Myasthenia Gravis - A Medical Dictionary, Bibliography, and Annotated Research Guide to Internet References

MYASTHENIA GRAVIS A M EDICAL D ICTIONARY , B IBLIOGRAPHY , AND A NNOTATED R ESEARCH G UIDE TO I NTERNET R E FERENCES J ...

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MYASTHENIA GRAVIS A M EDICAL D ICTIONARY , B IBLIOGRAPHY , AND A NNOTATED R ESEARCH G UIDE TO I NTERNET R E FERENCES

J AMES N. P ARKER , M.D. AND P HILIP M. P ARKER , P H .D., E DITORS

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ICON Health Publications ICON Group International, Inc. 4370 La Jolla Village Drive, 4th Floor San Diego, CA 92122 USA Copyright 2004 by ICON Group International, Inc. Copyright 2004 by ICON Group International, Inc. All rights reserved. This book is protected by copyright. No part of it may be reproduced, stored in a retrieval system, or transmitted in any form or by any means, electronic, mechanical, photocopying, recording, or otherwise, without written permission from the publisher. Printed in the United States of America. Last digit indicates print number: 10 9 8 7 6 4 5 3 2 1

Publisher, Health Care: Philip Parker, Ph.D. Editor(s): James Parker, M.D., Philip Parker, Ph.D. Publisher's note: The ideas, procedures, and suggestions contained in this book are not intended for the diagnosis or treatment of a health problem. As new medical or scientific information becomes available from academic and clinical research, recommended treatments and drug therapies may undergo changes. The authors, editors, and publisher have attempted to make the information in this book up to date and accurate in accord with accepted standards at the time of publication. The authors, editors, and publisher are not responsible for errors or omissions or for consequences from application of the book, and make no warranty, expressed or implied, in regard to the contents of this book. Any practice described in this book should be applied by the reader in accordance with professional standards of care used in regard to the unique circumstances that may apply in each situation. The reader is advised to always check product information (package inserts) for changes and new information regarding dosage and contraindications before prescribing any drug or pharmacological product. Caution is especially urged when using new or infrequently ordered drugs, herbal remedies, vitamins and supplements, alternative therapies, complementary therapies and medicines, and integrative medical treatments. Cataloging-in-Publication Data Parker, James N., 1961Parker, Philip M., 1960Myasthenia Gravis: 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: 0-597-84123-3 1. Myasthenia Gravis-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.

Copyright Notice If a physician wishes to copy limited passages from this book for patient use, this right is automatically granted without written permission from ICON Group International, Inc. (ICON Group). However, all of ICON Group publications have copyrights. With exception to the above, copying our publications in whole or in part, for whatever reason, is a violation of copyright laws and can lead to penalties and fines. Should you want to copy tables, graphs, or other materials, please contact us to request permission (E-mail: [email protected]). ICON Group often grants permission for very limited reproduction of our publications for internal use, press releases, and academic research. Such reproduction requires confirmed permission from ICON Group International Inc. The disclaimer above must accompany all reproductions, in whole or in part, of this book.

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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 myasthenia gravis. 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 MYASTHENIA GRAVIS .............................................................................. 3 Overview........................................................................................................................................ 3 The Combined Health Information Database................................................................................. 3 Federally Funded Research on Myasthenia Gravis........................................................................ 4 E-Journals: PubMed Central ....................................................................................................... 32 The National Library of Medicine: PubMed ................................................................................ 34 CHAPTER 2. NUTRITION AND MYASTHENIA GRAVIS..................................................................... 79 Overview...................................................................................................................................... 79 Finding Nutrition Studies on Myasthenia Gravis ...................................................................... 79 Federal Resources on Nutrition ................................................................................................... 85 Additional Web Resources ........................................................................................................... 86 CHAPTER 3. ALTERNATIVE MEDICINE AND MYASTHENIA GRAVIS .............................................. 87 Overview...................................................................................................................................... 87 National Center for Complementary and Alternative Medicine.................................................. 87 Additional Web Resources ........................................................................................................... 93 General References ....................................................................................................................... 94 CHAPTER 4. DISSERTATIONS ON MYASTHENIA GRAVIS ................................................................ 95 Overview...................................................................................................................................... 95 Dissertations on Myasthenia Gravis ........................................................................................... 95 Keeping Current .......................................................................................................................... 96 CHAPTER 5. CLINICAL TRIALS AND MYASTHENIA GRAVIS ........................................................... 97 Overview...................................................................................................................................... 97 Recent Trials on Myasthenia Gravis ........................................................................................... 97 Keeping Current on Clinical Trials ............................................................................................. 97 CHAPTER 6. PATENTS ON MYASTHENIA GRAVIS ........................................................................... 99 Overview...................................................................................................................................... 99 Patents on Myasthenia Gravis..................................................................................................... 99 Patent Applications on Myasthenia Gravis............................................................................... 112 Keeping Current ........................................................................................................................ 118 CHAPTER 7. BOOKS ON MYASTHENIA GRAVIS............................................................................. 121 Overview.................................................................................................................................... 121 Book Summaries: Federal Agencies............................................................................................ 121 Book Summaries: Online Booksellers......................................................................................... 122 The National Library of Medicine Book Index ........................................................................... 124 Chapters on Myasthenia Gravis ................................................................................................ 125 CHAPTER 8. MULTIMEDIA ON MYASTHENIA GRAVIS .................................................................. 131 Overview.................................................................................................................................... 131 Bibliography: Multimedia on Myasthenia Gravis ..................................................................... 131 CHAPTER 9. PERIODICALS AND NEWS ON MYASTHENIA GRAVIS ............................................... 133 Overview.................................................................................................................................... 133 News Services and Press Releases.............................................................................................. 133 Newsletter Articles .................................................................................................................... 135 Academic Periodicals covering Myasthenia Gravis ................................................................... 136 CHAPTER 10. RESEARCHING MEDICATIONS................................................................................. 137 Overview.................................................................................................................................... 137 U.S. Pharmacopeia..................................................................................................................... 137 Commercial Databases ............................................................................................................... 139 Researching Orphan Drugs ....................................................................................................... 140 APPENDIX A. PHYSICIAN RESOURCES .......................................................................................... 143 Overview.................................................................................................................................... 143

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NIH Guidelines.......................................................................................................................... 143 NIH Databases........................................................................................................................... 145 Other Commercial Databases..................................................................................................... 147 The Genome Project and Myasthenia Gravis............................................................................. 147 APPENDIX B. PATIENT RESOURCES ............................................................................................... 153 Overview.................................................................................................................................... 153 Patient Guideline Sources.......................................................................................................... 153 Associations and Myasthenia Gravis......................................................................................... 158 Finding Associations.................................................................................................................. 159 APPENDIX C. FINDING MEDICAL LIBRARIES ................................................................................ 161 Overview.................................................................................................................................... 161 Preparation................................................................................................................................. 161 Finding a Local Medical Library................................................................................................ 161 Medical Libraries in the U.S. and Canada ................................................................................. 161 ONLINE GLOSSARIES................................................................................................................ 167 Online Dictionary Directories ................................................................................................... 170 MYASTHENIA GRAVIS DICTIONARY.................................................................................. 173 INDEX .............................................................................................................................................. 249

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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 myasthenia gravis 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 myasthenia gravis, 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 myasthenia gravis, 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 myasthenia gravis. 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 myasthenia gravis, 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 myasthenia gravis. 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 MYASTHENIA GRAVIS Overview In this chapter, we will show you how to locate peer-reviewed references and studies on myasthenia gravis.

The Combined Health Information Database The Combined Health Information Database summarizes studies across numerous federal agencies. To limit your investigation to research studies and myasthenia gravis, 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 “myasthenia gravis” (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: •

Myasthenia Gravis: Dental Treatment Considerations Source: SCD. Special Care in Dentistry. 17(1): 25-32. January-February 1997. Summary: Myasthenia gravis (MG) is an autoimmune neuromuscular disorder that presents challenges for the dental practitioner. Facial and masticatory muscles may be involved and complicate dental treatment. Exacerbation of the skeletal muscle weakness and fatigability that characterize this disorder can be precipitated by certain medications used in dentistry. In this article, the authors review the epidemiology, clinical features, diagnosis, and treatment of MG; describe the dental treatment experience of patients with MG seen in a hospital-based dental clinic; and discuss special considerations, including drug precautions, for the effective management of patients with MG in dental practice. A review of 47 dental treatment episodes in 16 patients with MG was

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undertaken to identify neuromuscular responses to dental treatment and post-dental treatment medical therapy required for control of resultant exacerbations of muscular weakness. Neuromuscular sequalae occurred in 5 treatment episodes for four different patients. 4 figures. 3 tables. 25 references. (AA-M). •

Orthognathic Surgery in Patients with Congenital Myasthenia Gravis Source: Journal of Oral and Maxillofacial Surgery. 54(6): 705-714. June 1996. Summary: This article describes orthognathic surgery in patients with congenital myasthenia gravis (CMG), a neuromuscular transmission disorder of the skeletal muscles. Topics covered include the classification system for CMG, symptoms, and therapy for CMG. The bulk of the article consists of case reports of three patients with CMG who have undergone orthognathic surgery. The authors describe the clinical and cephalometric findings, surgical workup, and perianesthetic considerations. Nasopharyngoscopy was also performed in these patients. 3 figures. 47 references. (AAM).

Federally Funded Research on Myasthenia Gravis The U.S. Government supports a variety of research studies relating to myasthenia gravis. These studies are tracked by the Office of Extramural Research at the National Institutes of Health.2 CRISP (Computerized Retrieval of Information on Scientific Projects) is a searchable database of federally funded biomedical research projects conducted at universities, hospitals, and other institutions. Search the CRISP Web site at http://crisp.cit.nih.gov/crisp/crisp_query.generate_screen. You will have the option to perform targeted searches by various criteria, including geography, date, and topics related to myasthenia gravis. 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 myasthenia gravis. The following is typical of the type of information found when searching the CRISP database for myasthenia gravis: •

Project Title: 3,4 DIAMINOPYRIDINE IN LAMBERT EATON MYASTHENIC SYNDROME Principal Investigator & Institution: Sanders, Donald B.; Duke University Durham, Nc 27706 Timing: Fiscal Year 2001 Summary: This project was a prospective, placebo-controlled, randomized study to evaluate the effectiveness of 3,4-diaminopyridine (DAP) in patients with Lambert-Eaton myasthenic syndrome (LEMS), and to determine the common short and long term sideeffects of DAP. (DAP is an orphan drug that has been used elsewhere in the world for over 20 years to improve strength in patients with LEMS, myasthenia gravis [MG], and congenital myasthenic syndromes. In many countries it is considered standard therapy

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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for LEMS.) Twenty six patients with LEMS completed a 2-arm parallel treatment protocol in which DAP, 20 mg tid, or placebo was given blindly for 6 days, and a quantitative examination of muscle strength was used as the primary measure of efficacy. The last patient completed the blinded, in-patient protocol in May, 1998, and 3 months later the assignment code was broken. Twelve patients had received DAP and 14 had received placebo. There was no difference in the age of LEMS onset, gender distribution, incidence of lung cancer, or baseline muscle strength between the placebo and active drug groups. Analysis by 2-tailed t-test demonstrated that patients who had received DAP had a significantly greater improvement in the quantitative measure of neuromuscular function and in a physiologic measurement of muscle electrical response. There was also a significant improvement in a physician-applied assessment of muscle strength in limb muscles. After the blinded study, patients were given openlabel DAP and monitored for side effects as long as there was symptomatic improvement. All but one LEMS patient had significant symptomatic improvement from subsequent open-label administration of DAP. Side-effects of DAP were negligible, consisting of perioral and digital paresthesias. Laboratory measurements demonstrated no evidence of toxicity affecting liver, renal, hematologic, endocrinologic, encephalographic or electrocardiologic function acutely or after 6 months of open-label DAP. This study corroborates previous studies and many years of clinical experience which suggest that DAP is an effective and safe treatment for most patients with LEMS and should be available for clinical use in this country. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •

Project Title: ADENOSINE DERIVATIVES AND SYNAPTIC TRANSMISSION Principal Investigator & Institution: Silinsky, Eugene M.; Professor; Mol Pharm & Biol Chemistry; Northwestern University Office of Sponsored Programs Chicago, Il 60611 Timing: Fiscal Year 2001; Project Start 01-MAY-1979; Project End 31-MAR-2004 Summary: (Adapted from applicant's abstract) The overall objective of the proposed research is to further our knowledge of the molecular mechanisms by which adenosine derivatives affect the vertebrate nervous system. During this past period of support, we found that ATP is released together with the neurotransmitter acetylcholine (ACh) within milliseconds of a nerve impulse and, after hydrolysis to adenosine, is the physiological mediator of skeletal neuromuscular depression. We also found evidence for mutually-inhibitory interactions between nicotinic ACh receptors and P2X ATP receptors in adult mammalian neurons. During the next period of support, we will continue to study the behavior of adenosine derivatives as presynaptic inhibitors of ACh release and postsynaptic inhibitors of the action of ACh on nicotinic synapses. There are two specific aims underlying the overall objective as follows. For specific aim 1, we will attempt to determine the specific molecular mechanisms responsible for the inhibitory effect of adenosine on ACh release. Towards this aim, we will activate or interfere with specific target proteins in the nerve ending and examine if the effects of adenosine are altered. For specific aim 2, we will study the mechanisms underlying the inhibitory electrophysiological interactions between nicotinic ACh receptors and P2X ATP receptors on adult mammalian sympathetic neurons. Such interactions have been found to occur even with very low concentrations of ATP and nicotine. With regards to the significance of the proposed research, adenosine derivatives have been implicated as mediators of physiological and pathological activity in the vertebrate nervous system. The experiments at the neuromuscular junction demonstrate that endogenous adenosine is a physiological mediator of neuromuscular depression at frog and mammalian synapses. Determining the specific nerve terminal targets for the inhibitory actions of

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adenosine would thus provide both important basic science information and potential clinical benefits. For example, it is possible that selective adenosine receptor antagonists can be used to prevent the debilitating neuromuscular depression that occurs in patients with neuromuscular disorders such a myasthenia gravis. The results with ATP will provide valuable additional knowledge on the relationship between purinergic and nicotinic synapses in mammals. Indeed, fast excitatory purinergic transmission with similar properties to the neurons we study occurs in regions of the CNS associated with cholinergic synapses and with Alzheimer's disease. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •

Project Title: ANALYSIS OF SYNAPTIC TRANSMISSION MUTANTS IN DROSOPHILA Principal Investigator & Institution: Rivlin, Patricia K.; Neurobiology and Behavior; Cornell University Ithaca Office of Sponsored Programs Ithaca, Ny 14853 Timing: Fiscal Year 2002; Project Start 16-NOV-2001 Summary: Defects in neurotransmitter release, synthesis and storage are implicated in a number of diseases that include depression, Parkinson's disease and myasthenia gravis. Knowledge of the molecular mechanisms that underlie neurotransrnitter release will undoubtedly improve our ability to treat patients with these diseases. Three proteins have been found to be directly involved in the vesicular release of neurotransmitter: SNAP-25 (synaptosomal-associated protein of 25kDa), synaptobrevin (neuronal synaptobrevin (n-syb) in Drosophila), and syntaxin (syx). In vitro studies in both verterbrates and Drosophila have demonstrated that these three proteins interact to form a core complex by coil-coiled interactions of amphipathic helices. This complex is hypothesized to mediate the fusion of neurotransmitter-containing vesicles with the presynaptic membrane. In order to study the role of SNAP-25 in neurotransmitter release, our lab has recently generated a temperature-sensitive (ts) allele for SNAP-25 that results in enhanced neurotransmitter release. Using molecular, genetic and cellular approaches, the first phase of this proposal is aimed at uncovering the mechanisms that alter transmitter release in this SNAP ts allele. The second phase of this proposal involves the study of other ts paralytic mutations generated in our laboratory. The objective of this second study is to identify the gene responsible for the paralytic mutation and characterize its role in synaptic transmission. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen

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Project Title: ANTIGEN BASED HETEROPOLYMERS Principal Investigator & Institution: Taylor, Ronald P.; Professor; Biochem & Molecular Genetics; University of Virginia Charlottesville Box 400195 Charlottesville, Va 22904 Timing: Fiscal Year 2002; Project Start 20-FEB-1996; Project End 30-JUN-2005 Summary: There is no text on file for this abstract. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen

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Project Title: AUTOIMMUNITY TO ACETYLCHOLINE RECEPTORS Principal Investigator & Institution: Conti-Fine, Bianca M.; Distinguished Mcnight University Profess; Biochem/Mole Biol/Biophysics; University of Minnesota Twin Cities 200 Oak Street Se Minneapolis, Mn 554552070 Timing: Fiscal Year 2001; Project Start 01-APR-1987; Project End 28-FEB-2003

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Summary: (Adapted from the investigator's abstract): Mouse experimental myasthenia gravis (EMG) is induced by immunization with nicotinic acetylcholine receptor (AChR). Preliminary studies suggest that anti-AChR Th1 cells are pathogenic, Th2 cells are protective. Other findings suggest that the pathogenic potential of anti-AChR CD4+ cells in EMG is related to their epitope specificity. In addition, in human myasthenia gravis (MG), Th1 cells are pathogenic and Th2 cells might be protective. If this model will be verified in EMG, it might open the door to effective immunomodulatory approaches for MG. The overall question to be addressed using mouse EMG as a model is: whether it is the CD4+ subtype, or the epitope specificity, or both that makes an anti-AChR CD4+ cell pathogenic. The specific aims will be: (1) to determine the role(s) of anti-AChR Th1 and Th2 in mouse EMG, by investigating the effects on susceptibility to EMG of manipulations of the Th1/Th2 balance obtained by altering the cytokine environment in an effort to test the hypothesis that Th1 cells are pathogenic and Th2 cells are protective; (2) to investigate the relationship between the epitope repertoire recognized by CD4+ cells on the AChR and sensitization of Th1 or Th2 cells in order to test the hypothesis that the epitope repertoire of anti-AChR CD4+ cells correlates with their propensity to EMG because it correlates with sensitization of Th1 or Th2 cells; and to also test the hypothesis that preferential Th2 sensitization against some AChR epitopes occurs either by virtue of their limited presentation and reduced TCR occupancy, or by an imperfect interaction of the peptide/MHC complex with the TCR, similar to that described for altered peptide ligands; (3) to investigate the ability of Th1 and Th2 cells specific for different AChR epitopes to facilitate or prevent EMG in order to test the hypothesis that the epitope recognized by anti-AChR CD4+ cells influences their pathogenic or protective potential and to investigate whether this is because certain epitopes are better processed and presented and able to sensitize more CD4+ cells, or because they are recognized by CD4+ cells that help synthesis of pathogenic antibody; and (4) to investigate the effects on EMG of treatments which affect the Th1/Th2 balance and to find drug treatments that might be useful in the management of MG, and exposure to antigen from pathogens known to preferentially stimulate a Th1 or Th2 response. The latter experiments will test the hypothesis that infectious diseases might affect antibodymediated autoimmunity by acting on the Th1/Th2 balance. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •

Project Title: AUTOIMMUNITY TO CALCIUM CHANNELS IN LAMBERT EATON SYNDRO Principal Investigator & Institution: Kim, Yong I.; Scientist; Biomedical Engineering; University of Virginia Charlottesville Box 400195 Charlottesville, Va 22904 Timing: Fiscal Year 2001; Project Start 05-JUL-1999; Project End 30-APR-2003 Summary: The autoimmune response in the Lambert-Eaton myasthenic syndrome (LES), is thought to be triggered by the presence of a tumor, particularly small-cell lung cancer (SCLC). Presynaptic calcium channels at the neuromuscular junction (NMJ) are the target of the antibodies in I S patients, thus it is reasonable to assume that the putative autoantigens in SCLC cells possess the same molecular characteristics as the P/O-type Ca2+ channels found at the human NMJ. The current proposal is aimed at verifying a central hypothesis: SCLc cells express omega-agatoxin WA-sensitive P/Qtype voltage-dependent Ca2+ channels (VDCCs), which act as the primary immunogen in this disease; these channels initiate and maintain LBS patient's autoimmune response and the autoantibodies so produced then destructively cross-react with the target antigens at the NMJ. The long term objective of this proposal is two-fold: 1) to identify the primary and secondary autoantigens that initiate and maintain the production of

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pathogenic antibodies in L S; and 2) to determine their pathogenic role in clinical manifestation of the peripheral motor and autonomic nervous system dysfunctions characterizing this disease. This study will pursue four Specific Aims: [1] To determine the specificity of L S autoantibodies for subtypes of VDCCs; [2] To determine the crossreactivity of LBS IgG using cloned alpha1 Ca2+ channel subunit currents expressed in stably transfected human embryonic kidney (HBK293) cell lines and Xenopus oocytes; [3] To develop and characterize an experimental autoimmune animal model of the Lambert-Baton syndrome (EALES); and [4] To determine P/Q-type Ca2+ channel vs. synaptotagmin dysfunction at the NMJs of mice with passively transferred LES. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •

Project Title: AUTOREACTIVITY TO ACHR IN THE THYMUS OF MG PATIENTS Principal Investigator & Institution: Berrih-Aknin, Sonia; Hopital Marie Lannelongue 133 Avenue De La Resistance Le Plessis-Robinson, Timing: Fiscal Year 2001; Project Start 24-SEP-2001; Project End 31-AUG-2005 Summary: provided by applicant): Autoreactivity to AChR in the thymus of MG patientsMyasthenia Gravis (MG) is a disease caused by anti-acetylcholine receptor (AChR) autoantibodies. The thymus is clearly involved in the pathogenesis of MG: 50 percent of patients show thymic hyperplasia and 15 to 20 percent a thymoma; thymectomy is an efficient treatment for many patients. Our hypothesis is that the onset of MG disease with thymic hyperplasia is due to a coincidence of several components: the presence of the autoantigen, predisposition genes (namely MHC and cytokine genes) and a triggering event. In this favorable genetic situation, the triggering event could induce over activation of the immune system. Since AChR is present in the thymus and is highly immunogenic, and could be over expressed after the activation of the immune system, it could be efficiently presented. These events would lead to the formation of germinal centers and to production of anti-AChR antibodies inside the thymus. The long-term objectives of this application are to devise new approaches for treating MG disease. We must first understand the mechanisms underlying the induction of the antiAChR autoimmune response in the thymus of MG patients. The specific aims are to identify molecular and cellular components of the thymus that may be involved in inducing the anti-AChR autoimmune response and to create new models of thymic hyperplasia based on the data obtained. Several questions will be addressed: 1) Is the pattern of AChR expression normal in the thymic tissue of MG patients? Is AChR up regulated by mediators present in the thymus of MG patients? 2) Is the immune system dysregulated? Are the number and distribution of regulatory cells normal? 3) What are the phenotypic and functional characteristics of the autoreactive T cell clones isolated from the MG thymuses? 4) Where are the autoreactive B cells located in the thymus? and what are their frequencies? 5) What is the cascade of events leading to thymic hyperplasia? How to create an experimental model with thymic hyperplasia? The first 2 objectives will help to define the accurate state of the abnormalities in thymic hyperplasia; the objectives 3 and 4 will characterize the T and B cells involved in the pathogenesis and will be very helpful for defining new therapeutics. Finally if the components relevant for thymic hyperplasia are well defined, we should be able to create a new experimental model in which the pathophysiological role of these components will be directly evidenced and where the cascade of events leading to the thymic anti-AChR antibody production could be easily manipulated. Our project is original because we aim to study physiopathological mechanisms directly at the effector site using the relevant material. Patients with MG undergo thymectomy in our hospital. A large collection of pathological human tissue is available and represents an

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outstanding research material. Several methods will be used: quantitative autoradiography, quantitative RT-PCR, microarrays, transfection, digital image analysis, microdissection, flow cytometry, T cell clones, in situ hybridization, ELISA, alphabungarotoxin binding assays, SCID mice. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •

Project Title: CEREBRAL MECHANISMS UNDERLYING DYSPNEA Principal Investigator & Institution: Banzett, Robert B.; Associate Professor; Environmental Health; Harvard University (Sch of Public Hlth) Public Health Campus Boston, Ma 02460 Timing: Fiscal Year 2002; Project Start 01-SEP-1991; Project End 28-FEB-2005 Summary: This abstract is not available. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen

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Project Title: CHARACTERIZATION OF THE HUMAN HAIR CELL RECEPTOR ALPHA-9 Principal Investigator & Institution: Lustig, Lawerence R.; Professor; Otolaryn & Head & Neck Surgery; Johns Hopkins University 3400 N Charles St Baltimore, Md 21218 Timing: Fiscal Year 2001; Project Start 01-AUG-2000; Project End 31-JUL-2005 Summary: The family of nicotinic acetylcholine receptors supports chemical synaptic transmission throughout the nervous system, including efferent, or centrifugal regulation of the inner ear. While cholinergic innervation of the inner-ear has been studied in several animal models, our understanding of cholinergic transmission within the human inner ear is quite limited. We propose here to undertake molecular, electrophysiological and histological studies of a putative nicotinic receptor, alpha-9, in the human inner ear. This work will provide not only a molecular basis for the cholinergic modulation of human hair cells, but also will establish targets of novel therapies for diseases such as vertigo and tinnitus. Furthermore, mutations and disorders of nicotinic receptor function have been implicated in such diverse diseases as myasthenia gravis, nocturnal frontal lobe epilepsy and schizophrenia. Thus, the present work may also have wider implications for understanding otologic diseases without a known etiology, including autoimmune inner ear disorders or M ni re's syndrome. Recent work in our lab has led to the identification of the human ortholgue of alpha-9, included a complete elucidation of its cDNA and genomic sequence. The goal of the current research proposal is to fully characterize this newly identified receptor, which is a likely mediator of the efferent cholinergic response in the human inner-ear. Ongoing work during the initial characterization will include the search for splice variants within human tissue, as well as further genomic analysis of its regulatory elements. The second phase of the project will include the cellular localization of the alpha-9 gene product within surgically-derived hair populations and other tissue types. The third phase of the project will include functional expression of human alpha-9 to evaluate its physiologic response to acetylcholine and its antagonists. The final phase of the project will employ these same techniques in an effort to identify additional cholinergic receptor types that may be involved in efferent cholinergic transmission within the inner- ear. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen

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Myasthenia Gravis

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Project Title: CHARACTERIZATION OF THE MUSK SIGNALING PATHWAY Principal Investigator & Institution: Fliss, Albert; Physiology; University of Maryland Balt Prof School Baltimore, Md 21201 Timing: Fiscal Year 2001; Project Start 01-JUN-2001 Summary: The goal of this proposal is to characterize the agrin/MuSK signaling pathway. Both agrin and MuSK are required for the formation of differentiated neuromuscular junctions. However, to date, it is unclear as to what is downstream of MuSK in this pathway. The specific aims of this proposal are: to identify molecules that bind to the intracellular domain of MuSK; to characterize the role of these components in acetylcholine receptor clustering (AChR); and to determine the role of tropomyosin in AChR cluster and neuromuscular junction formation. A yeast two-hybrid screen will be utilized in order to identify potential MuSK binding polypeptides. Subsequently, these binding proteins will be characterized using immunofluorescence, immunoprecipitations, deletion and co- transfection analysis to determine their role in AChR clustering. Results from these experiments will further the understanding of the development of neuromuscular junctions and neurodegenerative diseases including muscular dystrophies and myasthenia gravis. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen

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Project Title: CLASS I MOLECULES AND AUTOIMMUNITY Principal Investigator & Institution: Roopenian, Derry C.; Senior Staff Scientist; Jackson Laboratory 600 Main St Bar Harbor, Me 04609 Timing: Fiscal Year 2003; Project Start 01-MAY-1999; Project End 31-JUL-2007 Summary: (provided by applicant): IgG is the major antibody isotype responsible for a wide diversity of autoimmune diseases. A major goal would thus be to understand how one controls the levels of pathogenic IgG antibodies in individuals with autoimmune disease. Studies culminating in our recent gene targeting and transgenic experiments have suggested that the MHC class I-like IgG protection receptor, FcRn, plays a key role in maintaining endogenous IgG concentrations in mammals of all ages. Our studies indicate that FcRn is a key control point for IgG-mediated immune responses. The overall goal of the proposed studies is thus to elucidate the biology and function of FcRn in normal and autoimmune states. Our new results provide the first direct evidence that FcRn is an important molecule for humoral autoimmunity. Aim 1 will determine which autoimmune diseases are ameliorated (or exacerbated) by an FcRn deficiency in a variety of autoimmune diseases. The results will suggest the diseases in which increased serum IgG concentrations are deleterious or protective. In doing so, it should define the autoimmune diseases that might be amenable to anti-FcRn therapeutic strategies. While FcRn protein is detected only at low levels in healthy adult mice, our new results indicate that FcRn protein increases substantially as mice develop SLE. Aim 2 will thus determine whether an increased level of FcRn expression contributes to autoimmune disease. These results should provide important insights into why FcRn is upregulated and whether FcRn upregulation is a major factor in establishing and maintaining hypergammaglobulinemia. While the IgG conserving function of FcRn is well established, the difficulties in monitoring FcRn in vivo have impeded the resolution of major issues concerning its in vivo biology. To determine the tissue sites in which FcRn expresses and operates to protect IgG from catabolism under normal and autoimmune situations, Aim 3 will thus employ Cre-Lox technology to replace the normal FcRn gene with an FcRn-GFP fusion construct. The expression of this construct under normal regulation and under tissue specific regulation will clarify the anatomy of FcRn-

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mediated protection of IgG, and, more generally, will facilitate many other aspects of investigation into the physiology of FcRn. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •

Project Title: CLINICAL RESEARCH COMPONENT Principal Investigator & Institution: St Clair, Eugene W.; Associate Professor; Duke University Durham, Nc 27706 Timing: Fiscal Year 2003; Project Start 01-SEP-2003; Project End 31-AUG-2008 Summary: The Clinical Research Component, an integral part of the proposed Autoimmunity Center of Excellence, shares with the Basic Research Component an overall goal of advancing the treatment of autoimmune disease through B cell targeted approaches. Dr. E. William St.Clair, the Principal Investigator of the proposed Center, will direct the Clinical Research Component. Duke University Medical Center has a wealth of superb clinical investigators and resources to support in excellence the development and implementation of clinical trials. To meet the requirements set forth in the Request for Applications, we have assembled a talented group of experienced clinical investigators with expertise across a broad spectrum of autoimmune disease. Each of the investigators is a clinical expert in the conduct of clinical trials, with access to the relevant patient populations. These investigators include Drs. St.Clair, Sandy, Pisetsky, Hall, Schanberg, Ortel, Onken, and Sanders, representing expertise in rheumatoid arthritis (RA), systemic lupus erythematosus (SLE), autoimmune blistering diseases, juvenile arthritis and pediatric SLE, anti-phospholipid antibody syndrome, imflammatory bowel disease, and myasthenia gravis. All of these investigators have documented their commitment to support the research activities within the Center. We propose two clinical trials on the cutting-edge of therapeutics for autoimmune disease. One of the trials will investigate the effects of a novel anti-CD22 monoclonal antibody (mAb) in RA. CD22 is expressed on the surface of mature B cells and acts as both a positive and negative regulator of B celt function. Mechanistic studies will determine the extent to which this intervention changes the phenotype and signaling properties of B cells, paralleling the mouse studies ofanti-CD20 and anti-CD22 mAb described in Basic Research Project 1. The other trial will examine the clinical benefits of infliximab therapy (chimeric anti-TNF mAb) for pemphigus vulgaris. Pemphigus vulgaris is a rare, autoimmune blistering disease in which excessive TNFalpha production and antibodies to desmoglein-3 play important roles in the pathogenesis of the skin lesions. The mechanistic studies for this trial will determine if the neutralization of TNFalpha interferes with the mobilization of immature B cells from the bone marrow and selection of the autoreactive B cell repertoire, a hypothesis also addressed experimentally in Basic Research Project 2. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen

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Project Title: DISEASE

CONFERENCE--PATHOGENESIS

OF

NEUROIMMUNOLOGIC

Principal Investigator & Institution: Brosnan, Celia F.; Professor; Marine Biological Laboratory 7 Mbl St Woods Hole, Ma 02543 Timing: Fiscal Year 2001; Project Start 01-JUL-2001; Project End 30-JUN-2005 Summary: (provided by applicant): This application represents a request for continued support for a short course entitled "Pathogenesis of Neuroimmuno1ogical Diseases" offered at the Marine Biological Laboratory, Woods Hole, MA. It is anticipated that the course will be offered every other year for 2001, 2003 and 2005. The course offers a

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Myasthenia Gravis

comprehensive survey of current concepts in the pathogenetic mechanisms involved in a series of neurologic and psychiatric diseases, and includes a faculty, numbering about 40, composed of basic scientists and physician scientists with a wide area of expertise. The two week program of lectures will describe the application of genetic, molecular, and cell physiologic concepts and techniques in current use in immunology and neurophysiology to the analysis of the pathogenesis of the better known neurologic diseases thought to have an immune basis. Lectures in Immunopathologic Mechanisms will deal with: neural antigens and with the cellular components of the nervous and immune systems, their genetic control, and their interactions; with antigen processing and presentation, immunogenesis, and tolerogenesis; with cytokines, complement, neuroendocrine, and "psychoneuroimmunologic" relationships; and with the role of viruses in immunopathologic disorders of the nervous system. Primarily AntibodyMediated "autoimmune" disorders will include: myasthenia gravis, Guillain Barre disease, and paraneoplastic disorders. Primarily Cell-Mediated 'autoimmune" disorders will include: acute post-infectious encephalomyelitis, multiple sclerosis, and chronic inflammatory diseases of the eye, the autonomic nervous system, and muscle. Additional lectures will deal with Persistent Viral Infections of the nervous system and chronic inflammatory disorders of the CNS related to immune dysfunction, such as: HTLV- 1-associated myelopathy, progressive multifocal leukoencephalopathy, SSPE, nervous system manifestations of AIDS, and Alzheimer's disease. The presentations will deal with mechanisms underlying disease process and lesion formation, and with their physiologic consequences. The sessions will be supplemented by demonstrations of patients with typical neuroimmunologic disease at health care institutions and of relevant viral and autoimmune models in animals. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •

Project Title: CONGENITAL MYASTHENIC SYNDROMES Principal Investigator & Institution: Engel, Andrew G.; Consultant in Neurology; Mayo Clinic Rochester 200 1St St Sw Rochester, Mn 55905 Timing: Fiscal Year 2002; Project Start 01-MAY-1977; Project End 30-APR-2007 Summary: The broad aim of this proposal is to examine the neurobiology of congenital myasthenic syndromes (CMS). The CMS are heterogeneous and disabling disorders in which the safety margin of neuro-muscular transmission is compromised by one or more specific mechanism(s). The CMS are not uncommon but are seldom diagnosed or treated correctly. Clinical, morphologic and electrophysiologic analysis can determine whether a CMS is presynaptic, synaptic, or postsynaptic in origin and point to a defect in an endplate (EP) specific protein, such as the acetylcholine receptor (AChR), acetylcholinesterase (AChE), or choline acetyltransferase. The CMS are investigated by: (1) Clinical assessment, including electromyography and tests for anti-AChR antibodies; (2) morphologic assessment, including immunocytochemical localization of AChR, AChE, and other EP- specific proteins, estimate of the number of AChR per EP, ultrastructural analysis of the EP, and evaluation of the density and distribution of AChR on the junctional folds; (3) electrophysiologic assessment, consisting of conventional microelectrode studies of EP potentials and currents, estimates of parameters of quantal release, and evaluation of AChR channel kinetics through single channel patch-clamp recordings; (4) mutation analysis when the preceding studies point to an EP- specific protein; and (5) expression studies using genetically engineered mutants. (6) When CMS patients identified at centers in the US or abroad cannot come to Mayo but the available data point to a candidate gene or molecule, we still search for mutations; if we detect mutation(s), we confirm pathogenicity as in (5) above. The

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proposed studies important for diagnosis and prevention of the CMS, for investigating disease pathophysiology, for developing strategies for therapy, and for gaining insights into structure-function relationships of EP-specific proteins. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •

Project Title: DEVELOPMENT OF IONIC CHANNELS Principal Investigator & Institution: Dryer, Stuart E.; John and Rebecca Moores Professor; Biology and Biochemistry; University of Houston 4800 Calhoun Rd Houston, Tx 77004 Timing: Fiscal Year 2001; Project Start 15-MAR-1995; Project End 14-FEB-2002 Summary: (from applicant's abstract) The intrinsic electrophysiological properties of a neuron determine how that cell will transmit signals and process information. Therefore it is critical that developing neurons acquire electrophysiological properties appropriate for their normal function in mature neural networks. Compared to other developmental events, relatively little is known about this process. This research will examine the developmental expression of Ca-activated K+ currents (IK[ca]) in chick ciliary ganglion (CG) neurons. IK[ca] is an important current because it contributes to regulation of resting membrane potential, spike waveform, and repetitive spike discharge, and because it can be modulated by neurotransmitters in many types of cells. In CG neurons, the normal developmental expression of IK[ca] requires interactions with target tissues in the eye, and with preganglionic nerve terminals. This research will test the hypothesis that the target-derived factor regulating IK[ca] is an isoform of transforming growth factors (TGF-beta), and that the preganglionic nerve terminal-derived factor is an isoform of beta-neuregulin. It is further proposed that these factors induce posttranslational modifications that confer Ca2+-dependence onto preexisting IK[ca] channels; that these two factors produce synergistic effects; and that the simultaneous actions of both factors is required to achieve normal expression of a functional IK[ca]. The role of target-derived TGF-beta will be established by means of specific inhibitors, neutralizing antibodies and intraocular injection of antisense oligonucleotides. The biophysical properties of single IK[Ca] channels induced by beta-neuregulin and TGFbeta treatment, and the temporal nature of their individual and combined actions, will be examined with a view towards determining the molecular basis of the actions of these growth factors. Inappropriate expression of ionic channels could lead to a number of neurological and developmental abnormalities. Moreover, damaged neurons exhibit changes in ionic channel expression similar to changes that take place in developing neurons. TGF-beta and beta-neuregulins have been proposed as potential therapeutic agents for treatment of Parkinson's disease, stroke, multiple sclerosis, myasthenia gravis, and other neurological diseases. Thus, it is important to learn how these agents affect the functional properties of vertebrate neurons. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen

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Project Title: DYNAMICS OF ACHE IN NORMAL AND MUTANT SYNAPSES Principal Investigator & Institution: Akaaboune, Mohammed; Molecular/Cell/Develop Biology; University of Michigan at Ann Arbor 3003 South State, Room 1040 Ann Arbor, Mi 481091274 Timing: Fiscal Year 2003; Project Start 30-SEP-2003; Project End 30-JUN-2007 Summary: (provided by applicant): The goal of this proposal is to study the dynamics (the removal, the insertion, and the mobility) of the extracellular matrix acetylcholinesterase (ACHE) in the synaptic cleft in the neuromuscular junction (NMJ)

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of living mice. In particular, we will study what factors that might regulate its dynamic behavior. We will focus on the role of synaptic activity, a key molecule in the extracellular basal lamina (laminin alpha 4) and in postsynaptic proteins, and the dystrophin glycoprotein complex. Our second goal is to investigate whether the metabolic stability of acetylcholine receptors (AChR) in the postsynaptic membrane is influenced by AChE function. Finally we will study changes in synaptic dynamics of both AChE and AChR at a single synapse. To address these questions we will use the NMJ as a model of synapses in vivo. The use of high-resolution confocal microscopy, in vivo fluorescence imaging assay and the photo-unbinding technique that we developed recently will help us to better understand how the densities of AChE and AChR are maintained and regulated in living synapses. By investigating such questions, we should gain a better understanding of how synaptic alterations occur in less accessible central synapses. Additionally many neuromuscular diseases have either primarily or secondarily major impact on the density of AChRs and AChEs at neuromuscular junctions such as myasthenia gravis. By understanding the regulation of these key synaptic molecules, we expect to define new approaches that might be used to develop effective therapies for these devastating diseases. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •

Project Title: ENHANCE IMMUNE RECONSTITUTION OF T LYMPHOCYTES AFTER SCT Principal Investigator & Institution: Haynes, Barton F.; Frederick M. Hanes Professor & Chair; Duke University Durham, Nc 27706 Timing: Fiscal Year 2002; Project Start 01-MAY-2002; Project End 30-APR-2006 Summary: The thymus plays an important role in maintaining the peripheral T cell pool in human adults and in immune reconstitution after stem cell transplantation. However, no treatment strategy is currently available to augment postnatal human thymus output following stem cell transplantation in a manner analogous to G-CSF for augmentation of myeloid reconstitution. The lack of an assay for postnatal thymic function has also hindered the study of modalities that might stimulate renewed or augmented thymopoiesis in vivo., These numbers of stem cells to repopulate the human immune systems in adults, thus making allogeneic transplantation using cord blood stem cells available to a wide variety of recipients. Measurement of T Cell Receptor Delta (TCRD) signal joint (sj) T cell receptor excision circles (TRECs) has been used to quantify and monitor human thymic output following highly active anti-retroviral therapy (HAART) in HIV-infected patients. We have recently used the TREC assay to monitor human thymic output before and after thymectomy for myasthenia gravis (MG) and to monitor immune reconstitution following thymus transplantation for DiGeorge Syndrome and bone marrow transplantation for Severe Combined Immune Deficiency Syndrome (SCID). No TREC assay was previously available for murine studies. We have developed a TCRD sjTREC assay to monitor thymic output in mice, and have begun to apply it to study murine postnatal thymic function. In the specific aims below, we will combine (molecular) sjTREC, histologic, and phenotypic analysis of T cells and thymus tissues to devise and evaluate new strategies for enhancing T cell immune reconstitution in the setting of stem cell transplantation. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen

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Project Title: EXPERIMENTAL AUTOIMMUNE AUTONOMIC NEUROPATHY Principal Investigator & Institution: Vernino, Steven A.; Mayo Clinic Rochester 200 1St St Sw Rochester, Mn 55905

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Timing: Fiscal Year 2001; Project Start 19-FEB-2001; Project End 31-JAN-2006 Summary: (Adapted from the Applicant's Abstract): The discovery of acetylcholine receptor (AChR) antibodies in patients with myasthenia gravis (MG) led to recognition of other IgG-mediated neurologic diseases and had practical implications for serological diagnosis and immunomodulatory therapy of MG, the Lambert-Eaton myasthenic syndrome and other disorders. Our recent serological studies have implicated autoantibodies against the neuronal AChR in autonomic ganglia as the cause of acquired severe dysautonomia in some patients. In addition, these ganglionic AChR antibodies are proving to be useful serological markers of subacute autonomic neuropathy. Serum ganglionic AChR antibody levels correlate significantly with the severity of autonomic dysfunction, and a reduction in antibody level correlates with improvement in clinical and laboratory indices of autonomic function. As part of a program to nurture the career of a young neurologist clinician-investigator, we propose to develop and study animal models of autoimmunity against the ganglionic AChR to establish the etiology of human subacute autonomic neuropathy. Initial rodent experiments will examine indices of ganglionic synaptic transmission in vitro and autonomic function in vivo. Using these studies as a baseline, subsequent experiments will evaluate the effects of passive ganglionic AChR antibody transfer and active immunization on autonomic function in animals. This project is the first step toward complete understanding of a serious human neurologic disease and lays the foundation for investigating other disorders of neuronal cholinergic transmission. Novel therapeutic trials are anticipated as a clinical translational outcome of this research. The proposed project involves close interaction with established mentors at an institution with a record of excellence in clinically-relevant basic science research. The candidate has already shown potential for independent patient-based laboratory research, and with further training will develop a successful independent research program including clinically based laboratory research and translational clinical research in neurology. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •

Project Title: EXPRESSION AND STRUCTURE OF THE ACETYLCHOLINE RECEPTOR Principal Investigator & Institution: Wang, Zuo-Zhong; Neurobiology; University of Pittsburgh at Pittsburgh 350 Thackeray Hall Pittsburgh, Pa 15260 Timing: Fiscal Year 2001; Project Start 03-DEC-1998; Project End 30-NOV-2003 Summary: Our long-term goal is to elucidate the molecular mechanisms underlying ligand-neurotransmitter receptor interactions utilizing the muscle nicotinic acetylcholine receptor (AChR) as a model. Although the AChR was first purified and cloned nearly 20 years ago, detailed structural information of this protein is still very limited. This is mainly due to the inherent difficulty of crystallizing membrane proteins. Hence, or main objective is to express large quantities of soluble, N-terminal extracellular domains of the AChR alpha and delta subunits, and to determine their 3-dimensional structure. This domain, in the alpha subunit, comprises almost half the subunit mass and contains the binding site for alpha-bungarotoxin (alpha-BuTx) as well as the so-called major immunogenic region (MIR). This region is the target of autoimmune antibodies in myasthenia gravis. In addition, this domain contains the structural information for assembly with the delta subunit to form alphadelta heterodimers which can bind cholinergic ligands, such as acetylcholine (ACh) and d-tubocurarine (dTC). The specific aims of this proposal are: 1) to identify a minimal soluble sequence on the alpha subunit that can fold to form an alpha-BuT binding site and the MIR; 2) to define the minimal domains on the alpha and domain subunits that can form a soluble heterodimer with a

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Myasthenia Gravis

high affinity ACh-binding site. Properly folded alpha N-terminal domain and the alphadelta heterodimer will be expressed as secretory proteins in yeast, and purified to homogeneity; 3) to determine the 3D solution structure of the alpha extracellular domain in free form and in complex with alpha-BuTx using multi-dimensional NMR. Also, structural elements on the alphadelta heterodimer interaction with ACh and dTC will be delineated using transferred NOE; 4) to crystalize the alphadelta heterodimerACh complex and the MIR-autoimmune antibody complex in order to study their structure using x-ray diffraction methods. Completion of this project will allow us to solve the long-sought structure of the ligand-binding sites of the AChR. It will also provide insight into the common structural elements that determine the function of other ligand-gated ion channels, such as the GABA, glycine and 5-HT/3 receptors. As these proteins play important roles in the pathogenesis of pain, mental illness and other common disorders such as epilepsy and stroke, information on their structure is essential for the rational drug design for more selective therapeutic agents. Finally, techniques to be developed through this work should facilitate future structural studies of these and other ligand-gated ion channels. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •

Project Title: GENE THERAPY FOR TOLERANCE TO MULTIPLE EPITOPES Principal Investigator & Institution: Tschetter, Jolynne; Tolergen, Inc. 5719 Wilson Ln Bethesda, Md 20817 Timing: Fiscal Year 2001; Project Start 30-SEP-2001; Project End 29-SEP-2003 Summary: (provided by applicant): TolerGen, Inc. is an entrepreneurial biotechnology company established in 1997 devoted to the development and commercialization of novel therapies for inducing and maintaining epitope-specific immune tolerance using genetic engineering strategies. Based on the hypothesis that self immunoglobulins and B-cell antigen presentation would be highly tolerogenic, we have engineered retroviral constructs containing multiple epitopes in frame at the N-terminus of a murine IgG1 H chain. Recipients of bone marrow or peripheral B cells transduced with these vectors are tolerant to the expressed genes. Data in two experimental autoimmune models (uveitis and EAE) are promising in that significant clinical efficacy has been achieved. It is not clear, however, what the practical limits are for the antigenic epitopes employed in this platform and the best vectors to deliver our gene therapy for tolerance. Since the acetylcholine receptor (AChR) is a major target for the immune response in the autoimmune disease, myasthenia gravis, we plan to synthesize a series of overlapping 100-mers of the alpha subunit of the AChR and full length AChR on the IgG scaffold. Our first goal is to determine whether these antigens can be effectively presented by transduced LPS blasts to induce tolerance to multiple AChR epitopes in our gene therapy model. Next, we will apply these to an FIV-based non-primate lentivirus vectors for expression and eventual tolerance induction as an important step toward future clinical trials in humans. The accomplishment of these two aims will enable us to design a specific product, an AChR or multimeric epitope-linked Ig vector, that can be used therapeutically to modulate autoimmunity in myasthenia gravis. Our approaches will allow us to predict that tolerance to larger molecules can be achieved via this technique and that the host can then present the relevant epitopes in a haplotype-specific manner for tolerance induction in autoimmune diseases, as well as for proteins of gene therapeutic interest. PROPOSED COMMERCIAL APPLICATION: NOT AVAILABLE Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen

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Project Title: GENE MYASTHENIA

TRANSFER

FOR

SPECIFIC

Studies

17

IMMUNOTHERAPY

OF

Principal Investigator & Institution: Drachman, Daniel B.; Professor; Neurology; Johns Hopkins University 3400 N Charles St Baltimore, Md 21218 Timing: Fiscal Year 2001; Project Start 09-FEB-2001; Project End 31-JAN-2005 Summary: (adapted from applicant's abstract): This is a proposal to develop and apply a unique and powerful new gene transfer strategy for specific immunotherapy of myasthenia gravis (MG). Ideally, therapy of MG should specifically inhibit the autoimmune response to the autoantigen, acetylcholine receptor (AChR), without otherwise interfering with the immune system. Because the antibody response to AChR is T cell dependant, elimination of the AChR-specific T cells interrupts the autoimmune disorder at a pivotal point, resulting in clinical benefit. This requires elimination of virtually all AChR-specific T cells. However, the marked heterogeneity of T cell responses to AChR in humans and in experimental animals presents a challenge in designing specific treatment capable of eliminating the entire repertoire of AChRspecific T cells. The investigator's targeting strategy is based on the fact that a myasthenic individual's own antigen presenting cells (APCs) can present AChR epitopes to that indivudual's entire repertoire of AChR specific T cells. They have adapted a method that induces the APCs to process and present AChR by inserting a cDNA construct that encodes the key immunogenic domain of the AChR flanked by signals that induce the APCs process and present it. These APCs target AChR-specific T cells highly effectively. In order to eliminate the targeted T cells, they utilize Fas ligands as a "warhead." When FasL interacts with Fas, which is abundantly expressed on activated T cells, it induces apoptosis and death of the T cells. Insertion of the gene for FasL in APCs induces them to express FasL, which effectively kills Fas-expressing target cells. It is essential to protect these APCs, which would die by FasL- induced "suicide," because they also express Fas. To protect these APCs, they insert a 3rd gene for a truncated form of FADD, which acts as a dominant negative inhibitor of Fas-mediated cell death, into the APCs. To insert all 3 genes simultaneously into APCs ex vivo, they have developed a vaccinia virus vector (vvv), which carries all 3 genes. This vaccinia vector can transfer multiple genes simultaneously, inducing high level production of the gene encoded proteins. When it is attenuated (by treatment with psoralen and UV light) the vvv does not replicate but does direct expression of the gene products. Finally, the expression of FasL directed by their vvv system should confer protection against an immune attack by the host's immune system on the virus vector itself. They now propose to optimize the system and develop it in two animal models: (1) experimental MG, including a new transgenic myasthenic mouse model; and (2) a transgenic mouse model of hemaglutinin (HA) sensitivity. The experiments described in the present proposal will develop this novel strategy in experimental animals, both for prevention and for treatment of EAMG. This method is designed to be suitable for treatment of human autoimmune diseases. When optimized in experimental animals, it will be adaptable for treatment of patients with MG and other autoimmune diseases. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •

Project Title: GENETICS OF AUTOIMMUNE POLYENDOCRINE SYNDROME II Principal Investigator & Institution: Spritz, Richard A.; Professor and Director; University of Colorado Hlth Sciences Ctr P.O. Box 6508, Grants and Contracts Aurora, Co 800450508 Timing: Fiscal Year 2001

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Myasthenia Gravis

Summary: Autoimmune polyendocrine syndrome type II (APS-II) is characterized by the co-occurrence of two or more of various autoimmune disorders in individuals, and often also in their family members, most typically Addison's disease, autoimmune thyroid disease (Graves' disease and hypothyroidism), type I diabetes mellitus celiac disease, hypogonadism, vitiligo, alopecia, pernicious anemia, and myasthenia gravis, but in some families may also include lupus erythematosis, juvenile rheumatoid arthritis, multiple sclerosis, and other disorders. Our analyses strong indicate that autoimmunity in APS-II is controlled by a non-MHC gene in the context of a susceptible HLA genotype. We propose to map this non- MHC APS-II gene, determine its role in different clinical subtypes of APS-II, determine which autoimmune manifestations of APS-II are accounted for by this 2-locus model, and ultimately to identify the non- MHC APS-II gene. Our approach is to identify and analyze large APS-II pedigrees to define clerical heterogeneity that may reflect underlying genetic heterogeneity. We have carried out a series of large preliminary clinical surveys identifying three distinct groups of APS-II families in whom specific autoimmune disorders appear to occur as autosomal dominant traits; families with multiple cases of Addison's disease and other autoimmune disorders, families with multiple cases of vitiligo and other autoimmune disorders, and families with adult-onset type 1diabetes mellitus and other autoimmune disorders. In the multiplex Addison's disease families, we have identified specific HLA genotypes that appear to be necessary but not sufficient for the occurrence of disease. Given a susceptible HLA genotype, the occurrence of Addison's disease in these families appears to be determined by an autosomal dominantly inherited locus outside the MHC. We will map this non-MHC APS-II locus by an initial 10-cM genome screen to identify a candidate region of linkage, we will then refine this localization using additional families and additional markers, to the point of constructing a physical map of the region, and we will eventually identify the non-MHC APS-II susceptibility gene. We also plan to collect samples from vitiligo/APS-II and diabetes/APS-II families and to determine which of the various autoimmune manifestations in these families are accounted for by this gene. Definition of genes that predispose to various forms of APSII will greatly enhance our understanding of the genetics and causation of autoimmunity in general. The occurrence of lupus erythematosis, juvenile rheumatoid arthritis, and multiple sclerosis in some families with APS-II suggests that the identification of APS-II genes may also shed light on the pathogenesis of these autoimmune disorders. In the long run, identification of genes and corresponding gene products that are involved in these autoimmune disorders will undoubtedly open up new avenues of approach to their treatment and even prevention. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •

Project Title: GENETICS OF LUPUS-RELATED AUTOIMMUNITY IN HUMANS Principal Investigator & Institution: Moser, Kathy L.; Assistant Professor; Medicine; University of Minnesota Twin Cities 200 Oak Street Se Minneapolis, Mn 554552070 Timing: Fiscal Year 2001; Project Start 20-SEP-1999; Project End 31-AUG-2003 Summary: The possibility that different autoimmune phenotypes might share particular genetic linkages has been bolstered by a meta-analysis of the available data (Becker, et al, PNAS 95:9979-9984, 1998). In addition, our collection of pedigrees multiplex for systemic lupus erythematosus (SLE), as a clinical disease, contain many members who do not have lupus, but who do have autoimmune findings. Examples include lupusrelated positive serology and other disorders thought to be autoimmune in origin such as myasthenia gravis, rheumatoid arthritis, scleroderma, Sjogren's syndrome, psoriasis, and diabetes. Recently, we published the results of a genome scan using clinical lupus as

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a phenotype (Moser, et al. PNAS 95:14869-14874, 1998). In 94 pedigrees studied, there are 223 confirmed SLE affecteds and 594 family members, 17 percent of who report the presence of another autoimmune disorder and over 30 percent with positive autoimmune serology. In classic work, Bias and coworkers (Am J Hum Genet 39:584602, 1986) have shown that pedigrees ascertained on lupus and evaluated using humoral autoimmunity as an intermediate phenotype segregate this trait in an autosomal dominant pattern. We propose to use our now larger collection of pedigrees multiplex for SLE as a basis from which to seek evidence for the predicted autosomal dominant linkage as well as for other genetic effects. We will use our currently available collection of 173 pedigrees containing 1300 individuals to: 1) evaluate for a LupusRelated Autoimmune (LRA) phenotype, 2) seek linkage, and 3) perform fine mapping in regions providing evidence for linkage. Identification of genes that govern the propensity to develop autoimmunity has potential to provide important insight into mechanisms of etiology and pathogenesis that are common among multiple autoimmune diseases. Understanding these underlying pathological events will lead towards new opportunities for development of more effective mechanism-based therapeutic strategies. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •

Project Title: IMMUNOTHERAPY OF MYASTHENIA GRAVIS Principal Investigator & Institution: Blalock, J Edwin.; Physiology and Biophysics; University of Alabama at Birmingham Uab Station Birmingham, Al 35294 Timing: Fiscal Year 2001; Project Start 01-APR-1997; Project End 31-MAR-2003 Summary: (Adapted from Investigator's abstract): Myasthenia gravis (MG) and experimental autoimmune myasthenia gravis (EAMG) are caused, in part, by the production of T-cell-dependent, autoantibodies against the main immunogenic region (MIR), amino acids 61-76, of the acetylcholine receptor (AChR) alpha-chain. In this application, the investigators describe a means to achieve the long sought therapeutic goal of specifically correcting aberrant immune responses in autoimmune diseases such as EAMG. Specifically, epitope sequence information, together with new knowledge of the role of the precise pattern of amino acid hydropathy in protein and peptide shape or structure, allows one to construct peptides which presumably assume shapes or structures complementary to disease-associated epitopes. As a consequence, vaccination with the novel peptides (termed complementary peptides) leads to the production of anti-idiotypic (Id) and anti-clonotypic antibody (Ab) whose combining sites are complementary to and therefore reactive with antigen (Ag) receptors on disease epitope specific B-cells and T-cells. This application is directed towards the study of two such peptides, denoted RhCA 67-16 and RhCA 611-001, designed to be complementary to the MIR and the dominant Lewis rat T-cell epitope (alpha-chain residues 100-116) of the Torpedo AChR, respectively. Both peptides are effective vaccines which prevent EAMG by lowering levels of AChR Ab. However, RhCA 67-16 Ab seems to act at the level of the AChR 61-76-specific B-cell, while RhCA 611-001 Ab acts on AChR 100-116-specific Tcells. Thus, the overall goal of this application is to expand on these provocative findings by evaluating the nature and contribution to disease of Id Abs and T-cells recognized by Ab to AChR complementary peptides. This will be accomplished through the following specific aims: 1. What is the relative contribution to EAMG of AChR-specific Ab that bear an Id recognized by a MAb (termed TCM 240) against RhCA 67-16? 2. What is the frequency, sequence and specificity of TCM 240 Id-bearing Ab? 3. Is the T-cell receptor (TCR) on AChR 100-116-specific T-cells recognized by MAb (termed CTCR8) against RhCA 611-001? 4. Does administration of polyclonal anti-RhCA 611-001 Ab or CTCR8

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Myasthenia Gravis

lower AChR Ab levels and prevent EAMG? 5. Is there restricted usage of TCR by AChR 100-116 specific T-cells recognized by CTCR8? 6. Can EAMG-associated T-cells of other specificities be identified with complementary peptides to different AChR T-cell epitopes? Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •

Project Title: INTRATHYMIC PATHOGENESIS OF MYASTHENIA GRAVIS Principal Investigator & Institution: Levinson, Arnold I.; Professor; Medicine; University of Pennsylvania 3451 Walnut Street Philadelphia, Pa 19104 Timing: Fiscal Year 2001; Project Start 01-JUL-2001; Project End 31-MAY-2005 Summary: (provided by applicant): The thymus has been considered to play an important role in the pathogenesis of myasthenia gravis (MG), a prototypic autoimmune disease characterized by skeletal muscle weakness. However, its role still remains a mystery. The expression of the autoantigen, acetylcholine receptor (AChR), in the thymus has raised the hypothesis that immunity to this self-protein may be initiated or perhaps perpetuated in this organ. The overall objective of this proposal is to enhance our understanding of mechanisms by which an immune response to this self-antigen might be engendered in the thymus. The hypothesis to be tested is that an inflammatory reaction to an irrelevant antigen in the thymic medulla leads to augmented entry into the thymus of peripheral T cells. Included amongst these thymic immigrants are T cells with low affinity receptors for AChR. Such T cells become activated in the local milieu of the inflamed thymus where they engage upregulated expression of AChR, MHC antigens and co-stimulatory molecules on thymic stromal cells. The Specific Aims of this project are to 1) further characterize our murine model of thymic inflammation, 2) determine if peripheral T cell immigration to an inflamed thymus is enhanced relative to a normal thymus, 3) determine if thymic T cell immigrants are activated by a neo-selfantigen expressed in an inflamed thymus, and 4) determine if AChR specific T cells migrate to an inflamed thymus, become activated by locally expressed autoantigen and initiate a myasthenic syndrome. A retroviral based vector system will be used to induce thymic inflammation by targeting the expression of an irrelevant antigen, betagalactosidase, in the thymic medullary epithelium of mice immunized to this protein. These studies provide a novel approach to elucidate the role of the thymus in the pathogenesis of MG. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen

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Project Title: INTRAVENOUS MYASTHENIA GRAVIS

IMMUNOGLOBULIN

IN

GENERALIZED

Principal Investigator & Institution: Thornton, Charles; University of Rochester Orpa Rc Box 270140 Rochester, Ny 14627 Timing: Fiscal Year 2001 Summary: The major objective of this study is to determine if intravenous immunoglobulin is an effective therapy for myasthenia gravis. This will be established by performing a double-blind, placebo-controlled study in which MG patients will receive IVIG or albumin. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen

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Project Title: INVESTIGATING IL-6 EXPERIMENTAL MYASTHENIA GRAVIS Principal Investigator & Institution: Christadoss, Premkumar; Microbiology and Immunology; University of Texas Medical Br Galveston 301 University Blvd Galveston, Tx 77555 Timing: Fiscal Year 2002; Project Start 30-SEP-2002; Project End 29-SEP-2003 Summary: (provided by applicant): Studies suggest a pivotal role for IL-6, TNF, and IL18 in development of experimental autoimmune myasthenia gravis (EAMG), because a dramatic suppression of clinical EAMG was observed in IL-6, TNF receptor p55 p75, or IL-18 gene KO mice in the B6 background. The precise cellular and molecular mechanisms by which IL-6, TNF, and IL- 18 contribute to EAMG pathogenesis are not known. The central hypothesis is that IL-6 contributes to EAMG pathogenesis by activating acetylcholine receptor (AChR)-specific T and B cells and germinal center (GC) formation, promoting secondary anti-AChR IgG antibodies and activation of the C3 component of complement. The immunopathological and clinical effects will be evaluated by in-vivo IL-6 administration in B6 and IL-6 KO mice during primary and/or secondary immunizations with AChR. Clinical and immunopathological signs of EAMG will be induced in B6 mice by in vivo administration of IL-6 after priming with AChR. AChR-primed LNC will be exposed to IL-6 and its effect on anti-AChR IgM and IgG isotypes will be evaluated. Also, we will examine whether IL-6 and TNF act in concert or regulate one another in mediating EAMG. B7-1 gene-deficient or B7-1 moleculeblocked mice, and B6 mice will be immunized with AChR, and the effect evaluated of B7-1 deficiency or blocking in EAMG development and production of IL-6 and TNF. To prevent EAMG, antibody to IL-6 will be administered with primary and/or secondary immunizations with AChR. To ameliorate established clinical EAMG, antibody to IL-6 will be administered after clinical signs are established. Finally, combination immunotherapy will be performed with high-dose AChR T cell epitope tolerance and IL-6 neutralization in B6 mice. If IL-6 is involved in activating pathogenic AChR-specific B cells, forming GC, and upregulating and activating C3 and if in vivo blocking of IL-6 function induces remission of established clinical EAMG, then IL-6 antagonist could be used in MG therapy. To avoid non-specific immunosuppression by IL-6 antagonists, high-dose AChR T cell epitope tolerance could be given as maintenance therapy after the first course of combination immunotherapy. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen

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Project Title: IVIG IN GENERALIZED MYASTHENIA GRAVIS Principal Investigator & Institution: Barohn, Richard; University of Texas Sw Med Ctr/Dallas Dallas, Tx 753909105 Timing: Fiscal Year 2001 Summary: The major objective of this study is to determine if intravenous immunoglobulin (IVIG) is an effective therapy for MG. This will be established by performing a double-blind, placebo-controlled study in which MG patients will receive either IVIG or albumin. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen

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Project Title: LIGAND BINDING SITES OF THE ACETYLCHOLINE RECEPTOR Principal Investigator & Institution: Pedersen, Steen E.; Associate Professor; Molecular Physiology & Biophysics; Baylor College of Medicine 1 Baylor Plaza Houston, Tx 77030 Timing: Fiscal Year 2001; Project Start 01-JUN-1996; Project End 30-JUN-2003

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Summary: The long-term aim of this research is to understand the regulation of ligandgated ion channels by the binding of neurotransmitters. The particular goal of this application is to understand the importance of charge-charge interactions in the regulation of the nicotinic acetylcholine receptor by the binding of acetylcholine. Specifically, the structure activity relationship of d-tubocurarine to the nicotinic acetylcholine receptor will be examined by analyzing the binding of d-tubocurarine analogs to native and mutated acetylcholine receptors. The role of electrostatic attraction in binding will be examined to determine whether charge- charge attraction governs the rapid rate of acetylcholine binding and contributes to the stabilization of the agonist cation. The channel movements associated with the conformational transition of the acetylcholine receptor will be measured by mutagenesis of residues near the narrow pore of the channel, and by direct measurements of electrostatic potential using fluorescence lifetime spectroscopic methods. The experiments will define functionally relevant components of the receptor structure that contribute to ligand binding, to ion channel structure, and to function. This will improve our understanding of synaptic transmission, a process that underlies the complex phenomena of learning, memory and thought. The skeletal muscle nicotinic acetylcholine receptor (and particularly the extracellular domain) is the target of autoimmune antibodies in the disease Myasthenia Gravis. The neuronal homologues of this protein are involved in nicotine addiction and possibly in Alzheimer's disease. A better understanding of the structure of this protein and especially the acetylcholine binding sites will be important for a full understanding of these ailments and for developing treatments. A fundamental understanding of the binding site stricture will improve rational drug design for this protein while the methodology proposed here may constitute a new paradigm for rational drug design for receptor targets in general. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •

Project Title: MYOCYTE RESPONSES DURING EXPERIMENTAL MYASTHENIA GRAVIS Principal Investigator & Institution: Krolick, Keith A.; Professor; Microbiology and Immunology; University of Texas Hlth Sci Ctr San Ant 7703 Floyd Curl Dr San Antonio, Tx 78229 Timing: Fiscal Year 2001; Project Start 01-JUL-1999; Project End 30-JUN-2003 Summary: Acetylcholine receptors (AChR) are expressed on muscle membranes and are responsible for the reception of signals from nerves that stimulate muscle contraction. Myasthenia gravis (MG) is a neuromuscular disease that is the result of impaired muscle contraction caused by autoantibodies directed at the AChR. However, circulating serum titers of anti-AChR antibodies do not correlate well with disease severity in patients with MG and this lack of correlation has led to the search for other factors which may help determine eventual disease severity. Therefore, it is our hypothesis that muscle is not a passive participant in the development of disease symptoms in MG and, in fact, plays a very important active role by producing immunomodulating factors that can influence the eventual immunopathological impact of the immune system on muscle. The experimental rat model for MG is to be used to test this hypothesis. Accordingly, Lewis rats are to be immunized with purified AChR which results in the production of anti-AChR antibodies and Experimental Autoimmune Myasthenia Gravis (EAMG). Studies will focus on the production of, and responses to, cytokines by muscle cells in rats with EAMG. In this regard, muscle cell lines will be exposed in vitro to selected cytokines in the presence or absence of antiAChR antibodies derived from Lewis rats. The readout will be the induction of myocyte

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products with immunomodulating activities (i.e., cytokines, chemokines, membrane interaction molecules). Similarly, myocyte cell lines derived from a rat strain known to be resistant to the induction of EAMG (Wistar Furth) will be evaluated for differences in myocyte responses that would explain differences in disease susceptibility. Conclusions based on in vitro observations will then be verified in AChR-immunized Lewis rats during the induction phase of the immune response, as well as in rats that have received pre-formed anti-AChR antibodies known to possess differing abilities to induce disease symptoms. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •

Project Title: PIVOTAL REGULATOR IN NEURO-IMMUNE INTERACTIONS Principal Investigator & Institution: Smith, Eric M.; Professor; Psychiatry and Behavioral Scis; University of Texas Medical Br Galveston 301 University Blvd Galveston, Tx 77555 Timing: Fiscal Year 2001; Project Start 01-APR-2000; Project End 31-MAR-2003 Summary: (Adapted from the Investigator's Abstract) The neuroendocrine and immune systems communicate bi-directionally. There are no accepted markers to measure their interactions, or disorders. Neuropeptide hormones and cytokines regulate cells of both systems, but little is known of the intracellular steps between binding to the surface receptors and cellular responses when cytokines and neuropeptides cross systems. The goal of this project is to begin to understand how these multiple signals are integrated at the intracellular level and subsequently alter immune and/or neuroendocrine cell function. Preliminary data suggest that the signal pathways converge and mutually affect the activity of the transcription factor, Nf-kappaB. The project is divided into three aims to investigate whether Nf-kappaB has a pivotal role in the integration of immune and neuroendocrine system signals. 1) Gel shift studies will determine the extent and specificity of neuropeptide hormones and cytokines to affect Nf-kappB in lymphoid and neuroendocrine cells. 2) A luciferase cis-reporter gene system will be used to measure changes in Nf-kappaB activity due to individual and multiple neuropeptide and cytokine signal molecules. Also, specific inhibitors of the Nf-kappaB pathway will be used to determine in a quantitative manner the effect modulating this transcription factor has on in vitro antibody and cytokine production. 3) Finally, studies using a NfkappaB1 gene knockout mouse model will be used for studies of the relative importance of this Nf-kappaB component for neuropeptide and cytokine effects on lymphoid and pituitary functioning. These studies will show the impact and specificity of the NfkappaB pathway in mediating selected neuropeptide and cytokine regulation of immune and neuroendocrine interactions. Inhibitors of Nf-kappaB are being developed, primarily as anti-inflammatory agents. Understanding the role of Nf-kappaB in neuroendocrine-immune interactions may suggest novel markers and therapeutic targets. In turn, these might have great impact for treatment of diseases involving the nervous and immune systems, such as myasthenia gravis or multiple sclerosis. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen

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Project Title: QUALITY CONTROL OF NICOTINIC RECEPTOR ASSEMBLY Principal Investigator & Institution: Green, William N.; Associate Professor; Neurobiology/Pharmacology/Phys; University of Chicago 5801 S Ellis Ave Chicago, Il 60637 Timing: Fiscal Year 2002; Project Start 01-AUG-1997; Project End 31-MAR-2006 Summary: (provided by applicant): Central to the mechanisms that underlie central nervous system function and disease are the different neurotransmitter receptors

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responsible for the rapid signaling between neurons and between nerve and muscle. Like other oligomeric membrane proteins, these neurotransmitter receptor subunits are synthesized and inserted into the membrane of the endoplasmic reticulum (ER) after which the receptor subunits undergo a series of folding and processing steps. The folding and processing steps that occur in the ER transform the individual subunits into mature neurotransmitter receptors before the receptors reach the cell surface. A critical part of the folding and processing that occurs in the ER are the 'quality control' mechanisms that identify, retain and degrade misfolded or misassembled receptor subunits. While much is known about how these receptors function, relatively little is known about how the receptor subunits fold and assemble into functional receptors. The long-term objective of the proposed research is to understand the mechanisms governing the quality control mechanisms in the ER that ensure that only properly assembled and functional receptors are expressed on the cell surface. To achieve this objective, studies will focus on the best-characterized member of this receptor family, the 'muscle-type nicotinic acetyicholine receptor (AChR). The first set of experiments will characterize the interactions between AChR subunits and a specific set of ER resident proteins called chaperone proteins. The second set of experiments will identify the mechanisms involved in the degradation of AChR subunits and determine how subunit degradation affects AChR assembly. The final set of experiments will test whether pathology caused by certain AChR subunit mutations identified in congenital myasthenic syndromes results from defects in AChR assembly or quality control. As the site where nicotine binds in the brain, neuronal AChRs are responsible for nicotine addiction and may play a role in Alzheimer's disease. In addition, the 'muscle-type' AChR is responsible for myasthenia gravis, the autoimmune disease, and many of the congenital myasthenic syndromes both of which cause deterioration of neuromuscular junctions. The level of AChR expression appears to be altered in all three disorders. Since our goal is to elucidate the molecular basis for AChR expression, this proposal should provide insights into certain pathological features of these disorders. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •

Project Title: POTENTIAL

REAL-TIME

MICROSCOPIC

IMAGING

OF

MEMBRANE

Principal Investigator & Institution: Yakovlev, Vladislav V.; Physics; University of Wisconsin Madison 750 University Ave Madison, Wi 53706 Timing: Fiscal Year 2001; Project Start 30-SEP-2001; Project End 31-AUG-2003 Summary: (provided by applicant): This proposal takes advantage of advances in laser technology that make it possible to detect electrical activity in unstained living tissue in a noninvasive manner. The first aim is to build a laser microscope that can detect SH signals generated by focused laser radiation at wavelengths that will minimize the possibility of tissue damage. The optics and data acquisition will be engineered for optimal use in a noninvasive manner and to maximize user-friendliness. The second aim is to evaluate and test the sensitivity of the microscope including its spatial and temporal resolution in detecting action potentials in a classical neurophysiological preparation. The third aim is to use the SH microscope for pilot tests on the functional development of synapses at the developing neuromuscular junction of vertebrates. These studies could provide information about the mechanisms of synapse formation that are not currently possible with other techniques. In addition, the ability to measure activity at the neuromuscular junction in a noninvasive way would have value in a number of clinical applications. Diseases like Myasthenia Gravis, the Muscular Dystrophies, ALS, and Guillain-Barr syndrome affect the activity of nerve and/or

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muscle cells. Optical microscopy could lead to new diagnostic methods and a better understanding of the mechanisms of disease progression. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •

Project Title: REGULATION OF ACETYLCHOLINE RECEPTORS ON MUSCLE Principal Investigator & Institution: Brehm, Paul; Professor; Neurobiology and Behavior; State University New York Stony Brook Stony Brook, Ny 11794 Timing: Fiscal Year 2001; Project Start 01-APR-1989; Project End 31-JUL-2005 Summary: (provided by applicant): The long term interests of my lab have centered on establishing the respective roles of presynaptic calcium channels and postsynaptic cholinergic receptors in neuromuscular transmission. My lab has traditionally relied on use of developing Xenopus neuromuscular junction where, among other advantages, direct cellular analysis of synapse function can be assessed through voltage-clamp of pre and postsynaptic cells. During the past funding period we initiated study of Zebrafish neuromuscular junction, which is functionally similar to Xenopus, but has the additional advantage that behavioral consequences of synaptic dysfunction are directly ascertained. We have identified Zebrafish mutant lines that exhibit locomotory dysfunction resulting from defects in neuromuscular transmission. Two lines exhibit myasthenia gravis-like symptoms in the form of use-dependent fatigue, and the symptoms can be partially rescued by inhibitors of cholinesterase function. Recently, we have shown the defect in one mutant line results from a defective rapsyn gene, and we have succeeded in rescuing the behavioral defect in the mutant fish. Another line with defective synaptic receptor density shows similar progressive weakness but outgrows the behavioral phenotype with age. Both lines exhibit profound synaptic depression at the nerve-muscle junction when compared to wild type animals. We will use these two lines to establish the mechanisms through which alterations in postsynaptic receptor densityleads to the observed synaptic depression. A similar depression can be recorded at Xenopus nerve-muscle synapses where both pre and postsynaptic cells can be voltage clamped. Using this preparation we will determine whether alterations in presynaptic release or postsynaptic receptor desensitization are responsible for synaptic depression. The four specific aims that are proposed merge the collective strengths of in vitro use of Xenopus with behavioral mutants of zebrafish, in order to investigate the mechanisms underlying synaptic plasticity at the neuromuscular junction. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen

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Project Title: REGULATION OF MUSCLE ACETYLCHOLINE RECEPTOR Principal Investigator & Institution: Schmidt, Jakob; Professor; Biochemistry and Cell Biology; State University New York Stony Brook Stony Brook, Ny 11794 Timing: Fiscal Year 2001; Project Start 01-JUL-1985; Project End 29-FEB-2004 Summary: The long-term goal of the research described in this application is the elucidation of how chemical and electrical excitation of the plasma membrane affect gene expression in the neural control of acetylcholine sensitivity. Analysis of acetylcholine receptor regulation is important for a better understanding of neurological and neuromuscular disorders such as Alzheimer's disease or myasthenia gravis. The denervation-induced increase in acetylcholine receptor synthesis rate will be investigated in chick skeletal muscle. It is now known that during differentiation of myogenic cells and upon denervation of mature muscle fibers the transcription of the genes coding for the receptor subunits is activated. Regulatory elements in these genes that mediate stage- and tissue-specific expression will be identified by transfection of

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Myasthenia Gravis

constructs containing sequences of interest as well as suitable reporter genes. The response of transfected cells to drugs that stimulate or block membrane activity will be measured and will permit identification of regulatory elements have already been identified in the upstream flanking regions of the alpha- and delta-subunit genes; future work will focus on other noncoding regions of these genes and on the gamma-subunit. Identification, isolation, and analysis of beta- and alpha-subunit genes will also be undertaken. The initial deletion mutation analysis of cis elements will be followed by more precise delineation using point mutations and footprinting techniques. Eventually, the developmental as well as stimulus-induced coordinated regulation of all subunits will be investigated in vitro and in transgenic animals. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •

Project Title: SARCOLEMMAL ORGANIZATION OF EXTRACULAR MUSCLE Principal Investigator & Institution: Porter, John D.; Professor; Ophthalmology; Case Western Reserve University 10900 Euclid Ave Cleveland, Oh 44106 Timing: Fiscal Year 2001; Project Start 01-FEB-2000; Project End 31-JAN-2005 Summary: Extraocular muscle (EOM) is specifically tailored to serve a diverse repertoire of eye movement control systems. Many aspects of the molecular biology, cell biology, morphology, and function of EOM are very different from the well-describe skeletal muscles of the limb and axial skeleton. Genotype and/or phenoptypic differences in the EOMs may either predispose or protect them in disease. Thus, knowledge of EOM biology is critical in design of theoretical and practical models of eye movements and in preventing or treating disorders. of eye alignment or movement. We currently have almost no knowledge of the cell/molecular substrate for stabilizing the EOM membrane, or sarcolemma, and for formation and maintenance of specializations at the neuromuscular function. What we do know strongly suggests that the transmembrane protein complex that plays these roles in skeletal muscle may exhibit adaptations in EOM. We propose to test the hypothesis that the unique phenotype, and functional properties, of EOM require muscle group-specific adaptations at the level of the intricate complex of proteins that spans the sarcolemma to stabilize during muscle contraction and to organize the neuromuscular junction. First, we will determine the spatial/temporal relationships in maturation EOM and visuomotor systems. Data will establish similarities and differences between EOM and the pattern that has been well described in other muscles. Second, we will investigate the regulatory mechanisms for the specializations in the transmembrane protein complex at neuromuscular junctions in EOM. These studies will allow use to identify the extent to which EOM utilizes general muscle regulatory mechanisms and identify any protein complex in EOM using natural mutant and gene knockout models that generate loss of function in most muscles. Our pilot data establish that EOM responds to loss of components of the transmembrane protein system in ways that other skeletal muscles do not. Proposed studies will begin to understand the molecular mechanisms used by EOM in sarcolemmal organization for the day-to-day function of these novel muscles. An overall knowledge of the properties and regulation of the EOM sarcolemma will be important for understanding and treating ocular motility disorders in myasthenia gravis, congenital fibrosis of EOM, and strabismus. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen

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Project Title: STRUCTURE AND FUNCTION OF THE ACETYLCHOLINE RECEPTOR Principal Investigator & Institution: Sine, Steven M.; Professor; Mayo Clinic Rochester 200 1St St Sw Rochester, Mn 55905 Timing: Fiscal Year 2001; Project Start 01-SEP-1992; Project End 31-AUG-2005 Summary: The long-term aim of our research is to understand how receptors for neurotransmitters operate in health and disease states. We have chosen the acetylcholine receptor (AChR) at the motor synapse to examine the essential function of this class of proteins: binding of neurotransmitter triggering opening of an intrinsic ion channel. Toward understanding this binding-triggering process, we propose to (i) identify residues in a and non-a subunits that stabilize ACh when bound to open and closed states of the channel, (ii) determine how the AChR maintains uniform channel gating kinetics, (iv) determine mechanistic consequences of mutations underlying congenital myasthenic syndromes (CMS), (iv) determine whether conserved residues bounding putative secondary structures in the major extracellular domain contribute to AChR activation and (v) determine structural features of the major extracellular domain of the AChR. The approach combines site-directed mutagenesis and expression in mammalian cells, single channel recording and kinetic analysis, measurements of ligand binding and protein biochemistry. Completion of the proposed studies will advance our understanding of synaptic transmission and drug action at motor endplates, facilitate treatment of neuromuscular disorders such as CMS, while the general findings will provide insight into structure function relationships for other members of the neurotransmitter receptor superfamily. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen

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Project Title: STUDIES USING PURIFIED ACETYLCHOLINE RECEPTORS Principal Investigator & Institution: Lindstrom, Jon M.; Professor; Neuroscience; University of Pennsylvania 3451 Walnut Street Philadelphia, Pa 19104 Timing: Fiscal Year 2001; Project Start 01-SEP-1976; Project End 31-MAR-2004 Summary: (adapted from applicant's abstract) The structure and function of nicotinic acetylcholine receptors (AChRs) are being investigated. Specific immunosuppressive therapy of the autoimmune response to muscle AChRs which occurs in myasthenia gravis (MG) and its animal model, experimental autoimmune myasthenia gravis (EAMG), is also being investigated. One goal is to determine the amount, subunit composition, stoichiometry, and arrangement of neuronal AChR subtypes. This will require expanding our library of subunit-specific monoclonal antibodies (mAbs)and immunoisolating native AChRs. Determining subunit stoichiometry and arrangement will involve expressing cloned AChRs. A second goal is to express a properly assembled, water-soluble extracellular domain of an AChR in amounts suitable for crystallographic studies. We have succeeded in expressing tiny amounts of watersoluble 7 AChR extracellular domains with native ligand binding proteins, but will need to devise methods to increase the efficiency of assembly and increase the amount of protein expressed. This could lead to x-ray crystallographic determination of the structure of an archetypic member of a gene superfamily of wide medical significance. A third goal is to determine the pharmacological and electrophysiological properties of cloned human neuronal AChR subtypes. In addition to expression studies in Xenopus oocytes, this will involve development of a series of permanently transfected cell lines. This should define the functional properties of AChR subtypes, which are the target of nicotine and potential subtype-specific nicotinic drugs now being developed. A fourth

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Myasthenia Gravis

goal is to determine the mechanisms by which chronic exposure to nicotine alters the amounts and functional properties of cloned human neuronal AChRs. These studies should reveal some of the molecular mechanisms by which nicotine produces its and huge medical impact, while also providing insights on possible effects of nicotinic agonists being developed as drugs. A fifth goal is to determine the location of AChR subtypes. This will involve providing our expanded library of AChR-subunit specific mAbs to collaborators. A sixth goal is to develop a practical specific immunosuppressive therapy for EAMG. This will involve inducing tolerance through administration of bacterially-expressed human muscle AChR subunits. It is hoped that this will lead to a specific therapy for MG. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •

Project Title: SUPPRESSION OF CNS AUTOIMMUNE DISEASE BY TH2 CELLS Principal Investigator & Institution: Stohlman, Stephen A.; Professor; Neurology; University of Southern California 2250 Alcazar Street, Csc-219 Los Angeles, Ca 90033 Timing: Fiscal Year 2002; Project Start 01-APR-1996; Project End 30-JUN-2006 Summary: (provided by applicant): Cytokines suppress experimental allergic encephalomyelitis (EAE), a rodent model of central nervous system (CNS) autoimmune disease. This proposal is based on differential CD4+ T cell responses induced in EAE susceptible female and EAE resistant young adult (6 wk) male SJL mice. Female susceptibility is consistent with the increased prevalence of a number of human autoimmune diseases including multiple sclerosis, myasthenia gravis, rheumatoid arthritis and SLE. Thus, the gender-based difference in CD4+ T cell responsiveness in SJL mice provides a unique opportunity to explore in vivo suppression of Th1 cell mediated CNS autoimmune disease via Th2 cells using a single mouse strain. Cotransfer of myelin basic protein (MBP)-specific Th1 effectors and MBP-specific Th2 cells has a dramatic inhibitory effect on both acute and relapse EAE compared to recipients of Th1 effectors only. Similarly, co-transfer of MBP specific Th1 EAE effectors and Th2 cells specific for a non-neuroantigen (Ag) also has a dramatic inhibitory effect on acute and relapse EAE, albeit only in the presence of Ag. The overall goal of this proposal is to define the mechanism(s) of Th2 mediated EAB suppression. Our global hypothesis is that Th2 mediated suppression of CNS autoimmune disease reflects induction of a regulatory/suppressor population of CD4+ T cells, designed Tr cells. A potential role of TGF-Beta in addition to IL- 10, in mediating Th2 induced EAE inhibition is examined. This proposal uses Thy1.1/ThyI.2 disparate donors and recipients, in addition to a recently developed SJL TcR transgenic mouse. Analysis of these donor/recipient combinations, using both in vitro analysis and adoptive transfer of purified populations to inhibit EAE will define the precise phenotype of the effector cells. The issue of derivation of Tr cells is critical to understanding both their biology and therapeutic potential. Therefore, we will determine if the effectors are derived from the donor Th2 population or from the host. Although activated Th1 cells access the CNS, little is known concerning recruitment and/or retention of Tr cells at the site of autoimmunity. Adoptive transfer of effectors derived from either congenic Thy1.1 SJL or Thy1.2 TcR transgenic mice into Thy1 disparate recipients, coupled with analysis of CNS infiltrating cells will determine CNS entry. Mechanism(s) of acute EAE suppression will be examined by determining: 1) the effects of disease inhibition on macrophage influx into the CNS; 2) alterations in the ability of CNS antigen presenting cells to support encephalitogenic Th1 T cells; and 3) the potential activation of neuroAg-specific host derived Th2 cells in the altered CNS environment. Mechanisms of relapse inhibition examined include; 1) CNS retention of effector cells; 2) continued expression of IL- 10 by

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potential CNS APC populations inhibiting activation of host derived encephalitogenic Th1 cells; 3) activation and retention of neuroAg specific Th2 cells specific for encephalitogenic or nonencephalitogenic epitopes, or 4) inhibition of epitope spreading associated with relapses in SJL mice. These experiments will provide information on both the mechanisms of induction of these important regulatory cells, which are critical to both regulation and suppression of autoimmune disease, as well as on their specific role(s) in suppressing CNS autoimmune disease. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •

Project Title: SYNAPTIC HOMEOSTASIS IN DROSOPHILA Principal Investigator & Institution: Marrus, Scott B.; Medicine; Washington University Lindell and Skinker Blvd St. Louis, Mo 63130 Timing: Fiscal Year 2002; Project Start 01-SEP-2002; Project End 31-AUG-2004 Summary: (provided by applicant): Homeostatic mechanisms play an essential role in synaptic function. They are required for the stability of neural networks and play a role in learning and memory. It is suspected that they may compensate for various disease processes, such as myasthenia gravis, and might underlie the efficacy of drugs such as antidepressants. One model system in which homeostasis can be studied is the Drosophila neuromuscular junction. At this synapse, a decrease in the post-synaptic sensitivity to neurotransmitter results in a compensatory increase in pre-synaptic transmitter release. However, little is known about the nature or molecular components of this mechanism. It is not known whether the signal is synapse specific or a more global phenomenon, nor is it known whether this phenomenon occurs only during a critical period of development or also occurs at more mature synapses. The proposed experiments will elucidate these spatial and temporal features of this mechanism. The molecular mechanism will be further probed through the characterization of a novel mutation that disrupts this homeostatic response. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen

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Project Title: SYNTHESIS OF MACROCYCLES STEROIDS CYCLOPENTANOIDS ETC Principal Investigator & Institution: Trost, Barry M.; Professor of Chemistry; Chemistry; Stanford University Stanford, Ca 94305 Timing: Fiscal Year 2001; Project Start 01-JUN-1987; Project End 31-MAY-2002 Summary: Exploring biological phenomena at a molecular level provides the basis of understanding from which new therapeutic agents derive. The ability to construct a defined molecular architecture requires highly selective reactions and reagents to permit the development of effective synthetic strategies. Cyclic compounds have biological activities across a broad spectrum. Furthermore, constraining conformations of mobile molecules by forming rings also frequently enhances biological potency. Thus, a concerted effort to apply new chemical principles being developed in the PI's laboratories to the formation of rings becomes an important objective. In the first phase, a new concept to create macrocycles (rings larger than seven members) may provide a unique opportunity to approach a variety of significant targets. Some examples include the antiinflammatory nine membered macrolides ascidiatrienolides, the antitumor eight membered carbocycles, the shikoccins, and the azocines, FR-99048 and FR-66979, the ten membered macrolactam neuropeptidase inhibitor CGS-25155,the fourteen membered antiviral and antifungal fluviricinines, and the nineteen membered serine protease inhibitors, the cyclotheonamides. In the second phase, a new reactivity mode for

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shuffling protons in totally unconventional methods offers novel approaches to cyclizations. Vitamin D analogues and derivatives represent a most important direction for creation of clinically important therapeutic agents. A new concept for their synthesis based upon novel strategies for asymmetric induction will be pursued. A variation on this methodology may extend the reaction to a facile asymmetric synthesis of either cis or trans fused drimanes and related classes of terpenoids from a common intermediate, a class of compounds that have remarkably broad biological activities including antibacterial, antifungal, antimalarial, antiinflammatory, cytotoxic, and insecticidal. A new class of reactions provides a novel atom economical approach for formation of heterocycles. This invention stimulates exploration of a potentially, greatly simplified strategy to the important food toxin, aflatoxin. The envisioned asymmetric route also may provide a simple protocol for the asymmetric synthesis of physostigmines, one of whose members is a candidate for treatment of myasthenia gravis, glaucoma, and Alzheimer's disease. A third phase examines a new class of cycloaddition reactions to create odd membered rings. Exploring a new class of acceptors in conjunction with a novel class of reactive intermediates creates a conceptual framework to the anthelmintic and antinematodal mold metabolites paraherquamide and marcfortine. An unusual (6+3) cycloaddition may create strategies for the structurally unusual farnesyl transferase inhibitor CP-263,114 and simpler analogues. Ring expansion methods may convert these cores into the taxoid skeleton with appropriate functionality at key points for analog development. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •

Project Title: TARGETED THERAPIES FOR MYASTHENIA GRAVIS Principal Investigator & Institution: Kaminski, Henry J.; Associate Professor; Neurology; Case Western Reserve University 10900 Euclid Ave Cleveland, Oh 44106 Timing: Fiscal Year 2003; Project Start 30-SEP-2003; Project End 31-AUG-2008 Summary: (provided by applicant): Myasthenia gravis (MG) is an antibody-mediated autoimmune disorder, which compromises neuromuscular junction function. The disease may involve skeletal muscle diffusely producing life-threatening weakness, but also produce ocular muscle dysfunction leading to significant visual disability. The final effector mechanism of the myasthenia gravis is the formation of the membrane attack complex of complement at the neuromuscular junction. Complement regulatory proteins normally serve an important role as negative regulators of complement activation. Our preliminary studies and the established disease mechanism strongly support the strategy of enhancing the negative regulation of complement formation as a therapy for myasthenia. This study weaves together the strengths of established investigators in the fields of complement, extraocular muscle biology and physiology, myasthenia gravis pathophysiology, and drug development in order to produce complement inhibitor therapies to target the neuromuscular junction pathology of myasthenia gravis. The investigators propose to achieve this therapeutic goal by first evaluating the complement-mediate pathogenesis at three levels: (a) a global analysis of operative events and mechanisms using genome-wide profiling with DNA microarray, (b) specific measures of complement regulatory transcripts and proteins, and (c) structural/functional measures of skeletal muscle and ocular muscle performance in animal models of experimental autoimmune myasthenia gravis (EAMG) and human MG. The most effective stage of the complement cascade is determined for drug development using transgenic animal models. Our group already has developed complement inhibitors, and additional agents to target the neuromuscular junction will be developed. These will be tested for efficacy and tolerability for use in future clinical

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trials. The goal of the therapy is to provide a drug, which will moderate the severity of acute myasthenic deteriorations and chronically serve as an adjuvant to limit use of immunosuppressants with poor side effect profiles. Because of the ocular muscles' sensitivity to the low-grade autoimmune process of ocular myasthenia, the complement Inhibitor-based therapy developed should be particularly effective for treatment of visual dysfunction. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •

Project Title: TH1 AND TH2 RESPONSES AND MYASTHENIA GRAVIS Principal Investigator & Institution: Infante, Anthony J.; Professor; Pediatrics; University of Texas Hlth Sci Ctr San Ant 7703 Floyd Curl Dr San Antonio, Tx 78229 Timing: Fiscal Year 2001; Project Start 01-APR-1999; Project End 31-MAR-2004 Summary: (Adapted from Investigator's abstract): Experimental autoimmune myasthenia gravis (EAMG) is induced in susceptible strains of mice by immunization with acetylcholine receptor (AchR). Muscle weakness is thought to be entirely mediated by high-affinity IgG autoantibodies, with little participation from cell-mediated effector mechanisms. Recently, strong evidence has been provided that EAMG depends on the production of Th1 cytokines, especially IL-12 and interferon-gamma (IFN-gamma). IFNgamma has been shown to have powerful direct influences on muscle cells in culture, among them upregulation of MHC class II and cell adhesion molecules. The applicant proposes that Th1 cytokines, predominantly IFN-gamma, have a direct action on muscle in vivo, causing increased susceptibility to immune-mediated damage and interference with muscle function, regeneration and repair. Three specific aims are proposed to test this hypothesis. In Aim 1, the investigator will define the role of key Th1 and Th2 cytokines in EAMG, by administration of recombinant cytokines, neutralization of cytokine activity by monoclonal antibodies (mAbs) and studies in cytokine gene knockout mice. The investigator will be particularly interested in whether Th1 and Th2 cytokines are antagonistic or synergistic. In Aim 2, the applicant will purify antibodies made under the influence of various cytokines and assess their pathogenicity by adoptive transfer. The direct effect of cytokines will be measured, individually and in combinations, with and without co-application of autoantibodies to muscle cells grown in culture. These changes in cultured muscle cells will then be correlated with muscle tissue findings in vivo. In Aim 3, a dominant-negative IFN-gamma receptor transgene under the control of tissue specific promoters will be used to confer specific tissue resistance to the actions of IFN-gamma. This hypothesis may show that muscle unresponsiveness to IFN-gamma may confer resistance to EAMG. In addition to providing significant advances in understanding the immunopathogenic basis of MG, such a result could also lead to novel therapy. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen

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Project Title: TRANSMITTER REPLETION: KEY TO PHRENIC-DIAPHRAGM FUNCTION Principal Investigator & Institution: Van Lunteren, Erik; None; Case Western Reserve University 10900 Euclid Ave Cleveland, Oh 44106 Timing: Fiscal Year 2002; Project Start 08-JUL-2002; Project End 31-MAY-2006 Summary: (provided by applicant): Failure of phrenic nerve-diaphragm neuromuscular transmission leads to hypercapnic respiratory failure. This occurs not only in overtly diseased neuromuscular junctions (eg. myasthenia gravis, botulism), but also in normal junctions subjected to high intensity activation during mechanical loading by lung

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disease (eg. COPD) or during exposure to systemic factors such as hypoxia and hypothermia. Neurotransmission requires sufficient prejunctional release of acetylcholine (ACh) to ensure muscle contraction. During repetitive activation, ACh release diminishes, which when severe leads to transmission failure. Restoration of ACh available for release depends on two separate but interrelated processes: recycling of transmitter from the synaptic cleft, and repletion of the immediately releaseable vesicle pool from one or more reserve pools. Respiratory muscles are active continuously, so that transmitter replenishment needs to be sufficiently robust to ensure that a constant supply of ACh is available for release. The overall objective of this proposal is to further examine the role of transmitter replenishment, and the factors which regulate replenishment, in determining the integrity of transmission in respiratory neuromuscular junctions. The specific hypotheses to be tested are as follows. 1) The rapidity of, and time available for, ACh replenishment are critical determinants of transmission at the phrenic-diaphragm neuromuscular junction, especially in diseased neuromuscular junctions. 2) ACh replenishment is hastened by high frequency stimulation, an accommodation to the adverse effects of high frequency activation on release and depletion. Furthermore, the acceleration of replenishment is mediated by elevated presynaptic [Ca+ +]. 3) Hypoxia and hypothermia impair neurotransmission to a large extent by slowing transmitter replenishment, rather than primarily by a direct inhibition of transmitter release. 4) Presynaptic K+ channels regulate not only Ach release but also transmitter replenishment, providing two mechanisms of improving neurotransmission by pharmacologic manipulation of K- channel conductances. Neuromuscular transmission will be assessed using a combination of force measurements to quantify the neuromuscular component of fatigue, electrophysiological recording to determine ACh release and recovery from transmitter rundown, and optical approaches using fluorescent styry1 dyes ( FM1-43, FM2-10) to assess vesicle pool dynamics. These studies may lead to novel therapeutic approaches to respiratory muscle impairment and resulting hypercapnic respiratory failure for conditions which produce neuromuscular junction dysfunction. 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 “myasthenia gravis” (or synonyms) into the search box. This search gives you access to full-text articles. The following is a sample of items found for myasthenia gravis 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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Algaemia due to Prototheca wickerhamii in a patient with myasthenia gravis. by Mohabeer AJ, Kaplan PJ, Southern PM Jr, Gander RM.; 1997 Dec; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&rendertype=abstr act&artid=230169

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Antigen-specific modulation of experimental myasthenia gravis: Nasal tolerization with recombinant fragments of the human acetylcholine receptor [alpha]-subunit. by Barchan D, Souroujon MC, Im SH, Antozzi C, Fuchs S.; 1999 Jul 6; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=22192

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Cathepsin V is involved in the degradation of invariant chain in human thymus and is overexpressed in myasthenia gravis. by Tolosa E, Li W, Yasuda Y, Wienhold W, Denzin LK, Lautwein A, Driessen C, Schnorrer P, Weber E, Stevanovic S, Kurek R, Melms A, Bromme D.; 2003 Aug 15; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=171390

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Circulating regulatory anti --T cell receptor antibodies in patients with myasthenia gravis. by Jambou F, Zhang W, Menestrier M, Klingel-Schmitt I, Michel O, CaillatZucman S, Aissaoui A, Landemarre L, Berrih-Aknin S, Cohen-Kaminsky S.; 2003 Jul 15; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=164282

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Epitope-Specific Suppression of Antibody Response in Experimental Autoimmune Myasthenia Gravis by a Monomethoxypolyethylene Glycol Conjugate of a Myasthenogenic Synthetic Peptide. by Atassi MZ, Ruan K, Jinnai K, Oshima M, Ashizawa T.; 1992 Jul 1; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&rendertype=abstr act&artid=49395

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Immunodominant Regions for T Helper-Cell Sensitization on the Human Nicotinic Receptor [alpha] Subunit in Myasthenia Gravis. by Protti MP, Manfredi AA, Straub C, Howard JF Jr, Conti-Tronconi BM.; 1990 Oct 1; http://www.pubmedcentral.gov/picrender.fcgi?tool=pmcentrez&action=stream&blobt ype=pdf&artid=54834

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Involvement of Human Muscle Acetylcholine Receptor [alpha]-Subunit Gene (CHRNA) in Susceptibility to Myasthenia Gravis. by Garchon HJ, Djabiri F, Viard JP, Gajdos P, Bach JF.; 1994 May 24; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&rendertype=abstr act&artid=43849

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Mapping myasthenia gravis --associated T cell epitopes on human acetylcholine receptors in HLA transgenic mice. by Yang H, Goluszko E, David C, Okita DK, ContiFine B, Chan TS, Poussin MA, Christadoss P.; 2002 Apr 15; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=150946

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Markedly enhanced susceptibility to experimental autoimmune myasthenia gravis in the absence of decay-accelerating factor protection. by Lin F, Kaminski HJ, Conti-Fine BM, Wang W, Richmonds C, Medof ME.; 2002 Nov 1; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=151616

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Oral administration of a dual analog of two myasthenogenic T cell epitopes downregulates experimental autoimmune myasthenia gravis in mice. by Paas-Rozner M, Dayan M, Paas Y, Changeux JP, Wirguin I, Sela M, Mozes E.; 2000 Feb 29; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=15772

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Peptide Analogs to Pathogenic Epitopes of the Human Acetylcholine Receptor [alpha] Subunit as Potential Modulators of Myasthenia Gravis. by Zisman E, Katz-Levy Y,

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Dayan M, Kirshner SL, Paas-Rozner M, Karni A, Abramsky O, Brautbar C, Fridkin M, Sela M, Mozes E.; 1996 Apr 30; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&rendertype=abstr act&artid=39566 •

Prevention of Experimental Autoimmune Myasthenia Gravis by Manipulation of the Immune Network with a Complementary Peptide for the Acetylcholine Receptor. by Araga S, LeBoeuf RD, Blalock JE.; 1993 Sep 15; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&rendertype=abstr act&artid=47435

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Prevention of passively transferred experimental autoimmune myasthenia gravis by a phage library-derived cyclic peptide. by Venkatesh N, Im SH, Balass M, Fuchs S, Katchalski-Katzir E.; 2000 Jan 18; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=15404

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Steroids Induce Acetylcholine Receptors on Cultured Human Muscle: Implications for Myasthenia Gravis. by Kaplan I, Blakely BT, Pavlath GK, Travis M, Blau HM.; 1990 Oct 15; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&rendertype=abstr act&artid=54900

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The nature of the active suppression of responses associated with experimental autoimmune myasthenia gravis by a dual altered peptide ligand administered by different routes. by Paas-Rozner M, Sela M, Mozes E.; 2001 Oct 23; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=60107

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 myasthenia gravis, simply go to the PubMed Web site at http://www.ncbi.nlm.nih.gov/pubmed. Type “myasthenia gravis” (or synonyms) into the search box, and click “Go.” The following is the type of output you can expect from PubMed for myasthenia gravis (hyperlinks lead to article summaries): •

A case of myasthenia gravis accompanied by erythema elevatum diutinum and rheumatoid arthritis. Author(s): Wakata N, Nakazato A, Sugimoto H, Iguchi H, Saito R. Source: Journal of Neurology. 2001 May; 248(5): 435-6. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11437173&dopt=Abstract

6 PubMed was developed by the National Center for Biotechnology Information (NCBI) at the National Library of Medicine (NLM) at the National Institutes of Health (NIH). The PubMed database was developed in conjunction with publishers of biomedical literature as a search tool for accessing literature citations and linking to full-text journal articles at Web sites of participating publishers. Publishers that participate in PubMed supply NLM with their citations electronically prior to or at the time of publication.

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A new model linking intrathymic acetylcholine receptor expression and the pathogenesis of myasthenia gravis. Author(s): Levinson AI, Zheng Y, Gaulton G, Moore J, Pletcher CH, Song D, Wheatley LM. Source: Annals of the New York Academy of Sciences. 2003 September; 998: 257-65. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=14592882&dopt=Abstract

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A simple manual muscle test for myasthenia gravis: validation and comparison with the QMG score. Author(s): Sanders DB, Tucker-Lipscomb B, Massey JM. Source: Annals of the New York Academy of Sciences. 2003 September; 998: 440-4. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=14592912&dopt=Abstract

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Active management in patients with ocular manifestations of myasthenia gravis. Author(s): Bentley CR, Dawson E, Lee JP. Source: Eye (London, England). 2001 February; 15(Pt 1): 18-22. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11318287&dopt=Abstract

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Adsorption column for myasthenia gravis treatment: Medisorba MG-50. Author(s): Nakaji S, Hayashi N. Source: Therap Apher Dial. 2003 February; 7(1): 78-84. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12921120&dopt=Abstract

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Analysis of CD4+CD25+ cell population in the thymus from myasthenia gravis patients. Author(s): Balandina A, Saoudi A, Dartevelle P, Berrih-Aknin S. Source: Annals of the New York Academy of Sciences. 2003 September; 998: 275-7. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=14592885&dopt=Abstract

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Analysis of thymectomy for myasthenia gravis in older patients: a 20-year single institution experience. Author(s): Abt PL, Patel HJ, Marsh A, Schwartz SI. Source: Journal of the American College of Surgeons. 2001 April; 192(4): 459-64. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11294402&dopt=Abstract

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Anesthesia and critical care of thymectomy for myasthenia gravis. Author(s): Baraka A. Source: Chest Surg Clin N Am. 2001 May; 11(2): 337-61. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11413760&dopt=Abstract

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Anesthesia of a patient with cured myasthenia gravis. Author(s): Basaranoglu G, Erden V, Delatioglu H. Source: Anesthesia and Analgesia. 2003 June; 96(6): 1842-3; Author Reply 1843. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12761029&dopt=Abstract

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Antibodies against muscle-specific kinase in juvenile myasthenia gravis. Author(s): Anlar B, Vincent A. Source: Neuropediatrics. 2003 April; 34(2): 110-1. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12776235&dopt=Abstract

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Antibodies in myasthenia gravis and related disorders. Author(s): Vincent A, McConville J, Farrugia ME, Bowen J, Plested P, Tang T, Evoli A, Matthews I, Sims G, Dalton P, Jacobson L, Polizzi A, Blaes F, Lang B, Beeson D, Willcox N, Newsom-Davis J, Hoch W. Source: Annals of the New York Academy of Sciences. 2003 September; 998: 324-35. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=14592891&dopt=Abstract

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Antibodies in sera of patients with late-onset myasthenia gravis recognize the PEVK domain of titin. Author(s): Mihovilovic M, Ciafaloni E, Butterworth-Robinette J, Jin JP, Massey J, Sanders DB. Source: Annals of the New York Academy of Sciences. 2003 September; 998: 351-5. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=14592895&dopt=Abstract

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Anticholinergic agents for the treatment of “death rattle” in patients with myasthenia gravis. Author(s): Spiess JL, Scott SD. Source: Journal of Pain and Symptom Management. 2003 July; 26(1): 684-6. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12850651&dopt=Abstract

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Anti-cytokine autoantibodies in autoimmunity: preponderance of neutralizing autoantibodies against interferon-alpha, interferon-omega and interleukin-12 in patients with thymoma and/or myasthenia gravis. Author(s): Meager A, Wadhwa M, Dilger P, Bird C, Thorpe R, Newsom-Davis J, Willcox N. Source: Clinical and Experimental Immunology. 2003 April; 132(1): 128-36. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12653847&dopt=Abstract

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Antiphospholipid syndrome and multiple ischemic strokes in a patient with myasthenia gravis. Author(s): Kaji M, Sato Y, Kunoh H, Watanabe A, Aizawa H, Oizumi K, Abe T. Source: Kurume Med J. 2002; 49(4): 211-6. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12652972&dopt=Abstract

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Anti-titin antibodies in myasthenia gravis: tight association with thymoma and heterogeneity of nonthymoma patients. Author(s): Yamamoto AM, Gajdos P, Eymard B, Tranchant C, Warter JM, Gomez L, Bourquin C, Bach JF, Garchon HJ. Source: Archives of Neurology. 2001 June; 58(6): 885-90. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11405802&dopt=Abstract

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Assessment of esophageal function in patients with myasthenia gravis. Author(s): Linke R, Witt TN, Tatsch K. Source: Journal of Neurology. 2003 May; 250(5): 601-6. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12736742&dopt=Abstract

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Autoantibodies to IL-12 in myasthenia gravis patients with thymoma; effects on the IFN-gamma responses of healthy CD4+ T cells. Author(s): Zhang W, Liu JL, Meager A, Newsom-Davis J, Willcox N. Source: Journal of Neuroimmunology. 2003 June; 139(1-2): 102-8. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12799027&dopt=Abstract

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Autoimmunity against the ryanodine receptor in myasthenia gravis. Author(s): Skeie GO, Lunde PK, Sejersted OM, Mygland A, Aarli JA, Gilhus NE. Source: Acta Physiologica Scandinavica. 2001 March; 171(3): 379-84. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11412151&dopt=Abstract

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Autoreactive T cells to the P3A+ isoform of AChR alpha subunit in myasthenia gravis. Author(s): Suzuki S, Tanaka K, Yasuoka H, Fukuuchi Y, Kawakami Y, Kuwana M. Source: Journal of Neuroimmunology. 2003 April; 137(1-2): 177-86. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12667662&dopt=Abstract

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Beneficial effects of corticosteroids on ocular myasthenia gravis. Author(s): Kupersmith MJ, Moster M, Bhuiyan S, Warren F, Weinberg H. Source: Archives of Neurology. 1996 August; 53(8): 802-4. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=8759987&dopt=Abstract

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Benefits of early thymectomy in patients with myasthenia gravis. Author(s): Bramis J, Pikoulis E, Leppaniemi A, Felekouras E, Alexiou D, Bastounis E. Source: The European Journal of Surgery = Acta Chirurgica. 1997 December; 163(12): 897-902. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=9449441&dopt=Abstract

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Beta 2-adrenergic receptor antibodies in myasthenia gravis. Author(s): Eng H, Magnusson Y, Matell G, Lefvert AK, Saponja R, Hoebeke J. Source: Journal of Autoimmunity. 1992 April; 5(2): 213-27. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=1378277&dopt=Abstract

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beta2-adrenergic receptor gene polymorphisms in myasthenia gravis (MG). Author(s): Xu BY, Huang D, Pirskanen R, Lefvert AK. Source: Clinical and Experimental Immunology. 2000 January; 119(1): 156-60. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10606977&dopt=Abstract

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Bilateral abductor vocal fold paralysis due to myasthenia gravis. Author(s): Osei-Lah V, O'Reilly BJ, Capildeo R. Source: The Journal of Laryngology and Otology. 1999 July; 113(7): 678-9. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10605571&dopt=Abstract

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Bilateral pseudo-internuclear ophthalmoplegia in myasthenia gravis. Author(s): Ito K, Mizutani J, Murofushi T, Mizuno M. Source: Orl; Journal for Oto-Rhino-Laryngology and Its Related Specialties. 1997 MarchApril; 59(2): 122-6. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=9166884&dopt=Abstract

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Bilineage hematopoietic inhibitor and T lymphocyte dysfunction in a patient with pure red cell aplasia, myasthenia gravis and thymoma. Author(s): Murase T. Source: Experimental Hematology. 1993 March; 21(3): 451-5. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=8440342&dopt=Abstract

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Binding of peptides of the human acetylcholine receptor alpha-subunit to HLA class II of patients with myasthenia gravis. Author(s): Zisman E, Brautbar C, Sela M, Abramsky O, Battat S, Kirshner SL, Katz-Levy Y, Dayan M, Mozes E. Source: Human Immunology. 1995 November; 44(3): 121-30. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=8666548&dopt=Abstract

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Biosynthetic and synthetic AChR sequences to study T cells in myasthenia gravis. Author(s): Diethelm-Okita B, Wells G, Kuryatov A, Okita D, Howard J, Lindstrom J, Conti-Fine BM. Source: Annals of the New York Academy of Sciences. 1998 May 13; 841: 320-3. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=9668250&dopt=Abstract

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Bladder exstrophy in a neonate at risk of transient myasthenia gravis: a role for remifentanil and epidural analgesia. Author(s): Wee L, Stokes MA. Source: British Journal of Anaesthesia. 1999 May; 82(5): 774-6. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10536562&dopt=Abstract

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Blockade of CD40 ligand suppresses chronic experimental myasthenia gravis by down-regulation of Th1 differentiation and up-regulation of CTLA-4. Author(s): Im SH, Barchan D, Maiti PK, Fuchs S, Souroujon MC. Source: Journal of Immunology (Baltimore, Md. : 1950). 2001 June 1; 166(11): 6893-8. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11359850&dopt=Abstract

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Botulinum toxin for spasmodic torticollis in a patient with myasthenia gravis. Author(s): Emmerson J. Source: Movement Disorders : Official Journal of the Movement Disorder Society. 1994 May; 9(3): 367. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=8041381&dopt=Abstract

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Brain stem auditory evoked potentials reflect central nervous system involvement in myasthenia gravis. Author(s): Jech R, Ruzicka E. Source: Journal of Neurology. 1996 July; 243(7): 547-50. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=8836946&dopt=Abstract

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Breakage of tolerance to hidden cytoplasmic epitopes of the acetylcholine receptor in experimental autoimmune myasthenia gravis. Author(s): Feferman T, Im SH, Fuchs S, Souroujon MC. Source: Journal of Neuroimmunology. 2003 July; 140(1-2): 153-8. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12864983&dopt=Abstract

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Breathing disorders during sleep in myasthenia gravis. Author(s): Quera-Salva MA, Guilleminault C, Chevret S, Troche G, Fromageot C, Crowe McCann C, Stoos R, de Lattre J, Raphael JC, Gajdos P. Source: Annals of Neurology. 1992 January; 31(1): 86-92. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=1543353&dopt=Abstract

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Breathing during sleep in myasthenia gravis. Author(s): Manni R, Piccolo G, Sartori I, Castelnovo G, Raiola E, Lombardi M, Cerveri I, Fanfulla F, Tartara A. Source: Italian Journal of Neurological Sciences. 1995 December; 16(9): 589-94. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=8838784&dopt=Abstract

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Breathing pattern and central ventilatory drive in mild and moderate generalised myasthenia gravis. Author(s): Garcia Rio F, Prados C, Diez Tejedor E, Diaz Lobato S, Alvarez-Sala R, Villamor J, Pino JM. Source: Thorax. 1994 July; 49(7): 703-6. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=8066568&dopt=Abstract

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Bucillamine may induce myasthenia gravis. Author(s): Fujiyama J, Tokimura Y, Ijichi S, Arimura K, Matsuda T, Osame M. Source: Jpn J Med. 1991 January-February; 30(1): 101-2. No Abstract Available. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=1865571&dopt=Abstract

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Bulbar presentations of myasthenia gravis in the elderly patient. Author(s): Sharp HR, Degrip A, Mitchell DB, Heller A. Source: The Journal of Laryngology and Otology. 2001 January; 115(1): 1-3. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11233614&dopt=Abstract

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Castleman's disease associated with myasthenia gravis. Author(s): Day JR, Bew D, Ali M, Dina R, Smith PL. Source: The Annals of Thoracic Surgery. 2003 May; 75(5): 1648-50. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12735602&dopt=Abstract

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Cathepsin V is involved in the degradation of invariant chain in human thymus and is overexpressed in myasthenia gravis. Author(s): Tolosa E, Li W, Yasuda Y, Wienhold W, Denzin LK, Lautwein A, Driessen C, Schnorrer P, Weber E, Stevanovic S, Kurek R, Melms A, Bromme D. Source: The Journal of Clinical Investigation. 2003 August; 112(4): 517-26. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12925692&dopt=Abstract

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CD45 isoform expression in autoimmune myasthenia gravis. Author(s): Tackenberg B, Nitschke M, Willcox N, Ziegler A, Nessler S, Schumm F, Oertel WH, Hemmer B, Sommer N. Source: Autoimmunity. 2003 March; 36(2): 117-21. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12820694&dopt=Abstract

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Changes in respiratory condition after thymectomy for patients with myasthenia gravis. Author(s): Mori T, Yoshioka M, Watanabe K, Iwatani K, Kobayashi H, Terasaki H, Kawasuji M. Source: Ann Thorac Cardiovasc Surg. 2003 April; 9(2): 93-7. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12732085&dopt=Abstract

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Chiari I malformation mimicking myasthenia gravis. Author(s): Rodolico C, Girlanda P, Nicolosi C, Vita G, Bonsignore M, Tortorella G. Source: Journal of Neurology, Neurosurgery, and Psychiatry. 2003 March; 74(3): 393. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12588944&dopt=Abstract

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Childhood myasthenia gravis in an infant. Author(s): Chaudhuri Z, Pandey PK, Bhomaj S, Chauhan D, Rani LU. Source: The British Journal of Ophthalmology. 2002 June; 86(6): 704-5. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12034699&dopt=Abstract

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Childhood ocular myasthenia gravis. Author(s): Kim JH, Hwang JM, Hwang YS, Kim KJ, Chae J. Source: Ophthalmology. 2003 July; 110(7): 1458-62. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12867410&dopt=Abstract

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Childhood onset myasthenia gravis. Author(s): Raksadawan N, Kankirawatana P, Balankura K, Prateepratana P, Sangruchi T, Atchaneeyasakul LO. Source: J Med Assoc Thai. 2002 August; 85 Suppl 2: S769-77. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12403259&dopt=Abstract

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Chiropractic care of a pediatric patient with myasthenia gravis. Author(s): Alcantara J, Plaugher G, Araghi HJ. Source: Journal of Manipulative and Physiological Therapeutics. 2003 July-August; 26(6): 390-4. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12902968&dopt=Abstract

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Chronic myeloid leukaemia in a man with myasthenia gravis treated by thymectomy. Author(s): Pavithran K, Panakkel C, Roy D, Thomas M. Source: European Journal of Haematology. 2002 August; 69(2): 105-7. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12366714&dopt=Abstract

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Circulating CD4+CD25+ and CD4+CD25- T cells in myasthenia gravis. Author(s): Huang Y, Pirskanen R, Ciscombe R, Link H, Lefvert AK. Source: Annals of the New York Academy of Sciences. 2003 September; 998: 318-9. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=14592889&dopt=Abstract

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Circulating regulatory anti-T cell receptor antibodies in patients with myasthenia gravis. Author(s): Jambou F, Zhang W, Menestrier M, Klingel-Schmitt I, Michel O, CaillatZucman S, Aissaoui A, Landemarre L, Berrih-Aknin S, Cohen-Kaminsky S. Source: The Journal of Clinical Investigation. 2003 July; 112(2): 265-74. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12865414&dopt=Abstract

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Clinical case of the month. Severe progressive weakness in a 58-year-old man. Myasthenia gravis. Author(s): Sondes S, Kennedy JM, Kishner S, Lopez FA, Anthony L. Source: J La State Med Soc. 2002 November-December; 154(6): 292-5; Quiz 295. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12517024&dopt=Abstract

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Clinical correlates with anti-MuSK antibodies in generalized seronegative myasthenia gravis. Author(s): Evoli A, Tonali PA, Padua L, Monaco ML, Scuderi F, Batocchi AP, Marino M, Bartoccioni E. Source: Brain; a Journal of Neurology. 2003 October; 126(Pt 10): 2304-11. Epub 2003 June 23. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12821509&dopt=Abstract

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Clinical profile of myasthenia gravis in the Sultanate of Oman. Author(s): Jacob PC, Tharakan JT, Chand PR, Koul RL, Chacko AP. Source: Saudi Med J. 2003 July; 24(7): 774-5. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12883613&dopt=Abstract

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Clinical study of FK506 in patients with myasthenia gravis. Author(s): Konishi T, Yoshiyama Y, Takamori M, Yagi K, Mukai E, Saida T; Japanese FK506 MG Study Group. Source: Muscle & Nerve. 2003 November; 28(5): 570-4. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=14571458&dopt=Abstract

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Clinical, electrophysiological and immunological remissions after thymectomy in myasthenia gravis. Author(s): Kostera-Pruszczyk A, Emeryk-Szajewska B, Switalska J, StrugalskaCynowska H, Rowinska-Marcinska K, Nowak-Michalska T, Szyluk B. Source: Clinical Neurophysiology : Official Journal of the International Federation of Clinical Neurophysiology. 2002 April; 113(4): 615-9. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11956007&dopt=Abstract

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Colon carcinoma after thymectomy for myasthenia gravis: report of a case. Author(s): Tanakaya K, Konaga E, Takeuchi H, Yasui Y, Takeda A, Yunoki Y, Murakami I. Source: Surgery Today. 2002; 32(10): 896-8. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12376788&dopt=Abstract

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Controlled study of EMG activity of the jaw closers and openers during mastication in patients with myasthenia gravis. Author(s): van der Bilt A, Weijnen FG, Bosman F, van der Glas HW, Kuks JB. Source: European Journal of Oral Sciences. 2001 June; 109(3): 160-4. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11456345&dopt=Abstract

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CT-guided percutaneous ethanol injection of the thymus for treatment of myasthenia gravis. Author(s): Wang P, Zuo C, Tian J, Qian Z, Ren F, Shao C, Wang M, Lu T. Source: Ajr. American Journal of Roentgenology. 2003 September; 181(3): 721-4. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12933467&dopt=Abstract

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Decade-long experience with surgical therapy of myasthenia gravis: early complications of 324 transsternal thymectomies. Author(s): Kas J, Kiss D, Simon V, Svastics E, Major L, Szobor A. Source: The Annals of Thoracic Surgery. 2001 November; 72(5): 1691-7. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11722066&dopt=Abstract

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Decreased expression of c-myc family genes in thymuses from myasthenia gravis patients. Author(s): Nagata T, Onodera H, Ohuchi M, Suzuki Y, Tago H, Fujihara K, Ishii N, Sugamura K, Shoji Y, Handa M, Tabayashi K, Itoyama Y. Source: Journal of Neuroimmunology. 2001 April 2; 115(1-2): 199-202. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11282171&dopt=Abstract

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Decremental response of the nasalis and hypothenar muscles in myasthenia gravis. Author(s): Niks EH, Badrising UA, Verschuuren JJ, Van Dijk JG. Source: Muscle & Nerve. 2003 August; 28(2): 236-8. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12872330&dopt=Abstract

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Dendritic cells exposed in vitro to TGF-beta1 ameliorate experimental autoimmune myasthenia gravis. Author(s): Yarilin D, Duan R, Huang YM, Xiao BG. Source: Clinical and Experimental Immunology. 2002 February; 127(2): 214-9. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11876742&dopt=Abstract

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Dendritic cells in hyperplastic thymuses from patients with myasthenia gravis. Author(s): Nagane Y, Utsugisawa K, Obara D, Yamagata M, Tohgi H. Source: Muscle & Nerve. 2003 May; 27(5): 582-9. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12707978&dopt=Abstract

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Detection and morphology of thymic remnants after video-assisted thoracoscopic extended thymectomy (VATET) in patients with myasthenia gravis. Author(s): Scelsi R, Ferro MT, Scelsi L, Novellino L, Mantegazza R, Cornelio F, Porta M, Longoni C, Pezzuoli G. Source: Int Surg. 1996 January-March; 81(1): 14-7. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=8803698&dopt=Abstract

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Detection of HTLV-I tax-rex and pol gene sequences of thymus gland in a large group of patients with myasthenia gravis. Author(s): Manca N, Perandin F, De Simone N, Giannini F, Bonifati D, Angelini C. Source: Journal of Acquired Immune Deficiency Syndromes (1999). 2002 March 1; 29(3): 300-6. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11873081&dopt=Abstract

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Development of a thymectomy trial in nonthymomatous myasthenia gravis patients receiving immunosuppressive therapy. Author(s): Wolfe GI, Kaminski HJ, Jaretzki A 3rd, Swan A, Newsom-Davis J. Source: Annals of the New York Academy of Sciences. 2003 September; 998: 473-80. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=14592916&dopt=Abstract

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Development of generalized disease at 2 years in patients with ocular myasthenia gravis. Author(s): Kupersmith MJ, Latkany R, Homel P. Source: Archives of Neurology. 2003 February; 60(2): 243-8. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12580710&dopt=Abstract

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Development of generalized myasthenia gravis in patients with ocular myasthenia gravis. Author(s): Papapetropoulos TH, Ellul J, Tsibri E. Source: Archives of Neurology. 2003 October; 60(10): 1491-2. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=14568823&dopt=Abstract

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Development of myasthenia gravis during treatment of chronic hepatitis C with interferon-alpha and ribavirin. Author(s): Weegink CJ, Chamuleau RA, Reesink HW, Molenaar DS. Source: Journal of Gastroenterology. 2001 October; 36(10): 723-4. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11686485&dopt=Abstract

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Development of myasthenia gravis in a patient with multiple sclerosis during treatment with glatiramer acetate. Author(s): Frese A, Bethke F, Ludemann P, Stogbauer F. Source: Journal of Neurology. 2000 September; 247(9): 713. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11081814&dopt=Abstract

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Did this patient actually have myasthenia gravis (MG)? Author(s): Cooper J, Pollak GJ, Ciuffreda KJ, Kruger P, Feldman J. Source: Journal of Neuro-Ophthalmology : the Official Journal of the North American Neuro-Ophthalmology Society. 2000 December; 20(4): 291-2. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11130761&dopt=Abstract

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Difference in distribution of muscle weakness between myasthenia gravis and the Lambert-Eaton myasthenic syndrome. Author(s): Wirtz PW, Sotodeh M, Nijnuis M, Van Doorn PA, Van Engelen BG, Hintzen RQ, De Kort PL, Kuks JB, Twijnstra A, De Visser M, Visser LH, Wokke JH, Wintzen AR, Verschuuren JJ. Source: Journal of Neurology, Neurosurgery, and Psychiatry. 2002 December; 73(6): 7668. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12438488&dopt=Abstract

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Difference in sensitivity to vecuronium between patients with ocular and generalized myasthenia gravis. Author(s): Itoh H, Shibata K, Nitta S. Source: British Journal of Anaesthesia. 2001 December; 87(6): 885-9. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11878691&dopt=Abstract

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Differences between the epsilon and gamma subunits of the acetylcholine receptor (AChR) may be significant in autoimmune myasthenia gravis. Author(s): Ragheb S, Lisak RP. Source: Annals of the New York Academy of Sciences. 2003 September; 998: 336-8. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=14592892&dopt=Abstract

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Different age-related effects of thymectomy in myasthenia gravis: role of thymoma, zinc, thymulin, IL-2 and IL-6. Author(s): Mocchegiani E, Giacconi R, Muzzioli M, Gasparini N, Provinciali L, Spazzafumo L, Licastro F. Source: Mechanisms of Ageing and Development. 2000 August 15; 117(1-3): 79-91. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10958925&dopt=Abstract

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Diseases associated with myasthenia gravis. Author(s): Girija AS. Source: J Assoc Physicians India. 1999 March; 47(3): 354. No Abstract Available. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10999146&dopt=Abstract

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Distal myasthenia gravis frequency and clinical course in a large prospective series. Author(s): Werner P, Kiechl S, Loscher W, Poewe W, Willeit J. Source: Acta Neurologica Scandinavica. 2003 September; 108(3): 209-11. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12911465&dopt=Abstract

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Dominantly inherited familial myasthenia gravis as a separate genetic entity without involvement of defined candidate gene loci. Author(s): Li F, Szobor A, Croxen R, Anselmo V, Yuan QP, Lindblad K, Schalling M, Komoly S, Beeson D, Larsson C. Source: International Journal of Molecular Medicine. 2001 March; 7(3): 289-94. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11179509&dopt=Abstract

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Effect of patient-controlled epidural analgesia for pain relief after thymectomy in patients with myasthenia gravis. Author(s): Lu JC, Lin CS, Liang SW, Xiao JF, Gu MN. Source: Di Yi June Yi Da Xue Xue Bao. 2002 May; 22(5): 453-5. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12390715&dopt=Abstract

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Effect of thymectomy on human peripheral blood T cell pools in myasthenia gravis. Author(s): Sempowski G, Thomasch J, Gooding M, Hale L, Edwards L, Ciafaloni E, Sanders D, Massey J, Douek D, Koup R, Haynes B. Source: Journal of Immunology (Baltimore, Md. : 1950). 2001 February 15; 166(4): 280817. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11160348&dopt=Abstract

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Effects of FK506 on myasthenia gravis patients with high interleukin-2 productivity in peripheral blood mononuclear cells. Author(s): Utsugisawa K, Nagane Y, Yonezawa H, Obara D, Kondoh R, Tohgi H. Source: Muscle & Nerve. 2003 February; 27(2): 245-8. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12548534&dopt=Abstract

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Effects of myasthenia gravis patients' sera with different autoantibodies on slow K+ current at mouse motor nerve terminals. Author(s): Xu TH, Ding J, Shi YL, Li MF, Lu CZ, Qiao J. Source: Neurological Research. 2003 January; 25(1): 58-62. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12564127&dopt=Abstract

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Effects of resistance exercise and creatine supplementation on myasthenia gravis: a case study. Author(s): Stout JR, Eckerson JM, May E, Coulter C, Bradley-Popovich GE. Source: Medicine and Science in Sports and Exercise. 2001 June; 33(6): 869-72. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11404649&dopt=Abstract

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Enhancement of noradrenergic neural transmission: an effective therapy of myasthenia gravis: a report on 52 consecutive patients. Author(s): Lechin F, van der Dijs B, Pardey-Maldonado B, John E, Jimenez V, Orozco B, Baez S, Lechin ME. Source: J Med. 2000; 31(5-6): 333-61. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11508327&dopt=Abstract

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Epidemiology of myasthenia gravis: a population-based study in Stockholm, Sweden. Author(s): Kalb B, Matell G, Pirskanen R, Lambe M. Source: Neuroepidemiology. 2002 September-October; 21(5): 221-5. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12207149&dopt=Abstract

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Epidemiology of seropositive myasthenia gravis in Greece. Author(s): Poulas K, Tsibri E, Kokla A, Papanastasiou D, Tsouloufis T, Marinou M, Tsantili P, Papapetropoulos T, Tzartos SJ. Source: Journal of Neurology, Neurosurgery, and Psychiatry. 2001 September; 71(3): 352-6. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11511710&dopt=Abstract

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Etiology, mechanisms, and anesthesia implications of autoimmune myasthenia gravis. Author(s): Ceremuga TE, Yao XL, McCabe JT. Source: Aana Journal. 2002 August; 70(4): 301-10. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12242929&dopt=Abstract

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Evidence for a central cholinergic deficit in myasthenia gravis. Author(s): Fotiou F, Fountoulakis KN. Source: The Journal of Neuropsychiatry and Clinical Neurosciences. 2000 Fall; 12(4): 514-5. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11083171&dopt=Abstract

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Evidence for distinct mechanisms in the shaping of the CD4 T cell repertoire in histologically distinct myasthenia gravis-associated thymomas. Author(s): Strobel P, Helmreich M, Kalbacher H, Muller-Hermelink HK, Marx A. Source: Developmental Immunology. 2001; 8(3-4): 279-90. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11785677&dopt=Abstract

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Evidence of underdiagnosis of myasthenia gravis in older people. Author(s): Vincent A, Clover L, Buckley C, Grimley Evans J, Rothwell PM; UK Myasthenia Gravis Survey. Source: Journal of Neurology, Neurosurgery, and Psychiatry. 2003 August; 74(8): 1105-8. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12876244&dopt=Abstract

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Exacerbation of myasthenia gravis associated with cocaine use. Author(s): Daras M, Samkoff LM, Koppel BS. Source: Neurology. 1996 January; 46(1): 271-2. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=8559400&dopt=Abstract

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Experimental autoimmune myasthenia gravis in mice expressing human immunoglobulin loci. Author(s): Stassen MH, Meng F, Melgert E, Machiels BM, Im SH, Fuchs S, Gerritsen AF, van Dijk MA, van de Winkel JG, De Baets MH. Source: Journal of Neuroimmunology. 2003 February; 135(1-2): 56-61. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12576224&dopt=Abstract

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Expression of ciliary neurotrophic factor receptor in myasthenia gravis. Author(s): Poea S, Guyon T, Levasseur P, Berrih-Aknin S. Source: Journal of Neuroimmunology. 2001 November 1; 120(1-2): 180-9. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11694333&dopt=Abstract

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Expression of transforming growth factor-beta1 in thymus of myasthenia gravis patients: correlation with pathological abnormalities. Author(s): Bernasconi P, Passerini L, Annoni A, Ubiali F, Marcozzi C, Confalonieri P, Cornelio F, Mantegazza R. Source: Annals of the New York Academy of Sciences. 2003 September; 998: 278-83. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=14592886&dopt=Abstract

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Extended thymectomy in myasthenia gravis: a team-work of neurologist, thoracic surgeon and anaesthesist may improve the outcome. Author(s): Mussi A, Lucchi M, Murri L, Ricciardi R, Luchini L, Angeletti CA. Source: European Journal of Cardio-Thoracic Surgery : Official Journal of the European Association for Cardio-Thoracic Surgery. 2001 May; 19(5): 570-5. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11343933&dopt=Abstract

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Extended trans-sternal thymectomy for myasthenia gravis. Author(s): Masaoka A. Source: Chest Surg Clin N Am. 2001 May; 11(2): 369-87. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11413762&dopt=Abstract

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Extramedullary plasmacytoma presenting with myasthenia gravis and mediastinal mass. Author(s): Ahmed AR, Marchbank AJ, Nicholson AG, Wotherspoon AC, Ladas GP. Source: The Annals of Thoracic Surgery. 2000 October; 70(4): 1390-2. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11081905&dopt=Abstract

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Extraocular muscle responses to orbital cooling (ice test) for ocular myasthenia gravis diagnosis. Author(s): Ellis FD, Hoyt CS, Ellis FJ, Jeffery AR, Sondhi N. Source: J Aapos. 2000 October; 4(5): 271-81. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11040476&dopt=Abstract

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Facioscapulohumeral muscular dystrophy and myasthenia gravis co-existing in the same patient: a case report. Author(s): McGonigal A, Thomas AM, Petty RK. Source: Journal of Neurology. 2002 February; 249(2): 219-20. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11985390&dopt=Abstract

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Factors influencing improvement and remission rates after thymectomy for myasthenia gravis. Author(s): de Perrot M, Licker M, Spiliopoulos A. Source: Respiration; International Review of Thoracic Diseases. 2001; 68(6): 601-5. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11786715&dopt=Abstract

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Factors related to long-term effects of thymectomy on myasthenia gravis. Author(s): Jiang Y, Fan S, Chen J, Wang R, Chen W. Source: Chinese Medical Journal. 1995 March; 108(3): 199-203. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=7796628&dopt=Abstract

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Factors that determine the severity of experimental myasthenia gravis. Author(s): Drachman DB, McIntosh KR, Yang B. Source: Annals of the New York Academy of Sciences. 1998 May 13; 841: 262-82. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=9668247&dopt=Abstract

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Myasthenia Gravis

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Failure of intravenously administered immunoglobulin in the treatment of neonatal myasthenia gravis. Author(s): Tagher RJ, Baumann R, Desai N. Source: The Journal of Pediatrics. 1999 February; 134(2): 233-5. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=9931536&dopt=Abstract

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Failure to down-regulate Bcl-2 protein in thymic germinal center B cells in myasthenia gravis. Author(s): Shiono H, Fujii Y, Okumura M, Takeuchi Y, Inoue M, Matsuda H. Source: European Journal of Immunology. 1997 April; 27(4): 805-9. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=9130628&dopt=Abstract

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Familial autoimmune myasthenia gravis. Author(s): Tan JH, Ho KH. Source: Singapore Med J. 2001 April; 42(4): 178-9. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11465320&dopt=Abstract

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Familial autoimmune myasthenia gravis: report of four families. Author(s): Evoli A, Batocchi AP, Zelano G, Uncini A, Palmisani MT, Tonali P. Source: Journal of Neurology, Neurosurgery, and Psychiatry. 1995 June; 58(6): 729-31. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=7608676&dopt=Abstract

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Fatigue and its impact on patients with myasthenia gravis. Author(s): Paul RH, Cohen RA, Goldstein JM, Gilchrist JM. Source: Muscle & Nerve. 2000 September; 23(9): 1402-6. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10951443&dopt=Abstract

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Fatigue in Myasthenia Gravis patients. Author(s): Kittiwatanapaisan W, Gauthier DK, Williams AM, Oh SJ. Source: The Journal of Neuroscience Nursing : Journal of the American Association of Neuroscience Nurses. 2003 April; 35(2): 87-93, 106. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12795035&dopt=Abstract

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FcgammaRIIA and FcgammaRIIIB polymorphisms in myasthenia gravis. Author(s): Raknes G, Skeie GO, Gilhus NE, Aadland S, Vedeler C. Source: Journal of Neuroimmunology. 1998 January; 81(1-2): 173-6. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=9521619&dopt=Abstract

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FK506 prevents induction of rat experimental autoimmune myasthenia gravis. Author(s): Yoshikawa H, Iwasa K, Satoh K, Takamori M. Source: Journal of Autoimmunity. 1997 February; 10(1): 11-6. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=9080295&dopt=Abstract

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Fluoxetine treatment for weight reduction in steroid-induced obesity: a pilot study in myasthenia gravis patients. Author(s): Achiron A, Barak Y, Noy S, Pinhas-Hamiel O. Source: European Neuropsychopharmacology : the Journal of the European College of Neuropsychopharmacology. 1999 January; 9(1-2): 111-3. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10082236&dopt=Abstract

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Focus on cosmesis in thymectomy for myasthenia gravis. Author(s): Granone P, Margaritora S, Cesario A, Galetta D. Source: The Annals of Thoracic Surgery. 2001 October; 72(4): 1441-2. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11603495&dopt=Abstract

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Foreign body aspiration: a presenting sign of juvenile myasthenia gravis. Author(s): Murray DJ, McAllister J. Source: Anesthesiology. 2001 August; 95(2): 555-7. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11506135&dopt=Abstract

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Foreign body aspiration: an unusual presentation of myasthenia gravis. Author(s): Patel U, Forsen J. Source: Otolaryngology and Head and Neck Surgery. 2001 June; 124(6): 698-9. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11391268&dopt=Abstract

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Frequency and clinical correlates of vitiligo in myasthenia gravis. Author(s): Kubota A, Komiyama A, Tanigawa A, Hasegawa O. Source: Journal of Neurology. 1997 June; 244(6): 388-9. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=9249625&dopt=Abstract

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Fulminant myasthenia gravis manifested after removal of anterior mediastinal tumor. Author(s): Onoda K, Namikawa S, Takao M, Shimpo H, Miura S, Narita Y, Kuzuhara S, Yada I. Source: The Annals of Thoracic Surgery. 1996 November; 62(5): 1534-6. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=8893607&dopt=Abstract

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Functional expression of receptors for calcitonin gene-related peptide, calcitonin, and vasoactive intestinal peptide in the human thymus and thymomas from myasthenia gravis patients. Author(s): Marie J, Wakkach A, Coudray A, Chastre E, Berrih-Aknin S, Gespach C. Source: Journal of Immunology (Baltimore, Md. : 1950). 1999 February 15; 162(4): 210312. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=9973484&dopt=Abstract

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Myasthenia Gravis

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Future therapeutic strategies in autoimmune myasthenia gravis. Author(s): Psaridi-Linardaki L, Mamalaki A, Tzartos SJ. Source: Annals of the New York Academy of Sciences. 2003 September; 998: 539-48. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=14592926&dopt=Abstract

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Gabapentin may be hazardous in myasthenia gravis. Author(s): Boneva N, Brenner T, Argov Z. Source: Muscle & Nerve. 2000 August; 23(8): 1204-8. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10918256&dopt=Abstract

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Galectin-1 is expressed by thymic epithelial cells in myasthenia gravis. Author(s): Hafer-Macko C, Pang M, Seilhamer JJ, Baum LG. Source: Glycoconjugate Journal. 1996 August; 13(4): 591-7. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=8872116&dopt=Abstract

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Gender prevalence in childhood multiple sclerosis and myasthenia gravis. Author(s): Haliloglu G, Anlar B, Aysun S, Topcu M, Topaloglu H, Turanli G, Yalnizoglu D. Source: Journal of Child Neurology. 2002 May; 17(5): 390-2. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12150589&dopt=Abstract

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Generalized myasthenia gravis following use of D-pencillamine in Wilson's disease. Author(s): Narayanan CS, Behari M. Source: J Assoc Physicians India. 1999 June; 47(6): 648. No Abstract Available. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10999174&dopt=Abstract

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Genetic association of Ctla-4 to myasthenia gravis with thymoma. Author(s): Huang D, Liu L, Noren K, Xia SQ, Trifunovic J, Pirskanen R, Lefvert AK. Source: Journal of Neuroimmunology. 1998 August 1; 88(1-2): 192-8. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=9688341&dopt=Abstract

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Genetics of childhood disorders: XXX. Autoimmune disorders, part 3: myasthenia gravis and Rasmussen's encephalitis. Author(s): Lombroso PJ, Mercadante MT. Source: Journal of the American Academy of Child and Adolescent Psychiatry. 2001 September; 40(9): 1115-7. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11556637&dopt=Abstract

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Genomic organization and lack of transcription of the nicotinic acetylcholine receptor subunit genes in myasthenia gravis-associated thymoma. Author(s): Geuder KI, Marx A, Witzemann V, Schalke B, Kirchner T, Muller-Hermelink HK. Source: Laboratory Investigation; a Journal of Technical Methods and Pathology. 1992 April; 66(4): 452-8. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=1583885&dopt=Abstract

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Geographic opinions on speech impairment in myasthenia gravis. Author(s): D'Alessandro R. Source: Archives of Neurology. 1992 April; 49(4): 346. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=1558506&dopt=Abstract

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Giant thymolipoma in association with myasthenia gravis. Author(s): Cekirdekci A, Akpolat N, Ayan E, Duran M. Source: European Journal of Cardio-Thoracic Surgery : Official Journal of the European Association for Cardio-Thoracic Surgery. 2003 March; 23(3): 422. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12614818&dopt=Abstract

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Glomerulonephritis associated with myasthenia gravis. Author(s): Valli G, Fogazzi GB, Cappellari A, Rivolta E. Source: American Journal of Kidney Diseases : the Official Journal of the National Kidney Foundation. 1998 February; 31(2): 350-5. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=9469510&dopt=Abstract

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Glucocorticoid therapy for myasthenia gravis resulting in resorption of the mandibular condyles. Author(s): Cowan J, Moenning JE, Bussard DA. Source: Journal of Oral and Maxillofacial Surgery : Official Journal of the American Association of Oral and Maxillofacial Surgeons. 1995 September; 53(9): 1091-6. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=7643281&dopt=Abstract

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Grades of exophthalmos and thyrotropin-binding inhibitory immunoglobulin in patients with myasthenia gravis. Author(s): Okada S, Saito E, Ogawa T, Sadamoto K, Kinoshita M. Source: European Neurology. 1995; 35(2): 99-103. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=7796844&dopt=Abstract

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Graves' disease associated with myasthenia gravis: report of one case. Author(s): Chu HY, Shu SG, Mak SC, Chi CS. Source: Zhonghua Min Guo Xiao Er Ke Yi Xue Hui Za Zhi. 1992 November-December; 33(6): 457-61. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=1306932&dopt=Abstract

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Myasthenia Gravis

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Graves' disease: associated ocular myasthenia gravis and a thymic cyst. Author(s): Peacey SR, Belchetz PE. Source: Journal of the Royal Society of Medicine. 1993 May; 86(5): 297-8. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=8505758&dopt=Abstract

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Gravin, an autoantigen recognized by serum from myasthenia gravis patients, is a kinase scaffold protein. Author(s): Nauert JB, Klauck TM, Langeberg LK, Scott JD. Source: Current Biology : Cb. 1997 January 1; 7(1): 52-62. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=9000000&dopt=Abstract

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Health-related quality of life in patients with myasthenia gravis and the relationship between patient-oriented assessment and conventional measurements. Author(s): Padua L, Evoli A, Aprile I, Caliandro P, Mazza S, Padua R, Tonali P. Source: Neurological Sciences : Official Journal of the Italian Neurological Society and of the Italian Society of Clinical Neurophysiology. 2001 October; 22(5): 363-9. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11917973&dopt=Abstract

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Heterogeneity and immunotherapy of specific T-cells in myasthenia gravis. Author(s): Bond A, Corlett L, Nagvekar N, Jacobson L, Pantic N, Beeson D, Nicolle M, Vincent A, Newsom-Davis J, Spack E, Willcox N. Source: Biochemical Society Transactions. 1997 May; 25(2): 665-70. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=9191178&dopt=Abstract

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Heterogeneous immunogenetic background in Japanese adults with myasthenia gravis. Author(s): Suzuki S, Kuwana M, Yasuoka H, Tanaka K, Fukuuchi Y, Kawakami Y. Source: Journal of the Neurological Sciences. 2001 August 15; 189(1-2): 59-64. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11535234&dopt=Abstract

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High-dose immunosuppressive therapy in generalised myasthenia gravis--a 2-year follow-up study. Author(s): Heckmann JM, LeePan EB, Eastman RW. Source: South African Medical Journal. Suid-Afrikaanse Tydskrif Vir Geneeskunde. 2001 September; 91(9): 765-70. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11680327&dopt=Abstract

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High-dose intravenous immunoglobulin G treatment of myasthenia gravis. Author(s): Ferrero B, Durelli L. Source: Neurological Sciences : Official Journal of the Italian Neurological Society and of the Italian Society of Clinical Neurophysiology. 2002 April; 23 Suppl 1: S9-24. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12032583&dopt=Abstract

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High-dose intravenous immunoglobulin in transient neonatal myasthenia gravis. Author(s): Bassan H, Muhlbaur B, Tomer A, Spirer Z. Source: Pediatric Neurology. 1998 February; 18(2): 181-3. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=9535308&dopt=Abstract

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High-dose intravenous immunoglobulin therapy for myasthenia gravis. Author(s): Jongen JL, van Doorn PA, van der Meche FG. Source: Journal of Neurology. 1998 January; 245(1): 26-31. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=9457625&dopt=Abstract

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High-dose intravenous immunoglobulin therapy in juvenile myasthenia gravis. Author(s): Selcen D, Dabrowski ER, Michon AM, Nigro MA. Source: Pediatric Neurology. 2000 January; 22(1): 40-3. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10669204&dopt=Abstract

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Highly purified oligo-His tagged human recombinant alpha(1)-AChR is immunogenic in vivo and suitable for T cell stimulation in vitro in experimental and human myasthenia gravis. Author(s): Voltz R, Kamm C, Padberg F, Malotka J, Kerschensteiner M, Spuler S, Tzartos S, Dornmair K. Source: Journal of Neuroimmunology. 1997 December; 80(1-2): 131-6. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=9413268&dopt=Abstract

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High-temperature repetitive nerve stimulation in myasthenia gravis. Author(s): Rutkove SB, Shefner JM, Wang AK, Ronthal M, Raynor EM. Source: Muscle & Nerve. 1998 November; 21(11): 1414-8. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=9771664&dopt=Abstract

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HLA-DQ associations and T-cell receptor V-gene usage in peripheral blood of Swedish myasthenia gravis patients. Author(s): Hjelmstrom P, Giscombe R, Lefvert AK, Grunewald J, Pirskanen R, Sanjeevi CB. Source: European Journal of Immunogenetics : Official Journal of the British Society for Histocompatibility and Immunogenetics. 1997 June; 24(3): 179-89. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=9226124&dopt=Abstract

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HLA-DQ6 transgenic mice resistance to experimental autoimmune myasthenia gravis is linked to reduced acetylcholine receptor-specific IFN-gamma, IL-2 and IL-10 production. Author(s): Poussin MA, Goluszko E, David CS, Franco JU, Christadoss P. Source: Journal of Autoimmunity. 2001 November; 17(3): 175-80. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11712854&dopt=Abstract

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Homology between Fas and nicotinic acetylcholine receptor protein in a thymoma with myasthenia gravis--immunohistochemical and biochemical study. Author(s): Kawanami S, Mori S, Ueda H. Source: Fukuoka Igaku Zasshi. 2000 May; 91(5): 123-31. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10916854&dopt=Abstract

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How to recognise myasthenia gravis. Author(s): Freedman S. Source: The Practitioner. 1996 December; 240(1569): 686, 689-91. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=8995889&dopt=Abstract

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Human anti-nicotinic acetylcholine receptor recombinant Fab fragments isolated from thymus-derived phage display libraries from myasthenia gravis patients reflect predominant specificities in serum and block the action of pathogenic serum antibodies. Author(s): Graus YF, de Baets MH, Parren PW, Berrih-Aknin S, Wokke J, van Breda Vriesman PJ, Burton DR. Source: Journal of Immunology (Baltimore, Md. : 1950). 1997 February 15; 158(4): 191929. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=9029134&dopt=Abstract

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Human foamy virus genome in the thymus of myasthenia gravis patients. Author(s): Liu WT, Kao KP, Liu YC, Chang KS. Source: Zhonghua Min Guo Wei Sheng Wu Ji Mian Yi Xue Za Zhi. 1996 August; 29(3): 162-5. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10592798&dopt=Abstract

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Human IgG monoclonal autoantibodies against muscle acetylcholine receptor: direct evidence for clonal heterogeneity of the antiself humoral response in myasthenia gravis. Author(s): Cardona A, Garchon HJ, Vernet-der-Garabedian B, Morel E, Gajdos P, Bach JF. Source: Journal of Neuroimmunology. 1994 August; 53(1): 9-16. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=8051300&dopt=Abstract

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Human muscle acetylcholine receptor alpha-subunit gene (CHRNA1) association with autoimmune myasthenia gravis in black, mixed-ancestry and Caucasian subjects. Author(s): Heckmann JM, Morrison KE, Emeryk-Szajewska B, Strugalska H, Bergoffen J, Willcox N, Newsom-Davis J. Source: Journal of Autoimmunity. 1996 April; 9(2): 175-80. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=8738961&dopt=Abstract

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Humoral response to the human heat shock 60 kDa protein in myasthenia gravis. Author(s): Astarloa R, Martinez Castrillo JC. Source: Journal of the Neurological Sciences. 1996 February; 135(2): 182-3. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=8867078&dopt=Abstract

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Hypereosinophilic syndrome with generalized myasthenia gravis. Author(s): Ishida Y, Hayashi M, Higaki A, Matsumoto K, Iikura Y, Ishikawa J, Kida K. Source: The Journal of Pediatrics. 1996 March; 128(3): 369-72. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=8774507&dopt=Abstract

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Ice pack test for myasthenia gravis. A simple, noninvasive and safe diagnostic method. Author(s): Czaplinski A, Steck AJ, Fuhr P. Source: Journal of Neurology. 2003 July; 250(7): 883-4. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12883938&dopt=Abstract

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Ice test for ocular myasthenia gravis. Author(s): Lertchavanakul A, Gamnerdsiri P, Hirunwiwatkul P. Source: J Med Assoc Thai. 2001 June; 84 Suppl 1: S131-6. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11529325&dopt=Abstract

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Identification of disease-specific autoantibodies in seronegative myasthenia gravis. Author(s): Bartoccioni E, Marino M, Evoli A, Ruegg MA, Scuderi F, Provenzano C. Source: Annals of the New York Academy of Sciences. 2003 September; 998: 356-8. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=14592896&dopt=Abstract

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IL-1 genes in myasthenia gravis: IL-1A -889 polymorphism associated with sex and age of disease onset. Author(s): Sciacca FL, Ferri C, Veglia F, Andreetta F, Mantegazza R, Cornelio F, Franciotta D, Piccolo G, Cosi V, Batocchi AP, Evoli A, Grimaldi LM. Source: Journal of Neuroimmunology. 2002 January; 122(1-2): 94-9. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11777547&dopt=Abstract

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Immunoadsorption in myasthenia gravis based on specific ligands mimicking the immunogenic sites of the acetylcholine receptor. Author(s): Takamori M, Maruta T. Source: Therapeutic Apheresis : Official Journal of the International Society for Apheresis and the Japanese Society for Apheresis. 2001 October; 5(5): 340-50. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11778918&dopt=Abstract

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Immunoglobulin treatment versus plasma exchange in patients with chronic moderate to severe myasthenia gravis. Author(s): Ronager J, Ravnborg M, Hermansen I, Vorstrup S. Source: Artificial Organs. 2001 December; 25(12): 967-73. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11843764&dopt=Abstract

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In myasthenia gravis, clinical and immunological improvement post-thymectomy segregate with results of in vitro antibody secretion by immunocytes. Author(s): Katzberg HD, Aziz T, Oger J. Source: Journal of the Neurological Sciences. 2002 October 15; 202(1-2): 77-83. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12220697&dopt=Abstract

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Incidence and characteristics of Myasthenia gravis in Dar Es Salaam, Tanzania. Author(s): Matuja WB, Aris EA, Gabone J, Mgaya EM. Source: East Afr Med J. 2001 September; 78(9): 473-6. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11921580&dopt=Abstract

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Increased serum levels of the interferon-gamma-inducing cytokine interleukin-18 in myasthenia gravis. Author(s): Jander S, Stoll G. Source: Neurology. 2002 July 23; 59(2): 287-9. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12136075&dopt=Abstract

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Indolent T-lymphoblastic proliferation: report of a case with an 11-year history and association with myasthenia gravis. Author(s): Strauchen JA. Source: The American Journal of Surgical Pathology. 2001 March; 25(3): 411-5. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11224614&dopt=Abstract

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Induction of myasthenia gravis in HLA transgenic mice by immunization with human acetylcholine receptors. Author(s): Yang H, Goluszko E, David C, Okita DK, Conti-Fine B, Chan TS, Poussin MA, Christadoss P. Source: Annals of the New York Academy of Sciences. 2003 September; 998: 375-8. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=14592899&dopt=Abstract

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Induction of myasthenia gravis, myositis, and insulin-dependent diabetes mellitus by high-dose interleukin-2 in a patient with renal cell cancer. Author(s): Fraenkel PG, Rutkove SB, Matheson JK, Fowkes M, Cannon ME, Patti ME, Atkins MB, Gollob JA. Source: Journal of Immunotherapy (Hagerstown, Md. : 1997). 2002 July-August; 25(4): 373-8. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12142560&dopt=Abstract

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Infrasternal mediastinoscopic thymectomy in myasthenia gravis: surgical results in 23 patients. Author(s): Uchiyama A, Shimizu S, Murai H, Kuroki S, Okido M, Tanaka M. Source: The Annals of Thoracic Surgery. 2001 December; 72(6): 1902-5. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11789768&dopt=Abstract

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Injury to the phrenic and recurrent nerves needs to be avoided in the performance of thymectomy for myasthenia gravis. Author(s): Jaretzki A 3rd. Source: The Annals of Thoracic Surgery. 2002 August; 74(2): 633; Author Reply 634. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12173873&dopt=Abstract

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Interleukin-2 production by peripheral blood mononuclear cells from patients with myasthenia gravis. Author(s): Utsugisawa K, Nagane Y, Obara D, Kondoh R, Yonezawa H, Tohgi H. Source: European Neurology. 2003; 49(3): 160-3. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12646760&dopt=Abstract

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Interleukin-2 Pseudomonas exotoxin chimeric protein is cytotoxic to B cell cultures derived from myasthenia gravis patients. Author(s): Steinberger I, Brenner T, Lorberboum-Galski H. Source: Journal of the Neurological Sciences. 1995 November; 133(1-2): 183-91. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=8583224&dopt=Abstract

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Intravenous immunoglobulin for myasthenia gravis. Author(s): Gajdos P, Chevret S, Toyka K. Source: Cochrane Database Syst Rev. 2003; (2): Cd002277. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12804431&dopt=Abstract

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Intravenous immunoglobulin in the preparation of thymectomy for myasthenia gravis. Author(s): Huang CS, Hsu HS, Kao KP, Huang MH, Huang BS. Source: Acta Neurologica Scandinavica. 2003 August; 108(2): 136-8. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12859292&dopt=Abstract

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Intravenous immunoglobulin monotherapy in long-term treatment of myasthenia gravis. Author(s): Wegner B, Ahmed I. Source: Clinical Neurology and Neurosurgery. 2002 December; 105(1): 3-8. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12445915&dopt=Abstract

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Isolated distal hand weakness as the only presenting symptom of myasthenia gravis. Author(s): Karacostas D, Mavromatis I, Georgakoudas G, Artemis N, Milonas I. Source: European Journal of Neurology : the Official Journal of the European Federation of Neurological Societies. 2002 July; 9(4): 429-30. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12099930&dopt=Abstract

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Juvenile myasthenia gravis and thymectomy: report of ten cases. Author(s): de Assis JL, Marchiori PE, Zambon AA, Scaff M. Source: Revista Do Hospital Das Clinicas. 1992 September-October; 47(5): 234-6. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=1340608&dopt=Abstract

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Juvenile myasthenia gravis with predominant facial weakness in a 7-year-old boy. Author(s): Kini PG. Source: International Journal of Pediatric Otorhinolaryngology. 1995 May; 32(2): 167-9. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=7657471&dopt=Abstract

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Juvenile myasthenia gravis with prepubertal onset. Author(s): Evoli A, Batocchi AP, Bartoccioni E, Lino MM, Minisci C, Tonali P. Source: Neuromuscular Disorders : Nmd. 1998 December; 8(8): 561-7. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10093062&dopt=Abstract

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Juvenile myasthenia gravis: treatment with immune globulin and thymectomy. Author(s): Herrmann DN, Carney PR, Wald JJ. Source: Pediatric Neurology. 1998 January; 18(1): 63-6. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=9492094&dopt=Abstract

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Laryngeal myasthenia gravis: report of 40 cases. Author(s): Mao VH, Abaza M, Spiegel JR, Mandel S, Hawkshaw M, Heuer RJ, Sataloff RT. Source: Journal of Voice : Official Journal of the Voice Foundation. 2001 March; 15(1): 122-30. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12269627&dopt=Abstract

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Late onset immunodeficiency in a patient with recurrent thymic carcinoma and myasthenia gravis. Author(s): Schmidt S, Padberg F. Source: Journal of the Neurological Sciences. 1998 May 7; 157(2): 201-5. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=9619646&dopt=Abstract

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Late-onset myasthenia gravis. Follow-up of 113 patients diagnosed after age 60. Author(s): Slesak G, Melms A, Gerneth F, Sommer N, Weissert R, Dichgans J. Source: Annals of the New York Academy of Sciences. 1998 May 13; 841: 777-80. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=9668329&dopt=Abstract

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Late-onset myasthenia gravis: a changing scene. Author(s): Aarli JA. Source: Archives of Neurology. 1999 January; 56(1): 25-7. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=9923757&dopt=Abstract

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Less is more: treatment of aggravating behaviour in myasthenia gravis patients with dysphagia. Author(s): de Swart BJ, Padberg GW, van Engelen BG. Source: European Journal of Neurology : the Official Journal of the European Federation of Neurological Societies. 2002 November; 9(6): 688-9. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12453089&dopt=Abstract

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Levamisole aids in treatment of refractory oral candidiasis in two patients with thymoma associated with myasthenia gravis: report of two cases. Author(s): Lai WH, Lu SY, Eng HL. Source: Chang Gung Med J. 2002 September; 25(9): 606-11. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12479622&dopt=Abstract

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Linkage of HLA to myasthenia gravis and genetic heterogeneity depending on antititin antibodies. Author(s): Giraud M, Beaurain G, Yamamoto AM, Eymard B, Tranchant C, Gajdos P, Garchon HJ. Source: Neurology. 2001 November 13; 57(9): 1555-60. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11706089&dopt=Abstract

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Literature review of the usefulness of repetitive nerve stimulation and single fiber EMG in the electrodiagnostic evaluation of patients with suspected myasthenia gravis or Lambert-Eaton myasthenic syndrome. Author(s): AAEM Quality Assurance Committee. American Association of Electrodiagnostic Medicine. Source: Muscle & Nerve. 2001 September; 24(9): 1239-47. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11494281&dopt=Abstract

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Localized thymic Langerhans' cell histiocytosis and its relationship with myasthenia gravis. Immunohistochemical, ultrastructural, and cytometric studies. Author(s): Gilcrease MZ, Rajan B, Ostrowski ML, Ramzy I, Schwartz MR. Source: Archives of Pathology & Laboratory Medicine. 1997 February; 121(2): 134-8. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=9126040&dopt=Abstract

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Long-term clinical outcome after transcervical thymectomy for myasthenia gravis. Author(s): Bril V, Kojic J, Ilse WK, Cooper JD. Source: The Annals of Thoracic Surgery. 1998 June; 65(6): 1520-2. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=9647051&dopt=Abstract

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Long-term cyclosporine treatment in a group of severe myasthenia gravis patients. Author(s): Bonifati DM, Angelini C. Source: Journal of Neurology. 1997 September; 244(9): 542-7. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=9352450&dopt=Abstract

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Long-term evaluation of extended thymectomy with anterior mediastinal dissection for myasthenia gravis. Author(s): Stern LE, Nussbaum MS, Quinlan JG, Fischer JE. Source: Surgery. 2001 October; 130(4): 774-8; Discussion 778-80. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11602911&dopt=Abstract

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Long-term follow-up of myasthenia gravis patients with hyperthyroidism. Author(s): Ratanakorn D, Vejjajiva A. Source: Acta Neurologica Scandinavica. 2002 August; 106(2): 93-8. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12100368&dopt=Abstract

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Long-term immunologic effects of thymectomy in patients with myasthenia gravis. Author(s): Gerli R, Paganelli R, Cossarizza A, Muscat C, Piccolo G, Barbieri D, Mariotti S, Monti D, Bistoni O, Raiola E, Venanzi FM, Bertotto A, Franceschi C. Source: The Journal of Allergy and Clinical Immunology. 1999 May; 103(5 Pt 1): 865-72. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10329821&dopt=Abstract

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Long-term prognostic analysis of thymectomized patients with myasthenia gravis. Author(s): Liu W, Tong T, Ji Z, Zhang Z. Source: Chinese Medical Journal. 2002 February; 115(2): 235-7. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11940339&dopt=Abstract

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Long-term treatment of myasthenia gravis with immunoadsorption. Author(s): Haas M, Mayr N, Zeitlhofer J, Goldammer A, Derfler K. Source: Journal of Clinical Apheresis. 2002; 17(2): 84-7. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12210711&dopt=Abstract

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Low dose interferon-alpha is safe in patients with myasthenia gravis. Author(s): Bolay H, Karabudak R, Varli K, Saribas O. Source: Journal of Neurology, Neurosurgery, and Psychiatry. 1997 March; 62(3): 302-3. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=9069506&dopt=Abstract

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Low level of TGF-beta in early stages of myasthenia gravis. Author(s): Batocchi AP, Evoli A, Lino M, Majolini L, Minisci C, Tonali P. Source: Annals of the New York Academy of Sciences. 1998 May 13; 841: 342-6. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=9668255&dopt=Abstract

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Low-dose tacrolimus for intractable myasthenia gravis. Author(s): Yoshikawa H, Mabuchi K, Yasukawa Y, Takamori M, Yamada M. Source: Journal of Clinical Neuroscience : Official Journal of the Neurosurgical Society of Australasia. 2002 November; 9(6): 627-8. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12604270&dopt=Abstract

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Lupus anticoagulant in myasthenia gravis associated with IgM gammopathy. Author(s): Ishikawa S, Komiyama Y, Kobayashi H, Tsuyuzaki J, Tokunaga S, Miyazaki A, Hanyu N, Ikeda S. Source: Intern Med. 2001 September; 40(9): 952-5. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11579964&dopt=Abstract

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Masseteric repetitive nerve stimulation in the diagnosis of myasthenia gravis. Author(s): Pavesi G, Cattaneo L, Tinchelli S, Mancia D. Source: Clinical Neurophysiology : Official Journal of the International Federation of Clinical Neurophysiology. 2001 June; 112(6): 1064-9. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11377266&dopt=Abstract

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Mature, long-lived CD4+ and CD8+ T cells are generated by the thymoma in myasthenia gravis. Author(s): Buckley C, Douek D, Newsom-Davis J, Vincent A, Willcox N. Source: Annals of Neurology. 2001 July; 50(1): 64-72. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11456312&dopt=Abstract

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Maximal respiratory pressures in myasthenia gravis. Relation to single fiber electromyography. Author(s): Fernandez CM, Tejedor ED, Frank A, Pino JM, Conde CP, Barreiro P. Source: Acta Neurologica Scandinavica. 2001 June; 103(6): 392-5. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11421852&dopt=Abstract

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Medical therapies in myasthenia gravis. Author(s): Younger DS, Raksadawan N. Source: Chest Surg Clin N Am. 2001 May; 11(2): 329-36. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11413759&dopt=Abstract

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Myasthenia gravis during low-dose IFN-alpha therapy for chronic hepatitis C. Author(s): Borgia G, Reynaud L, Gentile I, Cerini R, Ciampi R, Dello Russo M, Piazza M. Source: Journal of Interferon & Cytokine Research : the Official Journal of the International Society for Interferon and Cytokine Research. 2001 July; 21(7): 469-70. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11506739&dopt=Abstract

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Myasthenia gravis in conjunction with Graves' disease: a diagnostic challenge. Author(s): Tanwani LK, Lohano V, Ewart R, Broadstone VL, Mokshagundam SP. Source: Endocrine Practice : Official Journal of the American College of Endocrinology and the American Association of Clinical Endocrinologists. 2001 July-August; 7(4): 2758. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11497480&dopt=Abstract

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Myasthenia gravis with autoimmune autonomic neuropathy. Author(s): Vernino S, Cheshire WP, Lennon VA. Source: Autonomic Neuroscience : Basic & Clinical. 2001 May 14; 88(3): 187-92. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11474561&dopt=Abstract

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Myasthenia gravis with thymoma is more common in the Maori and Pacific Island populations in New Zealand. Author(s): Fink JN, Wallis WE, Haydock DA. Source: Internal Medicine Journal. 2001 May-June; 31(4): 206-10. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11456033&dopt=Abstract

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Myasthenia gravis, corticosteroids and osteoporosis prophylaxis. Author(s): Smith GD, Stevens DL, Fuller GN. Source: Journal of Neurology. 2001 February; 248(2): 151. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11284137&dopt=Abstract

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Myasthenia gravis. Author(s): Vincent A, Palace J, Hilton-Jones D. Source: Lancet. 2001 June 30; 357(9274): 2122-8. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11445126&dopt=Abstract

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Myasthenia gravis: an elusive diagnosis in older people. Author(s): Ngeh JK, McElligott G. Source: Journal of the American Geriatrics Society. 2001 May; 49(5): 683-4. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11380770&dopt=Abstract

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Myasthenia gravis: options and timing of immunomodulatory treatment. Author(s): Spring PJ, Spies JM. Source: Biodrugs : Clinical Immunotherapeutics, Biopharmaceuticals and Gene Therapy. 2001; 15(3): 173-83. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11437683&dopt=Abstract

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Mycophenolate (CellCept) treatment of myasthenia gravis, chronic inflammatory polyneuropathy and inclusion body myositis. Author(s): Mowzoon N, Sussman A, Bradley WG. Source: Journal of the Neurological Sciences. 2001 April 1; 185(2): 119-22. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11311292&dopt=Abstract

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Mycophenolate mofetil: a new immunosuppressive approach. Successful treatment in a case of myasthenia gravis associated with incomplete lupus erythematosus syndrome and hepatitis C virus infection. Author(s): Caponnetto C, Rossi E, Primavera A. Source: European Neurology. 2001; 46(1): 53-4. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11455187&dopt=Abstract

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Nephrotic syndrome with acute renal failure and cerebral infarction in a patient with myasthenia gravis. Author(s): Ogawa M, Tsukahara T, Saisho H. Source: American Journal of Nephrology. 1999; 19(5): 622-3. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10575195&dopt=Abstract

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Neuromyotonia and myasthenia gravis without thymoma. Author(s): Van Parijs V, Van den Bergh PY, Vincent A. Source: Journal of Neurology, Neurosurgery, and Psychiatry. 2002 September; 73(3): 344-5. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12185179&dopt=Abstract

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Neuromyotonia, peripheral neuropathy and myasthenia gravis. Author(s): Martinelli P, Patuelli A, Minardi C, Cau A, Riviera AM, Dal Pozzo F. Source: Muscle & Nerve. 1996 April; 19(4): 505-10. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=8622730&dopt=Abstract

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Neuropsychological test performance and affect in myasthenia gravis. Author(s): Bartel PR, Lotz BP. Source: Acta Neurologica Scandinavica. 1995 April; 91(4): 266-70. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=7625152&dopt=Abstract

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Nicotine-sensitive myasthenia gravis. Author(s): Moreau T, Vandenabeele S, Depierre P, Confavreux C. Source: Lancet. 1995 January 7; 345(8941): 61-2. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=7865007&dopt=Abstract

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NKT-associated markers and perforin in hyperplastic thymuses from patients with Myasthenia gravis. Author(s): Nagane Y, Utsugisawa K, Obara D, Tohgi H. Source: Muscle & Nerve. 2001 October; 24(10): 1359-64. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11562917&dopt=Abstract

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No evidence for an association of AChR beta-subunit gene (CHRNB1) with myasthenia gravis. Author(s): Djabiri F, Gajdos P, Eymard B, Gomez L, Bach JF, Garchon HJ. Source: Journal of Neuroimmunology. 1997 September; 78(1-2): 86-9. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=9307231&dopt=Abstract

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No evidence for interleukin-4 gene conferring susceptibility to myasthenia gravis. Author(s): Huang D, Xia S, Zhou Y, Pirskanen R, Liu L, Lefvert AK. Source: Journal of Neuroimmunology. 1998 December 1; 92(1-2): 208-11. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=9916896&dopt=Abstract

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Normal human immunoglobulin suppresses experimental myasthenia gravis in SCID mice. Author(s): Vassilev T, Yamamoto M, Aissaoui A, Bonnin E, Berrih-Aknin S, Kazatchkine MD, Kaveri SV. Source: European Journal of Immunology. 1999 August; 29(8): 2436-42. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10458757&dopt=Abstract

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Normalization of elevated CD4-/CD8- (double-negative) T cells after thymectomy parallels clinical remission in myasthenia gravis associated with thymic hyperplasia but not thymoma. Author(s): Reinhardt C, Melms A. Source: Annals of Neurology. 2000 October; 48(4): 603-8. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11026443&dopt=Abstract

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Ocular aspects of myasthenia gravis. Author(s): Barton JJ, Fouladvand M. Source: Seminars in Neurology. 2000; 20(1): 7-20. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10874773&dopt=Abstract

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Ocular myasthenia gravis and inflammatory bowel disease: a case report and literature review. Author(s): Foroozan R, Sambursky R. Source: The British Journal of Ophthalmology. 2003 September; 87(9): 1186-7. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12928296&dopt=Abstract

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Ocular myasthenia gravis coincident with thyroid ophthalmopathy. Author(s): Yaman A, Yaman H. Source: Neurology India. 2003 March; 51(1): 100-1. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12865535&dopt=Abstract

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Oculo-bulbar myasthenia gravis induced by cytokine treatment of a patient with metastasized renal cell carcinoma. Author(s): Rohde D, Sliwka U, Schweizer K, Jakse G. Source: European Journal of Clinical Pharmacology. 1996; 50(6): 471-3. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=8858274&dopt=Abstract

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Oculomotor signs in Lambert-Eaton myasthenic syndrome-coincidence with myasthenia gravis. Author(s): Toyka KV, Schneider-Gold C. Source: Annals of Neurology. 2003 July; 54(1): 135-6; Author Reply 136-7. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12838533&dopt=Abstract

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On the initial trigger of myasthenia gravis and suppression of the disease by antibodies against the MHC peptide region involved in the presentation of a pathogenic T-cell epitope. Author(s): Atassi MZ, Oshima M, Deitiker P. Source: Critical Reviews in Immunology. 2001; 21(1-3): 1-27. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11642597&dopt=Abstract

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Open-loop and closed-loop optokinetic nystagmus (OKN) in myasthenia gravis and nonmyasthenic subjects. Author(s): Yang Q, Wei M, Sun F, Tian J, Chen X, Lu C. Source: Experimental Neurology. 2000 November; 166(1): 166-72. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11031092&dopt=Abstract

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Ophthaproblem. Ocular myasthenia gravis. Author(s): Baxter S, Sharma S. Source: Can Fam Physician. 2002 November; 48: 1771, 1776. No Abstract Available. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12489242&dopt=Abstract

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Osteoporosis prevention in myasthenia gravis: a reminder. Author(s): Lewis SJ, Smith PE. Source: Acta Neurologica Scandinavica. 2001 May; 103(5): 320-2. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11328209&dopt=Abstract

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Outcome of thymectomy in patients with Myasthenia Gravis. Author(s): Al-Mahdawi AM, Al-Talib NM. Source: Saudi Med J. 2002 January; 23(1): 39-43. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11938362&dopt=Abstract

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Parkinson's disease associated with myasthenia gravis. A report of 4 cases. Author(s): Levin N, Karussis D, Abramsky O. Source: Journal of Neurology. 2003 June; 250(6): 766-7. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12862037&dopt=Abstract

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Perioperative management of a patient with congenital myasthenia gravis for elective caesarean section. Author(s): Koh LK, Ip-Yam PC, Tan AS. Source: Singapore Med J. 2001 February; 42(2): 061-3. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11358192&dopt=Abstract

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Perioperative medical management and outcome following thymectomy for myasthenia gravis. Author(s): Chevalley C, Spiliopoulos A, de Perrot M, Tschopp JM, Licker M. Source: Canadian Journal of Anaesthesia = Journal Canadien D'anesthesie. 2001 May; 48(5): 446-51. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11394511&dopt=Abstract

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Plasmaexchange in the treatment of myasthenia gravis associated with thymoma. Author(s): Gogovska L, Ljapcev R, Polenakovic M, Stojkovski L, Popovska M, Grcevska L. Source: Int J Artif Organs. 2003 February; 26(2): 170-3. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12653352&dopt=Abstract

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Practice parameter for repetitive nerve stimulation and single fiber EMG evaluation of adults with suspected myasthenia gravis or Lambert-Eaton myasthenic syndrome: summary statement. Author(s): AAEM Quality Assurance Committee. American Association of Electrodiagnostic Medicine. Source: Muscle & Nerve. 2001 September; 24(9): 1236-8. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11494280&dopt=Abstract

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Predictors of outcome in thymectomy for myasthenia gravis. Author(s): Budde JM, Morris CD, Gal AA, Mansour KA, Miller JI Jr. Source: The Annals of Thoracic Surgery. 2001 July; 72(1): 197-202. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11465178&dopt=Abstract

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Preoperative preparation of patients with myasthenia gravis forestalls postoperative respiratory complications after thymectomy. Author(s): Jaretzki A 3rd, Aarli JA, Kaminski HJ, Phillips LH 2nd, Sanders DB. Source: The Annals of Thoracic Surgery. 2003 March; 75(3): 1068; Author Reply 1069. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12645760&dopt=Abstract

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Prevention of passively transferred experimental autoimmune myasthenia gravis by an in vitro selected RNA aptamer. Author(s): Hwang B, Han K, Lee SW. Source: Febs Letters. 2003 July 31; 548(1-3): 85-9. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12885412&dopt=Abstract

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Prognostic factors of thymectomy in patients with myasthenia gravis: a cohort of 132 patients. Author(s): Tellez-Zenteno JF, Remes-Troche JM, Garcia-Ramos G, Estanol B, GardunoEspinoza J. Source: Annals of the New York Academy of Sciences. 2003 September; 998: 491-3. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=14592918&dopt=Abstract

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Prostatic involvement of a testicular lymphoma in a patient with myasthenia gravis on long-term azathioprine. Author(s): Barthelmes L, Thomas KJ, Seale JR. Source: Leukemia & Lymphoma. 2002 December; 43(12): 2425-6. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12613537&dopt=Abstract

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Quality of life and well-being of patients with myasthenia gravis. Author(s): Paul RH, Nash JM, Cohen RA, Gilchrist JM, Goldstein JM. Source: Muscle & Nerve. 2001 April; 24(4): 512-6. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11268023&dopt=Abstract

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Quality of life in patients with myasthenia gravis. Author(s): Padua L, Evoli A, Aprile I, Caliandro P, D'Amico P, Rabini A, Tonali P. Source: Muscle & Nerve. 2002 March; 25(3): 466-7. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11870729&dopt=Abstract

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Quantitative EMG findings at different force levels in patients with myasthenia gravis. Author(s): Lo Monaco M, Christensen H, Fuglsang-Frederiksen A. Source: Neurophysiologie Clinique = Clinical Neurophysiology. 1993 July; 23(4): 353-61. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=8332110&dopt=Abstract

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Quantitative ocular tests for myasthenia gravis: a comparative review with detection theory analysis. Author(s): Barton JJ. Source: Journal of the Neurological Sciences. 1998 February 18; 155(1): 104-14. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=9562331&dopt=Abstract

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Randomized, controlled trial of intravenous immunoglobulin in myasthenia gravis. Author(s): Wolfe GI, Barohn RJ, Foster BM, Jackson CE, Kissel JT, Day JW, Thornton CA, Nations SP, Bryan WW, Amato AA, Freimer ML, Parry GJ; Myasthenia Gravis-IVIG Study Group. Source: Muscle & Nerve. 2002 October; 26(4): 549-52. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12362423&dopt=Abstract

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Ratings of subjective mental fatigue relate to cognitive performance in patients with myasthenia gravis. Author(s): Paul RH, Cohen RA, Gilchrist JM. Source: Journal of Clinical Neuroscience : Official Journal of the Neurosurgical Society of Australasia. 2002 May; 9(3): 243-6. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12093127&dopt=Abstract

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Rationale for a T cell receptor peptide therapy in myasthenia gravis. Author(s): Jambou F, Menestrier M, Klingel-Schmitt I, Caillat-Zucman S, Aissaoui A, Berrih-Aknin S, Cohen-Kaminsky S. Source: Annals of the New York Academy of Sciences. 2003 September; 998: 320-3. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=14592890&dopt=Abstract

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RE: “Surgical correction of blepharoptosis in patients with myasthenia gravis”. Author(s): Eliasoph I. Source: Ophthalmic Plastic and Reconstructive Surgery. 2002 July; 18(4): 312-3; Author Reply 313. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12142768&dopt=Abstract

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Relapse of ocular symptoms after remission of myasthenia gravis--a comparison of relapsed and complete remission cases. Author(s): Wakata N, Iguchi H, Sugimoto H, Nomoto N, Kurihara T. Source: Clinical Neurology and Neurosurgery. 2003 April; 105(2): 75-7. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12691794&dopt=Abstract

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Repetitive hypoglossal nerve stimulation in myasthenia gravis. Author(s): Lo YL, Leoh TH, Tan YE, Foo ML, Dan YF, Ratnagopal P. Source: Clinical Neurophysiology : Official Journal of the International Federation of Clinical Neurophysiology. 2002 August; 113(8): 1227-30. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12140000&dopt=Abstract

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Repetitive stimulation of the long thoracic nerve in myasthenia gravis: clinical and electrophysiological correlations. Author(s): Lo YL, Leoh TH, Dan YF, Tan YE, Nurjannah S, Ratnagopal P. Source: Journal of Neurology, Neurosurgery, and Psychiatry. 2003 March; 74(3): 379-81. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12588934&dopt=Abstract

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Respiratory failure due to vocal cord paresis in myasthenia gravis. Author(s): Teramoto K, Kuwabara M, Matsubara Y. Source: Respiration; International Review of Thoracic Diseases. 2002; 69(3): 280-2. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12097777&dopt=Abstract

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Reversible ocular myasthenia gravis or mitochondrial myopathy from statins? Author(s): Engel WK. Source: Lancet. 2003 January 4; 361(9351): 85-6. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12517506&dopt=Abstract

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Ryanodine receptor antibodies in myasthenia gravis: epitope mapping and effect on calcium release in vitro. Author(s): Skeie GO, Mygland A, Treves S, Gilhus NE, Aarli JA, Zorzato F. Source: Muscle & Nerve. 2003 January; 27(1): 81-9. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12508299&dopt=Abstract

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Scenarios for autoimmunization of T and B cells in myasthenia gravis. Author(s): Shiono H, Roxanis I, Zhang W, Sims GP, Meager A, Jacobson LW, Liu JL, Matthews I, Wong YL, Bonifati M, Micklem K, Stott DI, Todd JA, Beeson D, Vincent A, Willcox N. Source: Annals of the New York Academy of Sciences. 2003 September; 998: 237-56. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=14592881&dopt=Abstract

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Semiquantitative measurement of acetylcholine receptor at the motor end-plate in myasthenia gravis. Author(s): Tsujihata M, Ito H, Satoh A, Yoshimura T, Motomura M, Nakamura T. Source: Intern Med. 2001 May; 40(5): 376-81. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11393405&dopt=Abstract

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Somatic hypermutation and selection of B cells in thymic germinal centers responding to acetylcholine receptor in myasthenia gravis. Author(s): Sims GP, Shiono H, Willcox N, Stott DI. Source: Journal of Immunology (Baltimore, Md. : 1950). 2001 August 15; 167(4): 1935-44. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11489973&dopt=Abstract

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Standards of measurements in myasthenia gravis. Author(s): Gajdos P, Sharshar T, Chevret S. Source: Annals of the New York Academy of Sciences. 2003 September; 998: 445-52. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=14592913&dopt=Abstract

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Standards of measurements in myasthenia gravis. Author(s): Barohn RJ. Source: Annals of the New York Academy of Sciences. 2003 September; 998: 432-9. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=14592911&dopt=Abstract

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Stimulated single-fiber EMG of the frontalis and orbicularis oculi muscles in ocular myasthenia gravis. Author(s): Valls-Canals J, Povedano M, Montero J, Pradas J. Source: Muscle & Nerve. 2003 October; 28(4): 501-3. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=14506723&dopt=Abstract

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Study of T cell receptor gene rearrangements in patients with myasthenia gravis. Author(s): Feng G, Li X, Chen Q. Source: Chinese Medical Sciences Journal = Chung-Kuo I Hsueh K'o Hsueh Tsa Chih / Chinese Academy of Medical Sciences. 2001 March; 16(1): 55. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12899351&dopt=Abstract

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Suppression of myasthenia gravis by antigen-specific mucosal tolerance and modulation of cytokines and costimulatory factors. Author(s): Souroujon MC, Maiti PK, Feferman T, Im SH, Raveh L, Fuchs S. Source: Annals of the New York Academy of Sciences. 2003 September; 998: 533-6. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=14592924&dopt=Abstract

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Surgical correction of blepharoptosis in patients with myasthenia gravis. Author(s): Bradley EA, Bartley GB, Chapman KL, Waller RR. Source: Ophthalmic Plastic and Reconstructive Surgery. 2001 March; 17(2): 103-10. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11281581&dopt=Abstract

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Systemic vasculitis and hyperthyroidism in a patient with myasthenia gravis. Author(s): Raillard-Gohin H, Leray-Moragues H, Canaud B, Pages M. Source: Journal of Neurology. 2001 June; 248(6): 525-6. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11499646&dopt=Abstract

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T cells and cytokines in the pathogenesis of acquired myasthenia gravis. Author(s): Milani M, Ostlie N, Wang W, Conti-Fine BM. Source: Annals of the New York Academy of Sciences. 2003 September; 998: 284-307. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=14592887&dopt=Abstract

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Telithromycin and myasthenia gravis. Author(s): Nieman RB, Sharma K, Edelberg H, Caffe SE. Source: Clinical Infectious Diseases : an Official Publication of the Infectious Diseases Society of America. 2003 December 1; 37(11): 1579. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=14614683&dopt=Abstract

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The epidemiology of myasthenia gravis. Author(s): Phillips LH 2nd. Source: Annals of the New York Academy of Sciences. 2003 September; 998: 407-12. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=14592908&dopt=Abstract

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The role of thymomas in the development of myasthenia gravis. Author(s): Marx A, Muller-Hermelink HK, Strobel P. Source: Annals of the New York Academy of Sciences. 2003 September; 998: 223-36. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=14592880&dopt=Abstract

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The thymus and myasthenia gravis. Author(s): Ragheb S, Lisak RP. Source: Chest Surg Clin N Am. 2001 May; 11(2): 311-27, X. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11413758&dopt=Abstract

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The use of intravenous immunoglobulin as maintenance therapy in myasthenia gravis. Author(s): Hilkevich O, Drory VE, Chapman J, Korczyn AD. Source: Clinical Neuropharmacology. 2001 May-June; 24(3): 173-6. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11391130&dopt=Abstract

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Thymectomy and antimuscle antibodies in nonthymomatous myasthenia gravis. Author(s): Romi F, Gilhus NE, Varhaug JE, Myking A, Skeie GO, Aarli JA. Source: Annals of the New York Academy of Sciences. 2003 September; 998: 481-90. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=14592917&dopt=Abstract

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Titin, thymoma, and myasthenia gravis. Author(s): Aarli JA. Source: Archives of Neurology. 2001 June; 58(6): 869-70. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11405799&dopt=Abstract

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Transcervical thymectomy for myasthenia gravis. Author(s): Meyers BF, Cooper JD. Source: Chest Surg Clin N Am. 2001 May; 11(2): 363-8. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11413761&dopt=Abstract

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Treatment principles in the management of autoimmune myasthenia gravis. Author(s): Richman DP, Agius MA. Source: Annals of the New York Academy of Sciences. 2003 September; 998: 457-72. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=14592915&dopt=Abstract

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Undiagnosed myasthenia gravis unmasked by neuromuscular blockade. Author(s): Puhringer FK, Rex C, Renner M, Kazmaier F. Source: British Journal of Anaesthesia. 2001 October; 87(4): 650-1. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11878746&dopt=Abstract

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Undiagnosed myasthenia gravis unmasked by neuromuscular blockade. Author(s): Dunsire MF, Clarke SG, Stedmon JJ. Source: British Journal of Anaesthesia. 2001 May; 86(5): 727-30. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11575353&dopt=Abstract

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Unexpected cross-reactivity between myosin and a main immunogenic region (MIR) of the acetylcholine receptor by antisera obtained from myasthenia gravis patients. Author(s): Mohan S, Barohn RJ, Krolick KA. Source: Clinical Immunology and Immunopathology. 1992 September; 64(3): 218-26. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=1643755&dopt=Abstract

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Unilateral ptosis as an initial manifestation of D-penicillamine induced myasthenia gravis. Author(s): Raynauld JP, Lee YS, Kornfeld P, Fries JF. Source: The Journal of Rheumatology. 1993 September; 20(9): 1592-3. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=8164222&dopt=Abstract

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Unmasking and exacerbation of myasthenia gravis by ophthalmic solutions: betoxolol, tobramycin, and dexamethasone. A case report. Author(s): Khella SL, Kozart D. Source: Muscle & Nerve. 1997 May; 20(5): 631. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=9140379&dopt=Abstract

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Unravelling the pathogenesis of myasthenia gravis. Author(s): Vincent A. Source: Nature Reviews. Immunology. 2002 October; 2(10): 797-804. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12360217&dopt=Abstract

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Untreated hepatitis C may provoke myasthenia gravis. Author(s): Reading PJ, Newman PK. Source: Journal of Neurology, Neurosurgery, and Psychiatry. 1998 June; 64(6): 820. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=9647325&dopt=Abstract

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Upper motor neuron dysfunction reduces the EMG evidence of myasthenia gravis. Author(s): Fiacchino F, Scaioli V, Antozzi C, Giannini A. Source: Journal of Neurosurgical Anesthesiology. 1995 July; 7(3): 178-82. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=7549369&dopt=Abstract

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Use of intravenous pulsed cyclophosphamide in severe, generalized myasthenia gravis. Author(s): De Feo LG, Schottlender J, Martelli NA, Molfino NA. Source: Muscle & Nerve. 2002 July; 26(1): 31-6. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12115946&dopt=Abstract

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Using histochemical methods to study pathological features of hyperplastic thymus and thymoma in patients with myasthenia gravis. Author(s): Tu LH, Cai GY, Zhu XM, Zhang RQ. Source: Annals of the New York Academy of Sciences. 1998 May 13; 841: 427-9. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=9668271&dopt=Abstract

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Validity and reliability of two muscle strength scores commonly used as endpoints in assessing treatment of myasthenia gravis. Author(s): Sharshar T, Chevret S, Mazighi M, Chillet P, Huberfeld G, Berreotta C, Houfani M, Gajdos P. Source: Journal of Neurology. 2000 April; 247(4): 286-90. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10836621&dopt=Abstract

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Ventilatory care in myasthenia gravis crisis: assessing the baseline adverse event rate. Author(s): Varelas PN, Chua HC, Natterman J, Barmadia L, Zimmerman P, Yahia A, Ulatowski J, Bhardwaj A, Williams MA, Hanley DF. Source: Critical Care Medicine. 2002 December; 30(12): 2663-8. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12483056&dopt=Abstract

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Vertical infraclavicular block and myasthenia gravis. Author(s): Troy AM, Kinirons B. Source: Anaesthesia. 2001 August; 56(8): 817-8. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11494426&dopt=Abstract

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Video-assisted thoracoscopic extended thymectomy and extended transsternal thymectomy (T-3b) in non-thymomatous myasthenia gravis patients: remission after 6 years of follow-up. Author(s): Mantegazza R, Baggi F, Bernasconi P, Antozzi C, Confalonieri P, Novellino L, Spinelli L, Ferro MT, Beghi E, Cornelio F. Source: Journal of the Neurological Sciences. 2003 August 15; 212(1-2): 31-6. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12809996&dopt=Abstract

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Video-assisted thoracoscopic thymectomy for myasthenia gravis. Author(s): Wright GM, Barnett S, Clarke CP. Source: Internal Medicine Journal. 2002 August; 32(8): 367-71. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12162392&dopt=Abstract

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Video-assisted thoracoscopic thymectomy for myasthenia gravis. Author(s): Yim AP, Kay RL, Ho JK. Source: Chest. 1995 November; 108(5): 1440-3. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=7587454&dopt=Abstract

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Video-assisted thoracoscopic thymectomy in juvenile myasthenia gravis. Author(s): Kolski HK, Kim PC, Vajsar J. Source: Journal of Child Neurology. 2001 August; 16(8): 569-73. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11510927&dopt=Abstract

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Video-assisted thoracoscopy thymectomy for myasthenia gravis. Author(s): Mack MJ. Source: Chest Surg Clin N Am. 2001 May; 11(2): 389-405, Xi-Xii. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11413763&dopt=Abstract

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Video-assisted thymectomy for myasthenia gravis: an update of a single institution experience. Author(s): Savcenko M, Wendt GK, Prince SL, Mack MJ. Source: European Journal of Cardio-Thoracic Surgery : Official Journal of the European Association for Cardio-Thoracic Surgery. 2002 December; 22(6): 978-83. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12467823&dopt=Abstract

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Visual vignette. Myasthenia gravis and euthyroid Grave's disease. Author(s): Barbaro D, Piazza F, Orsini P, Lapi P, Pasquini C. Source: Endocrine Practice : Official Journal of the American College of Endocrinology and the American Association of Clinical Endocrinologists. 2003 January-February; 9(1): 103. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12917100&dopt=Abstract

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Weaning from the ventilator using BiPAP in myasthenia gravis. Author(s): Rabinstein AA, Wijdicks EF. Source: Muscle & Nerve. 2003 February; 27(2): 252-3. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12548536&dopt=Abstract

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What have we learned about cognition in myasthenia gravis?: a review of methods and results. Author(s): Paul RH, Cohen RA, Zawacki T, Gilchrist JM, Aloia MS. Source: Neuroscience and Biobehavioral Reviews. 2001 January; 25(1): 75-81. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11166079&dopt=Abstract

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What's in a smile?: Quantification of the vertical smile of patients with myasthenia gravis. Author(s): Weijnen FG, van der Bilt A, Wokke JH, Kuks JB, van der Glas HW, Bosman F. Source: Journal of the Neurological Sciences. 2000 February 15; 173(2): 124-8. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10675656&dopt=Abstract

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When the Dx is myasthenia gravis. Author(s): Cunning S. Source: Rn. 2000 April; 63(4): 26-30; Quiz 31. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10808923&dopt=Abstract

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CHAPTER 2. NUTRITION AND MYASTHENIA GRAVIS Overview In this chapter, we will show you how to find studies dedicated specifically to nutrition and myasthenia gravis.

Finding Nutrition Studies on Myasthenia Gravis 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 “myasthenia gravis” (or synonyms) into the search box, and click “Go.” To narrow the search, you can also select the “Title” field.

7 Adapted from http://ods.od.nih.gov. IBIDS is produced by the Office of Dietary Supplements (ODS) at the National Institutes of Health to assist the public, healthcare providers, educators, and researchers in locating credible, scientific information on dietary supplements. IBIDS was developed and will be maintained through an interagency partnership with the Food and Nutrition Information Center of the National Agricultural Library, U.S. Department of Agriculture.

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The following information is typical of that found when using the “Full IBIDS Database” to search for “myasthenia gravis” (or a synonym): •

Focal myasthenia gravis as a paraneoplastic syndrome of canine thymoma: improvement following thymectomy. Author(s): University of Saskatchewan, Saskatoon, Saskatchewan, Canada. Source: Lainesse, M.F.C. Taylor, S.M. Myers, S.L. Haines, D. Fowler, J.D. AmericanAnimal-Hospital-Association (USA). (Mar-April 1996). volume 32(2) page 111-117.

Additional physician-oriented references include: •

Acetylcholine receptor antibody in myasthenia gravis. Author(s): Department of Neurology, Sao Paulo University Medical School, Brazil. Source: Marchiori, P E dos Reis, M Quevedo, M E Scaff, M Cossermelli, W Assis, J L de Oliveira, R M Acta-Neurol-Scand. 1989 November; 80(5): 387-9 0001-6314

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Acquired myasthenia gravis in dogs. II. Source: Dewey, C.W. Compend-contin-educ-pract-vet. Trenton, N.J. : Veterinary Learning Systems. January 1998. volume 20 (1) page 47-59. 0193-1903

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Acute effects of intravenous injection of beta-adrenoreceptor- and calcium channel at antagonists and agonists in myasthenia gravis. Author(s): Department of Clinical Neurophysiology, Karolinska Institute, Soder Hospital, Stockholm, Sweden. Source: Jonkers, I Swerup, C Pirskanen, R Bjelak, S Matell, G Muscle-Nerve. 1996 August; 19(8): 959-65 0148-639X

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Analysis of thymectomy for myasthenia gravis in older patients: a 20-year single institution experience. Author(s): Department of Surgery, The University of Rochester School of Medicine and Dentistry, NY, USA. Source: Abt, P L Patel, H J Marsh, A Schwartz, S I J-Am-Coll-Surg. 2001 April; 192(4): 459-64 1072-7515

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Binding of peptides of the human acetylcholine receptor alpha-subunit to HLA class II of patients with myasthenia gravis. Author(s): Department of Chemical Immunology, Weizmann Institute of Science, Rehovot, Israel. Source: Zisman, E Brautbar, C Sela, M Abramsky, O Battat, S Kirshner, S L Katz Levy, Y Dayan, M Mozes, E Hum-Immunol. 1995 November; 44(3): 121-30 0198-8859

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Cell-mediated immune response against titin in myasthenia gravis: evidence for the involvement of Th1 and Th2 cells. Author(s): Department of Neurology, University of Bergen, Norway. Source: Skeie, G O Bentsen, P T Freiburg, A Aarli, J A Gilhus, N E Scand-J-Immunol. 1998 January; 47(1): 76-81 0300-9475

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Cellular immunity in myasthenia gravis after thymectomy and corticosteroid therapy. Author(s): First Department of Internal Medicine, University Hospital, Fukuoka, Japan. Source: Kawanami, S Mori, S Kamei, H Oita, J Yamasaki, H Okumura, M Shimura, H Shirakusa, T Jpn-J-Med. 1990 Mar-April; 29(2): 138-45 0021-5120

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Combination chemotherapy with cyclophosphamide, adriamycin, and vincristine in malignant thymoma and myasthenia gravis. Author(s): Second Department of Medical Oncology, Metaxa Cancer Hospital, Piraeus, Greece.

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Source: Kosmidis, P A Iliopoulos, E Pentea, S Cancer. 1988 May 1; 61(9): 1736-40 0008543X •

D-penicillamine induced myasthenia gravis in rheumatoid arthritis: an unpredictable common occurrence? Author(s): Department of Medicine, Patras University School of Medicine, Greece. Source: Andonopoulos, A P Terzis, E Tsibri, E Papasteriades, C A Papapetropoulos, T Clin-Rheumatol. 1994 December; 13(4): 586-8 0770-3198

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Effects of surgical treatment in thymoma with myasthenia gravis: our experience in 103 patients. Author(s): Istituto di Patologia Speciale Chirurgica, Universita Cattolica del Sacro Cuore, Rome, Italy. Source: Crucitti, F Doglietto, G B Bellantone, R Perri, V Tommasini, O Tonali, P J-SurgOncol. 1992 May; 50(1): 43-6 0022-4790

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Enhancement of noradrenergic neural transmission: an effective therapy of myasthenia gravis: a report on 52 consecutive patients. Author(s): Section of Neuropharmacology, Instituto de Medicina Experimental, Universidad Central de Venezuela. [email protected] Source: Lechin, F van der Dijs, B Pardey Maldonado, B John, E Jimenez, V Orozco, B Baez, S Lechin, M E J-Med. 2000; 31(5-6): 333-61 0025-7850

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Epilepsy, myasthenia gravis, and effect of plasmapheresis on antiepileptic drug concentrations. Author(s): Department of Neurology, University of Kansas Medical Center, Kansas City 66103. Source: Lai, C W Leppik, I E Jenkins, D C Sood, P Arch-Neurol. 1990 January; 47(1): 66-8 0003-9942

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Gabapentin may be hazardous in myasthenia gravis. Author(s): Department of Neurology, Hadassah University Hospital, Jerusalem Israel. Source: Boneva, N Brenner, T Argov, Z Muscle-Nerve. 2000 August; 23(8): 1204-8 0148639X

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Immunosuppressive treatment of ocular myasthenia gravis. Author(s): Clinical Neuroimmunology Group, Department of Neurology, PhilippsUniversity, Rudolf-Bultmann-Strasse 8, D-35033 Marburg, Germany. Source: Tackenberg, B Hemmer, B Oertel, W H Sommer, N BioDrugs. 2001; 15(6): 369-78 1173-8804

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In myasthenia gravis, clinical and immunological improvement post-thymectomy segregate with results of in vitro antibody secretion by immunocytes. Author(s): Brain Research Centre and Division of Neurology, Department of Medicine, University of British Columbia, Vancouver, Canada. Source: Katzberg, H D Aziz, T Oger, J J-Neurol-Sci. 2002 October 15; 202(1-2): 77-83 0022-510X

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Increased frequency of euthyroid ophthalmopathy in patients with Graves' disease associated with myasthenia gravis. Author(s): Department of Endocrinology, University of Pisa, Italy. [email protected] Source: Marino, M Barbesino, G Pinchera, A Manetti, L Ricciardi, R Rossi, B Muratorio, A Braverman, L E Mariotti, S Chiovato, L Thyroid. 2000 September; 10(9): 799-802 10507256

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Influence of food on serum ambenonium concentration in patients with myasthenia gravis. Author(s): Department of Hospital Pharmacy, Tottori University Hospital, Japan. Source: Ohtsubo, K Fujii, N Higuchi, S Aoyama, T Goto, I Tatsuhara, T Eur-J-ClinPharmacol. 1992; 42(4): 371-4 0031-6970

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Inhibition of experimental autoimmune myasthenia gravis by major histocompatibility complex class II competitor peptides results not only in a suppressed but also in an altered immune response. Author(s): Institute of Infectious Diseases and Immunology, Faculty of Veterinary Medicine, Utrecht University, The Netherlands. [email protected] Source: Wauben, M H Hoedemaekers, A C Graus, Y M Wagenaar, J P van Eden, W de Baets, M H Eur-J-Immunol. 1996 December; 26(12): 2866-75 0014-2980

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Intrathecal morphine for thymectomy in a morbidly obese patient with myasthenia gravis. Author(s): Tulane University School of Medicine, New Orleans. Source: Jahr, J S Bjerke, R J J-La-State-Med-Soc. 1991 February; 143(2): 27-9 0024-6921

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Intravenous immunoglobulin monotherapy in long-term treatment of myasthenia gravis. Author(s): Trinity Lutheran Hospital, Kansas City, MO 64108, USA. Source: Wegner, B Ahmed, I Clin-Neurol-Neurosurg. 2002 December; 105(1): 3-8 03038467

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Laryngeal myasthenia gravis: report of 40 cases. Author(s): Department of Otolaryngology-Head and Neck Surgery, Thomas Jefferson University, Philadelphia, Pennsylvania, USA. Source: Mao, V H Abaza, M Spiegel, J R Mandel, S Hawkshaw, M Heuer, R J Sataloff, R T J-Voice. 2001 March; 15(1): 122-30 0892-1997

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Major review: the clinical spectrum of pediatric myasthenia gravis: blepharoptosis, ophthalmoplegia and strabismus. A report of 14 cases. Author(s): Department of Ophthalmology, Baylor College of Medicine, Texas Children's Hospital, Houston, Texas 77030, USA. [email protected] Source: McCreery, K M Hussein, M A Lee, A G Paysse, E A Chandran, R Coats, D K Binocul-Vis-Strabismus-Q. 2002 Fall; 17(3): 181-6 1088-6281

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Molecular cloning of the canine nicotinic acetylcholine receptor alpha-subunit gene and development of the ELISA method to diagnose myasthenia gravis. Source: Yoshioka, T. Uzuka, Y. Tanabe, S. Sarashina, T. Ishiguro, N. Vet-immunolimmunopathol. Amsterdam : Elsevier. December 30, 1999. volume 72 (3/4) page 315324. 0165-2427

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Myasthenia gravis after allogeneic bone marrow transplantation treated with mycophenolate mofetil monitored by peripheral blood OX40+ CD4+ T cells. Author(s): Department of Hematology and Oncology, Graduate School of Medicine, Kyoto University, Kyoto, Japan. Source: Kotani, A Takahashi, A Koga, H Morita, R Fukuyama, H Ichinohe, T Ishikawa, T Hori, T Uchiyama, T Eur-J-Haematol. 2002 Nov-December; 69(5-6): 318-20 0902-4441

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Myasthenia gravis and pipecuronium--report of two cases. Author(s): Division of Anaesthesia, King Khalid University Hospital, Saudi Arabia. Source: Naguib, M Sari Kouzel, A Ashour, M Seraj, M Messahel, F Middle-East-JAnesthesiol. 1992 February; 11(4): 381-90 0544-0440

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Myasthenia gravis associated with cutaneous lymphoma in a dog. Author(s): Department of Veterinary Clinical Studies, Royal Dick School of Veterinary Studies, The University of Edinburgh Hospital for Small Animals, Easter Bush Veterinary Centre, Roslin, Midlothian. Source: Ridyard, A E Rhind, S M French, A T Munro, E A Hill, P B J-Small-Anim-Pract. 2000 August; 41(8): 348-51 0022-4510

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Myasthenia gravis in conjunction with Graves' disease: a diagnostic challenge. Author(s): Division of Endocrinology and Metabolism, University of Louisville, Louisville, Kentucky, USA. Source: Tanwani, L K Lohano, V Ewart, R Broadstone, V L Mokshagundam, S P EndocrPract. 2001 Jul-August; 7(4): 275-8 1530-891X

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Myasthenia gravis. A well-understood neuromuscular disorder. Author(s): Virginia Mason Medical Center, Seattle, WA 98111. Source: Ravits, J Postgrad-Med. 1988 January; 83(1): 219-23 0032-5481

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Myasthenia gravis: effect of immunoactive therapies. Author(s): Jahn Ferenc Teaching Hospital, Department of Neurology and Intensive Care Unit, Budapest. Source: Fornadi, L Horvath, R Bardosi, Z Szobor, A Acta-Med-Hung. 1994; 50(1-2): 83-92 0236-5286

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Neurophysiological evaluation in myasthenia gravis. A comprehensive study of a complete patient population. Author(s): Department of Neurology, National Hosptial (Rigshospitalet), University of Copenhagen, Denmark. Source: Somnier, F E Trojaborg, W Electroencephalogr-Clin-Neurophysiol. 1993 April; 89(2): 73-87 0013-4694

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Osteoporosis prevention in myasthenia gravis: a reminder. Author(s): Department of Neurology, University Hospital of Wales, Cardiff, UK. Source: Lewis, S J Smith, P E Acta-Neurol-Scand. 2001 May; 103(5): 320-2 0001-6314

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Passive transfer of myasthenia gravis by immunoglobulins: lack of correlation between AChR with antibody bound, acetylcholine receptor loss and transmission defect. Author(s): Department of Neurological Science, Royal Free Hospital School of Medicine, London, U.K. Source: Mossman, S Vincent, A Newsom Davis, J J-Neurol-Sci. 1988 March; 84(1): 15-28 0022-510X

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Plasmapheresis in severe forms of myasthenia gravis. Author(s): Clinica Chirurgica, Universita Tor Vergata, Rome, Italy. Source: Morosetti, M Meloni, C Iani, C Caramia, M Galderisi, C Palombo, G Gallucci, M T Bernardi, G Casciani, C U Artif-Organs. 1998 February; 22(2): 129-34 0160-564X

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Pokeweed mitogen-induced immunoglobulin secretory responses of thymic B cells in myasthenia gravis: selective secretion of IgG versus IgM cannot be explained by helper functions of thymic T cells. Author(s): Department of Medicine, University of Pennsylvania School of Medicine, Philadelphia 19104. Source: Levinson, A I Zweiman, B Lisak, R P Clin-Immunol-Immunopathol. 1990 November; 57(2): 211-7 0090-1229

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Prognostic factors of thymectomy in patients with myasthenia gravis: a cohort of 132 patients. Author(s): Department of Neurology, Instituto Nacional de Ciencias Medicas y Nutricion, Salvador Zubiran, Mexico City, Mexico. [email protected] Source: Tellez Zenteno, J F Remes Troche, J M Garcia Ramos, G Estanol, B Garduno Espinoza, J Eur-Neurol. 2001; 46(4): 171-7 0014-3022

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Reduced sulphoxidation capacity in D-penicillamine induced myasthenia gravis. Author(s): Department of Internal Medicine, Karolinska Institute, Danderyd, Sweden. Source: Seideman, P Ayesh, R Clin-Rheumatol. 1994 September; 13(3): 435-7 0770-3198

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Responses of intercostal muscle biopsies from normal subjects and patients with myasthenia gravis. Author(s): Department of Medicine, Maimonides Medical Center, Brooklyn, NY 11219. Source: Pagala, M K NandakuMarch, N V Venkatachari, S A Ravindran, K Namba, T Grob, D Muscle-Nerve. 1990 November; 13(11): 1012-22 0148-639X

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Studies on lymphocyte subsets in thymic tissue and functions of peripheral lymphocytes in patients with tumorous thymus with special reference to myasthenia gravis. Author(s): Department of Pathology, Saitama Cancer Center, Japan. Source: Tanino, M Koide, O Shimazu, A Suzuki, K Yoshimatsu, H Acta-Pathol-Jpn. 1988 April; 38(4): 425-34 0001-6632

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Successful treatment of a patient with severe refractory myasthenia gravis using mycophenolate mofetil. Author(s): Department of Neurology, University of South Florida, Tampa, USA. Source: Hauser, R A Malek, A R Rosen, R Neurology. 1998 September; 51(3): 912-3 00283878

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Suspected congenital myasthenia gravis in Brahman calves. Author(s): Department of Medicine, Faculty of Veterinary Science, University of Pretoria, Onderstepoort, South Africa. Source: Thompson, P N Vet-Rec. 1998 November 7; 143(19): 526-9 0042-4900

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T-cell vaccination in experimental myasthenia gravis: a double-edged sword. Author(s): Johns Hopkins University, School of Medicine, Baltimore, Maryland 21205. Source: Kahn, C R McIntosh, K R Drachman, D B J-Autoimmun. 1990 December; 3(6): 659-69 0896-8411

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The relationship of age to outcome in myasthenia gravis. Author(s): Department of Neurology, University of Colorado Health Sciences Center, Denver 80262. Source: Donaldson, D H Ansher, M Horan, S Rutherford, R B Ringel, S P Neurology. 1990 May; 40(5): 786-90 0028-3878

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The treatment of patients with myasthenia gravis. Author(s): Department of Medicine, Duke University Medical School, Durham, North Carolina. Source: Sanders, D B Scoppetta, C Neurol-Clin. 1994 May; 12(2): 343-68 0733-8619

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The treatment of severe forms of myasthenia gravis. Author(s): Clinic of Neurology, University Tor Vergata, Rome, Italy. Source: Iani, C Caramia, M Morosetti, M Loberti, M Palmieri, M G Meloni, C Gallucci, M T Casciani, C U Bernardi, G Funct-Neurol. 1998 Jul-September; 13(3): 231-7 0393-5264

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Therapeutic strategies for myasthenia gravis. Author(s): Department of Clinical Pharmacy, School of Pharmacy, Duquesne University, Pittsburgh, PA 15219. Source: Keys, P A Blume, R P DICPage 1991 October; 25(10): 1101-8 1042-9611

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Treatment of acquired myasthenia gravis associated with thymoma in two dogs. Author(s): Department of Small Animal Medicine and Surgery, Royal Veterinary College, Hatfield, Hertfordshire. Source: Rusbridge, C White, R N Elwood, C M Wheeler, S J J-Small-Anim-Pract. 1996 August; 37(8): 376-80 0022-4510

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Treatment of myasthenia gravis with mycophenolate mofetil: a case report. Author(s): Rush-Presbyterian-St. Luke's Medical Center, Section of Neuromuscular Disorders, Department of Neurological Sciences, Chicago, Illinois 60612, USA. [email protected] Source: Meriggioli, M N Rowin, J Muscle-Nerve. 2000 August; 23(8): 1287-9 0148-639X

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Treatment of passively transferred experimental autoimmune myasthenia gravis using papain. Author(s): Department of Biochemistry, Hellenic Pasteur Institute, Athens, Greece. Source: Poulas, K Tsouloufis, T Tzartos, S J Clin-Exp-Immunol. 2000 May; 120(2): 363-8 0009-9104

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Use of intravenous pulsed cyclophosphamide in severe, generalized myasthenia gravis. Author(s): Hospital Maria Ferrer, Buenos Aires, Argentina. Source: Gustavo de Feo, Lucas Schottlender, Juan Martelli, Nestor A Molfino, Nestor A Muscle-Nerve. 2002 July; 26(1): 31-6 0148-639X

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V beta-specific immunotoxin selectively kills acetylcholine receptor-reactive T lymphocytes from mice with experimental autoimmune myasthenia gravis. Author(s): Department of Microbiology, University of Texas Health Science Center at San Antonio 78284. Source: Thompson, P A McAtee, R Infante, A J Currier, P Beninati, W Krolick, K A IntImmunol. 1994 December; 6(12): 1807-15 0953-8178

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Variable corticosteroid sensitivity of thymic cortex and medullary peripheral-type lymphoid tissue in myasthenia gravis patients: structural and functional effects. Author(s): Department of Neurological Science, Royal Free Hospital School of Medicine, London. Source: Willcox, N Schluep, M Sommer, N Campana, D Janossy, G Brown, A N Newsom Davis, J Q-J-Med. 1989 November; 73(271): 1071-87 0033-5622

Federal Resources on Nutrition In addition to the IBIDS, the United States Department of Health and Human Services (HHS) and the United States Department of Agriculture (USDA) provide many sources of information on general nutrition and health. Recommended resources include: •

healthfinder®, HHS’s gateway to health information, including diet and nutrition: http://www.healthfinder.gov/scripts/SearchContext.asp?topic=238&page=0

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The United States Department of Agriculture’s Web site dedicated to nutrition information: www.nutrition.gov

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The Food and Drug Administration’s Web site for federal food safety information: www.foodsafety.gov

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The National Action Plan on Overweight and Obesity sponsored by the United States Surgeon General: http://www.surgeongeneral.gov/topics/obesity/

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The Center for Food Safety and Applied Nutrition has an Internet site sponsored by the Food and Drug Administration and the Department of Health and Human Services: http://vm.cfsan.fda.gov/

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Center for Nutrition Policy and Promotion sponsored by the United States Department of Agriculture: http://www.usda.gov/cnpp/

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Food and Nutrition Information Center, National Agricultural Library sponsored by the United States Department of Agriculture: http://www.nal.usda.gov/fnic/

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Food and Nutrition Service sponsored by the United States Department of Agriculture: http://www.fns.usda.gov/fns/

Additional Web Resources A number of additional Web sites offer encyclopedic information covering food and nutrition. The following is a representative sample: •

AOL: http://search.aol.com/cat.adp?id=174&layer=&from=subcats

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Family Village: http://www.familyvillage.wisc.edu/med_nutrition.html

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Google: http://directory.google.com/Top/Health/Nutrition/

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Healthnotes: http://www.healthnotes.com/

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Open Directory Project: http://dmoz.org/Health/Nutrition/

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Yahoo.com: http://dir.yahoo.com/Health/Nutrition/

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WebMDHealth: http://my.webmd.com/nutrition

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WholeHealthMD.com: http://www.wholehealthmd.com/reflib/0,1529,00.html

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CHAPTER 3. ALTERNATIVE MEDICINE AND MYASTHENIA GRAVIS Overview In this chapter, we will begin by introducing you to official information sources on complementary and alternative medicine (CAM) relating to myasthenia gravis. At the conclusion of this chapter, we will provide additional sources.

National Center for Complementary and Alternative Medicine The National Center for Complementary and Alternative Medicine (NCCAM) of the National Institutes of Health (http://nccam.nih.gov/) has created a link to the National Library of Medicine’s databases to facilitate research for articles that specifically relate to myasthenia gravis 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 “myasthenia gravis” (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 myasthenia gravis: •

A comparison of stapedial reflex fatigue with repetitive stimulation and single-fiber EMG in myasthenia gravis. Author(s): Kramer LD, Ruth RA, Johns ME, Sanders DB. Source: Annals of Neurology. 1981 June; 9(6): 531-6. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=6266332&dopt=Abstract

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Acupuncture anesthesia in thymectomy on myasthenia gravis patients. Author(s): Dong ST, Nguyen VT, Nguyen VT, Vu TA, Pham MH. Source: Acupuncture & Electro-Therapeutics Research. 1988; 13(1): 25-30. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=2898196&dopt=Abstract

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Acute effects of verapamil on neuromuscular transmission in patients with myasthenia gravis. Author(s): Lee SC, Ho ST. Source: Proc Natl Sci Counc Repub China B. 1987 July; 11(3): 307-12. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=2827211&dopt=Abstract

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An elusive weakness: myasthenia gravis. Author(s): O'Donnell L. Source: Medsurg Nursing : Official Journal of the Academy of Medical-Surgical Nurses. 1996 February; 5(1): 44-9. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=8696408&dopt=Abstract

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Antigen-gelonin conjugates. Preparation and application in experimental myasthenia gravis. Author(s): Brust S, Filipp G, Hofmann U, Kalies I, Peper K, Rajki K, Sterz RK, Trommer WE. Source: Biol Chem Hoppe Seyler. 1987 August; 368(8): 991-9. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=3663331&dopt=Abstract

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Antigen-specific therapy of experimental myasthenia gravis with acetylcholine receptor-gelonin conjugates in vivo. Author(s): Urbatsch IL, Sterz RK, Peper K, Trommer WE. Source: European Journal of Immunology. 1993 March; 23(3): 776-9. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=8449224&dopt=Abstract

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Audiotympanometric findings in myasthenia gravis. Author(s): Morioka WT, Neff PA, Boisseranc TE, Hartman PW, Cantrell RW. Source: Arch Otolaryngol. 1976 April; 102(4): 211-3. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=1267704&dopt=Abstract

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Changes in biochemical properties of isolated human skeletal myofibrils with age and in Myasthenia gravis. Author(s): Matsuki H, Takeda Y, Tonomura Y. Source: Journal of Biochemistry. 1966 February; 59(2): 122-5. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=4223317&dopt=Abstract

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Chiropractic care of a pediatric patient with myasthenia gravis. Author(s): Alcantara J, Plaugher G, Araghi HJ. Source: Journal of Manipulative and Physiological Therapeutics. 2003 July-August; 26(6): 390-4. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12902968&dopt=Abstract

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Chiropractic management of a patient with myasthenia gravis and vertebral subluxations. Author(s): Alcantara J, Steiner DM, Plaugher G, Alcantara J. Source: Journal of Manipulative and Physiological Therapeutics. 1999 June; 22(5): 333-40. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10395436&dopt=Abstract

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Combination chemotherapy with cyclophosphamide, adriamycin, and vincristine in malignant thymoma and myasthenia gravis. Author(s): Kosmidis PA, Iliopoulos E, Pentea S. Source: Cancer. 1988 May 1; 61(9): 1736-40. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=3355974&dopt=Abstract

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Curare sensitivity in myasthenia gravis. Author(s): Fillmore RB, Herren AL, Pirlo AF. Source: Anesthesia and Analgesia. 1978 July-August; 57(4): 515-6. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=568417&dopt=Abstract

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Discussion about myasthenia gravis and the spleen-kidney theory. Author(s): Li GH. Source: J Tradit Chin Med. 1986 March; 6(1): 48-51. No Abstract Available. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=3736102&dopt=Abstract

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Effects of resistance exercise and creatine supplementation on myasthenia gravis: a case study. Author(s): Stout JR, Eckerson JM, May E, Coulter C, Bradley-Popovich GE. Source: Medicine and Science in Sports and Exercise. 2001 June; 33(6): 869-72. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11404649&dopt=Abstract

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Exacerbation of a case of myasthenia gravis during therapeutic electric stimulation. Author(s): Pease WS, Lagattuta FP. Source: Archives of Physical Medicine and Rehabilitation. 1987 September; 68(9): 568-70. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=3498464&dopt=Abstract

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Germine mono- and diacetate in myasthenia gravis. Author(s): Flacke WE, Blume RP, Scott WR, Foldes FF, Osserman KE. Source: Annals of the New York Academy of Sciences. 1971 September 15; 183: 316-33. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=5287830&dopt=Abstract

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High-dose immunoglobulin for juvenile myasthenia gravis. Author(s): Maruyama Y, Takeshita S, Sekine I, Yoshioka S.

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Source: Acta Paediatr Jpn. 1989 October; 31(5): 544-8. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=2515731&dopt=Abstract •

Inhibition of myosin ATPase activity by human myasthenia gravis antibodies reactive with the acetylcholine receptor. Author(s): Mohan S, Krolick KA. Source: Febs Letters. 1993 February 22; 318(1): 50-2. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=8436225&dopt=Abstract

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Masseteric repetitive nerve stimulation in the diagnosis of myasthenia gravis. Author(s): Pavesi G, Cattaneo L, Tinchelli S, Mancia D. Source: Clinical Neurophysiology : Official Journal of the International Federation of Clinical Neurophysiology. 2001 June; 112(6): 1064-9. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11377266&dopt=Abstract

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Myasthenia gravis and arrows of fortune. Author(s): Morowitz HJ. Source: Hosp Pract (Off Ed). 1986 March 15; 21(3): 179-82, 184, 189-90 Passim. No Abstract Available. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=3005351&dopt=Abstract

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Myasthenia gravis associated with hyperthyroidism in childhood. Author(s): Schlezinger NS, Corin MS. Source: Neurology. 1968 December; 18(12): 1217-22. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=5750705&dopt=Abstract

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Myasthenia gravis following iron chelation therapy with intravenous desferrioxamine. Author(s): Krishnan K, Trobe JD, Adams PT. Source: European Journal of Haematology. 1995 August; 55(2): 138-9. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=7628591&dopt=Abstract

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Myasthenia gravis in a Nigerian. Author(s): Idowu CA. Source: West Afr Med J Niger Pract. 1967 June; 16(3): 96. No Abstract Available. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=6046802&dopt=Abstract

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Myasthenia gravis presenting during general anaesthesia for oesophagoscopy--a cautionary tale. Author(s): Prior AJ, Swanston AR.


Source: The Journal of Laryngology and Otology. 1994 July; 108(7): 599-600. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=7930902&dopt=Abstract •

Myasthenia gravis. Author(s): Keesey J. Source: Archives of Neurology. 1998 May; 55(5): 745-6. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=9605737&dopt=Abstract

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Myasthenia gravis. Author(s): Koopman WJ. Source: Axone. 1990 June; 11(4): 92-3. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=2375933&dopt=Abstract

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Newer drugs for myasthenia gravis; a microphysiologic study of effects. Author(s): Hofmann WW. Source: The Journal of Pharmacology and Experimental Therapeutics. 1968 April; 160(2): 349-59. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=5647303&dopt=Abstract

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Phrenic and intercostal repetitive nerve stimulation: a useful electroneurophysiological method to detect the respiratory status of myasthenia gravis patients. Author(s): Zhuang L, Tang X, Fan D, Xu X, Wang X, Jiang J. Source: Electromyogr Clin Neurophysiol. 2003 January-February; 43(1): 9-16. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12613135&dopt=Abstract

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Plasmapheresis in myasthenia gravis. Author(s): Dau PC. Source: Prog Clin Biol Res. 1982; 88: 265-85. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=7100216&dopt=Abstract

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Regulatory action of Astragalus saponins and buzhong yiqi compound on synthesis of nicotinic acetylcholine receptor antibody in vitro for myasthenia gravis. Author(s): Tu LH, Huang DR, Zhang RQ, Shen Q, Yu YY, Hong YF, Li GH. Source: Chinese Medical Journal. 1994 April; 107(4): 300-3. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=8088200&dopt=Abstract

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Respiratory muscle training in patients with moderate to severe myasthenia gravis. Author(s): Weiner P, Gross D, Meiner Z, Ganem R, Weiner M, Zamir D, Rabner M.

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Source: The Canadian Journal of Neurological Sciences. Le Journal Canadien Des Sciences Neurologiques. 1998 August; 25(3): 236-41. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=9706726&dopt=Abstract •

Sensitivity to curare by a patient with undiagnosed myasthenia gravis syndrome. Author(s): Sanger BA, Kinyon GE. Source: Anesthesiology. 1966 May-June; 27(3): 325-8. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=5937174&dopt=Abstract

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Sites of action of gerine diacetate in myasthenia gravis. Author(s): Flacke W, Caviness VS Jr, Samaha F, Schwab RS. Source: Trans Am Neurol Assoc. 1967; 92: 158-62. No Abstract Available. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=5634017&dopt=Abstract

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Stapedius reflex decay in myasthenia gravis. Author(s): Warren WR, Gutmann L, Cody RC, Flowers P, Segal AT. Source: Archives of Neurology. 1977 August; 34(8): 496-7. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=889483&dopt=Abstract

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The role of intrapartum vibroacoustic stimulation in the prediction of neonatal myasthenia gravis. Author(s): Orvieto R, Levy T, Peleg D, Ben-Rafael Z. Source: Medical Hypotheses. 1994 February; 42(2): 129-30. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=8022331&dopt=Abstract

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The stapedius reflex in the diagnosis of myasthenia gravis. Author(s): Blom S, Zakrisson JE. Source: Journal of the Neurological Sciences. 1974 January; 21(1): 71-6. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=4443816&dopt=Abstract

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Thymic lesions in patients with myasthenia gravis: characterization with thallium 201 scintigraphy. Author(s): Higuchi T, Taki J, Kinuya S, Yamada M, Kawasuji M, Matsui O, Nonomura A, Bunko H, Tonami N. Source: Radiology. 2001 October; 221(1): 201-6. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11568341&dopt=Abstract

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Treatment of myasthenia gravis with germine diacetate. Author(s): Flacke W, Caviness VS Jr, Samaha FG. Source: The New England Journal of Medicine. 1966 December 1; 275(22): 1207-14. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=5921854&dopt=Abstract


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Treatment of myasthenia gravis. Author(s): Flacke W. Source: The New England Journal of Medicine. 1973 January 4; 288(1): 27-31. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=4347296&dopt=Abstract

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Treatment of severe myasthenia gravis with large doses of ACTH. Author(s): von Reis G, Liljestrand A, Matell G. Source: Annals of the New York Academy of Sciences. 1966 January 26; 135(1): 409-16. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=4287550&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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Chinese Medicine: http://www.newcenturynutrition.com/

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drkoop.com: http://www.drkoop.com/InteractiveMedicine/IndexC.html

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Family Village: http://www.familyvillage.wisc.edu/med_altn.htm

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Google: http://directory.google.com/Top/Health/Alternative/

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Healthnotes: http://www.healthnotes.com/

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MedWebPlus: http://medwebplus.com/subject/Alternative_and_Complementary_Medicine

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Open Directory Project: http://dmoz.org/Health/Alternative/

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HealthGate: http://www.tnp.com/

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WebMDHealth: http://my.webmd.com/drugs_and_herbs

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WholeHealthMD.com: http://www.wholehealthmd.com/reflib/0,1529,00.html

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Yahoo.com: http://dir.yahoo.com/Health/Alternative_Medicine/

The following is a specific Web list relating to myasthenia gravis; 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 Diabetes Mellitus Source: Integrative Medicine Communications; www.drkoop.com

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Herbs and Supplements Astragalus Sp Alternative names: Vetch, Rattlepod, Locoweed; Astragalus sp. Source: Alternative Medicine Foundation, Inc.; www.amfoundation.org Reishi Source: Prima Communications, Inc.www.personalhealthzone.com

General References A good place to find general background information on CAM is the National Library of Medicine. It has prepared within the MEDLINEplus system an information topic page dedicated to complementary and alternative medicine. To access this page, go to the MEDLINEplus site at http://www.nlm.nih.gov/medlineplus/alternativemedicine.html. This Web site provides a general overview of various topics and can lead to a number of general sources.

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CHAPTER 4. DISSERTATIONS ON MYASTHENIA GRAVIS Overview In this chapter, we will give you a bibliography on recent dissertations relating to myasthenia gravis. 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 “myasthenia gravis” (or a synonym) in their titles. To accurately reflect the results that you might find while conducting research on myasthenia gravis, we have not necessarily excluded non-medical dissertations in this bibliography.

Dissertations on Myasthenia Gravis 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 myasthenia gravis. 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: •

Measurement of Fatigue in Myasthenia Gravis Patients by Kittiwatanapaisan, Waraluk; DSN from The University of Alabama at Birmingham, 2002, 132 pages http://wwwlib.umi.com/dissertations/fullcit/3066319

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Spouses' Perceptions of the Impact of Myasthenia Gravis on Marital Interaction by Silberman, Jayne M., DSW from New York University, 1985, 191 pages http://wwwlib.umi.com/dissertations/fullcit/8522083

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The Effect of Whole-body Cooling on Physical Performance in Patients with Generalized Myasthenia Gravis by Mermier, Christine Mariam; PhD from The University of New Mexico, 2003, 120 pages http://wwwlib.umi.com/dissertations/fullcit/3093055

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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 MYASTHENIA GRAVIS Overview In this chapter, we will show you how to keep informed of the latest clinical trials concerning myasthenia gravis.

Recent Trials on Myasthenia Gravis The following is a list of recent trials dedicated to myasthenia gravis.8 Further information on a trial is available at the Web site indicated. •

Randomized Study of Intravenous Immunoglobulin in Patients with Mild or Moderate Myasthenia Gravis Condition(s): Myasthenia Gravis Study Status: This study is no longer recruiting patients. Sponsor(s): FDA Office of Orphan Products Development; University of Texas Purpose - Excerpt: Objectives: I. Determine whether intravenous immunoglobulin is an effective therapy for patients with mild or moderate myasthenia gravis. Study Type: Interventional Contact(s): see Web site below Web Site: http://clinicaltrials.gov/ct/show/NCT00004682

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 8

These are listed at www.ClinicalTrials.gov.

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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 “myasthenia gravis” (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 MYASTHENIA GRAVIS 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 “myasthenia gravis” (or a synonym) in their titles. To accurately reflect the results that you might find while conducting research on myasthenia gravis, we have not necessarily excluded non-medical patents in this bibliography.

Patents on Myasthenia Gravis By performing a patent search focusing on myasthenia gravis, 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. 9Adapted from the United States Patent and Trademark Office: http://www.uspto.gov/web/offices/pac/doc/general/whatis.htm.

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The following is an example of the type of information that you can expect to obtain from a patent search on myasthenia gravis: •

Assay for myasthenia gravis Inventor(s): Lindstrom; Jon M. (Del Mar, CA) Assignee(s): The Salk Institute for Biological Studies (San Diego, CA) Patent Number: 4,033,722 Date filed: August 8, 1975 Abstract: A serum assay system for diagnosis of myasthenia gravis. The assay system includes a complex of acetylcholine receptor protein and a toxin labeled with a radioactive isotope. The complex is incubated with a serum sample from a patient. During incubation, antibodies engendered by myasthenia gravis bind to receptor sites in the complex. The resulting complex containing the antibodies is precipitated by addition of anti-immunoglobulin. Radioactivity in the resulting precipitate is measured and compared with a control. Excerpt(s): The present invention relates generally to a biochemical assay system for use in medical diagnosis. More particularly, the present invention relates to a bio-assay for myasthenia gravis and to the diagnosis of myasthenia gravis in humans. Myasthenia gravis is a disease characterized by muscular weakness which particularly affects the muscles of the face, tongue and neck. Myasthenia gravis is commonly mistaken for other pathological and neurological disorders. Electromyogram response to repeated electrical nerve stimulation has been the best available diagnostic test for myasthenia gravis. However, electromyogram testing is not wholly satisfactory since this technique must be performed and evaluated by a specialized neurologist, and the effects observed are small. It would be desirable to provide a more reliable diagnostic test for determination of myasthenia gravis and one that would be accessible to any physician simply by assay of a sample of the patients serum in a clinical laboratory. Also, it would be especially desirable to have an easy method to assay patients response to immunosuppressive therapy. Accordingly, it is a principal object of the present invention to provide a serum-assay system for diagnosis of myasthenia gravis. It is another object of the invention to provide a diagnostic method for determination of myasthenia gravis which is highly selective and which can distinguish myasthenia gravis from other diseases. Web site: http://www.delphion.com/details?pn=US04033722__

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Assays for myasthenia gravis Inventor(s): Lindstrom; Jon M. (Del Mar, CA) Assignee(s): The Salk Institute for Biological Studies (San Diego, CA) Patent Number: 5,041,389 Date filed: May 29, 1990 Abstract: Improved asssays are provided for anti-acetylcholine receptor protein autoantibodies in the sera of patients with myasthenia gravis. The basis for the improved assays is the discovery that large quantities of acetylcholine receptor protein, that, for practical purposes in immunoassays, is immunologically indistinguishable

Patents 101

from human muscle acetylcholine receptor protein, can be isolated from cells of the human medullablastoma-derived cell line TE671. Excerpt(s): The present invention relates to immunochemical assays for diagnosis of myasthenia gravis. Myasthenia gravis is an autoimmune disease. In a patient suffering from the disease, autoantibodies are generated against epitopes on acetylcholine receptors at neuromuscular junctions. This autoimmune response impairs neuromuscular transmission. This impairment causes the muscular weakness and fatigability which characterize the disease. In my patents, U.S. Pat. Nos. 4,202,875 and RE 30,059, both of which are incorporated herein by reference, biochemical assays for the diagnosis of myasthenia gravis are described. Web site: http://www.delphion.com/details?pn=US05041389__ •

Benzene butyric acids and their derivatives as inhibitors of matrix metalloproteinases Inventor(s): Purchase, Jr.; Claude Forsey (Ann Arbor, MI), Roth; Bruce David (Plymouth, MI), White; Andrew David (Pinckney, MI) Assignee(s): Warner-Lambert Company (Morris Plains, NJ) Patent Number: 6,541,521 Date filed: July 12, 1999 Abstract: Benzene butyric acid compounds and derivatives are described as well as methods for the preparation and pharmaceutical compositions of same, which are useful as inhibitors of matrix metalloproteinases, particularly gelatinase A, collagenase-3, and stromelysin-1 and for the treatment of multiple sclerosis, atherosclerotic plaque rupture, aortic aneurysm, heart failure, left ventricular dilation, restenosis, periodontal disease, corneal ulceration, treatment of burns, decubital ulcers, wound healing, cancer, inflammation, pain, arthritis, osteoporosis, renal disease, or other autoimmune or inflammatory disorders dependent upon tissue invasion by leukocytes or other activated migrating cells, acute and chronic neurodegenerative disorders including stroke, head trauma, spinal cord injury, Alzheimer's disease, amyotrophic lateral sclerosis, cerebral amyloid angiopathy, AIDS, Parkinson's disease, Huntington's disease, prion diseases, myasthenia gravis, and Duchenne's muscular dystrophy. Excerpt(s): The present invention relates to novel benzene butyric acid compounds and their derivatives useful as pharmaceutical agents, to methods for their production, to pharmaceutical compositions which include these compounds and a pharmaceutically acceptable carrier, and to pharmaceutical methods of treatment. The novel compounds of the present invention are inhibitors of matrix metalloproteinases, e.g., gelatinase A (MMP-2), collagenase-3 (MMP-13), and stromelysin-1 (MMP-3). More particularly, the novel compounds of the present invention are useful in the treatment of atherosclerotic plaque rupture, aortic aneurism, heart failure, left ventricular dilation, restenosis, periodontal disease, corneal ulceration, treatment of bums, decubital ulcers, wound repair, cancer, inflammation, pain, arthritis, osteoporosis, multiple sclerosis, renal disease, and other autoimmune or inflammatory disorders dependent on the tissue invasion of leukocytes or other activated migrating cells. Additionally, the compounds of the present invention are useful in the treatment of acute and chronic neurodegenerative disorders including stroke, head trauma, spinal cord injury, Alzheimer's disease, amyotrophic lateral sclerosis, cerebral amyloid angiopathy, AIDS, Parkinson's disease, Huntington's disease, prion diseases, myasthenia gravis, and Duchenne's muscular dystrophy. Gelatinase A and stromelysin-1 are members of the


matrix metalloproteinase (MMP) family (Woessner J. F., FASEB J., 1991;5:2145-2154). Other members include fibroblast collagenase, neutrophil collagenase, gelatinase B (92 kDa gelatinase), stromelysin-2, stromelysin-3, matrilysin, collagenase 3 (Freije J. M., Diez-Itza I., Balbin M., Sanchez L. M., Blasco R., Tolivia J., and Lopez-Otin C., J. Biol. Chem., 1994;269:16766-16773), and the newly discovered membrane-associated matrix metalloproteinases (Sato H., Takino T., Okada Y., Cao J., Shinagawa A., Yamamoto E., and Seiki M., Nature, 1994;370:61-65). The catalytic zinc in matrix metalloproteinases is a focal point for inhibitor design. The modification of substrates by introducing chelating groups has generated potent inhibitors such as peptide hydroxymates and thiolcontaining peptides. Peptide hydroxamates and the natural endogenous inhibitors of MMPs (TIMPs) have been used successfully to treat animal models of cancer and inflammation. Web site: http://www.delphion.com/details?pn=US06541521__ •

Carbamates related to (-)-physostigmine as cholinergic agents Inventor(s): Atack; John R. (Bethesda, MD), Brossi; Arnold (Bethesda, MD), Rapoport; Stanley I. (Washington, DC), Yu; Qian-Sheng (Washington, DC) Assignee(s): The United States of America as represented by the Department of Health (Washington, DC) Patent Number: 4,900,748 Date filed: March 4, 1988 Abstract: Highly potent analogs of (-)-physostigmine are provided which are potent inhibitors of acetylcholinesterase and butyrylcholinesterase. These compounds are useful in treatment of glaucoma, Alzheimer's disease, myasthenia gravis, and organophosphate poisoning. Excerpt(s): The present invention relates to improvements in the treatment of diseases, and more particularly to compounds which are potent inhibitors of acetylcholinesterase and butyrylcholinesterase. Physostigmine, also called esrine, and certain of its derivatives are well known anticholinesterase inhibitors, and are useful in the treatment of glaucoma, Myasthenia Gravis, Alzheimer's disease, and as an antidote against poisoning with organophosphates. Physostigmine was first isolated in 1864 by Jobst and Hesse after it was originally introduced into England in the form of the Calabar bean in 1840 by Daniell, a British medical officer. During the last century, physostigmine has been used as a treatment for glaucoma, and in the reversal of atropine-induced coma. More recently, physostigmine has been used effectively as an antidote to several drugs possessing central anticholinergic properties. Web site: http://www.delphion.com/details?pn=US04900748__

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Denatured bovine serum albumin milk products and method therefor Inventor(s): Strand; Frederick T. (Phoenix, AZ) Assignee(s): Advanced Nutrition Concepts, Inc. (Phoenix, AZ) Patent Number: 5,473,050 Date filed: October 12, 1993

Patents 103

Abstract: A method of producing denatured bovine serum albumin (BSA) milk products is disclosed which provides a container for containing the milk products and a source of heating the container for a period of time and within a certain temperature range sufficient for producing the denatured BSA milk products without substantially diminishing either the flavor or the nutritional value of the milk products. It appears that the consumption of denatured BSA milk products, as opposed to consumption of non-denatured BSA milk products, will tend to reduce the likelihood of a person acquiring Insulin Dependent Diabetes Mellitus (IDDM), atherosclerotic vascular disease, myasthenia gravis, multiple sclerosis, pernicious anemia, and other human autoimmune diseases. Excerpt(s): This invention relates generally to milk products and, more specifically, to denatured bovine serum albumin (BSA) milk products and methods therefor which provide unique methods of processing milk products within specific time and temperature ranges in order to denature the BSA found in milk products without substantially diminishing either the flavor or the nutritional content of these milk products. Diabetes mellitus (DM) is one of the most common metabolic diseases. There are two major types of DM, namely insulin-dependent (IDDM) and non-insulindependent (NIDDM). IDDM is also called juvenile, brittle, autoimmune, or type I diabetes. Although IDDM comprises approximately only 10% of all cases of DM, IDDM affects children more often than NIDDM, and IDDM is typically more difficult to manage. There are about 300,000 people in the United States with IDDM and nearly 30,000 new cases are diagnosed each year. Most cases of IDDM result from the destruction of insulin producing pancreatic beta cells by a person's immune system. The primary purpose for producing denatured BSA milk products is to reduce the number of occurrences of IDDM and other autoimmune diseases also possibly triggered by BSA ingestion. There is a reasonably strong correlation between high per capita milk consumption and the occurrence of IDDM. For example, IDDM is rare in Japan but common in Scandinavia. More than 90% of Japanese adults are lactose intolerant (LI) while fewer than 10% of Scandinavian adults have this genetic trait. The LI trait has a marked effect on human behavior. Specifically, individuals who are LI tend to drink less milk than those who do not have this genetic trait. Thus, per capita milk consumption in Japan is approximately 1/10th that of Scandinavia, and this fact suggests why IDDM is less than 1/10th as common among the largely LI Japanese population. Web site: http://www.delphion.com/details?pn=US05473050__ •

Immunoassay for thymopoietin Inventor(s): Goldstein; Gideon (Riverdale, NY) Assignee(s): Sloan Kettering Institute for Cancer Research (New York, NY) Patent Number: 4,124,700 Date filed: June 27, 1977 Abstract: An immunoassay for the polypeptide thymic hormone thymopoietin is described. Determination of thymopoietin levels in biological fluids provides a useful diagnostic test for myasthenia gravis (elevated levels), immune deficiency diseases (reduced levels), (immunologically mediated diseases such as rheumatoid arthritis, systemic lupus erythematosus and allergy (reduced levels), cancer (reduced levels), malnutrition (reduced levels) and infections (reduced levels). The present assay is also useful as a monitor of the effectiveness of therapy in each of the aforementioned types of disease states.


Excerpt(s): Thymopoietin is a polypeptide hormone of the thymus that induces differentiation of prothymocytes to thymocytes and also has secondary effects on neuromuscular transmission. Two forms of bovine thymopoietin, designated thymopoietin I and II have been isolated and shown to be immunologically cross reactive. (Thymopoietin is now used in preference to the original name Thymin). See G. Goldstein, Nature 247, 11 (1974). Although thymopoietin can be detected by bioassay using either its effects on T cell differentiation or neuromuscular transmission, these assays are complex, timeconsuming, and difficult to standardize. Moreover, unlike immunoassay, and particularly radioimmunoassay, bioassays are not readily automated and thus could not be routinely employed by clinical laboratories or other diagnostic facilities to screen large numbers of samples in an economic fashion. The present invention relates to an immunoassay for thymopoietin. A preferred immunoassay can give sensitivities down to about 0.1 ng/ml. of the hormone in biological fluid samples such as plasma or serum. Thus the instant assay can be employed as a diagnostic test for disease states which exhibit either elevated (myasthenia gravis) or reduced (aging, immune deficiency or immunologically mediated diseases, cancer, malnutrition, infections and the like) levels of thymopoietin. The two forms of thymopoietin are indistinguishable in immunoassay procedures. Web site: http://www.delphion.com/details?pn=US04124700__ •

Method for the synthesis of huperzine A and analogs thereof and compounds useful therein Inventor(s): Kozikowski; Alan Paul (Pittsburgh, PA), Xia; Yan (Baltimore, MD) Assignee(s): Mayo Foundation for Medical Education and Research (Rochester, MN) Patent Number: 5,663,344 Date filed: July 22, 1994 Excerpt(s): The present invention relates to a method for the synthesis of certain bridged fused ring pyridines. Such bridged fused ring pyridines can be converted to huperzine A and analogs of huperzine A. The present invention also covers such bridged fused ring pyridines, compounds utilized for the preparation of the bridged fused ring pyridines and analogs of huperzine A. Huperzine A, which is a Lycopodium alkaloid, has been isolated from the plant Huperzia serrata. It has been shown to inhibit the cholinesterase enzyme and, therefore, has been tested for the treatment of diseases of the cholinergic system. For example, Huperzine A is being studied for the treatment of myasthenia gravis, Alzheimer's dementia and for the improvement of senile memory loss. See J. Liu, et al., The Structures of Huperzine A and B Two New Alkaloids Exhibiting Marked Anticholinesterase Activity, Can. J. Chem., 64, 837-839 (1986). R.sub.1.sup.2.dbd.R.sub.3.sup.2; R.sub.1.sup.1.dbd.R.sub.3.sup.1; R.sub.2.sup.3.dbd.R.sub.3.sup.3 and n.sub.1 =n.sub.2. Web site: http://www.delphion.com/details?pn=US05663344__

Patents 105

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Method of causing selective immunosuppression using HL-60 related lectins Inventor(s): Bringman; Tim (Solana Beach, CA), Couraud; Pierre-Olivier (Auffargis, FR), Nedwin; Glenn (Davis, CA), Seilhammer; Jeffrey J. (Milpitas, CA) Assignee(s): Incyte Pharmaceuticals, Inc. (Palo Alto, CA) Patent Number: 5,693,760 Date filed: October 20, 1994 Abstract: Pharmaceutical compositions useful in the treatment of autoimmune conditions include as an active ingredient a soluble lectin having a molecular weight of about 14 kilodaltons or a fragment thereof. The lectin or fragment binds.beta.galactoside-containing moieties independent of the presence or absence of Ca.sup.+2, stimulates hemagglutination of trypsinized rabbit erythrocytes in standard lectin assays wherein the stimulation is inhibited by lactose or thiogalactoside, has an amino acid sequence containing at least one N-glycosylation site and is at least 90% homologous to the amino acid sequence shown in positions 2-135 of FIG. 1 or the relevant portions thereof. The composition is used for treatment of autoimmune conditions such as rheumatoid arthritis, myasthenia gravis, and multiple sclerosis, as well as modulating the immune response in an allergic reactions or to organ or tissue transplant rejection. The inventive composition can be combined with general immunosuppressants. Excerpt(s): The invention relates to the use of carbohydrate-binding proteins as regulators of cell differentiation and immunity. In particular, it concerns a pharmaceutical composition where the active ingredient is a soluble lectin of about 14 kD or a fragment thereof which can be isolated from human HL-60 cells or placenta tissue. Recombinant materials and methods to produce these inventive lectins are also provided. This invention is also directed to methods to treat autoimmune diseases and to prevent transplant rejection. Lectins are defined as proteins which specifically bind carbohydrates of various types. Initial interest was focused on those isolated from plants such as concanavalin A and ricin agglutinin. These lectins, it was found, were useful in protein purification procedures due to the glycosylation state of a number of proteins of interest. Among the soluble lectins, there appear to be a number of varieties with varying molecular weights and/or carbohydrate specificities. Sparrow, C. P., et al., J. Biol. Chem. (1987) 252:7383-7390 describe three classes of soluble lectins from human lung, one of 14 kD, one of 22 kD, and a third of 29 kD. All of these lectins are specific to.beta.-D-galactosides. The carbohydrate specificities of the 14 kD class are for the most part similar, but the larger molecular weight species tend to have different specificities. Other species are also noted as showing more than one soluble.beta.-D-galactosidebinding lectin, including mouse (Roff, C. F., et al., J. Biol. Chem. (1983) 258:10637-10663); rat (Cerra, R. F., et al., J. Biol. Chem. (1985) 260:10474-10477) and chickens (Beyer, E. C., et al., J. Biol. Chem. (1980) 255:4236-4239). Among the various.beta.-D-galactosidespecific soluble lectins, ligand specificity is considerably different, and the approximately 14 kD group appears distinct from the 22 kD and 29 kD representatives described by Sparrow, et al., supra. Recently, however, interest has focused on a group of lactose-extractable lectins which bind specifically to certain.beta.-D-galactoside containing moieties and are found in a wide range of mammalian, invertebrate, avian, and even microbial sources. All of the lectins in this class appear to contain subunits with molecular weights of about 12-18 kD. Furthermore, these lectins can be readily classified by virtue of a simple diagnostic test: their ability to agglutinate trypsin-treated rabbit red blood cells is specifically inhibited by certain.beta.-D-galactose-containing moieties. Thus, although the lectins themselves agglutinate trypsinized rabbit erythrocytes, the agglutination can be inhibited by, for example, lactose,


thiodigalactoside and certain other.beta.-D-galactose containing moieties. Other common characteristics include no requirement for metal ions in effecting agglutination and the required presence of a reducing agent such as a thiol. Web site: http://www.delphion.com/details?pn=US05693760__ •

Method of treating myasthenia gravis and related diseases Inventor(s): Drachman; Daniel B. (Baltimore, MD), Kuncl; Ralph W. (Baltimore, MD) Assignee(s): The Johns Hopkins University (Baltimore, MD) Patent Number: 4,918,060 Date filed: September 4, 1987 Abstract: A method of treating a disorder of receptors involving mediation by endocytosis which comprises administering to a host suffering from said disorder, an effective amount of 3-deazaadenosine or periodate-oxidized adenosine. Excerpt(s): The present invention is concerned with the treatment of diseases of receptors mediated by endocytosis. The invention is particularly concerned with the treatment of myasthenia gravis although the treatment of other generally related diseases involving abnormalities of receptors which are mediated by endocytosis is also contemplated. The work described herein was supported by grants from the National Institute of Health. Myasthenia gravis is a disease characterized by muscle weakness and fatigability, caused by an autoimmune attack by antibody directed against the acetylcholine receptor (AChR). Such attack results in the blockade and loss of AChRs at neuromuscular junctions. Web site: http://www.delphion.com/details?pn=US04918060__

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Methods and polycyclic aromatic compound containing compositions for treating Tcell-mediated diseases Inventor(s): Lavie; Gad (Tenafly, NJ), Meruelo; Daniel (Scarborough, NY) Assignee(s): New York University (New York, NY) Patent Number: 5,514,714 Date filed: March 30, 1993 Abstract: T cell-mediated diseases in mammals are treated using compositions comprising a polycyclic aromatic compound, preferably hypericin or pseudohypericin, and related compounds, including isomers, analogs, derivatives, salts, or ion pairs of hypericin or pseudohypericin. The above composition may be administered in combination with an immunosuppressive agent. Pharmaceutical compositions useful for treating a T cell-mediated disease comprise the above polycyclic aromatic compound, alone or in combination with an immunosuppressive agent. The compositions and methods are useful in treating diseases which include multiple sclerosis, myasthenia gravis, scleroderma, polymyositis, graft-versus-host disease, graft rejection, Graves disease, Addison's disease, autoimmune uveoretinitis, autoimmune thyroiditis, pemphigus vulgaris and rheumatoid arthritis. Psoriasis and systemic lups erythematosus. Also provided are methods for diminishing the expression of CD4 Molecules on the surface of a T lymphocyte, and for inducing multidrug resistance in a

Patents 107

cell, comprising incubating the cell with an effective concentration of a polycyclic aromatic compound. Excerpt(s): This invention pertains to the administration of polycyclic aromatic compounds for the treatment of T cell-mediated diseases in mammals and compositions useful for treating T cell-mediated diseases. T cell-mediated diseases have been characterized by the induction of cytotoxic T-lymphocytes expressing the CD8 antigen on their cell surface and/or helper T cells expressing the CD4 antigen on their cell surface. These diseases, non-limiting examples being graft-versus-host diseaser graft rejection, and autoimmune disorders, such as multiple sclerosis, rheumatoid arthritis, Graves diseases Addison's diseases polymyositis, insulin dependent diabetes, primary biliary cirrhosis, systemic Lupus erythematosus, psoriasis, scleroderma, represent a large number of host immune system disorders. Graft-versus-host disease may occur when cells of the immune system such as stem cells or lymphocytes are transplanted into an allogeneic host, such as one genetically different at the major histocompatibility complex, which encodes cell surface antigens that give rise to strong immunological reactions. Transplants of cells of the immune system are made for treating certain forms of leukemia, aplastic anemia, and various immunodeficiency diseases. In order to prevent rejection of the foreign cells, the host is typically immunosuppressed, as with irradiation and/or immunosuppressive drugs. The transplanted immunocompetent cells recognize the host as foreign and mount an immune response directed against the host. In humans, the clinical manifestations of this graft-versus-host disease include fever, rash, anorexia, nausea, vomiting and watery or bloody diarrhea, weight loss and death. Web site: http://www.delphion.com/details?pn=US05514714__ •

Methods for treating autoimmune diseases with 5C8-specific antibodies Inventor(s): Chess; Leonard (Scarsdale, NY), Lederman; Seth (New York, NY), Yellin; Michael J. (Riverdale, NY) Assignee(s): The Trustees of Columbia University in the City of New York (New York, NY) Patent Number: 6,592,868 Date filed: June 7, 1995 Abstract: This invention provides methods of treating autoimmune diseases, including those selected from the group consisting of rheumatoid arthritis, Myasthenia gravis, systemic lupus erythematosus, Graves' disease, idiopathic thrombocytopenia purpura, hemolytic anemia and diabetes mellitus with 5C8-specific antibodies. Excerpt(s): Throughout this application, various publications are referenced by Arabic numerals within parenthesis. Full citations for these publications may be found at the end of the specification, immediately preceding the claims. The disclosures of these publications are hereby incorporated by reference into this application in order to more full describe the state of the art as one skilled therein as of the date of the invention described and claimed herein. In a contact-dependent process termed "T cell helper function," CD4.sup.+ T lymphocytes direct the activation and differentiation of B lymphocytes and thereby regulate the humoral immune response by modulating the specificity, secretion and isotype-encoded functions of antibody molecules (1-8). The T cell surface molecules that mediate the contact-dependent elements of T cell helper function are not yet fully known (9). The process by which T cells help B cells to


differentiate has been divided into two distinct phases: the inductive and effector phases (10,11). In the inductive phase, resting T cells contact antigen-primed B cells and this association allows clonotypic T cell receptor (TCR)-CD4 complexes to interact with Ia/Ag complexes on B cells (5, 12-19). TCR/CD4 recognition of Ia/Ag results in the formation of stable T-B cognate pairs and bidirectional T and B cell activation (20-26). In the effector phase, activated T cells drive B cell differentiation by secreting lymphokines (27-30) and by contact-dependent stimuli (24,31-38), both of which are required for T cells to drive small, resting B cells to terminally differentiate into Ig secreting cells (31, 39-42). Web site: http://www.delphion.com/details?pn=US06592868__ •

Nornicotine enantiomers for use as a treatment for dopamine related conditions and disease states Inventor(s): Bardo; Michael Thomas (Lexington, KY), Crooks; Peter A. (Lexington, KY), Dwoskin; Linda Phyliss (Lexington, KY) Assignee(s): The University of Kentucky Research Foundation (Lexington, KY) Patent Number: 5,776,957 Date filed: November 15, 1996 Abstract: Optically active nornicotine compounds as a treatment for dopamine-related conditions and disease states. Such disease states include the treatment of myasthenia gravis, Parkinson's disease, Alzheimer's disease, schizophrenia, eating disorders, ulcers, drug addiction and as a substitute for psycho-stimulant self-administration. Excerpt(s): This invention is directed to the use of optically active nornicotine compounds as a treatment for dopamine-related conditions and disease states. Such disease states include the treatment of myasthenia gravis, Parkinson's disease, Alzheimer's disease, shizophrenia, eating disorders, drug addiction and use of nornicotine enantiomers as a substitute for psycho-stimulant self-administration. Many disease states and conditions are associated with nicotinic receptors and dopamine release. These include myasthenia gravis, Parkinson's disease, Alzheimer's disease, shizophrenia, eating disorders and drug addiction to name a few. The behavioral effects of nicotine are attributed to an action on the CNS, since most of the effects are blocked by mecamylamine (Clarke, 1987) and more recently by dihydro-.beta.-erythroidine (DH.beta.E; Damaj et al., 1995). Mecamylamine is a CNS-active, noncompetitive nicotinic antagonist (Loiacono et al., 1993; Peng et al., 1994), and DH.beta.E is a selective, competitive nicotinic receptor antagonist (Alkondon and Albuquerque, 1991; Mulle et al., 1991). Mecamylamine blocks nicotine interoceptive cues in discrimination studies (Stolerman et al., 1984), and mecamylamine pretreatment has been shown to influence cigarette smoking behavior and the subjective effects of nicotine (Stolerman et al., 1973; Rose et al., 1994). Web site: http://www.delphion.com/details?pn=US05776957__

Patents 109

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Phenylcarbamates of (-)-eseroline, (-)-N1-noreseroline and (-)-N1-benzylnoreseroline: selective inhibitors of acetyl and butyrylcholinesterase, pharmaceutical compositions and method of use thereof Inventor(s): Brossi; Arnold (Bethesda, MD), Brzostowska; Malgarzota (Poznan, PL), Greig; Nigel (Silver Spring, MD), Rapoport; S. (Washington, DC) Assignee(s): The United States of America as represented by the Secretary of the (Washington, DC) Patent Number: 5,998,460 Date filed: July 26, 1993 Abstract: The present invention relates to eseroline, N.sup.1 -noreseroline, and N.sup.1 benzylnoreseroline phenyl carbamate analogues which provide highly potent and selective cholinergic agonist and blocking activity and their use as pharmaceutical agents. The invention further relates to improvements in therapeutic methods related to diseases such as glaucoma, myasthenia gravis, alzheimer's disease and to improvements in therapy related to organophosphate poisoning. The invention further provides for selective acetyl-cholinesterase and butyrylcholinesterase agents and a method for inhibiting these esterases. Excerpt(s): The present invention relates to improvements in the treatment of diseases, and more particularly to compounds which exhibit selective inhibition of acetylcholinesterase and butyrylcholinesterase. Physostigmine, also called eserine, and particular derivatives of physostigmine are anti-cholinesterase inhibitors which are well known. Such well known compounds are also useful in the treatment of glaucoma, Myasthenia Gravis, Alzheimer's disease and as antidotes against poisoning with organophosphates. It has been discovered that the natural isomer of physostigmine has blocking properties as well as agonist properties at the neuromuscular AChR. By contrast (+)-physostigmine shows only negligible inhibition of cholinesterase (ChE). See Brossi et al., FEBS Lett., Vol. 201, pages 190-192 (1986). Web site: http://www.delphion.com/details?pn=US05998460__

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PVA or PEG conjugates of peptides for epitope-specific immunosuppression Inventor(s): Ashizawa; Tetsuo (3435 Westheimer Rd., #301, Houston, TX 77027), Atassi; M. Zouhair (11743 Cawdor Way, Houston, TX 77024) Assignee(s): none reported Patent Number: 6,048,529 Date filed: March 29, 1995 Abstract: The invention relates to a procedure for synthesis of well-defined conjugates of peptides to the tolerogenic polymer monomethoxypolyethylene glycol (mPEG) or polyvinyl alcohol (PVA). This method results in the preparation of conjugates in which one molecule of tolerogenic polymer is specifically coupled to one or the other or both of the termini of an otherwise unaltered peptide molecule. A synthetic peptide synthesized using this method and corresponding to a myasthenogenic region of an acetylcholine receptor was conjugated to monomethoxypolyethylene glycol. Injection of animals with the mPEG-conjugate and subsequent immunization with whole receptor suppressed the development of experimental autoimmune myasthenia gravis (EAMG) by


electrophysiological criteria. Specifically-conjugated, tolerogenic peptides are also disclosed for diseases as diverse as ragweed pollen allergy and Grave's disease. Excerpt(s): The invention relates, in one aspect, to a procedure for synthesis of welldefined conjugates of peptides covalently bonded to a tolerogenic polymer such as monomethoxypolyethylene glycol (MPEG) or polyvinyl alcohol (PVA). The first step in said synthesis involves succinylation of free-hydroxyl groups on the tolerogenic polymer by reaction with succinic anhydride. The polymer is then coupled to one or the other terminus, for instance via the carboxyl of a succinyl group to the.alpha.-NH.sub.2, of a peptide. This is achieved while maintaining intact all the side-chain protecting groups on the peptide. The MPEG or PVA-peptide conjugate are cleaved from a synthetic resin and purified. This method results in the preparation of conjugates in which one molecule of tolerogenic polymer is specifically coupled to one or the other or both of the termini of an otherwise unaltered peptide molecule. In order to test the ability of such tolerogenic peptides to suppress antibody responses in an autoimmune disease, a synthetic peptide,.alpha.125-148, corresponding to a myasthenogenic region of Torpedo californica acetylcholine receptor (AChR) was conjugated to monomethoxypolyethylene glycol (MPEG). Injection of mice with the MPEG(.alpha.125-148) conjugate and subsequent immunization with whole Torpedo AChR suppressed the development of experimental autoimmune myasthenia gravis (EAMG) by electrophysiological criteria. In anti-AChR antisera from these animals, the antibody response against the unconjugated peptide.alpha.125-148 was decreased while the antibody responses against whole AChR and other epitopes were not altered. There were no detectable changes in T cell proliferation responses to peptide.alpha.125-148 or to whole AChR in these animals. Prior injections with a "nonsense" peptide mPEG conjugate had no effect on responses to the subsequent immunization with whole Torpedo AChR. The results indicate that the mPEG-(.alpha.125-148) conjugate has epitope-specific tolerogenicity for antibody responses in EAMG, and that the region.alpha.125-148 plays an important pathophysiological role in EAMG. These studies strongly indicate that other epitope-directed tolerogenic conjugates will be useful for future immunotherapies of human myasthenia gravis. Tolerogenic peptides are also disclosed for diseases as diverse as ragweed pollen allergy and Grave's disease. The strategy of specific suppression of the antibody response to a pre-determined epitope using a synthetic mPEG-peptide conjugate will be useful in manipulation and suppression of unwanted immune responses such as autoimmunity and allergy. Web site: http://www.delphion.com/details?pn=US06048529__ •

Synthetic peptides for the treatment of myasthenia gravis Inventor(s): Mozes; Edna (Rehovot, IL), Sela; Michael (Rehovot, IL) Assignee(s): Yeda Research and Development Co. Ltd. (Rehovot, IL) Patent Number: 6,066,621 Date filed: June 7, 1995 Abstract: Peptides having at least nine amino acid residues each including an amino acid sequence which corresponds to position p200-208 or p262-266 of the human acetylcholine receptor.alpha.-subunit, but differing therefrom by one or more amino acid substitutions, are disclosed. These peptides inhibit the proliferative response of human peripheral blood lymphocytes to the myasthenogenic peptides p195-212 and p259-271 and are suitable for treatment of subjects afflicted with myasthenia gravis.

Patents 111

Excerpt(s): The present invention relates to synthetic peptides useful for the treatment of myasthenia gravis (MG) patients, and to pharmaceutical compositions comprising these peptides by themselves, in a combined or polymerized form, or attached to a macromolecular carrier. Autoimmune diseases are characterized by immune responses that are directed against self antigens. These responses are maintained by the persistent activation of self-reactive T lymphocytes. T lymphocytes are specifically activated upon recognition of foreign and/or self antigens as a complex with self Major Histocompatibility Complex (MHC) gene products on the surface of antigen-presenting cells (APC). Myasthenia gravis (MG) is an autoimmune disorder, the symptoms of which are caused by an antibody-mediated autoimmune attack on the acetylcholine receptor (AChR) of the post-synaptic membrane of the neuromuscular junction. This antibody attack results in loss of acetylcholine receptors and jeopardizes normal neuromuscular transmission, leading to episodic muscle weakness, chiefly in muscles innervated by cranial nerves, and to fatigability. Web site: http://www.delphion.com/details?pn=US06066621__ •

Treatment of myasthenia gravis and oral medication therefor Inventor(s): Zappia; Joseph Francis (118 N. Gibson St., Indianapolis, IN 46219) Assignee(s): none reported Patent Number: 4,042,698 Date filed: July 18, 1975 Abstract: A human being having the medical condition known as myasthenia gravis is treated by administering at least an effective amount of strychnine to ameliorate the symptoms of the condition but less than an amount which causes persistent fasciculation of the facial muscles of the human being. The amount of medication given is balanced against the body condition safely and easily by the skilled physician. Daily dosage rates, typically, range from about 1/6000 grain of strychnine, usually as the sulfate, per kilogram of body weight to as high as about 1/300 grain or more for the more severely afflicted, i.e., into the normally fatally toxic range, usually in the form of a 1/60 grain tablet administered at the rate of 1 to 3 tablets every 2 to about 16 waking hours as needed according to the severity of the condition. Mild cases are treated intermittently while severe cases require substantially daily treatment. Vitamin B complex co-administration maximizes the effectiveness of the strychnine and tends to diminish strychnine requirements, although no side reactions of strychnine have been observed. Strychnine requirements may also be reduced by co-administering deanol or neostigmine bromide or the dimethylcarbamate of 3-hydroxy-1-methylpyridinium. Excerpt(s): The invention relates to an improved method for the treatment of the human medical condition known as myasthenia gravis. For the purposes of the following description and the appended claims, myasthenia gravis is defined as a condition typified by a fluctuating condition of easy fatigability of voluntary muscles aggravated by exertion, emotion, menstruation or infection, and relieved, both subjectively and objectively, by rest and anti-cholinesterase drugs. The patient with a so-called mild myasthenia gravis condition generally needs treatment on an intermittent basis as the condition worsens and improves spontaneously in an intermittent manner. The patient with a seriously marked or severe myasthenia gravis condition generally requires treatment on a regular conditioning basis, usually daily. Myasthenia gravis is a problem probably more widespread than heretofore realized for in the past only the more advanced or severe stages of the condition were recognized and labeled as myasthenia


gravis. By ergograms and "Tensilon Tests" rather recently developed we have learned that there can be different degrees of the disease manifesting a variety of symptoms. Moderately servere symptoms can be and often are mistaken for psychological disorders. Not only is the myasthenia gravis patient (myasthenic) not helped by treatment for psychological disorder but suffers more as a result. In the not too severe cases, the condition may be wrongly assessed psychologically as a withdrawal from normal interests and activities. Web site: http://www.delphion.com/details?pn=US04042698__ •

Treatment of myasthenia gravis by cyclic nucleotide phosphodiesterase inhibition Inventor(s): O'Donnell, Jr.; Francis E. (709 The Hamptons La., St. Louis, MO 63017) Assignee(s): none reported Patent Number: 6,413,968 Date filed: June 30, 2000 Abstract: A method of treating myasthenia gravis confined to the eyes iby administering, orally, a therapeutically effective dose the nucleotide (cGMP) phosphodiesterase inhibitor Sildenafil either 100 mg. once a day, or 25 mg. four times a day. The object of this oral therapy being the alleviation of myasthenic complications such as diplopia and ptosis. Excerpt(s): The present invention relates to the treatment of myasthenia gravis and, in particular, to the treatment of the ocular involvement in myasthenia gravis. In strictly ocular myasthenia gravis, for example, there is a male preponderance, relatively lower incidence of anti-acetylcholine receptor antibody and significantly lower serum titers, relatively poor response to anticholinesterase agents alone and a reasonable response to corticosteroids. In myasthenia gravis, as a result of an autoimmune process, the acetylcholine receptors at the myoneural junction are reduced in number. In prior art treatment of myasthenia gravis, an anti-cholinesterase agent is used to increase the effect of acetylcholine at the myoneural junction despite the reduction in receptor density. Studies with parasympathetic enervation of smooth muscle have shown that stimulation by acetylcholine results in a rapid, large increase in cyclic GMP (guanosine 3.sup.1,5.sup.1 --cyclic monophosphate) in the muscle cell. Web site: http://www.delphion.com/details?pn=US06413968__

Patent Applications on Myasthenia Gravis 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 myasthenia gravis:

10

This has been a common practice outside the United States prior to December 2000.

Patents 113

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Antisense oligonucleotide against human acetylcholinesterase (AChE) and uses thereof Inventor(s): Evron, Tama; (Mevasseret Zion, IL), Saidman, Jackiline; (Gush Etzion, IL), Saidman, Shlomo; (Gush Etzion, IL), Soreq, Hermona; (Jerusalem, IL) Correspondence: John P. White; Cooper & Dunham Llp; 1185 Avenue OF The Americas; New York; NY; 10036; US Patent Application Number: 20030216344 Date filed: March 27, 2003 Abstract: The invention relates to an antisense oligonucleotide targeted to the coding region of the human acetylcholinesterase (AChE), which selectively suppresses the AChE-R isoform of the enzyme. The antisense oligonucleotide is intended for use in the treatment and/or prevention of neuromuscular disorders, preferably myasthenia gravis. In addition, it can penetrate the blood-brain barrier (BBB) and destroy AChE-R within central nervous system neurons, while also serving as a carrier to transport molecules across the BBB. Excerpt(s): The present invention relates to a synthetic antisense oligodeoxynucleotide targeted to the common coding domain of human acetylcholinesterase (AChE) mRNA, and to pharmaceutical or medical compositions comprising the same, particularly for the treatment and/or prevention of a progressive neuromuscular disorder. All publications mentioned throughout this application are fully incorporated herein by reference, including all references cited therein. Neuromuscular junctions (NMJ) are highly specialized, morphologically distinct, and well-characterized cholinergic synapses [Hall and Sanes (1993) Cell 72 Suppl., 99-121]. Chronic impairments in NMJ activity induce neuromuscular disorders characterized by progressive deterioration of muscle structure and function. The molecular and cellular mechanisms leading from compromised NMJ activity to muscle wasting have not been elucidated. Web site: http://appft1.uspto.gov/netahtml/PTO/search-bool.html

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Dimeric compounds Inventor(s): Carlier, Paul R.; (Blacksburg, VA), Du, Da-Ming; (Beijing, CN), Han, Yifan; (Hong Kong, HK), Pang, Yuan-Ping; (Rochester, MN) Correspondence: James A. Labarre; Burns, Doane, Swecker & Mathis, L.L.P.; P.O. Box 1404; Alexandria; VA; 22313-1404; US Patent Application Number: 20020156096 Date filed: February 16, 2001 Abstract: The invention relates to dimeric compounds comprising two 5-amino-5,6,7,8tetrahydroquinoline fragments joined together by a divalent linking group, processes for their preparation, intermediates for their preparation, pharmaceutical compositions containing such dimeric compounds and the use of such compounds as cholinesterase inhibitors and in the treatment of neurodegenerative diseases, such as Alzheimer's Disease and myasthenia gravis. Excerpt(s): This invention relates to dimeric compounds comprising two 5-amino5,6,7,8-tetrahydroquinoline fragments joined together by a divalent linking group, processes for their preparation, intermediates for their preparation, pharmaceutical;compositions containing such dimeric compounds and the use of such


compounds as cholinesterase inhibitors and in the treatment of neurodegenerative diseases, such as Alzheimer's Disease and myasthenia gravis. Total syntheses of the racemate and asymmetric syntheses of huperzine A have been reported (see for instance, Xia, Y.; Kozikowski, A. P; J.Am.Chem.Soc. 1989, 111, 4116-4117; Qian, L.; Ji, R.; Tetrahedroni Lett. 1989, 30, 2089-2090; Yamada, F.; Kozikowski, A. P.; Reddy, E. R.; Pang, Y-P.; Miller, J. H.; McKinney, M.; J.Am.Chem.Soc. 1991, 113, 4695-4696; Kaneko, S.; Yoshino, T.; Katoh, T.; Terashima, S.; Tetrahedron 1998, 54, 5471-5484; and He, X. -C.; Wang, B.; Bai, D.; Tetrahedron Lett. 1998, 39, 411-414.However, these syntheses require a minimum of 12 steps. Enormous effort has also been directed towards the development of more easily synthesised analogues which might prove to be more potent than huperzine A. More than 100 such analogues have been disclosed in the scientific and patent literature. For instance, U.S. Pat. No. 5,929,084 discloses huperzine A derivatives in which the hydrogen atom at the 1-position in huperzine A is optionally replaced by a C.sub.1-5 alkyl, pyridoyl or C.sub.1-5 alkoxy-substituted benzoyl group and the amino group at the 5-position in huperzine A is replaced by a group --N(R")YR where Y is a carbonyl group, R" is a hydrogen atom or a C.sub.1-5 alkyl group, or R" and Y together form a group.dbd.CH, and R is a C.sub.1-5 alkyl or an optionally substituted phenyl, benzyl, naphthyl or pyridyl group. U.S. Pat. No. 5,547,960 discloses huperzine A derivatives which are mono- or disubstituted at the 10-position. Substitution at other positions of the huperzine A molecule is also contemplated in U.S. Pat. No. 5,547,960 but no examples of any such compounds are provided. However, to date, the only huperzine A analogues which have shown superior potency relative to the natural product feature the judicious addition of one or two methyl groups at the 10-position. In this respect, the compounds of formula A above in which R is methyl and R' is hydrogen and both R and R' are methyl are 8- and 1.4-fold more potent than huperzine A respectively. However, the syntheses of these compounds are longer than that of the natural product. Web site: http://appft1.uspto.gov/netahtml/PTO/search-bool.html •

Immunodominant acetylcholine receptor alpha subunit peptide: MHC complexes Inventor(s): Arimilli, Subhashini; (Greensboro, NC), Deshpande, Shrikant; (Fremont, CA), Spack, Edward; (Mountain View, CA), Wehner, Nancy; (Fremont, CA) Correspondence: Townsend And Townsend And Crew, Llp; Two Embarcadero Center; Eighth Floor; San Francisco; CA; 94111-3834; US Patent Application Number: 20030144477 Date filed: September 30, 2002 Abstract: The present invention is directed to the treatment of autoimmune diseases, in particular of myasthenia gravis. This invention provides novel autoimmune dominant peptides derived from the acetylcholine receptor, as well as methods for preparing the peptides. The present invention further provides complexes comprising these peptides associated with an appropriate major histocompatibility complex (MHC) molecule and methods for making these complexes. The complexes of the present invention can be used therapeutically or prophylactically for treating myasthenia gravis. Excerpt(s): The present application claims priority to U.S. Ser. No. 60/327,495, filed Oct. 4, 2001, herein incorporated by reference in its entirety. This application is related to published PCT application WO 01/74848, herein incorporated by reference in its entirety. Not applicable.

Patents 115

Web site: http://appft1.uspto.gov/netahtml/PTO/search-bool.html •

METHODS FOR TREATING VASCULAR DEMENTIA Inventor(s): Pratt, Raymond; (Leonia, NJ) Correspondence: Edward D. Grieff, ESQ.; Hale And Dorr Llp; 1455 Pennsylvania Avenue, NW; Washington; DC; 20004; US Patent Application Number: 20020040038 Date filed: September 4, 2001 Abstract: The invention describes novel methods for treating and preventing dementia caused by vascular diseases; dementia associated with Parkinson's disease; Lewy Body dementia; AIDS dementia; mild cognitive impairments; age-associated memory impairments; cognitive impairments and/or dementia associated with neurologic and/or psychiatric conditions, including epilepsy, brain tumors, brain lesions, multiple sclerosis, Down's syndrome, Rett's syndrome, progressive supranuclear palsy, frontal lobe syndrome, and schizophrenia and related psychiatric disorders; cognitive impairments caused by traumatic brain injury, post coronary artery by-pass graft surgery, electroconvulsive shock therapy, and chemotherapy, administering a therapeutically effective amount of at least one of the cholinesterase inhibitor compounds described herein. The invention also describes novel methods for treating and preventing delirium, Tourette's syndrome, myasthenia gravis, attention deficit hyperactivity disorder, autism, dyslexia, mania, depression, apathy, and myopathy associated with diabetes by administering a therapeutically effective amount of at least one of the cholinesterase inhibitor compounds described herein. The invention also describes novel methods for delaying the onset of Alzheimer's disease, for enhancing cognitive functions, for treating and preventing sleep apnea, for alleviating tobacco withdrawal syndrome, and for treating the dysfunctions of Huntington's Disease by administering a therapeutically effective amount of at least one of the cholinesterase inhibitor compounds described herein. A preferred cholinesterase inhibitor for use in the methods of the invention is donepezil hydrochloride or ARICEPT.RTM. Excerpt(s): This application claims priority to PCT Application No. PCT/US01/07027 filed Mar. 5, 2001, which claims priority to U.S. Provisional Application No. 60/259,226 filed Jan. 3, 2001, U.S. Provisional Application No. 60/220,783 filed Jul. 25, 2000, U.S. Provisional Application No. 60/197,610 filed Apr. 18, 2000, and U.S. Provisional Application No. 60/186,744 filed Mar. 3, 2000. Novel cholinesterase inhibitors are described in U.S. Pat. No. 4,895,841 and WO 98/39000, the disclosures of which are incorporated by reference herein in their entirety. The cholinesterase inhibitors described in U.S. Pat. No. 4,895,841 include donepezil hydrochloride or ARICEPT.RTM., which has proven to be a highly successful drug for the treatment of Alzheimer's disease. Web site: http://appft1.uspto.gov/netahtml/PTO/search-bool.html


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PICORNAVIRUSES, VACCINES AND DIAGNOSTIC KITS Inventor(s): NIKLASSON, BO; (STOCKHOLM, SE) Correspondence: James F. Haley, JR., ESQ.; C/o Fish & Neave; 1251 Avenue OF The Americas - 50th Floor; New York; NY; 10020; US Patent Application Number: 20030044960 Date filed: March 11, 1999 Abstract: A new group of picornaviruses is disclosed. The picornaviruses of the invention comprise in the non-coding region of their viral genome a nucleotide sequence which corresponds to cDNA sequence (I) or homologous sequences having at least 75% homology to the SEQ ID NO:1, and they cause mammalian disease. Further aspects of the invention comprise a protein corresponding to a protein of the picornaviruses, antiserum or antibody directed against a protein of the picornaviruses, antigen comprising a protein of the picornaviruses, diagnostic kits, vaccines, use of the picornaviruses in medicaments, particularly for the treatment or prevention of Myocarditis, Cardiomyopathia, Guillain Barr Syndrome, and Diabetes Mellitus, Multiple Sclerosis, Chronic Fatique Syndrome, Myasthenia Gravis, Amyothrophic Lateral Sclerosis, Dermatomyositis, Polymyositis, Spontaneous Abortion, and Sudden Infant Death Syndrome, and methods of treatment of diseases caused by the picornaviruses. 1 SEQ ID NO: 1 (Ljungan 87-012) AGTCTAGTCT TATCTTGTAT GTGTCCTGCA CTGAACTTGT 50 TTCTGTCTCT GGAGTGCTCT ACACTTCAGT AGGGGCTGTA CCCGGGCGGT 100 CCCACTCTTC ACAGGAATCT GCACAGGTGG CTTTCACCTC TGGACAGTGC 150 (I) ATTCCACACC CGCTCCACGG TAGAAGATGA TGTGTGTCTT TGCTTGTGAA 200 AAGCTTGTGA AAATCGTGTG TAGGCGTAGC GGCTACTTGA GTGCCAGCGG 250 ATTACCCCTA GTGGTAACAC TAGC Excerpt(s): The present invention relates to new picornaviruses, proteins expressed by the viruses, antisera and antibodies directed against said viruses, antigens comprising structural proteins of said viruses, diagnostic kits, vaccines, use of said viruses, antisera or antibodies and antigens in medicaments, and methods of treating or preventing diseases caused by said viruses, such as Myocarditis, Cardiomyopathia, Guillain Barr Syndrome, and Diabetes Mellitus, Multiple Sclerosis, Chronic Fatigue Syndrome, Myasthenia Gravis, Amyothrophic Lateral Sclerosis, Dermatomyositis, Polymyositis, Spontaneous Abortion, and Sudden Infant Death Syndrome. Recently, a sudden death syndrome among Swedish orienteers has been observed. Of approximately 200 elite orienteers six died in myocarditis during 1989-1992 (1). Orienteering, aiming to find the fastest/shortest way between several checkpoints and often in forested areas, is exceptional with respect to environmental exposure. Thus it has been speculated, that the sudden deaths syndrome among orienteers is caused by a vector borne (rodent or arthropod) infectious agent. It has now been shown in an epidemiological study that the incidence of deaths in myocarditis in northern Sweden tracked the 3-4 year population fluctuations (cycles) of bank voles (Clethrionomys glareolus) with one year time lag. Previously, it has been shown that cardioviruses, with rodents as their natural reservoir, can cause Guillain Barr Syndrome (GBS) in man, Diabetes Mellitus (DM) in mice and myocarditis in several species including non-human primates. Web site: http://appft1.uspto.gov/netahtml/PTO/search-bool.html

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Recombinant fragments of the human acetylcholine receptor and their use for treatment of myasthenia gravis Inventor(s): Barchan, Dora; (Rishon LeZion, IL), Fuchs, Sara; (Rehovot, IL), Souroujon, Miriam C.; (Rehovot, IL) Correspondence: Browdy And Neimark, P.L.L.C.; 624 Ninth Street, NW; Suite 300; Washington; DC; 20001-5303; US Patent Application Number: 20020081652 Date filed: March 29, 2001 Abstract: Polypeptides capable of modulating the autoimmune response of an individual to human acetylcholine receptor (hAChR), more particularly polypeptides corresponding entirely or partially to the extracellular domain of hAChR.alpha.-subunit, are useful in the diagnosis and treatment of myasthenia gravis. Preferred polypeptides are polypeptides corresponding to amino acid residues 1-121 or 122-210 of the hAChR.alpha.-subunit sequence, and polypeptides corresponding to amino acid residues 1-121, 1-210 or 1-205 of the hAChR.alpha.-subunit sequence in which is inserted, between amino acid residues 58 and 59, a sequence of 25 amino acid residues encoded by the p3A exon of the hAChR.alpha.-subunit gene, and fragments, analogs, fused, soluble and denatured forms thereof. DNA molecules encoding said polypeptides are also provided. Excerpt(s): This application is a continuation-in-part of application Ser. No. 09/423,398, filed Nov. 8, 1999, as a 371 national stage application of PCT/IL98/00211, filed May 6, 1998, the entire contents of which are incorporated herein by reference. The present invention relates to polypeptides capable of modulating the autoimmune response to acetylcholine receptor, and more particularly to polypeptides corresponding entirely or partially to the extracellular domain of human acetylcholine receptor.alpha.-subunit, which polypeptides are useful in the diagnosis and treatment of myasthenia gravis, and to DNA molecules encoding said polypeptides. ABBREVIATIONS: AChR--acetylcholine receptor;.alpha.-BTX --.alpha.-bungarotoxin; EAMG--experimental autoimmune myasthenia gravis; GST--glutathione S-transferase; hAChR--human acetylcholine receptor; MG--myasthenia gravis; LNC--lymph node cells; MIR--main immunogenic region. Web site: http://appft1.uspto.gov/netahtml/PTO/search-bool.html

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Tricyclic sulfonamides metalloproteinases

and

their

derivatives

as

inhibitors

of

matrix

Inventor(s): O'Brien, Patrick Michael; (Stockbridge, MI), Picard, Joseph Armand; (canton, MI), Sliskovic, Drago Robert; (Saline, MI) Correspondence: Attention OF Ronald A. Daignault; Merchant & Gould P.C.; P.O. Box 2903; Minneapolis; MN; 55402-0903; US Patent Application Number: 20020169164 Date filed: March 27, 2002 Abstract: Tricyclic sulfonamide compounds and derivatives are described as well as methods for the preparation and pharmaceutical compositions of same, which are useful as inhibitors of matrix metalloproteinases, particularly gelatinase A, collagenase-3, and stromelysin-1 and for the treatment of multiple sclerosis, atherosclerotic plaque rupture,


aortic aneurysm, heart failure, left ventricular dilation, restenosis, periodontal disease, or other autoimmune or inflammatory disorders dependent upon tissue invasion by leukocytes or other activated migrating cells, acute and chronic neurodegenerative disorders including stroke, head trauma, spinal cord injury, Alzheimer's disease, amyotrophic lateral sclerosis, cerebral amyloid angiopathy, AIDS, Parkinson's disease, Huntington's disease, prion diseases, myasthenia gravis, and Duchenne's muscular dystrophy. Excerpt(s): The present invention relates to novel tricyclic sulfonamide compounds and their derivatives useful as pharmaceutical agents, to methods for their production, to pharmaceutical compositions which include these compounds and a pharmaceutically acceptable carrier, and to pharmaceutical methods of treatment. The novel compounds of the present invention are inhibitors of matrix metalloproteinases, e.g., gelatinase A (MMP-2), collagenase-3 (MMP-13), and stromelysin-1 (MMP-3): More particularly, the novel compounds of the present invention are useful in the treatment of atherosclerotic plaque rupture, aortic aneurism, heart failure, left ventricular dilation, restenosis, periodontal disease, corneal ulceration, treatment of burns, decubital ulcers, wound repair, cancer, inflammation, pain, arthritis, osteoporosis, multiple sclerosis, renal disease, and other autoimmune or inflammatory disorders dependent on the tissue invasion of leukocytes or other activated migrating cells. Additionally, the compounds of the present invention are useful in the treatment of acute and chronic neurodegenerative disorders including stroke, head trauma, spinal cord injury, Alzheimer's disease, amyotrophic lateral sclerosis, cerebral amyloid angiopathy, AIDS, Parkinson's disease, Huntington's disease, prion diseases, myasthenia gravis, and Duchenne's muscular dystrophy. Gelatinase A and stromelysin-1 are members of the matrix metalloproteinase (MMP) family (Woessner J. F., FASEB J., 1991;5:2145-2154). Other members include fibroblast collagenase, neutrophil collagenase, gelatinase B (92 kDa gelatinase), stromelysin-2, stromelysin-3, matrilysin, collagenase 3 (Freije J. M., Diez-Itza I., Balbin M., Sanchez L. M., Blasco R., Tolivia J., and Lopez-Otin C., J. Biol. Chem., 1994;269:16766-16773), and the newly discovered membrane-associated matrix metalloproteinases (Sato H., Takino T., Okada Y., Cao J., Shinagawa A., Yamamoto E., and Seiki M., Nature, 1994;370:61-65). The catalytic zinc in matrix metalloproteinases is a focal point for inhibitor design. The modification of substrates by introducing chelating groups has generated potent inhibitors such as peptide hydroxymates and thiolcontaining peptides. Peptide hydroxamates and the natural endogenous inhibitors of MMPs (TIMPs) have been used successfully to treat animal models of cancer and inflammation. 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 myasthenia gravis, 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 “myasthenia gravis” (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 myasthenia gravis.

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You can also use this procedure to view pending patent applications concerning myasthenia gravis. 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 MYASTHENIA GRAVIS Overview This chapter provides bibliographic book references relating to myasthenia gravis. In addition to online booksellers such as www.amazon.com and www.bn.com, excellent sources for book titles on myasthenia gravis 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: Federal Agencies The Combined Health Information Database collects various book abstracts from a variety of healthcare institutions and federal agencies. To access these summaries, go directly to the following hyperlink: http://chid.nih.gov/detail/detail.html. You will need to use the “Detailed Search” option. To find book summaries, 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. For the format option, select “Monograph/Book.” Now type “myasthenia gravis” (or synonyms) into the “For these words:” box. You should check back periodically with this database which is updated every three months. The following is a typical result when searching for books on myasthenia gravis: •

Effects of Drugs on Communication Disorders. 2nd ed Source: San Diego, CA: Singular Publishing Group. 1999. 238 p. Contact: Available from Singular Publishing Group, Inc. 401 West 'A' Street, Suite 325, San Diego, CA 92101-7904. (800) 347-7707. Fax (800) 774-8398. E-mail: [email protected]. Website: www.singpub.com. PRICE: $49.95 plus shipping and handling. ISBN: 1565939964. Summary: This handbook gives communication specialists information about prescription drugs and their use with patients who suffer neurogenic or psychogenic communication disorders. The book was designed for communication specialists who work in medical centers, rehabilitation clinics, private practice, public schools, or any setting in which drug therapy may influence a client's communication. Chapter 1 is a discussion of why and how drugs work, the scientific basis of neuropharmacology.


Chapter 2 contains general information about drug related issues, including how drugs are administered and arrive at their destination in the body, the procedures for drug approval by the Food and Drug Administration (FDA), the influence of age on drug effectiveness, how to evaluate the effectiveness of a drug, and a discussion of dietary supplements and naturally occurring remedies. The authors next discuss the underlying neurologic and psychiatric diseases and conditions most likely to be encountered by speech language pathologists, along with the medicines currently and most commonly used to treat the disorders. Disorders covered include Parkinson disease, myasthenia gravis, amyotrophic lateral sclerosis (ALS), multiple sclerosis, Wilson's disease, cerebral palsy, Huntington's disease, Tourette's syndrome, stroke, epilepsy, neoplasm (brain tumors), dementia, Alzheimer disease, traumatic brain injury (TBI), depression, mania, bipolar disorder, generalized anxiety disorder, schizophrenia, autism, attention deficit hyperactivity disorder (ADHD), stuttering, spasmodic dysphonia, and dysphagia (swallowing disorders). The handbook concludes with a glossary of terms related to medical conditions and management, an appendix of abbreviations and definitions of terms associated with medical management, an appendix of drugs that affect the ear and hearing, and a subject index.

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 “myasthenia gravis” at online booksellers’ Web sites, you may discover non-medical books that use the generic term “myasthenia gravis” (or a synonym) in their titles. The following is indicative of the results you might find when searching for “myasthenia gravis” (sorted alphabetically by title; follow the hyperlink to view more details at Amazon.com): •

Attacking Myasthenia Gravis by Ronald E. Henderson, Dr. Ronald E. Henderson; ISBN: 1588381145; http://www.amazon.com/exec/obidos/ASIN/1588381145/icongroupinterna

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Handbook of Myasthenia Gravis and Myasthenic Syndromes by Robert P. Lisak (Editor) (1994); ISBN: 0824788257; http://www.amazon.com/exec/obidos/ASIN/0824788257/icongroupinterna

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Living With Myasthenia Gravis: A Bright New Tomorrow by Jean Welch Kempton; ISBN: 0398023298; http://www.amazon.com/exec/obidos/ASIN/0398023298/icongroupinterna

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Myasthenia Gravis by A. Szobor (2002); ISBN: 9630553120; http://www.amazon.com/exec/obidos/ASIN/9630553120/icongroupinterna

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Myasthenia Gravis by E. X. Albuquerque (Editor) (1983); ISBN: 0412163101; http://www.amazon.com/exec/obidos/ASIN/0412163101/icongroupinterna

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Myasthenia Gravis by Robert Lisak; ISBN: 0721657869; http://www.amazon.com/exec/obidos/ASIN/0721657869/icongroupinterna

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Myasthenia gravis by Raymond Greene; ISBN: 0433126019; http://www.amazon.com/exec/obidos/ASIN/0433126019/icongroupinterna

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Myasthenia Gravis (Clinical Neurology and Neurosurgery Monographs, Vol 5) by Hans J. G. H. Oosterhuis (Editor); ISBN: 0443025800; http://www.amazon.com/exec/obidos/ASIN/0443025800/icongroupinterna

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Myasthenia gravis (SuDoc HE 20.3502:M 99/2/999) by U.S. Dept of Health and Human Services; ISBN: B000111NT0; http://www.amazon.com/exec/obidos/ASIN/B000111NT0/icongroupinterna

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Myasthenia gravis : disease mechanism and immunointervention; ISBN: 8173192944; http://www.amazon.com/exec/obidos/ASIN/8173192944/icongroupinterna

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Myasthenia Gravis and Its Experimental Model: The Immunobiology of an Autoimmune Disease (Molecular Biology Intelligence Unit) by B.M. Conti-Fine, et al; ISBN: 3540614176; http://www.amazon.com/exec/obidos/ASIN/3540614176/icongroupinterna

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Myasthenia Gravis and Myasthenic Syndromes (Contemporary Neurology Series, 56) by Andrew Engel (Editor); ISBN: 0195129709; http://www.amazon.com/exec/obidos/ASIN/0195129709/icongroupinterna

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Myasthenia Gravis and Related Diseases: Disorders of the Neuromuscular Junction (Annals of the New York Academy of Sciences, V. 841) by David P. Richman (Editor), et al (1998); ISBN: 1573311197; http://www.amazon.com/exec/obidos/ASIN/1573311197/icongroupinterna

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Myasthenia Gravis and Related Disorders by Henry J. Kaminski (Editor) (2002); ISBN: 1588290581; http://www.amazon.com/exec/obidos/ASIN/1588290581/icongroupinterna

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Myasthenia Gravis and Related Disorders: Biochemical Basis for Disease of the Neuromuscular Junction (Annals of the New York Academy of Sciences, Vol 998) by Mark A. Agius (Editor) (2003); ISBN: 1573313963; http://www.amazon.com/exec/obidos/ASIN/1573313963/icongroupinterna

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Myasthenia Gravis and Related Disorders: Experimental and Clinical Aspects (Annals of the New York Academy of Sciences, Vol 681) by David P. Richman, Robert L. Ruff, Vanda A. Lennon Audrey S. Penn (1993); ISBN: 0897667565; http://www.amazon.com/exec/obidos/ASIN/0897667565/icongroupinterna

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Myasthenia Gravis and Related Disorders: Experimental and Clinical Aspects (Annals of the New York Academy of Sciences, Vol 681) by Audrey S. Penn, et al (1993); ISBN: 0897667557; http://www.amazon.com/exec/obidos/ASIN/0897667557/icongroupinterna

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Myasthenia Gravis: An Illustrated History by John C. Keesey, et al; ISBN: 1929170041; http://www.amazon.com/exec/obidos/ASIN/1929170041/icongroupinterna

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Myasthenia Gravis: Biology and Treatment (Annals of the New York Academy of Sciences, Vol 505) by Daniel E. Drachman (Editor), Daniel B. Drachman (1988); ISBN: 0897664051; http://www.amazon.com/exec/obidos/ASIN/0897664051/icongroupinterna

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Myasthenia Gravis: Disease Mechanism and Immunointervention by Premkumar Christadoss (Editor); ISBN: 0792362780; http://www.amazon.com/exec/obidos/ASIN/0792362780/icongroupinterna

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Myasthenia Gravis: Pathogenesis and Treatment: Proceedings by International Symposium on Myasthenia Gravis: Pathogenesis and Treatme, Eijiro Satoyoshi; ISBN:


0860082962; http://www.amazon.com/exec/obidos/ASIN/0860082962/icongroupinterna •

Myasthenia Gravis: Pathophysiology and Management (Annals of the New York Academy of Sciences) by David Grob (Editor); ISBN: 0897661435; http://www.amazon.com/exec/obidos/ASIN/0897661435/icongroupinterna

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Myasthenia Gravis: The Immunobiology of an Autoimmune Disease by Bianca M., M.D. Conti-Fine (Editor); ISBN: 1570594066; http://www.amazon.com/exec/obidos/ASIN/1570594066/icongroupinterna

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Plasmapheresis and the immunobiology of myasthenia gravis : proceedings of a symposium; ISBN: 0892894040; http://www.amazon.com/exec/obidos/ASIN/0892894040/icongroupinterna

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The Biochemistry of myasthenia gravis and muscular dystrophy; ISBN: 0124596509; http://www.amazon.com/exec/obidos/ASIN/0124596509/icongroupinterna

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The Official Patient's Sourcebook on Myasthenia Gravis: A Revised and Updated Directory for the Internet Age by Icon Health Publications (2002); ISBN: 0597830762; http://www.amazon.com/exec/obidos/ASIN/0597830762/icongroupinterna

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Thymus Manganese and Myasthenia Gravis by Emanuel Josephson (1958); ISBN: 0686292936; http://www.amazon.com/exec/obidos/ASIN/0686292936/icongroupinterna

The National Library of Medicine Book Index The National Library of Medicine at the National Institutes of Health has a massive database of books published on healthcare and biomedicine. Go to the following Internet site, http://locatorplus.gov/, and then select “Search LOCATORplus.” Once you are in the search area, simply type “myasthenia gravis” (or synonyms) into the search box, and select “books only.” From there, results can be sorted by publication date, author, or relevance. The following was recently catalogued by the National Library of Medicine:11 •

Biologic assays in myasthenia gravis for any agents causing a neuromuscular block. Author: Bergh, Nils P.; Year: 1961; [Lund, Berling, 1953]

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Corticosteroids and neuromuscular transmission: an experimental approach to the treatment of myasthenia gravis with corticosteroids Author: Wolters, E. Ch.; Year: 1977; Amsterdam: P.E.T., 1976

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Genetic studies in myasthenia gravis: heredity and associations with the HLA system and autoimmune diseases Author: Pirskanen, Ritva.; Year: 1978; Helsinki: [s.n.], 1977; ISBN: 9519913688

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Living with myasthenia gravis; a bright new tomorrow. Author: Kempton, Jean Welch.; Year: 1971; Springfield, Ill., Thomas [c1972]

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In addition to LOCATORPlus, in collaboration with authors and publishers, the National Center for Biotechnology Information (NCBI) is currently adapting biomedical books for the Web. The books may be accessed in two ways: (1) by searching directly using any search term or phrase (in the same way as the bibliographic database PubMed), or (2) by following the links to PubMed abstracts. Each PubMed abstract has a "Books" button that displays a facsimile of the abstract in which some phrases are hypertext links. These phrases are also found in the books available at NCBI. Click on hyperlinked results in the list of books in which the phrase is found. Currently, the majority of the links are between the books and PubMed. In the future, more links will be created between the books and other types of information, such as gene and protein sequences and macromolecular structures. See http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=Books.

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Myasthenia gravis Author: Gilroy, John,; Year: 1976; Detroit: Myasthenia Gravis Assn. of Detroit, c1976

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Myasthenia gravis and exophthalmic goiter, being a study of certain possible interrelationships between the two. Author: McCorkle, James Kenneth,; Year: 1966; [Minneapolis] 1952

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Myasthenia gravis. Author: Greene, Raymond.; Year: 1970; Philadelphia, Lippincott [1969]

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Myasthenia gravis; a clinical study with special reference to prevalence and prognosis. Author: Mathisen, Ardis Storm.; Year: 1968; Oslo, Aschehoug, 1961

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The reaction of patients with myasthenia gravis to different agents causing a neuromuscular block. Author: Bergh, Nils P.; Year: 1953; [Lund, Berling, 1953]

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The thymus, myasthenia gravis and manganese, incorporating Myasthenia gravis, manganese & thf [sic] thymus [a paper read before the Essex County Ophthalmological Society, June 24, 1939]. Author: Josephson, Emanuel Mann,; Year: 1955; New York, Chedney Press, c1961

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Thymectomy for myasthenia gravis; a record of experiences at the Massachusetts General Hospital, by Henry R. Viets and Robert S. Schwab. Author: Viets, Henry R. (Henry Rouse),; Year: 1952; Springfield, Ill., Thomas [c1960]

Chapters on Myasthenia Gravis In order to find chapters that specifically relate to myasthenia gravis, an excellent source of abstracts is the Combined Health Information Database. You will need to limit your search to book chapters and myasthenia gravis 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 “myasthenia gravis” (or synonyms) into the “For these words:” box. The following is a typical result when searching for book chapters on myasthenia gravis: •

Neurological Disorders Source: in Scully, C. and Cawson, R.A. Medical Problems in Dentistry. 4th ed. Woburn, MA: Butterworth-Heinemann. 1998. p. 336-373. Contact: Available from Butterworth-Heinemann. 225 Wildwood Avenue, Woburn, MA 01801-2041. (800) 366-2665 or (781) 904-2500. Fax (800) 446-6520 or (781) 933-6333. E-mail: [email protected]. Website: www.bh.com. PRICE: $110.00. ISBN: 0723610568. Summary: Dental staff should be able to recognize abnormalities involving the cranial nerves, especially the trigeminal, facial, glossopharyngeal, vagal and hypoglossal nerves. This chapter on neurologic disorders is from a text that covers the general medical and surgical conditions relevant to the oral health care sciences. Topics include congenital neurological disorders, including cerebral palsy (CP), neural tube defects (spina bifida), syringomyelia, Huntington's chorea, and Friedreich's ataxia; acquired neurological disorders, including the examination and lesions of the cranial nerves, facial sensory loss (facial pain is covered in a separate chapter), facial paralysis, Bell's palsy, trigeminal motor neuropathy, abnormal facial movements (dystonias, dyskinesias, facial tics, Tourette syndrome), multiple cranial nerve palsies, blindness and visual impairment, deafness and hearing impairment, Meniere's disease, autonomic


dysfunction, epilepsy, syncope (fainting), raised intracranial pressure, hypoxic encephalopathy, infections of the nervous system (including HIV and syphilis), cerebrovascular accidents (stroke), Parkinson's disease, multiple sclerosis, Guillain-Barre syndrome (infective or idiopathic polyneuritis), motor neurone disease, mercury intoxication, tumors of the central nervous system (CNS), myasthenia gravis, patients with respiratory paralysis, and peripheral neuropathies. For each condition, the authors discuss general aspects, diagnosis and management issues, dental aspects, and patient care strategies. The chapter includes a summary of the points covered. 1 appendix. 4 figures. 15 tables. 52 references. •

Dysphagia Source: in Edmundowicz, S.A., ed. 20 Common Problems in Gastroenterology. New York, NY: McGraw-Hill, Inc. 2002. p. 33-47. Contact: Available from McGraw-Hill, Inc. 1221 Avenue of the Americas, New York, NY 10020. (612) 832-7869. Website: www.bookstore.mcgraw-hill.com. PRICE: $45.00;plus shipping and handling. ISBN: 0070220557. Summary: Dysphagia is defined as difficulty swallowing, most often described by patients as 'the food gets stuck.' Dysphagia generally is not painful (painful swallowing is termed odynophagia). Symptoms of dysphagia always require a diagnostic evaluation to determine the etiology. This chapter on dysphagia is from a book that focuses on the most common gastroenterological problems encountered in a primary practice setting. The chapter is organized to support rapid access to the information necessary to evaluate and treat most patients with this problems. Topics include definitions and background; principal diagnoses, which can include cerebrovascular accident (stroke), amyotrophic lateral sclerosis (ALS), myasthenia gravis, Parkinson disease, myopathy (muscle weakness), incomplete relaxation of the upper esophageal sphincter, esophageal cancer, peptic stricture, Schatzki ring, achalasia, diffuse esophageal spasm, and aperistalsis of the esophageal body; key points of the patient history; the physical examination; ancillary tests, including videofluoroscopy, barium swallow, endoscopy, and esophageal manometry; treatment options; patient education, including dietary modification and swallowing therapy; common errors in diagnosis and treatment; controversies, including the use of Botox for esophageal motility disorders; and emerging concepts. The chapter includes a chapter outline for quick reference, the text itself, a diagnostic and treatment algorithm, and selected references. 1 figure. 1 table. 15 references.

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Rheumatic Complications of Drugs and Toxins Source: in Maddison, P.J.; et al., Eds. Oxford Textbook of Rheumatology. Volume 2. New York, NY: Oxford University Press, Inc. 1993. p. 1089-1095. Contact: Available from Oxford University Press, Inc., New York, NY. Summary: This chapter for health professionals examines the rheumatological complications of adverse drug reactions and toxins. The clinical features and pathogenesis of drug-induced lupus are discussed. The antinuclear profile in druginduced lupus is described. The risk factors for drug- induced lupus are presented. The features of drug-induced myositis, myasthenia gravis, and scleroderma are highlighted. Chemicals inducing scleroderma-like disease are discussed, including silicone implants, vinyl chloride, rape-seed oil, and contaminated tryptophan supplements. Syndromes associated with food allergy are identified. Drugs and toxins causing gout, bone pain, and rheumatological effects are highlighted. The toxic effects of various antirheumatic

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drugs are described, focusing on analgesics; nonsteroidal anti-inflammatory drugs; disease-modifying, second-line therapy; and corticosteroids. 39 references and 5 tables. •

Evaluation for Dysphagia in Neurogenic Disorders Source: in Leonard, R.; Kendall, K. Dysphagia Assessment and Treatment Planning: A Team Approach. San Diego, CA: Singular Publishing Group, Inc. 1997. p. 29-39. Contact: Available from Singular Publishing Group, Inc. 401 West 'A' Street, Suite 325, San Diego, CA 92101-7904. (800) 521-8545 or (619) 238-6777. Fax (800) 774-8398 or (619) 238-6789. E-mail: [email protected]. Website: www.singpub.com. PRICE: $56.95 plus shipping and handling. ISBN: 156593749X. Summary: This chapter is from a textbook that focuses on the principles of assessment and treatment planning for patients with dysphagia (swallowing dysfunction). The chapter reviews specific swallowing problems associated with the major categories of neurogenic disorders. The author discusses concerns related to diagnostic strategies, and the timing of these strategies, in patients experiencing central nervous system or neuromuscular diseases. The author focuses on diagnostic strategies that provide both qualitative and quantitative information regarding dysphagia in neurogenic patient populations. Bedside and clinical evaluations and dynamic radiographic studies of swallow function represent major components of this diagnostic protocol. The author discusses dysphagia and each of the following neurogenic disorders: stroke, brain injury, cerebral palsy, Parkinson's disease, multiple sclerosis, polymyositis and dermatomyositis, myasthenia gravis, muscular dystrophies, amyotrophic lateral sclerosis (ALS), congenital spinal muscular atrophy, and postpolio syndrome. The author reiterates that dysphagia is a significant clinical problem requiring evaluation and treatment in many individuals with neuromuscular and neurologic degenerative diseases. A thorough clinical examination and appropriate diagnostic imaging studies are necessary to develop an appropriate treatment regimen. 23 references.

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How Vocal Abilities Can Be Limited By Diseases and Disorders of the Central Nervous and Muskuloskeletal Systems Source: in Thurman, L. and Welch, G., eds. Bodymind and Voice: Foundations of Voice Education, Volumes 1-3. 2nd ed. Collegeville, MN: VoiceCare Network. 2000. p. 573-581. Contact: Available from National Center for Voice and Speech (NCVS). Book Sales, 334 Speech and Hearing Center, University of Iowa, Iowa City, IA 52242. Website: www.ncvs.org. PRICE: $75.00 plus shipping and handling. ISBN: 0874141230. Summary: This chapter on diseases and disorders of the central nervous and musculoskeletal system is from a multi-volume text that brings a biopsychosocial approach to the study of the voice. The authors use the phrase 'bodyminds' to describe the interrelationship of perception, memory, learning, behavior, and health, as they combine to affect all environmental interactions, adaptations, and learning. The books are written for teachers, voice professionals, people who use their voices on an avocational basis, and interested members of the general public. This chapter emphasizes the more common neural conditions that affect speaking and singing. Disorders of the nervous system are classified a somatosensory, cognitive, motor, or a combination of the three. The somatic sense processes conscious feedback for control of phonation and reflex feedback control of phonation that is outside conscious awareness. The motor part of the nervous system controls all bodily movements, including the subtle movements of the intrinsic laryngeal, pharyngeal, and tongue muscles. Topics include somatosensory disorders of voice and speech, disorders of cognition in language


and music, motor disorders of voice and speech (conditions of increased or inappropriate movement and those of decreased or absent movement), disorders of the musculoskeletal system (temporomandibular joint disorders, laryngeal tension fatigue syndrome, underconditioned laryngeal muscles and vocal fold tissues), aphasia, spasmodic dysphonia, Parkinson disease, dysarthria, myasthenia gravis, multiple sclerosis, amyotrophic lateral sclerosis (ALS), arthritis, and arytenoid cartilage dislocation. 72 references. •

Speech and Voice Specific Neurologic Disorders Source: in Vogel, D.; Carter, J.E.; Carter, P.B. Effects of Drugs on Communication Disorders. 2nd ed. San Diego, CA: Singular Publishing Group, Inc. 1999. p. 39-101. Contact: Available from Singular Publishing Group, Inc. 401 West 'A' Street, Suite 325, San Diego, CA 92101-7904. (800) 347-7707. Fax (800) 774-8398. E-mail: [email protected]. Website: www.singpub.com. PRICE: $49.95 plus shipping and handling. ISBN: 1565939964. Summary: This chapter on speech and voice specific neurologic disorders is from a handbook that gives communication specialists information about prescription drugs and their use with patients who suffer neurogenic or psychogenic communication disorders. The book was designed for communication specialists who work in medical centers, rehabilitation clinics, private practice, public schools, or any setting in which drug therapy may influence a client's communication. This chapter covers neurologic disorders that may affect speech and voice production. For each disorder, the authors provide a definition and cause; discuss the general features, symptoms, and signs; describe the features, symptoms, and signs of communication impairment associated with each disorder; list pharmacologic (drug) treatment for each disorder; and discuss the influence that drug treatment may have on communication. Each section also lists references for additional information. Disorders covered include Parkinson's disease, myasthenia gravis, amyotrophic lateral sclerosis (ALS), multiple sclerosis, Wilson's disease, cerebral palsy, Huntington's disease, and Tourette's syndrome. 4 tables. 63 references.

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Voice Source: in Roeser, R.J.; Pearson, D.W.; Tobey, E.A. Speech-Language Pathology Desk Reference. New York, NY: Thieme Medical Publishers, Inc. 1998. p. 321-383. Contact: Available from Thieme Medical Publishers, Inc. 333 Seventh Avenue, New York, NY 10001. (800) 782-3488. Fax (212) 947-0108. E-mail: [email protected]. Website: www.thieme.com. PRICE: $45.00 plus shipping and handling. ISBN: 0865776972. Summary: This chapter on voice and voice disorders is from a reference book for speech language pathologists. The book includes twelve chapters, each consisting predominantly of charts and figures that cover the topic under consideration. Topics covered in this chapter include amyotrophic lateral sclerosis (ALS) and its impact on the voice, apraxia of speech, artificial larynges, ataxic dysarthria, breathy whispered voice, cervical dystonia, cleft lip and palate classifications, congenital disorders of the larynx, cranial nerve assessment techniques, dystonia, exhalation, fundamental and formant frequencies, Tourette syndrome, laryngoscopy, muscles used in voice, laryngeal dimensions, laryngeal anatomy and physiology, myasthenia gravis, palate and face development during embryonic and fetal stages, Parkinson's disease, voice attributes, the classification of voice disorders, terminology of voice pathology, hoarseness, the

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neurophysiology of the voice, voice therapy, and a voice rating scale. The book includes a series of 22 color plates, most of which depict the vocal cords. 32 figures. 37 tables. •

Neurologic Disorders Affecting the Voice in Performance Source: in Sataloff, R.T., ed. Professional Voice: The Science and Art of Clinical Care. 2nd ed. San Diego, CA: Singular Publishing Group, Inc. 1997. p. 479-498. Contact: Available from Singular Publishing Group, Inc. 401 West 'A' Street, Suite 325, San Diego, CA 92101-7904. (800) 521-8545 or (619) 238-6777. Fax (800) 774-8398 or (619) 238-6789. E-mail: [email protected]. Website: www.singpub.com. PRICE: $325.00 plus shipping and handling. ISBN: 1565937287. Summary: This chapter, from a book on the clinical care of the professional voice, discusses neurologic disorders affecting the voice in performance. The complex functions necessary for normal voice function require coordinated interactions among multiple body systems. Neurologic dysfunction that impairs control of these interactions commonly causes voice dysfunction. The authors note that it is not unusual for voice disorders to be the presenting complaint in patients with neurologic disease. Topics include neurolaryngology, neuroanatomy and neurophysiology of phonation, neurological dysfunction and voice, vocal cord paralysis, dysarthria (imperfect articulation in speech), vocal tremor, Parkinson disease, postpolio syndrome, stuttering, myasthenia gravis, and other neurological conditions affecting voice performance, including amyotrophic lateral sclerosis, multiple sclerosis, Huntington's chorea, Gilles de la Tourette syndrome, cerebrovascular accident (stroke), quadriplegia, facial paralysis in singers and actors, headache, and dizziness. The authors conclude that familiarity with the latest concepts in neurolaryngology, clinical voice disorders, and a close working relationship between laryngologists and neurologists may optimize treatment. 5 figures. 31 references.

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Physical Disability and Sensory Impairment Source: in Griffiths, J. and Boyle, S. Colour Guide to Holistic Oral Care: A Practical Approach. Mosby-Year Book Europe. 1993. p. 131-150. Contact: Available from Mosby-Year Book Europe. Lynton House, 7-12 Tavistock Square, London WC1H 9LB, England. Telephone 0171-391 4471. Fax 0171-391 6598. ISBN: 0723417792. Summary: This chapter, from a textbook that outlines the role of the nurse in oral health care, discusses the oral care of people with physical disability or sensory impairment. The authors summarize the more common conditions that may affect manual dexterity, arm control, and mobility. Topics covered include the prevalence of physical disability; barriers to oral health; arthritis; brittle bone disease (osteogenesis imperfecta); rickets and osteomalacia; osteoporosis; Paget's disease (oteitis deformans); muscular dystrophies and myotonic disorders; myasthenia gravis; motor neurone disease; multiple sclerosis; Guillain-Barre syndrome; stroke (cerebrovascular accident); Bell's palsy; Parkinson's disease; cleft lip and palate; cerebral palsy; spina bifida and hydrocephalus; spinal injuries and trauma; head injury; epilepsy; and sensory impairment. 6 tables. 22 references. (AA-M).


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Neuromuscular Disorders Source: in Grundy, M.C.; Shaw, L.; and Hamilton, D.V. Illustrated Guide to Dental Care for the Medically Compromised Patient. St. Louis, MO: Mosby-Year Book, Inc. 1993. p. 87-88. Contact: Available from Mosby-Year Book, Inc. 11830 Westline Industrial Drive, St. Louis, MO 63146-9934. (800) 426-4545 or (314) 872-8370; Fax (800) 535-9935 or (314) 4321380; E-mail: [email protected]; http://www.mosby.com. PRICE: $24.95 plus shipping and handling. ISBN: 0815140223. Summary: This chapter, from an illustrated guide to dental care for medically compromised patients, discusses neuromuscular disorders. Topics covered include muscular dystrophy, myasthenia gravis, and Guillain-Barre syndrome. For each condition, the authors provide a brief description, the components of medical management, and suggestions for dental care.

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CHAPTER 8. MULTIMEDIA ON MYASTHENIA GRAVIS Overview In this chapter, we show you how to keep current on multimedia sources of information on myasthenia gravis. We start with sources that have been summarized by federal agencies, and then show you how to find bibliographic information catalogued by the National Library of Medicine.

Bibliography: Multimedia on Myasthenia Gravis The National Library of Medicine is a rich source of information on healthcare-related multimedia productions including slides, computer software, and databases. To access the multimedia database, go to the following Web site: http://locatorplus.gov/. Select “Search LOCATORplus.” Once in the search area, simply type in myasthenia gravis (or synonyms). Then, in the option box provided below the search box, select “Audiovisuals and Computer Files.” From there, you can choose to sort results by publication date, author, or relevance. The following multimedia has been indexed on myasthenia gravis: •

A Critique of experimental models of myasthenia gravis [videorecording] Source: National Institute of Neurological and Communicative Disorders and Stroke; Year: 1976; Format: Videorecording; [Bethesda, Md.]: The Institute; [Atlanta: for loan by National Medical Audiovisual Center, 1976?]

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Electroneurography: myasthenia gravis [slide] Source: Niagara Frontier District, New York State Chapter of the American Physical Therapy Association, Physical Therapy Association of the State of New York, Council of Licensed Physiotherapists of New York, incor; Year: 1978; Format: Slide; [Buffalo]: Communications in Learning, [1978]

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Ms. Tarbo, a lady with myasthenia gravis [electronic resource] Source: by Sharon Gomez; Year: 1989; Format: Electronic resource; Philadelphia, PA: J.B. Lippincott, c1989

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Multiple sclerosis and myasthenia gravis [videorecording]; Infectious disease; Epilepsy Source: Stephen Salloway; Year: 1998; Format: Videorecording; [Irvine, Calif.]: CME, c1998

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Myasthenia gravis [electronic resource] Source: AACN [and] Medi-Sim, Inc; Year: 1988; Format: Electronic resource; Edwardsville, KS: Medi-Sim, c1988


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Myasthenia gravis [electronic resource]. Year: 1996; Format: Electronic resource; Baltimore, MD: Williams & Wilkins, c1996

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Myasthenia gravis [motion picture]: (Erb-Goldflam syndrome) Source: from the Neurological Department of the Massachusetts General Hospital; Year: 1946; Format: Motion picture; United States: The Hospital, 1946

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Myasthenia gravis [videorecording] Source: Medical TV Center, Teaching Laboratories, School of Medicine, Univ. of North Carolina; Year: 1974; Format: Videorecording; Chapel Hill: The Center, [1973]

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Myasthenia gravis, new hope [motion picture] Source: produced by Medical Illustration and Audiovisual Education, Baylor College of Medicine; Year: 1980; Format: Motion picture; [S.l.]: Bernard M. Patten, c1980

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Pharmacological evidence for the contrast between myasthenia gravis and myotonia congenita [motion picture] Source: [Bellevue Hospital Neurological and Neuro-surgical Service]; produced by Sarah P. Shiras; Year: 1939; Format: Motion picture; [United States: The Service, 1939]

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The biology of myasthenia gravis [sound recording] Source: Lewis Rowland; Year: 1977; Format: Sound recording; Dallas, TX: Medisette, 1977

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The use of curare as a diagnostic test of myasthenia gravis [motion picture] Source: from the Neuropsychiatric Departments of the University of Nebraska and Bishop Clarkson Memorial Hospital; by A.E. Bennett and Paul T. Cash; Year: 1943; Format: Motion picture; [United States]: Psychological Cinema Register of the Pennsylvania State College, [1943]

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Thoracoscopic thymectomy for myasthenia gravis in children [videorecording] Source: Evans Valerie, Peter C. Kim; Year: 2003; Format: Videorecording; Woodbury, CT: Cine-Med, Inc., 2003

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Transcervical-transsternal maximal thymectomy for myasthenia gravis [videorecording]: surgical technique Source: video production by Center for Biomedical Communications, College of Physicians & Surgeons, Columbia University; Year: 1989; Format: Videorecording; [United States: s.n.], c1989

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CHAPTER 9. PERIODICALS AND NEWS ON MYASTHENIA GRAVIS Overview In this chapter, we suggest a number of news sources and present various periodicals that cover myasthenia gravis.

News Services and Press Releases One of the simplest ways of tracking press releases on myasthenia gravis 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 “myasthenia gravis” (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 myasthenia gravis. 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 “myasthenia gravis” (or synonyms). The following was recently listed in this archive for myasthenia gravis: •

Myasthenia gravis raises risk of adverse pregnancy outcomes Source: Reuters Medical News Date: November 24, 2003


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Aventis urges extreme caution with Ketek in patients with myasthenia gravis Source: Reuters Medical News Date: April 15, 2003

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Myasthenia gravis responds to high-dose cyclophosphamide immune "rebooting" Source: Reuters Industry Breifing Date: January 27, 2003

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CD40L blockade effectively suppresses myasthenia gravis in animal model Source: Reuters Medical News Date: July 02, 2001

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Prognosis of myasthenia gravis generally favorable in the elderly Source: Reuters Medical News Date: November 23, 2000

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Antibody to T-cell receptor gene prevents autoimmune attack in mouse model of myasthenia gravis Source: Reuters Medical News Date: October 19, 1999

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Intravenous IgM suppresses autoimmune antibodies in mice with myasthenia gravis Source: Reuters Medical News Date: August 25, 1999

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Thymectomy for myasthenia gravis may increase risk of autoimmune disease Source: Reuters Medical News Date: June 07, 1999

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Myasthenia Gravis Can Present As Isolated Dyspnea Source: Reuters Medical News Date: October 20, 1997 The NIH

Within MEDLINEplus, the NIH has made an agreement with the New York Times Syndicate, the AP News Service, and Reuters to deliver news that can be browsed by the public. Search news releases at http://www.nlm.nih.gov/medlineplus/alphanews_a.html. MEDLINEplus allows you to browse across an alphabetical index. Or you can search by date at the following Web page: http://www.nlm.nih.gov/medlineplus/newsbydate.html. Often, news items are indexed by MEDLINEplus within its search engine. Business Wire Business Wire is similar to PR Newswire. To access this archive, simply go to http://www.businesswire.com/. You can scan the news by industry category or company name. Market Wire Market Wire is more focused on technology than the other wires. To browse the latest press releases by topic, such as alternative medicine, biotechnology, fitness, healthcare, legal, nutrition, and pharmaceuticals, access Market Wire’s Medical/Health channel at

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http://www.marketwire.com/mw/release_index?channel=MedicalHealth. Or simply go to Market Wire’s home page at http://www.marketwire.com/mw/home, type “myasthenia gravis” (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 “myasthenia gravis” (or synonyms). If you know the name of a company that is relevant to myasthenia gravis, you can go to any stock trading Web site (such as http://www.etrade.com/) and search for the company name there. News items across various news sources are reported on indicated hyperlinks. Google offers a similar service at http://news.google.com/. BBC Covering news from a more European perspective, the British Broadcasting Corporation (BBC) allows the public free access to their news archive located at http://www.bbc.co.uk/. Search by “myasthenia gravis” (or synonyms).

Newsletter Articles Use the Combined Health Information Database, and limit your search criteria to “newsletter articles.” Again, you will need to use the “Detailed Search” option. Go directly to the following hyperlink: http://chid.nih.gov/detail/detail.html. Go to the bottom of the search page where “You may refine your search by.” Select the dates and language that you prefer. For the format option, select “Newsletter Article.” Type “myasthenia gravis” (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 myasthenia gravis: •

Digestion: The Ups and Downs of Swallowing Source: Harvard Health Letter. 21(11): 3. September 1996. Contact: Available from Harvard Health Letter. P.O. Box 380, Boston, MA 02117. (800) 829-9045 or (617) 432-1485. Summary: This brief health newsletter article reviews swallowing and swallowing disorders. The author first summarizes the physiology of a swallow, then defines different types of related disorders, including esophageal dysphagia (the sensation of food sticking in the neck or chest), esophageal spasms (chest pain and the sensation that food is getting caught), achalasia (problems with the lower esophageal sphincter not relaxing and letting food into the stomach), benign peptic stricture (usually due to years of gastroesophageal reflux), esophageal cancer, Schatzki's ring (a band of tissue that protrudes into the lower esophagus), and neurologic or degenerative diseases, such as Parkinson or Lou Gehrig disease, multiple sclerosis, or myasthenia gravis. One sidebar


reviews the symptom of globus and its causes. The author concludes by reassuring readers that everyone occasionally experiences swallowing discomfort, usually the result of gulping food too quickly during a stressful time.

Academic Periodicals covering Myasthenia Gravis Numerous periodicals are currently indexed within the National Library of Medicine’s PubMed database that are known to publish articles relating to myasthenia gravis. In addition to these sources, you can search for articles covering myasthenia gravis that have been published by any of the periodicals listed in previous chapters. To find the latest studies published, go to http://www.ncbi.nlm.nih.gov/pubmed, type the name of the periodical into the search box, and click “Go.” If you want complete details about the historical contents of a journal, you can also visit the following Web site: http://www.ncbi.nlm.nih.gov/entrez/jrbrowser.cgi. Here, type in the name of the journal or its abbreviation, and you will receive an index of published articles. At http://locatorplus.gov/, you can retrieve more indexing information on medical periodicals (e.g. the name of the publisher). Select the button “Search LOCATORplus.” Then type in the name of the journal and select the advanced search option “Journal Title Search.”

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CHAPTER 10. RESEARCHING MEDICATIONS Overview While a number of hard copy or CD-ROM resources are available for researching medications, a more flexible method is to use Internet-based databases. Broadly speaking, there are two sources of information on approved medications: public sources and private sources. We will emphasize free-to-use public sources.

U.S. Pharmacopeia Because of historical investments by various organizations and the emergence of the Internet, it has become rather simple to learn about the medications recommended for myasthenia gravis. One such source is the United States Pharmacopeia. In 1820, eleven physicians met in Washington, D.C. to establish the first compendium of standard drugs for the United States. They called this compendium the U.S. Pharmacopeia (USP). Today, the USP is a non-profit organization consisting of 800 volunteer scientists, eleven elected officials, and 400 representatives of state associations and colleges of medicine and pharmacy. The USP is located in Rockville, Maryland, and its home page is located at http://www.usp.org/. The USP currently provides standards for over 3,700 medications. The resulting USP DI Advice for the Patient can be accessed through the National Library of Medicine of the National Institutes of Health. The database is partially derived from lists of federally approved medications in the Food and Drug Administration’s (FDA) Drug Approvals database, located at http://www.fda.gov/cder/da/da.htm. While the FDA database is rather large and difficult to navigate, the Phamacopeia is both user-friendly and free to use. It covers more than 9,000 prescription and over-the-counter medications. To access this database, simply type the following hyperlink into your Web browser: http://www.nlm.nih.gov/medlineplus/druginformation.html. To view examples of a given medication (brand names, category, description, preparation, proper use, precautions, side effects, etc.), simply follow the hyperlinks indicated within the United States Pharmacopeia (USP). Below, we have compiled a list of medications associated with myasthenia gravis. If you would like more information on a particular medication, the provided hyperlinks will direct you to ample documentation (e.g. typical dosage, side effects, drug-interaction risks, etc.).


The following drugs have been mentioned in the Pharmacopeia and other sources as being potentially applicable to myasthenia gravis: Aminoglycosides •

Systemic - U.S. Brands: Amikin; Garamycin; G-Mycin; Jenamicin; Kantrex; Nebcin; Netromycin http://www.nlm.nih.gov/medlineplus/druginfo/uspdi/202027.html

Antimyasthenics •

Systemic - U.S. Brands: Mestinon; Mestinon Timespans; Mytelase Caplets; Prostigmin; Regonol http://www.nlm.nih.gov/medlineplus/druginfo/uspdi/202065.html

Azathioprine •

Systemic - U.S. Brands: Imuran http://www.nlm.nih.gov/medlineplus/druginfo/uspdi/202077.html

Corticosteroids •

Dental - U.S. Brands: Kenalog in Orabase; Orabase-HCA; Oracort; Oralone http://www.nlm.nih.gov/medlineplus/druginfo/uspdi/202010.html

•

Inhalation - U.S. Brands: AeroBid; AeroBid-M; Azmacort; Beclovent; Decadron Respihaler; Pulmicort Respules; Pulmicort Turbuhaler; Vanceril; Vanceril 84 mcg Double Strength http://www.nlm.nih.gov/medlineplus/druginfo/uspdi/202011.html

•

Nasal - U.S. Brands: Beconase; Beconase AQ; Dexacort Turbinaire; Flonase; Nasacort; Nasacort AQ; Nasalide; Nasarel; Nasonex; Rhinocort; Vancenase; Vancenase AQ 84 mcg; Vancenase pockethaler http://www.nlm.nih.gov/medlineplus/druginfo/uspdi/202012.html

•

Ophthalmic - U.S. Brands: AK-Dex; AK-Pred; AK-Tate; Baldex; Decadron; Dexair; Dexotic; Econopred; Econopred Plus; Eflone; Flarex; Fluor-Op; FML Forte; FML Liquifilm; FML S.O.P.; HMS Liquifilm; Inflamase Forte; Inflamase Mild; I-Pred; Lite Pred; Maxidex; Ocu-Dex; Ocu-Pred; Ocu-Pr http://www.nlm.nih.gov/medlineplus/druginfo/uspdi/202013.html

•

Otic - U.S. Brands: Decadron http://www.nlm.nih.gov/medlineplus/druginfo/uspdi/202014.html

•

Rectal - U.S. Brands: Anucort-HC; Anu-Med HC; Anuprep HC; Anusol-HC; Anutone-HC; Anuzone-HC; Cort-Dome; Cortenema; Cortifoam; Hemorrhoidal HC; Hemril-HC Uniserts; Proctocort; Proctosol-HC; Rectosol-HC http://www.nlm.nih.gov/medlineplus/druginfo/uspdi/203366.html

Cyclophosphamide •

Systemic - U.S. Brands: Cytoxan; Neosar http://www.nlm.nih.gov/medlineplus/druginfo/uspdi/202174.html

Cyclosporine •

Systemic - U.S. Brands: Neoral; Sandimmune; SangCya http://www.nlm.nih.gov/medlineplus/druginfo/uspdi/202176.html

Researching Medications

139

Immune Globulin Intravenous (Human) •

Systemic - U.S. Brands: Iveegam; Sandoglobulin; Venoglobulin-I; VenoglobulinS http://www.nlm.nih.gov/medlineplus/druginfo/uspdi/202641.html

Tetracyclines •

Systemic http://www.nlm.nih.gov/medlineplus/druginfo/uspdi/202641.html

•

Systemic - U.S. Brands: Achromycin V; Declomycin; Doryx; Dynacin; Minocin; Monodox; Terramycin; Vibramycin; Vibra-Tabs http://www.nlm.nih.gov/medlineplus/druginfo/uspdi/202552.html

•

Topical - U.S. Brands: Achromycin; Aureomycin; Meclan; Topicycline http://www.nlm.nih.gov/medlineplus/druginfo/uspdi/202553.html

Commercial Databases In addition to the medications listed in the USP above, a number of commercial sites are available by subscription to physicians and their institutions. Or, you may be able to access these sources from your local medical library.

Mosby’s Drug Consult Mosby’s Drug Consult database (also available on CD-ROM and book format) covers 45,000 drug products including generics and international brands. It provides prescribing information, drug interactions, and patient information. Subscription information is available at the following hyperlink: http://www.mosbysdrugconsult.com/.

PDRhealth The PDRhealth database is a free-to-use, drug information search engine that has been written for the public in layman’s terms. It contains FDA-approved drug information adapted from the Physicians’ Desk Reference (PDR) database. PDRhealth can be searched by brand name, generic name, or indication. It features multiple drug interactions reports. Search PDRhealth at http://www.pdrhealth.com/drug_info/index.html. Other Web Sites Drugs.com (www.drugs.com) reproduces the information in the Pharmacopeia as well as commercial information. You may also want to consider the Web site of the Medical Letter, Inc. (http://www.medletter.com/) which allows users to download articles on various drugs and therapeutics for a nominal fee.


Researching Orphan Drugs Although the list of orphan drugs is revised on a daily basis, you can quickly research orphan drugs that might be applicable to myasthenia gravis by using the database managed by the National Organization for Rare Disorders, Inc. (NORD), at http://www.rarediseases.org/. Scroll down the page, and on the left toolbar, click on “Orphan Drug Designation Database.” On this page (http://www.rarediseases.org/search/noddsearch.html), type “myasthenia gravis” (or synonyms) into the search box, and click “Submit Query.” When you receive your results, note that not all of the drugs may be relevant, as some may have been withdrawn from orphan status. Write down or print out the name of each drug and the relevant contact information. From there, visit the Pharmacopeia Web site and type the name of each orphan drug into the search box at http://www.nlm.nih.gov/medlineplus/druginformation.html. You may need to contact the sponsor or NORD for further information. NORD conducts “early access programs for investigational new drugs (IND) under the Food and Drug Administration’s (FDA’s) approval ‘Treatment INDs’ programs which allow for a limited number of individuals to receive investigational drugs before FDA marketing approval.” If the orphan product about which you are seeking information is approved for marketing, information on side effects can be found on the product’s label. If the product is not approved, you may need to contact the sponsor. The following is a list of orphan drugs currently listed in the NORD Orphan Drug Designation Database for myasthenia gravis: •

Recombinant Human Alpha-Fetoprotein (rhAFP) (trade name: NONE Assigned) http://www.rarediseases.org/nord/search/nodd_full?code=1198

•

Recombinant Human Alpha-Fetoprotein http://www.rarediseases.org/nord/search/nodd_full?code=1123

If you have any questions about a medical treatment, the FDA may have an office near you. Look for their number in the blue pages of the phone book. You can also contact the FDA through its toll-free number, 1-888-INFO-FDA (1-888-463-6332), or on the World Wide Web at www.fda.gov.

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APPENDICES

143

APPENDIX A. PHYSICIAN RESOURCES Overview In this chapter, we focus on databases and Internet-based guidelines and information resources created or written for a professional audience.

NIH Guidelines Commonly referred to as “clinical” or “professional” guidelines, the National Institutes of Health publish physician guidelines for the most common diseases. Publications are available at the following by relevant Institute12: •

Office of the Director (OD); guidelines consolidated across agencies available at http://www.nih.gov/health/consumer/conkey.htm

•

National Institute of General Medical Sciences (NIGMS); fact sheets available at http://www.nigms.nih.gov/news/facts/

•

National Library of Medicine (NLM); extensive encyclopedia (A.D.A.M., Inc.) with guidelines: http://www.nlm.nih.gov/medlineplus/healthtopics.html

•

National Cancer Institute (NCI); guidelines available at http://www.cancer.gov/cancerinfo/list.aspx?viewid=5f35036e-5497-4d86-8c2c714a9f7c8d25

•

National Eye Institute (NEI); guidelines available at http://www.nei.nih.gov/order/index.htm

•

National Heart, Lung, and Blood Institute (NHLBI); guidelines available at http://www.nhlbi.nih.gov/guidelines/index.htm

•

National Human Genome Research Institute (NHGRI); research available at http://www.genome.gov/page.cfm?pageID=10000375

•

National Institute on Aging (NIA); guidelines available at http://www.nia.nih.gov/health/

12

These publications are typically written by one or more of the various NIH Institutes.


•

National Institute on Alcohol Abuse and Alcoholism (NIAAA); guidelines available at http://www.niaaa.nih.gov/publications/publications.htm

•

National Institute of Allergy and Infectious Diseases (NIAID); guidelines available at http://www.niaid.nih.gov/publications/

•

National Institute of Arthritis and Musculoskeletal and Skin Diseases (NIAMS); fact sheets and guidelines available at http://www.niams.nih.gov/hi/index.htm

•

National Institute of Child Health and Human Development (NICHD); guidelines available at http://www.nichd.nih.gov/publications/pubskey.cfm

•

National Institute on Deafness and Other Communication Disorders (NIDCD); fact sheets and guidelines at http://www.nidcd.nih.gov/health/

•

National Institute of Dental and Craniofacial Research (NIDCR); guidelines available at http://www.nidr.nih.gov/health/

•

National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK); guidelines available at http://www.niddk.nih.gov/health/health.htm

•

National Institute on Drug Abuse (NIDA); guidelines available at http://www.nida.nih.gov/DrugAbuse.html

•

National Institute of Environmental Health Sciences (NIEHS); environmental health information available at http://www.niehs.nih.gov/external/facts.htm

•

National Institute of Mental Health (NIMH); guidelines available at http://www.nimh.nih.gov/practitioners/index.cfm

•

National Institute of Neurological Disorders and Stroke (NINDS); neurological disorder information pages available at http://www.ninds.nih.gov/health_and_medical/disorder_index.htm

•

National Institute of Nursing Research (NINR); publications on selected illnesses at http://www.nih.gov/ninr/news-info/publications.html

•

National Institute of Biomedical Imaging and Bioengineering; general information at http://grants.nih.gov/grants/becon/becon_info.htm

•

Center for Information Technology (CIT); referrals to other agencies based on keyword searches available at http://kb.nih.gov/www_query_main.asp

•

National Center for Complementary and Alternative Medicine (NCCAM); health information available at http://nccam.nih.gov/health/

•

National Center for Research Resources (NCRR); various information directories available at http://www.ncrr.nih.gov/publications.asp

•

Office of Rare Diseases; various fact sheets available at http://rarediseases.info.nih.gov/html/resources/rep_pubs.html

•

Centers for Disease Control and Prevention; various fact sheets on infectious diseases available at http://www.cdc.gov/publications.htm

Physician Resources 145

NIH Databases In addition to the various Institutes of Health that publish professional guidelines, the NIH has designed a number of databases for professionals.13 Physician-oriented resources provide a wide variety of information related to the biomedical and health sciences, both past and present. The format of these resources varies. Searchable databases, bibliographic citations, full-text articles (when available), archival collections, and images are all available. The following are referenced by the National Library of Medicine:14 •

Bioethics: Access to published literature on the ethical, legal, and public policy issues surrounding healthcare and biomedical research. This information is provided in conjunction with the Kennedy Institute of Ethics located at Georgetown University, Washington, D.C.: http://www.nlm.nih.gov/databases/databases_bioethics.html

•

HIV/AIDS Resources: Describes various links and databases dedicated to HIV/AIDS research: http://www.nlm.nih.gov/pubs/factsheets/aidsinfs.html

•

NLM Online Exhibitions: Describes “Exhibitions in the History of Medicine”: http://www.nlm.nih.gov/exhibition/exhibition.html. Additional resources for historical scholarship in medicine: http://www.nlm.nih.gov/hmd/hmd.html

•

Biotechnology Information: Access to public databases. The National Center for Biotechnology Information conducts research in computational biology, develops software tools for analyzing genome data, and disseminates biomedical information for the better understanding of molecular processes affecting human health and disease: http://www.ncbi.nlm.nih.gov/

•

Population Information: The National Library of Medicine provides access to worldwide coverage of population, family planning, and related health issues, including family planning technology and programs, fertility, and population law and policy: http://www.nlm.nih.gov/databases/databases_population.html

•

Cancer Information: Access to cancer-oriented databases: http://www.nlm.nih.gov/databases/databases_cancer.html

•

Profiles in Science: Offering the archival collections of prominent twentieth-century biomedical scientists to the public through modern digital technology: http://www.profiles.nlm.nih.gov/

•

Chemical Information: Provides links to various chemical databases and references: http://sis.nlm.nih.gov/Chem/ChemMain.html

•

Clinical Alerts: Reports the release of findings from the NIH-funded clinical trials where such release could significantly affect morbidity and mortality: http://www.nlm.nih.gov/databases/alerts/clinical_alerts.html

•

Space Life Sciences: Provides links and information to space-based research (including NASA): http://www.nlm.nih.gov/databases/databases_space.html

•

MEDLINE: Bibliographic database covering the fields of medicine, nursing, dentistry, veterinary medicine, the healthcare system, and the pre-clinical sciences: http://www.nlm.nih.gov/databases/databases_medline.html

13 Remember, for the general public, the National Library of Medicine recommends the databases referenced in MEDLINEplus (http://medlineplus.gov/ or http://www.nlm.nih.gov/medlineplus/databases.html). 14 See http://www.nlm.nih.gov/databases/databases.html.


•

Toxicology and Environmental Health Information (TOXNET): Databases covering toxicology and environmental health: http://sis.nlm.nih.gov/Tox/ToxMain.html

•

Visible Human Interface: Anatomically detailed, three-dimensional representations of normal male and female human bodies: http://www.nlm.nih.gov/research/visible/visible_human.html

The NLM Gateway15 The NLM (National Library of Medicine) Gateway is a Web-based system that lets users search simultaneously in multiple retrieval systems at the U.S. National Library of Medicine (NLM). It allows users of NLM services to initiate searches from one Web interface, providing one-stop searching for many of NLM’s information resources or databases.16 To use the NLM Gateway, simply go to the search site at http://gateway.nlm.nih.gov/gw/Cmd. Type “myasthenia gravis” (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 10812 151 169 5 0 11137

HSTAT17 HSTAT is a free, Web-based resource that provides access to full-text documents used in healthcare decision-making.18 These documents include clinical practice guidelines, quickreference guides for clinicians, consumer health brochures, evidence reports and technology assessments from the Agency for Healthcare Research and Quality (AHRQ), as well as AHRQ’s Put Prevention Into Practice.19 Simply search by “myasthenia gravis” (or synonyms) at the following Web site: http://text.nlm.nih.gov.

15

Adapted from NLM: http://gateway.nlm.nih.gov/gw/Cmd?Overview.x.

16

The NLM Gateway is currently being developed by the Lister Hill National Center for Biomedical Communications (LHNCBC) at the National Library of Medicine (NLM) of the National Institutes of Health (NIH). 17 Adapted from HSTAT: http://www.nlm.nih.gov/pubs/factsheets/hstat.html. 18 19

The HSTAT URL is http://hstat.nlm.nih.gov/.

Other important documents in HSTAT include: the National Institutes of Health (NIH) Consensus Conference Reports and Technology Assessment Reports; the HIV/AIDS Treatment Information Service (ATIS) resource documents; the Substance Abuse and Mental Health Services Administration's Center for Substance Abuse Treatment (SAMHSA/CSAT) Treatment Improvement Protocols (TIP) and Center for Substance Abuse Prevention (SAMHSA/CSAP) Prevention Enhancement Protocols System (PEPS); the Public Health Service (PHS) Preventive Services Task Force's Guide to Clinical Preventive Services; the independent, nonfederal Task Force on Community Services’ Guide to Community Preventive Services; and the Health Technology Advisory Committee (HTAC) of the Minnesota Health Care Commission (MHCC) health technology evaluations.


Coffee Break: Tutorials for Biologists20 Coffee Break is a general healthcare site that takes a scientific view of the news and covers recent breakthroughs in biology that may one day assist physicians in developing treatments. Here you will find a collection of short reports on recent biological discoveries. Each report incorporates interactive tutorials that demonstrate how bioinformatics tools are used as a part of the research process. Currently, all Coffee Breaks are written by NCBI staff.21 Each report is about 400 words and is usually based on a discovery reported in one or more articles from recently published, peer-reviewed literature.22 This site has new articles every few weeks, so it can be considered an online magazine of sorts. It is intended for general background information. You can access the Coffee Break Web site at the following hyperlink: http://www.ncbi.nlm.nih.gov/Coffeebreak/.

Other Commercial Databases In addition to resources maintained by official agencies, other databases exist that are commercial ventures addressing medical professionals. Here are some examples that may interest you: •

CliniWeb International: Index and table of contents to selected clinical information on the Internet; see http://www.ohsu.edu/cliniweb/.

•

Medical World Search: Searches full text from thousands of selected medical sites on the Internet; see http://www.mwsearch.com/.

The Genome Project and Myasthenia Gravis In the following section, we will discuss databases and references which relate to the Genome Project and myasthenia gravis. Online Mendelian Inheritance in Man (OMIM) The Online Mendelian Inheritance in Man (OMIM) database is a catalog of human genes and genetic disorders authored and edited by Dr. Victor A. McKusick and his colleagues at Johns Hopkins and elsewhere. OMIM was developed for the World Wide Web by the National Center for Biotechnology Information (NCBI).23 The database contains textual information, pictures, and reference information. It also contains copious links to NCBI’s Entrez database of MEDLINE articles and sequence information.

20 Adapted 21

from http://www.ncbi.nlm.nih.gov/Coffeebreak/Archive/FAQ.html.

The figure that accompanies each article is frequently supplied by an expert external to NCBI, in which case the source of the figure is cited. The result is an interactive tutorial that tells a biological story. 22 After a brief introduction that sets the work described into a broader context, the report focuses on how a molecular understanding can provide explanations of observed biology and lead to therapies for diseases. Each vignette is accompanied by a figure and hypertext links that lead to a series of pages that interactively show how NCBI tools and resources are used in the research process. 23 Adapted from http://www.ncbi.nlm.nih.gov/. Established in 1988 as a national resource for molecular biology information, NCBI creates public databases, conducts research in computational biology, develops software tools for analyzing genome data, and disseminates biomedical information--all for the better understanding of molecular processes affecting human health and disease.


To search the database, go to http://www.ncbi.nlm.nih.gov/Omim/searchomim.html. Type “myasthenia gravis” (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 myasthenia gravis: •

Myasthenia Gravis, Familial Infantile; FIMG Web site: http://www.ncbi.nlm.nih.gov/htbin-post/Omim/dispmim?254210

•

Myasthenia Gravis, Familial Infantile, 1 Web site: http://www.ncbi.nlm.nih.gov/htbin-post/Omim/dispmim?605809

•

Myasthenia Gravis; MG Web site: http://www.ncbi.nlm.nih.gov/htbin-post/Omim/dispmim?254200

•

Myasthenic Syndrome, Slow-Channel Congenital; SCCMS Web site: http://www.ncbi.nlm.nih.gov/htbin-post/Omim/dispmim?601462

•

Myasthenia Gravis with Thymus Hyperplasia Web site: http://www.ncbi.nlm.nih.gov/htbin-post/Omim/dispmim?607085 Genes and Disease (NCBI - Map)

The Genes and Disease database is produced by the National Center for Biotechnology Information of the National Library of Medicine at the National Institutes of Health. This Web site categorizes each disorder by system of the body. Go to http://www.ncbi.nlm.nih.gov/disease/, and browse the system pages to have a full view of important conditions linked to human genes. Since this site is regularly updated, you may wish to revisit it from time to time. The following systems and associated disorders are addressed: •

Cancer: Uncontrolled cell division. Examples: Breast and ovarian cancer, Burkitt lymphoma, chronic myeloid leukemia, colon cancer, lung cancer, malignant melanoma, multiple endocrine neoplasia, neurofibromatosis, p53 tumor suppressor, pancreatic cancer, prostate cancer, Ras oncogene, RB: retinoblastoma, von Hippel-Lindau syndrome. Web site: http://www.ncbi.nlm.nih.gov/disease/Cancer.html

•

Immune System: Fights invaders. Examples: Asthma, autoimmune polyglandular syndrome, Crohn’s disease, DiGeorge syndrome, familial Mediterranean fever, immunodeficiency with Hyper-IgM, severe combined immunodeficiency. Web site: http://www.ncbi.nlm.nih.gov/disease/Immune.html

•

Metabolism: Food and energy. Examples: Adreno-leukodystrophy, atherosclerosis, Best disease, Gaucher disease, glucose galactose malabsorption, gyrate atrophy, juvenile-onset diabetes, obesity, paroxysmal nocturnal hemoglobinuria, phenylketonuria, Refsum disease, Tangier disease, Tay-Sachs disease. Web site: http://www.ncbi.nlm.nih.gov/disease/Metabolism.html

•

Muscle and Bone: Movement and growth. Examples: Duchenne muscular dystrophy, Ellis-van Creveld syndrome, Marfan


syndrome, myotonic dystrophy, spinal muscular atrophy. Web site: http://www.ncbi.nlm.nih.gov/disease/Muscle.html •

Nervous System: Mind and body. Examples: Alzheimer disease, amyotrophic lateral sclerosis, Angelman syndrome, Charcot-Marie-Tooth disease, epilepsy, essential tremor, fragile X syndrome, Friedreich’s ataxia, Huntington disease, Niemann-Pick disease, Parkinson disease, Prader-Willi syndrome, Rett syndrome, spinocerebellar atrophy, Williams syndrome. Web site: http://www.ncbi.nlm.nih.gov/disease/Brain.html

•

Signals: Cellular messages. Examples: Ataxia telangiectasia, Cockayne syndrome, glaucoma, male-patterned baldness, SRY: sex determination, tuberous sclerosis, Waardenburg syndrome, Werner syndrome. Web site: http://www.ncbi.nlm.nih.gov/disease/Signals.html

•

Transporters: Pumps and channels. Examples: Cystic fibrosis, deafness, diastrophic dysplasia, Hemophilia A, long-QT syndrome, Menkes syndrome, Pendred syndrome, polycystic kidney disease, sickle cell anemia, Wilson’s disease, Zellweger syndrome. Web site: http://www.ncbi.nlm.nih.gov/disease/Transporters.html Entrez

Entrez is a search and retrieval system that integrates several linked databases at the National Center for Biotechnology Information (NCBI). These databases include nucleotide sequences, protein sequences, macromolecular structures, whole genomes, and MEDLINE through PubMed. Entrez provides access to the following databases: •

3D Domains: Domains from Entrez Structure, Web site: http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=geo

•

Books: Online books, Web site: http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=books

•

Genome: Complete genome assemblies, Web site: http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=Genome

•

NCBI’s Protein Sequence Information Survey Results: Web site: http://www.ncbi.nlm.nih.gov/About/proteinsurvey/

•

Nucleotide Sequence Database (Genbank): Web site: http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=Nucleotide

•

OMIM: Online Mendelian Inheritance in Man, Web site: http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=OMIM

•

PopSet: Population study data sets, Web site: http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=Popset

•

ProbeSet: Gene Expression Omnibus (GEO), Web site: http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=geo

•

Protein Sequence Database: Web site: http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=Protein


•

PubMed: Biomedical literature (PubMed), Web site: http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed

•

Structure: Three-dimensional macromolecular structures, Web site: http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=Structure

•

Taxonomy: Organisms in GenBank, Web site: http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=Taxonomy

To access the Entrez system at the National Center for Biotechnology Information, go to http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?CMD=search&DB=genome, and then select the database that you would like to search. The databases available are listed in the drop box next to “Search.” Enter “myasthenia gravis” (or synonyms) into the search box and click “Go.” Jablonski’s Multiple Congenital Anomaly/Mental Retardation (MCA/MR) Syndromes Database24 This online resource has been developed to facilitate the identification and differentiation of syndromic entities. Special attention is given to the type of information that is usually limited or completely omitted in existing reference sources due to space limitations of the printed form. At http://www.nlm.nih.gov/mesh/jablonski/syndrome_toc/toc_a.html, you can search across syndromes using an alphabetical index. Search by keywords at http://www.nlm.nih.gov/mesh/jablonski/syndrome_db.html. The Genome Database25 Established at Johns Hopkins University in Baltimore, Maryland in 1990, the Genome Database (GDB) is the official central repository for genomic mapping data resulting from the Human Genome Initiative. In the spring of 1999, the Bioinformatics Supercomputing Centre (BiSC) at the Hospital for Sick Children in Toronto, Ontario assumed the management of GDB. The Human Genome Initiative is a worldwide research effort focusing on structural analysis of human DNA to determine the location and sequence of the estimated 100,000 human genes. In support of this project, GDB stores and curates data generated by researchers worldwide who are engaged in the mapping effort of the Human Genome Project (HGP). GDB’s mission is to provide scientists with an encyclopedia of the human genome which is continually revised and updated to reflect the current state of scientific knowledge. Although GDB has historically focused on gene mapping, its focus will broaden as the Genome Project moves from mapping to sequence, and finally, to functional analysis. To access the GDB, simply go to the following hyperlink: http://www.gdb.org/. Search “All Biological Data” by “Keyword.” Type “myasthenia gravis” (or synonyms) into the search box, and review the results. If more than one word is used in the search box, then separate each one with the word “and” or “or” (using “or” might be useful when using synonyms). 24 Adapted from the National Library of Medicine: http://www.nlm.nih.gov/mesh/jablonski/about_syndrome.html. 25 Adapted from the Genome Database: http://gdbwww.gdb.org/gdb/aboutGDB.html - mission.


153

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 myasthenia gravis can appear at any moment and be published by a number of sources, the best approach to finding guidelines is to systematically scan the Internetbased 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 myasthenia gravis. 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 myasthenia gravis. 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 “myasthenia gravis”:


•

Guides on myasthenia gravis Myasthenia Gravis http://www.nlm.nih.gov/medlineplus/myastheniagravis.html Myasthenia Gravis http://www.nlm.nih.gov/medlineplus/tutorials/myastheniagravisloader.html

•

Other guides Amyotrophic Lateral Sclerosis http://www.nlm.nih.gov/medlineplus/amyotrophiclateralsclerosis.html Autoimmune Diseases http://www.nlm.nih.gov/medlineplus/autoimmunediseases.html Muscular Dystrophy http://www.nlm.nih.gov/medlineplus/musculardystrophy.html Neuromuscular Disorders http://www.nlm.nih.gov/medlineplus/neuromusculardisorders.html

Within the health topic page dedicated to myasthenia gravis, the following was listed: •

General/Overviews Frequently Asked Questions about Myasthenia Gravis http://www.4woman.gov/faq/mgravis.pdf

•

Diagnosis/Symptoms Creatine Kinase Test Source: Muscular Dystrophy Association http://www.mdausa.org/publications/Quest/q71ss-cktest.html Electromyography and Nerve Conduction Velocities Source: Muscular Dystrophy Association http://www.mdausa.org/publications/Quest/q75ss.html

•

Treatment Imuran Source: Myasthenia Gravis Foundation of America http://www.myasthenia.org/information/Imuran.htm Intravenous Immunoglobulin: Common Questions Patients Ask about IVIg Therapy in Myasthenia Gravis http://www.myasthenia.org/information/IVIG.pdf Mestinon http://www.myasthenia.org/information/mestinon.pdf Mycophenolate Mofetil http://www.myasthenia.org/information/CellCept.pdf

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Plasmapheresis and Autoimmune Disease Source: Muscular Dystrophy Association http://www.mdausa.org/publications/fa-plasmaph.html?NS-searchset=/371cc/aaaa005J41ccc8e&NS-doc-offset=7& Prednisone http://www.myasthenia.org/information/prednisone.pdf •

Nutrition Nutrition and Myasthenia Gravis http://www.myasthenia.org/information/Nutrition.pdf

•

Coping Home Injury Prevention http://www.myasthenia.org/information/Home_Injury_Protection.pdf Safety and Myasthenia Gravis Source: Myasthenia Gravis Foundation of America http://www.myasthenia.org/information/safety.htm

•

Specific Conditions/Aspects Drugs to be Avoided or Taken with Caution in Myasthenia Gravis Source: Myasthenia Gravis Foundation of America http://www.myasthenia.org/information/alert.htm Emergency Management of Myasthenia Gravis http://www.myasthenia.org/information/emergency.pdf Keeping Your Focus: Eye Care Source: Muscular Dystrophy Association http://www.mdausa.org/publications/Quest/q76eyecare.html

•

Latest News Muscle Disease Tied to Pregnancy Problems Source: 11/24/2003, Reuters Health http://www.nlm.nih.gov//www.nlm.nih.gov/medlineplus/news/fullstory_14808 .html

•

Organizations American Autoimmune Related Diseases Association http://www.aarda.org/ Muscular Dystrophy Association http://www.mdausa.org/ Myasthenia Gravis Foundation of America http://www.myasthenia.org/index.htm National Institute of Neurological Disorders and Stroke http://www.ninds.nih.gov/


•

Research New Drug Shows Promise in MG and Other Autoimmune Disorders Source: Muscular Dystrophy Association http://www.mdausa.org/news/010226newdrugmg.html NIAMS Scientists Find Biochemical “Switch” Directs Muscle Building Source: National Institute of Arthritis and Musculoskeletal and Skin Diseases http://www.nih.gov/news/pr/sep2002/niams-25.htm Researchers Treat Muscle Disease with Vaccine: Studies Promising for Myasthenia Gravis, Other Autoimmune Diseases Source: Muscular Dystrophy Association http://www.mdausa.org/news/000106mgvacc.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 myasthenia gravis. 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: •

Emergency Management of Myasthenia Gravis: A Guide to Pre-Hospital Care Source: Chicago, IL: Myesthenia Graves Foundation of America, Inc. 1992. [2 p.]. Contact: Available from Myasthenia Gravis Foundation of America, Inc. 123 West Madison Street, Suite 800, Chicago, IL 60602. (800) 541-5454 or (312) 853-0522. Fax (312) 853-0523. E-mail: [email protected]. Website: www.myasthenia.org. PRICE: Single copy free. Summary: Myasthenia gravis (MG) is an autoimmune, neuromuscular disease that is characterized by varying weakness of voluntary muscle groups. Symptoms of MG may include drooping eyelids, double vision, slurred speech, nasal quality to voice, inability to speak, drooling, problems chewing or swallowing, trouble sitting up or holding the head erect or walking, weak cough, and shortness of breath. This brochure provides a guide to pre hospital care that may be used prior to the emergency management of MG. The brochure reviews the primary treatment objectives: maintain airway, support respirations, and transport immediately. A medical emergency may arise when respiratory muscles become so weak that respirations are shallow and ineffective, or the airway becomes obstructed due to weakened posterior pharyngeal muscles and accumulated secretions. The brochure includes two charts summarizing the assessment and treatment guidelines for severe difficulty breathing and for severe difficulty

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swallowing. The brochure also outlines general treatment guidelines and precautions, and lists other subjective or objective symptoms related to MG or to the medications used to treat MG. The National Guideline Clearinghouse™ The National Guideline Clearinghouse™ offers hundreds of evidence-based clinical practice guidelines published in the United States and other countries. You can search this site located at http://www.guideline.gov/ by using the keyword “myasthenia gravis” (or synonyms). The following was recently posted: •

Practice parameter for repetitive nerve stimulation and single fiber EMG evaluation of adults with suspected myasthenia gravis or Lambert-Eaton myasthenic syndrome: summary statement Source: American Association of Electrodiagnostic Medicine - Medical Specialty Society; 2001 September; 3 pages http://www.guideline.gov/summary/summary.aspx?doc_id=3347&nbr=2573&a mp;string=myasthenia+AND+gravis

•

Practice parameter: thymectomy for autoimmune myasthenia gravis (an evidencebased review). Report of the Quality Standards Subcommittee of the American Academy of Neurology Source: American Academy of Neurology - Medical Specialty Society; 2000 July; 9 pages http://www.guideline.gov/summary/summary.aspx?doc_id=2826&nbr=2052&a mp;string=myasthenia+AND+gravis 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: •

Myasthenia Gravis Summary: A general overview of myasthenia gravis that includes a description of the disorder, and treatment, prognosis and research information. Source: National Institute of Neurological Disorders and Stroke, National Institutes of Health http://www.healthfinder.gov/scripts/recordpass.asp?RecordType=0&RecordID=1338 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 myasthenia gravis. The drawbacks of this approach are that the information


is not organized by theme and that the references are often a mix of information for professionals and patients. Nevertheless, a large number of the listed Web sites provide useful background information. We can only recommend this route, therefore, for relatively rare or specific disorders, or when using highly targeted searches. To use the NIH search utility, visit the following Web page: http://search.nih.gov/index.html. Additional Web Sources A number of Web sites are available to the public that often link to government sites. These can also point you in the direction of essential information. The following is a representative sample: •


•

Family Village: http://www.familyvillage.wisc.edu/specific.htm

•

Google: http://directory.google.com/Top/Health/Conditions_and_Diseases/

•

Med Help International: http://www.medhelp.org/HealthTopics/A.html

•

Open Directory Project: http://dmoz.org/Health/Conditions_and_Diseases/

•

Yahoo.com: http://dir.yahoo.com/Health/Diseases_and_Conditions/

•

WebMDHealth: http://my.webmd.com/health_topics

Associations and Myasthenia Gravis The following is a list of associations that provide information on and resources relating to myasthenia gravis: •

Myasthenia Gravis Association (UK) Telephone: 01332-290219 Toll-free: 0800-919922 Fax: 01332-293641 Email: [email protected] Web Site: www.mgauk.org.uk Background: The Myasthenia Gravis Association (MGA) is a not-for-profit organization in the United Kingdom that is dedicated to promoting the welfare of individuals affected by myasthenia gravis, an autoimmune disorder in which the body's immune system attacks and damages nerve signal receptor areas in muscles, causing muscle weakness and fatigue. Although the disease may affect any muscle of the body, muscles of the eyes, lips, tongue, throat, and neck are often affected. The Myasthenia Gravis Association was established in 1968 and currently includes approximately 62 branches (and another 5 on the way) throughout the United Kingdom and the Republic of Ireland. The Association is committed to offering information and support to affected individuals and family members, promoting public and professional awareness, and raising funds for research to improve diagnosis and treatment of the disease and, ultimately, to find a cure. The MGA also publishes a quarterly newsletter entitled the 'MGA News' and maintains a web site on the Internet. The Association's web site provides information on MGA-supported research; summaries of medical meetings, conferences, and scientific sessions; understandable information on myasthenia gravis; and links to additional sources of information and support.

Patient Resources

•

159

Myasthenia Gravis Foundation of America Telephone: (952) 545-9438 Toll-free: (800) 541-5454 Fax: (952) 646-2028 Email: [email protected] Web Site: http://www.myasthenia.org Background: The Myasthenia Gravis Foundation of America is a national not-for-profit agency dedicated to assisting people with myasthenia gravis through programs of research, education, information, and patient services. The foundation supports funding for medical research and promotes public awareness of myasthenia gravis. Myasthenia gravis is a rare autoimmune disease affecting the neuromuscular junction and producing weakness of voluntary muscles. The foundation also disseminates educational materials to those affected by this disease, their families, medical professionals, and the interested public. Organizational activities conducted by the foundation include support groups and patient advocacy. The Myasthenia Gravis Foundation produces national and chapter newsletters, numerous brochures and pamphlets, a Survival Guide, health alert cards, and manuals for nurses and physicians. Founded in 1952, the Myasthenia Gravis Foundation has more than 36 chapters and 100 support groups. Relevant area(s) of interest: Myasthenia Gravis

Finding Associations There are several Internet directories that provide lists of medical associations with information on or resources relating to myasthenia gravis. By consulting all of associations listed in this chapter, you will have nearly exhausted all sources for patient associations concerned with myasthenia gravis. 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 myasthenia gravis. 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 “myasthenia gravis” (or a synonym), and you will receive information on all relevant organizations listed in the database. Health Hotlines directs you to toll-free numbers to over 300 organizations. You can access this database directly at http://www.sis.nlm.nih.gov/hotlines/. On this page, you are given the option to search by keyword or by browsing the subject list. When you have received your search results, click on the name of the organization for its description and contact information. The Combined Health Information Database Another comprehensive source of information on healthcare associations is the Combined Health Information Database. Using the “Detailed Search” option, you will need to limit your search to “Organizations” and “myasthenia gravis”. 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 “myasthenia gravis” (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 “myasthenia gravis” (or a synonym) into the search box, and click “Submit Query.”

161

APPENDIX C. FINDING MEDICAL LIBRARIES Overview In this Appendix, we show you how to quickly find a medical library in your area.

Preparation Your local public library and medical libraries have interlibrary loan programs with the National Library of Medicine (NLM), one of the largest medical collections in the world. According to the NLM, most of the literature in the general and historical collections of the National Library of Medicine is available on interlibrary loan to any library. If you would like to access NLM medical literature, then visit a library in your area that can request the publications for you.26

Finding a Local Medical Library The quickest method to locate medical libraries is to use the Internet-based directory published by the National Network of Libraries of Medicine (NN/LM). This network includes 4626 members and affiliates that provide many services to librarians, health professionals, and the public. To find a library in your area, simply visit http://nnlm.gov/members/adv.html or call 1-800-338-7657.

Medical Libraries in the U.S. and Canada In addition to the NN/LM, the National Library of Medicine (NLM) lists a number of libraries with reference facilities that are open to the public. The following is the NLM’s list and includes hyperlinks to each library’s Web site. These Web pages can provide information on hours of operation and other restrictions. The list below is a small sample of

26

Adapted from the NLM: http://www.nlm.nih.gov/psd/cas/interlibrary.html.


libraries recommended by the National Library of Medicine (sorted alphabetically by name of the U.S. state or Canadian province where the library is located)27: •

Alabama: Health InfoNet of Jefferson County (Jefferson County Library Cooperative, Lister Hill Library of the Health Sciences), http://www.uab.edu/infonet/

•

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

•

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

•

California: Consumer Health Program and Services (CHIPS) (County of Los Angeles Public Library, Los Angeles County Harbor-UCLA Medical Center Library) - Carson, CA, http://www.colapublib.org/services/chips.html

•

California: Gateway Health Library (Sutter Gould Medical Foundation)

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California: Health Library (Stanford University Medical Center), http://wwwmed.stanford.edu/healthlibrary/

•

California: Patient Education Resource Center - Health Information and Resources (University of California, San Francisco), http://sfghdean.ucsf.edu/barnett/PERC/default.asp

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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/

•

California: Health Sciences Libraries (University of California, Davis), http://www.lib.ucdavis.edu/healthsci/

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California: ValleyCare Health Library & Ryan Comer Cancer Resource Center (ValleyCare Health System, Pleasanton), http://gaelnet.stmarysca.edu/other.libs/gbal/east/vchl.html

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California: Washington Community Health Resource Library (Fremont), http://www.healthlibrary.org/

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Colorado: William V. Gervasini Memorial Library (Exempla Healthcare), http://www.saintjosephdenver.org/yourhealth/libraries/

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Connecticut: Hartford Hospital Health Science Libraries (Hartford Hospital), http://www.harthosp.org/library/

•

Connecticut: Healthnet: Connecticut Consumer Health Information Center (University of Connecticut Health Center, Lyman Maynard Stowe Library), http://library.uchc.edu/departm/hnet/

27

Abstracted from http://www.nlm.nih.gov/medlineplus/libraries.html.

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•

Connecticut: Waterbury Hospital Health Center Library (Waterbury Hospital, Waterbury), http://www.waterburyhospital.com/library/consumer.shtml

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Delaware: Consumer Health Library (Christiana Care Health System, Eugene du Pont Preventive Medicine & Rehabilitation Institute, Wilmington), http://www.christianacare.org/health_guide/health_guide_pmri_health_info.cfm

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Delaware: Lewis B. Flinn Library (Delaware Academy of Medicine, Wilmington), http://www.delamed.org/chls.html

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Georgia: Family Resource Library (Medical College of Georgia, Augusta), http://cmc.mcg.edu/kids_families/fam_resources/fam_res_lib/frl.htm

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Georgia: Health Resource Center (Medical Center of Central Georgia, Macon), http://www.mccg.org/hrc/hrchome.asp

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Hawaii: Hawaii Medical Library: Consumer Health Information Service (Hawaii Medical Library, Honolulu), http://hml.org/CHIS/

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Idaho: DeArmond Consumer Health Library (Kootenai Medical Center, Coeur d’Alene), http://www.nicon.org/DeArmond/index.htm

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Illinois: Health Learning Center of Northwestern Memorial Hospital (Chicago), http://www.nmh.org/health_info/hlc.html

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Illinois: Medical Library (OSF Saint Francis Medical Center, Peoria), http://www.osfsaintfrancis.org/general/library/

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Kentucky: Medical Library - Services for Patients, Families, Students & the Public (Central Baptist Hospital, Lexington), http://www.centralbap.com/education/community/library.cfm

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Kentucky: University of Kentucky - Health Information Library (Chandler Medical Center, Lexington), http://www.mc.uky.edu/PatientEd/

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Louisiana: Alton Ochsner Medical Foundation Library (Alton Ochsner Medical Foundation, New Orleans), http://www.ochsner.org/library/

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Louisiana: Louisiana State University Health Sciences Center Medical LibraryShreveport, http://lib-sh.lsuhsc.edu/

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Maine: Franklin Memorial Hospital Medical Library (Franklin Memorial Hospital, Farmington), http://www.fchn.org/fmh/lib.htm

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Maine: Gerrish-True Health Sciences Library (Central Maine Medical Center, Lewiston), http://www.cmmc.org/library/library.html

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Maine: Hadley Parrot Health Science Library (Eastern Maine Healthcare, Bangor), http://www.emh.org/hll/hpl/guide.htm

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Maine: Maine Medical Center Library (Maine Medical Center, Portland), http://www.mmc.org/library/

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Maine: Parkview Hospital (Brunswick), http://www.parkviewhospital.org/

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Maine: Southern Maine Medical Center Health Sciences Library (Southern Maine Medical Center, Biddeford), http://www.smmc.org/services/service.php3?choice=10

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Maine: Stephens Memorial Hospital’s Health Information Library (Western Maine Health, Norway), http://www.wmhcc.org/Library/


•

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/

•

Massachusetts: Treadwell Library Consumer Health Reference Center (Massachusetts General Hospital), http://www.mgh.harvard.edu/library/chrcindex.html

•

Massachusetts: UMass HealthNet (University of Massachusetts Medical School, Worchester), http://healthnet.umassmed.edu/

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Michigan: Botsford General Hospital Library - Consumer Health (Botsford General Hospital, Library & Internet Services), http://www.botsfordlibrary.org/consumer.htm

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Michigan: Helen DeRoy Medical Library (Providence Hospital and Medical Centers), http://www.providence-hospital.org/library/

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Michigan: Marquette General Hospital - Consumer Health Library (Marquette General Hospital, Health Information Center), http://www.mgh.org/center.html

•

Michigan: Patient Education Resouce Center - University of Michigan Cancer Center (University of Michigan Comprehensive Cancer Center, Ann Arbor), http://www.cancer.med.umich.edu/learn/leares.htm

•

Michigan: Sladen Library & Center for Health Information Resources - Consumer Health Information (Detroit), http://www.henryford.com/body.cfm?id=39330

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Montana: Center for Health Information (St. Patrick Hospital and Health Sciences Center, Missoula)

•

National: Consumer Health Library Directory (Medical Library Association, Consumer and Patient Health Information Section), http://caphis.mlanet.org/directory/index.html

•

National: National Network of Libraries of Medicine (National Library of Medicine) provides library services for health professionals in the United States who do not have access to a medical library, http://nnlm.gov/

•

National: NN/LM List of Libraries Serving the Public (National Network of Libraries of Medicine), http://nnlm.gov/members/

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Nevada: Health Science Library, West Charleston Library (Las Vegas-Clark County Library District, Las Vegas), http://www.lvccld.org/special_collections/medical/index.htm

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New Hampshire: Dartmouth Biomedical Libraries (Dartmouth College Library, Hanover), http://www.dartmouth.edu/~biomed/resources.htmld/conshealth.htmld/

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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

•

New Jersey: Meland Foundation (Englewood Hospital and Medical Center, Englewood), http://www.geocities.com/ResearchTriangle/9360/

•

New York: Choices in Health Information (New York Public Library) - NLM Consumer Pilot Project participant, http://www.nypl.org/branch/health/links.html

•

New York: Health Information Center (Upstate Medical University, State University of New York, Syracuse), http://www.upstate.edu/library/hic/

•

New York: Health Sciences Library (Long Island Jewish Medical Center, New Hyde Park), http://www.lij.edu/library/library.html

•

New York: ViaHealth Medical Library (Rochester General Hospital), http://www.nyam.org/library/

•

Ohio: Consumer Health Library (Akron General Medical Center, Medical & Consumer Health Library), http://www.akrongeneral.org/hwlibrary.htm

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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/

•

Pennsylvania: Community Health Information Library (Milton S. Hershey Medical Center, Hershey), http://www.hmc.psu.edu/commhealth/

•

Pennsylvania: Community Health Resource Library (Geisinger Medical Center, Danville), http://www.geisinger.edu/education/commlib.shtml

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Pennsylvania: HealthInfo Library (Moses Taylor Hospital, Scranton), http://www.mth.org/healthwellness.html

•

Pennsylvania: Hopwood Library (University of Pittsburgh, Health Sciences Library System, Pittsburgh), http://www.hsls.pitt.edu/guides/chi/hopwood/index_html

•

Pennsylvania: Koop Community Health Information Center (College of Physicians of Philadelphia), http://www.collphyphil.org/kooppg1.shtml

•

Pennsylvania: Learning Resources Center - Medical Library (Susquehanna Health System, Williamsport), http://www.shscares.org/services/lrc/index.asp

•

Pennsylvania: Medical Library (UPMC Health System, Pittsburgh), http://www.upmc.edu/passavant/library.htm

•

Quebec, Canada: Medical Library (Montreal General Hospital), http://www.mghlib.mcgill.ca/


•

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

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On-line Medical Dictionary (CancerWEB): http://cancerweb.ncl.ac.uk/omd/

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Rare Diseases Terms (Office of Rare Diseases): http://ord.aspensys.com/asp/diseases/diseases.asp

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Technology Glossary (National Library of Medicine) - Health Care Technology: http://www.nlm.nih.gov/nichsr/ta101/ta10108.htm

Beyond these, MEDLINEplus contains a very patient-friendly encyclopedia covering every aspect of medicine (licensed from A.D.A.M., Inc.). The ADAM Medical Encyclopedia can be accessed at http://www.nlm.nih.gov/medlineplus/encyclopedia.html. ADAM is also available on commercial Web sites such as drkoop.com (http://www.drkoop.com/) and Web MD (http://my.webmd.com/adam/asset/adam_disease_articles/a_to_z/a). The NIH suggests the following Web sites in the ADAM Medical Encyclopedia when searching for information on myasthenia gravis: •

Basic Guidelines for Myasthenia Gravis Myasthenia gravis Web site: http://www.nlm.nih.gov/medlineplus/ency/article/000712.htm Myasthenia gravis - resources Web site: http://www.nlm.nih.gov/medlineplus/ency/article/002156.htm

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Signs & Symptoms for Myasthenia Gravis Breathing difficulty Web site: http://www.nlm.nih.gov/medlineplus/ency/article/003075.htm Difficulty talking Web site: http://www.nlm.nih.gov/medlineplus/ency/article/003204.htm Double vision Web site: http://www.nlm.nih.gov/medlineplus/ency/article/003029.htm


Drooling Web site: http://www.nlm.nih.gov/medlineplus/ency/article/003048.htm Dysarthria Web site: http://www.nlm.nih.gov/medlineplus/ency/article/003204.htm Dysphagia Web site: http://www.nlm.nih.gov/medlineplus/ency/article/003115.htm Dysphonia Web site: http://www.nlm.nih.gov/medlineplus/ency/article/003054.htm Eyelid drooping Web site: http://www.nlm.nih.gov/medlineplus/ency/article/003035.htm Facial paralysis Web site: http://www.nlm.nih.gov/medlineplus/ency/article/003028.htm Fatigue Web site: http://www.nlm.nih.gov/medlineplus/ency/article/003088.htm Hoarseness or changing voice Web site: http://www.nlm.nih.gov/medlineplus/ency/article/003054.htm Muscle Web site: http://www.nlm.nih.gov/medlineplus/ency/article/003193.htm Muscle atrophy Web site: http://www.nlm.nih.gov/medlineplus/ency/article/003188.htm Muscle weakness Web site: http://www.nlm.nih.gov/medlineplus/ency/article/003174.htm Paralysis Web site: http://www.nlm.nih.gov/medlineplus/ency/article/003190.htm Respiratory arrest Web site: http://www.nlm.nih.gov/medlineplus/ency/article/003069.htm Stress Web site: http://www.nlm.nih.gov/medlineplus/ency/article/003211.htm Swallowing difficulty Web site: http://www.nlm.nih.gov/medlineplus/ency/article/003115.htm Weakness Web site: http://www.nlm.nih.gov/medlineplus/ency/article/003174.htm •

Diagnostics and Tests for Myasthenia Gravis Acetylcholine receptor antibodies Web site: http://www.nlm.nih.gov/medlineplus/ency/article/003576.htm

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AMP Web site: http://www.nlm.nih.gov/medlineplus/ency/article/003368.htm ANA Web site: http://www.nlm.nih.gov/medlineplus/ency/article/003535.htm Antibody titer Web site: http://www.nlm.nih.gov/medlineplus/ency/article/003333.htm Complement Web site: http://www.nlm.nih.gov/medlineplus/ency/article/003456.htm Contraction Web site: http://www.nlm.nih.gov/medlineplus/ency/article/003405.htm CT Web site: http://www.nlm.nih.gov/medlineplus/ency/article/003330.htm Electromyography Web site: http://www.nlm.nih.gov/medlineplus/ency/article/003929.htm EMG Web site: http://www.nlm.nih.gov/medlineplus/ency/article/003929.htm Nerve conduction studies Web site: http://www.nlm.nih.gov/medlineplus/ency/article/003927.htm Nerve conduction velocity Web site: http://www.nlm.nih.gov/medlineplus/ency/article/003927.htm RF Web site: http://www.nlm.nih.gov/medlineplus/ency/article/003548.htm T4 Web site: http://www.nlm.nih.gov/medlineplus/ency/article/003517.htm Tensilon test Web site: http://www.nlm.nih.gov/medlineplus/ency/article/003930.htm Thyroid function tests Web site: http://www.nlm.nih.gov/medlineplus/ency/article/003444.htm TSH Web site: http://www.nlm.nih.gov/medlineplus/ency/article/003684.htm •

Nutrition for Myasthenia Gravis Vitamin B12 Web site: http://www.nlm.nih.gov/medlineplus/ency/article/002403.htm


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Surgery and Procedures for Myasthenia Gravis Tracheostomy Web site: http://www.nlm.nih.gov/medlineplus/ency/article/002955.htm

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Background Topics for Myasthenia Gravis Antibodies Web site: http://www.nlm.nih.gov/medlineplus/ency/article/002223.htm Autosomal recessive Web site: http://www.nlm.nih.gov/medlineplus/ency/article/002052.htm Choking Web site: http://www.nlm.nih.gov/medlineplus/ency/article/000047.htm Chronic Web site: http://www.nlm.nih.gov/medlineplus/ency/article/002312.htm Enzyme Web site: http://www.nlm.nih.gov/medlineplus/ency/article/002353.htm Immune response Web site: http://www.nlm.nih.gov/medlineplus/ency/article/000821.htm Incidence Web site: http://www.nlm.nih.gov/medlineplus/ency/article/002387.htm Inheritance Web site: http://www.nlm.nih.gov/medlineplus/ency/article/002048.htm Intravenous Web site: http://www.nlm.nih.gov/medlineplus/ency/article/002383.htm Myasthenia gravis - support group Web site: http://www.nlm.nih.gov/medlineplus/ency/article/002156.htm Physical examination Web site: http://www.nlm.nih.gov/medlineplus/ency/article/002274.htm Symptomatic Web site: http://www.nlm.nih.gov/medlineplus/ency/article/002293.htm

Online Dictionary Directories The following are additional online directories compiled by the National Library of Medicine, including a number of specialized medical dictionaries: •

Medical Dictionaries: Medical & Biological (World Health Organization): http://www.who.int/hlt/virtuallibrary/English/diction.htm#Medical

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•

MEL-Michigan Electronic Library List of Online Health and Medical Dictionaries (Michigan Electronic Library): http://mel.lib.mi.us/health/health-dictionaries.html

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Patient Education: Glossaries (DMOZ Open Directory Project): http://dmoz.org/Health/Education/Patient_Education/Glossaries/

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Web of Online Dictionaries (Bucknell University): http://www.yourdictionary.com/diction5.html#medicine

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MYASTHENIA GRAVIS DICTIONARY The definitions below are derived from official public sources, including the National Institutes of Health [NIH] and the European Union [EU]. 3-dimensional: 3-D. A graphic display of depth, width, and height. Three-dimensional radiation therapy uses computers to create a 3-dimensional picture of the tumor. This allows doctors to give the highest possible dose of radiation to the tumor, while sparing the normal tissue as much as possible. [NIH] Abdomen: That portion of the body that lies between the thorax and the pelvis. [NIH] Abdominal: Having to do with the abdomen, which is the part of the body between the chest and the hips that contains the pancreas, stomach, intestines, liver, gallbladder, and other organs. [NIH] Abducens: A striated, extrinsic muscle of the eyeball that originates from the annulus of Zinn. [NIH] Abducens Nerve: The 6th cranial nerve. The abducens nerve originates in the abducens nucleus of the pons and sends motor fibers to the lateral rectus muscles of the eye. Damage to the nerve or its nucleus disrupts horizontal eye movement control. [NIH] Abducens Nerve Diseases: Diseases of the sixth cranial (abducens) nerve or its nucleus in the pons. The nerve may be injured along its course in the pons, intracranially as it travels along the base of the brain, in the cavernous sinus, or at the level of superior orbital fissure or orbit. Dysfunction of the nerve causes lateral rectus muscle weakness, resulting in horizontal diplopia that is maximal when the affected eye is abducted and esotropia. Common conditions associated with nerve injury include intracranial hypertension; craniocerebral trauma; ischemia; and infratentorial neoplasms. [NIH] Abductor: A muscle that draws a part away from the median line. [NIH] Aberrant: Wandering or deviating from the usual or normal course. [EU] Acantholysis: Separation of the prickle cells of the stratum spinosum of the epidermis, resulting in atrophy of the prickle cell layer. It is seen in diseases such as pemphigus vulgaris (see pemphigus) and keratosis follicularis. [NIH] Accommodation: Adjustment, especially that of the eye for various distances. [EU] 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] Acetylcholinesterase: An enzyme that catalyzes the hydrolysis of acetylcholine to choline and acetate. In the CNS, this enzyme plays a role in the function of peripheral neuromuscular junctions. EC 3.1.1.7. [NIH] Actin: Essential component of the cell skeleton. [NIH] Actinin: A protein factor that regulates the length of R-actin. It is chemically similar, but immunochemically distinguishable from actin. [NIH] Action Potentials: The electric response of a nerve or muscle to its stimulation. [NIH] Acute renal: A condition in which the kidneys suddenly stop working. In most cases, kidneys can recover from almost complete loss of function. [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] Adjuvant: A substance which aids another, such as an auxiliary remedy; in immunology, nonspecific stimulator (e.g., BCG vaccine) of the immune response. [EU] Adoptive Transfer: Form of passive immunization where previously sensitized immunologic agents (cells or serum) are transferred to non-immune recipients. When transfer of cells is used as a therapy for the treatment of neoplasms, it is called adoptive immunotherapy (immunotherapy, adoptive). [NIH] Adrenal Cortex: The outer layer of the adrenal gland. It secretes mineralocorticoids, androgens, and glucocorticoids. [NIH] Adrenaline: A hormone. Also called epinephrine. [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] Adrenoreceptor: Receptors specifically sensitive to and operated by adrenaline and/or noradrenaline and related sympathomimetic drugs. Adrenoreceptor is an alternative name. [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] 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.

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[NIH]

Agonist: In anatomy, a prime mover. In pharmacology, a drug that has affinity for and stimulates physiologic activity at cell receptors normally stimulated by naturally occurring substances. [EU] 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] Airway: A device for securing unobstructed passage of air into and out of the lungs during general anesthesia. [NIH] Albumin: 1. Any protein that is soluble in water and moderately concentrated salt solutions and is coagulable by heat. 2. Serum albumin; the major plasma protein (approximately 60 per cent of the total), which is responsible for much of the plasma colloidal osmotic pressure and serves as a transport protein carrying large organic anions, such as fatty acids, bilirubin, and many drugs, and also carrying certain hormones, such as cortisol and thyroxine, when their specific binding globulins are saturated. Albumin is synthesized in the liver. Low serum levels occur in protein malnutrition, active inflammation and serious hepatic and renal disease. [EU] Alexia: The inability to recognize or comprehend written or printed words. [NIH] Algorithms: A procedure consisting of a sequence of algebraic formulas and/or logical steps to calculate or determine a given task. [NIH] Alkaline: Having the reactions of an alkali. [EU] Alkaloid: A member of a large group of chemicals that are made by plants and have nitrogen in them. Some alkaloids have been shown to work against cancer. [NIH] Allergen: An antigenic substance capable of producing immediate-type hypersensitivity (allergy). [EU] Allogeneic: Taken from different individuals of the same species. [NIH] Allogeneic bone marrow transplantation: A procedure in which a person receives stem cells, the cells from which all blood cells develop, from a compatible, though not genetically identical, donor. [NIH] Alopecia: Absence of hair from areas where it is normally present. [NIH] Alpha Particles: Positively charged particles composed of two protons and two neutrons, i.e., helium nuclei, emitted during disintegration of very heavy isotopes; a beam of alpha particles or an alpha ray has very strong ionizing power, but weak penetrability. [NIH] Alternative medicine: Practices not generally recognized by the medical community as standard or conventional medical approaches and used instead of standard treatments. Alternative medicine includes the taking of dietary supplements, megadose vitamins, and herbal preparations; the drinking of special teas; and practices such as massage therapy, magnet therapy, spiritual healing, and meditation. [NIH] Alternative Splicing: A process whereby multiple protein isoforms are generated from a single gene. Alternative splicing involves the splicing together of nonconsecutive exons during the processing of some, but not all, transcripts of the gene. Thus a particular exon may be connected to any one of several alternative exons to form messenger RNA. The alternative forms produce proteins in which one part is common while the other part is different. [NIH] Alveolar Process: The thickest and spongiest part of the maxilla and mandible hollowed out into deep cavities for the teeth. [NIH]


Ameliorated: A changeable condition which prevents the consequence of a failure or accident from becoming as bad as it otherwise would. [NIH] Amino Acid Sequence: The order of amino acids as they occur in a polypeptide chain. This is referred to as the primary structure of proteins. It is of fundamental importance in determining protein conformation. [NIH] Amino Acid Substitution: The naturally occurring or experimentally induced replacement of one or more amino acids in a protein with another. If a functionally equivalent amino acid is substituted, the protein may retain wild-type activity. Substitution may also diminish or eliminate protein function. Experimentally induced substitution is often used to study enzyme activities and binding site properties. [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] Amphetamines: Analogs or derivatives of amphetamine. Many are sympathomimetics and central nervous system stimulators causing excitation, vasopression, bronchodilation, and to varying degrees, anorexia, analepsis, nasal decongestion, and some smooth muscle relaxation. [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] Anaesthesia: Loss of feeling or sensation. Although the term is used for loss of tactile sensibility, or of any of the other senses, it is applied especially to loss of the sensation of pain, as it is induced to permit performance of surgery or other painful procedures. [EU] Analeptic: A drug which acts as a restorative, such as caffeine, amphetamine, pentylenetetrazol, etc. [EU] Analgesic: An agent that alleviates pain without causing loss of consciousness. [EU] Analog: In chemistry, a substance that is similar, but not identical, to another. [NIH] Analogous: Resembling or similar in some respects, as in function or appearance, but not in origin or development;. [EU] Anaphylatoxins: The family of peptides C3a, C4a, C5a, and C5a des-arginine produced in the serum during complement activation. They produce smooth muscle contraction, mast cell histamine release, affect platelet aggregation, and act as mediators of the local inflammatory process. The order of anaphylatoxin activity from strongest to weakest is C5a, C3a, C4a, and C5a des-arginine. The latter is the so-called "classical" anaphylatoxin but shows no spasmogenic activity though it contains some chemotactic ability. [NIH] 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] Anemia: A reduction in the number of circulating erythrocytes or in the quantity of hemoglobin. [NIH]

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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] Aneurism: A localized abnormal dilatation of a blood vessel filled with fluid or clotted blood, forming a pulsating tumor, and resulting from disease of the vessel wall. [NIH] Aneurysm: A sac formed by the dilatation of the wall of an artery, a vein, or the heart. [NIH] Angiogenesis: Blood vessel formation. Tumor angiogenesis is the growth of blood vessels from surrounding tissue to a solid tumor. This is caused by the release of chemicals by the tumor. [NIH] Angiopathy: Disease of the blood vessels (arteries, veins, and capillaries) that occurs when someone has diabetes for a long time. There are two types of angiopathy: macroangiopathy and microangiopathy. In macroangiopathy, fat and blood clots build up in the large blood vessels, stick to the vessel walls, and block the flow of blood. In microangiopathy, the walls of the smaller blood vessels become so thick and weak that they bleed, leak protein, and slow the flow of blood through the body. Then the cells, for example, the ones in the center of the eye, do not get enough blood and may be damaged. [NIH] Animal model: An animal with a disease either the same as or like a disease in humans. Animal models are used to study the development and progression of diseases and to test new treatments before they are given to humans. Animals with transplanted human cancers or other tissues are called xenograft models. [NIH] Anions: Negatively charged atoms, radicals or groups of atoms which travel to the anode or positive pole during electrolysis. [NIH] Anorexia: Lack or loss of appetite for food. Appetite is psychologic, dependent on memory and associations. Anorexia can be brought about by unattractive food, surroundings, or company. [NIH] Anterior Cerebral Artery: Artery formed by the bifurcation of the internal carotid artery. Branches of the anterior cerebral artery supply the caudate nucleus, internal capsule, putamen, septal nuclei, gyrus cinguli, and surfaces of the frontal lobe and parietal lobe. [NIH] Anthelmintic: An agent that is destructive to worms. [EU] Antiallergic: Counteracting allergy or allergic conditions. [EU] Antibacterial: A substance that destroys bacteria or suppresses their growth or reproduction. [EU] Antibiotic: A drug used to treat infections caused by bacteria and other microorganisms. [NIH]

Antibodies: Immunoglobulin molecules having a specific amino acid sequence by virtue of which they interact only with the antigen that induced their synthesis in cells of the lymphoid series (especially plasma cells), or with an antigen closely related to it. [NIH] Antibody: A type of protein made by certain white blood cells in response to a foreign substance (antigen). Each antibody can bind to only a specific antigen. The purpose of this binding is to help destroy the antigen. Antibodies can work in several ways, depending on the nature of the antigen. Some antibodies destroy antigens directly. Others make it easier for white blood cells to destroy the antigen. [NIH] 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]


Antidote: A remedy for counteracting a poison. [EU] Antiepileptic: An agent that combats epilepsy. [EU] Antifungal: Destructive to fungi, or suppressing their reproduction or growth; effective against fungal infections. [EU] Antigen: Any substance which is capable, under appropriate conditions, of inducing a specific immune response and of reacting with the products of that response, that is, with specific antibody or specifically sensitized T-lymphocytes, or both. Antigens may be soluble substances, such as toxins and foreign proteins, or particulate, such as bacteria and tissue cells; however, only the portion of the protein or polysaccharide molecule known as the antigenic determinant (q.v.) combines with antibody or a specific receptor on a lymphocyte. Abbreviated Ag. [EU] Antigen-Antibody Complex: The complex formed by the binding of antigen and antibody molecules. The deposition of large antigen-antibody complexes leading to tissue damage causes immune complex diseases. [NIH] Antigen-presenting cell: APC. A cell that shows antigen on its surface to other cells of the immune system. This is an important part of an immune response. [NIH] Anti-inflammatory: Having to do with reducing inflammation. [NIH] Anti-Inflammatory Agents: Substances that reduce or suppress inflammation. [NIH] Antimetabolite: A chemical that is very similar to one required in a normal biochemical reaction in cells. Antimetabolites can stop or slow down the reaction. [NIH] Antineoplastic: Inhibiting or preventing the development of neoplasms, checking the maturation and proliferation of malignant cells. [EU] Antiserum: The blood serum obtained from an animal after it has been immunized with a particular antigen. It will contain antibodies which are specific for that antigen as well as antibodies specific for any other antigen with which the animal has previously been immunized. [NIH] 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 Aneurysm: Aneurysm of the aorta. [NIH] Apathy: Lack of feeling or emotion; indifference. [EU] Aphasia: A cognitive disorder marked by an impaired ability to comprehend or express language in its written or spoken form. This condition is caused by diseases which affect the language areas of the dominant hemisphere. Clinical features are used to classify the various subtypes of this condition. General categories include receptive, expressive, and mixed forms of aphasia. [NIH] Aplasia: Lack of development of an organ or tissue, or of the cellular products from an organ or tissue. [EU] Aplastic anemia: A condition in which the bone marrow is unable to produce blood cells. [NIH]

Apnea: A transient absence of spontaneous respiration. [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

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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] Apraxia: Loss of ability to perform purposeful movements, in the absence of paralysis or sensory disturbance, caused by lesions in the cortex. [NIH] Arginine: An essential amino acid that is physiologically active in the L-form. [NIH] Aromatic: Having a spicy odour. [EU] Arrhythmia: Any variation from the normal rhythm or rate of the heart beat. [NIH] Arterial: Pertaining to an artery or to the arteries. [EU] Arteries: The vessels carrying blood away from the heart. [NIH] Articular: Of or pertaining to a joint. [EU] Articulation: The relationship of two bodies by means of a moveable joint. [NIH] Arytenoid Cartilage: One of a pair of small pyramidal cartilages that articulate with the lamina of the cricoid cartilage. The corresponding vocal ligament and several muscles are attached to it. [NIH] Aspiration: The act of inhaling. [NIH] Assay: Determination of the amount of a particular constituent of a mixture, or of the biological or pharmacological potency of a drug. [EU] Astringents: Agents, usually topical, that cause the contraction of tissues for the control of bleeding or secretions. [NIH] 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] 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] Attenuated: Strain with weakened or reduced virulence. [NIH] Auditory: Pertaining to the sense of hearing. [EU] Autoantibodies: Antibodies that react with self-antigens (autoantigens) of the organism that produced them. [NIH] Autoantigens: Endogenous tissue constituents that have the ability to interact with autoantibodies and cause an immune response. [NIH] Autoimmune disease: A condition in which the body recognizes its own tissues as foreign and directs an immune response against them. [NIH] Autoimmunity: Process whereby the immune system reacts against the body's own tissues. Autoimmunity may produce or be caused by autoimmune diseases. [NIH] 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] Autonomic Neuropathy: A disease of the nerves affecting mostly the internal organs such as the bladder muscles, the cardiovascular system, the digestive tract, and the genital organs. These nerves are not under a person's conscious control and function automatically. Also called visceral neuropathy. [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] 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] 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] Barium: An element of the alkaline earth group of metals. It has an atomic symbol Ba, atomic number 56, and atomic weight 138. All of its acid-soluble salts are poisonous. [NIH] Barium swallow: A series of x-rays of the esophagus. The x-ray pictures are taken after the person drinks a solution that contains barium. The barium coats and outlines the esophagus on the x-ray. Also called an esophagram. [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]

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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]

Benzene: Toxic, volatile, flammable liquid hydrocarbon biproduct of coal distillation. It is used as an industrial solvent in paints, varnishes, lacquer thinners, gasoline, etc. Benzene causes central nervous system damage acutely and bone marrow damage chronically and is carcinogenic. It was formerly used as parasiticide. [NIH] Beta-Galactosidase: A group of enzymes that catalyzes the hydrolysis of terminal, nonreducing beta-D-galactose residues in beta-galactosides. Deficiency of beta-Galactosidase A1 may cause gangliodisosis GM1. EC 3.2.1.23. [NIH] Beta-pleated: Particular three-dimensional pattern of amyloidoses. [NIH] Bifida: A defect in development of the vertebral column in which there is a central deficiency of the vertebral lamina. [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 Ducts: Tubes that carry bile from the liver to the gallbladder for storage and to the small intestine for use in digestion. [NIH] Bilirubin: A bile pigment that is a degradation product of heme. [NIH] Binding Sites: The reactive parts of a macromolecule that directly participate in its specific combination with another molecule. [NIH] Bioassay: Determination of the relative effective strength of a substance (as a vitamin, hormone, or drug) by comparing its effect on a test organism with that of a standard preparation. [NIH] Biochemical: Relating to biochemistry; characterized by, produced by, or involving chemical reactions in living organisms. [EU] Biochemical Phenomena: Biochemical functions, activities, and processes at organic and molecular levels in humans, animals, microorganisms, and plants. [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] 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] Bipolar Disorder: A major affective disorder marked by severe mood swings (manic or major depressive episodes) and a tendency to remission and recurrence. [NIH] Bladder: The organ that stores urine. [NIH] Blastocyst: The mammalian embryo in the post-morula stage in which a fluid-filled cavity, enclosed primarily by trophoblast, contains an inner cell mass which becomes the embryonic disc. [NIH] Blasts: Immature blood cells. [NIH] Blepharoptosis: Drooping of the upper lid due to deficient development or paralysis of the levator palpebrae muscle. [NIH] Blister: Visible accumulations of fluid within or beneath the epidermis. [NIH] Blood Cell Count: A count of the number of leukocytes and erythrocytes per unit volume in a sample of venous blood. A complete blood count (CBC) also includes measurement of the hemoglobin, hematocrit, and erythrocyte indices. [NIH] Blood Coagulation: The process of the interaction of blood coagulation factors that results in an insoluble fibrin clot. [NIH] Blood Glucose: Glucose in blood. [NIH] Blood Platelets: Non-nucleated disk-shaped cells formed in the megakaryocyte and found in the blood of all mammals. They are mainly involved in blood coagulation. [NIH] Blood pressure: The pressure of blood against the walls of a blood vessel or heart chamber. Unless there is reference to another location, such as the pulmonary artery or one of the heart chambers, it refers to the pressure in the systemic arteries, as measured, for example, in the forearm. [NIH] Blood vessel: A tube in the body through which blood circulates. Blood vessels include a network of arteries, arterioles, capillaries, venules, and veins. [NIH] Blood-Brain Barrier: Specialized non-fenestrated tightly-joined endothelial cells (tight junctions) that form a transport barrier for certain substances between the cerebral capillaries and the brain tissue. [NIH] Bone Marrow: The soft tissue filling the cavities of bones. Bone marrow exists in two types, yellow and red. Yellow marrow is found in the large cavities of large bones and consists mostly of fat cells and a few primitive blood cells. Red marrow is a hematopoietic tissue and is the site of production of erythrocytes and granular leukocytes. Bone marrow is made up of a framework of connective tissue containing branching fibers with the frame being filled with marrow cells. [NIH] Bone Marrow Transplantation: The transference of bone marrow from one human or animal to another. [NIH] 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] Brain Diseases: Pathologic conditions affecting the brain, which is composed of the

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intracranial components of the central nervous system. This includes (but is not limited to) the cerebral cortex; intracranial white matter; basal ganglia; thalamus; hypothalamus; brain stem; and cerebellum. [NIH] Brain Neoplasms: Neoplasms of the intracranial components of the central nervous system, including the cerebral hemispheres, basal ganglia, hypothalamus, thalamus, brain stem, and cerebellum. Brain neoplasms are subdivided into primary (originating from brain tissue) and secondary (i.e., metastatic) forms. Primary neoplasms are subdivided into benign and malignant forms. In general, brain tumors may also be classified by age of onset, histologic type, or presenting location in the brain. [NIH] Brain Stem: The part of the brain that connects the cerebral hemispheres with the spinal cord. It consists of the mesencephalon, pons, and medulla oblongata. [NIH] Branch: Most commonly used for branches of nerves, but applied also to other structures. [NIH]

Broad-spectrum: Effective against a wide range of microorganisms; said of an antibiotic. [EU] Buccal: Pertaining to or directed toward the cheek. In dental anatomy, used to refer to the buccal surface of a tooth. [EU] Bulbar: Pertaining to a bulb; pertaining to or involving the medulla oblongata, as bulbar paralysis. [EU] Burns: Injuries to tissues caused by contact with heat, steam, chemicals (burns, chemical), electricity (burns, electric), or the like. [NIH] Burns, Electric: Burns produced by contact with electric current or from a sudden discharge of electricity. [NIH] Butyric Acid: A four carbon acid, CH3CH2CH2COOH, with an unpleasant odor that occurs in butter and animal fat as the glycerol ester. [NIH] Butyrylcholinesterase: An aspect of cholinesterase (EC 3.1.1.8). [NIH] Caesarean section: A surgical incision through the abdominal and uterine walls in order to deliver a baby. [NIH] Calcitonin Gene-Related Peptide: Calcitonin gene-related peptide. A 37-amino acid peptide derived from the calcitonin gene. It occurs as a result of alternative processing of mRNA from the calcitonin gene. The neuropeptide is widely distributed in neural tissue of the brain, gut, perivascular nerves, and other tissue. The peptide produces multiple biological effects and has both circulatory and neurotransmitter modes of action. In particular, it is a potent endogenous vasodilator. [NIH] Calcium: A basic element found in nearly all organized tissues. It is a member of the alkaline earth family of metals with the atomic symbol Ca, atomic number 20, and atomic weight 40. Calcium is the most abundant mineral in the body and combines with phosphorus to form calcium phosphate in the bones and teeth. It is essential for the normal functioning of nerves and muscles and plays a role in blood coagulation (as factor IV) and in many enzymatic processes. [NIH] Calcium channel blocker: A drug used to relax the blood vessel and heart muscle, causing pressure inside blood vessels to drop. It also can regulate heart rhythm. [NIH] Calcium Channels: Voltage-dependent cell membrane glycoproteins selectively permeable to calcium ions. They are categorized as L-, T-, N-, P-, Q-, and R-types based on the activation and inactivation kinetics, ion specificity, and sensitivity to drugs and toxins. The L- and T-types are present throughout the cardiovascular and central nervous systems and the N-, P-, Q-, & R-types are located in neuronal tissue. [NIH] Calculi: An abnormal concretion occurring mostly in the urinary and biliary tracts, usually


composed of mineral salts. Also called stones. [NIH] Candidiasis: Infection with a fungus of the genus Candida. It is usually a superficial infection of the moist cutaneous areas of the body, and is generally caused by C. albicans; it most commonly involves the skin (dermatocandidiasis), oral mucous membranes (thrush, def. 1), respiratory tract (bronchocandidiasis), and vagina (vaginitis). Rarely there is a systemic infection or endocarditis. Called also moniliasis, candidosis, oidiomycosis, and formerly blastodendriosis. [EU] Candidosis: An infection caused by an opportunistic yeasts that tends to proliferate and become pathologic when the environment is favorable and the host resistance is weakened. [NIH]

Carbohydrate: An aldehyde or ketone derivative of a polyhydric alcohol, particularly of the pentahydric and hexahydric alcohols. They are so named because the hydrogen and oxygen are usually in the proportion to form water, (CH2O)n. The most important carbohydrates are the starches, sugars, celluloses, and gums. They are classified into mono-, di-, tri-, polyand heterosaccharides. [EU] Carbon Dioxide: A colorless, odorless gas that can be formed by the body and is necessary for the respiration cycle of plants and animals. [NIH] Carcinogenic: Producing carcinoma. [EU] Carcinoma: Cancer that begins in the skin or in tissues that line or cover internal organs. [NIH]

Cardiac: Having to do with the heart. [NIH] Cardiovascular: Having to do with the heart and blood vessels. [NIH] Cardiovascular System: The heart and the blood vessels by which blood is pumped and circulated through the body. [NIH] Carrier Proteins: Transport proteins that carry specific substances in the blood or across cell membranes. [NIH] Case report: A detailed report of the diagnosis, treatment, and follow-up of an individual patient. Case reports also contain some demographic information about the patient (for example, age, gender, ethnic origin). [NIH] Case series: A group or series of case reports involving patients who were given similar treatment. Reports of case series usually contain detailed information about the individual patients. This includes demographic information (for example, age, gender, ethnic origin) and information on diagnosis, treatment, response to treatment, and follow-up after treatment. [NIH] 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] Catecholamine: A group of chemical substances manufactured by the adrenal medulla and secreted during physiological stress. [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] Celiac Disease: A disease characterized by intestinal malabsorption and precipitated by gluten-containing foods. The intestinal mucosa shows loss of villous structure. [NIH]

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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 Death: The termination of the cell's ability to carry out vital functions such as metabolism, growth, reproduction, responsiveness, and adaptability. [NIH] Cell Differentiation: Progressive restriction of the developmental potential and increasing specialization of function which takes place during the development of the embryo and leads to the formation of specialized cells, tissues, and organs. [NIH] Cell Division: The fission of a cell. [NIH] Cell membrane: Cell membrane = plasma membrane. The structure enveloping a cell, enclosing the cytoplasm, and forming a selective permeability barrier; it consists of lipids, proteins, and some carbohydrates, the lipids thought to form a bilayer in which integral proteins are embedded to varying degrees. [EU] Cell proliferation: An increase in the number of cells as a result of cell growth and cell division. [NIH] Cell Size: The physical dimensions of a cell. It refers mainly to changes in dimensions correlated with physiological or pathological changes in cells. [NIH] Cell Survival: The span of viability of a cell characterized by the capacity to perform certain functions such as metabolism, growth, reproduction, some form of responsiveness, and adaptability. [NIH] Cell Transplantation: Transference of cells within an individual, between individuals of the same species, or between individuals of different species. [NIH] Cellulose: A polysaccharide with glucose units linked as in cellobiose. It is the chief constituent of plant fibers, cotton being the purest natural form of the substance. As a raw material, it forms the basis for many derivatives used in chromatography, ion exchange materials, explosives manufacturing, and pharmaceutical preparations. [NIH] Central Nervous System: The main information-processing organs of the nervous system, consisting of the brain, spinal cord, and meninges. [NIH] Central Nervous System Infections: Pathogenic infections of the brain, spinal cord, and meninges. DNA virus infections; RNA virus infections; bacterial infections; mycoplasma infections; Spirochaetales infections; fungal infections; protozoan infections; helminthiasis; and prion diseases may involve the central nervous system as a primary or secondary process. [NIH] Cerebellar: Pertaining to the cerebellum. [EU] Cerebellar Diseases: Diseases that affect the structure or function of the cerebellum. Cardinal manifestations of cerebellar dysfunction include dysmetria, gait ataxia, and muscle hypotonia. [NIH] Cerebral: Of or pertaining of the cerebrum or the brain. [EU] Cerebral Infarction: The formation of an area of necrosis in the cerebrum caused by an insufficiency of arterial or venous blood flow. Infarcts of the cerebrum are generally classified by hemisphere (i.e., left vs. right), lobe (e.g., frontal lobe infarction), arterial distribution (e.g., infarction, anterior cerebral artery), and etiology (e.g., embolic infarction).


[NIH]

Cerebral Palsy: Refers to a motor disability caused by a brain dysfunction. [NIH] Cerebrospinal: Pertaining to the brain and spinal cord. [EU] Cerebrospinal fluid: CSF. The fluid flowing around the brain and spinal cord. Cerebrospinal fluid is produced in the ventricles in the brain. [NIH] Cerebrovascular: Pertaining to the blood vessels of the cerebrum, or brain. [EU] Cerebrum: The largest part of the brain. It is divided into two hemispheres, or halves, called the cerebral hemispheres. The cerebrum controls muscle functions of the body and also controls speech, emotions, reading, writing, and learning. [NIH] Cervical: Relating to the neck, or to the neck of any organ or structure. Cervical lymph nodes are located in the neck; cervical cancer refers to cancer of the uterine cervix, which is the lower, narrow end (the "neck") of the uterus. [NIH] Cervical Plexus: A network of nerve fibers originating in the upper four cervical spinal cord segments. The cervical plexus distributes cutaneous nerves to parts of the neck, shoulders, and back of the head, and motor fibers to muscles of the cervical spinal column, infrahyoid muscles, and the diaphragm. [NIH] Cervix: The lower, narrow end of the uterus that forms a canal between the uterus and vagina. [NIH] Character: In current usage, approximately equivalent to personality. The sum of the relatively fixed personality traits and habitual modes of response of an individual. [NIH] Chelation: Combination with a metal in complexes in which the metal is part of a ring. [EU] Chelation Therapy: Therapy of heavy metal poisoning using agents which sequester the metal from organs or tissues and bind it firmly within the ring structure of a new compound which can be eliminated from the body. [NIH] Chemokines: Class of pro-inflammatory cytokines that have the ability to attract and activate leukocytes. They can be divided into at least three structural branches: C (chemokines, C), CC (chemokines, CC), and CXC (chemokines, CXC), according to variations in a shared cysteine motif. [NIH] Chemotactic Factors: Chemical substances that attract or repel cells or organisms. The concept denotes especially those factors released as a result of tissue injury, invasion, or immunologic activity, that attract leukocytes, macrophages, or other cells to the site of infection or insult. [NIH] Chemotherapy: Treatment with anticancer drugs. [NIH] Chest Pain: Pressure, burning, or numbness in the chest. [NIH] Cholesterol: The principal sterol of all higher animals, distributed in body tissues, especially the brain and spinal cord, and in animal fats and oils. [NIH] Choline: A basic constituent of lecithin that is found in many plants and animal organs. It is important as a precursor of acetylcholine, as a methyl donor in various metabolic processes, and in lipid metabolism. [NIH] Cholinergic: Resembling acetylcholine in pharmacological action; stimulated by or releasing acetylcholine or a related compound. [EU] Cholinergic Agents: Any drug used for its actions on cholinergic systems. Included here are agonists and antagonists, drugs that affect the life cycle of acetylcholine, and drugs that affect the survival of cholinergic neurons. The term cholinergic agents is sometimes still used in the narrower sense of muscarinic agonists, although most modern texts discourage that usage. [NIH]

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Cholinesterase Inhibitors: Drugs that inhibit cholinesterases. The neurotransmitter acetylcholine is rapidly hydrolyzed, and thereby inactivated, by cholinesterases. When cholinesterases are inhibited, the action of endogenously released acetylcholine at cholinergic synapses is potentiated. Cholinesterase inhibitors are widely used clinically for their potentiation of cholinergic inputs to the gastrointestinal tract and urinary bladder, the eye, and skeletal muscles; they are also used for their effects on the heart and the central nervous system. [NIH] Chorea: Involuntary, forcible, rapid, jerky movements that may be subtle or become confluent, markedly altering normal patterns of movement. Hypotonia and pendular reflexes are often associated. Conditions which feature recurrent or persistent episodes of chorea as a primary manifestation of disease are referred to as choreatic disorders. Chorea is also a frequent manifestation of basal ganglia diseases. [NIH] Choreatic Disorders: Acquired and hereditary conditions which feature chorea as a primary manifestation of the disease process. [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] Chromosome: Part of a cell that contains genetic information. Except for sperm and eggs, all human cells contain 46 chromosomes. [NIH] Chronic: A disease or condition that persists or progresses over a long period of time. [NIH] Chronic Disease: Disease or ailment of long duration. [NIH] Chymopapain: A cysteine endopeptidase isolated from papaya latex. Preferential cleavage at glutamic and aspartic acid residues. EC 3.4.22.6. [NIH] Ciliary: Inflammation or infection of the glands of the margins of the eyelids. [NIH] Ciliary Body: A ring of tissue extending from the scleral spur to the ora serrata of the retina. It consists of the uveal portion and the epithelial portion. The ciliary muscle is in the uveal portion and the ciliary processes are in the epithelial portion. [NIH] Ciliary Neurotrophic Factor: A neurotrophic factor that promotes the survival of various neuronal cell types and may play an important role in the injury response in the nervous system. [NIH] Circulatory system: The system that contains the heart and the blood vessels and moves blood throughout the body. This system helps tissues get enough oxygen and nutrients, and it helps them get rid of waste products. The lymph system, which connects with the blood system, is often considered part of the circulatory system. [NIH] CIS: Cancer Information Service. The CIS is the National Cancer Institute's link to the public, interpreting and explaining research findings in a clear and understandable manner, and providing personalized responses to specific questions about cancer. Access the CIS by calling 1-800-4-CANCER, or by using the Web site at http://cis.nci.nih.gov. [NIH] Clamp: A u-shaped steel rod used with a pin or wire for skeletal traction in the treatment of certain fractures. [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] 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] Coal: A natural fuel formed by partial decomposition of vegetable matter under certain environmental conditions. [NIH] Coca: Any of several South American shrubs of the Erythroxylon genus (and family) that yield cocaine; the leaves are chewed with alum for CNS stimulation. [NIH] Cocaine: An alkaloid ester extracted from the leaves of plants including coca. It is a local anesthetic and vasoconstrictor and is clinically used for that purpose, particularly in the eye, ear, nose, and throat. It also has powerful central nervous system effects similar to the amphetamines and is a drug of abuse. Cocaine, like amphetamines, acts by multiple mechanisms on brain catecholaminergic neurons; the mechanism of its reinforcing effects is thought to involve inhibition of dopamine uptake. [NIH] Cochlea: The part of the internal ear that is concerned with hearing. It forms the anterior part of the labyrinth, is conical, and is placed almost horizontally anterior to the vestibule. [NIH]

Cochlear: Of or pertaining to the cochlea. [EU] Cochlear Diseases: Diseases of the cochlea, the part of the inner ear that is concerned with hearing. [NIH] Cofactor: A substance, microorganism or environmental factor that activates or enhances the action of another entity such as a disease-causing agent. [NIH] Cognition: Intellectual or mental process whereby an organism becomes aware of or obtains knowledge. [NIH] Colitis: Inflammation of the colon. [NIH] Collagen: A polypeptide substance comprising about one third of the total protein in mammalian organisms. It is the main constituent of skin, connective tissue, and the organic substance of bones and teeth. Different forms of collagen are produced in the body but all consist of three alpha-polypeptide chains arranged in a triple helix. Collagen is differentiated from other fibrous proteins, such as elastin, by the content of proline, hydroxyproline, and hydroxylysine; by the absence of tryptophan; and particularly by the high content of polar groups which are responsible for its swelling properties. [NIH] 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] Communication Disorders: Disorders of verbal and nonverbal communication caused by receptive or expressive language disorders, cognitive dysfunction (e.g., mental retardation), psychiatric conditions, and hearing disorders. [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

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system) and complement regulatory proteins are known by semisystematic or trivial names. Fragments resulting from proteolytic cleavage of complement proteins are designated with lower-case letter suffixes, e.g., C3a. Inactivated fragments may be designated with the suffix 'i', e.g. C3bi. Activated components or complexes with biological activity are designated by a bar over the symbol e.g. C1 or C4b,2a. The classic pathway is activated by the binding of C1 to classic pathway activators, primarily antigen-antibody complexes containing IgM, IgG1, IgG3; C1q binds to a single IgM molecule or two adjacent IgG molecules. The alternative pathway can be activated by IgA immune complexes and also by nonimmunologic materials including bacterial endotoxins, microbial polysaccharides, and cell walls. Activation of the classic pathway triggers an enzymatic cascade involving C1, C4, C2 and C3; activation of the alternative pathway triggers a cascade involving C3 and factors B, D and P. Both result in the cleavage of C5 and the formation of the membrane attack complex. Complement activation also results in the formation of many biologically active complement fragments that act as anaphylatoxins, opsonins, or chemotactic factors. [EU] Complement Activation: The sequential activation of serum components C1 through C9, initiated by an erythrocyte-antibody complex or by microbial polysaccharides and properdin, and producing an inflammatory response. [NIH] Complementary and alternative medicine: CAM. Forms of treatment that are used in addition to (complementary) or instead of (alternative) standard treatments. These practices are not considered standard medical approaches. CAM includes dietary supplements, megadose vitamins, herbal preparations, special teas, massage therapy, magnet therapy, spiritual healing, and meditation. [NIH] Complementary medicine: Practices not generally recognized by the medical community as standard or conventional medical approaches and used to enhance or complement the standard treatments. Complementary medicine includes the taking of dietary supplements, megadose vitamins, and herbal preparations; the drinking of special teas; and practices such as massage therapy, magnet therapy, spiritual healing, and meditation. [NIH] Complete remission: The disappearance of all signs of cancer. Also called a complete response. [NIH] Complete response: The disappearance of all signs of cancer in response to treatment. This does not always mean the cancer has been cured. [NIH] Computational Biology: A field of biology concerned with the development of techniques for the collection and manipulation of biological data, and the use of such data to make biological discoveries or predictions. This field encompasses all computational methods and theories applicable to molecular biology and areas of computer-based techniques for solving biological problems including manipulation of models and datasets. [NIH] Conception: The onset of pregnancy, marked by implantation of the blastocyst; the formation of a viable zygote. [EU] Conduction: The transfer of sound waves, heat, nervous impulses, or electricity. [EU] Congenita: Displacement, subluxation, or malposition of the crystalline lens. [NIH] Congestion: Excessive or abnormal accumulation of blood in a part. [EU] Conjugated: Acting or operating as if joined; simultaneous. [EU] Conjunctiva: The mucous membrane that lines the inner surface of the eyelids and the anterior part of the sclera. [NIH] Connective Tissue: Tissue that supports and binds other tissues. It consists of connective tissue cells embedded in a large amount of extracellular matrix. [NIH] Connective Tissue: Tissue that supports and binds other tissues. It consists of connective


tissue cells embedded in a large amount of extracellular matrix. [NIH] Consciousness: Sense of awareness of self and of the environment. [NIH] Constitutional: 1. Affecting the whole constitution of the body; not local. 2. Pertaining to the constitution. [EU] Consumption: Pulmonary tuberculosis. [NIH] 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] Controlled study: An experiment or clinical trial that includes a comparison (control) group. [NIH]

Coordination: Muscular or motor regulation or the harmonious cooperation of muscles or groups of muscles, in a complex action or series of actions. [NIH] Cornea: The transparent part of the eye that covers the iris and the pupil and allows light to enter the inside. [NIH] 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] 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 Thrombosis: Presence of a thrombus in a coronary artery, often causing a myocardial infarction. [NIH] Cortex: The outer layer of an organ or other body structure, as distinguished from the internal substance. [EU] Cortical: Pertaining to or of the nature of a cortex or bark. [EU] Corticosteroid: Any of the steroids elaborated by the adrenal cortex (excluding the sex hormones of adrenal origin) in response to the release of corticotrophin (adrenocorticotropic hormone) by the pituitary gland, to any of the synthetic equivalents of these steroids, or to angiotensin II. They are divided, according to their predominant biological activity, into three major groups: glucocorticoids, chiefly influencing carbohydrate, fat, and protein metabolism; mineralocorticoids, affecting the regulation of electrolyte and water balance; and C19 androgens. Some corticosteroids exhibit both types of activity in varying degrees, and others exert only one type of effect. The corticosteroids are used clinically for hormonal replacement therapy, for suppression of ACTH secretion by the anterior pituitary, as antineoplastic, antiallergic, and anti-inflammatory agents, and to suppress the immune response. Called also adrenocortical hormone and corticoid. [EU] Cortisol: A steroid hormone secreted by the adrenal cortex as part of the body's response to stress. [NIH] Cortisone: A natural steroid hormone produced in the adrenal gland. It can also be made in the laboratory. Cortisone reduces swelling and can suppress immune responses. [NIH] Cowpox: A mild, eruptive skin disease of milk cows caused by cowpox virus, with lesions occurring principally on the udder and teats. Human infection may occur while milking an infected animal. [NIH] Cowpox Virus: A species of orthopoxvirus that is the etiologic agent of cowpox. It is closely related to but antigenically different from vaccina virus. [NIH] Cranial: Pertaining to the cranium, or to the anterior (in animals) or superior (in humans) end of the body. [EU] Cranial Nerves: Twelve pairs of nerves that carry general afferent, visceral afferent, special

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afferent, somatic efferent, and autonomic efferent fibers. [NIH] Craniocerebral Trauma: Traumatic injuries involving the cranium and intracranial structures (i.e., brain; cranial nerves; meninges; and other structures). Injuries may be classified by whether or not the skull is penetrated (i.e., penetrating vs. nonpenetrating) or whether there is an associated hemorrhage. [NIH] Creatine: An amino acid that occurs in vertebrate tissues and in urine. In muscle tissue, creatine generally occurs as phosphocreatine. Creatine is excreted as creatinine in the urine. [NIH]

Creatinine: A compound that is excreted from the body in urine. Creatinine levels are measured to monitor kidney function. [NIH] Cricoid Cartilage: The small thick cartilage that forms the lower and posterior parts of the laryngeal wall. [NIH] Critical Care: Health care provided to a critically ill patient during a medical emergency or crisis. [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] 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] 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] Cyclophosphamide: Precursor of an alkylating nitrogen mustard antineoplastic and immunosuppressive agent that must be activated in the liver to form the active aldophosphamide. It is used in the treatment of lymphomas, leukemias, etc. Its side effect, alopecia, has been made use of in defleecing sheep. Cyclophosphamide may also cause sterility, birth defects, mutations, and cancer. [NIH] Cyclosporine: A drug used to help reduce the risk of rejection of organ and bone marrow transplants by the body. It is also used in clinical trials to make cancer cells more sensitive to anticancer drugs. [NIH] Cyst: A sac or capsule filled with fluid. [NIH] Cysteine: A thiol-containing non-essential amino acid that is oxidized to form cystine. [NIH] Cytokine: Small but highly potent protein that modulates the activity of many cell types, including T and B cells. [NIH] Cytoplasm: The protoplasm of a cell exclusive of that of the nucleus; it consists of a continuous aqueous solution (cytosol) and the organelles and inclusions suspended in it (phaneroplasm), and is the site of most of the chemical activities of the cell. [EU] 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]

Cytotoxic: Cell-killing. [NIH] Databases, Bibliographic: Extensive collections, reputedly complete, of references and citations to books, articles, publications, etc., generally on a single subject or specialized


subject area. Databases can operate through automated files, libraries, or computer disks. The concept should be differentiated from factual databases which is used for collections of data and facts apart from bibliographic references to them. [NIH] Deanol: An antidepressive agent that has also been used in the treatment of movement disorders. The mechanism of action is not well understood. [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] 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] Delirium: (DSM III-R) an acute, reversible organic mental disorder characterized by reduced ability to maintain attention to external stimuli and disorganized thinking as manifested by rambling, irrelevant, or incoherent speech; there are also a reduced level of consciousness, sensory misperceptions, disturbance of the sleep-wakefulness cycle and level of psychomotor activity, disorientation to time, place, or person, and memory impairment. Delirium may be caused by a large number of conditions resulting in derangement of cerebral metabolism, including systemic infection, poisoning, drug intoxication or withdrawal, seizures or head trauma, and metabolic disturbances such as hypoxia, hypoglycaemia, fluid, electrolyte, or acid-base imbalances, or hepatic or renal failure. Called also acute confusional state and acute brain syndrome. [EU] Dementia: An acquired organic mental disorder with loss of intellectual abilities of sufficient severity to interfere with social or occupational functioning. The dysfunction is multifaceted and involves memory, behavior, personality, judgment, attention, spatial relations, language, abstract thought, and other executive functions. The intellectual decline is usually progressive, and initially spares the level of consciousness. [NIH] Dendrites: Extensions of the nerve cell body. They are short and branched and receive stimuli from other neurons. [NIH] 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 Care: The total of dental diagnostic, preventive, and restorative services provided to meet the needs of a patient (from Illustrated Dictionary of Dentistry, 1982). [NIH] Depigmentation: Removal or loss of pigment, especially melanin. [EU] Desensitization: The prevention or reduction of immediate hypersensitivity reactions by administration of graded doses of allergen; called also hyposensitization and immunotherapy. [EU] Deuterium: Deuterium. The stable isotope of hydrogen. It has one neutron and one proton in the nucleus. [NIH] Dexamethasone: (11 beta,16 alpha)-9-Fluoro-11,17,21-trihydroxy-16-methylpregna-1,4diene-3,20-dione. An anti-inflammatory glucocorticoid used either in the free alcohol or esterified form in treatment of conditions that respond generally to cortisone. [NIH] Dexterity: Ability to move the hands easily and skillfully. [NIH] Diabetes Mellitus: A heterogeneous group of disorders that share glucose intolerance in common. [NIH] Diagnostic Imaging: Any visual display of structural or functional patterns of organs or

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tissues for diagnostic evaluation. It includes measuring physiologic and metabolic responses to physical and chemical stimuli, as well as ultramicroscopy. [NIH] Diagnostic procedure: A method used to identify a disease. [NIH] Diaphragm: The musculofibrous partition that separates the thoracic cavity from the abdominal cavity. Contraction of the diaphragm increases the volume of the thoracic cavity aiding inspiration. [NIH] Diarrhea: Passage of excessively liquid or excessively frequent stools. [NIH] Digestion: The process of breakdown of food for metabolism and use by the body. [NIH] Digestive system: The organs that take in food and turn it into products that the body can use to stay healthy. Waste products the body cannot use leave the body through bowel movements. The digestive system includes the salivary glands, mouth, esophagus, stomach, liver, pancreas, gallbladder, small and large intestines, and rectum. [NIH] Digestive tract: The organs through which food passes when food is eaten. These organs are the mouth, esophagus, stomach, small and large intestines, and rectum. [NIH] Dilatation: The act of dilating. [NIH] Dilation: A process by which the pupil is temporarily enlarged with special eye drops (mydriatic); allows the eye care specialist to better view the inside of the eye. [NIH] Diploid: Having two sets of chromosomes. [NIH] Diplopia: A visual symptom in which a single object is perceived by the visual cortex as two objects rather than one. Disorders associated with this condition include refractive errors; strabismus; oculomotor nerve diseases; trochlear nerve diseases; abducens nerve diseases; and diseases of the brain stem and occipital lobe. [NIH] Direct: 1. Straight; in a straight line. 2. Performed immediately and without the intervention of subsidiary means. [EU] Discrimination: The act of qualitative and/or quantitative differentiation between two or more stimuli. [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] Disease Susceptibility: A constitution or condition of the body which makes the tissues react in special ways to certain extrinsic stimuli and thus tends to make the individual more than usually susceptible to certain diseases. [NIH] Disinfectant: An agent that disinfects; applied particularly to agents used on inanimate objects. [EU] Dislocation: The displacement of any part, more especially of a bone. Called also luxation. [EU]

Disorientation: The loss of proper bearings, or a state of mental confusion as to time, place, or identity. [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] 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] Dizziness: An imprecise term which may refer to a sense of spatial disorientation, motion of the environment, or lightheadedness. [NIH] Donepezil: A drug used in the treatment of Alzheimer's disease. It belongs to the family of drugs called cholinesterase inhibitors. It is being studied as a treatment for side effects caused by radiation therapy to the brain. [NIH] Dopamine: An endogenous catecholamine and prominent neurotransmitter in several systems of the brain. In the synthesis of catecholamines from tyrosine, it is the immediate precursor to norepinephrine and epinephrine. Dopamine is a major transmitter in the extrapyramidal system of the brain, and important in regulating movement. A family of dopaminergic receptor subtypes mediate its action. Dopamine is used pharmacologically for its direct (beta adrenergic agonist) and indirect (adrenergic releasing) sympathomimetic effects including its actions as an inotropic agent and as a renal vasodilator. [NIH] Dorsal: 1. Pertaining to the back or to any dorsum. 2. Denoting a position more toward the back surface than some other object of reference; same as posterior in human anatomy; superior in the anatomy of quadrupeds. [EU] Dorsum: A plate of bone which forms the posterior boundary of the sella turcica. [NIH] 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 Approval: Process that is gone through in order for a drug to receive approval by a government regulatory agency. This includes any required pre-clinical or clinical testing, review, submission, and evaluation of the applications and test results, and post-marketing surveillance of the drug. [NIH] Drug Design: The molecular designing of drugs for specific purposes (such as DNAbinding, enzyme inhibition, anti-cancer efficacy, etc.) based on knowledge of molecular properties such as activity of functional groups, molecular geometry, and electronic structure, and also on information cataloged on analogous molecules. Drug design is generally computer-assisted molecular modeling and does not include pharmacokinetics, dosage analysis, or drug administration analysis. [NIH] Drug Interactions: The action of a drug that may affect the activity, metabolism, or toxicity of another drug. [NIH] Drug Tolerance: Progressive diminution of the susceptibility of a human or animal to the effects of a drug, resulting from its continued administration. It should be differentiated from drug resistance wherein an organism, disease, or tissue fails to respond to the intended effectiveness of a chemical or drug. It should also be differentiated from maximum tolerated dose and no-observed-adverse-effect level. [NIH] Duodenum: The first part of the small intestine. [NIH] Dyes: Chemical substances that are used to stain and color other materials. The coloring may or may not be permanent. Dyes can also be used as therapeutic agents and test reagents in medicine and scientific research. [NIH] Dysarthria: Imperfect articulation of speech due to disturbances of muscular control which result from damage to the central or peripheral nervous system. [EU] Dyskinesia: Impairment of the power of voluntary movement, resulting in fragmentary or

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incomplete movements. [EU] Dyslexia: Partial alexia in which letters but not words may be read, or in which words may be read but not understood. [NIH] Dysphagia: Difficulty in swallowing. [EU] Dysphonia: Difficulty or pain in speaking; impairment of the voice. [NIH] Dystonia: Disordered tonicity of muscle. [EU] Dystrophin: A muscle protein localized in surface membranes which is the product of the Duchenne/Becker muscular dystrophy gene. Individuals with Duchenne muscular dystrophy usually lack dystrophin completely while those with Becker muscular dystrophy have dystrophin of an altered size. It shares features with other cytoskeletal proteins such as spectrin and alpha-actinin but the precise function of dystrophin is not clear. One possible role might be to preserve the integrity and alignment of the plasma membrane to the myofibrils during muscle contraction and relaxation. MW 400 kDa. [NIH] Dystrophy: Any disorder arising from defective or faulty nutrition, especially the muscular dystrophies. [EU] Eating Disorders: A group of disorders characterized by physiological and psychological disturbances in appetite or food intake. [NIH] Effector: It is often an enzyme that converts an inactive precursor molecule into an active second messenger. [NIH] Effector cell: A cell that performs a specific function in response to a stimulus; usually used to describe cells in the immune system. [NIH] Efficacy: The extent to which a specific intervention, procedure, regimen, or service produces a beneficial result under ideal conditions. Ideally, the determination of efficacy is based on the results of a randomized control trial. [NIH] Elective: Subject to the choice or decision of the patient or physician; applied to procedures that are advantageous to the patient but not urgent. [EU] Electrolyte: A substance that dissociates into ions when fused or in solution, and thus becomes capable of conducting electricity; an ionic solute. [EU] Electromyography: Recording of the changes in electric potential of muscle by means of surface or needle electrodes. [NIH] Electrons: Stable elementary particles having the smallest known negative charge, present in all elements; also called negatrons. Positively charged electrons are called positrons. The numbers, energies and arrangement of electrons around atomic nuclei determine the chemical identities of elements. Beams of electrons are called cathode rays or beta rays, the latter being a high-energy biproduct of nuclear decay. [NIH] 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] Elementary Particles: Individual components of atoms, usually subatomic; subnuclear particles are usually detected only when the atomic nucleus decays and then only transiently, as most of them are unstable, often yielding pure energy without substance, i.e., radiation. [NIH] Embryo: The prenatal stage of mammalian development characterized by rapid morphological changes and the differentiation of basic structures. [NIH] Embryo Transfer: Removal of a mammalian embryo from one environment and replacement in the same or a new environment. The embryo is usually in the pre-nidation


phase, i.e., a blastocyst. The process includes embryo or blastocyst transplantation or transfer after in vitro fertilization and transfer of the inner cell mass of the blastocyst. It is not used for transfer of differentiated embryonic tissue, e.g., germ layer cells. [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] Encephalitis: Inflammation of the brain due to infection, autoimmune processes, toxins, and other conditions. Viral infections (see encephalitis, viral) are a relatively frequent cause of this condition. [NIH] Encephalitis, Viral: Inflammation of brain parenchymal tissue as a result of viral infection. Encephalitis may occur as primary or secondary manifestation of Togaviridae infections; Herpesviridae infections; Adenoviridae infections; Flaviviridae infections; Bunyaviridae infections; Picornaviridae infections; Paramyxoviridae infections; Orthomyxoviridae infections; Retroviridae infections; and Arenaviridae infections. [NIH] Encephalocele: Cerebral tissue herniation through a congenital or acquired defect in the skull. The majority of congenital encephaloceles occur in the occipital or frontal regions. Clinical features include a protuberant mass that may be pulsatile. The quantity and location of protruding neural tissue determines the type and degree of neurologic deficit. Visual defects, psychomotor developmental delay, and persistent motor deficits frequently occur. [NIH]

Encephalomyelitis: A general term indicating inflammation of the brain and spinal cord, often used to indicate an infectious process, but also applicable to a variety of autoimmune and toxic-metabolic conditions. There is significant overlap regarding the usage of this term and encephalitis in the literature. [NIH] Encephalopathy: A disorder of the brain that can be caused by disease, injury, drugs, or chemicals. [NIH] Endocarditis: Exudative and proliferative inflammatory alterations of the endocardium, characterized by the presence of vegetations on the surface of the endocardium or in the endocardium itself, and most commonly involving a heart valve, but sometimes affecting the inner lining of the cardiac chambers or the endocardium elsewhere. It may occur as a primary disorder or as a complication of or in association with another disease. [EU] Endocrine System: The system of glands that release their secretions (hormones) directly into the circulatory system. In addition to the endocrine glands, included are the chromaffin system and the neurosecretory systems. [NIH] 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] Endoscope: A thin, lighted tube used to look at tissues inside the body. [NIH] Endoscopy: Endoscopic examination, therapy or surgery performed on interior parts of the

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body. [NIH] Endothelial cell: The main type of cell found in the inside lining of blood vessels, lymph vessels, and the heart. [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] Enteropeptidase: A specialized proteolytic enzyme secreted by intestinal cells. It converts trypsinogen into its active form trypsin by removing the N-terminal peptide. EC 3.4.21.9. [NIH]

Environmental Exposure: The exposure to potentially harmful chemical, physical, or biological agents in the environment or to environmental factors that may include ionizing radiation, pathogenic organisms, or toxic chemicals. [NIH] Environmental Health: The science of controlling or modifying those conditions, influences, or forces surrounding man which relate to promoting, establishing, and maintaining health. [NIH]

Enzymatic: Phase where enzyme cuts the precursor protein. [NIH] Enzyme: A protein that speeds up chemical reactions in the body. [NIH] Eosinophils: Granular leukocytes with a nucleus that usually has two lobes connected by a slender thread of chromatin, and cytoplasm containing coarse, round granules that are uniform in size and stainable by eosin. [NIH] Epidemiological: Relating to, or involving epidemiology. [EU] 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] Epidural: The space between the wall of the spinal canal and the covering of the spinal cord. An epidural injection is given into this space. [NIH] 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] 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]

Epitope Mapping: Methods used for studying the interactions of antibodies with specific regions of protein antigens. Important applications of epitope mapping are found within the area of immunochemistry. [NIH] Erythema: Redness of the skin produced by congestion of the capillaries. This condition may result from a variety of causes. [NIH] Erythrocytes: Red blood cells. Mature erythrocytes are non-nucleated, biconcave disks


containing hemoglobin whose function is to transport oxygen. [NIH] Esophageal: Having to do with the esophagus, the muscular tube through which food passes from the throat to the stomach. [NIH] Esophageal Manometry: A test to measure muscle tone inthe esophagus. [NIH] Esophageal Motility Disorders: Disorders affecting the motor function of the upper or lower esophageal sphincters, the esophageal body, or a combination of these parts. The failure of the sphincters to maintain a tonic pressure may result in the impeding of the passage of food, regurgitation of food, or reflux of gastric acid into the esophagus. [NIH] Esophageal Spasms: Muscle cramps in the esophagus that cause pain in the chest. [NIH] Esophagram: A series of x-rays of the esophagus. The x-ray pictures are taken after the person drinks a solution that contains barium. The barium coats and outlines the esophagus on the x-ray. Also called a barium swallow. [NIH] Esophagus: The muscular tube through which food passes from the throat to the stomach. [NIH]

Esotropia: A form of ocular misalignment characterized by an excessive convergence of the visual axes, resulting in a "cross-eye" appearance. An example of this condition occurs when paralysis of the lateral rectus muscle causes an abnormal inward deviation of one eye on attempted gaze. [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] Eukaryotic Cells: Cells of the higher organisms, containing a true nucleus bounded by a nuclear membrane. [NIH] Evoke: The electric response recorded from the cerebral cortex after stimulation of a peripheral sense organ. [NIH] Evoked Potentials: The electric response evoked in the central nervous system by stimulation of sensory receptors or some point on the sensory pathway leading from the receptor to the cortex. The evoked stimulus can be auditory, somatosensory, or visual, although other modalities have been reported. Event-related potentials is sometimes used synonymously with evoked potentials but is often associated with the execution of a motor, cognitive, or psychophysiological task, as well as with the response to a stimulus. [NIH] Excitation: An act of irritation or stimulation or of responding to a stimulus; the addition of energy, as the excitation of a molecule by absorption of photons. [EU] Excitatory: When cortical neurons are excited, their output increases and each new input they receive while they are still excited raises their output markedly. [NIH] Exogenous: Developed or originating outside the organism, as exogenous disease. [EU] Exon: The part of the DNA that encodes the information for the actual amino acid sequence of the protein. In many eucaryotic genes, the coding sequences consist of a series of exons alternating with intron sequences. [NIH] Exophthalmos: Abnormal protrusion of both eyes; may be caused by endocrine gland malfunction, malignancy, injury, or paralysis of the extrinsic muscles of the eye. [NIH] Exotoxin: Toxic substance excreted by living bacterial cells. [NIH] Exotropia: A form of ocular misalignment where the visual axes diverge inappropriately. For example, medial rectus muscle weakness may produce this condition as the affected eye will deviate laterally upon attempted forward gaze. An exotropia occurs due to the

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relatively unopposed force exerted on the eye by the lateral rectus muscle, which pulls the eye in an outward direction. [NIH] Expiratory: The volume of air which leaves the breathing organs in each expiration. [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] Extraocular: External to or outside of the eye. [NIH] Extrapyramidal: Outside of the pyramidal tracts. [EU] Extremity: A limb; an arm or leg (membrum); sometimes applied specifically to a hand or foot. [EU] Eye Movements: Voluntary or reflex-controlled movements of the eye. [NIH] Facial: Of or pertaining to the face. [EU] Facial Pain: Pain in the facial region including orofacial pain and craniofacial pain. Associated conditions include local inflammatory and neoplastic disorders and neuralgic syndromes involving the trigeminal, facial, and glossopharyngeal nerves. Conditions which feature recurrent or persistent facial pain as the primary manifestation of disease are referred to as facial pain syndromes. [NIH] Facial Paralysis: Severe or complete loss of facial muscle motor function. This condition may result from central or peripheral lesions. Damage to CNS motor pathways from the cerebral cortex to the facial nuclei in the pons leads to facial weakness that generally spares the forehead muscles. Facial nerve diseases generally results in generalized hemifacial weakness. Neuromuscular junction diseases and muscular diseases may also cause facial paralysis or paresis. [NIH] Family Planning: Programs or services designed to assist the family in controlling reproduction by either improving or diminishing fertility. [NIH] Farnesyl: Enzyme which adds 15 carbon atoms to the Ras precursor protein. [NIH] Fasciculation: A small local contraction of muscles, visible through the skin, representing a spontaneous discharge of a number of fibres innervated by a single motor nerve filament. [EU]

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] Fertilization in Vitro: Fertilization of an egg outside the body when the egg is normally fertilized in the body. [NIH] Fetal Development: Morphologic and physiologic growth and development of the mammalian embryo or fetus. [NIH] Fetus: The developing offspring from 7 to 8 weeks after conception until birth. [NIH] Fibrosis: Any pathological condition where fibrous connective tissue invades any organ, usually as a consequence of inflammation or other injury. [NIH] Fixation: 1. The act or operation of holding, suturing, or fastening in a fixed position. 2. The condition of being held in a fixed position. 3. In psychiatry, a term with two related but distinct meanings : (1) arrest of development at a particular stage, which like regression (return to an earlier stage), if temporary is a normal reaction to setbacks and difficulties but if protracted or frequent is a cause of developmental failures and emotional problems, and (2) a close and suffocating attachment to another person, especially a childhood figure, such as one's mother or father. Both meanings are derived from psychoanalytic theory and refer to 'fixation' of libidinal energy either in a specific erogenous zone, hence fixation at the oral, anal, or phallic stage, or in a specific object, hence mother or father fixation. 4. The use of a fixative (q.v.) to preserve histological or cytological specimens. 5. In chemistry, the process whereby a substance is removed from the gaseous or solution phase and localized, as in carbon dioxide fixation or nitrogen fixation. 6. In ophthalmology, direction of the gaze so that the visual image of the object falls on the fovea centralis. 7. In film processing, the chemical removal of all undeveloped salts of the film emulsion, leaving only the developed silver to form a permanent image. [EU] Flow Cytometry: Technique using an instrument system for making, processing, and displaying one or more measurements on individual cells obtained from a cell suspension. Cells are usually stained with one or more fluorescent dyes specific to cell components of interest, e.g., DNA, and fluorescence of each cell is measured as it rapidly transverses the excitation beam (laser or mercury arc lamp). Fluorescence provides a quantitative measure of various biochemical and biophysical properties of the cell, as well as a basis for cell sorting. Other measurable optical parameters include light absorption and light scattering, the latter being applicable to the measurement of cell size, shape, density, granularity, and stain uptake. [NIH] Fluorescence: The property of emitting radiation while being irradiated. The radiation emitted is usually of longer wavelength than that incident or absorbed, e.g., a substance can be irradiated with invisible radiation and emit visible light. X-ray fluorescence is used in diagnosis. [NIH] Fluorescent Dyes: Dyes that emit light when exposed to light. The wave length of the emitted light is usually longer than that of the incident light. Fluorochromes are substances that cause fluorescence in other substances, i.e., dyes used to mark or label other compounds with fluorescent tags. They are used as markers in biochemistry and immunology. [NIH] Fold: A plication or doubling of various parts of the body. [NIH] Frontal Lobe: The anterior part of the cerebral hemisphere. [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

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asexually, and have life cycles that range from simple to complex. Filamentous fungi refer to those that grow as multicelluar colonies (mushrooms and molds). [NIH] Fungus: A general term used to denote a group of eukaryotic protists, including mushrooms, yeasts, rusts, moulds, smuts, etc., which are characterized by the absence of chlorophyll and by the presence of a rigid cell wall composed of chitin, mannans, and sometimes cellulose. They are usually of simple morphological form or show some reversible cellular specialization, such as the formation of pseudoparenchymatous tissue in the fruiting body of a mushroom. The dimorphic fungi grow, according to environmental conditions, as moulds or yeasts. [EU] Galactosides: Glycosides formed by the reaction of the hydroxyl group on the anomeric carbon atom of galactose with an alcohol to form an acetal. They include both alpha- and beta-galactosides. [NIH] Gallbladder: The pear-shaped organ that sits below the liver. Bile is concentrated and stored in the gallbladder. [NIH] 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] Ganglionic Blockers: Agents having as their major action the interruption of neural transmission at nicotinic receptors on postganglionic autonomic neurons. Because their actions are so broad, including blocking of sympathetic and parasympathetic systems, their therapeutic use has been largely supplanted by more specific drugs. They may still be used in the control of blood pressure in patients with acute dissecting aortic aneurysm and for the induction of hypotension in surgery. [NIH] Gap Junctions: Connections between cells which allow passage of small molecules and electric current. Gap junctions were first described anatomically as regions of close apposition between cells with a narrow (1-2 nm) gap between cell membranes. The variety in the properties of gap junctions is reflected in the number of connexins, the family of proteins which form the junctions. [NIH] Gas: Air that comes from normal breakdown of food. The gases are passed out of the body through the rectum (flatus) or the mouth (burp). [NIH] Gas exchange: Primary function of the lungs; transfer of oxygen from inhaled air into the blood and of carbon dioxide from the blood into the lungs. [NIH] Gasoline: Volative flammable fuel (liquid hydrocarbons) derived from crude petroleum by processes such as distillation reforming, polymerization, etc. [NIH] Gastric: Having to do with the stomach. [NIH] Gastric Acid: Hydrochloric acid present in gastric juice. [NIH] Gastric Juices: Liquids produced in the stomach to help break down food and kill bacteria. [NIH]

Gastrin: A hormone released after eating. Gastrin causes the stomach to produce more acid. [NIH]

Gastroesophageal Reflux: Reflux of gastric juice and/or duodenal contents (bile acids, pancreatic juice) into the distal esophagus, commonly due to incompetence of the lower esophageal sphincter. Gastric regurgitation is an extension of this process with entry of fluid


into the pharynx or mouth. [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] Gene: The functional and physical unit of heredity passed from parent to offspring. Genes are pieces of DNA, and most genes contain the information for making a specific protein. [NIH]

Gene Expression: The phenotypic manifestation of a gene or genes by the processes of gene action. [NIH] Gene Rearrangement: The ordered rearrangement of gene regions by DNA recombination such as that which occurs normally during development. [NIH] Gene Targeting: The integration of exogenous DNA into the genome of an organism at sites where its expression can be suitably controlled. This integration occurs as a result of homologous recombination. [NIH] Genetic Engineering: Directed modification of the gene complement of a living organism by such techniques as altering the DNA, substituting genetic material by means of a virus, transplanting whole nuclei, transplanting cell hybrids, etc. [NIH] Genetics: The biological science that deals with the phenomena and mechanisms of heredity. [NIH] Genital: Pertaining to the genitalia. [EU] Genotype: The genetic constitution of the individual; the characterization of the genes. [NIH] Germ Cells: The reproductive cells in multicellular organisms. [NIH] Germinal Center: The activated center of a lymphoid follicle in secondary lymphoid tissue where B-lymphocytes are stimulated by antigens and helper T cells (T-lymphocytes, helperinducer) are stimulated to generate memory cells. [NIH] Gestation: The period of development of the young in viviparous animals, from the time of fertilization of the ovum until birth. [EU] 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] Gliosis: The production of a dense fibrous network of neuroglia; includes astrocytosis, which is a proliferation of astrocytes in the area of a degenerative lesion. [NIH] Glossopharyngeal Nerve: The 9th cranial nerve. The glossopharyngeal nerve is a mixed motor and sensory nerve; it conveys somatic and autonomic efferents as well as general, special, and visceral afferents. Among the connections are motor fibers to the stylopharyngeus muscle, parasympathetic fibers to the parotid glands, general and taste afferents from the posterior third of the tongue, the nasopharynx, and the palate, and afferents from baroreceptors and chemoreceptors of the carotid sinus. [NIH] Glucocorticoid: A compound that belongs to the family of compounds called corticosteroids (steroids). Glucocorticoids affect metabolism and have anti-inflammatory and immunosuppressive effects. They may be naturally produced (hormones) or synthetic (drugs). [NIH] Glucose: D-Glucose. A primary source of energy for living organisms. It is naturally occurring and is found in fruits and other parts of plants in its free state. It is used

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therapeutically in fluid and nutrient replacement. [NIH] Glucose Intolerance: A pathological state in which the fasting plasma glucose level is less than 140 mg per deciliter and the 30-, 60-, or 90-minute plasma glucose concentration following a glucose tolerance test exceeds 200 mg per deciliter. This condition is seen frequently in diabetes mellitus but also occurs with other diseases. [NIH] Gluten: The protein of wheat and other grains which gives to the dough its tough elastic character. [EU] Glycerol: A trihydroxy sugar alcohol that is an intermediate in carbohydrate and lipid metabolism. It is used as a solvent, emollient, pharmaceutical agent, and sweetening agent. [NIH]

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] Glycoprotein: A protein that has sugar molecules attached to it. [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] Glycosylation: The chemical or biochemical addition of carbohydrate or glycosyl groups to other chemicals, especially peptides or proteins. Glycosyl transferases are used in this biochemical reaction. [NIH] Goiter: Enlargement of the thyroid gland. [NIH] Gonadal: Pertaining to a gonad. [EU] Gonads: The gamete-producing glands, ovary or testis. [NIH] 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 Rejection: An immune response with both cellular and humoral components, directed against an allogeneic transplant, whose tissue antigens are not compatible with those of the recipient. [NIH] Graft-versus-host disease: GVHD. A reaction of donated bone marrow or peripheral stem cells against a person's tissue. [NIH] Gram-negative: Losing the stain or decolorized by alcohol in Gram's method of staining, a primary characteristic of bacteria having a cell wall composed of a thin layer of peptidoglycan covered by an outer membrane of lipoprotein and lipopolysaccharide. [EU] Gravis: Eruption of watery blisters on the skin among those handling animals and animal products. [NIH]


Growth: The progressive development of a living being or part of an organism from its earliest stage to maturity. [NIH] Growth factors: Substances made by the body that function to regulate cell division and cell survival. Some growth factors are also produced in the laboratory and used in biological therapy. [NIH] Hair Cells: Mechanoreceptors located in the organ of Corti that are sensitive to auditory stimuli and in the vestibular apparatus that are sensitive to movement of the head. In each case the accessory sensory structures are arranged so that appropriate stimuli cause movement of the hair-like projections (stereocilia and kinocilia) which relay the information centrally in the nervous system. [NIH] Hair follicles: Shafts or openings on the surface of the skin through which hair grows. [NIH] Haploid: An organism with one basic chromosome set, symbolized by n; the normal condition of gametes in diploids. [NIH] Haptens: Small antigenic determinants capable of eliciting an immune response only when coupled to a carrier. Haptens bind to antibodies but by themselves cannot elicit an antibody response. [NIH] Headache: Pain in the cranial region that may occur as an isolated and benign symptom or as a manifestation of a wide variety of conditions including subarachnoid hemorrhage; craniocerebral trauma; central nervous system infections; intracranial hypertension; and other disorders. In general, recurrent headaches that are not associated with a primary disease process are referred to as headache disorders (e.g., migraine). [NIH] Headache Disorders: Common conditions characterized by persistent or recurrent headaches. Headache syndrome classification systems may be based on etiology (e.g., vascular headache, post-traumatic headaches, etc.), temporal pattern (e.g., cluster headache, paroxysmal hemicrania, etc.), and precipitating factors (e.g., cough headache). [NIH] Hearing Disorders: Conditions that impair the transmission or perception of auditory impulses and information from the level of the ear to the temporal cortices, including the sensorineural pathways. [NIH] Heart failure: Loss of pumping ability by the heart, often accompanied by fatigue, breathlessness, and excess fluid accumulation in body tissues. [NIH] Heartbeat: One complete contraction of the heart. [NIH] Hemoglobin: One of the fractions of glycosylated hemoglobin A1c. Glycosylated hemoglobin is formed when linkages of glucose and related monosaccharides bind to hemoglobin A and its concentration represents the average blood glucose level over the previous several weeks. HbA1c levels are used as a measure of long-term control of plasma glucose (normal, 4 to 6 percent). In controlled diabetes mellitus, the concentration of glycosylated hemoglobin A is within the normal range, but in uncontrolled cases the level may be 3 to 4 times the normal conentration. Generally, complications are substantially lower among patients with Hb levels of 7 percent or less than in patients with HbA1c levels of 9 percent or more. [NIH] Hemolytic: A disease that affects the blood and blood vessels. It destroys red blood cells, cells that cause the blood to clot, and the lining of blood vessels. HUS is often caused by the Escherichia coli bacterium in contaminated food. People with HUS may develop acute renal failure. [NIH] Hemorrhage: Bleeding or escape of blood from a vessel. [NIH] Hepatic: Refers to the liver. [NIH] Hepatitis: Inflammation of the liver and liver disease involving degenerative or necrotic

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alterations of hepatocytes. [NIH] Hepatocytes: The main structural component of the liver. They are specialized epithelial cells that are organized into interconnected plates called lobules. [NIH] Heredity: 1. The genetic transmission of a particular quality or trait from parent to offspring. 2. The genetic constitution of an individual. [EU] Heterodimer: Zippered pair of nonidentical proteins. [NIH] Heterogeneity: The property of one or more samples or populations which implies that they are not identical in respect of some or all of their parameters, e. g. heterogeneity of variance. [NIH]

Heterotropia: One in which the angle of squint remains relatively unaltered on conjugate movement of the eyes. [NIH] Histiocytosis: General term for the abnormal appearance of histiocytes in the blood. Based on the pathological features of the cells involved rather than on clinical findings, the histiocytic diseases are subdivided into three groups: Langerhans cell histiocytosis, nonLangerhans cell histiocytosis, and malignant histiocytic disorders. [NIH] Hoarseness: An unnaturally deep or rough quality of voice. [NIH] Homeostasis: The processes whereby the internal environment of an organism tends to remain balanced and stable. [NIH] Homologous: Corresponding in structure, position, origin, etc., as (a) the feathers of a bird and the scales of a fish, (b) antigen and its specific antibody, (c) allelic chromosomes. [EU] Hormonal: Pertaining to or of the nature of a hormone. [EU] Hormone: A substance in the body that regulates certain organs. Hormones such as gastrin help in breaking down food. Some hormones come from cells in the stomach and small intestine. [NIH] 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] Hybrid: Cross fertilization between two varieties or, more usually, two species of vines, see also crossing. [NIH] Hydrocephalus: Excessive accumulation of cerebrospinal fluid within the cranium which may be associated with dilation of cerebral ventricles, intracranial hypertension; headache; lethargy; urinary incontinence; and ataxia (and in infants macrocephaly). This condition may be caused by obstruction of cerebrospinal fluid pathways due to neurologic abnormalities, intracranial hemorrhages; central nervous system infections; brain neoplasms; craniocerebral trauma; and other conditions. Impaired resorption of cerebrospinal fluid from the arachnoid villi results in a communicating form of hydrocephalus. Hydrocephalus ex-vacuo refers to ventricular dilation that occurs as a result of brain substance loss from cerebral infarction and other conditions. [NIH] Hydrogen: The first chemical element in the periodic table. It has the atomic symbol H, atomic number 1, and atomic weight 1. It exists, under normal conditions, as a colorless, odorless, tasteless, diatomic gas. Hydrogen ions are protons. Besides the common H1 isotope, hydrogen exists as the stable isotope deuterium and the unstable, radioactive isotope tritium. [NIH]


Hydrolysis: The process of cleaving a chemical compound by the addition of a molecule of water. [NIH] Hyperplasia: An increase in the number of cells in a tissue or organ, not due to tumor formation. It differs from hypertrophy, which is an increase in bulk without an increase in the number of cells. [NIH] Hypersensitivity: Altered reactivity to an antigen, which can result in pathologic reactions upon subsequent exposure to that particular antigen. [NIH] Hypertension: Persistently high arterial blood pressure. Currently accepted threshold levels are 140 mm Hg systolic and 90 mm Hg diastolic pressure. [NIH] Hyperthyroidism: Excessive functional activity of the thyroid gland. [NIH] Hypertrophy: General increase in bulk of a part or organ, not due to tumor formation, nor to an increase in the number of cells. [NIH] Hyperuricemia: A buildup of uric acid (a byproduct of metabolism) in the blood; a side effect of some anticancer drugs. [NIH] Hypoglossal Nerve: The 12th cranial nerve. The hypoglossal nerve originates in the hypoglossal nucleus of the medulla and supplies motor innervation to all of the muscles of the tongue except the palatoglossus (which is supplied by the vagus). This nerve also contains proprioceptive afferents from the tongue muscles. [NIH] Hypoglycaemia: An abnormally diminished concentration of glucose in the blood, which may lead to tremulousness, cold sweat, piloerection, hypothermia, and headache, accompanied by irritability, confusion, hallucinations, bizarre behaviour, and ultimately, convulsions and coma. [EU] Hypogonadism: Condition resulting from or characterized by abnormally decreased functional activity of the gonads, with retardation of growth and sexual development. [NIH] Hypothalamus: Ventral part of the diencephalon extending from the region of the optic chiasm to the caudal border of the mammillary bodies and forming the inferior and lateral walls of the third ventricle. [NIH] Hypothermia: Lower than normal body temperature, especially in warm-blooded animals; in man usually accidental or unintentional. [NIH] Hypothyroidism: Deficiency of thyroid activity. In adults, it is most common in women and is characterized by decrease in basal metabolic rate, tiredness and lethargy, sensitivity to cold, and menstrual disturbances. If untreated, it progresses to full-blown myxoedema. In infants, severe hypothyroidism leads to cretinism. In juveniles, the manifestations are intermediate, with less severe mental and developmental retardation and only mild symptoms of the adult form. When due to pituitary deficiency of thyrotropin secretion it is called secondary hypothyroidism. [EU] Hypoxia: Reduction of oxygen supply to tissue below physiological levels despite adequate perfusion of the tissue by blood. [EU] Id: The part of the personality structure which harbors the unconscious instinctive desires and strivings of the individual. [NIH] Idiopathic: Describes a disease of unknown cause. [NIH] Illusion: A false interpretation of a genuine percept. [NIH] Immune Complex Diseases: Group of diseases mediated by the deposition of large soluble complexes of antigen and antibody with resultant damage to tissue. Besides serum sickness and the arthus reaction, evidence supports a pathogenic role for immune complexes in many other systemic immunologic diseases including glomerulonephritis, systemic lupus

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erythematosus and polyarteritis nodosa. [NIH] Immune response: The activity of the immune system against foreign substances (antigens). [NIH]

Immune Sera: Serum that contains antibodies. It is obtained from an animal that has been immunized either by antigen injection or infection with microorganisms containing the antigen. [NIH] Immune system: The organs, cells, and molecules responsible for the recognition and disposal of foreign ("non-self") material which enters the body. [NIH] Immune Tolerance: The specific failure of a normally responsive individual to make an immune response to a known antigen. It results from previous contact with the antigen by an immunologically immature individual (fetus or neonate) or by an adult exposed to extreme high-dose or low-dose antigen, or by exposure to radiation, antimetabolites, antilymphocytic serum, etc. [NIH] Immunity: Nonsusceptibility to the invasive or pathogenic microorganisms or to the toxic effect of antigenic substances. [NIH]

effects

of

foreign

Immunization: Deliberate stimulation of the host's immune response. Active immunization involves administration of antigens or immunologic adjuvants. Passive immunization involves administration of immune sera or lymphocytes or their extracts (e.g., transfer factor, immune RNA) or transplantation of immunocompetent cell producing tissue (thymus or bone marrow). [NIH] Immunoassay: Immunochemical assay or detection of a substance by serologic or immunologic methods. Usually the substance being studied serves as antigen both in antibody production and in measurement of antibody by the test substance. [NIH] Immunochemistry: Field of chemistry that pertains to immunological phenomena and the study of chemical reactions related to antigen stimulation of tissues. It includes physicochemical interactions between antigens and antibodies. [NIH] Immunodeficiency: The decreased ability of the body to fight infection and disease. [NIH] Immunofluorescence: A technique for identifying molecules present on the surfaces of cells or in tissues using a highly fluorescent substance coupled to a specific antibody. [NIH] Immunogen: A substance that is capable of causing antibody formation. [NIH] Immunogenic: Producing immunity; evoking an immune response. [EU] Immunoglobulin: A protein that acts as an antibody. [NIH] Immunologic: The ability of the antibody-forming system to recall a previous experience with an antigen and to respond to a second exposure with the prompt production of large amounts of antibody. [NIH] Immunology: The study of the body's immune system. [NIH] Immunosuppressive: Describes the ability to lower immune system responses. [NIH] Immunosuppressive therapy: Therapy used to decrease the body's immune response, such as drugs given to prevent transplant rejection. [NIH] Immunotherapy: Manipulation of the host's immune system in treatment of disease. It includes both active and passive immunization as well as immunosuppressive therapy to prevent graft rejection. [NIH] Immunotoxin: An antibody linked to a toxic substance. Some immmunotoxins can bind to cancer cells and kill them. [NIH] Impairment: In the context of health experience, an impairment is any loss or abnormality of


psychological, physiological, or anatomical structure or function. [NIH] Implant radiation: A procedure in which radioactive material sealed in needles, seeds, wires, or catheters is placed directly into or near the tumor. Also called [NIH] In situ: In the natural or normal place; confined to the site of origin without invasion of neighbouring tissues. [EU] In Situ Hybridization: A technique that localizes specific nucleic acid sequences within intact chromosomes, eukaryotic cells, or bacterial cells through the use of specific nucleic acid-labeled probes. [NIH] In vitro: In the laboratory (outside the body). The opposite of in vivo (in the body). [NIH] In vivo: In the body. The opposite of in vitro (outside the body or in the laboratory). [NIH] Incision: A cut made in the body during surgery. [NIH] Incompetence: Physical or mental inadequacy or insufficiency. [EU] Incontinence: Inability to control the flow of urine from the bladder (urinary incontinence) or the escape of stool from the rectum (fecal incontinence). [NIH] Incubated: Grown in the laboratory under controlled conditions. (For instance, white blood cells can be grown in special conditions so that they attack specific cancer cells when returned to the body.) [NIH] Incubation: The development of an infectious disease from the entrance of the pathogen to the appearance of clinical symptoms. [EU] Incubation period: The period of time likely to elapse between exposure to the agent of the disease and the onset of clinical symptoms. [NIH] Indicative: That indicates; that points out more or less exactly; that reveals fairly clearly. [EU] Induction: The act or process of inducing or causing to occur, especially the production of a specific morphogenetic effect in the developing embryo through the influence of evocators or organizers, or the production of anaesthesia or unconsciousness by use of appropriate agents. [EU] Infancy: The period of complete dependency prior to the acquisition of competence in walking, talking, and self-feeding. [NIH] 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] Inflammatory bowel disease: A general term that refers to the inflammation of the colon and rectum. Inflammatory bowel disease includes ulcerative colitis and Crohn's disease. [NIH]

Ingestion: Taking into the body by mouth [NIH]

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Inhalation: The drawing of air or other substances into the lungs. [EU] Initiator: A chemically reactive substance which may cause cell changes if ingested, inhaled or absorbed into the body; the substance may thus initiate a carcinogenic process. [NIH] Inner ear: The labyrinth, comprising the vestibule, cochlea, and semicircular canals. [NIH] Innervation: 1. The distribution or supply of nerves to a part. 2. The supply of nervous energy or of nerve stimulus sent to a part. [EU] Inotropic: Affecting the force or energy of muscular contractions. [EU] Insight: The capacity to understand one's own motives, to be aware of one's own psychodynamics, to appreciate the meaning of symbolic behavior. [NIH] Insulator: Material covering the metal conductor of the lead. It is usually polyurethane or silicone. [NIH] Insulin: A protein hormone secreted by beta cells of the pancreas. Insulin plays a major role in the regulation of glucose metabolism, generally promoting the cellular utilization of glucose. It is also an important regulator of protein and lipid metabolism. Insulin is used as a drug to control insulin-dependent diabetes mellitus. [NIH] Insulin-dependent diabetes mellitus: A disease characterized by high levels of blood glucose resulting from defects in insulin secretion, insulin action, or both. Autoimmune, genetic, and environmental factors are involved in the development of type I diabetes. [NIH] Intercostal: Situated between the ribs. [EU] Interferon: A biological response modifier (a substance that can improve the body's natural response to disease). Interferons interfere with the division of cancer cells and can slow tumor growth. There are several types of interferons, including interferon-alpha, -beta, and gamma. These substances are normally produced by the body. They are also made in the laboratory for use in treating cancer and other diseases. [NIH] Interferon-alpha: One of the type I interferons produced by peripheral blood leukocytes or lymphoblastoid cells when exposed to live or inactivated virus, double-stranded RNA, or bacterial products. It is the major interferon produced by virus-induced leukocyte cultures and, in addition to its pronounced antiviral activity, it causes activation of NK cells. [NIH] Interleukin-1: A soluble factor produced by monocytes, macrophages, and other cells which activates T-lymphocytes and potentiates their response to mitogens or antigens. IL-1 consists of two distinct forms, IL-1 alpha and IL-1 beta which perform the same functions but are distinct proteins. The biological effects of IL-1 include the ability to replace macrophage requirements for T-cell activation. The factor is distinct from interleukin-2. [NIH] Interleukin-12: A heterodimeric cytokine that stimulates the production of interferon gamma from T-cells and natural killer cells, and also induces differentiation of Th1 helper cells. It is an initiator of cell-mediated immunity. [NIH] Interleukin-18: Cytokine which resembles IL-1 structurally and IL-12 functionally. It enhances the cytotoxic activity of NK cells and CTLs, and appears to play a role both as neuroimmunomodulator and in the induction of mucosal immunity. [NIH] Interleukin-2: Chemical mediator produced by activated T lymphocytes and which regulates the proliferation of T cells, as well as playing a role in the regulation of NK cell activity. [NIH] Interleukin-4: Soluble factor produced by activated T-lymphocytes that causes proliferation and differentiation of B-cells. Interleukin-4 induces the expression of class II major histocompatibility complex and Fc receptors on B-cells. It also acts on T-lymphocytes, mast cell lines, and several other hematopoietic lineage cells including granulocyte,


megakaryocyte, and erythroid precursors, as well as macrophages. [NIH] Intermittent: Occurring at separated intervals; having periods of cessation of activity. [EU] Internal radiation: A procedure in which radioactive material sealed in needles, seeds, wires, or catheters is placed directly into or near the tumor. Also called brachytherapy, implant radiation, or interstitial radiation therapy. [NIH] Interstitial: Pertaining to or situated between parts or in the interspaces of a tissue. [EU] Intestinal: Having to do with the intestines. [NIH] Intestine: A long, tube-shaped organ in the abdomen that completes the process of digestion. There is both a large intestine and a small intestine. Also called the bowel. [NIH] Intoxication: Poisoning, the state of being poisoned. [EU] Intracellular: Inside a cell. [NIH] Intracellular Membranes: Membranes of subcellular structures. [NIH] Intracranial Hemorrhages: Bleeding within the intracranial cavity, including hemorrhages in the brain and within the cranial epidural, subdural, and subarachnoid spaces. [NIH] Intracranial Hypertension: Increased pressure within the cranial vault. This may result from several conditions, including hydrocephalus; brain edema; intracranial masses; severe systemic hypertension; pseudotumor cerebri; and other disorders. [NIH] Intracranial Pressure: Pressure within the cranial cavity. It is influenced by brain mass, the circulatory system, CSF dynamics, and skull rigidity. [NIH] Intraocular: Within the eye. [EU] Intravenous: IV. Into a vein. [NIH] Intrinsic: Situated entirely within or pertaining exclusively to a part. [EU] Invasive: 1. Having the quality of invasiveness. 2. Involving puncture or incision of the skin or insertion of an instrument or foreign material into the body; said of diagnostic techniques. [EU]

Involuntary: Reaction occurring without intention or volition. [NIH] Ion 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] Ionizing: Radiation comprising charged particles, e. g. electrons, protons, alpha-particles, etc., having sufficient kinetic energy to produce ionization by collision. [NIH] Ions: An atom or group of atoms that have a positive or negative electric charge due to a gain (negative charge) or loss (positive charge) of one or more electrons. Atoms with a positive charge are known as cations; those with a negative charge are anions. [NIH] Irradiation: The use of high-energy radiation from x-rays, neutrons, and other sources to kill cancer cells and shrink tumors. Radiation may come from a machine outside the body (external-beam radiation therapy) or from materials called radioisotopes. Radioisotopes produce radiation and can be placed in or near the tumor or in the area near cancer cells. This type of radiation treatment is called internal radiation therapy, implant radiation, interstitial radiation, or brachytherapy. Systemic radiation therapy uses a radioactive substance, such as a radiolabeled monoclonal antibody, that circulates throughout the body. Irradiation is also called radiation therapy, radiotherapy, and x-ray therapy. [NIH] Ischemia: Deficiency of blood in a part, due to functional constriction or actual obstruction of a blood vessel. [EU]

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Ischemic stroke: A condition in which the blood supply to part of the brain is cut off. Also called "plug-type" strokes. Blocked arteries starve areas of the brain controlling sight, speech, sensation, and movement so that these functions are partially or completely lost. Ischemic stroke is the most common type of stroke, accounting for 80 percent of all strokes. Most ischemic strokes are caused by a blood clot called a thrombus, which blocks blood flow in the arteries feeding the brain, usually the carotid artery in the neck, the major vessel bringing blood to the brain. When it becomes blocked, the risk of stroke is very high. [NIH] Joint: The point of contact between elements of an animal skeleton with the parts that surround and support it. [NIH] Kb: A measure of the length of DNA fragments, 1 Kb = 1000 base pairs. The largest DNA fragments are up to 50 kilobases long. [NIH] Kinetic: Pertaining to or producing motion. [EU] Labile: 1. Gliding; moving from point to point over the surface; unstable; fluctuating. 2. Chemically unstable. [EU] Labyrinth: The internal ear; the essential part of the organ of hearing. It consists of an osseous and a membranous portion. [NIH] Lacrimal: Pertaining to the tears. [EU] Lag: The time elapsing between application of a stimulus and the resulting reaction. [NIH] 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] Language Disorders: Conditions characterized by deficiencies of comprehension or expression of written and spoken forms of language. These include acquired and developmental disorders. [NIH] Large Intestine: The part of the intestine that goes from the cecum to the rectum. The large intestine absorbs water from stool and changes it from a liquid to a solid form. The large intestine is 5 feet long and includes the appendix, cecum, colon, and rectum. Also called colon. [NIH] Laryngeal: Having to do with the larynx. [NIH] Laryngeal Muscles: The intrinsic muscles of the larynx are the aryepiglottic(us), arytenoid(eus), cricoarytenoid(eus), cricothyroid(eus), thyroarytenoid(eus), thyroepiglottic(us), and vocal(is). [NIH] Laryngoscopy: Examination, therapy, or surgery of the interior of the larynx performed with a specially designed endoscope. [NIH] Larynx: An irregularly shaped, musculocartilaginous tubular structure, lined with mucous membrane, located at the top of the trachea and below the root of the tongue and the hyoid bone. It is the essential sphincter guarding the entrance into the trachea and functioning secondarily as the organ of voice. [NIH] Latent: Phoria which occurs at one distance or another and which usually has no troublesome effect. [NIH] Lectin: A complex molecule that has both protein and sugars. Lectins are able to bind to the outside of a cell and cause biochemical changes in it. Lectins are made by both animals and plants. [NIH] Lens: The transparent, double convex (outward curve on both sides) structure suspended between the aqueous and vitreous; helps to focus light on the retina. [NIH] Lentivirus: A genus of the family Retroviridae consisting of non-oncogenic retroviruses that


produce multi-organ diseases characterized by long incubation periods and persistent infection. Lentiviruses are unique in that they contain open reading frames (ORFs) between the pol and env genes and in the 3' env region. Five serogroups are recognized, reflecting the mammalian hosts with which they are associated. HIV-1 is the type species. [NIH] Lesion: An area of abnormal tissue change. [NIH] Lethal: Deadly, fatal. [EU] Lethargy: Abnormal drowsiness or stupor; a condition of indifference. [EU] Leucocyte: All the white cells of the blood and their precursors (myeloid cell series, lymphoid cell series) but commonly used to indicate granulocytes exclusive of lymphocytes. [NIH]

Leukaemia: An acute or chronic disease of unknown cause in man and other warm-blooded animals that involves the blood-forming organs, is characterized by an abnormal increase in the number of leucocytes in the tissues of the body with or without a corresponding increase of those in the circulating blood, and is classified according of the type leucocyte most prominently involved. [EU] Leukemia: Cancer of blood-forming tissue. [NIH] Leukocytes: White blood cells. These include granular leukocytes (basophils, eosinophils, and neutrophils) as well as non-granular leukocytes (lymphocytes and monocytes). [NIH] Leukoencephalopathy: A condition with spongy holes in the brain's white matter. [NIH] Library Services: Services offered to the library user. They include reference and circulation. [NIH]

Ligament: A band of fibrous tissue that connects bones or cartilages, serving to support and strengthen joints. [EU] Ligands: A RNA simulation method developed by the MIT. [NIH] Linkage: The tendency of two or more genes in the same chromosome to remain together from one generation to the next more frequently than expected according to the law of independent assortment. [NIH] Lip: Either of the two fleshy, full-blooded margins of the mouth. [NIH] Lipid: Fat. [NIH] Liver: A large, glandular organ located in the upper abdomen. The liver cleanses the blood and aids in digestion by secreting bile. [NIH] Liver Neoplasms: Tumors or cancer of the liver. [NIH] Lobe: A portion of an organ such as the liver, lung, breast, or brain. [NIH] Localization: The process of determining or marking the location or site of a lesion or disease. May also refer to the process of keeping a lesion or disease in a specific location or site. [NIH] Localized: Cancer which has not metastasized yet. [NIH] Locomotion: Movement or the ability to move from one place or another. It can refer to humans, vertebrate or invertebrate animals, and microorganisms. [NIH] 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] Lower Esophageal Sphincter: The muscle between the esophagus and stomach. When a person swallows, this muscle relaxes to let food pass from the esophagus to the stomach. It stays closed at other times to keep stomach contents from flowing back into the esophagus. [NIH]

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Lucida: An instrument, invented by Wollaton, consisting essentially of a prism or a mirror through which an object can be viewed so as to appear on a plane surface seen in direct view and on which the outline of the object may be traced. [NIH] Luciferase: Any one of several enzymes that catalyze the bioluminescent reaction in certain marine crustaceans, fish, bacteria, and insects. The enzyme is a flavoprotein; it oxidizes luciferins to an electronically excited compound that emits energy in the form of light. The color of light emitted varies with the organism. The firefly enzyme is a valuable reagent for measurement of ATP concentration. (Dorland, 27th ed) EC 1.13.12.-. [NIH] Lupus: A form of cutaneous tuberculosis. It is seen predominantly in women and typically involves the nasal, buccal, and conjunctival mucosa. [NIH] Luxation: The displacement of the particular surface of a bone from its normal joint, without fracture. [NIH] Lymph: The almost colorless fluid that travels through the lymphatic system and carries cells that help fight infection and disease. [NIH] Lymph node: A rounded mass of lymphatic tissue that is surrounded by a capsule of connective tissue. Also known as a lymph gland. Lymph nodes are spread out along lymphatic vessels and contain many lymphocytes, which filter the lymphatic fluid (lymph). [NIH]

Lymphatic: The tissues and organs, including the bone marrow, spleen, thymus, and lymph nodes, that produce and store cells that fight infection and disease. [NIH] Lymphatic system: The tissues and organs that produce, store, and carry white blood cells that fight infection and other diseases. This system includes the bone marrow, spleen, thymus, lymph nodes and a network of thin tubes that carry lymph and white blood cells. These tubes branch, like blood vessels, into all the tissues of the body. [NIH] Lymphoblastic: One of the most aggressive types of non-Hodgkin lymphoma. [NIH] 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] Lymphocyte Subsets: A classification of lymphocytes based on structurally or functionally different populations of cells. [NIH] Lymphoid: Referring to lymphocytes, a type of white blood cell. Also refers to tissue in which lymphocytes develop. [NIH] Lymphokines: Soluble protein factors generated by activated lymphocytes that affect other cells, primarily those involved in cellular immunity. [NIH] Lymphoma: A general term for various neoplastic diseases of the lymphoid tissue. [NIH] Lysine: An essential amino acid. It is often added to animal feed. [NIH] Macrolides: A group of organic compounds that contain a macrocyclic lactone ring linked glycosidically to one or more sugar moieties. [NIH] Macrophage: A type of white blood cell that surrounds and kills microorganisms, removes dead cells, and stimulates the action of other immune system cells. [NIH] Maintenance therapy: Treatment that is given to help a primary (original) treatment keep working. Maintenance therapy is often given to help keep cancer in remission. [NIH] Major Histocompatibility Complex: The genetic region which contains the loci of genes which determine the structure of the serologically defined (SD) and lymphocyte-defined (LD) transplantation antigens, genes which control the structure of the immune responseassociated (Ia) antigens, the immune response (Ir) genes which control the ability of an


animal to respond immunologically to antigenic stimuli, and genes which determine the structure and/or level of the first four components of complement. [NIH] Malabsorption: Impaired intestinal absorption of nutrients. [EU] Malformation: A morphologic developmental process. [EU]

defect

resulting

from

an

intrinsically

abnormal

Malignancy: A cancerous tumor that can invade and destroy nearby tissue and spread to other parts of the body. [NIH] Malignant: Cancerous; a growth with a tendency to invade and destroy nearby tissue and spread to other parts of the body. [NIH] Malnutrition: A condition caused by not eating enough food or not eating a balanced diet. [NIH]

Mandible: The largest and strongest bone of the face constituting the lower jaw. It supports the lower teeth. [NIH] Mandibular Condyle: The posterior process on the ramus of the mandible composed of two parts: a superior part, the articular portion, and an inferior part, the condylar neck. [NIH] Mania: Excitement of psychotic proportions manifested by mental and physical hyperactivity, disorganization of behaviour, and elevation of mood. [EU] Manic: Affected with mania. [EU] Manifest: Being the part or aspect of a phenomenon that is directly observable : concretely expressed in behaviour. [EU] Mastication: The act and process of chewing and grinding food in the mouth. [NIH] Matrilysin: The smallest member of the matrix metalloproteinases. It plays a role in tumor progression. EC 3.4.24.23. [NIH] Matrix metalloproteinase: A member of a group of enzymes that can break down proteins, such as collagen, that are normally found in the spaces between cells in tissues (i.e., extracellular matrix proteins). Because these enzymes need zinc or calcium atoms to work properly, they are called metalloproteinases. Matrix metalloproteinases are involved in wound healing, angiogenesis, and tumor cell metastasis. [NIH] Mecamylamine: A nicotinic antagonist that is well absorbed from the gastrointestinal tract and crosses the blood-brain barrier. Mecamylamine has been used as a ganglionic blocker in treating hypertension, but, like most ganglionic blockers, is more often used now as a research tool. [NIH] Mediastinum: The area between the lungs. The organs in this area include the heart and its large blood vessels, the trachea, the esophagus, the bronchi, and lymph nodes. [NIH] Mediate: Indirect; accomplished by the aid of an intervening medium. [EU] Mediator: An object or substance by which something is mediated, such as (1) a structure of the nervous system that transmits impulses eliciting a specific response; (2) a chemical substance (transmitter substance) that induces activity in an excitable tissue, such as nerve or muscle; or (3) a substance released from cells as the result of the interaction of antigen with antibody or by the action of antigen with a sensitized lymphocyte. [EU] MEDLINE: An online database of MEDLARS, the computerized bibliographic Medical Literature Analysis and Retrieval System of the National Library of Medicine. [NIH] Medullary: Pertaining to the marrow or to any medulla; resembling marrow. [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

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characteristic of the somatic cells of the species. [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] Memory: Complex mental function having four distinct phases: (1) memorizing or learning, (2) retention, (3) recall, and (4) recognition. Clinically, it is usually subdivided into immediate, recent, and remote memory. [NIH] Meninges: The three membranes that cover and protect the brain and spinal cord. [NIH] Menstruation: The normal physiologic discharge through the vagina of blood and mucosal tissues from the nonpregnant uterus. [NIH] Mental Disorders: Psychiatric illness or diseases manifested by breakdowns in the adaptational process expressed primarily as abnormalities of thought, feeling, and behavior producing either distress or impairment of function. [NIH] Mental Fatigue: Fatigue arising in consequence of mental effort. [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]

Mentors: Senior professionals who provide guidance, direction and support to those persons desirous of improvement in academic positions, administrative positions or other career development situations. [NIH] Mercury: A silver metallic element that exists as a liquid at room temperature. It has the atomic symbol Hg (from hydrargyrum, liquid silver), atomic number 80, and atomic weight 200.59. Mercury is used in many industrial applications and its salts have been employed therapeutically as purgatives, antisyphilitics, disinfectants, and astringents. It can be absorbed through the skin and mucous membranes which leads to mercury poisoning. Because of its toxicity, the clinical use of mercury and mercurials is diminishing. [NIH] 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] 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] 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] 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] Mineralization: The action of mineralizing; the state of being mineralized. [EU] Mineralocorticoids: A group of corticosteroids primarily associated with the regulation of water and electrolyte balance. This is accomplished through the effect on ion transport in renal tubules, resulting in retention of sodium and loss of potassium. Mineralocorticoid secretion is itself regulated by plasma volume, serum potassium, and angiotensin II. [NIH] 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] Modification: A change in an organism, or in a process in an organism, that is acquired from its own activity or environment. [NIH] Molecular: Of, pertaining to, or composed of molecules : a very small mass of matter. [EU] 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] Monocytes: Large, phagocytic mononuclear leukocytes produced in the vertebrate bone marrow and released into the blood; contain a large, oval or somewhat indented nucleus surrounded by voluminous cytoplasm and numerous organelles. [NIH] Mononuclear: A cell with one nucleus. [NIH] Monophosphate: So called second messenger for neurotransmitters and hormones. [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] Morphology: The science of the form and structure of organisms (plants, animals, and other forms of life). [NIH]

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Motility: The ability to move spontaneously. [EU] Motion Sickness: Sickness caused by motion, as sea sickness, train sickness, car sickness, and air sickness. [NIH] Motor Activity: The physical activity of an organism as a behavioral phenomenon. [NIH] Motor Endplate: The specialized postsynaptic region of a muscle cell. The motor endplate is immediately across the synaptic cleft from the presynaptic axon terminal. Among its anatomical specializations are junctional folds which harbor a high density of cholinergic receptors. [NIH] Motor nerve: An efferent nerve conveying an impulse that excites muscular contraction. [NIH]

Movement Disorders: Syndromes which feature dyskinesias as a cardinal manifestation of the disease process. Included in this category are degenerative, hereditary, post-infectious, medication-induced, post-inflammatory, and post-traumatic conditions. [NIH] Mucinous: Containing or resembling mucin, the main compound in mucus. [NIH] Mucosa: A mucous membrane, or tunica mucosa. [EU] Multidrug resistance: Adaptation of tumor cells to anticancer drugs in ways that make the drugs less effective. [NIH] Multiple sclerosis: A disorder of the central nervous system marked by weakness, numbness, a loss of muscle coordination, and problems with vision, speech, and bladder control. Multiple sclerosis is thought to be an autoimmune disease in which the body's immune system destroys myelin. Myelin is a substance that contains both protein and fat (lipid) and serves as a nerve insulator and helps in the transmission of nerve signals. [NIH] Muscarinic Agonists: Drugs that bind to and activate muscarinic cholinergic receptors (receptors, muscarinic). Muscarinic agonists are most commonly used when it is desirable to increase smooth muscle tone, especially in the GI tract, urinary bladder and the eye. They may also be used to reduce heart rate. [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 Hypertonia: Abnormal increase in skeletal or smooth muscle tone. Skeletal muscle hypertonicity may be associated with pyramidal tract lesions or basal ganglia diseases. [NIH] Muscle relaxant: An agent that specifically aids in reducing muscle tension, as those acting at the polysynaptic neurons of motor nerves (e.g. meprobamate) or at the myoneural junction (curare and related compounds). [EU] Muscle Relaxation: That phase of a muscle twitch during which a muscle returns to a resting position. [NIH] 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 Diseases: Acquired, familial, and congenital disorders of skeletal muscle and smooth muscle. [NIH] Muscular Dystrophies: A general term for a group of inherited disorders which are characterized by progressive degeneration of skeletal muscles. [NIH]


Musculoskeletal System: Themuscles, bones, and cartilage of the body. [NIH] 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] Myasthenia: Muscular debility; any constitutional anomaly of muscle. [EU] Mycophenolate mofetil: A drug that is being studied for its effectiveness in preventing graft-versus-host disease and autoimmune disorders. [NIH] Mydriatic: 1. Dilating the pupil. 2. Any drug that dilates the pupil. [EU] Myelin: The fatty substance that covers and protects nerves. [NIH] Myocarditis: Inflammation of the myocardium; inflammation of the muscular walls of the heart. [EU] Myocardium: The muscle tissue of the heart composed of striated, involuntary muscle known as cardiac muscle. [NIH] Myofibrils: Highly organized bundles of actin, myosin, and other proteins in the cytoplasm of skeletal and cardiac muscle cells that contract by a sliding filament mechanism. [NIH] Myopathy: Any disease of a muscle. [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] Myositis: Inflammation of a voluntary muscle. [EU] Myotonia: Prolonged failure of muscle relaxation after contraction. This may occur after voluntary contractions, muscle percussion, or electrical stimulation of the muscle. Myotonia is a characteristic feature of myotonic disorders. [NIH] 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] Nasalis: A small fly whose larvae are parasites of the horse, the adult female fly depositing them into and around the nostrils, from where they later migrate to the pharynx or larynx of their host. [NIH] Natural killer cells: NK cells. A type of white blood cell that contains granules with enzymes that can kill tumor cells or microbial cells. Also called large granular lymphocytes (LGL). [NIH] Nausea: An unpleasant sensation in the stomach usually accompanied by the urge to vomit. Common causes are early pregnancy, sea and motion sickness, emotional stress, intense pain, food poisoning, and various enteroviruses. [NIH] NCI: National Cancer Institute. NCI, part of the National Institutes of Health of the United States Department of Health and Human Services, is the federal government's principal agency for cancer research. NCI conducts, coordinates, and funds cancer research, training, health information dissemination, and other programs with respect to the cause, diagnosis, prevention, and treatment of cancer. Access the NCI Web site at http://cancer.gov. [NIH] Nebramycin: A complex of antibiotic substances produced by Streptomyces tenebrarius. [NIH]

Necrosis: A pathological process caused by the progressive degradative action of enzymes

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that is generally associated with severe cellular trauma. It is characterized by mitochondrial swelling, nuclear flocculation, uncontrolled cell lysis, and ultimately cell death. [NIH] Need: A state of tension or dissatisfaction felt by an individual that impels him to action toward a goal he believes will satisfy the impulse. [NIH] Neonatal: Pertaining to the first four weeks after birth. [EU] 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] Neostigmine: A cholinesterase inhibitor used in the treatment of myasthenia gravis and to reverse the effects of muscle relaxants such as gallamine and tubocurarine. Neostigmine, unlike physostigmine, does not cross the blood-brain barrier. [NIH] Nerve: A cordlike structure of nervous tissue that connects parts of the nervous system with other tissues of the body and conveys nervous impulses to, or away from, these tissues. [NIH] Nervous System: The entire nerve apparatus composed of the brain, spinal cord, nerves and ganglia. [NIH] Nervous System Diseases: Diseases of the central and peripheral nervous system. This includes disorders of the brain, spinal cord, cranial nerves, peripheral nerves, nerve roots, autonomic nervous system, neuromuscular junction, and muscle. [NIH] Networks: Pertaining to a nerve or to the nerves, a meshlike structure of interlocking fibers or strands. [NIH] Neural: 1. Pertaining to a nerve or to the nerves. 2. Situated in the region of the spinal axis, as the neutral arch. [EU] Neural tube defects: These defects include problems stemming from fetal development of the spinal cord, spine, brain, and skull, and include birth defects such as spina bifida, anencephaly, and encephalocele. Neural tube defects occur early in pregnancy at about 4 to 6 weeks, usually before a woman knows she is pregnant. Many babies with neural tube defects have difficulty walking and with bladder and bowel control. [NIH] Neuregulins: A family of peptides originally found as factors that stimulate the phosphorylation of the erbB-2 receptor. Multiple variant forms of neuregulins occur due to alternative splicing of their mRNAs. The neuregulins include products from the three known genes (NGR1, NGR2 and NGR3). [NIH] Neuroanatomy: Study of the anatomy of the nervous system as a specialty or discipline. [NIH]

Neurodegenerative Diseases: Hereditary and sporadic conditions which are characterized by progressive nervous system dysfunction. These disorders are often associated with atrophy of the affected central or peripheral nervous system structures. [NIH] Neuroeffector Junction: The synapse between a neuron (presynaptic) and an effector cell other than another neuron (postsynaptic). Neuroeffector junctions include synapses onto muscles and onto secretory cells. [NIH] Neuroendocrine: Having to do with the interactions between the nervous system and the endocrine system. Describes certain cells that release hormones into the blood in response to stimulation of the nervous system. [NIH] Neurogenic: Loss of bladder control caused by damage to the nerves controlling the bladder. [NIH] Neurologic: Having to do with nerves or the nervous system. [NIH] Neurologist: A doctor who specializes in the diagnosis and treatment of disorders of the


nervous system. [NIH] Neurology: A medical specialty concerned with the study of the structures, functions, and diseases of the nervous system. [NIH] Neuromuscular: Pertaining to muscles and nerves. [EU] Neuromuscular Blockade: The intentional interruption of transmission at the neuromuscular junction by external agents, usually neuromuscular blocking agents. It is distinguished from nerve block in which nerve conduction is interrupted rather than neuromuscular transmission. Neuromuscular blockade is commonly used to produce muscle relaxation as an adjunct to anesthesia during surgery and other medical procedures. It is also often used as an experimental manipulation in basic research. It is not strictly speaking anesthesia but is grouped here with anesthetic techniques. The failure of neuromuscular transmission as a result of pathological processes is not included here. [NIH] Neuromuscular Diseases: A general term encompassing lower motor neuron disease; peripheral nervous system diseases; and certain muscular diseases. Manifestations include muscle weakness; fasciculation; muscle atrophy; spasm; myokymia; muscle hypertonia, myalgias, and musclehypotonia. [NIH] Neuromuscular Junction: The synapse between a neuron and a muscle. [NIH] Neuromuscular Junction Diseases: Conditions characterized by impaired transmission of impulses at the neuromuscular junction. This may result from disorders that affect receptor function, pre- or postsynaptic membrane function, or acetylcholinesteraseactivity. The majority of diseases in this category are associated with autoimmune, toxic, or inherited conditions. [NIH] Neuronal: Pertaining to a neuron or neurons (= conducting cells of the nervous system). [EU] Neurons: The basic cellular units of nervous tissue. Each neuron consists of a body, an axon, and dendrites. Their purpose is to receive, conduct, and transmit impulses in the nervous system. [NIH] Neuropathy: A problem in any part of the nervous system except the brain and spinal cord. Neuropathies can be caused by infection, toxic substances, or disease. [NIH] Neuropeptide: A member of a class of protein-like molecules made in the brain. Neuropeptides consist of short chains of amino acids, with some functioning as neurotransmitters and some functioning as hormones. [NIH] Neuropharmacology: The branch of pharmacology dealing especially with the action of drugs upon various parts of the nervous system. [NIH] Neurophysiology: The scientific discipline concerned with the physiology of the nervous system. [NIH] Neurosyphilis: A late form of syphilis that affects the brain and may lead to dementia and death. [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] 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

Dictionary 221

unstable when isolated from the nucleus, undergoing beta decay. Slow, thermal, epithermal, and fast neutrons refer to the energy levels with which the neutrons are ejected from heavier nuclei during their decay. [NIH] Neutrophil: A type of white blood cell. [NIH] Neutrophil Collagenase: A member of the matrix metalloproteinases that cleaves triplehelical collagens types I, II, and III. EC 3.4.24.34. [NIH] Niacin: Water-soluble vitamin of the B complex occurring in various animal and plant tissues. Required by the body for the formation of coenzymes NAD and NADP. Has pellagra-curative, vasodilating, and antilipemic properties. [NIH] Nicotine: Nicotine is highly toxic alkaloid. It is the prototypical agonist at nicotinic cholinergic receptors where it dramatically stimulates neurons and ultimately blocks synaptic transmission. Nicotine is also important medically because of its presence in tobacco smoke. [NIH] Nicotinic Agonists: Drugs that bind to and activate nicotinic cholinergic receptors (receptors, nicotinic). Nicotinic agonists act at postganglionic nicotinic receptors, at neuroeffector junctions in the peripheral nervous system, and at nicotinic receptors in the central nervous system. Agents that function as neuromuscular depolarizing blocking agents are included here because they activate nicotinic receptors, although they are used clinically to block nicotinic transmission. [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] Nonverbal Communication: Transmission of emotions, ideas, and attitudes between individuals in ways other than the spoken language. [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] 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] Nucleus: A body of specialized protoplasm found in nearly all cells and containing the chromosomes. [NIH] Nystagmus: Rhythmical oscillation of the eyeballs, either pendular or jerky. [NIH] Occipital Lobe: Posterior part of the cerebral hemisphere. [NIH] Ocular: 1. Of, pertaining to, or affecting the eye. 2. Eyepiece. [EU] Oculi: Globe or ball of the eye. [NIH] Oculomotor: Cranial nerve III. It originate from the lower ventral surface of the midbrain and is classified as a motor nerve. [NIH]


Oculomotor Nerve: The 3d cranial nerve. The oculomotor nerve sends motor fibers to the levator muscles of the eyelid and to the superior rectus, inferior rectus, and inferior oblique muscles of the eye. It also sends parasympathetic efferents (via the ciliary ganglion) to the muscles controlling pupillary constriction and accommodation. The motor fibers originate in the oculomotor nuclei of the midbrain. [NIH] Odour: A volatile emanation that is perceived by the sense of smell. [EU] Odynophagia: A painful condition of the esophagus. [NIH] Oligo: Chemical and mineral elements that exist in minimal (oligo) quantities in the body, in foods, in the air, in soil; name applied to any element observed as a microconstituent of plant or animal tissue and of beneficial, harmful, or even doubtful significance. [NIH] Oncogenic: Chemical, viral, radioactive or other agent that causes cancer; carcinogenic. [NIH] Oocytes: Female germ cells in stages between the prophase of the first maturation division and the completion of the second maturation division. [NIH] Opacity: Degree of density (area most dense taken for reading). [NIH] Open Reading Frames: Reading frames where successive nucleotide triplets can be read as codons specifying amino acids and where the sequence of these triplets is not interrupted by stop codons. [NIH] Ophthalmic: Pertaining to the eye. [EU] Ophthalmoplegia: Paralysis of one or more of the ocular muscles due to disorders of the eye muscles, neuromuscular junction, supporting soft tissue, tendons, or innervation to the muscles. [NIH] Opium: The air-dried exudate from the unripe seed capsule of the opium poppy, Papaver somniferum, or its variant, P. album. It contains a number of alkaloids, but only a few morphine, codeine, and papaverine - have clinical significance. Opium has been used as an analgesic, antitussive, antidiarrheal, and antispasmodic. [NIH] Oral Health: The optimal state of the mouth and normal functioning of the organs of the mouth without evidence of disease. [NIH] Orbicularis: A thin layer of fibers that originates at the posterior lacrimal crest and passes outward and forward, dividing into two slips which surround the canaliculi. [NIH] Orbit: One of the two cavities in the skull which contains an eyeball. Each eye is located in a bony socket or orbit. [NIH] Orbital: Pertaining to the orbit (= the bony cavity that contains the eyeball). [EU] Orofacial: Of or relating to the mouth and face. [EU] 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] Osteogenesis: The histogenesis of bone including ossification. It occurs continuously but particularly in the embryo and child and during fracture repair. [NIH] Osteogenesis Imperfecta: A collagen disorder resulting from defective biosynthesis of type I collagen and characterized by brittle, osteoporotic, and easily fractured bones. It may also present with blue sclerae, loose joints, and imperfect dentin formation. There are four major types, I-IV. [NIH]

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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]

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] Ovary: Either of the paired glands in the female that produce the female germ cells and secrete some of the female sex hormones. [NIH] Palate: The structure that forms the roof of the mouth. It consists of the anterior hard palate and the posterior soft palate. [NIH] Palliative: 1. Affording relief, but not cure. 2. An alleviating medicine. [EU] Palsies: Disease of the peripheral nervous system occurring usually after many years of increased lead absorption. [NIH] Palsy: Disease of the peripheral nervous system occurring usually after many years of increased lead absorption. [NIH] Pancreas: A mixed exocrine and endocrine gland situated transversely across the posterior abdominal wall in the epigastric and hypochondriac regions. The endocrine portion is comprised of the Islets of Langerhans, while the exocrine portion is a compound acinar gland that secretes digestive enzymes. [NIH] Pancreatic: Having to do with the pancreas. [NIH] Pancreatic Juice: The fluid containing digestive enzymes secreted by the pancreas in response to food in the duodenum. [NIH] Papain: A proteolytic enzyme obtained from Carica papaya. It is also the name used for a purified mixture of papain and chymopapain that is used as a topical enzymatic debriding agent. EC 3.4.22.2. [NIH] Paralysis: Loss of ability to move all or part of the body. [NIH] Paraneoplastic syndrome: A group of symptoms that may develop when substances released by some cancer cells disrupt the normal function of surrounding cells and tissue. [NIH]

Parathyroid: 1. Situated beside the thyroid gland. 2. One of the parathyroid glands. 3. A sterile preparation of the water-soluble principle(s) of the parathyroid glands, ad-ministered parenterally as an antihypocalcaemic, especially in the treatment of acute hypoparathyroidism with tetany. [EU] Parathyroid Glands: Two small paired endocrine glands in the region of the thyroid gland. They secrete parathyroid hormone and are concerned with the metabolism of calcium and phosphorus. [NIH] 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] Partial remission: The shrinking, but not complete disappearance, of a tumor in response to therapy. Also called partial response. [NIH]


Partnership Practice: A voluntary contract between two or more doctors who may or may not share responsibility for the care of patients, with proportional sharing of profits and losses. [NIH] Patch: A piece of material used to cover or protect a wound, an injured part, etc.: a patch over the eye. [NIH] Pathogen: Any disease-producing microorganism. [EU] Pathogenesis: The cellular events and reactions that occur in the development of disease. [NIH]

Pathologic: 1. Indicative of or caused by a morbid condition. 2. Pertaining to pathology (= branch of medicine that treats the essential nature of the disease, especially the structural and functional changes in tissues and organs of the body caused by the disease). [EU] Pathologic Processes: The abnormal mechanisms and forms involved in the dysfunctions of tissues and organs. [NIH] Pathophysiology: Altered functions in an individual or an organ due to disease. [NIH] Patient Advocacy: Promotion and protection of the rights of patients, frequently through a legal process. [NIH] Patient Education: The teaching or training of patients concerning their own health needs. [NIH]

Pemphigus: Group of chronic blistering diseases characterized histologically by acantholysis and blister formation within the epidermis. [NIH] Penicillamine: 3-Mercapto-D-valine. The most characteristic degradation product of the penicillin antibiotics. It is used as an antirheumatic and as a chelating agent in Wilson's disease. [NIH] Penicillin: An antibiotic drug used to treat infection. [NIH] Pepsin: An enzyme made in the stomach that breaks down proteins. [NIH] Peptic: Pertaining to pepsin or to digestion; related to the action of gastric juices. [EU] Peptide: Any compound consisting of two or more amino acids, the building blocks of proteins. Peptides are combined to make proteins. [NIH] Peptide T: N-(N-(N(2)-(N-(N-(N-(N-D-Alanyl L-seryl)-L-threonyl)-L-threonyl) L-threonyl)L-asparaginyl)-L-tyrosyl) L-threonine. Octapeptide sharing sequence homology with HIV envelope protein gp120. It is potentially useful as antiviral agent in AIDS therapy. The core pentapeptide sequence, TTNYT, consisting of amino acids 4-8 in peptide T, is the HIV envelope sequence required for attachment to the CD4 receptor. [NIH] 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] Perfusion: Bathing an organ or tissue with a fluid. In regional perfusion, a specific area of the body (usually an arm or a leg) receives high doses of anticancer drugs through a blood vessel. Such a procedure is performed to treat cancer that has not spread. [NIH] Pericardium: The fibroserous sac surrounding the heart and the roots of the great vessels. [NIH]

Periodontal disease: Disease involving the supporting structures of the teeth (as the gums and periodontal membranes). [NIH]

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Perioral: Situated or occurring around the mouth. [EU] Peripheral blood: Blood circulating throughout the body. [NIH] Peripheral Nervous System: The nervous system outside of the brain and spinal cord. The peripheral nervous system has autonomic and somatic divisions. The autonomic nervous system includes the enteric, parasympathetic, and sympathetic subdivisions. The somatic nervous system includes the cranial and spinal nerves and their ganglia and the peripheral sensory receptors. [NIH] Peripheral Nervous System Diseases: Diseases of the peripheral nerves external to the brain and spinal cord, which includes diseases of the nerve roots, ganglia, plexi, autonomic nerves, sensory nerves, and motor nerves. [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] Peripheral stem cells: Immature cells found circulating in the bloodstream. New blood cells develop from peripheral stem cells. [NIH] Perivascular: Situated around a vessel. [EU] Pernicious: Tending to a fatal issue. [EU] Pernicious anemia: A type of anemia (low red blood cell count) caused by the body's inability to absorb vitamin B12. [NIH] Pharmacokinetics: Dynamic and kinetic mechanisms of exogenous chemical and drug absorption, biotransformation, distribution, release, transport, uptake, and elimination as a function of dosage, and extent and rate of metabolic processes. It includes toxicokinetics, the pharmacokinetic mechanism of the toxic effects of a substance. [NIH] Pharmacologic: Pertaining to pharmacology or to the properties and reactions of drugs. [EU] Pharyngeal Muscles: The muscles of the pharynx are the inferior, middle and superior constrictors, salpingopharyngeus, and stylopharyngeus. [NIH] Pharynx: The hollow tube about 5 inches long that starts behind the nose and ends at the top of the trachea (windpipe) and esophagus (the tube that goes to the stomach). [NIH] Phenotype: The outward appearance of the individual. It is the product of interactions between genes and between the genotype and the environment. This includes the killer phenotype, characteristic of yeasts. [NIH] Phenyl: Ingredient used in cold and flu remedies. [NIH] Phonation: The process of producing vocal sounds by means of vocal cords vibrating in an expiratory blast of air. [NIH] Phosphodiesterase: Effector enzyme that regulates the levels of a second messenger, the cyclic GMP. [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] 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] Phrenic Nerve: The motor nerve of the diaphragm. The phrenic nerve fibers originate in the cervical spinal column (mostly C4) and travel through the cervical plexus to the diaphragm. [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] Physostigmine: A cholinesterase inhibitor that is rapidly absorbed through membranes. It can be applied topically to the conjunctiva. It also can cross the blood-brain barrier and is used when central nervous system effects are desired, as in the treatment of severe anticholinergic toxicity. [NIH] Phytotoxin: A substance which is toxic for plants. [NIH] Pilot study: The initial study examining a new method or treatment. [NIH] Pipecuronium: A non-depolarizing neuromuscular blocking agent used during halothane anesthesia and obstetric and gynecologic surgery. [NIH] Pitch: The subjective awareness of the frequency or spectral distribution of a sound. [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 Exchange: Removal of plasma and replacement with various fluids, e.g., fresh frozen plasma, plasma protein fractions (PPF), albumin preparations, dextran solutions, saline. Used in treatment of autoimmune diseases, immune complex diseases, diseases of excess plasma factors, and other conditions. [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] Plasmacytoma: Any discrete, presumably solitary, mass of neoplastic plasma cells either in bone marrow or various extramedullary sites. [NIH] Plasmapheresis: Procedure whereby plasma is separated and extracted from anticoagulated whole blood and the red cells retransfused to the donor. Plasmapheresis is also employed for therapeutic use. [NIH]

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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] 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]

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] Point Mutation: A mutation caused by the substitution of one nucleotide for another. This results in the DNA molecule having a change in a single base pair. [NIH] Poisoning: A condition or physical state produced by the ingestion, injection or inhalation of, or exposure to a deleterious agent. [NIH] Pollen: The male fertilizing element of flowering plants analogous to sperm in animals. It is released from the anthers as yellow dust, to be carried by insect or other vectors, including wind, to the ovary (stigma) of other flowers to produce the embryo enclosed by the seed. The pollens of many plants are allergenic. [NIH] Polymorphism: The occurrence together of two or more distinct forms in the same population. [NIH] Polypeptide: A peptide which on hydrolysis yields more than two amino acids; called tripeptides, tetrapeptides, etc. according to the number of amino acids contained. [EU] Polysaccharide: A type of carbohydrate. It contains sugar molecules that are linked together chemically. [NIH] Polyvinyl Alcohol: A polymer prepared from polyvinyl acetates by replacement of the acetate groups with hydroxyl groups. It is used as a pharmaceutic aid and ophthalmic lubricant as well as in the manufacture of surface coatings artificial sponges, cosmetics, and other products. [NIH] Pons: The part of the central nervous system lying between the medulla oblongata and the mesencephalon, ventral to the cerebellum, and consisting of a pars dorsalis and a pars ventralis. [NIH] Posterior: Situated in back of, or in the back part of, or affecting the back or dorsal surface of the body. In lower animals, it refers to the caudal end of the body. [EU] Postmenopausal: Refers to the time after menopause. Menopause is the time in a woman's life when menstrual periods stop permanently; also called "change of life." [NIH] Postnatal: Occurring after birth, with reference to the newborn. [EU] Postoperative: After surgery. [NIH] Postsynaptic: Nerve potential generated by an inhibitory hyperpolarizing stimulation. [NIH] Post-synaptic: Nerve potential generated by an inhibitory hyperpolarizing stimulation. [NIH] Potentiates: A degree of synergism which causes the exposure of the organism to a harmful substance to worsen a disease already contracted. [NIH] Potentiation: An overall effect of two drugs taken together which is greater than the sum of the effects of each drug taken alone. [NIH]


Practice Guidelines: Directions or principles presenting current or future rules of policy for the health care practitioner to assist him in patient care decisions regarding diagnosis, therapy, or related clinical circumstances. The guidelines may be developed by government agencies at any level, institutions, professional societies, governing boards, or by the convening of expert panels. The guidelines form a basis for the evaluation of all aspects of health care and delivery. [NIH] Precursor: Something that precedes. In biological processes, a substance from which another, usually more active or mature substance is formed. In clinical medicine, a sign or symptom that heralds another. [EU] Predisposition: A latent susceptibility to disease which may be activated under certain conditions, as by stress. [EU] Prednisolone: A glucocorticoid with the general properties of the corticosteroids. It is the drug of choice for all conditions in which routine systemic corticosteroid therapy is indicated, except adrenal deficiency states. [NIH] Prednisone: A synthetic anti-inflammatory glucocorticoid derived from cortisone. It is biologically inert and converted to prednisolone in the liver. [NIH] Pregnancy Outcome: Results of conception and ensuing pregnancy, including live birth, stillbirth, spontaneous abortion, induced abortion. The outcome may follow natural or artificial insemination or any of the various reproduction techniques, such as embryo transfer or fertilization in vitro. [NIH] Presynaptic: Situated proximal to a synapse, or occurring before the synapse is crossed. [EU] Prevalence: The total number of cases of a given disease in a specified population at a designated time. It is differentiated from incidence, which refers to the number of new cases in the population at a given time. [NIH] Primary Biliary Cirrhosis: A chronic liver disease. Slowly destroys the bile ducts in the liver. This prevents release of bile. Long-term irritation of the liver may cause scarring and cirrhosis in later stages of the disease. [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] Private Practice: Practice of a health profession by an individual, offering services on a person-to-person basis, as opposed to group or partnership practice. [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] Prophase: The first phase of cell division, in which the chromosomes become visible, the nucleus starts to lose its identity, the spindle appears, and the centrioles migrate toward opposite poles. [NIH] Prophylaxis: An attempt to prevent disease. [NIH] Proprioception: The mechanism involved in the self-regulation of posture and movement through stimuli originating in the receptors imbedded in the joints, tendons, muscles, and labyrinth. [NIH]

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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 proteases (endopeptidases). [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 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] Proteolytic: 1. Pertaining to, characterized by, or promoting proteolysis. 2. An enzyme that promotes proteolysis (= the splitting of proteins by hydrolysis of the peptide bonds with formation of smaller polypeptides). [EU] Protocol: The detailed plan for a clinical trial that states the trial's rationale, purpose, drug or vaccine dosages, length of study, routes of administration, who may participate, and other aspects of trial design. [NIH] Protons: Stable elementary particles having the smallest known positive charge, found in the nuclei of all elements. The proton mass is less than that of a neutron. A proton is the nucleus of the light hydrogen atom, i.e., the hydrogen ion. [NIH] 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] Psoralen: A substance that binds to the DNA in cells and stops them from multiplying. It is being studied in the treatment of graft-versus-host disease and is used in the treatment of psoriasis and vitiligo. [NIH] Psoriasis: A common genetically determined, chronic, inflammatory skin disease characterized by rounded erythematous, dry, scaling patches. The lesions have a predilection for nails, scalp, genitalia, extensor surfaces, and the lumbosacral region. Accelerated epidermopoiesis is considered to be the fundamental pathologic feature in psoriasis. [NIH] Psychiatric: Pertaining to or within the purview of psychiatry. [EU] Psychiatry: The medical science that deals with the origin, diagnosis, prevention, and treatment of mental disorders. [NIH] Psychic: Pertaining to the psyche or to the mind; mental. [EU] Psychogenic: Produced or caused by psychic or mental factors rather than organic factors. [EU]

Psychomotor: Pertaining to motor effects of cerebral or psychic activity. [EU] Ptosis: 1. Prolapse of an organ or part. 2. Drooping of the upper eyelid from paralysis of the


third nerve or from sympathetic innervation. [EU] Puberty: The period during which the secondary sex characteristics begin to develop and the capability of sexual reproduction is attained. [EU] 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]

Pulse: The rhythmical expansion and contraction of an artery produced by waves of pressure caused by the ejection of blood from the left ventricle of the heart as it contracts. [NIH]

Pupil: The aperture in the iris through which light passes. [NIH] Purines: A series of heterocyclic compounds that are variously substituted in nature and are known also as purine bases. They include adenine and guanine, constituents of nucleic acids, as well as many alkaloids such as caffeine and theophylline. Uric acid is the metabolic end product of purine metabolism. [NIH] Purpura: Purplish or brownish red discoloration, easily visible through the epidermis, caused by hemorrhage into the tissues. [NIH] Quadriplegia: Severe or complete loss of motor function in all four limbs which may result from brain diseases; spinal cord diseases; peripheral nervous system diseases; neuromuscular diseases; or rarely muscular diseases. The locked-in syndrome is characterized by quadriplegia in combination with cranial muscle paralysis. Consciousness is spared and the only retained voluntary motor activity may be limited eye movements. This condition is usually caused by a lesion in the upper brain stem which injures the descending cortico-spinal and cortico-bulbar tracts. [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] Quiescent: Marked by a state of inactivity or repose. [EU] Radiation: Emission or propagation of electromagnetic energy (waves/rays), or the waves/rays themselves; a stream of electromagnetic particles (electrons, neutrons, protons, alpha particles) or a mixture of these. The most common source is the sun. [NIH] Radiation therapy: The use of high-energy radiation from x-rays, gamma rays, neutrons, and other sources to kill cancer cells and shrink tumors. Radiation may come from a machine outside the body (external-beam radiation therapy), or it may come from radioactive material placed in the body in the area near cancer cells (internal radiation therapy, implant radiation, or brachytherapy). Systemic radiation therapy uses a radioactive substance, such as a radiolabeled monoclonal antibody, that circulates throughout the body. Also called radiotherapy. [NIH] Radioactive: Giving off radiation. [NIH] Radioimmunoassay: Classic quantitative assay for detection of antigen-antibody reactions using a radioactively labeled substance (radioligand) either directly or indirectly to measure the binding of the unlabeled substance to a specific antibody or other receptor system. Nonimmunogenic substances (e.g., haptens) can be measured if coupled to larger carrier proteins (e.g., bovine gamma-globulin or human serum albumin) capable of inducing antibody formation. [NIH] Radiolabeled: Any compound that has been joined with a radioactive substance. [NIH]

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Radiological: Pertaining to radiodiagnostic and radiotherapeutic procedures, and interventional radiology or other planning and guiding medical radiology. [NIH] Radiotherapy: The use of ionizing radiation to treat malignant neoplasms and other benign conditions. The most common forms of ionizing radiation used as therapy are x-rays, gamma rays, and electrons. A special form of radiotherapy, targeted radiotherapy, links a cytotoxic radionuclide to a molecule that targets the tumor. When this molecule is an antibody or other immunologic molecule, the technique is called radioimmunotherapy. [NIH] Ramus: Most commonly used for branches of nerves, but applied also to other structures. [NIH]

Randomized: Describes an experiment or clinical trial in which animal or human subjects are assigned by chance to separate groups that compare different treatments. [NIH] Rape: Unlawful sexual intercourse without consent of the victim. [NIH] 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, Nicotinic: One of the two major classes of cholinergic receptors. Nicotinic receptors were originally distinguished by their preference for nicotine over muscarine. They are generally divided into muscle-type and neuronal-type (previously ganglionic) based on pharmacology, molecular biology, and biophysical properties of the channels. [NIH] Recombinant: A cell or an individual with a new combination of genes not found together in either parent; usually applied to linked genes. [EU] Recombination: The formation of new combinations of genes as a result of segregation in crosses between genetically different parents; also the rearrangement of linked genes due to crossing-over. [NIH] Reconstitution: 1. A type of regeneration in which a new organ forms by the rearrangement of tissues rather than from new formation at an injured surface. 2. The restoration to original form of a substance previously altered for preservation and storage, as the restoration to a liquid state of blood serum or plasma that has been dried and stored. [EU] Rectum: The last 8 to 10 inches of the large intestine. [NIH] Recurrence: The return of a sign, symptom, or disease after a remission. [NIH] Red blood cells: RBCs. Cells that carry oxygen to all parts of the body. Also called erythrocytes. [NIH] 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] Reflex: An involuntary movement or exercise of function in a part, excited in response to a stimulus applied to the periphery and transmitted to the brain or spinal cord. [NIH] Reflux: The term used when liquid backs up into the esophagus from the stomach. [NIH] Refraction: A test to determine the best eyeglasses or contact lenses to correct a refractive error (myopia, hyperopia, or astigmatism). [NIH] Refractive Errors: Deviations from the average or standard indices of refraction of the eye through its dioptric or refractive apparatus. [NIH]


Refractory: Not readily yielding to treatment. [EU] Regeneration: The natural renewal of a structure, as of a lost tissue or part. [EU] Regimen: A treatment plan that specifies the dosage, the schedule, and the duration of treatment. [NIH] 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] Relapse: The return of signs and symptoms of cancer after a period of improvement. [NIH] Reliability: Used technically, in a statistical sense, of consistency of a test with itself, i. e. the extent to which we can assume that it will yield the same result if repeated a second time. [NIH]

Remission: A decrease in or disappearance of signs and symptoms of cancer. In partial remission, some, but not all, signs and symptoms of cancer have disappeared. In complete remission, all signs and symptoms of cancer have disappeared, although there still may be cancer in the body. [NIH] Renal cell cancer: Cancer that develops in the lining of the renal tubules, which filter the blood and produce urine. [NIH] Renal failure: Progressive renal insufficiency and uremia, due to irreversible and progressive renal glomerular tubular or interstitial disease. [NIH] Reproduction Techniques: Methods pertaining to the generation of new individuals. [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] Respirator: A mechanical device that helps a patient breathe; a mechanical ventilator. [NIH] Respiratory failure: Inability of the lungs to conduct gas exchange. [NIH] Respiratory Muscles: These include the muscles of the diaphragm and the intercostal muscles. [NIH] Respiratory Paralysis: Complete or severe weakness of the muscles of respiration. This condition may be associated with motor neuron diseases; peripheral nerve disorders; neuromuscular junction diseases; spinal cord diseases; injury to the phrenic nerve; and other disorders. [NIH] Respiratory System: The tubular and cavernous organs and structures, by means of which pulmonary ventilation and gas exchange between ambient air and the blood are brought about. [NIH] Restoration: Broad term applied to any inlay, crown, bridge or complete denture which restores or replaces loss of teeth or oral tissues. [NIH] Retina: The ten-layered nervous tissue membrane of the eye. It is continuous with the optic nerve and receives images of external objects and transmits visual impulses to the brain. Its outer surface is in contact with the choroid and the inner surface with the vitreous body. The outer-most layer is pigmented, whereas the inner nine layers are transparent. [NIH] 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]

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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] Ribavirin: 1-beta-D-Ribofuranosyl-1H-1,2,4-triazole-3-carboxamide. A nucleoside antimetabolite antiviral agent that blocks nucleic acid synthesis and is used against both RNA and DNA viruses. [NIH] Ribose: A pentose active in biological systems usually in its D-form. [NIH] Ricin: A protein phytotoxin from the seeds of Ricinus communis, the castor oil plant. It agglutinates cells, is proteolytic, and causes lethal inflammation and hemorrhage if taken internally. [NIH] Rickets: A condition caused by deficiency of vitamin D, especially in infancy and childhood, with disturbance of normal ossification. The disease is marked by bending and distortion of the bones under muscular action, by the formation of nodular enlargements on the ends and sides of the bones, by delayed closure of the fontanelles, pain in the muscles, and sweating of the head. Vitamin D and sunlight together with an adequate diet are curative, provided that the parathyroid glands are functioning properly. [EU] Rickettsiae: One of a group of obligate intracellular parasitic microorganisms, once regarded as intermediate in their properties between bacteria and viruses but now classified as bacteria in the order Rickettsiales, which includes 17 genera and 3 families: Rickettsiace. [NIH]

Rigidity: Stiffness or inflexibility, chiefly that which is abnormal or morbid; rigor. [EU] Risk factor: A habit, trait, condition, or genetic alteration that increases a person's chance of developing a disease. [NIH] Rod: A reception for vision, located in the retina. [NIH] Ryanodine: Insecticidal alkaloid isolated from Ryania speciosa; proposed as a myocardial depressant. [NIH] Saline: A solution of salt and water. [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] Schizoid: Having qualities resembling those found in greater degree in schizophrenics; a person of schizoid personality. [NIH] Schizophrenia: A mental disorder characterized by a special type of disintegration of the personality. [NIH] Schizotypal Personality Disorder: A personality disorder in which there are oddities of thought (magical thinking, paranoid ideation, suspiciousness), perception (illusions, depersonalization), speech (digressive, vague, overelaborate), and behavior (inappropriate affect in social interactions, frequently social isolation) that are not severe enough to characterize schizophrenia. [NIH]


Sclera: The tough white outer coat of the eyeball, covering approximately the posterior fivesixths of its surface, and continuous anteriorly with the cornea and posteriorly with the external sheath of the optic nerve. [EU] Sclerae: A circular furrow between the sclerocorneal junction and the iris. [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] Sebaceous: Gland that secretes sebum. [NIH] Second Messenger Systems: Systems in which an intracellular signal is generated in response to an intercellular primary messenger such as a hormone or neurotransmitter. They are intermediate signals in cellular processes such as metabolism, secretion, contraction, phototransduction, and cell growth. Examples of second messenger systems are the adenyl cyclase-cyclic AMP system, the phosphatidylinositol diphosphate-inositol triphosphate system, and the cyclic GMP system. [NIH] 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] 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] Semicircular canal: Three long canals of the bony labyrinth of the ear, forming loops and opening into the vestibule by five openings. [NIH] Senile: Relating or belonging to old age; characteristic of old age; resulting from infirmity of old age. [NIH] Sensibility: The ability to receive, feel and appreciate sensations and impressions; the quality of being sensitive; the extend to which a method gives results that are free from false negatives. [NIH] Sensitization: 1. Administration of antigen to induce a primary immune response; priming; immunization. 2. Exposure to allergen that results in the development of hypersensitivity. 3. The coating of erythrocytes with antibody so that they are subject to lysis by complement in the presence of homologous antigen, the first stage of a complement fixation test. [EU] Sensory loss: A disease of the nerves whereby the myelin or insulating sheath of myelin on the nerves does not stay intact and the messages from the brain to the muscles through the nerves are not carried properly. [NIH] Sequence Homology: The degree of similarity between sequences. Studies of amino acid and nucleotide sequences provide useful information about the genetic relatedness of certain species. [NIH] 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]

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Serologic: Analysis of a person's serum, especially specific immune or lytic serums. [NIH] Serology: The study of serum, especially of antigen-antibody reactions in vitro. [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] Serum Albumin: A major plasma protein that serves in maintaining the plasma colloidal osmotic pressure and transporting large organic anions. [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] Signs and Symptoms: Clinical manifestations that can be either objective when observed by a physician, or subjective when perceived by the patient. [NIH] Skeletal: Having to do with the skeleton (boney part of the body). [NIH] Skeleton: The framework that supports the soft tissues of vertebrate animals and protects many of their internal organs. The skeletons of vertebrates are made of bone and/or cartilage. [NIH] Skull: The skeleton of the head including the bones of the face and the bones enclosing the brain. [NIH] Sleep apnea: A serious, potentially life-threatening breathing disorder characterized by repeated cessation of breathing due to either collapse of the upper airway during sleep or absence of respiratory effort. [NIH] Small intestine: The part of the digestive tract that is located between the stomach and the large intestine. [NIH] Smallpox: A generalized virus infection with a vesicular rash. [NIH] Smooth muscle: Muscle that performs automatic tasks, such as constricting blood vessels. [NIH]

Social Environment: The aggregate of social and cultural institutions, forms, patterns, and processes that influence the life of an individual or community. [NIH] Sodium: An element that is a member of the alkali group of metals. It has the atomic symbol Na, atomic number 11, and atomic weight 23. With a valence of 1, it has a strong affinity for oxygen and other nonmetallic elements. Sodium provides the chief cation of the extracellular body fluids. Its salts are the most widely used in medicine. (From Dorland, 27th ed) Physiologically the sodium ion plays a major role in blood pressure regulation, maintenance of fluid volume, and electrolyte balance. [NIH]


Soft tissue: Refers to muscle, fat, fibrous tissue, blood vessels, or other supporting tissue of the body. [NIH] Solitary Nucleus: Gray matter located in the dorsomedial part of the medulla oblongata associated with the solitary tract. The solitary nucleus receives inputs from most organ systems including the terminations of the facial, glossopharyngeal, and vagus nerves. It is a major coordinator of autonomic nervous system regulation of cardiovascular, respiratory, gustatory, gastrointestinal, and chemoreceptive aspects of homeostasis. The solitary nucleus is also notable for the large number of neurotransmitters which are found therein. [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] Somatosensory Disorders: Disorders of sensory information received from superficial and deep regions of the body. The somatosensory system conveys neural impulses which pertain to proprioception, tactile sensation, thermal sensation, pressure sensation, and pain. Peripheral nervous system diseases; spinal cord diseases; and brain diseases may be associated with impaired or abnormal somatic sensation. [NIH] Sound wave: An alteration of properties of an elastic medium, such as pressure, particle displacement, or density, that propagates through the medium, or a superposition of such alterations. [NIH] Spasm: An involuntary contraction of a muscle or group of muscles. Spasms may involve skeletal muscle or smooth muscle. [NIH] Spasmodic: Of the nature of a spasm. [EU] Spatial disorientation: Loss of orientation in space where person does not know which way is up. [NIH] Specialist: In medicine, one who concentrates on 1 special branch of medical science. [NIH] Species: A taxonomic category subordinate to a genus (or subgenus) and superior to a subspecies or variety, composed of individuals possessing common characters distinguishing them from other categories of individuals of the same taxonomic level. In taxonomic nomenclature, species are designated by the genus name followed by a Latin or Latinized adjective or noun. [EU] Specificity: Degree of selectivity shown by an antibody with respect to the number and types of antigens with which the antibody combines, as well as with respect to the rates and the extents of these reactions. [NIH] Spectrin: A high molecular weight (220-250 kDa) water-soluble protein which can be extracted from erythrocyte ghosts in low ionic strength buffers. The protein contains no lipids or carbohydrates, is the predominant species of peripheral erythrocyte membrane proteins, and exists as a fibrous coating on the inner, cytoplasmic surface of the membrane. [NIH]

Spectrum: A charted band of wavelengths of electromagnetic vibrations obtained by refraction and diffraction. By extension, a measurable range of activity, such as the range of bacteria affected by an antibiotic (antibacterial s.) or the complete range of manifestations of a disease. [EU] Sperm: The fecundating fluid of the male. [NIH] Sphincter: A ringlike band of muscle fibres that constricts a passage or closes a natural

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orifice; called also musculus sphincter. [EU] Spike: The activation of synapses causes changes in the permeability of the dendritic membrane leading to changes in the membrane potential. This difference of the potential travels along the axon of the neuron and is called spike. [NIH] Spina bifida: A defect in development of the vertebral column in which there is a central deficiency of the vertebral lamina. [NIH] Spinal cord: The main trunk or bundle of nerves running down the spine through holes in the spinal bone (the vertebrae) from the brain to the level of the lower back. [NIH] Spinal Cord Diseases: Pathologic conditions which feature spinal cord damage or dysfunction, including disorders involving the meninges and perimeningeal spaces surrounding the spinal cord. Traumatic injuries, vascular diseases, infections, and inflammatory/autoimmune processes may affect the spinal cord. [NIH] Spinal Injuries: Injuries involving the vertebral column. [NIH] Spirochete: Lyme disease. [NIH] Spleen: An organ that is part of the lymphatic system. The spleen produces lymphocytes, filters the blood, stores blood cells, and destroys old blood cells. It is located on the left side of the abdomen near the stomach. [NIH] Spontaneous Abortion: The non-induced birth of an embryo or of fetus prior to the stage of viability at about 20 weeks of gestation. [NIH] Sporadic: Neither endemic nor epidemic; occurring occasionally in a random or isolated manner. [EU] Stabilization: The creation of a stable state. [EU] Standard therapy: A currently accepted and widely used treatment for a certain type of cancer, based on the results of past research. [NIH] Standardize: To compare with or conform to a standard; to establish standards. [EU] Stapedius: The stapedius muscle arises from the wall of the middle ear and is inserted into the neck of the stapes. Its action is to pull the head of the stapes backward. [NIH] Stapes: One of the three ossicles of the middle ear. It transmits sound vibrations from the incus to the internal ear. [NIH] Steel: A tough, malleable, iron-based alloy containing up to, but no more than, two percent carbon and often other metals. It is used in medicine and dentistry in implants and instrumentation. [NIH] Stem cell transplantation: A method of replacing immature blood-forming cells that were destroyed by cancer treatment. The stem cells are given to the person after treatment to help the bone marrow recover and continue producing healthy blood cells. [NIH] Stem Cells: Relatively undifferentiated cells of the same lineage (family type) that retain the ability to divide and cycle throughout postnatal life to provide cells that can become specialized and take the place of those that die or are lost. [NIH] Sterility: 1. The inability to produce offspring, i.e., the inability to conceive (female s.) or to induce conception (male s.). 2. The state of being aseptic, or free from microorganisms. [EU] Steroid: A group name for lipids that contain a hydrogenated cyclopentanoperhydrophenanthrene ring system. Some of the substances included in this group are progesterone, adrenocortical hormones, the gonadal hormones, cardiac aglycones, bile acids, sterols (such as cholesterol), toad poisons, saponins, and some of the carcinogenic hydrocarbons. [EU]


Stillbirth: The birth of a dead fetus or baby. [NIH] 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] Strabismus: Deviation of the eye which the patient cannot overcome. The visual axes assume a position relative to each other different from that required by the physiological conditions. The various forms of strabismus are spoken of as tropias, their direction being indicated by the appropriate prefix, as cyclo tropia, esotropia, exotropia, hypertropia, and hypotropia. Called also cast, heterotropia, manifest deviation, and squint. [EU] Stress: Forcibly exerted influence; pressure. Any condition or situation that causes strain or tension. Stress may be either physical or psychologic, or both. [NIH] Stricture: The abnormal narrowing of a body opening. Also called stenosis. [NIH] Stroke: Sudden loss of function of part of the brain because of loss of blood flow. Stroke may be caused by a clot (thrombosis) or rupture (hemorrhage) of a blood vessel to the brain. [NIH] Stromal: Large, veil-like cell in the bone marrow. [NIH] Stromal Cells: Connective tissue cells of an organ found in the loose connective tissue. These are most often associated with the uterine mucosa and the ovary as well as the hematopoietic system and elsewhere. [NIH] Strychnine: An alkaloid found in the seeds of nux vomica. It is a competitive antagonist at glycine receptors and thus a convulsant. It has been used as an analeptic, in the treatment of nonketotic hyperglycinemia and sleep apnea, and as a rat poison. [NIH] Subacute: Somewhat acute; between acute and chronic. [EU] Subarachnoid: Situated or occurring between the arachnoid and the pia mater. [EU] Subclinical: Without clinical manifestations; said of the early stage(s) of an infection or other disease or abnormality before symptoms and signs become apparent or detectable by clinical examination or laboratory tests, or of a very mild form of an infection or other disease or abnormality. [EU] 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] Sudden death: Cardiac arrest caused by an irregular heartbeat. The term "death" is somewhat misleading, because some patients survive. [NIH] Supplementation: Adding nutrients to the diet. [NIH] Support group: A group of people with similar disease who meet to discuss how better to cope with their cancer and treatment. [NIH] Suppression: A conscious exclusion of disapproved desire contrary with repression, in which the process of exclusion is not conscious. [NIH]

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Sympathetic Nervous System: The thoracolumbar division of the autonomic nervous system. Sympathetic preganglionic fibers originate in neurons of the intermediolateral column of the spinal cord and project to the paravertebral and prevertebral ganglia, which in turn project to target organs. The sympathetic nervous system mediates the body's response to stressful situations, i.e., the fight or flight reactions. It often acts reciprocally to the parasympathetic system. [NIH] Sympathomimetic: 1. Mimicking the effects of impulses conveyed by adrenergic postganglionic fibres of the sympathetic nervous system. 2. An agent that produces effects similar to those of impulses conveyed by adrenergic postganglionic fibres of the sympathetic nervous system. Called also adrenergic. [EU] Symptomatic: Having to do with symptoms, which are signs of a condition or disease. [NIH] Synapses: Specialized junctions at which a neuron communicates with a target cell. At classical synapses, a neuron's presynaptic terminal releases a chemical transmitter stored in synaptic vesicles which diffuses across a narrow synaptic cleft and activates receptors on the postsynaptic membrane of the target cell. The target may be a dendrite, cell body, or axon of another neuron, or a specialized region of a muscle or secretory cell. Neurons may also communicate through direct electrical connections which are sometimes called electrical synapses; these are not included here but rather in gap junctions. [NIH] Synapsis: The pairing between homologous chromosomes of maternal and paternal origin during the prophase of meiosis, leading to the formation of gametes. [NIH] Synaptic: Pertaining to or affecting a synapse (= site of functional apposition between neurons, at which an impulse is transmitted from one neuron to another by electrical or chemical means); pertaining to synapsis (= pairing off in point-for-point association of homologous chromosomes from the male and female pronuclei during the early prophase of meiosis). [EU] Synaptic Transmission: The communication from a neuron to a target (neuron, muscle, or secretory cell) across a synapse. In chemical synaptic transmission, the presynaptic neuron releases a neurotransmitter that diffuses across the synaptic cleft and binds to specific synaptic receptors. These activated receptors modulate ion channels and/or secondmessenger systems to influence the postsynaptic cell. Electrical transmission is less common in the nervous system, and, as in other tissues, is mediated by gap junctions. [NIH] Synaptic Vesicles: Membrane-bound compartments which contain transmitter molecules. Synaptic vesicles are concentrated at presynaptic terminals. They actively sequester transmitter molecules from the cytoplasm. In at least some synapses, transmitter release occurs by fusion of these vesicles with the presynaptic membrane, followed by exocytosis of their contents. [NIH] Syncope: A temporary suspension of consciousness due to generalized cerebral schemia, a faint or swoon. [EU] Synergistic: Acting together; enhancing the effect of another force or agent. [EU] Syphilis: A contagious venereal disease caused by the spirochete Treponema pallidum. [NIH]

Syringomyelia: The presence in the spinal cord of elongated central fluid containing cavities surrounded by gliosis. [NIH] Systemic: Affecting the entire body. [NIH] Systemic lupus erythematosus: SLE. A chronic inflammatory connective tissue disease marked by skin rashes, joint pain and swelling, inflammation of the kidneys, inflammation of the fibrous tissue surrounding the heart (i.e., the pericardium), as well as other problems. Not all affected individuals display all of these problems. May be referred to as lupus. [NIH]


Tacrolimus: A macrolide isolated from the culture broth of a strain of Streptomyces tsukubaensis that has strong immunosuppressive activity in vivo and prevents the activation of T-lymphocytes in response to antigenic or mitogenic stimulation in vitro. [NIH] Temporal: One of the two irregular bones forming part of the lateral surfaces and base of the skull, and containing the organs of hearing. [NIH] Testicular: Pertaining to a testis. [EU] Testis: Either of the paired male reproductive glands that produce the male germ cells and the male hormones. [NIH] 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] Thoracic: Having to do with the chest. [NIH] Thoracoscopy: Endoscopic examination, therapy or surgery of the pleural cavity. [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] Thrombin: An enzyme formed from prothrombin that converts fibrinogen to fibrin. (Dorland, 27th ed) EC 3.4.21.5. [NIH] Thrombocytopenia: A decrease in the number of blood platelets. [NIH] Thrombomodulin: A cell surface glycoprotein of endothelial cells that binds thrombin and serves as a cofactor in the activation of protein C and its regulation of blood coagulation. [NIH]

Thrombosis: The formation or presence of a blood clot inside a blood vessel. [NIH] Thrombus: An aggregation of blood factors, primarily platelets and fibrin with entrapment of cellular elements, frequently causing vascular obstruction at the point of its formation. Some authorities thus differentiate thrombus formation from simple coagulation or clot formation. [EU] Thymoma: A tumor of the thymus, an organ that is part of the lymphatic system and is located in the chest, behind the breastbone. [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] Thymus Gland: A single, unpaired primary lymphoid organ situated in the mediastinum, extending superiorly into the neck to the lower edge of the thyroid gland and inferiorly to the fourth costal cartilage. It is necessary for normal development of immunologic function early in life. By puberty, it begins to involute and much of the tissue is replaced by fat. [NIH] Thyroid: A gland located near the windpipe (trachea) that produces thyroid hormone, which helps regulate growth and metabolism. [NIH] Thyroid Gland: A highly vascular endocrine gland consisting of two lobes, one on either side of the trachea, joined by a narrow isthmus; it produces the thyroid hormones which are

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concerned in regulating the metabolic rate of the body. [NIH] Thyroid Hormones: Hormones secreted by the thyroid gland. [NIH] Thyroiditis: Inflammation of the thyroid gland. [NIH] Thyrotropin: A peptide hormone secreted by the anterior pituitary. It promotes the growth of the thyroid gland and stimulates the synthesis of thyroid hormones and the release of thyroxine by the thyroid gland. [NIH] Thyroxine: An amino acid of the thyroid gland which exerts a stimulating effect on thyroid metabolism. [NIH] Tin: A trace element that is required in bone formation. It has the atomic symbol Sn, atomic number 50, and atomic weight 118.71. [NIH] 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] Tobramycin: An aminoglycoside, broad-spectrum antibiotic produced by Streptomyces tenebrarius. It is effective against gram-negative bacteria, especially the Pseudomonas species. It is a 10% component of the antibiotic complex, nebramycin, produced by the same species. [NIH] Tolerance: 1. The ability to endure unusually large doses of a drug or toxin. 2. Acquired drug tolerance; a decreasing response to repeated constant doses of a drug or the need for increasing doses to maintain a constant response. [EU] Tonic: 1. Producing and restoring the normal tone. 2. Characterized by continuous tension. 3. A term formerly used for a class of medicinal preparations believed to have the power of restoring normal tone to tissue. [EU] Tonicity: The normal state of muscular tension. [NIH] Topical: On the surface of the body. [NIH] Torticollis: Wryneck; a contracted state of the cervical muscles, producing twisting of the neck and an unnatural position of the head. [EU] Toxic: Having to do with poison or something harmful to the body. Toxic substances usually cause unwanted side effects. [NIH] Toxicity: The quality of being poisonous, especially the degree of virulence of a toxic microbe or of a poison. [EU] Toxicology: The science concerned with the detection, chemical composition, and pharmacologic action of toxic substances or poisons and the treatment and prevention of toxic manifestations. [NIH] Toxins: Specific, characterizable, poisonous chemicals, often proteins, with specific biological properties, including immunogenicity, produced by microbes, higher plants, or animals. [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]


Transfection: The uptake of naked or purified DNA into cells, usually eukaryotic. It is analogous to bacterial transformation. [NIH] Transfer Factor: Factor derived from leukocyte lysates of immune donors which can transfer both local and systemic cellular immunity to nonimmune recipients. [NIH] Transferases: Transferases are enzymes transferring a group, for example, the methyl group or a glycosyl group, from one compound (generally regarded as donor) to another compound (generally regarded as acceptor). The classification is based on the scheme "donor:acceptor group transferase". (Enzyme Nomenclature, 1992) EC 2. [NIH] Transforming Growth Factor alpha: Factor isolated in a variety of tissues including epithelium, and maternal decidua. It is closely related to epidermal growth factor and binds to the EGF receptor. TGF-alpha acts synergistically with TGF-beta in inducing phenotypic transformation, but its physiological role is unknown. [NIH] 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]

Transforming Growth Factors: Hormonally active polypeptides that can induce the transformed phenotype when added to normal, non-transformed cells. They have been found in culture fluids from retrovirally transformed cells and in tumor-derived cells as well as in non-neoplastic sources. Their transforming activities are due to the simultaneous action of two otherwise unrelated factors, transforming growth factor alpha and transforming growth factor beta. [NIH] Translational: The cleavage of signal sequence that directs the passage of the protein through a cell or organelle membrane. [NIH] Transmitter: A chemical substance which effects the passage of nerve impulses from one cell to the other at the synapse. [NIH] Transplantation: Transference of a tissue or organ, alive or dead, within an individual, between individuals of the same species, or between individuals of different species. [NIH] Trauma: Any injury, wound, or shock, must frequently physical or structural shock, producing a disturbance. [NIH] Tremor: Cyclical movement of a body part that can represent either a physiologic process or a manifestation of disease. Intention or action tremor, a common manifestation of cerebellar diseases, is aggravated by movement. In contrast, resting tremor is maximal when there is no attempt at voluntary movement, and occurs as a relatively frequent manifestation of Parkinson disease. [NIH] Tricyclic: Containing three fused rings or closed chains in the molecular structure. [EU] Trigeminal: Cranial nerve V. It is sensory for the eyeball, the conjunctiva, the eyebrow, the skin of face and scalp, the teeth, the mucous membranes in the mouth and nose, and is motor to the muscles of mastication. [NIH] Trochlear Nerve: The 4th cranial nerve. The trochlear nerve carries the motor innervation of the superior oblique muscles of the eye. [NIH] Trochlear Nerve Diseases: Diseases of the fourth cranial (trochlear) nerve or its nucleus in the midbrain. The nerve crosses as it exits the midbrain dorsally and may be injured along

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its course through the intracranial space, cavernous sinus, superior orbital fissure, or orbit. Clinical manifestations include weakness of the superior oblique muscle which causes vertical diplopia that is maximal when the affected eye is adducted and directed inferiorly. Head tilt may be seen as a compensatory mechanism for diplopia and rotation of the visual axis. Common etiologies include craniocerebral trauma and infratentorial neoplasms. [NIH] Tropomyosin: A protein found in the thin filaments of muscle fibers. It inhibits contraction of the muscle unless its position is modified by troponin. [NIH] Troponin: One of the minor protein components of skeletal muscle. Its function is to serve as the calcium-binding component in the troponin-tropomyosin B-actin-myosin complex by conferring calcium sensitivity to the cross-linked actin and myosin filaments. [NIH] 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] Tubocurarine: A neuromuscular blocker and active ingredient in curare; plant based alkaloid of Menispermaceae. [NIH] Tumor-derived: Taken from an individual's own tumor tissue; may be used in the development of a vaccine that enhances the body's ability to build an immune response to the tumor. [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] Tyrosine: A non-essential amino acid. In animals it is synthesized from phenylalanine. It is also the precursor of epinephrine, thyroid hormones, and melanin. [NIH] Unconscious: Experience which was once conscious, but was subsequently rejected, as the "personal unconscious". [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] 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] Uterus: The small, hollow, pear-shaped organ in a woman's pelvis. This is the organ in which a fetus develops. Also called the womb. [NIH] Uvea: The middle coat of the eyeball, consisting of the choroid in the back of the eye and the ciliary body and iris in the front of the eye. [NIH] Uveitis: An inflammation of part or all of the uvea, the middle (vascular) tunic of the eye, and commonly involving the other tunics (the sclera and cornea, and the retina). [EU] Vaccination: Administration of vaccines to stimulate the host's immune response. This includes any preparation intended for active immunological prophylaxis. [NIH] Vaccine: A substance or group of substances meant to cause the immune system to respond to a tumor or to microorganisms, such as bacteria or viruses. [NIH] Vaccinia: The cutaneous and occasional systemic reactions associated with vaccination


using smallpox (variola) vaccine. [NIH] Vaccinia Virus: The type species of Orthopoxvirus, related to cowpox virus, but whose true origin is unknown. It has been used as a live vaccine against smallpox. It is also used as a vector for inserting foreign DNA into animals. Rabbitpox virus is a subspecies of vaccinia virus. [NIH] Vacuoles: Any spaces or cavities within a cell. They may function in digestion, storage, secretion, or excretion. [NIH] Vagal: Pertaining to the vagus nerve. [EU] Vagina: The muscular canal extending from the uterus to the exterior of the body. Also called the birth canal. [NIH] Vaginitis: Inflammation of the vagina characterized by pain and a purulent discharge. [NIH] Vagus Nerve: The 10th cranial nerve. The vagus is a mixed nerve which contains somatic afferents (from skin in back of the ear and the external auditory meatus), visceral afferents (from the pharynx, larynx, thorax, and abdomen), parasympathetic efferents (to the thorax and abdomen), and efferents to striated muscle (of the larynx and pharynx). [NIH] Valine: A branched-chain essential amino acid that has stimulant activity. It promotes muscle growth and tissue repair. It is a precursor in the penicillin biosynthetic pathway. [NIH]

Variola: A generalized virus infection with a vesicular rash. [NIH] Vascular: Pertaining to blood vessels or indicative of a copious blood supply. [EU] Vasculitis: Inflammation of a blood vessel. [NIH] Vasoactive: Exerting an effect upon the calibre of blood vessels. [EU] Vasoactive Intestinal Peptide: A highly basic, single-chain polypeptide isolated from the intestinal mucosa. It has a wide range of biological actions affecting the cardiovascular, gastrointestinal, and respiratory systems. It is also found in several parts of the central and peripheral nervous systems and is a neurotransmitter. [NIH] Vasodilator: An agent that widens blood vessels. [NIH] VE: The total volume of gas either inspired or expired in one minute. [NIH] Vector: Plasmid or other self-replicating DNA molecule that transfers DNA between cells in nature or in recombinant DNA technology. [NIH] Vein: Vessel-carrying blood from various parts of the body to the heart. [NIH] Venereal: Pertaining or related to or transmitted by sexual contact. [EU] Venous: Of or pertaining to the veins. [EU] Venous blood: Blood that has given up its oxygen to the tissues and carries carbon dioxide back for gas exchange. [NIH] Ventilation: 1. In respiratory physiology, the process of exchange of air between the lungs and the ambient air. Pulmonary ventilation (usually measured in litres per minute) refers to the total exchange, whereas alveolar ventilation refers to the effective ventilation of the alveoli, in which gas exchange with the blood takes place. 2. In psychiatry, verbalization of one's emotional problems. [EU] Ventilator: A breathing machine that is used to treat respiratory failure by promoting ventilation; also called a respirator. [NIH] 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

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body through the aorta. [NIH] Ventricular: Pertaining to a ventricle. [EU] Verapamil: A calcium channel blocker that is a class IV anti-arrhythmia agent. [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] Vesicular: 1. Composed of or relating to small, saclike bodies. 2. Pertaining to or made up of vesicles on the skin. [EU] Vestibular: Pertaining to or toward a vestibule. In dental anatomy, used to refer to the tooth surface directed toward the vestibule of the mouth. [EU] Vestibule: A small, oval, bony chamber of the labyrinth. The vestibule contains the utricle and saccule, organs which are part of the balancing apparatus of the ear. [NIH] Vestibulocochlear Nerve: The 8th cranial nerve. The vestibulocochlear nerve has a cochlear part (cochlear nerve) which is concerned with hearing and a vestibular part (vestibular nerve) which mediates the sense of balance and head position. The fibers of the cochlear nerve originate from neurons of the spiral ganglion and project to the cochlear nuclei (cochlear nucleus). The fibers of the vestibular nerve arise from neurons of Scarpa's ganglion and project to the vestibular nuclei. [NIH] Vestibulocochlear Nerve Diseases: Diseases of the vestibular and/or cochlear (acoustic) nerves, which join to form the vestibulocochlear nerve. Vestibular neuritis, cochlear neuritis, and acoustic neuromas are relatively common conditions that affect these nerves. Clinical manifestations vary with which nerve is primarily affected, and include hearing loss, vertigo, and tinnitus. [NIH] Veterinary Medicine: The medical science concerned with the prevention, diagnosis, and treatment of diseases in animals. [NIH] Villi: The tiny, fingerlike projections on the surface of the small intestine. Villi help absorb nutrients. [NIH] Villous: Of a surface, covered with villi. [NIH] Vinca Alkaloids: A class of alkaloids from the genus of apocyanaceous woody herbs including periwinkles. They are some of the most useful antineoplastic agents. [NIH] Vincristine: An anticancer drug that belongs to the family of plant drugs called vinca alkaloids. [NIH] Vinyl Chloride: A gas that has been used as an aerosol propellant and is the starting material for polyvinyl resins. Toxicity studies have shown various adverse effects, particularly the occurrence of liver neoplasms. [NIH] Viral: Pertaining to, caused by, or of the nature of virus. [EU] Virulence: The degree of pathogenicity within a group or species of microorganisms or viruses as indicated by case fatality rates and/or the ability of the organism to invade the tissues of the host. [NIH] Virus: Submicroscopic organism that causes infectious disease. In cancer therapy, some viruses may be made into vaccines that help the body build an immune response to, and kill, tumor cells. [NIH] Viscera: Any of the large interior organs in any one of the three great cavities of the body,


especially in the abdomen. [NIH] Visceral: , from viscus a viscus) pertaining to a viscus. [EU] Visceral Afferents: The sensory fibers innervating the viscera. [NIH] Visual Cortex: Area of the occipital lobe concerned with vision. [NIH] Vitiligo: A disorder consisting of areas of macular depigmentation, commonly on extensor aspects of extremities, on the face or neck, and in skin folds. Age of onset is often in young adulthood and the condition tends to progress gradually with lesions enlarging and extending until a quiescent state is reached. [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] Vocal cord: The vocal folds of the larynx. [NIH] Voice Disorders: Disorders of voice pitch, loudness, or quality. Dysphonia refers to impaired utterance of sounds by the vocal folds. [NIH] Vomica: The profuse and sudden expectoration of pus and putrescent matter. An abnormal cavity in an organ especially in the lung, caused by suppuration and the breaking down of tissue. [NIH] Vulgaris: An affection of the skin, especially of the face, the back and the chest, due to chronic inflammation of the sebaceous glands and the hair follicles. [NIH] Wakefulness: A state in which there is an enhanced potential for sensitivity and an efficient responsiveness to external stimuli. [NIH] White blood cell: A type of cell in the immune system that helps the body fight infection and disease. White blood cells include lymphocytes, granulocytes, macrophages, and others. [NIH]

Windpipe: A rigid tube, 10 cm long, extending from the cricoid cartilage to the upper border of the fifth thoracic vertebra. [NIH] Withdrawal: 1. A pathological retreat from interpersonal contact and social involvement, as may occur in schizophrenia, depression, or schizoid avoidant and schizotypal personality disorders. 2. (DSM III-R) A substance-specific organic brain syndrome that follows the cessation of use or reduction in intake of a psychoactive substance that had been regularly used to induce a state of intoxication. [EU] Wound Healing: Restoration of integrity to traumatized tissue. [NIH] Xenograft: The cells of one species transplanted to another species. [NIH] X-ray: High-energy radiation used in low doses to diagnose diseases and in high doses to 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]

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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]

249

INDEX 3 3-dimensional, 15, 173, 229 A Abdomen, 173, 182, 210, 212, 237, 238, 244, 246 Abdominal, 173, 183, 193, 223 Abducens, 173, 193 Abducens Nerve, 173, 193 Abducens Nerve Diseases, 173, 193 Abductor, 38, 173 Aberrant, 19, 173 Acantholysis, 173, 224 Accommodation, 32, 173, 222 Acetylcholinesterase, 12, 13, 102, 109, 113, 173 Actin, 173, 217, 218, 243 Actinin, 173, 195 Action Potentials, 24, 173 Acute renal, 65, 173, 204 Adaptability, 174, 185 Adaptation, 174, 217, 227 Adenine, 174, 230 Adenosine, 5, 106, 174, 225 Adjuvant, 31, 174, 202 Adoptive Transfer, 28, 31, 174 Adrenal Cortex, 174, 190, 228 Adrenaline, 174 Adrenergic, 38, 174, 194, 197, 239 Adrenoreceptor, 80, 174 Adverse Effect, 32, 174, 235, 245 Aerosol, 174, 245 Afferent, 174, 190 Affinity, 16, 20, 31, 174, 175, 235 Agar, 174, 226 Agonist, 22, 109, 175, 194, 221 Agrin, 10, 175 Airway, 156, 175, 235 Albumin, 20, 21, 102, 103, 175, 226, 230, 235 Alexia, 175, 195 Algorithms, 175, 182 Alkaline, 175, 180, 183 Alkaloid, 104, 175, 179, 188, 216, 221, 233, 238, 243 Allergen, 175, 192, 234 Allogeneic, 14, 82, 107, 175, 203 Allogeneic bone marrow transplantation, 82, 175

Alopecia, 18, 175, 191 Alpha Particles, 175, 230 Alternative medicine, 87, 94, 134, 175, 189 Alternative Splicing, 175, 219 Alveolar Process, 175, 232 Ameliorated, 10, 176 Amino Acid Sequence, 105, 110, 176, 177, 198 Amino Acid Substitution, 110, 176 Amino Acids, 19, 176, 220, 222, 224, 227, 229, 234 Amphetamines, 176, 188 Amyloid, 101, 118, 176 Anaesthesia, 39, 45, 68, 74, 76, 82, 90, 176, 208 Analeptic, 176, 238 Analgesic, 176, 216, 222 Analog, 30, 33, 176 Analogous, 14, 176, 194, 227, 242 Anaphylatoxins, 176, 189 Anatomical, 176, 208, 217, 234 Androgens, 174, 176, 190 Anemia, 18, 103, 107, 176, 178, 225 Anesthesia, 35, 36, 47, 87, 89, 175, 177, 191, 220, 226 Aneurism, 101, 118, 177 Aneurysm, 101, 118, 177, 178, 201 Angiogenesis, 177, 214 Angiopathy, 101, 118, 177 Animal model, 8, 9, 15, 17, 27, 30, 102, 118, 134, 177 Anions, 175, 177, 210, 235 Anorexia, 107, 176, 177, 223 Anterior Cerebral Artery, 177, 185 Anthelmintic, 30, 177 Antiallergic, 177, 190 Antibacterial, 30, 177, 236 Antibiotic, 177, 183, 218, 224, 236, 241 Anticholinergic, 36, 102, 177, 226 Anticoagulant, 63, 177, 229 Antidote, 102, 178 Antiepileptic, 81, 178 Antifungal, 29, 178 Antigen-Antibody Complex, 178, 189 Antigen-presenting cell, 111, 178 Anti-inflammatory, 23, 127, 178, 190, 192, 202, 228 Anti-Inflammatory Agents, 23, 178, 190


Antimetabolite, 178, 233 Antineoplastic, 178, 190, 191, 245 Antiserum, 116, 178 Antiviral, 29, 178, 209, 224, 233 Anxiety, 122, 178 Aorta, 178, 245 Aortic Aneurysm, 101, 118, 178, 201 Apathy, 115, 178 Aphasia, 128, 178 Aplasia, 38, 178 Aplastic anemia, 107, 178 Apnea, 115, 178, 235, 238 Aponeurosis, 178, 201 Apoptosis, 17, 178 Apraxia, 128, 179 Arginine, 176, 179, 243 Aromatic, 106, 107, 179 Arrhythmia, 179, 245 Arterial, 179, 185, 206, 229 Arteries, 177, 178, 179, 182, 190, 211, 215 Articular, 179, 214 Articulation, 129, 179, 194 Arytenoid Cartilage, 128, 179 Aspiration, 51, 179 Assay, 14, 100, 103, 104, 179, 207, 230 Astringents, 179, 215 Ataxia, 125, 179, 185, 205, 240 Atrophy, 127, 168, 173, 179, 217, 219, 220 Atropine, 102, 179, 181 Attenuated, 17, 179 Auditory, 39, 179, 198, 204, 244 Autoantibodies, 7, 8, 15, 19, 22, 31, 36, 37, 47, 56, 57, 100, 101, 179 Autoantigens, 7, 179 Autoimmunity, 7, 10, 11, 15, 16, 18, 19, 28, 36, 37, 38, 40, 50, 55, 56, 110, 179 Autonomic, 8, 12, 15, 64, 125, 173, 179, 180, 181, 191, 201, 202, 219, 221, 225, 236, 239 Autonomic Nervous System, 8, 12, 180, 181, 219, 225, 236, 239 Autonomic Neuropathy, 15, 64, 180 Autoradiography, 9, 180 Avian, 105, 180 B Bacteria, 177, 178, 180, 201, 203, 213, 215, 233, 236, 241, 243 Bactericidal, 180, 198 Bacteriophage, 180, 226 Bacterium, 180, 204 Barium, 126, 180, 198 Barium swallow, 126, 180, 198

Basal Ganglia, 179, 180, 183, 187, 201, 217 Basal Ganglia Diseases, 179, 180, 187, 217 Base, 173, 174, 180, 192, 211, 227, 240 Basement Membrane, 180, 199, 211 Basophils, 180, 212 Belladonna, 179, 181 Benign, 135, 181, 183, 201, 204, 219, 231 Benzene, 101, 181 Beta-Galactosidase, 20, 181 Beta-pleated, 176, 181 Bifida, 125, 129, 181, 219, 237 Bile, 181, 201, 205, 212, 228, 237 Bile Acids, 181, 201, 237 Bile Ducts, 181, 228 Bilirubin, 175, 181 Binding Sites, 16, 22, 181 Bioassay, 104, 181 Biochemical, 54, 56, 88, 100, 101, 123, 156, 178, 181, 200, 203, 211, 235 Biochemical Phenomena, 181 Biological Phenomena, 29, 181 Biological response modifier, 181, 209 Biological therapy, 181, 204 Biopsy, 181, 224 Biosynthesis, 181, 222, 229, 234 Biotechnology, 16, 32, 34, 124, 134, 145, 181 Bipolar Disorder, 122, 182 Bladder, 39, 180, 182, 187, 208, 217, 219, 243 Blastocyst, 182, 189, 196, 226 Blasts, 16, 182 Blepharoptosis, 70, 72, 82, 182 Blister, 182, 224 Blood Cell Count, 182, 225 Blood Coagulation, 182, 183, 240 Blood Glucose, 182, 204, 209 Blood Platelets, 182, 235, 240 Blood pressure, 182, 201, 206, 216, 235 Blood-Brain Barrier, 113, 182, 214, 219, 226 Bone Marrow, 11, 14, 16, 82, 175, 178, 181, 182, 191, 203, 207, 213, 216, 226, 237, 238 Bone Marrow Transplantation, 14, 82, 175, 182 Bowel, 11, 67, 182, 193, 208, 210, 219 Bowel Movement, 182, 193 Brachytherapy, 182, 210, 230, 246 Brain Diseases, 182, 230, 236 Brain Neoplasms, 183, 205, 240 Brain Stem, 183, 193, 230 Branch, 165, 183, 195, 213, 220, 224, 236, 240

Index 251

Broad-spectrum, 183, 241 Buccal, 183, 213 Bulbar, 40, 67, 183, 230 Burns, 101, 118, 183 Burns, Electric, 183 Butyric Acid, 101, 183 Butyrylcholinesterase, 102, 109, 183 C Caesarean section, 68, 183 Calcitonin Gene-Related Peptide, 51, 183 Calcium, 7, 25, 71, 80, 183, 188, 214, 223, 243, 245 Calcium channel blocker, 183, 245 Calcium Channels, 7, 25, 183 Calculi, 183, 203 Candidiasis, 61, 184 Candidosis, 184 Carbohydrate, 105, 184, 190, 203, 227 Carbon Dioxide, 184, 200, 201, 226, 232, 244 Carcinogenic, 181, 184, 209, 222, 237 Carcinoma, 43, 60, 67, 184 Cardiac, 184, 196, 197, 218, 233, 237, 238 Cardiovascular, 180, 183, 184, 235, 236, 244 Cardiovascular System, 180, 184 Carrier Proteins, 184, 226, 230 Case report, 4, 49, 67, 74, 85, 184, 187 Case series, 184, 187 Castor Oil, 184, 233 Catabolism, 10, 184 Catecholamine, 184, 194 Cations, 184, 210 Caudal, 184, 206, 227 Celiac Disease, 18, 184 Cell Adhesion, 31, 185 Cell Adhesion Molecules, 31, 185 Cell Death, 17, 178, 185, 219 Cell Differentiation, 104, 105, 108, 185 Cell Division, 180, 185, 204, 214, 216, 226, 228 Cell membrane, 183, 184, 185, 201 Cell proliferation, 110, 185 Cell Size, 185, 200 Cell Survival, 185, 204 Cell Transplantation, 14, 185, 237 Cellulose, 185, 201, 226 Central Nervous System Infections, 185, 204, 205 Cerebellar, 179, 185, 231, 242 Cerebellar Diseases, 179, 185, 242 Cerebral Infarction, 65, 185, 205

Cerebral Palsy, 122, 125, 127, 128, 129, 186 Cerebrospinal, 186, 205 Cerebrospinal fluid, 186, 205 Cerebrovascular, 126, 129, 180, 186, 240 Cerebrum, 185, 186 Cervical, 128, 186, 225, 241 Cervical Plexus, 186, 225 Cervix, 186 Character, 186, 192, 203 Chelation, 90, 186 Chelation Therapy, 90, 186 Chemokines, 23, 186 Chemotactic Factors, 186, 189 Chemotherapy, 80, 89, 115, 186 Chest Pain, 135, 186 Cholesterol, 181, 186, 237 Choline, 12, 173, 186 Cholinergic, 6, 9, 15, 25, 47, 102, 104, 109, 113, 186, 187, 217, 221, 231 Cholinergic Agents, 102, 186 Cholinesterase Inhibitors, 109, 113, 114, 115, 187, 194 Chorea, 125, 129, 187 Choreatic Disorders, 187 Chromatin, 179, 187, 197 Chromosome, 187, 204, 212 Chronic Disease, 187, 212 Chymopapain, 187, 223 Ciliary, 13, 48, 187, 222, 235, 243 Ciliary Body, 187, 235, 243 Ciliary Neurotrophic Factor, 48, 187 Circulatory system, 187, 196, 210 CIS, 23, 26, 30, 187 Clamp, 12, 25, 187 Clinical study, 42, 125, 187 Clinical trial, 4, 11, 16, 31, 97, 98, 145, 187, 190, 191, 229, 231 Cloning, 82, 182, 187 Coal, 181, 188 Coca, 188 Cocaine, 48, 188 Cochlea, 188, 209 Cochlear, 188, 241, 245 Cochlear Diseases, 188, 241 Cofactor, 188, 229, 240 Cognition, 77, 127, 188 Colitis, 188, 208 Collagen, 180, 188, 199, 202, 214, 222 Collapse, 188, 235 Colloidal, 175, 188, 235 Communication Disorders, 98, 121, 128, 144, 188


Communis, 184, 188, 233 Complement, 12, 21, 30, 169, 176, 188, 189, 202, 214, 226, 234 Complement Activation, 30, 176, 189 Complementary and alternative medicine, 87, 94, 189 Complementary medicine, 87, 189 Complete remission, 70, 189, 232 Complete response, 189 Computational Biology, 145, 189 Conception, 189, 200, 228, 237 Conduction, 154, 169, 189, 220 Congenita, 132, 189 Congestion, 189, 197 Conjugated, 109, 110, 189 Conjunctiva, 189, 226, 242 Connective Tissue, 182, 188, 189, 200, 201, 202, 213, 232, 238, 239 Consciousness, 176, 190, 192, 194, 230, 239 Constitutional, 190, 218 Consumption, 103, 190, 232 Contraindications, ii, 190 Controlled study, 20, 21, 43, 190 Coordination, 190, 217 Cornea, 190, 234, 243 Corneal Ulcer, 101, 118, 190 Coronary, 115, 190, 215 Coronary Thrombosis, 190, 215 Cortex, 85, 174, 179, 183, 190, 193, 198, 199, 228, 231, 246 Cortical, 190, 198, 234, 240 Corticosteroid, 80, 85, 190, 228 Cortisol, 175, 190 Cortisone, 190, 192, 228 Cowpox, 190, 244 Cowpox Virus, 190, 244 Cranial, 111, 125, 128, 173, 190, 191, 202, 204, 206, 210, 219, 221, 222, 225, 230, 242, 244, 245 Cranial Nerves, 111, 125, 190, 191, 219 Craniocerebral Trauma, 173, 180, 191, 204, 205, 240, 241, 243 Creatine, 47, 89, 154, 191 Creatinine, 191 Cricoid Cartilage, 179, 191, 246 Critical Care, 35, 75, 191 Cues, 108, 191 Curare, 89, 92, 132, 191, 217, 243 Curative, 191, 221, 233, 240 Cutaneous, 83, 184, 186, 191, 213, 243 Cyclic, 29, 34, 112, 191, 225, 234

Cyclophosphamide, 75, 80, 85, 89, 134, 138, 191 Cyclosporine, 62, 138, 191 Cyst, 54, 191 Cysteine, 186, 187, 191, 196 Cytokine, 7, 8, 23, 31, 36, 58, 64, 67, 191, 209 Cytoplasm, 179, 180, 185, 191, 197, 216, 218, 239 Cytoskeletal Proteins, 191, 195 Cytotoxic, 30, 59, 107, 191, 209, 231 D Databases, Bibliographic, 145, 191 Deanol, 111, 192 Decidua, 192, 226, 242 Degenerative, 127, 135, 192, 202, 204, 217 Deletion, 10, 26, 179, 192 Delirium, 115, 192 Dementia, 104, 115, 122, 192, 220 Dendrites, 192, 220 Dendritic, 44, 192, 237 Density, 12, 14, 25, 112, 192, 200, 217, 222, 236 Dental Care, 130, 192 Depigmentation, 192, 246 Desensitization, 25, 192 Deuterium, 192, 205 Dexamethasone, 74, 192 Dexterity, 129, 192 Diabetes Mellitus, 18, 58, 93, 103, 107, 116, 192, 203, 204, 209 Diagnostic Imaging, 127, 192 Diagnostic procedure, 99, 135, 193 Diaphragm, 31, 186, 193, 225, 227, 232 Diarrhea, 107, 193 Digestion, 135, 181, 182, 193, 210, 212, 224, 238, 244 Digestive system, 98, 193 Digestive tract, 180, 193, 235 Dilatation, 177, 193 Dilation, 101, 118, 193, 205 Diploid, 193, 226 Diplopia, 112, 173, 193, 243 Direct, iii, 10, 11, 17, 22, 25, 31, 32, 56, 107, 137, 193, 194, 213, 231, 239 Discrimination, 108, 193 Disease Progression, 25, 193 Disease Susceptibility, 23, 193 Disinfectant, 193, 198 Dislocation, 128, 193 Disorientation, 192, 193, 194, 236 Dissection, 62, 193

Index 253

Dissociation, 174, 193 Distal, 46, 60, 194, 201, 225, 229 Dizziness, 129, 194, 245 Donepezil, 115, 194 Dopamine, 108, 188, 194 Dorsal, 194, 227 Dorsum, 194, 201 Drive, ii, vi, 40, 79, 108, 130, 194 Drug Approval, 122, 137, 194 Drug Design, 16, 22, 140, 194 Drug Interactions, 139, 194 Drug Tolerance, 194, 241 Duodenum, 181, 194, 223, 238 Dyes, 32, 176, 180, 194, 200 Dysarthria, 128, 129, 168, 194 Dyskinesia, 194 Dyslexia, 115, 195 Dysphagia, 61, 122, 126, 127, 135, 168, 195 Dysphonia, 122, 128, 168, 195, 246 Dystonia, 128, 195 Dystrophin, 14, 195 Dystrophy, 49, 101, 118, 124, 130, 154, 155, 156, 195 E Eating Disorders, 108, 195 Effector, 8, 28, 30, 31, 108, 173, 188, 195, 219, 220, 225 Effector cell, 28, 195, 219, 220 Efficacy, 5, 16, 29, 30, 194, 195 Elective, 68, 195 Electrolyte, 190, 192, 195, 216, 235 Electromyography, 12, 63, 154, 169, 195 Electrons, 180, 195, 210, 230, 231 Electrophysiological, 5, 9, 13, 27, 32, 43, 71, 110, 195 Elementary Particles, 195, 220, 229 Embryo, 182, 185, 195, 200, 208, 222, 227, 228, 237 Embryo Transfer, 195, 228 Emulsion, 180, 196, 200 Encephalitis, 52, 196 Encephalitis, Viral, 196 Encephalocele, 196, 219 Encephalomyelitis, 12, 28, 196 Encephalopathy, 126, 196 Endocarditis, 184, 196 Endocrine System, 196, 219 Endocytosis, 106, 196 Endopeptidases, 196, 229 Endoscope, 196, 211 Endoscopy, 126, 196 Endothelial cell, 182, 197, 240

Endotoxins, 189, 197 Enteropeptidase, 197, 243 Environmental Exposure, 116, 197 Environmental Health, 9, 144, 146, 197 Enzymatic, 183, 189, 197, 223 Eosinophils, 197, 212 Epidemiological, 116, 197 Epidermis, 173, 182, 197, 224, 230 Epidural, 39, 46, 197, 210 Epinephrine, 174, 194, 197, 221, 243 Epithelial, 52, 187, 190, 192, 197, 205, 211 Epithelial Cells, 52, 197, 205, 211 Epithelium, 20, 180, 197, 242 Epitope, 7, 16, 19, 21, 29, 33, 67, 71, 109, 110, 197 Epitope Mapping, 71, 197 Erythema, 34, 197 Erythrocytes, 105, 176, 182, 197, 231, 234 Esophageal, 37, 126, 135, 198, 201, 212 Esophageal Manometry, 126, 198 Esophageal Motility Disorders, 126, 198 Esophageal Spasms, 135, 198 Esophagram, 180, 198 Esophagus, 135, 180, 193, 198, 201, 212, 214, 222, 225, 231, 238 Esotropia, 173, 198, 238 Ethanol, 43, 198 Eukaryotic Cells, 191, 198, 208 Evoke, 198, 238 Evoked Potentials, 39, 198 Excitation, 25, 176, 198, 200 Excitatory, 6, 198 Exogenous, 198, 202, 225 Exon, 117, 175, 198 Exophthalmos, 53, 198 Exotoxin, 59, 198 Exotropia, 198, 238 Expiratory, 199, 225 Extensor, 199, 229, 246 External-beam radiation, 199, 210, 230, 246 Extracellular, 13, 15, 22, 27, 117, 176, 189, 190, 196, 199, 214, 235 Extracellular Matrix, 13, 189, 190, 199, 214 Extracellular Matrix Proteins, 199, 214 Extracellular Space, 199 Extraocular, 26, 30, 49, 199 Extrapyramidal, 194, 199 Extremity, 199, 223 Eye Movements, 26, 199, 230 F Facial, 3, 60, 111, 125, 129, 168, 199, 236


Facial Pain, 125, 199 Facial Paralysis, 125, 129, 199 Family Planning, 145, 199 Farnesyl, 30, 199 Fasciculation, 111, 199, 220 Fat, 177, 182, 183, 190, 199, 212, 217, 232, 236, 240 Fatigue, 25, 32, 50, 70, 87, 95, 116, 128, 158, 168, 200, 204, 215 Fatty acids, 175, 200 Fertilization in Vitro, 200, 228 Fetal Development, 200, 219 Fetus, 200, 207, 226, 237, 238, 243 Fibrosis, 26, 200, 234 Fixation, 200, 234 Flow Cytometry, 9, 200 Fluorescence, 14, 22, 200 Fluorescent Dyes, 200 Fold, 7, 15, 24, 38, 114, 128, 200 Frontal Lobe, 9, 115, 177, 185, 200 Fungi, 178, 200, 201, 215, 246 Fungus, 184, 201 G Galactosides, 105, 181, 201 Gallbladder, 173, 181, 193, 201 Ganglia, 15, 173, 179, 180, 183, 187, 201, 217, 219, 225, 239 Ganglion, 13, 201, 222, 245 Ganglionic Blockers, 201, 214 Gap Junctions, 201, 239 Gas, 184, 201, 205, 221, 232, 244, 245 Gas exchange, 201, 232, 244 Gasoline, 181, 201 Gastric, 198, 201, 224 Gastric Acid, 198, 201 Gastric Juices, 201, 224 Gastrin, 201, 205 Gastroesophageal Reflux, 135, 201 Gastrointestinal, 187, 197, 198, 202, 214, 235, 236, 238, 244 Gastrointestinal tract, 187, 198, 202, 214, 235 Gelatin, 202, 203, 240 Gene Expression, 25, 202 Gene Rearrangement, 72, 202 Gene Targeting, 10, 202 Genetic Engineering, 16, 182, 188, 202 Genetics, 6, 18, 52, 202 Genital, 180, 202 Genotype, 18, 26, 202, 225 Germ Cells, 202, 214, 222, 223, 236, 240 Germinal Center, 8, 21, 50, 72, 202

Gestation, 202, 226, 237 Gland, 44, 174, 190, 198, 202, 203, 206, 213, 223, 226, 234, 238, 240, 241 Gliosis, 202, 239 Glossopharyngeal Nerve, 199, 202 Glucocorticoid, 53, 192, 202, 228 Glucose, 182, 185, 192, 202, 203, 204, 206, 209, 233 Glucose Intolerance, 192, 203 Gluten, 184, 203 Glycerol, 183, 203 Glycine, 16, 203, 234, 238 Glycoprotein, 14, 203, 211, 240 Glycoside, 203, 233 Glycosylation, 105, 203 Goiter, 125, 203 Gonadal, 203, 237 Gonads, 203, 206 Gout, 126, 203 Governing Board, 203, 228 Gp120, 203, 224 Grade, 31, 203 Graft, 106, 107, 115, 203, 205, 207, 218, 229 Graft Rejection, 106, 107, 203, 207 Graft-versus-host disease, 106, 107, 203, 218, 229 Gram-negative, 203, 241 Growth factors, 13, 204 H Hair Cells, 9, 204 Hair follicles, 204, 246 Haploid, 204, 226 Haptens, 174, 204, 230 Headache, 129, 204, 205, 206 Headache Disorders, 204 Hearing Disorders, 188, 204 Heart failure, 101, 118, 204 Heartbeat, 204, 238 Hemoglobin, 176, 182, 198, 204 Hemolytic, 107, 204 Hemorrhage, 191, 204, 230, 233, 238 Hepatic, 175, 192, 204 Hepatitis, 45, 64, 65, 75, 204 Hepatocytes, 205 Heredity, 124, 202, 205 Heterodimer, 15, 205 Heterogeneity, 17, 18, 37, 54, 56, 61, 174, 205 Heterotropia, 205, 238 Histiocytosis, 61, 205 Hoarseness, 128, 168, 205 Homeostasis, 29, 205, 236

Index 255

Homologous, 105, 116, 202, 205, 234, 239 Hormonal, 179, 190, 205 Hormone, 103, 104, 174, 181, 190, 197, 201, 205, 209, 215, 223, 228, 233, 234, 240, 241, 242 Host, 16, 17, 28, 106, 107, 180, 184, 205, 207, 218, 243, 245 Humoral, 10, 19, 56, 57, 107, 203, 205 Humour, 205 Hybrid, 10, 205 Hydrocephalus, 129, 205, 210 Hydrogen, 114, 180, 184, 192, 199, 205, 216, 220, 229 Hydrolysis, 5, 173, 181, 206, 227, 229, 243 Hyperplasia, 8, 66, 206 Hypersensitivity, 175, 192, 206, 233, 234 Hypertension, 173, 204, 205, 206, 210, 214, 241 Hyperthyroidism, 62, 73, 90, 206 Hypertrophy, 206 Hyperuricemia, 203, 206 Hypoglossal Nerve, 71, 125, 206 Hypoglycaemia, 192, 206 Hypogonadism, 18, 206 Hypothalamus, 180, 183, 206, 226 Hypothermia, 32, 206 Hypothyroidism, 18, 206 Hypoxia, 32, 192, 206, 240 I Id, 19, 45, 86, 93, 157, 158, 164, 166, 206 Idiopathic, 107, 126, 206 Illusion, 206, 245 Immune Complex Diseases, 178, 206, 226 Immune Sera, 207 Immune Tolerance, 16, 207 Immunity, 20, 80, 105, 207, 209, 213, 242 Immunization, 7, 15, 31, 58, 109, 110, 174, 207, 234 Immunoassay, 103, 104, 207 Immunochemistry, 197, 207 Immunodeficiency, 60, 107, 207 Immunofluorescence, 10, 207 Immunogen, 7, 207 Immunogenic, 8, 15, 17, 19, 55, 57, 74, 117, 207, 230 Immunoglobulin, 20, 21, 48, 50, 53, 54, 55, 58, 59, 66, 70, 73, 82, 83, 89, 97, 100, 154, 177, 207, 216 Immunologic, 62, 174, 186, 206, 207, 231, 240 Immunosuppressive, 27, 44, 54, 65, 81, 100, 106, 107, 191, 202, 207, 240

Immunosuppressive therapy, 27, 44, 54, 100, 207 Immunotherapy, 17, 21, 54, 58, 174, 181, 192, 207 Immunotoxin, 85, 207 Impairment, 32, 53, 101, 125, 128, 129, 179, 192, 194, 195, 207, 215 Implant radiation, 208, 210, 230, 246 In situ, 9, 208 In Situ Hybridization, 9, 208 In vitro, 6, 15, 22, 23, 25, 26, 28, 44, 55, 58, 69, 71, 81, 91, 196, 208, 228, 235, 240 In vivo, 10, 14, 15, 21, 28, 31, 55, 88, 208, 240 Incision, 183, 208, 210 Incompetence, 201, 208 Incontinence, 205, 208 Incubated, 100, 208 Incubation, 100, 208, 212 Incubation period, 208, 212 Indicative, 122, 208, 224, 244 Induction, 8, 16, 22, 28, 30, 50, 58, 107, 176, 201, 208, 209 Infancy, 208, 233 Infarction, 65, 185, 190, 205, 208, 215 Infection, 65, 111, 180, 181, 184, 186, 187, 190, 192, 196, 207, 208, 212, 213, 220, 224, 233, 235, 238, 244, 246 Inflammation, 20, 101, 118, 175, 178, 187, 188, 196, 200, 204, 208, 218, 232, 233, 239, 241, 243, 244, 246 Inflammatory bowel disease, 67, 208 Ingestion, 103, 208, 227 Inhalation, 138, 174, 209, 227 Initiator, 209 Inner ear, 9, 188, 209 Innervation, 9, 206, 209, 222, 230, 242 Inotropic, 194, 209 Insight, 16, 19, 27, 209 Insulator, 209, 217 Insulin, 58, 103, 107, 209 Insulin-dependent diabetes mellitus, 58, 209 Intercostal, 84, 91, 209, 232 Interferon, 31, 36, 45, 58, 62, 64, 209 Interferon-alpha, 36, 45, 62, 209 Interleukin-1, 36, 58, 209 Interleukin-12, 36, 209 Interleukin-18, 58, 209 Interleukin-2, 46, 58, 59, 209 Interleukin-4, 66, 209 Intermittent, 111, 210


Internal radiation, 210, 230, 246 Interstitial, 182, 199, 210, 232, 246 Intestinal, 51, 184, 197, 210, 214, 244 Intestine, 181, 182, 194, 205, 210, 211, 231, 235, 243, 245 Intoxication, 126, 192, 210, 246 Intracellular, 10, 23, 208, 210, 215, 233, 234 Intracellular Membranes, 210, 215 Intracranial Hemorrhages, 205, 210, 240 Intracranial Hypertension, 173, 204, 205, 210, 241 Intracranial Pressure, 126, 210 Intraocular, 13, 210 Intravenous, 20, 21, 54, 55, 59, 70, 73, 75, 80, 82, 85, 90, 97, 134, 139, 154, 170, 210 Intrinsic, 13, 27, 127, 174, 180, 210, 211 Invasive, 207, 210 Involuntary, 180, 187, 210, 218, 231, 236 Ion Channels, 16, 22, 210, 220, 239 Ionizing, 175, 197, 210, 231 Ions, 106, 180, 183, 193, 195, 205, 210, 216 Irradiation, 107, 210, 246 Ischemia, 173, 179, 210 Ischemic stroke, 37, 211 J Joint, 14, 128, 179, 211, 213, 239 K Kb, 144, 211 Kinetic, 27, 210, 211, 225 L Labile, 188, 211 Labyrinth, 188, 209, 211, 228, 234, 245 Lacrimal, 211, 222 Lag, 116, 211 Laminin, 14, 180, 199, 211 Language Disorders, 188, 211 Large Intestine, 193, 210, 211, 231, 235 Laryngeal, 60, 82, 127, 128, 191, 211 Laryngeal Muscles, 128, 211 Laryngoscopy, 128, 211 Larynx, 128, 211, 218, 241, 244, 246 Latent, 211, 228 Lectin, 105, 211, 215 Lens, 189, 211 Lentivirus, 16, 211 Lesion, 12, 202, 212, 230 Lethal, 180, 212, 233 Lethargy, 205, 206, 212 Leucocyte, 212 Leukaemia, 41, 212 Leukemia, 69, 107, 212

Leukocytes, 101, 118, 180, 182, 186, 197, 209, 212, 216 Leukoencephalopathy, 12, 212 Library Services, 164, 212 Ligament, 179, 212 Ligands, 7, 15, 17, 57, 185, 212 Linkage, 18, 19, 61, 212 Lip, 128, 129, 212 Lipid, 186, 203, 209, 212, 217 Liver, 5, 173, 175, 181, 191, 193, 196, 201, 204, 205, 212, 228, 245 Liver Neoplasms, 212, 245 Lobe, 9, 115, 177, 185, 193, 200, 212, 221, 246 Localization, 9, 12, 18, 212 Localized, 61, 177, 195, 200, 208, 211, 212, 226, 234 Locomotion, 212, 226 Loop, 67, 212 Lower Esophageal Sphincter, 135, 198, 201, 212 Lucida, 211, 213 Luciferase, 23, 213 Lupus, 11, 18, 63, 65, 103, 107, 126, 206, 213, 239 Luxation, 193, 213 Lymph, 117, 186, 187, 197, 205, 213, 214 Lymph node, 117, 186, 213, 214 Lymphatic, 208, 213, 237, 240 Lymphatic system, 213, 237, 240 Lymphoblastic, 58, 213 Lymphocyte, 38, 84, 106, 178, 213, 214 Lymphocyte Subsets, 84, 213 Lymphoid, 23, 85, 177, 202, 212, 213, 240 Lymphokines, 108, 213 Lymphoma, 69, 83, 213 Lysine, 213, 243 M Macrolides, 29, 213 Macrophage, 28, 209, 213 Maintenance therapy, 21, 73, 213 Major Histocompatibility Complex, 82, 107, 111, 114, 209, 213 Malabsorption, 184, 214 Malformation, 41, 214 Malignancy, 198, 214 Malignant, 80, 89, 178, 183, 205, 214, 219, 231 Malnutrition, 103, 104, 175, 179, 214, 217 Mandible, 175, 214, 232 Mandibular Condyle, 53, 214 Mania, 115, 122, 214

Index 257

Manic, 182, 214 Manifest, 214, 238 Mastication, 43, 214, 242 Matrilysin, 102, 118, 214 Matrix metalloproteinase, 101, 117, 118, 214, 221 Mecamylamine, 108, 214 Mediastinum, 214, 240 Mediate, 6, 25, 30, 107, 185, 194, 214 Mediator, 5, 9, 209, 214, 235 MEDLINE, 145, 214 Medullary, 20, 85, 214 Meiosis, 214, 239 Membrane Proteins, 15, 24, 215, 236 Memory, 22, 29, 104, 115, 127, 177, 192, 202, 215 Meninges, 185, 191, 215, 237 Menstruation, 111, 192, 215 Mental Disorders, 98, 215, 229 Mental Fatigue, 70, 215 Mental Retardation, 188, 215 Mentors, 15, 215 Mercury, 126, 200, 215 Meta-Analysis, 18, 215 Metabolic disorder, 203, 215 Metastasis, 185, 214, 215 MI, 101, 117, 171, 215 Microbe, 215, 241 Microorganism, 188, 215, 224, 246 Microscopy, 14, 25, 180, 215 Mineralization, 216, 223 Mineralocorticoids, 174, 190, 216 Mitosis, 179, 216 Mobility, 13, 129, 216 Mobilization, 11, 216 Modeling, 194, 216 Modification, 102, 118, 126, 202, 216, 230 Molecular Structure, 216, 242 Monitor, 14, 103, 191, 216, 221 Monoclonal, 11, 27, 31, 56, 210, 216, 230, 246 Monoclonal antibodies, 27, 31, 216 Monocytes, 209, 212, 216 Mononuclear, 46, 59, 216 Monophosphate, 112, 216 Monotherapy, 59, 82, 216 Morphine, 82, 216, 218, 222 Morphology, 26, 44, 216 Motility, 26, 126, 198, 217, 235 Motion Sickness, 217, 218 Motor Activity, 217, 230 Motor Endplate, 27, 217

Motor nerve, 47, 199, 217, 221, 225 Movement Disorders, 39, 192, 217, 240 Mucinous, 201, 217 Mucosa, 184, 213, 217, 238, 244 Multidrug resistance, 106, 217 Muscarinic Agonists, 186, 217 Muscle Contraction, 22, 26, 32, 176, 195, 217 Muscle Fibers, 25, 175, 217, 218, 243 Muscle Hypertonia, 217, 220 Muscle relaxant, 217, 219 Muscle Relaxation, 176, 217, 218, 220 Muscular Atrophy, 127, 217 Muscular Diseases, 199, 217, 220, 230 Muscular Dystrophies, 10, 24, 127, 129, 195, 217 Musculoskeletal System, 127, 218 Mutagenesis, 22, 27, 218 Mutagens, 218 Mycophenolate mofetil, 65, 82, 84, 85, 218 Mydriatic, 193, 218 Myelin, 28, 217, 218, 234 Myocarditis, 116, 218 Myocardium, 215, 218 Myofibrils, 88, 195, 218 Myopathy, 71, 115, 126, 218 Myosin, 74, 90, 217, 218, 243 Myositis, 58, 65, 126, 218 Myotonia, 132, 218 N Narcotic, 216, 218 Nasalis, 43, 218 Natural killer cells, 209, 218 Nausea, 107, 218 NCI, 1, 98, 143, 187, 218 Nebramycin, 218, 241 Necrosis, 178, 185, 190, 208, 215, 218, 234 Need, 3, 27, 121, 125, 135, 140, 160, 214, 219, 241 Neonatal, 50, 55, 92, 219 Neoplasm, 122, 219, 243 Neoplastic, 199, 213, 219, 226, 242 Neostigmine, 111, 219 Nervous System Diseases, 219, 220, 225, 230, 236 Networks, 13, 29, 219 Neural, 12, 13, 25, 29, 47, 81, 125, 127, 174, 176, 183, 196, 201, 205, 219, 236 Neural tube defects, 125, 219 Neuregulins, 13, 219 Neuroanatomy, 129, 219


Neurodegenerative Diseases, 10, 113, 114, 180, 219 Neuroeffector Junction, 219, 221 Neuroendocrine, 12, 23, 219 Neurogenic, 121, 127, 128, 219 Neurologic, 12, 15, 115, 122, 125, 127, 128, 129, 135, 196, 205, 219 Neurologist, 15, 48, 100, 219 Neuromuscular Blockade, 74, 220 Neuromuscular Diseases, 14, 127, 220, 230 Neuromuscular Junction Diseases, 220, 232 Neuronal, 6, 15, 22, 24, 27, 183, 187, 220, 231 Neurons, 5, 13, 24, 113, 186, 188, 192, 198, 201, 217, 220, 221, 239, 245 Neuropathy, 15, 64, 65, 125, 180, 220, 225 Neuropeptide, 23, 183, 220 Neuropharmacology, 73, 81, 121, 220 Neurophysiology, 12, 43, 54, 63, 70, 71, 80, 90, 129, 220 Neurosyphilis, 220, 223 Neurotransmitters, 13, 22, 27, 216, 220, 236 Neutralization, 11, 21, 31, 220 Neutrons, 175, 210, 220, 230 Neutrophil, 102, 118, 221 Neutrophil Collagenase, 102, 118, 221 Niacin, 221, 243 Nicotine, 5, 22, 24, 27, 66, 108, 221, 231 Nicotinic Agonists, 28, 221 Nitrogen, 175, 176, 191, 199, 200, 221, 243 Nonverbal Communication, 188, 221 Norepinephrine, 174, 194, 221 Nuclear, 180, 195, 198, 201, 219, 221 Nuclei, 175, 177, 195, 199, 202, 216, 220, 221, 222, 229, 245 Nucleic acid, 208, 218, 221, 228, 230, 233 Nystagmus, 67, 221 O Occipital Lobe, 193, 221, 246 Ocular, 26, 30, 35, 37, 41, 44, 45, 49, 54, 57, 66, 67, 70, 71, 72, 81, 112, 198, 221, 222 Oculi, 72, 221 Oculomotor, 67, 193, 221, 222 Oculomotor Nerve, 193, 222 Odour, 179, 222 Odynophagia, 126, 222 Oligo, 55, 222 Oncogenic, 211, 222 Oocytes, 8, 27, 222 Opacity, 192, 222

Open Reading Frames, 212, 222 Ophthalmic, 70, 72, 74, 138, 222, 227 Ophthalmoplegia, 38, 82, 222 Opium, 216, 222 Oral Health, 125, 129, 222 Orbicularis, 72, 222 Orbit, 173, 222, 243 Orbital, 49, 173, 188, 222, 243 Orofacial, 199, 222 Osmotic, 175, 222, 235 Ossification, 222, 233 Osteogenesis, 129, 222 Osteogenesis Imperfecta, 129, 222 Osteomalacia, 129, 223 Osteoporosis, 64, 68, 83, 101, 118, 129, 223 Ovary, 203, 223, 227, 238 P Palate, 128, 129, 202, 223 Palliative, 223, 240 Palsies, 125, 223 Palsy, 115, 122, 125, 127, 128, 129, 186, 223 Pancreas, 173, 193, 209, 223, 243 Pancreatic, 103, 201, 223 Pancreatic Juice, 201, 223 Papain, 85, 223 Paralysis, 38, 125, 129, 168, 179, 182, 183, 191, 198, 199, 222, 223, 229, 230, 232 Paraneoplastic syndrome, 80, 223 Parathyroid, 223, 233 Parathyroid Glands, 223, 233 Paresis, 71, 199, 223 Paresthesias, 5, 223 Partial remission, 223, 232 Partnership Practice, 224, 228 Patch, 12, 224 Pathogen, 208, 224 Pathogenesis, 8, 11, 16, 18, 19, 20, 21, 30, 35, 73, 75, 123, 126, 224 Pathologic, 179, 181, 182, 184, 190, 206, 224, 229, 232, 237 Pathologic Processes, 179, 224 Pathophysiology, 13, 30, 124, 224 Patient Advocacy, 159, 224 Patient Education, 126, 156, 162, 164, 171, 224 Pemphigus, 11, 106, 173, 224 Penicillamine, 74, 81, 84, 224 Penicillin, 224, 244 Pepsin, 224 Peptic, 126, 135, 224 Peptide T, 70, 224 Perception, 127, 204, 224, 233

Index 259

Percutaneous, 43, 224 Perfusion, 206, 224 Pericardium, 224, 239 Periodontal disease, 101, 118, 224 Perioral, 5, 225 Peripheral blood, 46, 55, 59, 82, 110, 209, 225 Peripheral Nervous System, 194, 219, 220, 221, 223, 225, 230, 238, 244 Peripheral Nervous System Diseases, 220, 225, 230 Peripheral Neuropathy, 65, 225 Peripheral stem cells, 203, 225 Perivascular, 183, 225 Pernicious, 18, 103, 225 Pernicious anemia, 18, 103, 225 Pharmacokinetics, 194, 225 Pharmacologic, 32, 128, 177, 225, 241 Pharyngeal Muscles, 156, 225 Pharynx, 202, 218, 225, 244 Phenotype, 11, 19, 25, 26, 28, 225, 242 Phenyl, 109, 114, 225 Phonation, 127, 129, 225 Phosphodiesterase, 112, 225 Phosphorus, 183, 223, 225 Phosphorylation, 219, 225 Phrenic Nerve, 31, 225, 232 Physical Examination, 126, 225 Physiologic, 5, 9, 12, 175, 181, 193, 200, 215, 226, 231, 232, 242 Physiology, 10, 11, 19, 21, 30, 128, 135, 174, 195, 220, 226, 244 Physostigmine, 102, 109, 219, 226 Phytotoxin, 226, 233 Pilot study, 51, 226 Pipecuronium, 82, 226 Pitch, 226, 246 Pituitary Gland, 190, 226 Placenta, 105, 226, 228 Plana, 226, 235 Plants, 105, 175, 179, 181, 184, 186, 188, 202, 203, 211, 216, 221, 226, 227, 233, 241 Plaque, 101, 117, 118, 226 Plasma, 25, 58, 104, 175, 177, 185, 195, 202, 203, 204, 216, 226, 231, 233, 235 Plasma cells, 177, 226 Plasma Exchange, 58, 226 Plasma protein, 175, 226, 235 Plasmacytoma, 49, 226 Plasmapheresis, 81, 83, 91, 124, 155, 226 Plasticity, 25, 227 Platinum, 212, 227

Pleural, 227, 240 Pleural cavity, 227, 240 Point Mutation, 26, 227 Poisoning, 102, 109, 186, 192, 210, 215, 218, 227 Pollen, 110, 227 Polymorphism, 57, 227 Polypeptide, 103, 104, 176, 188, 227, 229, 244, 247 Polysaccharide, 178, 185, 227 Polyvinyl Alcohol, 109, 110, 227 Pons, 173, 183, 199, 227 Posterior, 156, 179, 191, 194, 202, 214, 221, 222, 223, 227, 234 Postmenopausal, 223, 227 Postnatal, 14, 227, 237 Postoperative, 69, 227 Postsynaptic, 5, 12, 14, 25, 217, 219, 220, 227, 239 Post-synaptic, 29, 111, 227 Potentiates, 209, 227 Potentiation, 187, 227 Practice Guidelines, 146, 157, 228 Precursor, 186, 191, 194, 195, 197, 199, 221, 228, 242, 243, 244 Predisposition, 8, 228 Prednisolone, 228 Prednisone, 155, 228 Pregnancy Outcome, 133, 228 Presynaptic, 5, 6, 7, 12, 25, 32, 217, 219, 228, 239 Prevalence, 28, 52, 125, 129, 228 Primary Biliary Cirrhosis, 107, 228 Prion, 101, 118, 185, 228 Private Practice, 121, 128, 228 Progesterone, 228, 237 Progression, 25, 177, 193, 214, 228 Progressive, 12, 25, 42, 113, 115, 185, 190, 192, 194, 204, 217, 218, 219, 228, 232, 243 Prophase, 222, 228, 239 Prophylaxis, 64, 228, 243 Proprioception, 228, 236 Protease, 29, 229 Protease Inhibitors, 29, 229 Protein C, 26, 116, 175, 176, 180, 229, 236, 243 Protein Conformation, 176, 229 Protein S, 26, 124, 182, 229 Proteolytic, 189, 197, 223, 229, 233 Protocol, 5, 30, 127, 229 Protons, 30, 175, 205, 210, 229, 230 Protozoa, 215, 229


Proximal, 194, 228, 229 Psoralen, 17, 229 Psoriasis, 18, 106, 107, 229 Psychiatric, 12, 115, 122, 188, 215, 229 Psychiatry, 23, 41, 45, 47, 48, 50, 52, 62, 65, 71, 75, 200, 229, 244 Psychic, 229, 234 Psychogenic, 121, 128, 229 Psychomotor, 192, 196, 229 Ptosis, 74, 112, 229 Puberty, 230, 240 Public Policy, 145, 230 Publishing, 32, 121, 127, 128, 129, 230 Pulse, 216, 230 Pupil, 190, 193, 218, 230 Purines, 230, 234 Purpura, 107, 230 Q Quadriplegia, 129, 230 Quality of Life, 54, 230 Quiescent, 230, 246 R Radiation, 24, 173, 180, 194, 195, 197, 199, 200, 207, 208, 210, 230, 231, 246 Radiation therapy, 173, 194, 199, 210, 230, 246 Radioactive, 100, 180, 205, 208, 210, 216, 221, 222, 230, 246 Radioimmunoassay, 104, 230 Radiolabeled, 210, 230, 246 Radiological, 224, 231 Radiotherapy, 182, 210, 230, 231, 246 Ramus, 214, 231 Randomized, 4, 70, 97, 195, 231 Rape, 126, 231 Reagent, 213, 231 Receptors, Nicotinic, 221, 231 Recombinant, 31, 33, 55, 56, 105, 117, 140, 231, 244 Recombination, 202, 231 Reconstitution, 14, 231 Rectum, 182, 193, 201, 208, 211, 231 Recurrence, 182, 231 Red blood cells, 105, 197, 204, 231, 233 Red Nucleus, 179, 231 Refer, 1, 183, 188, 194, 200, 201, 212, 221, 231, 245 Reflex, 87, 92, 127, 199, 231 Reflux, 135, 198, 201, 231 Refraction, 231, 236 Refractive Errors, 193, 231 Refractory, 61, 84, 232

Regeneration, 31, 175, 231, 232 Regimen, 127, 195, 232 Regurgitation, 198, 201, 232 Relapse, 28, 70, 232 Reliability, 75, 232 Remission, 21, 49, 66, 70, 76, 182, 189, 213, 223, 231, 232 Renal cell cancer, 58, 232 Renal failure, 65, 192, 204, 232 Reproduction Techniques, 228, 232 Resorption, 53, 205, 232 Respiration, 49, 71, 178, 184, 191, 216, 232 Respirator, 232, 244 Respiratory failure, 31, 71, 232, 244 Respiratory Muscles, 156, 232 Respiratory Paralysis, 126, 232 Respiratory System, 232, 244 Restoration, 32, 231, 232, 246 Retina, 187, 211, 232, 233, 235, 243 Rheumatism, 232, 233 Rheumatoid, 11, 18, 28, 34, 81, 103, 105, 106, 107, 233 Rheumatoid arthritis, 11, 18, 28, 34, 81, 103, 105, 106, 107, 233 Ribavirin, 45, 233 Ribose, 174, 233 Ricin, 105, 233 Rickets, 129, 233 Rickettsiae, 233 Rigidity, 210, 226, 233 Risk factor, 126, 233 Rod, 180, 187, 233 Ryanodine, 37, 71, 233 S Saline, 117, 226, 233 Salivary, 193, 233 Salivary glands, 193, 233 Saponins, 91, 233, 237 Sarcolemma, 26, 233 Schizoid, 233, 246 Schizophrenia, 9, 108, 115, 122, 233, 246 Schizotypal Personality Disorder, 233, 246 Sclera, 189, 234, 243 Sclerae, 222, 234 Scleroderma, 18, 106, 107, 126, 234 Screening, 187, 234 Sebaceous, 234, 246 Second Messenger Systems, 220, 234 Secretion, 58, 81, 83, 107, 190, 205, 206, 209, 216, 234, 242, 244 Secretory, 16, 83, 219, 234, 239 Seizures, 192, 234

Index 261

Semicircular canal, 209, 234 Senile, 104, 223, 234 Sensibility, 176, 234 Sensitization, 7, 33, 234 Sensory loss, 125, 234, 240 Sequence Homology, 224, 234 Sequester, 186, 234, 239 Serine, 29, 196, 234, 243 Serologic, 207, 235 Serology, 18, 235 Serotonin, 235, 243 Serrata, 104, 187, 235 Serrated, 235 Serum Albumin, 102, 103, 230, 235 Shock, 57, 115, 235, 242 Side effect, 5, 31, 137, 140, 174, 181, 191, 194, 206, 235, 241 Signs and Symptoms, 232, 235 Skeletal, 3, 4, 5, 20, 22, 25, 26, 30, 88, 176, 187, 191, 217, 218, 235, 236, 243 Skeleton, 26, 30, 173, 211, 235 Skull, 191, 196, 210, 219, 222, 235, 240 Sleep apnea, 115, 235, 238 Small intestine, 181, 194, 205, 210, 235, 243, 245 Smallpox, 235, 244 Smooth muscle, 112, 176, 216, 217, 235, 236, 238 Social Environment, 230, 235 Sodium, 203, 216, 235 Soft tissue, 182, 222, 235, 236 Solitary Nucleus, 180, 236 Solvent, 181, 198, 203, 222, 236 Soma, 236 Somatic, 72, 127, 191, 202, 205, 215, 216, 225, 236, 244 Somatosensory Disorders, 127, 236 Sound wave, 189, 236 Spasm, 126, 220, 236 Spasmodic, 39, 122, 128, 236 Spatial disorientation, 194, 236 Specialist, 159, 193, 236 Specificity, 7, 8, 19, 23, 105, 107, 174, 183, 196, 236 Spectrin, 195, 236 Spectrum, 11, 29, 82, 183, 236, 241 Sperm, 176, 187, 227, 236 Sphincter, 126, 135, 201, 211, 212, 236 Spike, 13, 237 Spina bifida, 125, 129, 219, 237 Spinal Cord Diseases, 230, 232, 236, 237 Spinal Injuries, 129, 237

Spirochete, 237, 239 Spleen, 89, 213, 237 Spontaneous Abortion, 116, 228, 237 Sporadic, 219, 237 Stabilization, 22, 237 Standard therapy, 4, 237 Standardize, 104, 237 Stapedius, 92, 237 Stapes, 237 Steel, 187, 237 Stem cell transplantation, 14, 237 Stem Cells, 14, 107, 175, 203, 225, 237 Sterility, 191, 237 Steroid, 51, 190, 233, 237 Stillbirth, 228, 238 Stimulant, 108, 238, 244 Stimulus, 26, 194, 195, 198, 209, 210, 211, 223, 231, 238 Stomach, 135, 173, 193, 198, 201, 202, 205, 212, 218, 224, 225, 231, 235, 237, 238 Strabismus, 26, 82, 193, 238 Stress, 168, 180, 184, 190, 218, 228, 233, 238 Stricture, 22, 126, 135, 238 Stroke, 13, 16, 98, 101, 118, 122, 126, 127, 129, 131, 144, 155, 157, 211, 238 Stromal, 20, 238 Stromal Cells, 20, 238 Strychnine, 111, 238 Subacute, 15, 208, 238 Subarachnoid, 204, 210, 238 Subclinical, 208, 234, 238 Subspecies, 236, 238, 244 Substance P, 231, 234, 238 Substrate, 26, 238 Sudden death, 116, 238 Supplementation, 47, 89, 238 Support group, 159, 170, 238 Suppression, 21, 28, 33, 34, 67, 72, 110, 190, 238 Sympathetic Nervous System, 180, 239 Sympathomimetic, 174, 194, 197, 221, 239 Symptomatic, 5, 170, 239 Synapses, 5, 14, 24, 25, 29, 113, 187, 219, 220, 237, 239 Synapsis, 239 Synaptic, 6, 9, 12, 13, 15, 22, 25, 27, 29, 32, 111, 175, 217, 221, 227, 239 Synaptic Transmission, 6, 9, 15, 22, 27, 221, 239 Synaptic Vesicles, 239 Syncope, 126, 239 Synergistic, 13, 31, 239


Syphilis, 126, 220, 239 Syringomyelia, 125, 239 Systemic lupus erythematosus, 11, 18, 103, 107, 207, 239 T Tacrolimus, 63, 240 Temporal, 13, 24, 26, 29, 204, 240 Testicular, 69, 240 Testis, 203, 240 Thalamic, 179, 240 Thalamic Diseases, 179, 240 Therapeutics, 8, 11, 41, 87, 88, 89, 91, 139, 240 Thermal, 193, 221, 236, 240 Thoracic, 40, 43, 48, 49, 51, 53, 59, 62, 69, 71, 76, 193, 240, 246 Thoracoscopy, 76, 240 Threonine, 224, 234, 240 Thrombin, 229, 240 Thrombocytopenia, 107, 240 Thrombomodulin, 229, 240 Thrombosis, 190, 215, 229, 238, 240 Thrombus, 190, 208, 211, 240 Thymoma, 8, 36, 37, 38, 46, 52, 53, 56, 61, 63, 64, 65, 66, 68, 74, 75, 80, 81, 85, 89, 240 Thymus, 8, 14, 20, 33, 35, 40, 43, 44, 48, 51, 56, 73, 75, 84, 104, 124, 125, 207, 213, 240 Thymus Gland, 44, 240 Thyroid, 18, 67, 81, 169, 203, 206, 223, 240, 241, 243 Thyroid Gland, 203, 206, 223, 240, 241 Thyroid Hormones, 240, 241, 243 Thyroiditis, 106, 241 Thyrotropin, 53, 206, 241 Thyroxine, 175, 241 Tin, 225, 227, 241 Tinnitus, 9, 241, 245 Tobramycin, 74, 241 Tolerance, 16, 21, 28, 39, 72, 174, 194, 203, 207, 241 Tonic, 198, 241 Tonicity, 195, 241 Topical, 139, 179, 198, 223, 241 Torticollis, 39, 241 Toxic, iv, 111, 126, 179, 181, 191, 196, 197, 198, 207, 220, 221, 225, 226, 241 Toxicity, 5, 194, 215, 226, 241, 245 Toxicology, 146, 241 Toxins, 126, 178, 183, 196, 197, 208, 216, 241 Trachea, 211, 214, 225, 240, 241

Traction, 187, 241 Transfection, 9, 10, 25, 182, 242 Transfer Factor, 207, 242 Transferases, 203, 242 Transforming Growth Factor alpha, 242 Transforming Growth Factor beta, 242 Transforming Growth Factors, 13, 242 Translational, 15, 242 Transmitter, 6, 29, 32, 173, 194, 210, 214, 221, 239, 242 Transplantation, 14, 182, 185, 196, 207, 213, 242 Trauma, 101, 118, 129, 173, 180, 191, 192, 204, 205, 219, 240, 241, 242, 243 Tremor, 129, 242 Tricyclic, 117, 118, 242 Trigeminal, 125, 199, 242 Trochlear Nerve, 193, 242 Trochlear Nerve Diseases, 193, 242 Tropomyosin, 10, 243 Troponin, 243 Trypsin, 105, 197, 243, 247 Tryptophan, 126, 188, 235, 243 Tuberculosis, 190, 213, 243 Tubocurarine, 15, 22, 219, 243 Tumor-derived, 242, 243 Tumour, 201, 243 Tyrosine, 194, 243 U Unconscious, 206, 243 Uric, 203, 206, 230, 243 Urinary, 183, 187, 205, 208, 217, 243 Urine, 182, 191, 208, 232, 243 Uterus, 186, 192, 215, 228, 243, 244 Uvea, 243 Uveitis, 16, 243 V Vaccination, 19, 84, 243 Vaccine, 156, 174, 229, 243, 244 Vaccinia, 17, 243, 244 Vaccinia Virus, 17, 244 Vacuoles, 196, 244 Vagal, 125, 244 Vagina, 184, 186, 215, 244 Vaginitis, 184, 244 Vagus Nerve, 236, 244 Valine, 224, 244 Variola, 244 Vascular, 103, 115, 204, 208, 226, 237, 240, 243, 244 Vasculitis, 73, 244 Vasoactive, 51, 244

Index 263

Vasoactive Intestinal Peptide, 51, 244 Vasodilator, 183, 194, 244 VE, 73, 81, 244 Vector, 16, 17, 20, 116, 244 Vein, 177, 210, 221, 244 Venereal, 239, 244 Venous, 182, 185, 229, 244 Venous blood, 182, 185, 244 Ventilation, 232, 244 Ventilator, 77, 232, 244 Ventricle, 206, 230, 244, 245 Ventricular, 101, 118, 205, 245 Verapamil, 88, 245 Vertebrae, 237, 245 Vertebral, 89, 181, 226, 237, 245 Vertigo, 9, 245 Vesicular, 6, 235, 244, 245 Vestibular, 204, 245 Vestibule, 188, 209, 234, 245 Vestibulocochlear Nerve, 241, 245 Vestibulocochlear Nerve Diseases, 241, 245 Veterinary Medicine, 82, 145, 245 Villi, 205, 245 Villous, 184, 245 Vinca Alkaloids, 245 Vincristine, 80, 89, 245 Vinyl Chloride, 126, 245 Viral, 12, 116, 190, 196, 222, 245 Virulence, 179, 241, 245

Virus, 17, 56, 65, 180, 185, 190, 202, 203, 209, 226, 235, 244, 245 Viscera, 236, 245, 246 Visceral, 180, 190, 202, 244, 246 Visceral Afferents, 180, 202, 244, 246 Visual Cortex, 193, 246 Vitiligo, 18, 51, 229, 246 Vitro, 6, 15, 23, 25, 26, 28, 44, 55, 58, 69, 71, 81, 91, 196, 200, 208, 235, 240, 246 Vivo, 10, 14, 15, 17, 21, 28, 31, 55, 88, 208, 240, 246 Vocal cord, 71, 129, 225, 246 Voice Disorders, 128, 129, 246 Vomica, 238, 246 Vulgaris, 11, 106, 173, 246 W Wakefulness, 192, 246 White blood cell, 177, 208, 212, 213, 218, 221, 226, 246 Windpipe, 225, 240, 246 Withdrawal, 112, 115, 192, 246 Wound Healing, 101, 185, 214, 246 X Xenograft, 177, 246 X-ray, 16, 27, 180, 198, 200, 210, 221, 230, 231, 246 X-ray therapy, 210, 246 Y Yeasts, 184, 200, 201, 225, 246 Z Zymogen, 229, 247


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