CHONDROITIN A M EDICAL D ICTIONARY , B IBLIOGRAPHY , AND A NNOTATED R ESEARCH G UIDE TO I NTERNET R E FERENCES
J AMES N. P ARKER , M.D. AND P HILIP M. P ARKER , P H .D., E DITORS
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ICON Health Publications ICON Group International, Inc. 4370 La Jolla Village Drive, 4th Floor San Diego, CA 92122 USA Copyright 2003 by ICON Group International, Inc. Copyright 2003 by ICON Group International, Inc. All rights reserved. This book is protected by copyright. No part of it may be reproduced, stored in a retrieval system, or transmitted in any form or by any means, electronic, mechanical, photocopying, recording, or otherwise, without written permission from the publisher. Printed in the United States of America. Last digit indicates print number: 10 9 8 7 6 4 5 3 2 1
Publisher, Health Care: Philip Parker, Ph.D. Editor(s): James Parker, M.D., Philip Parker, Ph.D. Publisher's note: The ideas, procedures, and suggestions contained in this book are not intended for the diagnosis or treatment of a health problem. As new medical or scientific information becomes available from academic and clinical research, recommended treatments and drug therapies may undergo changes. The authors, editors, and publisher have attempted to make the information in this book up to date and accurate in accord with accepted standards at the time of publication. The authors, editors, and publisher are not responsible for errors or omissions or for consequences from application of the book, and make no warranty, expressed or implied, in regard to the contents of this book. Any practice described in this book should be applied by the reader in accordance with professional standards of care used in regard to the unique circumstances that may apply in each situation. The reader is advised to always check product information (package inserts) for changes and new information regarding dosage and contraindications before prescribing any drug or pharmacological product. Caution is especially urged when using new or infrequently ordered drugs, herbal remedies, vitamins and supplements, alternative therapies, complementary therapies and medicines, and integrative medical treatments. Cataloging-in-Publication Data Parker, James N., 1961Parker, Philip M., 1960Chondroitin: 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: 0-597-83867-4 1. Chondroitin-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 chondroitin. 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 CHONDROITIN .......................................................................................... 3 Overview........................................................................................................................................ 3 The Combined Health Information Database................................................................................. 3 Federally Funded Research on Chondroitin................................................................................... 4 E-Journals: PubMed Central ....................................................................................................... 61 The National Library of Medicine: PubMed ................................................................................ 64 CHAPTER 2. NUTRITION AND CHONDROITIN .............................................................................. 111 Overview.................................................................................................................................... 111 Finding Nutrition Studies on Chondroitin................................................................................ 111 Federal Resources on Nutrition ................................................................................................. 119 Additional Web Resources ......................................................................................................... 120 CHAPTER 3. ALTERNATIVE MEDICINE AND CHONDROITIN ........................................................ 123 Overview.................................................................................................................................... 123 The Combined Health Information Database............................................................................. 123 National Center for Complementary and Alternative Medicine................................................ 124 Additional Web Resources ......................................................................................................... 133 General References ..................................................................................................................... 135 CHAPTER 4. DISSERTATIONS ON CHONDROITIN .......................................................................... 137 Overview.................................................................................................................................... 137 Dissertations on Chondroitin..................................................................................................... 137 Keeping Current ........................................................................................................................ 138 CHAPTER 5. CLINICAL TRIALS AND CHONDROITIN ..................................................................... 139 Overview.................................................................................................................................... 139 Recent Trials on Chondroitin..................................................................................................... 139 Keeping Current on Clinical Trials ........................................................................................... 140 CHAPTER 6. PATENTS ON CHONDROITIN ..................................................................................... 143 Overview.................................................................................................................................... 143 Patents on Chondroitin.............................................................................................................. 143 Patent Applications on Chondroitin .......................................................................................... 172 Keeping Current ........................................................................................................................ 199 CHAPTER 7. BOOKS ON CHONDROITIN ........................................................................................ 201 Overview.................................................................................................................................... 201 Book Summaries: Online Booksellers......................................................................................... 201 Chapters on Chondroitin............................................................................................................ 202 CHAPTER 8. PERIODICALS AND NEWS ON CHONDROITIN ........................................................... 205 Overview.................................................................................................................................... 205 News Services and Press Releases.............................................................................................. 205 Newsletters on Chondroitin ....................................................................................................... 207 Newsletter Articles .................................................................................................................... 207 Academic Periodicals covering Chondroitin .............................................................................. 210 APPENDIX A. PHYSICIAN RESOURCES .......................................................................................... 213 Overview.................................................................................................................................... 213 NIH Guidelines.......................................................................................................................... 213 NIH Databases........................................................................................................................... 215 Other Commercial Databases..................................................................................................... 218 The Genome Project and Chondroitin........................................................................................ 218 APPENDIX B. PATIENT RESOURCES ............................................................................................... 223 Overview.................................................................................................................................... 223 Patient Guideline Sources.......................................................................................................... 223 Finding Associations.................................................................................................................. 226
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APPENDIX C. FINDING MEDICAL LIBRARIES ................................................................................ 229 Overview.................................................................................................................................... 229 Preparation................................................................................................................................. 229 Finding a Local Medical Library................................................................................................ 229 Medical Libraries in the U.S. and Canada ................................................................................. 229 ONLINE GLOSSARIES................................................................................................................ 235 Online Dictionary Directories ................................................................................................... 235 CHONDROITIN DICTIONARY ................................................................................................ 237 INDEX .............................................................................................................................................. 327
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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 chondroitin 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 chondroitin, 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 chondroitin, 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 chondroitin. 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 chondroitin, 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 chondroitin. 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 CHONDROITIN Overview In this chapter, we will show you how to locate peer-reviewed references and studies on chondroitin.
The Combined Health Information Database The Combined Health Information Database summarizes studies across numerous federal agencies. To limit your investigation to research studies and chondroitin, 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 “chondroitin” (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: •
Determining the Efficacy of Glucosamine and Chondroitin for Osteoarthritis Source: Nurse Practitioner, The. 26(6): 44-46,49-52. June 2001. Summary: This journal article provides health professionals with information on the use of glucosamine and chondroitin in the treatment of osteoarthritis (OA). Although OA was once regarded as a simple consequence of aging and cartilage degeneration, researchers now believe that OA may be a group of overlapping diseases rather than a single disorder. The functional properties of articular cartilage are the core of OA pathogenesis. Components of articular cartilage are water, collagen, proteoglycans, chondrocytes, and other matrix components. Over time, the catabolism of proteoglycans and the increased loss of glycosaminoglycans result in the abrasion of cartilage and the formation of new bone within the joint. In healthy people, a balance of cartilage matrix turnover is maintained through synthesis and degradation. The failure to maintain this
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homeostatic balance because of reduced formation or increased catabolism is a possible explanation for OA. Treatment modalities focus on primary and secondary prevention. Primary prevention involves educating patients about joint protection, exercise, weight reduction, and the dangers of repetitive motion. Secondary prevention is mainly palliative and involves both nonpharmacologic and pharmacologic therapies to minimize pain. Glucosamine sulfate and chondroitin sulfate are being used by many patients for the treatment of OA. The article reviews human and animal studies on the use of these agents in treating OA. Despite findings in many of these studies supporting the efficacy of these agents for palliation of joint pain in patients with OA, the American College of Rheumatology Subcommittee on OA believes that it is too early to issue recommendations for use. Currently, the National Institute for Arthritis and Musculoskeletal and Skin Diseases, in collaboration with the National Center for Complementary and Alternative Medicine has begun a pivotal study to thoroughly evaluate these agents. 36 references. (AA-M). •
Glucosamine and Chondroitin Source: Arthritis Today. 12(5): 46-48,51. September-October 1998. Summary: This journal article provides people who have arthritis with information on the dietary supplements glucosamine and chondroitin. Both glucosamine and chondroitin are substances found in the body and needed in the metabolism of cartilage. The supplements have been lauded as cures for osteoarthritis (OA). There is increasing evidence that they actually relieve the pain of OA in some people. Results from more than a dozen European studies on humans reveal that about half of the participants with mild to moderate OA who took either of the supplements reported some pain relief. Although more research is needed, there is even some evidence that the supplements may slow down loss of cartilage. Despite this evidence, most researchers and doctors, even those who are using the supplements themselves, are wary of the hype and commercialism surrounding them. There is no quality control of glucosamine and chondroitin products because they are sold as dietary supplements and are therefore not regulated by the Food and Drug Administration. Only long-term, scientifically controlled studies will prove the effectiveness and safety of these supplements. People who decide to try them should consult their doctor first, continue to take their prescription medications unless their doctor tells them to stop, be sure that OA is the cause of their pain, avoid the supplements if they are pregnant or could become pregnant, check their blood sugar levels frequently if they have diabetes, check their blood-clotting time frequently if they are taking a blood-thinning medication or daily aspirin and chondroitin, and continue proven pain management techniques.
Federally Funded Research on Chondroitin The U.S. Government supports a variety of research studies relating to chondroitin. 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. 2
Healthcare projects are funded by the National Institutes of Health (NIH), Substance Abuse and Mental Health Services (SAMHSA), Health Resources and Services Administration (HRSA), Food and Drug Administration (FDA), Centers for Disease Control and Prevention (CDCP), Agency for Healthcare Research and Quality (AHRQ), and Office of Assistant Secretary of Health (OASH).
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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 chondroitin. 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 chondroitin. The following is typical of the type of information found when searching the CRISP database for chondroitin: •
Project Title: A BIOMIMETIC BARRIER FOR ISLET IMMUNOISOLATION Principal Investigator & Institution: Chaikof, Elliot L.; J.E. Skandalakis Professor; Medicine; Emory University 1784 North Decatur Road Atlanta, Ga 30322 Timing: Fiscal Year 2001; Project Start 30-SEP-1999; Project End 31-AUG-2003 Summary: Enhanced control of both transport properties and surface physiochemical characteristics will be important steps in the development of an effective immunoisolation barrier critical to the success of pancreatic islet cell transplantation. In this proposal, we hypothesize that the cell membrane establishes an important paradigm for the design of a biomimetic immunoisolation barrier with improved performance characteristics because of its capacity to control interfacial mass transport, as well as through its ability to act as a template for more complex structures with other immunoregulatory macromolecules. Specifically, we intend to: 1) Synthesize and characterize a membrane-mimetic, glycosaminoglycan (GAG) containing, glycocalyx for limiting complement activation and macrophage adhesion in the presence of encapsulated xenogeneic islets. In order to limit both complement activation and macrophage adhesion, heparan and chondroitin sulfate will be used as pendant groups on polymerizable phospholipid macromolecules. Alginate-supported lipid membrane assemblies will be produced, polymerized in situ, and both physiochemical and biological properties defined in vitro. 2) Define the transport characteristics of dendrimer based molecular channels. Poly(ethylene oxide) (PEO) dendrimers with macromolecular generations will be synthesized, end-functionalized with a polymerizable moiety, and stably inserted into membrane-mimetic films as artificial transmembrane channels. Diffusivity and mass transfer coefficients will be determined for a range of molecules of varying size and chemical composition. Encapsulated islet cell viability and glucose responsiveness will be defined in vitro. 3) Characterize the physiochemical properties of a biomimetic barrier which influence islet xenograft survival in vivo. Survivability of donor pancreatic islet grafts will be defined in a NOD mouse model using well characterized isograft and xenograft (Porcine yields NOD) models of islet transplantation. Critical endpoints will include capsule stability and biocompatibility, graft survival, and maintenance of euglycemia. The development of an inflammatory response will be analyzed at both cellular and molecular levels utilizing immunohistochemistry, FACS, and PCR based techniques. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen
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Project Title: ADAPTATION OF NEURONS TO INHIBITORY EXTRACELLULAR MATRIX Principal Investigator & Institution: Condic, Maureen L.; Neurobiology and Anatomy; University of Utah 200 S University St Salt Lake City, Ut 84112 Timing: Fiscal Year 2001; Project Start 01-JAN-1999; Project End 31-DEC-2002
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Summary: The adult central nervous system (CNS) does not readily support axonal regeneration following injury. In contrast, there is extensive regeneration and functional recovery in embryos following CNS damage. The inability of the adult CNS to regenerate appears to be due both to changes in the extracellular environment of the nervous system that did make it less permissive to neuronal growth and to changes in the intrinsic ability of adult neurons to regenerate damage axons. By the end of embryonic development, the expressions of growth-promoting or stimulatory extracellular matrix molecules in the CNS is quite low. Myelin-associated factors found in mature brain tissue actively inhibit axonal growth and following injury, several additional inhibitory proteins are up-regulated in regions of scarring. Compounds these less than ideal extracellular conditions, the regeneration of adult neurons is somehow compromised by changes associated with neuronal maturation. Recent work has shown that embryonic neurons readily adapt both to low availability of growth promoting molecules and to the presence of inhibitory compounds by regulating the expression of integrins--the receptors extracellular matrix proteins that mediate axon extension. The compensatory regulation of integrin by components of the matrix has not been previous described for any cell type, may contribute to the superior regenerative performance of embryonic neurons under less than ideal extracellular conditions. Integrins are known to interact with both extracellular and cytoskeletal proteins. In Aim 1, the contributions of ligand and cytoskeletal binding to the regulation of integrin expression will be examined using antibodies, pharmacological reagents and integrin mutant constructs. The contribution of integrin regulation to the adaptation of embryonic neurons to inhibitory matrix components will be characterized in Aim 2. Neuronal response to members of two major inhibitory families that are expressed in the CNS following injury will be determined. The role of one inhibitory proteoglycan (aggrecan) in neuronal development will be examined using mutant animals that do not express aggrecan. Experiments proposed in Aims 3 and 4 will determine whether increased integrin expression is sufficient to mediate neuronal adaptation to both low availability of ligand and to inhibitory molecules (conditions similar to those in the adult CNS following injury). Integrin expression will be increased in both embryonic and adult neurons using replication- deficient adenoviral constructs. The performance of neurons with increased integrin expression will be examined on substrata that would otherwise not support neuronal growth. In summary, these experiments will greatly strengthen our understanding of two novel forms of integrin regulation, and potentially provide a basis for improving the regenerative performance of adult neurons. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •
Project Title: AGGRECAN FOLDING, CHAPERONES, AND INTRACELLULAR ROUTING Principal Investigator & Institution: Tanzer, Marvin L.; Professor and Head; Biostructure and Function; University of Connecticut Sch of Med/Dnt Bb20, Mc 2806 Farmington, Ct 060302806 Timing: Fiscal Year 2001; Project Start 01-APR-1999; Project End 31-MAR-2003 Summary: Aggrecan imparts resilience to articular cartilage, enabling cartilage to withstand compression, thereby protecting the bony surfaces of joints. Aggrecan's protective properties emanate from its molecular structure which is assembled via a complicated cellular pathway. A critical element early in that pathway is quality control, imposed by molecular chaperones which assist aggrecan core protein to properly fold before it can continue on its route. Until now, the molecular chaperones responsible for assisting aggrecan core protein to fold have not been identified; recent studies in this lab
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have implicated chaperone Hsp25 as a principal participant in that process. It is postulated that Hsp25 binds to the nascent core protein's G3 domain in the cytosol and accompanies the core protein into the lumen of the endoplasmic reticulum where it assists G3 folding; once folded, G3, as an intramolecular chaperone, binds to the core protein's nascent G1 domain, releasing Hsp25 which recycles to the cytosol; G3, while adhering to G1, enters the Golgi zones where glycosaminoglycan chains are added, followed by secretion of completed aggrecan into the matrix. The long term objective of this proposal is to comprehend the molecular details of this proposed aggrecanchaperone pathway; critical features of Hsp25-G3 association and dissociation will be investigated, including diversion of Hsp25/G3 complexes into the nucleus and culture medium under certain circumstances. Three specific aims will focus on: 1) which amino acids in nascent G3 interact with Hsp25 and vice-versa; 2) the nature of the interactions of G1, G3 and Hsp25; 3) which isoform(s) of Hsp25 interact with G3. Cellular transfection with informative constructs will be used to explore each specific aim; normal and mutant Hsp25 and G3 proteins will be expressed, as will hybrid proteins formed between G1, G3, Hsp25 and unique colored isoforms of green fluorescent protein (GFP). GFP labeling will enable tracking of expressed proteins through intracellular compartments; simultaneous tracking of two different proteins will be accomplished as they will be emitting separate colors. Other studies will utilize expressed G1, G3 and Hsp25 proteins containing a polyhistidine tag; proteins will be labeled using radioactive precursors, then harvested and purified by immunocapture and/or by nickel chelation. The composite results will further define a unique system for aggrecan core protein folding and routing. Cartilage repair, including aggrecan production, is impaired in arthritic disease. Understanding the chaperone-based pathway of aggrecan formation and its regulation will potentially provide new insights into the way in which arthritic diseases alter cartilage physiology. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •
Project Title: BASEMENT MEMBRANE PROTEOGLYCANS Principal Investigator & Institution: Couchman, John R.; Professor; Cell Biology; University of Alabama at Birmingham Uab Station Birmingham, Al 35294 Timing: Fiscal Year 2001; Project Start 30-SEP-1985; Project End 30-NOV-2003 Summary: Basement membranes are sheets of extracellular matrix with the potential to influence tissue and cell behavior. They can serve as an adhesion scaffolds, regulate permeability, and influence migration, development and differentiation. Basement membrane composition includes collagens, glycoproteins and proteoglycans. Bamacan is a chondroitin sulfate proteoglycan that may regulate basement membrane stability since its expression is low in developing tissue and disrupted in skin and other organs in diseases where matrix integrity is compromised, e.g. dystrophic epidermolysis bullosa. Bamacan core protein has an unusual five domain head-rod-tail structure, not seen in any other matrix component, consistent with a distinct, but as yet unknown, role in matrix biology. The long term objective of this research is to understand its function in normal and diseased tissues. Molecular, immunochemical and cell culture studies are proposed that target: 1) the structure and organization of bamacan core protein. Protein sequence predicts that the rod domains form coiled-coil alpha helices, with stabilization through dimer formation. A partner protein for bamacan will be identified and characterized. Intermolecular interactions between head and tail domains in homologous or heterologous assemblies will be elucidated. Further proposed experiments examine the sites and role of bamacan's chondroitin sulfate chain substitution. 2) the hypothesis that bamacan influences basement membrane stability.
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Cell culture systems will be used to examine whether the presence of bamacan affects the rate of matrix turnover. Three different methodologies, incorporating regulated bamacan expression and its glycanation are proposed. 3) bamacan core protein and carbohydrate expression in patients with epidermolysis bullosa and the effects of bamacan on key features of cell behavior including adhesion, cytoskeletal organization and migration. 4) the molecular properties of human bamacn, and the regulation of expresson by keratinocytes. The epidermal compartment is the source of dermalepidermal junction bamacan in vivo, but this is not matched in vitro, perhaps as seen in disease. Roles for regulation by matrix and growth factors will be assessed. Genomic cloning of mouse bamacan is proposed, with emphasis on the 5' regions, directed towards understanding gene regulation as well as future targeted deletion. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •
Project Title: BIOBEHAVIORAL RESEARCH CENTER(BRC) Principal Investigator & Institution: Yucha, Carolyn B.; Professor and Associate Dean for Researc; Adult and Elderly Nursing; University of Florida Gainesville, Fl 32611 Timing: Fiscal Year 2001; Project Start 01-AUG-2001; Project End 31-JUL-2004 Summary: (from applicant's Abstract) The goal of the Biobehavioral Research Center (BRC) in the University of Florida College of Nursing is to provide the infrastructure for faculty to develop state-of-the-art interdisciplinary research that integrates biological and behavioral sciences. The long-term goal of the BRC is to advance our understanding of biobehavioral aspects of health promotion, disease prevention, and nursing interventions for acute and chronic illness across the lifespan. The specific aims of the BRC are: (1) Develop a cadre of nurse scientists with expertise in the integration of biological and behavioral sciences, (2) Develop programs of Biobehavioral research that promote health, prevent disease and improve nursing care, and, (3) Disseminate research findings that interpret biological and behavioral sciences to impact nursing care. These aims will be supported by the Administrative and Pilot Cores, which will work together to provide fiscal oversight; allocation of shared resources including space, equipment and statistical consultation; provision of educational programs and mentoring opportunities, and, patient safety oversight. Five biobehavioral pilot studies are proposed: (1) GlutenFree & Casein-Free Dietary Treatment in Autism, (2) Exercise, Bone Density & Balance in Postmenopausal Women, (3) Effect of Immune Mediators on Quality of Life in Allergy, (4) Promoting Adherence: Theory-based Asthma Education, and (5) Managing OA Symptoms: Glucosamine and Chondroitin Sulfate. The CON is positioned to rapidly expand its research mission and profile. The BRC will facilitate this growth by augmenting the current research support infrastructure and enhancing the development of interdisciplinary collaboration in the Health Science Center and the University at large. The BRC is supported by the extensive resources and environment at the University of Florida and by substantial financial support provided by the University and the College of Nursing. At the end of three years, at least twelve nurse scientists with expertise in biobehavioral research will be developed, and a minimum of ten pilot studies will be funded, half of which will develop into programs of biobehavioral research leading to greater extramural funding. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen
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Project Title: BIOLOGICAL BASIS OF MENTAL RETARDATION Principal Investigator & Institution: Schwartz, Nancy B.; Professor; Pediatrics; University of Chicago 5801 S Ellis Ave Chicago, Il 60637
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Timing: Fiscal Year 2001; Project Start 01-JUN-1975; Project End 31-DEC-2003 Summary: The unifying goal of this program project proposal is to define the principles governing normal nervous system developmental processes that may lead to brain dysfunction and mental retardation. The studies for the most part are basic in nature, focusing on various aspects of the cell and its environment that are involved in overall developmental processes; including examination of the extracellular matrix (ECM), cell membrane gap junctions, cytoskeletal proliferation. The derivative information from these proposed studies should define specific loci where normal developmental processes. The first project focuses on the structure and function of brain proteoglycans. The emphasis is on control of one of the major chondroitin sulfate proteoglycans (aggrecan) and elucidation of the role this important ECM component plays in neuronal development. The second project will examine intracellular communication which may play a significant role in embryonic neural development by specifically studying Connexin45, a subunit gap junction protein with special permeability properties. The third project focuses on function of NF1 protein in central nervous system neurons and astrocytes using a combination of biochemical, molecular biology and confocal microscopy techniques in tissue culture models from the chick embryos and human CNS cell lines. The fourth project is aimed toward understanding the pathogenesis of Batten disease. The aim is to develop diagnostic biochemical assays for the enzymes deficient in CLN2 (PPT) and CLN2 (endoprotease) and to determine the cause of neuronal death. A comprehensive multi-disciplinary approach using biochemical, molecular, morphologic and cell culture techniques will be used in all four projects. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •
Project Title: BIOLOGICAL ROLE OF ADAMTS PROTEASES Principal Investigator & Institution: Apte, Suneel; Associate Staff Scientist; Cleveland Clinic Foundation 9500 Euclid Ave Cleveland, Oh 44195 Timing: Fiscal Year 2003; Project Start 01-APR-2003; Project End 31-MAR-2008 Summary: (provided by applicant): ADAMTS proteases have important functions such as processing of procollagen (ADAMTS-2, -3 and -14), large aggregating proteoglycans (ADAMTS-4, -5, -1), and von Willebrand factor (ADAMTS-13), with corresponding roles in disorders such as dermatosparaxis, arthritis, brain tumor invasion and idiopathic thrombocytopenic purpura. However, the biological function of most ADAMTS proteases is not known. ADAMTS-9 and ADAMTS-20, two enzymes we have discovered, are the largest of all ADAMTS enzymes. They have a unique domain structure similar to that of the C.elegans GON-1 enzyme that is essential for cell migration during gonadal morphogenesis. ADAMTS-20 is now known to have a role in neural crest cell migration, but the function of ADAMTS-9 is not known. Preliminary studies show that ADAMTS-9 has a unique temporal and spatial expression pattern in mesoderm and its derivatives during mouse development. We have found that this is the first family member to be localized to the cell surface, although it does not have a transmembrane domain. Furthermore, ADAMTS-9 transfected cells can cut a similar site in cartilage aggrecan as ADAMTS-4, suggesting that ADAMTS-9 is a cell surface aggrecanase. We report that ADAMTS-9 is present in rheumatoid synovium. These findings lead to the hypothesis that proteolysis of aggrecan, and related proteoglycans such as versican and brevican, by ADAMTS-9 is crucial to completion of normal development, as well as to diseases such as arthritis. The ancillary domains of ADAMTS-9 may play a substantial role in substrate recognition and targeting to the cell surface. The Specific Aims are to determine the physiological function of ADAMTS-9, characterize its activity against aggrecan and other substrates, and to determine the
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basis for such activity and for cell surface localization. In doing so, we anticipate comparing ADAMTS-9 to ADAMTS-20, as well as other relevant ADAMTS enzymes. These aims will be addressed by generation of ADAMTS-9 null mice, structure-function analysis, and analysis of potential substrates biochemically and in situ. The significance of these studies lies in improved fundamental understanding of proteolysis during development and human disease, especially arthritis. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •
Project Title: BIOLOGY OF BAMACAN IN TUMORIGENESIS Principal Investigator & Institution: Ghiselli, Giancarlo; Pathology, Anat/Cell Biology; Thomas Jefferson University Office of Research Administration Philadelphia, Pa 191075587 Timing: Fiscal Year 2001; Project Start 01-FEB-2001; Project End 31-JAN-2005 Summary: Colon cancer is one of the leading causes of mortality in western countries. Whereas much progress has been made to date, in a significant number of cases the molecular mechanisms underlying the initiation of the disease and its progression remain unknown. Bamacan is a newly described chondroitin sulfate proteoglycan that abounds in basement membranes and is also found in the cell nucleus. The applicant recently cloned and characterized the bamacan gene and found that its expression is significantly increased in approx. 70 percent of human colon carcinomas. Aberrant bamacan was also detected in five human colon carcinoma cell lines and in neoplastic tissue of APC Min/+ mice that lack a functional APC tumor suppressor and develop intestinal tumors. Overexpression of bamacan in normal fibroblasts causes transformation, including formation of foci, acquisition of anchorage independent growth and loss of contact inhibition. Bamacan belongs to the Structural Maintenance of Chromosome (SMC) family of proteins and is involved in DNA repair and in the ordered separation of sister chromatids. Alteration of these processes leads to genetic instability and aneuploidy, conditions that can initiate the tumorigenic process. A hypothesis of the proposal is that deregulated expression of bamacan is either initiating transformation or is a secondary event that is necessary for the clonal propagation of the neoplastic cells. A long-term research objective is to elucidate the role of bamacan in the establishment and maintenance of a transformed phenotype. This revised grant proposes to investigate: 1) The transcriptional regulation of the bamacan gene. 2) The functional role of bamacan in tumorigenesis by altering its expression and by assessing the effect of protein mutation using a dominant-negative approach. 3) The contribution of bamacan in vivo to colon tumorigenesis by generating transgenic mice overexpressing bamacan in the intestinal epithelium. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen
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Project Title: CELL SURFACE MOLECULES OF THE DEVELOPING NERVOUS SYSTEM Principal Investigator & Institution: Levine, Joel M.; Professor; Neurobiology and Behavior; State University New York Stony Brook Stony Brook, Ny 11794 Timing: Fiscal Year 2001; Project Start 01-JUL-1984; Project End 30-JUN-2004 Summary: Oligodendrocytes the myelin forming cells of the CNS, develop from an identified precursor cell (OPC). OPCs are abundant in developing and adult animals suggesting that these cells carry out functions in addition to providing a pool of oligodendrocyte precursors. OPCs express on their surfaces NG2 a chondroitin sulfate proteoglycan that can inhibit axonal growth and guide axon elongation in vitro. The
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expression of NG2 is maximal during development and again when the brain suffers an injury. This suggests that OPCs can provide negative, growth inhibitory cues to both developing and regenerating axons and that NG2 is the biochemical basis for this contact mediated growth inhibition. The goal of this proposal is to test this hypothesis of OPC function. Under Specific Aim 1 the complete distribution of OPCs and NG2 in the developing CNS will be mapped and compared to the distribution of newly formed axon tracts and to other putative growth inhibitory molecules. This data will provide the anatomical framework against which to evaluate the hypothesis that OPCs define areas that are non-permissive for axon growth during early CNS development. Under Specific Aim 2 the membrane properties of OPCs will be directly evaluated using a in vitro membrane carpet assays. Fusion proteins that encode small regions of NG2 will be prepared and tested for their ability to inhibit axonal outgrowth and neutralizing monoclonal antibodies prepared against those domains of NG2 that are active in these assays. Knock-in cell lines will be created that express these growth inhibitory domains and the ability of these lines to inhibit axon growth evaluated. Time-lapse video microscopy will be used in Specific Aim 3 to determine whether the induction of growth cone collapse is a mechanism by which OPCs inhibit axonal growth. In Specific Aim 4 the ability of membranes prepared from CNS scar tissue to promote or inhibit axonal outgrowth will be tested and the role of NG2 in any inhibition evaluated using the domain specific neutralizing anti-NG2 antibodies. This aim also includes a detailed biochemical analysis of the temporal patterns of expression of growth promoting and growth inhibiting molecules after injury. The proposed studies will provide important information concerning the functions of a newly recognized class of glial cells during development, tissue repair and regeneration. They will also provide information concerning the functions of proteoglycans in the CNS. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •
Project Title: CHONDROCYTE TRANSDUCTION
DEFORMATION
AND
MECHANICAL
Principal Investigator & Institution: Guilak, Farshid; Associate Professor; Surgery; Duke University Durham, Nc 27706 Timing: Fiscal Year 2001; Project Start 01-AUG-1997; Project End 31-JUL-2003 Summary: The mechanical environment of the chondrocytes is one of the most important factors affecting the health and function of the diarthrodial joint. Under normal physiologic conditions, chondrocytes utilize mechanical signals in conjunction with genetic and biochemical factors to maintain the articular cartilage extracellular matrix. However, abnormal loading conditions such as excessive stresses or alterations in joint loading are believed to be significant factors in the initiation and progression, of joint disease. The sequence of mechanical and biochemical events regulating these signal transduction processes in vivo are still unclear, although indirect evidence suggests that cellular deformation serves as a primary regulatory signal. The central hypothesis of this project is that cyclic deformation of the chondrocytes regulates the transduction of mechanical loads to a biochemical response through two pathways: the actin cytoskeleton and the calcium ion (Ca2+) second messenger system. It is hypothesized that deformation of the cytoskeleton and the chondrocyte nucleus are responsible for regulating changes in proteoglycan synthesis rates, while deformation-induced ca2+ waves regulate the expression of the chondroitin sulfate 3-B-3(-) epitope, considered to be a marker of early osteoarthritis. The goals of the proposed project will be accomplished using a bovine articular cartilage explant model loaded in pure torsion. This loading configuration differs from all previously used systems in that it will result
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Chondroitin
in purely deviatoric deformation within the explant (i.e., deformation without volume changes), allowing isolation of the effects of cell and tissue deformation from those of most other physical factors (e.g., fluid flow, fluid and osmotic pressures, streaming potentials, etc.). The following specific aims will be performed: l) Quantify the relationship between the magnitude, duration and frequency of cyclic torsion on proteoglycan synthesis rates and 3-B-3(-) expression using autoradiography and immunolocalization; 2) Determine the role of the actin cytoskeleton in mechanical transduction using chemical agents which disrupt actin microfilaments; 3) Determine the role of deformation-induced Ca2+ waves in mechanical transduction using inhibitors of Ca2+ mobilization. The long term goals of this study are to determine the roles of mechanical factors in regulating cartilage metabolism under normal or abnormal conditions and to identify the signal transduction pathways. A better understanding of these pathways will lead to the development of pharmaceutical or biophysical interventions for the treatment of osteoarthritis. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •
Project Title: CHONDROITIN LOCALIZATION
SULFATE
BIOSYNTHESIS
CELLULAR
Principal Investigator & Institution: Sugumaran, Geetha; Biochemistry; Boston University Medical Campus 715 Albany St, 560 Boston, Ma 02118 Timing: Fiscal Year 2001; Project Start 01-MAY-1993; Project End 31-MAR-2003 Summary: Proteochondroitin sulfate is a major structural constituent of connective tissue, and occurs as an ubiquitous component of cell surface, where it is considered to be involved in specific cell-cell, cell-matrix and cell-receptor functions. Changes in metabolism of proteochondroitin sulfate are thought to impact upon multiple diseases and conditions involving connective tissue such as arthritis, atherosclerosis, improper wound healing etc. Knowledge of the biosynthetic regulation will assist in understanding how the metabolism and fine structure of this molecule relates to the pathology of many conditions. The polysaccharide portion of the molecule is frequently the "business end", with the core protein portion involved in channeling the molecule to the appropriate cellular locations. Thus, the size of the chondroitin chains and the degree and type of sulfation provide much of the specificities in function. The control in synthesis of this fine structure is directly related to the specificity of the chondroitin sulfate initiating enzymes, membrane topography at the sites of synthesis and to the concerted interaction of all the biosynthetic enzymes. Knowledge of the structure and characteristics of the individual enzymes is essential to understand this membrane organization. Thus, the following specific aims will be pursued: Aim I. We will purify and characterize the specific enzymes involved in the addition of the first glucuronic acid and first N- acetylgalactosamine residues to the linkage trisaccharide that is attached to the core protein. The acceptor specificities of these enzymes will be determined. Aim II. The interaction of these enzymes with each other and with the chondroitin-polymerizing glucuronosyl transferase and N- acetylgalactosamine transferase will be investigated. In addition, the interaction of all these enzymes with nascent proteochondroitin will be examined. Aim III. We will clone and express the cDNA for the chondroitin- polymerizin glucuronosyl transferase that we have purified. These studies will provide fundamental information for examining the regulation and organization of proteochondroitin synthesis and will enable us to obtain necessary tools for future studies. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen
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Project Title: CHONDROITIN SULFATE GAG INHIBITION OF GROWTH CONES Principal Investigator & Institution: Bellamkonda, Ravi V.; Associate Professor; Biomedical Engineering; Case Western Reserve University 10900 Euclid Ave Cleveland, Oh 44106 Timing: Fiscal Year 2003; Project Start 01-DEC-2002; Project End 31-AUG-2003 Summary: (provided by applicant): Regenerative failure in the central nervous system (CNS) is a significant clinical problem. Regenerative failure is thought to occur due to the formation of astroglial scar at the site of injury , which in turn blocks regenerating or sprouting neurons. The molecular composition of glial scar, particularly the presence of chondroitin sulfate proteoglycans (CSPGs), is responsible for inhibition of growth cones and regenerative failure. However, the mechanism by which CSPGs inhibit growth cones is not known. Recent successes in various in vivo CNS injury models in eliciting regeneration by digesting the glycosaminoglycan (GAG) portion of CSPGs using chondroitinase ABC suggests that the GAGs present on CSPGs may contribute significantly to CSPG-mediated inhibition. Our central hypotheses are: i) the CS-GAG component of CSPGs contribute significantly to the inhibition of peripheral (PNS) and CNS growth cones; and that ii) this inhibition is mediated by signaling mechanisms involving an increase in intracellular calcium and a decrease in cAMP levels. The purpose of Aim 1 of this proposal is to characterize the upregulation of CS-GAGs in response to injury of the adult mammalian CNS using a very sensitive and novel technique (FACE). Additionally, Aim l introduces innovative techniques to present the upregulated CS-GAGs to growth cones in a controlled fashion to investigate the direct inhibition of growth cones by CS-GAGs. The purpose of Aim 2 of this proposal is to investigate the signaling mechanism(s) by which CS-GAGs cause growth cone inhibition, focusing specifically on growth cone concentrations of calcium and cAMP and how their levels change when growth cones contact CS-GAGs. To achieve our goals, we use novel and innovative methods to achieve high spatial control over the immobilization of CSGAGs onto glass cover slips using a micro-fluidics approach. We also use CS-GAGs coupled to Dynal beads to present CSGAGs to growth cones and study the growth cone dynamics in response to contact with inhibitory CS-GAGs. Our methods assume significance because we show that immobilized CS-GAGs are inhibitory whereas soluble GAGs are not, and it is imperative to control the manner in which CS-GAGs are presented to growth cones. This is not surprising given that in vivo, at the site of injury, growth cones encounter CS-GAGs immobilized in the scar matrix. When successfully completed, our research will clarify the extent and mechanism(s) of CS-GAG mediated inhibition of growth cones, and the potential contribution that the GAG components of CSPGs make to CNS inhibition at astroglial scars. With such elucidation, strategies will be developed to alleviate CS-GAG mediated inhibition, assisting growth cones to grow through CS-GAG/CSPG rich areas, facilitating regeneration. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen
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Project Title: CHONDROITIN DEVELOPMENT
SULFATE
PROTEOGLYCANS
IN
LUNG
Principal Investigator & Institution: Shannon, John M.; Associate Professor; Children's Hospital Med Ctr (Cincinnati) 3333 Burnet Ave Cincinnati, Oh 45229 Timing: Fiscal Year 2003; Project Start 03-JAN-2003; Project End 30-NOV-2006 Summary: (provided by applicant): Normal lung development requires the temporally and spatially correct expression of numerous biologically-active molecules. Many of
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Chondroitin
these molecules are soluble and include hormones, growth factors, bioactive peptides, and cytokines. Components of the insoluble extracellular matrix (ECM), including proteoglycans (PGs), have also been shown to play important roles in normal lung growth and differentiation. PGs are a diverse class of molecules that serve as structural substrata in which tissues develop, act as binding reservoirs for specific growth factors, and mediate such processes as cell-ECM, cell-cell, and ligand-receptor interactions. Our preliminary experiments have shown that sulfated PGs are required for lung morphogenesis and epithelial differentiation. Further experiments demonstrated that disrupting one subclass of PGs, chondroitin sulfate proteoglycans (CSPGs), had marked inhibitory effects on lung growth and branching in vitro. From these data we have hypothesized that CSPGs play an essential role(s) in normal lung development. In this proposal, we will test this hypothesis in two phases. In the first phase (Specific Aims 1 and 2), we will use in vitro models to confirm and extend our preliminary observations that inhibition of PGs suppresses lung growth, morphogenesis, and epithelial differentiation, and to define which effects are due to the disruption of CSPGs. In the second phase (Specific Aim 3), we will determine how our in vitro observations translate to lung development in vivo. Conditional expression of chimeric bacterial chondroitinase(s) targeted to the lungs of transgenic mice will allow us to assess the importance of CSPGs in three distinct phases of lung development in vivo: branching morphogenesis, maturation of the pulmonary surfactant system, and postnatal alveolization. Completion of this project will fill a significant gap in our understanding of the role of CSPGs in lung morphogenesis and differentiation, and will determine whether disruption of CSPGs causes lung pathologies similar to clinical disease in neonates. This knowledge will allow the development of new strategies for the prevention and treatment of lung diseases resulting from lung hypoplasia and immaturity. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •
Project Title: COMPLEX CARBOHYDRATES OF NERVOUS TISSUE Principal Investigator & Institution: Margolis, Richard U.; Professor; Pharmacology; New York University School of Medicine 550 1St Ave New York, Ny 10016 Timing: Fiscal Year 2001; Project Start 01-DEC-1977; Project End 30-NOV-2003 Summary: We have isolated and biochemically characterized several chondroitin sulfate proteoglycans of brain identified with monoclonal antibodies, and will now extend this work using other available antibodies. We have also begun to determine the primary structure of a developmentally regulated chondroitin sulfate proteoglycan (designated 3F8), using amino acid sequence data for the synthesis of a cDNA probe by the PCR. The major objectives of our cloning studies include: a.) elucidating the structural relationship of 3F8 to other chondroitin sulfate proteoglycans of brain; b.) using cloned probes for in situ hybridization studies of its cellular sites of synthesis and tissue-distribution of message; c.) identification of core protein domains of potential functional importance, such as the growth factor-like and lectin-like sequences which we have found in another proteoglycan; and d.) eventual use of determined cDNA sequences of brain proteoglycans to better understand their biological functions by examining the effects of antisense constructs in transfected cells. We also plan to obtain information on the molecular interactions and specific biological roles of chondroitin sulfate proteoglycans in nervous tissue. In preliminary studies we have demonstrated that very low concentrations of the core proteins of characterized chondroitin sulfate proteoglycans of brain are capable of inhibiting the homophilic binding of the neuron-glia cell adhesion molecule, Ng-CAM. Using other model systems and cell adhesion molecules, we will
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now examine the possibility that extracellular chondroitin sulfate proteoglycans act as repulsive molecules which provide a mechanism for diminishing adhesive forces, thereby permitting cell rounding, division, differentiation, and cell movement in developing brain. Related studies will attempt to define the oligosaccharide binding specificity of the lectin-like domain present in the 1D1 (and possibly other) chondroitin sulfate proteoglycans of brain which we have isolated and characterized, and the roles of chondroitin sulfate proteoglycans in adhesive or repulsive processes will be studied by evaluating the effects of identified protein domains (expressed as fusion proteins) in cloned proteoglycans on cell-cell and cell-matrix interactions. Finally, we will determine the primary structure and cellular localization of a major heparan sulfate proteoglycan of brain which we have previously isolated and biochemically characterized. Amino acid sequence data derived from the 55 kDa core glycoprotein will be used for its cloning by our established PCR methodology. Cloning this putative membraneintercalated cell surface proteoglycan will also enable us to employ synthetic peptides or fusion proteins as immunogens for its immunocytochemical localization in developing brain at the light and electron microscopic levels, and will provide the foundation for transfection studies aimed at understanding its possible roles in such processes as cell adhesion and interactions with growth factors. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •
Project Title: COMPLEX FORMATION AND PROTEASE SPECIFICITY Principal Investigator & Institution: Bromme, Dieter; Associate Professor; Human Genetics; Mount Sinai School of Medicine of Nyu of New York University New York, Ny 10029 Timing: Fiscal Year 2002; Project Start 15-APR-2002; Project End 31-MAR-2007 Summary: (provided by applicant): The overall objective of the proposed research is to characterize the mechanism of interstitial collagen degradation by cathepsin K, the most potent mammalian collagenase presently known. Previously, cathepsin K was identified as the predominant cysteine protease in osteoclasts and the major type II collagen degrading activity in synovial fibroblasts. Unique among structurally related cathepsins and MMP collagenases, cathepsin K cleaves interstitial collagens at multiple intra-helical sites and similar to bacterial collagenases produces low molecular weight peptide fragments from type I and II collagens. It was demonstrated by the principal investigator that the collagenolytic activity of cathepsin K is dramatically enhanced in the presence of glycosaminoglycans (GAGs) and that the protease forms defined high molecular complexes with chondroitin sulfate, the major GAG in cartilage and bone. The proposed working hypotheses are that the collagenolytic activity of cathepsin K requires a specific complex formation with defined GAGs and that the complex exhibits a helicase as well as cleavage activity towards native triple-helical collagens. Furthermore, it is hypothesized that this complex form is unique for cathepsin K, and that the protease complex is the major intracellular collagen-degrading activity in mammalian cells. The physico-kinetic parameters of complex formation, the substrate specificity of the monomeric and complex forms of cathepsin K, the structural foundation of complex formation and specificity will be determined, and novel strategies to selectively inhibit the collagenolytic activity of the enzyme by inhibiting complex formation will be explored. Furthermore, the essential role of cathepsin K complexes in human collagen turnover will be determined. To achieve these goals, a wide range of biochemical, biophysical, cell-biological and structure-analytical methods will be employed. Altogether, these studies will characterize a novel mechanism for the
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Chondroitin
bulk collagen degradation in mammalian tissues and may offer a new strategy to block excessive collagen degradation in diseases such as osteoporosis and arthritis. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •
Project Title: ANTIGENICITY
COMPUTATIONAL
ANALYSIS
OF
CARBOHYDRATE
Principal Investigator & Institution: Woods, Robert J.; None; University of Georgia 617 Boyd, Gsrc Athens, Ga 306027411 Timing: Fiscal Year 2003; Project Start 01-MAR-1997; Project End 30-APR-2007 Summary: (provided by applicant): Group Beta Streptococcus and Neisseria meningitidis are leading causes of neonatal sepsis and meningitis. The increasing use of carbohydrate-based conjugate vaccines is founded on the observation that antibodies against the type-specific bacterial capsular polysaccharides (CPS) are often protective, and-is driven by the increasing prevalence of antibiotic resistant strains. However, the relationships between the carbohydrate sequence in the CPS and antigenicity are poorly understood. Similarly, the immune response to the CPS is structure-sensitive; some are poor immunogens and others good. The goal of this proposal is to provide an understanding of the structural features of antigenic oligosaccharides that are responsible for mediating the affinity and specificity of their interactions with antibodies. Ultimately, this information would form a basis for the rational development of more effective antibacterial vaccines. We have selected three systems (Aims 1-3) for study that display complementary levels of complexity. In Aims 1 and 2, we will use computational and experimental methods to determine the conformational properties of the bacterial CPSs from iV. meningitides and Group B Streptococcus, both free and bound to monoclonal antibody fragments. This information will provide a structural basis for interpreting the antigenicities and antibody specificities for these systems, as well as assist in the determination of the conformation of the immunodominant regions. To aid in the development and validation of the computational methods, in Aim 3, we will examine the properties of the related anionic sugars in glycosaminoglycans (GAGs), for which considerable experimental data exist. Computational methods, such as molecular dynamics (MD) simulations, are useful aids in the conformationat analysis of oligosaccharides and oligosaccharide-protein complexes; yet at present they have been developed only for neutral carbohydrates. The CPSs from N. meningitides and Group B Streptococcus, and from many other pathogenic bacteria, contain anionic carbohydrate residues. Accurate modeling of these molecules will require the extension and validation of our existing carbohydrate force field parameters (GLYCAM). To assist in this development, we will examine a number of anionic GAGs, such as hyaluronan, chondroitin and heparin sulfate as well as heparin, free and complexed to antithrombin III, whose conformational properties have been well characterized experimentally. Validation of the MD simulations will be based on comparisons with NMR and X-ray data and binding affinity measurements. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •
Project Title: COORDINATING ADHESION RECEPTORS IN AXON GROWTH Principal Investigator & Institution: Lilien, Jack E.; Professor; Biological Sciences; University of Iowa Iowa City, Ia 52242 Timing: Fiscal Year 2002; Project Start 01-AUG-2002; Project End 31-MAY-2007 Summary: (provided by applicant): Retinal ganglion cell axons are guided along their trajectories during development by many different systems of adhesion, attraction and
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repulsion. Proper axon growth and guidance requires integration in the growth cone of information from many distinct receptor systems. Our long term goals are to identify the environmental cues and signaling paths that integrate adhesion receptor function during development of axons in the neural retina. N-cadherin and beta1-integrins are two of the adhesion systems that play decisive roles in retinal axon elongation and guidance. We have discovered a pathway which coordinately regulates N-cadherin and beta1-integrin function during axon outgrowth. When cells or growth cones contact the chondroitin sulfate proteoglycan neurocan, both N-cadherin and beta1-integrin function is lost. This coordinate loss of function correlates with translocation of the non-receptor tyrosine kinase Fer from its usual association in the cadherin complex of proteins to the complex of proteins associated with the cytoplasmic domain of beta1-integrin. Our hypothesis is that coordinate regulation of cadherin and integrin plays an important role in preventing ganglion cell axons from straying from their appropriate path. The goal of this application is to define the role of Fer in cadherin and integrin function and to examine the role of this pathway in the development of retina ganglion cell axons. Aims 1 and 2 define the role of Fer in the function of cadherin and integrin respectively. We will identify effectors whose presence or phosphorylation is altered in the presence and absence of Fer and how these altered components regulate function. Aim 3 defines the regulatory site in the cadherin cytoplasmic domain responsible for transducing the signal initiating the shuttling of Fer. This will be accomplished by deletion and mutagenesis of N-cadherin, as well as functional comparison of other Type I and II cadherins present in the neural retina for the ability to participate in cross-regulation between cadherin and integrin. In Aim 4 we will determine the role of this cross regulatory circuit in development of retinal ganglion cell axon projections through inhibition of the binding of neurocan, the extracellular signal that initiates coordinate regulation, and through the use of cell permeable peptides to perturb cadherin and/or integrin function. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •
Project Title: CYTOADHERENCE IN MATERNAL MALARIA Principal Investigator & Institution: Gowda, Channe D.; Associate Professor; Biochem and Molecular Biology; Georgetown University Washington, Dc 20057 Timing: Fiscal Year 2001; Project Start 01-MAY-1999; Project End 31-DEC-2001 Summary: Recent studies suggest that during malaria infection in pregnant women, the placenta selects for a subpopulation of Plasmodium falcifarum by chondroitin 4-sulfate (C4S)-binding. In malaria endemic areas, primigravid women develop maternal malaria and susceptibility to the disease deceases as the gravid status increases, suggesting that women develop a level of protective immunity over successive pregnancies. Determination of the structural motif of the placental C4S that interacts with the parasite infected red blood cells (PRBCs), understanding of details of receptor-ligand interactions, studies on the immune response to C4S- specific parasite ligand in multigravid women living in malaria endemic areas, and studies on the nature and structure of the parasite ligand are likely to assist the development of therapy/vaccine for maternal malaria. This proposal focuses on C4S-mediated adherence of PRBCs to human placenta chondroitin sulfate proteoglycans (CSPG). Our preliminary results suggest that either a specific structural motif within the C4S chains of placental CSPGs binds PRBCs or the PRBC adherence to placenta CSPG may involve secondary interactions by either core proteins of CSPGs/co-purifying proteins after the initial C4Sspecific recognition. Preliminary studies also show that specific oligosaccharides inhibit PRBC adherence to placenta CSPG. The overall goals of this proposal are to: (1) Purify
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Chondroitin
human placental CSPGs, and study the glycosaminoglycan structures and PRBC binding characteristics of the CSPGs. (2) Determine whether the core proteins of CSPGs/co-purifying proteins participate in PRBC binding. (3) Immunofluorescence localization of PRBC- binding CSPG(s) in placenta. (4) Elucidation of the minimum size and fine structural specificity of the C4S motif that supports PRBCs adherence. (5) Evaluation of C4S ligand-specific immune protection in multigravid women living in malaria endemic areas. The long term goals of this study are to: (a) understand why placenta specifically selects for C4S-binding P. falciparum; (b) study the expression of the PRBC-binding receptor in placenta; (c) characterize the C4S- binding ligand on PRBCs; (d) study C4S oligosaccharides or oligosaccharide-mimetics for maternal malaria therapy; (e) develop C4S oligosaccharide-based drugs for maternal malaria therapy. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •
Project Title: DECORIN AND BIGLYCAN: STRUCTURE AND FUNCTION Principal Investigator & Institution: Mcquillan, David J.; Professor; Lifecell Corporation 1 Millenium Way Somerville, Nj 08876 Timing: Fiscal Year 2001; Project Start 31-MAR-1995; Project End 31-MAY-2005 Summary: (Adapted from applicant's abstract : The small leucine-rich repeat proteoglycans, decorin and biglycan, are biological modulators of extracellular matrix assembly and cell growth in health and diverse pathological conditions such as cancer and fibrotic disease Our central hypothesis is that these closely related members of the small leucine-rich proteoglycan family are multifunctional glycoconjugates that exert their regulatory effects by simultaneously acting on several targets, including: (1) binding to collagen and regulating the temporal and spatial kinetics of fibrillogenesis; (2) modulating the activity and availability of TGF-b, a cytokine that regulates cell proliferation, cell migration, and synthesis of matrix components; and (3) interacting with the epidermal growth factor receptor and thereby modulating cell proliferation. We have shown that the complex folding and post-translational processing of decorin and biglycan are critical to many of their functions. Furthermore, it is clear that the multitude of in vitro activities ascribed to decorin and biglycan may not be physiologically relevant in vivo, and the therapeutic potential of these molecules in fibrotic disease and cancer will only be realized by a systematic approach that demonstrates a direct link between biological activity and physiological response. The goal of this research is to advance understanding of decorin and biglycan biology by elucidating molecular mechanisms by which they regulate extracellular matrix assembly, matrix deposition, and cell growth. We will investigate and characterize in detail the interaction with type I collagen, modulation of TGF-b activity, and influence on EGF-receptor controlled suppression of cell growth. We will map specific binding sites through generation of recombinant proteoglycans, core proteins, decorin-biglycan chimeras, and leucine-rich repeat replacement mutants, wherein the native structure is maintained but specific protein binding domains are disrupted. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen
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Project Title: DECORIN DEFICIENCY IN HUTCHINSON-GILFORD PROGERIA Principal Investigator & Institution: Lemire, Joan M.; Anatomy and Cellular Biology; Tufts University Boston Boston, Ma 02111 Timing: Fiscal Year 2003; Project Start 01-JUN-2003; Project End 31-MAY-2005 Summary: (provided by applicant): Hutchinson-Gilford Progeria Syndrome (HGPS) is a rare "premature aging" syndrome of unknown etiology which is characterized by
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sclerodermatous skin changes, skeletal deformities, and severe global premature atherosclerosis. Extracellular matrix molecules play integral roles in all of the systems affected by HGPS. Published data and preliminary data from this laboratory have provided evidence for dramatically decreased production of decorin by HGPS and other progeroid fibroblasts. Decorin is an extracellular matrix proteoglycan involved structurally and in cell signaling in skin, blood vessels, skeletal and many other tissues. We will investigate the role of decorin as a potentially pivotal molecule for the HGPS disease phenotype. We will assess the consistency of this molecule as a disease marker by measuring all the available HGPS fibroblast lines, including parental fibroblasts, for decorin deficiency compared to age matched controls. We will begin to determine whether the decorin deficiency originates at the transcriptional or translational level using Northern and Western blot analysis, respectively. We will also determine whether HGPS fibroblasts have a more generalized defect in the ability to synthesize proteoglycans. For this analysis, total radio labeled proteoglycans from the media and cell layers of normal and HGPS fibroblasts will be 1) examined by SDS-PAGE gels and 2) quantitated by gel exclusion chromatography, before and after digestion with enzymes to remove their glycosaminoglycan chains. Finally, we will increase decorin expression experimentally in HGPS cells and determine whether various characteristic of the HGPS fibroblast phenotype are corrected. These studies should help: 1) identify targets for clinical manipulation, 2) find clues to the genetic defect by `backtracking' from our findings; and 3) further define a molecular phenotype for research studies and as a diagnostic tool. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •
Project Title: DETERMINATION OF OA PATHOLOGY BY BIOMARKER DATING Principal Investigator & Institution: Kraus, Virginia B.; Medicine; Duke University Durham, Nc 27706 Timing: Fiscal Year 2003; Project Start 30-SEP-2003; Project End 31-AUG-2008 Summary: Provided by Applicant): It is currently impossible to reliably distinguish an individual OA patient on the basis of a single biomarker at a single timepoint. Nevertheless, our work and that of others has identified several biomarkers associated with OA, including serum cartilage oligomeric matrix protein (COMP), serum hyaluronan, and various epitopes of type II collagen, to name a few. In this grant, we propose a novel strategy that is a refinement of current OA biomarker methods with the goal of improving upon the predictive capability of current OA biomarkers. This refinement is based upon measuring the fraction of D-aspartate in select cartilage macromolecules found in body fluids, in particular, type II collagen, and aggrecan. Amino acids exist in native proteins as the L-configurational optical isomer. The Lisomer is converted to the biologically uncommon D-isomer by a spontaneous process (racemization) that is dependent on time, temperature, and to a lesser extent pH. Although in general, racemization is a very slow process, aspartate is one of the 'fastest' racemizing amino acids; this enables its detection in proteins that are not renewed or have a slow turnover rate. Racemization of aspartate is also detectable in the two cartilage macromolecules in which it has been studied, collagen and aggrecan. The quantification of D-aspartate in these cartilage macromolecules has revealed the presence of distinct pools of molecules with different turnover rates ranging from 100400 years for collagen and from 3-25 years for aggrecan. We propose that the fraction of D-Asp in the fragments derived from these macromolecules present in the serum, urine and synovial fluid will reflect the degree of catabolism of the oldest pool of cartilage macromolecules. We will use established HPLC methods and develop ELISA based
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Chondroitin
methods to measure the fractional levels of D-Asp in select cartilage macromolecules in serum, urine and synovial fluid from OA and non-OA subjects. We hypothesize that quantification of the oldest type II collagen and aggrecan fragments in body fluids will better discriminate an OA subject from a non-OA subject than is possible with currently available OA biomarkers. We expect this refinement of current biomarker technology to yield valuable insights into the contribution of catabolic processes (high biomarker level with a high D-Asp content) versus anabolic processes (high biomarker level due to high turnover state but with a relatively low D-Asp content) to the level of a biomarker in an OA subject. We refer to the technique of quantifying the D-aspartate content of cartilage macromolecules as "biomarker dating". Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •
Project Title: DEVELOPMENT OF SENSORY INNERVATION PATTERNS Principal Investigator & Institution: Scott, Sheryl A.; Associate Professor; Neurobiology and Anatomy; University of Utah 200 S University St Salt Lake City, Ut 84112 Timing: Fiscal Year 2001; Project Start 01-MAR-1991; Project End 31-DEC-2002 Summary: During embryonic development, sensory neurons in dorsal root ganglia (DRGs) establish connections with central and peripheral targets quite precisely, which is essential for proper sensory function. DRG axons take characteristic routes to the periphery, where they innervate skin and muscle; central connections are established later. The overall goal of this project is to elucidate the mechanisms and molecules responsible for (1) directing the long-distance growth of sensory axons to targets in the limb and central nervous system and (2) regulating the distribution of cutaneous axons within skin. Innervation patterns mapped in embryonic chicks after experimental manipulations in ovo (Wang & Scott, 1998) suggest that sensory neurons have less robust pathfinding capabilities than motoneurons and are less rigidly specified. Aim I uses similar methods to investigate (a) whether there are differences in the pathfinding capabilities of thoracic and lumbosacral DRG neurons and (b) whether DRG neurons, like motoneurons, observe a waiting period period to invading the limb. In addition, Aim I uses in situ hybridization and in ovo perturbations to investigate whether ephrins and Eph receptors are involved in sensory axon pathfinding. In Aim II, central projections of DRGs that innervate aberrant skin regions following experimental manipulations will be mapped to learn whether central projections of cutaneous neurons, like those of muscle afferents, are determine by their peripheral targets. By assessing the pathfinding capabilities of sensory neurons, Aims I and II will provide valuable information about the extent to which sensory neurons are specific prior to axon outgrowth and the types of molecular cues that guide sensory axon growth. Once outgrowing sensory axons reach the skin, which is the largest sensory organ in the body, they ramify in a characteristic fashion. For example, in birds cutaneous innervation is restricted to the dermis, with few axons penetrating the epidermis. Aim III examines the role of two important classes of molecules, chondroitin sulfate proteoglycans and neurotrophins, in regulating the distribution of axons in skin in vivo and in several in vitro model systems. The increases understanding of the mechanisms and molecules responsible for the development of sensory innervation patterns that will be obtained here is of both developmental and clinical significance. This information will provide a framework for the design and implementation of clinical strategies to promote the extend and specificity of regeneration of injured or diseased sensory axons. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen
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Project Title: DEVELOPMENT OF THE PRIMARY OLFACTORY PATHWAY Principal Investigator & Institution: Treloar, Helen B.; Neurosurgery; Yale University 47 College Street, Suite 203 New Haven, Ct 065208047 Timing: Fiscal Year 2003; Project Start 01-MAY-2003; Project End 30-APR-2006 Summary: (provided by applicant): The long term aim of this project is to identify axon guidance molecules involved in establishing the complex topography of the primary olfactory pathway. We previously identified some critical time points in development where axon behavior indicates that guidance molecules are acting. Olfactory sensory neuron (OSN) axons grow from the olfactory placode to the telencephalic vesicle in early embryonic development. Axons penetrate the telencephalon, forming a presumptive olfactory nerve layer (pONL). A subset of axons grow to the ventricular surface, which by way of stimulating cell cycle kinetics, the formation of olfactory bulb (OB) is induced. The majority of axons remain restricted to the pONL for up to 4 days, presumably sorting out into like subsets. After 4 days, some axons grow deeper into the OB, initiating glomerular formation. What are the cue(s) that are present in the OB that prevent axon in growth prior to glomerular formation? What cues are present in the ONL that prevent dendritic outgrowth amongst axons? Do pioneer axons exist that initiate individual glomeruli? Do pioneer axons or groups of axons use cues in the developing OB to position themselves in the appropriate position prior to glomerular induction? One way to answer these key questions is to examine the distributions of candidate guidance molecules within the developing pathway. We hypothesize that the stalling of axons within the pONL may be due to inhibitory guidance molecules within the developing OB. One source of such inhibitory cues may be components of the extra cellular matrix (ECM). We have examined the expression patterns of four ECM molecules, tenascin, laminin, perlecan, and chondroitin sulfate proteoglycans (CSPGs). Of these, members of the tenascin family appear particularly good candidates for the inhibitory cues that regulate axon in growth and glomerular formation. The specific aims of the current application are to: 1) identify members of the tenascin family that are expressed in the developing OB during the period of glomerular formation; and 2) to functionally test the ability of theses molecules to inhibit OSN neurite outgrowth in vitro. These studies will greatly enhance our knowledge of how axons establish connections in the olfactory system and may have implications for diseases such as Kallman's syndrome. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen
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Project Title: EFFECT OF VERSICAN MUTATION ON LIMB DEVELOPMENT IN VITRO Principal Investigator & Institution: Capehart, Anthony A.; Biology; East Carolina University 1000 E 5Th St Greenville, Nc 27858 Timing: Fiscal Year 2002; Project Start 01-AUG-2002; Project End 31-JUL-2004 Summary: (provided by applicant): The long-term objective of the proposed research is to define the role of cell-extracellular matrix ECM) interactions in differentiation of cartilage, muscle, and nerve in their proper spatial relationships luring embryonic limb development. Recently, a recessive lethal insertional mutation in the Cspg2 gene was identified in a transgenic mouse line, hdf (heart defect). Cspg2 encodes the core protein of the chondroitin sulfate proteoglycan, versican, and hdf mutation results in loss of expression of the mature proteoglycan. Versican has been suggested to play a role in chondrogenesis and cellular patterning. However, little is known regarding details of versican function in the embryonic ECM. The hdf mutation offers a unique opportunity
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Chondroitin
to explore versican function in the limb. The specific aims of this proposal are to first analyze the spatial and temporal expression of versican during limb development in the hdf mouse. LacZ reporter histochemistry, in situ hybridization, and immunohistochemistry will be utilized to determine versican expression during limb development in carefully staged hemizygous hdf and wildtype mice to correlate localization with its hypothesized functions. Second, the role of the mature versican proteoglycan in precartilage aggregation during limb chondrogenesis in vitro will be evaluated. micromass cultures of hdf limb mesenchyme will be utilized to determine if this mutation results in inhibition of prechondrogenic mesenchymal condensation and subsequent cartilage differentiation. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •
Project Title: ENZYMATIC DE-INHIBITION OF AXONAL REGENERATION Principal Investigator & Institution: Muir, David F.; Pediatrics; University of Florida Gainesville, Fl 32611 Timing: Fiscal Year 2001; Project Start 02-APR-1999; Project End 31-MAR-2004 Summary: (Verbatim from the Applicant's Abstract): The inability of the spinal cord to regenerate has been attributed to the preponderance of molecules that inhibit axonal growth. Foundation studies support the contention that CSPG is a main inhibitory component in spinal cord tissue. However, findings also suggest that inhibitory CSPG may suppress the growth-promoting potential of normal adult peripheral nerve. Since nerve has an excellent capacity to regenerate, injury must evoke some mechanism by which the damaged nerve is converted from a suppressive environment to one that promotes axonal growth. If so, this conversion somehow fails to occur in damaged spinal cord. In vitro studies show that bacterial chondroitinase and human matrix metalloproteinase-2 (MMP-2) degrade and inactivate inhibitory CSPG present in neural tissues and that nerve and spinal cord tissues contain latent neurite-promoting activities that are revealed after treatment with these enzymes. Experiments in this proposal will test the following main hypotheses: a) enzymatic inactivation of CSPG enhances the neurite-promoting potentials of nerve and spinal cord; b) enzymatic inactivation of CSPG occurs during nerve degeneration; c) inactivation of CSPG during nerve degeneration is MMP-2-dependent and neuronal expression of MMP-2 provides a second, more discrete mechanism for negotiation of inhibited substrata and; d) contrasts in the regenerative capacity of nerve and spinal cord reflect differences in the inactivation of CSPG achieved during degeneration and by injured axons. Experiments that address these hypotheses are presented in five major Aims, all of which center on mechanisms to inactivate inhibitory CSPG and improve nervous system regeneration. Aims 1 and 2 focus on the inactivation of CSPG in the peripheral nerve by chondroitinase and MMP-2, respectively. Aims 3 and 4 focus on the actions of these enzymes in the spinal cord. The efficacy of enzyme applications and the neuritepromoting potential of treated nerve and spinal cord tissues will be assayed in vitro and their impact on axonal regeneration will be tested in several in vivo injury models. Aim 5 will determine die expression of CSPG- inactivating enzymes in the nervous system to better understand the roles of these enzymes in the regenerative process. This information will advance our understanding of the regulation of axonal growth by inhibitory mechanisms and will be applied to devise means to improve axonal regeneration by enzymatic inactivation of CSPG. The main goal of this project is to prove that application of CSPG-degrading enzymes within injured tissues is an effective therapy to improve axonal regrowth and recovery of function throughout the nervous system.
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Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •
Project Title: ESTROGEN: CHRODROPROTECTIVE OR DESTRUCTIVE? Principal Investigator & Institution: Frenkel, Sally R.; Associate Professor of Orthopedic; Hospital for Joint Diseases Ortho Inst Orthopaedic Institute New York, Ny 10003 Timing: Fiscal Year 2002; Project Start 30-SEP-2002; Project End 31-AUG-2004 Summary: This proposal responds to Research Topics 6.2., "Hormonal changes associated with increased risk for peri-and postmenopausal health problems," and 17, "Basic underlying mechanisms of musculoskeletal aging." The aim of the proposed study is to determine whether estrogen is chondroprotective or chondrodestructive, specifically with regard to the development or prevention of arthritis. In addition to estrogen, we will also examine the effects on cartilage of the specific estrogen receptor modulator (SERM) raloxifene, currently used in lieu of estrogen replacement therapy as a preventive and treatment for the postmenopausal patient population at risk for bone loss.This same population has an increased incidence of osteoarthritis (OA) with advancing age. It is therefore important to study the effects of this SERM alongside those of estrogen. The central hypothesis of this proposal is that estrogen has a positive effect on human chondrocyte metabolism and therefore helps to prevent degenerative arthritis. To establish this, we propose to examine the effects of estrogen and raloxifene in vitro on markers of cartilage metabolism and degradation. Real-time PCR will be used to quantitatively determine mRNA levels of these markers. Anabolic markers to be examined are type II collagen, cartilage oligomeric matrix protein, and aggrecan; catabolic markers will include interleukin-1 (IL-1) and matrix metalloproteinase-13. Chondrocytes will be grown in three-dimensional culture conditions in order to closely mimic the natural state. In addition, an exogenous catabolic mediator, IL-1, will be separately added to the estrogen and raloxifene cultures to determine whether estrogen or raloxifene can block IL-l-induced degradation of cartilage. The wide use of estrogen in the OA population makes it extremely important to elucidate whether estrogen and its related SERM raloxifene promote cartilage homeostasis or contribute to its degradation. The inconclusive and contradictory data from human and animal studies render the proposed studies highly significant. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen
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Project Title: GLIOGENESIS
FATE
OF
AGGRECAN-EXPRESSING
PROGENITORS
IN
Principal Investigator & Institution: Domowicz, Miriam; Pediatrics; University of Chicago 5801 S Ellis Ave Chicago, Il 60637 Timing: Fiscal Year 2003; Project Start 01-JUL-2003; Project End 30-JUN-2005 Summary: (provided by applicant): There is no definitive evidence regarding how precursor cells in the neuroepithelium switch from generating neuroblasts to generating glioblasts. Studies on the generation of glia cell types, in particular astrocytes, have been hindered by the lack of markers for their precursors and by their extensive migratory pathways. The principal investigator speculates that the cell-type switched to glioblast is distinguished by the differential expression of specific adhesion and extracellular matrix (ECM) molecules, reflecting the differential expression of transcription factors. The developmentally controlled expression of the aggrecan gene in brain ventricular zones during the active period of neuronal migration and gliogenesis suggests an important role for this molecule in neuronal-glial interactions. However, the specific functions and interactions in which aggrecan is involved in vivo remain unclear and will require
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further investigation. On the basis of the investigator's preliminary results, two hypotheses can be put forth with respect to the function of aggrecan during this process: 1) changes in the composition and/or structure of the ECM may influence the switching of precursor cells differentiating from neuroblast to glioblast cell-fates, or may influence the final glial phenotype (oligodendrocyte or astrocyte) that the precursors can become, and 2) alternatively, aggrecan may regulate the level of cell proliferation or affect the migration of the precursor cells which populate the brain. In order to distinguish between these possibilities a detailed study of aggrecan expression relative to that of different cell type markers, as well as of modifications in cell fate or proliferation associated with the lack of aggrecan expression in the aggrecan-deficient nanomelic mutant, will be the main focus of this proposal. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •
Project Title: FEASIBILITY OSTEOARTHRITIS
OF
INTERNET-BASED
TRIALS
FOR
Principal Investigator & Institution: Mcalindon, Timothy E.; Associate Professor; Medicine; Boston University Medical Campus 715 Albany St, 560 Boston, Ma 02118 Timing: Fiscal Year 2001; Project Start 30-SEP-1999; Project End 31-JAN-2003 Summary: The explosive growth in Internet use during the last few years has made it possible to communicate with greater numbers of people on-line than with any other technology. Recent software advances have made it possible to transmit and collect secure data from remote individuals over the Internet in an efficient and interactive manner. Thus, the internet has become an extraordinarily powerful potential resource for performing questionnaire-based research. One of the most enticing, yet unexplored, medical applications of the Internet is the possibility of performing clinical trials entirely on-line. Because of the vast scope of the Internet, it may be possible to study the attributes of various compounds which might otherwise never be evaluable in traditional clinic- based settings. For example, there exist a number of nutritional compounds which may be modestly effective in relieving osteoarthritis symptoms. Because of the large numbers and prohibitive costs involved in detecting efficacy from these compounds, it is unlikely that they will all be adequately evaluated in traditional clinical trials. The Internet, on the other hand, using validated symptom questionnaires, could have great utility in testing these safe compounds in the treatment of osteoarthritis. On the other hand, we need to learn about many factors which are critical to the feasibility of Internet-based trials, such as response rates, demographic characteristics of respondents, willingness of respondents to participate, validity of responses, protocol compliance, and participant retention. Our aim, therefore, is to evaluate aspects of the feasibility, utility and validity of performing a clinical trial using the Internet, by performing a model on-line trial of a glucosamine/chondroitin sulfate nutritional supplement among individuals with symptomatic knee osteoarthritis. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •
Project Title: FOLDING & MISFOLDING OF PARALLEL BETA-HELIX PROTEINS Principal Investigator & Institution: King, Jonathan A.; Assistant Professor; Biology; Massachusetts Institute of Technology Cambridge, Ma 02139 Timing: Fiscal Year 2002; Project Start 01-SEP-1978; Project End 31-AUG-2006 Summary: (provided by applicant): The pathways through which amino acid sequences direct the intracellular folding of polypeptide chains into beta-sheets and beta-helices remain unclear. This limits the ability to extract information from human and other
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genome sequences. An additional problem in biomedical research and the biotechnology industry is the failure of many protein chains expressed from cloned genes to fold into their native state, instead associating into inclusion bodies. Related protein misfolding and aggregation processes underly a number of human amyloid and protein deposition diseases.A subclass of beta-sheets is the processive parallel beta-helix fold. For the parallel beta-helix P22 tailspike trimer, partially folded intermediates in both in vitro and in vivo folding and inclusion body pathways have been characterized. In the past period of GM17,980, we have resolved additional subunit assembly intermediates, and isolated and characterized three new classes of folding mutants (in addition to temperature sensitive folding mutants, and their global suppressors); buried hydrophobic core mutants, triple beta-helix assembly mutants, and cysteine folding mutants. These identity sets of residues directing difterent stages of chain folding and assembly. Using monoclonal antibodies, we identified a role for the ribosome itself in tailspike nascent chain folding within cells. A triple stranded beta-helical region has been shown to act as a molecular clamp in subunit assembly. An algorithm has been developed for efficiently predicting beta-helices, which identifies surface proteins of many human pathogens as beta-helices. Human gamma-D crystallin mutants associated with juvenile onset cataract have been expressed and characterized, giving insight into their molecular pathology. In the next period, we propose to: a) Identify additional hydrophobic stack residues controlling parallel beta-helix folding in both the talispike and monomeric chondroitinase B; b) Identify early in vitro intermediates in the folding of beta-helices; c) Identity sequences which control the formation of the interdigitated triple beta-helix that acts as a molecular clamp; d) Test whether predicted beta-helices of Helicobacter pylori have the beta-helix structure; e) Pursue the unfolding, refolding and aggregation of the all beta-sheet human aamma-D crvstallin, which forms lens cataracts. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •
Project Title: FUNCTIONAL ORGANIZATION OF THE VISUAL SYSTEM Principal Investigator & Institution: Pearlman, Alan L.; Professor; Neurology; Washington University Lindell and Skinker Blvd St. Louis, Mo 63130 Timing: Fiscal Year 2001; Project Start 01-AUG-1978; Project End 30-NOV-2001 Summary: (from applicant's abstract): Major migratory events that take place during the development of the visual cortex define its structure, and thereby determine its function. The central goal of this project is to understand the molecular signals that lead to the systematic formation of layers in the visual cortex and guide the axons that innervate it. During cortical development, controlled numbers of neurons migrate along radial glia to form layers that have distinct connectional patterns and function, and growth cones of cortical efferent and afferent axons move through defined pathways to reach their targets. The cellular and molecular signals that control these vents are not well understood; defining them is an essential step in understanding the disruptive abnormalities that occur in human cortical development. In our prior studies we have identified specific extracellular matrix (ECM) components that are produced by migrating neurons and thalamocortical axons, and are expressed in axonal pathways. In the present proposal we will test hypotheses regarding the function of these ECM components and their receptors in neurons al and growth cone migration, and determine how a neurotrophin controls the size of an important population of ECMproducing neurons. In these studies we will carry out experimental perturbations in organotypic slice preparations that preserve the three dimensional structure of developing cortex for several days, as well as in dissociated cell culture and in vivo. We will use computer-aided cell recognition techniques to measure migratory distances of
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Chondroitin
labeled neuronal cohorts, and perturb ECM/receptor function with peptide fragments, antibodies, transfected dominant-negative gene constructs, and fusion proteins derived from a gene that is critical in cortical lamination. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •
Project Title: GENETIC ANALYSIS OF DERMATAN SULFATE IN VASCULAR BIOLOGY Principal Investigator & Institution: Gallo, Richard L.; Associate Professor; University of California San Diego 9500 Gilman Dr, Dept. 0934 La Jolla, Ca 92093 Timing: Fiscal Year 2003; Project Start 01-FEB-2003; Project End 31-JAN-2008 Summary: This project proposes to investigate the functions of dermatan sulfate in vascular biology and inflammation. Dermatan sulfate is the major glycosaminoglycan expressed in the extracellular matrix of the skin and has recently been found to be expressed on the luminal cell surface of vascular endothlium. Dermatan sulfate shares many functions with heparan sulfate but has been much less well studied. This is especially true regarding studies performed in vitro of the interactions of these sulfated glycosaminoglycans with growth factors, cytokines, enzymes, enzyme inhibitors and components of the coagulation cascade. We and others have found that in specialized circumstances dermatan is more effective than heparan sulfate in activating molecules such as heparan cofactor II, FGF-7 and HGF. The significance of superior activation by dermatan sulfate over heparan sulfate is not understood. In part, this is because molecular understanding of dermatan sulfate biosynthesis lags behind that of heparan sulfate. Thus, until now it has not been possible to selectively inhibit synthesis of either GAG. Critical to the synthesis and functions of dermatan is the epimerase responsible for conversion of D-glucuronic acid (GIcA) to L-iduronic acid (IdeA), the 2-Osulfotransferase that modifies the Liduronic acid (DS 2OST), and the 4-Osulfotransferase (DS 4OST) that completes the assembly of the characteristic disaccharide unit of dermatan sulfate. DS 4OST and DS 2OST are now known and provide immediate targets to apply tools of murine genetic for evaluation of the in vivo functions of dermatan sulfate. Identification of the epimerase is also important to complete understanding of the biosynthesis of dermatan and further genetic analysis. Therefore, the goals of this project are to take advantage of the strengths of the PPG to understand the function of dermatan sulfate in vascular biology. Specifically, our plans are to target for deletion DS 2OST and DS 4OST using the Cre-loxP recombination system and identify and clone the critical dermatan sulfate epimerase. Mice lacking normal synthesis of dermatan sulfate will by systematically evaluated for defects in tissue histology, hematology and coagulation, wound repair and the ability to resist infection. These studies should provide new insight into the functions of dermatan sulfate under normal homeostatic conditions and in resistance to disease. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen
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Project Title: GLIAL RESTRICTED PRECURSORS AND SPINAL CORD REPAIR Principal Investigator & Institution: Davies, Stephen J.; Neurosurgery; Baylor College of Medicine 1 Baylor Plaza Houston, Tx 77030 Timing: Fiscal Year 2003; Project Start 01-AUG-2003; Project End 31-JUL-2007 Summary: (provided by applicant): The primary focus of this research application is the development of an in vivo model of traumatic adult mammalian spinal cord injury with which to study the glial and matrix biology of spinal cord scar formation and characterize the ability of glial-restricted precursors (GRPs) and GRP-derived astrocytes
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(GDAs) to differentiate within forming glial scar tissue, suppress scar formation and provide an axon growth support bridge for axon regeneration. Preliminary data from our laboratory shows that spinal cord scar tissue is rich in a variety of axon growth inhibitory chondroitin sulfate proteoglycans (CSPGs), several of which are associated with astrocytes and adult glial progenitors that accumulate at sites of injury. Interestingly, although adult glial precursors can generate both astrocytes and oligodendrocytes in vitro, astrocytes are the predominant macroglia observed within spinal scar tissue. Experiments in aim 1 will therefore test the hypothesis that the environment of adult spinal scar tissue favors astrocytic differentiation, by transplanting a defined population of tripotent glial-restricted precursors (GRPs) directly into an acute stab injury of adult rat dorsal column white matter and quantifying the proportions of astrocytes and oligodendrocytes that these cells generate. As controls for the possible effects of scar tissue and axotomy on GRP differentiation, the macroglial differentiation of GRPs in the absence of glial scar tissue within intact white matter alone and in the presence of growing axons from adult neurons, will be investigated using an atraumatic micro-transplantation technique. Embryonic GRPs can be induced to differentiate into type-1 astrocytes or type-2 astrocytes in vitro. The generation of these two distinct astrocytic populations from GRPs in vitro permits an investigation of the impact of each of these distinct astrocytic cell types on scar formation and axon regeneration in vivo. Unlike adult astrocytes or type-2 astrocytes, type-1 astrocytes express low levels of CSPGs and transforming growth factor betas (TGFbetas) known to induce CSPG deposition in CNS scar tissue. In aim 2, quantitative western blot and confocal microscopy analysis will test the hypothesis that intra-lesion transplants of type-1 GDAs will suppress TGFbeta and CSPG levels within spinal cord scar tissue compared to type2 GDAs or control lesions. Preliminary results show that type-1 GDAs are highly supportive of axon growth in vitro. Experiments in aim 3 will therefore test the hypothesis that intra-lesion transplanted type-1 GDAs will retain their axon growth supportive phenotype and promote axon regeneration across spinal cord injuries. Micro-transplantation and axon tracing techniques will be used to compare the ability of type-1 GDAs and type-2 GDAs grafted into injured spinal cord to support regeneration of adult sensory and corticospinal axons at acute to chronic time points post injury. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •
Project Title: GLUCOSAMINE DEGRADATION
IN
CARTILAGE
HOMEOSTASIS
AND
Principal Investigator & Institution: Shikhman, Alexander R.; Scripps Research Institute 10550 N Torrey Pines Rd La Jolla, Ca 920371000 Timing: Fiscal Year 2001; Project Start 01-JUN-2000; Project End 31-MAY-2005 Summary: Glucosamine represents one of the most commonly used over-the- counter drugs to treat osteoarthritis. However, the molecular mechanisms involved in the realization of its anti-arthritic activities are still poorly understood. Recently, we discovered that glucosamine (GlcN) and its derivative, N-acetylglucosamine (GlcNAc), express a broad range of anti-inflammatory activities in cultured human articular chondrocytes stimulated with interleukin-1beta (IL-1beta). These activities include inhibition of IL-beta induced nitric oxide (NO) production, IL-6 and COX-2 synthesis. In contrast, GlcNAc does not affect constitutively expressed COX-1 protein. These data have allowed us to generate a working hypothesis proposing that GlcN and its derivatives may beneficially affect the impaired cartilage metabolism in OA, which eventually could result in restoration of extracellular cartilage matrix and chondrocyte homeostasis. Therefore, the goal of the proposed project is to analyze the influence of
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Chondroitin
GlcN and GlcNAc on homeostasis of normal and osteoarthritic human articular chondrocytes and to study the effect of these agents on quantitative and qualitative changes in extracellular matrix glycosaminoglycans. The aims of the study are: 1) to study the effect of GlcN and GlcNAc on production of glycosaminoglycans, including hyaluronic acid, chondroitin-6 sulfate, chondroitin-4 sulfate, dermatan sulfate, and keratan sulfate, in cultured human chondrocytes isolated from normal and osteoarthritic joints; 2) to investigate in vitro chondroprotective effect of GlcNAc on glycosaminoglycan degradation induced by IL-1beta; 3) to study the effect of GlcNAc on the activity of selected lysosomal glycosidases in cultured human articular chondrocytes stimulated with IL-1beta; 4) to correlate the biological activities of GlcN and GlcNAc with the age of chondrocyte donors; 5) to analyze the effect of G1cN and GlcNAc on chondrocyte apoptosis; 6) to examine the effect of G1cN and GlcNAc on TGFbeta and IGF-1 production in cultured human articular chondrocytes. Results of the study will broaden our understanding of the mechanisms of chondroprotection, and will serve as a starting platform for the identification of new molecular targets involved in the pathogenesis of osteoarthritis. The potential practical value of this project is that the obtained experimental data could be used as a basis for the design of a new class of the pharmacological agents capable of preventing or may be even restoring cartilage loss in the joints affected by arthritis. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •
Project Title: HEPARIN COFACTOR II ACTIVATION MECHANISM Principal Investigator & Institution: Foshay, Miriam C.; Biochem and Molecular Biology; University of Illinois at Chicago 1737 West Polk Street Chicago, Il 60612 Timing: Fiscal Year 2003; Project Start 01-JUN-2003; Project End 31-MAY-2006 Summary: (provided by applicant): Heparin cofactor II (HCII) is a thrombin inhibitor found in relatively high concentration in plasma and in most tissues of the body. A member of the serpin superfamily, it is important to the prevention of thrombosis and arteriosclerosis. Heparin and dermatan sulfate accelerate its rate of inhibition 10[3] to 10[4]-fold through an allosteric mechanism that is only partly understood. This unique mechanism appears to involve binding of the N-terminus of HCII to exosite I of thrombin following the binding of glycosaminoglycans (GAG). Although some of the residues involved in this mechanism have been identified through site-directed mutagenesis, the structural changes that occur have not been identified. Another unusual feature of HCII is its active site sequence, which makes the serpin more sensitive to activation by particular GAG and therefore confers greater site specificity. This proposal seeks to use a combination of heteronuclear single quantum correlation (HSQC) NMR and fluorescence spectroscopy to elucidate in solution the sequence of events leading to HCII activation. A proposed model will be tested through the following specific aims 1) to determine the relative mobility of the N-terminus and its binding site(s), including the binding site of the hirudin-like acidic region, 2) to establish the activation mechanism by monitoring changes following the binding of heparin and dermatan sulfate, and 3) to determine whether the reactive center loop is partially inserted in beta-sheet A, and whether that insertion is affected by the binding of GAG. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen
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Project Title: HUMAN CHONDROCYTE CELLS IN CONTINUOUS CULTURE Principal Investigator & Institution: Hay, Robert J.; Robert H, Llc 10801 University Blvd Manassas, Va 20110
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Timing: Fiscal Year 2003; Project Start 10-JUN-2003; Project End 30-NOV-2003 Summary: (provided by applicant): The primary objective of this proposed program is to extend the life-span of normal human chondrocyte cell cultures to develop continuous lines for distribution to the research community and for tissue engineering. Some existing 50 chondrocytic strains are available for study. The consequence(s) of constitutive expression of human telomerase reverse transcriptase (hTERT) will be determined. The human cDNA clone for hTERT has been cloned in the retroviral expression system pLXSN for ready transfection to selected human cell strains. Introduction of this gene has been shown to immortalize cells of some systems. Reports with chondrocyte cell lines are needed. Functionality and doubling potential of chondrocytic lines will be assessed both before and after transfection. Histoenzymological, immunohistochemical, and molecular tests are proposed. The expression of hTERT will be determined using the TRAP (Telomeric Repeat Amplification Protocol) assay. To assess the functional consequences of the constitutive or periodic expression of hTERT, a series of structural and phenotypic tests will be performed. Positive controls will consist of related lines normal or immortalized in similar fashion but with the HPV16 E6/E7 genes (on hand). Thus, our cell line generation and engineering strategy should provide sets of potentially therapeutic populations for further developmental and transplantation research. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •
Project Title: IMPROVED SURGICAL ANTICOAGULATION USING A HCII AGONIST Principal Investigator & Institution: Cardin, Alan D.; Celsus Laboratories, Inc. 12150 Best Place Cincinnati, Oh 45241 Timing: Fiscal Year 2001; Project Start 01-MAR-2001; Project End 31-AUG-2002 Summary: (Investigator's abstract) Thrombin bound to fibrin, the vessel wall and/or to extracorporeal surfaces is resistant to inhibition by heparin/antithrombin Ill (HAT). Intimatan, a dermatan disulfate semi-synthetically enriched in iduronic acid-N-acetyt-Ogafactosamine 4,6-O-disulfate, mediates the sustained inhibition of surface-bound thrbmbin. Intimatan, a potent heparin cofactor II (HCII) agonist, targets HCII to the same exosite of thrombini targeted by hirudin but not by RAT. In the pig model of cardiopulmonary bypass surgery (CPB), Intimatan, relative to heparin, maintained extra-corporeal patency at a 10-fold lower anti-thrombin dose, generated a 4-fold lower activated clotting time (ACT) and reduced bleeding 2-fold without anticoagulant neutralization. Presently unknown is whether Intimatan interacts with heparin-induced thrombocytopenia (HIT) antibody or its hemorrhagic effect relative to danaparoid and hirudin. These anticoagulants, although approved for HIT, are neither optimally safe or effective in CPB and this patient population most often develops heparin antibody. The specific aims of the Phase I STTR are to determine (relative to the anticoagulants currently approved for HIT): (1) the HIT cross-reactivity of Intimatan and its potential to ameliorate heparin/heparin antibody platelet activation; (2) its antithrombotic potency and (3) its hemorrhagic effects. It is anticipated that these studies will further the development of Intimatan for CPB based on a superior therapeutic profile and mechanism of action. PROPOSED COMMERCIAL APPLICATION: The composition of matter and use claims of intimatan as an inhibitor of thrombin generation and complement activation issued in 1999 in U.S. Patent 5,922,690. The differentiated mechanism of action of Intimatan provides a competitive advantage over existing modalities for the prevention/treatment of a wide vista of thrombo-embolic disorders in terms of lower manufacturing cost, enhanced anticoagulation efficacy against pathologic
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thrombosis and in device/procedure settings (CPB, dialysis, angioplasty, stents, cardiac assist devices), lower dosages, less bleeding, use in HIT patients and amelioration of hypercoagulability in HIT. Its value as a radiopharmaceutical for medical imaging of vascular diseases (including treatment of cancer) having a thrombin component is also realized. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •
Project Title: IN VITRO GENERATION OF CARTILAGE FROM FIBROBLASTIC CELLS Principal Investigator & Institution: French, Margaret M.; Bioengineering; Rice University 6100 S Main Houston, Tx 77005 Timing: Fiscal Year 2003; Project Start 15-MAY-2003; Project End 30-APR-2006 Summary: (provided by applicant): Cartilage injuries and osteoarthritis affect over fifty million people each year and as of yet, there is no "cure" for their condition. The long term objective of this proposal is to develop an in vitro system for generating articular cartilage using fibroblastic cells, which can then be used in future repairs of cartilage. The specific aims will address the need for engineered cartilage and also the source of cells for the construct. Initially, (SA1) fibroblastic cells will be tested for the ability to differentiate into chondrocytes in monolayer culture when placed under various culture conditions. Differentiation will be assessed by expression of chondrocyte genes. Secondly, (SA2) these cells will be cultured in a three dimensional construct to determine to what extent they can form functional cartilage. This aim will have direct bearing on the application of adult "non-stem cells" in tissue engineering. Finally, (SA3) the cells will be transfected with anti-inflammatory or inhibitors of matrix degredation prior to three dimensional culture to examine the possibility of including these selfdefense mechanisms in cartilage to be transplanted into patients. This would allow for the development of engineered tissues that are more able to withstand the transfer into a damaged environment. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen
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Project Title: IN VIVO ROLE OF PROTEOGLYCANS IN GROWTH FACTOR SIGNALING Principal Investigator & Institution: Marsh, J L.; Associate Professor; Developmental and Cell Biology; University of California Irvine Campus Dr Irvine, Ca 92697 Timing: Fiscal Year 2001; Project Start 01-JAN-1998; Project End 30-JUN-2003 Summary: A central problem in biology is how to spatially regulate paracrine signals in tissues. Experiments in vitro suggest that heparan sulfate and chondroitin sulfate containing glycosaminoglycans (GAGs) and/or the proteins to which they are attached are important for modulating growth factor signaling. However, in vivo evidence to support this view has been scanty, in part because mutations that disrupt the production of GAG polymers and the core proteins have not been available. We have identified the suppenkasper gene (ska) in Drosophila and found that it encodes UDP-glucose dehydrogenase which is essential for the production of gluconate containing disaccharides which, in turn, are the building blocks of heparan and chondroitin sulfate GAGs. Surprisingly, mutations in this general metabolic gene produce mutant phenotypes suggesting a specific block in wingless signaling. Following this, we have also found that mutations in the Drosophila syndecan gene, a major source of heparan sulfates in vertebrates, interact genetically with mutations of dishevelled, a key component of the wingless signaling pathway. These observations demonstrate that
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proteoglycans and GAGs are important for growth factor signaling in vivo. However, they raise questions about the mechanism of action of syndecan in growth factor signaling in general and wingless signaling in particular. We propose to explore those mechanisms and to test a coreceptor model, a co-clustering model and a diffusion regulator model of the postulated Syndecan/Wingless interaction. These questions can be addressed by testing the effects of modified transgenes in vivo using developmental and genetic approaches. The involvement of proteoglycans in Wnt and possibly other growth factor signaling pathways adds a new dimension to the mechanism of signal transmission between cells. Both syndecan and suppenkasper have highly conserved homologs in mammals implying possible conservation of function. In addition, the wingless gene of Drosophila encodes a homologue of the tumor producing Int-1 oncogene of mammals and the dishevelled, shaggy and armadillo genes are all highly conserved downstream components of wingless signaling and are functionally interchangeable between vertebrates and Drosophila. Thus these studies will foster our understanding of the principles governing growth factor signaling in general and the WG signaling pathway in particular. Further, these in vivo studies may help in understanding the basis of some dysmorphologies in humans. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •
Project Title: INTERMOLECULAR PHYSICAL INTERACTIONS IN CARTILAGE Principal Investigator & Institution: Eppell, Steven J.; Assistant Professor; Biomedical Engineering; Case Western Reserve University 10900 Euclid Ave Cleveland, Oh 44106 Timing: Fiscal Year 2001; Project Start 30-SEP-1998; Project End 31-AUG-2003 Summary: The long-term objective of this research effort is to find preventative and/or curative measures for osteoarthritis by enhancing understanding of the molecular and sub-molecular scale pathogenesis of this disease. The central hypothesis of this proposal is that the location and magnitude of submolecularly localized charge domains on type IX collagen are important in the interaction between collagen fibrils and aggrecan molecules in the cartilagenous extracellular matrix (ECM). Type II collagen fibrils are hypothesized to link to the aggregated proteoglycan matrix via an electrostatic interaction between negatively charged sulfate groups on aggrecan glycosaminoglycan side chains and the theoretical highly positively charged non-collagenous 4 (NC4) domain of type IX collagen which is covalently bound to the surface of the type II fibrils. There is substantial circumstantial evidence that this interaction is crucial in obtaining and maintaining normal viscoelastic biomechanical function of the ECM. The work proposed will provide a direct measurement of this interaction. In addition, in vitro submolecular scale measurements of the conformation and charge distribution of purified monomers of type II and type IX collagen and aggrecan will be obtained. This information will be critical in the development of the next generation of molecularlybased theoretical models of ECM biomechanics. The Specific Aims of the proposal are to: 1) image individual surface resident type II and type IX collagen and aggrecan molecules under ambient and in vitro conditions; 2) measure the force fields generated by each of the molecules; 3) measure the force of interaction between chondroitin sulfate (CS) and type II and type IX collagen; and 4) measure the force of interaction between aggrecan and type II and type IX collagen molecules. These aims will be accomplished using an atomic force microscope to probe molecules immobilized on a surface. By analyzing data in the snap-to-contact portion of a standard force-distance curve, the magnitude of charges on the collagen and aggrecan molecules will be obtained (Aim 2). The small size of the end of the AFM probe tip allows for this measurement to be made with sub- molecular spatial resolution. Aims 3 and 4 involve
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covalent attachment of CS and aggrecan to an AFM probe tip. Subsequent analysis of the adhesive region of the force-distance curve will yield the forces of interaction. The applicant suggests that results of the proposal experiments will unequivocally answer the question of whether type IX collagen is capable of participating in an electrostatic interaction with aggrecan that is strong enough to hold cartilage together under physiological conditions. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •
Project Title: MALARIA AND HIV IN PREGNANT WOMEN IN MALAWI Principal Investigator & Institution: Meshnick, Steven R.; Professor; Epidemiology; University of Michigan at Ann Arbor 3003 South State, Room 1040 Ann Arbor, Mi 481091274 Timing: Fiscal Year 2001; Project Start 15-MAR-2001; Project End 30-SEP-2001 Summary: Approximately 500,000 HIV-infected children are born each year in subSaharan Africa. Nevirapine treatment programs could prevent about half of these infections. In Arica, maternal malaria is common and frequently causes low birth weight. Important interactions between HIV and malaria infections in pregnant women have been identified ane low-cost interventions to prevent maternal materia are known. The current proposal aims to test the following hypotheses: 1. Maternal malaria increases mother-to-child transmission (MTCT) of HIV in nevirapine-treated women and children; malaria may have this effect by increasing maternal viral load, placental monocytes, and placental concentrations of TNF-alpha and CCR5; and 2. HIV-1 infections inhibit the development of pregnancy-specific anti-malarial immunity and exacerbates maternal malaria. To test these hypotheses, we will enroll approximately 1400 women at antenatal clinics in Blantyre, Malawi. HIV-positive women and their offspring will be treated with nevirapine. 400 HIV-positive women will be enrolled in a prospective cohort study in which the effects of maternal malaria. To test these hypotheses, we will enroll approximately 1400 women at antenatal clinics in Blantyre, Malawi. HIV-positive women and their offspring will be treated with nevirapine. 400 HIV-positive women will be enrolled in a prospective cohort study in which the effects of maternal malaria on HIV transmission rates will be determined. In this same group of women, we will investigate how malaria affects maternal peripheral and placental viral loads, placental histopathology, and placental and cord blood cytokine and chemokine levels. In a second substudy, the effects of HIV on pregnancy-specific antimalarial immunity (antibodies to chondroitin sulfate. A binding infected erythrocytes) will be assessed in 4 groups of 52 multigrivida (HIV+/malaria+, HIV+/malaria-). The results of this study will have important implications for designing public health program s for antenatal care in African and should promote our understanding of the pathogenesis of MTCT. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen
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Project Title: MATERNAL MALARIA--PARASITE ADHESION AND ANTIBODIES Principal Investigator & Institution: Duffy, Patrick E.; Director; Seattle Biomedical Research Institute 4 Nickerson St, Ste 200 Seattle, Wa 98109 Timing: Fiscal Year 2001; Project Start 01-JUL-1998; Project End 30-JUN-2004 Summary: This application proposes to describe the variant and invariant properties of CSA-binding proteins expressed by the malaria parasite, and to understand the mechanisms by which women develop humoral immunity which prevents parasite adhesion to CSA. Specifically, we will identify var gene products, unique transcripts,
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and CSA-binding proteins expressed by the malaria parasite: each of these approaches provides the opportunity to identify molecules involved in parasite-CSA interactions. RT-PCR will be employed to amplify var gene products from placental field isolates defined as CSA-binding; these amplified transcripts will be compared with var genes expressed by field isolated obtained from non-pregnant donors. Subtraction will employ subtractive PCR and subtraction libraries to identify gene transcripts unique to CSAbinding parasites from the placenta (and therefore not common with CD36-binding parasites from non-pregnant donors); these and other expression libraries can be screened with labeled CSA or with sera from multigravid women. CSA-binding proteins will be purified on CSA affinity columns, then employed in assays to characterize function as well as obtain peptide sequence; this information will be used to design oligonucleotide probes to screen libraries for full length sequence. We will then determine conserved and variant properties of these molecules, explore their contribution to parasite adhesion in the placenta, and identify epitopes targeted by naturally occurring antibodies known to inhibit parasite adhesion to CSA. Sequence variation and conserved motifs will be explored by aligning the molecules identified by the above methods. This information will be placed in the context of binding function by examining recombinant protein fragments for evidence of adhesion. We hypothesize that CSA- binding molecules expressed by the malaria parasite can take variant or distinct forms, but that motifs involved in binding are conserved, or that epitopes targeted by anti-adhesion antibodies are conserved or limited in their degree of variation. Therefore, in conjunction with the sequence and functional characterization of these molecules, we will determine the epitopic specificity of antibodies which block parasite binding to CSA. This information will provide the first full characterization of tissue-parasite adhesion in an accessible tissue, and may provide a model to examine other malaria syndromes. Further, the delineation of binding domains and B cell epitopes will provide the basis to design an anti-adhesion vaccine to protect primigravid and other women susceptible to placental infection with the CSA-binding parasites. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •
Project Title: MATRIX METALLOPROTEINASES AND REGENERATION AFTER TBI Principal Investigator & Institution: Phillips, Linda L.; Associate Professor; Anatomy and Neurobiology; Virginia Commonwealth University Richmond, Va 232980568 Timing: Fiscal Year 2002; Project Start 15-MAY-2002; Project End 30-APR-2007 Summary: (provided by applicant): The extent of long-term functional recovery following traumatic brain injury (TBI) is clearly associated with the capacity for adaptive synaptic plasticity within injured circuitry. Recent evidence supports a role for extracellular matrix proteins (ECMs) and their regulatory metalloproteinases (MMPs) in neurite growth and synaptic reorganization after CNS trauma. Given that these molecules are found within brain regions vulnerable to TBI, we have begun to examine members of the gelatinase and stromelysin MMP families during injury-induced synaptic plasticity. We hypothesize that the interaction of MMPs and their ECM substrates during synaptic reorganization determines the success of long-term recovery following TBI. Specifically, we posit that MMPs control ECM dissociation during removal of degenerating terminals, and subsequently regulate distribution of ECM associated molecules involved with synaptogenesis. Our approach will first identify the spatio-temporal pattern of MMP expression and functional activity after unilateral entorhinal lesion (UEC), an insult which induces the well-defined process of reactive synaptogenesis within the hippocampus. The neuronal plasticity induced in this model
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results in adaptive restoration of synaptic structure and function. With the UEC pattern as a baseline for comparison, we will profile MMP expression and function after brain trauma using the rat TBI model which combines excessive neuroexcitation of percussive injury with targeted hippocampal deafferentation of entorhinal lesion (TBI+BEC insult). We have shown that this model reliably produces a persistent, maladaptive synaptic plasticity and severe long-term cognitive deficits. Initially, we will examine both protein (LM/EM immunohistochemistry, Western blots) and mRNA (RT-PCR, Northern blot and/or in situ hybridization) expression for select MMPs (gelatinases A and B; stromelysin) and their associated ECM substrates (collagenase IV, chondroitin sulfated proteoglycan, enascin) after injury. Additional experiments will determine how effects on protein and mRNA are correlated with MMP enzyme activity (gel zymography and chromogenic enzyme assay). Next, we will establish whether these injury-induced changes in MMPs/ECMs are associated with alterations in electrophysiological measures of synaptic plasticity (LTP, paired-pulse facilitation, current-source-density analysis) and changes in cognitive outcome (Morris Water Maze performance). Finally we will test the association between MMPs and synaptic reorganization following TBI by: 1) applying specific MMP inhibitors and assessing the extent of synaptic plasticity generated, and 2) enhancing injury-induced plasticity with compounds targeting NMDA and dopamine receptors and then assessing MMP expression and functional activity. Together, these studies will establish whether or not MMPs play a role in regenerative processes evoked by TBI and potentially identify novel therapies for brain trauma victims. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •
Project Title: MECHANICAL SIGNAL TRANSDUCTION MECHANISM OF CHONDROCYTES Principal Investigator & Institution: Valhmu, Wilmot B.; Assistant Professor; Surgery; University of Wisconsin Madison 750 University Ave Madison, Wi 53706 Timing: Fiscal Year 2003; Project Start 30-SEP-1996; Project End 30-JUN-2007 Summary: The primary objective of this proposal (for competing continuation of R29/R01 AR43597) is to further elucidate the mechanisms through which the phospholipase C/inositol trisphosphate/calmodulin and adenylyl cyclase/cyclic AMP (cAMP) signaling pathways mediate transduction of compression-induced signals in chondrocytes, resulting in regulation of gene expression. Mechanical forces are key regulators of cell activity, morphology and function. The resident chondrocytes sense and respond to these stresses and strains by altering their metabolic and biosynthetic activities. Although the responses of articular cartilage or chondrocytes to mechanical modulation have been extensively studied, the mechanisms whereby the cells sense and transduce signals generated by the applied mechanical forces are much less understood. Work performed so far in R29/R01 AR43597 has shown that the compression-induced transient elevation of aggrecan gene expression in articular cartilage requires signaling through the adenylyl cyclase/cAMP and phospholipase C/phoshphoinositol (PI) signaling pathways. Further characterization of the signaling process revealed that 1) protein kinase C activity is not required, 2) transduction of the compression-induced signals is inositol 1,4,5-trisphosphate (IP3)-dependent, 3) changes in intracellular Ca 2+concentration are required, and 4) the activities of Ca2+/calmodulin (CAM), CaMdependent protein kinase II and partially calcineurin are required. This competitive renewal application proposes to test the hypothesis that the CREB/CBP complex functions as a common transcriptional mediator of the compression-induced signals transduced through the cAMP and CaM-dependent signaling pathways, leading to
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regulation of aggrecan gene expression. The roles of downstream effector molecules of the cAMP and CaM-dependent pathways in compression-induced modulation of CREBmediated regulation of aggrecan gene expression will be investigated. Data obtained from these studies will enhance our understanding of mechanisms, operating downstream of cytoplasmic second messengers, whereby compression and other physical forces modulate chondrocyte biosynthetic activities and function. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •
Project Title: MECHANISMS OF A NOVEL CHEMOTACTIC COFACTOR FOR C5A Principal Investigator & Institution: Kew, Richard R.; Pathology; State University New York Stony Brook Stony Brook, Ny 11794 Timing: Fiscal Year 2001; Project Start 01-JUL-2001; Project End 30-JUN-2006 Summary: (provided by applicant): Chemotaxis of leukocytes into various tissues is known to be a critical step in the pathogenesis of several inflammatory disorders. Complement pro-inflammatory peptides C5a and C5a des Arg also have been implicated in disease pathogenesis. C5-derived peptides are very potent chemoattractants for a wide variety of cell types. Much is known about the bioactivities of C5-derived peptides but the regulation of these functions is poorly understood. Previously, we were the first of several groups to demonstrate that the vitamin D binding protein (DBP), also known as Gc-globulin, can enhance the chemotactic activity of C5a and C5a des Arg, i.e., function as a co-chemotaxin. Moreover, the co-chemotactic activity of DBP is specific for the C5-derived peptides. Although DBP appears to be a physiologically important regulator of the chemotactic activity for activated complement, the mechanism of chemotaxis enhancement by DBP is not known. Recently, we have reported several important observations that should help define the mechanism by which DBP acts as a co-chemotactic factor for C5a. (1) DBP needs to be bound to the cell surface in order to function as a co-chemotaxin for C5a. (2) The neutrophil DBP binding site is a chondroitin sulfate proteoglycan. (3) Expression of the DBP binding site is regulated by cell surface-bound neutrophil elastase, which cleaves and sheds the proteoglycan. (4) Preliminary studies have shown that activated platelets modify DBP to an active co-chemotactic form. (5) Clinical samples from patients with inflammatory disorder (ARDS) contain the modified co-chemotactic form of DBP. It is our hypothesis that a modified form of DBP binds to the cell surface and initiates an enhanced chemotactic response to C5a. In this proposal, we endeavor to investigate the mechanism by which DBP augments the leukocyte chemotactic activity of C5a by utilizing human neutrophils and the U937 cell line transfected with the C5a receptor (U937-C5aR). The process of co-chemotaxis will be divided into component parts and examined individually. First, determine how activated platelets modify DBP by focusing on the most likely alteration: extracellular phosphorylation by ubiquitous protein kinases. Second, investigate how modified DBP interacts with cells by examining binding and shedding on the cell surface. Third, determine how cells terminate the cochemotactic signal by focusing on dephosphorylation by phosphatases. Finally, clinical samples from patients with inflammatory disorders will be analyzed using a proteomic approach to determine if modified DBP is correlated with disease outcome. This study will bridge basic knowledge derived from in vitro biochemical approaches and apply it to examine samples obtained from patients with inflammatory disorders. Results of this study will demonstrate a novel mechanism for a chemotactic cofactor and could serve as a prototype for other cofactors yet to be discovered. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen
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Project Title: MECHANISMS OF CHONDROCYTE RESPONSE TO MECHANICAL STIMULI Principal Investigator & Institution: Grodzinsky, Alan J.; Professor and Director; Electrical Engr & Computer Sci; Massachusetts Institute of Technology Cambridge, Ma 02139 Timing: Fiscal Year 2001; Project Start 30-SEP-1998; Project End 31-AUG-2003 Summary: Recent data suggest that there are multiple regulatory pathways by which chondrocytes sense and respond to mechanical stimuli, including upstream signaling pathways and mechanisms that may lead to direct changes at the level of transcription, translation and post-translational modifications, and cell-mediated extracellular assembly and degradation of matrix. Correspondingly, there may be multiple pathways by which physical stimuli can alter not only the rate of matrix production, but the quality and functionality of newly synthesized proteoglycans, collagens, and other molecules. In this manner, specific mechanical loading regimes may either enhance or compromise the ultimate biomechanical function of cartilage. We propose to (1) Quantify the effects of static, dynamic, and injurious compression on the morphology of intracellular organelles within chondrocytes of cartilage explants; (2) Quantify the effects of static, dynamic, and injurious compression on changes in the intracellular localization and activity of chondroitin 6-0-sulfotransferase (C6ST) transfected into primary bovine chondrocytes that are seeded into alginate gel disks subjected to compression; (3) Determine the effects of graded levels of injurious strain and strain rate on cell viability; on mRNA levels for aggrecan, collagen types I, IIA, IIB, and selected matrix metalloproteinases; on changes in morphology of intracellular organelles; and on cell-level spatial profiles of matrix turnover, and (4) Quantify the biosynthetic response of human cartilages to static, dynamic and injurious compression, using tissue from the distal femur, tibial plateau, and talocrural joint surfaces, and identify biosynthetic and degradative responses at the tissue and cell levels as a function of tissue age, location, and position. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen
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Project Title: MECHANISMS OF NERVE GROWTH CONE TURNING AND BRANCHING Principal Investigator & Institution: Letourneau, Paul C.; Professor; Cell Biology and Neuroanatomy; University of Minnesota Twin Cities 200 Oak Street Se Minneapolis, Mn 554552070 Timing: Fiscal Year 2001; Project Start 01-SEP-1985; Project End 31-MAR-2002 Summary: A growth cone is the motile tip of a growing axon or dendrite. The proper development of neural circuits depends on the pathfinding activities of growth cones. Five behaviors of growth cones are critical in the formation of neural circuits: growth cone migration, turning, branching, retraction and synaptogenesis. Proper axonal pathfinding activities are important for repair of damage to neural circuits. The hypothesis presented here is that a growth cone is a sensory-effector machine that detects environmental cues and responds by regulating these five behaviors. Growth cone migration will be studied in two specific aims: 1. Chick embryo DRG neurons will be cultured on substrata containing alternating stripes of fibronectin (FN) and chondroitin sulfate proteoglycan (CSPG), which induces growth cones to turn away from the CSPG surface. Stable and dynamic microtubules, actin filament bundles and proteins of focal contacts will be localized. The distributions of these components will be related to growth cone behaviors at the CSPG border, resulting in turning away from
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this substrate. The turning of DRG growth cones toward a positive guidance cue, NGF, presented on 10ym diameter polystyrene beads, will also be examined. Stable and dynamic microtubules and actin filament bundles will be localized, and the distributions of these components related to growth cone behaviors after contact with an NGF-bead. The NGF receptor that mediates this response will be identified, and the cytoplasmic messenger system that may be involved in growth cone turning toward a point source of NGF will be probed. To precisely examine the temporal relationship between microtubule dynamics and growth cone migration, rhodamine-conjugated tubulin will be injected into neurons to visualize individual microtubules in living growth cones as they turn at a CSPG border and as they contact NGF-beads. 2. When DRG growth cones are exposed to 20 mMCa++, there are spikes in [Ca++]i and an inhibition of growth cone migration. Experiments will determine whether the actin filament content of growth cones is reduced after [Ca++]i spikes. To probe the role of the actin-binding protein gelsolin in the disassembly of actin filaments, neurons from the gelsolin mutant mouse will be cultured, and neurons will be exposed to 20 mM Ca++, which induces [Ca++]i spikes. To further examine the roles of several Ca++-regulated proteins, gelsolin, calcineurin, and N-type Ca++ channels will be localized in DRG growth cones at the ultrastructural level. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •
Project Title: MELANOMA METALLOPROTEINASES
PROTEOGLYCAN
AND
MATRIX
Principal Investigator & Institution: Mc Carthy, James B.; Professor; Lab Medicine and Pathology; University of Minnesota Twin Cities 200 Oak Street Se Minneapolis, Mn 554552070 Timing: Fiscal Year 2002; Project Start 01-APR-2002; Project End 31-MAR-2007 Summary: (provided by applicant) Increased expression of matrix metalloproteinases (MMPs) is associated with the progression of many tumors including malignant melanoma. The activation of MMP cascades is controlled by events at the cell surface, starting with surface expression of membrane type matrix metalloproteinases (MTMMP) and also requiring the interactions between MMPs and adhesion receptors expressed in invasive tumor cells. The progression of primary melanomas is associated with increased expression of MT1-MMP and other soluble MMPs, including MMP-2, MMP-1 and MMP-13. MT1-MMP can activate proMMP-2 gelatinase, leading to more rapid degradation of ECM components and to activation of proMMP-1 collagenase. In the current proposal, we present evidence that numerous invasive primary melanoma cells express MT3-MMP (a transmembrane MMP related to MT1-MMP). Surface expression or MT3-MMP stimulates invasion of primary melanoma cells through native type I collagen gels in vitro and leads to increased in vitro gelatinolytic activity and accelerated tumor growth following subcutaneous injections into immunocompromised mice. MT3-MMP mediated invasion requires both MMP-2 and MMP-1, suggesting that MT3-MMP initiates an MMP activation cascade at tumor cell surfaces. Finally, MT3MMP mediated human melanoma invasion requires the expression of Melanoma Cell Surface Proteoglycan (MCSP), a large transmembrane adhesion receptor associated with the vast majority of human melanomas. Inhibition of the MCSP core protein expression, or inhibiting the addition of chondroitin sulfate (CS) to newly synthesized MCSP core protein, inhibits melanoma invasion and gelatinolytic activity in these cells. MT3-MMP co-precipitates with MCSP in melanoma extracts, and this co-precipitation is dependent on the presence of CS on the MCSP core protein. Furthermore, recombinant MT3-MMP, MMP-2 and MMP-1 all bind to CS-coupled beads. These results suggest that MCSP may
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help to localize and/or activate MMP cascades on the surface of invasive melanoma cells. The current proposal has two major goals. First we will further define the relationship between surface expression of MT3-MMP and activation of proMMP-2 or proMMP-1 in melanoma invasion. Secondly, we propose to test the hypothesis that MCSP serves to bind and/or modify the activation of these three invasion-promoting proteases. Understanding chondroitin sulfate interactions with MMPs may lead to new therapies to inhibit melanoma invasion and metastasis. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •
Project Title: MICROMECHANICS OF THE AORTIC VALVE:DURABILITY TESTING Principal Investigator & Institution: Vesely, Ivan; Staff; Cleveland Clinic Foundation 9500 Euclid Ave Cleveland, Oh 44195 Timing: Fiscal Year 2002; Project Start 01-MAY-1998; Project End 30-APR-2006 Summary: (provided by applicant): Aortic valve disease is treated by replacing the diseased valve with either a mechanical or an animal tissue-based artificial heart valve. Unfortunately, neither device can provide good quality of life. Tissue engineering technologies offer the promise of a limitless supply of living tissues, such as replacement heart valves. The conventional approach to tissue engineering involves seeding cells on a biodegradable matrix, implanting it into the patient, and expecting a new valve to regrow as the matrix slowly degrades. Thus far, this approach has not been very successful because cardiovascular tissues are complex and have a low capacity for selfrepair. We have been working on an alternative approach that we think is more appropriate for the aortic valve - the fabrication of the entire leaflet microstructure in vitro from the appropriate matrix molecules. We have been able to fabricate (i) collagen fiber bundles, both straight and branched, (ii) elastin tubes and sheets, and (iii) a viscoelastic glycosaminoglycan (GAG) matrix. Such an approach to tissue engineering (i) does not require regrowth of morphologically complex tissues, (ii) provides a matrix that can withstand cardiac loads immediately upon implantation, and (iii) can be designed and fabricated using conventional engineering principles. The GAG matrix is based on divinylsulfone-crosslinked hyaluronan (hylan), the collagen fiber bundles are fabricated using directed collagen gel shrinkage, and the elastin sheets and tubes have been grown on both the hylan and the collagen fiber bundles. Our next steps are to (i) improve the fabrication process of each of these components, (ii) improve their mechanical properties, and (iii) assemble the components to produce an aortic valve cusp with the appropriate mechanical properties. To this end we will (i) make use of dynamic cell culture to increase matrix synthesis and improve the mechanical properties of our constructs, and (ii) texturize hylan gels using UV and gamma irradiation to improve cell penetration and matrix adhesion.Once the material properties of the leaflet components are improved, they will be assembled into a composite aortic valve cusp and evaluated mechanically. Through this project, we aim to demonstrate that a tissue engineered valve cusp can be fabricated by manipulating biologic molecules in vitro using conventional biochemical and cell culture methodoloaies. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen
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Project Title: MOLECULAR ANALYSIS OF PFEMP1 BINDING ACTIVITY Principal Investigator & Institution: Smith, Joseph D.; Colorado State University Fort Collins, Co 80523 Timing: Fiscal Year 2001; Project Start 01-JUL-2001; Project End 31-MAY-2006
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Summary: (provided by the applicant): It is estimated that Plasmodium falciparumkills one to two million people each year. While most infections are not lethal, severe disease occurs when infected erythrocytes sequester and accumulate in vital organs, such as brain and placenta. The P. falciparumerythrocyte membrane protein 1 (PfEMP1) family has a critical role in infected erythrocyte sequestration. PftMP1 are binding ligands that are exported to the erythrocyte surface. PfEMP1 have different binding specificity and are believed to determine the anatomic distribution of infected erythrocytes and disease outcome. To explore the role of PfEMP1 in malaria pathogenesis we will study three binding traits of infected erythrocytes, adhesion to CD36, to Intercellular adhesion molecule 1 (ICAM-1), and to chondroitin sulfate A (CSA) that have been implicated in malaria disease. CD36 is the major endothelial receptor for parasite sequestration. ICAM-1 and CSA have been implicated in cerebral and placental sequestration, respectively. PfEMP1 binding domains for each of these receptors have been defined. It is estimated that each parasite strain has approximately fifty different PfEMP1. We plan to perform whole genome surveys of PfEMPI binding, with high-throughput assays, focusing on the 3D7 parasite that is the subject of the Malaria Genome Project. Findings from these investigations will assess the extent to which binding properties are encoded and conserved between HEMP 1 in a genome and will provide insight into the pathogenic potential of P. falciparum. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •
Project Title: MOLECULAR FIBRONECTIN
MECHANISMS
IN
METASTASIS--ROLE
OF
Principal Investigator & Institution: Furcht, Leo T.; Professor and Head; Lab Medicine and Pathology; University of Minnesota Twin Cities 200 Oak Street Se Minneapolis, Mn 554552070 Timing: Fiscal Year 2001; Project Start 01-APR-1977; Project End 31-DEC-2002 Summary: (adapted from the investigator's abstract) Cell adhesion is a fundamental consideration in tumor cell metastasis. Understanding the molecular basis of cellular recognition and adhesion could lead to novel forms of therapeutic intervention. Their research focus has been to understand a role for cell surface proteoglycan in modulating integrin-mediated tumor cell adhesion. As a model system, they have identified a role for cell surface chondroitin sulfate proteoglycan (CSPG) in modulating the function of alpha4beta1 integrin on melanoma cells. alpha4beta1 integrin can mediate tumor cell arrest in the vasculature due to its ability to bind to fibronectin and to VCAM, which is expressed on the surface of cytokine-activated endothelial cells. This integrin also modulates protease production and tumor cell invasion. Removal of cell surface chondroitin sulfate reduces alpha4 beta1 integrin mediated melanoma adhesion and ligand binding, suggesting that cell surface CSPG can affect the affinity state of the integrin. Furthermore, cell surface CSPG also affects alpha4 beta1 integrin-mediated cell spreading and focal contact formation by modulating intracellular signaling pathways. Collectively, the results suggest a model in which cell surface CSPG can enhance the function of alpha4 beta1 integrin by both direct and indirect interactions. To begin to test this model, they have synthesized several synthetic peptides from the extracellular domain of the alpha4 integrin subunit that could serve as potential integrin/proteoglycan binding sites. One synthetic peptide, termed SG-1, as well antiSG-1 antibodies, will inhibit alpha4 beta1 integrin-mediated cell adhesion. Furthermore, the SG-1 peptide binds cell surface CSPG by affinity chromatography, suggesting that it may inhibit alpha4 beta1 integrin function by interferring with direct interactions between alpha4 beta1 integrin and cell surface CSPG. Preliminary evidence also
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suggests that the two recpetors may constitutively associate at low levels on the cell surface, and that this association may be enhanced in the process of cell adhesion to ligands that bind both CSPG and alpha4 beta1 integrin. In this proposal, they will therefore evaluate the mechanisms by which cell surface CSPG functionally enhances alpha4 beta1 integrin-mediated adhesion and spreading and they will determine if this enhancement is due, in part, to a direct association of the two cell surface receptors. They believe that this may be representative of a more generalized mechanism of integrin-mediated cell adhesion. The overall goal in these studies is to define the molecular mechanisms that regulate CSPG/alpha4beta1 integrin interactions and to evaluate their importance in tumor cell adhesion, invasion and metastasis. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •
Project Title: MOLECULAR STUDIES OF CORNEAL TRANSPARENCY Principal Investigator & Institution: Hassell, John R.; Professor & Director; Biochem and Molecular Biology; University of South Florida 4202 E Fowler Ave Tampa, Fl 33620 Timing: Fiscal Year 2001; Project Start 01-APR-1989; Project End 31-MAR-2004 Summary: The cornea provides transparency, refraction and tensile strength, properties necessary for vision. Most of these properties are due to the unique structure of the extracellular matrix of the stroma. This matrix consists primarily of collagens I, V, & VI and of proteoglycans bearing keratan sulfate (KS) and chondroitin/dermatan sulfate side chains. The arrangement of collagen fibrils in this matrix, their small, uniform diameter and spacing, produces the transparency of the corneal stroma. cDNA cloning has identified lumican as one of the major KS containing proteoglycans of the stroma. The core protein of lumican has been shown to regulate collagen fibril diameter in vitro and the presence of its KS side chains has been shown to correlate with transparency. The long-term goals of this project are to define the interaction of the proteoglycans with collagen and identify the elements that regulate proteoglycan production. The first aim is to identify the specific structural elements on lumican that interact with the collagen by producing mutagenized recombinant lumican and testing its ability to inhibit collagen fibril growth. This aim also proposes to identify the sites on lumican that receive KS by isolating and amino acid sequencing trypsin fragments containing KS. The second aim is to search for other lumican- like proteoglycans of the cornea by screening cDNA libraries prepared from embryonic and from adult corneas. The third aim is to characterize the expression and routing of the KS sulfotransferases that regulate the maturation of the KS containing proteoglycans by preparing antibodies to the sulfotransferases and using these antibodies, in combination with antibodies to the proteoglycans, to study their rates of synthesis and their routing through the Golgi. The fourth aim is to identify the genetic elements that regulate lumican mRNA production by inserting lumican genomic DNA in reporter plasmids and testing for promoter activity by transfection into corneal fibroblasts. The fifth aim is to determine if macular corneal dystrophy type I involves defective sulfotransferases or defective lumican gene by assaying serum for sulfotransferase levels and conducting linkage studies with the lumican gene. This information will serve as a basis for understanding the mechanisms by which corneal transparency is constructed and maintained and will also provide a basis for the eventual development of new therapeutic approaches for the treatment of corneal stromal opacities. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen
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Project Title: N-ACETYLGLUCOSAMINE TREATMENT OF OSTEOARTHRITIS Principal Investigator & Institution: Okumu, Franklin W.; Optimer Pharmaceuticals, Inc. 10110 Sorrento Valley Rd, Ste C San Diego, Ca 921211643 Timing: Fiscal Year 2003; Project Start 15-SEP-2003; Project End 31-AUG-2004 Summary: (provided by applicant): Osteoarthritis (OA) represents the most common joint disease, affecting approximately 40 million Americans. OA is a leading cause of severe activity limitations and disability. Therapies that definitively alter the course of the disease are not available. Pharmacologic management of OA is limited to pain control. Nonsteroidal anti-inflammatory drugs are widely used but are associated with significant adverse reactions. Oral glucosamine and chondroitin sulfate are consumed by a large number of patients. Although some studies suggest that this reduces the rate of joint space narrowing, this conclusion is not uniformly accepted. Viscosupplementation with hyaluronan acid or its derivatives has been approved as a therapy for patients with knee OA and clinical experience demonstrated excellent patient compliance. This establishes the need for second-generation products with improved efficacy towards symptom control and disease modification. The key advantage of intraarticular therapy is in the delivery of high local drug concentrations and a reduced risk for systemic adverse reactions. The following proposal is based on prior research to identify novel effective and safe approaches to this form of OA therapy. We observed chondroprotective activities of the glucosamine derivative,Nacetylglucosamine (GIcNAc). Intraarticular injections of aqueous solutions of GIcNAc in 6 rabbits with experimental OA demonstrated greater efficacy than hyaluronan in reducing not only joint inflammation but also cartilage degradation. Adverse reactions were not observed. Based on these findings we propose the hypothesis that intra articular administration of GIcNAc represents a novel, effective and safe approach to chondroprotection. The following aims will address this hypothesis: 1. Prepare formulations of GIcNAc and retention time in rodent joints. 2. Assess therapeutic efficacy of GIcNAc formulations in rabbits with experimentally induced OA. These studies have the potential to provide the basis for a safe and effective chondroprotective therapy for OA. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen
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Project Title: PATHOGENESIS OF RADIATION-INDUCED KIDNEY INJURY Principal Investigator & Institution: Robbins, Michael E.; Professor and Section Head, Radiation Bi; Radiation Research Laboratory; University of Iowa Iowa City, Ia 52242 Timing: Fiscal Year 2001; Project Start 01-MAY-1997; Project End 31-AUG-2001 Summary: The objective of the proposed research is to define the pathogenic role that specific glomerular (ie., mesangial cells [MCs]) and tubular (i.e., tubule epithelial cells [TECs]) cells and the renin-angiotensin system (RAS) play in radiation induced kidney injury. We hypothesize that i] renal irradiation results in alterations in MC and TEC phenotype that lead to activation of the intra-renal RAS. Specific aim (SA) 1 will test the hypothesis that radiation and/or Ang II lead to modulation of gene products associated with ECM accumulation and degradation, in part, by signaling mechanisms involving reactive oxygen species (ROS). We will determine if treating MCs and TECs with radiation, Ang II and other ROS generators in vitro leads to modulation of plasminogen activator inhibitor-1 (PAI-1), tissue inhibitor of metalloproteinases-2 (TIMP-2) matrix metalloproteinase-2 (MMP-2), TGF-B and angiotensinogen (AGT, precursor of Ang II). We also will test whether addition of antioxidants or transfection with antioxidant enzymes blunts the radiation-and ANG II-induced modulation of these various gene
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products. Further, we will determine if the radiation-induced upregulation of PAI-1, MMP-2, TIMP-2, TGF-B and AGT expression observed in renal cells involves activation of the redox regulated transcription factors AP-1, AP-2 or NF-kB. The ability of Ang II to alter renal cell phenotype via ROS generation also will be studied. SA 2 will study the potential role of a glomerular-based intra-renal RAS by using adenovirus-based techniques to overexpress AGT in rat MCs. Using these transfected cells we will determine if overexpression of AGT can alter radiation-induced changes in MC expression of PAI-1, TIMP-2, MMP-2, and TGF-B. In addition, we will administer AGT transfected MCs to rat kidney glomeruli in vivo, to modulate intra-renal generation of Ang II in the irradiated kidney. SA 3 will use a unique double transgenic model produced by breeding mice that express human AGT only in proximal convoluted TECs with mice expressing human renin. Resultant double transgenics exhibit increased intrarenal Ang II synthesis; systemic levels are unaffected. Human AGT expression is androgen-dependent; expression in females is dependent on exogenous androgen administration. We will determine if irradiating kidneys of male double transgenic mice leads to increased ECM accumulation and exacerbation of functional and morphologic injury. Female mice will be used to investigate the temporal aspect of intra-renal RAS by administering androgens at various times/periods after irradiation. These studies offer the promise of developing rational therapeutic strategies directed at reducing the severity of this dose-limiting morbidity in human beings. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •
Project Title: PERLECAN AND CHONDROGENESIS Principal Investigator & Institution: Carson, Daniel D.; Trustees Distinguished Professor and Cha; Biological Sciences; University of Delaware Newark, De 19716 Timing: Fiscal Year 2001; Project Start 01-APR-2001; Project End 31-MAR-2005 Summary: (Adapted from the Investigator's Abstract): Embryonic cartilage formation or chondrogenesis is an early process of mesenchymal conversion leading to the formation of skeletal structures. Precursor cells are recruited into a condensing core that, in turn, differentiates into chondrocytes. This differentiation process is accompanied by the elaboration of characteristic cartilage marker proteins such as collagen II and the chondroitin sulfate proteoglycan, aggrecan. Subsequently, chondrocytes undergo hypertrophic growth, a phase in which they express other marker proteins, including collagen type X and alkaline phosphatase. Molecular controls over chondrogenesis are manifest at many levels including the expression of key growth factors/cytokines and transcription factors. In addition, several lines of evidence indicate that heparan sulfatebearing molecules of the extracellular matrix appear to promote chondrogenesis. Recently it has been reported that the expression of the heparan sulfate proteoglycan, perlecan, in both embryonic and adult cartilage. Moreover, targeted disruption of the perlecan gene results in abnormal cartilage development in mice. Our lab has found that perlecan rapidly and efficiently induces chondrogenesis in multipotential mouse embryonic fibroblasts and maintains the chondrogenic phenotype of adult human chondrocytes in vitro. This activity appears to be dependent upon both the heparan sulfate and protein constituents of perlecan. Taken together, these studies suggest that perlecan plays an important role in the cascade of events required for cartilage formation and orderly differentiation. We suggest that perlecan provides an organizational matrix that helps coordinate chondrogenesis. The proposed studies will explore the molecular basis of the action of perlecan in the promotion of chondrogenesis. Possibilities include growth factor concentration and presentation, modulation of cell adhesion and alteration of signal transduction cascades and gene
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expression. Implicit in all of these non-exclusionary possibilities is the interaction of perlecan, alone, or in a complex with one or more cell surface receptors. It is also unclear if perlecan can cooperate with growth factors to drive precursor cells through the complete program of chondrogenesis in vitro and in vivo. We will use a variety of cell biological, biochemical and molecular biological techniques to define the structurefunction relationship between perlecan domains and chondrogenic activity. As model system, we will use multipotential mouse chondrogenic precursor cells and maintenance of the chondrogenic phenotype in human normal and exostoses-derived chondrocytes. These studies provide novel opportunities to use perlecan or perlecan fragments as inducers of chondrogenesis for design of therapeutic strategies to replace damaged or surgically-removed cartilage. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •
Project Title: RECEPTORS
PILOT--INVASION
REGULATED
BY
FIBRONECTIN
AND
Principal Investigator & Institution: Kapila, Yvonne L.; University of California San Francisco 500 Parnassus Ave San Francisco, Ca 94122 Timing: Fiscal Year 2001; Project Start 01-JUN-2001; Project End 30-NOV-2005 Summary: The extracellular matrix is an important regulatory component of tumor cell invasion and migration. Specifically, the alternatively spliced V region of fibronectin (FN) is important to these progresses since only FN miniproteins (V+H and V+H-) containing this region induce increased invasion and migration of squamous cell carcinoma (SCC) cells in vitro. In contrast, primary normal keratinocytes and fibroblasts undergo apoptosis when treated with the V+H-FN protein. In fibroblasts, this mechanism is mediated by chondroitin sulfate proteoglycans, possibly by the alpha 4 integrin, by a caspase cascade involving caspase-1 and -3, by alterations in p53 and cmyc, and by a concomitant decrease in pp125 FAK. These data suggest that tumorigenicity has enabled SCC cells to bypass the apoptotic pathway and instead take on an invasive and migratory phenotype in response to the V+H- protein. It is hypothesized that SCC cells undergo increased migratory phenotype in response to the V+H- protein. It is hypothesized that SCC cells undergo increased invasion and migration in response to the alternatively spliced V region of FN via cell surface proteoglycan and integrin receptors, which initiate a signal transduction pathway that differs from that in primary non- transformed receptors, which initiate a signal transduction pathway that differs from that in primary non-surface receptor(s) involved in mediating increased migration and invasion induced by the V-containing FN fragments. Specifically, determine whether condroitin sulfate proteoglycans and the alpha4 integrin are involved in this mechanism of invasion and migration, since these receptors regulate the apoptotic pathway triggered by the V-containing FN fragment in fibroblasts. (2) Examine the SCC cell signaling response involved in mediating increased migration and invasion induced by the V-containing FN fragments. Specifically, determine whether p53 and c-myc are modulated as in the primary cells. These studies will help explain some of the basic mechanisms underlying the cell-matrix interactions and signaling mechanism that regulate tumor cell biology. In addition, since squamous cell carcinoma is the most common type of malignant oral neoplasm, accounting for a major portion of deaths related to oral cancer, these studies may provide potentially useful avenues for therapeutic intervention. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen
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Project Title: GLUCOSAMINE
PILOT--MANAGING
OSTEOARTHRITIS
SYMPTOMS:
Principal Investigator & Institution: Yoon, Saun-Joo L.; University of Florida Gainesville, Fl 32611 Timing: Fiscal Year 2001; Project Start 01-AUG-2001; Project End 31-JUL-2004 Summary: (from applicant's Abstract) In the millennium, the health care system in the United States will be forced to focus on managing chronic illness and preventing disability in the increasing aging population. Osteoarthritis (OA), particularly of the knee and hip, is the most common chronic condition and the leading cause of disability among older adults. Current treatment regimens either provide only temporary relief with medications or require surgical intervention. Such treatments can be costly in terms of adverse effects and rehabilitation. In addition, more people are spending money to obtain dietary supplements to manage their symptoms related to OA and other chronic illnesses, Although glucosamine and chondroitin sulfate (GCS) has shown some effectiveness in relieving arthritic pain, its use has not been supported by the American College of Rheumatology. The purpose of this study is to determine if oral GCS results in functional, global, and structural improvement. The proposed study is a randomized, double-blinded, and placebo-controlled study with repeated measures. The sample will consist of twenty persons 50 years and older with osteoarthritis in at least one knee. Subjects in experimental and control groups will receive GCS and a placebo, respectively, for six months. Subjects in both groups will be provided with placebo for the 3 months until follow-up assessment to prevent them from crossing over. Dependent measures include: 1) range of motion, gait balance, and strength of the affected knee joint for measuring functional improvement; 2) severity of osteoarthritis, pain distress, and quality of life for measuring global improvement; and 3) MRI of the knee for measuring structural improvement. This study fills an important gap in our knowledge about the effect of glucosamine and chondroitin sulfate and may show effects that will impact intervention in persons with OA in the future. In particular, the proposed study will provide nurses with the data necessary to determine whether or not to recommend GCS as a treatment for their patients with OA. If GCS successfully decreases pain and slows down the joint degenerating process, OA patients may be more likely to comply with non-pharmacological treatments such as exercise. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •
Project Title: PREVENTION OF HIP DYSPLASIA WITH THERMAL ENERGY Principal Investigator & Institution: Lopez, Mandi J.; Medical Sciences; University of Wisconsin Madison 750 University Ave Madison, Wi 53706 Timing: Fiscal Year 2001; Project Start 01-SEP-2001; Project End 31-JUL-2006 Summary: The fundamental goals of this research proposal are to test the hypotheses that: 1) application of thermal energy at 65 degrees C using radio-frequency energy to the coxofemoral joint capsule of puppies with radiographic evidence of joint laxity will result in normal hip congruity, 2) will prevent the development of the lameness and the cartilagenous and bony changes characteristic of CHD, and 3) will not have detrimental effects on the biomechanical or viscoelastic properties of the joint capsular tissue. These investigations will yield insights into the fundamental mechanisms of thermal modification of musculoskeletal soft tissue. This research program is designed to determine whether thermal modification of coxocofemoral joint capsule of 16-week-old puppies with excessive joint: laxity will prevent CHD. Ultimately, this model will serve to evaluate the potential of thermal energy to reduce excessively lax coxofemoral joints
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in neonatal children and thereby help prevent DDH. The candidate of this application graduated magna cum laude from Humboldt State University with a B.S. in cellularmolecular biology and a minor in chemistry. She worked as a molecular biologist at Amgen, Thousand Oaks, CA, before undertaking and; completing her D.V.M. at the University of California-Davis. Dr. Lopez was awarded 5 scholarships and 2 research grants while a D.V.M. student. She completed an internship at Kansas State University and a large animal surgery residency/Master's degree at they University of WisconsinMadison. She is a board certified large animal surgeon. Dr. Lopez's Master's thesis was entitled "Effects of Radio-frequency Energy on Ovine Stifle Joint Capsule", and she performed much of the early radio- frequency work in the Comparative Orthopaedic Research Laboratory. She was awarded an NRSA in 1998 and has performed the background research and preliminary, studies that form the basis for this proposal. She passed her preliminary examinations "With Honors" in November, 1999, and is scheduled to complete her PhD in June 2001. Her ultimate goal is to join the faculty of an academic institution as a well-trained scientist and productive researcher specializing in integrative, translational research. The training environment will be guided toward mentoring the candidate while teaching valuable research techniques necessary to begin an independent research career. The majority of supervision will be provided by Mark D. Markel, an internationally known and respected investigator in the area of thermal tissue modification, Professor of Surgery, and Professor and Chairman of Medical Sciences. The advisory committee will consist of well-respected and highly experienced individuals within the University. The Comparative Orthopaedic Research Laboratory is a well established laboratory that houses multi- disciplinary research programs. The University of Wisconsin provides an exceptional environment for interaction with experts in a variety of fields, and it is well known for its exceptional research programs, especially in the medical sciences. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •
Project Title: PROBING SINGLE-MOLECULE NEURON-LIGAND PATHFINDING Principal Investigator & Institution: Beebe, Thomas P.; Professor and Director of Surface Analys; Chemistry and Biochemistry; University of Delaware Newark, De 19716 Timing: Fiscal Year 2001; Project Start 20-SEP-2001; Project End 31-AUG-2004 Summary: Among the most debilitating and costly human ailments are injuries and diseases of the nervous system. They affect millions of people in the US and represent a large part of the total national health care cost. Currently there are a limited number of available therapies, none of which restore function to injured neurons of the CNS. Research efforts from a variety of areas are offering real hope for improving the clinical outcome of these conditions. Numerous studies in animals and man strongly suggest that restorative therapies based on cell transplantation are feasible. However, a major challenge that remains is the reconstruction of damaged and diseased neural pathways. Toward this end, biomaterials have been examined as bridging devices to support directed nerve outgrowth from regenerating neurons. One of the fundamental challenges involves understanding how to engineer the surface of such biomaterial bridges. This revised Bioengineering Research Partnership (PAS- 00-006) project is driven by the central hypotheses that the local surface density, conformation and discrete spatial distribution of substrate molecules are sensed by a neuron's integrin receptors, translated in an intracellular molecular sequence that regulates integrin receptor expression and controls further axonal growth and also determines the overall readiness of the neuron to regenerate and establish connections. This partnership will bring together the expertise of a surface analytical chemist (Beebe) possessing a
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background in bond- rupture force measurements, surface modification, and state-ofthe-art surface analytical techniques, with the expertise of a biophysics-oriented bioengineer (Hlady) possessing a background in protein-surface interactions, evanescent wave optics, time- resolved fluorescence spectroscopy, scanning probe microscopy and a complementary set of state-of-the-art surface analytical techniques and a neuroscienceoriented bioengineer (Tresco) possessing a background in tissue engineering, nervous system repair and biomaterials. The three specific aims are to: (1) create and fully characterize model substrates with a controlled pattern and surface density of laminin, fibronectin and related oligopeptides for neuron and astrocyte attachment and axonal growth studies in the two other Aims; (2) Study neurite outgrowth (dynamic bond strength, diffusivity, surface density and bond-rupture force) of dorsal root ganglion neurons on the model substrates, employing single- molecule techniques such as AFM bond-rupture measurements and fluorescence correlation spectroscopy; (3) Study the axonal growth of neurons (dynamic bond strength, diffusivity, surface density and bond-rupture force) on confluent astrocyte monolayers of different ages, using the same methodologies. Underpinning all studies are extensive quantitative surface characterization techniques. The advent and maturation of the methodologies used in single- molecule bond-rupture and single-molecule fluorescence measurements have allowed the direct and highly controlled measurement of protein-ligand, proteinprotein, and protein- surface interactions on an individual, molecule-by-molecule basis. Similar ligand-receptor studies (i.e. binding-force measurements complemented with single-molecule fluorescence experiments) will be extended to the study of molecules involved in the guidance of neuron growth cones and axons. This molecular understanding of the balance between specific and non-specific ligand-receptor interactions will be supplemented with microscopy studies (fluorescence and atomic force) of axon development on ligand-modified substrates. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •
Project Title: PROTEOGLYCANS IN DIABETIC NEPHROPATHY Principal Investigator & Institution: Mccarthy, Kevin J.; Associate Professor; Pathology; Louisiana State Univ Hsc Shreveport P. O. Box 33932 Shreveport, La 71103 Timing: Fiscal Year 2002; Project Start 01-MAY-1994; Project End 30-APR-2006 Summary: This abstract is not available. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen
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Project Title: PROTEOGLYCANS IN NORMAL AND SCARRED CORNEAS Principal Investigator & Institution: Funderburgh, James L.; Associate Professor; Ophthalmology; University of Pittsburgh at Pittsburgh 350 Thackeray Hall Pittsburgh, Pa 15260 Timing: Fiscal Year 2002; Project Start 01-AUG-1993; Project End 31-JUL-2007 Summary: (provided by applicant): Corneal scars exhibit a disruption of stroma collagen fibril diameter and spacing that contributes to loss of transparency. These alterations are closely associated with changes in stromal glycosaminoglycans, acidic polysaccharides that form bridges between adjacent collagen fibrils. This project will examine the hypothesis that altered transcription of genes involved in elongation and sulfation of glycosaminoglycans generates the abnormal glycosaminoglycans of scar tissue and is directly responsible for disruption of stromal transparency. In the past two years genes coding for the enzymes involved in elongation and sulfation of corneal glycosaminoglycans have been identified. At the same time, we have developed and
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characterized cultures of primary keratocytes that maintain a glycosaminoglycan expression profile similar to that of normal cornea but which can be stimulated to secrete glycosaminoglycans resembling those of scar tissue. These developments present the opportunity to directly test the role of glycosaminoglycans in stromal transparency. We will address the hypothesis in three stages: (1) Identify the genes involved in generating normal and fibrotic stromal glycosaminoglycans. (2) Demonstrate that altered glycosaminoglycan biosynthesis results from transcriptional regulation of biosynthetic genes under the control of gene-specific promoter sequences. (3) Characterize the effects of corneal-specific overexpression of chondroitin sulfotransferase and synthase in vivo. This third aim will generate transgenic mice in which corneal chondroitin sulfate overexpression is inducible. Corneal transparency cellularity and collagen fibril organization of the mice will be documented. Together these three aims will establish which genes are involved in mediating the corneal glycosaminoglycan phenotype and how these genes are controlled, and will show that inappropriate expression of these genes leads to tissue changes similar to those in scars. These experiments will link the long held idea of the importance of glycosaminoglycan in corneal transparency with the expression patterns of specific genes. These results may be relevant to development of therapeutic approaches in the cornea as well as other tissues. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •
Project Title: PROTEOGLYCANS/MATRIX ASSEMBLY IN REGENERATING CARTILAGE Principal Investigator & Institution: Oegema, Theodore R.; Professor and Chair; Orthopedic Surgery; University of Minnesota Twin Cities 200 Oak Street Se Minneapolis, Mn 554552070 Timing: Fiscal Year 2001; Project Start 25-FEB-2000; Project End 31-JAN-2004 Summary: (adapted from applicant's abstract) Proteoglycans (PG) are recognized as important constituents of the mechanical properties of cartilage. However, the possibility that PG influence matrix quality by regulating cell functions has not been examined in detail and mechanisms of matrix assembly have not been examined. These processes are important for cartilage engineering and the proposal will establish the effect of PG on the assembly of neocartilage matrix and to use artificial polymers to direct this effort. The applicants have developed a rabbit articular chondrocyte culture model that allows biochemical, metabolic, morphological and biomechanical analyses. With this model it was demonstrated that polyethylene glycol as a surrogate for aggrecan to control osmotic pressure and exclude volumes increased PG synthesis and matrix content. The proposed studies will (1) test the hypothesis that the effect of exogenous aggrecan on matrix synthesis during the critical phase of matrix accumulation by cultured chondrocytes is due only to the osmotic properties of aggrecan; (2) determine how the structure of aggrecan or aggrecan substitutes promote assembly; (3) determine whether aggrecan promotes matrix assembly during the critical transitional phase by providing physical-chemical properties and not structural properties; (4) examine whether in the presence of adequate aggrecan the diameter of the collagen fibril will control the effectiveness of the collagen network in retaining aggrecan. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen
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Project Title: PTHRP 1 TO 173 IN CHONDROCYTES Principal Investigator & Institution: Terkeltaub, Robert A.; Veterans Medical Research Fdn/San Diego Foundation of San Diego San Diego, Ca 92161 Timing: Fiscal Year 2001; Project Start 06-APR-2001; Project End 31-JAN-2006 Summary: (Verbatim from the Applicant): Parathyroid hormone related protein (PTHrP) is required for endochondral development and critically regulates growth plate cartilage organization and mineralization. We have discovered that articular cartilage PTHrP expression becomes robust in osteoarthritis (OA) but that chondrocytes preferentially express the least widely expressed PTHrP isoform (PTHrP 1-1 73). PTHrP isoforms are endoproteolytically cleaved to generate biologically active peptides. Moreover, the unique C-terminal 140-173 domain peptide of PTHrP 1-173 determines marked effects on chondrocyte matrix synthetic function and the elaboration of PPi (a major regulator of chondrocyte mineralization) by an intracrine mechanism. We will test the hypotheses that the 147-150 KKKK motif of PTHrP 1-173 modulates both endoproteolytic processing and the subcellular and nuclear localization of PTHrP 1-173. We also hypothesize that PTHrP 1-173 processing at the 147-150 motif critically regulates chondrocyte synthetic and mineralizing functions. To test these hypotheses, we will identify the peptides derived from PTHrP 1-173 by endoproteolysis in cultured articular chondrocytes and chondrocytic TC28 cells. We also will identify the molecular mechanism by which chondrocytes process proPTHrP 1-173 at the N-terminus to derive active PTHrP, and process the 147-150 KKKK motif to affect the biologic activity of PTHrP 1-173. In doing so, we will test the hypothesis that furin-like subtilisin family proprotein convertases (PCs) are at least partially responsible. Methods employed in these studies will include physical and immunochemical approaches to characterize PTHrP 1-173 derived peptides in cultured chondrocytes and a genetic screening approach for cleavage site-specific endoproteases. Having defined how chondrocytes process PTI-IrP 1-173, and the peptides generated, we will determine how the Cterminal processing products affect chondrocyte functions. We will focus on growth, collagen synthesis, PPi elaboration and mineralization. We also will test the hypothesis that a nuclear localization signal (NLS) at the 147-150 domain of PTHrP 1-173 is critical for certain regulatory effects of PTHrP 1-173 on chondrocyte functions. To do so, we will permeabilize chondrocytes and treat with labeled wild-type and mutant forms of PTHrP 1-173, and PTHrP 140-173. Last, we will directly test the hypothesis that PTHrP 1-173 modulates hydroxyapatite and CPPD crystal deposition by cultured chondrocytes. Completion of these studies will indicate not only how PTHrP 1-173 can modulate OA, but also how functional properties of the PTHrP 1-173 C-terminal 140-173 domain can be harnessed to promote cartilage repair. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen
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Project Title: REGULATION OF AGGRECAN CATABOLISM Principal Investigator & Institution: Hering, Thomas M.; Associate Professor; Orthopaedics; Case Western Reserve University 10900 Euclid Ave Cleveland, Oh 44106 Timing: Fiscal Year 2001; Project Start 01-AUG-2001; Project End 31-MAY-2006 Summary: (provided by applicant): Aggrecan is a large hybrid proteoglycan of the cartilage extracellular matrix, which is critical to cartilage functional properties. The interglobular domain (IGD) in mammalian aggrecan contains aggrecanase and matrix metalloproteinase cleavage sites, and additional sites for aggrecanase-mediated cleavage have been described in the CS-2 domain. We have constructed the first full-sized aggrecan expression vector to surmount the limitations of smaller aggrecan subdomain
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constructs used previously as mutagenizable aggrecanase substrates. We propose the hypothesis that highly conserved proteinase cleavage sites in aggrecan are important in regulation of aggrecan turnover. We further hypothesize that the chondrocyte can regulate aggrecan catabolism by altering glycosylation patterns on the aggrecan substrate. To address these hypotheses, we propose the following Specific Aims: Specific Aim 1: To determine amino acid residues required for recognition and cleavage by aggrecanase. Comparison of known aggrecanase cleavage sites in aggrecan and brevican have revealed conservation of clusters of flanking residues. We will establish whether these flanking residues are required for cleavage by aggrecanase by replacing conserved residues and assaying for cleavage at each site. Specific Aim 2: To determine the functional relationships between cleavage sites in aggrecan. Cleavage at the MMP site in the IGD has been shown to inhibit aggrecanase cleavage within the IGD, suggesting the involvement of motifs in the G1 domain in aggrecanase substrate recognition. We will mutagenize these G1 motifs and assay for aggrecanase cleavage at the IGD site. There is also evidence that cleavage of aggrecan C-terminal sites precedes, and may be a prerequisite for cleavage within the IGD. We will mutagenize aggrecanase sites within the CS-2 domain and determine directly whether cleavage at the IGD is inhibited. Specific Aim 3: To determine whether susceptibility to aggrecanase cleavage may be regulated by known and potential sites for KS substitution of aggrecan. We will determine the optimal cell type for expression of KS-containing aggrecan. We will mutagenize threonine residues in the IGD and "nodal" region of the CS-2 domain to prevent KS substitution and assay for aggrecanase susceptibility. Wild-type and mutant aggrecan constructs will be expressed in chondrocytes isolated from cartilage of different aged animals, to determine if there is an age-specific pattern of glycosylation that influences aggrecanase susceptibility. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •
Project Title: REGULATION OF FUNCTIONALLY REACTIVE GLIOSIS BY TGFBETA Principal Investigator & Institution: Mckeon, Robert J.; Assistant Professor; Cell Biology; Emory University 1784 North Decatur Road Atlanta, Ga 30322 Timing: Fiscal Year 2001; Project Start 01-SEP-1998; Project End 30-JUN-2003 Summary: The astrocytic response to CNS injury has long been implicated in the failure of damaged axons to regenerate beyond the injured area. Recent experiments have demonstrated that reactive astrocytes, originally considered physical barriers to regenerating axons produce an extracellular matrix (ECM) that inhibits axon outgrowth. In vitro assays suggest that the inhibitory component of this ECM is associated with the expression of chondroitin sulfate proteoglycans (CS-PGs) and that decreasing CS-PG expression after injury would enhance axonal regeneration through areas of reactive astrogliosis. CS-PGs are a group of complex molecules whose synthesis in a variety of peripheral cells is upregulated by transforming growth factor-beta (TGF-beta). The role of TGF-beta on CS-PG expression in the CNS is less clear. TGF-beta and CS-PG levels are highest in embryonic animals and both are downregulated shortly after birth. TGFbeta levels increase following CNS injury and this increase is correlated temporally and spatially with the re-expression of CS-PGs. Preliminary data demonstrate that in response to TGF-beta, cultured astrocytes synthesize a neurite growth inhibitory CS-PG and that this response is blocked by the addition of TGF-beta neutralizing antibodies. Data demonstrating that CS-PG expression is blocked after CNS injury by the in vivo administration of these TGF-beta neutralizing antibodies is now included. Based on these significant findings, it is hypothesized that TGF-beta stimulates CS-PG production
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after CNS injury and that neutralizing TGF-beta bioactivity will enhance axonal regeneration in vivo. These hypotheses will be tested by: ( 1 ) determining whether TGFbeta regulates the production of CS-PG after CNS injury by continuous intraventricular delivery of TGF-beta neutralizing antibodies and assessing CS-PG levels in the injured area; (2) examining the expression of specific CNS CS-PGs in response to TGF-beta, and; (3) examining whether neutralizing the function of TGF-beta enhances axonal regeneration following spinal cord injury. These studies will help identify signals that stimulate the production of axon growth inhibitory CS-PGs by reactive astrocytes. Decreasing the expression of these inhibitory molecules, combined with the use of factors known to promote axon outgrowth, may lead to the development of comprehensive strategies designed to optimize axonal regeneration after CNS injury. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •
Project Title: REGULATORY ROLES OF LACTOFERRIN IN HEMOSTASIS Principal Investigator & Institution: Wu, Haifeng M.; Pathology; Ohio State University 1800 Cannon Dr, Rm 1210 Columbus, Oh 43210 Timing: Fiscal Year 2002; Project Start 01-APR-1995; Project End 31-MAR-2004 Summary: Lactoferrin is a prominent component of neutrophil secondary granules and can be released when neutrophils are activated. The concentration of lactoferrin in blood has been demonstrated to be increased in certain inflammatory diseases. In contrast to a well described biochemical characterization of lactoferrin as an iron-binding protein, its physiological role in the regulation of inflammation and other host defense mechanisms is unclear. The current proposed study will test three hypotheses: (i) lactoferrin derived from neutrophils is an important physiological mediator in the down-regulation of blood anticoagulation; (ii) the significant elevation of lactoferrin in blood, or at sites of inflammation can contribute significantly to the development of prothrombotic sequelae as seen in the disseminated intravascular coagulation (DIC) associated with bacterial infections; and (iii) the structural determinant(s) of lactoferrin involved in heparin binding is located within a specific sequence (residues 25-31) of the N-terminus. Thus, specific aims of this proposal are: (1) to determine the relationship between the elevation of plasma lactoferrin and the development of prothrombotic complications in patients with bacterial infections. The plasma lactoferrin concentration in patients with DIC resulting from different underlying diseases or with different inflammatory diseases will be examined; (2) to define the structural determinant(s) of lactoferrin involved in heparin binding. Both site- specific and domain-replacement mutagenesis will be used to determine the contribution of N-terminal basic residues (25 to 31) in heparin binding; (3) to study the activity of lactoferrin in the regulation of protein C anticoagulant pathway. Both the effect of lactoferrin on the generation of activated protein C and the specific binding of lactoferrin to chondroitin sulfate moiety of thrombomodulin will be examined. The completion of these studies will enable us to understand the biological role of lactoferrin in the regulation of inflammation and blood coagulation, and will provide new scientific background for the clinical evaluation and management of infectious diseases with thrombotic complications. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen
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Project Title: ROLE OF PROTEOGLYCAN IN ATHEROGENESIS Principal Investigator & Institution: Hinsdale, Myron E.; Oklahoma Medical Research Foundation Oklahoma City, Ok 73104 Timing: Fiscal Year 2003; Project Start 01-SEP-2003; Project End 30-JUN-2008
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Summary: The goal of this proposal is to investigate the role of chondroitin sulfate (CS) and dermatan sulfate (DS) proteoglycan biosynthesis in atherogenesis. As an atherosclerotic lesion develops in the blood vessel wall, CS and DS proteoglycans biglycan, decorin, and versican accumulate. Because lipoproteins bind in vitro to proteoglycans and co-localize with them in the atherosclerotic lesion, it has been hypothesized that increased proteoglycan biosynthesis by cells in the vessel wall is atherogenic. Biglycan is a likely candidate proteoglycan for binding and retaining lipoproteins since it binds atherogenic lipoproteins in vitro, co-localizes with apolipoprotein B (apoB) and E (apoE) in human atherosclerotic lesions, and more closely co-localizes with apoB and apoE in mouse lesions than decorin. Furthermore, because biglycan has both protein and glycosaminoglycan (GAG)-mediated interactions with other proteins (e.g. collagens, lipoproteins, TGFbeta), we hypothesize that these interactions are important to the structure and development of the lesion in the vascular wall. To test these hypotheses our three aims focus on measuring and characterizing atherosclerosis in 3 animal models. In specific aim 1, we will determine whether increased biosynthesis of biglycan by endothelial cells can exaggerate the development of atherosclerosis. In specific aim 2, we will determine whether increased biosynthesis of biglycan by vascular smooth muscle cells can exaggerate the development of atherosclerosis. In specific aim 3, we will determine whether the GAG modifications of biglycan are important for atherosclerotic lesion development and structure. All three mouse models will be made atherogenic by crossing them to either low-density lipoprotein receptor deficient or apolipoprotein E deficient mice. Our objectives with these mouse models of atherosclerosis are to determine the roles increased biosynthesis and GAG modification of biglycan have in atherosclerotic lesion development and progression. In addition to standard atherosclerotic lesion analysis and extensive histologic characterization including immunohistochemistry for different collagen types and biglycan, intravital microscopy and magnetic resonance imaging will be used to characterize the vascular pathology in these mice. Overall, these proposed studies will more clearly define the role biglycan accumulation and biglycan GAG modification have in the pathogenesis of atherosclerosis. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •
Project Title: SEQUENCE ANALYSIS OF GLYCOSAMINOGLYCANS Principal Investigator & Institution: Sasisekharan, Ram; Associate Professor; Division of Toxicology; Massachusetts Institute of Technology Cambridge, Ma 02139 Timing: Fiscal Year 2002; Project Start 01-FEB-1998; Project End 31-JAN-2006 Summary: (provided by applicant): Sequencing of DNA and proteins has heralded a biotechnology revolution. Our ability to determine the nucleic acid or polypeptide structure with a specific biological function has enabled us to probe biological phenomenon in a mechanistic, rigorous manner and facilitated the development of novel therapeutics. However, this approach has yet to be achieved with the third major class of biopolymer, viz., polysaccharide. Complex polysaccharides of the glycosaminoglycan (GAG) family are important modulators of numerous biological processes, from development to neovascularization to maintenance of the nervous system. However, expect for a few cases, it is still unknown how GAG structures impinge on function. Only with this knowledge will it be possible to utilize the information inherent in GAGs, either scientifically or therapeutically. To this end, the principal investigator has recently developed a powerful sequencing approach for a subset of GAGs (heparan sulfate-like glycosaminoglycans or HLGAGs). One of the primary experimental constraints used in this sequencing approach is the heparinases, a
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group of polysaccharide lyases from Flavobacterium heparinum that the principal investigator has cloned and characterized. In this grant proposal, he proposes to extend the repertoire of tools for use in the sequencing approach and to probe further the biological functions of GAGs. He proposes to do this in two ways: (1) Clone and biochemically characterize other HLGAG-degrading enzymes from F. heparinum, and (2 establish a complementary sequencing approach for chondroitin/dermatan sulfate GAGs using the chondroitinases from F. heparinum. In this manner, the principal investigator hopes to broaden the knowledge of complex polysaccharides and learn how structure translates to function. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •
Project Title: SHEAR STRESS AND CHONDROCYTE GENE EXPRESSION Principal Investigator & Institution: Smith, Robert L.; Professor-Research; Functional Restoration; Stanford University Stanford, Ca 94305 Timing: Fiscal Year 2001; Project Start 15-SEP-2000; Project End 31-AUG-2004 Summary: While the precise etiology of the degenerative joint disease, osteoarthritis, is unknown, clinical manifestations of pain and disability are most often associated with inappropriate mechanical loading. As evident at surgery, focal erosion of articular cartilage culminates in loss of joint function and remains the final common pathway in all cases of osteoarthritis irrespective of cause. The goal of this study is to determine the cellular mechanisms by which mechanical loading influences cartilage matrix synthesis and degradation. In the joint, cartilage cells, chondrocytes, are subject to a complex array of stresses and strains. Our work shows that normal chondrocytes in culture react metabolically to univariate mechanical stimulation applied either as intermittent hydrostatic pressure or as fluid- induced shear stress. The hypothesis to be tested here is that distinct intracellular signaling pathways underlie the articular cartilage response to the two forms of mechanical stimulation. Fundamental knowledge exists regarding the effects of the proinflammatory cytokine, interleukin-1, on inhibition of cartilage extracellular matrix macromolecule synthesis and induction of cartilage degrading enzyme synthesis by chondrocytes. However, the effects of mechanical loading on the expression of articular chondrocyte degradative enzymes in the presence of IL-1 remain unclear. The specific aims will quantify effects of shear stress (SS) and intermittent hydrostatic pressure (IHP) on human osteoarthritic articular chondrocytes in vitro to: (1) Test the hypothesis that IHP and SS differentially modulate extracellular matrix macromolecule expression in OA versus normal chondrocytes; (2) Test the hypothesis that IHP and SS modulate IL-1beta induced inhibition of proteoglycan and type II collagen synthesis in OA and normal chondrocytes; (3) Test the hypothesis that IHP and SS alter endogenous MMPs and aggrecanase expression in OA and normal chondrocytes; (4) Test the hypothesis that IHP and SS alter IL-1beta induced expression of MMPs and aggrecanse in OA and normal chondrocytes. The expected result is that SS and IHP will show dissimilar capacities to overcome the IL-1 induced shift of chondrocyte metabolism from cartilage maintenance to matrix destruction. The results of this study will be of importance to the fields of orthopaedics, rheumatology and rehabilitation medicine. The techniques will involve analysis of proteoglycan and collagen synthesis by incorporation of radiolabeled precursors. mRNA signal levels will be quantified by Northern blotting and RT-PCR analysis. Cytokines will be quantified by bioassays and commercially available ELISA. MMPs will be identified by zymography and Western blotting and quantified by Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen
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Project Title: SKIN ADAPTATION TO MECHANICAL STRESS Principal Investigator & Institution: Sanders, Joan E.; Bioengineering; University of Washington Seattle, Wa 98195
Associate
Professor;
Timing: Fiscal Year 2003; Project Start 09-JUL-2003; Project End 30-JUN-2007 Summary: (provided by applicant): The long-term objective of this research is to develop therapies to encourage skin strengthening in individuals at risk of skin breakdown from prolonged mechanical stress (e.g. prosthesis users). The specific aims are to develop, evaluate, and use an in vitro skin model system to investigate collagen structural and bioprocess changes that occur in skin adapting to repetitive mechanical stresses, and to apply that insight to an in vivo model to test a new therapy to encourage skin strengthening. For the in vitro model, a surgically-excised pig skin sample is put in culture at an air-media interface within a custom-designed flow chamber. Clinically relevant stresses, those experienced at the residual limb-prosthetic socket interface by lower-limb amputees, are applied to the explant surface for at least a 2-week period using a custom-designed, closed-loop, force-controlled load applicator. Mechanisms of collagen adaptation are investigated to pinpoint specific biomolecules responsible for promoting the adaptive processes resulting in a mechanically stronger structure. A key question to answer is if collagen fibril diameters are increased by adding to existing fibrils or by degrading old collagen and forming new fibrils. It is hypothesized that after a metalloproteinase concentration peak to degrade small existing collagen fibrils, proteoglycans decorin, biglycan, fibromodulin, lumican, and thrombospondin-2 as well as collagen-related integrin expression are upregulated; chondroitin sulfate and collagen V are downregulated; collagen I and III production and cross-linking increase; and new larger collagen fibrils are formed. As a potential therapy to facilitate skin adaptation, a graded-increase stress-application treatment is tested using an in vivo skin model. If started before the metalloproteinase peak has subsided, the treatment is expected to create an architecturally inferior and weak tissue. However, if started after the metalloproteinase peak during remodeling, the treatment should enhance collagen fibril diameter and skin strength. Similar should be the case if the treatment is initiated during the stabilization phase of adaptation, though fibril enlargement and strength should be even further enhanced since the treatment will likely re-initiate the entire adaptation process. If shown to enhance architecture and strength, the treatment regime would have direct clinical applicability. The health relatedness of this proposal is new knowledge that has potential application to the development of novel treatments for persons at risk of skin breakdown. By understanding the process of skin adaptation (natural skin strengthening) at both a cellular and molecular level, therapies to encourage skin adaptation before breakdown occurs can be intelligently pursued. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •
Project Title: SMALL LEUCINE RICH PROTEOGLYCANS AND ATHEROGENESIS Principal Investigator & Institution: Williams, Kevin J.; Columbia University Health Sciences New York, Ny 10032 Timing: Fiscal Year 2002; Project Start 01-APR-2002; Project End 31-MAR-2007 Summary: (provided by the applicant): The three main chondroitin sulfate proteoglycans (CSPGs) of the arterial wall are versican and two small leucine rich proteoglycans (SLRPs), decorin & biglycan. We have performed the first study of atherogenesis in a CSPG knock-out, the decorin null mouse, which unexpectedly exhibited a substantial increase in lesions. The focus of this Project is to understand the effects of the decorin and biglycan CSPGs in atherogenesis on a molecular level, by
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broadly examining known functions and functional domains. Our central hypothesis is that the primary role of decorin in atherogenesis is not as a retentive molecule, but instead as a regulatory molecule that reduces the ability of locally synthesized biglycan and versican to retain lipoproteins. In contrast, we hypothesize that biglycan is primarily a retentive molecule, leading to pro-atherogenic effects. The proposed approaches follow the major theme of the SCOR, namely, the use of genetic manipulations of mice to investigate roles of specific arterial-wall molecules in atherogenesis. This Project involves extensive collaborations with Project 1, the Pathology Core, the Gene Expression Core, and the Clinical Core, and there is a shared theme with Project 8. Aim 1: Effects of decorin on atherogenic processes within the arterial wall in vivo. Four regulatory functions of decorin have been reported, each of which could be considered anti-atherogenic, particularly the inhibition of TGFbeta action. We will assess the effect of the decorin KO on arterial proteoglycan structure and lipoprotein binding, which are known to be altered by TGFbeta; and use real-time PCR and a broader gene chip survey to quantitate mRNAs, such as biglycan, that are affected by regulatory actions of decorin. Aim 2: Novel mouse models to investigate the role of decorin in atherogenesis. We will examine biglycan/decorin double KOs, to determine if overexpression of biglycan contributes to atherogenesis in decorin deficient mice. To determine the roles of the decorin domains for CS attachment and high-affinity TGFbeta binding, we propose to engineer mice lacking each of these domains, then quantitate development of atherosclerosis. Aim 3: A comprehensive search for decorin alleles that affect human vascular disease. We will perform a comprehensive search for common and rare human decorin polymorphisms. We will then screen human cohorts for the relationship of these decorin polymorphisms to cardiovascular disease. Overall, our proposed studies will establish the molecular roles of specific arterial-wall CSPGs and their, specific functional domains in atherogenesis in vivo in mice, with extensions to the human disease. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •
Project Title: STABILIZATION OF THE CUMULUS ECM AND OVULATION Principal Investigator & Institution: Sherman, Larry S.; Associate Professor; Cell Biol, Neurobiol/Anatomy; University of Cincinnati 2624 Clifton Ave Cincinnati, Oh 45221 Timing: Fiscal Year 2001; Project Start 01-AUG-1993; Project End 31-JAN-2003 Summary: Recently, the applicant has conducted studies to explore the function of the plasma glycoproteins of the inter-alpha-inhibitor family (inter-alpha-inhibitor; (IalphaI) and pre-alpha-inhibitor (PalphaI) in the processes of cumulus expansion and ovulation. Briefly, the LH-nitric oxide-mediated grating of a blood-follicle barrier allows influx of IalphaI and PalphaI from the plasma into the follicle and their subsequent binding to newly synthesized hyaluronic acid (HA) and stabilization of the cumulus extracellular matrix (cECM). Then, catalyzed by a factor produced by membrana glanulosa cells, the light chain (bikunin)-chondroitin sulfate moieties of IalphaI and PalphaI are released and hyaluronic acid becomes covalently bound to the heavy chain(s). This apparent transesterification reaction results in an increase in COC viscosity and elasticity and thus, the "superstabilization" of the cECM. Meanwhile some of the bikunin becomes incorporated into an, as yet unknown compartment of the COC. They have been keenly interested in the reproductive significance of these reactions and have reasoned that an understanding of these dramatic biochemical and physical transformation within the cECM may hold a key to the function of these molecules in reproductive functions of the COC including: (1) extrusion of the COC from the follicle; (2) integrity of the COC and its viability within the reproductive tract, and (3) fertilizability of the oocyte.
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Experiments in the present proposal are therefore designed to perturb biochemical and physical properties of COCs related to the synthesis of HA and the incorporation and reactions of IalphaI and PalphaI within the cECM. Experiments described in the following three specific aims are thus designed to analyze the following general hypothesis: Incorporation and covalent binding of IalphaI heavy chains into the cECM is required for function of the cumulus mass in ovulation, oocyte viability and fertilization. Effects of these perturbations will be carefully monitored and controlled by measurements of HA, IalphaI/PalphaI, heavy chain and bikunin levels within the CoC. In addition the elasticity and viscosity of the COC as well as qualities of the zona will be measured. These parameters will then be related to reproductive variables such as follicle rupture, extrusion of the COC from the follicle, integrity of the cumulus and viability and fertizability of the oocyte. The studies will establish fundamental conditions of cumulus expansion that may (1) reveal ovarian targets of diseases that affect female fertility, (2) enhance reproductive efficency in human or domestic animal IVF protocols or (3) provide a basis for targeted and reversible contraceptive strategies. (4) The studies may also elucidate aspects of IalphaI/PalphaI function relevant to functions of extracellular matrix in other tissues. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •
Project Title: STUDIES OF ADULT BRAIN NEUROPOIESIS Principal Investigator & Institution: Steindler, Dennis A.; Professor; Neuroscience; University of Florida Gainesville, Fl 32611 Timing: Fiscal Year 2003; Project Start 30-SEP-1999; Project End 30-JUN-2007 Summary: (provided by applicant): Homing, maintenance, and integration of stem cells in the central nervous system are rather new topics in emerging fields of neuropoiesis and regeneration neurobiology. The notion of stem cell plasticity has been advanced by different examples of so-called tissue specific stem cells being coaxed into other tissue phenotypes. This altering fate of tissue-specific stem cells, inducing transdifferentiation, has been reported in many different bioassays, using a variety of cell culture and in vivo conditions and manipulations. This proposal will compare homing, stem cell renewal, fate control and differentiation under neuralizing conditions in a persistently neurogenic (or "neuropoietic") region of the adult rodent brain - the subependymal zone (SEZ) and its rostral migratory stream (RMS) that is involved in continual repopulation of forebrain structures including the olfactory bulb. Three specific aims are proposed that will evaluate two candidate stem cell populations from brain (multipotent astrocytic stem cells, or "NSC" for neural stem cells) and blood ("HSC", hematopoietic stem cells) using in vivo and in vitro bridging bioassays. Specific Aim 1 will test the hypothesis that particular extracellular matrix molecules (tenascin-C and chondroitin sulfate proteoglycan), a candidate integrin receptor, cell surface molecules (CD 15 and CD9), and a chemokine and its receptor (SDF-1/CXCR4) are expressed by these cells and the SEZ/RMS to facilitate stem cell homing, maintenance and integration. Aim 2 will further test this, via studying the possible actions of these molecules in vivo following transplantation of NSC and HSC, using knockout animals and function blocking antibodies to these candidate homing/integration factors. Finally, Aim 3 will test the hypothesis that NSC and HSC can functionally integrate within forebrain neurogenic structures, using sensitive morphological and electrophysiological analyses of tissue explants - stem cell coplants. Before we can understand the potential of blood cells to become brain cells, a profound example of transdifferentiation that offers numerous alternative approaches to current cell replacement therapies, it is necessary to understand degrees of stemness of starting cell populations, and also elucidate factors
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involved in stem cell homing, maintenance, and integration to and within damaged CNS circuits. The studies proposed here also provide insights into long term culturing and integration of neuropoietic and hematopoietic cells, with an eye toward the development of therapeutics for a variety of brain and blood diseases. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •
Project Title: SULFOTRANSFERASE IN THE SYNTHESIS OF L-SELECTIN LIGANDS Principal Investigator & Institution: Rosen, Steven D.; Professor; Anatomy; University of California San Francisco 500 Parnassus Ave San Francisco, Ca 94122 Timing: Fiscal Year 2001; Project Start 01-JAN-1999; Project End 31-DEC-2002 Summary: L-selectin mediates the initial adhesion of lymphocytes to high endothelial venules (HEV) in lymph nodes during the process of lymphocyte recirculation. It also functions in leukocyte-leukocyte and leukocyte-endothelial interactions that occur during trafficking of leukocytes into inflammatory sites in both acute and chronic settings. L-selectin functions as a lectin-like receptor in recognizing a discrete set of HEV-ligands including GlyCAM-1, CD34, podocalyxin, Sgp200 and MAdCAM-1. These ligands are sulfated, fucosylated and sialylated, and all three of these modifications are required for optimal recognition by L-selectin. In addition, these glycoproteins are recognized by the monoclonal antibodies (MECA 79 and G72), which bind to sulfated substructures that are essential for their ligand activity. A detailed carbohydrate analysis of GlyCAM-1 has revealed that specific sulfation modifications of sialyl Lewis X are found: Gal-6-sulfation and N- acetylglucosamine-6-sulfation. This proposal is directed at the identification of the sulfotransferases, which catalyze these specific sulfation modifications of the HEV-associated ligands. One of the few cloned sulfotransferases that modifies carbohydrate chains is the chick chondroitin 6/keratan sulfate sulfotransferase (C6ST/KSST). This enzyme is capable of catalyzing the addition of sulfate to the 6-position of Gal in simple acceptor structures. We gave recently cloned 3 human cDNAs (GST 1, 2, and 3) which are highly homologous to the chicken C6ST/KSST. One of these (GST 3) is selectively expressed in the endothelial cells of HEV. The specific aims of the present proposal are: 1)To determine whether expressed proteins corresponding to the newly cloned GSTs (especially GST 3) catalyze the appropriate addition of sulfate moieties to model carbohydrate acceptors and to the carbohydrate chains of GlyCAM-1; 2) To identify the sulfated carbohydrate epitope recognized by MECA 79; and 3) To obtain cDNAs encoding HEC sulfotransferases by expression cloning techniques using the sulfation-dependent mAbs (G72 and MECA 79) and L-selectin. Understanding these enzymes has important biomedical implications, because the regulation of these enzymes provides a potential mechanism to control the expression of functional ligands for L-selectin, and thereby to control leukocyte trafficking into lymphoid organs and inflammatory sites. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen
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Project Title: SYNTHESIS OF GLYCOSAMINOGLYCAN OLIGOSACCHARIDES Principal Investigator & Institution: Linhardt, Robert J.; F. Wendel Miller Distinguished Professor; Chemistry; University of Iowa Iowa City, Ia 52242 Timing: Fiscal Year 2001; Project Start 15-DEC-2000; Project End 30-NOV-2004 Summary: (Principal Investigator's Abstract) Glycosaminoglycans (GAGs) are a family of structurally complex, highly sulfated, polydisperse, linear polysaccharides. Heparin, heparan sulfate, chondroitin sulfates, dermatan sulfate, and hyaluronic acid are all
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members of this family. Heparin, the most widely studied GAG, is a major activator of serine protease inhibitors and more recently heparin and other GAGs have been shown to be important in the regulation of cell growth and cell-cell interaction. Nearly 300 metric tons of heparin are produced worldwide each year from animal tissue and used as an anticoagulant. This activity results from heparin binding to antithrombin III making it a potent inhibitor of thrombin and other important serine proteases. The pentasaccharide sequence binding to antithrombin, has been chemically synthesized in greater than 60 synthetic steps and in less than 0.25 percent yield. Despite this challenging synthesis, this pentasaccharide is being used therapeutically throughout Europe. The chemical synthesis of heparin has not been attempted because of its large size and complex structure. There have been few reports of the synthesis of the oligosaccharide comprising the other GAGs. The synthesis of GAG oligosaccharides is proposed in which the GAG is first depolymerized into disaccharides using polysaccharide lyases. Five target structures have been chosen for synthesis: (1) a heparan sulfate tetrasaccharide with a variety of sulfation patterns; (2) a heparan sulfate octasaccharide; (3) the heparin tetrasaccharide and octasaccharide that bind basic fibroblast growth factor (FGF); (4) analogs of the FGF binding heparin tetrasaccharide containing modified functional groups will be synthesized using a novel sulfate imprinting method and used in structure activity relationship studies; (5) hybrid glycosaminoglycan oligosaccharides synthesized using lyase derived disaccharide building blocks from heparin, heparan sulfate, chondroitin sulfate, dermatan sulfate and hyaluronic acid. The interaction of these synthetic oligosaccharides to a number of GAG-binding proteins will be evaluated. Lyases will be applied to modified GAGs to prepare tetrasaccharides that will extend the chemistry developed in this proposal to larger oligosaccharide targets. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •
Project Title: THE FNA D REGION OF TENASCIN C AND NEURONAL GROWTH Principal Investigator & Institution: Meiners, Sally A.; Pharmacology; Univ of Med/Dent Nj-R W Johnson Med Sch Robert Wood Johnson Medical Sch Piscataway, Nj 08854 Timing: Fiscal Year 2001; Project Start 01-JUN-2001; Project End 31-MAR-2005 Summary: (From the Applicant's Abstract): The overall aim of our research is to understand how the growth of neurons is modulated by interaction with extracellular matrix molecules. This proposal centers upon understanding how the extracellular matrix molecule tenascin-C regulates neuronal growth. Tenascin-C is not a single molecule, but is instead a family of alternatively spliced variants containing different combinations of fibronectin type III domains. We have found that the region of tenascinC containing only the alternately spliced fibronectin type III domains, called fnA-D, when used by itself, dramatically increases neurite outgrowth in culture. In fact, this molecule is the most potent growth promoter we have identified in our tests in culture. The alternatively spliced region also provides directional cues to growing neurites, which we define as neurite guidance. Neurites demonstrate a strong preference for fbAD when they are given a choice at an interface. FnA-D even influences extension into normally repulsive chondroitin sulfate proteoglycans, the major inhibitory molecules in the glial scar. We have associated these features with different domains of the fnA-D molecule: promotion of neurite outgrowth with fnD (the seventh fibronectin type III domain), and neurite guidance with fnC (the sixth domain). More specifically we further localized the outgrowth activity to the 8 amino acids 29-36 within fnD which we call the "outgrowth promoting motif" (OPM). We have also determined that an antibody
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directed against the OPM can reduce neurite outgrowth by tenascin-C, thus demonstrating that this region is functional within the intact molecule. Our initial goal is thus to explore the hypothesis that neurite outgrowth and neurite guidance mediated by fnA-D are distinct processes, each of which can be manipulated independently to encourage directed neuronal regrowth. In addition, we will explore the hypothesis that these domains of tenascin-C may have properties as soluble chemoattractant molecules. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •
Project Title: TIMP ENGINEERING AND APPLICATION TO ARTHRITIS Principal Investigator & Institution: Brew, Keith; Professor; Biomedical Sciences; Florida Atlantic University Boca Raton, Fl 33431 Timing: Fiscal Year 2003; Project Start 01-SEP-1991; Project End 31-MAR-2008 Summary: (provided by applicant): The matrix metalloproteinases (MMPs) are zinc metalloproteinases that degrade components of the extracellular matrix. They play major roles in diseases including arthritis, cancer and atherosclerosis. The activities of MMPs are regulated by endogenous inhibitors, tissue inhibitors of metalloproteinases (TIMPs)-1, to -4. Our long-range goals are to understand how TIMPs inhibit MMPs and to use this information to engineer variant TIMPs that selectively inhibit individual or chosen groups of metalloproteinases. These targeted TIMPs will be tested for efficacy in alleviating the progression of diseases associated with increased degradation of the extracellular matrix. Our recent finding that TIMP-3 is a potent inhibitor of two aggrecanases (ADAMTS-4 and ADAMTS-5), key enzymes in the degradation of the cartilage proteoglycan, aggrecan, leads us to further investigate and test TIMP-3, and other TIMP variants, as inhibitors for preventing the progression of arthritis. To achieve these goals we will elucidate the structural basis of TIMP specificity for aggrecanases and MMPs and engineer TIMPs that are targeted for metalloproteinases involved in cartilage degradation. These inhibitors will be tested for effectiveness in ex vivo and in vivo models of rheumatoid arthritis (RA) and osteoarthritis (OA). The Specific Aims are: (1) to investigate the mechanism of inhibition of aggrecanases by TIMP-3 and generate specific inhibitors of these enzymes; (2) to produce TIMP variants that selectively inhibit collagenases (MMP-1 and -13), gelatinase A (MMP-2), or MT1-MMP; (3) identify and characterize low-molecular weight peptide inhibitors employing non-toxic variants of sarafotoxin, an analogue of the unique inhibitory region of TIMPs; (4) characterize the structural and physical basis of strong and specific metalloproteinase binding in TIMPs; (5) test recombinant TIMP-3 and other wild-type and variant TIMPs for their ability to prevent cartilage breakdown using the cartilage explant system; (6) test the efficacy of TIMP-3 and TIMP variants as potential blockers of cartilage degradation in the collageninduced arthritis model of RA, and in the STR/ort mouse OA model; and (7) identify metalloproteases that act in articular cartilage breakdown during the progression of OA in humans. These studies will produce mechanistic and structural information about the interactions of TIMPs and metalloproteinases and new insights into therapeutic approaches for arthritis. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen
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Project Title: TPA MEDIATED NEURODEGENERATION AND MICROGLIA ACTIVATION Principal Investigator & Institution: Tsirka, Styliani-Anna E.; Psychiatry and Behavioral Scis; State University New York Stony Brook Stony Brook, Ny 11794 Timing: Fiscal Year 2001; Project Start 01-FEB-1997; Project End 31-DEC-2002
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Summary: Neuronal cell death takes place both during normal development and in various pathological conditions such as epilepsy, Alzheimer's disease, and brain ischemia. We have found that tissue plasminogen activator (tPA), a serine protease that converts plasminogen to plasmin, mediates neuronal cell death in the hippocampus. In addition, tPA mediates activation of microglia, the "immune" cells of the brain. tPA has long been known to be expressed under basal conditions by neurons. After excitotoxic injury, however, we have found that the primary source of hippocampal tPA becomes newly activated microglia. We propose to: 1. Identify tPA/plasmin substrate(s) that mediate physiological function. tPA is expressed in the mammalian brain under physiological conditions and is secreted during neuronal remodeling. Preliminary data suggest that tPA/plasmin are involved in mossy fiber sprouting after stimulation of neuronal activity. Chondroitin sulfate proteoglycans represent promising candidates and will be analyzed further. In addition, chemokines will be evaluated as potential targets for tPA/plasmin action. 2. Dissect the neuronal cell death pathway mediated by tPA. Our preliminary evidence suggests that tPA mediates excitotoxic death in the hippocampus via apoptosis. We will confirm this observation and define the pathway of signaling, including potential role(s) played by microglia. 3. Determine whether tPA is required for neurodegeneration in a related setting. A mutant mouse that displays spontaneous neuronal degeneration will be outcrossed to homozygous tPA-/- mice. Their progeny will then be used to determine whether the absence of tPA confers protection to the neurons at risk in the mutant genotype. 4. Investigate the involvement of tPA in human neurodegeneration. The autoimmune disease multiple sclerosis (MS) is characterized in part by a marked increase in activated microglia, high levels of tPA activity that mirror disease progression, and neurodegeneration. We propose to use an MS animal model to evaluate the potential role of tPA in MS, in order to determine whether it is likely to be a requisite part of the neurodegenerative pathway, or is likely to be useful solely as a marker for disease progression. The aim will include validating the model by correlating changes in levels of tPA activity with the disease progression, and manipulating tPA activity levels to determine if the disease progression can be altered. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •
Project Title: TRABECULAR BONE-DERIVED CHONDROPROGENITOR CELLS Principal Investigator & Institution: Danielson, Keith G.; Professor; Orthopaedic Surgery; Thomas Jefferson University Office of Research Administration Philadelphia, Pa 191075587 Timing: Fiscal Year 2001; Project Start 01-APR-2001; Project End 31-MAR-2004 Summary: (Taken from the application): Wound healing and fracture repair in adult bone proceed via callus formation and an endochondral ossification sequence, where newly formed cartilage proliferates, matures, and undergoes hypertrophy, and is eventually replaced by the new bone that bridges the fracture gap. During this process, chondro- and osteo-progenitor cells are recruited to the damaged tissue site and are induced to differentiate in a s-atiotemporal specific manner to give rise to the regenerate endochondral. These progenitor cells are thought to be derived from local (not hematogenous) sources, i.e. they represent endogenous cell populations within the adult bony skeleton. While there is strong evidence that the bone marrow stroma and the periosteum both contain mesenchymal progenitor cells, our working hypothesis in this application is that multipotent progenitor cells, such as chondroprogenitor cells, are in fact also localized within the osteoid matrix of adult mature bone. This hypothesis is supported by our preliminary results that cells isolated from explants of fragments of
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adult human trabecular bone, traditionally denoted as "osteoblast-like cells", can be induced to differentiate into chondrocyte-like cells when maintained as an aggregate pellet culture, and secrete a sulfated proteoglycan-rich matrix containing collagen type I1. This induction of chondrogenesis is enhanced by factors such as transforming growth factor (TGF)-Bi or bone morphogenetic protein-2 (BMP-2), which have previously been shown to promote chondrogenesis in embryonic mesenchymal cells. We propose that these osteoblastic cells may represent a previously unrecognized population of multipotential mesenchymal progenitor cells. The Specific Aims are: 1 ) To identify and isolate chondroprogenitor cells from adult human trabecular bone; 2) To characterize the differentiation program of bone-derived chondroprogenitor cells; and 3) To determine the plasticity of the chondrogenic activity of bone-derived chondroprogenitor cells. Completion of these studies should clarify the characteristics and regulation of differentiation of a novel, chondroprogenitor cell population. This research will also determine if these adult trabecular bone-derived cells may serve as a progenitor cell source for cartilage engineering and repair. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •
Project Title: TYPE OSTEOARTHRITI
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Principal Investigator & Institution: Poole, Anthony R.; Director, Joint Diseases Laboratory; Mc Gill University James Admin. Bldg., Room 429 Montreal, Pq H3a 2T5 Timing: Fiscal Year 2001; Project Start 01-JUN-1996; Project End 31-MAY-2004 Summary: The applicant seeks to investigate molecular changes that occur in the extracellular matrix of cartilage in aging and in osteoarthritis (OA) that are associated with the degeneration of cartilage. Specifically, we seek to identify molecular damage to athe triple helix of type Ii collagen (ordinarily caused by collagenases) that is thought to occur in ageing and occurs in IA. Since type II collagen containing fibrils provide the tensile properties of cartilage and its molecular integrity, an understanding of how these events occur could lead to new therapeutic means of presenting these changes that lead to loss of joint function. We will examine aging human knee articular cartilages from autopsy and OA cartilages at arthroplasty, and those from the talus (ankle) (autopsy only). Cartilage degeneration is commonly observed in the knee and rarely in the ankle. New immunochemical methods, assays and immunolocalization methods developed in the applicant's laboratory will be used to detect and measure type II collagen a chain denaturation and cleavage at specific sites of the triple helix of human type II collagen in situ. This cleavage will be released to cleavage of isolated human type II collagen produced by the three collagenases, MMP-1, 8 and 13. Also, in situ type II collagen damage will be related to local mRNA expression and protein contents of these three human collagenases that may be present and cause this damage to type II collagen. The relationship of these proteinases to chondrocyte hypertrophy (marked by production of type X collagen) will be examined by in situ hybridization and immunochemical methods. Comparisons will be made of early focal aging lesions with adjacent cartilages and of defined sites in aging and OA cartilages. These studies will provide evidence for whether aging and OA are two distinct degenerative process or whether they are part of a continuing degenerative process, whereby OA represents a clinical progression of an aging process. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen
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Project Title: VASCULAR EFFECTS OF HEPARAN SULFATE PROTEOGLYCANS Principal Investigator & Institution: Goldberg, Ira J.; Professor of Medicine; Columbia University Health Sciences New York, Ny 10032 Timing: Fiscal Year 2002; Project Start 01-APR-2002; Project End 31-MAR-2007 Summary: (provided by the applicant): Proteoglycans are major structural proteins that contribute to the integrity of the artery and affect the metabolism of atherogenic lipoproteins. Although interaction of lipoproteins with dermatan sulfate/chondroitin sulfate proteoglycans is widely believed to lead to lipoprotein retention, heparan sulfate proteoglycans (HSPGs) may be anti-atherogenic because they help form a barrier that prevents lipoprotein penetration into the artery wall. This Project contains 3 Aims to study the roles of HSPGs in regulation of atherogenic lipoproteins and arterial wall biology. In Aim 1 we propose experiments to modulate subendothelial HSPG(s) in monolayer cultures of endothelial cells and assess how this alters parameters of atherosclerosis including lipoprotein retention, endothelial permeability and migration of monocytes. The goal of Aim 2 is to assess atherosclerosis and lipoprotein metabolism in mice with a defect in perlecan production. Aim 3 will correlate expression of perlecan and its degradative enzyme heparanase in normal and diseased arteries from mice and humans, and will study the regulation of endothelial heparanase in vivo. Endothelial heparanase is expressed as a response to inflammatory stimuli in cultured cells, and we will assess whether this enzyme is likely to alter arterial biology during atherosclerosis. The theme of this Project is consistent with the overall goals of this SCOR to study atherogenic processes in genetically modulated mice. It also encompasses several subthemes that interrelate with other projects of this SCOR. These include the biochemistry of lipoprotein retention by arterial molecules (Projects 1 & 7), studies of arterial wall enzymes (Project 1) and arterial effects of atherogenic and anti-atherogenic lipoproteins (Project 6 & 7). Moreover, the information obtained from the in vitro and animals studies will be used to relate HSPGs to human atherosclerosis by studying perlecan and heparanase gene expression in human arteries. 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 “chondroitin” (or synonyms) into the search box. This search gives you access to full-text articles. The following is a sample of items found for chondroitin in the PubMed Central database:
3 4
Adapted from the National Library of Medicine: http://www.pubmedcentral.nih.gov/about/intro.html.
With PubMed Central, NCBI is taking the lead in preservation and maintenance of open access to electronic literature, just as NLM has done for decades with printed biomedical literature. PubMed Central aims to become a world-class library of the digital age. 5 The value of PubMed Central, in addition to its role as an archive, lies in the availability of data from diverse sources stored in a common format in a single repository. Many journals already have online publishing operations, and there is a growing tendency to publish material online only, to the exclusion of print.
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Biological and Biochemical Characteristics of Cytoadhesion of Plasmodium falciparum-Infected Erythrocytes to Chondroitin-4-Sulfate. by Pouvelle B, Fusai T, Lepolard C, Gysin J.; 1998 Oct; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=108613
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Chondroitin Sulfate Proteoglycan Expression and Binding of Plasmodium falciparum-Infected Erythrocytes in the Human Placenta during Pregnancy. by AgborEnoh ST, Achur RN, Valiyaveettil M, Leke R, Taylor DW, Gowda DC.; 2003 May; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=153269
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Cytoadherence of Plasmodium falciparum to intercellular adhesion molecule 1 and chondroitin-4-sulfate expressed by the syncytiotrophoblast in the human placenta. by Maubert B, Guilbert LJ, Deloron P.; 1997 Apr; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&rendertype=abstr act&artid=175125
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Development of Antibodies against Chondroitin Sulfate A-Adherent Plasmodium falciparum in Pregnant Women. by Maubert B, Fievet N, Tami G, Cot M, Boudin C, Deloron P.; 1999 Oct; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=96893
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Ex Vivo Desequestration of Plasmodium falciparum-Infected Erythrocytes from Human Placenta by Chondroitin Sulfate A. by Gysin J, Pouvelle B, Fievet N, Scherf A, Lepolard C.; 1999 Dec; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=97072
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Glucosamine and chondroitin sulfate supplementation to treat symptomatic disc degeneration: Biochemical rationale and case report. by van Blitterswijk WJ, van de Nes JC, Wuisman PI.; 2003; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=165439
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Gravidity-Dependent Production of Antibodies That Inhibit Binding of Plasmodium falciparum-Infected Erythrocytes to Placental Chondroitin Sulfate Proteoglycan during Pregnancy. by O'Neil-Dunne I, Achur RN, Agbor-Enoh ST, Valiyaveettil M, Naik RS, Ockenhouse CF, Zhou A, Megnekou R, Leke R, Taylor DW, Gowda DC.; 2001 Dec; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=98838
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Human single-chain Fv immunoconjugates targeted to a melanoma-associated chondroitin sulfate proteoglycan mediate specific lysis of human melanoma cells by natural killer cells and complement. by Wang B, Chen YB, Ayalon O, Bender J, Garen A.; 1999 Feb 16; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=15540
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Identification and characterization of a Bacteroides gene, csuF, which encodes an outer membrane protein that is essential for growth on chondroitin sulfate. by Cheng Q, Yu MC, Reeves AR, Salyers AA.; 1995 Jul; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&rendertype=abstr act&artid=177088
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Identification of Glycosaminoglycan Binding Domains in Plasmodium falciparum Erythrocyte Membrane Protein 1 of a Chondroitin Sulfate A-Adherent Parasite. by Reeder JC, Hodder AN, Beeson JG, Brown GV.; 2000 Jul; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=101668
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Inhibition of Binding of Malaria-Infected Erythrocytes by a Tetradecasaccharide Fraction from Chondroitin Sulfate A. by Beeson JG, Chai W, Rogerson SJ, Lawson AM, Brown GV.; 1998 Jul; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=108358
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Isolation and Expression in Escherichia coli of cslA and cslB, Genes Coding for the Chondroitin Sulfate-Degrading Enzymes Chondroitinase AC and Chondroitinase B, Respectively, from Flavobacterium heparinum. by Tkalec AL, Fink D, Blain F, ZhangSun G, Laliberte M, Bennett DC, Gu K, Zimmermann JJ, Su H.; 2000 Jan; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=91781
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Molecular basis for the dichotomy in Plasmodium falciparum adhesion to CD36 and chondroitin sulfate A. by Gamain B, Gratepanche S, Miller LH, Baruch DI.; 2002 Jul 23; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=126617
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Molecular Cloning of a Human Melanoma-Associated Chondroitin Sulfate Proteoglycan. by Pluschke G, Vanek M, Evans A, Dittmar T, Schmid P, Itin P, Filardo EJ, Reisfeld RA.; 1996 Sep 3; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&rendertype=abstr act&artid=38494
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Phosphacan, a Chondroitin Sulfate Proteoglycan of Brain that Interacts with Neurons and Neural Cell-Adhesion Molecules, is an Extracellular Variant of a Receptor-Type Protein Tyrosine Phosphatase. by Maurel P, Rauch U, Flad M, Margolis RK, Margolis RU.; 1994 Mar 29; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&rendertype=abstr act&artid=43399
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Plasmodium falciparum domain mediating adhesion to chondroitin sulfate A: A receptor for human placental infection. by Buffet PA, Gamain B, Scheidig C, Baruch D, Smith JD, Hernandez-Rivas R, Pouvelle B, Oishi S, Fujii N, Fusai T, Parzy D, Miller LH, Gysin J, Scherf A.; 1999 Oct 26; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=23079
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The adhesion of Plasmodium falciparum-infected erythrocytes to chondroitin sulfate A is mediated by P. falciparum erythrocyte membrane protein 1. by Reeder JC, Cowman AF, Davern KM, Beeson JG, Thompson JK, Rogerson SJ, Brown GV.; 1999 Apr 27; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=21841
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The C-type lectin domains of lecticans, a family of aggregating chondroitin sulfate proteoglycans, bind tenascin-R by protein -- protein interactions independent of carbohydrate moiety. by Aspberg A, Miura R, Bourdoulous S, Shimonaka M, Heinegard D, Schachner M, Ruoslahti E, Yamaguchi Y.; 1997 Sep 16; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=23322
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The Microfibrillar Proteins MAGP-1 and Fibrillin-1 Form a Ternary Complex with the Chondroitin Sulfate Proteoglycan Decorin. by Trask BC, Trask TM, Broekelmann T, Mecham RP.; 2000 May 1; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=14862
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Use of suppressor analysis to find genes involved in the colonization deficiency of a Bacteroides thetaiotaomicron mutant unable to grow on the host-derived mucopolysaccharides chondroitin sulfate and heparin. by Cheng Q, Salyers AA.; 1995 Feb; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&rendertype=abstr act&artid=167334
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Vaccinia Virus Envelope D8L Protein Binds to Cell Surface Chondroitin Sulfate and Mediates the Adsorption of Intracellular Mature Virions to Cells. by Hsiao JC, Chung CS, Chang W.; 1999 Oct; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=112896
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 chondroitin, simply go to the PubMed Web site at http://www.ncbi.nlm.nih.gov/pubmed. Type “chondroitin” (or synonyms) into the search box, and click “Go.” The following is the type of output you can expect from PubMed for chondroitin (hyperlinks lead to article summaries): •
2B1 antigen characteristically expressed on extracellular matrices of human malignant tumors is a large chondroitin sulfate proteoglycan, PG-M/versican. Author(s): Isogai Z, Shinomura T, Yamakawa N, Takeuchi J, Tsuji T, Heinegard D, Kimata K. Source: Cancer Research. 1996 September 1; 56(17): 3902-8. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=8752156&dopt=Abstract
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A biochemical and immuno-electron microscopical analysis of chondroitin sulphaterich proteoglycans in human alveolar bone. Author(s): Smith AJ, Singhrao SK, Newman GR, Waddington RJ, Embery G. Source: The Histochemical Journal. 1997 January; 29(1): 1-9. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=9088940&dopt=Abstract
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A chondroitin sulfate proteoglycan on human neutrophils specifically binds platelet factor 4 and is involved in cell activation. Author(s): Petersen F, Bock L, Flad HD, Brandt E. Source: Journal of Immunology (Baltimore, Md. : 1950). 1998 October 15; 161(8): 4347-55. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=9780212&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 chondroitin/dermatan sulfate form of CD44 is a receptor for collagen XIV (undulin). Author(s): Ehnis T, Dieterich W, Bauer M, Lampe B, Schuppan D. Source: Experimental Cell Research. 1996 December 15; 229(2): 388-97. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=8986622&dopt=Abstract
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A deficit of chondroitin sulfate proteoglycans on the bladder uroepithelium in interstitial cystitis. Author(s): Hurst RE, Roy JB, Min KW, Veltri RW, Marley G, Patton K, Shackelford DL, Stein P, Parsons CL. Source: Urology. 1996 November; 48(5): 817-21. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=8911536&dopt=Abstract
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A fingerprinting method for chondroitin/dermatan sulfate and hyaluronan oligosaccharides. Author(s): Lauder RM, Huckerby TN, Nieduszynski IA. Source: Glycobiology. 2000 April; 10(4): 393-401. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10764827&dopt=Abstract
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A fucosylated chondroitin sulfate from echinoderm modulates in vitro fibroblast growth factor 2-dependent angiogenesis. Author(s): Tapon-Bretaudiere J, Chabut D, Zierer M, Matou S, Helley D, Bros A, Mourao PA, Fischer AM. Source: Molecular Cancer Research : Mcr. 2002 December; 1(2): 96-102. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12496356&dopt=Abstract
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A heparin-binding growth factor, midkine, binds to a chondroitin sulfate proteoglycan, PG-M/versican. Author(s): Zou K, Muramatsu H, Ikematsu S, Sakuma S, Salama RH, Shinomura T, Kimata K, Muramatsu T. Source: European Journal of Biochemistry / Febs. 2000 July; 267(13): 4046-53. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10866805&dopt=Abstract
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A human schwannoma cell line supports the in vitro adhesion of Plasmodium falciparum infected erythrocytes to chondroitin-4-sulfate. Author(s): Andrews KT, Viebig NK, Wissing F, Klatt N, Oster N, Wickert H, Knolle P, Lanzer M. Source: Parasitology Research. 2003 February; 89(3): 188-93. Epub 2002 October 08. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12541060&dopt=Abstract
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A hyaluronan binding link protein gene family whose members are physically linked adjacent to chondroitin sulfate proteoglycan core protein genes: the missing links. Author(s): Spicer AP, Joo A, Bowling RA Jr. Source: The Journal of Biological Chemistry. 2003 June 6; 278(23): 21083-91. Epub 2003 March 27. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12663660&dopt=Abstract
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A Japanese case of steroid responsive myopathy with deficient chondroitin sulphate. Author(s): Yabe I, Kikuchi S, Higashi T, Tashiro K, Maruo Y. Source: Journal of Neurology, Neurosurgery, and Psychiatry. 2002 July; 73(1): 89-90. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12082062&dopt=Abstract
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A metaanalysis of chondroitin sulfate in the treatment of osteoarthritis. Author(s): Leeb BF, Schweitzer H, Montag K, Smolen JS. Source: The Journal of Rheumatology. 2000 January; 27(1): 205-11. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10648040&dopt=Abstract
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A monoclonal antibody which recognizes a glycosaminoglycan epitope in both dermatan sulfate and chondroitin sulfate proteoglycans of human skin. Author(s): Sorrell JM, Carrino DA, Baber MA, Asselineau D, Caplan AI. Source: The Histochemical Journal. 1999 August; 31(8): 549-58. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10507462&dopt=Abstract
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A novel repeat in the melanoma-associated chondroitin sulfate proteoglycan defines a new protein family. Author(s): Staub E, Hinzmann B, Rosenthal A. Source: Febs Letters. 2002 September 11; 527(1-3): 114-8. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12220645&dopt=Abstract
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A randomized double-blind clinical trial of the effect of chondroitin sulfate and glucosamine hydrochloride on temporomandibular joint disorders: a pilot study. Author(s): Nguyen P, Mohamed SE, Gardiner D, Salinas T. Source: Cranio. 2001 April; 19(2): 130-9. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11842864&dopt=Abstract
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A randomized, double blind, placebo controlled trial of a topical cream containing glucosamine sulfate, chondroitin sulfate, and camphor for osteoarthritis of the knee. Author(s): Cohen M, Wolfe R, Mai T, Lewis D. Source: The Journal of Rheumatology. 2003 March; 30(3): 523-8. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12610812&dopt=Abstract
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A role of chondroitin sulfate glycosaminoglycan binding site in alpha4beta1 integrinmediated melanoma cell adhesion. Author(s): Iida J, Meijne AM, Oegema TR Jr, Yednock TA, Kovach NL, Furcht LT, McCarthy JB. Source: The Journal of Biological Chemistry. 1998 March 6; 273(10): 5955-62. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=9488735&dopt=Abstract
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A sensitive assay for the measurement of serum chondroitin sulfate 3B3(-) epitope levels in human rheumatic diseases. Author(s): Chan SS, Kent GN, Will RK. Source: Clin Exp Rheumatol. 2001 September-October; 19(5): 533-40. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11579712&dopt=Abstract
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A unique nonreducing terminal modification of chondroitin sulfate by Nacetylgalactosamine 4-sulfate 6-o-sulfotransferase. Author(s): Ohtake S, Kimata K, Habuchi O. Source: The Journal of Biological Chemistry. 2003 October 3; 278(40): 38443-52. Epub 2003 July 21. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12874280&dopt=Abstract
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Abnormal occurrence of a large chondroitin sulfate proteoglycan, PG-M/versican in osteoarthritic cartilage. Author(s): Nishida Y, Shinomura T, Iwata H, Miura T, Kimata K. Source: Osteoarthritis and Cartilage / Oars, Osteoarthritis Research Society. 1994 March; 2(1): 43-9. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11548223&dopt=Abstract
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Adaptation of FACE methodology for microanalysis of total hyaluronan and chondroitin sulfate composition from cartilage. Author(s): Calabro A, Hascall VC, Midura RJ. Source: Glycobiology. 2000 March; 10(3): 283-93. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10704527&dopt=Abstract
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Adherence of Plasmodium falciparum to chondroitin sulfate A in the human placenta. Author(s): Fried M, Duffy PE. Source: Science. 1996 June 7; 272(5267): 1502-4. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=8633247&dopt=Abstract
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Adherence of Plasmodium falciparum-infected erythrocytes to chondroitin 4-sulfate. Author(s): Gowda DC, Ockenhouse CF. Source: Bioscience Reports. 1999 August; 19(4): 261-71. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10589991&dopt=Abstract
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Adhesion of malaria-infected red blood cells to chondroitin sulfate A under flow conditions. Author(s): Cooke BM, Rogerson SJ, Brown GV, Coppel RL. Source: Blood. 1996 November 15; 88(10): 4040-4. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=8916971&dopt=Abstract
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Age-related changes in the sulphation of the chondroitin sulphate linkage region from human articular cartilage aggrecan. Author(s): Lauder RM, Huckerby TN, Brown GM, Bayliss MT, Nieduszynski IA. Source: The Biochemical Journal. 2001 September 1; 358(Pt 2): 523-8. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11513754&dopt=Abstract
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Aggregation of LDL with chondroitin-4-sulfate makes LDL oxidizable in the presence of water-soluble antioxidants. Author(s): Abuja PM. Source: Febs Letters. 2002 February 13; 512(1-3): 245-8. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11852089&dopt=Abstract
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alpha-N-acetylgalactosamine-capping of chondroitin sulfate core region oligosaccharides primed on xylosides. Author(s): Miura Y, Freeze HH. Source: Glycobiology. 1998 August; 8(8): 813-9. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=9639542&dopt=Abstract
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Altered fine structures of corneal and skeletal keratan sulfate and chondroitin/dermatan sulfate in macular corneal dystrophy. Author(s): Plaas AH, West LA, Thonar EJ, Karcioglu ZA, Smith CJ, Klintworth GK, Hascall VC. Source: The Journal of Biological Chemistry. 2001 October 26; 276(43): 39788-96. Epub 2001 August 20. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11514545&dopt=Abstract
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Amyloid-beta interactions with chondroitin sulfate-derived monosaccharides and disaccharides. implications for drug development. Author(s): Fraser PE, Darabie AA, McLaurin JA. Source: The Journal of Biological Chemistry. 2001 March 2; 276(9): 6412-9. Epub 2000 December 05. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11106653&dopt=Abstract
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Analysis of chondroitin sulfate in lumbar intervertebral discs at two different stages of degeneration as assessed by discogram. Author(s): Hutton WC, Elmer WA, Boden SD, Horton WC, Carr K. Source: Journal of Spinal Disorders. 1997 February; 10(1): 47-54. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=9041496&dopt=Abstract
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Annexin 6 is a putative cell surface receptor for chondroitin sulfate chains. Author(s): Takagi H, Asano Y, Yamakawa N, Matsumoto I, Kimata K. Source: Journal of Cell Science. 2002 August 15; 115(Pt 16): 3309-18. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12140262&dopt=Abstract
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Antibodies to chondroitin sulfate C: a new detection assay and correlations with neurological diseases. Author(s): Briani C, Berger JS, Latov N. Source: Journal of Neuroimmunology. 1998 April 15; 84(2): 117-21. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=9628452&dopt=Abstract
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Antibodies to chondroitin sulfates A, B, and C: clinico-pathological correlates in neurological diseases. Author(s): Briani C, Santoro M, Latov N. Source: Journal of Neuroimmunology. 2000 August 1; 108(1-2): 216-20. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10900356&dopt=Abstract
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Anti-inflammatory activity of chondroitin sulfate. Author(s): Ronca F, Palmieri L, Panicucci P, Ronca G. Source: Osteoarthritis and Cartilage / Oars, Osteoarthritis Research Society. 1998 May; 6 Suppl A: 14-21. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=9743814&dopt=Abstract
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Anti-tumor activities of chondroitinase AC and chondroitinase B: inhibition of angiogenesis, proliferation and invasion. Author(s): Denholm EM, Lin YQ, Silver PJ. Source: European Journal of Pharmacology. 2001 March 30; 416(3): 213-21. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11290371&dopt=Abstract
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ApoE of the HepG2 cell surface includes a major pool associated with chondroitin sulfate proteoglycans. Author(s): Burgess JW, Liang P, Vaidyanath C, Marcel YL. Source: Biochemistry. 1999 January 12; 38(2): 524-31. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=9888791&dopt=Abstract
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Appican, the proteoglycan form of the amyloid precursor protein, contains chondroitin sulfate E in the repeating disaccharide region and 4-O-sulfated galactose in the linkage region. Author(s): Tsuchida K, Shioi J, Yamada S, Boghosian G, Wu A, Cai H, Sugahara K, Robakis NK. Source: The Journal of Biological Chemistry. 2001 October 5; 276(40): 37155-60. Epub 2001 July 30. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11479316&dopt=Abstract
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Are glucosamine and chondroitin effective in treating osteoarthritis? Author(s): Denham AC, Newton WP. Source: The Journal of Family Practice. 2000 June; 49(6): 571-2. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10923559&dopt=Abstract
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Arterial wall chondroitin sulfate proteoglycans: diverse molecules with distinct roles in lipoprotein retention and atherogenesis. Author(s): Williams KJ. Source: Current Opinion in Lipidology. 2001 October; 12(5): 477-87. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11561166&dopt=Abstract
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Asthma exacerbation associated with glucosamine-chondroitin supplement. Author(s): Tallia AF, Cardone DA. Source: The Journal of the American Board of Family Practice / American Board of Family Practice. 2002 November-December; 15(6): 481-4. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12463294&dopt=Abstract
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Basement membrane zone type XV collagen is a disulfide-bonded chondroitin sulfate proteoglycan in human tissues and cultured cells. Author(s): Li D, Clark CC, Myers JC. Source: The Journal of Biological Chemistry. 2000 July 21; 275(29): 22339-47. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10791950&dopt=Abstract
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Benign hyperplasia of the human prostate is associated with tissue enrichment in chondroitin sulphate of wide size distribution. Author(s): Goulas A, Hatzichristou DG, Karakiulakis G, Mirtsou-Fidani V, Kalinderis A, Papakonstantinou E. Source: The Prostate. 2000 July 1; 44(2): 104-10. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10881019&dopt=Abstract
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Benzoporphyrin derivative decreases the binding of low density lipoprotein to the glycosaminoglycan chondroitin-6-sulfate in vitro. Author(s): Allison BA, Hamilton J. Source: Atherosclerosis. 1996 September 6; 125(2): 153-60. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=8842347&dopt=Abstract
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Binding of a large chondroitin sulfate/dermatan sulfate proteoglycan, versican, to Lselectin, P-selectin, and CD44. Author(s): Kawashima H, Hirose M, Hirose J, Nagakubo D, Plaas AH, Miyasaka M. Source: The Journal of Biological Chemistry. 2000 November 10; 275(45): 35448-56. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10950950&dopt=Abstract
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Binding of interleukin-8 to heparan sulfate and chondroitin sulfate in lung tissue. Author(s): Frevert CW, Kinsella MG, Vathanaprida C, Goodman RB, Baskin DG, Proudfoot A, Wells TN, Wight TN, Martin TR. Source: American Journal of Respiratory Cell and Molecular Biology. 2003 April; 28(4): 464-72. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12654635&dopt=Abstract
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Biochemical properties of a keratan sulphate/chondroitin sulphate proteoglycan expressed in primate pluripotent stem cells. Author(s): Cooper S, Bennett W, Andrade J, Reubinoff BE, Thomson J, Pera MF. Source: Journal of Anatomy. 2002 March; 200(Pt 3): 259-65. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12033730&dopt=Abstract
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Biosynthesis of chondroitin/dermatan sulfate. Author(s): Silbert JE, Sugumaran G. Source: Iubmb Life. 2002 October; 54(4): 177-86. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12512856&dopt=Abstract
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Biosynthesis of chondroitinase and hyaluronidase by different strains of Paracoccidioides brasiliensis. Author(s): de Assis CM, Gandra RF, Gambale W, Shimizu MT, Paula CR. Source: Journal of Medical Microbiology. 2003 June; 52(Pt 6): 479-81. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12748266&dopt=Abstract
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CD44, a cell surface chondroitin sulfate proteoglycan, mediates binding of interferongamma and some of its biological effects on human vascular smooth muscle cells. Author(s): Hurt-Camejo E, Rosengren B, Sartipy P, Elfsberg K, Camejo G, Svensson L. Source: The Journal of Biological Chemistry. 1999 July 2; 274(27): 18957-64. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10383394&dopt=Abstract
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CD44/chondroitin sulfate proteoglycan and alpha 2 beta 1 integrin mediate human melanoma cell migration on type IV collagen and invasion of basement membranes. Author(s): Knutson JR, Iida J, Fields GB, McCarthy JB. Source: Molecular Biology of the Cell. 1996 March; 7(3): 383-96. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=8868467&dopt=Abstract
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Cell surface chondroitin sulfate proteoglycans in tumor cell adhesion, motility and invasion. Author(s): Iida J, Meijne AM, Knutson JR, Furcht LT, McCarthy JB. Source: Seminars in Cancer Biology. 1996 June; 7(3): 155-62. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=8773301&dopt=Abstract
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Cell surface-associated chondroitin sulfate proteoglycans bind contact phase factor Hkininogen. Author(s): Renne T, Muller-Esterl W. Source: Febs Letters. 2001 June 29; 500(1-2): 36-40. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11434922&dopt=Abstract
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Changes in serum chondroitin sulphate epitopes 3-B-3 and 7-D-4 in early rheumatoid arthritis. Author(s): Middleton J, White S, Parry E, Jackson C, Dixey J, Ashton B. Source: Rheumatology (Oxford, England). 1999 September; 38(9): 837-40. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10515644&dopt=Abstract
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Characterisation of the chondroitin sulphate of Saimiri brain microvascular endothelial cells involved in Plasmodium falciparum cytoadhesion. Author(s): Fusai T, Parzy D, Spillmann D, Eustacchio F, Pouvelle B, Lepolard C, Scherf A, Gysin J. Source: Molecular and Biochemical Parasitology. 2000 April 30; 108(1): 25-37. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10802316&dopt=Abstract
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Characterization of appican, the chondroitin sulfate proteoglycan form of the Alzheimer amyloid precursor protein. Author(s): Pangalos MN, Shioi J, Efthimiopoulos S, Wu A, Robakis NK. Source: Neurodegeneration : a Journal for Neurodegenerative Disorders, Neuroprotection, and Neuroregeneration. 1996 December; 5(4): 445-51. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=9117561&dopt=Abstract
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Characterization of cell surface-expressed proteochondroitin sulfate of pre-B Nalm-6 cells and its possible role in laminin adhesion. Author(s): Blase L, Merling A, Engelmann S, Moller P, Schwartz-Albiez R. Source: Leukemia : Official Journal of the Leukemia Society of America, Leukemia Research Fund, U.K. 1996 June; 10(6): 1000-11. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=8667635&dopt=Abstract
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Characterization of proteoglycans of human placenta and identification of unique chondroitin sulfate proteoglycans of the intervillous spaces that mediate the adherence of Plasmodium falciparum-infected erythrocytes to the placenta. Author(s): Achur RN, Valiyaveettil M, Alkhalil A, Ockenhouse CF, Gowda DC. Source: The Journal of Biological Chemistry. 2000 December 22; 275(51): 40344-56. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11005814&dopt=Abstract
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Chemical and immunological assay of the nonreducing terminal residues of chondroitin sulfate from human aggrecan. Author(s): Plaas AH, Wong-Palms S, Roughley PJ, Midura RJ, Hascall VC. Source: The Journal of Biological Chemistry. 1997 August 15; 272(33): 20603-10. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=9252375&dopt=Abstract
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Chitosan-chondroitin sulfate and chitosan-hyaluronate polyelectrolyte complexes: biological properties. Author(s): Denuziere A, Ferrier D, Damour O, Domard A. Source: Biomaterials. 1998 July; 19(14): 1275-85. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=9720891&dopt=Abstract
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Chondroitin 4-sulphate exhibits inhibitory effect during Cu2+-mediated LDL oxidation. Author(s): Albertini R, Ramos P, Giessauf A, Passi A, De Luca G, Esterbauer H. Source: Febs Letters. 1997 February 17; 403(2): 154-8. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=9042957&dopt=Abstract
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Chondroitin and keratan sulphate epitopes, glycosaminoglycans, and hyaluronan in progressive versus non-progressive osteoarthritis. Author(s): Fawthrop F, Yaqub R, Belcher C, Bayliss M, Ledingham J, Doherty M. Source: Annals of the Rheumatic Diseases. 1997 February; 56(2): 119-22. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=9068285&dopt=Abstract
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Chondroitin sulfate A released from platelets blocks RANTES presentation on cell surfaces and RANTES-dependent firm adhesion of leukocytes. Author(s): Mack M, Pfirstinger J, Weber C, Weber KS, Nelson PJ, Rupp T, Maletz K, Bruhl H, Schlondorff D. Source: European Journal of Immunology. 2002 April; 32(4): 1012-20. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11920567&dopt=Abstract
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Chondroitin sulfate and cytoplasmic domain-dependent membrane targeting of the NG2 proteoglycan promotes retraction fiber formation and cell polarization. Author(s): Stallcup WB, Dahlin-Huppe K. Source: Journal of Cell Science. 2001 June; 114(Pt 12): 2315-25. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11493670&dopt=Abstract
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Chondroitin sulfate and joint disease. Author(s): Hardingham T. Source: Osteoarthritis and Cartilage / Oars, Osteoarthritis Research Society. 1998 May; 6 Suppl A: 3-5. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=9743812&dopt=Abstract
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Chondroitin sulfate and other sulfate containing chondroprotective agents may exhibit their effects by overcoming a deficiency of sulfur amino acids. Author(s): Cordoba F, Nimni ME. Source: Osteoarthritis and Cartilage / Oars, Osteoarthritis Research Society. 2003 March; 11(3): 228-30. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12623294&dopt=Abstract
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Chondroitin sulfate in erosive osteoarthritis of the hands. Author(s): Rovetta G, Monteforte P, Molfetta G, Balestra V. Source: Int J Tissue React. 2002; 24(1): 29-32. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12013151&dopt=Abstract
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Chondroitin sulfate in osteoarthritis of the knee: a prospective, double blind, placebo controlled multicenter clinical study. Author(s): Mazieres B, Combe B, Phan Van A, Tondut J, Grynfeltt M. Source: The Journal of Rheumatology. 2001 January; 28(1): 173-81. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11196521&dopt=Abstract
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Chondroitin sulfate is involved in lysosomal transport of lysozyme in U937 cells. Author(s): Lemansky P, Hasilik A. Source: Journal of Cell Science. 2001 January; 114(Pt 2): 345-52. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11148136&dopt=Abstract
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Chondroitin sulfate isomers in synovial fluid of healthy and diseased human temporomandibular joints. Author(s): Okazaki J, Kakudo K, Kamada A, Utoh E, Gonda Y, Shirasu R, Sakaki T. Source: European Journal of Oral Sciences. 1997 October; 105(5 Pt 1): 440-3. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=9395105&dopt=Abstract
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Chondroitin sulfate of thrombomodulin is an adhesion receptor for Plasmodium falciparum-infected erythrocytes. Author(s): Gysin J, Pouvelle B, Le Tonqueze M, Edelman L, Boffa MC. Source: Molecular and Biochemical Parasitology. 1997 September; 88(1-2): 267-71. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=9274889&dopt=Abstract
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Chondroitin sulfate proteoglycan at the basal lamina beneath high endothelial cells in human palatine tonsils: a light and electron microscopic study using the cationic colloidal iron method. Author(s): Sunami-Kataoka Y, Akagi H, Nishizaki K, Taguchi T, Murakami T, Ohtsuka A. Source: Arch Histol Cytol. 2001 December; 64(5): 535-43. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11838713&dopt=Abstract
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Chondroitin sulfate proteoglycan core proteins in the interphotoreceptor matrix: a comparative study using biochemical and immunohistochemical analysis. Author(s): Hollyfield JG, Rayborn ME, Midura RJ, Shadrach KG, Acharya S. Source: Experimental Eye Research. 1999 September; 69(3): 311-22. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10471339&dopt=Abstract
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Chondroitin sulfate proteoglycan expression and binding of Plasmodium falciparuminfected erythrocytes in the human placenta during pregnancy. Author(s): Agbor-Enoh ST, Achur RN, Valiyaveettil M, Leke R, Taylor DW, Gowda DC. Source: Infection and Immunity. 2003 May; 71(5): 2455-61. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12704116&dopt=Abstract
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Chondroitin sulfate proteoglycans as mediators of axon growth and pathfinding. Author(s): Margolis RU, Margolis RK. Source: Cell and Tissue Research. 1997 November; 290(2): 343-8. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=9321696&dopt=Abstract
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Chondroitin sulfate synthase-2. Molecular cloning and characterization of a novel human glycosyltransferase homologous to chondroitin sulfate glucuronyltransferase, which has dual enzymatic activities. Author(s): Yada T, Gotoh M, Sato T, Shionyu M, Go M, Kaseyama H, Iwasaki H, Kikuchi N, Kwon YD, Togayachi A, Kudo T, Watanabe H, Narimatsu H, Kimata K. Source: The Journal of Biological Chemistry. 2003 August 8; 278(32): 30235-47. Epub 2003 May 20. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12761225&dopt=Abstract
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Chondroitin sulfate: S/DMOAD (structure/disease modifying anti-osteoarthritis drug) in the treatment of finger joint OA. Author(s): Verbruggen G, Goemaere S, Veys EM. Source: Osteoarthritis and Cartilage / Oars, Osteoarthritis Research Society. 1998 May; 6 Suppl A: 37-8. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=9743818&dopt=Abstract
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Chondroitin sulphate composition and structure in alternatively spliced CD44 fusion proteins. Author(s): Piepkorn M, Hovingh P, Bennett KL, Aruffo A, Linker A. Source: The Biochemical Journal. 1997 October 15; 327 ( Pt 2): 499-506. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=9359422&dopt=Abstract
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Chondroitin sulphate inhibits connective tissue mast cells. Author(s): Theoharides TC, Patra P, Boucher W, Letourneau R, Kempuraj D, Chiang G, Jeudy S, Hesse L, Athanasiou A. Source: British Journal of Pharmacology. 2000 November; 131(6): 1039-49. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11082109&dopt=Abstract
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Chondroitin sulphate modification in the alpha4 chain of human recombinant laminin-8 (alpha4beta1gamma1). Author(s): Kortesmaa J, Doi M, Patarroyo M, Tryggvason K. Source: Matrix Biology : Journal of the International Society for Matrix Biology. 2002 October; 21(6): 483-6. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12392759&dopt=Abstract
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Chondroitin sulphate proteoglycans in the CNS injury response. Author(s): Morgenstern DA, Asher RA, Fawcett JW. Source: Prog Brain Res. 2002; 137: 313-32. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12440375&dopt=Abstract
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Chondroitin sulphation patterns in synovial fluid in osteoarthritis subsets. Author(s): Lewis S, Crossman M, Flannelly J, Belcher C, Doherty M, Bayliss MT, Mason RM. Source: Annals of the Rheumatic Diseases. 1999 July; 58(7): 441-5. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10381489&dopt=Abstract
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Chondroitin-4-sulfate protects high-density lipoprotein against copper-dependent oxidation. Author(s): Albertini R, De Luca G, Passi A, Moratti R, Abuja PM. Source: Archives of Biochemistry and Biophysics. 1999 May 1; 365(1): 143-9. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10222048&dopt=Abstract
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Chondroitin-6-sulphate incorporated into collagen gels for the growth of human keratinocytes: the effect of cross-linking agents and diamines. Author(s): Hanthamrongwit M, Reid WH, Grant MH. Source: Biomaterials. 1996 April; 17(8): 775-80. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=8730961&dopt=Abstract
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Chondroitinase ABC (pharmaceutical grade) for chemonucleolysis spine. Author(s): Nordby EJ. Source: Spine. 1997 September 15; 22(18): 2194-5. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=9322333&dopt=Abstract
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Chondroitinase ABC promotes functional recovery after spinal cord injury. Author(s): Bradbury EJ, Moon LD, Popat RJ, King VR, Bennett GS, Patel PN, Fawcett JW, McMahon SB. Source: Nature. 2002 April 11; 416(6881): 636-40. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11948352&dopt=Abstract
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Chondroprotective agents: glucosamine and chondroitin. Author(s): Hungerford MW, Valaik D. Source: Foot Ankle Clin. 2003 June; 8(2): 201-19. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12911236&dopt=Abstract
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Cloning and chromosomal mapping of the human gene of neuroglycan C (NGC), a neural transmembrane chondroitin sulfate proteoglycan with an EGF module. Author(s): Yasuda Y, Tokita Y, Aono S, Matsui F, Ono T, Sonta S, Watanabe E, Nakanishi Y, Oohira A. Source: Neuroscience Research. 1998 December; 32(4): 313-22. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=9950058&dopt=Abstract
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Collagenase activity of cathepsin K depends on complex formation with chondroitin sulfate. Author(s): Li Z, Hou WS, Escalante-Torres CR, Gelb BD, Bromme D. Source: The Journal of Biological Chemistry. 2002 August 9; 277(32): 28669-76. Epub 2002 May 30. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12039963&dopt=Abstract
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Collagenolytic activity of cathepsin K is specifically modulated by cartilage-resident chondroitin sulfates. Author(s): Li Z, Hou WS, Bromme D. Source: Biochemistry. 2000 January 25; 39(3): 529-36. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10642177&dopt=Abstract
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Combined collagen membrane and hydroxyapatite/collagen chondroitin-sulfate spacer placement in the treatment of 2-wall intrabony defects in chronic adult and rapidly progressive periodontitis patients. Author(s): Benque E, Zahedi S, Brocard D, Oscaby F, Justumus P, Brunel G. Source: Journal of Clinical Periodontology. 1997 August; 24(8): 550-6. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=9266342&dopt=Abstract
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Comparison of the antiinflammatory efficacy of chondroitin sulfate and diclofenac sodium in patients with knee osteoarthritis. Author(s): Morreale P, Manopulo R, Galati M, Boccanera L, Saponati G, Bocchi L. Source: The Journal of Rheumatology. 1996 August; 23(8): 1385-91. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=8856618&dopt=Abstract
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Compositional and structural alterations of chondroitin and dermatan sulfates during the progression of atherosclerosis and aneurysmal dilatation of the human abdominal aorta. Author(s): Theocharis AD, Theocharis DA, De Luca G, Hjerpe A, Karamanos NK. Source: Biochimie. 2002 July; 84(7): 667-74. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12453639&dopt=Abstract
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Cooperative role for activated alpha4 beta1 integrin and chondroitin sulfate proteoglycans in cell adhesion to the heparin III domain of fibronectin. Identification of a novel heparin and cell binding sequence in repeat III5. Author(s): Moyano JV, Carnemolla B, Albar JP, Leprini A, Gaggero B, Zardi L, GarciaPardo A. Source: The Journal of Biological Chemistry. 1999 January 1; 274(1): 135-42. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=9867821&dopt=Abstract
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Cortical areas abundant in extracellular matrix chondroitin sulphate proteoglycans are less affected by cytoskeletal changes in Alzheimer's disease. Author(s): Bruckner G, Hausen D, Hartig W, Drlicek M, Arendt T, Brauer K. Source: Neuroscience. 1999; 92(3): 791-805. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10426522&dopt=Abstract
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Cytoadherence characteristics of Plasmodium falciparum isolates from Thailand: evidence for chondroitin sulfate a as a cytoadherence receptor. Author(s): Chaiyaroj SC, Angkasekwinai P, Buranakiti A, Looareesuwan S, Rogerson SJ, Brown GV. Source: The American Journal of Tropical Medicine and Hygiene. 1996 July; 55(1): 76-80. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=8702026&dopt=Abstract
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Cytoadherence of Plasmodium falciparum to intercellular adhesion molecule 1 and chondroitin-4-sulfate expressed by the syncytiotrophoblast in the human placenta. Author(s): Maubert B, Guilbert LJ, Deloron P. Source: Infection and Immunity. 1997 April; 65(4): 1251-7. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=9119459&dopt=Abstract
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Degradation of chondroitin sulfate and dermatan sulfate with chondroitin lyases. Author(s): Hernaiz MJ, Linhardt RJ. Source: Methods in Molecular Biology (Clifton, N.J.). 2001; 171: 363-71. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11450250&dopt=Abstract
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Dermatan is a better substrate for 4-O-sulfation than chondroitin: implications in the generation of 4-O-sulfated, L-iduronate-rich galactosaminoglycans. Author(s): Eklund E, Roden L, Malmstrom M, Malmstrom A. Source: Archives of Biochemistry and Biophysics. 2000 November 15; 383(2): 171-7. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11185550&dopt=Abstract
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Detection and possible biological role of chondroitinase and heparitinase enzymes produced by Porphyromonas gingivalis W50. Author(s): Smith AJ, Greenman J, Embery G. Source: Journal of Periodontal Research. 1997 January; 32(1 Pt 1): 1-8. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=9085237&dopt=Abstract
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Determining the efficacy of glucosamine and chondroitin for osteoarthritis. Author(s): O'Rourke M. Source: The Nurse Practitioner. 2001 June; 26(6): 44-6, 49-52. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11416939&dopt=Abstract
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Development of antibodies against chondroitin sulfate A-adherent Plasmodium falciparum in pregnant women. Author(s): Maubert B, Fievet N, Tami G, Cot M, Boudin C, Deloron P. Source: Infection and Immunity. 1999 October; 67(10): 5367-71. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10496918&dopt=Abstract
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Developmental changes in serum UDP-GlcA:chondroitin glucuronyltransferase activity. Author(s): Kitagawa H, Ujikawa M, Sugahara K. Source: The Journal of Biological Chemistry. 1996 March 22; 271(12): 6583-5. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=8636071&dopt=Abstract
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Differential effects of chondroitin sulfates A and B on monocyte and B-cell activation: evidence for B-cell activation via a CD44-dependent pathway. Author(s): Rachmilewitz J, Tykocinski ML. Source: Blood. 1998 July 1; 92(1): 223-9. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=9639520&dopt=Abstract
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Differential roles of two N-acetylgalactosaminyltransferases, CSGalNAcT-1, and a novel enzyme, CSGalNAcT-2. Initiation and elongation in synthesis of chondroitin sulfate. Author(s): Sato T, Gotoh M, Kiyohara K, Akashima T, Iwasaki H, Kameyama A, Mochizuki H, Yada T, Inaba N, Togayachi A, Kudo T, Asada M, Watanabe H, Imamura T, Kimata K, Narimatsu H. Source: The Journal of Biological Chemistry. 2003 January 31; 278(5): 3063-71. Epub 2002 November 20. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12446672&dopt=Abstract
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Disaccharide analysis of chondroitin sulfate in peri-implant sulcus fluid from dental implants. Author(s): Okazaki J, Gonda Y, Kamada A, Sakaki T, Kitayama N, Kawamura T, Ueda M. Source: European Journal of Oral Sciences. 1996 April; 104(2 ( Pt 1)): 141-3. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=8804903&dopt=Abstract
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Disaccharide composition of hyaluronan and chondroitin/dermatan sulfate. Analysis with fluorophore-assisted carbohydrate electrophoresis. Author(s): Plaas AH, West L, Midura RJ, Hascall VC. Source: Methods in Molecular Biology (Clifton, N.J.). 2001; 171: 117-28. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11450222&dopt=Abstract
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Distribution of hyaluronan and dermatan/chondroitin sulfate proteoglycans in human aortic dissection. Author(s): Gutierrez PS, Reis MM, Higuchi ML, Aiello VD, Stolf NA, Lopes EA. Source: Connective Tissue Research. 1998; 37(3-4): 151-61. Erratum In: Connect Tissue Res 1999; 40(3): 233. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=9862217&dopt=Abstract
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Do glucosamine and chondroitin treat the symptoms of osteoarthritis? Author(s): Edelist DD, Evans MF. Source: Can Fam Physician. 2001 February; 47: 275-7. No Abstract Available. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11228027&dopt=Abstract
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Do glucosamine or chondroitin cause regeneration of cartilage in osteoarthritis? Author(s): Priebe D, McDiarmid T, Mackler L, Tudiver F. Source: The Journal of Family Practice. 2003 March; 52(3): 237-9. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12620182&dopt=Abstract
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Does chondroitin sulfate defend the human uterine cervix against ripening in threatened premature labor? Author(s): Obara M, Hirano H, Ogawa M, Tsubaki H, Yoshida Y, Miyauchi S, Tanaka T. Source: American Journal of Obstetrics and Gynecology. 2000 February; 182(2): 334-9. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10694333&dopt=Abstract
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Effect of chondroitinase ABC on purulent sputum from cystic fibrosis and other patients. Author(s): Khatri IA, Bhaskar KR, Lamont JT, Sajjan SU, Ho CK, Forstner J. Source: Pediatric Research. 2003 April; 53(4): 619-27. Epub 2003 January 15. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12612214&dopt=Abstract
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Effects of chondroitin sulfate and interleukin-1 beta on human articular chondrocytes cultivated in clusters. Author(s): Bassleer CT, Combal JP, Bougaret S, Malaise M. Source: Osteoarthritis and Cartilage / Oars, Osteoarthritis Research Society. 1998 May; 6(3): 196-204. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=9682786&dopt=Abstract
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Effects of chondroitin sulfate and interleukin-1beta on human chondrocyte cultures exposed to pressurization: a biochemical and morphological study. Author(s): Nerucci F, Fioravanti A, Cicero MR, Collodel G, Marcolongo R. Source: Osteoarthritis and Cartilage / Oars, Osteoarthritis Research Society. 2000 July; 8(4): 279-87. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10903882&dopt=Abstract
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Effects of mitogens on synthesis and distribution of heparan and chondroitin sulphates by human leukemic B, T cells and monocytes studied by high-performance liquid chromatography and radiochemical detection. Author(s): Makatsori E, Tsegenidis T, Karamanos NK. Source: Biomedical Chromatography : Bmc. 2001 December; 15(8): 534-8. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11748689&dopt=Abstract
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Effects of oral chondroitin sulfate on the progression of knee osteoarthritis: a pilot study. Author(s): Uebelhart D, Thonar EJ, Delmas PD, Chantraine A, Vignon E. Source: Osteoarthritis and Cartilage / Oars, Osteoarthritis Research Society. 1998 May; 6 Suppl A: 39-46. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=9743819&dopt=Abstract
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Efficacy and tolerability of chondroitin sulfate 1200 mg/day vs chondroitin sulfate 3 x 400 mg/day vs placebo. Author(s): Bourgeois P, Chales G, Dehais J, Delcambre B, Kuntz JL, Rozenberg S. Source: Osteoarthritis and Cartilage / Oars, Osteoarthritis Research Society. 1998 May; 6 Suppl A: 25-30. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=9743816&dopt=Abstract
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Efficacy and tolerability of oral chondroitin sulfate as a symptomatic slow-acting drug for osteoarthritis (SYSADOA) in the treatment of knee osteoarthritis. Author(s): Bucsi L, Poor G. Source: Osteoarthritis and Cartilage / Oars, Osteoarthritis Research Society. 1998 May; 6 Suppl A: 31-6. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=9743817&dopt=Abstract
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Efficacy of a combination of FCHG49 glucosamine hydrochloride, TRH122 low molecular weight sodium chondroitin sulfate and manganese ascorbate in the management of knee osteoarthritis. Author(s): Das A Jr, Hammad TA. Source: Osteoarthritis and Cartilage / Oars, Osteoarthritis Research Society. 2000 September; 8(5): 343-50. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10966840&dopt=Abstract
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Efficacy of glucosamine and chondroitin for treatment of osteoarthritis. Author(s): Donohoe M. Source: Jama : the Journal of the American Medical Association. 2000 September 13; 284(10): 1241; Author Reply 1242. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10979100&dopt=Abstract
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Efficacy of glucosamine and chondroitin for treatment of osteoarthritis. Author(s): Mautone G. Source: Jama : the Journal of the American Medical Association. 2000 September 13; 284(10): 1241; Author Reply 1242. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10979099&dopt=Abstract
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Elevated levels of peritumoral chondroitin sulfate are predictive of poor prognosis in patients treated by radical prostatectomy for early-stage prostate cancer. Author(s): Ricciardelli C, Quinn DI, Raymond WA, McCaul K, Sutherland PD, Stricker PD, Grygiel JJ, Sutherland RL, Marshall VR, Tilley WD, Horsfall DJ. Source: Cancer Research. 1999 May 15; 59(10): 2324-8. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10344737&dopt=Abstract
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Elevated stromal chondroitin sulfate glycosaminoglycan predicts progression in early-stage prostate cancer. Author(s): Ricciardelli C, Mayne K, Sykes PJ, Raymond WA, McCaul K, Marshall VR, Tilley WD, Skinner JM, Horsfall DJ. Source: Clinical Cancer Research : an Official Journal of the American Association for Cancer Research. 1997 June; 3(6): 983-92. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=9815775&dopt=Abstract
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Endocan is a novel chondroitin sulfate/dermatan sulfate proteoglycan that promotes hepatocyte growth factor/scatter factor mitogenic activity. Author(s): Bechard D, Gentina T, Delehedde M, Scherpereel A, Lyon M, Aumercier M, Vazeux R, Richet C, Degand P, Jude B, Janin A, Fernig DG, Tonnel AB, Lassalle P. Source: The Journal of Biological Chemistry. 2001 December 21; 276(51): 48341-9. Epub 2001 October 05. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11590178&dopt=Abstract
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Enzymatic synthesis of chondroitin with a novel chondroitin sulfate Nacetylgalactosaminyltransferase that transfers N-acetylgalactosamine to glucuronic acid in initiation and elongation of chondroitin sulfate synthesis. Author(s): Gotoh M, Sato T, Akashima T, Iwasaki H, Kameyama A, Mochizuki H, Yada T, Inaba N, Zhang Y, Kikuchi N, Kwon YD, Togayachi A, Kudo T, Nishihara S, Watanabe H, Kimata K, Narimatsu H. Source: The Journal of Biological Chemistry. 2002 October 11; 277(41): 38189-96. Epub 2002 August 05. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12163485&dopt=Abstract
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Ex vivo desequestration of Plasmodium falciparum-infected erythrocytes from human placenta by chondroitin sulfate A. Author(s): Gysin J, Pouvelle B, Fievet N, Scherf A, Lepolard C. Source: Infection and Immunity. 1999 December; 67(12): 6596-602. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10569780&dopt=Abstract
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Experience with i.v. iron chondroitin-sulphate colloid in Japanese haemodialysis patients. Author(s): Shimamatsu K. Source: Nephrology, Dialysis, Transplantation : Official Publication of the European Dialysis and Transplant Association - European Renal Association. 1998 April; 13(4): 1053. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=9568888&dopt=Abstract
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Expression and characterization of the IPM 150 gene (IMPG1) product, a novel human photoreceptor cell-associated chondroitin-sulfate proteoglycan. Author(s): Kuehn MH, Hageman GS. Source: Matrix Biology : Journal of the International Society for Matrix Biology. 1999 October; 18(5): 509-18. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10601738&dopt=Abstract
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Expression of heparan sulphate and small dermatan/chondroitin sulphate proteoglycans in chronically inflamed human periodontium. Author(s): Oksala O, Haapasalmi K, Hakkinen L, Uitto VJ, Larjava H. Source: Journal of Dental Research. 1997 June; 76(6): 1250-9. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=9168858&dopt=Abstract
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Expression of small extracellular chondroitin/dermatan sulfate proteoglycans is differentially regulated in human endothelial cells. Author(s): Nelimarkka L, Kainulainen V, Schonherr E, Moisander S, Jortikka M, Lammi M, Elenius K, Jalkanen M, Jarvelainen H. Source: The Journal of Biological Chemistry. 1997 May 9; 272(19): 12730-7. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=9139731&dopt=Abstract
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Fibrillin: evidence that chondroitin sulphate proteoglycans are components of microfibrils and associate with newly synthesised monomers. Author(s): Kielty CM, Whittaker SP, Shuttleworth CA. Source: Febs Letters. 1996 May 20; 386(2-3): 169-73. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=8647274&dopt=Abstract
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Fibronectin and laminin elicit differential behaviors from SH-SY5Y growth cones contacting inhibitory chondroitin sulfate proteoglycans. Author(s): Hynds DL, Snow DM. Source: Journal of Neuroscience Research. 2001 November 15; 66(4): 630-42. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11746383&dopt=Abstract
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From oranges and lemons to glucosamine and chondroitin sulfate: clinical observations stimulate basic research. Author(s): Buckwalter JA, Callaghan JJ, Rosier RN. Source: The Journal of Bone and Joint Surgery. American Volume. 2001 August; 83-A(8): 1266-8. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11507135&dopt=Abstract
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Functional expression and genomic structure of human chondroitin 6sulfotransferase. Author(s): Tsutsumi K, Shimakawa H, Kitagawa H, Sugahara K. Source: Febs Letters. 1998 December 18; 441(2): 235-41. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=9883891&dopt=Abstract
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Galectin 1 inhibits incorporation of vitronectin and chondroitin sulfate B into the extracellular matrix of human vascular smooth muscle cells. Author(s): Moiseeva EP, Williams B, Samani NJ. Source: Biochimica Et Biophysica Acta. 2003 January 20; 1619(2): 125-32. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12527107&dopt=Abstract
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Gelatin/chondroitin 6-sulfate microspheres for the delivery of therapeutic proteins to the joint. Author(s): Brown KE, Leong K, Huang CH, Dalal R, Green GD, Haimes HB, Jimenez PA, Bathon J. Source: Arthritis and Rheumatism. 1998 December; 41(12): 2185-95. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=9870875&dopt=Abstract
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Gene expression of matrix metalloproteinase-1 (interstitial collagenase) and matrix metalloproteinase-3 (stromelysin-1) in basal cell carcinoma by in situ hybridization using chondroitin ABC lyase. Author(s): Tsukifuji R, Sakai Y, Hatamochi A, Shinkai H. Source: The Histochemical Journal. 1997 May; 29(5): 401-7. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=9184854&dopt=Abstract
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Generation of artificial proteoglycans containing glycosaminoglycan-modified CD44. Demonstration of the interaction between rantes and chondroitin sulfate. Author(s): Wolff EA, Greenfield B, Taub DD, Murphy WJ, Bennett KL, Aruffo A. Source: The Journal of Biological Chemistry. 1999 January 22; 274(4): 2518-24. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=9891023&dopt=Abstract
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Glucosamine and chondroitin for osteoarthritis. Author(s): Akama H, Saito S. Source: Arthritis and Rheumatism. 2001 February; 45(1): 107. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11308055&dopt=Abstract
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Glucosamine and chondroitin for osteoarthritis? Author(s): McAlindon T. Source: Bulletin on the Rheumatic Diseases. 2001 July; 50(7): 1-4. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11530541&dopt=Abstract
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Glucosamine and chondroitin for treating symptoms of osteoarthritis: evidence is widely touted but incomplete. Author(s): Towheed TE, Anastassiades TP. Source: Jama : the Journal of the American Medical Association. 2000 March 15; 283(11): 1483-4. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10732941&dopt=Abstract
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Glucosamine and chondroitin for treatment of osteoarthritis: a systematic quality assessment and meta-analysis. Author(s): McAlindon TE, LaValley MP, Gulin JP, Felson DT. Source: Jama : the Journal of the American Medical Association. 2000 March 15; 283(11): 1469-75. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10732937&dopt=Abstract
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Glucosamine and chondroitin may help in osteoarthritis. Author(s): Walker-Bone K, Javid K, Arden N, Cooper C. Source: Bmj (Clinical Research Ed.). 2001 March 17; 322(7287): 673. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11250841&dopt=Abstract
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Glucosamine and chondroitin sulfate are effective in the management of osteoarthritis. Author(s): Hungerford DS, Jones LC. Source: The Journal of Arthroplasty. 2003 April; 18(3 Suppl 1): 5-9. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12730919&dopt=Abstract
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Glucosamine and chondroitin sulfate for the treatment of osteoarthritis: comment on the article by Akama and Saito. Author(s): Leeb BF. Source: Arthritis and Rheumatism. 2001 December; 45(6): 537-8. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11762688&dopt=Abstract
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Glucosamine and chondroitin sulfates in the treatment of osteoarthritis: a survey. Author(s): de los Reyes GC, Koda RT, Lien EJ. Source: Prog Drug Res. 2000; 55: 81-103. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11127967&dopt=Abstract
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Glucosamine and chondroitin were found to improve outcomes in patients with osteoarthritis. Author(s): Kreder HJ. Source: The Journal of Bone and Joint Surgery. American Volume. 2000 September; 82(9): 1323. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11005524&dopt=Abstract
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Glucosamine, chondroitin, and manganese ascorbate for degenerative joint disease of the knee or low back: a randomized, double-blind, placebo-controlled pilot study. Author(s): Leffler CT, Philippi AF, Leffler SG, Mosure JC, Kim PD. Source: Military Medicine. 1999 February; 164(2): 85-91. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10050562&dopt=Abstract
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Glycans as endocytosis signals: the cases of the asialoglycoprotein and hyaluronan/chondroitin sulfate receptors. Author(s): Weigel PH, Yik JH. Source: Biochimica Et Biophysica Acta. 2002 September 19; 1572(2-3): 341-63. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12223279&dopt=Abstract
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Glycosaminoglycan sulfation in human osteoarthritis. Disease-related alterations at the non-reducing termini of chondroitin and dermatan sulfate. Author(s): Plaas AH, West LA, Wong-Palms S, Nelson FR. Source: The Journal of Biological Chemistry. 1998 May 15; 273(20): 12642-9. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=9575226&dopt=Abstract
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Gravidity-dependent production of antibodies that inhibit binding of Plasmodium falciparum-infected erythrocytes to placental chondroitin sulfate proteoglycan during pregnancy. Author(s): O'Neil-Dunne I, Achur RN, Agbor-Enoh ST, Valiyaveettil M, Naik RS, Ockenhouse CF, Zhou A, Megnekou R, Leke R, Taylor DW, Gowda DC. Source: Infection and Immunity. 2001 December; 69(12): 7487-92. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11705924&dopt=Abstract
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Heparan sulfate and chondroitin sulfate proteoglycans inhibit E-selectin binding to endothelial cells. Author(s): Luo J, Kato M, Wang H, Bernfield M, Bischoff J. Source: Journal of Cellular Biochemistry. 2001; 80(4): 522-31. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11169736&dopt=Abstract
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Heparan/chondroitin sulfate biosynthesis. Structure and mechanism of human glucuronyltransferase I. Author(s): Pedersen LC, Tsuchida K, Kitagawa H, Sugahara K, Darden TA, Negishi M. Source: The Journal of Biological Chemistry. 2000 November 3; 275(44): 34580-5. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10946001&dopt=Abstract
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Heparan/chondroitin/dermatan sulfate primer 2-(6-hydroxynaphthyl)-O-beta-Dxylopyranoside preferentially inhibits growth of transformed cells. Author(s): Mani K, Havsmark B, Persson S, Kaneda Y, Yamamoto H, Sakurai K, Ashikari S, Habuchi H, Suzuki S, Kimata K, Malmstrom A, Westergren-Thorsson G, Fransson LA. Source: Cancer Research. 1998 March 15; 58(6): 1099-104. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=9515787&dopt=Abstract
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Hepatocellular carcinoma exhibiting a concentric structure of different histologic grades: evaluation by chondroitin sulfate iron colloid-enhanced MR imaging. Author(s): Kamba M, Suto Y, Kodama F, Ohta Y, Kobayashi J, Horie Y, Kawasaki H. Source: Journal of Magnetic Resonance Imaging : Jmri. 1996 March-April; 6(2): 406-8. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=8859586&dopt=Abstract
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Heterogeneity of the chondroitin sulfate portion of phosphacan/6B4 proteoglycan regulates its binding affinity for pleiotrophin/heparin binding growth-associated molecule. Author(s): Maeda N, He J, Yajima Y, Mikami T, Sugahara K, Yabe T. Source: The Journal of Biological Chemistry. 2003 September 12; 278(37): 35805-11. Epub 2003 July 02. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12840014&dopt=Abstract
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High affinity of a fucosylated chondroitin sulfate for plasma low density lipoprotein. Author(s): Tovar AM, Mourao PA. Source: Atherosclerosis. 1996 October 25; 126(2): 185-95. Erratum In: Atherosclerosis 1997 February 10; 128(2): 255-6. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=8902144&dopt=Abstract
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High-performance liquid chromatography analysis of chondroitin sulphate isomers in human whole saliva in a variety of clinical conditions. Author(s): Okazaki J, Kamada A, Gonda Y, Sakaki T, Embery G. Source: Oral Diseases. 1996 September; 2(3): 224-7. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=9081763&dopt=Abstract
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Human chondroitin 6-sulfotransferase: cloning, gene structure, and chromosomal localization. Author(s): Mazany KD, Peng T, Watson CE, Tabas I, Williams KJ. Source: Biochimica Et Biophysica Acta. 1998 July 1; 1407(1): 92-7. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=9639683&dopt=Abstract
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Human melanoma/NG2 chondroitin sulfate proteoglycan is expressed in the sarcolemma of postnatal human skeletal myofibers. Abnormal expression in merosinnegative and Duchenne muscular dystrophies. Author(s): Petrini S, Tessa A, Carrozzo R, Verardo M, Pierini R, Rizza T, Bertini E. Source: Molecular and Cellular Neurosciences. 2003 June; 23(2): 219-31. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12812755&dopt=Abstract
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Human osteoarthritic cartilage exhibits the 2B6 epitope without pretreatment with chondroitinase ABC. Author(s): Asari A, Akizaki S, Itoh T, Kominami E, Uchiyama Y. Source: Osteoarthritis and Cartilage / Oars, Osteoarthritis Research Society. 1996 June; 4(2): 149-52. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=8806117&dopt=Abstract
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Human single-chain Fv immunoconjugates targeted to a melanoma-associated chondroitin sulfate proteoglycan mediate specific lysis of human melanoma cells by natural killer cells and complement. Author(s): Wang B, Chen YB, Ayalon O, Bender J, Garen A. Source: Proceedings of the National Academy of Sciences of the United States of America. 1999 February 16; 96(4): 1627-32. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=9990075&dopt=Abstract
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Hyaluronic acid and chondroitin sulphate A rapidly promote differentiation of immature DC with upregulation of costimulatory and antigen-presenting molecules, and enhancement of NF-kappaB and protein kinase activity. Author(s): Yang R, Yan Z, Chen F, Hansson GK, Kiessling R. Source: Scandinavian Journal of Immunology. 2002 January; 55(1): 2-13. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11841687&dopt=Abstract
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Identification and characterization of ligands for L-selectin in the kidney. I. Versican, a large chondroitin sulfate proteoglycan, is a ligand for L-selectin. Author(s): Kawashima H, Li YF, Watanabe N, Hirose J, Hirose M, Miyasaka M. Source: International Immunology. 1999 March; 11(3): 393-405. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10221651&dopt=Abstract
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Identification of glycosaminoglycan binding domains in Plasmodium falciparum erythrocyte membrane protein 1 of a chondroitin sulfate A-adherent parasite. Author(s): Reeder JC, Hodder AN, Beeson JG, Brown GV. Source: Infection and Immunity. 2000 July; 68(7): 3923-6. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10858204&dopt=Abstract
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Identification of the human melanoma-associated chondroitin sulfate proteoglycan antigen epitope recognized by the antitumor monoclonal antibody 763.74 from a peptide phage library. Author(s): Geiser M, Schultz D, Le Cardinal A, Voshol H, Garcia-Echeverria C. Source: Cancer Research. 1999 February 15; 59(4): 905-10. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10029083&dopt=Abstract
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Immunization with recombinant duffy binding-like-gamma3 induces pan-reactive and adhesion-blocking antibodies against placental chondroitin sulfate A-binding Plasmodium falciparum parasites. Author(s): Costa FT, Fusai T, Parzy D, Sterkers Y, Torrentino M, Douki JB, Traore B, Petres S, Scherf A, Gysin J. Source: The Journal of Infectious Diseases. 2003 July 1; 188(1): 153-64. Epub 2003 June 23. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12825185&dopt=Abstract
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Immunohistochemical localization of large chondroitin sulfate proteoglycan in odontogenic tumor. Author(s): Ito Y, Abiko Y, Tanaka Y, Rahemtulla F, Kaku T. Source: Medical Electron Microscopy : Official Journal of the Clinical Electron Microscopy Society of Japan. 2002 September; 35(3): 173-7. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12353139&dopt=Abstract
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Immunohistochemical study of chondroitin-6-sulphate and tenascin in the larynx: a loss of chondroitin-6-sulphate expression accompanies squamous cell carcinoma invasion. Author(s): Uhlman DL, Niehans GA. Source: The Journal of Pathology. 1999 December; 189(4): 470-4. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10629545&dopt=Abstract
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Immunohistological distribution of heparan sulfate proteoglycan and chondroitin 6sulfate in carcinomas with eccrine differentiation. Author(s): Kazama T, Isemura M, Nakamura T, Ito M. Source: Archives of Dermatological Research. 1996 October; 288(11): 718-21. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=8931877&dopt=Abstract
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Immunolocalization of keratan sulfate, chondroitin-4-sulfate, and chondroitin-6sulfate in periprosthetic breast capsules exhibiting synovial metaplasia. Author(s): Raso DS, Schulte BA. Source: Plastic and Reconstructive Surgery. 1996 July; 98(1): 78-82. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=8657791&dopt=Abstract
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Importance of GlcUAbeta1-3GalNAc(4S,6S) in chondroitin sulfate E for t-PA- and uPA-mediated Glu-plasminogen activation. Author(s): Sakai T, Kyogashima M, Kariya Y, Urano T, Takada Y, Takada A. Source: Thrombosis Research. 2000 December 15; 100(6): 557-65. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11152936&dopt=Abstract
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In vitro action of a combination of selected antimicrobial agents and chondroitin sulfate. Author(s): Muller G, Kramer A. Source: Chemico-Biological Interactions. 2000 January 15; 124(2): 77-85. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10670820&dopt=Abstract
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In vitro and in vivo evaluation of gelatin-chondroitin sulphate hydrogels for controlled release of antibacterial proteins. Author(s): Kuijpers AJ, van Wachem PB, van Luyn MJ, Brouwer LA, Engbers GH, Krijgsveld J, Zaat SA, Dankert J, Feijen J. Source: Biomaterials. 2000 September; 21(17): 1763-72. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10905458&dopt=Abstract
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Inactivation of thrombin by a fucosylated chondroitin sulfate from echinoderm. Author(s): Mourao PA, Boisson-Vidal C, Tapon-Bretaudiere J, Drouet B, Bros A, Fischer A. Source: Thrombosis Research. 2001 April 15; 102(2): 167-76. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11323028&dopt=Abstract
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Incidental improvement of breast capsular contracture following treatment of arthritis with glucosamine and chondroitin. Author(s): Skillman JM, Ahmed OA, Rowsell AR. Source: British Journal of Plastic Surgery. 2002 July; 55(5): 454. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12372385&dopt=Abstract
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Increased urine heparan and chondroitin sulphate excretion in patients with osteopetrosis. Author(s): Steiner RD, Whyte MP, Chang E, Hanks J, Mattes C, Senephansiri H, Gibson KM. Source: Journal of Inherited Metabolic Disease. 2000 February; 23(1): 88-90. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10682314&dopt=Abstract
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Influence of chondroitin sulfate charge density, sulfate group position, and molecular mass on Cu2+-mediated oxidation of human low-density lipoproteins: effect of normal human plasma-derived chondroitin sulfate. Author(s): Volpi N, Tarugi P. Source: Journal of Biochemistry. 1999 February; 125(2): 297-304. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=9990126&dopt=Abstract
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Inhibition of binding of malaria-infected erythrocytes by a tetradecasaccharide fraction from chondroitin sulfate A. Author(s): Beeson JG, Chai W, Rogerson SJ, Lawson AM, Brown GV. Source: Infection and Immunity. 1998 July; 66(7): 3397-402. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=9632611&dopt=Abstract
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Inhibition of human leukocyte elastase activity by chondroitin sulfates. Author(s): Volpi N. Source: Chemico-Biological Interactions. 1997 August 1; 105(3): 157-67. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=9291994&dopt=Abstract
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Inhibitory activity of human lactoferrin and its peptide on chondroitin sulfate A-, CD36-, and thrombospondin-mediated cytoadherence of plasmodium falciparuminfected erythrocytes. Author(s): Eda S, Eda K, Prudhomme JG, Sherman IW. Source: Blood. 1999 July 1; 94(1): 326-32. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10381529&dopt=Abstract
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Initial characterization of the vitamin D binding protein (Gc-globulin) binding site on the neutrophil plasma membrane: evidence for a chondroitin sulfate proteoglycan. Author(s): DiMartino SJ, Kew RR. Source: Journal of Immunology (Baltimore, Md. : 1950). 1999 August 15; 163(4): 2135-42. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10438954&dopt=Abstract
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Interactions between chitosan and glycosaminoglycans (chondroitin sulfate and hyaluronic acid): physicochemical and biological studies. Author(s): Denuziere A, Ferrier D, Domard A. Source: Annales Pharmaceutiques Francaises. 2000 January; 58(1): 47-53. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10669813&dopt=Abstract
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Interferon gamma differentially affects the synthesis of chondroitin/dermatan sulphate and heparan sulphate by human skin fibroblasts. Author(s): Praillet C, Lortat-Jacob H, Grimaud JA. Source: The Biochemical Journal. 1996 September 15; 318 ( Pt 3): 863-70. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=8836130&dopt=Abstract
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Intra-articular levels of prostaglandin E2, hyaluronic acid, and chondroitin-4 and -6 sulfates in the temporomandibular joint synovial fluid of patients with internal derangement. Author(s): Murakami KI, Shibata T, Kubota E, Maeda H. Source: Journal of Oral and Maxillofacial Surgery : Official Journal of the American Association of Oral and Maxillofacial Surgeons. 1998 February; 56(2): 199-203. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=9461145&dopt=Abstract
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Intracellular coupling of the heavy chain of pre-alpha-inhibitor to chondroitin sulfate. Author(s): Kaczmarczyk A, Thuveson M, Fries E. Source: The Journal of Biological Chemistry. 2002 April 19; 277(16): 13578-82. Epub 2002 February 04. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11827976&dopt=Abstract
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Investigation into the biological stability of collagen/chondroitin-6-sulphate gels and their contraction by fibroblasts and keratinocytes: the effect of crosslinking agents and diamines. Author(s): Osborne CS, Reid WH, Grant MH. Source: Biomaterials. 1999 February; 20(3): 283-90. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10030605&dopt=Abstract
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Involvement of chondroitin sulfates on brain-derived tenascin-R in carbohydratedependent interactions with fibronectin and tenascin-C. Author(s): Probstmeier R, Braunewell K, Pesheva P. Source: Brain Research. 2000 April 28; 863(1-2): 42-51. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10773191&dopt=Abstract
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Involvement of the core protein in the first beta-N-acetylgalactosamine transfer to the glycosaminoglycan-protein linkage-region tetrasaccharide and in the subsequent polymerization: the critical determining step for chondroitin sulphate biosynthesis. Author(s): Nadanaka S, Kitagawa H, Goto F, Tamura J, Neumann KW, Ogawa T, Sugahara K. Source: The Biochemical Journal. 1999 June 1; 340 ( Pt 2): 353-7. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10333474&dopt=Abstract
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Levels of chondroitin sulfate isomers in synovial fluid of patients with hip osteoarthritis. Author(s): Yamada H, Miyauchi S, Hotta H, Morita M, Yoshihara Y, Kikuchi T, Fujikawa K. Source: Journal of Orthopaedic Science : Official Journal of the Japanese Orthopaedic Association. 1999; 4(4): 250-4. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10436271&dopt=Abstract
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Localization and characterization of melanoma-associated glycosaminoglycans: differential expression of chondroitin and heparan sulfate epitopes in melanoma. Author(s): Smetsers TF, van de Westerlo EM, ten Dam GB, Clarijs R, Versteeg EM, van Geloof WL, Veerkamp JH, van Muijen GN, van Kuppevelt TH. Source: Cancer Research. 2003 June 1; 63(11): 2965-70. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12782604&dopt=Abstract
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Localization of keratan sulphate and chondroitin-6-sulphate on the anteriorly displaced human temporomandibular joint disc--histological and immunohistochemical analysis. Author(s): Fujita S, Iizuka T, Dauber W. Source: Journal of Oral Rehabilitation. 2001 October; 28(10): 962-70. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11737569&dopt=Abstract
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Long term response in a patient with neoplastic meningitis secondary to melanoma treated with (131)I-radiolabeled antichondroitin proteoglycan sulfate Mel-14 F(ab')(2): a case study. Author(s): Cokgor I, Akabani G, Friedman HS, Friedman AH, Zalutsky MR, Zehngebot LM, Provenzale JM, Guy CD, Wikstrand CJ, Bigner DD. Source: Cancer. 2001 May 1; 91(9): 1809-13. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11335907&dopt=Abstract
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Macrophage plasma membrane chondroitin sulfate proteoglycan binds oxidized lowdensity lipoprotein. Author(s): Kaplan M, Aviram M. Source: Atherosclerosis. 2000 March; 149(1): 5-17. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10704609&dopt=Abstract
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Macrophages secrete matrix metalloproteinase 9 covalently linked to the core protein of chondroitin sulphate proteoglycans. Author(s): Winberg JO, Kolset SO, Berg E, Uhlin-Hansen L. Source: Journal of Molecular Biology. 2000 December 8; 304(4): 669-80. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11099388&dopt=Abstract
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Malaria during pregnancy: parasites, antibodies and chondroitin sulphate A. Author(s): Duffy PE, Fried M. Source: Biochemical Society Transactions. 1999 August; 27(4): 478-82. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10917625&dopt=Abstract
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Melanoma chondroitin sulfate proteoglycan regulates matrix metalloproteinasedependent human melanoma invasion into type I collagen. Author(s): Iida J, Pei D, Kang T, Simpson MA, Herlyn M, Furcht LT, McCarthy JB. Source: The Journal of Biological Chemistry. 2001 June 1; 276(22): 18786-94. Epub 2001 March 06. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11278606&dopt=Abstract
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Melanoma chondroitin sulphate proteoglycan regulates cell spreading through Cdc42, Ack-1 and p130cas. Author(s): Eisenmann KM, McCarthy JB, Simpson MA, Keely PJ, Guan JL, Tachibana K, Lim L, Manser E, Furcht LT, Iida J. Source: Nature Cell Biology. 1999 December; 1(8): 507-13. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10587647&dopt=Abstract
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Microanalysis of enzyme digests of hyaluronan and chondroitin/dermatan sulfate by fluorophore-assisted carbohydrate electrophoresis (FACE). Author(s): Calabro A, Benavides M, Tammi M, Hascall VC, Midura RJ. Source: Glycobiology. 2000 March; 10(3): 273-81. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10704526&dopt=Abstract
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Modeling of Plasmodium falciparum-infected erythrocyte cytoadhesion in microvascular conditions: chondroitin-4-sulfate binding, A competitive phenotype. Author(s): Pouvelle B, Traore B, Nogueira PA, Pradines B, LePolard C, Gysin J. Source: The Journal of Infectious Diseases. 2003 January 15; 187(2): 292-302. Epub 2002 December 30. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12552454&dopt=Abstract
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Modulation of vascular human endothelial and rat smooth muscle cell growth by a fucosylated chondroitin sulfate from echinoderm. Author(s): Tapon-Bretaudiere J, Drouet B, Matou S, Mourao PA, Bros A, Letourneur D, Fischer AM. Source: Thrombosis and Haemostasis. 2000 August; 84(2): 332-7. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10959709&dopt=Abstract
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Molecular cloning and characterization of a human uronyl 2-sulfotransferase that sulfates iduronyl and glucuronyl residues in dermatan/chondroitin sulfate. Author(s): Kobayashi M, Sugumaran G, Liu J, Shworak NW, Silbert JE, Rosenberg RD. Source: The Journal of Biological Chemistry. 1999 April 9; 274(15): 10474-80. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10187838&dopt=Abstract
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Molecular cloning and characterization of a novel chondroitin sulfate glucuronyltransferase that transfers glucuronic acid to N-acetylgalactosamine. Author(s): Gotoh M, Yada T, Sato T, Akashima T, Iwasaki H, Mochizuki H, Inaba N, Togayachi A, Kudo T, Watanabe H, Kimata K, Narimatsu H. Source: The Journal of Biological Chemistry. 2002 October 11; 277(41): 38179-88. Epub 2002 July 26. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12145278&dopt=Abstract
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Molecular cloning and characterization of chondroitin-4-O-sulfotransferase-3. A novel member of the HNK-1 family of sulfotransferases. Author(s): Kang HG, Evers MR, Xia G, Baenziger JU, Schachner M. Source: The Journal of Biological Chemistry. 2002 September 20; 277(38): 34766-72. Epub 2002 June 21. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12080076&dopt=Abstract
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Molecular cloning and expression of a human chondroitin synthase. Author(s): Kitagawa H, Uyama T, Sugahara K. Source: The Journal of Biological Chemistry. 2001 October 19; 276(42): 38721-6. Epub 2001 August 20. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11514575&dopt=Abstract
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Molecular cloning and expression of a novel chondroitin 6-O-sulfotransferase. Author(s): Kitagawa H, Fujita M, Ito N, Sugahara K. Source: The Journal of Biological Chemistry. 2000 July 14; 275(28): 21075-80. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10781596&dopt=Abstract
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Molecular cloning and expression of a second chondroitin Nacetylgalactosaminyltransferase involved in the initiation and elongation of chondroitin/dermatan sulfate. Author(s): Uyama T, Kitagawa H, Tanaka J, Tamura J, Ogawa T, Sugahara K. Source: The Journal of Biological Chemistry. 2003 January 31; 278(5): 3072-8. Epub 2002 November 13. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12433924&dopt=Abstract
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Molecular cloning and expression of human chondroitin 6-sulfotransferase. Author(s): Fukuta M, Kobayashi Y, Uchimura K, Kimata K, Habuchi O. Source: Biochimica Et Biophysica Acta. 1998 July 30; 1399(1): 57-61. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=9714738&dopt=Abstract
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Molecular cloning and expression of human chondroitin Nacetylgalactosaminyltransferase: the key enzyme for chain initiation and elongation of chondroitin/dermatan sulfate on the protein linkage region tetrasaccharide shared by heparin/heparan sulfate. Author(s): Uyama T, Kitagawa H, Tamura Ji J, Sugahara K. Source: The Journal of Biological Chemistry. 2002 March 15; 277(11): 8841-6. Epub 2002 January 11. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11788602&dopt=Abstract
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Molecular cloning and expression of two distinct human chondroitin 4-Osulfotransferases that belong to the HNK-1 sulfotransferase gene family. Author(s): Hiraoka N, Nakagawa H, Ong E, Akama TO, Fukuda MN, Fukuda M. Source: The Journal of Biological Chemistry. 2000 June 30; 275(26): 20188-96. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10781601&dopt=Abstract
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Molecular cloning of a chondroitin polymerizing factor that cooperates with chondroitin synthase for chondroitin polymerization. Author(s): Kitagawa H, Izumikawa T, Uyama T, Sugahara K. Source: The Journal of Biological Chemistry. 2003 June 27; 278(26): 23666-71. Epub 2003 April 25. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12716890&dopt=Abstract
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Molecular cloning of a human melanoma-associated chondroitin sulfate proteoglycan. Author(s): Pluschke G, Vanek M, Evans A, Dittmar T, Schmid P, Itin P, Filardo EJ, Reisfeld RA. Source: Proceedings of the National Academy of Sciences of the United States of America. 1996 September 3; 93(18): 9710-5. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=8790396&dopt=Abstract
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Molecular cloning, expression, and chromosomal mapping of human chondroitin 4sulfotransferase, whose expression pattern in human tissues is different from that of chondroitin 6-sulfotransferase. Author(s): Okuda T, Mita S, Yamauchi S, Matsubara T, Yagi F, Yamamori D, Fukuta M, Kuroiwa A, Matsuda Y, Habuchi O. Source: Journal of Biochemistry. 2000 November; 128(5): 763-70. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11056388&dopt=Abstract
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Molecular interactions of neural chondroitin sulfate proteoglycans in the brain development. Author(s): Oohira A, Matsui F, Tokita Y, Yamauchi S, Aono S. Source: Archives of Biochemistry and Biophysics. 2000 February 1; 374(1): 24-34. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10640392&dopt=Abstract
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Molecular-weight-dependent pharmacokinetics and cytotoxic properties of cisplatin complexes prepared with chondroitin sulfate A and C. Author(s): Zhang JS, Imai T, Suenaga A, Otagiri M. Source: International Journal of Pharmaceutics. 2002 June 20; 240(1-2): 23-31. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12062498&dopt=Abstract
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Nervous system-derived chondroitin sulfate proteoglycans regulate growth cone morphology and inhibit neurite outgrowth: a light, epifluorescence, and electron microscopy study. Author(s): Snow DM, Mullins N, Hynds DL. Source: Microscopy Research and Technique. 2001 September 1; 54(5): 273-86. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11514984&dopt=Abstract
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Neurite outgrowth inhibition by chondroitin sulfate proteoglycan: stalling/stopping exceeds turning in human neuroblastoma growth cones. Author(s): Hynds DL, Snow DM. Source: Experimental Neurology. 1999 November; 160(1): 244-55. Erratum In: Exp Neurol 2002 May; 175(1): 301. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10630209&dopt=Abstract
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Neurocan: a brain chondroitin sulfate proteoglycan. Author(s): Rauch U, Feng K, Zhou XH. Source: Cellular and Molecular Life Sciences : Cmls. 2001 November; 58(12-13): 1842-56. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11766883&dopt=Abstract
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New approaches to the treatment of osteoarthritis: oral glucosamine and chondroitin sulfate. Author(s): Schenck RC Jr. Source: Instr Course Lect. 2000; 49: 491-4. Review. No Abstract Available. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10829202&dopt=Abstract
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Nonspecific immunoglobulin M binding and chondroitin sulfate A binding are linked phenotypes of Plasmodium falciparum isolates implicated in malaria during pregnancy. Author(s): Creasey AM, Staalsoe T, Raza A, Arnot DE, Rowe JA. Source: Infection and Immunity. 2003 August; 71(8): 4767-71. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12874359&dopt=Abstract
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Novel chondroitin sulfate-binding cationic liposomes loaded with cisplatin efficiently suppress the local growth and liver metastasis of tumor cells in vivo. Author(s): Lee CM, Tanaka T, Murai T, Kondo M, Kimura J, Su W, Kitagawa T, Ito T, Matsuda H, Miyasaka M. Source: Cancer Research. 2002 August 1; 62(15): 4282-8. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12154030&dopt=Abstract
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Nutraceuticals as therapeutic agents in osteoarthritis. The role of glucosamine, chondroitin sulfate, and collagen hydrolysate. Author(s): Deal CL, Moskowitz RW. Source: Rheumatic Diseases Clinics of North America. 1999 May; 25(2): 379-95. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10356424&dopt=Abstract
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Oral absorption and bioavailability of ichthyic origin chondroitin sulfate in healthy male volunteers. Author(s): Volpi N. Source: Osteoarthritis and Cartilage / Oars, Osteoarthritis Research Society. 2003 June; 11(6): 433-41. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12801483&dopt=Abstract
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Oral bioavailability of chondroitin sulfate (Condrosulf) and its constituents in healthy male volunteers. Author(s): Volpi N. Source: Osteoarthritis and Cartilage / Oars, Osteoarthritis Research Society. 2002 October; 10(10): 768-77. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12359162&dopt=Abstract
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Ovarian carcinoma cells synthesize both chondroitin sulfate and heparan sulfate cell surface proteoglycans that mediate cell adhesion to interstitial matrix. Author(s): Kokenyesi R. Source: Journal of Cellular Biochemistry. 2001 August 1-9; 83(2): 259-70. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11573243&dopt=Abstract
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Overexcretion of low-sulphated chondroitin sulphate in the urine of the patient resembling progeroid. Author(s): Inazumi T, Tajima S, Nishikawa T. Source: Dermatology (Basel, Switzerland). 1997; 195(3): 296-300. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=9407187&dopt=Abstract
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Oversulfated chondroitin/dermatan sulfates containing GlcAbeta1/IdoAalpha13GalNAc(4,6-O-disulfate) interact with L- and P-selectin and chemokines. Author(s): Kawashima H, Atarashi K, Hirose M, Hirose J, Yamada S, Sugahara K, Miyasaka M. Source: The Journal of Biological Chemistry. 2002 April 12; 277(15): 12921-30. Epub 2002 January 30. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11821431&dopt=Abstract
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Pancreatic carcinoma is characterized by elevated content of hyaluronan and chondroitin sulfate with altered disaccharide composition. Author(s): Theocharis AD, Tsara ME, Papageorgacopoulou N, Karavias DD, Theocharis DA. Source: Biochimica Et Biophysica Acta. 2000 October 18; 1502(2): 201-6. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11040445&dopt=Abstract
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Patients with head and neck tumors excrete a chondroitin sulfate with a low degree of sulfation: a new tool for diagnosis and follow-up of cancer therapy. Author(s): Martins JR, Gadelha ME, Fonseca SM, Sampaio LO, De L Pontes PA, Dietrich CP, Nader HB. Source: Otolaryngology and Head and Neck Surgery. 2000 January; 122(1): 115-8. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10629497&dopt=Abstract
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Perlecan and basement membrane-chondroitin sulfate proteoglycan (bamacan) are two basement membrane chondroitin/dermatan sulfate proteoglycans in the Engelbreth-Holm-Swarm tumor matrix. Author(s): Couchman JR, Kapoor R, Sthanam M, Wu RR. Source: The Journal of Biological Chemistry. 1996 April 19; 271(16): 9595-602. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=8621634&dopt=Abstract
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Plasma antibodies from malaria-exposed pregnant women recognize variant surface antigens on Plasmodium falciparum-infected erythrocytes in a parity-dependent manner and block parasite adhesion to chondroitin sulfate A. Author(s): Ricke CH, Staalsoe T, Koram K, Akanmori BD, Riley EM, Theander TG, Hviid L. Source: Journal of Immunology (Baltimore, Md. : 1950). 2000 September 15; 165(6): 330916. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10975848&dopt=Abstract
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Plasmodium falciparum cytoadherence to human placenta: evaluation of hyaluronic acid and chondroitin 4-sulfate for binding of infected erythrocytes. Author(s): Valiyaveettil M, Achur RN, Alkhalil A, Ockenhouse CF, Gowda DC. Source: Experimental Parasitology. 2001 October; 99(2): 57-65. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11748958&dopt=Abstract
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Plasmodium falciparum domain mediating adhesion to chondroitin sulfate A: a receptor for human placental infection. Author(s): Buffet PA, Gamain B, Scheidig C, Baruch D, Smith JD, Hernandez-Rivas R, Pouvelle B, Oishi S, Fujii N, Fusai T, Parzy D, Miller LH, Gysin J, Scherf A. Source: Proceedings of the National Academy of Sciences of the United States of America. 1999 October 26; 96(22): 12743-8. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10535993&dopt=Abstract
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Preferential binding of polyethylene glycol-coated liposomes containing a novel cationic lipid, TRX-20, to human subendthelial cells via chondroitin sulfate. Author(s): Harigai T, Kondo M, Isozaki M, Kasukawa H, Hagiwara H, Uchiyama H, Kimura J. Source: Pharmaceutical Research. 2001 September; 18(9): 1284-90. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11683241&dopt=Abstract
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Preparation and characterization of porous crosslinked collagenous matrices containing bioavailable chondroitin sulphate. Author(s): Pieper JS, Oosterhof A, Dijkstra PJ, Veerkamp JH, van Kuppevelt TH. Source: Biomaterials. 1999 May; 20(9): 847-58. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10226711&dopt=Abstract
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Presence of a laminin-binding chondroitin sulfate proteoglycan at the cell surface of a human melanoma cell Mel-85. Author(s): Elias MC, Veiga SS, Gremski W, Porcionatto MA, Nader HB, Brentani RR. Source: Molecular and Cellular Biochemistry. 1999 July; 197(1-2): 39-48. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10485322&dopt=Abstract
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Production of hyaluronan and chondroitin sulphate proteoglycans from human arterial smooth muscle--the effect of glucose, insulin, IGF-I or growth hormone. Author(s): Erikstrup C, Pedersen LM, Heickendorff L, Ledet T, Rasmussen LM. Source: European Journal of Endocrinology / European Federation of Endocrine Societies. 2001 August; 145(2): 193-8. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11454516&dopt=Abstract
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Purification and characterization of novel chondroitin ABC and AC lyases from Bacteroides stercoris HJ-15, a human intestinal anaerobic bacterium. Author(s): Hong SW, Kim BT, Shin HY, Kim WS, Lee KS, Kim YS, Kim DH. Source: European Journal of Biochemistry / Febs. 2002 June; 269(12): 2934-40. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12071957&dopt=Abstract
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Quantitative analysis on the localization of chondroitin sulfate proteoglycan in renal tissues of patients with calcium nephrolithiasis. Author(s): Chan VS, Li MK. Source: Urological Research. 1998; 26(4): 271-4. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=9760001&dopt=Abstract
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Quantitative computer image analysis of chondroitin sulfate A expression in placentas infected with Plasmodium falciparum. Author(s): Sartelet H, Garraud O, Lorenzato M, Rogier C, Milko-Sartelet I, Huerre M, Gaillard D. Source: The Journal of Histochemistry and Cytochemistry : Official Journal of the Histochemistry Society. 1999 June; 47(6): 751-6. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10330451&dopt=Abstract
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Recombinant human thrombomodulin(csa+): a tool for analyzing Plasmodium falciparum adhesion to chondroitin-4-sulfate. Author(s): Parzy D, Fusai T, Pouvelle B, Torrentino M, Eustacchio F, Lepolard C, Scherf A, Gysin J. Source: Microbes and Infection / Institut Pasteur. 2000 June; 2(7): 779-88. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10955958&dopt=Abstract
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Recovery of adhesion to chondroitin-4-sulphate in Plasmodium falciparum varCSA disruption mutants by antigenically similar PfEMP1 variants. Author(s): Andrews KT, Pirrit LA, Przyborski JM, Sanchez CP, Sterkers Y, Ricken S, Wickert H, Lepolard C, Avril M, Scherf A, Gysin J, Lanzer M. Source: Molecular Microbiology. 2003 August; 49(3): 655-69. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12864850&dopt=Abstract
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Regulated expression of chondroitin sulfates at sites of epithelial-mesenchymal interaction: spatio-temporal patterning identified with anti-chondroitin sulfate monoclonal antibodies. Author(s): Sorreli JM, Carrino DA, Caplan AI. Source: International Journal of Developmental Neuroscience : the Official Journal of the International Society for Developmental Neuroscience. 1996 June; 14(3): 233-48. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=8842801&dopt=Abstract
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Relative increase of biglycan and decorin and altered chondroitin sulfate epitopes in the degenerating human intervertebral disc. Author(s): Inkinen RI, Lammi MJ, Lehmonen S, Puustjarvi K, Kaapa E, Tammi MI. Source: The Journal of Rheumatology. 1998 March; 25(3): 506-14. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=9517772&dopt=Abstract
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Requirement of chondroitin sulfate/dermatan sulfate recognition in midkinedependent migration of macrophages. Author(s): Hayashi K, Kadomatsu K, Muramatsu T. Source: Glycoconjugate Journal. 2001 May; 18(5): 401-6. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11925507&dopt=Abstract
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Retroviral gene transfer is inhibited by chondroitin sulfate proteoglycans/glycosaminoglycans in malignant pleural effusions. Author(s): Batra RK, Olsen JC, Hoganson DK, Caterson B, Boucher RC. Source: The Journal of Biological Chemistry. 1997 May 2; 272(18): 11736-43. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=9115227&dopt=Abstract
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Role of chondroitin 4-sulphate as a receptor for polycation induced human platelet aggregation. Author(s): Donato JL, Marcondes S, Antunes E, Nogueira MD, Nader HB, Dietrich CP, Rendu F, de Nucci G. Source: British Journal of Pharmacology. 1996 December; 119(7): 1447-53. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=8968554&dopt=Abstract
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Roles of aggrecan, a large chondroitin sulfate proteoglycan, in cartilage structure and function. Author(s): Watanabe H, Yamada Y, Kimata K. Source: Journal of Biochemistry. 1998 October; 124(4): 687-93. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=9756610&dopt=Abstract
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Secreted chondroitin sulfate proteoglycan of human B cell lines binds to the complement protein C1q and inhibits complex formation of C1. Author(s): Kirschfink M, Blase L, Engelmann S, Schwartz-Albiez R. Source: Journal of Immunology (Baltimore, Md. : 1950). 1997 February 1; 158(3): 1324-31. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=9013976&dopt=Abstract
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Semisynthetic chondroitins as chiral buffer additives in capillary electrophoresis. Author(s): Gotti R, Cavrini V, Andrisano V, Mascellani G. Source: J Chromatogr A. 1999 June 11; 845(1-2): 247-56. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10399339&dopt=Abstract
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Sequestration of Plasmodium falciparum-infected erythrocytes to chondroitin sulfate A, a receptor for maternal malaria: monoclonal antibodies against the native parasite ligand reveal pan-reactive epitopes in placental isolates. Author(s): Lekana Douki JB, Traore B, Costa FT, Fusai T, Pouvelle B, Sterkers Y, Scherf A, Gysin J. Source: Blood. 2002 August 15; 100(4): 1478-83. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12149234&dopt=Abstract
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Serum and synovial fluid levels of chondroitin sulfate in patients with osteoarthritis of the knee joint. Author(s): Uesaka S, Nakayama Y, Shirai Y, Yoshihara K. Source: Journal of Nippon Medical School = Nihon Ika Daigaku Zasshi. 2001 April; 68(2): 165-70. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11301362&dopt=Abstract
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Significance of chondroitin sulfate isomers in the synovial fluid of osteoarthritis patients. Author(s): Uesaka S, Nakayama Y, Yoshihara K, Ito H. Source: Journal of Orthopaedic Science : Official Journal of the Japanese Orthopaedic Association. 2002; 7(2): 232-7. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11956984&dopt=Abstract
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Simple approach to predict the maximal effect elicited by a drug when plasma concentrations are not available or are dissociated from the effect, as illustrated with chondroitin sulfate data. Author(s): du Souich P, Verges J. Source: Clinical Pharmacology and Therapeutics. 2001 July; 70(1): 5-9. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11452238&dopt=Abstract
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Specific molecular interactions of oversulfated chondroitin sulfate E with various heparin-binding growth factors. Implications as a physiological binding partner in the brain and other tissues. Author(s): Deepa SS, Umehara Y, Higashiyama S, Itoh N, Sugahara K. Source: The Journal of Biological Chemistry. 2002 November 15; 277(46): 43707-16. Epub 2002 September 06. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12221095&dopt=Abstract
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Stem cell factor-dependent human cord blood derived mast cells express alpha- and beta-tryptase, heparin and chondroitin sulphate. Author(s): Nilsson G, Blom T, Harvima I, Kusche-Gullberg M, Nilsson K, Hellman L. Source: Immunology. 1996 June; 88(2): 308-14. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=8690466&dopt=Abstract
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Steroid-responsive myopathy with deficient chondroitin sulfate C in skeletal muscle connective tissue. Author(s): al-Lozi MT, Hemelt VB, Pestronk A. Source: Neurology. 1998 February; 50(2): 526-9. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=9484390&dopt=Abstract
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Storage of human corneas in dextran and chondroitin sulfate-based corneal storage medium: changes in stromal free sodium. Author(s): Jablonski-Stiemke MM, Edelhauser HF. Source: Archives of Ophthalmology. 1998 May; 116(5): 627-32. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=9596499&dopt=Abstract
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Structural and symptomatic efficacy of glucosamine and chondroitin in knee osteoarthritis: a comprehensive meta-analysis. Author(s): Richy F, Bruyere O, Ethgen O, Cucherat M, Henrotin Y, Reginster JY. Source: Archives of Internal Medicine. 2003 July 14; 163(13): 1514-22. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12860572&dopt=Abstract
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Structural requirements for the adherence of Plasmodium falciparum-infected erythrocytes to chondroitin sulfate proteoglycans of human placenta. Author(s): Alkhalil A, Achur RN, Valiyaveettil M, Ockenhouse CF, Gowda DC. Source: The Journal of Biological Chemistry. 2000 December 22; 275(51): 40357-64. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11005815&dopt=Abstract
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Structure and anticoagulant activity of a fucosylated chondroitin sulfate from echinoderm. Sulfated fucose branches on the polysaccharide account for its high anticoagulant action. Author(s): Mourao PA, Pereira MS, Pavao MS, Mulloy B, Tollefsen DM, Mowinckel MC, Abildgaard U. Source: The Journal of Biological Chemistry. 1996 September 27; 271(39): 23973-84. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=8798631&dopt=Abstract
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Sulfated polysaccharides (chondroitin sulfate and carrageenan) plus glucosamine sulfate are potent inhibitors of HIV. Author(s): Konlee M. Source: Posit Health News. 1998 Fall; (No 17): 4-7. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11366556&dopt=Abstract
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Sulfation of chondroitin sulfate in human articular cartilage. The effect of age, topographical position, and zone of cartilage on tissue composition. Author(s): Bayliss MT, Osborne D, Woodhouse S, Davidson C. Source: The Journal of Biological Chemistry. 1999 May 28; 274(22): 15892-900. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10336494&dopt=Abstract
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Sulfation of chondroitin/dermatan sulfate by cystic fibrosis pancreatic duct cells is not different from control cells. Author(s): Hill WG, Harper GS, Rozaklis T, Hopwood JJ. Source: Biochemical and Molecular Medicine. 1997 October; 62(1): 85-94. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=9367803&dopt=Abstract
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Sulphation heterogeneity in the trisaccharide (GalNAcSbeta1, 4GlcAbeta1,3GalNAcS) isolated from the non-reducing terminal of human aggrecan chondroitin sulphate. Author(s): West LA, Roughley P, Nelson FR, Plaas AH. Source: The Biochemical Journal. 1999 August 15; 342 ( Pt 1): 223-9. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10432320&dopt=Abstract
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Surface modification of diaspirin cross-linked hemoglobin (DCLHb) with chondroitin-4-sulfate derivatives. Part 1. Author(s): Hai TT, Pereira DE, Nelson DJ, Catarello J, Srnak A. Source: Bioconjugate Chemistry. 2000 September-October; 11(5): 705-13. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10995215&dopt=Abstract
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Synovial fluid chondroitin and keratan sulphate epitopes, glycosaminoglycans, and hyaluronan in arthritic and normal knees. Author(s): Belcher C, Yaqub R, Fawthrop F, Bayliss M, Doherty M. Source: Annals of the Rheumatic Diseases. 1997 May; 56(5): 299-307. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=9175930&dopt=Abstract
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Synovial fluid chondroitin sulphate epitopes 3B3 and 7D4, and glycosaminoglycan in human knee osteoarthritis after exercise. Author(s): Bautch JC, Clayton MK, Chu Q, Johnson KA. Source: Annals of the Rheumatic Diseases. 2000 November; 59(11): 887-91. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11053067&dopt=Abstract
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The adhesion of Plasmodium falciparum-infected erythrocytes to chondroitin sulfate A is mediated by P. falciparum erythrocyte membrane protein 1. Author(s): Reeder JC, Cowman AF, Davern KM, Beeson JG, Thompson JK, Rogerson SJ, Brown GV. Source: Proceedings of the National Academy of Sciences of the United States of America. 1999 April 27; 96(9): 5198-202. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10220443&dopt=Abstract
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The apolipoprotein E-dependent low density lipoprotein cholesteryl ester selective uptake pathway in murine adrenocortical cells involves chondroitin sulfate proteoglycans and an alpha 2-macroglobulin receptor. Author(s): Swarnakar S, Beers J, Strickland DK, Azhar S, Williams DL. Source: The Journal of Biological Chemistry. 2001 June 15; 276(24): 21121-8. Epub 2001 March 26. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11274190&dopt=Abstract
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The chondroitin sulfate chain of bikunin-containing proteins in the inter-alphainhibitor family increases in size in inflammatory diseases. Author(s): Mizon C, Mairie C, Balduyck M, Hachulla E, Mizon J. Source: European Journal of Biochemistry / Febs. 2001 May; 268(9): 2717-24. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11322893&dopt=Abstract
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The cysteine-rich domain of the macrophage mannose receptor is a multispecific lectin that recognizes chondroitin sulfates A and B and sulfated oligosaccharides of blood group Lewis(a) and Lewis(x) types in addition to the sulfated N-glycans of lutropin. Author(s): Leteux C, Chai W, Loveless RW, Yuen CT, Uhlin-Hansen L, Combarnous Y, Jankovic M, Maric SC, Misulovin Z, Nussenzweig MC, Feizi T. Source: The Journal of Experimental Medicine. 2000 April 3; 191(7): 1117-26. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10748230&dopt=Abstract
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The effect of glucosamine-chondroitin supplementation on glycosylated hemoglobin levels in patients with type 2 diabetes mellitus: a placebo-controlled, double-blinded, randomized clinical trial. Author(s): Scroggie DA, Albright A, Harris MD. Source: Archives of Internal Medicine. 2003 July 14; 163(13): 1587-90. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12860582&dopt=Abstract
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The effects of age and sex on chondroitin sulfates in normal synovial fluid. Author(s): Nakayama Y, Narita T, Mori A, Uesaka S, Miyazaki K, Ito H. Source: Arthritis and Rheumatism. 2002 August; 46(8): 2105-8. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12209515&dopt=Abstract
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The effects of glucosamine and chondroitin sulfate on osteoarthritis of the TMJ: a preliminary report of 50 patients. Author(s): Shankland WE 2nd. Source: Cranio. 1998 October; 16(4): 230-5. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10029750&dopt=Abstract
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The effects of low density lipoproteins modified by incubation with chondroitin 6sulfate on human aortic smooth muscle cells. Author(s): Tirziu D, Jinga VV, Serban G, Simionescu M. Source: Atherosclerosis. 1999 November 1; 147(1): 155-66. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10525137&dopt=Abstract
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The efficacy of chondroitin sulfate 0.2% in treating interstitial cystitis. Author(s): Steinhoff G, Ittah B, Rowan S. Source: Can J Urol. 2002 February; 9(1): 1454-8. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11886599&dopt=Abstract
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The folded protein modules of the C-terminal G3 domain of aggrecan can each facilitate the translocation and secretion of the extended chondroitin sulfate attachment sequence. Author(s): Day JM, Murdoch AD, Hardingham TE. Source: The Journal of Biological Chemistry. 1999 December 31; 274(53): 38107-11. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10608880&dopt=Abstract
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The low sulfated chondroitin sulfate proteoglycans of human placenta have sulfate group-clustered domains that can efficiently bind Plasmodium falciparum-infected erythrocytes. Author(s): Achur RN, Valiyaveettil M, Gowda DC. Source: The Journal of Biological Chemistry. 2003 March 28; 278(13): 11705-13. Epub 2003 January 06. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12517756&dopt=Abstract
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The NG2 chondroitin sulfate proteoglycan: role in malignant progression of human brain tumours. Author(s): Chekenya M, Rooprai HK, Davies D, Levine JM, Butt AM, Pilkington GJ. Source: International Journal of Developmental Neuroscience : the Official Journal of the International Society for Developmental Neuroscience. 1999 August-October; 17(5-6): 421-35. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10571405&dopt=Abstract
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The osmotic pressure of chondroitin sulphate solutions: experimental measurements and theoretical analysis. Author(s): Ehrlich S, Wolff N, Schneiderman R, Maroudas A, Parker KH, Winlove CP. Source: Biorheology. 1998 November-December; 35(6): 383-97. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10656048&dopt=Abstract
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The relevance of chondroitin and keratan sulphate markers in normal and arthritic synovial fluid. Author(s): Sharif M, Osborne DJ, Meadows K, Woodhouse SM, Colvin EM, Shepstone L, Dieppe PA. Source: British Journal of Rheumatology. 1996 October; 35(10): 951-7. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=8883432&dopt=Abstract
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The role of chondroitin sulfate chains of urinary trypsin inhibitor in inhibition of LPS-induced increase of cytosolic free Ca2+ in HL60 cells and HUVEC cells. Author(s): Kanayama N, Maehara K, Suzuki M, Fujise Y, Terao T. Source: Biochemical and Biophysical Research Communications. 1997 September 18; 238(2): 560-4. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=9299551&dopt=Abstract
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The role of glucosamine sulfate and chondroitin sulfates in the treatment of degenerative joint disease. Author(s): Kelly GS. Source: Alternative Medicine Review : a Journal of Clinical Therapeutic. 1998 February; 3(1): 27-39. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=9600024&dopt=Abstract
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The sulfation pattern of chondroitin sulfate from articular cartilage explants in response to mechanical loading. Author(s): Sauerland K, Plaas AH, Raiss RX, Steinmeyer J. Source: Biochimica Et Biophysica Acta. 2003 July 30; 1638(3): 241-8. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12878325&dopt=Abstract
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Transcription of multiple var genes by individual, trophozoite-stage Plasmodium falciparum cells expressing a chondroitin sulphate A binding phenotype. Author(s): Duffy MF, Brown GV, Basuki W, Krejany EO, Noviyanti R, Cowman AF, Reeder JC. Source: Molecular Microbiology. 2002 March; 43(5): 1285-93. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11918813&dopt=Abstract
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Two distinct chondroitin sulfate ABC lyases. An endoeliminase yielding tetrasaccharides and an exoeliminase preferentially acting on oligosaccharides. Author(s): Hamai A, Hashimoto N, Mochizuki H, Kato F, Makiguchi Y, Horie K, Suzuki S. Source: The Journal of Biological Chemistry. 1997 April 4; 272(14): 9123-30. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=9083041&dopt=Abstract
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Ultrasensitive capillary electrophoresis of sulfated disaccharides in chondroitin/dermatan sulfates by laser-induced fluorescence after derivatization with 2-aminoacridone. Author(s): Lamari F, Theocharis A, Hjerpe A, Karamanos NK. Source: J Chromatogr B Biomed Sci Appl. 1999 June 25; 730(1): 129-33. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10437680&dopt=Abstract
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Urinary chondroitin sulfates, heparan sulfate and total sulfated glycosaminoglycans in interstitial cystitis. Author(s): Erickson DR, Ordille S, Martin A, Bhavanandan VP. Source: The Journal of Urology. 1997 January; 157(1): 61-4. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=8976216&dopt=Abstract
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Use of a resorbable hydroxyapatite-collagen chondroitin sulfate material on immediate postextraction sites: a clinical and histologic study. Author(s): Rebaudi A, Silvestrini P, Trisi P. Source: Int J Periodontics Restorative Dent. 2003 August; 23(4): 371-9. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12956481&dopt=Abstract
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Use of glucosamine and chondroitin sulfate in the management of osteoarthritis. Author(s): Arnold EL, Arnold WJ. Source: J Am Acad Orthop Surg. 2001 September-October; 9(5): 352-3. No Abstract Available. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11599524&dopt=Abstract
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Use of glucosamine and chondroitin sulfate in the management of osteoarthritis. Author(s): Brief AA, Maurer SG, Di Cesare PE. Source: J Am Acad Orthop Surg. 2001 March-April; 9(2): 71-8. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11281631&dopt=Abstract
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Variants of Plasmodium falciparum erythrocyte membrane protein 1 expressed by different placental parasites are closely related and adhere to chondroitin sulfate A. Author(s): Khattab A, Kun J, Deloron P, Kremsner PG, Klinkert MQ. Source: The Journal of Infectious Diseases. 2001 April 1; 183(7): 1165-9. Epub 2001 February 28. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11237850&dopt=Abstract
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Variations in the chondroitin sulfate-protein linkage region of aggrecans from bovine nasal and human articular cartilages. Author(s): Cheng F, Heinegard D, Fransson L, Bayliss M, Bielicki J, Hopwood J, Yoshida K. Source: The Journal of Biological Chemistry. 1996 November 8; 271(45): 28572-80. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=8910487&dopt=Abstract
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White matter extracellular matrix chondroitin sulfate/dermatan sulfate proteoglycans in multiple sclerosis. Author(s): Sobel RA, Ahmed AS. Source: Journal of Neuropathology and Experimental Neurology. 2001 December; 60(12): 1198-207. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11764092&dopt=Abstract
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CHAPTER 2. NUTRITION AND CHONDROITIN Overview In this chapter, we will show you how to find studies dedicated specifically to nutrition and chondroitin.
Finding Nutrition Studies on Chondroitin 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 “chondroitin” (or synonyms) into the search box, and click “Go.” To narrow the search, you can also select the “Title” field.
7
Adapted from http://ods.od.nih.gov. IBIDS is produced by the Office of Dietary Supplements (ODS) at the National Institutes of Health to assist the public, healthcare providers, educators, and researchers in locating credible, scientific information on dietary supplements. IBIDS was developed and will be maintained through an interagency partnership with the Food and Nutrition Information Center of the National Agricultural Library, U.S. Department of Agriculture.
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The following is a typical result when searching for recently indexed consumer information on chondroitin: •
A friend recommended I take a dietary supplement for my arthritis that contains glucosamine and chondroitin. What are these made from? Do they help? Source: Anonymous Mayo-Clin-Health-Lett. 2003 January; 21(1): 8 0741-6245
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A look at glucosamine and chondroitin for easing arthritis pain. Source: Tufts-Univ-health-nutr-lett. New York, NY : Tufts University Health & Nutrition Letter, c1997-. January 2000. volume 17 (11) page 4-5.
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A novel repeat in the melanoma-associated chondroitin sulfate proteoglycan defines a new protein family. Author(s): metaGen Pharmaceuticals GmbH, Oudenarder Str. 16, D-13347, Berlin, Germany.
[email protected] Source: Staub, E Hinzmann, B Rosenthal, A FEBS-Lett. 2002 September 11; 527(1-3): 1148 0014-5793
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A sensitive assay for the measurement of serum chondroitin sulfate 3B3(-) epitope levels in human rheumatic diseases. Author(s): Department of Medicine, University of Western Australia, Division of Clinical Pathology, Western Australian Centre for Pathology and Medical Research (PathCentre), Nedlands. Source: Chan, S S Kent, G N Will, R K Clin-Exp-Rheumatol. 2001 Sep-October; 19(5): 533-40 0392-856X
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Aggregation of LDL with chondroitin-4-sulfate makes LDL oxidizable in the presence of water-soluble antioxidants. Author(s): Institute of Molecular Biology, Biochemistry and Microbiology, SFB Biomembrane Research Center, University of Graz, Schubertstrasse 1, A-8010, Graz, Austria.
[email protected] Source: Abuja, Peter M FEBS-Lett. 2002 Feb 13; 512(1-3): 245-8 0014-5793
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Arterial wall chondroitin sulfate proteoglycans: diverse molecules with distinct roles in lipoprotein retention and atherogenesis. Author(s): Dorrance H. Hamilton Research Laboratories, Division of Endocrinology, Diabetes & Metabolic Diseases, Department of Medicine, Jefferson Medical College, Thomas Jefferson University, Philadelphia, Pennsylvania 19107, USA.
[email protected] Source: Williams, K J Curr-Opin-Lipidol. 2001 October; 12(5): 477-87 0957-9672
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Binding characteristics of chondroitin sulfate proteoglycans and laminin-1, and correlative neurite outgrowth behaviors in a standard tissue culture choice assay. Author(s): University of Kentucky, Department of Anatomy and Neurobiology, Chandler Medical Center, Lexington 40536-0298, USA.
[email protected] Source: Snow, D M Smith, J D Gurwell, J A J-Neurobiol. 2002 June 15; 51(4): 285-301 0022-3034
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Biochemical properties of a keratan sulphate/chondroitin sulphate proteoglycan expressed in primate pluripotent stem cells. Author(s): University College London, UK. Source: Cooper, Susan Bennett, William Andrade, Jessica Reubinoff, Benjamin E Thomson, James Pera, Martin F J-Anat. 2002 Mar; 200(Pt 3): 259-65 0021-8782
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Chondroitin sulfate A released from platelets blocks RANTES presentation on cell surfaces and RANTES-dependent firm adhesion of leukocytes. Author(s): Medical Policlinic, University of Munich, Munich, Germany.
[email protected] Source: Mack, Matthias Pfirstinger, Jochen Weber, Christian Weber, Kim S C Nelson, Peter J Rupp, Tamara Maletz, Konstantin Bruhl, Hilke Schlondorff, Detlef Eur-JImmunol. 2002 April; 32(4): 1012-20 0014-2980
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Chondroitin sulfate disrupts axon pathfinding in the optic tract and alters growth cone dynamics. Author(s): University of California San Diego, Department of Biology, La Jolla, CA 92093, USA. Source: Walz, A Anderson, R B Irie, A Chien, C B Holt, C E J-Neurobiol. 2002 November 15; 53(3): 330-42 0022-3034
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Chondroitin sulfate proteoglycan at the basal lamina beneath high endothelial cells in human palatine tonsils: a light and electron microscopic study using the cationic colloidal iron method. Author(s): Section of Otolaryngology-Head and Neck Surgery, Graduate School of Medicine and Dentistry, Faculty of Health Sciences, Okayama University, Japan.
[email protected] Source: Sunami Kataoka, Y Akagi, H Nishizaki, K Taguchi, T Murakami, T Ohtsuka, A Arch-Histol-Cytol. 2001 December; 64(5): 535-43 0914-9465
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Chondroitin sulfate-coated polyhydroxyethyl methacrylate membrane prevents adhesion in full-thickness tendon tears of rabbits. Author(s): Department of Orthopaedic Surgery and Traumatology, Kirikkale University School of Medicine, Kirikkale, Turkey. Source: Gudemez, E Eksioglu, F Korkusuz, P Asan, E Gursel, I Hasirci, V J-Hand-Surg[Am]. 2002 March; 27(2): 293-306 0363-5023
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Chondroitin sulphate proteoglycans in the CNS injury response. Author(s): Physiological Laboratory, Centre for Brain Repair, Cambridge University, E.D. Adrian Building, Forvie Site, Robinson Way, Cambridge CB2 2PY, UK. Source: Morgenstern, D A Asher, R A Fawcett, J W Prog-Brain-Res. 2002; 137: 313-32 0079-6123
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Chondroitin sulphate proteoglycans: inhibitory components of the glial scar. Author(s): Physiological Laboratory, University of Cambridge, Downing Street, CB2 3EG Cambridge, UK.
[email protected] Source: Asher, R A Morgenstern, D A Moon, L D Fawcett, J W Prog-Brain-Res. 2001; 132: 611-9 0079-6123
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Degradation of chondroitin sulfate and dermatan sulfate with chondroitin lyases. Author(s): Division of Medicinal and Natural Products Chemistry, Department of Chemistry, University of Iowa, Iowa City, IA, USA. Source: Hernaiz, M J Linhardt, R J Methods-Mol-Biol. 2001; 171: 363-71 1064-3745
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Disaccharide composition of hyaluronan and chondroitin/dermatan sulfate. Analysis with fluorophore-assisted carbohydrate electrophoresis. Author(s): Center for Research in Skeletal Development and Pediatric Orthopedics, Shriners Hospital for Children, Tampa, FL, USA. Source: Plaas, A H West, L Midura, R J Hascall, V C Methods-Mol-Biol. 2001; 171: 117-28 1064-3745
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Effect of chondroitin sulfate on the biodegradation and drug release of chitosan gel beads in subcutaneous air pouches of mice. Author(s): Faculty of Pharmaceutical Sciences, Hokuriku University, Kanazawa, Japan.
[email protected] Source: Kofuji, Kyoko Ito, Tomohiro Murata, Yoshifumi Kawashima, Susumu BiolPharm-Bull. 2002 February; 25(2): 268-71 0918-6158
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Glucosamine & chondroitin: joint relief. Source: Schardt, D. Nutr-action-health-lett. [Washington, D.C. : Center for Science in the Public Interest,. October 2000. volume 27 (8) page 10. 0885-7792
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Herpes simplex virus type 1 glycoprotein C is necessary for efficient infection of chondroitin sulfate-expressing gro2C cells. Author(s): Department of Clinical Virology, Goteborg University, Guldhedsgatan 10B, S-413 46 Goteborg, Sweden.
[email protected] Source: Mardberg, Kristina Trybala, Edward Tufaro, Frank Bergstrom, Tomas J-GenVirol. 2002 February; 83(Pt 2): 291-300 0022-1317
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Immunohistochemical localization of large chondroitin sulfate proteoglycan in odontogenic tumor. Author(s): Department of Oral Pathology, Kanagawa Dental College, Yokosuka, Japan. Source: Ito, Y Abiko, Y Tanaka, Y Rahemtulla, F Kaku, T Med-Electron-Microsc. 2002 September; 35(3): 173-7 0918-4287
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Immunohistochemical localization of large chondroitin sulphate proteoglycan in porcine gingival epithelia. Author(s): Department of Oral Pathology, School of Dentistry, Health Sciences University of Hokkaido, Japan.
[email protected] Source: Abiko, Y Nishimura, M Rahemtulla, F Mizoguchi, I Kaku, T Eur-J-Morphol. 2001 April; 39(2): 99-104 0924-3860
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Inhibition of articular cartilage degradation by glucosamine-HCl and chondroitin sulphate. Author(s): Department of Animal Science, Michigan State University, East Lansing 48824-1225, USA. Source: Orth, M W Peters, T L Hawkins, J N Equine-Vet-J-Suppl. 2002 September; (34): 224-9
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NG2 is a major chondroitin sulfate proteoglycan produced after spinal cord injury and is expressed by macrophages and oligodendrocyte progenitors. Author(s): Department of Neurosciences, University of California, San Diego, La Jolla, California 92093, USA. Source: Jones, Leonard L Yamaguchi, Yu Stallcup, William B Tuszynski, Mark H JNeurosci. 2002 April 1; 22(7): 2792-803 1529-2401
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Purification and characterization of novel chondroitin ABC and AC lyases from Bacteroides stercoris HJ-15, a human intestinal anaerobic bacterium. Author(s): College of Pharmacy, Kyung Hee University, Seoul, Korea. Source: Hong, Sung Woon Kim, Byung Taek Shin, Ho Young Kim, Wan Suk Lee, Keun Sook Kim, Yeong Shik Kim, Dong Hyun Eur-J-Biochem. 2002 June; 269(12): 2934-40 0014-2956
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Repellent guidance of regenerating optic axons by chondroitin sulfate glycosaminoglycans in zebrafish. Author(s): Zentrum fur Molekulare Neurobiologie Hamburg, Universitat Hamburg, D20246 Hamburg, Germany.
[email protected]
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Source: Becker, Catherina G Becker, Thomas J-Neurosci. 2002 February 1; 22(3): 842-53 1529-2401 •
Significance of chondroitin sulfate isomers in the synovial fluid of osteoarthritis patients. Author(s): Department of Orthopaedic Surgery, Nippon Medical School, 1-1-5 Sendagi, Bunkyo-ku, Tokyo 113-8602, Japan. Source: Uesaka, Shinji Nakayama, Yoshihito Yoshihara, Kiyoshi Ito, Hiromoto J-OrthopSci. 2002; 7(2): 232-7 0949-2658
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Stability of a cisplatin-chondroitin sulfate A complex in plasma and kidney in terms of protein binding. Author(s): Faculty of Pharmaceutical Science, Kumamoto University, Japan. Source: Zhang, J S Shen Feng, M A Suenaga, A Otagiri, M Biol-Pharm-Bull. 2001 August; 24(8): 970-2 0918-6158
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TGF-beta(3)-induced chondroitin sulphate proteoglycan mediates palatal shelf adhesion. Author(s): Departamento de Anatomia Humana, Facultad de Medicina, Universidad de Valladolid, Valladolid 47005, Spain. Source: Gato, A Martinez, M L Tudela, C Alonso, I Moro, J A Formoso, M A Ferguson, M W Martinez Alvarez, C Dev-Biol. 2002 October 15; 250(2): 393-405 0012-1606
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The bioavailability and pharmacokinetics of glucosamine hydrochloride and low molecular weight chondroitin sulfate after single and multiple doses to beagle dogs. Author(s): Center for Drug Evaluation and Research, Food and Drug Administration, Rockville, MD, USA. Source: Adebowale, A Du, J Liang, Z Leslie, J L Eddington, N D Biopharm-Drug-Dispos. 2002 September; 23(6): 217-25 0142-2782
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The efficacy of chondroitin sulfate 0.2% in treating interstitial cystitis. Author(s): Department of Urology, Capital Health Region, Victoria, BC, Canada. Source: Steinhoff, G Ittah, B Rowan, S Can-J-Urol. 2002 February; 9(1): 1454-8 1195-9479
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The intensely positively charged perineuronal net in the adult rat brain, with special reference to its reactions to oxine, chondroitinase ABC, hyaluronidase and collagenase. Author(s): Section of Human Morphology, Biophysiological Science, Graduate School of Medicine and Dentistry, Okayama University, Japan.
[email protected] Source: Murakami, T Kosaka, M Sato, H Ohtsuka, A Taguchi, T Arch-Histol-Cytol. 2001 August; 64(3): 313-8 0914-9465
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Transcription of multiple var genes by individual, trophozoite-stage Plasmodium falciparum cells expressing a chondroitin sulphate A binding phenotype. Author(s): Australian Indonesia Medical Research Initiative (AusAID), Eijkman Institute for Molecular Biology, Eijkman Building, Jl. Diponegoro 69, Jakarta, Indonesia 10430.
[email protected] Source: Duffy, Michael F Brown, Graham V Basuki, Wanny Krejany, Efrosinia O Noviyanti, Rintis Cowman, Alan F Reeder, John C Mol-Microbiol. 2002 March; 43(5): 1285-93 0950-382X
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White matter extracellular matrix chondroitin sulfate/dermatan sulfate proteoglycans in multiple sclerosis. Author(s): Department of Pathology, Stanford University School of Medicine, California 94305, USA.
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Source: Sobel, R A Ahmed, A S J-Neuropathol-Exp-Neurol. 2001 December; 60(12): 1198207 0022-3069 The following information is typical of that found when using the “Full IBIDS Database” to search for “chondroitin” (or a synonym): •
A friend recommended I take a dietary supplement for my arthritis that contains glucosamine and chondroitin. What are these made from? Do they help? Source: Anonymous Mayo-Clin-Health-Lett. 2003 January; 21(1): 8 0741-6245
•
A look at glucosamine and chondroitin for easing arthritis pain. Source: Tufts-Univ-health-nutr-lett. New York, NY : Tufts University Health & Nutrition Letter, c1997-. January 2000. volume 17 (11) page 4-5.
•
A novel repeat in the melanoma-associated chondroitin sulfate proteoglycan defines a new protein family. Author(s): metaGen Pharmaceuticals GmbH, Oudenarder Str. 16, D-13347, Berlin, Germany.
[email protected] Source: Staub, E Hinzmann, B Rosenthal, A FEBS-Lett. 2002 September 11; 527(1-3): 1148 0014-5793
•
A sensitive assay for the measurement of serum chondroitin sulfate 3B3(-) epitope levels in human rheumatic diseases. Author(s): Department of Medicine, University of Western Australia, Division of Clinical Pathology, Western Australian Centre for Pathology and Medical Research (PathCentre), Nedlands. Source: Chan, S S Kent, G N Will, R K Clin-Exp-Rheumatol. 2001 Sep-October; 19(5): 533-40 0392-856X
•
Aggregation of LDL with chondroitin-4-sulfate makes LDL oxidizable in the presence of water-soluble antioxidants. Author(s): Institute of Molecular Biology, Biochemistry and Microbiology, SFB Biomembrane Research Center, University of Graz, Schubertstrasse 1, A-8010, Graz, Austria.
[email protected] Source: Abuja, Peter M FEBS-Lett. 2002 Feb 13; 512(1-3): 245-8 0014-5793
•
Arterial wall chondroitin sulfate proteoglycans: diverse molecules with distinct roles in lipoprotein retention and atherogenesis. Author(s): Dorrance H. Hamilton Research Laboratories, Division of Endocrinology, Diabetes & Metabolic Diseases, Department of Medicine, Jefferson Medical College, Thomas Jefferson University, Philadelphia, Pennsylvania 19107, USA.
[email protected] Source: Williams, K J Curr-Opin-Lipidol. 2001 October; 12(5): 477-87 0957-9672
•
Binding characteristics of chondroitin sulfate proteoglycans and laminin-1, and correlative neurite outgrowth behaviors in a standard tissue culture choice assay. Author(s): University of Kentucky, Department of Anatomy and Neurobiology, Chandler Medical Center, Lexington 40536-0298, USA.
[email protected] Source: Snow, D M Smith, J D Gurwell, J A J-Neurobiol. 2002 June 15; 51(4): 285-301 0022-3034
•
Biochemical properties of a keratan sulphate/chondroitin sulphate proteoglycan expressed in primate pluripotent stem cells. Author(s): University College London, UK. Source: Cooper, Susan Bennett, William Andrade, Jessica Reubinoff, Benjamin E Thomson, James Pera, Martin F J-Anat. 2002 Mar; 200(Pt 3): 259-65 0021-8782
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•
Chondroitin sulfate A released from platelets blocks RANTES presentation on cell surfaces and RANTES-dependent firm adhesion of leukocytes. Author(s): Medical Policlinic, University of Munich, Munich, Germany.
[email protected] Source: Mack, Matthias Pfirstinger, Jochen Weber, Christian Weber, Kim S C Nelson, Peter J Rupp, Tamara Maletz, Konstantin Bruhl, Hilke Schlondorff, Detlef Eur-JImmunol. 2002 April; 32(4): 1012-20 0014-2980
•
Chondroitin sulfate-coated polyhydroxyethyl methacrylate membrane prevents adhesion in full-thickness tendon tears of rabbits. Author(s): Department of Orthopaedic Surgery and Traumatology, Kirikkale University School of Medicine, Kirikkale, Turkey. Source: Gudemez, E Eksioglu, F Korkusuz, P Asan, E Gursel, I Hasirci, V J-Hand-Surg[Am]. 2002 March; 27(2): 293-306 0363-5023
•
Chondroitin sulphate proteoglycans in the CNS injury response. Author(s): Physiological Laboratory, Centre for Brain Repair, Cambridge University, E.D. Adrian Building, Forvie Site, Robinson Way, Cambridge CB2 2PY, UK. Source: Morgenstern, D A Asher, R A Fawcett, J W Prog-Brain-Res. 2002; 137: 313-32 0079-6123
•
Degradation of chondroitin sulfate and dermatan sulfate with chondroitin lyases. Author(s): Division of Medicinal and Natural Products Chemistry, Department of Chemistry, University of Iowa, Iowa City, IA, USA. Source: Hernaiz, M J Linhardt, R J Methods-Mol-Biol. 2001; 171: 363-71 1064-3745
•
Disaccharide composition of hyaluronan and chondroitin/dermatan sulfate. Analysis with fluorophore-assisted carbohydrate electrophoresis. Author(s): Center for Research in Skeletal Development and Pediatric Orthopedics, Shriners Hospital for Children, Tampa, FL, USA. Source: Plaas, A H West, L Midura, R J Hascall, V C Methods-Mol-Biol. 2001; 171: 117-28 1064-3745
•
Effect of chondroitin sulfate on the biodegradation and drug release of chitosan gel beads in subcutaneous air pouches of mice. Author(s): Faculty of Pharmaceutical Sciences, Hokuriku University, Kanazawa, Japan.
[email protected] Source: Kofuji, Kyoko Ito, Tomohiro Murata, Yoshifumi Kawashima, Susumu BiolPharm-Bull. 2002 February; 25(2): 268-71 0918-6158
•
Glucosamine & chondroitin: joint relief. Source: Schardt, D. Nutr-action-health-lett. [Washington, D.C. : Center for Science in the Public Interest,. October 2000. volume 27 (8) page 10. 0885-7792
•
Herpes simplex virus type 1 glycoprotein C is necessary for efficient infection of chondroitin sulfate-expressing gro2C cells. Author(s): Department of Clinical Virology, Goteborg University, Guldhedsgatan 10B, S-413 46 Goteborg, Sweden.
[email protected] Source: Mardberg, Kristina Trybala, Edward Tufaro, Frank Bergstrom, Tomas J-GenVirol. 2002 February; 83(Pt 2): 291-300 0022-1317
•
Immunohistochemical localization of large chondroitin sulfate proteoglycan in odontogenic tumor. Author(s): Department of Oral Pathology, Kanagawa Dental College, Yokosuka, Japan. Source: Ito, Y Abiko, Y Tanaka, Y Rahemtulla, F Kaku, T Med-Electron-Microsc. 2002 September; 35(3): 173-7 0918-4287
118 Chondroitin
•
Inhibition of articular cartilage degradation by glucosamine-HCl and chondroitin sulphate. Author(s): Department of Animal Science, Michigan State University, East Lansing 48824-1225, USA. Source: Orth, M W Peters, T L Hawkins, J N Equine-Vet-J-Suppl. 2002 September; (34): 224-9
•
NG2 is a major chondroitin sulfate proteoglycan produced after spinal cord injury and is expressed by macrophages and oligodendrocyte progenitors. Author(s): Department of Neurosciences, University of California, San Diego, La Jolla, California 92093, USA. Source: Jones, Leonard L Yamaguchi, Yu Stallcup, William B Tuszynski, Mark H JNeurosci. 2002 April 1; 22(7): 2792-803 1529-2401
•
Purification and characterization of novel chondroitin ABC and AC lyases from Bacteroides stercoris HJ-15, a human intestinal anaerobic bacterium. Author(s): College of Pharmacy, Kyung Hee University, Seoul, Korea. Source: Hong, Sung Woon Kim, Byung Taek Shin, Ho Young Kim, Wan Suk Lee, Keun Sook Kim, Yeong Shik Kim, Dong Hyun Eur-J-Biochem. 2002 June; 269(12): 2934-40 0014-2956
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Repellent guidance of regenerating optic axons by chondroitin sulfate glycosaminoglycans in zebrafish. Author(s): Zentrum fur Molekulare Neurobiologie Hamburg, Universitat Hamburg, D20246 Hamburg, Germany.
[email protected] Source: Becker, Catherina G Becker, Thomas J-Neurosci. 2002 February 1; 22(3): 842-53 1529-2401
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Significance of chondroitin sulfate isomers in the synovial fluid of osteoarthritis patients. Author(s): Department of Orthopaedic Surgery, Nippon Medical School, 1-1-5 Sendagi, Bunkyo-ku, Tokyo 113-8602, Japan. Source: Uesaka, Shinji Nakayama, Yoshihito Yoshihara, Kiyoshi Ito, Hiromoto J-OrthopSci. 2002; 7(2): 232-7 0949-2658
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Stability of a cisplatin-chondroitin sulfate A complex in plasma and kidney in terms of protein binding. Author(s): Faculty of Pharmaceutical Science, Kumamoto University, Japan. Source: Zhang, J S Shen Feng, M A Suenaga, A Otagiri, M Biol-Pharm-Bull. 2001 August; 24(8): 970-2 0918-6158
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TGF-beta(3)-induced chondroitin sulphate proteoglycan mediates palatal shelf adhesion. Author(s): Departamento de Anatomia Humana, Facultad de Medicina, Universidad de Valladolid, Valladolid 47005, Spain. Source: Gato, A Martinez, M L Tudela, C Alonso, I Moro, J A Formoso, M A Ferguson, M W Martinez Alvarez, C Dev-Biol. 2002 October 15; 250(2): 393-405 0012-1606
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The bioavailability and pharmacokinetics of glucosamine hydrochloride and low molecular weight chondroitin sulfate after single and multiple doses to beagle dogs. Author(s): Center for Drug Evaluation and Research, Food and Drug Administration, Rockville, MD, USA. Source: Adebowale, A Du, J Liang, Z Leslie, J L Eddington, N D Biopharm-Drug-Dispos. 2002 September; 23(6): 217-25 0142-2782
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The efficacy of chondroitin sulfate 0.2% in treating interstitial cystitis. Author(s): Department of Urology, Capital Health Region, Victoria, BC, Canada. Source: Steinhoff, G Ittah, B Rowan, S Can-J-Urol. 2002 February; 9(1): 1454-8 1195-9479
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The intensely positively charged perineuronal net in the adult rat brain, with special reference to its reactions to oxine, chondroitinase ABC, hyaluronidase and collagenase. Author(s): Section of Human Morphology, Biophysiological Science, Graduate School of Medicine and Dentistry, Okayama University, Japan.
[email protected] Source: Murakami, T Kosaka, M Sato, H Ohtsuka, A Taguchi, T Arch-Histol-Cytol. 2001 August; 64(3): 313-8 0914-9465
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Transcription of multiple var genes by individual, trophozoite-stage Plasmodium falciparum cells expressing a chondroitin sulphate A binding phenotype. Author(s): Australian Indonesia Medical Research Initiative (AusAID), Eijkman Institute for Molecular Biology, Eijkman Building, Jl. Diponegoro 69, Jakarta, Indonesia 10430.
[email protected] Source: Duffy, Michael F Brown, Graham V Basuki, Wanny Krejany, Efrosinia O Noviyanti, Rintis Cowman, Alan F Reeder, John C Mol-Microbiol. 2002 March; 43(5): 1285-93 0950-382X
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White matter extracellular matrix chondroitin sulfate/dermatan sulfate proteoglycans in multiple sclerosis. Author(s): Department of Pathology, Stanford University School of Medicine, California 94305, USA. Source: Sobel, R A Ahmed, A S J-Neuropathol-Exp-Neurol. 2001 December; 60(12): 1198207 0022-3069
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 chondroitin; 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: •
Minerals Boron Source: Prima Communications, Inc.www.personalhealthzone.com Chondroitin Source: Integrative Medicine Communications; www.drkoop.com Chondroitin Source: Prima Communications, Inc.www.personalhealthzone.com Chondroitin Source: WholeHealthMD.com, LLC.; www.wholehealthmd.com Hyperlink: http://www.wholehealthmd.com/refshelf/substances_view/0,1525,10017,00.html Glucosamine/chondroitin Source: Healthnotes, Inc.; www.healthnotes.com
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Food and Diet Cartilage Source: Prima Communications, Inc.www.personalhealthzone.com
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Chondroitin Sulfate Source: Healthnotes, Inc.; www.healthnotes.com
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CHAPTER 3. ALTERNATIVE MEDICINE AND CHONDROITIN Overview In this chapter, we will begin by introducing you to official information sources on complementary and alternative medicine (CAM) relating to chondroitin. At the conclusion of this chapter, we will provide additional sources.
The Combined Health Information Database The Combined Health Information Database (CHID) is a bibliographic database produced by health-related agencies of the U.S. federal government (mostly from the National Institutes of Health) that can offer concise information for a targeted search. The CHID database is updated four times a year at the end of January, April, July, and October. Check the titles, summaries, and availability of CAM-related information by using the “Simple Search” option at the following Web site: http://chid.nih.gov/simple/simple.html. In the drop box at the top, select “Complementary and Alternative Medicine.” Then type “chondroitin” (or synonyms) in the second search box. We recommend that you select 100 “documents per page” and to check the “whole records” options. The following was extracted using this technique: •
Complementary and Alternative Therapies for Rheumatic Disease Source: Hospital Practice. 36(4): 31-36. April 15, 2001. Summary: This journal article discusses some of the complementary and alternative therapies used for rheumatic disease. First, it briefly reviews patterns of complementary and alternative therapy use among rheumatology patients. Then, it highlights findings from clinical investigations of selected therapies, including glucosamine and chondroitin, dietary interventions, vitamin supplements, herbal preparations (willow bark, devil's claw, feverfew, and Chinese thunder god vine), and acupuncture. Finally, it discusses management concerns for physicians whose patients may be using complementary and alternative therapies. It includes a list of suggested questions to ask and information to give patients about nontraditional therapies. The article has 2 figures, 3 tables, and a suggested reading list.
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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 chondroitin 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 “chondroitin” (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 chondroitin: •
A fingerprinting method for chondroitin/dermatan sulfate and hyaluronan oligosaccharides. Author(s): Lauder RM, Huckerby TN, Nieduszynski IA. Source: Glycobiology. 2000 April; 10(4): 393-401. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10764827&dopt=Abstract
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A large chondroitin sulfate basement membrane-associated proteoglycan exists as a disulfide-stabilized complex of several proteins. Author(s): Iwata M, Carlson SS. Source: The Journal of Biological Chemistry. 1991 January 5; 266(1): 323-33. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=1985903&dopt=Abstract
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A monoclonal antibody which recognizes a glycosaminoglycan epitope in both dermatan sulfate and chondroitin sulfate proteoglycans of human skin. Author(s): Sorrell JM, Carrino DA, Baber MA, Asselineau D, Caplan AI. Source: The Histochemical Journal. 1999 August; 31(8): 549-58. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10507462&dopt=Abstract
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A randomized, double blind, placebo controlled trial of a topical cream containing glucosamine sulfate, chondroitin sulfate, and camphor for osteoarthritis of the knee. Author(s): Cohen M, Wolfe R, Mai T, Lewis D. Source: The Journal of Rheumatology. 2003 March; 30(3): 523-8. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12610812&dopt=Abstract
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A study on heterogeneity in molecular species of shark cartilage chondroitin sulfate C. Fractionation of the polysaccharide on Sepharose CL-4B in the presence of high concentrations of ammonium sulfate. Author(s): Ogamo A, Yamada T, Nagasawa K. Source: Carbohydrate Research. 1987 August 1; 165(2): 275-80. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=3117365&dopt=Abstract
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Analysis of polysulfated chondroitin disaccharides by high-performance liquid chromatography. Author(s): Seldin DC, Seno N, Austen KF, Stevens RL.
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Source: Analytical Biochemistry. 1984 August 15; 141(1): 291-300. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=6437272&dopt=Abstract •
Asthma exacerbation associated with glucosamine-chondroitin supplement. Author(s): Tallia AF, Cardone DA. Source: The Journal of the American Board of Family Practice / American Board of Family Practice. 2002 November-December; 15(6): 481-4. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12463294&dopt=Abstract
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Biosynthesis of bone proteins by fetal porcine calvariae in vitro. Rapid association of sulfated sialoproteins (secreted phosphoprotein-1 and bone sialoprotein) and chondroitin sulfate proteoglycan (CS-PGIII) with bone mineral. Author(s): Nagata T, Goldberg HA, Zhang Q, Domenicucci C, Sodek J. Source: Matrix. 1991 April; 11(2): 86-100. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=1649377&dopt=Abstract
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Calcium-induced activation and truncation of promatrix metalloproteinase-9 linked to the core protein of chondroitin sulfate proteoglycans. Author(s): Winberg JO, Berg E, Kolset SO, Uhlin-Hansen L. Source: European Journal of Biochemistry / Febs. 2003 October; 270(19): 3996-4007. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=14511382&dopt=Abstract
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Characteristic hexasaccharide sequences in octasaccharides derived from shark cartilage chondroitin sulfate D with a neurite outgrowth promoting activity. Author(s): Nadanaka S, Clement A, Masayama K, Faissner A, Sugahara K. Source: The Journal of Biological Chemistry. 1998 February 6; 273(6): 3296-307. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=9452446&dopt=Abstract
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Chondroitin sulfate A released from platelets blocks RANTES presentation on cell surfaces and RANTES-dependent firm adhesion of leukocytes. Author(s): Mack M, Pfirstinger J, Weber C, Weber KS, Nelson PJ, Rupp T, Maletz K, Bruhl H, Schlondorff D. Source: European Journal of Immunology. 2002 April; 32(4): 1012-20. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11920567&dopt=Abstract
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Chondroitin sulfate changes in puppy rib cartilage during the period of calcification. Author(s): Bowness JM, Jacobs M. Source: Can J Biochem. 1968 January; 46(1): 64-7. No Abstract Available. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=4966904&dopt=Abstract
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Chondroitin/dermatan sulphate promotes the survival of neurons from rat embryonic neocortex.
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Author(s): Kappler J, Junghans U, Koops A, Stichel CC, Hausser HJ, Kresse H, Muller HW. Source: The European Journal of Neuroscience. 1997 February; 9(2): 306-18. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=9058051&dopt=Abstract •
Chondroitinase ABC-resistant sulfated trisaccharides isolated from digests of chondroitin/dermatan sulfate chains. Author(s): Sugahara K, Takemura Y, Sugiura M, Kohno Y, Yoshida K, Takeda K, Khoo KH, Morris HR, Dell A. Source: Carbohydrate Research. 1994 March 4; 255: 165-82. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=8181005&dopt=Abstract
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Copolymers of chondroitin 4-sulfate and chondroitin 6-sulfate in chick embryo epiphyses and other cartilage. Author(s): Faltynek CR, Silbert JE. Source: The Journal of Biological Chemistry. 1978 November 10; 253(21): 7646-9. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=701280&dopt=Abstract
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Decreased sulfation of cellular chondroitin sulfate in response to activators of protein kinase C. Author(s): Carson DL, Baxter CS. Source: Biochemical and Biophysical Research Communications. 1986 March 28; 135(3): 909-14. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=3083814&dopt=Abstract
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Demonstration of immunogenic keratan sulphate in commercial chondroitin 6sulphate from shark cartilage. Implications for ELISA assays. Author(s): Moller HJ, Moller-Pedersen T, Damsgaard TE, Poulsen JH. Source: Clinica Chimica Acta; International Journal of Clinical Chemistry. 1995 May 15; 236(2): 195-204. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=7554286&dopt=Abstract
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Determination of the distribution of constituent disaccharide units within the chain near the linkage region of shark-cartilage chondroitin sulfate C. Author(s): Uchiyama H, Kikuchi K, Ogamo A, Nagasawa K. Source: Biochimica Et Biophysica Acta. 1987 December 7; 926(3): 239-48. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=3120783&dopt=Abstract
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Determining the efficacy of glucosamine and chondroitin for osteoarthritis. Author(s): O'Rourke M. Source: The Nurse Practitioner. 2001 June; 26(6): 44-6, 49-52. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11416939&dopt=Abstract
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Effect of chondroitin sulfate A and flavonoids on hypervitaminosis D in rats. Author(s): Robbins RC, Morrison LM, Simpson CF. Source: Proceedings of the Society for Experimental Biology and Medicine. Society for Experimental Biology and Medicine (New York, N. Y.). 1969 July; 131(3): 719-22. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=5306034&dopt=Abstract
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Effect of pre-loading oral glucosamine HCl/chondroitin sulfate/manganese ascorbate combination on experimental arthritis in rats. Author(s): Beren J, Hill SL, Diener-West M, Rose NR. Source: Experimental Biology and Medicine (Maywood, N.J.). 2001 February; 226(2): 144-51. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11446439&dopt=Abstract
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Evidence of block and randomly sequenced chondroitin polysaccharides: sequential enzymatic digestion and quantification using ion trap tandem mass spectrometry. Author(s): Desaire H, Sirich TL, Leary JA. Source: Analytical Chemistry. 2001 August 1; 73(15): 3513-20. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11510812&dopt=Abstract
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Glucosamine and chondroitin for osteoarthritis? Author(s): McAlindon T. Source: Bulletin on the Rheumatic Diseases. 2001 July; 50(7): 1-4. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11530541&dopt=Abstract
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Glucosamine and chondroitin for treating symptoms of osteoarthritis: evidence is widely touted but incomplete. Author(s): Towheed TE, Anastassiades TP. Source: Jama : the Journal of the American Medical Association. 2000 March 15; 283(11): 1483-4. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10732941&dopt=Abstract
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Glucosamine and chondroitin for treatment of osteoarthritis: a systematic quality assessment and meta-analysis. Author(s): McAlindon TE, LaValley MP, Gulin JP, Felson DT. Source: Jama : the Journal of the American Medical Association. 2000 March 15; 283(11): 1469-75. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10732937&dopt=Abstract
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Glucosamine and chondroitin sulfate are effective in the management of osteoarthritis. Author(s): Hungerford DS, Jones LC.
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Source: The Journal of Arthroplasty. 2003 April; 18(3 Suppl 1): 5-9. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12730919&dopt=Abstract •
Glucosamine and chondroitin sulfate supplementation to treat symptomatic disc degeneration: biochemical rationale and case report. Author(s): van Blitterswijk WJ, van de Nes JC, Wuisman PI. Source: Bmc Complementary and Alternative Medicine [electronic Resource]. 2003 June 10; 3(1): 2. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12797867&dopt=Abstract
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Glycosyl transferases in chondroitin sulphate biosynthesis. Effect of acceptor structure on activity. Author(s): Gundlach MW, Conrad HE. Source: The Biochemical Journal. 1985 March 15; 226(3): 705-14. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=3921015&dopt=Abstract
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Heterogeneity of the chondroitin sulfate portion of phosphacan/6B4 proteoglycan regulates its binding affinity for pleiotrophin/heparin binding growth-associated molecule. Author(s): Maeda N, He J, Yajima Y, Mikami T, Sugahara K, Yabe T. Source: The Journal of Biological Chemistry. 2003 September 12; 278(37): 35805-11. Epub 2003 July 02. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12840014&dopt=Abstract
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Identification and characterization of ligands for L-selectin in the kidney. I. Versican, a large chondroitin sulfate proteoglycan, is a ligand for L-selectin. Author(s): Kawashima H, Li YF, Watanabe N, Hirose J, Hirose M, Miyasaka M. Source: International Immunology. 1999 March; 11(3): 393-405. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10221651&dopt=Abstract
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Immunohistochemical investigation on the presence of chondroitin sulfate in calcification nodules of epiphyseal cartilage. Author(s): Bonucci E, Silvestrini G. Source: Eur J Histochem. 1992; 36(4): 407-22. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=1283829&dopt=Abstract
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In vivo chondroprotection and metabolic synergy of glucosamine and chondroitin sulfate. Author(s): Lippiello L, Woodward J, Karpman R, Hammad TA. Source: Clinical Orthopaedics and Related Research. 2000 December; (381): 229-40. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11127660&dopt=Abstract
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Isolation of reducing oligosaccharide chains from the chondroitin/dermatan sulfateprotein linkage region and preparation of analytical probes by fluorescent labeling with 2-aminobenzamide. Author(s): Sakaguchi H, Watanabe M, Ueoka C, Sugiyama E, Taketomi T, Yamada S, Sugahara K. Source: Journal of Biochemistry. 2001 January; 129(1): 107-18. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11134964&dopt=Abstract
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Methods for the study of the glycoproteins and proteoglycans of bone using bacterial collagenase. Determination of bone sialoprotein and chondroitin sulphate. Author(s): Herring GM. Source: Calcif Tissue Res. 1977 December 14; 24(1): 29-36. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=202375&dopt=Abstract
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Microheterogeneity of chondroitin sulfates from various cartilages. Author(s): Seno N, Anno K, Yaegashi Y, Okuyama T. Source: Connective Tissue Research. 1975; 3(1): 87-96. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=126131&dopt=Abstract
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Nature and distribution of chondroitin sulphate and dermatan sulphate proteoglycans in rabbit alveolar bone. Author(s): Takagi M, Maeno M, Yamada T, Miyashita K, Otsuka K. Source: The Histochemical Journal. 1996 May; 28(5): 341-51. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=8818681&dopt=Abstract
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Nutraceuticals as therapeutic agents in osteoarthritis. The role of glucosamine, chondroitin sulfate, and collagen hydrolysate. Author(s): Deal CL, Moskowitz RW. Source: Rheumatic Diseases Clinics of North America. 1999 May; 25(2): 379-95. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10356424&dopt=Abstract
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Oral absorption and bioavailability of ichthyic origin chondroitin sulfate in healthy male volunteers. Author(s): Volpi N. Source: Osteoarthritis and Cartilage / Oars, Osteoarthritis Research Society. 2003 June; 11(6): 433-41. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12801483&dopt=Abstract
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Physicochemical properties of chondroitin sulfate. II. Molecular weight dependence of intrinsic viscosity and sedimentation coefficient, and analysis as a semi-flexible coil. Author(s): Tanaka K.
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Source: Journal of Biochemistry. 1978 March; 83(3): 655-9. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=641030&dopt=Abstract •
Preformulation studies and characterization of proposed chondroprotective agents: glucosamine HCl and chondroitin sulfate. Author(s): Ebube NK, Mark W, Hahm H. Source: Pharmaceutical Development and Technology. 2002 November; 7(4): 457-69. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12503527&dopt=Abstract
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Preparation of a series of sulfated tetrasaccharides from shark cartilage chondroitin sulfate D using testicular hyaluronidase and structure determination by 500 MHz 1H NMR spectroscopy. Author(s): Sugahara K, Tanaka Y, Yamada S. Source: Glycoconjugate Journal. 1996 August; 13(4): 609-19. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=8872118&dopt=Abstract
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Proteinase activity in chondroitin lyase (chondroitinase) and endo-beta-Dgalactosidase (keratanase) preparations and a method to abolish their proteolytic effect on proteoglycan. Author(s): Oike Y, Kimata K, Shinomura T, Suzuki S. Source: The Biochemical Journal. 1980 October 1; 191(1): 203-7. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=6781490&dopt=Abstract
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Role of chondroitin 4-sulphate as a receptor for polycation induced human platelet aggregation. Author(s): Donato JL, Marcondes S, Antunes E, Nogueira MD, Nader HB, Dietrich CP, Rendu F, de Nucci G. Source: British Journal of Pharmacology. 1996 December; 119(7): 1447-53. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=8968554&dopt=Abstract
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Specificity studies of bacterial sulfatases by means of structurally defined sulfated oligosaccharides isolated from shark cartilage chondroitin sulfate D. Author(s): Sugahara K, Kojima T. Source: European Journal of Biochemistry / Febs. 1996 August 1; 239(3): 865-70. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=8774737&dopt=Abstract
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Structural analysis of chick-embryo cartilage proteoglycan by selective degradation with chondroitin lyases (chondroitinases) and endo-beta-D-galactosidase (keratanase). Author(s): Oike Y, Kimata K, Shinomura T, Nakazawa K, Suzuki S. Source: The Biochemical Journal. 1980 October 1; 191(1): 193-207. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=6781489&dopt=Abstract
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Structural analysis of unsaturated hexasaccharides isolated from shark cartilage chondroitin sulfate D that are substrates for the exolytic action of chondroitin ABC lyase. Author(s): Sugahara K, Nadanaka S, Takeda K, Kojima T. Source: European Journal of Biochemistry / Febs. 1996 August 1; 239(3): 871-80. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=8774738&dopt=Abstract
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Structural and symptomatic efficacy of glucosamine and chondroitin in knee osteoarthritis: a comprehensive meta-analysis. Author(s): Richy F, Bruyere O, Ethgen O, Cucherat M, Henrotin Y, Reginster JY. Source: Archives of Internal Medicine. 2003 July 14; 163(13): 1514-22. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12860572&dopt=Abstract
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Structural characterisation of two hexasaccharides and an octasaccharide from chondroitin sulphate C containing the unusual sequence (4-sulpho)-Nacetylgalactosamine-beta1-4-(2-sulpho)-glucuronic acid-beta1-3-(6-sulpho)-Nacetylgalactosamine. Author(s): Chai W, Lawson AM, Gradwell MJ, Kogelberg H. Source: European Journal of Biochemistry / Febs. 1998 January 15; 251(1-2): 114-21. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=9492275&dopt=Abstract
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Structural studies on sulfated oligosaccharides derived from the carbohydrate-protein linkage region of chondroitin 6-sulfate proteoglycans of shark cartilage. I. Six compounds containing 0 or 1 sulfate and/or phosphate residues. Author(s): Sugahara K, Ohi Y, Harada T, de Waard P, Vliegenthart JF. Source: The Journal of Biological Chemistry. 1992 March 25; 267(9): 6027-35. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=1556114&dopt=Abstract
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Structural studies on sulfated oligosaccharides derived from the carbohydrate-protein linkage region of chondroitin 6-sulfate proteoglycans of shark cartilage. II. Seven compounds containing 2 or 3 sulfate residues. Author(s): de Waard P, Vliegenthart JF, Harada T, Sugahara K. Source: The Journal of Biological Chemistry. 1992 March 25; 267(9): 6036-43. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=1556115&dopt=Abstract
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Structural studies on the chondroitinase ABC-resistant sulfated tetrasaccharides isolated from various chondroitin sulfate isomers. Author(s): Sugahara K, Shigeno K, Masuda M, Fujii N, Kurosaka A, Takeda K. Source: Carbohydrate Research. 1994 March 4; 255: 145-63. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=8181004&dopt=Abstract
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Structure of chondroitin sulfates. Analyses of the products formed from chondroitin sulfates A and C by the action of the chondroitinases C and AC from Flavobacterium
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heparinum. Author(s): Michelacci YM, Dietrich CP. Source: Biochimica Et Biophysica Acta. 1976 December 21; 451(2): 436-43. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=999863&dopt=Abstract •
Sulfated polysaccharides (chondroitin sulfate and carrageenan) plus glucosamine sulfate are potent inhibitors of HIV. Author(s): Konlee M. Source: Posit Health News. 1998 Fall; (No 17): 4-7. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11366556&dopt=Abstract
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Suppression of atherogenesis in hypercholesterolemic rabbits by chondroitin-6sulfate. Author(s): Matsushima T, Nakashima Y, Sugano M, Tasaki H, Kuroiwa A, Koide O. Source: Artery. 1987; 14(6): 316-37. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=3118854&dopt=Abstract
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The DSD-1 carbohydrate epitope depends on sulfation, correlates with chondroitin sulfate D motifs, and is sufficient to promote neurite outgrowth. Author(s): Clement AM, Nadanaka S, Masayama K, Mandl C, Sugahara K, Faissner A. Source: The Journal of Biological Chemistry. 1998 October 23; 273(43): 28444-53. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=9774473&dopt=Abstract
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The effect of glucosamine-chondroitin supplementation on glycosylated hemoglobin levels in patients with type 2 diabetes mellitus: a placebo-controlled, double-blinded, randomized clinical trial. Author(s): Scroggie DA, Albright A, Harris MD. Source: Archives of Internal Medicine. 2003 July 14; 163(13): 1587-90. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12860582&dopt=Abstract
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The role of glucosamine sulfate and chondroitin sulfates in the treatment of degenerative joint disease. Author(s): Kelly GS. Source: Alternative Medicine Review : a Journal of Clinical Therapeutic. 1998 February; 3(1): 27-39. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=9600024&dopt=Abstract
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The unusual tetrasaccharide sequence GlcA beta 1-3GalNAc(4-sulfate)beta 1-4GlcA(2sulfate)beta 1-3GalNAc(6-sulfate) found in the hexasaccharides prepared by testicular hyaluronidase digestion of shark cartilage chondroitin sulfate D. Author(s): Nadanaka S, Sugahara K.
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Source: Glycobiology. 1997 March; 7(2): 253-63. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=9134432&dopt=Abstract
Additional Web Resources A number of additional Web sites offer encyclopedic information covering CAM and related topics. The following is a representative sample: •
Alternative Medicine Foundation, Inc.: http://www.herbmed.org/
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AOL: http://search.aol.com/cat.adp?id=169&layer=&from=subcats
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Chinese Medicine: http://www.newcenturynutrition.com/
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drkoop.com: http://www.drkoop.com/InteractiveMedicine/IndexC.html
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Family Village: http://www.familyvillage.wisc.edu/med_altn.htm
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Google: http://directory.google.com/Top/Health/Alternative/
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Healthnotes: http://www.healthnotes.com/
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MedWebPlus: http://medwebplus.com/subject/Alternative_and_Complementary_Medicine
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Open Directory Project: http://dmoz.org/Health/Alternative/
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HealthGate: http://www.tnp.com/
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WebMDHealth: http://my.webmd.com/drugs_and_herbs
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WholeHealthMD.com: http://www.wholehealthmd.com/reflib/0,1529,00.html
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Yahoo.com: http://dir.yahoo.com/Health/Alternative_Medicine/
The following is a specific Web list relating to chondroitin; 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 Atherosclerosis Source: Healthnotes, Inc.; www.healthnotes.com Heart Attack Source: Healthnotes, Inc.; www.healthnotes.com High Cholesterol Source: Healthnotes, Inc.; www.healthnotes.com High Cholesterol Source: Prima Communications, Inc.www.personalhealthzone.com
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Kidney Stones Source: Healthnotes, Inc.; www.healthnotes.com Osteoarthritis Source: Healthnotes, Inc.; www.healthnotes.com Osteoarthritis Source: Integrative Medicine Communications; www.drkoop.com Osteoarthritis Source: Prima Communications, Inc.www.personalhealthzone.com Peripheral Vascular Disease Source: Healthnotes, Inc.; www.healthnotes.com Sprains and Strains Source: Healthnotes, Inc.; www.healthnotes.com Wound Healing Source: Healthnotes, Inc.; www.healthnotes.com •
Herbs and Supplements Aortic Glycosaminoglycans Source: Prima Communications, Inc.www.personalhealthzone.com Glucosamine Source: Healthnotes, Inc.; www.healthnotes.com Glucosamine Source: Integrative Medicine Communications; www.drkoop.com Glucosamine Source: Prima Communications, Inc.www.personalhealthzone.com Glucosamine Source: WholeHealthMD.com, LLC.; www.wholehealthmd.com Hyperlink: http://www.wholehealthmd.com/refshelf/substances_view/0,1525,790,00.html Same (s-adenosylmethionine) Source: Prima Communications, Inc.www.personalhealthzone.com Withania Ashwagandha Alternative names: Ashwagandha; Withania somnifera L. 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 CHONDROITIN Overview In this chapter, we will give you a bibliography on recent dissertations relating to chondroitin. 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 “chondroitin” (or a synonym) in their titles. To accurately reflect the results that you might find while conducting research on chondroitin, we have not necessarily excluded nonmedical dissertations in this bibliography.
Dissertations on Chondroitin 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 chondroitin. 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: •
Analyses of the Pasteurella Multocida Hyaluronan and Chondroitin Synthases Catalytic Mechanism by Jing, Wei; , Phd from The University of Oklahoma Health Sciences Center, 2002, 129 pages http://wwwlib.umi.com/dissertations/fullcit/3064174
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Expression and Influence of Versican Chondroitin Sulfate Proteoglycan on Early Chicken Ear Development by Heng, Channarith C.; Phd from Temple University, 2002, 78 pages http://wwwlib.umi.com/dissertations/fullcit/3040321
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Mechanistic Studies of Chondroitin Ac Lyase from Flavobacterium Heparinum by Rye, Carl S.; Phd from The University of British Columbia (canada), 2002, 196 pages http://wwwlib.umi.com/dissertations/fullcit/NQ75074
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Multiple Domains of the Ng2 Chondroitin Sulfate Proteoglycan Inhibit Axonal Growth and Regeneration by Ughrin, Yvonne Meghann; Phd from State University of New York at Stony Brook, 2002, 137 pages http://wwwlib.umi.com/dissertations/fullcit/3088062
Keeping Current Ask the medical librarian at your library if it has full and unlimited access to the ProQuest Digital Dissertations database. From the library, you should be able to do more complete searches via http://wwwlib.umi.com/dissertations.
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CHAPTER 5. CLINICAL TRIALS AND CHONDROITIN Overview In this chapter, we will show you how to keep informed of the latest clinical trials concerning chondroitin.
Recent Trials on Chondroitin The following is a list of recent trials dedicated to chondroitin.8 Further information on a trial is available at the Web site indicated. •
Glucosamine/Chondroitin Arthritis Intervention Trial (GAIT) Condition(s): Osteoarthritis Study Status: This study is currently recruiting patients. Sponsor(s): Department of Veterans Affairs; Department of Veterans Affairs Cooperative Studies Program; National Institutes of Health (NIH); National Center for Complementary and Alternative Medicine (NCCAM) Purpose - Excerpt: This study will determine whether glucosamine, chondroitin sulfate and/or the combination of glucosamine and chondroitin sulfate are more effective than placebo and whether the combination is more effective than glucosamine or chondroitin sulfate alone in the treatment of knee pain associated with osteoarthritis (OA) of the knee. These substances, marketed in the United States as nutritional supplements, have been widely touted by the lay press and by anecdotal personal experience as effective in treating OA. To date, however, only a few small studies have been published in the worldwide literature. The study proposed herein has been carefully constructed to definitively determine the efficacy of these agents. Phase(s): Phase III Study Type: Interventional Contact(s): see Web site below Web Site: http://clinicaltrials.gov/ct/show/NCT00032890
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These are listed at www.ClinicalTrials.gov.
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Keeping Current on Clinical Trials The U.S. National Institutes of Health, through the National Library of Medicine, has developed ClinicalTrials.gov to provide current information about clinical research across the broadest number of diseases and conditions. The site was launched in February 2000 and currently contains approximately 5,700 clinical studies in over 59,000 locations worldwide, with most studies being conducted in the United States. ClinicalTrials.gov receives about 2 million hits per month and hosts approximately 5,400 visitors daily. To access this database, simply go to the Web site at http://www.clinicaltrials.gov/ and search by “chondroitin” (or synonyms). While ClinicalTrials.gov is the most comprehensive listing of NIH-supported clinical trials available, not all trials are in the database. The database is updated regularly, so clinical trials are continually being added. The following is a list of specialty databases affiliated with the National Institutes of Health that offer additional information on trials: •
For clinical studies at the Warren Grant Magnuson Clinical Center located in Bethesda, Maryland, visit their Web site: http://clinicalstudies.info.nih.gov/
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For clinical studies conducted at the Bayview Campus in Baltimore, Maryland, visit their Web site: http://www.jhbmc.jhu.edu/studies/index.html
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For cancer trials, visit the National Cancer Institute: http://cancertrials.nci.nih.gov/
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For eye-related trials, visit and search the Web page of the National Eye Institute: http://www.nei.nih.gov/neitrials/index.htm
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For heart, lung and blood trials, visit the Web page of the National Heart, Lung and Blood Institute: http://www.nhlbi.nih.gov/studies/index.htm
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For trials on aging, visit and search the Web site of the National Institute on Aging: http://www.grc.nia.nih.gov/studies/index.htm
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For rare diseases, visit and search the Web site sponsored by the Office of Rare Diseases: http://ord.aspensys.com/asp/resources/rsch_trials.asp
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For alcoholism, visit the National Institute on Alcohol Abuse and Alcoholism: http://www.niaaa.nih.gov/intramural/Web_dicbr_hp/particip.htm
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For trials on infectious, immune, and allergic diseases, visit the site of the National Institute of Allergy and Infectious Diseases: http://www.niaid.nih.gov/clintrials/
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For trials on arthritis, musculoskeletal and skin diseases, visit newly revised site of the National Institute of Arthritis and Musculoskeletal and Skin Diseases of the National Institutes of Health: http://www.niams.nih.gov/hi/studies/index.htm
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For hearing-related trials, visit the National Institute on Deafness and Other Communication Disorders: http://www.nidcd.nih.gov/health/clinical/index.htm
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For trials on diseases of the digestive system and kidneys, and diabetes, visit the National Institute of Diabetes and Digestive and Kidney Diseases: http://www.niddk.nih.gov/patient/patient.htm
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For drug abuse trials, visit and search the Web site sponsored by the National Institute on Drug Abuse: http://www.nida.nih.gov/CTN/Index.htm
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For trials on mental disorders, visit and search the Web site of the National Institute of Mental Health: http://www.nimh.nih.gov/studies/index.cfm
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For trials on neurological disorders and stroke, visit and search the Web site sponsored by the National Institute of Neurological Disorders and Stroke of the NIH: http://www.ninds.nih.gov/funding/funding_opportunities.htm#Clinical_Trials
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CHAPTER 6. PATENTS ON CHONDROITIN Overview Patents can be physical innovations (e.g. chemicals, pharmaceuticals, medical equipment) or processes (e.g. treatments or diagnostic procedures). The United States Patent and Trademark Office defines a patent as a grant of a property right to the inventor, issued by the Patent and Trademark Office.9 Patents, therefore, are intellectual property. For the United States, the term of a new patent is 20 years from the date when the patent application was filed. If the inventor wishes to receive economic benefits, it is likely that the invention will become commercially available within 20 years of the initial filing. It is important to understand, therefore, that an inventor’s patent does not indicate that a product or service is or will be commercially available. The patent implies only that the inventor has “the right to exclude others from making, using, offering for sale, or selling” the invention in the United States. While this relates to U.S. patents, similar rules govern foreign patents. In this chapter, we show you how to locate information on patents and their inventors. If you find a patent that is particularly interesting to you, contact the inventor or the assignee for further information. IMPORTANT NOTE: When following the search strategy described below, you may discover non-medical patents that use the generic term “chondroitin” (or a synonym) in their titles. To accurately reflect the results that you might find while conducting research on chondroitin, we have not necessarily excluded nonmedical patents in this bibliography.
Patents on Chondroitin By performing a patent search focusing on chondroitin, you can obtain information such as the title of the invention, the names of the inventor(s), the assignee(s) or the company that owns or controls the patent, a short abstract that summarizes the patent, and a few excerpts from the description of the patent. The abstract of a patent tends to be more technical in nature, while the description is often written for the public. Full patent descriptions contain much more information than is presented here (e.g. claims, references, figures, diagrams, etc.). We will tell you how to obtain this information later in the chapter. The following is an 9Adapted
from the United States Patent and Trademark Office: http://www.uspto.gov/web/offices/pac/doc/general/whatis.htm.
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example of the type of information that you can expect to obtain from a patent search on chondroitin: •
Affinity chromatographic matrix containing non-covalently bound ligand for purification of biological material Inventor(s): Khandke; Kiran Manohar (Nanuet, NY) Assignee(s): American Cyanamid Company (Madison, NJ) Patent Number: 6,150,151 Date filed: August 17, 1994 Abstract: An affinity chromatographic matrix for purification of a biological material is provided having an ionically charged polymeric ligand such as glycoaminoglycan noncovalently bound directly by an ionic bond to an oppositely ionically charged group on a chromatographic matrix. Having the ligand non-covalently bound to the matrix by an ionic bond, allows the ligand to be easily washed off the matrix and replaced for subsequent purifications without having to replace the matrix. A biological material in a crude mixture is purified by non-covalently binding the material to the bound ligand and dissociating the material from the ligand. Matrices that may be used include crosslinked agarose, crosslinked dextran, crosslinked cellulose, crosslinked dextran and bisacrylamide, or matrices based on silica or plastic polymers. The charged group may be a quaternary amine or diethylaminoethyl group. Chondroitinase is purified from a crude mixture containing contaminating proteins by contacting the crude mixture with an anion exchange resin containing chondroitin sulfate non-covalently bound by an ionic bond. Chondroitinase non-covalently binds to the bound chondroitin sulfate and contaminating proteins pass through the matrix. Chondroitinase is then dissociated from the matrix. Excerpt(s): The present invention relates to methods for purifying biological molecules employing affinity chromatography. In particular, the present invention is directed to an affinity chromatography technique employing a highly charged polymeric ligand noncovalently bound to a charged support. Affinity chromatography is a separation technique which is based on the specific binding properties of biological molecules. Briefly, the methodology of affinity chromatography involves the attachment of a specific ligand to an insoluble support or matrix to form a conjugate which is then contacted with a "feed" containing the substance to be purified either in a column or batch configuration. Contact of the feed with the conjugate results in the substance that reacts specifically with the ligand becoming attached to the conjugate with all the remaining components of the feed passing through the column in the void volume. The adsorbed substance is then eluted from the column by imposing conditions which dissociate it from the conjugated ligand. Preferably, the column can then be recycled and the affinity adsorbent reused for additional purifications. Generally speaking, an affinity chromatography system has several components; a support for attaching the ligand, which is generally made from a polysaccharide but may also be made from other materials such as polyacrylamide gel, silica, other polymers or glass; optionally a spacer or "arm" between the ligand or support used to contribute to the binding of macromolecules such as proteins to affinity columns; and the ligand which is specifically designed based on its capability to bind to the substance to be purified. The ligand may be an enzyme, co-enzyme, the substrate or inhibitor of an enzyme, an antibody, an antigen, and the like. Web site: http://www.delphion.com/details?pn=US06150151__
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Aminosugar and glycosaminoglycan composition for the treatment and repair of connective tissue Inventor(s): Henderson; Robert W. (Baldwin, MD) Assignee(s): Nutramax Laboratories, Inc. (Baltimore, MD) Patent Number: 6,492,349 Date filed: December 23, 1996 Abstract: A therapeutic composition for the protection, treatment and repair of connective tissue in mammals and a method for the treatment of connective tissue in mammals by the administration of the composition. The composition includes glucosamine and preferably chondroitin sulfate or fragments thereof. The composition optionally includes manganese ascorbate which catalyzes the production of collagen and proteoglycans from the glucosamine and chondroitin sulfate. Excerpt(s): The present invention relates to therapeutic compositions for the repair of connective tissue in humans and animals and, in particular to nutraceutical compositions capable of promoting chondroprotection, the repair and replacement of human and animal connective tissue. The connective tissues of humans and animals are constantly subjected to stresses and strains from mechanical forces that can result in afflictions, such as arthritis, joint inflammation and stiffness. Such afflictions are especially acute in joints, such as the neck, back, arms, hips, ankles and feet. Indeed, connective tissue afflictions are quite common, presently affecting millions of Americans. Further, such afflictions can be both painful and, in their extreme, debilitating. The treatment of connective tissue afflictions can be quite problematic. A simple decrease in the stress to which the connective tissue is subjected is often not usually an option, especially in the case of athletes and animals such as race horses. Thus, an interruption in the traumatic pathways can often not be achieved. Consequently, especially in the case of human athletes and animals, treatment is often directed at controlling the symptoms of the afflictions and not their causes, regardless of the stage of the degenerative process. Web site: http://www.delphion.com/details?pn=US06492349__
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Attenuation of wound healing processes Inventor(s): Bennett; Clark (Pierrefonds, CA), Broughton; Richard (Montreal, CA), Danagher; Pamela (Montreal, CA), Vlodavsky; Israel (Jerusalem, IL), Zimmermann; Joseph (Elm Grove, WI) Assignee(s): Ibex Technologies R and D, Inc. (Montreal, CA) Patent Number: 5,997,863 Date filed: July 8, 1994 Abstract: Glycosaminoglycans, including heparinases 1, 2 and 3 as well as chondroitinases AC and B from the Gram negative bacteria Flavobacterium heparinum, can be used either separately or in combination to manipulate cell proliferation. In one embodiment, heparinases are administered to degrade heparan sulfate components of the extracellular matrix, thereby allowing the heparin binding growth factors which are stored in the extracellular matrix to migrate to adjacent cells. The mobility of chemoattractant agents, growth factors and cells also can be increased by treating tissues with glycosaminoglycan degrading enzymes, both chondroitinases and heparinases.
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The enzymatic removal of chondroitin sulfates from cell surfaces effectively increases the availability of growth factor receptors on the cell's surface. Selectively removing heparan sulfate from cell surfaces while leaving the extracellular matrix intact, conversely, inhibits cell proliferation by down regulating the cell's response to growth factors. This is achieved by targeting heparin or heparan sulfate degrading activities to the cell surface. Targeting the heparin degrading activity can be achieved by genetically engineering a ligand binding functionality into the heparinase proteins, or by physically controlling the localized enzyme concentration through the method of administration. Excerpt(s): The present invention describes a methodology for the use of glycosaminoglycan degrading enzymes to modulate events in the wound healing process. Growth factors are naturally occurring polypeptides that elicit hormone type modulation of cell proliferation and differentiation. The mechanism by which these events transpire is typically initiated by the growth factor contacting specific receptors or receptor systems which are located on the cell surface. The sequence of intracellular events that occur subsequent to the receptor/growth factor interaction are responsible for mitogenic and differentiating responses by the cell. These mechanisms are not fully understood but may include activation of tyrosine kinases, nucleotide metabolism and variations in cell electrolyte levels (Burgess and Macaig, Ann. Rev. Biochem, 58:575-606, 1989). For most cell types, events of mitogenesis and differentiation are subdued in the normal adult animal. These growth factor mediated events are more commonly associated with developing organisms, during wound healing processes or in various disease states including cancer and vascular disease. For example, the normal turnover rate of endothelial cells, including the lining of microvessels and arteries, is measured in thousands of days. During normal wound healing however, these endothelial cells proliferate rapidly, with a turnover rate of approximately five days (Folkman and Shing, J. Biol. Chem. 267(16):10931-10934, 1992). The increase in proliferation that occurs during wound healing appears to be the result of an increase in the local concentration of various angiogenic molecules, including growth factors. Web site: http://www.delphion.com/details?pn=US05997863__ •
Bioactive concentrate, its producing method and certain drug compositions containing also chondroitin sulphate Inventor(s): Arizan; Dan-Etienne (Bucharest, RO), Carasava; Marian (Bucharest, RO), Ionita-Manzatu; Vasile (Bucharest, RO), Manzatu; Ioan (Bucharest, RO), Panait; Maria (Constanta, RO), Scarlat; Irina-Gabriela (Bucharest, RO) Assignee(s): S. C. Tehman S.R.L. (Bucharest, RO) Patent Number: 5,965,151 Date filed: October 3, 1997 Abstract: This bioactive concentrate is an active substance--aqueous solution or lyophilized powder--consisting of anti-hyaluronidase and antiinflammatory mucopolysaccharide polymers and an addition of restitutive and anti-hyaluronidase chondroitinsulphate, which has a pH=4-6 and antihyaluronidase activity. The bioactive concentrate producing method consists in a two--phased treatment of animal-originated connective cartilaginous tissues such as bovine and sheep trachea, umbilical cord, young animal tendons, bowels, testicles or sea organisms, with phenol solution and the solution resulted is concentrated by vacuum evaporation and then defatted; after filtering, the supernatant obtained is treated for deproteinization, the ion excess is removed by passing through ion exchanger column, the alcohol solution is concentrated
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to remove alcohol until reaching a volume of 70% as against the aqueous solution subject to proteinzation. Drug compsitions contain the bioactive concentrate--solution or in lyophilized state--associated with synergic substances such as: heparin, sodium or lysin acetylsallicylate, ascorbic acid, vitamin E,"I"-like structured water, benzyl alcohol, propylene glycocou, plant extracts (Achillea, Calendula, Matricaria, Plantago, Hypericum) and usual excipients, being conditioned in the form of intramuscular or intraarticular injections, ointment, gel and suppositories. Finally the histamines are removed and chondroitin sulphate is added up to the concentration required. Excerpt(s): This invention relates to a bioactive concentrate, a method of producing same and pharmaceutical compositions containing the bioactive concentrate for treatment of degenerative diseases, including rheumatism, arthropaties and other related diseases. A complex of anti-hyaluronidase substances has been derived from several natural products, such as small fish containing amino acids, whole glucides, glycogen chondroitinsulphate, phenol, hypotensive substances, with an antihyaluronidase activity of a minimum of 50 I.U/ml. The method whereby the complex is produced consists of a two-phased treatment of se fish with 0.5% phenol solution, over a period of 24 h, the extracts brought together are vacuum concentrated at a maximum 40.degree. C., then they are treated with an equal ethanol 96.sup.c volume; the precipitate is removed and the supernatant obtained is treated with celite, filtered, vacuum-concentrated at a maximum 40.degree. C., then solvent-extracted--treated and after removing the solvent the supernatant is treated with phenol up to a value of 4.55.5%. Web site: http://www.delphion.com/details?pn=US05965151__ •
Cartilage enhancing food supplements and methods of preparing the same Inventor(s): Stone; Kevin R. (Mill Valley, CA) Assignee(s): Joint Juice, Inc. (San Francisco, CA) Patent Number: 6,432,929 Date filed: June 21, 2000 Abstract: A food supplement, either in the form of a snack bar or a beverage, which contains one or more cartilage enhancing supplements is provided. The cartilage supplements include chondroitin, glucosamine, and hyaluronic acid. The food supplement may additionally be fortified with cetyl myristoleate. The beverage is a mixture of a juice drink base which may include a water-based fruit flavored juice prepared using a pasteurization process at a relatively high temperature and a cartilage supplement solution which includes a cartilage supplement prepared at a relatively low temperature. The beverage may be carbonated, non-carbonated or concentrated. The preferred cartilage supplement is glucosamine, preferably associated with a counter ion, more preferably as glucosamine HCl. Excerpt(s): The present invention relates to food supplements, such for example, snack bars and beverages which are fortified with one or more cartilage supplements. Nutritional bars and energy drinks are convenient nutritional supplements, particularly for those persons too busy to eat regular meals and for hikers, cyclists, runners or other athletes who need prepackaged, ready-to-eat, high-energy snacks while they are exercising. Such bars and drinks are also convenient nutritional supplements for the elderly who need prepackaged, ready-to-eat snacks. Additionally, such food supplements can supply consumers with the necessary vitamins and minerals specified
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in the recommended daily allowances provided by the U.S. government. By way of example, U.S. Pat. No. 4,543,262 discloses a high protein, low or no lactose, vitamin and mineral fortified, nutritionally-balanced snack bar. Additionally, U.S. Pat. No. 3,814,819 teaches a protein-fortified food bar composed of several baked crisp wafers layered on top of the other with a creamy filling between them. The creamy filling contains added vitamins, providing twenty-five percent (25%) of the recommended daily allowance of vitamins and minerals. U.S. Pat. No. 4,152,462 teaches a highly nutritious protein and vitamin enriched food bar, having a marshmallow base. Lastly, U.S. Pat. No. 3,901,799 discloses a high protein chocolate bar. Caseinate and peanut butter are added to a mixture of chocolate and cocoa butter. Vitamins compatible with the ingredients, it is disclosed, can be added to the snack bar. Web site: http://www.delphion.com/details?pn=US06432929__ •
Chondroitin lyase enzymes Inventor(s): Bennett; D. Clark (Pierrefonds, CA), Fink; Dominique (Chambord, CA), Gu; Kangfu (Dollard des Ormeaux, CA), Laliberte; Maryse (Boisbriand, CA), Linhardt; Robert (Iowa City, IA), Tkalec; Anna Lydia (Montreal, CA), Zimmermann; Joseph (Elm Grove, WI) Assignee(s): IBEX Technologies R and D, Inc. (Montreal, CA) Patent Number: 6,054,569 Date filed: September 17, 1997 Abstract: The present invention describes a method for the production of two highly purified enzymes capable of degrading chondroitin sulfate polysaccharides. A multistep purification method incorporating cell disruption, cation exchange chromatography, affinity chromatography, hydroxylapatite chromatography, high resolution ion exchange chromatography and size exclusion is outlined. A 77,000.+.5,000 Dalton protein capable of degrading chondroitin sulfates A and C and a 55,000.+.2,300 Dalton protein capable of degrading dermatan sulfate were isolated. The genes encoding these enzymes, chondroitinase AC and chondroitinase B, respectively, have been cloned and methods for their use are described. Excerpt(s): The present invention is the purification and cloning of chondroitin lyase enzymes found in Flavobacterium heparinum. Glycosaminoglycans are unbranched polysaccharides consisting of alternating hexosamine and hexuronic residues which carry sulfate groups in different positions. This class of molecules can be divided into three families according to the composition of the disaccharide backbone. These are: heparin/heparan sulfate [HexA-GlcNAc(SO.sub.4)]; chondroitin sulfate [HexAGalNAc]; and keratan sulfate [Gal-GlcNAc]. The chondroitin sulfate family includes seven sub-types designated unsulfated chondroitin sulfate, oversulfated chondroitin sulfate and chondroitin sulfates A-E which vary in the number and position of their sulfate functional groups. Additionally, chondroitin sulfate B, also referred to as dermatan sulfate, differs in that iduronic acid is the predominant residue in the alternative hexuronic acid position. Chondroitin sulfates A, B and C are the predominant forms found in mammals and may be involved in the modulation of various biological activities including cell differentiation, adhesion, enzymatic pathways and hormone interactions. The presence of chondroitin sulfate proteoglycans is elevated in the later stages of cell growth in response to tissue and vessel damage, as reported by Yeo, et al., Am. J. Pathol. 138:1437-1450, 1991, Richardson and Hatton, Exp. Mol. Pathol. 58:77-95, 1993 and Forrester, et al., J. Am. Coll. Cardiol. 17:758-769, 1991. Chondroitin
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sulfates also have been associated with events involved in the progression of vascular disease and lipoprotein uptake as described by Tabas, et al., J. Biol. Chem., 268(27):20419-20432, 1993. Web site: http://www.delphion.com/details?pn=US06054569__ •
Chondroitin sulfate as a marker of bone resorption Inventor(s): Klock; John C. (Nicasio, CA) Assignee(s): BioMarin Pharmaceuticals (Novato, CA) Patent Number: 6,287,789 Date filed: February 8, 1999 Abstract: The subject invention provides methods and kits for detecting increased bone resorption in patients. These methods and kits use chondroitin sulfate, a glycosaminoglycan, as a marker for bone resorption. Levels of chondroitin sulfate are detected in samples of urine or serum taken from patients. Measurements of chondroitin sulfate levels are made by methods such as fluorophore-assisted carbohydrate electrophoresis (FACE). Knowledge of increased bone resorption rates is useful in diagnosis of bone disorders such as osteoporosis. Excerpt(s): The subject invention is in the field of medical diagnostics and carbohydrate chemistry and biochemistry. In particular, the invention describes the use of chondroitin sulfate, a biological component from human body fluids such as blood and urine, as a marker for bone resorption. Carbohydrates play a number of important roles in the functioning of living organisms. In addition to their metabolic roles, carbohydrates are structural components of the human body covalently attached to numerous other entities such as proteins and lipids (called glycoconjugates). For example, human bone consists of hydroxyapatite, minerals, collagen protein, and a proteoglycan matrix. The carbohydrate portion of this proteoglycan matrix imparts essential properties to the bone structure and plays a role in bone metabolism. Bone resorption is an important process in human health. Children have extremely high bone resorption rates due to their overall high rate of bone metabolism associated with growth. Bettica et al. (1992), Clinical Chemistry 38:2313-2518; Hanson et al. (1992), J. Bone Mineral Res. 7:1251-58. However, in adults, high rates of bone resorption are generally associated with metabolic bone disorders, such as primary hyperparathyroidism, osteomalacia, and Paget's disease. Seyedin et al. (1993), J. Bone Mineral Res. 8:635-41; Hanson et al. (1992), supra. Paget's disease, in particular, is characterized by a very high of bone resorption. Bettica et al. (1992), supra; Seyedin et al. (1993), supra. Although these diseases are significant, they affect a relatively small proportion of the population. The most widespread disease that is associated with a high rate of bone resorption in adults is osteoporosis; however, the increase in bone resorption associated with osteoporosis is much lower than that of Paget's disease, and hence is much more difficult to detect using conventional methods. Web site: http://www.delphion.com/details?pn=US06287789__
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Chondroitin sulfate composition and method for wound treatment Inventor(s): Petito; George D. (1890 Bucknell Dr., Bethlehem, PA 18015) Assignee(s): none reported Patent Number: 5,929,050 Date filed: February 27, 1998 Abstract: A method and composition for treating open wounds. The method includes thorough cleaning of the wound, and application of the composition and a sterile dressing. The composition and dressing may be changed as needed. The composition is an aqueous solution of 90-110 mg/mL glycosaminoglycan. Preferably, chondroitin sulfate will be used. Additional components, that may be added singly or in combination, include collagen, other glycosaminoglycans, glucosamine hydrochloride, glucosamine sulfate, certain buffering agents, and certain preservatives. Using the solution of this invention on acute or chronic open wounds aids the natural healing process, thereby increases the rate of healing. Excerpt(s): The present invention relates to compositions and methods that increase the rate at which a wound will heal. Glycosaminoglycans (GAGs) are polysaccharides found in vertebrate and invertebrate animals. Several GAGs have been found in tissues and fluids of vertebrate animals. The known GAGS are chondroitin sulfate, keratan sulfate, dermatan sulfate, hyaluronic acid, heparin and heparan sulfate. Chondroitin sulfate is a linear polymer occurring in several isomers, named for location of the sulfate group. Chondroitin-4 sulfate is found in nasal and tracheal cartilages of bovines and porcines. It is also found in the bones, flesh, blood, skin, umbilical cord, and urine of these animals. Chondroitin-6 sulfate has been isolated from the skin, umbilical cord, and cardiac valves of these animals. Chondroitin-6 sulfate has the same composition, but slightly different physical properties from chondroitin-4 sulfate. These are the most common isomers used in the present invention. The polymer is also known as chondroitin polysulfate sodium, chondron, sodium chondroitin poly sulfate, and sodium chondroitin sulfate. For consistency, the term "chondroitin sulfate" will be used for all chondroitin sulfate isomers throughout this application. Chondroitin sulfate is involved in the binding of collagen and is also directly involved in the retention of moisture. These are both properties that aid the healing process. Web site: http://www.delphion.com/details?pn=US05929050__
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Chondroitin sulphate and chitosan compositions for treating rheumatic disorders Inventor(s): Derrieu; Guy (Cagnes-sur-Mer, FR), Pougnas; Jean-Luc (Saint Laurent du Var, FR) Assignee(s): Virbac (Carros, FR) Patent Number: 6,599,888 Date filed: February 22, 2002 Abstract: The subject of the present invention is the use of a preparation comprising:a) from 1 to 50% by weight, relative to the total weight of the preparation, of at least one compound chosen from chondroitin sulfates and their salts, andb) from 1 to 66% by weight, relative to the total weight of the preparation, of at least one compound chosen from chitosan, its salts, its derivatives and the salts of these derivatives, for the preparation of a composition for the prevention or treatment of rheumatic conditions by
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the general route, and, in particular, for the prevention or treatment of degenerative arthropathies. Excerpt(s): The subject of the present invention is the use of preparations based on chondroitin sulfate and chitosan for the preparation of compositions intended for the prevention or treatment of rheumatic conditions and, in particular, degenerative arthropathies, by the general route. The joints and the various connective tissues of which they consist (cartilages, fibrocartilages, synovial membranes, ligaments and the like) are constantly subjected to mechanical stresses and to stresses which may lead to inflammatory pathologies such as arthritis or degenerative pathologies such as osteoarthritis, which are responsible for their blockage. These conditions may be acute at the level of the joints in the neck, the shoulders, the back, the hips, the forelimbs such as the elbows and the wrists, the hindlimbs such as the knees and the ankles, as well as the fingers or the toes. These pathologies are very frequent and affect both humans and animals. Mainly two families of antiinflammatory compounds are used in human and veterinary rheumatology: the glucocorticosteroids and the NSAIDs (or nonsteroidal anti-inflammatory drugs: salycilates, indoles and related compounds, propionics, pyrazoles, anthranylines and the like). Although relieving pain and reducing the inflammatory state of connective tissues during their use, these compounds have only a pain-relieving function and do not allow a return to the normal state by the reconstitution of the tissues. Thus, these treatments are in the long term ineffective, or even harmful, because they block the natural processes for the defence of the body and lead to a destruction of the connective tissues. Web site: http://www.delphion.com/details?pn=US06599888__ •
Chrondroitin sulfate/sodium hyaluronate composition Inventor(s): Boyd; James E. (Barboursville, WV), Chang; Allison S. (Lesage, WV), Johnson; Richard M. (Huntington, WV), Koch; Harold O. (Barboursville, WV) Assignee(s): Nestle S.A. (Vevey, CH) Patent Number: 6,051,560 Date filed: April 3, 1992 Abstract: Chondroitin sulfate/soduim hyaluronate compositions exhibiting pseudoplastic behavior and non-Newtonian flow characteristics are disclosed. Excerpt(s): The invention relates to compositions obtained by adding chondroitin sulfate to sodium hyaluronate in aqueous buffer solution, or sodium hyaluronate to chondroitin sulfate in aqueous buffer solution. This invention relates to compositions for protecting both human and animal endothelial and epithelial cells which are subject to exposure to trauma. More particularly, this invention concerns compositions for protecting endothelial and epithelial cells in anticipation of surgical trauma using chondroitin sulfate/sodium hyaluronate compositions. Since human corneal endothelial cells are not known to reproduce, it is of vital importance to protect endothelia to prevent cell damage prior to subjection to anticipated trauma, such as surgery. Recent advances in ophthalmic surgery have increased the need to protect corneal endothelial cells which may be subject to irreversible destruction during such surgery. Of particular significance is the need to protect corneal endothelial cells during intraocular lens (IOL) implantation, corneal transplantation and other intraocular surgical operations. Previous work in this field has been directed to protecting corneas with both non-biological and biological polymers.
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Web site: http://www.delphion.com/details?pn=US06051560__ •
Composition containing readily absorbable calcium and process for producing the same Inventor(s): Katsukura; Shinya (Tokyo, JP) Assignee(s): Nishimura; Masahiko (JP) Patent Number: 6,203,827 Date filed: November 25, 1997 Abstract: A composition containing readily absorbable calcium which comprises a calcium salt and 0.2 to 5% by weight of chondroitin sulfate based on the calcium content in the calcium salt. A calcium salt preferably used in this composition is obtained by, for example, baking external skeletons of sea urchins in an oven to thereby give calcium oxide, hydrating it into calcium hydroxide and then reacting it with an organic carboxylic acid to thereby give a calcium salt. The absorption of calcium in vivo is highly promoted by adding chondroitin sulfate. As a calcium source various natural and synthetic calcium can be used. Excerpt(s): This invention relates to a composition containing readily absorbable calcium and to a process for producing the same. Calcium is one of constituent ingredients of bones and teeth, and it is of importance as a factor regulating muscles, nervous systems and hormone secretion for maintaining functions of a living body. Furthermore it has been proved that it affects immunological functions. Though it is known that lack of calcium ingestion affects development of bone diseases, as well as adult diseases such as hypertension, ischemic heart diseases and endocrine diseases and calcium has been becoming of general interest, the amount thereof ingested in the food life is not yet sufficient in our country. Therefore, various calcium preparations and health foods containing calcium have been proposed and sold on the market for making up the deficiency. For example, chemically synthesized calcium compounds, calcium compounds originating in shellfishes, crustaceans, eggshells and animals' bones, and calcium originating in plants such as seaweeds have been used so far, but the absorption in vivo of such calcium is not so high and in many cases where they are used as preparations or food additives, they have difficulties in their taste and flavor, so that they have not yet been in popular use. Web site: http://www.delphion.com/details?pn=US06203827__
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Concentration of glycosaminoglycans and precursors thereto in food products Inventor(s): Marino; Richard P. (646 Margo Ave., Long Beach, CA 90803) Assignee(s): none reported Patent Number: 5,922,692 Date filed: March 11, 1998 Abstract: Accordingly, a method is provided for concentrating precursors to vertebrate connective tissue in foodstuffs to be ingested by humans and pets as part of their daily sustenance. The present method comprises the following steps: (a) providing raw vertebrate connective tissue; (b) disintegrating the raw vertebrate connective tissue into an aggregation of particles having a substantially homogenous particle size, preferably
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via an emulsification process, thereby forming liquefied connective tissue; and (c) thermally processing the liquefied connective tissue, resulting in a readily-edible foodstuff rich in chondroitin sulfates, glucosamine, and other connective tissue building blocks. Also provided herein are foodstuffs resulting from the method as well as foodstuffs comprising vertebrate connective tissue and at least one carrier substrate selected from the group consisting of farinaceous and proteinaceous carriers, with the foodstuffs having chondroitin sulfate and glucosamine concentrations of at least about 0.5 wt % and 0.3 wt %, respectively. Finally, a method of administering precursors to connective tissue is provided herein, comprising providing a foodstuff made from the above-described novel process steps, or having the above-described novel composition, and serving it to a human or pet, thereby representing both daily sustenance and an efficient way to consume therapeutic amounts of chondroitin sulfates, glucosamine, and other building blocks of connective tissue without the need to take pills or tablets. Excerpt(s): The present invention relates generally to the nutritional use of vertebrate connective tissue, and more particularly, to the concentration of glycosaminoglycans and precursors thereto from vertebrate connective tissue, such as bovine cartilage and connective tissues, in food products to be consumed by humans or pets for daily sustenance. The connective tissue of vertebrates includes bone and cartilage as well as tissue that underlies the skin, envelops muscle, and occupies space between internal organs. The primary building blocks of connective tissue are proteoglycans (PG), which are linked to collagen fibers to form connective tissue. Proteoglycan subunits are comprised of glycoaminoglycans (also known as GAGs or mucopolysaccharides) attached in large numbers to a core protein, with these proteoglycan subunits being attached to a very long hyaluronic acid molecule via protein links to form aggregating proteoglycan. GAGs are long-chain polymers with monomer units comprising an aminosugar and an organic acid or sugar. One type of GAG is chondroitin sulfate, which is composed of glucuronic acid and N-acetyl galactosamine sulfate. Glucosamine is a key precursor to both GAGs and hyaluronic acid molecules, which are the primary components of PGs, as discussed above. In fact, the bioavailability of glucosamine is the rate-limiting step in the synthesis of GAGs and PGs. Connective tissue serves to maintain the structure of the body parts in relation to one another and to cushion the interfaces between bones, among many other purposes. Normal, healthy connective tissue is resilient, compressive, and possessive of a "slippery" type surface, while diseased or damaged connective tissue is rough and brittle. Damage to connective tissue serving to cushion bone interfaces and ease skeletal movement (such as at the knee joint) may actually result in the bones grinding against one another during movement, causing considerable pain and even constraint of movement. Damage to, or disease of, the various types of connective tissues can lead to a variety of adverse effects for humans and pets. Web site: http://www.delphion.com/details?pn=US05922692__ •
Dietary regimen of nutritional supplements for relief of symptoms of arthritis Inventor(s): Florio; Vito V. (Tamarac, FL) Assignee(s): Omni Nutraceuticals, Inc (Los Angeles, CA) Patent Number: 6,136,795 Date filed: November 18, 1998 Abstract: This invention is directed to a dietary regimen and a unique combination of nutritional supplements and a method. More specifically, this invention is directed to a
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unique combination of nutritional supplements which provides symptomatic relief from arthritis. The unique combination of nutritional supplements of this invention is believed to function by both increasing the available (effective blood level) of antiinflammatory agents and promotion of the healing/regenerative process in the effected joints, thus, producing unexpected and lasting symptomatic relief from the debilitating effects of both osteoarthritis and rheumatoid arthritis. The essential nutritional supplements of the dietary regimen of this invention are as follows:(a) gamma linolenic acid (unrefined), hereinafter "GLA"(b) a mixture of eicosapentaenoic acid and docosahexaneoic acid, hereinafter collectively "EPA"(c) a mixture of chondroitin sulfate, N-acetyl glucosamine sulfate, glucosamine sulfate and manganese aspartate, hereinafter collectively "CHONDROX"The regimen is adjusted based upon the weight of the individual, and once symptomatic relief is achieved, the individual remains essentially free from the debilitating effects of arthritis so as long the daily regimen is faithfully followed. Excerpt(s): This invention is directed to a unique combination of nutritional supplements and a method. More specifically, this invention is directed to a unique combination of nutritional supplements which provides symptomatic relief from arthritis. The unique combination of nutritional supplements of this invention is believed to function by increasing the available (effective blood level) of antiinflammatory agents and, thus, unexpected and lasting symptomatic relief from the debilitating effects of both osteoarthritis and rheumatoid arthritis. Osteoarthritis or degenerative joint disease is the most common form of arthritis. It is seen primarily, but not exclusively, in the elderly; surveys have indicated that 80% of persons over the age of 50 have osteoarthritis. Under the age of 45, osteoarthritis is much more common in men; after age 45 it is ten times more common in women than men. The weight-bearing joints and joints of the hands are the joints principally affected by the degenerative changes associated with osteoarthritis. Specifically, there is much cartilage destruction, followed by hardening, and the formation of large bone spurs (Calcified osteophytes) in the joint margins. Pain, deformity and limitation of motion in the joint results. Inflammation is usually minimal. Web site: http://www.delphion.com/details?pn=US06136795__ •
Guidewire having hydrophilic coating Inventor(s): Deem; Mark E. (San Francisco, CA) Assignee(s): Medtronic, Inc. (Minneapolis, MN) Patent Number: 6,042,876 Date filed: November 23, 1998 Abstract: A guidewire comprises a core wire having a coil tip at its distal end. The coil tip includes a helically wound filament having adjacent turns spaced apart by a preselected distance. The guidewire is coated with a polymeric material, typically a hydrophilic polysaccharide, such as hyaluronic acid or chondroitin sulfate. By properly selecting the spacing between adjacent turns of the coil tip, the hydrophilic coating will adhere to the coil tip in a manner which does not penetrate the coil and which does not significantly interfere with flexibility and bendability of the coil tip. Excerpt(s): The present invention relates generally to medical guidewires. More particularly, the present invention relates to guidewires having hydrophilic coatings and methods for their fabrication. Medical guidewires are used in a variety of
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procedures for guiding catheters and other devices to target sites within a patient's body. Of particular interest to the present invention, intravascular guidewires are used for the percutaneous introduction and guiding of both diagnostic and therapeutic catheters within a patient's vasculature. Such intravascular guidewires typically comprise a core wire formed from stainless steel, nickel-titanium alloy, tantalum, or other metals, and a coil tip disposed over the distal end of the core wire. The coil tip is typically a helically wound filament composed of a malleable metal which can be shaped by the physician in order to facilitate placement within the vasculature. After an initial puncture or cut-down is provided into the femoral or other access artery, the guidewire is advanced to the target location by pushing from the proximal end. The guidewire can also be twisted from the proximal end to properly position the bent or deflected coil tip in order to steer the guidewire through arterial junctions. Guidewires have usually been coated with certain materials in order to facilitate placement through the vasculature. Initially, silicone, PTFE, and other lubricous (but non-hydrophilic) materials were applied both to the core wire and the coil tip in order to reduce friction between the guidewire and adjacent surfaces as the guidewire is introduced. Web site: http://www.delphion.com/details?pn=US06042876__ •
Herbal composition and method for combating inflammation Inventor(s): Blackner; Lori (Chattanooga, TN), Charters; Alec (Salt Lake City, UT), Morris; Shayne (Ogden, UT), Selander; James (Park City, UT), Thompson; Robert Charles (Peterson, UT) Assignee(s): Nutraceutical Corporation (Park City, UT) Patent Number: 6,541,045 Date filed: January 4, 2002 Abstract: An herbal composition for combating inflammation, comprising therapeutically effective amounts of Japanese knotweed, Devil's claw, grapeskin, and syzygium is provided. Also provided is an herbal composition for treating a cough and/or common cold, comprising therapeutically effective amounts of Japanese knotweed, lobelia, echinacea, slippery elm, Devil's claw, adhatoda, vitamin C, grapeskin, and syzygium. An herbal composition for alleviating menstrual discomfort, comprising therapeutically effective amounts of Japanese knotweed, chaste tree berry, Mexican wild yam, dandelion, Devil's claw, grapeskin, and syzygium is provided. Also provided is an herbal composition for soothing muscles and joints, comprising therapeutically effective amounts of Japanese knotweed, N-acetyl D-glucosamine, chondroitin sulfate, D-glucosamine hydrochloride, methylsulfonylmethane, grapeskin, syzygium, and Devil's claw. Methods of using the herbal compositions are also provided. Excerpt(s): The present invention relates generally to herbal compositions and methods for combating inflammation. Arthritic disorders, including rheumatism, osteoarthritis, dysplasia, lupus, bursitis, and gout, are all characterized by inflammation and pain in bones, joints, muscles, and related connective tissues. Most of the forms are progressive. Those who suffer from inflammation experience pain and discomfort and may, in advanced cases, lose the effective use of inflamed joints. Thus, the goal of therapeutic methods for treating bone or joint inflammation is the relief of pain and discomfort and the restoration of use of inflamed joints. Certain enzymes play a role in causing inflammation. One of the features of inflammation is increased oxygenation of arachidonic acid, which is metabolized by two enzymic pathways--the cyclooxygenase
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(CO) and the 5-lipoxygenase (5-LO) pathways--leading to the production of prostaglandins and leukotrienes, respectively. Prostaglandins and leukotrienes are mediators of inflammation. Therapies designed to inhibit cyclooxygenase and/or lipoxygenase activity are therefore of great interest. Web site: http://www.delphion.com/details?pn=US06541045__ •
Human gene encoding human chondroitin 6-sulfotransferase Inventor(s): Tabas; Ira (New City, NY), Williams; Kevin Jon (Wynnewood, PA) Assignee(s): Thomas Jefferson University (Philadelphia, PA) Patent Number: 6,399,358 Date filed: January 29, 1998 Abstract: Genes and polypeptides encoded thereby of human chondroitin 6sulfotransferase are provided. Vectors and host cells comprising these genes and transgenic animals capable of expressing them are also provided. In addition, methods of identifying polymorphic chondroitin 6-sulfotransferase in humans and activators or inhibitors of this enzyme are provided. Excerpt(s): Chondroitin sulfate is an important component of the extracellular matrix of animals. Chondroitin 6-sulfate (C6S), the form that is sulfated at position 6 of its Nacetylgalactosamine residues, has been implicated in several key roles in human biology, including development (Toledo et al. Am. J. Med. Gen. 1978, 2:385-395; Mourao et al, Biochem. Biophys. Res. Commun. 1981, 98:388-396; Habuchi et al. J. Biol. Chem. 1986, 261:1031-1040), cancer (Adany et al. J. Biol. Chem. 1990, 265:11389-11396), and atherosclerosis (Williams, K. J. and Tabas, I. Arterioscl. Thromb. Vasc. Biol. 1995, 15:551561). The abundance of C6S is under genetic (Edwards, I. J. and Wagner, W. D. J. Biol. Chem. 1988, 263:9612-9620) and stimulatory (Schonherr et al. J. Biol. Chem. 1991, 266:17640-17647) control. Fukata et al. recently cloned the chick cDNA encoding C6ST, the essential enzyme in C6S synthesis (J. Biol. Chem. 1995, 270:18575-18580). A human genomic DNA encoding C6ST has now been cloned and sequenced. An object of the present invention is to provide a gene encoding human chondroitin 6-sulfotransferase. Web site: http://www.delphion.com/details?pn=US06399358__
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Inhibition of complement pathway by sea cucumber fractions Inventor(s): Collin; Peter Donald (Sunset, ME) Assignee(s): Coastside Bio Resources (Stonington, ME) Patent Number: 5,989,592 Date filed: October 3, 1997 Abstract: The present invention relates to methods for inhibiting the complement pathway in a mammal comprising administering an effective dose of a composition comprising an active ingredient selected from the group consisting of isolated sea cucumber (Phylum Echinodermata, Class Holothuroidea) body wall, isolated sea cucumber epithelial layer, isolated sea cucumber flower, sea cucumber fucosylated chondroitin sulfate, combinations thereof, active derivatives thereof or combinations of active derivatives thereof.
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Excerpt(s): 5. combinations thereof. The complement system is a group of proteins that constitutes about 10 percent of the globulins in the normal serum of humans (Hood, L.E. et al 1984, Immunology, 2nd Edition, The Benjamin/Cummings Publishing Co., Menlo Park, Calif. p. 339). Complement plays an important role in the mediation of immune and allergic reactions (Rapp, H. J. and Boros, T., 1970, Molecular Basis of Complement Action, Appleton-Century-Crofts Meredith, N.Y.). The complement system identifies foreign or damaged cells and tissue by covalently attaching a chemotactic protein (C3) which is recognized by host cell receptors. Complement is normally tightly regulated through the presence of complement inhibitors and the short half-life and substrate specificity of the enzymes involved in the activation cascade. There are three major pathways of complement activation. First, the "classical pathway," which is activated by antibody/antigen binding. Second, the newly recognized "collecting pathway," activated by the binding of "mannose binding protein" to a complex carbohydrate, thereby activating a specific enzyme called "mannose binding protein activated serine proteinase" (MASP) that in turn activates another proteinase that generates chemotactic peptides such as C3. Third, the "alternative pathway," which is activated by the presence of a specific substrate called C3bB, a complex of complement proteins. The alternative pathway is controlled by the availability of the substrate C3bB. (Fearon & Austen, "Activation of the alternative complement pathway with rabbit erythrocytes by circumvention of the regulatory action of endogenous control proteins," Journal of Experimental Medicine, vol. 146, pp. 22-33 (1977); Pangburn, et al., "Localization of the heparin-binding site on complement factor H," Journal of Biological Chemistry, vol. 266, pp. 16847-53 (1991)). Web site: http://www.delphion.com/details?pn=US05989592__ •
Keratan sulfate 6-sulfotransferase and DNA coding for the same Inventor(s): Fukuta; Masakazu (Mie-ken, JP), Habuchi; Osami (Nagoya, JP) Assignee(s): Seikagaku Kogyo Kabushiki Kaish (Tokyo, JP) Patent Number: 6,051,406 Date filed: December 1, 1997 Abstract: A polypeptide of keratan sulfate 6-sulfotransferase having the following physicochemical properties:1 action: a sulfate group is transferred from a sulfate group donor to the hydroxyl group at C-6 position of galactose residue of keratan sulfate;2 substrate specificity: a sulfate group is not substantially transferred to chondroitin, chondroitin sulfate A, chondroitin sulfate C, dermatan sulfate and CDSNS-heparin;3 optimum pH: 6.2 to 6.54 activation: an activity is increased by Mn.sup.2+ or Ca.sup.2+;5 Km value for 3'-phosphoadenosine 5'-phosphosulfate: about 2.times.10.sup.-7 M; anda DNA coding for the polypeptide. Excerpt(s): The present invention relates to a polypeptide of glycosaminoglycan sulfotransferase (glycosaminoglycan sulfate group transferase) and a DNA coding for it. More particularly, the present invention relates to a polypeptide of 6-sulfotransferase originating from human, which sulfates keratan sulfate, but substantially does not sulfate chondroitin, chondroitin sulfate A, chondroitin sulfate C, dermatan sulfate and CDSNS-heparin, and a DNA coding for it. The present invention further relates to a method for the preparation of the polypeptide and a method for using the polypeptide of 6-sulfotransferase. Keratan sulfate is a kind of glycosaminoglycan constituted by galactose residues (Gal), and N-acetylglucosamine residues (GlcNAc) a part of which has substituents of sulfate groups at the C-6 position, and its repetition structure is
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represented by 3Gal.beta.1.fwdarw.4GlcNAc.beta.1.fwdarw. It is expected that, if a gene for sulfotransferase for glycosaminoglycan could be cloned, it would provide information about substrate specificity of its receptors and approaches useful for structural and functional investigation of glycosaminoglycan. Various glycosaminoglycan sulfotransferases seem to be involved in the synthesis of glycosaminoglycan. However, it is difficult to clone a cDNA of sulfotransferase. Web site: http://www.delphion.com/details?pn=US06051406__ •
Method for accelerating clearance of hemorrhagic blood from the vitreous body with hyaluronidase Inventor(s): Carpio Aragon; Gabriel Arturo (Tijuana, MX), Gutierrez Flores; Jose Luis (Tijuana, MX), Karageozian; Hampar L. (San Juan Capistrano, CA), Karageozian; Vicken H. (San Juan Capistrano, CA), Kenney; Maria Cristina (Malibu, CA), Nesburn; Anthony B. (Malibu, CA) Assignee(s): Advanced Corneal Systems (Irvine, CA) Patent Number: 6,039,943 Date filed: August 24, 1998 Abstract: A thimerosal-free hyaluronidase is prepared wherein the preferred hyaluronidase is devoid of molecular weight fractions below 40,000 MW, between 6070,000 MW and above 100,000 MW. Also a method for accelerating the clearance of hemorrhagic blood from the vitreous humor of the eye is carried out by contacting at least one hemorrhage-clearing enzyme (e.g., hyaluronidase,.beta.-glucuronidase, matrix metalloproteinase, chondroitinase, chondroitin sulfatase or protein kinase) with the vitreous humor in an amount which is effective to cause accelerated clearance of blood therefrom. Excerpt(s): The present invention relates generally to enzyme preparations for therapeutic administration to the eyes of humans or other mammals, and more particularly to a) a method for utilizing one or more enzymes to accelerate the rate at which hemorrhagic blood is cleared from the vitreous body of the mammalian eye and b) an improved hyaluronidase preparation for ophthalmic administration. In human beings, the anatomy of the eye includes a "vitreous body" which occupies approximately four fifths of the cavity of the eyeball, behind the lens. The vitreous body is formed of gelatinous material, known as the vitreous humor. Typically, the vitreous humor of a normal human eye contains approximately 99% water along with 1% macromolecules including; collagen, hyaluronic acid, soluble glycoproteins, sugars and other low molecular weight metabolites. The retina is essentially a layer of nervous tissue formed on the inner posterior surface of the eyeball. The retina is surrounded by a layer of cells known as the choroid layer. The retina may be divided into a) an optic portion which participates in the visual mechanism, and b) a non-optic portion which does not participate in the visual mechanism. The optic portion of the retina contains the rods and cones, which are the effectual organs of vision. A number of arteries and veins enter the retina at its center, and splay outwardly to provide blood circulation to the retina. Web site: http://www.delphion.com/details?pn=US06039943__
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Method for processing fish heads and apparatus for separating processed fish heads Inventor(s): Fujii; Keisuke (Nemuro, JP) Assignee(s): Fujii Suisan Co., Ltd. (Hokkaido, JP) Patent Number: 6,347,986 Date filed: August 16, 2000 Abstract: A fish head, after being heated and softened, is broken down into its nose cartilage and various residues by being rotated and crushed, after a fish head. The method of processing a fish head also includes the following steps: separating the nose cartilage into an end proboscis part and a rear part; making a paste by removing fats after making comminutions of the cartilage; making a paste by removing the fats after making comminutions of the end proboscis part; making a paste of the aforesaid rear part; making a raw material from which to extract chondroitin sulfate, after removing the fats of the nose cartilage; making a powder from the paste of the end proboscis part; and making a powder from the paste of the rear part. Through the above methods it is possible to break down a fish head into its various parts easily and accurately; in particular, to separate the nose cartilage from the rest of the fish head, to break down the nose cartilage into the end proboscis part and the rear part, and to make the above parts, including the residues, into products having forms that are easy to handle and utilize. Excerpt(s): This invention is intended to serve as an apparatus that utilizes a method of processing fish heads and separating them into their various parts, thus making possible the effective use of fish heads, which generally are treated as fish-processing waste. In recent years, the aquaculture of fish, especially salmonids, has been increasing greatly, and it is said that more than 200,000tons of chum salmon are produced in Japan each year. However, the consumption of so-called salted salmon with the head intact is decreasing in Japan, as the eating habits in this country change. In contrast, the production of flaked food, dried dainty salmon without the head, and thickly sliced fish fillet is increasing remarkably. In producing these foods, the fish head is cut off by a machine and almost all of the heads are disposed of as fish-processing waste. The disposal of such waste is becoming a social problem, and it is anticipated that the volume of such so-called waste will increase in the future. However, the cartilage that is in the head of fish in the Chondrichthyes class, such as sharks, is well-known for being sold as a health food after it is processed into a fine powder. But it is becoming difficult to acquire the cartilage of sharks, because this shark resource itself is rare, in addition to being extremely expensive. Also, special international regulations and other factors pose additional problems. Therefore, at present, there is much interest in effectively using the nose cartilage of fish of the Osteichthyes class, such as salmonids, as a substitute for shark cartilage, which is expensive and difficult to obtain. Web site: http://www.delphion.com/details?pn=US06347986__
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Method for supplementing the diet Inventor(s): Deffner; Kathleen (Taylorsville, UT), Rosenberg; Thomas D. (Salt Lake City, UT) Assignee(s): Nutriex, L.L.C. (Salt Lake City, UT) Patent Number: 6,579,544 Date filed: May 31, 2000
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Abstract: A dietary supplement blend composition is disclosed, the basic formulation of the composition containing vitamins, minerals, and carotenoids. The composition can also contain bioflavonoids, cartilage protectors such as glucosamine or chondroitin,.alpha.-lipoic acid, coenzyme Q10, and a source of omega-3 fatty acids such as flax seed oil. The composition is beneficial for improving health and preventing disease, particularly for degenerative conditions. A method for supplementing the diet is also disclosed, wherein the quantity of daily rations of the dietary supplement blend composition is determined based on the person's age, body weight, and quality of diet. Excerpt(s): Not Applicable. This invention relates to dietary supplements. More particularly, the invention relates to compositions and methods for supplementing the diet for improving health and preventing disease. Web site: http://www.delphion.com/details?pn=US06579544__ •
Method for the preparation of chondroitin sulfate compounds Inventor(s): Ikegami; Toru (Tosu, JP), Ohba; Hideki (Kitakyushu, JP), Park; Sung Soo (Tosu, JP), Sakaki; Tsuyoshi (Tosu, JP), Sallay; Imre (Tosu, JP), Shibata; Masao (Ogoori, JP), Sumi; Toshihisa (Tosu, JP) Assignee(s): Japan as represented by Secretary of Agency of Industrial Science and (Tokyo-to, JP) Patent Number: 6,342,367 Date filed: February 25, 2000 Abstract: Disclosed is an economical method for the preparation of chondroitin sulfates A and C useful as an effective ingredient of medicaments from fish scales as a waste material discharged from fishery in large quantities. Fish scales are enzymatically decomposed in an aqueous medium in the presence of a protease to isolate the chondroitin sulfate compounds and by-product polypeptides followed by removal of the by-product polypeptides from the aqueous solution by a cation-exchange treatment and then the aqueous solution of the chondroitin sulfate compounds is subjected to fractional precipitation by the addition of ethyl alcohol as the precipitant. Excerpt(s): The present invention relates to a novel and economical method for the preparation of chondroitin sulfate compounds. More particularly, the invention relates to a method for the preparation of chondroitin sulfate compounds including chondroitin sulfate A and chondroitin sulfate C having usefulness as an effective ingredient in eye lotions and therapeutic medicaments for neuralgia and arthralgia by using an inexpensive raw material available in large quantities. which can be classified into several types depending on the combinations and bonding positions of the substituents R.sup.1 to R.sup.4 including chondroitin sulfate A when R.sup.1 is SO.sub.3 H and R.sup.2, R.sup.3 and R.sup.4 are each a hydrogen atom, i.e. chondroitin4-sulfate, chondroitin sulfate C when R.sup.2 is SOH and R.sup.1, R.sup.3 and R.sup.4 are each a hydrogen atom, i.e. chondroitin-6 sulfate, chondroitin sulfate D when R.sup.2 and R.sup.3 are each SO.sub.3 H and R.sup.1 and R.sup.4 are each a hydrogen atom, chondroitin sulfate E when R.sup.1 and R.sup.2 are each SO.sub.3 H and R.sup.3 and R.sup.4 are each a hydrogen atom, chondroitin sulfate K when R.sup.1 and R.sup.4 are each SO.sub.3 H and R.sup.2 and R.sup.3 are each a hydrogen atom and chondroitin sulfate B, i.e. dermatan sulfate, when most of the D-glucuronic acids are 5-epimerized into L-iduronic acid of which R.sup.1 is a sulfate group. Among these chondroitin sulfate compounds, chondroitin sulfate A is prepared mainly from notochords of
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sturgeons or nasal cartilages of whales and chondroitin sulfate C is prepared mainly from cartilages of sharks as the respective starting raw materials. Availability of these raw materials, however, is limited and, in addition, the procedure for the preparation of the chondroitin sulfate compounds from these materials is relatively complicated not to be suitable for large-scale production of the products consequently with a high production cost. Web site: http://www.delphion.com/details?pn=US06342367__ •
Methods for treating arthritis using collagen type II, glucosamine chondroitin sulfate, and compositions Inventor(s): Nakamura; Robert M. (La Jolla, CA), Sorgente; Nino (San Clemente, CA) Assignee(s): Immudyne, Inc. (Houston, TX) Patent Number: 6,162,787 Date filed: April 2, 1999 Abstract: The invention describes compositions and methods for treatment of rheumatoid arthritis and osteoarthritis. The compositions comprise insoluble, native collagen Type II in a particular form in combinations with other active agents, including glucosamine, chondroitin, ascorbate, boron and magnesium. Also described are methods for producing particulated insoluble native collagen Type II. Excerpt(s): The present invention provides a method for the isolation and purification of insoluble, native collagen and chondroitin sulfate from cartilages, a therapeutic method and nutriceutical formulation containing therapeutic amounts of collagen Type II, glucosamine and/or chondroitin sulfate and/or magnesium ascorbic phosphate, and/or boron for the treatment of rheumatoid arthritis and osteoarthritis in humans and animals. The cartilage of the joints is called hyaline cartilage (from the Greek "hyalos" which means glass); hyaline cartilage is found not only on all surface of bones that move (articular cartilage) but also in the nose, larynx, ribs and trachea. This cartilage consists of 70% water, about 10% collagen Type II, and the rest is various protein and specialized complex sugars, called proteoglycans. The collagen and the proteoglycans form a meshwork that confers upon this cartilage stiffness, viscoelasticity, and durability. The articular cartilage provides load bearing, resilience, a low friction surface and distributes the load over the entire synovial joint. Even though the articular cartilage is very thin (about one eighth of an inch thick) it performs its function for the life of the individual (80-90 years or more) without any significant deterioration, unless it becomes injured or diseased. There are two major diseases that affect cartilage, namely osteoarthritis and rheumatoid arthritis; both osteoarthritis and rheumatoid arthritis result in degradation and degeneration of the articular cartilage. Osteoarthritis is a disease of cartilage only and does not have an immunological component. The major symptoms of osteoarthritis are pain, stiffness, crackling, and enlargement and deformities of the affected joints; at the early stage of osteoarthritis there is little inflammation and swelling of the joints, however in advanced stages swelling and inflammation is usually present. Rheumatoid arthritis is an autoimmune systemic disease accompanied by severe inflammation of the joints. In most patients rheumatoid arthritis begins with a general feeling of malaise, fatigue, often accompanied by diffuse musculoskeletal pain. Eventually the disease progresses resulting in pain on motion, tenderness, swelling and deformation of multiple joints; because rheumatoid arthritis is a systemic disease, it may be accompanied by extra-articular complications, such as anemia, vasculitis, scleritis, pleurisy, pericarditis, and peripheral neuritis.
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Modulators of polysaccharides and uses thereof Inventor(s): Mohamadzadeh; Mansour (Plano, TX), Mummert; Mark E. (Dallas, TX), Takashima; Akira (Coppel, TX) Assignee(s): The University of Texas System (Austin, TX) Patent Number: 6,653,285 Date filed: March 22, 2000 Abstract: The present invention provides peptides with a specific affinity for glycosaminoglycan molecules. These peptides may have any number of functions, including but not limited to use as inhibitors of glycosaminoglycan-mediated processes, enhancers of glycosaminoglycan-mediated processes, and as molecular probes to identify the presence of a specific glycosaminoglycan. Peptides of the invention may be directed against any glycosaminoglycan, including hyaluronic acid, chondroitin sulfate A, chondroitin sulfate C, dermatan sulfate, heparin, keratan sulfate, keratosulfate, chitin, chitosan 1, and chitosan 2. These isolated peptides may have therapeutic uses in the treatment or prevention of diseases involving infection, inflammatory diseases, cancer, infections, etc. The peptides may also have other biological functions such as contraception. Excerpt(s): The invention relates to peptide inhibitors of glycosaminoglycans. This invention also relates to formulations, uses and methods of identifying such inhibitors. The extracellular matrix (ECM) is a dynamic assemblage of interacting molecules that regulate cell functions and interactions in response to stimulation. One class of extracellular matrix macromolecules, the glycosaminoglycans, are molecules known to be involved in a wide array of both normal and abnormal biological processes, including cell migration, differentiation, proliferation, immune response and cytoskeletal organization. The glycosaminoglycan hyaluronan (HA) is a repeating disaccharide of [GlcNAc.beta.1-4GlcUA.beta.1-3].sub.n that exists in vivo as a high molecular weight linear polysaccharide. HA is found in mammals predominantly in connective tissues, skin, cartilage, and in synovial fluid, and is also the main constituent of the vitreous of the eye. In connective tissue, the water of hydration associated with HA creates spaces between tissues, thus creating an environment conducive to cell movement and proliferation. HA plays a key role in biological phenomena associated with cell motility including rapid development, regeneration, repair, embryogenesis, embryological development, wound healing, angiogenesis, and tumorigenesis (Toole, Cell Biol. Extracell. Matrix, Hay (ed), Plenum Press, New York, 1384-1386 (1991); Bertrand et al. Int. J. Cancer 52:1-6 (1992); Knudson et al, FASEB J. 7:1233-1241 (1993)). HA levels have been shown to correlate with tumor aggressiveness (Ozello et al., Cancer Res. 20:600-604 (1960); Takeuchi et al., Cancer Res. 36:2133-2139 (1976); Kimata et al., Cancer Res. 43:1347-1354 (1983)), and can be indicative of the invasive properties of tumor cells. M. M. Knupfer et al., Anticancer Res 18:353-6 (1998). Web site: http://www.delphion.com/details?pn=US06653285__
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Natural composition for treating bone or joint inflammation Inventor(s): Weisman; Bernard (17061 Windsor Park Ct., Boca Raton, FL 33496-1634) Assignee(s): none reported Patent Number: 5,888,514 Date filed: May 23, 1997 Abstract: A composition for treating a mammal having a condition characterized by bone or joint inflammation comprises:2,250 mg soluble bovine cartilage,250 mg soluble shark cartilage,1,000 mg glucosamine sulfate,350 mg mucopolysaccharide concentrate,225 mg proteolytic enzymes from hog pancreatic extract,500 mg standardized extract of ashwagandha,470 mg extract of Boswellia serrata comprising 150 mg boswellic acid1,000 mg chondroitin polysulfate,100 mg extract of sea cucumber,300 mg black currant seed oil,3,500 mg ascorbic acid (vitamin C),150 mg pyridoxine HCl (vitamin B6),1,000 mg devil's claw powder. Excerpt(s): This invention relates to a mixture of natural ingredients for the treatment of bone or joint inflammation. Bone and joint inflammation is a scourge of both animals and humans. Examples of this debilitating condition include arthritis, including rheumatoid arthritis, rheumatism, tendonitis, etc. Those who suffer from bone or joint inflammation experience pain and discomfort, and may, in advanced cases, lose the effective use of inflamed joints. The goal of therapeutic methods for treating bone or joint inflammation is the relief of pain and discomfort, and the restoration of use of inflamed joints. Web site: http://www.delphion.com/details?pn=US05888514__
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Oral and injectable nutritional composition Inventor(s): Petito; Anita M. (1890 Bucknell Dr., Bethlehem, PA 18015), Petito; George D. (1890 Bucknell Dr., Bethlehem, PA 18015) Assignee(s): none reported Patent Number: 6,476,005 Date filed: July 26, 1999 Abstract: An oral and injectable composition for mammals comprising a salt of glucosamine, such as glucosamine hydrochloride, sulfate, nitrate, or iodide, a chondroitin sulfate, hydrolyzed or native collagen, a sodium hyaluronate, chelated manganese ascorbate, and L-malic acid in powder form for oral ingestion or in a solution of sterilized water for injection. The composition acts as a chondroprotective agent which provides foundational support for the creation of new body tissue and cartilage growth in humans and animals. Other beneficial physiological properties include the enhancement of chondrocyte synthesis, the healing of chronic or acute wounds, the maintenance of healthy muscle and tissue, increasing the desirable concentration of hyaluronic acid, and anti-inflammatory activity. Excerpt(s): The present invention relates to an oral and injectable nutritional composition in powder or aqueous form for mammalian use comprising glucosamine or a glucosamine salt, chondroitin sulfate, hydrolyzed collagen, sodium hyaluronate, a manganese salt, and, optionally, L-malic acid. Phosphate salts are excluded from this nutritional composition. The related art of interest describes various oral and topical products for improving various physiological functions of the human body. The related
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art will be discussed in the order of perceived relevance to the present invention. U.S. Pat. No. 5,141,928 issued on Aug. 25, 1992, to Lawrence Goldman describes ophthalmic medications containing glycosaminoglycan polysulfates (GAGPS) or mucopolysaccharides having a molecular weight in the range of 5,000 to 20,000 Daltons combined with antibiotics for treating eye infections and antimicrobial agents such as pilocarpine or epinephrine for glaucoma. GAGPS include chondroitin sulfate and hyaluronic acid that contain hexosamines. The medicament composition is thus distinguishable from the present invention prohibiting sulfates for its reliance on glycosaminoglycan polysulfates, antibiotics, and antimicrobial agents, which composition is limited to human use. Web site: http://www.delphion.com/details?pn=US06476005__ •
Peritoneal dialysis solutions and methods usable to minimize the injury and adverse physiological effects caused by peritonitis Inventor(s): Breborowicz; Andrzej (Posnan, PL), Oreopoulos; Dimitrios G. (Etobicoke, CA) Assignee(s): Baxter International Inc. (Deerfield, IL) Patent Number: 5,955,450 Date filed: August 16, 1996 Abstract: Peritoneal dialysis solutions are specially formulated for use during and immediately after an episode of peritonitis. The solutions include one or more additives to minimize the injury and physiological effects that peritonitis can cause. One additive is a mixture of amino acids sufficient to maintain a positive nitrogen balance, at least one of the amino acids being present in a dipeptide form. Another additive is a compound that scavenges free radicals generated by peritoneal macrophages activated by the peritonitis. Another additive is chondroitin sulfate that changes the permeability of the peritoneal membrane during subsequent dialysis using solutions free of chondroitin sulfate. Another additive is the degradation products of hyaluronic acid to enhance the regeneration of the peritoneal mesothelium without fibrosis. Excerpt(s): The invention generally relates to peritoneal dialysis solutions, especially those used in the practice of continuous ambulatory peritoneal dialysis, or CAPD. Peritoneal dialysis periodically infuses sterile aqueous solution into the peritoneal cavity. Diffusion exchange takes place between the solution and the bloodstream across the natural body membranes. The diffusion removes the waste products that the kidneys normally excrete. The waste products typically consist of solutes like sodium and chloride ions, and the other compounds normally excreted through the kidneys like as urea, creatinine, and water. The diffusion of water across the peritoneal membrane during dialysis is called ultrafiltration. The inflammation of the peritoneum, called peritonitis, is an undesired complication of peritoneal dialysis. The inflammation may lead to loss of mesothelial cells and the excessive growth of fibrous connective tissue in the peritoneum membrane, called fibrosis. These reactions can lead to the loss of ultrafiltration during dialysis. Web site: http://www.delphion.com/details?pn=US05955450__
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Pharmaceutical compositions and methods for improving wrinkles and other skin conditions Inventor(s): Murad; Howard (4316 Marina City Dr., Marina del Rey, CA 90292) Assignee(s): none reported Patent Number: 5,972,999 Date filed: September 3, 1998 Abstract: This application relates to a pharmaceutical composition for the prevention and treatment of skin conditions in a patient having a sugar compound that is converted to a glycosaminoglycan in the patient in an amount sufficient to thicken the skin, a primary antioxidant component in an amount sufficient to substantially inhibit the formation of collagenase and elastase, at least one amino acid component in an amount sufficient to assist in the thickening of the skin, and at least one transition metal component in an amount effective to bind collagen and elastic fibers and rebuild skin. In one preferred form, the composition further includes a catechin-based preparation, a glucosamine or a pharmaceutically acceptable salt or ester thereof, and a chondroitin or a pharmaceutically acceptable salt or ester thereof. In a more preferred form, the invention further includes a vitamin E source, a cysteine source, a vitamin B.sub.3 source, quercetin dihydrate, pyridoxal 5 phosphate-Co B.sub.6, a methionine source, and a vitamin A source. The invention further relates to a method for the prevention or treatment of skin conditions by administering the pharmaceutical composition in an amount therapeutically effective to modify the thickness of the skin to prevent or treat at least one skin condition. Excerpt(s): This application relates to pharmaceutical compositions, as well as methods, to supplement collagen and elastic tissues and thicken the dermis for the treatment of wrinkles and other skin conditions. Human skin is a composite material of the epidermis and the dermis. The topmost part of the epidermis is the stratum corneum. This layer is the stiffest layer of the skin, as well as the one most affected by the surrounding environment. Below the stratum corneum is the internal portion of the epidermis. Below the epidermis, the topmost layer of the dermis is the papillary dermis, which is made of relatively loose connective tissues that define the micro-relief of the skin. The reticular dermis, disposed beneath the papillary dermis, is tight, connective tissue that is spatially organized. The reticular dermis is also associated with coarse wrinkles. At the bottom of the dermis lies the subcutaneous layer. The principal functions of the skin include protection, excretion, secretion, absorption, thermoregulation, pigmentogenesis, accumulation, sensory perception, and regulation of immunological processes. These functions are detrimentally affected by the structural changes in the skin due to aging and excessive sun exposure. The physiological changes associated with skin aging include impairment of the barrier function and decreased turnover of epidermal cells, for example. [Cerimele, D., et al., Br. J. Dermatol., 122 Suppl. 35, p. 13-20 (April 1990)]. Web site: http://www.delphion.com/details?pn=US05972999__
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Pharmaceutical compositions containing chondroitinase and uses therefor Inventor(s): Bhaskar; K. Ramakrishnan (95 Burlington St., Lexington, MA 02420), Green; Allan M. (19 Francis Ave., Cambridge, MA 02138), Lamont; J. Thomas (390 Waltham St., Newton, MA 02465) Assignee(s): none reported Patent Number: 6,200,564 Date filed: April 10, 1998 Abstract: Gastrointestinal mucus from patients suffering from cystic fibrosis has been found to contain large amounts of chondroitin sulfate polymer. This finding indicates that the enzyme chondroitinase is useful for preventing gastrointestinal mucus from accumulating in cystic fibrosis patients, and subjects suffering from other diseases or conditions characterized by excess mucus secretion. Excerpt(s): Cystic fibrosis (CF) is a common lethal genetic disorder affecting approximately 1 in 2000 Caucasians.sup.1. The major pathological manifestations in CF are obstruction of pulmonary, gastrointestinal and pancreatobiliary ducts by accumulation of mucoid secretions ultimately leading to organ failure, particularly in the lung. The basic cellular defect in CF is abnormal chloride transport due to mutation of the cystic fibrosis transmembrane conductance regulator (CFTR) gene.sup.2-7. The CFTR gene encodes a protein required for the normal function of a cAMP regulated chloride channel present in secretory and other cells throughout the body. Despite rapid advances in our knowledge of the structure and function of CFTR, the cellular and physiological basis of the mucus abnormalities in CF remain obscure. Liver disease is the second leading cause of death in CF, after lung disease.sup.8,9. The major hepatic manifestation of CF is a distinct form of focal biliary cirrhosis, a condition that may be accompanied or preceded by inspissated cosinophilic material resembling the mucoid material found in other organs of CF patients.sup.10. Approximately 20% of surviving adolescents and adults with CF have morphologic evidence of liver disease, and about 10 to 15% of these develop complications of fibrosis, cirrhosis and portal hypertension requiring transplantation.sup.11. Other manifestations of biliary tract disease in CF include biliary sludge and casts, increased incidence of gallstones and common bile duct strictures. Very little is known of the pathogenesis of hepatobiliary disease in CF, and detailed analysis of the inspissated material plugging bile ductules has not been published. The abnormalities in biliary secretion are assumed to be related to the known single gene defect in CF, mutation of the CFTR. Recent studies by Cohen et al.sup.12 have documented that CFTR is localized in liver exclusively to the apical membrane of bile duct cells, but not in hepatocytes. This suggests that the hepatobiliary abnormalities in CF, particularly focal biliary cirrhosis, originate in bile duct cells, possibly by dysregulation of glycoprotein synthesis. The availability of immortalized human intrahepatic biliary epithelial cells from normal and CF patients allow direct comparison of synthesis and secretion of biliary macromolecules in vitro. Web site: http://www.delphion.com/details?pn=US06200564__
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Polypeptide-polymer conjugates active in wound healing Inventor(s): Petrica; Marianne P. (San Diego, CA), Pierschbacher; Michael D. (San Diego, CA), Polarek; James W. (Del Mar, CA), Ruoslahti; Erkki I. (Rancho Santa Fe, CA) Assignee(s): La Jolla Cancer Research Foundation (La Jolla, CA) Patent Number: 5,955,578 Date filed: June 5, 1995 Abstract: A conjugate of a synthetic polypeptide containing RGD or (dR) GD and a biodegradable polymer, such as hyaluronic acid or chondroitin sulfate is disclosed. Methods of making the conjugate and using it to aid wound healing by providing a temporary matrix are disclosed. Excerpt(s): The present invention relates to peptides conjugated to biodegradable polymers and methods for using the conjugates to promote the healing of wounds in mammals, including humans. The slow healing or lack of healing of both dermal wounds, such as decubitus ulcers, severe burns and diabetic ulcers and eye lesions, such as a dry eye and corneal ulcer, is a serious medical problem, affecting millions of individuals and causing severe pain or death in may patients. Even the healing of surgical wounds is a problem, particularly in aging and diabetic individuals. Although wounds may be quite dissimilar in terms of cause, morphology and tissue affected, they share a common healing mechanism. Each repair process ultimately requires that the correct type of cell migrate into the wound in sufficient numbers to have an effect: macrophages to debride wounds, fibroblasts for the formation of new collagen and other extracellular matrix components in wounds where the extracellular matrix was damaged, capillary endothelial cells to provide the blood supply, and epithelial cells to ultimately cover the wound. The unwounded dermis owes much of its structure and strength to the interactions of cells with the extracellular matrix. This matrix contains several proteins known to support the attachment of a wide variety of cells. These proteins include fibronectin, vitronectin, thrombospondin, collagens, and laminin. Although fibronectin is found at relatively low concentrations in unwounded skin, plasma fibronectin deposition occurs soon after wounding. When tissue is damaged, the extracellular matrix must be replaced to provide a scaffold to support cell attachment and migration. Web site: http://www.delphion.com/details?pn=US05955578__
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Polypeptides of glycosaminoglycan sulfotransferase originating from human and DNA coding for the polypeptides Inventor(s): Fukuta; Masakazu (Mie-ken, JP), Habuchi; Osami (Nagoya, JP) Assignee(s): Seikagaku Kogyo Kabushiki Kaisha (Tokyo, JP) Patent Number: 5,910,581 Date filed: July 24, 1997 Abstract: A polypeptide of glycosaminoglycan sulfotransferase originating from human and having the following physical and chemical properties:(i) action: sulfate group is transferred from a sulfate group donor to N-acetylgalactosamine residue or galactose residue of glycosaminoglycan;(ii) substrate specificity: sulfate group is transferred to the hydroxyl group position at C-6 of N-acetylgalactosamine residue of chondroitin; and
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sulfate group is transferred to the hydroxyl group position at C-6 of galactose residue of keratan sulfate; and(iii) molecular weight: about from 50,000 to 55,000 Da. Excerpt(s): The present invention relates to a polypeptide of glycosaminoglycan sulfotransferase originating from human and a DNA coding for the polypeptide. Chondroitin sulfate is a representative sulfated mucopolysaccharide (glycosaminoglycan). Chondroitin sulfate proteoglycan (CSPG) exists abundantly in cartilage, and is considered to participate in expression and maintenance of the phenotype of chondrocyte (Tsukahara, T., Okamura, M., Suzuki, S., Iwata, H., Miura, T., and Kimata, K. (1991) J. Cell Sci. 100, 387-395). CSPG exists also in various tissues other than cartilage, and is considered to play an important role for intercellular interactions (Kjellen, L. and Lindahl, U. (1991) Annu. Rev. Biochem. 60, 443-475). Major chondroitin sulfate found in mammalian and avian tissues has sulfate groups at C-6 or C-4 positions of acetylgalactosamine residues. The following knowledge has been obtained for the ratio of 6-sulfation/4-sulfation. (i) The ratio of chondroitin 6-sulfate/chondroitin 4sulfate (6/4 ratio) increases along with progress of final differentiation of cartilage. (ii) The 6/4 ratio in CSPG decreases in skin of rat along with passage of days after the birth. (iii) When CSPG and dermatan sulfate proteoglycan (DSPG) present in arterial smooth muscle cells are compared between an atherosclerosis-resistant pigeon and an atherosclerosis-sensitive pigeon, the major component is chondroitin 4-sulfate in the former species, whereas the major component is chondroitin 6-sulfate in the latter species. (iv) When monocytic leukemia cells (Ml) are cultured under the culture condition successively changed to suit for cell proliferation, inhibition of high-density proliferation and induction of differentiation to macrophage, the 6/4 ratio in CSPG is decreasing as the condition is changed in the above-defined order, and almost only chondroitin 4-sulfate is produced under the final differentiation-inducing state. (v) As a result of comparison of human colon normal tissue with human colon tumor tissue, chondroitin 6-sulfate and chondroitin in PG are increased in the tumor tissue. (vi) When mouse osteoblast cells are compared before and after calcification, the 6/4 ratio of DSPG is decreased in the cells after calcification. (vii) When platelet derived growth factor (PDGF) is added to a culture medium of monkey arterial smooth muscle cells, the 6/4 ratio of versican-like CSPG is increased as compared with a control with no addition of PDGF (Glycobiology Series (I), "Diversified World of Saccharides", Kodansha, pp. 164, 166). Web site: http://www.delphion.com/details?pn=US05910581__ •
Proteoglycan compositions for treatment of cardiovascular inflammatory diseases Inventor(s): Theoharides; Theoharis C. (14 Parkman St., Brookline, MA 02446) Assignee(s): none reported Patent Number: 6,624,148 Date filed: December 27, 2002 Abstract: Compositions with synergistic anti-inflammatory effects in inflammatory diseases resulting from activation and consequent degranulation of mast cells and followed by secretion of inflammatory biomolecules from the activated mast cells, composed of a heavily sulfated, non-bovine proteoglycan such as shark cartilage chondroitin sulfate C, and one or more of a hexosamine sulfate such as D-glucosamine sulfate, a flavone such as quercetin, an unrefined olive kernel extract that increases absorption of these compositions in various routes of administration, S-
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adenosylmethionine, a histamine-1 receptor antagonist, a histamine-3 receptor agonist, an antagonist of the actions of CRH, caffeine, and a polyamine. Excerpt(s): The invention is generally related to the treatment of inflammatory conditions. More specifically, the invention is related to compositions containing inhibitors of mast cell activation and secretion such as a proteoglycan that are designed to be used as dietary supplements or adjuvants to conventional approved medications for the relief of inflammatory conditions. There have been a number of mostly anecdotal reports that the proteoglycan chondroitin sulfate, as well as glucosamine sulfate, a product of the intestinal breakdown of proteoglycans, may be helpful in relieving the pain of osteoarthritis:--Shute N. Aching for an arthritis cure. US News and World Report, Feb. 10, 1997.--Cowley G. The arthritis cure? Newsweek, Feb. 17, 1997; Foreman J., People, and their pets, tout arthritis remedy. The Boston Globe, Apr. 7, 1997; Tye L. Treatment gains scientific attention. The Boston Globe, Sep. 25, 2000. A recent metaanalysis showed potential therapeutic benefit of chondroitin sulfate and/or glucosamine in osteoarthritis [McAlindon et al. J Am Med Assn. 283:1469 (2000)], while a double-blind clinical trial with glucosamine showed definite benefits in osteoarthritis with respect to both pain and radiographic joint appearance [Reginster et al., Lancet 337:252 (2001)]. However, less than 5% of the chondroitin sulfate in commercially available preparations is absorbed orally, because the size of the molecule and the degree of sulfation impede its absorption from the gastrointestinal tract. Furthermore, such commercial preparations use chondroitin sulfate obtained from cow trachea, with the possible danger of contracting spongiform encephalopathy or "mad cow disease". In fact, the European Union has banned even cosmetics that contain bovine-derived products. Web site: http://www.delphion.com/details?pn=US06624148__ •
Synergistic agents for enhancing tissue repair Inventor(s): Jaffe; Russell (10430 Hunter View, Vienna, VA 22181) Assignee(s): none reported Patent Number: 6,620,798 Date filed: June 6, 2000 Abstract: Methods for the repair, reconstruction and protection of tissue using compositions containing flavonoids and/or flavonols, including simultaneous administration of agents in order to obtain synergistic effects from the combinations taught and claimed herein. The administration of the flavonols and /or flavonoids in conjuction with compositions containing vitamin C and/or salts and esters of vitamin C provides advantageous sparing of autocoids (internal steroids). The simultaneous administration of flavonols and /or flavonoids to compositions containing glucosamine and or glucosamine sulfate and chondroitin stimulates rapid improvement in joint function. The addition to the flavonoids and/or flavonols to previously administered compositions is a most convenient method of achieving enhanced benefits. The use of combinations of flavonoids and flavonols for use in relieving pain is also a part of the invention. Excerpt(s): This invention is related to the repair, reconstruction and protection of tissue using compositions containing flavonoids and/or flavonols. It has been known that phenolic compounds, including flavonoids and flavonols, have anti-inflammatory properties. It has been known that several flavonones, flavonols, isoflavonones and
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catechins, can inhibit the proliferation of inflammatory (granulation) tissue. These agents can decrease capillary permeability and strengthen the blood vessel wall, thus preventing vascular fragility. The agents have been shown to have affinity for and enhance synthesis of connective tissue. Some flavonoids have been found to stimulate collagen and elastin cross-linking. It is believed that proline hydroxylation and modulation of polysaccharide production and function may be among the mechanisms by which benefit occurs. However, bioaction of these compounds, when given alone, is inadequate to provide desired clinical results. It is necessary to find more effective means of delivering clinical benefits that can arise from exposure to flavonoids. Web site: http://www.delphion.com/details?pn=US06620798__ •
Tissue maintenance system that applies rhythmic pulses of pressure Inventor(s): Nevo; Zvi (Herzliya, IL), Robinson; Dror (Shimson, IL) Assignee(s): Ramot at Tel Aviv University Ltd. (Ramot Aviv, IL) Patent Number: 6,632,651 Date filed: July 6, 1999 Abstract: A growth support scaffold for cells and tissue is formed of naturally derived connective or skeletal tissue which has been treated for elimination of cellular and cytosolic elements, and modified by cross-linking with hyaluronic acid, proteoglycans, glycosaminoglycans, chondroitin sulfates, heparan sulfates, heparins or dextran sulfates. The scaffold may contain cell adhesive molecules and growth factors, and can be formulated as a malleable prosthesis. A tissue maintenance system is provided containing a chamber having a constant atmosphere which may contain the scaffold impregnated with cells, a medium-containing reservoir, a pump which can be computer controlled for circulating the medium between the chamber and reservoir and may change direction of medium flow every 1 to 3 minutes, and a pressure generator, which can be the pump, for producing rhythmic pulses of pressure such as between 0.5 to 30 atm and frequency of 5-300 per minute. Excerpt(s): The invention concerns scaffold matrixes for supporting three-dimensional tissues and systems for maintaining three-dimensional viable tissues. The following publications are believed to be relevant as background of the invention. U.S. Pat. No. 5,843,182. Web site: http://www.delphion.com/details?pn=US06632651__
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Topically applied creatine containing composition Inventor(s): Stoll; David M. (9735 Wilshire Blvd. Suite 418, Beverly Hills, CA 90212) Assignee(s): none reported Patent Number: 6,413,552 Date filed: August 28, 2001 Abstract: The present invention is a stable topical creatine application suitable for absorption directly through the skin into the underlying muscle without traveling through the blood system for the purpose of increasing muscle energy. It is created by combining creatine with phosphoric acid in a cosmetically elegant vehicle suitable for
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topical use. Chondroitin sulfate and glucosamine can also be added. Topical creatine avoids the side effects of oral creatine supplements. Excerpt(s): The present invention relates to the field of muscle stimulation and more particularly to enhancing the production of the energy used to cause contractions and expansions in the muscles of mammals. Creatine is an important source of providing energy to muscles through its role in adenosine triphosphate (ATP) formation. ATP is the fuel source for muscle contraction. It is formed when adenosine diphosphate (ADP), adds another phosphate group to form ATP. Creatine provides the source for replacing the phosphate group to convert ADP to ATP. As such, it is an integral part of the muscle contraction and expansion process. The more creatine available to muscles, the more ADP can be converted to ATP for use by those muscles. Therefore, for persons involved in strenuous physical activities, such as athletes, a constant source of creatine is vital in order to maintain muscle energy levels. Creatine is a popular nutritional supplement useful as an energy source for muscles. Chemically, creatine is N-methyl-Nguanylglycine. Creatine is biosynthesized through the transamidination and transmethylation of the amino acids glycine, arginine and methionine. Web site: http://www.delphion.com/details?pn=US06413552__ •
Treatment of cystitis-like symptoms administration of a challenge solution
with
chondroitin
sulfate
following
Inventor(s): Hahn; Sungtack Samuel (Scarborough, CA) Assignee(s): Stellar International Inc. (London, CA) Patent Number: 6,083,933 Date filed: April 19, 1999 Abstract: Cystitis of the bladder and urinary tract, particularly interstitial cystitis, are treated using effective unit doses of chondroitin sulfate. Further, cystitis patients are screened for their response to a given cystitis treatment using a method in which patients are first challenged with an irritant and then treated with a selected cystitis therapeutic. Candidates for further treatment are identified as those patients who on receiving the selected therapeutic, report relief from at least one symptom elicited with the irritant. Also provided are kits comprising solutions for carrying out this screening method. Excerpt(s): The invention relates to therapeutic and diagnostic methods useful in the treatment and assessment of cystitis, including interstitial cystitis, and related bladder conditions. Interstitial cystitis is a bladder condition associated with discomfort and pain elicited by urinary irritants, causing urgency for, and increased frequency of, urination. Because its cause is poorly understood, the development of useful treatments has followed approaches that are largely empirical and even haphazard, and these approaches have failed to yield more than a few useful therapeutic agents and treatments. As described by Sant and La Rock in Interstitial Cystitis, Vol. 21 (1), February 1994 at p.73, current therapies include pharmacotherapy, with intravesical use of dimethyl sulfoxide being the only therapy approved by the FDA. Still, a variety of other agents are in use to treat symptoms of interstitial cystitis, either alone or in combination with DMSO. Such agents include sodium oxychlorosene (Clorpactin), heparin, hyaluronic acid, steroid, sodium bicarbonate, silver nitrate, sodium pentosanpolysulfate, cromolyn sodium, lidocaine and doxorubicin. Many of these agents can be delivered orally, but to be effective are most typically delivered by
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instillation either as monotherapy, combination therapy or sequential therapy. These agents and therapies target the bladder mucosal lining, and provide symptomatic relief of pain, frequency and urgency. Of these therapies, however, few offer relief over sustained periods. There is a need to provide, on a cost-effective basis, agents and therapies that are useful to treat cystitis, including interstitial cystitis and related conditions of the bladder and urinary tract that result from an eroded mucosal lining. There is also a need to provide methods by which patients can be screened to reveal therapeutic agents effective to treat that patient's particular condition. It is accordingly an object of the present invention to provide such a diagnostic screening method. Web site: http://www.delphion.com/details?pn=US06083933__
Patent Applications on Chondroitin As of December 2000, U.S. patent applications are open to public viewing.10 Applications are patent requests which have yet to be granted. (The process to achieve a patent can take several years.) The following patent applications have been filed since December 2000 relating to chondroitin: •
Aminosugar, glycosaminoglycan, and S-adenosylmethionine composition for the treatment and repair of connective tissue Inventor(s): Hammad, Tarek; (Baltimore, MD), Henderson, Robert W.; (Baldwin, MD) Correspondence: Covington & Burling; Patent Docketing; 1201 Pennsylvania Avenue, NW; Washington; DC; 20004-2401; US Patent Application Number: 20020032169 Date filed: April 16, 2001 Abstract: A composition for the protection, treatment and repair and for reducing the inflammation of connective tissue in mammals and a method for the treatment of connective tissue in mammals by the administration of the composition. The composition includes S-Adenosylmethionine (SAM), and a component selected from an aminosugar or salts thereof (e.g., glucosamine) or glycosaminoglycans (e.g., chondroitin salts) or mixtures or fragments thereof. The composition optionally includes manganese which promotes the production of connective tissue matrix. The composition also optionally includes methyl donors or methyl donor cofactors, such as vitamin B12, vitamin B6, folic acid, dimethylglycine or trimethylglycine. Excerpt(s): The present application is a continuation-in-part of U.S. patent application Ser. No. 08/779,996, filed Dec. 23, 1996, the disclosure of which is incorporated by reference herein in its entirety. The present invention relates to compositions for the repair and reduction of inflammation of connective tissue in humans and animals and, in particular, to compositions capable of promoting anti-inflammation, chondroprotection, chondromodulation, chondrostabilization, chondrometabolization and the repair and replacement of human and animal connective tissue. The connective tissues of humans and animals are constantly subjected to stresses and strains from mechanical forces and from diseases that can result in afflictions, such as arthritis, joint inflammation and stiffness. Indeed, connective tissue afflictions are quite common,
10
This has been a common practice outside the United States prior to December 2000.
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presently affecting millions of Americans. Further, such afflictions can be not only painful but, in their extreme, debilitating. Web site: http://appft1.uspto.gov/netahtml/PTO/search-bool.html •
Anti-inflammatory and connective tissue repair formulations Inventor(s): Kuhrts, Eric Hauser; (Bodega, CA) Correspondence: Wilson Sonsini Goodrich & Rosati; 650 Page Mill Road; Palo Alto; CA; 943041050 Patent Application Number: 20020086070 Date filed: October 17, 2001 Abstract: Disclosed is a pharmaceutical composition including a therapeutic quantity of an a joint restorative compound selected from aminosugars, chondroitin, collagen 2, or methyl sulfonyl methane; and a therapeutic quantity of a COX-2 inhibitor having an IC50-WHMA COX-2/COX-1 ratio ranging from about 0.23 to about 3.33. Also disclosed are methods for the treatment, regeneration, and repair of connective tissue in mammals and methods for treating osteoarthritis, rheumatoid arthritis or acute pain utilizing the disclosed Excerpt(s): This is a continuation-in-part of serial number 09/524,416, filed Mar. 11, 2000, which is hereby incorporated by reference as if reproduced fully herein. This invention relates to therapeutic compositions that exhibit anti-inflammatory and joint repair properties. The compositions are useful for treating osteoarthritis and rheumatoid arthritis, as well as connective tissue damaged by trauma or injury. Osteoarthritis is a degenerative joint disease and is the most common form of arthritis, affecting over 20 million people in America alone, most of which are 45 years old or older. Osteoarthritis causes the cartilage that covers the bone ends to deteriorate, causing pain, inflammation, and disability. Rheumatoid arthritis affects fewer people than osteoarthritis, nonetheless rheumatoid arthritis still affects just over 2 million people in the United States alone. There are also a large number of people who suffer from problems with connective tissue damaged by trauma or injury. Web site: http://appft1.uspto.gov/netahtml/PTO/search-bool.html
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Attenuation of fibroblast proliferation Inventor(s): Cauchon, Elizabeth; (Ile Perrot, CA), Denholm, Elizabeth M.; (Pointe Claire, CA), Silver, Paul J.; (Spring City, PA) Correspondence: Patrea L. Pabst; Arnall Golden & Gregory, Llp; 2800 One Atlantic Center; 1201 West Peachtree Street; Atlanta; GA; 30309-3450; US Patent Application Number: 20020102249 Date filed: December 1, 2000 Abstract: Highly purified and specific glycosaminoglycan degrading enzymes, chondroitinase B and chondroitinase AC, are used to treat fibroproliferative diseases. The enzymatic removal of chondroitin sulfate B (dermatan sulfate), and to a lesser extent, chondroitin sulfate A or C, from cell surfaces effectively decreases growth factor receptors on the cells and thereby decreases the cell proliferative response to such growth factors. In addition, removal of chondroitin sulfates reduces secretion of
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collagen, one of the major extracellular matrix components. Through the combined inhibition of fibroblast proliferation and collagen synthesis, treatment with chondroitinase B or chondroitinase AC decreases the size of fibrous tissue found in psoriasis, scleroderma, keloids, pulmonary fibrosis and surgical adhesions. Excerpt(s): The present invention is a method and composition using chondroitinase B and chondroitinase AC, glycosaminoglycan degrading enzymes, to inhibit the formation of fibrotic tissue. This application claims priority to U.S. Ser. No. 60/168,518, filed Dec. 2, 1999. Proteoglycans on the cell surface and in the extracellular matrix contain variable glycosaminoglycan chains, which include heparan sulfate and chondroitin sulfates A, B, or C. While some proteoglycans contain only one type of glycosaminoglycan, others contain a mixture of heparan and chondroitin sulfates (Jackson et. al., Physiol. Rev. 71:481-530,1991). Extracellular proteoglycans form a structural framework for cells and tissues, and together with cell-associated proteoglycans, have major functions in regulating cell adhesion, migration, and proliferation. The functions of proteoglycans and their component parts have been extensively studied, with much of the emphasis on the roles of heparin and heparan sulfate on cell metabolism (Kjellen, L., and Lindahl, U. (1991) Ann. Rev. Biochem. 60:443-475; Vlodavsky, et al. (1995) Thrombosis Haemostasis 74:534-540; Yayon, et al. (1991) Cell 64:841-848)). Much less is known about the biological activities of proteoglycans containing chondroitin sulfate glycosaminoglycans, and in particular, their effects on cell proliferation. Web site: http://appft1.uspto.gov/netahtml/PTO/search-bool.html •
Cartilage enhancing food supplements with sucralose and methods of preparing the same Inventor(s): Stone, Kevin R.; (Mill Valley, CA) Correspondence: Mcdermott, Will & Emery; 28 State Street; Boston; MA; 02109; US Patent Application Number: 20030124200 Date filed: July 1, 2002 Abstract: A food supplement, either in the form of a snack bar or a beverage, which contains one or more cartilage enhancing supplements and sucralose is provided. The cartilage supplements include chondroitin, glucosamine, and hyaluronic acid. The food supplement may additionally be fortified with cetyl myristoleate. The beverage is a mixture of a juice drink base which may include a water-based fruit flavored juice prepared using a pasteurization process at a relatively high temperature and a cartilage supplement solution which includes a cartilage supplement prepared at a relatively low temperature. The beverage may be carbonated, non-carbonated or concentrated. The preferred cartilage supplement is glucosamine, preferably associated with a counter ion, more preferably as glucosamine hydrochloride. Excerpt(s): This application is a continuation-in-part of U.S. patent application Ser. No. 09/598,634, filed Jun. 21, 2000, which is a continuation-in-part of U.S. patent application Ser. No. 09/338,021, filed Jun. 22, 1999, the disclosures of which are incorporated herein by references. The present invention relates to food supplements, such for example, snack bars and beverages that are fortified with one or more cartilage supplements. Nutritional bars and energy drinks are convenient nutritional supplements, particularly for those persons too busy to eat regular meals and for hikers, cyclists, runners or other athletes who need prepackaged, ready-to-eat, high-energy snacks while they are exercising. Such bars and drinks are also convenient nutritional supplements for the
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elderly who need prepackaged, ready-to-eat snacks. Additionally, such food supplements can supply consumers with the necessary vitamins and minerals specified in the recommended daily allowances provided by the U.S. government. Web site: http://appft1.uspto.gov/netahtml/PTO/search-bool.html •
Chondroitin polymerase and DNA encoding the same Inventor(s): Kimata, Koji; (Aichi, JP), Ninomiya, Toshio; (Tokyo, JP), Sugiura, Nobuo; (Gifu, JP) Correspondence: Oblon, Spivak, Mcclelland, Maier & Neustadt, P.C.; 1940 Duke Street; Alexandria; VA; 22314; US Patent Application Number: 20030109693 Date filed: August 12, 2002 Abstract: A chondroitin polymerase having such properties that it transfers GlcUA and GalNAc alternately to a non-reduced terminal of a sugar chain from a GlcUA donor and a GalNAc donor, respectively, and the like; and a process for producing the chondroitin polymerase. Excerpt(s): The present invention relates to a novel chondroitin polymerase (chondroitin synthase), a DNA encoding the same, a method for producing the chondroitin polymerase, a method for producing a sugar chain having the disaccharide repeating unit of chondroitin, a hybridization probe for the chondroitin polymerase and the like. First, abbreviations commonly used in the present specification are described. In the formulae and the like, "GlcUA", "GalNAc", "GlcNAc", "UDP" and "-" represent D-glucuronic acid, N-acetyl-D-galactosamine, N-acetyl-D-glucosamine, uridine 5'-diphosphate and a glycosidic linkage, respectively. Web site: http://appft1.uspto.gov/netahtml/PTO/search-bool.html
•
Chondroitin sulfate containing viscoelastics for use in treating joints Inventor(s): Jafari, Masoud R.; (Arlington, TX) Correspondence: Alcon Research, LTD.; R&d Counsel, Q-148; 6201 South Freeway; Fort Worth; TX; 76134-2099; US Patent Application Number: 20030086899 Date filed: November 13, 2002 Abstract: Disclosed are viscoelastic compositions and methods of their use in treating joints, especially in conjunction with trauma and osteoarthritis. Excerpt(s): This application is a continuation-in-part of pending U.S. patent application Ser. No. 09/857,543 filed Jun. 6, 2001, which is a national application under 35 U.S.C.sctn. 371 of PCT Application Serial No. PCT/US01/08064 filed Mar. 14, 2001, which draws priority from U.S. Provisional Application Serial No. 60/189,179 filed Mar. 14, 2000, now abandoned. The present invention relates to the use of viscoelastics, typically in surgery, to prevent or reduce unwanted tissue adhesion and/or fibrosis subsequent to the trauma or surgical insult. The methods of the present invention are particularly useful in the field of otic therapy, and especially in therapies associated with the treatment of middle ear conditions which arise as a consequence of disease, injury,
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surgery and the like. The compositions and methods of the present invention are particularly useful in mastoidectomy and tympanoplasty surgeries. In addition, the compositions of the present invention may be used as a packing agent, with or without a therapeutic agent, for the management of otitis externa in the external ear canal. Of the three ear compartments, the middle ear is perhaps the most prone to trauma which can result in loss of hearing. One reason for this is that the tympanic membrane and the ossicular chain are extremely delicate. Any trauma which impedes or alters the motility of the respective components will necessarily impact the transducer function they serve. The three tiny bones of the ossicular chain and reconstructions thereof are particularly susceptible to impaired function if the ossicular chain is permitted to collapse before it is sufficiently healed. Such collapse can result in undesirable adhesions and fibrosis that can severely limit the motility of the ossicular chain members and hence their ability to serve the transducer function. In order to stabilize the tympanic membrane and the ossicular chain, at the end of middle ear surgery, the middle ear compartment is typically "packed" with some type of gel product. Web site: http://appft1.uspto.gov/netahtml/PTO/search-bool.html •
Chondroprotective/restorative compositions and methods of use thereof Inventor(s): Pierce, Scott W.; (Lexington, KY) Correspondence: Isaac A. Angres; Suite 301; 2001 Jefferson Davis Highway; Arlington; VA; 22202; US Patent Application Number: 20020068718 Date filed: October 2, 2001 Abstract: The instant invention provides a method of treating or preventing osteoarthritis, joint effusion, joint inflammation and pain, synovitis, lameness, post operative arthroscopic surgery, deterioration of proper joint function including joint mobility, the reduction or inhibition of metabolic activity of chondrocytes, the activity of enzymes that degrade cartilage, the reduction or inhibition of the production of Hyaluronic acid, said method comprising orally administering to a mammalian species a therapeutically effective amount of Hyaluronic Acid or pharmaceutically acceptable salts thereof. Additionally, compositions containing hyaluronic acid; chondroitin sulfate, and glucosamine sulfate in a paste formulation are also disclosed which can be administered on their own or can be used as a feed additive. Excerpt(s): The present invention relates to medically useful preparations based on hyaluronic acid and pharmaceutically acceptable salts thereof, a naturally-occurring substance found in animal tissue, and especially in rooster comb, vitreous humour, umbilical cords, and synovial fluid of mammals. This invention also relates to new orally administrable formulations containing hyaluronic acid. The instant invention is also directed to chondroprotective/restorative compositions containing hyaluronic acid. This invention also relates to new pharmaceutical formulations containing hyaluronic acid. The invention is further directed to a new veterinary formulations containing hyaluronic acid. This invention further relates to orally administrable veterinary formulation containing hyaluronic acid. The present invention is also directed to veterinary formulations containing hyaluronic acid and additional bio-effective active ingredients such as bioactive agents useful in the treatment of domesticated animals especially horses. This invention also provides methods for treating horses in need of chondroprotection. The invention is further directed to pharmaceutical compositions containing hyaluronic acid, glucosamine and chondroitin. The present invention also
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relates to a method of treating aseptic synovitis in horses with hyaluronic acid alone or in combination with other active ingredients. More specifically, the present invention is also intended for therapeutic treatments of arthritis and related conditions using pharmaceutical compositions containing hyaluronic acid as well as other active ingredients effective ion the treatment of joint diseases. The compositions of the invention are particularly useful in the veterinary field but are also very useful in treatment of humans. This invention further relates to the oral administration of forms of hyaluronic acid and pharmaceutically acceptable salts thereof such as sodium hyaluronate, and orally administrable dosage forms containing forms of hyaluronic acid, for the prevention and/or treatment of diseases such as osteoarthritis, joint effusion, joint inflammation and pain, synovitis, and many other diseases associated with cartilage degeneration. Web site: http://appft1.uspto.gov/netahtml/PTO/search-bool.html •
Cicatrizant hydrocolloidal patch containing hyaluronic acid and chondroitin sulphate Inventor(s): Garavani, Alberto; (Massagno, CH), Rapaport, Irina; (Rovio, CH) Correspondence: Abelman Frayne & Schwab; Attorneys AT Law; 150 East 42nd Street; New York; NY; 10017; US Patent Application Number: 20030124175 Date filed: March 21, 2002 Abstract: Cicatrizant hydrocolloidal patch comprising:a) a support layer,b) an adhesive layer containing an adhesive polymer, at least one hydrocolloid, hyaluronic acid or a pharmaceutical salt thereof, chondroitin sulphate or a pharmaceutical salt thereof,c) a protective layer removable at the moment of use. Excerpt(s): The present invention concerns a cicatrizant hydrocolloidal patch and the relative preparation process. Cicatrizant pharmaceutical formulations for topical use, based on hyaluronic acid or a pharmaceutical salt thereof, have been known for some time. For instance EP 0480198 describes pharmaceutical compositions containing the sodium salt of hyaluronic acid and antiseptic substances for topical use. However, these compositions are in hydrogel form and have the disadvantage of adding liquid to the wound when applied to it, hence making it even more difficult to eliminate the exudate from the wound. Web site: http://appft1.uspto.gov/netahtml/PTO/search-bool.html
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Composition for the relief of joint pain and myofascial pain and method of preparing same Inventor(s): Knigge, Jan Donald; (St. Petersburg, FL) Correspondence: N. Whitney Wilson; Bryan Cave Llp; 245 Park Avenue; New York; NY; 10167-0034; US Patent Application Number: 20030045503 Date filed: September 30, 2002 Abstract: A stable, formulation comprising glucosamine and chondroitin compounds in a base which can be used for topical application to relieve joint pain and myofascial pain. A method of preparing the composition by adding the glucosamine and
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chondroitin after the rest of the components of the formulation have been mixed and heated is also disclosed. Excerpt(s): This invention relates to a topically applied composition for the treatment of joint pain and myofascial pain, a process for preparing the composition, and a method of treating joint pain and, myofascial pain using the composition. Joint pain and myofascial pain can be caused by arthritis, cartilage injury or disease, and other sources. Patients can find such pain to be debilitating, and have used a variety of treatments for relief of pain, including formulations administered orally, parenterally, and topically. A popular form of treatment for joint pain and myofascial pain is the topical application of pain relieving ointments which contain menthol. Formulations for topical application can either be water-based or substantially anhydrous. For many applications, anhydrous (i.e. oil-based) formulations are preferable because anhydrous formulations will not evaporate like those containing water or alcohol. Anhydrous formulations, therefore, are easier to use in massaging applications. Web site: http://appft1.uspto.gov/netahtml/PTO/search-bool.html •
Compositions and methods directed towards sore muscles and joints Inventor(s): Reynolds, Peter L.; (Marietta, GA) Correspondence: Thomas, Kayden, Horstemeyer & Risley, Llp; 100 Galleria Parkway, NW; Ste 1750; Atlanta; GA; 30339-5948; US Patent Application Number: 20030185904 Date filed: March 26, 2002 Abstract: Chemical formulations and methods for reducing muscle and joint soreness are disclosed. A representative chemical formulation includes compounds such as a selenium-compound, chondroitin sulfate, glucosamine, and/or methylsulfonylmethane. A representative method for reducing muscle and joint soreness includes administering the chemical formulation to a host. Excerpt(s): The present invention is generally related to chemical formulations and methods for administration of the chemical formulation to mammals and, more particularly, is related to chemical formulations directed towards reducing muscle and joint soreness and methods of administration thereof. Often muscle soreness and joint pain occur concurrently as a result of physical exertion or old age. In addition, joint pain may occur as a result of arthritis or other degenerative joint diseases, which may also indirectly cause muscle soreness. Muscle and joint soreness occur in most mammals and, in particular, occur in humans, horses, dogs, and cats. The soreness creates many problems, such as making normal mammalian actions difficult and painful. These actions include walking, squatting, running, grasping, etc. To alleviate this discomfort, multiple pain relievers need to be taken, e.g., one pain reliever to address the muscle soreness and another pain reliever to address joint soreness. Multiple pain relievers, e.g. pills or tablets, can be difficult to administer in same mammals, such as horses, dogs, and cats. Further, there are significant costs associated with purchasing multiple pain relievers. Selenium compounds, both organic and inorganic, and methylsulfonylmethane have been used for years as mineral supplements to maintain good health and relieve muscle soreness, but not joint pain or soreness. Glucosamine has been shown to be effective for reducing arthritis and soreness of the joints, but not muscle soreness. Web site: http://appft1.uspto.gov/netahtml/PTO/search-bool.html
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•
Cross-linked polysaccharide drug carrier Inventor(s): Liu, Lin Shu; (San Luis Obispo, CA), Spiro, Robert C.; (Half Moon Bay, CA), Thompson, Andrea Y.; (Mountain View, CA) Correspondence: Fish & Richardson P.C.; 500 Arguello Street, Suite 500; Redwood City; CA; 94063; US Patent Application Number: 20030012765 Date filed: September 17, 2001 Abstract: A carrier and a method for preparing it are provided for use in the delivery of therapeutic agents. A polysaccharide is reacted with an oxidizing agent to open sugar rings on the polysaccharide to form aldehyde groups. The aldehyde groups are reacted to form covalent oxime linkages with a second polysaccharide and each of the first and second polysaccharide is selected from the group consisting of hyaluronic acid, dextran, dextran sulfate, chondroitin sulfate, dermatan sulfate, keratan sulfate, heparan, heparan sulfate and alginate. Excerpt(s): This application is a continuation of U.S. application Ser. No. 09/110,381, filed Jul. 1, 1998, which is a continuation-in-part of U.S. application Ser. No. 08/887,994, filed Jul. 3, 1997. The present invention is directed to biodegradable carriers for the delivery of therapeutic agents, methods of making the carriers and methods of using the carriers. There is a clinical demand for carriers of therapeutic agents that are biodegradable, biocompatible and which allow for targeted delivery and controlled release of the therapeutic agent. Web site: http://appft1.uspto.gov/netahtml/PTO/search-bool.html
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Effervescent glucosamine, chondroitin and MSM formula Inventor(s): Phillips, Cleve Alan; (Hayward, CA) Correspondence: Williams Mullen; 1 Old Oyster Point Road; Suite 210; Newport News; VA; 23602; US Patent Application Number: 20030180389 Date filed: March 20, 2003 Abstract: A composition which acts to protect, maintain and repair connective tissue in mammals. The composition includes glucosamine, chondroitin sulfate and sulfur in an effervescent base as its major elements. The effervescent base includes one or more acids and one or more bases and may also include a starch, a flavoring agent and a coloring agent. The composition can be formed into a tablet or can be granular. The tablet or granular mixture is dissolved in a neutral pH liquid such as water for consumption purposes. Excerpt(s): The present application claims priority from U.S. Provisional Application Ser. No. 60/150,552, filed Aug. 25, 1999. The present invention pertains to the field of nutritional formulas. Specifically, the present invention pertains to an improved formula for delivering glucosamine, chondroitin and MSM to the body. It is well known that products containing glucosamine, chondroitin and MSM can aid in the protection, maintenance and repair of connective tissue in mammals. Such tissues are regularly exposed to stresses and strains from forces which cause problems such as arthritis, joint
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inflammation and stiffness. These problems can affect all joints in both humans and animals and can be both painful and debilitating to the sufferer. While the optimal treatment is relief from the force causing the joint problems, this is not always possible. Web site: http://appft1.uspto.gov/netahtml/PTO/search-bool.html •
Food product supplemented with proteoglycan precursors Inventor(s): Bahoshy, Robert; (Long Beach, CA) Correspondence: Peng Chen; Morrison & Foerster Llp; Suite 500; 3811 Valley Centre Drive; San Diego; CA; 92130-2332; US Patent Application Number: 20030134825 Date filed: January 3, 2003 Abstract: A food product for supplementing the proteoglycan precursor intake of humans suffering from joint related ailments and a method of making and administering such a food product is disclosed. More specifically, a settable food product, supplemented with glucosamine and chondroitin, which comes in a suitable form, e.g., a pudding or pie filling, is disclosed, along with a method of making and administering the product to persons in need thereof. Excerpt(s): This application claims the benefit of Provisional Patent Application No. 60/344,053 filed on Jan. 3, 2002, and Provisional Patent Application No. 60/353,051 filed on Jan. 29, 2002 under 35 U.S.C.sctn.119(e). The contents of the above-referenced applications are incorporated herein in their entireties. Throughout this application, various references are referred to. Disclosures of these publications in their entireties are hereby incorporated by reference into this application to more fully describe the state of the art to which this invention pertains. The present invention generally relates to food compositions for the treatment of joint related ailments, and methods for making and administering these compositions. In particular, the present invention relates to the preparation of compositions including proteoglycan precursors and method for administering these precursors in a beneficial and appetizing manner to persons in need thereof. Web site: http://appft1.uspto.gov/netahtml/PTO/search-bool.html
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Hair dye composition Inventor(s): Mitamura, Joji; (Tokyo, JP), Noguchi, Mutsumi; (Tokyo, JP), Onuki, Takeshi; (Tokyo, JP) Correspondence: Birch Stewart Kolasch & Birch; PO Box 747; Falls Church; VA; 220400747; US Patent Application Number: 20030074743 Date filed: May 30, 2002 Abstract: A one-pack aerosol type hair dye composition which comprises an oxidation color and an oxidase, characterized in that at least one water-soluble high-molecular compound selected from hydroxypropyl cellulose, carboxymethyl cellulose, xanthan gum, gum guaiac, locust bean gum, gum arabic, tragacanth gum, karaya gum, gellan gum, pectin, carrageenan, furcellaran, alginic acid and salts thereof, hyaluronic acid and salts thereof, chondroitin sulfuric acid and salts thereof, ethylene oxide polymer,
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polyacrylic acid and salts thereof, acrylic copolymers and salts thereof, polyvinyl pyrrolidone, vinyl pyrrolidone copolymers, polyvinyl acetate, vinyl acetate copolymers, carboxy vinyl polymer is formulated. Excerpt(s): This invention relates to a hair dye composition of a one-pack (onecomponent) aerosol type, and more particularly, to an oxidation-type hair dye composition of the one-pack aerosol type wherein a hair dye composition sprayed from an aerosol container exhibits good foam retention without dripping of liquid in use, has good stability with time and shows an excellent dyeing effect after long-time storage, and can be improved in foaming property. The oxidation-type hair dye is one which is used to dye white hair usually by mixing for reaction between an oxidation color (first agent) and an oxidizing agent (second agent) on use and acting the mixture on hair. Although these hair dyes may take a liquid, powdery or paste form in use, users should employ them in every time after mixing the first agent with the second agent for all the types thereof, so that the way to use them is troublesome and thus, it has been required to overcome the trouble from the standpoint of the usability. In recent years, taking the usability into consideration, a one-pack aerosol type hair dye composition has been proposed. With a hair dye, if a liquid is dripped upon application to hair or after the application, a problem rises in that clothes or a floor is stained therewith. To avoid this, with a one-pack aerosol type product, it is desirable that liquid dripping be unlikely to occur upon spraying from a container. Web site: http://appft1.uspto.gov/netahtml/PTO/search-bool.html •
Heparin/heparosan synthase from P. multocida and methods of making and using same Inventor(s): DeAngelis, Paul L.; (Edmond, OK) Correspondence: Dunlap, Codding & Rogers P.C.; PO Box 16370; Oklahoma City; OK; 73114; US Patent Application Number: 20030099967 Date filed: May 8, 2002 Excerpt(s): The presently claimed and disclosed invention relates, in general, to dual action heparin synthases and, more particularly, to dual action heparin synthases obtained from Pasteurella multocida. The presently claimed and disclosed invention also relates to heparosan, heparin and heparin-like molecules produced according to recombinant techniques and methods of using such molecules. The presently claimed and disclosed invention also relates to methods, and molecules produced according to such methods, for using the presently claimed and disclosed heparosan and/or heparin synthases for polymer grafting and the production of non-naturally occurring chimeric polymers incorporating stretches of one or more acidic GAG molecules, such as heparin, chondroitin, hyaluronan, and/or heparosan. Glycosaminoglycans [GAGs] are long linear polysaccharides consisting of disaccharide repeats that contain an amino sugar and are found in most animals. Chondroitin [.beta.(1,4)GlcUA-.beta.(1,3)GalNAc].sub.n, heparin/heparosan [.beta.1,4)GlcUA-[.alpha.(1,4)GlcNAc].sub.n, and hyaluronan [.beta.(1,4)GlcUA-.beta.(1,3)GlcNAc].sub.n are the three most prevalent GAGs found in humans and are also the only known acidic GAGs. Chondroitin and heparin typically have n=20 to 100, while hyaluronan typically has n=10.sup.3. Chondroitin and heparin are synthesized as glycoproteins and are sulfated at various positions in vertebrates. Hyaluronan is not sulfated in vertebrates. A substantial fraction of the GlcUA residues of heparin and chondroitin are epimerized to form iduronic acid. A simplified
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nomenclature has been developed for these GAGs. For example, heparin/heparosan's structure is noted as.beta.4-GlcUA-.alpha.4-GlcNAc. The capsular polysaccharide produced by the Type D strain of Pasteurella multocida is N-acetyl heparosan (heparosan is unmodified heparin--i.e. sulfation or epimerization have not occurred). In vertebrates, one or more modifications including O-sulfation of certain hydroxyls, deacetylation and subsequent N-sulfation, or epimerization of glucuronic acid to iduronic acid modifies the precursor N-acetyl heparosan to heparin/heparan. Hereinafter, for convenience and/or ease of discussion, heparin and/or heparosan are defined as polymers having the.beta.4GlcUA-.alpha.4GlcNAc backbone. Web site: http://appft1.uspto.gov/netahtml/PTO/search-bool.html •
Hyaluronic acid and chondroitin sulfate based hydrolyzed collagen type II and method of making same Inventor(s): Ishaq, Suhail; (Diamond Bar, CA) Correspondence: Stetina Brunda Garred & Brucker; 75 Enterprise, Suite 250; Aliso Viejo; CA; 92656; US Patent Application Number: 20030091652 Date filed: November 13, 2001 Abstract: Hydrolyzed collagen type II powder compositions for inducing cartilage formation in an individual, method of preparing the compositions and use of the compositions in treating connective tissue disorder, replenishing skin viscoelasticity. The compositions are administered through an orally ingestible delivery medium for absorption into the gastrointestinal tract. The compositions are administered through a topical delivery medium for absorption into a dermis of the individual. Excerpt(s): The present invention relates to hydrolyzed collagen type II powder compositions for inducing cartilage formation in an individual, a method of preparing the compositions and the use of the compositions in treating connective tissue disorder and replenishing skin viscoelasticity. Studies have shown that collagen is a complex structural protein which provides strength and flexibility to skin, hair and nails. Collagen is an essential and major component of muscles, tendons, cartilage, ligaments, joints and blood vessels in the human body. There are three main types of collagen: I, II and III. Types I and III are primarily found in skin, tendon and bone. In contrast, type II is found predominantly in articular cartilage. Collagen is an unusual protein, in that the proportion of glycine residues is nearly one-third, which is unusually high in comparison to other typical proteins. Proline is also present to a much greater extent in collagen than in most other proteins. Moreover, collagen contains two amino acids, 4hydroxyproline and 5-hydroxylysine, that are found in very few other proteins. The amino acid sequence of collagen is remarkably regular, nearly every third amino acid being glycine. In addition, the sequence glycine-proline-hydroxyprol- ine recurs frequently. In contrast, globular proteins rarely exhibit regularities in their amino acid sequences (Stryer, L., Biochemistry, Third Edition, W. H. Freeman and Co., New York, 1988, pp. 262). In 1986, collagen was sold for the first time in the United States for use as a food supplement. Collagen (a mixture of Types I and III) was extracted from calf skin tissue, hydrolyzed and prepared in powdered form for use as a dietary supplement. The composition was sold under the name "Hydrolyzed Collagen Beauty Supplement.TM." (Smarter Nails & Hair, Inc., Newport Beach, Calif.). In 1987, "Hydrolyzed Collagen Beauty Supplement Tablet.TM." (Smarter Nails & Hair, Inc., Newport Beach, Calif.) was
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sold which comprised collagen powder and 10 mg vitamin C compressed into 1,000 mg tablets. Web site: http://appft1.uspto.gov/netahtml/PTO/search-bool.html •
HYALURONIDASE PREPARATION FOR OPHTHALMIC ADMINISTRATION AND ENZYMATIC METHODS FOR ACCELERATING CLEARANCE OF HEMORRHAGIC BLOOD FROM THE VIREOUS BODY OF THE EYE Inventor(s): ARAGON, CARPIO; (TIJUANA, MX), GUTIERREZ FLORES, JOSE LUIS; (TIJUANA, MX), KARAGEOZIAN, HAMPAR L.; (SAN JUAN CAPISTRANO, CA), KARAGEOZIAN, VICKEN H.; (SAN JUAN CAPISTRANO, CA), KENNEY, MARIA CRISTINA; (MALIBU, CA), NESBURN, ANTHONY B.; (MALIBU, CA) Correspondence: Nancy Ways Vensco; Knobbe, Martens, Olson, And Bear, Llp; 620 Newport Center Drive; 16th FL.; Newport Beach; CA; 92660; US Patent Application Number: 20020071837 Date filed: December 2, 1999 Abstract: A thimerosal-free hyaluronidase preparation wherein the preferred hyaluronidase enzyme is devoid of molecular weight fractions below 40,000 MW, between 60-70,000 MW and above 100,000 MW. Also disclosed is a method for accelerating the clearance of hemorrhagic blood from the vitreous humor of the eye, said method comprising the step of contacting at least one hemorrhage-clearing enzyme (e.g., a.beta.-glucuronidase, matrix metalloproteinase, chondroitinase, chondroitin sulfatase or protein kinase) with the vitreous humor in an amount which is effective to cause accelerated clearance of blood therefrom. Excerpt(s): The present invention relates generally to enzyme preparations for therapeutic administration to the eyes of humans or other mammals, and more particularly to a) a method for utilizing one or more enzymes to accelerate the rate at which hemorrhagic blood is cleared from the vitreous body of the mammalian eye and b) an improved hyaluronidase preparation for ophthalmic administration. In human beings, the anatomy of the eye includes a "vitreous body" which occupies approximately four fifths of the cavity of the eyeball, behind the lens. The vitreous body is formed of gelatinous material, known as the vitreous humor. Typically, the vitreous humor of a normal human eye contains approximately 99% water along with 1% macromolecules including; collagen, hyaluronic acid, soluble glycoproteins, sugars and other low molecular weight metabolites. The retina is essentially a layer of nervous tissue formed on the inner posterior surface of the eyeball. The retina is surrounded by a layer of cells known as the choroid layer. The retina may be divided into a) an optic portion which participates in the visual mechanism, and b) a non-optic portion which does not participate in the visual mechanism. The optic portion of the retina contains the rods and cones, which are the effectual organs of vision. A number of arteries and veins enter the retina at its center, and splay outwardly to provide blood circulation to the retina. Web site: http://appft1.uspto.gov/netahtml/PTO/search-bool.html
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Identification and uses of a hyaluronan receptor for endocytosis Inventor(s): Weigel, Janet; (Edmond, OK), Weigel, Paul H.; (Edmond, OK), Zhou, Bin; (Edmond, OK) Correspondence: Dunlap Codding & Rogers P.C.; Suite 420; 9400 N. Broadway; Oaklahoma City; OK; 73114; US Patent Application Number: 20020197681 Date filed: April 25, 2001 Abstract: A purified nucleic acid segment encoding a functionally active HARE or an active peptide fragment thereof, and methods for producing functionally active HARE or an active peptide fragment thereof therefrom, wherein the functionally active HARE or an active peptide fragment thereof is able to specifically bind HA, chondroitin and chondroitin sulfate. Excerpt(s): This application claims the benefit of U.S. Provisional Application Serial No. 60/245,320, filed Nov. 2, 2000, and U.S. Provisional Application Serial No. 60/199,538, filed Apr. 25, 2000. The present invention generally relates to a HA Receptor for Endocytosis, and more particularly, but not by way of limitation, to methods of purifying such HA Receptor for Endocytosis. HA, also referred to herein as hyaluronic acid, or hyaluronan, is an important and often abundant extracellular matrix component of all tissues, in particular cartilage, skin and vitreous humor (Evered and Whelan, The Biology of Hyaluronan, Ciba Fnd. Symposium, 143:1 (1989)). HA plays a key role in development, morphogenesis and differentiation, in cell adhesion and proliferation, and in inflammation and wound healing (Evered and Whelan, The Biology of Hyaluronan, Ciba Fnd. Symposium, 143:1 (1989); Toole, J. Intern. Med. 242:35 (1997); Knudson and Knudson, FASEB J. 7:1233 (1993); Laurent and Fraser, FASEB J. 6:2397 (1992)). In humans, the total body turnover of HA is several grams per day (Evered and Whelan, The Biology of Hyaluronan, Ciba Fnd. Symposium, 143:1 (1989)). Although local turnover of HA occurs in avascular tissues, particularly cartilage (Hua et al, J. Cell Sci. 106:365 (1993); Aguiar et al, Exp. Cell Res. 252:292 (1999)), two major clearance systems are responsible for HA degradation and removal in the body (Laurent and Fraser, FASEB J. 6:2397 (1992)). The first is the lymphatic system, which accounts for about 85% of the HA turnover, and the second is in the liver, which accounts for the other approximately 15% of the total body HA turnover. Web site: http://appft1.uspto.gov/netahtml/PTO/search-bool.html
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In vitro formation of congophilic maltese-cross amyloid plaques to identify antiplaque therapeutics for the treatment of Alzheimer's and Prion diseases Inventor(s): Castillo, Gerardo; (Seattle, WA), Snow, Alan D.; (Lynnwood, WA) Correspondence: Patrick M. Dwyer; Proteotech, INC.; Suite 114; 1818 Westlake Avenue N; Seattle; WA; 98109; US Patent Application Number: 20020168753 Date filed: November 30, 2001 Abstract: Co-incubation of an amyloid protein with sulfated macromolecules as a method for the formation of amyloid plaques. The amyloid protein may be the betaamyloid protein or the prion protein or the like. Amyoid plaque formation in one embodiment proceeds in vitro and desireably produces amyloid plaques that stain with
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Congo red and demonstrate a maltese-cross pattern when viewed under polarized light. The method also produces amyloid plaques that demonstrate an "amyloid star" appearance when viewed by transmission electron microscopy.Sulfated macromolecules include a sulfated proteoglycan selected from the group consisting of perlecan,.about.220 kilodalton heparan sulfate proteoglyean, glypican, cerebroglycan, aggrecan, synaptoglycan (SV2PG), syndecan, N-syndecan (also known as syndecan-3), syndecan-1, syndecan-4, neurocan, phosphacan, decorin, biglycan, versican, amphiglycan, lumican, PG-M, PG-M (3), agrin, betaglycan, claustrin, brevican, appican, epican, neuroglycan-C, and fragments thereof. Thw sulfated macromolecule may be a sulfated glycosaminoglycan selected from the group consisting of heparin, heparan sulfate, dermatan sulfate, chondroitin sulfate, keratan sulfate, and fragments thereof.An in vivo assay is also presented for selecting a candidate therapeutic agent for inhibiting or disrupting amyloid plaque deposition or persistence. The assay includes a) preforming congophilic maltese-cross amyloid plaques in vitro following incubation of an amyloid protein and a selected sulfated macromolecule, b) using a first cannula and osmotic pump to continuously infuse for a selected duration the pre-formed congophilic maltese-cross amyloid plaques into a tissue or organ, c) changing the first cannulae and osmotic pump with a second cannulae and osmotic pump to administer the candidate therapeutic, and d) detecting the candidate therapeutic's ability to disrupt, reduce, or eliminate congophilic maltese-cross amyloid plaque deposition/persistence in the tissue or organ. Excerpt(s): This application is a continuation of Ser. No. 09/267,795 filed Mar. 12, 1999, which claims priority to provisional application No. 60/077,924 filed Mar. 13, 1998. The invention relates to methods of formation of particular amyloid plaques and to diagnostic and therapeutic applications for such plaques in the treatment of Alzheimer's and Prion Diseases. Alzheimer's disease is characterized by the accumulation of a 39-43 amino acid peptide termed the beta-amyloid protein or A.beta., in a fibrillar form, existing as extracellular amyloid plaques and as amyloid within the walls of cerebral blood vessels. Fibrillar A.beta. amyloid deposition in Alzheimer's disease is believed to be detrimental to the patient and eventually leads to toxicity and neuronal cell death, characteristic hallmarks of Alzheimer's disease. A variety of morphologically distinct types of A.beta.-containing plaques have been described in the brains of Alzheimer's disease patients including diffuse plaques (which demonstrate A.beta. immunoreactivity but do not stain for fibrillar amyloid using amyloid stains such as Congo red and Thioflavin S), neuritic plaques (which contain a central amyloid core which stains with Congo red and Thioflavin S, and which is surrounded by dystrophic neurites) and compact, burned-out or "amyloid star" plaques (which usually demonstrate a maltese-cross pattern when stained with Congo red and viewed under polarized light). Investigators have hypothesized that in Alzheimer's disease there is most likely a conversion from the diffuse plaque to the neuritic plaque to the compact, burned-out plaque. However, the mechanism of this conversion and the essential components involved have never been elucidated. In addition, the formation of compact plaques in vitro which demonstrate a maltese-cross pattern when stained with Congo red and viewed under polarized light has never been achieved. Web site: http://appft1.uspto.gov/netahtml/PTO/search-bool.html
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Inhibitors of glycosaminoglycans Inventor(s): Mummert, Mark E.; (Dallas, TX), Takashima, Akira; (Coppel, TX) Correspondence: Bozicevic, Field & Francis Llp; 200 Middlefield RD; Suite 200; Menlo Park; CA; 94025; US Patent Application Number: 20030054991 Date filed: March 20, 2002 Abstract: The present invention provides peptide derivatives with a specific affinity for glycosaminoglycan molecules. These peptide derivatives include multimers as well as chemically modified peptides and may be prepared by a variety of methods. The peptides of the invention have numerous functions, including but not limited to use as inhibitors of glycosaminoglycan-mediated signaling events and targeting agents. Peptides of the invention may be directed against any glycosaminoglycan, including hyaluronic acid, chondroitin sulfate A, chondroitin sulfate C, dermatan sulfate, heparin, keratan sulfate, keratosulfate, chitin, chitosan 1, and chitosan 2. The peptide derivatives of the invention also have therapeutic uses in the treatment and prevention of diseases involving inflammatory diseases, cancer, and cancer metastasis, autoimmune diseases, etc. Excerpt(s): This application is a continuation-in-part application of U.S. patent application Ser. No. 09/532,709 entitled MODULATORS OF POLYSACCHARIDES AND USES THEREOF, filed Mar. 22, 2000 and claims priority to U.S. provisional Patent Application No. 60/277,790 entitled "INHIBITORS OF GLYCOSAMINOGLYCANS" filed Mar. 21, 2001 and the disclosures of these applications are hereby incorporated by reference in their entirety into this application for all purposes. The present invention relates generally to the fields of cancer, immunology and inflammatory diseases. More particularly, it concerns peptide inhibitors of glycosaminoglycans. The invention also provides therapeutic and preventive methods for the treatment of inflammatory diseases, autoimmune diseases and other glycosaminoglycan-associated diseases. Additionally, the invention provides anticancer therapies using glycosaminoglycan binding agents. Interactions of cells of the immune system with components of the extracellular matrix (ECM) are responsible for the induction of various immune responses including inflammatory responses. In addition to being an important component of the extracellular structure, the ECM also is involved in cellular signal transduction events by interactions with cellular receptors. Thus, the ECM modulates cell adhesion, cell proliferation, cell differentiation, etc. (Schubert et al. Trends Cell. Biol., 2:63-66, 1992). Major constituents of the ECM include glycosaminoglycans, fibronectin, laminin, collagens, and proteoglycans, which bind specific cell surface receptors via protein-protein and protein-carbohydrate interactions. The glycosaminoglycans are linear polymers of repeating disaccharides often bound covalently to a protein core. Web site: http://appft1.uspto.gov/netahtml/PTO/search-bool.html
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Injectable solution containing a shark-derived chondroitin sulfate iron colloid Inventor(s): Katayama, Naohisa; (Osaka, JP), Katsumata, Takashi; (Osaka, JP), Nishida, Seiji; (Osaka, JP), Sato, Makoto; (Osaka, JP) Correspondence: Kubovcik & Kubovcik; Suite 710; 900 17th Street NW; Washington; DC; 20006 Patent Application Number: 20030118666 Date filed: October 10, 2002 Abstract: An injectable solution comprising a shark-derived chondroitin sulfate iron colloid, and a method for manufacturing an injectable solution comprising the step of adding an aqueous ferric salt solution and an aqueous alkali metal hydroxide solution to a shark-derived chondroitin sulfate solution, such that the resulting mixture has a pH value adjusted to any pH value within the range of from about 5.5 to about 7.5. Excerpt(s): The present invention relates to an iron preparation capable of preventing and treating the symptoms of iron-deficiency anemia in humans and mammals. More specifically, the present invention relates to an injectable solution with excellent safety and pharmaceutical stability for the supply of chondroitin sulfate iron colloid. Iron is one of essential metallic nutrients for humans and mammals. If a deficiency of iron is caused by an insufficient uptake of iron by oral administration, bleeding, or the like, the supply of iron becomes absolutely indispensable. When iron is parenterally supplied, there is a problem in terms of toxicity because an ionic iron compound binds to transferrin and also binds to plasma protein, causing shock or the like. Thus, there is a need to devise the supplying of iron in a colloidal form with less side effects. For an iron ion to be parenterally supplied to humans, ferric chloride is used in general. In a solution, such ferric chloride exists as a ferric hydroxide colloid particle. Such a colloid particle includes oxy chloride (FeOCl) in addition to ferric oxide (Fe.sub.2O.sub.3) and water, and oxy chloride dissociates to FeO.sup.+ and Cl.sup.-. As a result, the colloid particle becomes a hydrophobic colloid, which is positively charged and has a tendency to aggregate. If the pH value thereof rises to about 3 or more, it will precipitate out of solution as a result of the aggregation ("Colloid Chemistry", written by B. Jirgensons et al., and translated under the editorship of Fumikazu Tamamushi, Baifukan, Tokyo, 1967, Japan). Heretofore, an iron hydroxide colloid solution in which dextran is used as a protective colloid has been used in the United States, while iron-poly(sorbitol gluconic acid) complex salt has been used in Europe (Goodman and Gilman: The Pharmacological Basis of Therapeutics, MacMillan, NewYork 1980, pp. 1325-1326). In japan, on the other hand, an iron colloid solution, in which chondroitin sulfate having a high iron utilization ratio and less side effects is used as a protective colloid, has been used. For example, in Japan, chondroitin sulfate iron colloid is commercially available as an intravenous injection preparation for iron deficiency anemia, Blutal (trade name, Dainippon Pharmaceutical Co., Ltd. Japan). In addition, a preparation containing chondroitin sulfate iron colloid as a supplement of essential trace elements of total parenteral nutrition is also commercially available as Elemenmic injection, Elemate injection (trade names, Ajinomoto Pharma, Co., Ltd. Japan), Mineralin injection, Parmirin injection (trade names, Nippon Pharmaceutical Co., Ltd. Japan/Takeda Chemical Industries, Ltd. Japan), Elemeal injection (trade name, Sawai Pharmaceutical, Co., Ltd. Japan), and Volvix injection (trade name, Fujiyakuhin Co., Ltd. Japan/Yakult Honsha Co., Ltd. Japan). Web site: http://appft1.uspto.gov/netahtml/PTO/search-bool.html
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Low molecular weight chondroitin sulphate compound having cosmetic activity Inventor(s): Delannoy, Charles; (Wimereux, FR), Durand, Patrick; (Reze, FR), Landrein, Annie; (Nantes, FR), Roy, Philippe; (Nantes, FR) Correspondence: Jacobson Holman; Professional Limited Liabilty Company; 400 Seventh Street, N.W.; Washington; DC; 20004; US Patent Application Number: 20030032620 Date filed: July 25, 2001 Abstract: The invention relates to a low molecular weight chondroitin sulphate compound having cosmetic activity, characterised more particularly by efficient incorporation in vitro of thymidine, glucosamine and leucine in fibroblast macromolecules of the human cutis. Local application of this compound stimulates fibroblast metabolism. The invention also relates to a method of preparing the said compound. Excerpt(s): The constituents of the extracellular matrix of the skin are divided among various categories mainly comprising laminin, the various kinds of collagens, elastin, fibronectin and various proteoglycanes, the main ones being heparan sulphate and chondroitin sulphates. These proteoglycanes (J. T. Gallagher, 1989. Current Biol., 1, 1201) comprise a protein part on to which glycosylated chains with repeating units called glycosaminoglycans (GAG) are grafted. Depending on the type of skin (phanerogenic or glabrous) their distribution may be heterogeneous or homogeneous. They also occur as constituents of the plasmic membrane and some are directly associated with the collagen fibrils. Owing to their negative charges, they produce an environment round them capable of trapping ions, water and various metabolites. GAG chains also perform an essential function owing to their affinity for circulating growth factors. Chondroitin sulphates (CS) are usually obtained from animal cartilage or skins and are characterised by the presence of a sulphate group on the disaccharide unit. Industrially, CS are obtained mainly from avian, ovine, bovine, porcine and shark cartilages. In view of the risk of bovine spongiform encephalopathy, bovine and ovine cartilages are no longer used to a significant extent. It is also likely that in the near future a larger number of shark species will be classed as protected species. Web site: http://appft1.uspto.gov/netahtml/PTO/search-bool.html
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Materials and methods for nerve repair Inventor(s): Muir, David F.; (Gainesville, FL) Correspondence: Saliwanchik Lloyd & Saliwanchik; A Professional Association; 2421 N.W. 41st Street; Suite A-1; Gainesville; FL; 326066669 Patent Application Number: 20030072749 Date filed: August 13, 2002 Abstract: The subject invention pertains to compositions and methods for promoting repair of damaged nerve tissue. The compositions and methods of the subject invention can be employed to restore the continuity of nerve interrupted by disease, traumatic events or surgical procedures. Compositions of the subject invention comprise one or more chondroitin sulfate proteoglycan (CSPG)-degrading enzymes that promote axonal penetration into damaged nerve tissue. The invention also concerns methods for promoting repair of damaged nerve tissue using the present compositions and nerve
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tissue treated according to such methods. The invention also pertains to kits for nerve repair. Excerpt(s): Peripheral nerve injuries are a major source of chronic disability. Poor management of nerve injuries is associated with muscle atrophy and can lead to painful neuroma when severed axons are unable to reestablish continuity with the distal nerve. Although nerves have the potential to regenerate after injury, this ability is strictly dependent upon the regenerating nerve fibers (and their axonal sprouts) making appropriate contact with the severed nerve segment (and the Schwann cell basal laminae therein). Regenerating axons that fail to traverse the gap or injury site and enter the basal lamina of the severed distal nerve segment will deteriorate, resulting in neuronal death, muscle atrophy and permanent functional deficit (Fawcett J W et al. [1990] Annu Rev Neurosci 13:43-60). Briefly, a nerve carries the peripheral processes (or axons) of neurons. The neuronal cell bodies reside in the spinal cord (motor neurons), in ganglia situated along the vertebral column (spinal sensory ganglia) or in ganglia found throughout the organs of the body (autonomic and enteric ganglia). A nerve consists of axons, Schwann cells and extensive connective tissue sheaths (Dagum A B [1998] J Hand Ther 11:111-117). The outer covering, the epineurium, is made of collagenous connective tissue that cushions the fascicles from external pressure and surrounds the perineurium. The perineurium surrounds the individual fascicles and, together with endothelial cells in the endoneurial microvessels, functions as the blood-nerve barrier. The endoneurium lies inside the perineurium and consists of collagenous tissue that surrounds the Schwann cells and axons. A fascicular group consists of two or more fascicles surrounded, respectively, by perineurium and epineurium. The topography of nerves is constant distally, with a group of fascicles being either sensory or motor. The neuron consists of a soma (cell body) and an axon, which can be several feet long. In nerve injuries where there is axonal disruption, but the continuity of the endoneurial sheath remains intact (e.g., crush injury), axons regenerate within their original basal lamina and complete recovery can be expected. In contrast, axonal regrowth may be severely compromised after nerve transection and surgical repair is highly dependent on the realignment of the nerve elements described above (Dagum A B [1998] J Hand Ther 11:111-117). Epineurial coaptation (neurorrhaphy) is the primary method of dealing with nerve transection. However, the extent of regeneration is highly variable and, at best, partial recovery of function can be expected (Terzis J K et al. [1990] The Peripheral Nerve: Structure, function and reconstruction, Hampton Press, Norfolk). Full restoration of function after repair of nerve transection remains an unobtainable ideal because of the fine microstructure of nerves and an inability to achieve precise axon-to-axon coaptation, despite the current state of the art in microsurgical techniques. Web site: http://appft1.uspto.gov/netahtml/PTO/search-bool.html •
Method and compositions for the treatment and prevention of pain and inflammation with a cyclooxygenase-2 selective inhibitor and chondroitin sulfate Inventor(s): Kundel, Susan; (Basel, CH), Pulaski, Steven P.; (Branchburg, NJ) Correspondence: Charles E. Dunlap; Keenan Building, Third Floor; 1330 Lady Street; Columbia; SC; 29201; US Patent Application Number: 20030114416 Date filed: August 9, 2002 Abstract: A method of treating, preventing, or inhibiting pain, inflammation or inflammation-associated disorder in a subject in need of such treatment or prevention
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provides for treating the subject with chondroitin sulfate and a cyclooxygenase-2 selective inhibitor, or a prodrug thereof, wherein the amount of chondroitin sulfate and the amount of a cyclooxygenase-2 selective inhibitor or a pharmaceutically acceptable salt or prodrug thereof together constitute a pain or inflammation suppressing treatment or prevention effective amount. Glucosamine can optionally be present. Compositions that contain the combination of chondroitin sulfate and cyclooxygenase-2 selective inhibitor and, optionally, the glucosamine, are disclosed, as are pharmaceutical compositions. Excerpt(s): The present application claims the benefit of U.S. Provisional Application Serial No. 60/312,211 filed Aug. 14, 2001, which is incorporated herein by reference thereto. The present invention relates to methods for the treatment and prevention of pain and inflammation and compositions for such treatment, and more particularly to methods for the treatment and prevention of pain and inflammation in subjects needing such treatment and prevention and to compositions comprising a cyclooxygenase-2 selective inhibitor that are useful in such methods. Inflammation is a manifestation of the body's response to tissue damage and infection. Although the complex mechanisms of inflammation are not fully elucidated, inflammation is known to have a close relationship with the immune response and to be associated with pain and fever in the subject. Web site: http://appft1.uspto.gov/netahtml/PTO/search-bool.html •
Method for reducing malodor of chondroitin Inventor(s): Ebube, Nkere Kanu; (Glen Allen, VA), Mark, William Antonio; (Mechanicsville, VA) Correspondence: Wyeth; Patent Law Group; Five Giralda Farms; Madison; NJ; 07940; US Patent Application Number: 20020141963 Date filed: March 8, 2002 Abstract: The present invention relates to a method of removing or masking odor associated with chondroitin derived from marine life. The method comprises blending the chondroitin with citric acid, silicon dioxide, and optionally a flavorant to yield a substantially non-malodorous blend. Excerpt(s): This application claims priority from copending provisional application Serial No. 60/274806, filed Mar. 9, 2001, the entire disclosure of which is hereby incorporated by reference. The present invention relates to a method for the removal or masking of malodor from chondroitin derived from marine life. The present invention also relates to chondroitin compositions derived from marine life which lack a malodor. Chondroitin and glucosamine are chondroprotective agents used for the treatment of osteoarthritis and related diseases. Chondroitin sulfate is a soluble mucopolysaccharide derived from bovine, ovine or shark cartilage. Chondroitin sulfate derived from marine life, such as cartilage isolated from sharks, provides a rich, pure, and readily absorbed source of chondroitin. Web site: http://appft1.uspto.gov/netahtml/PTO/search-bool.html
Patents 191
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Method of using hydroxycarboxylic acids or related compounds for treating skin changes asociated with intrinsic and extrinsic aging Inventor(s): Van Scott, Eugene J.; (Abington, PA), Yu, Ruey J.; (Ambler, PA) Correspondence: Akin, Gump, Strauss, Hauer & Feld, L.L.P.; One Commerce Square; 2005 Market Street, Suite 2200; Philadelphia; PA; 19103; US Patent Application Number: 20030083380 Date filed: December 6, 2000 Abstract: A composition comprising an amphoteric or pseudo-amphoteric agent and a polyhydroxy alpha hydroxyacid existing as a free acid, lactone, or salt, and isomeric or non-isomeric forms thereof is provided. The amphoteric or pseudo-amphoteric agent can be selected from amino acids, dipeptides, aminoaldonic acid, aminouronic acid, lauryl aminoproplyglycine, aminoaldaric acid, neuraminic acid desulfated heparin, deacetylated hyaluronic acid, hyalobiuronic acid, chondrosine, deacetylated chondroitin, creatine, creatinine, hydroxyproline, homocysteine, homocystine, homoserine, ornithine, citrulline, phosphatidylserine, and sphingomyelin. The composition may contain other additives, including cosmetic or pharmaceutical agents for topical treatment of dermatological disorders. Excerpt(s): This invention relates generally to therapeutic treatment as well as preventive measures for cosmetic conditions and dermatologic disorders by topical administration of amphoteric compositions or polymeric forms of alpha hydroxyacids, alpha ketoacids and related compounds. We initially discovered that alpha hydroxy or keto acids and their derivatives were effective in the topical treatment of disease conditions such as dry skin, ichthyosis, eczema, palmar and plantar hyperkeratoses, dandruff, acne and warts. We have now discovered that amphoteric compositions and polymeric forms of alpha hydroxyacids, alpha ketoacids and related compounds on topical administration are therapeutically effective for various cosmetic conditions and dermatologic disorders. In our prior U.S. Pat. No. 3,879,537 entitled "Treatment of Ichthyosiform Dermatoses" we described and claimed the use of certain alpha hydroxyacids, alpha ketoacids and related compounds for topical treatment of fish-scale like ichthyotic conditions in humans. In our U.S. Pat. No. 3,920,835 entitled "Treatment of Disturbed Keratinization" we described and claimed the use of these alpha hydroxyacids, alpha ketoacids and their derivatives for topical treatment of dandruff, acne, and palmar and plantar hyperkeratosis. Web site: http://appft1.uspto.gov/netahtml/PTO/search-bool.html
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Nutritional composition for the treatment of connective tissue Inventor(s): Petito, Anita M.; (Bethlehem, PA), Petito, George D.; (Bethlehem, PA) Correspondence: Richard C. Litman; Crystal City Station; P.O. Box 15035; Arlington; VA; 22215-0035; US Patent Application Number: 20030069171 Date filed: November 5, 2002 Abstract: A nutritional composition for the treatment of connective tissue in mammals which includes a glucosamine salt, chondroitin sulfate, collagen and sodium hyaluronate which synergistically act as a chondroprotective agent. The composition can further include a detoxifying agent, an anti-inflammatory agent or an analgesic to
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demonstrate additional therapeutic and physiologic properties. The nutritional composition acts as a chondro-protective agent which provides foundational support for the creation of new body tissue and cartilage growth in humans and animals. Excerpt(s): This application is a continuation-in-part of application Ser. No. 09/360,169 filed Jul. 26, 1999, which is a continuation-in-part of application Ser. No. 09/046,710 filed Mar. 24, 1998, and now abandoned. The present invention relates to therapeutic compositions which provide for the treatment of connective tissue in mammals and, more particularly to nutritional compositions capable of acting as chondroprotective agents, as well as exhibiting added pharmacological properties. The related art of interest discloses numerous pharmaceutical compositions and methods for the treatment of connective tissue in humans and animals. For example, U.S. Pat. No. 4,837,024 issued on Jun. 6, 1989, to Dov Michaeli describes topical compositions for improving wound healing comprising a suspension of particles of collagen and a glycosaminoglycan. The composition is taught to be useful for treating surface wounds by applying the composition to a gauze, bandage or the like. Web site: http://appft1.uspto.gov/netahtml/PTO/search-bool.html •
Ophthalmic medicament Inventor(s): Neuhann, Tobias; (Munich, DE) Correspondence: Ostrolenk Faber Gerb & Soffen; 1180 Avenue OF The Americas; New York; NY; 100368403 Patent Application Number: 20020081289 Date filed: September 14, 2001 Abstract: According to the invention, a novel ophthalmic medicament is made available, which contains in aqueous solution or suspension at least one carbohydrate, at least one amino acid, at least one electrolyte, a chondroitin sulfate and optionally further customary excipients. Excerpt(s): The invention relates to a novel ophthalmic medicament which can be employed in a large number of eye diseases and in particular in accompaniment to corneal transplantation and in refractive corneal surgery. Although novel ophthalmic medicaments are continually being developed and also just recently a number of highly active ophthalmic medicaments have been developed for all sorts of eye diseases, for a number of eye diseases there are still no satisfactory medicaments or a satisfactory action can only be achieved using steroidal medicaments which contain such a high dose of steroids that they exhibit a number of side effects, for example an intraocular pressure increase. Especially recently, refractive corneal surgery such as, in particular, Lasik has been used for the elimination of amblyopia. There are presently no satisfactory opthalmic medicaments for concomitant treatment and in particular for after-treatment in the case of refractive corneal surgery. Web site: http://appft1.uspto.gov/netahtml/PTO/search-bool.html
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Patch for the delivery of topical agents Inventor(s): Hayes, Harry; (Hampden, MA), Young, Tyler F.; (Hampden, MA) Correspondence: Kevin H. Vanderleeden; Mccormick, Paulding & Huber Llp; 185 Asylum Street, Cityplace II; Hartford; CT; 06103; US Patent Application Number: 20030180347 Date filed: March 13, 2003 Abstract: The adhesive patch for the delivery of topical agents to the skin including a polymer matrix, generally a hydrogel matrix having adhesive properties, a skin conditioner and a penetration enhancer. The hydrogel matrix including purified water, glycerin, polyacylate, sorbitol, kaolin, CMC (carboxymethyl cellulose), alcohol, castor oil, TWEEN 80 (polyoxyethylene sorbitan monooleate), fragrance and citric acid. Skin conditioners and penetration enhancers including methyl sulfonyl methane, glucosamine and chondroitin. The matrix may also include a topically effective drug. The adhesive patch includes a support backing of non-woven material or a nonocclusive film and a protective film covering the polymer matrix. Excerpt(s): This application claims the benefit of U.S. Provisional Application Serial No. 60/365,193, filed on Mar. 19, 2002. The present invention relates to a patch for the delivery of topical agents to the skin. In particular, the present invention involves a patch that utilizes a polymer matrix containing an adhesive, a skin conditioner, a penetration enhancer, and, optionally, a topically effective drug. The polymer matrix facilitates the slow diffusion of the topical agents' active ingredients over a period of time. Additionally, the polymer matrix provides adhesion such that the topical agents are kept in contact with the skin for a period of time sufficient for the agents to be effective. The delivery of topical agents to the skin may be desirable to improve the health and appearance of skin and alleviate conditions such as psoriasis, dry skin, blemishes, abrasions, cuts, or rashes. If such skin conditions are not treated, further damage may occur leading to infections and other maladies. Additionally, the treatment of chronic or acute pain often involves the topical application of an anesthetic such as lidocaine or benzocaine. Web site: http://appft1.uspto.gov/netahtml/PTO/search-bool.html
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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.
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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 •
Preparations and method of producing the same Inventor(s): Higashi, Kiyotsugu; (Osaka-shi, JP), Iida, Kentaro; (Osaka-shi, JP), Miura, Chikara; (Osaka-shi, JP), Nishimori, Tomoharu; (Osaka-shi, JP), Onaka, Yukiko; (Osakashi, JP) Correspondence: Wenderoth, Lind & Ponack, L.L.P.; 2033 K Street N. W.; Suite 800; Washington; DC; 20006-1021; US Patent Application Number: 20020099032 Date filed: November 8, 2001 Abstract: Incorporation of an aminosugar (e.g., glucosamine) to a preparation make a vitamin B1 stable. The content of the aminosugar is an effective amount to stabilize the vitamin B1, and is, for example, not less than 0.1 part by weight relative to 1 part by weight of the vitamin B1. Incorporation of the aminosugar can improve the disintegrativity of a solid preparation comprising a glycosaminoglycan (a hyaluronic acid, a chondroitin or a salt thereof). The content of aminosugars is not less than 0.1 part by weight relative to 1 part by weight of glycosaminoglycans. The solid preparation can inhibit forming gel masses of glycosaminoglycan and can improve the disintegrativity. Moreover, a joint disorder such as arthralgia can be improved by combination of the vitamin B1 and the glucosamine (e.g., glucosamine or a salt thereof). Excerpt(s): This invention relates to a preparation in which a vitamin B1 is stabilized, particularly a preparation (particularly, a solid preparation) improved in disintegrativity (disintegration properties) as well as stabilization of the vitamin B1. This invention further relates to a composition for preventing or treating a joint disorder, which comprises a vitamin B1 and an aminosugar (especially, a glucosamine), if necessary, a glycosaminoglycan. Many pharmaceutical preparations comprising vitamin B1 are commercially available. Concretely, a vitamin B1 is utilized for Wernicke's encephalopathy, peripheral neuropathy (peripheral nervous system disorder), central neuropathy (central nervous system disorder), neuralgia, myalgia, arthralgia (lumbagia, stiff shoulder, frozen shoulder), numbness of hands and feet, therapy of asthenopia, constipation, nutrition, etc. A vitamin B1 is effective in arthralgia, however effective in relatively slight symptom of arthralgia. The joints (of human and animals) are
Patents 195
constantly subjected to stress and strain from mechanical forces that can result in a joint disorder such as arthralgia, arthritis, osteoarthritis, and stiffness. The causes of a joint disorder include various kinds such as a joint deformation, bacterium infection (microbism), virus infection, injury, immuno-disease such as allergy, rheumatism and dysbolism caused by nephritis. An inflammatory disorder such as arthriris is caused so that a patient suffers from arthralgia and joint stiffness can not maintain normal joint flexibility and mobility, and comfortable joint movement is disturbed by a joint pain and stiffness. Therefore, more effective composition for prevention and treatment of a joint disorder is required. Web site: http://appft1.uspto.gov/netahtml/PTO/search-bool.html •
Process for the preparation of chondroitin sulfates from K4 polysaccharide and obtained products Inventor(s): Oreste, Pasqua; (Milan, IT), Zoppetti, Giorgio; (Milan, IT) Correspondence: Morgan & Finnegan, L.L.P.; 345 Park Avenue; New York; NY; 101540053; US Patent Application Number: 20030100534 Date filed: October 21, 2002 Abstract: New process for the preparation of chondroitin sulfates from the bacterial origin polysaccharide named K4, by defructosilation followed by selective sulfation. Excerpt(s): The chondroitin sulfates are natural products present in animal tissues with structural and physiological functions. The chondroitin sulfates have antiinflammatory activity, they have been classified as SYSADOA (Symptomatic Slow Acting Drug Osteoarthritis) and used in the medium-long term therapy in the treatment of arthritic patients (Morreale P., Manopulo R., Galati M., Boccanera L., Saponati G. and Bocchi L. "Comparison of the antiinflammatory efficacy of chondroitin sulfate and diclofenac sodium in patients with knee osteoarthritis". J. Rheumatol., 23,1385-1391,1996). The commercial chondroitin sulfates are obtained by extraction methods from animal tissues and consist of regular disaccharides formed by glucuronic acid and Nacetylgalactosamine sulfated in position 4 and/or 6 (YOSHIDA, K. et al.--Analytical Biochemistry, 177, pp. 327-332 (1989)). Web site: http://appft1.uspto.gov/netahtml/PTO/search-bool.html
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Processes for making cryopreserved composite living constructs and products resulting therefrom Inventor(s): Laufer, Alla; (Brooklyn, NY), Ray, Nitya G.; (East Hanover, NJ), Song, Ying; (Franklin Park, NJ), Tai, Hsin-Chien; (Hackensack, NJ) Correspondence: Ralph T. Lilore; 1425 Broad Street; Clifton; NJ; 07013; US Patent Application Number: 20020123809 Date filed: December 26, 2001 Abstract: Processes are described for making a cryopreserved Composite Living Construct (CCLC) as well as a corresponding thawed and rinsed CCLC, comprised of separated layers of cultured fibroblasts and cultured keratinocytes, wherein the percent of cells that are viable, i.e., the cell viability, of such CCLC is at least about70 %. The
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viable cell density in the CCLC is at least about 50% of that before cryopreservation. The storage stability of the CCLC is at least about 12 months. Additionally, the metabolic activity of thawed and rinsed CCLC is at least about 50% of the Composite Living Construct (CLC) before cryopreservation. The structural integrity of CCLC is substantially the same as the CLC before cryopreservation. The process for making the CCLC comprises the steps of: providing a collagen substrate comprised of a collagen sponge layer and a nonporous to cells, semipermeable collagen layer; seeding and culturing, in the presence of a cell growth medium, fibroblasts on and within the collagen sponge layer and keratinocytes on the nonporous to cells, semipermeable collagen layer, thereby providing a CLC; equilibrating the CLC, according to a defined equilibration program with a cryoprotectant solution comprising at least chondroitin sulfate and dimethylsulfoxide; lowering the temperature, according to a programmed rate, to about -90.degree. C.; and storing the CCLC at about -150.degree. C. or lower. The process for preparing the CCLC to treat wounds in humans and in animals additionally comprises programmed thawing as well as a rinsing sequence to substantially remove the cryoprotectants. Excerpt(s): The present invention relates to cryopreserved Composite Living Constructs (CCLCs) which are comprised of separated layers of cultured fibroblasts and cultured keratinocytes and to processes for making CCLCs. The CCLCs are prepared from composite living constructs (CLCs) by equilibrating with cryoprotectant solutions, freezing, and storing at cryogenic temperatures. Prior to use, they are thawed and rinsed to substantially remove the cryoprotectants. CLCs are biologically active composite living constructs that are useful as wound dressings some of which comprise both a fibroblast dermal layer and an epidermal layer of keratinocytes usually on and/or in a matrix. CLCs may be employed for and aid in the regeneration of tissue in wounds that are denuded of skin such as granulating wounds, injuries such as those found in abrasions, excisions, burns and dystrophic epidermolysis bullosa and in ischemic skin such as that present in individuals suffering from decubitus, diabetic, and venous stasis ulcers. The viability of CLCs as well as those of other cell constructs, such as skin equivalents, grafts, vessels, organs, etc., is short-lived unless such constructs are cryopreserved. Stability of stored cells and constructs are typically limited to about 24 to 120 hours unless they are protected from deterioration by some means such as cryopreservation. A primary goal of cryopreservation is to extend the storage stability of the CLCs without substantially compromising viability and metabolic activity as well as to permit them to maintain such viability and resume metabolic activity upon thawing and rinsing. "Storage stability" is the total time that a CCLC can be stored while minimally compromising viability and metabolic activity upon thawing and rinsing. Long storage stability is important for transplants or implants to be practical and commercially useful, to accommodate shipping and storage schedules, and to maintain sustainable inventories. Measurements useful in assessing the quality of the CCLC that is achieved by cryopreservation are: "construct cell density", the total number of viable cells per unit area; "cell viability", the percent of the total number of cells that are viable; and "metabolic activity", a measure of the overall vigor of the viable cells in terms of their ability to metabolize nutrients and perform other cell maintenance functions. Additional measurements that may be applied to this invention are histologic examination of the structure of the CCLC for the presence, configuration, and distribution of cells within and on the construct, and the ability of the cells and constructs to express wound-healing and tissue regeneration promoters such as growth factors and cytokines. Web site: http://appft1.uspto.gov/netahtml/PTO/search-bool.html
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Product and method for treating joint disorders in vertebrates Inventor(s): Chrisope, Gerald L.; (Boulder, CO), Rose, Rebecca; (Longmont, CO) Correspondence: Sheridan Ross PC; 1560 Broadway; Suite 1200; Denver; CO; 80202 Patent Application Number: 20020064568 Date filed: January 8, 2002 Abstract: A compound and method of using such compound is disclosed that, when administered to an animal, is capable of arresting the inflammatory response in affected tissues and facilitates the repair and maintenance of damaged tissues in the joints of vertebrates. The combination of natural physiological metabolites and herbal phytochemicals is used to treat connective tissue diseases, the composition preferably orally administered. One embodiment of the composition includes chondroitin sulfate and glucosamine that, when ingested by a vertebrate, suppresses the degradation of connective tissue by an autoimmune response. A preferred composition of the present invention includes a palatability agent, an herbal phytochemical, and a metabolic precursor that synergistically acts to increase blood circulation, thereby enhancing transport of the phytochemical and metabolic precursors to an affected site whereby deleterious inflammatory byproducts are removed. Excerpt(s): The present application claims priority from U.S. Provisional Application Serial No. 60/013,025, filed Mar. 8, 1996. The present invention is directed to compounds, and methods using such compounds, that when administered to an animal, arrest the inflammatory response in affected tissues and facilitate repair and maintenance of damaged tissues in the joints of vertebrates. In healthy conditions, articular cartilage forms a smooth surface between articulating bone ends to reduce the friction caused by movement. This friction is further reduced by the synovial fluid. Web site: http://appft1.uspto.gov/netahtml/PTO/search-bool.html
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Salmon-origin chondroitin sulfate Inventor(s): Kono, Hiroyuki; (Hokkaido, JP), Takai, Mitsuo; (Hokkaido, JP) Correspondence: Peter F Corless; Edward & Angell; P O Box 9169; Boston; MA; 02209; US Patent Application Number: 20030162744 Date filed: December 17, 2002 Abstract: A novel chondroitin sulfate which can be produced more economically in a large amount and is expected as being useful for various purposes and processes for producing the same. Namely, a novel chondroitin sulfate which has an intermediate structure between the conventionally known whale-origin chondroitin sulfate and shark-origin chondroitin sulfate and is expected as useful for various purposes in the fields of drugs, cosmetics, food additives, etc. A process for producing the abovedescribed chondroitin sulfate comprises grinding salmon nasal cartilage at a low temperature, defatting the ground matter, then treating it with an alkali and pronase, centrifuging the thus obtained liquid digested matter and then precipitating it from ethanol; and another process wherein the precipitate thus obtained is further treated with a cation exchange resin. Excerpt(s): The present invention relates to a novel chondroitin sulfate which is expected to be useful for various purposes in the fields of drugs, cosmetics, food
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additives and the like. A chondroitin sulfate is an acid mucopolysaccharide contained in a connective tissue of animals. This is made of a disaccharide recurring structure of Dglucuronic acid and a sulfated N-acetylgalactosamine, and there are various isomers depending on sulfation of a hydroxyl group of a constituent sugar. Sites to be sulfated are hydroxyl groups in the 2- and 3-positions of glucuronic acid, a hydroxyl group in the 2-position of iduronic acid and hydroxyl groups in the 4- and 6-positions of Nacetylgalactosamine. A chondroitin sulfate chain is a linear polysaccharide having a molecular weight of 10.sup.4 to 10.sup.5, and present as a proteoglycan covalently bound to a core protein. Generally, as a chondroitin sulfate chain occurring in nature, one made only of a recurring unit of one type of a sulfated disaccharide rarely exists, and it usually contains various kinds of sulfated or non-sulfated disaccharides at different ratios. Web site: http://appft1.uspto.gov/netahtml/PTO/search-bool.html •
Skin care agent and method of skin care Inventor(s): Matahira, Yoshiharu; (Shizuoka-ken, JP), Saito, Michiko; (Shizuoka-Ken, JP) Correspondence: Frishauf, Holtz, Goodman & Chick, PC; 767 Third Avenue; 25th Floor; New York; NY; 10017-2023; US Patent Application Number: 20030003116 Date filed: April 25, 2000 Abstract: The present invention provides a skin care agent comprising Nacetylglucosamine as an active ingredient, and a method of skin care using it. The promoter is preferably in the form of tablets, capsules, powder such as dust or granules, liquid or past. The skin care agent of the present invention may be incorporated into foods such as confectioneries, powdered soup and beverages. By orally ingesting the skin care agent of the present invention, the N-acetylglucosamine as an active ingredient is rapidly absorbed, and by utilizing a part thereof as a starting material of acidic mucopolysaccharides such as hyaluronic acid or chondroitin sulfate, the moisture and tension of skin can be improved and the rough skin and fine wrinkles can be prevented or ameliorated. Excerpt(s): The present invention relates to a skin care agent (or a skin-beautification promoter) which improves moisture and tension of skin and promotes prevention and amelioration of e.g. rough skin and fine wrinkles by orally ingesting it, and a method of skin care. Acidic mucopolysaccharides such as hyaluronic acid or chondroitin sulfate have a high water retention, bond to collagen which serves as a column of intercellular substance matrix, and are mostly distributed in, for example, connective tissues, cartilaginous tissues and skin tissues, thereby being useful for keeping functions and forms of cells. In the skin tissues, the acidic mucopolysaccharides, collagen, etc. mostly exist in corium layer and take a large part in water retention and resilience of skin. It is known that when the amounts thereof decrease due to aging or the like, the water retention and resilience of skin will be lost, thereby causing rough skin, fine wrinkles, etc. Web site: http://appft1.uspto.gov/netahtml/PTO/search-bool.html
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Synergistic proteoglycan compositions for treatment of inflammatory diseases Inventor(s): Theoharides, Theoharis C.; (Brookline, MA) Correspondence: Melvin Blecher, PH.D. J.D.; Attorney AT Law; 4329 Van Ness Street, N.W.; Washington; DC; 20016-5625; US Patent Application Number: 20020176902 Date filed: January 30, 2001 Abstract: Compositions with synergistic anti-inflammatory effect in inflammatory diseases resulting from activation and consequent degranulation of mast cell and followed by secretion of inflammatory biomolecules from the activated mast cells, composed of a heavily sulfated, non-bovine proteoglycan such as chondroitin sulfate C and one or more of a hexosamine sulfate such as D-glucosamine sulfate, a flavone such as quercetin, a special organic extra virgin kernel seed olive oil, S-adenosylmethionine and diphenhydramine. Excerpt(s): The invention is generally related to the treatment of inflammatory conditions. More specifically, the invention is related to compositions containing inhibitors of mast cell activation and secretion designed to be used as dietary supplement in the treatment of inflammatory conditions. There have been a number of mostly anecdotal reports that the proteoglycan chondroitin sulfate, as well as glucosamine sulfate, a product of the intestinal breakdown of proteoglycans may be helpful in relieving the pain of osteoarthritis:--Shute N. Aching for an arthritis cure. US News and World Report, Feb. 10, 1997.--Cowley G. The arthritis cure? Newsweek, Feb. 17, 1997.--Foreman J. People, and their pets, tout arthritis remedy. The Boston Globe, Apr. 7, 1997; Tye L. Treatment gains scientific attention. The Boston Globe, Sep. 25, 2000. A recent meta-analysis showed potential therapeutic benefit of chondroitin sulfate in osteoarthritis [McAlindon et al. J Am Med Assn. 283:1469 (2000), and NIH-funded clinical trial OD-98-003 dated Oct. 10, 1997]. However, less than 5% of the chondroitin sulfate in available preparations is absorbed orally. Furthermore, such commercial preparations use chondroitin sulfate obtained from cow trachea, with the possible danger of contracting "mad cow disease" [McAlindon et al. above]. In fact, the European Union has banned even cosmetics that contain bovine-derived products. Web site: http://appft1.uspto.gov/netahtml/PTO/search-bool.html
Keeping Current In order to stay informed about patents and patent applications dealing with chondroitin, 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 “chondroitin” (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 chondroitin. You can also use this procedure to view pending patent applications concerning chondroitin. Simply go back to http://www.uspto.gov/patft/index.html. Select “Quick Search” under “Published Applications.” Then proceed with the steps listed above.
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CHAPTER 7. BOOKS ON CHONDROITIN Overview This chapter provides bibliographic book references relating to chondroitin. In addition to online booksellers such as www.amazon.com and www.bn.com, excellent sources for book titles on chondroitin 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 “chondroitin” at online booksellers’ Web sites, you may discover non-medical books that use the generic term “chondroitin” (or a synonym) in their titles. The following is indicative of the results you might find when searching for “chondroitin” (sorted alphabetically by title; follow the hyperlink to view more details at Amazon.com): •
All About Glucosamine and Chondroitin by Jack Challem (Editor), Ray Sahelian; ISBN: 0895298945; http://www.amazon.com/exec/obidos/ASIN/0895298945/icongroupinterna
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Glucosamine Sulfate and Chondroitin Sulfate by Rita Elkins (1997); ISBN: 1885670486; http://www.amazon.com/exec/obidos/ASIN/1885670486/icongroupinterna
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Glucosamine Sulfate and Chondroitin Sulfate by Dallas Clouatre; ISBN: 0879838744; http://www.amazon.com/exec/obidos/ASIN/0879838744/icongroupinterna
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User's Guide to Glucosamine and Chondroitin: Don't Be a Dummy: Become an Expert on What Glucosamine & Choneroitin Can Do by Victoria Dolby Toews, Victoria Dolby Toews; ISBN: 1591200059; http://www.amazon.com/exec/obidos/ASIN/1591200059/icongroupinterna
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Chapters on Chondroitin In order to find chapters that specifically relate to chondroitin, an excellent source of abstracts is the Combined Health Information Database. You will need to limit your search to book chapters and chondroitin using the “Detailed Search” option. Go to the following hyperlink: http://chid.nih.gov/detail/detail.html. To find book chapters, use the drop boxes at the bottom of the search page where “You may refine your search by.” Select the dates and language you prefer, and the format option “Book Chapter.” Type “chondroitin” (or synonyms) into the “For these words:” box. The following is a typical result when searching for book chapters on chondroitin: •
Oral Medications Source: in Moldwin, R.M. Interstitial Cystitis Survival Guide: Your Guide to the Latest Treatment Options and Coping Strategies. Oakland, CA: New Harbinger Publications, Inc. 2000. p. 81-112. Contact: Available from Interstitial Cystitis Association. 51 Monroe Street, Suite 1402, Rockville, MD 20850. (800) HELP-ICA or (301) 610-5300. Fax (301) 610-5308. E-mail:
[email protected]. Website: www.ichelp.org. PRICE: $12.00 plus shipping and handling. ISBN: 1572242108. Summary: More than 700,000 Americans have interstitial cystitis (IC), a condition that includes symptoms of recurring bladder pain and discomfort on urination. This chapter on oral medications used to treat IC is from a self care book designed to empower readers by simplifying the diagnostic and treatment process for IC. The primary object of the book is to build a framework for delivering proper care to the IC patient. Oral medications, used alone or in combination with other medications, will improve symptoms in most patients with IC. Patients may still have some symptoms while on oral medications, but they may be improved to the point where they wish to wait before undergoing more invasive therapy. Most of the medications used cause few significant side effects. The author notes that most of the medications discussed in this chapter have been used for many years but for other purposes. Medications and dosages may need to be changed due to side effects or poor responses. The author first discusses medications thought to coat the bladder's surface, including pentosan polysulfate sodium (Elmiron), chondroitin sulfate, and glucosamine. The author then discusses the use of antidepressants (primarily to reduce pain), including amitriptyline (Elavil); selective serotonin reuptake inhibitors (SSRIs); antihistamines, including hydroxyzine (Atarax, Vistaril); cromolyn sodium (Gastrocrom); cimetidine (Tagamet); antiseizure medications, including gabapentin (Neurontin), and carbamazepine (Tegretol); nonsteroidal antiinflammatory drugs (NSAIDs); immunosuppressants, including steroids; muscle relaxants, notably diazepam (Valium); narcotic therapy; urinary anesthetics, including phenazopyridine hydrochloride (Pyridium), atropine sulfate, benzoic acid, hyoscyamine, methenamine, methylene blue, and phenyl salicylate (Urised); anticholinergic therapy; L arginine; calcium channel blockers, including nifedipine (Procardia); and alpha blockers. The author reviews the use of each of these drugs, along with the hypothesis about why they may be of use in IC.
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Articular Cartilage Source: in Maddison, P.J.; et al., Eds. Oxford Textbook of Rheumatology. Volume 1. New York, NY: Oxford University Press, Inc. 1993. p. 233-241. Contact: Available from Oxford University Press, Inc., New York, NY.
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Summary: This chapter for health professionals focuses on the structure and function of articular cartilage. The formation of cartilage is explained. Various types of collagens are described, including fibrillar type I, II, VI, IX, X, and XI collagens. The features of aggrecan, the major proteoglycan of cartilage, are discussed. The process of proteoglycan turnover in the cartilage matrix is explained. Age-related changes in cartilage are highlighted. Cartilage response to cytokines and growth factors is examined. Models for studying the sequence of response in cartilage to trauma are presented, including the Pond-Nuki model, meniscectomy models, chemical models, and genetic models. Markers of cartilage damage in joint disease are identified, including keratan sulphate epitopes, chondroitin sulphate epitopes, proteoglycan protein epitopes, hyaluronan, collagen, and noncollagenous matrix molecules. 33 references, 2 figures, 4 tables, and 1 plate.
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CHAPTER 8. PERIODICALS AND NEWS ON CHONDROITIN Overview In this chapter, we suggest a number of news sources and present various periodicals that cover chondroitin.
News Services and Press Releases One of the simplest ways of tracking press releases on chondroitin 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 “chondroitin” (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 chondroitin. 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 “chondroitin” (or synonyms). The following was recently listed in this archive for chondroitin: •
Chondroitin supplements may lack active ingredient Source: Reuters Health eLine Date: November 12, 2003
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Topical glucosamine/chondroitin cream relieves osteoarthritis knee pain Source: Reuters Industry Breifing Date: April 08, 2003
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Glucosamine, chondroitin probably efficacious in treating osteoarthritis Source: Reuters Medical News Date: March 15, 2000
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Glucosamine, chondroitin may help arthritis Source: Reuters Health eLine Date: March 14, 2000
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Chondroitin sulfate effective in osteoarthritis patients Source: Reuters Medical News Date: January 26, 2000 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 “chondroitin” (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 “chondroitin” (or synonyms). If you know the name of a company that is relevant to chondroitin, 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/.
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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 “chondroitin” (or synonyms).
Newsletters on Chondroitin Find newsletters on chondroitin using the Combined Health Information Database (CHID). You will need to use the “Detailed Search” option. To access CHID, go to the following hyperlink: http://chid.nih.gov/detail/detail.html. Limit your search to “Newsletter” and “chondroitin.” Go to the bottom of the search page where “You may refine your search by.” Select the dates and language that you prefer. For the format option, select “Newsletter.” Type “chondroitin” (or synonyms) into the “For these words:” box. The following list was generated using the options described above: •
Glucosamine and Chondroitin for Osteoarthritis? Source: Bulletin on the Rheumatic Diseases. 50(7): 1-4. 2001. Contact: Available from Arthritis Foundation. 1330 West Peachtree Street, Atlanta, GA 30309. (800) 268-6942 or (404) 872-7100. Fax (404) 872-9559. Website: www.arthritis.org. Summary: This newsletter provides health professionals and people who have osteoarthritis (OA) with information on the therapeutic effects of glucosamine and chondroitin. The article reviews laboratory studies, placebo controlled clinical trials, comparator trials, and human disease modification studies of glucosamine and chondroitin. Evidence currently supports a modest efficacy for glucosamine and chondroitin in the treatment of OA. The products are safe and could have a role in the management of this disorder. However, further independent studies are needed to confirm findings on efficacy and to determine the clinical applicability of these compounds. In addition, preliminary findings support the idea that glucosamine and chondroitin might have disease modifying effects in OA. Research is needed to confirm these findings and to evaluate the impact of glucosamine and chondroitin on all aspects of OA progression. 1 table and 16 references.
Newsletter Articles Use the Combined Health Information Database, and limit your search criteria to “newsletter articles.” Again, you will need to use the “Detailed Search” option. Go directly to the following hyperlink: http://chid.nih.gov/detail/detail.html. Go to the bottom of the search page where “You may refine your search by.” Select the dates and language that you prefer. For the format option, select “Newsletter Article.” Type “chondroitin” (or synonyms) into the “For these words:” box. You should check back periodically with this database as it is updated every three months. The following is a typical result when searching for newsletter articles on chondroitin: •
Arthritis Cure: Does It Really Work? Source: University of California at Berkeley Wellness Letter. 13(8):1-2,5; May 1997.
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Contact: Available from Health Letter Associates, P.O. Box 412, Prince Street Station, New York, NY 10012-0007. Summary: This newsletter article for individuals with osteoarthritis critiques a book that offers advice for managing osteoarthritis (OA). Although the book provides some standard advice for managing OA, it also claims that OA suffers will experience relief from their symptoms by taking the nutritional supplements glucosamine and chondroitin sulfate. The book even proclaims that some individuals may have a complete reversal of arthritis through the rebuilding of cartilage. The article explains why this claim is inaccurate. It also offers suggestions for preventing and treating OA, including adopting a regular exercise program, maintaining a healthy weight, and using acetaminophen and nonsteroidal anti-inflammatory drugs. •
Alternative Treatments and Rheumatic Diseases Source: Bulletin on the Rheumatic Diseases. 48(7): 1-4. 1999. Contact: Available from Arthritis Foundation. 1330 West Peachtree Street, Atlanta, GA 30309. (404) 872-7100. Fax (404) 872-9559. Summary: This newsletter article provides health professionals with information on the most popular alternative treatments for arthritis, including glucosamine and chrondroitin, herbal treatments, and special diets. Each treatment is discussed in terms of the claims made, the research supporting the claims, and reasons to be cautious. Glucosamine and chondroitin are two of the most popular dietary supplements available. Treatment with these supplements is based on the hypothesis that ingesting them might increase the formative and regenerative effects on cartilage promoted by naturally occurring glucosamine and chondroitin. Studies have demonstrated that the supplements appear to relieve pain and improve function in people who have osteoarthritis (OA). In addition, they appear to be well tolerated. However, they are not regulated by the Food and Drug Administration, so there is no way to know whether the quantity of ingredients stated on the label is accurate or what other substances or impurities may be present. Herbal treatments are the most commonly used of all alternative treatments. Herbal preparations may or may not contain measurable quantities of the herb promoted on the label, and the quantity of active ingredient may vary. Herbal preparations and supplements have also been shown to contain various contaminants. Because of these problems, there are few reliable, valid clinical studies that have examined the claims about the effect of herbal medicines on various diseases. Studies have investigated the effect of Ayurvedic plant and mineral preparations, Tripterygium wilfordii, S-adenosylmethionine (SAM-e), and hydroxy-methoxy-plenyl33. Although rheumatologists have maintained that there are no special diets that alter the course of rheumatoid arthritis or OA, studies have examined the effects of omega 3 fatty acids, nightshade foods, and food allergies on arthritis. 22 references.
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Orthopedics: Remedies for Aching Knees Source: Harvard Health Letter. 26(6): 6. April 2001. Contact: Available from Harvard Health Letter. P.O. Box 380, Department BI, Boston, MA 02117. (800) 829-9045 or (617) 432-1485. E-mail:
[email protected]. Summary: This newsletter article provides people who have aching knees with information on high and low tech treatment options. One approach, viscosupplementation, involves a series of three to five injections of hyaluronic acid into the knee joint. Hyaluronic acid is a molecule found in synovial fluid that helps make it
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an effective joint lubricant. Hyalgan and Synvisc are two kinds of hyaluronic acid injections that have been approved by the Food and Drug Administration. Although cartilage replacement may become a treatment for worn out knees in the future, only tiny pieces of defective cartilage can be replaced at the present time. Microfracture is a procedure that uses a special awl to make holes in the bone beneath the cartilage. Glucosamine and chondroitin sulfate are loosely regulated dietary supplements. Orthotics are shoe inserts that can help relieve knee pain by slightly altering the angle of the joint. Strengthening the quadriceps muscle can help stabilize a bad knee and ease joint pain. Losing weight seems to be an effective preventive measure. •
Pushing the Boundaries: Alternative Therapies for Children Source: Kids Get Arthritis Too. pp. 1-3. May-June 1999. Contact: Available from Kids Get Arthritis Too (Arthritis Foundation). P.O. Box 921907, Norcross, GA 30010-1907. (800) 268-6942. Summary: This newsletter article provides the parents of children who have arthritis with information on alternative therapies. Although many physicians were once skeptical about alternative practices, with the establishment of the National Institutes of Health Office of Alternative Medicine, now known as the National Center for Complementary and Alternative Medicine, in 1992, alternative therapies are being acknowledged more openly by conventional health professionals. The article examines some of the most commonly asked about, recommended, or studied therapies for children who have arthritis, including massage therapy, biofeedback, acupuncture, and dietary supplements and modifications. Massage therapy is considered by many to be an excellent method of easing the pain and stiffness associated with arthritis. Massage therapists use a combination of strokes, friction, and pressure to help relax the muscles. Studies have demonstrated the effectiveness of massage therapy for temporary symptom relief. Biofeedback or relaxation training involves the use of electromyogram biofeedback equipment to help patients learn to monitor and reduce muscle tension. Biofeedback gives children who have arthritis a productive role in managing their own symptoms. In acupuncture, disposable stainless steel needles are used to stimulate specific points throughout the body. Studies have suggested that acupuncture may lessen pain by making the body release endorphins. There is limited evidence that certain dietary supplements, including fish and plant oils, glucosamine, and chondroitin, provide symptom relief in people who have arthritis.
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Supplements: Glucosamine for Osteoarthritis Source: Harvard Women's Health Watch. 7(9): 5. May 2000. Contact: Available from Harvard Women's Health Watch. Department SR, P.O. Box 380, Boston, MA 02117. (800) 829-5921. E-mail:
[email protected]. Summary: This newsletter article provides women who have arthritis with information on the supplement glucosamine. This popular nutritional supplement, which is derived from the shells of lobster, shrimp, and crabs, is being promoted for treating osteoarthritis (OA) naturally. Glucosamine occurs naturally in the body and encourages cartilage cells to produce glycosaminoglycans and proteoglycans. Mild and moderate OA cases have generally been treated with nonsteroidal antiinflammatory drugs, but long term use of these medications can cause serious gastrointestinal side effects. Thus, people who have OA are looking for gentler, less expensive ways to treat their pain. Numerous studies conducted in Europe and Asia suggest that glucosamine has promise as a pain reliever. The National Institutes of Health awarded the University of Utah
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School of Medicine a $6.6 million grant to coordinate the first multicenter, randomized, double blind clinical trial of glucosamine and chondroitin, a companion supplement, in patients with OA of the knee. The 1,000 patients participating in the study will take either glucosamine, chondroitin, a combination of both, or a placebo for 16 weeks and be evaluated monthly for improvement of pain. The article offers suggestions on taking glucosamine safely.
Academic Periodicals covering Chondroitin Numerous periodicals are currently indexed within the National Library of Medicine’s PubMed database that are known to publish articles relating to chondroitin. In addition to these sources, you can search for articles covering chondroitin 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
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National Institute of General Medical Sciences (NIGMS); fact sheets available at http://www.nigms.nih.gov/news/facts/
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National Library of Medicine (NLM); extensive encyclopedia (A.D.A.M., Inc.) with guidelines: http://www.nlm.nih.gov/medlineplus/healthtopics.html
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National Cancer Institute (NCI); guidelines available at http://www.cancer.gov/cancerinfo/list.aspx?viewid=5f35036e-5497-4d86-8c2c714a9f7c8d25
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National Eye Institute (NEI); guidelines available at http://www.nei.nih.gov/order/index.htm
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National Heart, Lung, and Blood Institute (NHLBI); guidelines available at http://www.nhlbi.nih.gov/guidelines/index.htm
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National Human Genome Research Institute (NHGRI); research available at http://www.genome.gov/page.cfm?pageID=10000375
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National Institute on Aging (NIA); guidelines available at http://www.nia.nih.gov/health/
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These publications are typically written by one or more of the various NIH Institutes.
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National Institute on Alcohol Abuse and Alcoholism (NIAAA); guidelines available at http://www.niaaa.nih.gov/publications/publications.htm
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National Institute of Allergy and Infectious Diseases (NIAID); guidelines available at http://www.niaid.nih.gov/publications/
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National Institute of Arthritis and Musculoskeletal and Skin Diseases (NIAMS); fact sheets and guidelines available at http://www.niams.nih.gov/hi/index.htm
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National Institute of Child Health and Human Development (NICHD); guidelines available at http://www.nichd.nih.gov/publications/pubskey.cfm
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National Institute on Deafness and Other Communication Disorders (NIDCD); fact sheets and guidelines at http://www.nidcd.nih.gov/health/
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National Institute of Dental and Craniofacial Research (NIDCR); guidelines available at http://www.nidr.nih.gov/health/
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National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK); guidelines available at http://www.niddk.nih.gov/health/health.htm
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National Institute on Drug Abuse (NIDA); guidelines available at http://www.nida.nih.gov/DrugAbuse.html
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National Institute of Environmental Health Sciences (NIEHS); environmental health information available at http://www.niehs.nih.gov/external/facts.htm
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National Institute of Mental Health (NIMH); guidelines available at http://www.nimh.nih.gov/practitioners/index.cfm
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National Institute of Neurological Disorders and Stroke (NINDS); neurological disorder information pages available at http://www.ninds.nih.gov/health_and_medical/disorder_index.htm
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National Institute of Nursing Research (NINR); publications on selected illnesses at http://www.nih.gov/ninr/news-info/publications.html
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National Institute of Biomedical Imaging and Bioengineering; general information at http://grants.nih.gov/grants/becon/becon_info.htm
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Center for Information Technology (CIT); referrals to other agencies based on keyword searches available at http://kb.nih.gov/www_query_main.asp
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National Center for Complementary and Alternative Medicine (NCCAM); health information available at http://nccam.nih.gov/health/
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National Center for Research Resources (NCRR); various information directories available at http://www.ncrr.nih.gov/publications.asp
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Office of Rare Diseases; various fact sheets available at http://rarediseases.info.nih.gov/html/resources/rep_pubs.html
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Centers for Disease Control and Prevention; various fact sheets on infectious diseases available at http://www.cdc.gov/publications.htm
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NIH Databases In addition to the various Institutes of Health that publish professional guidelines, the NIH has designed a number of databases for professionals.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
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HIV/AIDS Resources: Describes various links and databases dedicated to HIV/AIDS research: http://www.nlm.nih.gov/pubs/factsheets/aidsinfs.html
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NLM Online Exhibitions: Describes “Exhibitions in the History of Medicine”: http://www.nlm.nih.gov/exhibition/exhibition.html. Additional resources for historical scholarship in medicine: http://www.nlm.nih.gov/hmd/hmd.html
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Biotechnology Information: Access to public databases. The National Center for Biotechnology Information conducts research in computational biology, develops software tools for analyzing genome data, and disseminates biomedical information for the better understanding of molecular processes affecting human health and disease: http://www.ncbi.nlm.nih.gov/
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Population Information: The National Library of Medicine provides access to worldwide coverage of population, family planning, and related health issues, including family planning technology and programs, fertility, and population law and policy: http://www.nlm.nih.gov/databases/databases_population.html
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Cancer Information: Access to cancer-oriented databases: http://www.nlm.nih.gov/databases/databases_cancer.html
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Profiles in Science: Offering the archival collections of prominent twentieth-century biomedical scientists to the public through modern digital technology: http://www.profiles.nlm.nih.gov/
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Chemical Information: Provides links to various chemical databases and references: http://sis.nlm.nih.gov/Chem/ChemMain.html
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Clinical Alerts: Reports the release of findings from the NIH-funded clinical trials where such release could significantly affect morbidity and mortality: http://www.nlm.nih.gov/databases/alerts/clinical_alerts.html
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Space Life Sciences: Provides links and information to space-based research (including NASA): http://www.nlm.nih.gov/databases/databases_space.html
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MEDLINE: Bibliographic database covering the fields of medicine, nursing, dentistry, veterinary medicine, the healthcare system, and the pre-clinical sciences: http://www.nlm.nih.gov/databases/databases_medline.html
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Remember, for the general public, the National Library of Medicine recommends the databases referenced in MEDLINEplus (http://medlineplus.gov/ or http://www.nlm.nih.gov/medlineplus/databases.html). 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
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Visible Human Interface: Anatomically detailed, three-dimensional representations of normal male and female human bodies: http://www.nlm.nih.gov/research/visible/visible_human.html The 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 “chondroitin” 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 “chondroitin” (or synonyms) into the “For these words:” box. The following is a sample result: •
Osteoarthritis: New Insights: Part 2: Treatment Approaches Source: Annals of Internal Medicine. 133(9): 726-737. November 7, 2000. Summary: This journal article, the second of a two part summary of a National Institutes of Health conference on osteoarthritis (OA), provides health professionals with information on treatment approaches. The conference brought together experts on OA from diverse backgrounds and provided a multidisciplinary and comprehensive summary of recent advances in the prevention of OA onset, progression, and disability. The article reviews evidence for the efficacy of commonly used oral therapies, including nonopioid analgesics, nonsteroidal antiinflammatory drugs, opioid analgesics, and glucosamine and chondroitin. This is followed by a discussion of biomechanical interventions, such as exercise and bracing, and behavioral interventions, such as individualized telephone based interventions and group programs directed toward enhancing self management. The article then reports on the use of acupuncture in the treatment of OA. In addition, the article describes current surgical approaches. Four categories of nonbiological procedures are considered surgical management: osteotomy, arthroscopy, arthrodesis, and arthroplasty. The article concludes with suggestions on probable future biotechnology oriented approaches to treatment, including cartilage transplantation and tissue engineering of biologically active cells, signal molecules, and a biomatrix to assemble functional tissues and organs. 2 figures, 1 table, and 135 references. (AA-M).
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Osteoarthritis of the Knee: A Special Report Source: Physician and Sportsmedicine. Special Report. May 2000. Contact: Available from McGraw-Hill Healthcare Information. 4530 West 77th Street, Floor 3, Minneapolis, MN 55435. (800) 525-5003 or (609) 426-7070 (for subscriptions) or (952) 835-3222 (for back issues). Summary: This special report presents a series of articles that provide health professionals with information on osteoarthritis (OA) of the knee. The first article reviews the pathophysiological characteristics of OA and discusses its etiology, diagnosis, and evaluation. OA is caused by multiple factors, including genetic,
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metabolic, biochemical, enzymatic, biomechanical, and environmental factors. The history, physical examination, and radiographic examination help establish the diagnosis. The second article offers an overview of the nonoperative management of OA of the knee. Nonoperative techniques can be effective in relieving pain and improving functional ability. Nonpharmacologic treatment options include decreasing physical activity, exercising, losing weight, using supports and braces, and undergoing physiotherapy. Topical treatments include nonsteroidal anti-inflammatory drugs (NSAIDs) and capsaicin. Systemic therapies include nonnarcotic and narcotic analgesics, antidepressants, NSAIDs, chondroitin, and glucosamine. Intra-articular therapies include corticosteroids and viscosupplementation. The third article discusses operative treatment for the arthritic knee, focusing on the role of arthroscopy, the indications for joint replacement, and the new area of articular cartilage restoration and resurfacing. The choice of procedure is based on the patient's age, the extent of disease, and the desired level of physical activity. The fourth article presents case reports of active patients with arthritis who underwent viscosupplementation. The fifth article uses a question and answer format to provide health professionals with information on traditional and innovative treatments for OA of the knee. The final article is a continuing medical education activity. 5 tables and 95 references.
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 “chondroitin” (or synonyms) into the search box and click “Search.” The results will be presented in a tabular form, indicating the number of references in each database category. Results Summary Category Journal Articles Books / Periodicals / Audio Visual Consumer Health Meeting Abstracts Other Collections Total
Items Found 11100 18 814 4 0 11936
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 14
Adapted from NLM: http://gateway.nlm.nih.gov/gw/Cmd?Overview.x.
15
The NLM Gateway is currently being developed by the Lister Hill National Center for Biomedical Communications (LHNCBC) at the National Library of Medicine (NLM) of the National Institutes of Health (NIH). 16 Adapted from HSTAT: http://www.nlm.nih.gov/pubs/factsheets/hstat.html. 17
The HSTAT URL is http://hstat.nlm.nih.gov/.
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assessments from the Agency for Healthcare Research and Quality (AHRQ), as well as AHRQ’s Put Prevention Into Practice.18 Simply search by “chondroitin” (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/.
Other Commercial Databases In addition to resources maintained by official agencies, other databases exist that are commercial ventures addressing medical professionals. Here are some examples that may interest you: •
CliniWeb International: Index and table of contents to selected clinical information on the Internet; see http://www.ohsu.edu/cliniweb/.
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Medical World Search: Searches full text from thousands of selected medical sites on the Internet; see http://www.mwsearch.com/.
The Genome Project and Chondroitin In the following section, we will discuss databases and references which relate to the Genome Project and chondroitin.
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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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 “chondroitin” (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 chondroitin: •
Chondroitin Sulfate Glucuronyltransferase Web site: http://www.ncbi.nlm.nih.gov/htbin-post/Omim/dispmim?608037
•
Chondroitin Sulfate Proteoglycan 2 Web site: http://www.ncbi.nlm.nih.gov/htbin-post/Omim/dispmim?118661
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Chondroitin Sulfate Proteoglycan 3 Web site: http://www.ncbi.nlm.nih.gov/htbin-post/Omim/dispmim?600826
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Chondroitin Sulfate Proteoglycan 4 Web site: http://www.ncbi.nlm.nih.gov/htbin-post/Omim/dispmim?601172
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Chondroitin Sulfate Proteoglycan 5 Web site: http://www.ncbi.nlm.nih.gov/htbin-post/Omim/dispmim?606775
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Chondroitin Sulfate Proteoglycan 6 Web site: http://www.ncbi.nlm.nih.gov/htbin-post/Omim/dispmim?606062
•
Chondroitin-6-sulfaturia, Defective Cellular Immunity, Nephrotic Syndrome Web site: http://www.ncbi.nlm.nih.gov/htbin-post/Omim/dispmim?215250 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
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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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, 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
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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
Physician Resources
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NCBI’s Protein Sequence Information Survey Results: Web site: http://www.ncbi.nlm.nih.gov/About/proteinsurvey/
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Nucleotide Sequence Database (Genbank): Web site: http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=Nucleotide
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OMIM: Online Mendelian Inheritance in Man, Web site: http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=OMIM
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PopSet: Population study data sets, Web site: http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=Popset
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ProbeSet: Gene Expression Omnibus (GEO), Web site: http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=geo
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Protein Sequence Database: Web site: http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=Protein
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PubMed: Biomedical literature (PubMed), Web site: http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed
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Structure: Three-dimensional macromolecular structures, Web site: http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=Structure
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Taxonomy: Organisms in GenBank, Web site: http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=Taxonomy
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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 “chondroitin” (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 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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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 “chondroitin” (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).
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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 chondroitin 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 chondroitin. 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 chondroitin. 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 “chondroitin”:
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•
Other guides Arthritis http://www.nlm.nih.gov/medlineplus/arthritis.html Cartilage Disorders http://www.nlm.nih.gov/medlineplus/cartilagedisorders.html Knee Injuries and Disorders http://www.nlm.nih.gov/medlineplus/kneeinjuriesanddisorders.html Osteoarthritis http://www.nlm.nih.gov/medlineplus/osteoarthritis.html Rheumatoid Arthritis http://www.nlm.nih.gov/medlineplus/rheumatoidarthritis.html
You may also choose to use the search utility provided by MEDLINEplus at the following Web address: http://www.nlm.nih.gov/medlineplus/. Simply type a keyword into the search box and click “Search.” This utility is similar to the NIH search utility, with the exception that it only includes materials that are linked within the MEDLINEplus system (mostly patient-oriented information). It also has the disadvantage of generating unstructured results. We recommend, therefore, that you use this method only if you have a very targeted search. The Combined Health Information Database (CHID) CHID Online is a reference tool that maintains a database directory of thousands of journal articles and patient education guidelines on chondroitin. CHID offers summaries that describe the guidelines available, including contact information and pricing. CHID’s general Web site is http://chid.nih.gov/. To search this database, go to http://chid.nih.gov/detail/detail.html. In particular, you can use the advanced search options to look up pamphlets, reports, brochures, and information kits. The following was recently posted in this archive: •
Questions & Answers: NIH Glucosamine/Chondroitin Arthritis Intervention Trial (GAIT) Source: Gaithersburg, MD: National Center for Complementary and Alternative Medicine. 2002. 5 p. Contact: Available from National Center for Complementary and Alternative Medicine Clearinghouse. P.O. Box 7923, Gaithersburg, MD 20898. (888) 644-6226; INTERNATIONAL PHONE: (301) 519-3153; TTY: (866) 464-3615; FAX: (866) 464-3616; EMAIL:
[email protected]. PRICE: Free. Publication Number: D147. Summary: This National Institutes of Health fact sheet provides information about the Glucosamine/Chondroitin Arthritis Intervention Trial in a question and answer format. It discusses the overall purpose of the trial as well as the circumstances that prompted the NIH to study glucosamine and chondroitin for osteoarthritis. It describes the basic design of the study and includes information about the number of patients included, who is eligible to take part, and how people can sign up to participate in the study. The fact sheet provides general facts about osteoarthritis and the dietary supplements glucosamine and chondroitin, which are being tested to treat the condition.
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Glucosamine and Chondroitin Sulfate Source: Atlanta, GA: Arthritis Foundation. 1999. 8 p. Contact: Available from Arthritis Foundation. P.O. Box 1616, Alpharetta, GA 300091616. (800) 207-8633. Fax (credit card orders only) (770) 442-9742. Website: www.arthritis.org. PRICE: Single copy free from local Arthritis Foundation chapter (call (800) 283-7800 for closest local chapter); bulk orders may be purchased from address above. Summary: This pamphlet uses a question and answer format to provide people who have arthritis with information on glucosamine and chondroitin sulfate. These substances, which are found naturally in the body, are sold as dietary or nutritional supplements. They have been used in Europe to treat osteoarthritis since the 1980s. Studies conducted primarily in Europe have shown that some people with mild to moderate osteoarthritis who took either substance experienced pain relief at a level similar to that of nonsteroidal anti-inflammatory drugs. Glucosamine and chondroitin are unregulated, so the quality and content may vary widely. A person choosing to take these supplements should consult his or her physician to make sure that osteoarthritis is the cause of pain and should choose products sold by large, well established companies. Recommended dosages are 1,500 milligrams (mg) per day for glucosamine and 1,200 mg per day for chondroitin. Common side effects are increased intestinal gas and softened stools. There are some people who need to be especially careful when considering the use of these supplements.
Healthfinder™ Healthfinder™ is sponsored by the U.S. Department of Health and Human Services and offers links to hundreds of other sites that contain healthcare information. This Web site is located at http://www.healthfinder.gov. Again, keyword searches can be used to find guidelines. The following was recently found in this database: •
Glucosamine and Chondroitin Sulfate Summary: Facts about the dietary (nutritional) supplements glucosamine and chondroitin sulfate and their use as treatment options for arthritis. Source: Arthritis Foundation http://www.healthfinder.gov/scripts/recordpass.asp?RecordType=0&RecordID=6007 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 chondroitin. 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.
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Additional Web Sources A number of Web sites are available to the public that often link to government sites. These can also point you in the direction of essential information. The following is a representative sample: •
AOL: http://search.aol.com/cat.adp?id=168&layer=&from=subcats
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Family Village: http://www.familyvillage.wisc.edu/specific.htm
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Google: http://directory.google.com/Top/Health/Conditions_and_Diseases/
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Med Help International: http://www.medhelp.org/HealthTopics/A.html
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Open Directory Project: http://dmoz.org/Health/Conditions_and_Diseases/
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Yahoo.com: http://dir.yahoo.com/Health/Diseases_and_Conditions/
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WebMDHealth: http://my.webmd.com/health_topics
Finding Associations There are several Internet directories that provide lists of medical associations with information on or resources relating to chondroitin. By consulting all of associations listed in this chapter, you will have nearly exhausted all sources for patient associations concerned with chondroitin. 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 chondroitin. 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 “chondroitin” (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
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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 “chondroitin”. 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 “chondroitin” (or synonyms) into the “For these words:” box. You should check back periodically with this database since it is updated every three months. The National Organization for Rare Disorders, Inc. The National Organization for Rare Disorders, Inc. has prepared a Web site that provides, at no charge, lists of associations organized by health topic. You can access this database at the following Web site: http://www.rarediseases.org/search/orgsearch.html. Type “chondroitin” (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/
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Alabama: Richard M. Scrushy Library (American Sports Medicine Institute)
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Arizona: Samaritan Regional Medical Center: The Learning Center (Samaritan Health System, Phoenix, Arizona), http://www.samaritan.edu/library/bannerlibs.htm
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California: Kris Kelly Health Information Center (St. Joseph Health System, Humboldt), http://www.humboldt1.com/~kkhic/index.html
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California: Community Health Library of Los Gatos, http://www.healthlib.org/orgresources.html
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California: Consumer Health Program and Services (CHIPS) (County of Los Angeles Public Library, Los Angeles County Harbor-UCLA Medical Center Library) - Carson, CA, http://www.colapublib.org/services/chips.html
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California: Gateway Health Library (Sutter Gould Medical Foundation)
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California: Health Library (Stanford University Medical Center), http://wwwmed.stanford.edu/healthlibrary/
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California: Patient Education Resource Center - Health Information and Resources (University of California, San Francisco), http://sfghdean.ucsf.edu/barnett/PERC/default.asp
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California: Redwood Health Library (Petaluma Health Care District), http://www.phcd.org/rdwdlib.html
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California: Los Gatos PlaneTree Health Library, http://planetreesanjose.org/
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California: Sutter Resource Library (Sutter Hospitals Foundation, Sacramento), http://suttermedicalcenter.org/library/
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California: Health Sciences Libraries (University of California, Davis), http://www.lib.ucdavis.edu/healthsci/
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California: ValleyCare Health Library & Ryan Comer Cancer Resource Center (ValleyCare Health System, Pleasanton), http://gaelnet.stmarysca.edu/other.libs/gbal/east/vchl.html
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California: Washington Community Health Resource Library (Fremont), http://www.healthlibrary.org/
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Colorado: William V. Gervasini Memorial Library (Exempla Healthcare), http://www.saintjosephdenver.org/yourhealth/libraries/
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Connecticut: Hartford Hospital Health Science Libraries (Hartford Hospital), http://www.harthosp.org/library/
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Connecticut: Healthnet: Connecticut Consumer Health Information Center (University of Connecticut Health Center, Lyman Maynard Stowe Library), http://library.uchc.edu/departm/hnet/
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
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Delaware: Consumer Health Library (Christiana Care Health System, Eugene du Pont Preventive Medicine & Rehabilitation Institute, Wilmington), http://www.christianacare.org/health_guide/health_guide_pmri_health_info.cfm
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Delaware: Lewis B. Flinn Library (Delaware Academy of Medicine, Wilmington), http://www.delamed.org/chls.html
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Georgia: Family Resource Library (Medical College of Georgia, Augusta), http://cmc.mcg.edu/kids_families/fam_resources/fam_res_lib/frl.htm
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Georgia: Health Resource Center (Medical Center of Central Georgia, Macon), http://www.mccg.org/hrc/hrchome.asp
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Hawaii: Hawaii Medical Library: Consumer Health Information Service (Hawaii Medical Library, Honolulu), http://hml.org/CHIS/
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Idaho: DeArmond Consumer Health Library (Kootenai Medical Center, Coeur d’Alene), http://www.nicon.org/DeArmond/index.htm
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Illinois: Health Learning Center of Northwestern Memorial Hospital (Chicago), http://www.nmh.org/health_info/hlc.html
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Illinois: Medical Library (OSF Saint Francis Medical Center, Peoria), http://www.osfsaintfrancis.org/general/library/
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Kentucky: Medical Library - Services for Patients, Families, Students & the Public (Central Baptist Hospital, Lexington), http://www.centralbap.com/education/community/library.cfm
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Kentucky: University of Kentucky - Health Information Library (Chandler Medical Center, Lexington), http://www.mc.uky.edu/PatientEd/
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Louisiana: Alton Ochsner Medical Foundation Library (Alton Ochsner Medical Foundation, New Orleans), http://www.ochsner.org/library/
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Louisiana: Louisiana State University Health Sciences Center Medical LibraryShreveport, http://lib-sh.lsuhsc.edu/
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Maine: Franklin Memorial Hospital Medical Library (Franklin Memorial Hospital, Farmington), http://www.fchn.org/fmh/lib.htm
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Maine: Gerrish-True Health Sciences Library (Central Maine Medical Center, Lewiston), http://www.cmmc.org/library/library.html
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Maine: Hadley Parrot Health Science Library (Eastern Maine Healthcare, Bangor), http://www.emh.org/hll/hpl/guide.htm
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Maine: Maine Medical Center Library (Maine Medical Center, Portland), http://www.mmc.org/library/
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Maine: Parkview Hospital (Brunswick), http://www.parkviewhospital.org/
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Maine: Southern Maine Medical Center Health Sciences Library (Southern Maine Medical Center, Biddeford), http://www.smmc.org/services/service.php3?choice=10
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Maine: Stephens Memorial Hospital’s Health Information Library (Western Maine Health, Norway), http://www.wmhcc.org/Library/
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Manitoba, Canada: Consumer & Patient Health Information Service (University of Manitoba Libraries), http://www.umanitoba.ca/libraries/units/health/reference/chis.html
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Manitoba, Canada: J.W. Crane Memorial Library (Deer Lodge Centre, Winnipeg), http://www.deerlodge.mb.ca/crane_library/about.asp
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Maryland: Health Information Center at the Wheaton Regional Library (Montgomery County, Dept. of Public Libraries, Wheaton Regional Library), http://www.mont.lib.md.us/healthinfo/hic.asp
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Massachusetts: Baystate Medical Center Library (Baystate Health System), http://www.baystatehealth.com/1024/
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Massachusetts: Boston University Medical Center Alumni Medical Library (Boston University Medical Center), http://med-libwww.bu.edu/library/lib.html
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Massachusetts: Lowell General Hospital Health Sciences Library (Lowell General Hospital, Lowell), http://www.lowellgeneral.org/library/HomePageLinks/WWW.htm
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Massachusetts: Paul E. Woodard Health Sciences Library (New England Baptist Hospital, Boston), http://www.nebh.org/health_lib.asp
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Massachusetts: St. Luke’s Hospital Health Sciences Library (St. Luke’s Hospital, Southcoast Health System, New Bedford), http://www.southcoast.org/library/
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Massachusetts: Treadwell Library Consumer Health Reference Center (Massachusetts General Hospital), http://www.mgh.harvard.edu/library/chrcindex.html
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Massachusetts: UMass HealthNet (University of Massachusetts Medical School, Worchester), http://healthnet.umassmed.edu/
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Michigan: Botsford General Hospital Library - Consumer Health (Botsford General Hospital, Library & Internet Services), http://www.botsfordlibrary.org/consumer.htm
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Michigan: Helen DeRoy Medical Library (Providence Hospital and Medical Centers), http://www.providence-hospital.org/library/
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Michigan: Marquette General Hospital - Consumer Health Library (Marquette General Hospital, Health Information Center), http://www.mgh.org/center.html
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Michigan: Patient Education Resouce Center - University of Michigan Cancer Center (University of Michigan Comprehensive Cancer Center, Ann Arbor), http://www.cancer.med.umich.edu/learn/leares.htm
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Michigan: Sladen Library & Center for Health Information Resources - Consumer Health Information (Detroit), http://www.henryford.com/body.cfm?id=39330
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Montana: Center for Health Information (St. Patrick Hospital and Health Sciences Center, Missoula)
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National: Consumer Health Library Directory (Medical Library Association, Consumer and Patient Health Information Section), http://caphis.mlanet.org/directory/index.html
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National: National Network of Libraries of Medicine (National Library of Medicine) provides library services for health professionals in the United States who do not have access to a medical library, http://nnlm.gov/
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National: NN/LM List of Libraries Serving the Public (National Network of Libraries of Medicine), http://nnlm.gov/members/
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Nevada: Health Science Library, West Charleston Library (Las Vegas-Clark County Library District, Las Vegas), http://www.lvccld.org/special_collections/medical/index.htm
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New Hampshire: Dartmouth Biomedical Libraries (Dartmouth College Library, Hanover), http://www.dartmouth.edu/~biomed/resources.htmld/conshealth.htmld/
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New Jersey: Consumer Health Library (Rahway Hospital, Rahway), http://www.rahwayhospital.com/library.htm
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New Jersey: Dr. Walter Phillips Health Sciences Library (Englewood Hospital and Medical Center, Englewood), http://www.englewoodhospital.com/links/index.htm
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New Jersey: Meland Foundation (Englewood Hospital and Medical Center, Englewood), http://www.geocities.com/ResearchTriangle/9360/
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New York: Choices in Health Information (New York Public Library) - NLM Consumer Pilot Project participant, http://www.nypl.org/branch/health/links.html
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New York: Health Information Center (Upstate Medical University, State University of New York, Syracuse), http://www.upstate.edu/library/hic/
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New York: Health Sciences Library (Long Island Jewish Medical Center, New Hyde Park), http://www.lij.edu/library/library.html
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New York: ViaHealth Medical Library (Rochester General Hospital), http://www.nyam.org/library/
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Ohio: Consumer Health Library (Akron General Medical Center, Medical & Consumer Health Library), http://www.akrongeneral.org/hwlibrary.htm
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Oklahoma: The Health Information Center at Saint Francis Hospital (Saint Francis Health System, Tulsa), http://www.sfh-tulsa.com/services/healthinfo.asp
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Oregon: Planetree Health Resource Center (Mid-Columbia Medical Center, The Dalles), http://www.mcmc.net/phrc/
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Pennsylvania: Community Health Information Library (Milton S. Hershey Medical Center, Hershey), http://www.hmc.psu.edu/commhealth/
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Pennsylvania: Community Health Resource Library (Geisinger Medical Center, Danville), http://www.geisinger.edu/education/commlib.shtml
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Pennsylvania: HealthInfo Library (Moses Taylor Hospital, Scranton), http://www.mth.org/healthwellness.html
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Pennsylvania: Hopwood Library (University of Pittsburgh, Health Sciences Library System, Pittsburgh), http://www.hsls.pitt.edu/guides/chi/hopwood/index_html
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Pennsylvania: Koop Community Health Information Center (College of Physicians of Philadelphia), http://www.collphyphil.org/kooppg1.shtml
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Pennsylvania: Learning Resources Center - Medical Library (Susquehanna Health System, Williamsport), http://www.shscares.org/services/lrc/index.asp
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Pennsylvania: Medical Library (UPMC Health System, Pittsburgh), http://www.upmc.edu/passavant/library.htm
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Quebec, Canada: Medical Library (Montreal General Hospital), http://www.mghlib.mcgill.ca/
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South Dakota: Rapid City Regional Hospital Medical Library (Rapid City Regional Hospital), http://www.rcrh.org/Services/Library/Default.asp
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Texas: Houston HealthWays (Houston Academy of Medicine-Texas Medical Center Library), http://hhw.library.tmc.edu/
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Washington: Community Health Library (Kittitas Valley Community Hospital), http://www.kvch.com/
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Washington: Southwest Washington Medical Center Library (Southwest Washington Medical Center, Vancouver), http://www.swmedicalcenter.com/body.cfm?id=72
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ONLINE GLOSSARIES The Internet provides access to a number of free-to-use medical dictionaries. The National Library of Medicine has compiled the following list of online dictionaries: •
ADAM Medical Encyclopedia (A.D.A.M., Inc.), comprehensive medical reference: http://www.nlm.nih.gov/medlineplus/encyclopedia.html
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MedicineNet.com Medical Dictionary (MedicineNet, Inc.): http://www.medterms.com/Script/Main/hp.asp
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Merriam-Webster Medical Dictionary (Inteli-Health, Inc.): http://www.intelihealth.com/IH/
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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/
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Rare Diseases Terms (Office of Rare Diseases): http://ord.aspensys.com/asp/diseases/diseases.asp
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Technology Glossary (National Library of Medicine) - Health Care Technology: http://www.nlm.nih.gov/nichsr/ta101/ta10108.htm
Beyond these, MEDLINEplus contains a very patient-friendly encyclopedia covering every aspect of medicine (licensed from A.D.A.M., Inc.). The ADAM Medical Encyclopedia can be accessed at http://www.nlm.nih.gov/medlineplus/encyclopedia.html. ADAM is also available on commercial Web sites such as drkoop.com (http://www.drkoop.com/) and Web MD (http://my.webmd.com/adam/asset/adam_disease_articles/a_to_z/a).
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
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Patient Education: Glossaries (DMOZ Open Directory Project): http://dmoz.org/Health/Education/Patient_Education/Glossaries/
•
Web of Online Dictionaries (Bucknell University): http://www.yourdictionary.com/diction5.html#medicine
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CHONDROITIN DICTIONARY The definitions below are derived from official public sources, including the National Institutes of Health [NIH] and the European Union [EU]. Abdomen: That portion of the body that lies between the thorax and the pelvis. [NIH] Abdominal: Having to do with the abdomen, which is the part of the body between the chest and the hips that contains the pancreas, stomach, intestines, liver, gallbladder, and other organs. [NIH] Abdominal Pain: Sensation of discomfort, distress, or agony in the abdominal region. [NIH] Aberrant: Wandering or deviating from the usual or normal course. [EU] Abrasion: 1. The wearing away of a substance or structure (such as the skin or the teeth) through some unusual or abnormal mechanical process. 2. An area of body surface denuded of skin or mucous membrane by some unusual or abnormal mechanical process. [EU] Acceptor: A substance which, while normally not oxidized by oxygen or reduced by hydrogen, can be oxidized or reduced in presence of a substance which is itself undergoing oxidation or reduction. [NIH] Acetaminophen: Analgesic antipyretic derivative of acetanilide. It has weak antiinflammatory properties and is used as a common analgesic, but may cause liver, blood cell, and kidney damage. [NIH] Acetylcholine: A neurotransmitter. Acetylcholine in vertebrates is the major transmitter at neuromuscular junctions, autonomic ganglia, parasympathetic effector junctions, a subset of sympathetic effector junctions, and at many sites in the central nervous system. It is generally not used as an administered drug because it is broken down very rapidly by cholinesterases, but it is useful in some ophthalmological applications. [NIH] Acetylgalactosamine: The N-acetyl derivative of galactosamine. [NIH] Acetylglucosamine: The N-acetyl derivative of glucosamine. [NIH] Acne: A disorder of the skin marked by inflammation of oil glands and hair glands. [NIH] Actin: Essential component of the cell skeleton. [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] Adenine: A purine base and a fundamental unit of adenine nucleotides. [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 Diphosphate: Adenosine 5'-(trihydrogen diphosphate). An adenine nucleotide containing two phosphate groups esterified to the sugar moiety at the 5'-position. [NIH]
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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] Adhesions: Pathological processes consisting of the union of the opposing surfaces of a wound. [NIH] Adjustment: The dynamic process wherein the thoughts, feelings, behavior, and biophysiological mechanisms of the individual continually change to adjust to the environment. [NIH] Adjuvant: A substance which aids another, such as an auxiliary remedy; in immunology, nonspecific stimulator (e.g., BCG vaccine) of the immune response. [EU] Adrenal Medulla: The inner part of the adrenal gland; it synthesizes, stores and releases catecholamines. [NIH] Adrenergic: Activated by, characteristic of, or secreting epinephrine or substances with similar activity; the term is applied to those nerve fibres that liberate norepinephrine at a synapse when a nerve impulse passes, i.e., the sympathetic fibres. [EU] Adsorption: The condensation of gases, liquids, or dissolved substances on the surfaces of solids. It includes adsorptive phenomena of bacteria and viruses as well as of tissues treated with exogenous drugs and chemicals. [NIH] Adverse Effect: An unwanted side effect of treatment. [NIH] Aerosol: A solution of a drug which can be atomized into a fine mist for inhalation therapy. [EU]
Afferent: Concerned with the transmission of neural impulse toward the central part of the nervous system. [NIH] 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] Agar: A complex sulfated polymer of galactose units, extracted from Gelidium cartilagineum, Gracilaria confervoides, and related red algae. It is used as a gel in the preparation of solid culture media for microorganisms, as a bulk laxative, in making emulsions, and as a supporting medium for immunodiffusion and immunoelectrophoresis. [NIH]
Agarose: A polysaccharide complex, free of nitrogen and prepared from agar-agar which is produced by certain seaweeds (red algae). It dissolves in warm water to form a viscid solution. [NIH] Age of Onset: The age or period of life at which a disease or the initial symptoms or
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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] Agrin: A protein component of the synaptic basal lamina. It has been shown to induce clustering of acetylcholine receptors on the surface of muscle fibers and other synaptic molecules in both synapse regeneration and development. [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] Alertness: A state of readiness to detect and respond to certain specified small changes occurring at random intervals in the environment. [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] Alkaline Phosphatase: An enzyme that catalyzes the conversion of an orthophosphoric monoester and water to an alcohol and orthophosphate. EC 3.1.3.1. [NIH] Alkaloid: A member of a large group of chemicals that are made by plants and have nitrogen in them. Some alkaloids have been shown to work against cancer. [NIH] Alleles: Mutually exclusive forms of the same gene, occupying the same locus on homologous chromosomes, and governing the same biochemical and developmental process. [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] 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
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herbal preparations; the drinking of special teas; and practices such as massage therapy, magnet therapy, spiritual healing, and meditation. [NIH] Alveolar Process: The thickest and spongiest part of the maxilla and mandible hollowed out into deep cavities for the teeth. [NIH] Amblyopia: A nonspecific term referring to impaired vision. Major subcategories include stimulus deprivation-induced amblyopia and toxic amblyopia. Stimulus deprivationinduced amblopia is a developmental disorder of the visual cortex. A discrepancy between visual information received by the visual cortex from each eye results in abnormal cortical development. Strabismus and refractive errors may cause this condition. Toxic amblyopia is a disorder of the optic nerve which is associated with alcoholism, tobacco smoking, and other toxins and as an adverse effect of the use of some medications. [NIH] Ameliorated: 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 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] Amino-terminal: The end of a protein or polypeptide chain that contains a free amino group (-NH2). [NIH] Amitriptyline: Tricyclic antidepressant with anticholinergic and sedative properties. It appears to prevent the re-uptake of norepinephrine and serotonin at nerve terminals, thus potentiating the action of these neurotransmitters. Amitriptyline also appears to antaganize cholinergic and alpha-1 adrenergic responses to bioactive amines. [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] Ammonium Sulfate: Sulfuric acid diammonium salt. It is used in fractionation of proteins. [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] Anabolic: Relating to, characterized by, or promoting anabolism. [EU] Anaerobic: 1. Lacking molecular oxygen. 2. Growing, living, or occurring in the absence of molecular oxygen; pertaining to an anaerobe. [EU] Anaesthesia: Loss of feeling or sensation. Although the term is used for loss of tactile sensibility, or of any of the other senses, it is applied especially to loss of the sensation of
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pain, as it is induced to permit performance of surgery or other painful procedures. [EU] Analgesic: An agent that alleviates pain without causing loss of consciousness. [EU] Analogous: Resembling or similar in some respects, as in function or appearance, but not in origin or development;. [EU] Anaphylatoxins: The family of peptides C3a, C4a, C5a, and C5a des-arginine produced in the serum during complement activation. They produce smooth muscle contraction, mast cell histamine release, affect platelet aggregation, and act as mediators of the local inflammatory process. The order of anaphylatoxin activity from strongest to weakest is C5a, C3a, C4a, and C5a des-arginine. The latter is the so-called "classical" anaphylatoxin but shows no spasmogenic activity though it contains some chemotactic ability. [NIH] Anatomical: Pertaining to anatomy, or to the structure of the organism. [EU] Androgens: A class of sex hormones associated with the development and maintenance of the secondary male sex characteristics, sperm induction, and sexual differentiation. In addition to increasing virility and libido, they also increase nitrogen and water retention and stimulate skeletal growth. [NIH] Anecdotal report: An incomplete description of the medical and treatment history of one or more patients. Anecdotal reports may be published in places other than peer-reviewed, scientific journals. [NIH] Anemia: A reduction in the number of circulating erythrocytes or in the quantity of hemoglobin. [NIH] Anesthesia: A state characterized by loss of feeling or sensation. This depression of nerve function is usually the result of pharmacologic action and is induced to allow performance of surgery or other painful procedures. [NIH] Anesthetics: Agents that are capable of inducing a total or partial loss of sensation, especially tactile sensation and pain. They may act to induce general anesthesia, in which an unconscious state is achieved, or may act locally to induce numbness or lack of sensation at a targeted site. [NIH] Aneuploidy: The chromosomal constitution of cells which deviate from the normal by the addition or subtraction of chromosomes or chromosome pairs. In a normally diploid cell the loss of a chromosome pair is termed nullisomy (symbol: 2N-2), the loss of a single chromosome is monosomy (symbol: 2N-1), the addition of a chromosome pair is tetrasomy (symbol: 2N+2), the addition of a single chromosome is trisomy (symbol: 2N+1). [NIH] Anginal: Pertaining to or characteristic of angina. [EU] Angiogenesis: Blood vessel formation. Tumor angiogenesis is the growth of blood vessels from surrounding tissue to a solid tumor. This is caused by the release of chemicals by the tumor. [NIH] Angioplasty: Endovascular reconstruction of an artery, which may include the removal of atheromatous plaque and/or the endothelial lining as well as simple dilatation. These are procedures performed by catheterization. When reconstruction of an artery is performed surgically, it is called endarterectomy. [NIH] Angiotensinogen: An alpha-globulin of which a fragment of 14 amino acids is converted by renin to angiotensin I, the inactive precursor of angiotensin II. It is a member of the serpin superfamily. [NIH] Animal model: An animal with a disease either the same as or like a disease in humans. Animal models are used to study the development and progression of diseases and to test new treatments before they are given to humans. Animals with transplanted human cancers or other tissues are called xenograft models. [NIH]
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Anionic: Pertaining to or containing an anion. [EU] Anions: Negatively charged atoms, radicals or groups of atoms which travel to the anode or positive pole during electrolysis. [NIH] Ankle: That part of the lower limb directly above the foot. [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] 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] Anticholinergic: An agent that blocks the parasympathetic nerves. Called also parasympatholytic. [EU] Anticoagulant: A drug that helps prevent blood clots from forming. Also called a blood thinner. [NIH] Anticonvulsant: An agent that prevents or relieves convulsions. [EU] Antidepressant: A drug used to treat depression. [NIH] 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] Anti-infective: An agent that so acts. [EU] Anti-Infective Agents: Substances that prevent infectious agents or organisms from spreading or kill infectious agents in order to prevent the spread of infection. [NIH] Anti-inflammatory: Having to do with reducing inflammation. [NIH] Anti-Inflammatory Agents: Substances that reduce or suppress inflammation. [NIH] Antimicrobial: Killing microorganisms, or suppressing their multiplication or growth. [EU]
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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] Antipruritic: Relieving or preventing itching. [EU] Antipsychotic: Effective in the treatment of psychosis. Antipsychotic drugs (called also neuroleptic drugs and major tranquilizers) are a chemically diverse (including phenothiazines, thioxanthenes, butyrophenones, dibenzoxazepines, dibenzodiazepines, and diphenylbutylpiperidines) but pharmacologically similar class of drugs used to treat schizophrenic, paranoid, schizoaffective, and other psychotic disorders; acute delirium and dementia, and manic episodes (during induction of lithium therapy); to control the movement disorders associated with Huntington's chorea, Gilles de la Tourette's syndrome, and ballismus; and to treat intractable hiccups and severe nausea and vomiting. Antipsychotic agents bind to dopamine, histamine, muscarinic cholinergic, a-adrenergic, and serotonin receptors. Blockade of dopaminergic transmission in various areas is thought to be responsible for their major effects : antipsychotic action by blockade in the mesolimbic 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] Antithrombotic: Preventing or interfering with the formation of thrombi; an agent that so acts. [EU] Antitussive: An agent that relieves or prevents cough. [EU] Antiviral: Destroying viruses or suppressing their replication. [EU] Anxiety: Persistent feeling of dread, apprehension, and impending disaster. [NIH] Aorta: The main trunk of the systemic arteries. [NIH] Aortic Valve: The valve between the left ventricle and the ascending aorta which prevents backflow into the left ventricle. [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] Aponeurosis: Tendinous expansion consisting of a fibrous or membranous sheath which serves as a fascia to enclose or bind a group of muscles. [NIH] Apoptosis: One of the two mechanisms by which cell death occurs (the other being the pathological process of necrosis). Apoptosis is the mechanism responsible for the physiological deletion of cells and appears to be intrinsically programmed. It is characterized by distinctive morphologic changes in the nucleus and cytoplasm, chromatin cleavage at regularly spaced sites, and the endonucleolytic cleavage of genomic DNA (DNA fragmentation) at internucleosomal sites. This mode of cell death serves as a balance to mitosis in regulating the size of animal tissues and in mediating pathologic processes associated with tumor growth. [NIH] Applicability: A list of the commodities to which the candidate method can be applied as presented or with minor modifications. [NIH]
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Aqueous: Having to do with water. [NIH] Arachidonate 12-Lipoxygenase: An enzyme that catalyzes the oxidation of arachidonic acid to yield 12-hydroperoxyarachidonate (12-HPETE) which is itself rapidly converted by a peroxidase to 12-hydroxy-5,8,10,14-eicosatetraenoate (12-HETE). The 12-hydroperoxides are preferentially formed in platelets. EC 1.13.11.31. [NIH] Arachidonate 15-Lipoxygenase: An enzyme that catalyzes the oxidation of arachidonic acid to yield 15-hydroperoxyarachidonate (15-HPETE) which is rapidly converted to 15-hydroxy5,8,11,13-eicosatetraenoate (15-HETE). The 15-hydroperoxides are preferentially formed in neutrophils and lymphocytes. EC 1.13.11.33. [NIH] Arachidonate Lipoxygenases: Enzymes catalyzing the oxidation of arachidonic acid to hydroperoxyarachidonates (HPETES). These products are then rapidly converted by a peroxidase to hydroxyeicosatetraenoic acids (HETES). The positional specificity of the enzyme reaction varies from tissue to tissue. The final lipoxygenase pathway leads to the leukotrienes. EC 1.13.11.- . [NIH] 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] 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] Arthralgia: Pain in the joint. [NIH] Arthroplasty: Surgical reconstruction of a joint to relieve pain or restore motion. [NIH] Arthroscopy: Endoscopic examination, therapy and surgery of the joint. [NIH] Articular: Of or pertaining to a joint. [EU] Ascorbic Acid: A six carbon compound related to glucose. It is found naturally in citrus fruits and many vegetables. Ascorbic acid is an essential nutrient in human diets, and necessary to maintain connective tissue and bone. Its biologically active form, vitamin C, functions as a reducing agent and coenzyme in several metabolic pathways. Vitamin C is considered an antioxidant. [NIH] Aseptic: Free from infection or septic material; sterile. [EU] Aspartate: A synthetic amino acid. [NIH]
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Aspirin: A drug that reduces pain, fever, inflammation, and blood clotting. Aspirin belongs to the family of drugs called nonsteroidal anti-inflammatory agents. It is also being studied in cancer prevention. [NIH] Assay: Determination of the amount of a particular constituent of a mixture, or of the biological or pharmacological potency of a drug. [EU] Asthenopia: Term generally used to describe complaints related to refractive error, ocular muscle imbalance, including pain or aching around the eyes, burning and itchiness of the eyelids, ocular fatigue, and headaches. [NIH] Astigmatism: A condition in which the surface of the cornea is not spherical; causes a blurred image to be received at the retina. [NIH] Astrocytes: The largest and most numerous neuroglial cells in the brain and spinal cord. Astrocytes (from "star" cells) are irregularly shaped with many long processes, including those with "end feet" which form the glial (limiting) membrane and directly and indirectly contribute to the blood brain barrier. They regulate the extracellular ionic and chemical environment, and "reactive astrocytes" (along with microglia) respond to injury. Astrocytes have high- affinity transmitter uptake systems, voltage-dependent and transmitter-gated ion channels, and can release transmitter, but their role in signaling (as in many other functions) is not well understood. [NIH] 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] Atherogenic: Causing the formation of plaque in the lining of the arteries. [NIH] Atrial: Pertaining to an atrium. [EU] Atrioventricular: Pertaining to an atrium of the heart and to a ventricle. [EU] Atrium: A chamber; used in anatomical nomenclature to designate a chamber affording entrance to another structure or organ. Usually used alone to designate an atrium of the heart. [EU] Atrophy: Decrease in the size of a cell, tissue, organ, or multiple organs, associated with a variety of pathological conditions such as abnormal cellular changes, ischemia, malnutrition, or hormonal changes. [NIH] Atropine: A toxic alkaloid, originally from Atropa belladonna, but found in other plants, mainly Solanaceae. [NIH] Auditory: Pertaining to the sense of hearing. [EU] Autoimmune disease: A condition in which the body recognizes its own tissues as foreign and directs an immune response against them. [NIH] Autonomic: Self-controlling; functionally independent. [EU] Autonomic Nervous System: The enteric, parasympathetic, and sympathetic nervous systems taken together. Generally speaking, the autonomic nervous system regulates the internal environment during both peaceful activity and physical or emotional stress. Autonomic activity is controlled and integrated by the central nervous system, especially the hypothalamus and the solitary nucleus, which receive information relayed from visceral afferents; these and related central and sensory structures are sometimes (but not here) considered to be part of the autonomic nervous system itself. [NIH]
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Autopsy: Postmortem examination of the body. [NIH] Autoradiography: A process in which radioactive material within an object produces an image when it is in close proximity to a radiation sensitive emulsion. [NIH] Avian: A plasmodial infection in birds. [NIH] Axonal: Condition associated with metabolic derangement of the entire neuron and is manifest by degeneration of the distal portion of the nerve fiber. [NIH] Axons: Nerve fibers that are capable of rapidly conducting impulses away from the neuron cell body. [NIH] Axotomy: Transection or severing of an axon. This type of denervation is used often in experimental studies on neuronal physiology and neuronal death or survival, toward an understanding of nervous system disease. [NIH] Bacteria: Unicellular prokaryotic microorganisms which generally possess rigid cell walls, multiply by cell division, and exhibit three principal forms: round or coccal, rodlike or bacillary, and spiral or spirochetal. [NIH] Bacterial Infections: Infections by bacteria, general or unspecified. [NIH] 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] 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 cell carcinoma: A type of skin cancer that arises from the basal cells, small round cells found in the lower part (or base) of the epidermis, the outer layer of the skin. [NIH] Basal cells: Small, round cells found in the lower part (or base) of the epidermis, the outer layer of the skin. [NIH] Basal Ganglia: Large subcortical nuclear masses derived from the telencephalon and located in the basal regions of the cerebral hemispheres. [NIH] Basal Ganglia Diseases: Diseases of the basal ganglia including the putamen; globus pallidus; claustrum; amygdala; and caudate nucleus. Dyskinesias (most notably involuntary movements and alterations of the rate of movement) represent the primary clinical manifestations of these disorders. Common etiologies include cerebrovascular disease; neurodegenerative diseases; and craniocerebral trauma. [NIH] Base: In chemistry, the nonacid part of a salt; a substance that combines with acids to form salts; a substance that dissociates to give hydroxide ions in aqueous solutions; a substance whose molecule or ion can combine with a proton (hydrogen ion); a substance capable of donating a pair of electrons (to an acid) for the formation of a coordinate covalent bond. [EU] Basement Membrane: Ubiquitous supportive tissue adjacent to epithelium and around smooth and striated muscle cells. This tissue contains intrinsic macromolecular components such as collagen, laminin, and sulfated proteoglycans. As seen by light microscopy one of its subdivisions is the basal (basement) lamina. [NIH] Basophils: Granular leukocytes characterized by a relatively pale-staining, lobate nucleus and cytoplasm containing coarse dark-staining granules of variable size and stainable by basic dyes. [NIH] Behavioral Sciences: Disciplines concerned with the study of human and animal behavior.
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[NIH]
Belladonna: A species of very poisonous Solanaceous plants yielding atropine (hyoscyamine), scopolamine, and other belladonna alkaloids, used to block the muscarinic autonomic nervous system. [NIH] Benign: Not cancerous; does not invade nearby tissue or spread to other parts of the body. [NIH]
Benzocaine: A surface anesthetic that acts by preventing transmission of impulses along nerve fibers and at nerve endings. [NIH] Benzoic Acid: A fungistatic compound that is widely used as a food preservative. It is conjugated to glycine in the liver and excreted as hippuric acid. [NIH] Benzyl Alcohol: A colorless liquid with a sharp burning taste and slight odor. It is used as a local anesthetic and to reduce pain associated with lidocaine injection. Also, it is used in the manufacture of other benzyl compounds, as a pharmaceutic aid, and in perfumery and flavoring. [NIH] Beta-pleated: Particular three-dimensional pattern of amyloidoses. [NIH] Beta-sheet: Two or more parallel or anti-parallel strands are arranged in rows. [NIH] Beta-Thromboglobulin: A platelet-specific protein which is released when platelets aggregate. Elevated plasma levels have been reported after deep venous thrombosis, preeclampsia, myocardial infarction with mural thrombosis, and myeloproliferative disorders. Measurement of beta-thromboglobulin in biological fluids by radioimmunoassay is used for the diagnosis and assessment of progress of thromboembolic disorders. [NIH] 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 Ducts: Tubes that carry bile from the liver to the gallbladder for storage and to the small intestine for use in digestion. [NIH] Biliary: Having to do with the liver, bile ducts, and/or gallbladder. [NIH] Biliary Tract: The gallbladder and its ducts. [NIH] Bilirubin: A bile pigment that is a degradation product of heme. [NIH] Binding agent: A substance that makes a loose mixture stick together. For example, binding agents can be used to make solid pills from loose powders. [NIH] Binding Sites: The reactive parts of a macromolecule that directly participate in its specific combination with another molecule. [NIH] Bioassays: Determination of the relative effective strength of a substance (as a vitamin, hormone, or drug) by comparing its effect on a test organism with that of a standard preparation. [NIH] Bioavailability: The degree to which a drug or other substance becomes available to the target tissue after administration. [EU] Bioavailable: The ability of a drug or other substance to be absorbed and used by the body. Orally bioavailable means that a drug or other substance that is taken by mouth can be
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absorbed and used by the body. [NIH] Biochemical: Relating to biochemistry; characterized by, produced by, or involving chemical reactions in living organisms. [EU] Biochemical Phenomena: Biochemical functions, activities, and processes at organic and molecular levels in humans, animals, microorganisms, and plants. [NIH] Biodegradation: The series of processes by which living organisms degrade pollutant chemicals, organic wastes, pesticides, and implantable materials. [NIH] Biological Phenomena: Biological functions and activities at the organic and molecular levels in humans, animals, microorganisms, and plants. For biochemical and metabolic processes, biochemical phenomena is available. [NIH] Biological response modifier: BRM. A substance that stimulates the body's response to infection and disease. [NIH] Biological therapy: Treatment to stimulate or restore the ability of the immune system to fight infection and disease. Also used to lessen side effects that may be caused by some cancer treatments. Also known as immunotherapy, biotherapy, or biological response modifier (BRM) therapy. [NIH] Biological Transport: The movement of materials (including biochemical substances and drugs) across cell membranes and epithelial layers, usually by passive diffusion. [NIH] Biomarkers: Substances sometimes found in an increased amount in the blood, other body fluids, or tissues and that may suggest the presence of some types of cancer. Biomarkers include CA 125 (ovarian cancer), CA 15-3 (breast cancer), CEA (ovarian, lung, breast, pancreas, and GI tract cancers), and PSA (prostate cancer). Also called tumor markers. [NIH] Biomechanics: The study of the application of mechanical laws and the action of forces to living structures. [NIH] Biophysics: The science of physical phenomena and processes in living organisms. [NIH] Biopsy: Removal and pathologic examination of specimens in the form of small pieces of tissue from the living body. [NIH] Biosynthesis: The building up of a chemical compound in the physiologic processes of a living organism. [EU] Biotechnology: Body of knowledge related to the use of organisms, cells or cell-derived constituents for the purpose of developing products which are technically, scientifically and clinically useful. Alteration of biologic function at the molecular level (i.e., genetic engineering) is a central focus; laboratory methods used include transfection and cloning technologies, sequence and structure analysis algorithms, computer databases, and gene and protein structure function analysis and prediction. [NIH] Biotin: Hexahydro-2-oxo-1H-thieno(3,4-d)imidazole-4-pentanoic acid. Growth factor present in minute amounts in every living cell. It occurs mainly bound to proteins or polypeptides and is abundant in liver, kidney, pancreas, yeast, and milk.The biotin content of cancerous tissue is higher than that of normal tissue. [NIH] Biotransformation: The chemical alteration of an exogenous substance by or in a biological system. The alteration may inactivate the compound or it may result in the production of an active metabolite of an inactive parent compound. The alteration may be either nonsynthetic (oxidation-reduction, hydrolysis) or synthetic (glucuronide formation, sulfate conjugation, acetylation, methylation). This also includes metabolic detoxication and clearance. [NIH] Bladder: The organ that stores urine. [NIH]
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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] Blood Coagulation: The process of the interaction of blood coagulation factors that results in an insoluble fibrin clot. [NIH] Blood Coagulation Factors: Endogenous substances, usually proteins, that are involved in the blood coagulation process. [NIH] Blood Glucose: Glucose in blood. [NIH] Blood Platelets: Non-nucleated disk-shaped cells formed in the megakaryocyte and found in the blood of all mammals. They are mainly involved in blood coagulation. [NIH] Blood pressure: The pressure of blood against the walls of a blood vessel or heart chamber. Unless there is reference to another location, such as the pulmonary artery or one of the heart chambers, it refers to the pressure in the systemic arteries, as measured, for example, in the forearm. [NIH] Blood vessel: A tube in the body through which blood circulates. Blood vessels include a network of arteries, arterioles, capillaries, venules, and veins. [NIH] Blot: To transfer DNA, RNA, or proteins to an immobilizing matrix such as nitrocellulose. [NIH]
Body Fluids: Liquid components of living organisms. [NIH] Bone Marrow: The soft tissue filling the cavities of bones. Bone marrow exists in two types, yellow and red. Yellow marrow is found in the large cavities of large bones and consists mostly of fat cells and a few primitive blood cells. Red marrow is a hematopoietic tissue and is the site of production of erythrocytes and granular leukocytes. Bone marrow is made up of a framework of connective tissue containing branching fibers with the frame being filled with marrow cells. [NIH] Bone Resorption: Bone loss due to osteoclastic activity. [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] Bowel Movement: Body wastes passed through the rectum and anus. [NIH] Brachytherapy: A collective term for interstitial, intracavity, and surface radiotherapy. It uses small sealed or partly-sealed sources that may be placed on or near the body surface or within a natural body cavity or implanted directly into the tissues. [NIH] Bradykinin: A nonapeptide messenger that is enzymatically produced from kallidin in the blood where it is a potent but short-lived agent of arteriolar dilation and increased capillary permeability. Bradykinin is also released from mast cells during asthma attacks, from gut walls as a gastrointestinal vasodilator, from damaged tissues as a pain signal, and may be a neurotransmitter. [NIH] Brain 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),
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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] 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] 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] Buccal: Pertaining to or directed toward the cheek. In dental anatomy, used to refer to the buccal surface of a tooth. [EU] Bupivacaine: A widely used local anesthetic agent. [NIH] Burns: Injuries to tissues caused by contact with heat, steam, chemicals (burns, chemical), electricity (burns, electric), or the like. [NIH] Burns, Electric: Burns produced by contact with electric current or from a sudden discharge of electricity. [NIH] Bursitis: Inflammation of a bursa, occasionally accompanied by a calcific deposit in the underlying supraspinatus tendon; the most common site is the subdeltoid bursa. [EU] Bypass: A surgical procedure in which the doctor creates a new pathway for the flow of body fluids. [NIH] Cadherins: A group of functionally related glycoproteins responsible for the calciumdependent cell-to-cell adhesion mechanism. They are divided into subclasses E-, P-, and Ncadherins, which are distinct in immunological specificity and tissue distribution. They promote cell adhesion via a homophilic mechanism. These compounds play a role in the construction of tissues and of the whole animal body. [NIH] Caffeine: A methylxanthine naturally occurring in some beverages and also used as a pharmacological agent. Caffeine's most notable pharmacological effect is as a central nervous system stimulant, increasing alertness and producing agitation. It also relaxes smooth muscle, stimulates cardiac muscle, stimulates diuresis, and appears to be useful in the treatment of some types of headache. Several cellular actions of caffeine have been observed, but it is not entirely clear how each contributes to its pharmacological profile. Among the most important are inhibition of cyclic nucleotide phosphodiesterases, antagonism of adenosine receptors, and modulation of intracellular calcium handling. [NIH] 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] Calcineurin: A calcium- and calmodulin-binding protein present in highest concentrations in the central nervous system. Calcineurin is composed of two subunits. A catalytic subunit, calcineurin A, and a regulatory subunit, calcineurin B, with molecular weights of about 60 kD and 19 kD, respectively. Calcineurin has been shown to dephosphorylate a number of phosphoproteins including histones, myosin light chain, and the regulatory subunit of
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cAMP-dependent protein kinase. It is involved in the regulation of signal transduction and is the target of an important class of immunophilin-immunosuppressive drug complexes in T-lymphocytes that act by inhibiting T-cell activation. EC 3.1.3.-. [NIH] Calcium: A basic element found in nearly all organized tissues. It is a member of the alkaline earth family of metals with the atomic symbol Ca, atomic number 20, and atomic weight 40. Calcium is the most abundant mineral in the body and combines with phosphorus to form calcium phosphate in the bones and teeth. It is essential for the normal functioning of nerves and muscles and plays a role in blood coagulation (as factor IV) and in many enzymatic processes. [NIH] Calcium channel blocker: A drug used to relax the blood vessel and heart muscle, causing pressure inside blood vessels to drop. It also can regulate heart rhythm. [NIH] Calcium Channel Blockers: A class of drugs that act by selective inhibition of calcium influx through cell membranes or on the release and binding of calcium in intracellular pools. Since they are inducers of vascular and other smooth muscle relaxation, they are used in the drug therapy of hypertension and cerebrovascular spasms, as myocardial protective agents, and in the relaxation of uterine spasms. [NIH] Calcium Compounds: Inorganic compounds that contain calcium as an integral part of the molecule. [NIH] Calcium Hydroxide: Ca(OH)2. A white powder that has many therapeutic uses. Because of its ability to stimulate mineralization, it is found in many dental formulations. [NIH] Calculi: An abnormal concretion occurring mostly in the urinary and biliary tracts, usually composed of mineral salts. Also called stones. [NIH] Callus: A callosity or hard, thick skin; the bone-like reparative substance that is formed round the edges and fragments of broken bone. [NIH] 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] Camphor: A bicyclic monoterpene ketone found widely in plant (primarily the camphor tree, Cinnamomum camphora). Natural camphor is used topically as a skin antipruritic and as an anti-infective agent. [NIH] Cannula: A tube for insertion into a duct or cavity; during insertion its lumen is usually occupied by a trocar. [EU] Capillary: Any one of the minute vessels that connect the arterioles and venules, forming a network in nearly all parts of the body. Their walls act as semipermeable membranes for the interchange of various substances, including fluids, between the blood and tissue fluid; called also vas capillare. [EU] Capillary Fragility: The lack of resistance, or susceptibility, of capillaries to damage or disruption under conditions of increased stress. [NIH] 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] Capsaicin: Cytotoxic alkaloid from various species of Capsicum (pepper, paprika), of the Solanaceae. [NIH] Capsular: Cataract which is initiated by an opacification at the surface of the lens. [NIH]
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Capsules: Hard or soft soluble containers used for the oral administration of medicine. [NIH] Carbamazepine: An anticonvulsant used to control grand mal and psychomotor or focal seizures. Its mode of action is not fully understood, but some of its actions resemble those of phenytoin; although there is little chemical resemblance between the two compounds, their three-dimensional structure is similar. [NIH] 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] Carbohydrate Sequence: The sequence of carbohydrates within polysaccharides, glycoproteins, and glycolipids. [NIH] Carbon Dioxide: A colorless, odorless gas that can be formed by the body and is necessary for the respiration cycle of plants and animals. [NIH] Carboxy: Cannabinoid. [NIH] Carcinogenic: Producing carcinoma. [EU] Carcinogens: Substances that increase the risk of neoplasms in humans or animals. Both genotoxic chemicals, which affect DNA directly, and nongenotoxic chemicals, which induce neoplasms by other mechanism, are included. [NIH] 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] Cardiopulmonary: Having to do with the heart and lungs. [NIH] Cardiopulmonary Bypass: Diversion of the flow of blood from the entrance of the right atrium directly to the aorta (or femoral artery) via an oxygenator thus bypassing both the heart and lungs. [NIH] Cardiovascular: Having to do with the heart and blood vessels. [NIH] Cardiovascular disease: Any abnormal condition characterized by dysfunction of the heart and blood vessels. CVD includes atherosclerosis (especially coronary heart disease, which can lead to heart attacks), cerebrovascular disease (e.g., stroke), and hypertension (high blood pressure). [NIH] Carotene: The general name for a group of pigments found in green, yellow, and leafy vegetables, and yellow fruits. The pigments are fat-soluble, unsaturated aliphatic hydrocarbons functioning as provitamins and are converted to vitamin A through enzymatic processes in the intestinal wall. [NIH] Carotenoids: Substance found in yellow and orange fruits and vegetables and in dark green, leafy vegetables. May reduce the risk of developing cancer. [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
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treatment. [NIH] Caspase: Enzyme released by the cell at a crucial stage in apoptosis in order to shred all cellular proteins. [NIH] Castor Oil: Oil obtained from seeds of Ricinus communis that is used as a cathartic and as a plasticizer. [NIH] Catabolism: Any destructive metabolic process by which organisms convert substances into excreted compounds. [EU] Cataract: An opacity, partial or complete, of one or both eyes, on or in the lens or capsule, especially an opacity impairing vision or causing blindness. The many kinds of cataract are classified by their morphology (size, shape, location) or etiology (cause and time of occurrence). [EU] Catechin: Extracted from Uncaria gambier, Acacia catechu and other plants; it stabilizes collagen and is therefore used in tanning and dyeing; it prevents capillary fragility and abnormal permeability, but was formerly used as an antidiarrheal. [NIH] Catecholamine: A group of chemical substances manufactured by the adrenal medulla and secreted during physiological stress. [NIH] Cathepsins: A group of lysosomal proteinases or endopeptidases found in aqueous extracts of a variety of animal tissue. They function optimally within an acidic pH range. [NIH] 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] Catheters: A small, flexible tube that may be inserted into various parts of the body to inject or remove liquids. [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] Cell: The individual unit that makes up all of the tissues of the body. All living things are made up of one or more cells. [NIH] Cell Adhesion: Adherence of cells to surfaces or to other cells. [NIH] Cell Adhesion Molecules: Surface ligands, usually glycoproteins, that mediate cell-to-cell adhesion. Their functions include the assembly and interconnection of various vertebrate systems, as well as maintenance of tissue integration, wound healing, morphogenic movements, cellular migrations, and metastasis. [NIH] Cell 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]
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Cell Division: The fission of a cell. [NIH] Cell membrane: Cell membrane = plasma membrane. The structure enveloping a cell, enclosing the cytoplasm, and forming a selective permeability barrier; it consists of lipids, proteins, and some carbohydrates, the lipids thought to form a bilayer in which integral proteins are embedded to varying degrees. [EU] Cell motility: The ability of a cell to move. [NIH] Cell Movement: The movement of cells from one location to another. [NIH] Cell proliferation: An increase in the number of cells as a result of cell growth and cell division. [NIH] Cell Survival: The span of viability of a cell characterized by the capacity to perform certain functions such as metabolism, growth, reproduction, some form of responsiveness, and adaptability. [NIH] Cell Transplantation: Transference of cells within an individual, between individuals of the same species, or between individuals of different species. [NIH] Cellobiose: A disaccharide consisting of two glucose units in beta (1-4) glycosidic linkage. Obtained from the partial hydrolysis of cellulose. [NIH] Cellular Structures: Components of a cell. [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] Cerebellar: Pertaining to the cerebellum. [EU] 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] Cerebrovascular: Pertaining to the blood vessels of the cerebrum, or brain. [EU] Cerebrum: The largest part of the brain. It is divided into two hemispheres, or halves, called the cerebral hemispheres. The cerebrum controls muscle functions of the body and also controls speech, emotions, reading, writing, and learning. [NIH] Cervix: The lower, narrow end of the uterus that forms a canal between the uterus and vagina. [NIH] Cetirizine: A potent second-generation histamine H1 antagonist that is effective in the treatment of allergic rhinitis, chronic urticaria, and pollen-induced asthma. Unlike many traditional antihistamines, it does not cause drowsiness or anticholinergic side effects. [NIH] Chaperonins: A class of sequence-related molecular chaperones found in bacteria, mitochondria, and plastids. Chaperonins are abundant constitutive proteins that increase in amount after stresses such as heat shock, bacterial infection of macrophages, and an increase in the cellular content of unfolded proteins. Bacterial chaperonins are major immunogens in human bacterial infections because of their accumulation during the stress of infection. Two members of this class of chaperones are chaperonin 10 and chaperonin 60. [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]
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Chelation: Combination with a metal in complexes in which the metal is part of a ring. [EU] Chemokines: Class of pro-inflammatory cytokines that have the ability to attract and activate leukocytes. They can be divided into at least three structural branches: C (chemokines, C), CC (chemokines, CC), and CXC (chemokines, CXC), according to variations in a shared cysteine motif. [NIH] Chemotactic Factors: Chemical substances that attract or repel cells or organisms. The concept denotes especially those factors released as a result of tissue injury, invasion, or immunologic activity, that attract leukocytes, macrophages, or other cells to the site of infection or insult. [NIH] Chemotaxis: The movement of cells or organisms toward or away from a substance in response to its concentration gradient. [NIH] Chemotherapy: Treatment with anticancer drugs. [NIH] Chimeras: Organism that contains a mixture of genetically different cells. [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] Cholinergic: Resembling acetylcholine in pharmacological action; stimulated by or releasing acetylcholine or a related compound. [EU] Chondrogenesis: The formation of cartilage. This process is directed by chondrocytes which continually divide and lay down matrix during development. It is sometimes a precursor to osteogenesis. [NIH] Chondroitin Lyases: Enzymes which catalyze the elimination of delta-4,5-D-glucuronate residues from polysaccharides containing 1,4-beta-hexosaminyl and 1,3-beta-D-glucuronosyl or 1,3-alpha-L-iduronosyl linkages thereby bringing about depolymerization. EC 4.2.2.4 acts on chondroitin sulfate A and C as well as on dermatan sulfate and slowly on hyaluronate. EC 4.2.2.5 acts on chondroitin sulfate A and C. [NIH] Chondroitin sulfate: The major glycosaminoglycan (a type of sugar molecule) in cartilage. [NIH]
Choroid: The thin, highly vascular membrane covering most of the posterior of the eye between the retina and sclera. [NIH] Chromatin: The material of chromosomes. It is a complex of DNA, histones, and nonhistone proteins (chromosomal proteins, non-histone) found within the nucleus of a cell. [NIH] Chromosomal: Pertaining to chromosomes. [EU] Chromosome: Part of a cell that contains genetic information. Except for sperm and eggs, all human cells contain 46 chromosomes. [NIH] Chronic: A disease or condition that persists or progresses over a long period of time. [NIH] Chronic 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]
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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 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] Cimetidine: A histamine congener, it competitively inhibits histamine binding to H2 receptors. Cimetidine has a range of pharmacological actions. It inhibits gastric acid secretion, as well as pepsin and gastrin output. It also blocks the activity of cytochrome P450. [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 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] 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] Clot Retraction: Retraction of a clot resulting from contraction of platelet pseudopods attached to fibrin strands that is dependent on the contractile protein thrombosthenin. Used as a measure of platelet function. [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
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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] 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] 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] Collagen: A polypeptide substance comprising about one third of the total protein in mammalian organisms. It is the main constituent of skin, connective tissue, and the organic substance of bones and teeth. Different forms of collagen are produced in the body but all consist of three alpha-polypeptide chains arranged in a triple helix. Collagen is differentiated from other fibrous proteins, such as elastin, by the content of proline, hydroxyproline, and hydroxylysine; by the absence of tryptophan; and particularly by the high content of polar groups which are responsible for its swelling properties. [NIH] Collagen disease: A term previously used to describe chronic diseases of the connective tissue (e.g., rheumatoid arthritis, systemic lupus erythematosus, and systemic sclerosis), but now is thought to be more appropriate for diseases associated with defects in collagen, which is a component of the connective tissue. [NIH] Collagenases: Enzymes that catalyze the degradation of collagen by acting on the peptide bonds. EC 3.4.24.-. [NIH] Collapse: 1. A state of extreme prostration and depression, with failure of circulation. 2. Abnormal falling in of the walls of any part of organ. [EU] Colloidal: Of the nature of a colloid. [EU] Combination Therapy: Association of 3 drugs to treat AIDS (AZT + DDC or DDI + protease inhibitor). [NIH] Common Bile Duct: The largest biliary duct. It is formed by the junction of the cystic duct and the hepatic duct. [NIH] Communis: Common tendon of the rectus group of muscles that surrounds the optic foramen and a portion of the superior orbital fissure, to the anterior margin of which it is attached at the spina recti lateralis. [NIH] Complement: A term originally used to refer to the heat-labile factor in serum that causes immune cytolysis, the lysis of antibody-coated cells, and now referring to the entire functionally related system comprising at least 20 distinct serum proteins that is the effector not only of immune cytolysis but also of other biologic functions. Complement activation occurs by two different sequences, the classic and alternative pathways. The proteins of the classic pathway are termed 'components of complement' and are designated by the symbols C1 through C9. C1 is a calcium-dependent complex of three distinct proteins C1q, C1r and C1s. The proteins of the alternative pathway (collectively referred to as the properdin system) and complement regulatory proteins are known by semisystematic or trivial names. Fragments resulting from proteolytic cleavage of complement proteins are designated with lower-case letter suffixes, e.g., C3a. Inactivated fragments may be designated with the suffix 'i', e.g. C3bi. Activated components or complexes with biological activity are designated by a bar over the symbol e.g. C1 or C4b,2a. The classic pathway is activated by the binding of C1 to classic pathway activators, primarily antigen-antibody complexes containing IgM, IgG1,
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IgG3; C1q binds to a single IgM molecule or two adjacent IgG molecules. The alternative pathway can be activated by IgA immune complexes and also by nonimmunologic materials including bacterial endotoxins, microbial polysaccharides, and cell walls. Activation of the classic pathway triggers an enzymatic cascade involving C1, C4, C2 and C3; activation of the alternative pathway triggers a cascade involving C3 and factors B, D and P. Both result in the cleavage of C5 and the formation of the membrane attack complex. Complement activation also results in the formation of many biologically active complement fragments that act as anaphylatoxins, opsonins, or chemotactic factors. [EU] Complement Activation: The sequential activation of serum components C1 through C9, initiated by an erythrocyte-antibody complex or by microbial polysaccharides and properdin, and producing an inflammatory response. [NIH] Complementary and alternative medicine: CAM. Forms of treatment that are used in addition to (complementary) or instead of (alternative) standard treatments. These practices are not considered standard medical approaches. CAM includes dietary supplements, megadose vitamins, herbal preparations, special teas, massage therapy, magnet therapy, spiritual healing, and meditation. [NIH] Complementary medicine: Practices not generally recognized by the medical community as standard or conventional medical approaches and used to enhance or complement the standard treatments. Complementary medicine includes the taking of dietary supplements, megadose vitamins, and herbal preparations; the drinking of special teas; and practices such as massage therapy, magnet therapy, spiritual healing, and meditation. [NIH] Computational Biology: A field of biology concerned with the development of techniques for the collection and manipulation of biological data, and the use of such data to make biological discoveries or predictions. This field encompasses all computational methods and theories applicable to molecular biology and areas of computer-based techniques for solving biological problems including manipulation of models and datasets. [NIH] Concentric: Having a common center of curvature or symmetry. [NIH] 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] Cone: One of the special retinal receptor elements which are presumed to be primarily concerned with perception of light and color stimuli when the eye is adapted to light. [NIH] Conjugated: Acting or operating as if joined; simultaneous. [EU] Conjugation: 1. The act of joining together or the state of being conjugated. 2. A sexual process seen in bacteria, ciliate protozoa, and certain fungi in which nuclear material is exchanged during the temporary fusion of two cells (conjugants). In bacterial genetics a form of sexual reproduction in which a donor bacterium (male) contributes some, or all, of its DNA (in the form of a replicated set) to a recipient (female) which then incorporates differing genetic information into its own chromosome by recombination and passes the recombined set on to its progeny by replication. In ciliate protozoa, two conjugants of separate mating types exchange micronuclear material and then separate, each now being a fertilized cell. In certain fungi, the process involves fusion of two gametes, resulting in union of their nuclei and formation of a zygote. 3. In chemistry, the joining together of two compounds to produce another compound, such as the combination of a toxic product with some substance in the body to form a detoxified product, which is then eliminated. [EU] Conjunctiva: The mucous membrane that lines the inner surface of the eyelids and the anterior part of the sclera. [NIH] Connective Tissue: Tissue that supports and binds other tissues. It consists of connective
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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] Connective Tissue Diseases: A heterogeneous group of disorders, some hereditary, others acquired, characterized by abnormal structure or function of one or more of the elements of connective tissue, i.e., collagen, elastin, or the mucopolysaccharides. [NIH] Connexins: A group of homologous proteins which form the intermembrane channels of gap junctions. The connexins are the products of an identified gene family which has both highly conserved and highly divergent regions. The variety contributes to the wide range of functional properties of gap junctions. [NIH] Consciousness: Sense of awareness of self and of the environment. [NIH] Constipation: Infrequent or difficult evacuation of feces. [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] Contact Inhibition: Arrest of cell locomotion or cell division when two cells come into contact. [NIH] Contraception: Use of agents, devices, methods, or procedures which diminish the likelihood of or prevent conception. [NIH] Contraceptive: An agent that diminishes the likelihood of or prevents conception. [EU] Contracture: A condition of fixed high resistance to passive stretch of a muscle, resulting from fibrosis of the tissues supporting the muscles or the joints, or from disorders of the muscle fibres. [EU] Contraindications: Any factor or sign that it is unwise to pursue a certain kind of action or treatment, e. g. giving a general anesthetic to a person with pneumonia. [NIH] Control group: In a clinical trial, the group that does not receive the new treatment being studied. This group is compared to the group that receives the new treatment, to see if the new treatment works. [NIH] Controlled clinical trial: A clinical study that includes a comparison (control) group. The comparison group receives a placebo, another treatment, or no treatment at all. [NIH] Controlled study: An experiment or clinical trial that includes a comparison (control) group. [NIH]
Coordination: Muscular or motor regulation or the harmonious cooperation of muscles or groups of muscles, in a complex action or series of actions. [NIH] Cor: The muscular organ that maintains the circulation of the blood. c. adiposum a heart that has undergone fatty degeneration or that has an accumulation of fat around it; called also fat or fatty, heart. c. arteriosum the left side of the heart, so called because it contains oxygenated (arterial) blood. c. biloculare a congenital anomaly characterized by failure of formation of the atrial and ventricular septums, the heart having only two chambers, a single atrium and a single ventricle, and a common atrioventricular valve. c. bovinum (L. 'ox heart') a greatly enlarged heart due to a hypertrophied left ventricle; called also c. taurinum and bucardia. c. dextrum (L. 'right heart') the right atrium and ventricle. c. hirsutum, c. villosum. c. mobile (obs.) an abnormally movable heart. c. pendulum a heart so movable that it seems to be hanging by the great blood vessels. c. pseudotriloculare biatriatum a
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congenital cardiac anomaly in which the heart functions as a three-chambered heart because of tricuspid atresia, the right ventricle being extremely small or rudimentary and the right atrium greatly dilated. Blood passes from the right to the left atrium and thence disease due to pulmonary hypertension secondary to disease of the lung, or its blood vessels, with hypertrophy of the right ventricle. [EU] Cornea: The transparent part of the eye that covers the iris and the pupil and allows light to enter the inside. [NIH] Corneal Stroma: The lamellated connective tissue constituting the thickest layer of the cornea between the Bowman and Descemet membranes. [NIH] Corneal Transplantation: Partial or total replacement of the cornea from one human or animal to another. [NIH] Corneal Ulcer: Loss of epithelial tissue from the surface of the cornea due to progressive erosion and necrosis of the tissue; usually caused by bacterial, fungal, or viral infection. [NIH] Corneum: The superficial layer of the epidermis containing keratinized cells. [NIH] Coronary: Encircling in the manner of a crown; a term applied to vessels; nerves, ligaments, etc. The term usually denotes the arteries that supply the heart muscle and, by extension, a pathologic involvement of them. [EU] Coronary heart disease: A type of heart disease caused by narrowing of the coronary 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] Corpuscle: A small mass or body; a sensory nerve end bulb; a cell, especially that of the blood or the lymph. [NIH] Cortex: The outer layer of an organ or other body structure, as distinguished from the internal substance. [EU] Cortical: Pertaining to or of the nature of a cortex or bark. [EU] 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] Cranial: Pertaining to the cranium, or to the anterior (in animals) or superior (in humans) end of the body. [EU] Creatine: An amino acid that occurs in vertebrate tissues and in urine. In muscle tissue, creatine generally occurs as phosphocreatine. Creatine is excreted as creatinine in the urine. [NIH]
Creatinine: A compound that is excreted from the body in urine. Creatinine levels are measured to monitor kidney function. [NIH] Cribriform: Pierced with small holes as in a sieve. Refers to the appearance of a tumor when viewed under a microscope. The tumor appears to have open spaces or small holes inside. [NIH]
Cromolyn Sodium: A chromone complex that acts by inhibiting the release of chemical mediators from sensitized mast cells. It is used in the prophylactic treatment of both allergic and exercise-induced asthma, but does not affect an established asthmatic attack. [NIH] Crossing-over: The exchange of corresponding segments between chromatids of
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homologous chromosomes during meiosia, forming a chiasma. [NIH] Cryofixation: Fixation of a tissue by localized cooling at very low temperature. [NIH] Cryopreservation: Preservation of cells, tissues, organs, or embryos by freezing. In histological preparations, cryopreservation or cryofixation is used to maintain the existing form, structure, and chemical composition of all the constituent elements of the specimens. [NIH]
Cues: Signals for an action; that specific portion of a perceptual field or pattern of stimuli to which a subject has learned to respond. [NIH] Cultured cells: Animal or human cells that are grown in the laboratory. [NIH] Curare: Plant extracts from several species, including Strychnos toxifera, S. castelnaei, S. crevauxii, and Chondodendron tomentosum, that produce paralysis of skeletal muscle and are used adjunctively with general anesthesia. These extracts are toxic and must be used with the administration of artificial respiration. [NIH] Curative: Tending to overcome disease and promote recovery. [EU] Cutaneous: Having to do with the skin. [NIH] Cyanide: An extremely toxic class of compounds that can be lethal on inhaling of ingesting in minute quantities. [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] Cysteine: A thiol-containing non-essential amino acid that is oxidized to form cystine. [NIH] Cystic Duct: The tube that carries bile from the gallbladder into the common bile duct and the small intestine. [NIH] Cystine: A covalently linked dimeric nonessential amino acid formed by the oxidation of cysteine. Two molecules of cysteine are joined together by a disulfide bridge to form cystine. [NIH]
Cystitis: Inflammation of the urinary bladder. [EU] Cytochrome: Any electron transfer hemoprotein having a mode of action in which the transfer of a single electron is effected by a reversible valence change of the central iron atom of the heme prosthetic group between the +2 and +3 oxidation states; classified as cytochromes a in which the heme contains a formyl side chain, cytochromes b, which contain protoheme or a closely similar heme that is not covalently bound to the protein, cytochromes c in which protoheme or other heme is covalently bound to the protein, and cytochromes d in which the iron-tetrapyrrole has fewer conjugated double bonds than the hemes have. Well-known cytochromes have been numbered consecutively within groups and are designated by subscripts (beginning with no subscript), e.g. cytochromes c, c1, C2, . New cytochromes are named according to the wavelength in nanometres of the absorption maximum of the a-band of the iron (II) form in pyridine, e.g., c-555. [EU] Cytokine: Small but highly potent protein that modulates the activity of many cell types, including T and B cells. [NIH] Cytoplasm: The protoplasm of a cell exclusive of that of the nucleus; it consists of a continuous aqueous solution (cytosol) and the organelles and inclusions suspended in it (phaneroplasm), and is the site of most of the chemical activities of the cell. [EU] Cytoskeletal Proteins: Major constituent of the cytoskeleton found in the cytoplasm of eukaryotic cells. They form a flexible framework for the cell, provide attachment points for organelles and formed bodies, and make communication between parts of the cell possible. [NIH]
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Cytoskeleton: The network of filaments, tubules, and interconnecting filamentous bridges which give shape, structure, and organization to the cytoplasm. [NIH] Cytotoxic: Cell-killing. [NIH] Cytotoxicity: Quality of being capable of producing a specific toxic action upon cells of special organs. [NIH] Databases, Bibliographic: Extensive collections, reputedly complete, of references and citations to books, articles, publications, etc., generally on a single subject or specialized subject area. Databases can operate through automated files, libraries, or computer disks. The concept should be differentiated from factual databases which is used for collections of data and facts apart from bibliographic references to them. [NIH] Daunorubicin: Very toxic anthracycline aminoglycoside antibiotic isolated from Streptomyces peucetius and others, used in treatment of leukemias and other neoplasms. [NIH]
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] Decubitus: An act of lying down; also the position assumed in lying down. [EU] Decubitus Ulcer: An ulceration caused by prolonged pressure in patients permitted to lie too still for a long period of time. The bony prominences of the body are the most frequently affected sites. The ulcer is caused by ischemia of the underlying structures of the skin, fat, and muscles as a result of the sustained and constant pressure. [NIH] Defense Mechanisms: Unconscious process used by an individual or a group of individuals in order to cope with impulses, feelings or ideas which are not acceptable at their conscious level; various types include reaction formation, projection and self reversal. [NIH] Degenerative: Undergoing degeneration : tending to degenerate; having the character of or involving degeneration; causing or tending to cause degeneration. [EU] Deletion: A genetic rearrangement through loss of segments of DNA (chromosomes), bringing sequences, which are normally separated, into close proximity. [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] Density: The logarithm to the base 10 of the opacity of an exposed and processed film. [NIH] Dental implant: A small metal pin placed inside the jawbone to mimic the root of a tooth. Dental implants can be used to help anchor a false tooth or teeth, or a crown or bridge. [NIH] Dentate Gyrus: Gray matter situated above the gyrus hippocampi. It is composed of three layers. The molecular layer is continuous with the hippocampus in the hippocampal fissure. The granular layer consists of closely arranged spherical or oval neurons, called granule cells, whose axons pass through the polymorphic layer ending on the dendrites of pyramidal cells in the hippocampus. [NIH] 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
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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] 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] Detergents: Purifying or cleansing agents, usually salts of long-chain aliphatic bases or acids, that exert cleansing (oil-dissolving) and antimicrobial effects through a surface action that depends on possessing both hydrophilic and hydrophobic properties. [NIH] Deuterium: Deuterium. The stable isotope of hydrogen. It has one neutron and one proton in the nucleus. [NIH] Developed Countries: Countries that have reached a level of economic achievement through an increase of production, per capita income and consumption, and utilization of natural and human resources. [NIH] Dextran Sulfate: Long-chain polymer of glucose containing 17-20% sulfur. It has been used as an anticoagulant and also has been shown to inhibit the binding of HIV-1 to CD4+ Tlymphocytes. It is commonly used as both an experimental and clinical laboratory reagent and has been investigated for use as an antiviral agent, in the treatment of hypolipidemia, and for the prevention of free radical damage, among other applications. [NIH] Diabetes Mellitus: A heterogeneous group of disorders that share glucose intolerance in common. [NIH] Diagnostic procedure: A method used to identify a disease. [NIH] Dialysis Solutions: Solutions prepared for exchange across a semipermeable membrane of solutes below a molecular size determined by the cutoff threshold of the membrane material. [NIH] Diamines: Organic chemicals which have two amino groups in an aliphatic chain. [NIH] Diaphragm: The musculofibrous partition that separates the thoracic cavity from the abdominal cavity. Contraction of the diaphragm increases the volume of the thoracic cavity aiding inspiration. [NIH] Diarrhoea: Abnormal frequency and liquidity of faecal discharges. [EU] Diastolic: Of or pertaining to the diastole. [EU] Diclofenac: A non-steroidal anti-inflammatory agent (NSAID) with antipyretic and analgesic actions. It is primarily available as the sodium salt, diclofenac sodium. [NIH] Diclofenac Sodium: The sodium form of diclofenac. It is used for its analgesic and antiinflammatory properties. [NIH] Diencephalon: The paired caudal parts of the prosencephalon from which the thalamus, hypothalamus, epithalamus, and subthalamus are derived. [NIH] 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] Diffusivity: Of a reverberant sound field. The degree to which the directions of propagation of waves are random from point to point. [NIH] Digestion: The process of breakdown of food for metabolism and use by the body. [NIH]
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Digestive system: The organs that take in food and turn it into products that the body can use to stay healthy. Waste products the body cannot use leave the body through bowel movements. The digestive system includes the salivary glands, mouth, esophagus, stomach, liver, pancreas, gallbladder, small and large intestines, and rectum. [NIH] Digestive tract: The organs through which food passes when food is eaten. These organs are the mouth, esophagus, stomach, small and large intestines, and rectum. [NIH] Dilatation: The act of dilating. [NIH] Dimethyl: A volatile metabolite of the amino acid methionine. [NIH] Dipeptides: Peptides composed of two amino acid units. [NIH] Diphenhydramine: A histamine H1 antagonist used as an antiemetic, antitussive, for dermatoses and pruritus, for hypersensitivity reactions, as a hypnotic, an antiparkinson, and as an ingredient in common cold preparations. It has some undesired antimuscarinic and sedative effects. [NIH] 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] Disaccharides: Sugars composed of two monosaccharides linked by glycoside bonds. [NIH] Disease Progression: The worsening of a disease over time. This concept is most often used for chronic and incurable diseases where the stage of the disease is an important determinant of therapy and prognosis. [NIH] Disinfectant: An agent that disinfects; applied particularly to agents used on inanimate objects. [EU] Dissection: Cutting up of an organism for study. [NIH] Dissociation: 1. The act of separating or state of being separated. 2. The separation of a molecule into two or more fragments (atoms, molecules, ions, or free radicals) produced by the absorption of light or thermal energy or by solvation. 3. In psychology, a defense mechanism in which a group of mental processes are segregated from the rest of a person's mental activity in order to avoid emotional distress, as in the dissociative disorders (q.v.), or in which an idea or object is segregated from its emotional significance; in the first sense it is roughly equivalent to splitting, in the second, to isolation. 4. A defect of mental integration in which one or more groups of mental processes become separated off from normal consciousness and, thus separated, function as a unitary whole. [EU] Dissociative Disorders: Sudden temporary alterations in the normally integrative functions of consciousness. [NIH] Distal: Remote; farther from any point of reference; opposed to proximal. In dentistry, used to designate a position on the dental arch farther from the median line of the jaw. [EU] Diuresis: Increased excretion of urine. [EU] Diuretic: A drug that increases the production of urine. [NIH] Domesticated: Species in which the evolutionary process has been influenced by humans to meet their needs. [NIH] Dopamine: An endogenous catecholamine and prominent neurotransmitter in several systems of the brain. In the synthesis of catecholamines from tyrosine, it is the immediate precursor to norepinephrine and epinephrine. Dopamine is a major transmitter in the extrapyramidal system of the brain, and important in regulating movement. A family of dopaminergic receptor subtypes mediate its action. Dopamine is used pharmacologically for its direct (beta adrenergic agonist) and indirect (adrenergic releasing) sympathomimetic
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effects including its actions as an inotropic agent and as a renal vasodilator. [NIH] Dorsal: 1. Pertaining to the back or to any dorsum. 2. Denoting a position more toward the back surface than some other object of reference; same as posterior in human anatomy; superior in the anatomy of quadrupeds. [EU] Dorsum: A plate of bone which forms the posterior boundary of the sella turcica. [NIH] Dosage Forms: Completed forms of the pharmaceutical preparation in which prescribed doses of medication are included. They are designed to resist action by gastric fluids, prevent vomiting and nausea, reduce or alleviate the undesirable taste and smells associated with oral administration, achieve a high concentration of drug at target site, or produce a delayed or long-acting drug effect. They include capsules, liniments, ointments, pharmaceutical solutions, powders, tablets, etc. [NIH] Dose-limiting: Describes side effects of a drug or other treatment that are serious enough to prevent an increase in dose or level of that treatment. [NIH] Double-blinded: A clinical trial in which neither the medical staff nor the person knows which of several possible therapies the person is receiving. [NIH] Doxorubicin: Antineoplastic antibiotic obtained from Streptomyces peucetics. It is a hydroxy derivative of daunorubicin and is used in treatment of both leukemia and solid tumors. [NIH] Drive: A state of internal activity of an organism that is a necessary condition before a given stimulus will elicit a class of responses; e.g., a certain level of hunger (drive) must be present before food will elicit an eating response. [NIH] Drug Interactions: The action of a drug that may affect the activity, metabolism, or toxicity of another drug. [NIH] Duct: A tube through which body fluids pass. [NIH] Duodenum: The first part of the small intestine. [NIH] Dura mater: The outermost, toughest, and most fibrous of the three membranes (meninges) covering the brain and spinal cord; called also pachymeninx. [EU] Dyes: Chemical substances that are used to stain and color other materials. The coloring may or may not be permanent. Dyes can also be used as therapeutic agents and test reagents in medicine and scientific research. [NIH] Dyspareunia: Painful sexual intercourse. [NIH] Dysplasia: Cells that look abnormal under a microscope but are not cancer. [NIH] Dyspnea: Difficult or labored breathing. [NIH] Dystrophic: Pertaining to toxic habitats low in nutrients. [NIH] Dystrophy: Any disorder arising from defective or faulty nutrition, especially the muscular dystrophies. [EU] Echinacea: A genus of perennial herbs used topically and internally. It contains echinacoside, glycosides, inulin, isobutyl amides, resin, and sesquiterpenes. [NIH] Ectoderm: The outer of the three germ layers of the embryo. [NIH] Eczema: A pruritic papulovesicular dermatitis occurring as a reaction to many endogenous and exogenous agents (Dorland, 27th ed). [NIH] Effector: It is often an enzyme that converts an inactive precursor molecule into an active second messenger. [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
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based on the results of a randomized control trial. [NIH] Effusion: The escape of fluid into a part or tissue, as an exudation or a transudation. [EU] Elasticity: Resistance and recovery from distortion of shape. [NIH] Elastin: The protein that gives flexibility to tissues. [NIH] Electrocoagulation: Electrosurgical procedures used to treat hemorrhage (e.g., bleeding ulcers) and to ablate tumors, mucosal lesions, and refractory arrhythmias. [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 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] Embryo: The prenatal stage of mammalian development characterized by rapid morphological changes and the differentiation of basic structures. [NIH] Embryogenesis: The process of embryo or embryoid formation, whether by sexual (zygotic) or asexual means. In asexual embryogenesis embryoids arise directly from the explant or on intermediary callus tissue. In some cases they arise from individual cells (somatic cell embryoge). [NIH] Emollient: Softening or soothing; called also malactic. [EU] Empirical: A treatment based on an assumed diagnosis, prior to receiving confirmatory laboratory test results. [NIH] Emulsion: A preparation of one liquid distributed in small globules throughout the body of a second liquid. The dispersed liquid is the discontinuous phase, and the dispersion medium is the continuous phase. When oil is the dispersed liquid and an aqueous solution is the continuous phase, it is known as an oil-in-water emulsion, whereas when water or aqueous solution is the dispersed phase and oil or oleaginous substance is the continuous phase, it is known as a water-in-oil emulsion. Pharmaceutical emulsions for which official standards have been promulgated include cod liver oil emulsion, cod liver oil emulsion with malt, liquid petrolatum emulsion, and phenolphthalein in liquid petrolatum emulsion. [EU] 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]
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Endocytosis: Cellular uptake of extracellular materials within membrane-limited vacuoles or microvesicles. Endosomes play a central role in endocytosis. [NIH] Endopeptidases: A subclass of peptide hydrolases. They are classified primarily by their catalytic mechanism. Specificity is used only for identification of individual enzymes. They comprise the serine endopeptidases, EC 3.4.21; cysteine endopeptidases, EC 3.4.22; aspartic endopeptidases, EC 3.4.23, metalloendopeptidases, EC 3.4.24; and a group of enzymes yet to be assigned to any of the above sub-classes, EC 3.4.99. EC 3.4.-. [NIH] Endorphin: Opioid peptides derived from beta-lipotropin. Endorphin is the most potent naturally occurring analgesic agent. It is present in pituitary, brain, and peripheral tissues. [NIH]
Endothelial cell: The main type of cell found in the inside lining of blood vessels, lymph vessels, and the heart. [NIH] Endothelium: A layer of epithelium that lines the heart, blood vessels (endothelium, vascular), lymph vessels (endothelium, lymphatic), and the serous cavities of the body. [NIH] Endothelium-derived: Small molecule that diffuses to the adjacent muscle layer and relaxes it. [NIH] Endotoxins: Toxins closely associated with the living cytoplasm or cell wall of certain microorganisms, which do not readily diffuse into the culture medium, but are released upon lysis of the cells. [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] Enteropeptidase: A specialized proteolytic enzyme secreted by intestinal cells. It converts trypsinogen into its active form trypsin by removing the N-terminal peptide. EC 3.4.21.9. [NIH]
Entorhinal Cortex: Cortex where the signals are combined with those from other sensory systems. [NIH] Environmental Exposure: The exposure to potentially harmful chemical, physical, or biological agents in the environment or to environmental factors that may include ionizing radiation, pathogenic organisms, or toxic chemicals. [NIH] Environmental Health: The science of controlling or modifying those conditions, influences, or forces surrounding man which relate to promoting, establishing, and maintaining health. [NIH]
Enzymatic: Phase where enzyme cuts the precursor protein. [NIH] Enzyme: A protein that speeds up chemical reactions in the body. [NIH] Enzyme 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] Eosinophil: A polymorphonuclear leucocyte with large eosinophilic granules in its cytoplasm, which plays a role in hypersensitivity reactions. [NIH] 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]
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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] Epidermolysis Bullosa: Group of genetically determined disorders characterized by the blistering of skin and mucosae. There are four major forms: acquired, simple, junctional, and dystrophic. Each of the latter three has several varieties. [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] Epiphyseal: Pertaining to or of the nature of an epiphysis. [EU] Epiphyses: The head of a long bone that is separated from the shaft by the epiphyseal plate until bone growth stops. At that time, the plate disappears and the head and shaft are united. [NIH] Episcleritis: Inflammation of the episclera and/or the outer layers of the sclera itself. [NIH] Epithelial: Refers to the cells that line the internal and external surfaces of the body. [NIH] Epithelial Cells: Cells that line the inner and outer surfaces of the body. [NIH] Epithelium: One or more layers of epithelial cells, supported by the basal lamina, which covers the inner or outer surfaces of the body. [NIH] Epitope: A molecule or portion of a molecule capable of binding to the combining site of an antibody. For every given antigenic determinant, the body can construct a variety of antibody-combining sites, some of which fit almost perfectly, and others which barely fit. [NIH]
Erythrocyte Membrane: The semipermeable outer portion of the red corpuscle. It is known as a 'ghost' after hemolysis. [NIH] Erythrocytes: Red blood cells. Mature erythrocytes are non-nucleated, biconcave disks containing hemoglobin whose function is to transport oxygen. [NIH] 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] Estrogen receptor: ER. Protein found on some cancer cells to which estrogen will attach. [NIH]
Estrogen Replacement Therapy: The use of hormonal agents with estrogen-like activity in postmenopausal or other estrogen-deficient women to alleviate effects of hormone deficiency, such as vasomotor symptoms, dyspareunia, and progressive development of osteoporosis. This may also include the use of progestational agents in combination therapy. [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]
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Ethmoid: An unpaired cranial bone which helps form the medial walls of the orbits and contains the themoidal air cells which drain into the nose. [NIH] Eukaryotic Cells: Cells of the higher organisms, containing a true nucleus bounded by a nuclear membrane. [NIH] Evacuation: An emptying, as of the bowels. [EU] Evoke: The electric response recorded from the cerebral cortex after stimulation of a peripheral sense organ. [NIH] Excipient: Any more or less inert substance added to a prescription in order to confer a suitable consistency or form to the drug; a vehicle. [EU] Excrete: To get rid of waste from the body. [NIH] Exhaustion: The feeling of weariness of mind and body. [NIH] Exogenous: Developed or originating outside the organism, as exogenous disease. [EU] Exostoses: Benign hypertrophy that projects outward from the surface of bone, often containing a cartilaginous component. [NIH] Extensor: A muscle whose contraction tends to straighten a limb; the antagonist of a flexor. [NIH]
External-beam radiation: Radiation therapy that uses a machine to aim high-energy rays at the cancer. Also called external radiation. [NIH] Extracellular: Outside a cell or cells. [EU] Extracellular Matrix: A meshwork-like substance found within the extracellular space and in association with the basement membrane of the cell surface. It promotes cellular proliferation and provides a supporting structure to which cells or cell lysates in culture dishes adhere. [NIH] Extracellular Matrix Proteins: Macromolecular organic compounds that contain carbon, hydrogen, oxygen, nitrogen, and usually, sulfur. These macromolecules (proteins) form an intricate meshwork in which cells are embedded to construct tissues. Variations in the relative types of macromolecules and their organization determine the type of extracellular matrix, each adapted to the functional requirements of the tissue. The two main classes of 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] Extraction: The process or act of pulling or drawing out. [EU] Extrapyramidal: Outside of the pyramidal tracts. [EU] Exudate: Material, such as fluid, cells, or cellular debris, which has escaped from blood vessels and has been deposited in tissues or on tissue surfaces, usually as a result of inflammation. An exudate, in contrast to a transudate, is characterized by a high content of protein, cells, or solid materials derived from cells. [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] Family Planning: Programs or services designed to assist the family in controlling reproduction by either improving or diminishing fertility. [NIH]
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Fat: Total lipids including phospholipids. [NIH] Fatigue: The state of weariness following a period of exertion, mental or physical, characterized by a decreased capacity for work and reduced efficiency to respond to stimuli. [NIH]
Fatty acids: A major component of fats that are used by the body for energy and tissue development. [NIH] Feces: The excrement discharged from the intestines, consisting of bacteria, cells exfoliated from the intestines, secretions, chiefly of the liver, and a small amount of food residue. [EU] Femoral: Pertaining to the femur, or to the thigh. [EU] Femoral Artery: The main artery of the thigh, a continuation of the external iliac artery. [NIH] Femur: The longest and largest bone of the skeleton, it is situated between the hip and the knee. [NIH] Fertilizers: Substances or mixtures that are added to the soil to supply nutrients or to make available nutrients already present in the soil, in order to increase plant growth and productivity. [NIH] Fetus: The developing offspring from 7 to 8 weeks after conception until birth. [NIH] Fibril: Most bacterial viruses have a hollow tail with specialized fibrils at its tip. The tail fibers attach to the cell wall of the host. [NIH] Fibrin: A protein derived from fibrinogen in the presence of thrombin, which forms part of the blood clot. [NIH] Fibrinogen: Plasma glycoprotein clotted by thrombin, composed of a dimer of three nonidentical pairs of polypeptide chains (alpha, beta, gamma) held together by disulfide bonds. Fibrinogen clotting is a sol-gel change involving complex molecular arrangements: whereas fibrinogen is cleaved by thrombin to form polypeptides A and B, the proteolytic action of other enzymes yields different fibrinogen degradation products. [NIH] 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] Fibronectin: An adhesive glycoprotein. One form circulates in plasma, acting as an opsonin; another is a cell-surface protein which mediates cellular adhesive interactions. [NIH] Fibrosis: Any pathological condition where fibrous connective tissue invades any organ, usually as a consequence of inflammation or other injury. [NIH] Fibrotic tissue: Inflamed tissue that has become scarred. [NIH] Flatus: Gas passed through the rectum. [NIH] Flavoring Agents: Substances added to foods and medicine to improve the quality of taste. [NIH]
Flexor: Muscles which flex a joint. [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] Folate: A B-complex vitamin that is being studied as a cancer prevention agent. Also called
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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] Food Additives: Substances which are of little or no nutritive value, but are used in the processing or storage of foods or animal feed, especially in the developed countries; includes antioxidants, food preservatives, food coloring agents, flavoring agents, anti-infective agents (both plain and local), vehicles, excipients and other similarly used substances. Many of the same substances are pharmaceutic aids when added to pharmaceuticals rather than to foods. [NIH]
Food Coloring Agents: Natural or synthetic dyes used as coloring agents in processed foods. [NIH] Food Preservatives: Substances capable of inhibiting, retarding or arresting the process of fermentation, acidification or other deterioration of foods. [NIH] Foramen: A natural hole of perforation, especially one in a bone. [NIH] Fractionation: Dividing the total dose of radiation therapy into several smaller, equal doses delivered over a period of several days. [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] Fucose: Deoxysugar. [NIH] Fungi: A kingdom of eukaryotic, heterotrophic organisms that live as saprobes or parasites, including mushrooms, yeasts, smuts, molds, etc. They reproduce either sexually or asexually, and have life cycles that range from simple to complex. Filamentous fungi refer to those that grow as multicelluar colonies (mushrooms and molds). [NIH] Fungistatic: Inhibiting the growth of fungi. [EU] Gait: Manner or style of walking. [NIH] Gallbladder: The pear-shaped organ that sits below the liver. Bile is concentrated and stored in the gallbladder. [NIH] Gallstones: The solid masses or stones made of cholesterol or bilirubin that form in the gallbladder or bile ducts. [NIH] Gamma irradiation: A type of radiation therapy that uses gamma radiation. Gamma radiation is a type of high-energy radiation that is different from x-rays. [NIH] Gamma-Endorphin: An endogenous opioid peptide derived from the pro-opiomelanocortin precursor peptide. It differs from alpha-endorphin by one amino acid. [NIH] Ganglia: Clusters of multipolar neurons surrounded by a capsule of loosely organized connective tissue located outside the central nervous system. [NIH] Ganglion: 1. A knot, or knotlike mass. 2. A general term for a group of nerve cell bodies located outside the central nervous system; occasionally applied to certain nuclear groups within the brain or spinal cord, e.g. basal ganglia. 3. A benign cystic tumour occurring on a aponeurosis or tendon, as in the wrist or dorsum of the foot; it consists of a thin fibrous capsule enclosing a clear mucinous fluid. [EU] Gap Junctions: Connections between cells which allow passage of small molecules and electric current. Gap junctions were first described anatomically as regions of close
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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] Gastric: Having to do with the stomach. [NIH] Gastric Acid: Hydrochloric acid present in gastric juice. [NIH] Gastrin: A hormone released after eating. Gastrin causes the stomach to produce more acid. [NIH]
Gastrointestinal: Refers to the stomach and intestines. [NIH] Gastrointestinal tract: The stomach and intestines. [NIH] Gelatin: A product formed from skin, white connective tissue, or bone collagen. It is used as a protein food adjuvant, plasma substitute, hemostatic, suspending agent in pharmaceutical preparations, and in the manufacturing of capsules and suppositories. [NIH] Gelatinase A: A secreted endopeptidase homologous with interstitial collagenase, but which possesses an additional fibronectin-like domain. EC 3.4.24.24. [NIH] Gelatinases: A class of enzymes that catalyzes the degradation of gelatin by acting on the peptide bonds. EC 3.4.24.-. [NIH] Gels: Colloids with a solid continuous phase and liquid as the dispersed phase; gels may be unstable when, due to temperature or other cause, the solid phase liquifies; the resulting colloid is called a sol. [NIH] Gelsolin: A 90-kD protein produced by macrophages that severs actin filaments and forms a cap on the newly exposed filament end. Gelsolin is activated by calcium ions and participates in the assembly and disassembly of actin, thereby increasing the motility of some cells. [NIH] Gene: The functional and physical unit of heredity passed from parent to offspring. Genes are pieces of DNA, and most genes contain the information for making a specific protein. [NIH]
Gene Expression: The phenotypic manifestation of a gene or genes by the processes of gene action. [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 Screening: Searching a population or individuals for persons possessing certain genotypes or karyotypes that: (1) are already associated with disease or predispose to disease; (2) may lead to disease in their descendants; or (3) produce other variations not known to be associated with disease. Genetic screening may be directed toward identifying phenotypic expression of genetic traits. It includes prenatal genetic screening. [NIH] Genetics: The biological science that deals with the phenomena and mechanisms of
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heredity. [NIH] Genotype: The genetic constitution of the individual; the characterization of the genes. [NIH] Germ Cells: The reproductive cells in multicellular organisms. [NIH] Gestation: The period of development of the young in viviparous animals, from the time of fertilization of the ovum until birth. [EU] Gland: An organ that produces and releases one or more substances for use in the body. Some glands produce fluids that affect tissues or organs. Others produce hormones or participate in blood production. [NIH] Glomerular: Pertaining to or of the nature of a glomerulus, especially a renal glomerulus. [EU]
Glomeruli: Plural of glomerulus. [NIH] Glomerulus: A tiny set of looping blood vessels in the nephron where blood is filtered in the kidney. [NIH] 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] Glucuronate: Salt of glucuronic acid. [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] Glutamic Acid: A non-essential amino acid naturally occurring in the L-form. Glutamic acid (glutamate) is the most common excitatory neurotransmitter in the central nervous system. [NIH]
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]
Glycine: A non-essential amino acid. It is found primarily in gelatin and silk fibroin and used therapeutically as a nutrient. It is also a fast inhibitory neurotransmitter. [NIH] Glycogen: A sugar stored in the liver and muscles. It releases glucose into the blood when cells need it for energy. Glycogen is the chief source of stored fuel in the body. [NIH] Glycoprotein: A protein that has sugar molecules attached to it. [NIH] Glycosaminoglycan: A type of long, unbranched polysaccharide molecule. Glycosaminoglycans are major structural components of cartilage and are also found in the cornea of the eye. [NIH] Glycoside: Any compound that contains a carbohydrate molecule (sugar), particularly any such natural product in plants, convertible, by hydrolytic cleavage, into sugar and a nonsugar component (aglycone), and named specifically for the sugar contained, as glucoside (glucose), pentoside (pentose), fructoside (fructose) etc. [EU] Glycosidic: Formed by elimination of water between the anomeric hydroxyl of one sugar and a hydroxyl of another sugar molecule. [NIH] Glycosylation: The chemical or biochemical addition of carbohydrate or glycosyl groups to
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other chemicals, especially peptides or proteins. Glycosyl transferases are used in this biochemical reaction. [NIH] Gonad: A sex organ, such as an ovary or a testicle, which produces the gametes in most multicellular animals. [NIH] Gonadal: Pertaining to a gonad. [EU] 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 its membrane receptor, the CD4 molecule, found on the surface of certain cells in the body. [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] Graft Survival: The survival of a graft in a host, the factors responsible for the survival and the changes occurring within the graft during growth in the host. [NIH] Grafting: The operation of transfer of tissue from one site to another. [NIH] Granule: A small pill made from sucrose. [EU] Granulocytes: Leukocytes with abundant granules in the cytoplasm. They are divided into three groups: neutrophils, eosinophils, and basophils. [NIH] 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] Gravidity: Pregnancy; the condition of being pregnant, without regard to the outcome. [EU] Growth: The progressive development of a living being or part of an organism from its earliest stage to maturity. [NIH] Growth Cones: Bulbous enlargement of the growing tip of nerve axons and dendrites. They are crucial to neuronal development because of their pathfinding ability and their role in synaptogenesis. [NIH] Growth factors: Substances made by the body that function to regulate cell division and cell survival. Some growth factors are also produced in the laboratory and used in biological therapy. [NIH] Growth Plate: The area between the epiphysis and the diaphysis within which bone growth occurs. [NIH] Guanylate Cyclase: An enzyme that catalyzes the conversion of GTP to 3',5'-cyclic GMP and pyrophosphate. It also acts on ITP and dGTP. (From Enzyme Nomenclature, 1992) EC 4.6.1.2. [NIH] Gum Arabic: Powdered exudate from various Acacia species, especially A. senegal (Leguminosae). It forms mucilage or syrup in water. Gum arabic is used as a suspending agent, excipient, and emulsifier in foods and pharmaceuticals. [NIH] Haemodialysis: The removal of certain elements from the blood by virtue of the difference in the rates of their diffusion through a semipermeable membrane, e.g., by means of a
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haemodialyzer. [EU] Hair Color: Color of hair or fur. [NIH] Hair Dyes: Dyes used as cosmetics to change hair color either permanently or temporarily. [NIH]
Half-Life: The time it takes for a substance (drug, radioactive nuclide, or other) to lose half of its pharmacologic, physiologic, or radiologic activity. [NIH] Haploid: An organism with one basic chromosome set, symbolized by n; the normal condition of gametes in diploids. [NIH] Haptens: Small antigenic determinants capable of eliciting an immune response only when coupled to a carrier. Haptens bind to antibodies but by themselves cannot elicit an antibody response. [NIH] Headache: Pain in the cranial region that may occur as an isolated and benign symptom or as a manifestation of a wide variety of conditions including subarachnoid hemorrhage; craniocerebral trauma; central nervous system infections; intracranial hypertension; and other disorders. In general, recurrent headaches that are not associated with a primary disease process are referred to as headache disorders (e.g., migraine). [NIH] Health Promotion: Encouraging consumer behaviors most likely to optimize health potentials (physical and psychosocial) through health information, preventive programs, and access to medical care. [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 Valves: Flaps of tissue that prevent regurgitation of blood from the ventricles to the atria or from the pulmonary arteries or aorta to the ventricles. [NIH] Heat-Shock Proteins: Proteins which are synthesized in eukaryotic organisms and bacteria in response to hyperthermia and other environmental stresses. They increase thermal tolerance and perform functions essential to cell survival under these conditions. [NIH] Heat-Shock Proteins 90: A class of molecular chaperones whose members act in the mechanism of signal transduction by steroid receptors. [NIH] Hematogenous: Originating in the blood or spread through the bloodstream. [NIH] Hematology: A subspecialty of internal medicine concerned with morphology, physiology, and pathology of the blood and blood-forming tissues. [NIH] Hematopoietic Stem Cells: Progenitor cells from which all blood cells derive. [NIH] Hemodiafiltration: The combination of hemodialysis and hemofiltration either simultaneously or sequentially. Convective transport (hemofiltration) may be better for removal of larger molecular weight substances and diffusive transport (hemodialysis) for smaller molecular weight solutes. [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] Hemofiltration: Extracorporeal ultrafiltration technique without hemodialysis for treatment of fluid overload and electrolyte disturbances affecting renal, cardiac, or pulmonary function. [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
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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] Hemolysis: The destruction of erythrocytes by many different causal agents such as antibodies, bacteria, chemicals, temperature, and changes in tonicity. [NIH] Hemorrhage: Bleeding or escape of blood from a vessel. [NIH] Hemostasis: The process which spontaneously arrests the flow of blood from vessels carrying blood under pressure. It is accomplished by contraction of the vessels, adhesion and aggregation of formed blood elements, and the process of blood or plasma coagulation. [NIH]
Heparan Sulfate Proteoglycan: A substance released by astrocytes, which is critical in stopping nervous fibers in their tracks. [NIH] Heparin: Heparinic acid. A highly acidic mucopolysaccharide formed of equal parts of sulfated D-glucosamine and D-glucuronic acid with sulfaminic bridges. The molecular weight ranges from six to twenty thousand. Heparin occurs in and is obtained from liver, lung, mast cells, etc., of vertebrates. Its function is unknown, but it is used to prevent blood clotting in vivo and vitro, in the form of many different salts. [NIH] Hepatic: Refers to the liver. [NIH] Hepatobiliary: Pertaining to the liver and the bile or the biliary ducts. [EU] Hepatocyte: A liver cell. [NIH] Hepatocyte Growth Factor: Multifunctional growth factor which regulates both cell growth and cell motility. It exerts a strong mitogenic effect on hepatocytes and primary epithelial cells. Its receptor is proto-oncogene protein C-met. [NIH] Hereditary: Of, relating to, or denoting factors that can be transmitted genetically from one generation to another. [NIH] Heredity: 1. The genetic transmission of a particular quality or trait from parent to offspring. 2. The genetic constitution of an individual. [EU] Heterodimers: Zippered pair of nonidentical proteins. [NIH] Heterogeneity: The property of one or more samples or populations which implies that they are not identical in respect of some or all of their parameters, e. g. heterogeneity of variance. [NIH]
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] Hirudin: The active principle in the buccal gland secretion of leeches. It acts as an antithrombin and as an antithrombotic agent. [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]
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Histidine: An essential amino acid important in a number of metabolic processes. It is required for the production of histamine. [NIH] Histology: The study of tissues and cells under a microscope. [NIH] Homeostasis: The processes whereby the internal environment of an organism tends to remain balanced and stable. [NIH] Homodimer: Protein-binding "activation domains" always combine with identical proteins. [NIH]
Homogeneous: Consisting of or composed of similar elements or ingredients; of a uniform quality throughout. [EU] Homologous: Corresponding in structure, position, origin, etc., as (a) the feathers of a bird and the scales of a fish, (b) antigen and its specific antibody, (c) allelic chromosomes. [EU] Hormonal: Pertaining to or of the nature of a hormone. [EU] Hormone: A substance in the body that regulates certain organs. Hormones such as gastrin help in breaking down food. Some hormones come from cells in the stomach and small intestine. [NIH] Horny layer: The superficial layer of the epidermis containing keratinized cells. [NIH] Host: Any animal that receives a transplanted graft. [NIH] 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] Hyaluronidase: An enzyme that splits hyaluronic acid and thus lowers the viscosity of the acid and facilitates the spreading of fluids through tissues either advantageously or disadvantageously. [NIH] Hybrid: Cross fertilization between two varieties or, more usually, two species of vines, see also crossing. [NIH] Hybridization: The genetic process of crossbreeding to produce a hybrid. Hybrid nucleic acids can be formed by nucleic acid hybridization of DNA and RNA molecules. Protein hybridization allows for hybrid proteins to be formed from polypeptide chains. [NIH] Hydration: Combining with water. [NIH] Hydrofluoric Acid: A solution of hydrogen fluoride in water. It is a colorless fuming liquid which can cause painful burns. [NIH] Hydrogel: A network of cross-linked hydrophilic macromolecules used in biomedical applications. [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] Hydrolysis: The process of cleaving a chemical compound by the addition of a molecule of water. [NIH] Hydrophilic: Readily absorbing moisture; hygroscopic; having strongly polar groups that readily interact with water. [EU] Hydrophobic: Not readily absorbing water, or being adversely affected by water, as a
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hydrophobic colloid. [EU] Hydroxylation: Hydroxylate, to introduce hydroxyl into (a compound or radical) usually by replacement of hydrogen. [EU] Hydroxylysine: A hydroxylated derivative of the amino acid lysine that is present in certain collagens. [NIH] Hydroxyproline: A hydroxylated form of the imino acid proline. A deficiency in ascorbic acid can result in impaired hydroxyproline formation. [NIH] Hydroxyzine: A histamine H1 receptor antagonist that is effective in the treatment of chronic urticaria, dermatitis, and histamine-mediated pruritus. Unlike its major metabolite cetirizine, it does cause drowsiness. It is also effective as an antiemetic, for relief of anxiety and tension, and as a sedative. [NIH] Hygienic: Pertaining to hygiene, or conducive to health. [EU] Hyperkeratosis: 1. Hypertrophy of the corneous layer of the skin. 2a. Any of various conditions marked by hyperkeratosis. 2b. A disease of cattle marked by thickening and wringling of the hide and formation of papillary outgrowths on the buccal mucous membranes, often accompanied by watery discharge from eyes and nose, diarrhoea, loss of condition, and abortion of pregnant animals, and now believed to result from ingestion of the chlorinated naphthalene of various lubricating oils. [EU] Hyperopia: Farsightedness; ability to see distant objects more clearly than close objects; may be corrected with glasses or contact lenses. [NIH] Hyperplasia: An increase in the number of cells in a tissue or organ, not due to tumor formation. It differs from hypertrophy, which is an increase in bulk without an increase in the number of cells. [NIH] Hypersensitivity: Altered reactivity to an antigen, which can result in pathologic reactions upon subsequent exposure to that particular antigen. [NIH] Hypertension: Persistently high arterial blood pressure. Currently accepted threshold levels are 140 mm Hg systolic and 90 mm Hg diastolic pressure. [NIH] Hypertrophy: General increase in bulk of a part or organ, not due to tumor formation, nor to an increase in the number of cells. [NIH] Hyperuricemia: A buildup of uric acid (a byproduct of metabolism) in the blood; a side effect of some anticancer drugs. [NIH] Hypervitaminosis: A condition due to ingestion of an excess of one or more vitamins; called also supervitaminosis. [EU] Hypesthesia: Absent or reduced sensitivity to cutaneous stimulation. [NIH] Hypnotic: A drug that acts to induce sleep. [EU] Hypoplasia: Incomplete development or underdevelopment of an organ or tissue. [EU] Hypotensive: Characterized by or causing diminished tension or pressure, as abnormally low blood pressure. [EU] Hypothermia: Lower than normal body temperature, especially in warm-blooded animals; in man usually accidental or unintentional. [NIH] Ichthyosis: Any of several generalized skin disorders characterized by dryness, roughness, and scaliness, due to hypertrophy of the stratum corneum epidermis. Most are genetic, but some are acquired, developing in association with other systemic disease or genetic syndrome. [NIH] Id: The part of the personality structure which harbors the unconscious instinctive desires
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and strivings of the individual. [NIH] Idiopathic: Describes a disease of unknown cause. [NIH] Iduronic Acid: Component of dermatan sulfate. Differs in configuration from glucuronic acid only at the C-5 position. [NIH] Immaturity: The state or quality of being unripe or not fully developed. [EU] 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
Immunocompromised: Having a weakened immune system caused by certain diseases or treatments. [NIH] Immunoconjugates: Combinations of diagnostic or therapeutic substances linked with specific immune substances such as immunoglobulins, monoclonal antibodies or antigens. Often the diagnostic or therapeutic substance is a radionuclide. These conjugates are useful tools for specific targeting of drugs and radioisotopes in the chemotherapy and radioimmunotherapy of certain cancers. [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] Immunohistochemistry: Histochemical localization of immunoreactive substances using labeled antibodies as reagents. [NIH] Immunology: The study of the body's immune system. [NIH] Immunophilin: A drug for the treatment of Parkinson's disease. [NIH] Immunosuppressive: Describes the ability to lower immune system responses. [NIH] Immunosuppressive Agents: Agents that suppress immune function by one of several mechanisms of action. Classical cytotoxic immunosuppressants act by inhibiting DNA synthesis. Others may act through activation of suppressor T-cell populations or by inhibiting the activation of helper cells. While immunosuppression has been brought about in the past primarily to prevent rejection of transplanted organs, new applications involving mediation of the effects of interleukins and other cytokines are emerging. [NIH] Impairment: In the context of health experience, an impairment is any loss or abnormality of psychological, physiological, or anatomical structure or function. [NIH] Implant radiation: A procedure in which radioactive material sealed in needles, seeds, wires, or catheters is placed directly into or near the tumor. Also called [NIH] Implantation: The insertion or grafting into the body of biological, living, inert, or radioactive material. [EU] In situ: In the natural or normal place; confined to the site of origin without invasion of neighbouring tissues. [EU] In Situ Hybridization: A technique that localizes specific nucleic acid sequences within intact chromosomes, eukaryotic cells, or bacterial cells through the use of specific nucleic acid-labeled probes. [NIH]
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In vitro: In the laboratory (outside the body). The opposite of in vivo (in the body). [NIH] In vivo: In the body. The opposite of in vitro (outside the body or in the laboratory). [NIH] Incision: A cut made in the body during surgery. [NIH] Incubation: The development of an infectious disease from the entrance of the pathogen to the appearance of clinical symptoms. [EU] Indicative: That indicates; that points out more or less exactly; that reveals fairly clearly. [EU] Induction: The act or process of inducing or causing to occur, especially the production of a specific morphogenetic effect in the developing embryo through the influence of evocators or organizers, or the production of anaesthesia or unconsciousness by use of appropriate agents. [EU] Infarction: A pathological process consisting of a sudden insufficient blood supply to an area, which results in necrosis of that area. It is usually caused by a thrombus, an embolus, or a vascular torsion. [NIH] Infection: 1. Invasion and multiplication of microorganisms in body tissues, which may be 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]
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] Infuse: To pour (a liquid) into something. [EU] Ingestion: Taking into the body by mouth [NIH] Inhalation: The drawing of air or other substances into the lungs. [EU] Initiation: Mutation induced by a chemical reactive substance causing cell changes; being a step in a carcinogenic process. [NIH] Inlay: In dentistry, a filling first made to correspond with the form of a dental cavity and then cemented into the cavity. [NIH] Innervation: 1. The distribution or supply of nerves to a part. 2. The supply of nervous energy or of nerve stimulus sent to a part. [EU] Inorganic: Pertaining to substances not of organic origin. [EU] Inositol: An isomer of glucose that has traditionally been considered to be a B vitamin although it has an uncertain status as a vitamin and a deficiency syndrome has not been identified in man. (From Martindale, The Extra Pharmacopoeia, 30th ed, p1379) Inositol phospholipids are important in signal transduction. [NIH] Inositol 1,4,5-Trisphosphate: Intracellular messenger formed by the action of phospholipase C on phosphatidylinositol 4,5-bisphosphate, which is one of the phospholipids that make up the cell membrane. Inositol 1,4,5-trisphosphate is released into the cytoplasm where it releases calcium ions from internal stores within the cell's endoplasmic reticulum. These calcium ions stimulate the activity of B kinase or calmodulin. [NIH] Inotropic: Affecting the force or energy of muscular contractions. [EU] Insertional: A technique in which foreign DNA is cloned into a restriction site which occupies a position within the coding sequence of a gene in the cloning vector molecule.
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Insertion interrupts the gene's sequence such that its original function is no longer expressed. [NIH] Insight: The capacity to understand one's own motives, to be aware of one's own psychodynamics, to appreciate the meaning of symbolic behavior. [NIH] Instillation: . [EU] Insulator: Material covering the metal conductor of the lead. It is usually polyurethane or silicone. [NIH] Insulin: A protein hormone secreted by beta cells of the pancreas. Insulin plays a major role in the regulation of glucose metabolism, generally promoting the cellular utilization of glucose. It is also an important regulator of protein and lipid metabolism. Insulin is used as a drug to control insulin-dependent diabetes mellitus. [NIH] Insulin-dependent diabetes mellitus: A disease characterized by high levels of blood glucose resulting from defects in insulin secretion, insulin action, or both. Autoimmune, genetic, and environmental factors are involved in the development of type I diabetes. [NIH] Integrins: A family of transmembrane glycoproteins consisting of noncovalent heterodimers. They interact with a wide variety of ligands including extracellular matrix glycoproteins, complement, and other cells, while their intracellular domains interact with the cytoskeleton. The integrins consist of at least three identified families: the cytoadhesin receptors, the leukocyte adhesion receptors, and the very-late-antigen receptors. Each family contains a common beta-subunit combined with one or more distinct alpha-subunits. These receptors participate in cell-matrix and cell-cell adhesion in many physiologically important processes, including embryological development, hemostasis, thrombosis, wound healing, immune and nonimmune defense mechanisms, and oncogenic transformation. [NIH] 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-8: A cytokine that activates neutrophils and attracts neutrophils and Tlymphocytes. It is released by several cell types including monocytes, macrophages, Tlymphocytes, fibroblasts, endothelial cells, and keratinocytes by an inflammatory stimulus. IL-8 is a member of the beta-thromboglobulin superfamily and structurally related to platelet factor 4. [NIH] Intermittent: Occurring at separated intervals; having periods of cessation of activity. [EU] Internal Medicine: A medical specialty concerned with the diagnosis and treatment of
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diseases of the internal organ systems of adults. [NIH] Internal radiation: A procedure in which radioactive material sealed in needles, seeds, wires, or catheters is placed directly into or near the tumor. Also called brachytherapy, implant radiation, or interstitial radiation therapy. [NIH] Interstitial: Pertaining to or situated between parts or in the interspaces of a tissue. [EU] Interstitial Collagenase: A member of the metalloproteinase family of enzymes that is principally responsible for cleaving fibrillar collagen. It can degrade interstitial collagens, types I, II and III. EC 3.4.24.7. [NIH] Intervertebral: Situated between two contiguous vertebrae. [EU] Intestinal: Having to do with the intestines. [NIH] Intestines: The section of the alimentary canal from the stomach to the anus. It includes the large intestine and small intestine. [NIH] Intracellular: Inside a cell. [NIH] Intrahepatic: Within the liver. [NIH] Intramuscular: IM. Within or into muscle. [NIH] Intraocular: Within the eye. [EU] Intraocular pressure: Pressure of the fluid inside the eye; normal IOP varies among individuals. [NIH] Intravascular: Within a vessel or vessels. [EU] Intravenous: IV. Into a vein. [NIH] Intravesical: Within the bladder. [NIH] Intrinsic: Situated entirely within or pertaining exclusively to a part. [EU] Inulin: A starch found in the tubers and roots of many plants. Since it is hydrolyzable to fructose, it is classified as a fructosan. It has been used in physiologic investigation for determination of the rate of glomerular function. [NIH] Invasive: 1. Having the quality of invasiveness. 2. Involving puncture or incision of the skin or insertion of an instrument or foreign material into the body; said of diagnostic techniques. [EU]
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] Ion Exchange: Reversible chemical reaction between a solid, often an ION exchange resin, and a fluid whereby ions may be exchanged from one substance to another. This technique is used in water purification, in research, and in industry. [NIH] Ions: An atom or group of atoms that have a positive or negative electric charge due to a gain (negative charge) or loss (positive charge) of one or more electrons. Atoms with a positive charge are known as cations; those with a negative charge are anions. [NIH] Iris: The most anterior portion of the uveal layer, separating the anterior chamber from the posterior. It consists of two layers - the stroma and the pigmented epithelium. Color of the iris depends on the amount of melanin in the stroma on reflection from the pigmented epithelium. [NIH] Irradiation: The use of high-energy radiation from x-rays, neutrons, and other sources to kill
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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] Irritants: Drugs that act locally on cutaneous or mucosal surfaces to produce inflammation; those that cause redness due to hyperemia are rubefacients; those that raise blisters are vesicants and those that penetrate sebaceous glands and cause abscesses are pustulants; tear gases and mustard gases are also irritants. [NIH] Ischemia: Deficiency of blood in a part, due to functional constriction or actual obstruction of a blood vessel. [EU] Islet: Cell producing insulin in pancreas. [NIH] Joint: The point of contact between elements of an animal skeleton with the parts that surround and support it. [NIH] Joint Capsule: The sac enclosing a joint. It is composed of an outer fibrous articular capsule and an inner synovial membrane. [NIH] Karaya Gum: Polysaccharide gum from Sterculia urens, an Indian tree; it is used as suspending or stabilizing agent in foods, cosmetics and pharmaceuticals; also as bulkforming laxative, surgical lubricant and adhesive, and in the treatment of skin ulcers. [NIH] Kb: A measure of the length of DNA fragments, 1 Kb = 1000 base pairs. The largest DNA fragments are up to 50 kilobases long. [NIH] Keratan Sulfate: A sulfated mucopolysaccharide initially isolated from bovine cornea. At least two types are known. Type I, found mostly in the cornea, contains D-galactose and Dglucosamine-6-O-sulfate as the repeating unit; type II, found in skeletal tissues, contains Dgalactose and D-galactosamine-6-O-sulfate as the repeating unit. [NIH] Keratin: A class of fibrous proteins or scleroproteins important both as structural proteins and as keys to the study of protein conformation. The family represents the principal constituent of epidermis, hair, nails, horny tissues, and the organic matrix of tooth enamel. Two major conformational groups have been characterized, alpha-keratin, whose peptide backbone forms an alpha-helix, and beta-keratin, whose backbone forms a zigzag or pleated sheet structure. [NIH] Keratinocytes: Epidermal cells which synthesize keratin and undergo characteristic changes as they move upward from the basal layers of the epidermis to the cornified (horny) layer of the skin. Successive stages of differentiation of the keratinocytes forming the epidermal layers are basal cell, spinous or prickle cell, and the granular cell. [NIH] Keto: It consists of 8 carbon atoms and within the endotoxins, it connects poysaccharide and lipid A. [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] 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.
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Chemically unstable. [EU] Laminin: Large, noncollagenous glycoprotein with antigenic properties. It is localized in the basement membrane lamina lucida and functions to bind epithelial cells to the basement membrane. Evidence suggests that the protein plays a role in tumor invasion. [NIH] Large Intestine: The part of the intestine that goes from the cecum to the rectum. The large intestine absorbs water from stool and changes it from a liquid to a solid form. The large intestine is 5 feet long and includes the appendix, cecum, colon, and rectum. Also called colon. [NIH] Larynx: An irregularly shaped, musculocartilaginous tubular structure, lined with mucous membrane, located at the top of the trachea and below the root of the tongue and the hyoid bone. It is the essential sphincter guarding the entrance into the trachea and functioning secondarily as the organ of voice. [NIH] Latent: Phoria which occurs at one distance or another and which usually has no troublesome effect. [NIH] Laxative: An agent that acts to promote evacuation of the bowel; a cathartic or purgative. [EU]
Lectin: A complex molecule that has both protein and sugars. Lectins are able to bind to the outside of a cell and cause biochemical changes in it. Lectins are made by both animals and plants. [NIH] Lens: The transparent, double convex (outward curve on both sides) structure suspended between the aqueous and vitreous; helps to focus light on the retina. [NIH] Lesion: An area of abnormal tissue change. [NIH] Lethal: Deadly, fatal. [EU] Leucine: An essential branched-chain amino acid important for hemoglobin formation. [NIH] Leukemia: Cancer of blood-forming tissue. [NIH] Leukocyte Elastase: An enzyme that catalyzes the hydrolysis of proteins, including elastin. It cleaves preferentially bonds at the carboxyl side of Ala and Val, with greater specificity for Ala. EC 3.4.21.37. [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] Libido: The psychic drive or energy associated with sexual instinct in the broad sense (pleasure and love-object seeking). It may also connote the psychic energy associated with instincts in general that motivate behavior. [NIH] Library Services: Services offered to the library user. They include reference and circulation. [NIH]
Lidocaine: A local anesthetic and cardiac depressant used as an antiarrhythmia agent. Its actions are more intense and its effects more prolonged than those of procaine but its duration of action is shorter than that of bupivacaine or prilocaine. [NIH] Ligament: A band of fibrous tissue that connects bones or cartilages, serving to support and strengthen joints. [EU]
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Ligands: A RNA simulation method developed by the MIT. [NIH] Linkage: The tendency of two or more genes in the same chromosome to remain together from one generation to the next more frequently than expected according to the law of independent assortment. [NIH] Lipid: Fat. [NIH] 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] Liposomes: Artificial, single or multilaminar vesicles (made from lecithins or other lipids) that are used for the delivery of a variety of biological molecules or molecular complexes to cells, for example, drug delivery and gene transfer. They are also used to study membranes and membrane proteins. [NIH] 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] 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] Loop: A wire usually of platinum bent at one end into a small loop (usually 4 mm inside diameter) and used in transferring microorganisms. [NIH] Low-density lipoprotein: Lipoprotein that contains most of the cholesterol in the blood. LDL carries cholesterol to the tissues of the body, including the arteries. A high level of LDL increases the risk of heart disease. LDL typically contains 60 to 70 percent of the total serum cholesterol and both are directly correlated with CHD risk. [NIH] Lucida: An instrument, invented by Wollaton, consisting essentially of a prism or a mirror through which an object can be viewed so as to appear on a plane surface seen in direct view and on which the outline of the object may be traced. [NIH] Lumbar: Pertaining to the loins, the part of the back between the thorax and the pelvis. [EU] Lumen: The cavity or channel within a tube or tubular organ. [EU] Lupus: A form of cutaneous tuberculosis. It is seen predominantly in women and typically involves the nasal, buccal, and conjunctival mucosa. [NIH] Lyases: A class of enzymes that catalyze the cleavage of C-C, C-O, and C-N, and other bonds by other means than by hydrolysis or oxidation. (Enzyme Nomenclature, 1992) EC 4. [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
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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] 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] Lysine: An essential amino acid. It is often added to animal feed. [NIH] Macroglia: A type of neuroglia composed of astrocytes. [NIH] Macrophage: A type of white blood cell that surrounds and kills microorganisms, removes dead cells, and stimulates the action of other immune system cells. [NIH] 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] Malaise: A vague feeling of bodily discomfort. [EU] Malaria: A protozoan disease caused in humans by four species of the genus Plasmodium (P. falciparum (malaria, falciparum), P. vivax (malaria, vivax), P. ovale, and P. malariae) and transmitted by the bite of an infected female mosquito of the genus Anopheles. Malaria is endemic in parts of Asia, Africa, Central and South America, Oceania, and certain Caribbean islands. It is characterized by extreme exhaustion associated with paroxysms of high fever, sweating, shaking chills, and anemia. Malaria in animals is caused by other species of plasmodia. [NIH] Malaria, Falciparum: Malaria caused by Plasmodium falciparum. This is the severest form of malaria and is associated with the highest levels of parasites in the blood. This disease is characterized by irregularly recurring febrile paroxysms that in extreme cases occur with acute cerebral, renal, or gastrointestinal manifestations. [NIH] Malaria, Vivax: Malaria caused by Plasmodium vivax. This form of malaria is less severe than malaria, falciparum, but there is a higher probability for relapses to occur. Febrile paroxysms often occur every other day. [NIH] Malignant: Cancerous; a growth with a tendency to invade and destroy nearby tissue and spread to other parts of the body. [NIH] Malignant tumor: A tumor capable of metastasizing. [NIH] Malnutrition: A condition caused by not eating enough food or not eating a balanced diet. [NIH]
Mammary: Pertaining to the mamma, or breast. [EU] Mammogram: An x-ray of the breast. [NIH] Mandible: The largest and strongest bone of the face constituting the lower jaw. It supports
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the lower teeth. [NIH] Manifest: Being the part or aspect of a phenomenon that is directly observable : concretely expressed in behaviour. [EU] Matrix metalloproteinase: A member of a group of enzymes that can break down proteins, such as collagen, that are normally found in the spaces between cells in tissues (i.e., extracellular matrix proteins). Because these enzymes need zinc or calcium atoms to work properly, they are called metalloproteinases. Matrix metalloproteinases are involved in wound healing, angiogenesis, and tumor cell metastasis. [NIH] Meatus: A canal running from the internal auditory foramen through the petrous portion of the temporal bone. It gives passage to the facial and auditory nerves together with the auditory branch of the basilar artery and the internal auditory veins. [NIH] Medial: Lying near the midsaggital plane of the body; opposed to lateral. [NIH] Mediate: Indirect; accomplished by the aid of an intervening medium. [EU] Mediator: An object or substance by which something is mediated, such as (1) a structure of the nervous system that transmits impulses eliciting a specific response; (2) a chemical substance (transmitter substance) that induces activity in an excitable tissue, such as nerve or muscle; or (3) a substance released from cells as the result of the interaction of antigen with antibody or by the action of antigen with a sensitized lymphocyte. [EU] Medical Staff: Professional medical personnel who provide care to patients in an organized facility, institution or agency. [NIH] Medicament: A medicinal substance or agent. [EU] MEDLINE: An online database of MEDLARS, the computerized bibliographic Medical Literature Analysis and Retrieval System of the National Library of Medicine. [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] Membrane: A very thin layer of tissue that covers a surface. [NIH] Membrane Proteins: Proteins which are found in membranes including cellular and intracellular membranes. They consist of two types, peripheral and integral proteins. They include most membrane-associated enzymes, antigenic proteins, transport proteins, and drug, hormone, and lectin receptors. [NIH] 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]
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Mental Disorders: Psychiatric illness or diseases manifested by breakdowns in the adaptational process expressed primarily as abnormalities of thought, feeling, and behavior producing either distress or impairment of function. [NIH] Mental Health: The state wherein the person is well adjusted. [NIH] Mental Processes: Conceptual functions or thinking in all its forms. [NIH] Mental Retardation: Refers to sub-average general intellectual functioning which originated during the developmental period and is associated with impairment in adaptive behavior. [NIH]
Menthol: An alcohol produced from mint oils or prepared synthetically. [NIH] Mesenchymal: Refers to cells that develop into connective tissue, blood vessels, and lymphatic tissue. [NIH] Mesentery: A layer of the peritoneum which attaches the abdominal viscera to the abdominal wall and conveys their blood vessels and nerves. [NIH] Mesoderm: The middle germ layer of the embryo. [NIH] Mesothelial: It lines the peritonealla and pleural cavities. [NIH] Meta-Analysis: A quantitative method of combining the results of independent studies (usually drawn from the published literature) and synthesizing summaries and conclusions which may be used to evaluate therapeutic effectiveness, plan new studies, etc., with application chiefly in the areas of research and medicine. [NIH] Metabolic disorder: A condition in which normal metabolic processes are disrupted, usually because of a missing enzyme. [NIH] Metabolite: Any substance produced by metabolism or by a metabolic process. [EU] 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] Methionine: A sulfur containing essential amino acid that is important in many body functions. It is a chelating agent for heavy metals. [NIH] Methylene Blue: A compound consisting of dark green crystals or crystalline powder, having a bronze-like luster. Solutions in water or alcohol have a deep blue color. Methylene blue is used as a bacteriologic stain and as an indicator. It inhibits Guanylate cyclase, and has been used to treat cyanide poisoning and to lower levels of methemoglobin. [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] Microcalcifications: Tiny deposits of calcium in the breast that cannot be felt but can be detected on a mammogram. A cluster of these very small specks of calcium may indicate that cancer is present. [NIH] Microfibrils: Components of the extracellular matrix consisting primarily of fibrillin. They are essential for the integrity of elastic fibers. [NIH]
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Microfilaments: The smallest of the cytoskeletal filaments. They are composed chiefly of actin. [NIH] Microorganism: An organism that can be seen only through a microscope. Microorganisms include bacteria, protozoa, algae, and fungi. Although viruses are not considered living organisms, they are sometimes classified as microorganisms. [NIH] Microscopy: The application of microscope magnification to the study of materials that cannot be properly seen by the unaided eye. [NIH] Microspheres: Small uniformly-sized spherical particles frequently radioisotopes or various reagents acting as tags or markers. [NIH]
labeled
with
Microtubules: Slender, cylindrical filaments found in the cytoskeleton of plant and animal cells. They are composed of the protein tubulin. [NIH] Migration: The systematic movement of genes between populations of the same species, geographic race, or variety. [NIH] Mineralization: The action of mineralizing; the state of being mineralized. [EU] Miotic: 1. Pertaining to, characterized by, or producing miosis : contraction of the pupil. 2. An agent that causes the pupil to contract. 3. Meiotic: characterized by cell division. [EU] Mitochondria: Parts of a cell where aerobic production (also known as cell respiration) takes place. [NIH] Mitosis: A method of indirect cell division by means of which the two daughter nuclei normally receive identical complements of the number of chromosomes of the somatic cells of the species. [NIH] Mobility: Capability of movement, of being moved, or of flowing freely. [EU] Mobilization: The process of making a fixed part or stored substance mobile, as by separating a part from surrounding structures to make it accessible for an operative procedure or by causing release into the circulation for body use of a substance stored in the body. [EU] Modeling: A treatment procedure whereby the therapist presents the target behavior which the learner is to imitate and make part of his repertoire. [NIH] Models, Chemical: Theoretical representations that simulate the behavior or activity of chemical processes or phenomena; includes the use of mathematical equations, computers, and other electronic equipment. [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 Chaperones: A family of cellular proteins that mediate the correct assembly or disassembly of other polypeptides, and in some cases their assembly into oligomeric structures, but which are not components of those final structures. It is believed that chaperone proteins assist polypeptides to self-assemble by inhibiting alternative assembly pathways that produce nonfunctional structures. Some classes of molecular chaperones are the nucleoplasmins, the chaperonins, the heat-shock proteins 70, and the heat-shock proteins 90. [NIH] 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
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and one atom of oxygen, is 18 (i.e., 2 + 16). [NIH] Molecular Probes: A group of atoms or molecules attached to other molecules or cellular structures and used in studying the properties of these molecules and structures. Radioactive DNA or RNA sequences are used in molecular genetics to detect the presence of a complementary sequence by molecular hybridization. [NIH] 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 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] Monosomy: The condition in which one chromosome of a pair is missing. In a normally diploid cell it is represented symbolically as 2N-1. [NIH] Monotherapy: A therapy which uses only one drug. [EU] Morphine: The principal alkaloid in opium and the prototype opiate analgesic and narcotic. Morphine has widespread effects in the central nervous system and on smooth muscle. [NIH] Morphogenesis: The development of the form of an organ, part of the body, or organism. [NIH]
Morphological: Relating to the configuration or the structure of live organs. [NIH] Morphology: The science of the form and structure of organisms (plants, animals, and other forms of life). [NIH] Motility: The ability to move spontaneously. [EU] Motor nerve: An efferent nerve conveying an impulse that excites muscular contraction. [NIH]
Motor Neurons: Neurons which activate muscle cells. [NIH] Mucinous: Containing or resembling mucin, the main compound in mucus. [NIH] Mucins: A secretion containing mucopolysaccharides and protein that is the chief constituent of mucus. [NIH] Mucosa: A mucous membrane, or tunica mucosa. [EU] Mucosal Lining: The lining of GI tract organs that makes mucus. [NIH] Mucositis: A complication of some cancer therapies in which the lining of the digestive system becomes inflamed. Often seen as sores in the mouth. [NIH] Mucus: The viscous secretion of mucous membranes. It contains mucin, white blood cells, water, inorganic salts, and exfoliated cells. [NIH]
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Multiple sclerosis: A disorder of the central nervous system marked by weakness, numbness, a loss of muscle coordination, and problems with vision, speech, and bladder control. Multiple sclerosis is thought to be an autoimmune disease in which the body's immune system destroys myelin. Myelin is a substance that contains both protein and fat (lipid) and serves as a nerve insulator and helps in the transmission of nerve signals. [NIH] Muscle Contraction: A process leading to shortening and/or development of tension in muscle tissue. Muscle contraction occurs by a sliding filament mechanism whereby actin filaments slide inward among the myosin filaments. [NIH] Muscle Fibers: Large single cells, either cylindrical or prismatic in shape, that form the basic unit of muscle tissue. They consist of a soft contractile substance enclosed in a tubular sheath. [NIH] Muscle relaxant: An agent that specifically aids in reducing muscle tension, as those acting at the polysynaptic neurons of motor nerves (e.g. meprobamate) or at the myoneural junction (curare and related compounds). [EU] Muscle tension: A force in a material tending to produce extension; the state of being stretched. [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] Mustard Gas: Severe irritant and vesicant of skin, eyes, and lungs. It may cause blindness and lethal lung edema and was formerly used as a war gas. The substance has been proposed as a cytostatic and for treatment of psoriasis. It has been listed as a known carcinogen in the Fourth Annual Report on Carcinogens (NTP-85-002, 1985) (Merck, 11th ed). [NIH] Mutagenesis: Process of generating genetic mutations. It may occur spontaneously or be induced by mutagens. [NIH] Mutagens: Chemical agents that increase the rate of genetic mutation by interfering with the function of nucleic acids. A clastogen is a specific mutagen that causes breaks in chromosomes. [NIH] Myalgia: Pain in a muscle or muscles. [EU] Myelin: The fatty substance that covers and protects nerves. [NIH] Myocardium: The muscle tissue of the heart composed of striated, involuntary muscle known as cardiac muscle. [NIH] Myopathy: Any disease of a muscle. [EU] Myopia: That error of refraction in which rays of light entering the eye parallel to the optic axis are brought to a focus in front of the retina, as a result of the eyeball being too long from front to back (axial m.) or of an increased strength in refractive power of the media of the eye (index m.). Called also nearsightedness, because the near point is less distant than it is in emmetropia with an equal amplitude of accommodation. [EU] 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]
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Narcosis: A general and nonspecific reversible depression of neuronal excitability, produced by a number of physical and chemical aspects, usually resulting in stupor. [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] Nausea: An unpleasant sensation in the stomach usually accompanied by the urge to vomit. Common causes are early pregnancy, sea and motion sickness, emotional stress, intense pain, food poisoning, and various enteroviruses. [NIH] NCI: National Cancer Institute. NCI, part of the National Institutes of Health of the United States Department of Health and Human Services, is the federal government's principal agency for cancer research. NCI conducts, coordinates, and funds cancer research, training, health information dissemination, and other programs with respect to the cause, diagnosis, prevention, and treatment of cancer. Access the NCI Web site at http://cancer.gov. [NIH] Necrosis: A pathological process caused by the progressive degradative action of enzymes that is generally associated with severe cellular trauma. It is characterized by mitochondrial swelling, nuclear flocculation, uncontrolled cell lysis, and ultimately cell death. [NIH] Need: A state of tension or dissatisfaction felt by an individual that impels him to action toward a goal he believes will satisfy the impulse. [NIH] Neocortex: The largest portion of the cerebral cortex. It is composed of neurons arranged in six layers. [NIH] 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] Neoplastic meningitis: Tumor cells that have spread from the original (primary) tumor to the tissue that covers the brain, spinal cord, or both. [NIH] Nephritis: Inflammation of the kidney; a focal or diffuse proliferative or destructive process which may involve the glomerulus, tubule, or interstitial renal tissue. [EU] Nephrolithiasis: Kidney stones. [NIH] Nephropathy: Disease of the kidneys. [EU] Nerve: A cordlike structure of nervous tissue that connects parts of the nervous system with other tissues of the body and conveys nervous impulses to, or away from, these tissues. [NIH] Nerve Degeneration: Loss of functional activity and trophic degeneration of nerve axons and their terminal arborizations following the destruction of their cells of origin or interruption of their continuity with these cells. The pathology is characteristic of neurodegenerative diseases. Often the process of nerve degeneration is studied in research on neuroanatomical localization and correlation of the neurophysiology of neural pathways. [NIH]
Nerve Endings: Specialized terminations of peripheral neurons. Nerve endings include neuroeffector junction(s) by which neurons activate target organs and sensory receptors which transduce information from the various sensory modalities and send it centrally in the nervous system. Presynaptic nerve endings are presynaptic terminals. [NIH]
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Nerve Fibers: Slender processes of neurons, especially the prolonged axons that conduct nerve impulses. [NIH] Nerve Growth Factor: Nerve growth factor is the first of a series of neurotrophic factors that were found to influence the growth and differentiation of sympathetic and sensory neurons. It is comprised of alpha, beta, and gamma subunits. The beta subunit is responsible for its growth stimulating activity. [NIH] Nervous System: The entire nerve apparatus composed of the brain, spinal cord, nerves and ganglia. [NIH] Neural: 1. Pertaining to a nerve or to the nerves. 2. Situated in the region of the spinal axis, as the neutral arch. [EU] Neural Crest: A strip of specialized ectoderm flanking each side of the embryonal neural plate, which after the closure of the neural tube, forms a column of isolated cells along the dorsal aspect of the neural tube. Most of the cranial and all of the spinal sensory ganglion cells arise by differentiation of neural crest cells. [NIH] Neural Pathways: Neural tracts connecting one part of the nervous system with another. [NIH]
Neuralgia: Intense or aching pain that occurs along the course or distribution of a peripheral or cranial nerve. [NIH] Neurites: In tissue culture, hairlike projections of neurons stimulated by growth factors and other molecules. These projections may go on to form a branched tree of dendrites or a single axon or they may be reabsorbed at a later stage of development. "Neurite" may refer to any filamentous or pointed outgrowth of an embryonal or tissue-culture neural cell. [NIH] Neuritis: A general term indicating inflammation of a peripheral or cranial nerve. Clinical manifestation may include pain; paresthesias; paresis; or hypesthesia. [NIH] Neuroblastoma: Cancer that arises in immature nerve cells and affects mostly infants and children. [NIH] Neurogenic: Loss of bladder control caused by damage to the nerves controlling the bladder. [NIH] Neuroglia: The non-neuronal cells of the nervous system. They are divided into macroglia (astrocytes, oligodendroglia, and schwann cells) and microglia. They not only provide physical support, but also respond to injury, regulate the ionic and chemical composition of the extracellular milieu, participate in the blood-brain and blood-retina barriers, form the myelin insulation of nervous pathways, guide neuronal migration during development, and exchange metabolites with neurons. Neuroglia have high-affinity transmitter uptake systems, voltage-dependent and transmitter-gated ion channels, and can release transmitters, but their role in signaling (as in many other functions) is unclear. [NIH] Neuroma: A tumor that arises in nerve cells. [NIH] Neuronal: Pertaining to a neuron or neurons (= conducting cells of the nervous system). [EU] Neuronal Plasticity: The capacity of the nervous system to change its reactivity as the result of successive activations. [NIH] Neurons: The basic cellular units of nervous tissue. Each neuron consists of a body, an axon, 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] Neurophysiology: The scientific discipline concerned with the physiology of the nervous
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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] Neurotrophins: A nerve growth factor. [NIH] Neutralization: An act or process of neutralizing. [EU] Neutrons: Electrically neutral elementary particles found in all atomic nuclei except light hydrogen; the mass is equal to that of the proton and electron combined and they are unstable when isolated from the nucleus, undergoing beta decay. Slow, thermal, epithermal, and fast neutrons refer to the energy levels with which the neutrons are ejected from heavier nuclei during their decay. [NIH] Neutrophil: A type of white blood cell. [NIH] Nevirapine: A potent, non-nucleoside reverse transcriptase inhibitor used in combination with nucleoside analogues for treatment of HIV infection and AIDS. [NIH] Nickel: A trace element with the atomic symbol Ni, atomic number 28, and atomic weight 58.69. It is a cofactor of the enzyme urease. [NIH] Nifedipine: A potent vasodilator agent with calcium antagonistic action. It is a useful antianginal agent that also lowers blood pressure. The use of nifedipine as a tocolytic is being investigated. [NIH] Nitric Oxide: A free radical gas produced endogenously by a variety of mammalian cells. It is synthesized from arginine by a complex reaction, catalyzed by nitric oxide synthase. Nitric oxide is endothelium-derived relaxing factor. It is released by the vascular endothelium and mediates the relaxation induced by some vasodilators such as acetylcholine and bradykinin. It also inhibits platelet aggregation, induces disaggregation of aggregated platelets, and inhibits platelet adhesion to the vascular endothelium. Nitric oxide activates cytosolic guanylate cyclase and thus elevates intracellular levels of cyclic GMP. [NIH]
Nitrogen: An element with the atomic symbol N, atomic number 7, and atomic weight 14. Nitrogen exists as a diatomic gas and makes up about 78% of the earth's atmosphere by volume. It is a constituent of proteins and nucleic acids and found in all living cells. [NIH] Non-nucleoside: A member of a class of compounds, including delavirdine, loviride and nevirapine, that acts to directly combine with and block the action of HIV's reverse transcriptase. [NIH] Norepinephrine: Precursor of epinephrine that is secreted by the adrenal medulla and is a widespread central and autonomic neurotransmitter. Norepinephrine is the principal transmitter of most postganglionic sympathetic fibers and of the diffuse projection system in the brain arising from the locus ceruleus. It is also found in plants and is used pharmacologically as a sympathomimetic. [NIH] Nuclear: A test of the structure, blood flow, and function of the kidneys. The doctor injects a mildly radioactive solution into an arm vein and uses x-rays to monitor its progress through the kidneys. [NIH] Nuclear Localization Signal: Short, predominantly basic amino acid sequences identified as nuclear import signals for some proteins. These sequences are believed to interact with specific receptors at nuclear pores. [NIH]
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Nuclear Pore: An opening through the nuclear envelope formed by the nuclear pore complex which transports nuclear proteins or RNA into or out of the cell nucleus and which, under some conditions, acts as an ion channel. [NIH] 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] Nucleolus: A small dense body (sub organelle) within the nucleus of eukaryotic cells, visible by phase contrast and interference microscopy in live cells throughout interphase. Contains RNA and protein and is the site of synthesis of ribosomal RNA. [NIH] Nucleus: A body of specialized protoplasm found in nearly all cells and containing the chromosomes. [NIH] Nursing Care: Care given to patients by nursing service personnel. [NIH] Nutritive Value: An indication of the contribution of a food to the nutrient content of the diet. This value depends on the quantity of a food which is digested and absorbed and the amounts of the essential nutrients (protein, fat, carbohydrate, minerals, vitamins) which it contains. This value can be affected by soil and growing conditions, handling and storage, and processing. [NIH] Occipital Lobe: Posterior part of the cerebral hemisphere. [NIH] Ocular: 1. Of, pertaining to, or affecting the eye. 2. Eyepiece. [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] Olfactory Bulb: Ovoid body resting on the cribriform plate of the ethmoid bone where the olfactory nerve terminates. The olfactory bulb contains several types of nerve cells including the mitral cells, on whose dendrites the olfactory nerve synapses, forming the olfactory glomeruli. The accessory olfactory bulb, which receives the projection from the vomeronasal organ via the vomeronasal nerve, is also included here. [NIH] Oligonucleotide Probes: Synthetic or natural oligonucleotides used in hybridization studies in order to identify and study specific nucleic acid fragments, e.g., DNA segments near or within a specific gene locus or gene. The probe hybridizes with a specific mRNA, if present. Conventional techniques used for testing for the hybridization product include dot blot assays, Southern blot assays, and DNA:RNA hybrid-specific antibody tests. Conventional labels for the probe include the radioisotope labels 32P and 125I and the chemical label biotin. [NIH] Oligopeptides: Peptides composed of between two and twelve amino acids. [NIH] Oligosaccharides: Carbohydrates consisting of between two and ten monosaccharides connected by either an alpha- or beta-glycosidic link. They are found throughout nature in both the free and bound form. [NIH] Omega-3 fatty acid: A type of fat obtained in the diet and involved in immunity. [NIH] Oncogene: A gene that normally directs cell growth. If altered, an oncogene can promote or
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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] On-line: A sexually-reproducing population derived from a common parentage. [NIH] Opacity: Degree of density (area most dense taken for reading). [NIH] Ophthalmic: Pertaining to the eye. [EU] Opioid Peptides: The endogenous peptides with opiate-like activity. The three major classes currently recognized are the enkephalins, the dynorphins, and the endorphins. Each of these families derives from different precursors, proenkephalin, prodynorphin, and proopiomelanocortin, respectively. There are also at least three classes of opioid receptors, but the peptide families do not map to the receptors in a simple way. [NIH] Opsin: A protein formed, together with retinene, by the chemical breakdown of metarhodopsin. [NIH] Optic Nerve: The 2nd cranial nerve. The optic nerve conveys visual information from the retina to the brain. The nerve carries the axons of the retinal ganglion cells which sort at the optic chiasm and continue via the optic tracts to the brain. The largest projection is to the lateral geniculate nuclei; other important targets include the superior colliculi and the suprachiasmatic nuclei. Though known as the second cranial nerve, it is considered part of the central nervous system. [NIH] Orderly: A male hospital attendant. [NIH] 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, or a fluid substitute that mimics the natural state within the organism). [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] Ornithine: An amino acid produced in the urea cycle by the splitting off of urea from arginine. [NIH] Osmosis: Tendency of fluids (e.g., water) to move from the less concentrated to the more concentrated side of a semipermeable membrane. [NIH] Osmotic: Pertaining to or of the nature of osmosis (= the passage of pure solvent from a solution of lesser to one of greater solute concentration when the two solutions are separated by a membrane which selectively prevents the passage of solute molecules, but is permeable to the solvent). [EU] Ossification: The formation of bone or of a bony substance; the conversion of fibrous tissue or of cartilage into bone or a bony substance. [EU] Osteoarthritis: A progressive, degenerative joint disease, the most common form of arthritis, especially in older persons. The disease is thought to result not from the aging process but from biochemical changes and biomechanical stresses affecting articular cartilage. In the foreign literature it is often called osteoarthrosis deformans. [NIH] Osteoclasts: A large multinuclear cell associated with the absorption and removal of bone. An odontoclast, also called cementoclast, is cytomorphologically the same as an osteoclast and is involved in cementum resorption. [NIH]
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Osteogenesis: The histogenesis of bone including ossification. It occurs continuously but particularly in the embryo and child and during fracture repair. [NIH] Osteomalacia: A condition marked by softening of the bones (due to impaired mineralization, with excess accumulation of osteoid), with pain, tenderness, muscular weakness, anorexia, and loss of weight, resulting from deficiency of vitamin D and calcium. [EU]
Osteopetrosis: Excessive formation of dense trabecular bone leading to pathological fractures, osteitis, splenomegaly with infarct, anemia, and extramedullary hemopoiesis. [NIH]
Osteoporosis: Reduction of bone mass without alteration in the composition of bone, leading to fractures. Primary osteoporosis can be of two major types: postmenopausal osteoporosis and age-related (or senile) osteoporosis. [NIH] Osteotomy: The surgical cutting of a bone. [EU] Otitis: Inflammation of the ear, which may be marked by pain, fever, abnormalities of hearing, hearing loss, tinnitus, and vertigo. [EU] Overexpress: An excess of a particular protein on the surface of a cell. [NIH] Ovulation: The discharge of a secondary oocyte from a ruptured graafian follicle. [NIH] Oxidation: The act of oxidizing or state of being oxidized. Chemically it consists in the increase of positive charges on an atom or the loss of negative charges. Most biological oxidations are accomplished by the removal of a pair of hydrogen atoms (dehydrogenation) from a molecule. Such oxidations must be accompanied by reduction of an acceptor molecule. Univalent o. indicates loss of one electron; divalent o., the loss of two electrons. [EU]
Oxidative metabolism: A chemical process in which oxygen is used to make energy from carbohydrates (sugars). Also known as aerobic respiration, cell respiration, or aerobic metabolism. [NIH] Oxygenation: The process of supplying, treating, or mixing with oxygen. No:1245 oxygenation the process of supplying, treating, or mixing with oxygen. [EU] Oxygenator: An apparatus by which oxygen is introduced into the blood during circulation outside the body, as during open heart surgery. [NIH] Pachymeningitis: Inflammation of the dura mater of the brain, the spinal cord or the optic nerve. [NIH] Palliative: 1. Affording relief, but not cure. 2. An alleviating medicine. [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] 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] Parenteral: Not through the alimentary canal but rather by injection through some other route, as subcutaneous, intramuscular, intraorbital, intracapsular, intraspinal, intrasternal, intravenous, etc. [EU]
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Parenteral Nutrition: The administering of nutrients for assimilation and utilization by a patient who cannot maintain adequate nutrition by enteral feeding alone. Nutrients are administered by a route other than the alimentary canal (e.g., intravenously, subcutaneously). [NIH] Paresis: A general term referring to a mild to moderate degree of muscular weakness, occasionally used as a synonym for paralysis (severe or complete loss of motor function). In the older literature, paresis often referred specifically to paretic neurosyphilis. "General paresis" and "general paralysis" may still carry that connotation. Bilateral lower extremity paresis is referred to as paraparesis. [NIH] Paresthesias: Abnormal touch sensations, such as burning or prickling, that occur without an outside stimulus. [NIH] Parietal: 1. Of or pertaining to the walls of a cavity. 2. Pertaining to or located near the parietal bone, as the parietal lobe. [EU] Parity: The number of offspring a female has borne. It is contrasted with gravidity, which refers to the number of pregnancies, regardless of outcome. [NIH] Paroxysmal: Recurring in paroxysms (= spasms or seizures). [EU] 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] Patient Compliance: Voluntary cooperation of the patient in following a prescribed regimen. [NIH] Patient Education: The teaching or training of patients concerning their own health needs. [NIH]
Pelvic: Pertaining to the pelvis. [EU] Pentosan polysulfate: A drug used to relieve pain or discomfort associated with chronic inflammation of the bladder. It is also being evaluated for its protective effects on the gastrointestinal tract in people undergoing radiation therapy. [NIH] Pepsin: An enzyme made in the stomach that breaks down proteins. [NIH] Pepsin A: Formed from pig pepsinogen by cleavage of one peptide bond. The enzyme is a single polypeptide chain and is inhibited by methyl 2-diaazoacetamidohexanoate. It cleaves peptides preferentially at the carbonyl linkages of phenylalanine or leucine and acts as the principal digestive enzyme of gastric juice. [NIH] Peptide: Any compound consisting of two or more amino acids, the building blocks of proteins. Peptides are combined to make proteins. [NIH] Peptide Fragments: Partial proteins formed by partial hydrolysis of complete proteins. [NIH] Peptide T: N-(N-(N(2)-(N-(N-(N-(N-D-Alanyl L-seryl)-L-threonyl)-L-threonyl) L-threonyl)-
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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] Perception: The ability quickly and accurately to recognize similarities and differences among presented objects, whether these be pairs of words, pairs of number series, or multiple sets of these or other symbols such as geometric figures. [NIH] Percutaneous: Performed through the skin, as injection of radiopacque material in radiological examination, or the removal of tissue for biopsy accomplished by a needle. [EU] Perennial: Lasting through the year of for several years. [EU] Pericarditis: Inflammation of the pericardium. [EU] Pericardium: The fibroserous sac surrounding the heart and the roots of the great vessels. [NIH]
Perineal: Pertaining to the perineum. [EU] 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 Neuropathy: Nerve damage, usually affecting the feet and legs; causing pain, numbness, or a tingling feeling. Also called "somatic neuropathy" or "distal sensory polyneuropathy." [NIH] Peritoneal: Having to do with the peritoneum (the tissue that lines the abdominal wall and covers most of the organs in the abdomen). [NIH] Peritoneal Cavity: The space enclosed by the peritoneum. It is divided into two portions, the greater sac and the lesser sac or omental bursa, which lies behind the stomach. The two sacs are connected by the foramen of Winslow, or epiploic foramen. [NIH] Peritoneal Dialysis: Dialysis fluid being introduced into and removed from the peritoneal cavity as either a continuous or an intermittent procedure. [NIH] Peritoneum: Endothelial lining of the abdominal cavity, the parietal peritoneum covering the inside of the abdominal wall and the visceral peritoneum covering the bowel, the mesentery, and certain of the organs. The portion that covers the bowel becomes the serosal layer of the bowel wall. [NIH] 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] Pesticides: Chemicals used to destroy pests of any sort. The concept includes fungicides (industrial fungicides), insecticides, rodenticides, etc. [NIH] Pharmaceutic Aids: Substances which are of little or no therapeutic value, but are necessary in the manufacture, compounding, storage, etc., of pharmaceutical preparations or drug dosage forms. They include solvents, diluting agents, and suspending agents, and emulsifying agents. Also, antioxidants; preservatives, pharmaceutical; dyes (coloring agents); flavoring agents; vehicles; excipients; ointment bases. [NIH] Pharmaceutical Preparations: Drugs intended for human or veterinary use, presented in their finished dosage form. Included here are materials used in the preparation and/or
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formulation of the finished dosage form. [NIH] Pharmaceutical Solutions: Homogeneous liquid preparations that contain one or more chemical substances dissolved, i.e., molecularly dispersed, in a suitable solvent or mixture of mutually miscible solvents. For reasons of their ingredients, method of preparation, or use, they do not fall into another group of products. [NIH] 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] Pharmacotherapy: A regimen of using appetite suppressant medications to manage obesity by decreasing appetite or increasing the feeling of satiety. These medications decrease appetite by increasing serotonin or catecholamine—two brain chemicals that affect mood and appetite. [NIH] Phenazopyridine: A local anesthetic that has been used in urinary tract disorders. Its use is limited by problems with toxicity (primarily blood disorders) and potential carcinogenicity. [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] Phospholipases: A class of enzymes that catalyze the hydrolysis of phosphoglycerides or glycerophosphatidates. EC 3.1.-. [NIH] Phospholipids: Lipids containing one or more phosphate groups, particularly those derived from either glycerol (phosphoglycerides; glycerophospholipids) or sphingosine (sphingolipids). They are polar lipids that are of great importance for the structure and function of cell membranes and are the most abundant of membrane lipids, although not stored in large amounts in the system. [NIH] Phosphorus: A non-metallic element that is found in the blood, muscles, nevers, bones, and teeth, and is a component of adenosine triphosphate (ATP; the primary energy source for the body's cells.) [NIH] Phosphorylated: Attached to a phosphate group. [NIH] Phosphorylation: The introduction of a phosphoryl group into a compound through the formation of an ester bond between the compound and a phosphorus moiety. [NIH] Photocoagulation: Using a special strong beam of light (laser) to seal off bleeding blood vessels such as in the eye. The laser can also burn away blood vessels that should not have grown in the eye. This is the main treatment for diabetic retinopathy. [NIH] Photoreceptor: Receptor capable of being activated by light stimuli, as a rod or cone cell of the eye. [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]
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Pigment: A substance that gives color to tissue. Pigments are responsible for the color of skin, eyes, and hair. [NIH] Pilocarpine: A slowly hydrolyzed muscarinic agonist with no nicotinic effects. Pilocarpine is used as a miotic and in the treatment of glaucoma. [NIH] Pilot study: The initial study examining a new method or treatment. [NIH] Pituitary Gland: A small, unpaired gland situated in the sella turcica tissue. It is connected to the hypothalamus by a short stalk. [NIH] Placenta: A highly vascular fetal organ through which the fetus absorbs oxygen and other nutrients and excretes carbon dioxide and other wastes. It begins to form about the eighth day of gestation when the blastocyst adheres to the decidua. [NIH] 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] Plasmids: Any extrachromosomal hereditary determinant. Plasmids are self-replicating circular molecules of DNA that are found in a variety of bacterial, archaeal, fungal, algal, and plant species. [NIH] Plasmin: A product of the lysis of plasminogen (profibrinolysin) by plasminogen activators. It is composed of two polypeptide chains, light (B) and heavy (A), with a molecular weight of 75,000. It is the major proteolytic enzyme involved in blood clot retraction or the lysis of fibrin and quickly inactivated by antiplasmins. EC 3.4.21.7. [NIH] Plasminogen: Precursor of fibrinolysin (plasmin). It is a single-chain beta-globulin of molecular weight 80-90,000 found mostly in association with fibrinogen in plasma; plasminogen activators change it to fibrinolysin. It is used in wound debriding and has been investigated as a thrombolytic agent. [NIH] Plasminogen Activators: A heterogeneous group of proteolytic enzymes that convert plasminogen to plasmin. They are concentrated in the lysosomes of most cells and in the vascular endothelium, particularly in the vessels of the microcirculation. EC 3.4.21.-. [NIH] Plasmodium: A genus of coccidian protozoa that comprise the malaria parasites of mammals. Four species infect humans (although occasional infections with primate malarias may occur). These are Plasmodium falciparum, Plasmodium malariae, P. ovale, and Plasmodium vivax. Species causing infection in vertebrates other than man include: Plasmodium berghei, Plasmodium chabaudi, P. vinckei, and Plasmodium yoelii in rodents; P. brasilianum, Plasmodium cynomolgi, and Plasmodium knowlesi in monkeys; and
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Plasmodium gallinaceum in chickens. [NIH] Plasmodium falciparum: A species of protozoa that is the causal agent of falciparum malaria. It is most prevalent in the tropics and subtropics. [NIH] Plasticity: In an individual or a population, the capacity for adaptation: a) through gene changes (genetic plasticity) or b) through internal physiological modifications in response to changes of environment (physiological plasticity). [NIH] 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] Platelet Factor 4: A high-molecular-weight proteoglycan-platelet factor complex which is released from blood platelets by thrombin. It acts as a mediator in the heparin-neutralizing capacity of the blood and plays a role in platelet aggregation. At high ionic strength (I=0.75), the complex dissociates into the active component (molecular weight 29,000) and the proteoglycan carrier (chondroitin 4-sulfate, molecular weight 350,000). The molecule exists in the form of a dimer consisting of 8 moles of platelet factor 4 and 2 moles of proteoglycan. [NIH]
Platelets: A type of blood cell that helps prevent bleeding by causing blood clots to form. Also called thrombocytes. [NIH] Platinum: Platinum. A heavy, soft, whitish metal, resembling tin, atomic number 78, atomic weight 195.09, symbol Pt. (From Dorland, 28th ed) It is used in manufacturing equipment for laboratory and industrial use. It occurs as a black powder (platinum black) and as a spongy substance (spongy platinum) and may have been known in Pliny's time as "alutiae". [NIH]
Pleura: The thin serous membrane enveloping the lungs and lining the thoracic cavity. [NIH] Pleural: A circumscribed area of hyaline whorled fibrous tissue which appears on the surface of the parietal pleura, on the fibrous part of the diaphragm or on the pleura in the interlobar fissures. [NIH] Pleural cavity: A space enclosed by the pleura (thin tissue covering the lungs and lining the interior wall of the chest cavity). It is bound by thin membranes. [NIH] Pleural Effusion: Presence of fluid in the pleural cavity resulting from excessive transudation or exudation from the pleural surfaces. It is a sign of disease and not a diagnosis in itself. [NIH] Pleurisy: Inflammation of the pleura, with exudation into its cavity and upon its surface. It may occur as either an acute or a chronic process. In acute pleurisy the pleura becomes reddened, then covered with an exudate of lymph, fibrin, and cellular elements (the dry stage); the disease may progress to the second stage, in which a copious exudation of serum occurs (stage of liquid effusion). The inflamed surfaces of the pleura tend to become united by adhesions, which are usually permanent. The symptoms are a stitch in the side, a chill, followed by fever and a dry cough. As effusion occurs there is an onset of dyspnea and a diminution of pain. The patient lies on the affected side. [EU] Poisoning: A condition or physical state produced by the ingestion, injection or inhalation
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of, or exposure to a deleterious agent. [NIH] Pollen: The male fertilizing element of flowering plants analogous to sperm in animals. It is released from the anthers as yellow dust, to be carried by insect or other vectors, including wind, to the ovary (stigma) of other flowers to produce the embryo enclosed by the seed. The pollens of many plants are allergenic. [NIH] Polycystic: An inherited disorder characterized by many grape-like clusters of fluid-filled cysts that make both kidneys larger over time. These cysts take over and destroy working kidney tissue. PKD may cause chronic renal failure and end-stage renal disease. [NIH] 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]
Polyhydroxyethyl Methacrylate: A biocompatible, hydrophilic, inert gel that is permeable to tissue fluids. It is used as an embedding medium for microscopy, as a coating for implants and prostheses, for contact lenses, as microspheres in adsorption research, etc. [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] Polypeptide: A peptide which on hydrolysis yields more than two amino acids; called tripeptides, tetrapeptides, etc. according to the number of amino acids contained. [EU] Polysaccharide: A type of carbohydrate. It contains sugar molecules that are linked together chemically. [NIH] Posterior: Situated in back of, or in the back part of, or affecting the back or dorsal surface of the body. In lower animals, it refers to the caudal end of the body. [EU] Postmenopausal: Refers to the time after menopause. Menopause is the time in a woman's life when menstrual periods stop permanently; also called "change of life." [NIH] Postnatal: Occurring after birth, with reference to the newborn. [EU] 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] Potentiates: A degree of synergism which causes the exposure of the organism to a harmful substance to worsen a disease already contracted. [NIH] Potentiating: A degree of synergism which causes the exposure of the organism to a harmful substance to worsen a disease already contracted. [NIH] Potentiation: An overall effect of two drugs taken together which is greater than the sum of the effects of each drug taken alone. [NIH] Practice Guidelines: Directions or principles presenting current or future rules of policy for the health care practitioner to assist him in patient care decisions regarding diagnosis, therapy, or related clinical circumstances. The guidelines may be developed by government
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agencies at any level, institutions, professional societies, governing boards, or by the convening of expert panels. The guidelines form a basis for the evaluation of all aspects of health care and delivery. [NIH] Precipitation: The act or process of precipitating. [EU] Precursor: Something that precedes. In biological processes, a substance from which another, usually more active or mature substance is formed. In clinical medicine, a sign or symptom that heralds another. [EU] Prenatal: Existing or occurring before birth, with reference to the fetus. [EU] Presumptive: A treatment based on an assumed diagnosis, prior to receiving confirmatory laboratory test results. [NIH] Prevalence: The total number of cases of a given disease in a specified population at a designated time. It is differentiated from incidence, which refers to the number of new cases in the population at a given time. [NIH] Prickle: Several layers of the epidermis where the individual cells are connected by cell bridges. [NIH] Prion: Small proteinaceous infectious particles that resist inactivation by procedures modifying nucleic acids and contain an abnormal isoform of a cellular protein which is a major and necessary component. [NIH] Probe: An instrument used in exploring cavities, or in the detection and dilatation of strictures, or in demonstrating the potency of channels; an elongated instrument for exploring or sounding body cavities. [NIH] Procaine: A local anesthetic of the ester type that has a slow onset and a short duration of action. It is mainly used for infiltration anesthesia, peripheral nerve block, and spinal block. (From Martindale, The Extra Pharmacopoeia, 30th ed, p1016). [NIH] Procollagen: A biosynthetic precursor of collagen containing additional amino acid sequences at the amino-terminal ends of the three polypeptide chains. Protocollagen, a precursor of procollagen consists of procollagen peptide chains in which proline and lysine have not yet been hydroxylated. [NIH] 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] 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] Pronase: A proteolytic enzyme obtained from Streptomyces griseus. [NIH] Prone: Having the front portion of the body downwards. [NIH]
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Pro-Opiomelanocortin: A precursor protein, MW 30,000, synthesized mainly in the anterior pituitary gland but also found in the hypothalamus, brain, and several peripheral tissues. It incorporates the amino acid sequences of ACTH and beta-lipotropin. These two hormones, in turn, contain the biologically active peptides MSH, corticotropin-like intermediate lobe peptide, alpha-lipotropin, endorphins, and methionine enkephalin. [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] Prosencephalon: The part of the brain developed from the most rostral of the three primary vesicles of the embryonic neural tube and consisting of the diencephalon and telencephalon. [NIH]
Prostaglandin: Any of a group of components derived from unsaturated 20-carbon fatty acids, primarily arachidonic acid, via the cyclooxygenase pathway that are extremely potent mediators of a diverse group of physiologic processes. The abbreviation for prostaglandin is PG; specific compounds are designated by adding one of the letters A through I to indicate the type of substituents found on the hydrocarbon skeleton and a subscript (1, 2 or 3) to indicate the number of double bonds in the hydrocarbon skeleton e.g., PGE2. The predominant naturally occurring prostaglandins all have two double bonds and are synthesized from arachidonic acid (5,8,11,14-eicosatetraenoic acid) by the pathway shown in the illustration. The 1 series and 3 series are produced by the same pathway with fatty acids having one fewer double bond (8,11,14-eicosatrienoic acid or one more double bond (5,8,11,14,17-eicosapentaenoic acid) than arachidonic acid. The subscript a or ß indicates the configuration at C-9 (a denotes a substituent below the plane of the ring, ß, above the plane). The naturally occurring PGF's have the a configuration, e.g., PGF2a. All of the prostaglandins act by binding to specific cell-surface receptors causing an increase in the level of the intracellular second messenger cyclic AMP (and in some cases cyclic GMP also). The effect produced by the cyclic AMP increase depends on the specific cell type. In some cases there is also a positive feedback effect. Increased cyclic AMP increases prostaglandin synthesis leading to further increases in cyclic AMP. [EU] Prostaglandins A: (13E,15S)-15-Hydroxy-9-oxoprosta-10,13-dien-1-oic acid (PGA(1)); (5Z,13E,15S)-15-hydroxy-9-oxoprosta-5,10,13-trien-1-oic acid (PGA(2)); (5Z,13E,15S,17Z)-15hydroxy-9-oxoprosta-5,10,13,17-tetraen-1-oic acid (PGA(3)). A group of naturally occurring secondary prostaglandins derived from PGE. PGA(1) and PGA(2) as well as their 19hydroxy derivatives are found in many organs and tissues. [NIH] Prostaglandins D: Physiologically active prostaglandins found in many tissues and organs. They show pressor activity, are mediators of inflammation, and have potential antithrombotic effects. [NIH] 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] Prostatectomy: Complete or partial surgical removal of the prostate. Three primary approaches are commonly employed: suprapubic - removal through an incision above the pubis and through the urinary bladder; retropubic - as for suprapubic but without entering the urinary bladder; and transurethral (transurethral resection of prostate). [NIH] Prosthesis: An artificial replacement of a part of the body. [NIH] Protease: Proteinase (= any enzyme that catalyses the splitting of interior peptide bonds in a protein). [EU] Protease Inhibitors: Compounds which inhibit or antagonize biosynthesis or actions of
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proteases (endopeptidases). [NIH] Protective Agents: Synthetic or natural substances which are given to prevent a disease or disorder or are used in the process of treating a disease or injury due to a poisonous agent. [NIH]
Protein Binding: The process in which substances, either endogenous or exogenous, bind to proteins, peptides, enzymes, protein precursors, or allied compounds. Specific proteinbinding measures are often used as assays in diagnostic assessments. [NIH] Protein C: A vitamin-K dependent zymogen present in the blood, which, upon activation by thrombin and thrombomodulin exerts anticoagulant properties by inactivating factors Va and VIIIa at the rate-limiting steps of thrombin formation. [NIH] Protein Conformation: The characteristic 3-dimensional shape of a protein, including the secondary, supersecondary (motifs), tertiary (domains) and quaternary structure of the peptide chain. Quaternary protein structure describes the conformation assumed by multimeric proteins (aggregates of more than one polypeptide chain). [NIH] Protein Folding: A rapid biochemical reaction involved in the formation of proteins. It begins even before a protein has been completely synthesized and proceeds through discrete intermediates (primary, secondary, and tertiary structures) before the final structure (quaternary structure) is developed. [NIH] Protein Kinases: A family of enzymes that catalyze the conversion of ATP and a protein to ADP and a phosphoprotein. EC 2.7.1.37. [NIH] Protein S: The vitamin K-dependent cofactor of activated protein C. Together with protein C, it inhibits the action of factors VIIIa and Va. A deficiency in protein S can lead to recurrent venous and arterial thrombosis. [NIH] Proteins: Polymers of amino acids linked by peptide bonds. The specific sequence of amino acids determines the shape and function of the protein. [NIH] Proteoglycan: A molecule that contains both protein and glycosaminoglycans, which are a type of polysaccharide. Proteoglycans are found in cartilage and other connective tissues. [NIH]
Proteolytic: 1. Pertaining to, characterized by, or promoting proteolysis. 2. An enzyme that promotes proteolysis (= the splitting of proteins by hydrolysis of the peptide bonds with formation of smaller polypeptides). [EU] Prothrombin: A plasma protein that is the inactive precursor of thrombin. It is converted to thrombin by a prothrombin activator complex consisting of factor Xa, factor V, phospholipid, and calcium ions. Deficiency of prothrombin leads to hypoprothrombinemia. [NIH]
Protocol: The detailed plan for a clinical trial that states the trial's rationale, purpose, drug or vaccine dosages, length of study, routes of administration, who may participate, and other aspects of trial design. [NIH] Protons: Stable elementary particles having the smallest known positive charge, found in the nuclei of all elements. The proton mass is less than that of a neutron. A proton is the nucleus of the light hydrogen atom, i.e., the hydrogen ion. [NIH] 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] Proximal: Nearest; closer to any point of reference; opposed to distal. [EU] Pruritic: Pertaining to or characterized by pruritus. [EU]
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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] Psychology: The science dealing with the study of mental processes and behavior in man and animals. [NIH] Psychomotor: Pertaining to motor effects of cerebral or psychic activity. [EU] Public Health: Branch of medicine concerned with the prevention and control of disease and disability, and the promotion of physical and mental health of the population on the international, national, state, or municipal level. [NIH] Public Policy: A course or method of action selected, usually by a government, from among alternatives to guide and determine present and future decisions. [NIH] Publishing: "The business or profession of the commercial production and issuance of literature" (Webster's 3d). It includes the publisher, publication processes, editing and editors. Production may be by conventional printing methods or by electronic publishing. [NIH]
Pulmonary: Relating to the lungs. [NIH] Pulmonary Fibrosis: Chronic inflammation and progressive fibrosis of the pulmonary alveolar walls, with steadily progressive dyspnea, resulting finally in death from oxygen lack or right heart failure. [NIH] Pulmonary hypertension: Abnormally high blood pressure in the arteries of the lungs. [NIH] Pulse: The rhythmical expansion and contraction of an artery produced by waves of pressure caused by the ejection of blood from the left ventricle of the heart as it contracts. [NIH]
Pupil: The aperture in the iris through which light passes. [NIH] 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] Pyridoxal: 3-Hydroxy-5-(hydroxymethyl)-2-methyl-4- pyridinecarboxaldehyde. [NIH] Quality of Life: A generic concept reflecting concern with the modification and enhancement of life attributes, e.g., physical, political, moral and social environment. [NIH] Quaternary: 1. Fourth in order. 2. Containing four elements or groups. [EU] 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] 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
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sufficiently so as to achieve the status of a taxon. [NIH] Radiation: Emission or propagation of electromagnetic energy (waves/rays), or the waves/rays themselves; a stream of electromagnetic particles (electrons, neutrons, protons, alpha particles) or a mixture of these. The most common source is the sun. [NIH] Radiation therapy: The use of high-energy radiation from x-rays, gamma rays, neutrons, and other sources to kill cancer cells and shrink tumors. Radiation may come from a machine outside the body (external-beam radiation therapy), or it may come from radioactive material placed in the body in the area near cancer cells (internal radiation therapy, implant radiation, or brachytherapy). Systemic radiation therapy uses a radioactive substance, such as a radiolabeled monoclonal antibody, that circulates throughout the body. Also called radiotherapy. [NIH] Radical prostatectomy: Surgery to remove the entire prostate. The two types of radical prostatectomy are retropubic prostatectomy and perineal prostatectomy. [NIH] Radioactive: Giving off radiation. [NIH] Radiochemical: The proportion of the total activity of the radionuclide in the sample considered, which is due to the nuclide in the stated chemical form. [NIH] Radioimmunotherapy: Radiotherapy where cytotoxic radionuclides are linked to antibodies in order to deliver toxins directly to tumor targets. Therapy with targeted radiation rather than antibody-targeted toxins (immunotoxins) has the advantage that adjacent tumor cells, which lack the appropriate antigenic determinants, can be destroyed by radiation cross-fire. Radioimmunotherapy is sometimes called targeted radiotherapy, but this latter term can also refer to radionuclides linked to non-immune molecules (radiotherapy). [NIH] Radioisotope: An unstable element that releases radiation as it breaks down. Radioisotopes can be used in imaging tests or as a treatment for cancer. [NIH] Radiolabeled: Any compound that has been joined with a radioactive substance. [NIH] Radiological: Pertaining to radiodiagnostic and radiotherapeutic procedures, and interventional radiology or other planning and guiding medical radiology. [NIH] 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] Raloxifene: A second generation selective estrogen receptor modulator (SERM) used to prevent osteoporosis in postmenopausal women. It has estrogen agonist effects on bone and cholesterol metabolism but behaves as a complete estrogen antagonist on mammary gland and uterine tissue. [NIH] Randomized: Describes an experiment or clinical trial in which animal or human subjects are assigned by chance to separate groups that compare different treatments. [NIH] Randomized clinical trial: A study in which the participants are assigned by chance to separate groups that compare different treatments; neither the researchers nor the participants can choose which group. Using chance to assign people to groups means that the groups will be similar and that the treatments they receive can be compared objectively. At the time of the trial, it is not known which treatment is best. It is the patient's choice to be in a randomized trial. [NIH] RANTES: A chemokine that is a chemoattractant for eosinophils, monocytes, and
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lymphocytes. It is a potent and selective eosinophil chemotaxin that is stored in and released from platelets and activated T-cells. [NIH] Reactive Oxygen Species: Reactive intermediate oxygen species including both radicals and non-radicals. These substances are constantly formed in the human body and have been shown to kill bacteria and inactivate proteins, and have been implicated in a number of diseases. Scientific data exist that link the reactive oxygen species produced by inflammatory phagocytes to cancer development. [NIH] Reagent: A substance employed to produce a chemical reaction so as to detect, measure, produce, etc., other substances. [EU] Receptor: A molecule inside or on the surface of a cell that binds to a specific substance and causes a specific physiologic effect in the cell. [NIH] Receptors, Serotonin: Cell-surface proteins that bind serotonin and trigger intracellular changes which influence the behavior of cells. Several types of serotonin receptors have been recognized which differ in their pharmacology, molecular biology, and mode of action. [NIH] Recombinant: A cell or an individual with a new combination of genes not found together in either parent; usually applied to linked genes. [EU] Recombination: The formation of new combinations of genes as a result of segregation in crosses between genetically different parents; also the rearrangement of linked genes due to crossing-over. [NIH] Reconstitution: 1. A type of regeneration in which a new organ forms by the rearrangement of tissues rather than from new formation at an injured surface. 2. The restoration to original form of a substance previously altered for preservation and storage, as the restoration to a liquid state of blood serum or plasma that has been dried and stored. [EU] Recovery of Function: A partial or complete return to the normal or proper physiologic activity of an organ or part following disease or trauma. [NIH] Rectum: The last 8 to 10 inches of the large intestine. [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] 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] Refractive Errors: Deviations from the average or standard indices of refraction of the eye through its dioptric or refractive apparatus. [NIH] Regeneration: The natural renewal of a structure, as of a lost tissue or part. [EU] Regimen: A treatment plan that specifies the dosage, the schedule, and the duration of treatment. [NIH] Regurgitation: A backward flowing, as the casting up of undigested food, or the backward flowing of blood into the heart, or between the chambers of the heart when a valve is incompetent. [EU] Relaxant: 1. Lessening or reducing tension. 2. An agent that lessens tension. [EU] 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
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angiotensin I. EC 3.4.23.15. (Formerly EC 3.4.99.19). [NIH] Renin-Angiotensin System: A system consisting of renin, angiotensin-converting enzyme, and angiotensin II. Renin, an enzyme produced in the kidney, acts on angiotensinogen, an alpha-2 globulin produced by the liver, forming angiotensin I. The converting enzyme contained in the lung acts on angiotensin I in the plasma converting it to angiotensin II, the most powerful directly pressor substance known. It causes contraction of the arteriolar smooth muscle and has other indirect actions mediated through the adrenal cortex. [NIH] Repopulation: The replacement of functional cells, usually by proliferation, following or during irradiation. [NIH] Research Support: Financial support of research activities. [NIH] Resorption: The loss of substance through physiologic or pathologic means, such as loss of dentin and cementum of a tooth, or of the alveolar process of the mandible or maxilla. [EU] Respiration: The act of breathing with the lungs, consisting of inspiration, or the taking into the lungs of the ambient air, and of expiration, or the expelling of the modified air which contains more carbon dioxide than the air taken in (Blakiston's Gould Medical Dictionary, 4th ed.). This does not include tissue respiration (= oxygen consumption) or cell respiration (= cell respiration). [NIH] Response rate: The percentage of patients whose cancer shrinks or disappears after treatment. [NIH] Restoration: Broad term applied to any inlay, crown, bridge or complete denture which restores or replaces loss of teeth or oral tissues. [NIH] Reticular: Coarse-fibered, netlike dermis layer. [NIH] Retina: The ten-layered nervous tissue membrane of the eye. It is continuous with the optic nerve and receives images of external objects and transmits visual impulses to the brain. Its outer surface is in contact with the choroid and the inner surface with the vitreous body. The outer-most layer is pigmented, whereas the inner nine layers are transparent. [NIH] Retinal: 1. Pertaining to the retina. 2. The aldehyde of retinol, derived by the oxidative enzymatic splitting of absorbed dietary carotene, and having vitamin A activity. In the retina, retinal combines with opsins to form visual pigments. One isomer, 11-cis retinal combines with opsin in the rods (scotopsin) to form rhodopsin, or visual purple. Another, all-trans retinal (trans-r.); visual yellow; xanthopsin) results from the bleaching of rhodopsin by light, in which the 11-cis form is converted to the all-trans form. Retinal also combines with opsins in the cones (photopsins) to form the three pigments responsible for colour vision. Called also retinal, and retinene1. [EU] Retinoblastoma: An eye cancer that most often occurs in children younger than 5 years. It occurs in hereditary and nonhereditary (sporadic) forms. [NIH] Retinoids: Derivatives of vitamin A. Used clinically in the treatment of severe cystic acne, psoriasis, and other disorders of keratinization. Their possible use in the prophylaxis and treatment of cancer is being actively explored. [NIH] Retinol: Vitamin A. It is essential for proper vision and healthy skin and mucous membranes. Retinol is being studied for cancer prevention; it belongs to the family of drugs called retinoids. [NIH] Retropubic: A potential space between the urinary bladder and the symphisis and body of the pubis. [NIH] Retropubic prostatectomy: Surgery to remove the prostate through an incision made in the abdominal wall. [NIH]
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Reverberant: The sound field prevailing in a large enclosure with moderately reflecting surfaces. [NIH] Rheumatic Diseases: Disorders of connective tissue, especially the joints and related structures, characterized by inflammation, degeneration, or metabolic derangement. [NIH] Rheumatism: A group of disorders marked by inflammation or pain in the connective tissue structures of the body. These structures include bone, cartilage, and fat. [NIH] Rheumatoid: Resembling rheumatism. [EU] Rheumatoid arthritis: A form of arthritis, the cause of which is unknown, although infection, hypersensitivity, hormone imbalance and psychologic stress have been suggested as possible causes. [NIH] Rheumatology: A subspecialty of internal medicine concerned with the study of inflammatory or degenerative processes and metabolic derangement of connective tissue structures which pertain to a variety of musculoskeletal disorders, such as arthritis. [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] Rod: A reception for vision, located in the retina. [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] 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] 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] Sarcolemma: The plasma membrane of a smooth, striated, or cardiac muscle fiber. [NIH] Scatter: The extent to which relative success and failure are divergently manifested in qualitatively different tests. [NIH] Schwannoma: A tumor of the peripheral nervous system that begins in the nerve sheath (protective covering). It is almost always benign, but rare malignant schwannomas have been reported. [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] Scleritis: Refers to any inflammation of the sclera including episcleritis, a benign condition affecting only the episclera, which is generally short-lived and easily treated. Classic
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scleritis, on the other hand, affects deeper tissue and is characterized by higher rates of visual acuity loss and even mortality, particularly in necrotizing form. Its characteristic symptom is severe and general head pain. Scleritis has also been associated with systemic collagen disease. Etiology is unknown but is thought to involve a local immune response. Treatment is difficult and includes administration of anti-inflammatory and immunosuppressive agents such as corticosteroids. Inflammation of the sclera may also be secondary to inflammation of adjacent tissues, such as the conjunctiva. [NIH] Scleroderma: A chronic disorder marked by hardening and thickening of the skin. Scleroderma can be localized or it can affect the entire body (systemic). [NIH] Sclerosis: A pathological process consisting of hardening or fibrosis of an anatomical structure, often a vessel or a nerve. [NIH] Screening: Checking for disease when there are no symptoms. [NIH] Scrotum: In males, the external sac that contains the testicles. [NIH] Sea Urchins: Somewhat flattened, globular echinoderms of the class Echinoidea, having thin, brittle shells of calcareous plates. [NIH] Sebaceous: Gland that secretes sebum. [NIH] Sebaceous gland: Gland that secretes sebum. [NIH] Secondary tumor: Cancer that has spread from the organ in which it first appeared to another organ. For example, breast cancer cells may spread (metastasize) to the lungs and cause the growth of a new tumor. When this happens, the disease is called metastatic breast cancer, and the tumor in the lungs is called a secondary tumor. Also called secondary cancer. [NIH] Secretion: 1. The process of elaborating a specific product as a result of the activity of a gland; this activity may range from separating a specific substance of the blood to the elaboration of a new chemical substance. 2. Any substance produced by secretion. [EU] 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] Selective estrogen receptor modulator: SERM. A drug that acts like estrogen on some tissues, but blocks the effect of estrogen on other tissues. Tamoxifen and raloxifene are SERMs. [NIH] Selenium: An element with the atomic symbol Se, atomic number 34, and atomic weight 78.96. It is an essential micronutrient for mammals and other animals but is toxic in large amounts. Selenium protects intracellular structures against oxidative damage. It is an essential component of glutathione peroxidase. [NIH] Self Care: Performance of activities or tasks traditionally performed by professional health care providers. The concept includes care of oneself or one's family and friends. [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] Senile: Relating or belonging to old age; characteristic of old age; resulting from infirmity of
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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] Sequester: A portion of dead bone which has become detached from the healthy bone tissue, as occurs in necrosis. [NIH] Serine: A non-essential amino acid occurring in natural form as the L-isomer. It is synthesized from glycine or threonine. It is involved in the biosynthesis of purines, pyrimidines, and other amino acids. [NIH] Serotonin: A biochemical messenger and regulator, synthesized from the essential amino acid L-tryptophan. In humans it is found primarily in the central nervous system, gastrointestinal tract, and blood platelets. Serotonin mediates several important physiological functions including neurotransmission, gastrointestinal motility, hemostasis, and cardiovascular integrity. Multiple receptor families (receptors, serotonin) explain the broad physiological actions and distribution of this biochemical mediator. [NIH] Serrata: The serrated anterior border of the retina located approximately 8.5 mm from the limbus and adjacent to the pars plana of the ciliary body. [NIH] 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] 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] Sharks: A group of elongate elasmobranchs. Sharks are mostly marine fish, with certain species large and voracious. [NIH] Shedding: Release of infectious particles (e. g., bacteria, viruses) into the environment, for example by sneezing, by fecal excretion, or from an open lesion. [NIH] 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
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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] 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] 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] Skin Care: Maintenance of the hygienic state of the skin under optimal conditions of cleanliness and comfort. Effective in skin care are proper washing, bathing, cleansing, and the use of soaps, detergents, oils, etc. In various disease states, therapeutic and protective solutions and ointments are useful. The care of the skin is particularly important in various occupations, in exposure to sunlight, in neonates, and in decubitus ulcer. [NIH] Skin graft: Skin that is moved from one part of the body to another. [NIH] Skull: The skeleton of the head including the bones of the face and the bones enclosing the brain. [NIH] Sludge: A clump of agglutinated red blood cells. [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] Social Environment: The aggregate of social and cultural institutions, forms, patterns, and processes that influence the life of an individual or community. [NIH] Sodium: An element that is a member of the alkali group of metals. It has the atomic symbol Na, atomic number 11, and atomic weight 23. With a valence of 1, it has a strong affinity for oxygen and other nonmetallic elements. Sodium provides the chief cation of the extracellular body fluids. Its salts are the most widely used in medicine. (From Dorland, 27th ed) Physiologically the sodium ion plays a major role in blood pressure regulation, maintenance of fluid volume, and electrolyte balance. [NIH]
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Sodium Bicarbonate: A white, crystalline powder that is commonly used as a pH buffering agent, an electrolyte replenisher, systemic alkalizer and in topical cleansing solutions. [NIH] Soft tissue: Refers to muscle, fat, fibrous tissue, blood vessels, or other supporting tissue of the body. [NIH] Solid tumor: Cancer of body tissues other than blood, bone marrow, or the lymphatic system. [NIH] Solvent: 1. Dissolving; effecting a solution. 2. A liquid that dissolves or that is capable of dissolving; the component of a solution that is present in greater amount. [EU] Soma: The body as distinct from the mind; all the body tissue except the germ cells; all the axial body. [NIH] Somatic: 1. Pertaining to or characteristic of the soma or body. 2. Pertaining to the body wall in contrast to the viscera. [EU] 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] Soybean Oil: Oil from soybean or soybean plant. [NIH] Specialist: In medicine, one who concentrates on 1 special branch of medical science. [NIH] Species: A taxonomic category subordinate to a genus (or subgenus) and superior to a subspecies or variety, composed of individuals possessing common characters distinguishing them from other categories of individuals of the same taxonomic level. In taxonomic nomenclature, species are designated by the genus name followed by a Latin or Latinized adjective or noun. [EU] Specificity: Degree of selectivity shown by an antibody with respect to the number and types of antigens with which the antibody combines, as well as with respect to the rates and the extents of these reactions. [NIH] Sperm: The fecundating fluid of the male. [NIH] Sphincter: A ringlike band of muscle fibres that constricts a passage or closes a natural orifice; called also musculus sphincter. [EU] Spinal cord: The main trunk or bundle of nerves running down the spine through holes in the spinal bone (the vertebrae) from the brain to the level of the lower back. [NIH] Spinal Cord Injuries: Penetrating and non-penetrating injuries to the spinal cord resulting from traumatic external forces (e.g., wounds, gunshot; whiplash injuries; etc.). [NIH] Spinal Nerves: The 31 paired peripheral nerves formed by the union of the dorsal and ventral spinal roots from each spinal cord segment. The spinal nerve plexuses and the spinal roots are also included. [NIH] Spinous: Like a spine or thorn in shape; having spines. [NIH] Spleen: An organ that is part of the lymphatic system. The spleen produces lymphocytes, filters the blood, stores blood cells, and destroys old blood cells. It is located on the left side of the abdomen near the stomach. [NIH] Splenomegaly: Enlargement of the spleen. [NIH] Sporadic: Neither endemic nor epidemic; occurring occasionally in a random or isolated manner. [EU] Sputum: The material expelled from the respiratory passages by coughing or clearing the
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throat. [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] Stabilization: The creation of a stable state. [EU] Stasis: A word termination indicating the maintenance of (or maintaining) a constant level; preventing increase or multiplication. [EU] 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] 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] Stents: Devices that provide support for tubular structures that are being anastomosed or for body cavities during skin grafting. [NIH] Sterile: Unable to produce children. [NIH] 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] 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] Stroke: Sudden loss of function of part of the brain because of loss of blood flow. Stroke may be caused by a clot (thrombosis) or rupture (hemorrhage) of a blood vessel to the brain. [NIH] Stroma: The middle, thickest layer of tissue in the cornea. [NIH] Stromal: Large, veil-like cell in the bone marrow. [NIH] Stupor: Partial or nearly complete unconsciousness, manifested by the subject's responding
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only to vigorous stimulation. Also, in psychiatry, a disorder marked by reduced responsiveness. [EU] Subacute: Somewhat acute; between acute and chronic. [EU] Subclinical: Without clinical manifestations; said of the early stage(s) of an infection or other disease or abnormality before symptoms and signs become apparent or detectable by clinical examination or laboratory tests, or of a very mild form of an infection or other disease or abnormality. [EU] Subcutaneous: Beneath the skin. [NIH] Subiculum: A region of the hippocampus that projects to other areas of the brain. [NIH] 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] Subtilisin: A serine endopeptidase isolated from Bacillus subtilis. It hydrolyzes proteins with broad specificity for peptide bonds, and a preference for a large uncharged residue in P1. It also hydrolyzes peptide amides. (From Enzyme Nomenclature, 1992) EC 3.4.21.62. [NIH]
Sulfates: Inorganic salts of sulfuric acid. [NIH] Sulfotransferases: Enzymes which transfer sulfate groups to various acceptor molecules. They are involved in posttranslational sulfation of proteins and sulfate conjugation of exogenous chemicals and bile acids. EC 2.8.2. [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] Sulfuric acid: A strong acid that, when concentrated is extemely corrosive to the skin and mucous membranes. It is used in making fertilizers, dyes, electroplating, and industrial explosives. [NIH] Supplementation: Adding nutrients to the diet. [NIH] Suppositories: A small cone-shaped medicament having cocoa butter or gelatin at its basis and usually intended for the treatment of local conditions in the rectum. [NIH] Suppression: A conscious exclusion of disapproved desire contrary with repression, in which the process of exclusion is not conscious. [NIH] Suppressive: Tending to suppress : effecting suppression; specifically : serving to suppress activity, function, symptoms. [EU] Surfactant: A fat-containing protein in the respiratory passages which reduces the surface tension of pulmonary fluids and contributes to the elastic properties of pulmonary tissue. [NIH]
Sympathomimetic: 1. Mimicking the effects of impulses conveyed by adrenergic
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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] 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] Synovitis: Inflammation of a synovial membrane. It is usually painful, particularly on motion, and is characterized by a fluctuating swelling due to effusion within a synovial sac. Synovitis is qualified as fibrinous, gonorrhoeal, hyperplastic, lipomatous, metritic, puerperal, rheumatic, scarlatinal, syphilitic, tuberculous, urethral, etc. [EU] Systemic: Affecting the entire body. [NIH] Systemic disease: Disease that affects the whole body. [NIH] Systolic: Indicating the maximum arterial pressure during contraction of the left ventricle of the heart. [EU] Talus: The second largest of the tarsal bones and occupies the middle and upper part of the tarsus. [NIH] Tarsal Bones: The seven bones which form the tarsus - namely, calcaneus, talus, cuboid, navicular, and first, second and third cuneiforms. The tarsus is a skeletal part of the foot. [NIH]
Tarsus: The region of the articulation between the foot and the leg. [NIH] Tear Gases: Gases that irritate the eyes, throat, or skin. Severe lacrimation develops upon irritation of the eyes. [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
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cerebrum (Anthoney, 1994). [NIH] Telomerase: Essential ribonucleoprotein reverse transcriptase that adds telomeric DNA to the ends of eukaryotic chromosomes. Telomerase appears to be repressed in normal human somatic tissues but reactivated in cancer, and thus may be necessary for malignant transformation. EC 2.7.7.-. [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] Tendonitis: Inflammation of tendons attached to the biceps muscle, i. e. the main flexor muscle of the upper arm. [NIH] Terminalis: A groove on the lateral surface of the right atrium. [NIH] Testicles: The two egg-shaped glands found inside the scrotum. They produce sperm and male hormones. Also called testes. [NIH] Testicular: Pertaining to a testis. [EU] Testis: Either of the paired male reproductive glands that produce the male germ cells and the male hormones. [NIH] 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] Thermoregulation: Heat regulation. [EU] Thigh: A leg; in anatomy, any elongated process or part of a structure more or less comparable to a leg. [NIH] Thimerosal: A topical antiseptic used on skin and mucous membranes. It is also used as a preservative in pharmaceuticals. [NIH] Thoracic: Having to do with the chest. [NIH] Thorax: A part of the trunk between the neck and the abdomen; the chest. [NIH] Threonine: An essential amino acid occurring naturally in the L-form, which is the active form. It is found in eggs, milk, gelatin, and other proteins. [NIH] Threshold: For a specified sensory modality (e. g. light, sound, vibration), the lowest level (absolute threshold) or smallest difference (difference threshold, difference limen) or intensity of the stimulus discernible in prescribed conditions of stimulation. [NIH] Thrombin: An enzyme formed from prothrombin that converts fibrinogen to fibrin. (Dorland, 27th ed) EC 3.4.21.5. [NIH] 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] Thrombolytic: 1. Dissolving or splitting up a thrombus. 2. A thrombolytic agent. [EU] Thrombomodulin: A cell surface glycoprotein of endothelial cells that binds thrombin and
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serves as a cofactor in the activation of protein C and its regulation of blood coagulation. [NIH]
Thrombosis: The formation or presence of a blood clot inside a blood vessel. [NIH] Thromboxanes: Physiologically active compounds found in many organs of the body. They are formed in vivo from the prostaglandin endoperoxides and cause platelet aggregation, contraction of arteries, and other biological effects. Thromboxanes are important mediators of the actions of polyunsaturated fatty acids transformed by cyclooxygenase. [NIH] Thrombus: An aggregation of blood factors, primarily platelets and fibrin with entrapment of cellular elements, frequently causing vascular obstruction at the point of its formation. Some authorities thus differentiate thrombus formation from simple coagulation or clot formation. [EU] Thymidine: A chemical compound found in DNA. Also used as treatment for mucositis. [NIH]
Thymus: An organ that is part of the lymphatic system, in which T lymphocytes grow and multiply. The thymus is in the chest behind the breastbone. [NIH] Thyroid: A gland located near the windpipe (trachea) that produces thyroid hormone, which helps regulate growth and metabolism. [NIH] 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] Tinnitus: Sounds that are perceived in the absence of any external noise source which may take the form of buzzing, ringing, clicking, pulsations, and other noises. Objective tinnitus refers to noises generated from within the ear or adjacent structures that can be heard by other individuals. The term subjective tinnitus is used when the sound is audible only to the affected individual. Tinnitus may occur as a manifestation of cochlear diseases; vestibulocochlear nerve diseases; intracranial hypertension; craniocerebral trauma; and other conditions. [NIH] Tissue: A group or layer of cells that are alike in type and work together to perform a specific function. [NIH] Tissue Culture: Maintaining or growing of tissue, organ primordia, or the whole or part of an organ in vitro so as to preserve its architecture and/or function (Dorland, 28th ed). Tissue culture includes both organ culture and cell culture. [NIH] Tissue Distribution: Accumulation of a drug or chemical substance in various organs (including those not relevant to its pharmacologic or therapeutic action). This distribution depends on the blood flow or perfusion rate of the organ, the ability of the drug to penetrate organ membranes, tissue specificity, protein binding. The distribution is usually expressed as tissue to plasma ratios. [NIH] Tissue Plasminogen Activator: A proteolytic enzyme in the serine protease family found in many tissues which converts plasminogen to plasmin. It has fibrin-binding activity and is immunologically different from urinary plasminogen activator. The primary sequence, composed of 527 amino acids, is identical in both the naturally occurring and synthetic proteases. EC 3.4.21.68. [NIH] Tonsils: Small masses of lymphoid tissue on either side of the throat. [NIH] 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
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usually cause unwanted side effects. [NIH] Toxicity: The quality of being poisonous, especially the degree of virulence of a toxic microbe or of a poison. [EU] Toxicokinetics: Study of the absorption, distribution, metabolism, and excretion of test substances. [NIH] Toxicology: The science concerned with the detection, chemical composition, and pharmacologic action of toxic substances or poisons and the treatment and prevention of toxic manifestations. [NIH] Toxins: Specific, characterizable, poisonous chemicals, often proteins, with specific biological properties, including immunogenicity, produced by microbes, higher plants, or animals. [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] Tragacanth: Powdered exudate from Astragalus gummifer and related plants. It forms gelatinous mass in water. Tragacanth is used as suspending agent, excipient or emulsifier in foods, cosmetics and pharmaceuticals. It has also been used as a bulk-forming laxative. [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] Transforming Growth Factor beta: A factor synthesized in a wide variety of tissues. It acts synergistically with TGF-alpha in inducing phenotypic transformation and can also act as a negative autocrine growth factor. TGF-beta has a potential role in embryonal development, cellular differentiation, hormone secretion, and immune function. TGF-beta is found mostly as homodimer forms of separate gene products TGF-beta1, TGF-beta2 or TGF-beta3. Heterodimers composed of TGF-beta1 and 2 (TGF-beta1.2) or of TGF-beta2 and 3 (TGFbeta2.3) have been isolated. The TGF-beta proteins are synthesized as precursor proteins. [NIH]
Transgenes: Genes that are introduced into an organism using gene transfer techniques. [NIH]
Translation: The process whereby the genetic information present in the linear sequence of ribonucleotides in mRNA is converted into a corresponding sequence of amino acids in a protein. It occurs on the ribosome and is unidirectional. [NIH] Translational: The cleavage of signal sequence that directs the passage of the protein
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through a cell or organelle membrane. [NIH] Translocation: The movement of material in solution inside the body of the plant. [NIH] Transmitter: A chemical substance which effects the passage of nerve impulses from one cell to the other at the synapse. [NIH] Transplantation: Transference of a tissue or organ, alive or dead, within an individual, between individuals of the same species, or between individuals of different species. [NIH] Trauma: Any injury, wound, or shock, must frequently physical or structural shock, producing a disturbance. [NIH] Tricuspid Atresia: Absence of the orifice between the right atrium and ventricle, with the presence of an atrial defect through which all the systemic venous return reaches the left heart. As a result, there is left ventricular hypertrophy because the right ventricle is absent or not functional. [NIH] Trisomy: The possession of a third chromosome of any one type in an otherwise diploid cell. [NIH]
Trophic: Of or pertaining to nutrition. [EU] Trypsin: A serine endopeptidase that is formed from trypsinogen in the pancreas. It is converted into its active form by enteropeptidase in the small intestine. It catalyzes hydrolysis of the carboxyl group of either arginine or lysine. EC 3.4.21.4. [NIH] Tryptophan: An essential amino acid that is necessary for normal growth in infants and for nitrogen balance in adults. It is a precursor serotonin and niacin. [NIH] 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] Tubulin: A microtubule subunit protein found in large quantities in mammalian brain. It has also been isolated from sperm flagella, cilia, and other sources. Structurally, the protein is a dimer with a molecular weight of approximately 120,000 and a sedimentation coefficient of 5.8S. It binds to colchicine, vincristine, and vinblastine. [NIH] Tumor marker: A substance sometimes found in an increased amount in the blood, other body fluids, or tissues and which may mean that a certain type of cancer is in the body. Examples of tumor markers include CA 125 (ovarian cancer), CA 15-3 (breast cancer), CEA (ovarian, lung, breast, pancreas, and gastrointestinal tract cancers), and PSA (prostate cancer). Also called biomarker. [NIH] 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] Tympanic membrane: A thin, tense membrane forming the greater part of the outer wall of the tympanic cavity and separating it from the external auditory meatus; it constitutes the boundary between the external and middle ear. [NIH] 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] Tyrosine: A non-essential amino acid. In animals it is synthesized from phenylalanine. It is
Dictionary 323
also the precursor of epinephrine, thyroid hormones, and melanin. [NIH] Ulcer: A localized necrotic lesion of the skin or a mucous surface. [NIH] Ulceration: 1. The formation or development of an ulcer. 2. An ulcer. [EU] Ultrafiltration: The separation of particles from a suspension by passage through a filter with very fine pores. In ultrafiltration the separation is accomplished by convective transport; in dialysis separation relies instead upon differential diffusion. Ultrafiltration occurs naturally and is a laboratory procedure. Artificial ultrafiltration of the blood is referred to as hemofiltration or hemodiafiltration (if combined with hemodialysis). [NIH] Umbilical Arteries: Either of a pair of arteries originating from the internal iliac artery and passing through the umbilical cord to carry blood from the fetus to the placenta. [NIH] Umbilical Cord: The flexible structure, giving passage to the umbilical arteries and vein, which connects the embryo or fetus to the placenta. [NIH] Unconscious: Experience which was once conscious, but was subsequently rejected, as the "personal unconscious". [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. [NIH]
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] Urinary Plasminogen Activator: A proteolytic enzyme that converts plasminogen to plasmin where the preferential cleavage is between arginine and valine. It was isolated originally from human urine, but is found in most tissues of most vertebrates. EC 3.4.21.73. [NIH]
Urinary tract: The organs of the body that produce and discharge urine. These include the kidneys, ureters, bladder, and urethra. [NIH] Urinate: To release urine from the bladder to the outside. [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] Urticaria: A vascular reaction of the skin characterized by erythema and wheal formation due to localized increase of vascular permeability. The causative mechanism may be allergy, infection, or stress. [NIH] Uterus: The small, hollow, pear-shaped organ in a woman's pelvis. This is the organ in which a fetus develops. Also called the womb. [NIH] Vaccine: A substance or group of substances meant to cause the immune system to respond to a tumor or to microorganisms, such as bacteria or viruses. [NIH] Vacuoles: Any spaces or cavities within a cell. They may function in digestion, storage, secretion, or excretion. [NIH] Vagina: The muscular canal extending from the uterus to the exterior of the body. Also called the birth canal. [NIH] Valves: Flap-like structures that control the direction of blood flow through the heart. [NIH]
324 Chondroitin
Vascular: Pertaining to blood vessels or indicative of a copious blood supply. [EU] Vasculitis: Inflammation of a blood vessel. [NIH] Vasoconstriction: Narrowing of the blood vessels without anatomic change, for which constriction, pathologic is used. [NIH] Vasodilator: An agent that widens blood vessels. [NIH] Vasomotor: 1. Affecting the calibre of a vessel, especially of a blood vessel. 2. Any element or agent that effects the calibre of a blood vessel. [EU] Vector: Plasmid or other self-replicating DNA molecule that transfers DNA between cells in nature or in recombinant DNA technology. [NIH] Vein: Vessel-carrying blood from various parts of the body to the heart. [NIH] Venous: Of or pertaining to the veins. [EU] Ventricle: One of the two pumping chambers of the heart. The right ventricle receives oxygen-poor blood from the right atrium and pumps it to the lungs through the pulmonary artery. The left ventricle receives oxygen-rich blood from the left atrium and pumps it to the body through the aorta. [NIH] Ventricular: Pertaining to a ventricle. [EU] Venules: The minute vessels that collect blood from the capillary plexuses and join together to form veins. [NIH] Vertebrae: A bony unit of the segmented spinal column. [NIH] Vertebral: Of or pertaining to a vertebra. [EU] Vertigo: An illusion of movement; a sensation as if the external world were revolving around the patient (objective vertigo) or as if he himself were revolving in space (subjective vertigo). The term is sometimes erroneously used to mean any form of dizziness. [EU] Veterinary Medicine: The medical science concerned with the prevention, diagnosis, and treatment of diseases in animals. [NIH] Vinblastine: An anticancer drug that belongs to the family of plant drugs called vinca alkaloids. It is a mitotic inhibitor. [NIH] Vincristine: An anticancer drug that belongs to the family of plant drugs called vinca alkaloids. [NIH] Viral: Pertaining to, caused by, or of the nature of virus. [EU] Viral Load: The quantity of measurable virus in the blood. Change in viral load, measured in plasma, is used as a surrogate marker in HIV disease progression. [NIH] Virulence: The degree of pathogenicity within a group or species of microorganisms or viruses as indicated by case fatality rates and/or the ability of the organism to invade the tissues of the host. [NIH] Virus: Submicroscopic organism that causes infectious disease. In cancer therapy, some viruses may be made into vaccines that help the body build an immune response to, and kill, tumor cells. [NIH] Visceral: , from viscus a viscus) pertaining to a viscus. [EU] Viscosity: A physical property of fluids that determines the internal resistance to shear forces. [EU] Visual Acuity: Acuteness or clearness of vision, especially of form vision, which is dependent mainly on the sharpness of the retinal focus. [NIH] Visual Cortex: Area of the occipital lobe concerned with vision. [NIH]
Dictionary 325
Vitamin A: A substance used in cancer prevention; it belongs to the family of drugs called retinoids. [NIH] Vitamin E: Vitamin found largely in plant materials, especially wheat germ, corn, sunflower seed, rapeseed, soybean oils, alfalfa, and lettuce. It is used as an antioxidant in vegetable oils and shortenings. [NIH] Vitreous Body: The transparent, semigelatinous substance that fills the cavity behind the crystalline lens of the eye and in front of the retina. It is contained in a thin hyoid membrane and forms about four fifths of the optic globe. [NIH] Vitreous Humor: The transparent, colorless mass of gel that lies behind the lens and in front of the retina and fills the center of the eyeball. [NIH] Vitro: Descriptive of an event or enzyme reaction under experimental investigation occurring outside a living organism. Parts of an organism or microorganism are used together with artificial substrates and/or conditions. [NIH] Vivo: Outside of or removed from the body of a living organism. [NIH] Void: To urinate, empty the bladder. [NIH] Vomeronasal Organ: A specialized part of the olfactory system located anteriorly in the nasal cavity within the nasal septum. Chemosensitive cells of the vomeronasal organ project via the vomeronasal nerve to the accessory olfactory bulb. The primary function of this organ appears to be in sensing pheromones which regulate reproductive and other social behaviors. While the structure has been thought absent in higher primate adults, data now suggests it may be present in adult humans. [NIH] Warts: Benign epidermal proliferations or tumors; some are viral in origin. [NIH] Weight-Bearing: The physical state of supporting an applied load. This often refers to the weight-bearing bones or joints that support the body's weight, especially those in the spine, hip, knee, and foot. [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]
Wound Healing: Restoration of integrity to traumatized tissue. [NIH] Wounds, Gunshot: Disruption of structural continuity of the body as a result of the discharge of firearms. [NIH] Xenograft: The cells of one species transplanted to another species. [NIH] X-ray: High-energy radiation used in low doses to diagnose diseases and in high doses to treat cancer. [NIH] X-ray therapy: The use of high-energy radiation from x-rays to kill cancer cells and shrink tumors. Radiation may come from a machine outside the body (external-beam radiation therapy) or from materials called radioisotopes. Radioisotopes produce radiation and can be placed in or near the tumor or in the area near cancer cells. This type of radiation treatment is called internal radiation therapy, implant radiation, interstitial radiation, or brachytherapy. Systemic radiation therapy uses a radioactive substance, such as a radiolabeled monoclonal antibody, that circulates throughout the body. X-ray therapy is also called radiation therapy, radiotherapy, and irradiation. [NIH] Yeasts: A general term for single-celled rounded fungi that reproduce by budding. Brewers' and bakers' yeasts are Saccharomyces cerevisiae; therapeutic dried yeast is dried yeast. [NIH] Zymogen: Inactive form of an enzyme which can then be converted to the active form, usually by excision of a polypeptide, e. g. trypsinogen is the zymogen of trypsin. [NIH]
326 Chondroitin
327
INDEX A Abdomen, 237, 249, 285, 297, 299, 315, 316, 319 Abdominal, 78, 237, 263, 288, 297, 299, 310 Abdominal Pain, 237, 299 Aberrant, 10, 20, 237 Abrasion, 3, 237 Acceptor, 12, 56, 128, 237, 297, 317, 321 Acetaminophen, 208, 237 Acetylcholine, 237, 239, 255, 294 Acetylgalactosamine, 12, 67, 68, 83, 93, 96, 131, 156, 167, 168, 195, 198, 237 Acetylglucosamine, 27, 41, 56, 157, 198, 237 Acne, 191, 237, 310 Actin, 11, 36, 237, 272, 289, 291 Adaptability, 237, 253, 254 Adaptation, 6, 53, 67, 237, 255, 302 Adenine, 193, 237, 238, 307 Adenosine, 171, 237, 238, 250, 300 Adenosine Diphosphate, 171, 237 Adenosine Triphosphate, 171, 238, 300 Adenovirus, 42, 238 Adhesions, 174, 176, 238, 302 Adjustment, 237, 238 Adjuvant, 238, 272 Adrenal Medulla, 238, 253, 268, 294 Adrenergic, 238, 240, 243, 264, 268, 317 Adsorption, 64, 238, 303 Adverse Effect, 44, 153, 238, 240, 313 Aerosol, 180, 181, 238 Afferent, 25, 238 Affinity, 16, 33, 39, 54, 88, 128, 144, 148, 162, 170, 186, 188, 238, 239, 245, 293, 314 Affinity Chromatography, 39, 144, 148, 238 Agar, 238, 301 Agarose, 144, 238 Age of Onset, 238, 322 Ageing, 60, 239 Aggressiveness, 162, 239 Agonist, 29, 169, 239, 264, 301, 308 Agrin, 185, 239 Albumin, 239, 301, 318 Alertness, 239, 250 Alfalfa, 239, 325 Algorithms, 239, 248 Alimentary, 239, 282, 297, 298
Alkaline, 42, 239, 240, 251 Alkaline Phosphatase, 42, 239 Alkaloid, 239, 245, 251, 257, 290 Alleles, 54, 239 Allylamine, 239, 240 Alpha Particles, 239, 308 Alpha-1, 239, 240 Alternative medicine, 206, 239 Alveolar Process, 240, 310 Amblyopia, 192, 240 Ameliorated, 198, 240 Amine, 144, 240, 276 Amino Acid Sequence, 14, 24, 182, 240, 242, 272, 294, 304, 305 Amino-terminal, 240, 304 Amitriptyline, 202, 240 Ammonia, 240, 323 Ammonium Sulfate, 124, 240 Amyloid, 25, 68, 70, 72, 184, 185, 240 Anabolic, 20, 23, 240 Anaerobic, 101, 114, 118, 240 Anaesthesia, 240, 280 Analgesic, 191, 237, 241, 263, 267, 290 Analogous, 241, 303, 321 Anaphylatoxins, 241, 258 Anatomical, 11, 241, 245, 279, 312 Androgens, 42, 241 Anecdotal report, 169, 199, 241 Anemia, 161, 187, 220, 241, 271, 286, 297 Anesthesia, 241, 261, 266, 304 Anesthetics, 202, 241, 268 Aneuploidy, 10, 241 Anginal, 241, 294 Angiogenesis, 65, 69, 162, 241, 287 Angioplasty, 30, 241 Angiotensinogen, 41, 241, 309, 310 Animal model, 51, 59, 241 Anionic, 16, 242 Anions, 239, 242, 282 Ankle, 60, 77, 242 Anorexia, 242, 297 Antagonism, 242, 250 Antibacterial, 16, 91, 242 Antibiotic, 16, 242, 262, 265 Anticholinergic, 202, 240, 242, 254 Anticoagulant, 29, 50, 57, 105, 242, 263, 306 Anticonvulsant, 242, 252
328 Chondroitin
Antidepressant, 240, 242 Antiemetic, 242, 243, 255, 264, 278 Antigen, 64, 89, 90, 144, 157, 238, 242, 257, 277, 278, 280, 281, 287 Antigen-Antibody Complex, 242, 257 Anti-infective, 242, 251, 271, 314 Anti-Infective Agents, 242, 271 Anti-Inflammatory Agents, 154, 242, 245 Antimicrobial, 91, 164, 242, 263 Antioxidant, 41, 165, 243, 244, 325 Antipruritic, 243, 251 Antipsychotic, 243, 255 Antipyretic, 237, 243, 263 Antiseptic, 177, 243, 319 Antithrombotic, 29, 243, 276, 305 Antitussive, 243, 264 Antiviral, 243, 263, 281, 299 Anxiety, 243, 278 Aorta, 78, 243, 252, 275, 324 Aortic Valve, 38, 243 Apolipoproteins, 243, 285 Aponeurosis, 243, 271 Apoptosis, 28, 43, 59, 243, 253 Applicability, 53, 207, 243 Aqueous, 41, 146, 150, 151, 160, 163, 164, 187, 192, 244, 246, 253, 261, 266, 284 Arachidonate 12-Lipoxygenase, 244, 285 Arachidonate 15-Lipoxygenase, 244, 285 Arachidonate Lipoxygenases, 244, 285 Arachidonic Acid, 155, 244, 284, 305 Arginine, 171, 202, 241, 244, 294, 296, 322, 323 Arterial, 53, 61, 70, 101, 112, 116, 155, 168, 239, 244, 250, 255, 259, 278, 306, 318 Arteries, 61, 146, 158, 183, 243, 244, 245, 249, 260, 275, 285, 288, 307, 320, 323 Arteriolar, 244, 249, 310 Arterioles, 244, 249, 251 Arteriolosclerosis, 244 Arteriosclerosis, 28, 244 Arthralgia, 160, 194, 244 Arthroplasty, 60, 86, 128, 216, 244 Arthroscopy, 216, 217, 244 Ascorbic Acid, 147, 163, 244, 278 Aseptic, 177, 244, 296 Aspartate, 19, 154, 244 Aspirin, 4, 245 Assay, 29, 34, 49, 67, 69, 73, 112, 116, 185, 245 Asthenopia, 194, 245 Astigmatism, 245, 309 Astrocytes, 9, 23, 26, 49, 245, 276, 286, 293
Ataxia, 220, 245, 319 Atherogenic, 51, 54, 61, 245 Atrial, 245, 259, 322 Atrioventricular, 245, 259 Atrium, 245, 252, 259, 319, 322, 324 Atrophy, 189, 220, 245 Atropine, 202, 245, 247 Auditory, 245, 287, 322 Autoimmune disease, 59, 186, 245, 291 Autonomic, 189, 237, 243, 245, 247, 294, 299 Autonomic Nervous System, 245, 247, 299 Autopsy, 60, 246 Autoradiography, 12, 246 Avian, 168, 188, 246 Axonal, 6, 10, 22, 25, 36, 45, 49, 138, 188, 189, 246 Axons, 6, 11, 16, 20, 21, 22, 25, 27, 46, 49, 114, 118, 189, 246, 262, 274, 292, 293, 296 Axotomy, 27, 246 B Bacteria, 16, 145, 238, 242, 246, 247, 254, 258, 269, 270, 275, 276, 288, 289, 309, 313, 321, 323 Bacterial Infections, 50, 246, 254 Bacterial Physiology, 237, 246 Bactericidal, 246, 268 Bacteriophage, 246, 301, 321 Bacterium, 101, 114, 118, 195, 246, 258 Basal cell carcinoma, 85, 246 Basal cells, 246 Basal Ganglia, 243, 245, 246, 249, 271 Basal Ganglia Diseases, 245, 246 Base, 147, 148, 174, 177, 179, 237, 246, 262, 272, 283, 319 Basement Membrane, 7, 10, 72, 100, 124, 246, 269, 284 Basophils, 246, 274, 284 Behavioral Sciences, 8, 246 Belladonna, 245, 247 Benign, 70, 244, 247, 269, 271, 275, 292, 308, 311, 325 Benzocaine, 193, 247 Benzoic Acid, 202, 247 Benzyl Alcohol, 147, 247 Beta-pleated, 240, 247 Beta-sheet, 24, 28, 247 Beta-Thromboglobulin, 247, 281 Bile, 166, 247, 261, 271, 273, 276, 277, 285, 316, 317 Bile Acids, 247, 316, 317 Bile Acids and Salts, 247
Index 329
Bile Ducts, 247, 271 Biliary, 166, 247, 251, 257, 276 Biliary Tract, 166, 247, 251 Bilirubin, 239, 247, 271, 273 Binding agent, 186, 247 Binding Sites, 18, 39, 247 Bioassays, 52, 55, 247 Bioavailability, 99, 115, 118, 129, 153, 247 Bioavailable, 101, 247 Biochemical Phenomena, 248 Biodegradation, 114, 117, 248 Biological Phenomena, 162, 248 Biological response modifier, 248, 281 Biological therapy, 248, 274 Biological Transport, 248, 263 Biomarkers, 19, 248 Biomechanics, 31, 248 Biophysics, 46, 77, 79, 97, 248 Biopsy, 248, 299 Biosynthesis, 26, 47, 51, 71, 88, 93, 125, 128, 244, 248, 305, 313 Biotechnology, 25, 51, 61, 64, 206, 215, 216, 219, 220, 221, 248 Biotin, 248, 295 Biotransformation, 248 Bladder, 65, 171, 202, 248, 261, 282, 291, 293, 298, 305, 310, 323, 325 Blastocyst, 249, 258, 301 Blood Coagulation, 50, 249, 251, 320 Blood Coagulation Factors, 249 Blood Glucose, 249, 275, 281 Blood Platelets, 249, 302, 313, 319 Blood pressure, 249, 252, 278, 290, 294, 307, 314 Blot, 19, 27, 34, 249, 295 Body Fluids, 19, 149, 248, 249, 250, 265, 314, 322 Bone Marrow, 59, 249, 286, 315, 316 Bone Resorption, 149, 249 Boron, 120, 161, 249 Boron Neutron Capture Therapy, 249 Bowel, 249, 264, 284, 299 Bowel Movement, 249, 264 Brachytherapy, 249, 282, 283, 308, 325 Bradykinin, 249, 294, 301 Brain Hypoxia, 249, 250, 319 Brain Infarction, 249, 250 Brain Ischemia, 59, 250 Branch, 233, 250, 266, 286, 287, 298, 307, 315, 319 Breakdown, 53, 58, 169, 199, 250, 263, 272, 296
Breeding, 42, 250 Bronchi, 250, 268, 321 Bronchial, 250, 276 Buccal, 250, 276, 278, 285 Bupivacaine, 250, 284 Burns, 167, 196, 250, 277 Burns, Electric, 250 Bursitis, 155, 250 Bypass, 43, 250 C Cadherins, 17, 250 Caffeine, 169, 250, 307 Calcification, 125, 128, 168, 244, 250 Calcineurin, 34, 37, 250 Calcium channel blocker, 202, 251 Calcium Channel Blockers, 202, 251 Calcium Compounds, 152, 251 Calcium Hydroxide, 152, 251 Calculi, 251, 274 Callus, 59, 251, 266 Calmodulin, 34, 250, 251, 280 Camphor, 66, 124, 251 Cannula, 185, 251 Capillary, 103, 109, 167, 170, 249, 251, 253, 311, 324 Capillary Fragility, 251, 253, 311 Capillary Permeability, 170, 249, 251 Capsaicin, 217, 251 Capsular, 16, 44, 91, 182, 251 Capsules, 91, 198, 252, 265, 272 Carbamazepine, 202, 252 Carbohydrate Sequence, 16, 252 Carbon Dioxide, 251, 252, 262, 301, 310 Carboxy, 181, 252 Carcinogenic, 252, 280, 296, 304, 316, 322 Carcinogens, 252, 291, 296 Carcinoma, 10, 43, 88, 99, 100, 252 Cardiac, 30, 38, 150, 239, 250, 252, 260, 268, 275, 284, 291, 311, 316 Cardiopulmonary, 29, 252 Cardiopulmonary Bypass, 29, 252 Cardiovascular, 38, 54, 168, 252, 284, 313 Cardiovascular disease, 54, 252 Carotene, 252, 310 Carotenoids, 160, 252 Carrier Proteins, 252, 301 Case report, 62, 128, 217, 252, 256 Case series, 252, 256 Caspase, 43, 253 Castor Oil, 193, 253 Catabolism, 3, 19, 49, 253 Cataract, 25, 251, 253
330 Chondroitin
Catechin, 165, 253 Catecholamine, 253, 264, 300 Cathepsins, 15, 253 Catheterization, 241, 253 Catheters, 155, 253, 279, 282 Cations, 253, 282 Caudal, 253, 263, 303 Causal, 253, 276, 302 Cause of Death, 166, 253 Cell Adhesion, 14, 39, 42, 67, 72, 78, 99, 174, 184, 186, 250, 253, 281 Cell Adhesion Molecules, 14, 253 Cell Cycle, 21, 253, 256 Cell Death, 59, 185, 243, 253, 292 Cell Differentiation, 148, 186, 253, 313 Cell Division, 219, 246, 253, 254, 259, 274, 287, 289, 301, 305, 312 Cell membrane, 5, 9, 248, 251, 252, 254, 262, 272, 280, 300 Cell motility, 162, 254, 276 Cell Movement, 15, 162, 254 Cell proliferation, 18, 24, 145, 146, 168, 174, 186, 244, 254, 313 Cell Survival, 254, 274, 275 Cell Transplantation, 5, 45, 254 Cellobiose, 254 Cellular Structures, 254, 290 Cellulose, 144, 180, 193, 254, 301 Cerebellar, 245, 254, 309 Cerebral, 39, 185, 245, 246, 249, 254, 268, 269, 286, 292, 295, 307, 318 Cerebral hemispheres, 246, 249, 254, 318 Cerebrovascular, 246, 251, 252, 254, 319 Cerebrum, 254, 318, 322 Cervix, 81, 254 Cetirizine, 254, 278 Chaperonins, 254, 289 Character, 254, 262 Chelation, 7, 255 Chemokines, 59, 100, 255 Chemotactic Factors, 255, 258 Chemotaxis, 35, 255 Chemotherapy, 255, 279 Chimeras, 18, 255 Chlorpromazine, 193, 255 Cholesterol, 133, 247, 255, 256, 260, 271, 285, 308, 316 Cholesterol Esters, 255, 285 Cholinergic, 240, 243, 255 Chondrogenesis, 21, 42, 60, 255 Chondroitin Lyases, 79, 113, 117, 130, 255 Choroid, 158, 183, 255, 310
Chromatin, 243, 255 Chromosomal, 77, 89, 97, 241, 255 Chromosome, 10, 241, 255, 258, 275, 285, 290, 312, 322 Chronic renal, 255, 303 Chylomicrons, 256, 285 Ciliary, 256, 313 Ciliary Body, 256, 313 Cimetidine, 202, 256 CIS, 256, 310 Cisplatin, 98, 99, 115, 118, 256 Citric Acid, 190, 193, 256 Citrus, 244, 256 Clamp, 25, 256 Clear cell carcinoma, 256, 263 Clinical Medicine, 256, 304 Clinical study, 74, 256, 259 Clinical trial, 5, 24, 66, 139, 140, 169, 199, 210, 215, 256, 259, 265, 306, 308 Clone, 12, 26, 29, 52, 158, 256 Cloning, 8, 14, 40, 56, 63, 76, 77, 89, 95, 96, 97, 148, 248, 256, 280 Clot Retraction, 256, 301 Coagulation, 26, 50, 249, 256, 276, 301, 320 Coenzyme, 160, 244, 257 Cofactor, 26, 28, 29, 35, 257, 294, 306, 320 Colchicine, 257, 322 Collagen disease, 257, 312 Collagenases, 15, 58, 60, 257 Collapse, 11, 176, 250, 257 Colloidal, 75, 113, 187, 239, 257, 266 Combination Therapy, 172, 257, 268 Common Bile Duct, 166, 257, 261 Communis, 253, 257 Complement, 5, 29, 35, 62, 89, 103, 156, 157, 241, 257, 258, 272, 281, 301 Complement Activation, 5, 29, 157, 241, 258 Complementary and alternative medicine, 123, 124, 135, 258 Complementary medicine, 124, 258 Computational Biology, 215, 219, 258 Concentric, 88, 244, 258 Conception, 258, 259, 270 Concomitant, 43, 192, 258 Cone, 11, 13, 17, 25, 36, 98, 113, 258, 300, 317 Conjugated, 37, 144, 167, 247, 258, 261 Conjugation, 248, 258, 317 Conjunctiva, 258, 312 Connective Tissue Cells, 259 Connective Tissue Diseases, 197, 259
Index 331
Connexins, 259, 272 Consciousness, 241, 259, 264 Constipation, 194, 243, 259, 299 Consultation, 8, 259 Consumption, 159, 179, 259, 263, 310 Contact Inhibition, 10, 259 Contraception, 162, 259 Contraceptive, 55, 259 Contracture, 91, 259 Contraindications, ii, 259 Control group, 44, 259 Controlled clinical trial, 207, 259 Controlled study, 44, 259 Coordination, 259, 291 Cor, 40, 105, 151, 259, 305 Cornea, 40, 47, 245, 260, 273, 283, 311, 316 Corneal Stroma, 40, 260 Corneal Transplantation, 151, 192, 260 Corneal Ulcer, 167, 260 Corneum, 165, 260, 268, 278 Coronary, 252, 260, 288 Coronary heart disease, 252, 260 Coronary Thrombosis, 260, 288 Corpuscle, 260, 268 Cortex, 25, 240, 245, 260, 267, 269, 292, 304, 309, 310 Cortical, 25, 79, 240, 260, 312, 319 Corticosteroids, 217, 260, 312 Cranial, 260, 269, 275, 293, 296, 299 Creatine, 170, 171, 191, 260 Creatinine, 164, 191, 260 Cribriform, 260, 295 Cromolyn Sodium, 171, 202, 260 Crossing-over, 260, 309 Cryofixation, 261 Cryopreservation, 196, 261 Cues, 11, 17, 20, 21, 36, 57, 261 Cultured cells, 61, 70, 261 Curare, 261, 291 Curative, 31, 261, 319 Cutaneous, 20, 261, 278, 283, 285 Cyanide, 261, 288 Cyclic, 11, 34, 250, 251, 261, 274, 294, 305 Cysteine, 15, 25, 107, 165, 255, 261, 267, 317 Cystic Duct, 257, 261 Cystine, 261 Cystitis, 65, 107, 109, 115, 119, 171, 202, 261 Cytochrome, 256, 261 Cytokine, 18, 32, 39, 52, 261, 281
Cytoplasm, 243, 246, 254, 261, 262, 267, 274, 280, 311 Cytoskeletal Proteins, 6, 261 Cytoskeleton, 11, 261, 262, 281, 289 Cytotoxic, 98, 251, 262, 279, 308, 314 Cytotoxicity, 239, 256, 262, 283 D Databases, Bibliographic, 215, 262 Daunorubicin, 262, 265 Deamination, 262, 323 Decarboxylation, 262, 276 Decidua, 262, 301 Decubitus, 167, 196, 262, 314 Decubitus Ulcer, 167, 262, 314 Defense Mechanisms, 30, 50, 262, 281 Degenerative, 23, 52, 60, 87, 109, 132, 145, 147, 151, 154, 160, 173, 178, 262, 296, 311 Deletion, 8, 17, 26, 243, 262 Denaturation, 60, 262 Dendrites, 262, 274, 293, 295 Dendritic, 21, 262, 287 Density, 8, 34, 45, 71, 77, 88, 92, 106, 107, 168, 196, 262, 285, 296, 303 Dental implant, 80, 262 Dentate Gyrus, 262, 276 Depolarization, 262, 314 Deprivation, 240, 263 Dermal, 8, 167, 196, 263 Dermatitis, 263, 265, 278 DES, 35, 148, 241, 263 Detergents, 263, 314 Deuterium, 263, 277 Developed Countries, 263, 271 Dextran Sulfate, 170, 179, 263 Diabetes Mellitus, 263, 276 Diagnostic procedure, 143, 206, 263 Dialysis Solutions, 164, 263 Diamines, 77, 93, 263 Diaphragm, 263, 276, 302 Diarrhoea, 263, 278 Diastolic, 263, 278 Diclofenac, 78, 195, 263 Diclofenac Sodium, 78, 195, 263 Diencephalon, 263, 305, 318 Diffusion, 31, 164, 193, 248, 251, 263, 274, 323 Diffusivity, 5, 46, 263 Digestion, 19, 127, 132, 239, 247, 249, 263, 285, 316, 323 Digestive system, 140, 264, 290 Digestive tract, 264, 314, 316 Dilatation, 78, 241, 264, 304
332 Chondroitin
Dimethyl, 171, 264 Dipeptides, 191, 264 Diphenhydramine, 199, 264 Diploid, 241, 264, 290, 301, 322 Direct, iii, 13, 18, 24, 30, 31, 36, 39, 46, 47, 53, 166, 256, 264, 285, 309, 318 Disaccharides, 30, 57, 68, 109, 124, 186, 195, 198, 264 Disease Progression, 59, 264, 324 Disinfectant, 264, 268 Dissection, 81, 264 Dissociation, 7, 33, 238, 264 Dissociative Disorders, 264 Distal, 36, 154, 155, 189, 246, 264, 299, 306 Diuresis, 250, 264 Diuretic, 264, 315 Domesticated, 176, 264 Dopamine, 34, 243, 255, 264, 300 Dorsal, 20, 27, 46, 265, 293, 303, 315 Dorsum, 265, 271 Dosage Forms, 177, 265, 299 Dose-limiting, 42, 265 Double-blinded, 44, 107, 132, 265 Doxorubicin, 171, 265 Drive, ii, vi, 43, 111, 265, 284 Drug Interactions, 265 Duct, 105, 166, 251, 253, 257, 265, 311 Duodenum, 247, 265, 316 Dura mater, 265, 287, 297 Dyes, 240, 246, 265, 271, 275, 299, 317 Dyspareunia, 265, 268 Dysplasia, 155, 220, 265 Dyspnea, 265, 302, 307 Dystrophic, 7, 185, 196, 265, 268 Dystrophy, 40, 68, 220, 265 E Echinacea, 155, 265 Ectoderm, 265, 293 Eczema, 191, 265 Effector, 35, 36, 237, 257, 265, 283, 294 Effusion, 176, 177, 266, 302, 318 Elasticity, 54, 244, 266, 314 Elastin, 38, 170, 188, 257, 259, 266, 269, 284 Electrocoagulation, 257, 266 Electrolyte, 146, 192, 266, 275, 314, 315 Electrons, 243, 246, 266, 282, 297, 308 Electrophoresis, 80, 95, 103, 109, 113, 117, 149, 266 Electrophysiological, 34, 55, 266 Electroplating, 266, 317 Embryo, 36, 126, 130, 249, 253, 265, 266, 280, 288, 297, 303, 323
Embryogenesis, 162, 266 Emollient, 266, 295 Empirical, 171, 266 Emulsion, 246, 266 Encapsulated, 5, 266 Encephalopathy, 169, 188, 194, 266 Endarterectomy, 241, 266 Endemic, 17, 266, 286, 315 Endocytosis, 87, 184, 267 Endopeptidases, 253, 267, 306 Endorphin, 267, 271 Endothelial cell, 39, 51, 56, 61, 72, 75, 84, 87, 113, 146, 151, 167, 189, 267, 270, 281, 319 Endothelium, 267, 294, 301 Endothelium-derived, 267, 294 Endotoxins, 258, 267, 283 End-stage renal, 255, 267, 303 Enhancer, 193, 267 Enteropeptidase, 267, 322 Entorhinal Cortex, 267, 276 Environmental Exposure, 267, 296 Environmental Health, 214, 216, 267 Enzymatic, 22, 76, 83, 127, 146, 148, 173, 217, 251, 252, 258, 267, 276, 310 Enzyme Inhibitors, 26, 267, 301 Eosinophil, 267, 309 Epidermal, 8, 18, 165, 196, 267, 283, 287, 325 Epidermal Growth Factor, 18, 267 Epidermis, 20, 165, 246, 260, 267, 268, 277, 278, 283, 304, 307 Epidermoid carcinoma, 268, 316 Epidermolysis Bullosa, 7, 196, 268 Epinephrine, 164, 238, 264, 268, 294, 323 Epiphyseal, 128, 268 Epiphyses, 126, 268 Episcleritis, 268, 311 Epithelial, 14, 41, 102, 151, 156, 166, 167, 248, 256, 260, 262, 267, 268, 276, 284 Epithelial Cells, 41, 151, 166, 167, 267, 268, 276, 284 Epithelium, 10, 246, 267, 268, 282 Epitope, 11, 56, 66, 67, 89, 90, 112, 116, 124, 132, 268 Erythrocyte Membrane, 62, 63, 90, 106, 110, 268 Esophagus, 264, 268, 316 Essential Tremor, 220, 268 Estrogen, 23, 268, 308, 312 Estrogen receptor, 23, 268 Estrogen Replacement Therapy, 23, 268
Index 333
Ethanol, 147, 197, 268 Ethmoid, 269, 295 Eukaryotic Cells, 261, 269, 279, 295, 296 Evacuation, 259, 269, 284 Evoke, 22, 269, 316 Excipient, 269, 274, 321 Excrete, 100, 164, 269 Exhaustion, 242, 269, 286 Exogenous, 23, 42, 47, 238, 248, 265, 269, 273, 306, 317, 322 Exostoses, 43, 269 Extensor, 269, 307 External-beam radiation, 269, 283, 308, 325 Extracellular Matrix Proteins, 6, 33, 269, 287 Extracellular Space, 269 Extracorporeal, 29, 269, 275 Extraction, 195, 269 Extrapyramidal, 243, 264, 269 Exudate, 177, 269, 274, 302, 321 Eye Infections, 164, 238, 269 F Family Planning, 215, 269 Fat, 244, 247, 249, 252, 259, 260, 262, 270, 285, 291, 295, 311, 315, 317, 318 Fatigue, 161, 245, 270, 275 Fatty acids, 208, 239, 270, 285, 305, 314, 320 Feces, 259, 270 Femoral, 155, 252, 270 Femoral Artery, 252, 270 Femur, 36, 270 Fertilizers, 270, 317 Fetus, 270, 301, 304, 323 Fibril, 40, 46, 47, 53, 270 Fibrin, 29, 249, 256, 270, 299, 301, 302, 319, 320 Fibrinogen, 270, 301, 319 Fibroblast Growth Factor, 57, 65, 270 Fibroblasts, 10, 15, 19, 40, 42, 43, 92, 93, 167, 195, 196, 259, 270, 281 Fibronectin, 36, 39, 43, 46, 57, 78, 84, 93, 167, 186, 188, 270, 272 Fibrosis, 81, 105, 164, 166, 175, 220, 239, 259, 270, 307, 312 Fibrotic tissue, 174, 270 Flatus, 270, 272 Flavoring Agents, 270, 271, 299 Flexor, 269, 270, 319 Fluorescence, 28, 46, 109, 270 Folate, 270, 271
Fold, 6, 25, 28, 29, 271 Folic Acid, 172, 271 Food Additives, 152, 197, 198, 271 Food Coloring Agents, 271 Food Preservatives, 271 Foramen, 257, 271, 287, 299 Fractionation, 124, 240, 271 Friction, 155, 161, 197, 209, 271 Fucose, 105, 271 Fungi, 258, 269, 271, 274, 288, 289, 325 Fungistatic, 247, 271 G Gait, 44, 271 Gallbladder, 237, 247, 261, 264, 271 Gallstones, 166, 247, 271 Gamma irradiation, 38, 271 Gamma-Endorphin, 271 Ganglia, 20, 189, 237, 246, 271, 293, 299 Ganglion, 16, 46, 271, 293, 296 Gap Junctions, 9, 259, 271, 318 Gas, 225, 240, 252, 263, 270, 272, 277, 291, 294 Gastric, 256, 265, 267, 272, 276, 298 Gastric Acid, 256, 272 Gastrin, 256, 272, 277 Gastrointestinal, 166, 169, 182, 209, 249, 268, 272, 284, 286, 298, 313, 317, 322 Gastrointestinal tract, 169, 182, 268, 272, 284, 298, 313, 322 Gelatin, 85, 91, 272, 273, 317, 319 Gelatinase A, 33, 272 Gelatinases, 34, 272 Gels, 19, 37, 38, 77, 93, 272 Gelsolin, 37, 272 Gene, 8, 10, 21, 23, 26, 29, 30, 32, 34, 40, 41, 42, 47, 54, 61, 62, 66, 77, 84, 85, 89, 97, 103, 156, 158, 166, 221, 222, 238, 239, 248, 259, 272, 280, 285, 295, 302, 312, 321 Gene Expression, 34, 43, 54, 61, 221, 272 Generator, 170, 272 Genetic Code, 272, 295 Genetic Engineering, 248, 256, 272 Genetic Screening, 48, 272 Genetics, 15, 258, 272, 290 Genotype, 59, 273, 300 Germ Cells, 273, 287, 315, 319 Gestation, 273, 301 Gland, 238, 273, 276, 285, 297, 301, 305, 308, 312, 316, 317, 320 Glomerular, 21, 41, 273, 282 Glomeruli, 21, 42, 273, 295 Glomerulus, 273, 292
334 Chondroitin
Glucose, 5, 30, 101, 193, 220, 244, 249, 254, 263, 273, 275, 280, 281, 311, 315 Glucuronate, 255, 273 Glucuronic Acid, 12, 26, 83, 96, 131, 153, 160, 175, 182, 195, 198, 273, 276, 279 Glucuronides, 273 Glutamic Acid, 271, 273, 304 Glutathione Peroxidase, 273, 312 Glycine, 171, 182, 247, 273, 313 Glycogen, 147, 273 Glycoprotein, 15, 114, 117, 166, 270, 273, 274, 284, 319 Glycoside, 264, 273, 311 Glycosidic, 175, 254, 273, 295 Glycosylation, 49, 273 Gonad, 274 Gonadal, 9, 274, 316 Gout, 155, 257, 274 Governing Board, 274, 304 Gp120, 274, 299 Grade, 77, 274 Graft, 5, 274, 277 Graft Survival, 5, 274 Grafting, 181, 274, 279 Granule, 262, 274, 311 Granulocytes, 274, 314, 325 Grasses, 271, 274 Gravidity, 62, 87, 274, 298 Growth Cones, 13, 17, 25, 36, 46, 84, 98, 274 Growth factors, 8, 14, 15, 26, 42, 104, 145, 146, 170, 173, 188, 196, 203, 274, 293 Growth Plate, 48, 274 Guanylate Cyclase, 274, 294 Gum Arabic, 180, 274 H Haemodialysis, 84, 274 Hair Color, 275 Hair Dyes, 181, 275 Half-Life, 157, 275 Haploid, 275, 301 Haptens, 238, 275 Headache, 250, 275 Health Promotion, 8, 275 Heart attack, 252, 275 Heart failure, 275, 307 Heart Valves, 38, 275 Heat-Shock Proteins, 275, 289 Heat-Shock Proteins 90, 275, 289 Hematogenous, 59, 275 Hematology, 26, 275 Hematopoietic Stem Cells, 55, 275
Hemodiafiltration, 275, 323 Hemodialysis, 275, 323 Hemofiltration, 275, 323 Hemoglobin, 106, 107, 132, 241, 268, 275, 276, 284 Hemoglobinuria, 220, 276 Hemolysis, 268, 276 Hemorrhage, 158, 183, 266, 275, 276, 307, 316 Hemostasis, 276, 281, 313 Heparan Sulfate Proteoglycan, 15, 42, 61, 90, 276 Hepatic, 166, 239, 257, 276 Hepatobiliary, 166, 276 Hepatocyte, 83, 276 Hepatocyte Growth Factor, 83, 276 Hereditary, 259, 274, 276, 301, 310 Heredity, 272, 273, 276 Heterodimers, 276, 281, 321 Heterogeneity, 88, 106, 124, 128, 238, 276 Hiccup, 255, 276 Hippocampus, 33, 59, 262, 276, 317 Hirudin, 28, 29, 276 Histamine, 169, 241, 243, 254, 256, 264, 276, 277, 278 Histidine, 276, 277 Histology, 26, 277 Homeostasis, 23, 27, 277 Homodimer, 277, 321 Homogeneous, 188, 244, 277, 300 Homologous, 7, 56, 76, 239, 259, 261, 272, 277, 312, 318 Hormonal, 23, 245, 268, 277 Horny layer, 268, 277 Host, 50, 63, 156, 157, 178, 246, 270, 274, 277, 284, 324 Humoral, 32, 277 Humour, 176, 277 Hyaluronidase, 71, 115, 119, 130, 132, 146, 147, 158, 183, 277 Hybrid, 7, 48, 57, 256, 277, 295 Hybridization, 175, 277, 290, 295 Hydration, 162, 277 Hydrofluoric Acid, 277, 314 Hydrogel, 177, 193, 277 Hydrogen, 160, 237, 240, 246, 252, 262, 263, 269, 273, 277, 278, 289, 290, 294, 295, 297, 306 Hydrolysis, 248, 254, 256, 277, 284, 285, 298, 300, 303, 306, 322 Hydrophilic, 154, 263, 277, 303 Hydrophobic, 25, 187, 263, 277, 285
Index 335
Hydroxylation, 170, 278 Hydroxylysine, 182, 257, 278 Hydroxyproline, 182, 191, 257, 278 Hydroxyzine, 202, 278 Hygienic, 278, 314 Hyperkeratosis, 191, 278 Hyperopia, 278, 309 Hyperplasia, 70, 278 Hypersensitivity, 264, 267, 278, 284, 311 Hypertension, 152, 166, 244, 251, 252, 275, 278, 320 Hypertrophy, 59, 60, 260, 269, 278, 322 Hyperuricemia, 274, 278 Hypervitaminosis, 127, 278 Hypesthesia, 278, 293 Hypnotic, 264, 278 Hypoplasia, 14, 278 Hypotensive, 147, 278 Hypothermia, 194, 278 I Ichthyosis, 191, 278 Id, 120, 133, 226, 232, 234, 278 Idiopathic, 9, 279 Iduronic Acid, 26, 29, 148, 160, 181, 198, 279 Immaturity, 14, 279 Immune function, 279, 321 Immune response, 16, 17, 162, 186, 190, 238, 242, 245, 275, 279, 312, 317, 324 Immune system, 186, 248, 279, 284, 286, 291, 323, 325 Immunity, 17, 32, 75, 79, 80, 83, 87, 90, 92, 98, 219, 279, 295 Immunocompromised, 37, 279 Immunoconjugates, 62, 89, 279 Immunodeficiency, 220, 279 Immunogenic, 126, 279 Immunoglobulin, 98, 242, 279, 290 Immunohistochemistry, 5, 22, 34, 51, 279 Immunology, 64, 74, 89, 92, 100, 103, 104, 125, 128, 157, 186, 238, 279 Immunophilin, 251, 279 Immunosuppressive, 251, 279, 312 Immunosuppressive Agents, 279, 312 Impairment, 165, 193, 245, 269, 279, 288 Implant radiation, 279, 282, 283, 308, 325 Implantation, 38, 151, 258, 279 In situ, 5, 10, 14, 20, 22, 34, 60, 85, 279 In Situ Hybridization, 14, 20, 22, 34, 60, 85, 279 Incision, 280, 282, 305, 310 Incubation, 107, 184, 280
Indicative, 162, 201, 280, 298, 324 Induction, 11, 21, 52, 60, 168, 186, 241, 243, 280 Infarction, 247, 249, 260, 280, 288 Infuse, 185, 280 Ingestion, 152, 163, 278, 280, 302 Inhalation, 238, 276, 280, 302 Initiation, 10, 11, 80, 83, 96, 97, 280, 321 Inlay, 280, 310 Innervation, 20, 280 Inorganic, 178, 251, 256, 280, 290, 317 Inositol, 34, 280 Inositol 1,4,5-Trisphosphate, 34, 280 Inotropic, 265, 280 Insertional, 21, 280 Insight, 25, 26, 39, 53, 281 Instillation, 172, 281 Insulator, 281, 291 Insulin, 101, 281, 283, 322 Insulin-dependent diabetes mellitus, 281 Integrins, 6, 17, 281 Interferon, 71, 92, 281 Interferon-alpha, 281 Interleukin-1, 23, 27, 52, 81, 281 Interleukin-2, 281 Interleukin-8, 71, 281 Intermittent, 52, 281, 299 Internal Medicine, 105, 107, 131, 132, 216, 275, 281, 311 Internal radiation, 282, 283, 308, 325 Interstitial, 15, 65, 85, 99, 107, 109, 115, 119, 171, 202, 249, 269, 272, 282, 283, 292, 325 Interstitial Collagenase, 85, 272, 282 Intervertebral, 69, 102, 282 Intestinal, 10, 101, 114, 118, 169, 199, 225, 252, 267, 282, 286 Intestines, 237, 270, 272, 282 Intrahepatic, 166, 282 Intramuscular, 147, 282, 297 Intraocular, 151, 192, 282 Intraocular pressure, 192, 282 Intravascular, 50, 155, 282 Intravenous, 187, 282, 297 Intravesical, 171, 282 Intrinsic, 6, 129, 191, 238, 246, 282 Inulin, 265, 282 Invasive, 37, 43, 162, 202, 279, 282, 286 Involuntary, 246, 268, 282, 291, 314 Ion Channels, 245, 282, 293, 294 Ion Exchange, 146, 148, 254, 282
336 Chondroitin
Ions, 164, 188, 246, 251, 264, 266, 272, 277, 280, 282, 290, 306 Iris, 260, 282, 307 Irradiation, 41, 249, 282, 310, 325 Irritants, 171, 283 Ischemia, 245, 250, 262, 283 Islet, 5, 283 J Joint, 3, 11, 23, 36, 41, 44, 52, 60, 66, 74, 76, 85, 87, 93, 94, 104, 109, 114, 117, 132, 145, 147, 153, 154, 155, 161, 163, 169, 172, 173, 176, 177, 178, 179, 180, 194, 197, 203, 208, 217, 244, 270, 283, 296, 318 Joint Capsule, 44, 283, 318 K Karaya Gum, 180, 283 Kb, 214, 283 Keratan Sulfate, 28, 40, 56, 68, 91, 148, 150, 157, 162, 168, 179, 185, 186, 283 Keratin, 283 Keratinocytes, 8, 43, 77, 93, 195, 196, 281, 283 Keto, 191, 283 Kidney Disease, 140, 214, 220, 283 Killer Cells, 283 Kinetic, 15, 283 L Labile, 257, 283 Laminin, 21, 46, 73, 76, 84, 101, 112, 116, 167, 186, 188, 246, 269, 284 Large Intestine, 264, 282, 284, 309, 314 Larynx, 90, 161, 284, 321 Latent, 22, 284 Laxative, 238, 283, 284, 315, 321 Lectin, 14, 56, 63, 107, 284, 287 Lens, 25, 151, 158, 183, 251, 253, 284, 325 Lesion, 27, 33, 51, 284, 285, 313, 323 Lethal, 21, 39, 166, 246, 261, 284, 291 Leucine, 18, 53, 188, 284, 298 Leukemia, 73, 168, 219, 265, 284 Leukocyte Elastase, 92, 284 Leukocytes, 35, 56, 74, 113, 117, 125, 246, 249, 255, 274, 281, 284 Leukotrienes, 156, 244, 284 Libido, 241, 284 Library Services, 232, 284 Lidocaine, 171, 193, 247, 284 Ligament, 284, 305 Ligands, 39, 40, 56, 89, 128, 253, 281, 285 Linkage, 12, 40, 68, 70, 93, 97, 110, 126, 129, 131, 175, 254, 285
Lipid, 5, 101, 243, 244, 251, 281, 283, 285, 291 Lipoprotein, 54, 61, 70, 71, 77, 88, 106, 112, 116, 149, 285 Liposomes, 99, 101, 285 Lipoxygenase, 156, 244, 284, 285 Liver, 99, 166, 184, 237, 239, 244, 247, 248, 264, 266, 270, 271, 273, 276, 282, 285, 310, 323 Localization, 10, 15, 18, 22, 36, 48, 89, 90, 94, 102, 114, 117, 157, 279, 285, 292 Localized, 9, 31, 36, 57, 59, 146, 166, 250, 261, 266, 280, 284, 285, 301, 312, 323 Locomotion, 259, 285, 301 Loop, 28, 53, 285 Low-density lipoprotein, 51, 92, 94, 285 Lucida, 284, 285 Lumbar, 69, 285 Lumen, 7, 251, 285 Lupus, 155, 257, 285 Lyases, 52, 57, 101, 109, 114, 118, 285 Lymph, 56, 260, 267, 277, 285, 286, 302, 317 Lymph node, 56, 285, 286 Lymphatic, 184, 267, 280, 285, 286, 288, 315, 320 Lymphatic system, 184, 285, 286, 315, 320 Lymphocyte, 56, 242, 283, 286, 287 Lymphoid, 56, 242, 260, 286, 320 Lymphoma, 219, 286 Lysine, 278, 286, 304, 322 M Macroglia, 27, 286, 293 Macrophage, 5, 94, 107, 168, 281, 286 Magnetic Resonance Imaging, 51, 88, 286 Malabsorption, 220, 286 Malaise, 81, 161, 286 Malaria, 17, 32, 39, 63, 68, 92, 94, 98, 100, 103, 286, 301, 302 Malaria, Falciparum, 286 Malaria, Vivax, 286 Malignant, 37, 43, 64, 103, 108, 219, 244, 286, 292, 308, 311, 319 Malignant tumor, 64, 286 Malnutrition, 239, 245, 286, 291 Mammary, 286, 308 Mammogram, 250, 286, 288 Mandible, 240, 286, 310 Manifest, 42, 246, 287 Matrix metalloproteinase, 22, 23, 36, 37, 41, 48, 58, 85, 94, 95, 158, 183, 287 Meatus, 287, 322
Index 337
Medial, 244, 269, 287 Mediate, 6, 14, 34, 39, 59, 62, 72, 73, 89, 99, 253, 264, 283, 287, 289 Mediator, 23, 34, 50, 281, 287, 302, 313 Medical Staff, 265, 287 Medicament, 164, 192, 287, 317 MEDLINE, 215, 219, 220, 287 Megaloblastic, 271, 287 Meiosis, 287, 318 Melanin, 282, 287, 300, 323 Melanocytes, 287 Melanoma, 37, 39, 62, 63, 66, 67, 72, 89, 90, 94, 95, 97, 101, 112, 116, 219, 249, 287 Membrane Proteins, 285, 287 Meninges, 254, 265, 287 Meningitis, 16, 287 Menopause, 287, 303 Mental Disorders, 141, 288 Mental Health, iv, 4, 141, 214, 218, 288, 307 Mental Processes, 264, 288, 307 Mental Retardation, 9, 221, 288 Menthol, 178, 288 Mesenchymal, 22, 42, 59, 102, 267, 288 Mesentery, 288, 299 Mesoderm, 9, 288 Mesothelial, 164, 288 Meta-Analysis, 86, 105, 127, 131, 169, 199, 288 Metabolic disorder, 274, 288 Metabolite, 248, 264, 278, 288, 304 Metaplasia, 91, 288 Metastasis, 38, 39, 99, 186, 253, 287, 288 Methionine, 165, 171, 264, 288, 305, 317 Methylene Blue, 202, 288 MI, 102, 235, 288 Microbe, 288, 321 Microbiology, 71, 102, 109, 112, 116, 237, 288 Microcalcifications, 250, 288 Microfibrils, 84, 288 Microfilaments, 12, 289 Microorganism, 257, 289, 298, 325 Microscopy, 9, 11, 27, 46, 51, 90, 98, 185, 246, 289, 295, 303 Microspheres, 85, 289, 303 Microtubules, 36, 289 Migration, 7, 9, 18, 23, 25, 36, 43, 61, 72, 103, 162, 167, 174, 289, 293 Mineralization, 48, 251, 289, 297 Miotic, 289, 301 Mitochondria, 254, 289, 296
Mitosis, 243, 289 Mobility, 28, 145, 176, 195, 289 Mobilization, 12, 289 Modeling, 16, 95, 289 Models, Chemical, 203, 289 Modification, 41, 44, 46, 51, 67, 76, 106, 207, 272, 289, 307 Modulator, 23, 289 Molecular Chaperones, 6, 254, 275, 289 Molecular mass, 92, 289 Molecular Probes, 162, 290 Molecular Structure, 6, 290 Monitor, 209, 260, 290, 294 Monoclonal, 11, 14, 16, 25, 56, 66, 90, 102, 103, 124, 279, 283, 290, 308, 325 Monoclonal antibodies, 11, 14, 25, 56, 102, 103, 279, 290 Monocyte, 80, 290 Monosomy, 241, 290 Monotherapy, 172, 290 Morphine, 290, 292 Morphogenesis, 9, 14, 184, 290 Morphological, 47, 55, 81, 239, 266, 287, 290 Morphology, 34, 36, 98, 115, 119, 167, 253, 275, 290 Motility, 72, 176, 272, 290, 313 Motor nerve, 290, 291 Motor Neurons, 189, 290 Mucinous, 271, 290 Mucins, 290, 311 Mucosa, 285, 290 Mucosal Lining, 172, 290 Mucositis, 290, 320 Mucus, 166, 290 Multiple sclerosis, 59, 110, 115, 119, 291 Muscle Contraction, 171, 291 Muscle Fibers, 239, 291 Muscle relaxant, 202, 291 Muscle tension, 209, 291 Muscular Atrophy, 220, 291 Muscular Dystrophies, 89, 265, 291 Mustard Gas, 283, 291 Mutagenesis, 17, 28, 50, 291 Mutagens, 291 Myalgia, 194, 291 Myelin, 6, 10, 291, 293 Myocardium, 288, 291 Myopathy, 66, 104, 291 Myopia, 291, 309 Myosin, 250, 291 Myotonic Dystrophy, 220, 291
338 Chondroitin
N Narcosis, 292 Narcotic, 202, 217, 290, 292 Natural killer cells, 62, 89, 292 Nausea, 242, 243, 265, 292 NCI, 1, 140, 213, 256, 292 Necrosis, 243, 249, 260, 280, 288, 292, 313 Neocortex, 125, 292 Neonatal, 16, 45, 292 Neoplasia, 219, 292 Neoplasm, 43, 292, 322 Neoplastic, 10, 94, 286, 292 Neoplastic meningitis, 94, 292 Nephritis, 195, 292 Nephrolithiasis, 102, 292 Nephropathy, 283, 292 Nerve Degeneration, 22, 292 Nerve Endings, 247, 292 Nerve Fibers, 189, 247, 293 Nerve Growth Factor, 293, 294 Nervous System, 6, 9, 13, 20, 22, 45, 51, 55, 152, 194, 220, 237, 238, 245, 246, 250, 254, 271, 273, 275, 284, 287, 290, 291, 292, 293, 294, 296, 299, 313, 318 Neural, 9, 17, 22, 36, 45, 55, 63, 77, 97, 238, 240, 277, 292, 293, 305 Neural Crest, 9, 293 Neural Pathways, 45, 292, 293 Neuralgia, 160, 194, 293 Neurites, 57, 185, 293 Neuritis, 161, 293 Neuroblastoma, 98, 293 Neurogenic, 55, 293 Neuroglia, 286, 293 Neuroma, 189, 293 Neuronal, 6, 9, 22, 23, 26, 33, 57, 59, 185, 189, 246, 274, 292, 293 Neuronal Plasticity, 33, 293 Neuropathy, 194, 293, 299 Neurophysiology, 262, 292, 293 Neurotransmitters, 240, 294 Neurotrophins, 20, 294 Neutralization, 29, 294 Neutrons, 239, 249, 282, 294, 308 Neutrophil, 35, 50, 92, 294 Nevirapine, 32, 294 Nickel, 7, 155, 294 Nifedipine, 202, 294 Nitric Oxide, 27, 54, 294 Nitrogen, 164, 238, 239, 240, 241, 269, 289, 294, 322 Non-nucleoside, 294
Norepinephrine, 238, 240, 264, 294 Nuclear, 48, 246, 258, 266, 269, 271, 292, 294, 295 Nuclear Localization Signal, 48, 294 Nuclear Pore, 294, 295 Nuclei, 239, 258, 266, 272, 286, 289, 294, 295, 296, 306 Nucleic acid, 51, 184, 272, 277, 279, 291, 294, 295, 304, 307 Nucleic Acid Hybridization, 277, 295 Nucleolus, 295, 311 Nucleus, 7, 10, 11, 243, 245, 246, 255, 261, 263, 269, 287, 294, 295, 305, 306, 316, 319 Nursing Care, 8, 295 Nutritive Value, 271, 295 O Occipital Lobe, 295, 324 Ocular, 245, 295 Ointments, 178, 265, 295, 314 Olfactory Bulb, 21, 55, 295, 325 Oligonucleotide Probes, 33, 295 Oligopeptides, 46, 295 Oligosaccharides, 16, 17, 57, 65, 68, 107, 109, 124, 130, 131, 295 Omega-3 fatty acid, 160, 295 Oncogene, 31, 220, 276, 295 Oncogenic, 281, 296 On-line, 24, 235, 296 Opacity, 253, 262, 296 Ophthalmic, 151, 158, 164, 183, 192, 296 Opioid Peptides, 296 Opsin, 296, 310 Optic Nerve, 240, 296, 297, 310, 311 Orderly, 42, 296 Organ Culture, 296, 320 Organ Preservation, 194, 296 Organelles, 36, 261, 287, 296, 302 Ornithine, 191, 296 Osmosis, 296 Osmotic, 12, 47, 108, 185, 239, 296 Ossification, 59, 296, 297 Osteoclasts, 15, 296 Osteogenesis, 255, 297 Osteomalacia, 149, 297 Osteopetrosis, 91, 297 Osteoporosis, 16, 149, 268, 297, 308 Osteotomy, 216, 297 Otitis, 176, 297 Overexpress, 42, 297 Ovulation, 54, 297 Oxidation, 73, 77, 92, 180, 181, 237, 243, 244, 248, 261, 273, 285, 297
Index 339
Oxidative metabolism, 284, 297 Oxygenation, 155, 297 Oxygenator, 252, 297 P Pachymeningitis, 287, 297 Palliative, 4, 297, 319 Pancreas, 237, 248, 264, 281, 283, 297, 322 Pancreatic, 5, 100, 105, 163, 219, 297 Pancreatic cancer, 219, 297 Papilla, 297 Papillary, 165, 278, 297 Parasite, 17, 32, 39, 62, 90, 100, 103, 297 Parenteral, 187, 297, 298 Parenteral Nutrition, 187, 298 Paresis, 293, 298 Paresthesias, 293, 298 Parietal, 298, 299, 302 Parity, 100, 298 Paroxysmal, 220, 298 Particle, 152, 187, 298, 321 Patch, 177, 193, 298 Pathogen, 280, 298 Pathogenesis, 3, 9, 28, 31, 32, 35, 39, 51, 166, 298 Pathologic, 29, 243, 248, 260, 278, 298, 307, 310, 324 Pathologic Processes, 243, 298 Pathologies, 14, 151, 298 Patient Compliance, 41, 298 Patient Education, 224, 230, 232, 235, 298 Pelvic, 298, 305 Pentosan polysulfate, 202, 298 Pepsin, 256, 298 Pepsin A, 256, 298 Peptide Fragments, 15, 26, 298 Peptide T, 185, 298 Perception, 165, 258, 299 Percutaneous, 155, 299 Perennial, 265, 299 Pericarditis, 161, 299 Pericardium, 299 Perineal, 299, 308 Periodontitis, 78, 299 Peripheral Nervous System, 194, 299, 311, 317 Peripheral Neuropathy, 194, 299 Peritoneal, 164, 299 Peritoneal Cavity, 164, 299 Peritoneal Dialysis, 164, 299 Peritoneum, 164, 288, 299 Peritonitis, 164, 299 Pesticides, 248, 299
Pharmaceutic Aids, 271, 299 Pharmaceutical Preparations, 194, 254, 268, 272, 299 Pharmaceutical Solutions, 265, 300 Pharmacokinetic, 300 Pharmacologic, 4, 41, 241, 275, 300, 320, 321 Pharmacotherapy, 171, 300 Phenazopyridine, 202, 300 Phenotype, 10, 19, 24, 27, 41, 42, 43, 47, 95, 109, 115, 119, 168, 300 Phenyl, 202, 300 Phenylalanine, 298, 300, 322 Phospholipases, 300, 314 Phospholipids, 270, 280, 285, 300 Phosphorus, 251, 300 Phosphorylated, 257, 300 Phosphorylation, 17, 35, 300 Photocoagulation, 257, 300 Photoreceptor, 84, 300 Physical Examination, 217, 300 Physiologic, 11, 192, 239, 248, 275, 282, 300, 305, 309, 310 Physiology, 7, 246, 266, 275, 293, 300 Pigment, 247, 287, 301 Pilocarpine, 164, 301 Pilot study, 66, 82, 87, 301 Pituitary Gland, 270, 301, 305 Placenta, 17, 33, 39, 62, 67, 73, 75, 79, 83, 100, 105, 108, 301, 304, 323 Plana, 301, 313 Plaque, 184, 185, 241, 245, 301 Plasma cells, 242, 301 Plasma protein, 187, 239, 301, 306 Plasmids, 40, 301 Plasmin, 59, 301, 320, 323 Plasminogen, 41, 59, 91, 301, 320, 323 Plasminogen Activators, 301 Plasticity, 33, 55, 60, 302 Plastids, 254, 296, 302 Platelet Activation, 29, 302, 314 Platelet Aggregation, 103, 130, 241, 294, 302, 320 Platelet Factor 4, 64, 281, 302 Platelets, 35, 74, 113, 117, 125, 244, 247, 294, 302, 309, 319, 320 Platinum, 256, 285, 302 Pleura, 302 Pleural, 103, 288, 302 Pleural cavity, 302 Pleural Effusion, 103, 302 Pleurisy, 161, 302
340 Chondroitin
Poisoning, 288, 292, 302 Pollen, 254, 303, 307 Polycystic, 220, 303 Polyethylene, 47, 101, 303 Polyhydroxyethyl Methacrylate, 113, 117, 303 Polymerase, 175, 303 Polymers, 30, 47, 144, 146, 151, 153, 167, 181, 186, 303, 306 Polymorphic, 156, 262, 303 Polypeptide, 24, 51, 157, 167, 168, 240, 257, 267, 270, 277, 298, 301, 303, 304, 306, 325 Posterior, 158, 183, 245, 255, 265, 282, 295, 297, 303, 311 Postmenopausal, 8, 23, 268, 297, 303, 308 Postnatal, 14, 89, 303, 316 Postsynaptic, 303, 314, 318 Post-translational, 18, 36, 303 Potentiates, 281, 303 Potentiating, 240, 303 Potentiation, 303, 314 Practice Guidelines, 217, 303 Precipitation, 37, 160, 304 Prenatal, 266, 272, 304 Presumptive, 21, 304 Prevalence, 16, 304 Prickle, 283, 304 Prion, 184, 185, 304 Probe, 14, 31, 37, 46, 51, 175, 295, 304 Procaine, 284, 304 Procollagen, 9, 304 Prodrug, 190, 304 Progeny, 59, 258, 304 Progesterone, 304, 316 Progression, 10, 11, 37, 51, 58, 59, 60, 78, 82, 83, 108, 149, 207, 216, 241, 304 Progressive, 73, 78, 155, 244, 253, 255, 260, 268, 274, 291, 292, 296, 302, 304, 307, 322 Projection, 262, 294, 295, 296, 304, 309 Proline, 170, 182, 257, 278, 304 Promoter, 40, 47, 57, 198, 304 Pronase, 197, 304 Prone, 176, 304 Pro-Opiomelanocortin, 271, 296, 305 Prophase, 305, 318 Prosencephalon, 263, 305, 318 Prostaglandin, 93, 305, 320 Prostaglandins A, 156, 305 Prostaglandins D, 305 Prostate, 70, 83, 219, 248, 305, 308, 310, 322 Prostatectomy, 305, 308 Prosthesis, 53, 170, 305
Protease, 15, 39, 57, 59, 160, 257, 305, 320 Protease Inhibitors, 57, 305 Protective Agents, 251, 306 Protein Binding, 18, 115, 118, 306, 320 Protein C, 16, 25, 42, 60, 148, 186, 239, 240, 243, 246, 283, 285, 306, 323 Protein Conformation, 240, 283, 306 Protein Folding, 7, 306 Protein Kinases, 35, 306 Protein S, 220, 221, 248, 272, 306, 311 Proteolytic, 130, 163, 239, 257, 267, 270, 301, 304, 306, 320, 323 Prothrombin, 306, 319 Protocol, 24, 29, 306 Protons, 239, 277, 306, 308 Protozoa, 258, 289, 301, 302, 306 Proximal, 42, 155, 264, 306 Pruritic, 265, 306 Pruritus, 264, 278, 306, 307 Psoriasis, 174, 193, 291, 307, 310 Psychology, 264, 307 Psychomotor, 252, 307 Public Health, 32, 218, 307 Public Policy, 215, 307 Publishing, 61, 157, 307 Pulmonary, 14, 166, 174, 249, 259, 260, 275, 284, 307, 317, 324 Pulmonary Fibrosis, 174, 307 Pulmonary hypertension, 260, 307 Pulse, 34, 290, 307 Pupil, 260, 289, 307 Purifying, 17, 144, 184, 263, 307 Purines, 307, 313 Purpura, 9, 307 Purulent, 81, 307 Pyridoxal, 165, 307 Q Quality of Life, 8, 38, 44, 307 Quaternary, 144, 306, 307 Quercetin, 165, 168, 199, 307 R Race, 145, 289, 307 Radiation, 41, 246, 267, 269, 270, 271, 282, 298, 308, 314, 325 Radiation therapy, 269, 271, 282, 283, 298, 308, 325 Radical prostatectomy, 83, 308 Radioactive, 7, 246, 275, 277, 279, 282, 283, 290, 294, 296, 308, 322, 325 Radiochemical, 82, 308 Radioimmunotherapy, 279, 308 Radioisotope, 295, 308
Index 341
Radiolabeled, 52, 94, 283, 308, 325 Radiological, 299, 308 Radiopharmaceutical, 30, 272, 308 Radiotherapy, 249, 283, 308, 325 Raloxifene, 23, 308, 312 Randomized, 44, 66, 87, 107, 124, 132, 210, 266, 308 Randomized clinical trial, 107, 132, 308 RANTES, 74, 85, 113, 117, 125, 308 Reactive Oxygen Species, 41, 309 Reagent, 263, 309 Receptors, Serotonin, 309, 313 Recombinant, 18, 33, 37, 40, 58, 76, 90, 102, 181, 309, 324 Recombination, 26, 258, 309 Reconstitution, 151, 309 Recovery of Function, 22, 189, 309 Rectum, 249, 264, 270, 272, 284, 305, 309, 317 Red blood cells, 17, 68, 268, 309, 311, 314 Red Nucleus, 245, 309 Refer, 1, 20, 250, 257, 271, 285, 293, 294, 308, 309 Refraction, 40, 291, 309 Refractive Errors, 240, 309 Regeneration, 6, 11, 13, 20, 22, 27, 49, 55, 81, 138, 162, 164, 173, 189, 196, 239, 270, 309 Regimen, 153, 265, 298, 300, 309 Regurgitation, 275, 309 Relaxant, 309 Renin, 41, 241, 309, 310 Renin-Angiotensin System, 41, 310 Repopulation, 55, 310 Research Support, 8, 208, 310 Resorption, 149, 296, 310 Respiration, 252, 261, 289, 290, 297, 310 Response rate, 24, 310 Restoration, 27, 34, 52, 155, 163, 189, 217, 309, 310, 325 Reticular, 165, 310 Retina, 17, 158, 183, 245, 255, 256, 284, 291, 293, 296, 310, 311, 313, 325 Retinal, 16, 258, 296, 310, 324 Retinoblastoma, 220, 310 Retinoids, 310, 325 Retinol, 310 Retropubic, 305, 308, 310 Retropubic prostatectomy, 308, 310 Reverberant, 263, 311 Rheumatic Diseases, 67, 73, 77, 86, 99, 106, 112, 116, 127, 129, 207, 208, 311
Rheumatism, 85, 86, 107, 147, 155, 163, 195, 311 Rheumatoid, 9, 58, 72, 154, 161, 163, 173, 208, 224, 257, 311 Rheumatoid arthritis, 58, 72, 154, 161, 163, 173, 208, 257, 311 Rheumatology, 4, 44, 52, 66, 72, 74, 78, 102, 108, 123, 124, 151, 202, 311 Ribose, 237, 311 Ribosome, 25, 311, 321 Rigidity, 301, 311 Rod, 7, 246, 256, 300, 311 Rutin, 307, 311 S Salicylate, 202, 311 Saliva, 88, 311 Salivary, 264, 297, 311, 317 Salivary glands, 264, 311 Saponins, 311, 316 Sarcolemma, 89, 311 Scatter, 83, 311 Schwannoma, 65, 311 Sclera, 255, 258, 268, 311 Scleritis, 161, 311 Scleroderma, 174, 244, 312 Sclerosis, 220, 244, 257, 291, 312 Screening, 40, 171, 172, 256, 272, 312 Scrotum, 312, 319 Sea Urchins, 152, 312 Sebaceous, 283, 312 Sebaceous gland, 283, 312 Secondary tumor, 288, 312 Secretory, 166, 312, 318 Sedative, 240, 264, 278, 312 Segregation, 309, 312 Seizures, 252, 298, 312 Selective estrogen receptor modulator, 308, 312 Selenium, 178, 312 Self Care, 202, 312 Semen, 305, 312 Senile, 297, 312 Sepsis, 16, 313 Septic, 244, 313 Sequence Homology, 299, 313 Sequencing, 40, 51, 313 Sequester, 39, 313 Serine, 57, 59, 157, 267, 313, 317, 320, 322 Serotonin, 202, 240, 243, 300, 309, 313, 322 Serrata, 163, 256, 313 Serrated, 313
342 Chondroitin
Serum, 19, 40, 67, 72, 80, 104, 112, 116, 149, 157, 239, 241, 257, 258, 285, 299, 302, 309, 313 Sex Characteristics, 241, 313 Sex Determination, 220, 313 Sharks, 159, 161, 190, 313 Shedding, 35, 313 Shock, 187, 254, 313, 322 Side effect, 171, 187, 192, 202, 209, 225, 238, 243, 248, 254, 265, 278, 313, 321 Signal Transduction, 11, 42, 43, 186, 251, 275, 280, 313 Silicon, 190, 314 Silicon Dioxide, 190, 314 Skeletal, 19, 42, 68, 89, 104, 113, 117, 153, 170, 241, 256, 261, 283, 291, 314, 318 Skeleton, 59, 237, 270, 283, 305, 314 Skin Aging, 165, 314 Skin Care, 198, 314 Skin graft, 314, 316 Skull, 314, 319 Sludge, 166, 314 Small intestine, 247, 256, 261, 265, 277, 282, 314, 322 Smooth muscle, 51, 71, 85, 95, 101, 107, 168, 239, 241, 250, 251, 259, 276, 290, 310, 314, 317 Sneezing, 313, 314 Soaps, 314 Social Environment, 307, 314 Sodium, 82, 105, 147, 150, 151, 163, 164, 171, 177, 191, 202, 263, 274, 314, 315 Sodium Bicarbonate, 171, 315 Soft tissue, 44, 249, 314, 315 Solid tumor, 241, 265, 315 Solvent, 147, 268, 296, 300, 315 Soma, 189, 315 Somatic, 266, 277, 287, 289, 299, 315, 319 Sorbitol, 187, 193, 315 Soybean Oil, 315, 325 Specialist, 226, 315 Specificity, 12, 15, 16, 18, 20, 28, 33, 39, 58, 130, 238, 244, 250, 267, 284, 315, 317, 320 Sperm, 241, 255, 303, 315, 319, 322 Sphincter, 284, 315 Spinal Cord Injuries, 27, 315 Spinal Nerves, 299, 315 Spinous, 268, 283, 315 Spleen, 286, 315 Splenomegaly, 297, 315 Sporadic, 310, 315 Sputum, 81, 315
Squamous, 43, 90, 268, 316 Squamous cell carcinoma, 43, 90, 268, 316 Squamous cells, 316 Stabilization, 7, 53, 54, 194, 316 Stasis, 196, 316 Steel, 155, 209, 256, 316 Stem Cells, 30, 55, 71, 112, 116, 316 Stents, 30, 316 Sterile, 150, 164, 244, 316 Steroid, 66, 104, 171, 247, 273, 275, 311, 316 Stimulant, 250, 276, 316 Stimulus, 240, 265, 280, 281, 282, 298, 316, 319 Stomach, 237, 264, 268, 272, 277, 282, 292, 298, 299, 314, 315, 316 Strand, 303, 316 Stress, 52, 53, 145, 195, 245, 251, 253, 254, 292, 311, 316, 323 Stroke, 141, 214, 252, 316 Stroma, 40, 46, 59, 282, 316 Stromal, 40, 46, 83, 105, 316 Stupor, 292, 316 Subacute, 280, 317 Subclinical, 280, 312, 317 Subcutaneous, 37, 114, 117, 165, 297, 317 Subiculum, 276, 317 Submaxillary, 267, 317 Subspecies, 315, 317 Substance P, 288, 309, 312, 317 Substrate, 9, 15, 37, 45, 49, 59, 79, 144, 153, 157, 158, 167, 196, 267, 317 Substrate Specificity, 15, 157, 158, 167, 317 Subtilisin, 48, 317 Sulfates, 30, 56, 69, 78, 80, 86, 92, 93, 95, 100, 102, 107, 109, 129, 131, 132, 146, 148, 150, 153, 157, 160, 164, 170, 173, 174, 195, 317 Sulfotransferases, 40, 56, 96, 97, 158, 317 Sulfur, 74, 179, 263, 269, 288, 317 Sulfuric acid, 180, 240, 317 Supplementation, 62, 107, 128, 132, 317 Suppositories, 147, 272, 317 Suppression, 18, 132, 317 Suppressive, 22, 317 Surfactant, 14, 317 Sympathomimetic, 264, 268, 294, 317 Symphysis, 305, 318 Symptomatic, 24, 62, 82, 105, 128, 131, 154, 172, 195, 318 Synapses, 294, 295, 318 Synapsis, 318 Synaptic, 33, 239, 314, 318
Index 343
Synergistic, 168, 169, 199, 318 Synovial Fluid, 19, 75, 77, 93, 104, 107, 108, 115, 118, 162, 176, 197, 208, 318 Synovial Membrane, 151, 283, 318 Synovitis, 176, 177, 318 Systemic, 41, 42, 161, 217, 243, 249, 250, 257, 268, 278, 280, 283, 308, 312, 315, 318, 322, 325 Systemic disease, 161, 278, 318 Systolic, 278, 318 T Talus, 60, 318 Tarsal Bones, 318 Tarsus, 318 Tear Gases, 283, 318 Telangiectasia, 220, 318 Telencephalon, 21, 246, 305, 318 Telomerase, 29, 319 Temporal, 9, 11, 18, 22, 33, 37, 42, 102, 276, 287, 319 Tendonitis, 163, 319 Terminalis, 318, 319 Testicles, 146, 312, 319 Testicular, 130, 132, 319 Testis, 319 Thalamic, 245, 319 Thalamic Diseases, 245, 319 Therapeutics, 51, 56, 104, 184, 187, 319 Thermal, 44, 249, 264, 275, 294, 319 Thermoregulation, 165, 319 Thigh, 270, 319 Thimerosal, 158, 183, 319 Thoracic, 20, 263, 302, 319 Thorax, 237, 285, 319 Threonine, 49, 299, 313, 319 Threshold, 263, 278, 319 Thrombin, 28, 29, 57, 91, 270, 302, 306, 319 Thrombocytes, 302, 319 Thrombocytopenia, 29, 319 Thrombolytic, 301, 319 Thrombomodulin, 50, 75, 102, 306, 319 Thrombosis, 28, 30, 91, 95, 174, 247, 281, 306, 316, 320 Thromboxanes, 244, 320 Thrombus, 260, 280, 302, 319, 320 Thymidine, 188, 320 Thymus, 286, 320 Thyroid, 320, 323 Tin, 299, 302, 320 Tinnitus, 297, 320 Tissue Culture, 9, 112, 116, 293, 320 Tissue Distribution, 250, 320
Tissue Plasminogen Activator, 59, 320 Tonsils, 75, 113, 320 Tooth Preparation, 237, 320 Topical, 66, 124, 163, 170, 177, 178, 182, 191, 192, 193, 205, 217, 268, 314, 315, 319, 320 Torsion, 11, 280, 320 Toxic, iv, 58, 240, 245, 258, 261, 262, 265, 267, 274, 279, 293, 312, 320, 321 Toxicity, 185, 187, 265, 300, 321 Toxicokinetics, 321 Toxicology, 51, 216, 321 Toxins, 240, 242, 267, 273, 280, 290, 308, 321 Trace element, 187, 249, 294, 314, 320, 321 Trachea, 146, 161, 169, 199, 250, 284, 320, 321 Traction, 256, 321 Tragacanth, 180, 321 Transcriptase, 29, 294, 319, 321 Transcription Factors, 23, 42, 321 Transduction, 11, 34, 43, 313, 321 Transfection, 7, 15, 29, 40, 41, 248, 321 Transferases, 128, 274, 321 Transforming Growth Factor beta, 27, 321 Transgenes, 31, 321 Translation, 36, 321 Translational, 19, 45, 321 Translocation, 17, 108, 322 Transmitter, 237, 245, 264, 282, 287, 293, 294, 318, 322 Transplantation, 5, 27, 29, 55, 84, 166, 194, 216, 255, 322 Trauma, 33, 151, 173, 175, 203, 246, 275, 292, 309, 319, 320, 322 Tricuspid Atresia, 260, 322 Trisomy, 241, 322 Trophic, 292, 322 Trypsin, 40, 108, 267, 322 Tryptophan, 257, 313, 322 Tuberculosis, 259, 285, 322 Tuberous Sclerosis, 220, 322 Tubulin, 37, 289, 322 Tumor marker, 248, 322 Tumorigenic, 10, 322 Tumour, 271, 322 Tympanic membrane, 176, 322 Type 2 diabetes, 107, 132, 322 Tyrosine, 17, 63, 146, 264, 322 U Ulcer, 262, 323 Ulceration, 262, 323
344 Chondroitin
Ultrafiltration, 164, 275, 323 Umbilical Arteries, 323 Umbilical Cord, 146, 150, 176, 323 Unconscious, 241, 262, 278, 323 Urea, 164, 296, 323 Ureters, 323 Urethra, 305, 323 Uric, 274, 278, 307, 323 Urinary, 108, 109, 171, 202, 251, 261, 300, 305, 310, 320, 323 Urinary Plasminogen Activator, 320, 323 Urinary tract, 171, 172, 300, 323 Urinate, 323, 325 Urine, 19, 91, 99, 149, 150, 248, 260, 264, 267, 273, 276, 323 Urticaria, 254, 278, 323 Uterus, 254, 262, 304, 323 V Vaccine, 17, 33, 238, 306, 323 Vacuoles, 267, 296, 323 Vagina, 254, 263, 323 Valves, 150, 323 Vasculitis, 161, 324 Vasoconstriction, 268, 324 Vasodilator, 249, 265, 276, 294, 324 Vasomotor, 268, 324 Vector, 48, 280, 321, 324 Vein, 282, 294, 323, 324 Venous, 196, 247, 250, 306, 322, 324 Ventricle, 243, 245, 259, 276, 307, 318, 322, 324 Ventricular, 21, 23, 259, 322, 324 Venules, 56, 249, 251, 324 Vertebrae, 282, 315, 324 Vertebral, 189, 301, 324 Vertigo, 297, 324 Veterinary Medicine, 215, 324 Vinblastine, 322, 324 Vincristine, 322, 324
Viral, 32, 260, 296, 321, 322, 324, 325 Viral Load, 32, 324 Virulence, 321, 324 Virus, 64, 114, 117, 195, 246, 267, 272, 274, 281, 301, 321, 324 Visceral, 245, 299, 324 Viscosity, 54, 129, 277, 324 Visual Acuity, 312, 324 Visual Cortex, 25, 240, 324 Vitamin A, 148, 280, 310, 325 Vitamin E, 148, 325 Vitreous Body, 158, 183, 310, 325 Vitreous Humor, 158, 183, 184, 325 Vitro, 5, 8, 10, 14, 18, 20, 21, 22, 23, 25, 26, 27, 28, 30, 31, 35, 37, 38, 40, 41, 42, 43, 49, 51, 52, 53, 55, 61, 65, 71, 91, 125, 166, 184, 185, 188, 276, 280, 320, 325 Vivo, 5, 8, 10, 11, 13, 14, 18, 20, 22, 23, 25, 26, 30, 42, 43, 47, 49, 53, 54, 55, 58, 61, 62, 83, 91, 99, 128, 152, 162, 185, 276, 280, 320, 325 Void, 144, 325 Vomeronasal Organ, 295, 325 W Warts, 191, 325 Weight-Bearing, 154, 325 White blood cell, 242, 284, 286, 290, 292, 294, 301, 325 Wound Healing, 12, 134, 145, 146, 162, 167, 184, 192, 253, 270, 281, 287, 325 Wounds, Gunshot, 315, 325 X Xenograft, 5, 241, 325 X-ray, 16, 270, 271, 282, 286, 294, 308, 325 X-ray therapy, 283, 325 Y Yeasts, 271, 300, 325 Z Zymogen, 306, 325
Index 345
346 Chondroitin
Index 347
348 Chondroitin
