimal use of cisplatin for the best treatment of solid tumors has been prevented because of dose limiting nephro-and ototoxicity. Higher doses of cisplatin may be used with chemoprotectants such as diethyldithiocarbamate (DDTC), which prevents cisplatin toxicity for the kidney and bone marrow. Our preliminary data suggest that DDTC can also prevent cisplatin ototoxicity in an animal model. The proposed research seeks to address the basic question, "Can the ototoxicity of cisplatin be altered by manipulating the glutathione (GSH) content of the cochlea?" A corollary is that the GSH content of the cochlea is related to enzymes of the antioxidant system [superoxide dismutase (SOD), catalase (CAT), and glutathione peroxidase (GSH-Px)] and the enzymes glutathione reductase (GR) and glutathione-S-transferase (GST) and that these enzymes are affected by cisplatin. The specific aims are: 1) to investigate the hypothesis that cisplatin ototoxicity is related to the diminution of the antioxidant system in the cochlea, and that such changes are specific for this target tissue. Physiological changes measured with auditory brainstem evoked response (ABER) testing and endocochlear potential (EP) measurements will be correlated with a) ultrastructural alterations using scanning electron microscopy (SEM) of the organ of Corti and transmission electron microscopy (TEM) of the stria vascularis; and b) biochemical changes in the antioxidant system of the cochlea in comparison to nontarget tissues, the liver and heart, 2) to test the hypothesis that some or all of the ototoxic injury caused by cisplatin is mediated by ototoxic metabolites such as GSH adducts, 3) to examine the hypothesis that the prevention of cisplatin ototoxicity by DDTC is mediated by preservatives of the antioxidant system in the cochlea, 4) to study the pharmacokinetics of cisplatin in plasma and cochlear tissues in ototoxic rats and in animals receiving cisplatin plus the rescue agent, DDTC. The techniques used for this investigation will involve the expertise of three investigators namely physiological measurements (ABER and EP), morphological studies (SEM and TEM) biochemical and metabolic studies: (HPLC) with ultraviolet and electrochemical detection (GSH and GSSG), antioxidant enzymes and other enzymes of the glutathione pathway using spectrophotometry and pharmacokinetic studies by atomic absorption spectrophotometry of platinum levels. These studies should provide new insights into the mechanisms of cisplatin ototoxicity and mechanisms for protection from this doselimiting side effect arising from use of this life-saving chemotherapeutic agent. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen
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Project Title: FACTORS IN THE PREVENTION OF TOXIC LIVER INJURY Principal Investigator & Institution: Boyer, Thomas D.; Professor of Medicine; Medicine; University of Arizona P O Box 3308 Tucson, Az 857223308 Timing: Fiscal Year 2001; 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
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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 •
Project Title: FGF: A MECHANISM OF ACQUIRED MULTIDRUG RESISTANCE Principal Investigator & Institution: Au, Jessie L.; Distinguished University Professor; Surgery; Ohio State University 1960 Kenny Road Columbus, Oh 43210 Timing: Fiscal Year 2002; Project Start 01-SEP-2002; Project End 31-AUG-2006 Summary: (provided by applicant): Development of acquired multidrug resistance (MDR) is a major challenge in cancer chemotherapy. The possible mechanisms include high levels of mdr 1p-glycoprotein and the glutathione transferase (GST) and glutathione (GSH) repair mechanism. But neither mechanism explains the broadspectrum nature of acquired MDR. Alteration of the apoptosis rheostat toward survival could explain the cross resistance among drugs that induce apoptosis through different action mechanisms. The clinical relevance of these mechanisms is not known as studies using Pgp or GSH inhibitors or antisense to Bcl-2 have not improved the efficacy of chemotherapy or have not been completed. We recently demonstrated that two fibroblast growth factors, i.e., acidic and basic FGF (aFGF and bFGF) that are expressed in solid tumors, induce a broad-spectrum resistance (up to 10-fold) to drugs with diverse structures and action mechanisms. Inhibitors of FGF binding to their receptors, including monoclonal antibodies and/or suramin, completely reverse the resistance induced by exogenous FGF. We further found that nontoxic and subtherapeutic doses of suramin enhance the efficacy of paclitaxel and doxorubicin in mice bearing human xenografts. Preliminary results of a phase I trial also suggest that suramin enhanced the efficacy of paclitaxel and carboplatin non-small cell lung cancer patients. Additional preliminary results indicate that short term (72 hour) and long-term (6 months) drug
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treatments enhanced the levels of intracellular and/or extracellular aFGF and bFGF, under in vitro and in vivo conditions, such that the post-treatment FGF levels were sufficient to induce drug resistance. The enhanced FGF levels were due to increased FGF production and secretion, and release of protein upon cell lysis. Drug treatment-induced resistance in cultured cells and xenografts was reversed by suramin. Finally, cDNA microarray results show that bFGF treatment altered the expression of GST, Bcl-2 family proteins, drug efflux proteins, and topoisomerases. These preliminary results, together with the literature data indicating that bFGF enhances GST and shifts the apoptosis rheostat toward survival, have led us to hypothesize that drug treatment induces increases in FGF levels, which in turn lead to acquired MDR, and that acquired MDR can be overcome by FGF inhibitors. The four Aims are as follows. (1) Establish that drug treatment enhances extracellular FGF levels. (2) Test the hypothesis that the FGF induction results in acquired MDR. (3) Test the hytpothesis that FGF is an upstream event that triggers several known mechanisms of acquired MDR. (4) Test the hypothesis that suramin can reverse acquired MDR under in vitro and in vivo conditions. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •
Project Title: GAMMA SUBUNIT GENES
GCS
REGULATION--REGULATORY/CATALYTIC
Principal Investigator & Institution: Mulcahy, R T.; Professor; Human Oncology; University of Wisconsin Madison 750 University Ave Madison, Wi 53706 Timing: Fiscal Year 2001; Project Start 01-FEB-1999; Project End 31-JAN-2003 Summary: The non-protein thiol, glutathione (gamma-glutamyl-cysteinyl-glycine, GSH) is a predominant cellular antioxidant and as such serves critical functions in the maintenance of cellular redox balance, provides protection against reactive oxygen species and is involved in the detoxication of xenobiotics either through direct reactions with reactive intermediates or via enzymatic conjugation reactions catalyzed by glutathione S-transferases. Exposure of cells to a number of xenobiotic agents results in a significant increase in the total intracellular GSH content, secondary to transcriptional up-regulation of the genes encoding the two protein subunits (catalytic and regulatory) of gamma-glutamylcysteine synthetase (GCS, EC 6.3.2.2), the rate-limiting enzyme in its de novo synthesis. It is hypothesized that transcriptional up-regulation of the two GCS subunit genes involves similar cis-elements, but distinct combinations of trans- factors, contributing to differential regulation in response to specific inducting agents. Transcription is hypothesized to involve dimeric transcription factors composed of small Maf proteins and various other bZIP family members, including Nrf1, Nrf2, Fos and Jun. Furthermore, transcriptional activation is hypothesized to be mediated by specific MAPK signaling pathways in response to alterations in the cellular redox balance in favor of a more pro-oxidant state. In evaluating these hypotheses, we propose the following Specific Aims: 1. Finalize analysis of cis- elements within the heavy and light subunit promoters to identify those involved in transcriptional activation of the genes in response to beta-NF; tBOOH; menadione, H202 and PDTC. 2. Identify the transactivating factors and their component proteins which are ultimately involved in binding to the specific cis- elements identified in Aim 1. 3. Determine the role that oxidative stress plays in GCS subunit gene induction. 4. Define the signaling pathway(s) involved in up-regulation of GCS subunit genes. The application proposes a comprehensive investigation of the nature of the signals, the signaling pathways, and the trans- and cis- factors which in composite constitute the mechanism of GCS gene regulation under constitutive conditions and in response to the selective classes of agents included in the investigation.
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Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •
Project Title: GENETIC INFLAMMATION
ANALYSIS
OF
OXIDATIVE
STRESS
AND
Principal Investigator & Institution: Mahaney, Michael C.; Scientist; Southwest Foundation for Biomedical Res San Antonio, Tx 782450549 Timing: Fiscal Year 2002; Project Start 01-JUL-2002; Project End 31-MAY-2007 Summary: (provided by applicant): The objective of Project 4 is to detect, characterize, and localize to chromosomal regions the effects of genes influencing normal quantitative variation in 16 biomarkers which regulate the physiological mechanisms that are related to the processes of oxidation and inflammation or mediate their consequent damage to the human vasculature. Sixteen measures of oxidative stress and inflammation will be assayed and quantified in samples obtained from 950 members of the San Antonio Family Heart Study (SAFHS) extended pedigrees during the first four and a half years of the proposed grant period (SAFHS3). Measures of oxidative stress include: plasma oxidized LDL, F2-isoprostane concentrations, advanced glycation end product, total antioxidant status, plasma concentrations of extra-cellular superoxide dismutase and glutathione peroxidase, and erythrocyte glutathione concentrations, and glutathione concentrations, and gluthathione reductase activities. Inflammation-related phenotypes include white blood cell number, C-reactive protein, tumor necrosis factor-a, interleukin-6, thromboxane A2, and three leukocyte-related adhesion molecules: vascular cellular adhesion molecule-1, intercellular adhesion molecule-1, and P-section. Initial statistical genetic analyses will include more intensive study of previously collected data on a limited number of phenotypes in subsets of the earlier SAFHS1 and SAFHS2 data sets. The purpose of these analyses will be to further explore previously detected genotype-by-sex and genotype-by-smoking effects on total antioxidant status and to determine if these effects extend to other oxidative stress and inflammation phenotypes. Further, using the data obtained for the proposed SAFHS3 sample, pleiotropic (i.e., shared) genetic effects will be sought on variation in multiple oxidative stress and inflammation phenotypes as well as between these phenotypes and other indicators of cardiovascular risk under study in Project 1. Additionally, multipoint whole genome screens will be conducted to localize quantitative trait loci influencing normal quantitative variation in individual and multiple correlated oxidative stress and inflammation phenotypes. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •
Project Title: GENETIC DETERMINANTS OF LUNG CANCER SURVIVAL Principal Investigator & Institution: Yang, Ping P.; Senior Associate Consultant; Mayo Clinic Rochester 200 1St St Sw Rochester, Mn 55905 Timing: Fiscal Year 2001; Project Start 27-SEP-2001; Project End 31-AUG-2006 Summary: (provided by applicant): Prognosis following a diagnosis of primary lung cancer is very poor: The one-year survival rate is only 20-50 percent for advanced disease; the five-year survival rate ranges from 10-60 percent for early stage to under 3 percent for late stage disease. It is vital that survival be improved, because lung cancer will continue to be a significant medical and public health burden for many decades even if all cigarette smokers were to stop. Individualized prognostic predictors are needed. Recent basic science studies suggest that genetic variations in human glutathione (GSH) synthesis and GSH-dependent enzymes (GSH system) are promising candidates for predicting platinum-based treatment outcomes and survival, but their
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interaction with patient characteristics and disease features has not been examined. Platinum compounds (cis- or carboplatin) are used in at least two-thirds of late stage lung cancer patients. We propose to answer an important question: whether patients' genotypes in the GSH system significantly influence lung cancer survival over and above disease stage and treatment modalities. Our primary goal is to test whether genotypes for four important enzymes in the GSH system (gamma-GCS, GSTP1, GSTM1, and GSTT1) predict short-term survival, which is defined as death due to lung cancer occurring within three years of lung cancer diagnosis, among patients treated with platinum compounds. Our secondary goal is to examine multiple risk factors including, in addition to the genotypes stated above, cigarette smoking status, clinical features of lung cancer (disease stage, tumor histology) and treatment modality as modifiers for short-term survival. We will enroll 800 primary lung cancer patients (with stage III and IV disease and treated with platinum compound) and follow these patients for up to three years after their diagnosis at the Mayo Clinic. Histologic subtypes under study include adenocarcinoma, squamous cell, small cell and large cell carcinomas. At least 500 deaths due to lung cancer are anticipated within three years of diagnosis. Our analytic approach is hypothesis-driven, logically progresses from descriptive statistics to survival analysis, and to multiple regression models. From this pharmacogeneticepidemiology study, we will confirm or refute whether genotypes indicative of deficient or absent enzyme activities in the OSH system predict better short-term survival and whether such a survival benefit is only manifested among platinum-treated patients. Our results may suggest a new direction to enhance lung cancer chemotherapy by suppressing or depleting the relevant enzymes. Our results may also assist clinicians in planning patient-specific therapy and more accurately predicting prognosis. Through this project, we will establish a valuable data resource and an infrastructure to study promising biological markers for short- and long-term prognosis of lung cancer patients. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •
Project Title: GENETIC EPIDEMIOLOGY OF GLUTATHIONE AND CF LUNG DISEASE Principal Investigator & Institution: Mckone, Edward; Medicine; University of Washington Seattle, Wa 98195 Timing: Fiscal Year 2002; Project Start 30-SEP-2002; Project End 31-AUG-2007 Summary: (provided by applicant): This proposal is a five-year training plan designed to prepare the Principal Investigator for a career as an independent patient-oriented researcher with an interest in the genetic epidemiology of lung disease. Through the completion of these projects as well as the pursuit of course work in clinical and genetic epidemiology, the candidate will develop the necessary skills to design and implement family-based genetic association studies, including gene-gene and gene-environment interaction. The proposal is a collaboration between the Division of Pulmonary and Critical Care Medicine and the Departments of Public Health Genetics and Environmental Health and includes experts in cystic fibrosis, genetic epidemiology, environmental health and toxicology. The primary scientific goal of this research is to analyze the genetic determinants of lung disease variability in patients with cystic fibrosis (CF). Aim 1 will be a retrospective cohort study, using the National CF database, to quantify the effect of CF genotype on CF clinical manifestations, including lung function and mortality. Aim 2 will be a prospective study to examine for linkage and association between severe CF lung disease and a candidate gene that influences glutathione synthesis. DNA will be collected from CF patients and their biological parents. Transmission disequilibrium testing (TDT) will be performed on the trios
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looking for unequal segregation of glutayl-cysteine-ligase catalytic subunit (GLCLC) polymorphisms from parents to CF patients with severe lung disease. Aim 3 will examine for an association between severe CF lung disease and polymorphisms of glutathione-S-transferase M1 and TNF-alpha also using a TDT. As these polymorphisms may influence glutathione synthesis and function, gene-gene interaction with GLCLC polymorphisms will be examined using a case-only study design and logistic regression. Finally, in aim 4, through the use of validated questionnaires and methods of residence location, environmental exposure to tobacco smoke and air pollutants will be measured to test for gene-environment interaction. These projects have strong clinical and public health implications both in terms of predicting high-susceptibility patients that may develop severe lung disease as well as increasing our understanding of the mechanisms of CF lung function decline. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •
Project Title: GENOTOXICITY OF CHROMIUM COMPOUNDS Principal Investigator & Institution: Zhitkovich, Anatoly; Assistant Professor; Pathology and Lab Medicine; Brown University Providence, Ri 02912 Timing: Fiscal Year 2001; Project Start 01-AUG-1997; Project End 31-JUL-2003 Summary: Exposure to hexavalent chromium compounds has been established to present a significant cancer risk to human respiratory system. Induction of DNA lesions and subsequently, mutations is generally considered to be responsible for the initiation of Cr(VI)-dependent carcinogenic process. Cr(VI) compounds have been shown to be mutagenic to bacterial and mammalian cells, however, the nature of underlying DNA modifications have not yet been characterized. Reductive conversion of Cr(VI) to Cr(III) accompanied by the formation of intermediate Cr(V/VI) forms and radical byproducts is required for the induction of genotoxic effects. Recent data showed that a major form of DNA adducts formed in Cr(VI)-exposed cells is represented by crosslinks composed of intracellular amino acids or glutathione bridged to DNA by Cr(III). Cysteine, histidine and glutamic acid were predominant amino acids found crosslinked to DNA. Subsequent in vitro studies demonstrated that these ternary adducts are formed by binding of Cr(III)-amino acid complexes to DNA. In preliminary experiments some amino acid-Cr(III) adducts exhibited mutagenic activity. On the basis of these data Dr. Zhitkovich hypothesized that a significant portion of Cr(VI) genotoxicity results from reactions of its final reductive metabolite, Cr(III). In order to obtain evidence supporting this hypothesis, a number of experiments aimed at studying formation of Cr(III) adducts and their mutagenic potential will be carried out. Mutagenicity of the in vitro formed Cr(III)- and amino acids/glutathione-Cr(III)-DNA adducts will be investigated in human cells using a shuttle vector approach. Involvement of Cr(III) in the DNA adduction in vivo will be studied in mammalian cells following their exposure to Cr(VI) or particulate Cr(III) compounds. In addition, the role of nucleotide excision repair in the removal of different Cr(III) adducts will also be analyzed. The results of the proposed work will help understand molecular mechanisms of Cr(VI) carcinogenicity by testing a Cr(III)-dependent pathway of DNA damage and mutagenicity of major adducts. Clarification of the genotoxic activity of intracellular Cr(III) may also have important public health implications considering the fact that human exposure frequently occurs to mixtures of Cr(VI) and Cr(III) forms while current risk assessment is based predominantly on the Cr(VI) levels. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen
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Project Title: GLUTATHIONE AND MITOCHONDRIA IN TOXIC RENAL INJURY Principal Investigator & Institution: Lash, Lawrence H.; Professor; Pharmacology; Wayne State University 656 W. Kirby Detroit, Mi 48202 Timing: Fiscal Year 2001; Project Start 01-APR-1988; Project End 31-MAR-2004 Summary: (Adapted from the investigator's abstract): The previous work focused on biochemical properties of glutathione (GSH) transport in isolated renal cells and subcellular organelles. The proposed research will extend those findings by investigating the molecular properties of GSH carrier proteins in kidney mitochondria. The investigators demonstrated previously that two of the known, organic anion carriers of the mitochondrial inner membrane, the dicarboxylate carrier (DCC) and the oxoglutarate carrier (OGC), account for most of the uptake of GSH from the cytoplasm into mitochondria. Specific Aim 1 will involve cloning, expression, purification, and functional characterization of the role of the DCC and OGC proteins in GSH transport. The DCC and OGC genes will be cloned from total rat kidney RNA by RT-PCR, will be expressed in bacteria, purified, and reconstituted into proteoliposomes. The kinetics and inhibitor and substrate specificity of the two carriers will be studies in detail. Specific Aim 2 will test the hypothesis that cellular and mitochondrial function differ in cells transfected with wild-type or mutant GSH carriers. DCC and OGC cDNA clones will be manipulated by site-directed mutagenesis using PCR. Wild-type and mutant genes for these carriers will be expressed in bacteria, purified, and reconstituted into proteoliposomes to assess their activity. Clones of wild-types and mutant carriers will be transfected into stable renal cell line, NRK-52E cells, and the effect of different activity levels of GSH transport on mitochondrial function will be assessed. Mitochondrial play a key role in cellular energetics and in the processes of cellular necrosis and apoptosis. Specific Aim 3 will test the hypothesis that cells transfected with wild-type or mutant mitochondrial GSH carriers have different susceptibilities to oxidant injury, apoptosis and necrosis. Oxidant injury in transfected NRK-52E cells will be induced by tert-butyl hydroperoxide. Cellular and mitochondrial function will be assessed by measurements of respiration, active transport, lipid peroxidation, and GSH status and subcellular distribution. Apoptosis will be quantitated by subdiploid DNA analysis with flow cytometry, measurement of cytochrome c release from mitochondria, activation of caspase-3, and the TUNEL assay for DNA fragmentation. Necrosis will be quantitated by measurements of lactate dehydrogenase release from cells. For each parameter, time and concentration dependent effects will be correlated with GSH transport activity to assess the role of the GSH carriers in the mitochondrial response to toxicants. Achievement of these aims will expand our knowledge of the function of these carriers. This information may have therapeutic applications for prevention of renal cellular injury or for understanding mitochondrial diseases or age-related decreases that occur in mitochondrial function. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen
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Project Title: GLUTATHIONE IN ENVIRONMENTAL TOXICITY AND DISEASE Principal Investigator & Institution: Dalton, Timothy P.; Environmental Health; University of Cincinnati 2624 Clifton Ave Cincinnati, Oh 45221 Timing: Fiscal Year 2003; Project Start 01-SEP-2003; Project End 31-MAY-2008 Summary: (provided by applicant): Reduced glutathione (GSH) is one of the cell's major defenses against oxidative stress. Lowered GSH levels have been implicated in susceptibility to numerous complex diseases (including neurodegenerative disorders, cancer, diabetes mellitus, cataracts, and AIDS) plus toxicity to environmental chemicals
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and heavy metal ions such as cadmium. Levels of GSH vary 10-fold between different cell types. The rate-limiting step in GSH biosynthesis is glutamate-cysteine ligase (GCL). GCL activity exists as the GCL catalytic subunit (GCLC) or as the GCL holoenzyme, a heterodimer composed of GCLC and a modifier subunit GCLM. Using gene targeting, we have generated conventional Gclm(-/-) and Cre-inducible Gclc(-/-) knockout mouse lines. GSH levels in Gclm(-/-) mice are only ~10% of that in Gclm(+/+) littermates in all tissues surveyed, yet, surprisingly, they are viable and fertile. Liver-specific Gclc(-/-) mice die by age 4 weeks, but can be rescued by N-acetylcysteine in the drinking water. With these mice, we are in a unique position to address the hypothesis that Gclm(-/-) mice will be susceptible to both environmental and endogenous toxicants because although the amount of GCLC controls the potential maximum level of cellular GSH, the GCLC/GCLM ratio determines the actual level. Thus, we will: [a] Evaluate endogenous, genotoxicity and oxidative stress in untreated Gclm(+/+) and Gclm(-/-) mice; [b] Assess cadmium-induced liver and kidney toxicity in Gclm(+/+) and Gclm(-/) mice; and [c] Dissect the role of GCLC and GCLM in controlling GSH levels through inducible expression of GCLC and GCLM in double-knockout Gclc/Gclm(-/-) immortalized hepatocytes. By way of these studies, we will define further the role of GCLM and GSH during both heavy metal-induced as well as endogenously-induced oxidative stress, while evaluating the Gclm(-/-) mouse as a model for a compromised oxidative stress response. Further, we will delineate the roles of GCLC and GCLM in controlling GSH levels. These studies will provide valuable insight into understanding the etiology, preventive medicine, and the possible development of therapeutic intervention in the above-mentioned diseases and toxicities. For example, studies suggest that human genetic differences exist in toxicity to cadmium and other environmental toxicants that cause oxidative stress; moreover, the GCLC and GCLM genes are highly polymorphic. Our proposed research should therefore help focus future genotype-phenotype association studies between the appropriate DNA variant sites in the GCLC and GCLM genes and disease. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •
Project Title: GLUTATHIONE REDOX CONTROL OF INTESTINAL CELL RESPONSES Principal Investigator & Institution: Aw, Tak Yee.; Professor; Physiology; Louisiana State Univ Hsc Shreveport P. O. Box 33932 Shreveport, La 71103 Timing: Fiscal Year 2001; Project Start 01-MAY-2001; Project End 31-JAN-2006 Summary: (Scanned from the applicant's description): In the current funding period, we have demonstrated that persistent exposure of the intestine to lipid hydroperoxides (LOOH) induces an imbalance in tissue glutathione (GSH) and glutathione disulfide (GSSG) redox status, impairs peroxide detoxication, and disrupts enterocyte turnover, independently of cell injury. GSH supplementation restores cellular redox balance and maintains normal turnover kinetics. These findings suggest that oxidative stress and the accompanying redox imbalance are important mediators of specific cellular and molecular responses in intestinal cell growth and death. We currently propose to define the role of cellular redox in intestinal apoptosis and proliferation and the mechanisms by which redox mediates these responses. Our central hypothesis is that LOOH-induced redox imbalance mediates transition of intestinal cells from a quiescent state to that of a prohferative or apoptotic state by (differential activation of cell signaling pathways. We further hypothesize that upregulation of mitochondrial MnSOD abrogates mitochondria ROS generation, restores matrix redox balance and attenuates cell apoptosis. The aims address 4 specific hypotheses. Aim 1. To test the hypothesis that LOOH-induced redox
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imbalance differentially mediates intestinal cell proliferation or apoptosis depending on the severity and duration of the redox shift. Aim 2. To test the hypothesis that redoxmediated transition of intestinal cells to the proliferative or apoptotic states is associated with activation of proliferative or apoptotic signaling. Aim 3. To test the hypothesis that redox-induced apoptotic or proliferative signaling is mediated through differential activation of nitrogen activated protein kinases (MAPKs), Akt, or NFkB. Aim 4. To test the hypothesis that upregulation of mitochondrial MnSOD abrogates mitochondrial ROS generation, restores matrix redox balance and attenuates cell apoptosis. The studies will provide (a) important new information on the impact of oxidant challenge and loss of redox balance on regulation of intestinal apoptotic and proliferative responses, and (b) new insights into the potential use of antioxidant enzyme overexpression in the maintenance of metabolic integrity and turnover homeostasis of the intestinal epithelium. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •
Project Title: GLUTATHIONE REDOX POTENTIAL REGULATION OF COLON CANCER CHEMOPREVEN
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Principal Investigator & Institution: Kirlin, Ward G.; Morehouse School of Medicine Atlanta, Ga 30310 Timing: Fiscal Year 2002; Project Start 30-SEP-1987; Project End 31-JUL-2006 Summary: (provided by applicant): Colorectal cancer (CRC) is affected more by dietary factors than any other form of cancer. A better understanding of the mechanisms by which diet is involved in its progression may lead to strategies for its prevention. The importance of these strategies is underscored by its being the third most common neoplasia in the United States. About 6% of individuals in the U.S. will develop invasive CRC during their lifetime. Although there is little difference in incidence between subpopulations in the U.S., world-wide the CRC incidence varies some ten-fold. This wide variation adds to the concept that this cancer may be largely avoidable if causative and preventative factors are discovered. There is strong epidemiological evidence for the benefits of fruit, vegetables and fiber in CRC prevention, with much supportive data from animal studies. There is also experimental evidence indicating that various chemicals either naturally occurring or released upon processing and cooking are involved in the carcinogenesis process. However, many of the chemical compounds thought to be candidates for chemoprevention or cancer initiation and promotion have multiple effects. This is further complicated by the variability in individual genetic susceptibility and response to these dietary compounds. This project utilizes the HT29 human colon cancer cell line to investigate the role of individual dietary factors in stimulating enhanced expression of detoxification enzymes and activating enzymes involved in biotransformation of the model carcinogen benzo[a]pyrene. These studies will be in the context of the effects of dietary chemical compounds on the intracellular glutathione (GSH) redox potential and its role in the signaling process in the regulation of these biotransformation pathways. The relationship between intracellular concentrations of reduced and oxidized GSH, the expression of activator protein-1 and phosphorylation involvement in regulation of these enzymes will be investigated. This study's overall hypothesis is that the carcinogen metabolizing enzymes are influenced by measurable changes in cellular redox status affected by dietary chemical compounds. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen
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Project Title: GLUTATHIONE S TRANSFERASES IN DRUG AND STRESS RESPONSE Principal Investigator & Institution: Tew, Kenneth D.; Senior Member and Chairman; Fox Chase Cancer Center Philadelphia, Pa 19111 Timing: Fiscal Year 2001; Project Start 01-APR-2000; Project End 31-MAR-2005 Summary: This application builds on previous work carried out under the auspices of the OIG awarded to the Principal Investigator. Significant Progress has been instrumental in defining a role for glutathione (GSH) and associated enzymes in detoxification and drug resistance. Our most recent work has provided a framework for assigning novel ways of viewing how glutathione S-transferase pi (GST pi) influences cell response to external stimuli. The present application seeks to extend our efforts in four complementary areas. (i) Determine how acute and chronic drug exposure influences expression of protective stress response genes, with emphasis on drugs which directly influence GSH and related pathways. (ii) Determine how GSH, as a major contributor to thiol: disulfide homeostasis impacts on S-thiolation and glutathionylation of targeted proteins. Altered function of certain enzymes with active cysteine residues will be considered. (iii) Our recent data identify GSTpi as a ligand binding protein and suppressor of C-jun NH2-terminal kinase (JNK). This property may explain the high levels of GSTpi in many solid tumors and drug resistant cell lines, where no obvious catalytic role for GSTpi exists. Experiments are designed to consider a role for GSTPI in cell proliferation and how GSH/GST may impact upon stress kinase biology. Mouse embryo fibroblast cell lines from wild type (GST+/+) and GSTpi knock out (GST-/-) will be used as model cell systems for these studies. The cause/effect relationships between GSTpi inhibitor and an aminothiol drug cause myeloproliferation, part of this study will focus on drug effects on thiol metabolism in bone marrow cells from wild type and GST/- mice. (iv) Pharmacological characterization of two novel therapeutics which target GST pi will be carried out. In addition to the GSTpi was designed to have an enhanced therapeutic index in tumors with high GSTpi levels. Overall, the main emphasis of the present application will be to generate data which link GSH and GST pathways with cellular determinants of stress response and proliferation, and to provide a rationale, preclinical approach to the development of GSTpi targeting drugs. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen
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Project Title: GLUTATHIONE S TRANSFERASES--SUBSTRATE AND SUBUNIT SITES Principal Investigator & Institution: Colman, Roberta F.; Professor; Chemistry and Biochemistry; University of Delaware Newark, De 19716 Timing: Fiscal Year 2001; Project Start 01-APR-1996; Project End 31-JAN-2005 Summary: Glutathione S-transferases (GST) are important in the detoxification of xenobiotics, catalyzing the nucleophilic attack by the thiol group of glutathione on the xenobiotic substrate. Since they catalyze the inactivation of several known carcinogens. Since they catalyze the inactivation of several known carcinogens, these enzymes can provide a defense against carcinogenesis. On the other hand, the elevation of GST levels in solid tumors appears to be a major factor in the development of resistance to treatment with cytotoxic agents. The GSTs are grouped into at least six different gene families based on sequence similarity and substrate specificity; and these isozymes differ in their ability to confer resistance to particular anti-cancer drugs. The amino acid sequences are known for the major dimeric mammalian GSTs and three dimensional structures have been determined for crystals of the pi-class, of the 303 isozyme of the
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mu-class and of the 1-1 isozyme of the alpha-class. However, important questions remain: (1) which amino acids contribute to the specificity of binding of xenobiotic substrates in the various GST isozymes; (2) does a given enzyme have more than one type of xenobiotic substrate site plus other non-substrate (possibly regulatory) sites; (3) which enzymic amino acids are the most important determinants of subunit interaction, as well as what role in the function of the enzymes i played by their dimeric structure. We will examine rat isozyme 1-1 as representative of the alpha-class of GSTs, rat enzyme 3-3 as representative of the mu-class, and pig lung enzyme as an example of the pi-class. These isozymes differ in substrate specificity and comparison of their sequences reveals 79-89% identical plus similar residues within a class, but only about 40% between classes. Our studies of the active sites of these enzymes while in solution will be complementary to and will be compared by computer modeling to structures of the protein crystals using the X-ray coordinates. We plan to use affinity labeling to effect specific modification and identification of amino acids in the xenobiotic substrate and non-substrate sites. We will use site-directed mutagenesis to replace amino acids proposed as participating in subunit interaction, as well as to evaluate the function of amino acids identified by affinity labeling. Mutant enzymes will be expressed and purified, and their monomer-dimer distribution, catalytic and binding characteristics will be examined. This study aims to provide the knowledge base for rational design of inhibitors specific for particular xenobiotic substrate sites for GST for use in novel combination chemotherapy to enhance the efficacy for alkylating cancer drugs. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •
Project Title: GLUTATHIONE S-TRANSFERASE POLYMORPHISMS IN PARK1 PARKIN* Principal Investigator & Institution: Golbe, Lawrence I.; Professor; Neurology; Univ of Med/Dent Nj-R W Johnson Med Sch Robert Wood Johnson Medical Sch Piscataway, Nj 08854 Timing: Fiscal Year 2002; Project Start 15-APR-2002; Project End 31-MAR-2004 Summary: We will examine the hypothesis that mutations in glutathione S- transferase (GST) isozymes influence onset age in Parkinson's disease (PD) caused by the PARK1 mutation. Environmental toxins some of which are degraded by GST-dependent pathways, have been implicated in the cause or onset age of PD. This work takes advantage of the PARK1 "genetic model" of PD to seek insight into genetic and environmental bases for the wide variance in onset age of all PD. In 1997 our group and collaborators reported PARK1, a G209A nucleotide (A53T amino acid) substitution in alpha-synuclein at 4p21 in one Italian and two Greek families. Since then several other Greek families have been reported with PARK1 PD ranges from 22 to 86. Intraneuronal alpha-synuclein aggregation in the form of Lewy bodies occurs as the pathological hallmark of sporadic and mot familial PD, including PARK1 PD. Therefore, explaining the variation in onset age could lead to a means of usefully delaying the onset of all PD. We have preliminary data from 14 affected members of the Italian family (the "Contursi kindred") showing a strong trend a relationship of younger onset age with homozygosity for the A313G allele of glutathione-S-transferase P1 (GST-P1) gene (p=0.51, Mann-Whitney rank sum test; p=.079, 2-sample t-test). We did not examine GST genes other than P1. We now propose to enlarge our N to at least 41 by adding samples from affected members of Greek PARK1 PD families. Our Aims are to 1) Analyze our enlarged set of DNA samples for polymorphic alleles of GSTM1, -M3, -P1, -T1 and -Z1 and determine their effect, alone or in combination, on PD onset age; and 2) Assay GST
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activity in lymphoblasts from affected individuals to determine the functional significance of the mutations we may associated with PD onset age. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •
Project Title: GLUTATHIONE CHEMOPROTECTION
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Principal Investigator & Institution: Townsend, Alan J.; Biochemistry; Wake Forest University Health Sciences Winston-Salem, Nc 27157 Timing: Fiscal Year 2001; Project Start 01-FEB-2000; Project End 31-JAN-2004 Summary: A number of known chemopreventive agents are hypothesized to work in part via induction of glutathione-S-transferase (GST) expression. In order to understand the functions of GST in detoxification of cytotoxic and mutagenic electrophiles, the investigators have utilized transgenic cell lines to show that GST expression can provide efficacious protection against DNA alkylation and, in some cases, cytotoxicity caused by electrophilic carcinogens that are GST substrates, including 4-NQO, B[a]P, BPDE, AFB1, CDNB, and specific drugs. However, the results indicated that the factors governing protection by GST are complex and vary with different agents and endpoints. The studies outlined in this proposal will provide new information on the efficacy and specificity of human GSTP1 or GSTM1 protection against DNA adduct formation or cytotoxicity caused by exposure to PAHs activated in situ by co-expressed rat rCYP1A1 or human hCYP1A1. Heterologous expression of the GST isozymes in V79 cells previously stably transfected with rCYP1A1 or hCYP1A1 will be used as the experimental model system. Importantly, this information will be directly compared with the effects of GST isoenzyme expression on metabolite accumulation and with cellular end-points, such as cytotoxicity, in cells. They hypothesize that the efficacy of the GST system is dependent on multiple factors and not only the enzymatic efficiency with a particular substrate. Several of these factors will be examined in the next funding period, including the relationship between protection by transfected GST isozymes against the above end-points and 1) the level of GST protein expressed, 2) rates and site of activation vs. detoxification, and resultant metabolite profiles and/or levels, 3) cellular factors: glutathione (GSH) supply, and/or efflux of GSH-conjugates, and 4) genetic polymorphisms that affect the active site architecture of hGSTP1-1. These studies will provide a detailed understanding of key parameters affecting the efficacy of GST protection in the transfected cells, and should help to identify the mechanisms of differential protection observed against the various cellular injury end-points examined. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •
Project Title: GLUTATHIONE TRANSFERASE--DEFINING AND ALTERING CATALYSIS Principal Investigator & Institution: Armstrong, Richard N.; Professor; Biochemistry; Vanderbilt University 3319 West End Ave. Nashville, Tn 372036917 Timing: Fiscal Year 2001; Project Start 01-JUL-1982; Project End 31-JUL-2003 Summary: The glutathione transferases catalyze the nucleophilic addition of the sulfur of glutathione (GSH) to a wide variety of endogenous and xenobiotic substrates bearing electrophilic functional groups. They are arguably the single most important enzyme in the metabolism and detoxication of alkylating agents in mammals. In addition, they play diverse catalytic roles in the catabolism of foreign molecules in bacteria. It is the thesis of this proposal hat a thorough understanding of the participation of this group of enzymes in the metabolism of drugs and xenobiotics in both prokaryotes and
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eukaryotes must be based on a detailed knowledge of the relationship between molecular structure and catalytic mechanism. The investigations will focus on poorly understood aspects of the structure and catalytic mechanism of selected mammalian and bacterial enzymes. Four specific aims will be pursued. First, the recently discovered mammalian mitochondrial (class kappa) enzyme, which appears to be more closely related to a bacterial isomerase than to other mammalian GSH transferases, will be investigated by: (i) determination of its three dimensional structure; (ii) the definition of the interaction of the enzyme with GSH by preequilibrium kinetics and mutagenesis; and (iii) isolation and mechanistic analysis of the orthologous 2-hydroxychromene-2carboxylate isomerase in the naphthalene catabolic pathway of Pseudomonas putida. Second, a unique dichloromethane dehalogenase from Methylophylis sp. which appears to catalyze the hydrolytic dechlorination of dihalomethanes without releasing mutagenic S-halomethyl glutathione intermediates during turnover will be investigated. The mechanistic basis for this phenomenon will be established by: (i) steady-state and presteady-state kinetic analysis of the dehalogenation reaction; (ii) a determination of the chemical stability of intermediates in the reaction; (iii) mutagenic analysis of suspected active site residues; and (iv) crystallization and determination of the three-dimensional structure of the enzyme. Third, dimer interface mutants of mammalian class mu enzymes will be studied in an effort to understand the role of the interface in the structural integrity and catalytic activity of individual subunits. These investigations will include: (i) a full mechanistic analysis of mutants at key positions (F56 and D105) identified by X-ray crystallography; (ii) determination of the effects of the mutations on the kinetics of unfolding of the enzyme; and (iii) crystallization and structure determination of the dimer interface mutants. Finally, the enigmatic mechanism of the microsomal enzyme will be explored by: (i) probing the interaction of the enzyme with GSH by preequilibrium kinetic techniques; (ii) mutagenic analysis; and (iii) X-ray crystallography. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •
Project Title: GLUTATHIONE TRANSFERASES AND OXIDATIVE STRESS TOXICOLOGY Principal Investigator & Institution: Zimniak, Piotr; Professor; Medicine; University of Arkansas Med Scis Ltl Rock 4301 W Markham St Little Rock, Ar 72205 Timing: Fiscal Year 2001; Project Start 01-AUG-1996; Project End 31-JUL-2006 Summary: (provided by applicant): Pro-oxidant conditions lead, among other effects, to lipid peroxidation. The ensuing chain reaction yields, for each initiating event, hundreds of lipid hydroperoxide molecules. Some of these give rise to highly electrophilic 4hydroxyalkenals, including the predominant 4-hydroxynonenal (4-HNE). 4-HNE is toxic at high levels but has signaling functions at physiological concentrations. Generally, 4HNE has anti-proliferative differentiating, and pro-apoptotic effects on cells. Both the signaling and toxic outcomes of 4-HNE an thought to be mediated by the compound's ability to cause covalent modifications of proteins, including key regulatory proteins whose function is altered upon 4-HNE adduct formation. Thus, 4-HNE needs to be metabolized to prevent its toxicity (which contributes to the etiology of degenerative diseases such a atherosclerosis or Alzheimer's disease), and to terminate signaling (which may contribute to control of cell division and cell death, and thus be relevant to tumor biology). The major mode of 4-HNE metabolism is glutathione conjugation, catalyzed by specialized glutathione S-transferases. We have previously studied the biochemical and structural properties of mGSTA4-4, a prototypical member of this group of enzymes. In continuation of this project, we propose to shift emphasis to the
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biological properties and physiologic significance of mGSTA4-4. Accordingly, we propose to generate a mGSTA4-4 knockout mouse and stud its phenotype, especially in response to oxidative stress. We further propose to transfect cells with mGSTA4-4 variants which are selectively altered in their partial catalytic properties, and to define the resulting phenotypes. On the subcellular level, we determined that mGSTA4-4 is associated with the plasma membrane, in agreement with the enzyme's function in the metabolism of lipid-derived substrates. We now propose to determine whether the intracellular localization is affected by oxidative stress, and conversely - whether experimental manipulation of localization affects function. Finally, we propose t continue structure-function relationship studies on mGSTA4-4, particularly on a mutant with six-fold increased catalytic efficiency. The proposed work is intended to advance the understanding of the physiological and toxicological consequences of oxidative stress, as mediated by 4-HNE. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •
Project Title: GSTP1 GENE REPRESSION IN PROSTATE CANCER Principal Investigator & Institution: Singal, Rakesh; Medicine; University of MiamiMedical Box 248293 Coral Gables, Fl 33124 Timing: Fiscal Year 2002; Project Start 30-SEP-2002; Project End 31-AUG-2005 Summary: (provided by applicant): Glutathione S-transferases (GSTs) are a group of isoenzymes that catalyze intracellular detoxification reactions by conjugating glutathione with electrophilic compounds including carcinogens and exogenous drugs. Among the isoenzymes, the role of the pi class GSTP (GSTP1) in cancer has been studied extensively. Cytosine methylation in GSTP1 regulatory sequences associated with the loss of GSTP1 expression has been observed in a majority of human prostate carcinomas and prostatic intraepithelial neoplasia (PIN). In normal prostate tissue, in contrast, the CpG island of the GSTP1 gene is not methylated and the gene is expressed. We have recently shown that cytosine methylation can repress the GSTP1 gene expression in LNCaP prostate cancer cells and that this effect is possibly mediated by a Methyl Cytosine-binding Protein complex 1(MeCP1) -like complex. We will elucidate further the mechanism of methylation-mediated GSTP1 gene repression by determining the in vivo binding of methyl CpG binding proteins and histone deacetylases with the GSTP1 gene promoter sequences. Since GSTP1 methylation is an early event in prostate carcinogenesis, it has been proposed that rare prostate cells with hypermethylated GSTP1 promoter sequences may undergo clonal expansion because of carcinogen exposure. GSTP1 is an inhibitor of Jun N-terminal kinase (JNK) activity and pharmacologic or genetic manipulation of GSTP1 influences cell proliferation pathways. At present, it is not known if loss of GSTP1 expression promotes the proliferation and/or tumorigenicity of prostate cancer cells. We will determine if proliferation or tumorigenicity of a human prostate cancer cell line, LNCaP, changes with expression of the GSTP1 gene. We would expect that the results obtained from the studies will be relevant to the development of safe and effective pharmacologic and gene-targeting therapies for patients with human prostate cancer, and will further our understanding of DNA methylation and cancer-associated gene silencing. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen
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Project Title: GSTS: OXIDATIVE STRESS IN EARLY ATHEROSCLEROSIS Principal Investigator & Institution: Boor, Paul J.; Professor; Pathology; University of Texas Medical Br Galveston 301 University Blvd Galveston, Tx 77555
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Timing: Fiscal Year 2002; Project Start 01-APR-2002; Project End 31-MAR-2007 Summary: Atherosclerosis is a major cause of morbidity and mortality. Oxidative stress has been strongly implicated in the pathogenesis of atherosclerosis, but few studies have addressed the mechanisms by which the vascular wall defends against oxidant, or electrophilic, injury. Our recent data show that a specific subtype of glutathione Stransferase (GST), GST A4-4, is selectively induced in vascular smooth muscle cells (VSMCs) of rat aorta in response to electrophilic injury caused by alpha, betaunsaturated aldehydes such as acrolein, 4-hydroxynonenal (4-HNE) and 4hydroxyhexenal (4-HHE), which are toxic end products of lipid peroxidation implicated in the pathogenesis of atherosclerosis. Our recent data in human tissue also supports a role for HGST A4-4 in the pathogenesis of atherosclerosis. Our recent data in human tissue also supports a role for HGST A4-4 in the atherosclerotic plaque. Our hypothesis is that the human vascular GST isozyme, HGST A4-4, functions in the cell's defense against highly reactive alpha, beta- unsaturated aldehydes that are toxic end products of lipid peroxidation, and are implicated in the pathogenesis of atherosclerosis. We expect hGST A4-4 is induced in vascular smooth muscle cells (VSMC) and endothelium during development of the early human atherosclerotic plaque in response to oxidative stress. By manipulating this enzyme in cultured vascular cells from rat, and in genetically altered in vivo mouse models (GST-/-; apoE-/-; a double knock of apoE and GST) we will be able to alter the course of oxidative injury and atherogenesis. Using human blood vessels , our Specific Aim #1 will determine if HGST 4-4 induction and accumulation of suspected aldehyde/aldehyde adducts are early markers of oxidative injury in the early or "fibrous" human atherosclerotic plaque. In Specific Aim #2, we will utilize already- developed rat VSMC, and endothelial cells made resistant to alpha, betaunsaturated aldehydes, to examine the role of GST during oxidative/atherosclerotic stress. In Specific Aim #3 we will use a recently developed genetically altered mouse GST during oxidative/atherosclerotic stress. In Specific Aim #3 we will use a recently developed genetically altered mouse GST knockout of GST and apoE, to manipulate GST A4-4 in order to worsen/hasten the development of atherosclerosis. These studies will focus on early events during oxidative damage and defense mechanisms in the vascular wall, so that therapeutic strategies to prevent initiation and propagation of the atherosclerotic plaque may be devised. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •
Project Title: INHIBITION OF THE ANTICANCER TARGET GLYOXALASE I Principal Investigator & Institution: Creighton, Donald J.; Professor; Chemistry and Biochemistry; University of Maryland Balt Co Campus Baltimore, Md 21250 Timing: Fiscal Year 2001; Project Start 02-APR-1996; Project End 31-JAN-2004 Summary: In this renewal application we propose to continue the development of novel new classes of antitumor agents that function by either reversibly or irreversibly inhibiting the enzymes of the glyoxalase pathway. In the previous funding period, we have demonstrated that enediol analog inhibitors (GSC(O)N(OH)R, where GS = glutathionyl) of the first enzyme in the pathway, glyoxalase I, inhibit the growth of murine and human tumors in vitro and in vivo. Growth inhibition appears to be due to the buildup of cytotoxic methylglyoxal, the substrate for the glyoxalase pathway. We have also discovered an efficient 'sulfoxide prodrug' for rapidly generating the enediol analog inside tumor cells. In addition, we have made major advances in our understanding of the structural biochemistry and mechanisms-of-action of glyoxalase I and the second enzyme in the pathway, glyoxalase II. We will now use this information to develop more potent antitumor agents. The specific aims are: 1.) To synthesize the
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sulfoxide prodrugs CH3(CH)nS(O)C(O)N(OH)C6H4Cl (n = 1,5,8,10), designed to rapidly diffuse into tumor cells and give rise to the enediol analogs via an acylinterchange reaction with intracellular glutathione. 2.) To test for correlations between the structures of the sulfoxides and their ability to deliver enediol analog into L1210 leukemia and B16 melanoma cells, and to inhibit the growth of these tumors, in culture. 3.) To evaluate the pharmacokinetics and antitumor properties of the most promising sulfoxide prodrugs in mice bearing B16 melanotic melanoma. 4.) To determine the molecular basis of active-site directed irreversible inactivation of GlxI by S-(4-bromo-2,3dioxobutyl)glutathione. 5.) To synthesize affinity labels of human GlxI, which target either Glu172 or Cys60 in the active site. Some of the affinity labels are designed to be hydrolyzed by GlxII, an enzyme activity that is high in normal cells but low in tumor cells. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •
Project Title: INTRAOCULAR TRANSPORT AND METABOLISM Principal Investigator & Institution: Reddy, Venkat N.; Senior Research Scientist; Ophthalmology and Visual Sciences; University of Michigan at Ann Arbor 3003 South State, Room 1040 Ann Arbor, Mi 481091274 Timing: Fiscal Year 2001; Project Start 01-MAY-1979; Project End 31-MAY-2005 Summary: (provided by applicant): Cataracts are the leading cause of blindness worldwide, accounting for 42 percent of all blindness. The long-term goal of this application is to provide an understanding of the role of oxidation in the etiology of human age-onset cataracts. Transgenic animal models and gene knockouts for specific antioxidant enzymes serve as powerful tools to assess the role of these enzymes in cataract formation. We have recently found that gene knockout of glutathione peroxidase-l (GPX-l) leads to increased nuclear light scattering (NLS) compared to agematched controls. The increased NLS appears to be related to lens fiber membrane damage as seen by transmission and confocal microscopy. The hypothesis that deficiency of GPX-l leads to membrane protein modification and lipid peroxidation in nuclear fibers will be tested by Scheimpflug slit lamp and dynamic light scattering measurements. Attempts will be made to study changes in lens transparency in other transgenic animal models, which lack the enzyme CuZn superoxide dismutase (CuZnSOD). Additional specific aims are to up and down regulate Mn superoxide dismutase and CuZnSOD in the recently established human lens epithelial cell line (SRA 01/04) by transfection with plasmids containing sense and antisense cDNA for these enzymes. We will then subject the cells to various oxidative challenges including H202, X-ray, UV radiation and hyperbaric oxygen to study their effect on cation transport and cell membranes. The efficiency of transfection will be determined by enzyme assays, Western and Northern blot analyses. The ability of these cell lines to resist the cytotoxic effects of oxidative stress will be assessed from changes in cell proliferation, cell morphology, DNA strand breaks, immunocytochemistry, protein modification and lipid peroxide formation. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen
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Project Title: ISOTHIOCYANATES IN THE CHEMOPREVENTION OF BLADDER CANCER Principal Investigator & Institution: Zhang, Yuesheng; Roswell Park Cancer Institute Corp Buffalo, Ny 14263 Timing: Fiscal Year 2003; Project Start 01-AUG-2003; Project End 31-JUL-2008
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Summary: (provided by applicant): This Project focuses on determining the cancerpreventive activity of isothiocyanates (ITCs) in the bladder. The hypothesis to be tested is that selected ITCs can suppress bladder carcinogenesis by disrupting multiple steps in the carcinogenic process: induction of Phase 2 enzymes, induction of apoptosis, and inhibition of cell proliferation. Molecular markers relevant to these biological events, as well as inhibition of tumorigenesis, will be studied. Bladder cancer is an important health problem; effective chemopreventive agents are needed. ITCs are abundant in vegetables and many are known anticarcinogens in non-bladder animal organs. Ingested ITCs are efficiently absorbed and almost exclusively excreted in urine as Nacetylcysteine conjugates (NAC-ITCs), which also are anticarcinogens and can release ITCs, making the bladder epithelium the most exposed tissue to ITCs/NAC-ITCs. The overwhelming majority of bladder cancers originate from the epithelial cells. Four dietary ITCs that displayed potent anti-carcinogenic activity in non-bladder animal organs and their NAC conjugates will be evaluated. Aim 1 is designed to see whether ITCs or NAC-ITCs effectively induce critical Phase 2 detoxification enzymes, including glutathione transferase, quinone reductase-1, and UDPglucuronosyltransferase, whose deficiencies have been linked to increased bladder carcinogenesis. Aim 2 will determine the protective efficacy of ITCs or NAC-ITCs against carcinogen-induced DNA damage in bladder epithelial cells, using total DNA adducts and unscheduled DNA synthesis (UDS) as markers. Imbalance between apoptosis and proliferation also is a risk factor of bladder cancer. Aim 3 will determine whether ITCs or NAC-ITCs can correct the imbalance between apoptosis and proliferation associated with bladder carcinogenesis: Do ITCs or NAC-ITCs induce apoptosis and/or inhibit cell cycle progression in bladder cancer cells? If so, what is the underlying mechanism(s)? Aim 4 will evaluate in rivo the effect of orally administered ITCs on important biomarkers, including the Phase 2 enzymes described in Aim 1, apoptosis (TUNEL), and proliferation (PCNA) in the bladder epithelium of F344 rats. Aim 5 will determine the efficacy of an orally administered ITC in inhibiting N-butyl-N- (4-hydroxybutyl)-nitrosamine-induced bladder tumorigenesis in F344 rats. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •
Project Title: MAGNETIC RESONANCE IMAGING OF GLUTATHIONE IN TUMORS Principal Investigator & Institution: Gamcsik, Michael P.; None; Duke University Durham, Nc 27706 Timing: Fiscal Year 2002; Project Start 16-AUG-2002; Project End 31-JUL-2004 Summary: (provided by applicant):Glutathione is a tripeptide normally found in high concentration in normal tissue and frequently elevated in tumor tissue. Glutathione and its oxidized disulfide form the primary reduction/oxidation (redox) buffer in cells. The redox balance in the cell controls gene expression, cell differentiation, proliferation and apoptosis and, therefore, it is not surprising that this balance may be elevated in cancer. In normal tissue glutathione protects the cell from toxicants and the cancer cell has adapted this defense mechanism to shield cells from the effects of anticancer therapies. This results in further elevations in glutathione metabolism in therapy-resistant tumors. Therefore, the accurate determination of glutathione in extracts from normal and tumor tissue has proven to be invaluable to predicting therapy response in patients. This proposal outlines the development of magnetic resonance imaging (MRI) methods to non-invasively monitor glutathione metabolism in normal and tumor tissue. Several MRI methods will be evaluated including the use of 1H-editing, 2H NMR and 13Cchemical shift imaging. Using the most sensitive method, in vivo images of glutathione
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content obtained from 9L glioma tumors implanted in the flank of rats will be compared to the concentrations measured biochemically in tissue extracts. All of the imaging modalities will measure static glutathione and require the use of stable isotope incorporation. Isotope incorporation-based methods also allow monitoring of the rate of glutathione metabolism in tissue. These types of dynamic studies may be as important as measuring static glutathione levels to stage tumors and predict therapy response. Due to the unique role played by glutathione in cell proliferation, differentiation and apoptosis, the non-invasive monitoring of glutathione metabolism would offer novel diagnostic and prognostic information on the tumor tissue. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •
Project Title: MECHANISMS OF ENDOTHELIAL DYSFUNCTION IN DIABETICS Principal Investigator & Institution: Beckman, Joshua A.; Brigham and Women's Hospital 75 Francis Street Boston, Ma 02115 Timing: Fiscal Year 2001; Project Start 13-AUG-1999; Project End 31-JUL-2004 Summary: Vascular disease is the principal cause of death and disability among the 12 million patients in the United States with diabetes mellitus. Macrovascular complications, including myocardial infarction, stroke, and amputation are the leading cause of morbidity and mortality among this cohort of patients. Reduced bioavailability of endothelium-derived nitric oxide has been implicated in atherogenesis and may be a fundamental factor in the development of vascular disease in diabetes. Increased degradation of nitric oxide by reactive oxygen radicals and inhibition of nitric oxide synthase via activation of protein kinase C are each potential mechanisms to account for decreased nitric oxide. The sponsor's laboratory has demonstrated impaired endothelium-dependent vasodilation in patients with diabetes mellitus and in healthy, nondiabetic subjects with experimental hyperglycemia. Further experiments showed that vitamin C improved endothelium-dependent vasodilation implicating a culpable role for superoxide. The soluble, glutathione-dependent antioxidant pathway, responsible for detoxification of polar peroxides, is also adversely affected by hyperglycemia and may represent a specific physiologic mechanism causing, in part, the impaired endothelial function demonstrated in diabetes mellitus. This proposal will examine the effect of ebselen, a glutathione peroxidase mimetic on endothelial function in subjects with diabetes mellitus (type I and type II) and healthy, age-matched controls to determine if polar peroxides play an important role in endothelial dysfunction in diabetes. Hyperglycemia causes the up-regulation of protein kinase C isoform beta2 (PKC beta2) which may phosphorylate nitric oxide synthase, reducing its activity. This proposal will also examine the role of LY333531, a PKC beta2 inhibitor, on endotheliumdependent vasodilation in forearm resistance and conduit vessels in subjects with type I and type II diabetes mellitus and age-matched health controls. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen
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Project Title: MECHANISMS OF METHYLMERCURY INDUCED NEURONAL TOXICITY Principal Investigator & Institution: Aschner, Michael; Professor; Physiology and Pharmacology; Wake Forest University Health Sciences Winston-Salem, Nc 27157 Timing: Fiscal Year 2001; Project Start 01-APR-2000; Project End 31-MAR-2004 Summary: (Adapted from the Investigator's Abstract) Methylmercury (MeHg) is a significant environmental contaminant that continues to pose a great risk to human health. Considerable attention in the scientific and health policy fora is focused on the
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question of whether MeHg intake from a diet high in fish is associated with aberrant CNS function. A number of recent studies (Kjellstrom et al., 1986, 1989; McKeon-Eyssen et al., 1983; Grandjean et al., 1997) suggest that fetal exposure at levels attained by mothers eating fish regularly during pregnancy are associated with neurological deficits in their offspring. Astrocytes play a key role in MeHg-induced excitotoxicity. [1] MeHg preferentially accumulates in astrocytes. [2] MeHg potently and specifically inhibits glutamate uptake in astrocytes. [3] Neuronal function is secondary to disturbances in astrocytes. [4] co-application of nontoxic concentrations of mercury and glutamate leads to the typical appearance of neuronal lesions associated with excitotoxic stimulation. [5] MeHg induces swelling in astrocytes. These observations are fully consistent with MeHg-induced dysregulation of excitatory amino acid homeostasis, and indicate that a glutamate-mediated excitotoxic mechanism is involved. The working hypotheses of the proposal outline a number of critical target sites for MeHg-induced neurotoxicity. In Specific Aim 1.0 we will test the hypothesis that activation of the astrocyte-specific enzyme, cytosolic phospholipase A2 (cPLA2) and the ensuing hydrolysis and release of arachidonic acid (AA) are mediators of glutamate release upon exposure to MeHg. We will investigate the lipase(s) involved, and determine the relationship between cPLA2 activation, regulatory volume decrease (RVD), and glutamate release. In specific Aim 2.0, we will test the hypothesis that MeHg-induced increased extracellular glutamate concentrations will competitively inhibit cystine transport into astrocytes, leading to diminished supply of cysteine for neuronal glutathione (GSH) synthesis. In Specific Aim 3.0, we will test the hypothesis that modification of cysteine residues by MeHg is associated with altered glutamate transport, and that it is regulated by the chemical redox-state of reactive cysteine residues in the astrocyte-specific glutamate transporters, GLAST and GLT1. The studies will be carried out in rat primary cultures of neurons and astrocytes, as well as Chinese hamster ovary (CHO-K1) cells (where transporters can be over expressed in cells that lack the endogenous glutamate transporter). Our approach will encompass a broad array of methods, including molecular biology, electrophysiology, radiolabel trans-membrane fluxes, and electrical impedance measurements of cell volume. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •
Project Title: MECHANISMS OF OXIDATIVE INJURY IN VASOGENIC EDEMA Principal Investigator & Institution: Chan, Pak H.; Professor; Neurosurgery; Stanford University Stanford, Ca 94305 Timing: Fiscal Year 2001; Project Start 01-FEB-1988; Project End 31-JAN-2004 Summary: (Adapted from Investigator's abstract): Vasogenic edema is the most common form of brain edema observed in clinical practice. It is characterized by an increased permeability of brain capillary endothelial cells to macromolecules and by an increased extracellular space and brain water. Although the causes of vasogenic edema following brain ischemia and injury appear to be multifactorial, the basic mechanisms are dependent upon alteration sin the structural and functional integrity of brain endothelial cells. we have postulated that oxygen radicals, superoxide radicals in particular, are involved in the perturbation of the structural and functional integrity of the endothelial cells. We have demonstrated that cerebral edema and infarction induced by either cold injury or by focal cerebral ischemia and reperfusion are significantly reduced in transgenic (Tg) mice overexpressing human CuZn-superoxide dismutase (SOD-1) activity. We now propose to continue to investigate the role of oxidative stress in the pathogenesis of vasogenic edema using both in vivo mouse models of focal cerebral ischemia and reperfusion and in vitro cerebral capillary endothelial cell
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cultures. Our specific aims are: 1) to elucidate the role of CuZn-SOD in vasogenic edema and infarction following focal cerebral ischemia and reperfusion in SOD-1 transgenic mice and in sod-1 knockout mutants; 2) to investigate the temporal pattern of bcl-2 and hsp 70 gene expression in neurons and endothelial cells in mice that overexpress SOD-1 transgene, wild-type or in mutant mice with reduced sod-1 expression following focal cerebral ischemia and reperfusion; 3) to elucidate the superoxide-dependent oxidative pathways involving the pathogenesis of vasogenic edema after focal cerebral ischemia using genetically modified mice with altered levels of glutathione peroxidase and nitric oxide synthase activities; 4) to investigate the role of oxidative stress in vasogenic edema and infarction in a newly developed mitochondrial manganese superoxide dismutase (sod-2) knockout mutant mouse; and 5) to study the role of superoxide dismutase on hypoxia-induced injury and degeneration in primary culture of cerebral endothelial cells of Tg and knockout mutants. These studies have therapeutic implications and will further shed light on molecular and cellular mechanisms underlying the pathogenesis of vasogenic edema following ischemia and reperfusion. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •
Project Title: MITOCHONDRIAL DYSFUNCTION IN ALZHEIMER'S DISEASE Principal Investigator & Institution: Beal, M Flint.; Professor; Neurology and Neuroscience; Weill Medical College of Cornell Univ New York, Ny 10021 Timing: Fiscal Year 2001; Project Start 01-SEP-2001; Project End 31-AUG-2005 Summary: There is substantial evidence that the pathogenesis of Alzheimer's Disease (AD) may involve mitochondrial dysfunction and oxidative damage. Mitochondrial dysfunction could occur as either a consequence of primary genetic mutations or due to acquired mitochondrial DNA (mtDNA) mutations, which may be related to oxidative damage. In the present proposal, we will examine whether there is an increased incidence of mtDNA mutations in postmortem brain tissue from AD patients as compared to normal controls. We will utilize direct mtDNA sequencing as well as denaturing gelelectrophoresis to detect low frequency mutations, and we will correlate levels of 8-hydroxy-2- deoxyguanosine (OH8dG), a marker of oxidative damage to DNA. We have developed a sensitive and accurate assay for OH8dG, which is useful in examining concentrations in body fluids. We intend to utilize this assay to measure OH8dG in urine, plasma and CSF of AD patients and controls. We will make cybrids utilizing platelets obtained from well characterized AD patients. *-amyloid deposition may cause oxidative stress and/or oxidative stress may increase -amyloid production. We will examine whether transgenic mice with the APP V717F mutation have increased mtDNA mutations as assessed by direct sequencing. We will correlate this with concentrations of b-amyloid as measured by ELISA, as well as markers of oxidative damage including malondialdehyde, OH8dG and 5-nitro-gamma-tocopherol. We will examine transgenic mouse lines which are deficient in the mitochondrial free radical scavenging enzyme manganese superoxide dismutase. We will also utilize mice, which are deficient in glutathione peroxidase, which detoxifies hydrogen peroxide within mitochondria. We will determine whether these mice develop age-dependent increases in oxidative damage within mtDNA, increased numbers of mtDNA mutations and whether this correlates with increases in extractable levels of b-amyloid. These studies are designed to help to further elucidate the role of mitochondrial dysfunction and oxidative damage in normal aging and AD. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen
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Project Title: MODIFICATION OF MITOCHONDRIAL PROTEIN IN AGING Principal Investigator & Institution: Henderson, George I.; Professor of Medicine & Pharmacology; University of Texas Hlth Sci Ctr San Ant 7703 Floyd Curl Dr San Antonio, Tx 78229 Timing: Fiscal Year 2001; Project Start 01-APR-2001; Project End 31-MAR-2006 Summary: (from the application): There is compelling evidence that oxidative stress contributes to the age-related declines of important physiological functions. Studies have documented age-related impairment of mitochondrial respiration and enhanced production of a toxic product of lipid oxidation, HNE as well as oxidative stress related inhibitory modifications of COX and the adenine nucleotide transporter (ANT) by HNE. COX, a key component of the mitochondrial respiratory chain, declines with aging (as does ANT) and is damaged in diseases associated with the aging process. Additionally, while the underlying cause of age related oxidative stress remains to be defined, leakage of electrons from the bc 1 complex may be a primary source of reactive oxygen species within the mitochondrion. Thus, we hypothesize that age-related oxidative stress damages key components of the mitochondrial respiratory chain by oxidation of cardiolipin and by direct inhibition by HNE. Additionally, these inhibitory modifications can be mitigated by enhancement of mitochondrial antioxidant stores. Specific Aim 1 will establish HNE production and oxidative damage to cardiolipin as factors in the inhibition of COX, ANT, and bcl by aging. Experiments will determine effects of aging on production of HNE, distribution of HNE modifications of COX and bc 1 subunits and damage to the ANT molecule, formation of lipid hydroperoxides within mitochondria (focus on cardiolipin), and changes of antioxidant defenses that may predispose key mitochondrial proteins in the aging brain and liver to damage. Specific Aim 2 will establish HNE adduct formation and cardiolipin oxidation as specific means by which age related oxidative stress inhibits COX. It will address mechanisms by which specific age-related modifications of COX impair its activity. Studies will determine crosslinked and HNE labeled products of COX, identify specific sites of HNE labeling within each subunit, and quantify the role of cardiolipin oxidation in impaired COX activity. One rationale for SA2 is that it will directly link age-related effects on protein function to oxidative stress-mediated modification of the molecule. Specific Aim 3 will determine the roles of glutathione peroxidase4, Mn superoxide dismutase, glutathione, and a-tocopherol in protection of COX, ANT, and bcl from age-related modifications. Mitochondria from brains and livers of wild type and genetically altered mice will be used for all studies. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen
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Project Title: MOLECULAR GENETICS OF HNPCC Principal Investigator & Institution: Frazier, Marsha L.; Associate Professor; Epidemiology; University of Texas Md Anderson Can Ctr Cancer Center Houston, Tx 77030 Timing: Fiscal Year 2001; Project Start 01-JUN-1997; Project End 31-MAY-2006 Summary: The overall goal of this proposal is to build upon and expand our unique clinical and specimen resource of hereditary non-polyposis colorectal cancer (HNPCC) patients to further elucidate genetic and epigenetic factors associated with increased risk for HNPCC. Epidemiologic data will be obtained on 400 subjects carrying germline mutations in either the hMSH2 or hMLH1 gene. It is hypothesized that genes playing minor roles in risk of cancer, modifier genes, are important in predicting risk of colorectal cancer in HNPCC. Polymorphisms in cell cycle genes such as cyclin D1, p53,
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and p21, will be studied to determine if they influence age of onset in HNPCC. Environmental factors, particularly those involving the folate pathway and heterocyclic amines intake will be studied to determine if they are associated with risk of HNPCC. Polymorphisms in metabolic genes such as N- Acetyltransferase 1 (NAT1), NAcetyltransferase 2 (NAT2), Glutathione S-transferase M1 (GSTM1), Glutathione Stransferase T1 (GSTT1), will be studied to determine if they influence age of onset of HNPCC, and then to determine if any of the four genes, in combination with dietary intake data (with emphasis on heterocyclic amines) influence age of onset in HNPCC. A polymorphism of the Methylene tetrahydrofolate reductase (MTHFR) gene at codon 677 will be studied to determine if it influences age of onset of HNPCC, and then to determine in combination with dietary intake data (with emphasis on folate) if it influence age of onset of HNPCC. Models will be developed to predict i) the risk that an individual with MMR mutation will develop specific cancers and ii) the probability that a CRC patient will have a MMR mutation given the age at onset, MSI status (where known), and family history. For the first type of model, we will use the newly developed kin-cohort approach. To predict the probability that an individual is a mutation carrier, we will apply logistic regression and Classification and Regression Trees (CART). This will be the first large systematic study on the roles of modifier genes in HNPCC. The proposed studies will provide important information regarding underlying genetic and epigenetic factors involved in colorectal carcinogenesis in HNPCC and has the potential to provide novel insights into the molecular pathways that might influence this process. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •
Project Title: RESISTANCE
MOLECULAR
MECHANISMS
OF
NITROSATIVE
STRESS
Principal Investigator & Institution: Stamler, Jonathan S.; Professor; Medicine; Duke University Durham, Nc 27706 Timing: Fiscal Year 2001; Project Start 01-AUG-1999; Project End 31-JUL-2003 Summary: (Adapted from the Applicant's Abstract): Nitric oxide (NO) and NO-derived nitrosating agents (nitrosants) are signaling molecules. Protein and low mass thiols are components of signal transduction circuits subject to NO regulation. NO can also be cytotoxic when levels exceed a dangerous threshold. Under such conditions, nitros(yl)ation of cellular constituents imposes a nitrosative stress, which manifests in mutagenesis, cytostasis and cell death. Resistance to the toxic effects of NO-derived molecules is, thus, an indispensable requirement for normal cell function. In E. coli, Snitros(yl)ation of the transcription factor OxyR activates antioxidant genes and, moreover, protects against a nitrosative threat. Part of the resistance is due to accelerated breakdown of S-nitrosothiols (SNOs). Additional protection is conferred by glutathione and the inducible flavohemoglobin HMP that metabolizes NO to nitrate. The proposed study uses this bacterial model system to further probe resistance mechanisms. Aim1. Elucidates the pathway in E. coli that metabolizes SNOs and provides resistance to SNO-induced cytostasis. In this pathway, SNO is cleaved to release NO, and is also reduced to nitrous oxide. The free NO released is oxidized to nitrate by the SNO/NO-inducible HMP. Reaction mechanisms will be identified and the enzymes involved in SNO breakdown will be purified and characterized. Aim 2. Studies the contributions of the antioxidant/antinitrosant glutathione, the transcription factor OxyR, and the 'denitrosolase' HMP in aerobic and anaerobic nitrosative stress resistance. Aim 3. Explores the ability of antinitrosative enzymes to ameliorate nitrosative stress in mammalian systems, specifically, in septic shock and cancer models. Aim 4. Employs
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circular dichroism and X-ray crystallography to reveal the functional redox-related switch that regulates OxyR. The reduced, oxidized, mixed disulfide and nitrosylated forms of purified OxyR are analyzed and their functional behaviors compared. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •
Project Title: 'MOLECULAR UMBRELLAS AS MEMBRANE TRANSPORTERS' Principal Investigator & Institution: Regen, Steven L.; University Distinguished Professor; Chemistry; Lehigh University Bethlehem, Pa 18015 Timing: Fiscal Year 2002; Project Start 01-DEC-1994; Project End 31-JUL-2006 Summary: The overall objectives of this research are to gain a deeper understanding of the mechanism by which molecular umbrellas transport polar molecules across lipid bilayers, to define the scope of molecular umbrella-assisted bilayer transport, and to develop cleavable molecular umbrella conjugates with a view towards the development of prodrugs. The long-term goal of this program is to develop molecular umbrellas as membrane transporters of biologically-active agents for oral delivery, for delivery across the blood-brain barrier, and for gene therapy. The specific aims for the current funding period include: (1) clarifying the interactions between molecular umbrella- glutathione conjugates and phospholipid membranes, (2) characterizing the transport properties of molecular umbrella- glutathione conjugates, (3) defining the influence of cholesterol on the bilayer transport properties of a molecular umbrella- peptide conjugate, (4) defining the influence of facial hydrophilicity on membrane transport, (5) testing for "needle and thread" properties of molecular umbrella-oligoserine conjugates, (6) testing for "needle and thread" properties of a molecular umbrella-oligonucleotide conjugate, and (7) synthesizing molecular umbrella conjugates that can release biologically- active peptides in their free form. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen
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Project Title: MRP/GST SYNERGY IN MULTIDRUG RESISTANCE Principal Investigator & Institution: Morrow, Charles S.; Associate Professor; Biochemistry; Wake Forest University Health Sciences Winston-Salem, Nc 27157 Timing: Fiscal Year 2001; Project Start 10-MAY-1996; Project End 31-DEC-2004 Summary: The mechanisms involved in detoxification of drugs and poisons are important to cancer biology. The ability of a cell or tissue to detoxify xenobiotic poisons are associated with the emergence of anti-cancer drug resistance in tumors. In normal tissues, this detoxification activity influences the outcome of exposure to carcinogens and other toxins. A long term goal of the studies proposed is to understand the mechanisms by which the drug conjugating system, glutathione (GSH) and glutathione transferase (GST) and glutathione transferase (GST), and the toxin efflux transporters, MRP1 and MRP2, operate together to confer protection from anti-cancer drugs or carcinogens. This knowledge will improve the ability to predict the responses of particular tissues and tumors to toxin exposure including the risk of developing cancer in normal tissues or the likelihood of develop drug resistance in cancer. Moreover, this knowledge can be used to device more effect ant-cancer treatment or chemopreventive strategies. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen
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Project Title: NITRIC OXIDE AND HEPATIC FUNCTION IN SEPSIS AND TRAUMA Principal Investigator & Institution: Billiar, Timothy R.; Professor and Chairman; Surgery; University of Pittsburgh at Pittsburgh 350 Thackeray Hall Pittsburgh, Pa 15260 Timing: Fiscal Year 2001; Project Start 01-APR-1990; Project End 31-MAR-2003 Summary: The inducible nitric oxide synthase (iNOS) is upregulated diffusely during sepsis and clearly contributes to hemodynamic instability and organ injury during septic shock. However, in stark contrast to the damaging effects of iNOS in many tissues, in the liver upregulation of iNOS has a protective function. Sustained, high-level iNOS expression has no toxic effects on hepatocytes, and even low-level expression is protective. We now hypothesize that upregulation of iNOS in the liver during acute inflammatory states (i.e., sepsis) is part of a protective response that limits the toxicity of pro-inflammatory mediators, including TNFalpha. We have shown that NO can directly inhibit TNFalpha-induced signaling pathways leading to hepatocyte death. By activating soluble guanylate cyclase, NO inhibits the activation of the caspase cascade by TNFalpha, and via S-nitrosylation NO directly inhibits caspase protease activity. We have also shown that NO can regulate gene expression in hepatocytes to promote cell survival. We will now pursue the mechanistic basis of these observations in three aims. AIM I: To determine how NO/cGMP/G-kinase inhibits TNFalpha signaling in hepatocytes. Experiments under Aim I will define the level at which cGMP and the cGMP-dependent kinase inhibit TNFalpha signaling in hepatocytes. As part of this objective, we will identify the substrates for G-kinase that mediate the protective actions. AIM II: To determine the pathways leading to efficient S-nitrosylation of caspase in hepatocytes. Under Aim II, we will identify the factors that lead to efficient Snitrosylation of caspases in hepatocytes. Factors that are likely to be important and that will be tested include the levels of glutathione and intracellular iron as well as the ratio of NO to O2-. AIM III: To identify iNOS-induced protective genes in hepatocytes. Under Aim III, we will complete our analysis of NO-regulated genes in hepatocytes using differential display. We have already identified 11 candidate genes, and we will characterize genes that contribute to the hepatoprotective actions of iNOS. Upon completion of the three aims, it is expected that we will have an understanding of the factors that render hepatocytes less susceptible to injury and dysfunction during sepsis. By defining the protective mechanisms in hepatocytes, we will gain insights into the molecular mechanisms that lead to cellular toxicity in sepsis in susceptible organs. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen
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Project Title: NUCLEAR AND CYTOPLASMIC REDOX IN OXIDATIVE STRESS Principal Investigator & Institution: Jones, Dean P.; Professor; Biochemistry; Emory University 1784 North Decatur Road Atlanta, Ga 30322 Timing: Fiscal Year 2001; Project Start 01-SEP-2001; Project End 31-AUG-2006 Summary: (provided by applicant): Oxidative stress is an important component of toxicity due to environmental, occupational and therapeutic agents. Two major thiolcontaining defense systems exist to protect against oxidative stress, one utilizing the tripeptide glutathione (GSH) and the other using a small protein, thioredoxin (Trx). These systems have similar NADPH-dependent reductases and have overlapping functions and activities. However, there are also important differences, such as the role of thioredoxin in maintaining transcription factors in their reduced and functional forms. Although a considerable amount of information exists on the redox responses of the GSH system during redox signaling and oxidative stress, little information is
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available on the redox of Trx. The purpose of this proposal is to use a novel RedoxWestern blot technique to investigate the redox of Trx in cells, and use this in combination with cell fractionation to measure redox of the nuclear and cytoplasmic Trx pools. Redox of cellular GSH/GSSG and NADPH/NADP+ will be simultaneously determined to gain insight into the control and interaction of these redox pools. The first aim is to determine the redox state of nuclear and cytoplasmic Trx in HT29 cells during cell growth, differentiation and apoptosis. The second aim is to determine whether nuclear translocation of Nrf2, a transcription factor activated by oxidative stress and implicated in regulation of detoxification gene expression, is specifically associated with oxidation of cytoplasmic Trx redox while nuclear Trx remains reduced. The third aim is to selectively modify Trx redox in nuclear and cytoplasmic compartments to examine cause-effect relationships between Trx redox and transcriptional activation. This will be done with retroviral constructs containing mitochondrial Trx reductase in which the mitochondrial targeting sequence has been removed and a nuclear import or export signal has been added. Successful completion of these aims will quantitatively define the redox of nuclear and cytoplasmic Trx, show whether Trx and GSH have distinct functions in cell signaling and oxidative stress, and test whether nuclear or cytoplasmic Trx redox is critical in transcriptional activation during oxidant signaling. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •
Project Title: OXIDANT MECHANISMS IN NEONATAL BRAIN INJURY Principal Investigator & Institution: Ferriero, Donna M.; Professor; Neurology; University of California San Francisco 500 Parnassus Ave San Francisco, Ca 94122 Timing: Fiscal Year 2001; Project Start 01-APR-1996; Project End 31-AUG-2006 Summary: (provided by applicant): Recent data from our laboratory suggest that the developing brain responds differently to hypoxia-ischemia (H-I) than the mature brain, therefore requiring different strategies for neuroprotection. Our preliminary data suggest that the developing brain exposed to H-I is more susceptible than the adult brain to injury caused by free radicals, including nitric oxide and hydrogen peroxide. It is our hypothesis that the neonatal brain is more vulnerable than the mature brain because of a greater susceptibility to oxidative stress. This oxidative stress is due to hydrogen peroxide accumulation and sensitivity. To explore this hypothesis we will show that the immature brain accumulates more hydrogen peroxide than the mature brain after H-I, and that the maturity of the nervous system determines the differential responsivity. We will measure hydrogen peroxide accumulation in vivo and in vitro in response to H-I and correlate this with the location and type of cell death. Since the susceptibility to oxidative stress may be due to inadequate scavenging systems in the immature brain, we will measure glutathione peroxidase activity and localization and assess the effect of overexpression of this enzyme on neurological outcome. We will test whether differences in the regulation of glutathione levels and extent of oxidation between immature and mature brain account for differences in susceptibility to oxidative stress. We hypothesize that one mechanism for increased damage with hydrogen peroxide accumulation may be through the formation of hydroxyl ions as a result of the Fenton reaction. This mechanism is particularly important in the immature brain because of the increased amount of free iron. We will measure the localization and concentration of redox available iron and measure hydroxyl formation and outcome after iron chelation. The significance of the findings lies in the clinical application. Prenatal and perinatal hypoxia-ischemia are major causes of severe handicaps in neurologically impaired children. If blockade of free radicals can diminish perinatal H-I injury, development of specific inhibitors may lead to safe, easily administered therapies
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that could significantly reduce the burden for families and society in caring for these unfortunate children. The ability to identify therapies specific to the immature brain is of utmost importance and relevance to proper therapy. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •
Project Title: OXIDATIVE MECHANISMS IN CHROMIUM CARCINOGENESIS Principal Investigator & Institution: Sugden, Kent D.; Assistant Professor; Anthropology; University of Montana University Hall 202 Missoula, Mt 598124104 Timing: Fiscal Year 2001; Project Start 01-AUG-1999; Project End 31-JUL-2004 Summary: Chromium(VI) compounds pose a serious health risk to occupationally and environmentally exposed human populations. Exposure to Cr(VI) produces lung carcinomas in humans and laboratory animals. The overall objective of this research project is to elucidate the mechanism by which chromium(VI) compounds act as carcinogens. The hypotheses to be tested in this research project are: (1) that high valent +5 and +4 oxidation states of chromium are the primary intermediates that lead to oxidative DNA damage via direct DNA-metal interactions; (2) that reduction of Cr(VI) by intracellularly important reductants such as glutathione, ascorbate and cysteine form ligand-based radicals leading to oxidative DNA lesions but are of a lesser significance than oxidation by high valent chromium; (3) that these oxidative lesions are manifested in repair-deficient prokaryotic cell systems which are selectively sensitive to the DNA lesions detected in the in vitro studies. The specific aims of the proposed research are: (1) The mechanism of direct- or metal-centered oxidation of DNA by high valent chromium will be measured using model high valent Cr(V) compounds. Oxidation products arising from H-atom abstraction at the C1', C3', C4' and C5' of deoxyribose will be determined by HPLC and GC/MS using the model dinucleotide sugar oxidation substrate, 5',3'-di-O-Acetyl- d(TpT). Formation of guanine and cytosine base oxidation products will be determined using model dinucleotide substrates of d(GpG) and d(CpC). Base- and sequence-specificity of reactions with oligonucleotides will be determined by gel electrophoresis for formation of frank strand breaks and alkali-labile sites. The effect of aerobic vs anaerobic atmospheres will be determined on the above reactions. (2) The role of ligand-based radicals of glutathione, ascorbate and cysteine in the formation of DNA oxidation products will be probed by the specific (nonchromium) generation of these radical species and through their in situ formation by reduction with Cr(VI). The formation and fate of the radicals will be monitored by EPR. Measurement of sugar and base oxidation products as well as the formation of frank strand breaks and alkali-labile sites will be carried out as described in specific aim 1. (3) Selective lethality of Cr(VI) in DNA repair-deficient strains of E. coli will be determined. The synergistic effects of added ascorbate or modulation of intracellular glutathione levels will be determined. Transformation of a plasmid into the sensitive E. coli strains will be carried out for later extraction and measurement of base and sugar oxidation products and mutations. The proposed studies should give insight into the mechanisms of chromium(Vl)-induced DNA damage critical to the formation of cancer. Understanding these mechanisms may allow reduction of risk to exposed human populations. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen
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Project Title: OXIDATIVE STRESS AND BREAST CANCER RISK Principal Investigator & Institution: Gammon, Marilie D.; Professor; University of North Carolina Chapel Hill Office of Sponsored Research Chapel Hill, Nc 27599
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Timing: Fiscal Year 2001; Project Start 30-SEP-1992; Project End 31-JUL-2006 Summary: (provided by applicant): Reactive oxygen species derive from a number of different sources, and traditional and putative breast cancer risk factors can be linked to the disease by an oxidative stress mechanism, for example: 1) steroid hormones, as well as some environmental organochlorines, are metabolized to reactive quinones and hydroquinones, which can directly damage DNA; 2) the metabolism of alcohol results in production of ROS and damage to DNA; 3) BRCA1 is needed for post-transcriptional repair of oxidative damage, indicating that oxidative stress may be an important risk factor for women with a family history of the disease; and 4) the inverse relationship noted with consumption of fruits and vegetables could be related to their being a source of antioxidant vitamins. Also, several markers of oxidative stress in a number of studies were higher in women with breast cancer and those at high risk than among nondiseased women. Endogenous factors affect not only the generation of ROS, but also an antioxidant response to them. We propose that inter-individual variability in genes that encode enzymes with pro-oxidant and antioxidant activities will have an impact on the generation of ROS and ultimately on breast cancer risk. Furthermore, we hypothesize that risk associated with metabolic variability will be associated with exposure to exogenous factors that increase the likelihood of production of ROS. In this project, we propose to evaluate this hypothesis utilizing data from the Long Island Breast Cancer Study Project. DNA isolated from the blood samples donated by a large populationbased sample of breast cancer case and control women will be assayed for three different types of ROS-related genetic polymorphisms including: regulatory regions of enzymes or processes that generate ROS (myeloperoxidase and tumor necrosis factoralpha); those that prevent oxidative stress by neutralizing ROS (extracellular and manganese superoxide dismutase, glutathione peroxidase, catalase and glutathione Stransferase Mi); and those that will affect ultimate levels of ROS generated by the metabolism of steroid hormones (catechol O-methyltransferase, glucuronosyltransferase). In addition to the large number of subjects for whom samples are available for the laboratory analyses (n = 1087 cases and 1122 controls), comprehensive assessment of the subjects? environmental exposures has already been obtained in the parent study. Thus, we can also explore whether the genetic polymorphisms in ?at-risk? genotypes will affect associations between breast cancer risk and factors that are likely to be related through an oxidative stress mechanism, such as fruit and vegetable intake, reproductive and hormonal factors, alcohol consumption, and environmental contaminants (organochlorines and PAHs). Results from this project can be confirmed utilizing data from the Carolina Breast Cancer Study. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •
Project Title: FAILURE
OXIDATIVE
STRESS/ANTIOXIDANT
ENZYMES
IN HEART
Principal Investigator & Institution: Sam, Flora; Boston Medical Center Gambro Bldg, 2Nd Fl, 660 Harrison Ave, Ste a Boston, Ma 02118 Timing: Fiscal Year 2001; Project Start 01-AUG-2000; Project End 31-JUL-2005 Summary: The pathophysiology of heart failure remains incompletely understood. Recent evidence suggests that oxidative stress is increased in clinical heart failure (HF) and may contribute to the pathogenesis of left ventricular (LV) dysfunction. In vitro and in vivo animal studies indicate that reactive oxygen species (ROS) can exert direct myotoxic effects including impairment of contractility and cell death. In animal models of hemodynamic overload leading to heart failure, there is decreased antioxidant enzyme activity, and exogenous antioxidants have been shown to prevent the
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development of heart failure. The overall goal of this proposal is to determine the extent to which ROS in animal models contribute to the pathogenesis of human heart failure. In Specific Aim 1, we will test the hypothesis that oxidative stress is increased in the myocardium from patients with severe heart failure. Myocardial tissue samples will be obtained at the time of transplantation from patients with severe heart failure. Oxidative stress in the myocardium will be determined by measuring 8-isoprostane and the ratio of reduced/oxidized glutathione. In Specific Aim 2, we will test the hypothesis that there is decreased activity of antioxidant enzymes in the myocardium of patients with severe heart failure. In the myocardial tissue samples obtained for Aim 1, we will measure the activity and expression of superoxide dismutase, glutathione peroxidase and catalase. We will examine the extent to which changes in enzyme activity are due to changes in gene expression vs. post-translational modifications known to inhibit enzyme activity. In Specific Aim 3, we will test the hypothesis that systemic oxidative stress is increased in patients with systolic heart failure, and is associated with more rapid disease progression. In 100 patients with systolic LV dysfunction, followed in the Cardiomyopathy clinics at Boston Medical Center, we will measure 8-isoprostanes in the blood as a marker of systemic oxidative stress at baseline and annually for 3 years. We will correlate 8-isoprostanes with cardiac troponin I (cTn-I), a measure of ongoing myocardial damage and LV end-diastolic diameter by echocardiography (LVEDD), a measure of structural remodeling. In Specific Aim 4, we will test the hypothesis that polymorphisms of MnSOD, the major SOD in the myocardium, lead to increased oxidative stress and more rapid disease progression in patients with heart failure. In patients studied in Aim 3 we will determine the presence of the -9Ala/Val polymorphism of MnSOD that has been associated with reduced enzyme activity. The presence of this polymorphism will be correlated to 8- isoprostanes and remodeling markers from Aim 3. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •
Project Title: PHARMACOLOGY OF CYCLOPHOSPHAMIDE AND OTHER ALKYLATORS Principal Investigator & Institution: Colvin, Oliver M.; Professor; Medicine; Duke University Durham, Nc 27706 Timing: Fiscal Year 2001; Project Start 30-SEP-1977; Project End 31-JAN-2005 Summary: In this application we propose to continue our studies of the chemistry and pharmacology of cyclophosphamide and ifosfamide. The studies proposed focus on two critical aspects of the pharmacology of these agents, the definitive characterization of the DNA interstrand crosslinks produced by phosphoramide mustard and isophosphoramide mustard and the elucidation of the chemical and enzymatic determinants of the two P450 oxidations which determine the activation and inactivation of cyclophosphamide and ifosfamide. Our studies have demonstrated significant differences in the chemistry of phosphoramide mustard and isophophoramide mustard and in the interstrand crosslinks which will be produced by these molecules and their decomposition products. We have also recently discovered that acrolein produced from 4-hydroxycyclophosphamide gives O[6]-guanylate alkylation, probable crosslinking of DNA, and selects for resistance to BCNU by increased O[6]-alkyltransferase. We will explore the mechanisms of these reactions and determine if chloroacetaldehyde will produce similar effects. The repair of the demonstrated DNA crosslinks will be studied in our separately funded collaboration with Dr. Henry Friedman. We will also continue our studies of the P450 activation and dechlorethylation of cyclophosphamide and ifosfamide - determining the relative ratio
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of these reactions for different P450 enzymes, measuring deuterium isotope effects, defining the mechanism of the reactions, and examining the pharmacokinetic and antitumor properties of ifosfamide after altering the metabolism of ifosfamide by isotope and alkyl substitution induced kinetic switching of dechlorethylation to activation. We believe the results of these studies will have important implications for improving the clinical effectiveness of these important and unique antitumor agents. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •
Project Title: PILOT--MATERNAL ALCOHOL ABUSE AND ITS EFFECTS ON PREMATURE INFANTS Principal Investigator & Institution: Gauthier, Theresa W.; Emory University 1784 North Decatur Road Atlanta, Ga 30322 Timing: Fiscal Year 2003; Project Start 01-FEB-2003; Project End 31-DEC-2007 Summary: Despite the well known neurological effects of alcohol on the developing fetus, its use during pregnancy remains a significant problem in our country. Even with modern neonatal intensive care units, chronic lung disease and bacterial sepsis continue to cause significant morbidity and mortality for the very low birth weight premature newborn. We have expanded the traditional focus of fetal alcohol exposure on the central nervous system to two other developing organ systems of the fetus, namely the lung and immune system. Recent prospective data implicates a history of alcohol abuse as the first reported co-morbid variable significantly increasing the incidence and severity of acute respiratory distress syndrome in adults. Additionally, alcohol exposure is associated with a decrease in lung antioxidant status, particularly glutathione. Glutathione is an essential antioxidant in the epithelial lining fluid of the lung. A reduction in alveolar glutathione, as seen in the premature infant, leaves the lung susceptible to increased pulmonary oxidative injury. We have novel experimental data describing reduced pulmonary glutathione, impairment of alveolar type II epithelial cell function and impaired cell function and impaired surfactant homeostasis in fetal guinea pig lungs exposed to alcohol in utero. Additionally, in a logistic regression analysis of 872 term newborns, we have demonstrated that maternal excessive alcohol use of 7 drinks/wk in either the 3 months prior to conception of the 2nd trimester significantly increased the risk of newborn infection by approximately 3 fold. Because of these data implicating adverse effects of fetal alcohol exposure on the developing fetus, we hypothesize the following: (1) alcohol exposure in (CLD), and (2) fetal alcohol exposure impairs fetal immune function thereby increasing the risk of infection, particularly late onset sepsis, in the premature newborn. We will address these hypotheses in the pilot clinical study by 1: Screening all women who deliver premature infants weighing <1500 gms for alcohol use during pregnancy with an extensive questionnaire. 2: Perform outcome analysis of these infants comparing alcohol-exposed to non-exposed premature infants, investigating the primary outcomes of chronic lung disease and late onset sepsis. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen
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Project Title: PILOT--THE LUNG AS AN ETHANOL METABOLIZING ORGAN Principal Investigator & Institution: Polavarapu, Giri; Emory University 1784 North Decatur Road Atlanta, Ga 30322 Timing: Fiscal Year 2003; Project Start 01-FEB-2003; Project End 31-DEC-2007 Summary: This Center is focused on the mechanisms by which alcohol abuse produces chronic oxidative stress within the lung and renders it susceptibile to acute injury in
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response to insults such as sepsis and trauma. Studies in alcoholic liver disease demonstrate that ethanol is metabolized through phase I and phase II enzymes like alcohol dehydrogenase (ADH), aldehyde dehydrogenase (ALDH), and cytochrome P450EI, leading to accumulation of electrophiles, reactive oxygen species (ROS), and ultimately, oxidative stress. However, endogenous metabolism of ethanol and the subsequent oxidative stress within the lung has not been examined. We hypothesize that during chronic alcohol abuse, ethanol-metabolizing enzymes are induced within the lung and contribute to the oxidative stress and glutathione depletion that characterize the ?alcoholic lung'. In pilot experiments on rat lung tissue analyzed with state-of-theart Gene Chip technology, we determined that chronic ethanol ingestion increases expression of members of the alcohol, aldehyde dehydrogenases and P450 superfamilies (ADH I and IV, ALDH I & P4502EI). Ethanol-metabolizing enzyme induction correlated with levels of thiobarbituric acid reactive substances (TBARS), a marker of oxidative stress, and with induction of antioxidant enzymes including catalase, superoxide dismutase, and enzymes involved in glutathione homeostasis. Therefore, endogenous metabolism of ethanol within the lung may exert profound effects on lung function via mechanisms that are quite similar to its toxic effects in other tissues. To test this hypothesis we propose to first identify the specific isoforms of ADH, ALDH, cytochrome P4502EI, and catalase that are induced in the lung by chronic ethanol ingestion in rats using cytochemical, molecular biological, enzymatic and gene chip microarray methods. We will then study the regulation of selected phase II genes that are responsible for electrophile formation as well as ROS scavening, particularly within the alveolar epithelial microenvironment that our collaborators in this Center have shown to be a target of alcohol toxicity. Finally, based on our findings and collaborative studies with other investigators within the Center, we can use microarray technology to identify novel candidate genetic targets of alcohol abuse within the lung. Further, we can assess the potential therapeutic actions of treatments such as glutathione replacement and angiotensin II blockade that have been identified as a result of studies by our collaborators within the Center. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •
Project Title: POROUS GLASS-CERAMICS FOR PROTEIN PURIFICATION/ IMMOBILI Principal Investigator & Institution: Morgan, Steven H.; Fisk University Nashville, Tn 372083051 Timing: Fiscal Year 2001; Project Start 01-JUN-2001; Project End 31-MAY-2006 Summary: Glass-ceramics are polycystalline material prepared by the controlled crystallization of glass. Post-crystallization heat treatment and subsequent acid leaching of certain types of these glass-ceramics can produce porous materials which can be used as matrices for the purification and/or immobilization of biomolecules. Our goal in this proposal is to investigate the suitability of novel porous glass-ceramic matrices for purification and immobilization of proteins. The proposed research will focus initially on the CaO-TiO2-P205 system, and will subsequently be expanded to other glassceramic systems. The feasibility of forming thin- films of these porous glass-ceramics, which are important for biosensor applications, will also be investigated. The performance of these materials as matrices for protein purification will be assessed using the enzyme glutathione reductase (GSSGR). This project has three specific aims. (1) The first aim is to prepare and characterize a series of porous glass-ceramics in the calcium phosphate system. The effect of variations in composition, and postcrystallization processing on surface structure and chemistry will be investigated. To
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test the efficiency and compatibility of the newly developed porous glass- ceramics for purifying the enzymes from biological samples, we plan to use the enzyme glutathione reductase (GSSGR). (2) In addition to the calcium phosphate system, we also propose to investigate other glass ceramic systems. Initial candidates include silicate and silicophosphate glass-ceramics in which wollastonite and apattite crystal phases have been shown to nucleate near the surface of the glass. (3) The third aim of the project is to investigate the feasibility of forming thin-films of porous glass-ceramics, which could potentially have important applications in the field of biosensors. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •
Project Title: PREVENTING NIHL BY ENHANCING GLUTATHIONE PATHWAYS Principal Investigator & Institution: Kopke, Richard D.; Co-Director; U.S. Naval Medical Center (San Diego) 34800 Bob Wilson Dr (Cid) San Diego, Ca 92134 Timing: Fiscal Year 2001; Project Start 30-SEP-2001; Project End 31-JUL-2003 Summary: (provided by applicant): The primary objective of these studies is to test and develop pharmacologic agents to protect against noise-induced hearing loss (NIHL). The long-term objective is to develop agents for oral administration in clinical populations. The primary hypothesis is that pharmacologically optimizing the glutathione pathway will ameliorate or prevent NIHL and that this protection can be obtained by either injection or by oral administration of carefully selected glutathione enhancing agents. The secondary hypothesis is that noise exposure will alter the glutathione pathway as measured by the ratio of reduced to oxidized glutathione and the affiliated enzymes glutathione reductase (GR) and glutathione peroxidase (GSH-Px) during the first 6 hours of noise exposure and that these changes will correlate with the level of lipid peroxidation as measured by malondialdehyde (MDA) levels. The first specific aim is to determine the time course of any changes in the cochlear levels of reduced glutathione, and the ratio of reduced (GSH) vs. oxidized (GSSG) glutathione prior to noise exposure, and.5, 2, 4, and 6 hours after onset of noise exposure. This aim will be accomplished by measuring cochlear glutathione, both the reduced GSH and oxidized GSSG, in animals sacrificed at those times. The critical measures will be the reduced GSH, and the GSH/GSSG ratio, a measure of oxidative stress. The second specific aim is to determine the time course of any changes in cochlear GR and GSH-Px, critical enzymes of the glutathione anti-oxidant pathway, at those same times. The third specific aim is to determine the time course of changes in cochlear lipid peroxidation at those same times. The second and third aims will be accomplished by measuring GR, GSH-Px, and MDA, a marker for cell membrane oxidative damage, in animals sacrificed at those times. The fourth specific aim is to determine the efficacy of 3 putative otoprotective agents in reducing noise induced cochlear damage with auditory brainstem response thresholds and outer hair cell counts as primary measures. Protection efficacy will also be measured by GSH/GSSG, GR, GSH-Px, and MDA measures. The fifth specific aim is to compare the efficacy of these same agents orally administered to the IP administration, utilizing the same outcome measures. These studies should lay the basis for clinical trials of oral agents to prevent NIHL. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen
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Project Title: PROGNOSTIC MARKERS IN TRIALS FOR HEAD AND NECK CANCER Principal Investigator & Institution: Cullen, Kevin J.; Professor of Medicine, Oncology, and Oto; V T Lombardi Cancer Res Center; Georgetown University Washington, Dc 20057
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Glutathione
Timing: Fiscal Year 2003; Project Start 01-JUN-2003; Project End 31-MAY-2006 Summary: (provided by applicant): Our fundamental hypothesis is that readily identifiable biomarkers, including p53, thymidylate synthase and enzymes in the glutathione pathway are critical determinants of response and long term outcome for patients receiving chemotherapy and/or radiation for head and neck cancer. These biomarkers may be developed both as prognostic indicators to guide therapy and as targets for strategies which will enhance the efficacy of cisplatin based chemotherapy in this set of diseases. We present preliminary data which strongly suggest that overexpression of p53, thymidylate synthase and glutathione s-transferase (pi) are associated with poor outcome in patients receiving chemotherapy for head and neck cancer. We believe they can be developed as clinically important markers for patients with head and neck cancer. On the basis of our preliminary data, we propose the following aims: 1. To confirm the prognostic significance of p53, glutathione stransferase and thymidylate synthase in patients participating in clinical trials for head and neck cancer. 2. To confirm the prognostic significance of p53, glutathione stransferase and thymidylate synthase in a control group of patients receiving standard surgery and/or radiation therapy. 3. To develop tissue microarrays based on the samples in specific aims 1 and 2 for focused screening and validation of additional cellular factors as determinants of clinical response and outcome. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •
Project Title: PROTECTIVE EFFECTS OF SE FOLLOWING BENZO(A)PYRENE ADMIN IN CELL CULTURES (PILOT) Principal Investigator & Institution: Nyanda, Alfred M.; Meharry Medical College 1005D B Todd Blvd Nashville, Tn 37208 Timing: Fiscal Year 2003; Project Start 01-AUG-2003; Project End 31-JUL-2007 Summary: Benzo[a]pyrene [B(a)P] is one of the polycyclic aromatic hydrocarbons compounds that is formed during incomplete combustion of coal, gas, wood, and organic substances. This compound is a ubiquitous environmental pollutant, which is mutagenic and carcinogenic to both humans and animals. Many metabolites are formed dining the metabolism of B(a)P but (+/-)-benzo[a]pyrene-7,8-diol-9,10-epoxide is the most highly reactive one that binds with DNA and forms adducts at the N-7 guanine residue eventually leading to cellular transformation. Selenium may play a role in slowing this process of cellular transformation in vitro. Selenium has two major characteristics in that it is a mandatory component for the glutathione peroxidase scavenging process and also a necessary trace element and may potential be used as an adjunct treatment of many cancers such as breast cancer. Preliminary data from our lab suggest that selenium in moderate concentration (12.5 ppm) has an inhibitory effect on the growth of MDA-MB-435 breast cancer cells. The objective of this project is to chazactetize the anti-carcinogenic properties of selenium, by evaluating its effects on B(a)P treated cells. Therefore, the central hypothesis is that prior selenium treatment of 3T3 and CHO cells decreases the potential via the glutathione peroxidase pathway, to transform into malignant form subsequent to B(a)P exposure. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen
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Project Title: PROTEOMICS OF COMPLEX 1 INHIBITION IN GSH-DEPLETED CELLS Principal Investigator & Institution: Gibson, Bradford; Professor; Buck Institute for Age Research Novato, Ca 94945
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Timing: Fiscal Year 2003; Project Start 01-APR-2003; Project End 31-MAR-2005 Summary: (provided by applicant): Oxidative stress appears to play an important role in degeneration of dopaminergic neurons of the substantia nigra (SN) associated with Parkinson's disease (PD). The SN of early PD patients have dramatically decreased levels of the thiol tripeptide glutathione (GSH). GSH plays multiple roles in the nervous system both as an antioxidant and a redox modulator. Recently, we generated dopaminergic cell lines in which levels of GSH can be inducibly down-regulated via doxycycline (dox) induction of antisense messages against both the heavy and light subunits of gamma glutamyl cysteine synthetase (gamma-GCS), the rate-limiting enzyme in glutathione synthesis. Down-regulation of GCS results in reduction in mitochondrial GSH levels, increased oxidative stress, and decreased mitochondrial function. Interestingly, decreases in mitochondrial activities in GSH-depleted PC12 cells appears to be due to a selective inhibition of complex I activity similar to that observed in PD. This loss in enzymatic activity appears to be a result of cysteine oxidation which is reversible by the thiol-reducing agent dithiothreitol. These results suggest that early observed GSH losses in PD may be directly responsible for the noted decreases in complex I activity and the subsequent mitochondrial dysfunction which ultimately leads to dopaminergic cell death associated with the disease. The hypothesis we will examine in this proposal is that oxidation of specific cysteines within the protein subunits of mitochondrial complex I are responsible for the selective inhibition of its activity following GSH depletion. To accomplish this goal, we will employ a series of sulfhydryl-specific probes to assess the redox states of cysteine thiol groups in complex I proteins. We will use highly sensitive mass spectrometry-based proteomics methods to identify the cysteine residue(s) that are responsible for this reversible loss of mitochondrial complex I activity. We will also examine complex I proteins for other types of oxidative damage (both reversible and irreversible) that may contribute to this loss of activity. These data should provide valuable insight into the effect of oxidative stress on mitochondrial physiology as it relates to PD, particularly the structural basis for alterations in mitochondrial function. Knowledge of the molecular details of complex I dysfunction and the identification specific subunit(s) that are involved may point us towards novel therapeutic targets for the disease and provide key data on whether thiol replacement therapy is a viable option for treatment of the disease. Once identified, presence of these alterations will be assessed in future years in both an antiGSH transgenic mouse model of Parkinson disease as well as in Parkinsonian brains. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •
Project Title: REGULATION OF GLUTATHIONE SYNTHESIS IN OXIDATIVE STRESS Principal Investigator & Institution: Forman, Henry J.; Professor; Environmental Health Sciences; University of Alabama at Birmingham Uab Station Birmingham, Al 35294 Timing: Fiscal Year 2001; Project Start 15-APR-1996; Project End 31-MAR-2005 Summary: (Adapted from the Investigators abstract). This proposal focuses on the signal transduction mechanisms regulating the increase in de novo glutathione (GSH) synthesis that occurs during adaptation to oxidants and other electrophiles. GammaGlutamylcysteine synthetase (GCS), the rate limiting enzyme in de novo GSH synthesis, is composed of two subunits. Both GCS genes are transcriptionally up-regulated in response to stress from oxidants and electrophilic xenobiotics. Nonetheless, a mismatch between expression of the two GCS subunit proteins may result in altered kinetics and/or decreased stability of the enzyme. gamma-Glutamyl transpeptidase (GGT) is an exoenzyme that provides substrates for GSH synthesis by breaking down extracellular
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GSH. GGT enzymatic activity and mRNA transcription also increases in response to oxidants. While much has been learned over the past few years regarding mechanisms of GSH increases in adaptation, the signaling mechanisms that govern regulation of GCS and GGT on the transcriptional, post-transcriptional and post-translational levels remain largely unresolved. The investigators propose to test the following hypotheses in three aims: 1- that signaling for the transcriptional activation of GCS genes by electrophiles and H2O2-generating compounds occurs through overlapping pathways; 2- that the GCS regulatory subunit (GCS-LS) stabilizes the catalytic subunit against proteolysis as well as regulates the kinetics; 3- that GGT transcription by reactive oxygen species is mediated through activation specific signaling pathways and cis acting element(s) activated by H2O2. These hypotheses will be tested using the agents (2,3dimethoxy-1,4-naphthoquinone (DMNQ), 4-hydroxynonenal (4HNE), and betanaphthoflavone (BNF)) at concentrations and incubation times that cause increased transcription of both GCS subunits. Methods to be used include, dominant negative and constitutively active signaling components, kinase assays, in vivo footprinting, reporter construct, tetracycline regulated antisense transfection, and measurement of reactive oxygen species, glutathione oxidation and alpha-unsaturated aldehydes. These aims will be carried out by using established cell models modified as needed to determine whether the conclusions are unique or generally applicable. The long-range goal of their research is an understanding of the regulation of GSH synthesis and the potential for its pharmacological manipulation to enhance synthesis of this essential cellular constituent. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •
Project Title: REGULATION OF OXIDATIVE STRESS RESPONSE BY C-ABL AND ARG Principal Investigator & Institution: Kufe, Donald W.; Professor; Dana-Farber Cancer Institute 44 Binney St Boston, Ma 02115 Timing: Fiscal Year 2003; Project Start 28-FEB-2003; Project End 31-JAN-2008 Summary: (provided by applicant): Normal aerobic metabolism is associated with the generation of reactive oxygen species (ROS). Certain forms of ROS, such as hydrogen peroxide (H202), function as intracellular second messengers. ROS, however, also cause damage to DNA, proteins and lipids. Aerobic cells cope with the generation of potentially toxic ROS through antioxidant defense mechanisms. For example, catalase, a heme-containing peroxisomal enzyme, catalyzes the conversion of H202 to water and oxygen. H202 is also converted to water by cytosolic and mitochondrial glutathione peroxidase in a reaction which oxidizes glutathione. Despite the importance of these enzymes in controlling ROS, few insights are available regarding the regulation of catalase or glutathione peroxidase activity. Moreover, while failure of these and other antioxidant defenses to control ROS-induced damage is associated with apoptosis, little is known about the mechanisms that determine cell fate in response to oxidative stress.The c-Abl and related Arg nonreceptor tyrosine kinases are activated in the cellular response to oxidative stress. Activation of c-Abl is associated with targeting of cAbl to mitochondria, release of cytochrome c and induction of apoptosis. Activation of Arg contributes to ROS-induced apoptosis by a mechanism involving tyrosine phosphorylation of the pro-apoptotic Siva-1 protein. The finding that cells deficient in cAbl or Arg exhibit an attenuated apoptotic response to oxidative stress has supported a mechanism involving both proteins. Our hypothesis is that c-Abl and Arg form heterodimers in the ROS response and that this complex is of importance to the regulation of catalase and glutathione peroxidase. Moreover, our hypothesis is that, if these enzymatic antioxidant mechanisms are unable to control ROS-induced damage,
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then c-Abl and Arg function as a switch to signal apoptosis. The proposed studies will address these hypotheses and how c-Abl and Arg determine cell fate in the oxidative stress response. The Specific Aims are: 1) To further define the mechanisms responsible for activation of c-Abl and Arg signaling in response to oxidative stress; 2) To determine the role of c-Abl and Arg in the regulation of oxidative stress by catalase; 3) To assess the effects of c-Abl and Arg on activation of glutathione peroxidase; and 4) To define the downstream effectors of c-Abl and Arg in the apoptotic response to oxidative stress. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •
Project Title: ROLE OF GLUTATHIONE REDUCTASE AND MACROPHAGE ONCOSIS Principal Investigator & Institution: Asmis, Reto Hr.; Medicine; University of Kentucky 109 Kinkead Hall Lexington, Ky 40506 Timing: Fiscal Year 2002; Project Start 01-AUG-2002; Project End 31-JUL-2006 Summary: (provided by applicant): We hypothesize that increased glutathione reductase activity protects human macrophages from OxLDL-induced mitochondrial dysfunction and cell death, thereby decreasing the severity of atherosclerosis. Macrophage and foam cell death by oncosis plays a crucial role in the development of atherosclerotic lesions. We propose to study the molecular mechanism of glutathione reductase-mediated protection of macrophages from oncosis.Specific Aim 1: To determine the effect of OxLDL on the thiol redox state of mitochondria. Our preliminary data demonstrate that OxLDL induces mitochondrial depolarization and loss of ATP synthesis. We will use human monocyte-derived macrophages to determine if OxLDL promotes oncosis by 1) altering the thiol redox status of mitochondria, 2) inactivating mitochondrial glutathione reductase and 3) increasing mitochondrial inner membrane permeability.Specific Aim 2: To determine the role of mitochondrial and cytosolic glutathione reductase in preventing OxLDL-induced oncosis. Mitochondria do not synthesize glutathione (GSH) and therefore rely on GSH uptake and the reduction of GSSG to maintain the appropriate thiol redox state. We will use human monocytederived macrophages to determine 1) if adenovirus-mediated doxycycline-controlled expression of mitochondrial or cytosolic glutathione reductase (GR) prevents GSSG accumulation and protein thiol oxidation and 2) if increasing glutathione reductase activity restores mitochondrial function and protects macrophages from OxLDLinduced oncosis.Specific Aim 3: To determine whether increased macrophage glutathione reductase activity decreases the severity of atherosclerosis. Foam cell death promotes the formation of the necrotic core and the progression of atherosclerotic lesions. We will perform bone marrow transplantation studies to determine in vivo whether augmented expression of glutathione reductase (GR) in macrophages prevents foam cell death and lesion progression. GR-overexpressing bone marrow cells, generated by retroviral gene transfer, will be used to repopulate irradiated LDL receptor null mice and apoE null mice. We will measure both lesion size and lesional cholesterol/cholesterol ester content. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen
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Project Title: ROLE OF THE GLUTATHIONE SYSTEM IN CELL STRESS AND AGING Principal Investigator & Institution: Andersen, Julie; Assistant Professor; University of Southern California 2250 Alcazar Street, Csc-219 Los Angeles, Ca 90033 Timing: Fiscal Year 2002; Project Start 01-JUN-2002; Project End 31-MAY-2003
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Summary: A growing body of correlative evidence has implicated free radicals as a important factor in the pathology of both Parkinson's disease (PD) and normal brain aging. Dopaminergic nigrostriatal neurons, the predominant cell type lost in PD, are believed to be highly susceptible to free radical damage due to the propensity for dopamine to oxidize, producing elevated levels of reactive oxygen species. This problem is exacerbated by region-specific decreases in antioxidant defenses in the proximity of the substantia nigra. De-regulation of the glutathione system, a major component of the antioxidant defense system in the brain, has been strongly implicated as a causal factor in the resulting neuronal degeneration, but a direct role has yet to be definitively proved. We propose in this study to use genetic engineering to directly assess the involvement of the glutathione system in protecting the brain against neuronal damage due to either acute and chronic oxidative stress, and to test whether deregulation of this system can result in neurodegeneration like that seen in PD or during the normal aging process. This will be done using tissue culture and animal models in which levels of glutathione are altered by either over- or underexpression of glutamylcysteine synthase (GCS), the rate limiting enzyme in the synthesis of glutathione, or genetic over- or underexpression of glutathione peroxidase, the enzyme which acts with glutathione to de- toxicity reactive oxygen species. Such in vitro and in vivo systems should allow us to explore the hypothesis that genetic variations in levels of these molecules could be involved in predisposition to or protection against Parkinson's or neuronal degeneration during normal aging. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •
Project Title: SAME INHIBITS INFLAMMATORY-MEDIATED ENHANCED TOXICITY Principal Investigator & Institution: Maddox, Jane F.; Nat Food Safety & Toxicol Ctr; Michigan State University 301 Administration Bldg East Lansing, Mi 48824 Timing: Fiscal Year 2002; Project Start 30-SEP-2002; Project End 31-AUG-2004 Summary: (provided by applicant): Injury to hepatocytes by toxicants such as ethanol and allyl alcohol is a multi-faceted process, leading to cellular dysfunction and cell death via pathways that are not clearly defined. 80me of the mechanisms proposed to contribute include glutathione depletion and subsequent oxidant stress in the cell. In addition, these toxicants alone, or in combination with other agents, may induce the production of endogenous mediators that further damage hepatocytes. S-adenosyI-Lmethionine (SAMe) is a nutritional supplement that appears to have positive effects as a treatment for liver injury caused by hepatotoxicants, though its mechanisms of action are not clearly understood. SAMe is a methyl donor and a precursor for the antioxidant molecule glutathione. The intent of this proposal is to use allyl alcohol as a model for toxicant-induced hepatocyte injury, and determine the role of SAMe in attenuating the cellular damage. In addition, this laboratory has determined that allyl alcohol liver damage is augmented by the endogenous compound 15- deoxy-prostaglandin J2 (15dPGJ2). Allyl alcohol and 15d-PGJ2 are proposed to act in an additive manner to deplete glutathione and inhibit the activation of nuclear factor (NF) kB, leading to decreased production of survival proteins and hepatooyte death. The overall hypothesis to be tested is that SAMe inhibits allyl alcohol toxicity and 15d-PGJ2 augmentation of this toxicity via stabilizing glutathione levels and establishing an oxidant balance in the cell, thus maintaining healthy mitochondda and a normalized NFkB activation status. Subcellular localization (cytosol versus mitochondda versus nucleus) of glutathione depletion may be important in determining NFkB activation and cell fate. The following specific aims will be tested: 1) SAMe inhibits glutathione depletion by allyl alcohol and
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15d-PGJ2 in hepatocytes, thus decreasing cytotoxicity. 2) SAMe counteracts oxidative stress in hepatocytes due to GSH depletion caused by allyl alcohol and augmented by 15d-PGJ2, thereby maintaining a normalized NFKB activation status and decreasing cytotoxicity. 3) SAMe corrects hepatocyte mitochondrial dysfunction caused by allyl alcohol and 15d-PGJ2. 4) SAMe inhibits allyl alcohol and 15d-PGJ2-induced hepatocyte toxicity, whether cell death occurs via apoptotic or necrotic pathways. These experiments will give insight into the potential interaction of an endogenous product, 15d-PGJ2, in the complex relationship of toxicants, somatic response elements and therapeutic agents in determining liver health and cell survival. Results from these studies will increase our knowledge of the mechanism of action of an alternative medicine already in common use, SAMe, in countering the injurious actions of hepatotoxicants, with allyl alcohol as a model. Moreover, they may provide evidence for development of related therapeutic compounds. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •
Project Title: SIGNAL TRANSDUCTION IN CYTOPROTECTIVE RESPONSES Principal Investigator & Institution: Iordanov, Mihail; Cell and Developmental Biology; Oregon Health & Science University Portland, or 972393098 Timing: Fiscal Year 2002; Project Start 01-APR-2002; Project End 31-MAR-2007 Summary: (PROVIDED BY APPLICANT) Electrophilic compounds exert cellular toxicity by compromising the redox balance of cells and causing oxidative stress. Relevant examples of such compounds are environmental pollutants such as AS3+ and Cd2+, products of the peroxidation of fatty acids, such as 4-hydroxy-2,3-nonenal, and chemotherapeutic agents, such as doxorubicin. The phase II detoxifying enzymes (a group of conjugating enzymes that includes, among others, glutathione S-transferases and quinone reductases) are the major cellular defense system against toxic environmental and metabolic electrophiles. Investigating the anti-oxidant response of mouse embryonic fibroblasts deficient in the genes encoding the stress-activated protein kinases JNK1 and JNK2, we have found that, like phase II detoxifying enzymes, JNKs are critical for the cytoprotective responses to electrophiles and oxidants. JNK-deficient cells are severely susceptible to oxidative stress and this increased susceptibility correlates with elevated production of reactive oxygen species by JNK-deficient cells and their inability to maintain sufficient levels of several phase II detoxification enzymes (e.g. the glutathione S-transferases of the A, M, and P functional classes) when challenged with electrophiles and oxidants. The research proposed in this grant proposal will elucidate the molecular mechanisms that mediate the regulation of phase II enzyme expression by JNK and the involvement of these JNK-regulated phase II enzymes in the resistance to environmental oxidants and electrophiles. To this end, we will utilize fibroblast cells from mice with genetic inactivation ("knockout") of JNKs and various upstream regulators of JNK activity and we will employ molecular, cellular, and biochemical approaches (such as transfection, inducible expression of transgenic alleles, site-directed mutagenesis, analysis of gene expression at mRNA and protein levels, analysis of post-translational protein modifications, subcellular fractionation, and pharmacological interference with enzyme functions). The proposed research may lead to the development (on the basis of pharmacological effectors of the JNK signaling pathway) of novel strategies for counteracting the harmful pro-oxidant impact of important environmental pollutants. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen
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Project Title: SIGNIFICANCE OF GGT EXPRESSION IN TUMORS Principal Investigator & Institution: Hanigan, Marie H.; Associate Professor; Cell Biology; University of Oklahoma Hlth Sciences Ctr Health Sciences Center Oklahoma City, Ok 73126 Timing: Fiscal Year 2001; Project Start 01-AUG-1992; Project End 31-MAR-2003 Summary: (adapted verbatim from the investigator's abstract) Cisplatin is the most effective chemotherapy drug for the treatment of ovarian cancer. Its usefulness in the clinic is restricted by dose-limiting nephrotoxicity and the development of drugresistance within the tumor. During the previous funding period our studies demonstrated that the nephrotoxicity of cisplatin is due to the metabolism of cisplatinglutathione conjugate through a GGT- mediated pathway in the kidney. We further demonstrated that this GGT-mediated toxicity is specific to the kidney. When GGT was transfected into tumor cells it reduced the toxicity of cisplatin rather than increasing it as was seen in the kidney. These findings indicate that there are two distinct mechanisms of cisplatin toxicity. The delineation of these two mechanisms would provide the opportunity to inhibit the side effects of cisplatin without compromising its antitumor activity. The current proposal focuses on defining the mechanisms by which cisplatin exerts its toxic effects and identifying the mechanism by which tumor cells develop resistance to cisplatin. The first specific aim is to further characterize the unstable cisplatin-glutathione conjugate that is a substrate for GGT and follow its metabolism within the kidney. A series of cisplatin-glutathione conjugates will be tested as substrates for GGT-mediated activation to nephrotoxins by LLC-PK1 cells and human renal proximal tubule cells. Cisplatin-glutathione conjugates will be isolated by HPLC and their structure determined by Mass Spectrometry. The pathway by which they are metabolized will be determined with the use of selective inhibitors of enzymes within the pathways. Inhibitors that block the activation of cisplatin in vitro will be tested for their ability to block the nephrotoxicity of cisplatin in vivo. The second specific aim is to identify the mechanism by which tumors become resistant to cisplatin in vivo. Human epithelial ovarian tumors will be propagated in nude mice. Half the mice will be treated with cisplatin. Cisplatin resistant tumors will be isolated after several courses of treatment. mRNA will be isolated from these tumors and differentially expressed genes will be isolated by representational differential analysis. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen
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Project Title: SPECIES DIFFERENCE IN THE BIOTRANSFORMATION OF AFLATOXIN Principal Investigator & Institution: Eaton, David L.; Professor and Associate Dean; Environmental Health; University of Washington Seattle, Wa 98195 Timing: Fiscal Year 2001; Project Start 01-MAY-1991; Project End 31-JUL-2004 Summary: Numerous studies have demonstrated that biologically active, natural components of the diet may confer resistance to chemical carcinogens via induction and/or inhibition of biotransformation enzymes. In particular, specific chemical components of the diet, such as flavonoids, isocyanates, glucosinolates, indoles, dithiolthiones, and polyphenols have been identified as effective inducers and/or inhibitors of carcinogen activation/detoxification pathways in animal models. There is much supporting data from human epidemiological studies on the important relationship between diet and cancer in humans, although the diversity and complexity of the diet, and uncertainty of specific exposures, in such studies makes identification of specific active components nearly impossible. Although animal models are useful for
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"hypothesis testing", species differences in carcinogen activation and detoxification pathways, as well as differences in gene regulation and expression in response to inducers, make extrapolation of animal data to the human situation tentative, at best. Thus, there is a need to develop model systems that utilize human cells/tissues to determine the efficacy of specific dietary components and/or putative chemoprotectant drugs to favorably modify the biotransformation of human carcinogens. One such model human carcinogen is aflatoxin B1. Aflatoxins are mycotoxins produced by the common fungal molds, Aspergillus flavus and Aspergillus parasiticus. Worldwide, aflatoxins are considered a major public health problem because of their potent carcinogenic effects. Human epidemiological data has documented that humans are susceptible to AFB-induced hepatocarcinogenesis, especially in combination with hepatitis B virus infection. However, there are large species differences in the susceptibility to aflatoxin carcinogenesis. Rats are highly sensitive, whereas mice are very resistant. The mechanism for this difference is associated with the expression of a specific enzyme, glutathione S-transferase A3-3 (mGSTA3-3), which is present in the livers of mice, but not rats. Treatment of rats with the drug, oltipraz, or the food additive, ethoxyquin, protects rats from aflatoxin-induced liver cancer. The mechanism for this protection is due to the ability of these chemicals to "turn on" a gene for a glutathione S-transferase, rGSTA5-5, that is normally not expressed in rat liver, but which efficiently detoxifies aflatoxin. Human liver tissue has very low ability to detoxify aflatoxin -- in fact, worse than the poor ability of rats. There has been considerable interest in devising a dietary or chemointervention strategy for humans that increases resistance to AFB by induction of GSTs. The long range goals of this proposal are to: 1) establish in vitro models that utilize isolated human hepatocytes in culture and human cDNA expressing yeast, to assess the efficacy of specific dietary components as putative chemoprotectors against AFB and other chemical carcinogens, and 2) complete the characterization of species differences in glutathione S-transferases with activity toward AFB-epoxide. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •
Project Title: THE NEUROPROTECTIVE EFFECT OF TETRAHYDROBIOPTERIN Principal Investigator & Institution: Kang, Un Jung.; Associate Professor; Neurology; University of Chicago 5801 S Ellis Ave Chicago, Il 60637 Timing: Fiscal Year 2003; Project Start 01-APR-2003; Project End 31-MAR-2008 Summary: (provided by applicant): While multiple etiologies are likely to account for Parkinson's disease (PD), the core pathogenic feature is degeneration of dopaminergic neurons, particularly those in the substantia nigra pars compacta (SNpc), with shared common final pathways involving oxidative damage, mitochondrial dysfunction, or both. Therefore, one may hypothesize that dopaminergic neurons in the SNpc are selectively vulnerable to oxidative stresses and/or mitochondrial disruption and understanding the mechanism of this selectivity may reveal the pathogenesis. However, our data show that ventral mesencephalic dopaminergic neurons in culture have an enhanced antioxidant capacity, as they are better able to resist oxidative stresses such as glutathione depletion and peroxide treatment than nondopaminergic neurons. In addition, their enhanced antioxidant capacity is reflected in lower reactive oxygen species (ROS) and higher reduced glutathione levels than nondopaminergic neurons. We hypothesize that an enhanced antioxidant capacity is essential for the survival of dopaminergic neurons that may be subjected to increased oxidative stress exerted by dopamine and its metabolites. We postulate that disruption of this innate antioxidant capacity makes them vulnerable to additional environmental insults and thereby leads
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to selective degeneration. We noted that the enhanced antioxidant capacity in ventral mesencephalic dopaminergic neurons is due to tetrahydrobiopterin (BH4), which is the cofactor for tyrosine hydroxylase, the enzyme producing dopamine, but also lowers superoxide levels, partly be direct scavenging effect and modulates mitochondrial function. First, We will study the effect of BH4 on mitochondrial bioenergetics and function including initiation of death pathways. Second, we will examine the role of BH4 on NO and superoxide generation and in modulating other endogenous antioxidant systems. Third, the neuroprotective function of BH4 against PD models such as 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine, rotenone toxicity, and glutathione depletion will be tested in vivo and in organotypic slice cultures, using hph-1 mice that are deficient in BH4, production. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •
Project Title: UP-REGULATION OF K+ CHANNELS IN THE REMODELED VENTRICLE Principal Investigator & Institution: Rozanski, George J.; Associate Professor; Physiology and Biophysics; University of Nebraska Medical Center Omaha, Ne 681987835 Timing: Fiscal Year 2001; Project Start 30-SEP-2000; Project End 31-AUG-2004 Summary: Electrical remodeling of the heart predisposes to arrhythmias which largely account for the high incidence of morbidity and mortality in patients with chronic cardiac disorders. It is postulated that down-regulation of K+ currents, particularly the transient outward current, Ito, contributes to this increased risk of arrhythmogenesis via repolarization abnormalities. This project will explore the endogenous redox buffer glutathione as an antiarrhythmic intermediate that up-regulates Ito channel activity in the electrically remodeled ventricle. Our studies will test the central hypothesis that down-regulation of Ito in the remodeled ventricle is mediated by a reversible decrease in myocyte redox state by addressing three specific aims: (1) to determine the impact of glutathione precursors on redox state and Ito in myocytes from the remodeled ventricle, (2) to determine if metabolic control of Ito via glucose utilization is mediated by alterations in glutathione, and (3) to determine if glutathione modulators increase expression of Ito channels in the remodeled ventricle. We will conduct studies on isolated ventricular myocytes from rat hearts undergoing remodeling due to chronic myocardial infarction or hypertension. The patch-clamp technique will be used to record action potentials, as well as whole-cell and single channel currents in myocytes treated with pharmacologic modulators of glutathione. Changes in glutathione redox state, measured by an HPLC- fluorescent labeling technique, will be correlated with electrophysiological properties and the expression of the major channel isoforms underlying Ito, Kv4.2 and Kv4.3, by immunoblotting of channel protein. Changes in steady- state levels of channel mRNA will also be determined by semi-quantitative RTPCR. We propose that these experiments will identify endogenous pathways that may be effective therapeutic targets to correct or prevent arrhythmias in the remodeled heart. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen
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Project Title: WHAT IS THE METABOLIC FUNCTION OF SELENOPROTEIN W? Principal Investigator & Institution: Whanger, Philip D.; Professor; Environ & Molecular Toxicology; Oregon State University Corvallis, or 973391086 Timing: Fiscal Year 2001; Project Start 01-JUN-1999; Project End 31-MAY-2004 Summary: The function of selenoprotein W is unknown but is a selenocysteine containing protein, with highest concentrations in muscle, testes and brain. Selenium
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deficiency is associated with a failure to incorporate selenium into this protein, suggesting a critical metabolic role for it. Information on the function of selenoprotein W will be sought with knockout mice. Based on the genomic sequence, a knockout vector will be designed for injection into embryonic stem cells. After established procedures have been used to produce chimeric mice, they will be bred to normal mice to obtain heterozygotes. These will be used in selected breeding to obtain homozygotes which should lack the gene for selenoprotein W. Southern blots will be used to determine if the desired animals have been obtained. Experiments are planned to determine if the knockout mice are more subject to peroxidation, using three different compounds to promote this disorder. The effects of selenoprotein W deletion on the expression of other selenoproteins such as the cellular glutathione peroxidase (GPX1) and the phospholipid hydroperoxidase (GPX4) will be examined in these knockout mice. The knockout mice will be given selenium to show that this element will increase the activities of GPX1 and GPX4 but not selenoprotein W. This will be followed by oxidative stress studies with tissue cultures of muscle cells to confirm the results in the whole animal. Glutathione and a smaller adduct are stoichiometrically bound to selenoprotein W from muscle, and the identification and binding of this small adduct to selenoprotein W will be explored as a means of further investigation into its metabolic function. We have access to knockout mice deficient in gamma-glutamyl transpeptidase and these will be used to determine the effects of altered glutathione and cystine levels on selenoprotein W content. These animals will also be supplemented with selenium to determine the effects upon selenoprotein W and GPX1 and GPX4 induction. 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 “glutathione” (or synonyms) into the search box. This search gives you access to full-text articles. The following is a sample of items found for glutathione in the PubMed Central database: •
"Enzymogenesis": Classical Liver Alcohol Dehydrogenase Origin from the Glutathione-Dependent Formaldehyde Dehydrogenase Line. by Danielsson O, Jornvall H.; 1992 Oct 1; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&rendertype=abstr act&artid=50103
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1-Chloro-2,4-Dinitrobenzene-Elicited Increase in Vacuolar Glutathione-S-Conjugate Transport Activity. by Li ZS, Zhen RG, Rea PA.; 1995 Sep; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&rendertype=abstr act&artid=157574
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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 cadmium-sensitive, glutathione-deficient mutant of Arabidopsis thaliana. by Howden R, Andersen CR, Goldsbrough PB, Cobbett CS.; 1995 Apr; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&rendertype=abstr act&artid=157238
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A Gene from Aspergillus nidulans with Similarity to URE2 of Saccharomyces cerevisiae Encodes a Glutathione S-Transferase Which Contributes to Heavy Metal and Xenobiotic Resistance. by Fraser JA, Davis MA, Hynes MJ.; 2002 Jun; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=123945
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A Genomics Approach to the Comprehensive Analysis of the Glutathione STransferase Gene Family in Soybean and Maize. by McGonigle B, Keeler SJ, Lau SM, Koeppe MK, O'Keefe DP.; 2000 Nov 1; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=59210
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A Glutathione Conjugate of Hepoxilin A3: Formation and Action in the Rat Central Nervous System. by Pace-Asciak CR, Laneuville O, Su W, Corey EJ, Gurevich N, Wu P, Carlen PL.; 1990 Apr 15; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&rendertype=abstr act&artid=53829
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A Glutathione S-Transferase with Activity towards cis-1,2-Dichloroepoxyethane Is Involved in Isoprene Utilization by Rhodococcus sp. Strain AD45. by van Hylckama Vlieg JE, Kingma J, van den Wijngaard AJ, Janssen DB.; 1998 Aug; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=106775
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A Medicago truncatula Homoglutathione Synthetase Is Derived from Glutathione Synthetase by Gene Duplication. by Frendo P, Jimenez MJ, Mathieu C, Duret L, Gallesi D, Van de Sype G, Herouart D, Puppo A.; 2001 Aug 1; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=117169
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A Peptide Permease Mutant of Mycobacterium bovis BCG Resistant to the Toxic Peptides Glutathione and S-Nitrosoglutathione. by Green RM, Seth A, Connell ND.; 2000 Feb; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=97159
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A role for glutathione peroxidase in protecting pancreatic [beta] cells against oxidative stress in a model of glucose toxicity. by Tanaka Y, Tran PO, Harmon J, Robertson RP.; 2002 Sep 17; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=129450
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A soluble auxin-binding protein from Hyoscyamus muticus is a glutathione Stransferase. by Bilang J, Macdonald H, King PJ, Sturm A.; 1993 May; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&rendertype=abstr act&artid=158743
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Alternate Energy-Dependent Pathways for the Vacuolar Uptake of Glucose and Glutathione Conjugates. by Bartholomew DM, Van Dyk DE, Lau SM, O'Keefe DP, Rea PA, Viitanen PV.; 2002 Nov 1; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=166675
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Amino Acid Sequence of Rat Kidney Glutathione Synthetase. by Huang C, He W, Meister A, Anderson ME.; 1995 Feb 14; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&rendertype=abstr act&artid=42673
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An ATP-Dependent As(III)-Glutathione Transport System in Membrane Vesicles of Leishmania tarentolae. by Dey S, Ouellette M, Lightbody J, Papadopoulou B, Rosen BP.; 1996 Mar 5; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&rendertype=abstr act&artid=39933
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An Ethylene-Responsive Enhancer Element is Involved in the Senescence-Related Expression of the Carnation Glutathione-S-Transferase (GST1) Gene. by Itzhaki H, Maxson JM, Woodson WR.; 1994 Sep 13; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&rendertype=abstr act&artid=44719
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AN9, a Petunia Glutathione S-Transferase Required for Anthocyanin Sequestration, Is a Flavonoid-Binding Protein. by Mueller LA, Goodman CD, Silady RA, Walbot V.; 2000 Aug 1; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=59113
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Antioxidant Response to NaCl Stress in a Control and an NaCl-Tolerant Cotton Cell Line Grown in the Presence of Paraquat, Buthionine Sulfoximine, and Exogenous Glutathione. by Gossett DR, Banks SW, Millhollon EP, Lucas MC.; 1996 Oct; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&rendertype=abstr act&artid=158005
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Antisense Suppression of 2-Cysteine Peroxiredoxin in Arabidopsis Specifically Enhances the Activities and Expression of Enzymes Associated with Ascorbate Metabolism But Not Glutathione Metabolism. by Baier M, Noctor G, Foyer CH, Dietz KJ.; 2000 Oct 1; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=59186
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Ascorbic Acid Prevents Oxidative Stress in Glutathione-Deficient Mice: Effects on Lung Type 2 Cell Lamellar Bodies, Lung Surfactant, and Skeletal Muscle. by Jain A, Martensson J, Mehta T, Krauss AN, Auld PA, Meister A.; 1992 Jun 1; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&rendertype=abstr act&artid=49235
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AtMRP1 gene of Arabidopsis encodes a glutathione S-conjugate pump: Isolation and functional definition of a plant ATP-binding cassette transporter gene. by Lu YP, Li ZS, Rea PA.; 1997 Jul 22; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=21588
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AtMRP2, an Arabidopsis ATP binding cassette transporter able to transport glutathione S-conjugates and chlorophyll catabolites: functional comparisons with Atmrp1. by Lu YP, Li ZS, Drozdowicz YM, Hortensteiner S, Martinoia E, Rea PA.; 1998 Feb; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&rendertype=abstr act&artid=143980
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Augmentation of Glutathione in the Fluid Lining the Epithelium of the Lower Respiratory Tract by Directly Administering Glutathione Aerosol. by Buhl R, Vogelmeier C, Critenden M, Hubbard RC, Hoyt RF Jr, Wilson EM, Cantin AM, Crystal RG.; 1990 Jun 1; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&rendertype=abstr act&artid=54047
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Bacterial glutathione S-transferases: what are they good for? by Vuilleumier S.; 1997 Mar; http://www.pubmedcentral.gov/picrender.fcgi?tool=pmcentrez&action=stream&blobt ype=pdf&artid=178850
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Bacterial glutathione: a sacrificial defense against chlorine compounds. by Chesney JA, Eaton JW, Mahoney JR Jr.; 1996 Apr; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&rendertype=abstr act&artid=177915
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Bcl-2 expression causes redistribution of glutathione to the nucleus. by Voehringer DW, McConkey DJ, McDonnell TJ, Brisbay S, Meyn RE.; 1998 Mar 17; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=19676
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Blood glutathione synthesis rates in healthy adults receiving a sulfur amino acid-free diet. by Lyons J, Rauh-Pfeiffer A, Yu YM, Lu XM, Zurakowski D, Tompkins RG, Ajami AM, Young VR, Castillo L.; 2000 May 9; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=25783
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Chloroplast Transcription at Different Light Intensities. Glutathione-Mediated Phosphorylation of the Major RNA Polymerase Involved in Redox-Regulated Organellar Gene Expression. by Baena-Gonzalez E, Baginsky S, Mulo P, Summer H, Aro EM, Link G.; 2001 Nov 1; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=129274
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Cloning of a [mu]-Class Glutathione S-Transferase Gene and Identification of the Glucocorticoid Regulatory Domains in its 5' Flanking Sequence. by Fan W, Trifiletti R, Cooper T, Norris JS.; 1992 Jul 1; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&rendertype=abstr act&artid=49446
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Cloning, Expression, and Characterization of a Class-Mu Glutathione Transferase from Human Muscle, the Product of the GST4 Locus. by Vorachek WR, Pearson WR, Rule GS.; 1991 May 15; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&rendertype=abstr act&artid=51676
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Cold-hardiness-specific glutathione reductase isozymes in red spruce. Thermal dependence of kinetic parameters and possible regulatory mechanisms. by Hausladen A, Alscher RG.; 1994 May; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&rendertype=abstr act&artid=159348
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Construction, Expression, and Immunogenicity of the Schistosoma mansoni P28 Glutathione S-Transferase as a Genetic Fusion to Tetanus Toxin Fragment C in a Live Aro Attenuated Vaccine Strain of Salmonella. by Khan CM, Villarreal-Ramos B, Pierce RJ, Riveau G, Hormaeche RD, McNeill H, Ali T, Fairweather N, Chatfield S, Capron A, Dougan G, Hormaeche CE.; 1994 Nov 8; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&rendertype=abstr act&artid=45207
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Cr(III)-mediated crosslinks of glutathione or amino acids to the DNA phosphate backbone are mutagenic in human cells. by Voitkun V, Zhitkovich A, Costa M.; 1998 Apr 15; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&rendertype=abstr act&artid=147496
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Cytidine Methylation of Regulatory Sequences Near the [pi]-Class Glutathione STransferase Gene Accompanies Human Prostatic Carcinogenesis. by Lee W, Morton RA, Epstein JI, Brooks JD, Campbell PA, Bova GS, Hsieh W, Isaacs WB, Nelson WG.; 1994 Nov 22; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&rendertype=abstr act&artid=45306
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Dehalogenation of Dichloromethane by Dichloromethane Dehalogenase/Glutathione S-Transferase Leads to Formation of DNA Adducts. by Kayser MF, Vuilleumier S.; 2001 Sep 1; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=95400
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Demonstration of Nuclear Compartmentalization of Glutathione in Hepatocytes. by Bellomo G, Vairetti M, Stivala L, Mirabelli F, Richelmi P, Orrenius S.; 1992 May 15; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&rendertype=abstr act&artid=49092
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Detoxication of Base Propenals and Other [alpha],[beta]-Unsaturated Aldehyde Products of Radical Reactions and Lipid Peroxidation by Human Glutathione Transferases. by Berhane K, Widersten M, Engstrom A, Kozarich JW, Mannervik B.; 1994 Feb 15; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&rendertype=abstr act&artid=43183
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Differential induction of distinct glutathione-S-transferases of wheat by xenobiotics and by pathogen attack. by Mauch F, Dudler R.; 1993 Aug; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&rendertype=abstr act&artid=158905
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Dissecting the Superoxide Dismutase-Ascorbate-Glutathione-Pathway in Chloroplasts by Metabolic Modeling. Computer Simulations as a Step towards Flux Analysis. by Polle A.; 2001 May 1; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=102317
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Drosophila Glutathione S-Transferase 1-1 Shares a Region of Sequence Homology with the Maize Glutathione S-Transferase III. by Toung YS, Hsieh T, Tu CD.; 1990 Jan 1; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&rendertype=abstr act&artid=53193
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Early H2O2 Accumulation in Mesophyll Cells Leads to Induction of Glutathione during the Hyper-Sensitive Response in the Barley-Powdery Mildew Interaction. by Vanacker H, Carver TL, Foyer CH.; 2000 Aug 1; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=59088
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Engineering the Substrate Specificity of Glutathione Reductase Toward that of Trypanothione Reduction. by Henderson GB, Murgolo NJ, Kuriyan J, Osapay K, Kominos D, Berry A, Scrutton NS, Hinchliffe NW, Perham RN, Cerami A.; 1991 Oct 1; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&rendertype=abstr act&artid=52591
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Equilibrium and Kinetic Constants for the Thiol-Disulfide Interchange Reaction between Glutathione and Dithiothreitol. by Rothwarf DM, Scheraga HA.; 1992 Sep 1; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&rendertype=abstr act&artid=49831
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Escherichia coli Resistance to Chlorine and Glutathione Synthesis in Response to Oxygenation and Starvation. by Saby S, Leroy P, Block JC.; 1999 Dec; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=91765
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Evidence for the Presence of the Ascorbate-Glutathione Cycle in Mitochondria and Peroxisomes of Pea Leaves. by Jimenez A, Hernandez JA, Del Rio LA, Sevilla F.; 1997 May; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&rendertype=abstr act&artid=158303
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Exogenous Glutathione Completes the Defense against Oxidative Stress in Haemophilus influenzae. by Vergauwen B, Pauwels F, Vaneechoutte M, Van Beeumen JJ.; 2003 Mar; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=148052
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Expression and characterization of glutathione peroxidase activity in the human blood fluke Schistosoma mansoni. by Mei H, Thakur A, Schwartz J, Lo Verde PT.; 1996 Oct; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&rendertype=abstr act&artid=174370
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Expression and RNA splicing of the maize glutathione S-transferase Bronze2 gene is regulated by cadmium and other stresses. by Marrs KA, Walbot V.; 1997 Jan; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&rendertype=abstr act&artid=158119
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Expression Cloning of a cDNA for Human Leukotriene C4 Synthase, an Integral Membrane Protein Conjugating Reduced Glutathione to Leukotriene A4. by Lam BK, Penrose JF, Freeman GJ, Austen KF.; 1994 Aug 2; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&rendertype=abstr act&artid=44462
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Expression Cloning of the cDNA for a Polypeptide Associated with Rat Hepatic Sinusoidal Reduced Glutathione Transport: Characteristics and Comparison with the Canalicular Transporter. by Yi J, Lu S, Fernandez-Checa J, Kaplowitz N.; 1995 Feb 28; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&rendertype=abstr act&artid=42546
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Expression of a Schistosoma mansoni 28-kilodalton glutathione S-transferase in the livers of transgenic mice and its effect on parasite infection. by Xu X, Lemaire C, Grzych JM, Pierce RJ, Raccurt M, Mullier F, Zerimech F, Decavel JP, Peyrol S, Liu J, Fontaine J, Lafitte S, Capron A, Cesbron JY.; 1997 Sep; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&rendertype=abstr act&artid=175552
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Expression of Catalytically Active Barley Glutamyl tRNAGlu Reductase in Escherichia coli as a Fusion Protein with Glutathione S-Transferase. by Vothknecht UC, Kannangara CG, Wettstein DV.; 1996 Aug 20; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&rendertype=abstr act&artid=38634
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Expression of Mammalian Glutathione S-Transferase 5-5 in Salmonella typhimurium TA1535 Leads to Base-Pair Mutations Upon Exposure to Dihalomethanes. by Thier R, Taylor JB, Pemble SE, Humphreys WG, Persmark M, Ketterer B, Guengerich FP.; 1993 Sep 15; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&rendertype=abstr act&artid=47400
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Expression of Recombinant Glutathione S-Transferase [pi], Ya, or Yb1 Confers Resistance to Alkylating Agents. by Puchalski RB, Fahl WE.; 1990 Apr 1; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&rendertype=abstr act&artid=53705
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Expression of Two Glutathione S-Transferase Genes in the Yeast Issatchenkia orientalis Is Induced by o-Dinitrobenzene during Cell Growth Arrest. by Tamaki H, Yamamoto K, Kumagai H.; 1999 May 1; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=93744
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Forced Evolution of Glutathione S-Transferase to Create a More Efficient Drug Detoxication Enzyme. by Gulick AM, Fahl WE.; 1995 Aug 29; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&rendertype=abstr act&artid=41111
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Formation of a selenium-substituted rhodanese by reaction with selenite and glutathione: Possible role of a protein perselenide in a selenium delivery system. by Ogasawara Y, Lacourciere G, Stadtman TC.; 2001 Aug 14; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=55480
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Functional complementation of anthocyanin sequestration in the vacuole by widely divergent glutathione S-transferases. by Alfenito MR, Souer E, Goodman CD, Buell R, Mol J, Koes R, Walbot V.; 1998 Jul; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&rendertype=abstr act&artid=144053
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Functional Specific Binding of Testosterone to Schistosoma haematobium 28Kilodalton Glutathione S-Transferase. by Remoue F, Mani JC, Pugniere M, Schacht AM, Capron A, Riveau G.; 2002 Feb; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=127730
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Glutathione amide and its perthiol in anaerobic sulfur bacteria. by Bartsch RG, Newton GL, Sherrill C, Fahey RC.; 1996 Aug; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&rendertype=abstr act&artid=178251
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Glutathione and a UV Light --Induced Glutathione S-Transferase Are Involved in Signaling to Chalcone Synthase in Cell Cultures. by Loyall L, Uchida K, Braun S, Furuya M, Frohnmeyer H.; 2000 Oct; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=149131
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Glutathione and Homoglutathione Synthesis in Legume Root Nodules. by Matamoros MA, Moran JF, Iturbe-Ormaetxe I, Rubio MC, Becana M.; 1999 Nov 1; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=59450
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Glutathione and Homoglutathione Synthetases of Legume Nodules. Cloning, Expression, and Subcellular Localization. by Moran JF, Iturbe-Ormaetxe I, Matamoros MA, Rubio MC, Clemente MR, Brewin NJ, Becana M.; 2000 Nov 1; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=59235
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Glutathione biosynthesis in Arabidopsis trichome cells. by Gutierrez-Alcala G, Gotor C, Meyer AJ, Fricker M, Vega JM, Romero LC.; 2000 Sep 26; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=27156
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Glutathione Deficiency Decreases Tissue Ascorbate Levels in Newborn Rats: Ascorbate Spares Glutathione and Protects. by Mrtensson J, Meister A.; 1991 Jun 1; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&rendertype=abstr act&artid=51724
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Glutathione Deficiency Increases Hepatic Ascorbic Acid Synthesis in Adult Mice. by Martensson J, Meister A.; 1992 Dec 1; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&rendertype=abstr act&artid=50593
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Glutathione deficiency is associated with impaired survival in HIV disease. by Herzenberg LA, De Rosa SC, Dubs JG, Roederer M, Anderson MT, Ela SW, Deresinski SC, Herzenberg LA.; 1997 Mar 4; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=20026
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Glutathione Deficiency Leads to Mitochondrial Damage in Brain. by Jain A, Martensson J, Stole E, Auld PA, Meister A.; 1991 Mar 1; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&rendertype=abstr act&artid=51136
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Glutathione Derivatives Active against Trypanosoma brucei rhodesiense and T. brucei brucei In Vitro. by Daunes S, D'Silva C.; 2002 Feb; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=127061
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Glutathione Ester Delays the Onset of Scurvy in Ascorbate-Deficient Guinea Pigs. by Martensson J, Han J, Griffith OW, Meister A.; 1993 Jan 1; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&rendertype=abstr act&artid=45651
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Glutathione Is Involved in Environmental Stress Responses in Rhizobium tropici, Including Acid Tolerance. by Riccillo PM, Muglia CI, de Bruijn FJ, Roe AJ, Booth IR, Aguilar OM.; 2000 Mar 15; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=94474
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Glutathione is Required for Intestinal Function. by Martensson J, Jain A, Meister A.; 1990 Mar 1; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&rendertype=abstr act&artid=53553
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Glutathione is required for maximal transcription of the cobalamin biosynthetic and 1,2-propanediol utilization (cob/pdu) regulon and for the catabolism of ethanolamine, 1,2-propanediol, and propionate in Salmonella typhimurium LT2. by Rondon MR, Kazmierczak R, Escalante-Semerena JC.; 1995 Oct; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&rendertype=abstr act&artid=177348
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Glutathione levels in antigen-presenting cells modulate Th1 versus Th2 response patterns. by Peterson JD, Herzenberg LA, Vasquez K, Waltenbaugh C.; 1998 Mar 17; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=19696
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Glutathione metabolic genes coordinately respond to heavy metals and jasmonic acid in Arabidopsis. by Xiang C, Oliver DJ.; 1998 Sep; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&rendertype=abstr act&artid=144077
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Glutathione Regulates Activation-Dependent DNA Synthesis in Highly Purified Normal Human T Lymphocytes Stimulated via the CD2 and CD3 Antigens. by Suthanthiran M, Anderson ME, Sharma VK, Meister A.; 1990 May 1; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&rendertype=abstr act&artid=53896
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Glutathione S-Transferase Isoenzymes from Streptomyces griseus. by Dhar K, Dhar A, Rosazza JP.; 2003 Jan; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=152383
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Glutathione S-transferase M1 null genotype: lack of association with tumour characteristics and survival in advanced breast cancer. by Lizard-Nacol S, Coudert B, Colosetti P, Riedinger JM, Fargeot P, Brunet-Lecomte P.; 1999; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=13914
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Glutathione synthesis is essential for mouse development but not for cell growth in culture. by Shi ZZ, Osei-Frimpong J, Kala G, Kala SV, Barrios RJ, Habib GM, Lukin DJ, Danney CM, Matzuk MM, Lieberman MW.; 2000 May 9; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=25788
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Glutathione-Dependent Conversion of N-Ethylmaleimide to the Maleamic Acid by Escherichia coli: an Intracellular Detoxification Process. by McLaggan D, Rufino H, Jaspars M, Booth IR.; 2000 Apr; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=91998
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Glutathione-Induced Conversion of Pentavalent Antimony to Trivalent Antimony in Meglumine Antimoniate. by Frezard F, Demicheli C, Ferreira CS, Costa MA.; 2001 Mar; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=90392
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Glutathione-Mediated Destabilization in vitro of [2Fe-2S] Centers in the SoxR Regulatory Protein. by Ding H, Demple B.; 1996 Sep 3; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&rendertype=abstr act&artid=38448
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Glutathionylation of human thioredoxin: A possible crosstalk between the glutathione and thioredoxin systems. by Casagrande S, Bonetto V, Fratelli M, Gianazza E, Eberini I, Massignan T, Salmona M, Chang G, Holmgren A, Ghezzi P.; 2002 Jul 23; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=125000
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High Resistance to Cisplatin in Human Ovarian Cancer Cell Lines is Associated with Marked Increase of Glutathione Synthesis. by Godwin AK, Meister A, O'Dwyer PJ, Huang CS, Hamilton TC, Anderson ME.; 1992 Apr 1; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&rendertype=abstr act&artid=48805
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High-Affinity Transport of Glutathione is Part of a Multicomponent System Essential for Mitochondrial Function. by Martensson J, Lai JC, Meister A.; 1990 Sep 15; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&rendertype=abstr act&artid=54708
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Identification of an Ancillary Protein, YabF, Required for Activity of the KefC Glutathione-Gated Potassium Efflux System in Escherichia coli. by Miller S, Ness LS, Wood CM, Fox BC, Booth IR.; 2000 Nov 15; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=94807
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Identification of human prostaglandin E synthase: A microsomal, glutathionedependent, inducible enzyme, constituting a potential novel drug target. by Jakobsson PJ, Thoren S, Morgenstern R, Samuelsson B.; 1999 Jun 22; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=22058
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Immunogenicity of genetically engineered glutathione S-transferase fusion proteins containing a T-cell epitope from diphtheria toxin. by Pillai S, Dermody K, Metcalf B.; 1995 Apr; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&rendertype=abstr act&artid=173186
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Impairment of synaptic transmission by transient hypoxia in hippocampal slices: Improved recovery in glutathione peroxidase transgenic mice. by Furling D, Ghribi O, Lahsaini A, Mirault ME, Massicotte G.; 2000 Apr 11; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=18245
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Import and Metabolism of Glutathione by Streptococcus mutans. by Sherrill C, Fahey RC.; 1998 Mar 15; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=107044
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Importance of Glutathione for Growth and Survival of Escherichia coli Cells: Detoxification of Methylglyoxal and Maintenance of Intracellular K +. by Ferguson GP, Booth IR.; 1998 Aug 15; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=107434
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Increased resistance to acetaminophen hepatotoxicity in mice lacking glutathione Stransferase Pi. by Henderson CJ, Wolf CR, Kitteringham N, Powell H, Otto D, Park BK.; 2000 Nov 7; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=18834
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Increased skin tumorigenesis in mice lacking pi class glutathione S-transferases. by Henderson CJ, Smith AG, Ure J, Brown K, Bacon EJ, Wolf CR.; 1998 Apr 28; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=20251
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Increasing the Glutathione Content in a Chilling-Sensitive Maize Genotype Using Safeners Increased Protection against Chilling-Induced Injury. by Kocsy G, von Ballmoos P, Ruegsegger A, Szalai G, Galiba G, Brunold C.; 2001 Nov 1; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=129283
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Induction of Glutathione S-Transferases in Arabidopsis by Herbicide Safeners. by DeRidder BP, Dixon DP, Beussman DJ, Edwards R, Goldsbrough PB.; 2002 Nov 1; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=166668
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Infection with Salmonella typhimurium modulates the immune response to Schistosoma mansoni glutathione-S-transferase. by Comoy EE, Vendeville C, Capron A, Thyphronitis G.; 1997 Aug; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&rendertype=abstr act&artid=175461
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Inhibition of Glutathione Synthesis in the Newborn Rat: A Model for Endogenously Produced Oxidative Stress. by Martensson J, Jain A, Stole E, Frayer W, Auld PA, Meister A.; 1991 Oct 15; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&rendertype=abstr act&artid=52714
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Investigation of glutathione S-transferase zeta and the development of sporadic breast cancer. by Smith RA, Curran JE, Weinstein SR, Griffiths LR.; 2001; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=64834
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Isolation and Characterization of Glutathione S-Transferase Isozymes from Sorghum. by Gronwald JW, Plaisance KL.; 1998 Jul 1; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=34942
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Isolation and identification of a glutathione peroxidase homolog gene, gpxA, present in Neisseria meningitidis but absent in Neisseria gonorrhoeae. by Moore TD, Sparling PF.; 1995 Apr; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&rendertype=abstr act&artid=173197
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Lateral gene transfer and parallel evolution in the history of glutathione biosynthesis genes. by Copley SD, Dhillon JK.; 2002; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=115227
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Lethal and mutagenic actions of N-methyl-N'-nitro-N-nitrosoguanidine potentiated by oxidized glutathione, a seemingly harmless substance in the cellular environment. by Kumaresan KR, Springhorn SS, Lacks SA.; 1995 Jul; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&rendertype=abstr act&artid=177078
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Link between the Membrane-Bound Pyridine Nucleotide Transhydrogenase and Glutathione-Dependent Processes in Rhodobacter sphaeroides. by Hickman JW, Barber RD, Skaar EP, Donohue TJ.; 2002 Jan; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=139586
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Localization of [gamma]-Glutamylcysteine Synthetase and Glutathione Synthetase Activity in Maize Seedlings. by Ruegsegger A, Brunold C.; 1993 Feb; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&rendertype=abstr act&artid=160604
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Location of a Potential Transport Binding Site in a Sigma Class Glutathione Transferase by X-Ray Crystallography. by Ji X, Rosenvinge EC, Johnson WW, Armstrong RN, Gilliland GL.; 1996 Aug 6; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&rendertype=abstr act&artid=38648
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Maleylacetoacetate Isomerase (MAAI/GSTZ)-Deficient Mice Reveal a GlutathioneDependent Nonenzymatic Bypass in Tyrosine Catabolism. by Fernandez-Canon JM, Baetscher MW, Finegold M, Burlingame T, Gibson KM, Grompe M.; 2002 Jul; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=133921
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Manipulation of Glutathione and Amino Acid Biosynthesis in the Chloroplast. by Noctor G, Arisi AC, Jouanin L, Foyer CH.; 1998 Oct 1; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=34822
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Modification of Escherichia coli B glutathione synthetase with polyethylene glycol for clinical application to enzyme replacement therapy for glutathione deficiency. by Inoue Y, Sugiyama K, Ueminami H, Izawa S, Kimura A.; 1996 Nov; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&rendertype=abstr act&artid=170428
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Molecular modeling and in vitro activity of an HIV-1-encoded glutathione peroxidase. by Zhao L, Cox AG, Ruzicka JA, Bhat AA, Zhang W, Taylor EW.; 2000 Jun 6; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=18607
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Nitric Oxide Reacts with Intracellular Glutathione and Activates the Hexose Monophosphate Shunt in Human Neutrophils: Evidence for S-Nitrosoglutathione as a Bioactive Intermediary. by Clancy RM, Levartovsky D, Leszczynska-Piziak J, Yegudin J, Abramson SB.; 1994 Apr 26; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&rendertype=abstr act&artid=43645
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Nonsense-mediated Decay of mRNA for the Selenoprotein Phospholipid Hydroperoxide Glutathione Peroxidase Is Detectable in Cultured Cells but Masked or Inhibited in Rat Tissues. by Sun X, Li X, Moriarty PM, Henics T, LaDuca JP, Maquat LE.; 2001 Apr 1; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=32283
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Overexpression of cellular glutathione peroxidase rescues homocyst(e)ine-induced endothelial dysfunction. by Weiss N, Zhang YY, Heydrick S, Bierl C, Loscalzo J.; 2001 Oct 23; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=60083
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Overexpression of glutathione reductase but not glutathione synthetase leads to increases in antioxidant capacity and resistance to photoinhibition in poplar trees. by Foyer CH, Souriau N, Perret S, Lelandais M, Kunert KJ, Pruvost C, Jouanin L.; 1995 Nov; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&rendertype=abstr act&artid=161408
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Overexpression of Glutathione Synthetase in Indian Mustard Enhances Cadmium Accumulation and Tolerance. by Liang Zhu Y, Pilon-Smits EA, Jouanin L, Terry N.; 1999 Jan 1; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=32244
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Overexpression of the Gene Encoding the Multidrug Resistance-Associated Protein Results in Increased ATP-Dependent Glutathione S-Conjugate Transport. by Muller M, Meijer C, Zaman GJ, Borst P, Scheper RJ, Mulder NH, de Vries EG, Jansen PL.; 1994 Dec 20; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&rendertype=abstr act&artid=45575
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parB: An Auxin-Regulated Gene Encoding Glutathione S-Transferase. by Takahashi Y, Nagata T.; 1992 Jan 1; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&rendertype=abstr act&artid=48174
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Partial characterization of glutathione S-transferases from wheat (Triticum spp.) and purification of a safener-induced glutathione S-transferase from Triticum tauschii. by Riechers DE, Irzyk GP, Jones SS, Fuerst EP.; 1997 Aug; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&rendertype=abstr act&artid=158439
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Persistent inhibition of cell respiration by nitric oxide: Crucial role of S-nitrosylation of mitochondrial complex I and protective action of glutathione. by Clementi E, Brown GC, Feelisch M, Moncada S.; 1998 Jun 23; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=22706
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Photoaffinity Labeling of Arabidopsis thaliana Plasma Membrane Vesicles by 5Azido-[7-3H]Indole-3-Acetic Acid: Identification of a Glutathione S-Transferase. by Zettl R, Schell J, Palme K.; 1994 Jan 18; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&rendertype=abstr act&artid=43014
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Pink-eyed Dilution Protein Modulates Arsenic Sensitivity and Intracellular Glutathione Metabolism. by Staleva L, Manga P, Orlow SJ.; 2002 Dec 1; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=138627
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Polyclonal Antibodies to Glutathione S-Transferase- Verotoxin Subunit A Fusion Proteins Neutralize Verotoxins. by Leung PH, Peiris JS, Ng WW, Yam WC.; 2002 May; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=120006
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Polymorphism in glutathione S-transferase P1 is associated with susceptibility to chemotherapy-induced leukemia. by Allan JM, Wild CP, Rollinson S, Willett EV, Moorman AV, Dovey GJ, Roddam PL, Roman E, Cartwright RA, Morgan GJ.; 2001 Sep 25; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=58774
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Post-Transcriptional Regulation Prevents Accumulation of Glutathione Reductase Protein and Activity in the Bundle Sheath Cells of Maize. by Pastori GM, Mullineaux PM, Foyer CH.; 2000 Mar 1; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=58901
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Potential Role for Extracellular Glutathione-Dependent Ferric Reductase in Utilization of Environmental and Host Ferric Compounds by Histoplasma capsulatum. by Timmerman MM, Woods JP.; 2001 Dec; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=98861
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Purification and characterization of a glutathione S-transferase from benoxacortreated maize (Zea mays). by Irzyk GP, Fuerst EP.; 1993 Jul; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&rendertype=abstr act&artid=158850
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Purification and characterization of glutathione reductase isozymes specific for the state of cold hardiness of red spruce. by Hausladen A, Alscher RG.; 1994 May; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&rendertype=abstr act&artid=159347
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Purification of a Glutathione S-Transferase and a Glutathione Conjugate-Specific Dehydrogenase Involved in Isoprene Metabolism in Rhodococcus sp. Strain AD45. by van Hylckama Vlieg JE, Kingma J, Kruizinga W, Janssen DB.; 1999 Apr 1; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=93621
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Purification to Homogeneity and the N-Terminal Sequence of Human Leukotriene C4 Synthase: A Homodimeric Glutathione S-Transferase Composed of 18-kDa Subunits. by Nicholson DW, Ali A, Vaillancourt JP, Calaycay JR, Mumford RA, Zamboni RJ, FordHutchinson AW.; 1993 Mar 1; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&rendertype=abstr act&artid=46011
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Purified [gamma]-Glutamyl Transpeptidases from Tomato Exhibit High Affinity for Glutathione and Glutathione S-Conjugates. by Martin MN, Slovin JP.; 2000 Apr 1; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=58976
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Redesign of substrate-selectivity determining modules of glutathione transferase A1 -1 installs high catalytic efficiency with toxic alkenal products of lipid peroxidation. by Nilsson LO, Gustafsson A, Mannervik B.; 2000 Aug 15; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=16877
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Reduced Glutathione Is Required for Pertussis Toxin Secretion by Bordetella pertussis. by Stenson TH, Patton AK, Weiss AA.; 2003 Mar; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=148887
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Reengineering the glutathione S-transferase scaffold: A rational design strategy pays off. by Babbitt PC.; 2000 Sep 12; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=34038
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Relationship of Impairment of Schistosome 28-Kilodalton Glutathione S-Transferase (GST) Activity to Expression of Immunity to Schistosoma mattheei in Calves Vaccinated with Recombinant Schistosoma bovis 28-Kilodalton GST. by Grzych JM, De Bont J, Liu J, Neyrinck JL, Fontaine J, Vercruysse J, Capron A.; 1998 Mar; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=108027
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Role for Recombinant [gamma]-Glutamyltransferase from Treponema denticola in Glutathione Metabolism. by Chu L, Xu X, Dong Z, Cappelli D, Ebersole JL.; 2003 Jan; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=143415
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Role of Glutathione in an Animal Model of Myoglobinuric Acute Renal Failure. by Abul-Ezz SR, Walker PD, Shah SV.; 1991 Nov 1; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&rendertype=abstr act&artid=52815
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Role of Glutathione in Macrophage Control of Mycobacteria. by Venketaraman V, Dayaram YK, Amin AG, Ngo R, Green RM, Talaue MT, Mann J, Connell ND.; 2003 Apr; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=152031
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Role of Glutathione in the Export of Compounds from Cells by the MultidrugResistance-Associated Protein. by Zaman GJ, Lankelma J, van Tellingen O, Beijnen J, Dekker H, Paulusma C, Elferink RP, Baas F, Borst P.; 1995 Aug 15; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&rendertype=abstr act&artid=41211
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Role of Glutathione Metabolism of Treponema denticola in Bacterial Growth and Virulence Expression. by Chu L, Dong Z, Xu X, Cochran DL, Ebersole JL.; 2002 Mar; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=127775
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Role of the Ascorbate-Glutathione Cycle of Mitochondria and Peroxisomes in the Senescence of Pea Leaves. by Jimenez A, Hernandez JA, Pastori G, del Rio LA, Sevilla F.; 1998 Dec 1; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=34748
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Roles of the Enantioselective Glutathione S-Transferases in Cleavage of [beta]-Aryl Ether. by Masai E, Ichimura A, Sato Y, Miyauchi K, Katayama Y, Fukuda M.; 2003 Mar; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=150126
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Selenium Deficiency Reduces the Abundance of mRNA for Se-Dependent Glutathione Peroxidase 1 by a UGA-Dependent Mechanism Likely To Be Nonsense Codon-Mediated Decay of Cytoplasmic mRNA. by Moriarty PM, Reddy CC, Maquat LE.; 1998 May; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=110672
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Selenoprotein oxidoreductase with specificity for thioredoxin and glutathione systems. by Sun QA, Kirnarsky L, Sherman S, Gladyshev VN.; 2001 Mar 27; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=31110
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Soybean root nodule cDNA encoding glutathione reductase. by Tang X, Webb MA.; 1994 Mar; http://www.pubmedcentral.gov/picrender.fcgi?tool=pmcentrez&action=stream&blobt ype=pdf&artid=160711
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Structural Analysis and Antibody Response to the Extracellular Glutathione STransferases from Onchocerca volvulus. by Sommer A, Nimtz M, Conradt HS, Brattig N, Boettcher K, Fischer P, Walter RD, Liebau E.; 2001 Dec; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=98867
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Supercoiling affects the accessibility of glutathione to DNA-bound molecules: Positive supercoiling inhibits calicheamicin-induced DNA damage. by LaMarr WA, Yu L, Nicolaou KC, Dedon PC.; 1998 Jan 6; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=18140
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Suppression of Human Immunodeficiency Virus Expression in Chronically Infected Monocytic Cells by Glutathione, Glutathione Ester, and N-Acetylcysteine. by Kalebic T, Kinter A, Poli G, Anderson ME, Meister A, Fauci AS.; 1991 Feb 1; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&rendertype=abstr act&artid=50939
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Survival of Escherichia coli cells exposed to iodoacetate and chlorodinitrobenzene is independent of the glutathione-gated K+ efflux systems KefB and KefC. by Ness LS, Ferguson GP, Nikolaev Y, Booth IR.; 1997 Oct; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&rendertype=abstr act&artid=168720
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Synthesis of Glutathione in Leaves of Transgenic Poplar Overexpressing [gamma]Glutamylcysteine Synthetase. by Noctor G, Strohm M, Jouanin L, Kunert KJ, Foyer CH, Rennenberg H.; 1996 Nov; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&rendertype=abstr act&artid=158033
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Systemic and Mucosal Immune Responses after Intranasal Administration of Recombinant Mycobacterium bovis Bacillus Calmette-Guerin Expressing Glutathione S-Transferase from Schistosoma haematobium. by Kremer L, Dupre L, Riveau G, Capron A, Locht C.; 1998 Dec; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=108716
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Tandemly Duplicated Safener-Induced Glutathione S-Transferase Genes from Triticum tauschii Contribute to Genome- and Organ-Specific Expression in Hexaploid Wheat. by Xu F, Lagudah ES, Moose SP, Riechers DE.; 2002 Sep 1; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=166568
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Tetanus Toxin Fragment C Expressed in Live Salmonella Vaccines Enhances Antibody Responses to Its Fusion Partner Schistosoma haematobium Glutathione STransferase. by Lee JJ, Sinha KA, Harrison JA, de Hormaeche RD, Riveau G, Pierce RJ, Capron A, Wilson RA, Khan CM.; 2000 May; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=97452
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The Anopheles gambiae glutathione transferase supergene family: annotation, phylogeny and expression profiles. by Ding Y, Ortelli F, Rossiter LC, Hemingway J, Ranson H.; 2003; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=194574
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The Biological Functions of Glutathione Revisited in Arabidopsis Transgenic Plants with Altered Glutathione Levels. by Xiang C, Werner BL, Christensen E', Oliver DJ.; 2001 Jun 1; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=111149
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The chemistry of the S-nitrosoglutathione /glutathione system. by Singh SP, Wishnok JS, Keshive M, Deen WM, Tannenbaum SR.; 1996 Dec 10; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=26149
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The glutathione redox couple modulates zinc transfer from metallothionein to zincdepleted sorbitol dehydrogenase. by Jiang LJ, Maret W, Vallee BL.; 1998 Mar 31; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=19862
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The In Vivo Susceptibility of Leishmania donovani to Sodium Stibogluconate Is Drug Specific and Can Be Reversed by Inhibiting Glutathione Biosynthesis. by Carter KC, Sundar S, Spickett C, Pereira OC, Mullen AB.; 2003 May; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=153333
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The level of intracellular glutathione is a key regulator for the induction of stressactivated signal transduction pathways including Jun N-terminal protein kinases and p38 kinase by alkylating agents. by Wilhelm D, Bender K, Knebel A, Angel P.; 1997 Aug; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&rendertype=abstr act&artid=232331
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The mechanism of thioredoxin reductase from human placenta is similar to the mechanisms of lipoamide dehydrogenase and glutathione reductase and is distinct from the mechanism of thioredoxin reductase from Escherichia coli. by Arscott LD, Gromer S, Schirmer RH, Becker K, Williams CH Jr.; 1997 Apr 15; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=20490
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The role of alternative mRNA splicing in generating heterogeneity within the Anopheles gambiae class I glutathione S-transferase family. by Ranson H, Collins F, Hemingway J.; 1998 Nov 24; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=24365
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The ROOT MERISTEMLESS1/CADMIUM SENSITIVE2 Gene Defines a Glutathione-Dependent Pathway Involved in Initiation and Maintenance of Cell Division during Postembryonic Root Development. by Vernoux T, Wilson RC, Seeley KA, Reichheld JP, Muroy S, Brown S, Maughan SC, Cobbett CS, Van Montagu M, Inze D, May MJ, Sung ZR.; 2000 Jan; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=140217
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Thermosensitive Phenotype of Transgenic Mice Overproducing Human Glutathione Peroxidases. by Mirochnitchenko O, Palnitkar U, Philbert M, Inouye M.; 1995 Aug 29; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&rendertype=abstr act&artid=41107
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Thiram and dimethyldithiocarbamic acid interconversion in Saccharomyces cerevisiae: a possible metabolic pathway under the control of the glutathione redox cycle. by Elskens MT, Penninckx MJ.; 1997 Jul; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&rendertype=abstr act&artid=168582
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Trans-Activation of Glutathione Transferase P Gene During Chemical Hepatocarcinogenesis of the Rat. by Morimura S, Suzuki T, Hochi S, Yuki A, Nomura K, Kitagawa T, Nagatsu I, Imagawa M, Muramatsu M.; 1993 Mar 1; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&rendertype=abstr act&artid=46021
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Transport of Glutathione Diethyl Ester Into Human Cells. by Levy EJ, Anderson ME, Meister A.; 1993 Oct 1; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&rendertype=abstr act&artid=47524
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Two Adjacent AP-1-Like Binding Sites Form the Electrophile-Responsive Element of the Murine Glutathione S-Transferase Ya Subunit Gene. by Friling RS, Bergelson S, Daniel V.; 1992 Jan 15; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&rendertype=abstr act&artid=48300
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Xenobiotic-Inducible Expression of Murine Glutathione S-Transferase Ya Subunit Gene is Controlled by an Electrophile-Responsive Element. by Friling RS, Bensimon A, Tichauer Y, Daniel V.; 1990 Aug 15; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&rendertype=abstr act&artid=54512
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 glutathione, simply go to the PubMed Web site at http://www.ncbi.nlm.nih.gov/pubmed. Type “glutathione” (or synonyms) into the search box, and click “Go.” The following is the type of output you can expect from PubMed for glutathione (hyperlinks lead to article summaries): •
3'UTRs of glutathione peroxidases differentially affect selenium-dependent mRNA stability and selenocysteine incorporation efficiency. Author(s): Muller C, Wingler K, Brigelius-Flohe R. Source: Biological Chemistry. 2003 January; 384(1): 11-8. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12674495&dopt=Abstract
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A cellular model for Friedreich Ataxia reveals small-molecule glutathione peroxidase mimetics as novel treatment strategy. Author(s): Jauslin ML, Wirth T, Meier T, Schoumacher F. Source: Human Molecular Genetics. 2002 November 15; 11(24): 3055-63. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12417527&dopt=Abstract
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A novel amphibian Pi-class glutathione transferase isoenzyme from Xenopus laevis: importance of phenylalanine 111 in the H-site. Author(s): De Luca A, Favaloro B, Carletti E, Sacchetta P, Di Ilio C. Source: The Biochemical Journal. 2003 July 15; 373(Pt 2): 539-45. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12710888&dopt=Abstract
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PubMed was developed by the National Center for Biotechnology Information (NCBI) at the National Library of Medicine (NLM) at the National Institutes of Health (NIH). The PubMed database was developed in conjunction with publishers of biomedical literature as a search tool for accessing literature citations and linking to full-text journal articles at Web sites of participating publishers. Publishers that participate in PubMed supply NLM with their citations electronically prior to or at the time of publication.
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A novel missense mutation in the gamma-glutamylcysteine synthetase catalytic subunit gene causes both decreased enzymatic activity and glutathione production. Author(s): Hamilton D, Wu JH, Alaoui-Jamali M, Batist G. Source: Blood. 2003 July 15; 102(2): 725-30. Epub 2003 March 27. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12663448&dopt=Abstract
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A population-based study of glutathione S-transferase M1, T1 and P1 genotypes and risk for lung cancer. Author(s): Nazar-Stewart V, Vaughan TL, Stapleton P, Van Loo J, Nicol-Blades B, Eaton DL. Source: Lung Cancer (Amsterdam, Netherlands). 2003 June; 40(3): 247-58. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12781423&dopt=Abstract
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Acetaldehyde impairs mitochondrial glutathione transport in HepG2 cells through endoplasmic reticulum stress. Author(s): Lluis JM, Colell A, Garcia-Ruiz C, Kaplowitz N, Fernandez-Checa JC. Source: Gastroenterology. 2003 March; 124(3): 708-24. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12612910&dopt=Abstract
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Activity of glutathione-metabolizing and antioxidant enzymes in malignant and benign tumors of human lungs. Author(s): Korotkina RN, Matskevich GN, Devlikanova ASh, Vishnevskii AA, Kunitsyn AG, Karelin AA. Source: Bulletin of Experimental Biology and Medicine. 2002 June; 133(6): 606-8. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12447480&dopt=Abstract
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Aldehydes and glutathione in exhaled breath condensate of children with asthma exacerbation. Author(s): Corradi M, Folesani G, Andreoli R, Manini P, Bodini A, Piacentini G, Carraro S, Zanconato S, Baraldi E. Source: American Journal of Respiratory and Critical Care Medicine. 2003 February 1; 167(3): 395-9. Epub 2002 October 31. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12411284&dopt=Abstract
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Allele frequencies for glutathione S-transferase and N-acetyltransferase 2 differ in African population groups and may be associated with oesophageal cancer or tuberculosis incidence. Author(s): Adams CH, Werely CJ, Victor TC, Hoal EG, Rossouw G, van Helden PD. Source: Clinical Chemistry and Laboratory Medicine : Cclm / Fescc. 2003 April; 41(4): 600-5. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12747608&dopt=Abstract
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Allelic variants of the human glutathione S-transferase P1 gene confer differential cytoprotection against anticancer agents in Escherichia coli. Author(s): Ishimoto TM, Ali-Osman F. Source: Pharmacogenetics. 2002 October; 12(7): 543-53. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12360105&dopt=Abstract
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Alteration of glutathione S-transferase levels in Barrett's metaplasia compared to normal oesophageal epithelium. Author(s): Cobbe SC, Scobie GC, Pohler E, Hayes JD, Kernohan NM, Dillon JF. Source: European Journal of Gastroenterology & Hepatology. 2003 January; 15(1): 41-7. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12544693&dopt=Abstract
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Alterations in m-RNA expression for Cu,Zn-superoxide dismutase and glutathione peroxidase in the basal ganglia of MPTP-treated marmosets and patients with Parkinson's disease. Author(s): Kunikowska G, Jenner P. Source: Brain Research. 2003 April 11; 968(2): 206-18. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12663090&dopt=Abstract
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Alternative mRNAs arising from trans-splicing code for mitochondrial and cytosolic variants of Echinococcus granulosus thioredoxin Glutathione reductase. Author(s): Agorio A, Chalar C, Cardozo S, Salinas G. Source: The Journal of Biological Chemistry. 2003 April 11; 278(15): 12920-8. Epub 2003 January 21. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12538593&dopt=Abstract
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Analysis of the Glutathione S-transferase M1 gene using pyrosequencing and multiplex PCR--no evidence of association to glaucoma. Author(s): Jansson M, Rada A, Tomic L, Larsson LI, Wadelius C. Source: Experimental Eye Research. 2003 August; 77(2): 239-43. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12873455&dopt=Abstract
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Antibodies against glutathione S-transferase T1 in patients with immune hepatitis after liver transplantation. Author(s): Aguilera I, Wichmann I, Sousa JM, Bernardos A, Franco E, Garcia-Lozano R, Gonzalez-Escribano MF, Nunez-Roldan A. Source: Transplantation Proceedings. 2003 March; 35(2): 712. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12644106&dopt=Abstract
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Antimelanogenic activity of hydrocoumarins in cultured normal human melanocytes by stimulating intracellular glutathione synthesis. Author(s): Yamamura T, Onishi J, Nishiyama T. Source: Archives of Dermatological Research. 2002 November; 294(8): 349-54. Epub 2002 September 28. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12420103&dopt=Abstract
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Aplidin induces apoptosis in human cancer cells via glutathione depletion and sustained activation of the epidermal growth factor receptor, Src, JNK, and p38 MAPK. Author(s): Cuadrado A, Garcia-Fernandez LF, Gonzalez L, Suarez Y, Losada A, Alcaide V, Martinez T, Fernandez-Sousa JM, Sanchez-Puelles JM, Munoz A. Source: The Journal of Biological Chemistry. 2003 January 3; 278(1): 241-50. Epub 2002 October 31. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12414812&dopt=Abstract
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Are kavalactones the hepatotoxic principle of kava extracts? The pitfalls of the glutathione theory. Author(s): Schmidt M. Source: Journal of Alternative and Complementary Medicine (New York, N.Y.). 2003 April; 9(2): 183-7; Author Reply 187-8. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12804070&dopt=Abstract
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Arsenic trioxide induces apoptosis in cells of MOLT-4 and its daunorubicin-resistant cell line via depletion of intracellular glutathione, disruption of mitochondrial membrane potential and activation of caspase-3. Author(s): Hu XM, Hirano T, Oka K. Source: Cancer Chemotherapy and Pharmacology. 2003 July; 52(1): 47-58. Epub 2003 May 16. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12750841&dopt=Abstract
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Association between a glutathione S-transferase A1 promoter polymorphism and survival after breast cancer treatment. Author(s): Sweeney C, Ambrosone CB, Joseph L, Stone A, Hutchins LF, Kadlubar FF, Coles BF. Source: International Journal of Cancer. Journal International Du Cancer. 2003 March 1; 103(6): 810-4. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12516103&dopt=Abstract
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Association between glutathione S-transferase p1 polymorphisms and lung cancer risk in Caucasians: a case-control study. Author(s): Wang Y, Spitz MR, Schabath MB, Ali-Osman F, Mata H, Wu X. Source: Lung Cancer (Amsterdam, Netherlands). 2003 April; 40(1): 25-32. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12660004&dopt=Abstract
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Association between the risk of coronary artery disease in South Asians and a deletion polymorphism in glutathione S-transferase M1. Author(s): Wilson MH, Grant PJ, Kain K, Warner DP, Wild CP. Source: Biomarkers : Biochemical Indicators of Exposure, Response, and Susceptibility to Chemicals. 2003 January-February; 8(1): 43-50. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12519635&dopt=Abstract
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Association of common variation in glutathione S-transferase genes with premature development of cardiovascular disease in patients with systemic sclerosis. Author(s): Palmer CN, Young V, Ho M, Doney A, Belch JJ. Source: Arthritis and Rheumatism. 2003 March; 48(3): 854-5. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12632442&dopt=Abstract
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Association of genetic polymorphisms of glutathione-S-transferase genes (GSTM1, GSTT1 and GSTP1) with familial prostate cancer risk in a Japanese population. Author(s): Nakazato H, Suzuki K, Matsui H, Koike H, Okugi H, Ohtake N, Takei T, Nakata S, Hasumi M, Ito K, Kurokawa K, Yamanaka H. Source: Anticancer Res. 2003 May-June; 23(3C): 2897-902. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12926131&dopt=Abstract
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Association study between glutathione S-transferase P1 polymorphism and schizophrenia in the Korean population. Author(s): Pae CU, Kim JJ, Lee SJ, Lee CU, Lee C, Paik IH, Park HR, Yang S, Serretti A. Source: Progress in Neuro-Psychopharmacology & Biological Psychiatry. 2003 May; 27(3): 519-23. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12691788&dopt=Abstract
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Associations between carcinogen-DNA damage, glutathione S-transferase genotypes, and risk of lung cancer in the prospective Physicians' Health Cohort Study. Author(s): Perera FP, Mooney LA, Stampfer M, Phillips DH, Bell DA, Rundle A, Cho S, Tsai WY, Ma J, Blackwood A, Tang D; Physicians' Health Cohort Study. Source: Carcinogenesis. 2002 October; 23(10): 1641-6. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12376472&dopt=Abstract
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Basal expression of the human MAPEG members microsomal glutathione transferase 1 and prostaglandin E synthase genes is mediated by Sp1 and Sp3. Author(s): Ekstrom L, Lyrenas L, Jakobsson PJ, Morgenstern R, Kelner MJ. Source: Biochimica Et Biophysica Acta. 2003 June 19; 1627(2-3): 79-84. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12818425&dopt=Abstract
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Bioflavonoid stimulation of glutathione transport by the 190-kDa multidrug resistance protein 1 (MRP1). Author(s): Leslie EM, Deeley RG, Cole SP. Source: Drug Metabolism and Disposition: the Biological Fate of Chemicals. 2003 January; 31(1): 11-5. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12485947&dopt=Abstract
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Biosynthesis of toxic glutathione conjugates from halogenated alkenes. Author(s): Dekant W. Source: Toxicology Letters. 2003 September 15; 144(1): 49-54. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12919723&dopt=Abstract
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Blood glutathione as a surrogate marker of cancer tissue glutathione S-transferase activity in non-small cell lung cancer and squamous cell carcinoma of the head and neck. Author(s): Ferruzzi E, Franceschini R, Cazzolato G, Geroni C, Fowst C, Pastorino U, Tradati N, Tursi J, Dittadi R, Gion M. Source: European Journal of Cancer (Oxford, England : 1990). 2003 May; 39(7): 1019-29. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12706373&dopt=Abstract
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Brugia malayi and Wuchereria bancrofti: gene comparison and recombinant expression of pi-class related glutathione S-transferases. Author(s): Rathaur S, Fischer P, Domagalski M, Walter RD, Liebau E. Source: Experimental Parasitology. 2003 March-April; 103(3-4): 177-81. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12880597&dopt=Abstract
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Carbamazepine-provoked hepatotoxicity and possible aetiopathological role of glutathione in the events. Retrospective review of old data and call for new investigation. Author(s): Kalapos MP. Source: Adverse Drug Reactions and Toxicological Reviews. 2002; 21(3): 123-41. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12298421&dopt=Abstract
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cGMP and glutathione-conjugate transport in human erythrocytes. Author(s): Klokouzas A, Wu CP, van Veen HW, Barrand MA, Hladky SB. Source: European Journal of Biochemistry / Febs. 2003 September; 270(18): 3696-708. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12950253&dopt=Abstract
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Characterization of microsomal, glutathione dependent prostaglandin E synthase. Author(s): Jakobsson PJ, Thoren S, Morgenstern R, Samuelsson B. Source: Advances in Experimental Medicine and Biology. 2002; 507: 287-91. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12664599&dopt=Abstract
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Characterization of the human Omega class glutathione transferase genes and associated polymorphisms. Author(s): Whitbread AK, Tetlow N, Eyre HJ, Sutherland GR, Board PG. Source: Pharmacogenetics. 2003 March; 13(3): 131-44. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12618591&dopt=Abstract
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Chloroform, carbon tetrachloride and glutathione depletion induce secondary genotoxicity in liver cells via oxidative stress. Author(s): Beddowes EJ, Faux SP, Chipman JK. Source: Toxicology. 2003 May 3; 187(2-3): 101-15. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12699900&dopt=Abstract
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Chronic arsenic-exposed human prostate epithelial cells exhibit stable arsenic tolerance: mechanistic implications of altered cellular glutathione and glutathione Stransferase. Author(s): Brambila EM, Achanzar WE, Qu W, Webber MM, Waalkes MP. Source: Toxicology and Applied Pharmacology. 2002 September 1; 183(2): 99-107. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12387749&dopt=Abstract
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Citicoline increases glutathione redox ratio and reduces caspase-3 activation and cell death in staurosporine-treated SH-SY5Y human neuroblastoma cells. Author(s): Barrachina M, Secades J, Lozano R, Gomez-Santos C, Ambrosio S, Ferrer I. Source: Brain Research. 2002 December 6; 957(1): 84-90. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12443983&dopt=Abstract
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c-Jun N-terminal kinase negatively regulates lipopolysaccharide-induced IL-12 production in human macrophages: role of mitogen-activated protein kinase in glutathione redox regulation of IL-12 production. Author(s): Utsugi M, Dobashi K, Ishizuka T, Endou K, Hamuro J, Murata Y, Nakazawa T, Mori M. Source: Journal of Immunology (Baltimore, Md. : 1950). 2003 July 15; 171(2): 628-35. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12847227&dopt=Abstract
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Clarification of the role of key active site residues of glutathione transferase zeta/maleylacetoacetate isomerase by a new spectrophotometric technique. Author(s): Board PG, Taylor MC, Coggan M, Parker MW, Lantum HB, Anders MW. Source: The Biochemical Journal. 2003 September 15; 374(Pt 3): 731-7. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12852784&dopt=Abstract
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Clonorchis sinensis: glutathione S-transferase as a serodiagnostic antigen for detecting IgG and IgE antibodies. Author(s): Hong SJ, Yun Kim T, Gan XX, Shen LY, Sukontason K, Sukontason K, Kang SY. Source: Experimental Parasitology. 2002 August; 101(4): 231-3. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12594964&dopt=Abstract
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Comparison of activities dependent on glutathione S-transferase and cytochrome P450 IA1 in cultured keratinocytes and reconstructed epidermal models. Author(s): Harris IR, Siefken W, Beck-Oldach K, Brandt M, Wittern KP, Pollet D. Source: Skin Pharmacology and Applied Skin Physiology. 2002; 15 Suppl 1: 59-67. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12476009&dopt=Abstract
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Contribution of glycine 146 to a conserved folding module affecting stability and refolding of human glutathione transferase p1-1. Author(s): Kong GK, Polekhina G, McKinstry WJ, Parker MW, Dragani B, Aceto A, Paludi D, Principe DR, Mannervik B, Stenberg G. Source: The Journal of Biological Chemistry. 2003 January 10; 278(2): 1291-302. Epub 2002 October 31. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12414796&dopt=Abstract
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Coordinate regulation of glutathione biosynthesis and release by Nrf2-expressing glia potently protects neurons from oxidative stress. Author(s): Shih AY, Johnson DA, Wong G, Kraft AD, Jiang L, Erb H, Johnson JA, Murphy TH. Source: The Journal of Neuroscience : the Official Journal of the Society for Neuroscience. 2003 April 15; 23(8): 3394-406. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12716947&dopt=Abstract
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Cotransport of reduced glutathione with bile salts by MRP4 (ABCC4) localized to the basolateral hepatocyte membrane. Author(s): Rius M, Nies AT, Hummel-Eisenbeiss J, Jedlitschky G, Keppler D. Source: Hepatology (Baltimore, Md.). 2003 August; 38(2): 374-84. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12883481&dopt=Abstract
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Coupling between cyclooxygenases and prostaglandin F(2alpha) synthase. Detection of an inducible, glutathione-activated, membrane-bound prostaglandin F(2alpha)synthetic activity. Author(s): Nakashima K, Ueno N, Kamei D, Tanioka T, Nakatani Y, Murakami M, Kudo I. Source: Biochimica Et Biophysica Acta. 2003 July 21; 1633(2): 96-105. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12880869&dopt=Abstract
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Covalent binding to glutathione of the DNA-alkylating antitumor agent, S23906-1. Author(s): David-Cordonnier MH, Laine W, Joubert A, Tardy C, Goossens JF, Kouach M, Briand G, Thi Mai HD, Michel S, Tillequin F, Koch M, Leonce S, Pierre A, Bailly C. Source: European Journal of Biochemistry / Febs. 2003 July; 270(13): 2848-59. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12823555&dopt=Abstract
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Covalent coupling of reduced glutathione with ribose: loss of cosubstrate ability to glutathione peroxidase. Author(s): Januel C, Fay LB, Ruggiero D, Lagarde M, Vericel E. Source: Biochimica Et Biophysica Acta. 2003 March 17; 1620(1-3): 125-32. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12595081&dopt=Abstract
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Crystal structure of the 28 kDa glutathione S-transferase from Schistosoma haematobium. Author(s): Johnson KA, Angelucci F, Bellelli A, Herve M, Fontaine J, Tsernoglou D, Capron A, Trottein F, Brunori M. Source: Biochemistry. 2003 September 2; 42(34): 10084-94. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12939136&dopt=Abstract
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Depletion of phospholipid hydroperoxide glutathione peroxidase up-regulates arachidonate metabolism by 12S-lipoxygenase and cyclooxygenase 1 in human epidermoid carcinoma A431 cells. Author(s): Chen CJ, Huang HS, Chang WC. Source: The Faseb Journal : Official Publication of the Federation of American Societies for Experimental Biology. 2003 September; 17(12): 1694-6. Epub 2003 July 03. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12958179&dopt=Abstract
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Design of a monomeric human glutathione transferase GSTP1, a structurally stable but catalytically inactive protein. Author(s): Abdalla AM, Bruns CM, Tainer JA, Mannervik B, Stenberg G. Source: Protein Engineering. 2002 October; 15(10): 827-34. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12468717&dopt=Abstract
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Detection of elevated glutathione in meningiomas by quantitative in vivo 1H MRS. Author(s): Opstad KS, Provencher SW, Bell BA, Griffiths JR, Howe FA. Source: Magnetic Resonance in Medicine : Official Journal of the Society of Magnetic Resonance in Medicine / Society of Magnetic Resonance in Medicine. 2003 April; 49(4): 632-7. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12652533&dopt=Abstract
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Determination of nitric oxide-induced effects on tissue levels of glutathione and mitochondrial membrane potential. Author(s): Wright TL, Li CQ, Trudel LJ, Wogan GN, Tannenbaum SR. Source: Methods Enzymol. 2002; 359: 319-28. No Abstract Available. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12481583&dopt=Abstract
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Diazenecarboxamide UP-91, a potential anticancer agent, acts by reducing cellular glutathione content. Author(s): Moskatelo D, Polanc S, Kosmrlj J, Vukovic L, Osmak M. Source: Pharmacology & Toxicology. 2002 November; 91(5): 258-63. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12570033&dopt=Abstract
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Dietary isothiocyanates, glutathione S-transferase polymorphisms and colorectal cancer risk in the Singapore Chinese Health Study. Author(s): Seow A, Yuan JM, Sun CL, Van Den Berg D, Lee HP, Yu MC. Source: Carcinogenesis. 2002 December; 23(12): 2055-61. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12507929&dopt=Abstract
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Disturbed glutathione metabolism and decreased antioxidant levels in human immunodeficiency virus-infected patients during highly active antiretroviral therapy-potential immunomodulatory effects of antioxidants. Author(s): Aukrust P, Muller F, Svardal AM, Ueland T, Berge RK, Froland SS. Source: The Journal of Infectious Diseases. 2003 July 15; 188(2): 232-8. Epub 2003 June 09. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12854078&dopt=Abstract
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Down-regulation of alpha class glutathione S-transferase by interleukin-1beta in human intestinal epithelial cells (Caco-2) in culture. Author(s): Romero L, Higgins MA, Gilmore J, Boudreau K, Maslen A, Barker HJ, Kirby GM. Source: Drug Metabolism and Disposition: the Biological Fate of Chemicals. 2002 November; 30(11): 1186-93. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12386123&dopt=Abstract
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Dual role of glutathione in modulating camptothecin activity: depletion potentiates activity, but conjugation enhances the stability of the topoisomerase I-DNA cleavage complex. Author(s): Gamcsik MP, Kasibhatla MS, Adams DJ, Flowers JL, Colvin OM, Manikumar G, Wani M, Wall ME, Kohlhagen G, Pommier Y. Source: Molecular Cancer Therapeutics. 2001 November; 1(1): 11-20. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12467234&dopt=Abstract
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Effect of epoxide hydrolase and glutathione S-tranferase genotypes on the induction of micronuclei and DNA damage by styrene-7,8-oxide in vitro. Author(s): Laffon B, Perez-Cadahia B, Pasaro E, Mendez J. Source: Mutation Research. 2003 April 20; 536(1-2): 49-59. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12694745&dopt=Abstract
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Effect of oxidative stress on glutathione pathway in red blood cells from patients with insulin-dependent diabetes mellitus. Author(s): Dincer Y, Akcay T, Alademir Z, Ilkova H. Source: Metabolism: Clinical and Experimental. 2002 October; 51(10): 1360-2. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12370859&dopt=Abstract
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Effect of S-(1,2-dicarboxyethyl) glutathione and S-(1,2-dicarboxyethyl) cysteine on the stimulus-induced superoxide generation and tyrosyl phosphorylation of proteins in human neutrophils. Author(s): Wang C, Lu H, Chen G, Yamashita K, Manabe M, Kodama H. Source: Clinical Chemistry and Laboratory Medicine : Cclm / Fescc. 2002 November; 40(11): 1101-4. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12521225&dopt=Abstract
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Effect of TEGDMA on the intracellular glutathione concentration of human gingival fibroblasts. Author(s): Engelmann J, Leyhausen G, Leibfritz D, Geurtsen W. Source: Journal of Biomedical Materials Research. 2002; 63(6): 746-51. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12418019&dopt=Abstract
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Effect of vitamin C supplementation on reduced glutathione and malondialdehyde in patients with acute myocardial infarction. Author(s): Miglani A, Seth RK, Siwach SB. Source: Clinica Chimica Acta; International Journal of Clinical Chemistry. 2003 January; 327(1-2): 187-8. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12482635&dopt=Abstract
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Effect of whey protein isolate on intracellular glutathione and oxidant-induced cell death in human prostate epithelial cells. Author(s): Kent KD, Harper WJ, Bomser JA. Source: Toxicology in Vitro : an International Journal Published in Association with Bibra. 2003 February; 17(1): 27-33. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12537959&dopt=Abstract
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Effects of a vitamin E-bonded membrane and of glutathione on anemia and erythropoietin requirements in hemodialysis patients. Author(s): Usberti M, Gerardi G, Micheli A, Tira P, Bufano G, Gaggia P, Movilli E, Cancarini GC, De Marinis S, D'Avolio G, Broccoli R, Manganoni A, Albertin A, Di Lorenzo D. Source: Journal of Nephrology. 2002 September-October; 15(5): 558-64. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12455724&dopt=Abstract
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Effects of chronic hepatic dysfunction on pulmonary glutathione homeostasis. Author(s): Foreman MG, Hoor TT, Brown LA, Moss M. Source: Alcoholism, Clinical and Experimental Research. 2002 December; 26(12): 1840-5. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12500108&dopt=Abstract
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Efficacy of a glutathione S-transferase pi-activated prodrug in platinum-resistant ovarian cancer cells. Author(s): Townsend DM, Shen H, Staros AL, Gate L, Tew KD. Source: Molecular Cancer Therapeutics. 2002 October; 1(12): 1089-95. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12481432&dopt=Abstract
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Engineering a new C-terminal tail in the H-site of human glutathione transferase P11: structural and functional consequences. Author(s): Micaloni C, Kong GK, Mazzetti AP, Nuccetelli M, Antonini G, Stella L, McKinstry WJ, Polekhina G, Rossjohn J, Federici G, Ricci G, Parker MW, Lo Bello M. Source: Journal of Molecular Biology. 2003 January 3; 325(1): 111-22. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12473455&dopt=Abstract
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Enhanced lipid peroxidation in epileptics with null genotype of glutathione Stransferase M1 and intractable seizure. Author(s): Liu CS, Tsai CS. Source: Japanese Journal of Pharmacology. 2002 November; 90(3): 291-4. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12499585&dopt=Abstract
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Enhancement of diethylstilbestrol induced cytotoxicity by bcl-2 antisense oligodeoxynucleotides and a glutathione depletor for prostate cancer. Author(s): Kikuchi E, Nakashima J, Horiguchi Y, Oya M, Ohigashi T, Murai M. Source: The Journal of Urology. 2003 February; 169(2): 730-4. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12544353&dopt=Abstract
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Enhancement of the depigmenting effect of hydroquinone and 4-hydroxyanisole by all-trans-retinoic acid (tretinoin): the impairment of glutathione-dependent cytoprotection? Author(s): Kasraee B, Handjani F, Aslani FS. Source: Dermatology (Basel, Switzerland). 2003; 206(4): 289-91. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12771467&dopt=Abstract
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Epidermal growth factor receptor is a common mediator of quinone-induced signaling leading to phosphorylation of connexin-43: role of glutathione and tyrosine phosphatases. Author(s): Abdelmohsen K, Gerber PA, von Montfort C, Sies H, Klotz LO. Source: The Journal of Biological Chemistry. 2003 October 3; 278(40): 38360-7. Epub 2003 July 21. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12874275&dopt=Abstract
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Erythrocyte superoxide dismutase, glutathione peroxidase and catalase activities in healthy male subjects in Republic of Macedonia. Author(s): Bogdanska JJ, Korneti P, Todorova B. Source: Bratisl Lek Listy. 2003; 104(3): 108-14. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12940695&dopt=Abstract
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Estrogenic effects of phenolic compounds on glucose-6-phosphate dehydrogenase in MCF-7 cells and uterine glutathione peroxidase in rats. Author(s): Kim KB, Seo KW, Kim YJ, Park M, Park CW, Kim PY, Kim JI, Lee SH. Source: Chemosphere. 2003 March; 50(9): 1167-73. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12547330&dopt=Abstract
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Ethnic diversity in a critical gene responsible for glutathione synthesis. Author(s): Willis AS, Freeman ML, Summar SR, Barr FE, Williams SM, Dawson E, Summar ML. Source: Free Radical Biology & Medicine. 2003 January 1; 34(1): 72-6. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12498981&dopt=Abstract
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Evaluation of the microsomal glutathione S-transferase 3 (MGST3) locus on 1q23 as a Type 2 diabetes susceptibility gene in Pima Indians. Author(s): Thameem F, Yang X, Permana PA, Wolford JK, Bogardus C, Prochazka M. Source: Human Genetics. 2003 September; 113(4): 353-8. Epub 2003 July 26. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12898215&dopt=Abstract
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Exploration of in vitro pro-drug activation and futile cycling by glutathione Stransferases: thiol ester hydrolysis and inhibitor maturation. Author(s): Ibarra C, Grillo MP, Lo Bello M, Nucettelli M, Bammler TK, Atkins WM. Source: Archives of Biochemistry and Biophysics. 2003 June 15; 414(2): 303-11. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12781783&dopt=Abstract
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Exposure levels and cytochrome P450 1A2 activity, but not N-acetyltransferase, glutathione S-transferase (GST) M1 and T1, influence urinary mutagen excretion in smokers. Author(s): Pavanello S, Simioli P, Lupi S, Gregorio P, Clonfero E. Source: Cancer Epidemiology, Biomarkers & Prevention : a Publication of the American Association for Cancer Research, Cosponsored by the American Society of Preventive Oncology. 2002 October; 11(10 Pt 1): 998-1003. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12376499&dopt=Abstract
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Expression and regulation of glutathione S-transferase P1-1 in cultured human epidermal cells. Author(s): Zhang Y, Gonzalez V, Xu MJ. Source: Journal of Dermatological Science. 2002 December; 30(3): 205-14. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12443843&dopt=Abstract
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Feasibility and correlates of arsenic trioxide combined with ascorbic acid-mediated depletion of intracellular glutathione for the treatment of relapsed/refractory multiple myeloma. Author(s): Bahlis NJ, McCafferty-Grad J, Jordan-McMurry I, Neil J, Reis I, KharfanDabaja M, Eckman J, Goodman M, Fernandez HF, Boise LH, Lee KP. Source: Clinical Cancer Research : an Official Journal of the American Association for Cancer Research. 2002 December; 8(12): 3658-68. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12473574&dopt=Abstract
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Functional characterization of cis- and trans-regulatory elements involved in expression of phospholipid hydroperoxide glutathione peroxidase. Author(s): Ufer C, Borchert A, Kuhn H. Source: Nucleic Acids Research. 2003 August 1; 31(15): 4293-303. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12888488&dopt=Abstract
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Functional relationship of alpha-glutathione S-transferase and glutathione Stransferase activity in machine-preserved non-heart-beating donor kidneys. Author(s): Van Kreel BK, Janssen MA, Kootstra G. Source: Transplant International : Official Journal of the European Society for Organ Transplantation. 2002 November; 15(11): 546-9. Epub 2002 October 03. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12461658&dopt=Abstract
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Gender-related differences in erythrocyte glutathione peroxidase activity in healthy subjects. Author(s): Massafra C, Gioia D, De Felice C, Muscettola M, Longini M, Buonocore G. Source: Clinical Endocrinology. 2002 November; 57(5): 663-7. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12390342&dopt=Abstract
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Genetic polymorphism of cytochrome P450 1A1 (Cyp1A1) and glutathione transferases (M1, T1 and P1) among Africans. Author(s): Dandara C, Sayi J, Masimirembwa CM, Magimba A, Kaaya S, De Sommers K, Snyman JR, Hasler JA. Source: Clinical Chemistry and Laboratory Medicine : Cclm / Fescc. 2002 September; 40(9): 952-7. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12435115&dopt=Abstract
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Genetic polymorphism of N-acetyltransferase and glutathione S-transferase related to neoplasm of genitourinary system. Minireview. Author(s): Reszka E, Wasowicz W. Source: Neoplasma. 2002; 49(4): 209-16. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12382017&dopt=Abstract
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Genetic polymorphisms of alcohol and aldehyde dehydrogenases and glutathione Stransferase M1 and drinking, smoking, and diet in Japanese men with esophageal squamous cell carcinoma. Author(s): Yokoyama A, Kato H, Yokoyama T, Tsujinaka T, Muto M, Omori T, Haneda T, Kumagai Y, Igaki H, Yokoyama M, Watanabe H, Fukuda H, Yoshimizu H. Source: Carcinogenesis. 2002 November; 23(11): 1851-9. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12419833&dopt=Abstract
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Genotoxic effect of raw betel-nut extract in relation to endogenous glutathione levels and its mechanism of action in mammalian cells. Author(s): Kumpawat K, Deb S, Ray S, Chatterjee A. Source: Mutation Research. 2003 July 8; 538(1-2): 1-12. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12834749&dopt=Abstract
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Genotypes of the glutathione S-transferase superfamily do not correlate with outcome of childhood acute lymphoblastic leukemia. Author(s): Sala A, Lanciotti M, Valsecchi MG, di Michele P, Dufour C, Haupt R, Basso G, Rizzari C, Biondi A. Source: Leukemia : Official Journal of the Leukemia Society of America, Leukemia Research Fund, U.K. 2003 May; 17(5): 981-3. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12750715&dopt=Abstract
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Glucose toxicity in beta-cells: type 2 diabetes, good radicals gone bad, and the glutathione connection. Author(s): Robertson RP, Harmon J, Tran PO, Tanaka Y, Takahashi H. Source: Diabetes. 2003 March; 52(3): 581-7. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12606496&dopt=Abstract
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Glutamine attenuates post-traumatic glutathione depletion in human muscle. Author(s): Flaring UB, Rooyackers OE, Wernerman J, Hammarqvist F. Source: Clinical Science (London, England : 1979). 2003 March; 104(3): 275-82. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12605586&dopt=Abstract
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Glutathione adducts of oxyeicosanoids. Author(s): Murphy RC, Zarini S. Source: Prostaglandins & Other Lipid Mediators. 2002 August; 68-69: 471-82. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12432937&dopt=Abstract
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Glutathione and glutathione S-transferases A1-1 and P1-1 in seminal plasma may play a role in protecting against oxidative damage to spermatozoa. Author(s): Raijmakers MT, Roelofs HM, Steegers EA, Steegers-Theunissen R RP, Mulder TP, Knapen MF, Wong WY, Peters WH. Source: Fertility and Sterility. 2003 January; 79(1): 169-72. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12524083&dopt=Abstract
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Glutathione and glutathione-related enzymes in colorectal cancer patients. Author(s): Saygili EI, Akcay T, Konukoglu D, Papilla C. Source: Journal of Toxicology and Environmental Health. Part A. 2003 March 14; 66(5): 411-5. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12712629&dopt=Abstract
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Glutathione and thioredoxin redox during differentiation in human colon epithelial (Caco-2) cells. Author(s): Nkabyo YS, Ziegler TR, Gu LH, Watson WH, Jones DP. Source: American Journal of Physiology. Gastrointestinal and Liver Physiology. 2002 December; 283(6): G1352-9. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12433666&dopt=Abstract
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Glutathione conjugates and their synthetic derivatives as inhibitors of glutathionedependent enzymes involved in cancer and drug resistance. Author(s): Burg D, Mulder GJ. Source: Drug Metabolism Reviews. 2002 November; 34(4): 821-63. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12487151&dopt=Abstract
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Glutathione cycle impairment mediates A beta-induced cell toxicity. Author(s): Cardoso SM, Oliveira CR. Source: Free Radical Research. 2003 March; 37(3): 241-50. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12688419&dopt=Abstract
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Glutathione depletion overcomes resistance to arsenic trioxide in arsenic-resistant cell lines. Author(s): Davison K, Cote S, Mader S, Miller WH. Source: Leukemia : Official Journal of the Leukemia Society of America, Leukemia Research Fund, U.K. 2003 May; 17(5): 931-40. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12750708&dopt=Abstract
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Glutathione distribution in normal and oxidatively stressed cells. Author(s): Ault JG, Lawrence DA. Source: Experimental Cell Research. 2003 April 15; 285(1): 9-14. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12681282&dopt=Abstract
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Glutathione disulfide induces apoptosis in U937 cells by a redox-mediated p38 MAP kinase pathway. Author(s): Filomeni G, Rotilio G, Ciriolo MR. Source: The Faseb Journal : Official Publication of the Federation of American Societies for Experimental Biology. 2003 January; 17(1): 64-6. Epub 2002 November 01. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12424221&dopt=Abstract
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Glutathione in defense and signaling: lessons from a small thiol. Author(s): Dickinson DA, Forman HJ. Source: Annals of the New York Academy of Sciences. 2002 November; 973: 488-504. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12485918&dopt=Abstract
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Glutathione in gingival crevicular fluid and its relation to local antioxidant capacity in periodontal health and disease. Author(s): Chapple IL, Brock G, Eftimiadi C, Matthews JB. Source: Molecular Pathology : Mp. 2002 December; 55(6): 367-73. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12456773&dopt=Abstract
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Glutathione metabolism and antioxidant enzymes in children with Down syndrome. Author(s): Pastore A, Tozzi G, Gaeta LM, Giannotti A, Bertini E, Federici G, Digilio MC, Piemonte F. Source: The Journal of Pediatrics. 2003 May; 142(5): 583-5. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12756395&dopt=Abstract
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Glutathione peroxidase (GPX) activity in seminal plasma of healthy and infertile males. Author(s): Giannattasio A, De Rosa M, Smeraglia R, Zarrilli S, Cimmino A, Di Rosario B, Ruggiero R, Colao A, Lombardi G. Source: J Endocrinol Invest. 2002 December; 25(11): 983-6. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12553559&dopt=Abstract
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Glutathione peroxidase 1 activity and cardiovascular events in patients with coronary artery disease. Author(s): Blankenberg S, Rupprecht HJ, Bickel C, Torzewski M, Hafner G, Tiret L, Smieja M, Cambien F, Meyer J, Lackner KJ; AtheroGene Investigators. Source: The New England Journal of Medicine. 2003 October 23; 349(17): 1605-13. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=14573732&dopt=Abstract
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Glutathione peroxidase 1 genotype is associated with an increased risk of coronary artery disease. Author(s): Winter JP, Gong Y, Grant PJ, Wild CP. Source: Coronary Artery Disease. 2003 April; 14(2): 149-53. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12655278&dopt=Abstract
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Glutathione peroxidase inhibits cell death and glial activation following experimental stroke. Author(s): Ishibashi N, Prokopenko O, Weisbrot-Lefkowitz M, Reuhl KR, Mirochnitchenko O. Source: Brain Research. Molecular Brain Research. 2002 December 30; 109(1-2): 34-44. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12531513&dopt=Abstract
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Glutathione peroxidase isoforms as part of the local antioxidative defense system in normal and Barrett's esophagus. Author(s): Mork H, Scheurlen M, Al-Taie O, Zierer A, Kraus M, Schottker K, Jakob F, Kohrle J. Source: International Journal of Cancer. Journal International Du Cancer. 2003 June 20; 105(3): 300-4. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12704661&dopt=Abstract
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Glutathione peroxidase levels throughout normal pregnancy and in pre-eclampsia. Author(s): Funai EF, MacKenzie A, Kadner SS, Roque H, Lee MJ, Kuczynski E. Source: J Matern Fetal Neonatal Med. 2002 November;12(5):322-6. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12607764&dopt=Abstract
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Glutathione peroxidase-1 expression enhances recovery of human breast carcinoma cells from hyperoxic cell cycle arrest. Author(s): Bilodeau JF, Patenaude A, Piedboeuf B, Carrier C, Petrov P, Faure R, Mirault ME. Source: Free Radical Biology & Medicine. 2002 November 1; 33(9): 1279-89. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12398936&dopt=Abstract
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Glutathione reductase of the malarial parasite Plasmodium falciparum: crystal structure and inhibitor development. Author(s): Sarma GN, Savvides SN, Becker K, Schirmer M, Schirmer RH, Karplus PA. Source: Journal of Molecular Biology. 2003 May 9; 328(4): 893-907. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12729762&dopt=Abstract
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Glutathione S-transferase (GST) polymorphisms as risk factors for cancer in a highly homogeneous population from southern Italy. Author(s): Sgambato A, Campisi B, Zupa A, Bochicchio A, Romano G, Tartarone A, Galasso R, Traficante A, Cittadini A. Source: Anticancer Res. 2002 November-December; 22(6B): 3647-52. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12552971&dopt=Abstract
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Glutathione S-transferase (GSTM1 and GSTT1)-dependent risk for colorectal cancer. Author(s): Laso N, Lafuente MJ, Mas S, Trias M, Ascaso C, Molina R, Ballesta A, Rodriguez F, Lafuente A. Source: Anticancer Res. 2002 November-December; 22(6A): 3399-403. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12530094&dopt=Abstract
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Glutathione S-transferase and O6-methylguanine DNA methyl transferase activities in patients with thyroid papillary carcinoma. Author(s): Dincer Y, Akcay T, Celebi N, Uslu I, Ozmen O, Hatemi H. Source: Cancer Investigation. 2002; 20(7-8): 965-71. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12449729&dopt=Abstract
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Glutathione S-transferase GSTP1 genotypes are associated with response to androgen ablation therapy in advanced prostate cancer. Author(s): Luscombe CJ, French ME, Liu S, Saxby MF, Farrell WE, Jones PW, Fryer AA, Strange RC. Source: Cancer Detection and Prevention. 2002; 26(5): 376-80. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12518868&dopt=Abstract
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Glutathione S-transferase isoenzyme profile in non-tumor and tumor human kidney tissue. Author(s): Simic T, Mimic-Oka J, Ille K, Dragicevic D, Savic-Radojevic A. Source: World Journal of Urology. 2003 May; 20(6): 385-91. Epub 2003 February 25. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12811499&dopt=Abstract
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Glutathione S-transferase M null homozygosity and risk of systemic lupus erythematosus associated with sun exposure: a possible gene-environment interaction for autoimmunity. Author(s): Fraser PA, Ding WZ, Mohseni M, Treadwell EL, Dooley MA, St Clair EW, Gilkeson GS, Cooper GS. Source: The Journal of Rheumatology. 2003 February; 30(2): 276-82. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12563680&dopt=Abstract
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Glutathione S-transferase M1 and T1 genetic polymorphisms, alcohol consumption and breast cancer risk. Author(s): Zheng T, Holford TR, Zahm SH, Owens PH, Boyle P, Zhang Y, Zhang B, Wise JP Sr, Stephenson LP, Ali-Osman F. Source: British Journal of Cancer. 2003 January 13; 88(1): 58-62. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12556960&dopt=Abstract
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Glutathione S-transferase M1 and T1 genotypes and endometriosis risk: a casecontrolled study. Author(s): Lin J, Zhang X, Qian Y, Ye Y, Shi Y, Xu K, Xu J. Source: Chinese Medical Journal. 2003 May; 116(5): 777-80. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12875700&dopt=Abstract
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Glutathione S-transferase M1 associated with cancer occurrence in Korean HNPCC families carrying the hMLH1/hMSH2 mutation. Author(s): Shin JH, Ku JL, Shin KH, Shin YK, Kang SB, Park JG. Source: Oncol Rep. 2003 March-April; 10(2): 483-6. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12579293&dopt=Abstract
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Glutathione S-transferase M1 polymorphism and the risk of lung cancer. Author(s): Mohr LC, Rodgers JK, Silvestri GA. Source: Anticancer Res. 2003 May-June; 23(3A): 2111-24. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12894585&dopt=Abstract
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Glutathione S-transferase M1, T1, and P1 polymorphisms and Parkinson's disease. Author(s): Kelada SN, Stapleton PL, Farin FM, Bammler TK, Eaton DL, Smith-Weller T, Franklin GM, Swanson PD, Longstreth WT Jr, Checkoway H. Source: Neuroscience Letters. 2003 January 30; 337(1): 5-8. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12524158&dopt=Abstract
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Glutathione s-transferase omega 1-1 is a target of cytokine release inhibitory drugs and may be responsible for their effect on interleukin-1beta posttranslational processing. Author(s): Laliberte RE, Perregaux DG, Hoth LR, Rosner PJ, Jordan CK, Peese KM, Eggler JF, Dombroski MA, Geoghegan KF, Gabel CA. Source: The Journal of Biological Chemistry. 2003 May 9; 278(19): 16567-78. Epub 2003 March 06. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12624100&dopt=Abstract
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Glutathione S-transferase P1 genetic polymorphisms and susceptibility to childhood acute lymphoblastic leukaemia. Author(s): Krajinovic M, Labuda D, Sinnett D. Source: Pharmacogenetics. 2002 November; 12(8): 655-8. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12439226&dopt=Abstract
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Glutathione S-transferase pi expression in nasopharyngeal cancer. Author(s): Jayasurya A, Yap WM, Tan NG, Tan BK, Bay BH. Source: Archives of Otolaryngology--Head & Neck Surgery. 2002 December; 128(12): 1396-9. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12479727&dopt=Abstract
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Glutathione S-transferase pi is upregulated in the stromal compartment of hormone independent prostate cancer. Author(s): Li M, Ittmann MM, Rowley DR, Knowlton AA, Vaid AK, Epner DE. Source: The Prostate. 2003 July 1; 56(2): 98-105. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12746833&dopt=Abstract
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Glutathione S-transferase polymorphisms in thyroid cancer patients. Author(s): Hernandez A, Cespedes W, Xamena N, Surralles J, Creus A, Galofre P, Marcos R. Source: Cancer Letters. 2003 February 10; 190(1): 37-44. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12536075&dopt=Abstract
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Glutathione S-transferase polymorphisms: susceptibility to migraine without aura. Author(s): Kusumi M, Ishizaki K, Kowa H, Adachi Y, Takeshima T, Sakai F, Nakashima K. Source: European Neurology. 2003; 49(4): 218-22. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12736537&dopt=Abstract
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Glutathione S-transferases and aromatic DNA adducts in smokers' bronchoalveolar macrophages. Author(s): Piipari R, Nurminen T, Savela K, Hirvonen A, Mantyla T, Anttila S. Source: Lung Cancer (Amsterdam, Netherlands). 2003 March; 39(3): 265-72. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12609564&dopt=Abstract
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Glutathione S-transferases M1-1 and T1-1 as risk modifiers for renal cell cancer associated with occupational exposure to chemicals. Author(s): Buzio L, De Palma G, Mozzoni P, Tondel M, Buzio C, Franchini I, Axelson O, Mutti A. Source: Occupational and Environmental Medicine. 2003 October; 60(10): 789-93. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=14504370&dopt=Abstract
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Glutathione synthetase deficiency: is gamma-glutamylcysteine accumulation a way to cope with oxidative stress in cells with insufficient levels of glutathione? Author(s): Ristoff E, Hebert C, Njalsson R, Norgren S, Rooyackers O, Larsson A. Source: Journal of Inherited Metabolic Disease. 2002 November; 25(7): 577-84. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12638941&dopt=Abstract
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Glutathione transferase theta 1-1-dependent metabolism of the water disinfection byproduct bromodichloromethane. Author(s): Ross MK, Pegram RA. Source: Chemical Research in Toxicology. 2003 February; 16(2): 216-26. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12588193&dopt=Abstract
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Glutathione, glutathione-dependent enzymes and antioxidant status in erythrocytes from children treated with high-dose paracetamol. Author(s): Kozer E, Evans S, Barr J, Greenberg R, Soriano I, Bulkowstein M, Petrov I, Chen-Levi Z, Barzilay B, Berkovitch M. Source: British Journal of Clinical Pharmacology. 2003 March; 55(3): 234-40. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12630972&dopt=Abstract
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Glutathione: a marker and antioxidant for aging. Author(s): Singh RJ. Source: The Journal of Laboratory and Clinical Medicine. 2002 December; 140(6): 380-1. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12486403&dopt=Abstract
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Glutathione-dependent system of antioxidant defense in the placenta in preterm delivery. Author(s): Prokopenko VM, Partsalis GK, Pavlova NG, Burmistrov SO, Arutyunyan AV. Source: Bulletin of Experimental Biology and Medicine. 2002 May; 133(5): 442-3. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12420055&dopt=Abstract
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Glutathione-related enzymes in cell cultures from different regions of human epididymis. Author(s): Montiel EE, Huidobro CC, Castellon EA. Source: Archives of Andrology. 2003 March-April; 49(2): 95-105. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12623745&dopt=Abstract
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Glutathione-S-transferases M1 (GSTM1) and GSTT1 genotype, smoking, consumption of alcohol and tea and risk of esophageal and stomach cancers: a casecontrol study of a high-incidence area in Jiangsu Province, China. Author(s): Gao CM, Takezaki T, Wu JZ, Li ZY, Liu YT, Li SP, Ding JH, Su P, Hu X, Xu TL, Sugimura H, Tajima K. Source: Cancer Letters. 2002 December 15; 188(1-2): 95-102. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12406553&dopt=Abstract
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Glutathione-thiyl radical scavenging and transferase properties of human glutaredoxin (thioltransferase). Potential role in redox signal transduction. Author(s): Starke DW, Chock PB, Mieyal JJ. Source: The Journal of Biological Chemistry. 2003 April 25; 278(17): 14607-13. Epub 2003 January 29. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12556467&dopt=Abstract
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Heme oxygenase-1 induction by endogenous nitric oxide: influence of intracellular glutathione. Author(s): Andre M, Felley-Bosco E. Source: Febs Letters. 2003 July 10; 546(2-3): 223-7. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12832044&dopt=Abstract
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High blood glutathione levels accompany excellent physical and mental health in women ages 60 to 103 years. Author(s): Lang CA, Mills BJ, Lang HL, Liu MC, Usui WM, Richie J Jr, Mastropaolo W, Murrell SA. Source: The Journal of Laboratory and Clinical Medicine. 2002 December; 140(6): 413-7. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12486409&dopt=Abstract
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Higher glutathione transferase GSTM1 0/0 genotype frequency in young thyroid carcinoma patients. Author(s): Canbay E, Dokmetas S, Canbay EI, Sen M, Bardakci F. Source: Current Medical Research and Opinion. 2003; 19(2): 102-6. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12740153&dopt=Abstract
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Homocysteine and cysteine - albumin binding in homocystinuria: assessment of cysteine status and implications for glutathione synthesis? Author(s): Hargreaves IP, Lee PJ, Briddon A. Source: Amino Acids. 2002; 22(2): 109-18. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12395179&dopt=Abstract
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HPV antibody detection by ELISA with capsid protein L1 fused to glutathione Stransferase. Author(s): Sehr P, Muller M, Hopfl R, Widschwendter A, Pawlita M. Source: Journal of Virological Methods. 2002 October; 106(1): 61-70. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12367730&dopt=Abstract
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Human glutathione-dependent formaldehyde dehydrogenase. Structural changes associated with ternary complex formation. Author(s): Sanghani PC, Bosron WF, Hurley TD. Source: Biochemistry. 2002 December 24; 41(51): 15189-94. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12484756&dopt=Abstract
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Human skeletal muscle interstitial glutathione levels are elevated in comparison to adipose tissue and blood plasma. Author(s): Tonkonogi M, Henriksson J, Cotgreave IA. Source: Archives of Biochemistry and Biophysics. 2003 May 1; 413(1): 147-9. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12706352&dopt=Abstract
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Hydrogen-peroxide-induced heme degradation in red blood cells: the protective roles of catalase and glutathione peroxidase. Author(s): Nagababu E, Chrest FJ, Rifkind JM. Source: Biochimica Et Biophysica Acta. 2003 March 17; 1620(1-3): 211-7. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12595091&dopt=Abstract
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Hypermethylation of the human glutathione S-transferase-pi gene (GSTP1) CpG island is present in a subset of proliferative inflammatory atrophy lesions but not in normal or hyperplastic epithelium of the prostate: a detailed study using lasercapture microdissection. Author(s): Nakayama M, Bennett CJ, Hicks JL, Epstein JI, Platz EA, Nelson WG, De Marzo AM. Source: American Journal of Pathology. 2003 September; 163(3): 923-33. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12937133&dopt=Abstract
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Hyperoxemia caused by resuscitation with pure oxygen may alter intracellular redox status by increasing oxidized glutathione in asphyxiated newly born infants. Author(s): Vento M, Asensi M, Sastre J, Lloret A, Garcia-Sala F, Minana JB, Vina J. Source: Semin Perinatol. 2002 December; 26(6): 406-10. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12537311&dopt=Abstract
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Identification of glutathione conjugates of troglitazone in human hepatocytes. Author(s): Prabhu S, Fackett A, Lloyd S, McClellan HA, Terrell CM, Silber PM, Li AP. Source: Chemico-Biological Interactions. 2002 November 10; 142(1-2): 83-97. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12399157&dopt=Abstract
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Identification of glutathione modifications by cigarette smoke. Author(s): Reddy S, Finkelstein EI, Wong PS, Phung A, Cross CE, van der Vliet A. Source: Free Radical Biology & Medicine. 2002 December 1; 33(11): 1490-8. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12446206&dopt=Abstract
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Identification of thiols and glutathione conjugates of depsipeptide FK228 (FR901228), a novel histone protein deacetylase inhibitor, in the blood. Author(s): Xiao JJ, Byrd J, Marcucci G, Grever M, Chan KK. Source: Rapid Communications in Mass Spectrometry : Rcm. 2003; 17(8): 757-66. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12672127&dopt=Abstract
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Identification, characterization, and properties of a class alpha microsomal glutathione S-transferase. Author(s): Prabhu KS, Reddy PV, Liken AD, Jones EC, Yennawar HP, Reddy CC. Source: Advances in Experimental Medicine and Biology. 2003; 525: 189-92. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12751765&dopt=Abstract
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Impaired glutathione reductase activity and levels of collagenase and elastase in synovial fluid in rheumatoid arthritis. Author(s): Bazzichi L, Ciompi ML, Betti L, Rossi A, Melchiorre D, Fiorini M, Giannaccini G, Lucacchini A. Source: Clin Exp Rheumatol. 2002 November-December; 20(6): 761-6. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12508766&dopt=Abstract
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Increased expression of alpha-1-antitrypsin, glutathione S-transferase pi and vascular endothelial growth factor in human pancreatic adenocarcinoma. Author(s): Trachte AL, Suthers SE, Lerner MR, Hanas JS, Jupe ER, Sienko AE, Adesina AM, Lightfoot SA, Brackett DJ, Postier RG. Source: American Journal of Surgery. 2002 December; 184(6): 642-7; Discussion 647-8. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12488200&dopt=Abstract
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Individual sensitivity to DNA damage induced by styrene in vitro: influence of cytochrome p450, epoxide hydrolase and glutathione S-transferase genotypes. Author(s): Laffon B, Perez-Cadahia B, Pasaro E, Mendez J. Source: Toxicology. 2003 April 15; 186(1-2): 131-41. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12604177&dopt=Abstract
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Inevitable glutathione, then and now. Author(s): Rana SV, Allen T, Singh R. Source: Indian J Exp Biol. 2002 June; 40(6): 706-16. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12587718&dopt=Abstract
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Influence of clinical factors, drug use, and food intake on the glutathione system. Author(s): Shirin H, Pinto JT, Moss SF. Source: Gut. 2003 January; 52(1): 154; Author Reply 154-5. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12477783&dopt=Abstract
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Inhibition of glutathione synthesis reverses Bcl-2-mediated cisplatin resistance. Author(s): Rudin CM, Yang Z, Schumaker LM, VanderWeele DJ, Newkirk K, Egorin MJ, Zuhowski EG, Cullen KJ. Source: Cancer Research. 2003 January 15; 63(2): 312-8. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12543781&dopt=Abstract
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Inhibition of human glutathione S-transferase P1-1 by the flavonoid quercetin. Author(s): van Zanden JJ, Ben Hamman O, van Iersel ML, Boeren S, Cnubben NH, Lo Bello M, Vervoort J, van Bladeren PJ, Rietjens IM. Source: Chemico-Biological Interactions. 2003 May 6; 145(2): 139-48. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12686490&dopt=Abstract
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Interaction between nitric oxide and subsets of human T lymphocytes with differences in glutathione metabolism. Author(s): Roozendaal R, Kauffman HF, Dijkhuis AJ, Ommen ET, Postma DS, de Monchy JG, Vellenga E. Source: Immunology. 2002 November; 107(3): 334-9. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12423309&dopt=Abstract
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Interactions of peroxynitrite and other nitrating substances with human platelets: the role of glutathione and peroxynitrite permeability. Author(s): Lufrano M, Balazy M. Source: Biochemical Pharmacology. 2003 February 15; 65(4): 515-23. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12566078&dopt=Abstract
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Interleukin-8, nitric oxide and glutathione status in proliferative vitreoretinopathy and proliferative diabetic retinopathy. Author(s): Cicik E, Tekin H, Akar S, Ekmekci OB, Donma O, Koldas L, Ozkan S. Source: Ophthalmic Research. 2003 September-October; 35(5): 251-5. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12920337&dopt=Abstract
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Intermediate structural states involved in MRP1-mediated drug transport. Role of glutathione. Author(s): Manciu L, Chang XB, Buyse F, Hou YX, Gustot A, Riordan JR, Ruysschaert JM. Source: The Journal of Biological Chemistry. 2003 January 31; 278(5): 3347-56. Epub 2002 November 06. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12424247&dopt=Abstract
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Intracellular delivery of glutathione S-transferase into mammalian cells. Author(s): Namiki S, Tomida T, Tanabe M, Iino M, Hirose K. Source: Biochemical and Biophysical Research Communications. 2003 June 6; 305(3): 592-7. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12763035&dopt=Abstract
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Intracellular glutathione and lipid peroxide availability and the secretion of vasoactive substances by human umbilical vein endothelial cells after incubation with TNF-alpha. Author(s): Scalera F. Source: European Journal of Clinical Investigation. 2003 February; 33(2): 176-82. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12588293&dopt=Abstract
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Levels of malondialdehyde, glutathione and ascorbic acid in idiopathic thrombocytopaenic purpura. Author(s): Polat G, Tamer L, Tanriverdi K, Gurkan E, Baslamisli F, Atik U. Source: East Afr Med J. 2002 August; 79(8): 446-9. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12638848&dopt=Abstract
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Lipoic acid and vitamin C potentiate nitric oxide synthesis in human aortic endothelial cells independently of cellular glutathione status. Author(s): Visioli F, Smith A, Zhang W, Keaney JF Jr, Hagen T, Frei B. Source: Redox Report : Communications in Free Radical Research. 2002; 7(4): 223-7. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12396668&dopt=Abstract
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Liver disease in pediatric patients with cystic fibrosis is associated with glutathione S-transferase P1 polymorphism. Author(s): Henrion-Caude A, Flamant C, Roussey M, Housset C, Flahault A, Fryer AA, Chadelat K, Strange RC, Clement A. Source: Hepatology (Baltimore, Md.). 2002 October; 36(4 Pt 1): 913-7. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12297838&dopt=Abstract
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Low activity of superoxide dismutase and high activity of glutathione reductase in erythrocytes from centenarians. Author(s): Andersen HR, Jeune B, Nybo H, Nielsen JB, Andersen-Ranberg K, Grandjean P. Source: Age and Ageing. 1998 September; 27(5): 643-8. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12675104&dopt=Abstract
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Low blood glutathione levels in acute myocardial infarction. Author(s): Kharb S. Source: Indian Journal of Medical Sciences. 2003 August; 57(8): 335-7. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12944689&dopt=Abstract
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Manganese superoxide dismutase, glutathione peroxidase, and total radical trapping antioxidant capacity in active rheumatoid arthritis. Author(s): De Leo ME, Tranghese A, Passantino M, Mordente A, Lizzio MM, Galeotti T, Zoli A. Source: The Journal of Rheumatology. 2002 October; 29(10): 2245-6. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12375348&dopt=Abstract
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Measurement of plasma glutathione S-transferase in hepatocellular damage in preeclampsia. Author(s): Kumtepe Y, Borekci B, Aksoy H, Altinkaynak K, Ingec M, Ozdiller O. Source: J Int Med Res. 2002 September-October; 30(5): 483-7. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12449517&dopt=Abstract
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Mechanisms and physiological significance of the transport of the glutathione conjugate of 4-hydroxynonenal in human lens epithelial cells. Author(s): Sharma R, Yang Y, Sharma A, Dwivedi S, Popov VL, Boor PJ, Singhal SS, Awasthi S, Awasthi YC. Source: Investigative Ophthalmology & Visual Science. 2003 August; 44(8): 3438-49. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12882793&dopt=Abstract
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Mercury toxicity and antioxidants: Part 1: role of glutathione and alpha-lipoic acid in the treatment of mercury toxicity. Author(s): Patrick L. Source: Alternative Medicine Review : a Journal of Clinical Therapeutic. 2002 December; 7(6): 456-71. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12495372&dopt=Abstract
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Microsomal epoxide hydrolase and glutathione S-transferase polymorphisms in relation to laryngeal carcinoma risk. Author(s): To-Figueras J, Gene M, Gomez-Catalan J, Pique E, Borrego N, Caballero M, Cruellas F, Raya A, Dicenta M, Corbella J. Source: Cancer Letters. 2002 December 10; 187(1-2): 95-101. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12359356&dopt=Abstract
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Modeling the metabolic competency of glutathione S-transferases using genetically modified cell lines. Author(s): Townsend AJ, Kabler SL, Doehmer J, Morrow CS. Source: Toxicology. 2002 December 27; 181-182: 265-9. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12505323&dopt=Abstract
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Moderate coffee consumption increases plasma glutathione but not homocysteine in healthy subjects. Author(s): Esposito F, Morisco F, Verde V, Ritieni A, Alezio A, Caporaso N, Fogliano V. Source: Alimentary Pharmacology & Therapeutics. 2003 February 15; 17(4): 595-601. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12622769&dopt=Abstract
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Mu class glutathione S-transferase mRNA isoform expression in acute lymphoblastic leukaemia. Author(s): Kearns PR, Chrzanowska-Lightowlers ZM, Pieters R, Veerman A, Hall AG. Source: British Journal of Haematology. 2003 January; 120(1): 80-8. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12492580&dopt=Abstract
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N-acetyltransferase (NAT1, NAT2) and glutathione S-transferase (GSTM1, GSTT1) polymorphisms in breast cancer. Author(s): Lee KM, Park SK, Kim SU, Doll MA, Yoo KY, Ahn SH, Noh DY, Hirvonen A, Hein DW, Kang D. Source: Cancer Letters. 2003 July 10; 196(2): 179-86. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12860276&dopt=Abstract
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Naturally occurring Phe151Leu substitution near a conserved folding module lowers stability of glutathione transferase P1-1. Author(s): Lin HJ, Johansson AS, Stenberg G, Materi AM, Park JM, Dai A, Zhou H, Gim JS, Kau IH, Hardy SI, Parker MW, Mannervik B. Source: Biochimica Et Biophysica Acta. 2003 June 26; 1649(1): 16-23. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12818186&dopt=Abstract
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Negative prognostic value of glutathione S-transferase (GSTM1 and GSTT1) deletions in adult acute myeloid leukemia. Author(s): Voso MT, D'Alo' F, Putzulu R, Mele L, Scardocci A, Chiusolo P, Latagliata R, Lo-Coco F, Rutella S, Pagano L, Hohaus S, Leone G. Source: Blood. 2002 October 15; 100(8): 2703-7. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12351375&dopt=Abstract
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Nitric oxide synthase is present in the cerebrospinal fluid of patients with active multiple sclerosis and is associated with increases in cerebrospinal fluid protein nitrotyrosine and S-nitrosothiols and with changes in glutathione levels. Author(s): Calabrese V, Scapagnini G, Ravagna A, Bella R, Foresti R, Bates TE, Giuffrida Stella AM, Pennisi G. Source: Journal of Neuroscience Research. 2002 November 15; 70(4): 580-7. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12404512&dopt=Abstract
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Novel class of bivalent glutathione S-transferase inhibitors. Author(s): Lyon RP, Hill JJ, Atkins WM. Source: Biochemistry. 2003 September 9; 42(35): 10418-28. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12950168&dopt=Abstract
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Novel polymorphisms in the glutathione transferase superfamily. Author(s): Mannervik B. Source: Pharmacogenetics. 2003 March; 13(3): 127-8. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12618589&dopt=Abstract
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Overexpression of Cu-Zn superoxide dismutase protects neuroblastoma cells against dopamine cytotoxicity accompanied by increase in their glutathione level. Author(s): Haque ME, Asanuma M, Higashi Y, Miyazaki I, Tanaka K, Ogawa N. Source: Neuroscience Research. 2003 September; 47(1): 31-7. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12941444&dopt=Abstract
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Overexpression of glutathione S-transferase A1-1 in ECV 304 cells protects against busulfan mediated G2-arrest and induces tissue factor expression. Author(s): Ritter CA, Sperker B, Grube M, Dressel D, Kunert-Keil C, Kroemer HK. Source: British Journal of Pharmacology. 2002 December; 137(7): 1100-6. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12429583&dopt=Abstract
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Oxathiolene oxides: a novel family of compounds that induce ferritin, glutathione Stransferase, and other proteins of the phase II response. Author(s): Pietsch EC, Hurley AL, Scott EE, Duckworth BP, Welker ME, Leone-Kabler S, Townsend AJ, Torti FM, Torti SV. Source: Biochemical Pharmacology. 2003 April 15; 65(8): 1261-9. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12694867&dopt=Abstract
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Pharmacological action and therapeutic effects of glutathione on hypokinetic spermatozoa for enzymatic-dependent pathologies and correlated genetic aspects. Author(s): Tripodi L, Tripodi A, Mammi C, Pulle C, Cremonesi F. Source: Clin Exp Obstet Gynecol. 2003; 30(2-3): 130-6. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12854860&dopt=Abstract
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Phenotyping of human glutathione S-transferase hGSTT1-1: a comparison of two ex vivo routine procedures. Author(s): Muller M, Bunger J, Voss M, Westphal G, Ruhnau P, Hallier E. Source: Archives of Toxicology. 2002 November; 76(11): 634-42. Epub 2002 August 09. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12415426&dopt=Abstract
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Physiological role of S-formylglutathione hydrolase in C(1) metabolism of the methylotrophic yeast Candida boidinii. Author(s): Yurimoto H, Lee B, Yano T, Sakai Y, Kato N. Source: Microbiology (Reading, England). 2003 August; 149(Pt 8): 1971-9. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12904537&dopt=Abstract
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Pink-eyed dilution protein modulates arsenic sensitivity and intracellular glutathione metabolism. Author(s): Staleva L, Manga P, Orlow SJ. Source: Molecular Biology of the Cell. 2002 December; 13(12): 4206-20. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12475946&dopt=Abstract
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Plasma creatine kinase activity and glutathione after eccentric exercise. Author(s): Lee J, Clarkson PM. Source: Medicine and Science in Sports and Exercise. 2003 June; 35(6): 930-6. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12783040&dopt=Abstract
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Plasma selenium and plasma and erythrocyte glutathione peroxidase activity increase with estrogen during the menstrual cycle. Author(s): Ha EJ, Smith AM. Source: Journal of the American College of Nutrition. 2003 February; 22(1): 43-51. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12569113&dopt=Abstract
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Platinum/paclitaxel-based chemotherapy in advanced ovarian carcinoma: glutathione S-transferase genetic polymorphisms as predictive biomarkers of disease outcome. Author(s): Medeiros R, Pereira D, Afonso N, Palmeira C, Faleiro C, Afonso-Lopes C, Freitas-Silva M, Vasconcelos A, Costa S, Osorio T, Lopes C. Source: International Journal of Clinical Oncology / Japan Society of Clinical Oncology. 2003 June; 8(3): 156-61. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12851839&dopt=Abstract
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Polymorphism of glutathione S-transferase T1, M1 and P1 genes in a Shanghai population: patients with occupational or non-occupational bladder cancer. Author(s): Ma QW, Lin GF, Chen JG, Shen JH. Source: Biomed Environ Sci. 2002 September; 15(3): 253-60. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12500666&dopt=Abstract
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Polymorphisms in XRCC1 and glutathione S-transferase genes and hepatitis B-related hepatocellular carcinoma. Author(s): Yu MW, Yang SY, Pan IJ, Lin CL, Liu CJ, Liaw YF, Lin SM, Chen PJ, Lee SD, Chen CJ. Source: Journal of the National Cancer Institute. 2003 October 1; 95(19): 1485-8. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=14519756&dopt=Abstract
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Polymorphisms of glutathione S-transferase mu1 (GSTM1) and theta1 (GSTT1) genes in multiple myeloma. Author(s): Ortega MM, Nascimento H, Melo MB, Teori MT, Costa FF, Lima CS. Source: Acta Haematologica. 2003; 109(2): 108-9. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12624497&dopt=Abstract
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Polymorphisms of the glutathione S-transferase P1 gene and head and neck cancer susceptibility. Author(s): Oude Ophuis MB, Roelofs HM, van den Brandt PA, Peters WH, Manni JJ. Source: Head & Neck. 2003 January; 25(1): 37-43. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12478542&dopt=Abstract
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Possible function of two insect phospholipid-hydroperoxide glutathione peroxidases. Author(s): Li D, Blasevich F, Theopold U, Schmidt O. Source: Journal of Insect Physiology. 2003 January; 49(1): 1-9. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12770011&dopt=Abstract
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Possible influence of glutathione S-transferase GSTT1 null genotype on age of onset of sporadic colorectal adenocarcinoma. Author(s): Nascimento H, Coy CS, Teori MT, Boin IF, Goes JR, Costa FF, Lima CS. Source: Diseases of the Colon and Rectum. 2003 April; 46(4): 510-5. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12682546&dopt=Abstract
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Possible signaling by glutathione and its novel analogue through potent stimulation of fontocortical G proteins in normal aging and in Alzheimer's disease. Author(s): Karelson E, Mahlapuu R, Zilmer M, Soomets U, Bogdanovic N, Langel U. Source: Annals of the New York Academy of Sciences. 2002 November; 973: 537-40. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12485924&dopt=Abstract
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Potentiation of tumour apoptosis by human growth hormone via glutathione production and decreased NF-kappaB activity. Author(s): Cherbonnier C, Deas O, Carvalho G, Vassal G, Durrbach A, Haeffner A, Charpentier B, Benard J, Hirsch F. Source: British Journal of Cancer. 2003 September 15; 89(6): 1108-15. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12966434&dopt=Abstract
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Preservation of extracellular glutathione by an astrocyte derived factor with properties comparable to extracellular superoxide dismutase. Author(s): Stewart VC, Stone R, Gegg ME, Sharpe MA, Hurst RD, Clark JB, Heales SJ. Source: Journal of Neurochemistry. 2002 November; 83(4): 984-91. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12421371&dopt=Abstract
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Production of intracellular 35S-glutathione by rat and human hepatocytes for the quantification of xenobiotic reactive intermediates. Author(s): Hartman NR, Cysyk RL, Bruneau-Wack C, Thenot JP, Parker RJ, Strong JM. Source: Chemico-Biological Interactions. 2002 November 10; 142(1-2): 43-55. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12399154&dopt=Abstract
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Prognostic potential of glutathione S-transferase M1 and T1 null genotypes for gastric cancer progression. Author(s): Choi SC, Yun KJ, Kim TH, Kim HJ, Park SG, Oh GJ, Chae SC, Oh GJ, Nah YH, Kim JJ, Chung HT. Source: Cancer Letters. 2003 June 10; 195(2): 169-75. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12767525&dopt=Abstract
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Prognostic significance of mutant p53 protein, P-glycoprotein and glutathione Stransferase-pi in patients with unresectable non-small cell lung cancer. Author(s): Miyatake K, Gemba K, Ueoka H, Nishii K, Kiura K, Tabata M, Shibayama T, Takigawa N, Kawaraya M, Tanimoto M. Source: Anticancer Res. 2003 May-June; 23(3C): 2829-36. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12926120&dopt=Abstract
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Programmed delivery of novel functional groups to the alpha class glutathione transferases. Author(s): Hakansson S, Viljanen J, Broo KS. Source: Biochemistry. 2003 September 2; 42(34): 10260-8. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12939155&dopt=Abstract
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Prospective assessment of the predictive value of alpha-glutathione S-transferase for intestinal ischemia. Author(s): Gearhart SL, Delaney CP, Senagore AJ, Banbury MK, Remzi FH, Kiran RP, Fazio VW. Source: The American Surgeon. 2003 April; 69(4): 324-9; Discussion 329. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12716091&dopt=Abstract
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Pt(II) complexes with N-(3-pyridyl)-2-(4-(trifluoromethyl)phenyl)diazenecarboxamide and their reactions with glutathione. Author(s): Grabner S, Kosmrlj J, Bukovec N, Cemazar M. Source: Journal of Inorganic Biochemistry. 2003 June 1; 95(2-3): 105-12. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12763654&dopt=Abstract
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PU.1 regulates glutathione peroxidase expression in neutrophils. Author(s): Throm SL, Klemsz MJ. Source: Journal of Leukocyte Biology. 2003 July; 74(1): 111-7. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12832449&dopt=Abstract
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Pyocyanin induces oxidative stress in human endothelial cells and modulates the glutathione redox cycle. Author(s): Muller M. Source: Free Radical Biology & Medicine. 2002 December 1; 33(11): 1527-33. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12446210&dopt=Abstract
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Rapid spectrophotometric method for serum glutathione S-transferases activity. Author(s): Habdous M, Vincent-Viry M, Visvikis S, Siest G. Source: Clinica Chimica Acta; International Journal of Clinical Chemistry. 2002 December; 326(1-2): 131-42. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12417104&dopt=Abstract
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Reconstitution of galectin-3 alters glutathione content and potentiates TRAILinduced cytotoxicity by dephosphorylation of Akt. Author(s): Lee YJ, Song YK, Song JJ, Siervo-Sassi RR, Kim HR, Li L, Spitz DR, Lokshin A, Kim JH. Source: Experimental Cell Research. 2003 August 1; 288(1): 21-34. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12878156&dopt=Abstract
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Redox regulation of homocysteine-dependent glutathione synthesis. Author(s): Vitvitsky V, Mosharov E, Tritt M, Ataullakhanov F, Banerjee R. Source: Redox Report : Communications in Free Radical Research. 2003; 8(1): 57-63. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12631446&dopt=Abstract
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Reduction of S-nitrosoglutathione by human alcohol dehydrogenase 3 is an irreversible reaction as analysed by electrospray mass spectrometry. Author(s): Hedberg JJ, Griffiths WJ, Nilsson SJ, Hoog JO. Source: European Journal of Biochemistry / Febs. 2003 March; 270(6): 1249-56. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12631283&dopt=Abstract
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Regulation of expression of the phospholipid hydroperoxide/sperm nucleus glutathione peroxidase gene. Tissue-specific expression pattern and identification of functional cis- and trans-regulatory elements. Author(s): Borchert A, Savaskan NE, Kuhn H. Source: The Journal of Biological Chemistry. 2003 January 24; 278(4): 2571-80. Epub 2002 November 08. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12427732&dopt=Abstract
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Relationship between expression of O6-methylguanine-DNA methyltransferase, glutathione-S-transferase pi in glioblastoma and the survival of the patients treated with nimustine hydrochloride: an immunohistochemical analysis. Author(s): Anda T, Shabani HK, Tsunoda K, Tokunaga Y, Kaminogo M, Shibata S, Hayashi T, Iseki M. Source: Neurological Research. 2003 April; 25(3): 241-8. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12739231&dopt=Abstract
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Relationship between intracellular glutathione level and the mode of cell death induced by pingyangmycin. Author(s): Tai KW, Lii CK, Chou MY, Chang YC. Source: Oral Oncology. 2003 January; 39(1): 13-8. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12457716&dopt=Abstract
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Reporter gene transactivation by human p53 is inhibited in thioredoxin reductase null yeast by a mechanism associated with thioredoxin oxidation and independent of changes in the redox state of glutathione. Author(s): Merwin JR, Mustacich DJ, Muller EG, Pearson GD, Merrill GF. Source: Carcinogenesis. 2002 October; 23(10): 1609-15. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12376468&dopt=Abstract
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Reproductive factors, glutathione S-transferase M1 and T1 genetic polymorphism and breast cancer risk. Author(s): Park SK, Kang D, Noh DY, Lee KM, Kim SU, Choi JY, Choi IM, Ahn SH, Choe KJ, Hirvonen A, Strickland PT, Yoo KY. Source: Breast Cancer Research and Treatment. 2003 March; 78(1): 89-96. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12611461&dopt=Abstract
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Resistance to phorbol 12-myristate 13-acetate-induced cell growth arrest in an HL60 cell line chronically exposed to a glutathione S-transferase pi inhibitor. Author(s): Gate L, Lunk A, Tew KD. Source: Biochemical Pharmacology. 2003 May 15; 65(10): 1611-22. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12754097&dopt=Abstract
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Reversal of multiple drug resistance in cholangiocarcinoma by the glutathione Stransferase-pi-specific inhibitor O1-hexadecyl-gamma-glutamyl-S-benzylcysteinyl-Dphenylglycine ethylester. Author(s): Nakajima T, Takayama T, Miyanishi K, Nobuoka A, Hayashi T, Abe T, Kato J, Sakon K, Naniwa Y, Tanabe H, Niitsu Y. Source: The Journal of Pharmacology and Experimental Therapeutics. 2003 September; 306(3): 861-9. Epub 2003 June 12. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12805482&dopt=Abstract
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Risk of atherosclerosis: interaction of smoking and glutathione S-transferase genes. Author(s): Olshan AF, Li R, Pankow JS, Bray M, Tyroler HA, Chambless LE, Boerwinkle E, Pittman GS, Bell DA. Source: Epidemiology (Cambridge, Mass.). 2003 May; 14(3): 321-7. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12859033&dopt=Abstract
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Role for recombinant gamma-glutamyltransferase from Treponema denticola in glutathione metabolism. Author(s): Chu L, Xu X, Dong Z, Cappelli D, Ebersole JL. Source: Infection and Immunity. 2003 January; 71(1): 335-42. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12496183&dopt=Abstract
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Role of cystine transport in intracellular glutathione level and cisplatin resistance in human ovarian cancer cell lines. Author(s): Okuno S, Sato H, Kuriyama-Matsumura K, Tamba M, Wang H, Sohda S, Hamada H, Yoshikawa H, Kondo T, Bannai S. Source: British Journal of Cancer. 2003 March 24; 88(6): 951-6. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12644836&dopt=Abstract
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Role of glutathione in macrophage control of mycobacteria. Author(s): Venketaraman V, Dayaram YK, Amin AG, Ngo R, Green RM, Talaue MT, Mann J, Connell ND. Source: Infection and Immunity. 2003 April; 71(4): 1864-71. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12654802&dopt=Abstract
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Role of reduced glutathione efflux in apoptosis of immortalized human keratinocytes induced by UVA. Author(s): He YY, Huang JL, Ramirez DC, Chignell CF. Source: The Journal of Biological Chemistry. 2003 March 7; 278(10): 8058-64. Epub 2002 December 26. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12502708&dopt=Abstract
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Sanguinarine-induced apoptosis is associated with an early and severe cellular glutathione depletion. Author(s): Debiton E, Madelmont JC, Legault J, Barthomeuf C. Source: Cancer Chemotherapy and Pharmacology. 2003 June; 51(6): 474-82. Epub 2003 April 17. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12700925&dopt=Abstract
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Screening for recombinant glutathione transferases active with monochlorobimane. Author(s): Eklund BI, Edalat M, Stenberg G, Mannervik B. Source: Analytical Biochemistry. 2002 October 1; 309(1): 102-8. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12381368&dopt=Abstract
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Selenium supplementation acting through the induction of thioredoxin reductase and glutathione peroxidase protects the human endothelial cell line EAhy926 from damage by lipid hydroperoxides. Author(s): Lewin MH, Arthur JR, Riemersma RA, Nicol F, Walker SW, Millar EM, Howie AF, Beckett GJ. Source: Biochimica Et Biophysica Acta. 2002 December 16; 1593(1): 85-92. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12431787&dopt=Abstract
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Sensitivity of the 2-oxoglutarate carrier to alcohol intake contributes to mitochondrial glutathione depletion. Author(s): Coll O, Colell A, Garcia-Ruiz C, Kaplowitz N, Fernandez-Checa JC. Source: Hepatology (Baltimore, Md.). 2003 September; 38(3): 692-702. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12939596&dopt=Abstract
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Serum glutathione-S-transferase and glutathione reductase activity in head and neck cancer patients. Author(s): Patel BP, Raval GN, Rawal RM, Patel JB, Sainger RN, Patel MM, Shah MH, Patel DD, Patel PS. Source: Neoplasma. 2002; 49(4): 260-6. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12382026&dopt=Abstract
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Significance of nuclear glutathione S-transferase pi in resistance to anti-cancer drugs. Author(s): Goto S, Kamada K, Soh Y, Ihara Y, Kondo T. Source: Japanese Journal of Cancer Research : Gann. 2002 September; 93(9): 1047-56. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12359059&dopt=Abstract
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S-nitrosoglutathione reduces asymptomatic embolization after carotid angioplasty. Author(s): Kaposzta Z, Clifton A, Molloy J, Martin JF, Markus HS. Source: Circulation. 2002 December 10; 106(24): 3057-62. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12473551&dopt=Abstract
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S-nitrosoglutathione reductase activity of human and yeast glutathione-dependent formaldehyde dehydrogenase and its nuclear and cytoplasmic localisation. Author(s): Fernandez MR, Biosca JA, Pares X. Source: Cellular and Molecular Life Sciences : Cmls. 2003 May; 60(5): 1013-8. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12827289&dopt=Abstract
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Structural requirements for functional interaction of glutathione tripeptide analogs with the human multidrug resistance protein 1 (MRP1). Author(s): Leslie EM, Bowers RJ, Deeley RG, Cole SP. Source: The Journal of Pharmacology and Experimental Therapeutics. 2003 February; 304(2): 643-53. Erratum In: J Pharmacol Exp Ther. 2003 May; 305(2): 798. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12538817&dopt=Abstract
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Structure of a Drosophila sigma class glutathione S-transferase reveals a novel active site topography suited for lipid peroxidation products. Author(s): Agianian B, Tucker PA, Schouten A, Leonard K, Bullard B, Gros P. Source: Journal of Molecular Biology. 2003 February 7; 326(1): 151-65. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12547198&dopt=Abstract
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Studies on the mechanism of the UVA light-dependent loss of glutathione reductase activity in human lenses. Author(s): Linetsky M, Hill JM, Chemoganskiy VG, Hu F, Ortwerth BJ. Source: Investigative Ophthalmology & Visual Science. 2003 September; 44(9): 3920-6. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12939310&dopt=Abstract
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Superoxide dismutase activity and glutathione system in erythrocytes of men with Behchet's disease. Author(s): Dincer Y, Alademir Z, Hamuryudan V, Fresko I, Akcay T. Source: The Tohoku Journal of Experimental Medicine. 2002 November; 198(3): 191-5. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12597246&dopt=Abstract
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Synthesis and characterization of 6-chloroacetyl-2-dimethylaminonaphthalene as a fluorogenic substrate and a mechanistic probe for glutathione transferases. Author(s): Svensson R, Greno C, Johansson AS, Mannervik B, Morgenstern R. Source: Analytical Biochemistry. 2002 December 15; 311(2): 171-8. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12470677&dopt=Abstract
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Targeting the mitochondria: an exciting new approach to myeloma therapy. Commentary re: N. J. Bahlis et al., Feasibility and correlates of arsenic trioxide combined with ascorbic acid-mediated depletion of intracellular glutathione for the treatment of relapsed/refractory multiple myeloma. Clin. Cancer Res., 8: 3658-3668, 2002. Author(s): Dalton WS. Source: Clinical Cancer Research : an Official Journal of the American Association for Cancer Research. 2002 December; 8(12): 3643-5. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12473572&dopt=Abstract
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The effect of s-nitroso-glutathione on platelet and leukocyte function during experimental extracorporeal circulation. Author(s): Adrian K, Skogby M, Friberg LG, Mellgren K. Source: Artificial Organs. 2003 June; 27(6): 570-5. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12780512&dopt=Abstract
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The effects of losartan and enalapril therapies on the levels of nitric oxide, malondialdehyde, and glutathione in patients with essential hypertension. Author(s): Donmez G, Derici U, Erbas D, Arinsoy T, Onk A, Sindel S, Hasanoglu E. Source: Japanese Journal of Physiology. 2002 October; 52(5): 435-40. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12533248&dopt=Abstract
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The expression of matrix metalloproteinase-1 mRNA induced by ultraviolet A1 (340400 nm) is phototherapy relevant to the glutathione (GSH) content in skin fibroblasts of systemic sclerosis. Author(s): Yin L, Yamauchi R, Tsuji T, Krutmann J, Morita A. Source: The Journal of Dermatology. 2003 March; 30(3): 173-80. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12692352&dopt=Abstract
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The glutathione system in alkylator resistance. Author(s): Hamilton D, Fotouhi-Ardakani N, Batist G. Source: Cancer Treat Res. 2002; 112: 67-87. Review. No Abstract Available. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12481712&dopt=Abstract
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The interaction of sodium chlorite with phospholipids and glutathione: a comparison of effects in vitro, in mammalian and in microbial cells. Author(s): Ingram PR, Homer NZ, Smith RA, Pitt AR, Wilson CG, Olejnik O, Spickett CM. Source: Archives of Biochemistry and Biophysics. 2003 February 1; 410(1): 121-33. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12559984&dopt=Abstract
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The levels of serum vitamin C, malonyldialdehyde and erythrocyte reduced glutathione in chronic obstructive pulmonary disease and in healthy smokers. Author(s): Calikoglu M, Unlu A, Tamer L, Ercan B, Bugdayci R, Atik U. Source: Clinical Chemistry and Laboratory Medicine : Cclm / Fescc. 2002 October; 40(10): 1028-31. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12476943&dopt=Abstract
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The null genotype of glutathione s-transferase M1 and T1 locus increases the risk for thyroid cancer. Author(s): Morari EC, Leite JL, Granja F, da Assumpcao LV, Ward LS. Source: Cancer Epidemiology, Biomarkers & Prevention : a Publication of the American Association for Cancer Research, Cosponsored by the American Society of Preventive Oncology. 2002 November; 11(11): 1485-8. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12433731&dopt=Abstract
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The plasma and placental levels of malondialdehyde, glutathione and superoxide dismutase in pre-eclampsia. Author(s): Madazli R, Benian A, Aydin S, Uzun H, Tolun N. Source: Journal of Obstetrics and Gynaecology : the Journal of the Institute of Obstetrics and Gynaecology. 2002 September; 22(5): 477-80. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12521411&dopt=Abstract
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The role of an evolutionarily conserved cis-proline in the thioredoxin-like domain of human class Alpha glutathione transferase A1-1. Author(s): Nathaniel C, Wallace LA, Burke J, Dirr HW. Source: The Biochemical Journal. 2003 May 15; 372(Pt 1): 241-6. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12573033&dopt=Abstract
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The role of N-acetyltransferase-2 and glutathione S-transferase on the risk and aggressiveness of bladder cancer. Author(s): Giannakopoulos X, Charalabopoulos K, Baltogiannis D, Chatzikiriakidou A, Alamanos Y, Georgiou I, Evangelou A, Agnantis N, Sofikitis N. Source: Anticancer Res. 2002 November-December; 22(6B): 3801-4. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12552997&dopt=Abstract
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The role of various Bcl-2 domains in the anti-proliferative effect and modulation of cellular glutathione levels: a prominent role for the BH4 domain. Author(s): Hoetelmans RW, Vahrmeijer AL, van Vlierberghe RL, Keijzer R, van de Velde CJ, Mulder GJ, Van Dierendonck JH. Source: Cell Proliferation. 2003 February; 36(1): 35-44. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12558659&dopt=Abstract
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Tocotrienols inhibit human glutathione S-transferase P1-1. Author(s): van Haaften RI, Haenen GR, Evelo CT, Bast A. Source: Iubmb Life. 2002 August; 54(2): 81-4. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12440523&dopt=Abstract
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Towards more efficient glutathione peroxidase mimics: substrate recognition and catalytic group assembly. Author(s): Luo GM, Ren XJ, Liu JQ, Mu Y, Shen JC. Source: Current Medicinal Chemistry. 2003 July; 10(13): 1151-83. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12678808&dopt=Abstract
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Transport of glutathione conjugates and chemotherapeutic drugs by RLIP76 (RALBP1): a novel link between G-protein and tyrosine kinase signaling and drug resistance. Author(s): Awasthi S, Singhal SS, Sharma R, Zimniak P, Awasthi YC. Source: International Journal of Cancer. Journal International Du Cancer. 2003 September 20; 106(5): 635-46. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12866021&dopt=Abstract
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Upregulation of glutathione-related genes and enzyme activities in cultured human cells by sublethal concentrations of inorganic arsenic. Author(s): Schuliga M, Chouchane S, Snow ET. Source: Toxicological Sciences : an Official Journal of the Society of Toxicology. 2002 December; 70(2): 183-92. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12441363&dopt=Abstract
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Up-regulation of interferon-gamma production by reduced glutathione, anthocyane and L-cysteine treatment in children with allergic asthma and recurrent respiratory diseases. Author(s): Chernyshov VP, Omelchenko LI, Treusch G, Vodyanik MA, Pochinok TV, Gumenyuk ME, Zelinsky GM. Source: Russ J Immunol. 2002 April; 7(1): 48-56. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12687266&dopt=Abstract
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Use of heterologously-expressed cytochrome P450 and glutathione transferase enzymes in toxicity assays. Author(s): Guengerich FP, Wheeler JB, Chun YJ, Kim D, Shimada T, Aryal P, Oda Y, Gillam EM. Source: Toxicology. 2002 December 27; 181-182: 261-4. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12505322&dopt=Abstract
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Vitamin C augments lymphocyte glutathione in subjects with ascorbate deficiency. Author(s): Lenton KJ, Sane AT, Therriault H, Cantin AM, Payette H, Wagner JR. Source: The American Journal of Clinical Nutrition. 2003 January; 77(1): 189-95. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12499341&dopt=Abstract
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VP1 pseudocapsids, but not a glutathione-S-transferase VP1 fusion protein, prevent polyomavirus infection in a T-cell immune deficient experimental mouse model. Author(s): Vlastos A, Andreasson K, Tegerstedt K, Hollanderova D, Heidari S, Forstova J, Ramqvist T, Dalianis T. Source: Journal of Medical Virology. 2003 June; 70(2): 293-300. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12696121&dopt=Abstract
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Zinc treatment prevents lipid peroxidation and increases glutathione availability in Wilson's disease. Author(s): Farinati F, Cardin R, D'inca R, Naccarato R, Sturniolo GC. Source: The Journal of Laboratory and Clinical Medicine. 2003 June; 141(6): 372-7. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12819634&dopt=Abstract
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CHAPTER 2. NUTRITION AND GLUTATHIONE Overview In this chapter, we will show you how to find studies dedicated specifically to nutrition and glutathione.
Finding Nutrition Studies on Glutathione 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 “glutathione” (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.
122 Glutathione
The following is a typical result when searching for recently indexed consumer information on glutathione: •
New aspects of glutathione biochemistry and transport - selective alteration of glutathione metabolism. Source: Meister, Alton Nutrition-reviews (USA). (December 1984). volume 42(12) page 397-410.
Additional consumer oriented references include: •
A semisynthetic glutathione peroxidase with high catalytic efficiency. Selenoglutathione transferase. Author(s): Key Laboratory for Supramolecular Structure and Materials of Ministry of Education, Jilin University, Changchun, China Source: Ren, X Jemth, P Board, P G Luo, G Mannervik, B Liu, J Zhang, K Shen, J ChemBiol. 2002 July; 9(7): 789-94 1074-5521
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Analysis of phospholipid hydroperoxide glutathione peroxidase mRNA. Author(s): Department of Animal Science, Cornell University, Ithaca, NY, USA. Source: Lei, X G Cheng, W H Methods-Mol-Biol. 2002; 196: 183-93 1064-3745
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Cathepsin B responsiveness to glutathione and lipoic acid redox. Author(s): Department of Pharmacology and Toxicology, Wright State University, School of Medicine, Dayton, OH 45435, USA.
[email protected] Source: Lockwood, T D Antioxid-Redox-Signal. 2002 August; 4(4): 681-91 1523-0864
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Chromate sensitivity in fission yeast is caused by increased glutathione reductase activity and peroxide overproduction. Author(s): Department of General and Environmental Microbiology, University of Pecs, Hungary.
[email protected] Source: Pesti, M Gazdag, Z Emri, T Farkas, N Koosz, Z Belagyi, J Pocsi, I J-BasicMicrobiol. 2002; 42(6): 408-19 0233-111X
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Differential modulation of growth and glutathione metabolism in cultured rat astrocytes by 4-hydroxynonenal and green tea polyphenol, epigallocatechin-3-gallate. Author(s): Department of Anatomy, Faculty of Medicine and Health Sciences, UAE University, Al Ain, United Arab Emirates. Source: Ahmed, I John, A Vijayasarathy, C Robin, M A Raza, H Neurotoxicology. 2002 September; 23(3): 289-300 0161-813X
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Dual role of glutathione in modulating camptothecin activity: depletion potentiates activity, but conjugation enhances the stability of the topoisomerase I-DNA cleavage complex. Author(s): Department of Medicine, Duke Comprehensive Cancer Center, Duke University Medical Center, Durham, North Carolina 27710, USA. Source: Gamcsik, M P Kasibhatla, M S Adams, D J Flowers, J L Colvin, O M ManikuMarch, G Wani, M Wall, M E Kohlhagen, G Pommier, Y Mol-Cancer-Ther. 2001 November; 1(1): 11-20 1535-7163
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Effects of a vitamin E-bonded membrane and of glutathione on anemia and erythropoietin requirements in hemodialysis patients. Author(s): Nephrology and Dialysis Service, Manerbio Hospital, Brescia, Italy.
[email protected]
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Source: Usberti, M Gerardi, G Micheli, A Tira, P Bufano, G Gaggia, P Movilli, E Cancarini, G C De Marinis, S D'Avolio, G Broccoli, R Manganoni, A Albertin, A Di Lorenzo, D J-Nephrol. 2002 Sep-October; 15(5): 558-64 1120-3625 •
Expression of glutathione transferase isoenzymes in the human H295R adrenal cell line and the effect of forskolin. Author(s): Wallenberg Laboratory, Unit for Biochemical Toxicology, Department of Biochemistry and Biophysics, Stockholm University, S-10691 Stockholm, Sweden.
[email protected] Source: Stark, T Mankowitz, L DePierre, J W J-Biochem-Mol-Toxicol. 2002; 16(4): 169-73 1095-6670
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Feasibility and correlates of arsenic trioxide combined with ascorbic acid-mediated depletion of intracellular glutathione for the treatment of relapsed/refractory multiple myeloma. Author(s): Sylvester Comprehensive Cancer Center, University of Miami, Florida, USA. Source: Bahlis, N J McCafferty Grad, J Jordan McMurry, I Neil, J Reis, I Kharfan Dabaja, M Eckman, J Goodman, M Fernandez, H F Boise, L H Lee, K P Clin-Cancer-Res. 2002 December; 8(12): 3658-68 1078-0432
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Genomic cloning and characterization of glutathione reductase gene from Brassica campestris var. Pekinensis. Author(s): Department of Animal Science and Biotechnology, Kyungpook National University, Daegu, Korea. Source: Lee, H Won, S H Lee, B H Park, H D Chung, W I Jo, J Mol-Cells. 2002 April 30; 13(2): 245-51 1016-8478
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Glutathione-dependent system of antioxidant defense in the placenta in preterm delivery. Author(s): D. O. Ott Institute of Obstetrics and Gynecology, Russian Academy of Medical Sciences, St. Petersburg. Source: Prokopenko, V M Partsalis, G K Pavlova, N G Burmistrov, S O Arutyunyan, A V Bull-Exp-Biol-Med. 2002 May; 133(5): 442-3 0007-4888
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Lead stimulates the glutathione system in selective regions of rat brain. Author(s): Laboratory of Pathobiochemistry of the Central Nervous System, Department of Neurochemistry, Medical Research Centre, Polish Academy of Sciences, Warszawa, Poland.
[email protected] Source: Struzynska, L Sulkowski, G Lenkiewicz, A Rafalowska, U Folia-Neuropathol. 2002; 40(4): 203-9
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Lipoic acid and vitamin C potentiate nitric oxide synthesis in human aortic endothelial cells independently of cellular glutathione status. Author(s): Linus Pauling Institute, Oregon State University, Corvallis, Oregon, USA.
[email protected] Source: Visioli, F Smith, A Zhang, W Keaney, J F Jr Hagen, T Frei, B Redox-Repage 2002; 7(4): 223-7 1351-0002
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Mercury toxicity and antioxidants: Part 1: role of glutathione and alpha-lipoic acid in the treatment of mercury toxicity. Source: Patrick, L Altern-Med-Revolume 2002 December; 7(6): 456-71 1089-5159
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Pentylenetetrazol-induced seizures and kindling: changes in free fatty acids, superoxide dismutase, and glutathione peroxidase activity. Author(s): Department of Pharmacology, Medical School, University of Rijeka, Rijeka, Croatia.
[email protected]
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Source: Erakovic, V Zupan, G Varljen, J Simonic, A Neurochem-Int. 2003 January; 42(2): 173-8 0197-0186 •
Targeting the mitochondria: an exciting new approach to myeloma therapy. Commentary re: N. J. Bahlis et al., Feasibility and correlates of arsenic trioxide combined with ascorbic acid-mediated depletion of intracellular glutathione for the treatment of relapsed/refractory multiple myeloma. Clin. Cancer Res., 8: 3658-3668, 2002. Author(s): H. Lee Moffitt Cancer Center and Research Institute, Tampa, Florida 33612, USA. Source: Dalton, W S Clin-Cancer-Res. 2002 December; 8(12): 3643-5 1078-0432
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The effects of dietary sulfur amino acid deficiency on rat brain glutathione concentration and neural damage in global hemispheric hypoxia-ischemia. Author(s): College of Pharmacy and Nutrition, University of Saskatchewan, 110 Science Place, Saskatoon, Sask., S7N 5C9, Canada. Source: Bobyn, P J Franklin, J L Wall, C M Thornhill, J A Juurlink, B H Paterson, P G Nutr-Neurosci. 2002 December; 5(6): 407-16 1028-415X
The following information is typical of that found when using the “Full IBIDS Database” to search for “glutathione” (or a synonym): •
A semisynthetic glutathione peroxidase with high catalytic efficiency. Selenoglutathione transferase. Author(s): Key Laboratory for Supramolecular Structure and Materials of Ministry of Education, Jilin University, Changchun, China Source: Ren, X Jemth, P Board, P G Luo, G Mannervik, B Liu, J Zhang, K Shen, J ChemBiol. 2002 July; 9(7): 789-94 1074-5521
•
Analysis of phospholipid hydroperoxide glutathione peroxidase mRNA. Author(s): Department of Animal Science, Cornell University, Ithaca, NY, USA. Source: Lei, X G Cheng, W H Methods-Mol-Biol. 2002; 196: 183-93 1064-3745
•
Cathepsin B responsiveness to glutathione and lipoic acid redox. Author(s): Department of Pharmacology and Toxicology, Wright State University, School of Medicine, Dayton, OH 45435, USA.
[email protected] Source: Lockwood, T D Antioxid-Redox-Signal. 2002 August; 4(4): 681-91 1523-0864
•
Chromate sensitivity in fission yeast is caused by increased glutathione reductase activity and peroxide overproduction. Author(s): Department of General and Environmental Microbiology, University of Pecs, Hungary.
[email protected] Source: Pesti, M Gazdag, Z Emri, T Farkas, N Koosz, Z Belagyi, J Pocsi, I J-BasicMicrobiol. 2002; 42(6): 408-19 0233-111X
•
Differential modulation of growth and glutathione metabolism in cultured rat astrocytes by 4-hydroxynonenal and green tea polyphenol, epigallocatechin-3-gallate. Author(s): Department of Anatomy, Faculty of Medicine and Health Sciences, UAE University, Al Ain, United Arab Emirates. Source: Ahmed, I John, A Vijayasarathy, C Robin, M A Raza, H Neurotoxicology. 2002 September; 23(3): 289-300 0161-813X
•
Dual role of glutathione in modulating camptothecin activity: depletion potentiates activity, but conjugation enhances the stability of the topoisomerase I-DNA cleavage complex. Author(s): Department of Medicine, Duke Comprehensive Cancer Center, Duke University Medical Center, Durham, North Carolina 27710, USA.
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Source: Gamcsik, M P Kasibhatla, M S Adams, D J Flowers, J L Colvin, O M ManikuMarch, G Wani, M Wall, M E Kohlhagen, G Pommier, Y Mol-Cancer-Ther. 2001 November; 1(1): 11-20 1535-7163 •
Effects of a vitamin E-bonded membrane and of glutathione on anemia and erythropoietin requirements in hemodialysis patients. Author(s): Nephrology and Dialysis Service, Manerbio Hospital, Brescia, Italy.
[email protected] Source: Usberti, M Gerardi, G Micheli, A Tira, P Bufano, G Gaggia, P Movilli, E Cancarini, G C De Marinis, S D'Avolio, G Broccoli, R Manganoni, A Albertin, A Di Lorenzo, D J-Nephrol. 2002 Sep-October; 15(5): 558-64 1120-3625
•
Expression of glutathione transferase isoenzymes in the human H295R adrenal cell line and the effect of forskolin. Author(s): Wallenberg Laboratory, Unit for Biochemical Toxicology, Department of Biochemistry and Biophysics, Stockholm University, S-10691 Stockholm, Sweden.
[email protected] Source: Stark, T Mankowitz, L DePierre, J W J-Biochem-Mol-Toxicol. 2002; 16(4): 169-73 1095-6670
•
Feasibility and correlates of arsenic trioxide combined with ascorbic acid-mediated depletion of intracellular glutathione for the treatment of relapsed/refractory multiple myeloma. Author(s): Sylvester Comprehensive Cancer Center, University of Miami, Florida, USA. Source: Bahlis, N J McCafferty Grad, J Jordan McMurry, I Neil, J Reis, I Kharfan Dabaja, M Eckman, J Goodman, M Fernandez, H F Boise, L H Lee, K P Clin-Cancer-Res. 2002 December; 8(12): 3658-68 1078-0432
•
Genomic cloning and characterization of glutathione reductase gene from Brassica campestris var. Pekinensis. Author(s): Department of Animal Science and Biotechnology, Kyungpook National University, Daegu, Korea. Source: Lee, H Won, S H Lee, B H Park, H D Chung, W I Jo, J Mol-Cells. 2002 April 30; 13(2): 245-51 1016-8478
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Glutathione-dependent system of antioxidant defense in the placenta in preterm delivery. Author(s): D. O. Ott Institute of Obstetrics and Gynecology, Russian Academy of Medical Sciences, St. Petersburg. Source: Prokopenko, V M Partsalis, G K Pavlova, N G Burmistrov, S O Arutyunyan, A V Bull-Exp-Biol-Med. 2002 May; 133(5): 442-3 0007-4888
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Lead stimulates the glutathione system in selective regions of rat brain. Author(s): Laboratory of Pathobiochemistry of the Central Nervous System, Department of Neurochemistry, Medical Research Centre, Polish Academy of Sciences, Warszawa, Poland.
[email protected] Source: Struzynska, L Sulkowski, G Lenkiewicz, A Rafalowska, U Folia-Neuropathol. 2002; 40(4): 203-9
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Lipoic acid and vitamin C potentiate nitric oxide synthesis in human aortic endothelial cells independently of cellular glutathione status. Author(s): Linus Pauling Institute, Oregon State University, Corvallis, Oregon, USA.
[email protected] Source: Visioli, F Smith, A Zhang, W Keaney, J F Jr Hagen, T Frei, B Redox-Repage 2002; 7(4): 223-7 1351-0002
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Mercury toxicity and antioxidants: Part 1: role of glutathione and alpha-lipoic acid in the treatment of mercury toxicity. Source: Patrick, L Altern-Med-Revolume 2002 December; 7(6): 456-71 1089-5159
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Pentylenetetrazol-induced seizures and kindling: changes in free fatty acids, superoxide dismutase, and glutathione peroxidase activity. Author(s): Department of Pharmacology, Medical School, University of Rijeka, Rijeka, Croatia.
[email protected] Source: Erakovic, V Zupan, G Varljen, J Simonic, A Neurochem-Int. 2003 January; 42(2): 173-8 0197-0186
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Targeting the mitochondria: an exciting new approach to myeloma therapy. Commentary re: N. J. Bahlis et al., Feasibility and correlates of arsenic trioxide combined with ascorbic acid-mediated depletion of intracellular glutathione for the treatment of relapsed/refractory multiple myeloma. Clin. Cancer Res., 8: 3658-3668, 2002. Author(s): H. Lee Moffitt Cancer Center and Research Institute, Tampa, Florida 33612, USA. Source: Dalton, W S Clin-Cancer-Res. 2002 December; 8(12): 3643-5 1078-0432
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The effects of dietary sulfur amino acid deficiency on rat brain glutathione concentration and neural damage in global hemispheric hypoxia-ischemia. Author(s): College of Pharmacy and Nutrition, University of Saskatchewan, 110 Science Place, Saskatoon, Sask., S7N 5C9, Canada. Source: Bobyn, P J Franklin, J L Wall, C M Thornhill, J A Juurlink, B H Paterson, P G Nutr-Neurosci. 2002 December; 5(6): 407-16 1028-415X
Federal Resources on Nutrition In addition to the IBIDS, the United States Department of Health and Human Services (HHS) and the United States Department of Agriculture (USDA) provide many sources of information on general nutrition and health. Recommended resources include: •
healthfinder®, HHS’s gateway to health information, including diet and nutrition: http://www.healthfinder.gov/scripts/SearchContext.asp?topic=238&page=0
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The United States Department of Agriculture’s Web site dedicated to nutrition information: www.nutrition.gov
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The Food and Drug Administration’s Web site for federal food safety information: www.foodsafety.gov
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The National Action Plan on Overweight and Obesity sponsored by the United States Surgeon General: http://www.surgeongeneral.gov/topics/obesity/
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The Center for Food Safety and Applied Nutrition has an Internet site sponsored by the Food and Drug Administration and the Department of Health and Human Services: http://vm.cfsan.fda.gov/
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Center for Nutrition Policy and Promotion sponsored by the United States Department of Agriculture: http://www.usda.gov/cnpp/
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Food and Nutrition Information Center, National Agricultural Library sponsored by the United States Department of Agriculture: http://www.nal.usda.gov/fnic/
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Food and Nutrition Service sponsored by the United States Department of Agriculture: http://www.fns.usda.gov/fns/
Additional Web Resources A number of additional Web sites offer encyclopedic information covering food and nutrition. The following is a representative sample: •
AOL: http://search.aol.com/cat.adp?id=174&layer=&from=subcats
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Family Village: http://www.familyvillage.wisc.edu/med_nutrition.html
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Google: http://directory.google.com/Top/Health/Nutrition/
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Healthnotes: http://www.healthnotes.com/
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Open Directory Project: http://dmoz.org/Health/Nutrition/
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Yahoo.com: http://dir.yahoo.com/Health/Nutrition/
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WebMDHealth: http://my.webmd.com/nutrition
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WholeHealthMD.com: http://www.wholehealthmd.com/reflib/0,1529,00.html
The following is a specific Web list relating to glutathione; please note that any particular subject below may indicate either a therapeutic use, or a contraindication (potential danger), and does not reflect an official recommendation: •
Vitamins Vitamin B2 Source: Healthnotes, Inc.; www.healthnotes.com
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Minerals Cisplatin Source: Healthnotes, Inc.; www.healthnotes.com Selenium Source: Healthnotes, Inc.; www.healthnotes.com Selenium Source: Integrative Medicine Communications; www.drkoop.com Selenium Source: Prima Communications, Inc.www.personalhealthzone.com Sulfur Source: Integrative Medicine Communications; www.drkoop.com
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Food and Diet Asparagus Source: WholeHealthMD.com, LLC.; www.wholehealthmd.com Hyperlink: http://www.wholehealthmd.com/refshelf/foods_view/0,1523,7,00.html Avocados Source: WholeHealthMD.com, LLC.; www.wholehealthmd.com Hyperlink: http://www.wholehealthmd.com/refshelf/foods_view/0,1523,46,00.html
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CHAPTER 3. ALTERNATIVE MEDICINE AND GLUTATHIONE Overview In this chapter, we will begin by introducing you to official information sources on complementary and alternative medicine (CAM) relating to glutathione. 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 glutathione 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 “glutathione” (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 glutathione: •
Are kavalactones the hepatotoxic principle of kava extracts? The pitfalls of the glutathione theory. Author(s): Schmidt M. Source: Journal of Alternative and Complementary Medicine (New York, N.Y.). 2003 April; 9(2): 183-7; Author Reply 187-8. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12804070&dopt=Abstract
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Beta-carotene supplementation decreases leukocyte superoxide dismutase activity and serum glutathione peroxidase concentration in humans( small star, filled ). Author(s): McGill CR, Green NR, Meadows MC, Gropper SS. Source: The Journal of Nutritional Biochemistry. 2003 November; 14(11): 656-62. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=14629897&dopt=Abstract
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Bioflavonoid stimulation of glutathione transport by the 190-kDa multidrug resistance protein 1 (MRP1). Author(s): Leslie EM, Deeley RG, Cole SP. Source: Drug Metabolism and Disposition: the Biological Fate of Chemicals. 2003 January; 31(1): 11-5. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12485947&dopt=Abstract
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Cloning, characterization and regulation of a family of phi class glutathione transferases from wheat. Author(s): Cummins I, O'Hagan D, Jablonkai I, Cole DJ, Hehn A, Werck-Reichhart D, Edwards R. Source: Plant Molecular Biology. 2003 June; 52(3): 591-603. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12956529&dopt=Abstract
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Covalent binding to glutathione of the DNA-alkylating antitumor agent, S23906-1. Author(s): David-Cordonnier MH, Laine W, Joubert A, Tardy C, Goossens JF, Kouach M, Briand G, Thi Mai HD, Michel S, Tillequin F, Koch M, Leonce S, Pierre A, Bailly C. Source: European Journal of Biochemistry / Febs. 2003 July; 270(13): 2848-59. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12823555&dopt=Abstract
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Critical role of allyl groups and disulfide chain in induction of Pi class glutathione transferase in mouse tissues in vivo by diallyl disulfide, a naturally occurring chemopreventive agent in garlic. Author(s): Bose C, Guo J, Zimniak L, Srivastava SK, Singh SP, Zimniak P, Singh SV. Source: Carcinogenesis. 2002 October; 23(10): 1661-5. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12376475&dopt=Abstract
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Cypermethrin induces glutathione S-transferase activity in the shore crab, Carcinus maenas. Author(s): Gowlan BT, Moffat CF, Stagg RM, Houlihan DF, Davies IM. Source: Marine Environmental Research. 2002 August; 54(2): 169-77. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12206409&dopt=Abstract
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Cypermethrin-induced plasma membrane perturbation on erythrocytes from rats: reduction of fluidity in the hydrophobic core and in glutathione peroxidase activity. Author(s): Gabbianelli R, Falcioni G, Nasuti C, Cantalamessa F. Source: Toxicology. 2002 June 14; 175(1-3): 91-101. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12049839&dopt=Abstract
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Cysteine supplementation improves the erythrocyte glutathione synthesis rate in children with severe edematous malnutrition. Author(s): Badaloo A, Reid M, Forrester T, Heird WC, Jahoor F.
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Source: The American Journal of Clinical Nutrition. 2002 September; 76(3): 646-52. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12198013&dopt=Abstract •
Dietary glutathione protects rats from diabetic nephropathy and neuropathy. Author(s): Ueno Y, Kizaki M, Nakagiri R, Kamiya T, Sumi H, Osawa T. Source: The Journal of Nutrition. 2002 May; 132(5): 897-900. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11983810&dopt=Abstract
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Differential modulation of growth and glutathione metabolism in cultured rat astrocytes by 4-hydroxynonenal and green tea polyphenol, epigallocatechin-3-gallate. Author(s): Ahmed I, John A, Vijayasarathy C, Robin MA, Raza H. Source: Neurotoxicology. 2002 September; 23(3): 289-300. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12387357&dopt=Abstract
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Dual role of glutathione in modulating camptothecin activity: depletion potentiates activity, but conjugation enhances the stability of the topoisomerase I-DNA cleavage complex. Author(s): Gamcsik MP, Kasibhatla MS, Adams DJ, Flowers JL, Colvin OM, Manikumar G, Wani M, Wall ME, Kohlhagen G, Pommier Y. Source: Molecular Cancer Therapeutics. 2001 November; 1(1): 11-20. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12467234&dopt=Abstract
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Effect of CDA-II on cell viability, lipid peroxidation, glutathione concentration and its related enzyme activities in primary rat hepatocytes. Author(s): Lin WC, Liao YC, Liau MC, Sheen LY. Source: The American Journal of Chinese Medicine. 2003; 31(3): 415-23. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12943172&dopt=Abstract
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Effect of glutathione on oxymyoglobin oxidation. Author(s): Tang J, Faustman C, Lee S, Hoagland TA. Source: Journal of Agricultural and Food Chemistry. 2003 March 12; 51(6): 1691-5. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12617606&dopt=Abstract
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Effect of reduced glutathione on the stability of pigments in paprika powders studied by multiwavelength spectrometry and high-performance liquid chromatography. Author(s): Cserhati T, Forgacs E, Darwish Y, Morais H, Mota T, Ramos AC. Source: J Chromatogr A. 2002 March 8; 949(1-2): 269-73. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11999743&dopt=Abstract
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Effect of S-(1,2-dicarboxyethyl) glutathione and S-(1,2-dicarboxyethyl) cysteine on the stimulus-induced superoxide generation and tyrosyl phosphorylation of proteins in human neutrophils. Author(s): Wang C, Lu H, Chen G, Yamashita K, Manabe M, Kodama H.
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Source: Clinical Chemistry and Laboratory Medicine : Cclm / Fescc. 2002 November; 40(11): 1101-4. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12521225&dopt=Abstract •
Effect of vitamin C supplementation on reduced glutathione and malondialdehyde in patients with acute myocardial infarction. Author(s): Miglani A, Seth RK, Siwach SB. Source: Clinica Chimica Acta; International Journal of Clinical Chemistry. 2003 January; 327(1-2): 187-8. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12482635&dopt=Abstract
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Effects of extract of Ginkgo biloba leaves and its constituents on carcinogenmetabolizing enzyme activities and glutathione levels in mouse liver. Author(s): Sasaki K, Hatta S, Wada K, Ueda N, Yoshimura T, Endo T, Sakata M, Tanaka T, Haga M. Source: Life Sciences. 2002 February 22; 70(14): 1657-67. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11991253&dopt=Abstract
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Effects of Ginkgo biloba extract and tanshinone on cytochrome P-450 isozymes and glutathione transferase in rats. Author(s): Yang XF, Wang NP, Lu WH, Zeng FD. Source: Acta Pharmacologica Sinica. 2003 October; 24(10): 1033-8. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=14531948&dopt=Abstract
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Effects of oral N-acetylcysteine on plasma homocysteine and whole blood glutathione levels in healthy, non-pregnant women. Author(s): Roes EM, Raijmakers MT, Peters WH, Steegers EA. Source: Clinical Chemistry and Laboratory Medicine : Cclm / Fescc. 2002 May; 40(5): 496-8. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12113295&dopt=Abstract
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Effects of zinc deficiency and supplementation on malondialdehyde and glutathione levels in blood and tissues of rats performing swimming exercise. Author(s): Ozturk A, Baltaci AK, Mogulkoc R, Oztekin E, Sivrikaya A, Kurtoglu E, Kul A. Source: Biological Trace Element Research. 2003 August; 94(2): 157-66. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12958407&dopt=Abstract
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Environmental cadmium levels increase phytochelatin and glutathione in lettuce grown in a chelator-buffered nutrient solution. Author(s): Maier EA, Matthews RD, McDowell JA, Walden RR, Ahner BA.
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Source: J Environ Qual. 2003 July-August; 32(4): 1356-64. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12931891&dopt=Abstract •
Genistein, a soy isoflavone, induces glutathione peroxidase in the human prostate cancer cell lines LNCaP and PC-3. Author(s): Suzuki K, Koike H, Matsui H, Ono Y, Hasumi M, Nakazato H, Okugi H, Sekine Y, Oki K, Ito K, Yamamoto T, Fukabori Y, Kurokawa K, Yamanaka H. Source: International Journal of Cancer. Journal International Du Cancer. 2002 June 20; 99(6): 846-52. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12115487&dopt=Abstract
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Glutathione ester but not glutathione protects against cisplatin-induced ototoxicity in a rat model. Author(s): Campbell KC, Larsen DL, Meech RP, Rybak LP, Hughes LF. Source: Journal of the American Academy of Audiology. 2003 April; 14(3): 124-33. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12859137&dopt=Abstract
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Glutathione in kwashiorkor. Author(s): Jackson AA. Source: The American Journal of Clinical Nutrition. 2002 September; 76(3): 495-6. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12197988&dopt=Abstract
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Glutathione S-transferases and malondialdehyde in the liver of NOD mice on shortterm treatment with plant mixture extract P-9801091. Author(s): Petlevski R, Hadzija M, Slijepcevic M, Juretic D, Petrik J. Source: Phytotherapy Research : Ptr. 2003 April; 17(4): 311-4. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12722130&dopt=Abstract
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Impact of oral L-glutamine on glutathione, glutamine, and glutamate blood levels in volunteers. Author(s): Valencia E, Marin A, Hardy G. Source: Nutrition (Burbank, Los Angeles County, Calif.). 2002 May; 18(5): 367-70. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11985937&dopt=Abstract
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Influence of ginger rhizome (Zingiber officinale Rosc) on survival, glutathione and lipid peroxidation in mice after whole-body exposure to gamma radiation. Author(s): Jagetia GC, Baliga MS, Venkatesh P, Ulloor JN. Source: Radiation Research. 2003 November; 160(5): 584-92. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=14565823&dopt=Abstract
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Insecticides in Chinese medicinal plants: survey leading to jacaranone, a neurotoxicant and glutathione-reactive quinol. Author(s): Xu H, Zhang N, Casida JE.
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Source: Journal of Agricultural and Food Chemistry. 2003 April 23; 51(9): 2544-7. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12696934&dopt=Abstract •
Mercury toxicity and antioxidants: Part 1: role of glutathione and alpha-lipoic acid in the treatment of mercury toxicity. Author(s): Patrick L. Source: Alternative Medicine Review : a Journal of Clinical Therapeutic. 2002 December; 7(6): 456-71. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12495372&dopt=Abstract
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Modulation of age-related biochemical changes and oxidative stress by vitamin C and glutathione supplementation in old rats. Author(s): Amer MA. Source: Annals of Nutrition & Metabolism. 2002; 46(5): 165-8. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12378038&dopt=Abstract
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Phenotyping of human glutathione S-transferase hGSTT1-1: a comparison of two ex vivo routine procedures. Author(s): Muller M, Bunger J, Voss M, Westphal G, Ruhnau P, Hallier E. Source: Archives of Toxicology. 2002 November; 76(11): 634-42. Epub 2002 August 09. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12415426&dopt=Abstract
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Platinum/paclitaxel-based chemotherapy in advanced ovarian carcinoma: glutathione S-transferase genetic polymorphisms as predictive biomarkers of disease outcome. Author(s): Medeiros R, Pereira D, Afonso N, Palmeira C, Faleiro C, Afonso-Lopes C, Freitas-Silva M, Vasconcelos A, Costa S, Osorio T, Lopes C. Source: International Journal of Clinical Oncology / Japan Society of Clinical Oncology. 2003 June; 8(3): 156-61. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12851839&dopt=Abstract
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Protection of insulin-secreting INS-1 cells against oxidative stress through adenoviral-mediated glutathione peroxidase overexpression. Author(s): Moriscot C, Richard MJ, Favrot MC, Benhamou PY. Source: Diabetes & Metabolism. 2003 April; 29(2 Pt 1): 145-51. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12746635&dopt=Abstract
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Relative activities of organosulfur compounds derived from onions and garlic in increasing tissue activities of quinone reductase and glutathione transferase in rat tissues. Author(s): Munday R, Munday CM. Source: Nutrition and Cancer. 2001; 40(2): 205-10. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11962257&dopt=Abstract
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Sanguinarine-induced apoptosis is associated with an early and severe cellular glutathione depletion. Author(s): Debiton E, Madelmont JC, Legault J, Barthomeuf C. Source: Cancer Chemotherapy and Pharmacology. 2003 June; 51(6): 474-82. Epub 2003 April 17. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12700925&dopt=Abstract
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Selective expression of glutathione S-transferase genes in the murine gastrointestinal tract in response to dietary organosulfur compounds. Author(s): Andorfer JH, Tchaikovskaya T, Listowsky I. Source: Carcinogenesis. 2003 November 21 [epub Ahead of Print] http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=14633659&dopt=Abstract
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Selenium supplementation acting through the induction of thioredoxin reductase and glutathione peroxidase protects the human endothelial cell line EAhy926 from damage by lipid hydroperoxides. Author(s): Lewin MH, Arthur JR, Riemersma RA, Nicol F, Walker SW, Millar EM, Howie AF, Beckett GJ. Source: Biochimica Et Biophysica Acta. 2002 December 16; 1593(1): 85-92. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12431787&dopt=Abstract
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Significance of nuclear glutathione S-transferase pi in resistance to anti-cancer drugs. Author(s): Goto S, Kamada K, Soh Y, Ihara Y, Kondo T. Source: Japanese Journal of Cancer Research : Gann. 2002 September; 93(9): 1047-56. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12359059&dopt=Abstract
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Synergistic versus antagonistic actions of glutamate and glutathione: the role of excitotoxicity and oxidative stress in neuronal disease. Author(s): Shaw CA, Bains JS. Source: Cell Mol Biol (Noisy-Le-Grand). 2002 March; 48(2): 127-36. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11990449&dopt=Abstract
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Transport of glutathione conjugates and chemotherapeutic drugs by RLIP76 (RALBP1): a novel link between G-protein and tyrosine kinase signaling and drug resistance. Author(s): Awasthi S, Singhal SS, Sharma R, Zimniak P, Awasthi YC. Source: International Journal of Cancer. Journal International Du Cancer. 2003 September 20; 106(5): 635-46. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12866021&dopt=Abstract
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Additional Web Resources A number of additional Web sites offer encyclopedic information covering CAM and related topics. The following is a representative sample: •
Alternative Medicine Foundation, Inc.: http://www.herbmed.org/
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AOL: http://search.aol.com/cat.adp?id=169&layer=&from=subcats
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Chinese Medicine: http://www.newcenturynutrition.com/
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drkoop.com: http://www.drkoop.com/InteractiveMedicine/IndexC.html
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Family Village: http://www.familyvillage.wisc.edu/med_altn.htm
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Google: http://directory.google.com/Top/Health/Alternative/
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Healthnotes: http://www.healthnotes.com/
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MedWebPlus: http://medwebplus.com/subject/Alternative_and_Complementary_Medicine
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Open Directory Project: http://dmoz.org/Health/Alternative/
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HealthGate: http://www.tnp.com/
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WebMDHealth: http://my.webmd.com/drugs_and_herbs
•
WholeHealthMD.com: http://www.wholehealthmd.com/reflib/0,1529,00.html
•
Yahoo.com: http://dir.yahoo.com/Health/Alternative_Medicine/
The following is a specific Web list relating to glutathione; 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 Alcoholism Source: Integrative Medicine Communications; www.drkoop.com Amyloidosis Source: Integrative Medicine Communications; www.drkoop.com Asthma Source: Healthnotes, Inc.; www.healthnotes.com Bone Cancer Source: Integrative Medicine Communications; www.drkoop.com Brain Cancer Source: Integrative Medicine Communications; www.drkoop.com Breast Cancer Source: Integrative Medicine Communications; www.drkoop.com
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Burns Source: Integrative Medicine Communications; www.drkoop.com Cancer Prevention (reducing the Risk) Source: Prima Communications, Inc.www.personalhealthzone.com Cataracts Source: Healthnotes, Inc.; www.healthnotes.com Cirrhosis Source: Integrative Medicine Communications; www.drkoop.com Colon Cancer Source: Healthnotes, Inc.; www.healthnotes.com Colorectal Cancer Source: Integrative Medicine Communications; www.drkoop.com Dermatitis Herpetiformis Source: Healthnotes, Inc.; www.healthnotes.com Diabetes Source: Healthnotes, Inc.; www.healthnotes.com Diabetes Source: Prima Communications, Inc.www.personalhealthzone.com Gastritis Source: Integrative Medicine Communications; www.drkoop.com HIV and AIDS Support Source: Healthnotes, Inc.; www.healthnotes.com Insulin Resistance Syndrome Source: Healthnotes, Inc.; www.healthnotes.com Liver Cirrhosis Source: Healthnotes, Inc.; www.healthnotes.com Liver Disease Source: Integrative Medicine Communications; www.drkoop.com Lung Cancer Source: Integrative Medicine Communications; www.drkoop.com Lymphoma Source: Integrative Medicine Communications; www.drkoop.com Miscarriage Source: Integrative Medicine Communications; www.drkoop.com
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Osteoarthritis Source: Prima Communications, Inc.www.personalhealthzone.com Pancreatic Insufficiency Source: Healthnotes, Inc.; www.healthnotes.com Parkinson's Disease Source: Integrative Medicine Communications; www.drkoop.com Peptic Ulcer Source: Integrative Medicine Communications; www.drkoop.com Radiation Damage Source: Integrative Medicine Communications; www.drkoop.com Rheumatoid Arthritis Source: Integrative Medicine Communications; www.drkoop.com Spontaneous Abortion Source: Integrative Medicine Communications; www.drkoop.com Stomach Inflammation Source: Integrative Medicine Communications; www.drkoop.com Viral Hepatitis Source: Prima Communications, Inc.www.personalhealthzone.com •
Herbs and Supplements Acetaminophen Source: Healthnotes, Inc.; www.healthnotes.com Aesculus Alternative names: Horse Chestnut; Aesculus hippocastanum L. Source: Alternative Medicine Foundation, Inc.; www.amfoundation.org Aloe Alternative names: Aloe vera L. Source: Alternative Medicine Foundation, Inc.; www.amfoundation.org Alpha Lipoic Acid Source: Healthnotes, Inc.; www.healthnotes.com Amino Acids Source: WholeHealthMD.com, LLC.; www.wholehealthmd.com Hyperlink: http://www.wholehealthmd.com/refshelf/substances_view/0,1525,10003,00.html Antioxidants Source: WholeHealthMD.com, LLC.; www.wholehealthmd.com Hyperlink: http://www.wholehealthmd.com/refshelf/substances_view/0,1525,10004,00.html
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Antioxidants and Free Radicals Source: Healthnotes, Inc.; www.healthnotes.com Arctium Alternative names: Burdock, Gobo; Arctium lappa L. Source: Alternative Medicine Foundation, Inc.; www.amfoundation.org Arnica Alternative names: Arnica montana L. Source: Alternative Medicine Foundation, Inc.; www.amfoundation.org Boswellia Alternative names: Frankincense; Boswellia serrata Roxb. Source: Alternative Medicine Foundation, Inc.; www.amfoundation.org Chemotherapy Source: Healthnotes, Inc.; www.healthnotes.com Cinnamomum Alternative names: Cinnamon; Cinnamomum zeylanicum Source: Alternative Medicine Foundation, Inc.; www.amfoundation.org Coenzyme Q10 Source: Integrative Medicine Communications; www.drkoop.com Coq10 Source: Integrative Medicine Communications; www.drkoop.com Curcuma Alternative names: Turmeric; Curcuma longa L. Source: Alternative Medicine Foundation, Inc.; www.amfoundation.org Curcuma Longa Source: Integrative Medicine Communications; www.drkoop.com Cyclophosphamide Source: Healthnotes, Inc.; www.healthnotes.com Cyclosporine Source: Healthnotes, Inc.; www.healthnotes.com Cysteine Source: Healthnotes, Inc.; www.healthnotes.com Cysteine Source: Integrative Medicine Communications; www.drkoop.com Docetaxel Source: Healthnotes, Inc.; www.healthnotes.com
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Eugenia Clove Alternative names: Cloves; Eugenia sp. Source: Alternative Medicine Foundation, Inc.; www.amfoundation.org Fluorouracil Source: Healthnotes, Inc.; www.healthnotes.com Ginkgo Biloba Source: Integrative Medicine Communications; www.drkoop.com Glucosamine Source: Prima Communications, Inc.www.personalhealthzone.com Glutamine Source: Healthnotes, Inc.; www.healthnotes.com Glutamine Source: Integrative Medicine Communications; www.drkoop.com Glutamine Source: WholeHealthMD.com, LLC.; www.wholehealthmd.com Hyperlink: http://www.wholehealthmd.com/refshelf/substances_view/0,1525,10030,00.html Glutathione Source: Healthnotes, Inc.; www.healthnotes.com Glutathione Source: WholeHealthMD.com, LLC.; www.wholehealthmd.com Hyperlink: http://www.wholehealthmd.com/refshelf/substances_view/0,1525,854,00.html Glycyrrhiza1 Alternative names: Licorice; Glycyrrhiza glabra L. Source: Alternative Medicine Foundation, Inc.; www.amfoundation.org Indole-3-carbinol Source: Healthnotes, Inc.; www.healthnotes.com Interferon Source: Healthnotes, Inc.; www.healthnotes.com Lipotropic Combination Source: WholeHealthMD.com, LLC.; www.wholehealthmd.com Hyperlink: http://www.wholehealthmd.com/refshelf/substances_view/0,1525,861,00.html Maidenhair Tree Source: Integrative Medicine Communications; www.drkoop.com Melatonin Source: Healthnotes, Inc.; www.healthnotes.com
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Mentha Alternative names: Pennyroyal; Mentha/Hedeoma pulegium Source: Alternative Medicine Foundation, Inc.; www.amfoundation.org Methotrexate Source: Healthnotes, Inc.; www.healthnotes.com Milk Thistle Alternative names: Silybum marianum, St. Mary's Thistle Source: Integrative Medicine Communications; www.drkoop.com Milk Thistle Source: WholeHealthMD.com, LLC.; www.wholehealthmd.com Hyperlink: http://www.wholehealthmd.com/refshelf/substances_view/0,1525,10044,00.html Momordica Alternative names: Bitter Gourd, Karela; Momordica charantia Linn. Source: Alternative Medicine Foundation, Inc.; www.amfoundation.org NAC (N-Acetylcysteine) Source: WholeHealthMD.com, LLC.; www.wholehealthmd.com Hyperlink: http://www.wholehealthmd.com/refshelf/substances_view/0,1525,809,00.html N-Acetyl Cysteine Source: Healthnotes, Inc.; www.healthnotes.com N-Acetyl Cysteine (NAC) Source: Prima Communications, Inc.www.personalhealthzone.com Paclitaxel Source: Healthnotes, Inc.; www.healthnotes.com Panax Alternative names: Ginseng; Panax ginseng Source: Alternative Medicine Foundation, Inc.; www.amfoundation.org Piper Nigrum Alternative names: Black Pepper Source: Alternative Medicine Foundation, Inc.; www.amfoundation.org Ribes Alternative names: Black Currant; Ribes nigrum L. Source: Alternative Medicine Foundation, Inc.; www.amfoundation.org Rosmarinus Alternative names: Rosemary; Rosmarinus officinalis L. Source: Alternative Medicine Foundation, Inc.; www.amfoundation.org
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S-Adenosylmethionine (SAMe) Source: Integrative Medicine Communications; www.drkoop.com SAMe (S-Adenosylmethionine) Source: WholeHealthMD.com, LLC.; www.wholehealthmd.com Hyperlink: http://www.wholehealthmd.com/refshelf/substances_view/0,1525,818,00.html Sassafras Alternative names: Sassafras albidum (Nuttall) Source: Alternative Medicine Foundation, Inc.; www.amfoundation.org Schisandra Alternative names: Schisandra chinensis Source: Healthnotes, Inc.; www.healthnotes.com Silybum Alternative names: Milk Thistle; Silybum marianum (L.) Gaertn. Source: Alternative Medicine Foundation, Inc.; www.amfoundation.org Silybum Marianum Source: Integrative Medicine Communications; www.drkoop.com St. Mary's Thistle Source: Integrative Medicine Communications; www.drkoop.com Symphytum Alternative names: Comfrey; Symphytum officinale L. Source: Alternative Medicine Foundation, Inc.; www.amfoundation.org Tanacetum Alternative names: Feverfew; Tanacetum parthenium (L.) Schultz-Bip. Source: Alternative Medicine Foundation, Inc.; www.amfoundation.org Trigonella Alternative names: Fenugreek; Trigonella foenum graecum L. Source: Alternative Medicine Foundation, Inc.; www.amfoundation.org Turmeric Alternative names: Curcuma longa Source: Integrative Medicine Communications; www.drkoop.com Withania Ashwagandha Alternative names: Ashwagandha; Withania somnifera L. Source: Alternative Medicine Foundation, Inc.; www.amfoundation.org Zingiber Alternative names: Ginger; Zingiber officinale Roscoe Source: Alternative Medicine Foundation, Inc.; www.amfoundation.org
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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 GLUTATHIONE Overview In this chapter, we will give you a bibliography on recent dissertations relating to glutathione. 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 “glutathione” (or a synonym) in their titles. To accurately reflect the results that you might find while conducting research on glutathione, we have not necessarily excluded nonmedical dissertations in this bibliography.
Dissertations on Glutathione 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 glutathione. You will see that the information provided includes the dissertation’s title, its author, and the institution with which the author is associated. The following covers recent dissertations found when using this search procedure: •
A Study of the Osterberg-sarkar-kruck Method for Evaluating Free Ion Concentrations in Solutions of Complex Equilibria and a Study of the Complexation Chemistry of Glutathione by This Method by Guevremont, Roger; PhD from University of Alberta (Canada), 1978 http://wwwlib.umi.com/dissertations/fullcit/NK36391
•
Alpha-class Glutathione Transferases As Steroid Isomerases and Scaffolds for Protein Redesign by Pettersson, Par Lennart; PhD from Uppsala Universitet (Sweden), 2002, 38 pages http://wwwlib.umi.com/dissertations/fullcit/f409249
•
An Enzyme-based Dechlorination of Pcbs: Glutathione-s-transferase from the Northern Quahog, Mercinaria Mercinaria, As a Promising Candidate by Blanchette, Brian N.; PhD from University of Massachusetts Lowell, 2002, 173 pages http://wwwlib.umi.com/dissertations/fullcit/3036399
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•
An Esr Spin Trapping Study on the Role of Free Radicals, Glutathione and Vitamin E in 3-methylindole-induced Lung Disease by Kubow, Stanley Jan; PhD from University of Guelph (Canada), 1985 http://wwwlib.umi.com/dissertations/fullcit/NK65604
•
Ascorbate-glutathione Cycle Responses during Cucumber Fruit Chilling Stress by French, David Andrew; PhD from The University of Wisconsin - Madison, 2003, 270 pages http://wwwlib.umi.com/dissertations/fullcit/3089705
•
Cloning, Expression and Characterization of a Unique Human Liver Microsomal Glutathione-s-transferase by Liken, Andrew David; PhD from the Pennsylvania State University, 2002, 107 pages http://wwwlib.umi.com/dissertations/fullcit/3051693
•
Dietary Supplementation of N-acetylcysteine to Protein Malnourished Mice Normalizes Immune Response: Role of Glutathione Levels, Redox Status and Nfkappab Activation by Li, Jun; PhD from the Ohio State University, 2002, 105 pages http://wwwlib.umi.com/dissertations/fullcit/3049070
•
Enzymology at the Dimer Interface of Cytosolic Glutathione S-transferases by Lyon, Robert Patrick; PhD from University of Washington, 2002, 156 pages http://wwwlib.umi.com/dissertations/fullcit/3072112
•
Exploration of Escherichia Coli As a Selection System for the Directed Evolution of House Fly (musca Domestica) Glutathione S-transferase-3 Specificity for Phosphotriester Substrates by Ericksen, Bryan Christian; PhD from University of California, Davis, 2002, 168 pages http://wwwlib.umi.com/dissertations/fullcit/3074562
•
Exploring the Functional Plasticity of Human Glutathione Transferases: Allelic Variants, Novel Isoenzyme and Enzyme Redesign by Johansson, Ann-Sofie; PhD from Uppsala Universitet (Sweden), 2002, 56 pages http://wwwlib.umi.com/dissertations/fullcit/f409233
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Expression of Glutathione-s-transferase A4-4 in Human Colon Tissues with Colitis and in Cultured Human Enterocytes (caco-2) by Ortegon Forero, Hernan; MSC from University of Guelph (Canada), 2002, 106 pages http://wwwlib.umi.com/dissertations/fullcit/MQ71209
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Glutathione Antioxidant Enzymes in Animal Models That Mimic Diabetic Retinopathy by Ketcham, Tonya Gaynell; PhD from Indiana University, 2002, 153 pages http://wwwlib.umi.com/dissertations/fullcit/3076050
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Glutathione S-transferase As a Biomarker of Heavy Metal Exposure in a Neotropical Fish Community by Jahan-Tigh, Richard Reza; MS from University of Houston-Clear Lake, 2002, 80 pages http://wwwlib.umi.com/dissertations/fullcit/1410040
•
Glutathione S-transferase Pi Regulation in Hepatocellular Carcinoma by Bakker, Jila; PhD from The Johns Hopkins University, 2003, 177 pages http://wwwlib.umi.com/dissertations/fullcit/3068115
•
Glutathione S-transferases of Rat Kidney by Jaeger, Valerie A; PhD from McGill University (Canada), 1979 http://wwwlib.umi.com/dissertations/fullcit/NK42946
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•
Glutathione-dependent Prodrugs of 6-mercaptopurine and 6-thioguanine: Characterizaton and Evaluation As Potential Chemotherapeutic Agents by Gunnarsdottir, Sjofn; PhD from the University of Wisconsin - Madison, 2002, 256 pages http://wwwlib.umi.com/dissertations/fullcit/3072868
•
Glycation As a Post-translational Modification of Myosin Structure and Function; Role of Glutathione; Glycation and Aging by Ramamurthy, Bhagavathi; PhD from the Pennsylvania State University, 2002, 88 pages http://wwwlib.umi.com/dissertations/fullcit/3077593
•
Hepatic Glutathione Content and Gamma-glutamyl Transferase Activity Acute and Chronic Effects of Ethanol by Speisky, Hernan; PhD from University of Toronto (Canada), 1986 http://wwwlib.umi.com/dissertations/fullcit/NL34218
•
In Vivo and in Vitro Hepatotoxicity and Glutathione Interactions of Nmethyldithiocarbamate, N,n-dimethyldithiocarbamate and Hydrogen Sulfide Anion in the Rat by Thompson, Rodney Wayne; PhD from Vanderbilt University, 2002, 98 pages http://wwwlib.umi.com/dissertations/fullcit/3071968
•
Molecular and Computational Approaches to Dna Evolution Applied to the Mammalian Class Mu Glutathione Transferase Gene Cluster by Huang, Mingqian; PhD from University of Virginia, 2003, 191 pages http://wwwlib.umi.com/dissertations/fullcit/3062138
•
Multiple Functions of Glutathione Transferases: a Study of Enzymatic Function, Regulatory Role and Distribution in Mouse and Man by Edalat, Maryam; PhD from Uppsala Universitet (Sweden), 2002, 36 pages http://wwwlib.umi.com/dissertations/fullcit/f409265
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Pharmacogenetic Approach to Glutathione-dependent Modification of Chemical Mutagens by Deleve, Laurie Donna; PhD from University of Toronto (Canada), 1988 http://wwwlib.umi.com/dissertations/fullcit/NL46421
•
Physiological Role of Mgsta4-4, a Glutathione S-transferase Metabolizing 4hydroxynonenal: Generation and Analysis of Mgsta4 Knockout Mouse by Engle, Mark Ryan; PhD from University of Arkansas for Medical Sciences, 2003, 166 pages http://wwwlib.umi.com/dissertations/fullcit/3088597
•
Regional Myocardial Ischemia Reperfusion Injury in Vivo: the Role of Glutathione by Leichtweis, Steven Boyd; PhD from University of Illinois at Urbana-Champaign, 2002, 201 pages http://wwwlib.umi.com/dissertations/fullcit/3070364
•
Regulation of Glutathione S-transferase B in Rat Liver by Hales, Barbara F; PhD from McGill University (Canada), 1976 http://wwwlib.umi.com/dissertations/fullcit/NK33298
•
Role of Glutathione in Hepatic Transport of Xenobiotics by Lee, Thomas Keywon; PhD from The University of Rochester, 2002, 144 pages http://wwwlib.umi.com/dissertations/fullcit/3064818
•
Roles for Oxidative Stress and the Glutathione System in a Model for Parkinson's Disease by Ehrhart, Juliann; PhD from Rutgers the State U. of N.J. - New Brunswick and U.M.D.N.J., 2003, 164 pages http://wwwlib.umi.com/dissertations/fullcit/3076811
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•
Signaling Pathways in the Transcriptional and Post-translational Regulation of the Human Glutathione S-transferase P1 Gene by Lo, Hui-wen; PhD from The Univ. of Texas H.S.C. at Houston Grad. Sch. of Biomed. Sci., 2002, 146 pages http://wwwlib.umi.com/dissertations/fullcit/3046059
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Studies on the Regulation of Plasma Glutathione Peroxidase by Bierl, Charlene Marie; PhD from Boston University, 2003, 159 pages http://wwwlib.umi.com/dissertations/fullcit/3067182
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The Functional Role of Phe-10 and the Anomalous Tyr-9 Pk(a) in Glutathione Stransferase A1-1 by Ibarra, Catherine Alejandro; PhD from University of Washington, 2002, 139 pages http://wwwlib.umi.com/dissertations/fullcit/3062953
•
The Induction of Amyloid Precursor Protein (APP) and Alpha-synuclein by Diethyldithiocarbamate (DDC) in Rat Hippocampal Astrocytes with or without Glutathione (GSH) by Cheng, Shu-Yuan; PhD from St. John's University (New York), School of Pharmacy, 2003, 95 pages http://wwwlib.umi.com/dissertations/fullcit/3082783
•
The Influence of Alcohol on Acetaminophen Hepatotoxicity: Cyp2e1 Induction and Selective Mitochondrial Glutathione Depletion by Zhao, Ping; PhD from University of Washington, 2002, 126 pages http://wwwlib.umi.com/dissertations/fullcit/3072162
•
The Role of Glutathione Peroxidases during Infection with Coxsackievirus B3 by Matthews, Colette Cynthia; PhD from the University of North Carolina at Chapel Hill, 2002, 178 pages http://wwwlib.umi.com/dissertations/fullcit/3047036
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The Role of Plant Glutathione S-transferases during Infection by Colletotrichum Destructivum and C. Orbiculare by Dean, John Douglas; MSC from University of Guelph (Canada), 2003, 156 pages http://wwwlib.umi.com/dissertations/fullcit/MQ76058
•
The Role of the Glutathione S Transfersases An9 and Bz2 and the Multidrugresistance Associated Protein Zmmrp1 in Anthocyanin Sequestration by Goodman, Christopher Dean; PhD from Stanford University, 2003, 215 pages http://wwwlib.umi.com/dissertations/fullcit/3085183
Keeping Current Ask the medical librarian at your library if it has full and unlimited access to the ProQuest Digital Dissertations database. From the library, you should be able to do more complete searches via http://wwwlib.umi.com/dissertations.
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CHAPTER 5. PATENTS ON GLUTATHIONE Overview Patents can be physical innovations (e.g. chemicals, pharmaceuticals, medical equipment) or processes (e.g. treatments or diagnostic procedures). The United States Patent and Trademark Office defines a patent as a grant of a property right to the inventor, issued by the Patent and Trademark Office.8 Patents, therefore, are intellectual property. For the United States, the term of a new patent is 20 years from the date when the patent application was filed. If the inventor wishes to receive economic benefits, it is likely that the invention will become commercially available within 20 years of the initial filing. It is important to understand, therefore, that an inventor’s patent does not indicate that a product or service is or will be commercially available. The patent implies only that the inventor has “the right to exclude others from making, using, offering for sale, or selling” the invention in the United States. While this relates to U.S. patents, similar rules govern foreign patents. In this chapter, we show you how to locate information on patents and their inventors. If you find a patent that is particularly interesting to you, contact the inventor or the assignee for further information. IMPORTANT NOTE: When following the search strategy described below, you may discover non-medical patents that use the generic term “glutathione” (or a synonym) in their titles. To accurately reflect the results that you might find while conducting research on glutathione, we have not necessarily excluded nonmedical patents in this bibliography.
Patents on Glutathione By performing a patent search focusing on glutathione, you can obtain information such as the title of the invention, the names of the inventor(s), the assignee(s) or the company that owns or controls the patent, a short abstract that summarizes the patent, and a few excerpts from the description of the patent. The abstract of a patent tends to be more technical in nature, while the description is often written for the public. Full patent descriptions contain much more information than is presented here (e.g. claims, references, figures, diagrams, etc.). We will tell you how to obtain this information later in the chapter. The following is an 8Adapted
from the United States Patent and Trademark Office: http://www.uspto.gov/web/offices/pac/doc/general/whatis.htm.
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example of the type of information that you can expect to obtain from a patent search on glutathione: •
Anti-cancer products for treating cystic fibrosis Inventor(s): Annereau; Jean-Philippe (Paris, FR), Barthe; Joel (Paris, FR), Blanquet; Sylvain (Paris, FR), Lallemand; Jean-Yves (Palaiseau, FR), Lenoir; Gerard (Paris, FR), Stoven; Veronique (Paris, FR) Assignee(s): Centre National de la Recherche Scientifique (CNRS) (Paris, FR) Patent Number: 6,635,627 Date filed: November 29, 1999 Abstract: The invention concerns a novel approach for treating cystic fibrosis using, in particular, anti-cancer chemotherapy. For the treatment of cystic fibrosis it proposes the use of at least one product which when administered to a patient brings about the expression or overexpression of an ABC carrier compound, in particular glutathione carrier. Preferably, the products used are anti-cancer products whose administration brings about the expression of MRP and/or MDR protein. The invention is also applicable to the treatment of rheumatoid polyarthritis or asthma. More specifically, the compounds are selected among cyclophosphamide, aclarubicin, doxorubicin, daunorubicin, epirubicin, idarubicin, zorubicin, pirabucin, colchicine, videsine, vinorelbine, vincristine, binblasine, azithromycin, erythromycin, ifosmamide, N-acetyl cysteine, N-acetyl lysine and/or a CFTR protein fragment comprising the NBF1 domain. Excerpt(s): This Application is a 371 of PCT/FR98/01074 filed May 28, 1998, which claims priority from France 97/06667 filed May 30, 1997. The present invention relates to a novel approach for treating cystic fibrosis which involves chemotherapy, in particular anticancer chemotherapy. Cystic fibrosis is a genetic disease which is expressed in particular in the lungs and which is due to a defect in the gene encoding the CFTR (standing for "Cystic Fibrosis Transmembrane Conductance Regulator") protein, which is a protein which is able to participate directly or indirectly in the transport of chloride ions across the cell membranes. Web site: http://www.delphion.com/details?pn=US06635627__
•
Antioxidants to neutralize tobacco free radicals Inventor(s): Hersh; Rebecca (Atlanta, GA), Hersh; Theodore (Atlanta, GA) Assignee(s): Thione International, Inc. (Atlanta, GA) Patent Number: 6,415,798 Date filed: June 30, 2000 Abstract: A composition for inclusion within a cigarette, cigar, pipe or smokeless tobacco. The composition can be included within the tobacco itself, a filter for filtering tobacco smoke once burned within the paper or wrapper surrounding the tabacco product. In the cigarette filter, be it internal or external filters, the antioxidant complex is capable of scavenging and neutralizing the free radicals emanating from the burning or heated tobacco and passing through the filter as the smoker inhales. The composition is also capable of reducing free radical damage to the oro-pharyngeal cavity, respiratory tract and lungs resulting from tobacco smoke. The composition includes glutathione
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and preferaby L-glutathione and sources of the antioxidant enzymes catalase and superoxide dismutase. Excerpt(s): The present invention deals with the combination of various synergistic antioxidants, enzymatic co-factors and amino acids in appropriate delivery vehicles employed in cigarette filters and in external filters such as cigarette and cigar "holders," in "pipe filters" and in tobacco, wrappers and papers and in so-called smokeless tobacco as a means of preventing or ameliorating signs and symptoms and complications to the oro-pharyngeal cavity, respiratory tract and lungs from damage by tobacco smoke and tobacco chewed induced free radical species. The present invention can be employed in filter cigarettes, unfiltered cigarettes, cigars, pipes, and smokeless tobacco products. The deleterious effects of tobacco abuse are well known and regulatory agencies as well as the public constantly react to these scientific and epidemiologic evidences. Tobacco is indeed a worldwide public health hazard accounting for significant morbidity and mortality. Although smoking places an abundant oxidant insult to the oral cavity, respiratory tract and lungs, evidence supports the notion that the oxidant burden is on the entire organism of the smoker. Smoking promotes development or enhancement of atherosclerosis, causing cardiovascular disease, chronic obstructive pulmonary disease, recently labeled "smoker's lung," cutaneous damage, especially to the face, called "smoker's face," and various forms of cancer, including carcinomas of the mouth, pharynx, esophagus and lung. Tobacco is a substance consisting of the dried leaves and stems of the plant Nicotiana tabacum. Tobacco contains the drug nicotine, which is very addictive. The plant is native to North America and now is grown worldwide. Tobacco abuse has been identified as the single most preventable cause of disease, morbidity and mortality, for tobacco smoke contains many toxic chemicals, in tar and gas phase smoke. Web site: http://www.delphion.com/details?pn=US06415798__ •
Combination and method of treatment of cancer utilizing a COX-2 inhibitor and a 3hydroxy-3-methylglutaryl-coenzyme-a (HMG-CoA) reductase inhibitor Inventor(s): Guilford; F. Timothy (829 Forest Ave., Palo Alto, CA 94301), Kindness; George (7207 Stonebrook Ct., Middletown, OH 45044), Schumm, III; Brooke (2813 Thornbrook Rd., Ellicott City, MD 21042) Assignee(s): none reported Patent Number: 6,534,540 Date filed: July 25, 2001 Abstract: The inventors propose a combination of an HMG-CoA reductase inhibitor (also referred to as "HMG-CoA inhibitor(s)"), and COX-2 inhibitor for the treatment of cancer especially prostate cancer and a method of treatment of cancer by that combination, especially prostate cancer. The inventors propose a combination of an HMG-CoA reductase inhibitor, COX-2 inhibitor, and glutathione pathway enhancing and detoxifying compound, particularly cystine, for the treatment of cancer especially prostate cancer and a method of treatment of cancer by that combination, especially prostate cancer. Based on the clinical results of retardation, but not cure of cancer, the combination has the characteristic of sufficiently interfering with replication and apparently restoring the immune system capacity to manage cancer. Excerpt(s): Traditional cancer treatments have generally used an approach which is focused on directly attacking cells with a propensity to divide. The cancer cell is viewed as a bad cell that must be eliminated. The methods and combinations chosen focus on
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destruction of the dividing cell, or chemical attack of the cell. This invention proposes a different methodology. The first premise is to recognize the highly adaptable characteristics and durable biochemistry of the cancer cell from a biochemical and genetic viewpoint. Many cancer cells are body cells gone awry. The literature solidly suggests that cancer cells in a patient's body have a capability to readapt their functions to adjust to ambient conditions. A patient's body also has an impressive capability to adapt to changing macro-environmental conditions, as well as the micro-environmental conditions in biological chemistry internal to the cell. Web site: http://www.delphion.com/details?pn=US06534540__ •
Composition comprising a carnitine and glutathione, useful to increase the absorption of glutathione and synergize its effects Inventor(s): Cavazza; Claudio (Rome, IT) Assignee(s): Sigma-Tau Healthscience S.p.A. (Pomezia, IT) Patent Number: 6,306,392 Date filed: December 15, 2000 Abstract: A composition useful for increasing the absorption of glutathione and for synergizing its effects. This composition may take the form of a dietary supplement, dietetic support or of an actual medicine and comprises: (a) propionyl L-carnitine or a pharmacologically acceptable salt thereof; (b) glutathione or a glutathione-containing yeast; (c) a glutathione-free yeast if the component (b) consists of glutathione. The invention is also directed to methods of making this composition as well as to methods of prevention or treatment using it. Excerpt(s): This is a 371 of PCT/IT00/00129 filed Apr. 17, 2000. The present invention relates to a composition for the prevention and/or treatment of alterations of those organs which perform the most intense metabolic function, such as the liver, kidneys, cardiovascular system and brain. More particularly, such composition is useful to treat or prevent hepatosis, nephropathies and cardiovascular or cerebral damages such as damages provoked by ageing or due to an altered metabolism of such organs or provoked by toxic substances. Web site: http://www.delphion.com/details?pn=US06306392__
•
Compositions and kits comprising alpha-adrenergic receptor antagonists and nitric oxide donors and methods of use Inventor(s): Garvey; David S. (Dover, MA), Saenz de Tejada; Inigo (Madrid, ES), Schroeder; Joseph D. (Boston, MA) Assignee(s): NitroMed, Inc. (Bedford, MA) Patent Number: 6,294,517 Date filed: September 1, 1998 Abstract: The present invention describes novel compositions and kits comprising alpha-adrenergic receptor antagonists and compounds that donate, transfer or release nitric oxide, elevate endogenous levels of endothelium-derived relaxing factor, or stimulate nitric oxide synthesis. In preferred embodiments, the alpha-adrenergic receptor antagonist is an alkaloid selected from the group consisting of rauwolscine,
Patents 153
corynanthine, yohimbine, apoyohimbine, beta-yohimbine, yohimbol, pseudoyohimbine and epi-3.alpha.-yohimbine, and the compound that donates, transfers or releases nitric oxide, elevates endogenous levels of endothelium-derived relaxing factor, or stimulates nitric oxide synthesis is selected from the group consisting of L-arginine, S-nitroso-Nacetylcysteine, S-nitroso-captopril, S-nitroso-homocysteine, S-nitroso-cysteine and Snitroso-glutathione. In other embodiments, the present invention describes novel compositions comprising yohimbine and L-arginine. In still other embodiments, the invention describes novel compositions comprising yohimbine and L-arginine where the yohimbine is derived from yohimbe bark or Rauwolfia root. The novel compositions of the invention are useful for treating impotence in males and females. Excerpt(s): This invention generally relates to nitrosated and/or nitrosylated.alpha.adrenergic receptor antagonists, compositions containing them and their use in treating sexual dysfunctions. Adequate sexual function is a complex interaction of hormonal events and psychosocial relationships. There are four stages to sexual response as described in the International Journal of Gynecology & Obstetrics, 51(3):265-277 (1995). The first stage of sexual response is desire. The second stage of sexual response is arousal. Both physical and emotional stimulation may lead to breast and genital vasodilation and clitoral engorement (vasocongestion). In the female, dilation and engorgement of the blood vessels in the labia and tissue surrounding the vagina produce the "orgasmic platform," an area at the distal third of the vagina where blood becomes sequestered. Localized perivaginal swelling and vaginal lubrication make up the changes in this stage of sexual response. Subsequently, ballooning of the proximal portion of the vagina and elevation of the uterus occurs. In the male, vasodilation of the cavernosal arteries and closure of the venous channels that drain the penis produce an erection. The third stage of sexual response is orgasm, while the fourth stage is resolution. Interruption or absence of any of the stages of the sexual response cycle can result in sexual dysfunction. One study found that 35% of males and 42% of females reported some form of sexual dysfunction. Read et al, J. Public Health Med., 19(4):387391 (1997). In both pre-menopausal and menopausal females, sexual dysfunction can include, for example, sexual pain disorders, sexual desire disorders, sexual arousal dysfunction, orgasmic dysfunction, dyspareunia, and vaginismus. Sexual dysfunction can be caused, for example, by pregnancy, menopause, cancer, pelvic surgery, chronic medical illness or medications. Web site: http://www.delphion.com/details?pn=US06294517__ •
Enhanced storage organ production in plants Inventor(s): Bowley; Stephen R (Guelph, CA), Jones; Kim S (Toronto, CA), McKersie; Bryan D (Apex, NC), Samis; Karen (Guelph, CA) Assignee(s): University of Guelph (Guelph, CA) Patent Number: 6,518,486 Date filed: June 10, 1999 Abstract: A method for increasing the mass of a storage organ of a plant comprising tansforming the plant with at least one heterologous gene that encodes an enzyme that results in NAD(P)H consumption is disclosed. Preferably the method comprises transforming the plant with a gene that encodes an enzyme that is directly involved in NAD(P)H consumption. Such plants are characterized as having an increase in the mass of the storage organs. The enzymes include but are not limited to alcohol dehydrogenase, glutathione reductase, dehydroascorbate reductase,
154 Glutathione
monodehydroascorbate reductase, mitochondrial alternative oxidase, NADH oxidase and NADPH oxidize. Vector and transformed plants are also disclosed. Excerpt(s): The invention relates to genetically transformed plants that develop larger storage organs. More specifically this invention relates to plants comprising a heterologous gene encoding an enzyme involved in NAD(P)H consumption. These plants develop larger roots, exhibit increased growth, and increased stress tolerance. Perennial crops, including many forage crops, persist in cultivated fields for several years. Because these plants are capable of multiple cycles of regrowth and harvest, the growth and development are distinctly different than annual grain crops. In most perennial forage production systems, for example alfalfa (Medicago sativa), plants are defoliated before any seed is produced and, unlike annual crops, regrow new vegetative shoots from crown or axillary buds. The energy, carbon, nitrogen and other reserves necessary to support this regrowth come from the root system and crown. The reserves in the root and crown are depleted as the new shoots develop new leaves, which capture light energy for photosynthesis. At a certain stage of development the shoot becomes self-sufficient and obtains its energy and carbon requirements from photosynthesis. At a later stage, the shoot has excess energy and carbon from photosynthesis and exports the excess to the root and crown system to support nitrogen fixation, nutrient uptake and replenishment of reserves. Replenishment of reserves continues until the plant is defoliated again by either grazing, harvesting or natural stresses, for example, freezing. Roots or other storage organs of most forage legumes convert the imported sucrose to starch, whereas forage grasses store fructans. The rate of starch or fructan accumulation in these storage organs is usually not controlled by the supply of sucrose from the leaf. Instead, sink strength is determined by the ability of the storage organ to synthesize and store starch or fructans. This is determined in turn by the number of amyloplasts (sites of starch storage) in the cell, the number of storage cells in the root, and the metabolism of the cell. Web site: http://www.delphion.com/details?pn=US06518486__ •
Fertilizer with a chelate element Inventor(s): Takeda; Iwao (4066-2 Nakaminowa, Oaza, Minowa-cho, Kamiina-gun, Nagano, 399-4601, JP), Yoshie; Kaname (1118 Tatsuno, Oaza, Tatsuno-cho, Kamiina-gun, Nagano, 399-0421, JP) Assignee(s): none reported Patent Number: 6,391,079 Date filed: August 15, 2000 Abstract: Fertilizer with a chelate element is provided which comprises 0.01 to 4 parts of a compound of a metal for forming the central metal of a chelate compound, 1 to 5 parts of an oxycarboxylic acid, 2 to 8 parts of a potassic element, 0.1 to 1 part of a nitrogenous element, and 0.01 to 2 parts of a phosphorous element by weight, indicating a pH value of 6.0 to 7.5 when mixed with water. When a living body ingests an agricultural product cultivated with the fertilizer, the chelate derives glutathione S-transferase molecular species which can catalyze the detoxicating reaction of the electrophillic compound by the S-bonded reaction of said electrophillic compound and nucleophillic reduction-type glutathione peroxidase. Excerpt(s): The present invention relates to an manure, and particularly, a fertilizer with a chelate element comprising an oxycarboxylic acid and a metal. Fertilizers are applied
Patents 155
to soil to supply nutrition to agricultural products for increasing the yield and to prevent degradation of the fertility of the soil. It is known to supply, to soil, large amounts of three major manurial components of nitrogen (N), phosphorus (P) and potassium (K) indispensable for growth of plants. Nitrogen serves to promote synthesis of protein in a plant, division and multiplication of cells, growth of the roots and sufficient upgrowth of the leaves and stems and to advance absorption and the anabolism of the nutrition. Phosphorus is effective to accelerate growth of the roots to increase the nutrition absorbing area of them and to activate the germination. In addition, it contributes to hasten maturation of plants and increase the yield of seeds and fruits. Also, phosphorus is useful to enhance generation of starch and activity of the enzymes and microorganisms, to prevent noxious insects and to improve quality of the harvest. Potassium is efficacious to synthesize carbohydrates and nitrogen compounds, to promote anabolism, growth of the roots, flowering and fruitage to adjust evaporation of the water supplied and to increase the resistance to damages by cold weather and harmful insects. In addition to three major manurial components, the fertilizer may contain calcium (Ca), magnesium (Mg), silicon (Si), manganese (Mn), zinc (Zn), copper (Cu), molybdenum (Mo), iron (Fe), and boron (B) to directly or indirectly assist the good growth of plants. Any fertilizer is required to contain larger amounts of effective components, without disadvantageous, substances so that it allows large scale production of crops through easy treatment and inexpensive process with a low hygroscopicity and caking. In recent years, upgraded agricultural products have been required at a request of consumers who require high quality of crops with good appearance in color and luster, excellent aroma and delicious taste. Also, the consumers have needed the medicinal efficacy of the agricultural products which satisfies their health desire so that the fertilizers must be ameliorated to improve quality of the agricultural products. Web site: http://www.delphion.com/details?pn=US06391079__ •
Glutathione S-transferase homolog Inventor(s): Corley; Neil C. (Mountain View, CA), Hillman; Jennifer L. (Mountain View, CA), Shah; Purvi (Sunnyvale, CA) Assignee(s): Incyte Genomics, Inc. () Patent Number: 6,368,810 Date filed: April 16, 1999 Abstract: The invention provides a human glutathione S-transferase (GSTH) and polynucleotides which identify and encode GSTH. The invention also provides expression vectors, host cells, agonists, antibodies and antagonists. The invention also provides methods for treating and preventing disorders associated with expression of GSTH. Excerpt(s): This invention relates to nucleic acid and amino acid sequences of a novel glutathione S-transferase homolog and to the use of these sequences in the diagnosis, prevention, and treatment of cancer and inflammation. The glutathione S-transferases (GST) are a ubiquitous family of enzymes with dual substrate specificities that perform important biochemical functions of xenobiotic biotransformation and detoxification, drug metabolism, and protection of tissues against peroxidative damage and subsequent inflammatory responses. The basic reaction catalyzed by these enzymes is the conjugation of an electrophile with reduced glutathione (GSH), which results in either activation or deactivation/detoxification of the chemical. The absolute
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requirement for binding reduced GSH to a wide variety of chemicals necessitates a diversity in GST structures in various organisms and cell types. In most cases, GSTs perform the beneficial function of deactivation and detoxification of potentially mutagenic and carcinogenic chemicals. However, in some cases their action is detrimental and produces mutagenic and carcinogenic effects. Some forms of rat and human GSTs are reliable preneoplastic markers that aid in the detection of carcinogenesis. Expression of human GSTs in bacterial strains, such as Salmonella tylphimurium, used in the well known Ames test for mutagenicity, has helped to establish the role of these enzymes in mutagenesis. Dihalomethanes, which produce liver rumors in mice, are believed to be activated by GST. This view is supported by the finding that dihalomethanes are more mutagenic in bacterial cells expressing human GST than in untransfected cells (Thier, R. et al. (1993) Proc. Natl. Acad. Sci. 90: 8567-80). The mutagenicity of ethylene dibromide and ethylene dichloride is increased in bacterial cells expressing the human Alpha GST, A1-1, while the mutagenicity of aflatoxin B1 is substantially reduced by enhancing the expression of GST (Simula, T.P. et al. (1993) Carcinogenesis 14: 1371-6). Thus, control of GST activity may be useful in the control of mutagenesis and carcinogenesis. Web site: http://www.delphion.com/details?pn=US06368810__ •
Immortalized human corneal epithelial cell line Inventor(s): Offord Cavin; Elizabeth (Poliez-Pittet, CH), Pfeifer; Andrea M. A. (St-Legier, CH), Sharif; Najam A. (Arlington, TX), Tromvoukis; Yvonne (Mollie-Margot, CH) Assignee(s): Nestec S.A. (Vevey, CH) Patent Number: 6,284,537 Date filed: December 23, 1997 Abstract: Immortalized human cornea). epithelial cell line capable of becoming stratified, and capable of expressing (1) metabolic markers specific for non-immortalized human epithelial cells such as vimentin, cytokeratins, connections between the cells, cytochrome P450s, a glutathione-S-transferase, Cu/Zn-superoxide dismutase, glutathione peroxidase, aldehyde reductase and catalase; (2) metabolic differentiation markers specific for non-immortalized human cornea). epithelial cells such as the cytokeratin of 64 kfl, the glutathione-stransferase hGST 5.8, and the profile of cytokines and growth factors comprising the compounds TNF.alpha., IL-1.beta., IL-1.alpha., IL-6, IL-8, GM CSF-.beta., IL-ra, TGF-.beta.1, TGF-.beta.2, TGF.alpha., EGF, PDGF-.beta.; (3) and markers specific for an inflammatory reaction such as collagenase I, the bradykinin, histamine and PAF receptors, and the system for transduction of an inflammatory signal by the phosphoinositides. Process for identifying the mutagenic, toxic or beneficial effect of an agent on the metabolism of the corneal cells, in which (1) an agent suspected of being a mutagenic, toxic or beneficial agent for the metabolism of the cells of the human cornea 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. Excerpt(s): The subject of the present invention is new immortalized human corneal epithelial cell lines as well as their use in processes for the identification of agents which are mutagenic, toxic or beneficial to the metabolism of the corneal cells. 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 which are sensitive
Patents 157
to the surroundings of the human body. The epithelial cells differ from other cells of the human body in the expression of compounds or structures which are found only in the epithelial cells, such as, for example, cytokeratins (Moll et al., Cell, 31, 11-24, 1982), connections between the cells (Gumbiner et al., Cell, 69, 385-387, 1992), and vimentin (Richard et al., Arch. Dematol. Res., 282, 512-515, 1990). Web site: http://www.delphion.com/details?pn=US06284537__ •
Immune stimulating dietary supplement and method of use thereof Inventor(s): Meydani; Mohsen (Newton, MA), Meydani; Simin Nikbin (Newton, MA) Assignee(s): Trustees of Tufts College (Medford, MA) Patent Number: 6,642,259 Date filed: March 25, 2002 Abstract: The immune system of middle aged and elderly individuals is stimulated with a dietary supplement. The dietary supplement includes Vitamin E, Vitamin B6 and conjugated linoleic acid. The dietary supplement can further include glutathione alone or in combination with Vitamin C, folic acid, zinc, selenium, Vitamin D, copper and Vitamin B12. The dietary supplement is administered to middle aged and elderly individuals in a suitable form for consumption by the individual. Suitable forms of consumption can include a snack bar, tablet, capsule, powder, drink, or dairy products. Excerpt(s): Immune responses gradually decline with increasing age. Coincident with a decline in immune responses is a concomitant increase in the incidence of tumor development, infection and inflammatory diseases in middle aged and elderly populations of individuals. ("Fundamental Immunology" ed. W.E. Paul, Raven Press, NY (1989); Miller, R. A., Exp. Gerontol. 29:21-35 (1994). Compromised nutritional status can contribute to the impaired immunological state and, hence, declining health of aging individuals. Thus, there is a need to develop convenient and effective methods that augment the nutritional requirements of middle aged and elderly individuals, thereby stimulating the immune system to combat disease. The present invention relates to a dietary supplement. It also is directed to a method to stimulate the immune system of middle aged and elderly individuals or to stimulate proliferation of a lymphocyte by administration of the dietary supplement. In one embodiment, the dietary supplement comprises Vitamin E, Vitamin B6 and conjugated linoleic acid. In a specific embodiment, the dietary supplement includes Vitamin E in an amount in a range of between about 10 milligrams and about 267 milligrams per milligram of Vitamin B6, and conjugated linoleic acid in an amount in a range of between about 17 milligrams and about 100 milligrams per milligram of Vitamin B6. In another specific embodiment, the dietary supplement further includes glutathione Vitamin C, folic acid, zinc, selenium, Vitamin D, copper, Vitamin B12 and glutathione. Preferably, the dietary supplement includes Vitamin C in an amount in a range of between about 17 milligrams and about 200 milligrams per milligram of Vitamin B6; folic acid in an amount in a range of between about 0.05 milligrams and about 0.2 milligrams per milligram of Vitamin B6; zinc in an amount in a range of between about 1.67 milligrams and about 10 milligrams per milligram of Vitamin B6; selenium in an amount in a range of between about 0.005 milligrams and about 0.02 milligrams per milligram of Vitamin B6; Vitamin D in an amount in a range of between about 0.0008 milligrams and about 0.005 milligrams per milligram of Vitamin B6; copper in an amount in a range of between about 0.00008 milligrams and about 0.0007 milligrams per milligram of Vitamin B6; Vitamin B12 in an amount in a range of between about 0.0002 milligrams and about 0.001 milligrams per
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milligram of Vitamin B6; and glutathione in an amount in a range of between about 4 milligrams and about 33 milligrams per milligram of Vitamin B6. Web site: http://www.delphion.com/details?pn=US06642259__ •
Isolated human enzyme proteins, nucleic acid molecules encoding human enzyme proteins, and uses thereof Inventor(s): Beasley; Ellen M. (Darnestown, MD), Di Francesco; Valentina (Rockville, MD), Gan; Weiniu (Gaithersburg, MD), Gong; Fangcheng (Germantown, MD) Assignee(s): Applera Corporation (Norwalk, CT) Patent Number: 6,468,774 Date filed: April 2, 2001 Abstract: The present invention provides amino acid sequences of glutathione peroxidase polypeptides that are encoded by genes within the human genome. The present invention specifically provides isolated peptide and nucleic acid molecules, methods of identifying orthologs and paralogs of the enzyme peptides, and methods of identifying modulators of the enzyme peptides. Excerpt(s): The present invention is in the field of enzyme proteins that are related to the glutathione peroxidase subfamily, recombinant DNA molecules, and protein production. The present invention specifically provides novel peptides and proteins and nucleic acid molecules encoding such peptide and protein molecules, all of which are useful in the development of human therapeutics and diagnostic compositions and methods. Many human enzymes serve as targets for the action of pharmaceutically active compounds. Several classes of human enzymes that serve as such targets include helicase, steroid esterase and sulfatase, convertase, synthase, dehydrogenase, monoxygenase, transferase, kinase, glutanase, decarboxylase, isomerase and reductase. It is therefore important in developing new pharmaceutical compounds to identify target enzyme proteins that can be put into high-throughput screening formats. The present invention advances the state of the art by providing novel human drug target enzymes related to the glutathione peroxidase subfamily. Glutathione peroxidase (EC 1.11.1.9) catalyzes the reduction of hydrogen peroxide, organic hydroperoxide, and lipid peroxides by reduced glutathione and functions in the protection of cells against oxidative damage. This enzyme, found mainly in the cytosol of mammalian cells, is unusual in its content of a selenocysteine residue in its active site that is encoded by a TGA opal codon (Chambers et al., 1986). The glutathione peroxidase found in plasma is immunologically distinct from the erythrocyte and liver cytosolic enzymes. It also has some differences in physical and kinetic properties. Takahashi et al. (1990) isolated cDNA clones coding for plasma GPX. They found that the nucleotide sequence consisted of a 678-bp open reading frame coding for a 226-amino acid polypeptide with a molecular mass of 25,389. The amino acid sequence showed only 44% homology with human cellular GPX. Northern blot analysis showed a single transcript of 2.2 kb in the polyadenylated RNA fractions of human placenta and of a human hepatic cell line, HepG2, but not in those of human liver and endothelial cells. Takahashi et al. (1990) concluded that as the plasma enzyme contains 1 atom of selenium per subunit, the inframe TGA observed at positions 217-219 could be assigned to selenocysteine. Web site: http://www.delphion.com/details?pn=US06468774__
Patents 159
•
Liver cell clones for use in extracorporeal liver-assist device Inventor(s): Kazuo; Izumi (Hiroshima, JP), Kimura; Hajime (Tokyo-To, JP), Klinkmann; Horst (Rostock, DE), Qiang; Shi (Tianjin, CN) Assignee(s): JMS Co., Ltd. (JP) Patent Number: 6,294,380 Date filed: July 29, 1999 Abstract: A blood perfusion device or apparatus that is used for bioartificial liver support. Human hepatocyte lines established from normal regenerating liver tissue and modulated in toxin-challenging conditions are provided. These functional hepatocytes exhibit extraordinarily enhanced detoxification functions, which are characterized by the elevated glutathione content and glutathione S-transferase activity. A bioreactor is constructed with the functional hepatocytes for bioartificial liver support system, which includes perfusion inlets and perfusion outlets, a containment vessel, a centrifugal pump and macroporous microcarriers where the functional hepatocytes are grown. Excerpt(s): The present invention generally relates to a liver-assist device and liver cell clones which may find application in artificial liver systems, extracorporeal liver-assist devices and bioreactors. More particularly, the present invention is directed to a liver cell clone with enhanced detoxification activities. The liver cell clone is characterized as having increased GSH content and elevated GST activity as compared to conventional immortalized human hepatocyte cell lines and primary human hepatocyte cultures isolated from liver tissue. Over the past several years, the focus of investigations employing extracorporeal liver support systems for the treatment of fulminant liver failure and liver dysfunction has been shifting from basic experimentation and animal trials to clinical evaluations and applications. Some groups in the United States are conducting, under the supervision of the Food and Drug Administration, clinical trials with various bioartificial liver devices (See, e.g., Rozga J. et al., J. Ann. Surg. 219:538-46, 1994, Sussman N. L. et al., Amer. J. Kid. Dis. 18:371-84, 1996, Sussman N. L., Clin Invest. Med. 19:393-9, 1996, Dixit V., Scan. J. Gastroenterol. Suppl. 220:101-14, 1996). Similarly, several groups in Euro-Asia (in particular, Germany, the Netherlands, Great Britain, and Russia) have commenced pre-clinical trials into the effectiveness of bioartificial-liver devices in treating liver dysfunctions (See, e.g., Gerlach J., Transplant. Proc. 29:852, 1997, Hughes R. D et al., Semin. Liver Dis. 16:435-444, 1996). Research into bioartificial liver support devices is also quite active in Japan. The immediate objective of temporary liver support (which may be provided by bioartifical-liver devices) is to maintain a patient with acute or fulminant hepatic failure or dysfunction until the patient's own liver regenerates. From the clinical data available, it appears that liver support systems are mainly used to bridge the patient to orthotopic transplantation, to improve cerebral circulation and to improve hemo-dynamic parameters. Web site: http://www.delphion.com/details?pn=US06294380__
•
Method and composition for treating malignant cells Inventor(s): Rubin; David (San Diego, CA) Assignee(s): Co-Enzyme Technology Ltd. (San Diego, CA) Patent Number: 6,407,071 Date filed: October 24, 2000
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Abstract: A composition for treating tumors comprising a combination of at least one oxidizing agent and at least one aldehyde or precursor thereof, which aldehyde forms an insoluble thiazoline with cysteine. Optionally a compound which inhibits glutathione-s-transferase is included. Excerpt(s): The present invention is directed to a method and composition for treating malignant cells. Control of cell growth is one of the most important aspects of an animal's physiology. The cells of an adult must divide frequently enough to allow tissues to remain in a steady state, and division must be stimulated at wounds or when special requirements are placed on the tissues. There must be many circulating cellspecific factors that signal individual cell types whether to divide or not. However, uninhibited cell growth results in malignant tumors. One of the greatest problems associated with treatment of cancers is delivery of a cytotoxic agent directly to the tumor or cancer cells without affecting normal cells of the body. Although it was hoped that monoclonal antibodies could be used as delivery agents for cytotoxic drugs to treat cancers and to inhibit metastasis of existing cancers, monoclonal antibodies have not lived up to their promise. One reason for this is that there is a very high density of receptors on the surface of cancer cells. Since monoclonal antibodies are relatively large compounds, it is impossible to provide sufficient amounts of monoclonal antibodies at the cell surface to effectively destroy the cells. In other words, the monoclonal antibodies are so large that only a very few can be present at the surface of a cell at any one time. Web site: http://www.delphion.com/details?pn=US06407071__ •
Method for detecting a substance having an activity to inhibit HIV infection using immunoassay and variant protein used for said method Inventor(s): Kim; Sung-Hou (Berkeley, CA), Ryu; Jae-Ryeon (Seoul, KR), Yu; Yeon Gyu (Seoul, KR) Assignee(s): Korea Institute of Science and Technology (Seoul, KR) Patent Number: 6,294,341 Date filed: March 19, 1999 Abstract: The present invention relates to a method for detecting a substance having an activity to inhibit HIV infection rapidly, economically and safely. The present invention uses the characteristics that if a function of transmembrane protein gp41 of HIV is inhibited, HIV infection is also inhibited, and therefore the function of gp41 depends on the interaction between two helical structures of gp41. The method of the present invention is to detect a substance to inhibit HIV infection by an immunoassay using the interaction between the variant protein Trx-N, which is prepared by binding the Nterminal helical domain of gp41 to Trx (thioredoxin) and the variant protein GST-C, which is prepared by binding the C-terminal helical domain of gp41 with GST-C (Glutathione S-transferase). This immunoassay can be used for automatic detection of the substance to inhibit the activity of gp41 can be carried out by the method. As a result, it is possible to investigate HIV infection-inhibiting activity of a number of previously known compounds or natural compounds, and it can attribute to the development of therapeutic agent of HIV infection. Excerpt(s): The present invention relates to a method for detecting substances having an activity to inhibit HIV infection. More particularly, the invention relates to an improved method for detecting substances having an activity to inhibit action of gp41, which is responsible for the infection of HIV, in order to develop a therapeutic agent for
Patents 161
Acquired Immune Deficiency Syndrome (AIDS). This method is quicker, more economical and safer than the prior art. The peptides derived from two helical region of the ectodomain of gp41 outside the cell strongly bind to each other to form a stable sixhelical bundle complex composed of a trimer of two interacting peptides (See, Chan et al., Cell 89, 263-273, 1997). It is presumed that the interaction of two helical domains plays a key role in the structural stability or function of the gp41 protein. Therefore, a substance that can inhibit the interaction between two helical structures of the gp41 proteins may inhibit HIV infection by inhibiting the action of gp41. Thus, the substance can be utilized as a therapeutic agent for AIDS. The substances having such inhibitory activity include, for example, peptides derived from two helical domains of gp41 (See, Wild et al., Pro. Natl. Acad. Sci. USA 91, 9770-9774, 1994). These peptides bind to one of the two helical domains to inhibit binding or interaction between the two helical structures of gp41. Consequently, they inhibit the function of gp41 and, as a result, inhibit HIV infection. Therefore, if a method that easily detects the interaction between two helical domains of gp41 is developed, such method will be able to be used to detect substances that inhibit the function of gp41 or HIV infection. Web site: http://www.delphion.com/details?pn=US06294341__ •
Method for preventing blood denaturation and blood test tool to be used therein Inventor(s): Higashino; Kouji (Kyoto, JP), Nishimura; Satoshi (Kyoto, JP) Assignee(s): Arkray, Inc. (Kyoto, JP) Patent Number: 6,379,318 Date filed: May 11, 2001 Abstract: A blood test tool with which blood in a dried state can be held without denaturation. In the blood test tool wherein a card made of filter paper is impregnated with the blood and then the blood is held in a dried state, a carboxylic acid such as citric acid is added to the part for holding blood. Thus, the carboxylic acid exerts an effect of preventing the blood in the dried state from denaturation. It is preferable to add a nonreducing sugar (sucrose, etc.), an anticoagulant (EDTA, etc.) and an antioxidant (glutathione, etc.) together with the carboxylic acid. This blood test tool can be produced by impregnating a filter paper card with a solution containing citric acid, etc. dissolved therein and then air-drying. Excerpt(s): The present invention relates to a method for preventing the denaturation of blood, particularly hemoglobin, and a blood test tool to be used therein. Hemoglobin Alc (HbAlc) in which hemoglobin (Hb) is bonded to glucose reflects the average glucose level of the body one or two months earlier. Therefore, it is widely used in physical examinations for geriatric diseases or treatment and consultation therefor. However, since it takes a long time to measure HbAlc, for example, even if the blood is collected from outpatients when they visits to hospital, the result of the examination of HbAlc is generally evaluated when the patient visits to the hospital the next time. Therefore, although the measurement value of HbAlc is an important factor for diagnosis of diabetes, actually, it has not been used effectively for treatment. To solve this problem, a blood collection card made of filter paper has been proposed ("Diabetes" Vol. 38, No. 10 (1995), JP10-104226A, etc.). The patients collect blood onto the collection card by themselves and allow the collection card to be impregnated with the collected blood, dried, and then mail the card to the hospital. In the hospital where this card is received, the part impregnated with the blood of the card is cut out or punched out (punch-out), and then blood is eluted therefrom. The eluted blood is examined for the predetermined
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items including HbAlc, etc. When the patient visits to the hospital, the treatment or diagnosis is performed based on the examination results. Web site: http://www.delphion.com/details?pn=US06379318__ •
Methods of treating chronic inflammatory diseases using carbonyl trapping agents Inventor(s): Shapiro; Howard K. (214 Price Ave., Apt. F-32, Narberth, PA 19072) Assignee(s): none reported Patent Number: 6,444,221 Date filed: October 12, 1999 Abstract: These and other objects of this invention are achieved by providing a novel method and compositions for the clinical treatment of chronic inflammatory diseases. This invention involves use of systemically administered compositions which include primary amine derivatives of benzoic acid as carbonyl trapping agents. These primary therapeutic agents act by chemically binding to and sequestering the aldehyde and/or ketone products of lipid peroxidation. Increased levels of lipid peroxidation have been repeatedly demonstrated as a part of the non-enzymatic "inflammatory cascade" process which underlies the secondary etiology of chronic inflammatory diseases. pAminobenzoic acid (or PABA) is an example of the primary therapeutic agent of the present invention. PABA has a small molecular weight, is water soluble, has a primary amine group that reacts with carbonyl-containing metabolites under physiological conditions and is tolerated by the body in relatively high dosages and for extended periods. The carbonyl sequestering agents are used in combination with at least one coagent so as to produce an additional beneficial physiological effect of an antiinflammatory nature. Such compositions are administered systemically entirely via the oral route. Co-agents of the present invention include anti-oxidants and free radical trapping compounds (e.g.,.alpha.-tocopherol), compounds having indirect anti-oxidant activity (e.g., selenium), vitamins (e.g., pyridoxine HCl), compounds which facilitate kidney drug elimination (e.g., glycine), metabolites at risk of depletion (e.g., pantothenic acid), sulfhydryl containing chemicals (e.g., methionine), compounds which facilitate glutathione activity (e.g., N-acetylcysteine), and non-absorbable polyamine co-agents (e.g., chitosan). Excerpt(s): This invention relates to the clinical treatment of chronic inflammatory disorders. For purposes of this invention, the category of chronic inflammatory disorders includes chronic gingivitis, chronic periodontitis, chronic autoimmune gastritis, ileitis, colitis, interstitial cystitis, arthritis, tendinitis, cumulative trauma disorders, systemic lupus erythematosus, autoimmune vasculitis, asbestosis, silicosis, Lyme disease, inflammatory myopathies, Duchenne muscular dystrophy, epilepsy, inflammatory neuropathies, myasthenia gravis, multiple sclerosis, inflammatory site edema, post-event acute central nervous system trauma, stroke, and myocardial infarction. Numerous prior art publications disclose that vitamin E functions physiologically as a lipid-soluble anti-oxidant free radical trapping agent. Prior art publications describe methionine as a water-soluble agent, an essential amino acid, an anti-oxidant and a free radical trapping agent. p-Aminobenzoic acid (PABA) is known as a water-soluble B vitamin, and several published studies have presented evidence to the effect that PABA functions, in part, as a weak anti-oxidant and a weak free radical trapping agent (Maksimov, O B and Rebachuk, N M, 1985, Table 2; Pryor, WA et al., 1976, pg. 201).
Patents 163
Web site: http://www.delphion.com/details?pn=US06444221__ •
Modulation of N-methyl-D-aspartate derivatives of glutathione
receptor
responses
with
S-substituted
Inventor(s): Regan; Raymond F. (Wayne, PA) Assignee(s): Thomas Jefferson University (Philadelphia, PA) Patent Number: 6,329,430 Date filed: August 18, 1999 Abstract: The present invention involves a method of treating pain, neurological diseases and neuronal injury in a mammal by utilizing compounds that interact with and modify one of the redox sites of the N-methyl-D-aspartate (NMDA) receptor in said mammal. These compounds include S-substituted derivatives of glutathione which modulate or regulate the NMDA glutamate receptor. Excerpt(s): The present invention relates generally to the field of neurology and to a method of treating pain, neurological diseases and neuronal injury and, more particularly, to the use of S-substituted derivatives of glutathione to modulate or regulate the N-methyl-D-aspartate (NMDA) glutamate receptor. Glutathione is a predominant intracellular antioxidant, and is present in CNS cells in millimolar concentrations. (Orlowski M. and Karkowski A., Glutathione metabolism and some possible functions of glutathione in the nervous system. Int Rev Neurobiol 19: 75-121, 1976). Cell turnover of this tripeptide is surprisingly rapid, due at least in part to release of its reduced form (GSH) into the extracellular space. (Yudkoff M., Pleasure D., Cregar L., Lin Z. P., Nissim I., Stem J. and Nissim I., Glutathione turnover in cultured astrocytes: studies with [.sup.15 N]glutamate. J Neurochem 55: 137-145, 1990). GSH release under resting conditions is quantitatively comparable to that of the excitatory neurotransmitters glutamate and aspartate, and is increased by neuronal depolarization via a calcium-dependent process. (Zangerle L., Cuenod M., Winterhalter K. H. and Do K. Q., Screening of thiol compounds: depolarization-induced release of glutathione and cysteine from rat brain slices. J Neurochem 59: 181-189, 1992). The role of extracellular glutathione has not been defined, and has been the subject of considerable conjecture. Until recently, it was presumed to function as an antioxidant and/or an amino acid transporter. GSH alone, without glutathione peroxidase, directly reacts with both the hydroxyl radical and aldehyde products of lipid peroxidation, and may therefore protect cell membranes and associated protein sulfhydryl groups from free radical attack. (Halliwell B. and Gutteridge J. M. C., Free Radicals in Biology and Medicine 2nd ed., pp. 30, 80, 210, Oxford University Press, 1989).gamma.-glutamyl transpeptidase is primarily located on the outer cell membrane and converts glutathione into gammaglutamyl amino acids and cysteinylglycine, which are then rapidly transported into cells. (Dringen R., Kranich O., Loschman P. A. and Hamprecht B., Use of dipeptides for the synthesis of glutathione by astroglia-rich primary cultures. J Neurochem 69: 868-74, 1997; Meister A. and Anderson M. E., Glutathione. Annu Rev Biochem 52: 711-760, 1983). Extracellular GSH may therefore serve as a safe carrier molecule for its constituent amino acids (glutamate, cysteine, and glycine), all of which are synaptically active. A growing body of experimental evidence suggests that extracellular GSH may also specifically interact with membrane receptors on neurons and glia. High affinity, saturable GSH binding sites have been demonstrated in both the rodent and human CNS. (Lanius R. A., Shaw C. A., Wagey R. and Krieger C., Characterization, distribution, and protein kinase C-mediated regulation of [.sup.35 S]glutathione binding sites in
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mouse and human spinal cord. J Neurochem 63: 155-160, 1994; Ogita K. and Yoneda Y., Temperature-dependent and -independent apparent binding activities of [.sup.3 H]glutathione in brain synaptic membranes. Brain Res 463: 37-46, 1988). Binding is enhanced by protein kinase C activation and is selectively inhibited by cysteine and Shexylglutathione but not by glutamate. The similar distribution of GSH and glutamate binding sites (Ogita K. and Yoneda Y., Temperature-dependent and -independent apparent binding activities of [.sup.3 H]glutathione in brain synaptic membranes. Brain Res 463: 37-46, 1988) suggests that GSH may act as a neuropeptide at the redox site of the NMDA receptor. GSH potentiated responses to glutamate in cells expressing recombinant NR1-NR2A receptors (Kohr G., Eckardt S., Luddens H., Monyer H. and Seeburg P. H., NMDA receptor channels: subunit-specific potentiation by reducing agents. Neuron 12: 1031-1040, 1994), and increased glutamate and NMDA-induced calcium influx in cultured cerebellar granule cells. (Janaky R., Varga V., Saransaari P. and Oja S. S., Glutathione modulates the N-methyl-D-aspartate (NMDA) receptoractivated calcium influx into cultured rat cerebellar granule cells. Neurosci Lett 156: 153157, 1993). Web site: http://www.delphion.com/details?pn=US06329430__ •
Multi-faceted method to repress reproduction of latent viruses in humans and animals Inventor(s): Van Dyke; Knox (Morgantown, WV) Assignee(s): HIV Diagnostics, Inc. (Lexington, KY) Patent Number: 6,514,955 Date filed: June 7, 1995 Abstract: Disclosed are methods for repressing reproduction of latent viruses, such as HIV, in animals by the generally concurrent administration of (1) antioxidants including a glutathione agent; and (2) an NFKB induction inhibitor. Also disclosed are pharmaceutical compositions and kits for use in repressing reproduction of latent viruses such as HIV. Excerpt(s): Acquired Immunodeficiency Syndrome (AIDS) is one of the most significant infections to appear in the last decade. This epidemic is not confined to a single segment of the population nor is its spread blocked by natural barriers or international boundaries. Millions have died in Africa and many more individuals are infected worldwide. In the United States more than 100,000 people have died and at least 1 million more are presently infected with the virus. This pandemic shows no signs of abating. It is strongly suspected that the causative agent in AIDS is an RNA retrovirus called the human immunodeficiency virus (HIV-1 or HIV-2). HIV possesses an envelope glycoprotein (gp120) that has a high affinity for the CD.sub.4 receptor on T helper cells and other target cells. These other target cells include bone marrow stem cells, macrophages, endothelial cells, glial cells, lymph node, dendritic cells, bowel enterochromaffin cells, cervical eptithlium and possibly Langerhans cells. However, it is the effects of HIV on T-helper cells that are the best known. The infectious process begins when the virus penetrates the body and enters the blood stream. Binding of HIV to CD.sub.4 target cells involves interaction of the external envelope glycoprotein molecule gp120 with the CD.sub.4 molecule, although other cell receptors may be involved. The virus next enters the target cell, or is internalized, through fusion of the viral envelope with the target cell membrane. Through this fusion, the virus loses its coat, and releases its RNA core and reverse transcriptase enzyme into the host cell
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cytoplasm. The HIV reverse transcriptase enzyme copies the RNA message producing first a single-stranded, and then a double-stranded, DNA (circular complementary DNA). This newly formed double-stranded DNA becomes incorporated into the host chromosomal DNA once it enters the host cell nucleus. This incorporated viral DNA may remain dormant or, upon activation, will produce viral messenger RNA (mRNA). The viral mRNA codes for proteins that are important in viral replication. Glycoprotein will then envelop the RNA genome resulting in the production of infectious viral particles; completed viral particles are then released to infect other cells. Web site: http://www.delphion.com/details?pn=US06514955__ •
Nutritional or therapeutic compositions Inventor(s): Crum; Albert (77 Remsen St., Brooklyn Heights, NY 11201) Assignee(s): none reported Patent Number: 6,592,908 Date filed: September 23, 2002 Abstract: Nutritional or therapeutic compositions containing glutamic acid, cystine, glycine and a selenium precursor and methods for their utilization to increase glutathione synthesis and thereby enhance the immune system are described. Excerpt(s): This invention relates to nutritional or therapeutic compositions useful for treating mammals to increase their body content of glutathione above a pretreatment level thereby to enhance the immune activity of the treated mammal. More specifically, it relates to compositions containing a selenium compound together with a glutathione precursor which is a mixture of glutamic acid, cystine and glycine. Its chemical name is glutamyl-cysteinyl-glycine. Like many other small peptides in the mammalian body, it is not synthesized by procedures involving DNA, RNA and ribosomes. Rather, it is synthesized from the amino acids available in the body by procedures utilizing enzymes and other body components such as adenosine triphosphate as an energy source. Web site: http://www.delphion.com/details?pn=US06592908__
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Organ preservative solution containing trehalose, anti-oxidant, cations and an energy source Inventor(s): Bull; David A. (1298 Chandler Dr., Salt Lake City, UT 84103), Karwande; Shreekanth V. (1028 Crestview Cir., Salt Lake City, UT 84108), Reid; Bruce C. (471 N. 1100 East, Bountiful, UT 84010), Stringham; James C. (1124 Augusta Way, Salt Lake City, UT 84108) Assignee(s): none reported Patent Number: 6,365,338 Date filed: April 27, 1999 Abstract: The present invention is organ and tissue preservation solutions that provide improved viability of an organ such as a heart or lung, or portion of the organ, for storage and transplantation. In particular, a solution contains trehalose, magnesium sulfate, calcium chloride, heparin, dextran, nitroglycerin, adenosine, L-arginine, allopurinol, reduced glutathione, db-cylic AMP and potassium phosphate.
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Excerpt(s): The present invention relates to a novel solution for preserving and maintaining organs and portions thereof, in particular heart and myocardial tissue and lung and lung tissue. Preservation of the viability of donor organs continues to be an important goal in transplantation. Typically the organ to be transplanted must be stored and shipped to the prospective recipient. The ability to prolong the cellular viability of the organ during storage and transportation is very important to the success of the transplant operation. Preservative solutions play an important role in the longevity of the organ. Prior known solutions for organ preservation include those described by Berdyaev et al., U.S. Pat. No. 5,432,053; Belzer et al., U.S. Pat. Nos. 4,798,824, 4,879,283; and 4,873,230; Taylor, U.S. Pat. No. 5,405,742; Dohi et al., U.S. Pat. No. 5,565,317; Stern et al., U.S. Pat. No. 5,370,989 and 5,552,267. Currently there is no consensus among practitioners regarding an optimal solution for heart preservation. Solutions include those classified as intracellular ([Na++]<70 mEq/L) or extracellular ([Na++].gtoreq.70 mEq/L). A recent survey showed that there were at least 167 organ preservation solutions available for heart transplantation, and that there was significant variation in solution usage observed among major U.S. regions of transplantation activity. (Demmy et al., Organ preservation solutions in heart transplantation--patterns of usage and related survival. Transplantation 63(2): 262-269 (1997)). Presently known solutions for cardiac preservation include those described by Oz et al., Novel Preservation Solution Permits 24-Hour Preservation in Rat and Baboon Cardiac Transplant Models, Circulation 88(2)L291-297 (1993) at Columbia University in New York, and Belzer and Southard in Transplantation 45:673-676 (1988), at the University of Wisconsin. Other solutions for heart preservation and cardioplegia include those disclosed in U.S. Pat. No. 5,407,793 by Del Nido at al. (Univ. Of Pittsburgh); and U.S. Pat. No. 4,938,961 by Collins et al.). Web site: http://www.delphion.com/details?pn=US06365338__ •
Pharmaceutical preparations of glutathione and methods of administration thereof Inventor(s): Demopolos; Harry B. (Scarsdale, NY), Seligman; Myron L. (Pleasantville, NY) Assignee(s): Antioxidant Pharmaceuticals Corp. (Elmsford, NY) Patent Number: 6,423,687 Date filed: March 19, 2001 Abstract: A method for the administration of glutathione orally comprising the administration of a bolus of glutathione which is pharmaceutically stabilized and encapsulated. The glutathione is administered on an empty stomach. The preferred stabilizer is ascorbic acid. Excerpt(s): The present invention relates to the field of antioxidant administration to mammals, and more particularly to the field of glutathione therapies as sole and combination therapies for mammals in need of such treatment. The ubiquitous tripeptide L-glutathione (GSH) (gamma-glutamyl-cysteinyl-glycine), is a well known biological antioxidant, and in fact is believed to be the primary intracellular antioxidant for higher organisms. When oxidized, it forms a dimer (GSSG), which may be recycled in organs having glutathione reductase. Glutathione may be transported through membranes by the sodium-dependent glutamate pump. Tanuguchi, N., et al. Eds., Glutathione Centennial, Academic Press, New York (1989), expressly incorporated herein by reference. Reduced glutathione (GSH) is, in the human adult, produced from oxidized glutathione (GSSG) primarily by the liver, and to a smaller extent, by the
Patents 167
skeletal muscle, red blood cells, and white cells. About 80% of the 8-10 grams glutathione produced daily is produced by the liver and distributed through the blood stream to the other tissues. Web site: http://www.delphion.com/details?pn=US06423687__ •
Protein expression system Inventor(s): Bolen; Joseph B. (4 Hamilton Ct., Lawrenceville, NJ 08648), Fargnoli; Joseph (367 Cafferty Rd., Tinicum, PA 18947), Spana; Carl (912B Village Dr. East, North Brunswick, NJ 08902) Assignee(s): none reported Patent Number: 6,303,369 Date filed: September 30, 1993 Abstract: An expression system for producing and isolating large quantities of protein. The system comprises an expression vector containing a first coding region which codes for glutathione-S-transferase operatively connected to a baculovirus promoter, a second coding region in-frame with the first coding region, and a restriction region downstream of the first coding region, into which the second coding region is inserted. A fusion protein encoded by the first and second coding region is produced by expression of the vector. Examples of this second coding region include Lck, LynB, Syk, Blk, Fyn, and Yes. A process for expression of the vector in a host cell such as Spodoptera frugiperda is also included. Excerpt(s): The present invention relates to processes for expression of proteins and to expression vectors and host cells used therefor. The lck gene product, p56.sup.lck, is a member of the src family of protein tyrosine kinases. Cooper, J. A. (1990) in Peptides and Protein Phosphorylation (Kemps, B. E., ed) pp. 85-113, CRC Press, Boca Raton, Fla. The lck protein is normally expressed in T lymphocytes and natural killer cells, where it likely performs a variety of functions relating to signal transduction through ligand binding to selected surface proteins. Bolen, J. A., and Veillette, A. (1989) Trends Biochem. Sci. 14, 404-407; Rudd, C. E. (1990) Immunol. Today 11, 400-406. In T-cells, p56.sup.lck forms a non-covalent complex with the CD4 and CD8a. Veillette, A., Bookman, M. A., Horak, E. M., and Bolen, J. A. (1988). For this reason, p56.sup.lck is believed to aid in mediation of signals emanating from the T-cell antigen receptor through ligation of CD4 or CD8 to non-polymorphic determinants on antigen-bearing major histocompatibility molecules. Shaw, A. S., Chalupny, J., Whitney, J. A., Hammond, C., Amrein, K. E., Kavathas, P., Sefton, B. M., and Rose, J. K., (1990) Mol. Cell. Biol. 10, 1853-1862; Doyle, C., and Strominger, J. L. (1987) Nature 330, 256-259; Norment, A. M., Salter, R. D., Parham, P., Engelhard, V. H., and Littman, D. R. (1988) Nature 336, 79-81. More recently, p56.sup.lck has been implicated as a signaling component of the high affinity interleukin-2 receptor. Hatakeyama, M., Kono, T., Kobayashi, N., Kawahara, A., Levin, S. D., Perlmutter, R. M., and Tanaguchi, T. (1991) Science 252, 1523-1528. A better understanding of the structure and regulation of p56.sup.lck and similar proteins would clearly contribute to our knowledge of early signal transduction events and a source of large quantities of purified p56.sup.lck would be useful. While early analysis of p56.sup.lck functions have been greatly facilitated by antibodies directed against this protein, immunoaffinity purification has been hampered by lack of an abundant source of enzyme. This difficulty has been addressed in part by baculovirus expression systems. Summers, M. D., and Smith, G. E. (1987). A Manual for baculovirus vectors and insect cell culture procedures, Texas A&M bulletin No. 1555,
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(College Station, Texas Agricultural Experimental Station and Texas A&M University), 10-39. Recent studies using a baculovirus expression system have reported significant purification of p56.sup.lck using conventional chromatography methodologies. Ramer S. E., Winkler, D. G., Carrera, A., Roberts, T. M., and Walsh, C. T. (1991) Proc. Natl. Acad. Sci. USA 88, 6254-6258; Watts, J. D., Wilson, G. M., Ettehadieh, E., Clark-Lewis, I., Kubanek, C., Astell, C. R., Marth, J. D., and Aebersold, R, (1991) J. Biol, Chem. 267, 901907. While this approach results in purified enzyme, multiple column enzyme purification is costly, time-consuming, and requires large amounts of starting material. Web site: http://www.delphion.com/details?pn=US06303369__ •
Reparatives for chemosurgery and laser (thermal) therapy Inventor(s): Hersh; Theodore (3201 Andrews Ct. NW., Atlanta, GA 30305) Assignee(s): none reported Patent Number: 6,630,442 Date filed: January 10, 1997 Abstract: A composition of glutathione and selenium, as a selenoamino acid or selenium yeast extract and an epidermal growth factor in a topical carrier and method of using the composition to reduce and repair skin damage, resulting from aesthetic (exfoliation and chemical peels) and surgical (laser and other therapies) procedures and other chemical and thermal burns to the cutaneous tissues. Excerpt(s): The present invention deals with the combination of several anti-oxidants, including enzymatic co-factors and thiol compounds, and various tissue and cell growth stimulating factors in appropriate delivery vehicles employed in topical carriers as a means of ameliorating complications and also concomitantly enhancing repair from free radical damage to the skin undergoing treatment with exfoliants or chemosurgery (chemical peels) and laser (thermal injury) therapy and also stimulating the growth, differentiation and maturation of epidermal cells resulting both from these aesthetic therapeutic procedures or interventions, burns and the existing complicating environmental and cellular metabolic factors, which also engender abundant free radicals in cutaneous tissues. When cutaneous tissues are exposed to radiation, such as solar ultraviolet rays (UVA and UVB radiation), burns from chemical and thermal injuries, damage to the skin ensues, particularly exposure to UVB which results in sunburn and tanning., Many common pathologic factors exist as the various layers of skin are injured from local release of free radical species, emanating from cellular metabolism and enhanced by the putative inflammatory injury. Skin peeling programs (chemical or thermal peels) are designed to remove "dead" skin with the aim of being replaced by new, clearer and younger cells yielding smooth and firmer skin. These treatments are recommended for solar (ultraviolet radiation) damaged skin, scarring resulting from skin conditions such as acne or for embarrassing cutaneous large pores, fine lines or the so-called "razor bumps." Home treatments (exfoliation with enzymes or alpha hydroxy acids) have been designed to bring about the separation and removal of dead skin, particularly from the face and neck without causing bleeding or scabbing or breakage of deeper dermal tissues. To avoid uneven skin results, these exfoliating chemical treatments need be applied evenly, unlike the uneven solar damage to the skin. These home peel treatments need be repeated periodically; however, for severe skin conditions or problems, stronger chemical treatments or more prolonged applications or laser therapy need be performed by aesthetic professionals or medical practitioners of the art, such as plastic surgeons or dermatologists.
Patents 169
Web site: http://www.delphion.com/details?pn=US06630442__ •
Reparatives for ultraviolet radiation skin damage Inventor(s): Hersh; Theodore (Atlanta, GA), Warshaw; Michael A. (Savannah, GA) Assignee(s): Thione International, Inc. (Altanta, GA) Patent Number: 6,337,320 Date filed: October 11, 1996 Abstract: A composition of L-glutathione (reduced) and selenium and an epidermal growth factor in a topical carrier and method of using the composition to reduce and repair ultraviolet radiation-induced skin damage, both acute injury (sunburn) and chronic damage (photoaging and cutaneous malignancies). Excerpt(s): The present invention deals with the combination of several anti-oxidants, including enzymatic co-factors and thiol compounds, and various tissue and cell growth stimulating factors in appropriate delivery vehicles employed in a topical carrier as a means of both minimizing and ameliorating and also concomitantly repairing free radical damage to the skin from ultraviolet radiation and also stimulating the growth, differentiation and maturation of epidermal cells resulting from environmental and metabolic factors. When cutaneous tissues are exposed to radiation such as solar ultraviolet rays (UVA and UVB radiation), damage to the skin ensues, particularly UVB which results in sunburn and tanning. Chronic UV ray exposure contributes to the skin aging process, the so-called photoaging process and in many cases to the development of cutaneous malignancies. Many common pathological factors exist as the various layers of skin are injured from local release of free radical species, emanating from cellular metabolism and enhanced by environmental UV radiation injury, while the skin is exposed to oxygen in the atmosphere as well as ozone, smog, smoke and other pollutants. The skin repair processes are common to environmental and dermatologic conditions. Cutaneous tissues so exposed to injury, such as UV radiation with resulting "burns," react so that water molecules contained within cells are altered as are lipids of membranes and of extracellular tissues resulting in the formation of a number of noxious free radicals. This phenomenon on the body has also been called oxidant stress and the free radicals are also known as reactive oxygen species. The latter two are known as the process of lipid peroxidation. Web site: http://www.delphion.com/details?pn=US06337320__
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Scr SH3 binding peptides and methods of isolating and using same Inventor(s): Der; Channing J. (Chapel Hill, NC), Kay; Brian K. (Chapel Hill, NC), Quilliam; Lawrence A. (Chapel Hill, NC), Sparks; Andrew B. (Carrboro, NC), Thorn; Judith M. (Carrboro, NC) Assignee(s): The University of North Carolina at Chapel Hill (Chapel Hill, NC) Patent Number: 6,303,574 Date filed: July 22, 1994 Abstract: Peptides having general and specific binding affinities for the Src homology region 3 (SH3) domains of proteins are disclosed in the present invention. In particular, SH3 binding peptides have been isolated from three phage-displayed random peptide
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libraries which had been screened for isolates that bind to bacterial fusion proteins of SH3 domains and glutathione S-transferase (GST). Preferred peptides are disclosed having a core 7-mer sequence (preferably, a consensus motif) and two or more, preferably at least six, additional amino acid residues flanking the core sequence, for a total length of 9, preferably at least 13, amino acid residues and no more than about 45 amino acid residues. Such peptides manifest preferential binding affinities for certain SH3 domains. The preferred peptides exhibit specific binding affinities for the Srcfamily of proteins. In vitro and in vivo results are presented which demonstrate the biochemical activity of such peptides. Excerpt(s): The present invention relates to SH3 binding peptides having a broad range of binding specificities. That is, certain members of the SH3 binding peptides disclosed bind with approximately the same facility with SH3 domains derived from different SH3 domain-containing proteins. Other members, in contrast, bind with a much greater degree of affinity for specific SH3 domains. The SH3 binding peptides are obtained from random peptide libraries that are also phage-displayed. Methods are described of obtaining the phage clones that bind to the SH3 domain targets and of determining their relevant nucleotide sequences and consequent primary amino acid sequence of the binding peptides. The resulting SH3 binding proteins are useful in a number of ways, including, but not limited to, providing a method of modulating signal transduction pathways at the cellular level, of modulating oncogenic protein activity or of providing lead compounds for development of drugs with the ability to modulate broad classes, as well as specific classes, of proteins involved in signal transduction. Among a number of proteins involved in eukaryotic cell signaling, there is a common sequence motif called the SH3 domain. It is 50-70 amino acids in length, moderately conserved in primary structure, and can be present 30 from one to several times in a large number of proteins involved in signal transduction and in cytoskeletal proteins. The protein pp60c-src represents a family of at least nine non-receptor protein tyrosine kinases (NR-PTKs). Members of this family share an overall structural organization comprising a series of catalytic and non-catalytic domains. In Src, a 14-amino-acid myristylation signal resides at the extreme amino-terminus, and is followed by a unique region that is not highly conserved among family members. Following this region are two highly conserved 60and 100-amino-acid regions, the Src homology (SH) domains 3 and 2, respectively. SH2 and SH3 domains have been shown to play an important role in mediating proteinprotein interactions in a variety of signaling pathways. Koch, C. A., et al., in Science (1991) 252:668-74. The carboxy-terminal half of Src contains the PTK catalytic domain, as well as a negative regulatory tyrosine (Y527) near the carboxy terminus. Phosphorylation of this residue (e.g., by Csk) results in the inhibition of PTK activity. Cooper, J. A., et al., in Science (1986) 231:1431-1434. Mutation of Y527.fwdarw.F generates forms of Src with increased PTK and oncogenic activity. Cartwright, C. A., et al., in Cell (1987) 49:83-91; Kmiecik, T. E., et al., in Cell (1987) 49:65-73; and PiwicnaWorms, H., et al., in Cell (1987) 75-82. Web site: http://www.delphion.com/details?pn=US06303574__
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Serum-free cell growth medium Inventor(s): Erlacher; Ludwig (Vienna, AT), Luyten; Frank P. (Kraainem, BE) Assignee(s): The United States of America as represented by the Department of Health and (Washington, DC) Patent Number: 6,617,161 Date filed: May 9, 2001 Abstract: A chemically defined-serum free growth medium for the in vitro and ex vivo of cells and cell lines. The medium consists of about a one to one ratio (v/v) of two basal growth media containing.alpha.-ketoglutarate, insulin, transferrin, selenium, bovine serum albumin, linoleic acid, ceruloplasmin, cholesterol, phosphatidylethanolamine,.alpha.-tocopherol acid succinate, reduced glutathione, taurine, triiodothyronine, hydrocortisone, parathyroid hormone, L-ascorbic acid 2-sulfate,.beta.glycerophosphate, PDGF, EGF and FGF. Chondrocytes, when cultured in this medium in the presence of a cartilage derived morphogenetic protein or bone morphogenetic protein, retain their cartilaginous phenotype. Excerpt(s): The present invention relates to a cell growth medium. More specifically, the invention relates to a chemically defined serum-free growth medium useful for the expansion of primary cells or cell lines in culture. Culturing of mammalian cells is an essential technique for research into cellular processes, production of recombinant therapeutic proteins, and generation of expanded cells for transplantation purposes. Cell culture studies have led to the determination of numerous metabolic processes and the identification of growth factors, hormones and their receptors (Bio Techniques, 5:534542, 1987). The composition of media used to culture cells is of paramount importance because of its influence on cell survival and cell response to various effectors. Conventional cell culture media comprise basal nutrient media supplemented with serum from various sources, most often fetal bovine serum, horse serum or human serum. However, the use of serum is undesirable for several reasons. Growth media containing serum may vary in composition, hormone content, and contaminants, thereby introducing extraneous factors and/or infections agents into the culture system (Bio Technology, 11:49-53, 1993; Pharm. Technol., 48:56, 1987). In addition, serum is expensive, impractical for large-scale production of therapeutics. Further, variance between serum lots and laboratory protocols is also a problem. Recent concerns by the FDA, the European community, and others about serum quality, contamination (i.e., bovine spongiform encephalopathy, bovine immunodeficiency virus), and increased demand have generated significant interest in the development and utility of serum-free growth media. Web site: http://www.delphion.com/details?pn=US06617161__
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Synergistic antioxidant veterinary compositions Inventor(s): Hersh; Theodore (Atlanta, GA) Assignee(s): Thione International, Inc. (Atlanta, GA) Patent Number: 6,303,651 Date filed: September 23, 1999 Abstract: A composition and method of treating cutaneous infection and resulting inflammation in animals known as hot spots and mange, respectively, as well as related
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veterinarian dermatological conditions. The composition includes L-glutathione and a source of selenium which act synergistically and which are included in a suitable topical carrier for topical application. Excerpt(s): The present invention deals with combinations of several synergistic antioxidants including enzymatic co-factors as adjunct to therapies of various mammals, particularly canine, feline and equine inflammatory conditions, including but not limited to thermal and chemical burns, various types of dermatitis, eczema infections and flea and mite induced cutaneous lesions, commonly known as "hot spots" and mange, respectively. These topical compositions are aimed at scavenging and neutralizing reactive oxygen species and other free radicals generated in the cutaneous inflammatory reactions being responsible for the animal's clinical symptoms and cutaneous lesions. These novel therapeutic compounds may be combined with other state of the art topical active ingredients such as zinc salts, anti-inflammatories (salicylates, non-steriodal anti-inflammatory drugs) corticosteroids, anti-microbials for the treatment of secondary bacterial or fungal infections and healing antioxidants such as zinc pyrithione and vitamins C and E. Canine eczema, clinically known as dermatitis rubric madidans, is one of the most difficult dermatologic problems to treat in veterinary medicine. Its pathogenesis is still rudimentary and multiple therapies are available to treat symptoms, while antibiotics quell secondary infections. Older literature refers to this entity as a moist and desquamating eczema or as infectious dermatitis, as the etiology was theorized to be Staphylococcus aureus as the putative pathogen. This Staph was cultured from early lesions, thus the term "infectious dermatitis." Staph toxins or an "allergic id" reaction were postulated as etiologic. Contact dermatitis might also play a role in this condition. Clinically, this eczema presents an acute discomfort, is persistent, and tends to recur. It is more frequent in the mature dog rather than in puppies. The lesions are of sudden onset and spread rapidly. The affected areas are very sensitive and extremely pruritic. The animal may have premonitory symptoms which include restlessness, anorexia, vomiting, and itching. Animals tend to persist in scratching, biting and rubbing the affected sensitive, moist lesions which become yellow to light red in color. Their efforts to obtain relief of the pruritus by scratching not only extends the depth and surface area of the dermatitis, but the excriations cause infection which extend to areas adjoining the original eczematoid site. Fever and lymph node enlargement may be noted. The course of this eczematoid reaction is variable, depending on the extent of the lesion, degree of destruction of the cutaneous tissues, severity of secondary infection and the animal's response to therapy. Web site: http://www.delphion.com/details?pn=US06303651__ •
Therapeutically effective substance mixture Inventor(s): Treusch; Gernot (Empuria Erava, Falconera 59, Castello d'Empories, ES) Assignee(s): none reported Patent Number: 6,448,227 Date filed: August 20, 2001 Abstract: A substance mixture, containing S-acetyl glutathione and Aciclovir, is effective as a medication against the Herpes Simplex virus and the Varicella Zoster virus. Excerpt(s): This invention relates to a mixture containing S-acetyl glutathione and Aciclovir (ACV) as medication against the Herpes Simplex virus or the Varicella Zoster
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virus. A process for the manufacture of S-acetyl glutathione is disclosed in U.S. Pat No. 2,760,956. Aciclovir (ACV) is a known medication for use against the Herpes Simplex virus (HSV). Aciclovir is an abbreviated nomenclature (INN) for 9-[(2hydroxyethoxy)methyl)guanine. Web site: http://www.delphion.com/details?pn=US06448227__ •
Treatment of chronic hypertension and related conditions with thiol complexes Inventor(s): Pearson; Don C. (Lakewood, WA), Richardson; Kenneth T. (Anchorage, AK) Assignee(s): Chronorx, LLC (Anchorage, AK) Patent Number: 6,429,219 Date filed: May 3, 2000 Abstract: This invention relates to the synthesis of certain complexes of cysteine, Nacetylcysteine, N-(2-mercaptopropionyl)glycine, and L-2-oxothiazolidine-4-carboxylate and to the nutritional use of these and other related individual or complexed thiolcontributing glutathione predecessors. Clinical uses for these molecules and complexes in the beneficial modification of various physiological conditions and functions associated with aging, chronic glaucoma, diabetes mellitus, insulin resistance, macular degeneration, neurodegenerative diseases and vasoconstriction are described in particular. Excerpt(s): This invention is in the fields of pharmacology and biochemistry. It relates to the synthesis of certain complexes of L-cysteine, N-acetyl L-cysteine, N-(2-mercaptopropionyl)glycine, L-2-oxothiazolidine-4-carboxylate and the nutritional or clinical use of these and other related individual or complexed thiol contributing, glutathione predecessors. The use of these molecules and complexes in clinical presentations of chronic glaucoma, diabetes mellitus, macular degeneration, neurodegenerative diseases and vasoconstriction are described in particular. The eye is maintained in a homeostatic shape by a relatively stable intraocular pressure (IOP) that varies within a reasonably narrow range so long as the intraocular production of aqueous fluid remains equal to its exit from the eye. The optic nerve head can tolerate relatively high levels of IOP if the availability of oxygen from posterior ciliary arteries and optic nerve head arterioles remains adequate. However, if the global intraocular pressure is higher than the perfusion pressure driving oxygen through the arteriole into the surrounding tissues, decreasing amounts of oxygen will reach the optic nerve head and nerve disability will result. Web site: http://www.delphion.com/details?pn=US06429219__
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Use of Phyllanthus for treating chronic inflammatory and fibrotic processes Inventor(s): Bahr; Matthias (Burgdorf, DE), Buniatian; Gayane Hrachia (Leipzig, DE), Gebhardt; Rolf (Leipzig, DE), Manns; Michael P. (Isernhagen, DE), Vollmar; Angelika M. (Munchen, DE), Wagner; Hildebert (Breitbrunn, DE) Assignee(s): Phytrix AG (Munich, DE) Patent Number: 6,586,015 Date filed: April 28, 2000
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Abstract: The present invention relates to the use of Phyllanthus for preventing or treating connective tissue proliferations, for maintaining the level of reduced glutathione, for inhibiting lipopolysaccharide (LPS)-induced nitric oxide synthase (NOS) and for inhibiting expression of the cyclooxygenase (COX-2) protein. Excerpt(s): The present invention relates to the use of Phyllanthus for preventing or treating connective tissue proliferations, for maintaining the level of reduced glutathione, for inhibiting the lipopolysaccharide (LPS)-induced nitric oxide synthase (NOS) and for inhibiting the expression of the cyclooxygenase (COX-2) protein. Phyllanthus embraces a widespread group of plants native to Central and South India, Taiwan, and areas of Central and South America. The term Phyllanthus means for the purpose of this invention all representatives of the botanical family of Phyllanthus, such as Phyllanthus niruri or, in particular, Phyllanthus amarus etc. The treatment of a large number of disorders with Phyllanthus is known in Indian folk medicine. Thus, for example, the author of "Doctor K. M. Nadkarni's Indian Materia Medica (3.sup.rd edition; revised and enlarged by A. K. Nadkarni)" reckons in volume I that the plant is known to be deobstruent, diuretic, astringent and cooling. Likewise, compositions with Phyllanthus are described for treating jaundice, dropsy, gonorrhoea, menorrhagia and other impairments of a similar type relating to the urogenital tract. Also known are the use of the sap from the trunk mixed with oil as ophthalmologicals or administrations for ulcers, wound sites and swellings etc., as well as the leaves for treating pruritus or other skin impairments. There is also known to be a large number of active substances which can be isolated from Phyllanthus, phyllanthin, hypophyllanthin, triacontanol, triacontanal, repandusinic acid A (see, for example, JP 03206044 A; AIDS-Res-HumRetroviruses (11/1992), vol. 8 (11), HIV-1 reverse transcriptase. ), phyllanthostatin-1, phyllanthoside, phyllanthocin, phyllanthocin acid (see, for example, EP 173 4480; U.S. Pat. No. 4,388,457), phyllamycin A, B and C, retrojusticidin B, justicidin A and B (see, for example, AIDS-Weekly, 25.9.95, AIDS Therapies Extracts. ), linoleic acid, linolenic acid and ricinoleic acid (see, for example, Journal of the American Oil Chemists Society edition 81.06.00, ricinoleic acid in Phyllanthus niruri. ), phyllamyricin D, E and F, phyllamyricoside A, B and C (see, for example, J. Nat. Prod. (11/1996), vol. 59 (11), Six lignans from. ), putranjivain A (see, for example, Chem. Pharm. Bull. (Tokyo), (04/1995), vol. 43 (4), Inhibitory effects of Egyptian. ), ursulic acid and niruriside (see, for example, J. Nat. Prod. 02/96, vol. 59 (2), Niruriside, a new HIV. , Rec. Trav. Chim. (06/1996), Synthesis of. ). Web site: http://www.delphion.com/details?pn=US06586015__ •
Zinc-monocysteine complex and method of using zinc-cysteine complexes Inventor(s): Newsome; David A. (1701 Oriole, New Orleans, LA 70122), Tate; David (5100 Marigny, New Orleans, LA 70122) Assignee(s): none reported Patent Number: 6,586,611 Date filed: January 8, 2001 Abstract: A method of providing zinc to a subject in need of treatment includes administering to the subject an effective amount of a zinc-cysteine complex. The zinccysteine complex is preferably a zinc-monocysteine complex. The complexes of zinccysteine of the present invention increase the activity of antioxidant enzymes catalase and glutathione peroxidase, and the antioxidant protein metallothionein. The
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complexes of zinc-cysteine of the present invention protect retinal pigment epithelial cells from increasing hydrogen peroxide concentrations. Excerpt(s): The present invention relates to nutritional supplements. More particularly, the present invention relates to nutritional supplements providing zinc to a subject in need of treatment. Zinc, an essential nutrient, is the second most abundant trace element in the human body and the most abundant trace element in the eye. It is necessary for the activity of more than 200 enzymes and for the DNA binding capacity of over 400 nuclear regulatory elements. There is evidence that zinc may function as an antioxidant by protecting sulfhydryl groups from oxidation, competing with copper and iron to reduce the formation of hydroxyl radicals which are a result of redox cycling and by the induction of the antioxidant protein metallothionein (MT) which can scavenge damaging hydroxyls. It has been suggested that oxidative stress and a decrease in antioxidant capacity play a role in several pathological conditions such as atherosclerosis, carcinogenesis, and macular degeneration. Age-related macular degeneration (AMD) is the number one cause of blindness in people over 60 in the United States. It is thought that it is an age-related defect in the retinal pigment epithelium (RPE) which contributes to this disease, however, the etiology is unknown and currently there is no cure. Our laboratory has previously reported that the antioxidants catalase, MT, and zinc decrease with age and signs of age-related macular degeneration in isolated human retinal pigment epithelial cells. Web site: http://www.delphion.com/details?pn=US06586611__
Patent Applications on Glutathione As of December 2000, U.S. patent applications are open to public viewing.9 Applications are patent requests which have yet to be granted. (The process to achieve a patent can take several years.) The following patent applications have been filed since December 2000 relating to glutathione: •
Amino acid derivatives and their use as medicines Inventor(s): Auvin, Serge; (Mauchamps, FR), Chabrier De Lassauniere, Pierre-Etienne; (Paris, FR), Harnett, Jeremiah; (Gif-Sur-Yvette, FR) Correspondence: Muserlian And Lucas And Mercanti, Llp; 600 Third Avenue; New York; NY; 10016; US Patent Application Number: 20030166630 Date filed: October 31, 2002 Abstract: The present invention relates to new derivatives of amino acids and their use as medicaments. These derivatives have an inhibitory activity on NO-synthase enzymes producing nitrogen monoxide NO and/or:either an activity which traps the reactive oxygen species;or an antioxidant regenerating activity such as glutathione or reactive oxygen species traps and more generally an influence on the redox status of the thiol groups. Excerpt(s): or an antioxidant regenerating activity such as glutathione or reactive oxygen species (ROS) traps and more generally an influence on the redox status of the thiol groups. or as agents allowing the regeneration of antioxidants such as glutathione
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This has been a common practice outside the United States prior to December 2000.
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or ROS traps entities and intervening in a more general fashion in the redox status of the thiol groups. all the pathologies characterized by a production or a dysfunction of nitrogen monoxide and/or ROS or the metabolism of glutathione and of the redox status of thiol groups. Web site: http://appft1.uspto.gov/netahtml/PTO/search-bool.html •
Anti-aging/menopause symptoms relief using ganoderma lucidum spores Inventor(s): Chung, Chee-Keung; (Kowloon, HK), Tong, Siu Kan; (Kowloon, HK) Correspondence: Venable, Baetjer, Howard And Civiletti, Llp; P.O. Box 34385; Washington; DC; 20043-9998; US Patent Application Number: 20030054014 Date filed: August 21, 2002 Abstract: The present invention provides a method for preventing/slowing aging and/or reducing menopause symptoms in humans by orally administering an effective amount of germination-activated Ganoderma lucidum spores (GLSs) to humans. The treatment for menopause is especially effective in male patients. GLSs are effective as an antioxidant to reduce free radical damage, particularly by increasing the amount of the reduced form glutathione (GSH) and the superoxide dismutase (SOD) activity. GLSs can also increase testosterone level in blood and improve depression, particularly geriatric depression, in elderly male patients. Excerpt(s): The present application is a continuation-in-part (CIP) of U.S. patent application Ser. No. 09/802,862, filed on Mar. 12, 2001, which is a divisional application of U.S. patent application Ser. No. 09/524,508, filed on Mar. 13, 2000 and issued as U.S. Pat. No. 6,316,002, which in turn claims the priority of U.S. provisional application No. 60/158,377, filed on Oct. 12, 1999, wherein all of the U.S. priority applications are herein incorporated by reference. The present invention relates to a method for preventing/slowing an aging process and/or reducing/relieving menopause symptoms in humans by orally administering an effective amount of germination-activated Ganoderma lucidum spores ("GLSs") to humans. The anti-aging effect of GLSs is primarily derived from its being an antioxidant for free radical protection. GLSs also reduce and/or relieve symptoms associated with menopause, particularly male menopause, which are partially due to aging. Symptoms associated with male menopause include fatigue, anorexia, palpitation, forgetfulness, irritation, depression, and/or impotence. The free radical theory of aging was first proposed by Dr. Denham Harman in 1956. It is now recognized that living cells continuously produce free radicals during their normal functions such as producing energy. Free radicals also come from smoking, radiation, sunlight and other factors in the environment. Endogenous and exogenous free radicals are highly reactive substances, capable of reacting irreversibly with many biological molecules, producing random changes, and causing progressive deterioration of the biological system. Web site: http://appft1.uspto.gov/netahtml/PTO/search-bool.html
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Antioxidant enzyme compositions for use with cigarettes Inventor(s): Hersh, Rebecca; (Atlanta, GA), Hersh, Theodore; (Atlanta, GA) Correspondence: Nathan P. Koenig; Crosby, Heafey, Roach & May; P.O. Box 7936; San Francisco; CA; 94120-7936; US Patent Application Number: 20020179103 Date filed: April 25, 2002 Abstract: A composition for inclusion within a cigarette, cigar, pipe or smokeless tobacco. The composition can be included within the tobacco itself, a filter for filtering tobacco smoke once burned or even within the paper or wrapper surrounding the tobacco product. In the cigarette filter, be it internal or external filters, the antioxidant complex is capable of scavenging and neutralizing the free radicals emanating from the burning or heated tobacco and passing through the filter as the smoker inhales. The composition is also capable of reducing free radical damage to the oro-pharyngeal cavity, respiratory tract and lungs resulting from tobacco smoke. The composition includes glutathione and preferaby L-glutathione and sources of the antioxidant enzymes catalase and superoxide dismutase. Excerpt(s): The present application is a continuation-in-part of U.S. application Ser. No. 09/185,172 filed Nov. 3, 1998 which, in turn, is a continuation-in-part of U.S. application Ser. No. 08/933,696, now U.S. Pat. No. 5,829,449. The present invention deals with the combination of various synergistic antioxidants, enzymatic co-factors and amino acids in appropriate delivery vehicles employed in cigarette filters and in external filters such as cigarette and cigar "holders," in "pipe filters" and in tobacco, wrappers and papers and in so-called smokeless tobacco as a means of preventing or ameliorating signs and symptoms and complications to the oro-pharyngeal cavity, respiratory tract and lungs from damage by tobacco smoke and tobacco chewed induced free radical species. The present invention can be employed in filter cigarettes, unfiltered cigarettes, cigars, pipes, and smokeless tobacco products. The deleterious effects of tobacco abuse are well known and regulatory agencies as well as the public constantly react to these scientific and epidemiologic evidences. Tobacco is indeed a worldwide public health hazard accounting for significant morbidity and mortality. Although smoking places an abundant oxidant insult to the oral cavity, respiratory tract and lungs, evidence supports the notion that the oxidant burden is on the entire organism of the smoker. Smoking promotes development or enhancement of atherosclerosis, causing cardiovascular disease, chronic obstructive pulmonary disease, recently labeled "smoker's lung," cutaneous damage, especially to the face, called "smoker's face," and various forms of cancer, including carcinomas of the mouth, pharynx, esophagus and lung. Web site: http://appft1.uspto.gov/netahtml/PTO/search-bool.html
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C-nitroso compounds and use thereof Inventor(s): Stamler, Jonathan S.; (Chapel Hill, NC), Toone, Eric J.; (Durham, NC) Correspondence: Eric S. Spector; Jones, Tullar & Cooper, P.C.; Eads Station; P.O. Box 2266; Arlington; VA; 22202; US Patent Application Number: 20030176668 Date filed: January 17, 2003
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Abstract: A C-nitroso compound having a molecular weight ranging from about 225 to about 1,000 (from about 225 to about 600 for oral administration) on a monomeric basis wherein a nitroso group is attached to a tertiary carbon, which is obtained by nitrosylation of a carbon acid having a pKa less than about 25, is useful as an NO donor. When the compound is obtained from a carbon acid with a pKa less than about 10, it provides vascular relaxing effect when used at micromolar concentrations and this activity is potentiated by glutathione to be obtained at nanomolar concentrations. When the compound is obtained from a carbon acid with a pKa ranging from about 15 to about 20, vascular relaxing effect is obtained at nanomolar concentrations without glutathione. The compound is preferably water-soluble and preferably contains a carbon alpha to the nitrosylated carbon which is part of a ketone group. In one embodiment, the C-nitroso compound is obtained by nitrosylation of a conventional drug or such drug modified to modify the carbon acid pKa thereof When such drug is a nonsteroidal anti-inflammatory drug, the resulting C-nitroso compound functions as a COX-1 and COX-2 inhibitor without the deleterious effects associated with COX-1 inhibition but with the advantageous effects associated with COX-1 and COX-2 inhibition. One such C-nitroso compound is a nitrosoketoibuprofen. A specific example of this kind of compound is isolated as dimeric 2-[4'-(.alpha.nitroso)isobutyrylphenyl]propionic acid. In another case, the C-nitroso compound contains the moiety 1where X is S, O or NR. One embodiment is directed to COX-2 inhibitors where a tertiary carbon atom and/or an oxygen atom and/or a sulfur atom is nitrosylated. Excerpt(s): The invention relates to C-nitroso compounds which are therapeutically active at low concentrations as NO donors. NO donors are known to be useful for therapeutic utility, e.g., to prevent restenosis following angioplasty (Groves, P., et al., Cardiovascular Research 26, 615-619 (1992)), to inhibit platelets to prevent coagulation and thrombus formation (Groves, P., et al., Circulation 87, 590-597 (1993)) and to treat angina (Knight, et al., Circulation 95, 125-132 (1997)). NO donors are considered to have additional therapeutic utility in cancer, killing microbes and viruses, relaxing airways and intestinal smooth muscle (e.g., for treating asthma and esophageal spasms), in promoting erectile function and in treatment of heart failure and urinary incontinence. NO donors are described in"Methods in Nitric Oxide Research," edited by Feelisch, M., and Stamler, J. S., John Wiley & Sons, New York, 1996 at pages 71-115. These NO donors are O-nitroso and S-nitroso compounds, and C-nitroso compounds that are excluded from the invention herein. Web site: http://appft1.uspto.gov/netahtml/PTO/search-bool.html •
Combination of treatment of cancer utilizing a COX-2 inhibitor and a 3-hydroxy-3methylglutaryl-coenzyme-a (HMG-CoA) reductase inhibitor Inventor(s): Guilford, F. Timothy; (Palo Alto, CA), Kindness, George; (Middletown, OH), Schumm, Brooke III; (Ellicott City, MD) Correspondence: Brooke Schumm Iii; One North Charles Street; Suite 2450; Baltimore; MD; 21014; US Patent Application Number: 20030162829 Date filed: March 17, 2003 Abstract: The inventors propose a combination of an HMG-CoA reductase inhibitor (also referred to as "HMG-CoA inhibitor(s)"), and COX-2 inhibitor for the treatment of cancer especially prostate cancer and a method of treatment of cancer by that
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combination, especially prostate cancer. The inventors propose a combination of an HMG-CoA reductase inhibitor, COX-2 inhibitor, and glutathione pathway enhancing and detoxifying compound, particularly cystine, for the treatment of cancer especially prostate cancer and a method of treatment of cancer by that combination, especially prostate cancer. Based on the clinical results of retardation, but not cure of cancer, the combination has the characteristic of sufficiently interfering with replication and apparently restoring the immune system capacity to manage cancer. Excerpt(s): This invention is a continuation-in-part of Provisional Application 60/263,486 filed Oct. 6, 2000, 60/245,592 filed Nov. 17, 2000, 60/264,511 filed Jan. 26, 2001, and a provisional application of this name filed on the same day as this application, which provisional applications are incorporated by reference. Traditional cancer treatments have generally used an approach which is focused on directly attacking cells with a propensity to divide. The cancer cell is viewed as a bad cell that must be eliminated. The methods and combinations chosen focus on destruction of the dividing cell, or chemical attack of the cell. Web site: http://appft1.uspto.gov/netahtml/PTO/search-bool.html •
Composition and method for substantially reducing the deleterious effects of alcohol on the body Inventor(s): Dobler, Peter Kevin; (Phoenix, AZ), Jones, Jeremy Park; (Tempe, AZ) Correspondence: Weiss & Moy PC; 4204 North Brown Avenue; Scottsdale; AZ; 85251; US Patent Application Number: 20030211172 Date filed: May 10, 2002 Abstract: A composition and method are provided for substantially preventing hangovers. The composition includes an effective amount of amino acids glycine and Glutathione, B vitamins and at least one mineral compound including each of magnesium, selenium, and molybdenum. Other vitamins, mineral compounds, flavorings, coloring, and solubility agents may also be added. Excerpt(s): This invention relates generally to a composition and method for substantially reducing the deleterious effects of alcohol on the body. More specifically, this invention relates to a composition and method for substantially preventing a hangover. Alcohol intoxication causes dehydration and an imbalance in electrolytes, minerals, and some vitamins in the bloodstream, disrupting many normal biological processes. In addition, if the level of alcohol is high in the blood, the liver becomes backed up and the enzymes responsible for detoxification then utilize secondary pathways of detoxification thereby producing toxic metabolites. These metabolites are much more toxic than alcohol and can cause nausea, headaches, and discomfort, usually collectively referred to as a "hangover." It has also been suggested that congeners worsen hangovers. "Congeners" are toxic byproducts of distillation and fermentation. Some spirits are higher in congeners than others. For example, red wine, brandies, and whiskies are usually higher than other types of alcohol. Hangovers have been plaguing mankind since time immemorial. The best approach to hangovers is to avoid them by not over imbibing in alcohol in the first place. This however is easier said that done. Hangovers are typically characterized by a throbbing headache, an upset stomach with nausea, dizziness and dry mouth. In addition to these physical consequences, hangovers have staggering economic and societal consequences. Billions are lost in the workplace
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due to low productivity and absenteeism due to hangovers. Moreover, people with hangovers experience diminished cognitive abilities that may pose a substantial threat to themselves and others, particularly in the workplace and while driving. Web site: http://appft1.uspto.gov/netahtml/PTO/search-bool.html •
Composition, synthesis and therapeutic applications of polyamines Inventor(s): MaLachowski, Mitchell R.; (San Diego, CA), Murphy, Michael A.; (La Jolla, CA) Correspondence: Charmasson & Buchaca; 1545 Hotel Circle South; Suite 150; San Diego; CA; 92108-3412; US Patent Application Number: 20030013772 Date filed: December 18, 2001 Abstract: The invention relates to the preparation of novel polyamines, such as derivatives of 1,3-bis-[(2'-aminoethyl)-amino]propane (2,3,2-tetramine) and 1,4,8,11tetraazacyclotetradecane (cyclam), which can be used to treat mitochondrial and degenerative diseases.Accordingly, in one aspect the invention is directed to compounds of the formula: 1whereinR.sub.1, R.sub.2, R.sub.3, R.sub.4, R.sub.5 and R.sub.6 may be the same or different and are hydrogen, alkyl, aryl, cycloalkyl, amino acid, glutathione, urate, ascorbate, estrogen, dehydroepiandrosterone, redox stabilizing substituents, a quinone, glutamate, succinate, -(CH.sub.2).sub.n[XCH.sub.2).sub.n]NH.sub.2-- wherein n=3-6 and X=nitrogen, sulfur, phosporous or carbon, or heterocycle wherein R.sub.1 to R.sub.6 taken together are -(CH.sub.2XCH.sub.2).sub.n-- wherein n=3-6 and X=nitrogen, sulfur, phosporous or carbon.M, n, and p may be the same or different and are bridging groups of variable length from 3-12 carbons.X.sub.1 and X.sub.2 may be the same or different and are nitrogen, sulfur, phosporous or carbon. Excerpt(s): This is a continuation-in-part of copending application Ser. No. 09/486,310 filed Feb. 23, 2000, issued from PCT application serial number US98/17301 filed Aug. 21, 1998 a continuation of application Ser. No. 08/915,660 filed Aug. 21, 1997, now U.S. Pat. No. 5,906,996. This invention relates to a process of synthesis and composition of open ring, closed ring, linear branched and or substituted polyamines for the treatment of neurological, cardiovascular, endocrine and other disorders in mammalian subjects, and more specifically to the therapy of Parkinson's disease, Alzheimer's disease, Lou Gehrig's disease, Binswanger's disease, Olivopontine Cerebellar Degeneration, Lewy Body disease, Diabetes, Stroke, Atherosclerosis, Myocardial Ischemia, Cardiomyopathy, Nephropathy, Ischemia, Glaucoma, Presbycussis and Cancer. There are two groups of polyamines described in herein, those derived from 1,3-bis-[(2'-aminoethyl)amino]propane (2,3,2-tetramine) and those from the macrocycle 1,4,8,11tetraazacyclotetradecane (cyclam). Of the collection of compounds described, most are not presently known but a few have been prepared previously. Web site: http://appft1.uspto.gov/netahtml/PTO/search-bool.html
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Compositions and methods for promoting a healthy cardiovascular system and enhancing blood flow Inventor(s): Yegorova, Inna; (Northridge, CA) Correspondence: Sierra Patent Group, LTD.; P O Box 6149; Stateline; NV; 89449; US Patent Application Number: 20020176900 Date filed: March 15, 2002 Abstract: Compositions and methods for promoting a healthy cardiovascular system and enhancing healthy blood flow by gently removing toxic buildup from the arterial walls and dilating and strengthening the arterial walls, in a mammal. The compositions comprise calcium; magnesium; selenium; manganese; zinc; potassium; vitamin E; vitamin A; alpha-lipoic acid; Allium sativum extract; Medicago sativa extract; Chondrus crispus extract; L-cysteine; L-glutamic acid; glycine; and glutathione. Excerpt(s): The present invention relates to compositions and methods for promoting a healthy cardiovascular system and enhancing healthy blood flow by, e.g., gently removing toxic buildup from the arterial walls and dilating and strengthening the arterial walls. Cardiovascular disease (CVD) is the leading cause of death in the industrialized countries. According to the American Heart Association, in 1997 alone, 59.7 million Americans were estimated to have one or more forms of cardiovascular disease including high blood pressure, coronary heart disease, stroke and rheumatic heart disease. Of those, 953,110 Americans died of some form of CVD, attributing 41.2% of all deaths to CVD. Coronary heart disease (CHD) by itself can be attributed to causing about half of all deaths associated with cardiovascular diseases (49%). The primary cause of CHD is artheriosclerosis, a degenerative change in the arteries whereby the arterial walls thicken and lose elasticity. One key process of artheriosclerosis is the accumulation of lipids resulting in distribution of atheromatous plaque. As plaque accumulates in the inner artery wall, the restricted artery is weakened, bulging with cholesterol and toxic deposits. Eventually, the plaque blocks the arteries and interrupts blood flow to the organs they supply. It is now well established that vascular blockage and cardiovascular disorders including myocardial infarction, coronary heart disease, hypertension and hypotension, cerebrovascular disorders including stroke, cerebral thrombosis and memory loss due to stroke; peripheral vascular disease and intestinal infarction are caused by blockage of arteries and arterioles by atherosclerotic plaque. The production of atherosclerotic plaque formation is multi-factorial in its production. Hypercholesterolemia, especially elevated levels of low-density lipoprotein cholesterol (LDL) is an important risk factor for atherosclerosis and arteriosclerosis and associated diseases. Web site: http://appft1.uspto.gov/netahtml/PTO/search-bool.html
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Cosmetic containing plant extracts Inventor(s): Fleury, Marie; (Paris, FR), Pauly, Gilles; (Nancy, FR) Correspondence: Young & Thompson; 745 South 23rd Street 2nd Floor; Arlington; VA; 22202 Patent Application Number: 20030072820 Date filed: May 14, 2002
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Abstract: A cosmetic composition containing plant extracts is disclosed. The composition has anti-free radical action, anti-aging and stimulates reduced glutathione auto-synthesis. The plant extracts are solvent extracts from Spondias mombin, Maprounea guianesis, Waltheria indica, Gouania blanchetiana, Cordia schmoburgkii, Randia armata and Hibiscus furcellatus. Excerpt(s): The invention concerns the cosmetics, more particularly the dermo-cosmetics field, and its subject is the use of plant extracts, found especially in Haut-Maroni (French Guiana), in the preparation of cosmetics for the skin, mucous membrane and/or exoskeleton (hair, nails,. ). The Aluku women (Haut-Maroni, French Guiana) traditionally carry out their ritual intimate ablutions every morning and evening with a plant decoction. specific to each stage of woman's life, using a large number of local plants. The plants are prepared by decoction then used in a hip bath according to the stage in the menstrual cycle and the required effect. Web site: http://appft1.uspto.gov/netahtml/PTO/search-bool.html •
Cytokine and hemopoietic factor endogenous production enhancer and methods of use thereof Inventor(s): Balazovski, Mark B.; (St. Petersburg, RU), Kozhemyakin, Leonid A.; (St. Petersburg, RU) Correspondence: Maria A. Trevisan; Wolf, Greenfield & Sacks, P.C.; Federal Reserve Plaza; 600 Atlantic Avenue; Boston; MA; 02210; US Patent Application Number: 20030027770 Date filed: April 18, 2002 Abstract: A method of stimulating endogenous production of cytokines and hemopoietic factors by introducing to a mammalian body in need of stimulation of cytokines or hemopoietic factors or both, an effective amount of oxidized glutathione and/or its therapeutically beneficial salts, and/or its therapeutically beneficial derivatives, for a period of time to stimulate said endogenous production to obtain a therapeutic effect. Oxidized glutathione with or without extenders are used in drug forms. Excerpt(s): This application is a continuation-in-part of our U.S. application Ser. No. 733886, filed Oct. 18, 1996. The present invention relates to medicine and more particularly to pharmacology and therapy, and is intended to be used for preventing and treating various diseases by way of increasing endogenous production of cytokines and hemopoietic factors. It has been known that a number of endogenously produced mammalian humoral factors, i.e. cytokines and hemopoietic factors possess important biological activities that are considerably helpful in treating various human diseases'. Many of these factors are being tested in man, those with proven efficiency being commercially available as medicinal agents. Web site: http://appft1.uspto.gov/netahtml/PTO/search-bool.html
Patents 183
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Derivatives of benzylidene cyclohexanone, benzylidene cyclopentanone, and benzylidene acetone, and therapeutic uses thereof Inventor(s): Hakim, Arief Rahman; (Yogyakarta, ID), Hakim, Lukman; (Yogyakarta, ID), Margono, Supardjan Amir; (Yogyakarta, ID), Martono, Sudibyo; (Yogyakarta, ID), Nurlaila; (Yogyakarta, ID), Nurrochmad, Arief; (Yogyakarta, ID), Oetari; (Yogyakarta, ID), Purwantiningsih; (Yogyakarta, ID), Puspitasari, Ika; (Yogyakarta, ID), Reksohadiprodjo, Mochammad Samhoedi; (Yogyakarta, ID), Sardjiman; (Yogyakarta, ID), Sugiyanto; (Yogyakarta, ID), Timmerman, Henk; (Yogyakarta, ID), Yuwono, Tedjo; (Yogyakarta, ID) Correspondence: Lahive & Cockfield; 28 State Street; Boston; MA; 02109; US Patent Application Number: 20030092772 Date filed: February 27, 2002 Abstract: Benzylidene cyclohexanone, cyclopentanone and acteone derivatives and therapeutic methods of using same are disclosed. The compounds are non-toxic and exhibit potent anti-inflammatory, antibacterial and antioxidation activity. Also, certain compounds of the invention inhibit glutathione S-transferase ("GST"), but do not irritate the gastrointestinal tract. Pharmaceutical compositions containing the compounds of the invention and pharmaceutically acceptable carriers are also disclosed. Excerpt(s): This application is a continuation-in-part of pending U.S. patent application Ser. No. 09/747,585, entitled, "Derivatives of Benzilidine Cyclohexanone, Benzilidine Cyclopentanone, and Benzilidine Acetone and their Synthesis," filed on Dec. 21, 2000, which is a continuation of allowed U.S. patent application Ser. No. 09/026,624, entitled "Derivatives of Benzilidine Cyclohexanone, Benzilidine Cyclopentanone, and Benzilidine Acetone and their Synthesis," filed on Feb. 20, 1998, which claims priority to Indonesian Patent Application Serial No. P-970482, filed on Feb. 20, 1997. The disclosures of all of the aforementioned patent applications are expressly incorporated herein by reference. The invention relates to benzylidene derivatives, and more particularly to benzylidene cyclohexanone, benzylidene cyclopentanone, and benzylidene acetone, and derivatives thereof. The invention also relates to the biological activities of the aforementioned compounds in vivo and in vitro, pharmaceutical compositions thereof, and therapeutic methods of administration of same in animals. Thus, curcumin has been widely used medicinally as an anti-inflammatory, antibacterial, antioxidant, anti-hepatotoxic, hypochlolesterolanemia, anti-cyclooxygenase, anti-cancer, and radical scavenger agent. However, it has been reported that curcumin is not stable in an alkali (pH>6.5) solution. Web site: http://appft1.uspto.gov/netahtml/PTO/search-bool.html
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Dietary supplement Inventor(s): Coleman, Henry D.; (Hastings, NY), Sapone, William J.; (Southport, CT), Sudol, R. Neil; (Scarsdale, NY) Correspondence: William J. Sapone, ESQ.; Coleman Sudol Sapone P.C.; 714 Colorado AVE.; Bridgeport; CT; 06605; US Patent Application Number: 20030194453 Date filed: April 15, 2002
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Abstract: A dietary supplement for removing or preventing the bio-accumulation of heavy metals in the body includes a primary chelator, a secondary chelator, and optionally a tertiary chelator or a precursor of a tertiary chelator. The primary chelator preferably crosses the blood brain barrier to capture a heavy metal ion from a site in the central nervous system. The primary chelator then crosses back through the blood brain barrier with the entrained heavy metal ion. The secondary chelator binds the heavy metal from or with the primary chelator for removal. In one embodiment, a tertiary chelator such as glutathione or metallothionine assists in moving the chelated heavy metal out into an excretion pathway. Using the dietary supplement limits the accumulation of heavy metals in the body, promotes removal of heavy metals previously accumulated in the body and alleviates the symptoms and conditions associated with heavy metal toxicity. Excerpt(s): This invention is directed to a dietary supplement. More particularly, this invention is directed to a dietary supplement for assisting the body in cleansing itself of undesirable metals. Mercury has been implicated in a vast array of disorders and diseases, from vascular disease to immunological malfunctions, from renal dysfunction to autism and related neurological disorders such as attention deficit disorder. Lead, arsenic and cadmium are also known to be toxic in any substantial quantities. High levels of heavy metals such as mercury and lead are most common in people who have been exposed to high concentrations of the metals, for example, those individuals who have had the misfortune of living in a toxic waste area or near a chemical processing plant. However, even people exposed to small concentrations of a heavy metal can, over time, accumulate dangerous levels of the substance. This long term exposure has evidently occurred in children who received a series of vaccinations preserved with a mercury containing compound. Although no single vaccination likely contained enough mercury to cause any damage, the accumulation of mercury from multiple vaccinations over a two or three year period resulted in dangerous levels of mercury in a significant percentage of children. Web site: http://appft1.uspto.gov/netahtml/PTO/search-bool.html •
Disruption of the glutathione S-transferase-Omega-1 gene Inventor(s): Allen, Melanie R.; (Old Lyme, CT), Audoly, Laurent P.; (Groton, CT), Gabel, Christopher A.; (Ledyard, CT) Correspondence: Pfizer INC.; Patent Department, Ms8260-1611; Eastern Point Road; Groton; CT; 06340; US Patent Application Number: 20030131370 Date filed: November 18, 2002 Abstract: The invention features non-human mammals and animal cells that contain a targeted disruption of a glutathione S-transferase-Omega-1 gene. The invention also features methods of treating an IL-1 mediated and/or inflammation mediated disorder in a mammal comprising administering an agent that inhibits GST-Omega-1 activity. Excerpt(s): This application claims priority, under 35 U.S.C.sctn.119(e), from provisional application 60/341,483 filed Dec. 14, 2001. The present invention features geneticallymodified non-human mammals and animal cells containing a disrupted glutathione Stransferase-Omega-1 (GST-Omega-1) gene. The glutathione S-transferases (GSTs) are a family of phase II enzymes that utilize glutathione in biotransformation reactions that dispose of a wide variety of compounds, including chemical carcinogens, therapeutic
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drugs, and the products of oxidative stress (Board et al., J. Biol. Chem. 275: 24798-806, 2000). Web site: http://appft1.uspto.gov/netahtml/PTO/search-bool.html •
Expression systems utilizing autolyzing fusion proteins and a novel reducing polypeptide Inventor(s): Kawashima, Ichiro; (Tokyo, JP), Koishi, Ryuta; (Tokyo, JP), Serizawa, Nobufusa; (Tokyo, JP), Takahashi, Tohru; (Tokyo, JP) Correspondence: Frishauf, Holtz, Goodman & Chick, PC; 767 Third Avenue; 25th Floor; New York; NY; 10017-2023; US Patent Application Number: 20030176688 Date filed: April 25, 2001 Abstract: The present invention provides expression systems for exogenous polypeptides wherein the polypeptide is expressed as a fusion protein together with clover yellow virus Nuclear Inclusion a (NIa), the NIa component serving to autolyze the fusion protein after expression. This system can be used to express a novel polypeptide which we have designated KM31-7 protein and which is capable of reducing dichloroindophenol and reduced glutathione. This polypeptide is useful in the treatment of disorders caused by oxidative stress. Excerpt(s): The present invention relates to polypeptide expression systems requiring cleavage of a precursor product, and to proteases for use in such systems. The present invention further relates to a novel polypeptide capable of reducing dichloroindophenol and oxidized glutathione, DNA encoding the novel polypeptide, vectors containing such DNA, hosts transformed with such vectors, and pharmaceutical compositions containing the polypeptide. In addition, the present invention also relates to monoclonal antibodies against this polypeptide, and a process for isolating and purifying the polypeptide using such an antibody. The Potyviruses are a group of viruses each of which have a single-stranded, RNA genome of approximately 10,000 bases and which infects plants such as the family Solanaceae. The Potyvirus genome is characterized by possessing one extremely long open reading frame, or ORF, [Dougherty, W. G. and Hiebert, E. (1980), Virology 101: 466-474.; Allison, R. et al. (1986), Virology 154: 9-20]. In order to express the individual proteins encoded within the ORF, the translated polyprotein is digested by two types of protease, both of which are also encoded within the ORF [Dougherty, W. G. and Carrington, J. C. (1988), Ann. Rev. Phytopath. 26: 23143]. Tobacco etch virus (TEV) is a member of the Potyvirus family, and this virus produces nuclear inclusions which can be stained with trypan blue in the infected cell. The nuclear inclusions apparently consist of two kinds of protein, one of which has proven to be a viral protease, and which has been designated Nuclear Inclusion a, or NIa [J. Virol., 61: 2540-2548 (1987)]. Web site: http://appft1.uspto.gov/netahtml/PTO/search-bool.html
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Fusion protein arrays on metal substrates for surface plasmon resonance imaging Inventor(s): Corn, Robert M.; (Madison, WI), Erickson, Matthew G.; (Madison, WI), Smith, Emily A.; (Madison, WI), Ulijasz, Andrew T.; (Madison, WI), Wanat, Matthew J.; (Madison, WI), Weisblum, Bernard; (Madison, WI) Correspondence: Dewitt Ross & Stevens S.C.; 8000 Excelsior DR; Suite 401; Madison; WI; 53717-1914; US Patent Application Number: 20030100127 Date filed: March 15, 2002 Abstract: Disclosed are methods for making surface plasmon resonance-capable arrays wherein molecules, such as proteins or nucleic acids, or cells, are adhered to a metal substrate. The metal substrates are modified by depositing an.omega.-modified alkanethiol monolayer to the substrate and then contacting the.omega.-modified monolayer with a heterobifunctional linking compound. Biomolecules or cells can then be attached to the heterobifunctional linking compound. Also disclosed are arrays wherein glutathione-containing molecules are immobilized on the substrate and GSTcontaining molecules are then specifically immobilized onto the substrate, taking advantage of the affinity between glutathione and GST. Excerpt(s): Priority is hereby claimed to provisional application Serial No. 60/xxx,yyy, filed Mar. 6, 2002, and Ser. No. 60/304,246, filed Jul. 10, 2001, the contents of both of which are incorporated herein by reference. The invention is directed to methods of fabricating fusion protein arrays on metal surfaces, the arrays so formed, and a method of analyzing proteins via surface plasmon resonance. Complete bibliographic citations to the references described herein can be found in the Bibliography section, immediately preceding the claims. All of the references cited herein are incorporated by reference. Web site: http://appft1.uspto.gov/netahtml/PTO/search-bool.html
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Generic capture elisa using recombinant fusion proteins for detecting antibodies in biological samples Inventor(s): Gaenzler, Christof; (Nussloch, DE), Pawlita, Michael; (Eschelbronn, DE), Sehr, Peter; (Heidelberg, DE) Correspondence: Heller Ehrman White & Mcauliffe Llp; 1666 K Street,nw; Suite 300; Washington; DC; 20006; US Patent Application Number: 20030044870 Date filed: July 12, 2002 Abstract: The present invention relates to a generic capture ELISA for the detection and measurement of antibodies in biological fluids such as serum. This newly developed enzyme-linked immunosorbent assay (ELISA) system uses a first binding partner of a binding pair, preferably glutathione, crosslinked to casein as capture protein to bind recombinant protein antigens fused to a second binding partner of said binding pair, preferably N-terminal glutathione S-transferase (GST). The method not only allows the specific and efficient detection of antibodies in biological samples but, in addition, simple and efficient immobilization and one-step purificaton of overexpressed recombinant antigens even from crude lysates on ELISA plates coated with the first binding partner/casein. Several antigens can be tested in parallel under the same conditions without the need to biochemically purify or renature the proteins.
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Excerpt(s): The present invention relates to a generic capture ELISA for detecting and/or quantifying antibodies in biological samples. The present invention provides a specific and sensitive method of detecting antibodies in biological samples. This capture ELISA was developed in particular, for the detection of antibodies to recombinant GSTfused polypeptides in serum. This method, however, is generally applicable to other biological samples such as plasma, saliva, urine, milk, semen, tears, lymph, spinal fluids, ascites, peritoneal and other effusions and vaginal secretions etc. and also to laboratory fluids such as tissue culture supernatans or cell lysates. Enzyme-linked immunosorbent assays (ELISA) for the detection of antibodies to protein antigens often use direct binding of short synthetic peptides to the plastic surface of a microtitre plate. The peptides are, in general, very pure due to their synthetic nature and efficient purification methods using high-performance liquid chromatography. A drawback of short peptides is that they usually represent linear, but not conformational or discontinuous epitopes. To present conformational epitopes, either long peptides or the complete native protein are used. Direct binding of the protein antigens to the hydrophobic polystyrene support of the plate can result in partial or total denaturation of the bound protein and loss of conformational epitopes. Coating the plate with an antibody, which mediates the immobilization (capture ELISA) of the antigens, can avoid this effect. However, frequently, overexpressed recombinant proteins are insoluble and require purification under denaturing conditions and renaturation, when antibodies to conformational epitopes are to be analyzed. Web site: http://appft1.uspto.gov/netahtml/PTO/search-bool.html •
Herbicide resistant plants Inventor(s): Hawkes, Timothy Robert; (Bracknell, GB), Jepson, Ian; (Bracknell, GB), Knight, Mary Elizabeth; (Norwich, GB), Thomas, Paul Graham; (Bracknell, GB), Thompson, Paul Anthony; (Bracknell, GB) Correspondence: Hale And Dorr Llp; 60 State Street; Boston; MA; 02109; US Patent Application Number: 20030041357 Date filed: February 23, 2001 Abstract: The present invention provides inter alia, a polynucleotide comprising at least a first region encoding a first protein capable of conferring on a plant, or tissue comprising it, resistance or tolerance to a first herbicide, and a second region encoding a second protein likewise capable of conferring resistance to a second herbicide, with the provisos (i) that the polynucleotide does not encode a fusion protein comprising only a 5-enol-pyruvyl-3-phosphoshikimate synthetase (EPSPS) and a glutathione S transferase (GST); (ii) that the polynucleotide does not comprise only regions encoding superoxide dismutase (SOD) and glutathione S transferase (GST), and (iii) that the polynucleotide does not comprise only regions encoding GST and phosphinothricin acetyl transferase (PAT). Excerpt(s): The present invention relates to recombinant DNA technology, and in particular to he production of transgenic plants which exhibit substantial resistance or substantial tolerance to herbicides when compared with non transgenic like plants. Plants which are substantially "tolerant" to a herbicide when they are subjected to it provide a dose/response curve which is shifted to the right when compared with that provided by similarly subjected non tolerant like plants. Such dose/response curves have "dose" plotted on the x-axis and "percentage kill", "herbicidal effect" etc. plotted on the y-axis. Tolerant plants will require more herbicide than non tolerant like plants in
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order to produce a given herbicidal effect. Plants which are substantially "resistant" to the herbicide exhibit few, if any, necrotic, lytic, chlorotic or other lesions when subjected to the herbicide at concentrations and rates which are typically employed by the agrochemical community to kill weeds in the field. Plants which are resistant to a herbicide are also tolerant of the herbicide. The terms "resistant" and "tolerant" are to be construed as "tolerant and/or resistant" within the context of the present application. According to the present invention there is provided a polynucleotide comprising at least a first region encoding a first protein capable of conferring on a plant, or tissue comprising it, resistance or tolerance to a first herbicide, and a second region encoding a second protein likewise capable of conferring resistance to a second herbicide, with the provisos (i) that the polynucleotide does not encode a fusion protein comprising only a 5-enol-pyruvyl-3-phosphoshikima- te synthetase (EPSPS) and a glutathione S transferase (GST); (ii) that the polynucleotide does not comprise only regions encoding superoxide dismutase (SOD) and glutathione S transferase (GST). and (iii) that the polynucleotide does not comprise only regions encoding GST and phosphinothricin acetyl transferase (PAT). Web site: http://appft1.uspto.gov/netahtml/PTO/search-bool.html •
Human cellular protein gastrointestinal glutathione peroxidase as target for medical intervention against hepatitis C virus infections Inventor(s): Cotten, Matthew; (Munchen, DE), Herget, Thomas; (Planegg, DE), Obert, Sabine; (Munchen, DE) Correspondence: Leon R. Yankwich; Yankwich & Associates; 201 Broadway; Cambridge; MA; 02129; US Patent Application Number: 20030180719 Date filed: January 14, 2003 Abstract: The present invention relates to the human cellular protein glutathione peroxidase-gastrointestinal as a target for medical intervention against Hepatitis C virus (HCV) infections. Furthermore, the present invention relates to a method for the detection of compounds useful for prophylaxis and/or treatment of Hepatitis C virus infections and a method for detecting Hepatitis C virus infections in an individual or in cells. Also compositions, compounds, nucleic acid molecules (such as aptamers), monoor polyclonal antibodies are disclosed which are effective for the treatment of HCV infections, and methods for prophylaxis and/or treatment of Hepatitis C virus infections or for the regulation of Hepatitis C virus production are disclosed. Excerpt(s): The present application is a continuation-in-part of copending international application PCT/EP02/04167, filed Apr. 15, 2002, which claims priority to U.S. provisional application 60/283,345, filed Apr. 13, 2001. The present application also claims priority to German application DE 102 55 861.2 filed Nov. 29, 2002 and to U.S. provisional application No. 60/xxx,xxx filed Dec. 3, 2002. The present invention relates to the human cellular protein glutathione peroxidase-gastrointestinal (or gastrointestinal glutathione peroxidase, abbreviated GI-GPx) as a potential target for medical intervention against Hepatitis C virus (HCV) infections. Furthermore, the present invention relates to a method for the detection of compounds useful for prophylaxis and/or treatment of Hepatitis C virus infections and a method for detecting Hepatitis C virus infections in an individual or in cells. Also mono- or polyclonal antibodies are disclosed that are effective for the treatment of HCV infections together with methods for treating Hepatitis C virus infections or for the regulation of Hepatitis
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C virus production wherein genes or said antibodies may be used. The present invention also relates to chemical compounds and substances which are effective against Hepatitis C virus (HCV) infections. In particular, compositions comprising said compounds and/or substances, use of the compounds and/or substances for the preparation of compositions useful for the prophylaxis and/or treatment of HCV infections, as well as methods for preventing and/or treating HCV infections. Web site: http://appft1.uspto.gov/netahtml/PTO/search-bool.html •
Immunomodulator Inventor(s): Hamuro, Junji; (Kawasaki-shi, JP), Murata, Yukie; (Kawasaki-shi, JP) Correspondence: Oblon, Spivak, Mcclelland, Maier & Neustadt, P.C.; 1940 Duke Street; Alexandria; VA; 22314; US Patent Application Number: 20030203006 Date filed: April 3, 2003 Abstract: An immunomodulator is provided which is capable of oral intake for improvement, treatment and prevention of human immunological diseases and which is used to treat, improve and prevent human immunological diseases, especially, autoimmune diseases and allergic diseases such as hepatic cirrhosis, hepatitis, diabetes, inflammatory bowel diseases, chronic rheumatoid arthritis, asthma and cutaneous atopy, allergic diseases and cancers by a new method that can control the redox state of macrophages or monocytes, and can be incorporated into a drug, a food, a nutrient, and an infusion. The contents of oxidative glutathione and reductive glutathione in macrophages are monitored, and the ratio of oxidative glutathione and reductive glutathione is examined, whereby macrophages are classified into oxidative macrophages and reductive macrophages having different functions. The degree of progression of various autoimmune diseases is analyzed from this standpoint. On the basis of the results, an immunomodulator capable of oral intake which contains a substance having an activity of changing a content of reductive glutathione in macrophages to solve the above-mentioned problem and which is intended to treat, improve and prevent human immune diseases is provided. Excerpt(s): The present invention relates to a novel immunomodulator. More specifically, the present invention relates to an immunomodulator capable of oral intake which has a novel suppressive function of macrophages (hereinafter sometimes abbreviated as "M.PHI.") or monocytes. The immunomodulator may be used for treatment, improvement and prevention of human autoimmune diseases such as hepatic cirrhosis, hepatitis, diabetes, inflammatory bowel diseases, chronic rheumatoid arthritis, asthma and cutaneous atopy, allergic diseases and cancers. The present invention also relates to a drug, a food, a nutrient and an infusion containing the immunomodulator. As used herein, the term "immune system" refers to one's bodily system for defending itself from exogenous infection by virus, bacteria or the like, or from invasion the body with transformed cells (tumor cells and the like) formed by transformation of autologous cells. However, the immune system occasionally behaves abnormally, i.e., it functions excessively and acts to reject autologous components. On the other hand, the immune system sometimes functions deficiently, resulting in an immunocompromised state. Diseases revealing these abnormal responses are generally called immunological diseases. Examples thereof include diverse diseases, such as, for example, acute or chronic inflammatory diseases such as atopic cutaneous inflammatory diseases, pollinosis, asthma and sarcoidosis; autoimmune diseases such as allergic diseases,
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chronic rheumatoid arthritis, diabetes, SLE and chronic fatigue syndrome; hepatitis, hepatic cirrhosis, inflammatory bowel diseases (IBD) such as ulcerative colitis and Crohn's disease; and cancer cachexia. These immunological diseases originate from complex pathological causes. Systemic immunodeficiency and functional deficiency originate from pathological inflammation accompanied by cell proliferation, differentiation or cell necrosis through local production of cytokines or inflammatory mediators. As cells that participate in immunity, T lymphocytes and B lymphocytes are well known, exhibiting a wide variety of functions as cells playing roles in cellular immunity and humoral immunity respectively. Meanwhile, macrophages and monocytes are cells that intimately participate in both cellular immunity and humoral immunity, and they intimately participate in rejection of non-self foreign bodies, for example, immunological diseases such as allergy and rheumatism, cancers and bacterial infection. Web site: http://appft1.uspto.gov/netahtml/PTO/search-bool.html •
Immunopotentiators Inventor(s): Hatao, Masato; (Yokohama-Shi, JP), Iwai, Ichiro; (Yokohama-Shi, JP), Naganuma, Masako; (Yokohama-Shi, JP), Wada, Genji; (Yokohama-Shi, JP), Yagi, Eiichiro; (Yokohama-Shi, JP), Yamaguchi, Kenji; (Yokohama-Shi, JP) Correspondence: Townsend & Banta; Suite 500 #50028; 1225 Eye Street, N.W.; Washington; DC; 20005; US Patent Application Number: 20030086879 Date filed: May 7, 2002 Abstract: An immunopotentiator for preventing ultraviolet light-induced skin immunosuppression or a drug against ultraviolet light-induced skin immunosuppression which contains glutathione or Scutellaria root extract. Also, an immunopotentiator or a drug against immunosuppression which contains linden extract, clove extract, Geranium herb extract or rosemary extract. They can prevent a reduction of immune functions due to ultraviolet light. Excerpt(s): The present invention relates to a skin immunopotentiator or an endermic liniment against ultraviolet light-induced skin immunosuppression for preventing skin immunosuppresion due to exposure to ultraviolet light by external application. Skin is an organ which is located in the outermost layer of a living body and it also is an organ which incurs physical, chemical and biological invasion most intensely and directly. Recently it has become clear that the skin is also the most well developed immune organ. The skin consists of corneum cells of the epidermis, Langerhans' cells, dendritic cells of the corium, vascular endothelial cells, macrophages, etc. The Langerhans' cells are believed to play a central role in skin immune function by their ability to process and present antibodies. It is believed that they promptly contact and deal with an antigen which has entered from the outside as a foreign entity and then move to lymph glands and present the antigen to the T cells, initiating a subsequent series of immune response reactions. Web site: http://appft1.uspto.gov/netahtml/PTO/search-bool.html
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Kidney perfusion solution containing nitric oxide donor Inventor(s): Gage, Frederick A.; (Kensington, MD), Vodovotz, Yoram; (Sewickley, PA) Correspondence: James C Lydon; Suite 100; 100 Daingerfield Road; Alexandria; VA; 22314; US Patent Application Number: 20030104348 Date filed: August 28, 2002 Abstract: A kidney perfusion solution which includes at least one gluconate salt; glutathione; a nitric oxide donor chemical and a chemical inhibitor selective for the inducible isoform of the enzyme nitric oxide synthase; optionally further containing a reagent that causes the reduction of oxidized glutathione. A process for preserving a kidney for transplantation is also disclosed, which includes perfusing the kidney with an amount of a nitric oxide donor chemical in an amount sufficient to mimic enzymatic production of NO by NOS3 or NOS1, while preventing generation of an excessive amount of nitric oxide by the NOS2 isoform of nitric oxide synthase, with or without a reagent that causes the reduction of oxidized glutathione. The invention also includes a process wherein a deceased donor's body is perfused with a solution containing an NO donor, with or without a reagent that causes the reduction of oxidized glutathione, prior to removal of the organs for transplantation. Excerpt(s): This invention relates to kidney perfusion solutions and a method for increasing the viability of perfused kidneys prior to transplantation. Kidneys must be preserved for a period of at least 5 hours prior to transplantation to obtain proper pathology assessment of the suitability of the organ for transplantation. Lack of proper preservation leads to degradation of organ function due to thrombosis (blood clotting), ischemia (lack of oxygen), or ischemia followed by reperfusion (the restoration of blood flow upon transplantation). These events bring about inflammation, cell death, and eventually failure of the organ. The preferred method for preserving kidneys is pulsatile preservation. Pulsatile kidney preservation is a process in which the renal artery is connected to a kidney perfusion machine in order to simulate the normal process by which nutrients are supplied to the kidney. A solution is continuously perfused through a closed circuit which includes the kidney, which is typically maintained at 5 degrees C. In order for pulsatile preservation to be an effective method for preservation of "extended criteria" organs (i.e., organs which are less optimal than those currently accepted for transplantion), the technician needs to monitor closely not just perfusion pressure, flow, and vascular resistance, but also the organ's chemistries, including base excess, oxygen saturation, calcium, potassium, hematocrit, pO.sub.2, pH, and bicarbonate. This method has become the standard of care for kidney transplantation, due to its efficacy and cost effectiveness. See Light et al., "Immediate function and cost comparison between static and pulsatile preservation in kidney recipients," Clin. Transplantation 233-236 (1996). Web site: http://appft1.uspto.gov/netahtml/PTO/search-bool.html
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Method for predicting the sensitivity to chemotherapy Inventor(s): Christina Rosa Geroni, Maria; (Milan, IT), Fowst, Camilla; (Milan, IT), Tursi, Jennifer Margaret; (Milan, IT), Vreeland, Franzanne; (Martinsville, NJ) Correspondence: Arent Fox Kintner Plotkin & Kahn; 1050 Connecticut Avenue, N.W.; Suite 400; Washington; DC; 20036; US Patent Application Number: 20030096325 Date filed: September 26, 2001 Abstract: Herewith described is a novel method for predicting the sensitivity towards chemotherapy, of a patient in need thereof, which comprises obtaining a blood sample from the patient and detecting the levels of blood glutathione (GSH) as a surrogate marker for glutathione-S-transfera- se (GST) activity in tumor tissues. Excerpt(s): The present invention relates to the field of cancer treatment and more particularly, it relates to a method for predicting the sensitivity towards chemotherapy of a patient, by measuring glutathione (GSH) blood levels of the said patient undergoing chemotherapeutic treatment. The levels of glutathione (GSH) or GSHrelated enzyme glutathione-transferase (GST) are known in the art to be correlated with the response to cytotoxic antitumor treatments since high levels of GSH or GST confer resistance to several antitumor drugs such as, for instance, alkylating agents (e.g. melphalan, chlorambucil, cyclophosphamide, ifosfamide mustards, BCNU), platinum complexes (e.g. cisplatin, carboplatin and oxaliplatin) and anthracyclines (e.g. doxorubicin, epirubicin, idarubicin and daunorubicin) [Biochem. Pharmacol 35: 34053409 (1986)]. Both GSH and GST are ubiquitously present in several human tissues such as, for instance, blood cells, plasma, serum, circulating blasts and pathologic (tumor) tissues. Web site: http://appft1.uspto.gov/netahtml/PTO/search-bool.html
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Method for producing gamma-glutamylcysteine Inventor(s): Nishiuchi, Hiroaki; (Kanagawa, JP), Sano, Kouichiro; (Kanagawa, JP), Sugimoto, Reiko; (Kanagawa, JP), Ueda, Yoichi; (Kanagawa, JP) Correspondence: Oblon, Spivak, Mcclelland, Maier & Neustadt, P.C.; Fourth Floor; 1755 Jefferson Davis Highway; Arlington; VA; 22202; US Patent Application Number: 20030124684 Date filed: January 25, 2002 Abstract: Yeast extract is produced by using a strain of Saccharomyces cerevisiae, which can contain 1% by weight or more of.gamma.-glutamylcysteine and contains 0.004-0.1% by weight of glutathione during its logarithmic growth phase, when the strain is cultured in a medium in which a glutathione synthetase deficient strain shows a slower growth rate than a wild strain of Saccharomyces cerevisiae, for example, a strain of Saccharomyces cerevisiae, wherein glutathione synthetase encoded by a glutathione synthetase gene on a chromosome has deletion of a C-terminus region from the 370th arginine residue. There are provided yeast that can be used for production at industrial level and shows a high.gamma.-glutamylcysteine accumulation amount, and yeast extract produced by using the yeast. Excerpt(s): The present invention relates to yeast and yeast extract having a high.gamma.-glutamylcysteine content as well as a method for breeding such
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yeast.gamma.-Glutamylcysteine and cysteine produced therefrom are useful in the food industry. Cysteine is used for the purpose of improving flavor of foodstuffs and so forth. While the proteolysis method, semi-synthetic method and so forth are known as methods for producing cysteine, mainly used methods at present are the proteolysis method and the semi-synthetic method. In order to utilize cysteine for improving flavor of foodstuffs, natural food materials having a high cysteine content are desired. However, such natural food materials have hardly been known so far. Glutathione, which is a tripeptide consisting of cysteine bonded with glutamic acid and glycine, is also known to be used for improving flavor of foodstuffs. Glutathione is synthesized from cysteine via.gamma.-glutamylcysteine. However,.gamma.-glutamylcysteine is scarcely used for improving flavor of foodstuffs. Web site: http://appft1.uspto.gov/netahtml/PTO/search-bool.html •
Method of determining a chemotherapeutic regimen based on glutathione-Stransferase pi expression Inventor(s): Danenberg, Kathleen D.; (Altadena, CA) Correspondence: Kenyon & Kenyon; 1500 K Street, N.W., Suite 700; Washington; DC; 20005; US Patent Application Number: 20020197609 Date filed: June 14, 2001 Abstract: The present invention relates to prognostic methods which are useful in medicine, particularly cancer chemotherapy. The object of the invention to provide a method for assessing GST-pi expression levels in fixed or fixed and paraffin embedded tissues and prognosticate the probable resistance or sensitivity of a patient's tumor to treatment with platinum-based therapies by examination of the amount of GST-pi mRNA in a patient's tumor cells and comparing it to a predetermined threshold expression level. More specifically, the invention provides to oligonucleotide primer pair GST-piand methods comprising their use for detecting levels of GST-pi mRNA. Excerpt(s): The present invention relates to prognostic methods which are useful in medicine, particularly cancer chemotherapy. More particularly, the invention relates to assessment of tumor cell gene expression in a patient. The resistance of tumor cells to chemotherapeutic agents that target DNA, especially agents that damage DNA in the manner of platinating agents is assayed by examining the mRNA expressed from genes involved in DNA repair in humans. Cancer arises when a normal cell undergoes neoplastic transformation and becomes a malignant cell. Transformed (malignant) cells escape normal physiologic controls specifying cell phenotype and restraining cell proliferation. Transformed cells in an individual's body thus proliferate, forming a tumor. When a tumor is found, the clinical objective is to destroy malignant cells selectively while mitigating any harm caused to normal cells in the individual undergoing treatment. Chemotherapy is based on the use of drugs that are selectively toxic (cytotoxic) to cancer cells. Several general classes of chemotherapeutic drugs have been developed, including drugs that interfere with nucleic acid synthesis, protein synthesis, and other vital metabolic processes. These generally are referred to as antimetabolite drugs. Other classes of chemotherapeutic drugs inflict damage on cellular DNA. Drugs of these classes generally are referred to as genotoxic. Susceptibility of an individual neoplasm to a desired chemotherapeutic drug or combination of drugs often, however, can be accurately assessed only after a trial period
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of treatment. The time invested in an unsuccessful trial period poses a significant risk in the clinical management of aggressive malignancies. Web site: http://appft1.uspto.gov/netahtml/PTO/search-bool.html •
Method of increasing the presence of glutathione in cells Inventor(s): Hageman, Robert Johan Joseph; (Waddinxveen, NL), Norren, Klaske van; (Renkum, NL), Smit, Hobbe Friso; (Utrecht, NL) Correspondence: Bacon & Thomas, Pllc; 625 Slaters Lane; Fourth Floor; Alexandria; VA; 22314 Patent Application Number: 20030054048 Date filed: October 31, 2002 Abstract: A composition for increasing the presence of glutathione in cells and for treating or preventing impaired liver function. The composition includes a precursor of gluthathione, and enhancer of glutathione biosynthesis, and a third component which is a lignan or the third component is a combination of an enhancer of gluthathione regeneration and an enhancer of glutathione-mediated conjugation. The precursor of gluthathione is cysteine or is a functional equivalent of cysteine which yields cysteine when administered to a mammal undergoing treatment. Excerpt(s): This invention relates to a method of increasing the presence of glutathione in cells including treating or preventing of impaired liver function by administering to a mammal in the need thereof a dietetic or pharmaceutical composition and to a corresponding dietetic or pharmaceutical composition. The liver is the major organ involved in metabolism of protein, carbohydrates, and fats, but is also the major organ for detoxification. Potential toxic compounds are converted into inactive metabolites by phase I-metabolising enzymes and excreted. Alternatively, metabolites are further conjugated by phase II-metabolising enzymes and excreted after all. Both hepatitis C and the exposure to liver toxins can lead to hepatocarcinoma, possibly via the same mechanism of incompetence of the liver to respond to toxins, either endo-toxins or exotoxins. Web site: http://appft1.uspto.gov/netahtml/PTO/search-bool.html
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Method of treating environmental stress Inventor(s): Egawa, Mariko; (Yokohama-Shi, JP), Kohno, Yoshiyuki; (Yokohama-Shi, JP), Sakamoto, Tetsuo; (Yokohama-Shi, JP) Correspondence: Law Offices OF Townsend & Banta; Suite 500, #50028; 1225 Eye Street, N.W.; Washington; DC; 20005; US Patent Application Number: 20030073639 Date filed: November 7, 2002 Abstract: There is provided a method of treating environmental stress due to the adverse effects of tobacco smoke and automobile exhaust gases. The method of treatment comprises applying to the skin a liniment composition containing one or more ingredients selected from among a group consisting of sulfur containing amino acids, metabolic intermediates of sulfur containing amino acids, tannin and vitamin C and its derivatives. A preferred sulfur containing amino acid is glutathione and preferred
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metabolic intermediates of sulfur containing amino acids are thiotaurine or hypotaurine. Also, hydroxycarboxylic acid or its derivatives can advantageously be added to this liniment composition to treat environmental stress. Excerpt(s): This application is a continuation in part of U.S. application Ser. No. 09/147,293, filed Nov. 23, 1998, now abandoned, which is incorporated herein by reference. The present invention relates in general to the treatment of environmental stress and, more particularly, to a method of treating various adverse effects on the skin caused by external environmental stress due to contact of the skin with tobacco smoke and/or automobile exhaust emissions. In modern society, people are frequently exposed to floating fine particles. Web site: http://appft1.uspto.gov/netahtml/PTO/search-bool.html •
Methods and compositions for the treatment of human and animal cancers Inventor(s): Kiss, Zoltan; (Austin, MN) Correspondence: Paul W. Busse; Faegre & Benson Llp; 2200 Wells Fargo Center; 90 South Seventh Street; Minneapolis; MN; 55402-3901; US Patent Application Number: 20020177583 Date filed: May 24, 2001 Abstract: Methods and compositions for altering the viability of cells, particularly cancers in animals and humans are disclosed. The compositions of the present invention are formed from a set of components comprising one or more of the following: a dithiocarbonyl, preferably dithiocarbamate, compound; a divalent metal ion; a modulator of cellular glutathione levels; and an inhibitor of the phosphorylation of choline. The compositions described herein induce a relatively selective and rapid effect on the viability of cancer cells by inducing a mixture of apoptotic and necrotic cell death, with the dominant pathway being apoptosis. Particularly preferred active compositions comprise all four components, although combinations of fewer components can be fully effective in certain tumors. Excerpt(s): This application claims priority to U.S. Provisional Application entitled METHODS AND COMPOSITIONS FOR THE TREATMENT OF HUMAN AND ANIMAL CANCERS, filed on Mar. 29, 2001, Serial No. ______ (Attorney Docket No. 54938-226916). This invention relates to methods and compositions for altering the viability of cells, particularly normormal or nonhealthy cells, such as those comprising various cancers in animals and humans. More particularly, the invention relates to the preparation and use of the compositions of the present invention to rapidly kill or weaken cancerous cells within or on the surface of an animal or human body. The invention also relates to methods to minimize metastatic growth potential of cancer cells derived from primary tumors during surgical intervention. Primarily intratumoral, but also systemic or parenteral treatments as well as pre-operative, post-operative, or topical treatment of cancers are contemplated. The present invention illustrates surprising and rapid effectiveness and relative specificity against a broad class of cancer cells and cancerous tissues over healthy cells. Despite vast advances in screening, lifestyle moderation, and therapeutic approaches, cancer continues to be one of the leading causes of death in the world. Drug toxicity, drug resistance, and the varying genetic backgrounds of different cancer sub-types have complicated the development of chemotherapeutics that are specifically cytotoxic to cancerous cells, yet minimally toxic to the patient.
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Web site: http://appft1.uspto.gov/netahtml/PTO/search-bool.html •
Methods and products for bad breath Inventor(s): Zielinski, Jan; (Vista, CA) Correspondence: Robert D. Fish; Rutan & Tucker, Llp; P.O. Box 1950; 611 Anton BLVD., 14th Floor; Costa Mesa; CA; 92628-1950; US Patent Application Number: 20030124230 Date filed: December 4, 2002 Abstract: A food product includes at least silymarin, betaine, or a combination thereof, and one of an antioxidant, glutathione, a methyl group donor, a sulfur group donor, acetyl CoA, or glucuronic acid in an amount effective to significantly reduce bad breath. Especially preferred food products include significant quantities of silymarin and betaine. The food product is advantageously advertised as reducing bad breath, improving liver function, digestion, and/or periodontal health. Contemplated food products include animal treats, and especially dog biscuits or other treats. Excerpt(s): This application claims the benefit of International application PCT/US01/17863, which was filed Jun. 1, 2001 and of U.S. provisional application 60/366378, which was filed on Mar. 20, 2002, which is incorporated by reference herein. The field of the invention is food products and related methods. Bad breath is unfortunately relatively common among humans and animals, and may be caused by various factors including certain types of food, inability to properly digest, and periodontal diseases. Web site: http://appft1.uspto.gov/netahtml/PTO/search-bool.html
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Methods for preventing and treating loss of balance function due to oxidative stress Inventor(s): Kopke, Richard D.; (San Diego, CA) Correspondence: Counsel For Intellectual Property; Naval Medical Research Center; 503 Robert Grant Avenue; Silver Spring; MD; 20910-7500; US Patent Application Number: 20030191064 Date filed: March 31, 2003 Abstract: The present invention provides methods for preventing and treating loss of, or impairments to, the sense of balance. Specifically, the invention provides methods for preserving the sensory hair cells and neurons of the inner ear vestibular apparatus by preventing or reducing the damaging effects of oxidative stress by administering an effective amount of the following therapeutic agents: antioxidants; compounds utilized by inner ear cells for synthesis of glutathione; antioxidant enzyme inducers; trophic factors; mitochondrial biogenesis factors; and combinations thereof. Excerpt(s): This application is a continuation-in-part application of U.S. application Ser. No. 09/766,625 filed Jan. 23, 2001 (the entirety of which is incorporated herein by reference for all purposes) which claims benefit of Non-Provisional application Ser. No. 09/126,707, now U.S. Pat. No. 6,177,434 filed Jul. 31, 1998 (the entirety of which is incorporated herein by reference for all purposes) which claims benefit of provisional application No. 60/069,761 filed Dec. 16, 1997 (the entirety of which is incorporated herein by reference for all purposes). The present invention relates generally to methods
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and composition for preventing and treating loss of, or impairments to, the sense of balance. More specifically, the invention provides methods and composition for preserving the sensory hair cells and neurons of the inner ear vestibular apparatus by preventing or reducing the damaging effects of oxidative stress by administering an effective amount of certain therapeutic agents to a subject at risk for or experiencing loss of balance or injury to the inner ear balance organ. Balance dysfunction is a common disorder affecting as many as 40 million people in the United States per year. Dizziness is one of the most frequent complaints causing a patient to seek medical care (See Palaniappan R., Balance Disorders in Adults: An Overview, Hosp. Med. Vol., (2002) 63(5):278-81). Balance problems are a frequent cause of falls among the elderly and such falls are a common cause of death in this population (See Bloem B., Steijns J., and SmitsEngelsman B., An Update on Falls, Curr. Opin. in Neurol., (2003) 16(1):15-26). At this time, medical treatment for balance disorders consists of supportive therapy, treatment of symptoms, and surgical or medical ablation of the injured ear where dizziness symptoms are relieved by cutting the balance nerve or completely destroying the balance tissue. Currently, there is no clinically proven medical approach for balance disorders that is aimed at preventing or reversing injury to the inner ear balance system (See Brandt T., Management of Vestibular Disorders, J. Neurol. (2000) 247(7):491-9). Web site: http://appft1.uspto.gov/netahtml/PTO/search-bool.html •
Methods for treating hearing loss Inventor(s): Kil, Jonathan; (Seattle, WA), Lynch, Eric D.; (Lake Forest Park, WA) Correspondence: Christensen, O'connor, Johnson, Kindness, Pllc; 1420 Fifth Avenue; Suite 2800; Seattle; WA; 98101-2347; US Patent Application Number: 20030162747 Date filed: January 3, 2003 Abstract: In one aspect, the present invention provides otoprotectant compositions useful for ameliorating hearing loss. In some embodiments, the otoprotective compositions comprise at least one glutathione peroxidase mimic. In some embodiments, the otoprotective compositions comprise at least one glutathione peroxidase mimic and at least one otoprotectant selected from the group consisting of a xanthine oxidase inhibitor and a glutathione or glutathione precursor. In some embodiments, the otoprotective compositions comprise at least one glutathione peroxidase mimic, at least one xanthine oxidase inhibitor, at least one glutathione or glutathione precursor. In another aspect, the present invention provides methods for ameliorating hearing loss by administering to a subject an amount of an otoprotective composition that is effective to ameliorate hearing loss. Excerpt(s): This application claims the benefit of U.S. Provisional Application No. 60/345,813, filed Jan. 4, 2002, under 35 U.S.C.sctn.119. The present invention relates to methods and compositions for treating and preventing hearing loss. A major cause of acquired hearing loss is loud noise. Exposure to harmful noise levels is common in the workplace. The National Institute for Occupational Safety and Health estimates that about 30 million workers in the United States encounter hazardous levels of noise. (Franks et al. (1996) Preventing Occupational Hearing Loss--A Practical Guide, DHHA (NIOSH) Publication No. 96-110, p.1). These levels are encountered in, for example, construction, mining, agriculture, manufacturing and utilities, transportation, and in the military. The incidence of noise associated hearing loss continues to increase in spite of
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efforts to regulate job related noise exposure, and to improve the use of hearing protective devices such as ear muffs and ear plugs. Web site: http://appft1.uspto.gov/netahtml/PTO/search-bool.html •
Multiplex protein interaction determinations using glutathione-GST binding Inventor(s): Nguyen, Quan; (Pleasant Hill, CA), Song, Yong; (San Pablo, CA) Correspondence: Townsend And Townsend And Crew, Llp; Two Embarcadero Center; Eighth Floor; San Francisco; CA; 94111-3834; US Patent Application Number: 20030013116 Date filed: September 13, 2002 Abstract: Fusion proteins in which glutathione S-transferase (GST) is a fusion partner are used as an immobilized binding member in screening procedures or other multianalyte test procedures based on protein interaction. In such procedures, a particular protein is selected from a group of candidate proteins on the basis of the binding affinity of that protein for a target protein, with either the candidate proteins or the target protein being a fusion partner with GST and the GST portion of the fusion partner having been immobilized on glutathione-coated particles by the binding of GST to glutathione. The particles themselves are classifiable by different values of a differentiation parameter that permits them to be distinguished by flow cytometry, and the procedure is conducted in a manner that associates the individual candidate proteins with individual classes of the particles. When a binding interaction occurs between a candidate protein and the target protein, the particles on which the interaction has occurred are readily distinguished by flow cytometry and correlated with the candidate protein that exhibited the binding. Excerpt(s): This invention resides in the field of screening assays to assess proteinprotein interactions, and to screen candidate proteins for their affinity to target proteins. Many clinical and research investigations involve the study of protein-protein interactions for purposes such as screening proteins or peptides to find those that display binding specificity to a particular protein, determining the binding affinity of two interacting proteins, and identifying the site or amino acid of a protein that is responsible for the interaction between that protein and a second protein. Information relevant to the function of a protein can be obtained by determining whether and how that protein interacts with another protein of known function. This type of information is also of value in the design and screening of drugs, and generally in developing methods for the diagnosis and treatment of diseases. Of further relevance to this invention is the known specific binding interaction between glutathione and glutathione S-transferase. Glutathione (.gamma.-glutamylcysteinylglycine) is a triamino acid peptide that is found in the cells of higher animals at a concentration of approximately 5 mM. A characteristic feature of glutathione is its linkage at the.gamma.-carboxyl group rather than the.alpha.-carboxyl group of the glutamyl residue. Glutathione S-transferase ("GST") is a 26-kDa protein with a very high affinity for glutathione. Use has been made of this affinity in the purification or proteins, by first forming a recombinant protein in which GST is included as a fusion partner and then purifying the recombinant protein by affinity chromatography on immobilized glutathione columns. GST-containing recombinant proteins have also been used as a means of detecting antibodies to the protein that is fused to GST. These methods are described for example by Murray, A. M., et al., "Production of glutathione-coated
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microtitre plates for capturing recombinant glutathione S-transferase fusion proteins as antigens in immunoassays," J. Immunol. Meth. 218 (1998): 133-139. Web site: http://appft1.uspto.gov/netahtml/PTO/search-bool.html •
N-acetylcysteine compositions and methods for the treatment and prevention of drug toxicity Inventor(s): Andrus, James; (Redwood City, CA), De Rosa, Stephen C.; (Bethesda, MD), Herzenberg, Leonard A.; (Stanford, CA), Herzenberg, Leonore A.; (Stanford, CA) Correspondence: Greenberg Traurig, Llp; 885 Third Avenue; New York; NY; 10022; US Patent Application Number: 20030069311 Date filed: November 4, 2002 Abstract: The invention provides pharmaceutical compositions for the treatment or prevention of the toxic effects of therapeutic agents and methods of treating or preventing such toxicity using a toxicity reducing amount of N-acetylcysteine either alone or in combination with a therapeutically effective amount or, to achieve its therapeutic advantages, an amount larger than what is customarily given as a therapeutically effective amount, of a therapeutic agent. The invention also provides pharmaceutical compositions for the treatment or prevention of the toxic effects of therapeutic agents and methods of treating or preventing such toxicity using a toxicity reducing amount of N-acetylcysteine either alone or in combination with a therapeutically effective amount or, to achieve its therapeutic advantages, an amount larger than what is customarily given as a therapeutically effective amount, of a therapeutic agent whose side effects are made worse by increased oxidative stress or treatment related decreases in subject cysteine/glutathione levels or are otherwise relieved by administration of NAC. Excerpt(s): This application is a division of copending application 09/833,228 filed Apr. 11, 2001 and provisional application 60/280,600, filed Mar. 30, 2001. The present invention relates to compositions for the treatment or prevention of drug toxicity in mammals including humans which may result from the administration of therapeutic agents and to methods of treating or preventing such toxicity. The compositions of this invention comprise a toxicity-reducing amount of N-acetylcysteine (NAC) alone or in combination with a therapeutically effective amount or, to achieve its therapeutic advantages, an amount larger than what is customarily given as a therapeutically effective amount, of a therapeutic agent, preferably in combination with a pharmaceutically acceptable carrier. The method of treating or preventing drug toxicity in humans comprises administering a toxicity-reducing amount of NAC alone or in combination with a therapeutically effective amount or, to achieve its therapeutic advantages, an amount larger than what is customarily given as a therapeutically effective amount, of a therapeutic agent, preferably in combination with a pharmaceutically acceptable carrier. Glutathione (GSH), a tripeptide that is normally found in all animal cells and most plants and bacteria at relatively high (1-10 millimolar) concentrations, helps to protect cells against oxidative damage that would otherwise be caused by free radicals and reactive oxidative intermediates (ROIs) produced during cell metabolism or as the results of, for example, drug overdose. Glutathione is itself the major scavenger of reactive oxidative intermediates present in all eukaryotic forms of life and is generally required to protect cells against damage by oxidants. Glutathione reduces (and thereby detoxifies) intracellular oxidants and is consumed by this reaction. Glutathione is oxidized to the disulfide linked dimer (GSSG), which is actively pumped
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out of cells and becomes largely unavailable for reconversion to reduced glutathione. Thus, unless glutathione is resynthesized through other pathways, utilization of this compound is associated with a reduction in the amount of glutathione available. The antioxidant effects of glutathione are also mediated less directly by the role of this compound in maintaining other antioxidants in reduced form. Thus, pharmaceutical compounds that replenish or elevate glutathione levels work, at least in part, through enhancement of the defense mechanisms seemingly utilized to normally protect tissue from ROI mediated damage. Web site: http://appft1.uspto.gov/netahtml/PTO/search-bool.html •
Nck SH3 binding peptides Inventor(s): Der, Channing J.; (Chapel Hill, NC), Fowlkes, Dana M.; (Chapel Hill, NC), Kay, Brian K.; (Chapel Hill, NC), Quilliam, Lawrence A.; (Indianapolis, IN), Rider, James E.; (Carrboro, NC), Sparks, Andrew B.; (Pikesville, MD), Thorn, Judith M.; (Carrboro, NC) Correspondence: Morgan & Finnegan, L.L.P.; 345 Park Avenue; New York; NY; 101540053; US Patent Application Number: 20030186863 Date filed: May 31, 2002 Abstract: Peptides having general and specific binding affinities for the Src homology region 3 (SH3) domains of proteins are disclosed in the present invention. In particular, SH3 binding peptides have been isolated from phage-displayed random peptide libraries which had been screened for isolates that bind to bacterial fusion proteins comprising SH3 and glutathione S-transferase (GST). Preferred peptides are disclosed which comprise a core 7-mer sequence (preferably, a consensus motif) and two or more, preferably at least six, additional amino acid residues flanking the core sequence, for a total length of 9, preferably at least 13, amino acid residues and no more than about 45 amino acid residues. Such peptides manifest preferential binding affinities for certain SH3 domains. The preferred peptides exhibit specific binding affinities for the Srcfamily of proteins. In vitro and in vivo results are presented which demonstrate the biochemical activity of such peptides. Excerpt(s): This application is a continuation-in-part of co-pending U.S. patent application Ser. No. 08/483,555 filed Jun. 7, 1995 which in turn is a continuation-in-part of U.S. patent application Ser. No. 08/278,865 filed Jul. 22, 1994, the entire contents of each of which are incorporated herein by reference. The present invention relates to SH3 binding peptides having a broad range of binding specificities. That is, certain members of the SH3 binding peptides disclosed bind with approximately the same facility with SH3 domains derived from different SH3 domain-containing proteins. Other members, in contrast, bind with a much greater degree of affinity for specific SH3 domains. The SH3 binding peptides are obtained from random peptide libraries that are also phagedisplayed. Methods are described of obtaining the phage clones that bind to the SH3 domain targets and of determining their relevant nucleotide sequences and consequent primary amino acid sequence of the binding peptides. The resulting SH3 binding proteins are useful in a number of ways, including, but not limited to, providing a method of modulating signal transduction pathways at the cellular level, of modulating oncogenic protein activity or of providing lead compounds for development of drugs with the ability to modulate broad classes, as well as specific classes, of proteins involved in signal transduction. Among a number of proteins involved in eukaryotic cell
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signaling, there is a common sequence motif called the SH3 domain. It is 50-70 amino acids in length, moderately conserved in primary structure, and can be present from one to several times in a large number of proteins involved in signal transduction and in cytoskeletal proteins. Web site: http://appft1.uspto.gov/netahtml/PTO/search-bool.html •
Novel prodrugs of N-H bond-containing compounds and methods of making thereof Inventor(s): Guarino, Victor R.; (Lawrence, KS), Karunaratne, Veranja; (Lawrence, KS), Stella, Valentino J.; (Lawrence, KS) Correspondence: Jean M. Dickman; Shook, Hardy & Bacon L.L.P.; 1200 Main Street; Kansas City; MO; 64105-2118; US Patent Application Number: 20030119814 Date filed: October 16, 2002 Excerpt(s): This application claims the benefit of priority to Provisional Application No. 60/329,868 filed on Oct. 16, 2001. The present invention relates to novel prodrugs of pharmaceutical compounds containing one or more N--H bonds. More specifically, the present embodiment of the invention relates to prodrugs wherein sulfur-containing promoieties are attached to pharmaceutical compounds which contain one or more N-H bonds to produce prodrugs containing at least one N--S bond. These N--S bondcontaining prodrugs could have optimized stability, solubility, cell membrane permeability, pharmacokinetic properties and other pharmaceutical properties over the pharmaceutical compounds from which they are formed, depending upon the nature of the promoiety. Reversion of the prodrug to the parent pharmaceutical compound occurs by the reaction of the prodrugs with thiol molecules such as cysteine, glutathione or any other thiol containing molecule. Further, the present invention relates to methods of making N--S bond-containing prodrugs of pharmaceutical compounds containing one or more N--H bonds whereby sulfur-containing promoieties are attached to the parent compounds to create at least one N--S bond. To date, there does not appear to be any known art using technology to create N--S bond-containing prodrugs. However, Bridges studied the inactivation of toxin and carcinogen, N-trichloromethylthio-4-cyclohexane 1,2-dicarboximide or alternatively N-(trichloromethylthio)-3a,4,7,7a-tetrahydrophthalimide ("Captan"), a fungicide used for agricultural purposes and in paints, soaps, paper and leather. Captan has very low solubility and an N--S bond. Captan was administered to rabbits and the levels of Captan were tested. The study found that Captan, in its active form, was broken down in the body due to high thiols in the blood. Thus, this resulted in the rapid inactivation of Captan, thus, lowering the biological and genetic damage caused to a mammalian body by Captan. Bridges, B. A., The Mutagency of Captan and Related Fungicides. Mutation Research, 1975 32: p. 3-34. Web site: http://appft1.uspto.gov/netahtml/PTO/search-bool.html
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Nutritional or therapeutic supplement and method Inventor(s): Crum, Albert; (Brooklyn Heights, NY) Correspondence: Klauber & Jackson; 411 Hackensack Avenue; Hackensack; NJ; 07601 Patent Application Number: 20030124198 Date filed: September 23, 2002
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Abstract: Nutritional compositions containing selenium, colostrum and whey are described. The compositions may be mixed with mammalian food to increase the concentration of glutathione in the mammalian body thereby to enhance the response of the mammal's immune system to infection. Excerpt(s): This application is a continuation-in-part of copending and commonly owned application Ser. No. 10/085,994 filed Sep. 26, 2001 which is a continuation of application Ser. No. 09/371,812 filed Aug. 11, 1999, now abandoned, which application is a continuation-in-part of application Ser. No. 09/095,383 filed Jun. 10, 1998 now abandoned, all of which applications are herein specifically incorporated by reference in their entireties. The present invention provides novel therapeutic nutritive compositions useful for increasing glutathione production in mammals, including humans, thereby to enhance the mammalian response to infection, stress or other trauma. More specifically, the invention provides novel food supplement compositions containing as the essential ingredients colostrum, a selected whey product and defined amounts of selenium or an organic or inorganic, water soluble selenium precursor. There are at the present time hundreds, perhaps thousands of food supplement compositions. Most of these compositions are designed to enhance the nutritional value of the food consumed by mammals including humans and animals, to increase energy levels, or to maintain electrolyte balance. These food supplements often comprise mixtures which if administered orally or parenterally are intended to bring to desired values the amount of vitamins, minerals, amino acids, salts and other materials required for proper nutrition in mammals. They are particularly valuable as sources of essential amino acids which may or may not be in foods but, in any event are destroyed or not synthesized by the metabolic processes of the mammalian body. Eight such amino acids are known. These include for example, leucine, isoleucine and phenylalanine. Web site: http://appft1.uspto.gov/netahtml/PTO/search-bool.html •
Plant drug for treatment of liver disease Inventor(s): Zhao, Xinxian; (Shenzhen, CN) Correspondence: Xinxian Zhao; 67-08 168th Street; Flushing; NY; 11365; US Patent Application Number: 20030026854 Date filed: April 4, 2001 Abstract: The present invention related to safe plant drug for treatment of liver disease, specifically, this invention proves a safe plant drug Schisandrin and its preparation. Schisandrin has the following pharmaceutical functions: increasing tumor suppresson genes express activity, decreasing activity of oncogenes, increasing immune function, increasing liver DNA synthesis, decreasing serum alamine aminotransferase activity, increasing glutathione level, increasing glutathione reductase activity, decreasing lipid peroxidation of liver, increasing hepatic microsomal monooxygenases activity, increasing ATP content in liver, increasing energy metabolism activity, decreasing density lipoprotein oxidation, protecting gastrointestinal function, increasing killer cell activity, increasing complement activity, decreasing induced liver cancer activity and decreasing grown of cancer cells. Excerpt(s): The present invention related to safe plant drug for treatment of liver disease, specifically, this invention proves a safe plant drug Schisandrin and its preparation. The most common types of liver disease are hepatitis and cirrhosis. So far, no one drug has been succeeded to treat for hepatitis and cirrhosis. The hepatitis victim
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is always short on appetite and finds it is difficult. Therefore, it is important that to eat the suitable food to supply liver for self-repair. The traditional medical book described that a good treatment for hepatitis is high protein diet, Brewer's yeast, wheat germ, egg yolks, and other high quality protein, which combats the stress damage. Some drugs have been used for treatment of liver disease, but clinical results are not successful. For the reasons given above, to discover an effect safe drug for treating patients with liver disease is necessary and important. Web site: http://appft1.uspto.gov/netahtml/PTO/search-bool.html •
Polyglycerol and lactose compositions for the protection of living systems from states of reduced metabolism Inventor(s): Fahy, Greg; (Corona, CA), Wu, Jun; (Rancho Cucamonga, CA) Correspondence: Knobbe Martens Olson & Bear Llp; 2040 Main Street; Fourteenth Floor; Irvine; CA; 91614; US Patent Application Number: 20030027924 Date filed: February 1, 2002 Abstract: Polyglycerol, lactose, and a combination of polyglycerol and lactose are effective at preserving cells, tissues, and organs from damage due to hypothermic, ischemic, or other metabolic impairment, and a mixture of polyglycerol plus lactose is particularly useful for the hypothermic storage of cells, tissues, and organs. The mixture of polyglycerol and lactose can be further improved by the addition of chondroitin sulfate, chlorpromazine, calcium, citrate, glutathione, adenine, glucose, magnesium, and a pH buffer. Excerpt(s): This application is a Continuation in Part of U.S. patent application Ser. No. 09/726,857, filed Nov. 30, 2000 which claims priority under 35 U.S.C.sctn.119 of U.S. Provisional Application No. 60/167,963, filed Nov. 30, 1999 (herein incorporated by reference). This application is also a Continuation in Part of U.S. patent Application Ser. No. 09/916,396, filed Jul. 27, 2001, which claims priority under 35 U.S.C.sctn.119 of U.S. Provisional application 60/221,691, filed Jul. 31, 2000, all of which are herein incorporated by reference. This invention relates generally to the field of cell, tissue, and organ preservation. More specifically, this invention relates to the field of protection of cells, tissues, and organs from states such as hypothermia. Still more specifically, this invention relates to the use of polyglycerol and other solutes, especially alpha lactose, for protecting living systems during periods of depressed metabolism, with or without supercooling. The current shortage of organs for transplantation mandates that maximum usage be obtained from the scarce resource represented by vital organs. Despite this imperative, many organs that could be transplanted are not transplanted due to limitations on the useful lifetime of organs after they are removed from the body. Thus, there is clearly a need for better preservation solutions for vital organs. Web site: http://appft1.uspto.gov/netahtml/PTO/search-bool.html
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Process for producing cysteinylglycine-enriched food material and process for producing flavor-enhancing agent Inventor(s): Kato, Yuji; (Kanagawa, JP), Kohmura, Masanori; (Kanagawa, JP), Nishimura, Yasushi; (Kawasaki-shi, Kanagawa, JP), Ueda, Yoichi; (Kanagawa, JP) Correspondence: Oblon, Spivak, Mcclelland, Maier & Neustadt, P.C.; 1940 Duke Street; Alexandria; VA; 22314; US Patent Application Number: 20030138521 Date filed: January 2, 2003 Abstract: Disclosed in this application are a method for producing a food material containing cysteinylglycine at a high content, which comprises the step of (a) maintaining a starting food material containing glutathione in a ratio of 1% by weight or more based on the solid content at a temperature of 50 to 120.degree. C. and a pH of 1 to 7 in the presence of water, or (b) treating the food material with a.gamma.glutamylpeptide hydrolase at a temperature of 15 to 70.degree. C. and a pH of 3 to 9 in the presence of water, whereby a food material rich in cysteinylglycine is allowed to result, as well as a method for producing a food flavor (or savor) enhancer, which comprises the steps of (a) adding a sugar to cysteinylglycine or a food material containing cysteinylglycine in a ratio of 0.5% by weight or more based on the solid content, and (b) heating the resulting mixture at a temperature of 70 to 180.degree. C. for a period of 10 to 180 minutes in the presence of water, whereby a natural food material containing crysteinylglycine at a high content, and therefore, a food savor enhancer rich in cysteinylglycine, can be easily provided. Excerpt(s): The present invention relates to a food material containing cysteinylglycine at a high content, and to a food flavor enhancer, i.e., a food savor enhancer. In greater detail, it relates to a method for producing a food material containing cysteinylglycine at a high content, which comprises the step of (a) maintaining a starting food material containing glutathione in a ratio of 1% by weight or more based on the solid content at a temperature of 50 to 120.degree. C. and a pH of 1 to 7 in the presence of water, or (b) treating the food material with a.gamma.-glutamylpeptide hydrolase at a temperature of 15 to 70.degree. C. and a pH of 3 to 9 in the presence of water, whereby a food material rich in cysteinylglycine is allowed to result, and to a method for producing a food flavor enhancer, which comprises the steps of (a) adding a sugar to cysteinylglycine or a food material containing cysteinylglycine in a ratio of 0.5% by weight or more based on the solid content, and (b) heating the resulting mixture at a temperature of 70 to 180.degree. C. for a period of 10 to 180 minutes in the presence of water. Incidentally, in the present specification, the term "glutathione" includes the oxidized form (in the broad sense), and the term "cysteinylglycine" also includes the oxidized form (in the broad sense), unless otherwise construed in the context. Recently, the demand for processed foods having a meat-like flavor has been increased with westernization and diversification of the eating habits in Japan. Particularly, in the production of soups, processed meat products such as ham, sausage and the like, and cooked foods such as hamburger and the like, there is an increasing demand for good tasting and inexpensive meat flavor. Web site: http://appft1.uspto.gov/netahtml/PTO/search-bool.html
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Skin treatment Inventor(s): Steenbergen, Mark van; (Temse, BE) Correspondence: Caesar, Rivise, Bernstein,; Cohen & Pokotilow, LTD.; 12th Floor, Seven Penn Center; 1635 Market Street; Philadelphia; PA; 19103-2212; US Patent Application Number: 20030072827 Date filed: September 30, 2002 Abstract: A composition for application to the skin to remove the wrinkles characteristic of a smoker, comprises the combination of an anti-ageing component, an anti-stress component and anti-oxidant. Preferably the anti-ageing agent is a mixture of plant extracts such as walnut and beech. The anti-stress component may be a vitamin. The anti-oxidant component may be a stimulant for the glutathione system, preferably presented in micro-encapsulated form. Excerpt(s): The invention relates to a composition for use in treating skin, especially that of smokers. It has been realised that smoking has an effect on the skin, in particular it causes the formation of wrinkles and the like. It has been realised that tobacco smoke extract will induce zinc-dependant proteases which degrade dermal collagen and other extracellular matrix molecules. Tobacco smoking also lowers the level of oestrogen in the blood. The nitrogen gases from cigarettes generate carcinogenic nitrosamines in the body tissues. Cigarette smoke is a potentially free radical generator. It is a combination of these factors which cause the skin to become dry and age prematurely in the case of tobacco smokers, especially nicotine addicts. These effects can persist for a period even if the smoker gives up smoking. There is no skin composition available specifically adapted for treating the skin of smokers. It is one object of this invention to provide a skin treatment composition intended to improve the appearance of smokers, both male and female. According to the invention in one aspect there is provided a skin treatment composition comprising in combination an anti-ageing component, an anti-stress component and an anti-oxidant component. Web site: http://appft1.uspto.gov/netahtml/PTO/search-bool.html
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Stabilized bioactive peptides and methods of identification, synthesis, and use Inventor(s): Altman, Elliot; (Athens, GA) Correspondence: Fish & Richardson P.C.; 3300 Dain Rascher Plaza; 60 South Sixth Street; Minneapolis; MN; 55402; US Patent Application Number: 20030190740 Date filed: July 31, 2002 Abstract: An intracellular selection system allows screening for peptide bioactivity and stability. Randomized recombinant peptides are screened for bioactivity in a tightly regulated expression system, preferably derived from the wild-type lac operon. Bioactive peptides thus identified are inherently protease- and peptidase-resistant. Also provided are bioactive peptides stabilized by a stabilizing group at the N-terminus, the C-terminus, or both. The stabilizing group can be a small stable protein, such as the Rop protein, glutathione sulfotransferase, thioredoxin, maltose binding protein, or glutathione reductase, an.alpha.-helical moiety, or one or more proline residues. Excerpt(s): This application is a continuation-in-part of U.S. Ser. No. 09/701,947, filed Dec. 5, 2000, which is a National Stage application under 35 U.S.C.sctn.371 of
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PCT/US99/23731, filed Oct. 12, 1999, which in turn claims the benefit of U.S. Provisional Patent Applications Serial Nos. 60/104,013, filed Oct. 13, 1998, and 60/112,150, filed Dec. 14, 1998, each of which is incorporated herein by reference in its entirety. This invention relates to stabilized bioactive peptides, and more particularly to bioactive peptides that contain heterologous stabilizing groups attached to one or both of the bioactive peptide's termini. Bioactive peptides are small peptides that elicit a biological activity. Since the discovery of secretin in 1902, over 500 of these peptides which average 20 amino acids in size have been identified and characterized. They have been isolated from a variety of systems, exhibit a wide range of actions, and have been utilized as therapeutic agents in the field of medicine and as diagnostic tools in both basic and applied research. Tables 1 and 2 list some of the best known bioactive peptides. Web site: http://appft1.uspto.gov/netahtml/PTO/search-bool.html •
TARGETED DRUG DELIVERY USING SULFONAMIDE DERIVATIVES Inventor(s): KOEPLINGER, KENNETH A.; (PORTAGE, MI), PETERSON, TILLIE; (PORTAGE, MI), TOMASSELLI, ALFREDO G.; (KALAMAZOO, MI), ZHAO, ZHIYANG; (WESTERLY, RI) Correspondence: Arent Fox Kintner & Kahn, Pllc; 1050 Connecticut AVE. NW; Suite 600; Washington; DC; 20036-5339; US Patent Application Number: 20030109555 Date filed: March 17, 1999 Excerpt(s): The present invention relates to Glutathione S-transferase (GST)/Reduced Glutathione (GSH) as a means for the in-vivo release of a drug that has been conjugated to specific electrophilic moieties via a sulfonamide bond. The drug may be an anticancer agent (or one with other therapeutic properties) carrying a free --NH-- which has been derivatized by the attachment of an electrophile containing a moiety, such as p-CN-- or p-NO.sub.2-pyridinylsulfonyl groups, or p-NO.sub.2- or 2,4 dinitrophenylsulfonyl groups, or suitable derivatives thereof, to make a prodrug. The purpose of such a modification is to protect the free amino group, or to increase the drug solubility or alter absorption or distribution, or to improve some other physical, chemical, and pharmacological properties. Inside cells the prodrug is recognized and bound by GST which catalyses sulfonamide cleavage to release the active drug. Optionally, the sulfonamide moiety may have a targeting molecule attached to it. The present invention also provides novel sulfonamide derivatives as a generic method adapted for --NH-protective groups in organic synthesis. Moreover, the invention relates to Glutathione S-transferase (GST)/Reduced Glutathione (GSH) as a means for the release of a protected amino derivative that has been conjugated to specific electrophilic moieties via a sulfonamide bond. The precursor is a synthetic intermediate carrying a free --NH-which has been derivatized by the attachment of an electrophile via a sulfonamide bond. The purpose of such a modification is to protect the free amino group during the chemical synthesis. The protected intermediate is recognized and bound by GST which catalyses the nucleophilic attack of GSH to the electrophilic part of the protected intermediate in a process that releases the desired intermediate harboring the free amino group under mild experimental conditions. A recent review article by J. D. Hayes and D. J. Pulford, Crit. Rev. Biochem. Mol. Biol. (1995) 30(6): 445-600, provides an illuminating overview of the GST supergene family and a detailed account of the individual isozymes' roles in protection against toxic agents and oxidative stress; it also offers
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insights into the various isozymes' regulation in diseased tissues, especially in cancer, and into their mechanisms of catalysis. Web site: http://appft1.uspto.gov/netahtml/PTO/search-bool.html •
Therapeutic compositions containing glutathione analogs Inventor(s): Kauvar, Lawrence M.; (San Francisco, CA), Kozlowski, Michael R.; (Poway, CA), Lum, Robert T.; (Palo Alto, CA), Lyttle, Matthew H.; (Point Reyes Station, CA), Macsata, Robert W.; (Pleasanton, CA), Schow, Steven R.; (Redwood Shores, CA), Villar, Hugo O.; (La Jolla, CA) Correspondence: Heller Ehrman White & Mcauliffe Llp; 275 Middlefield Road; Menlo Park; CA; 94025-3506; US Patent Application Number: 20030100511 Date filed: July 10, 2001 Abstract: Pharmaceutical compositions and methods of using them. Lipid formulations of a glutathione analog and methods of manufacturing them. Their use to stimulate hematopoiesis, protect hematopoietic cells from damage caused by radiation or chemotherapy, or potentiate the stimulatory action of one or a combination of cytokines on colony formation by hematopoietic progenitor cells, protect a subject from a destructive effect of a chemotherapeutic agent or irradiation, or to potentiate the effect of a chemotherapeutic agent. Excerpt(s): The invention relates to compositions, formulations and methods of certain glutathione analogs which interact with at least one glutathione S-transferase. The invention further relates to lipid formulations of a glutathione analog and to their process of manufacture. The lipid formulations overcome the insolubility problem of the drug when administered parenterally and decrease its toxic effects. Finally, the invention is directed to modulation of hematopoiesis in bone marrow or blood and to other useful responses provided by such compositions and formulations. The side effects of chemotherapeutic agents used in the treatment of malignancy and other indications are well known. Among these side effects are alterations in the levels of various blood cells, including neutrophils, platelets and lymphocytes. The results of these effects can be neutropenia, thrombocytopenia and general immune suppression. These side effects are not only unpleasant, but they also restrict the efficacy of cancer therapy and place the subject at serious risk of infection and uncontrolled bleeding. At the present time, there is little practical remediation for these effects. Typically, the approaches are supportive care, large doses of antibiotics or the administration of growth factors. The administration of growth factors, such as granulocyte colonystimulating factor (GCSF), granulocyte macrophage colony-stimulating factor (GMCSF), and more newly developed factors such as megakaryocyte growth and development factor (MGDF) and thrombopoietin (TPO) are costly. In addition, they have their own associated negative side effects. Web site: http://appft1.uspto.gov/netahtml/PTO/search-bool.html
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Treatment of acne using alkanolamine compositions Inventor(s): Perricone, Nicholas V.; (Guilford, CT) Correspondence: Mary M. Krinsky, PH. D., J.D.; Patent Attorney; 79 Trumbull Street; New Haven; CT; 06511; US Patent Application Number: 20030021855 Date filed: February 27, 2002 Abstract: Acne is treated or prevented by the topical application of compositions containing an alkanolamine such as dimethylaminoethanol, tyrosine, and a sulfur ingredient such as lipoic acid or glutathione. Adjunct ingredients such as fatty acid esters of ascorbic acid, e.g., ascorbyl palmitate and.alpha.-hydroxy acids may be included in the formulations. Compositions of the invention may be used alone, or, in many preferable embodiments, in combination with conventional acne medications such as anti-acne products containing salicylic acid, benzoyl peroxide, or a retinoid. In these embodiments, alkanolamine compositions of the invention are applied to affected skin areas first, and then a conventional acne medication is applied. This maximizes the efficacy of the treatment while minimizing skin irritation caused by conventional medications. Excerpt(s): This is a continuation-in-part of co-pending U.S. patent application Ser. No. 09/900,680, filed Jul. 6, 2001. This invention relates to improved compositions and methods for the treatment and prevention of acne, and the promotion of clear skin. This invention relates primarily to methods and compositions for the treatment of acne vulgaris. Acne is the most common pustular condition of the skin, disfiguring afflicted persons with inflammatory and noninflammatory lesions (including pustules, papules and comedones) during the active phase, and with atrophic scars afterwards. It occurs most commonly in teenagers, but is not confined to adolescents, as increasing numbers of persons aged >20 years are seeking advice on treatment for acne (Brogden, R. N., and Goa, K. L., Drugs, 1997, 53: 511-519; this reference and others cited below are hereby incorporated herein in their entireties by reference). Although acne is generally considered to be self-limiting, its social effects can be substantial, and it may have its most severe effects on the psyche (ibid.). In about 60% of teenagers, disease severity and embarrassment are sufficient for them to self-medicate with proprietary preparations and/or seek medical advice. Web site: http://appft1.uspto.gov/netahtml/PTO/search-bool.html
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Unit dosage forms for the treatment of herpes simplex Inventor(s): Pearson, Don C.; (Lakewood, WA), Richardson, Kenneth T.; (Anchorage, AK) Correspondence: Townsend And Townsend And Crew, Llp; Two Embarcadero Center; Eighth Floor; San Francisco; CA; 94111-3834; US Patent Application Number: 20020197313 Date filed: July 30, 2002 Abstract: The components of this invention are chosen because of their complementarity for the prevention or treatment of diseases caused by the herpes simplex virus. L-Lysine favorably increases the physiologic immunomodulation necessary for defense against this virus. Zinc improves and maintains a normal immune response. 2-Deoxy-2-D-
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glucose and heparin sodium alter the surface interaction between the herpes virus and the cell, preventing fusion and infectivity. N-Acetyl-L-cysteine increases glutathione levels thereby creating a thiol redox barrier to the virus at the cell membrane. Quercetin reduces intracellular replication of the herpes virus and viral infectivity. Ascorbate, in concert with copper and D-.alpha.-tocopherol, provides an antioxidant defense against the herpes virus, which tends to lose latency during period of oxidative, free radical excess. Selenium and quercetin also participate in reducing various oxidative stresses. Together the components of this invention provide the potential for improved resistance to, improved recovery from, and a decreased frequency of recurrence of herpes simplex virus infection. Excerpt(s): This application is related to U.S. Provisional Patent Application No. 60/101,308, filed Sep. 21, 1998, and claims all benefits legally available therefrom. Provisional Patent Application No. 60/101,308 is hereby incorporated by reference for all purposes capable of being served thereby. This invention is in the field of pharmacology, and relates specifically to the pharmacological treatment of conditions associated with herpes simplex virus infections. No human virus is considered normal flora; although some viruses may be more or less symptomatic, unlike bacteria none can be considered non-pathogenic. And because the viral life cycle is played out within a host cell, the membrane and molecular function of the target eukaryocyte and the biological life cycle of the invasive virion are inextricably entwined. Web site: http://appft1.uspto.gov/netahtml/PTO/search-bool.html •
Use of substituted acryloyl distamycin derivatives in the treatment of tumors associated with high levels of glutathione Inventor(s): Beria, Italo; (Milano, IT), Cozzi, Paolo; (Milano, IT), Geroni, Maria Cristina; (Milano, IT) Correspondence: Nikaido Marmelstein Murray & Oram; Metropolitan Square; Suite 330 G Street Lobby; 665 Fifteenth Street N W; Washington; DC; 20005-5701; US Patent Application Number: 20030207794 Date filed: November 7, 2002 Abstract: Compounds which are.alpha.-halogenoacryloyl distamycin derivatives of formula (I) wherein R.sub.1 is a bromine or chlorine atom; R.sub.2 is a distamycin or distamycin-like framework as set forth in the specification; or a pharmaceutically acceptable salt thereof; are cytotoxic agents particularly effective in the treatment of tumors over expressing GSH/GSTs system and which are poorly responsive or even resistant to conventional antitumor therapies. Excerpt(s): The present invention relates to the use of substituted acryloyl distamycin derivatives, in particular to the use of.alpha.-bromo- and.alpha.-chloroacryloyl distamycin derivatives, in the treatment of tumors associated with high levels of glutathione and/or glutathione-S-transfera- ses family. More specifically, the present invention concerns the treatment of a human being diagnosed with a tumor over expressing glutathione/glutathione-S-transferases family, hereinafter solely referred to as GSH/GSTs, with the above acryloyl distamycin derivatives. GSH plays a crucial protective role against cellular injury produced by a number of toxic insults. Preclinical and clinical studies have established a correlation between GSH/GSTs over expression and cancer or cancer response-rate to chemotherapy. Web site: http://appft1.uspto.gov/netahtml/PTO/search-bool.html
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Keeping Current In order to stay informed about patents and patent applications dealing with glutathione, 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 “glutathione” (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 glutathione. You can also use this procedure to view pending patent applications concerning glutathione. Simply go back to http://www.uspto.gov/patft/index.html. Select “Quick Search” under “Published Applications.” Then proceed with the steps listed above.
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CHAPTER 6. BOOKS ON GLUTATHIONE Overview This chapter provides bibliographic book references relating to glutathione. In addition to online booksellers such as www.amazon.com and www.bn.com, excellent sources for book titles on glutathione 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 “glutathione” at online booksellers’ Web sites, you may discover non-medical books that use the generic term “glutathione” (or a synonym) in their titles. The following is indicative of the results you might find when searching for “glutathione” (sorted alphabetically by title; follow the hyperlink to view more details at Amazon.com): •
Alpha-Class Glutathione Transferases As Steroid Isomerases & Scaffolds for Protein Redesign (Comprehensive Summaries of Uppsala Dissertations from the Faculty Science aNd Technology, 719) by Par L. Pettersson (2002); ISBN: 9155453279; http://www.amazon.com/exec/obidos/ASIN/9155453279/icongroupinterna
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Biothiols, Part B: Glutathione & Thioredoxin: Thiols in Signal Transduction & Gene Regulation by Lester Packer (Editor), et al; ISBN: 0121821536; http://www.amazon.com/exec/obidos/ASIN/0121821536/icongroupinterna
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Catalysis by Theta-Class Glutathione Transferases: Substrate Binding, Product Formation and Product Release (Comprehensive Summaries of Uppsala Dissertations from the Faculty of sciencE and Technology, 543) by Per Jemth (2000); ISBN: 915544735X; http://www.amazon.com/exec/obidos/ASIN/915544735X/icongroupinterna
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Exploring the Functional Plasticity of Human Glutathione Transferases: Allelic Variants, Novel Isoenzyme & Enzyme Redesign (Comprehensive Summaries of
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Uppsala Dissertations from the Faculty of sciencE and Technology, 695) by Ann-Sofie Johansson (2002); ISBN: 9155452701; http://www.amazon.com/exec/obidos/ASIN/9155452701/icongroupinterna •
Functions of glutathione in liver and kidney; ISBN: 0387091270; http://www.amazon.com/exec/obidos/ASIN/0387091270/icongroupinterna
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Functions of Glutathione: Biochemical, Physiological, Toxicological, and Clinical Aspects by Agne Larsson; ISBN: 0890049084; http://www.amazon.com/exec/obidos/ASIN/0890049084/icongroupinterna
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Glutamate, Glutamine, Glutathione, and Related Compunds : Volume 113: Glutamente, Glutamine, Glutathione and Related Compounds by Alton Meister (Editor), et al (1985); ISBN: 0121820130; http://www.amazon.com/exec/obidos/ASIN/0121820130/icongroupinterna
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Glutathione; ISBN: 999157607X; http://www.amazon.com/exec/obidos/ASIN/999157607X/icongroupinterna
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Glutathione (GSH) : Your Body's Most Powerful Healing Agent by Stephen Schettini, Dr. Jimmy Gutman (1998); ISBN: 0968707823; http://www.amazon.com/exec/obidos/ASIN/0968707823/icongroupinterna
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Glutathione Centennial: Molecular Perspectives and Clinical Implications by Naoyuki Taniguchi, et al; ISBN: 0126832757; http://www.amazon.com/exec/obidos/ASIN/0126832757/icongroupinterna
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Glutathione Conjugation: Mechanisms and Biological Significance by Helmut Sies (Editor), Brian Ketterer (Editor); ISBN: 0126427550; http://www.amazon.com/exec/obidos/ASIN/0126427550/icongroupinterna
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Glutathione in the Nervous System by Christopher A. Shaw (Editor); ISBN: 1560326433; http://www.amazon.com/exec/obidos/ASIN/1560326433/icongroupinterna
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Glutathione Metabolism and Psychological Functions (Life Chemistry Reports Series) by J. Vina, G. Tsez; ISBN: 3718603799; http://www.amazon.com/exec/obidos/ASIN/3718603799/icongroupinterna
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Glutathione S-Transferases [DOWNLOAD: MICROSOFT READER] by G. J. Mulder (Editor), et al (1996); ISBN: B0000W63VS; http://www.amazon.com/exec/obidos/ASIN/B0000W63VS/icongroupinterna
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Glutathione S-Transferases and Carcinogenesis by T.J. Mantle, et al (1987); ISBN: 0850663946; http://www.amazon.com/exec/obidos/ASIN/0850663946/icongroupinterna
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Glutathione S-Transferases and Drug Resistance by J.D. Hayes, et al (1990); ISBN: 0850667895; http://www.amazon.com/exec/obidos/ASIN/0850667895/icongroupinterna
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Glutathione S-Transferases: Structure, Function and Clinical Implications by G.J. Mulder, et al; ISBN: 0748403310; http://www.amazon.com/exec/obidos/ASIN/0748403310/icongroupinterna
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Glutathione: Chemical, Biochemical And, Medical (Pt B) by David A. Dolphin, et al; ISBN: 0471601845; http://www.amazon.com/exec/obidos/ASIN/0471601845/icongroupinterna
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Glutathione: Chemical, Biochemical, and Medical Aspects, Part A by David Dolphin, et al; ISBN: 0471097845; http://www.amazon.com/exec/obidos/ASIN/0471097845/icongroupinterna
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Glutathione: Chemical, Biochemical, and Medical Aspects/Parts A and B (Coenzymes and Cofactors, Vol 3) by David Dolphin (Editor), et al; ISBN: 0471609501; http://www.amazon.com/exec/obidos/ASIN/0471609501/icongroupinterna
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Glutathione: Metabolism and Physiological Functions by Jose M.D. Vina (Editor), et al; ISBN: 0849332745; http://www.amazon.com/exec/obidos/ASIN/0849332745/icongroupinterna
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Glutathione: The Ultimate Antioxidant by Alan H. Pressman, Sheila Buff (Contributor); ISBN: 0312964323; http://www.amazon.com/exec/obidos/ASIN/0312964323/icongroupinterna
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GSH Your Body's Most Powerful Protector GLUTATHIONE, Third Edition by Jimmy Gutman; ISBN: 0973140909; http://www.amazon.com/exec/obidos/ASIN/0973140909/icongroupinterna
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Molecular Genetic Studies of 3 Autosomal Recessive Disorders: Sjogren-Larsson Syndrome, Glutathione Synthetase Deficiency and Congenital Ichthyosis (Comprehensive Summaries of Uppsala Dissertations, 928) by Maritta Pigg (2000); ISBN: 915544718X; http://www.amazon.com/exec/obidos/ASIN/915544718X/icongroupinterna
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Redesign of Alpha Class Glutathione Transferases to Study Their Catalytic Properties (Comprehensive Summaries of Uppsala Dissertations from the Faculty of sciencE and Technology, 672) by Lisa O. Nilsson (2001); ISBN: 9155451713; http://www.amazon.com/exec/obidos/ASIN/9155451713/icongroupinterna
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Redesign of Substrate Specificity of Glutathione Transferase and Glutathione Reductase: Enzyme Engineering by Directed Mutagenesis, Phage-Display Selection and DNA Shuffling (Comprehensive Summaries of Uppsala Dissertations, 450) by Lars O. Hansson (1999); ISBN: 915544458X; http://www.amazon.com/exec/obidos/ASIN/915544458X/icongroupinterna
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Significance of Glutathione to Plant Adaptation to the Environment (Kluwer Handbook Series of Plant Ecophysiology) by Dieter Grill (Editor), et al; ISBN: 1402001789; http://www.amazon.com/exec/obidos/ASIN/1402001789/icongroupinterna
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Structure and Function of Glutathione S-Transferases by Kenneth D., Ph.D. Tew, Cecil B., Ph.D. Pickett; ISBN: 0849345820; http://www.amazon.com/exec/obidos/ASIN/0849345820/icongroupinterna
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The evolution of glutathione metabolism in phototrophic microorganisms (SuDoc NAS 1.26:182902) by Robert C. Fahey; ISBN: B000105180; http://www.amazon.com/exec/obidos/ASIN/B000105180/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 “glutathione” (or synonyms) into the search box, and select “books only.”
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From there, results can be sorted by publication date, author, or relevance. The following was recently catalogued by the National Library of Medicine:10 •
Effects of oxygen and reduced glutathione on the oxygen consumption of mouse liver: May 1975, final report Author: Baeyens, Dennis A.; Year: 1980; Washington: US Army Medical Research and Development Command, 1975
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Enzymatic synthesis and hydrolysis of glutathione thiol esters in liver: purification and properties of formaldehyde dehydrogenase, glyoxalase I and glutathione thiol esterases Author: Uotila, Lasse.; Year: 1974; Helsinki: [s.n.], 1974
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Glutathione: metabolism and function Author: Arias, Irwin M.; Year: 1978; New York: Raven Press, c1976; ISBN: 0890040621 http://www.amazon.com/exec/obidos/ASIN/0890040621/icongroupinterna
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Glutathione: storage, transport and turnover in mammals Author: Sakamoto, Y. (Yukiya); Year: 1990; Tokoyo: Japan Scientific Societies Press, c1983; ISBN: 9067640026
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Glutathione. Author: Crook, Eric Mitchell,; Year: 1957; Cambridge [Eng.] University Press, 1959
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Glutathione; proceedings of the symposium. Editors: S. Colowick [and others]. Author: Colowick, Sidney P.; Year: 1976; New York, Academic Press, 1954
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Measurement of blood glutathione peroxidase activity for assessment of selenium nutrition in livestock Author: Paynter, D. I.; Year: 1936; East Melbourne, Vic., Australia: Published for the Australian Agricultural Council (Standing Committee on Agriculture) by CSIRO Australia, 1985; ISBN: 0643041214
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Renal metabolism of glutathione Author: Ormstad, Kari.; Year: 1970; Stockholm: [s.n.], 1980; ISBN: 9172223553
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Selenium and glutathione peroxidase in rats and humans: with special reference to bioavailability, pregnancy, and liver function Author: Korpela, Heikki.; Year: 1968; Oulu: University of Oulu, 1990; ISBN: 9514229584
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Selenium, glutathione peroxidase and some metal ions in male reproductive system Author: Saaranen, Markku.; Year: 1990; Kuopio: Departments of Anatomy and Gynaecology, University of Kuopio, 1989; ISBN: 9517802706
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The significance of glutathione S-transferases in biochemical toxicology: kinetic and binding studies designed to establish a mechanism of action of glutathione Stransferase A from rat liver Author: Jakobson, Inga.; Year: 1993; Stockholm: Dept. of Biochemistry, Arrhenius Laboratory, University of Stockholm, 1979; ISBN: 9174640623
Chapters on Glutathione In order to find chapters that specifically relate to glutathione, an excellent source of abstracts is the Combined Health Information Database. You will need to limit your search to book chapters and glutathione using the “Detailed Search” option. Go to the following 10
In addition to LOCATORPlus, in collaboration with authors and publishers, the National Center for Biotechnology Information (NCBI) is currently adapting biomedical books for the Web. The books may be accessed in two ways: (1) by searching directly using any search term or phrase (in the same way as the bibliographic database PubMed), or (2) by following the links to PubMed abstracts. Each PubMed abstract has a "Books" button that displays a facsimile of the abstract in which some phrases are hypertext links. These phrases are also found in the books available at NCBI. Click on hyperlinked results in the list of books in which the phrase is found. Currently, the majority of the links are between the books and PubMed. In the future, more links will be created between the books and other types of information, such as gene and protein sequences and macromolecular structures. See http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=Books.
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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 “glutathione” (or synonyms) into the “For these words:” box. The following is a typical result when searching for book chapters on glutathione: •
Physiology of Digestion, Absorption, and Metabolism in the Human Intestine Source: in Preedy, V.R. and Watson, R.R., eds. Alcohol and the Gastrointestinal Tract. Boca Raton, FL: CRC Press. 1996. p. 79-110. Contact: Available from CRC Press. 2000 Corporate Boulevard NW., Boca Raton, FL 33431. (800) 272-7737 or (561) 994-0555. Fax (800) 374-3401. E-mail:
[email protected]. Website: http://www.crcpress.com. PRICE: $179.00. ISBN: 0849324807. Summary: This chapter, from a medical text on alcohol and the gastrointestinal tract, addresses the most significant features of digestion, absorption, and intestinal metabolism and how they are affected by alcohol consumption. The section on digestion and absorption in the small intestine covers protein, carbohydrate, fat absorption, water, and electrolytes. Other topics include the nutrition of the intestinal mucosa; and principal substrates for small intestinal metabolism, including glutamine, glutathione, nucleotides, arginine, urea and luminal protein. 4 figures. 5 tables. 253 references.
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CHAPTER 7. PERIODICALS AND NEWS ON GLUTATHIONE Overview In this chapter, we suggest a number of news sources and present various periodicals that cover glutathione.
News Services and Press Releases One of the simplest ways of tracking press releases on glutathione 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 “glutathione” (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 glutathione. 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 “glutathione” (or synonyms). The following was recently listed in this archive for glutathione: •
Myeloperoxidase and glutathione peroxidase 1 may predict cardiac events Source: Reuters Medical News Date: October 22, 2003
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Glutathione improves walking, hemodynamics in peripheral artery disease Source: Reuters Industry Breifing Date: August 23, 2002
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Elevated blast glutathione levels predict relapse in childhood ALL Source: Reuters Medical News Date: January 18, 2001
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Sputum glutathione levels not elevated in asthmatics Source: Reuters Medical News Date: January 10, 2001
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N-acetylcysteine treats glutathione deficiency in HIV-infected patients Source: Reuters Medical News Date: November 23, 2000
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N-acetylcysteine supplementation increases glutathione synthesis in HIV infection Source: Reuters Medical News Date: January 21, 1999
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Glutathione infusion enhances coronary blood flow during oxidative stress Source: Reuters Medical News Date: June 19, 1998
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Glutathione S-transferase Polymorphisms Increase Breast Cancer Risk Source: Reuters Medical News Date: April 01, 1998
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Plasma Glutathione Concentration Deficient In HIV-Infected Children Source: Reuters Medical News Date: March 23, 1998
•
Glutathione-Enhancing Drug Reduces Noise-Induced Hearing Loss Source: Reuters Medical News Date: September 15, 1997
•
Glutathione Spray Prompts Airway Problems in Asthmatics Source: Reuters Medical News Date: August 28, 1997
•
Glutathione Deficiency Predicts Poor Survival In HIV-Positive Subjects Source: Reuters Medical News Date: March 04, 1997
•
Glutathione Helps AIDS Survival Source: Reuters Health eLine Date: March 03, 1997
•
Glutathione Replacement Therapy Suggested For HIV-Positive Patients With HCV Source: Reuters Medical News Date: December 17, 1996
•
Glutathione: A Possible Blocker Of HIV-1 Reverse Transcriptase Source: Reuters Medical News Date: December 04, 1996
•
Glutathione May Have Role In AIDS Treatment Source: Reuters Medical News Date: November 19, 1996
•
Study Set For Glutathione Peroxidase-Like Molecule Source: Reuters Medical News Date: June 20, 1996
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The NIH Within MEDLINEplus, the NIH has made an agreement with the New York Times Syndicate, the AP News Service, and Reuters to deliver news that can be browsed by the public. Search news releases at http://www.nlm.nih.gov/medlineplus/alphanews_a.html. MEDLINEplus allows you to browse across an alphabetical index. Or you can search by date at the following Web page: http://www.nlm.nih.gov/medlineplus/newsbydate.html. Often, news items are indexed by MEDLINEplus within its search engine. Business Wire Business Wire is similar to PR Newswire. To access this archive, simply go to http://www.businesswire.com/. You can scan the news by industry category or company name. Market Wire Market Wire is more focused on technology than the other wires. To browse the latest press releases by topic, such as alternative medicine, biotechnology, fitness, healthcare, legal, nutrition, and pharmaceuticals, access Market Wire’s Medical/Health channel at http://www.marketwire.com/mw/release_index?channel=MedicalHealth. Or simply go to Market Wire’s home page at http://www.marketwire.com/mw/home, type “glutathione” (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 “glutathione” (or synonyms). If you know the name of a company that is relevant to glutathione, 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 “glutathione” (or synonyms).
Academic Periodicals covering Glutathione Numerous periodicals are currently indexed within the National Library of Medicine’s PubMed database that are known to publish articles relating to glutathione. In addition to
220 Glutathione
these sources, you can search for articles covering glutathione that have been published by any of the periodicals listed in previous chapters. To find the latest studies published, go to http://www.ncbi.nlm.nih.gov/pubmed, type the name of the periodical into the search box, and click “Go.” If you want complete details about the historical contents of a journal, you can also visit the following Web site: http://www.ncbi.nlm.nih.gov/entrez/jrbrowser.cgi. Here, type in the name of the journal or its abbreviation, and you will receive an index of published articles. At http://locatorplus.gov/, you can retrieve more indexing information on medical periodicals (e.g. the name of the publisher). Select the button “Search LOCATORplus.” Then type in the name of the journal and select the advanced search option “Journal Title Search.”
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APPENDICES
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APPENDIX A. PHYSICIAN RESOURCES Overview In this chapter, we focus on databases and Internet-based guidelines and information resources created or written for a professional audience.
NIH Guidelines Commonly referred to as “clinical” or “professional” guidelines, the National Institutes of Health publish physician guidelines for the most common diseases. Publications are available at the following by relevant Institute11: •
Office of the Director (OD); guidelines consolidated across agencies available at http://www.nih.gov/health/consumer/conkey.htm
•
National Institute of General Medical Sciences (NIGMS); fact sheets available at http://www.nigms.nih.gov/news/facts/
•
National Library of Medicine (NLM); extensive encyclopedia (A.D.A.M., Inc.) with guidelines: http://www.nlm.nih.gov/medlineplus/healthtopics.html
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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
•
National Institute on Aging (NIA); guidelines available at http://www.nia.nih.gov/health/
11
These publications are typically written by one or more of the various NIH Institutes.
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•
National Institute on Alcohol Abuse and Alcoholism (NIAAA); guidelines available at http://www.niaaa.nih.gov/publications/publications.htm
•
National Institute of Allergy and Infectious Diseases (NIAID); guidelines available at http://www.niaid.nih.gov/publications/
•
National Institute of Arthritis and Musculoskeletal and Skin Diseases (NIAMS); fact sheets and guidelines available at http://www.niams.nih.gov/hi/index.htm
•
National Institute of Child Health and Human Development (NICHD); guidelines available at http://www.nichd.nih.gov/publications/pubskey.cfm
•
National Institute on Deafness and Other Communication Disorders (NIDCD); fact sheets and guidelines at http://www.nidcd.nih.gov/health/
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National Institute of Dental and Craniofacial Research (NIDCR); guidelines available at http://www.nidr.nih.gov/health/
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National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK); guidelines available at http://www.niddk.nih.gov/health/health.htm
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National Institute on Drug Abuse (NIDA); guidelines available at http://www.nida.nih.gov/DrugAbuse.html
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National Institute of Environmental Health Sciences (NIEHS); environmental health information available at http://www.niehs.nih.gov/external/facts.htm
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National Institute of Mental Health (NIMH); guidelines available at http://www.nimh.nih.gov/practitioners/index.cfm
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National Institute of Neurological Disorders and Stroke (NINDS); neurological disorder information pages available at http://www.ninds.nih.gov/health_and_medical/disorder_index.htm
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National Institute of Nursing Research (NINR); publications on selected illnesses at http://www.nih.gov/ninr/news-info/publications.html
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National Institute of Biomedical Imaging and Bioengineering; general information at http://grants.nih.gov/grants/becon/becon_info.htm
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Center for Information Technology (CIT); referrals to other agencies based on keyword searches available at http://kb.nih.gov/www_query_main.asp
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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
•
Office of Rare Diseases; various fact sheets available at http://rarediseases.info.nih.gov/html/resources/rep_pubs.html
•
Centers for Disease Control and Prevention; various fact sheets on infectious diseases available at http://www.cdc.gov/publications.htm
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NIH Databases In addition to the various Institutes of Health that publish professional guidelines, the NIH has designed a number of databases for professionals.12 Physician-oriented resources provide a wide variety of information related to the biomedical and health sciences, both past and present. The format of these resources varies. Searchable databases, bibliographic citations, full-text articles (when available), archival collections, and images are all available. The following are referenced by the National Library of Medicine:13 •
Bioethics: Access to published literature on the ethical, legal, and public policy issues surrounding healthcare and biomedical research. This information is provided in conjunction with the Kennedy Institute of Ethics located at Georgetown University, Washington, D.C.: http://www.nlm.nih.gov/databases/databases_bioethics.html
•
HIV/AIDS Resources: Describes various links and databases dedicated to HIV/AIDS research: http://www.nlm.nih.gov/pubs/factsheets/aidsinfs.html
•
NLM Online Exhibitions: Describes “Exhibitions in the History of Medicine”: http://www.nlm.nih.gov/exhibition/exhibition.html. Additional resources for historical scholarship in medicine: http://www.nlm.nih.gov/hmd/hmd.html
•
Biotechnology Information: Access to public databases. The National Center for Biotechnology Information conducts research in computational biology, develops software tools for analyzing genome data, and disseminates biomedical information for the better understanding of molecular processes affecting human health and disease: http://www.ncbi.nlm.nih.gov/
•
Population Information: The National Library of Medicine provides access to worldwide coverage of population, family planning, and related health issues, including family planning technology and programs, fertility, and population law and policy: http://www.nlm.nih.gov/databases/databases_population.html
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Cancer Information: Access to cancer-oriented databases: http://www.nlm.nih.gov/databases/databases_cancer.html
•
Profiles in Science: Offering the archival collections of prominent twentieth-century biomedical scientists to the public through modern digital technology: http://www.profiles.nlm.nih.gov/
•
Chemical Information: Provides links to various chemical databases and references: http://sis.nlm.nih.gov/Chem/ChemMain.html
•
Clinical Alerts: Reports the release of findings from the NIH-funded clinical trials where such release could significantly affect morbidity and mortality: http://www.nlm.nih.gov/databases/alerts/clinical_alerts.html
•
Space Life Sciences: Provides links and information to space-based research (including NASA): http://www.nlm.nih.gov/databases/databases_space.html
•
MEDLINE: Bibliographic database covering the fields of medicine, nursing, dentistry, veterinary medicine, the healthcare system, and the pre-clinical sciences: http://www.nlm.nih.gov/databases/databases_medline.html
12
Remember, for the general public, the National Library of Medicine recommends the databases referenced in MEDLINEplus (http://medlineplus.gov/ or http://www.nlm.nih.gov/medlineplus/databases.html). 13 See http://www.nlm.nih.gov/databases/databases.html.
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•
Toxicology and Environmental Health Information (TOXNET): Databases covering toxicology and environmental health: http://sis.nlm.nih.gov/Tox/ToxMain.html
•
Visible Human Interface: Anatomically detailed, three-dimensional representations of normal male and female human bodies: http://www.nlm.nih.gov/research/visible/visible_human.html The Combined Health Information Database
A comprehensive source of information on clinical guidelines written for professionals is the Combined Health Information Database. You will need to limit your search to one of the following: Brochure/Pamphlet, Fact Sheet, or Information Package, and “glutathione” using the “Detailed Search” option. Go directly to the following hyperlink: http://chid.nih.gov/detail/detail.html. To find associations, use the drop boxes at the bottom of the search page where “You may refine your search by.” For the publication date, select “All Years.” Select your preferred language and the format option “Fact Sheet.” Type “glutathione” (or synonyms) into the “For these words:” box. The following is a sample result: •
NAC (N - Acetyl Cysteine) and Glutathione Contact: AIDS Project Los Angeles, 3550 Wilshire Blvd Ste 300, Los Angeles, CA, 900102404, (213) 201-1600, http://www.apla.org. Summary: This report compiles information on N-Acetyl cysteine (NAC), a wellestablished drug which may be useful in combination therapy for AIDS. Factsheets explain what NAC is, why it is important, how to get it, and what the contraindications of its use are. In vitro studies show that NAC replenishes glutathione (GSH) because GSH deficiency contributes to AIDS morbidity. Oxidative stress in relation to HIV is discussed. As an antioxidant, NAC reverses tumor necrosis factor alpha toxicity in cells and in animals. Currently approved antiretroviral drugs do not inhibit HIV production once they integrate into the cell's genome; this appears to be the mechanism of action for NAC. Clinical trials are planned to study NAC and GSH for use in AIDS therapy.
The NLM Gateway14 The NLM (National Library of Medicine) Gateway is a Web-based system that lets users search simultaneously in multiple retrieval systems at the U.S. National Library of Medicine (NLM). It allows users of NLM services to initiate searches from one Web interface, providing one-stop searching for many of NLM’s information resources or databases.15 To use the NLM Gateway, simply go to the search site at http://gateway.nlm.nih.gov/gw/Cmd. Type “glutathione” (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.
14 15
Adapted from NLM: http://gateway.nlm.nih.gov/gw/Cmd?Overview.x.
The NLM Gateway is currently being developed by the Lister Hill National Center for Biomedical Communications (LHNCBC) at the National Library of Medicine (NLM) of the National Institutes of Health (NIH).
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Results Summary Category Journal Articles Books / Periodicals / Audio Visual Consumer Health Meeting Abstracts Other Collections Total
Items Found 58349 114 415 104 0 58982
HSTAT16 HSTAT is a free, Web-based resource that provides access to full-text documents used in healthcare decision-making.17 These documents include clinical practice guidelines, quickreference guides for clinicians, consumer health brochures, evidence reports and technology assessments from the Agency for Healthcare Research and Quality (AHRQ), as well as AHRQ’s Put Prevention Into Practice.18 Simply search by “glutathione” (or synonyms) at the following Web site: http://text.nlm.nih.gov.
Coffee Break: Tutorials for Biologists19 Coffee Break is a general healthcare site that takes a scientific view of the news and covers recent breakthroughs in biology that may one day assist physicians in developing treatments. Here you will find a collection of short reports on recent biological discoveries. Each report incorporates interactive tutorials that demonstrate how bioinformatics tools are used as a part of the research process. Currently, all Coffee Breaks are written by NCBI staff.20 Each report is about 400 words and is usually based on a discovery reported in one or more articles from recently published, peer-reviewed literature.21 This site has new articles every few weeks, so it can be considered an online magazine of sorts. It is intended for general background information. You can access the Coffee Break Web site at the following hyperlink: http://www.ncbi.nlm.nih.gov/Coffeebreak/.
16
Adapted from HSTAT: http://www.nlm.nih.gov/pubs/factsheets/hstat.html.
17
The HSTAT URL is http://hstat.nlm.nih.gov/.
18
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. 19 Adapted from http://www.ncbi.nlm.nih.gov/Coffeebreak/Archive/FAQ.html. 20
The figure that accompanies each article is frequently supplied by an expert external to NCBI, in which case the source of the figure is cited. The result is an interactive tutorial that tells a biological story. 21 After a brief introduction that sets the work described into a broader context, the report focuses on how a molecular understanding can provide explanations of observed biology and lead to therapies for diseases. Each vignette is accompanied by a figure and hypertext links that lead to a series of pages that interactively show how NCBI tools and resources are used in the research process.
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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 Glutathione In the following section, we will discuss databases and references which relate to the Genome Project and glutathione. 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).22 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. To search the database, go to http://www.ncbi.nlm.nih.gov/Omim/searchomim.html. Type “glutathione” (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 glutathione: •
Glutathione Peroxidase Web site: http://www.ncbi.nlm.nih.gov/htbin-post/Omim/dispmim?138320
•
Glutathione Peroxidase 2 Web site: http://www.ncbi.nlm.nih.gov/htbin-post/Omim/dispmim?138319
•
Glutathione Peroxidase 3 Web site: http://www.ncbi.nlm.nih.gov/htbin-post/Omim/dispmim?138321
•
Glutathione Peroxidase 4 Web site: http://www.ncbi.nlm.nih.gov/htbin-post/Omim/dispmim?138322
•
Glutathione Peroxidase 5 Web site: http://www.ncbi.nlm.nih.gov/htbin-post/Omim/dispmim?603435
22 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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Glutathione Peroxidase 6 Web site: http://www.ncbi.nlm.nih.gov/htbin-post/Omim/dispmim?607913
•
Glutathione Reductase Web site: http://www.ncbi.nlm.nih.gov/htbin-post/Omim/dispmim?138300
•
Glutathione S-transferase 6 Web site: http://www.ncbi.nlm.nih.gov/htbin-post/Omim/dispmim?138391
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Glutathione S-transferase, Alpha-1 Web site: http://www.ncbi.nlm.nih.gov/htbin-post/Omim/dispmim?138359
•
Glutathione S-transferase, Alpha-2 Web site: http://www.ncbi.nlm.nih.gov/htbin-post/Omim/dispmim?138360
•
Glutathione S-transferase, Alpha-3 Web site: http://www.ncbi.nlm.nih.gov/htbin-post/Omim/dispmim?605449
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Glutathione S-transferase, Alpha-4 Web site: http://www.ncbi.nlm.nih.gov/htbin-post/Omim/dispmim?605450
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Glutathione S-transferase, Alpha-5 Web site: http://www.ncbi.nlm.nih.gov/htbin-post/Omim/dispmim?607605
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Glutathione S-transferase, Kappa-1 Web site: http://www.ncbi.nlm.nih.gov/htbin-post/Omim/dispmim?602321
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Glutathione S-transferase, Microsomal, 1 Web site: http://www.ncbi.nlm.nih.gov/htbin-post/Omim/dispmim?138330
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Glutathione S-transferase, Microsomal, 2 Web site: http://www.ncbi.nlm.nih.gov/htbin-post/Omim/dispmim?601733
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Glutathione S-transferase, Microsomal, 3 Web site: http://www.ncbi.nlm.nih.gov/htbin-post/Omim/dispmim?604564
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Glutathione S-transferase, Mu-1 Web site: http://www.ncbi.nlm.nih.gov/htbin-post/Omim/dispmim?138350
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Glutathione S-transferase, Mu-1-like Web site: http://www.ncbi.nlm.nih.gov/htbin-post/Omim/dispmim?138270
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Glutathione S-transferase, Mu-2 Web site: http://www.ncbi.nlm.nih.gov/htbin-post/Omim/dispmim?138380
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Glutathione S-transferase, Mu-3 Web site: http://www.ncbi.nlm.nih.gov/htbin-post/Omim/dispmim?138390
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Glutathione S-transferase, Mu-4 Web site: http://www.ncbi.nlm.nih.gov/htbin-post/Omim/dispmim?138333
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Glutathione S-transferase, Mu-5 Web site: http://www.ncbi.nlm.nih.gov/htbin-post/Omim/dispmim?138385
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Glutathione S-transferase, Omega-1 Web site: http://www.ncbi.nlm.nih.gov/htbin-post/Omim/dispmim?605482
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Glutathione S-transferase, Pi Web site: http://www.ncbi.nlm.nih.gov/htbin-post/Omim/dispmim?134660
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Glutathione S-transferase, Theta-1 Web site: http://www.ncbi.nlm.nih.gov/htbin-post/Omim/dispmim?600436
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Glutathione S-transferase, Theta-2 Web site: http://www.ncbi.nlm.nih.gov/htbin-post/Omim/dispmim?600437
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Glutathione S-transferase, Zeta-1 Web site: http://www.ncbi.nlm.nih.gov/htbin-post/Omim/dispmim?603758
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Glutathione Synthetase Web site: http://www.ncbi.nlm.nih.gov/htbin-post/Omim/dispmim?601002
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Glutathione Synthetase Deficiency of Erythrocytes, Hemolytic Anemia due to Web site: http://www.ncbi.nlm.nih.gov/htbin-post/Omim/dispmim?231900
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Glutathione Transferase Activity toward Trans-stilbene Oxide Web site: http://www.ncbi.nlm.nih.gov/htbin-post/Omim/dispmim?138340
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Hydroxyacyl Glutathione Hydrolase Web site: http://www.ncbi.nlm.nih.gov/htbin-post/Omim/dispmim?138760 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
•
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
•
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
•
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
•
Nervous System: Mind and body. Examples: Alzheimer disease, amyotrophic lateral sclerosis, Angelman syndrome, Charcot-Marie-Tooth disease, epilepsy, essential tremor, fragile X syndrome,
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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 •
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
•
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
•
Books: Online books, Web site: http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=books
•
Genome: Complete genome assemblies, Web site: http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=Genome
•
NCBI’s Protein Sequence Information Survey Results: Web site: http://www.ncbi.nlm.nih.gov/About/proteinsurvey/
•
Nucleotide Sequence Database (Genbank): Web site: http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=Nucleotide
•
OMIM: Online Mendelian Inheritance in Man, Web site: http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=OMIM
•
PopSet: Population study data sets, Web site: http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=Popset
•
ProbeSet: Gene Expression Omnibus (GEO), Web site: http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=geo
•
Protein Sequence Database: Web site: http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=Protein
•
PubMed: Biomedical literature (PubMed), Web site: http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed
•
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 select the database that you would like to search. The databases available are listed in the drop box next to “Search.” Enter “glutathione” (or synonyms) into the search box and click “Go.” Jablonski’s Multiple Congenital Anomaly/Mental Retardation (MCA/MR) Syndromes Database23 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 Database24 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 “glutathione” (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).
23
Adapted from the National Library of Medicine: http://www.nlm.nih.gov/mesh/jablonski/about_syndrome.html. 24 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 glutathione 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 glutathione. 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 glutathione. 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 “glutathione”:
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•
Other guides Antioxidants http://www.nlm.nih.gov/medlineplus/antioxidants.html Dietary Fiber http://www.nlm.nih.gov/medlineplus/dietaryfiber.html Vitamin and Mineral Supplements http://www.nlm.nih.gov/medlineplus/vitaminandmineralsupplements.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 glutathione. The drawbacks of this approach are that the information is not organized by theme and that the references are often a mix of information for professionals and patients. Nevertheless, a large number of the listed Web sites provide useful background information. We can only recommend this route, therefore, for relatively rare or specific disorders, or when using highly targeted searches. To use the NIH search utility, visit the following Web page: http://search.nih.gov/index.html. Additional Web Sources A number of Web sites are available to the public that often link to government sites. These can also point you in the direction of essential information. The following is a representative sample: •
AOL: http://search.aol.com/cat.adp?id=168&layer=&from=subcats
•
Family Village: http://www.familyvillage.wisc.edu/specific.htm
•
Google: http://directory.google.com/Top/Health/Conditions_and_Diseases/
•
Med Help International: http://www.medhelp.org/HealthTopics/A.html
•
Open Directory Project: http://dmoz.org/Health/Conditions_and_Diseases/
•
Yahoo.com: http://dir.yahoo.com/Health/Diseases_and_Conditions/
•
WebMDHealth: http://my.webmd.com/health_topics
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Finding Associations There are several Internet directories that provide lists of medical associations with information on or resources relating to glutathione. By consulting all of associations listed in this chapter, you will have nearly exhausted all sources for patient associations concerned with glutathione. 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 glutathione. 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 “glutathione” (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 “glutathione”. 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 “glutathione” (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 “glutathione” (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.25
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
25
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)26: •
Alabama: Health InfoNet of Jefferson County (Jefferson County Library Cooperative, Lister Hill Library of the Health Sciences), http://www.uab.edu/infonet/
•
Alabama: Richard M. Scrushy Library (American Sports Medicine Institute)
•
Arizona: Samaritan Regional Medical Center: The Learning Center (Samaritan Health System, Phoenix, Arizona), http://www.samaritan.edu/library/bannerlibs.htm
•
California: Kris Kelly Health Information Center (St. Joseph Health System, Humboldt), http://www.humboldt1.com/~kkhic/index.html
•
California: Community Health Library of Los Gatos, http://www.healthlib.org/orgresources.html
•
California: Consumer Health Program and Services (CHIPS) (County of Los Angeles Public Library, Los Angeles County Harbor-UCLA Medical Center Library) - Carson, CA, http://www.colapublib.org/services/chips.html
•
California: Gateway Health Library (Sutter Gould Medical Foundation)
•
California: Health Library (Stanford University Medical Center), http://wwwmed.stanford.edu/healthlibrary/
•
California: Patient Education Resource Center - Health Information and Resources (University of California, San Francisco), http://sfghdean.ucsf.edu/barnett/PERC/default.asp
•
California: Redwood Health Library (Petaluma Health Care District), http://www.phcd.org/rdwdlib.html
•
California: Los Gatos PlaneTree Health Library, http://planetreesanjose.org/
•
California: Sutter Resource Library (Sutter Hospitals Foundation, Sacramento), http://suttermedicalcenter.org/library/
•
California: Health Sciences Libraries (University of California, Davis), http://www.lib.ucdavis.edu/healthsci/
•
California: ValleyCare Health Library & Ryan Comer Cancer Resource Center (ValleyCare Health System, Pleasanton), http://gaelnet.stmarysca.edu/other.libs/gbal/east/vchl.html
•
California: Washington Community Health Resource Library (Fremont), http://www.healthlibrary.org/
•
Colorado: William V. Gervasini Memorial Library (Exempla Healthcare), http://www.saintjosephdenver.org/yourhealth/libraries/
•
Connecticut: Hartford Hospital Health Science Libraries (Hartford Hospital), http://www.harthosp.org/library/
•
Connecticut: Healthnet: Connecticut Consumer Health Information Center (University of Connecticut Health Center, Lyman Maynard Stowe Library), http://library.uchc.edu/departm/hnet/
26
Abstracted from http://www.nlm.nih.gov/medlineplus/libraries.html.
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•
Connecticut: Waterbury Hospital Health Center Library (Waterbury Hospital, Waterbury), http://www.waterburyhospital.com/library/consumer.shtml
•
Delaware: Consumer Health Library (Christiana Care Health System, Eugene du Pont Preventive Medicine & Rehabilitation Institute, Wilmington), http://www.christianacare.org/health_guide/health_guide_pmri_health_info.cfm
•
Delaware: Lewis B. Flinn Library (Delaware Academy of Medicine, Wilmington), http://www.delamed.org/chls.html
•
Georgia: Family Resource Library (Medical College of Georgia, Augusta), http://cmc.mcg.edu/kids_families/fam_resources/fam_res_lib/frl.htm
•
Georgia: Health Resource Center (Medical Center of Central Georgia, Macon), http://www.mccg.org/hrc/hrchome.asp
•
Hawaii: Hawaii Medical Library: Consumer Health Information Service (Hawaii Medical Library, Honolulu), http://hml.org/CHIS/
•
Idaho: DeArmond Consumer Health Library (Kootenai Medical Center, Coeur d’Alene), http://www.nicon.org/DeArmond/index.htm
•
Illinois: Health Learning Center of Northwestern Memorial Hospital (Chicago), http://www.nmh.org/health_info/hlc.html
•
Illinois: Medical Library (OSF Saint Francis Medical Center, Peoria), http://www.osfsaintfrancis.org/general/library/
•
Kentucky: Medical Library - Services for Patients, Families, Students & the Public (Central Baptist Hospital, Lexington), http://www.centralbap.com/education/community/library.cfm
•
Kentucky: University of Kentucky - Health Information Library (Chandler Medical Center, Lexington), http://www.mc.uky.edu/PatientEd/
•
Louisiana: Alton Ochsner Medical Foundation Library (Alton Ochsner Medical Foundation, New Orleans), http://www.ochsner.org/library/
•
Louisiana: Louisiana State University Health Sciences Center Medical LibraryShreveport, http://lib-sh.lsuhsc.edu/
•
Maine: Franklin Memorial Hospital Medical Library (Franklin Memorial Hospital, Farmington), http://www.fchn.org/fmh/lib.htm
•
Maine: Gerrish-True Health Sciences Library (Central Maine Medical Center, Lewiston), http://www.cmmc.org/library/library.html
•
Maine: Hadley Parrot Health Science Library (Eastern Maine Healthcare, Bangor), http://www.emh.org/hll/hpl/guide.htm
•
Maine: Maine Medical Center Library (Maine Medical Center, Portland), http://www.mmc.org/library/
•
Maine: Parkview Hospital (Brunswick), http://www.parkviewhospital.org/
•
Maine: Southern Maine Medical Center Health Sciences Library (Southern Maine Medical Center, Biddeford), http://www.smmc.org/services/service.php3?choice=10
•
Maine: Stephens Memorial Hospital’s Health Information Library (Western Maine Health, Norway), http://www.wmhcc.org/Library/
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•
Manitoba, Canada: Consumer & Patient Health Information Service (University of Manitoba Libraries), http://www.umanitoba.ca/libraries/units/health/reference/chis.html
•
Manitoba, Canada: J.W. Crane Memorial Library (Deer Lodge Centre, Winnipeg), http://www.deerlodge.mb.ca/crane_library/about.asp
•
Maryland: Health Information Center at the Wheaton Regional Library (Montgomery County, Dept. of Public Libraries, Wheaton Regional Library), http://www.mont.lib.md.us/healthinfo/hic.asp
•
Massachusetts: Baystate Medical Center Library (Baystate Health System), http://www.baystatehealth.com/1024/
•
Massachusetts: Boston University Medical Center Alumni Medical Library (Boston University Medical Center), http://med-libwww.bu.edu/library/lib.html
•
Massachusetts: Lowell General Hospital Health Sciences Library (Lowell General Hospital, Lowell), http://www.lowellgeneral.org/library/HomePageLinks/WWW.htm
•
Massachusetts: Paul E. Woodard Health Sciences Library (New England Baptist Hospital, Boston), http://www.nebh.org/health_lib.asp
•
Massachusetts: St. Luke’s Hospital Health Sciences Library (St. Luke’s Hospital, Southcoast Health System, New Bedford), http://www.southcoast.org/library/
•
Massachusetts: Treadwell Library Consumer Health Reference Center (Massachusetts General Hospital), http://www.mgh.harvard.edu/library/chrcindex.html
•
Massachusetts: UMass HealthNet (University of Massachusetts Medical School, Worchester), http://healthnet.umassmed.edu/
•
Michigan: Botsford General Hospital Library - Consumer Health (Botsford General Hospital, Library & Internet Services), http://www.botsfordlibrary.org/consumer.htm
•
Michigan: Helen DeRoy Medical Library (Providence Hospital and Medical Centers), http://www.providence-hospital.org/library/
•
Michigan: Marquette General Hospital - Consumer Health Library (Marquette General Hospital, Health Information Center), http://www.mgh.org/center.html
•
Michigan: Patient Education Resouce Center - University of Michigan Cancer Center (University of Michigan Comprehensive Cancer Center, Ann Arbor), http://www.cancer.med.umich.edu/learn/leares.htm
•
Michigan: Sladen Library & Center for Health Information Resources - Consumer Health Information (Detroit), http://www.henryford.com/body.cfm?id=39330
•
Montana: Center for Health Information (St. Patrick Hospital and Health Sciences Center, Missoula)
•
National: Consumer Health Library Directory (Medical Library Association, Consumer and Patient Health Information Section), http://caphis.mlanet.org/directory/index.html
•
National: National Network of Libraries of Medicine (National Library of Medicine) provides library services for health professionals in the United States who do not have access to a medical library, http://nnlm.gov/
•
National: NN/LM List of Libraries Serving the Public (National Network of Libraries of Medicine), http://nnlm.gov/members/
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•
Nevada: Health Science Library, West Charleston Library (Las Vegas-Clark County Library District, Las Vegas), http://www.lvccld.org/special_collections/medical/index.htm
•
New Hampshire: Dartmouth Biomedical Libraries (Dartmouth College Library, Hanover), http://www.dartmouth.edu/~biomed/resources.htmld/conshealth.htmld/
•
New Jersey: Consumer Health Library (Rahway Hospital, Rahway), http://www.rahwayhospital.com/library.htm
•
New Jersey: Dr. Walter Phillips Health Sciences Library (Englewood Hospital and Medical Center, Englewood), http://www.englewoodhospital.com/links/index.htm
•
New Jersey: Meland Foundation (Englewood Hospital and Medical Center, Englewood), http://www.geocities.com/ResearchTriangle/9360/
•
New York: Choices in Health Information (New York Public Library) - NLM Consumer Pilot Project participant, http://www.nypl.org/branch/health/links.html
•
New York: Health Information Center (Upstate Medical University, State University of New York, Syracuse), http://www.upstate.edu/library/hic/
•
New York: Health Sciences Library (Long Island Jewish Medical Center, New Hyde Park), http://www.lij.edu/library/library.html
•
New York: ViaHealth Medical Library (Rochester General Hospital), http://www.nyam.org/library/
•
Ohio: Consumer Health Library (Akron General Medical Center, Medical & Consumer Health Library), http://www.akrongeneral.org/hwlibrary.htm
•
Oklahoma: The Health Information Center at Saint Francis Hospital (Saint Francis Health System, Tulsa), http://www.sfh-tulsa.com/services/healthinfo.asp
•
Oregon: Planetree Health Resource Center (Mid-Columbia Medical Center, The Dalles), http://www.mcmc.net/phrc/
•
Pennsylvania: Community Health Information Library (Milton S. Hershey Medical Center, Hershey), http://www.hmc.psu.edu/commhealth/
•
Pennsylvania: Community Health Resource Library (Geisinger Medical Center, Danville), http://www.geisinger.edu/education/commlib.shtml
•
Pennsylvania: HealthInfo Library (Moses Taylor Hospital, Scranton), http://www.mth.org/healthwellness.html
•
Pennsylvania: Hopwood Library (University of Pittsburgh, Health Sciences Library System, Pittsburgh), http://www.hsls.pitt.edu/guides/chi/hopwood/index_html
•
Pennsylvania: Koop Community Health Information Center (College of Physicians of Philadelphia), http://www.collphyphil.org/kooppg1.shtml
•
Pennsylvania: Learning Resources Center - Medical Library (Susquehanna Health System, Williamsport), http://www.shscares.org/services/lrc/index.asp
•
Pennsylvania: Medical Library (UPMC Health System, Pittsburgh), http://www.upmc.edu/passavant/library.htm
•
Quebec, Canada: Medical Library (Montreal General Hospital), http://www.mghlib.mcgill.ca/
242 Glutathione
•
South Dakota: Rapid City Regional Hospital Medical Library (Rapid City Regional Hospital), http://www.rcrh.org/Services/Library/Default.asp
•
Texas: Houston HealthWays (Houston Academy of Medicine-Texas Medical Center Library), http://hhw.library.tmc.edu/
•
Washington: Community Health Library (Kittitas Valley Community Hospital), http://www.kvch.com/
•
Washington: Southwest Washington Medical Center Library (Southwest Washington Medical Center, Vancouver), http://www.swmedicalcenter.com/body.cfm?id=72
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ONLINE GLOSSARIES The Internet provides access to a number of free-to-use medical dictionaries. The National Library of Medicine has compiled the following list of online dictionaries: •
ADAM Medical Encyclopedia (A.D.A.M., Inc.), comprehensive medical reference: http://www.nlm.nih.gov/medlineplus/encyclopedia.html
•
MedicineNet.com Medical Dictionary (MedicineNet, Inc.): http://www.medterms.com/Script/Main/hp.asp
•
Merriam-Webster Medical Dictionary (Inteli-Health, Inc.): http://www.intelihealth.com/IH/
•
Multilingual Glossary of Technical and Popular Medical Terms in Eight European Languages (European Commission) - Danish, Dutch, English, French, German, Italian, Portuguese, and Spanish: http://allserv.rug.ac.be/~rvdstich/eugloss/welcome.html
•
On-line Medical Dictionary (CancerWEB): http://cancerweb.ncl.ac.uk/omd/
•
Rare Diseases Terms (Office of Rare Diseases): http://ord.aspensys.com/asp/diseases/diseases.asp
•
Technology Glossary (National Library of Medicine) - Health Care Technology: http://www.nlm.nih.gov/nichsr/ta101/ta10108.htm
Beyond these, MEDLINEplus contains a very patient-friendly encyclopedia covering every aspect of medicine (licensed from A.D.A.M., Inc.). The ADAM Medical Encyclopedia can be accessed at http://www.nlm.nih.gov/medlineplus/encyclopedia.html. ADAM is also available on commercial Web sites such as drkoop.com (http://www.drkoop.com/) and Web MD (http://my.webmd.com/adam/asset/adam_disease_articles/a_to_z/a).
Online Dictionary Directories The following are additional online directories compiled by the National Library of Medicine, including a number of specialized medical dictionaries: •
Medical Dictionaries: Medical & Biological (World Health Organization): http://www.who.int/hlt/virtuallibrary/English/diction.htm#Medical
•
MEL-Michigan Electronic Library List of Online Health and Medical Dictionaries (Michigan Electronic Library): http://mel.lib.mi.us/health/health-dictionaries.html
•
Patient Education: Glossaries (DMOZ Open Directory Project): http://dmoz.org/Health/Education/Patient_Education/Glossaries/
•
Web of Online Dictionaries (Bucknell University): http://www.yourdictionary.com/diction5.html#medicine
245
GLUTATHIONE DICTIONARY The definitions below are derived from official public sources, including the National Institutes of Health [NIH] and the European Union [EU]. 1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine: A dopaminergic neurotoxic compound which produces irreversible clinical, chemical, and pathological alterations that mimic those found in Parkinson disease. [NIH] Abdomen: That portion of the body that lies between the thorax and the pelvis. [NIH] Abdominal: Having to do with the abdomen, which is the part of the body between the chest and the hips that contains the pancreas, stomach, intestines, liver, gallbladder, and other organs. [NIH] Abdominal Pain: Sensation of discomfort, distress, or agony in the abdominal region. [NIH] Aberrant: Wandering or deviating from the usual or normal course. [EU] Ablation: The removal of an organ by surgery. [NIH] Abscess: A localized, circumscribed collection of pus. [NIH] Absenteeism: Chronic absence from work or other duty. [NIH] Acatalasia: A rare autosomal recessive disorder resulting from the absence of catalase activity. Though usually asymptomatic, a syndrome of oral ulcerations and gangrene may be present. [NIH] Acceptor: A substance which, while normally not oxidized by oxygen or reduced by hydrogen, can be oxidized or reduced in presence of a substance which is itself undergoing oxidation or reduction. [NIH] Acetaldehyde: A colorless, flammable liquid used in the manufacture of acetic acid, perfumes, and flavors. It is also an intermediate in the metabolism of alcohol. It has a general narcotic action and also causes irritation of mucous membranes. Large doses may cause death from respiratory paralysis. [NIH] Acetaminophen: Analgesic antipyretic derivative of acetanilide. It has weak antiinflammatory properties and is used as a common analgesic, but may cause liver, blood cell, and kidney damage. [NIH] 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] Acetylcysteine: The N-acetyl derivative of cysteine. It is used as a mucolytic agent to reduce the viscosity of mucous secretions. It has also been shown to have antiviral effects in patients with HIV due to inhibition of viral stimulation by reactive oxygen intermediates. [NIH] Aclarubicin: An anthracycline antibiotic produced by Streptomyces galilaeus. It has potent antineoplastic activity, especially in the treatment of leukemias, with reduced cardiac toxicity in comparison to daunorubicin or doxorubicin. [NIH] Acne: A disorder of the skin marked by inflammation of oil glands and hair glands. [NIH]
246 Glutathione
Acne Vulgaris: A chronic disorder of the pilosebaceous apparatus associated with an increase in sebum secretion. It is characterized by open comedones (blackheads), closed comedones (whiteheads), and pustular nodules. The cause is unknown, but heredity and age are predisposing factors. [NIH] Actin: Essential component of the cell skeleton. [NIH] Action Potentials: The electric response of a nerve or muscle to its stimulation. [NIH] Acute leukemia: A rapidly progressing cancer of the blood-forming tissue (bone marrow). [NIH]
Acute lymphoblastic leukemia: ALL. A quickly progressing disease in which too many immature white blood cells called lymphoblasts are found in the blood and bone marrow. Also called acute lymphocytic leukemia. [NIH] Acute lymphocytic leukemia: ALL. A quickly progressing disease in which too many immature white blood cells called lymphoblasts are found in the blood and bone marrow. Also called acute lymphoblastic leukemia. [NIH] Acute myelogenous leukemia: AML. A quickly progressing disease in which too many immature blood-forming cells are found in the blood and bone marrow. Also called acute myeloid leukemia or acute nonlymphocytic leukemia. [NIH] Acute myeloid leukemia: AML. A quickly progressing disease in which too many immature blood-forming cells are found in the blood and bone marrow. Also called acute myelogenous leukemia or acute nonlymphocytic leukemia. [NIH] Acute nonlymphocytic leukemia: A quickly progressing disease in which too many immature blood-forming cells are found in the blood and bone marrow. Also called acute myeloid leukemia or acute myelogenous leukemia. [NIH] Acyl: Chemical signal used by bacteria to communicate. [NIH] 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] Adduct: Complex formed when a carcinogen combines with DNA or a protein. [NIH] Adduction: The rotation of an eye toward the midline (nasally). [NIH] Adenine: A purine base and a fundamental unit of adenine nucleotides. [NIH] 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] Adenosine Triphosphate: Adenosine 5'-(tetrahydrogen triphosphate). An adenine nucleotide containing three phosphate groups esterified to the sugar moiety. In addition to its crucial roles in metabolism adenosine triphosphate is a neurotransmitter. [NIH] Adenovirus: A group of viruses that cause respiratory tract and eye infections. Adenoviruses used in gene therapy are altered to carry a specific tumor-fighting gene. [NIH] Adenylate Cyclase: An enzyme of the lyase class that catalyzes the formation of cyclic AMP
Dictionary 247
and pyrophosphate from ATP. EC 4.6.1.1. [NIH] Adipose Tissue: Connective tissue composed of fat cells lodged in the meshes of areolar tissue. [NIH] Adjustment: The dynamic process wherein the thoughts, feelings, behavior, and biophysiological mechanisms of the individual continually change to adjust to the environment. [NIH] Adolescence: The period of life beginning with the appearance of secondary sex characteristics and terminating with the cessation of somatic growth. The years usually referred to as adolescence lie between 13 and 18 years of age. [NIH] Adrenal Cortex: The outer layer of the adrenal gland. It secretes mineralocorticoids, androgens, and glucocorticoids. [NIH] Adrenal Glands: Paired glands situated in the retroperitoneal tissues at the superior pole of each kidney. [NIH] Adrenergic: Activated by, characteristic of, or secreting epinephrine or substances with similar activity; the term is applied to those nerve fibres that liberate norepinephrine at a synapse when a nerve impulse passes, i.e., the sympathetic fibres. [EU] Adverse Effect: An unwanted side effect of treatment. [NIH] Aerobic: In biochemistry, reactions that need oxygen to happen or happen when oxygen is present. [NIH] Aerobic Metabolism: A chemical process in which oxygen is used to make energy from carbohydrates (sugars). Also known as aerobic respiration, oxidative metabolism, or cell respiration. [NIH] Aerobic Respiration: A chemical process in which oxygen is used to make energy from carbohydrates (sugars). Also known as oxidative metabolism, cell respiration, or aerobic metabolism. [NIH] Aerosol: A solution of a drug which can be atomized into a fine mist for inhalation therapy. [EU]
Affinity: 1. Inherent likeness or relationship. 2. A special attraction for a specific element, organ, or structure. 3. Chemical affinity; the force that binds atoms in molecules; the tendency of substances to combine by chemical reaction. 4. The strength of noncovalent chemical binding between two substances as measured by the dissociation constant of the complex. 5. In immunology, a thermodynamic expression of the strength of interaction between a single antigen-binding site and a single antigenic determinant (and thus of the stereochemical compatibility between them), most accurately applied to interactions among simple, uniform antigenic determinants such as haptens. Expressed as the association constant (K litres mole -1), which, owing to the heterogeneity of affinities in a population of antibody molecules of a given specificity, actually represents an average value (mean intrinsic association constant). 6. The reciprocal of the dissociation constant. [EU] Affinity Chromatography: In affinity chromatography, a ligand attached to a column binds specifically to the molecule to be purified. [NIH] Affinity Labels: Analogs of those substrates or compounds which bind naturally at the active sites of proteins, enzymes, antibodies, steroids, or physiological receptors. These analogs form a stable covalent bond at the binding site, thereby acting as inhibitors of the proteins or steroids. [NIH] Aflatoxins: A group of closely related toxic metabolites that are designated mycotoxins. They are produced by Aspergillus flavus and A. parasiticus. Members of the group include aflatoxin B1, aflatoxin B2, aflatoxin G1, aflatoxin G2, aflatoxin M1, and aflatoxin M2. [NIH]
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Agar: A complex sulfated polymer of galactose units, extracted from Gelidium cartilagineum, Gracilaria confervoides, and related red algae. It is used as a gel in the preparation of solid culture media for microorganisms, as a bulk laxative, in making emulsions, and as a supporting medium for immunodiffusion and immunoelectrophoresis. [NIH]
Age of Onset: The age or period of life at which a disease or the initial symptoms or manifestations of a disease appear in an individual. [NIH] Ageing: A physiological or morphological change in the life of an organism or its parts, generally irreversible and typically associated with a decline in growth and reproductive vigor. [NIH] Aggressiveness: The quality of being aggressive (= characterized by aggression; militant; enterprising; spreading with vigour; chemically active; variable and adaptable). [EU] 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] Air Pollutants: Substances which pollute the air. [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] Alcohol Dehydrogenase: An enzyme that catalyzes reversibly the final step of alcoholic fermentation by reducing an aldehyde to an alcohol. In the case of ethanol, acetaldehyde is reduced to ethanol in the presence of NADH and hydrogen. The enzyme is a zinc protein which acts on primary and secondary alcohols or hemiacetals. EC 1.1.1.1. [NIH] Aldehyde Dehydrogenase: An enzyme that oxidizes an aldehyde in the presence of NAD+ and water to an acid and NADH. EC 1.2.1.3. Before 1978, it was classified as EC 1.1.1.70. [NIH]
Aldehyde Reductase: An enzyme that catalyzes reversibly the oxidation of an aldose to an alditol. It possesses broad specificity for many aldoses. EC 1.1.1.21. [NIH] Aldehydes: Organic compounds containing a carbonyl group in the form -CHO. [NIH] Alfalfa: A deep-rooted European leguminous plant (Medicago sativa) widely grown for hay and forage. [NIH] Algorithms: A procedure consisting of a sequence of algebraic formulas and/or logical steps to calculate or determine a given task. [NIH] Alimentary: Pertaining to food or nutritive material, or to the organs of digestion. [EU] Alkaline: Having the reactions of an alkali. [EU] Alkaloid: A member of a large group of chemicals that are made by plants and have nitrogen in them. Some alkaloids have been shown to work against cancer. [NIH] Alkylate: To treat with an alkylating agent. [EU] Alkylating Agents: Highly reactive chemicals that introduce alkyl radicals into biologically
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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]
Alkylation: The covalent bonding of an alkyl group to an organic compound. It can occur by a simple addition reaction or by substitution of another functional group. [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] Allografts: A graft of tissue obtained from the body of another animal of the same species but with genotype differing from that of the recipient; tissue graft from a donor of one genotype to a host of another genotype with host and donor being members of the same species. [NIH] Allopurinol: A xanthine oxidase inhibitor that decreases uric acid production. [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] 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] Ambulatory Care: Health care services provided to patients on an ambulatory basis, rather than by admission to a hospital or other health care facility. The services may be a part of a hospital, augmenting its inpatient services, or may be provided at a free-standing facility. [NIH]
Ameliorated: A changeable condition which prevents the consequence of a failure or accident from becoming as bad as it otherwise would. [NIH] Ameliorating: A changeable condition which prevents the consequence of a failure or accident from becoming as bad as it otherwise would. [NIH] Amine: An organic compound containing nitrogen; any member of a group of chemical compounds formed from ammonia by replacement of one or more of the hydrogen atoms by organic (hydrocarbon) radicals. The amines are distinguished as primary, secondary, and tertiary, according to whether one, two, or three hydrogen atoms are replaced. The amines include allylamine, amylamine, ethylamine, methylamine, phenylamine, propylamine, and many other compounds. [EU] Amino Acid Sequence: The order of amino acids as they occur in a polypeptide chain. This is referred to as the primary structure of proteins. It is of fundamental importance in determining protein conformation. [NIH] Amino Acids: Organic compounds that generally contain an amino (-NH2) and a carboxyl (COOH) group. Twenty alpha-amino acids are the subunits which are polymerized to form
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proteins. [NIH] Amino Acids: Organic compounds that generally contain an amino (-NH2) and a carboxyl (COOH) group. Twenty alpha-amino acids are the subunits which are polymerized to form proteins. [NIH] Aminoethyl: A protease inhibitor. [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] Amputation: Surgery to remove part or all of a limb or appendage. [NIH] Amyloid: A general term for a variety of different proteins that accumulate as extracellular fibrils of 7-10 nm and have common structural features, including a beta-pleated sheet conformation and the ability to bind such dyes as Congo red and thioflavine (Kandel, Schwartz, and Jessel, Principles of Neural Science, 3rd ed). [NIH] Anaerobic: 1. Lacking molecular oxygen. 2. Growing, living, or occurring in the absence of molecular oxygen; pertaining to an anaerobe. [EU] Anaesthesia: Loss of feeling or sensation. Although the term is used for loss of tactile sensibility, or of any of the other senses, it is applied especially to loss of the sensation of pain, as it is induced to permit performance of surgery or other painful procedures. [EU] Anal: Having to do with the anus, which is the posterior opening of the large bowel. [NIH] Analgesic: An agent that alleviates pain without causing loss of consciousness. [EU] Analog: In chemistry, a substance that is similar, but not identical, to another. [NIH] Analogous: Resembling or similar in some respects, as in function or appearance, but not in origin or development;. [EU] Analytes: A component of a test sample the presence of which has to be demonstrated. The term "analyte" includes where appropriate formed from the analyte during the analyses. [NIH]
Anaphylatoxins: The family of peptides C3a, C4a, C5a, and C5a des-arginine produced in the serum during complement activation. They produce smooth muscle contraction, mast cell histamine release, affect platelet aggregation, and act as mediators of the local inflammatory process. The order of anaphylatoxin activity from strongest to weakest is C5a, C3a, C4a, and C5a des-arginine. The latter is the so-called "classical" anaphylatoxin but shows no spasmogenic activity though it contains some chemotactic ability. [NIH] Anaplasia: Loss of structural differentiation and useful function of neoplastic cells. [NIH] Anatomical: Pertaining to anatomy, or to the structure of the organism. [EU] Anemia: A reduction in the number of circulating erythrocytes or in the quantity of hemoglobin. [NIH] Anesthesia: A state characterized by loss of feeling or sensation. This depression of nerve function is usually the result of pharmacologic action and is induced to allow performance of surgery or other painful procedures. [NIH] Aneurysm: A sac formed by the dilatation of the wall of an artery, a vein, or the heart. [NIH] Angina: Chest pain that originates in the heart. [NIH] 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] 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
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procedures performed by catheterization. When reconstruction of an artery is performed surgically, it is called endarterectomy. [NIH] Animal model: An animal with a disease either the same as or like a disease in humans. Animal models are used to study the development and progression of diseases and to test new treatments before they are given to humans. Animals with transplanted human cancers or other tissues are called xenograft models. [NIH] Anions: Negatively charged atoms, radicals or groups of atoms which travel to the anode or positive pole during electrolysis. [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] 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] Anthracycline: A member of a family of anticancer drugs that are also antibiotics. [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]
Antibodies: Immunoglobulin molecules having a specific amino acid sequence by virtue of which they interact only with the antigen that induced their synthesis in cells of the lymphoid series (especially plasma cells), or with an antigen closely related to it. [NIH] Antibody: A type of protein made by certain white blood cells in response to a foreign substance (antigen). Each antibody can bind to only a specific antigen. The purpose of this binding is to help destroy the antigen. Antibodies can work in several ways, depending on the nature of the antigen. Some antibodies destroy antigens directly. Others make it easier for white blood cells to destroy the antigen. [NIH] Anticoagulant: A drug that helps prevent blood clots from forming. Also called a blood thinner. [NIH] Antidote: A remedy for counteracting a poison. [EU] Antiemetic: An agent that prevents or alleviates nausea and vomiting. Also antinauseant. [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] Antihypertensive: An agent that reduces high blood pressure. [EU]
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Anti-infective: An agent that so acts. [EU] Anti-inflammatory: Having to do with reducing inflammation. [NIH] Antimetabolite: A chemical that is very similar to one required in a normal biochemical reaction in cells. Antimetabolites can stop or slow down the reaction. [NIH] Antimicrobial: Killing microorganisms, or suppressing their multiplication or growth. [EU] Antineoplastic: Inhibiting or preventing the development of neoplasms, checking the maturation and proliferation of malignant cells. [EU] 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] Antipsychotic: Effective in the treatment of psychosis. Antipsychotic drugs (called also neuroleptic drugs and major tranquilizers) are a chemically diverse (including phenothiazines, thioxanthenes, butyrophenones, dibenzoxazepines, dibenzodiazepines, and diphenylbutylpiperidines) but pharmacologically similar class of drugs used to treat schizophrenic, paranoid, schizoaffective, and other psychotic disorders; acute delirium and dementia, and manic episodes (during induction of lithium therapy); to control the movement disorders associated with Huntington's chorea, Gilles de la Tourette's syndrome, and ballismus; and to treat intractable hiccups and severe nausea and vomiting. Antipsychotic agents bind to dopamine, histamine, muscarinic cholinergic, a-adrenergic, and serotonin receptors. Blockade of dopaminergic transmission in various areas is thought to be responsible for their major effects : antipsychotic action by blockade in the mesolimbic and mesocortical areas; extrapyramidal side effects (dystonia, akathisia, parkinsonism, and tardive dyskinesia) by blockade in the basal ganglia; and antiemetic effects by blockade in the chemoreceptor trigger zone of the medulla. Sedation and autonomic side effects (orthostatic hypotension, blurred vision, dry mouth, nasal congestion and constipation) are caused by blockade of histamine, cholinergic, and adrenergic receptors. [EU] Antipyretic: An agent that relieves or reduces fever. Called also antifebrile, antithermic and febrifuge. [EU] Antiseptic: A substance that inhibits the growth and development of microorganisms without necessarily killing them. [EU] Antiviral: Destroying viruses or suppressing their replication. [EU] Anus: The opening of the rectum to the outside of the body. [NIH] Anxiety: Persistent feeling of dread, apprehension, and impending disaster. [NIH] Aorta: The main trunk of the systemic arteries. [NIH] Apolipoproteins: The protein components of lipoproteins which remain after the lipids to which the proteins are bound have been removed. They play an important role in lipid transport and metabolism. [NIH] Apoptosis: One of the two mechanisms by which cell death occurs (the other being the pathological process of necrosis). Apoptosis is the mechanism responsible for the physiological deletion of cells and appears to be intrinsically programmed. It is characterized by distinctive morphologic changes in the nucleus and cytoplasm, chromatin cleavage at regularly spaced sites, and the endonucleolytic cleavage of genomic DNA (DNA fragmentation) at internucleosomal sites. This mode of cell death serves as a balance to mitosis in regulating the size of animal tissues and in mediating pathologic processes associated with tumor growth. [NIH]
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Aqueous: Having to do with water. [NIH] Aqueous fluid: Clear, watery fluid that flows between and nourishes the lens and the cornea; secreted by the ciliary processes. [NIH] Arachidonate 12-Lipoxygenase: An enzyme that catalyzes the oxidation of arachidonic acid to yield 12-hydroperoxyarachidonate (12-HPETE) which is itself rapidly converted by a peroxidase to 12-hydroxy-5,8,10,14-eicosatetraenoate (12-HETE). The 12-hydroperoxides are preferentially formed in platelets. EC 1.13.11.31. [NIH] Arachidonate 15-Lipoxygenase: An enzyme that catalyzes the oxidation of arachidonic acid to yield 15-hydroperoxyarachidonate (15-HPETE) which is rapidly converted to 15-hydroxy5,8,11,13-eicosatetraenoate (15-HETE). The 15-hydroperoxides are preferentially formed in neutrophils and lymphocytes. EC 1.13.11.33. [NIH] Arachidonate Lipoxygenases: Enzymes catalyzing the oxidation of arachidonic acid to hydroperoxyarachidonates (HPETES). These products are then rapidly converted by a peroxidase to hydroxyeicosatetraenoic acids (HETES). The positional specificity of the enzyme reaction varies from tissue to tissue. The final lipoxygenase pathway leads to the leukotrienes. EC 1.13.11.- . [NIH] 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] Arteriolosclerosis: Sclerosis and thickening of the walls of the smaller arteries (arterioles). Hyaline arteriolosclerosis, in which there is homogeneous pink hyaline thickening of the arteriolar walls, is associated with benign nephrosclerosis. Hyperplastic arteriolosclerosis, in which there is a concentric thickening with progressive narrowing of the lumina may be associated with malignant hypertension, nephrosclerosis, and scleroderma. [EU] Arteriosclerosis: Thickening and loss of elasticity of arterial walls. Atherosclerosis is the most common form of arteriosclerosis and involves lipid deposition and thickening of the intimal cell layers within arteries. Additional forms of arteriosclerosis involve calcification of the media of muscular arteries (Monkeberg medial calcific sclerosis) and thickening of the walls of small arteries or arterioles due to cell proliferation or hyaline deposition (arteriolosclerosis). [NIH] Arteriovenous: Both arterial and venous; pertaining to or affecting an artery and a vein. [EU] Asbestos: Fibrous incombustible mineral composed of magnesium and calcium silicates with or without other elements. It is relatively inert chemically and used in thermal insulation and fireproofing. Inhalation of dust causes asbestosis and later lung and gastrointestinal neoplasms. [NIH]
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Asbestosis: A lung disorder caused by constant inhalation of asbestos particles. [NIH] Ascites: Accumulation or retention of free fluid within the peritoneal cavity. [NIH] Ascorbic Acid: A six carbon compound related to glucose. It is found naturally in citrus fruits and many vegetables. Ascorbic acid is an essential nutrient in human diets, and necessary to maintain connective tissue and bone. Its biologically active form, vitamin C, functions as a reducing agent and coenzyme in several metabolic pathways. Vitamin C is considered an antioxidant. [NIH] Aspartate: A synthetic amino acid. [NIH] Asphyxia: A pathological condition caused by lack of oxygen, manifested in impending or actual cessation of life. [NIH] Assay: Determination of the amount of a particular constituent of a mixture, or of the biological or pharmacological potency of a drug. [EU] Astringent: Causing contraction, usually locally after topical application. [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] Astrocytoma: A tumor that begins in the brain or spinal cord in small, star-shaped cells called astrocytes. [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] Atmospheric Pressure: The pressure at any point in an atmosphere due solely to the weight of the atmospheric gases above the point concerned. [NIH] Atopic: Pertaining to an atopen or to atopy; allergic. [EU] Atrium: A chamber; used in anatomical nomenclature to designate a chamber affording entrance to another structure or organ. Usually used alone to designate an atrium of the heart. [EU] Atrophy: Decrease in the size of a cell, tissue, organ, or multiple organs, associated with a variety of pathological conditions such as abnormal cellular changes, ischemia, malnutrition, or hormonal changes. [NIH] Attenuated: Strain with weakened or reduced virulence. [NIH] Attenuation: Reduction of transmitted sound energy or its electrical equivalent. [NIH] Auditory: Pertaining to the sense of hearing. [EU] Aura: A subjective sensation or motor phenomenon that precedes and marks the of a paroxysmal attack, such as an epileptic attack on set. [EU] Autoimmune disease: A condition in which the body recognizes its own tissues as foreign and directs an immune response against them. [NIH]
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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] Autopsy: Postmortem examination of the body. [NIH] Auxin: A natural organic compound formed in actively growing parts of plants, particularly in the growing points of shoots, which in minute concentrations regulates cell expansion and other developmental processes. [NIH] Axillary: Pertaining to the armpit area, including the lymph nodes that are located there. [NIH]
Axons: Nerve fibers that are capable of rapidly conducting impulses away from the neuron cell body. [NIH] Azithromycin: A semi-synthetic macrolide antibiotic structurally related to erythromycin. It has been used in the treatment of Mycobacterium avium intracellulare infections, toxoplasmosis, and cryptosporidiosis. [NIH] 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 Physiology: Physiological processes and activities of bacteria. [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] 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] Benign: Not cancerous; does not invade nearby tissue or spread to other parts of the body. [NIH]
Benign tumor: A noncancerous growth that does not invade nearby tissue or spread to other parts of the body. [NIH]
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Benzoic Acid: A fungistatic compound that is widely used as a food preservative. It is conjugated to glycine in the liver and excreted as hippuric acid. [NIH] Benzoyl Peroxide: A peroxide derivative that has been used topically for burns and as a dermatologic agent in the treatment of acne and poison ivy. It is used also as a bleach in the food industry. [NIH] Beta Rays: A stream of positive or negative electrons ejected with high energy from a disintegrating atomic nucleus; most biomedically used isotopes emit negative particles (electrons or negatrons, rather than positrons). Cathode rays are low-energy negative electrons produced in cathode ray tubes, also called television tubes or oscilloscopes. [NIH] Beta-Galactosidase: A group of enzymes that catalyzes the hydrolysis of terminal, nonreducing beta-D-galactose residues in beta-galactosides. Deficiency of beta-Galactosidase A1 may cause gangliodisosis GM1. EC 3.2.1.23. [NIH] Beta-pleated: Particular three-dimensional pattern of amyloidoses. [NIH] 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 Pigments: Pigments that give a characteristic color to bile including: bilirubin, biliverdine, and bilicyanin. [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] Bioavailability: The degree to which a drug or other substance becomes available to the target tissue after administration. [EU] Biochemical: Relating to biochemistry; characterized by, produced by, or involving chemical reactions in living organisms. [EU] Biochemical reactions: In living cells, chemical reactions that help sustain life and allow cells to grow. [NIH] Biogenesis: The origin of life. It includes studies of the potential basis for life in organic compounds but excludes studies of the development of altered forms of life through mutation and natural selection, which is evolution. [NIH] Biological Markers: Measurable and quantifiable biological parameters (e.g., specific enzyme concentration, specific hormone concentration, specific gene phenotype distribution in a population, presence of biological substances) which serve as indices for health- and physiology-related assessments, such as disease risk, psychiatric disorders, environmental exposure and its effects, disease diagnosis, metabolic processes, substance abuse, pregnancy, cell line development, epidemiologic studies, etc. [NIH] Biological response modifier: BRM. A substance that stimulates the body's response to infection and disease. [NIH] Biological therapy: Treatment to stimulate or restore the ability of the immune system to fight infection and disease. Also used to lessen side effects that may be caused by some
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cancer treatments. Also known as immunotherapy, biotherapy, or biological response modifier (BRM) therapy. [NIH] Biomarkers: Substances sometimes found in an increased amount in the blood, other body fluids, or tissues and that may suggest the presence of some types of cancer. Biomarkers include CA 125 (ovarian cancer), CA 15-3 (breast cancer), CEA (ovarian, lung, breast, pancreas, and GI tract cancers), and PSA (prostate cancer). Also called tumor markers. [NIH] Biomolecular: A scientific field at the interface between advanced computing and biotechnology. [NIH] Bioreactors: Tools or devices for generating products using the synthetic or chemical conversion capacity of a biological system. They can be classical fermentors, cell culture perfusion systems, or enzyme bioreactors. For production of proteins or enzymes, recombinant microorganisms such as bacteria, mammalian cells, or insect or plant cells are usually chosen. [NIH] Biosynthesis: The building up of a chemical compound in the physiologic processes of a living organism. [EU] Biotechnology: Body of knowledge related to the use of organisms, cells or cell-derived constituents for the purpose of developing products which are technically, scientifically and clinically useful. Alteration of biologic function at the molecular level (i.e., genetic engineering) is a central focus; laboratory methods used include transfection and cloning technologies, sequence and structure analysis algorithms, computer databases, and gene and protein structure function analysis and prediction. [NIH] Biotic: Pertaining to living organisms in their ecological rather than their physiological relations. [NIH] Biotransformation: The chemical alteration of an exogenous substance by or in a biological system. The alteration may inactivate the compound or it may result in the production of an active metabolite of an inactive parent compound. The alteration may be either nonsynthetic (oxidation-reduction, hydrolysis) or synthetic (glucuronide formation, sulfate conjugation, acetylation, methylation). This also includes metabolic detoxication and clearance. [NIH] 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] Blasts: Immature blood cells. [NIH] Blennorrhoea: A general term including any inflammatory process of the external eye which gives a mucoid discharge, more exactly, a discharge of mucus. [NIH] Blood Cell Count: A count of the number of leukocytes and erythrocytes per unit volume in a sample of venous blood. A complete blood count (CBC) also includes measurement of the hemoglobin, hematocrit, and erythrocyte indices. [NIH] Blood Coagulation: The process of the interaction of blood coagulation factors that results in an insoluble fibrin clot. [NIH] Blood Glucose: Glucose in blood. [NIH] Blood Platelets: Non-nucleated disk-shaped cells formed in the megakaryocyte and found in the blood of all mammals. They are mainly involved in blood coagulation. [NIH]
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Blood pressure: The pressure of blood against the walls of a blood vessel or heart chamber. Unless there is reference to another location, such as the pulmonary artery or one of the heart chambers, it refers to the pressure in the systemic arteries, as measured, for example, in the forearm. [NIH] Blood vessel: A tube in the body through which blood circulates. Blood vessels include a network of arteries, arterioles, capillaries, venules, and veins. [NIH] Blood Volume: Volume of circulating blood. It is the sum of the plasma volume and erythrocyte volume. [NIH] Blood-Brain Barrier: Specialized non-fenestrated tightly-joined endothelial cells (tight junctions) that form a transport barrier for certain substances between the cerebral capillaries and the brain tissue. [NIH] Blot: To transfer DNA, RNA, or proteins to an immobilizing matrix such as nitrocellulose. [NIH]
Blotting, Western: Identification of proteins or peptides that have been electrophoretically separated by blotting and transferred to strips of nitrocellulose paper. The blots are then detected by radiolabeled antibody probes. [NIH] 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 period of time. Also called bolus. [NIH] Bone Marrow: The soft tissue filling the cavities of bones. Bone marrow exists in two types, yellow and red. Yellow marrow is found in the large cavities of large bones and consists mostly of fat cells and a few primitive blood cells. Red marrow is a hematopoietic tissue and is the site of production of erythrocytes and granular leukocytes. Bone marrow is made up of a framework of connective tissue containing branching fibers with the frame being filled with marrow cells. [NIH] Bone Marrow Cells: Cells contained in the bone marrow including fat cells, stromal cells, megakaryocytes, and the immediate precursors of most blood cells. [NIH] Bone Marrow Transplantation: The transference of bone marrow from one human or animal to another. [NIH] 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] Boron Neutron Capture Therapy: A technique for the treatment of neoplasms, especially gliomas and melanomas in which boron-10, an isotope, is introduced into the target cells followed by irradiation with thermal neutrons. [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] 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
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permeability. Bradykinin is also released from mast cells during asthma attacks, from gut walls as a gastrointestinal vasodilator, from damaged tissues as a pain signal, and may be a neurotransmitter. [NIH] Brain Hypoxia: Lack of oxygen leading to unconsciousness. [NIH] Brain Infarction: The formation of an area of necrosis in the brain, including the cerebral hemispheres (cerebral infarction), thalami, basal ganglia, brain stem (brain stem infarctions), or cerebellum secondary to an insufficiency of arterial or venous blood flow. [NIH] Brain Ischemia: Localized reduction of blood flow to brain tissue due to arterial obtruction or systemic hypoperfusion. This frequently occurs in conjuction with brain hypoxia. Prolonged ischemia is associated with brain infarction. [NIH] Brain Stem: The part of the brain that connects the cerebral hemispheres with the spinal cord. It consists of the mesencephalon, pons, and medulla oblongata. [NIH] Branch: Most commonly used for branches of nerves, but applied also to other structures. [NIH]
Breakdown: A physical, metal, or nervous collapse. [NIH] 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] Bromine: A halogen with the atomic symbol Br, atomic number 36, and atomic weight 79.904. It is a volatile reddish-brown liquid that gives off suffocating vapors, is corrosive to the skin, and may cause severe gastroenteritis if ingested. [NIH] Bronchi: The larger air passages of the lungs arising from the terminal bifurcation of the trachea. [NIH] Bronchial: Pertaining to one or more bronchi. [EU] Bronchiseptica: A small, gram-negative, motile bacillus. A normal inhabitant of the respiratory tract in man, dogs, and pigs, but is also associated with canine infectious tracheobronchitis and atrophic rhinitis in pigs. [NIH] Bronchitis: Inflammation (swelling and reddening) of the bronchi. [NIH] Burns: Injuries to tissues caused by contact with heat, steam, chemicals (burns, chemical), electricity (burns, electric), or the like. [NIH] Burns, Electric: Burns produced by contact with electric current or from a sudden discharge of electricity. [NIH] Busulfan: An anticancer drug that belongs to the family of drugs called alkylating agents. [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] Calcification: Deposits of calcium in the tissues of the breast. Calcification in the breast can be seen on a mammogram, but cannot be detected by touch. There are two types of breast calcification, macrocalcification and microcalcification. Macrocalcifications are large deposits and are usually not related to cancer. Microcalcifications are specks of calcium that may be found in an area of rapidly dividing cells. Many microcalcifications clustered together may be a sign of cancer. [NIH]
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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 Chloride: A salt used to replenish calcium levels, as an acid-producing diuretic, and as an antidote for magnesium poisoning. [NIH] Calmodulin: A heat-stable, low-molecular-weight activator protein found mainly in the brain and heart. The binding of calcium ions to this protein allows this protein to bind to cyclic nucleotide phosphodiesterases and to adenyl cyclase with subsequent activation. Thereby this protein modulates cyclic AMP and cyclic GMP levels. [NIH] 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] Canonical: A particular nucleotide sequence in which each position represents the base more often found when many actual sequences of a given class of genetic elements are compared. [NIH] Capillary: Any one of the minute vessels that connect the arterioles and venules, forming a network in nearly all parts of the body. Their walls act as semipermeable membranes for the interchange of various substances, including fluids, between the blood and tissue fluid; called also vas capillare. [EU] Capillary Permeability: Property of blood capillary walls that allows for the selective exchange of substances. Small lipid-soluble molecules such as carbon dioxide and oxygen move freely by diffusion. Water and water-soluble molecules cannot pass through the endothelial walls and are dependent on microscopic pores. These pores show narrow areas (tight junctions) which may limit large molecule movement. [NIH] Capsid: The outer protein protective shell of a virus, which protects the viral nucleic acid. [NIH]
Capsules: Hard or soft soluble containers used for the oral administration of medicine. [NIH] Captopril: A potent and specific inhibitor of peptidyl-dipeptidase A. It blocks the conversion of angiotensin I to angiotensin II, a vasoconstrictor and important regulator of arterial blood pressure. Captopril acts to suppress the renin-angiotensin system and inhibits pressure responses to exogenous angiotensin. [NIH] Carbohydrate: An aldehyde or ketone derivative of a polyhydric alcohol, particularly of the pentahydric and hexahydric alcohols. They are so named because the hydrogen and oxygen are usually in the proportion to form water, (CH2O)n. The most important carbohydrates are the starches, sugars, celluloses, and gums. They are classified into mono-, di-, tri-, polyand heterosaccharides. [EU] Carbon Dioxide: A colorless, odorless gas that can be formed by the body and is necessary for the respiration cycle of plants and animals. [NIH] Carboplatin: An organoplatinum compound that possesses antineoplastic activity. [NIH] Carboxy: Cannabinoid. [NIH] Carboxy-terminal: The end of any polypeptide or protein that bears a free carboxyl group. [NIH]
Carcinogen: Any substance that causes cancer. [NIH] Carcinogenesis: The process by which normal cells are transformed into cancer cells. [NIH]
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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] 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] Cardiovascular System: The heart and the blood vessels by which blood is pumped and circulated through the body. [NIH] Carnitine: Constituent of striated muscle and liver. It is used therapeutically to stimulate gastric and pancreatic secretions and in the treatment of hyperlipoproteinemias. [NIH] Carotene: The general name for a group of pigments found in green, yellow, and leafy vegetables, and yellow fruits. The pigments are fat-soluble, unsaturated aliphatic hydrocarbons functioning as provitamins and are converted to vitamin A through enzymatic processes in the intestinal wall. [NIH] Carrier Proteins: Transport proteins that carry specific substances in the blood or across cell membranes. [NIH] Case report: A detailed report of the diagnosis, treatment, and follow-up of an individual patient. Case reports also contain some demographic information about the patient (for example, age, gender, ethnic origin). [NIH] Case series: A group or series of case reports involving patients who were given similar treatment. Reports of case series usually contain detailed information about the individual patients. This includes demographic information (for example, age, gender, ethnic origin) and information on diagnosis, treatment, response to treatment, and follow-up after treatment. [NIH] 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] Catalase: An oxidoreductase that catalyzes the conversion of hydrogen peroxide to water and oxygen. It is present in many animal cells. A deficiency of this enzyme results in acatalasia. EC 1.11.1.6. [NIH] Catalytic Domain: The region of an enzyme that interacts with its substrate to cause the enzymatic reaction. [NIH] Cataract: An opacity, partial or complete, of one or both eyes, on or in the lens or capsule, especially an opacity impairing vision or causing blindness. The many kinds of cataract are classified by their morphology (size, shape, location) or etiology (cause and time of occurrence). [EU] Catechol: A chemical originally isolated from a type of mimosa tree. Catechol is used as an astringent, an antiseptic, and in photography, electroplating, and making other chemicals. It can also be man-made. [NIH] Catecholamine: A group of chemical substances manufactured by the adrenal medulla and secreted during physiological stress. [NIH]
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Catheterization: Use or insertion of a tubular device into a duct, blood vessel, hollow organ, or body cavity for injecting or withdrawing fluids for diagnostic or therapeutic purposes. It differs from intubation in that the tube here is used to restore or maintain patency in obstructions. [NIH] Cathode: An electrode, usually an incandescent filament of tungsten, which emits electrons in an X-ray tube. [NIH] Cations: Postively charged atoms, radicals or groups of atoms which travel to the cathode or negative pole during electrolysis. [NIH] Caudal: Denoting a position more toward the cauda, or tail, than some specified point of reference; same as inferior, in human anatomy. [EU] Causal: Pertaining to a cause; directed against a cause. [EU] Cause of Death: Factors which produce cessation of all vital bodily functions. They can be analyzed from an epidemiologic viewpoint. [NIH] Caustic: An escharotic or corrosive agent. Called also cauterant. [EU] 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 Count: A count of the number of cells of a specific kind, usually measured per unit volume of sample. [NIH] Cell Cycle: The complex series of phenomena, occurring between the end of one cell division and the end of the next, by which cellular material is divided between daughter cells. [NIH] Cell Death: The termination of the cell's ability to carry out vital functions such as metabolism, growth, reproduction, responsiveness, and adaptability. [NIH] Cell Differentiation: Progressive restriction of the developmental potential and increasing specialization of function which takes place during the development of the embryo and leads to the formation of specialized cells, tissues, and organs. [NIH] Cell Division: The fission of a cell. [NIH] Cell Extracts: Preparations of cell constituents or subcellular materials, isolates, or substances. [NIH] Cell membrane: Cell membrane = plasma membrane. The structure enveloping a cell, enclosing the cytoplasm, and forming a selective permeability barrier; it consists of lipids, proteins, and some carbohydrates, the lipids thought to form a bilayer in which integral proteins are embedded to varying degrees. [EU] Cell Membrane Permeability: A quality of cell membranes which permits the passage of solvents and solutes into and out of cells. [NIH] Cell proliferation: An increase in the number of cells as a result of cell growth and cell division. [NIH] Cell Respiration: The metabolic process of all living cells (animal and plant) in which oxygen is used to provide a source of energy for the cell. [NIH] Cell Size: The physical dimensions of a cell. It refers mainly to changes in dimensions correlated with physiological or pathological changes in cells. [NIH] Cell Survival: The span of viability of a cell characterized by the capacity to perform certain functions such as metabolism, growth, reproduction, some form of responsiveness, and adaptability. [NIH] Cellular metabolism: The sum of all chemical changes that take place in a cell through
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which energy and basic components are provided for essential processes, including the synthesis of new molecules and the breakdown and removal of others. [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] Cerebellum: Part of the metencephalon that lies in the posterior cranial fossa behind the brain stem. It is concerned with the coordination of movement. [NIH] Cerebral: Of or pertaining of the cerebrum or the brain. [EU] Cerebral hemispheres: The two halves of the cerebrum, the part of the brain that controls muscle functions of the body and also controls speech, emotions, reading, writing, and learning. The right hemisphere controls muscle movement on the left side of the body, and the left hemisphere controls muscle movement on the right side of the body. [NIH] Cerebral Infarction: The formation of an area of necrosis in the cerebrum caused by an insufficiency of arterial or venous blood flow. Infarcts of the cerebrum are generally classified by hemisphere (i.e., left vs. right), lobe (e.g., frontal lobe infarction), arterial distribution (e.g., infarction, anterior cerebral artery), and etiology (e.g., embolic infarction). [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] Cerebrovascular: Pertaining to the blood vessels of the cerebrum, or brain. [EU] Cerebrovascular Disorders: A broad category of disorders characterized by impairment of blood flow in the arteries and veins which supply the brain. These include cerebral infarction; brain ischemia; hypoxia, brain; intracranial embolism and thrombosis; intracranial arteriovenous malformations; and vasculitis, central nervous system. In common usage, the term cerebrovascular disorders is not limited to conditions that affect the cerebrum, but refers to vascular disorders of the entire brain including the diencephalon; brain stem; and cerebellum. [NIH] Cerebrum: The largest part of the brain. It is divided into two hemispheres, or halves, called the cerebral hemispheres. The cerebrum controls muscle functions of the body and also controls speech, emotions, reading, writing, and learning. [NIH] Cervical: Relating to the neck, or to the neck of any organ or structure. Cervical lymph nodes are located in the neck; cervical cancer refers to cancer of the uterine cervix, which is the lower, narrow end (the "neck") of the uterus. [NIH] Cervix: The lower, narrow end of the uterus that forms a canal between the uterus and
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vagina. [NIH] Character: In current usage, approximately equivalent to personality. The sum of the relatively fixed personality traits and habitual modes of response of an individual. [NIH] Chelation: Combination with a metal in complexes in which the metal is part of a ring. [EU] 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] Chemotherapeutics: Noun plural but singular or plural in constructions : chemotherapy. [EU]
Chemotherapy: Treatment with anticancer drugs. [NIH] Chlorambucil: An anticancer drug that belongs to the family of drugs called alkylating agents. [NIH] Chlorine: A greenish-yellow, diatomic gas that is a member of the halogen family of elements. It has the atomic symbol Cl, atomic number 17, and atomic weight 70.906. It is a powerful irritant that can cause fatal pulmonary edema. Chlorine is used in manufacturing, as a reagent in synthetic chemistry, for water purification, and in the production of chlorinated lime, which is used in fabric bleaching. [NIH] Chlorine Compounds: Inorganic compounds that contain chlorine as an integral part of the molecule. [NIH] Chlorophyll: Porphyrin derivatives containing magnesium that act to convert light energy in photosynthetic organisms. [NIH] Chloroplasts: Plant cell inclusion bodies that contain the photosynthetic pigment chlorophyll, which is associated with the membrane of thylakoids. Chloroplasts occur in cells of leaves and young stems of higher plants. [NIH] Chlorpromazine: The prototypical phenothiazine antipsychotic drug. Like the other drugs in this class chlorpromazine's antipsychotic actions are thought to be due to long-term adaptation by the brain to blocking dopamine receptors. Chlorpromazine has several other actions and therapeutic uses, including as an antiemetic and in the treatment of intractable hiccup. [NIH] Cholesterol: The principal sterol of all higher animals, distributed in body tissues, especially the brain and spinal cord, and in animal fats and oils. [NIH] Cholesterol Esters: Fatty acid esters of cholesterol which constitute about two-thirds of the cholesterol in the plasma. The accumulation of cholesterol esters in the arterial intima is a characteristic feature of atherosclerosis. [NIH] Choline: A basic constituent of lecithin that is found in many plants and animal organs. It is important as a precursor of acetylcholine, as a methyl donor in various metabolic processes, and in lipid metabolism. [NIH] Cholinergic: Resembling acetylcholine in pharmacological action; stimulated by or releasing acetylcholine or a related compound. [EU] Chondroitin sulfate: The major glycosaminoglycan (a type of sugar molecule) in cartilage. [NIH]
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Choroid: The thin, highly vascular membrane covering most of the posterior of the eye between the retina and sclera. [NIH] Chromatin: The material of chromosomes. It is a complex of DNA, histones, and nonhistone proteins (chromosomal proteins, non-histone) found within the nucleus of a cell. [NIH] 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] Chromium Compounds: Inorganic compounds that contain chromium as an integral part of the molecule. [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 Obstructive Pulmonary Disease: Collective term for chronic bronchitis and emphysema. [NIH] Chronic renal: Slow and progressive loss of kidney function over several years, often resulting in end-stage renal disease. People with end-stage renal disease need dialysis or transplantation to replace the work of the kidneys. [NIH] Chylomicrons: A class of lipoproteins that carry dietary cholesterol and triglycerides from the small intestines to the tissues. [NIH] Ciliary: Inflammation or infection of the glands of the margins of the eyelids. [NIH] Ciliary Arteries: Three groups of arteries found in the eye which supply the iris, pupil, sclera, conjunctiva, and the muscles of the iris. [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] CIS: Cancer Information Service. The CIS is the National Cancer Institute's link to the public, interpreting and explaining research findings in a clear and understandable manner, and providing personalized responses to specific questions about cancer. Access the CIS by calling 1-800-4-CANCER, or by using the Web site at http://cis.nci.nih.gov. [NIH] Cisplatin: An inorganic and water-soluble platinum complex. After undergoing hydrolysis, it reacts with DNA to produce both intra and interstrand crosslinks. These crosslinks appear to impair replication and transcription of DNA. The cytotoxicity of cisplatin correlates with cellular arrest in the G2 phase of the cell cycle. [NIH] Citric Acid: A key intermediate in metabolism. It is an acid compound found in citrus fruits. The salts of citric acid (citrates) can be used as anticoagulants due to their calcium chelating ability. [NIH] Citrus: Any tree or shrub of the Rue family or the fruit of these plants. [NIH] Clamp: A u-shaped steel rod used with a pin or wire for skeletal traction in the treatment of
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certain fractures. [NIH] Clear cell carcinoma: A rare type of tumor of the female genital tract in which the inside of the cells looks clear when viewed under a microscope. [NIH] Clinical Medicine: The study and practice of medicine by direct examination of the patient. [NIH]
Clinical study: A research study in which patients receive treatment in a clinic or other medical facility. Reports of clinical studies can contain results for single patients (case reports) or many patients (case series or clinical trials). [NIH] Clinical trial: A research study that tests how well new medical treatments or other interventions work in people. Each study is designed to test new methods of screening, prevention, diagnosis, or treatment of a disease. [NIH] Clitoral: Pertaining to the clitoris. [EU] Clone: The term "clone" has acquired a new meaning. It is applied specifically to the bits of inserted foreign DNA in the hybrid molecules of the population. Each inserted segment originally resided in the DNA of a complex genome amid millions of other DNA segment. [NIH]
Cloning: The production of a number of genetically identical individuals; in genetic engineering, a process for the efficient replication of a great number of identical DNA molecules. [NIH] Coagulation: 1. The process of clot formation. 2. In colloid chemistry, the solidification of a sol into a gelatinous mass; an alteration of a disperse phase or of a dissolved solid which causes the separation of the system into a liquid phase and an insoluble mass called the clot or curd. Coagulation is usually irreversible. 3. In surgery, the disruption of tissue by physical means to form an amorphous residuum, as in electrocoagulation and photocoagulation. [EU] Coal: A natural fuel formed by partial decomposition of vegetable matter under certain environmental conditions. [NIH] 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] Cochlear Duct: Spiral tube in the bony canal of the cochlea, lying on its outer wall between the scala vestibuli and scala tympani. [NIH] Codon: A set of three nucleotides in a protein coding sequence that specifies individual amino acids or a termination signal (codon, terminator). Most codons are universal, but some organisms do not produce the transfer RNAs (RNA, transfer) complementary to all codons. These codons are referred to as unassigned codons (codons, nonsense). [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] Cohort Studies: Studies in which subsets of a defined population are identified. These groups may or may not be exposed to factors hypothesized to influence the probability of the occurrence of a particular disease or other outcome. Cohorts are defined populations which, as a whole, are followed in an attempt to determine distinguishing subgroup characteristics. [NIH]
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Colchicine: A major alkaloid from Colchicum autumnale L. and found also in other Colchicum species. Its primary therapeutic use is in the treatment of gout, but it has been used also in the therapy of familial Mediterranean fever (periodic disease). [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] 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] Colony-Stimulating Factors: Glycoproteins found in a subfraction of normal mammalian plasma and urine. They stimulate the proliferation of bone marrow cells in agar cultures and the formation of colonies of granulocytes and/or macrophages. The factors include interleukin-3 (IL-3), granulocyte colony-stimulating factor (G-CSF), macrophage colonystimulating factor (M-CSF), and granulocyte-macrophage colony-stimulating factor (GMCSF). [NIH] 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] Colostrum: The thin, yellow, serous fluid secreted by the mammary glands during pregnancy and immediately postpartum before lactation begins. It consists of immunologically active substances, white blood cells, water, protein, fat, and carbohydrates. [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] Compacta: Part of substantia nigra. [NIH] Competency: The capacity of the bacterium to take up DNA from its surroundings. [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
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lower-case letter suffixes, e.g., C3a. Inactivated fragments may be designated with the suffix 'i', e.g. C3bi. Activated components or complexes with biological activity are designated by a bar over the symbol e.g. C1 or C4b,2a. The classic pathway is activated by the binding of C1 to classic pathway activators, primarily antigen-antibody complexes containing IgM, IgG1, IgG3; C1q binds to a single IgM molecule or two adjacent IgG molecules. The alternative pathway can be activated by IgA immune complexes and also by nonimmunologic materials including bacterial endotoxins, microbial polysaccharides, and cell walls. Activation of the classic pathway triggers an enzymatic cascade involving C1, C4, C2 and C3; activation of the alternative pathway triggers a cascade involving C3 and factors B, D and P. Both result in the cleavage of C5 and the formation of the membrane attack complex. Complement activation also results in the formation of many biologically active complement fragments that act as anaphylatoxins, opsonins, or chemotactic factors. [EU] Complementary and alternative medicine: CAM. Forms of treatment that are used in addition to (complementary) or instead of (alternative) standard treatments. These practices are not considered standard medical approaches. CAM includes dietary supplements, megadose vitamins, herbal preparations, special teas, massage therapy, magnet therapy, spiritual healing, and meditation. [NIH] Complementary medicine: Practices not generally recognized by the medical community as standard or conventional medical approaches and used to enhance or complement the standard treatments. Complementary medicine includes the taking of dietary supplements, megadose vitamins, and herbal preparations; the drinking of special teas; and practices such as massage therapy, magnet therapy, spiritual healing, and meditation. [NIH] Complementation: The production of a wild-type phenotype when two different mutations are combined in a diploid or a heterokaryon and tested in trans-configuration. [NIH] Complete remission: The disappearance of all signs of cancer. Also called a complete response. [NIH] Computational Biology: A field of biology concerned with the development of techniques for the collection and manipulation of biological data, and the use of such data to make biological discoveries or predictions. This field encompasses all computational methods and theories applicable to molecular biology and areas of computer-based techniques for solving biological problems including manipulation of models and datasets. [NIH] Conception: The onset of pregnancy, marked by implantation of the blastocyst; the formation of a viable zygote. [EU] Concomitant: Accompanying; accessory; joined with another. [EU] Cones: One type of specialized light-sensitive cells (photoreceptors) in the retina that provide sharp central vision and color vision. [NIH] Conjugated: Acting or operating as if joined; simultaneous. [EU] Conjugation: 1. The act of joining together or the state of being conjugated. 2. A sexual process seen in bacteria, ciliate protozoa, and certain fungi in which nuclear material is exchanged during the temporary fusion of two cells (conjugants). In bacterial genetics a form of sexual reproduction in which a donor bacterium (male) contributes some, or all, of its DNA (in the form of a replicated set) to a recipient (female) which then incorporates differing genetic information into its own chromosome by recombination and passes the recombined set on to its progeny by replication. In ciliate protozoa, two conjugants of separate mating types exchange micronuclear material and then separate, each now being a fertilized cell. In certain fungi, the process involves fusion of two gametes, resulting in union of their nuclei and formation of a zygote. 3. In chemistry, the joining together of two compounds to produce another compound, such as the combination of a toxic product with
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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] Connective Tissue: Tissue that supports and binds other tissues. It consists of connective tissue cells embedded in a large amount of extracellular matrix. [NIH] Connective Tissue: Tissue that supports and binds other tissues. It consists of connective tissue cells embedded in a large amount of extracellular matrix. [NIH] Connective Tissue Cells: A group of cells that includes fibroblasts, cartilage cells, adipocytes, smooth muscle cells, and bone cells. [NIH] Consciousness: Sense of awareness of self and of the environment. [NIH] Constitutional: 1. Affecting the whole constitution of the body; not local. 2. Pertaining to the constitution. [EU] Constriction: The act of constricting. [NIH] Constriction, Pathologic: The condition of an anatomical structure's being constricted beyond normal dimensions. [NIH] Consultation: A deliberation between two or more physicians concerning the diagnosis and the proper method of treatment in a case. [NIH] Consumption: Pulmonary tuberculosis. [NIH] Contamination: The soiling or pollution by inferior material, as by the introduction of organisms into a wound, or sewage into a stream. [EU] Contractility: Capacity for becoming short in response to a suitable stimulus. [EU] Contraindications: Any factor or sign that it is unwise to pursue a certain kind of action or treatment, e. g. giving a general anesthetic to a person with pneumonia. [NIH] Contralateral: Having to do with the opposite side of the body. [NIH] Control group: In a clinical trial, the group that does not receive the new treatment being studied. This group is compared to the group that receives the new treatment, to see if the new treatment works. [NIH] Controlled study: An experiment or clinical trial that includes a comparison (control) group. [NIH]
Coordination: Muscular or motor regulation or the harmonious cooperation of muscles or groups of muscles, in a complex action or series of actions. [NIH] Cornea: The transparent part of the eye that covers the iris and the pupil and allows light to enter the inside. [NIH] Corneum: The superficial layer of the epidermis containing keratinized cells. [NIH] Coronary: Encircling in the manner of a crown; a term applied to vessels; nerves, ligaments, etc. The term usually denotes the arteries that supply the heart muscle and, by extension, a pathologic involvement of them. [EU] Coronary heart disease: A type of heart disease caused by narrowing of the coronary 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]
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Corpus: The body of the uterus. [NIH] Cortex: The outer layer of an organ or other body structure, as distinguished from the internal substance. [EU] Cortical: Pertaining to or of the nature of a cortex or bark. [EU] Corticosteroids: Hormones that have antitumor activity in lymphomas and lymphoid leukemias; in addition, corticosteroids (steroids) may be used for hormone replacement and for the management of some of the complications of cancer and its treatment. [NIH] Cortisol: A steroid hormone secreted by the adrenal cortex as part of the body's response to stress. [NIH] Cranial: Pertaining to the cranium, or to the anterior (in animals) or superior (in humans) end of the body. [EU] Craniocerebral Trauma: Traumatic injuries involving the cranium and intracranial structures (i.e., brain; cranial nerves; meninges; and other structures). Injuries may be classified by whether or not the skull is penetrated (i.e., penetrating vs. nonpenetrating) or whether there is an associated hemorrhage. [NIH] Creatine: An amino acid that occurs in vertebrate tissues and in urine. In muscle tissue, creatine generally occurs as phosphocreatine. Creatine is excreted as creatinine in the urine. [NIH]
Creatine Kinase: A transferase that catalyzes formation of phosphocreatine from ATP + creatine. The reaction stores ATP energy as phosphocreatine. Three cytoplasmic isoenzymes have been identified in human tissues: MM from skeletal muscle, MB from myocardial tissue, and BB from nervous tissue as well as a mitochondrial isoenzyme. Macro-creatine kinase refers to creatine kinase complexed with other serum proteins. EC 2.7.3.2. [NIH] Creatinine: A compound that is excreted from the body in urine. Creatinine levels are measured to monitor kidney function. [NIH] Critical Care: Health care provided to a critically ill patient during a medical emergency or crisis. [NIH] Cross-Sectional Studies: Studies in which the presence or absence of disease or other health-related variables are determined in each member of the study population or in a representative sample at one particular time. This contrasts with longitudinal studies which are followed over a period of time. [NIH] Cryptosporidiosis: Parasitic intestinal infection with severe diarrhea caused by a protozoan, Cryptosporidium. It occurs in both animals and humans. [NIH] Crystallization: The formation of crystals; conversion to a crystalline form. [EU] 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] Cumulative Trauma Disorders: Harmful and painful condition caused by overuse or overexertion of some part of the musculoskeletal system, often resulting from work-related physical activities. It is characterized by inflammation, pain, or dysfunction of the involved joints, bones, ligaments, and nerves. [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
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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] Cyclic: Pertaining to or occurring in a cycle or cycles; the term is applied to chemical compounds that contain a ring of atoms in the nucleus. [EU] Cyclin: Molecule that regulates the cell cycle. [NIH] Cyclophosphamide: Precursor of an alkylating nitrogen mustard antineoplastic and immunosuppressive agent that must be activated in the liver to form the active aldophosphamide. It is used in the treatment of lymphomas, leukemias, etc. Its side effect, alopecia, has been made use of in defleecing sheep. Cyclophosphamide may also cause sterility, birth defects, mutations, and cancer. [NIH] Cysteine: A thiol-containing non-essential amino acid that is oxidized to form cystine. [NIH] Cystine: A covalently linked dimeric nonessential amino acid formed by the oxidation of cysteine. Two molecules of cysteine are joined together by a disulfide bridge to form cystine. [NIH]
Cystitis: Inflammation of the urinary bladder. [EU] 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] 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] Cytoprotection: The process by which chemical compounds provide protection to cells against harmful agents. [NIH] Cytosine: A pyrimidine base that is a fundamental unit of nucleic acids. [NIH] Cytoskeletal Proteins: Major constituent of the cytoskeleton found in the cytoplasm of eukaryotic cells. They form a flexible framework for the cell, provide attachment points for organelles and formed bodies, and make communication between parts of the cell possible. [NIH]
Cytoskeleton: The network of filaments, tubules, and interconnecting filamentous bridges which give shape, structure, and organization to the cytoplasm. [NIH] Cytotoxic: Cell-killing. [NIH] Cytotoxicity: Quality of being capable of producing a specific toxic action upon cells of special organs. [NIH]
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Dairy Products: Raw and processed or manufactured milk and milk-derived products. These are usually from cows (bovine) but are also from goats, sheep, reindeer, and water buffalo. [NIH] Databases, Bibliographic: Extensive collections, reputedly complete, of references and citations to books, articles, publications, etc., generally on a single subject or specialized subject area. Databases can operate through automated files, libraries, or computer disks. The concept should be differentiated from factual databases which is used for collections of data and facts apart from bibliographic references to them. [NIH] Daunorubicin: Very toxic anthracycline aminoglycoside antibiotic isolated from Streptomyces peucetius and others, used in treatment of leukemias and other neoplasms. [NIH]
De novo: In cancer, the first occurrence of cancer in the body. [NIH] Deamination: The removal of an amino group (NH2) from a chemical compound. [NIH] Decarboxylation: The removal of a carboxyl group, usually in the form of carbon dioxide, from a chemical compound. [NIH] Decidua: The epithelial lining of the endometrium that is formed before the fertilized ovum reaches the uterus. The fertilized ovum embeds in the decidua. If the ovum is not fertilized, the decidua is shed during menstruation. [NIH] Decision Making: The process of making a selective intellectual judgment when presented with several complex alternatives consisting of several variables, and usually defining a course of action or an idea. [NIH] Defense Mechanisms: Unconscious process used by an individual or a group of individuals in order to cope with impulses, feelings or ideas which are not acceptable at their conscious level; various types include reaction formation, projection and self reversal. [NIH] Degenerative: Undergoing degeneration : tending to degenerate; having the character of or involving degeneration; causing or tending to cause degeneration. [EU] Dehydration: The condition that results from excessive loss of body water. [NIH] Dehydroepiandrosterone: DHEA. A substance that is being studied as a cancer prevention drug. It belongs to the family of drugs called steroids. [NIH] Deletion: A genetic rearrangement through loss of segments of DNA (chromosomes), bringing sequences, which are normally separated, into close proximity. [NIH] Dementia: An acquired organic mental disorder with loss of intellectual abilities of sufficient severity to interfere with social or occupational functioning. The dysfunction is multifaceted and involves memory, behavior, personality, judgment, attention, spatial relations, language, abstract thought, and other executive functions. The intellectual decline is usually progressive, and initially spares the level of consciousness. [NIH] Denaturation: Rupture of the hydrogen bonds by heating a DNA solution and then cooling it rapidly causes the two complementary strands to separate. [NIH] Dendrites: Extensions of the nerve cell body. They are short and branched and receive stimuli from other neurons. [NIH] Dendritic: 1. Branched like a tree. 2. Pertaining to or possessing dendrites. [EU] Dendritic cell: A special type of antigen-presenting cell (APC) that activates T lymphocytes. [NIH]
Density: The logarithm to the base 10 of the opacity of an exposed and processed film. [NIH] Deoxyguanosine: A nucleoside consisting of the base guanine and the sugar deoxyribose. [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] Deprivation: Loss or absence of parts, organs, powers, or things that are needed. [EU] Depsipeptide: Anticancer drugs obtained from microorganisms. [NIH] Dermal: Pertaining to or coming from the skin. [NIH] Dermatitis: Any inflammation of the skin. [NIH] DES: Diethylstilbestrol. A synthetic hormone that was prescribed from the early 1940s until 1971 to help women with complications of pregnancy. DES has been linked to an increased risk of clear cell carcinoma of the vagina in daughters of women who used DES. DES may also increase the risk of breast cancer in women who used DES. [NIH] 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] 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] Dextroamphetamine: The d-form of amphetamine. It is a central nervous system stimulant and a sympathomimetic. It has also been used in the treatment of narcolepsy and of attention deficit disorders and hyperactivity in children. Dextroamphetamine has multiple mechanisms of action including blocking uptake of adrenergics and dopamine, stimulating release of monamines, and inhibiting monoamine oxidase. It is also a drug of abuse and a psychotomimetic. [NIH] Diabetes Mellitus: A heterogeneous group of disorders that share glucose intolerance in common. [NIH] Diabetic Retinopathy: Retinopathy associated with diabetes mellitus, which may be of the background type, progressively characterized by microaneurysms, interretinal punctuate macular edema, or of the proliferative type, characterized by neovascularization of the retina and optic disk, which may project into the vitreous, proliferation of fibrous tissue, vitreous hemorrhage, and retinal detachment. [NIH] Diagnostic procedure: A method used to identify a disease. [NIH] Dialyzer: A part of the hemodialysis machine. (See hemodialysis under dialysis.) The dialyzer has two sections separated by a membrane. One section holds dialysate. The other holds the patient's blood. [NIH] Diastole: Period of relaxation of the heart, especially the ventricles. [NIH] Diastolic: Of or pertaining to the diastole. [EU] Diencephalon: The paired caudal parts of the prosencephalon from which the thalamus, hypothalamus, epithalamus, and subthalamus are derived. [NIH] Dietary Fats: Fats present in food, especially in animal products such as meat, meat products, butter, ghee. They are present in lower amounts in nuts, seeds, and avocados. [NIH]
Diethylcarbamazine: An anthelmintic used primarily as the citrate in the treatment of filariasis, particularly infestations with Wucheria bancrofti or Loa loa. [NIH] 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
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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] Diffusion: The tendency of a gas or solute to pass from a point of higher pressure or concentration to a point of lower pressure or concentration and to distribute itself throughout the available space; a major mechanism of biological transport. [NIH] Digestion: The process of breakdown of food for metabolism and use by the body. [NIH] Digestive 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] Dilatation, Pathologic: The condition of an anatomical structure's being dilated beyond normal dimensions. [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] Dilator: A device used to stretch or enlarge an opening. [NIH] Dilution: A diluted or attenuated medicine; in homeopathy, the diffusion of a given quantity of a medicinal agent in ten or one hundred times the same quantity of water. [NIH] Dimethyldithiocarbamate: A chemical that acts as a dopamine beta-hydroxylase inhibitor. Its salts are agricultural fungicides. It is inferior to diethyldithiocarbamate as a chelating agent. [NIH] Dipeptides: Peptides composed of two amino acid units. [NIH] Diphtheria: A localized infection of mucous membranes or skin caused by toxigenic strains of Corynebacterium diphtheriae. It is characterized by the presence of a pseudomembrane at the site of infection. Diphtheria toxin, produced by C. diphtheriae, can cause myocarditis, polyneuritis, and other systemic toxic effects. [NIH] Diphtheria Toxin: A 60 kD single chain protein elaborated by Corynebacterium diphtheriae that causes the sign and symptoms of diphtheria; it can be broken into two unequal fragments, the smaller (A fragment) inhibits protein synthesis and is the lethal moiety that needs the larger (B fragment) for entry into cells. [NIH] Diploid: Having two sets of chromosomes. [NIH] Direct: 1. Straight; in a straight line. 2. Performed immediately and without the intervention of subsidiary means. [EU] Disease Progression: The worsening of a disease over time. This concept is most often used for chronic and incurable diseases where the stage of the disease is an important determinant of therapy and prognosis. [NIH] Disease Susceptibility: A constitution or condition of the body which makes the tissues react in special ways to certain extrinsic stimuli and thus tends to make the individual more than usually susceptible to certain diseases. [NIH] Disease-Free Survival: Period after successful treatment in which there is no appearance of the symptoms or effects of the disease. [NIH] Disinfectant: An agent that disinfects; applied particularly to agents used on inanimate objects. [EU] Disinfection: Rendering pathogens harmless through the use of heat, antiseptics, antibacterial agents, etc. [NIH] Dissociation: 1. The act of separating or state of being separated. 2. The separation of a
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molecule into two or more fragments (atoms, molecules, ions, or free radicals) produced by the absorption of light or thermal energy or by solvation. 3. In psychology, a defense mechanism in which a group of mental processes are segregated from the rest of a person's mental activity in order to avoid emotional distress, as in the dissociative disorders (q.v.), or in which an idea or object is segregated from its emotional significance; in the first sense it is roughly equivalent to splitting, in the second, to isolation. 4. A defect of mental integration in which one or more groups of mental processes become separated off from normal consciousness and, thus separated, function as a unitary whole. [EU] Distal: Remote; farther from any point of reference; opposed to proximal. In dentistry, used to designate a position on the dental arch farther from the median line of the jaw. [EU] Disulphides: A covalent bridge formed by the oxidation of two cysteine residues to a cystine residue. The-S-S-bond is very strong and its presence confers additional stability. [NIH]
Dithiothreitol: A reagent commonly used in biochemical studies as a protective agent to prevent the oxidation of SH (thiol) groups and for reducing disulphides to dithiols. [NIH] Diuretic: A drug that increases the production of urine. [NIH] Dizziness: An imprecise term which may refer to a sense of spatial disorientation, motion of the environment, or lightheadedness. [NIH] Dopamine: An endogenous catecholamine and prominent neurotransmitter in several systems of the brain. In the synthesis of catecholamines from tyrosine, it is the immediate precursor to norepinephrine and epinephrine. Dopamine is a major transmitter in the extrapyramidal system of the brain, and important in regulating movement. A family of dopaminergic receptor subtypes mediate its action. Dopamine is used pharmacologically for its direct (beta adrenergic agonist) and indirect (adrenergic releasing) sympathomimetic effects including its actions as an inotropic agent and as a renal vasodilator. [NIH] Dorsal: 1. Pertaining to the back or to any dorsum. 2. Denoting a position more toward the back surface than some other object of reference; same as posterior in human anatomy; superior in the anatomy of quadrupeds. [EU] Dosage Forms: Completed forms of the pharmaceutical preparation in which prescribed doses of medication are included. They are designed to resist action by gastric fluids, prevent vomiting and nausea, reduce or alleviate the undesirable taste and smells associated with oral administration, achieve a high concentration of drug at target site, or produce a delayed or long-acting drug effect. They include capsules, liniments, ointments, pharmaceutical solutions, powders, tablets, etc. [NIH] Dose-limiting: Describes side effects of a drug or other treatment that are serious enough to prevent an increase in dose or level of that treatment. [NIH] 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] Doxycycline: A synthetic tetracycline derivative with a range of antimicrobial activity and mode of action similar to that of tetracycline, but more effective against many species. Animal studies suggest that it may cause less tooth staining than other tetracyclines. [NIH] 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]
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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] Drug Toxicity: Manifestations of the adverse effects of drugs administered therapeutically or in the course of diagnostic techniques. It does not include accidental or intentional poisoning for which specific headings are available. [NIH] Duodenum: The first part of the small intestine. [NIH] Dyes: Chemical substances that are used to stain and color other materials. The coloring may or may not be permanent. Dyes can also be used as therapeutic agents and test reagents in medicine and scientific research. [NIH] Dyspareunia: Painful sexual intercourse. [NIH] Dysplasia: Cells that look abnormal under a microscope but are not cancer. [NIH] Dystrophy: Any disorder arising from defective or faulty nutrition, especially the muscular dystrophies. [EU] Echocardiography: Ultrasonic recording of the size, motion, and composition of the heart and surrounding tissues. The standard approach is transthoracic. [NIH] 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] Egg Yolk: Cytoplasm stored in an egg that contains nutritional reserves for the developing embryo. It is rich in polysaccharides, lipids, and proteins. [NIH] Ejaculation: The release of semen through the penis during orgasm. [NIH] Elasticity: Resistance and recovery from distortion of shape. [NIH] Elastin: The protein that gives flexibility to tissues. [NIH] Elective: Subject to the choice or decision of the patient or physician; applied to procedures that are advantageous to the patient but not urgent. [EU] Electrocoagulation: Electrosurgical procedures used to treat hemorrhage (e.g., bleeding ulcers) and to ablate tumors, mucosal lesions, and refractory arrhythmias. [NIH] Electrolysis: Destruction by passage of a galvanic electric current, as in disintegration of a chemical compound in solution. [NIH] Electrolyte: A substance that dissociates into ions when fused or in solution, and thus becomes capable of conducting electricity; an ionic solute. [EU] Electrons: Stable elementary particles having the smallest known negative charge, present in all elements; also called negatrons. Positively charged electrons are called positrons. The numbers, energies and arrangement of electrons around atomic nuclei determine the
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chemical identities of elements. Beams of electrons are called cathode rays or beta rays, the latter being a high-energy biproduct of nuclear decay. [NIH] Electrophoresis: An electrochemical process in which macromolecules or colloidal particles with a net electric charge migrate in a solution under the influence of an electric current. [NIH]
Electrophysiological: Pertaining to electrophysiology, that is a branch of physiology that is concerned with the electric phenomena associated with living bodies and involved in their functional activity. [EU] Electroplating: Coating with a metal or alloy by electrolysis. [NIH] Elementary Particles: Individual components of atoms, usually subatomic; subnuclear particles are usually detected only when the atomic nucleus decays and then only transiently, as most of them are unstable, often yielding pure energy without substance, i.e., radiation. [NIH] ELISA: A sensitive analytical technique in which an enzyme is complexed to an antigen or antibody. A substrate is then added which generates a color proportional to the amount of binding. This method can be adapted to a solid-phase technique. [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] Embolization: The blocking of an artery by a clot or foreign material. Embolization can be done as treatment to block the flow of blood to a tumor. [NIH] Embolus: Bit of foreign matter which enters the blood stream at one point and is carried until it is lodged or impacted in an artery and obstructs it. It may be a blood clot, an air bubble, fat or other tissue, or clumps of bacteria. [NIH] Embryo: The prenatal stage of mammalian development characterized by rapid morphological changes and the differentiation of basic structures. [NIH] 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] Enalapril: An angiotensin-converting enzyme inhibitor that is used to treat hypertension. [NIH]
Encapsulated: Confined to a specific, localized area and surrounded by a thin layer of tissue. [NIH]
Encephalopathy: A disorder of the brain that can be caused by disease, injury, drugs, or chemicals. [NIH] Endarterectomy: Surgical excision, performed under general anesthesia, of the atheromatous tunica intima of an artery. When reconstruction of an artery is performed as an endovascular procedure through a catheter, it is called atherectomy. [NIH] Endemic: Present or usually prevalent in a population or geographical area at all times; said of a disease or agent. Called also endemial. [EU] Endocarditis: Exudative and proliferative inflammatory alterations of the endocardium,
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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] Endometrial: Having to do with the endometrium (the layer of tissue that lines the uterus). [NIH]
Endometriosis: A condition in which tissue more or less perfectly resembling the uterine mucous membrane (the endometrium) and containing typical endometrial granular and stromal elements occurs aberrantly in various locations in the pelvic cavity. [NIH] Endometrium: The layer of tissue that lines the uterus. [NIH] Endothelial cell: The main type of cell found in the inside lining of blood vessels, lymph vessels, and the heart. [NIH] Endothelium: A layer of epithelium that lines the heart, blood vessels (endothelium, vascular), lymph vessels (endothelium, lymphatic), and the serous cavities of the body. [NIH] Endothelium, Lymphatic: Unbroken cellular lining (intima) of the lymph vessels (e.g., the high endothelial lymphatic venules). It is more permeable than vascular endothelium, lacking selective absorption and functioning mainly to remove plasma proteins that have filtered through the capillaries into the tissue spaces. [NIH] Endothelium, Vascular: Single pavement layer of cells which line the luminal surface of the entire vascular system and regulate the transport of macromolecules and blood components from interstitium to lumen; this function has been most intensively studied in the blood capillaries. [NIH] Endothelium-derived: Small molecule that diffuses to the adjacent muscle layer and relaxes it. [NIH] Endotoxic: Of, relating to, or acting as an endotoxin (= a heat-stable toxin, associated with the outer membranes of certain gram-negative bacteria. Endotoxins are not secreted and are released only when the cells are disrupted). [EU] Endotoxin: Toxin from cell walls of bacteria. [NIH] End-stage renal: Total chronic kidney failure. When the kidneys fail, the body retains fluid and harmful wastes build up. A person with ESRD needs treatment to replace the work of the failed kidneys. [NIH] Enhancer: Transcriptional element in the virus genome. [NIH] Enkephalins: One of the three major families of endogenous opioid peptides. The enkephalins are pentapeptides that are widespread in the central and peripheral nervous systems and in the adrenal medulla. [NIH] Enterochromaffin Cells: Group of basal granular cells of the gut whose granules stain readily with silver and chromium salts. The cells secrete serotonin, substance P, and enkephalins. There are three types: gastric (antral mucosa), duodenal, and intestinal. [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]
Environmental Pollutants: Substances which pollute the environment. Use environmental pollutants in general or for which there is no specific heading. [NIH]
for
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Environmental tobacco smoke: ETS. Smoke that comes from the burning of a tobacco product and smoke that is exhaled by smokers (second-hand smoke). Inhaling ETS is called involuntary or passive smoking. [NIH] Enzymatic: Phase where enzyme cuts the precursor protein. [NIH] Enzyme: A protein that speeds up chemical reactions in the body. [NIH] Enzyme Induction: An increase in the rate of synthesis of an enzyme due to the presence of an inducer which acts to derepress the gene responsible for enzyme synthesis. [NIH] Enzyme Inhibitors: Compounds or agents that combine with an enzyme in such a manner as to prevent the normal substrate-enzyme combination and the catalytic reaction. [NIH] Enzyme-Linked Immunosorbent Assay: An immunoassay utilizing an antibody labeled with an enzyme marker such as horseradish peroxidase. While either the enzyme or the antibody is bound to an immunosorbent substrate, they both retain their biologic activity; the change in enzyme activity as a result of the enzyme-antibody-antigen reaction is proportional to the concentration of the antigen and can be measured spectrophotometrically or with the naked eye. Many variations of the method have been developed. [NIH] Epidemic: Occurring suddenly in numbers clearly in excess of normal expectancy; said especially of infectious diseases but applied also to any disease, injury, or other healthrelated event occurring in such outbreaks. [EU] Epidemiologic Studies: Studies designed to examine associations, commonly, hypothesized causal relations. They are usually concerned with identifying or measuring the effects of risk factors or exposures. The common types of analytic study are case-control studies, cohort studies, and cross-sectional studies. [NIH] Epidemiological: Relating to, or involving epidemiology. [EU] Epidermal: Pertaining to or resembling epidermis. Called also epidermic or epidermoid. [EU] Epidermal Growth Factor: A 6 kD polypeptide growth factor initially discovered in mouse submaxillary glands. Human epidermal growth factor was originally isolated from urine based on its ability to inhibit gastric secretion and called urogastrone. epidermal growth factor exerts a wide variety of biological effects including the promotion of proliferation and differentiation of mesenchymal and epithelial cells. [NIH] Epidermis: Nonvascular layer of the skin. It is made up, from within outward, of five layers: 1) basal layer (stratum basale epidermidis); 2) spinous layer (stratum spinosum epidermidis); 3) granular layer (stratum granulosum epidermidis); 4) clear layer (stratum lucidum epidermidis); and 5) horny layer (stratum corneum epidermidis). [NIH] Epidermoid carcinoma: A type of cancer in which the cells are flat and look like fish scales. Also called squamous cell carcinoma. [NIH] 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 cardiotoxicity. [NIH]
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Epithelial: Refers to the cells that line the internal and external surfaces of the body. [NIH] Epithelial Cells: Cells that line the inner and outer surfaces of the body. [NIH] Epithelium: One or more layers of epithelial cells, supported by the basal lamina, which covers the inner or outer surfaces of the body. [NIH] Epitope: A molecule or portion of a molecule capable of binding to the combining site of an antibody. For every given antigenic determinant, the body can construct a variety of antibody-combining sites, some of which fit almost perfectly, and others which barely fit. [NIH]
Erectile: The inability to get or maintain an erection for satisfactory sexual intercourse. Also called impotence. [NIH] Erection: The condition of being made rigid and elevated; as erectile tissue when filled with blood. [EU] Erythema: Redness of the skin produced by congestion of the capillaries. This condition may result from a variety of causes. [NIH] Erythrocytes: Red blood cells. Mature erythrocytes are non-nucleated, biconcave disks containing hemoglobin whose function is to transport oxygen. [NIH] Erythromycin: A bacteriostatic antibiotic substance produced by Streptomyces erythreus. Erythromycin A is considered its major active component. In sensitive organisms, it inhibits protein synthesis by binding to 50S ribosomal subunits. This binding process inhibits peptidyl transferase activity and interferes with translocation of amino acids during translation and assembly of proteins. [NIH] 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] Esophageal Spasms: Muscle cramps in the esophagus that cause pain in the chest. [NIH] Esophagus: The muscular tube through which food passes from the throat to the stomach. [NIH]
Essential Tremor: A rhythmic, involuntary, purposeless, oscillating movement resulting from the alternate contraction and relaxation of opposing groups of muscles. [NIH] Estrogen: One of the two female sex hormones. [NIH] Ethanol: A clear, colorless liquid rapidly absorbed from the gastrointestinal tract and distributed throughout the body. It has bactericidal activity and is used often as a topical disinfectant. It is widely used as a solvent and preservative in pharmaceutical preparations as well as serving as the primary ingredient in alcoholic beverages. [NIH] Ethanolamine: A viscous, hygroscopic amino alcohol with an ammoniacal odor. It is widely distributed in biological tissue and is a component of lecithin. It is used as a surfactant, fluorimetric reagent, and to remove CO2 and H2S from natural gas and other gases. [NIH] Ethoxyquin: Antioxidant; also a post-harvest dip to prevent scald on apples and pears. [NIH] Ethylene Dibromide: An effective soil fumigant, insecticide, and nematocide. In humans, it causes severe burning of skin and irritation of the eyes and respiratory tract. Prolonged inhalation may cause liver necrosis. It is also used in gasoline. Members of this group have caused liver and lung cancers in rodents. According to the Fourth Annual Report on Carcinogens (NTP 85-002, 1985), 1,2-dibromoethane may reasonably be anticipated to be a carcinogen. [NIH]
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Eukaryotic Cells: Cells of the higher organisms, containing a true nucleus bounded by a nuclear membrane. [NIH] Evoke: The electric response recorded from the cerebral cortex after stimulation of a peripheral sense organ. [NIH] Excitation: An act of irritation or stimulation or of responding to a stimulus; the addition of energy, as the excitation of a molecule by absorption of photons. [EU] Excitatory: When cortical neurons are excited, their output increases and each new input they receive while they are still excited raises their output markedly. [NIH] Excitotoxicity: Excessive exposure to glutamate or related compounds can kill brain neurons, presumably by overstimulating them. [NIH] Exfoliation: A falling off in scales or layers. [EU] Exhaustion: The feeling of weariness of mind and body. [NIH] Exogenous: Developed or originating outside the organism, as exogenous disease. [EU] Exons: Coding regions of messenger RNA included in the genetic transcript which survive the processing of RNA in cell nuclei to become part of a spliced messenger of structural RNA in the cytoplasm. They include joining and diversity exons of immunoglobulin genes. [NIH]
Expiration: The act of breathing out, or expelling air from the lungs. [EU] External-beam radiation: Radiation therapy that uses a machine to aim high-energy rays at the cancer. Also called external radiation. [NIH] Extracellular: Outside a cell or cells. [EU] Extracellular Matrix: A meshwork-like substance found within the extracellular space and in association with the basement membrane of the cell surface. It promotes cellular proliferation and provides a supporting structure to which cells or cell lysates in culture dishes adhere. [NIH] 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] Extracorporeal Circulation: Diversion of blood flow through a circuit located outside the body but continuous with the bodily circulation. [NIH] Extraction: The process or act of pulling or drawing out. [EU] Extrapyramidal: Outside of the pyramidal tracts. [EU] Eye Infections: Infection, moderate to severe, caused by bacteria, fungi, or viruses, which occurs either on the external surface of the eye or intraocularly with probable inflammation, visual impairment, or blindness. [NIH] Facial: Of or pertaining to the face. [EU] Fallopian Tubes: Two long muscular tubes that transport ova from the ovaries to the uterus.
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They extend from the horn of the uterus to the ovaries and consist of an ampulla, an infundibulum, an isthmus, two ostia, and a pars uterina. The walls of the tubes are composed of three layers: mucosal, muscular, and serosal. [NIH] Family Planning: Programs or services designed to assist the family in controlling reproduction by either improving or diminishing fertility. [NIH] Fat: Total lipids including phospholipids. [NIH] Fatal Outcome: Death resulting from the presence of a disease in an individual, as shown by a single case report or a limited number of patients. This should be differentiated from death, the physiological cessation of life and from mortality, an epidemiological or statistical concept. [NIH] Fatigue: The state of weariness following a period of exertion, mental or physical, characterized by a decreased capacity for work and reduced efficiency to respond to stimuli. [NIH]
Fatty acids: A major component of fats that are used by the body for energy and tissue development. [NIH] Fermentation: An enzyme-induced chemical change in organic compounds that takes place in the absence of oxygen. The change usually results in the production of ethanol or lactic acid, and the production of energy. [NIH] Ferritin: An iron-containing protein complex that is formed by a combination of ferric iron with the protein apoferritin. [NIH] Fertilizers: Substances or mixtures that are added to the soil to supply nutrients or to make available nutrients already present in the soil, in order to increase plant growth and productivity. [NIH] Fetus: The developing offspring from 7 to 8 weeks after conception until birth. [NIH] Fibrin: A protein derived from fibrinogen in the presence of thrombin, which forms part of the blood clot. [NIH] Fibroblast Growth Factor: Peptide isolated from the pituitary gland and from the brain. It is a potent mitogen which stimulates growth of a variety of mesodermal cells including chondrocytes, granulosa, and endothelial cells. The peptide may be active in wound healing and animal limb regeneration. [NIH] Fibroblasts: Connective tissue cells which secrete an extracellular matrix rich in collagen and other macromolecules. [NIH] Fibrosis: Any pathological condition where fibrous connective tissue invades any organ, usually as a consequence of inflammation or other injury. [NIH] Fixation: 1. The act or operation of holding, suturing, or fastening in a fixed position. 2. The condition of being held in a fixed position. 3. In psychiatry, a term with two related but distinct meanings : (1) arrest of development at a particular stage, which like regression (return to an earlier stage), if temporary is a normal reaction to setbacks and difficulties but if protracted or frequent is a cause of developmental failures and emotional problems, and (2) a close and suffocating attachment to another person, especially a childhood figure, such as one's mother or father. Both meanings are derived from psychoanalytic theory and refer to 'fixation' of libidinal energy either in a specific erogenous zone, hence fixation at the oral, anal, or phallic stage, or in a specific object, hence mother or father fixation. 4. The use of a fixative (q.v.) to preserve histological or cytological specimens. 5. In chemistry, the process whereby a substance is removed from the gaseous or solution phase and localized, as in carbon dioxide fixation or nitrogen fixation. 6. In ophthalmology, direction of the gaze so that the visual image of the object falls on the fovea centralis. 7. In film processing, the
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chemical removal of all undeveloped salts of the film emulsion, leaving only the developed silver to form a permanent image. [EU] 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 sorting. Other measurable optical parameters include light absorption and light scattering, the latter being applicable to the measurement of cell size, shape, density, granularity, and stain uptake. [NIH] Fluorescence: The property of emitting radiation while being irradiated. The radiation emitted is usually of longer wavelength than that incident or absorbed, e.g., a substance can be irradiated with invisible radiation and emit visible light. X-ray fluorescence is used in diagnosis. [NIH] Fluorescent Dyes: Dyes that emit light when exposed to light. The wave length of the emitted light is usually longer than that of the incident light. Fluorochromes are substances that cause fluorescence in other substances, i.e., dyes used to mark or label other compounds with fluorescent tags. They are used as markers in biochemistry and immunology. [NIH] Foetoplacental: Pertaining to the fetus and placenta. [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] Forearm: The part between the elbow and the wrist. [NIH] Forskolin: Potent activator of the adenylate cyclase system and the biosynthesis of cyclic AMP. From the plant Coleus forskohlii. Has antihypertensive, positive ionotropic, platelet aggregation inhibitory, and smooth muscle relaxant activities; also lowers intraocular pressure and promotes release of hormones from the pituitary gland. [NIH] Fovea: The central part of the macula that provides the sharpest vision. [NIH] Fractionation: Dividing the total dose of radiation therapy into several smaller, equal doses delivered over a period of several days. [NIH] Frameshift: A type of mutation which causes out-of-phase transcription of the base sequence; such mutations arise from the addition or delection of nucleotide(s) in numbers other than 3 or multiples of 3. [NIH] Frameshift Mutation: A type of mutation in which a number of nucleotides not divisible by three is deleted from or inserted into a coding sequence, thereby causing an alteration in the reading frame of the entire sequence downstream of the mutation. These mutations may be induced by certain types of mutagens or may occur spontaneously. [NIH] Friction: Surface resistance to the relative motion of one body against the rubbing, sliding, rolling, or flowing of another with which it is in contact. [NIH]
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Fructans: Polysaccharides composed of D-fructose units. [NIH] Fructose: A type of sugar found in many fruits and vegetables and in honey. Fructose is used to sweeten some diet foods. It is considered a nutritive sweetener because it has calories. [NIH] Fulminant Hepatic Failure: Liver failure that occurs suddenly in a previously healthy person. The most common causes of FHF are acute hepatitis, acetaminophen overdose, and liver damage from prescription drugs. [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] Fungicide: An agent that destroys fungi. [EU] Fungistatic: Inhibiting the growth of fungi. [EU] Gallate: Antioxidant present in tea. [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] Gamma-Glutamyltransferase: An enzyme that catalyzes reversibly the transfer of a glutamyl group from a glutamyl-peptide and an amino acid to a peptide and a glutamylamino acid. EC 2.3.2.2. [NIH] Gamma-interferon: Interferon produced by T-lymphocytes in response to various mitogens and antigens. Gamma interferon appears to have potent antineoplastic, immunoregulatory and antiviral activity. [NIH] Ganglia: Clusters of multipolar neurons surrounded by a capsule of loosely organized connective tissue located outside the central nervous system. [NIH] Gap Junctions: Connections between cells which allow passage of small molecules and electric current. Gap junctions were first described anatomically as regions of close apposition between cells with a narrow (1-2 nm) gap between cell membranes. The variety in the properties of gap junctions is reflected in the number of connexins, the family of proteins which form the junctions. [NIH] Gas: Air that comes from normal breakdown of food. The gases are passed out of the body through the rectum (flatus) or the mouth (burp). [NIH] Gas exchange: Primary function of the lungs; transfer of oxygen from inhaled air into the blood and of carbon dioxide from the blood into the lungs. [NIH] Gasoline: Volative flammable fuel (liquid hydrocarbons) derived from crude petroleum by processes such as distillation reforming, polymerization, etc. [NIH] Gastric: Having to do with the stomach. [NIH] Gastrin: A hormone released after eating. Gastrin causes the stomach to produce more acid. [NIH]
Gastritis: Inflammation of the stomach. [EU] Gastroenteritis: An acute inflammation of the lining of the stomach and intestines, characterized by anorexia, nausea, diarrhoea, abdominal pain, and weakness, which has various causes, including food poisoning due to infection with such organisms as Escherichia coli, Staphylococcus aureus, and Salmonella species; consumption of irritating food or drink; or psychological factors such as anger, stress, and fear. Called also enterogastritis. [EU]
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Gastrointestinal: Refers to the stomach and intestines. [NIH] Gastrointestinal tract: The stomach and intestines. [NIH] Gelatin: A product formed from skin, white connective tissue, or bone collagen. It is used as a protein food adjuvant, plasma substitute, hemostatic, suspending agent in pharmaceutical preparations, and in the manufacturing of capsules and suppositories. [NIH] Gene: The functional and physical unit of heredity passed from parent to offspring. Genes are pieces of DNA, and most genes contain the information for making a specific protein. [NIH]
Gene Expression: The phenotypic manifestation of a gene or genes by the processes of gene action. [NIH] Gene Silencing: Interruption or suppression of the expression of a gene at transcriptional or translational levels. [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] Generator: Any system incorporating a fixed parent radionuclide from which is produced a daughter radionuclide which is to be removed by elution or by any other method and used in a radiopharmaceutical. [NIH] Genetic Code: The specifications for how information, stored in nucleic acid sequence (base sequence), is translated into protein sequence (amino acid sequence). The start, stop, and order of amino acids of a protein is specified by consecutive triplets of nucleotides called codons (codon). [NIH] Genetic Engineering: Directed modification of the gene complement of a living organism by such techniques as altering the DNA, substituting genetic material by means of a virus, transplanting whole nuclei, transplanting cell hybrids, etc. [NIH] Genetic Markers: A phenotypically recognizable genetic trait which can be used to identify a genetic locus, a linkage group, or a recombination event. [NIH] Genetics: The biological science that deals with the phenomena and mechanisms of heredity. [NIH] Genital: Pertaining to the genitalia. [EU] Genitourinary: Pertaining to the genital and urinary organs; urogenital; urinosexual. [EU] Genitourinary system: The parts of the body that play a role in reproduction, getting rid of waste products in the form of urine, or both. [NIH] Genotype: The genetic constitution of the individual; the characterization of the genes. [NIH] Geriatric: Pertaining to the treatment of the aged. [EU] Germ Cells: The reproductive cells in multicellular organisms. [NIH] Germline mutation: A gene change in the body's reproductive cells (egg or sperm) that becomes incorporated into the DNA of every cell in the body of offspring; germline mutations are passed on from parents to offspring. Also called hereditary mutation. [NIH] Gestation: The period of development of the young in viviparous animals, from the time of fertilization of the ovum until birth. [EU] Giant Cells: Multinucleated masses produced by the fusion of many cells; often associated with viral infections. In AIDS, they are induced when the envelope glycoprotein of the HIV virus binds to the CD4 antigen of uninfected neighboring T4 cells. The resulting syncytium leads to cell death and thus may account for the cytopathic effect of the virus. [NIH]
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Ginger: Deciduous plant rich in volatile oil (oils, volatile). It is used as a flavoring agent and has many other uses both internally and topically. [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] Glioblastoma: A malignant form of astrocytoma histologically characterized by pleomorphism of cells, nuclear atypia, microhemorrhage, and necrosis. They may arise in any region of the central nervous system, with a predilection for the cerebral hemispheres, basal ganglia, and commissural pathways. Clinical presentation most frequently occurs in the fifth or sixth decade of life with focal neurologic signs or seizures. [NIH] Glioma: A cancer of the brain that comes from glial, or supportive, cells. [NIH] Glottis: The vocal apparatus of the larynx, consisting of the true vocal cords (plica vocalis) and the opening between them (rima glottidis). [NIH] Glucocorticoid: A compound that belongs to the family of compounds called corticosteroids (steroids). Glucocorticoids affect metabolism and have anti-inflammatory and immunosuppressive effects. They may be naturally produced (hormones) or synthetic (drugs). [NIH] Glucose: D-Glucose. A primary source of energy for living organisms. It is naturally occurring and is found in fruits and other parts of plants in its free state. It is used therapeutically in fluid and nutrient replacement. [NIH] Glucose Intolerance: A pathological state in which the fasting plasma glucose level is less than 140 mg per deciliter and the 30-, 60-, or 90-minute plasma glucose concentration following a glucose tolerance test exceeds 200 mg per deciliter. This condition is seen frequently in diabetes mellitus but also occurs with other diseases. [NIH] Glucosinolates: Substituted thioglucosides. They are found in rapeseed (Brassica campestris) products and related Cruciferae. They are metabolized to a variety of toxic products which are most likely the cause of hepatocytic necrosis in animals and humans. [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] Glucuronides: Glycosides of glucuronic acid formed by the reaction of uridine diphosphate glucuronic acid with certain endogenous and exogenous substances. Their formation is important for the detoxification of drugs, steroid excretion and bilirubin metabolism to a more water-soluble compound that can be eliminated in the urine and bile. [NIH] Glucuronosyltransferase: A family of enzymes accepting a wide range of substrates, including phenols, alcohols, amines, and fatty acids. They function as drug-metabolizing enzymes that catalyze the conjugation of UDPglucuronic acid to a variety of endogenous and exogenous compounds. EC 2.4.1.17. [NIH] Glutamate: Excitatory neurotransmitter of the brain. [NIH] Glutamate-Cysteine Ligase: One of the enzymes active in the gamma-glutamyl cycle. It catalyzes the synthesis of gamma-glutamylcysteine from glutamate and cysteine in the presence of ATP with the formation of ADP and orthophosphate. EC 6.3.2.2. [NIH] Glutamic Acid: A non-essential amino acid naturally occurring in the L-form. Glutamic acid
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(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]
Glutathione Transferase: A transferase that catalyzes the addition of aliphatic, aromatic, or heterocyclic radicals as well as epoxides and arene oxides to glutathione. Addition takes place at the sulfur atom. It also catalyzes the reduction of polyol nitrate by glutathione to polyol and nitrite. EC 2.5.1.18. [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] Glycols: A generic grouping for dihydric alcohols with the hydroxy groups (-OH) located on different carbon atoms. They are viscous liquids with high boiling points for their molecular weights. [NIH] Glycoprotein: A protein that has sugar molecules attached to it. [NIH] 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] Glycosidic: Formed by elimination of water between the anomeric hydroxyl of one sugar and a hydroxyl of another sugar molecule. [NIH] Goats: Any of numerous agile, hollow-horned ruminants of the genus Capra, closely related to the sheep. [NIH] Gonadal: Pertaining to a gonad. [EU] Gonorrhoea: Infection due to Neisseria gonorrhoeae transmitted sexually in most cases, but also by contact with infected exudates in neonatal children at birth, or by infants in households with infected inhabitants. It is marked in males by urethritis with pain and purulent discharge, but is commonly asymptomatic in females, although it may extend to produce suppurative salpingitis, oophoritis, tubo-ovarian abscess, and peritonitis. Bacteraemia occurs in both sexes, resulting in cutaneous lesions, arthritis, and rarely meningitis or endocarditis. Formerly called blennorrhagia and blennorrhoea. [EU] Gout: Hereditary metabolic disorder characterized by recurrent acute arthritis, hyperuricemia and deposition of sodium urate in and around the joints, sometimes with formation of uric acid calculi. [NIH] Governing Board: The group in which legal authority is vested for the control of healthrelated institutions and organizations. [NIH] Gp120: 120-kD HIV envelope glycoprotein which is involved in the binding of the virus to
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its membrane receptor, the CD4 molecule, found on the surface of certain cells in the body. [NIH]
GP41: 41-kD HIV transmembrane envelope glycoprotein which mediates the fusion of the viral membrane with the membrane of the target cell. [NIH] Grade: The grade of a tumor depends on how abnormal the cancer cells look under a microscope and how quickly the tumor is likely to grow and spread. Grading systems are different for each type of cancer. [NIH] 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] Granule: A small pill made from sucrose. [EU] Granulocyte Colony-Stimulating Factor: A glycoprotein of MW 25 kDa containing internal disulfide bonds. It induces the survival, proliferation, and differentiation of neutrophilic granulocyte precursor cells and functionally activates mature blood neutrophils. Among the family of colony-stimulating factors, G-CSF is the most potent inducer of terminal differentiation to granulocytes and macrophages of leukemic myeloid cell lines. [NIH] Granulocytes: Leukocytes with abundant granules in the cytoplasm. They are divided into three groups: neutrophils, eosinophils, and basophils. [NIH] Grasses: A large family, Gramineae, of narrow-leaved herbaceous monocots. Many grasses produce highly allergenic pollens and are hosts to cattle parasites and toxic fungi. [NIH] Gravis: Eruption of watery blisters on the skin among those handling animals and animal products. [NIH] Growth: The progressive development of a living being or part of an organism from its earliest stage to maturity. [NIH] Growth factors: Substances made by the body that function to regulate cell division and cell survival. Some growth factors are also produced in the laboratory and used in biological therapy. [NIH] Guanylate Cyclase: An enzyme that catalyzes the conversion of GTP to 3',5'-cyclic GMP and pyrophosphate. It also acts on ITP and dGTP. (From Enzyme Nomenclature, 1992) EC 4.6.1.2. [NIH] 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] Haploid: An organism with one basic chromosome set, symbolized by n; the normal condition of gametes in diploids. [NIH] Haptens: Small antigenic determinants capable of eliciting an immune response only when coupled to a carrier. Haptens bind to antibodies but by themselves cannot elicit an antibody response. [NIH] Hazardous Waste: Waste products which, upon release into the atmosphere, water or soil, cause health risks to humans or animals through skin contact, inhalation or ingestion. Hazardous waste sites which contain hazardous waste substances go here. [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]
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Headache Disorders: Common conditions characterized by persistent or recurrent headaches. Headache syndrome classification systems may be based on etiology (e.g., vascular headache, post-traumatic headaches, etc.), temporal pattern (e.g., cluster headache, paroxysmal hemicrania, etc.), and precipitating factors (e.g., cough headache). [NIH] Health Policy: Decisions, usually developed by government policymakers, for determining present and future objectives pertaining to the health care system. [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] Heart Transplantation: The transference of a heart from one human or animal to another. [NIH]
Hematocrit: Measurement of the volume of packed red cells in a blood specimen by centrifugation. The procedure is performed using a tube with graduated markings or with automated blood cell counters. It is used as an indicator of erythrocyte status in disease. For example, anemia shows a low hematocrit, polycythemia, high values. [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] Hemodialysis: The use of a machine to clean wastes from the blood after the kidneys have failed. The blood travels through tubes to a dialyzer, which removes wastes and extra fluid. The cleaned blood then flows through another set of tubes back into the body. [NIH] Hemodynamics: The movements of the blood and the forces involved in systemic or regional blood circulation. [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] 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] Hepatitis A: Hepatitis caused by hepatovirus. It can be transmitted through fecal
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contamination of food or water. [NIH] Hepatocellular: Pertaining to or affecting liver cells. [EU] Hepatocellular carcinoma: A type of adenocarcinoma, the most common type of liver tumor. [NIH] Hepatocyte: A liver cell. [NIH] Hepatotoxic: Toxic to liver cells. [EU] Hepatotoxicity: How much damage a medicine or other substance does to the liver. [NIH] Hepatovirus: A genus of Picornaviridae causing infectious hepatitis naturally in humans and experimentally in other primates. It is transmitted through fecal contamination of food or water. [NIH] Herbicide: A chemical that kills plants. [NIH] Hereditary: Of, relating to, or denoting factors that can be transmitted genetically from one generation to another. [NIH] Hereditary mutation: A gene change in the body's reproductive cells (egg or sperm) that becomes incorporated into the DNA of every cell in the body of offspring; hereditary mutations are passed on from parents to offspring. Also called germline mutation. [NIH] Heredity: 1. The genetic transmission of a particular quality or trait from parent to offspring. 2. The genetic constitution of an individual. [EU] Herpes: Any inflammatory skin disease caused by a herpesvirus and characterized by the formation of clusters of small vesicles. When used alone, the term may refer to herpes simplex or to herpes zoster. [EU] Herpes virus: A member of the herpes family of viruses. [NIH] Herpes Zoster: Acute vesicular inflammation. [NIH] Heterodimer: Zippered pair of nonidentical proteins. [NIH] Heterogeneity: The property of one or more samples or populations which implies that they are not identical in respect of some or all of their parameters, e. g. heterogeneity of variance. [NIH]
Heterozygotes: Having unlike alleles at one or more corresponding loci on homologous chromosomes. [NIH] Hiccup: A spasm of the diaphragm that causes a sudden inhalation followed by rapid closure of the glottis which produces a sound. [NIH] Hippocampus: A curved elevation of gray matter extending the entire length of the floor of the temporal horn of the lateral ventricle (Dorland, 28th ed). The hippocampus, subiculum, and dentate gyrus constitute the hippocampal formation. Sometimes authors include the entorhinal cortex in the hippocampal formation. [NIH] Histamine: 1H-Imidazole-4-ethanamine. A depressor amine derived by enzymatic decarboxylation of histidine. It is a powerful stimulant of gastric secretion, a constrictor of bronchial smooth muscle, a vasodilator, and also a centrally acting neurotransmitter. [NIH] Histidine: An essential amino acid important in a number of metabolic processes. It is required for the production of histamine. [NIH] Histocompatibility: The degree of antigenic similarity between the tissues of different individuals, which determines the acceptance or rejection of allografts. [NIH] Histology: The study of tissues and cells under a microscope. [NIH] Histone Deacetylase: Hydrolyzes N-acetyl groups on histones. [NIH]
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Homeostasis: The processes whereby the internal environment of an organism tends to remain balanced and stable. [NIH] Homogeneous: Consisting of or composed of similar elements or ingredients; of a uniform quality throughout. [EU] Homologous: Corresponding in structure, position, origin, etc., as (a) the feathers of a bird and the scales of a fish, (b) antigen and its specific antibody, (c) allelic chromosomes. [EU] Homozygotes: An individual having a homozygous gene pair. [NIH] Hormonal: Pertaining to or of the nature of a hormone. [EU] Hormone: A substance in the body that regulates certain organs. Hormones such as gastrin help in breaking down food. Some hormones come from cells in the stomach and small intestine. [NIH] Horny layer: The superficial layer of the epidermis containing keratinized cells. [NIH] Horseradish Peroxidase: An enzyme isolated from horseradish which is able to act as an antigen. It is frequently used as a histochemical tracer for light and electron microscopy. Its antigenicity has permitted its use as a combined antigen and marker in experimental immunology. [NIH] Host: Any animal that receives a transplanted graft. [NIH] Housekeeping: The care and management of property. [NIH] Human growth hormone: A protein hormone, secreted by the anterior lobe of the pituitary, which promotes growth of the whole body by stimulating protein synthesis. The human gene has already been cloned and successfully expressed in bacteria. [NIH] Humoral: Of, relating to, proceeding from, or involving a bodily humour - now often used of endocrine factors as opposed to neural or somatic. [EU] Humour: 1. A normal functioning fluid or semifluid of the body (as the blood, lymph or bile) especially of vertebrates. 2. A secretion that is itself an excitant of activity (as certain hormones). [EU] Hybrid: Cross fertilization between two varieties or, more usually, two species of vines, see also crossing. [NIH] Hybridization: The genetic process of crossbreeding to produce a hybrid. Hybrid nucleic acids can be formed by nucleic acid hybridization of DNA and RNA molecules. Protein hybridization allows for hybrid proteins to be formed from polypeptide chains. [NIH] Hybridomas: Cells artificially created by fusion of activated lymphocytes with neoplastic cells. The resulting hybrid cells are cloned and produce pure or "monoclonal" antibodies or T-cell products, identical to those produced by the immunologically competent parent, and continually grow and divide as the neoplastic parent. [NIH] 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, 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
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unless stabilized by the addition of acetanilide or similar organic materials. [NIH] Hydrolysis: The process of cleaving a chemical compound by the addition of a molecule of water. [NIH] Hydrophobic: Not readily absorbing water, or being adversely affected by water, as a hydrophobic colloid. [EU] Hydroxides: Inorganic compounds that contain the OH- group. [NIH] Hydroxy Acids: Organic compounds containing both the hydroxyl and carboxyl radicals. [NIH]
Hydroxyl Radical: The univalent radical OH that is present in hydroxides, alcohols, phenols, glycols. [NIH] Hydroxylysine: A hydroxylated derivative of the amino acid lysine that is present in certain collagens. [NIH] Hydroxyproline: A hydroxylated form of the imino acid proline. A deficiency in ascorbic acid can result in impaired hydroxyproline formation. [NIH] Hyperbaric: Characterized by greater than normal pressure or weight; applied to gases under greater than atmospheric pressure, as hyperbaric oxygen, or to a solution of greater specific gravity than another taken as a standard of reference. [EU] Hyperbaric oxygen: Oxygen that is at an atmospheric pressure higher than the pressure at sea level. Breathing hyperbaric oxygen to enhance the effectiveness of radiation therapy is being studied. [NIH] Hyperbilirubinemia: Pathologic process consisting of an abnormal increase in the amount of bilirubin in the circulating blood, which may result in jaundice. [NIH] Hyperglycemia: Abnormally high blood sugar. [NIH] Hypersensitivity: Altered reactivity to an antigen, which can result in pathologic reactions upon subsequent exposure to that particular antigen. [NIH] Hypertension: Persistently high arterial blood pressure. Currently accepted threshold levels are 140 mm Hg systolic and 90 mm Hg diastolic pressure. [NIH] Hypokinesia: Slow or diminished movement of body musculature. It may be associated with basal ganglia diseases; mental disorders; prolonged inactivity due to illness; experimental protocols used to evaluate the physiologic effects of immobility; and other conditions. [NIH] Hypotension: Abnormally low blood pressure. [NIH] Hypothermia: Lower than normal body temperature, especially in warm-blooded animals; in man usually accidental or unintentional. [NIH] Hypoxanthine: A purine and a reaction intermediate in the metabolism of adenosine and in the formation of nucleic acids by the salvage pathway. [NIH] Hypoxia: Reduction of oxygen supply to tissue below physiological levels despite adequate perfusion of the tissue by blood. [EU] Id: The part of the personality structure which harbors the unconscious instinctive desires and strivings of the individual. [NIH] Idarubicin: An orally administered anthracycline antibiotic. The compound has shown activity against breast cancer, lymphomas and leukemias, together with potential for reduced cardiac toxicity. [NIH] Idiopathic: Describes a disease of unknown cause. [NIH] Ifosfamide: Positional isomer of cyclophosphamide which is active as an alkylating agent
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and an immunosuppressive agent. [NIH] Ileitis: Inflammation of the ileum. [EU] Ileum: The lower end of the small intestine. [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
of
foreign
Immunoassay: Immunochemical assay or detection of a substance by serologic or immunologic methods. Usually the substance being studied serves as antigen both in antibody production and in measurement of antibody by the test substance. [NIH] Immunoblotting: Immunologic methods for isolating and quantitatively measuring immunoreactive substances. When used with immune reagents such as monoclonal antibodies, the process is known generically as western blot analysis (blotting, western). [NIH]
Immunocompromised: Having a weakened immune system caused by certain diseases or treatments. [NIH] Immunodeficiency: The decreased ability of the body to fight infection and disease. [NIH] Immunogenic: Producing immunity; evoking an immune response. [EU] Immunoglobulin: A protein that acts as an antibody. [NIH] Immunologic: The ability of the antibody-forming system to recall a previous experience with an antigen and to respond to a second exposure with the prompt production of large amounts of antibody. [NIH] Immunology: The study of the body's immune system. [NIH] Immunomodulator: New type of drugs mainly using biotechnological methods. Treatment of cancer. [NIH] Immunosuppressant: An agent capable of suppressing immune responses. [EU] Immunosuppressive: Describes the ability to lower immune system responses. [NIH] Immunotoxins: Semisynthetic conjugates of various toxic molecules, including radioactive isotopes and bacterial or plant toxins, with specific immune substances such as immunoglobulins, monoclonal antibodies, and antigens. The antitumor or antiviral immune substance carries the toxin to the tumor or infected cell where the toxin exerts its poisonous effect. [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] Impotence: The inability to perform sexual intercourse. [NIH] In situ: In the natural or normal place; confined to the site of origin without invasion of neighbouring tissues. [EU]
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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] Incompetence: Physical or mental inadequacy or insufficiency. [EU] Incontinence: Inability to control the flow of urine from the bladder (urinary incontinence) or the escape of stool from the rectum (fecal incontinence). [NIH] Incubation: The development of an infectious disease from the entrance of the pathogen to the appearance of clinical symptoms. [EU] Incubation period: The period of time likely to elapse between exposure to the agent of the disease and the onset of clinical symptoms. [NIH] Indicative: That indicates; that points out more or less exactly; that reveals fairly clearly. [EU] Indolent: A type of cancer that grows slowly. [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] Infarction: A pathological process consisting of a sudden insufficient blood supply to an area, which results in necrosis of that area. It is usually caused by a thrombus, an embolus, or a vascular torsion. [NIH] Infection: 1. Invasion and multiplication of microorganisms in body tissues, which may be clinically unapparent or result in local cellular injury due to competitive metabolism, toxins, intracellular replication, or antigen-antibody response. The infection may remain localized, subclinical, and temporary if the body's defensive mechanisms are effective. A local infection may persist and spread by extension to become an acute, subacute, or chronic clinical infection or disease state. A local infection may also become systemic when the microorganisms gain access to the lymphatic or vascular system. 2. An infectious disease. [EU]
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] Inflammation: A pathological process characterized by injury or destruction of tissues caused by a variety of cytologic and chemical reactions. It is usually manifested by typical signs of pain, heat, redness, swelling, and loss of function. [NIH] Inflammatory bowel disease: A general term that refers to the inflammation of the colon and rectum. Inflammatory bowel disease includes ulcerative colitis and Crohn's disease. [NIH]
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
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then cemented into the cavity. [NIH] Inner ear: The labyrinth, comprising the vestibule, cochlea, and semicircular canals. [NIH] Inorganic: Pertaining to substances not of organic origin. [EU] Inotropic: Affecting the force or energy of muscular contractions. [EU] Insecticides: Pesticides designed to control insects that are harmful to man. The insects may be directly harmful, as those acting as disease vectors, or indirectly harmful, as destroyers of crops, food products, or textile fabrics. [NIH] Insight: The capacity to understand one's own motives, to be aware of one's own psychodynamics, to appreciate the meaning of symbolic behavior. [NIH] Insulator: Material covering the metal conductor of the lead. It is usually polyurethane or silicone. [NIH] Insulin: A protein hormone secreted by beta cells of the pancreas. Insulin plays a major role in the regulation of glucose metabolism, generally promoting the cellular utilization of glucose. It is also an important regulator of protein and lipid metabolism. Insulin is used as a drug to control insulin-dependent diabetes mellitus. [NIH] Insulin-dependent diabetes mellitus: A disease characterized by high levels of blood glucose resulting from defects in insulin secretion, insulin action, or both. Autoimmune, genetic, and environmental factors are involved in the development of type I diabetes. [NIH] Intensive Care: Advanced and highly specialized care provided to medical or surgical patients whose conditions are life-threatening and require comprehensive care and constant monitoring. It is usually administered in specially equipped units of a health care facility. [NIH]
Intensive Care Units: Hospital units providing continuous surveillance and care to acutely ill patients. [NIH] Intercellular Adhesion Molecule-1: A cell-surface ligand with a role in leukocyte adhesion and inflammation. Its production is induced by gamma-interferon and it is required for neutrophil migration into inflamed tissue. [NIH] Interferon: A biological response modifier (a substance that can improve the body's natural response to disease). Interferons interfere with the division of cancer cells and can slow tumor growth. There are several types of interferons, including interferon-alpha, -beta, and gamma. These substances are normally produced by the body. They are also made in the laboratory for use in treating cancer and other diseases. [NIH] Interferon-alpha: One of the type I interferons produced by peripheral blood leukocytes or lymphoblastoid cells when exposed to live or inactivated virus, double-stranded RNA, or bacterial products. It is the major interferon produced by virus-induced leukocyte cultures and, in addition to its pronounced antiviral activity, it causes activation of NK cells. [NIH] Interleukin-1: A soluble factor produced by monocytes, macrophages, and other cells which activates T-lymphocytes and potentiates their response to mitogens or antigens. IL-1 consists of two distinct forms, IL-1 alpha and IL-1 beta which perform the same functions but are distinct proteins. The biological effects of IL-1 include the ability to replace macrophage requirements for T-cell activation. The factor is distinct from interleukin-2. [NIH] Interleukin-2: Chemical mediator produced by activated T lymphocytes and which regulates the proliferation of T cells, as well as playing a role in the regulation of NK cell activity. [NIH] Interleukin-6: Factor that stimulates the growth and differentiation of human B-cells and is also a growth factor for hybridomas and plasmacytomas. It is produced by many different cells including T-cells, monocytes, and fibroblasts. [NIH]
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Intermediate Filaments: Cytoplasmic filaments intermediate in diameter (about 10 nanometers) between the microfilaments and the microtubules. They may be composed of any of a number of different proteins and form a ring around the cell nucleus. [NIH] 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] Intestinal: Having to do with the intestines. [NIH] Intestine: A long, tube-shaped organ in the abdomen that completes the process of digestion. There is both a large intestine and a small intestine. Also called the bowel. [NIH] Intoxication: Poisoning, the state of being poisoned. [EU] Intracellular: Inside a cell. [NIH] Intracranial Embolism: The sudden obstruction of a blood vessel by an embolus. [NIH] Intracranial Embolism and Thrombosis: Embolism or thrombosis involving blood vessels which supply intracranial structures. Emboli may originate from extracranial or intracranial sources. Thrombosis may occur in arterial or venous structures. [NIH] Intramuscular: IM. Within or into muscle. [NIH] Intraocular: Within the eye. [EU] Intraocular pressure: Pressure of the fluid inside the eye; normal IOP varies among individuals. [NIH] Intravenous: IV. Into a vein. [NIH] Intrinsic: Situated entirely within or pertaining exclusively to a part. [EU] Introns: Non-coding, intervening sequences of DNA that are transcribed, but are removed from within the primary gene transcript and rapidly degraded during maturation of messenger RNA. Most genes in the nuclei of eukaryotes contain introns, as do mitochondrial and chloroplast genes. [NIH] Invasive: 1. Having the quality of invasiveness. 2. Involving puncture or incision of the skin or insertion of an instrument or foreign material into the body; said of diagnostic techniques. [EU]
Invertebrates: Animals that have no spinal column. [NIH] Involuntary: Reaction occurring without intention or volition. [NIH] Ion Channels: Gated, ion-selective glycoproteins that traverse membranes. The stimulus for channel gating can be a membrane potential, drug, transmitter, cytoplasmic messenger, or a mechanical deformation. Ion channels which are integral parts of ionotropic neurotransmitter receptors are not included. [NIH] 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] 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
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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] Isocyanates: Organic compounds that contain the -NCO radical. [NIH] Isoenzyme: Different forms of an enzyme, usually occurring in different tissues. The isoenzymes of a particular enzyme catalyze the same reaction but they differ in some of their properties. [NIH] Isoleucine: An essential branched-chain amino acid found in many proteins. It is an isomer of LEUCINE. It is important in hemoglobin synthesis and regulation of blood sugar and energy levels. [NIH] Isothiocyanates: Organic compounds with the general formula R-NCS. [NIH] Isozymes: The multiple forms of a single enzyme. [NIH] Jaundice: A clinical manifestation of hyperbilirubinemia, consisting of deposition of bile pigments in the skin, resulting in a yellowish staining of the skin and mucous membranes. [NIH]
Joint: The point of contact between elements of an animal skeleton with the parts that surround and support it. [NIH] Kallidin: A decapeptide bradykinin homolog produced by the action of tissue and glandular kallikreins on low-molecular-weight kininogen. It is a smooth-muscle stimulant and hypotensive agent that functions through vasodilatation. [NIH] Kava: Dried rhizome and roots of Piper methysticum, a shrub native to Oceania and known for its anti-anxiety and sedative properties. Heavy usage results in some adverse effects. It contains alkaloids, lactones, kawain, methysticin, mucilage, starch, and yangonin. Kava is also the name of the pungent beverage prepared from the plant's roots. [NIH] Kb: A measure of the length of DNA fragments, 1 Kb = 1000 base pairs. The largest DNA fragments are up to 50 kilobases long. [NIH] Keratin: A class of fibrous proteins or scleroproteins important both as structural proteins and as keys to the study of protein conformation. The family represents the principal constituent of epidermis, hair, nails, horny tissues, and the organic matrix of tooth enamel. Two major conformational groups have been characterized, alpha-keratin, whose peptide backbone forms an alpha-helix, and beta-keratin, whose backbone forms a zigzag or pleated sheet structure. [NIH] Keratinocytes: Epidermal cells which synthesize keratin and undergo characteristic changes as they move upward from the basal layers of the epidermis to the cornified (horny) layer of the skin. Successive stages of differentiation of the keratinocytes forming the epidermal layers are basal cell, spinous or prickle cell, and the granular cell. [NIH] Keto: It consists of 8 carbon atoms and within the endotoxins, it connects poysaccharide and lipid A. [NIH]
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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] 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] Kidney Transplantation: The transference of a kidney from one human or animal to another. [NIH] Killer Cells: Lymphocyte-like effector cells which mediate antibody-dependent cell cytotoxicity. They kill antibody-coated target cells which they bind with their Fc receptors. [NIH]
Kinetic: Pertaining to or producing motion. [EU] Labile: 1. Gliding; moving from point to point over the surface; unstable; fluctuating. 2. Chemically unstable. [EU] Labyrinth: The internal ear; the essential part of the organ of hearing. It consists of an osseous and a membranous portion. [NIH] Lac Operon: The genetic unit consisting of three structural genes, an operator and a regulatory gene, which controls the synthesis of beta-galactosidase, beta-galactoside permease, and beta-thiogalactoside acetyltransferase. It includes the structural gene lac Z (lacZ) of Escherichia coli. [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] Large cell carcinomas: A group of lung cancers in which the cells are large and look abnormal when viewed under a microscope. [NIH] Large Intestine: The part of the intestine that goes from the cecum to the rectum. The large intestine absorbs water from stool and changes it from a liquid to a solid form. The large intestine is 5 feet long and includes the appendix, cecum, colon, and rectum. Also called colon. [NIH] Laryngeal: Having to do with the larynx. [NIH] Larynx: An irregularly shaped, musculocartilaginous tubular structure, lined with mucous membrane, located at the top of the trachea and below the root of the tongue and the hyoid bone. It is the essential sphincter guarding the entrance into the trachea and functioning secondarily as the organ of voice. [NIH] Laser therapy: The use of an intensely powerful beam of light to kill cancer cells. [NIH] Latency: The period of apparent inactivity between the time when a stimulus is presented and the moment a response occurs. [NIH] Latent: Phoria which occurs at one distance or another and which usually has no troublesome effect. [NIH]
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Lavage: A cleaning of the stomach and colon. Uses a special drink and enemas. [NIH] Laxative: An agent that acts to promote evacuation of the bowel; a cathartic or purgative. [EU]
Least-Squares Analysis: A principle of estimation in which the estimates of a set of parameters in a statistical model are those quantities minimizing the sum of squared differences between the observed values of a dependent variable and the values predicted by the model. [NIH] Lens: The transparent, double convex (outward curve on both sides) structure suspended between the aqueous and vitreous; helps to focus light on the retina. [NIH] Lesion: An area of abnormal tissue change. [NIH] Lethal: Deadly, fatal. [EU] 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]
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] Levo: It is an experimental treatment for heroin addiction that was developed by German scientists around 1948 as an analgesic. Like methadone, it binds with opioid receptors, but it is longer acting. [NIH] Library Services: Services offered to the library user. They include reference and circulation. [NIH]
Life cycle: The successive stages through which an organism passes from fertilized ovum or spore to the fertilized ovum or spore of the next generation. [NIH] 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] Ligase: An enzyme that repairs single stranded discontinuities in double-stranded DNA molecules in the cell. Purified DNA ligase is used in gene cloning to join DNA molecules together. [NIH] Ligation: Application of a ligature to tie a vessel or strangulate a part. [NIH] Likelihood Functions: Functions constructed from a statistical model and a set of observed data which give the probability of that data for various values of the unknown model parameters. Those parameter values that maximize the probability are the maximum
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likelihood estimates of the parameters. [NIH] Linear Models: Statistical models in which the value of a parameter for a given value of a factor is assumed to be equal to a + bx, where a and b are constants. The models predict a linear regression. [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] Lipase: An enzyme of the hydrolase class that catalyzes the reaction of triacylglycerol and water to yield diacylglycerol and a fatty acid anion. It is produced by glands on the tongue and by the pancreas and initiates the digestion of dietary fats. (From Dorland, 27th ed) EC 3.1.1.3. [NIH] Lipid: Fat. [NIH] Lipid A: Lipid A is the biologically active component of lipopolysaccharides. It shows strong endotoxic activity and exhibits immunogenic properties. [NIH] Lipid Bilayers: Layers of lipid molecules which are two molecules thick. Bilayer systems are frequently studied as models of biological membranes. [NIH] Lipid Peroxidation: Peroxidase catalyzed oxidation of lipids using hydrogen peroxide as an electron acceptor. [NIH] Lipid Peroxides: Peroxides produced in the presence of a free radical by the oxidation of unsaturated fatty acids in the cell in the presence of molecular oxygen. The formation of lipid peroxides results in the destruction of the original lipid leading to the loss of integrity of the membranes. They therefore cause a variety of toxic effects in vivo and their formation is considered a pathological process in biological systems. Their formation can be inhibited by antioxidants, such as vitamin E, structural separation or low oxygen tension. [NIH] Lipoamide Dehydrogenase: A flavoprotein that catalyzes the reduction of lipoamide by NADH to yield dihydrolipoamide and NAD+. The enzyme is a component of the multienzyme pyruvate dehydrogenase complex and 2-oxoglutarate dehydrogenase complex. EC 1.8.1.4. [NIH] Lipopolysaccharide: Substance consisting of polysaccaride and lipid. [NIH] Lipoprotein: Any of the lipid-protein complexes in which lipids are transported in the blood; lipoprotein particles consist of a spherical hydrophobic core of triglycerides or cholesterol esters surrounded by an amphipathic monolayer of phospholipids, cholesterol, and apolipoproteins; the four principal classes are high-density, low-density, and very-lowdensity lipoproteins and chylomicrons. [EU] Lipoxygenase: An enzyme of the oxidoreductase class that catalyzes reactions between linoleate and other fatty acids and oxygen to form hydroperoxy-fatty acid derivatives. Related enzymes in this class include the arachidonate lipoxygenases, arachidonate 5lipoxygenase, arachidonate 12-lipoxygenase, and arachidonate 15-lipoxygenase. EC 1.13.11.12. [NIH] Liver: A large, glandular organ located in the upper abdomen. The liver cleanses the blood and aids in digestion by secreting bile. [NIH] Liver cancer: A disease in which malignant (cancer) cells are found in the tissues of the liver. [NIH]
Liver Transplantation: The transference of a part of or an entire liver from one human or animal to another. [NIH] Lobe: A portion of an organ such as the liver, lung, breast, or brain. [NIH]
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Localization: The process of determining or marking the location or site of a lesion or disease. May also refer to the process of keeping a lesion or disease in a specific location or site. [NIH] Localized: Cancer which has not metastasized yet. [NIH] Locomotion: Movement or the ability to move from one place or another. It can refer to humans, vertebrate or invertebrate animals, and microorganisms. [NIH] Logistic Models: Statistical models which describe the relationship between a qualitative dependent variable (that is, one which can take only certain discrete values, such as the presence or absence of a disease) and an independent variable. A common application is in epidemiology for estimating an individual's risk (probability of a disease) as a function of a given risk factor. [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] Lubricants: Oily or slippery substances. [NIH] Lubrication: The application of a substance to diminish friction between two surfaces. It may refer to oils, greases, and similar substances for the lubrication of medical equipment but it can be used for the application of substances to tissue to reduce friction, such as lotions for skin and vaginal lubricants. [NIH] Lupus: A form of cutaneous tuberculosis. It is seen predominantly in women and typically involves the nasal, buccal, and conjunctival mucosa. [NIH] Lymph: The almost colorless fluid that travels through the lymphatic system and carries cells that help fight infection and disease. [NIH] Lymph node: A rounded mass of lymphatic tissue that is surrounded by a capsule of connective tissue. Also known as a lymph gland. Lymph nodes are spread out along lymphatic vessels and contain many lymphocytes, which filter the lymphatic fluid (lymph). [NIH]
Lymphatic: The tissues and organs, including the bone marrow, spleen, thymus, and lymph nodes, that produce and store cells that fight infection and disease. [NIH] Lymphatic system: The tissues and organs that produce, store, and carry white blood cells that fight infection and other diseases. This system includes the bone marrow, spleen, thymus, lymph nodes and a network of thin tubes that carry lymph and white blood cells. These tubes branch, like blood vessels, into all the tissues of the body. [NIH] Lymphoblastic: One of the most aggressive types of non-Hodgkin lymphoma. [NIH] Lymphoblasts: Interferon produced predominantly by leucocyte cells. [NIH] Lymphocyte: A white blood cell. Lymphocytes have a number of roles in the immune system, including the production of antibodies and other substances that fight infection and diseases. [NIH] Lymphoid: Referring to lymphocytes, a type of white blood cell. Also refers to tissue in which lymphocytes develop. [NIH] Lymphoma: A general term for various neoplastic diseases of the lymphoid tissue. [NIH] Lymphoproliferative: Disorders characterized by proliferation of lymphoid tissue, general or unspecified. [NIH] Lymphoproliferative Disorders: Disorders characterized by proliferation of lymphoid tissue, general or unspecified. [NIH]
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Lysine: An essential amino acid. It is often added to animal feed. [NIH] Lytic: 1. Pertaining to lysis or to a lysin. 2. Producing lysis. [EU] Macrophage: A type of white blood cell that surrounds and kills microorganisms, removes dead cells, and stimulates the action of other immune system cells. [NIH] 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] Macula: A stain, spot, or thickening. Often used alone to refer to the macula retinae. [EU] Macula Lutea: An oval area in the retina, 3 to 5 mm in diameter, usually located temporal to the superior pole of the eye and slightly below the level of the optic disk. [NIH] Macular Degeneration: Degenerative changes in the macula lutea of the retina. [NIH] 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] Malabsorption: Impaired intestinal absorption of nutrients. [EU] Malignancy: A cancerous tumor that can invade and destroy nearby tissue and spread to other parts of the body. [NIH] Malignant: Cancerous; a growth with a tendency to invade and destroy nearby tissue and spread to other parts of the body. [NIH] Malignant tumor: A tumor capable of metastasizing. [NIH] Malnutrition: A condition caused by not eating enough food or not eating a balanced diet. [NIH]
Malondialdehyde: The dialdehyde of malonic acid. [NIH] Mammary: Pertaining to the mamma, or breast. [EU] Mange: Sarcoptic infestation of human skin, particularly a contagious skin disease caused by invasion of the epidermis with Sarcoptes scabiei. [NIH] Manifest: Being the part or aspect of a phenomenon that is directly observable : concretely expressed in behaviour. [EU] Man-made: Ionizing radiation emitted by artificial or concentrated natural, radioactive material or resulting from the operation of high voltage apparatus, such as X-ray apparatus or particle accelerators, of nuclear reactors, or from nuclear explosions. [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] Meat: The edible portions of any animal used for food including domestic mammals (the major ones being cattle, swine, and sheep) along with poultry, fish, shellfish, and game. [NIH]
Meat Products: Articles of food which are derived by a process of manufacture from any portion of carcasses of any animal used for food (e.g., head cheese, sausage, scrapple). [NIH] Medial: Lying near the midsaggital plane of the body; opposed to lateral. [NIH]
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Mediate: Indirect; accomplished by the aid of an intervening medium. [EU] Mediator: An object or substance by which something is mediated, such as (1) a structure of the nervous system that transmits impulses eliciting a specific response; (2) a chemical substance (transmitter substance) that induces activity in an excitable tissue, such as nerve or muscle; or (3) a substance released from cells as the result of the interaction of antigen with antibody or by the action of antigen with a sensitized lymphocyte. [EU] MEDLINE: An online database of MEDLARS, the computerized bibliographic Medical Literature Analysis and Retrieval System of the National Library of Medicine. [NIH] Medulloblastoma: A malignant brain tumor that begins in the lower part of the brain and can spread to the spine or to other parts of the body. Medulloblastomas are sometimes called primitive neuroectodermal tumors (PNET). [NIH] Megakaryocytes: Very large bone marrow cells which release mature blood platelets. [NIH] Megaloblastic: A large abnormal red blood cell appearing in the blood in pernicious anaemia. [EU] Meiosis: A special method of cell division, occurring in maturation of the germ cells, by means of which each daughter nucleus receives half the number of chromosomes characteristic of the somatic cells of the species. [NIH] Melanin: The substance that gives the skin its color. [NIH] Melanocytes: Epidermal dendritic pigment cells which control long-term morphological color changes by alteration in their number or in the amount of pigment they produce and store in the pigment containing organelles called melanosomes. Melanophores are larger cells which do not exist in mammals. [NIH] Melanoma: A form of skin cancer that arises in melanocytes, the cells that produce pigment. Melanoma usually begins in a mole. [NIH] Melanosomes: Melanin-containing organelles found in melanocytes and melanophores. [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] Memory: Complex mental function having four distinct phases: (1) memorizing or learning, (2) retention, (3) recall, and (4) recognition. Clinically, it is usually subdivided into immediate, recent, and remote memory. [NIH] Meninges: The three membranes that cover and protect the brain and spinal cord. [NIH] Meningitis: Inflammation of the meninges. When it affects the dura mater, the disease is termed pachymeningitis; when the arachnoid and pia mater are involved, it is called leptomeningitis, or meningitis proper. [EU] Menopause: Permanent cessation of menstruation. [NIH] Menorrhagia: Excessive menstrual flow. [NIH] Menstrual Cycle: The period of the regularly recurring physiologic changes in the endometrium occurring during the reproductive period in human females and some primates and culminating in partial sloughing of the endometrium (menstruation). [NIH] Menstruation: The normal physiologic discharge through the vagina of blood and mucosal tissues from the nonpregnant uterus. [NIH] Mental Health: The state wherein the person is well adjusted. [NIH]
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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] Mesencephalic: Ipsilateral oculomotor paralysis and contralateral tremor, spasm. or choreic movements of the face and limbs. [NIH] Mesenchymal: Refers to cells that develop into connective tissue, blood vessels, and lymphatic tissue. [NIH] Metabolite: Any substance produced by metabolism or by a metabolic process. [EU] Metallothionein: A low-molecular-weight (approx. 10 kD) protein occurring in the cytoplasm of kidney cortex and liver. It is rich in cysteinyl residues and contains no aromatic amino acids. Metallothionein shows high affinity for bivalent heavy metals. [NIH] Metaphase: The second phase of cell division, in which the chromosomes line up across the equatorial plane of the spindle prior to separation. [NIH] Metaplasia: A condition in which there is a change of one adult cell type to another similar adult cell type. [NIH] Metastasis: The spread of cancer from one part of the body to another. Tumors formed from cells that have spread are called "secondary tumors" and contain cells that are like those in the original (primary) tumor. The plural is metastases. [NIH] Metastatic: Having to do with metastasis, which is the spread of cancer from one part of the body to another. [NIH] Methamphetamine: A central nervous system stimulant and sympathomimetic with actions and uses similar to dextroamphetamine. The smokable form is a drug of abuse and is referred to as crank, crystal, crystal meth, ice, and speed. [NIH] Methionine: A sulfur containing essential amino acid that is important in many body functions. It is a chelating agent for heavy metals. [NIH] Methyltransferase: A drug-metabolizing enzyme. [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] Micromanipulation: The performance of dissections, injections, surgery, etc., by the use of micromanipulators (attachments to a microscope that manipulate tiny instruments). [NIH] Micromanipulators: A high precision instrument used in microinjection or chromosome dissection activities. [NIH] Micronuclei: Nuclei, separate from and additional to the main nucleus of a cell, produced during the telophase of mitosis or meiosis by lagging chromosomes or chromosome fragments derived from spontaneous or experimentally induced chromosomal structural changes. This concept also includes the smaller, reproductive nuclei found in multinucleate protozoans. [NIH] Microorganism: An organism that can be seen only through a microscope. Microorganisms
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include bacteria, protozoa, algae, and fungi. Although viruses are not considered living organisms, they are sometimes classified as microorganisms. [NIH] Microscopy: The application of microscope magnification to the study of materials that cannot be properly seen by the unaided eye. [NIH] Microsomal: Of or pertaining to microsomes : vesicular fragments of endoplasmic reticulum formed after disruption and centrifugation of cells. [EU] Microtubule-Associated Proteins: High molecular weight proteins found in the microtubules of the cytoskeletal system. Under certain conditions they are required for tubulin assembly into the microtubules and stabilize the assembled microtubules. [NIH] Microtubules: Slender, cylindrical filaments found in the cytoskeleton of plant and animal cells. They are composed of the protein tubulin. [NIH] Migration: The systematic movement of genes between populations of the same species, geographic race, or variety. [NIH] Milk Thistle: The plant Silybum marianum in the family Asteraceae containing the bioflavonoid complex silymarin. For centuries this has been used traditionally to treat liver disease. [NIH] Milligram: A measure of weight. A milligram is approximately 450,000-times smaller than a pound and 28,000-times smaller than an ounce. [NIH] Mitochondria: Parts of a cell where aerobic production (also known as cell respiration) takes place. [NIH] Mitochondrial Swelling: Increase in volume of mitochondria due to an influx of fluid; it occurs in hypotonic solutions due to osmotic pressure and in isotonic solutions as a result of altered permeability of the membranes of respiring mitochondria. [NIH] Mitosis: A method of indirect cell division by means of which the two daughter nuclei normally receive identical complements of the number of chromosomes of the somatic cells of the species. [NIH] Mobility: Capability of movement, of being moved, or of flowing freely. [EU] Modeling: A treatment procedure whereby the therapist presents the target behavior which the learner is to imitate and make part of his repertoire. [NIH] Modification: A change in an organism, or in a process in an organism, that is acquired from its own activity or environment. [NIH] Modulator: A specific inductor that brings out characteristics peculiar to a definite region. [EU]
Molecular: Of, pertaining to, or composed of molecules : a very small mass of matter. [EU] Molecular mass: The sum of the atomic masses of all atoms in a molecule, based on a scale in which the atomic masses of hydrogen, carbon, nitrogen, and oxygen are 1, 12, 14, and 16, respectively. For example, the molecular mass of water, which has two atoms of hydrogen and one atom of oxygen, is 18 (i.e., 2 + 16). [NIH] Molecular Structure: The location of the atoms, groups or ions relative to one another in a molecule, as well as the number, type and location of covalent bonds. [NIH] Molecule: A chemical made up of two or more atoms. The atoms in a molecule can be the same (an oxygen molecule has two oxygen atoms) or different (a water molecule has two hydrogen atoms and one oxygen atom). Biological molecules, such as proteins and DNA, can be made up of many thousands of atoms. [NIH] Monitor: An apparatus which automatically records such physiological signs as respiration, pulse, and blood pressure in an anesthetized patient or one undergoing surgical or other
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procedures. [NIH] Monoclonal: An antibody produced by culturing a single type of cell. It therefore consists of a single species of immunoglobulin molecules. [NIH] Monoclonal antibodies: Laboratory-produced substances that can locate and bind to cancer cells wherever they are in the body. Many monoclonal antibodies are used in cancer detection or therapy; each one recognizes a different protein on certain cancer cells. Monoclonal antibodies can be used alone, or they can be used to deliver drugs, toxins, or radioactive material directly to a tumor. [NIH] Monocyte: A type of white blood cell. [NIH] Mononuclear: A cell with one nucleus. [NIH] 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] Motion Sickness: Sickness caused by motion, as sea sickness, train sickness, car sickness, and air sickness. [NIH] Mucins: A secretion containing mucopolysaccharides and protein that is the chief constituent of mucus. [NIH] Mucolytic: Destroying or dissolving mucin; an agent that so acts : a mucopolysaccharide or glycoprotein, the chief constituent of mucus. [EU] Mucosa: A mucous membrane, or tunica mucosa. [EU] Mucus: The viscous secretion of mucous membranes. It contains mucin, white blood cells, water, inorganic salts, and exfoliated cells. [NIH] Multidrug resistance: Adaptation of tumor cells to anticancer drugs in ways that make the drugs less effective. [NIH] 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] Multiple sclerosis: A disorder of the central nervous system marked by weakness, numbness, a loss of muscle coordination, and problems with vision, speech, and bladder control. Multiple sclerosis is thought to be an autoimmune disease in which the body's immune system destroys myelin. Myelin is a substance that contains both protein and fat (lipid) and serves as a nerve insulator and helps in the transmission of nerve signals. [NIH] Muscle Fibers: Large single cells, either cylindrical or prismatic in shape, that form the basic unit of muscle tissue. They consist of a soft contractile substance enclosed in a tubular sheath. [NIH] 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] Mustard Gas: Severe irritant and vesicant of skin, eyes, and lungs. It may cause blindness and lethal lung edema and was formerly used as a war gas. The substance has been proposed as a cytostatic and for treatment of psoriasis. It has been listed as a known carcinogen in the Fourth Annual Report on Carcinogens (NTP-85-002, 1985) (Merck, 11th ed). [NIH]
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Mutagen: Any agent, such as X-rays, gamma rays, mustard gas, TCDD, that can cause abnormal mutation in living cells; having the power to cause mutations. [NIH] Mutagenesis: Process of generating genetic mutations. It may occur spontaneously or be induced by mutagens. [NIH] Mutagenic: Inducing genetic mutation. [EU] Mutagenicity: Ability to damage DNA, the genetic material; the power to cause mutations. [NIH]
Myasthenia: Muscular debility; any constitutional anomaly of muscle. [EU] Mycotoxins: Toxins derived from bacteria or fungi. [NIH] Mydriatic: 1. Dilating the pupil. 2. Any drug that dilates the pupil. [EU] Myelin: The fatty substance that covers and protects nerves. [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] Myristate: Pharmacological activator of protein kinase C. [NIH] N-acetyl: Analgesic agent. [NIH] Narcotic: 1. Pertaining to or producing narcosis. 2. An agent that produces insensibility or stupor, applied especially to the opioids, i.e. to any natural or synthetic drug that has morphine-like actions. [EU] Natural killer cells: NK cells. A type of white blood cell that contains granules with enzymes that can kill tumor cells or microbial cells. Also called large granular lymphocytes (LGL). [NIH] Natural selection: A part of the evolutionary process resulting in the survival and reproduction of the best adapted individuals. [NIH] Nausea: An unpleasant sensation in the stomach usually accompanied by the urge to vomit. Common causes are early pregnancy, sea and motion sickness, emotional stress, intense pain, food poisoning, and various enteroviruses. [NIH] NCI: National Cancer Institute. NCI, part of the National Institutes of Health of the United States Department of Health and Human Services, is the federal government's principal agency for cancer research. NCI conducts, coordinates, and funds cancer research, training, health information dissemination, and other programs with respect to the cause, diagnosis, prevention, and treatment of cancer. Access the NCI Web site at http://cancer.gov. [NIH] Necrosis: A pathological process caused by the progressive degradative action of enzymes that is generally associated with severe cellular trauma. It is characterized by mitochondrial swelling, nuclear flocculation, uncontrolled cell lysis, and ultimately cell death. [NIH]
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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] Nematocide: A chemical used to kill nematodes. [NIH] Neocortex: The largest portion of the cerebral cortex. It is composed of neurons arranged in six layers. [NIH] Neonatal: Pertaining to the first four weeks after birth. [EU] Neoplasia: Abnormal and uncontrolled cell growth. [NIH] Neoplasm: A new growth of benign or malignant tissue. [NIH] Neoplastic: Pertaining to or like a neoplasm (= any new and abnormal growth); pertaining to neoplasia (= the formation of a neoplasm). [EU] Nephropathy: Disease of the kidneys. [EU] Nerve: A cordlike structure of nervous tissue that connects parts of the nervous system with other tissues of the body and conveys nervous impulses to, or away from, these tissues. [NIH] Nervous System: The entire nerve apparatus composed of the brain, spinal cord, nerves and ganglia. [NIH] Neural: 1. Pertaining to a nerve or to the nerves. 2. Situated in the region of the spinal axis, as the neutral arch. [EU] Neuroblastoma: Cancer that arises in immature nerve cells and affects mostly infants and children. [NIH] Neurodegenerative Diseases: Hereditary and sporadic conditions which are characterized by progressive nervous system dysfunction. These disorders are often associated with atrophy of the affected central or peripheral nervous system structures. [NIH] Neurofibrillary Tangles: Abnormal structures located in various parts of the brain and composed of dense arrays of paired helical filaments (neurofilaments and microtubules). These double helical stacks of transverse subunits are twisted into left-handed ribbon-like filaments that likely incorporate the following proteins: (1) the intermediate filaments: medium- and high-molecular-weight neurofilaments; (2) the microtubule-associated proteins map-2 and tau; (3) actin; and (4) ubiquitin. As one of the hallmarks of Alzheimer disease, the neurofibrillary tangles eventually occupy the whole of the cytoplasm in certain classes of cell in the neocortex, hippocampus, brain stem, and diencephalon. The number of these tangles, as seen in post mortem histology, correlates with the degree of dementia during life. Some studies suggest that tangle antigens leak into the systemic circulation both in the course of normal aging and in cases of Alzheimer disease. [NIH] Neurofilaments: Bundle of neuronal fibers. [NIH] Neurologic: Having to do with nerves or the nervous system. [NIH] Neurology: A medical specialty concerned with the study of the structures, functions, and diseases of the nervous system. [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
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neurotransmitters and some functioning as hormones. [NIH] Neurophysiology: The scientific discipline concerned with the physiology of the nervous system. [NIH] Neurotoxic: Poisonous or destructive to nerve tissue. [EU] Neurotoxicity: The tendency of some treatments to cause damage to the nervous system. [NIH]
Neurotransmitters: Endogenous signaling molecules that alter the behavior of neurons or effector cells. Neurotransmitter is used here in its most general sense, including not only messengers that act directly to regulate ion channels, but also those that act through second messenger systems, and those that act at a distance from their site of release. Included are neuromodulators, neuroregulators, neuromediators, and neurohumors, whether or not acting at synapses. [NIH] Neutrons: Electrically neutral elementary particles found in all atomic nuclei except light hydrogen; the mass is equal to that of the proton and electron combined and they are unstable when isolated from the nucleus, undergoing beta decay. Slow, thermal, epithermal, and fast neutrons refer to the energy levels with which the neutrons are ejected from heavier nuclei during their decay. [NIH] Neutropenia: An abnormal decrease in the number of neutrophils, a type of white blood cell. [NIH] Neutrophil: A type of white blood cell. [NIH] Nicardipine: 1,4-Dihydro-2,6-dimethyl-4-(3-nitrophenyl) methyl 2(methyl(phenylmethyl)amino)-3,5-pyridinecarboxylic acid ethyl ester. A potent calcium channel blockader with marked vasodilator action. It has antihypertensive properties and is effective in the treatment of angina and coronary spasms without showing cardiodepressant effects. It has also been used in the treatment of asthma and enhances the action of specific antineoplastic agents. [NIH] Nicotine: Nicotine is highly toxic alkaloid. It is the prototypical agonist at nicotinic cholinergic receptors where it dramatically stimulates neurons and ultimately blocks synaptic transmission. Nicotine is also important medically because of its presence in tobacco smoke. [NIH] Nimustine: Antineoplastic agent especially effective against malignant brain tumors. The resistance which brain tumor cells acquire to the initial effectiveness of this drug can be partially overcome by the simultaneous use of membrane-modifying agents such as reserpine, calcium antagonists such as nicardipine or verapamil, or the calmodulin inhibitor, trifluoperazine. The drug has also been used in combination with other antineoplastic agents or with radiotherapy for the treatment of various neoplasms. [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 Compounds: Inorganic compounds that contain nitrogen as an integral part of the
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molecule. [NIH] Nitroglycerin: A highly volatile organic nitrate that acts as a dilator of arterial and venous smooth muscle and is used in the treatment of angina. It provides relief through improvement of the balance between myocardial oxygen supply and demand. Although total coronary blood flow is not increased, there is redistribution of blood flow in the heart when partial occlusion of coronary circulation is effected. [NIH] Nitrosamines: A class of compounds that contain a -NH2 and a -NO radical. Many members of this group have carcinogenic and mutagenic properties. [NIH] Nitrous Oxide: Nitrogen oxide (N2O). A colorless, odorless gas that is used as an anesthetic and analgesic. High concentrations cause a narcotic effect and may replace oxygen, causing death by asphyxia. It is also used as a food aerosol in the preparation of whipping cream. [NIH]
Non-small cell lung cancer: A group of lung cancers that includes squamous cell carcinoma, adenocarcinoma, and large cell carcinoma. [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] Nosocomial: Pertaining to or originating in the hospital, said of an infection not present or incubating prior to admittance to the hospital, but generally occurring 72 hours after admittance; the term is usually used to refer to patient disease, but hospital personnel may also acquire nosocomial infection. [EU] Nuclear: A test of the structure, blood flow, and function of the kidneys. The doctor injects a mildly radioactive solution into an arm vein and uses x-rays to monitor its progress through the kidneys. [NIH] Nuclei: A body of specialized protoplasm found in nearly all cells and containing the chromosomes. [NIH] Nucleic acid: Either of two types of macromolecule (DNA or RNA) formed by polymerization of nucleotides. Nucleic acids are found in all living cells and contain the information (genetic code) for the transfer of genetic information from one generation to the next. [NIH] Nucleic Acid Hybridization: The process whereby two single-stranded polynucleotides form a double-stranded molecule, with hydrogen bonding between the complementary bases in the two strains. [NIH] Nucleus: A body of specialized protoplasm found in nearly all cells and containing the chromosomes. [NIH] Nutritional Status: State of the body in relation to the consumption and utilization of nutrients. [NIH] Occupational Exposure: The exposure to potentially harmful chemical, physical, or biological agents that occurs as a result of one's occupation. [NIH] Ocular: 1. Of, pertaining to, or affecting the eye. 2. Eyepiece. [EU] Oculomotor: Cranial nerve III. It originate from the lower ventral surface of the midbrain and is classified as a motor nerve. [NIH] Odour: A volatile emanation that is perceived by the sense of smell. [EU] Oestrogen: A generic term for oestrus-producing steroid compounds; the female sex
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hormones. In humans, oestrogen is formed in the ovary, possibly the adrenal cortex, the testis, and the foetoplacental unit; it has various functions in both sexes. It is responsible for the development of the female secondary sex characteristics, and during the menstrual cycle it acts on the female genitalia to produce an environment suitable for the fertilization, implantation, and nutrition of the early embryo. Oestrogen is used in oral contraceptives and as a palliative in cancer of the breast after menopause and cancer of the prostate; other uses include the relief of the discomforts of menopause, inhibition of lactation, and treatment of osteoporosis, threatened abortion, and various functional ovarian disorders. [EU]
Ointments: Semisolid preparations used topically for protective emollient effects or as a vehicle for local administration of medications. Ointment bases are various mixtures of fats, waxes, animal and plant oils and solid and liquid hydrocarbons. [NIH] Oltipraz: A drug used in cancer prevention. [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] Oncogenic Viruses: Viruses that produce tumors. [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] Oophoritis: Inflammation of an ovary. [NIH] Opacity: Degree of density (area most dense taken for reading). [NIH] Ophthalmology: A surgical specialty concerned with the structure and function of the eye and the medical and surgical treatment of its defects and diseases. [NIH] Opsin: A protein formed, together with retinene, by the chemical breakdown of metarhodopsin. [NIH] Optic Chiasm: The X-shaped structure formed by the meeting of the two optic nerves. At the optic chiasm the fibers from the medial part of each retina cross to project to the other side of the brain while the lateral retinal fibers continue on the same side. As a result each half of the brain receives information about the contralateral visual field from both eyes. [NIH]
Optic Disk: The portion of the optic nerve seen in the fundus with the ophthalmoscope. It is formed by the meeting of all the retinal ganglion cell axons as they enter the optic nerve. [NIH]
Optic Nerve: The 2nd cranial nerve. The optic nerve conveys visual information from the retina to the brain. The nerve carries the axons of the retinal ganglion cells which sort at the optic chiasm and continue via the optic tracts to the brain. The largest projection is to the lateral geniculate nuclei; other important targets include the superior colliculi and the suprachiasmatic nuclei. Though known as the second cranial nerve, it is considered part of the central nervous system. [NIH] Optic nerve head: The circular area (disc) where the optic nerve connects to the retina. [NIH] 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 Preservation: The process by which organs are kept viable outside of the organism from which they were removed (i.e., kept from decay by means of a chemical agent, cooling,
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or a fluid substitute that mimics the natural state within the organism). [NIH] Organ Preservation Solutions: Solutions used to store organs, particulary those awaiting implantation. [NIH] Organelles: Specific particles of membrane-bound organized living substances present in eukaryotic cells, such as the mitochondria; the golgi apparatus; endoplasmic reticulum; lysomomes; plastids; and vacuoles. [NIH] Orgasm: The crisis of sexual excitement in either humans or animals. [NIH] 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] Osteoporosis: Reduction of bone mass without alteration in the composition of bone, leading to fractures. Primary osteoporosis can be of two major types: postmenopausal osteoporosis and age-related (or senile) osteoporosis. [NIH] Ototoxic: Having a deleterious effect upon the eighth nerve, or upon the organs of hearing and balance. [EU] Outpatient: A patient who is not an inmate of a hospital but receives diagnosis or treatment in a clinic or dispensary connected with the hospital. [NIH] Ovaries: The pair of female reproductive glands in which the ova, or eggs, are formed. The ovaries are located in the pelvis, one on each side of the uterus. [NIH] Ovary: Either of the paired glands in the female that produce the female germ cells and secrete some of the female sex hormones. [NIH] Overdose: An accidental or deliberate dose of a medication or street drug that is in excess of what is normally used. [NIH] Overexpress: An excess of a particular protein on the surface of a cell. [NIH] Ovum: A female germ cell extruded from the ovary at ovulation. [NIH] Oxaliplatin: An anticancer drug that belongs to the family of drugs called platinum compounds. [NIH] Oxidants: Oxidizing agents or electron-accepting molecules in chemical reactions in which electrons are transferred from one molecule to another (oxidation-reduction). In vivo, it appears that phagocyte-generated oxidants function as tumor promoters or cocarcinogens rather than as complete carcinogens perhaps because of the high levels of endogenous antioxidant defenses. It is also thought that oxidative damage in joints may trigger the autoimmune response that characterizes the persistence of the rheumatoid disease process. [NIH]
Oxidation: The act of oxidizing or state of being oxidized. Chemically it consists in the increase of positive charges on an atom or the loss of negative charges. Most biological oxidations are accomplished by the removal of a pair of hydrogen atoms (dehydrogenation) from a molecule. Such oxidations must be accompanied by reduction of an acceptor molecule. Univalent o. indicates loss of one electron; divalent o., the loss of two electrons. [EU]
Oxidation-Reduction: A chemical reaction in which an electron is transferred from one molecule to another. The electron-donating molecule is the reducing agent or reductant; the electron-accepting molecule is the oxidizing agent or oxidant. Reducing and oxidizing agents function as conjugate reductant-oxidant pairs or redox pairs (Lehninger, Principles of Biochemistry, 1982, p471). [NIH] Oxidative metabolism: A chemical process in which oxygen is used to make energy from
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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] Oxygenase: Enzyme which breaks down heme, the iron-containing oxygen-carrying constituent of the red blood cells. [NIH] Paclitaxel: Antineoplastic agent isolated from the bark of the Pacific yew tree, Taxus brevifolia. Paclitaxel stabilizes microtubules in their polymerized form and thus mimics the action of the proto-oncogene proteins c-mos. [NIH] Palliative: 1. Affording relief, but not cure. 2. An alleviating medicine. [EU] Palpitation: A subjective sensation of an unduly rapid or irregular heart beat. [EU] 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] Papilla: A small nipple-shaped elevation. [NIH] Papillary: Pertaining to or resembling papilla, or nipple. [EU] Papovaviridae: A family of small, non-enveloped DNA viruses affecting mostly mammals. Most members can induce tumors in hosts. There are two genera: Papillomavirus and Polyomavirus. [NIH] Paraffin: A mixture of solid hydrocarbons obtained from petroleum. It has a wide range of uses including as a stiffening agent in ointments, as a lubricant, and as a topical antiinflammatory. It is also commonly used as an embedding material in histology. [NIH] Paralysis: Loss of ability to move all or part of the body. [NIH] Parasite: An animal or a plant that lives on or in an organism of another species and gets at least some of its nutrition from that other organism. [NIH] Parathyroid: 1. Situated beside the thyroid gland. 2. One of the parathyroid glands. 3. A sterile preparation of the water-soluble principle(s) of the parathyroid glands, ad-ministered parenterally as an antihypocalcaemic, especially in the treatment of acute hypoparathyroidism with tetany. [EU] Parathyroid Glands: Two small paired endocrine glands in the region of the thyroid gland. They secrete parathyroid hormone and are concerned with the metabolism of calcium and phosphorus. [NIH] Parathyroid hormone: A substance made by the parathyroid gland that helps the body store and use calcium. Also called parathormone, parathyrin, or PTH. [NIH] Parenteral: Not through the alimentary canal but rather by injection through some other route, as subcutaneous, intramuscular, intraorbital, intracapsular, intraspinal, intrasternal,
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intravenous, etc. [EU] Parkinsonism: A group of neurological disorders characterized by hypokinesia, tremor, and muscular rigidity. [EU] Parotid: The space that contains the parotid gland, the facial nerve, the external carotid artery, and the retromandibular vein. [NIH] Paroxysmal: Recurring in paroxysms (= spasms or seizures). [EU] Partial remission: The shrinking, but not complete disappearance, of a tumor in response to therapy. Also called partial response. [NIH] Particle: A tiny mass of material. [EU] Patch: A piece of material used to cover or protect a wound, an injured part, etc.: a patch over the eye. [NIH] Pathogen: Any disease-producing microorganism. [EU] Pathogenesis: The cellular events and reactions that occur in the development of disease. [NIH]
Pathologic: 1. Indicative of or caused by a morbid condition. 2. Pertaining to pathology (= branch of medicine that treats the essential nature of the disease, especially the structural and functional changes in tissues and organs of the body caused by the disease). [EU] Pathologic Processes: The abnormal mechanisms and forms involved in the dysfunctions of tissues and organs. [NIH] Pathologies: The study of abnormality, especially the study of diseases. [NIH] Pathophysiology: Altered functions in an individual or an organ due to disease. [NIH] Pelvic: Pertaining to the pelvis. [EU] Penicillin: An antibiotic drug used to treat infection. [NIH] Penis: The external reproductive organ of males. It is composed of a mass of erectile tissue enclosed in three cylindrical fibrous compartments. Two of the three compartments, the corpus cavernosa, are placed side-by-side along the upper part of the organ. The third compartment below, the corpus spongiosum, houses the urethra. [NIH] Pepsin: An enzyme made in the stomach that breaks down proteins. [NIH] Peptide: Any compound consisting of two or more amino acids, the building blocks of proteins. Peptides are combined to make proteins. [NIH] Peptide T: N-(N-(N(2)-(N-(N-(N-(N-D-Alanyl L-seryl)-L-threonyl)-L-threonyl) L-threonyl)L-asparaginyl)-L-tyrosyl) L-threonine. Octapeptide sharing sequence homology with HIV envelope protein gp120. It is potentially useful as antiviral agent in AIDS therapy. The core pentapeptide sequence, TTNYT, consisting of amino acids 4-8 in peptide T, is the HIV envelope sequence required for attachment to the CD4 receptor. [NIH] Perennial: Lasting through the year of for several years. [EU] Perforation: 1. The act of boring or piercing through a part. 2. A hole made through a part or substance. [EU] 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
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and ending 7 to 28 days after birth. [EU] Periodontal disease: Disease involving the supporting structures of the teeth (as the gums and periodontal membranes). [NIH] Periodontitis: Inflammation of the periodontal membrane; also called periodontitis simplex. [NIH]
Peripheral Nervous System: The nervous system outside of the brain and spinal cord. The peripheral nervous system has autonomic and somatic divisions. The autonomic nervous system includes the enteric, parasympathetic, and sympathetic subdivisions. The somatic nervous system includes the cranial and spinal nerves and their ganglia and the peripheral sensory receptors. [NIH] Peripheral Vascular Disease: Disease in the large blood vessels of the arms, legs, and feet. People who have had diabetes for a long time may get this because major blood vessels in their arms, legs, and feet are blocked and these limbs do not receive enough blood. The signs of PVD are aching pains in the arms, legs, and feet (especially when walking) and foot sores that heal slowly. Although people with diabetes cannot always avoid PVD, doctors say they have a better chance of avoiding it if they take good care of their feet, do not smoke, and keep both their blood pressure and diabetes under good control. [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] Peritonitis: Inflammation of the peritoneum; a condition marked by exudations in the peritoneum of serum, fibrin, cells, and pus. It is attended by abdominal pain and tenderness, constipation, vomiting, and moderate fever. [EU] Peroxidase: A hemeprotein from leukocytes. Deficiency of this enzyme leads to a hereditary disorder coupled with disseminated moniliasis. It catalyzes the conversion of a donor and peroxide to an oxidized donor and water. EC 1.11.1.7. [NIH] Peroxide: Chemical compound which contains an atom group with two oxygen atoms tied to each other. [NIH] Peroxisome Proliferators: A class of nongenotoxic carcinogens that induce the production of hepatic peroxisomes and induce hepatic neoplasms after long-term administration. [NIH] Pertussis: An acute, highly contagious infection of the respiratory tract, most frequently affecting young children, usually caused by Bordetella pertussis; a similar illness has been associated with infection by B. parapertussis and B. bronchiseptica. It is characterized by a catarrhal stage, beginning after an incubation period of about two weeks, with slight fever, sneezing, running at the nose, and a dry cough. In a week or two the paroxysmal stage begins, with the characteristic paroxysmal cough, consisting of a deep inspiration, followed by a series of quick, short coughs, continuing until the air is expelled from the lungs; the close of the paroxysm is marked by a long-drawn, shrill, whooping inspiration, due to spasmodic closure of the glottis. This stage lasts three to four weeks, after which the convalescent stage begins, in which paroxysms grow less frequent and less violent, and finally cease. Called also whooping cough. [EU] Petroleum: Naturally occurring complex liquid hydrocarbons which, after distillation, yield
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combustible fuels, petrochemicals, and lubricants. [NIH] P-Glycoprotein: A 170 kD transmembrane glycoprotein from the superfamily of ABC transporters. It serves as an ATP-dependent efflux pump for a variety of chemicals, including many antineoplastic agents. Overexpression of this glycoprotein is associated with multidrug resistance. [NIH] Phagocyte: An immune system cell that can surround and kill microorganisms and remove dead cells. Phagocytes include macrophages. [NIH] Phallic: Pertaining to the phallus, or penis. [EU] 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] Pharmacokinetic: The mathematical analysis of the time courses of absorption, distribution, and elimination of drugs. [NIH] Pharmacologic: Pertaining to pharmacology or to the properties and reactions of drugs. [EU] Pharynx: The hollow tube about 5 inches long that starts behind the nose and ends at the top of the trachea (windpipe) and esophagus (the tube that goes to the stomach). [NIH] Phenobarbital: A barbituric acid derivative that acts as a nonselective central nervous system depressant. It promotes binding to inhibitory GABA subtype receptors, and modulates chloride currents through receptor channels. It also inhibits glutamate induced depolarizations. [NIH] Phenotype: The outward appearance of the individual. It is the product of interactions between genes and between the genotype and the environment. This includes the killer phenotype, characteristic of yeasts. [NIH] Phenyl: Ingredient used in cold and flu remedies. [NIH] Phenylalanine: An aromatic amino acid that is essential in the animal diet. It is a precursor of melanin, dopamine, noradrenalin, and thyroxine. [NIH] Phorbol: Class of chemicals that promotes the development of tumors. [NIH] 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] Phosphorous: Having to do with or containing the element phosphorus. [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
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grown in the eye. This is the main treatment for diabetic retinopathy. [NIH] Photodynamic therapy: Treatment with drugs that become active when exposed to light. These drugs kill cancer cells. [NIH] Photosensitivity: An abnormal cutaneous response involving the interaction between photosensitizing substances and sunlight or filtered or artificial light at wavelengths of 280400 mm. There are two main types : photoallergy and photoxicity. [EU] Phototherapy: Treatment of disease by exposure to light, especially by variously concentrated light rays or specific wavelengths. [NIH] Phylogeny: The relationships of groups of organisms as reflected by their evolutionary history. [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 cells, tissues, and organs. [NIH] Pigment: A substance that gives color to tissue. Pigments are responsible for the color of skin, eyes, and hair. [NIH] Pilot study: The initial study examining a new method or treatment. [NIH] Pituitary Gland: A small, unpaired gland situated in the sella turcica tissue. It is connected to the hypothalamus by a short stalk. [NIH] Placenta: A highly vascular fetal organ through which the fetus absorbs oxygen and other nutrients and excretes carbon dioxide and other wastes. It begins to form about the eighth day of gestation when the blastocyst adheres to the decidua. [NIH] Plana: The radiographic term applied to a vertebral body crushed to a thin plate. [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] Plastic surgeon: A surgeon who specializes in reducing scarring or disfigurement that may occur as a result of accidents, birth defects, or treatment for diseases. [NIH]
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Plastids: Self-replicating cytoplasmic organelles of plant and algal cells that contain pigments and may synthesize and accumulate various substances. Plastids are used in phylogenetic studies. [NIH] Platelet Activation: A series of progressive, overlapping events triggered by exposure of the platelets to subendothelial tissue. These events include shape change, adhesiveness, aggregation, and release reactions. When carried through to completion, these events lead to the formation of a stable hemostatic plug. [NIH] Platelet Aggregation: The attachment of platelets to one another. This clumping together can be induced by a number of agents (e.g., thrombin, collagen) and is part of the mechanism leading to the formation of a thrombus. [NIH] Platelets: A type of blood cell that helps prevent bleeding by causing blood clots to form. Also called thrombocytes. [NIH] Platinum: Platinum. A heavy, soft, whitish metal, resembling tin, atomic number 78, atomic weight 195.09, symbol Pt. (From Dorland, 28th ed) It is used in manufacturing equipment for laboratory and industrial use. It occurs as a black powder (platinum black) and as a spongy substance (spongy platinum) and may have been known in Pliny's time as "alutiae". [NIH]
Platinum Compounds: Inorganic compounds which contain platinum as the central atom. [NIH]
Pneumoconiosis: Condition characterized by permanent deposition of substantial amounts of particulate matter in the lungs, usually of occupational or environmental origin, and by the tissue reaction to its presence. [NIH] Poisoning: A condition or physical state produced by the ingestion, injection or inhalation of, or exposure to a deleterious agent. [NIH] Pollen: The male fertilizing element of flowering plants analogous to sperm in animals. It is released from the anthers as yellow dust, to be carried by insect or other vectors, including wind, to the ovary (stigma) of other flowers to produce the embryo enclosed by the seed. The pollens of many plants are allergenic. [NIH] Polyarthritis: An inflammation of several joints together. [EU] Polycystic: An inherited disorder characterized by many grape-like clusters of fluid-filled cysts that make both kidneys larger over time. These cysts take over and destroy working kidney tissue. PKD may cause chronic renal failure and end-stage renal disease. [NIH] Polyethylene: A vinyl polymer made from ethylene. It can be branched or linear. Branched or low-density polyethylene is tough and pliable but not to the same degree as linear polyethylene. Linear or high-density polyethylene has a greater hardness and tensile strength. Polyethylene is used in a variety of products, including implants and prostheses. [NIH]
Polymerase: An enzyme which catalyses the synthesis of DNA using a single DNA strand as a template. The polymerase copies the template in the 5'-3'direction provided that sufficient quantities of free nucleotides, dATP and dTTP are present. [NIH] Polymers: Compounds formed by the joining of smaller, usually repeating, units linked by covalent bonds. These compounds often form large macromolecules (e.g., polypeptides, proteins, plastics). [NIH] Polymorphic: Occurring in several or many forms; appearing in different forms at different stages of development. [EU] Polymorphism: The occurrence together of two or more distinct forms in the same population. [NIH]
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Polyomavirus: A genus of the family papovaviridae consisting of potentially oncogenic viruses normally present in the host as a latent infection. The virus is oncogenic in hosts different from the species of origin. [NIH] Polypeptide: A peptide which on hydrolysis yields more than two amino acids; called tripeptides, tetrapeptides, etc. according to the number of amino acids contained. [EU] Polyposis: The development of numerous polyps (growths that protrude from a mucous membrane). [NIH] Polysaccharide: A type of carbohydrate. It contains sugar molecules that are linked together chemically. [NIH] 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] 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] Potassium: An element that is in the alkali group of metals. It has an atomic symbol K, atomic number 19, and atomic weight 39.10. It is the chief cation in the intracellular fluid of muscle and other cells. Potassium ion is a strong electrolyte and it plays a significant role in the regulation of fluid volume and maintenance of the water-electrolyte balance. [NIH] Potentiate: A degree of synergism which causes the exposure of the organism to a harmful substance to worsen a disease already contracted. [NIH] Potentiation: An overall effect of two drugs taken together which is greater than the sum of the effects of each drug taken alone. [NIH] Practicability: A non-standard characteristic of an analytical procedure. It is dependent on the scope of the method and is determined by requirements such as sample throughout and costs. [NIH] Practice Guidelines: Directions or principles presenting current or future rules of policy for the health care practitioner to assist him in patient care decisions regarding diagnosis, therapy, or related clinical circumstances. The guidelines may be developed by government agencies at any level, institutions, professional societies, governing boards, or by the convening of expert panels. The guidelines form a basis for the evaluation of all aspects of health care and delivery. [NIH] 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] Pre-Eclampsia: Development of hypertension with proteinuria, edema, or both, due to pregnancy or the influence of a recent pregnancy. It occurs after the 20th week of gestation, but it may develop before this time in the presence of trophoblastic disease. [NIH] Premalignant: A term used to describe a condition that may (or is likely to) become cancer. Also called precancerous. [NIH]
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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] Preventive Medicine: A medical specialty primarily concerned with prevention of disease and the promotion and preservation of health in the individual. [NIH] Prickle: Several layers of the epidermis where the individual cells are connected by cell bridges. [NIH] Primary tumor: The original tumor. [NIH] Primitive neuroectodermal tumors: PNET. A type of bone cancer that forms in the middle (shaft) of large bones. Also called Ewing's sarcoma/primitive neuroectodermal tumor. [NIH] Probe: An instrument used in exploring cavities, or in the detection and dilatation of strictures, or in demonstrating the potency of channels; an elongated instrument for exploring or sounding body cavities. [NIH] Prodrug: A substance that gives rise to a pharmacologically active metabolite, although not itself active (i. e. an inactive precursor). [NIH] Progeny: The offspring produced in any generation. [NIH] Progesterone: Pregn-4-ene-3,20-dione. The principal progestational hormone of the body, secreted by the corpus luteum, adrenal cortex, and placenta. Its chief function is to prepare the uterus for the reception and development of the fertilized ovum. It acts as an antiovulatory agent when administered on days 5-25 of the menstrual cycle. [NIH] Prognostic factor: A situation or condition, or a characteristic of a patient, that can be used to estimate the chance of recovery from a disease, or the chance of the disease recurring (coming back). [NIH] Progression: Increase in the size of a tumor or spread of cancer in the body. [NIH] Progressive: Advancing; going forward; going from bad to worse; increasing in scope or severity. [EU] Projection: A defense mechanism, operating unconsciously, whereby that which is emotionally unacceptable in the self is rejected and attributed (projected) to others. [NIH] Proline: A non-essential amino acid that is synthesized from glutamic acid. It is an essential component of collagen and is important for proper functioning of joints and tendons. [NIH] Promoter: A chemical substance that increases the activity of a carcinogenic process. [NIH] 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] Promyelocytic leukemia: A type of acute myeloid leukemia, a quickly progressing disease in which too many immature blood-forming cells are found in the blood and bone marrow. [NIH]
Prophase: The first phase of cell division, in which the chromosomes become visible, the nucleus starts to lose its identity, the spindle appears, and the centrioles migrate toward opposite poles. [NIH] Prophylaxis: An attempt to prevent disease. [NIH] Proportional: Being in proportion : corresponding in size, degree, or intensity, having the same or a constant ratio; of, relating to, or used in determining proportions. [EU] Prospective study: An epidemiologic study in which a group of individuals (a cohort), all free of a particular disease and varying in their exposure to a possible risk factor, is followed over a specific amount of time to determine the incidence rates of the disease in the exposed
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and unexposed groups. [NIH] Prostaglandin: Any of a group of components derived from unsaturated 20-carbon fatty acids, primarily arachidonic acid, via the cyclooxygenase pathway that are extremely potent mediators of a diverse group of physiologic processes. The abbreviation for prostaglandin is PG; specific compounds are designated by adding one of the letters A through I to indicate the type of substituents found on the hydrocarbon skeleton and a subscript (1, 2 or 3) to indicate the number of double bonds in the hydrocarbon skeleton e.g., PGE2. The predominant naturally occurring prostaglandins all have two double bonds and are synthesized from arachidonic acid (5,8,11,14-eicosatetraenoic acid) by the pathway shown in the illustration. The 1 series and 3 series are produced by the same pathway with fatty acids having one fewer double bond (8,11,14-eicosatrienoic acid or one more double bond (5,8,11,14,17-eicosapentaenoic acid) than arachidonic acid. The subscript a or ß indicates the configuration at C-9 (a denotes a substituent below the plane of the ring, ß, above the plane). The naturally occurring PGF's have the a configuration, e.g., PGF2a. All of the prostaglandins act by binding to specific cell-surface receptors causing an increase in the level of the intracellular second messenger cyclic AMP (and in some cases cyclic GMP also). The effect produced by the cyclic AMP increase depends on the specific cell type. In some cases there is also a positive feedback effect. Increased cyclic AMP increases prostaglandin synthesis leading to further increases in cyclic AMP. [EU] Prostaglandins A: (13E,15S)-15-Hydroxy-9-oxoprosta-10,13-dien-1-oic acid (PGA(1)); (5Z,13E,15S)-15-hydroxy-9-oxoprosta-5,10,13-trien-1-oic acid (PGA(2)); (5Z,13E,15S,17Z)-15hydroxy-9-oxoprosta-5,10,13,17-tetraen-1-oic acid (PGA(3)). A group of naturally occurring secondary prostaglandins derived from PGE. PGA(1) and PGA(2) as well as their 19hydroxy derivatives are found in many organs and tissues. [NIH] Prostate: A gland in males that surrounds the neck of the bladder and the urethra. It secretes a substance that liquifies coagulated semen. It is situated in the pelvic cavity behind the lower part of the pubic symphysis, above the deep layer of the triangular ligament, and rests upon the rectum. [NIH] Prostatic Intraepithelial Neoplasia: A premalignant change arising in the prostatic epithelium, regarded as the most important and most likely precursor of prostatic adenocarcinoma. The neoplasia takes the form of an intra-acinar or ductal proliferation of secretory cells with unequivocal nuclear anaplasia, which corresponds to nuclear grade 2 and 3 invasive prostate cancer. [NIH] Protease: Proteinase (= any enzyme that catalyses the splitting of interior peptide bonds in a protein). [EU] Protective Devices: Devices designed to provide personal protection against injury to individuals exposed to hazards in industry, sports, aviation, or daily activities. [NIH] Protein C: A vitamin-K dependent zymogen present in the blood, which, upon activation by thrombin and thrombomodulin exerts anticoagulant properties by inactivating factors Va and VIIIa at the rate-limiting steps of thrombin formation. [NIH] Protein Conformation: The characteristic 3-dimensional shape of a protein, including the secondary, supersecondary (motifs), tertiary (domains) and quaternary structure of the peptide chain. Quaternary protein structure describes the conformation assumed by multimeric proteins (aggregates of more than one polypeptide chain). [NIH] Protein 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
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recurrent venous and arterial thrombosis. [NIH] Protein Subunits: Single chains of amino acids that are the units of a multimeric protein. They can be identical or non-identical subunits. [NIH] Proteins: Polymers of amino acids linked by peptide bonds. The specific sequence of amino acids determines the shape and function of the protein. [NIH] Proteinuria: The presence of protein in the urine, indicating that the kidneys are not working properly. [NIH] Proteolytic: 1. Pertaining to, characterized by, or promoting proteolysis. 2. An enzyme that promotes proteolysis (= the splitting of proteins by hydrolysis of the peptide bonds with formation of smaller polypeptides). [EU] Protons: Stable elementary particles having the smallest known positive charge, found in the nuclei of all elements. The proton mass is less than that of a neutron. A proton is the nucleus of the light hydrogen atom, i.e., the hydrogen ion. [NIH] 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] Protozoal: Having to do with the simplest organisms in the animal kingdom. Protozoa are single-cell organisms, such as ameba, and are different from bacteria, which are not members of the animal kingdom. Some protozoa can be seen without a microscope. [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] Psoriasis: A common genetically determined, chronic, inflammatory skin disease characterized by rounded erythematous, dry, scaling patches. The lesions have a predilection for nails, scalp, genitalia, extensor surfaces, and the lumbosacral region. Accelerated epidermopoiesis is considered to be the fundamental pathologic feature in psoriasis. [NIH] 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] Public Health: Branch of medicine concerned with the prevention and control of disease and disability, and the promotion of physical and mental health of the population on the international, national, state, or municipal level. [NIH] Public Policy: A course or method of action selected, usually by a government, from among alternatives to guide and determine present and future decisions. [NIH] Publishing: "The business or profession of the commercial production and issuance of
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literature" (Webster's 3d). It includes the publisher, publication processes, editing and editors. Production may be by conventional printing methods or by electronic publishing. [NIH]
Pulmonary: Relating to the lungs. [NIH] Pulmonary Artery: The short wide vessel arising from the conus arteriosus of the right ventricle and conveying unaerated blood to the lungs. [NIH] Pulmonary Edema: An accumulation of an excessive amount of watery fluid in the lungs, may be caused by acute exposure to dangerous concentrations of irritant gasses. [NIH] Pulmonary Ventilation: The total volume of gas per minute inspired or expired measured in liters per minute. [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] Purifying: Respiratory equipment whose function is to remove contaminants from otherwise wholesome air. [NIH] Purines: A series of heterocyclic compounds that are variously substituted in nature and are known also as purine bases. They include adenine and guanine, constituents of nucleic acids, as well as many alkaloids such as caffeine and theophylline. Uric acid is the metabolic end product of purine metabolism. [NIH] Purpura: Purplish or brownish red discoloration, easily visible through the epidermis, caused by hemorrhage into the tissues. [NIH] Purulent: Consisting of or containing pus; associated with the formation of or caused by pus. [EU] Pustular: Pertaining to or of the nature of a pustule; consisting of pustules (= a visible collection of pus within or beneath the epidermis). [EU] Pyruvate Dehydrogenase Complex: An organized assembly of three kinds of enzymes; catalyzes the oxidative decarboxylation of pyruvate. [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] Quercetin: Aglucon of quercetrin, rutin, and other glycosides. It is widely distributed in the plant kingdom, especially in rinds and barks, clover blossoms, and ragweed pollen. [NIH] Quiescent: Marked by a state of inactivity or repose. [EU] Quinone Reductases: NAD(P)H:(quinone acceptor) oxidoreductases. A family that includes three enzymes which are distinguished by their sensitivity to various inhibitors. EC 1.6.99.2 (NAD(P)H dehydrogenase (quinone)) is a flavoprotein which reduces various quinones in the presence of NADH or NADPH and is inhibited by dicoumarol. EC 1.6.99.5 (NADH dehydrogenase (quinone)) requires NADH, is inhibited by AMP and 2,4-dinitrophenol but not by dicoumarol or folic acid derivatives. EC 1.6.99.6 (NADPH dehydrogenase (quinone)) requires NADPH and is inhibited by dicoumarol and folic acid derivatives but not by 2,4dinitrophenol. [NIH] Quinones: Hydrocarbon rings which contain two ketone moieties in any position. They can be substituted in any position except at the ketone groups. [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]
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Race: A population within a species which exhibits general similarities within itself, but is both discontinuous and distinct from other populations of that species, though not sufficiently so as to achieve the status of a taxon. [NIH] Radiation: Emission or propagation of electromagnetic energy (waves/rays), or the waves/rays themselves; a stream of electromagnetic particles (electrons, neutrons, protons, alpha particles) or a mixture of these. The most common source is the sun. [NIH] Radiation 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] Radiolabeled: Any compound that has been joined with a radioactive substance. [NIH] Radiopharmaceutical: Any medicinal product which, when ready for use, contains one or more radionuclides (radioactive isotopes) included for a medicinal purpose. [NIH] Radiotherapy: The use of ionizing radiation to treat malignant neoplasms and other benign conditions. The most common forms of ionizing radiation used as therapy are x-rays, gamma rays, and electrons. A special form of radiotherapy, targeted radiotherapy, links a cytotoxic radionuclide to a molecule that targets the tumor. When this molecule is an antibody or other immunologic molecule, the technique is called radioimmunotherapy. [NIH] 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] Reactive Oxygen Species: Reactive intermediate oxygen species including both radicals and non-radicals. These substances are constantly formed in the human body and have been shown to kill bacteria and inactivate proteins, and have been implicated in a number of diseases. Scientific data exist that link the reactive oxygen species produced by inflammatory phagocytes to cancer development. [NIH] Reagent: A substance employed to produce a chemical reaction so as to detect, measure, produce, etc., other substances. [EU] Receptor: A molecule inside or on the surface of a cell that binds to a specific substance and causes a specific physiologic effect in the cell. [NIH] Recombinant: A cell or an individual with a new combination of genes not found together in either parent; usually applied to linked genes. [EU] Recombinant Fusion Proteins: Proteins that are the result of genetic engineering. A regulatory part or promoter of one or more genes is combined with a structural gene. The fusion protein is formed after transcription and translation of the fused gene. This type of fusion protein is used in the study of gene regulation or structure-activity relationships. They might also be used clinically as targeted toxins (immunotoxins). [NIH] Recombinant Proteins: Proteins prepared by recombinant DNA technology. [NIH] Recombination: The formation of new combinations of genes as a result of segregation in crosses between genetically different parents; also the rearrangement of linked genes due to crossing-over. [NIH] Rectum: The last 8 to 10 inches of the large intestine. [NIH]
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Recur: To occur again. Recurrence is the return of cancer, at the same site as the original (primary) tumor or in another location, after the tumor had disappeared. [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] 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] Regression Analysis: Procedures for finding the mathematical function which best describes the relationship between a dependent variable and one or more independent variables. In linear regression (see linear models) the relationship is constrained to be a straight line and least-squares analysis is used to determine the best fit. In logistic regression (see logistic models) the dependent variable is qualitative rather than continuously variable and likelihood functions are used to find the best relationship. In multiple regression the dependent variable is considered to depend on more than a single independent variable. [NIH]
Regulon: In eukaryotes, a genetic unit consisting of a noncontiguous group of genes under the control of a single regulator gene. In bacteria, regulons are global regulatory systems involved in the interplay of pleiotropic regulatory domains. These regulatory systems consist of several operons. [NIH] Relapse: The return of signs and symptoms of cancer after a period of improvement. [NIH] Relaxant: 1. Lessening or reducing tension. 2. An agent that lessens tension. [EU] 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 Artery: A branch of the abdominal aorta which supplies the kidneys, adrenal glands and ureters. [NIH] Renal cell cancer: Cancer that develops in the lining of the renal tubules, which filter the blood and produce urine. [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
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most powerful directly pressor substance known. It causes contraction of the arteriolar smooth muscle and has other indirect actions mediated through the adrenal cortex. [NIH] Reperfusion: Restoration of blood supply to tissue which is ischemic due to decrease in normal blood supply. The decrease may result from any source including atherosclerotic obstruction, narrowing of the artery, or surgical clamping. It is primarily a procedure for treating infarction or other ischemia, by enabling viable ischemic tissue to recover, thus limiting further necrosis. However, it is thought that reperfusion can itself further damage the ischemic tissue, causing reperfusion injury. [NIH] Reperfusion Injury: Functional, metabolic, or structural changes, including necrosis, in ischemic tissues thought to result from reperfusion to ischemic areas of the tissue. The most common instance is myocardial reperfusion injury. [NIH] Reproductive cells: Egg and sperm cells. Each mature reproductive cell carries a single set of 23 chromosomes. [NIH] Reproductive system: In women, this system includes the ovaries, the fallopian tubes, the uterus (womb), the cervix, and the vagina (birth canal). The reproductive system in men includes the prostate, the testes, and the penis. [NIH] Reserpine: An alkaloid found in the roots of Rauwolfia serpentina and R. vomitoria. Reserpine inhibits the uptake of norepinephrine into storage vesicles resulting in depletion of catecholamines and serotonin from central and peripheral axon terminals. It has been used as an antihypertensive and an antipsychotic as well as a research tool, but its adverse effects limit its clinical use. [NIH] 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 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]
Restoration: Broad term applied to any inlay, crown, bridge or complete denture which restores or replaces loss of teeth or oral tissues. [NIH] Resuscitation: The restoration to life or consciousness of one apparently dead; it includes such measures as artificial respiration and cardiac massage. [EU] 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,
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all-trans retinal (trans-r.); visual yellow; xanthopsin) results from the bleaching of rhodopsin by light, in which the 11-cis form is converted to the all-trans form. Retinal also combines with opsins in the cones (photopsins) to form the three pigments responsible for colour vision. Called also retinal, and retinene1. [EU] Retinal Ganglion Cells: Cells of the innermost nuclear layer of the retina, the ganglion cell layer, which project axons through the optic nerve to the brain. They are quite variable in size and in the shapes of their dendritic arbors, which are generally confined to the inner plexiform layer. [NIH] Retinal pigment epithelium: The pigment cell layer that nourishes the retinal cells; located just outside the retina and attached to the choroid. [NIH] Retinoblastoma: An eye cancer that most often occurs in children younger than 5 years. It occurs in hereditary and nonhereditary (sporadic) forms. [NIH] Retinoid: Vitamin A or a vitamin A-like compound. [NIH] Retinol: Vitamin A. It is essential for proper vision and healthy skin and mucous membranes. Retinol is being studied for cancer prevention; it belongs to the family of drugs called retinoids. [NIH] Retrospective: Looking back at events that have already taken place. [NIH] Retrovirus: A member of a group of RNA viruses, the RNA of which is copied during viral replication into DNA by reverse transcriptase. The viral DNA is then able to be integrated into the host chromosomal DNA. [NIH] Reversion: A return to the original condition, e. g. the reappearance of the normal or wild type in previously mutated cells, tissues, or organisms. [NIH] Rheumatic Heart Disease: Disease of the heart resulting from rheumatic fever and characterized by inflammatory changes in the myocardium or scarring of the valves. [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] Ribose: A pentose active in biological systems usually in its D-form. [NIH] Ribosome: A granule of protein and RNA, synthesized in the nucleolus and found in the cytoplasm of cells. Ribosomes are the main sites of protein synthesis. Messenger RNA attaches to them and there receives molecules of transfer RNA bearing amino acids. [NIH] Rigidity: Stiffness or inflexibility, chiefly that which is abnormal or morbid; rigor. [EU] Risk factor: A habit, trait, condition, or genetic alteration that increases a person's chance of developing a disease. [NIH] Rod: A reception for vision, located in the retina. [NIH] Rotenone: A botanical insecticide that is an inhibitor of mitochondrial electron transport. [NIH]
Rutin: 3-((6-O-(6-Deoxy-alpha-L-mannopyranosyl)-beta-D-glucopyranosyl)oxy)-2-(3,4dihydroxyphenyl)-5,7-dihydroxy-4H-1-benzopyran-4-one. Found in many plants, including buckwheat, tobacco, forsythia, hydrangea, pansies, etc. It has been used therapeutically to decrease capillary fragility. [NIH] Salicylate: Non-steroidal anti-inflammatory drugs. [NIH]
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Salicylic: A tuberculosis drug. [NIH] Salicylic Acids: Derivatives and salts of salicylic acid. [NIH] Saliva: The clear, viscous fluid secreted by the salivary glands and mucous glands of the mouth. It contains mucins, water, organic salts, and ptylin. [NIH] Salivary: The duct that convey saliva to the mouth. [NIH] Salivary glands: Glands in the mouth that produce saliva. [NIH] Salpingitis: 1. Inflammation of the uterine tube. 2. Inflammation of the auditory tube. [EU] Saponins: Sapogenin glycosides. A type of glycoside widely distributed in plants. Each consists of a sapogenin as the aglycon moiety, and a sugar. The sapogenin may be a steroid or a triterpene and the sugar may be glucose, galactose, a pentose, or a methylpentose. Sapogenins are poisonous towards the lower forms of life and are powerful hemolytics when injected into the blood stream able to dissolve red blood cells at even extreme dilutions. [NIH] Sarcoidosis: An idiopathic systemic inflammatory granulomatous disorder comprised of epithelioid and multinucleated giant cells with little necrosis. It usually invades the lungs with fibrosis and may also involve lymph nodes, skin, liver, spleen, eyes, phalangeal bones, and parotid glands. [NIH] Sarcoma: A connective tissue neoplasm formed by proliferation of mesodermal cells; it is usually highly malignant. [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] Sclera: The tough white outer coat of the eyeball, covering approximately the posterior fivesixths of its surface, and continuous anteriorly with the cornea and posteriorly with the external sheath of the optic nerve. [EU] Sclerosis: A pathological process consisting of hardening or fibrosis of an anatomical structure, often a vessel or a nerve. [NIH] Screening: Checking for disease when there are no symptoms. [NIH] Sebum: The oily substance secreted by sebaceous glands. It is composed of keratin, fat, and cellular debris. [NIH] Second Messenger Systems: Systems in which an intracellular signal is generated in response to an intercellular primary messenger such as a hormone or neurotransmitter. They are intermediate signals in cellular processes such as metabolism, secretion, contraction, phototransduction, and cell growth. Examples of second messenger systems are the adenyl cyclase-cyclic AMP system, the phosphatidylinositol diphosphate-inositol triphosphate system, and the cyclic GMP system. [NIH] Secondary tumor: Cancer that has spread from the organ in which it first appeared to another organ. For example, breast cancer cells may spread (metastasize) to the lungs and cause the growth of a new tumor. When this happens, the disease is called metastatic breast cancer, and the tumor in the lungs is called a secondary tumor. Also called secondary
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cancer. [NIH] Secretin: A hormone made in the duodenum. Causes the stomach to make pepsin, the liver to make bile, and the pancreas to make a digestive juice. [NIH] Secretion: 1. The process of elaborating a specific product as a result of the activity of a gland; this activity may range from separating a specific substance of the blood to the elaboration of a new chemical substance. 2. Any substance produced by secretion. [EU] Secretory: Secreting; relating to or influencing secretion or the secretions. [NIH] Sedative: 1. Allaying activity and excitement. 2. An agent that allays excitement. [EU] Segregation: The separation in meiotic cell division of homologous chromosome pairs and their contained allelomorphic gene pairs. [NIH] 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] 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] Selenocysteine: A naturally occurring amino acid in both eukaryotic and prokaryotic organisms. It is found in tRNAs and in the catalytic site of some enzymes. The genes for glutathione peroxidase and formate dehydrogenase contain the TGA codon, which codes for this amino acid. [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] Seminiferous tubule: Tube used to transport sperm made in the testes. [NIH] Semisynthetic: Produced by chemical manipulation of naturally occurring substances. [EU] Senescence: The bodily and mental state associated with advancing age. [NIH] Senile: Relating or belonging to old age; characteristic of old age; resulting from infirmity of old age. [NIH] Sepsis: The presence of bacteria in the bloodstream. [NIH] Septic: Produced by or due to decomposition by microorganisms; putrefactive. [EU] Sequence Homology: The degree of similarity between sequences. Studies of amino acid and nucleotide sequences provide useful information about the genetic relatedness of certain species. [NIH] Sequencing: The determination of the order of nucleotides in a DNA or RNA chain. [NIH] Serologic: Analysis of a person's serum, especially specific immune or lytic serums. [NIH] Serotonin: A biochemical messenger and regulator, synthesized from the essential amino acid L-tryptophan. In humans it is found primarily in the central nervous system, gastrointestinal tract, and blood platelets. Serotonin mediates several important physiological functions including neurotransmission, gastrointestinal motility, hemostasis, and cardiovascular integrity. Multiple receptor families (receptors, serotonin) explain the broad physiological actions and distribution of this biochemical mediator. [NIH]
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Serous: Having to do with serum, the clear liquid part of blood. [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] Serrated: Having notches or teeth on the edge as a saw has. [NIH] Serum: The clear liquid part of the blood that remains after blood cells and clotting proteins have been removed. [NIH] 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] Shock: The general bodily disturbance following a severe injury; an emotional or moral upset occasioned by some disturbing or unexpected experience; disruption of the circulation, which can upset all body functions: sometimes referred to as circulatory shock. [NIH]
Side effect: A consequence other than the one(s) for which an agent or measure is used, as the adverse effects produced by a drug, especially on a tissue or organ system other than the one sought to be benefited by its administration. [EU] Signal Transduction: The intercellular or intracellular transfer of information (biological activation/inhibition) through a signal pathway. In each signal transduction system, an activation/inhibition signal from a biologically active molecule (hormone, neurotransmitter) is mediated via the coupling of a receptor/enzyme to a second messenger system or to an ion channel. Signal transduction plays an important role in activating cellular functions, cell differentiation, and cell proliferation. Examples of signal transduction systems are the GABA-postsynaptic receptor-calcium ion channel system, the receptor-mediated T-cell activation pathway, and the receptor-mediated activation of phospholipases. Those coupled to membrane depolarization or intracellular release of calcium include the receptormediated activation of cytotoxic functions in granulocytes and the synaptic potentiation of protein kinase activation. Some signal transduction pathways may be part of larger signal transduction pathways; for example, protein kinase activation is part of the platelet activation signal pathway. [NIH] Signs and Symptoms: Clinical manifestations that can be either objective when observed by a physician, or subjective when perceived by the patient. [NIH] Silicon: A trace element that constitutes about 27.6% of the earth's crust in the form of silicon dioxide. It does not occur free in nature. Silicon has the atomic symbol Si, atomic number 14, and atomic weight 28.09. [NIH] Silicon Dioxide: Silica. Transparent, tasteless crystals found in nature as agate, amethyst, chalcedony, cristobalite, flint, sand, quartz, and tridymite. The compound is insoluble in water or acids except hydrofluoric acid. [NIH] Silicosis: A type of pneumoconiosis caused by inhalation of particles of silica, quartz, ganister or slate. [NIH] Silymarin: A mixture of flavonoids extracted from seeds of the milk thistle, Silybum marianum. It consists primarily of three isomers: silicristin, silidianin, and silybin, its major component. Silymarin displays antioxidant and membrane stabilizing activity. It protects
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various tissues and organs against chemical injury, and shows potential as an antihepatoxic agent. [NIH] Skeletal: Having to do with the skeleton (boney part of the body). [NIH] Skeleton: The framework that supports the soft tissues of vertebrate animals and protects many of their internal organs. The skeletons of vertebrates are made of bone and/or cartilage. [NIH] Skin Aging: The process of aging due to changes in the structure and elasticity of the skin over time. It may be a part of physiological aging or it may be due to the effects of ultraviolet radiation, usually through exposure to sunlight. [NIH] Skull: The skeleton of the head including the bones of the face and the bones enclosing the brain. [NIH] Small cell lung cancer: A type of lung cancer in which the cells appear small and round when viewed under the microscope. Also called oat cell lung cancer. [NIH] Small intestine: The part of the digestive tract that is located between the stomach and the large intestine. [NIH] Smooth muscle: Muscle that performs automatic tasks, such as constricting blood vessels. [NIH]
Sneezing: Sudden, forceful, involuntary expulsion of air from the nose and mouth caused by irritation to the mucous membranes of the upper respiratory tract. [NIH] Soaps: Sodium or potassium salts of long chain fatty acids. These detergent substances are obtained by boiling natural oils or fats with caustic alkali. Sodium soaps are harder and are used as topical anti-infectives and vehicles in pills and liniments; potassium soaps are soft, used as vehicles for ointments and also as topical antimicrobials. [NIH] Sodium: An element that is a member of the alkali group of metals. It has the atomic symbol Na, atomic number 11, and atomic weight 23. With a valence of 1, it has a strong affinity for oxygen and other nonmetallic elements. Sodium provides the chief cation of the extracellular body fluids. Its salts are the most widely used in medicine. (From Dorland, 27th ed) Physiologically the sodium ion plays a major role in blood pressure regulation, maintenance of fluid volume, and electrolyte balance. [NIH] Soft tissue: Refers to muscle, fat, fibrous tissue, blood vessels, or other supporting tissue of the body. [NIH] 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] Sorbitol: A polyhydric alcohol with about half the sweetness of sucrose. Sorbitol occurs naturally and is also produced synthetically from glucose. It was formerly used as a diuretic and may still be used as a laxative and in irrigating solutions for some surgical procedures. It is also used in many manufacturing processes, as a pharmaceutical aid, and in several research applications. [NIH]
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Spasm: An involuntary contraction of a muscle or group of muscles. Spasms may involve skeletal muscle or smooth muscle. [NIH] Spasmodic: Of the nature of a spasm. [EU] Spatial disorientation: Loss of orientation in space where person does not know which way is up. [NIH] Specialist: In medicine, one who concentrates on 1 special branch of medical science. [NIH] Species: A taxonomic category subordinate to a genus (or subgenus) and superior to a subspecies or variety, composed of individuals possessing common characters distinguishing them from other categories of individuals of the same taxonomic level. In taxonomic nomenclature, species are designated by the genus name followed by a Latin or Latinized adjective or noun. [EU] Specificity: Degree of selectivity shown by an antibody with respect to the number and types of antigens with which the antibody combines, as well as with respect to the rates and the extents of these reactions. [NIH] Spectrophotometry: The art or process of comparing photometrically the relative intensities of the light in different parts of the spectrum. [NIH] Spectrum: A charted band of wavelengths of electromagnetic vibrations obtained by refraction and diffraction. By extension, a measurable range of activity, such as the range of bacteria affected by an antibiotic (antibacterial s.) or the complete range of manifestations of a disease. [EU] Sperm: The fecundating fluid of the male. [NIH] Spermatozoa: Mature male germ cells that develop in the seminiferous tubules of the testes. Each consists of a head, a body, and a tail that provides propulsion. The head consists mainly of chromatin. [NIH] Spinal cord: The main trunk or bundle of nerves running down the spine through holes in the spinal bone (the vertebrae) from the brain to the level of the lower back. [NIH] 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] Spores: The reproductive elements of lower organisms, such as protozoa, fungi, and cryptogamic plants. [NIH] Squamous: Scaly, or platelike. [EU] Squamous cell carcinoma: Cancer that begins in squamous cells, which are thin, flat cells resembling fish scales. Squamous cells are found in the tissue that forms the surface of the skin, the lining of the hollow organs of the body, and the passages of the respiratory and digestive tracts. Also called epidermoid carcinoma. [NIH] Squamous cell carcinoma: Cancer that begins in squamous cells, which are thin, flat cells resembling fish scales. Squamous cells are found in the tissue that forms the surface of the skin, the lining of the hollow organs of the body, and the passages of the respiratory and digestive tracts. Also called epidermoid carcinoma. [NIH] Squamous cells: Flat cells that look like fish scales under a microscope. These cells cover internal and external surfaces of the body. [NIH] Stabilizer: A device for maintaining constant X-ray tube voltage or current. [NIH]
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Staurosporine: A drug that belongs to the family of drugs called alkaloids. It is being studied in the treatment of cancer. [NIH] Steady state: Dynamic equilibrium. [EU] 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 Cells: Relatively undifferentiated cells of the same lineage (family type) that retain the ability to divide and cycle throughout postnatal life to provide cells that can become specialized and take the place of those that die or are lost. [NIH] Sterile: Unable to produce children. [NIH] Sterility: 1. The inability to produce offspring, i.e., the inability to conceive (female s.) or to induce conception (male s.). 2. The state of being aseptic, or free from microorganisms. [EU] 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] Strand: DNA normally exists in the bacterial nucleus in a helix, in which two strands are coiled together. [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] Stria: 1. A streak, or line. 2. A narrow bandlike structure; a general term for such longitudinal collections of nerve fibres in the brain. [EU] Stria Vascularis: A layer of highly vascular pigmented granular cells on the outer wall of the cochlear duct. [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] 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] Structure-Activity Relationship: The relationship between the chemical structure of a compound and its biological or pharmacological activity. Compounds are often classed together because they have structural characteristics in common including shape, size, stereochemical arrangement, and distribution of functional groups. Other factors contributing to structure-activity relationship include chemical reactivity, electronic effects, resonance, and inductive effects. [NIH]
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Styrene: A colorless, toxic liquid with a strong aromatic odor. It is used to make rubbers, polymers and copolymers, and polystyrene plastics. [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] Submaxillary: Four to six lymph glands, located between the lower jaw and the submandibular salivary gland. [NIH] Subspecies: A category intermediate in rank between species and variety, based on a smaller number of correlated characters than are used to differentiate species and generally conditioned by geographical and/or ecological occurrence. [NIH] Substance P: An eleven-amino acid neurotransmitter that appears in both the central and peripheral nervous systems. It is involved in transmission of pain, causes rapid contractions of the gastrointestinal smooth muscle, and modulates inflammatory and immune responses. [NIH]
Substrate: A substance upon which an enzyme acts. [EU] Substrate Specificity: A characteristic feature of enzyme activity in relation to the kind of substrate on which the enzyme or catalytic molecule reacts. [NIH] 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] Sunburn: An injury to the skin causing erythema, tenderness, and sometimes blistering and resulting from excessive exposure to the sun. The reaction is produced by the ultraviolet radiation in sunlight. [NIH] Superoxide: Derivative of molecular oxygen that can damage cells. [NIH] Superoxide Dismutase: An oxidoreductase that catalyzes the reaction between superoxide anions and hydrogen to yield molecular oxygen and hydrogen peroxide. The enzyme protects the cell against dangerous levels of superoxide. EC 1.15.1.1. [NIH] Supplementation: Adding nutrients to the diet. [NIH] Supportive care: Treatment given to prevent, control, or relieve complications and side effects and to improve the comfort and quality of life of people who have cancer. [NIH] 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] Suppurative: Consisting of, containing, associated with, or identified by the formation of pus. [NIH] Suramin: A polyanionic compound with an unknown mechanism of action. It is used parenterally in the treatment of African trypanosomiasis and it has been used clinically with diethylcarbamazine to kill the adult Onchocerca. (From AMA Drug Evaluations Annual, 1992, p1643) It has also been shown to have potent antineoplastic properties. [NIH] Surface Plasmon Resonance: A biosensing technique in which biomolecules capable of
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binding to specific analytes or ligands are first immobilized on one side of a metallic film. Light is then focused on the opposite side of the film to excite the surface plasmons, that is, the oscillations of free electrons propagating along the film's surface. The refractive index of light reflecting off this surface is measured. When the immobilized biomolecules are bound by their ligands, an alteration in surface plasmons on the opposite side of the film is created which is directly proportional to the change in bound, or adsorbed, mass. Binding is measured by changes in the refractive index. The technique is used to study biomolecular interactions, such as antigen-antibody binding. [NIH] Surfactant: A fat-containing protein in the respiratory passages which reduces the surface tension of pulmonary fluids and contributes to the elastic properties of pulmonary tissue. [NIH]
Survival Analysis: A class of statistical procedures for estimating the survival function (function of time, starting with a population 100% well at a given time and providing the percentage of the population still well at later times). The survival analysis is then used for making inferences about the effects of treatments, prognostic factors, exposures, and other covariates on the function. [NIH] Survival Rate: The proportion of survivors in a group, e.g., of patients, studied and followed over a period, or the proportion of persons in a specified group alive at the beginning of a time interval who survive to the end of the interval. It is often studied using life table methods. [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] Sympathomimetic: 1. Mimicking the effects of impulses conveyed by adrenergic postganglionic fibres of the sympathetic nervous system. 2. An agent that produces effects similar to those of impulses conveyed by adrenergic postganglionic fibres of the sympathetic nervous system. Called also adrenergic. [EU] Symphysis: A secondary cartilaginous joint. [NIH] Symptomatic: Having to do with symptoms, which are signs of a condition or disease. [NIH] Synapses: Specialized junctions at which a neuron communicates with a target cell. At classical synapses, a neuron's presynaptic terminal releases a chemical transmitter stored in synaptic vesicles which diffuses across a narrow synaptic cleft and activates receptors on the postsynaptic membrane of the target cell. The target may be a dendrite, cell body, or axon of another neuron, or a specialized region of a muscle or secretory cell. Neurons may also communicate through direct electrical connections which are sometimes called electrical synapses; these are not included here but rather in gap junctions. [NIH] Synapsis: The pairing between homologous chromosomes of maternal and paternal origin during the prophase of meiosis, leading to the formation of gametes. [NIH] Synaptic: Pertaining to or affecting a synapse (= site of functional apposition between neurons, at which an impulse is transmitted from one neuron to another by electrical or chemical means); pertaining to synapsis (= pairing off in point-for-point association of homologous chromosomes from the male and female pronuclei during the early prophase of meiosis). [EU] Synaptic Membranes: Cell membranes associated with synapses. Both presynaptic and postsynaptic membranes are included along with their integral or tightly associated specializations for the release or reception of transmitters. [NIH] Synaptic Transmission: The communication from a neuron to a target (neuron, muscle, or secretory cell) across a synapse. In chemical synaptic transmission, the presynaptic neuron
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releases a neurotransmitter that diffuses across the synaptic cleft and binds to specific synaptic receptors. These activated receptors modulate ion channels and/or secondmessenger systems to influence the postsynaptic cell. Electrical transmission is less common in the nervous system, and, as in other tissues, is mediated by gap junctions. [NIH] Synergistic: Acting together; enhancing the effect of another force or agent. [EU] Synovial: Of pertaining to, or secreting synovia. [EU] Synovial Fluid: The clear, viscous fluid secreted by the synovial membrane. It contains mucin, albumin, fat, and mineral salts and serves to lubricate joints. [NIH] Synovial Membrane: The inner membrane of a joint capsule surrounding a freely movable joint. It is loosely attached to the external fibrous capsule and secretes synovial fluid. [NIH] Systemic: Affecting the entire body. [NIH] Systemic lupus erythematosus: SLE. A chronic inflammatory connective tissue disease marked by skin rashes, joint pain and swelling, inflammation of the kidneys, inflammation of the fibrous tissue surrounding the heart (i.e., the pericardium), as well as other problems. Not all affected individuals display all of these problems. May be referred to as lupus. [NIH] Systolic: Indicating the maximum arterial pressure during contraction of the left ventricle of the heart. [EU] Systolic heart failure: Inability of the heart to contract with enough force to pump adequate amounts of blood through the body. [NIH] Taurine: 2-Aminoethanesulfonic acid. A conditionally essential nutrient, important during mammalian development. It is present in milk but is isolated mostly from ox bile and strongly conjugates bile acids. [NIH] Technology Transfer: Spread and adoption of inventions and techniques from one geographic area to another, from one discipline to another, or from one sector of the economy to another. For example, improvements in medical equipment may be transferred from industrial countries to developing countries, advances arising from aerospace engineering may be applied to equipment for persons with disabilities, and innovations in science arising from government research are made available to private enterprise. [NIH] Telangiectasia: The permanent enlargement of blood vessels, causing redness in the skin or mucous membranes. [NIH] Telencephalon: Paired anteriolateral evaginations of the prosencephalon plus the lamina terminalis. The cerebral hemispheres are derived from it. Many authors consider cerebrum a synonymous term to telencephalon, though a minority include diencephalon as part of the cerebrum (Anthoney, 1994). [NIH] Tellurium: Tellurium. An element that is a member of the chalcogen family. It has the atomic symbol Te, atomic number 52, and atomic weight 127.60. It has been used as a coloring agent and in the manufacture of electrical equipment. Exposure may cause nausea, vomiting, and CNS depression. [NIH] Telophase: The final phase of cell division, in which two daughter nuclei are formed, the cytoplasm divides, and the chromosomes lose their distinctness and are transformed into chromatin networks. [NIH] Temporal: One of the two irregular bones forming part of the lateral surfaces and base of the skull, and containing the organs of hearing. [NIH] Tendinitis: Inflammation of tendons and of tendon-muscle attachments. [EU] Teratogenic: Tending to produce anomalies of formation, or teratism (= anomaly of formation or development : condition of a monster). [EU]
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Terminator: A DNA sequence sited at the end of a transcriptional unit that signals the end of transcription. [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] Tetany: 1. Hyperexcitability of nerves and muscles due to decrease in concentration of extracellular ionized calcium, which may be associated with such conditions as parathyroid hypofunction, vitamin D deficiency, and alkalosis or result from ingestion of alkaline salts; it is characterized by carpopedal spasm, muscular twitching and cramps, laryngospasm with inspiratory stridor, hyperreflexia and choreiform movements. 2. Tetanus. [EU] Tetracycline: An antibiotic originally produced by Streptomyces viridifaciens, but used mostly in synthetic form. It is an inhibitor of aminoacyl-tRNA binding during protein synthesis. [NIH] 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] 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] Thiobarbituric Acid Reactive Substances: Low-molecular-weight end products, probably malondialdehyde, that are formed during the decomposition of lipid peroxidation products. These compounds react with thiobarbituric acid to form a fluorescent red adduct. [NIH] Thioguanine: An antineoplastic compound which also has antimetabolite action. The drug is used in the therapy of acute leukemia. [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] Threonine: An essential amino acid occurring naturally in the L-form, which is the active form. It is found in eggs, milk, gelatin, and other proteins. [NIH] Threshold: For a specified sensory modality (e. g. light, sound, vibration), the lowest level (absolute threshold) or smallest difference (difference threshold, difference limen) or intensity of the stimulus discernible in prescribed conditions of stimulation. [NIH] Thrombin: An enzyme formed from prothrombin that converts fibrinogen to fibrin. (Dorland, 27th ed) EC 3.4.21.5. [NIH] Thrombocytes: Blood cells that help prevent bleeding by causing blood clots to form. Also called platelets. [NIH] Thrombocytopenia: A decrease in the number of blood platelets. [NIH] Thrombomodulin: A cell surface glycoprotein of endothelial cells that binds thrombin and serves as a cofactor in the activation of protein C and its regulation of blood coagulation. [NIH]
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Thrombopoietin: A humoral factor that controls blood platelet production through stimulation of megakaryocyte populations. Bone marrow megakaryocytes increase in both size and number in response to exposure to thrombopoietin. [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] Thymidine: A chemical compound found in DNA. Also used as treatment for mucositis. [NIH]
Thymidylate Synthase: An enzyme of the transferase class that catalyzes the reaction 5,10methylenetetrahydrofolate and dUMP to dihydrofolate and dTMP in the synthesis of thymidine triphosphate. (From Dorland, 27th ed) EC 2.1.1.45. [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] Tin: A trace element that is required in bone formation. It has the atomic symbol Sn, atomic number 50, and atomic weight 118.71. [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 Extracts: Preparations made from animal tissues or organs; they usually contain many components, any one of which may be pharmacologically or physiologically active; extracts may contain specific, but uncharacterized factors or proteins with specific actions. [NIH]
Tissue Preservation: The process by which a tissue or aggregate of cells is kept alive outside of the organism from which it was derived (i.e., kept from decay by means of a chemical agent, cooling, or a fluid substitute that mimics the natural state within the organism). [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] Tooth Preparation: Procedures carried out with regard to the teeth or tooth structures preparatory to specified dental therapeutic and surgical measures. [NIH] Topical: On the surface of the body. [NIH] Torsion: A twisting or rotation of a bodily part or member on its axis. [NIH] Toxic: Having to do with poison or something harmful to the body. Toxic substances
Dictionary 339
usually cause unwanted side effects. [NIH] Toxicity: The quality of being poisonous, especially the degree of virulence of a toxic microbe or of a poison. [EU] Toxicology: The science concerned with the detection, chemical composition, and pharmacologic action of toxic substances or poisons and the treatment and prevention of toxic manifestations. [NIH] Toxins: Specific, characterizable, poisonous chemicals, often proteins, with specific biological properties, including immunogenicity, produced by microbes, higher plants, or animals. [NIH] Toxoplasmosis: The acquired form of infection by Toxoplasma gondii in animals and man. [NIH]
Trace element: Substance or element essential to plant or animal life, but present in extremely small amounts. [NIH] Trachea: The cartilaginous and membranous tube descending from the larynx and branching into the right and left main bronchi. [NIH] Traction: The act of pulling. [NIH] Transcriptase: An enzyme which catalyses the synthesis of a complementary mRNA molecule from a DNA template in the presence of a mixture of the four ribonucleotides (ATP, UTP, GTP and CTP). [NIH] Transcription Factors: Endogenous substances, usually proteins, which are effective in the initiation, stimulation, or termination of the genetic transcription process. [NIH] Transduction: The transfer of genes from one cell to another by means of a viral (in the case of bacteria, a bacteriophage) vector or a vector which is similar to a virus particle (pseudovirion). [NIH] Transfection: The uptake of naked or purified DNA into cells, usually eukaryotic. It is analogous to bacterial transformation. [NIH] Transferases: Transferases are enzymes transferring a group, for example, the methyl group or a glycosyl group, from one compound (generally regarded as donor) to another compound (generally regarded as acceptor). The classification is based on the scheme "donor:acceptor group transferase". (Enzyme Nomenclature, 1992) EC 2. [NIH] Translation: The process whereby the genetic information present in the linear sequence of ribonucleotides in mRNA is converted into a corresponding sequence of amino acids in a protein. It occurs on the ribosome and is unidirectional. [NIH] 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] Trans-Splicing: The joining of RNA from two different genes. One type of trans-splicing is the "spliced leader" type (primarily found in protozoans such as trypanosomes and in lower invertebrates such as nematodes) which results in the addition of a capped, noncoding, spliced leader sequence to the 5' end of mRNAs. Another type of trans-splicing is the "discontinuous group II introns" type (found in plant/algal chloroplasts and plant mitochondria) which results in the joining of two independently transcribed coding
340 Glutathione
sequences. Both are mechanistically similar to conventional nuclear pre-mRNA cis-splicing. Mammalian cells are also capable of trans-splicing. [NIH] Trauma: Any injury, wound, or shock, must frequently physical or structural shock, producing a disturbance. [NIH] Treatment Outcome: Evaluation undertaken to assess the results or consequences of management and procedures used in combating disease in order to determine the efficacy, effectiveness, safety, practicability, etc., of these interventions in individual cases or series. [NIH]
Trees: Woody, usually tall, perennial higher plants (Angiosperms, Gymnosperms, and some Pterophyta) having usually a main stem and numerous branches. [NIH] Tremor: Cyclical movement of a body part that can represent either a physiologic process or a manifestation of disease. Intention or action tremor, a common manifestation of cerebellar diseases, is aggravated by movement. In contrast, resting tremor is maximal when there is no attempt at voluntary movement, and occurs as a relatively frequent manifestation of Parkinson disease. [NIH] Tretinoin: An important regulator of gene expression, particularly during growth and development and in neoplasms. Retinoic acid derived from maternal vitamin A is essential for normal gene expression during embryonic development and either a deficiency or an excess can be teratogenic. It is also a topical dermatologic agent which is used in the treatment of psoriasis, acne vulgaris, and several other skin diseases. It has also been approved for use in promyelocytic leukemia. [NIH] Trichloroethylene: A highly volatile inhalation anesthetic used mainly in short surgical procedures where light anesthesia with good analgesia is required. It is also used as an industrial solvent. Prolonged exposure to high concentrations of the vapor can lead to cardiotoxicity and neurological impairment. [NIH] Trichome: A filamentous or hairlike structure. [NIH] Trifluoperazine: A phenothiazine with actions similar to chlorpromazine. It is used as an antipsychotic and an antiemetic. [NIH] Troglitazone: A drug used in diabetes treatment that is being studied for its effect on reducing the risk of cancer cell growth in fat tissue. [NIH] Trophic: Of or pertaining to nutrition. [EU] 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] Trypan Blue: An azo that that is used in protozoal infections. [NIH] Trypanosomiasis: Infection with protozoa of the genus Trypanosoma. [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] Tuberculosis: Any of the infectious diseases of man and other animals caused by species of Mycobacterium. [NIH] Tuberous Sclerosis: A rare congenital disease in which the essential pathology is the appearance of multiple tumors in the cerebrum and in other organs, such as the heart or kidneys. [NIH] Tumor marker: A substance sometimes found in an increased amount in the blood, other
Dictionary 341
body fluids, or tissues and which may mean that a certain type of cancer is in the body. Examples of tumor markers include CA 125 (ovarian cancer), CA 15-3 (breast cancer), CEA (ovarian, lung, breast, pancreas, and gastrointestinal tract cancers), and PSA (prostate cancer). Also called biomarker. [NIH] Tumor model: A type of animal model which can be used to study the development and progression of diseases and to test new treatments before they are given to humans. Animals with transplanted human cancers or other tissues are called xenograft models. [NIH] Tumor Necrosis Factor: Serum glycoprotein produced by activated macrophages and other mammalian mononuclear leukocytes which has necrotizing activity against tumor cell lines and increases ability to reject tumor transplants. It mimics the action of endotoxin but differs from it. It has a molecular weight of less than 70,000 kDa. [NIH] Tumorigenic: Chemical, viral, radioactive or other agent that causes cancer; carcinogenic. [NIH]
Tumour: 1. Swelling, one of the cardinal signs of inflammations; morbid enlargement. 2. A new growth of tissue in which the multiplication of cells is uncontrolled and progressive; called also neoplasm. [EU] Tunicamycin: An N-acetylglycosamine containing antiviral antibiotic obtained from Streptomyces lysosuperificus. It is also active against some bacteria and fungi, because it inhibits the glucosylation of proteins. Tunicamycin is used as tool in the study of microbial biosynthetic mechanisms. [NIH] Type 2 diabetes: Usually characterized by a gradual onset with minimal or no symptoms of metabolic disturbance and no requirement for exogenous insulin. The peak age of onset is 50 to 60 years. Obesity and possibly a genetic factor are usually present. [NIH] Typhimurium: Microbial assay which measures his-his+ reversion by chemicals which cause base substitutions or frameshift mutations in the genome of this organism. [NIH] Tyrosine: A non-essential amino acid. In animals it is synthesized from phenylalanine. It is also the precursor of epinephrine, thyroid hormones, and melanin. [NIH] Ubiquitin: A highly conserved 76 amino acid-protein found in all eukaryotic cells. [NIH] 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] Ultraviolet Rays: That portion of the electromagnetic spectrum immediately below the visible range and extending into the x-ray frequencies. The longer wavelengths (near-UV or biotic or vital rays) are necessary for the endogenous synthesis of vitamin D and are also called antirachitic rays; the shorter, ionizing wavelengths (far-UV or abiotic or extravital rays) are viricidal, bactericidal, mutagenic, and carcinogenic and are used as disinfectants. [NIH]
Unconscious: Experience which was once conscious, but was subsequently rejected, as the "personal unconscious". [NIH] Univalent: Pertaining to an unpaired chromosome during the zygotene stage of prophase to first metaphase in meiosis. [NIH] 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] 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.
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[NIH]
Urethritis: Inflammation of the urethra. [EU] Uric: A kidney stone that may result from a diet high in animal protein. When the body breaks down this protein, uric acid levels rise and can form stones. [NIH] Urinary: Having to do with urine or the organs of the body that produce and get rid of urine. [NIH] Urine: Fluid containing water and waste products. Urine is made by the kidneys, stored in the bladder, and leaves the body through the urethra. [NIH] Urogenital: Pertaining to the urinary and genital apparatus; genitourinary. [EU] Uterus: The small, hollow, pear-shaped organ in a woman's pelvis. This is the organ in which a fetus develops. Also called the womb. [NIH] Vaccination: Administration of vaccines to stimulate the host's immune response. This includes any preparation intended for active immunological prophylaxis. [NIH] Vaccine: A substance or group of substances meant to cause the immune system to respond to a tumor or to microorganisms, such as bacteria or viruses. [NIH] Vacuole: A fluid-filled cavity within the cytoplasm of a cell. [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] Valves: Flap-like structures that control the direction of blood flow through the heart. [NIH] Vascular: Pertaining to blood vessels or indicative of a copious blood supply. [EU] Vascular endothelial growth factor: VEGF. A substance made by cells that stimulates new blood vessel formation. [NIH] Vascular Resistance: An expression of the resistance offered by the systemic arterioles, and to a lesser extent by the capillaries, to the flow of blood. [NIH] Vasculitis: Inflammation of a blood vessel. [NIH] Vasoactive: Exerting an effect upon the calibre of blood vessels. [EU] Vasoconstriction: Narrowing of the blood vessels without anatomic change, for which constriction, pathologic is used. [NIH] Vasodilation: Physiological dilation of the blood vessels without anatomic change. For dilation with anatomic change, dilatation, pathologic or aneurysm (or specific aneurysm) is used. [NIH] Vasodilator: An agent that widens blood vessels. [NIH] Vasogenic: Acute peripheral circulatory failure due to loss of capillary tone associated with a reduced circulating blood volume. [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]
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Ventral: 1. Pertaining to the belly or to any venter. 2. Denoting a position more toward the belly surface than some other object of reference; same as anterior in human anatomy. [EU] Ventricle: One of the two pumping chambers of the heart. The right ventricle receives oxygen-poor blood from the right atrium and pumps it to the lungs through the pulmonary artery. The left ventricle receives oxygen-rich blood from the left atrium and pumps it to the body through the aorta. [NIH] Ventricular: Pertaining to a ventricle. [EU] Venules: The minute vessels that collect blood from the capillary plexuses and join together to form veins. [NIH] Verapamil: A calcium channel blocker that is a class IV anti-arrhythmia agent. [NIH] Vertebrae: A bony unit of the segmented spinal column. [NIH] Vesicular: 1. Composed of or relating to small, saclike bodies. 2. Pertaining to or made up of vesicles on the skin. [EU] Vestibular: Pertaining to or toward a vestibule. In dental anatomy, used to refer to the tooth surface directed toward the vestibule of the mouth. [EU] Vestibule: A small, oval, bony chamber of the labyrinth. The vestibule contains the utricle and saccule, organs which are part of the balancing apparatus of the ear. [NIH] Veterinary Medicine: The medical science concerned with the prevention, diagnosis, and treatment of diseases in animals. [NIH] Vimentin: An intermediate filament protein found in most differentiating cells, in cells grown in tissue culture, and in certain fully differentiated cells. Its insolubility suggests that it serves a structural function in the cytoplasm. MW 52,000. [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] Virion: The infective system of a virus, composed of the viral genome, a protein core, and a protein coat called a capsid, which may be naked or enclosed in a lipoprotein envelope called the peplos. [NIH] Virulence: The degree of pathogenicity within a group or species of microorganisms or viruses as indicated by case fatality rates and/or the ability of the organism to invade the tissues of the host. [NIH] Virus: Submicroscopic organism that causes infectious disease. In cancer therapy, some viruses may be made into vaccines that help the body build an immune response to, and kill, tumor cells. [NIH] Viscera: Any of the large interior organs in any one of the three great cavities of the body, especially in the abdomen. [NIH] Viscosity: A physical property of fluids that determines the internal resistance to shear forces. [EU] Vitreous Hemorrhage: Hemorrhage into the vitreous body. [NIH] Vitro: Descriptive of an event or enzyme reaction under experimental investigation occurring outside a living organism. Parts of an organism or microorganism are used
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together with artificial substrates and/or conditions. [NIH] Vivo: Outside of or removed from the body of a living organism. [NIH] Volvulus: A twisting of the stomach or large intestine. May be caused by the stomach being in the wrong position, a foreign substance, or abnormal joining of one part of the stomach or intestine to another. Volvulus can lead to blockage, perforation, peritonitis, and poor blood flow. [NIH] White blood cell: A type of cell in the immune system that helps the body fight infection and disease. White blood cells include lymphocytes, granulocytes, macrophages, and others. [NIH]
Whooping Cough: A respiratory infection caused by Bordetella pertussis and characterized by paroxysmal coughing ending in a prolonged crowing intake of breath. [NIH] Whooping Cough: A respiratory infection caused by Bordetella pertussis and characterized by paroxysmal coughing ending in a prolonged crowing intake of breath. [NIH] Windpipe: A rigid tube, 10 cm long, extending from the cricoid cartilage to the upper border of the fifth thoracic vertebra. [NIH] Withdrawal: 1. A pathological retreat from interpersonal contact and social involvement, as may occur in schizophrenia, depression, or schizoid avoidant and schizotypal personality disorders. 2. (DSM III-R) A substance-specific organic brain syndrome that follows the cessation of use or reduction in intake of a psychoactive substance that had been regularly used to induce a state of intoxication. [EU] Womb: A hollow, thick-walled, muscular organ in which the impregnated ovum is developed into a child. [NIH] Wound Healing: Restoration of integrity to traumatized tissue. [NIH] Xanthine: An urinary calculus. [NIH] Xanthine Oxidase: An iron-molybdenum flavoprotein containing FAD that oxidizes hypoxanthine, some other purines and pterins, and aldehydes. Deficiency of the enzyme, an autosomal recessive trait, causes xanthinuria. EC 1.1.3.22. [NIH] Xenobiotics: Chemical substances that are foreign to the biological system. They include naturally occurring compounds, drugs, environmental agents, carcinogens, insecticides, etc. [NIH]
Xenograft: The cells of one species transplanted to another species. [NIH] X-ray: High-energy radiation used in low doses to diagnose diseases and in high doses to treat cancer. [NIH] X-ray therapy: The use of high-energy radiation from x-rays to kill cancer cells and shrink tumors. Radiation may come from a machine outside the body (external-beam radiation therapy) or from materials called radioisotopes. Radioisotopes produce radiation and can be placed in or near the tumor or in the area near cancer cells. This type of radiation treatment is called internal radiation therapy, implant radiation, interstitial radiation, or brachytherapy. Systemic radiation therapy uses a radioactive substance, such as a radiolabeled monoclonal antibody, that circulates throughout the body. X-ray therapy is also called radiation therapy, radiotherapy, and irradiation. [NIH] Yeasts: A general term for single-celled rounded fungi that reproduce by budding. Brewers' and bakers' yeasts are Saccharomyces cerevisiae; therapeutic dried yeast is dried yeast. [NIH] Yohimbine: A plant alkaloid with alpha-2-adrenergic blocking activity. Yohimbine has been used as a mydriatic and in the treatment of impotence. It is also alleged to be an aphrodisiac. [NIH]
Dictionary 345
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]
347
INDEX 1 1-Methyl-4-phenyl-1,2,3,6tetrahydropyridine, 62, 245 A Abdomen, 245, 258, 296, 300, 313, 315, 332, 333, 343 Abdominal, 245, 284, 313, 315, 325, 341 Abdominal Pain, 245, 284, 315, 341 Aberrant, 41, 245 Ablation, 97, 197, 245 Abscess, 245, 287 Absenteeism, 180, 245 Acatalasia, 245, 261 Acceptor, 245, 300, 312, 323, 339 Acetaldehyde, 80, 245, 248 Acetaminophen, 10, 72, 138, 148, 245, 284 Acetone, 183, 245, 298 Acetylcholine, 245, 264, 309 Acetylcysteine, 15, 30, 39, 77, 132, 141, 146, 153, 162, 173, 199, 218, 245 Aclarubicin, 150, 245 Acne, 168, 208, 245, 246, 256, 340 Acne Vulgaris, 208, 246, 340 Actin, 246, 307, 308, 340 Action Potentials, 62, 246 Acute leukemia, 246, 279, 337 Acute lymphoblastic leukemia, 93, 246 Acute lymphocytic leukemia, 246 Acute myelogenous leukemia, 246 Acute myeloid leukemia, 108, 246, 320 Acute nonlymphocytic leukemia, 246 Acyl, 38, 246 Adaptability, 246, 262 Adaptation, 6, 55, 213, 246, 264, 306 Adduct, 20, 34, 35, 43, 63, 246, 337 Adduction, 28, 246 Adenine, 43, 203, 246, 323 Adenocarcinoma, 27, 103, 110, 246, 290, 310, 321 Adenosine, 165, 246, 292, 316 Adenosine Triphosphate, 165, 246, 316 Adenovirus, 57, 246 Adenylate Cyclase, 246, 283 Adipose Tissue, 102, 247 Adjustment, 246, 247 Adolescence, 20, 247 Adrenal Cortex, 247, 270, 291, 311, 320, 326
Adrenal Glands, 247, 325 Adrenergic, 152, 153, 247, 252, 275, 279, 335, 344 Adverse Effect, 22, 51, 194, 195, 247, 276, 297, 326, 330 Aerobic, 44, 48, 56, 247, 305, 313 Aerobic Metabolism, 56, 247, 313 Aerobic Respiration, 247, 313 Aerosol, 65, 247, 310, 335 Affinity, 33, 38, 71, 75, 163, 164, 167, 170, 186, 198, 200, 247, 248, 254, 302, 304, 331 Affinity Chromatography, 198, 247 Affinity Labels, 38, 247 Aflatoxins, 61, 247 Agar, 248, 267, 270, 317 Age of Onset, 44, 110, 248, 341 Ageing, 106, 152, 205, 248 Aggressiveness, 119, 248 Agonist, 248, 275, 309 Air Pollutants, 28, 248 Airway, 21, 218, 248 Albumin, 102, 248, 317, 336 Alcohol Dehydrogenase, 52, 63, 113, 153, 248 Aldehyde Dehydrogenase, 52, 93, 248 Aldehyde Reductase, 9, 156, 248 Aldehydes, 9, 37, 56, 80, 248, 344 Alfalfa, 154, 248 Algorithms, 248, 257 Alimentary, 107, 248, 313 Alkaline, 248, 250, 260, 313, 337 Alkaloid, 152, 248, 260, 267, 309, 326, 344 Alkylate, 20, 248 Alkylating Agents, 20, 34, 69, 78, 192, 248, 259, 264 Alkylation, 34, 50, 249 Alleles, 19, 33, 59, 249, 290 Allografts, 249, 290 Allopurinol, 165, 249 Allylamine, 249 Alopecia, 249, 271 Alpha Particles, 249, 324 Alpha-1, 103, 229, 249 Alternative medicine, 59, 219, 249 Ambulatory Care, 249 Ameliorated, 155, 249 Ameliorating, 151, 168, 169, 177, 197, 249 Amine, 162, 249, 290
348 Glutathione
Amino Acid Sequence, 32, 64, 155, 158, 170, 200, 249, 251, 285 Aminoethyl, 180, 250 Ammonia, 249, 250, 287, 341 Amputation, 40, 250 Amyloid, 9, 42, 148, 250 Anaerobic, 44, 48, 69, 250 Anaesthesia, 250, 294 Anal, 27, 250, 279, 282 Analgesic, 245, 250, 299, 307, 310 Analog, 37, 207, 250 Analogous, 250, 318, 339 Analytes, 250, 335 Anaphylatoxins, 250, 268 Anaplasia, 250, 321 Anatomical, 250, 254, 269, 274, 293, 328 Anemia, 90, 122, 125, 230, 231, 250, 259, 283, 289, 306 Anesthesia, 248, 250, 277, 340 Aneurysm, 250, 342 Angina, 178, 250, 309, 310 Angiogenesis, 250, 302 Angioplasty, 116, 178, 250 Animal model, 4, 5, 18, 23, 38, 49, 58, 60, 251, 341 Anions, 248, 251, 296, 330, 334 Anorexia, 172, 176, 251, 284 Antagonism, 10, 251 Anthracycline, 245, 251, 272, 279, 292 Antiarrhythmic, 62, 251 Antibacterial, 183, 251, 274, 332 Antibiotic, 245, 251, 255, 259, 272, 275, 279, 280, 292, 314, 332, 337, 341 Anticoagulant, 161, 251, 321 Antidote, 251, 260 Antiemetic, 251, 252, 264, 340 Antigen, 70, 86, 167, 190, 247, 251, 268, 272, 277, 279, 285, 291, 292, 293, 294, 303, 335 Antigen-Antibody Complex, 251, 268 Antigen-presenting cell, 70, 251, 272 Antihypertensive, 251, 283, 309, 326 Anti-infective, 252, 291, 331 Anti-inflammatory, 162, 172, 178, 183, 245, 252, 286, 313, 327 Antimetabolite, 193, 252, 337 Antimicrobial, 252, 275 Antineoplastic, 245, 249, 252, 260, 271, 275, 284, 303, 309, 313, 316, 334, 337, 343 Antineoplastic Agents, 249, 252, 309, 316, 343 Antipsychotic, 252, 264, 326, 340
Antipyretic, 245, 252 Antiseptic, 245, 252, 261 Antiviral, 245, 252, 284, 293, 295, 314, 341 Anus, 250, 252 Anxiety, 252, 297 Aorta, 37, 252, 325, 343 Apolipoproteins, 252, 300 Apoptosis, 9, 10, 11, 14, 16, 18, 24, 29, 30, 39, 47, 56, 82, 95, 111, 115, 135, 195, 252, 253, 261 Aqueous, 173, 253, 255, 265, 271, 277, 291, 299 Aqueous fluid, 173, 253 Arachidonate 12-Lipoxygenase, 253, 300 Arachidonate 15-Lipoxygenase, 253, 300 Arachidonate Lipoxygenases, 253, 300 Arachidonic Acid, 41, 253, 299, 321 Arginine, 153, 165, 192, 215, 250, 253, 309 Aromatic, 54, 100, 253, 287, 304, 316, 334 Arrhythmia, 251, 253, 343 Arsenic trioxide, 82, 92, 95, 117, 123, 124, 125, 126, 253 Arterial, 181, 249, 253, 259, 260, 263, 264, 292, 296, 310, 322, 336 Arteries, 153, 181, 252, 253, 258, 263, 265, 269, 301, 304, 307, 338 Arteriolar, 253, 258, 326 Arterioles, 173, 181, 253, 258, 260, 342 Arteriolosclerosis, 253 Arteriosclerosis, 181, 253 Arteriovenous, 253, 263 Asbestos, 253, 254 Asbestosis, 162, 253, 254 Ascites, 187, 254 Ascorbic Acid, 65, 70, 92, 105, 117, 123, 124, 125, 126, 166, 171, 208, 254, 292 Aspartate, 163, 254 Asphyxia, 254, 310 Assay, 29, 33, 42, 254, 293, 341 Astringent, 174, 254, 261 Astrocytes, 12, 41, 122, 124, 131, 148, 163, 254 Astrocytoma, 254, 286 Asymptomatic, 116, 245, 254, 287 Ataxia, 79, 231, 254, 337 Atmospheric Pressure, 254, 292 Atopic, 189, 254 Atrium, 254, 343 Atrophy, 102, 230, 231, 254, 308 Attenuated, 56, 66, 254, 274 Attenuation, 7, 254 Auditory, 23, 53, 254, 288, 328
Index 349
Aura, 99, 254 Autoimmune disease, 189, 254, 255, 306 Autoimmunity, 98, 255 Autologous, 189, 255 Autopsy, 6, 255 Auxin, 64, 74, 255 Axillary, 154, 255 Axons, 255, 311, 327 Azithromycin, 150, 255 B Bacterial Physiology, 246, 255 Bactericidal, 255, 280, 341 Bacteriophage, 255, 317, 339 Bacteriostatic, 255, 280 Bacterium, 255, 267, 268 Basal Ganglia, 81, 252, 254, 255, 259, 286, 292 Basal Ganglia Diseases, 254, 255, 292 Base, 4, 33, 48, 67, 68, 191, 246, 255, 260, 271, 272, 283, 285, 297, 336, 341 Basement Membrane, 255, 281 Benign, 80, 253, 255, 288, 308, 324 Benign tumor, 80, 255 Benzoic Acid, 162, 256 Benzoyl Peroxide, 208, 256 Beta Rays, 256, 277 Beta-Galactosidase, 256, 298 Beta-pleated, 250, 256 Bile, 86, 256, 286, 291, 297, 300, 329, 333, 336 Bile Acids, 256, 333, 336 Bile Acids and Salts, 256 Bile Pigments, 256, 297 Bilirubin, 248, 256, 286, 292 Binding Sites, 78, 163, 256 Bioavailability, 40, 214, 256 Biochemical reactions, 256, 337 Biogenesis, 196, 256 Biological Markers, 27, 256 Biological response modifier, 256, 257, 295 Biological therapy, 256, 288 Biomarkers, 21, 26, 39, 54, 83, 92, 110, 118, 134, 257 Biomolecular, 257, 335 Bioreactors, 159, 257 Biosynthesis, 22, 30, 69, 73, 78, 84, 86, 194, 253, 257, 283 Biotechnology, 63, 79, 123, 125, 214, 219, 225, 228, 230, 231, 232, 257 Biotic, 257, 341 Biotransformation, 31, 60, 155, 184, 257 Bivalent, 108, 257, 304
Bladder, 39, 110, 119, 257, 271, 294, 306, 321, 341, 342 Blastocyst, 257, 268, 317 Blasts, 192, 257 Blennorrhoea, 257, 287 Blood Cell Count, 257, 289 Blood Coagulation, 257, 260, 337 Blood Glucose, 257, 289, 295 Blood Platelets, 257, 303, 329, 337 Blood pressure, 181, 251, 258, 260, 261, 292, 305, 315, 331 Blood Volume, 258, 342 Blood-Brain Barrier, 45, 258 Blot, 38, 47, 158, 258, 293 Blotting, Western, 258, 293 Body Fluids, 42, 257, 258, 331, 341 Body Mass Index, 17, 258 Bolus, 166, 258 Bolus infusion, 258 Bone Marrow, 23, 32, 57, 164, 207, 246, 258, 267, 280, 301, 303, 306, 320, 331, 333 Bone Marrow Cells, 32, 57, 258, 267, 303 Bone Marrow Transplantation, 57, 258 Boron, 155, 258, 271 Boron Neutron Capture Therapy, 258 Bowel, 164, 190, 250, 258, 294, 296, 299, 315, 333, 341 Brachytherapy, 258, 296, 297, 324, 344 Bradykinin, 156, 258, 297, 309, 317 Brain Hypoxia, 259, 337 Brain Infarction, 259 Brain Ischemia, 41, 259, 263 Brain Stem, 259, 263, 308 Branch, 241, 259, 271, 277, 301, 314, 322, 325, 332, 337 Breakdown, 44, 259, 263, 274, 284, 311 Breeding, 63, 192, 259 Broad-spectrum, 24, 259 Bromine, 209, 259 Bronchi, 259, 279, 339 Bronchial, 21, 259, 290 Bronchiseptica, 259, 315 Bronchitis, 259, 265 Burns, 137, 168, 169, 172, 256, 259 Burns, Electric, 259 Busulfan, 108, 259 C Cachexia, 190, 259 Cadmium, 30, 64, 68, 74, 132, 184, 259 Cadmium Poisoning, 259 Calcification, 253, 259 Calcium Chloride, 165, 260
350 Glutathione
Calmodulin, 260, 309 Camptothecin, 88, 122, 124, 131, 260 Canonical, 13, 260 Capillary, 41, 258, 260, 327, 342, 343 Capillary Permeability, 259, 260 Capsid, 102, 260, 343 Capsules, 260, 275, 285 Captopril, 153, 260 Carbohydrate, 215, 260, 287, 319 Carbon Dioxide, 260, 272, 282, 284, 317, 326 Carboplatin, 24, 27, 192, 260 Carboxy, 170, 260 Carboxy-terminal, 170, 260 Carcinogen, 21, 31, 36, 39, 60, 83, 132, 201, 246, 260, 280, 303, 306 Carcinogenesis, 4, 31, 32, 36, 39, 44, 61, 67, 83, 88, 93, 113, 130, 135, 156, 175, 212, 260, 264 Carcinogenic, 9, 28, 39, 54, 61, 156, 205, 249, 261, 294, 310, 311, 320, 333, 341 Carcinoma, 97, 101, 107, 110, 134, 146, 261, 310 Cardiac, 50, 62, 166, 217, 245, 249, 251, 261, 278, 279, 292, 307, 326, 333 Cardiotoxicity, 261, 279, 340 Cardiovascular, 26, 83, 96, 151, 152, 177, 178, 180, 181, 261, 299, 329 Cardiovascular disease, 83, 151, 177, 181, 261 Cardiovascular System, 152, 181, 261 Carnitine, 152, 261 Carotene, 129, 261, 326 Carrier Proteins, 29, 261, 317 Case report, 11, 261, 266, 282 Case series, 261, 266 Caspase, 10, 11, 29, 46, 82, 85, 261 Catabolism, 34, 70, 73, 261 Catalase, 7, 23, 49, 50, 52, 56, 91, 102, 151, 156, 174, 175, 177, 245, 261 Catalytic Domain, 170, 261 Cataract, 18, 38, 261 Catechol, 49, 261 Catecholamine, 261, 275 Catheterization, 251, 262 Cathode, 256, 262, 277 Cations, 165, 262, 296 Caudal, 262, 273, 319 Causal, 58, 262, 279 Cause of Death, 40, 181, 197, 262 Caustic, 262, 331 Cell Count, 53, 262
Cell Cycle, 10, 14, 21, 39, 43, 97, 262, 265, 271, 322, 342 Cell Death, 10, 11, 14, 35, 44, 47, 49, 55, 57, 58, 85, 89, 96, 113, 191, 195, 252, 253, 262, 285, 307 Cell Differentiation, 39, 262, 330 Cell Division, 35, 78, 230, 255, 262, 271, 288, 303, 304, 305, 317, 320, 329, 336 Cell Extracts, 20, 262 Cell membrane, 38, 53, 150, 163, 164, 201, 209, 261, 262, 273, 284, 316, 335 Cell Membrane Permeability, 201, 262 Cell proliferation, 31, 32, 36, 38, 39, 40, 190, 193, 253, 262, 330 Cell Respiration, 74, 247, 262, 305, 313, 326 Cell Size, 262, 283 Cell Survival, 46, 59, 171, 262, 288 Cellular metabolism, 168, 169, 262 Cellulose, 263, 317 Central Nervous System Infections, 263, 288 Centrifugation, 263, 289, 305 Cerebellar, 164, 180, 254, 263, 325, 340 Cerebellum, 259, 263, 325 Cerebral, 41, 152, 159, 181, 254, 255, 258, 259, 263, 279, 281, 286, 308, 336 Cerebral hemispheres, 255, 259, 263, 286, 336 Cerebral Infarction, 259, 263 Cerebrospinal, 108, 263 Cerebrospinal fluid, 108, 263 Cerebrovascular, 181, 255, 261, 263, 337 Cerebrovascular Disorders, 181, 263, 337 Cerebrum, 263, 336, 340 Cervical, 164, 263 Cervix, 263, 326 Character, 264, 272 Chelation, 47, 264 Chemoprevention, 31, 264 Chemopreventive, 34, 39, 45, 130, 264 Chemotactic Factors, 264, 268 Chemotherapeutics, 195, 264 Chlorambucil, 192, 264 Chlorine, 66, 68, 209, 264 Chlorine Compounds, 66, 264 Chlorophyll, 65, 264 Chloroplasts, 67, 264, 339 Chlorpromazine, 203, 264, 340 Cholesterol, 45, 57, 171, 181, 256, 264, 265, 269, 300, 301, 333 Cholesterol Esters, 264, 300 Choline, 195, 264
Index 351
Cholinergic, 252, 264, 309 Chondroitin sulfate, 203, 264 Choroid, 265, 326, 327 Chromatin, 19, 252, 265, 332, 336 Chromium, 28, 48, 265, 278 Chromium Compounds, 28, 265 Chromosomal, 4, 26, 165, 265, 304, 317, 327 Chromosome, 4, 6, 192, 265, 268, 288, 300, 304, 329, 341 Chronic Disease, 10, 259, 265, 267, 299 Chronic Fatigue Syndrome, 190, 265 Chronic Obstructive Pulmonary Disease, 118, 151, 177, 265 Chronic renal, 265, 318 Chylomicrons, 265, 300 Ciliary, 173, 253, 265, 330 Ciliary Arteries, 173, 265 Ciliary Body, 265, 330 Ciliary processes, 253, 265 CIS, 25, 27, 56, 64, 92, 113, 118, 265, 326, 340 Cisplatin, 23, 54, 60, 71, 104, 114, 127, 133, 192, 265 Citric Acid, 161, 265 Citrus, 254, 265 Clamp, 62, 265 Clear cell carcinoma, 266, 273, 274 Clinical Medicine, 100, 101, 120, 266, 319 Clinical study, 51, 266 Clinical trial, 4, 53, 54, 159, 225, 226, 266, 269, 324 Clitoral, 153, 266 Clone, 9, 18, 159, 266 Cloning, 14, 16, 29, 66, 68, 69, 123, 125, 130, 146, 257, 266, 299 Coagulation, 178, 257, 266, 289, 317, 338 Coal, 54, 266 Cochlea, 23, 266, 295 Cochlear, 23, 53, 266, 333 Cochlear Duct, 266, 333 Codon, 44, 76, 158, 266, 285, 329 Coenzyme, 139, 151, 178, 254, 266, 298 Cofactor, 62, 266, 321, 337 Cohort Studies, 266, 279 Colchicine, 150, 267 Colitis, 146, 162, 267 Collagen, 24, 205, 255, 267, 281, 282, 285, 291, 302, 318, 320 Collagen disease, 267, 291 Collapse, 259, 267 Colloidal, 248, 267, 277, 330, 335
Colony-Stimulating Factors, 267, 288 Colorectal, 31, 43, 88, 94, 97, 110, 137, 267 Colorectal Cancer, 43, 88, 94, 97, 137, 267 Colostrum, 202, 267 Combination chemotherapy, 33, 267 Combination Therapy, 226, 267 Compacta, 61, 267 Competency, 107, 267 Complement, 14, 202, 250, 267, 268, 285, 317 Complementary and alternative medicine, 129, 143, 268 Complementary medicine, 129, 268 Complementation, 69, 268 Complete remission, 268, 325 Computational Biology, 225, 228, 268 Conception, 51, 268, 282, 333 Concomitant, 157, 268 Cones, 268, 327 Conjugated, 157, 194, 206, 256, 268, 271 Conjugation, 17, 18, 25, 35, 88, 122, 124, 131, 155, 194, 212, 257, 268, 286 Conjunctiva, 265, 269 Connective Tissue, 174, 254, 258, 267, 269, 282, 284, 285, 301, 304, 327, 328, 333, 336 Connective Tissue Cells, 269 Consciousness, 250, 269, 272, 275, 326 Constitutional, 269, 307 Constriction, 269, 297, 342 Constriction, Pathologic, 269, 342 Consultation, 161, 269 Consumption, 49, 98, 101, 107, 153, 154, 157, 215, 269, 273, 284, 310, 313 Contamination, 171, 269, 290 Contractility, 49, 269 Contraindications, ii, 226, 269 Contralateral, 17, 269, 304, 311, 325 Control group, 54, 269 Controlled study, 98, 269 Coordination, 263, 269, 306 Cornea, 156, 253, 269, 287, 328 Corneum, 190, 269, 279 Coronary, 83, 96, 181, 218, 261, 269, 304, 307, 309, 310 Coronary heart disease, 181, 261, 269 Coronary Thrombosis, 269, 304, 307 Corpus, 270, 314, 320 Cortex, 254, 270, 281, 290, 308, 325 Cortical, 270, 281, 329, 337 Corticosteroids, 172, 270, 286 Cortisol, 248, 270 Cranial, 263, 270, 288, 310, 311, 315
352 Glutathione
Craniocerebral Trauma, 255, 270, 288, 337 Creatine, 109, 270 Creatine Kinase, 109, 270 Creatinine, 270 Critical Care, 8, 27, 80, 270 Cross-Sectional Studies, 270, 279 Cryptosporidiosis, 255, 270 Crystallization, 35, 52, 270 Culture Media, 171, 248, 270 Cultured cells, 15, 18, 25, 270 Cumulative Trauma Disorders, 162, 270 Curative, 270, 337 Curcumin, 183, 270 Cutaneous, 151, 168, 169, 171, 172, 177, 189, 271, 287, 301, 317 Cyclic, 246, 260, 271, 283, 288, 309, 321, 328 Cyclin, 43, 271 Cyclophosphamide, 50, 139, 150, 192, 271, 292 Cystine, 41, 63, 114, 151, 165, 179, 271, 275 Cystitis, 162, 271 Cytochrome, 10, 29, 52, 56, 86, 92, 93, 104, 120, 132, 156, 271 Cytogenetics, 5, 271 Cytokine, 14, 21, 24, 99, 182, 271 Cytoplasm, 29, 165, 252, 262, 271, 276, 281, 288, 304, 308, 327, 336, 342, 343 Cytoprotection, 81, 91, 271 Cytosine, 36, 48, 271 Cytoskeletal Proteins, 170, 201, 271 Cytoskeleton, 271, 305 Cytotoxic, 16, 18, 32, 34, 37, 38, 44, 160, 192, 193, 195, 209, 271, 324, 330 Cytotoxicity, 12, 18, 34, 59, 90, 108, 112, 249, 265, 271, 298 D Dairy Products, 157, 272 Databases, Bibliographic, 225, 272 Daunorubicin, 82, 150, 192, 245, 272, 275 De novo, 25, 55, 272 Deamination, 272, 341 Decarboxylation, 272, 290, 323 Decidua, 272, 317 Decision Making, 17, 272 Defense Mechanisms, 37, 56, 200, 272 Degenerative, 35, 180, 181, 272, 289, 302 Dehydration, 179, 272 Dehydroepiandrosterone, 180, 272 Deletion, 63, 83, 192, 252, 272 Dementia, 252, 272, 308 Denaturation, 161, 187, 272
Dendrites, 272, 308 Dendritic, 14, 164, 190, 272, 303, 327 Dendritic cell, 14, 164, 190, 272 Density, 12, 160, 202, 258, 263, 272, 283, 300, 311, 318 Deoxyguanosine, 42, 272 Depolarization, 57, 163, 273, 330 Deprivation, 8, 12, 273 Depsipeptide, 103, 273 Dermal, 168, 205, 273 Dermatitis, 137, 172, 273, 276 DES, 250, 273 Deuterium, 51, 273, 291 Developing Countries, 273, 336 Dextroamphetamine, 273, 304 Diabetes Mellitus, 29, 40, 173, 273, 286, 289 Diabetic Retinopathy, 105, 146, 273, 317 Diagnostic procedure, 149, 219, 273 Dialyzer, 273, 289 Diastole, 273 Diastolic, 50, 273, 292 Diencephalon, 263, 273, 308, 336 Dietary Fats, 273, 300 Diethylcarbamazine, 273, 334 Diethylstilbestrol, 90, 273 Diffusion, 260, 274 Digestion, 196, 215, 248, 256, 258, 274, 296, 300, 333 Digestive tract, 274, 331, 332 Dihydrotestosterone, 274, 325 Dilatation, 250, 274, 320, 342 Dilatation, Pathologic, 274, 342 Dilation, 153, 258, 274, 342 Dilator, 274, 310 Dilution, 74, 109, 274 Dimethyldithiocarbamate, 147, 274 Dipeptides, 163, 274 Diphtheria, 72, 274 Diphtheria Toxin, 72, 274 Diploid, 268, 274, 317 Direct, iii, 4, 9, 25, 42, 43, 48, 49, 58, 62, 187, 266, 274, 275, 325, 335 Disease Progression, 50, 274 Disease Susceptibility, 22, 274 Disease-Free Survival, 17, 274 Disinfectant, 274, 280 Disinfection, 100, 274 Dissociation, 247, 274, 296 Distal, 153, 275, 298, 322 Disulphides, 275 Dithiothreitol, 55, 67, 275
Index 353
Diuretic, 174, 260, 275, 331 Dizziness, 179, 197, 275 Dopamine, 20, 58, 61, 108, 252, 264, 273, 274, 275, 316 Dorsal, 275, 319 Dosage Forms, 208, 275 Dose-limiting, 23, 60, 275 Doxorubicin, 11, 24, 59, 150, 192, 245, 275, 279 Doxycycline, 55, 57, 275 Drug Interactions, 275 Drug Resistance, 17, 19, 25, 32, 45, 94, 114, 119, 135, 195, 212, 275, 276 Drug Tolerance, 275, 276, 338 Drug Toxicity, 199, 276 Duodenum, 256, 276, 329, 333 Dyes, 16, 250, 276, 283 Dyspareunia, 153, 276 Dysplasia, 231, 276 Dystrophy, 162, 230, 276 E Echocardiography, 50, 276 Eczema, 172, 276 Edema, 41, 162, 273, 276, 306, 319 Effector, 245, 267, 276, 298, 309 Effector cell, 276, 298, 309 Efficacy, 8, 17, 24, 33, 34, 39, 53, 54, 61, 90, 155, 191, 207, 208, 276, 340 Egg Yolk, 203, 276 Ejaculation, 276, 329 Elasticity, 181, 253, 276, 331 Elastin, 267, 276, 281 Elective, 135, 276 Electrocoagulation, 266, 276 Electrolysis, 251, 262, 276, 277 Electrolyte, 202, 276, 319, 331 Electrons, 43, 252, 255, 256, 262, 276, 296, 312, 324, 335 Electrophoresis, 48, 277 Electrophysiological, 62, 277 Electroplating, 261, 277 Elementary Particles, 276, 277, 309, 322 ELISA, 42, 102, 186, 187, 277 Emboli, 116, 277, 296 Embolization, 116, 277 Embolus, 277, 294, 296 Embryo, 32, 257, 262, 276, 277, 294, 311, 318 Emphysema, 265, 277 Emulsion, 277, 283 Enalapril, 117, 277 Encapsulated, 166, 205, 277
Encephalopathy, 171, 277 Endarterectomy, 251, 277 Endemic, 277, 332 Endocarditis, 277, 287 Endometrial, 278 Endometriosis, 98, 278 Endometrium, 272, 278, 303 Endothelial cell, 15, 37, 41, 105, 112, 115, 123, 125, 135, 158, 164, 190, 258, 278, 282, 337 Endothelium, 37, 40, 152, 278, 309 Endothelium, Lymphatic, 278 Endothelium, Vascular, 278 Endothelium-derived, 40, 152, 278, 309 Endotoxic, 278, 300 Endotoxin, 5, 15, 278, 341 End-stage renal, 265, 278, 318 Enhancer, 65, 182, 194, 204, 278, 326 Enkephalins, 278 Enterochromaffin Cells, 164, 278 Environmental Exposure, 4, 28, 49, 256, 278, 311 Environmental Health, 21, 22, 27, 29, 55, 60, 94, 224, 226, 278 Environmental Pollutants, 59, 278 Environmental tobacco smoke, 21, 279 Enzyme, 10, 13, 18, 25, 27, 31, 33, 34, 36, 37, 38, 41, 42, 47, 49, 52, 55, 56, 58, 59, 61, 62, 69, 71, 73, 119, 131, 132, 145, 146, 153, 154, 158, 159, 164, 167, 177, 186, 187, 191, 192, 196, 211, 213, 246, 248, 253, 256, 257, 260, 261, 266, 276, 277, 279, 282, 284, 287, 288, 291, 297, 298, 299, 300, 304, 313, 314, 315, 317, 318, 321, 322, 325, 330, 334, 337, 338, 339, 343, 344, 345 Enzyme Induction, 52, 279 Enzyme Inhibitors, 279, 317 Enzyme-Linked Immunosorbent Assay, 186, 279 Epidemic, 164, 279, 332 Epidemiologic Studies, 22, 256, 279 Epidemiological, 17, 31, 60, 279, 282 Epidermal, 82, 86, 91, 92, 168, 169, 279, 297, 303 Epidermal Growth Factor, 82, 168, 169, 279 Epidermis, 190, 269, 279, 291, 297, 302, 320, 323 Epidermoid carcinoma, 87, 279, 332 Epinephrine, 247, 275, 279, 310, 341 Epirubicin, 150, 192, 279
354 Glutathione
Epithelial, 5, 15, 18, 21, 38, 39, 51, 52, 60, 85, 88, 89, 94, 106, 156, 175, 246, 265, 272, 279, 280 Epithelial Cells, 15, 21, 39, 85, 88, 89, 106, 156, 175, 279, 280 Epithelium, 31, 39, 65, 81, 102, 255, 278, 280, 296, 321 Epitope, 72, 280 Erectile, 178, 280, 314 Erection, 153, 280 Erythema, 280, 334 Erythrocytes, 84, 100, 106, 117, 130, 230, 250, 257, 258, 280, 325 Erythromycin, 150, 255, 280 Erythropoietin, 90, 122, 125, 280 Esophageal, 93, 101, 178, 280 Esophageal Spasms, 178, 280 Esophagus, 96, 151, 177, 274, 280, 316, 333 Essential Tremor, 230, 280 Estrogen, 109, 180, 280 Ethanol, 5, 15, 52, 58, 147, 248, 280, 282 Ethanolamine, 70, 171, 280 Ethoxyquin, 9, 61, 280 Ethylene Dibromide, 156, 280 Eukaryotic Cells, 271, 281, 294, 312, 341 Evoke, 281, 333 Excitation, 281, 283 Excitatory, 41, 163, 281, 286, 287 Excitotoxicity, 41, 135, 281 Exfoliation, 168, 281 Exhaustion, 251, 281 Exogenous, 23, 24, 36, 49, 65, 68, 176, 185, 189, 257, 260, 276, 281, 285, 286, 341 Exons, 6, 281 Expiration, 281, 326 External-beam radiation, 281, 297, 324, 344 Extracellular Matrix, 205, 269, 281, 282, 302 Extracellular Matrix Proteins, 281, 302 Extracellular Space, 41, 163, 281 Extracorporeal, 117, 159, 281 Extracorporeal Circulation, 117, 281 Extraction, 48, 281 Extrapyramidal, 252, 275, 281 Eye Infections, 246, 281 F Facial, 45, 281, 314 Fallopian Tubes, 281, 326 Family Planning, 225, 282 Fatal Outcome, 282, 323 Fatigue, 176, 265, 282, 289
Fatty acids, 59, 123, 126, 248, 282, 286, 287, 300, 321, 331, 338 Fermentation, 179, 248, 282 Ferritin, 109, 282 Fertilizers, 154, 282 Fetus, 51, 280, 282, 283, 317, 320, 342 Fibrin, 257, 282, 315, 337, 338 Fibroblast Growth Factor, 24, 282 Fibroblasts, 4, 15, 59, 89, 117, 269, 282, 295 Fibrosis, 3, 27, 106, 150, 231, 249, 282, 328 Fixation, 154, 282 Flatus, 283, 284 Flow Cytometry, 29, 198, 283 Fluorescence, 4, 13, 15, 283 Fluorescent Dyes, 283 Foetoplacental, 283, 311 Folate, 44, 283 Fold, 6, 24, 30, 31, 36, 51, 283 Folic Acid, 157, 283, 323 Forearm, 40, 258, 283 Forskolin, 123, 125, 283 Fovea, 282, 283 Fractionation, 47, 59, 283 Frameshift, 283, 341 Frameshift Mutation, 283, 341 Friction, 283, 301 Fructans, 154, 284 Fructose, 284 Fulminant Hepatic Failure, 159, 284 Fungi, 268, 281, 284, 288, 304, 305, 307, 332, 341, 344 Fungicide, 201, 284 Fungistatic, 256, 284 G Gallate, 122, 124, 131, 284 Gamma Rays, 284, 307, 324 Gamma-Glutamyltransferase, 114, 284 Gamma-interferon, 284, 295 Ganglia, 245, 255, 284, 308, 315 Gap Junctions, 284, 335, 336 Gas, 54, 151, 250, 260, 264, 274, 280, 283, 284, 291, 306, 309, 310, 323, 326, 335 Gas exchange, 284, 326 Gasoline, 280, 284 Gastric, 111, 261, 275, 278, 279, 284, 290 Gastrin, 284, 291 Gastritis, 137, 162, 284 Gastroenteritis, 259, 284 Gastrointestinal, 94, 135, 183, 188, 202, 215, 253, 259, 279, 280, 285, 299, 329, 334, 341
Index 355
Gastrointestinal tract, 135, 183, 215, 280, 285, 299, 329, 341 Gelatin, 270, 285, 287, 337 Gene Expression, 10, 12, 16, 19, 36, 39, 42, 46, 47, 50, 59, 66, 193, 231, 285, 340 Gene Silencing, 36, 285 Gene Targeting, 30, 285 Generator, 16, 205, 285 Genetic Code, 285, 310 Genetic Engineering, 58, 257, 266, 285, 324 Genetic Markers, 17, 21, 285 Genetics, 4, 18, 27, 79, 91, 268, 271, 285 Genital, 153, 266, 285, 342 Genitourinary, 93, 285, 342 Genitourinary system, 93, 285 Genotype, 22, 26, 27, 30, 71, 72, 90, 96, 101, 110, 118, 249, 285, 316 Geriatric, 161, 176, 285 Germ Cells, 285, 303, 312, 331, 332, 337 Germline mutation, 43, 285, 290 Gestation, 285, 314, 317, 319 Giant Cells, 285, 328 Ginger, 133, 142, 286 Ginseng, 141, 286 Gland, 247, 286, 301, 313, 314, 317, 321, 329, 333, 334, 338 Glioblastoma, 113, 286 Glioma, 19, 40, 286 Glottis, 286, 290, 315 Glucocorticoid, 66, 286, 291 Glucose, 62, 64, 91, 94, 161, 203, 209, 230, 254, 257, 263, 265, 273, 286, 289, 295, 328, 331 Glucose Intolerance, 273, 286 Glucosinolates, 60, 286 Glucuronic Acid, 196, 286, 289 Glucuronides, 286 Glucuronosyltransferase, 49, 286 Glutamate, 30, 41, 133, 135, 163, 166, 180, 212, 281, 286, 287, 316 Glutamate-Cysteine Ligase, 30, 286 Glutamic Acid, 28, 165, 181, 193, 283, 286, 287, 320 Glutamine, 94, 133, 140, 212, 215, 287 Glycerol, 287, 316 Glycerophospholipids, 287, 316 Glycine, 25, 86, 162, 163, 165, 166, 173, 179, 181, 193, 256, 287 Glycols, 287, 292 Glycoprotein, 17, 24, 111, 164, 280, 285, 287, 288, 302, 306, 316, 337, 341 Glycosaminoglycan, 264, 287
Glycosidic, 287 Goats, 272, 287 Gonadal, 287, 333 Gonorrhoea, 174, 287 Gout, 267, 287 Governing Board, 287, 319 Gp120, 164, 287, 314 GP41, 160, 288 Grade, 17, 288, 321 Graft, 249, 288, 291 Granule, 164, 288, 327 Granulocyte Colony-Stimulating Factor, 207, 267, 288 Granulocytes, 267, 288, 299, 330, 344 Grasses, 154, 283, 288 Gravis, 162, 288 Growth factors, 156, 171, 207, 288 Guanylate Cyclase, 46, 288, 309 H Hair Cells, 196, 197, 288 Haploid, 288, 317 Haptens, 247, 288 Hazardous Waste, 21, 288 Headache, 179, 288, 289 Headache Disorders, 288, 289 Health Policy, 40, 289 Heart attack, 261, 289 Heart failure, 49, 178, 289 Heart Transplantation, 166, 289 Hematocrit, 191, 257, 289 Hematopoiesis, 207, 289 Heme, 56, 101, 102, 256, 271, 289, 313 Hemodialysis, 90, 122, 125, 273, 289 Hemodynamics, 217, 289 Hemoglobin, 161, 250, 257, 280, 289, 297, 299 Hemoglobinuria, 230, 289 Hemorrhage, 270, 276, 288, 289, 323, 333, 343 Hemostasis, 15, 289, 329 Heparin, 165, 209, 289 Hepatic, 24, 68, 70, 90, 147, 158, 189, 202, 248, 289, 315 Hepatitis, 61, 81, 110, 138, 188, 189, 194, 202, 284, 289, 290 Hepatitis A, 81, 202, 289 Hepatocellular, 106, 110, 146, 290 Hepatocellular carcinoma, 110, 290 Hepatocyte, 46, 58, 86, 159, 290 Hepatotoxic, 82, 129, 183, 290 Hepatotoxicity, 72, 84, 147, 148, 290 Hepatovirus, 289, 290
356 Glutathione
Herbicide, 72, 187, 290 Hereditary, 43, 285, 287, 290, 308, 315, 327 Hereditary mutation, 285, 290 Heredity, 246, 285, 290 Herpes, 172, 208, 209, 290 Herpes virus, 209, 290 Herpes Zoster, 290 Heterodimer, 30, 290 Heterogeneity, 12, 19, 78, 247, 290 Heterozygotes, 63, 290 Hiccup, 264, 290 Hippocampus, 290, 308 Histamine, 156, 250, 252, 290 Histidine, 28, 290 Histocompatibility, 167, 290 Histology, 27, 290, 308, 313 Histone Deacetylase, 36, 290 Homeostasis, 5, 12, 31, 32, 41, 51, 52, 90, 291 Homogeneous, 97, 253, 291, 316 Homologous, 6, 249, 257, 285, 290, 291, 329, 335 Homozygotes, 63, 291 Hormonal, 14, 49, 153, 254, 291 Horny layer, 279, 291 Horseradish Peroxidase, 279, 291 Host, 17, 75, 155, 164, 167, 209, 249, 255, 291, 299, 319, 327, 342, 343 Housekeeping, 12, 291 Human growth hormone, 111, 291 Humoral, 182, 190, 291, 338 Humour, 291 Hybrid, 266, 291 Hybridization, 4, 291 Hybridomas, 291, 295 Hydrocortisone, 171, 291 Hydrogen Peroxide, 4, 10, 42, 47, 56, 158, 175, 261, 287, 291, 300, 334 Hydrolysis, 16, 20, 41, 92, 214, 256, 257, 265, 292, 316, 319, 322 Hydrophobic, 130, 187, 287, 292, 300 Hydroxides, 292 Hydroxy Acids, 168, 208, 292 Hydroxyl Radical, 163, 175, 292 Hydroxylysine, 267, 292 Hydroxyproline, 267, 292 Hyperbaric, 38, 292 Hyperbaric oxygen, 38, 292 Hyperbilirubinemia, 292, 297 Hyperglycemia, 40, 292 Hypersensitivity, 292, 299, 327
Hypertension, 62, 117, 173, 181, 253, 261, 277, 288, 292, 319 Hypokinesia, 292, 314 Hypotension, 181, 252, 292 Hypothermia, 203, 292 Hypoxanthine, 292, 344 Hypoxia, 42, 47, 72, 124, 126, 263, 292 I Id, 127, 136, 172, 234, 240, 242, 292 Idarubicin, 150, 192, 292 Idiopathic, 12, 105, 292, 328 Ifosfamide, 50, 192, 292 Ileitis, 162, 293 Ileum, 293 Immune function, 51, 190, 202, 293 Immune response, 72, 157, 190, 208, 251, 254, 288, 293, 334, 342, 343 Immunity, 8, 76, 114, 115, 190, 293 Immunoassay, 160, 279, 293 Immunoblotting, 62, 293 Immunocompromised, 189, 293 Immunodeficiency, 77, 88, 164, 171, 190, 230, 293 Immunogenic, 293, 300 Immunoglobulin, 251, 281, 293, 306 Immunologic, 264, 293, 324 Immunology, 85, 104, 157, 247, 283, 291, 293 Immunomodulator, 189, 293 Immunosuppressant, 249, 293 Immunosuppressive, 271, 286, 293 Immunotoxins, 293, 324 Impairment, 43, 49, 51, 72, 76, 91, 95, 203, 254, 263, 281, 293, 340 Implant radiation, 293, 296, 297, 324, 344 Implantation, 268, 293, 311, 312 Impotence, 153, 176, 280, 293, 344 In situ, 4, 6, 18, 22, 34, 48, 293 In Situ Hybridization, 4, 6, 294 Incision, 294, 296 Incompetence, 194, 294 Incontinence, 178, 294 Incubation, 56, 105, 294, 315 Incubation period, 294, 315 Indicative, 27, 211, 294, 314, 342 Indolent, 11, 294 Infarction, 41, 181, 263, 294, 326 Infection, 10, 51, 61, 68, 72, 114, 115, 120, 148, 157, 160, 171, 172, 189, 202, 207, 209, 218, 256, 264, 265, 270, 274, 281, 284, 287, 293, 294, 301, 308, 310, 314, 315, 319, 323, 327, 334, 339, 340, 344
Index 357
Infestation, 294, 302 Inflammatory bowel disease, 189, 294 Infusion, 11, 189, 218, 294 Ingestion, 5, 15, 52, 259, 288, 294, 318, 337 Inhalation, 247, 253, 254, 280, 288, 290, 294, 318, 330, 340 Initiation, 14, 28, 31, 37, 62, 78, 294, 320, 339 Inlay, 294, 326 Inner ear, 196, 197, 295 Inorganic, 112, 119, 202, 264, 265, 292, 295, 306, 309, 318 Inotropic, 275, 295 Insecticides, 133, 295, 344 Insight, 30, 33, 47, 48, 55, 59, 295 Insulator, 295, 306 Insulin, 89, 134, 137, 171, 173, 295, 298, 341 Insulin-dependent diabetes mellitus, 89, 295 Intensive Care, 51, 295 Intensive Care Units, 51, 295 Intercellular Adhesion Molecule-1, 26, 295 Interferon, 120, 140, 284, 295, 301 Interferon-alpha, 295 Interleukin-1, 88, 99, 295 Interleukin-2, 167, 295 Interleukin-6, 26, 295 Intermediate Filaments, 296, 308 Internal radiation, 296, 297, 324, 344 Interstitial, 102, 162, 258, 281, 296, 297, 344 Intestinal, 30, 70, 88, 112, 178, 181, 215, 261, 270, 278, 296, 302 Intestine, 30, 215, 256, 258, 267, 296, 298, 344 Intoxication, 179, 296, 344 Intracranial Embolism, 263, 296 Intracranial Embolism and Thrombosis, 263, 296 Intramuscular, 296, 313 Intraocular, 173, 283, 296 Intraocular pressure, 173, 283, 296 Intravenous, 11, 294, 296, 314 Intrinsic, 15, 247, 255, 296 Introns, 296, 339 Invasive, 16, 31, 40, 209, 293, 296, 302, 321 Invertebrates, 296, 339 Involuntary, 255, 279, 280, 296, 307, 331, 332 Ion Channels, 254, 296, 309, 336 Ionization, 13, 296 Ionizing, 249, 278, 296, 302, 324, 341
Ions, 15, 20, 30, 47, 150, 214, 255, 260, 275, 276, 291, 296, 305 Iris, 265, 269, 296, 323 Irradiation, 207, 258, 297, 344 Ischemia, 41, 47, 112, 124, 126, 147, 180, 191, 254, 259, 297, 326 Isocyanates, 60, 297 Isoenzyme, 34, 79, 98, 146, 211, 270, 297 Isoleucine, 202, 297 Isothiocyanates, 39, 88, 297 Isozymes, 18, 24, 32, 33, 34, 66, 72, 75, 132, 206, 297 J Jaundice, 174, 292, 297 Joint, 14, 297, 335, 336 K Kallidin, 258, 297 Kava, 82, 129, 297 Kb, 158, 224, 297 Keratin, 297, 328 Keratinocytes, 86, 115, 297 Keto, 9, 297 Ketone Bodies, 245, 298 Kidney Cortex, 298, 304 Kidney Disease, 224, 231, 298 Kidney Transplantation, 191, 298 Killer Cells, 298 Kinetic, 14, 15, 35, 51, 66, 67, 158, 214, 296, 298 L Labile, 48, 267, 298 Labyrinth, 266, 295, 298, 329, 343 Lac Operon, 205, 298 Lactate Dehydrogenase, 29, 298 Lactation, 267, 298, 311 Large cell carcinomas, 27, 298 Large Intestine, 267, 274, 296, 298, 324, 331, 344 Laryngeal, 107, 298 Larynx, 286, 298, 339 Laser therapy, 168, 298 Latency, 209, 298 Latent, 164, 298, 319 Lavage, 5, 299 Laxative, 248, 299, 331 Least-Squares Analysis, 299, 325 Lens, 18, 38, 106, 253, 261, 299 Lesion, 13, 57, 172, 299, 301 Lethal, 6, 73, 255, 274, 299, 306 Leucine, 202, 299 Leucocyte, 249, 299, 301 Leukaemia, 99, 107, 299
358 Glutathione
Leukemia, 4, 19, 38, 75, 93, 95, 230, 275, 299 Leukocytes, 257, 258, 264, 288, 295, 299, 315, 341 Leukotrienes, 253, 299 Levo, 299, 303 Library Services, 240, 299 Life cycle, 209, 284, 299 Ligament, 299, 321 Ligands, 299, 335 Ligase, 28, 299 Ligation, 167, 299 Likelihood Functions, 299, 325 Linear Models, 300, 325 Linkage, 27, 198, 285, 300 Lipase, 41, 300 Lipid A, 16, 300 Lipid Bilayers, 45, 300 Lipid Peroxides, 158, 300 Lipoamide Dehydrogenase, 78, 300 Lipopolysaccharide, 85, 174, 300 Lipoprotein, 202, 300, 301, 343 Lipoxygenase, 87, 253, 299, 300 Liver cancer, 61, 202, 300 Liver Transplantation, 81, 300 Lobe, 263, 291, 300 Localization, 6, 16, 36, 47, 58, 69, 73, 301 Localized, 86, 153, 245, 259, 274, 277, 282, 294, 301, 317 Locomotion, 301, 317 Logistic Models, 301, 325 Low-density lipoprotein, 181, 300, 301 Lubricants, 301, 316 Lubrication, 153, 301 Lupus, 301, 336 Lymph, 17, 164, 172, 187, 190, 255, 263, 278, 291, 301, 328, 334 Lymph node, 17, 164, 172, 255, 263, 301, 328 Lymphatic, 278, 294, 301, 304, 331, 332 Lymphatic system, 301, 331, 332 Lymphoblastic, 99, 107, 301 Lymphoblasts, 34, 246, 301 Lymphocyte, 120, 157, 251, 298, 301, 303 Lymphoid, 251, 270, 299, 301 Lymphoma, 11, 137, 230, 301 Lymphoproliferative, 11, 301 Lymphoproliferative Disorders, 11, 301 Lysine, 150, 208, 292, 302 Lytic, 188, 302, 329 M Macrophage, 57, 76, 115, 207, 267, 295, 302
Macrophage Colony-Stimulating Factor, 207, 267, 302 Macula, 283, 302 Macula Lutea, 302 Macular Degeneration, 173, 175, 302 Magnetic Resonance Imaging, 39, 302 Malabsorption, 230, 302 Malignancy, 207, 302 Malignant tumor, 160, 302, 306 Malnutrition, 130, 248, 254, 259, 302, 306 Malondialdehyde, 4, 42, 53, 89, 105, 117, 118, 132, 133, 302, 337 Mammary, 17, 267, 302 Mange, 171, 172, 302 Manifest, 170, 200, 302 Man-made, 261, 302 Matrix metalloproteinase, 117, 302 Meat, 204, 273, 302 Meat Products, 204, 273, 302 Medial, 253, 302, 311 Mediate, 23, 26, 46, 59, 275, 298, 303 Mediator, 91, 295, 303, 329 MEDLINE, 225, 228, 231, 303 Medulloblastoma, 19, 303 Megakaryocytes, 258, 303, 338 Megaloblastic, 283, 303 Meiosis, 257, 303, 304, 335, 341 Melanin, 297, 303, 316, 341 Melanocytes, 82, 303 Melanoma, 38, 230, 258, 303 Melanosomes, 303 Melphalan, 192, 303 Memory, 181, 251, 272, 303 Meninges, 263, 270, 303 Meningitis, 287, 303 Menopause, 153, 176, 303, 311 Menorrhagia, 174, 303 Menstrual Cycle, 109, 182, 303, 311, 320 Menstruation, 272, 303 Mental Health, iv, 4, 101, 224, 227, 303, 322 Mercury, 22, 41, 107, 123, 126, 134, 184, 283, 304 Mesencephalic, 61, 304, 325 Mesenchymal, 279, 302, 304 Metabolite, 28, 34, 257, 304, 320 Metallothionein, 77, 174, 175, 304 Metaphase, 257, 304, 341 Metaplasia, 81, 304 Metastasis, 17, 160, 302, 304 Metastatic, 195, 304, 328 Methamphetamine, 20, 304
Index 359
Methionine, 58, 162, 304, 334 Methyltransferase, 49, 113, 304 MI, 17, 206, 243, 304 Microbe, 304, 339 Microbiology, 109, 122, 124, 246, 304 Micromanipulation, 16, 304 Micromanipulators, 304 Micronuclei, 89, 304 Microorganism, 266, 304, 314, 343 Microscopy, 15, 23, 38, 255, 291, 305 Microsomal, 35, 71, 83, 84, 91, 103, 107, 146, 202, 229, 305 Microtubule-Associated Proteins, 305, 308 Microtubules, 296, 305, 308, 313 Migration, 295, 305 Milk Thistle, 141, 142, 305, 330 Milligram, 157, 305 Mitochondria, 12, 29, 30, 42, 43, 56, 57, 68, 76, 117, 124, 126, 305, 312, 339 Mitochondrial Swelling, 305, 307 Mitosis, 252, 304, 305 Mobility, 16, 305 Modeling, 33, 67, 73, 107, 305 Modification, 33, 38, 41, 43, 73, 147, 173, 206, 285, 305, 323 Modulator, 55, 195, 305 Molecular mass, 158, 305 Molecular Structure, 35, 305 Monitor, 13, 15, 39, 191, 270, 305, 310 Monoclonal, 24, 160, 185, 291, 293, 297, 306, 324, 344 Monoclonal antibodies, 24, 160, 185, 293, 306 Monocyte, 57, 302, 306 Mononuclear, 302, 306, 341 Morphological, 23, 248, 277, 303, 306 Morphology, 38, 261, 306 Motion Sickness, 306, 307 Mucins, 306, 328 Mucolytic, 245, 306 Mucosa, 215, 278, 301, 306, 333 Mucus, 257, 306, 341 Multidrug resistance, 24, 84, 116, 130, 306, 316 Multiple Myeloma, 11, 92, 110, 117, 123, 124, 125, 126, 306 Multiple sclerosis, 108, 162, 306 Muscle Fibers, 306, 307, 340 Muscular Atrophy, 230, 306 Muscular Dystrophies, 276, 306 Musculoskeletal System, 270, 306 Mustard Gas, 306, 307
Mutagen, 92, 307 Mutagenesis, 29, 33, 35, 44, 59, 156, 213, 307 Mutagenic, 28, 34, 35, 54, 66, 73, 156, 249, 307, 310, 341 Mutagenicity, 28, 156, 307 Myasthenia, 162, 307 Mycotoxins, 61, 247, 307 Mydriatic, 274, 307, 344 Myelin, 306, 307 Myeloma, 117, 124, 126, 307 Myocardial infarction, 40, 62, 89, 106, 132, 162, 181, 269, 304, 307 Myocarditis, 274, 307 Myocardium, 50, 304, 307, 327 Myosin, 147, 307, 340 Myotonic Dystrophy, 230, 307 Myristate, 114, 307 N Narcotic, 245, 307, 310 Natural killer cells, 167, 307 Natural selection, 256, 307 Nausea, 179, 251, 252, 275, 284, 307, 336 NCI, 1, 223, 265, 307 Necrosis, 29, 190, 252, 259, 263, 280, 286, 294, 304, 307, 326, 328 Nematocide, 280, 308 Neocortex, 308 Neonatal, 47, 51, 96, 287, 308 Neoplasia, 20, 31, 230, 308, 321 Neoplasm, 93, 193, 308, 328, 341 Neoplastic, 193, 250, 291, 301, 308 Nephropathy, 131, 180, 298, 308 Neural, 124, 126, 250, 291, 308 Neuroblastoma, 85, 108, 308 Neurodegenerative Diseases, 6, 13, 173, 255, 308 Neurofibrillary Tangles, 9, 308 Neurofilaments, 308 Neurologic, 286, 308 Neurology, 33, 42, 47, 61, 99, 163, 308 Neuronal, 9, 41, 58, 135, 163, 308 Neurons, 9, 41, 42, 55, 58, 61, 86, 163, 196, 197, 272, 281, 284, 308, 309, 335 Neuropathy, 131, 308 Neuropeptide, 164, 308 Neurophysiology, 273, 309 Neurotoxic, 12, 245, 309 Neurotoxicity, 41, 309 Neurotransmitters, 16, 163, 309 Neutrons, 249, 258, 297, 309, 324 Neutropenia, 207, 309
360 Glutathione
Neutrophil, 295, 309 Nicardipine, 309 Nicotine, 151, 205, 309 Nimustine, 113, 309 Nitric Oxide, 40, 42, 46, 47, 73, 74, 88, 101, 104, 105, 117, 123, 125, 152, 174, 178, 191, 309 Nitrogen, 10, 31, 154, 155, 175, 176, 180, 205, 248, 249, 271, 281, 282, 287, 303, 305, 309, 310, 340 Nitrogen Compounds, 155, 309 Nitroglycerin, 165, 310 Nitrosamines, 205, 310 Nitrous Oxide, 44, 310 Non-small cell lung cancer, 24, 84, 111, 310 Norepinephrine, 247, 275, 310, 326 Nosocomial, 8, 310 Nuclei, 12, 249, 268, 276, 281, 285, 296, 302, 304, 305, 309, 310, 311, 322, 336 Nucleic acid, 155, 158, 186, 188, 193, 260, 271, 285, 291, 292, 294, 309, 310, 323 Nucleic Acid Hybridization, 291, 310 Nutritional Status, 157, 310 O Occupational Exposure, 100, 310 Ocular, 18, 310 Oculomotor, 304, 310 Odour, 253, 310 Oestrogen, 205, 310 Ointments, 275, 311, 313, 331 Oltipraz, 61, 311 Oncogene, 230, 311 Oncogenic, 170, 200, 311, 319, 322 Oncogenic Viruses, 311, 319 Oncologist, 5, 311 Oophoritis, 287, 311 Opacity, 261, 272, 311 Ophthalmology, 38, 106, 116, 282, 311 Opsin, 311, 326 Optic Chiasm, 311 Optic Disk, 273, 302, 311 Optic Nerve, 173, 311, 326, 327, 328 Optic nerve head, 173, 311 Organ Culture, 311, 338 Organ Preservation, 166, 203, 311, 312 Organ Preservation Solutions, 166, 312 Organelles, 16, 29, 263, 271, 303, 312, 318 Orgasm, 153, 276, 312 Osmotic, 248, 305, 312, 330 Osteoporosis, 311, 312 Ototoxic, 23, 312
Outpatient, 312 Ovaries, 281, 312, 326, 330 Ovary, 41, 311, 312, 318, 333 Overdose, 199, 284, 312 Overexpress, 11, 42, 312 Ovum, 272, 285, 299, 312, 320, 344, 345 Oxaliplatin, 192, 312 Oxidants, 18, 55, 59, 162, 168, 169, 199, 312 Oxidation-Reduction, 257, 312 Oxidative metabolism, 247, 299, 312 Oxidative Stress, 3, 6, 7, 8, 9, 10, 12, 13, 14, 18, 22, 25, 26, 29, 30, 36, 37, 38, 41, 42, 43, 46, 47, 49, 51, 53, 55, 56, 58, 59, 61, 63, 64, 65, 68, 72, 85, 86, 89, 100, 112, 134, 135, 147, 175, 185, 196, 197, 199, 206, 209, 218, 313 Oxides, 109, 287, 313 Oxygen Consumption, 214, 313, 326 Oxygenase, 101, 313 P Paclitaxel, 24, 110, 134, 141, 313 Palliative, 311, 313, 337 Palpitation, 176, 313 Pancreas, 245, 257, 295, 300, 313, 329, 341 Pancreatic, 64, 103, 138, 230, 261, 279, 313 Pancreatic cancer, 230, 279, 313 Papilla, 94, 313 Papillary, 97, 313 Papovaviridae, 313, 319 Paraffin, 193, 313 Paralysis, 245, 304, 313 Parasite, 68, 97, 313 Parathyroid, 171, 313, 337 Parathyroid Glands, 313 Parathyroid hormone, 171, 313 Parenteral, 195, 313 Parkinsonism, 22, 252, 314 Parotid, 314, 328 Paroxysmal, 230, 254, 289, 314, 315, 344 Partial remission, 314, 325 Particle, 302, 314, 339 Patch, 62, 314 Pathogen, 67, 172, 294, 314 Pathogenesis, 4, 37, 41, 42, 49, 61, 172, 314 Pathologic, 168, 192, 252, 269, 292, 314, 322 Pathologic Processes, 252, 314 Pathologies, 109, 176, 314 Pathophysiology, 5, 49, 314 Pelvic, 153, 278, 314, 321 Penicillin, 251, 314 Penis, 153, 276, 314, 316, 326 Pepsin, 314, 329
Index 361
Peptide, 45, 64, 158, 169, 170, 198, 200, 205, 206, 282, 284, 297, 314, 319, 321, 322 Peptide T, 198, 314 Perennial, 154, 314, 340 Perforation, 314, 344 Perfusion, 159, 173, 191, 257, 292, 314 Pericardium, 314, 336 Perinatal, 47, 314 Periodontal disease, 196, 315 Periodontitis, 162, 315 Peripheral Nervous System, 278, 308, 315, 334 Peripheral Vascular Disease, 181, 315 Peritoneal, 187, 254, 315 Peritoneal Cavity, 254, 315 Peritoneum, 315 Peritonitis, 287, 315, 344 Peroxidase, 7, 9, 10, 18, 23, 26, 38, 40, 42, 47, 49, 50, 53, 54, 56, 58, 63, 64, 68, 72, 73, 74, 76, 79, 81, 87, 91, 92, 93, 96, 97, 102, 106, 109, 112, 113, 115, 119, 122, 123, 124, 126, 129, 130, 133, 134, 135, 148, 154, 156, 158, 163, 174, 188, 197, 214, 217, 218, 228, 229, 253, 287, 300, 315, 329 Peroxide, 10, 30, 38, 47, 61, 102, 105, 122, 124, 256, 315 Peroxisome Proliferators, 14, 315 Pertussis, 75, 315, 344 Petroleum, 284, 313, 315 P-Glycoprotein, 16, 316 Phagocyte, 302, 312, 316 Phallic, 282, 316 Pharmaceutical Solutions, 275, 316 Pharmacokinetic, 17, 23, 51, 201, 316 Pharmacologic, 36, 53, 62, 250, 316, 339 Pharynx, 151, 177, 316 Phenobarbital, 24, 316 Phenotype, 6, 17, 22, 30, 36, 78, 171, 193, 256, 268, 316 Phenyl, 112, 316 Phenylalanine, 79, 202, 316, 341 Phorbol, 114, 316 Phospholipases, 316, 330 Phospholipids, 118, 282, 300, 316 Phosphorous, 154, 316 Phosphorus, 155, 260, 313, 316 Phosphorylate, 40, 316 Phosphorylated, 266, 316 Phosphorylation, 31, 56, 66, 89, 91, 131, 167, 170, 195, 316 Photocoagulation, 266, 316
Photodynamic therapy, 16, 317 Photosensitivity, 16, 317 Phototherapy, 117, 317 Phylogeny, 77, 317 Physical Examination, 161, 317 Physiologic, 24, 36, 40, 193, 208, 248, 257, 292, 303, 317, 321, 324, 340 Physiology, 30, 40, 55, 62, 86, 94, 110, 117, 160, 215, 256, 277, 309, 317 Pigment, 175, 256, 264, 303, 317, 327 Pilot study, 11, 317 Pituitary Gland, 282, 283, 317 Placenta, 78, 100, 123, 125, 158, 283, 317, 320 Plana, 317, 330 Plaque, 37, 181, 250, 317 Plasma, 16, 23, 26, 36, 42, 74, 94, 96, 102, 106, 107, 109, 118, 130, 132, 148, 158, 187, 192, 218, 248, 251, 258, 262, 264, 267, 278, 285, 286, 289, 306, 307, 317, 325, 329, 330 Plasma cells, 251, 306, 307, 317 Plasma protein, 248, 278, 317, 330 Plasmid, 48, 317, 342 Plastic surgeon, 168, 317 Plastids, 312, 318 Platelet Activation, 318, 330 Platelet Aggregation, 250, 283, 309, 318, 338 Platelets, 42, 104, 178, 207, 253, 309, 318, 337, 338 Platinum, 23, 26, 90, 110, 134, 192, 193, 265, 312, 318 Platinum Compounds, 27, 312, 318 Pneumoconiosis, 318, 330 Poisoning, 259, 260, 276, 284, 296, 304, 307, 318 Pollen, 318, 323 Polyarthritis, 150, 318 Polycystic, 231, 318 Polyethylene, 73, 318 Polymerase, 10, 66, 318, 320 Polymers, 318, 322, 334 Polymorphic, 30, 33, 167, 318 Polymorphism, 3, 44, 50, 75, 82, 83, 93, 98, 106, 110, 114, 318 Polyomavirus, 120, 313, 319 Polypeptide, 68, 158, 185, 249, 260, 267, 279, 291, 319, 321, 345 Polyposis, 43, 267, 319 Polysaccharide, 251, 263, 287, 319
362 Glutathione
Posterior, 173, 250, 254, 263, 265, 275, 296, 313, 319, 328 Postnatal, 20, 319, 333 Postsynaptic, 319, 330, 335, 336 Post-translational, 50, 56, 59, 147, 148, 319 Post-traumatic, 94, 289, 319 Potassium, 71, 155, 165, 181, 191, 319, 331 Potentiate, 105, 123, 125, 207, 319 Potentiation, 111, 164, 319, 330 Practicability, 319, 340 Practice Guidelines, 227, 319 Precancerous, 264, 319 Preclinical, 32, 209, 319 Predisposition, 58, 319 Pre-Eclampsia, 96, 106, 118, 319 Premalignant, 319, 321 Prenatal, 47, 277, 320 Presynaptic, 320, 335 Preventive Medicine, 30, 239, 320 Prickle, 297, 320 Primary tumor, 195, 320 Primitive neuroectodermal tumors, 303, 320 Probe, 44, 117, 320 Prodrug, 37, 90, 201, 206, 320 Progeny, 268, 320 Progesterone, 320, 333 Prognostic factor, 320, 335 Progression, 19, 31, 39, 50, 57, 111, 189, 251, 320, 341 Progressive, 176, 253, 262, 265, 272, 275, 276, 288, 306, 307, 308, 318, 320, 341 Projection, 272, 310, 311, 320, 325 Proline, 118, 205, 267, 292, 320 Promoter, 9, 19, 24, 36, 82, 167, 320, 324 Promotor, 320, 326 Promyelocytic leukemia, 11, 320, 340 Prophase, 257, 320, 335, 341 Prophylaxis, 188, 320, 342 Proportional, 20, 277, 279, 320, 335 Prospective study, 5, 27, 320 Prostaglandin, 58, 71, 83, 84, 86, 321, 338 Prostaglandins A, 321 Prostate, 36, 83, 85, 89, 90, 97, 99, 102, 133, 151, 178, 230, 257, 311, 321, 326, 341 Prostatic Intraepithelial Neoplasia, 36, 321 Protease, 46, 185, 205, 250, 267, 321 Protective Devices, 198, 321 Protein C, 33, 68, 187, 188, 198, 248, 249, 252, 255, 266, 282, 297, 300, 321, 340, 341, 343 Protein Conformation, 249, 297, 321
Protein Kinases, 31, 59, 78, 321 Protein S, 25, 55, 163, 193, 214, 231, 257, 274, 280, 285, 291, 321, 322, 327, 337 Protein Subunits, 25, 55, 322 Proteinuria, 306, 319, 322 Proteolytic, 249, 267, 322 Protons, 249, 291, 296, 322, 324 Proto-Oncogene Proteins, 313, 322 Proto-Oncogene Proteins c-mos, 313, 322 Protozoa, 268, 305, 322, 332, 340 Protozoal, 322, 340 Proximal, 60, 153, 275, 298, 320, 322 Pruritic, 172, 276, 322 Pruritus, 172, 174, 322 Psoriasis, 306, 322, 340 Psychiatric, 256, 322 Psychiatry, 83, 282, 322 Psychic, 322, 329 Public Health, 8, 10, 26, 27, 28, 61, 151, 153, 177, 227, 322 Public Policy, 225, 322 Publishing, 63, 322 Pulmonary, 8, 12, 15, 27, 51, 90, 258, 264, 269, 299, 323, 326, 335, 343 Pulmonary Artery, 258, 323, 343 Pulmonary Edema, 264, 323 Pulmonary Ventilation, 323, 326 Pulse, 16, 305, 323 Pupil, 265, 269, 274, 307, 323 Purifying, 53, 185, 198, 323 Purines, 323, 344 Purpura, 105, 323 Purulent, 287, 323 Pustular, 208, 246, 323 Pyruvate Dehydrogenase Complex, 300, 323 Q Quality of Life, 323, 334 Quercetin, 104, 209, 323 Quiescent, 30, 323 Quinone Reductases, 59, 323 Quinones, 49, 323 R Rabies, 4, 323 Race, 303, 305, 324 Radiation oncologist, 311, 324 Radiation therapy, 54, 281, 283, 292, 296, 297, 324, 344 Radioactive, 291, 293, 296, 297, 302, 306, 310, 311, 324, 341, 344 Radiolabeled, 258, 297, 324, 344 Radiopharmaceutical, 285, 324
Index 363
Radiotherapy, 258, 297, 309, 324, 344 Randomized, 205, 276, 324 Reactive Oxygen Species, 4, 7, 9, 10, 15, 25, 43, 49, 52, 56, 58, 59, 61, 169, 172, 175, 324 Reagent, 191, 264, 275, 280, 324 Recombinant, 69, 76, 77, 84, 114, 115, 158, 164, 171, 186, 187, 198, 205, 257, 324, 342 Recombinant Fusion Proteins, 186, 324 Recombinant Proteins, 187, 198, 324 Recombination, 268, 285, 324 Rectum, 110, 252, 267, 274, 283, 284, 294, 298, 321, 324 Recur, 172, 325 Recurrence, 17, 209, 264, 325 Red blood cells, 89, 102, 167, 280, 313, 325, 328 Red Nucleus, 254, 325 Refer, 1, 267, 275, 282, 284, 290, 301, 302, 309, 310, 325, 343 Refraction, 325, 332 Refractory, 11, 21, 92, 117, 123, 124, 125, 126, 276, 325 Regeneration, 175, 194, 282, 325 Regimen, 5, 15, 193, 276, 325 Regression Analysis, 51, 325 Regulon, 70, 325 Relapse, 218, 325 Relaxant, 283, 325 Remission, 11, 325 Renal Artery, 191, 325 Renal cell cancer, 100, 325 Renin, 260, 325 Renin-Angiotensin System, 260, 325 Reperfusion, 41, 147, 191, 326 Reperfusion Injury, 147, 326 Reproductive cells, 285, 290, 326 Reproductive system, 214, 326 Reserpine, 309, 326 Respiration, 29, 43, 260, 305, 326 Respiratory distress syndrome, 51, 326 Respiratory System, 28, 326 Response Elements, 7, 9, 59, 326 Restoration, 24, 191, 326, 344 Resuscitation, 103, 326 Retina, 265, 268, 273, 299, 302, 311, 326, 327, 330 Retinal, 175, 273, 311, 326, 327 Retinal Ganglion Cells, 311, 327 Retinal pigment epithelium, 175, 327 Retinoblastoma, 230, 327 Retinoid, 208, 327
Retinol, 326, 327 Retrospective, 27, 84, 327 Retrovirus, 164, 327 Reversion, 201, 327, 341 Rheumatic Heart Disease, 181, 327 Rheumatism, 83, 190, 327 Rheumatoid, 103, 106, 138, 150, 189, 267, 312, 327 Rheumatoid arthritis, 103, 106, 189, 267, 327 Ribose, 87, 246, 327 Ribosome, 327, 339 Rigidity, 314, 317, 327 Risk factor, 3, 5, 8, 17, 27, 39, 49, 97, 181, 279, 301, 320, 327 Rod, 255, 265, 327 Rotenone, 62, 327 Rutin, 323, 327 S Salicylate, 327 Salicylic, 208, 328 Salicylic Acids, 328 Saliva, 187, 328 Salivary, 313, 328, 334 Salivary glands, 328 Salpingitis, 287, 328 Saponins, 328, 333 Sarcoidosis, 189, 328 Sarcoma, 320, 328, 331 Schizoid, 328, 344 Schizophrenia, 83, 328, 344 Schizotypal Personality Disorder, 328, 344 Sclera, 265, 269, 328 Sclerosis, 83, 117, 230, 253, 267, 306, 328 Screening, 6, 51, 54, 115, 158, 163, 195, 198, 205, 266, 328 Sebum, 246, 328 Second Messenger Systems, 309, 328 Secondary tumor, 304, 328 Secretin, 206, 329 Secretion, 5, 21, 25, 75, 105, 246, 279, 290, 291, 295, 298, 306, 328, 329 Secretory, 321, 329, 335 Sedative, 297, 329 Segregation, 28, 324, 329 Seizures, 123, 126, 286, 314, 329 Selenocysteine, 62, 79, 158, 329 Semen, 187, 276, 321, 329 Semicircular canal, 295, 329 Seminiferous tubule, 329, 332 Semisynthetic, 122, 124, 260, 293, 329 Senescence, 7, 65, 76, 329
364 Glutathione
Senile, 18, 312, 329 Sepsis, 5, 15, 46, 51, 52, 329 Septic, 44, 46, 329 Sequence Homology, 67, 314, 329 Sequencing, 22, 42, 329 Serologic, 293, 329 Serotonin, 252, 278, 326, 329, 340 Serous, 267, 278, 330 Serrata, 139, 265, 330 Serrated, 330 Serum, 112, 116, 118, 129, 171, 186, 187, 192, 202, 248, 250, 267, 270, 301, 315, 329, 330, 341 Serum Albumin, 171, 330 Sex Characteristics, 247, 311, 330, 337 Sex Determination, 231, 330 Shock, 12, 44, 46, 291, 330, 340 Side effect, 23, 60, 199, 207, 247, 252, 256, 271, 275, 330, 334, 339 Signal Transduction, 44, 55, 78, 101, 167, 170, 200, 211, 330 Signs and Symptoms, 151, 177, 325, 330 Silicon, 155, 330 Silicon Dioxide, 330 Silicosis, 162, 330 Silymarin, 196, 305, 330 Skeletal, 65, 102, 167, 265, 270, 306, 331, 332, 340 Skeleton, 246, 297, 321, 331 Skin Aging, 169, 331 Skull, 270, 331, 336 Small cell lung cancer, 331 Small intestine, 215, 265, 276, 291, 293, 296, 331 Smooth muscle, 37, 178, 249, 250, 269, 283, 290, 310, 326, 331, 332, 334 Sneezing, 315, 331 Soaps, 201, 331 Sodium, 78, 118, 166, 209, 287, 331 Soft tissue, 4, 258, 331 Soft tissue sarcoma, 4, 331 Solid tumor, 4, 23, 24, 32, 250, 275, 331 Solvent, 182, 245, 280, 287, 312, 316, 331, 340 Soma, 331 Somatic, 59, 247, 291, 303, 305, 315, 331 Sorbitol, 77, 331 Spasm, 290, 304, 332, 337 Spasmodic, 315, 332 Spatial disorientation, 275, 332 Specialist, 235, 274, 332
Specificity, 33, 34, 48, 76, 146, 195, 198, 247, 248, 253, 332 Spectrophotometry, 23, 332 Spectrum, 20, 24, 271, 332, 341 Sperm, 113, 265, 285, 290, 318, 326, 329, 332 Spermatozoa, 94, 109, 329, 332 Spinal cord, 164, 254, 259, 263, 264, 303, 308, 315, 332 Spinous, 279, 297, 332 Spleen, 301, 328, 332 Sporadic, 33, 72, 110, 308, 327, 332 Spores, 176, 332 Squamous, 27, 84, 93, 279, 310, 332 Squamous cell carcinoma, 84, 93, 279, 310, 332 Squamous cells, 332 Stabilizer, 166, 332 Staurosporine, 85, 333 Steady state, 14, 160, 333 Steel, 265, 333 Stellate, 24, 333 Stem Cells, 63, 164, 280, 333 Sterile, 313, 333 Sterility, 94, 271, 333 Steroid, 49, 145, 158, 211, 256, 270, 286, 310, 328, 333 Stimulant, 20, 205, 273, 290, 297, 304, 333 Stimulus, 89, 131, 269, 276, 281, 296, 298, 333, 337 Stomach, 101, 138, 166, 179, 245, 274, 280, 284, 285, 291, 299, 307, 314, 315, 316, 329, 331, 332, 333, 344 Stool, 294, 298, 333 Strand, 10, 38, 48, 318, 333 Stria, 23, 333 Stria Vascularis, 23, 333 Stroke, 40, 96, 162, 180, 181, 224, 261, 333 Stromal, 99, 258, 278, 333 Stromal Cells, 258, 333 Structure-Activity Relationship, 324, 333 Styrene, 89, 104, 334 Subacute, 294, 334 Subarachnoid, 288, 334 Subclinical, 294, 329, 334 Subcutaneous, 276, 313, 334 Submaxillary, 279, 334 Subspecies, 332, 334 Substance P, 280, 304, 329, 334 Substrate, 13, 29, 32, 34, 37, 48, 60, 67, 75, 117, 119, 155, 186, 211, 213, 261, 277, 279, 334
Index 365
Substrate Specificity, 29, 32, 67, 213, 334 Sulfur, 16, 34, 66, 69, 124, 126, 127, 178, 180, 194, 196, 201, 208, 281, 287, 304, 334 Sunburn, 168, 169, 334 Supplementation, 8, 30, 89, 115, 129, 130, 132, 134, 135, 146, 218, 334 Supportive care, 207, 334 Suppression, 65, 77, 207, 285, 334 Suppressive, 189, 334 Suppurative, 287, 334 Suramin, 24, 334 Surface Plasmon Resonance, 186, 334 Surfactant, 5, 51, 65, 280, 335 Survival Analysis, 27, 335 Survival Rate, 26, 335 Suspensions, 17, 335 Sympathomimetic, 273, 275, 279, 304, 310, 335 Symphysis, 321, 335 Symptomatic, 209, 335 Synapses, 309, 335 Synapsis, 335 Synaptic, 72, 164, 309, 330, 335 Synaptic Membranes, 164, 335 Synaptic Transmission, 72, 309, 335 Synergistic, 48, 135, 151, 171, 172, 177, 336 Synovial, 103, 336 Synovial Fluid, 103, 336 Synovial Membrane, 336 Systemic lupus erythematosus, 98, 162, 267, 336 Systolic, 50, 292, 336 Systolic heart failure, 50, 336 T Taurine, 171, 256, 336 Technology Transfer, 22, 336 Telangiectasia, 231, 336 Telencephalon, 255, 336 Tellurium, 16, 336 Telophase, 304, 336 Temporal, 21, 42, 289, 290, 302, 336 Tendinitis, 162, 336 Teratogenic, 249, 336, 340 Terminator, 266, 337 Testis, 311, 337 Testosterone, 7, 69, 176, 325, 337 Tetany, 313, 337 Tetracycline, 56, 275, 337 Thalamic, 254, 337 Thalamic Diseases, 254, 337 Therapeutics, 5, 32, 88, 90, 107, 114, 116, 131, 158, 171, 337
Thermal, 66, 168, 172, 253, 258, 275, 309, 337 Thiobarbituric Acid Reactive Substances, 52, 337 Thioguanine, 147, 337 Thioredoxin, 46, 71, 76, 78, 81, 94, 113, 115, 118, 135, 160, 205, 211, 337 Threonine, 314, 322, 337 Threshold, 44, 193, 292, 337 Thrombin, 282, 318, 321, 337 Thrombocytes, 318, 337 Thrombocytopenia, 207, 337 Thrombomodulin, 321, 337 Thrombopoietin, 207, 338 Thrombosis, 181, 191, 296, 322, 333, 338 Thromboxanes, 253, 338 Thrombus, 178, 269, 294, 318, 338 Thymidine, 338 Thymidylate Synthase, 54, 338 Thyroid, 97, 99, 101, 118, 313, 338, 341 Thyroid Gland, 313, 338 Thyroxine, 248, 316, 338 Tin, 318, 338 Tissue Culture, 11, 58, 63, 187, 338, 343 Tissue Extracts, 40, 338 Tissue Preservation, 165, 338 Tolerance, 70, 74, 85, 154, 187, 246, 286, 338 Tooth Preparation, 246, 338 Topical, 168, 169, 172, 195, 208, 254, 280, 291, 313, 331, 338, 340 Torsion, 294, 338 Toxins, 9, 23, 33, 45, 172, 194, 251, 286, 293, 294, 306, 307, 324, 339 Toxoplasmosis, 255, 339 Trace element, 54, 175, 258, 265, 330, 338, 339 Trachea, 259, 298, 316, 338, 339 Traction, 265, 339 Transcriptase, 164, 174, 218, 327, 339 Transcription Factors, 7, 25, 46, 326, 339 Transduction, 156, 167, 170, 200, 330, 339 Transfection, 38, 56, 59, 257, 339 Transferases, 3, 13, 18, 23, 25, 32, 34, 35, 36, 59, 61, 66, 67, 69, 72, 74, 76, 84, 92, 93, 94, 100, 101, 107, 112, 115, 117, 130, 133, 145, 146, 147, 148, 155, 184, 209, 211, 212, 213, 214, 339 Translation, 6, 280, 324, 339 Translational, 5, 8, 285, 339 Translocation, 47, 280, 339
366 Glutathione
Transmitter, 245, 254, 275, 296, 303, 310, 335, 339 Transplantation, 50, 81, 92, 159, 165, 166, 171, 191, 203, 265, 339 Trans-Splicing, 81, 339 Trauma, 10, 52, 162, 202, 307, 340 Treatment Outcome, 26, 340 Trees, 22, 44, 74, 340 Tremor, 304, 314, 340 Tretinoin, 91, 340 Trichloroethylene, 22, 340 Trichome, 69, 340 Trifluoperazine, 309, 340 Troglitazone, 103, 340 Trophic, 9, 196, 340 Tropomyosin, 340 Troponin, 50, 340 Trypan Blue, 185, 340 Trypanosomiasis, 334, 340 Tryptophan, 267, 329, 340 Tuberculosis, 80, 269, 301, 328, 340 Tuberous Sclerosis, 231, 340 Tumor marker, 21, 257, 340 Tumor model, 5, 17, 341 Tumor Necrosis Factor, 26, 49, 226, 341 Tumorigenic, 21, 341 Tumour, 71, 111, 341 Tunicamycin, 9, 341 Type 2 diabetes, 91, 94, 341 Typhimurium, 68, 70, 72, 341 Tyrosine, 56, 62, 73, 91, 119, 135, 167, 170, 208, 275, 341 U Ubiquitin, 308, 341 Ulcerative colitis, 190, 294, 341 Ultraviolet Rays, 168, 169, 341 Unconscious, 272, 292, 341 Univalent, 292, 312, 341 Unresectable, 111, 341 Urea, 215, 341 Ureters, 325, 341 Urethra, 314, 321, 341, 342 Urethritis, 287, 342 Uric, 249, 287, 323, 342 Urinary, 92, 178, 271, 285, 294, 341, 342, 344 Urine, 39, 42, 187, 257, 267, 270, 275, 279, 285, 286, 289, 294, 298, 322, 325, 341, 342 Urogenital, 174, 285, 342 Uterus, 153, 263, 270, 272, 278, 281, 303, 312, 320, 326, 342
V Vaccination, 4, 184, 342 Vaccine, 4, 66, 342 Vacuole, 69, 342 Vagina, 153, 264, 273, 274, 303, 326, 342 Vaginal, 153, 187, 301, 342 Valves, 327, 342 Vascular, 26, 37, 40, 103, 178, 181, 184, 190, 191, 249, 263, 265, 278, 289, 294, 309, 317, 333, 338, 342 Vascular endothelial growth factor, 103, 342 Vascular Resistance, 191, 342 Vasculitis, 162, 263, 342 Vasoactive, 105, 342 Vasoconstriction, 173, 279, 342 Vasodilation, 40, 153, 342 Vasodilator, 259, 275, 290, 309, 342 Vasogenic, 41, 342 Vector, 28, 63, 154, 167, 339, 342 Vegetative, 154, 342 Vein, 105, 250, 253, 296, 310, 314, 342 Venous, 153, 253, 257, 259, 263, 296, 310, 322, 342 Ventral, 61, 310, 343 Ventricle, 62, 290, 323, 336, 343 Ventricular, 49, 62, 343 Venules, 258, 260, 278, 343 Verapamil, 309, 343 Vertebrae, 332, 343 Vesicular, 290, 305, 343 Vestibular, 196, 197, 288, 343 Vestibule, 266, 295, 329, 343 Veterinary Medicine, 172, 225, 343 Vimentin, 156, 157, 343 Vinca Alkaloids, 343 Vincristine, 150, 343 Vinorelbine, 150, 343 Viral, 10, 138, 164, 185, 209, 245, 260, 285, 288, 311, 323, 327, 339, 341, 343 Virion, 209, 343 Virulence, 76, 254, 339, 343 Viscera, 331, 343 Viscosity, 245, 343 Vitreous Hemorrhage, 273, 343 Vitro, 5, 9, 10, 11, 12, 16, 25, 28, 37, 41, 47, 48, 49, 54, 58, 60, 61, 70, 71, 73, 89, 92, 104, 118, 147, 170, 171, 183, 200, 226, 289, 294, 338, 343 Vivo, 5, 8, 10, 11, 12, 17, 25, 28, 36, 37, 39, 41, 47, 49, 56, 57, 58, 60, 62, 78, 87, 109,
Index 367
130, 134, 147, 170, 171, 183, 200, 206, 289, 294, 300, 312, 338, 344 Volvulus, 76, 344 W White blood cell, 26, 246, 251, 267, 299, 301, 302, 306, 307, 309, 317, 344 Whooping Cough, 315, 344 Windpipe, 316, 338, 344 Withdrawal, 9, 344 Womb, 326, 342, 344 Wound Healing, 282, 302, 344 X Xanthine, 197, 249, 344 Xanthine Oxidase, 197, 249, 344
Xenobiotics, 13, 14, 25, 32, 34, 55, 67, 147, 344 Xenograft, 251, 341, 344 X-ray, 13, 33, 35, 38, 45, 262, 283, 284, 297, 302, 307, 310, 324, 332, 341, 344 X-ray therapy, 297, 344 Y Yeasts, 284, 316, 344 Yohimbine, 153, 344 Z Zoonoses, 323, 345 Zygote, 268, 345 Zymogen, 321, 345
368 Glutathione
