MUSCULAR DYSTROPHY A M EDICAL D ICTIONARY , B IBLIOGRAPHY , AND A NNOTATED R ESEARCH G UIDE TO I NTERNET R E FERENCES
J AMES N. P ARKER , M.D. AND P HILIP M. P ARKER , P H .D., E DITORS
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ICON Health Publications ICON Group International, Inc. 4370 La Jolla Village Drive, 4th Floor San Diego, CA 92122 USA Copyright 2003 by ICON Group International, Inc. Copyright 2003 by ICON Group International, Inc. All rights reserved. This book is protected by copyright. No part of it may be reproduced, stored in a retrieval system, or transmitted in any form or by any means, electronic, mechanical, photocopying, recording, or otherwise, without written permission from the publisher. Printed in the United States of America. Last digit indicates print number: 10 9 8 7 6 4 5 3 2 1
Publisher, Health Care: Philip Parker, Ph.D. Editor(s): James Parker, M.D., Philip Parker, Ph.D. Publisher's note: The ideas, procedures, and suggestions contained in this book are not intended for the diagnosis or treatment of a health problem. As new medical or scientific information becomes available from academic and clinical research, recommended treatments and drug therapies may undergo changes. The authors, editors, and publisher have attempted to make the information in this book up to date and accurate in accord with accepted standards at the time of publication. The authors, editors, and publisher are not responsible for errors or omissions or for consequences from application of the book, and make no warranty, expressed or implied, in regard to the contents of this book. Any practice described in this book should be applied by the reader in accordance with professional standards of care used in regard to the unique circumstances that may apply in each situation. The reader is advised to always check product information (package inserts) for changes and new information regarding dosage and contraindications before prescribing any drug or pharmacological product. Caution is especially urged when using new or infrequently ordered drugs, herbal remedies, vitamins and supplements, alternative therapies, complementary therapies and medicines, and integrative medical treatments. Cataloging-in-Publication Data Parker, James N., 1961Parker, Philip M., 1960Muscular Dystrophy: 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: 0-597-83659-0 1. Muscular Dystrophy-Popular works. I. Title.
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Disclaimer This publication is not intended to be used for the diagnosis or treatment of a health problem. It is sold with the understanding that the publisher, editors, and authors are not engaging in the rendering of medical, psychological, financial, legal, or other professional services. References to any entity, product, service, or source of information that may be contained in this publication should not be considered an endorsement, either direct or implied, by the publisher, editors, or authors. ICON Group International, Inc., the editors, and the authors are not responsible for the content of any Web pages or publications referenced in this publication.
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Acknowledgements The collective knowledge generated from academic and applied research summarized in various references has been critical in the creation of this book which is best viewed as a comprehensive compilation and collection of information prepared by various official agencies which produce publications on muscular dystrophy. 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 MUSCULAR DYSTROPHY .......................................................................... 3 Overview........................................................................................................................................ 3 The Combined Health Information Database................................................................................. 3 Federally Funded Research on Muscular Dystrophy..................................................................... 4 E-Journals: PubMed Central ..................................................................................................... 106 The National Library of Medicine: PubMed .............................................................................. 109 CHAPTER 2. NUTRITION AND MUSCULAR DYSTROPHY ............................................................... 245 Overview.................................................................................................................................... 245 Finding Nutrition Studies on Muscular Dystrophy ................................................................. 245 Federal Resources on Nutrition ................................................................................................. 250 Additional Web Resources ......................................................................................................... 251 CHAPTER 3. ALTERNATIVE MEDICINE AND MUSCULAR DYSTROPHY ........................................ 253 Overview.................................................................................................................................... 253 National Center for Complementary and Alternative Medicine................................................ 253 Additional Web Resources ......................................................................................................... 260 General References ..................................................................................................................... 262 CHAPTER 4. DISSERTATIONS ON MUSCULAR DYSTROPHY .......................................................... 263 Overview.................................................................................................................................... 263 Dissertations on Muscular Dystrophy ...................................................................................... 263 Keeping Current ........................................................................................................................ 266 CHAPTER 5. CLINICAL TRIALS AND MUSCULAR DYSTROPHY ..................................................... 267 Overview.................................................................................................................................... 267 Recent Trials on Muscular Dystrophy ...................................................................................... 267 Keeping Current on Clinical Trials ........................................................................................... 272 CHAPTER 6. PATENTS ON MUSCULAR DYSTROPHY ..................................................................... 275 Overview.................................................................................................................................... 275 Patents on Muscular Dystrophy................................................................................................ 275 Patent Applications on Muscular Dystrophy............................................................................ 290 Keeping Current ........................................................................................................................ 298 CHAPTER 7. BOOKS ON MUSCULAR DYSTROPHY ......................................................................... 299 Overview.................................................................................................................................... 299 Book Summaries: Federal Agencies............................................................................................ 299 Book Summaries: Online Booksellers......................................................................................... 300 The National Library of Medicine Book Index ........................................................................... 304 Chapters on Muscular Dystrophy ............................................................................................. 305 CHAPTER 8. MULTIMEDIA ON MUSCULAR DYSTROPHY .............................................................. 309 Overview.................................................................................................................................... 309 Bibliography: Multimedia on Muscular Dystrophy .................................................................. 309 CHAPTER 9. PERIODICALS AND NEWS ON MUSCULAR DYSTROPHY ........................................... 311 Overview.................................................................................................................................... 311 News Services and Press Releases.............................................................................................. 311 Academic Periodicals covering Muscular Dystrophy................................................................ 317 APPENDIX A. PHYSICIAN RESOURCES .......................................................................................... 321 Overview.................................................................................................................................... 321 NIH Guidelines.......................................................................................................................... 321 NIH Databases........................................................................................................................... 323 Other Commercial Databases..................................................................................................... 325 The Genome Project and Muscular Dystrophy ......................................................................... 325 APPENDIX B. PATIENT RESOURCES ............................................................................................... 333 Overview.................................................................................................................................... 333
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Patient Guideline Sources.......................................................................................................... 333 Associations and Muscular Dystrophy...................................................................................... 339 Finding Associations.................................................................................................................. 347 APPENDIX C. FINDING MEDICAL LIBRARIES ................................................................................ 349 Overview.................................................................................................................................... 349 Preparation................................................................................................................................. 349 Finding a Local Medical Library................................................................................................ 349 Medical Libraries in the U.S. and Canada ................................................................................. 349 ONLINE GLOSSARIES................................................................................................................ 355 Online Dictionary Directories ................................................................................................... 358 MUSCULAR DYSTROPHY DICTIONARY ............................................................................. 359 INDEX .............................................................................................................................................. 439
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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 muscular dystrophy 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 muscular dystrophy, 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 muscular dystrophy, 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 muscular dystrophy. 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 muscular dystrophy, 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 muscular dystrophy. 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 MUSCULAR DYSTROPHY Overview In this chapter, we will show you how to locate peer-reviewed references and studies on muscular dystrophy.
The Combined Health Information Database The Combined Health Information Database summarizes studies across numerous federal agencies. To limit your investigation to research studies and muscular dystrophy, 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 “muscular dystrophy” (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: •
Effects of Myotonic Dystrophy and Duchenne Muscular Dystrophy on the Orofacial Muscles and Dentofacial Morphology Source: Acta Odontologica Scandanavica. 56(6): 369-374. December 1998. Summary: This article reviews two of the less rare myopathies: myotonic dystrophy (MyD) and Duchenne muscular dystrophy (DMD), and their effect on the orofacial muscles and dentofacial morphology. A high prevalence of malocclusions was found among the patients affected by these diseases. The development of the malocclusions in MyD patients seems to be strongly related to the vertical aberration of their craniofacial growth due to the involvement of the masticatory muscles in association with the possibly less affected suprahyoid musculature. Thus, a new situation is established around the teeth transversely. The lowered tongue is not in a position to counterbalance
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the forces developed during the lowering of the mandible by the stretched facial musculature. This may affect the teeth transversely, decreasing the width of the palate and causing posterior crossbite. The lowered position of the mandible, in combination with the decreased biting forces, may permit an overeruption of the posterior teeth, with increased palatal vault height and development of anterior open bite. The development of the malocclusions in DMD patients also seems to be strongly related to the involvement of the orofacial muscles by the disease. However, the posterior crossbite is not developed owing to the narrow maxillary (upper jaw) arch, as is the case in MyD patients. On the contrary, the posterior crossbite in DMD is due to the transversal expansion of the mandibular arch, possibly because of the decreased tonus of the masseter muscle near the molars, in combination with the enlarged hypotonic tongue and the predominance of the less affected orbicularis oris muscle. 2 figures. 33 references.
Federally Funded Research on Muscular Dystrophy The U.S. Government supports a variety of research studies relating to muscular dystrophy. 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 muscular dystrophy. 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 muscular dystrophy. The following is typical of the type of information found when searching the CRISP database for muscular dystrophy: •
Project Title: 2002 GORDON RESEARCH CONF. ON INTERMEDIATE FILAMENTS Principal Investigator & Institution: Coulombe, Pierre A. Professor; Biological Chemistry; Johns Hopkins University 3400 N Charles St Baltimore, MD 21218 Timing: Fiscal Year 2002; Project Start 30-JUN-2002; Project End 31-DEC-2002 Summary: (provided by applicant): The purpose of this application is to generate funds to support travel, registration, and lodging for participants in the 7th Gordon Research Conference on Intermediate Filaments, which will be held June 30th-July 5th 2002 at Roger Williams University in Bristol, Rhode Island. Intermediate filaments (IFs) are prominent components of the cytoskeleton and nuclecoskeleton in higher eukaryotes. In the public draft of the human genome, there are greater than 67 functional genes encoding IF-forming polypeptides. These genes are typically regulated in a cell typespecific manner and highly conserved in mammalian genomes. A general function of IF polymers is to endow cells and tissues with the mechanical resilience they need to withstand various types of physical and non-physical stresses. Defects in IF proteins
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Healthcare projects are funded by the National Institutes of Health (NIH), Substance Abuse and Mental Health Services (SAMHSA), Health Resources and Services Administration (HRSA), Food and Drug Administration (FDA), Centers for Disease Control and Prevention (CDCP), Agency for Healthcare Research and Quality (AHRQ), and Office of Assistant Secretary of Health (OASH).
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underlie a vast number of genetically determined fragility disorders involving epithelia (e.g., skin, oral, and eye blistering diseases; inflammatory bowel diseases; liver disorders), muscle (e.g., cardiomyopathies; muscular dystrophy), neural tissue (e.g., amyotrophic lateral sclerosis; Alexander's diseases), and even adipose tissue (e.g., lipodystrophy). IFs fulfill other functions in a differentiation and context-dependent fashion, including promoting specific cytoarchitecture, tissue response to injury and other forms of stress, response to apoptotic signals, signaling, and nuclear architecture and gene expression (lamins). This Gordon Research Conference (GRC) is said to represent the only regular meeting devoted to IF biology. It brings together participants of junior and senior rank from all over the world who are studying IFs from a wide variety of angles. This GRC has traditionally fostered a free-flowing exchange of novel ideas, tools, and reagents, and facilitated the establishment of productive collaborations. The Program for the 2002 edition of the Conference has been finalized. The following major themes will be covered: 1) Atomic structure of IFs: From models to reality; 2) Regulating IF assembly and dynamics in vivo; 3) IFs and cell and tissue mechanics; 4) IF-associated cytolinkers: Mechanical integration and other functions; 4) Function of IFs in C. elegans, in muscle and neurons; 5) Functions of keratins in epithelia: Beyond scaffolding?; and 6) Laminopathies, lamin functions, and the nuclear envelope. In addition, there will be a special "Perspectives" session and a platform session dedicated to the discussion of posters. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •
Project Title: A RESOURCE FOR MAGNETIC RESONANCE AND OPTICAL RESEARCH Principal Investigator & Institution: Leigh, John S. Professor of Radiology; Radiology; University of Pennsylvania 3451 Walnut Street Philadelphia, PA 19104 Timing: Fiscal Year 2001; Project Start 30-SEP-1984; Project End 31-AUG-2004 Summary: The regional resource develops innovate magnetic resonance (MR) and optical technologies for biomedical research. These technologies are driven by both basic and clinical research collaborators in the biomedical field to address specific clinical problems and to further fundamental understanding of biophysical, structural, and functional properties of biological systems in vivo. In conjunction with its collaborators, the resource has developed four broad areas of core research. The first core deals with the use of multinuclear MR techniques to study the structural and metabolic properties of cartilage, brain, and muscle, with direct application to osteoarthritis, stroke, and muscular dystrophy. This core also investigates the use of multinuclear MR to monitor the efficacy of gene therapy in the setting of muscle disease. In the second core, the resource presents developments and improvements in quantitative perfusion and diffusion imaging, in comparison to PET. The third core deals with innovative techniques for quantitative structural imaging of multiple organ systems. These techniques include MR of hyperpolarized gases, novel contrast generation using zeroquantum coherences, and imaging of tissue microstructure. The fourth core focuses on combining optical and MR imaging techniques for the study of neurophysiology, peripheral vascular disease, and breast cancer. Technology developed by these cores will drive sixteen collaborative projects in the study of various normal and pathological tissues. Services provided by the resources include access to the 2 Tesla research magnet, coil-building facility, in- magnet exercise devices, and computer software developed by the resource. The resource also maintains an active training program consisting of seminars, MR courses, workshops, training lectures, practical training in MR and optical methods, and disseminates its research through news letters,
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presentations at national and international conferences, and a resource web site that provides access to all publications and software packages developed by the resource. The research resource remains committed to intellectual interchange and the interdisciplinary pursuit of basic and clinical medicine. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •
Project Title: ACQUISITION SPECTROMETER
OF
A
NANOFLOW
ION
TRAP
MASS
Principal Investigator & Institution: Wysocki, Vicki H. Professor; Chemistry; University of Arizona P O Box 3308 Tucson, AZ 857223308 Timing: Fiscal Year 2003; Project Start 01-APR-2003; Project End 31-MAR-2004 Summary: (provided by applicant): This proposal requests a Thermo Finnigan ProteomeX DECAP-51000 Integrated Workstation, an ion trap mass spectrometer equipped with LC pumps, a 10 port switching valve, strong cation and reversed phase columns for multidimensional chromatography, and a nanospray probe. This instrument will serve the needs of a number of University of Arizona bioscience researchers. The major users and their applications for the instrumentation are (1) Samuel Ward, Molecular and Cellular Biology, Study of signaling pathways during cell differentiation in the Nematode C.elegans, genes are homologeous to human disease genes linked to Alzheimer's and muscular dystrophy; (2) Brian Larkins, Plant Sciences, College of Agriculture and Life Sciences, Identificationand Analysis of Proteins Required for Improved Maize Protein Nutritional Quality; (3) M. Halonen/D. Vercelli/F. Martinez/M. Cusanovich, Center for Respiratory Sciences, Transcription Factors that Bind Regulatory Elements in the Immunoglobulin G4 Germline Promoter, the IL-13 Promoter, and the CD 14 Promoter; Cellular and Molecular Mechanisms of Asthma (4) Elizabeth Vierling, Molecular and Cellular Biology, Molecular chaperone function; expression and function of cytoplasmic organelle and heat shock proteins, the pathways studied are critical to normal cell function; (5) Carol Dieckmann, Biochemistry, Identification of Mutations in Genes Coding for Major Polypeptides in the Chlamydomonas Eyespot; (6) Thomas Baldwin, Biochemistry, Pulsed Alkylation MS to Investigate Protein Folding in Bacterial Luciferase; (7) Vicki Wysocki, Chemistry, Mechanisms and Energetics of Peptide Dissociation, this work is directly applicable to the identification of proteins from biological organisms. Modern protein research cannot be accomplished without mass spectrometry. The access to a dedicated microflow LCmass spectrometer with a nanospray probe to characterize samples that are not amenable to analysis with the current mass spectrometry facility instruments is critical to the maximum productivity and success of these projects. The University has made a strong commitment to the project by by renovating space for a new "branch" mass spectrometry laboratory that is located in Biosciences, by hiring a full time Ph.D. biological mass spectrometry specialist (about $60,000 per year), by providing funds for a Director of Proteomics (about $80,000/year) and a technician (about $35,000/year) to help with sample preparation, and by providing cost sharing in the amount of $75,000. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •
Project Title: ACTININ ASSOCIATED LIM PROTEIN & FSH MUSCULAR DYSTROPHY Principal Investigator & Institution: Bredt, David S. Professor; Physiology; University of California San Francisco 500 Parnassus Ave San Francisco, CA 94122 Timing: Fiscal Year 2001; Project Start 01-FEB-1996; Project End 31-JAN-2003
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Summary: Disruptions of the myofiber cytoskeleton underlie several genetic muscular dystrophies, including Duchenne and Limb-girdle muscular dystrophies. In addition to these dystrophin-related disorders, certain inherited muscular dystrophies are due to mutations in cytoskeletal proteins that do not interact with the dystrophin complex. Identification of the responsible proteins and clarification of mechanisms that regulate the myofiber cytoskeleton are therefore critical goals. Recent molecular cloning studies have identified actinin-associated LIM protein (ALP), which is a novel component of the muscle cytoskeleton. ALP contains a PDZ protein motif that is also present in certain dystrophin-associated proteins, yet ALP does not interact with dystrophin. Instead ALP binds to actinin, a structural homologue of dystrophin, and ALP associates with actinin at the Z-lines of skeletal muscle. Chromosomal mapping studies show that ALP occurs in 4q35, within 7 Mb of the telomeric region that is deleted in facioscapulohumeral muscular dystrophy (FSHD), the most common autosomal muscular dystrophy. ALP is the only muscle-specific gene yet found to map in this region. Therefore, a possible role for ALP in the pathogenesis of FSHD must be explored. We now propose to characterize the molecular interaction of ALP with actinin and to determine the composition and function of the ALP-associated complex at the Z-lines. To help assess whether ALP participates in FSHD, we will determine whether ALP expression is altered in muscle biopsies from diseased patients. Because FSHD is a dominant disease, it is likely that only one allele of the responsible gene(s) will be abnormal. To address this, we will also evaluate allele-specific expression of ALP in FSHD muscle samples. Because complex genetics underlie FSHD, studies of human tissues alone may not decisively identify the responsible gene(s). We will therefore target disruption of ALP in stem cells and breed mice that lack ALP protein. Muscle development, histology and function will be carefully evaluated in the ALP mutants. Assembly of the ALP-associated protein complex at the Z-lines will also be evaluated in the mutants. If these mutant mice manifest signs that resemble FSHD this would implicate a role for ALP in this disease and the mice would provide a unique animal model. The proposed studies will lead to a better understanding of formation and function of the myofiber cytoskeleton and may provide insight in the pathogenesis and treatment of FSHD. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •
Project Title: ADENO-ASSOCIATED VIRUS (AAV) VECTORS TO IMPROVE MATURE MUSCLE FUNCTION Principal Investigator & Institution: Xiao, Xiao; Associate Professor; University of Pittsburgh at Pittsburgh 350 Thackeray Hall Pittsburgh, PA 15260 Timing: Fiscal Year 2001; Project Start 01-APR-2001; Project End 31-MAR-2002 Summary: Muscular dystrophies are a relatively common group of inherited degenerative muscle disease. Most types are caused by mutations in genes coding for membrance associated proteins in muscle. Duchenne muscular dystrophy (DMD) and limb-girdle muscular dystrophy (LGMD) often manifest themselves in young ages and lead to early morbidity with no currently available effective treatment. These diseases are recessive, loss-of- function of the corresponding gene product, which makes them suitable for gene replacement therapy. Recombinant adeno-associate virus (rAAV) is one promising gene replacement vector based on defective human parvoviruses. The rAAV system has attracted attention due to its non- pathogenicity, genomic integration, transduction of quiescent cells, and apparent lack of cellular immune reactions. In contrast to other viral vectors, rAAV is capable of efficiently bypassing the myofiber basal lamina and transducing mature muscle cells. We have demonstrated that rAAV vectors harboring a foreign gene can achieve highly efficient and sustained gene
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expression in mature muscle of immunocompetent animals for more than 1.5 years without detectable toxicity. Recently, significant improvement in vector production methodology has made it possible to generate high titer and high quality rAAV vectors completely free of helper adenovirus contamination. However, no experiments using rAAV vectors to restore the functional deficits in muscle tissue itself have been reported to date. Here, we propose to take advantage of rAAV vector system, to test two therapeutic genes (delta-sarcoglycan and a highly truncated dystrophin), under the control of two different promoter systems (viral/CMV or muscle- specific/MCK), in two relevant animal models of muscular dystrophies (Bio14.6 hamster for LGMD and mdx mouse for DMD). Two distinct vector delivery methods, local intramuscular infection versus systemic delivery will be utilized. We have the following three hypotheses to be tested. 1): muscle deficient in delta-sarcoglycan can be functionally rescued by genetic complementation using intramuscular AAV vector injection in the LGMD hamster model. 2) systemic delivery of the delta-sarcoglycan gene can be mediated by rAAV vectors through intra-artery or intra-ventricle injection. 3) a dystrophin mini-gene lacking the central rod domain will improve the function of dystrophin-deficient muscle when delivered into dystrophic mdx mice by AAV vectors. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •
Project Title: ANALYSIS AND MODULATION OF IMMUNITY IN GENE THERAPY Principal Investigator & Institution: Clemens, Paula R. Associate Professor; Neurology; University of Pittsburgh at Pittsburgh 350 Thackeray Hall Pittsburgh, PA 15260 Timing: Fiscal Year 2001; Project Start 01-JAN-1999; Project End 31-DEC-2003 Summary: (Abstract): Therapeutic gene transfer is a logical approach to the treatment of inherited genetic deficiency diseases, many of which have no other adequate treatment. However, persistent expression of the therapeutic gene in the target tissue and/or the capability of repeat administration will be required. To date, adenoviral (Ad) vectormediated gene transfer trials have resulted in an immune response that eliminates the therapeutic protein. This immunity may be due either to the expression of the therapeutic protein itself, to Ad proteins or both. The future success of human gene therapy trials using the Ad vector as a vehicle will likely depend on a comprehensive understanding of this immune response and novel strategies to modulate it. Although the therapeutic protein to be provided by a gene therapy vector is a self-protein in healthy individuals, the patients who would be treated by gene transfer lack this selfprotein due to a germ-line mutation (a null mutant). Examples include Factor IX deficiency, cystic fibrosis and Duchenne's muscular dystrophy (DMD). DMD provides an excellent model with which to study gene transfer treatment for an inherited protein deficiency because the mutant gene and defective protein are known, the target tissue is easily accessible and the mdx mouse strain, which models human DMD, is readily available. The investigators recently have described the development and use of a novel high-capacity Ad vector that has all viral genes removed and can accommodate 30 kb of insert DNA. This vector is the most promising to date for decreasing the immunity induced by therapeutic Ad vector- mediated gene delivery; no AD antigens are expressed from the vector, and the use of a muscle-specific promoter should reduce antigen presentation by professional antigen presenting cells. The five aims of this application will lead to the characterization and modulation of the immune response induced by therapeutic gene delivery to skeletal muscle. The first group (Aims 1, 2 and 3) will analyze the immune response to specific antigens. The second group (Aims 4 and 5) has as a common thread the modification of vector characteristics to improve high-
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capacity Ad vector-mediated gene delivery to muscle by modulating the immune response to the antigens studies in Aims 1-3. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •
Project Title: ANALYSIS OF ASKS, COMPONENTS OF SCF UBIQUITIN-LIGASES Principal Investigator & Institution: Gingerich, Derek J. Horticulture; University of Wisconsin Madison 750 University Ave Madison, WI 53706 Timing: Fiscal Year 2003; Project Start 01-MAY-2003; Project End 30-APR-2006 Summary: (provided by applicant): The majority of targeted protein degradation in the cell is performed by the ubiquitin (Ub)/26S proteasome pathway, which is highly conserved in all eukaryotic species. In this pathway, proteins to be degraded are covalently tagged with multiple ubiquitins, which serves as the degradation signal, by the sequential action of three enzymes. The final enzyme in this process, the E3 Ubligase, binds the target and catalyzes attachment of the Ub moiety to the protein. This proteolytic pathway has been shown to be important for a wide range of cellular processes, including cell cycle progression, DNA repair, hormone signal transduction and receptor regulation, and degradation of abnormal proteins. It also has been implicated genetically in a number of diseases, including cancer, Parkinson's disease, and muscular dystrophy, arguing for the need to study this pathway in more detail. One subfamily of E3 Ub-ligases is the SCF (Skpl, Cullin/Cdc53, F-box protein) complex. In Arabidopsis thaliana 19 genes encode Skpl homologues and 694 genes encode F-box proteins. Presumable the 19 ASKs combine with the 694 F-box proteins to generate a hierarchy of SCF complexes capable of labeling a wide range of targets. I propose a line of research that studies the functions of the ASK genes in Arabidopsis. By using genetic, biochemical, and cytological approaches to characterize the function of ASKs, I hope to better understand the roles that SCF complexes play in various cellular processes in Arabidopsis. The remarkable conservation of the Ub/26S proteasome pathway means these studies should contribute to our understanding of its function in all eukaryotes, which could lead to new strategies to affect the pathway for medicinal or agricultural benefit. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen
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Project Title: ANALYSIS OF DELTA-SARCOGLYCAN IN CARDIOMYOPATHY Principal Investigator & Institution: Allikian, Michael J. Medicine; University of Chicago 5801 S Ellis Ave Chicago, IL 60637 Timing: Fiscal Year 2001; Project Start 15-SEP-2001 Summary: Mutations in the dystrophin-associated proteins, gamma- and deltasarcoglycan, have been shown to cause both cardiomyopathy and muscular dystrophy in humans. It has recently been shown that dominant negative mutations in deltasarcoglycan can cause dilated cardiomyopathy in humans. This is in contrast to the null mutations that have previously been shown to produce muscle and heart degeneration in humans and mice. Delta-sarcoglycan is a 35 kD type II transmembrane protein. Delta sarcoglycan is expressed in heart, skeletal and smooth muscle and forms an integral part of the sarcoglycan complex. We plan to study these dominant negative mutations in cell culture as well as transgenic mice in order to ascertain their effects on other components of the dystrophin glycoprotein complex including dystrophin, laminin, filamin and nitric oxide synthase. We are proposing to study heterozygous mutations in deltasarcoglycan because these mutations likely result in disrupted interactions within the j dystrophin-glycoprotein complex. Therefore, we will gain an increased understanding
10 Muscular Dystrophy
of the etiology of dilated cardiomyopathy through the investigation of deltasarcoglycan. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •
Project Title: ANALYSIS OF THE MOLECULAR AND FUNCTIONAL ROLE OF D4Z4 Principal Investigator & Institution: Tupler, Rossella G. Research Assistant Professor; Biochem and Molecular Biology; Univ of Massachusetts Med Sch Worcester Office of Research Funding Worcester, MA 01655 Timing: Fiscal Year 2001; Project Start 30-SEP-2001; Project End 31-AUG-2004 Summary: (provided by applicant): Facioscapulohumeral muscular dystrophy (FSHD) is a hereditary neuromuscular disorder of unknown cause, characterized by an insidious onset and progressive course. It has been causally related to deletions of tandemly arrayed 3.3 kb repeat units (D4Z4) on chromosome 4q35 possibly affecting expression of nearby genes by a process analogous to position effect variegation (PEV). Interestingly, we observed over-expression of 4q35 genes in FSHD muscles. We discovered that HMG2, a non-histone nuclear protein involved in heterochromatin formation, is specifically associated to a 27 bp element within D4Z4. We demonstrated that HMG-2 mediates gene silencing at 4q35 and its removal increases gene expression levels, explaining the observed over-expression of those genes in FSHD dystrophic muscles. Our experiments suggest that D4Z4 maintains 4q35 silencing by interacting with a transcriptional repressive complex. It is thus plausible that reduction of repeat number to a critical threshold might induce the over-expression of proximal genes and trigger FSHD pathogenesis. The long term of our studies is to elucidate the FSHD pathogenic process through the analysis of the molecular events occurring at D4Z4. To this aim we will characterize the D4Z4 repressing complex through biochemical purification and functional analysis. We will investigate the effects of D4Z4 deletion on 4q35 gene expression in normal and affected muscle tissues. We expect this analysis to provide a number of genes specifically deregulated in FSHD. Subsequently we will analyze the biological functions of candidate genes in appropriate model organisms. Silencing at 4q35 might also be hampered by abnormalities of repressing complex proteins. Therefore it is possible that non-4q35 FSHD cases might be related to mutations of genes coding those proteins. To this aim, we will screen for mutations in candidate genes all the myopathic individuals referred us for FSHD in which no D4Z4 deletions were detected. Our studies will provide relevant information to understand the molecular basis of FSHD and to develop effective therapeutic strategies. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen
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Project Title: ANALYSIS OF TORSIN PROTEIN FUNCTION IN C. ELEGANS Principal Investigator & Institution: Caldwell, Guy A. Biological Sciences; University of Alabama in Tuscaloosa Tuscaloosa, AL 35487 Timing: Fiscal Year 2003; Project Start 01-FEB-2003; Project End 31-JAN-2006 Summary: (provided by applicant): Dystonia is estimated to be six times more prevalent than Huntington's Disease, ALS, or Muscular Dystrophy. However, as few as 5% of the over 350,000 persons in North America estimated to be affected have been correctly diagnosed and are under treatment (NIH Budget Office). The most severe early-onset form of this disorder has been linked to a mutation in a human gene named TOR1A that encodes torsinA, a protein that is also localized to inclusions in the brains of Parkinson's patients termed Lewy bodies. While a causative genetic mutation has been identified,
Studies 11
the cellular mechanisms of pathogenesis underlying dystonia remain unknown. We are applying the advantages of the model organism, Caenorhabditis elegans, towards a detailed analysis of two specific torsin-related gene products in this nematode. The chromosomal positioning of these genes suggests that they may represent a functionally co-expressed unit and preliminary studies from our laboratory indicate they act neuronally. Phylogenetic analysis of the torsin family indicates these proteins share distant sequence similarity with the functionally diverse AAA+ family of proteins. We have determined that ectopic overexpression of a C. elegans torsin homolog results in a reduction of polyglutamine repeat-induced protein aggregation in a manner similar to that previously reported for molecular chaperones. The suppressive effects of torsin overexpression quantitatively persisted as animals aged. Antibody staining of transgenic animals using antisera specific to TOR-2 indicated this protein was highly localized to sites of protein aggregation. We propose to extend these preliminary studies through a combination of reverse genetic approaches designed to investigate the cellular role of torsin proteins in the nematode. The specific aims of the proposed project include: 1) to determine what phenotypes are associated with C. elegans torsin homologues; 2) to define sites of C. elegans torsin protein function; and 3) to determine potential effectors of torsin activity. These studies will further our understanding of the molecular mechanisms responsible for early-onset torsion dystonia. Moreover, the aberrant protein deposition associated with diverse neurodegenerative disorders like Parkinson's Disease and those caused by polyglutamine expansion such as Huntington's Disease warrants further investigation of any putative neuroprotective effects of torsins. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •
Project Title: ASTROCYTE DEVELOPMENT
DYSTROGLYCAN
COMPLEXES
IN
BRAIN
Principal Investigator & Institution: Moore, Steven A. Professor; Pathology; University of Iowa Iowa City, IA 52242 Timing: Fiscal Year 2001; Project Start 20-APR-2001; Project End 31-MAR-2004 Summary: (Applicant's abstract): The dystrophin-glycoprotein complex (DGC) is a well characterized array of cytoplasmic, membrane spanning, and extracellular matrix proteins that form a critical linkage between the cytoskeleton and the basal lamina of striated muscle. Within the central nervous system (CNS), similar dystroglycan linkages to basal laminae are present at two interfaces formed by astrocytes: (1) foot processes abutting on cerebral blood vessels and (2) foot processes that form the glia limitans at the pial surface of the brain. The former interface is critical for formation and maintenance of the blood-brain barrier, while the latter is likely to play important roles in anchoring radial glia during neuronal migration. Basal lamina abnormalities at the glia limitans have been identified in some forms of congenital muscular dystrophy in humans (e.g. Fukuyama muscular dystrophy) and basal lamina disruption at the glia limitans leads to abnormal CNS development in animal models. In this proposal, we will focus attention on the central protein in the astrocyte-basal lamina linkage, dystroglycan. Our Specific Aims propose to identify protein elements of the astrocytedystroglycan complex, elucidate protein interactions within the complex, and demonstrate the importance of the astrocyte dystroglycan complex during CNS development. Through the use of Cre-lox methodology, we plan to create a novel murine model of CNS developmental disorders. This project is a cross-discipline collaboration among investigators with expertise in clinical neuropathology and in basic neuroscience, molecular biology, cell biology, and membrane physiology who are uniquely situated to carry out the proposed studies. Aim 1: To define the composition of
12 Muscular Dystrophy
the astrocyte-dystroglycan complex(es), we will test the hypothesis that one-or-more dystroglycan complexes are present in astrocytes using a combination of biochemical and immunohistochemical methods. These studies will utilize tissue sections and cultured astrocytes from wild type mice and mice with naturally occurring or genetically engineered mutations of one or more of the DGC components known to be expressed in astrocytes. Aim 2: To create a new model of CNS developmental abnormalities by selectively disrupting the astrocyte-dystroglycan complex. Dystroglycan +/-, dystroglycan lox/lox, and GFAP-Cre mice will be bred to produce GFAP-Cre/dystroglycan lox/- and GFAP-Cre/dystroglycan lox/lox mice. This strategy should disrupt the astrocyte DGC beginning in the latter half of embryonic development. We believe this strategy will produce mice with neuronal migration and cerebrovascular defects. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •
Project Title: BIGLYCAN AS A THERAPEUTIC FOR MUSCULAR DYSTROPHY Principal Investigator & Institution: Mcquillan, David J.; Lifecell Corporation 1 Millenium Way Somerville, NJ 08876 Timing: Fiscal Year 2002; Project Start 15-SEP-2002; Project End 14-MAR-2003 Summary: (provided by applicant): The overall goal of this proposal is to use animal models to test the efficacy of biglycan as a protein therapeutic for muscular dystrophy. Duchenne's muscular dystrophy (DMD) is a heritable disease that affects approximately 1 in 3,500 boys. These children are usually wheelchair-bound by age 12 and rarely survive past their early twenties. There are currently no effective treatments for the underlying pathology of DM0. The molecular pathogenesis of Duchenne's and many other muscular dystrophies has been traced to a specialized ensemble of proteins at the muscle cell surface known as the dystrophin-associated protein complex (DAPC). Mutation of dystrophin leads to disruption in the organization of the DAPC. The resulting failure of DAPC function results in muscle cell damage and loss. We have recently discovered that the extracellular matrix molecule biglycan is expressed at the muscle cell surface and binds, by distinct mechanisms, to the ectodomains of three core constituents of the DAPC: alpha-dystroglycan, aipha-sarcoglycan and gammasarcoglycan. These molecular interactions indicate that biglycan can bridge the component subcomplexes of the DAPC and thus coordinate and stabilize the entire complex from outside the cell. Indeed, biglycan null (bgn-/o) mice display a dystrophic phenotype as evidenced by weakened muscle cell membranes and cell death. These observations suggest that biglycan could serve as a therapeutic to stabilize the DAPC from its extracellular aspect when dystrophin is absent. Biglycan thus represents a new path for developing therapies for muscular dystrophies. Importantly, since the biglycan-DAPC interactions are wholly extracellular, biglycan can be introduced to the muscle by systemic delivery of the purified recombinant protein. This program will utilize unique production methods to produce sufficient quantities of high quality biglycan,.and test efficacy in several animal models of muscular dystrophy. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen
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Project Title: DYSTROPHY
BIOENGINEERING
RESEARCH
PARTNERSHIP--MUSCULAR
Principal Investigator & Institution: Sweeney, H. Lee. Professor and Chairman; Physiology; University of Pennsylvania 3451 Walnut Street Philadelphia, PA 19104 Timing: Fiscal Year 2001; Project Start 20-SEP-2000; Project End 31-AUG-2005
Studies 13
Summary: (Applicant's abstract verbatim) The goal of this BRP is to utilize a number of aspects of bioengineering in order to develop tools and therapeutics for the treatment and monitoring of muscular dystrophies. The project is collaboration between three investigators and includes the following areas of bioengineering relevant to the PA: 1) cell and tissue engineering, 2) imaging and 3) therapeutics. Collectively we will delineate factors that when expressed in muscle may slow that rate of degeneration that is concomitant with either the complete (Duchenne muscular dystrophy) or partial (Becker muscular dystrophy) loss of dystrophin. These studies will utilize the mdx mouse as the animal model for dystrophin deficiency. The long-term goal is to gain the understanding and tools necessary to develop adeno-associated (AAV)-based gene therapy for Duchenne and Becker muscular dystrophies. Three parallel lines of investigation (each directed by one of the three investigators) are proposed: Section 1: a dissection the mechanical role of dystrophin and muscle adhesion proteins (directed by Dennis Discher); Section 2: an assessment of the functional benefits of restoring adhesion molecules to dystrophic muscle using recombinant adeno-associated virus gene delivery (directed by H. Lee Sweeney, Ph.D.); and Section 3: development of non-invasive methods for monitoring therapeutic benefits of dystrophin gene transfer (directed by Glenn Walter, Ph.D.). Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •
Project Title: CAVEOLIN-3 AND MUSCULAR DYSTROPHY Principal Investigator & Institution: Lisanti, Michael P. Molecular Pharmacology; Yeshiva University 500 W 185Th St New York, NY 10033 Timing: Fiscal Year 2001; Project Start 01-APR-2000; Project End 31-MAR-2005 Summary: The long-term objective of this proposal is to understand the role of muscle caveolae and caveolin-3 i) in normal muscle development; and ii) in the pathogenesis of muscle dystrophy. Caveolae are "little caves" at the surface of cells. It has been proposed that caveolae function as message centers" for regulating signal transduction. Caveolin3, a muscle-specific caveolin-related protein, is the principal structural protein of caveolae membrane domains in striated muscle cell types (cardiac and skeletal). Recently, we identified a novel autosomal dominant form of limb girdle muscular dystrophy (LGMD-1C) in humans that is due to mutations within the coding sequence of the human caveolin-3 gene (3p25). The aim of this proposal is to test the hypothesis that caveolin-3 expression is important for normal muscle development and that changes in caveolin-3 expression (either up-regulation or down-regulation) can result in muscular dystrophy phenotype. In order to test this hypothesis, we will use a variety of complementary in vivo approaches, such as the use of caveolin-3 anti-senses in cultured cells and the development of mouse animal models. The specific aims of the project are: 1) To determine the role of caveolin-3 mutations in the pathogenesis of LGMD- 1C. We will examine the phenotypic behavior of LGMD-1C mutations of caveolin-3 after heterologous expression in NIH 3T3 cells, as compared with wild-type caveolin-3; 2) To develop transgenic mouse models that over wild-type caveolin-3 and LGMD-1C mutant forms of caveolin-3. We will over-express wild type and LGMD-1C mutant forms of caveolin- 3 as transgenes in mice and assess their effects on skeletal muscle. As caveolin3 levels are up-regulated in Duchenne's muscular dystrophy, these experiments will help us evaluate if caveolin-3 up-regulation contributes to the pathogenesis of this diseases; and 3) To examine if caveolin-3 expression is required for normal muscle development. Using an anti-sense approach, we will abrogate caveolin-3 expression in C2C12 cells, a skeletal myoblast cell line that differentiates in culture. We will then assess the effects of caveolin-3 down-regulation on C2C12 myoblast fusion and myotube
14 Muscular Dystrophy
formation. In addition, through a targeted gene disruption approach, we will create and characterize "knock-out" mice that lack caveolin-3 gene expression. It is expected that these studies will contribute fundamen6tal knowledge toward understanding the role of muscle cell caveolae in normal muscle development and muscular dystrophy. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •
Project Title: CELLULAR SIGNALING AND MUSCULAR DYSTROPHIES Principal Investigator & Institution: Rando, Thomas A. Assistant Professor; Neurology & Neurological Scis; Stanford University Stanford, CA 94305 Timing: Fiscal Year 2001; Project Start 15-AUG-2001; Project End 14-AUG-2006 Summary: The muscular dystrophies are devastating diseases of progressive weakness due to apoptotic and necrotic death of muscle cells. The normal cellular mechanisms regulating cell survival that are disrupted in these diseases are not well understood. Several forms of muscular dystrophy are due to abnormalities of membrane proteins and protein complexes, such as integrins and caveolins, that are known to regulate cellular signaling pathways in general, and cell survival signaling in particular, in different cell types. Others, such as those due to dystrophin mutations, are due to abnormalities of protein complexes that are postulated to transduce signals from the extracellular matrix into the cell. We will focus on three proteins/protein complexes that cause muscular dystrophies when a component of the complex is deficient or defective alpha5beta1 integrin, caveolin-3, and the dystrophin-glycoprotein complex (DGC). The experiments of this proposal are designed to explore the cellular signaling processes the promote cell survival via these membrane protein complexes, and the mechanisms of cell death when these complexes are disrupted. For studies of integrin signaling, we will use cells genetically deficient in alpha5 integrin to test which isoforms of protein kinase C are important in alpha5 integrin mediated muscle cell survival (based on our previous finding of the importance of protein kinase C in this process). We will explore how alpha5 integrin deficiency leads to muscle cell death by testing for dysregulation of cell survival/cell death pathways involving the Bcl family of proteins, cytochrome c release from mitochondria, and activation of the caspase cascade. We will also examine the role of activation of the PI3 kinase/Akt pathway in alpha5 integrin- mediated muscle cell survival. For studies of the DGC, we will investigate how disruption (genetically, by antibody inhibition, or by antisense expression) of the association of the complex with the extracellular matrix may lead to cell death. In these studies, we will also examine cells for dysregulation of cell survival mechanisms involving Bcl family proteins since apoptosis has been shown to be the earliest change in muscle associated with dystrophin deficiency. For studies of dystrophies due to caveolin-3 mutations, we will render muscle cells functionally deficient in caveolin-3 using both antisense methods and dominant negative inhibitors. We will study the mechanisms by which caveolin-3 deficiency lead to muscle cell death, and we will test whether these mechanisms involve the disruption of either normal integrin signaling or signaling through the DGC. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen
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Project Title: CHARACTERIZATION OF MYOSTATIN AND GDF-11 Principal Investigator & Institution: Lee, Se-Jin; Associate Professor; Molecular Biology and Genetics; Johns Hopkins University 3400 N Charles St Baltimore, MD 21218 Timing: Fiscal Year 2003; Project Start 08-DEC-1997; Project End 30-NOV-2007 Summary: (provided by applicant): Myostatin (MSTN) and GDF-11 are secreted proteins that we originally identified in a screen for novel growth and differentiation
Studies 15
factors related to transforming growth factor-Beta (TGF-B). The predicted sequences of MSTN and GDF-11 are greater than 90% identical in the mature, C-terminal portion of the proteins, and together, these molecules form their own subgroup within the larger TGF-B superfamily. We have been using a variety of in vitro and in vivo approaches, including gene targeting in mice, to attempt to identify the biological functions of MSTN and GDF-11. We have shown that mice lacking MSTN have dramatic and widespread increases in skeletal muscle mass, suggesting that MSTN normally functions as a negative regulator of muscle growth. We have also shown that mice lacking GDF-11 have extensive homeotic transformations of the axial skeleton, suggesting that GDF-11 normally acts as a global regulator of axial patterning. The overall aim of this proposal is to further investigate the biological functions of these molecules and the mechanisms by which their activities are regulated. The specific aims are: to investigate the functional redundancy of MSTN and GDF-11; to analyze the effect of postnatal loss of MSTN and GDF-11 on skeletal muscle mass; to further characterize the role of activin type II receptors in regulating MSTN and GDF-11 signaling; to identify other components of the MSTN and GDF-11 receptor complex; to further investigate the role of follistatin in regulating MSTN and GDF-11 activity; and to investigate the mechanism by which latent MSTN is activated. Taken together, these studies will provide important insights into the normal biological functions of these molecules and may suggest new strategies for modulating the activities of these molecules for human therapeutic applications in muscle wasting diseases, such as muscular dystrophy and cachexia, andmetabolic diseases, such as obesity and type II diabetes. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •
Project Title: CLINICAL AND MOLECULAR ANALYSIS OF OREGON EYE DISEASE Principal Investigator & Institution: Pillers, De-Ann M. Associate Professor; Pediatrics; Oregon Health & Science University Portland, OR 972393098 Timing: Fiscal Year 2001; Project Start 30-SEP-1994; Project End 31-MAY-2003 Summary: (Verbatim from applicant's abstract): The title of the application is "Clinical and molecular analysis of Oregon Eye Disease." A more current title would be "Dystrophin and the retina." During the initial application period, it was shown that dystrophin, the product of the Duchenne muscular dystrophy (DMD) gene, is involved in retinal electrophysiology. Three lines of evidence support this. The position of a mutation in the DMD gene predicts the ERG phenotype, and abnormal ERGs were correlated in large part with mutations of a specific isoform of dystrophin, Dp260, which was identified and cloned from retina. New data suggests that other muscular dystrophies are associated with defects in retinal electrophysiology. Specifically, mouse models with defects in laminin-2 have abnormal ERGs. Dystrophin is part of a cellular continuum from the actin cytoskeleton to laminin and the extracellular matrix via a transmembrane group of proteins known as dystrophin-associated glycoproteins (DGC). It is hypothesized that defects in the interaction between retina-specific isoforms of dystrophin and the DGC result in altered retinal electrophysiology and an abnormal ERG. It is proposed that the retinal isoform Dp260 plays an important role in retinal electrophysiology by interfacing with the DGC at the photoreceptor to bipolar synapse. It is further proposed that dystrophin isoforms with non-overlapping cellular distributions have distinct roles in retinal function. Three specific aims will be performed to test these hypotheses, involving: (1) defining genotype-phenotype correlations for the DGC performing ERGs on both mutant mice and patients with defects in these proteins; (2) defining the specific cell synapse responsible for the ERG
16 Muscular Dystrophy
abnormalities demonstrated in the mdxCV3 mouse by in vitro cell-specific electrophysiology; and (3) delineating the diversity of dystrophin isoform expression in retina and to determining unique aspects of isoform structure and expression that may contribute to retinal electrophysiology. The long-term goals are to delineate the pathway by which dystrophin contributes to the normal ERG. By so doing, proteins will be identified, which when mutated, will be candidate genes for inherited retinal disorders associated with abnormal electrophysiology. Dystrophin and other proteins including members of the DGC will be targets for future gene therapy approaches. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •
Project Title: CLONING AND CHARACTERIZATION OF GENES EXPRESSED IN SKIN Principal Investigator & Institution: Uitto, Juoni J. Professor and Chair; Thomas Jefferson University Office of Research Administration Philadelphia, PA 191075587 Timing: Fiscal Year 2002; Project Start 01-APR-2002; Project End 31-MAR-2007 Summary: (provided by applicant): The overall goal of this project continues to be the elucidation of gene/protein systems for novel components of the cutaneous basement membrane zone and the epidermis. This goal is based on the premise that previously uncharacterized proteins are apparently present in the skin, and such proteins could potentially serve as candidate gene/protein systems in different heritable disorders affecting the skin. Thus, information on these new proteins and the corresponding genes is fundamental to comprehensive study of mutations in these diseases. During the past four years of support, we have made major progress in this project. Specifically, we have characterized a number of basement membrane zone genes, and the cDNA and gene probes developed in this project have been instrumental in molecular characterization of mutations in various forms of EB as well as in other disorders affecting the epidermis. An example of such gene/protein systems is the plectin/HD-1, for which we have determined the entire primary sequence by cDNA cloning, we have determined the intron-exon organization of the corresponding gene, and we have performed its chromosomal assignment (1). Furthermore, based on this sequence information we have developed mutation detection strategies, both by heteroduplex scanning and protein truncation tests, which have been successful in identifying a large number of mutations in a specific variant of EB associated with late-onset muscular dystrophy (EB-MD) (2-6). Furthermore, we have identified and characterized several novel genes expressed in the epidermis, including ladinin, a novel BMZ component (7), periplakin, an epidermal envelope protein(8,9), and desmo-15, a desmosomal autoantigen in pemphigus herpetiformis recognized by circulating IgG antibodies in the patients? sera (10). Some of these genes were initially isolated by immunoscreening of cDNA libraries with antibodies from patients with acquired autoimmune blistering diseases. Furthermore, we have identified novel protein-protein interactions by the yeast two-hybrid genetic screen employing a number of BMZ protein domains as baits (see Progress Report). Finally, we have cloned a number of selected mouse cDNA and genomic sequences which have been helpful in development of animal models for EB. An example is cloning of the mouse type VII collagen genomic sequences which were used to construct a "knock-out" vector resulting in the development of a mouse line mimicking human recessive dystrophic EB with extensive blistering phenotype (11, 12). In continuation of this project, we will concentrate our efforts towards completing current studies on three novel epidermal gene/protein systems, viz. ladinin, periplakin, and desmo-15. Secondly, we plan to identify additional novel, previously uncharacterized gene sequences by utilizing immunoscreening methodologies with autoantibodies in patients
Studies 17
with acquired forms of blistering skin diseases. Furthermore, we plan to explore the BMZ supramolecular organization by identification and characterization of novel genes which encode interactive proteins, as detected by the yeast-two hybrid genetic screen. Finally, we plan to clone selected mouse cDNA and genomic sequences so as to allow development of animal models for human epidermal diseases. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •
Project Title: CLONING/CHARACTERIZATING A MYOTONIC DYSTROPHY LOCUS Principal Investigator & Institution: Ranum, Laura P. Associate Professor; Neurology; University of Minnesota Twin Cities 200 Oak Street Se Minneapolis, MN 554552070 Timing: Fiscal Year 2001; Project Start 01-JUN-1997; Project End 31-MAY-2005 Summary: Myotonic dystrophy (DM) is a multisystem disease and the most common form of muscular dystrophy in adults. In 1992, one form of DM was shown to be caused by an expanded CTG repeat in the 3' untranslated region of the myotonin protein kinase gene (DMPK) on chromosome 19. Although multiple theories attempt to explain how the CTG expansion causes the broad spectrum of clinical features in DM, there is no consensus about how this mutation, which does not alter the protein coding region of a gene, affects cellular function. We have identified a five-generation family (MN1) with a genetically distinct form of myotonic dystrophy. Affected members have the characteristic features of DM (myotonia, proximal and distal limb weakness, frontal balding, cataracts, and cardiac arrhythmias) but do not have the chromosome 19 mutation. We have mapped the disease locus (DM2) for the MN1 family to a small region of chromosome 3 (Nature Genetics 19:196- 198). This proposal outlines a strategy to identify and characterize the DM2 locus. Understanding what is common to chromosome 19 DM (now designated DM1 by the DM consortium) and DM2 at the molecular level should shed light on the mechanisms responsible for the broad constellation of clinical features present in both diseases. Our specific aims are: 1) to develop a high-resolution map of the DM2 region (0.5-1.0 cM) using haplotype and linkage disequilibrium analysis of 29 DM2/PROMM families from Minnesota and Germany; 2) to identify the expressed genes and repeat motifs in the region and prioritize candidates based on homology and expression patterns; 3) to identify the DM2 mutation; 4) to characterize the DM2 gene and investigate whether or not the pathogenic molecular changes found in DM2 are part of a common pathway also affected in DM1; 5) to determine whether molecular changes affecting RNA splicing, CUG binding proteins, and apamin receptors are similar to those found in DM1. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen
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Project Title: COGNITIVE GENETIC ASPECTS OF DUCHENNE MUSCULAR DYSTROPHY Principal Investigator & Institution: Hinton, Veronica J. Gertrude H Sergievsky Center; Columbia University Health Sciences New York, NY 10032 Timing: Fiscal Year 2003; Project Start 01-MAY-1996; Project End 30-JUN-2007 Summary: (provided by investigator): The objective of this study is to investigate neuropsychological function in individuals diagnosed with Duchenne muscular dystrophy (DMD) as a model for developmental neuroscience. DMD is a single-gene disorder that interferes with the expression of the protein dystrophin and its isoforms. The consequences of lack of dystrophin in muscle are well known; boys have progressive muscular weakness that results in death generally by their third decade of
18 Muscular Dystrophy
life. Dystrophin isoforms are also missing from the central nervous system, yet what functional consequences that may have is unclear. Interdisciplinary study of the cognitive profile, the behavioral attributes, and the molecular genetics of DMD will examine genotype/phenotype associations. The study will build on work that ascertained neuropsychological function in a group of 136 boys diagnosed with DMD and was completed during the tenure of an R29 award. Those data confirmed that boys with DMD who are of average intelligence have selective deficits in verbal working memory with intact declarative memory and visuospatial skills, poor social skills and delayed language developmental milestones. Selected subjects from the established cohort will be examined more thoroughly in focused paradigms to tease apart their language and short-term memory skills using a battery of tests designed to examine the hypothetical "phonological loop." Additionally, subjects will be tested on measures of social function and awareness. New subjects will also be enrolled to increase our sample size for genetic analyses. Subjects with more mild manifestations of the disorder (boys with Becker's muscular dystrophy and carrier females) will be tested on neuropsychological measures to determine whether they present with cognitive phenotypes. An ongoing longitudinal study of a sample of 26 boys will be continued with neuropsychological testing every other year. And newly characterized preschool boys with DMD will be followed to track their language and emotional development. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •
Project Title: COLLOQUIUM ON THE CYTOSKELETON AND HUMAN DISEASE Principal Investigator & Institution: Wilson, Leslie; Professor; Biological Sciences; University of California Santa Barbara 3227 Cheadle Hall Santa Barbara, CA 93106 Timing: Fiscal Year 2001; Project Start 11-APR-2001; Project End 10-APR-2002 Summary: (provided by applicant): A broadly focused international research meeting on the cytoskeleton and its associated proteins in human diseases is planned from April 17 through April 20, 2001. The meeting, entitled Colloquium on the Cytoskeleton and Human Disease, will be held on the medical/pharmacy school campus of the University of the Mediterranean, specifically at the Faculte de Pharmacie, which is located in the center of Marseille. We expect approximately 150 participants including graduate students and post doctoral fellows. It has become clear that the major cytoskeletal components, microtubules, intermediate filaments, and actin filaments, are involved in a large number of diverse human diseases. Thus our purpose is to assemble scientists to participate in the first broadly-based research meeting on the cytoskeleton and its associated proteins in human disease. New drugs and new targets related to the cytoskeleton and its associated proteins will be highlighted. The meeting will consist of invited lectures, short oral communications, and poster sessions. Topics to be covered include: 1)microtubules and cancer (microtubule-targeted anticancer drugs, drug resistance, new approaches and new compounds), 2)microtubule-associated proteins and neurodegenerative disease (Alzheimer's disease and other tauopathies, new concepts and new targets), 3)intermediate filaments and disease (keratin and skin diseases, desmin in skeletal and cardiac muscle disease, muscular dystrophy), and 4)microfilaments and disease ()cell adhesion, migration metastasis, infectious diseases, membrane muscle defects, potential new targets). The members of the organizing committee from the United States are Drs. Leslie Wilson, Mary Ann Jordan, Ernest Braguer, Vincent Peyrot, and Bernard Rossignol. Drs. Wilson, Briand, Jordan, Hamel, Marvaldi, and Binder have the primary responsibility for the scientific program, and Drs. Briand, Wilson, Briand, Wilson, Braguer, Peyrot, and Rossignol are in charge of meeting arrangements.
Studies 19
Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •
Project Title: COMPUTATIONAL ANALYSIS OF HUMAN 'AT-RISK' DNA MOTIFS Principal Investigator & Institution: Stenger, Judith E. Assistant Professor; Medicine; Duke University Durham, NC 27706 Timing: Fiscal Year 2001; Project Start 01-JUN-2001; Project End 31-MAY-2005 Summary: (Taken from the Candidate's Abstract) At-Risk DNA Motifs (ARMS), which include repetitive elements such as Alu sequences, homonucleotide runs and triplet repeats, are potentially unstable segments of the human genome. ARMS are a factor in genetic susceptibility to disease, requiring particular combinations of genetic backgrounds and environmental triggers to express a disease phenotype. While some of the mechanisms are understood, it is not clear under what circumstances repetitive DNA elements mediate pathological mutagenesis. Although a high burden of these sequences is generally tolerated in humans, they can have an enormous impact on health by contributing to diseases that have devastating effects on afflicted individuals. For example, Alus have been linked to numerous diseases including Fanconi anemia, alphazerothalassemia, leukemia, hypertension, neurofibromatosis, breast, and colon cancers. Trinucleotide repeat expansions have been linked with Kennedy's Disease, Huntington's Disease, myotonic muscular dystrophy, and Friedreich ataxia. The long term objective of this proposal is to gain insight into the genetic factors that mitigate gene rearrangement in hopes of predicting when the presence of a repetitive element truly constitutes a threat to the health of an individual. The hypothesis is that the characterization of ARMS according to all possible attributes (i.e. size of repeats, separation distances between repeats, orientation, sequence similarity between repeats, nucleotide base constitution and proximity and/or containment of mutagenic and/or toxicological agent targets, DNA processive or other enzymatic target sites) can reveal largely excluded situations that can be viewed as unstable. It is also postulated that a multidimensional database of repetitive sequences characterized according to the aforementioned attributes can be used to predict repetitive elements that are most prone to mutation, ARMS, while increasing our understanding of the interactions between these genetic elements and their environment. The approach is to use a combination of computational biology and molecular genomic analysis to locate and analyze ARMS. The specific aims of this proposal are to: 1) characterize available data according to the conceivable relevant attributes of size, distance, orientation, degree of homology, base constitution and containment of known target sequences. 2) To test the hypothesis by computationally identifying loci that have already known to contain ARMS linked to a mutation resulting in disease, and then to identify specific genes that may be at-risk for mutation and experimentally testing them using molecular biological approaches. 3) To set up an interactive on-line database and program server so that the scientific community can use the information and apply it to drive experimental research. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen
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Project Title: CONFERENCE--CALPAIN GENE FAMILY IN HEALTH AND DISEASE Principal Investigator & Institution: Mellgren, Ronald L. Professor; Federation of Amer Soc for Exper Bio Bethesda, MD 208143998 Timing: Fiscal Year 2001; Project Start 01-JUN-2001; Project End 31-MAY-2002
20 Muscular Dystrophy
Summary: Support is requested for a FASEB Summer Research Conference on "Calpain Gene Family in Health and Disease" to be held June 30 through July 5, 2001 at The Big Mountain resort in Whitefish, Montana. The calpains are regulated intracellular proteases which participate in a variety of signal transduction pathways, are involved in cytoskeletal remodeling in physiologic and pathophysiologic conditions, and appear to participate in some apoptotic pathways. Several of the calpain family members require the intracellular second messenger Ca2+ for activity. The conference is meant to foster exchange of ideas and collaborations between the many diverse laboratories studying calpains. Participants will include many pioneering calpain researchers as well as young investigators who have recently begun research in this area. Topics will include: 1) Structure/function relationships of the calpains, including likely contributions on calpain crystal structure in the presence of Ca2+, or associated with the natural inhibitor protein, calpastatin. 2) Novel calpain gene family members, biochemical characterization and cellular functions. 3) Mechanisms of regulation of the ubiquitously expressed p- and m-calpains, at the cellular and molecular levels. 4) Physiologic functions of the calpains. 5) Calpains in pathology. Funding is requested to partially support travel expenses and housing for speakers, organizers and promising young investigators. Additional funding will be sought from the Muscular Dystrophy Association, and the USDA, because of calpain involvement in muscular dystrophy and muscle growth. Funding will also be requested from several drug companies which are currently conducting research on calpains. In selecting participants, preference will be given to women and under represented minorities. The speakers include virtually all of the women scientists in the field who have made substantial contributions. Four of the session chairs are women. The Big Mountain resort is a handicapped-accessible facility, and the registration form will question participants about any special needs they may have. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •
Project Title: COORDINATION OF PROCESSING AND TRANSPORT OF MRNA Principal Investigator & Institution: Silver, Pamela A. Professor; Dana-Farber Cancer Institute 44 Binney St Boston, MA 02115 Timing: Fiscal Year 2002; Project Start 01-MAY-1998; Project End 30-APR-2006 Summary: The long-term objective of the proposed research is to understand the mechanism by which mRNAs are exported out of the nucleus. The process of mRNA export includes: proper processing, packaging into protein-RNA complexes, targeting to and movement through the nuclear pore complex and release into the cytoplasm for translation. A transport machinery distinct from that for protein export has been proposed for mRNAs. As with protein import and export, mRNA export can also be regulated by, for example, growth conditions and viral infection. The Specific Aims are to determine how: 1) mRNAs are co- transcriptionally recruited for export; 2) mRNAs are recognized in the nucleus by certain RNA binding proteins; 3) mRNAs are selectively exported under conditions of stress; and 4) protein methylation of RNA binding proteins at arginine affects their activity. Defects in mRNA metabolism that can affect transport are associated with a number of diseases thus contributing to the healthrelatedness of the project. For example, splicing and 3' end formation are associated with a number of diseases including metastatic cancers, muscular dystrophy and amyotrophic lateral sclerosis. In addition, some viruses exploit the endogenous nuclear transport machinery in order to propagate - in some cases by inhibiting export of host in favor of viral messages. Methylation of RNA and DNA binding proteins at arginine has recently emerged as important for many levels of regulation including viral RNA
Studies 21
export, response of cells to interferon and the action of certain RNA binding proteins in motor neuron degeneration in spinal muscular atrophy. Lastly, arginine-methylated proteins such as hnRNPs and myelin basic protein are prominent in autoimmune diseases such as systemic lupus erythematosus and multiple sclerosis. It may be that modified arginine elicits special recognition properties that lead to exacerbation of autoimmune diseases. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •
Project Title: CORE--ANIMAL MODELS AND IMMUNOLOGY LAB Principal Investigator & Institution: Bromberg, Jonathan S. Surgical Director; University of Michigan at Ann Arbor 3003 South State, Room 1040 Ann Arbor, MI 481091274 Timing: Fiscal Year 2001 Summary: The central purpose of the Animal Models Core is to provide the affiliated investigators with the appropriate genotype and strain of rodent for the proposed studies, and to provide a range of immunological assays on animals inject with adenoviral vectors. The Animal Models Core is specifically dedicated to investigations of novel strategies of gene delivery to aged or dystrophic striated muscle, as well as mechanistic based evaluations of the effects of genetic modification of dystrophin on muscle cell mechanical properties in young and aged animals. All rodents will be raised and maintained under specific-pathogen-free conditions at the University of Michigan AAALAC-accredited animal facility. In addition to maintaining stocks of animals for testing, the core will conduct a detailed life span analysis of the dystrophic mdx mouse. This core lab will also handle all the immunology required for analysis of adenoviral vector development. A goal of our new vector design is to develop an adenoviral based vector that does not trigger a strong immune response in host animals, particularly a cytotoxic T-cell mediated response. Animals that are injected with virus will be used not only to assess the longevity and functional consequences of gene expression, but will also be tested for potential immune responses against the virus and the transgene being delivered. This analysis will involve CTL-assays against adenoviral and transgene proteins, as well as B cell mediated humoral immune responses against the same proteins. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen
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Project Title: CORE--CLINICAL SPECIMEN AND DATA Principal Investigator & Institution: Engle, Elizabeth C. Associate Professor of Neurology; Children's Hospital (Boston) Boston, MA 021155737 Timing: Fiscal Year 2001; Project Start 25-SEP-2001; Project End 31-AUG-2006 Summary: (provided by applicant): The four projects in this Program Project share the common theme of characterizing and understanding normal and abnormal patterns of gene expression in developing muscle from the stem cell stage through to maturity. The Program PI?s have a long and extensive history of interaction and have exchanged ideas, biopsy samples, and other reagents over many years. This Program Project is designed to further strengthen these collaborations and to produce synergistic results that are beyond the scope of any one laboratory. The services of the Clinical Specimen and Data Core (Core B) will be one important means by which the Program Project will meet these goals. The techniques required to perform the Aims of this Core are standard within the laboratories of each PI. By centralizing these techniques, formalizing data and tissue collections, and developing a database within the Muscular Dystrophy Research Portal (MDRP), Core B will increase efficiency and provide standardization to the
22 Muscular Dystrophy
analysis of data for each Project and the Program overall. Toward this end, the Aims of Core B are designed to maximize efficiency and minimize both administrative and technical effort and expense. Aim 1. Ascertain the Program Project patient and control participants and acquire the comprehensive clinical data, peripheral blood samples, and muscle tissue samples from both patients and controls (Projects served: 1, 2, 3, 4, Core C). Aim 2. Catalogue and track all clinical (Aim 1) and diagnostic data (Aims 1 and 4) pertaining to patients and blood/tissue samples. Annotate and enter all data into the muscular dystrophy research portal (MDRP) (Projects served: 1, 2, 3, 4, Core C). Aim 3. Prepare muscle tissue samples for gene expression analysis. Isolate mRNA and synthesize labeled cDNA/cRNA for hybridization to Affymetrix oligonucleotide and Genetic Microsystems cDNA arrays (Projects served: 1, 2, 3, Core C). Aim 4. Isolate DNA from patient blood samples and provide selective verification of participant's disease mutations (Projects served: 1, 2, 3). Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •
Project Title: CORE--CONTRACTILITY Principal Investigator & Institution: Faulkner, John A. Professor; University of Michigan at Ann Arbor 3003 South State, Room 1040 Ann Arbor, MI 481091274 Timing: Fiscal Year 2001; Project Start 15-JUL-2001; Project End 30-APR-2002 Summary: The purpose of the Contractility Core is to provide collaborating investigators in the Program Project with reliable and valid measures of the contractile properties of whole striated muscles and of strips of diaphragm muscle fibers, statistical analysis of the data, and interpretation of the structure-function relationships. The Core will also provide opportunities for instruction and training for faculty and trainees who wish to learn the techniques. Muscle fibers when activated attempt to contract or shorten. Whether an activated myofiber shortens, stays at the same length or is stretched depends on the interaction between the force developed and the load. For striated muscle, contractility is defined as the capability of muscle fibers to develop force during fixed length or isometric contractions, during shortening or miometric contractions, and during lengthening or pliometric contractions. Our working hypothesis is that contractility of striated muscles is a complex phenomenon and the provision of reliable and valid measurements requires sophisticated equipment and highly trained muscle mechanicists to make the measurements and analyze and interpret the results. Consequently, to test hypothesis relating the underlying mechanisms of the reduced contractility of striated muscles in diseased and old animals rigorously, a Contractility Core is a necessity. Impairments during each of the three types of contraction may occur at any age due to injury or disease or as an intractable concomitant of aging. The impairments in contractility, whether due to injury, disease, or old age, limit the activities of daily living and reduce the quality of life, particularly for the sick and the elderly. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen
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Project Title: CORE--FAMILY ASCERTAINMENT, LINKAGE ANALYSIS AND INFORMATICS Principal Investigator & Institution: Pericak-Vance, Margaret A. Professor; Duke University Durham, NC 27706 Timing: Fiscal Year 2001 Summary: The Family Ascertainment, Linkage Analysis, and Informatics Core provides a comprehensive framework for clinical and statistical resources necessary to identify
Studies 23
genes which predispose to human disease. These functions are highly interdependent and critical to the success of linkage studies. Central to both the family ascertainment and statistical components is the PEDIGENE database. PEDIGENE is a relational database that integrates family history, clinical, and genotypic marker results together with DNA banking and genomics that integrates family history, clinical, and genotypic marker results together with DNA banking and genomics functions from Core B. This flexible, highly secure genetic database system continues to be instrumental in the rapid and accurate assimilation of and access to all types of genetic data. This core will serve as the umbrella for coordinating and performing all linkage studies in projects 1 and 3, from initial linkage through characterization of heterogeneity through fine mapping, in Mendelial diseases. These diseases include Charcot-Marie- Tooth disease type 2, familial spastic paraparesis, the autosomal dominant limb-girdle muscular dystrophies, facioscapulohumeral muscular dystrophy, and the Lumbee myopathy. The Core also provides consulting support for complex trait analysis such as in project 2, including non-parametric linkage analysis (siblink) and TDT. In addition, this core provides seed support for several projects under development including studies of neural tube defects and Chiari type 1 malformation. Ultimately, these projects will be developed to a point to ensure independent funding, thereby maximizing the impact of the availability of these critical core resources. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •
Project Title: CORE--MUSCLE PHYSIOLOGY Principal Investigator & Institution: Watchko, Jon F.; University of Pittsburgh at Pittsburgh 350 Thackeray Hall Pittsburgh, PA 15260 Timing: Fiscal Year 2001 Summary: The Muscle Physiology Core is a well equipped in vitro physiology laboratory staffed with experienced personnel skilled in executing personnel skilled in executing the proposed contractile studies. This Core will be supervised by Jon Watchko, M.D., and be available to all principal investigators assisting them in achieving their research goals evaluating the effects of gene therapy on skeletal muscle function. In addition to meeting the overlapping needs of individual projects and thereby being the most efficient use of space, equipment and personnel talent, this Core will enhance collaboration between investigators. The Specific Aims of the Muscle Physiology ore are to i) obtain natural history data on muscle function of the tibialis anterior in normal and dystrophic (dystrophin-deficient mdx) mice, and normal and dystrophic cardiomyopathic) hamsters, and ii) determine the positive or negative effects of viral vector gene delivery on contractile function of the tibialis anterior muscle of dystrophin deficient mice and delta- sarcoglycan hamsters. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen
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Project Title: CRYSTALLOGRAPHIC POLY(A)POLYMERASE
STUDIES
OF
EUKARYOTIC
Principal Investigator & Institution: Doublie, Sylvie; Microbiol & Molecular Genetics; University of Vermont & St Agric College 340 Waterman Building Burlington, VT 05405 Timing: Fiscal Year 2001; Project Start 18-DEC-2000; Project End 30-NOV-2005 Summary: (From the applicant's abstract) The long-term goal of this project is to understand the molecular mechanisms of eukaryotic mRNA polyadenylation. mRNA polyadenylation plays an essential role in the initiation step of protein synthesis, in the export of mRNAs from the nucleus to the cytoplasm, and in the control of mRNA
24 Muscular Dystrophy
stability. Polyadenylation is a key regulatory step in the expression of many genes. Aberrant polyadenylation has been shown to cause diseases such as thalassemia and lysosomal storage disorder. Moreover, oculopharyngeal muscular dystrophy is the result of the insertion of short GCG repeats in the gene encoding one of the polyadenylation factors, poly(A) binding protein 2 (PABP 2). We are investigating the crystal structure of the enzyme at the heart of the polyadenylation machinery, poly(A) polymerase (PAP), its interaction with substrates, and its association with proteins playing a part in mRNA 3'-end processing. There are no structural data to date for any of the mammalian polyadenylation factors. The specific aims are as follows: 1. The X-ray crystal structure of bovine PAP with its substrates ATP and poly(A) RNA will be determined using a combination of multiwavelength anomalous diffraction (MAD) and multiple isomorphous replacement. The structure of PAP complexed with substrates will guide additional structural and functional studies. 2. PABP 2 is required for processive synthesis and control of the poly(A) tail length. PABP2 is known to bind both the poly(A) tail and PAP. We will work towards the structure determination of the ternary complex of PABP2, PAP, and poly(A), using either the intact proteins or the interacting domains of each protein. 3. Phosphorylation of target sites located in the Cterminal domain of PAP results in strong repression of PAP activity. The down regulation of PAP via hyperphosphorylation is reminiscent of the inhibitory effect of U1A, which has been shown to inhibit polyadenylation of its own mRNA by binding to PAP. We will work towards the crystallization of the complex between PAP and U1A, using either the intact proteins, or the C-termini of each protein. We will concurrently attempt to crystallize phosphorylated, full-length bovine PAP. A comparison of the phosphorylated PAP structure with that of the PAP-U1A complex should elucidate whether both situations use a similar mechanism of repression. It is expected that these results will not only provide a sound structural basis for understanding the mechanism of polyadenylation at the molecular level but will also shed light on the mechanisms of processivity and repression. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •
Project Title: CYTOKINESIS AND CELL POLARITY IN C ELEGANS EMBRYOS Principal Investigator & Institution: Bowerman, Bruce A. Associate Professor; None; University of Oregon Eugene, OR 97403 Timing: Fiscal Year 2001; Project Start 01-MAY-1999; Project End 30-APR-2003 Summary: We propose to use the powerful genetics and the impressive cytological properties of the early C. elegans embryo to investigate cytokinesis and its relationship to mitotic spindle orientation in a developing animal. The early C. elegans embryo offers two key advantages for these studies: (i) the ability to rapidly identify genes required for cytokinesis and for mitotic spindle orientation in early embryonic cells, and (ii) the ability to visualize with high resolution the subcellular localization of functionally important proteins in the large (approximately 22 x 55 micron) 1-cell stage zygote. We have three long term goals: (1) To use genetic and molecular methods to define cytokinesis as a series of discrete molecular interactions that execute cytokinesis in the early embryo. (2) To determine the mechanistic relationship between the termination of cytokinesis and the mechanisms that orient mitotic spindles during asymmetric divisions in early embryonic cells. (3) To identify motor proteins important for cytokinesis and the generation of asymmetric cell divisions. These studies will provide significant insight into the molecular basis for human pathologies: cytoskeleton/plasma membrane interactions have proven relevant to our understanding of cancer and of other significant diseases, including muscular dystrophy, deafness, and sterility. In
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preliminary studies, we have identified a gene called cyk-1 that is required for a late step in cytokinesis. This is the first gene identified in C. elegans that is specifically required for cytokinesis in the early embryo. Intriguingly, the CYK-1 protein localizes to the leading edge of the cleavage furrow late in cytokinesis, where we hypothesize it bridges the actin and tubulin cytoskeleton. While CYK-1 provides a starting point for identifying functionally protein/protein interactions that occur during cytokinesis, we first propose to identify as comprehensively as possible the genes required for cytokinesis and mitotic spindle orientation. To this end, we have begun a large-scale screen for temperature-sensitive, embryonic-lethal mutants, and we are using a functional genomics approach that involves the use of a recently discovered technology called RNA interference. We will molecularly clone genes that are most specifically required for cytokinesis and mitotic spindle orientation. By using genetic and molecular epistasis experiments, and by examining how the different proteins we identify interact, we will define the molecular interactions and pathways that control these fundamental cellular and developmental processes. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •
Project Title: CYTOSKELETAL INTERACTIONS OF DYSTROPHIN Principal Investigator & Institution: Ervasti, James M. Professor; Physiology; University of Wisconsin Madison 750 University Ave Madison, WI 53706 Timing: Fiscal Year 2001; Project Start 15-JUL-1994; Project End 31-MAR-2005 Summary: (Verbatim from the Applicant's Abstract): The objective of this project is to determine the cytoskeletal interactions of the dystrophin-glycoprotein complex in the skeletal muscle to understand how its absence or abnormality leads to Duchenne (DMD) and Becker (BMD) muscular dystrophies and some forms of cardiomyopathy. Rather than just simply serving to anchor its associated glycoprotein complex to the cortical actin, our previous studies lead us to hypothesize that dystrophin also plays an important role in stabilizing the cortical cytoskeleton through an extended lateral association with actin filaments. We further hypothesize that the dystrophin homologue utrophin is missing an actin binding suite important for F-actin stabilization. These hypotheses will be tested, both in vitro and in vivo, through the pursuit of 3 complementary specific aims. The F-actin binding properties of full-length and truncated forms of recombinant dystrophin and utrophin will be measured by established biochemical and spectroscopic procedures (Aim 1). Completion of this aim will yield the first direct structure/function comparison for dystrophin and utrophin up-regulation to effectively compensate for dystrophin deficiency. Recombinant dystrophin/utrophin will be visualized alone and in complex with actin filaments using electron microscopy combined with three-dimensional reconstruction techniques (Aim 2). These studies will yield important new information about the shape, dimensions and flexibility of dystrophin and utrophin and will independently determine how much (and which sub-domains) of dystrophin lie in close apposition with F-actin. Analysis by three-dimensional reconstruction will also identify changes in actin monomer and filament structure that may lead to more stable association of other costameric proteins with F-actin. Finally, we will relate the in vitro features of the dystrophin/F-actin interaction with its role in stabilizing costomeric actin in vivo (Aim 3). Sarcolemmal membranes will be mechanically isolated from muscles of transgenic mdx mice expressing dystrophin constructs deleted in different domains and the status of costameric actin determined by confocal microscopy. We will also determine whether the absence of dystrophin results in an unstable sarcolemmal association of other costameric actin binding proteins. Completion of these aims will result in a highly
26 Muscular Dystrophy
detailed and integrated understanding of dystrophin's role in stabilizing the muscle membrane cytoskeleton through its interaction with cortical actin. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •
Project Title: PATHWAY
CYTOSOL/VESICLE/VACUOLAR
PROTEIN
DEGRADATION
Principal Investigator & Institution: Chiang, Hui-Ling; Cellular/Molecular Physiology; Pennsylvania State Univ Hershey Med Ctr 500 University Dr Hershey, PA 17033 Timing: Fiscal Year 2001; Project Start 01-SEP-1998; Project End 31-AUG-2002 Summary: Protein degradation is important for cell cycle control, signal transduction and cell growth. Abnormal protein degradation has been implicated in metabolic disorders, cancer development and muscular dystrophy. A novel pathway of protein degradation in the yeast vacuole has been established in our lab. They key gluconeogenic enzyme, fructose-1.6- biophosphatase (FBPase), is targeted from the cytosol to the yeast lysosome (vacuole) for degradation when Saccharomyces cerevisiae are replenished with glucose. Our long term goal is to understand the FBPase degradation pathway. We have reconstituted this glucose-regulated targeting pathway using semi-intact cells, purified FBPase, an ATP regenerating system and cytosol. FBPase is targeted to the vacuole in the reconstituted system. We have isolated 33 vid (vacuolar import and degradation) mutants defective in the glucose-induced degradation of FBPase. Mutant analysis led to the hypothesis that FBPase is targeted from the cytosol to the intermediate vesicle and then the vacuole for degradation. We have purified a novel FBPase-associated vesicle to near homogeneity. We cloned the VID24 gene involved in vesicle targeting to the vacuole. Vid24p is synthesized and localized to the vesicles. Our specific aims are: (1) Reconstitution of FBPase import into the vesicle using the vid24-1 mutant. We will examine whether the imported FTPase is indeed targeted to the intermediate vesicles. We will divide vid1-vid13 which accumulates FBPase in the cytosol into functional subgroups. (2) Cloning of the VID genes. We plan to clone the VID genes using the colony blotting procedure and study the expression and localization of the Vid proteins. As an alternative approach, we will clone the VID15 gene which is tightly linked to the URA3 gene by chromosomal walking. (3) Purification of cytosolic proteins required for FBPase import into the vesicles. We will use the vid1-vid13 mutants that contain defective cytosolic factor(s) and add fractionated wild type cytosol to identify the fractions that complement the mutant cytosol defect. If we identify such protein, we will make mutants and prepare cytosol from the mutants to test whether the cytosol is defective in FBPase import in vitro. We will examine whether FBPase import into the vesicles is regulated by ATP or GTP hydrolysis. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •
Project Title: DB TRIAL OF PROVENTIL IN FACIOSCAPULOHUMERAL MUSCULAR DYSTROPHY Principal Investigator & Institution: Kissel, John; Ohio State University 1800 Cannon Dr, Rm 1210 Columbus, OH 43210 Timing: Fiscal Year 2001 Summary: This abstract is not available. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen
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Project Title: DETERMINANTS OF MYOGENIC AND NEURONAL MEMBRANE PHENOMENA Principal Investigator & Institution: Horwitz, Alan F. Professor and Head; Cell Biology; University of Virginia Charlottesville Box 400195 Charlottesville, VA 22904 Timing: Fiscal Year 2001; Project Start 01-JAN-1988; Project End 31-DEC-2002 Summary: Skeletal muscle is an ideal system with which to study adhesion molecules and the membrane-cytoskeletal linkages in which they participate as they play a central role in muscle development, structure and physiology, and pathology. Once muscle precursors have migrated to their targets, the program of terminal differentiation commences, which is regulated by the extracellular matrix. An elaborate contractile apparatus is synthesized and organized, which contains several cell surface associations including the myotendinous and costomeric junctions. Muscle cells are innervated at neuromuscular junctions. It is now clear that dystrophin, the muscular dystrophy gene product, has homologies to cytoskeletal proteins and is associated with adhesion molecules like integrin. The integrin family of receptors for extracellular matrix molecules are implicated in all of the above phenomena by virtue of their localization in junctional regions, their functions as dual receptors for extracellular matrix and cytoskeletal molecules, and as mediators of signal transductions. The hypothesis that guides our current research is that the integrins play a central role in organizing the surface, the extracellular matrix, and the contractile apparatus of skeletal muscle and in addition mediate signals from the extracellular matrix triggering its differentiation. Our general aims for the project period are to identify and characterize the amino acid sequences on integrin cytoplasmic and extracellular domains that determine the organization of junctional regions and determine their role in adhesion. This will be done using a recently constructed library of single-amino acid substitutions in the Beta1cytoplasmic domain and synthetic peptides corresponding to active and mutant sequences. A similar library will be constructed for alpha subunits. Analogous, but different, methods are proposed to find extracellular matrix binding sequences in the extracellular domain. The second major aim is to identify and purify novel integrin associated cytoplasmic proteins. Previous specificity problems will be addressed using peptide sequences derived from mutant and wild type cytoplasmic domain sequences. Recently we have identified two novel integrin associated molecules. Both are cytoskeletal and one is a complex of 5 proteins. They will be characterized further for binding specificities and localization on muscle. The third objective is to elucidate the role of integrins in organizing and stabilizing junctional regions. This will be done using molecular genetic techniques to identify functional domains, alter regulation of expression, and reduce or eliminate the expression of specific integrins. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen
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Project Title: DISINTEGRINS & METALLOPROTEINASES IN ORTHOPEDIC DISEASE Principal Investigator & Institution: Smith, Jeffrey W.; Burnham Institute 10901 N Torrey Pines Rd San Diego, CA 92037 Timing: Fiscal Year 2001; Project Start 01-APR-1994; Project End 31-MAR-2003 Summary: (Adapted from the Applicant's Abstract): The events leading to cell-cell fusion are key to the development and homeostasis of bone and muscle. The broad objective of this study is to understand the mechanisms that lead to the differentiation and fusion of osteoclasts and myotubes. Results from the study could lead to new treatments for osteoporosis and muscular dystrophy. The hypothesis of the proposal is
28 Muscular Dystrophy
that a recently discovered family of transmembrane proteins, called ADAMs, are important in the differentiation of bone and muscle. The ADAMS contain A Disintegrin And Metalloproteinase domain. The study will initially focus on meltrin-alpha, an ADAM expressed by myoblasts and osteoclasts. One objective of the study is to perform the first characterization of the biosynthesis and cellular localization of meltrin-alpha. These experiments will determine if the metalloproteinase domain of meltrin is released from the cell surface, and whether meltrin-alpha co-localizes with integrin in focal adhesion sites. A second objective will be to determine how each domain of meltrinalpha is involved in the fusion of myoblasts. In this analysis, site-directed mutagenesis and polyclonal antibodies will be applied to ablate the biochemical activity of domains of meltrin, and the effects of these manipulations on myogenesis will be assessed. A third objective is to examine the structure-function relationships of the metalloproteinase and disintegrin domains of meltrin-alpha. Phage-display will be used to build inhibitors of the metalloproteinase. Studies will be conducted to identify the cell surface receptor for the disintegrin domain of meltrin-alpha. A final objective is to identify the ADAM proteins present in osteoclasts and their precursors. Homologybased PCR will be used to clone osteoclast ADAMs. Antibodies against these ADAMs will be used in attempts to block osteoclast differentiation. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •
Project Title: DISULFIDE STRUCTURE OF BIOMEDICALLY IMPORTANT PROTEINS Principal Investigator & Institution: Watson, Jack T. Associate Professor; Biochemistry; Michigan State University 301 Administration Bldg East Lansing, MI 48824 Timing: Fiscal Year 2001; Project Start 01-FEB-2001; Project End 31-JAN-2005 Summary: Disulfide bonds are a critically important determinant of the shape and, thus, the activity of some biomedically important proteins. The common bleeding disorder, von Willebrand Disease, appears to be related to a defect in the disulfide bonding pattern among 18 cysteines (including two pairs of adjacent cysteines) of a particular protein (VWF) that disrupts the normal blood clotting cascade. Very little is known about the cysteine status of the von Willebrand protein (VWF), and such knowledge will help explain the cause of this disorder at the molecular level; however, VWF is resistant to the conventional proteolytic approach to disulfide mapping. Knowledge of the disulfide bonding pattern in the receptor- binding proteins for TGF-beta will help provide an important 'template' for the development of drugs (antagonists) for treatment of fibrotic disorders ,e.g., Duchennes muscular dystrophy; similarly, the development of other drugs (agonists) may serve as anti-cancer agents by promoting the negative proliferative response to TGF-beta. However, the highly knotted, cysteine-rich (up to 12 cysteines, 3 of which are adjacent) receptor-binding proteins for TGF-beta are resistant to conventional disulfide mapping. Developing a protocol for the disulfide mapping of VEGF homodimer will provide the basis for designing and monitoring the proper folding of related pharmaceutical proteins with angiogenic activity. Our novel approach to disulfide mapping, based on cyanylation of and cleavage at cysteine residues, offers new hope for determining the disulfide bonding pattern of the biomedically important cystinyl proteins described above that are refractory to conventional methodology. Cyanylation is selective for free sulfhydryls and can be accomplished at pH 3, a condition that suppresses problems with disulfide scrambling. We have demonstrated that the cyanylation/cleavage approach is applicable to proteins containing adjacent cysteines, an attribute that recommends it for successfully attacking the difficult analytical challenges posed by the proteins described herein. An a1gorithm
Studies 29
will be developed to assign the connectivity of cysteines in disulfide bonds given an input of amino acid sequence and mass spectra of cyanylation/cleavage products. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •
Project Title: DMD GENE THERAPY USING HSV/AAV HYBRID VECTOR SYSTEM Principal Investigator & Institution: Wang, Yaming; Brigham and Women's Hospital 75 Francis Street Boston, MA 02115 Timing: Fiscal Year 2001; Project Start 15-AUG-2000; Project End 31-JUL-2003 Summary: The principle investigator for this proposal, Dr. Yaming Wang, is an Instructor in Anesthesia at Brigham and Women's Hospital and Harvard Medical School. The work outlined in this proposal will serve to fund the mentored transition of Dr. Wang into gene therapy of muscular diseases and from a research associate to an independent academic investigator and application R01 level funding. The mentor in this proposal, Dr. Allen is an independent clinical scientist with extensive published experience in the area of muscle biology. A mentor committee consisting of Dr. Allen and three other scientists (Dr. Breakefield, Dr. Kunkle, and Dr. Leboulch) will serve as the advisory committee for Dr. Wang and will carefully oversee her progress. The environment in which the proposed work will be carried out (Harvard Medical School) is a world class scientific community where biomedical research is performed at the highest level with intimate associations between clinical and basic science disciplines. In this proposal, Dr. Wang will investigate the effectiveness of an exciting novel hybrid HSV/AAV amplicon virion expressing dystrophin as a possible solution to the problems facing the currently proposed and active gene therapy protocols for a common X-linked myopathy, Duchenne's Muscular Dystrophy (DMD). Current therapy has failed because it has been unsuccessful in obtaining durable expression of the transferred gene product. There were a number of reasons for this failure, such as cytotoxicity, immune reactions caused by with viral gene expression and virion proteins, and non-integration of vector DNA. She has demonstrated that the HSV-1 amplicon virions are capable of transducing skeletal muscle myofibers in vivo and myoblasts and myotubes in vitro using both GFP and dystrophin as the experimental marker gene. Both GFP and dystrophin virions were shown to permanently transduce myoblasts in culture at a low frequency (0.5-2 percent) suggesting their ability to integrate into the host genome. As a work in progress she has designed new amplicon vectors capable of carrying the 14kB dystrophin cDNA, GFP and an antibiotic selection marker, and has demonstrated that these amplicons can be packaged into HSV virion particles that can induce transcription of the appropriate protein in mdx myotubes. The overall aim of this project is to create a new nontoxic, high efficiency and long term transgene expression AAV/HSV-1 hybrid vector system to express dystrophin in a mdx mouse animal model to attempt DMD phenotype correction. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen
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Project Title: DUAL AAV VECTORS FOR DUCHENNE MUSCULAR DYSTROPHY THERAPY Principal Investigator & Institution: Duan, Dongsheng; Assistant Prof. of Microbio & Immunology; Molecular Microbiol and Immun; University of Missouri Columbia 310 Jesse Hall Columbia, MO 65211 Timing: Fiscal Year 2003; Project Start 14-JUL-2003; Project End 30-APR-2008 Summary: (provided by applicant): Duchenne muscular dystrophy (DMD) is the most common form of inherited muscle disease. It usually leads to death from respiratory or
30 Muscular Dystrophy
cardiac failure by age 20. Currently, no effective treatment is available for this fatal disease. DMD is an X-linked genetic disease caused by dystrophin gene mutation. Gene therapy represents a very promising avenue to cure DMD. Recombinant adenoassociated virus (rAAV) mediates high-level persistent transgene expression in muscle. Recent clinical trials have further confirmed the efficiency and the safety of rAAV vectors in muscle. However, rAAVmediated DMD gene therapy has been significantly limited by the small viral packaging capacity. Only the highly truncated C-terminaldeleted versions of "micro-dystrophin" genes have been attempted. Both clinical and transgenic studies show that the C-terminal-inclusive larger genes (such as the 6.0-6.3kb "mini-dystrophin" genes and the approximately 4.7kb "C-terminal-inclusive microdystrophin" genes) are therapeutically superior. Unfortunately the strong therapeutic expression cassettes derived from these genes are too large to be packaged in a single AAV virion. We have recently developed several dual vector approaches to expand AAV packaging capacity. Among these, the concatamerization-based "trans-splicing" and "cis-activation" strategies hold great promise for delivering the C-terminal-inclusive larger dystrophin genes. However, the expression level achieved so far is not sufficient for DMD gene therapy. In this proposal, we plan to extend our previous findings and further explore the molecular mechanisms underlying these methods, in the hope of improving the transduction efficiency for DMD gene therapy. In particular, we will try to identify and overcome the rate-limiting barriers to transgene expression. These include problems associated with dual vector co-infection, concatamerization of AAV genome inside cell, and transcription, splicing, and stability of AAV concatamers. More important, we will apply this newly obtained information to generate the most effective trans-splicing and cis-activation AAV vectors for the C-terminal-inclusive larger dystrophin genes. Therapeutic potentials of these newly developed AAV vectors will be rigorously tested in the limb muscle, diaphragm, and heart of the murine DMD model (mdx mouse). A comprehensive array of assays will be used to examine the level of gene expression and the functional improvement in muscle histology and contraction. To address safety concerns, we also plan to evaluate the potential deleterious effects from putative truncated protein production in the trans-splicing method. Taken together, our findings will lead to the eventual application of these very promising dual AAV vector strategies to the human DMD gene therapy. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •
Project Title: DYSTROPHIN REPLACEMENT IN MDX MICE Principal Investigator & Institution: Chamberlain, Jeffrey S. Professor; Neurology; University of Washington Seattle, WA 98195 Timing: Fiscal Year 2001; Project Start 01-APR-1991; Project End 31-MAR-2005 Summary: (Adapted from applicant's abstract): Duchenne muscular dystrophy (DMD) is an X-linked recessive, lethal disorder caused by mutations in the dystrophin gene. Considerable progress has been made both in understanding the function of dystrophin, and in demonstrating the feasibility of gene therapy for DMD. Nonetheless, numerous obstacles remain before gene therapy can be effectively applied to this common genetic disease. These obstacles include a lack of data on the reversibility of the dystrophic pathology, limited ability of viral vectors to carry the enormous dystrophin gene or cDNA, and questions about the effectiveness of inefficient delivery methods of dystrophin vectors. This application proposes to address these concerns by generating several novel strains of transgenic mice. The ability to modulate the dystrophic phenotype will also be explored using viral delivery of dystrophin and several death protectors to mdx mice, a model for DMD. Transgenic mice that express moderate levels
Studies 31
of dystrophin are able to prevent the development of dystrophy in the mdx mouse, a model for DMD. Delivery of adenoviral vectors expressing truncated dystrophins to neonatal, immune tolerant mice can also prevent muscular dystrophy near the site of injection. However, it has not been possible to demonstrate that the pathology can be halted or reversed in adult, dystrophic animals. Aim1 will address the feasibility of reversing muscular dystrophy at different stages of the disease by studying a transgenic mouse line that displays tetracycline-inducible dystrophin expression. Aim 2 will continue previous work aimed at understanding the structural basis of dystrophin functional domains, with the goal of developing severely truncated cDNAs that can be carried by a variety of promising viral vectors, such as adenoassociated viruses (AAV). Currently, the only vectors capable of carrying the full-length dystropin cDNA have problems with cytotoxicity, immune rejection or low titers. AAV efficiently infect muscle with no immune response, but have a limited cloning capacity. Aim 3 explores the ability to modulate dysrtophy by delivery of dystrophin with proteins that repress apoptosis and/or enhance muscle regeneration. Achieving uniform and efficient gene delivery to muscles using viral vectors is a daunting goal. The ability to modulate dystrophy and prolong muscle fiber longevity could greatly facilitate the effectiveness of dystrophin gene replacement strategies. These studies will provide new insights into both the structure of dystrophin and the mechanisms of dystrophic cell death and will help advance the development of gene therapy. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •
Project Title: DYSTROPHIN-GLYCOPROTEIN COMPLEX IN CARDIOMYOPATHY Principal Investigator & Institution: Michele, Daniel E. Physiology and Biophysics; University of Iowa Iowa City, IA 52242 Timing: Fiscal Year 2003; Project Start 01-MAY-2003; Project End 31-AUG-2005 Summary: (provided by applicant): The long term objective of this proposal is to understand the molecular basis of inherited cardiomyopathies, particular those associated with mutations in components of the dystroglycan-glycoprotein complex. The dystroglycan-glycoprotein complex provides a link from the cytoskeleton to the extracellular matrix. Mutations in components of this complex, such as delta sarcoglycan, cause recessive forms of muscular dystrophy. Interestingly, heterozygous mutations in the same delta sarcoglycan can also cause dilated cardiomyopathy without muscular dystrophy. The basis for the tissue specificity of these mutations and the mechanism behind sarcoglycan associated dilated cardiomyopathy is unclear. Furthermore, muscular dystrophy patients with mutations in enzymes that glycosylate dystroglycan and whose activity is necessary for dystroglycan to bind extracellular ligands, also have a high prevalence of cardiomyopathy. This proposal tests the hypothesis that the link between the cytoskeleton and the extracellular matrix 'through dystroglycan, specifically in cardiac myocytes, is critical 'to the development of cardiomyopathy. The proposed research will test the dominant-negative and tissue specific effects of delta sarcoglycan mutations on the attachment of alpha-dystroglycan to the transmembrane complex using isolated muscle cell gene transfer. In addition, the tissue specific role of dystroglycan glycosylation in the link to the extracellular matrix and the development of cardiomyopathy will be tested in the myodystrophy mouse. Finally, tissue specific gene targeted mice will be generated to determine if the link from cytoskeleton to matrix through dystroglycan, is necessary and sufficient in a tissue specific manner, to cause and explain the development of DGC associated cardiomyopathy. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen
32 Muscular Dystrophy
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Project Title: DYSTROPHIN-GLYOPROTEIN CARDIOMYOPATHY
COMPLEX
AND
DILATED
Principal Investigator & Institution: Knowlton, Kirk U. Associate Professor; University of California San Diego 9500 Gilman Dr, Dept. 0934 La Jolla, CA 92093 Timing: Fiscal Year 2001 Summary: Dilated cardiomyopathy is a multi-factorial disease that includes both the hereditary and acquired forms of cardiomyopathy. Recent experiments have shown that hereditary cardiomyopathy in humans can be associated with genetic defects in components of the dystrophin-glycoprotein complex. For example, mutations in the dystrophin gene lead to a high incidence of cardiomyopathy in Duchenne and Becker muscular dystrophy, and can caused X-linked dilated cardiomyopathy. Mutations in the genes for the sarcoglycans are responsible for limb girdle muscular dystrophy and are often quite associated with cardiomyopathy. In addition, our preliminary data links an acquired form of cardiomyopathy, enteroviral infection, with disruption of the dystrophin-glycoprotein complex. Thus, evidence is accumulating that the dystrophinglycoprotein complex has a critical role in the genesis of hereditary and acquired cardiomyopathy. Dystroglycan is a key component of the dystrophin- glycoprotein complex that links the cytoskeletal protein dystrophin to the extracellular matrix protein laminin-2. Recent experiments with dystroglycan null ES cells have demonstrated that dystroglycan is required for basement membrane assembly but not cardiac myocyte differentiation. Sarcoglycans interact closely with dystroglycan and recent studies of sarcoglycan null mice have suggested that the underlying mechanism of sarcoglycan related cardiomyopathy is due to the dysfunction of vascular smooth muscle. The overall goal of this project is to test the hypothesis that the dysfunction of the dystrophin-glycoprotein complex can lead to dilated to dilated cardiomyopathy. We plan to test the following three hypotheses: 1) disruption of dystroglycan in the cardiac myocyte is sufficient to disrupt normal basement membrane assembly and induce cardiomyopathy; 2) disruption of sarcoglycan function in the vascular smooth muscle is sufficient and necessary to induce the cardiomyopathy that occurs with genetic alteration of the vascular smooth muscle is sufficient and necessary to induce the cardiomyopathy; 2) disruption of sarcoglycan function in the vascular smooth muscle is sufficient and necessary to induce the cardiomyopathy that occurs with genetic alteration of the sarcoglycan complex; and 3) cleavage of dystrophin in the cardiac myocyte contributes significantly to to the cardiomyopathy of enteroviral infection. To directly examine dystroglycan's function in the heart we have proposed experiments in the first specific aim to circumvent the early lethality of dystroglycan null mutation in order to analyze dystroglycan's role in cardiac basement membrane assembly and cardiac function. The second aim is to investigate the regulation of the dystroglycan complex by the sarcoglycans in vascular smooth muscle of the heart. For this aim mice with a specific deficiency in delta-sarcoglycan in smooth muscle will be produced. Specific aims three and four identify the mechanisms of enteroviral protease 2A mediated cleavage of dystrophin and determine the significance of this cleavage in the intact heart. The complimentary approach is outlined in these specific aims will yield a new understanding of the role of dystrophin-glycoprotein complex in both hereditary and acquired cardiomyopathy. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen
Studies 33
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Project Title: EFFICACY AND SAFETY OF OXANDROLONE FOR BOYS WITH DUCHENNE'S MUSCULAR DYSTROPHY Principal Investigator & Institution: Pestronk, Alan; Professor; Washington University Lindell and Skinker Blvd St. Louis, MO 63130 Timing: Fiscal Year 2001 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: EMERIN FUNCTIONS IN TRANSCRIPTIONAL REGULATION Principal Investigator & Institution: Holaska, James M. Cell Biology and Anatomy; Johns Hopkins University 3400 N Charles St Baltimore, MD 21218 Timing: Fiscal Year 2003; Project Start 01-MAY-2003; Project End 30-APR-2005 Summary: (provided by applicant): The presence of the nuclear envelope in eukaryotes functionally separates the processes of transcription and translation. The ability to have these processes disjoined serves to establish greater transcriptional and translational regulation. The nuclear envelope consists of an outer nuclear membrane, which is contiguous with the endoplasmic reticulum, and an inner nuclear membrane (INM). The INM contains numerous integral membrane proteins that bind to both lamins and chromatin-associated proteins. One of these proteins, emerin, directly binds the nuclear lamina and a chromatin associated protein named Barrier-to-Autointegration (BAF). Interestingly, mutation or deletion of emerin causes the recessive form of EmeryDreifuss muscular dystrophy (EDMD). Although emerin is expressed in most cell types tested, EDMD specifically targets muscle and adipose tissue, suggesting a role for emerin in tissue-specific functions. Recently it has been demonstrated that another INM protein, Lap213, interacts with a transcriptional repressor, germ-cell-less (GCL). Since Lab2beta and emerin share a significant region of homology, I tested whether emerin could interact with transcriptional repressors. Both GCL and EBP1, another transcriptional regulator, bind emerin. I propose that emerin may recruit transcriptional regulators to the nuclear envelope and form functional repressor or activator complexes here. To test this model, I will fine-map the functional domains within emerin, GCL, and EBP1 necessary for this interaction. Using mutational analysis, I will identify the domain(s) in emerin that interact(s) with GCL and EBP1. Mutations will also be made in GCL and EBP in order to map the 'emerin binding domain' in each of these proteins. Once identified, the(se) emerin binding domain(s) will be used to identify other emerin binding proteins. The initial characterization of these interactions will serve as the foundation for studying the role of the nuclear envelope in transcriptional regulation in my own laboratory. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen
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Project Title: ENHANCEMENT OF MYOBLAST CHEMOTACTIC MIGRATION Principal Investigator & Institution: Dominov, Janice A.; Boston Biomedical Research Institute 64 Grove St Watertown, MA 02472 Timing: Fiscal Year 2002; Project Start 26-SEP-2002; Project End 30-JUN-2004 Summary: (provided by applicant): Genetic defects underlying several degenerative muscle diseases such as Duchenne muscular dystrophy (DMD) are known, yet effective therapies for these disorders have not been found. One approach has been cell-based therapy in which normal myoblasts or genetically modified patient myoblasts are injected into diseased muscle with the intent that engraftment would be sufficient to
34 Muscular Dystrophy
compensate for protein deficiencies. Little success has been achieved with this approach however due to problems such as poor graft survival and impractical requirements for numerous muscle injections. Recently, systemic delivery of muscle precursor cells via tail vein or arterial injection in mice has been demonstrated resulting in low-level donor cell engraftment of regenerating muscle tissue. Vascular migration and extravasation of precursor cells thus occurs and could provide a useful route for improved cell-based therapy for these devastating diseases. The specific aims of the proposed work are to 1) Identify molecules expressed in myoblasts that are involved in the attachment to activated endothelial cells and promote trans-endothelial cell migration, 2) Improve the efficiency of myoblast trans-endothelial migration, if possible, by cytokine-induced expression of molecules known to regulate attachment and extravasation of immune system cells. Methods: Murine skeletal muscle myoblasts will be studied to determine expression levels of proteins known to function in leukocyte extravasation. Inflammatory cytokines will be used to induce myoblast expression of proteins relevant to chemotactic movement. In vitro trans-endothelial cell migration assays will be used to assess the role of specific chemokines, receptors and cell adhesion molecules in this process and the influence of inflammatory cytokine stimulation on myoblast migration. Normal myoblasts and those induced by cytokines will be injected into tail veins of mdx mice (model for DMD) undergoing muscle regeneration and extravasation into tissues assessed. Results will further our understanding of the mechanisms that promote systemic engraftment of donor myoblasts into diseased muscle could significantly advance the therapeutic use of myogenic precursor cells for the treatment of muscular dystrophy. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •
Project Title: EPSILON-SARCOGLYCAN & PATHOGENESIS OF MUSCULAR DYSTROPHY Principal Investigator & Institution: Kobayashi, Yvonne M. Cardiovascular Center; University of Iowa Iowa City, IA 52242 Timing: Fiscal Year 2002; Project Start 05-AUG-2002 Summary: (provided by applicant): The long-term objectives of this research proposal are to elucidate the function of epsilon-sarcoglycan within the epsilon-beta-gamma-delta sarcoglycan complex, as well as at the sarcolemma, and how its function works together with the functional role of the dystrophin-glycoprotein complex in the pathogenesis of muscular dystrophy. Epsilon-sarcoglycan has 43 percent amino acid sequence identify with alpha-sarcoglycan, and like alpha-sarcoglycan, interacts with beta-gamma, and delta-sarcoglycans at the sarcolemma. In genetically engineered alpha-sarcoglycan deficient mice, there is a decrease in beta-gamma- and delta-sarcoglycans at the sarcolemma, but no change in epsilon-sarcoglycan. However, in beta- and gammasarcoglycan deficient mice, there is little to no detection of beta-, gamma-, and deltasarcoglycans and a severe decrease in epsilon-sarcoglycan at the sarcolemma. These data indicate that epsilon-sarcoglycan forms a separate complex with beta-, gamma-, and delta-sarcoglycans and suggests that epsilon-sarcoglycan plays a pivotal role in the pathogenesis of muscular dystrophy. To test this hypothesis, I have proposed the generation and analysis of different genetically modifiable systems: gene-targeted disruption of epsilon-sarcoglycan in mice, transgenic epsilon-sarcoglycan mice with targeted over expression in striated muscle, and embryonic stem cells homozygous for the deletion of epsilon-sarcoglycan. I also describe the use of epsilon-sarcoglycan recombinant adenovirus for adenovirus-mediated focal gene transfer to rescue the sarcoglycan complexes? functions. Furthermore, I describe the characterization of the
Studies 35
interactions between the sarcoglycan components to further understand the structural and functional relationship between the sarcoglycan components to further understand the structural and functional relationship between the components of the epsilon-betagamma-delta sarcoglycan complex and how this compares to that of the alpha-betagamma-delta sarcoglycan complex. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •
Project Title: EVALUATION OF CLINICAL APPLICATIONS OF ELASTOGRAPHY Principal Investigator & Institution: Garra, Brian; University of Texas Hlth Sci Ctr Houston Box 20036 Houston, TX 77225 Timing: Fiscal Year 2001 Summary: The objectives of the project are to demonstrate in a statistically valid number of patients, the clinical utility of the new technique of ELASTOGRAPHY is an adjunct diagnostic tool for the diagnosis of benign and malignant breast masses. Currently, mammography is the primary screening tool for the diagnosis of breast cancer. It is sensitive but often not very specific with approximately 75% of the masses biopsied being non-cancerous. Recently sonography has been shown to be a useful tool for distinguishing solid from cystic masses and for diagnosis solid masses. But often the sonographic features that distinguish benign form malignant masses are subtle and subjective in nature. Elastography is a technique that uses the raw ultrasound signal to produce an image of HARDNESS of breast tissue rather than the normal sonographic image of backscatter intensity. Because breast cancers have long been known to be significantly harder than normal breast tissue and benign breast masses, elastography promises to be helpful in distinguishing benign from malignant masses. Preliminary studies in over 100 patients with biopsy proven breast masses has shown that elastography can reliable identify breast cancers and can distinguish cancers from benign masses in most cases. Using a subjective index of brightness on the elastogram plus the difference in transverse dimension on a mass on elastography and sonography, 11 of 15 benign masses could be classified as definitely benign without incorrectly classifying any cancers as benign. Using these two features, the area of the ROC curve (Az) was 0.86 performance similar to the PAP smear for cervical cancer. The number of cases in the preliminary study was small and only a single observer was used. The current proposal outlines a two center unblinded level of suspicion trial that will demonstrate whether elastography plus mammography and sonography increases the diagnostic confidence of readers for breast cancer and benign masses. Also, a blinded rereading study is proposed that will demonstrate the performance of each modality alone and in conjunction with the other modalities. The number of patients to be studied (about 750) will be sufficient to estimate Az to a standard deviation of 0.02. Since elastography also may be helpful in other organs such as the thyroid, renal transplants, lymph nodes and muscles, pilot studies to evaluate the potential value of elastography in those organs are also proposed. The overall hypothesis is: Elastography is capable of differentiating normal and abnormal tissues, including cancer, in an in vivo clinical environment. The overall hypothesis is: Elastography is capable of differentiating normal and abnormal tissues, including cancer, in an in vivo clinical environment. Specific Aims of the Project are: 1. Establish and define the elastographic properties of normal and abnormal breast tissue in vivo. 2. Conduct a clinical study to explore the potential role of elastography in breast cancer diagnosis. 3. Explore in vivo elastography animal models of normal and abnormal tissues. Specific studies will include normal canine prostate, canine prostate carcinoma, and woodchuck hepatoma models. 4.
36 Muscular Dystrophy
Explore the application of elastography to other superficial organs in humans such as thyroid, testicles, muscles, and renal transplants. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •
Project Title: EXCITATION-CONTRACTION COUPLING IN DYSTROPHIC MUSCLE Principal Investigator & Institution: Vergara, Julio L. Professor; Physiology; University of California Los Angeles 10920 Wilshire Blvd., Suite 1200 Los Angeles, CA 90024 Timing: Fiscal Year 2003; Project Start 01-APR-2003; Project End 31-MAR-2008 Summary: (provided by applicant): Abnormalities in the mechanisms of calcium regulation and excitation-contraction (EC) coupling that may be linked to the degeneration of skeletal muscle fibers in Becker Muscular Dystrophy (BMD) and in Duchenne Muscular Dystrophy (DMD) will be investigated using isolated muscle fibers from mdx mice. Cells from this animal model, like those of dystrophic patients, have deficiencies in the expression of the protein dystrophin. Although there is substantial biochemical evidence demonstrating the association of the dystrophin-glycoprotein complex with transmembrane- and membrane-bound muscle proteins, little is known about its specific role in the physiological aspects of a muscle fiber. The main goal of this proposal is to obtain critical experimental evidence linking the absence of dystrophin with specific alterations in the electrical propagation in the transverse tubular system and calcium signaling machinery. Several possibilities that may explain these observations will be explored experimentally. Changes in intracellular calcium concentration triggered by electrical activity of the muscle fibers will be recorded with the aid of low affinity calcium sensitive fluorescent indicators and membrane potential changes in the transverse tubules will be monitored with potentiometric indicators. The investigations will be carried out using high-resolution optical methods that permit to assess the functional state of these critical steps of the EC coupling process, not only at the cellular level, but also within sub-regions of the muscle fiber and even within a single sarcomere. We will perform these measurements across three different age groups of the mdx mouse in order to understand the progression of the disease with time. We will also test if muscle fibers from a utrophin/dystrophin-lacking double mutant mouse, which exhibits a harsher pathology (similar to DMD), show signs of more pronounced defects in EC coupling. These types of experiments are necessary to unravel the mysterious role that dystrophin may play in the normal regulation of calcium metabolism in skeletal muscle. The knowledge gained in the proposed studies will help to elucidate the functional role of dystrophin in mammalian skeletal muscle, to this date the most fundamental and elusive problem in muscular dystrophy research. The enhanced methods proposed to detect defective steps in the EC coupling mechanisms within localized submicroscopic regions of mammalian muscle fibers may become the optimal choice for the future evaluation of genetic therapeutic procedures in sub-regions of a single muscle cell. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen
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Project Title: FACIOSCAPULOHUMERAL MUSCULAR DYSTROPHY (FSHD) TISSUE BANK Principal Investigator & Institution: Tawil, Rabi; University of Rochester Orpa - Rc Box 270140 Rochester, NY 14627 Timing: Fiscal Year 2001 Summary: This abstract is not available.
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Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •
Project Title: REGULATOR
FACTOR
X--A
CARDIAC-SPECIFIC
TRANSCRIPTIONAL
Principal Investigator & Institution: Ordahl, Charles P. Professor; Anatomy; University of California San Francisco 500 Parnassus Ave San Francisco, CA 94122 Timing: Fiscal Year 2001; Project Start 01-APR-1997; Project End 31-JAN-2006 Summary: (appended verbatim from investigator's abstract): Although skeletal muscle accounts for a large fraction of the body mass, it is one of the least regenerative of tissues. Satellite cells, which reside within the basal lamina of mature skeletal muscle fibers, are capable of mitotic expansion thereby generating new adult myoblasts to effect local repair of injured or diseased muscle. Such adult myoblasts, however, are not capable of replacing large losses of muscle tissue that occur through injury or as a consequence of chronic muscle disease, such as Duchenne's muscular dystrophy. Even after in vitro enrichment and implantation into injured muscle sites, such adult myoblasts evidence little incorporation and integration into organized muscle tissue. Ideal cells that could be used in muscle replacement therapy should be capable of: (1) large mitotic expansion potential through stem cell activity; (2) morphogenetic capacity (involving complex intra-tissue and extra-tissue interactions); (3) migratory capacity (short and long distance). At present, neither a source of such cells nor an effective muscle replacement strategy is available. These qualities are possessed by the embryonic cells that build the muscle primordia of the body. During the previous 3 years of this project we have identified, Isolated and otherwise analyzed a novel class of embryonic muscle stem cells that we name mvogenic progenitor cells (MP cells). MP cells are distinct from satellite cells in their ability to undergo migration and morphogenetic movements. MP cells are distinct from their earlier embryonic counterparts, typically referred to as "embryonic stem cells," in that they are not multipotent but are developmentally restricted to the formation of skeletal muscle tissue only. Most importantly, after transplantation from one embryo to another, MP cells act in a semiautonomous fashion to generate organized muscle tissue, even under nonpermissive conditons. Thus, MP cells retain intrinsic determined qualities that allow them to form muscle tissues even in localities that are inappropriate or even hostile. Thus, embryonic MP cells possess the qualities required for cells to be used for muscle replacement therapy. In the present proposal, we will isolate MP cells from avian embryos and analyze their cellular, tissue, and molecular properties. These studies will lead to a deeper understanding of the processes by which muscle tissue is formed in both normal and abnormal development. More important from a potential therapeutic point of view however, the properties discovered about MP cells from this study will provide a foundation for the engineering of their essential properties into other cells, such as satellite cells, for their potential use in myoblast transfer or other therapies. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •
Project Title: FSHD CHROMATIN
SYNDROME--DNA
REPEATS,
METHYLATION,
AND
Principal Investigator & Institution: Ehrlich, Melanie; Human Genetics Program; Tulane University of Louisiana New Orleans, LA 70118 Timing: Fiscal Year 2001; Project Start 30-SEP-2001; Project End 31-AUG-2004 Summary: (provided by applicant): Fascioscapulohumeral muscular dystrophy (FSHD) is an unusual autosomal dominant syndrome caused by the loss of some copies of a
38 Muscular Dystrophy
complex repeat (D4Z4) in a subtelomeric region (4q35) of one chromosome 4 homologue. The number of copies of this 3.3-kb repeat at 4q35 is polymorphic. Unaffected individuals have 11 to about 95 copies on each allelic 4q35. In contrast, more than 90% of FSHD patients have less than 10 copies at one of these allelic 4q subtelomeric regions. It has been proposed by many investigators that normally this region is heterochromatic but that when the number of tandem copies of D4Z4 is less than 10, the region loses its condensed chromatin structure, This loss of heterochromatinization, in turn, is hypothesized to induce inappropriate gene expression in the affected muscle cells. However, there have been no reports about studies of the chromatin structure in this region for normal or FSHD cells. In the planned research, immunochemical, cytochemical, and immunocytochemical methods will be used to examine whether this region is indeed heterochromatic and whether it loses the heterochromatic structure when it contains the FSHD deletion. Myoblast cultures and lymphoblastoid cell lines from normal individuals and FSHD patients will be studied. These experiments will include analysis of histone acetylation and binding of heterochromatin 1 beta protein to the D4Z4 chromatin region. Also, we will determine whether this region is late-replicating in normal cells, as is the case for heterochromatin. Consistent with the proposed heterochromatic nature of this region, it has recently been shown that this repeat is highly methylated. The preliminary study of methylation of the D4Z4 repeat will be expanded to examine whether this repeat is no longer hypermethylated in the deletion-containing chromosome 4 in FSHD cells. It has recently been shown that cells from another genetic syndrome, ICF (a DNA methyltransferasedeficiency and chromosome instability syndrome), are undermethylated in this repeat. Because abnormal hypomethylation can favor chromosome rearrangements, ICF and normal cell lines will be compared for the frequency of rearrangements in this region. The proposed research should help elucidate the molecular etiology of the enigmatic FSHD syndrome. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •
Project Title: FUNCTION OF THE SYNTROPHIN/DYSTROPHIN INTERACTION Principal Investigator & Institution: Froehner, Stanley C. Professor and Chair; Physiology and Biophysics; University of Washington Seattle, WA 98195 Timing: Fiscal Year 2001; Project Start 01-APR-1995; Project End 31-AUG-2004 Summary: (from applicant's abstract) Syntrophins are modular adapter proteins, whose importance can be inferred from their association with dystrophin, the product of the Duchenne and Becker muscular dystrophy gene. In skeletal muscle, dystrophin is associated with a complex of transmembrane glycoproteins and peripheral membrane proteins that link the extracellular matrix to cytoskeletal actin. A multitude of muscle pathologies results from mutations in proteins of the dystrophin complex. All syntrophins, of which four are now known, have a characteristic domain structure: two pleckstrin homology (PH) domains, a PDZ domain and a domain unique to syntrophin (SU domain. We have shown that the tandem PH2SU domain binds to dystrophin and that syntrophin PDZ domains bind ion channels (sodium channels, certain potassium channels) and neuronal nitric oxide synthase (nNOS), thereby linking them to the dystrophin complex. In this application, we will test the hypothesis that syntrophins confer a membrane signaling function on the dystrophin complex and that the syntrophin PDZ domains are especially important. We will use biochemical and molecular biological methods to identify additional syntrophin binding proteins, including ones that associate via non-PDZ interactions. The importance of syntrophin in the association of syntrophin with agrin-induced acetylcholine receptor clusters will be
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examined in cultured myotubes. To examine the function of syntrophin interactions with skeletal muscle ion channels, we have developed genetically-altered mice lacking alpha- and b2-syntrophin. We now propose to study the effects of syntrophin deficiency on acetylcholine receptor clustering and on sodium channel distribution and physiology. Finally, the importance of syntrophins in muscle pathology will be examined. We will compare muscle abnormalities in the genetically-altered mice with mdx mouse and determine if muscle activity (in the form of exercise) exacerbates degeneration. These studies are expected to expand our understanding of the syntrophin complex as an organizing center for transmembrane signaling proteins and define the role of syntrophins in the complex. A role for syntrophin abnormalities in human muscle pathologies may also be revealed. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •
Project Title: FUNCTION OF THE WW DOMAIN OF DYSTROPHIN Principal Investigator & Institution: Sudol, Marius; Biochem and Molecular Biology; Mount Sinai School of Medicine of Nyu of New York University New York, NY 10029 Timing: Fiscal Year 2001; Project Start 15-AUG-2000; Project End 31-JUL-2003 Summary: (appended verbatim from investigator's abstract): Duchenne and Becker muscular dystrophies are caused by genetic lesions of the dystrophin gene. These mutations result in the production of an abnormal protein or its absence. The long term goal of our research is to fully characterize the function of dystrophin to facilitate early detection, treatment and perhaps prevention of muscular dystrophy. During the last three years, we have identified and characterized a protein module, the WW domain, which binds proline rich ligands. The WW domain is present within the carboxyterminal region of dystrophin. Dystrophin interacts with several proteins including B-dystroglycan, which spans the membrane and communicates with the extracellular matrix. The overall hypothesis to be evaluated is that the WW domain, EF hands and the ZZ domain of dystrophin mediate interaction with B-dystroglycan in vivo, and that without this interaction, a partial or complete dystrophic phenotype results at the level of organism. Our specific aims are: 1. To characterize the specificity of the interaction between the WW domain of dystrophin and the proline rich core of Bdystroglycan using site directed mutagenesis, phage displayed peptide repertoires, the SPOT technique of peptide synthesis, and immunoprecipitation. 2. To elucidate the role of the cysteine rich region of dystrophin in modulating the interaction between the WW domain, EF hands plus the Z domain of dystrophin and B-dystroglycan by mutational analysis and x-ray crystallography. 3. To provide evidence of the biological role of modular protein domains of dystrophin (the WW domain, EF hands, the Z domain) by showing that dystrophin transgenes in which any of the four domains alone or in combination with other modules is point mutated can only partially complement the mdx phenotype (muscular dystrophy in mice), in contrast to the control, a wild type transgene, which fully complements the mdx phenotype. These studies will provide insight into molecular function of dystrophin and could point towards potential therapies for Duchenne and Becker muscular dystrophies. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen
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Project Title: FUNCTIONAL TETRAHYMENA
ANALYSIS
OF
CALCIUM
STORES
IN
Principal Investigator & Institution: Turkewitz, Aaron P. Associate Professor; Molecular Genetics & Cell Biol; University of Chicago 5801 S Ellis Ave Chicago, IL 60637
40 Muscular Dystrophy
Timing: Fiscal Year 2001; Project Start 01-FEB-2000; Project End 31-JAN-2004 Summary: Exocytosis of secretory dense-core vesicles in many cell types is triggered by a transient elevation of cytosolic calcium that is mobilized from intracellular reservoirs. The best characterized calcium reservoirs are the endoplasmic reticulum (ER) and specialized ER-like organelles. Both the structure of reservoirs as well as the organization of the proteins within them are likely to contribute to the efficiency and specificity of signaling. One indication of this is that calcium is not uniformly distributed throughout the ER, implying that sub-regions may differ in signaling potential. Calcium-rich domains may be generated by the non-random distribution of specific proteins with the membrane and lumen of these reservoirs. This has not been tested, nor are the bases for such sub-regions known. Our aim is to develop further a system in which individual proteins can be identified and analyzed both in vitro and in vivo, to address these issues. The ciliate Tetrahymena thermophila offers a host of experimental advantages for studying such mechanisms. In this proposal, we focus on an ER-like network in ciliated protists, called the alveoli, that has evolved to facilitate signaling at the cell surface. Alveolar calcium is released when cells undergo stimulation with secretagogues, and the increase in cytosolic calcium triggers exocytosis of regulated secretory vesicles. In Tetrahymena, all such vesicles are tethered at the plasma membrane and undergo synchronous membrane fusion. From the experimental perspective, this provides an ideal read-out of alveolar signaling activity. We propose to study the function of individual alveolar proteins in exocytic signaling in Tetrahymena, taking advantage of homologous recombination for in vivo analysis. To begin, we have developed a cell-free alveolar preparation that is active in calcium transport. Our first aim is to isolate biochemically the calcium buffer proteins (homologs of vertebrate calsequestrins) that reside in the alveolar lumen, and clone the corresponding genes. This will be a starting point for mutational analysis of in vivo function, using gene replacement. Other proteins that modulate calcium flux in alveoli will be identified based on direct or indirect genetic screens. The long-term aim of this work is to develop an understanding of how proteins in intracellular reservoirs contribute to calcium signaling and homeostasis. Such questions are medically important for at least two reasons. First, defects in calcium homeostasis may be a direct cause of muscle necrosis in muscular dystrophy, in which prolonged high cytosolic levels can trigger apoptosis. Secondly, a detailed understanding of alveoli in particular might be a basis for intervention against parasites belonging to the Alveolate lineage, including the organisms responsible for malaria, cryptosporodiosis, and toxoplasmosis. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •
Project Title: FUNCTIONAL ANALYSIS OF LEM-DOMAIN NUCLEAR PROTEINS Principal Investigator & Institution: Wilson, Katherine L. Associate Professor; Cell Biology; Johns Hopkins University 3400 N Charles St Baltimore, MD 21218 Timing: Fiscal Year 2002; Project Start 01-MAY-2002; Project End 30-APR-2006 Summary: Emerin is a nuclear membrane protein that bines lamina filaments. Emerin mutations cause Emery-Dreifuss muscular dystrophy, affecting heart, skeletal muscle, and tendons. Emerin belongs to the conserved LEM-domain family of nuclear proteins. The LEM-domain of emerin binds BAF (barrier to autointegration factor), a conserved chromatin protein of unknown function. We propose that LEM proteins structurally link chromatin (via BAF) to the lamina, and also bind partners that mediate DNA replication or transcriptional repression. We propose to determine the essential function of three conserved LEM proteins in C.elegans: emerin, MAN1 and lem-3. In C. elelgans, all or most cells express emerin and MAN1, but the RNAi-induced loss of emerin or MAN1
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has no phenotype. However, loss of both proteins is lethal in embryos. Thus, emerin and MAN1 have essential function(s). We will test the hypothesis that all three LEM proteins bind directly to BAF and lamin, and use site-directed mutagenesis to map their binding regions. We will use RNAi to deplete each LEM protein, and pairs of LEM proteins to test for overlapping and cell-type-specific functions in vivo. By identifying and characterizing new binding partners for emerin, MAN1 and lem- 3, we will test our hypothesis that LEM proteins are directly involved in replication, transcription, or lamin dynamics. We will determine if mutant LEM proteins, whose binding activities are defined in vitro, can rescue lethality of emerin: MAN1 (RNAi) embryos. WE will screen for mutations that are synthetically lethal in an emerin null or MAN1 null background, to identify proteins that mediate the essential functions of emerin and MAN1. This work will be the first genetic analysis of the nuclear lamina. Our work will yield basic knowledge about the functions of LEM proteins, and their interactions with lamins and BAF. This work can be extended to humans to predict the molecular mechanisms of heart disease and muscular dystrophy caused by loss of emerin. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •
Project Title: FUNCTIONAL ULTRASTRUCTURE OF THE NERVOUS SYSTEM Principal Investigator & Institution: Salpeter, Edwin E. Neurobiology and Behavior; Cornell University Ithaca Office of Sponsored Programs Ithaca, NY 14853 Timing: Fiscal Year 2001; Project Start 01-JUN-1975; Project End 30-APR-2003 Summary: Verbatim from the Applicant's Abstract): The neuromuscular junction (nmj) is used as a model synapse to study an important aspect of synaptic regulation. The innervated adult nmj is a very stable synapse both morphologically and metabolically. Changes are constantly occurring during development and during aging, but its integrity is maintained to a large extent by neural innervation. A longterm aim of this proposal is to understand how the nerve maintains the structure and function of a stable nmj. One manifestation of the junctional stability is the presence of acetylcholine receptors (AChRs) at a very high density and slow degradation rate (t 1/2 about 10 days). It is well known that during development or in the reinnervation of a denervated nmj there is a replacement of a rapidly degrading, gamma subunit-containing, AChR population (Rr), by a slowly degrading epsilon subunit-containing, AChR population (Rs). The specific aims of this research are i) to test hypotheses regarding the possible stages in producing and maintaining nmj stability, ii) to establish the role played by, the AChR subunit composition, and phosphorylation of the epsilon subunit, and iii) to identify neural factors and cytoskeletal elements involved in establishing AChR stability. The role of the two AChR populations (Rr and Rs), differing in degradation properties, will be assessed. Studies will involve electron microscope autoradiography and immunocytochemistry, in vivo studies, in vitro tissue and organ culture preparations and molecular approaches. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen
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Project Title: GENE AND CELL THERAPY OF DUCHENNE MUSCULAR DYSTROPHY Principal Investigator & Institution: Glorioso, Joseph C. Professor and Chairman; Molecular Genetics & Biochem; University of Pittsburgh at Pittsburgh 350 Thackeray Hall Pittsburgh, PA 15260 Timing: Fiscal Year 2003; Project Start 30-SEP-2003; Project End 31-AUG-2008
42 Muscular Dystrophy
Description (provided by applicant): The proposed study represents a systematic approach to recruit subjects and develop outcome measures necessary to reach a phase I gene transfer trial in Duchenne muscular dystrophy (DMD) and in two forms of limb girdle muscular dystrophy [LGMD 2D or alpha-sarcoglycan (SG) deficiency, and LGMD 2E or beta-SG deficiency]. The prepatory stage will be carried out in years one through three of the proposal. In years four and five, Phase 1 clinical transfer trials will be done in these three forms of muscular dystrophy. The specific aims define the approach to reach the stated goals: Specific Aim 1: Identify a cohort of DMD subjects with small gene mutations to participate in Phase 1 gene transfer studies Specific Aim 2: Establish the most appropriate muscle(s) for gene transfer in a population of DMD subjects using magnetic resonance imaging (Aim 2A) and quantitative muscle strength testing (maximum voluntary isometric contraction testing or MVICT) (Aim 2B) Specific Aim 3: Identify a population of LGMD 2D (alpha-SG) and LGMD 2E (beta-SG) subjects for participation in Phase 1 gene transfer studies Specific Aim 4: Establish the most appropriate muscle(s) for gene transfer in a population of LGMD 2D and LGMD 2E subjects using magnetic resonance imaging (Aim 4A) and quantitative muscle strength testing (MVICT) (Aim 4B) Specific Aim 5: Establish appropriate delivery methods for gene transfer of adeno-associated virus (AAV) considering volume, rate, and spread of vector from the site of injection Specific Aim 6: Perform Phase 1 gene transfer trials in DMD and two forms of LGMD (2D alpha-SG) and (2E beta-SG) Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •
Project Title: GENE CAUSING PAGET & LIMB-GIRDLE MUSCULAR DYSTROPHY Principal Investigator & Institution: Kimonis, Virginia E. Pediatrics; Southern Illinois University Sch of Med Box 19616, 801 Rutledge St Springfield, IL 62794 Timing: Fiscal Year 2001; Project Start 15-FEB-2001; Project End 31-AUG-2001 Summary: (Taken from the application): Limb-Girdle Muscular Dystrophy (LGMD) encompasses a clinically diverse group of disorders characterized by proximal muscle weakness first affecting the hip and shoulder girdle elevated creatinine kinase values, and non-specific changes in the muscle biopsy. In addition to clinical heterogeneity within the LGMD category, genetic heterogeneity is indicated by the existence of dominant and recessive forms. We have identified a large family with autosomal dominant LGMD and early onset Paget disease of bone (PDB). These individuals have bone pain in the hips, shoulders and back from the Paget disease. Individuals eventually become bed bound and die prematurely from progressive muscle weakness +/cardiomyopathy in their forties to sixties. Laboratory investigation indicates elevated alkaline phosphatase levels in affected individuals. CPK is normal to mildly elevated. Muscle biopsy of the oldest affected male revealed non-specific changes and vacuolated fibers. Preliminary molecular analysis excluded linkage to the known loci for the autosomal dominant and recessive forms as well as 2 loci for autosomal dominant PDB and 6 loci for cardiomyopathy. Exclusion of the candidate loci prompted a genome-wide scan of 39 family members (9 affected, 24 unaffected, 6 spouses} with 402 polymorphic microsatellite markers (Marshfield Genotyping Services). The disease locus was linked to chromosome 9p21-q21 with marker D9S301 (max LOD=3.64), thus supporting our hypothesis that this family displays a genetically distinct form of Limb-GirdleMuscular-Dystrophy associated with Paget disease of bone and cardiomyopathy. Subsequent haplotype analysis with a high density of microsatellite markers flanking D9S301 refined the disease locus to a 3.76 cM region on chromosome 9p21-13.2. This region excludes the IBM2 locus for autosomal recessive vacuolar myopathy. Two candidate genes mapped to the critical region, NDUFB6 and IL-11RA, are being
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examined for disease-associated mutations. NDUFB6 encodes a subunit of Complex I of the mitochondrial respiratory chain and the IL11RA gene product influences proliferation and differentiation of skeletogenic progenitor cells. Identification of the genes involved in the LGMDs has led to the elucidation of an entire family of proteins that function in the dystrophin-glycoprotein complex. and a basis for understanding the pathophysiology of this complex. Delineation of the genetic component responsible for the LGMD/PDB phenotype should promise similar insight and facilitate in the design of novel treatment protocols for the two disorders. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •
Project Title: GENE EXPRESSION % MUSCLE DEVELOPMENT IN MYOTUBULAR MYOPATHY Principal Investigator & Institution: Beggs, Alan H. Associate Professor of Pediatrics; Children's Hospital (Boston) Boston, MA 021155737 Timing: Fiscal Year 2001; Project Start 25-SEP-2001; Project End 31-AUG-2006 Summary: (provided by applicant): The long term goals of this project are to understand the molecular basis for myotubular myopathy (MTM) and its defect in muscle differentiation and to use this information to develop therapies for patients with this neuromuscular disease. X-linked MTM (XLMTM), and its milder variant, centronuclear myopathy (CTNM), are a clinically and genetically heterogeneous group of disorders characterized by congenital skeletal muscle weakness that varies from rapidly fatal in the infantile period (XLMTM) to relatively nonprogressive and compatible with normal life span (CTNM). The unifying features are skeletal muscle weakness and myopathic findings on muscle biopsy, including the presence of undifferentiated-appearing small myofibers with characteristic central nuclei or a central clear zone corresponding to the internuclear space ("myotubes"). XLMTM is caused by mutations of myotubularin, a novel dual specificity protein phosphatase whose role in muscle differentiation is unknown. To better understand myotubularin function and muscle development in general, we propose to 1) characterize SP stem cells in XLMTM muscle, 2) develop gene expression profiles for XLMTM myoblasts and muscle at various stages of differentiation, and 3) use this information to identify and characterize new proteins and pathways involved in muscle differentiation. Comparison of XLMTM-associated changes in gene expression with changes in CTNM and other congenital myopathies and dystrophies will allow identification of disease-specific changes. Correlation with data on various muscular dystrophies studied by other components of this Program Project will allow determination of non-dystrophic and dystrophy-specific pathogenic pathways. Knowledge of XLMTM-specific gene expression abnormalities will help in identifying downstream consequences of myotubularin dysfunction providing potential specific targets for therapeutic interventions to treat this disease. Furthermore, better knowledge of myotubularin's role in muscle differentiation will help in identifying candidate genes for the milder related disease CTNM as well as shed light on normal muscle differentiation. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen
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Project Title: GENE EXPRESSION % THERAPEUTIC APPLICATION OF MUSCLE STEM CELLS Principal Investigator & Institution: Gussoni, Emanuela; Children's Hospital (Boston) Boston, MA 021155737 Timing: Fiscal Year 2001; Project Start 25-SEP-2001; Project End 31-AUG-2006
44 Muscular Dystrophy
Summary: (provided by applicant): The broad objectives of this proposal are to characterize human muscle stem cells and evaluate their potential as gene vectors for the therapy of muscle disorders. The aims of these studies are to 1) Purify muscle stem cells from human skeletal muscle, using the vital DNA dye Hoechst 33342 (H0342) and the fluorescence-activated cell sorter (FACS); 2) Use gene chip and gene array technologies to characterize the repertoire of genes expressed by human muscle stem cells and compare this to expression patterns in more differentiated myoblasts; 3) Analyze and characterize expressed genes that are specific to muscle stem cells to define possible pathways of differentiation/commitment of skeletal muscle stem cells; 4) Use the information derived from gene array technology to optimize different media compositions that will promote the propagation of human muscle stem cells in vitro; 5) Test whether human muscle stem cells can differentiate into multiple cell types in vivo by introducing them into NOD /SCID mice and assessing their ability to reach host skeletal muscles from the circulation. These studies are essential to further our basic knowledge on the existence of muscle stem cells in humans. The identification of candidate genes that are uniquely expressed by human muscle stem cells will help in understanding how muscle stem cells differ from more committed myoblasts, and start to unravel why muscle stem cells (at least from previous mouse studies) can differentiate into bone marrow. Further, exploring methods to propagate muscle stem cells will be crucial to obtain large numbers of cells for characterization experiments as well as in vivo studies. These in vivo studies are aimed to test whether human muscle stem cells can be safely used as vehicles to systemically deliver genes to skeletal muscle. The hope is to be able to extend the practical use of muscle stem cells in the development of a therapy for human muscle disorders. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •
Project Title: GENE EXPRESSION AND DYSFERLIN-RELATED DYSTROPHIES Principal Investigator & Institution: Brown Jr, Robert H.; Children's Hospital (Boston) Boston, MA 021155737 Timing: Fiscal Year 2001; Project Start 25-SEP-2001; Project End 31-AUG-2006 Summary: (provided by applicant): Limb girdle muscular dystrophy type 2B (LGMD 2B) and Miyoshi myopathy (MM) are caused by defects in a gene that encodes a newly identified protein "dysferlin". The long-term objectives of this proposal are to characterize the biological properties of dysferlin and its role in the pathogenesis of LGMD 2B and MM and to initiate studies of cell therapy in these diseases. The specific aims are to: (1) Characterize dysferlin gene mutations and abnormalities of dysferlin protein expression in patients with MM and LGMD 2B and use this information to extend our studies of dysferlin as a novel muscle membrane protein. (2) Use conventional methods (immunoprecipitation, yeast two-hybrid analyses) to identify proteins that interact with normal and mutant dysferlin. (3) Use chip-based mRNA expression arrays to analyze dysferlin-deficient human muscle to identify changes of muscle gene expression that are either common to all dystrophies or specific to the dysferlinopathies. (4) Validate results of expression arrays and characterize genes that are unique to each of the dystrophies and begin to test new hypotheses about the molecular pathogenesis of muscle degeneration in the dysferlinopathies. (5) Analyze muscle stem cell (SP cell) populations in MM and LGMD-2B and the feasibility of SP therapy in a mouse model of dysferlin deficiency. These studies will be important because: (1) the dysferlinopathies constitute a significant proportion of all LGMD; (2) the studies in Aims 1-3 will illuminate aspects of the normal biological properties of this novel protein; (3) studies of pathological muscle in Aims 1-4 will contribute directly to
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understanding the pathogenesis of LGMD, MM and other muscular dystrophies (including facioscapulohumeral and myotonic dystrophy, included as comparative disease controls); and (4) the investigations in Aim 5 will contribute to the development of therapy for these types of muscular dystrophy. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •
Project Title: GENE EXPRESSION IN LIMB GIRDLE MUSCULAR DYSTROPHY Principal Investigator & Institution: Mcnally, Elizabeth M. Associate Professor; Medicine; University of Chicago 5801 S Ellis Ave Chicago, IL 60637 Timing: Fiscal Year 2003; Project Start 22-SEP-2003; Project End 31-AUG-2005 Summary: (provided by applicant): The muscular dystrophies are a genetically diverse group of disorders that lead to progressive muscle weakness and disability. In recent years, a number of genes have been discovered that, when mutated, lead to muscular dystrophy. In humans, mutations in the genes encoding sarcoglycan proteins produce Limb Girdle Muscular Dystrophy (LGMD). The sarcoglycan genes encode proteins each with a single transmembrane domain. Together, the sarcoglycan subunits form a subcomplex within the dystrophin glycoprotein complex (DGC). The DGC is important for stabilizing the cytoskeleton, the plasma membrane and the extracellular matrix. The loss of sarcoglycan from the plasma membrane causes degeneration to occur in both skeletal and cardiac muscle. Loss of function mutations in sarcoglycan genes causes muscle degeneration and abnormal muscle membrane permeability. Mouse models, engineered with sarcoglycan gene mutations, were found to target different aspects of sarcoglycan function (Hack et al. 1998; Hack et al. 1999; Hack et al. 2000). Mice lacking delta-sarcoglycan develop increased myocyte damage in response to the force of muscle contraction. In contrast, mice lacking gamma-sarcoglycan do not display increased myocyte damage in response to muscle contraction suggesting that gamma-sarcoglycan deficiency may cause membrane damage by a non-mechanical, or signaling, defect. Interestingly, skeletal and cardiac muscle degeneration is identical between mice lacking either gamma-sarcoglycan or delta-sarcoglycan. Therefore, these two different mouse models modify specific mechano signaling aspects of sarcoglycan function. We propose to conduct a microarray analysis of gene expression using gamma-sarcoglycan and delta-sarcoglycan mutant muscle to compare the changes in gene expression between these two forms of LGMD. The changes in gene expression in sarcoglycan mutant muscle will be compared to those found in dystrophin deficient muscle. Finally, we propose to analyze gene expression in cardiac tissue from gamma- and deltasarcoglycan mutant mice. Together, these experiments will outline the temporal profile of gene expression changes that arise in these disorders. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen
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Project Title: GENE EXPRESSION IN NORMAL & DISEASED MUSCLE DEVELOPMENT Principal Investigator & Institution: Kunkel, Louis M. Professor; Children's Hospital (Boston) Boston, MA 021155737 Timing: Fiscal Year 2001; Project Start 25-SEP-2001; Project End 31-AUG-2006 Summary: PROGRAM (provided by applicant): The last decade has witnessed remarkable progress in defining primary defects that cause inherited muscle disorders. The genetic heterogeneity of these diseases is enormous; mutations in more than 40 different genes are implicated. Many critical questions remain concerning the pathogenesis of muscle cell degeneration in these diseases and strategies for their
46 Muscular Dystrophy
treatment. This Program Project will use classical methods of gene and protein analysis and state-of-the-art gene expression array technology to study these questions. The investigators in this program have contributed importantly to the muscular dystrophy field. The proposed 4 projects have unique features but overlapping concepts and methodologies. Project 1 will study the dystrophin-associated complex of proteins, emphasizing the sarcoglycans and the newly described filamin-C. Project 2 will investigate the biology of dysferlin, its potential protein partners, and how these are altered by dysferlin gene mutations. Project 3 will examine the function of myotubularin in normal muscle development and the mechanisms by which its mutations cause developmental myopathies. Project 4 will study the biological and therapeutic properties of muscle stem cells. Three Cores will provide administrative oversight and services essential to the smooth progression of this program. Core B will coordinate sample acquisition and muscle RNA preparation for each project. Core C will perform the microarray analysis of gene expression and provide expertise in bioinformatics and data interpretation. The aim is to identify patterns of gene expression that are global in all dystrophies or distinct to specific sets of dystrophies and myopathies; this will provide insight into the molecular basis of normal muscle development and its dysfunction in these disease states. The long-term goal is to use this information in conjunction with the insights from studies of stem cell biology to devise new approaches to the treatment of the muscular dystrophies and related myopathies. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •
Project Title: GENE THERAPY FOR DUCHENNE MUSCULAR DYSTROPHY Principal Investigator & Institution: Wolff, Jon A. Professor; Pediatrics; University of Wisconsin Madison 750 University Ave Madison, WI 53706 Timing: Fiscal Year 2001; Project Start 30-SEP-2000; Project End 31-AUG-2005 Summary: (Copied from Applicant Abstract): Gene therapy promises to be a cure for the muscular dystrophies, such as Duchenne muscular dystrophy. Studies by my laboratory and others indicate that the transfer of the normal human dystrophin gene into dystrophic muscle (in the mouse model) prevents the death of the myofiber. The critical problem now is how to deliver the normal dystrophin gene to enough of the muscle cells and have it stably expressed in order to effect a cure. We have spectacular preliminary results that show that plasmid DNA can be delivered via a blood vessel into more than 10 percent of the muscle cells throughout the leg of a rat. This percentage of transfected muscle cells approaches the critical minimum percentage necessary to be curative in children with Duchenne muscular dystrophy. With this approach, multiple administrations should be possible, ensuring that a sufficient number of cells would be converted to dystrophin-positivity. Our studies also indicate that this approach should lead to stable expression of the gene. We have shown that the intravascular injection of naked plasmid DNA (pDNA) into the femoral artery of rats leads to very high foreign gene expression in skeletal muscle throughout the leg and without damaging the muscle. Previous experience with naked DNA and adenoviral vectors showed that the gene transfer efficiency decreased substantially when going from the young mouse, to adult mouse and then adult rat. The fact that we can achieve very efficient expression in an adult rat is quite encouraging. The objective of this proposal is to extend this approach to larger animals, non-human primates and the dog and its associated Duchenne model. If successful in primates and dogs, a human clinical trial in patients with Duchenne muscular dystrophy could begin in the near future. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen
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Project Title: GENERAL CLINICAL RESEARCH CENTER Principal Investigator & Institution: Goldsmith, Lowell A. Professor and Chair; None; University of Rochester Orpa - Rc Box 270140 Rochester, NY 14627 Timing: Fiscal Year 2001; Project Start 01-OCT-1974; Project End 30-NOV-2000 Summary: Since 1960, the University of Rochester GCRC has fostered productive, hypothesis-driven, investigator-initiated clinical research. During the last 5 years, center investigators have published more than 200 peer- reviewed research publications focusing on such diverse areas as Infectious Diseases, Environmental Medicine, Geriatrics, Dermatology, Neuromuscular Diseases, Cardiology, Parkinson's Disease, Endocrinology and Metabolism, and Neonatology. Moreover, usage has grown and initiatives in genetics and gene therapy have been attracted to the Center. The present application contains diverse projects from medical school and nursing school faculty. The proposed projects expand ongoing studies in AIDS, aging, environmental exposures, muscular dystrophy, Amyotropic Lateral Sclerosis (ALS), Parkinson's Disease, diabetes, obesity, oncology, neonatal respiratory distress syndrome, bronchopulmonary dysplasia, and the epidemiology of pediatric infectious diseases. New initiatives include protocols to study genetics, utilize gene therapy in the treatment of ovarian cancer, and better understand posthepatectomy liver regeneration. The University of Rochester Investigators are well-funded, making the GCRC a productive and fertile research environment. This proposal also includes a major series of new educational initiatives which should particularly assist young investigators and attract new investigators. Supporting the proposed protocols are facilities that include: The Core Laboratory (RIA, HPLC, Mass Spectroscopy, and Body Composition); CDMAS, Nutrition, and a stable, well-trained, research nursing staff: In addition, the Rochester Area Pepper Center (Geriatrics), the Cancer Center, and the AIDS center will continue to integrate their programs with the GCRC to optimize realization of the full clinical research potential of the University environment. Thus, the Rochester GCRC supports a cadre of proven, productive and innovative researchers that should continue to make major contributions to our understanding of clinical disorders. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen
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Project Title: GENETIC ANALYSIS OF SYNAPSE FORMATION AND FUNCTION Principal Investigator & Institution: Broadie, Kendal S. Professor of Biological Sciences; Biology; University of Utah 200 S University St Salt Lake City, UT 84112 Timing: Fiscal Year 2001; Project Start 01-AUG-1997; Project End 31-AUG-2002 Summary: Movement, behavior and higher brain function all depend upon the ability of neurons to communicate via specialized intercellular junctions called synapses. Many forms of neurological disease affect the synapse both in the central nervous system (CNS: e.g. Parkinson's Disease, Epilepsy) and at the neuromuscular junction (NMJ: e.g. Myasthenia and several types of Muscular Dystrophy). Moreover, synapse regeneration is central to neural repair following brain trauma (e.g. stroke) or injury. (e.g. loss of a limb). Our objective is the systematic dissection of the function and organization of individual components of the synapse. Such an analysis requires methods to identify specific synaptic proteins as well as methods to assay their function. Drosophila offers unique possibilities for a rigorous analysis of this kind: sophisticated genetic methods can be combined with refined functional and anatomical assays to study an assessable synapse, the NMJ. This proposal has two specific aims: 1) to identify new proteins involved in presynaptic function and development by performing genetic screens and, 2) to characterize the phenotype of existing mutants in order to define their role in
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presynaptic mechanisms. For the first objective, screens will be conducted by identifying mutants with defective NMJs among uncoordinated lethal mutations on the third chromosome (40% of the genome). Our aim is to saturate the third chromosome for synapse dysfunction mutants, order these mutants into functional classes and initiate a molecular characterization of the isolated genes. For the second objective, we will focus on the phenotypic characterization of known synaptic mutants isolated via reverse genetic techniques. This work will include the functional and anatomical characterization of mutants in Neurexin, a Rab3A-interacting gene and double-mutant combinations of presynaptic genes. Both forward and reverse genetic approaches demand assays that measure different aspects of defective synaptic function in clear and quantifiable ways. We have developed assays to monitor the developing embryonic NMJ either in vivo or in culture using a combination of patch-clamp electrophysiology, gross morphology and ultrastructural analyses. The intention of this proposal is to bring these approaches together in order to increase substantially the number of genes known to be required at the synapse. In the long term, we intend to mutate the entire genome to identify and describe the genetic and molecular pathways directing the construction and working of the synapse. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •
Project Title: GENETIC AND MOLECULAR ANALYSES OF MUTATIONS Principal Investigator & Institution: Brilliant, Murray H. Professor of Mammalian Genetics; Pediatrics; University of Arizona P O Box 3308 Tucson, AZ 857223308 Timing: Fiscal Year 2001; Project Start 01-JUL-1989; Project End 30-JUN-2003 Summary: (Adapted from investigator's abstract) This is a competitive renewal for an RO1 in its third funding cycle that requests five years of support to identify and analyze genes uncovered by genetic rearrangements that affect the p gene. Previous work by the applicant has defined two complementation groups -- runty/jerky/sterile (rjs) and cleft palate -- which lie proximal and distal to p, respectively. In the previous funding cycle, the applicant identified a very strong candidate for the rjs gene, demonstrated that deletion of the Gabrb3 gene was responsible for cleft palate, and, in addition, described an inversion allele, p100H, that disrupts the Sox6 gene and causes an unusual muscle disease reminiscent of Emery-Dreyfuss muscular dystrophy. The current application proposes to extend work in all three areas. The molecular pathogenesis of rjs deficiency will be investigated by further characterization of gene and protein expression, by identification of interacting proteins, and, in collaboration with others, biochemical and/or cell biologic assays of rjs domains that may function in protein ubiquitination and guanine nucleotide exchange. In addition, a loxP-flanked rjs allele will be created to investigate whether the pleiotropic phenotype caused by rjs deficiency reflects the sum of several tissue-specific defects. Preliminary studies suggest that cleft palate caused by deficiency for Gabrb3 reflects a requirement outside the central nervous system, pointing to a potentially novel role for GABA signaling during palate morphogenesis. These data will be confirmed by further studies of a Gabrb3 transgene controlled by the neuron-specific enolase promoter. In addition, the sites of Gabrb3 gene and protein expression, and GABA binding sites, will be characterized in non-neuronal tissues with special attention to the developing palate. The pathogenesis of muscle disease caused by the p100H mutation will be investigated by further characterization of a newly recognized Sox6 isoform highly expressed in muscle, by development of myoblast/myocyte cell culture systems from mutant animals, and by Sox6 gene rescue experiments in vivo and/or in vitro. In addition, differential display, cDNA subtraction,
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and/or gene expression profiling will be used to compare mutant and non-mutant tissues in an attempt to identify Sox6 targets. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •
Project Title: GENETIC MECHANISMS OF MUSCULAR DYSTROPHY IN MICE Principal Investigator & Institution: Cox, Gregory A. Associate Staff Scientist; Jackson Laboratory 600 Main St Bar Harbor, ME 04609 Timing: Fiscal Year 2003; Project Start 01-JUN-2003; Project End 31-MAY-2008 Summary: (provided by applicant): The broad long term goals of this research are to better understand the molecular genetic mechanisms underlying neuromuscular disease using a novel mouse mutation as an experimental model. Muscular dystrophies include a diverse group of genetically heterogeneous disorders characterized by progressive muscle weakness and wasting that leads to severe disability and often premature death. There is a need to learn more about pathogenesis of the diseases and translate this knowledge into effective treatments. Toward this goal, we propose to study the mechanism of pathogenesis in the mdm mutant mouse, a novel model of progressive muscular dystrophy that functionally links the enormous Titin (Ttn) gene to the limbgirdle muscular dystrophy type 2A (LGMD2A) cysteine protease calpain 3 (Capn3). We have genetically mapped and identified the mdm mutation as a complex rearrangement that results in a small in-frame deletion within a putative CAPN3-interacting domain of TTN. The mdm mouse may also serve as a genetic model for human tibial muscular dystrophy (TMD) which maps to the TTN locus at 2q31. This is the first demonstration that mutations in Ttn are associated with muscular dystrophy and provides a novel animal model to test for functional interactions between these two disease genes. The steps we will take to elucidate the roles of titin and calpain 3 in muscle cell degeneration will be to 1) test the hypothesis that calpain 3 interactions with titin are disrupted by the mdm mutation, 2) test the alternate hypotheses that the progressive mdm muscular dystrophy is due to either reduced CAPN3 levels or aberrant activation of the CAPN3 protease, and 3) generate a Ttn-null allele by gene targeting and an allelic series of muscular dystrophy mutations at the Ttn locus using a sensitized ENU mutagenesis screen. Thus, the mdm mutant mouse provides a unique tool for understanding molecular pathways causing muscular dystrophy and may reveal entry points in which to intervene in the disease process. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen
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Project Title: GENETIC MODIFICATION OF STRIATED MUSCLES DURING AGING Principal Investigator & Institution: Metzger, Joseph M. Professor; Human Genetics; University of Michigan at Ann Arbor 3003 South State, Room 1040 Ann Arbor, MI 481091274 Timing: Fiscal Year 2001; Project Start 01-MAY-1998; Project End 30-APR-2003 Summary: This program project application is designed to explore mechanisms of genetic diseases that affect striated muscle, how these diseases are affected by the normal aging process, and it also seeks to develop gene therapy approaches for treating these diseases. The applicants are a diverse and broad based group of researchers with interests in ageing, muscle structure-function relationships, genetic muscle diseases, and gene therapy. The affiliated projects focus on cardiac and skeletal muscle disease and bring together the fields of gerontology, physiology, molecular biology, and genetics. Project 1 seeks to develop a new class of adenoviral vectors that lacks all viral genes and
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that can transfer large genes into striated muscle of young and old animals. Project 2 aims to develop a better understanding of the role of the dystrophin associated protein complex in striated muscle, how mutations in genes that encode the proteins of this complex lead to muscular dystrophies (CDs), and how normal ageing contributes to the pathology of the MDs. Project 3 explores hypertrophic cardiomyopathies, and aims to develop adenoviral vector mediated gene transfer to the heart as a mechanism to correct inherited cardiac diseases at different stages of disease progression. These projects will be supported by four Core Laboratories. Core 1 is an administrative core to coordinate the separate projects. Core 2 is a Viral Vector Core to provide large scale growth of adenoviral vectors and assistance with their use. Core 3 is an Animal Models/Immunology Core that will house the animals for these studies, provide veterinary care and assistance with protocols, and which will also provide detailed immunological assays to study immune responses to adenoviral vector transfer. Core 45 us a Contractility Core that will measure changes in muscle contractile properties during ageing of normal and diseased muscle and following adenoviral based gene transfer to striated muscles. These projects will lead to a greater understanding of muscle diseases and ageing, and will contribute to the development of therapies for inherited diseases of skeletal and cardiac muscle. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •
Project Title: GENETIC REGULATION OF SKELETAL MUSCLE REPAIR Principal Investigator & Institution: Rudnicki, Michael A. Associate Professor; Ottawa Hospital Research Institute Ottawa, Timing: Fiscal Year 2001; Project Start 15-JUL-1996; Project End 31-AUG-2004 Summary: To test for a role for MyoD in muscle regeneration, we interbred MyoD mutant mice with mdx mice. The mdx mice lack dystrophin, but unlike humans do not develop extensive dystrophic damage. By contrast, mdx:MyoD-/-mice display severe dystrophic changes and cardiomyopathy that lead to premature death around one year of age. We propose to further characterize skeletal and cardiac muscle of mdx:MyoD-/mice by extensive morphometric, immunohistological, physiological, and molecular analyses. Satellite cells are a distinct lineage of myogenic cells that arise late in development. To investigate the ontogeny of satellite cells, chimeric mice will be generated using Myf-5-/-:MyoD-/- embryonic stem (ES) cells constitutively expressing lacZ. To investigate the role of the Myf-5 in satellite cell self-renewal and activation, we will investigate muscle regeneration in mice carrying MyoD or myogenin knocked into the Myf-5 allele. In addition, a Cre-inducible loss-of function mutation will be knocked into the endogenous Myf-5 allele and Cre-recombinase will be expressed from the endogenous MyoD gene, or by infection with Cre-expressing adenovirus. The ETSdomain transcription factor PEA3 is rapidly induced following muscle damage and PEA3 expression stimulates myoblast differentiation and is positively correlated with metastatic potential. We propose to characterize muscle regeneration and myoblast differentiation in PEA3-/- mice that we have generated. Many lines of evidence support the assertion that cell cycle control and myogenic factor activity is coupled via a mechanism that regulates the switch from proliferation to differentiation. We have generated null mutations in members of the retinoblastoma-family of cell cycle control genes. We will analyze muscle regeneration in vivo and myogenic cell growth and differentiation in vitro to elucidate the role of cell cycle control in myogenic stem cell function. Understanding how regulatory genes control the growth and repair of skeletal muscle is highly relevant to understanding the regenerative processes that occur in patients with various muscular dystrophy's. We believe that our proposed studies will
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provide novel insights into the biology of muscle regeneration. Potentially, such insights may lead to new modalities of therapeutic intervention. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •
Project Title: GENETIC STUDIES OF PTS AND FAMILIES W INHERITED CARDIOVA Principal Investigator & Institution: Mcnally, Beth; University of Chicago 5801 S Ellis Ave Chicago, IL 60637 Timing: Fiscal Year 2001 Summary: This abstract is not available. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen
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Project Title: GENETICS AND BIOCHEMISTRY OF A MURINE RETROPOSON Principal Investigator & Institution: Martin, Sandra L. Professor; Cellular & Structural Biology; University of Colorado Hlth Sciences Ctr P.O. Box 6508, Grants and Contracts Aurora, CO 800450508 Timing: Fiscal Year 2001; Project Start 01-JUL-1988; Project End 30-JUN-2002 Summary: LINE-1 (long interspersed repeated sequence one, or L1) is a major dynamic force in the mammalian genome. Retrotransposition deposits the progeny of L1 throughout the genome, sometimes leading to gene disruption, modified expression of adjacent genes, and/or transduction of neighboring DNA. In addition, L1, as interspersed, repetitive DNA, provides a substrate for homologous recombination of mispaired sequences, leading to gene duplication, deletion, chromosome translocation and, potentially, exon shuffling. All of these dynamic events can lead to disease; in fact, LINE-1 insertional mutagenesis has been found to be responsible for hemophilia and muscular dystrophy, as well as breast and colon cancer in humans. Thus, it is extremely important to understand the details of the intermediates involved in retrotransposition and the mechanisms used to control their expression and movement in vivo. If the normal control mechanisms of L1 expression and retrotransposition become deranged and during development (gametogenesis or early embryogenesis) or in somatic cells in response to environmental insults, movement and rearrangement of L1 sequences could be instrumental in the generation of genetic diseases, birth defects and cancer. LINE-1 retrotransposition begins with transcription of a full-length, sense-strand L1 RNA and requires two L1-encoded polypeptides. These proteins probably also catalyze the reverse transcription and integration of SINEs (short interspersed repeated sequences) and processed pseudogenes, thereby amplifying the effects of LINE-1 in mammalian genome dynamics. Our long-range goal is to understand the retrotransposition process in detail, including the biochemical intermediates involved as well as its control in genetic and evolutionary time. Specifically, the studies proposed here are designed to: 1) Elucidate the role of the L1-encoded ORF1 protein during retrotransposition by characterizing its nucleic acid and protein- protein interaction activities in detail, as well as to test this protein for its ability to promote complementary strand annealing and strand-exchange; 2) Isolate the mouse genomic DNA progenitor of one of the promoters that was acquired by mouse LINE-1 recently in evolutionary time, and; 3) Employ our newly developed transposon tray assay to characterize the types of insertions that occur, as well as determine the frequency of endogenous L1 and L1-mediated retrotransposition events in the presence and absence of external agents. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen
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Project Title: GENTAMICIN TRIAL IN DUCHENNE AND LIMB GIRDLE DYSTROPHIES Principal Investigator & Institution: Mendell, Jerry R. Neurology; Ohio State University 1800 Cannon Dr, Rm 1210 Columbus, OH 43210 Timing: Fiscal Year 2002; Project Start 15-SEP-2002; Project End 31-JUL-2005 Summary: (provided by applicant): The study will determine if the aminoglycoside, gentamicin, has potential as a therapeutic medication for Duchenne muscular dystrophy (DMD). To fulfill this potential, long-term administration of gentamicin must be safe and improve muscle strength. Ideally, it will also increase dystrophin expression with binding at the muscle membrane. The testing paradigm will be a three-arm, sixmonth, double blind, randomized controlled trial of intravenous (IV) 7.5 mg/kg of gentamicin. Groups 1, 2, and 3 will each have 12 subjects. Group 1 will receive gentamicin every three days, while group 2 will receive drug every seven days. Group 3 subjects receive an IV placebo of 5% dextrose and saline; six subjects infused every three days and six others every seven days. In addition, gentamicin will be used in two shortterm, 14-day studies. If either of these groups responds to the 14-day administration by decreasing serum creative kinase (CK), then they become potential candidates for sixmonth administration. One group of 14-day subjects will have DMD with frameshift mutations. Despite commonly held dogma that aminoglycosides have no effect on this mutation-type, it is important to establish as effect by testing to see if CK drops. A positive outcome potentially reaches more patients, since this is the most common type of DMD gene mutation. Gentamicin will also be used to treat limb girdle muscular dystrophy subjects with stop codon mutations. If the serum CK is lowered, the potential for long-term treatment will be established for these patients. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen
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Project Title: GORDON RESEARCH CONFERENCE ON BASEMENT MEMBRANES Principal Investigator & Institution: Kramer, James M. Professor; Gordon Research Conferences Gordon Res Ctr C/O Univ of Rhode Island Kingston, RI 02881 Timing: Fiscal Year 2002; Project Start 09-JUN-2002; Project End 31-DEC-2002 Summary: (provided by applicant): This application requests partial funding for the support of invited speakers for the 2002 Gordon Conference on Basement Membranes. This is the eleventh in a series of conferences, which have become an international forum for dissemination of new ideas and information about the structure and functions of basement membranes (BMs). These are complex, three dimensional, extracellular structures formed at epithelial mesenchymal interfaces and around mesenchymal cells, with important roles in the organization and function of most tissues and organs, e.g., blood vessels, lung, kidney, skin, peripheral nerves, and muscle. For example, basement membranes regulate the migration and organization of cells in the musculoskeletal system, as well as axons and synapses in the nervous system. Mutations in genes encoding basement membrane components result in severe inherited disorders in humans (e.g., epidermolysis bullosa of skin, congenital muscular dystrophy and associated nerve defects, Alport syndrome of kidney). Acquired defects in basement membranes also contribute to the pathogenesis of diabetic microvascular disease and serve as entry sites for infectious agents, such as leprosy, and for metastatic cancer cells. Traditionally, the conference has attracted scientists from a wide range of fields in basic research, including protein and carbohydrate structure, gene expression, cell and developmental biology, and neurobiology. In addition, it has been attended by clinicians and scientists involved in research and/or treatment of human disorders involving BM
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components of lung, blood vessels, skin, kidney, bone, muscle and immune systems. Basic studies of BM degradation and turnover are also of interest to scientists investigating dynamic processes such as angiogenesis, cancer metastasis, embryo implantation, and involution of the mammary gland and uterus. There has been substantial interest from clinicians and scientists in the pharmaceutical and biotechnology industries studying the roles of BMs in wound healing, angiogenesis, nerve regeneration, inflammation, and tissue repair. The Conference will present a diverse mixture of sessions on the basic science of basement membrane and extracellular matrix (ECM) structure, biosynthesis, assembly, turnover, and functions. Comparative studies of BM function in vertebrates and invertebrates and the roles of BM and ECM in embryonic development will also be incorporated into the program. In addition, emphasis will be given to studies on the genetic analyses of BM and ECM functions, and the generation of animal models of human BM disorders. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •
Project Title: IDENTIFICATION OF NATURAL MESENCHYMAL STEM CELL LIGANDS Principal Investigator & Institution: Larocca, David J.; Selective Genetics, Inc. 11588 Sorrento Valley Rd, Ste 21 San Diego, CA 921211336 Timing: Fiscal Year 2003; Project Start 10-SEP-2003; Project End 28-FEB-2004 Summary: (provided by applicant): Adult stem cells from bone marrow have the potential to provide a vast resource for regenerative medicine which would allow the replacement of injured or defective cells and tissues. While it is known that mesenchymal stem cell (MSC) populations from bone marrow have the potential to differentiate into many different cell types including bone, cartilage, fat and possibly others, there is little understanding of the molecular basis that characterizes the different progenitor cells. Also lacking is a clear understanding of the factors that regulate their growth and differentiation. The purpose of this grant proposal is to identify and characterize natural ligands from within the human genome that target cell surface receptors on mesenchymal stem cells. Phage display libraries will be constructed using novel cDNA display methods and selected on MSCs to identify natural peptide ligands that bind and internalize into MSCs. Novel selection methods will be used to select internalizing ligands with greater sensitivity than currently available techniques. Selected ligands will be characterized for specificity and function. Near term, these ligands will serve as targeting ligands for the introduction of genes and drugs into mesenchymal stem cells that would augment their use in tissue engineering and treatment of disease. Moreover, it is likely that certain ligands will be useful as biological drugs that can be used commercially to either maintain stem cell populations in an undifferentiated state, or to stimulate their differentiation to specific cell types. In the long term, an understanding of these natural ligands and their receptors on bone marrow stem cells will allow rational design of drug treatments that augment the bodies own mechanism for tissue repair due to injury (i.e. wound healing, bone and cartilage growth), or due to cell loss from diseases like diabetes, Parkinson's disease, and muscular dystrophy. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen
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Project Title: IMPROVED DIAGNOSIS OF THE MUSCULAR DYSTROPHIES Principal Investigator & Institution: Hoffman, Eric P. Director; Children's Research Institute Washington, D.C., DC 20010
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Timing: Fiscal Year 2001; Project Start 01-JAN-1991; Project End 30-NOV-2003 Summary: This application is the second competitive renewal of this "Improved Diagnostics of the Muscular Dystrophies" grant. During the first award, we showed that primary dystrophinopathies caused the majority of cases of muscular dystrophy, specifically about 80% of male dystrophy patients, and 10% of female dystrophy patients. During the tenure of the second award period (Dec 95-present), we begin dissecting the cause of muscular dystrophy in patients with normal dystrophin. During the last two years, we have investigated muscular dystrophies caused by alphasarcoglycan, beta-sarcoglycan, gamma-sarcoglycan, delta-sarcoglycan, merosin, integrin-alpha7, and calpain III. Despite the advances in our understanding of the molecular basis of muscular dystrophy made by our laboratory and others, we can identify the underlying molecular basis for only about 30% of autosomal recessive cases; 70% of patients with normal dystrophin can not be assigned a specific molecular diagnosis. Thus, considerable work remains to identify the many genes causing muscular dystrophy, and this is the focus of this competitive renewal. Our laboratory serves as the major referral site for molecular diagnostics of the muscular dystrophies. Through our for gratis analysis of muscle biopsies for primary dystrophinopathies, and more recently sarcoglycanopathies and merosin disorders, we have assembled what is likely the most extensive tissue-bank of frozen muscle tissue and clinical records of muscular dystrophy patients in the world. 3,049 flash-frozen muscle biopsies from muscular dystrophy patients have been received by the laboratory and fully characterized by the laboratory for dystrophin expression, histopathology, and, in hundreds of cases, gene mutations. It is these well-characterized muscle biopsy specimens which form the starting material for the molecular studies proposed in this renewal application. The goals of this current application are: 1. To continue our successful candidate gene analyses in our large cohort of muscular dystrophy patients; 2. To use the newly emerging GeneChip system (Affymetrix) to determine the changes in gene expression resulting from mutations in specific muscular dystrophy genes as a means to understanding disease progression and pathophysiology; and 3. To use the Gene Chips to identify novel muscular dystrophy genes through specific changes in gene expression. The proposed research will lead to improved understand the etiology of muscular dystrophies and improved diagnosis of these disorders. The results will enable genetic counseling of patients and their families, and should facilitate efforts directed towards rational therapies. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •
Project Title: INTRACELLULAR ASSEMBLY AND TARGETING OF SIGNALING MOLECULES IN HEART FAILURE Principal Investigator & Institution: Michel, Thomas M. Chief of Cardiology; Brigham and Women's Hospital 75 Francis Street Boston, MA 02115 Timing: Fiscal Year 2001 Summary: In heart failure, the molecular regulation of intracellular and intercellular myocardial signaling pathways is often profoundly perturbed. Many signaling proteins in cardiac myocytes, including G proteins, G protein- coupled receptors, calciumregulatory proteins, and nitric oxide synthase- are localized in sarcolemmal caveolae. Cardiac myocyte caveolae represent highly specialized invaginations of the sarcolemma, and form the T-tubular system that organizes and regulates sarcomere calcium delivery. Myocyte caveolae contain the protein caveolin-3, a transmembrane protein that serves a scaffold for the localization of many signaling proteins. During the initial funding period of this SCOR, we discovered that the endothelial isoform of nitric oxide synthase
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(eNOS) is expressed in cardiac myocytes and that its activity is regulated by its interactions with caveolin-3. The central hypothesis to be tested in these studies is that nitric oxide synthase and other key caveolae-targeted signaling proteins are aberrantly regulated in heart failure. In Aim 1, we will determine the composition the composition and regulation of cardiac myocyte caveolae in normal and failing hearts, and characterize the signaling proteins present in cardiac myocyte caveolae following receptor activation in vivo and in vitro. We will perform cellular imaging of caveolaetargeted signaling proteins using confocal laser microscopy, and identify the intracellular sites of NO synthesis in cardiac myocytes using the newly developed fluorescent dye, diaminofluorescein. Both eNOS and iNOS will be studied in this context, analysis of iNOS localization may provide new information on the role of NO in myocardial depression in systemic sepsis. These cellular imaging studies of caveolae constituents will be analyzed in the murine heart failure models being studied by other SCOR investigators. In Aim 2, we will conduct fluorescence resonance energy transfer experiments to explore interactions between cardiac myocyte-derived NO, caveolin and Ca++-binding regulatory proteins in T-tubules. In Aim 3, we will explore the role of caveolin-3 in regulation of NO-dependent signaling pathways in the myocardium; these studies may yield insights into the pathophysiology of cardiomyopathies associated with muscular dystrophy syndromes. In Aim 4, we will characterize the electrophysiological phenotype of eNOS/null mice using programmed electrical stimulation and drug infusions, as well as ambulatory EGG monitoring in eNOS/null mice, including heart rate variability analysis. Since we have shown that eNOS importantly modulates the autonomic control of myocyte beating rate in vitro, the in vivo studies in Aim 4 may provide new insights into the molecular mechanisms of sudden cardiac death in heart failure. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •
Project Title: INVESTIGATION OF A DYSTROGLYCAN COMPLEX IN EPIDERMIS Principal Investigator & Institution: Santas, Amy J.; Fred Hutchinson Cancer Research Center Box 19024, 1100 Fairview Ave N Seattle, WA 98109 Timing: Fiscal Year 2003; Project Start 01-DEC-2003 Summary: (provided by applicant): The main objective of this proposal is to compare two epidermal cell adhesion complexes, a dystroglycan-containing complex (DGC) and the hemidesmosomes. Hemidesmosomes and the DGC are transmembrane receptor complexes that serve to connect the extracellular matrix and the cytoskeleton and are essential to maintain integrity of epidermis and muscle, respectively Severe blistering results from genetic defects in hemidesmosome components while muscular dystrophy develops from defects in DGC components In our preliminary studies, two components of DGC (utrophin & Beta-dystroglycan) were identified in epidermal tissue and uncultured primary keratinocytes Upon culturing, neither components of DGC nor mature hemidesmosomes were detectable This proposal will delineate the composition of the epidermal DGC and its physical and functional relationship with hemidesmosomes in epidermis and in an in vitro system to be developed. Ultrastructural association of DGC and hemidesmosomes will be examined using immunoelectron microscopy while functional interrelatedness will be examined by staining for DGC in tissues that do not form hemidesmosomes Loss of hemidesmosomes or decrease in dystroglycan expression directly correlates with poor prognosis in epithelial cell based cancers The long term goal of this research is to identify the role of the complex(es) in cancer as to better understand the progression and targets of these cancers.
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Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •
Project Title: ION CHANNELS AND CHEMICALS CONTROLLING SYNAPSE STABILITY Principal Investigator & Institution: Mcardle, Joseph J. Professor; Pharmacology and Physiology; Univ of Med/Dent Nj Newark Newark, NJ 07103 Timing: Fiscal Year 2003; Project Start 01-FEB-2003; Project End 31-JAN-2007 Summary: (provided by applicant): Synapses are the major locus of information transfer within our brain as well as the target of numerous pathologies which can afflict humans from development in utero to death. Therefore, major research effort is given to understanding synapse formation and stabilization throughout life. The scientific literature concerning synapses is rich with discovery of fundamental principles derived from study of the neuromuscular junction (NMJ). In particular, proteins responsible for NMJ function, formation, and stability are relatively well understood. Nevertheless, fundamental questions remain concerning interactions between these proteins. An important experimental model suggests that heterogeneous activity of AChRs influences stability of the adult NMJ. This proposal modifies and extends that model to the developing NMJ where co-expression of immature gamma and mature epsilon AChRs during the critical phase of NMJ maturation produces heterogeneity of end-plate activity. Our model suggests that end-plate areas rich in epsilon AChR mediate Ca 2+ influx which activates co-localized nitric oxide synthase (nNOS). The nitric oxide (NO) produced diffuses to nerve terminals competing for the motor end-plate. New preliminary data suggest that NO enhances Ca2+ currents and transmitter release at adult motor nerve terminals. Thus, developing nerve terminals activating end-plate loci containing the epsilon AChR may be functionally enhanced and nurtured via NO activation of presynaptic guanylyl cyclase. In contrast, NO may repress function and stability of competing nerve terminals activating epsilon AChR poor end-plate foci. The mouse Triangularis sterni (TS) preparation facilitates exact testing of our model. Our preliminary data show that the TS preparation isolated from neonatal mice allows simultaneous recording of nerve terminal currents and post-synaptic events at endplates receiving innervation from terminals originating in distinct nerve trunks. This allows unprecedented study of the function of, and NO-mediated cross talk between, mammalian nerve terminals competing for a postsynaptic target. The availability of epsilon subunit and nNOS knock out mice, as well as the epsilon AChR selective ligand Waglerin- 1 further strengthen experiments proposed to test our model. Additional novel preliminary data suggest that insulin, an activator of the neuronal K-ATP channel, suppresses quantal release of Ach at the adult NMJ. Therefore, a second goal of this proposal is to discover if insulin, as well as glucose, effects the function, and eventual stability, of nerve terminals competing at the developing NMJ. This will be explored in a non-obese mouse model of type I diabetes. Overall, this research is clinically relevant since NO signaling cascades are significantly altered in Duchenne muscular dystrophy as well as animal models of stroke. In addition, altered function of the epsilon AChR is responsible for NMJ pathology associated with slow channel congenital myasthenic syndrome. The proposed evaluation of insulin effects is novel and will enhance understanding of the neurologic consequence of adult and juvenile forms of diabetes. The knowledge gained from this research will enlighten future molecular approaches to treating pathologies which afflict children and adults. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen
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Project Title: LAMININ ALPHA 2 IN TISSUE REGENERATION Principal Investigator & Institution: Engvall, Eva S. Associate Scientific Director; Burnham Institute 10901 N Torrey Pines Rd San Diego, CA 92037 Timing: Fiscal Year 2001; Project Start 01-MAR-1996; Project End 28-FEB-2005 Summary: (Adapted from applicant's abstract) Tissue regeneration and repair are critical to longevity. Insufficient regeneration of muscle and nerve is a significant cause of morbidity in patients with muscular dystrophy and other muscle and nerve diseases and in the aging individual. The laminin subunit a2 is prominently expressed in striated muscle and peripheral nerve, and mutations in the lama2 gene cause a severe form of muscular dystrophy in humans (merosin-deficient congenital muscular dystrophy, MCMD) and mice. A mouse model for human MCMD was generated by disrupting the lama2 gene with the lacZ reporter gene. Homozygous mutant mice develop muscular dystrophy and peripheral neuropathy after birth. Absence of laminin a2 does not significantly affect myogenesis, but the differentiated laminin a2-deficient muscle are highly susceptible to injury upon contraction. Most important, in contrast to the apparent normal development, regeneration is severely compromised in the absence of laminin a2. It is proposed to use in vivo and in vitro models to analyze development and regeneration of skeletal muscle and peripheral nerve to determine which steps in the regeneration process are dependent on laminin a2. The regeneration-promoting effects of laminin a2 will be analyzed in transgenic mice with tissue-specific overexpression of a human LAMA2 transgene. To analyze the molecular pathways responsible for maturation and survival of skeletal muscle and Schwann cells, integrin and dystroglycan signaling pathways will be characterized by using the yeast 2-hybrid screening and affinity chromatography in combination with peptide mass mapping. The proposed research will result in new knowledge regarding important molecular mechanisms of muscle and nerve function and may help in devising new strategies for treatment of degenerative diseases of muscle and nerve based on promoting regeneration. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen
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Project Title: LAMININ INDUCED MEMBRANE COMPLEXES IN MUSCLE AND NERVE Principal Investigator & Institution: Yurchenco, Peter D. Professor; Pathology and Lab Medicine; Univ of Med/Dent Nj-R W Johnson Med Sch Robert Wood Johnson Medical Sch Piscataway, NJ 08854 Timing: Fiscal Year 2001; Project Start 01-APR-1999; Project End 31-MAR-2004 Summary: Null and domain-activating mutations of the basement membrane laminin alpha2 (merosin) subunit are reported to cause human and murine congenital muscular dystrophies and peripheral nerve defects. Our laboratory is studying the inductive role of laminins on myotubes and Schwann cells, and preliminary data reveal that alpha2laminin and its alpha1-laminin homologue binding to myotube cell surfaces through laminin G protein-specific integrin and alpha-dystroglycan receptors. These cruciform laminins self-assemble into polymers through their short arms, cluster the two receptors into polygonal complexes through their anchored long arm, and induce the formation of a vinculin-rich cortical cytoskeletal lattice that mirrors the organization of laminin and its receptors. We also have evidence that alpha2-laminin bearing the dy/2.1 dystrophic deletion is defective in its ability to self-assemble, to aggregate its receptors, and to assemble this cortical architecture. Based on these and other data, our working hypothesis is that laminin-2 plays a major role in driving the assembly of the myotube
58 Muscular Dystrophy
and Schwann cell cytoskeleton, a process mediated by its ability to bind to the cell surface, to polymerize, and to activate and reorganize its cognate receptors. This receptor and cytoskeleton reorganization, resulting from a dynamic integration of laminin activities, may be important for the development, maintenance and stabilization of muscle and nerve sheaths. Furthermore, a loss of one or more of these functions may cause muscular dystrophies with neuropathies. We propose to explore this concept in the following specific aims: I. Laminin-Myotube and Laminin-Schwann Cell interactions: We will study the composition, architecture, and sequential assembly of laminin-induced receptor-cytoskeletal complexes in normal and receptor-deficient myotubes and Schwann cells. II. Structure and function of Recombinant alpha2Laminins Bearing Dystrophic Mutations: We will prepare and evaluate the structure and function of recombinant laminins bearing dystrophic alpha2-subunit mutations with respect to their structure, domain stability, self-assembly, and receptor activities. III. Dystrophic Recombinant Laminin Induction of Receptor-Cytoskeletal Complexes: We plan to study engineered laminins with respect to their ability to induce membrane cytoskeletal networks in myotubes and Schwann cells. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •
Project Title: LAMININ RECEPTORS AND SIGNALS IN SCHWANN CELLS Principal Investigator & Institution: Feltri, Maria L.; Istituto Scientifico San Raffaele Via Olgettina 60 Milano, Timing: Fiscal Year 2003; Project Start 01-JUL-2003; Project End 30-JUN-2007 Summary: (provided by applicant): Laminin is important for peripheral nerve development and myelination. Laminin mutants cause a dysmyelinating neuropathy in man (congenital muscular dystrophy, CMD) and mouse (dystrophic, dy) that manifests both impaired Schwann cell-axon interactions and altered myelination. The molecules that transduce laminin effects in Schwann cells, and the pathomechanisms of laminin mutants remain largely unknown. We have identified several laminin receptors in myelin-forming Schwann cells and shown that they are differentially expressed across peripheral nerve development, suggesting that they subserve differential roles. Our preliminary genetic analysis confirms this notion: Beta1integrin is required for establishing proper Schwann cell-axon relationships prior to birth, whereas dystroglycan is necessary for normal myelination after birth. The Beta1and dystroglycan-null morphological phenotypes suggest that these receptors normally link laminin to cytoskeletal rearrangements in Schwann cells. The overall goal of this proposal is to expand what is known of the molecular basis of laminin-cytoskeletal linkage in Schwann cells. We have produced or collected an unique group of conditional alleles and Cre transgenes that will allow us to disrupt singly or multiply all known major laminin receptors in Schwann cells of transgenic mice. Furthermore, imaging and biochemical analysis of Beta1integrin-null Schwann cells will elucidate how Beta1 directs cytoskeletal rearrangements. Proteomic analysis of Beta1integrin-null Schwann cell/neuron explants will identify candidate signal molecules that link laminin to the cytoskeletal alterations required for axonal interactions. This comprehensive approach will establish the role of the different laminin receptors in peripheral nerve, thereby clarifying the pathogenesis of CMD and dy mutations. The information produced by these experiments will collectively form a basis for developing treatment strategies of CMD and other hereditary neuropathies, and to promote nerve regeneration and remyelination in all neuropathies. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen
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Project Title: LIMB GIRDLE MUSCULAR DYSTROPHY GENE THERAPY Principal Investigator & Institution: Campbell, Kevin P.; University of Iowa Iowa City, IA 52242 Timing: Fiscal Year 2001 Summary: Autosomal recessive limb-girdle muscular dystrophy (AR-LGMD) refers to a number of genetically and clinically heterogenous neuromuscular disorders that affect mainly skeletal muscle. Over the last few years, it has become clear that a number of genes encoding protein components of the sarcoglycan complex are responsible for several forms of AR-LGMDs. The sarcoglycans are expressed at the sarcolemma of muscle fibers and, along with other proteins, constitute the dystrophin-glycoprotein complex (DGC). These proteins are believed to play a role in maintaining the normal architecture of the muscle cell membrane by constituting a link between the subsarcolemmal cytoskeleton and the extracellular matrix. In particular, we have shown that alpha-sarcoglycan, a 50 kDa component of the DGC, is a deficient in skeletal muscle from patients having limb- girdle muscular dystrophy type 2D, and that the expression of all the other sarcoglycan proteins is also strongly reduced in muscle from these patients. Although these findings constitute great progress in our understanding of the genetic basis for AR-LGMDs, there have been no improvements in the treatment of these invalidating diseases. The long-term goal of this research proposal is the development of a gene transfer strategy for AR-LGMDs. We recently generated an animal model for LGMD2D by disrupting the alpha-sarcoglycan gene in mice and preliminary analyses of homozygous mutant mice indicate that their skeletal muscle displays a dystrophic phenotype, as expected, thus providing a valuable animal mode for LGMD2D. The overall objective of this pilot project is to develop a virally-mediated gene transfer of alpha-sarcoglycan and to investigate its therapeutic potential in alphasarcoglycan deficient mice. Our first aim will be the construction of recombinant adenovirus and adeno-associated virus vectors containing the human alpha-sarcoglycan deficient mice. Our first aim will be the construction of recombinant adenovirus and adeno-associated virus vectors containing the human alpha- sarcoglycan cDNA. These vectors will first be tested for their ability to induce expression of alpha-sarcoglycan, both in cultured myoblasts and myotubes. We will then proceed to in vivo experiments designed to test the following hypotheses: i) direct intra-muscular injections of adenoviral- based vectors containing the alpha-sarcoglycan cDNA will efficiently allow expression of the protein and restoration of the DGC in of skeletal muscle of mutant mice (Aim 2) and ii) gene transfer of alpha-sarcoglycan will support functional restoration of muscle fibers in these mice (Aim 3). Overall, the experiments outlined in our proposal will yield new information about alpha-sarcoglycan and the potential for virally-mediated alpha-sarcoglycan gene transfer in mutant mice. In addition, our findings should constitute a foundation for future investigations directed towards developing gene therapy for LGMD2D patients. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen
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Project Title: LLAMA-DERIVED PHAGE DISPLAY ANTIBODY ARRAYS FOR FSHD Principal Investigator & Institution: Van Der Maarel, Silvere M.; Leiden University 46 Stationsweg Leiden, Timing: Fiscal Year 2001; Project Start 30-SEP-2001; Project End 31-AUG-2004 Summary: (provided by applicant): The aim of this project is to gain insight in the cellular and molecular processes leading to dysfunction of the neuromuscular system in
60 Muscular Dystrophy
FSHD patients by large scale analysis of protein homeostasis in tissues and cell lines of patients and controls. In the past few years, projects have been launched to study deregulation of biological pathways in FSHD on RNA level. These strategies include differential display and RNA profiling experiments on commercial and custom made DNA chips and arrays. Despite their limitations, DNA arrays are now one of the most commonly used and successful methods to determine the molecular and cellular aspects of many acquired and genetic diseases. It is anticipated that also for FSHD, this approach will provide a valuable contribution in understanding its pathology. Nevertheless, protein levels, including the level of modified proteins and the composition of protein complexes are of an order of importance larger to understand FSHD pathophysiology. Consequently there is a need for protein arrays. The llama antibody technology provides a unique opportunity to develop protein arrays. The power of the llama system for this purpose is that this animal makes single (heavy) chain antibodies. Using the genetic information for this single-chain repertoire for the construction of phage-display antibody libraries abolishes the need to combine heavyand light-chains, one of the major drawbacks of conventional phage-display libraries. Moreover, these single-chain antibodies tend to have a very high affinity and stability. It has already been demonstrated that large naive and directed libraries of antibodies can be generated. Experience in cloning, production and isolation of these llama antibodies is available. We propose to generate muscle-specific antibody arrays derived from Llama single-chain phage-display clones. To this end, a Llama will be immunized with human muscle protein homogenates, and after peak response, a phage display library will be constructed. Antibody clones will be selected with a variety of selection procedures (e.g. with recombinant proteins or with muscle homogenates from different species) and arrayed on glass slides. Well characterized single chain antibody arrays will be used to study FSHD pathophysiology on fluorescently labeled protein homogenates of tissues and cell cultures of patients and controls. Evidently, these antibodies can also be used individually for specific immunohistochemical and immunocytochemical studies. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •
Project Title: MANIPULATION OF PRENATAL STEM CELL TRANSPLANT BIOLOGY Principal Investigator & Institution: Merchant, Aziz M.; Children's Hospital of Philadelphia 34Th St and Civic Ctr Blvd Philadelphia, PA 19104 Timing: Fiscal Year 2003; Project Start 01-JUL-2003; Project End 30-JUN-2005 Summary: (provided by applicant): Duchenne's muscular dystrophy results from a genetic deletion that creates dysfunctional dystrophin protein resulting in ongoing muscle damage Injured muscle is replaced with more dysfunctional muscle from defective satellite cells which represent the muscle stem cell pool. In utero mesenchymal stem cell transplantation has been shown to result in site specific differentiation and long-term engraftment of skeletal and cardiomyocytes, however the efficiency of engraftment is very low. The rationale of this proposal is that more efficient stem cell engraftment could be obtained by manipulation of embryologic signals involved in homing and migration of myogenic progenitor cells. These signals include transcription factors, such as Pax7, which have been shown to orchestrate specification of muscle progenitors towards satellite cells and other downstream regulatory factors. My research project will involve two specific aims. Specific aim 1 will assess the molecular and biological effects of forced Pax7 expression in a defined population of multipotent adult progenitor cells (MAPC) with the focus on events involved in myogenic
Studies 61
differentiation. The second specific aim will assess the effect of forced Pax7 expression on homing, engraftment, and differentiation of MAPC after systemic administration in a murine model of in utero stem cell transplantation. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •
Project Title: MECHANISM OF CARDIOMYOPATHY IN SARCOGLYCAN DEFICIENCY Principal Investigator & Institution: Heydemann, Ahlke; Medicine; University of Chicago 5801 S Ellis Ave Chicago, IL 60637 Timing: Fiscal Year 2001; Project Start 15-SEP-2001 Summary: Mutations in sarcoglycan, a dystrophin-associated protein complex, cause cardiomyopathy and muscular dystrophy in humans. Through gene targeting, we have generated mice lacking different sarcoglycan subunits to understand better the mechanism by which the loss of these proteins produces membrane instability and cardiac muscle damage. Gamma-sarcoglycan and delta-sarcoglycan are highly related 35 KD, transmembrane proteins. Mice lacking either these sarcoglycans develop cardiomyopathy and show membrane defects characteristic of those seen in humans with mutations in these genes. Gamma-sarcoglycan is expressed exlusively in cardiac and skeletal muscle, yet mice lacking gamma-sarcoglycan appear to have smooth muscle vascular alterations similar to those seen in mice lacking delta-sarcoglycan. Thus, such defects may be a secondary consequence of the primary loss of sarcoglycan in the cariomyocyte. To investigate this, we will compare mice lacking gamma- or deltasarcoglycan. We will rescue smooth muscle expression of delta-sarcoglycan. We will investigate the role of nitric oxide synthase since unopposed vasoconstriction has been identified as a mediator of abnormal vascular tone in the absence of dystrophin. Lastly, we will study whether cardiomyocyte degeneration produces vascular changes by studying other models of cardiomyopathy. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen
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Project Title: MECHANISMS DIFFERENTIATION
OF
TGF-B
REGULATION
OF
MUSCLE
Principal Investigator & Institution: Liu, Dong; Growth and Development; University of California San Francisco 500 Parnassus Ave San Francisco, CA 94122 Timing: Fiscal Year 2002; Project Start 01-MAR-2002 Summary: (provided by applicant): The overall goal in this proposal is to establish physiologically relevant models about how TGF-Beta signaling through the Smad pathway regulates the terminal differentiation of skeletal muscle cells. The first part of the project aims to characterize the mechanism(s) through which TGF-Beta-activated Smads repress the function of MyoD family of myogenic bHLH transcription factors and inhibit muscle differentiation. Specifically, these experiments will extend our initial finding about a role for Smad3 in repression of muscle-specific transcription by determining the underlying mechanism(s), as well as the contribution of each potential mechanism to the antagonistic effect of TGF-beta during myogenesis. The second aim of this proposal is to evaluate the physical and functional interaction between Smads and MEF2 family of transcription factors, and elucidate the impact of such interaction on myogenic differentiation. Finally, since it is important to extend the role of Smad signaling in myogenesis in vivo, we will determine the consequence of altered Smad3 function to the differentiation of myoblast cells injected to normal skeletal muscle tissues and myofiber regeneration following injury and in muscle dystrophy mouse models.
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Our study on the myogenic regulatory function of Smads will provide new insights on how TGF-beta and peptide growth factors in general, regulate mesenchymal cell differentiation. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •
Project Title: MENTORED DEVELOPMENT
PATIENT
ORIENTED
RESEARCH
CAREER
Principal Investigator & Institution: Escolar, Diana M. Associate Professor of Neurology & Pedia; Children's Research Institute Washington, D.C., DC 20010 Timing: Fiscal Year 2001; Project Start 10-AUG-2001; Project End 31-JUL-2006 Summary: (provided by applicant): The applicant is a neurologist and has extensive clinical experience in pediatric and adult neuromuscular diseases. This award will allow her to obtain the training and mentoring to become an independent clinical investigator focusing on neuromuscular disorders. The educational plan includes didactic courses covering epidemiology, statistics, clinical trial design and health policies. DMD is a relatively common fatal genetic disease in children, with equal incidence throughout the world. The goal of this research is to conduct therapeutic human clinical trials with chemicals shown to improve muscle strength in the mdx. The aims of the proposed research plan are: 1) to conduct a double-blind, placebo-controlled, three-arm clinical trial of creatine and L-glutamine in patients with DMD and to assess the effect of these compounds on muscle strength as measured by manual muscle testing (MMT), quantitative muscle testing (QMT) and other functional measurements. Aim 2 is to conduct a double-blind, placebo- controlled clinical trial of coenzyme Q10 (CoQ10) in patients with DMD to assess its effects on: a) muscle strength, measured by QMT, compound Medical Research Council (MRC) score and functional measures; b) exercise capacity, to be measured by a fatigability protocol; and c) quality of life, to be measures by the Child Health Questionnaire. Aim 3 is to validate the specificity of the pediatric QMT system measuring maximal voluntary isometric contraction sequentially in children with DMD. The studies will be conducted at Pediatric Clinical Research Center (PCRC) at the Children's National Medical Center (CNMC), satellite to Georgetown General Clinical Research Center (GCRC). Three cores of the PCRC will be involved: the Biostatistics Core, the Genetics Core Laboratory and the Bioanalytical Core Laboratory. In addition, to increase the statistical power of this study, the applicant has assembled an international collaborative group that will conduct identical protocols and submit the data to the study center at CNMC. Future studies will test several other drugs with potential to improve muscle strength in DMD. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •
Project Title: MOLECULAR ANALYSIS OF THE YEAST ACTIN CYTOSKELETON Principal Investigator & Institution: Drubin, David G. Professor; Molecular and Cell Biology; University of California Berkeley Berkeley, CA 94720 Timing: Fiscal Year 2001; Project Start 01-JUL-1989; Project End 30-JUN-2002 Summary: Biochemical and genetic approaches will be used to study actin assembly in yeast. Principles established are likely to apply to more complex eukaryotes where actin dynamics underlie diverse cellular processes and where defective cytoskeleton function contributes to conditions such as muscular dystrophy, certain hereditary anemias, and cancer. The following aims will be pursued: (1) Actin nucleotide-binding pocket mutant. To test physiological importance of actin ATP hydrolysis and Pi release, and to genetically identify regulators of filament stability, we will take advantage of a unique
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actin mutant. The V159N mutation uncouples the actin nucleotide cycle from filament destabilization. Specifically, we will test the role of rapid actin filament turnover in pheromone-induced cellular morphogenesis and cortical actin patch motility, and will use the V159N mutant to genetically identify regulators of actin dynamics. (2) Biochemical and structure-function analysis of the cofilin-actin interaction. Our isolation of yeast cofilin, elucidation of its three dimensional molecular structure, and demonstration that it promotes actin filament disassembly in vivo, provide a strong foundation for further studies of this important and ubiquitous protein. The molecular models of yeast cofilin and actin filaments will now be docked, providing novel insights into the mechanism of cofilin-promoted filament disassembly. To more fully elucidate steps regulating the assembly/disassembly cycle, we will identify factors which stimulate formation of ATP-actin monomers from ADP-actin:cofilin complexes formed during disassembly. (3) Genetic analysis of cofilin regulation and regulation of actin filament stability. In response to regulatory signals, changes in actin assembly typically occur on time scales that mandate regulation by second messengers and posttranslational modification. Since genetic approaches provide powerful avenues to elucidation of regulatory pathways, proteins which regulate cofilin will be identified by genetic suppression. These studies are important for determining how cells trigger rapid cytoskeletal rearrangements required for diverse processes including morphogenesis and cytokinesis. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •
Project Title: MOLECULAR CELL BIOLOGY GORDON CONFERENCE Principal Investigator & Institution: Walter, Peter; Professor; Gordon Research Conferences Gordon Res Ctr C/O Univ of Rhode Island Kingston, RI 02881 Timing: Fiscal Year 2001; Project Start 01-JUL-2001; Project End 30-JUN-2002 Summary: A basic knowledge of cell biology is a requisite for understanding the defects in cell function that cause human diseases, including many cancers, muscular dystrophy, neurodegenerative disorders, blistering skin diseases, and cardiovascular disease. In recent years, cell biologists have played an increasing role in elucidating the mechanisms underlying genetic disorders, and understanding the biology of eukaryotic cells now becomes key in the quest to develop new and improved methods for the prevention, diagnosis and therapy of human disease. The 2001 Gordon Conference on Molecular Cell Biology focuses on recent developments in cell biology that were instrumental in determining genetic bases of diseases and now provide insights into methods for diagnosis and prevention of disease. The key features of this meeting are its diversity and scientific excellence. Emphasis is on cutting-edge science leading to new scientific principles and novel approaches to cell biology. A wide range of topics is represented, including cell cycle, cell polarity and movement, cell adhesion, genetic diseases, cell biology and disease. The organizers are Peter Walter and Ira Herskowitz (both at University of California, San Francisco). The meeting will bring together and foster discussion among world- renowned cell biologists. Participants will present their most recent and exciting results involving a number of model systems and using a variety of novel technical approaches. Nine sessions, each involving four major talks, are planned. Time will be reserved at the end of each session for short oral presentations on breaking developments. Thirty-five speakers, all leaders in their fields, have agreed to attend; approximately 30% of these are women. One more person will be invited. Daily poster sessions will enable all participants to present and discuss their most recent results. There will be abundant opportunities for informal discussion among speakers,
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postdoctoral fellows, and graduate students. This grant requests partial support for this exciting meeting. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •
Project Title: MOLECULAR GENETIC CHARACTERIZATION OF MYOTONIC DYSTROPHY Principal Investigator & Institution: Krahe, Ralf; Medical Microbiol & Immunology; Ohio State University 1800 Cannon Dr, Rm 1210 Columbus, OH 43210 Timing: Fiscal Year 2001; Project Start 24-SEP-2001; Project End 31-DEC-2001 Summary: (provided by applicant): The myotonic dystrophies (DM) are now collectively recognized as a clinically and genetically heterogeneous group of neuromuscular disorders, characterized by autosomal dominant inheritance, muscular dystrophy, myotonia, and multi-system involvement. Recent work by others and us indicates at least two more DM loci in addition to DM1, the (CTG)n expansion in chromosome 19q13.3. Multiple families with clinically variable presentation from predominantly distal to exclusively proximal muscle involvement show linkage to a locus in 3q21, designated DM2. However, several families with similar presentations have been excluded from this region. Thus, there is at least a third DM locus (DM3), which has yet to be mapped. The long-term goal of this proposal is the identification of DM2 in the families mapping to 3q21, and the mapping and cloning of the remaining gene(s) in the DM2-unlinked families. The characterization of the underlying mutations will be the basis for phenotype/genotype correlations. Three specific aims are proposed: (1) to clone and characterize DM2 in 3q21; (2) to clone and characterize the gene(s) in DM2unlinked/DM3 families, and (3) to globally expression profile DM muscle with DNA microarrays. Collaborating with clinical groups from the USA and Europe, we have ascertained 57 families with clinically similar phenotypes, which are negative for the DM1 (CTG)n expansion or any of the other known myotonia loci. Ten of 21 families suitable for linkage analysis show linkage to 3q21, while 11 are unlinked. We have substantially narrowed the DM2 critical region, generated a physical transcript map and started to examine functional-positional candidate genes, using various mutation detection assays. For DM3 we propose the same strategy of positional cloning that has proved successful for DM2. Genome-wide expression profiling of DM muscle will identify dysregulated genes and provide valuable functional clues about potential candidate genes and complex cellular candidate pathways, the overall pathophysiology of DM, and potential molecular therapeutic targets. The identification of these novel genes and the characterization of their mutations and pathophysiological role(s) are the first step in developing potential therapies for patients suffering from these inherited myotonic dystrophies. Moreover, as the cellular pathologies among the different myotonic dystrophies show considerable overlap, the identification of the genes underlying DM2 and DM3 and their corresponding expression profiles may also provide valuable insights into the pathology of DM1, which continues to elude researchers. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen
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Project Title: MODELS
MOLECULAR
GENETICS
OF
MUSCULAR/NEUROSENSORY
Principal Investigator & Institution: Nishina, Patsy M. Staff Scientist; Jackson Laboratory 600 Main St Bar Harbor, ME 04609 Timing: Fiscal Year 2002; Project Start 15-APR-2002; Project End 31-MAR-2006
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Summary: (provided by applicant): We have recently identified a spontaneous mouse mutant, veils (vis), that has retinal vasculopathy, hearing loss and progressive muscle wasting, phenotypes reported for many human diseases, such as Coat's disease, syndromic and non-syndromic congenital hearing loss, and muscular dystrophy, respectively. We have mapped veils to a 0.19+/-0.13 cM interval on mouse Chr. 8 in a 1,072 meiotic recombinant cross and established the physical contig of the critical region. Portions of human Chrs. 2, 4q, 8, 13, 17, 18, l9p and 22 map to this region, the breakpoints of which have yet to be refined. Interestingly, veils has many, if not all of the phenotypes reported for the disease fascioscapulohumeral muscular dystrophy la (FSHD), the third most prevalent muscular dystrophy that affects 1/20,000 and maps to human Chr. 4q35. Also, a neuromyopathy associated with a highly variable age-of-onset maps to Chr. l9pl3. Veils is a potential genetic and/or phenotypic model for these diseases. The veils mouse is also unique in that it shows retinal lamination abnormalities, a phenotype that has not previously been reported in the literature. In order to understand the biological mechanisms that underlie the disease processes and identify the biochemical pathways that are affected in different tissues, we will: (a) positionally clone the veils gene and identify the mutation in the second allele myd and test the hypothesis that the phenotypic differences between v/s and myd are explained by allelic heterogeneity; (b) begin to identify genes in the genetic background that can significantly alter the disease phenotypes of vis/vis mice; and (c) test the hypothesis that the observed phenotypes are the result of developmental defects rather than degenerative processes. Identification of disease causing genes and animal models is extremely important. Many diseases in humans, especially those involving the eye, if identified early enough, can be treated to attenuate the disease process. If no treatment is currently available, knowing the molecular basis of the disease may provide insights to new treatment regimens and the models can then be used to test those therapeutics. Finally, knowledge of the disease causing genes may lead to an understanding of pathways that are critical in maintaining normal function and physiology of the organism and perhaps, may identify therapeutic targets for prevention of muscle wasting, and vision or hearing loss. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •
Project Title: MOLECULAR GENETICS OF PRONUCLEAR FUNCTIONS IN DROSPHILA Principal Investigator & Institution: Wolfner, Mariana F. Professor; Molecular Biology and Genetics; Cornell University Ithaca Office of Sponsored Programs Ithaca, NY 14853 Timing: Fiscal Year 2002; Project Start 01-MAY-1991; Project End 31-AUG-2006 Summary: (provided by applicant): To initiate development, a newly fertilized egg must generate pronuclei that can combine to create a zygotic genome capable of initiating mitosis. The fertilized egg must also stimulate translation of previously quiescent, maternally deposited mRNAs. The goal of this proposal is to increase our understanding of this critical, but incompletely understood, developmental stage of "egg activation" in the model organism Drosophila. The first specific aim focuses on the function of an important player in the fertilized egg: the "Young Arrest" (Ya) gene. YA is a maternally encoded nuclear lamina protein that is essential for male and female pronuclei to initiate their first mitotic division. Our phenotypic analysis of Ya mutants suggests either that YA mediates changes in chromatin condensation needed for passage into S phase of the first mitosis, or alternatively that it replaces a meiotic protein that is inhibitory to subsequent mitotic cycles. The experiments described in this aim will test these hypotheses for YA function, and may further identify other molecules that interact
66 Muscular Dystrophy
with YA in fulfilling its roles. The results of these experiments will elucidate molecular changes necessary to transition frommeiosis to mitosis. We also expect these results to be of relevance to the mechanism of human diseases, such as Emery-Dreifuss Muscular Dystrophy, that are caused by mutations in nuclear lamina proteins. The second aim will investigate the implications of our finding that the subcellular location of YA changes during development. YA is excluded from nuclei during oogenesis, but is able to enter nuclei after egg activation. During the same transition, there are also changes in YA?s phosphorylation state. We will test whether the change in YA?s ability to enter nuclei is a direct consequence of changes in its phosphorylation state, and whether MAP kinase mediates these events. We will also identify additional components of a macromolecular complex we have identified that retains YA in the cytoplasm prior to egg activation. The third aim of the proposal is designed to achieve a broader view of the molecular events during egg activation. We will determine whether ovulation, which we have shown to trigger egg activation in Drosophila, causes a rise in calcium, parallel to findings in other systems. We will also test whether modulation of phosphorylation state, such as we see with YA, happens to many proteins during egg activation. Such modulation could mediate the rapid, concerted changes in egg physiology that occur at that time. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •
Project Title: MOLECULAR DYSTROPHINOPATHIES
IDENTIFICATION
OF
CANINE
Principal Investigator & Institution: Smith, Bruce F. Associate Professor; Scott-Ritchey Research Center; Auburn University at Auburn Auburn University, AL 36849 Timing: Fiscal Year 2002; Project Start 05-AUG-2002; Project End 31-JUL-2005 Summary: (provided by applicant): Duchenne muscular dystrophy is a common inherited disease, affecting approximately 1 in 3000 live male births. Currently, there is no effective therapy for this disease, however, new therapies are being proposed that offer hope to patients and their families. These therapies must be evaluated for their efficacy in the most stringent manner possible, and in the case of DMD, that requires an appropriate animal model. The long term GOAL of this project is to characterize the molecular defects present in 3 new canine models of dystrophin deficiency. It is hypothesized that these models accurately reflect the depth and breadth of mutations and their effects that is seen in the human population. Current murine models require that multiple genes be knocked out to show the same disease that the loss of dystrophin causes in boys. The canine model system is the only model which appropriately reflects the relentlessly progressive and ultimately fatal disease of boys. However, the complexity of the dystrophin gene and thus the variety of mutations possible, require the availability of multiple models in which to test therapies. The best source of these models continues to be spontaneously occurring canine disease. This severely handicaps the utility of these models in evaluating new therapies. This project will not only elucidate the mutation in these three new canine models, but it will also create a set of tools that will allow investigators worldwide to rapidly evaluate further spontaneous cases of canine muscular dystrophy for their usefulness, both in exploring new therapies and in gaining new insight into the mechanism behind Duchenne muscular dystrophy. Specifically, we propose to use panels of monoclonal antibodies with known specificity to dystrophin, simultaneously with PCR amplification of the coding sequence to rapidly scan for mutations. Suspicious areas will be sequenced to determine if the mutation is contained within. Once the mutations are identified, their effect on transcription, translation and the presence of dystrophin will be evaluated and
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compared to similar human mutations to determine if there is a pathophysiological correlation between species and their mutations. Successful completion of this project will result in the addition of three models of human dystrophin deficiency to the tools available to investigators seeking novel treatments. The correlation of these mutations with the clinical course of the disease will allow therapies to be evaluated under a variety of clinical circumstances. These mutations will provide new and different genetic backgrounds upon which various therapies, and in particular genetic therapies, may be examined in a large, outbred animal species. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •
Project Title: MOLECULAR MECHANISMS OF MYOTONIC DYSTROPHY Principal Investigator & Institution: Timchenko, Lubov T. Medicine; Baylor College of Medicine 1 Baylor Plaza Houston, TX 77030 Timing: Fiscal Year 2002; Project Start 01-SEP-1997; Project End 31-AUG-2007 Summary: (provided by applicant): Myotonic dystrophy (DM) is a neuro-muscular disease with a complex inheritance and an extremely complex molecular pathophysiology. We have suggested that unstable CTG repeats responsible for DM cause the disease at the RNA level via recruitment of specific RNA-binding proteins. We identified a CUG RNA-binding protein, CUGBP 1, and showed that this protein is recruited by CUG repeats into heavy RNA-protein complexes in cardiac tissue from DM patients. In order to investigate the role of CUGBP 1 in skeletal muscle differentiation, we generated primary skeletal muscle lines from DM patients and showed that a significant portion of DM cells fail to exit cell cycle during differentiation and that DM cells are able to proliferate. The failure of DM cells to differentiate is accompanying with a failure to accumulate CUGBP1 in cytoplasm. Our data show that CUGBP1 regulates translation of several mRNAs, including mRNA coding for an inhibitor of cell cycle, p21. p21 plays a key role in the differentiation of skeletal muscle. The major hypothesis of this application is that, under normal conditions, 1) CUGBP1 regulates cell cycle withdrawal in skeletal muscle via induction of p21 translation. 2) In DM skeletal muscle cells, expansion of CUG repeats within the mutant DMPK mRNA recruits CUGBP1 leading to the trapping CUGBP1 in nuclei and to inhibition of its cytoplasmic function: induction of p21. 3) The reduction of p21 in DM muscle cells results in a delay in exit from the cell cycle during muscle differentiation. Specific Aim I will define molecular mechanisms by which CUGBP1 is trapped in nuclei of DM differentiated cells. Specific Aim II examines the role of cytoplasmic CUGBP1 in p21-dependent regulation of skeletal muscle differentiation. Myoblast cell cycle progression and exit from the cell cycle will be examined in DM patients and in cell cultures with reduced levels of CUGBP 1. Specific Aim III will examine whether an increase of CUGBP 1 in nuclei of DM cells affects skeletal muscle differentiation. Myoblast cell cycle withdrawal and efficiency of myoblast fusion will be examined in cells derived from transgenic mice overexpressing CUGBP1. p21-dependent and p21-independent pathways will be examined. We will test whether other CUG repeats binding proteins are also affected in DM skeletal muscle. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen
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Project Title: MOLECULAR PATHOPHYSIOLOGY OF FACIOSCAPULOHUMERAL MUSCUL* Principal Investigator & Institution: Chen, Yi-Wen; Children's Research Institute Washington, D.C., DC 20010
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Timing: Fiscal Year 2001; Project Start 28-SEP-2001; Project End 31-MAY-2004 Summary: (provided by applicant): Facioscapulohumeral muscular dystrophy (FSHD) is one of the most common inherited muscle diseases following Duchenne muscular dystrophy and myotonic dystrophy. The disorder is autosomal dominant with nearly complete penetrance (95%) by age 20. Severity of muscle involvement in FSHD is extremely variable, ranging from elderly individuals with mild facial weakness to wheelchair bound children. Besides variability between individual patients, FSHD patients often show enigmatic asymmetry of muscle involvement. This disease feature permits a novel experimental design, where progression of the disease can be studied within a single patient at a single time point. Previous studies showed a statistically significant correlation between severity of clinical presentation and the deletion of D4Z4 repeats on chromosome 4q35 in patients with FSHD. Current hypotheses center on a position effect of telomeric sequences on genes in or near the deletion site, however the molecular mechanisms underlying this disease are far from clear. In our study, we hypothesize that FSHD patient muscle shows a disease-specific expression profile, relative to other muscle disease (Duchenne muscular dystrophy, alpha-sarcoglycan deficiency, juvenile dermatomyositis, and dysferlin deficiency). In addition, we hypothesize that one can identify a subset of the FSHD-specific genes will be shown to correlate with progression of-muscle involvement in FSHD muscle by comparing expression changes correlated with clinically-affected vs. unaffected muscles within single dystrophy patients. In our preliminary data, we have defined an FSHD-specific set of 29 genes that are candidates for primary involvement of disease pathogenesis by using the HuGeneFL array (-6,000 full length genes). In this proposal, we plan to broaden the number of genes studied, so that a genome-wide set of genes implicated in the primary etiology can be defined. Specifically, we will extend our truly promising preliminary data to over 60,000 genes and EST sequences included on the Human genome U95A, B, C, D, E stock chips, as well as the > 2,000 human muscle ESTs on our custom-produced MuscleChip. In addition, a custom glass slide array consisting of - 200 genes and ESTs from 4q35 and lOq26 will be used to identify FSHD region specific alterations in gene expression. All FHSD-specific ESTs identified will be characterized in detail. Further studies will likely include the delineation of a complete picture of the pathophysiology of FSHD, as well as identification of functional SNPs in the refined gene list that correlate with disease severity. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •
Project Title: MOLECULAR STUDIES IN AUTOSOMAL DOMINANT LIMB GIRDLE MUSCULAR DYSTROPHY(LGMD) Principal Investigator & Institution: Vance, Jeffery M. Professor; Duke University Durham, NC 27706 Timing: Fiscal Year 2001 Summary: Limb Girdle Muscular Dystrophy is major form of muscular dystrophy affecting both adults and children. The autosomal recessive LGMD have made major progress in understanding these disorders through positional cloning and candidate protein analysis. We propose to take a similar approach to the autosomal dominant form of this disease. Through the previous funding period we have collected 23 autosomal dominant families (LGMD1) comprising 795 individuals. From this group we have previously linked a large family to chromosome 5 (LGMD1a). Recently, we have identified another LGMD1 locus on chromosome 7q36 (LGMD1D). In collaboration with Dr. Carol Westbrook, we have previously established a 2 megabase YAC/BAC contig across the chromosome 5 LGMD1A region and have screened 33 ESTs lying within this
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region for muscle expression. Currently, we are characterizing and evaluating positive clones for potential mutations. We propose to continue to narrow the LGMD1A minimal candidate region and perform candidate gene analysis using direct selection if needed, to identify the gene defect. Once the LGMD1A gene defect is identified, we will begin mapping the LGMD1D region on chromosome 7q36 to identify this gene defect. Physical mapping for the chromosome 7q36 region will be done in conjunction with Dr. Eric Green, who is responsible for forming contigs on chromosome 7 for the sequencing initiative of the chromosome for Washington University. Three large YAC contigs already span the current LGMD1D region, with two gaps. We will also utilize direct selection for this analysis but we anticipate sequence data to be available to assist in identifying the LGMD1D gene. Once the LGMD1A or LGMD1D gene is identified, we will work with our consultant Dr. Lou Kunkel to evaluate the function of the protein, assess the extent of mutations in small and isolated LGMD cases, and evaluate any genotype/phenotype correlations. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •
Project Title: DYSTROPHY
MOLECULAR
STUDIES
OF
FACIOSCAPULOHUMERAL
Principal Investigator & Institution: Figlewicz, Denise A. Professor; University of Rochester Orpa - Rc Box 270140 Rochester, NY 14627 Timing: Fiscal Year 2001 Summary: This abstract is not available. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •
Project Title: MTOR SIGNALING IN SKELETAL MYOGENESIS Principal Investigator & Institution: Chen, Jie; Assistant Professor; Cell and Structural Biology; University of Illinois Urbana-Champaign Henry Administration Bldg Champaign, IL 61820 Timing: Fiscal Year 2003; Project Start 01-JUN-2003; Project End 31-MAY-2008 Summary: (provided by applicant): Skeletal muscle differentiation is a well-orchestrated process regulated by autocrine, paracrine, and endocrine factors via multiple signal transduction pathways. The bacterial macrolide rapamycin inhibits a wide spectrum of cellular functions, from proliferation, growth, to differentiation, and it has served as a powerful tool to probe relevant signaling pathways. While the rapamycin-sensitive pathway is under intensive investigation in the context of cell growth and proliferation, its importance in skeletal muscle development is only beginning to be recognized. The mammalian target of rapamycin - mTOR- is a multi-functional protein that serves as a central component of multiple signaling pathways that are inhibited by rapamycin. Preliminary studies from this investigator's laboratory have revealed an essential function of mTOR in skeletal muscle differentiation and the existence of novel mechanisms of mTOR signaling. The proposed studies are designed to test the hypothesis that an mTOR pathway distinct from that in cell growth and proliferation regulates skeletal muscle satellite cell differentiation by controlling the autocrine production of IGF-I and IGF-II. With a combination of biochemical, molecular, cellular and genetic approaches, and in the systems of a tissue culture model (C2C12) and mouse primary satellite cells, the specific aims of this proposal are to investigate (1) regulation of IGF autocrine production by mTOR; (2) involvement of a phospholipase D-phosphatidic acid-mTOR pathway in myogenesis; and (3) mTOR's structure-function relationship and novel signaling partners in differentiation. Knowledge gained in these
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studies will not only provide invaluable insights into the signaling mechanisms of the pleiotropic mTOR pathway, but also make significant contributions to the molecular understanding of skeletal muscle development, which is tightly coupled to healthrelated issues such as muscular dystrophy, exercise-induced hypertrophy, and agingrelated atrophy. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •
Project Title: MULTIPLE PEPTIDE SYNTHESIZER - AN INTEGRATED SYSTEM Principal Investigator & Institution: Kurosky, Alexander; Professor; Human Biol Chem and Genetics; University of Texas Medical Br Galveston 301 University Blvd Galveston, TX 77555 Timing: Fiscal Year 2002; Project Start 01-MAY-2002; Project End 30-APR-2003 Summary: (provided by applicant): Support is requested for an automated solid-phase peptide synthesizer, preparative high-performance liquid chromatography equipment dedicated to peptide purification, and a vacuum concentrator for drying solvents used during synthesize and purification. This integrated system of instruments for producing synthetic peptides will replace aging ten-year-old equipment that is now unsupported by the manufacturer. The selected synthesizer, a Rainin Symphony/Multiplex with the Cascade Combinatorial Reactor, is a multiple peptide synthesizer that can synthesize up to twelve peptides simultaneously and independently, allowing us to better meet increased demands for synthetic peptides for NIH-funded researchers at the University of Texas Medical Branch (UTMB). The beneficiary users of the requested equipment include a multidisciplinary group of fourteen predominantly NIH-supported investigators (9 major and 5 minor users; 22 funded NIB grants totaling $4 million dollars annual direct costs) representing several clinical and basic science departments at UTMB, e.g. Human Biological Chemistry and Genetics, Microbiology and Immunology, Pediatrics, Pathology, Anatomy and Neuroscience, as well as Internal Medicine. Examples of diseases under investigation by these synthetic peptide users include those involving or related to muscular dystrophy, allergy, asthma, cancer, xenobiotics, environmental toxicology, mutagenesis, and gastroenterology. The Peptide Synthesis Core is one of five cores within the UTMB Protein Chemistry Laboratory; the others are the Protein/DNA Sequencing, the Proteomics, the Mass Spectrometry, and the Protein Expression Cores. Together, these core facilities provide a wide range of services for the entire University campus including multiple campus research centers. Acquisition of the requested instrumentation will significantly enhance the ability of NIH-funded investigators to conduct their ongoing hypothesis-driven research and, moreover, will extend their research opportunities in the future to higher levels of productivity and scientific impact. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen
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Project Title: MUSCLE GENE REGULATION AND CASSETTES FOR GENE THERAPY Principal Investigator & Institution: Hauschka, Stephen D. Biochemistry; University of Washington Seattle, WA 98195 Timing: Fiscal Year 2003; Project Start 01-MAY-1976; Project End 30-APR-2008 Summary: (provided by applicant): This project combines a basic research component aimed at understanding how muscle genes are regulated, with an applied component aimed at designing regulatory cassettes for expressing therapeutic proteins in striated muscle. Prior basic studies concentrated primarily on understanding how the mouse M-
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creatine kinase (MCK) gene enhancer and promoter control MCK expression in skeletal and cardiac muscle. These studies will continue but much of our future effort will be directed toward mapping three additional regulatory regions which confer higher transcriptional activity to the enhancer-promoter complex, and a fourth region which confers gene copy number-dependent expression. Control elements within these regions will be identified and these sequences will then be used to identify and understand the function of their associated transcription factors. Applied aspects of the project utilize the basic information above, together with published data concerning other striated muscle genes, to construct regulatory cassettes that will be useful in treating skeletal and cardiac muscle diseases, and in therapeutic situations which could benefit from using skeletal muscle as a source of secreted proteins; e.g., hormone and clotting factor deficiency diseases, and tissue healing. Goals for these studies are to optimize the transcriptional activity of cassettes designed to function in different striated muscle types, while simultaneously maintaining tight muscle-specific transcription so as to prevent therapeutic gene expression in immune system and other non-muscle cells that may be inadvertently transduced and damaged by mis-targeted gene therapy vectors. Two additional goals are to build miniature regulatory cassettes that will be compatible with packaging therapeutic cDNAs such as mini- and micro-dystrophins into AAV and other small viral vectors, and to build high activity muscle-specific cassettes expressing externally regulatable transcription factors that will selectively transcribe therapeutic cDNAs in response to non-harmful drugs, thus permitting the external manipulation of therapeutic gene product levels. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •
Project Title: MUSCLE RESPONSE TO STRESS IN CANINE MUSCULAR DYSTROPHY Principal Investigator & Institution: Childers, Martin K. Phys Med and Rehabilitation; University of Missouri Columbia 310 Jesse Hall Columbia, MO 65211 Timing: Fiscal Year 2001; Project Start 01-MAR-1999; Project End 28-FEB-2003 Summary: This project will provide the applicant with the research skills required to develop and assess rehabilitation treatments that enhance function for patients with muscular dystrophy. Throughout a doctoral program in physiology, a major portion of effort will be devoted to a mentored research project which will examine the relationship between mechanical stress and muscle fiber injury in a canine homolog of Duchenne muscular dystrophy. The central hypothesis of this research is that fiber damage in dystrophin-deficient muscle results, in part, from an exaggerated response to mechanical stress incurred during contraction. Furthermore, muscles involved in lengthening contractions are subject to greater stress than other muscles, and are preferentially injured. The central hypothesis will be tested in selected hindlimb muscles of dystrophic dogs by evaluating cellular and physiological features of muscle fiber response to varying levels of imposed stress. Although the mdx mouse is more readily available and a more commonly used experimental model, the dystrophic dog expresses clinical features analogous to humans with Duchenne muscular dystrophy. Aim 1 will correlate muscle membrane damage with myofiber necrosis: Aim 2 will compare regenerative features in muscles involved in lengthening contractions with muscles involved in shortening contractions: Aim 3 will determine if a lower threshold to stressinduced injury exists in dystrophic fibers compared to controls: and Aim 4 will determine if reducing mechanical stress during growth will eliminate or decrease the exaggerated fiber necrosis and remodeling seen in the adult gastrocnemius muscle. It is anticipated that findings will improve the understanding of how dystrophic muscle
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responds to physical stress resulting in improved treatment for patients with Duchenne muscular dystrophy. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •
Project Title: MUSCULAR DYSTROPHY COOPERATIVE RESEARCH CENTER Principal Investigator & Institution: Moxley, Richard T. Professor; Neurology; University of Rochester Orpa - Rc Box 270140 Rochester, NY 14627 Timing: Fiscal Year 2003; Project Start 30-SEP-2003; Project End 31-MAY-2008 Summary: (provided by applicant): The myotonic dystrophies (DM1 and DM2), which are the most common form of adult-onset muscular dystrophy, are autosomal dominant diseases with similar clinical presentations. Remarkably, DM1 and DM2 are caused by unstable microsatellite expansions in the untranslated regions of two different genes, DMPK and ZNF9. To explain how these non-coding expansion mutations lead to dominantly inherited neuromuscular disorders, we have proposed a toxic RNA model for the myotonic dystrophies. Transcription of the mutant DM1 (CTG)n and DM2 (CCTG)n alleles leads to the production of unusual RNA transcripts with (CUG)n and (CCUG)n repeat expansions. These expansions fold into stable double-stranded (ds) RNA structures that recruit and then sequester a family of dsRNA-binding factors, the muscleblind proteins. Because this toxic RNA model suggests that DM1 and DM2 diseases are due to loss of muscleblind protein function, we have derived muscleblind 1 (Mbnll) knockout mice. This proposal is designed to test our working hypothesis that Mbnll-/- knockout mice will be a useful model to examine underlying molecular mechanisms involved in myotonic dystrophy disease pathogenesis. First, we will characterize the Mbnll-/-muscle phenotype and test the hypothesis that Mbnll is required for proper alternative splicing and function of the chloride channel CIC-1. Deficiency of this ion channel has been recently implicated as the cause of DM1- and DM2- associated myotonia. The stoichiometric relationship between toxic RNA and binding protein will be examined by breeding Mbnll knockout mice with lines of transgenic mice that express (CUG)n RNA at different levels. Second, the possibility that muscleblind proteins influence CIC-1 chloride channel levels by interacting with alternative splicing, and/or other, factors will be examined. Third, the hypothesis that the myotonia phenotype can be rescued using recombinant adeno-associated virus mediated expression of wild type adult CIC-1 will be tested. Finally, we will investigate if additional disease-associated phenotypes result from deletion of the entire Mbnll gene, from tissue-specific Mbnll expression or from combinatorial loss of all three muscleblind (Mbnll, Mbnl2/Mbnll, Mbnl3/Mblx) genes. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen
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Project Title: MYELOID CELL FUNCTION IN MUSCULAR DYSTROPHY Principal Investigator & Institution: Tidball, James G. Professor; Physiological Sciences; University of California Los Angeles 10920 Wilshire Blvd., Suite 1200 Los Angeles, CA 90024 Timing: Fiscal Year 2001; Project Start 24-SEP-2001; Project End 31-AUG-2006 Summary: (provided by applicant): Duchenne muscular dystrophy (DMD) is the most common, inherited, lethal disease of childhood. Although mutations in the dystrophin gene are primarily responsible for DMD and animal models of DMD, many features of dystrophinopathies indicate that secondary processes can contribute substantially to pathology. Recent findings have indicated that the immune system can contribute significantly to the pathological progression of dystrophin-deficiency in the mdx mouse
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model of the disease. The long-term goal of our studies of the pathology of dystrophindeficiency is to identify the specific immune cells and mechanisms that promote the pathology of dystrophin-deficiencies, after which we will use that information for the development of immune-based therapeutics. Although our preliminary data implicate both myeloid and lymphoid cells in promoting the dystrophic pathology, the studies proposed here will focus on cytotoxic mechanisms that are mediated by macrophages and eosinophils in dystrophic muscle. Our rationale for focusing on these specific myeloid cells is that our preliminary findings strongly implicate these cells in promoting the pathology of dystrophin-deficiency through both innate and acquired immune responses. Our general strategy will be to assess the effect on muscle pathology of depletion of specific myeloid cell populations from the dystrophic mdx mouse. In addition, the effect of those depletions on the lifespan of the dystrophic mdx/utrophindeficient mice will be assessed because these mice die from muscular dystrophy at an early age. We will also test whether introducing null mutations of the inducible nitric oxide synthase gene or major basic protein gene into mdx mice will reduce muscle pathology, because our findings implicate cytotoxic pathways in the mdx pathology that involve the products of these genes. Results of the study proposed here will permit us to determine whether therapeutic approaches that are based on reducing myeloid cell mediated pathology can be productive approaches to the treatment of these forms of muscular dystrophy. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •
Project Title: MYOGENIC GROWTH AND DIFFERENTIATION Principal Investigator & Institution: Olwin, Bradley B. Professor; Molecular, Cellular & Dev Biol; University of Colorado at Boulder Boulder, CO 80309 Timing: Fiscal Year 2001; Project Start 15-JUL-1999; Project End 30-JUN-2004 Summary: Aging, severe injury and skeletal muscle diseases all result in the loss of skeletal muscle tissue. Although skeletal muscle has a large regenerative capacity, a permanent loss of skeletal muscle tissue can occur in each of these clinical occurrences. The molecular mechanisms that regulate skeletal muscle regeneration are largely unknown. Implicated in skeletal muscle growth and regeneration are extracellular factors that include the insulin-like growth factors (IGFs), the fibroblast growth factor (FGFs), the transforming growth factor family (TGFs and GDFs), and hepatocyte growth factor (HGF). The loss of skeletal muscle function occurring in humans with muscular dystrophy and aging has been attributed to a loss of muscle regenerative capacity, but little is known concerning the mechanisms involved in this process. Myoblast transfer therapy to alleviate these symptoms is largely unsuccessful in animals and humans due to the death of greater than or equal to 95 percent of myoblasts following injection and the poor proliferative potential of the remaining cells. As an alternative, gene therapy with adenoviruses may be difficult due to the large mass of muscle tissue. It is likely that a combination of these procedures will be required to eventually cure muscle diseases and recover muscle tissue in patients exhibiting severe cachexia. In order to make myoblast transfer therapy successful, it will be necessary to manipulate the decision of a committed myoblast to proliferate, remain quiescent and undifferentiated, or to terminally differentiate and undergo cell fusion. A primary goal of the proposed research is to understand the relationships that regulate proliferation and differentiation in myogenic cells. The specific aims are to: 1. characterize the molecular mechanisms that are utilized by intracellular FGF-2 to promote myoblast proliferation; 2. analyze potential MAPK phosphatase 1 (MKP1) substrates and determine their involvement in FGF-mediated repression of skeletal muscle differentiation; 3. identify unknown MKP1
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substrates that may act to mediate repression of differentiation by FGFs; 4. characterize MKP1 substrates identified in aim 3 and determine their involvement in repression of skeletal muscle differentiation. These goals will be accomplished by a combination of approaches that include the use of novel FGF-2 fusion proteins that partition into the cytoplasm via a receptor-independent mechanism, expression of mutant signal transducers, identification of unknown substrates by nanospray mass spectrometry, and determination that the identified MKP1 substrates are clinical regulators of skeletal muscle differentiation. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •
Project Title: MYOSIN GENE DIVERSITY AND FUNCTION Principal Investigator & Institution: Leinwand, Leslie A. Professor and Chair; Molecular, Cellular & Dev Biol; University of Colorado at Boulder Boulder, CO 80309 Timing: Fiscal Year 2003; Project Start 01-SEP-1981; Project End 31-JAN-2007 Summary: (provided by applicant): The formation of skeletal muscle and its adaptation to the environment requires precise temporal and spatial regulation of a host of proteins, including the molecular motor protein, myosin. The precise adaptation of myosin heavy chain (MyHC) genes requires coordinate regulation, yet, little is known about its molecular biology. We propose to define the molecular aspects of fiber type specificity and the pathways that regulate these genes. In mammals, there are 6 characterized skeletal muscle MyHC genes. Although muscle fibers expressing each of them have unique contractile velocities, the enzymatic properties of the individual motors remain elusive. We will express the 6 human skeletal MyHC head domains in an inducible mammalian system and characterize their biochemical and biophysical properties. Despite the perception that the sarcomeric MyHC gene family had been defined, examination of the human genome revealed a novel striated MyHC that we propose to characterize. We have found that it is expressed in cardiac and skeletal muscle and that phylogenetically, it appears most closely related to the alpha and beta MyHC genes. We will compare the sequence features of the coding, regulatory regions and the intron/exon organization of this gene in mouse and human. We will also determine its expression in development and in the adult and test whether wellcharacterized muscle adaptations alter its pattern of expression. Until recently, there had been no diseases associated with mutations in skeletal MyHC. However, a mutation in the MyHC IIa gene has been reported which we propose to model in transgenic mice. We are also characterizing the IId gene of a childhood myopathy patient who appears to be null for its expression. An interesting feature of the MyHC gene family that may have relevance to Duchenne muscular dystrophy (DMD) is that the most abundant MyHC protein in rodents, IIb, is barely detectable in normal adults. However, we find its expression is induced in DMD. Because of the potential functional consequences of expression of this fast myosin motor, we will define the molecular basis for this species difference and its induction. Finally, we will extend our studies of an unusual cell type, the myofibroblast, which has properties of both muscle and nonmuscle cells, including expression of adult fast skeletal MyHCs, to understand the pathways that define these cells and distinguish them from skeletal muscle. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen
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Project Title: MYOSTATIN IN MUSCLE GROWTH AND REGENERATION Principal Investigator & Institution: Wagner, Kathryn R. Assistant Professor; Neurology; Johns Hopkins University 3400 N Charles St Baltimore, MD 21218
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Timing: Fiscal Year 2001; Project Start 15-MAY-2001; Project End 31-MAR-2006 Summary: (provided by applicant): Skeletal muscle grows and atrophies in response to environmental stimuli and has an impressive ability to regenerate following a variety of insults. The processes underlying muscle growth and regeneration are incompletely understood but are apparently governed by a number of growth and differentiation factors. Myostatin, a recently described member of the TGFbeta superfamily, appears to be a negative regulator of muscle growth. Targeted deletion of the myostatin gene in nice causes widespread and massive skeletal muscle hypertrophy and hyperplasia. This study will examine the mechanism of action of myostatin and its potential role in regeneration with three specific aims. First, the precise biological function of myostatin will be defined in vivo and in vitro. Myostatin null mice will be further characterized, particularly with respect to muscle progenitor cells. The normal, cellular pattern of myostatin expression will be determined by RNA analysis of myocytes in vitro and in situ. The biological effects of purified recombinant myostatin on myocytes will be examined in primary and established cell cultures. Second, 1he main focus of the project will be to identify the receptor to myostatin. The binding affinity and distribution of receptors will be determined by binding of radioiodinated myostatin to cultured cells, tissue membranes and embryo whole mounts. The receptor will then be cloned through an approach including expression cloning. Third, the potential role of myostatin in disease and regeneration will be explored in the null mutant mouse through models of myopathy including dystrophinopathy, crush injury and toxic insult. Understanding, and potentially modulating, the factors that influence muscle growth and regeneration. have important applications to myopathies, muscular dystrophies and muscle aging (sarcopenia). The proposed research will employ a variety of molecular biology, protein biochemistry, cell culture and histopathology techniques m order to study an apparently powerful negative regulator of muscle growth. In addition to the ultimate goal of providing clinical applications for muscle disease, this multidisciplinary approach should provide excellent training for a career integrating clinical myology and molecular neuroscience. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •
Project Title: MYOTENDINOUS JUNCTION FORMATION IN SKELETAL MUSCLE Principal Investigator & Institution: Kramer, Randall H. Professor; Stomatology; University of California San Francisco 500 Parnassus Ave San Francisco, CA 94122 Timing: Fiscal Year 2001; Project Start 01-FEB-1999; Project End 31-JAN-2004 Summary: (Adapted from investigator's Abstract): Craniofacial skeletal muscle defects occur in certain myopathies, such as muscular dystrophy; in congenital deformities, such as hemifacial microsomia and facial/palatal clefts; and as a result of surgical procedures for oral cancer or trauma. Success in the repair or replacement of muscle defects is limited by difficulty in transplantation and survival of muscle tissue. An important structure of muscle is the myotendinous junction (MTJ), which transduces force generated by muscle to its connective tissue attachment site. How this complex structure is formed in developing muscle or repaired after injury or disease is poorly understood. Attachment of the muscle fiber to the connective tissue appears to involve adhesion receptors, including the alpha7-beta1 integrin. In addition, during muscle development and repair, alpha7 integrin seems important for myoblast adhesion and motility. The long- term objective of the proposed studies is to further define the molecular mechanisms by which the laminin-binding alpha7 integrin organizes the MTJ in developing and regenerating skeletal muscle. The hypothesis is that the alternatively spliced isoforms of alpha7 not only regulate transient adhesion during myoblast motility
76 Muscular Dystrophy
but also form the long-lived MTJ. The specific aims are 1) to determine the expression levels and distribution of laminin-binding integrins during skeletal muscle development, 2) to analyze the functionality of alpha7,beta1 alternatively spliced isoforms, and 3) to determine the role of the alternatively spliced extracellular domain in regulating alpha7 activation. The experimental approach is first to define the developmentally complex expression patterns of the alpha7 splice variants and their ligands. Next, alpha7 isoforms will be analyzed for their role in cell motility and assembly of MTJ-like structures. Finally, the role of the extracellular domain splice variants in regulating alpha7 activity will be addressed using molecular approaches. These studies will enhance understanding of the structure and assembly of the MTJ and suggest new approaches in tissue engineering to promote reconstruction of craniofacial skeletal muscle defects caused by disease, trauma, or surgical procedures. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •
Project Title: NERVE-MUSCLE SYNAPSE ORGANIZING MOLECULES Principal Investigator & Institution: Fallon, Justin R. Professor; Neuroscience; Brown University Providence, RI 02912 Timing: Fiscal Year 2001; Project Start 01-AUG-1988; Project End 28-FEB-2006 Summary: (Adapted from applicant's abstract): This proposal has two overall, interrelated goals. The first is to deepen our understanding of how synapses are formed, shaped, maintained and eliminated. The second is to elucidate how the integrity of the muscle fiber membrane is maintained, with particular regard to muscular dystrophy. Agrin secreted from the nerve terminal induces the formation of nerve-muscle synapses. The agrin signaling receptor MuSK is essential for this induction. However, agrin does not bind MuSK directly and the mechanisms of MuSK activation and localization are unresolved. In the previous funding period we discovered a novel component of Torpedo electric organ postsynaptic membranes, biglycan. Biochemical studies show that this small leucine-rich repeat proteoglycan (SLRP) binds via distinct domains to a adystroglycan, the ectodomain of MuSK and to a-and g- sarcoglycan. Both biglycan and its homolog decorin induce MuSK tyrosine phosphorylation when added to cultured myotubes. Moreover, agrin-induced AChR clustering is greatly reduced on myotubes from biglycan null (biglycan-10) mice. Finally, serum creatine kinase levels are markedly elevated in biglycan-10 mice. Together, these observations point to an important role for biglycan and/or decorin in postsynaptic differentiation, and for biglycan in maintaining the integrity of the muscle cell plasma membrane. In the present proposal we will take a combined molecular, biochemical, cell biological, and genetic approach to elucidate the role of biglycan and decorin in synaptic differentiation and in maintaining muscle cell integrity. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen
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Project Title: NEUROBIOLOGY OF DISEASE -- TEACHING WORKSHOP Principal Investigator & Institution: Lipton, Stuart A. Director, Degenerative Disease; Society for Neuroscience 11 Dupont Cir Nw, Ste 500 Washington, DC 20036 Timing: Fiscal Year 2001; Project Start 01-AUG-1983; Project End 31-MAY-2006 Summary: The Society for Neuroscience (SFN) is the major professional organization for scientists who study the nervous system. An important goal of this organization is to encourage scientists in training to undertake research related to diseases of the nervous system. The objective of this grant application is to support teaching workshops that introduce young neuroscientists to current concepts about the etiology and pathogenesis
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of disorders of the nervous system. For each workshop, about 12 faculty are chosen by the Organizing Committee after eliciting proposals from the Society at large. Clinical presentations provide enrollees with an experience of the human dimension of particular diseases. Lectures cover both clinical research and relevant laboratory work. In addition to lectures, enrollees are given a choice of attending two of four small group workshops that emphasize either specific or methodological issues and encourage lively discussion. Since its inception, 20 workshops have been held, usually on the day prior to the start of the Society for Neuroscience meeting. Topics have included: Infections in the nervous system, epilepsy, Huntington's and Alzheimer's diseases, muscular dystrophy, multiple sclerosis, prion diseases, drug addiction, pain and affective disorders, stroke and excitotoxicity, neuromuscular diseases, amyotrophic lateral sclerosis, schizophrenia, migraine, mental retardation and developmental disorders, Tourette's syndrome and obsessive-compulsive disorder, and the neurobiology of brain tumors. Enrollment generally runs between 100 and 200 attendees. Most enrollees are graduate students or postdoctoral fellows. Current plans are to cover the following topics in the near future: Genes, free radicals, mitochondria and apoptosis in Parkinson's disease, AIDS dementia, peripheral neuropathy, pain, language disorders, and affective disorders. Other topics will be chosen depending on their potential interest to young neuroscientists, their impact on society and the quality of recent research related to that disease area. We are especially interested in covering diseases of the nervous system which are important clinically but which are in need of enhanced basic cellular and molecular understanding. Society members are encouraged to suggest topics in the SFN Newsletter. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •
Project Title: NGF AND MUSCLE DEVELOPMENT Principal Investigator & Institution: Wheeler, Esther F.; University of Texas San Antonio San Antonio, TX 78249 Timing: Fiscal Year 2003; Project Start 01-AUG-2003; Project End 31-JUL-2006 Summary: The purpose of the study proposed herein is to determine the biological function of NGF and the NGF Receptors in muscle development. The preliminary data indicate a novel role for NGF and its two receptors (p75NTR and trk A) during myoblast proliferation and differentiation. The p75NTR, a non-catalytic receptor, is expressed by proliferating myoblasts but ceases to be expressed when myoblasts fuse to form myotubes. At some point during fusion, the other NGF receptor, trk A (a tyrosinespecific kinase receptor), begins to be expressed by the fused myotubes. The expression patterns of the NGF receptors raise the possibility that NGF plays a role in myogenesis. The working hypothesis is that NGF mediates processes that mediate the viability and organization of differentiating myoblasts and the normal homeostasis of differentiated myofibers. The results of the study will hopefully reveal effects of NGF on muscle that can be exploited for therapies for preventing or treating the muscular degeneration that accompanies neurodegenerative diseases as well as Duchene's muscular dystrophy. To determine the biological function of NGF and its receptors during myogenesis, the change of expression of the receptors will be determined at different stages of myoblast differentiation in vitro. Once cell cultures have been established that mimic receptor expression in vivo, the signaling pathways the pathways activated by the p75NTR in myoblasts will be studied. Dominant negative mutations in two of the signal transduction molecules will be used to determine pathway interactions. The spatial/temporal expression of the the trk A receptor protein will be studied in vivo in order to determine the development time the receptor becomes active. To better characterize the NGF response in myocytes, C2C12 cells will be transfected with
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constructs that will make it possible to induce express the receptors at inappropriate times and the resulting cell lines will be tested for defects in development and differentiation. Finally, the muscle of null mutant mice for the two receptors will be examined in vivo and in vitro for changes in myoblast differentiation and muscle function. Taken together, the aims of the proposal will reveal new information about the role of NGF in the normal development and function of muscle. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •
Project Title: NON-RADIAL CELL MIGRATION IN CNS DEVELOPMENT Principal Investigator & Institution: Golden, Jeffrey A. Assistant Professor of Pathology; Children's Hospital of Philadelphia 34Th St and Civic Ctr Blvd Philadelphia, PA 19104 Timing: Fiscal Year 2003; Project Start 15-FEB-2003; Project End 31-DEC-2007 Summary: (provided by applicant): Epilepsy, mental retardation and structural anomalies of the brain often have a genetic etiology. Although they affect 3-5% of all children, the underlying pathogeneses for these disorders is poorly understood in most cases. Cell migration is a central component of normal central nervous system (CNS) development and disruptions in this process have been implicated in the development of multiple disorders such as Fukuyama Muscular dystrophy, Miller-Dieker Syndrome, Walker-Warburg Syndrome, and the Muscle-Eye-Brain syndrome to name just a few. Two primary patterns of cell migration are recognized during CNS development, radial and non-radial. While the cellular and molecular bases of radial cell migration, long considered the predominant mode of cell migration, have begun to be defined, the mechanisms of guidance for non-radial cell migration remain largely unexplored. Using lineage analysis, we have defined the developmental time and location where non-radial cell migration begins in the chick forebrain. Based on these data we have developed a model to explain the cellular and molecular mechanisms of non-radial cell migration. Our model is based on the hypotheses that cell surface molecules, secreted molecules, and extracellular matrix molecules guide non-radially migrating cells. This proposal will begin to address our hypothesis by 1) directly testing several components of our model, and 2) generate a mammalian model to further study one of the molecules we have identified as a component of non-radial cell migration in the chick. These data will certainly enhance our understanding of normal CNS development. Furthermore, we anticipate the data from these studies will provide insight into the pathogenesis of a variety of inherited and non-inherited conditions that afflict children such as epilepsy, mental retardation and structural malformations of the brain. This may ultimately lead to improvements in the diagnosis, management, and prevention of neurological diseases where abnormal cell migration has a pathogenetic role. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen
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Project Title: NOVEL APPLICATION OF STEM CELLS/ RETROVIRAL VECTORS Principal Investigator & Institution: Mulligan, Richard; Dana-Farber Cancer Institute 44 Binney St Boston, MA 02115 Timing: Fiscal Year 2001 Summary: Recent studies from our laboratory and others suggest that murine hematopoietic stem cells and perhaps other cell populations derived from nonhematopoietic organs, may possess the capacity to differentiate into a range of mature cell types distinct from those originally thought to be derived from the cells. This apparent 'plasticity' of stem cell populations offers new opportunities to expand the use of bone marrow transplantation, in conjunction with gene transfer, to treat congenital
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diseases which affect cells other than those of the blood. Such a strategy may be particularly important for the treatment of diseases in which the systemic delivery of cells or genes throughout the body is essential, such as muscular dystrophy. In this research program, we propose to (i) determine, in a comprehensive way, the spectrum of cell types than can be derived from different populations of stem cells isolated from the adult, (ii) to develop procedures for the isolation, manipulation, and transplantation of cells which lead to the optimized production and systemic engraftment of specific cell types, and (iii) to apply those procedures, along with the methods we have previously developed for the transduction of hematopoietic stem cells, to the evaluation of gene therapies for the treatment of specific congenital disease, using well characterized animal models. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •
Project Title: OXANDRIN (OXANDROLONE) IN THE TREATMENT OF CHRONIC MUSCLE DISEASES Principal Investigator & Institution: Rutkove, Seward B.; Beth Israel Deaconess Medical Center St 1005 Boston, MA 02215 Timing: Fiscal Year 2001 Summary: This abstract is not available. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen
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Project Title: PATHOGENESIS OF A NOVEL LIMB-GIRDLE MUSCULAR DYSTROPHY Principal Investigator & Institution: Hirano, Michio; Assistant Professor; Neurology; Columbia University Health Sciences New York, NY 10032 Timing: Fiscal Year 2001; Project Start 01-SEP-2001; Project End 31-JUL-2004 Summary: Since the initial identification of mutations in the dystrophin gene as the cause of Duchenne and Becker muscular dystrophies, molecular genetics has provided a plethora of new information and insights into the pathogeneses of muscle diseases. In particular, our understanding of the limb-girdle muscular dystrophies (LMGD) have been greatly enhanced. Fourteen forms of LGMD have been identified; of these, specific gene have been characterized in ten. This goal of this proposal is to identify the molecular genetic basis of a fifteenth form of LGMD which has been transmitted in an autosomal dominant fashion in a large Spanish pedigree (Spanish autosomal dominant LGMD [SAD- LGMD]). The disease locus has been mapped to a seven centimorgan region of chromosome 7q31.3-32 with a maximum two-point LOD score of 7.59 with marker D7S2519. We will attempt to reduce the size of the disease locus by fine mapping studies. Candidate genes will be screened until the disease mutation is identified. The pathogenesis of the disease will be studied by studying the expression of the gene messenger RNA and the gene product in the patients' skeletal muscle and in tissue culture using cells from patients. A mouse model of the disease will be produced to further investigate the pathogenesis. Muscle biopsies from more than 50 patients with LGMD of unknown etiology will be screened for defects of the SAD-LGMD gene product. The identification of the cause of SAD-LGMD will expand our understanding of the disease and will likely enhance our general understanding of skeletal muscle functions and structure. For the patients, achieving the proposed goals will allow more accurate prenatal diagnosis, genetic counseling, and perhaps contribute to more rational therapies in the future. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen
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Project Title: PATHOGENESIS OF EMERY-DREIFUSS MUSCULAR DYSTROPHY Principal Investigator & Institution: Worman, Howard J. Associate Professor; Medicine; Columbia University Health Sciences New York, NY 10032 Timing: Fiscal Year 2003; Project Start 15-MAY-2003; Project End 30-APR-2008 Summary: (provided by applicant): Emery-Dreifuss muscular dystrophy (EDMD) is characterized by region muscle contractures, slow progressive muscle wasting and cardiomyopathy with atrioventricular conduction block. Indistinguishable forms of EDMD are inherited in autosomal dominant and X-linked manners. Mutations in emerin, an integral protein of the nuclear envelope inner membrane, cause X-linked EDMD. Autosomal dominant EDMD is caused by mutations in the LMNA gene, which encodes the nuclear envelope intermediate filament proteins lamins A and C. It is not known how mutations in nuclear envelope proteins cause muscular dystrophy. We hypothesize that mutations in these chromatin-associated proteins cause changes in the expression of genes responsible for muscle cell differentiation or survival. Our goal is to test this hypothesis using a combination of studies in transfected cells, patients' cells and tissues and animals models. In the first specific aim, we will use fluorescence microscopy and photobleaching methods to investigate how lamin A and C mutants from patients with autosomal dominant EDMD influence the mobility of emerin in the inner nuclear membrane. We will determine if mutant lamins A and C cause emerin to "escape" from the inner nuclear membrane into the continuous endoplasmic reticulum. As patients with X-linked EDMD do not have emerin in the inner nuclear membrane, this finding would demonstrate a connection between the X-linked and autosomal dominant forms of the disease. In the second aim, we will use microarrays to compare gene expression in cells from patients with autosomal dominant EDMD to X-linked EDMD and Dunnigan-type partial lipodystrophy, a disease caused by mutations in different regions of lamins A and C. This will establish if emerin and lamin mutations responsible for EDMD alter expression of the same genes. We will also use microarrays to determine gene expression profiles in muscles from lamin A/C "knockout" mice that develop muscular dystrophy and compare the results to what is known about pathologic alterations in gene expression in Duchenne muscular dystrophy. The results will be confirmed in tissues from human subjects with EDMD. In Aim 3, we will generate transgenic mice expressing human lamin A mutants and determine if they develop pathological abnormalities of EDMD and similar gene expression changes. This work will help establish how abnormalities in the nuclear envelope cause muscular dystrophy. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen
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Project Title: PATHOGENESIS OF LAMININ-ALPHA2 DEFICIENCY Principal Investigator & Institution: Miller, Jeffrey B.; Boston Biomedical Research Institute 64 Grove St Watertown, MA 02472 Timing: Fiscal Year 2002; Project Start 19-SEP-2002; Project End 31-AUG-2006 Summary: (provided by applicant): Pathogenesis of laminin-ot2-deficiency. Mutations in the human LAMA2 gene cause congenital muscular dystrophy, group 1 (CMD 1), a devastating, recessive disease of childhood. LAMA2 encodes laminin-c Beta 2, an extracellular protein that is abundant in skeletal muscle. The proposed experiments will test hypotheses about how loss of laminin-c_2 leads to the severe neuromuscular dysfunction in CMD1. For Aims 1 & 2, we will examine the role of apoptosis in CMD1 pathogenesis. In culture, laminin-cz2-deficient myotubes are unstable and die by a process that is inhibited by the antiapoptosis protein Bcl-2. It is not known, however,
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whether apoptosis is important in the loss of CMD1 neuromuscular function in vivo. The proposed experiments willdetermine how disease in laminin-c_2-deficient mice is affected by targeted alterations of Bcl-2 family members. For Aim 3, we will determine if muscle stem cell function is altered in CMD 1. Postnatal muscle contains multipotent stem cells, but no studies have examined these recently identified stem cells in diseased muscle. We will test the possibility that laminin- Beta 2-deficiency activates proliferation and alters the differentiation capability of these rare cells. For Aim 4, we will determine if inappropriate re-entry into the cell cycle occurs in affected tissue. Inappropriate cell cycling can lead to death of normally post-mitotic cells including neurons and myofibers. We hypothesize that laminin-cz2-deficiency alters signal transmission resulting in dysregulation of the cell cycle. To test this hypothesis, we will determine if cell cycle regulators are inappropriately induced in laminin-c beta 2-deficient cells. The results will increase our understanding of CMD 1 pathogenesis and could suggest new routes to therapy, perhaps based on apoptosis inhibition, stem cell repair, or cell cycle inhibition. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •
Project Title: PATHOPHYSIOLOGY OF OCULOPHARYNGEAL MUSCULAR DYSTROPHY Principal Investigator & Institution: Thornton, Charles A.; University of Rochester Orpa - Rc Box 270140 Rochester, NY 14627 Timing: Fiscal Year 2001 Summary: This abstract is not available. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen
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Project Title: PEDIATRIC BONE GROWTH, DENSITY, AND METABOLISM Principal Investigator & Institution: Henderson, Richard C. Professor; Orthopaedics; University of North Carolina Chapel Hill Office of Sponsored Research Chapel Hill, NC 27599 Timing: Fiscal Year 2001; Project Start 30-SEP-1999; Project End 30-JUN-2004 Summary: Diminished growth, deformity, osteopenia noted on plain radiographs, and frequent osteoporosis-related fractures are evidence of problems with bone growth and metabolism in many children with an assortment of medical and physical conditions. Although these very late consequences are clinically apparent, the problems are usually initially silent during the important years of skeletal growth and development. The Midcareer Award is requested to support the Research Plan of Dr. Richard Henderson, MD, PhD. He is Professor of Orthopaedics and Pediatrics at the University of North Carolina, and in this capacity is a clinically active pediatric orthopaedic surgeon. Dr. Henderson also has a long-standing commitment to clinical research, with proven productivity. His primary research focus is on the issues of osteoporosis, fractures, and bone growth and metabolism in various pediatric conditions such as cerebral palsy, cystic fibrosis, milk allergy, chemotherapuetically treated malignancies, and muscular dystrophy. In the first phase of his Research Plan techniques for assessing bone growth, density, and metabolism are adapted to the unique features of handicapped children. The first phase also includes several single-site, observational, cross-sectional and longitudinal studies with the specific aim of assessing the potential impact of these assorted conditions on mineralization of the immature skeleton. This phase of the Research Plan has just been completed. The second phase includes projects designed to better characterize bone growth and metabolism in children with cerebral palsy, and to
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assess in greater detail the prevalence, causes, and outcomes of osteoporosis in this population. The utility of this information depends in great part on the availability of prevention and/or treatment alternatives. The bisphosphonates are a class of medications used for the treatment of osteoporosis in elderly adults, and limited anecdotal data suggest that these drugs are also effective in children. The second phase of the Research Plan includes the first controlled clinical trial assessing the safety and efficacy of these drugs in a pediatric population. Extensive collaboration with other research centers brings greater statistical power and expertise in nutrition to studies in the second phase. The second phase consists of 5 closely inter-related projects over a 2-3 year time span, and data collection recently began in April 1998. The third phase planned for the years 2001-2004 will involve larger-scale clinical trials assessing bisphosphonates for the treatment of osteoporosis in multiple pediatric conditions. The practicalities of drug treatment in clinical practice and the dose-response relationship are important issues that will be addressed in this phase. The Midcareer Award is requested to support the second and third phases of the Research Plan. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •
Project Title: PHYSIOLOGY OF RESPIRATORY MUSCLE MIRCO MECHANICS Principal Investigator & Institution: Boriek, Aladin; Assistant Professor of Medicine and Phys; Medicine; Baylor College of Medicine 1 Baylor Plaza Houston, TX 77030 Timing: Fiscal Year 2001; Project Start 01-MAR-2001; Project End 28-FEB-2005 Summary: We propose to investigate the mechanisms of force transmission in skeletal muscles. In particular, we will investigate the contribution of desmin and dystrophin, intracellular components of the membrane cytoskeleton, the membrane receptor alpha7-integrin, and the extracellular molecular merosin to force transmission in diaphragm muscle. Desmin deficiency leads to desminopathy, a rare disease. Deficiencies of dystrophin, merosin, or alpha-7-integrin lead to various form of muscular dystrophy, which are more common diseases. Lack of any of these proteins causes skeletal muscle degeneration, chronic inspiratory muscle weakness, and ultimately respiratory insufficiency that leads to respiratory failure and eventually death. The diaphragm, unlike most other skeletal muscles, is loaded biaxially in vivo. That is the diaphragm experiences loads along muscle fibers and transverse to fibers during contractile activity. This application is an initial first step towards understanding the mechanical behavior of diaphragm muscle at the cellular level. Our central hypothesis is that force transmission in the diaphragm is modulated by transverse fiber loading and mediated by the linkage of specific intra- and extracellular members of the transmembrane protein network. This hypothesis will be tested by studying spontaneous and engineered mutant mouse strains; using strains missing key elements of the transmembrane protein network, we will test the response of the biaxial mechanical properties of the diaphragm and hindlimb muscles to the absence of these proteins. The long term goals of this research program are to understand muscle force transmission in skeletal muscles at the protein level and build a detailed model of mechanical coupling in normal skeletal muscles that explains the mechanism(s) by which force is transmitted from cytoskeleton to extracellular matrix. The specific aims of this project are to determine passive mechanical properties of the mouse diaphragm and their influence on contractile function and to evaluate the role of intracellular, transmembrane, and extracellular elements on the biaxial transmission of force in the diaphragm. Using a electron microscopy and biaxial loading technique applied to whole diaphragm and limb skeletal muscles in vitro, we will test the following hypotheses at both tissue and sarcomere levels: (1) transverse stress mediates force transmission in the normal diaphragm at both
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tissue and at sarcomere levels, and both passive and contractile properties of the diaphragm are altered by the presence of transverse stress; (2) intracellular members of the transmembrane protein network, desmin and dystrophin, are essential in integrating transverse and longitudinal mechanical properties of the diaphragm, and the strength of the mechanical linkage between myofibrils and the plasma membrane is determined primarily by these proteins; and (3) the mechanical coupling between myofibrils and extracellular matrix is crucial to force transmission along and transverse to the fibers in normal skeletal muscles, and force transmission is compromised by loss of either alpha7-integrin or merosin. These aims address the mechanism(s) by which force transmission is mediated by specific cytoskeletal and extracellular proteins in skeletal muscles. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •
Project Title: POLYCYSTIN-1 INTERACTION WITH TSC-2 IN POLYCYSTIC KIDNEY DISEASE Principal Investigator & Institution: Guan, Kun-Liang; Associate Professor; University of Michigan at Ann Arbor 3003 South State, Room 1040 Ann Arbor, MI 481091274 Timing: Fiscal Year 2003; Project Start 01-SEP-2003; Project End 31-AUG-2008 Summary: Autosomal dominant polycystic kidney disease (ADPKD) is one of the most common genetic disorders in humans. In the United States, ADPKD is more common than cystic fibrosis, Huntington's disease, and muscular dystrophy. ADPKD is characterized by the formation of cysts in kidney and caused by mutation in either PKD1 (85%) or PKD2 (15%) gene. Tuberous sclerosis (TSC) is an autosomal dominant inheritable genetic disorder due to mutation in either TSC1 or TSC2 gene. TSC is characterized by formation of hamartomas in various tissues. Cyst formation in kidney is also observed in TSC. The PKD1 and TSC2 genes are located adjacent to each other on human chromosome 16p and deletion of both genes results in a contiguous gene syndrome responsible for the severe infantile polycystic kidney disease. TSC2 has been implicated to play a role in the proper functions of polycystin-1, the product of PKD1 gene. The long-term goals of this project are to understand the functional relationship between TSC2 and PKD1 and to elucidate the molecular mechanism of TSC2 in regulation of PKD1 function and ADPKD. The specific aims of this proposal are to elucidate the mechanism of TSC2 regulation by osmotic stress and to investigate the function of TSC2 in regulation of the plasma membrane localization of polycystin-1. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen
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Project Title: POSTISOPRENYLATION PROCESSING AND THE NUCLEAR LAMINA Principal Investigator & Institution: Young, Stephen G. Professor; J. David Gladstone Institutes 365 Vermont St San Francisco, CA 94103 Timing: Fiscal Year 2003; Project Start 15-SEP-2003; Project End 30-JUN-2008 Summary: (provided by applicant): The proteins of the nuclear lamina have generated enormous interest because of recent studies showing that mutations in the gene for lamin A/C (LMNA) develop a host of different diseases, including cardiomyopathy, muscular dystrophy, and partial lipodystrophy. The objectives of this proposal are to define the enzymes that are important in the posttranslational processing of the nuclear lamins and to understand the consequences of defective posttranslational processing at both the cellular and tissue levels. Prelamin A (664 amino acids) terminates with a "CAAX" sequence motif and undergoes a complicated series of posttranslational
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modifications. First, the cysteine (C) of the CAAX motif is farnesylated by protein farnesyltransferase. Second, the last three amino acids of the protein (i.e., the -AAX) are released by a prenylprotein-specific endoprotease (likely Rce1 or Zmpste24 or both). Third, the newly exposed farnesylcysteine is methylated by isoprenylcysteine carboxyl methyltransferase (Icmt), a membrane protein of the endoplasmic reticulum. Fourth, once the cell has gone to all of this effort, the carboxyl-terminal 15 residues of the protein (including the farnesylcysteine methyl ester) are clipped off and degraded, leaving mature lamin A (646 amino acids). Zmpste24 might carry out that final endoproteolyticprocessing step. Lamin B1 and B2 have a CAAX sequence motif and undergo the first three processing steps, but do not undergo a second endoproteolysis step; thus, their sequences terminate with a methylated farnesylcysteine. During the past few years, the laboratory of Dr. Stephen Young has generated knockout alleles [as well as some conditional ("floxed") alleles] for many of the genes involved in CAAX protein processing (e.g., Fntb, Rce1, Zmpste24, and Icmt) for the purpose of analyzing the importance of the posttranslational processing steps. In mice lacking Zmpste24, the processing of prelamin A to lamin A was blocked. Of note, the Zmpste24-deficient mice exhibited reduced muscle strength (suggestive of a laminopathy), and also developed spontaneous bone fractures, a peculiar finding not generally observed in humans with lamin mutations. The first aim of this grant application is to define, biochemically, the precise role(s) of Zmpste24 in prelamin A processing. The second aim is to further define the cellular and tissue pathology of Zmpste24 mice and then to determine whether all of the pathologic findings are due to defective prelamin A processing. The third aim is to understand the posttranslational processing of lamin B1 and to define the consequences of lamin B1 deficiency in mammals. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •
Project Title: POSTTRANSLATIONAL PROCESSING BY ZMPSTE24 AND LAMINOPATHY Principal Investigator & Institution: Ng, Jennifer K.; J. David Gladstone Institutes 365 Vermont St San Francisco, CA 94103 Timing: Fiscal Year 2003; Project Start 26-MAR-2004 Summary: (provided by applicant): The proteins of the nuclear lamina have generated enormous interest because missense mutations in LMNA (the gene for prelamin A, which encodes both lamin A and lamin C) cause a host of diseases, including EmeryDreifuss muscular dystrophy, limb-girdle muscular dystrophy, Charcot-Marie-Tooth type II peripheral neuropathy, and Hutchinson-Gilford progeria syndrome. Prelamin A, the precursor to mature lamin A, undergoes a series of posttranslational modifications, including the covalent attachment of a lipid to the protein, proteolytic clipping of the protein, and methylation of the protein. These post-translational modifications are important both to the targeting of the lamins to the nuclear envelope and to their function. The laboratory of my mentor, Dr. Stephen G. Young, recently identified an endoprotease, Zmpste24, that is required for the maturation of prelamin A to lamin A. Interestingly, Zmpste24-deficient mice develop a muscle weakness phenotype I strikingly similar to that observed in mice lacking lamin A/C. A key objective of my application is to define the pathological and molecular underpinnings of the possible muscular dystrophy, peripheral neuropathy and progeria phenotype in Zmpste24deficient mice, as well as compare them to mice harboring mutant Lmna alleles. Finally, I will investigate the consequences of defective posttranslational processing of lamin A on a cellular level in order to elucidate the biochemical role of Zmpste24 in prelamin A processing.
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Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •
Project Title: PROBING THE GATING MECHANISM OF SK CHANNELS Principal Investigator & Institution: Bruening-Wright, Andrew H. None; Oregon Health & Science University Portland, OR 972393098 Timing: Fiscal Year 2002; Project Start 14-SEP-2002 Summary: (provided by applicant): Small conductance calcium-activated potassium channels (SK channels) are fundamental regulators of neural excitation, important for setting interspike intervals, influencing burst firing patterns, and for their hyperpolarizing role in tonic membrane oscillations. They have been implicated in the disease myotonic muscular dystrophy, linked to memory and learning processes, and their normal expression is important for respiration and parturition. Cloning and heterologous expression of SK channels has allowed characterization of their fundamental properties, and biophysical, molecular biological, biochemical, and crystallographic techniques have proven that calcium gates SK channels entirely by an associated subunit, calmodulin (CaM). Thus the calcium-sensor CaM binds to a domain of approximately 100 residues in the C-terminus of SK, the CaMBD, and transduces its own calcium-induced structural changes to the SK channel, thereby opening and closing the channel. The CaM-CaMBD crystal structure has recently been solved in the presence of calcium, and provides an excellent model for testing how SK channels gate. Since specific interaction sites between CaM and the CaMBD are now known, stabilization of these interactions can distinguish regions of the complex that must move in order for the channels to gate. By determining how SK channels move during gating, insight will be gained into the molecular movements that underlie the function of this important class of ion channel. A fundamental understanding of SK gating has implications for all calcium-gated ion channels, with potential biomedical applications such as the design of drugs which modulate SK gating. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen
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Project Title: PROGRAM PROJECT GRANT Principal Investigator & Institution: Uitto, Jouni J. Dermatology/Cutaneous Biology; Thomas Jefferson University Office of Research Administration Philadelphia, PA 191075587 Timing: Fiscal Year 2002; Project Start 15-AUG-1987; Project End 31-MAR-2007 Summary: This renewal application proposes extensive and innovative studies focusing on the molecular genetics of the cutaneous basement membrane zone (BMZ) towards delineating the molecular basis of various forms of epidermolysis bullosa (EB) and other selected genodermatoses affecting the epidermis. The proposed studies are designed to test the hypothesis that genetic lesions in structural genes expressed in the epidermis underlie variants of these diseases, and that the precise phenotype and mode of inheritance depend on the types and combinations of specific mutations in distinct genes. This application is based on solid progress in this project, including (a) expansion of the molecular basis of the recessive dystrophic forms of EB allowing refinement of genotype/phenotype correlations; (b) identification of novel and de novo COL7A1 mutations in dominant DEB, with an impact on genetic counseling of the families at risk of recurrence; (c) identification of a large number of novel and recurrent mutations both Herlitz and non-Herlitz junctional EB; (d) identification of uniparental disomy of chromosome 1 as a novel mechanism for H-JEB; (e) demonstration in mutations in the genes ITGA6 and ITGB4 encoding alpha-6-beta-4 integrins subunit polypeptides in EB
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with pyloric atresia,; (f) cloning of the human plectin gene and demonstration of mutations in EB with late-onset muscular dystrophy; (g) cloning of mouse type VII collagen and desmoglein 3 genes with development of "knock-out" mice with blistering phenotype; (h) identification and characterization of several novel genes expressed into the epidermis, including periplakin, ladinin, and desmo-15; (i) refinement of RNADNA chimeric oligonucleotide technology for repair of the mutated genes in heritable skin diseases. This proposal details continuation of concentrated, multi-disciplinary studies in five highly interdependent projects: Project 1, "Molecular Genetics of EB and Other Heritable Disorders of the Cutaneous BMZ and Epidermis," will provide precise information on the specific mutations in the gene/protein system that are at fault in various forms of EB and other epidermal heritable disorders. Project 2, "Identification and Characterization of Candidate Genes/Protein Systems Expressed in the Skin," will provide new gene probes and information about novel genes as potential candidate genes for epidermal genodermatoses. Project 3, "Consequences of the Mutations at the Protein Structure/Function Level" will examine the structural and functional alterations that result from distinct mutations in the candidate genes, utilizing computer modeling and monitoring functional interactions in biosensor analysis system. Project 4, "Development and Testing of Animal Models for EB," will generate novel animal models for EB. Project 5, "Development of Non-Viral Gene Therapy for Cutaneous Diseases," will concentrate on testing gene therapy approaches utilizing RNA/DNA chimeric oligonucleotide strategies. These multidisciplinary studies are expected to provide precise information of critical importance for translational applications towards development of refined classification, genotype/phenotype correlations, basis for genetic counseling, and prenatal testing, as well as providing the basis for novel gene therapy approaches for this devastating group of skin diseases. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •
Project Title: PROPERTIES CHROMATIUM VINOSUM
OF
MOLECULAR
CHAPERONES
FROM
Principal Investigator & Institution: Torres-Ruiz, Jose A. Associate Professor; Ponce School of Medicine G.P.O. Box 7004 Ponce, PR 00731 Timing: Fiscal Year 2001; Project Start 30-SEP-1986; Project End 31-MAY-2005 Description (provided by applicant): One of the most challenging problems in Cell Biology is to understand the mechanisms by which Molecular Chaperones assist protein folding in nature. These mediators have been implicated in a wide range of fundamental biological events including; preventing formation of proteinaceous aggregates, promoting assembly and/or disassembly of oligomeric enzymes, and aiding in the protein translocation process. The emerging evidence suggests that Chaperones are ubiquitous and there is intensive interest in unraveling the precise molecular events by which this class of proteins functions at the cellular level. Moreover, recent studies conclusively demonstrate that the etiology of a variety of pathological conditions could be explained based in alterations in the expression and function of Molecular Chaperones. For instance, alterations in the expression and activation of these mediators have been convincingly demonstrated in the development of autoimmune diseases, viral and bacterial infections, cancer, and muscular dystrophy. During the last few years, we have been able to identify and biochemically characterize three Chaperones, Cpn60, Cpn10 and Hsp70 from the bacterium C. vinosum, and more. Recently, we been have successful in identifying other Chaperone systems, from the same organism, which appear to be homologs of the DnaJ, GrpE and ClpB families. Some of these mediators suffer phosphorylation and, in the present application we intend to obtain information
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in regards to the biological significance of this finding. The hypothesis to be tested in this proposal is that the ability of Chromatium vinosum Cpn60 in modulating protein folding events is controlled by protein phosphorylation and by its direct physical interaction with other Molecular Chaperones. This hypothesis will be tested by pursuing the following specific aims: (1) to evaluate the influence of various Molecular Chaperone Systems; DnaK, GrpE, DnaJ, Cpn10 and CIpB, in modulating the autophosphorylation of Cpn60 from C. vinosum; (2) to study the ability of Cpn60, in combination with other Chaperone systems, to favor disaggregation and refolding of denatured proteins; (3) to study the intracellular location of various Chaperone systems from C. vinosum, namely DnaK, DnaJ, GrpE, ClpB, and Cpn60/Cpn10, under heat shock and other stressful conditions; (4) to study the conditions that favor the Cpn60 binding to the cytoplasmic membranes of C. vinosum; (5) to study the properties of phosphorylated Cpn60 from C. vinosum under heat shock conditions and; (6) to study the impact of the Cpn60 catalyzed phosphorylation on the functional properties of RuBisCO. Results from these experiments promise to advance our understanding on the mechanisms by which Chaperones modulate protein folding. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •
Project Title: REGULATION OF SKELETAL MUSCLE REGENERATION Principal Investigator & Institution: Li, Yi-Ping; Medicine; Baylor College of Medicine 1 Baylor Plaza Houston, TX 77030 Timing: Fiscal Year 2003; Project Start 01-JUL-2003; Project End 30-JUN-2008 Summary: (provided by applicant): Tumor necrosis factor-alpha (TNF-alpha) is traditionally recognized as a circulating mediator that stimulates muscle catabolism in inflammatory diseases. However, recent discoveries indicate that TNF-alpha plays a more complex and more fundamental role in skeletal muscle. It is now clear that skeletal myocytes constitutively express TNF-alpha. Biological processes that demand myofiber regeneration - degenerative muscle diseases (inflammatory myopathies and Duchenne muscular dystrophy), injury and exercise -- accelerate TNF-alpha expression by myocytes. Further, it is increasingly evident that TNF-alpha is critical for muscle regeneration because it accelerates myogenic gene expression. Based on growing evidence from our and other laboratories, we propose that TNF-alpha functions as an autocrine/paracrine modulator of muscle regeneration by promoting the expression of adult-type muscle proteins during early differentiation via activating MADS-box myogenic factors, MEF2 and SRF, and a muscle hypertrophy mediator GATA-2. Three specific aims will be pursued to test this model. Aim 1. To evaluate upregulation of TNF-alpha as an autocrine modulator of primary myoblast differentiation. TNF-alpha expression during differentiation induced by distinct stimuli (serum restriction, cell confluence and cyclic stretch), and effects of TNF-alpha on adult-type muscle protein expression during differentiation will be determined in rat and mouse primary myoblasts. Aim 2. To determine whether TNF-alpha promotes muscle regeneration in vivo. Effects of TNF-alpha deficiency on muscle regeneration evoked by cardiotoxininduced muscle injury will be evaluated in mice with genetic or immunological blockade of TNF-alpha receptors. Muscle histology, contractile force generation, and myogenic gene expression will be determined to evaluate regeneration. Aim 3. To determine signaling events by which TNF-alpha stimulates myogenic differentiation. TNF-alpha stimulation of MEF2, SRF, and GATA-2, and the underlying signaling mechanisms will be evaluated. Our long-term objectives are to understand the role of cytokines as an emerging group of muscle regeneration modulators, and to improve the treatment of degenerative muscle diseases.
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Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •
Project Title: REGULATION OF UTROPHIN PROMOTER IN MUSCLE Principal Investigator & Institution: Khurana, Tejvir S. Assistant Professor; Physiology; University of Pennsylvania 3451 Walnut Street Philadelphia, PA 19104 Timing: Fiscal Year 2003; Project Start 15-MAY-2003; Project End 30-APR-2008 Summary: (provided by applicant): Utrophin (dystrophin related protein) shares extensive sequence homology and organizational motifs with dystrophin, and is considered to be the autosomal homolog of dystrophin. Indeed, transgenic over expression of utrophin can functionally substitute for the missing dystrophin molecule and reverse the dystrophic patho-physiology in the muscles of mdx (dystrophic) mice. The utrophin gene, while ubiquitously expressed, has a highly regulated sub-cellular distribution during development, regeneration as well as in mature skeletal muscle. In mature myofibers (elongated multi-nucleated cells), utrophin is enriched at the synapse or neuromuscular junction (NMJ). The spatial distribution of utrophin in myofibers parallels the distribution of nicotinic acetylcholine receptors (nACHR) to a remarkable degree, in particular, the manner in which they are influenced by the release of growth and differentiation factors (e.g. heregulin) from motor nerves. Selective enrichment of nACHR and utrophin at the NMJ occurs, in part, due to their messages being preferentially transcribed at sub-synaptic nuclei rather than nuclei scattered along the length of the myofiber. We and others, recently demonstrated that the neurite-associated growth factor heregulin utilizes the ERK (MAP kinase) signaling pathway to promote the binding of the GABPa/b transcription factor complex to the N-Box motif of the utrophin promoter, thus activating the promoter and increasing utrophin gene expression in cultured muscle cells. Current hypotheses on the regulation of utrophin expression in muscle center on N-box dependent compartmentalized transcription of utrophin at sub-synaptic nuclei. We hypothesize that additional trans-acting factors exist and regulate the utrophin promoter. We also hypothesize that co-operability among these trans-acting factors and signaling pathways plays a role in utrophin promoter regulation. In our preliminary studies, we have identified additional transacting factors, their signaling pathways and describe their co-operability in utrophin promoter regulation; we have also studied heregulin mediated utrophin promoter activation in mouse muscle, in vivo. In this proposal we plan to extend these studies to better understand the molecular mechanisms of utrophin promoter regulation in skeletal muscle. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen
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Project Title: RES FACIL: MUSCULAR DYSTROPHY Principal Investigator & Institution: Roth, Paul B. Clinical Research Center; University of New Mexico Albuquerque Controller's Office Albuquerque, NM 87131 Timing: Fiscal Year 2002; Project Start 15-SEP-2002; Project End 14-SEP-2003 Summary: (provided by applicant): The UNM is requesting funds to construct a new building to house several key neuroimaging modalities magnetic resonance imaging (MRI), Electron Paramagnetic Resonance (EPR), magnetoencephalography (MEG) and electroencephalography (EEG), plus a Cellular and Molecular Biology core, so that the investigators can carry out a truly multimodal neuroimaging research on the same animals. This building is planned as the animal component of a comprehensive neuroimaging facility that will also include an expanded facility (whole-head MEG and EEG, high-field MRIs) for human research. The funding in 2001 from the Institutional
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Development Award (IDeA) program [1P20RR15636, Principal Investigator (PI), Dr. Yoshio Okada] has generated an enormous level of enthusiasm at the UNM. The IDeA funding has enabled UNM to purchase several key pieces of imaging equipment (4.7T MRI, EPR and 2-photon microscope) that can be combined with the existing set of equipment for MEG, EEG and the supporting Cellular and Molecular core to carry out a multimodal neuroimaging research. These imaging modalities will be all housed in the proposed building. The physical proximity of the core facilities will enable UNM researchers to produce unique results that will provide the edge necessary to be competitive at the national level for National Institutes of Health (NIH) funding. This will be crucial for building a long-term research program that will be competitive for many years to come, beyond the five-year funding period (2/2001-1/2006) of the UNM COBRE. The UNM is providing $1,065,373 to support this application. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •
Project Title: RESCUE ANALYSIS OF UTROPHIN & NMJ SUPPORT BY SYNTROPHIN Principal Investigator & Institution: Sealock, Robert W. Associate Professor; Cellular/Molecular Physiology; University of North Carolina Chapel Hill Office of Sponsored Research Chapel Hill, NC 27599 Timing: Fiscal Year 2003; Project Start 30-SEP-2003; Project End 30-JUN-2007 Summary: (provided by applicant): The syntrophins are a family of peripheral membrane adapter proteins that function in association with dystrophin, utrophin, and the dystrobrevins, all of which are proteins of the surface membrane of skeletal muscle and implicated in the important human disease, Duchenne muscular dystrophy (DMD). Alpha-syntrophin is the major syntrophin in muscle. In the alpha-syntrophin knockout mouse, the postsynaptic membrane at the neuromuscular junction shows major biochemical and morphological defects including low amounts of acetylcholine receptors and acetylcholinesterase, a complete absence of utrophin, immature appearing contacts, junctional folds that are disorganized and few in number, and altered distribution of AChR. Thus, there is a utrophin and NMJ support function of alphasyntrophin. The first two aims of the project are to intended to extend current understanding that the other syntrophins of muscle (beta1, beta2, and probably gamma2) are not redundant with alpha-syntrophin. They are: 1) Test the hypothesis that transgenically expressed beta 1-syntrophin will restore utrophin to adult alphasyntrophin 4- junctions but will not rescue other, or all other, aspects of the phenotype. 2) Test the hypothesis that transgenically expressed beta 2-syntrophin will restore no aspects of the alpha-syntrophin -/- phenotype. The results will provide a solid framework for molecular analysis of the mechanisms of the support function. Aim 3) Identify the critical functional domains of the alpha-syntrophin molecule by transgenic expression in alpha-syntrophin -/- mice of a) chimeric proteins containing domains of beta substituted into alpha-syntrophin (or the converse, alpha into beta) and/or b) alpha-syntrophin specifically mutagenized at selected sites. The results will identify domains and implicate syntrophin-dependent pathways. Aim 4) Determine whether low levels of utrophin mRNA, inability of the membrane to accept utrophin incorporation, or both contribute to the lack of utrophin at alpha-syntrophin -/- NMJs. If applicable, use these tools to analyze the transgenic mice. 5) Seek to identify determinants in the AChR accumulation pathway-- AChR mRNA levels, total AChR expression, cell surface AChR expression, AChR clustering response to agrin, stability of agrin-induced clusters--that may contribute to the low AChR content of alpha-
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syntrophin 4- NMJs. If applicable, use the understanding so generated to analyze the transgenic mice. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •
Project Title: RNA DOMINANCE IN HUMAN DISEASE Principal Investigator & Institution: Swanson, Maurice S. Associate Professor; Molecular Genetics & Microbiol; University of Florida Gainesville, FL 32611 Timing: Fiscal Year 2001; Project Start 01-APR-2000; Project End 31-MAR-2005 Summary: (appended verbatim from investigator's abstract): Myotonic dystrophy (DM) is the most common form of adult onset muscular dystrophy. DM is an autosomal dominant neuromuscular disorder that is caused by a (CTG)n repeat expansion in the 3' UTR of the DM protein kinase (DMPK) gene. The long term objective of the proposed research is to elucidate how a triplet repeat expansion in the 3' UTR of a gene leads to a dominantly inherited disease. Current evidence suggests that DM pathogenesis is associated with the accumulation of DMPK mutant allele transcripts within the nucleus. Our working 'sequestration' hypothesis is that DM is an RNA dominant disease in which the (CUG)n expansion forms an exceptionally stable double stranded RNA (dsRNA) hairpin structure. This unusual RNA hairpin acts as a high affinity binding site for triplet repeat expansion dsRNA binding proteins that possibly play important roles in nucleocytoplasmic RNA export. Large repeat expansions associated with severe disease lead to sequestration of these proteins on DMPK mutant allele transcripts and a dominant negative effect on the export of other RNAs. This proposal is focused on testing this RNA dominance model using several different experimental approaches. First, the hypothesis that (CUG)n expansion RNAs have a dominant negative effect on mRNA export will be directly examined using RNA microinjection into frog oocyte and mammalian fibroblast nuclei. Second, the sequestration hypothesis predicts that expansion binding proteins should accumulate in nuclear foci together with DMPK mutant transcripts. Therefore, we will complete the characterization of several proteins that preferentially recognize large (CUG)n expansions, and determine the subcellular distribution of these proteins in normal and DM patient cells. Third, preferred RNA binding sites for these expansion binding proteins will be characterized by in vitro and in vivo analyses with particular emphasis on identifying RNAs that normally associate with these proteins. Fourth, we will determine if expansion binding proteins are involved in mRNA export by combining the use of monoclonal antibodies and recombinant proteins with the microinjection system developed in the first aim. Fifth, the relevance of RNA dominance to other neuromuscular and neurological diseases will be investigated. These studies have important implications for elucidating molecular mechanisms involved in DM pathogenesis and cellular strategies which facilitate the exchange of genetic information between the nucleus and cytoplasm. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen
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Project Title: RNA/PROTEIN REGULATION
INTERACTIONS
IN
PREMRNA
SPLICING
Principal Investigator & Institution: Singh, Ravinder; Molecular, Cellular & Dev Biol; University of Colorado at Boulder Boulder, CO 80309 Timing: Fiscal Year 2001; Project Start 01-AUG-1999; Project End 31-JUL-2004 Summary: Sex determination is a fundamental decision that essentially all metazoans encounter during their development. Sex determination in Drosophila melanogaster involves a hierarchy of alternative splicing decisions, and is also the best understood
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example of splicing regulation. Splicing is a process by which non-coding sequences (introns) are removed from the precursor messenger RNA. In higher eukaryotes, constitutive and alternative splicing are important aspects of gene regulation in many important cellular processes. Approximately 15 percent of the mutations that have been linked to human diseases affect RNA splicing signals, including cellular transformation, Duchenne muscular dystrophy, and tumor metastasis. Our goal is to understand how RNA-binding proteins recognize target RNAs and regulate constitutive and alternative pre-mRNA splicing. The Drosophila protein Sex-lethal (SXL) acts as a key binary switch between the male and female cell fates. In the past, we defined the mechanism by which SXL regulates alternative splicing by antagonizing the known splicing factor U2AF65. Specificity is an underlying theme in biological regulation. U2AF65 and SXL offer excellent models for specific RNA-protein interactions in the context of splicing regulation. For example, while the general splicing factor U2AF65 recognizes a wide variety of polypyrimidine-tract/3' splice sites, the highly specific splicing repressor SXL recognizes a specific sequence. Although both proteins contain a ribonucleoproteinconsensus motif, they have distinct RNA-binding specificity. However, it is not understood how these seemingly similar proteins achieve unique RNA-binding specificities. To define the structural basis for the RNA-binding specificities of U2AF65 and SXL, we will extend our analysis of the RNA and the proteins by using a combination of biochemical, molecular, and genetic approaches. Our findings will also be directly applicable to other members of this largest family that likely regulate different aspects of RNA biogenesis. In addition, SXL controls many female-specific functions. However, some of the relevant genes that are regulated by SXL remain to be identified. To identify these targets, we will use a combination of recently developed molecular approaches - genomic SELEX and subtractive hybridization/differential display. These approaches should complement genetic analysis. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •
Project Title: ROLE OF ELAV IN NEURONAL RNA PROCESSING Principal Investigator & Institution: White, Kalpana P. Professor; Brandeis University 415 South Street Waltham, MA 024549110 Timing: Fiscal Year 2002; Project Start 10-SEP-2002; Project End 31-JUL-2007 Summary: (provided by applicant): The long-term goal of this research project is to understand how differentially-expressed trans-acting factors in neurons can control premRNA processing to precisely regulate neuronal gene expression. The powerful genetics, molecular biology and transgenic techniques of Drosophila, along with the emergent DNA microarray technology, will be utilized to study the role of ELAV in mRNA processing and its overall impact on gene expression in neurons. ELAV is the founding member of the ELAV/Hu family of RNA-binding proteins, which is conserved in both vertebrates and invertebrates. Members of the ELAV/Hu family serve diverse roles in mRNA processing, including splicing, stability and translatability. The aims of the project are: (1) elucidation of mechanisms of ELAV's interactions with RNA transcripts, (2) identification of direct targets of ELAV using immunoprecipitated ELAVribnucleoprotein complexes and DNA microarrays, (3) assessment of the overall impact of ELAV on gene expression using microarray technology. Together, these approaches will begin to identify networks of genes that are regulated collectively and provide a comprehensive view of how post-transcriptional regulation is utilized in neuronal gene expression. Given the evolutionary conservation between Drosophila and human genomes, insights in regulatory strategies will be directly transferable to human studies. Human members of the ELAV/Hu family have been implicated in pathogenesis of
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paraneoplastic cerebellar dysfunction. RNA processing defects have been documented in a large number of human diseases and inherited disorders including cancer, muscular dystrophy and fragile X syndrome. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •
Project Title: ROLE OF THE ALPHA 7 BETA 1 INTEGRIN IN MUSCLE INTEGRITY Principal Investigator & Institution: Kaufman, Stephen J. Professor; Cell and Structural Biology; University of Illinois Urbana-Champaign Henry Administration Bldg Champaign, IL 61820 Timing: Fiscal Year 2001; Project Start 24-JAN-1997; Project End 31-AUG-2006 Summary: (provided by applicant): The proper association of muscle fibers with laminin in the extracellular matrix is essential for normal muscle function. The alpha7Beta1 integrin and the dystrophin-glycoprotein complex both bind laminin and appear to be complementary linkage systems between fibers and the extracellular matrix. Congenital and acquired defects in the dystrophin-glycoprotein complex underlie the pathology associated with Duchenne and other muscular dystrophies, as well as cardiomyopathies. Mutations in the human alpha7 gene cause an additional myopathy. We recently discovered that enhanced expression of the alpha7 integrin mediated linkage system can compensate for the absence of the dystrophin-glycoprotein complex. Dystrophin/utrophin null mice develop an acute muscular dystrophy and die prematurely. Enhanced expression of the alpha7 integrin inhibits the development of muscular dystrophy and restores longevity to these animals. We propose to expand on this result and determine the level of alpha7Beta1 integrin that best prevents development of skeletal muscle pathology in these animals and whether transgene expression in the heart and smooth muscle can prevent cardiovascular disease. We will also analyze whether enhanced expression of the alpha7 integrin in the heart reduces development of cardiomyopathy associated with enterovirus-induced cleavage of dystrophin. Additional skeletal muscle and cardiomyopathies result from other defects in the dystrophin-glycoprotein linkage system. We will use transgenic animals that over-express the alpha7Beta1 integrin in different genetic backgrounds to determine whether the integrin can prevent these myopathies. Whereas mutations in the sarcoglycan genes perturb the dystrophin-glycoprotein transmembrane linkage system and cause cardiomyopathy and muscular dystrophy, we will determine whether overexpression of the alpha7 integrin can inhibit the development of muscle disease in sarcoglycan deficient mice. Likewise, we will assess whether enhanced integrin expression will ameliorate alpha2-laminin congenital muscular dystrophy. Lastly, experiments are proposed that aim at understanding the mechanism by which enhanced integrin expression inhibits development of muscle pathology. This research will reveal whether increasing alpha7 integrin levels in humans may be worth pursuing in the future as treatments for Duchenne and other muscular dystrophies and cardiomyopathies. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen
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Project Title: SARCOLEMMA IN FSHD Principal Investigator & Institution: Bloch, Robert J. Professor; Physiology; University of Maryland Balt Prof School Baltimore, MD 21201 Timing: Fiscal Year 2001; Project Start 30-SEP-2001; Project End 31-AUG-2004 Summary: (provided by applicant): Facioscapulohumeral Muscular Dystrophy (FSHD) affects 1 of every 20,000 adults in this country. FSHD has been linked to deletions at the
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telomeric region of chromosome 4 (4q35-4q35ter), and is inherited as a dominant trait. Although we have learned a great deal about the genetic defects that lead to FSHD, we still know very little about the effects these defects have at the level of individual muscle fibers. Indeed, the cell biological changes that result in muscle weakness and myofiber degeneration have never been studied. Here we propose to address this issue by examining human biopsied materials using ultrastructural techniques and immunofluorescence coupled with confocal laser scanning microscopy. We postulate that, like other human dystrophies, such as Duchennes, Beckers, and some limb girdle muscular dystrophies, the sarcolemma of FHSD muscle is altered in ways that lead to muscle weakness and ultimately to muscle degeneration. In support of this hypothesis, our preliminary studies show that the sarcolemma of FSHD muscle has frequent interruptions in its membrane skeleton, is separated from the nearest myofibrils by a considerable gap, and is organized irregularly, and most closely resembles the sarcolemma of slow twitch muscle fibers although the myoplasm is rich in fast twitch myosin. We propose to pursue three aims in our exploratory studies of FSHD muscle that will: (i) test the validity of these observations and to extend them, if possible; (ii) compare them to other human muscular dystrophies; and (iii) study the biomechanical properties of the sarcolemma, to learn if they are compromised by FSHD. Our final aim will: (iv) examine the sarcolemma of the myd mouse, which has been proposed as a possible animal model of FSHD. Our laboratory has developed an unique set of methods and antibodies that permit us to examine the overall organization of the sarcolemma and its relationship to the nearby contractile apparatus. In the past year, we have adapted these methods for use with snap frozen biopsies of human skeletal muscle. We therefore anticipate making significant progress in understanding the cell biological changes that occur in FSHD skeletal muscle, and in determining which, if any, of these changes are related to the pathophysiology of FSHD. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •
Project Title: SATELLITE STEM CELL BIOLOGY Principal Investigator & Institution: Booth, Frank W. Professor; Veterinary Biomedical Sciences; University of Missouri Columbia 310 Jesse Hall Columbia, MO 65211 Timing: Fiscal Year 2001; Project Start 15-APR-2000; Project End 31-MAR-2004 Summary: (Adapted from the applicant's abstract): Satellite cells are muscle-specific stem cells that function to repair damaged myofibers and provide new myonuclei for muscle enlargement. Rosenblatt has shown that knocking out the proliferative capacity of satellite cells prevents hypertrophy of skeletal muscle. Blau and Wright have found that satellite cells prematurely senesce in young patients with Duchenne's muscular dystrophy who have many cycles of regeneration. Schultz has observed a progressive loss of the proliferative capacity of satellite cells as rats age, and similar data has just been reported in humans. Hayflick showed that normal, diploid cells have a finite proliferative lifespan and reach cellular senescence. However, Bischoff indicated that a critical evaluation of the self-maintenance criteria required to categorize the satellite cell as stem cell is yet to be undertaken. These provocative reports highlight some of the conceptual framework to pose the following specific aims. Using the well-established and validated approach of clonogenecity assays to determine a cell's proliferation potential, this proposal examines 1.) whether a physiological model of repeated cycles of atrophy-regrowth in old skeletal muscle speeds satellite cells to senescence so that their proliferative capacity is depleted prior to the lifespan of rats; 2.) determine whether the application of IGF-1 to skeletal muscle or 3.) increased contractile activity, or both aims 1 and 2 results in either a.) using up or b.) replenishing the finite population doublings in
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old satellite cells. These results would shed much needed insight into whether replicative senescence can be modulated by environmental factors. The information thus gleaned from these studies will provide the basis for follow-up experiments that will measure cell cycle markers to begin to explain the observations in molecular detail. As the number of individuals with frailty is rapidly increasing, it becomes a more urgent clinical, social, and economic issue to find out if and how satellite cell lifespan can be maintained/enhanced. This proposal will therefore provide novel insights into how the self-maintenance properties of satellite cells is modulated by compensatory factors (IGF1 and exercise), thereby forming the basis for more effective interventions against senileatrophy and frailty. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •
Project Title: SFT FUNCTION AND REGULATION IN HEMOCHROMATOSIS Principal Investigator & Institution: Wessling-Resnick, Marianne; Professor; Nutrition; Harvard University (Sch of Public Hlth) Public Health Campus Boston, MA 02460 Timing: Fiscal Year 2001; Project Start 15-SEP-1999; Project End 31-AUG-2004 Summary: Hereditary hemochromatosis is a genetic disorder that promotes increased intestinal absorption and progressive tissue deposition of iron resulting in cirrhosis of the liver, hepatic carcinoma, congestive heart failure, endocrinopathies and premature death. It is estimated that 1 in 200-to-400 people in the US are homozygous for this disease which is the most common defective genetic trait known in humans, more prevalent than cystic fibrosis, phenylketonuria and muscular dystrophy combined. Iron assimilation is a tightly regulated process that is limited to prevent harmful effects due to overload of this toxic metal and therefore a reciprocal relationship exists between body iron stores and dietary iron absorption, although the molecular basis for ion homeostasis remains unknown. Many studies of the molecular basis for hemochromatosis have evaluated the expression of factors involved in iron metabolism , including transferrin, transferrin receptor, ferritin and IRPs, but strong evidence to support their abnormal regulation in this disease is lacking. We recently identified SFT (Stimulator of Fe Transport) as a facilitator of non-transferrin-bound iron uptake. Our preliminary results demonstrate that SFT expression is down- regulated at both the mRNA and protein level in response to iron-loading. However, in the course of these studies, we made the significant discovery that SFT mRNA is 5-fold higher in liver from hemochromatosis patients despite the deposition of iron that occurs in this tissue. Thus, our working hypothesis is that malregulated expression of SFT contributes to the etiology of hemochromatosis. The proposed research will specifically evaluate our hypothesis through the following goals: 1) determination of SFT activity in iron transport by hepatocytes and intestinal enterocytes; 2) examination of interactions of interactions with the hemochromatosis protein Hfe that may modulate SFT expression and function in these cells; and 3) characterization of the mechanism that regulates SFT expression. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen
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Project Title: SIGNAL TRANSDUCTION MECHANISMS IN THE NERVOUS SYSTEM Principal Investigator & Institution: Chao, Moses V. Professor; Cell Biology; New York University School of Medicine 550 1St Ave New York, NY 10016 Timing: Fiscal Year 2001; Project Start 01-JUL-1999; Project End 30-JUN-2004
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Summary: This application is for a new training program in the mechanisms of signal transduction in the nervous system at New York University Medical Center. The training faculty include fifteen distinguished scientists representing the Departments of Physiology and Neuroscience, Pharmacology, Microbiology Biochemistry and Cell Biology. The research interests of the program faculty encompass a broad range of fields, including growth factors, cytokines, chemokines, neurotrophic factors and the mechanisms by which extracellular and intracellular signals are transduced; cell adhesion molecules that influence neuronal axonal pathfinding and process outgrowth; selection of synaptic targets; ion channel function; and processes that lead to axonal-glial cell communication. The purpose of this program is to foster the training of graduate students and postdoctoral fellows in basic mechanisms by which neuronal, glial and neuromuscular structure and function are determined. The underlying theme of the program is that cell specification and function in the nervous system are dependent upon ligand-receptor interactions and activation of second messenger pathways. Based upon a record of productive interactions, research collaborations among the trainees and between the participating faculty will be fostered. Trainees will participate in activities including weekly seminars and journal clubs in cellular and developmental neurosciences, journal clubs, and meetings that are designed to provide a broad educational exposure. The emphasis in this training program will be on fundamental biochemical and cellular mechanisms, which are relevant to disorders of the nervous system, including Alzheimer's disease, Parkinson's disease, paralysis, multiple sclerosis and muscular dystrophy. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •
Project Title: SK CHANNELS IN HYPEREXCITABLE SKELETAL MUSCLE Principal Investigator & Institution: Adelman, John P. Senior Scientist; None; Oregon Health & Science University Portland, OR 972393098 Timing: Fiscal Year 2001; Project Start 01-APR-1998; Project End 31-MAR-2002 Summary: Skeletal muscle excitation is normally controlled by the influence of innervating nerve. However, prior to innervation, upon denervation, in patients with myotonic muscular dystrophy (DM), or myotubes cultured in the absence of nerve, skeletal muscle is hyperexcitable, in that a train of action potentials is often induced following an evoked contraction. The cellular hallmark of these conditions is the appearance of receptors for the peptide toxin apamin, a potent blocker of small conductance calcium-activated potassium (SK) channels. Indeed, application of apamin to denervated or myotonic dystrophic skeletal muscle dramatically repress the hyperexcitability, demonstrating that SK channels are central to the hyperexcitable state. We have cloned the apamin sensitive SK channels from skeletal muscle, SK3, and found that upon denervation or after differentiation of the muscle cell line, L6, the SK3 gene is expressed while in normally innervated muscle it is not expressed. Neither the physiological role of SK channels in hyperexcitable skeletal muscle nor the molecular cues controlling SK3 gene expression are yet understood. In this proposal, we will test the hypothesis that: (1). SK3 channels reside in the transverse tubules of denervated skeletal muscle cells. Patch clamp measurements will be performed using denervated normal and detubulated cultured myotubes. Immunohistochemistry using SK3 channelspecific antibodies, and I125-apamin binding studies will be performed. (2). SK channel activity induces hyperexcitability. Skeletal muscle myotubes and nerve cells will be cocultured. SK channels will be heterologously expressed by infection with recombinant retroviruses and the cells electrophysiologically assayed. (3). The SK3 promotor is activated following differentiation of cultured L6 myoblasts. a) SK3 promotor/luciferase
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constructs will be introduced into L6 myoblasts, and luciferase activity assessed before and after differentiation; b) gel-shift and footprint assays will be performed with nuclear extracts from pre- and post-differentiated L6 cells; c) previously uncharacterized sequences in the SK3 promotor shown to be necessary for activation following myoblast differentiation will be used to screen a differentiated L6 skeletal muscle cDNA expression library. (4). DMAHP (myotonic dystrophy associated homeodomain protein or DMPK (myotonic dystrophy protein kinase) regulates SK channel expression. a) DMAHP and/or DMPK will be ectopically expressed in L6 myoblasts and SK3 mRNA and channel activity assessed before and after differentiation. b) gel-shift assays and footprints will be performed with the SK gene promotor and recombinant DMAHP; c) SK3 promoter/luciferase constructs will be introduced with or without DMAHP and/or DMPK into L6 myoblasts and the promoter elements responsible for regulation will be determined. These studies will establish a framework for understanding the molecular, cellular and physiological abnormalities of hyperexcitable skeletal muscle as well as the coordinate regulation of SK gene expression in muscle tissue. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •
Project Title: SKELETAL MUSCLE STRUCTURE AND FUNCTION IN AGING MDX MICE Principal Investigator & Institution: Brooks, Susan V.; University of Michigan at Ann Arbor 3003 South State, Room 1040 Ann Arbor, MI 481091274 Timing: Fiscal Year 2001 Summary: The purpose is to investigate the function of dystrophin and the dystrophinassociated proteins (DAPs) in skeletal muscle fibers and how defects in the dystrophinDAP complex contribute to the pathological changes in muscle over the life span of mdx mice. The absence of dystrophin from the muscles of patients with Duchenne muscular dystrophy leads to ongoing muscle fiber degeneration, progressive necrosis, and fibrosis. Dystrophin is also absent from the muscles of mdx mice. The mechanisms underlying the degenerative process in dystrophic muscle are unknown, but replacement of dystrophin in transgenic-mdx mice prevents many of the dystrophic symptoms. In control animals, degeneration of myofibers may result from contractioninduced injury and susceptibility to contraction-induced injury than those in agematched control mice, but for muscles in transgenic-mdx mice the susceptibility to injury is not known, nor has the effect of age on contraction-induced injury been studied in mdx or transgenic mdx-mice. The working hypothesis are that (i) the dystrophin-DAP complex shunts contractile forces laterally from the myofibrils through the plasma membrane to the extracellular matrix, and a lack of dystrophin results in stress concentrations on the sarcolemma which damage the membrane, and a mechanically compromised cytoskeleton which increases sarcomere heterogeneity and damage; and (ii) the increased susceptibility to both sarcolemma and sarcomere damage is aggravated as animals age. Specific hypotheses have been formulated regarding the mechanical function of dystrophin and the effects of age on contraction- induced injury of dystrophic muscle fibers. Structure/function relationships of the dystrophin-DAP complex will be studied in single intact fibers from muscles of control, mdx, and transgenic-mdx mice, and contraction-induced injury will be studied using single fibers in vitro and whole muscles in situ from adult and old mice. Determining the function of dystrophin and why its absence is so devastating will contribute significantly to out understanding of the mechanisms underlying the wasting and weakness that occurs with dystrophy and with normal aging. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen
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Project Title: SPIRITUALITY OF CHILDREN WITH DMD Principal Investigator & Institution: Pehler, Shelley-Rae; None; University of Iowa Iowa City, IA 52242 Timing: Fiscal Year 2003; Project Start 14-MAR-2004 Summary: (provided by applicant): This application proposes research to explore the spirituality of an 8 -12 year old child with Duchenne Muscular Dystrophy. Duchenne Muscular Dystrophy (DMD) is a progressive, genetically inherited, chronic disease with a life-threatening prognosis. Early confirmation of the type of genetic disease a child has allows interventions to be initiated that may affect the quality and longevity of life. What is not known is the spirituality of children with a genetically inherited, life threatening disease, even though the literature is clear that there is a heightened spirituality in the adult and adolescent populations with similar diseases. This heightened spirituality has provided meaning to the adult and adolescents' life to promote healing. Healing does not mean cure in the usual use of the word, but instead a sense of health and well-being as experienced by hope, love, sense of control, relatedness with others, finding meaning and purpose in life and disease, and a sense that there is something greater than the self (Fryback, 1993; Mytko & Knight, 1999). The purpose of this study is to explore spirituality in children who are 8 -12 years of age and who have been diagnosed with the genetic, life-threatening disease of Duchenne Muscular Dystrophy. Giorgi's (1985) qualitative design will be used for this phenomenological study. Children 8 -12 years old with DMD will be recruited from a large, mid-western genetics clinic. Children will be invited to participate in the research until no new themes or meaning units are identified during the interviews. Interviews using open-ended questions and descriptions by the children of drawings they have made will elicit the data. Interview data will be transcribed to sheets of paper verbatim. Demographic information will be used to generate descriptive statistics for the sample population and to determine any religious belief systems that would help in the understanding of the child's responses to the questions. Analysis of the data will follow Giorgi's (1985) method of analysis. Rigor will be addressed through bracketing prior to interviewing and data analysis, using two different data collection strategies, development of a detailed Interview Schedule, using a peer debriefed, and developing an audit process for field notes and data analysis. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen
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Project Title: STRUCTURE/FUNCTION OF CH DOMAIN PROTEINS Principal Investigator & Institution: Matsudaira, Paul T. Professor of Biology and Bioengineering; Whitehead Institute for Biomedical Res Biomedical Research Cambridge, MA 02142 Timing: Fiscal Year 2001; Project Start 01-MAY-1998; Project End 30-JUN-2002 Summary: The Calponin-Homology (CH) domain identifies a new super family of cytoskeletal proteins that integrate the cytoskeleton and signalling pathways. Based on a small actin binding domain from calponin, the CH domain functions as a module that targets various proteins including signaling proteins, vav and IQGAP, and actin crosslinking proteins to actin filaments. More recently, CH domains were discovered in the IFAPs plectin and BPAB1n1 (dystonin) suggesting that they connect the actin and intermediate filament cytoskeletons. This widespread use of CH domains in important structural and signaling systems may provide a direct cellular mechanism for regulating cell structure. To understand how CH domain proteins organize the cytoskeleton, this proposal has three specific aims. The first goal is to describe the mechanism of cross
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linking by fibrin by determining the 3D structure of a fimbrin-actin cross link and by identifying interacting residues at the binding interface by site directed mutagenesis. This structure will serve as a model for understanding how CH domain proteins bind the actin cytoskeleton. The second aims to describe the function of the fibrin-vimentin complex at cell substratum adhesion sites. Interactions between the actin and IF cytoskeleton may play in important role in the assembly and/or stability of a cell attachment. The last aim is to identify the function of calponin by a combination of biochemical and genetic approaches. In the simple cytoskeleton of yeast which lacks the muscle contractile system, calponin should more closely represent its function in nonmuscle cells. The applicant points out that studies on CH domain proteins are directly relevant to understanding underlying mechanisms of disease. The oncogenic properties of vav, the onset of myotonic dystony, blood disorders, and muscular dystrophy are caused by defects in different members of the CH domain superfamily. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •
Project Title: STRUCTURE-FUNCTION ANALYSIS OF SARCOSPAN Principal Investigator & Institution: Crosbie, Rachelle H. Duchenne Musc Dyst Res Ctr; University of California Los Angeles 10920 Wilshire Blvd., Suite 1200 Los Angeles, CA 90024 Timing: Fiscal Year 2001; Project Start 24-SEP-2001; Project End 31-AUG-2006 Summary: (provided by applicant): The broad, long-term objectives of this proposal are to understand the structure and function of a novel tetraspanin called SARCOSPAN. Sarcospan is an integral component of the dystrophin-glycoprotein complex and is highly expressed in skeletal and cardiac muscles, as well as many non-muscle tissues (Crosbie et al., 1997; Crosbie et al., 1998; Crosbie et al., 1999). The dystrophinglycoprotein complex (DGC) is a structural complex that spans the muscle plasma membrane and links the extracellular matrix with the intracellular cytoskeleton. This structural linkage is critical for normal muscle function as clearly demonstrated by the many forms of muscular dystrophy that result from mutations in the dystrophinglycoprotein complex. Association of several signaling molecules with the DGC also suggests that this complex may play a role in mediating extracellular-intracellular communications. Furthermore, lateral associations amongst membrane components of the DGC are critical for function of this complex. It is hypothesized that sarcospan facilitates protein-protein interactions within the dystrophin-glycoprotein complex. These protein interactions are clearly important for the physical linkage between the extracellular matrix and the intracellular actin network and for the prevention of muscular dystrophy. Human mutations within the sarcospan gene have not been identified in known cases of autosomal recessive muscular dystrophy (Crosbie et al., 2000). However, these mutation searches have only examined the ubiquitous form of SSPN, which has a broad expression pattern. Preliminary data demonstrates that a novel, muscle-specific form of SSPN is expressed in skeletal and cardiac muscles. We hypothesize that mutations within muscle-SSPN may cause novel forms of muscular dystrophy. Identification and characterization of this muscle-sarcospan will advance our understanding of the role of the dystrophin-glycoprotein complex in normal muscle and in the pathogenesis of muscular dystrophy. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen
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Project Title: SURGICAL APPROACHES TO SYSTEMIC GENE TRANSFER Principal Investigator & Institution: Stedman, Hansell H. Assistant Professor; Surgery; University of Pennsylvania 3451 Walnut Street Philadelphia, PA 19104
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Timing: Fiscal Year 2002; Project Start 30-SEP-2002; Project End 31-AUG-2007 Summary: (provided by applicant): The overall aim of the proposed research is to improve the prospects for therapeutic gene transfer in Duchenne muscular dystrophy by addressing two essential rate-limiting issues: immunity to the transgene product and vector delivery. Using a newly described canine animal model for Duchenne muscular dystrophy, the German Short Haired Pointer, the experimental design takes advantage of a deletion of the dystrophin gene to evaluate the comparative immunogenicity of dystrophin and utrophin. We make exclusive use of rAAV vectors. The experimental design tests the hypothesis that in the context of the deletion, recombinant (canine) mini-dystrophin will elicit a deleterious cellular immune response. It further tests the hypothesis that substitution of a similarly designed canine mini-utrophin transgene will circumvent this immune response. Based on extensive preliminary data, the proposal also addresses the hypothesis that the endothelial barrier to systemic gene delivery can be bypassed by temporarily infusing histamine during a period of mechanical circulatory support. We propose a graded series of experiments to address the latter hypothesis, starting with isolated limb perfusion and culminating in systemic gene delivery. These studies will also make extensive use of another naturally occurring animal model, the hamster model for limb-girdle muscular dystrophy. Successful completion of the experimental plan will provide general information relevant to the immunological response to somatic gene delivery and the preservation of organ function during profound but rapidly reversible alterations in endothelial integrity. It will also provide specific information about the rational design of strategies for systemic gene therapy in one of the most common single-gene lethal diseases in man, Duchenne Muscular Dystrophy. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •
Project Title: SYMPATHETIC ACTIVITY AND OXYGENATION IN SKELETAL MUSCLE Principal Investigator & Institution: Victor, Ronald G. Associate Professor; University of Texas Sw Med Ctr/Dallas Dallas, TX 753909105 Timing: Fiscal Year 2001 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: TESTING MOLECULAR MODELS OF SPECTRIN FLEXIBILITY Principal Investigator & Institution: Macdonald, Ruby I. Biochem/Molecular & Cell Biol; Northwestern University 633 Clark St Evanston, IL 60208 Timing: Fiscal Year 2001; Project Start 01-JAN-1998; Project End 30-JUN-2005 Summary: (provided by applicant): The long-term objective of this proposal is to understand the molecular basis of flexibility of the ubiquitous cytoskeletal protein, spectrin, and its relatives, alpha-actinin and dystrophin. Continuing the previously successful strategy of determining the X-ray crystal structure of two connected repeating units of chicken brain alpha-spectrin, which led to the proposal of two of the first molecular models of spectrin flexibility, a follow-up investigation is proposed to critically test those models. The strengths of X-ray crystallography, fluorescence and nuclear magnetic resonance (NMR) spectroscopy will be exploited to address the following important questions about the models: 1) Is the conformation of a linker region coordinated with that of an adjacent linker region in a three repeat fragment? 2) Are linker regions predicted to be a random coil by secondary structure prediction
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methods nonhelical (which, if true, could suggest yet a third model of spectrin flexibility and also offer the possibility of studying mutations correlated with hereditary elliptocytosis)? 3) How does the absence of the nearly invariant tryptophan affect the conformation of the linker region and flexibility of two connected repeats? 4) Is conformational rearrangement of one of the previously determined structures-a key feature of one of the models--due to the phasing or to the sequence of the construct? To answer these crucial questions concerning models of spectrin flexibility, 3 structures will be determined by X-ray crystallography, 2 will be studied by fluorescence energy transfer and 10 will be analyzed by NMR. These three approaches will complement each other as the X-ray crystal structures will provide atomic distances for interpretation of energy transfer data and vector orientations for interpretation of NMR data, and energy transfer and NMR data will provide dynamic information about the crystal structures. The cloned spectrin fragments will also be characterized by their circular dichroism and fluorescence spectra, by their stabilities to urea and thermal denaturation and by their molecular weights on analytical ultracentrifugation. Proposed critical testing of molecular models of spectrin flexibility will contribute fundamental knowledge likely to advance understanding of conditions such as hereditary elliptocytosis and spherocytosis, muscular dystrophy, hydrops fetalis and Fanconi anemia, in all of which spectrin or spectrin-related proteins are abnormal or reduced in amount. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •
Project Title: THE NEW STEM CELL BIOLOGY Principal Investigator & Institution: Quesenberry, Peter J. Chief, Research Department; Roger Williams Hospital 825 Chalkstone Ave Providence, RI 02908 Timing: Fiscal Year 2003; Project Start 30-SEP-2003; Project End 30-JUN-2008 Summary: (provided by applicant): This COBRE grant has 4 major objectives: 1.) The development of a strong mentoring group of established investigators; 2.) The enhancement of infrastructure support through the development of core laboratories, administrative support, and resources; 3.) The recruitment and retention of young and established faculty at Roger Williams Medical Center (RWMC) and collaborating Providence institutions (Brown, Miriam Hospital, and Rhode Island Hospital) in order to continue the establishment of a major stem cell research center for the state, region, and country; and 4.) To define the capacity of marrow cells to produce skin and muscle cells, and to define the clinical potential of these approaches in murine wound healing and muscular dystrophy models, and to establish Vector Systems to use siRNA to inhibit stem cell transcriptional pathways and to assess the effect on the stem cell phenotype, beginning with PU.1. We have assembled an experienced group of scientists who will mentor 3 promising young investigators and are prepared to mentor others in different research areas. The work is thematically coordinated around stem cell biology and plasticity and transcriptional regulation of stem cells and the potential for using siRNA to redirect stem cell differentiation. The 3 projects and their P.I.s are: Project 1 Dr. Evangelos Badiavas - studies on the capacity of marrow cells to transdifferentiate (or convert) to skin cells and heal wounds. Project 2 - Dr. Mehrdad Abedi - the capacity of marrow cells to produce skeletal muscle cells and treat muscle disorders. Project 3 - Dr. Bharat Ramratnam - Stem cell gene modulation by RNAi. These scientific projects are supported by an Administrative Core, A Cell Sorter/Flow Cytometry Clore, and a Cell Phenotyping Core. Plans are outlined for continued mentoring of junior P.l.s, and specific approaches for evaluating the progress of the P.I.s. and a plan to specifically guide the P.l.s to RO1 funding is included. Institutional commitment is strong and not dependent on COBRE funding. Plans are also outlined for the recruitment and
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development of new junior faculty to the institutions and COBRE. The award of COBRE application would effectively facilitate the continued development of Center for Stem Cell Biology. This grant also has real promise in expanding understanding of stem cell plasticity and stem cell transcriptional regulation developing pre-clinical models for wound healing and muscular dystrophy.
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Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •
Project Title: THE ROLE OF DYSTROGLYCAN IN SIGNAL TRANSDUCTION Principal Investigator & Institution: Ruohola-Baker, T H. Associate Professor; Biochemistry; University of Washington Seattle, WA 98195 Timing: Fiscal Year 2003; Project Start 01-AUG-2003; Project End 30-JUN-2008 Summary: (provided by applicant): Dystroglycan (DG) is a key element of the dystrophin associated glycoprotein complex (DGC), which is closely linked to pathogenesis of several forms of muscular dystrophy. However, the basic cellular function of this DG complex is largely unknown. The overall objective of this project is to study the protein-protein interactions in which DG is involved in and their implications for cellular signaling. The extracellular matrix and cytoskeletal network are intricately interconnected, providing the cell with both structural integrity and a means for signal transduction. As a transmembrane protein, DG provides a physical link between the extra cellular matrix and cytoskeleton by attaching to laminin-2 at its Nterminus and to the cytoskeletal protein dystrophin at its C-terminus. Recent evidence has implicated DG in cellular signaling processes by binding to SH2/SH3 domain containing proteins, but the downstream signaling pathways are not clearly understood. To advance the understanding of DG's role in cellular signaling, this research aims to address the questions below in vitro and in vivo in Drosophila. 1) What is the biochemical basis of selective DG binding to Dystrophin, Grb2 and Src? 2) What is the functional significance of this selective binding? 3) What molecules, other than Dystrophin, Grb2 and Src interact with DG? We have recently isolated mutations in the DG gene and showed that DG is required for establishing the polarity in both the oocyte and the epithelial cell layers. By combining known biochemical data from mammalian systems with the advantages of Drosophila genetics and modern quantitative biochemistry we will dissect the functional role of differential protein binding by DG and identify new signaling molecules interacting with DG. In the future, we will investigate the developmental functions of DG associated signaling molecules. This research will advance the understanding of DG function in signal transduction and how it is regulated to mediate different intracellular pathways. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen
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Project Title: THE ROLE OF NUCLEAR LAMINS IN MUSCLE DISEASE Principal Investigator & Institution: Burke, Brian; Professor; Anatomy and Cell Biology; University of Florida Gainesville, FL 32611 Timing: Fiscal Year 2002; Project Start 01-JUL-2002; Project End 31-MAR-2007 Summary: (provided by applicant): A-type and B-type nuclear lamins form a family of nuclear envelope proteins that have an essential function in the maintenance of nuclear structure. Mutations in the human lamin A gene have been linked to several diseases which include Emery-Dreifuss muscular dystrophy (EDMD) and cardiomyopathy. Since the A-type lamins are found in majority of adult cell types it is extremely puzzling that defects in these proteins should be associated primarily with muscle specific disorders. The goal of this proposal is to elucidate the roles that individual lam in family
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members play in the organization of the cell nucleus and how in particular this relates to the maintenance of muscle integrity. The proposal will take advantage of mouse strains harboring targeted mutations in lamin genes, including a strain in which the lamin A gene has been deleted and which develops a disorder that closely resembles human EDMD. Inactivation of B-type lamin genes as well as the introduction of specific human disease-linked point mutations into the mouse lamin A gene will provide novel insight into the role of individual lamin proteins in nuclear organization and how this relates to disease processes in humans. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •
Project Title: THERAPEUTIC APPROACHES FOR MUSCULAR DYSTROPHY Principal Investigator & Institution: Spencer, Melissa J. Assistant Professor; Duchenne Musc Dyst Res Ctr; University of California Los Angeles 10920 Wilshire Blvd., Suite 1200 Los Angeles, CA 90024 Timing: Fiscal Year 2001; Project Start 05-MAY-2000; Project End 30-APR-2005 Summary: (appended verbatim from investigator's abstract): Duchenne muscular dystrophy (DMD) is the most common, inherited, lethal disease of childhood. Despite its high frequency of occurrence and the extensive knowledge of the molecular genetics of DMD, the lifespan or quality of life of DMD children has not improved over that which existed before the mutant gene was discovered approximately 13 years ago. Recently, our laboratories have shown that the histologically discernible pathology of the muscles of mdx mice, the most widely used animal model of the disease, could be reduced by more than half through interventions that inhibit cytotoxic T lymphocytes (CTLs). This is the greatest systemic improvement in the pathology of dystrophic muscle attained by any intervention, and it indicates that important new avenues for approaching DMD therapeutics may exist. The general goal of the investigation proposed here is to obtain more specific information concerning the role of T Iymphocytes in the death of dystrophic muscle, so that more specific therapeutic interventions with applicability to humans can be developed in future work. This will be done by: 1) determining whether distinct populations of T lymphocytes function through independent mechanisms in the autoreactive killing of mdx muscle, 2) testing whether binding of costimulatory molecules that are involved in Tcell activation is important for activation of autoreactive Tcells in mdx mice, and whether simultaneous blockade of these molecules is maximally effective for treatment, 3) testing whether the blockade of costimulating molecu1es of Tcells in mdx mice is most effective at reducing muscle pathology when applied early in the disease process, and 4) testing whether treatment of utrophin deficient mdx mice through Tcell depletions or with blockers of Tcell costimulation is effective in reducing muscle pathology and extending lifespan. Collectively, these findings can provide the basis for design of immune interventions to reduce the pathology of dystrophin deficient muscle. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen
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Project Title: DYSTROPHY
THERAPEUTIC
TRIAL
OF
PREDNISONE
IN
DUCHENE
Principal Investigator & Institution: Griggs, Robert C. Professor and Chair; University of Rochester Orpa - Rc Box 270140 Rochester, NY 14627 Timing: Fiscal Year 2001 Summary: To characterize the effect of corticosteroids on muscle protein metbolism in Duchenne dystrophy by studying whole body and muscle protein synthesis, muscle
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mass, and lean body mass. To determine if prednisone administration provokes changes in levels of hormones that might have a net anabolic effect on muscle. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •
Project Title: THIN FILAMENTS AND MUSCLE REGULATION Principal Investigator & Institution: Lehman, William J. Professor; Physiology and Biophysics; Boston University Medical Campus 715 Albany St, 560 Boston, MA 02118 Timing: Fiscal Year 2003; Project Start 30-SEP-1986; Project End 30-NOV-2007 Summary: (provided by applicant): Thin filament-associated actin-binding proteins control both actomyosin-based contractility and cytoskeletal formation in muscle and non-muscle cells. To elucidate these mechanisms, it is crucial to determine the structural interactions of the proteins involved. We address several interrelated questions fundamental to understanding muscle thin filament function: (1) What is the architecture of the thin filament in skeletal, cardiac and smooth muscles? (2) What are the changing structural interactions of thin filament-linked proteins that regulate muscle activity? (3) How do these proteins interact with actin to form the muscle cytoskeleton? We use state-of-the-art electron microscopy, image analysis and 3-D reconstruction to establish he macromolecular structure of components bound on thin filament actin. Using these techniques: (A) We aim to determine the structural basis of troponintropomyosin regulation of skeletal and cardiac muscle activity by analyzing interactions of tropomyosin and troponin on thin filaments and the effects of Ca2+ and myosincrossbridge binding. (B) To help understand the organization of the cortical actin cytoskeleton of muscle cells, we aim to determine the structural interactions of dystrophin and utrophin with filamentous F-actin by examining the binding of their distinct calponin homology (CH)-domains. (C) We aim to assess the structural role of thin filament associated caldesmon as a possible modulator of actomyosin-based motility and cytoskeletal assembly in smooth muscle. (D) Studies of the structure of nebulin bound to actin will be part of our continuing investigation of the functional design of thin filaments. In each study, reconstructions will be fitted to the atomic resolution maps of F-actin to define molecular contacts of binding proteins with actin. Further, such "hybrid crystallography" will be used to fit newly solved crystal structures of troponin, tropomyosin, dystrophin and utrophin domains within EM density maps to attain near atomic resolution. Our ongoing studies on troponin-trepomyosin regulated filaments will lead to an elucidation of the molecular mechanism of relaxation and activation in skeletal and cardiac muscle. Our successfully initiated structural studies on utrophin and dystrophin will establish their unique features as cytoskeletal elements, information applicable to designing genetic therapies for muscular dystrophy. Studies on smooth muscle filaments will contribute to understanding the fine-tuning of the smooth muscle contractile response. Such modulation affects vascular tone and pulmonary airway resistance, determinants in, e.g., hypertension and asthma. The wider significance of our goals is underscored by the role of actin and associated proteins in diverse and vital cellular mechanisms that can become aberrant in malignancy. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen
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Project Title: TRAINING PROGRAM IN THE NEUROSCIENCES Principal Investigator & Institution: Llinas, Rodolfo R. Chairman; Physiology and Neuroscience; New York University School of Medicine 550 1St Ave New York, NY 10016 Timing: Fiscal Year 2001; Project Start 01-JUL-2000; Project End 30-JUN-2005
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Summary: (ADAPTED FROM THE APPLICANT'S ABSTRACT): This application is for a new, broad based neuroscience program at the New York University School of Medicine. The training faculty includes 28 distinguished neuroscientists representing the Departments of Cell Biology, Neurology, Neurosurgery, Ophthalmology, Pharmacology, and Physiology & Neuroscience. The diverse research interests of the program faculty include molecular neurobiology, developmental genetics, synaptogenesis, neuron and glial cell structure and function, signal transduction, ion channel and receptor function, motor and sensory systems, brain imaging and cognition. This program will provide solid, broad based training of predoctoral students, with the overall goal to produce competitive, skillful neuroscientists positioned to make significant and diverse contributions to the field. Towards this goal, trainees will participate in a number of core and advanced courses, weekly seminars, journal clubs and tutorials that are designed to ensure broad exposure in the neurosciences. Research collaborations between trainees and participating faculty will be fostered through initial laboratory rotations followed by mentoring of dissertation studies by individual faculty members. The basic and clinical neuroscientists that make up the program faculty will emphasis training relevant to disorders of the nervous system such as Alzheimer's, multiple sclerosis, Parkinson's, muscular dystrophy, Tay-Sachs, stroke and spinal cord injury. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •
Project Title: TRANSLATIONAL RESEARCH IN THE DYSTROPHINOPATHIES Principal Investigator & Institution: Flanigan, Kevin M. Associate Professor; Neurology; University of Utah 200 S University St Salt Lake City, UT 84112 Timing: Fiscal Year 2002; Project Start 20-SEP-2002; Project End 31-JUL-2005 Summary: (provided by applicant): Duchenne Muscular Dystrophy (DMD) and Becker Muscular Dystrophy (BMD) are devastating disorders. Both are associated with mutations in the dystrophin gene, a huge gene with 79 exons spread over 2.4 million bases of genomic sequence. Deletions of large portions of the gene account for around 60% of all dystrophin mutations. The remainder consist of point mutations (primarily premature stop codon mutations), small deletions resulting in shift of the reading frame, and (in less than 5%) duplications. Dystrophin gene deletion testing is commercially and readily available, but point mutation testing is not. Recent studies in the mdx mouse, a model for DMD due to a premature stop codon mutation, have demonstrated the ability of aminoglycosides to increase the expression of dystrophin protein via induction of increased read-through. Recently, we and others have demonstrated some rules for the specificity of this effect, and a growing body of data suggests that aminoglycoside therapy may prove beneficial in some patients. We have developed the methodology to rapidly, robustly, and economically perform direct sequence analysis of the entire coding and regulatory regions of the dystrophin gene, greatly expediting the characterization of mutations in non-deleted dystrophinopathy patients. Using this methodology, we propose to characterize the mutations responsible for DMD and BMD in a large cohort of patients, from whom a standardized and thorough phenotypic characterization, will be obtained. Phenotype/genotype information will be compiled in a pilot dystrophinopathy registry database. Correlation of the phenotype to the sequence context of specific individual mutations will generate hypotheses of aminoglycoside-induced read-through efficiency in specific sequence contexts, which will be tested in an in vitro dual-luciferase transfection assay. This same assay will be used to systematically study other pharmaceutical compounds, which may cause readthrough of premature stop codon or frameshift mutations, and to study other potential
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mechanisms for modifying intrinsic frame shifting and read-through. Finally, we propose to develop a dual-GFP transgenic mouse, which will allow in vivo characterization of tissue-specific variation in aminoglycoside-induced read-through. Although we do not propose to perform an aminoglycoside treatment trial at present, this proposed study will identify a cohort of patients who may be candidates for any future trials here or at other institutions, and may provide a rationale to suggest that individual compounds or dosages may need to be tailored to specific sequence variations in all future trials. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •
Project Title: TRI-NUCLEOTIDE REPEAT AND FRAGILE SITES IN YEAST Principal Investigator & Institution: Zakian, Virginia A. Harry C. Weiss Professor in the Life Sci; Molecular Biology; Princeton University 4 New South Building Princeton, NJ 085440036 Timing: Fiscal Year 2001; Project Start 29-APR-1998; Project End 28-FEB-2003 Summary: (adapted from investigator's abstract): An ever-increasing number of human genetic diseases are attributed to expansion of trinucleotide repeats (TNRs). For example fragile X syndrome, the second leading cause of mental retardation, is due to expansion of a CGG tract and myotonic muscular dystrophy, is due to expansion of a CTG tract. Moreover, expansion of CGG tracts induce breakage at five known human chromosomal loci, some of which correlate with human disease. Chromosome breakage at fragile site is also implicated in the chromosomal rearrangements characteristic of human tumors. TNRs associated with human disease are rare. TNR and fragile site research would be greatly aided by genetic assays for tract expansion and/or chromosome fragility. The goal of this grant is to develop Saccharomyces cerevisiae as a model for TNR expansion and triplet-mediate chromosome fragility. The investigator has inserted 130 repeats of CTG onto a yeast chromosome. Large expansion of this tract were obtained, the first large expansion reported outside of humans. CTG tracts may also be length-dependent fragile sites in yeast. This observation provides the basis for a simple, genetic assay for tract expansion and chromosome fragility. The assays will be used to identify yeast and human genes whose mutation or over-expression increases CTG expansion and/or fragility. A premise of the proposed work is that most genes that affect TNR stability will encode proteins involved in replication, repair, or chromatin structure, many of which are conserved from yeast to humans. The behavior of CGG tracts will also be studied. Nucleases and DNA methylases will be used to analyze the chromatin structure of CTG and CGG tracts as both DNAs display unusual nucleosome forming properties in vitro. Finally, fragile sites are thought to be caused by late replication of TNR DNA. This model will be tested using density transfer and twodimensional gel electrophoresis to determine if replication timing or replication fork progression is affected by the presence of TNRs. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen
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Project Title: VENTRICULAR DYSFUNCTION/NEUROHUMORAL ACTIVATION-DMD Principal Investigator & Institution: Zimmerman, Frank; Washington University Lindell and Skinker Blvd St. Louis, MO 63130 Timing: Fiscal Year 2001 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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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 “muscular dystrophy” (or synonyms) into the search box. This search gives you access to full-text articles. The following is a sample of items found for muscular dystrophy in the PubMed Central database: •
A 71-Kilodalton Protein is a Major Product of the Duchenne Muscular Dystrophy Gene in Brain and Other Nonmuscle Tissues. by Lederfein D, Levy Z, Augier N, Mornet D, Morris G, Fuchs O, Yaffe D, Nudel U. 1992 Jun 15; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&rendertype=abstr act&artid=49288
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A second promoter provides an alternative target for therapeutic up-regulation of utrophin in Duchenne muscular dystrophy. by Burton EA, Tinsley JM, Holzfeind PJ, Rodrigues NR, Davies KE. 1999 Nov 23; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=24184
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Adeno-associated virus vector carrying human minidystrophin genes effectively ameliorates muscular dystrophy in mdx mouse model. by Wang B, Li J, Xiao X. 2000 Dec 5; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=17641
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Altered phosphorylation and intracellular distribution of a (CUG) n triplet repeat RNA-binding protein in patients with myotonic dystrophy and in myotonin protein kinase knockout mice. by Roberts R, Timchenko NA, Miller JW, Reddy S, Caskey CT, Swanson MS, Timchenko LT. 1997 Nov 25; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=24290
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Brain dystrophin-glycoprotein complex: Persistent expression of beta-dystroglycan, impaired oligomerization of Dp71 and up-regulation of utrophins in animal models of muscular dystrophy. by Culligan K, Glover L, Dowling P, Ohlendieck K. 2001; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=29067
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Detection of Dystrophin in the Postsynaptic Density of Rat Brain and Deficiency in a Mouse Model of Duchenne Muscular Dystrophy. by Kim T, Wu K, Xu J, Black IB. 1992 Dec 1; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&rendertype=abstr act&artid=50609
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Expansion of a CUG trinucleotide repeat in the 3[prime prime or minute] untranslated region of myotonic dystrophy protein kinase transcripts results in
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Adapted from the National Library of Medicine: http://www.pubmedcentral.nih.gov/about/intro.html.
With PubMed Central, NCBI is taking the lead in preservation and maintenance of open access to electronic literature, just as NLM has done for decades with printed biomedical literature. PubMed Central aims to become a world-class library of the digital age. 5 The value of PubMed Central, in addition to its role as an archive, lies in the availability of data from diverse sources stored in a common format in a single repository. Many journals already have online publishing operations, and there is a growing tendency to publish material online only, to the exclusion of print.
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nuclear retention of transcripts. by Davis BM, McCurrach ME, Taneja KL, Singer RH, Housman DE. 1997 Jul 8; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=23831 •
Fission yeast orb6, a ser /thr protein kinase related to mammalian rho kinase and myotonic dystrophy kinase, is required for maintenance of cell polarity and coordinates cell morphogenesis with the cell cycle. by Verde F, Wiley DJ, Nurse P. 1998 Jun 23; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=22672
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Functional muscle ischemia in neuronal nitric oxide synthase-deficient skeletal muscle of children with Duchenne muscular dystrophy. by Sander M, Chavoshan B, Harris SA, Iannaccone ST, Stull JT, Thomas GD, Victor RG. 2000 Dec 5; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=17659
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Identification of a (CUG)n triplet repeat RNA-binding protein and its expression in myotonic dystrophy. by Timchenko LT, Miller JW, Timchenko NA, DeVore DR, Datar KV, Lin L, Roberts R, Caskey CT, Swanson MS. 1996 Nov 15; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&rendertype=abstr act&artid=146274
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Intermolecular and Intramolecular Interactions Regulate Catalytic Activity of Myotonic Dystrophy Kinase-Related Cdc42-Binding Kinase [alpha]. by Tan I, Seow KT, Lim L, Leung T. 2001 Apr 15; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&rendertype=exter nal&artid=86907
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Long-term persistence of donor nuclei in a Duchenne muscular dystrophy patient receiving bone marrow transplantation. by Gussoni E, Bennett RR, Muskiewicz KR, Meyerrose T, Nolta JA, Gilgoff I, Stein J, Chan YM, Lidov HG, Bonnemann CG, von Moers A, Morris GE, den Dunnen JT, Chamberlain JS, Kunkel LM, Weinberg K. 2002 Sep 15; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=151133
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Molecular Basis for Impaired Muscle Differentiation in Myotonic Dystrophy. by Timchenko NA, Iakova P, Cai ZJ, Smith JR, Timchenko LT. 2001 Oct 15; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&rendertype=exter nal&artid=99869
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Myotonic Dystrophy Kinase-Related Cdc42-Binding Kinase Acts as a Cdc42 Effector in Promoting Cytoskeletal Reorganization. by Leung T, Chen XQ, Tan I, Manser E, Lim L. 1998 Jan; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&rendertype=exter nal&artid=121465
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Myotonic dystrophy: molecular windows on a complex etiology. by Korade-Mirnics Z, Babitzke P, Hoffman E. 1998 Mar 15; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&rendertype=abstr act&artid=147423
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Neuronal Nitric Oxide Synthase and Dystrophin-Deficient Muscular Dystrophy. by Chang W, Iannaccone ST, Lau KS, Masters BS, McCabe TJ, McMillan K, Padre RC, Spencer MJ, Tidball JG, Stull JT. 1996 Aug 20; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&rendertype=abstr act&artid=38609
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NO skeletal muscle derived relaxing factor in Duchenne muscular dystrophy. by Bredt DS. 1998 Dec 8; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=33925
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Overexpression of the cytotoxic T cell GalNAc transferase in skeletal muscle inhibits muscular dystrophy in mdx mice. by Nguyen HH, Jayasinha V, Xia B, Hoyte K, Martin PT. 2002 Apr 16; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=122819
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Possible Influences on the Expression of X Chromosome-Linked Dystrophin Abnormalities by Heterozogosity of Autosomal Recessive Fukuyama Congenital Muscular Dystrophy. by Beggs AH, Neumann PE, Arahata K, Arikawa E, Nonaka I, Anderson MS, Kunkel LM. 1992 Jan 15; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&rendertype=abstr act&artid=48291
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Profound misregulation of muscle-specific gene expression in facioscapulohumeral muscular dystrophy. by Tupler R, Perini G, Pellegrino MA, Green MR. 1999 Oct 26; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=23032
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Social deprivation in Duchenne muscular dystrophy: population based study. by Bushby K, Raybould S, O'Donnell S, Steele JG. 2001 Nov 3; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=59456
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Structural analysis of slipped-strand DNA (S-DNA) formed in (CTG)n. (CAG)n repeats from the myotonic dystrophy locus. by Pearson CE, Wang YH, Griffith JD, Sinden RR. 1998 Feb 1; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&rendertype=abstr act&artid=147324
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Structure and dynamics of the DNA hairpins formed by tandemly repeated CTG triplets associated with myotonic dystrophy. by Mariappan SV, Garcoa AE, Gupta G. 1996 Feb 15; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&rendertype=abstr act&artid=145682
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The role of basal and myogenic factors in the transcriptional activation of utrophin promoter A: implications for therapeutic up-regulation in Duchenne muscular dystrophy. by Perkins KJ, Burton EA, Davies KE. 2001 Dec 1; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&rendertype=exter nal&artid=96689
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Transcriptional abnormality in myotonic dystrophy affects DMPK but not neighboring genes. by Hamshere MG, Newman EE, Alwazzan M, Athwal BS, Brook JD. 1997 Jul 8; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=23832
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Transgenic overexpression of caveolin-3 in skeletal muscle fibers induces a Duchenne-like muscular dystrophy phenotype. by Galbiati F, Volonte D, Chu JB, Li M, Fine SW, Fu M, Bermudez J, Pedemonte M, Weidenheim KM, Pestell RG, Minetti C, Lisanti MP. 2000 Aug 15; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=16926
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Triple Repeat Expansion in Myotonic Dystrophy Alters the Adjacent Chromatin Structure. by Otten AD, Tapscott SJ. 1995 Jun 6; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&rendertype=abstr act&artid=41715
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Ullrich scleroatonic muscular dystrophy is caused by recessive mutations in collagen type VI. by Camacho Vanegas O, Bertini E, Zhang RZ, Petrini S, Minosse C, Sabatelli P, Giusti B, Chu ML, Pepe G. 2001 Jun 19; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=34700
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 muscular dystrophy, simply go to the PubMed Web site at http://www.ncbi.nlm.nih.gov/pubmed. Type “muscular dystrophy” (or synonyms) into the search box, and click “Go.” The following is the type of output you can expect from PubMed for muscular dystrophy (hyperlinks lead to article summaries): •
A case of Bartter's syndrome, gout and Becker's muscular dystrophy. Author(s): Fishel B, Zhukovsky G, Legum C, Jossiphov J, Alon M, Peer G, Iaina A, Nevo Y. Source: Clin Exp Rheumatol. 2000 May-June; 18(3): 426-7. No Abstract Available. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10895394&dopt=Abstract
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A case of limb-girdle muscular dystrophy with serum anti-nuclear antibody which led to a mistaken diagnosis of polymyositis. Author(s): Funauchi M, Nozaki Y, Yoo BS, Kinoshita K, Kanamaru A. Source: Clin Exp Rheumatol. 2002 September-October; 20(5): 707-8. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12412206&dopt=Abstract
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A case of merosin-negative congenital muscular dystrophy with extensive white matter abnormalities and electroencephalographic changes in a Syrian boy. Author(s): Al-Ajmi MO, Abdulla JK, Neubauer D. Source: J Med Liban. 2001 May-June; 49(3): 173-8. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12184464&dopt=Abstract
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PubMed was developed by the National Center for Biotechnology Information (NCBI) at the National Library of Medicine (NLM) at the National Institutes of Health (NIH). The PubMed database was developed in conjunction with publishers of biomedical literature as a search tool for accessing literature citations and linking to full-text journal articles at Web sites of participating publishers. Publishers that participate in PubMed supply NLM with their citations electronically prior to or at the time of publication.
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A case of oculopharyngeal muscular dystrophy in a Bulgarian Jew. Author(s): Schwartz J, Rosenfeld V. Source: Journal of the American Geriatrics Society. 1993 October; 41(10): 1156-7. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=8409167&dopt=Abstract
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A comparative gene expression analysis of Emery-Dreifuss muscular dystrophy using a cDNA microarray. Author(s): Tsukahara T, Arahata K. Source: Methods in Molecular Biology (Clifton, N.J.). 2003; 217: 253-62. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12491938&dopt=Abstract
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A comparison of the stress and coping strategies between the parents of children with Duchenne muscular dystrophy and children with a fever. Author(s): Chen JY, Chen SS, Jong YJ, Yang YH, Chang YY. Source: Journal of Pediatric Nursing. 2002 October; 17(5): 369-79. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12395305&dopt=Abstract
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A dystrophin-associated glycoprotein, A3a (one of 43DAG doublets), is retained in Duchenne muscular dystrophy muscle. Author(s): Yoshida M, Mizuno Y, Nonaka I, Ozawa E. Source: Journal of Biochemistry. 1993 November; 114(5): 634-9. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=8113213&dopt=Abstract
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A missense mutation in the exon 8 of lamin A/C gene in a Japanese case of autosomal dominant limb-girdle muscular dystrophy and cardiac conduction block. Author(s): Kitaguchi T, Matsubara S, Sato M, Miyamoto K, Hirai S, Schwartz K, Bonne G. Source: Neuromuscular Disorders : Nmd. 2001 September; 11(6-7): 542-6. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11525883&dopt=Abstract
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A multicenter, double-blind, randomized trial of deflazacort versus prednisone in Duchenne muscular dystrophy. Author(s): Bonifati MD, Ruzza G, Bonometto P, Berardinelli A, Gorni K, Orcesi S, Lanzi G, Angelini C. Source: Muscle & Nerve. 2000 September; 23(9): 1344-7. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10951436&dopt=Abstract
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A mutation in the X-linked Emery-Dreifuss muscular dystrophy gene in a patient affected with conduction cardiomyopathy. Author(s): Vohanka S, Vytopil M, Bednarik J, Lukas Z, Kadanka Z, Schildberger J, Ricotti R, Bione S, Toniolo D. Source: Neuromuscular Disorders : Nmd. 2001 May; 11(4): 411-3. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11369194&dopt=Abstract
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A new approach to the therapy of Duchenne muscular dystrophy with early precursors of myogenesis. Author(s): Sukhikh GT, Malaitsev VV, Bogdanova IM, Dubrovina IV, Sitnikov VF. Source: Bulletin of Experimental Biology and Medicine. 2001 December; 132(6): 1131-8. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12152867&dopt=Abstract
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A new dysferlin gene mutation in two Japanese families with limb-girdle muscular dystrophy 2B and Miyoshi myopathy. Author(s): Ueyama H, Kumamoto T, Nagao S, Masuda T, Horinouchi H, Fujimoto S, Tsuda T. Source: Neuromuscular Disorders : Nmd. 2001 March; 11(2): 139-45. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11257469&dopt=Abstract
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A new form of muscular dystrophy with mitochondrial structural abnormalities. Author(s): Ikemoto-Tsuchiya K, Nishino I, Kawai M, Morimatsu M, Nonaka I. Source: Muscle & Nerve. 2001 December; 24(12): 1710-1. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11745984&dopt=Abstract
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A new locus for autosomal recessive limb-girdle muscular dystrophy in a large consanguineous Tunisian family maps to chromosome 19q13.3. Author(s): Driss A, Amouri R, Ben Hamida C, Souilem S, Gouider-Khouja N, Ben Hamida M, Hentati F. Source: Neuromuscular Disorders : Nmd. 2000 June; 10(4-5): 240-6. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10838249&dopt=Abstract
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A nitric oxide synthase transgene ameliorates muscular dystrophy in mdx mice. Author(s): Wehling M, Spencer MJ, Tidball JG. Source: The Journal of Cell Biology. 2001 October 1; 155(1): 123-31. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11581289&dopt=Abstract
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A noninvasive means of detecting preclinical cardiomyopathy in Duchenne muscular dystrophy? Author(s): Towbin JA. Source: Journal of the American College of Cardiology. 2003 July 16; 42(2): 317-8. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12875770&dopt=Abstract
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A novel insert mutation in gamma-sarcoglycan gene leads to severe childhood autosomal recessive muscular dystrophy. Author(s): Lin S, Ramelli GP, Moser H, Gallati S, Burgunder JM. Source: Journal of Neurology. 2002 November; 249(11): 1608-11. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12532930&dopt=Abstract
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A novel laminin alpha2 isoform in severe laminin alpha2 deficient congenital muscular dystrophy. Author(s): Pegoraro E, Fanin M, Trevisan CP, Angelini C, Hoffman EP. Source: Neurology. 2000 October 24; 55(8): 1128-34. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11071490&dopt=Abstract
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A novel, blood-based diagnostic assay for limb girdle muscular dystrophy 2B and Miyoshi myopathy. Author(s): Ho M, Gallardo E, McKenna-Yasek D, De Luna N, Illa I, Brown Jr RH. Source: Annals of Neurology. 2002 January; 51(1): 129-33. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11782994&dopt=Abstract
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A protein truncation test for Emery-Dreifuss muscular dystrophy (EMD): detection of N-terminal truncating mutations. Author(s): de Koning Gans PA, Ginjaar I, Bakker E, Yates JR, den Dunnen JT. Source: Neuromuscular Disorders : Nmd. 1999 June; 9(4): 247-50. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10399752&dopt=Abstract
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A randomized comparative study of two methods for controlling Tendo Achilles contracture in Duchenne muscular dystrophy. Author(s): Hyde SA, FlLytrup I, Glent S, Kroksmark AK, Salling B, Steffensen BF, Werlauff U, Erlandsen M. Source: Neuromuscular Disorders : Nmd. 2000 June; 10(4-5): 257-63. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10838252&dopt=Abstract
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A sensitive assay of tumor necrosis factor alpha in sera from Duchenne muscular dystrophy patients. Author(s): Saito K, Kobayashi D, Komatsu M, Yajima T, Yagihashi A, Ishikawa Y, Minami R, Watanabe N. Source: Clinical Chemistry. 2000 October; 46(10): 1703-4. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11017956&dopt=Abstract
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A standardized method for the evaluation of respiratory muscle endurance in patients with Duchenne muscular dystrophy. Author(s): Matecki S, Topin N, Hayot M, Rivier F, Echenne B, Prefaut C, Ramonatxo M. Source: Neuromuscular Disorders : Nmd. 2001 March; 11(2): 171-7. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11257474&dopt=Abstract
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A variant of congenital muscular dystrophy. Author(s): Yoshioka M, Kuroki S, Sasaki H, Baba K, Toda T. Source: Brain & Development. 2002 January; 24(1): 24-9. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11751021&dopt=Abstract
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Aberrant neuronal migration in the brainstem of fukuyama-type congenital muscular dystrophy. Author(s): Saito Y, Kobayashi M, Itoh M, Saito K, Mizuguchi M, Sasaki H, Arima K, Yamamoto T, Takashima S, Sasaki M, Hayashi K, Osawa M. Source: Journal of Neuropathology and Experimental Neurology. 2003 May; 62(5): 497508. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12769189&dopt=Abstract
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Abnormal signal-averaged electrocardiogram in patients with Duchenne muscular dystrophy: comparison of time and frequency domain analyses from the signalaveraged electrocardiogram. Author(s): Kubo M, Matsuoka S, Hayabuchi Y, Akita H, Matsuka Y, Kuroda Y. Source: Clin Cardiol. 1993 October; 16(10): 723-8. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=8222385&dopt=Abstract
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Abnormality of the myocardial sympathetic nervous system in a patient with Becker muscular dystrophy detected with iodine-123 metaiodobenzylguanidine scintigraphy. Author(s): Kaminaga T, Matsumura K, Hatanaka H, Shimizu T. Source: Clinical Nuclear Medicine. 2001 August; 26(8): 701-3. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11452178&dopt=Abstract
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Absence of hearing impairment in adult onset facioscapulohumeral muscular dystrophy. Author(s): Rogers MT, Zhao F, Harper PS, Stephens D. Source: Neuromuscular Disorders : Nmd. 2002 May; 12(4): 358-65. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12062253&dopt=Abstract
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Activities of daily living and quality of life in persons with muscular dystrophy. Author(s): Natterlund B, Ahlstrom G. Source: Journal of Rehabilitation Medicine : Official Journal of the Uems European Board of Physical and Rehabilitation Medicine. 2001 September; 33(5): 206-11. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11585151&dopt=Abstract
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Acute heart failure during spinal surgery in a boy with Duchenne muscular dystrophy. Author(s): Schmidt GN, Burmeister MA, Lilje C, Wappler F, Bischoff P. Source: British Journal of Anaesthesia. 2003 June; 90(6): 800-4. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12765898&dopt=Abstract
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Adeno-associated virus vector carrying human minidystrophin genes effectively ameliorates muscular dystrophy in mdx mouse model. Author(s): Wang B, Li J, Xiao X. Source: Proceedings of the National Academy of Sciences of the United States of America. 2000 December 5; 97(25): 13714-9. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11095710&dopt=Abstract
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Adequate tidal volume with row-a-boat phenomenon in advanced Duchenne muscular dystrophy. Author(s): Yasuma F, Kato T, Naya M. Source: Chest. 2002 May; 121(5): 1726. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12006480&dopt=Abstract
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Adhalin deficiency: an unusual cause of muscular dystrophy. Author(s): Dua T, Kalra V, Sharma MC, Kabra M. Source: Indian J Pediatr. 2001 November; 68(11): 1083-5. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11770249&dopt=Abstract
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Affection of mimic muscles, simulating damage of the facial nerve in patients with facioscapulohumeral muscular dystrophy. Author(s): Kazakov VM. Source: European Archives of Oto-Rhino-Laryngology : Official Journal of the European Federation of Oto-Rhino-Laryngological Societies (Eufos) : Affiliated with the German Society for Oto-Rhino-Laryngology - Head and Neck Surgery. 1994 December; : S96-101. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10774323&dopt=Abstract
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Age and origin of the FCMD 3'-untranslated-region retrotransposal insertion mutation causing Fukuyama-type congenital muscular dystrophy in the Japanese population. Author(s): Colombo R, Bignamini AA, Carobene A, Sasaki J, Tachikawa M, Kobayashi K, Toda T. Source: Human Genetics. 2000 December; 107(6): 559-67. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11153909&dopt=Abstract
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Airway nitric oxide in Duchenne muscular dystrophy. Author(s): Straub V, Ratjen F, Amthor H, Voit T, Grasemann H. Source: The Journal of Pediatrics. 2002 July; 141(1): 132-4. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12091865&dopt=Abstract
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Alpha-sarcoglycanopathy previously misdiagnosed as Duchenne muscular dystrophy: implications for current diagnostics and patient care. Author(s): Schara U, Gencik M, Mortier J, Langen M, Gencikova A, Epplen JT, Mortier W. Source: European Journal of Pediatrics. 2001 July; 160(7): 452-3. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11475588&dopt=Abstract
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Alterations of the retino-cortical conduction in patients affected by classical congenital muscular dystrophy (CI-CMD) with merosin deficiency. Author(s): Tormene AP, Trevisan C, Martinello F, Riva C, Pastorello E. Source: Documenta Ophthalmologica. Advances in Ophthalmology. 1999; 98(2): 127-38. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10946999&dopt=Abstract
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Altered regional brain glucose metabolism in Duchenne muscular dystrophy: a pet study. Author(s): Lee JS, Pfund Z, Juhasz C, Behen ME, Muzik O, Chugani DC, Nigro MA, Chugani HT. Source: Muscle & Nerve. 2002 October; 26(4): 506-12. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12362416&dopt=Abstract
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Aminoglycoside treatment for muscular dystrophy is scientifically rational, but is it clinically effective? Author(s): Hirano M. Source: Curr Neurol Neurosci Rep. 2002 January; 2(1): 53-4. No Abstract Available. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11898583&dopt=Abstract
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An attempt of gene therapy in Duchenne muscular dystrophy: overexpression of utrophin in transgenic mdx mice. Author(s): Gillis JM. Source: Acta Neurol Belg. 2000 September; 100(3): 146-50. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11098286&dopt=Abstract
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An autosomal dominant early adult-onset distal muscular dystrophy. Author(s): Zimprich F, Djamshidian A, Hainfellner JA, Budka H, Zeitlhofer J. Source: Muscle & Nerve. 2000 December; 23(12): 1876-9. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11102913&dopt=Abstract
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An early onset muscular dystrophy with diaphragmatic involvement, early respiratory failure and secondary alpha2 laminin deficiency unlinked to the LAMA2 locus on 6q22. Author(s): Muntoni F, Taylor J, Sewry CA, Naom I, Dubowitz V. Source: European Journal of Paediatric Neurology : Ejpn : Official Journal of the European Paediatric Neurology Society. 1998; 2(1): 19-26. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10726842&dopt=Abstract
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An inherited 4q35-EcoRI-DNA-fragment of 35 kb in a family with a sporadic case of facioscapulohumeral muscular dystrophy (FSHD). Author(s): Busse K, Kohler J, Stegmann K, Pongratz D, Koch MC, Schreiber H. Source: Neuromuscular Disorders : Nmd. 2000 March; 10(3): 178-81. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10734264&dopt=Abstract
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An STS map of the limb girdle muscular dystrophy type 2A region. Author(s): Richard I, Roudaut C, Fougerousse F, Chiannilkulchai N, Beckmann JS. Source: Mammalian Genome : Official Journal of the International Mammalian Genome Society. 1995 October; 6(10): 754-6. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=8563179&dopt=Abstract
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Anaesthetic management of a patient with Emery-Dreifuss muscular dystrophy. Author(s): Shende D, Agarwal R. Source: Anaesthesia and Intensive Care. 2002 June; 30(3): 372-5. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12075650&dopt=Abstract
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Analysis of dinucleotide repeat loci of dystrophin gene for carrier detection, germline mosaicism and de novo mutations in Duchenne muscular dystrophy. Author(s): Chaturvedi LS, Mittal RD, Srivastava S, Mukherjee M, Mittal B. Source: Clinical Genetics. 2000 September; 58(3): 234-6. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11076047&dopt=Abstract
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Analysis of dystrophin mRNA from skeletal muscle but not from lymphocytes led to identification of a novel nonsense mutation in a carrier of Duchenne muscular dystrophy. Author(s): Ito T, Takeshima Y, Yagi M, Kamei S, Wada H, Nakamura H, Matsuo M. Source: Journal of Neurology. 2003 May; 250(5): 581-7. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12736738&dopt=Abstract
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Andre Barbeau and the oculopharyngeal muscular dystrophy in French Canada and North America. Author(s): Bouchard JP. Source: Neuromuscular Disorders : Nmd. 1997 October; 7 Suppl 1: S5-11. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=9392008&dopt=Abstract
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Animal models for muscular dystrophy show different patterns of sarcolemmal disruption. Author(s): Straub V, Rafael JA, Chamberlain JS, Campbell KP. Source: The Journal of Cell Biology. 1997 October 20; 139(2): 375-85. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=9334342&dopt=Abstract
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Animal models for muscular dystrophy: valuable tools for the development of therapies. Author(s): Allamand V, Campbell KP. Source: Human Molecular Genetics. 2000 October; 9(16): 2459-67. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11005802&dopt=Abstract
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Apnoea in Duchenne muscular dystrophy. Author(s): Barbe F, Quera-Salva MA, Agusti AG. Source: Thorax. 1995 October; 50(10): 1123. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=7491569&dopt=Abstract
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Assessment of cardiac function in adolescents with Duchenne muscular dystrophy: importance of neurohormones. Author(s): Ramaciotti C, Scott WA, Lemler MS, Haverland C, Iannaccone ST. Source: Journal of Child Neurology. 2002 March; 17(3): 191-4. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12026234&dopt=Abstract
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Assessment of left ventricular systolic and diastolic functions in children with merosin-positive congenital muscular dystrophy. Author(s): Ceviz N, Alehan F, Alehan D, Ozme S, Akcoren Z, Kale G, Topaloglu H. Source: International Journal of Cardiology. 2003 February; 87(2-3): 129-33; Discussion 133-4. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12559529&dopt=Abstract
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Assignment of a form of congenital muscular dystrophy with secondary merosin deficiency to chromosome 1q42. Author(s): Brockington M, Sewry CA, Herrmann R, Naom I, Dearlove A, Rhodes M, Topaloglu H, Dubowitz V, Voit T, Muntoni F. Source: American Journal of Human Genetics. 2000 February; 66(2): 428-35. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10677302&dopt=Abstract
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Asymptomatic Becker muscular dystrophy: histological changes in biopsied muscles. Author(s): Tachi N, Watanabe Y, Ohya K, Chiba S. Source: Acta Paediatr Jpn. 1993 October; 35(5): 409-11. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=8256625&dopt=Abstract
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Ataxia and congenital muscular dystrophy: the follow-up of a new specific phenotype. Author(s): Trevisan CP, Pastorello E, Tonello S, Armani M, Rigoni MT, Tormene AP, Freda MP, Zortea M, Lombardi S. Source: Brain & Development. 2001 March; 23(2): 108-14. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11248459&dopt=Abstract
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Augmented synthesis and differential localization of heparan sulfate proteoglycans in Duchenne muscular dystrophy. Author(s): Alvarez K, Fadic R, Brandan E. Source: Journal of Cellular Biochemistry. 2002; 85(4): 703-13. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11968010&dopt=Abstract
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Autosomal dominant Emery-Dreifuss muscular dystrophy: a new family with late diagnosis. Author(s): Colomer J, Iturriaga C, Bonne G, Schwartz K, Manilal S, Morris GE, Puche M, Fernandez-Alvarez E. Source: Neuromuscular Disorders : Nmd. 2002 January; 12(1): 19-25. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11731280&dopt=Abstract
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Autosomal dominant limb-girdle muscular dystrophy: a large kindred with evidence for anticipation. Author(s): Gamez J, Navarro C, Andreu AL, Fernandez JM, Palenzuela L, Tejeira S, Fernandez-Hojas R, Schwartz S, Karadimas C, DiMauro S, Hirano M, Cervera C. Source: Neurology. 2001 February 27; 56(4): 450-4. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11222786&dopt=Abstract
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Basement membrane abnormality in merosin-negative congenital muscular dystrophy. Author(s): Osari S, Kobayashi O, Yamashita Y, Matsuishi T, Goto M, Tanabe Y, Migita T, Nonaka I. Source: Acta Neuropathologica. 1996; 91(4): 332-6. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=8928608&dopt=Abstract
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Basic fibroblast growth factor and muscular dystrophy. Author(s): Lefaucheur JP, Sebille A. Source: Annals of Neurology. 1994 November; 36(5): 800. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=7979228&dopt=Abstract
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Basic fibroblast growth factor promotes in vivo muscle regeneration in murine muscular dystrophy. Author(s): Lefaucheur JP, Sebille A. Source: Neuroscience Letters. 1995 December 29; 202(1-2): 121-4. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=8787846&dopt=Abstract
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Becker muscular dystrophy associated with focal myositis on bone scintigraphy. Author(s): Minshew PT, Silverman ED, Samuels-Botts C. Source: Clinical Nuclear Medicine. 2000 December; 25(12): 1010-2. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11129135&dopt=Abstract
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Becker muscular dystrophy combined with X-linked Charcot-Marie-Tooth neuropathy. Author(s): Bergmann C, Senderek J, Hermanns B, Jauch A, Janssen B, Schroder JM, Karch D. Source: Muscle & Nerve. 2000 May; 23(5): 818-23. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10797409&dopt=Abstract
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Becker muscular dystrophy presenting as eosinophilic inflammatory myopathy in an infant. Author(s): Weinstock A, Green C, Cohen BH, Prayson RA. Source: Journal of Child Neurology. 1997 February; 12(2): 146-7. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=9075026&dopt=Abstract
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Becker muscular dystrophy presenting with complete heart block in the sixth decade. Author(s): Quinlivan R, Ball J, Dunckley M, Thomas DJ, Flinter F, Morgan-Hughes J. Source: Journal of Neurology. 1995 June; 242(6): 398-400. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=7561969&dopt=Abstract
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Becker muscular dystrophy with bundle branch reentry ventricular tachycardia. Author(s): Negri SM, Cowan MD. Source: Journal of Cardiovascular Electrophysiology. 1998 June; 9(6): 652-4. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=9654233&dopt=Abstract
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Becker muscular dystrophy with onset after 60 years. Author(s): Heald A, Anderson LV, Bushby KM, Shaw PJ. Source: Neurology. 1994 December; 44(12): 2388-90. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=7991131&dopt=Abstract
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Becker muscular dystrophy: an unusual presentation. Author(s): Bush A, Dubowitz V. Source: Archives of Disease in Childhood. 1994 January; 70(1): 71. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=8110014&dopt=Abstract
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Becker muscular dystrophy-related cardiomyopathy: a favorable response to medical therapy. Author(s): Doing AH, Renlund DG, Smith RA. Source: The Journal of Heart and Lung Transplantation : the Official Publication of the International Society for Heart Transplantation. 2002 April; 21(4): 496-8. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11927228&dopt=Abstract
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Becker-like muscular dystrophy in sisters. Author(s): Dioszeghy P, Molnar M, Mechler F. Source: European Archives of Psychiatry and Clinical Neuroscience. 1995; 245(6): 326-30. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=8527470&dopt=Abstract
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Becker's muscular dystrophy: a case report. Author(s): Seid D. Source: Ethiop Med J. 1997 January; 35(1): 63-5. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=9293149&dopt=Abstract
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Becker-type muscular dystrophy associated with hypertrophic cardiomyopathy. Author(s): Hayashi Y, Ikeda U, Ogawa T, Miyashita H, Sekiguchi H, Arahata K, Shimada K. Source: American Heart Journal. 1994 December; 128(6 Pt 1): 1264-6. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=7985617&dopt=Abstract
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Beta-sarcoglycan (A3b) mutations cause autosomal recessive muscular dystrophy with loss of the sarcoglycan complex. Author(s): Bonnemann CG, Modi R, Noguchi S, Mizuno Y, Yoshida M, Gussoni E, McNally EM, Duggan DJ, Angelini C, Hoffman EP. Source: Nature Genetics. 1995 November; 11(3): 266-73. Erratum In: Nat Genet 1996 January; 12(1): 110. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=7581449&dopt=Abstract
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Beta-sarcoglycan: characterization and role in limb-girdle muscular dystrophy linked to 4q12. Author(s): Lim LE, Duclos F, Broux O, Bourg N, Sunada Y, Allamand V, Meyer J, Richard I, Moomaw C, Slaughter C, et al. Source: Nature Genetics. 1995 November; 11(3): 257-65. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=7581448&dopt=Abstract
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Bethlem myopathy (BETHLEM) and Ullrich scleroatonic muscular dystrophy: 100th ENMC international workshop, 23-24 November 2001, Naarden, The Netherlands. Author(s): Pepe G, Bertini E, Bonaldo P, Bushby K, Giusti B, de Visser M, Guicheney P, Lattanzi G, Merlini L, Muntoni F, Nishino I, Nonaka I, Yaou RB, Sabatelli P, Sewry C, Topaloglu H, van der Kooi A. Source: Neuromuscular Disorders : Nmd. 2002 December; 12(10): 984-93. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12467756&dopt=Abstract
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Bethlem myopathy is not allelic to limb-girdle muscular dystrophy type 1A. Author(s): Speer MC, Yamaoka LH, Stajich J, Lewis K, Pericak-Vance MA, Stacy R, Tandan R, Fries TJ. Source: American Journal of Medical Genetics. 1995 August 28; 58(2): 197-8. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=8533815&dopt=Abstract
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Bethlem myopathy: a slowly progressive congenital muscular dystrophy with contractures. Author(s): Jobsis GJ, Boers JM, Barth PG, de Visser M. Source: Brain; a Journal of Neurology. 1999 April; 122 ( Pt 4): 649-55. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10219778&dopt=Abstract
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Bladder dysfunction in Duchenne muscular dystrophy. Author(s): MacLeod M, Kelly R, Robb SA, Borzyskowski M. Source: Archives of Disease in Childhood. 2003 April; 88(4): 347-9. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12651768&dopt=Abstract
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Blood loss in Duchenne muscular dystrophy: vascular smooth muscle dysfunction? Author(s): Noordeen MH, Haddad FS, Muntoni F, Gobbi P, Hollyer JS, Bentley G. Source: Journal of Pediatric Orthopaedics. Part B / European Paediatric Orthopaedic Society, Pediatric Orthopaedic Society of North America. 1999 July; 8(3): 212-5. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10399127&dopt=Abstract
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Body composition and energy expenditure in Duchenne muscular dystrophy. Author(s): Zanardi MC, Tagliabue A, Orcesi S, Berardinelli A, Uggetti C, Pichiecchio A. Source: European Journal of Clinical Nutrition. 2003 February; 57(2): 273-8. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12571659&dopt=Abstract
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Body composition determined with MR in patients with Duchenne muscular dystrophy, spinal muscular atrophy, and normal subjects. Author(s): Leroy-Willig A, Willig TN, Henry-Feugeas MC, Frouin V, Marinier E, Boulier A, Barzic F, Schouman-Claeys E, Syrota A. Source: Magnetic Resonance Imaging. 1997; 15(7): 737-44. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=9309604&dopt=Abstract
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Bone mineral density and fractures in boys with Duchenne muscular dystrophy. Author(s): Larson CM, Henderson RC. Source: Journal of Pediatric Orthopedics. 2000 January-February; 20(1): 71-4. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10641693&dopt=Abstract
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Botulinum toxin for amelioration of knee contracture in Duchenne muscular dystrophy. Author(s): von Wendt LO, Autti-Ramo IS. Source: European Journal of Paediatric Neurology : Ejpn : Official Journal of the European Paediatric Neurology Society. 1999; 3(4): 175-6. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10476367&dopt=Abstract
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Brain abnormalities in Duchenne muscular dystrophy: phosphorus-31 magnetic resonance spectroscopy and neuropsychological study. Author(s): Tracey I, Scott RB, Thompson CH, Dunn JF, Barnes PR, Styles P, Kemp GJ, Rae CD, Pike M, Radda GK. Source: Lancet. 1995 May 20; 345(8960): 1260-4. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=7746055&dopt=Abstract
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Brain alterations in the classical form of congenital muscular dystrophy. Clinical and neuroimaging follow-up of 12 cases and correlation with the expression of merosin in muscle. Author(s): Trevisan CP, Martinello F, Ferruzza E, Fanin M, Chevallay M, Tome FM. Source: Child's Nervous System : Chns : Official Journal of the International Society for Pediatric Neurosurgery. 1996 October; 12(10): 604-10. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=8934020&dopt=Abstract
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Brain biochemistry in Duchenne muscular dystrophy: a 1H magnetic resonance and neuropsychological study. Author(s): Rae C, Scott RB, Thompson CH, Dixon RM, Dumughn I, Kemp GJ, Male A, Pike M, Styles P, Radda GK. Source: Journal of the Neurological Sciences. 1998 October 8; 160(2): 148-57. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=9849797&dopt=Abstract
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Brain function in Duchenne muscular dystrophy. Author(s): Anderson JL, Head SI, Rae C, Morley JW. Source: Brain; a Journal of Neurology. 2002 January; 125(Pt 1): 4-13. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11834588&dopt=Abstract
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Brain magnetic resonance imaging abnormalities in merosin-positive congenital muscular dystrophy. Author(s): Philpot J, Pennock J, Cowan F, Sewry CA, Dubowitz V, Bydder G, Muntoni F. Source: European Journal of Paediatric Neurology : Ejpn : Official Journal of the European Paediatric Neurology Society. 2000; 4(3): 109-14. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10872105&dopt=Abstract
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Brain MR in Fukuyama congenital muscular dystrophy. Author(s): Aida N, Tamagawa K, Takada K, Yagishita A, Kobayashi N, Chikumaru K, Iwamoto H. Source: Ajnr. American Journal of Neuroradiology. 1996 April; 17(4): 605-13. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=8730178&dopt=Abstract
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Breached cerebral glia limitans-basal lamina complex in Fukuyama-type congenital muscular dystrophy. Author(s): Saito Y, Murayama S, Kawai M, Nakano I. Source: Acta Neuropathologica. 1999 October; 98(4): 330-6. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10502035&dopt=Abstract
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Brief report: deficiency of a dystrophin-associated glycoprotein (adhalin) in a patient with muscular dystrophy and cardiomyopathy. Author(s): Fadic R, Sunada Y, Waclawik AJ, Buck S, Lewandoski PJ, Campbell KP, Lotz BP. Source: The New England Journal of Medicine. 1996 February 8; 334(6): 362-6. Erratum In: N Engl J Med 1996 March 28; 334(13): 871. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=8538707&dopt=Abstract
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Broader clinical spectrum of Fukuyama-type congenital muscular dystrophy manifested by haplotype analysis. Author(s): Yoshioka M, Toda T, Kuroki S, Hamano K. Source: Journal of Child Neurology. 1999 November; 14(11): 711-5. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10593547&dopt=Abstract
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Building the French Muscular Dystrophy Association: the role of doctor/patient interactions. Author(s): Bach MA. Source: Social History of Medicine : the Journal of the Society for the Social History of Medicine / Sshm. 1998 August; 11(2): 233-53. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11620429&dopt=Abstract
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Calcium currents and transients in co-cultured contracting normal and Duchenne muscular dystrophy human myotubes. Author(s): Imbert N, Vandebrouck C, Duport G, Raymond G, Hassoni AA, Constantin B, Cullen MJ, Cognard C. Source: The Journal of Physiology. 2001 July 15; 534(Pt. 2): 343-55. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11454955&dopt=Abstract
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Calpain 3 gene mutations: genetic and clinico-pathologic findings in limb-girdle muscular dystrophy. Author(s): Chae J, Minami N, Jin Y, Nakagawa M, Murayama K, Igarashi F, Nonaka I. Source: Neuromuscular Disorders : Nmd. 2001 September; 11(6-7): 547-55. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11525884&dopt=Abstract
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Cardiac arrest during major spinal scoliosis surgery in a patient with Duchenne's muscular dystrophy undergoing intravenous anaesthesia. Author(s): Irwin MG, Henderson M. Source: Anaesthesia and Intensive Care. 1995 October; 23(5): 626-9. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=8787270&dopt=Abstract
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Cardiac involvement in myotonic dystrophy, Becker muscular dystrophy and mitochondrial myopathy: a five-year follow-up. Author(s): Finsterer J, Stollberger C, Blazek G, Spahits E. Source: The Canadian Journal of Cardiology. 2001 October; 17(10): 1061-9. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11694896&dopt=Abstract
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Cardiac-restricted ankyrin-repeated protein is differentially induced in duchenne and congenital muscular dystrophy. Author(s): Nakada C, Tsukamoto Y, Oka A, Nonaka I, Takeda S, Sato K, Mori S, Ito H, Moriyama M. Source: Laboratory Investigation; a Journal of Technical Methods and Pathology. 2003 May; 83(5): 711-9. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12746480&dopt=Abstract
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Cardiomyopathy and atrioventricular block in Emery-Dreifuss muscular dystrophy--a case report. Author(s): Kanada M, Demirtas M, Guzel R, San M, Tuncer I. Source: Angiology. 2002 January-February; 53(1): 109-12. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11863303&dopt=Abstract
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Cardiomyopathy in a carrier of Duchenne's muscular dystrophy. Author(s): Davies JE, Winokur TS, Aaron MF, Benza RL, Foley BA, Holman WL. Source: The Journal of Heart and Lung Transplantation : the Official Publication of the International Society for Heart Transplantation. 2001 July; 20(7): 781-4. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11448811&dopt=Abstract
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Cardiomyopathy in animal models of muscular dystrophy. Author(s): Heydemann A, Wheeler MT, McNally EM. Source: Current Opinion in Cardiology. 2001 May; 16(3): 211-7. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11357018&dopt=Abstract
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Cardiomyopathy may be the only clinical manifestation in female carriers of Duchenne muscular dystrophy. Author(s): Mirabella M, Servidei S, Manfredi G, Ricci E, Frustaci A, Bertini E, Rana M, Tonali P. Source: Neurology. 1993 November; 43(11): 2342-5. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=8232953&dopt=Abstract
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Cardiovascular autonomic control in Becker muscular dystrophy. Author(s): Vita G, Di Leo R, De Gregorio C, Papalia A, Rodolico C, Coglitore S, Messina C. Source: Journal of the Neurological Sciences. 2001 May 1; 186(1-2): 45-9. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11412871&dopt=Abstract
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Carrier detection and prenatal diagnosis in Duchenne/Becker muscular dystrophy. Author(s): Panigrahi I, Mittal B. Source: Indian Pediatrics. 2001 June; 38(6): 631-9. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11418728&dopt=Abstract
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Carrier detection and prenatal molecular diagnosis in a Duchenne muscular dystrophy family without any affected relative available. Author(s): Alcantara MA, Garcia-Cavazos R, Hernandez-U E, Gonzalez-del Angel A, Carnevale A, Orozco L. Source: Annales De Genetique. 2001 July-September; 44(3): 149-53. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11694228&dopt=Abstract
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Carrier detection in non-deletional Duchenne/Becker muscular dystrophy families using polymorphic dinucleotide (CA) repeat loci of dystrophin gene. Author(s): Chaturvedi LS, Srivastava S, Mukherjee M, Mittal RD, Phadke SR, Pradhan S, Mittal B. Source: The Indian Journal of Medical Research. 2001 January; 113: 19-25. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11280167&dopt=Abstract
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Carrier detection of Duchenne/Becker muscular dystrophy by using fluorescent linkage analysis in Taiwan. Author(s): Lee CC, Wu MC, Wu JY, Li TC, Tsai FJ, Tsai CH. Source: Acta Paediatr Taiwan. 2000 March-April; 41(2): 69-74. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10927942&dopt=Abstract
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Caspase 3 expression correlates with skeletal muscle apoptosis in Duchenne and facioscapulo human muscular dystrophy. A potential target for pharmacological treatment? Author(s): Sandri M, El Meslemani AH, Sandri C, Schjerling P, Vissing K, Andersen JL, Rossini K, Carraro U, Angelini C. Source: Journal of Neuropathology and Experimental Neurology. 2001 March; 60(3): 302-12. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11245214&dopt=Abstract
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Cause of progression in Duchenne muscular dystrophy: impaired differentiation more probable than replicative aging. Author(s): Oexle K, Kohlschutter A. Source: Neuropediatrics. 2001 June; 32(3): 123-9. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11521207&dopt=Abstract
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Caveolae and caveolin-3 in muscular dystrophy. Author(s): Galbiati F, Razani B, Lisanti MP. Source: Trends in Molecular Medicine. 2001 October; 7(10): 435-41. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11597517&dopt=Abstract
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Caveolin proteins in signaling, oncogenic transformation and muscular dystrophy. Author(s): Razani B, Schlegel A, Lisanti MP. Source: Journal of Cell Science. 2000 June; 113 ( Pt 12): 2103-9. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10825283&dopt=Abstract
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CDNA microarray analysis of gene expression in fibroblasts of patients with X-linked Emery-Dreifuss muscular dystrophy. Author(s): Tsukahara T, Tsujino S, Arahata K. Source: Muscle & Nerve. 2002 June; 25(6): 898-901. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12115980&dopt=Abstract
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Changes in spirometry over time as a prognostic marker in patients with Duchenne muscular dystrophy. Author(s): Phillips MF, Quinlivan RC, Edwards RH, Calverley PM. Source: American Journal of Respiratory and Critical Care Medicine. 2001 December 15; 164(12): 2191-4. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11751186&dopt=Abstract
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Changes of laminin beta 2 chain expression in congenital muscular dystrophy. Author(s): Cohn RD, Herrmann R, Wewer UM, Voit T. Source: Neuromuscular Disorders : Nmd. 1997 September; 7(6-7): 373-8. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=9327401&dopt=Abstract
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Charles Bell (1774-1842) and an early case of muscular dystrophy. The Third Meryon Society Lecture read at Worcester College, Oxford on 28 July, 2000. Author(s): Gardner-Thorpe C. Source: Neuromuscular Disorders : Nmd. 2002 March; 12(3): 318-21. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11801406&dopt=Abstract
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Circadian rhythm and variability of heart rate in Duchenne-type progressive muscular dystrophy. Author(s): Yotsukura M, Sasaki K, Kachi E, Sasaki A, Ishihara T, Ishikawa K. Source: The American Journal of Cardiology. 1995 November 1; 76(12): 947-51. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=7484837&dopt=Abstract
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Clinical and experimental results on cardiac troponin expression in Duchenne muscular dystrophy. Author(s): Hammerer-Lercher A, Erlacher P, Bittner R, Korinthenberg R, Skladal D, Sorichter S, Sperl W, Puschendorf B, Mair J. Source: Clinical Chemistry. 2001 March; 47(3): 451-8. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11238296&dopt=Abstract
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Clinical and histopathological study of merosin-deficient and merosin-positive congenital muscular dystrophy. Author(s): Talim B, Kale G, Topaloglu H, Akcoren Z, Caglar M, Gogus S, Elkay M. Source: Pediatric and Developmental Pathology : the Official Journal of the Society for Pediatric Pathology and the Paediatric Pathology Society. 2000 March-April; 3(2): 168-76. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10679036&dopt=Abstract
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Clinical and imaging findings in six cases of congenital muscular dystrophy with rigid spine syndrome linked to chromosome 1p (RSMD1). Author(s): Mercuri E, Talim B, Moghadaszadeh B, Petit N, Brockington M, Counsell S, Guicheney P, Muntoni F, Merlini L. Source: Neuromuscular Disorders : Nmd. 2002 October; 12(7-8): 631-8. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12207930&dopt=Abstract
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Clinical and molecular genetic spectrum of autosomal dominant Emery-Dreifuss muscular dystrophy due to mutations of the lamin A/C gene. Author(s): Bonne G, Mercuri E, Muchir A, Urtizberea A, Becane HM, Recan D, Merlini L, Wehnert M, Boor R, Reuner U, Vorgerd M, Wicklein EM, Eymard B, Duboc D, Penisson-Besnier I, Cuisset JM, Ferrer X, Desguerre I, Lacombe D, Bushby K, Pollitt C, Toniolo D, Fardeau M, Schwartz K, Muntoni F. Source: Annals of Neurology. 2000 August; 48(2): 170-80. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10939567&dopt=Abstract
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Clinical and molecular studies in a unique family with autosomal dominant limbgirdle muscular dystrophy and Paget disease of bone. Author(s): Kimonis VE, Kovach MJ, Waggoner B, Leal S, Salam A, Rimer L, Davis K, Khardori R, Gelber D. Source: Genetics in Medicine : Official Journal of the American College of Medical Genetics. 2000 July-August; 2(4): 232-41. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11252708&dopt=Abstract
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Clinical and molecular study in congenital muscular dystrophy with partial laminin alpha 2 (LAMA2) deficiency. Author(s): Tezak Z, Prandini P, Boscaro M, Marin A, Devaney J, Marino M, Fanin M, Trevisan CP, Park J, Tyson W, Finkel R, Garcia C, Angelini C, Hoffman EP, Pegoraro E. Source: Human Mutation. 2003 February; 21(2): 103-11. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12552556&dopt=Abstract
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Clinical relevance of atrial fibrillation/flutter, stroke, pacemaker implant, and heart failure in Emery-Dreifuss muscular dystrophy: a long-term longitudinal study. Author(s): Boriani G, Gallina M, Merlini L, Bonne G, Toniolo D, Amati S, Biffi M, Martignani C, Frabetti L, Bonvicini M, Rapezzi C, Branzi A. Source: Stroke; a Journal of Cerebral Circulation. 2003 April; 34(4): 901-8. Epub 2003 March 20. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12649505&dopt=Abstract
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Clinical results of early orthopaedic management in Duchenne muscular dystrophy. Author(s): Goertzen M, Baltzer A, Voit T. Source: Neuropediatrics. 1995 October; 26(5): 257-9. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=8552216&dopt=Abstract
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Clinical significance of late potential in patients with Duchenne muscular dystrophy. Author(s): Kubo M, Matsuoka S, Taguchi Y, Akita H, Kuroda Y. Source: Pediatric Cardiology. 1993 October; 14(4): 214-9. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=8255794&dopt=Abstract
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Clinical variability and molecular diagnosis in a four-generation family with Xlinked Emery-Dreifuss muscular dystrophy. Author(s): Canki-Klain N, Recan D, Milicic D, Llense S, Leturcq F, Deburgrave N, Kaplan JC, Debevec M, Zurak N. Source: Croatian Medical Journal. 2000 December; 41(4): 389-95. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11063761&dopt=Abstract
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Clinicopathological study on eyes from cases of Fukuyama type congenital muscular dystrophy. Author(s): Hino N, Kobayashi M, Shibata N, Yamamoto T, Saito K, Osawa M. Source: Brain & Development. 2001 March; 23(2): 97-107. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11248458&dopt=Abstract
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Coagulation and fibrinolysis disorder in muscular dystrophy. Author(s): Saito T, Takenaka M, Miyai I, Yamamoto Y, Matsumura T, Nozaki S, Kang J. Source: Muscle & Nerve. 2001 March; 24(3): 399-402. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11353426&dopt=Abstract
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Coats' disease and Duchenne muscular dystrophy. Author(s): Bobart A, Brosnahan D. Source: Eye (London, England). 2001 August; 15(Pt 4): 563-4. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11767047&dopt=Abstract
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Collaborative translational research leading to multicenter clinical trials in Duchenne muscular dystrophy: the Cooperative International Neuromuscular Research Group (CINRG). Author(s): Escolar DM, Henricson EK, Pasquali L, Gorni K, Hoffman EP. Source: Neuromuscular Disorders : Nmd. 2002 October; 12 Suppl 1: S147-154. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12206809&dopt=Abstract
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Collagen type VI and related disorders: Bethlem myopathy and Ullrich scleroatonic muscular dystrophy. Author(s): Bertini E, Pepe G. Source: European Journal of Paediatric Neurology : Ejpn : Official Journal of the European Paediatric Neurology Society. 2002; 6(4): 193-8. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12374585&dopt=Abstract
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Comparative analysis of PCR-deletion detection and immunohistochemistry in Brazilian Duchenne and Becker muscular dystrophy patients. Author(s): Werneck LC, Scola RH, Maegawa GH, Werneck MC. Source: American Journal of Medical Genetics. 2001 October 1; 103(2): 115-20. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11568916&dopt=Abstract
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Complete allele information in the diagnosis of facioscapulohumeral muscular dystrophy by triple DNA analysis. Author(s): Lemmers RJL, de Kievit P, van Geel M, van der Wielen MJ, Bakker E, Padberg GW, Frants RR, van der Maarel SM. Source: Annals of Neurology. 2001 December; 50(6): 816-9. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11761483&dopt=Abstract
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Complete skipping of exon 66 due to novel mutations of the dystrophin gene was identified in two Japanese families of Duchenne muscular dystrophy with severe mental retardation. Author(s): Wibawa T, Takeshima Y, Mitsuyoshi I, Wada H, Surono A, Nakamura H, Matsuo M. Source: Brain & Development. 2000 March; 22(2): 107-12. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10722962&dopt=Abstract
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Confirmation of linkage of oculopharyngeal muscular dystrophy to chromosome 14q11.2-q13 in American families suggests the existence of a second causal mutation. Author(s): Stajich JM, Gilchrist JM, Lennon F, Lee A, Yamaoka L, Rosi B, Gaskell PC, Pritchard M, Donald L, Roses AD, Vance JM, Pericak-Vance MA. Source: Neuromuscular Disorders : Nmd. 1997 October; 7 Suppl 1: S75-81. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=9392021&dopt=Abstract
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Confocal analysis of the dystrophin protein complex in muscular dystrophy. Author(s): Draviam R, Billington L, Senchak A, Hoffman EP, Watkins SC. Source: Muscle & Nerve. 2001 February; 24(2): 262-72. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11180210&dopt=Abstract
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Congenital muscular dystrophy associated with calf hypertrophy, microcephaly and severe mental retardation in three Italian families: evidence for a novel CMD syndrome. Author(s): Villanova M, Mercuri E, Bertini E, Sabatelli P, Morandi L, Mora M, Sewry C, Brockington M, Brown SC, Ferreiro A, Maraldi NM, Toda T, Guicheney P, Merlini L, Muntoni F. Source: Neuromuscular Disorders : Nmd. 2000 December; 10(8): 541-7. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11053679&dopt=Abstract
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Congenital muscular dystrophy in Israeli families. Author(s): Rachmiel M, Nevo Y, Lahat E, Kutai M, Harel S, Shahar E. Source: Journal of Child Neurology. 2002 May; 17(5): 333-6. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12150578&dopt=Abstract
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Congenital muscular dystrophy with adducted thumbs, ptosis, external ophthalmoplegia, mental retardation and cerebellar hypoplasia: a novel form of CMD. Author(s): Voit T, Parano E, Straub V, Schroder JM, Schaper J, Pavone P, Falsaperla R, Pavone L, Herrmann R. Source: Neuromuscular Disorders : Nmd. 2002 October; 12(7-8): 623-30. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12207929&dopt=Abstract
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Congenital muscular dystrophy with central and peripheral nervous system involvement in a Belgian patient. Author(s): Belpaire-Dethiou MC, Saito K, Fukuyama Y, Kondo-Iida E, Toda T, Duprez T, Verellen-Dumoulin C, Van den Bergh PY. Source: Neuromuscular Disorders : Nmd. 1999 June; 9(4): 251-6. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10399753&dopt=Abstract
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Congenital muscular dystrophy with partial deficiency of merosin. Author(s): Tachi N, Kamimura S, Ohya K, Chiba S, Sasaki K. Source: Journal of the Neurological Sciences. 1997 October 3; 151(1): 25-7. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=9335006&dopt=Abstract
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Congenital muscular dystrophy with primary partial laminin alpha2 chain deficiency: molecular study. Author(s): He Y, Jones KJ, Vignier N, Morgan G, Chevallay M, Barois A, EstournetMathiaud B, Hori H, Mizuta T, Tome FM, North KN, Guicheney P. Source: Neurology. 2001 October 9; 57(7): 1319-22. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11591858&dopt=Abstract
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Congenital muscular dystrophy with secondary merosin deficiency and normal brain MRI: a novel entity? Author(s): Mercuri E, Sewry CA, Brown SC, Brockington M, Jungbluth H, DeVile C, Counsell S, Manzur A, Muntoni F. Source: Neuropediatrics. 2000 August; 31(4): 186-9. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11071142&dopt=Abstract
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Congenital muscular dystrophy. Author(s): Huang FL, Mak SC, Chi CS. Source: Zhonghua Yi Xue Za Zhi (Taipei). 2000 February; 63(2): 165-9. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10677931&dopt=Abstract
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Congenital muscular dystrophy: searching for a definition after 98 years. Author(s): Mendell JR. Source: Neurology. 2001 April 24; 56(8): 993-4. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11320168&dopt=Abstract
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Contrasting evolutionary histories of two introns of the duchenne muscular dystrophy gene, Dmd, in humans. Author(s): Nachman MW, Crowell SL. Source: Genetics. 2000 August; 155(4): 1855-64. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10924480&dopt=Abstract
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Controversial muscular dystrophy therapy goes to court. Author(s): Birmingham K. Source: Nature Medicine. 1997 October; 3(10): 1058. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=9334704&dopt=Abstract
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Correction of blepharoptosis in oculopharyngeal muscular dystrophy. Author(s): Kang DH, Koo SH, Ahn DS, Park SH, Yoon ES. Source: Annals of Plastic Surgery. 2002 October; 49(4): 419-23. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12370650&dopt=Abstract
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Correlation between progression of spinal deformity and pulmonary function in Duchenne muscular dystrophy. Author(s): Yamashita T, Kanaya K, Yokogushi K, Ishikawa Y, Minami R. Source: Journal of Pediatric Orthopedics. 2001 January-February; 21(1): 113-6. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11176364&dopt=Abstract
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Correlation of clinical function and muscle CT scan images in limb-girdle muscular dystrophy. Author(s): Vlak M, van der Kooi E, Angelini C. Source: Neurological Sciences : Official Journal of the Italian Neurological Society and of the Italian Society of Clinical Neurophysiology. 2000; 21(5 Suppl): S975-7. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11382199&dopt=Abstract
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Correlation of laboratory and clinical findings with the location of Xp21 deletion in Duchenne muscular dystrophy. Author(s): Tasdemir HA, Topaloglu H, Dincer P, Gogus S, Kotiloglu E, Ozdirim E, Yalaz K. Source: Turk J Pediatr. 1997 July-September; 39(3): 317-24. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=9339110&dopt=Abstract
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Daytime predictors of sleep hypoventilation in Duchenne muscular dystrophy. Author(s): Hukins CA, Hillman DR. Source: American Journal of Respiratory and Critical Care Medicine. 2000 January; 161(1): 166-70. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10619815&dopt=Abstract
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De novo facioscapulohumeral muscular dystrophy: frequent somatic mosaicism, sexdependent phenotype, and the role of mitotic transchromosomal repeat interaction between chromosomes 4 and 10. Author(s): van der Maarel SM, Deidda G, Lemmers RJ, van Overveld PG, van der Wielen M, Hewitt JE, Sandkuijl L, Bakker B, van Ommen GJ, Padberg GW, Frants RR. Source: American Journal of Human Genetics. 2000 January; 66(1): 26-35. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10631134&dopt=Abstract
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Decreased bone density in ambulatory patients with duchenne muscular dystrophy. Author(s): Aparicio LF, Jurkovic M, DeLullo J. Source: Journal of Pediatric Orthopedics. 2002 March-April; 22(2): 179-81. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11856925&dopt=Abstract
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Decreased sperm function of patients with myotonic muscular dystrophy. Author(s): Hortas ML, Castilla JA, Gil MT, Molina J, Garrido ML, Morell M, Redondo M. Source: Human Reproduction (Oxford, England). 2000 February; 15(2): 445-8. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10655320&dopt=Abstract
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Defective expression of plectin/HD1 in epidermolysis bullosa simplex with muscular dystrophy. Author(s): Gache Y, Chavanas S, Lacour JP, Wiche G, Owaribe K, Meneguzzi G, Ortonne JP. Source: The Journal of Clinical Investigation. 1996 May 15; 97(10): 2289-98. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=8636409&dopt=Abstract
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Defective glycosylation in muscular dystrophy. Author(s): Muntoni F, Brockington M, Blake DJ, Torelli S, Brown SC. Source: Lancet. 2002 November 2; 360(9343): 1419-21. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12424008&dopt=Abstract
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Defective growth in vitro of Duchenne Muscular Dystrophy myoblasts: the molecular and biochemical basis. Author(s): Melone MA, Peluso G, Petillo O, Galderisi U, Cotrufo R. Source: Journal of Cellular Biochemistry. 1999 November; 76(1): 118-32. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10581006&dopt=Abstract
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Deficiency of the 50 kDa dystrophin-associated-glycoprotein (adhalin) in an Indian autosomal recessive limb girdle muscular dystrophy patient : immunochemical analysis and clinical aspects. Author(s): Handa V, Mital A, Gupta M, Goyle S. Source: Neurology India. 2001 March; 49(1): 19-24. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11303236&dopt=Abstract
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Deflazacort treatment of Duchenne muscular dystrophy. Author(s): Biggar WD, Gingras M, Fehlings DL, Harris VA, Steele CA. Source: The Journal of Pediatrics. 2001 January; 138(1): 45-50. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11148511&dopt=Abstract
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Delayed diagnosis of Duchenne muscular dystrophy. Author(s): Mohamed K, Appleton R, Nicolaides P. Source: European Journal of Paediatric Neurology : Ejpn : Official Journal of the European Paediatric Neurology Society. 2000; 4(5): 219-23. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11030068&dopt=Abstract
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Deletion screening and carrier detection in Duchenne muscular dystrophy in Polish population via direct analysis of DNA and RNA transcripts. Author(s): Kwiatkowska J, Lisiecka D, Sowinska J, Marszal E, Emich-Widera E, Ciesielski T, Szczegola-Przymusiak A, Nuc P, Chlebowska H, Zimowski J, GalasZgorzalewicz B, Slomski R. Source: Biochimie. 1997 July; 79(7): 439-48. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=9352094&dopt=Abstract
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Denaturing gradient gel electrophoresis (DGGE) for mutation detection in Duchenne muscular dystrophy (DMD). Author(s): Dolinsky LC. Source: Methods in Molecular Biology (Clifton, N.J.). 2003; 217: 165-75. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12491931&dopt=Abstract
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Dental characteristics of patients with Duchenne muscular dystrophy. Author(s): Symons AL, Townsend GC, Hughes TE. Source: Asdc J Dent Child. 2002 September-December; 69(3): 277-83, 234. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12613312&dopt=Abstract
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Depressed myocardial fatty acid metabolism in patients with muscular dystrophy. Author(s): Momose M, Iguchi N, Imamura K, Usui H, Ueda T, Miyamoto K, Inaba S. Source: Neuromuscular Disorders : Nmd. 2001 July; 11(5): 464-9. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11404118&dopt=Abstract
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Detection of 1583 bp gene transcript in lymphocytes of muscular dystrophy patients. Author(s): Prabhakar S, Anand A. Source: Neurology India. 2002 December; 50(4): 537-8. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12577122&dopt=Abstract
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Detection of gene deletions in Chinese patients with Duchenne/Becker muscular dystrophy using CDNA probes and the polymerase chain reaction method. Author(s): Yuge L, Hui L, Bingdi X. Source: Life Sciences. 1999; 65(9): 863-9. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10465346&dopt=Abstract
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Deterioration of lung function and scoliosis in Duchenne muscular dystrophy. Author(s): Galasko SB. Source: Journal of Pediatric Orthopedics. 2001 November-December; 21(6): 827-8. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11675569&dopt=Abstract
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Developmental expression of myotilin, a gene mutated in limb-girdle muscular dystrophy type 1A. Author(s): Mologni L, Salmikangas P, Fougerousse F, Beckmann JS, Carpen O. Source: Mechanisms of Development. 2001 May; 103(1-2): 121-5. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11335118&dopt=Abstract
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Developments in gene therapy for muscular dystrophy. Author(s): Hartigan-O'Connor D, Chamberlain JS. Source: Microscopy Research and Technique. 2000 February 1-15; 48(3-4): 223-38. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10679969&dopt=Abstract
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Diaphragm kinetics during pneumatic belt respiratory assistance: a sonographic study in Duchenne muscular dystrophy. Author(s): Ayoub J, Milane J, Targhetta R, Prioux J, Chamari K, Arbeille P, Jonquet O, Bourgeois JM, Prefaut C. Source: Neuromuscular Disorders : Nmd. 2002 August; 12(6): 569-75. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12117482&dopt=Abstract
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Different mutations in the LMNA gene cause autosomal dominant and autosomal recessive Emery-Dreifuss muscular dystrophy. Author(s): Raffaele Di Barletta M, Ricci E, Galluzzi G, Tonali P, Mora M, Morandi L, Romorini A, Voit T, Orstavik KH, Merlini L, Trevisan C, Biancalana V, HousmanowaPetrusewicz I, Bione S, Ricotti R, Schwartz K, Bonne G, Toniolo D. Source: American Journal of Human Genetics. 2000 April; 66(4): 1407-12. Epub 2000 March 16. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10739764&dopt=Abstract
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Dilated cardiomyopathy of Becker-type muscular dystrophy with exon 4 deletion--a case report. Author(s): Saotome M, Yoshitomi Y, Kojima S, Kuramochi M. Source: Angiology. 2001 May; 52(5): 343-7. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11386386&dopt=Abstract
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Direct detection of 4q35 rearrangements implicated in facioscapulohumeral muscular dystrophy (FSHD). Author(s): Deidda G, Cacurri S, Piazzo N, Felicetti L. Source: Journal of Medical Genetics. 1996 May; 33(5): 361-5. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=8733043&dopt=Abstract
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Disabilities in children with Duchenne muscular dystrophy: a profile. Author(s): Nair KP, Vasanth A, Gourie-Devi M, Taly AB, Rao S, Gayathri N, Murali T. Source: Journal of Rehabilitation Medicine : Official Journal of the Uems European Board of Physical and Rehabilitation Medicine. 2001 July; 33(4): 147-9. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11506211&dopt=Abstract
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Disability, coping and quality of life in individuals with muscular dystrophy: a prospective study over five years. Author(s): Natterlund B, Gunnarsson LG, Ahlstrom G. Source: Disability and Rehabilitation. 2000 November 20; 22(17): 776-85. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11194618&dopt=Abstract
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Disease taxonomy--monogenic muscular dystrophy. Author(s): Beckmann JS. Source: British Medical Bulletin. 1999; 55(2): 340-57. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10723861&dopt=Abstract
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Disorganization of the desmin cytoskeleton and mitochondrial dysfunction in plectin-related epidermolysis bullosa simplex with muscular dystrophy. Author(s): Schroder R, Kunz WS, Rouan F, Pfendner E, Tolksdorf K, Kappes-Horn K, Altenschmidt-Mehring M, Knoblich R, van der Ven PF, Reimann J, Furst DO, Blumcke I, Vielhaber S, Zillikens D, Eming S, Klockgether T, Uitto J, Wiche G, Rolfs A. Source: Journal of Neuropathology and Experimental Neurology. 2002 June; 61(6): 52030. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12071635&dopt=Abstract
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Dissociation of the dystroglycan complex in caveolin-3-deficient limb girdle muscular dystrophy. Author(s): Herrmann R, Straub V, Blank M, Kutzick C, Franke N, Jacob EN, Lenard HG, Kroger S, Voit T. Source: Human Molecular Genetics. 2000 September 22; 9(15): 2335-40. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11001938&dopt=Abstract
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Distal anterior compartment myopathy: a dysferlin mutation causing a new muscular dystrophy phenotype. Author(s): Illa I, Serrano-Munuera C, Gallardo E, Lasa A, Rojas-Garcia R, Palmer J, Gallano P, Baiget M, Matsuda C, Brown RH. Source: Annals of Neurology. 2001 January; 49(1): 130-4. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11198284&dopt=Abstract
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Distal muscular dystrophy of the Miyoshi type. Author(s): Yildiz H, Emre U, Coskun O, Ergun U, Atasoy HT, Inan LE. Source: Clin Neuropathol. 2003 July-August; 22(4): 204-8. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12908758&dopt=Abstract
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Distinguishing cardiac features of a novel form of congenital muscular dystrophy (Salih cmd). Author(s): Subahi SA. Source: Pediatric Cardiology. 2001 July-August; 22(4): 297-301. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11455396&dopt=Abstract
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Do some genetic mutations predict the development of dilated cardiomyopathy in patients with Becker's muscular dystrophy? Author(s): Ozdemir O, Arda K, Soylu M, Kutuk E. Source: Angiology. 2003 May-June; 54(3): 383-4. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12785035&dopt=Abstract
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Down-regulation of an ankyrin repeat-containing protein, V-1, during skeletal muscle differentiation and its re-expression in the regenerative process of muscular dystrophy. Author(s): Furukawa Y, Hashimoto N, Yamakuni T, Ishida Y, Kato C, Ogashiwa M, Kobayashi M, Kobayashi T, Nonaka I, Mizusawa H, Song SY. Source: Neuromuscular Disorders : Nmd. 2003 January; 13(1): 32-41. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12467730&dopt=Abstract
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Duchenne and Becker muscular dystrophy: from gene diagnosis to molecular therapy. Author(s): Matsuo M. Source: Iubmb Life. 2002 March; 53(3): 147-52. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12102170&dopt=Abstract
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Duchenne muscular dystrophy improved by gentamicin. Author(s): Senior K. Source: Molecular Medicine Today. 1999 November; 5(11): 461. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10529784&dopt=Abstract
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Duchenne muscular dystrophy in a female child. Author(s): Viswanathan V. Source: Indian Pediatrics. 2002 October; 39(10): 980-1; Author Reply 981. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12428052&dopt=Abstract
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Duchenne muscular dystrophy in a female child. Author(s): Joshi S. Source: Indian Pediatrics. 2002 January; 39(1): 98. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11805363&dopt=Abstract
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Duchenne muscular dystrophy or Meryon's disease. Author(s): Emery A. Source: Lancet. 2001 May 12; 357(9267): 1529. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11383539&dopt=Abstract
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Duchenne muscular dystrophy. Author(s): Sussman M. Source: J Am Acad Orthop Surg. 2002 March-April; 10(2): 138-51. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11929208&dopt=Abstract
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Duchenne muscular dystrophy. Author(s): Metules T. Source: Rn. 2002 October; 65(10): 39-44, 47; Quiz 48. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12432710&dopt=Abstract
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Duchenne muscular dystrophy. Author(s): Ishikawa Y, Bach JR. Source: Thorax. 1999 June; 54(6): 564. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10866575&dopt=Abstract
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Duchenne muscular dystrophy. Author(s): Dickson G, Brown SC. Source: Mol Cell Biol Hum Dis Ser. 1995; 5: 261-80. Review. No Abstract Available. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=9532571&dopt=Abstract
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Duchenne muscular dystrophy. See me graduate. Author(s): Verberkt HJ. Source: Lancet. 2001 December; 358 Suppl: S26. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11784575&dopt=Abstract
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Duchenne muscular dystrophy: current knowledge, treatment, and future prospects. Author(s): Biggar WD, Klamut HJ, Demacio PC, Stevens DJ, Ray PN. Source: Clinical Orthopaedics and Related Research. 2002 August; (401): 88-106. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12151886&dopt=Abstract
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Duchenne muscular dystrophy: lack of differences in the expression of endogenous carbohydrate- and heparin-binding proteins (lectins) in cultured fibroblasts. Author(s): Stulnig T, Schweiger M, Hirsch-Kauffmann M. Source: European Journal of Cell Biology. 1993 October; 62(1): 173-81. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=8269975&dopt=Abstract
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Duchenne muscular dystrophy: prolongation of life by noninvasive ventilation and mechanically assisted coughing. Author(s): Gomez-Merino E, Bach JR. Source: American Journal of Physical Medicine & Rehabilitation / Association of Academic Physiatrists. 2002 June; 81(6): 411-5. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12023596&dopt=Abstract
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Duchenne muscular dystrophy: relevant paper was not included. Author(s): Smith RA, Phillips RS. Source: Bmj (Clinical Research Ed.). 2001 November 24; 323(7323): 1253. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11719423&dopt=Abstract
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Duchenne muscular dystrophy-rhabdomyosarcoma, ichthyosis vulgaris/acute monoblastic leukemia: association of rare genetic disorders and childhood malignant diseases. Author(s): Jakab Z, Szegedi I, Balogh E, Kiss C, Olah E. Source: Medical and Pediatric Oncology. 2002 July; 39(1): 66-8. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12116087&dopt=Abstract
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Duchenne/Becker muscular dystrophy: correlation of phenotype by electroretinography with sites of dystrophin mutations. Author(s): Pillers DM, Fitzgerald KM, Duncan NM, Rash SM, White RA, Dwinnell SJ, Powell BR, Schnur RE, Ray PN, Cibis GW, Weleber RG. Source: Human Genetics. 1999 July-August; 105(1-2): 2-9. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10480348&dopt=Abstract
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Duchenne/Becker muscular dystrophy: from molecular diagnosis to gene therapy. Author(s): Matsuo M. Source: Brain & Development. 1996 May-June; 18(3): 167-72. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=8836495&dopt=Abstract
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Duchenne-Becker muscular dystrophy and the nondystrophic myotonias. Paradigms for loss of function and change of function of gene products. Author(s): Hoffman EP, Wang J. Source: Archives of Neurology. 1993 November; 50(11): 1227-37. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=8215981&dopt=Abstract
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Duplication detection in Japanese Duchenne muscular dystrophy patients and identification of carriers with partial gene deletions using pulsed-field gel electrophoresis. Author(s): Kodaira M, Hiyama K, Karakawa T, Kameo H, Satoh C. Source: Human Genetics. 1993 October 1; 92(3): 237-43. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=8406431&dopt=Abstract
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Dysferlin and muscular dystrophy. Author(s): Bushby KM. Source: Acta Neurol Belg. 2000 September; 100(3): 142-5. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11098285&dopt=Abstract
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Dysmyelinating sensory-motor neuropathy in merosin-deficient congenital muscular dystrophy. Author(s): Di Muzio A, De Angelis MV, Di Fulvio P, Ratti A, Pizzuti A, Stuppia L, Gambi D, Uncini A. Source: Muscle & Nerve. 2003 April; 27(4): 500-6. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12661054&dopt=Abstract
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Dystrophin and muscular dystrophy: past, present, and future. Author(s): O'Brien KF, Kunkel LM. Source: Molecular Genetics and Metabolism. 2001 September-October; 74(1-2): 75-88. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11592805&dopt=Abstract
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Dystrophinopathy in isolated female patients with muscular dystrophy. Author(s): Serdaroglu A, Kotiloglu E, Caglar M, Topaloglu H. Source: Pediatric Pathology & Laboratory Medicine : Journal of the Society for Pediatric Pathology, Affiliated with the International Paediatric Pathology Association. 1996 MayJune; 16(3): 393-402. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=9025841&dopt=Abstract
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Early and severe presentation of autosomal dominant Emery-Dreifuss muscular dystrophy (EMD2). Author(s): Mercuri E, Manzur AY, Jungbluth H, Bonne G, Muchir A, Sewry C, Schwartz K, Muntoni F. Source: Neurology. 2000 April 25; 54(8): 1704-5. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10762524&dopt=Abstract
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Early cardiac failure in a child with Becker muscular dystrophy is due to an abnormally low amount of dystrophin transcript lacking exon 13. Author(s): Ishigaki C, Patria SY, Nishio H, Yoshioka A, Matsuo M. Source: Acta Paediatr Jpn. 1997 December; 39(6): 685-9. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=9447758&dopt=Abstract
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Early decrease of IIx myosin heavy chain transcripts in Duchenne muscular dystrophy. Author(s): Pedemonte M, Sandri C, Schiaffino S, Minetti C. Source: Biochemical and Biophysical Research Communications. 1999 February 16; 255(2): 466-9. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10049732&dopt=Abstract
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Early diagnosis in Duchenne muscular dystrophy. Author(s): Zalaudek I, Bonelli RM, Koltringer P, Reisecker F, Wagner K. Source: Lancet. 1999 June 5; 353(9168): 1975. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10371601&dopt=Abstract
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Early diagnosis of Duchenne muscular dystrophy with high level of transaminases. Author(s): Kurul S, Ulgenalp A, Dirik E, Ercal D. Source: Indian Pediatrics. 2002 February; 39(2): 210-1. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11867860&dopt=Abstract
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Early observations on muscular dystrophy: Gowers' textbook revisited. Author(s): Pascuzzi RM. Source: Seminars in Neurology. 1999; 19(1): 87-92. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10711992&dopt=Abstract
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Early onset of cardiomyopathy in two brothers with X-linked Emery-Dreifuss muscular dystrophy. Author(s): Talkop UA, Talvik I, Sonajalg M, Sibul H, Kolk A, Piirsoo A, Warzok R, Wulff K, Wehnert MS, Talvik T. Source: Neuromuscular Disorders : Nmd. 2002 November; 12(9): 878-81. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12398842&dopt=Abstract
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Early onset of X-linked Emery-Dreifuss muscular dystrophy in a boy with emerin gene deletion. Author(s): Fujimoto S, Ishikawa T, Saito M, Wada Y, Wada I, Arahata K, Nonaka I. Source: Neuropediatrics. 1999 June; 30(3): 161-3. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10480214&dopt=Abstract
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Early onset, autosomal recessive muscular dystrophy with Emery-Dreifuss phenotype and normal emerin expression. Author(s): Taylor J, Sewry CA, Dubowitz V, Muntoni F. Source: Neurology. 1998 October; 51(4): 1116-20. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=9781539&dopt=Abstract
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Early prednisone treatment in Duchenne muscular dystrophy. Author(s): Merlini L, Cicognani A, Malaspina E, Gennari M, Gnudi S, Talim B, Franzoni E. Source: Muscle & Nerve. 2003 February; 27(2): 222-7. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12548530&dopt=Abstract
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Early presentation of X-linked Emery-Dreifuss muscular dystrophy resembling limbgirdle muscular dystrophy. Author(s): Muntoni F, Lichtarowicz-Krynska EJ, Sewry CA, Manilal S, Recan D, Llense S, Taylor J, Morris GE, Dubowitz V. Source: Neuromuscular Disorders : Nmd. 1998 April; 8(2): 72-6. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=9608559&dopt=Abstract
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Early symptoms of Duchenne muscular dystrophy--description of cases of an 18month-old and an 8-year-old patient. Author(s): Iwanczak F, Stawarski A, Potyrala M, Siedlecka-Dawidko J, Agrawal GS. Source: Medical Science Monitor : International Medical Journal of Experimental and Clinical Research. 2000 May-June; 6(3): 592-5. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11208376&dopt=Abstract
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Early ultrastructural changes in the central nervous system in Fukuyama congenital muscular dystrophy. Author(s): Yamamoto T, Shibata N, Kanazawa M, Kobayashi M, Komori T, Kondo E, Saito K, Osawa M. Source: Ultrastructural Pathology. 1997 July-August; 21(4): 355-60. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=9206000&dopt=Abstract
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Early white matter changes on brain magnetic resonance imaging in a newborn affected by merosin-deficient congenital muscular dystrophy. Author(s): Mercuri E, Rutherford M, De Vile C, Counsell S, Sewry C, Brown S, Bydder G, Dubowitz V, Muntoni F. Source: Neuromuscular Disorders : Nmd. 2001 April; 11(3): 297-9. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11297945&dopt=Abstract
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Early-onset facioscapulohumeral muscular dystrophy: two case reports. Author(s): Okinaga A, Matsuoka T, Umeda J, Yanagihara I, Inui K, Nagai T, Okada S. Source: Brain & Development. 1997 December; 19(8): 563-7. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=9440803&dopt=Abstract
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Effects of deflazacort on left ventricular function in patients with Duchenne muscular dystrophy. Author(s): Silversides CK, Webb GD, Harris VA, Biggar DW. Source: The American Journal of Cardiology. 2003 March 15; 91(6): 769-72. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12633823&dopt=Abstract
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Effects of deleting a tripeptide sequence observed in muscular dystrophy patients on the conformation of synthetic peptides corresponding to the scaffolding domain of caveolin-3. Author(s): Jagannadham MV, Sharadadevi A, Nagaraj R. Source: Biochemical and Biophysical Research Communications. 2002 October 25; 298(2): 203-6. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12387816&dopt=Abstract
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Effects of expressing lamin A mutant protein causing Emery-Dreifuss muscular dystrophy and familial partial lipodystrophy in HeLa cells. Author(s): Bechert K, Lagos-Quintana M, Harborth J, Weber K, Osborn M. Source: Experimental Cell Research. 2003 May 15; 286(1): 75-86. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12729796&dopt=Abstract
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Effects on collagen VI mRNA stability and microfibrillar assembly of three COL6A2 mutations in two families with Ullrich congenital muscular dystrophy. Author(s): Zhang RZ, Sabatelli P, Pan TC, Squarzoni S, Mattioli E, Bertini E, Pepe G, Chu ML. Source: The Journal of Biological Chemistry. 2002 November 15; 277(46): 43557-64. Epub 2002 September 05. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12218063&dopt=Abstract
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Electron microscopic examination of basal lamina in Fukuyama congenital muscular dystrophy. Author(s): Ishii H, Hayashi YK, Nonaka I, Arahata K. Source: Neuromuscular Disorders : Nmd. 1997 May; 7(3): 191-7. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=9185184&dopt=Abstract
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Electroretinogram in Duchenne/Becker muscular dystrophy. Author(s): Pascual Pascual SI, Molano J, Pascual-Castroviejo I. Source: Pediatric Neurology. 1998 April; 18(4): 315-20. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=9588526&dopt=Abstract
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Electroretinographic findings in Duchenne/Becker muscular dystrophy and correlation with genotype. Author(s): Ulgenalp A, Oner FH, Soylev MF, Bora E, Afrashi F, Kose S, Ercal D. Source: Ophthalmic Genetics. 2002 September; 23(3): 157-65. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12324874&dopt=Abstract
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Elevated aminotransferase activity as an indication of muscular dystrophy: case reports and review of the literature. Author(s): Zamora S, Adams C, Butzner JD, Machida H, Scott RB. Source: Canadian Journal of Gastroenterology = Journal Canadien De Gastroenterologie. 1996 October; 10(6): 389-93. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=9193775&dopt=Abstract
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Elevated plasma levels of transforming growth factor beta1 in patients with muscular dystrophy. Author(s): Ishitobi M, Haginoya K, Zhao Y, Ohnuma A, Minato J, Yanagisawa T, Tanabu M, Kikuchi M, Iinuma K. Source: Neuroreport. 2000 December 18; 11(18): 4033-5. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11192624&dopt=Abstract
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Emerin and cardiomyopathy in Emery-Dreifuss muscular dystrophy. Author(s): Funakoshi M, Tsuchiya Y, Arahata K. Source: Neuromuscular Disorders : Nmd. 1999 March; 9(2): 108-14. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10220866&dopt=Abstract
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Emerin, deficiency of which causes Emery-Dreifuss muscular dystrophy, is localized at the inner nuclear membrane. Author(s): Yorifuji H, Tadano Y, Tsuchiya Y, Ogawa M, Goto K, Umetani A, Asaka Y, Arahata K. Source: Neurogenetics. 1997 September; 1(2): 135-40. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10732816&dopt=Abstract
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Emery-Dreifuss muscular dystrophy - a 40 year retrospective. Author(s): Emery AE. Source: Neuromuscular Disorders : Nmd. 2000 June; 10(4-5): 228-32. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10838246&dopt=Abstract
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Emery-Dreifuss muscular dystrophy, nuclear cell signaling and chromatin remodeling. Author(s): Maraldi NM, Squarzoni S, Sabatelli P, Lattanzi G, Ognibene A, Manzoli FA. Source: Advances in Enzyme Regulation. 2002; 42: 1-18. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12123703&dopt=Abstract
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Emery-Dreifuss muscular dystrophy. Author(s): Helbling-Leclerc A, Bonne G, Schwartz K. Source: European Journal of Human Genetics : Ejhg. 2002 March; 10(3): 157-61. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11973618&dopt=Abstract
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Emery-Dreifuss muscular dystrophy. Author(s): Zacharias AS, Wagener ME, Warren ST, Hopkins LC. Source: Seminars in Neurology. 1999; 19(1): 67-79. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10711990&dopt=Abstract
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Emery-Dreifuss muscular dystrophy: anatomical-clinical correlation (case report). Author(s): Carvalho AA, Levy JA, Gutierrez PS, Marie SK, Sosa EA, Scanavaca M. Source: Arquivos De Neuro-Psiquiatria. 2000 December; 58(4): 1123-7. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11105084&dopt=Abstract
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Enhanced expression of the alpha 7 beta 1 integrin reduces muscular dystrophy and restores viability in dystrophic mice. Author(s): Burkin DJ, Wallace GQ, Nicol KJ, Kaufman DJ, Kaufman SJ. Source: The Journal of Cell Biology. 2001 March 19; 152(6): 1207-18. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11257121&dopt=Abstract
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Epidemiology and inheritance of oculopharyngeal muscular dystrophy in Israel. Author(s): Blumen SC, Nisipeanu P, Sadeh M, Asherov A, Blumen N, Wirguin Y, Khilkevich O, Carasso RL, Korczyn AD. Source: Neuromuscular Disorders : Nmd. 1997 October; 7 Suppl 1: S38-40. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=9392014&dopt=Abstract
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Epidermolysis bullosa simplex associated with muscular dystrophy: phenotypegenotype correlations and review of the literature. Author(s): Shimizu H, Takizawa Y, Pulkkinen L, Murata S, Kawai M, Hachisuka H, Udono M, Uitto J, Nishikawa T. Source: Journal of the American Academy of Dermatology. 1999 December; 41(6): 950-6. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10570379&dopt=Abstract
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Epidermolysis bullosa: novel and de novo premature termination codon and deletion mutations in the plectin gene predict late-onset muscular dystrophy. Author(s): Rouan F, Pulkkinen L, Meneguzzi G, Laforgia S, Hyde P, Kim DU, Richard G, Uitto J. Source: The Journal of Investigative Dermatology. 2000 February; 114(2): 381-7. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10652002&dopt=Abstract
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Epilepsy and mental retardation in a subset of early onset 4q35-facioscapulohumeral muscular dystrophy. Author(s): Funakoshi M, Goto K, Arahata K. Source: Neurology. 1998 June; 50(6): 1791-4. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=9633729&dopt=Abstract
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Epiphora as a presenting sign of facioscapulohumeral muscular dystrophy. Author(s): Funnell CL, George ND. Source: Journal of Pediatric Ophthalmology and Strabismus. 2003 March-April; 40(2): 113-4. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12691238&dopt=Abstract
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epsilon-Sarcoglycan, a broadly expressed homologue of the gene mutated in limbgirdle muscular dystrophy 2D. Author(s): Ettinger AJ, Feng G, Sanes JR. Source: The Journal of Biological Chemistry. 1997 December 19; 272(51): 32534-8. Erratum In: J Biol Chem 1998 July 31; 273(31): 19922. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=9405466&dopt=Abstract
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ERG in Duchenne/Becker muscular dystrophy. Author(s): Fitzgerald KM, Cibis GW, White RA. Source: Pediatric Neurology. 1998 November; 19(5): 400-1. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=9880152&dopt=Abstract
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ERG phenotype of a dystrophin mutation in heterozygous female carriers of Duchenne muscular dystrophy. Author(s): Fitzgerald KM, Cibis GW, Gettel AH, Rinaldi R, Harris DJ, White RA. Source: Journal of Medical Genetics. 1999 April; 36(4): 316-22. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10227401&dopt=Abstract
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Esophageal motility disorders in Mexican patients with Duchenne's muscular dystrophy. Author(s): Camelo AL, Awad RA, Madrazo A, Aguilar F, Award RA. Source: Acta Gastroenterol Latinoam. 1997; 27(3): 119-22. Erratum In: Acta Gastroenterol Latinoam 1998; 28(1): 46. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=9339236&dopt=Abstract
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Estimation of body composition in muscular dystrophy by MRI and stereology. Author(s): Gong QY, Phoenix J, Kemp GJ, Garcia-Finana M, Frostick SP, Brodie DA, Edwards RH, Whitehouse GH, Roberts N. Source: Journal of Magnetic Resonance Imaging : Jmri. 2000 September; 12(3): 467-75. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10992315&dopt=Abstract
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Evaluation of a program for long-term treatment of Duchenne muscular dystrophy. Experience at the University Hospitals of Cleveland. Author(s): Vignos PJ, Wagner MB, Karlinchak B, Katirji B. Source: The Journal of Bone and Joint Surgery. American Volume. 1996 December; 78(12): 1844-52. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=8986661&dopt=Abstract
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Evaluation of dysrhythmia in children with muscular dystrophy. Author(s): Oguz D, Olgunturk R, Tunaoglu FS, Gucuyener K, Kose G, Unlu M. Source: Angiology. 2000 November; 51(11): 925-31. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11103861&dopt=Abstract
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Evaluation of microchip electrophoresis as a molecular diagnostic method for Duchenne muscular dystrophy. Author(s): Ferrance J, Snow K, Landers JP. Source: Clinical Chemistry. 2002 February; 48(2): 380-3. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11805028&dopt=Abstract
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Evaluation of the facioscapulohumeral muscular dystrophy (FSHD1) phenotype in correlation to the concurrence of 4q35 and 10q26 fragments. Author(s): Kohler J, Rohrig D, Bathke KD, Koch MC. Source: Clinical Genetics. 1999 February; 55(2): 88-94. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10189085&dopt=Abstract
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Evidence for anticipation and association of deletion size with severity in facioscapulohumeral muscular dystrophy. The FSH-DY Group. Author(s): Tawil R, Forrester J, Griggs RC, Mendell J, Kissel J, McDermott M, King W, Weiffenbach B, Figlewicz D. Source: Annals of Neurology. 1996 June; 39(6): 744-8. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=8651646&dopt=Abstract
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Evidence for anticipation in autosomal dominant limb-girdle muscular dystrophy. Author(s): Speer MC, Gilchrist JM, Stajich JM, Gaskell PC, Westbrook CA, Horrigan SK, Bartoloni L, Yamaoka LH, Scott WK, Pericak-Vance MA. Source: Journal of Medical Genetics. 1998 April; 35(4): 305-8. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=9598725&dopt=Abstract
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Evidence of left ventricular dysfunction in children with merosin-deficient congenital muscular dystrophy. Author(s): Spyrou N, Philpot J, Foale R, Camici PG, Muntoni F. Source: American Heart Journal. 1998 September; 136(3): 474-6. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=9736139&dopt=Abstract
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Evoked potential study in facio-scapulo-humeral muscular dystrophy. Author(s): Fierro B, Daniele O, Aloisio A, Buffa D, La Bua V, Oliveri M, Manfre L, Brighina F. Source: Acta Neurologica Scandinavica. 1997 June; 95(6): 346-50. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=9228268&dopt=Abstract
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Evolution of cardiac abnormalities in Becker muscular dystrophy over a 13-year period. Author(s): Hoogerwaard EM, de Voogt WG, Wilde AA, van der Wouw PA, Bakker E, van Ommen GJ, de Visser M. Source: Journal of Neurology. 1997 October; 244(10): 657-63. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=9402544&dopt=Abstract
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Examination of telomere lengths in muscle tissue casts doubt on replicative aging as cause of progression in Duchenne muscular dystrophy. Author(s): Oexle K, Zwirner A, Freudenberg K, Kohlschutter A, Speer A. Source: Pediatric Research. 1997 August; 42(2): 226-31. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=9262227&dopt=Abstract
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Exclusion of identified LGMD1 loci from four dominant limb-girdle muscular dystrophy families. Author(s): Speer MC, Vance JM, Lennon-Graham F, Stajich JM, Viles KD, Gilchrist JM, Nigro V, McMichael R, Chutkow JG, Bartoloni L, Horrigan SK, Westbrook CA, PericakVance MA. Source: Human Heredity. 1998 July-August; 48(4): 179-84. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=9694248&dopt=Abstract
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Exclusion of muscle specific actinin-associated LIM protein (ALP) gene from 4q35 facioscapulohumeral muscular dystrophy (FSHD) candidate genes. Author(s): Bouju S, Pietu G, Le Cunff M, Cros N, Malzac P, Pellissier JF, Pons F, Leger JJ, Auffray C, Dechesne CA. Source: Neuromuscular Disorders : Nmd. 1999 January; 9(1): 3-10. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10063829&dopt=Abstract
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Expression and distribution of a small-conductance calcium-activated potassium channel (SK3) protein in skeletal muscles from myotonic muscular dystrophy patients and congenital myotonic mice. Author(s): Kimura T, Takahashi MP, Fujimura H, Sakoda S. Source: Neuroscience Letters. 2003 August 28; 347(3): 191-5. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12875918&dopt=Abstract
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Expression and localization of protein inhibitor of neuronal nitric oxide synthase in Duchenne muscular dystrophy. Author(s): Guo Y, Petrof BJ, Hussain SN. Source: Muscle & Nerve. 2001 November; 24(11): 1468-75. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11745948&dopt=Abstract
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Expression of lamin A mutated in the carboxyl-terminal tail generates an aberrant nuclear phenotype similar to that observed in cells from patients with Dunnigan-type partial lipodystrophy and Emery-Dreifuss muscular dystrophy. Author(s): Favreau C, Dubosclard E, Ostlund C, Vigouroux C, Capeau J, Wehnert M, Higuet D, Worman HJ, Courvalin JC, Buendia B. Source: Experimental Cell Research. 2003 January 1; 282(1): 14-23. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12490190&dopt=Abstract
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Expression of laminin chains in skin in merosin-deficient congenital muscular dystrophy. Author(s): Sewry CA, D'Alessandro M, Wilson LA, Sorokin LM, Naom I, Bruno S, Ferlini A, Dubowitz V, Muntoni F. Source: Neuropediatrics. 1997 August; 28(4): 217-22. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=9309712&dopt=Abstract
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Expression of plectin and HD1 epitopes in patients with epidermolysis bullosa simplex associated with muscular dystrophy. Author(s): Shimizu H, Masunaga T, Kurihara Y, Owaribe K, Wiche G, Pulkkinen L, Uitto J, Nishikawa T. Source: Archives of Dermatological Research. 1999 October; 291(10): 531-7. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10552210&dopt=Abstract
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Extraosseous uptake of Tc-99m HDP in muscular dystrophy. Author(s): Nye PJ, Aelion JA, Odhav SK, Bain S. Source: Clinical Nuclear Medicine. 2000 February; 25(2): 135-6. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10656652&dopt=Abstract
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Facial structure and functional findings in patients with progressive muscular dystrophy (Duchenne). Author(s): Eckardt L, Harzer W. Source: American Journal of Orthodontics and Dentofacial Orthopedics : Official Publication of the American Association of Orthodontists, Its Constituent Societies, and the American Board of Orthodontics. 1996 August; 110(2): 185-90. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=8760845&dopt=Abstract
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Facioscapulohumeral (FSHD1) and other forms of muscular dystrophy in the same family: is there more in muscular dystrophy than meets the eye? Author(s): Tonini MM, Passos-Bueno MR, Cerqueira A, Pavanello R, Vainzof M, Dubowitz V, Zatz M. Source: Neuromuscular Disorders : Nmd. 2002 August; 12(6): 554-7. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12117479&dopt=Abstract
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Facioscapulohumeral muscular dystrophy (FSHD) myoblasts demonstrate increased susceptibility to oxidative stress. Author(s): Winokur ST, Barrett K, Martin JH, Forrester JR, Simon M, Tawil R, Chung SA, Masny PS, Figlewicz DA. Source: Neuromuscular Disorders : Nmd. 2003 May; 13(4): 322-33. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12868502&dopt=Abstract
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Facioscapulohumeral muscular dystrophy (FSHD): design of natural history study and results of baseline testing. FSH-DY Group. Author(s): Tawil R, McDermott MP, Mendell JR, Kissel J, Griggs RC. Source: Neurology. 1994 March; 44(3 Pt 1): 442-6. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=8145913&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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Facioscapulohumeral muscular dystrophy in early childhood. Author(s): Brouwer OF, Padberg GW, Wijmenga C, Frants RR. Source: Archives of Neurology. 1994 April; 51(4): 387-94. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=8155016&dopt=Abstract
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Facioscapulohumeral muscular dystrophy in the Dutch population. Author(s): Padberg GW, Frants RR, Brouwer OF, Wijmenga C, Bakker E, Sandkuijl LA. Source: Muscle & Nerve. 1995; 2: S81-4. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=7739631&dopt=Abstract
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Facioscapulohumeral muscular dystrophy is uniquely associated with one of the two variants of the 4q subtelomere. Author(s): Lemmers RJ, de Kievit P, Sandkuijl L, Padberg GW, van Ommen GJ, Frants RR, van der Maarel SM. Source: Nature Genetics. 2002 October; 32(2): 235-6. Epub 2002 September 23. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12355084&dopt=Abstract
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Facioscapulohumeral muscular dystrophy presenting isolated monomelic lower limb atrophy. Report of two patients with and without 4q35 rearrangement. Author(s): Uncini A, Galluzzi G, Di Muzio A, De Angelis MV, Ricci E, Scoppetta C, Servidei S. Source: Neuromuscular Disorders : Nmd. 2002 November; 12(9): 874-7. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12398841&dopt=Abstract
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Facioscapulohumeral muscular dystrophy with chromosome 9p deletion. Author(s): Ueyama H, Kumamoto T, Mita S, Kimura E, Nakagawa M, Uchino M, Ando M. Source: Neurology. 1996 February; 46(2): 566-9. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=8614537&dopt=Abstract
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Facioscapulohumeral muscular dystrophy with EcoRI/BlnI fragment size of more than 32 kb. Author(s): Vielhaber S, Jakubiczka S, Schroder JM, Sailer M, Feistner H, Heinze HJ, Wieacker P, Bettecken T. Source: Muscle & Nerve. 2002 April; 25(4): 540-8. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11932972&dopt=Abstract
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Facioscapulohumeral muscular dystrophy. Author(s): Fitzsimons RB. Source: Current Opinion in Neurology. 1999 October; 12(5): 501-11. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10590886&dopt=Abstract
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Facioscapulohumeral muscular dystrophy: clinical diversity and genetic abnormalities in Japanese patients. Author(s): Nakagawa M, Matsuzaki T, Higuchi I, Fukunaga H, Inui T, Nagamitsu S, Yamada H, Arimura K, Osame M. Source: Intern Med. 1997 May; 36(5): 333-9. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=9213170&dopt=Abstract
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Failure of early diagnosis in symptomatic Duchenne muscular dystrophy. Author(s): Bushby KM, Hill A, Steele JG. Source: Lancet. 1999 February 13; 353(9152): 557-8. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10028989&dopt=Abstract
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Familial arachnoid cysts associated with oculopharyngeal muscular dystrophy. Author(s): Jadeja KJ, Grewal RP. Source: Journal of Clinical Neuroscience : Official Journal of the Neurosurgical Society of Australasia. 2003 January; 10(1): 125-7. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12464544&dopt=Abstract
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Familial concordance of brain magnetic resonance imaging changes in congenital muscular dystrophy. Author(s): Philpot J, Topaloglu H, Pennock J, Dubowitz V. Source: Neuromuscular Disorders : Nmd. 1995 May; 5(3): 227-31. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=7633188&dopt=Abstract
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Familial facioscapulohumeral muscular dystrophy: phenotypic diversity and genetic abnormality. Author(s): Nakagawa M, Higuchi I, Yoshidome H, Isashiki Y, Ohkubo R, Kaseda S, Iwaki H, Fukunaga H, Osame M. Source: Acta Neurologica Scandinavica. 1996 February-March; 93(2-3): 189-92. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=8741141&dopt=Abstract
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Feeding problems in merosin deficient congenital muscular dystrophy. Author(s): Philpot J, Bagnall A, King C, Dubowitz V, Muntoni F. Source: Archives of Disease in Childhood. 1999 June; 80(6): 542-7. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10332004&dopt=Abstract
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Fetal muscle biopsy as a diagnostic tool in Duchenne muscular dystrophy. Author(s): Nevo Y, Shomrat R, Yaron Y, Orr-Urtreger A, Harel S, Legum C. Source: Prenatal Diagnosis. 1999 October; 19(10): 921-6. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10521816&dopt=Abstract
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First meeting of the Duchenne Parent Project in Europe: Treatment of Duchenne Muscular Dystrophy. 7-8 November 1997, Rotterdam, The Netherlands. Author(s): Scheuerbrandt G. Source: Neuromuscular Disorders : Nmd. 1998 May; 8(3-4): 213-9. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=9631405&dopt=Abstract
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Founder-haplotype analysis in Fukuyama-type congenital muscular dystrophy (FCMD). Author(s): Kobayashi K, Nakahori Y, Mizuno K, Miyake M, Kumagai T, Honma A, Nonaka I, Nakamura Y, Tokunaga K, Toda T. Source: Human Genetics. 1998 September; 103(3): 323-7. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=9799088&dopt=Abstract
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Four novel dystrophin point mutations: detection by protein truncation test and transcript analysis in lymphocytes from Duchenne muscular dystrophy patients. Author(s): Tuffery S, Bareil C, Demaille J, Claustres M. Source: European Journal of Human Genetics : Ejhg. 1996; 4(3): 143-52. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=8840114&dopt=Abstract
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Four novel plectin gene mutations in Japanese patients with epidermolysis bullosa with muscular dystrophy disclosed by heteroduplex scanning and protein truncation tests. Author(s): Takizawa Y, Shimizu H, Rouan F, Kawai M, Udono M, Pulkkinen L, Nishikawa T, Uitto J. Source: The Journal of Investigative Dermatology. 1999 January; 112(1): 109-12. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=9886273&dopt=Abstract
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Fracture prevalence in Duchenne muscular dystrophy. Author(s): McDonald DG, Kinali M, Gallagher AC, Mercuri E, Muntoni F, Roper H, Jardine P, Jones DH, Pike MG. Source: Developmental Medicine and Child Neurology. 2002 October; 44(10): 695-8. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12418795&dopt=Abstract
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Fracture risk in patients with muscular dystrophy and spinal muscular atrophy. Author(s): Vestergaard P, Glerup H, Steffensen BF, Rejnmark L, Rahbek J, Moseklide L. Source: Journal of Rehabilitation Medicine : Official Journal of the Uems European Board of Physical and Rehabilitation Medicine. 2001 July; 33(4): 150-5. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11506212&dopt=Abstract
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Frameshift deletions of exons 3-7 and revertant fibers in Duchenne muscular dystrophy: mechanisms of dystrophin production. Author(s): Winnard AV, Mendell JR, Prior TW, Florence J, Burghes AH. Source: American Journal of Human Genetics. 1995 January; 56(1): 158-66. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=7825572&dopt=Abstract
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Free radicals, programmed cell death and muscular dystrophy. Author(s): Brown RH. Source: Current Opinion in Neurology. 1995 October; 8(5): 373-8. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=8542043&dopt=Abstract
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Freeze-fracture analysis of muscle plasma membrane in Becker's muscular dystrophy. Author(s): Shibuya S, Wakayama Y, Jimi T, Oniki H, Kobayashi T, Misugi N, Kumagai T, Hasegawa O, Suzuki Y, Kuroiwa Y. Source: Neuropathology and Applied Neurobiology. 1994 October; 20(5): 487-94. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=7845534&dopt=Abstract
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Frequent low penetrance mutations in the Lamin A/C gene, causing Emery Dreifuss muscular dystrophy. Author(s): Vytopil M, Ricci E, Dello Russo A, Hanisch F, Neudecker S, Zierz S, Ricotti R, Demay L, Richard P, Wehnert M, Bonne G, Merlini L, Toniolo D. Source: Neuromuscular Disorders : Nmd. 2002 December; 12(10): 958-63. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12467752&dopt=Abstract
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FRG1, a gene in the FSH muscular dystrophy region on human chromosome 4q35, is highly conserved in vertebrates and invertebrates. Author(s): Grewal PK, Todd LC, van der Maarel S, Frants RR, Hewitt JE. Source: Gene. 1998 August 17; 216(1): 13-9. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=9714712&dopt=Abstract
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From dystrophinopathy to sarcoglycanopathy: evolution of a concept of muscular dystrophy. Author(s): Ozawa E, Noguchi S, Mizuno Y, Hagiwara Y, Yoshida M. Source: Muscle & Nerve. 1998 April; 21(4): 421-38. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=9533777&dopt=Abstract
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Fukutin expression in glial cells and neurons: implication in the brain lesions of Fukuyama congenital muscular dystrophy. Author(s): Yamamoto T, Kato Y, Karita M, Takeiri H, Muramatsu F, Kobayashi M, Saito K, Osawa M. Source: Acta Neuropathologica. 2002 September; 104(3): 217-24. Epub 2002 June 21. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12172906&dopt=Abstract
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Fukutin protein is expressed in neurons of the normal developing human brain but is reduced in Fukuyama-type congenital muscular dystrophy brain. Author(s): Saito Y, Mizuguchi M, Oka A, Takashima S. Source: Annals of Neurology. 2000 June; 47(6): 756-64. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10852541&dopt=Abstract
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Fukuyama congenital muscular dystrophy: a neuroradiologic review. Author(s): Aida N. Source: Journal of Magnetic Resonance Imaging : Jmri. 1998 March-April; 8(2): 317-26. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=9562058&dopt=Abstract
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Fukuyama muscular dystrophy associated with lack of C-terminal domain of dystrophin. Author(s): Tachi N, Chiba S, Matsuo M, Matsumura K, Saito K. Source: Pediatric Neurology. 2001 May; 24(5): 373-8. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11516613&dopt=Abstract
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Fukuyama-type congenital muscular dystrophy: a case report in the Japanese population living in Brazil. Author(s): Zanoteli E, Rocha JC, Narumia LK, Fireman MA, Moura LS, Oliveira AS, Gabbai AA, Fukuda Y, Kinoshita M, Toda T. Source: Acta Neurologica Scandinavica. 2002 August; 106(2): 117-21. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12100373&dopt=Abstract
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Fukuyama-type congenital muscular dystrophy: close relation between changes in the muscle basal lamina and plasma membrane. Author(s): Matsubara S, Mizuno Y, Kitaguchi T, Isozaki E, Miyamoto K, Hirai S. Source: Neuromuscular Disorders : Nmd. 1999 October; 9(6-7): 388-98. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10545042&dopt=Abstract
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Fukuyama-type congenital muscular dystrophy: the first human disease to be caused by an ancient retrotransposal integration. Author(s): Toda T, Kobayashi K. Source: Journal of Molecular Medicine (Berlin, Germany). 1999 December; 77(12): 816-23. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10682317&dopt=Abstract
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Functional defects of a muscle-specific calpain, p94, caused by mutations associated with limb-girdle muscular dystrophy type 2A. Author(s): Ono Y, Shimada H, Sorimachi H, Richard I, Saido TC, Beckmann JS, Ishiura S, Suzuki K. Source: The Journal of Biological Chemistry. 1998 July 3; 273(27): 17073-8. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=9642272&dopt=Abstract
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Functional domains of the nucleus: implications for Emery-Dreifuss muscular dystrophy. Author(s): Maraldi NM, Lattanzi G, Sabatelli P, Ognibene A, Squarzoni S. Source: Neuromuscular Disorders : Nmd. 2002 November; 12(9): 815-23. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12398831&dopt=Abstract
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Functional involvement of cerebral cortex in Duchenne muscular dystrophy. Author(s): Di Lazzaro V, Restuccia D, Servidei S, Nardone R, Oliviero A, Profice P, Mangiola F, Tonali P, Rothwell JC. Source: Muscle & Nerve. 1998 May; 21(5): 662-4. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=9572251&dopt=Abstract
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Functional muscle ischemia in neuronal nitric oxide synthase-deficient skeletal muscle of children with Duchenne muscular dystrophy. Author(s): Sander M, Chavoshan B, Harris SA, Iannaccone ST, Stull JT, Thomas GD, Victor RG. Source: Proceedings of the National Academy of Sciences of the United States of America. 2000 December 5; 97(25): 13818-23. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11087833&dopt=Abstract
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Functional significance of dystrophin-positive fibers in Duchenne and Becker muscular dystrophy. Author(s): Tasdemir HA, Kotiloglu E, Topaloglu H, Kale G, Dincer DP, Yalaz K, Renda Y. Source: Pediatric Pathology & Laboratory Medicine : Journal of the Society for Pediatric Pathology, Affiliated with the International Paediatric Pathology Association. 1996 JulyAugust; 16(4): 583-90. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=9025855&dopt=Abstract
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gamma-sarcoglycan deficiency muscular dystrophy in two adults. Author(s): Lin KL, Wang HS, Chen ST, Ro LS. Source: J Formos Med Assoc. 2000 October; 99(10): 789-91. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11061077&dopt=Abstract
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Gastric emptying time in children with progressive muscular dystrophy. Author(s): Okan M, Alper E, Cil E, Eralp O, Agir H. Source: Turk J Pediatr. 1997 January-March; 39(1): 69-74. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10868196&dopt=Abstract
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Gastric wall weakening resulting in separate perforations in a patient with Duchenne's muscular dystrophy. Author(s): Dinan D, Levine MS, Gordon AR, Rubesin SE, Rombeau JL. Source: Ajr. American Journal of Roentgenology. 2003 September; 181(3): 807-8. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12933486&dopt=Abstract
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Gastroparesis associated with muscular dystrophy. Author(s): Rohira SK, Bianco JA. Source: Clinical Nuclear Medicine. 1993 November; 18(11): 996. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=8269689&dopt=Abstract
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GCG genetic expansions in Italian patients with oculopharyngeal muscular dystrophy. Author(s): Mirabella M, Silvestri G, de Rosa G, Di Giovanni S, Di Muzio A, Uncini A, Tonali P, Servidei S. Source: Neurology. 2000 February 8; 54(3): 608-14. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10680791&dopt=Abstract
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GCG repeats and phenotype in oculopharyngeal muscular dystrophy. Author(s): Muller T, Schroder R, Zierz S. Source: Muscle & Nerve. 2001 January; 24(1): 120-2. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11150975&dopt=Abstract
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Gene deletion and carrier detection in the family of Becker muscular dystrophy by short tandem repeat sequence polymorphism. Author(s): Cai S, Shen D, Wang J. Source: Chin Med J (Engl). 1999 March; 112(3): 242-5. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11593558&dopt=Abstract
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Gene expression comparison of biopsies from Duchenne muscular dystrophy (DMD) and normal skeletal muscle. Author(s): Haslett JN, Sanoudou D, Kho AT, Bennett RR, Greenberg SA, Kohane IS, Beggs AH, Kunkel LM. Source: Proceedings of the National Academy of Sciences of the United States of America. 2002 November 12; 99(23): 15000-5. Epub 2002 Nov 01. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12415109&dopt=Abstract
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Gene removes muscular dystrophy symptoms in mouse model. Author(s): Senior K. Source: Lancet. 2001 September 22; 358(9286): 990. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11583760&dopt=Abstract
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Gene therapy in Duchenne muscular dystrophy. Author(s): Inui K, Okada S, Dickson G. Source: Brain & Development. 1996 September-October; 18(5): 357-61. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=8891229&dopt=Abstract
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Gene therapy of Duchenne muscular dystrophy. Author(s): Fassati A, Murphy S, Dickson G. Source: Adv Genet. 1997; 35: 117-53. Review. No Abstract Available. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=9348647&dopt=Abstract
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Gene therapy of muscular dystrophy. Author(s): Chamberlain JS. Source: Human Molecular Genetics. 2002 October 1; 11(20): 2355-62. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12351570&dopt=Abstract
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Gene therapy prospects for Duchenne muscular dystrophy. Author(s): Clemens PR, Caskey CT. Source: European Neurology. 1994; 34(4): 181-5. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=8082675&dopt=Abstract
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Genealogical study of oculopharyngeal muscular dystrophy in France. Author(s): Brunet G, Tome FM, Eymard B, Robert JM, Fardeau M. Source: Neuromuscular Disorders : Nmd. 1997 October; 7 Suppl 1: S34-7. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=9392013&dopt=Abstract
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Generation of a 3-Mb PAC contig spanning the Miyoshi myopathy/limb-girdle muscular dystrophy (MM/LGMD2B) locus on chromosome 2p13. Author(s): Liu J, Wu C, Bossie K, Bejaoui K, Hosler BA, Gingrich JC, Ben Hamida M, Hentati F, Schurr E, de Jong PJ, Brown RH Jr. Source: Genomics. 1998 April 1; 49(1): 23-9. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=9570945&dopt=Abstract
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Genetic and biochemical normalization in female carriers of Duchenne muscular dystrophy: evidence for failure of dystrophin production in dystrophin-competent myonuclei. Author(s): Pegoraro E, Schimke RN, Garcia C, Stern H, Cadaldini M, Angelini C, Barbosa E, Carroll J, Marks WA, Neville HE. Source: Neurology. 1995 April; 45(4): 677-90. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=7723955&dopt=Abstract
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Genetic and physical mapping at the limb-girdle muscular dystrophy locus (LGMD2B) on chromosome 2p. Author(s): Bashir R, Keers S, Strachan T, Passos-Bueno R, Zatz M, Weissenbach J, Le Paslier D, Meisler M, Bushby K. Source: Genomics. 1996 April 1; 33(1): 46-52. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=8617508&dopt=Abstract
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Genetic counseling for childless women at risk for Duchenne muscular dystrophy. Author(s): Eggers S, Pavanello RC, Passos-Bueno MR, Zatz M. Source: American Journal of Medical Genetics. 1999 October 29; 86(5): 447-53. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10508987&dopt=Abstract
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Genetic counseling of isolated carriers of Duchenne muscular dystrophy. Author(s): Hoffman EP, Pegoraro E, Scacheri P, Burns RG, Taber JW, Weiss L, Spiro A, Blattner P. Source: American Journal of Medical Genetics. 1996 June 28; 63(4): 573-80. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=8826437&dopt=Abstract
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Genetic epidemiology of congenital muscular dystrophy in a sample from north-east Italy. Author(s): Mostacciuolo ML, Miorin M, Martinello F, Angelini C, Perini P, Trevisan CP. Source: Human Genetics. 1996 March; 97(3): 277-9. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=8786062&dopt=Abstract
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Genetic epidemiology of Duchenne and Becker muscular dystrophy in Slovenia. Author(s): Peterlin B, Zidar J, Meznaric-Petrusa M, Zupancic N. Source: Clinical Genetics. 1997 February; 51(2): 94-7. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=9111995&dopt=Abstract
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Genetic heterogeneity for Duchenne-like muscular dystrophy (DLMD) based on linkage and 50 DAG analysis. Author(s): Passos-Bueno MR, Oliveira JR, Bakker E, Anderson RD, Marie SK, Vainzof M, Roberds S, Campbell KP, Zatz M. Source: Human Molecular Genetics. 1993 November; 2(11): 1945-7. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=8281158&dopt=Abstract
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Genetic heterogeneity in Miyoshi-type distal muscular dystrophy. Author(s): Linssen WH, de Visser M, Notermans NC, Vreyling JP, Van Doorn PA, Wokke JH, Baas F, Bolhuis PA. Source: Neuromuscular Disorders : Nmd. 1998 June; 8(5): 317-20. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=9673985&dopt=Abstract
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Genetic heterogeneity in three Chinese children with Fukuyama congenital muscular dystrophy. Author(s): Jong YJ, Kobayashi K, Toda T, Kondo E, Huang SC, Shen YZ, Nonaka I, Fukuyama Y. Source: Neuromuscular Disorders : Nmd. 2000 February; 10(2): 108-12. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10714585&dopt=Abstract
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Genetic heterogeneity of autosomal recessive limb-girdle muscular dystrophy in a genetic isolate (Amish) and evidence for a new locus. Author(s): Allamand V, Broux O, Bourg N, Richard I, Tischfield JA, Hodes ME, Conneally PM, Fardeau M, Jackson CE, Beckmann JS. Source: Human Molecular Genetics. 1995 March; 4(3): 459-63. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=7795603&dopt=Abstract
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Genetic heterogeneity of congenital muscular dystrophy with rigid spine syndrome. Author(s): Moghadaszadeh B, Topaloglu H, Merlini L, Muntoni F, Estournet B, Sewry C, Naom I, Barois A, Fardeau M, Tome FM, Guicheney P. Source: Neuromuscular Disorders : Nmd. 1999 October; 9(6-7): 376-82. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10545040&dopt=Abstract
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Genetic heterogeneity of severe childhood autosomal recessive muscular dystrophy with adhalin (50 kDa dystrophin-associated glycoprotein) deficiency. Author(s): Romero NB, Tome FM, Leturcq F, el Kerch FE, Azibi K, Bachner L, Anderson RD, Roberds SL, Campbell KP, Fardeau M, et al. Source: Comptes Rendus De L'academie Des Sciences. Serie Iii, Sciences De La Vie. 1994 January; 317(1): 70-6. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=7987694&dopt=Abstract
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Genetic identity of Fukuyama-type congenital muscular dystrophy and WalkerWarburg syndrome. Author(s): Toda T, Yoshioka M, Nakahori Y, Kanazawa I, Nakamura Y, Nakagome Y. Source: Annals of Neurology. 1995 January; 37(1): 99-101. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=7818265&dopt=Abstract
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Genetic localization of a newly recognized autosomal dominant limb-girdle muscular dystrophy with cardiac involvement (LGMD1B) to chromosome 1q11-21. Author(s): van der Kooi AJ, van Meegen M, Ledderhof TM, McNally EM, de Visser M, Bolhuis PA. Source: American Journal of Human Genetics. 1997 April; 60(4): 891-5. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=9106535&dopt=Abstract
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Genetic mapping and haplotype analysis of oculopharyngeal muscular dystrophy. Author(s): Grewal RP, Cantor R, Turner G, Grewal RK, Detera-Wadleigh SD. Source: Neuroreport. 1998 April 20; 9(6): 961-5. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=9601650&dopt=Abstract
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Genetic polymorphism in muscle biopsies of Duchenne and Becker muscular dystrophy patients. Author(s): Anand A, Prabhakar S, Kaul D. Source: Neurology India. 1999 September; 47(3): 218-23. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10514583&dopt=Abstract
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Genetics of facioscapulohumeral muscular dystrophy: new mutations in sporadic cases. Author(s): Griggs RC, Tawil R, Storvick D, Mendell JR, Altherr MR. Source: Neurology. 1993 November; 43(11): 2369-72. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=8232958&dopt=Abstract
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Genetics of laminin alpha 2 chain (or merosin) deficient congenital muscular dystrophy: from identification of mutations to prenatal diagnosis. Author(s): Guicheney P, Vignier N, Helbling-Leclerc A, Nissinen M, Zhang X, Cruaud C, Lambert JC, Richelme C, Topaloglu H, Merlini L, Barois A, Schwartz K, Tome FM, Tryggvason K, Fardeau M. Source: Neuromuscular Disorders : Nmd. 1997 May; 7(3): 180-6. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=9185182&dopt=Abstract
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Genomic screening for beta-sarcoglycan gene mutations: missense mutations may cause severe limb-girdle muscular dystrophy type 2E (LGMD 2E). Author(s): Bonnemann CG, Passos-Bueno MR, McNally EM, Vainzof M, de Sa Moreira E, Marie SK, Pavanello RC, Noguchi S, Ozawa E, Zatz M, Kunkel LM. Source: Human Molecular Genetics. 1996 December; 5(12): 1953-61. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=8968749&dopt=Abstract
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Genotype and electroretinal heterogeneity in Duchenne muscular dystrophy. Author(s): Ino-ue M, Honda S, Nishio H, Matsuo M, Nakamura H, Yamamoto M. Source: Experimental Eye Research. 1997 December; 65(6): 861-4. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=9441711&dopt=Abstract
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Genotype-phenotype analysis in X-linked Emery-Dreifuss muscular dystrophy and identification of a missense mutation associated with a milder phenotype. Author(s): Yates JR, Bagshaw J, Aksmanovic VM, Coomber E, McMahon R, Whittaker JL, Morrison PJ, Kendrick-Jones J, Ellis JA. Source: Neuromuscular Disorders : Nmd. 1999 May; 9(3): 159-65. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10382909&dopt=Abstract
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Genotype-phenotype correlation in Duchenne/Becker muscular dystrophy patients seen at Lucknow. Author(s): Mittal B, Singh V, Mishra S, Sinha S, Mittal RD, Chaturvedi LS, Danda S, Pradhan S, Agarwal SS. Source: The Indian Journal of Medical Research. 1997 January; 105: 32-8. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=9029833&dopt=Abstract
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Gentamicin treatment of Duchenne and Becker muscular dystrophy due to nonsense mutations. Author(s): Wagner KR, Hamed S, Hadley DW, Gropman AL, Burstein AH, Escolar DM, Hoffman EP, Fischbeck KH. Source: Annals of Neurology. 2001 June; 49(6): 706-11. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11409421&dopt=Abstract
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Germinal mosaicism in facioscapulohumeral muscular dystrophy (FSHD). Author(s): Upadhyaya M, Maynard J, Osborn M, Jardine P, Harper PS, Lunt P. Source: Muscle & Nerve. 1995; 2: S45-9. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=7739625&dopt=Abstract
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Germline and somatic mosaicism in a female carrier of Duchenne muscular dystrophy. Author(s): Bunyan DJ, Robinson DO, Collins AL, Cockwell AE, Bullman HM, Whittaker PA. Source: Human Genetics. 1994 May; 93(5): 541-4. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=8168831&dopt=Abstract
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Germline mosaicism in 4q35 facioscapulohumeral muscular dystrophy (FSHD1A) occurring predominantly in oogenesis. Author(s): Kohler J, Rupilius B, Otto M, Bathke K, Koch MC. Source: Human Genetics. 1996 October; 98(4): 485-90. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=8792827&dopt=Abstract
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Giant dystrophin deletion associated with congenital cataract and mild muscular dystrophy. Author(s): Mirabella M, Galluzzi G, Manfredi G, Bertini E, Ricci E, De Leo R, Tonali P, Servidei S. Source: Neurology. 1998 August; 51(2): 592-5. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=9710043&dopt=Abstract
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Gradual onset of dysphagia: a study of patients with oculopharyngeal muscular dystrophy. Author(s): Young EC, Durant-Jones L. Source: Dysphagia. 1997 Fall; 12(4): 196-201. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=9294939&dopt=Abstract
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Haplotype-phenotype correlation in Fukuyama congenital muscular dystrophy. Author(s): Saito K, Osawa M, Wang ZP, Ikeya K, Fukuyama Y, Kondo-Iida E, Toda T, Ohashi H, Kurosawa K, Wakai S, Kaneko K. Source: American Journal of Medical Genetics. 2000 May 29; 92(3): 184-90. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10817652&dopt=Abstract
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Harnessing the potential of dystrophin-related proteins for ameliorating Duchenne's muscular dystrophy. Author(s): Krag TO, Gyrd-Hansen M, Khurana TS. Source: Acta Physiologica Scandinavica. 2001 March; 171(3): 349-58. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11412148&dopt=Abstract
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Heart to heart: from nuclear proteins to Emery-Dreifuss muscular dystrophy. Author(s): Morris GE, Manilal S. Source: Human Molecular Genetics. 1999; 8(10): 1847-51. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10469836&dopt=Abstract
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Heart-specific localization of emerin: new insights into Emery-Dreifuss muscular dystrophy. Author(s): Cartegni L, di Barletta MR, Barresi R, Squarzoni S, Sabatelli P, Maraldi N, Mora M, Di Blasi C, Cornelio F, Merlini L, Villa A, Cobianchi F, Toniolo D. Source: Human Molecular Genetics. 1997 December; 6(13): 2257-64. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=9361031&dopt=Abstract
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Hemolytic anemia associated with myotonic muscular dystrophy. Author(s): Komeno T, Ninomiya H, Itoh T, Fujita T, Nagasawa T, Abe T. Source: Intern Med. 1996 September; 35(9): 746-8. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=8915705&dopt=Abstract
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Hereditary ptosis of late onset: early observations on oculopharyngeal muscular dystrophy in Quebec by Roma Amyot. Author(s): Duquette P, Giard N. Source: Neuromuscular Disorders : Nmd. 1997 October; 7 Suppl 1: S12-4. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=9392009&dopt=Abstract
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Heterogeneity in familial dominant Paget disease of bone and muscular dystrophy. Author(s): Waggoner B, Kovach MJ, Winkelman M, Cai D, Khardori R, Gelber D, Kimonis VE. Source: American Journal of Medical Genetics. 2002 March 15; 108(3): 187-91. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11891683&dopt=Abstract
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Heterogeneity of classic congenital muscular dystrophy with involvement of the central nervous system: report of five atypical cases. Author(s): Reed UC, Marie SK, Vainzof M, Gobbo LF, Gurgel JE, Carvalho MS, Resende MB, Espindola AA, Zatz M, Diament A. Source: Journal of Child Neurology. 2000 March; 15(3): 172-8. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10757473&dopt=Abstract
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Heterozygous myogenic factor 6 mutation associated with myopathy and severe course of Becker muscular dystrophy. Author(s): Kerst B, Mennerich D, Schuelke M, Stoltenburg-Didinger G, von Moers A, Gossrau R, van Landeghem FK, Speer A, Braun T, Hubner C. Source: Neuromuscular Disorders : Nmd. 2000 December; 10(8): 572-7. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11053684&dopt=Abstract
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High dose weekly oral prednisone improves strength in boys with Duchenne muscular dystrophy. Author(s): Connolly AM, Schierbecker J, Renna R, Florence J. Source: Neuromuscular Disorders : Nmd. 2002 December; 12(10): 917-25. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12467746&dopt=Abstract
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High frequency of de novo deletions in Mexican Duchenne and Becker muscular dystrophy patients. Implications for genetic counseling. Author(s): Alcantara MA, Villarreal MT, Del Castillo V, Gutierrez G, Saldana Y, Maulen I, Lee R, Macias M, Orozco L. Source: Clinical Genetics. 1999 May; 55(5): 376-80. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10422811&dopt=Abstract
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High frequency of new mutations in North Indian Duchenne/Becker muscular dystrophy patients. Author(s): Sinha S, Mishra S, Singh V, Mittal RD, Mittal B. Source: Clinical Genetics. 1996 November; 50(5): 327-31. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=9007319&dopt=Abstract
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High proportion of new mutations and possible anticipation in Brazilian facioscapulohumeral muscular dystrophy families. Author(s): Zatz M, Marie SK, Passos-Bueno MR, Vainzof M, Campiotto S, Cerqueira A, Wijmenga C, Padberg G, Frants R. Source: American Journal of Human Genetics. 1995 January; 56(1): 99-105. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=7825608&dopt=Abstract
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High resolution fluorescence in situ hybridization to linearly extended DNA visually maps a tandem repeat associated with facioscapulohumeral muscular dystrophy immediately adjacent to the telomere of 4q. Author(s): Bengtsson U, Altherr MR, Wasmuth JJ, Winokur ST. Source: Human Molecular Genetics. 1994 October; 3(10): 1801-5. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=7849703&dopt=Abstract
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High resolution magnetic resonance imaging of the brain in the dy/dy mouse with merosin-deficient congenital muscular dystrophy. Author(s): Dubowitz DJ, Tyszka JM, Sewry CA, Moats RA, Scadeng M, Dubowitz V. Source: Neuromuscular Disorders : Nmd. 2000 June; 10(4-5): 292-8. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10838257&dopt=Abstract
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Hip subluxation and dislocation in Duchenne muscular dystrophy. Author(s): Chan KG, Galasko CS, Delaney C. Source: Journal of Pediatric Orthopaedics. Part B / European Paediatric Orthopaedic Society, Pediatric Orthopaedic Society of North America. 2001 July; 10(3): 219-25. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11497366&dopt=Abstract
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HnRNP A1 and A/B interaction with PABPN1 in oculopharyngeal muscular dystrophy. Author(s): Fan X, Messaed C, Dion P, Laganiere J, Brais B, Karpati G, Rouleau GA. Source: The Canadian Journal of Neurological Sciences. Le Journal Canadien Des Sciences Neurologiques. 2003 August; 30(3): 244-51. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12945950&dopt=Abstract
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Homozygotes for oculopharyngeal muscular dystrophy have a severe form of the disease. Author(s): Blumen SC, Brais B, Korczyn AD, Medinsky S, Chapman J, Asherov A, Nisipeanu P, Codere F, Bouchard JP, Fardeau M, Tome FM, Rouleau GA. Source: Annals of Neurology. 1999 July; 46(1): 115-8. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10401788&dopt=Abstract
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Homozygous alpha-sarcoglycan mutation in two siblings: one asymptomatic and one steroid-responsive mild limb-girdle muscular dystrophy patient. Author(s): Angelini C, Fanin M, Menegazzo E, Freda MP, Duggan DJ, Hoffman EP. Source: Muscle & Nerve. 1998 June; 21(6): 769-75. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=9585331&dopt=Abstract
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Homozygous deletion mutations in the plectin gene (PLEC1) in patients with epidermolysis bullosa simplex associated with late-onset muscular dystrophy. Author(s): Pulkkinen L, Smith FJ, Shimizu H, Murata S, Yaoita H, Hachisuka H, Nishikawa T, McLean WH, Uitto J. Source: Human Molecular Genetics. 1996 October; 5(10): 1539-46. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=8894687&dopt=Abstract
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How the magnitude of clinical severity and recurrence risk affects reproductive decisions in adult males with different forms of progressive muscular dystrophy. Author(s): Eggers S, Zatz M. Source: Journal of Medical Genetics. 1998 March; 35(3): 189-95. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=9541101&dopt=Abstract
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Human epsilon-sarcoglycan is highly related to alpha-sarcoglycan (adhalin), the limb girdle muscular dystrophy 2D gene. Author(s): McNally EM, Ly CT, Kunkel LM. Source: Febs Letters. 1998 January 23; 422(1): 27-32. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=9475163&dopt=Abstract
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Hyperkalaemic cardiac arrest in a manifesting carrier of Duchenne muscular dystrophy following general anaesthesia. Author(s): Kerr TP, Duward A, Hodgson SV, Hughes E, Robb SA. Source: European Journal of Pediatrics. 2001 September; 160(9): 579-80. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11585084&dopt=Abstract
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Hyperkalaemic cardiac arrest. Patient may have had a muscular dystrophy or Andersen's syndrome. Author(s): Jardine P. Source: Bmj (Clinical Research Ed.). 1996 September 14; 313(7058): 692-3. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=8811785&dopt=Abstract
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Hypoosmotic shocks induce elevation of resting calcium level in Duchenne muscular dystrophy myotubes contracting in vitro. Author(s): Imbert N, Vandebrouck C, Constantin B, Duport G, Guillou C, Cognard C, Raymond G. Source: Neuromuscular Disorders : Nmd. 1996 October; 6(5): 351-60. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=8938699&dopt=Abstract
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Identical de novo mutation at the D4F104S1 locus in monozygotic male twins affected by facioscapulohumeral muscular dystrophy (FSHD) with different clinical expression. Author(s): Tupler R, Barbierato L, Memmi M, Sewry CA, De Grandis D, Maraschio P, Tiepolo L, Ferlini A. Source: Journal of Medical Genetics. 1998 September; 35(9): 778-83. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=9733041&dopt=Abstract
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Identical dysferlin mutation in limb-girdle muscular dystrophy type 2B and distal myopathy. Author(s): Illarioshkin SN, Ivanova-Smolenskaya IA, Greenberg CR, Nylen E, Sukhorukov VS, Poleshchuk VV, Markova ED, Wrogemann K. Source: Neurology. 2000 December 26; 55(12): 1931-3. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11134403&dopt=Abstract
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Identical mutation in patients with limb girdle muscular dystrophy type 2B or Miyoshi myopathy suggests a role for modifier gene(s). Author(s): Weiler T, Bashir R, Anderson LV, Davison K, Moss JA, Britton S, Nylen E, Keers S, Vafiadaki E, Greenberg CR, Bushby CR, Wrogemann K. Source: Human Molecular Genetics. 1999 May; 8(5): 871-7. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10196377&dopt=Abstract
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Identification and quantification of somatic mosaicism for a point mutation in a Duchenne muscular dystrophy family. Author(s): Smith TA, Yau SC, Bobrow M, Abbs SJ. Source: Journal of Medical Genetics. 1999 April; 36(4): 313-5. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10227400&dopt=Abstract
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Identification of a new autosomal dominant limb-girdle muscular dystrophy locus on chromosome 7. Author(s): Speer MC, Vance JM, Grubber JM, Lennon Graham F, Stajich JM, Viles KD, Rogala A, McMichael R, Chutkow J, Goldsmith C, Tim RW, Pericak-Vance MA. Source: American Journal of Human Genetics. 1999 February; 64(2): 556-62. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=9973293&dopt=Abstract
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Identification of a new locus for a peculiar form of congenital muscular dystrophy with early rigidity of the spine, on chromosome 1p35-36. Author(s): Moghadaszadeh B, Desguerre I, Topaloglu H, Muntoni F, Pavek S, Sewry C, Mayer M, Fardeau M, Tome FM, Guicheney P. Source: American Journal of Human Genetics. 1998 June; 62(6): 1439-45. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=9585610&dopt=Abstract
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Identification of a novel truncating mutation (S171X) in the Emerin gene in five members of a Caucasian American family with Emery-Dreifuss muscular dystrophy. Author(s): Menache CC, Brown CA, Donnelly JH, Shapiro F, Darras BT. Source: Human Mutation. 2000 July; 16(1): 94. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10874323&dopt=Abstract
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Identification of altered gene expression in skeletal muscles from Duchenne muscular dystrophy patients. Author(s): Tkatchenko AV, Pietu G, Cros N, Gannoun-Zaki L, Auffray C, Leger JJ, Dechesne CA. Source: Neuromuscular Disorders : Nmd. 2001 April; 11(3): 269-77. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11297942&dopt=Abstract
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Identification of carriers of Duchenne/Becker muscular dystrophy by a novel method based on detection of junction fragments in the dystrophin gene. Author(s): Yamagishi H, Kato S, Hiraishi Y, Ishihara T, Hata J, Matsuo N, Takano T. Source: Journal of Medical Genetics. 1996 December; 33(12): 1027-31. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=9004137&dopt=Abstract
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Identification of lamin A/C ( LMNA) gene mutations in Korean patients with autosomal dominant Emery-Dreifuss muscular dystrophy and limb-girdle muscular dystrophy 1B. Author(s): Ki CS, Hong JS, Jeong GY, Ahn KJ, Choi KM, Kim DK, Kim JW. Source: Journal of Human Genetics. 2002; 47(5): 225-8. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12032588&dopt=Abstract
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Identification of mutations in the gene encoding lamins A/C in autosomal dominant limb girdle muscular dystrophy with atrioventricular conduction disturbances (LGMD1B). Author(s): Muchir A, Bonne G, van der Kooi AJ, van Meegen M, Baas F, Bolhuis PA, de Visser M, Schwartz K. Source: Human Molecular Genetics. 2000 May 22; 9(9): 1453-9. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10814726&dopt=Abstract
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Identification of new mutations in the Emery-Dreifuss muscular dystrophy gene and evidence for genetic heterogeneity of the disease. Author(s): Bione S, Small K, Aksmanovic VM, D'Urso M, Ciccodicola A, Merlini L, Morandi L, Kress W, Yates JR, Warren ST, et al. Source: Human Molecular Genetics. 1995 October; 4(10): 1859-63. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=8595407&dopt=Abstract
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Identification of novel mutations in three families with Emery-Dreifuss muscular dystrophy. Author(s): Klauck SM, Wilgenbus P, Yates JR, Muller CR, Poustka A. Source: Human Molecular Genetics. 1995 October; 4(10): 1853-7. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=8595406&dopt=Abstract
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Immature astrocytes in Fukuyama congenital muscular dystrophy: an immunohistochemical study. Author(s): Yamamoto T, Armstrong D, Shibata N, Kanazawa M, Kobayashi M. Source: Pediatric Neurology. 1999 January; 20(1): 31-7. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10029257&dopt=Abstract
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Immune responses to dystropin: implications for gene therapy of Duchenne muscular dystrophy. Author(s): Ferrer A, Wells KE, Wells DJ. Source: Gene Therapy. 2000 September; 7(17): 1439-46. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11001363&dopt=Abstract
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Immunocytochemical analysis of human muscular dystrophy. Author(s): Sewry CA. Source: Microscopy Research and Technique. 2000 February 1-15; 48(3-4): 142-54. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10679962&dopt=Abstract
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Immunocytochemistry of nuclear domains and Emery-Dreifuss muscular dystrophy pathophysiology. Author(s): Maraldi NM, Lattanzi G, Sabatelli P, Ognibene A, Columbaro M, Capanni C, Rutigliano C, Mattioli E, Squarzoni S. Source: Eur J Histochem. 2003; 47(1): 3-16. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12685553&dopt=Abstract
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Immunohistochemical alterations of dystrophin in congenital muscular dystrophy. Author(s): Werneck LC, Bonilla E. Source: Arquivos De Neuro-Psiquiatria. 1995 September; 53(3-A): 416-23. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=8540815&dopt=Abstract
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Immunohistochemical staining of dystrophin on formalin-fixed paraffin-embedded sections in Duchenne/Becker muscular dystrophy and manifesting carriers of Duchenne muscular dystrophy. Author(s): Hoshino S, Ohkoshi N, Watanabe M, Shoji S. Source: Neuromuscular Disorders : Nmd. 2000 August; 10(6): 425-9. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10899449&dopt=Abstract
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Immunohistochemical study of merosin-negative congenital muscular dystrophy: laminin alpha 2 deficiency in skin biopsy. Author(s): Marbini A, Bellanova MF, Ferrari A, Lodesani M, Gemignani F. Source: Acta Neuropathologica. 1997 August; 94(2): 103-8. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=9255383&dopt=Abstract
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Impact of carrier status determination for Duchenne/Becker muscular dystrophy by computer-assisted laser densitometry. Author(s): Allingham-Hawkins DJ, McGlynn-Steele LK, Brown CA, Sutherland J, Ray PN. Source: American Journal of Medical Genetics. 1998 January 13; 75(2): 171-5. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=9450879&dopt=Abstract
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Impact of nasal ventilation on survival in hypercapnic Duchenne muscular dystrophy. Author(s): Simonds AK, Muntoni F, Heather S, Fielding S. Source: Thorax. 1998 November; 53(11): 949-52. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10193393&dopt=Abstract
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Impact of pregnancy on respiratory capacity in women with muscular dystrophy and kyphoscoliosis. A case report. Author(s): Gamzu R, Shenhav M, Fainaru O, Almog B, Kupferminc M, Lessing JB. Source: J Reprod Med. 2002 January; 47(1): 53-6. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11838313&dopt=Abstract
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Impairment of cardiac autonomic function in patients with Duchenne muscular dystrophy: relationship to myocardial and respiratory function. Author(s): Lanza GA, Dello Russo A, Giglio V, De Luca L, Messano L, Santini C, Ricci E, Damiani A, Fumagalli G, De Martino G, Mangiola F, Bellocci F. Source: American Heart Journal. 2001 May; 141(5): 808-12. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11320370&dopt=Abstract
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Impairment of caveolae formation and T-system disorganization in human muscular dystrophy with caveolin-3 deficiency. Author(s): Minetti C, Bado M, Broda P, Sotgia F, Bruno C, Galbiati F, Volonte D, Lucania G, Pavan A, Bonilla E, Lisanti MP, Cordone G. Source: American Journal of Pathology. 2002 January; 160(1): 265-70. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11786420&dopt=Abstract
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Improved molecular diagnosis of facioscapulohumeral muscular dystrophy (FSHD): validation of the differential double digestion for FSHD. Author(s): Upadhyaya M, Maynard J, Rogers MT, Lunt PW, Jardine P, Ravine D, Harper PS. Source: Journal of Medical Genetics. 1997 June; 34(6): 476-9. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=9192267&dopt=Abstract
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In situ measurements of muscle fiber conduction velocity in Duchenne muscular dystrophy. Author(s): Al-Ani FS, Hamdan FB, Shaikhly KI. Source: Saudi Med J. 2001 March; 22(3): 259-61. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11307114&dopt=Abstract
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In utero fetal muscle biopsy alters diagnosis and carrier risks in Duchenne and Becker muscular dystrophy. Author(s): Evans MI, Krivchenia EL, Johnson MP, Quintero RA, King M, Pegoraro E, Hoffman EP. Source: Fetal Diagnosis and Therapy. 1995 March-April; 10(2): 71-5. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=7794517&dopt=Abstract
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In utero fetal muscle biopsy in the diagnosis of Duchenne muscular dystrophy. Author(s): Ladwig D, Mowat D, Tobias V, Taylor PJ, Buckley MF, McNally G, Challis D. Source: The Australian & New Zealand Journal of Obstetrics & Gynaecology. 2002 February; 42(1): 79-82. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11926646&dopt=Abstract
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In utero fetal muscle biopsy: a precious aid for the prenatal diagnosis of Duchenne muscular dystrophy. Author(s): Heckel S, Favre R, Flori J, Koenig M, Mandel J, Gasser B, Chaigne D. Source: Fetal Diagnosis and Therapy. 1999 May-June; 14(3): 127-32. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10364661&dopt=Abstract
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Incidence of cerebral infarction in Duchenne muscular dystrophy. Author(s): Hanajima R, Kawai M. Source: Muscle & Nerve. 1996 July; 19(7): 928. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=8965857&dopt=Abstract
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Increase in fetal breech presentation in female carriers of Duchenne muscular dystrophy. Author(s): Geifman-Holtzman O, Bernstein IM, Capeless EL, Hawley P, Specht LA, Bianchi DW. Source: American Journal of Medical Genetics. 1997 December 19; 73(3): 276-8. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=9415684&dopt=Abstract
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Increased cerebral choline-compounds in Duchenne muscular dystrophy. Author(s): Kato T, Nishina M, Matsushita K, Hori E, Akaboshi S, Takashima S. Source: Neuroreport. 1997 April 14; 8(6): 1435-7. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=9172149&dopt=Abstract
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Increased expression of IGF-binding protein-5 in Duchenne muscular dystrophy (DMD) fibroblasts correlates with the fibroblast-induced downregulation of DMD myoblast growth: an in vitro analysis. Author(s): Melone MA, Peluso G, Galderisi U, Petillo O, Cotrufo R. Source: Journal of Cellular Physiology. 2000 October; 185(1): 143-53. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10942528&dopt=Abstract
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Increased levels of leukemia inhibitory factor mRNA in muscular dystrophy and human muscle trauma. Author(s): Reardon KA, Kapsa RM, Davis J, Kornberg AJ, Austin L, Choong P, Byrne E. Source: Muscle & Nerve. 2000 June; 23(6): 962-6. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10842275&dopt=Abstract
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Increased number of caveolae and caveolin-3 overexpression in Duchenne muscular dystrophy. Author(s): Repetto S, Bado M, Broda P, Lucania G, Masetti E, Sotgia F, Carbone I, Pavan A, Bonilla E, Cordone G, Lisanti MP, Minetti C. Source: Biochemical and Biophysical Research Communications. 1999 August 11; 261(3): 547-50. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10441463&dopt=Abstract
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Increased solubility of lamins and redistribution of lamin C in X-linked EmeryDreifuss muscular dystrophy fibroblasts. Author(s): Markiewicz E, Venables R, Mauricio-Alvarez-Reyes, Quinlan R, Dorobek M, Hausmanowa-Petrucewicz I, Hutchison C. Source: Journal of Structural Biology. 2002 October-December; 140(1-3): 241-53. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12490172&dopt=Abstract
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Indications for a novel muscular dystrophy pathway. gamma-filamin, the musclespecific filamin isoform, interacts with myotilin. Author(s): van der Ven PF, Wiesner S, Salmikangas P, Auerbach D, Himmel M, Kempa S, Hayess K, Pacholsky D, Taivainen A, Schroder R, Carpen O, Furst DO. Source: The Journal of Cell Biology. 2000 October 16; 151(2): 235-48. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11038172&dopt=Abstract
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Indicators of need for mechanical ventilation in Duchenne muscular dystrophy and spinal muscular atrophy. Author(s): Lyager S, Steffensen B, Juhl B. Source: Chest. 1995 September; 108(3): 779-85. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=7656633&dopt=Abstract
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Inflammatory response in facioscapulohumeral muscular dystrophy (FSHD): immunocytochemical and genetic analyses. Author(s): Arahata K, Ishihara T, Fukunaga H, Orimo S, Lee JH, Goto K, Nonaka I. Source: Muscle & Nerve. 1995; 2: S56-66. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=7739627&dopt=Abstract
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Infraspinatus muscle hypertrophy and wasting of axillary folds as the important signs in Duchenne muscular dystrophy. Author(s): Pradhan S, Mittal B. Source: Clinical Neurology and Neurosurgery. 1995 May; 97(2): 134-8. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=7656486&dopt=Abstract
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Inhalation anesthetics and Duchenne's muscular dystrophy. Author(s): Goresky GV, Cox RG. Source: Canadian Journal of Anaesthesia = Journal Canadien D'anesthesie. 1999 June; 46(6): 525-8. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10391598&dopt=Abstract
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Inheritance of a 38-kb fragment in apparently sporadic facioscapulohumeral muscular dystrophy. Author(s): Vitelli F, Villanova M, Malandrini A, Bruttini M, Piccini M, Merlini L, Guazzi G, Renieri A. Source: Muscle & Nerve. 1999 October; 22(10): 1437-41. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10487912&dopt=Abstract
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Inspiratory flow reserve in boys with Duchenne muscular dystrophy. Author(s): De Bruin PF, Ueki J, Bush A, Y Manzur A, Watson A, Pride NB. Source: Pediatric Pulmonology. 2001 June; 31(6): 451-7. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11389578&dopt=Abstract
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Insulin-like growth factor-I and high protein diet decrease calpain-mediated proteolysis in murine muscular dystrophy. Author(s): Wingertzahn MA, Zdanowicz MM, Slonim AE. Source: Proceedings of the Society for Experimental Biology and Medicine. Society for Experimental Biology and Medicine (New York, N. Y.). 1998 July; 218(3): 244-50. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=9648944&dopt=Abstract
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Integrin alpha 7 beta 1 in muscular dystrophy/myopathy of unknown etiology. Author(s): Pegoraro E, Cepollaro F, Prandini P, Marin A, Fanin M, Trevisan CP, ElMesslemani AH, Tarone G, Engvall E, Hoffman EP, Angelini C. Source: American Journal of Pathology. 2002 June; 160(6): 2135-43. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12057917&dopt=Abstract
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Integrins (alpha7beta1) in muscle function and survival. Disrupted expression in merosin-deficient congenital muscular dystrophy. Author(s): Vachon PH, Xu H, Liu L, Loechel F, Hayashi Y, Arahata K, Reed JC, Wewer UM, Engvall E. Source: The Journal of Clinical Investigation. 1997 October 1; 100(7): 1870-81. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=9312189&dopt=Abstract
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Intelligence and Duchenne muscular dystrophy: full-scale, verbal, and performance intelligence quotients. Author(s): Cotton S, Voudouris NJ, Greenwood KM. Source: Developmental Medicine and Child Neurology. 2001 July; 43(7): 497-501. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11463183&dopt=Abstract
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Inter- and intrachromosomal sub-telomeric rearrangements on 4q35: implications for facioscapulohumeral muscular dystrophy (FSHD) aetiology and diagnosis. Author(s): Lemmers RJ, van der Maarel SM, van Deutekom JC, van der Wielen MJ, Deidda G, Dauwerse HG, Hewitt J, Hofker M, Bakker E, Padberg GW, Frants RR. Source: Human Molecular Genetics. 1998 August; 7(8): 1207-14. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=9668160&dopt=Abstract
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Intestinal pseudoobstruction as a feature of myotonic muscular dystrophy. Author(s): Fuger K, Barnert J, Hopfner W, Wienbeck M. Source: Zeitschrift Fur Gastroenterologie. 1995 September; 33(9): 534-8. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=8525657&dopt=Abstract
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Intraarterial atracurium followed by difficult intubation in a child with congenital muscular dystrophy. Author(s): Gorman A, Dearlove OR. Source: Paediatric Anaesthesia. 1999; 9(3): 277. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10320613&dopt=Abstract
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Intracellular trafficking of emerin, the Emery-Dreifuss muscular dystrophy protein. Author(s): Ostlund C, Ellenberg J, Hallberg E, Lippincott-Schwartz J, Worman HJ. Source: Journal of Cell Science. 1999 June; 112 ( Pt 11): 1709-19. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10318763&dopt=Abstract
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Intrafamilial phenotypic variation in limb-girdle muscular dystrophy type 2C with compound heterozygous mutations. Author(s): Takano A, Bonnemann CG, Honda H, Sakai M, Feener CA, Kunkel LM, Sobue G. Source: Muscle & Nerve. 2000 May; 23(5): 807-10. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10797406&dopt=Abstract
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Intranuclear inclusions in oculopharyngeal muscular dystrophy among Bukhara Jews. Author(s): Blumen SC, Sadeh M, Korczyn AD, Rouche A, Nisipeanu P, Asherov A, Tome FM. Source: Neurology. 1996 May; 46(5): 1324-8. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=8628475&dopt=Abstract
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Intranuclear inclusions in oculopharyngeal muscular dystrophy contain poly(A) binding protein 2. Author(s): Becher MW, Kotzuk JA, Davis LE, Bear DG. Source: Annals of Neurology. 2000 November; 48(5): 812-5. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11079550&dopt=Abstract
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Introduction to muscular dystrophy. Author(s): Porter JD. Source: Microscopy Research and Technique. 2000 February 1-15; 48(3-4): 127-30. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10679960&dopt=Abstract
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Is dystrophin always altered in Becker muscular dystrophy patients? Author(s): Vainzof M, Passos-Bueno MR, Pavanello RC, Zatz M. Source: Journal of the Neurological Sciences. 1995 July; 131(1): 99-104. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=7561956&dopt=Abstract
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Is glutamine a 'conditionally essential' amino acid in Duchenne muscular dystrophy? Author(s): Hankard R, Mauras N, Hammond D, Haymond M, Darmaun D. Source: Clinical Nutrition (Edinburgh, Lothian). 1999 December; 18(6): 365-9. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10634922&dopt=Abstract
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Is there selection in favour of heterozygotes in families with merosin-deficient congenital muscular dystrophy? Author(s): D'Alessandro M, Naom I, Ferlini A, Sewry C, Dubowitz V, Muntoni F. Source: Human Genetics. 1999 October; 105(4): 308-13. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10543397&dopt=Abstract
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It is bundle branch reentry linked to any kind of muscular dystrophy? Author(s): Merino JL, Peinado R. Source: Journal of Cardiovascular Electrophysiology. 1998 December; 9(12): 1397-8. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=9869540&dopt=Abstract
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Juvenile limb-girdle muscular dystrophy. Clinical, histopathological and genetic data from a small community living in the Reunion Island. Author(s): Fardeau M, Hillaire D, Mignard C, Feingold N, Feingold J, Mignard D, de Ubeda B, Collin H, Tome FM, Richard I, Beckmann J. Source: Brain; a Journal of Neurology. 1996 February; 119 ( Pt 1): 295-308. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=8624690&dopt=Abstract
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Lamin A/C mutations with lipodystrophy, cardiac abnormalities, and muscular dystrophy. Author(s): van der Kooi AJ, Bonne G, Eymard B, Duboc D, Talim B, Van der Valk M, Reiss P, Richard P, Demay L, Merlini L, Schwartz K, Busch HF, de Visser M. Source: Neurology. 2002 August 27; 59(4): 620-3. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12196663&dopt=Abstract
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Laminin abnormality in severe childhood autosomal recessive muscular dystrophy. Author(s): Yamada H, Tome FM, Higuchi I, Kawai H, Azibi K, Chaouch M, Roberds SL, Tanaka T, Fujita S, Mitsui T, et al. Source: Laboratory Investigation; a Journal of Technical Methods and Pathology. 1995 June; 72(6): 715-22. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=7783429&dopt=Abstract
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Laminin alpha 2-chain gene mutations in two siblings presenting with limb-girdle muscular dystrophy. Author(s): Naom I, D'Alessandro M, Sewry CA, Philpot J, Manzur AY, Dubowitz V, Muntoni F. Source: Neuromuscular Disorders : Nmd. 1998 October; 8(7): 495-501. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=9829280&dopt=Abstract
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Laminin alpha2 chain-deficient congenital muscular dystrophy: variable epitope expression in severe and mild cases. Author(s): Cohn RD, Herrmann R, Sorokin L, Wewer UM, Voit T. Source: Neurology. 1998 July; 51(1): 94-100. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=9674785&dopt=Abstract
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Laminin alpha2 deficiency and muscular dystrophy; genotype-phenotype correlation in mutant mice. Author(s): Guo LT, Zhang XU, Kuang W, Xu H, Liu LA, Vilquin JT, Miyagoe-Suzuki Y, Takeda S, Ruegg MA, Wewer UM, Engvall E. Source: Neuromuscular Disorders : Nmd. 2003 March; 13(3): 207-15. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12609502&dopt=Abstract
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Laminin alpha2 deficient congenital muscular dystrophy: prenatal diagnosis. Author(s): Nass D, Goldberg I, Sadeh M. Source: Early Human Development. 1999 May; 55(1): 19-24. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10367979&dopt=Abstract
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Laminin alpha2 muscular dystrophy: genotype/phenotype studies of 22 patients. Author(s): Pegoraro E, Marks H, Garcia CA, Crawford T, Mancias P, Connolly AM, Fanin M, Martinello F, Trevisan CP, Angelini C, Stella A, Scavina M, Munk RL, Servidei S, Bonnemann CC, Bertorini T, Acsadi G, Thompson CE, Gagnon D, Hoganson G, Carver V, Zimmerman RA, Hoffman EP. Source: Neurology. 1998 July; 51(1): 101-10. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=9674786&dopt=Abstract
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Late onset and very mild course of Xp21 Becker type muscular dystrophy. Author(s): Bosone I, Bortolotto S, Mongini T, Doriguzzi C, Chiado-Piat L, Ugo I, Mutani R, Palmucci L. Source: Clin Neuropathol. 2001 September-October; 20(5): 196-9. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11594504&dopt=Abstract
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Late onset foot-drop muscular dystrophy with rimmed vacuoles. Author(s): Partanen J, Laulumaa V, Paljarvi L, Partanen K, Naukkarinen A. Source: Journal of the Neurological Sciences. 1994 September; 125(2): 158-67. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=7807161&dopt=Abstract
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Late onset muscular dystrophy proximal myopathy and recurrent falls in the elderly. Author(s): Boonen S. Source: Clinical Rheumatology. 1995 September; 14(5): 586-90. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=8549104&dopt=Abstract
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Late onset muscular dystrophy with cerebral white matter changes due to partial merosin deficiency. Author(s): Tan E, Topaloglu H, Sewry C, Zorlu Y, Naom I, Erdem S, D'Alessandro M, Muntoni F, Dubowitz V. Source: Neuromuscular Disorders : Nmd. 1997 March; 7(2): 85-9. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=9131648&dopt=Abstract
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Learning and transfer in two perceptual-motor skills in Duchenne muscular dystrophy. Author(s): Nakafuji A, Tsuji K. Source: Percept Mot Skills. 2001 October; 93(2): 339-52. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11769887&dopt=Abstract
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Left ventricular function and perfusion in Becker's muscular dystrophy. Author(s): Mansi L, Pace L, Politano L, Rambaldi PF, Di Gregorio F, Raia P, Petretta VR, Nigro G. Source: Journal of Nuclear Medicine : Official Publication, Society of Nuclear Medicine. 1997 April; 38(4): 563-7. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=9098202&dopt=Abstract
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Left ventricular non-compaction in a patient with becker's muscular dystrophy. Author(s): Stollberger C, Finsterer J, Blazek G, Bittner RE. Source: Heart (British Cardiac Society). 1996 October; 76(4): 380. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=8983693&dopt=Abstract
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Lesson of the week: late diagnosis of Duchenne's muscular dystrophy presenting as global developmental delay. Author(s): Essex C, Roper H. Source: Bmj (Clinical Research Ed.). 2001 July 7; 323(7303): 37-8. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11440945&dopt=Abstract
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Lethal congenital muscular dystrophy in two sibs with arthrogryposis multiplex: new entity or variant of cobblestone lissencephaly syndrome? Author(s): Seidahmed MZ, Sunada Y, Ozo CO, Hamid F, Campbell KP, Salih MA. Source: Neuropediatrics. 1996 December; 27(6): 305-10. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=9050048&dopt=Abstract
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Lightweight, modular knee-ankle-foot orthosis for Duchenne muscular dystrophy: design, development, and evaluation. Author(s): Taktak DM, Bowker P. Source: Archives of Physical Medicine and Rehabilitation. 1995 December; 76(12): 115662. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=8540794&dopt=Abstract
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Limb girdle muscular dystrophy in Manitoba Hutterites does not map to any of the known LGMD loci. Author(s): Weiler T, Greenberg CR, Nylen E, Morgan K, Fujiwara TM, Crumley MJ, Zelinski T, Halliday W, Nickel B, Triggs-Raine B, Wrogemann K. Source: American Journal of Medical Genetics. 1997 October 31; 72(3): 363-8. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=9332671&dopt=Abstract
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Limb girdle muscular dystrophy type 2A (CAPN3): mapping using allelic association. Author(s): Lonjou C, Collins A, Beckmann J, Allamand V, Morton N. Source: Human Heredity. 1998 November-December; 48(6): 333-7. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=9813455&dopt=Abstract
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Limb girdle muscular dystrophy type 2A presenting with cardiac arrest. Author(s): Dirik E, Aydin A, Kurul S, Sahin B. Source: Pediatric Neurology. 2001 March; 24(3): 235-7. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11301229&dopt=Abstract
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Limb girdle muscular dystrophy: a pathological and immunohistochemical reevaluation. Author(s): van der Kooi AJ, Ginjaar HB, Busch HF, Wokke JH, Barth PG, de Visser M. Source: Muscle & Nerve. 1998 May; 21(5): 584-90. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=9572237&dopt=Abstract
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Limb girdle muscular dystrophy: a prospective follow-up study of functional impairment. Author(s): Stubgen JP, Stipp A. Source: Muscle & Nerve. 1997 April; 20(4): 453-60. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=9121503&dopt=Abstract
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Limb girdle muscular dystrophy: a quantitative electromyographic study. Author(s): Stubgen JP. Source: Electromyogr Clin Neurophysiol. 1995 October; 35(6): 351-7. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=8785932&dopt=Abstract
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Limb girdle muscular dystrophy: a radiologic and manometric study of the pharynx and esophagus. Author(s): Stubgen JP. Source: Dysphagia. 1996 Winter; 11(1): 25-9. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=8556875&dopt=Abstract
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Limb girdle muscular dystrophy: description of a phenotype. Author(s): Stubgen JP. Source: Muscle & Nerve. 1994 December; 17(12): 1449-55. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=7969245&dopt=Abstract
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Limb girdle muscular dystrophy: weakness and disease duration as predictors of functional impairment. Author(s): Stubgen JP, Lahouter A. Source: Muscle & Nerve. 1994 August; 17(8): 873-80. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=8041394&dopt=Abstract
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Limb-girdle muscular dystrophy 2C: clinical aspects. Author(s): Ben Hamida M, Ben Hamida C, Zouari M, Belal S, Hentati F. Source: Neuromuscular Disorders : Nmd. 1996 December; 6(6): 493-4. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=9027861&dopt=Abstract
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Limb-girdle muscular dystrophy and Miyoshi myopathy in an aboriginal Canadian kindred map to LGMD2B and segregate with the same haplotype. Author(s): Weiler T, Greenberg CR, Nylen E, Halliday W, Morgan K, Eggertson D, Wrogemann K. Source: American Journal of Human Genetics. 1996 October; 59(4): 872-8. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=8808603&dopt=Abstract
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Limb-girdle muscular dystrophy in Guipuzcoa (Basque Country, Spain). Author(s): Urtasun M, Saenz A, Roudaut C, Poza JJ, Urtizberea JA, Cobo AM, Richard I, Garcia Bragado F, Leturcq F, Kaplan JC, Marti Masso JF, Beckmann JS, Lopez de Munain A. Source: Brain; a Journal of Neurology. 1998 September; 121 ( Pt 9): 1735-47. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=9762961&dopt=Abstract
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Limb-girdle muscular dystrophy or spinal muscular atrophy: a source of diagnostic confusion? Author(s): Pogue R, Jackson T, Sayli B, Curtis A, Bushby KM. Source: Journal of Medical Genetics. 1997 November; 34(11): 958-9. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=9391899&dopt=Abstract
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Limb-girdle muscular dystrophy type 2G is caused by mutations in the gene encoding the sarcomeric protein telethonin. Author(s): Moreira ES, Wiltshire TJ, Faulkner G, Nilforoushan A, Vainzof M, Suzuki OT, Valle G, Reeves R, Zatz M, Passos-Bueno MR, Jenne DE. Source: Nature Genetics. 2000 February; 24(2): 163-6. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10655062&dopt=Abstract
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Limb-girdle muscular dystrophy type 2H associated with mutation in TRIM32, a putative E3-ubiquitin-ligase gene. Author(s): Frosk P, Weiler T, Nylen E, Sudha T, Greenberg CR, Morgan K, Fujiwara TM, Wrogemann K. Source: American Journal of Human Genetics. 2002 March; 70(3): 663-72. Epub 2002 January 29. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11822024&dopt=Abstract
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Limb-girdle muscular dystrophy with apparently different clinical courses within sexes in a large inbred kindred. Author(s): Leal GF, da-Silva EO. Source: Journal of Medical Genetics. 1999 September; 36(9): 714-8. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10507732&dopt=Abstract
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Limb-girdle muscular dystrophy. Author(s): Mathews KD, Moore SA. Source: Curr Neurol Neurosci Rep. 2003 January; 3(1): 78-85. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12507416&dopt=Abstract
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Limb-girdle muscular dystrophy: a follow-up study of 79 patients. Author(s): Mahjneh I, Bushby K, Pizzi A, Bashir R, Marconi G. Source: Acta Neurologica Scandinavica. 1996 September; 94(3): 177-89. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=8899051&dopt=Abstract
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Limb-girdle muscular dystrophy: clinical and pathologic reevaluation. Author(s): Yamanouchi Y, Arikawa E, Arahata K, Ozawa E, Nonaka I. Source: Journal of the Neurological Sciences. 1995 March; 129(1): 15-20. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=7751838&dopt=Abstract
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Limb-girdle muscular dystrophy: one gene with different phenotypes, one phenotype with different genes. Author(s): Zatz M, Vainzof M, Passos-Bueno MR. Source: Current Opinion in Neurology. 2000 October; 13(5): 511-7. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11073356&dopt=Abstract
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Limitation of eye movement in merosin-deficient congenital muscular dystrophy. Author(s): Philpot J, Muntoni F. Source: Lancet. 1999 January 23; 353(9149): 297-8. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=9929033&dopt=Abstract
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Linkage analyses in tibial muscular dystrophy. Author(s): Nokelainen P, Udd B, Somer H, Peltonen L. Source: Human Heredity. 1996 March-April; 46(2): 98-107. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=8666419&dopt=Abstract
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Linkage analysis in autosomal recessive limb-girdle muscular dystrophy (AR LGMD) maps a sixth form to 5q33-34 (LGMD2F) and indicates that there is at least one more subtype of AR LGMD. Author(s): Passos-Bueno MR, Moreira ES, Vainzof M, Marie SK, Zatz M. Source: Human Molecular Genetics. 1996 June; 5(6): 815-20. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=8776597&dopt=Abstract
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Linkage of familial dilated cardiomyopathy with conduction defect and muscular dystrophy to chromosome 6q23. Author(s): Messina DN, Speer MC, Pericak-Vance MA, McNally EM. Source: American Journal of Human Genetics. 1997 October; 61(4): 909-17. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=9382102&dopt=Abstract
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Linkage of Miyoshi myopathy (distal autosomal recessive muscular dystrophy) locus to chromosome 2p12-14. Author(s): Bejaoui K, Hirabayashi K, Hentati F, Haines JL, Ben Hamida C, Belal S, Miller RG, McKenna-Yasek D, Weissenbach J, Rowland LP, et al. Source: Neurology. 1995 April; 45(4): 768-72. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=7723968&dopt=Abstract
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Linkage-disequilibrium mapping narrows the Fukuyama-type congenital muscular dystrophy (FCMD) candidate region to <100 kb. Author(s): Toda T, Miyake M, Kobayashi K, Mizuno K, Saito K, Osawa M, Nakamura Y, Kanazawa I, Nakagome Y, Tokunaga K, Nakahori Y. Source: American Journal of Human Genetics. 1996 December; 59(6): 1313-20. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=8940277&dopt=Abstract
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Localization of laminin chains in the human retina: possible implications for congenital muscular dystrophy associated with alpha 2-chain of laminin deficiency. Author(s): Toti P, De Felice C, Malandrini A, Megha T, Cardone C, Villanova M. Source: Neuromuscular Disorders : Nmd. 1997 January; 7(1): 21-5. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=9132136&dopt=Abstract
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Localization of laminin subunits in the central nervous system in Fukuyama congenital muscular dystrophy: an immunohistochemical investigation. Author(s): Yamamoto T, Shibata N, Kanazawa M, Kobayashi M, Komori T, Ikeya K, Kondo E, Saito K, Osawa M. Source: Acta Neuropathologica. 1997 August; 94(2): 173-9. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=9255393&dopt=Abstract
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Localization of merosin in the normal human brain: implications for congenital muscular dystrophy with merosin deficiency. Author(s): Villanova M, Malandrini A, Toti P, Salvestroni R, Six J, Martin JJ, Guazzi GC. Source: J Submicrosc Cytol Pathol. 1996 January; 28(1): 1-4. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=8929621&dopt=Abstract
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Localization of merosin-negative congenital muscular dystrophy to chromosome 6q2 by homozygosity mapping. Author(s): Hillaire D, Leclerc A, Faure S, Topaloglu H, Chiannilkulchai N, Guicheney P, Grinas L, Legos P, Philpot J, Evangelista T, et al. Source: Human Molecular Genetics. 1994 September; 3(9): 1657-61. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=7833925&dopt=Abstract
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Lockhart Clarke (1817-1880): his role in the early history of muscular dystrophy. Author(s): Emery AE, Emery ML. Source: Neuromuscular Disorders : Nmd. 2000 October; 10(7): 530-3. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10996787&dopt=Abstract
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Longitudinal data analysis: an application to construction of a natural history profile of Duchenne muscular dystrophy. Author(s): Hyde SA, Steffensen BF, Floytrup I, Glent S, Kroksmark AK, Salling B, Werlauff U, Erlandsen M. Source: Neuromuscular Disorders : Nmd. 2001 March; 11(2): 165-70. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11257473&dopt=Abstract
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Long-term persistence of donor nuclei in a Duchenne muscular dystrophy patient receiving bone marrow transplantation. Author(s): Gussoni E, Bennett RR, Muskiewicz KR, Meyerrose T, Nolta JA, Gilgoff I, Stein J, Chan YM, Lidov HG, Bonnemann CG, Von Moers A, Morris GE, Den Dunnen JT, Chamberlain JS, Kunkel LM, Weinberg K. Source: The Journal of Clinical Investigation. 2002 September; 110(6): 807-14. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12235112&dopt=Abstract
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Long-term results of spine surgery in Duchenne muscular dystrophy. Author(s): Granata C, Merlini L, Cervellati S, Ballestrazzi A, Giannini S, Corbascio M, Lari S. Source: Neuromuscular Disorders : Nmd. 1996 January; 6(1): 61-8. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=8845720&dopt=Abstract
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Long-term ventilation for patients with Duchenne muscular dystrophy : physicians' beliefs and practices. Author(s): Gibson B. Source: Chest. 2001 March; 119(3): 940-6. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11243978&dopt=Abstract
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Loss of A-type lamin expression compromises nuclear envelope integrity leading to muscular dystrophy. Author(s): Sullivan T, Escalante-Alcalde D, Bhatt H, Anver M, Bhat N, Nagashima K, Stewart CL, Burke B. Source: The Journal of Cell Biology. 1999 November 29; 147(5): 913-20. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10579712&dopt=Abstract
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Loss of plectin causes epidermolysis bullosa with muscular dystrophy: cDNA cloning and genomic organization. Author(s): McLean WH, Pulkkinen L, Smith FJ, Rugg EL, Lane EB, Bullrich F, Burgeson RE, Amano S, Hudson DL, Owaribe K, McGrath JA, McMillan JR, Eady RA, Leigh IM, Christiano AM, Uitto J. Source: Genes & Development. 1996 July 15; 10(14): 1724-35. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=8698233&dopt=Abstract
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Loss of the sarcoglycan complex and sarcospan leads to muscular dystrophy in betasarcoglycan-deficient mice. Author(s): Araishi K, Sasaoka T, Imamura M, Noguchi S, Hama H, Wakabayashi E, Yoshida M, Hori T, Ozawa E. Source: Human Molecular Genetics. 1999 September; 8(9): 1589-98. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10441321&dopt=Abstract
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Low-dose prednisolone treatment in Duchenne and Becker muscular dystrophy. Author(s): Backman E, Henriksson KG. Source: Neuromuscular Disorders : Nmd. 1995 May; 5(3): 233-41. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=7633189&dopt=Abstract
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Lower limb surgery in Duchenne muscular dystrophy. Author(s): Forst J, Forst R. Source: Neuromuscular Disorders : Nmd. 1999 May; 9(3): 176-81. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10382913&dopt=Abstract
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Lung clearance in children with Duchenne muscular dystrophy or spinal muscular atrophy with and without CPAP (continuous positive airway pressure). Author(s): Klefbeck B, Svartengren K, Camner P, Philipson K, Svartengren M, Sejersen T, Mattsson E. Source: Experimental Lung Research. 2001 September; 27(6): 469-84. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11558965&dopt=Abstract
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Lung function in children with Duchenne's muscular dystrophy. Author(s): Tangsrud S, Petersen IL, Lodrup Carlsen KC, Carlsen KH. Source: Respiratory Medicine. 2001 November; 95(11): 898-903. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11716204&dopt=Abstract
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Lung function in Duchenne muscular dystrophy. Author(s): Galasko CS, Williamson JB, Delaney CM. Source: European Spine Journal : Official Publication of the European Spine Society, the European Spinal Deformity Society, and the European Section of the Cervical Spine Research Society. 1995; 4(5): 263-7. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=8581525&dopt=Abstract
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Magnetic resonance spectroscopy evidence of abnormal cardiac energetics in Xp21 muscular dystrophy. Author(s): Crilley JG, Boehm EA, Rajagopalan B, Blamire AM, Styles P, Muntoni F, Hilton-Jones D, Clarke K. Source: Journal of the American College of Cardiology. 2000 November 15; 36(6): 1953-8. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11092670&dopt=Abstract
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Malignant hyperthermia-like episode in Becker muscular dystrophy. Author(s): Kleopa KA, Rosenberg H, Heiman-Patterson T. Source: Anesthesiology. 2000 December; 93(6): 1535-7. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11149452&dopt=Abstract
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Mammalian, yeast, bacterial, and chemical chaperones reduce aggregate formation and death in a cell model of oculopharyngeal muscular dystrophy. Author(s): Bao YP, Cook LJ, O'Donovan D, Uyama E, Rubinsztein DC. Source: The Journal of Biological Chemistry. 2002 April 5; 277(14): 12263-9. Epub 2002 January 16. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11796717&dopt=Abstract
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Mapping of replication origins and termination sites in the Duchenne muscular dystrophy gene. Author(s): Verbovaia LV, Razin SV. Source: Genomics. 1997 October 1; 45(1): 24-30. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=9339357&dopt=Abstract
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Mapping the journey: family carers' perceptions of issues related to end-stage care of individuals with muscular dystrophy or motor neurone disease. Author(s): Dawson S, Kristjanson LJ. Source: Journal of Palliative Care. 2003 Spring; 19(1): 36-42. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12710113&dopt=Abstract
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Massive muscle cell degeneration in the early stage of merosin-deficient congenital muscular dystrophy. Author(s): Hayashi YK, Tezak Z, Momoi T, Nonaka I, Garcia CA, Hoffman EP, Arahata K. Source: Neuromuscular Disorders : Nmd. 2001 May; 11(4): 350-9. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11369186&dopt=Abstract
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Merosin and congenital muscular dystrophy. Author(s): Miyagoe-Suzuki Y, Nakagawa M, Takeda S. Source: Microscopy Research and Technique. 2000 February 1-15; 48(3-4): 181-91. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10679965&dopt=Abstract
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Merosin-deficient congenital muscular dystrophy and cortical dysplasia. Author(s): Brett FM, Costigan D, Farrell MA, Heaphy P, Thornton J, King MD. Source: European Journal of Paediatric Neurology : Ejpn : Official Journal of the European Paediatric Neurology Society. 1998; 2(2): 77-82. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10724100&dopt=Abstract
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Merosin-deficient congenital muscular dystrophy with mental retardation and cerebellar cysts unlinked to the LAMA2, FCMD and MEB loci. Author(s): Talim B, Ferreiro A, Cormand B, Vignier N, Oto A, Gogus S, Cila A, Lehesjoki AE, Pihko H, Guicheney P, Topaloglu H. Source: Neuromuscular Disorders : Nmd. 2000 December; 10(8): 548-52. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11053680&dopt=Abstract
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Merosin-deficient congenital muscular dystrophy with mental retardation and cerebellar cysts, unlinked to the LAMA2, FCMD, MEB and CMD1B loci, in three Tunisian patients. Author(s): Triki C, Louhichi N, Meziou M, Choyakh F, Kechaou MS, Jlidi R, Mhiri C, Fakhfakh F, Ayadi H. Source: Neuromuscular Disorders : Nmd. 2003 January; 13(1): 4-12. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12467726&dopt=Abstract
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Merosin-deficient congenital muscular dystrophy, autosomal recessive (MDC1A, MIM#156225, LAMA2 gene coding for alpha2 chain of laminin). Author(s): Allamand V, Guicheney P. Source: European Journal of Human Genetics : Ejhg. 2002 February; 10(2): 91-4. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11938437&dopt=Abstract
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Merosin-negative congenital muscular dystrophy associated with extensive brain abnormalities. Author(s): Sunada Y, Edgar TS, Lotz BP, Rust RS, Campbell KP. Source: Neurology. 1995 November; 45(11): 2084-9. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=7501163&dopt=Abstract
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Merosin-positive congenital muscular dystrophy in two siblings with cataract and slight mental retardation. Author(s): Reed UC, Tsanaclis AM, Vainzof M, Marie SK, Carvalho MS, Roizenblatt J, Pedreira CC, Diament A, Levy JA. Source: Brain & Development. 1999 June; 21(4): 274-8. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10392752&dopt=Abstract
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Merosin-positive congenital muscular dystrophy with mental retardation and cataracts: a new entity in two families. Author(s): Topaloglu H, Yetuk M, Talim B, Akcoren Z, Caglar M. Source: European Journal of Paediatric Neurology : Ejpn : Official Journal of the European Paediatric Neurology Society. 1997; 1(4): 127-31. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10728208&dopt=Abstract
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Merosin-positive congenital muscular dystrophy with mental retardation, microcephaly and central nervous system abnormalities unlinked to the Fukuyama muscular dystrophy and muscular-eye-brain loci: report of three siblings. Author(s): Ruggieri V, Lubieniecki F, Meli F, Diaz D, Ferragut E, Saito K, Brockington M, Muntoni F, Fukuyama Y, Taratuto AL. Source: Neuromuscular Disorders : Nmd. 2001 September; 11(6-7): 570-8. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11525887&dopt=Abstract
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Mild muscular dystrophy due to a nonsense mutation in the LAMA2 gene resulting in exon skipping. Author(s): Di Blasi C, He Y, Morandi L, Cornelio F, Guicheney P, Mora M. Source: Brain; a Journal of Neurology. 2001 April; 124(Pt 4): 698-704. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11287370&dopt=Abstract
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Modular flexibility of dystrophin: implications for gene therapy of Duchenne muscular dystrophy. Author(s): Harper SQ, Hauser MA, DelloRusso C, Duan D, Crawford RW, Phelps SF, Harper HA, Robinson AS, Engelhardt JF, Brooks SV, Chamberlain JS. Source: Nature Medicine. 2002 March; 8(3): 253-61. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11875496&dopt=Abstract
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Molecular analysis of 4q35 rearrangements in fascioscapulohumeral muscular dystrophy (FSHD): application to family studies for a correct genetic advice and a reliable prenatal diagnosis of the disease. Author(s): Galluzzi G, Deidda G, Cacurri S, Colantoni L, Piazzo N, Vigneti E, Ricci E, Servidei S, Merico B, Pachi A, Brambati B, Mangiola F, Tonali P, Felicetti L. Source: Neuromuscular Disorders : Nmd. 1999 May; 9(3): 190-8. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10382915&dopt=Abstract
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Molecular analysis of p94 and its application to diagnosis of limb girdle muscular dystrophy type 2A. Author(s): Sorimachi H, Ono Y, Suzuki K. Source: Methods in Molecular Biology (Clifton, N.J.). 2000; 144: 75-84. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10818750&dopt=Abstract
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Molecular approaches to therapy for Duchenne and limb-girdle muscular dystrophy. Author(s): Stedman HH. Source: Curr Opin Mol Ther. 2001 August; 3(4): 350-6. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11525558&dopt=Abstract
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Molecular diagnosis and counseling in a family presenting compound heterozygosity for autosomal recessive limb-girdle muscular dystrophy. Author(s): Dos Santos MR, Vieira EM, Reis Lima M. Source: Genet Couns. 2001; 12(3): 223-9. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11693784&dopt=Abstract
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Molecular diagnosis of Duchenne/Becker muscular dystrophy by polymerase chain reaction and microsatellite analysis. Author(s): Kim UK, Chae JJ, Lee SH, Lee CC, Namkoong Y. Source: Molecules and Cells. 2002 June 30; 13(3): 385-8. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12132577&dopt=Abstract
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Molecular diagnosis of facioscapulohumeral muscular dystrophy. Author(s): Upadhyaya M, Cooper DN. Source: Expert Rev Mol Diagn. 2002 March; 2(2): 160-71. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11962336&dopt=Abstract
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Molecular pathophysiology and targeted therapeutics for muscular dystrophy. Author(s): Hoffman EP, Dressman D. Source: Trends in Pharmacological Sciences. 2001 September; 22(9): 465-70. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11543874&dopt=Abstract
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Morphological changes in muscle fibers in oculopharyngeal muscular dystrophy. Author(s): Tome FM, Chateau D, Helbling-Leclerc A, Fardeau M. Source: Neuromuscular Disorders : Nmd. 1997 October; 7 Suppl 1: S63-9. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=9392019&dopt=Abstract
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Motor unit changes in inflammatory myopathy and progressive muscular dystrophy. Author(s): Rowinska-Marcinska K, Szmidt-Salkowska E, Kopec A, Wawro A, Karwanska A. Source: Electromyogr Clin Neurophysiol. 2000 October-November; 40(7): 431-9. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11142114&dopt=Abstract
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MR imaging of pelvic and thigh muscles in congenital muscular dystrophy. Author(s): Oto A, Aydingoz U, Basgun N, Talim B, Karaagaoglu E, Topaloglu H. Source: Turk J Pediatr. 2001 January-March; 43(1): 44-51. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11297158&dopt=Abstract
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Multiple regulatory events controlling the expression and localization of utrophin in skeletal muscle fibers: insights into a therapeutic strategy for Duchenne muscular dystrophy. Author(s): Jasmin BJ, Angus LM, Belanger G, Chakkalakal JV, Gramolini AO, Lunde JA, Stocksley MA, Thompson J. Source: Journal of Physiology, Paris. 2002 January-March; 96(1-2): 31-42. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11755781&dopt=Abstract
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Muscle and joint elastic properties during elbow flexion in Duchenne muscular dystrophy. Author(s): Cornu C, Goubel F, Fardeau M. Source: The Journal of Physiology. 2001 June 1; 533(Pt 2): 605-16. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11389216&dopt=Abstract
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Muscle magnetic resonance imaging in patients with congenital muscular dystrophy and Ullrich phenotype. Author(s): Mercuri E, Cini C, Pichiecchio A, Allsop J, Counsell S, Zolkipli Z, Messina S, Kinali M, Brown SC, Jimenez C, Brockington M, Yuva Y, Sewry CA, Muntoni F. Source: Neuromuscular Disorders : Nmd. 2003 September; 13(7-8): 554-8. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12921792&dopt=Abstract
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Muscular dystrophy and neuronal migration disorder caused by mutations in a glycosyltransferase, POMGnT1. Author(s): Yoshida A, Kobayashi K, Manya H, Taniguchi K, Kano H, Mizuno M, Inazu T, Mitsuhashi H, Takahashi S, Takeuchi M, Herrmann R, Straub V, Talim B, Voit T, Topaloglu H, Toda T, Endo T. Source: Developmental Cell. 2001 November; 1(5): 717-24. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11709191&dopt=Abstract
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Muscular dystrophy campaign sponsored workshop: recommendation for respiratory care of children with spinal muscular atrophy type II and III. 13th February 2002, London, UK. Author(s): Manzur AY, Muntoni F, Simonds A. Source: Neuromuscular Disorders : Nmd. 2003 February; 13(2): 184-9. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12565919&dopt=Abstract
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Muscular dystrophy due to dysferlin deficiency in Libyan Jews. Clinical and genetic features. Author(s): Argov Z, Sadeh M, Mazor K, Soffer D, Kahana E, Eisenberg I, MitraniRosenbaum S, Richard I, Beckmann J, Keers S, Bashir R, Bushby K, Rosenmann H. Source: Brain; a Journal of Neurology. 2000 June; 123 ( Pt 6): 1229-37. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10825360&dopt=Abstract
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Muscular dystrophy into the new millennium. Author(s): Emery AE. Source: Neuromuscular Disorders : Nmd. 2002 May; 12(4): 343-9. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12062251&dopt=Abstract
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Muscular dystrophy meets the gene chip: new insights into disease pathogenesis. Author(s): Chamberlain JS. Source: The Journal of Cell Biology. 2000 December 11; 151(6): F43-5. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11121429&dopt=Abstract
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Muscular dystrophy meets the mesangioblast. Author(s): Schubert C. Source: Nature Medicine. 2003 August; 9(8): 999. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12894161&dopt=Abstract
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Muscular dystrophy through an evolutionary lens. Author(s): Roberts R. Source: Lancet. 2001 December; 358 Suppl: S25. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11784574&dopt=Abstract
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Muscular dystrophy. Author(s): Arahata K. Source: Neuropathology : Official Journal of the Japanese Society of Neuropathology. 2000 September; 20 Suppl: S34-41. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11037185&dopt=Abstract
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Muscular dystrophy. Author(s): Roland EH. Source: Pediatrics in Review / American Academy of Pediatrics. 2000 July; 21(7): 233-7; Quiz 238. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10878185&dopt=Abstract
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Muscular dystrophy. Author(s): Weir A. Source: Current Biology : Cb. 2000 February 10; 10(3): R92. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10679334&dopt=Abstract
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Muscular dystrophy: from gene to patient. Author(s): Hopkins JC, Bia BL, Crilley JG, Boehm EA, Sang AE, Tinsley JM, King LM, Radda GK, Davies KE, Clarke K. Source: Magma (New York, N.Y.). 2000 November; 11(1-2): 7-9. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11186993&dopt=Abstract
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Muscular dystrophy: historical overview and classification in the genetic era. Author(s): Kissel JT, Mendell JR. Source: Seminars in Neurology. 1999; 19(1): 5-7. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10711984&dopt=Abstract
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Muscular dystrophy: the worm turns to genetic disease. Author(s): Chamberlain JS, Benian GM. Source: Current Biology : Cb. 2000 November 2; 10(21): R795-7. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11084353&dopt=Abstract
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Muscular dystrophy: toxic RNA to blame. Author(s): Clough J. Source: Drug Discovery Today. 2002 October 1; 7(19): 982-4. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12546908&dopt=Abstract
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Muscular dystrophy--reason for optimism? Author(s): Burton EA, Davies KE. Source: Cell. 2002 January 11; 108(1): 5-8. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11792315&dopt=Abstract
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Mutation of Large, which encodes a putative glycosyltransferase, in an animal model of muscular dystrophy. Author(s): Grewal PK, Hewitt JE. Source: Biochimica Et Biophysica Acta. 2002 December 19; 1573(3): 216-24. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12417403&dopt=Abstract
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Mutations in calpain 3 associated with limb girdle muscular dystrophy: analysis by molecular modeling and by mutation in m-calpain. Author(s): Jia Z, Petrounevitch V, Wong A, Moldoveanu T, Davies PL, Elce JS, Beckmann JS. Source: Biophysical Journal. 2001 June; 80(6): 2590-6. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11371436&dopt=Abstract
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Mutations in COL6A3 cause severe and mild phenotypes of Ullrich congenital muscular dystrophy. Author(s): Demir E, Sabatelli P, Allamand V, Ferreiro A, Moghadaszadeh B, Makrelouf M, Topaloglu H, Echenne B, Merlini L, Guicheney P. Source: American Journal of Human Genetics. 2002 June; 70(6): 1446-58. Epub 2002 April 24. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11992252&dopt=Abstract
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Mutations in SEPN1 cause congenital muscular dystrophy with spinal rigidity and restrictive respiratory syndrome. Author(s): Moghadaszadeh B, Petit N, Jaillard C, Brockington M, Roy SQ, Merlini L, Romero N, Estournet B, Desguerre I, Chaigne D, Muntoni F, Topaloglu H, Guicheney P. Source: Nature Genetics. 2001 September; 29(1): 17-8. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11528383&dopt=Abstract
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Mutations in the delta-sarcoglycan gene are a rare cause of autosomal recessive limbgirdle muscular dystrophy (LGMD2). Author(s): Duggan DJ, Manchester D, Stears KP, Mathews DJ, Hart C, Hoffman EP. Source: Neurogenetics. 1997 May; 1(1): 49-58. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10735275&dopt=Abstract
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Mutations in the fukutin-related protein gene (FKRP) cause a form of congenital muscular dystrophy with secondary laminin alpha2 deficiency and abnormal glycosylation of alpha-dystroglycan. Author(s): Brockington M, Blake DJ, Prandini P, Brown SC, Torelli S, Benson MA, Ponting CP, Estournet B, Romero NB, Mercuri E, Voit T, Sewry CA, Guicheney P, Muntoni F. Source: American Journal of Human Genetics. 2001 December; 69(6): 1198-209. Epub 2001 October 08. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11592034&dopt=Abstract
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Mutations in the fukutin-related protein gene (FKRP) identify limb girdle muscular dystrophy 2I as a milder allelic variant of congenital muscular dystrophy MDC1C. Author(s): Brockington M, Yuva Y, Prandini P, Brown SC, Torelli S, Benson MA, Herrmann R, Anderson LV, Bashir R, Burgunder JM, Fallet S, Romero N, Fardeau M, Straub V, Storey G, Pollitt C, Richard I, Sewry CA, Bushby K, Voit T, Blake DJ, Muntoni F. Source: Human Molecular Genetics. 2001 December 1; 10(25): 2851-9. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11741828&dopt=Abstract
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Mutations in the laminin alpha 2-chain gene (LAMA2) cause merosin-deficient congenital muscular dystrophy. Author(s): Helbling-Leclerc A, Zhang X, Topaloglu H, Cruaud C, Tesson F, Weissenbach J, Tome FM, Schwartz K, Fardeau M, Tryggvason K, et al. Source: Nature Genetics. 1995 October; 11(2): 216-8. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=7550355&dopt=Abstract
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Mutations of the selenoprotein N gene, which is implicated in rigid spine muscular dystrophy, cause the classical phenotype of multiminicore disease: reassessing the nosology of early-onset myopathies. Author(s): Ferreiro A, Quijano-Roy S, Pichereau C, Moghadaszadeh B, Goemans N, Bonnemann C, Jungbluth H, Straub V, Villanova M, Leroy JP, Romero NB, Martin JJ, Muntoni F, Voit T, Estournet B, Richard P, Fardeau M, Guicheney P. Source: American Journal of Human Genetics. 2002 October; 71(4): 739-49. Epub 2002 August 21. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12192640&dopt=Abstract
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Myoblast transfer in the treatment of Duchenne's muscular dystrophy. Author(s): Mendell JR, Kissel JT, Amato AA, King W, Signore L, Prior TW, Sahenk Z, Benson S, McAndrew PE, Rice R, et al. Source: The New England Journal of Medicine. 1995 September 28; 333(13): 832-8. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=7651473&dopt=Abstract
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Myocardial integrated ultrasound backscatter in patients with Duchenne's progressive muscular dystrophy. Author(s): Mori K, Manabe T, Nii M, Hayabuchi Y, Kuroda Y, Tatara K. Source: Heart (British Cardiac Society). 2001 September; 86(3): 341-2. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11514494&dopt=Abstract
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Myocarditis associated with parvovirus B19 infection in two siblings with merosindeficient congenital muscular dystrophy. Author(s): Beghetti M, Gervaix A, Haenggeli CA, Berner M, Rimensberger PC. Source: European Journal of Pediatrics. 2000 January-February; 159(1-2): 135-6. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10653351&dopt=Abstract
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Myogenic stem cells from the bone marrow: a therapeutic alternative for muscular dystrophy? Author(s): Ferrari G, Mavilio F. Source: Neuromuscular Disorders : Nmd. 2002 October; 12 Suppl 1: S7-10. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12206789&dopt=Abstract
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Myotilin is mutated in limb girdle muscular dystrophy 1A. Author(s): Hauser MA, Horrigan SK, Salmikangas P, Torian UM, Viles KD, Dancel R, Tim RW, Taivainen A, Bartoloni L, Gilchrist JM, Stajich JM, Gaskell PC, Gilbert JR, Vance JM, Pericak-Vance MA, Carpen O, Westbrook CA, Speer MC. Source: Human Molecular Genetics. 2000 September 1; 9(14): 2141-7. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10958653&dopt=Abstract
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Neonatal screening for Duchenne muscular dystrophy: a novel semiquantitative application of the bioluminescence test for creatine kinase in a pilot national program in Cyprus. Author(s): Drousiotou A, Ioannou P, Georgiou T, Mavrikiou E, Christopoulos G, Kyriakides T, Voyasianos M, Argyriou A, Middleton L. Source: Genetic Testing. 1998; 2(1): 55-60. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10464597&dopt=Abstract
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Neurogenic involvement in a case of oculopharyngeal muscular dystrophy. Author(s): Boukriche Y, Maisonobe T, Masson C. Source: Muscle & Nerve. 2002 January; 25(1): 98-101. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11754191&dopt=Abstract
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Neuronal nitric oxide synthase and dystrophin-deficient muscular dystrophy. Author(s): Chang WJ, Iannaccone ST, Lau KS, Masters BS, McCabe TJ, McMillan K, Padre RC, Spencer MJ, Tidball JG, Stull JT. Source: Proceedings of the National Academy of Sciences of the United States of America. 1996 August 20; 93(17): 9142-7. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=8799168&dopt=Abstract
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New aspect of the research on limb-girdle muscular dystrophy 2A: a molecular biologic and biochemical approach to pathology. Author(s): Ono Y, Sorimachi H, Suzuki K. Source: Trends in Cardiovascular Medicine. 1999 July; 9(5): 114-8. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10639725&dopt=Abstract
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New aspects of calcium signaling in skeletal muscle cells: implications in Duchenne muscular dystrophy. Author(s): Gailly P. Source: Biochimica Et Biophysica Acta. 2002 November 4; 1600(1-2): 38-44. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12445457&dopt=Abstract
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New clinical sign in Duchenne muscular dystrophy. Author(s): Pradhan S. Source: Pediatric Neurology. 1994 November; 11(4): 298-300. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=7702689&dopt=Abstract
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New missense mutation in the alpha-sarcoglycan gene in a Japanese patient with severe childhood autosomal recessive muscular dystrophy with incomplete alphasarcoglycan deficiency. Author(s): Higuchi I, Iwaki H, Kawai H, Endo T, Kunishige M, Fukunaga H, Nakagawa M, Arimura K, Osame M. Source: Journal of the Neurological Sciences. 1997 December 9; 153(1): 100-5. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=9455986&dopt=Abstract
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New molecular mechanism for Ullrich congenital muscular dystrophy: a heterozygous in-frame deletion in the COL6A1 gene causes a severe phenotype. Author(s): Pan TC, Zhang RZ, Sudano DG, Marie SK, Bonnemann CG, Chu ML. Source: American Journal of Human Genetics. 2003 August; 73(2): 355-69. Epub 2003 July 01. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12840783&dopt=Abstract
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Newborn screening for Duchenne muscular dystrophy. Author(s): Parsons EP, Bradley DM, Clarke AJ. Source: Archives of Disease in Childhood. 2003 January; 88(1): 91-2. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12495984&dopt=Abstract
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Newborn screening for Duchenne muscular dystrophy: a psychosocial study. Author(s): Parsons EP, Clarke AJ, Hood K, Lycett E, Bradley DM. Source: Archives of Disease in Childhood. Fetal and Neonatal Edition. 2002 March; 86(2): F91-5. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11882550&dopt=Abstract
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Newly recognized exons induced by a splicing abnormality from an intronic mutation of the dystrophin gene resulting in Duchenne muscular dystrophy. Mutations in brief no. 213. Online. Author(s): Ikezawa M, Nishino I, Goto Y, Miike T, Nonaka I. Source: Human Mutation. 1999; 13(2): 170. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10094556&dopt=Abstract
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Nine-year follow-up study of heart rate variability in patients with Duchenne-type progressive muscular dystrophy. Author(s): Yotsukura M, Fujii K, Katayama A, Tomono Y, Ando H, Sakata K, Ishihara T, Ishikawa K. Source: American Heart Journal. 1998 August; 136(2): 289-96. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=9704692&dopt=Abstract
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Nitric oxide synthase complexed with dystrophin and absent from skeletal muscle sarcolemma in Duchenne muscular dystrophy. Author(s): Brenman JE, Chao DS, Xia H, Aldape K, Bredt DS. Source: Cell. 1995 September 8; 82(5): 743-52. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=7545544&dopt=Abstract
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Nitric oxide synthase I (NOS-I) is deficient in the sarcolemma of striated muscle fibers in patients with Duchenne muscular dystrophy, suggesting an association with dystrophin. Author(s): Grozdanovic Z, Gosztonyi G, Gossrau R. Source: Acta Histochemica. 1996 January; 98(1): 61-9. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=9054190&dopt=Abstract
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No evidence for heterogeneity in oculopharyngeal muscular dystrophy. Author(s): Kress W, Halliger-Keller B, Grimm T, Porschke H, Engelhardt A, Goebel HH, Muller-Mysok B. Source: Journal of Medical Genetics. 1998 July; 35(7): 613-4. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=9678711&dopt=Abstract
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No improvement in delay in diagnosis of Duchenne muscular dystrophy. Author(s): Marshall PD, Galasko CS. Source: Lancet. 1995 March 4; 345(8949): 590-1. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=7605512&dopt=Abstract
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NO skeletal muscle derived relaxing factor in Duchenne muscular dystrophy. Author(s): Bredt DS. Source: Proceedings of the National Academy of Sciences of the United States of America. 1998 December 8; 95(25): 14592-3. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=9843933&dopt=Abstract
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NO vascular control in Duchenne muscular dystrophy. Author(s): Crosbie RH. Source: Nature Medicine. 2001 January; 7(1): 27-9. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11135610&dopt=Abstract
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Nocturnal oxygenation and prognosis in Duchenne muscular dystrophy. Author(s): Phillips MF, Smith PE, Carroll N, Edwards RH, Calverley PM. Source: American Journal of Respiratory and Critical Care Medicine. 1999 July; 160(1): 198-202. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10390400&dopt=Abstract
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Nocturnal oxygenation and prognosis in Duchenne muscular dystrophy. Author(s): Ishikawa Y, Bach JR. Source: American Journal of Respiratory and Critical Care Medicine. 2000 February; 161(2 Pt 1): 675-6. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10673215&dopt=Abstract
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Non-Hodgkin's lymphoma of the ascending colon in a patient with becker muscular dystrophy: report of a case. Author(s): Uotani H, Hirokawa S, Saito F, Tauchi K, Shimoda M, Ishizawa S, Kawaguchi M, Nomura K, Kanegane H, Tsukada K. Source: Surgery Today. 2001; 31(11): 1016-9. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11766073&dopt=Abstract
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Noninvasive ventilation during percutaneous gastrostomy placement in Duchenne muscular dystrophy. Author(s): Pope JF, Birnkrant DJ, Martin JE, Repucci AH. Source: Pediatric Pulmonology. 1997 June; 23(6): 468-71. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=9220532&dopt=Abstract
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Nonmuscular involvement in merosin-negative congenital muscular dystrophy. Author(s): Gilhuis HJ, ten Donkelaar HJ, Tanke RB, Vingerhoets DM, Zwarts MJ, Verrips A, Gabreels FJ. Source: Pediatric Neurology. 2002 January; 26(1): 30-6. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11814732&dopt=Abstract
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Nonsense mutations in a Becker muscular dystrophy and an intermediate patient. Author(s): Prior TW, Bartolo C, Papp AC, Snyder PJ, Sedra MS, Burghes AH, Mendell JR. Source: Human Mutation. 1996; 7(1): 72-5. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=8664908&dopt=Abstract
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Normal calcium homeostasis in dystrophin-expressing facioscapulohumeral muscular dystrophy myotubes. Author(s): Vandebrouck C, Imbert N, Constantin B, Duport G, Raymond G, Cognard C. Source: Neuromuscular Disorders : Nmd. 2002 March; 12(3): 266-72. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11801398&dopt=Abstract
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Normal calpain expression in genetically confirmed limb-girdle muscular dystrophy type 2A. Author(s): Talim B, Ognibene A, Mattioli E, Richard I, Anderson LV, Merlini L. Source: Neurology. 2001 March 13; 56(5): 692-3. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11245732&dopt=Abstract
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Normal expression of adhalin and merosin in ovine congenital progressive muscular dystrophy. Author(s): Johnsen RD, Laing NG, Huxtable CR, Kakulas BA. Source: Aust Vet J. 1997 March; 75(3): 215-6. No Abstract Available. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=9088516&dopt=Abstract
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Normalization of creatine kinase level during arthritis in a patient with Becker muscular dystrophy. Author(s): Maegaki Y, Ogura K, Maeoka Y, Takeshita K. Source: Neurology. 1999 January 1; 52(1): 172-4. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=9921868&dopt=Abstract
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Notched T wave as evidence of autonomic nervous lability in Duchenne progressive muscular dystrophy. Author(s): Maruyama T, Fujino T, Fukuoka Y, Tsukamoto K, Mawatari S. Source: Japanese Heart Journal. 1995 November; 36(6): 741-50. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=8627980&dopt=Abstract
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Novel 3678delA mutation in exon 26 of the dystrophin gene causing Duchenne muscular dystrophy. Author(s): Agarwal-Mawal A, Vanasse M, Simard LR. Source: Human Mutation. 1998; Suppl 1: S23-4. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=9452029&dopt=Abstract
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Novel and recurrent mutations in lamin A/C in patients with Emery-Dreifuss muscular dystrophy. Author(s): Brown CA, Lanning RW, McKinney KQ, Salvino AR, Cherniske E, Crowe CA, Darras BT, Gominak S, Greenberg CR, Grosmann C, Heydemann P, Mendell JR, Pober BR, Sasaki T, Shapiro F, Simpson DA, Suchowersky O, Spence JE. Source: American Journal of Medical Genetics. 2001 September 1; 102(4): 359-67. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11503164&dopt=Abstract
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Novel compound heterozygous laminina2-chain gene (LAMA2) mutations in congenital muscular dystrophy. Mutations in brief no. 159. Online. Author(s): Mendell JT, Panicker SG, Tsao CY, Feng B, Sahenk Z, Marzluf GA, Mendell JR. Source: Human Mutation. 1998; 12(2): 135. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10694916&dopt=Abstract
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Novel compound heterozygous mutations in the plectin gene in epidermolysis bullosa with muscular dystrophy and the use of protein truncation test for detection of premature termination codon mutations. Author(s): Dang M, Pulkkinen L, Smith FJ, McLean WH, Uitto J. Source: Laboratory Investigation; a Journal of Technical Methods and Pathology. 1998 February; 78(2): 195-204. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=9484717&dopt=Abstract
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Novel deletion at the M and P promoters of the human dystrophin gene associated with a Duchenne muscular dystrophy. Author(s): Frisso G, Sampaolo S, Pastore L, Carlomagno A, Calise RM, Di Iorio G, Salvatore F. Source: Neuromuscular Disorders : Nmd. 2002 June; 12(5): 494-7. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12031623&dopt=Abstract
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Novel mutations and genotype-phenotype relationships in 107 families with Fukuyama-type congenital muscular dystrophy (FCMD). Author(s): Kondo-Iida E, Kobayashi K, Watanabe M, Sasaki J, Kumagai T, Koide H, Saito K, Osawa M, Nakamura Y, Toda T. Source: Human Molecular Genetics. 1999 November; 8(12): 2303-9. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10545611&dopt=Abstract
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Nuclear accumulation of expanded PABP2 gene product in oculopharyngeal muscular dystrophy. Author(s): Uyama E, Tsukahara T, Goto K, Kurano Y, Ogawa M, Kim YJ, Uchino M, Arahata K. Source: Muscle & Nerve. 2000 October; 23(10): 1549-54. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11003790&dopt=Abstract
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Nuclear alterations in autosomal-dominant Emery-Dreifuss muscular dystrophy. Author(s): Sabatelli P, Lattanzi G, Ognibene A, Columbaro M, Capanni C, Merlini L, Maraldi NM, Squarzoni S. Source: Muscle & Nerve. 2001 June; 24(6): 826-9. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11360268&dopt=Abstract
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Nuclear changes in a case of X-linked Emery-Dreifuss muscular dystrophy. Author(s): Ognibene A, Sabatelli P, Petrini S, Squarzoni S, Riccio M, Santi S, Villanova M, Palmeri S, Merlini L, Maraldi NM. Source: Muscle & Nerve. 1999 July; 22(7): 864-9. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10398203&dopt=Abstract
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Nuclear envelope defects associated with LMNA mutations cause dilated cardiomyopathy and Emery-Dreifuss muscular dystrophy. Author(s): Raharjo WH, Enarson P, Sullivan T, Stewart CL, Burke B. Source: Journal of Cell Science. 2001 December; 114(Pt 24): 4447-57. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11792810&dopt=Abstract
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Nuclear inclusions in oculopharyngeal muscular dystrophy consist of poly(A) binding protein 2 aggregates which sequester poly(A) RNA. Author(s): Calado A, Tome FM, Brais B, Rouleau GA, Kuhn U, Wahle E, Carmo-Fonseca M. Source: Human Molecular Genetics. 2000 September 22; 9(15): 2321-8. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11001936&dopt=Abstract
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Nursing practice management: muscular dystrophy. Author(s): Harrigan J. Source: J Sch Nurs. 1996 April; 12(2): 38-40. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=8704385&dopt=Abstract
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Nutritional assessment in Duchenne muscular dystrophy. Author(s): Willig TN, Carlier L, Legrand M, Riviere H, Navarro J. Source: Developmental Medicine and Child Neurology. 1993 December; 35(12): 1074-82. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=8253288&dopt=Abstract
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Obstetric aspects in women with facioscapulohumeral muscular dystrophy, limbgirdle muscular dystrophy, and congenital myopathies. Author(s): Rudnik-Schoneborn S, Glauner B, Rohrig D, Zerres K. Source: Archives of Neurology. 1997 July; 54(7): 888-94. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=9236578&dopt=Abstract
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Obstructive apnoeas in Duchenne muscular dystrophy. Author(s): Khan Y, Heckmatt JZ. Source: Thorax. 1994 February; 49(2): 157-61. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=8128406&dopt=Abstract
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Occidental-type cerebromuscular dystrophy versus congenital muscular dystrophy with merosin deficiency. Author(s): Castro-Gago M. Source: Child's Nervous System : Chns : Official Journal of the International Society for Pediatric Neurosurgery. 1998 October; 14(10): 531. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=9840374&dopt=Abstract
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Occipito-temporal polymicrogyria and subclinical muscular dystrophy. Author(s): Zolkipli Z, Hartley L, Brown S, Rutherford M, Cowan F, Mercuri E, Muntoni F. Source: Neuropediatrics. 2003 April; 34(2): 92-5. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12776231&dopt=Abstract
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Occurrence of two different intragenic deletions in two male relatives affected with Duchenne muscular dystrophy. Author(s): Mostacciuolo ML, Miorin M, Vitiello L, Rampazzo A, Fanin M, Angelini C, Danieli GA. Source: American Journal of Medical Genetics. 1994 March 1; 50(1): 84-6. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=8160758&dopt=Abstract
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Octreotide enhances positive calcium balance in Duchenne muscular dystrophy. Author(s): Nutting DF, Schriock EA, Palmieri GM, Bittle JB, Elmendorf BJ, Horner LH, Edwards MC, Griffin JW, Sacks HS, Bertorini TE. Source: The American Journal of the Medical Sciences. 1995 September; 310(3): 91-8. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=7668311&dopt=Abstract
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Oculopharyngeal muscular dystrophy (OPMD) due to a small duplication in the PABPN1 gene. Author(s): van der Sluijs BM, van Engelen BG, Hoefsloot LH. Source: Human Mutation. 2003 May; 21(5): 553. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12673802&dopt=Abstract
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Oculopharyngeal muscular dystrophy (OPMD)--report and genetic studies of an Australian kindred. Author(s): Teh BT, Sullivan AA, Farnebo F, Zander C, Li FY, Strachan N, Schalling M, Larsson C, Sandstrom P. Source: Clinical Genetics. 1997 January; 51(1): 52-5. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=9084936&dopt=Abstract
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Oculopharyngeal muscular dystrophy complicating airway management. Author(s): Christopher K, Horkan C, Patterson RB, Yodice PC. Source: Chest. 2001 December; 120(6): 2101-3. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11742947&dopt=Abstract
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Oculopharyngeal muscular dystrophy in a Japanese family with a short GCG expansion (GCG)(11) in PABP2 gene. Author(s): Nagashima T, Kato H, Kase M, Maguchi S, Mizutani Y, Matsuda K, Chuma T, Mano Y, Goto Y, Minami N, Nonaka I, Nagashima K. Source: Neuromuscular Disorders : Nmd. 2000 March; 10(3): 173-7. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10734263&dopt=Abstract
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Oculopharyngeal muscular dystrophy in a northern German family linked to chromosome 14q, and presenting carnitine deficiency. Author(s): Porschke H, Kress W, Reichmann H, Goebel HH, Grimm T. Source: Neuromuscular Disorders : Nmd. 1997 October; 7 Suppl 1: S57-62. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=9392018&dopt=Abstract
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Oculopharyngeal muscular dystrophy in France. Author(s): Fardeau M, Tome FM. Source: Neuromuscular Disorders : Nmd. 1997 October; 7 Suppl 1: S30-3. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=9392012&dopt=Abstract
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Oculopharyngeal muscular dystrophy in Hispanic New Mexicans. Author(s): Becher MW, Morrison L, Davis LE, Maki WC, King MK, Bicknell JM, Reinert BL, Bartolo C, Bear DG. Source: Jama : the Journal of the American Medical Association. 2001 November 21; 286(19): 2437-40. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11712939&dopt=Abstract
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Oculopharyngeal muscular dystrophy in Italy. Author(s): Meola G, Sansone V, Rotondo G, Tome FM, Bouchard JP. Source: Neuromuscular Disorders : Nmd. 1997 October; 7 Suppl 1: S53-6. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=9392017&dopt=Abstract
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Oculopharyngeal muscular dystrophy in Japan. Author(s): Uyama E, Nohira O, Tome FM, Chateau D, Tokunaga M, Ando M, Maki M, Okabe T, Uchino M. Source: Neuromuscular Disorders : Nmd. 1997 October; 7 Suppl 1: S41-9. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=9392015&dopt=Abstract
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Oculopharyngeal muscular dystrophy in Norway. Survey of a large Norwegian family. Author(s): Salvesen R, Brautaset NJ. Source: Acta Neurologica Scandinavica. 1996 April; 93(4): 281-5. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=8739439&dopt=Abstract
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Oculopharyngeal muscular dystrophy in two unrelated Japanese families. Author(s): Uyama E, Nohira O, Chateau D, Tokunaga M, Uchino M, Okabe T, Ando M, Tome FM. Source: Neurology. 1996 March; 46(3): 773-8. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=8618681&dopt=Abstract
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Oculopharyngeal muscular dystrophy in Uruguay. Author(s): Medici M, Pizzarossa C, Skuk D, Yorio D, Emmanuelli G, Mesa R. Source: Neuromuscular Disorders : Nmd. 1997 October; 7 Suppl 1: S50-2. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=9392016&dopt=Abstract
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Oculopharyngeal muscular dystrophy, other ocular myopathies, and progressive external ophthalmoplegia. Author(s): Rowland LP, Hirano M, DiMauro S, Schon EA. Source: Neuromuscular Disorders : Nmd. 1997 October; 7 Suppl 1: S15-21. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=9392010&dopt=Abstract
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Oculopharyngeal muscular dystrophy. Author(s): Sarkar AK, Biswas SK, Ghosh AK, Mitra P, Ghosh SK, Mathew J. Source: Indian J Pediatr. 1995 July-August; 62(4): 496-8. No Abstract Available. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10829913&dopt=Abstract
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Oculopharyngeal muscular dystrophy. Author(s): Brais B, Rouleau GA, Bouchard JP, Fardeau M, Tome FM. Source: Seminars in Neurology. 1999; 19(1): 59-66. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10711989&dopt=Abstract
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Oculopharyngeal muscular dystrophy: clinical and CT findings. Author(s): Bilgen C, Bilgen IG, Sener RN. Source: Computerized Medical Imaging and Graphics : the Official Journal of the Computerized Medical Imaging Society. 2001 November-December; 25(6): 527-9. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11679216&dopt=Abstract
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Oculopharyngeal muscular dystrophy: clinical and morphological follow-up study reveals mitochondrial alterations and unique nuclear inclusions in a severe autosomal recessive type. Author(s): Schroder JM, Krabbe B, Weis J. Source: Neuropathology and Applied Neurobiology. 1995 February; 21(1): 68-73. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=7770123&dopt=Abstract
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Oculopharyngeal muscular dystrophy: non-French-Canadian pedigrees. Author(s): Creel GB, Giuliani MJ, Lacomis D, Holbach SM. Source: Muscle & Nerve. 1998 June; 21(6): 816-8. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=9585341&dopt=Abstract
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Oculopharyngeal muscular dystrophy: phenotypic and genotypic studies in a UK population. Author(s): Hill ME, Creed GA, McMullan TF, Tyers AG, Hilton-Jones D, Robinson DO, Hammans SR. Source: Brain; a Journal of Neurology. 2001 March; 124(Pt 3): 522-6. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11222452&dopt=Abstract
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Oculopharyngodistal myopathy is genetically heterogeneous and most cases are distinct from oculopharyngeal muscular dystrophy. Author(s): Minami N, Ikezoe K, Kuroda H, Nakabayashi H, Satoyoshi E, Nonaka I. Source: Neuromuscular Disorders : Nmd. 2001 November; 11(8): 699-702. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11595511&dopt=Abstract
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Oligonucleotides against a splicing enhancer sequence led to dystrophin production in muscle cells from a Duchenne muscular dystrophy patient. Author(s): Takeshima Y, Wada H, Yagi M, Ishikawa Y, Ishikawa Y, Minami R, Nakamura H, Matsuo M. Source: Brain & Development. 2001 December; 23(8): 788-90. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11720794&dopt=Abstract
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On the origin of deletions and point mutations in Duchenne muscular dystrophy: most deletions arise in oogenesis and most point mutations result from events in spermatogenesis. Author(s): Grimm T, Meng G, Liechti-Gallati S, Bettecken T, Muller CR, Muller B. Source: Journal of Medical Genetics. 1994 March; 31(3): 183-6. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=8014964&dopt=Abstract
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On the significance of retinal vascular disease and hearing loss in facioscapulohumeral muscular dystrophy. Author(s): Padberg GW, Brouwer OF, de Keizer RJ, Dijkman G, Wijmenga C, Grote JJ, Frants RR. Source: Muscle & Nerve. 1995; 2: S73-80. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=7739630&dopt=Abstract
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One base deletion in the cysteine-rich domain of the dystrophin gene in Duchenne muscular dystrophy patients. Author(s): Tsukamoto H, Inui K, Matsuoka T, Yanagihara I, Fukushima H, Okada S. Source: Human Molecular Genetics. 1994 June; 3(6): 995-6. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=7951251&dopt=Abstract
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Oral exfoliative cytology for the non-invasive diagnosis in X-linked Emery-Dreifuss muscular dystrophy patients and carriers. Author(s): Sabatelli P, Squarzoni S, Petrini S, Capanni C, Ognibene A, Cartegni L, Cobianchi F, Merlini L, Toniolo D, Maraldi NM. Source: Neuromuscular Disorders : Nmd. 1998 April; 8(2): 67-71. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=9608558&dopt=Abstract
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Oral glutamine slows down whole body protein breakdown in Duchenne muscular dystrophy. Author(s): Hankard RG, Hammond D, Haymond MW, Darmaun D. Source: Pediatric Research. 1998 February; 43(2): 222-6. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=9475288&dopt=Abstract
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Orthopedic approaches for the treatment of lower extremity contractures in the Duchenne muscular dystrophy patient in the United States and Canada. Author(s): Hsu JD. Source: Seminars in Neurology. 1995 March; 15(1): 6-8. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=7638460&dopt=Abstract
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Oxidative damage to muscle protein in Duchenne muscular dystrophy. Author(s): Haycock JW, MacNeil S, Jones P, Harris JB, Mantle D. Source: Neuroreport. 1996 December 20; 8(1): 357-61. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=9051810&dopt=Abstract
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Oxidative stress in the brain of Fukuyama type congenital muscular dystrophy: immunohistochemical study on astrocytes. Author(s): Yamamoto T, Shibata N, Kobayashi M, Saito K, Osawa M. Source: Journal of Child Neurology. 2002 November; 17(11): 793-9. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12585716&dopt=Abstract
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P300 and respiratory findings in myotonic muscular dystrophy. Author(s): Oliveri M, Fierro B, Lo Presti R, Brighina F, La Bua V, Caimi G. Source: Funct Neurol. 1999 July-September; 14(3): 149-54. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10568215&dopt=Abstract
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PABP2 polyalanine tract expansion causes intranuclear inclusions in oculopharyngeal muscular dystrophy. Author(s): Shanmugam V, Dion P, Rochefort D, Laganiere J, Brais B, Rouleau GA. Source: Annals of Neurology. 2000 November; 48(5): 798-802. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11079546&dopt=Abstract
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Paradoxical weight loss with extra energy expenditure at brown adipose tissue in adolescent patients with Duchenne muscular dystrophy. Author(s): Satomura S, Yokota I, Tatara K, Naito E, Ito M, Kuroda Y. Source: Metabolism: Clinical and Experimental. 2001 October; 50(10): 1181-5. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11586490&dopt=Abstract
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Paraffin wax embedded muscle is suitable for the diagnosis of muscular dystrophy. Author(s): Sewry CA. Source: Journal of Clinical Pathology. 2002 August; 55(8): 639; Author Reply 639. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12147670&dopt=Abstract
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Pathological analysis of muscle hypertrophy and degeneration in muscular dystrophy in gamma-sarcoglycan-deficient mice. Author(s): Sasaoka T, Imamura M, Araishi K, Noguchi S, Mizuno Y, Takagoshi N, Hama H, Wakabayashi-Takai E, Yoshimoto-Matsuda Y, Nonaka I, Kaneko K, Yoshida M, Ozawa E. Source: Neuromuscular Disorders : Nmd. 2003 March; 13(3): 193-206. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12609501&dopt=Abstract
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Pathological case of the month. Progressive hypertonic muscular dystrophy. Author(s): Cawkwell GD, Lacson AG, Kriseman T. Source: Archives of Pediatrics & Adolescent Medicine. 2001 July; 155(7): 853-4. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11434859&dopt=Abstract
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Pathophysiology of limb girdle muscular dystrophy type 2A: hypothesis and new insights into the IkappaBalpha/NF-kappaB survival pathway in skeletal muscle. Author(s): Baghdiguian S, Richard I, Martin M, Coopman P, Beckmann JS, Mangeat P, Lefranc G. Source: Journal of Molecular Medicine (Berlin, Germany). 2001 June; 79(5-6): 254-61. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11485017&dopt=Abstract
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Patterns of deletions and the distribution of breakpoints in the dystrophin gene in Czech patients with Duchenne and Becker muscular dystrophy (statistical comparison with results from several other countries). Author(s): Hrdlicka I, Zadina J, Krejci R, Srbova A, Kucerova M. Source: Folia Biol (Praha). 2001; 47(3): 81-7. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11409318&dopt=Abstract
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PCR based mutation screening of the laminin alpha2 chain gene (LAMA2): application to prenatal diagnosis and search for founder effects in congenital muscular dystrophy. Author(s): Guicheney P, Vignier N, Zhang X, He Y, Cruaud C, Frey V, Helbling-Leclerc A, Richard P, Estournet B, Merlini L, Topaloglu H, Mora M, Harpey JP, Haenggeli CA, Barois A, Hainque B, Schwartz K, Tome FM, Fardeau M, Tryggvason K. Source: Journal of Medical Genetics. 1998 March; 35(3): 211-7. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=9541105&dopt=Abstract
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Pelvic obliquity after fusion of the spine in Duchenne muscular dystrophy. Author(s): Alman BA, Kim HK. Source: The Journal of Bone and Joint Surgery. British Volume. 1999 September; 81(5): 821-4. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10530843&dopt=Abstract
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Pelvic or lumbar fixation for the surgical management of scoliosis in duchenne muscular dystrophy. Author(s): Sengupta DK, Mehdian SH, McConnell JR, Eisenstein SM, Webb JK. Source: Spine. 2002 September 15; 27(18): 2072-9. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12634572&dopt=Abstract
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Persistent hypertransaminasemia as the presenting findings of muscular dystrophy in childhood. Author(s): Lin YC, Lee WT, Huang SF, Young C, Wang PJ, Shen YZ. Source: Acta Paediatr Taiwan. 1999 November-December; 40(6): 424-9. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10927957&dopt=Abstract
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Perturbation in dystrophin-associated glycoprotein complex in a boy with Becker muscular dystrophy. Author(s): Rivier F, Echenne B, Chaix Y, Robert A, Delisle MB, Calvas P, Mornet D. Source: Brain & Development. 2000 January; 22(1): 65-8. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10761838&dopt=Abstract
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Pharmacological strategies for muscular dystrophy. Author(s): Khurana TS, Davies KE. Source: Nature Reviews. Drug Discovery. 2003 May; 2(5): 379-90. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12750741&dopt=Abstract
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Phase I clinical trial utilizing gene therapy for limb girdle muscular dystrophy: alpha, beta-, gamma-, or delta-sarcoglycan gene delivered with intramuscular instillations of adeno-associated vectors. Author(s): Stedman H, Wilson JM, Finke R, Kleckner AL, Mendell J. Source: Human Gene Therapy. 2000 March 20; 11(5): 777-90. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10757357&dopt=Abstract
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Phenotypic behavior of caveolin-3 mutations that cause autosomal dominant limb girdle muscular dystrophy (LGMD-1C). Retention of LGMD-1C caveolin-3 mutants within the golgi complex. Author(s): Galbiati F, Volonte D, Minetti C, Chu JB, Lisanti MP. Source: The Journal of Biological Chemistry. 1999 September 3; 274(36): 25632-41. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10464299&dopt=Abstract
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Physical capacity in non-ambulatory people with Duchenne muscular dystrophy or spinal muscular atrophy: a longitudinal study. Author(s): Steffensen BF, Lyager S, Werge B, Rahbek J, Mattsson E. Source: Developmental Medicine and Child Neurology. 2002 September; 44(9): 623-32. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12227617&dopt=Abstract
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Physiotherapy in muscular dystrophy. Author(s): Kroksmark AK. Source: Scand J Rehabil Med Suppl. 1999; 39: 65-8. Review. No Abstract Available. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10370976&dopt=Abstract
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Pilot trial of albuterol in facioscapulohumeral muscular dystrophy. FSH-DY Group. Author(s): Kissel JT, McDermott MP, Natarajan R, Mendell JR, Pandya S, King WM, Griggs RC, Tawil R. Source: Neurology. 1998 May; 50(5): 1402-6. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=9595995&dopt=Abstract
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Plasma levels of natriuretic peptide and echocardiographic parameters in patients with Duchenne's progressive muscular dystrophy. Author(s): Mori K, Manabe T, Nii M, Hayabuchi Y, Kuroda Y, Tatara K. Source: Pediatric Cardiology. 2002 March-April; 23(2): 160-6. Epub 2002 February 19. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11889527&dopt=Abstract
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Platelet function deficiency in Duchenne muscular dystrophy. Author(s): Forst J, Forst R, Leithe H, Maurin N. Source: Neuromuscular Disorders : Nmd. 1998 February; 8(1): 46-9. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=9565990&dopt=Abstract
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Point mutation and polymorphism in Duchenne/Becker muscular dystrophy (D/BMD) patients. Author(s): Chaturvedi LS, Mukherjee M, Srivastava S, Mittal RD, Mittal B. Source: Experimental & Molecular Medicine. 2001 December 31; 33(4): 251-6. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11795488&dopt=Abstract
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Postoperative malnutrition in Duchenne muscular dystrophy. Author(s): Iannaccone ST, Owens H, Scott J, Teitell B. Source: Journal of Child Neurology. 2003 January; 18(1): 17-20. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12661933&dopt=Abstract
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Practical problems and management of seating through the clinical stages of Duchenne's muscular dystrophy. Author(s): Liu M, Mineo K, Hanayama K, Fujiwara T, Chino N. Source: Archives of Physical Medicine and Rehabilitation. 2003 June; 84(6): 818-24. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12808532&dopt=Abstract
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Prediction of progression of spinal deformity in Duchenne muscular dystrophy: a preliminary report. Author(s): Yamashita T, Kanaya K, Kawaguchi S, Murakami T, Yokogushi K. Source: Spine. 2001 June 1; 26(11): E223-6. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11389405&dopt=Abstract
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Predictive factors of cessation of ambulation in patients with Duchenne muscular dystrophy. Author(s): Bakker JP, De Groot IJ, Beelen A, Lankhorst GJ. Source: American Journal of Physical Medicine & Rehabilitation / Association of Academic Physiatrists. 2002 December; 81(12): 906-12. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12447089&dopt=Abstract
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Prednisolone in Duchenne muscular dystrophy. Author(s): Rahman MM, Hannan MA, Mondol BA, Bhoumick NB, Haque A. Source: Bangladesh Med Res Counc Bull. 2001 April; 27(1): 38-42. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11692899&dopt=Abstract
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Prednisone therapy in Becker's muscular dystrophy. Author(s): Johnsen SD. Source: Journal of Child Neurology. 2001 November; 16(11): 870-1. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11732779&dopt=Abstract
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Prenatal diagnosis for facioscapulohumeral muscular dystrophy (FSHD). Author(s): Upadhyaya M, MacDonald M, Ravine D. Source: Prenatal Diagnosis. 1999 October; 19(10): 959-65. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10521823&dopt=Abstract
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Prenatal diagnosis in a family affected with beta-sarcoglycan muscular dystrophy. Author(s): Pegoraro E, Fanin M, Angelini C, Hoffman EP. Source: Neuromuscular Disorders : Nmd. 1999 July; 9(5): 323-5. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10407854&dopt=Abstract
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Prenatal diagnosis of Duchenne muscular dystrophy. Author(s): Maheshwari M, Vijaya R, Kabra M, Arora S, Shastri SS, Deka D, Kriplani A, Menon PS. Source: Natl Med J India. 2000 May-June; 13(3): 129-31. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11558111&dopt=Abstract
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Prenatal diagnosis of Fukuyama type congenital muscular dystrophy in eight Japanese families by haplotype analysis using new markers closest to the gene. Author(s): Saito K, Kondo-Iida E, Kawakita Y, Juan D, Ikeya K, Osawa M, Fukuyama Y, Toda T, Nakabayashi M, Yamamoto T, Kobayashi M. Source: American Journal of Medical Genetics. 1998 May 26; 77(4): 310-6. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=9600742&dopt=Abstract
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Prenatal diagnosis of Fukuyama-type congenital muscular dystrophy by microsatellite analysis. Author(s): Takai Y, Tsutsumi O, Harada I, Fujii T, Kashima T, Kobayashi K, Toda T, Taketani Y. Source: Human Reproduction (Oxford, England). 1998 February; 13(2): 320-3. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=9557830&dopt=Abstract
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Prenatal diagnosis of limb-girdle muscular dystrophy type 2A. Author(s): Restagno G, Romero N, Richard I, Beckmann JS, Pagliano M, Ferrone M, Carbonara A, Merlini L. Source: Neuromuscular Disorders : Nmd. 1996 May; 6(3): 173-6. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=8784805&dopt=Abstract
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Prevalence and patterns of cardiac involvement in duchenne muscular dystrophy. Author(s): Ahuja R, Kalra V, Saxena A, Dua T. Source: Indian Pediatrics. 2000 November; 37(11): 1246-51. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11086308&dopt=Abstract
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Prevention of pulmonary morbidity for patients with Duchenne muscular dystrophy. Author(s): Bach JR, Ishikawa Y, Kim H. Source: Chest. 1997 October; 112(4): 1024-8. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=9377912&dopt=Abstract
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Problem-focused coping and satisfaction with activities of daily living in individuals with muscular dystrophy and postpolio syndrome. Author(s): Natterlund B, Ahlstrom G. Source: Scandinavian Journal of Caring Sciences. 1999; 13(1): 26-32. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10476191&dopt=Abstract
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Problems and solutions in the rehabilitation of patients with progressive muscular dystrophy. Author(s): Kakulas BA. Source: Scand J Rehabil Med Suppl. 1999; 39: 23-37. Review. No Abstract Available. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10370970&dopt=Abstract
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Proceedings of the 27th ENMC sponsored workshop on congenital muscular dystrophy. 22-24 April 1994, The Netherlands. Author(s): Dubowitz V, Fardeau M. Source: Neuromuscular Disorders : Nmd. 1995 May; 5(3): 253-8. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10712013&dopt=Abstract
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Process measures and patient/parent evaluation of surgical management of spinal deformities in patients with progressive flaccid neuromuscular scoliosis (Duchenne's muscular dystrophy and spinal muscular atrophy). Author(s): Bridwell KH, Baldus C, Iffrig TM, Lenke LG, Blanke K. Source: Spine. 1999 July 1; 24(13): 1300-9. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10404571&dopt=Abstract
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Profile of electrocardiographic changes in Duchenne muscular dystrophy. Author(s): Bhattacharyya KB, Basu N, Ray TN, Maity B. Source: J Indian Med Assoc. 1997 February; 95(2): 40-2, 47. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=9357240&dopt=Abstract
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Profound misregulation of muscle-specific gene expression in facioscapulohumeral muscular dystrophy. Author(s): Tupler R, Perini G, Pellegrino MA, Green MR. Source: Proceedings of the National Academy of Sciences of the United States of America. 1999 October 26; 96(22): 12650-4. Erratum In: Proc Natl Acad Sci U S a 2000 February 29; 97(5): 2397. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10535977&dopt=Abstract
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Prognostic value of electrocardiograms, ventricular late potentials, ventricular arrhythmias, and left ventricular systolic dysfunction in patients with Duchenne muscular dystrophy. Author(s): Corrado G, Lissoni A, Beretta S, Terenghi L, Tadeo G, Foglia-Manzillo G, Tagliagambe LM, Spata M, Santarone M. Source: The American Journal of Cardiology. 2002 April 1; 89(7): 838-41. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11909570&dopt=Abstract
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Progress in gene therapy for Duchenne muscular dystrophy. Author(s): Clemens PR, Duncan FJ. Source: Curr Neurol Neurosci Rep. 2001 January; 1(1): 89-96. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11898504&dopt=Abstract
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Progress in the molecular diagnosis of facioscapulohumeral muscular dystrophy and correlation between the number of KpnI repeats at the 4q35 locus and clinical phenotype. Author(s): Ricci E, Galluzzi G, Deidda G, Cacurri S, Colantoni L, Merico B, Piazzo N, Servidei S, Vigneti E, Pasceri V, Silvestri G, Mirabella M, Mangiola F, Tonali P, Felicetti L. Source: Annals of Neurology. 1999 June; 45(6): 751-7. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10360767&dopt=Abstract
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Progress in understanding the pathogenesis of oculopharyngeal muscular dystrophy. Author(s): Fan X, Rouleau GA. Source: The Canadian Journal of Neurological Sciences. Le Journal Canadien Des Sciences Neurologiques. 2003 February; 30(1): 8-14. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12619777&dopt=Abstract
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Progress toward gene therapy of Duchenne muscular dystrophy. Author(s): Hartigan-O'Connor D, Chamberlain JS. Source: Seminars in Neurology. 1999; 19(3): 323-32. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12194388&dopt=Abstract
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Progress towards gene therapy for Duchenne muscular dystrophy. Author(s): Hauser MA, Chamberlain JS. Source: The Journal of Endocrinology. 1996 June; 149(3): 373-8. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=8691095&dopt=Abstract
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Properties of lamin A mutants found in Emery-Dreifuss muscular dystrophy, cardiomyopathy and Dunnigan-type partial lipodystrophy. Author(s): Ostlund C, Bonne G, Schwartz K, Worman HJ. Source: Journal of Cell Science. 2001 December; 114(Pt 24): 4435-45. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11792809&dopt=Abstract
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Proteasome expression in the skeletal muscles of patients with muscular dystrophy. Author(s): Kumamoto T, Fujimoto S, Ito T, Horinouchi H, Ueyama H, Tsuda T. Source: Acta Neuropathologica. 2000 December; 100(6): 595-602. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11078210&dopt=Abstract
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Protein and gene analyses of dysferlinopathy in a large group of Japanese muscular dystrophy patients. Author(s): Tagawa K, Ogawa M, Kawabe K, Yamanaka G, Matsumura T, Goto K, Nonaka I, Nishino I, Hayashi YK. Source: Journal of the Neurological Sciences. 2003 July 15; 211(1-2): 23-8. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12767493&dopt=Abstract
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Pseudoexon activation in the DMD gene as a novel mechanism for Becker muscular dystrophy. Author(s): Tuffery-Giraud S, Saquet C, Chambert S, Claustres M. Source: Human Mutation. 2003 June; 21(6): 608-14. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12754707&dopt=Abstract
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Pseudohypertrophic muscular dystrophy with pulmonary valve stenosis: an unusual association. Author(s): Xie CH, Xia CS. Source: Pediatric Cardiology. 2002 March-April; 23(2): 216-7. Epub 2002 February 19. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11889540&dopt=Abstract
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Pseudohypertrophy of the temporalis muscle in Xp21 muscular dystrophy. Author(s): Richards P, Saywell WR, Heywood P. Source: Developmental Medicine and Child Neurology. 2000 November; 42(11): 786-7. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11104355&dopt=Abstract
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Pseudo-metabolic presentation in a Duchenne muscular dystrophy symptomatic carrier with 'de novo' duplication of dystrophin gene. Author(s): Romero NB, De Lonlay P, Llense S, Leturcq F, Touati G, Urtizberea JA, Saudubray JM, Munnich A, Kaplan JC, Recan D. Source: Neuromuscular Disorders : Nmd. 2001 July; 11(5): 494-8. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11404124&dopt=Abstract
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Pulmonary manifestations of neuromuscular disease with special reference to Duchenne muscular dystrophy and spinal muscular atrophy. Author(s): Gozal D. Source: Pediatric Pulmonology. 2000 February; 29(2): 141-50. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10639205&dopt=Abstract
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Pulse field gel electrophoresis for the detection of facioscapulohumeral muscular dystrophy gene rearrangements. Author(s): Felicetti L, Galluzzi G. Source: Methods in Molecular Biology (Clifton, N.J.). 2003; 217: 153-64. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12491930&dopt=Abstract
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QT dispersion in patients with Duchenne-type progressive muscular dystrophy. Author(s): Yotsukura M, Yamamoto A, Kajiwara T, Nishimura T, Sakata K, Ishihara T, Ishikawa K. Source: American Heart Journal. 1999 April; 137(4 Pt 1): 672-7. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10097228&dopt=Abstract
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Quantitative and qualitative alterations of dystrophin are expressed in muscle cell cultures of Xp21 muscular dystrophy patients (Duchenne and Becker type). Author(s): Mongini T, Doriguzzi C, Palmucci L, Chiado-Piat L. Source: European Journal of Clinical Investigation. 1996 April; 26(4): 322-4. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=8732491&dopt=Abstract
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Quantitative assessment of calf circumference in Duchenne muscular dystrophy patients. Author(s): Beenakker EA, de Vries J, Fock JM, van Tol M, Brouwer OF, Maurits NM, van der Hoeven JH. Source: Neuromuscular Disorders : Nmd. 2002 October; 12(7-8): 639-42. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12207931&dopt=Abstract
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Quantitative ELISA for platelet m-calpain: a phenotypic index for detection of carriers of Duchenne muscular dystrophy. Author(s): Hussain T, Kumar DV, Sundaram C, Mohandas S, Anandaraj MP. Source: Clinica Chimica Acta; International Journal of Clinical Chemistry. 1998 January 12; 269(1): 13-20. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=9498100&dopt=Abstract
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Quantitative MR evaluation of body composition in patients with Duchenne muscular dystrophy. Author(s): Pichiecchio A, Uggetti C, Egitto MG, Berardinelli A, Orcesi S, Gorni KO, Zanardi C, Tagliabue A. Source: European Radiology. 2002 November; 12(11): 2704-9. Epub 2002 May 08. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12386760&dopt=Abstract
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Quantitative MR relaxometry study of muscle composition and function in Duchenne muscular dystrophy. Author(s): Huang Y, Majumdar S, Genant HK, Chan WP, Sharma KR, Yu P, Mynhier M, Miller RG. Source: Journal of Magnetic Resonance Imaging : Jmri. 1994 January-February; 4(1): 5964. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=8148557&dopt=Abstract
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rAAV vector-mediated sarcogylcan gene transfer in a hamster model for limb girdle muscular dystrophy. Author(s): Li J, Dressman D, Tsao YP, Sakamoto A, Hoffman EP, Xiao X. Source: Gene Therapy. 1999 January; 6(1): 74-82. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10341878&dopt=Abstract
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Randomised trial of preventive nasal ventilation in Duchenne muscular dystrophy. French Multicentre Cooperative Group on Home Mechanical Ventilation Assistance in Duchenne de Boulogne Muscular Dystrophy. Author(s): Raphael JC, Chevret S, Chastang C, Bouvet F. Source: Lancet. 1994 June 25; 343(8913): 1600-4. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=7911921&dopt=Abstract
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Rapacuronium administration to two children with Duchenne's muscular dystrophy. Author(s): Frankowski GA, Johnson JO, Tobias JD. Source: Anesthesia and Analgesia. 2000 July; 91(1): 27-8. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10866881&dopt=Abstract
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Rapid DNA haplotyping using a multiplex heteroduplex approach: application to Duchenne muscular dystrophy carrier testing. Author(s): Prior TW, Wenger GD, Papp AC, Snyder PJ, Sedra MS, Bartolo C, Moore JW, Highsmith WE. Source: Human Mutation. 1995; 5(3): 263-8. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=7599638&dopt=Abstract
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Rare combination of Becker muscular dystrophy and Klinefelter's syndrome in one patient. Author(s): Zeitoun O, Ketelsen UP, Wolff G, Muller CR, Korinthenberg R. Source: Brain & Development. 1997 July; 19(5): 359-61. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=9253490&dopt=Abstract
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Reading ability and processing in Duchenne muscular dystrophy and spinal muscular atrophy. Author(s): Billard C, Gillet P, Barthez M, Hommet C, Bertrand P. Source: Developmental Medicine and Child Neurology. 1998 January; 40(1): 12-20. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=9459212&dopt=Abstract
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Readjusting the localization of merosin (laminin alpha 2-chain) deficient congenital muscular dystrophy locus on chromosome 6q2. Author(s): Helbling-Leclerc A, Topaloglu H, Tome FM, Sewry C, Gyapay G, Naom I, Muntoni F, Dubowitz V, Barois A, Estournet B, et al. Source: Comptes Rendus De L'academie Des Sciences. Serie Iii, Sciences De La Vie. 1995 December; 318(12): 1245-52. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=8745640&dopt=Abstract
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Reasons to be cheerful. Genetic diagnosis and therapy are offering hope to people with muscular dystrophy. Author(s): Bird C. Source: Nurs Times. 2001 August 2-8; 97(31): 25. No Abstract Available. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11957528&dopt=Abstract
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Recent studies on oculopharyngeal muscular dystrophy in Quebec. Author(s): Bouchard JP, Brais B, Brunet D, Gould PV, Rouleau GA. Source: Neuromuscular Disorders : Nmd. 1997 October; 7 Suppl 1: S22-9. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=9392011&dopt=Abstract
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Reciprocal expression of dystrophin and utrophin in muscles of Duchenne muscular dystrophy patients, female DMD-carriers and control subjects. Author(s): Mizuno Y, Nonaka I, Hirai S, Ozawa E. Source: Journal of the Neurological Sciences. 1993 October; 119(1): 43-52. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=8246010&dopt=Abstract
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Recombinant cryptic human fibronectinase cleaves actin and myosin: substrate specificity and possible role in muscular dystrophy. Author(s): Schnepel J, Unger J, Tschesche H. Source: Biological Chemistry. 2001 December; 382(12): 1707-14. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11843184&dopt=Abstract
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Recurrent pneumothoraces associated with nocturnal noninvasive ventilation in a patient with muscular dystrophy. Author(s): Choo-Kang LR, Ogunlesi FO, McGrath-Morrow SA, Crawford TO, Marcus CL. Source: Pediatric Pulmonology. 2002 July; 34(1): 73-8. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12112801&dopt=Abstract
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Reduced aquaporin 4 expression in the muscle plasma membrane of patients with Duchenne muscular dystrophy. Author(s): Wakayama Y, Jimi T, Inoue M, Kojima H, Murahashi M, Kumagai T, Yamashita S, Hara H, Shibuya S. Source: Archives of Neurology. 2002 March; 59(3): 431-7. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11890849&dopt=Abstract
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Reduced cytosolic acidification during exercise suggests defective glycolytic activity in skeletal muscle of patients with Becker muscular dystrophy. An in vivo 31P magnetic resonance spectroscopy study. Author(s): Lodi R, Kemp GJ, Muntoni F, Thompson CH, Rae C, Taylor J, Styles P, Taylor DJ. Source: Brain; a Journal of Neurology. 1999 January; 122 ( Pt 1): 121-30. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10050900&dopt=Abstract
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Reducing iliotibial band contractures in patients with muscular dystrophy using custom dry floatation cushions. Author(s): Wong CK, Wade CK. Source: Archives of Physical Medicine and Rehabilitation. 1995 July; 76(7): 695-700. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=7605194&dopt=Abstract
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Refined genetic location of the chromosome 2p-linked progressive muscular dystrophy gene. Author(s): Illarioshkin SN, Ivanova-Smolenskaya IA, Tanaka H, Poleshchuk VV, Markova ED, Tsuji S. Source: Genomics. 1997 June 1; 42(2): 345-8. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=9192858&dopt=Abstract
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Refined mapping of a gene responsible for Fukuyama-type congenital muscular dystrophy: evidence for strong linkage disequilibrium. Author(s): Toda T, Ikegawa S, Okui K, Kondo E, Saito K, Fukuyama Y, Yoshioka M, Kumagai T, Suzumori K, Kanazawa I, et al. Source: American Journal of Human Genetics. 1994 November; 55(5): 946-50. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=7977357&dopt=Abstract
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Refinement of the laminin alpha2 chain locus to human chromosome 6q2 in severe and mild merosin deficient congenital muscular dystrophy. Author(s): Naom IS, D'Alessandro M, Topaloglu H, Sewry C, Ferlini A, Helbling-Leclerc A, Guicheney P, Weissenbach J, Schwartz K, Bushby K, Philpot J, Dubowitz V, Muntoni F. Source: Journal of Medical Genetics. 1997 February; 34(2): 99-104. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=9039983&dopt=Abstract
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Relationship between utrophin and regenerating muscle fibers in duchenne muscular dystrophy. Author(s): Shim JY, Kim TS. Source: Yonsei Medical Journal. 2003 February; 44(1): 15-23. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12619170&dopt=Abstract
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Relatively low proportion of dystrophin gene deletions in Israeli Duchenne and Becker muscular dystrophy patients. Author(s): Shomrat R, Gluck E, Legum C, Shiloh Y. Source: American Journal of Medical Genetics. 1994 February 15; 49(4): 369-73. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=8160727&dopt=Abstract
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Remission of clinical signs in early duchenne muscular dystrophy on intermittent low-dosage prednisolone therapy. Author(s): Dubowitz V, Kinali M, Main M, Mercuri E, Muntoni F. Source: European Journal of Paediatric Neurology : Ejpn : Official Journal of the European Paediatric Neurology Society. 2002; 6(3): 153-9. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12363102&dopt=Abstract
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Removal of dystroglycan causes severe muscular dystrophy in zebrafish embryos. Author(s): Parsons MJ, Campos I, Hirst EM, Stemple DL. Source: Development (Cambridge, England). 2002 July; 129(14): 3505-12. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12091319&dopt=Abstract
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Report of the sixth International Workshop on Facioscapulohumeral Muscular Dystrophy: San Francisco, 11 November 1992; and current guidelines for clinical application of DNA rearrangements at locus D4S810. Muscular Dystrophy Group of America. Author(s): Lunt PW. Source: Neuromuscular Disorders : Nmd. 1994 January; 4(1): 83-6. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=8173356&dopt=Abstract
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Respiratory abdominal muscle recruitment and chest wall motion in myotonic muscular dystrophy. Author(s): Ugalde V, Walsh S, Abresch RT, Bonekat HW, Breslin E. Source: Journal of Applied Physiology (Bethesda, Md. : 1985). 2001 July; 91(1): 395-407. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11408457&dopt=Abstract
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Respiratory concerns in Duchenne muscular dystrophy (DMD). Author(s): Leger P, Leger SS. Source: Pediatr Pulmonol Suppl. 1997; 16: 137-9. Review. No Abstract Available. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=9443242&dopt=Abstract
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Respiratory dysfunction in muscular dystrophy and other myopathies. Author(s): Lynn DJ, Woda RP, Mendell JR. Source: Clinics in Chest Medicine. 1994 December; 15(4): 661-74. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=7867281&dopt=Abstract
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Respiratory function, electrocardiography and quality of life in individuals with muscular dystrophy. Author(s): Ahlstrom G, Gunnarsson LG, Kihlgren A, Arvill A, Sjoden PO. Source: Chest. 1994 July; 106(1): 173-9. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=8020268&dopt=Abstract
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Response to vecuronium in a patient with facioscapulohumeral muscular dystrophy. Author(s): Nitahara K, Sakuragi T, Matsuyama M, Dan K. Source: British Journal of Anaesthesia. 1999 September; 83(3): 499-500. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10655933&dopt=Abstract
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Responses to extracellular ATP of lymphoblastoid cell lines from Duchenne muscular dystrophy patients. Author(s): Ferrari D, Munerati M, Melchiorri L, Hanau S, di Virgilio F, Baricordi OR. Source: The American Journal of Physiology. 1994 October; 267(4 Pt 1): C886-92. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=7524344&dopt=Abstract
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Resting energy expenditure and energy substrate utilization in children with Duchenne muscular dystrophy. Author(s): Hankard R, Gottrand F, Turck D, Carpentier A, Romon M, Farriaux JP. Source: Pediatric Research. 1996 July; 40(1): 29-33. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=8798242&dopt=Abstract
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Restoration of half the normal dystrophin sequence in a double-deletion Duchenne muscular dystrophy family. Author(s): Hoop RC, Russo LS, Riconda DL, Schwartz LS, Hoffman EP. Source: American Journal of Medical Genetics. 1994 February 1; 49(3): 323-7. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=8209894&dopt=Abstract
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Restriction map of a YAC and cosmid contig encompassing the oculopharyngeal muscular dystrophy candidate region on chromosome 14q11.2-q13. Author(s): Xie YG, Rochefort D, Brais B, Howard H, Han FY, Gou LP, Maciel P, The BT, Larsson C, Rouleau GA. Source: Genomics. 1998 September 1; 52(2): 201-4. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=9782086&dopt=Abstract
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Retinal signal transmission in Duchenne muscular dystrophy: evidence for dysfunction in the photoreceptor/depolarizing bipolar cell pathway. Author(s): Fitzgerald KM, Cibis GW, Giambrone SA, Harris DJ. Source: The Journal of Clinical Investigation. 1994 June; 93(6): 2425-30. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=8200977&dopt=Abstract
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Retrograde intubation difficulty in an 18-year-old muscular dystrophy patient. Author(s): van Stralen D, Perkin RM. Source: The American Journal of Emergency Medicine. 1995 January; 13(1): 100-1. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=7832927&dopt=Abstract
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Retroviral vectors for gene therapy of Duchenne muscular dystrophy. Author(s): Fassati A, Bresolin N. Source: Neurological Sciences : Official Journal of the Italian Neurological Society and of the Italian Society of Clinical Neurophysiology. 2000; 21(5 Suppl): S925-7. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11382191&dopt=Abstract
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Revertant fibres: a possible genetic therapy for Duchenne muscular dystrophy? Author(s): Wilton SD, Dye DE, Blechynden LM, Laing NG. Source: Neuromuscular Disorders : Nmd. 1997 July; 7(5): 329-35. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=9267847&dopt=Abstract
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Rhabdomyolysis in association with Duchenne's muscular dystrophy. Author(s): Obata R, Yasumi Y, Suzuki A, Nakajima Y, Sato S. Source: Canadian Journal of Anaesthesia = Journal Canadien D'anesthesie. 1999 June; 46(6): 564-6. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10391604&dopt=Abstract
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Rigid internal fixation of the jaws in an adult patient with facio-scapulo-humeral muscular dystrophy: report of a case. Author(s): Marchetti C, Bianchi A, Merlini L, Tonelli P. Source: Journal of Cranio-Maxillo-Facial Surgery : Official Publication of the European Association for Cranio-Maxillo-Facial Surgery. 1997 October; 25(5): 275-8. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=9368864&dopt=Abstract
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Role of apoptosis in Duchenne's muscular dystrophy. Author(s): Serdaroglu A, Gucuyener K, Erdem S, Kose G, Tan E, Okuyaz C. Source: Journal of Child Neurology. 2002 January; 17(1): 66-8. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11913578&dopt=Abstract
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Role of dystrophin isoforms and associated proteins in muscular dystrophy (review). Author(s): Culligan KG, Mackey AJ, Finn DM, Maguire PB, Ohlendieck K. Source: International Journal of Molecular Medicine. 1998 December; 2(6): 639-48. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=9850730&dopt=Abstract
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Row-a-boat phenomenon: respiratory compensation in advanced Duchenne muscular dystrophy. Author(s): Yasuma F, Kato T, Matsuoka Y, Konagaya M. Source: Chest. 2001 June; 119(6): 1836-9. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11399712&dopt=Abstract
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Saccadic eye movements are impaired in Duchenne muscular dystrophy. Author(s): Lui F, Fonda S, Merlini L, Corazza R. Source: Documenta Ophthalmologica. Advances in Ophthalmology. 2001 November; 103(3): 219-28. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11824659&dopt=Abstract
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Sarcoglycanopathies are responsible for 68% of severe autosomal recessive limbgirdle muscular dystrophy in the Brazilian population. Author(s): Vainzof M, Passos-Bueno MR, Pavanello RC, Marie SK, Oliveira AS, Zatz M. Source: Journal of the Neurological Sciences. 1999 March 15; 164(1): 44-9. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10385046&dopt=Abstract
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Sarcoglycanopathies in Dutch patients with autosomal recessive limb girdle muscular dystrophy. Author(s): Ginjaar HB, van der Kooi AJ, Ceelie H, Kneppers AL, van Meegen M, Barth PG, Busch HF, Wokke JH, Anderson LV, Bonnemann CG, Jeanpierre M, Bolhuis PA, Moorman AF, de Visser M, Bakker E, Ommen GJ. Source: Journal of Neurology. 2000 July; 247(7): 524-9. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10993494&dopt=Abstract
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Sarcoglycans in muscular dystrophy. Author(s): Hack AA, Groh ME, McNally EM. Source: Microscopy Research and Technique. 2000 February 1-15; 48(3-4): 167-80. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10679964&dopt=Abstract
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Scapular fixation in muscular dystrophy. Author(s): Mummery CJ, Copeland SA, Rose MR. Source: Cochrane Database Syst Rev. 2003; (3): Cd003278. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12917959&dopt=Abstract
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Scapulothoracic arthrodesis in facioscapulohumeral muscular dystrophy. Author(s): Berne D, Laude F, Laporte C, Fardeau M, Saillant G. Source: Clinical Orthopaedics and Related Research. 2003 April; (409): 106-13. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12671492&dopt=Abstract
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Scoliosis in Duchenne muscular dystrophy. Author(s): Yasuma F, Sakai M. Source: Respiration; International Review of Thoracic Diseases. 1999; 66(5): 463. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10516544&dopt=Abstract
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Screening 25 dystrophin gene exons for deletions in Arab children with Duchenne muscular dystrophy. Author(s): Haider MZ, Bastaki L, Habib Y, Moosa A. Source: Human Heredity. 1998 March-April; 48(2): 61-6. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=9526164&dopt=Abstract
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Secondary calpain3 deficiency in 2q-linked muscular dystrophy: titin is the candidate gene. Author(s): Haravuori H, Vihola A, Straub V, Auranen M, Richard I, Marchand S, Voit T, Labeit S, Somer H, Peltonen L, Beckmann JS, Udd B. Source: Neurology. 2001 April 10; 56(7): 869-77. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11294923&dopt=Abstract
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Secondary reduction in calpain 3 expression in patients with limb girdle muscular dystrophy type 2B and Miyoshi myopathy (primary dysferlinopathies). Author(s): Anderson LV, Harrison RM, Pogue R, Vafiadaki E, Pollitt C, Davison K, Moss JA, Keers S, Pyle A, Shaw PJ, Mahjneh I, Argov Z, Greenberg CR, Wrogemann K, Bertorini T, Goebel HH, Beckmann JS, Bashir R, Bushby KM. Source: Neuromuscular Disorders : Nmd. 2000 December; 10(8): 553-9. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11053681&dopt=Abstract
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Secondary reduction of alpha7B integrin in laminin alpha2 deficient congenital muscular dystrophy supports an additional transmembrane link in skeletal muscle. Author(s): Cohn RD, Mayer U, Saher G, Herrmann R, van der Flier A, Sonnenberg A, Sorokin L, Voit T. Source: Journal of the Neurological Sciences. 1999 March 1; 163(2): 140-52. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10371075&dopt=Abstract
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Selective deficiency of alpha-dystroglycan in Fukuyama-type congenital muscular dystrophy. Author(s): Hayashi YK, Ogawa M, Tagawa K, Noguchi S, Ishihara T, Nonaka I, Arahata K. Source: Neurology. 2001 July 10; 57(1): 115-21. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11445638&dopt=Abstract
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Selective deficits in verbal working memory associated with a known genetic etiology: the neuropsychological profile of duchenne muscular dystrophy. Author(s): Hinton VJ, De Vivo DC, Nereo NE, Goldstein E, Stern Y. Source: Journal of the International Neuropsychological Society : Jins. 2001 January; 7(1): 45-54. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11253841&dopt=Abstract
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Selective muscle involvement on magnetic resonance imaging in autosomal dominant Emery-Dreifuss muscular dystrophy. Author(s): Mercuri E, Counsell S, Allsop J, Jungbluth H, Kinali M, Bonne G, Schwartz K, Bydder G, Dubowitz V, Muntoni F. Source: Neuropediatrics. 2002 February; 33(1): 10-4. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11930270&dopt=Abstract
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Sequence specificity of aminoglycoside-induced stop condon readthrough: potential implications for treatment of Duchenne muscular dystrophy. Author(s): Howard MT, Shirts BH, Petros LM, Flanigan KM, Gesteland RF, Atkins JF. Source: Annals of Neurology. 2000 August; 48(2): 164-9. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10939566&dopt=Abstract
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Serial manual muscle testing in Duchenne muscular dystrophy. Author(s): Kilmer DD, Abresch RT, Fowler WM Jr. Source: Archives of Physical Medicine and Rehabilitation. 1993 November; 74(11): 116871. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=8239956&dopt=Abstract
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Serum antibodies to the deleted dystrophin sequence after cardiac transplantation in a patient with Becker's muscular dystrophy. Author(s): Bittner RE, Shorny S, Streubel B, Hubner C, Voit T, Kress W. Source: The New England Journal of Medicine. 1995 September 14; 333(11): 732-3. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=7637764&dopt=Abstract
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Severe clinical expression in X-linked Emery-Dreifuss muscular dystrophy. Author(s): Hoeltzenbein M, Karow T, Zeller JA, Warzok R, Wulff K, Zschiesche M, Herrmann FH, Grosse-Heitmeyer W, Wehnert MS. Source: Neuromuscular Disorders : Nmd. 1999 May; 9(3): 166-70. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10382910&dopt=Abstract
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Severe congenital muscular dystrophy in a Mexican family with a new nonsense mutation (R2578X) in the laminin alpha-2 gene. Author(s): Coral-Vazquez RM, Rosas-Vargas H, Meza-Espinosa P, Mendoza I, Huicochea JC, Ramon G, Salamanca F. Source: Journal of Human Genetics. 2003; 48(2): 91-5. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12601554&dopt=Abstract
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Severe progressive form of congenital muscular dystrophy with calf pseudohypertrophy, macroglossia and respiratory insufficiency. Author(s): Quijano-Roy S, Galan L, Ferreiro A, Cheliout-Heraut F, Gray F, Fardeau M, Barois A, Guicheney P, Romero NB, Estournet B. Source: Neuromuscular Disorders : Nmd. 2002 June; 12(5): 466-75. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12031620&dopt=Abstract
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Signs and symptoms of Duchenne muscular dystrophy and Becker muscular dystrophy among carriers in The Netherlands: a cohort study. Author(s): Hoogerwaard EM, Bakker E, Ippel PF, Oosterwijk JC, Majoor-Krakauer DF, Leschot NJ, Van Essen AJ, Brunner HG, van der Wouw PA, Wilde AA, de Visser M. Source: Lancet. 1999 June 19; 353(9170): 2116-9. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10382696&dopt=Abstract
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Skeletal muscle metabolism in Duchenne muscular dystrophy (DMD): an in-vitro proton NMR spectroscopy study. Author(s): Sharma U, Atri S, Sharma MC, Sarkar C, Jagannathan NR. Source: Magnetic Resonance Imaging. 2003 February; 21(2): 145-53. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12670601&dopt=Abstract
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Skeletal muscle pathology in autosomal dominant Emery-Dreifuss muscular dystrophy with lamin A/C mutations. Author(s): Sewry CA, Brown SC, Mercuri E, Bonne G, Feng L, Camici G, Morris GE, Muntoni F. Source: Neuropathology and Applied Neurobiology. 2001 August; 27(4): 281-90. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11532159&dopt=Abstract
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Skeletal muscle-specific calpain, p94, and connectin/titin: their physiological functions and relationship to limb-girdle muscular dystrophy type 2A. Author(s): Sorimachi H, Ono Y, Suzuki K. Source: Advances in Experimental Medicine and Biology. 2000; 481: 383-95; Discussion 395-7. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10987085&dopt=Abstract
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Skipping to new gene therapies for muscular dystrophy. Author(s): Tidball JG, Spencer MJ. Source: Nature Medicine. 2003 August; 9(8): 997-8. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12894160&dopt=Abstract
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Sleep-disordered breathing in Duchenne muscular dystrophy: a preliminary study of the role of portable monitoring. Author(s): Kirk VG, Flemons WW, Adams C, Rimmer KP, Montgomery MD. Source: Pediatric Pulmonology. 2000 February; 29(2): 135-40. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10639204&dopt=Abstract
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Social adjustment in adult males affected with progressive muscular dystrophy. Author(s): Eggers S, Zatz M. Source: American Journal of Medical Genetics. 1998 February 7; 81(1): 4-12. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=9514580&dopt=Abstract
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Social deprivation in Duchenne muscular dystrophy: population based study. Author(s): Bushby K, Raybould S, O'Donnell S, Steele JG. Source: Bmj (Clinical Research Ed.). 2001 November 3; 323(7320): 1035-6. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11691762&dopt=Abstract
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Special Centennial Workshop-- 101st ENMC International Workshop: Therapeutic Possibilities in Duchenne Muscular Dystrophy, 30th November-2nd December 2001, Naarden, The Netherlands. Author(s): Dubowitz V. Source: Neuromuscular Disorders : Nmd. 2002 May; 12(4): 421-31. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12062262&dopt=Abstract
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Spinal fusion in Duchenne muscular dystrophy--fixation and fusion to the sacropelvis? Author(s): Mubarak SJ, Morin WD, Leach J. Source: Journal of Pediatric Orthopedics. 1993 November-December; 13(6): 752-7. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=8245201&dopt=Abstract
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Spinal instrumentation for Duchenne's muscular dystrophy: experience of hypotensive anaesthesia to minimise blood loss. Author(s): Fox HJ, Thomas CH, Thompson AG. Source: Journal of Pediatric Orthopedics. 1997 November-December; 17(6): 750-3. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=9591976&dopt=Abstract
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Spinal stabilization in Duchenne muscular dystrophy: principles of treatment and record of 31 operative treated cases. Author(s): Heller KD, Wirtz DC, Siebert CH, Forst R. Source: Journal of Pediatric Orthopaedics. Part B / European Paediatric Orthopaedic Society, Pediatric Orthopaedic Society of North America. 2001 January; 10(1): 18-24. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11269806&dopt=Abstract
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Spin-lock magnetic resonance imaging of muscle in patients with autosomal recessive limb girdle muscular dystrophy. Author(s): Franczak MB, Ulmer JL, Jaradeh S, McDaniel JD, Mark LP, Prost RW. Source: Journal of Neuroimaging : Official Journal of the American Society of Neuroimaging. 2000 April; 10(2): 73-7. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10800259&dopt=Abstract
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Splicing mutation in dysferlin produces limb-girdle muscular dystrophy with inflammation. Author(s): McNally EM, Ly CT, Rosenmann H, Mitrani Rosenbaum S, Jiang W, Anderson LV, Soffer D, Argov Z. Source: American Journal of Medical Genetics. 2000 April 10; 91(4): 305-12. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10766988&dopt=Abstract
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Spontaneous left ventricular hypertrabeculation in dystrophin duplication based Becker's muscular dystrophy. Author(s): Finsterer J, Stollberger C. Source: Herz. 2001 November; 26(7): 477-81. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11765481&dopt=Abstract
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Spontaneous muscular dystrophy caused by a retrotransposal insertion in the mouse laminin alpha2 chain gene. Author(s): Besse S, Allamand V, Vilquin JT, Li Z, Poirier C, Vignier N, Hori H, Guenet JL, Guicheney P. Source: Neuromuscular Disorders : Nmd. 2003 March; 13(3): 216-22. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12609503&dopt=Abstract
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S-protein is expressed in necrotic fibers in Duchenne muscular dystrophy and polymyositis. Author(s): Louboutin JP, Navenot JM, Rouger K, Blanchard D. Source: Muscle & Nerve. 2003 May; 27(5): 575-81. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12707977&dopt=Abstract
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SSCP detection of novel mutations in patients with Emery-Dreifuss muscular dystrophy: definition of a small C-terminal region required for emerin function. Author(s): Nigro V, Bruni P, Ciccodicola A, Politano L, Nigro G, Piluso G, Cappa V, Covone AE, Romeo G, D'Urso M. Source: Human Molecular Genetics. 1995 October; 4(10): 2003-4. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=8595433&dopt=Abstract
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Standards of care in MDA clinics. Muscular Dystrophy Association. Author(s): Bach JR, Chaudhry SS. Source: American Journal of Physical Medicine & Rehabilitation / Association of Academic Physiatrists. 2000 March-April; 79(2): 193-6. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10744195&dopt=Abstract
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Statistically significant differences in the number of CD24 positive muscle fibers and satellite cells between sarcoglycanopathy and age-matched Becker muscular dystrophy patients. Author(s): Higuchi I, Kawai H, Kawajiri M, Fukunaga H, Horikiri T, Niiyama T, Nakagawa M, Arimura K, Osame M. Source: Intern Med. 1999 May; 38(5): 412-5. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10397078&dopt=Abstract
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Strength and functional performance of patients with limb-girdle muscular dystrophy. Author(s): Lue YJ, Chen SS. Source: Kaohsiung J Med Sci. 2000 February; 16(2): 83-90. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10816991&dopt=Abstract
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Structural analysis of emerin, an inner nuclear membrane protein mutated in Xlinked Emery-Dreifuss muscular dystrophy. Author(s): Wolff N, Gilquin B, Courchay K, Callebaut I, Worman HJ, Zinn-Justin S. Source: Febs Letters. 2001 July 20; 501(2-3): 171-6. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11470279&dopt=Abstract
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Structural organization, complete genomic sequences and mutational analyses of the Fukuyama-type congenital muscular dystrophy gene, fukutin. Author(s): Kobayashi K, Sasaki J, Kondo-Iida E, Fukuda Y, Kinoshita M, Sunada Y, Nakamura Y, Toda T. Source: Febs Letters. 2001 February 2; 489(2-3): 192-6. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11165248&dopt=Abstract
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ST-segment displacement in Duchenne muscular dystrophy: myocardial necrosis or apoptosis? Author(s): Politano L, Palladino A, Petretta VR, Mansi L, Passamano L, Nigro G, Comi LI, Nigro G. Source: Acta Myol. 2003 May; 22(1): 5-10. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=13677325&dopt=Abstract
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Substitution of a conserved cysteine-996 in a cysteine-rich motif of the laminin alpha2-chain in congenital muscular dystrophy with partial deficiency of the protein. Author(s): Nissinen M, Helbling-Leclerc A, Zhang X, Evangelista T, Topaloglu H, Cruaud C, Weissenbach J, Fardeau M, Tome FM, Schwartz K, Tryggvason K, Guicheney P. Source: American Journal of Human Genetics. 1996 June; 58(6): 1177-84. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=8651294&dopt=Abstract
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Successful botulinum toxin treatment of dysphagia in oculopharyngeal muscular dystrophy. Author(s): Restivo DA, Marchese Ragona R, Staffieri A, de Grandis D. Source: Gastroenterology. 2000 November; 119(5): 1416. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11185464&dopt=Abstract
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Successful bridge to transplantation in a patient with Becker muscular dystrophyassociated cardiomyopathy. Author(s): Leprince P, Heloire F, Eymard B, Leger P, Duboc D, Pavie A. Source: The Journal of Heart and Lung Transplantation : the Official Publication of the International Society for Heart Transplantation. 2002 July; 21(7): 822-4. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12100911&dopt=Abstract
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Sudden death of a carrier of X-linked Emery-Dreifuss muscular dystrophy. Author(s): Fishbein MC, Siegel RJ, Thompson CE, Hopkins LC. Source: Annals of Internal Medicine. 1993 November 1; 119(9): 900-5. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=8215002&dopt=Abstract
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Surgical correction of blepharoptosis in oculopharyngeal muscular dystrophy. Author(s): Rodrigue D, Molgat YM. Source: Neuromuscular Disorders : Nmd. 1997 October; 7 Suppl 1: S82-4. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=9392022&dopt=Abstract
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Surgical prevention of foot deformity in patients with Duchenne muscular dystrophy. Author(s): Scher DM, Mubarak SJ. Source: Journal of Pediatric Orthopedics. 2002 May-June; 22(3): 384-91. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11961461&dopt=Abstract
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Surgical prevention of foot deformity in patients with Duchenne muscular dystrophy. Author(s): Wright JG. Source: Journal of Pediatric Orthopedics. 2003 May-June; 23(3): 419. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12724613&dopt=Abstract
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Survival in Duchenne muscular dystrophy: improvements in life expectancy since 1967 and the impact of home nocturnal ventilation. Author(s): Eagle M, Baudouin SV, Chandler C, Giddings DR, Bullock R, Bushby K. Source: Neuromuscular Disorders : Nmd. 2002 December; 12(10): 926-9. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12467747&dopt=Abstract
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Swallowing in myotonic muscular dystrophy: a videofluoroscopic study. Author(s): Leonard RJ, Kendall KA, Johnson R, McKenzie S. Source: Archives of Physical Medicine and Rehabilitation. 2001 July; 82(7): 979-85. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11441389&dopt=Abstract
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Targeted exon skipping as a potential gene correction therapy for Duchenne muscular dystrophy. Author(s): Aartsma-Rus A, Bremmer-Bout M, Janson AA, den Dunnen JT, van Ommen GJ, van Deutekom JC. Source: Neuromuscular Disorders : Nmd. 2002 October; 12 Suppl 1: S71-7. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12206800&dopt=Abstract
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Thallium-201 single photon emission computed tomography (SPECT) in patients with duchenne's progressive muscular dystrophy: a histopathologic correlation study. Author(s): Nishimura T, Yanagisawa A, Sakata H, Sakata K, Shimoyama K, Ishihara T, Yoshino H, Ishikawa K. Source: Japanese Circulation Journal. 2001 February; 65(2): 99-105. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11216833&dopt=Abstract
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The ABC's of limb-girdle muscular dystrophy: alpha-sarcoglycanopathy, Bethlem myopathy, calpainopathy and more. Author(s): Gordon ES, Hoffman EP. Source: Current Opinion in Neurology. 2001 October; 14(5): 567-73. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11562567&dopt=Abstract
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The abnormal expression of utrophin in Duchenne and Becker muscular dystrophy is age related. Author(s): Taylor J, Muntoni F, Dubowitz V, Sewry CA. Source: Neuropathology and Applied Neurobiology. 1997 October; 23(5): 399-405. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=9364465&dopt=Abstract
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The anesthetic management of a patient with Emery-Dreifuss muscular dystrophy for orthopedic surgery. Author(s): Aldwinckle RJ, Carr AS. Source: Canadian Journal of Anaesthesia = Journal Canadien D'anesthesie. 2002 May; 49(5): 467-70. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11983660&dopt=Abstract
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The A-type lamins: nuclear structural proteins as a focus for muscular dystrophy and cardiovascular diseases. Author(s): Mounkes LC, Burke B, Stewart CL. Source: Trends in Cardiovascular Medicine. 2001 October; 11(7): 280-5. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11709282&dopt=Abstract
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The cerebellar and thalamic degeneration in Fukuyama-type congenital muscular dystrophy. Author(s): Kumada S, Tsuchiya K, Takahashi M, Takesue M, Shiotsu H, Nomura Y, Segawa M, Ikeda K, Hayashi M. Source: Acta Neuropathologica. 2000 February; 99(2): 209-13. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10672329&dopt=Abstract
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The clinical and molecular genetic approach to Duchenne and Becker muscular dystrophy: an updated protocol. Author(s): van Essen AJ, Kneppers AL, van der Hout AH, Scheffer H, Ginjaar IB, ten Kate LP, van Ommen GJ, Buys CH, Bakker E. Source: Journal of Medical Genetics. 1997 October; 34(10): 805-12. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=9350811&dopt=Abstract
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The Duchenne de Boulogne-Meryon controversy and pseudohypertrophic muscular dystrophy. Author(s): Bach JR. Source: Journal of the History of Medicine and Allied Sciences. 2000 April; 55(2): 158-78. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10820967&dopt=Abstract
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The effect of motor learning in facioscapulohumeral muscular dystrophy patients. Author(s): Bakhtiary AH, Phoenix J, Edwards RH, Frostick SP. Source: European Journal of Applied Physiology. 2000 December; 83(6): 551-8. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11192064&dopt=Abstract
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The effects of knee-ankle-foot orthoses in the treatment of Duchenne muscular dystrophy: review of the literature. Author(s): Bakker JP, de Groot IJ, Beckerman H, de Jong BA, Lankhorst GJ. Source: Clinical Rehabilitation. 2000 August; 14(4): 343-59. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10945419&dopt=Abstract
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The Emery-Dreifuss Muscular Dystrophy Mutation Database. Author(s): Yates JR, Wehnert M. Source: Neuromuscular Disorders : Nmd. 1999 May; 9(3): 199. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10382916&dopt=Abstract
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The Emery-Dreifuss muscular dystrophy phenotype arises from aberrant targeting and binding of emerin at the inner nuclear membrane. Author(s): Fairley EA, Kendrick-Jones J, Ellis JA. Source: Journal of Cell Science. 1999 August; 112 ( Pt 15): 2571-82. Erratum In: J Cell Sci 1999 December; 112(Pt 24): Following 4800. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10393813&dopt=Abstract
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The expression of ion channel mRNAs in skeletal muscles from patients with myotonic muscular dystrophy. Author(s): Kimura T, Takahashi MP, Okuda Y, Kaido M, Fujimura H, Yanagihara T, Sakoda S. Source: Neuroscience Letters. 2000 December 8; 295(3): 93-6. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11090982&dopt=Abstract
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The Fukuyama congenital muscular dystrophy story. Author(s): Toda T, Kobayashi K, Kondo-Iida E, Sasaki J, Nakamura Y. Source: Neuromuscular Disorders : Nmd. 2000 March; 10(3): 153-9. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10734260&dopt=Abstract
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The future of Duchenne muscular dystrophy gene therapy: shrinking the dystrophin gene. Author(s): Roberts M, Dickson G. Source: Curr Opin Mol Ther. 2002 August; 4(4): 343-8. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12222872&dopt=Abstract
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The gene for a novel glycosyltransferase is mutated in congenital muscular dystrophy MDC1C and limb girdle muscular dystrophy 2I. Author(s): Brockington M, Blake DJ, Brown SC, Muntoni F. Source: Neuromuscular Disorders : Nmd. 2002 March; 12(3): 233-4. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11801394&dopt=Abstract
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The illness experience of adult persons with muscular dystrophy. Author(s): Natterlund B, Sjoden PO, Ahlstrom G. Source: Disability and Rehabilitation. 2001 November 20; 23(17): 788-98. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11762881&dopt=Abstract
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The IVth workshop on Duchenne muscular dystrophy gene therapy. Author(s): Schwartz K, Leterrier F. Source: The Journal of Gene Medicine. 1999 November-December; 1(6): 444-8. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10753071&dopt=Abstract
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The neurobiology of duchenne muscular dystrophy: learning lessons from muscle? Author(s): Blake DJ, Kroger S. Source: Trends in Neurosciences. 2000 March; 23(3): 92-9. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10675908&dopt=Abstract
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The new frontier in muscular dystrophy research: booster genes. Author(s): Engvall E, Wewer UM. Source: The Faseb Journal : Official Publication of the Federation of American Societies for Experimental Biology. 2003 September; 17(12): 1579-84. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12958164&dopt=Abstract
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The nuclear envelope in muscular dystrophy and cardiovascular diseases. Author(s): Burke B, Mounkes LC, Stewart CL. Source: Traffic (Copenhagen, Denmark). 2001 October; 2(10): 675-83. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11576443&dopt=Abstract
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The nuclear envelope, muscular dystrophy and gene expression. Author(s): Wilson KL. Source: Trends in Cell Biology. 2000 April; 10(4): 125-9. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10740265&dopt=Abstract
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The Peter Emil Becker Award lecture 1998. The saga of congenital muscular dystrophy. Author(s): Tome FM. Source: Neuropediatrics. 1999 April; 30(2): 55-65. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10401686&dopt=Abstract
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The product of an oculopharyngeal muscular dystrophy gene, poly(A)-binding protein 2, interacts with SKIP and stimulates muscle-specific gene expression. Author(s): Kim YJ, Noguchi S, Hayashi YK, Tsukahara T, Shimizu T, Arahata K. Source: Human Molecular Genetics. 2001 May 15; 10(11): 1129-39. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11371506&dopt=Abstract
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The role of basal and myogenic factors in the transcriptional activation of utrophin promoter A: implications for therapeutic up-regulation in Duchenne muscular dystrophy. Author(s): Perkins KJ, Burton EA, Davies KE. Source: Nucleic Acids Research. 2001 December 1; 29(23): 4843-50. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11726694&dopt=Abstract
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The role of the GlcNAc(beta)1,2Man(alpha)- moiety in mammalian development. Null mutations of the genes encoding UDP-N-acetylglucosamine:alpha-3-Dmannoside beta-1,2-N-acetylglucosaminyltransferase I and UDP-Nacetylglucosamine:alpha-D-mannoside beta-1,2-N-acetylglucosaminyltransferase I.2 cause embryonic lethality and congenital muscular dystrophy in mice and men, respectively. Author(s): Schachter H. Source: Biochimica Et Biophysica Acta. 2002 December 19; 1573(3): 292-300. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12417411&dopt=Abstract
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The role of the nuclear envelope in Emery-Dreifuss muscular dystrophy. Author(s): Morris GE. Source: Trends in Molecular Medicine. 2001 December; 7(12): 572-7. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11733221&dopt=Abstract
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The role of utrophin in the potential therapy of Duchenne muscular dystrophy. Author(s): Perkins KJ, Davies KE. Source: Neuromuscular Disorders : Nmd. 2002 October; 12 Suppl 1: S78-89. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12206801&dopt=Abstract
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The serum nitric oxide levels in patients with Duchenne muscular dystrophy. Author(s): Gucuyener K, Ergenekon E, Erbas D, Pinarli G, Serdaroglu A. Source: Brain & Development. 2000 May; 22(3): 181-3. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10814901&dopt=Abstract
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The shoulder in patients with muscular dystrophy. Author(s): Copeland SA, Levy O, Warner GC, Dodenhoff RM. Source: Clinical Orthopaedics and Related Research. 1999 November; (368): 80-91. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10613155&dopt=Abstract
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The strength and functional performance in patients with facioscapulohumeral muscular dystrophy. Author(s): Lue YJ, Chen SS. Source: Kaohsiung J Med Sci. 2000 May; 16(5): 248-54. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10969520&dopt=Abstract
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The structure of the N-terminal actin-binding domain of human dystrophin and how mutations in this domain may cause Duchenne or Becker muscular dystrophy. Author(s): Norwood FL, Sutherland-Smith AJ, Keep NH, Kendrick-Jones J. Source: Structure with Folding & Design. 2000 May 15; 8(5): 481-91. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10801490&dopt=Abstract
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The treatment of scoliosis in muscular dystrophy using modified Luque and Harrington-Luque instrumentation. Author(s): Bentley G, Haddad F, Bull TM, Seingry D. Source: The Journal of Bone and Joint Surgery. British Volume. 2001 January; 83(1): 22-8. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11245532&dopt=Abstract
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The use of multiple anti-dystrophin antibodies in Duchenne and Becker muscular dystrophy. Author(s): Kuriakides T. Source: Journal of Neurology, Neurosurgery, and Psychiatry. 1993 October; 56(10): 11378. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=8410021&dopt=Abstract
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The Xq22 inversion breakpoint interrupted a novel Ras-like GTPase gene in a patient with Duchenne muscular dystrophy and profound mental retardation. Author(s): Saito-Ohara F, Fukuda Y, Ito M, Agarwala KL, Hayashi M, Matsuo M, Imoto I, Yamakawa K, Nakamura Y, Inazawa J. Source: American Journal of Human Genetics. 2002 September; 71(3): 637-45. Epub 2002 July 23. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12145744&dopt=Abstract
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Therapeutic possibilities in muscular dystrophy: the hope versus the hype. Author(s): Dubowitz V. Source: Neuromuscular Disorders : Nmd. 2002 February; 12(2): 113-6. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11738351&dopt=Abstract
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Three wishes and psychological functioning in boys with duchenne muscular dystrophy. Author(s): Nereo NE, Hinton VJ. Source: Journal of Developmental and Behavioral Pediatrics : Jdbp. 2003 April; 24(2): 96103. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12692454&dopt=Abstract
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Thrombotic risk of muscular dystrophy: protein C deficiency, factor V Leiden, and myotonic dystrophy. Author(s): Cobos E, Phy M, Keung YK. Source: Clinical and Applied Thrombosis/Hemostasis : Official Journal of the International Academy of Clinical and Applied Thrombosis/Hemostasis. 1999 July; 5(3): 185-6. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10726006&dopt=Abstract
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Tibial muscular dystrophy is a titinopathy caused by mutations in TTN, the gene encoding the giant skeletal-muscle protein titin. Author(s): Hackman P, Vihola A, Haravuori H, Marchand S, Sarparanta J, De Seze J, Labeit S, Witt C, Peltonen L, Richard I, Udd B. Source: American Journal of Human Genetics. 2002 September; 71(3): 492-500. Epub 2002 July 26. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12145747&dopt=Abstract
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Time dependent changes of variables associated with malocclusion in patients with Duchenne muscular dystrophy. Author(s): Matsumoto S, Morinushi T, Ogura T. Source: J Clin Pediatr Dent. 2002 Fall; 27(1): 53-61. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12413173&dopt=Abstract
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Tongue atrophy in facioscapulohumeral muscular dystrophy. Author(s): Yamanaka G, Goto K, Matsumura T, Funakoshi M, Komori T, Hayashi YK, Arahata K. Source: Neurology. 2001 August 28; 57(4): 733-5. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11524495&dopt=Abstract
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Total intravenous anaesthesia without muscle relaxants in a child with diagnosed Duchenne muscular dystrophy. Author(s): Capozzoli G, Auricchio F, Accinelli G. Source: Minerva Anestesiol. 2000 November; 66(11): 839-40. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11213553&dopt=Abstract
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Towards the control of a powered orthosis for people with muscular dystrophy. Author(s): Rahman T, Ramanathan R, Stroud S, Sample W, Seliktar R, Harwin W, Alexander M, Scavina M. Source: Proceedings of the Institution of Mechanical Engineers. Part H, Journal of Engineering in Medicine. 2001; 215(3): 267-74. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11436269&dopt=Abstract
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Tracheobronchomalacia and tracheal hemorrhage in patients with Duchenne muscular dystrophy receiving long-term ventilation with uncuffed tracheostomies. Author(s): Baydur A, Kanel G. Source: Chest. 2003 April; 123(4): 1307-11. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12684330&dopt=Abstract
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Transaminitis in Duchenne's muscular dystrophy. Author(s): Tay SK, Ong HT, Low PS. Source: Ann Acad Med Singapore. 2000 November; 29(6): 719-22. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11269976&dopt=Abstract
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Transcriptional activation of the non-muscle, full-length dystrophin isoforms in Duchenne muscular dystrophy skeletal muscle. Author(s): Sironi M, Bardoni A, Felisari G, Cagliani R, Robotti M, Comi GP, Moggio M, Bresolin N. Source: Journal of the Neurological Sciences. 2001 May 1; 186(1-2): 51-7. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11412872&dopt=Abstract
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Transportation of a client with muscular dystrophy on commercial air: a unique setting for a rehabilitation nurse. Author(s): Klemme KL. Source: Rehabilitation Nursing : the Official Journal of the Association of Rehabilitation Nurses. 2003 March-April; 28(2): 40-1. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12673974&dopt=Abstract
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Troponin T and troponin I in carriers of Duchenne and Becker muscular dystrophy with cardiac involvement. Author(s): Hoogerwaard EM, Schouten Y, van der Kooi AJ, Gorgels JP, de Visser M, Sanders GT. Source: Clinical Chemistry. 2001 May; 47(5): 962-3. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11325912&dopt=Abstract
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Ullrich scleroatonic muscular dystrophy is caused by recessive mutations in collagen type VI. Author(s): Camacho Vanegas O, Bertini E, Zhang RZ, Petrini S, Minosse C, Sabatelli P, Giusti B, Chu ML, Pepe G. Source: Proceedings of the National Academy of Sciences of the United States of America. 2001 June 19; 98(13): 7516-21. Epub 2001 May 29. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11381124&dopt=Abstract
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Ultrasound tissue characterization detects preclinical myocardial structural changes in children affected by Duchenne muscular dystrophy. Author(s): Giglio V, Pasceri V, Messano L, Mangiola F, Pasquini L, Dello Russo A, Damiani A, Mirabella M, Galluzzi G, Tonali P, Ricci E. Source: Journal of the American College of Cardiology. 2003 July 16; 42(2): 309-16. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12875769&dopt=Abstract
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Ultrastructural abnormality of sarcolemmal nuclei in Emery-Dreifuss muscular dystrophy (EDMD). Author(s): Fidzianska A, Toniolo D, Hausmanowa-Petrusewicz I. Source: Journal of the Neurological Sciences. 1998 July 15; 159(1): 88-93. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=9700709&dopt=Abstract
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Unequal crossing-over in unique PABP2 mutations in Japanese patients: a possible cause of oculopharyngeal muscular dystrophy. Author(s): Nakamoto M, Nakano S, Kawashima S, Ihara M, Nishimura Y, Shinde A, Kakizuka A. Source: Archives of Neurology. 2002 March; 59(3): 474-7. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11890856&dopt=Abstract
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Uniparental disomy of the entire X chromosome in a female with Duchenne muscular dystrophy. Author(s): Quan F, Janas J, Toth-Fejel S, Johnson DB, Wolford JK, Popovich BW. Source: American Journal of Human Genetics. 1997 January; 60(1): 160-5. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=8981959&dopt=Abstract
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Unique PABP2 mutations in “Cajuns” suggest multiple founders of oculopharyngeal muscular dystrophy in populations with French ancestry. Author(s): Scacheri PC, Garcia C, Hebert R, Hoffman EP. Source: American Journal of Medical Genetics. 1999 October 29; 86(5): 477-81. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10508991&dopt=Abstract
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Unusual expression and very mild course of Xp21 muscular dystrophy (Becker type) in a 60-year-old man with 26 percent deletion of the dystrophin gene. Author(s): Palmucci L, Doriguzzi C, Mongini T, Restagno G, Chiado-Piat L, Maniscalco M. Source: Neurology. 1994 March; 44(3 Pt 1): 541-3. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=8145928&dopt=Abstract
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Unusual expression of emerin in a patient with X-linked Emery-Dreifuss muscular dystrophy. Author(s): Di Blasi C, Morandi L, Raffaele di Barletta M, Bione S, Bernasconi P, Cerletti M, Bono R, Blasevich F, Toniolo D, Mora M. Source: Neuromuscular Disorders : Nmd. 2000 December; 10(8): 567-71. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11053683&dopt=Abstract
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Unusual laminin alpha2 processing in myoblasts from a patient with a novel variant of congenital muscular dystrophy. Author(s): Lattanzi G, Muntoni F, Sabatelli P, Squarzoni S, Maraldi NM, Cenni V, Villanova M, Columbaro M, Merlini L, Marmiroli S. Source: Biochemical and Biophysical Research Communications. 2000 November 2; 277(3): 639-42. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11062006&dopt=Abstract
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Unusual triplet expansion associated with neurogenic changes in a family with oculopharyngeal muscular dystrophy. Author(s): Schober R, Kress W, Grahmann F, Kellermann S, Baum P, Gunzel S, Wagner A. Source: Neuropathology : Official Journal of the Japanese Society of Neuropathology. 2001 March; 21(1): 45-52. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11304042&dopt=Abstract
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Upper esophageal sphincter myotomy in oculopharyngeal muscular dystrophy: longterm clinical results. Author(s): Fradet G, Pouliot D, Robichaud R, St-Pierre S, Bouchard JP. Source: Neuromuscular Disorders : Nmd. 1997 October; 7 Suppl 1: S90-5. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=9392024&dopt=Abstract
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Up-regulation of the brain and Purkinje-cell forms of dystrophin transcripts, in Becker muscular dystrophy. Author(s): Nakamura A, Ikeda S, Yazaki M, Yoshida K, Kobayashi O, Yanagisawa N, Takeda S. Source: American Journal of Human Genetics. 1997 June; 60(6): 1555-8. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=9199582&dopt=Abstract
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Upregulation of utrophin in the myocardium of a carrier of Duchenne muscular dystrophy. Author(s): Behr TM, Fischer P, Mudra H, Theisen K, Spes C, Uberfuhr P, Muller-Felber W, Pongratz DE, Angermann C. Source: European Heart Journal. 1997 April; 18(4): 699-700. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=9129907&dopt=Abstract
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Urinary dysfunction in Duchenne muscular dystrophy. Author(s): Caress JB, Kothari MJ, Bauer SB, Shefner JM. Source: Muscle & Nerve. 1996 July; 19(7): 819-22. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=8965833&dopt=Abstract
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Urinary excretion of acid-soluble peptides in children with Duchenne muscular dystrophy. Author(s): Hirano K, Sakamoto Y. Source: Acta Paediatr Jpn. 1994 December; 36(6): 627-31. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=7871971&dopt=Abstract
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Use of a CEPH meiotic breakpoint panel to refine the locus of limb-girdle muscular dystrophy type 1A (LGMD1A) to a 2-Mb interval on 5q31. Author(s): Bartoloni L, Horrigan SK, Viles KD, Gilchrist JM, Stajich JM, Vance JM, Yamaoka LH, Pericak-Vance MA, Westbrook CA, Speer MC. Source: Genomics. 1998 December 1; 54(2): 250-5. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=9828127&dopt=Abstract
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Usefulness of dinucleotide polymorphism markers in genetic analysis of Duchenne's muscular dystrophy cases in Singapore. Author(s): Lai PS, Chiu LL, Low PS, Lee WL, Tay JS. Source: Southeast Asian J Trop Med Public Health. 1995; 26 Suppl 1: 175-8. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=8629101&dopt=Abstract
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Usefulness of test: manual muscle testing, goniometry, and daily activities for differential diagnosis of Duchenne muscular dystrophy, Becker's mild muscular dystrophy and Becker's severe muscular dystrophy. Author(s): Alvarez M, Rodriguez I, Zuniga-Charles MA. Source: International Journal of Rehabilitation Research. Internationale Zeitschrift Fur Rehabilitationsforschung. Revue Internationale De Recherches De Readaptation. 1998 March; 21(1): 79-85. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=9924669&dopt=Abstract
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Using neural networks as an aid in the determination of disease status: comparison of clinical diagnosis to neural-network predictions in a pedigree with autosomal dominant limb-girdle muscular dystrophy. Author(s): Falk CT, Gilchrist JM, Pericak-Vance MA, Speer MC. Source: American Journal of Human Genetics. 1998 April; 62(4): 941-9. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=9529338&dopt=Abstract
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Using the full power of linkage analysis in 11 French Canadian families to fine map the oculopharyngeal muscular dystrophy gene. Author(s): Brais B, Bouchard JP, Gosselin F, Xie YG, Fardeau M, Tome FM, Rouleau GA. Source: Neuromuscular Disorders : Nmd. 1997 October; 7 Suppl 1: S70-4. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=9392020&dopt=Abstract
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Vaginal delivery in a woman with limb-girdle muscular dystrophy. A case report. Author(s): Ayoubi JM, Meddoun M, Jouk PS, Favier M, Pons JC. Source: J Reprod Med. 2000 June; 45(6): 498-500. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10900585&dopt=Abstract
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Valley sign in duchenne muscular dystrophy: importance in patients with inconspicuous calves. Author(s): Pradhan S. Source: Neurology India. 2002 June; 50(2): 184-6. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12134184&dopt=Abstract
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Value of myofibrillar protein catabolic rate in Duchenne muscular dystrophy. A study after lower limb surgery. Author(s): Forst J, Kruger P, Forst R. Source: Archives of Orthopaedic and Trauma Surgery. 2000; 120(1-2): 38-41. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10653102&dopt=Abstract
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Variable clinical phenotype in merosin-deficient congenital muscular dystrophy associated with differential immunolabelling of two fragments of the laminin alpha 2 chain. Author(s): Sewry CA, Naom I, D'Alessandro M, Sorokin L, Bruno S, Wilson LA, Dubowitz V, Muntoni F. Source: Neuromuscular Disorders : Nmd. 1997 May; 7(3): 169-75. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=9185180&dopt=Abstract
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Variable histomorphology of muscle in congenital muscular dystrophy. Author(s): Das S, Gayathri N, Gourie-Devi M, Anisya-Vasanth AV, Ramamohan Y. Source: Journal of the Neurological Sciences. 1997 August; 149(2): 157-63. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=9171324&dopt=Abstract
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Vascular tortuosity and Coats'-like retinal changes in facioscapulohumeral muscular dystrophy. Author(s): Tekin NF, Saatci AO, Kavukcu S. Source: Ophthalmic Surgery and Lasers. 2000 January-February; 31(1): 82-3. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10976570&dopt=Abstract
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Ventricular tachycardia in Duchenne's muscular dystrophy. Author(s): Munoz J, Sanjuan R, Morell JS, Ibanez M. Source: International Journal of Cardiology. 1996 June; 54(3): 259-62. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=8818749&dopt=Abstract
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Vertebral compression in Duchenne muscular dystrophy following deflazacort. Author(s): Talim B, Malaguti C, Gnudi S, Politano L, Merlini L. Source: Neuromuscular Disorders : Nmd. 2002 March; 12(3): 294-5. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11801403&dopt=Abstract
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Vertebral fractures in boys with Duchenne muscular dystrophy. Author(s): Bothwell JE, Gordon KE, Dooley JM, MacSween J, Cummings EA, Salisbury S. Source: Clinical Pediatrics. 2003 May; 42(4): 353-6. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12800730&dopt=Abstract
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Visual function in children with merosin-deficient and merosin-positive congenital muscular dystrophy. Author(s): Mercuri E, Anker S, Philpot J, Sewry C, Dubowitz V, Muntoni F. Source: Pediatric Neurology. 1998 May; 18(5): 399-401. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=9650678&dopt=Abstract
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Walker-Warburg syndrome is genetically distinct from Fukuyama type congenital muscular dystrophy. Author(s): Chadani Y, Kondoh T, Kamimura N, Matsumoto T, Matsuzaka T, Kobayashi O, Kondo-Iida E, Kobayashi K, Nonaka I, Toda T. Source: Journal of the Neurological Sciences. 2000 August 15; 177(2): 150-3. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10980312&dopt=Abstract
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What is muscular dystrophy? Forty years of progressive ignorance. Author(s): Dubowitz V. Source: Journal of the Royal College of Physicians of London. 2000 September-October; 34(5): 464-8. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11077661&dopt=Abstract
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What's in a name? Muscular dystrophy revisited. Author(s): Dubowitz V. Source: European Journal of Paediatric Neurology : Ejpn : Official Journal of the European Paediatric Neurology Society. 1998; 2(6): 279-84. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10727193&dopt=Abstract
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What's new in neuromuscular disorders? Nuclear envelope and Emery-Dreifuss muscular dystrophy. Author(s): Mercuri E, Muntoni F. Source: European Journal of Paediatric Neurology : Ejpn : Official Journal of the European Paediatric Neurology Society. 2001; 5(1): 3-5. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11277362&dopt=Abstract
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White matter abnormalities in congenital muscular dystrophy. Author(s): Leyten QH, Gabreels FJ, Renier WO, van Engelen BG, ter Laak HJ, Sengers RC, Thijssen HO. Source: Journal of the Neurological Sciences. 1995 April; 129(2): 162-9. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=7608731&dopt=Abstract
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Why did the heated discussion arise between Erb and Landouzy-Dejerine concerning the priority in describing the facio-scapulo-humeral muscular dystrophy and what is the main reason for this famous discussion? Author(s): Kazakov V. Source: Neuromuscular Disorders : Nmd. 2001 May; 11(4): 421. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11369197&dopt=Abstract
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Why is the reproductive performance lower in Becker (BMD) as compared to limb girdle (LGMD) muscular dystrophy male patients? Author(s): Eggers S, Lauriano V, Melo M, Takata RI, Akiyama J, Passos-Bueno MR, Gentil V, Frota-Pessoa O, Zatz M. Source: American Journal of Medical Genetics. 1995 February 27; 60(1): 27-32. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=7485231&dopt=Abstract
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X-chromosomal (p21) muscular dystrophy and left ventricular diastolic and systolic function. Author(s): Brockmeier K, Schmitz L, von Moers A, Koch H, Vogel M, Bein G. Source: Pediatric Cardiology. 1998 March-April; 19(2): 139-44. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=9565505&dopt=Abstract
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X-linked Emery-Dreifuss muscular dystrophy can be diagnosed from skin biopsy or blood sample. Author(s): Mora M, Cartegni L, Di Blasi C, Barresi R, Bione S, Raffaele di Barletta M, Morandi L, Merlini L, Nigro V, Politano L, Donati MA, Cornelio F, Cobianchi F, Toniolo D. Source: Annals of Neurology. 1997 August; 42(2): 249-53. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=9266737&dopt=Abstract
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Xp21 muscular dystrophy due to X chromosome inversion. Author(s): Baxter PS, Maltby EL, Quarrell O. Source: Neurology. 1997 July; 49(1): 260. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=9222202&dopt=Abstract
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YAC and cosmid contigs encompassing the Fukuyama-type congenital muscular dystrophy (FCMD) candidate region on 9q31. Author(s): Miyake M, Nakahori Y, Matsushita I, Kobayashi K, Mizuno K, Hirai M, Kanazawa I, Nakagome Y, Tokunaga K, Toda T. Source: Genomics. 1997 March 1; 40(2): 284-93. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=9119396&dopt=Abstract
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YAC contigs for 4q35 in the region of the facioscapulohumeral muscular dystrophy (FSHD) gene. Author(s): Weiffenbach B, Dubois J, Manning S, Ma NS, Schutte BC, Winokur ST, Altherr MR, Jacobsen SJ, Stanton VP Jr, Yokoyama K, et al. Source: Genomics. 1994 February; 19(3): 532-41. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=8188296&dopt=Abstract
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You need more than nocturnal NIPPV to manage Duchenne's muscular dystrophy. Author(s): Bach JR. Source: Chest. 1995 February; 107(2): 592. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=7842813&dopt=Abstract
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CHAPTER 2. NUTRITION AND MUSCULAR DYSTROPHY Overview In this chapter, we will show you how to find studies dedicated specifically to nutrition and muscular dystrophy.
Finding Nutrition Studies on Muscular Dystrophy 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 “muscular dystrophy” (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 “muscular dystrophy” (or a synonym): •
A tetrodotoxin- and Mn2(+)-insensitive Na+ current in Duchenne muscular dystrophy. Author(s): Department of Physiology and Biophysics, Faculty of Medicine, University of Sherbrooke, Quebec, Canada. Source: Bkaily, G Jasmin, G Tautu, C Prochek, L Yamamoto, T Sculptoreanu, A Peyrow, M Jacques, D Muscle-Nerve. 1990 October; 13(10): 939-48 0148-639X
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Abnormal calcium homeostasis in Duchenne muscular dystrophy myotubes contracting in vitro. Author(s): Laboratoire de Physiologie Generale, URA CNRS 1869, Universite de Poitiers, France. Source: Imbert, N Cognard, C Duport, G Guillou, C Raymond, G Cell-Calcium. 1995 September; 18(3): 177-86 0143-4160
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Becker and limb-girdle muscular dystrophy associated with pituitary dwarfism. Author(s): Department of Neurology, University of Florence, Italy. Source: Marconi, G Taiuti, R Sbrilli, C Pizzi, A J-Neurol. 1987 August; 234(6): 430-2 03405354
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Becker muscular dystrophy-related cardiomyopathy: a favorable response to medical therapy. Author(s): Division of Cardiology, University of Utah School of Medicine, Salt Lake City, Utah 84132, USA. Source: Doing, Anthony H Renlund, Dale G Smith, Ruth Ann J-Heart-Lung-Transplant. 2002 April; 21(4): 496-8 1053-2498
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Biochemical changes in progressive muscular dystrophy. XV. Distribution of radioactive glutamate and proximate composition of various components of skeletal muscle and liver in vitamin E-deficient dystrophic rabbits and 129/ReJ (dy/dy) mice. Author(s): Departement de Nutrition, Universite de Montreal, Quebec, Canada. Source: Srivastava, U S Goswami, T Exp-Biol. 1988; 47(3): 185-93 0176-8638
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Biochemical effect of naturally and experimental induced nutritional muscular dystrophy on copper and iron levels in plasmas of suckling Egyptian buffalo calves. Source: El Neweehy, T.K. Amer, H.A. Abd el Salam, S.A. Arch-Exp-Veterinarmed. Leipzig, E. Ger. : S. Hirzel. 1985. volume 39 (6) page 859-863. 0003-9055
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Calcium homeostasis and ultrastructural studies in a patient with limb girdle muscular dystrophy type 2C. Author(s): Muscular Dystrophy Research Laboratories, Newcastle General Hospital, Newcastle upon Tyne, UK. Source: Hassoni, A A Cullen, M J Neuropathol-Appl-Neurobiol. 1999 June; 25(3): 244-53 0305-1846
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Carnitine deficiency, mitochondrial dysfunction and the heart. Identical defect of oxidative phosphorylation in muscle mitochondria in cardiomyopathy due to carnitine loss and in Duchenne muscular dystrophy. Author(s): Department of Biochemistry I, Erasmus University Rotterdam, The Netherlands. Source: Scholte, H R Rodrigues Pereira, R Busch, H F Jennekens, F G Luyt Houwen, I E Vaandrager Verduin, M H Wien-Klin-Wochenschr. 1989 January 6; 101(1): 12-7 00435325
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Changes in cytosolic resting ionized calcium level and in calcium transients during in vitro development of normal and Duchenne muscular dystrophy cultured skeletal muscle measured by laser cytofluorimetry using indo-1. Author(s): Laboratoire de Physiologie Generale, URA CNRS n 290, Universite de Poitiers, France. Source: Rivet Bastide, M Imbert, N Cognard, C Duport, G Rideau, Y Raymond, G CellCalcium. 1993 July; 14(7): 563-71 0143-4160
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Clinical investigation in Duchenne muscular dystrophy: penicillamine and vitamin E. Author(s): Department of Neurology, Vanderbilt University School of Medicine, Nashville, TN 37212. Source: Fenichel, G M Brooke, M H Griggs, R C Mendell, J R Miller, J P Moxley, R T 3rd Park, J H Provine, M A Florence, J Kaiser, K K et al. Muscle-Nerve. 1988 November; 11(11): 1164-8 0148-639X
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Coenzyme Q10, exercise lactate and CTG trinucleotide expansion in myotonic dystrophy. Author(s): Department of Neuroscience, Neurological Clinics, University of Pisa, Pisa, Italy.
[email protected] Source: Siciliano, G Mancuso, M Tedeschi, D Manca, M L Renna, M R Lombardi, V Rocchi, A Martelli, F Murri, L Brain-Res-Bull. 2001 Oct-November 1; 56(3-4): 405-10 0361-9230
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Cortical and brainstem neurons containing calcium-binding proteins in a murine model of Duchenne's muscular dystrophy: selective changes in the sensorimotor cortex. Author(s): Department of Neurological and Psychiatric Sciences, University of Florence, Florence, Italy, I-50134. Source: Carretta, D Santarelli, M Vanni, D Ciabatti, S Sbriccoli, A Pinto, F Minciacchi, D J-Comp-Neurol. 2003 January 27; 456(1): 48-59 0021-9967
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Corticosteroids in Duchenne muscular dystrophy: a reappraisal. Author(s): Division of Child Neurology, Children's Hospital Medical Center, Cincinnati, OH 45229-3039, USA.
[email protected] Source: Wong, B L Christopher, C J-Child-Neurol. 2002 March; 17(3): 183-90 0883-0738
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Depressed myocardial fatty acid metabolism in patients with muscular dystrophy. Author(s): Department of Cardiology, Tokyo Metropolitan Fuchu Hospital, Musashidai 2-5-2, Fuchu, Tokyo, Japan.
[email protected] Source: Momose, M Iguchi, N Imamura, K Usui, H Ueda, T Miyamoto, K Inaba, S Neuromuscul-Disord. 2001 July; 11(5): 464-9 0960-8966
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Duchenne muscular dystrophy and concomitant metastatic alveolar rhabdomyosarcoma. Author(s): Division of Pediatric Hematology/Oncology, All Children's Hospital, University of South Florida College of Medicine, St. Petersburg, USA. Source: Rossbach, H C Lacson, A Grana, N H Barbosa, J L J-Pediatr-Hematol-Oncol. 1999 Nov-December; 21(6): 528-30 1077-4114
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Effect of intraperitoneal injection of glucose on glucose oxidation and energy expenditure in the mdx mouse model of duchenne muscular dystrophy. Author(s): Lab. de Neurobiologie des Regulations, C.N.R.S. URA 1860 College de France, 11 Pl. M. Berthelot, F-75231 Paris Cedex 05, France. Source: Mokhtarian, A Even, P C Pflugers-Arch. 1996 July; 432(3): 379-85 0031-6768
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Electrocardiographic findings in mdx mice: a cardiac phenotype of Duchenne muscular dystrophy. Author(s): Cardiovascular Division, Beth Israel Deaconess Medical Center, Harvard Medical School, 330 Brookline Avenue, Boston, Massachusetts 02215, USA. Source: Chu, V Otero, J M Lopez, O Sullivan, M F Morgan, J P Amende, I Hampton, T G Muscle-Nerve. 2002 October; 26(4): 513-9 0148-639X
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Emerin, deficiency of which causes Emery-Dreifuss muscular dystrophy, is localized at the inner nuclear membrane. Author(s): Department of Anatomy II, National Defense Medical College, Saitama, Japan. Source: Yorifuji, H Tadano, Y Tsuchiya, Y Ogawa, M Goto, K Umetani, A Asaka, Y Arahata, K Neurogenetics. 1997 September; 1(2): 135-40 1364-6745
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Feeding problems in merosin deficient congenital muscular dystrophy. Author(s): Neuromuscular Unit, Department of Paediatrics and Neonatal Medicine, Imperial College School of Medicine, Hammersmith Hospital, Du Cane Road, London W12 ONN, UK. Source: Philpot, J Bagnall, A King, C Dubowitz, V Muntoni, F Arch-Dis-Child. 1999 June; 80(6): 542-7 0003-9888
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Hypothalamo-pituitary dopaminergic system in patients with myotonic dystrophy. Author(s): Department of Neurology, Tohoku University School of Medicine, Sendai. Source: Sakuma, H Takase, S Mizuno, Y Teramura, K Hanew, K Tohoku-J-Exp-Med. 1988 November; 156(3): 291-8 0040-8727
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Identifying and circumventing the defect in Duchenne muscular dystrophy: clinical and biochemical restoration after practical intervention. Author(s): Knightswood Hospital, Glasgow, U.K. Source: Thomson, W H Med-Hypotheses. 1987 October; 24(2): 187-90 0306-9877
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Immunohistochemical staining of dystrophin on formalin-fixed paraffin-embedded sections in Duchenne/Becker muscular dystrophy and manifesting carriers of Duchenne muscular dystrophy. Author(s): Department of Neurology, Institute of Clinical Medicine, University of Tsukuba, 305-8575, Tsukuba City, Japan. Source: Hoshino, S Ohkoshi, N Watanabe, M Shoji, S Neuromuscul-Disord. 2000 August; 10(6): 425-9 0960-8966
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Interactions of vitamin E and penicillamine in the treatment of hereditary avian muscular dystrophy. Author(s): Department of Medicine, Vanderbilt University School of Medicine, Nashville, TN 37232. Source: Serafin, W E Dement, S H Brandon, S Hill, E J Park, C R Park, J H Muscle-Nerve. 1987 October; 10(8): 685-97 0148-639X
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Intraruminal selenium pellet for control of nutritional muscular dystrophy in cattle. Source: Hidiroglou, M. Proulx, J. Jolette, J. J-Dairy-Sci. Champaign, Ill. : American Dairy Science Association. January 1985. volume 68 (1) page 57-66. 0022-0302
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Iron and copper levels in plasmas of suckling buffalo calves after prophylactic administration of selenium and vitamin E/selenium against nutritional muscular dystrophy. Source: Amer, H.A. El Neweehy, T.K. Abd el Salam, S.A. Arch-Exp-Veterinarmed. Leipzig, E. Ger. : S. Hirzel. 1985. volume 39 (6) page 852-858. 0003-9055
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Mice deficient in small leucine-rich proteoglycans: novel in vivo models for osteoporosis, osteoarthritis, Ehlers-Danlos syndrome, muscular dystrophy, and corneal diseases. Author(s): Craniofacial and Skeletal Diseases Branch, Building 30 Room 225, NIDCR, NIH, Bethesda, MD 20892, USA. Source: Ameye, L Young, M F Glycobiology. 2002 September; 12(9): 107R-16R 0959-6658
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Molecular pathophysiology and targeted therapeutics for muscular dystrophy. Author(s): Research Center for Genetic Medicine, Children's National Medical Center, Washington DC 20010, USA.
[email protected] Source: Hoffman, E P Dressman, D Trends-Pharmacol-Sci. 2001 September; 22(9): 465-70 0165-6147
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Nutritional muscular dystrophy in calves. Effect of administreing intraruminally Selenium pellets to pregnant cattle. Source: Hidiroglou, M. Proulx, J. Jolette, J. Trace elements in man and animals : TEMA 5 : proceedings of the fifth International Symposium on Trace Elements in Man and Animals / editors C.F. Mills, I. Bremner, & J.K. Chesters. Farnham Royal, Slough : Commonwealth Agricultural Bureaux, c1985. page 744-748. ISBN: 085198553X
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Nutritional muscular dystrophy in foals. Source: Moore, R.M. Kohn, C.W. Compend-Contin-Educ-Pract-Vet. Trenton, N.J. : Veterinary Learning Systems Company. March 1991. volume 13 (3) page 476-490. 01931903
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Oral creatine supplementation in Duchenne muscular dystrophy: a clinical and 31P magnetic resonance spectroscopy study. Author(s): Department of Radiology II and Magnetic Resonance, University of Innsbruck, Children's Hospital, LKH Salzburg, Austria. Source: Felber, S Skladal, D Wyss, M Kremser, C Koller, A Sperl, W Neurol-Res. 2000 March; 22(2): 145-50 0161-6412
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Pharmacologic and genetic therapy for childhood muscular dystrophies. Author(s): Department of Neurology, Research Center for Genetic Medicine, MDA Clinic, Children's National Medical Center, George Washington University, 111 Michigan Avenue NW, Washington, DC 20010, USA.
[email protected] Source: Escolar, D M Scacheri, C G Curr-Neurol-Neurosci-Repage 2001 March; 1(2): 16874 1528-4042
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Prednisolone in Duchenne muscular dystrophy. Author(s): Deptt. of Neuromedicine, SOMC, Sylhet. Source: Rahman, M M Hannan, M A Mondol, B A Bhoumick, N B Haque, A Bangladesh-Med-Res-Counc-Bull. 2001 April; 27(1): 38-42 0377-9238
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Properties of Ca2+-activated K+ channels in erythrocytes from patients with myotonic muscular dystrophy. Author(s): Dipartimento di Fisiologia e Biochimica G. Moruzzi, Universita di Pisa, Italy. Source: Pellegrino, M Pellegrini, M Bigini, P Scimemi, A Muscle-Nerve. 1998 November; 21(11): 1465-72 0148-639X
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Selenium and vitamin E treatment of Duchenne muscular dystrophy: no effect on muscle function. Author(s): Department of Neurophysiology, University Hospital, Linkoping, Sweden. Source: Backman, E Nylander, E Johansson, I Henriksson, K G Tagesson, C Acta-NeurolScand. 1988 November; 78(5): 429-35 0001-6314
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Some studies on nutritional muscular dystrophy in Qassim region in Saudi Arabia. Effect of administration of vitamin E-selenium preparation to pregnant ewes on serum muscle-specific enzymes in their lambs. Source: El Neweehy, T.K. Abdel Rahman, H.A. Al Qarawi, A.A. Small-rumin-res. Amsterdam; New York : Elsevier,. July 2001. volume 41 (1) page 87-89. 0921-4488
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The stabilizing effect of bestatin on the resting membrane potentials of X-linked muscular dystrophy mice. Author(s): Fourth Department of Medicine, Toho University School of Medicine, Tokyo, Japan. Source: Kishi, M Kurihara, T Hidaka, T Kinoshita, M Jpn-J-Psychiatry-Neurol. 1990 September; 44(3): 595-600 0912-2036
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Urinary excretion of selenium and other minerals in patients with Duchenne muscular dystrophy (M.D.) and Werdnig-Hoffman (W-H) spinal atrophy. Source: Ahlrot Westerlund, B. Carlmark, B. Nutr-Res. Elmsford, N.Y. : Pergamon Press. 1985. (suppl. 1) page 406-409. ill. 0271-5317
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Use of injectable vitamin E and selenium-vitamin E emulsion in ewes and suckling lambs to prevent nutritional muscular dystrophy. Source: Norton, S.A. McCarthy, F.D. J-Anim-Sci. Champaign, Ill. : American Society of Animal Science. February 1986. volume 62 (2) page 497-508. 0021-8812
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/
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Additional Web Resources A number of additional Web sites offer encyclopedic information covering food and nutrition. The following is a representative sample: •
AOL: http://search.aol.com/cat.adp?id=174&layer=&from=subcats
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Family Village: http://www.familyvillage.wisc.edu/med_nutrition.html
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Google: http://directory.google.com/Top/Health/Nutrition/
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Healthnotes: http://www.healthnotes.com/
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Open Directory Project: http://dmoz.org/Health/Nutrition/
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Yahoo.com: http://dir.yahoo.com/Health/Nutrition/
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WebMDHealth: http://my.webmd.com/nutrition
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WholeHealthMD.com: http://www.wholehealthmd.com/reflib/0,1529,00.html
The following is a specific Web list relating to muscular dystrophy; please note that any particular subject below may indicate either a therapeutic use, or a contraindication (potential danger), and does not reflect an official recommendation: •
Minerals Biotin Source: Integrative Medicine Communications; www.drkoop.com Carnitine Source: Prima Communications, Inc.www.personalhealthzone.com Creatine Source: WholeHealthMD.com, LLC. www.wholehealthmd.com Hyperlink: http://www.wholehealthmd.com/refshelf/substances_view/0,1525,10020,00.html Creatine Monohydrate Source: Healthnotes, Inc. www.healthnotes.com Vitamin H (Biotin) Source: Integrative Medicine Communications; www.drkoop.com
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CHAPTER 3. ALTERNATIVE MEDICINE AND MUSCULAR DYSTROPHY Overview In this chapter, we will begin by introducing you to official information sources on complementary and alternative medicine (CAM) relating to muscular dystrophy. 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 muscular dystrophy 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 “muscular dystrophy” (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 muscular dystrophy: •
A case of ventricular fibrillation in the prone position during back stabilisation surgery in a boy with Duchenne's muscular dystrophy. Author(s): Reid JM, Appleton PJ. Source: Anaesthesia. 1999 April; 54(4): 364-7. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10455837&dopt=Abstract
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Activity of creatine kinase in sera from healthy women, carriers of Duchenne muscular dystrophy and cord blood, determined by the “European” recommended method with NAC-EDTA activation. Author(s): Moss DW, Whitaker KB, Parmar C, Heckmatt J, Wikowski J, Sewry C, Dubowitz V.
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Source: Clinica Chimica Acta; International Journal of Clinical Chemistry. 1981 October 26; 116(2): 209-16. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=6794955&dopt=Abstract •
Actomyosin alterations in Duchenne muscular dystrophy. Author(s): Samaha FJ. Source: Archives of Neurology. 1973 June; 28(6): 405-7. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=4267103&dopt=Abstract
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Breathing exercises for children with pseudohypertrophic muscular dystrophy. Author(s): Houser CR, Johnson DM. Source: Physical Therapy. 1971 July; 51(7): 751-9. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=4933570&dopt=Abstract
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Ca2+ transport in erythrocytes from patients with Duchenne muscular dystrophy. Author(s): Pijst HL, Scholte HR. Source: Journal of the Neurological Sciences. 1983 August-September; 60(3): 411-7. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=6138395&dopt=Abstract
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Canadian pilot study in music therapy with muscular dystrophy children. Author(s): KORSON F. Source: Can J Occup Ther. 1959 June; 26(2): 45-9. No Abstract Available. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=13662904&dopt=Abstract
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Cell transplantation as an experimental treatment for Duchenne muscular dystrophy. Author(s): Law PK, Goodwin TG, Fang Q, Deering MB, Duggirala V, Larkin C, Florendo JA, Kirby DS, Li HJ, Chen M, et al. Source: Cell Transplantation. 1993 November-December; 2(6): 485-505. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=8167934&dopt=Abstract
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Clinical trial of high dosage vitamin E in human muscular dystrophy. Author(s): BERNESKE GM, BUTSON AR, GAULD EN, LEVY D. Source: Can Med Assoc J. 1960 February 20; 82: 418-21. No Abstract Available. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=13799736&dopt=Abstract
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Comparative effects of sodium selenite and selenomethionine upon nutritional muscular dystrophy, selenium-dependent glutathione peroxidase, and tissue selenium concentrations of turkey poults. Author(s): Cantor AH, Moorhead PD, Musser MA. Source: Poultry Science. 1982 March; 61(3): 478-84. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=7088800&dopt=Abstract
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Corticosteroids in Duchenne muscular dystrophy: a reappraisal. Author(s): Wong BL, Christopher C. Source: Journal of Child Neurology. 2002 March; 17(3): 183-90. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12026233&dopt=Abstract
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Cultural differences in family communication about Duchenne muscular dystrophy. Author(s): Fitzpatrick C, Barry C. Source: Developmental Medicine and Child Neurology. 1990 November; 32(11): 967-73. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=2269406&dopt=Abstract
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Deficiency of a 180-kDa extracellular matrix protein in Fukuyama type congenital muscular dystrophy skeletal muscle. Author(s): Sunada Y, Saito F, Higuchi I, Matsumura K, Shimizu T. Source: Neuromuscular Disorders : Nmd. 2002 February; 12(2): 117-20. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11738352&dopt=Abstract
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Dose-dependent effect of individualized respiratory muscle training in children with Duchenne muscular dystrophy. Author(s): Topin N, Matecki S, Le Bris S, Rivier F, Echenne B, Prefaut C, Ramonatxo M. Source: Neuromuscular Disorders : Nmd. 2002 August; 12(6): 576-83. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12117483&dopt=Abstract
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Duchenne muscular dystrophy and concomitant metastatic alveolar rhabdomyosarcoma. Author(s): Rossbach HC, Lacson A, Grana NH, Barbosa JL. Source: Journal of Pediatric Hematology/Oncology : Official Journal of the American Society of Pediatric Hematology/Oncology. 1999 November-December; 21(6): 528-30. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10598666&dopt=Abstract
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Duchenne muscular dystrophy--parental perceptions. Author(s): Bothwell JE, Dooley JM, Gordon KE, MacAuley A, Camfield PR, MacSween J. Source: Clinical Pediatrics. 2002 March; 41(2): 105-9. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11931326&dopt=Abstract
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Effects of electrical stimulation on muscles of children with Duchenne and Becker muscular dystrophy. Author(s): Zupan A, Gregoric M, Valencic V, Vandot S. Source: Neuropediatrics. 1993 August; 24(4): 189-92. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=8232775&dopt=Abstract
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Effects of iron deprivation on the pathology and stress protein expression in murine X-linked muscular dystrophy. Author(s): Bornman L, Rossouw H, Gericke GS, Polla BS.
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Source: Biochemical Pharmacology. 1998 September 15; 56(6): 751-7. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=9751080&dopt=Abstract •
Effects of physical therapy program on vital capacity of patients with muscular dystrophy. Author(s): Adams MA, Chandler LS. Source: Physical Therapy. 1974 May; 54(5): 494-6. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=4607793&dopt=Abstract
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Efficacy of drug regimen exceeds electrostimulation in treatment of avian muscular dystrophy. Author(s): Hudecki MS, Povoski SP, Gregorio CC, Granchelli JA, Pollina CM. Source: Journal of Applied Physiology (Bethesda, Md. : 1985). 1995 June; 78(6): 2014-9. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=7665393&dopt=Abstract
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Erythrocyte membrane autophosphorylation in Duchenne muscular dystrophy: effect of two methods of erythrocyte ghost preparation on results. Author(s): Roses AD. Source: Clinica Chimica Acta; International Journal of Clinical Chemistry. 1979 July 2; 95(1): 69-73. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=509731&dopt=Abstract
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Experimental and therapeutic approaches to muscular dystrophies. Author(s): Skuk D, Vilquin JT, Tremblay JP. Source: Current Opinion in Neurology. 2002 October; 15(5): 563-9. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12352000&dopt=Abstract
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Feasibility, safety, and efficacy of myoblast transfer therapy on Duchenne muscular dystrophy boys. Author(s): Law PK, Goodwin TG, Fang Q, Duggirala V, Larkin C, Florendo JA, Kirby DS, Deering MB, Li HJ, Chen M, et al. Source: Cell Transplantation. 1992; 1(2-3): 235-44. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=1344295&dopt=Abstract
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Hearing acuity in patients with muscular dystrophy. Author(s): Allen NR. Source: Developmental Medicine and Child Neurology. 1973 August; 15(4): 500-5. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=4732900&dopt=Abstract
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Hyperbaric oxygen therapy for muscular dystrophy. Author(s): Hirotani H, Kuyama T.
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Source: Nippon Geka Hokan. 1974 March; 43(2): 161-7. No Abstract Available. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=4473049&dopt=Abstract •
Inspiratory muscle training in patients with Duchenne muscular dystrophy. Author(s): Wanke T, Toifl K, Merkle M, Formanek D, Lahrmann H, Zwick H. Source: Chest. 1994 February; 105(2): 475-82. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=8306750&dopt=Abstract
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Muscle blood flow in Duchenne type muscular dystrophy, limb-girdle dystrophy, polymyositis, and in normal controls. Author(s): Paulson OB, Engel AG, Gomez MR. Source: Journal of Neurology, Neurosurgery, and Psychiatry. 1974 June; 37(6): 685-90. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=4210685&dopt=Abstract
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Muscular dystrophy: multidisciplinary approach to management. Author(s): Siegel IM. Source: Postgraduate Medicine. 1981 February; 69(2): 124-8, 131-3. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=7454643&dopt=Abstract
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Myotilin, the limb-girdle muscular dystrophy 1A (LGMD1A) protein, cross-links actin filaments and controls sarcomere assembly. Author(s): Salmikangas P, van der Ven PF, Lalowski M, Taivainen A, Zhao F, Suila H, Schroder R, Lappalainen P, Furst DO, Carpen O. Source: Human Molecular Genetics. 2003 January 15; 12(2): 189-203. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12499399&dopt=Abstract
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Na+ + K+ ATPase of erythrocyte membranes in Duchenne muscular dystrophy. Author(s): Mawatari S, Igisu H, Kuroiwa Y, Miyoshino S. Source: Neurology. 1981 March; 31(3): 293-7. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=6259557&dopt=Abstract
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Novel therapies for Duchenne muscular dystrophy. Author(s): Kapsa R, Kornberg AJ, Byrne E. Source: Lancet. Neurology. 2003 May; 2(5): 299-310. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12849184&dopt=Abstract
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Ocular muscular dystrophy. A cause of curare sensitivity. Author(s): Robertson JA. Source: Anaesthesia. 1984 March; 39(3): 251-3. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=6703294&dopt=Abstract
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Oral creatine supplementation in Duchenne muscular dystrophy: a clinical and 31P magnetic resonance spectroscopy study. Author(s): Felber S, Skladal D, Wyss M, Kremser C, Koller A, Sperl W. Source: Neurological Research. 2000 March; 22(2): 145-50. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10763500&dopt=Abstract
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Paraffin wax embedded muscle is suitable for the diagnosis of muscular dystrophy. Author(s): Sheriffs IN, Rampling D, Smith VV. Source: Journal of Clinical Pathology. 2001 July; 54(7): 517-20. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11429422&dopt=Abstract
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Pasteurella multocida pneumonia in an adolescent with Duchenne's muscular dystrophy following exposure to his helper dog. Author(s): Bacha F, Domachowske JB. Source: Clinical Pediatrics. 2001 March; 40(3): 159-61. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11307962&dopt=Abstract
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Progressive muscular dystrophy--Duchenne type. Controversies of the kinesitherapy treatment. Author(s): de Araujo Leitao AV, Duro LA, de Andrade Penque GM. Source: Rev Paul Med. 1995 September-October; 113(5): 995-9. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=8729744&dopt=Abstract
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Pulmonary problems in Duchenne muscular dystrophy. Diagnosis, prophylaxis, and treatment. Author(s): Siegel IM. Source: Physical Therapy. 1975 February; 55(2): 160-2. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=1096180&dopt=Abstract
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Pursed lips breathing improves ventilation in myotonic muscular dystrophy. Author(s): Ugalde V, Breslin EH, Walsh SA, Bonekat HW, Abresch RT, Carter GT. Source: Archives of Physical Medicine and Rehabilitation. 2000 April; 81(4): 472-8. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10768538&dopt=Abstract
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Pyruvic and lactic acid metabolism in muscular dystrophy, neuropathies and other neuromuscular disorders. Author(s): Goto I, Peters HA, Reese HH. Source: The American Journal of the Medical Sciences. 1967 April; 253(4): 431-48. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=4290040&dopt=Abstract
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Relating familial stress to the psychosocial adjustment of adolescents with Duchenne muscular dystrophy. Author(s): Reid DT, Renwick RM.
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Source: International Journal of Rehabilitation Research. Internationale Zeitschrift Fur Rehabilitationsforschung. Revue Internationale De Recherches De Readaptation. 2001 June; 24(2): 83-93. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11421396&dopt=Abstract •
Report on the muscular dystrophy campaign workshop: exercise in neuromuscular diseases Newcastle, January 2002. Author(s): Eagle M. Source: Neuromuscular Disorders : Nmd. 2002 December; 12(10): 975-83. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12467755&dopt=Abstract
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Respiratory muscle training in Duchenne muscular dystrophy. Author(s): Rodillo E, Noble-Jamieson CM, Aber V, Heckmatt JZ, Muntoni F, Dubowitz V. Source: Archives of Disease in Childhood. 1989 May; 64(5): 736-8. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=2658856&dopt=Abstract
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Respiratory muscle training in Duchenne muscular dystrophy. Author(s): Smith PE, Coakley JH, Edwards RH. Source: Muscle & Nerve. 1988 July; 11(7): 784-5. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=3405245&dopt=Abstract
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Reversal of impaired oxidative phosphorylation and calcium overloading in the in vitro cardiac mitochondria of CHF-146 dystrophic hamsters with hereditary muscular dystrophy. Author(s): Bhattacharya SK, Johnson PL, Thakar JH. Source: Journal of the Neurological Sciences. 1993 December 15; 120(2): 180-6. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=8138808&dopt=Abstract
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Selenium metabolism and supplementation in patients with muscular dystrophy. Author(s): Jackson MJ, Coakley J, Stokes M, Edwards RH, Oster O. Source: Neurology. 1989 May; 39(5): 655-9. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=2540451&dopt=Abstract
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Selenium supplementation in X-linked muscular dystrophy. Effects on erythrocyte and serum selenium and on erythrocyte glutathione peroxidase activity. Author(s): Gebre-Medhin M, Gustavson KH, Gamstorp I, Plantin LO. Source: Acta Paediatr Scand. 1985 November; 74(6): 886-90. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=4090964&dopt=Abstract
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Spectrin extractability from erythrocytes in Duchenne muscular dystrophy patients and carriers and in other myopathies.
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Author(s): Gargioni G, Chiaffoni G, Bonadonna G, Corradini P, Lechi C, de Grandis D, Zatti M. Source: Clinica Chimica Acta; International Journal of Clinical Chemistry. 1985 February 15; 145(3): 259-65. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=3987029&dopt=Abstract •
Therapies in muscular dystrophy: current concepts and future prospects. Author(s): Urtizberea JA. Source: European Neurology. 2000; 43(3): 127-32. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10765050&dopt=Abstract
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Update on Duchenne muscular dystrophy. Author(s): Siegel IM. Source: Compr Ther. 1989 March; 15(3): 45-52. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=2650976&dopt=Abstract
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Use of child's kapok life preserver in reversed position in rehabilitation of children with pseudohypertrophic muscular dystrophy. Author(s): PIERCE DS. Source: Archives of Physical Medicine and Rehabilitation. 1962 November; 43: 574-5. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=13943395&dopt=Abstract
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Weaning from mechanical ventilation: successful use of modified inspiratory resistive training in muscular dystrophy. Author(s): Aldrich TK, Uhrlass RM. Source: Critical Care Medicine. 1987 March; 15(3): 247-9. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=3816259&dopt=Abstract
Additional Web Resources A number of additional Web sites offer encyclopedic information covering CAM and related topics. The following is a representative sample: •
Alternative Medicine Foundation, Inc.: http://www.herbmed.org/
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AOL: http://search.aol.com/cat.adp?id=169&layer=&from=subcats
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Chinese Medicine: http://www.newcenturynutrition.com/
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drkoop.com: http://www.drkoop.com/InteractiveMedicine/IndexC.html
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Family Village: http://www.familyvillage.wisc.edu/med_altn.htm
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Google: http://directory.google.com/Top/Health/Alternative/
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Healthnotes: http://www.healthnotes.com/
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MedWebPlus: http://medwebplus.com/subject/Alternative_and_Complementary_Medicine
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Open Directory Project: http://dmoz.org/Health/Alternative/
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HealthGate: http://www.tnp.com/
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WebMDHealth: http://my.webmd.com/drugs_and_herbs
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WholeHealthMD.com: http://www.wholehealthmd.com/reflib/0,1529,00.html
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Yahoo.com: http://dir.yahoo.com/Health/Alternative_Medicine/
The following is a specific Web list relating to muscular dystrophy; 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 Dysphagia Source: Integrative Medicine Communications; www.drkoop.com Muscular dystrophy Source: Integrative Medicine Communications; www.drkoop.com Muscular Dystrophy Source: Integrative Medicine Communications; www.drkoop.com Swallowing, Difficulty Source: Integrative Medicine Communications; www.drkoop.com
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Alternative Therapy Trager approach Source: WholeHealthMD.com, LLC. www.wholehealthmd.com Hyperlink: http://www.wholehealthmd.com/refshelf/substances_view/0,1525,741,00.html
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Herbs and Supplements Allopurinol Source: Healthnotes, Inc. www.healthnotes.com BCAAs Source: Prima Communications, Inc.www.personalhealthzone.com Coenzyme Q10 Source: Healthnotes, Inc. www.healthnotes.com Coenzyme Q10 Source: Integrative Medicine Communications; www.drkoop.com
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Coenzyme Q10 (CoQ10) Source: Prima Communications, Inc.www.personalhealthzone.com CoQ10 Source: Integrative Medicine Communications; www.drkoop.com Glycyrrhiza1 Alternative names: Licorice; Glycyrrhiza glabra L. Source: Alternative Medicine Foundation, Inc. www.amfoundation.org
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 MUSCULAR DYSTROPHY Overview In this chapter, we will give you a bibliography on recent dissertations relating to muscular dystrophy. 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 “muscular dystrophy” (or a synonym) in their titles. To accurately reflect the results that you might find while conducting research on muscular dystrophy, we have not necessarily excluded non-medical dissertations in this bibliography.
Dissertations on Muscular Dystrophy 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 muscular dystrophy. You will see that the information provided includes the dissertation’s title, its author, and the institution with which the author is associated. The following covers recent dissertations found when using this search procedure: •
A Descriptive Analysis of 'the Jerry Lewis Labor Day Telethon for Muscular Dystrophy'. by Londino, Lawrence Joseph, Phd from The University of Michigan, 1978, 209 pages http://wwwlib.umi.com/dissertations/fullcit/7907126
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A Study of Natural Killer Cells in Murine Muscular Dystrophy by Semple, John Wesley; Phd from Queen's University at Kingston (canada), 1986 http://wwwlib.umi.com/dissertations/fullcit/NL30415
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A Study of Selected Variables in Relation to Accidents of Muscular Dystrophy Children in Special Schools. by Nemarich, Samuel Peter, Phd from New York University, 1975, 168 pages http://wwwlib.umi.com/dissertations/fullcit/7601746
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Aav-mediated Gene Transfer to Models of Muscular Dystrophy: Insights into Assembly of Multi-subunit Membrane Proteins by Dressman, Devin Charles; Phd from University of Pittsburgh, 2002, 173 pages http://wwwlib.umi.com/dissertations/fullcit/3068706
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Abnormal Sodium Channel Gating in Murine Cardiac Myocytes Deficient in Myotonic Dystrophy Protein Kinase by Lee, Hwa Chun; Phd from University of Virginia, 2002, 120 pages http://wwwlib.umi.com/dissertations/fullcit/3044884
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Adenoviral Vectors for Treatment of Duchenne Muscular Dystrophy by Hartigano'connor, Dennis Joseph; Phd from University of Michigan, 2003, 158 pages http://wwwlib.umi.com/dissertations/fullcit/3079456
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Biochemical Studies Related to Lipid Metabolism in Muscular Dystrophy by Jatorodriguez, Juan Jose; Phd from The University of Western Ontario (canada), 1972 http://wwwlib.umi.com/dissertations/fullcit/NK11997
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Biochemical Studies Related to the Progression of Muscular Dystrophy in the Umx7.1 Syrian Hamster by Klamut, Henry Joseph; Phd from The University of Western Ontario (canada), 1986 http://wwwlib.umi.com/dissertations/fullcit/NL33047
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Contraction-induced Muscle Damage in Dogs with Golden Retriever Muscular Dystrophy by Childers, Martin Kent; Phd from University of Missouri - Columbia, 2002, 161 pages http://wwwlib.umi.com/dissertations/fullcit/3074385
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Control of Brown Adipose Tissue Growth and Function in Rats and Hamsters Normalities in Genetic Models of Human Disease (obesity Muscular Dystrophy) by Triandafillou, Joan; Phd from University of Ottawa (canada), 1985 http://wwwlib.umi.com/dissertations/fullcit/NK65634
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Development and Characterization of a Cell Culture Model of the Myotonic Dystrophy Trinucleotide (ctg) Repeat Expansion Mutation by Amack, Jeffrey Dillon; Phd from The University of Wisconsin - Madison, 2002, 173 pages http://wwwlib.umi.com/dissertations/fullcit/3060418
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Development of Methods to Study the Acetylcholine Receptor in Murine Muscular Dystrophy Its Assay, Activity and Concentration by Kruck, Theo P. A; Phd from York University (canada), 1983 http://wwwlib.umi.com/dissertations/fullcit/NK61490
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Duchenne Muscular Dystrophy Genetic and Biochemical Studies of the Female Carriers and Their Families by Hutton, Elaine M. Edwards; Advdeg from University of Toronto (canada), 1970 http://wwwlib.umi.com/dissertations/fullcit/NK09148
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Energy Metabolism in Progressive Muscular Dystrophy Studies on Oxidative Phosphorylation of Genetically Determined Muscular Dystrophy in Mice and Hamsters by Wrogemann, Klaus; Advdeg from The University of Manitoba (canada), 1969 http://wwwlib.umi.com/dissertations/fullcit/NK04482
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Examining the Repressive Nature of D4z4 Repeats and Their Role in the Pathogenesis of Facioscapulohumeral Muscular Dystrophy by Yip, Darren J. Msc from University of Ottawa (canada), 2002, 124 pages http://wwwlib.umi.com/dissertations/fullcit/MQ76651
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Experimental Manipulation Which Interferes with the Phenotypic Expression of the Dystrophic Process Cross Reinnervation of a Fast Twitch Muscle by the Nerve of a Slow Tonic Muscle in Chickens with Hereditary Muscular Dystrophy by Mazliah, Jacob; Phd from Mcmaster University (canada), 1981 http://wwwlib.umi.com/dissertations/fullcit/NK52268
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Experimental Manipulation Which Results in the Phenotypic Expression of the Dystrophic Process Cross-reinnervation of a Slow Tonic Muscle by the Nerve of a Fast Twitch Muscle in Chickens with Hereditary Muscular Dystrophy by Gandy, Alan Clarke; Phd from Mcmaster University (canada), 1986 http://wwwlib.umi.com/dissertations/fullcit/NL33439
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Formation and Control of Trajectory during Multijoint Arm Movements in Duchenne's Muscular Dystrophy by Bowen, Roscoe Clint; Phd from Drexel University, 2003, 126 pages http://wwwlib.umi.com/dissertations/fullcit/3086398
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Functional Evaluation of the Reversibility of Muscular Dystrophy in the Mdx Mouse Via Dystrophin Restoration by Dellorusso, Christiana; Phd from University of Michigan, 2002, 148 pages http://wwwlib.umi.com/dissertations/fullcit/3042062
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Maximal Isometric Strength on the Kinetic Communicator System for Duchenne Muscular Dystrophy Patients by Xie, Xiaoqing (steven); Da from Middle Tennessee State University, 2001, 123 pages http://wwwlib.umi.com/dissertations/fullcit/3030580
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Neurotrophism in Mouse Muscular Dystrophy by Law, Peter Koi; Phd from University of Toronto (canada), 1972 http://wwwlib.umi.com/dissertations/fullcit/NK15399
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Nitric Oxide Function in Dystrophin-deficient Muscular Dystrophy by Henricks, Michelle; Phd from University of California, Los Angeles, 2002, 110 pages http://wwwlib.umi.com/dissertations/fullcit/3040234
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Parents' Perspectives on Duchenne/becker Muscular Dystrophy and Specific Learning Disabilities: a Grounded Theory Study by Webb, Carol Lee; Phd from Ohio University, 2002, 170 pages http://wwwlib.umi.com/dissertations/fullcit/3062177
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Partial Characterization of Cholesterol Metabolism in Fast-glycolytic Muscle from Mice with Hereditary Muscular Dystrophy by Kuhn, Donald E; Phd from York University (canada), 1988 http://wwwlib.umi.com/dissertations/fullcit/NL45888
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Roles for the Proteoglycan Biglycan in Muscular Dystrophy and Neuromuscular Junction Formation by Rafii, Michael S. Phd from Brown University, 2002, 271 pages http://wwwlib.umi.com/dissertations/fullcit/3050955
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Structural Flexibilty of the Dystrophin Rod Domain: Implications for Gene Therapy of Duchenne Muscular Dystrophy Using Adeno-associated Viral Vectors by Harper, Scott Quenton; Phd from University of Michigan, 2002, 158 pages http://wwwlib.umi.com/dissertations/fullcit/3057958
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The Effect of Physostigmine on Language Processes in Boys with Duchenne Muscular Dystrophy (memory) by Cameron, Thomas Hartley, Phd from The University of North Carolina at Chapel Hill, 1985, 108 pages http://wwwlib.umi.com/dissertations/fullcit/8527184
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Tracking the Pathophysiology of Duchenne Muscular Dystrophy (dmd) with Functional Proteomics by Ge, Yue; Phd from University of Michigan, 2002, 144 pages http://wwwlib.umi.com/dissertations/fullcit/3068867
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Ultrastructure of Muscle in Typical and Atypical Duchenne Muscular Dystrophy: a Comparative Study by Oteruelo, Félix Teodoro; Phd from The University of Western Ontario (canada), 1972 http://wwwlib.umi.com/dissertations/fullcit/NK12009
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. DYSTROPHY
CLINICAL
TRIALS
AND
MUSCULAR
Overview In this chapter, we will show you how to keep informed of the latest clinical trials concerning muscular dystrophy.
Recent Trials on Muscular Dystrophy The following is a list of recent trials dedicated to muscular dystrophy.8 Further information on a trial is available at the Web site indicated. •
A multicenter randomized placebo-controlled double-blind study to assess efficacy and safety of glutamine and creatine monohydrate in Duchenne muscular dystrophy (DMD) Condition(s): Muscular Dystrophy, Duchenne Study Status: This study is currently recruiting patients. Sponsor(s): National Center for Research Resources (NCRR); Children's National Medical Center Purpose - Excerpt: To establish a collaborative group of clinical trial centers, with standardized equipment and protocols, able to conduct both drug and gene therapy trials in DMD. To evaluate the therapeutic effect of glutamine and creatine monohydrate on muscle strength in children with DMD. To validate the use of QMT (quantitative muscle strength testing) and gait analysis in children with DMD as reliable tools to quantify muscle strength, monitor disease progression and assess therapeutic response. Phase(s): Phase III Study Type: Interventional Contact(s): see Web site below Web Site: http://clinicaltrials.gov/ct/show/NCT00018109
8
These are listed at www.ClinicalTrials.gov.
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An open-label pilot study of Coenzyme Q10 in steroid-treated Duchenne muscular dystrophy Condition(s): Muscular Dystrophy, Duchenne Study Status: This study is currently recruiting patients. Sponsor(s): Cooperative International Neuromuscular Research Group Purpose - Excerpt: This study will help to determine the safety and efficacy of the nutritional supplement Coenzyme Q10 when added to steroids as a treatment for Duchenne muscular dystrophy (DMD). Boys with DMD who are enrolled in this study will should be on a stable dose of steroids for at least six months, and will remain on their usual dose throughout the study. They will complete two screening visits within a one-week period, and if enrolled will then have their strength tested monthly for three months before beginning therapy with Coenzyme Q10. Once Coenzyme Q10 therapy is started, participants will have their strength tested monthly for six months. Following the six month treatment period, participants will be given the option to remain on Coenzyme Q10 until the study is completed. Phase(s): Phase II Study Type: Interventional Contact(s): see Web site below Web Site: http://clinicaltrials.gov/ct/show/NCT00033189
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KUL0401: An open-label pilot study of Oxatomide in steroid-naive Duchenne muscular dystrophy Condition(s): Muscular Dystrophy, Duchenne Study Status: This study is currently recruiting patients. Sponsor(s): Cooperative International Neuromuscular Research Group Purpose - Excerpt: This study will help to determine the safety and efficacy of the mast cell stabilizer Oxatomide as a treatment for Duchenne muscular dystrophy (DMD). Boys with DMD who are enrolled in this study will should not have taken steroids to treat DMD for at least twelve months, and should not have taken any nutritional supplements for at least three months. Subjects will complete a two screening visits within a one-week period, and if enrolled will then have their strength tested monthly for three months before beginning therapy with Oxatomide. Once Oxatomide therapy is started, participants will have their strength tested monthly for six months. Following the six month treatment period, participants will be given the option to remain on Oxatomide until the study is completed. Phase(s): Phase II Study Type: Interventional Contact(s): see Web site below Web Site: http://clinicaltrials.gov/ct/show/NCT00033813
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Study of Albuterol and Oxandrolone in Patients With Facioscapulohumeral Dystrophy (FSHD) Condition(s): Muscular Dystrophies Study Status: This study is currently recruiting patients.
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Sponsor(s): FDA Office of Orphan Products Development Purpose - Excerpt: This is a study to determine whether albuterol or oxandrolone, alone or in combination, are able to increase strength and muscle mass in patients with FSHD. It also will determine if albuterol given in "pulsed" fashion will have more effect than when given continuously. Study Type: Interventional Contact(s): see Web site below Web Site: http://clinicaltrials.gov/ct/show/NCT00027391 •
Study of Inherited Neurological Disorders Condition(s): Ataxia; Motor Neuron Disease; Muscular Disease; Muscular Dystrophy; Peripheral Nervous System Disease Study Status: This study is currently recruiting patients. Sponsor(s): National Institute of Neurological Disorders and Stroke (NINDS) Purpose - Excerpt: This study is designed to learn more about the natural history of inherited neurological disorders and the role of heredity in their development. It will examine the genetics, symptoms, disease progression, treatment, and psychological and behavioral impact of diseases in the following categories: hereditary peripheral neuropathies; hereditary myopathies; muscular dystrophies; hereditary motor neuron disorders; mitochondrial myopathies; ataxias; hereditary neurocognitive disorders; inherited neurological disorders without known diagnosis; and others. Many of these diseases, which affect the brain, spinal cord, muscles, and nerves, are rare and poorly understood. Children and adults of all ages with various inherited neurological disorders may be eligible for this study. Participants will undergo a detailed medical and family history, and a family tree will be drawn. They will also have a physical and neurological examination that may include blood test and urine tests, an EEG (brain wave recordings), psychological tests, and speech and language and rehabilitation evaluations. A blood sample or skin biopsy may be taken for genetic testing. Depending on the individual patient's symptoms, imaging tests such as X-rays, CT or MRI scans and muscle and nerve testing may also be done. Information from this study may provide a better understanding of the genetic underpinnings of these disorders, contributing to improved diagnosis, treatment, and genetic counseling, and perhaps leading to additional studies in these areas. Study Type: Observational Contact(s): see Web site below Web Site: http://clinicaltrials.gov/ct/show/NCT00004568
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Creatine and Glutamine in Steroid-Naive Duchenne Muscular Dystrophy Condition(s): Muscular Dystrophy, Duchenne Study Status: This study is no longer recruiting patients. Sponsor(s): Cooperative International Neuromuscular Research Group Purpose - Excerpt: This study will help to determine the effectiveness of glutamine and creatine as a possible therapy for DMD. Boys with DMD who are enrolled in this trial will be randomly chosen to receive creatine monohydrate or glutamine or an inactive placebo orally for six months. Once a month during the six-month treatment period, the study participants will have their muscle strength evaluated using manual and
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computerized testing methods. This study will be conducted at several CINRG Centers throughout the U.S., Belgium, Israel and Puerto Rico. This study is supported by the Muscular Dystrophy Association. Phase(s): Phase II; Phase III Study Type: Interventional Contact(s): see Web site below Web Site: http://clinicaltrials.gov/ct/show/NCT00016653 •
Randomized Study of Albuterol in Patients with Facioscapulohumeral Muscular Dystrophy Condition(s): Muscular Dystrophy, Facioscapulohumeral Study Status: This study is no longer recruiting patients. Sponsor(s): FDA Office of Orphan Products Development; Ohio State University Purpose - Excerpt: Objectives: I. Determine whether albuterol increases strength in patients with facioscapulohumeral dystrophy as measured by quantitative voluntary isometric contraction testing. II. Determine whether albuterol increases muscle mass in this patient population as determined by 24 hour urinary creatinine excretion and dual energy x-ray absorptiometry (DEXA). III. Examine the long term safety of albuterol in this patient population. Study Type: Interventional Contact(s): see Web site below Web Site: http://clinicaltrials.gov/ct/show/NCT00004685
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Gentamicin Treatment of Muscular Dystrophy Condition(s): Becker muscular dystrophy; Duchenne muscular dystrophy Study Status: This study is completed. Sponsor(s): National Institute of Neurological Disorders and Stroke (NINDS) Purpose - Excerpt: This study will evaluate the antibiotic gentamicin for treating patients with muscular dystrophy caused by a specific genetic abnormality known as a nonsense mutation. In studies of mice with this type of muscular dystrophy, gentamicin treatment produced positive changes in muscle tissue. Patients with Duchenne or Becker muscular dystrophy caused by nonsense mutations by may be eligible for this 2week study. Before starting treatment, patients will have evaluations of muscle strength and general well being. Two muscle tissue samples will be taken by needle biopsy, under local anesthetic and sedation. Because of potential risks of hearing loss and kidney toxicity associated with gentamicin, patients will also have a hearing test and blood and urine tests for kidney function before starting treatment. (Currently, gentamicin is commonly prescribed for serious infections of the lungs, heart, and digestive and urinary tracts; adverse effects of hearing loss and kidney toxicity can occur with excessively high drug doses.) Patients will be hospitalized during drug treatment. Gentamicin will be given intravenously (through a vein) once a day for 14 days. Blood samples will be collected daily to monitor drug levels and determine dosage adjustments, if necessary. Urine samples will be collected to assess kidney function. Hearing tests will be done on days 7 and 10. On the last day of the study, hearing, kidney function, and muscle strength will be tested and the results compared with pretreatment levels. Blood and muscle samples will also be taken again for pre-treatment
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comparison. Hearing, blood, urine, and muscle strength tests will be repeated one month after treatment ends for comparison with previous results. Phase(s): Phase I Study Type: Interventional Contact(s): see Web site below Web Site: http://clinicaltrials.gov/ct/show/NCT00005574 •
Phase III Randomized, Double-Blind Study of Prednisone for Duchenne Muscular Dystrophy Condition(s): Duchenne Muscular Dystrophy Study Status: This study is completed. Sponsor(s): National Center for Research Resources (NCRR); National Institute of Neurological Disorders and Stroke (NINDS); University of Rochester Purpose - Excerpt: Objectives: I. Characterize the effect of prednisone on muscle protein metabolism in patients with Duchenne muscular dystrophy. II. Determine whether prednisone changes levels of insulin-like growth factor 1, growth hormone, and insulin. III. Characterize the effect of prednisone on muscle morphometry and muscle localization of utrophin. IV. Compare the prednisone response in patients with Duchenne muscular dystrophy to that seen in normal individuals and in patients with facioscapulohumeral dystrophy. Phase(s): Phase III Study Type: Interventional Contact(s): see Web site below Web Site: http://clinicaltrials.gov/ct/show/NCT00004646
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Studies of Patients with Skin Disease, Patients with Neurological Degenerations, and Normal Volunteers Condition(s): Healthy; Muscular Dystrophy; Retinal Degeneration; Skin Diseases; Virus Diseases Study Status: This study is completed. Sponsor(s): National Cancer Institute (NCI) Purpose - Excerpt: It is proposed that patients with skin disease due to presumed immunologic, genetic or viral-induced abnormalities, patients with neurological degenerations, and normal controls be evaluated with various in vitro studies of immunologic, genetic, and virologic function. This is to include studies of peripheral blood (cells and serum) as well as studies of skin obtained with a biopsy instrument. In addition, studies of gastrointestinal function will be performed where appropriate. Study Type: Observational Contact(s): see Web site below Web Site: http://clinicaltrials.gov/ct/show/NCT00001164
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Study of Muscle Wasting and Altered Metabolism in Patients with Myotonic Dystrophy Condition(s): Muscular Dystrophy
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Study Status: This study is completed. Sponsor(s): National Center for Research Resources (NCRR); University of Rochester Purpose - Excerpt: Objectives: I. Examine the interrelationships between muscle wasting (phenotype), the degree of myotonic dystrophy (DM) gene expression (genotype) in patients with DM. II. Characterize the insulin resistance in these patients. III. Assess the glucose uptake in the leg and forearm tissues of these patients. IV. Determine the stability of the DM gene lesion in muscles over a 5-10 year period. Study Type: Observational Contact(s): see Web site below Web Site: http://clinicaltrials.gov/ct/show/NCT00004769
Keeping Current on Clinical Trials The U.S. National Institutes of Health, through the National Library of Medicine, has developed ClinicalTrials.gov to provide current information about clinical research across the broadest number of diseases and conditions. The site was launched in February 2000 and currently contains approximately 5,700 clinical studies in over 59,000 locations worldwide, with most studies being conducted in the United States. ClinicalTrials.gov receives about 2 million hits per month and hosts approximately 5,400 visitors daily. To access this database, simply go to the Web site at http://www.clinicaltrials.gov/ and search by “muscular dystrophy” (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 MUSCULAR DYSTROPHY 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 “muscular dystrophy” (or a synonym) in their titles. To accurately reflect the results that you might find while conducting research on muscular dystrophy, we have not necessarily excluded non-medical patents in this bibliography.
Patents on Muscular Dystrophy By performing a patent search focusing on muscular dystrophy, 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 muscular dystrophy: •
Changes in laminin subunit composition are diagnostic of Fukuyama congenital muscular dystrophy Inventor(s): Engvall; Eva (Rancho Santa Fe, CA), Arahata; Kiichi (Tokyo, JP) Assignee(s): La Jolla Cancer Research Foundation (La Jolla, CA) Patent Number: 5,780,244 Date filed: February 14, 1994 Abstract: The present invention relates to a method for detecting altered expression or localization of a cytoskeleton/basal lamina protein in a tissue sample obtained from an individual, wherein the altered expression or localization are associated with a muscular dystrophy such as Fukuyama congenital muscular dystrophy (FCMD). The invention provides an immunohistochemical method for detecting the expression and localization in a tissue, such as muscle, of laminin M (merosin), which is a protein component of the basal lamina, wherein certain defined changes are diagnostic of individuals predisposed to FCMD. The invention also provides a prenatal diagnostic screening procedure, using a tissue such as placenta, wherein the screening procedure can identify an individual predisposed to FCMD. The invention further provides methods for identifying an individual predisposed to other muscular dystrophies such as Walker-Warburg Syndrome (WWS) and muscle-eye-brain disease of the Finnish type (MEB). Excerpt(s): This invention relates generally to the field of medicine and more specifically to methods for detecting changes in the expression of laminin M protein and of M chain mRNA that are diagnostic of Fukuyama congenital muscular dystrophy (FCMD). The invention further relates to methods of identifying agents that can reduce or prevent the symptoms associated with FCMD and to methods of treating an FCMD patient. The basal lamina of muscle fibers is a specialized extracellular matrix that has a static structure that contributes to the proper migration, proliferation and regeneration of myogenic cells during development or after injury or tissue grafting (Alberts et al., Molecular Biology of the Cell (Garland Publ., Inc. 1989); Sanes et al., Myology (McGrawHill Book Co., NY, 1986); Martin, G. R., Ann. Rev. Cell Biol. 3:37-85 (1987); Alameddine et al., Neuromusc. Dis. 1:143-152 (1991)). The components of the basal lamina include laminin, type IV collagen, fibronectin and heparan-sulfate proteoglycan. The large laminin protein, which has a molecular weight of approximately 850 kilodaltons (kdal), is a heterotrimer consisting of two smaller chains (B1, S or B2) and one larger chain (A or M) which are arranged in the shape of a cross. Thus, laminin trimers have various structures such as A-B1-B2, M-B1-B2, A-S-B2 and M-S-B2. Other laminins such as kalinin and K-laminin contain an A chain homolog, designated K (Marinkovich et al., J. Cell Biol. 119:695-703 (1992). Laminin is found adjacent to the plasma membrane of muscle fibers, where its multiple functional domains bind type IV collagen, proteoglycans and laminin receptor proteins, such as integrins (Hynes and Lander, Cell 68:303-322 (1992)) and the 156 kdal dystrophin-associated glycoprotein (DAG) (Ibraghimov-Beskrovnaya et al., Nature 355:696-702 (1992)), which are present on the plasma membrane of the muscle fibers. The various laminin isoforms can be either ubiquitously expressed or tissue-specific (Leivo and Engvall, Proc. Natl. Acad. Sci. USA 85:1544-1548 (1988); Ehrig et al., Proc. Natl. Acad. Sci. USA 87:3264-3268 (1990); Sanes et al., J. Cell Biol. 111:16851699 (1990)). For example, laminin M (merosin) contains an M chain subunit that is specific for striated muscle, Schwann cells and trophoblast, where it replaces the "A"
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subunit in the ubiquitous non-muscle laminin polyprotein (Leivo and Engvall (1988); Wewer et al., Lab. Invest. 66:378-389 (1992)). Web site: http://www.delphion.com/details?pn=US05780244__ •
Diagnosis of autosomal muscular dystrophy Inventor(s): Campbell; Kevin P. (Iowa City, IA), Matsumura; Kiichiro (Iowa City, IA) Assignee(s): Univ. of Iowa Research Foundation (Oakdale, IA) Patent Number: 5,308,752 Date filed: September 14, 1992 Abstract: Disclosed are methods for the diagnosis of autosomal muscular dystrophy through the analysis of muscle tissue using antibodies reactive with components of the dystrophin-glycoprotein complex. An experimental muscle tissue sample, treated if necessary to render components of the dystrophin-glycoprotein complex available for antibody binding, is contacted with an antibody which binds to a dystrophin-associated protein. The extent of antibody binding is determined, and compared to the extent of antibody binding to normal control tissue. A substantial reduction in the extent of binding to experimental tissue, as compared with normal control tissue, being diagnostic of autosomal muscular dystrophy. Among the autosomal muscular dystrophies which are detectable by the methods described herein are Fukuyama muscular dystrophy and severe childhood autosomal recessive muscular dystrophy. Excerpt(s): Severe childhood autosomal recessive muscular dystrophy (SCARMD) is a disease which is prevalent in North Africa. This progressive muscular dystrophy shares several clinical features with Duchenne's muscular dystrophy (DMD) including, for example, mode of onset, rapid progression, hypertrophy of calves and extremely high serum creatine kinase levels during the initial stages of the disease (see, e.g., Ben Hamida et al., J. Neurol Sci. 107: 60-64 (1992)). It has been demonstrated that Duchenne's muscular dystrophy is caused by a mutation or deletion which results in the absence of the dystrophin protein (Hoffman et al., Cell 51: 919-928 (1987)). Dystrophin has been shown to be associated with a large oligomeric complex of sarcolemmal glycoproteins (see, e.g., Ervasti and Campbell, Cell 66: 1121-1131 (1991)). The dystrophin-glycoprotein complex has been proposed to span the sarcolemma and provide a linkage between the subsarcolemmal cytoskeleton and the extracellular matrix. In DMD, the absence of dystrophin leads to a great reduction in all of the dystrophin-associated proteins. These observations have enabled, for example, the development of immunologically-based methods for the diagnosis of DMD. In contrast to DMD, it has been reported that dystrophin and dystrophin-related protein (DRP), an autosomal homologue of dystrophin, are expressed normally in the skeletal muscle of individuals afflicted with SCARMD (see, e.g., Khurana et al., Neuromusc. Dis. 1: 185-194 (1991)). Thus, there is no teaching in the prior art which would enable the development of an immunologicallybased method for diagnosing SCARMD, or other autosomal muscular dystrophies. Web site: http://www.delphion.com/details?pn=US05308752__
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Diagnosis of myotonic muscular dystrophy Inventor(s): Fu; Ying-Hui (Columbus, OH), Caskey; C. Thomas (West University, TX), Fenwick; Raymond G. (Sugarland, TX), Friedman; David L. (Houston, TX), Pizzuti; Antonio (Milan, IT) Assignee(s): Baylor College of Medicine (Houston, TX) Patent Number: 5,552,282 Date filed: June 6, 1993 Abstract: The present invention includes a DNA clone from the myotonic muscular dystrophy gene, a cosmid probe to the myotonic dystrophy site, as well as methods of detecting myotonic muscular dystrophy using RFLP. The method involves the steps of digesting DNA from an individual to be tested with a restriction endonuclease and detecting the restriction fragment length polymorphism with hybridization to probes within the myotonic muscular locus and southern blot analysis. Alternatively, the myotonic muscular dystrophy gene can be measured by determining the amount of mRNA or measuring the amount of protein with an antibody. Further, the myotonic muscular dystrophy gene defect can be detected using either fluorescence in situ hybridization or pulsed field gel electrophoresis using the probes described herein. Excerpt(s): This invention relates to the field of molecular diagnosis of myotonic muscular dystrophy. The myotonic muscular dystrophy (DM) disease is the most common adult muscular dystrophy in man with a prevalence of 1 in 10,000. The disorder is inherited in an autosomal dominant manner with variable expression of symptoms from individual to individual within a given family. Furthermore, the phenomenon of anticipation (increasing disease severity over generations) is well documented for DM. This is particularly evident when an affected mother transmits the gene for the disease to her offspring. These offspring have a high incidence of mental retardation and profound infantile myotonia. Adult patients with DM manifest a pleiotropic set of symptoms including myotonia, cardiac arrhythmias, cataracts, frontal baldness, hypogonadism, and other endocrine dysfunctions. There is no evidence that myotonic muscular dystrophy may be caused by defects in more than one gene. A myotonic muscular dystrophy gene has been mapped to human chromosome position 19q13.3. Both a genetic and physical map of the region was developed by a group of investigators acting as a voluntary consortium under sponsorship of the Muscular Dystrophy Association. The genetic linkage studies identified two RFLP alleles, D10 and X75, which are polymerase chain reaction (PCR)-based dinucleotide polymorphisms and are tightly linked to DM. Web site: http://www.delphion.com/details?pn=US05552282__
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DNA sequence encoding the myotonic dystrophy gene and uses thereof Inventor(s): Johnson; Keith J. (Glasgow, GB), Harley; Helen G. (Rhiwbina, GB), Shaw; Duncan J. (Banchory, GB), Housman; David E. (Newton, MA), Brook; J. David (West Bridgford, GB) Assignee(s): University of Wales College of Medicine (Cardiff, GB), Massachusetts Institute of Technology (Cambridge, MA) Patent Number: 5,977,333 Date filed: April 14, 1995
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Abstract: A nucleotide sequence, specifically a CTG triplet repeat, is shown to be expanded in individuals affected with myotonic dystrophy and can be identified in a sample obtained from an individual. Individuals in whom the CTG triplet repeat is present in normal copy number are likely to be minimally affected and individuals in whom the CTG triplet repeat occurs in abnormally high copy number are likely to be more severely affected. Excerpt(s): Myotonic dystrophy (DM) is an autosomal dominant neuromuscular disease with an estimated minimum incidence of 1 in 8000 (Harper, P. S., Myotonic Dystrophy, 2nd ed., W. B. Saunders Co., London, 1989). It is the most common form of muscular dystrophy affecting adults. The clinical picture in DM is well established but exceptionally variable (Harper, P. S., Myotonic Dystrophy, 2nd ed., W. B. Saunders Co., London, 1989). Although generally considered a disease of muscle, with myotonia, progressive weakness and wasting, DM is characterized by abnormalities in a variety of other systems. DM patients often suffer from cardiac conduction defects, smooth muscle involvement, hypersomnia, cataracts, abnormal glucose response, and, in males, premature balding and testicular atrophy (Harper, P. S., Myotonic Dystrophy, 2nd ed., W. B. Saunders Co., London, 1989). One of the striking features of this disorder is the variability of phenotype, both within and between families. For clinical purposes, patients are often subdivided into three groups according to the clinical syndrome and age at onset of the disorder (Harper, P. S. and Dyken, P. R., Lancet, 2:53-55 (1972)). The mildest form, which is occasionally difficult to diagnose, is seen in middle or old age and is characterized by cataracts with little or no muscle involvement. The classical form, showing myotonia and muscle weakness, most frequently has onset in early adult life and in adolescence. The most severe form, which occurs congenitally, is associated with generalized muscular hypoplasia, mental retardation, and high neonatal mortality. Those congenitally affected offspring surviving the neonatal period invariably exhibit the classical form of the disease in late childhood or adolescence. The congenital form of DM is almost exclusively maternally transmitted. The phenomenon of anticipation (Howeler, C. J. et al., Brain, 112:779-797 (1989)), in which the disease symptoms become more severe and age at onset earlier in successive generations, is often most strikingly manifested in a family producing a congenitally affected child. To date this disease has been untreatable and its biochemical basis is not understood. Biochemical studies have failed to identify the defective protein in myotonic dystrophy, although several have implicated defects in membrane structure and function (Harper, P. S., Myotonic Dystrophy, 2nd ed., W. B. Saunders Co., London, 1989). Abnormalities in calcium transport (Seiler, D. and Kuhn, E., Schweitz Med. Wochenschr. 100:1374-1376 (1970)), membrane fluidity (Butterfield, D. A. et al., Biochemistry, 13:5078-5082 (1974)), sodiumpotassium ATPase stoichiometry (Hull, K. L., Jr. and Roses, A. D., J. Physiol., 254:169181 (1976)), and apamin receptor expression (Renaud, J. F. et al., Nature 319:676-680 (1986)) have all been reported for DM. There is also evidence of reduced phosphorylation of membrane proteins in both red blood cells (Roses, A. D. and Appel, S. H., Proc. Natl. Acad. Sci. USA 70:1855-1859 (1973)) and sarcolemmal membranes from muscle biopsies of patients (Roses, A. D. and Appel, S. H., Nature 250:245-247 (1974)). A better understanding of the underlying mechanism of DM would be very valuable in diagnosing and, ultimately, treating or preventing DM. Web site: http://www.delphion.com/details?pn=US05977333__
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Gene replacement therapy for muscular dystrophy Inventor(s): Campbell; Kevin P. (Iowa City, IA), Holt; Kathleen H. (Corlville, IA), Lim; Leland E. (Iowa City, IA), Straub; Volker (Essen, IA), Davidson; Beverly (Iowa City, IA), Williamson; Roger (Iowa City, IA), Duclos; Franck (Iowa City, IA) Assignee(s): University of Iowa Research Foundation (Iowa City, IA) Patent Number: 6,262,035 Date filed: October 1, 1998 Abstract: Disclosed is a method for treating a patient suffering from the disease sarcoglycan-deficient limb-girdle muscular dystrophy by gene replacement therapy. Sarcoglycan gene replacement therapy produces extensive long-term expression of the sarcoglycan species which restores the entire sarcoglycan complex, results in the stable association of alph.alpha.-dystroglycan with the sarcolemma, and eliminates the morphological markers of limb-girdle muscular dystrophy. In another aspect, the invention relates to a method for determining a specific defective sarcoglycan species in the tissue of a patient. The method involves culture of muscle cells obtained from the patient, and the independent introduction of expression vectors encoding each of the sarcoglycan species,.alpha.,.beta.,.gamma., and.delta., into the cultured cells with subsequent assaying for restoration of the dystrophin-glycoprotein complex. In another aspect, the invention relates to a mouse, and cells derived therefrom, homozygous for a disrupted.alpha.-sarcoglycan gene. The disruption prevents the synthesis of functional.alpha.-sarcoglycan in cells of the mouse and results in the mutant mouse having no detectable sarcospan,.beta.-,.gamma.-,.delta.-sarcoglycan, and reduced.alpha.dystroglycan in the sarcolemma of skeletal and cardiac muscles, and a reduction of dystrophin in skeletal muscle, when compared to tissue of a mouse lacking a disrupted.alpha.-sarcoglycan gene. In another aspect, the invention relates to methods for screening for therapeutic agents useful in the treatment of sarcoglycan-deficient limb-girdle muscular dystrophy. The methods involve administering a candidate therapeutic agent to a mouse, or cells derived therefrom, and assaying for therapeutic effects on the mouse or cells, with the determination of therapeutic effects being a reduction or reversal in disease progression, or a restoration of the dystroglycan complex. Excerpt(s): The term muscular dystrophy describes a group of diseases characterized by hereditary progressive muscle weakness and degeneration. Several muscular dystrophies are caused by mutations in genes that encode sarcolemmal proteins, including certain types of limb-girdle muscular dystrophy (LGMD). LGMD is genetically and clinically heterogeneous; it may be inherited in an autosomal dominant or recessive manner, and may have different rates of progression and severity. A unifying theme among the LGMDs is the initial involvement of the shoulder and pelvic girdle muscles, with relative sparing of most other muscle groups (Jackson et al., Pediatrics 41, 495-501 (1968); Bushby, K. M., Neuromusc Disord 5, 71-74 (1995)). The pace of discovery in the field of muscular dystrophy research has been rapid since the discovery of the Duchenne and Becker muscular dystrophy (DMD) gene in 1986 (Monaco et al., Nature 323, 646-650 (1986)). The DMD gene encodes dystrophin, a large cytoskeletal protein that together with other molecular components makes up the dystrophin-glycoprotein complex (DGC). The dystrophin-glycoprotein complex (DGC) is a large oligomeric complex of sarcolemmal proteins and glycoproteins in skeletal and cardiac muscle (Campbell, K. P. Cell 80, 675-679 (1995); Ozawa et al., Hum. Mol. Genet. 4, 1711-1716 (1995)). This complex consists of dystrophin, a large cytoskeletal protein which binds F-actin;.alpha.- and.beta.-dystroglycan, which bind laminin and the
Patents 281
cysteine-rich region of dystrophin, respectively;.alpha.-,.beta.-,.gamma.-, and.delta.sarcoglycan (.delta.-SG), which form a distinct subcomplex; and sarcospan, a 25 kDa protein predicted to span the membrane four times (Crosbie et al., J. Biol. Chem. 272, 31221-31224 (1997). The DGC spans the sarcolemma and is believed to play an essential role in maintaining the normal architecture of the muscle sarcolemma by constituting a link between the subsarcolemmal cytoskeleton and the extracellular matrix. This structural linkage is thought to protect muscle fibers from the mechanical stress of contraction. Mutations in different components of the DGC lead to similar dystrophic features, suggesting that the function of the DGC as a whole is dependent on intact molecular interactions between its individual subunits. The loss of one component destroys the link, and leads to muscle fiber degeneration. Several components of the DGC have been implicated in several human muscular dystrophies (Straub et al., Curr. Opin. Neurol. 10, 168-175 (1997)). Mutations in dystrophin cause Duchenne and Becker muscular dystrophy (DMD) (Hoffman et al., Cell 51, 919-928 (1987)). Two forms of congenital muscular dystrophy are caused by mutations in the extracellular matrix protein laminin 2 (Helbling-Leclerc et al., Nature Genet. 11, 216-218 (1995); Allamand et al., Hum. Mol. Genet. 6, 747-752 (1997)). Mutations in each of.alpha.-,.beta.-,.gamma.-, and.delta.-SG cause autosomal recessive LGMD types 2D, 2E, 2C, and 2F, respectively (Roberds et al., Cell 78, 625-633 (1994); Piccolo et al., Nature Genet. 10, 243-245 (1995); Lim et al., Nature Genet. 11, 257-265 (1995); Bonneman et al., Nature Genet. 11, 266-273 (1995); Noguchi et al., Science 270, 819-822 (1995); Passos-Bueno et al., Hum. Mol. Genet. 5, 815-820 (1996); Nigro et al., Hum. Mol. Genet. 5, 1179-1186 (1996); Nigro et al., Nature Genet. 14, 195-198 (1996)). Web site: http://www.delphion.com/details?pn=US06262035__ •
Measuring non-dystrophin proteins and diagnosing muscular dystrophy Inventor(s): Campbell; Kevin P. (Iowa City, IA), Ohlendieck; Kay (Iowa City, IA), Gaver; Mitchell G. (Cockeysville, MD), Ervasti; James M. (Iowa City, IA), Kahl; Steven D. (Iowa City, IA) Assignee(s): University of Iowa Research Foundation (Iowa City, IA) Patent Number: 5,413,910 Date filed: October 7, 1992 Abstract: The invention pertains to the dystrophin-glycoprotein complex of mammalian skeletal muscle and a method of isolating said complex. The components of the complex and methods of separating and isolating said components also pertain to the invention. In addition, the invention further relates to a method of diagnosing muscular dystrophy by detecting and quantifying the loss of a non-dystrophin component of the dystrophinglycoprotein complex with said loss being indicative of muscular dystrophy. Excerpt(s): Muscular dystrophy refers to a group of genetically determined myopathies characterized by progressive atrophy or degeneration of increasing numbers of individual muscle cells. The structural changes observed histologically are essentially the same in the various types of muscular dystrophies. This may, perhaps, suggest a common etiology. However, the distribution of the affected muscles is quite distinctive. This, along with the mode of inheritance, forms the basis of the classification of these diseases. The muscular dystrophies are traditionally subdivided by the patterns of initial muscle involvement, which in turn correlates fairly well with the type of genetic transmission. The three major forms of muscular dystrophy are as follows: 1) Duchenne's Muscular Dystrophy which affects most skeletal muscle groups and is
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transmitted by an X-linked recessive gene; 2) Limb Girdle Muscular Dystrophy, affecting principally the pelvic and shoulder girdle muscles and is transmitted by an autosomal recessive gene; and 3) Facioscapulohumeral Muscular Dystrophy, involves the muscles of the face and shoulder girdle and is transmitted by an autosomal dominant gene. Recently, the defective gene responsible for Duchenne's Muscular Dystrophy (DMD) has been located on the X-chromosome. The DMD gene encodes for a large molecular weight protein product, called dystrophin. This protein is localized to the sarcolemmal membrane of normal skeletal muscle, but is absent from the skeletal muscle of people with DMD, as well as dogs and mice with dystrophic muscle. A more benign form of this X-linked recessive disease is Becker's Muscular Dystrophy which is caused by an abnormal DMD gene which encodes an abnormal dystrophin protein. The exact function of dystrophin and the reasons why its absence or abnormal structure results in necrosis of dystrophic muscle fibers have not been determined. However, the amino acid sequence of dystrophin suggests that it is a membrane cytoskeletal protein. The present technology for initial detection and diagnosis of Duchenne's or Becker's Muscular Dystrophy relies on the use of an immunological probe to identify the presence of dystrophin, the absence of dystrophin, or the abnormal molecular weight or content of dystrophin in human muscle biopsies. It is not uncommon for genetic diseases to involve the loss or abnormal synthesis of more than one component or protein. In the case of muscular dystrophy, proteins other than dystrophin may be involved which are translated from genes located on different chromosomes (X chromosomes and/or autosomal chromosomes), resulting in the different forms of muscular dystrophy. The identification of other potential proteins involved in muscular dystrophy and methods of quantifying these proteins would be immensely useful to clinicians for confirming diagnosis of Duchenne's and Becker's muscular dystrophy, as well as perhaps providing an initial diagnosis of other forms of muscular dystrophy. In addition, knowledge of the function of these proteins may lead to methods of predicting prognosis of disease progression and perhaps therapeutic treatments for patients with muscular dystrophy in all of its various forms. Web site: http://www.delphion.com/details?pn=US05413910__ •
Merosin deficiency-type congenital muscular dystrophy Inventor(s): Sunada; Yoshihide (Iowa City, IA), Fardeau; Michel (Sceaux, FR), Campbell; Kevin P. (Iowa City, IA), Tome; Fernando M. S. (Paris, FR) Assignee(s): University of Iowa Research Foundation (Iowa City, IA) Patent Number: 5,863,743 Date filed: August 12, 1994 Abstract: Disclosed is a method for aiding in the diagnosis of merosin deficiency-type congenital muscular dystrophy (CMD). The method is based on the discovery of a previously unidentified form of CMD which is characterized by a substantial reduction in the levels of merosin in skeletal muscle tissue containing normal levels of dystrophin and dystrophin-associated proteins. Excerpt(s): Congenital muscular dystrophy (CMD), a very disabling muscle disease of early clinical onset, is the most frequent cause of severe neonatal hypotonia. Its manifestations are noticed at birth or in the first months of life and consist of muscle hypotonia, often associated with delayed motor milestones, severe and early contractures and joint deformities. Serum creatine kinase is raised, up to 30 times the normal values, in the early stage of the disease, and then rapidly decreases. The
Patents 283
histological changes in the muscle biopsies consist of large variation in the size of muscle fibers, a few necrotic and regenerating fibers, marked increase in endomysial collagen tissue, and no specific ultrastructural features. The diagnosis of CMD has been based on the clinical picture and the morphological changes in the muscle biopsy, but it cannot be made with certainty, as other muscle disorders may present with similar clinico-pathological features. Within the group of diseases classified as CMD, various forms have been individualized. The two more common forms are the occidental and the Japanese, the latter being associated with severe mental disturbances, and usually referred to as Fukuyama congenital muscular dystrophy (FCMD). The genetic lesion responsible for FCMD has recently been mapped to chromosome 9. It is unknown whether or not the rare cases of CMD associated with mental retardation or central nervous system abnormalities observed in occidental countries belong to the same disease entity. The determination of the gene (or genes) responsible for the various forms of CMD is required in order to clearly delineate specific members of the currently ill-defined genus. The present invention is based on the identification of a novel disease etiology which is responsible for a previously undefined member of the congenital muscular dystrophy family. The novel etiology, referred to herein as merosin deficiencytype congenital muscular dystrophy, was identified through the study of levels of specific proteins in mammalian muscle tissue. Web site: http://www.delphion.com/details?pn=US05863743__ •
Method for aiding in the diagnosis of in-frame deletion type congenital muscular dystrophy Inventor(s): Straub; Volker (Iowa City, IA), Sunada; Yoshihide (Kawaguchi, JP), Salih; Mustafa (Riyadh, SA), Allamand; Valerie (Iowa City, IA), Campbell; Kevin P. (Iowa City, IA) Assignee(s): University of Iowa Research Foundation (Iowa City, IA) Patent Number: 6,136,546 Date filed: April 9, 1998 Abstract: Disclosed are compositions and methods for aiding in the diagnosis of congenital muscular dystrophy associated with in-frame deletion in the laminin2.alpha.2 polypeptide chain in an individual. In a preferred diagnostic method embodiment, an experimental muscle tissue sample is provided from the individual and treated if necessary to render components available for antibody binding. The components of the sample are then separated on the basis of molecular weight. The separated protein components are then transferred to a solid support while maintaining the relative positions established in separation step. The transferred components are then stained with an affinity reagent which is known to bind to a C-terminal domain of the laminin-2.alpha.2 polypeptide chain. Individual afflicted with congenital muscular dystrophy associated with in-frame deletion in the laminin-2.alpha.2 polypeptide chain on the basis of positive staining in combination with reduced molecular weight of the laminin-2.alpha.2 polypeptide chain relative to the wild-type laminin-2.alpha.2 polypeptide chain. A preferred composition is a nucleic acid probe for the detection of merosin deletion-type congenital muscular dystrophy. The preferred nucleic acid probe is characterized by the ability to bind specifically to a mutant merosin nucleic acid sequence, the mutant merosin nucleic acid sequence comprising a T to C substitution at position 3973 +2 of the consensus donor splice site of exon 25.
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Excerpt(s): Laminins are a family of large extracellular glycoproteins which display a complex and still unclear repertoire of biological functions. Laminin-2, the isoform involved in congenital muscular dystrophy (CMD), is specifically expressed in the basal lamina of striated muscle and peripheral nerve. As are all members of the laminin family, it is composed of three chains: one heavy (.alpha.2) and two light chains (.beta.1 and.gamma.1) that assemble in a cross-shaped molecule with three short arms and one long arm. The C-terminal ends of each chain interact to form the triple stranded long arm of the molecule, stabilized by disulfide bonds, with a large globular (G) domain contributed to by the.alpha.2-chain. The.alpha.2-chain of laminin consists of 6 domains: I and II are part of the long arm; IIIa, IIIb and V contain cystein-rich EGF-like repeats and are predicted to have rigid rod-like structures; and IVa, IVb and VI are predicted to form globular structures. Laminin.alpha.2-chain has been shown to be a native ligand for.alpha.-dystroglycan, an extracellular component of the dystrophin-associated glycoprotein complex (DGC). This complex constitutes a link between the subsarcolemmal skeleton and the extracellular matrix. A number of components of the DGC have now been shown to be involved in muscular dystrophies suggesting a crucial role of laminin-2 and the components of the DGC in maintaining the integrity of muscle cell function. Congenital muscular dystrophy (CMD) is a clinically and genetically heterogeneous group of autosomal recessive neuromuscular disorders of early onset. In the classic form of CMD, clinical manifestations are limited to skeletal muscle with no clinical involvement of the central nervous system (CNS) although changes in the white matter have been detected by MRI. The histological changes in muscle biopsies consist of connective tissue proliferation, large variation in the size of the muscle fibers as well as some necrotic and regenerating fibers. Two groups of classical-type CMD cases can be distinguished according to the status of the.alpha.2-chain of laminin-2 (also referred to as merosin) with about half of the cases displaying a deficiency of this protein. However, even these merosin-deficient CMD cases represent a heterogeneous subgroup since some patients display a total deficiency of the.alpha.2-chain of laminin-2 whereas this protein is expressed in others, though at a reduced level. Linkage analyses and homozygosity mapping studies have led to the localization of the CMD locus to chromosome 6q2 (Hillaire et al., Hum. Mol. Genet. 3: 1657-1661 (1994); and HelblingLeclerc et al., C. R. Acad. Sci. Paris 318: 1245-1252 (1995)), in the region containing the gene encoding the.alpha.2-chain of laminin (LAMA-2) (Vuolteenaho et al., J. Cell Biol. 124: 381-394 (1994)). Recently, mutations affecting this gene have been identified in CMD patients (Helbling-Leclerc et al., Nat. Genet. 11: 216-218 (1995); and Nissinen et al., Am. J. Hum. Genet. 58: 1177-1184 (1996). Web site: http://www.delphion.com/details?pn=US06136546__ •
Method for assaying a human muscular dystrophy protein Inventor(s): Ishiguro; Tsuneo (Kawasaki, JP), Eguchi; Chikahiko (Kawasaki, JP) Assignee(s): Ajinomoto Co., Inc. (Tokyo, JP) Patent Number: 5,340,718 Date filed: January 27, 1993 Abstract: Methods and polypeptides for assaying human proteins associated with Duchenne muscular dystrophy, are disclosed. Excerpt(s): The present invention relates to a method for assaying dystrophin which is a protein defective in a human suffering from Duchenne muscular dystrophy (DMD) which is a hereditary disease. Duchenne muscular dystrophy is a hereditary disease
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which is developed almost only in males. A gene which is defective peculiarly to this disease is located on the X chromosome and its sequence has been elucidated [M. Konig, E. P. Hoffman, C. J. Bertelson, A. P. Monaco, C. Feenet and L. M. Kunkel: Cell, 50, 509 (1987), E. P. Hoffman, A. P. Monaco, C. C. Feeher and L. M. Kunkel, Science, 238, 347 (1987)]. If any antibody capable of specifically recognizing dystrophin which is a protein encoded by this gene is produced, a deletion or defect of dystrophin specific to this disease could be detected and such would be useful. A related method was tried by Hoffman et al., using the gene from mice suffering from a disease which is the same type as Duchenne muscular dystrophy [E. P. Hoffman, R. H. Brown, Jr. and L. M. Kunkel, Cell, 51, 919 (1987); E. P. Hoffman, C. M. Knudson, K. P. Campbell and L. M. Kunkel, Nature, 330, 754 (1987)]. However, the method of Hoffman et al. uses a gene from mice, the amino acid sequence of which is different by about 10% from that of humans, to produce the antibody so that it is inappropriate to determine dystrophin possessed by humans. Moreover, according to this method, protein having a high molecular weight such as 208 amino acid residues or 410 amino acid residues is used as an antigen and hence, the method has a shortcoming that an antibody capable of reacting not only with dystrophin but also with many other proteins is formed and that the antibody fails to specifically react with dystrophin alone. In order to compensate for the poor specificity of reaction, Hoffman et al. adopted a method using a specimen obtained by previously homogenizing cells to be tested followed by separating protein from the homogenate by electrophoresis, and then performing an antigen-antibody reaction with respect to the specimen. For this reason, the method encounters a drawback that operations are complicated and is thus unsatisfactory. In general, conventional methods for assaying dystrophin have drawbacks in that antibodies capable of specifically reacting only with dystrophin could not be obtained since a gene from a mouse, which is different from that of a human, has been used for preparation of the antibody. Further, operations are complicated since the method comprises using a specimen obtained by previously homogenizing cells to be tested and separating protein from the homogenate by electrophoresis and performing an antigen-antibody reaction with respect to the specimen. Therefore, the present inventors have made extensive investigations to discover a method for assaying the protein in cells in a simple manner, by preparing an antiserum capable of specifically reacting only with dystrophin or an antibody fraction separated from the antiserum using a part of dystrophin encoded by human Duchenne muscular dystrophy-associated gene and performing an antigenantibody reaction between a substance to be tested and the antiserum or antibody fraction. Web site: http://www.delphion.com/details?pn=US05340718__ •
Method of in vitro preconditioning healthy donor's myoblasts before transplantation thereof in compatible patients suffering of recessive myopathies like muscular dystrophy, for improving transplantation success Inventor(s): Tremblay; Jacques P. (Bernieres, CA) Assignee(s): Universite Laval (Quebec, CA) Patent Number: 5,833,978 Date filed: March 16, 1995 Abstract: A method of pretreating healthy donor's myoblast cultures with growth or trophic factors like basic fibroblast growth factor (bFGF) on transplantation to subjects suffering of recessive myopathy like muscular dystrophy is disclosed and claimed.
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Recipient muscles show a higher percentage of functional cells, demonstrated by the higher incidence of dystrophin-positive fibers, and does not require previous preconditioning of recipient muscles by irradiation or toxin administration. Donor mouse myoblasts expressing the reporter gene.beta.- galactosidase were grown with 100 ng/ml bFGF during the last two days before injecting them in the left tibialis anterior (TA) muscles of recipient MHC-compatible mdx mice, an experimental animal model of muscular dystrophy. Myoblasts from the same primary cultures were also grown without bFGF and injected in the right TA muscles as control. The recipient mice were immunosuppressed with FK 506. Twenty-eight days after myoblast transplantation, the percentage of.beta.- galactosidase-positive fibers was significantly higher (more than a 4 fold increase) following culture with bFGF than without bFGF. Almost all.beta.galactosidase-positive-fibers were also dystrophin positive. Excerpt(s): The present invention is a method for preconditioning healthy donor's myoblasts in vitro before transplantation thereof in compatible patients suffering of recessive myopathies, particularly of muscular dystrophy. This in vitro preconditioning improves the success of the transplantation while not requiring an in vivo preconditioning of the patient's muscle by irradiation or by administering muscular toxin. Duchenne muscular dystrophy (DMD) is a progressive disease characterized by the lack of dystrophin under the sarcolemmal membrane.sup.6,19,28,37. One possible way to introduce dystrophin in the muscle fibers of the patients to limit the degeneration is to transplant myoblasts obtained from normal subjects.sup.30,34,35. Several groups have tried myoblast transplantations to DMD patients but poor graft success was observed.sup.17,22,24,38. Even in experimental myoblast transplantation using mdx mice, an animal model of DMD.sup.10,25,29, large amount of dystrophinpositive fibers were observed only when nude mdx mice were previously irradiated to prevent regeneration of the muscle fibers by host myoblasts.sup.32,43. High percentage of dystrophin-positive fibers was also observed in mdx mice immunosuppressed with FK 506 and in SCID mice, in both cases muscles were previously damaged by notexin injection and irradiated.sup.23,27. These results indicate that to obtain successful myoblast transplantation, it is necessary to have not only an immunodeficient mouse or a mouse adequately immunosuppressed but also a host muscle which has been adequately preconditioned. It is, however, impossible in clinical studies to use damaging treatments such as marcaine, notexin and irradiation. If good myoblast transplantation results can be obtained without using such techniques, this would be very helpful for myoblast transplantation in humans. Recently there has been an increasing interest on the effects of basic fibroblast growth factor (bFGF) and other growth factors on myoblast cultures and myoblast cell lines.sup.1,4,5. Basic FGF has been reported to both stimulate proliferation and inhibit differentiation of skeletal myoblasts in vitro.sup.15,16. Other growth or trophic factors like insulin growth factor I, transferrin, platelet-derived growth factor, epidermal growth factor, adrenocorticotrophin and macrophage colony-stimulating factor as well as C kinase proteins activators or agonists by which the effect of bFGF is mediated.sup.20 may also have similar or even better effects than bFGF on the success of myoblast transplantation. The use of these stimulating properties to enhance the success of transplantation by in vitro preconditioning of donor's cells and to replace at least partially the use of previously known methods of in vivo preconditioning of recipients' cells has never been suggested before. Web site: http://www.delphion.com/details?pn=US05833978__
Patents 287
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Method of treatment for muscular dystrophy Inventor(s): Antoku; Yasunobu (Kurume, JP), Sakai; Tetsuo (Yame, JP), Tsukamoto; Kosuke (Kurume, JP), Koike; Fumihiko (Saga, JP), Tanaka; Kaoru (Fukuoka, JP) Assignee(s): MinoPhagen Pharmaceutical Company (Tokyo, JP) Patent Number: 5,434,142 Date filed: August 24, 1993 Abstract: Administering to a patient of muscular dystrophy a pharmaceutical agent containing glycyrrhizin and/or a pharmaceutically acceptable salt thereof as effective components is effective against muscular dystrophy, particularly, Duchenne or Becker muscular dystrophy and is highly safe with less side effect. Excerpt(s): This invention relates to a method of treatment for muscular dystrophy and, more particularly, to a method of treatment for muscular dystrophy such as Duchenne muscular dystrophy, Becker muscular dystrophy and the like. The Duchenne muscular dystrophy is a sex-linked recessive disease occuring in childhood, in which muscle weakness and muscular wasting in the proximal parts of extremities and trunk are progressed, resulting in a death at about twenty. The Becker muscular dystrophy is also a sex-linked recessive disease showing the same symptoms, although its onset age is older and tile progression is slower, compared with the Duchenne type. Other muscular dystrophies include limb-girdle muscular dystrophy, facioscapulohumeral (FSH) muscular dystrophy, congenital muscular dystrophy, and the like. Web site: http://www.delphion.com/details?pn=US05434142__
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Muscular dystrophy protein, dystrophin Inventor(s): Kunkel; Louis M. (Hyde Park, MA), Koenig; Michel (Boston, MA), Hoffman; Eric P. (Newton, MA), Monaco; Anthony (Boston, MA) Assignee(s): The Children's Medical Center Corporation (Boston, MA) Patent Number: 5,239,060 Date filed: December 22, 1987 Abstract: The invention relates to a muscular dystrophy (MD) probe comprising a substantially purified single-stranded nucleic acid sequence capable of hybridizing to a region of DNA on a human X chromosome between the deletion break point at Xp21.3 and the translocation break point at X;11. The invention also relates to a 14 kb cDNA corresponding to the complete MD gene and probes produced therefrom useful in genetic methods of diagnosis of MD. Furthermore, the invention relates to the polypeptide, dystrophin, which corresponds to the MD gene product, and antibodies thereto that are useful in a variety of methods for immunodiagnosis of MD. Excerpt(s): This invention relates to the detection and treatment of hereditary disease, and in particular to the detection and diagnosis of Duchenne, Becker and Outlier muscular dystrophies (MD) by various methods. Duchenne muscular dystrophy (DMD) is an X-linked recessive genetic disorder which affects about 1 in 3,300 males. Traits associated with DMD (DMD phenotype) are well known and may include elevated creatine phosphokinase levels in serum (at least 10.times. the normal level), delayed development of motor function, and muscle weakness characterized by the replacement of muscle fiber with adipose and fibrose tissue accompanied by a marked variation in muscle size. Until recently, carrier identification in DMD families generally was
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accomplished by detecting elevated levels of creatine phosphokinase in serum. Becker muscular dystrophy (BMD) is also an X-linked recessive genetic disorder, but occurs at only 10% of the frequency of DMD. BMD is a more benign form of muscular dystrophy which follows a less rapid clinical course than DMD. Both DMD and BMD are caused by mutations in the DMD gene located in the Xp21 region of the short arm of the human X chromosome. Web site: http://www.delphion.com/details?pn=US05239060__ •
Probes for and nucleic acid encoding the muscular dystrophy protein, dystrophin Inventor(s): Kunkel; Louis M. (Hyde Park, MA), Hoffman; Eric P. (Newton, MA), Monaco; Anthony (Boston, MA), Koenig; Michel (Boston, MA) Assignee(s): The Children's Medical Center Corporation (Boston, MA) Patent Number: 5,621,091 Date filed: March 17, 1995 Abstract: The invention relates to a muscular dystrophy (MD) probe comprising a substantially purified single-stranded nucleic acid sequence capable of hybridizing to a region of DNA on a human X chromosome between the deletion break point at Xp21.3 and the translocation break point at X;11. The invention also relates to a 14 kb cDNA corresponding to the complete MD gene and probes produced therefrom useful in genetic methods of diagnosis of MD. Furthermore, the invention relates to the polypeptide, dystrophin, which corresponds to the MD gene product, and antibodies thereto that are useful in a variety of methods for immunodiagnosis of MD. Excerpt(s): This invention relates to the detection and treatment of hereditary disease, and in particular to the detection and diagnosis of Duchenne, Becker and Outlier muscular dystrophies (MD) by various methods. Duchenne muscular dystrophy (DMD) is an X-linked recessive genetic disorder which affects about 1 in 3,300 males. Traits associated with DMD (DMD phenotype) are well known and may include elevated creatine phosphokinase levels in serum (at least 10.times. the normal level), delayed development of motor function, and muscle weakness characterized by the replacement of muscle fiber with adipose and fibrose tissue accompanied by a marked variation in muscle size. Until recently, carrier identification in DMD families generally was accomplished by detecting elevated levels of creatine phosphokinase in serum. Becker muscular dystrophy (BMD) is also an X-linked recessive genetic disorder, but occurs at only 10% of the frequency of DMD. BMD is a more benign form of muscular dystrophy which follows a less rapid clinical course than DMD. Both DMD and BMD are caused by mutations in the DMD gene located in the Xp21 region of the short arm of the human X chromosome. Web site: http://www.delphion.com/details?pn=US05621091__
Patents 289
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Remedy for myotonic dystrophy Inventor(s): Ohsawa; Nakaaki (Osaka, JP), Sugino; Masakazu (Osaka, JP), Endo; Tomio (Nishinomiya, JP) Assignee(s): Kanebo Ltd. (Tokyo, JP) Patent Number: 5,834,451 Date filed: April 15, 1997 Abstract: A remedy for myotonic dystrophy, containing dehydroepiandrosterone sulfate or a pharmacologically acceptable salt thereof, being efficacious for myotonia, adynamia and amyotrophy, and having a high safety. Excerpt(s): This application is a 371 of PCT/JP95/01561 filed Aug. 7, 1995. The present invention relates to a remedy efficacious for symptomatic improvement in myotonic dystrophy and various other diseases manifesting myotonia. Myotonic dystrophy (hereinafter referred to sometimes as MyD) is an autosomal-dominant hereditary disease caused by abnormalities of the long arm of chromosome 19 and its morbidity is said to be 4 to 5 in 100,000. MyD is a degenerative disease, the cardinal symptoms of which are muscular atrophy and decreased muscle strength dominantly found in muscles of the face and neck and in distal muscles of the limbs, and appearance of repetitive muscle cell membrane action potentials in skeletal muscles on contraction and consequent delays in relaxation (myotonia), and which is complicated by multiple organ disorders. Web site: http://www.delphion.com/details?pn=US05834451__
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Use of isopropylaminopyrimidine in the chemotherapy of muscular dystrophy, myopathy and mytonia Inventor(s): Huve; Pierre M. (Paris, FR) Assignee(s): Societe d'Etudes de Produits Chimiques (FR) Patent Number: 4,344,947 Date filed: October 29, 1980 Abstract: A method for the chemotherapy of muscular dystrophy which includes administrating an effective amount of 2 isopropylaminopyrimidine. Excerpt(s): The present invention is directed to a new use of an existing compound. U.S. Pat. No. 4,073,895 relates to the use of a substituted salt of 2 aminopyrimidine. This patent in fact teaches that a particular salt of 2 aminopyrimidine, namely 2 isopropylaminopyrimidine orthophosphate (IAPP), is useful as an active agent for the treatment of neuropathies. Although this use is known, the particular efficacy of the salt against muscular dystrophy has yielded unexpected and superior results. The invention broadly comprises a method for the chemotherapy of muscular dystrophy, which comprises administering an effective dosage of 2 isopropylaminopyrimidine or therapeutically acceptable salts of the same or the hydroxylated and oxygenated metabolites thereof. In the following discussion, the specific compound used for testing is 2 isopropylaminopyrimidine orthophosphate as disclosed in U.S. Pat. No. 4,073,895, which patent is hereby incorporated by reference in its entirety in this application. Web site: http://www.delphion.com/details?pn=US04344947__
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Patent Applications on Muscular Dystrophy 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 muscular dystrophy: •
13245, a novel human myotonic dystrophy type protein kinase and uses therefor Inventor(s): Kapeller-Libermann, Rosana; (Chestnut Hill, MA) Correspondence: AKIN, GUMP, STRAUSS, HAUER & FELD, L.L.P. ONE COMMERCE SQUARE; 2005 MARKET STREET, SUITE 2200; PHILADELPHIA; PA; 19103; US Patent Application Number: 20020160483 Date filed: October 23, 2001 Abstract: The invention provides isolated nucleic acids molecules, designated 13245 nucleic acid molecules, which encode a novel myotonic dystrophy type protein kinase. The invention also provides antisense nucleic acid molecules, recombinant expression vectors containing 13245 nucleic acid molecules, host cells into which the expression vectors have been introduced, and non-human transgenic animals in which a 13245 gene has been introduced or disrupted. The invention still further provides isolated 13245 proteins, fusion proteins, antigenic peptides and anti-13245 antibodies. Diagnostic methods utilizing compositions of the invention are also provided. Excerpt(s): This application is entitled to priority pursuant to 35 U.S.C.sctn.119(e) to U.S. provisional patent application 60/242,429 which was filed on Oct. 23, 2000. Protein phosphorylation, for example at serine, threonine, and tyrosine residues, is a key regulatory mechanism for a variety of cellular processes. Protein phosphorylation is influenced primarily by enzymes of two types, namely protein kinases (PKs) and protein phosphatases (PPs). PKs catalyze addition of a phosphate moiety to a protein amino acid residue (generally a serine, threonine, or tyrosine residue), and PPs catalyze removal of such moieties. The catalytic activities of PKs and PPs are, in turn, influenced by the state of the cell and the environment in which it finds itself. Myotonic dystrophy type PKs (MDPKs) are associated with modulation of cell morphology, shape, and contractility. MDPKs are also known to modulate the activity of skeletal muscle voltagegated sodium channels, but not cardiac muscle voltage-gated sodium channels. MDPKs thus have a role in a variety of musculodegenerative and other musculoskeletal disorders including, for example, muscular dystrophy (MD) of various types (e.g., Duchenne's MD, limb-girdle MD, Becker MD, facioscapulohumerol MD, mitochondrial myopathy, and congenital myopathy) and myotonic dystrophies (e.g., Steinert's disease and Thomsen's disease). Web site: http://appft1.uspto.gov/netahtml/PTO/search-bool.html
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This has been a common practice outside the United States prior to December 2000.
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Diagnostics, assay methods and amelioration of muscular dystrophy symptoms Inventor(s): Kaufman, Stephen J. (Urbana, IL) Correspondence: GREENLEE WINNER AND SULLIVAN P C; 5370 MANHATTAN CIRCLE; SUITE 201; BOULDER; CO; 80303; US Patent Application Number: 20020192710 Date filed: February 20, 2002 Abstract: The present disclosure provides compositions and sequences for the diagnosis, genetic therapy of certain muscular dystrophies, especially muscular dystrophy resulting from a deficiency in dystrophin protein or a combined deficiency in dystrophin and utrophin, and methods and compositions for the identification of compounds which increase expression of the.alpha.7 integrin. Expression of the integrin.alpha.BX2 polypeptide in muscle cells results in better physical condition in a patient or an animal lacking normal levels of dystrophin or dystrophin and utrophin. The present disclosure further provides immunological and nucleic acid based methods for the diagnosis of scapuloperoneal muscular dystrophy, where there is a reduction in or absence of.alpha.7A integrin expression in muscle tissue samples and normal levels of laminin-{fraction (2/4)} in those same samples. The present disclosure further provides methods for identifying compositions which increase the expression of.alpha.7 integrin protein in muscle cells of dystrophy patients. Excerpt(s): This application claims priority from U.S. Provisional Application 60/270,645 filed Feb. 20, 2001 and from U.S. Provisional Application 60/286,890 filed Apr. 27, 2001, both of which are incorporated herein. The field of the present invention is the area of medical treatment and diagnosis using molecular technology. In particular, the present invention utilizes gene therapy and drug induced gene expression to ameliorate the physical condition of muscular dystrophy patients, especially those lacking dystrophin or lacking dystrophin and utrophin or those with lower than normal levels of.alpha.7 integrin, and in another aspect, this invention relates to the use of nucleic acid probes or primers or immunological probes for detecting the reduction of or lack of expression of the.alpha.7.beta.1 integrin in scapuloperoneal muscular dystrophy (SPMD) as well as to the use of assays to identify compounds which induce increased expression via.alpha.7.beta.1 integrin transcriptional regulatory sequences. Scapuloperoneal (SP) muscular dystrophy is one of a heterogenous group of scapuloperoneal syndromes affecting the muscles of the shoulder girdle and peroneal. SP syndromes were formerly grouped as one genetic disease, but clinical analysis and genetic mapping have revealed that this syndrome includes at least two distinct diseases with different underlying genetic defects. SPMD is an autosomal dominant disorder characterized by myopathy and progressive muscle weakening in the shoulder girdle and peroneal muscles. The disease has late onset, with affected individuals first displaying symptoms in their late teens or early twenties and up to the late fifties. This disease affects the legs and feet (with foot drop and hammer toes) and the proximal and/or distal arms. Patients have scapular winging and asymmetry. There is intolerance to exercise. Other symptoms include contractures, hearing loss, twitching, muscle cramps, facial weakness and cardiac disorders. Death results from cardiac or respiratory failure. Although the underlying genetic defect has not been identified previously, SPMD has been mapped by genetic linkage analysis to human chromosome 12q13.3-q15. Web site: http://appft1.uspto.gov/netahtml/PTO/search-bool.html
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GA binding protein and neurite derived growth factors for use in the treatment of muscular dystrophy Inventor(s): Khurana, Tejvir S. (Pennsylvania, PA) Correspondence: BIRCH STEWART KOLASCH & BIRCH; PO BOX 747; FALLS CHURCH; VA; 22040-0747; US Patent Application Number: 20020086017 Date filed: May 10, 2001 Abstract: The present invention relates to methods and compositions for the treatment of muscular dystrophia, and in particular Duchenne's muscular dystrophy. More specifically the invention relates to GA Binding Protein, in particular GABP.alpha. and/or GABP.beta., or neurite derived growth factors, in particular heregulin polypeptides, useful for the treatment of muscular dystrophy, in particular Duchenne's muscular dystrophy. Excerpt(s): This application is a Continuation of PCT International Application No. PCT/DK99/00694 filed on Dec. 9, 1999, which was published in English and which designated the United States and on which priority is claimed under 35 U.S.C.sctn.120, the entire contents of which are hereby incorporated by reference. The present invention relates to methods and compositions for the treatment of muscular dystrophia, and in particular Duchenne's muscular dystrophy. More specifically the Invention relates to GA Binding Protein, In particular GABP.alpha. and/or GABP.beta., and neurite derived growth factors, in particular heregulin polypeptides, useful for the treatment of muscular dystrophy, in particular Duchenne's muscular dystrophy. Neurite derived growth factors are members of the neuregulin family of polypeptide growth factor homologues that includes heregulin, NDF, ARIA and GGF [Fischbach G D & Rosen K M: ARIA--A neuromuscular junction neuregulin; Annu. Rev. Neurosci. 1997 20 429-458]. These ligands and their receptors have wide ranging effects that are considered critical for nervous system development [Meyer D & Birchmeier C: Multiple essential functions of neuregulin in development; Nature 1995 378 386-3; Lemke G: Neuregulins in Development; Mol. Cell. Neurosci. 1996 7 247-262; Fischbach & Rosen, op cit.]. Web site: http://appft1.uspto.gov/netahtml/PTO/search-bool.html
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Intron associated with myotonic dystrophy type 2 and methods of use Inventor(s): Ranum, Laura P.W. (St. Paul, MN), Liquori, Christina; (Minneapolis, MN), Day, John W. (Minneapolis, MN) Correspondence: MUETING, RAASCH & GEBHARDT, P.A. P.O. BOX 581415; MINNEAPOLIS; MN; 55458; US Patent Application Number: 20030108887 Date filed: May 10, 2002 Abstract: The present invention provides methods for identifying individuals not at risk for developing myotonic dystrophy type 2 (DM2), and individuals that have or at risk for developing DM2. The present invention also provides isolated polynucleotides that include a repeat tract within intron 1 of the zinc finger protein 9. Excerpt(s): This application claims the benefit of U.S. Provisional Application Serial No. 60/290,365, filed May 11, 2001, U.S. Provisional Application Serial No. 60/302,022, filed Jun. 29, 2001, and U.S. Provisional Application Serial No. 60/337,831, filed Nov. 13,
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2001, which are incorporated by reference herein. DM is a dominantly-inherited, multisystemic disease with a consistent constellation of seemingly unrelated and rare clinical features including: myotonia, muscular dystrophy, cardiac conduction defects, posterior iridescent cataracts, and endocrine disorders (Harper, Myotonic Dystrophy, W. B. Saunders, London, ed. 2, 1989)). DM was first described nearly 100 years ago, but the existence of more than one genetic cause was only recognized after genetic testing became available for myotonic dystrophy type 1 (DM1) (Thornton et al., Ann. Neurology, 35, 269 (1994), Ricker et al., Neurology, 44, 1448 (1994)). DM1 is caused by an expanded CTG repeat on chromosome 19 that is both in the 3' untranslated region of the dystrophia myotonica-protein kinase (DMPK) gene, and in the promoter region of the immediately adjacent homeodomain gene SIX5 (Groenen and Wieringa, Bioessays, 20, 901 (1998), Tapscott, Science, 289, 1701 (2000)). How the CTG expansion in a noncoding region of a gene causes the complex DM phenotype remains unclear. Suggested mechanisms include: (i) haploinsufficiency of the DMPK protein; (ii) altered expression of neighboring genes, including SIX5; and (iii) pathogenic effects of the CUG expansion in RNA which accumulates as nuclear foci and disrupts cellular function. Several mouse models have developed different aspects of DM1: a model expressing mRNA with CUG repeats manifests myotonia and the myopathic features of DM1; a DMPK knockout has cardiac abnormalities; and SIX5 knockouts have cataracts. Taken together, these data have been interpreted to suggest that each theory may contribute to DM1 pathogenesis and that DM1 may be a regional gene disorder. Web site: http://appft1.uspto.gov/netahtml/PTO/search-bool.html •
Method of early detection of duchenne muscular dystrophy and other neuromuscular disease Inventor(s): Hampton, Thomas G. (Framingham, MA) Correspondence: LAHIVE & COCKFIELD; 28 STATE STREET; BOSTON; MA; 02109; US Patent Application Number: 20030003052 Date filed: June 19, 2002 Abstract: The mdx mouse is a model of Duchenne muscular dystrophy. The present invention describes that mdx mice exhibited clinically relevant cardiac phenotypes. A non-invasive method of recording electrocardiograms (ECGs) was used to a study mdx mice (n=15) and control mice (n=15). The mdx mice had significant tachycardia, consistent with observations in patients with muscular dystrophy. Heart-rate was nearly 15% faster in mdx mice than control mice (P<0.01). ECGs revealed significant shortening of the rate-corrected QT interval duration (QTc) in mdx mice compared to control mice (P<0.05). PR interval duration were shorter at baseline in mdx compared to control mice (P<0.05). The muscarinic antagonist atropine significantly increased heart-rate and decreased PR interval duration in C57 mice. Paradoxically, atropine significantly decreased heart-rate and increased PR interval duration in all mdx mice. Pharmacological autonomic blockade and baroreflex sensitivity testing demonstrated an imbalance in autonomic nervous system modulation of heart-rate, with decreased parasympathetic activity and increased sympathetic activity in mdx mice. These electrocardiographic findings in dystrophin-deficient mice provide new bases for diagnosing, understanding, and treating patients with Duchenne muscular dystrophy. Excerpt(s): This application claims priority to U.S. provisional patent application serial No. 60/299,302, filed Jun. 19, 2001, and to U.S. provisional patent application serial No.
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60/338,821, filed Nov. 17, 2001. The contents of these provisional patent applications are incorporated herein by reference in their entirety. Dysfunction of the autonomic nervous system is an under-recognized but important aspect of the etiological and clinical manifestation of neuromuscular disorder such as Duchenne muscular dystrophy (DMD). DMD is an X-linked inherited disorder that affects over nearly 30 out of every 100,000 boys born in the United States. The disorder results from a defect in the gene for an enormous protein called dystrophin, which forms part of the scaffold in muscle fibers. Although the disorder is present from the initial stages of fetal development, there is no physical indication at birth that the baby is abnormal. Rarely is there physical diagnosis in the first year of life. Problems are usually not evident until 18 months to 4 years of age. Usually diagnosis is not made until the child is five. Nearly 50% of affected boys do not walk until 18 months of age or later. Duchenne children have difficulty climbing and getting up from the floor. Parents often comment that their child falls frequently. By the age 3 to 5 years, generalized muscle weakness becomes more obvious. Parents may be falsely encouraged by a seeming improvement at school age, but this may be due to natural growth and development. Weakness progresses rapidly after age 8 or 9, resulting in the inability to walk or stand unassisted. Leg braces may make walking possible for a year or two, but by early adolescence walking becomes impossible. There are some boys with Duchenne muscular dystrophy who have problems with delay in mental or language development. Eventually all the major muscles are affected. Lung capacity may decrease, resulting in an increased susceptibility to respiratory infections. Cardiac and respiratory failure are common in Duchenne patients. Autonomic nervous system abnormalities have now been frequently reported in patients. The cardiac phenotype includes decreased parasympathetic nervous activity and increased sympathetic nervous activity. Currently there is no reliable mode of prenatal diagnosis or cure. For a series of reasons, diagnosis of Duchenne patients using DNA markers from amniocytes is error ridden and deletion mutants are detectable in only 65% of cases. Therefore, early detection of the disease before locomotor or autonomic disturbances reduce quality of life or irreversibly affect outcome of the disease could significantly improve life-quality prospects and longevity in those afflicted with dystrophin-deficiency related diseases. Web site: http://appft1.uspto.gov/netahtml/PTO/search-bool.html •
Method of in vitro preconditioning healthy donor's myoblasts before transplantation thereof in compatible patients suffering of myopathies like muscular dystrophy, for improving transplantation success Inventor(s): Tremblay, Jacques P. (Berniere, CA) Correspondence: BIRCH STEWART KOLASCH & BIRCH; PO BOX 747; FALLS CHURCH; VA; 22040-0747; US Patent Application Number: 20020182193 Date filed: March 21, 2002 Abstract: A method of pretreating healthy donor's myoblast cultures with growth or trophic factors like basic fibroblast growth factor (bFGF) and with concanavalin A on transplantation to subjects suffering of myopathy like muscular dystrophy is disclosed and claimed. Recipient muscles show a higher percentage of functional cells, a four-fold increase, demonstrated by the higher incidence of dystrophin-positive fibers, and does not require previous preconditioning of recipient muscles by irradiation or toxin administration. The recipient subjects were immunosuppressed with FK 506. When
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growing myoblasts with 20.mu.g/ml concanavalin A or 100 ng/ml TPA for two to four days, migration of donor cells in recipient tissue was increased by 3-4 fold.This suggests that, when using primary cultures, metalloproteases are secreted by fibroblasts, resulting in a greater degradation of the extracellular matrix. Both metalloproteases and bFGF appear beneficial for the success of the transplantation. The use of recombinant myoblast expressing metalloproteases is also contemplated. Excerpt(s): The present invention is a method for preconditioning healthy donor's myoblasts in vitro before transplantation thereof in compatible patients suffering of recessive myopathies, particularly of muscular dystrophy. This in vitro preconditioning improves the success of the transplantation while not requiring an in vivo preconditioning of the patient's muscle by irradiation or by administering muscular toxin. Duchenne muscular dystrophy (DMD) is a progressive disease characterized by the lack of dystrophin under the sarcolemmal membrane.sup.6,19,28,37. One possible way to introduce dystrophin in the muscle fibers of the patients to limit the degeneration is to transplant myoblasts obtained from normal subjects.sup.30,34,35. Several groups have tried myoblast transplantations to DMD patients but poor graft success was observed.sup.17,22,24,38. Even in experimental myoblast transplantation using mdx mice, an animal model of DMD.sup.10,25,29, large amount of dystrophinpositive fibers were observed only when nude mdx mice were previously irradiated to prevent regeneration of the muscle fibers by host myoblasts.sup.32,43. High percentage of dystrophin-positive fibers was also observed in mdx mice immunosuppressed with FK 506 and in SCID mice, in both cases muscles were previously damaged by notexin injection and irradiated.sup.23,27. These results indicate that to obtain successful myoblast transplantation, it is necessary to have not only an immunodeficient mouse or a mouse adequately immunosuppressed but also a host muscle which has been adequately preconditioned. It is, however, impossible in clinical studies to use damaging treatments such as marcaine, notexin and irradiation. If good myoblast transplantation results can be obtained without using such techniques, this would be very helpful for myoblast transplantation in humans. Recently there has been an increasing interest on the effects of basic fibroblast growth factor (bFGF) and other growth factors on myoblast cultures and myoblast cell lines.sup.1,4,5. Basic FGF has been reported to both stimulate proliferation and inhibit differentiation of skeletal myoblasts in vitro.sup.15,16. Other growth or trophic factors like insulin growth factor I, transferrin, platelet-derived growth factor, epidermal growth factor, adrenocorticotrophin and macrophage colony-stimulating factor as well as C kinase proteins activators or agonists by which the effect of bFGF is mediated.sup.20 may also have similar or even better effects than bFGF on the success of myoblast transplantation.sup.7. The use of these stimulating properties to enhance the success of transplantation by in vitro preconditioning of donor's cells and to replace at least partially the use of previously known methods of in vivo preconditioning of recipients' cells has never been suggested before. Web site: http://appft1.uspto.gov/netahtml/PTO/search-bool.html
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Methods for treating muscular dystrophy Inventor(s): Mulligan, Richard C. (Lincoln, MA), Kunkel, Louis M. (Westwood, MA), Gussoni, Emanuela; (Winchester, MA), Soneoka, Yuko; (Washington, DC) Correspondence: HAMILTON, BROOK, SMITH & REYNOLDS, P.C. 530 VIRGINIA ROAD; P.O. BOX 9133; CONCORD; MA; 01742-9133; US Patent Application Number: 20020182192 Date filed: March 14, 2002 Abstract: Methods for treating muscle diseases via bone marrow transplantation of either allogeneic cells or autologous cells engineered to express dystrophin or other gene products affected in muscle diseases are disclosed. Bone marrow cells and bone marrow SP cells (a highly purified population of hematopoietic stem cells) can be used in the methods. Muscle diseases include muscular dystrophies, such as Duchenne muscular dystrophy, Becker muscular dystrophy and limb-girdle muscular dystrophies. Excerpt(s): This application is a continuation of International Application No. PCT/US00/25128, filed Sep. 14, 2000, which claims the benefit of U.S. Provisional Application No. 60/153,821, filed Sep. 14, 1999. The teachings of the above applications are incorporated herein by reference in their entirety. There are probably about 3,000 muscle proteins, each encoded by a different gene. Some muscle proteins are part of the structure of muscle fibers, while others influence chemical reactions in the fibers. A defect in a muscle protein gene can lead to a muscle disease. The precise defect in a muscle protein gene can influence the nature and severity of a muscle disease. Muscular dystrophies are caused by defects in muscle protein genes and are typically progressive disorders mainly of striated muscle that lead to breakdown of muscle integrity, often resulting in death. The histologic picture shows variation in fiber size, muscle cell necrosis and regeneration, and often proliferation of connective and adipose tissue. The precise defect in a muscle protein gene determines the nature and severity of a muscular dystrophy. For example, two major types of muscular dystrophy, Duchenne muscular dystrophy (DMD) and Becker muscular dystrophy (BMD), are allelic, lethal degenerative muscle diseases. DMD results from mutations in the dystrophin gene on the X-chromosome (Hoffinan et al., N. Engl. J. Med., 318:1363-1368 (1988)), which usually result in the absence of dystrophin, a cytoskeletal protein in skeletal and cardiac muscle. BMD is the result of mutations in the same gene (Hoffinan et al., N. Engl. J. Med., 318:1363-1368 (1988)), but dystrophin is usually expressed in muscle but at a reduced level and/or as a shorter, internally deleted form, resulting in a milder phenotype. Web site: http://appft1.uspto.gov/netahtml/PTO/search-bool.html
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Pharmaceutical composition for treatment of Duchenne muscular dystrophy Inventor(s): Matsuo, Masafumi; (Kobe-shi, JP), Kamei, Shoichiro; (Kobe-shi, JP) Correspondence: GREENBLUM & BERNSTEIN, P.L.C. 1941 ROLAND CLARKE PLACE; RESTON; VA; 20191; US Patent Application Number: 20020055481 Date filed: August 16, 2001 Abstract: The invention provides an isolated and purified DNA set forth as SEQ ID NO:15 in the Sequence Listing and an antisense oligonucleotide complementary to the
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DNA. The DNA represents the splicing enhancer sequence (SES) in exon 45 of human dystrophin gene, and serves as a template in preparation of the antisense oligonucleotide, which is used to induce exon 45 skipping in certain group of patient with Duchenne muscular dystrophy to restore the reading frame of dystrophin mRNA. Excerpt(s): The present invention relates to pharmaceutical compositions for treatment of Duchenne muscular dystrophy, which pharmaceutical compositions are designed to correct an existing shift of the amino acid reading frame in dystrophin pre-mRNA, by inducing in a predetermined manner an exon skipping in the pre-mRNA having the shifted reading frame as a result of abnormalities in dystrophin gene. More specifically, the present invention relates to a splicing enhancer sequence (SES) in dystrophin gene which can be utilized for the preparation of pharmaceutical compositions for treatment of a specific type of Duchenne muscular dystrophy, as well as to antisense oligonucleotides against the splicing enhancer sequence, and therapeutic pharmaceutical compositions comprising such oligonucleotides. Diagnosis has become available today for hereditary diseases caused by abnormal splicing of pre-mRNA molecules. A so far intractable disease, muscular dystrophy, has thus come to draw particular attention. Muscular dystrophy is divided into two groups: Duchenne muscular dystrophy (DMD) and Becker muscular dystrophy (BMD). DMD is a hereditary muscular disease of the highest incidence, occurring in one in 3,500 live male births. Patients of DMD at first exhibit a lowered muscular power in their infancy, then suffer a constant progression of muscular atrophy thereafter, and eventually die at around the age of 20. It is in contrast to BMD, in which the onset of the disease is relatively late, somewhere in the adulthood, and though a mild loss of muscular power is observed after the onset of the disease, patients can live nearly a normal life. No drug is so far available for effective treatment of DMD, and therefore development of a drug for its treatment has been longed for by the patients across the world. In 1987, dystrophin gene, the causative gene of DMD, was found by means of retrospective genetics, and BMD also was found to result from abnormality in the same dystrophin gene [Koenig, M. et al., Cell, 50:509-517(1987)]. Dystrophin gene is located in the subregion 21 of the short arm of the X-chromosome. The size of the gene is 3.0 Mb, the largest known human gene. Despite that large size, only 14 kb regions in total of the dystrophin gene do encode the whole dystrophin protein, and those encoding regions are divided into no less than 79 exons which are distributed throughout the gene [Roberts, R G., et al., Genomics, 16:536-538(1993)]. The transcript of dystrophin gene, i.e. pre-mRNA, is spliced into the mature 14 kb mRNA. The gene has eight distinct promoter regions also distributed within the gene and they are responsible for production of distinct mRNAs, respectively [Nishio, H., et al., J. Clin. Invest., 94:10731042(1994), Ann, A H. and Kunkel, L M., Nature Genet., 3:283-291(1993), D'Souza, V N. et al., Hum. Mol. Genet., 4:837-842(1995)]. Thus, dystrophin gene and its transcript are structurally very complex. Web site: http://appft1.uspto.gov/netahtml/PTO/search-bool.html •
Treatment of muscular dystrophy with cord blood cells Inventor(s): Finklestein, Seth P. (Needham, MA), Brown, Robert H. JR. (Needham, MA) Correspondence: CLARK & ELBING LLP; 101 FEDERAL STREET; BOSTON; MA; 02110; US Patent Application Number: 20030118565 Date filed: July 23, 2002
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Abstract: The invention features methods for treating a patient suffering from muscular dystrophy by administration of umbilical cord blood cells, e.g., by IV infusion. Excerpt(s): This application claims the benefit of the filing date of U.S. provisional patent application No. 60/307,227, filed Jul. 23, 2001. Muscular dystrophy represents a family of inherited diseases of the muscles. Some forms affect children (e.g., Duchenne dystrophy) and are lethal within two to three decades. Other forms present in adult life and are more slowly progressive. The genes for several dystrophies have been identified, including Duchenne dystrophy (caused by mutations in the dystrophin gene) and the teenage and adult onset Miyoshi dystrophy or its variant, limb girdle dystrophy 2B or LGMD-2B (caused by mutations in the dysferlin gene). These are "loss of function" mutations that prevent expression of the relevant protein in muscle and thereby cause muscle dysfunction. Mouse models for these mutations exist, either arising spontaneously in nature or generated by inactivation or deletion of the relevant genes. These models are useful for testing therapies that might replace the missing protein in muscle and restore normal muscle function. Differentiated muscle is composed of multinucleated cells or myofibers that have an extraordinary capacity to regenerate. This regenerative capacity exists because muscle possesses primitive muscle precursor cells (muscle stem cells and somewhat more mature cells known as "satellite cells"). These cells lie dormant in muscle and can be activated to make new mononucleated muscle cells (myoblasts) that can adhere to one another and fuse to make new, multi-nucleated myotubes, as well as the more mature muscle cells (that are again multinucleated). Because myofibers arise from the fusion of individual myoblasts, a protein made by one muscle cell is readily accessible to be shared with neighboring muscle cells lacking that protein if the two cells fuse into the same myotube. 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 muscular dystrophy, 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 “muscular dystrophy” (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 muscular dystrophy. You can also use this procedure to view pending patent applications concerning muscular dystrophy. 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 MUSCULAR DYSTROPHY Overview This chapter provides bibliographic book references relating to muscular dystrophy. In addition to online booksellers such as www.amazon.com and www.bn.com, excellent sources for book titles on muscular dystrophy 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 “muscular dystrophy” (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 muscular dystrophy: •
A-Z Reference Book of Syndromes and Inherited Disorders Source: London, England: Chapman and Hall. 1996. 394 p. 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: $42.95 plus shipping and handling. ISBN: 0412641208. Summary: This book provides a practical reference for both caregivers and those with a syndrome or inherited disorder. The author describes the disorders and problems of both children and adults, and considers the day-to-day management of conditions. The book is written in nontechnical language while still providing enough detail for medical, nursing, and midwifery professionals. The syndromes and disorders are listed alphabetically by name. Those specifically related to deafness, communication, and
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speech and language include achondroplasia, Alport's syndrome, Apert's syndrome, Asperger's syndrome, Batten's disease, Beckwith-Wiedeman syndrome, CHARGE syndrome, Cockayne syndrome, Cornelia de Lange syndrome, Crouzon's syndrome, Down's syndrome, Duchenne muscular dystrophy, Edward's syndrome, Ehlers-Danlos syndrome, Fabry disease, fetal alcohol syndrome, Fragile X syndrome, Gilles de la Tourette syndrome, Goldenhar syndrome, Hunter's syndrome, Hurler's syndrome, Klinefelter's syndrome, LEOPARD syndrome, Moebius syndrome, Morquio's syndrome, neurofibromatosis, Niemann-Pick disease, Noonan's syndrome, osteogenesis imperfecta, Pierre-Robin syndrome, Prader-Willi syndrome, Rett's syndrome, Reye's syndrome, San Filippo syndrome, Smith-Magenis syndrome, Stickler syndrome, Tay-Sachs disease, Treacher Collins syndrome, Turner's syndrome, Usher's syndrome, Waardenburg's syndrome, and William's syndrome. For each syndrome, the author lists alternative names, incidence, causation (etiology), characteristics or symptoms, management implications (treatment options), prognosis, and self-help groups to contact. Most groups listed are in England. The book concludes with three appendices that provide a discussion of genetics, a listing of regional genetics centers (in England), and a glossary of terms. A subject index is also included. (AA-M).
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 “muscular dystrophy” at online booksellers’ Web sites, you may discover non-medical books that use the generic term “muscular dystrophy” (or a synonym) in their titles. The following is indicative of the results you might find when searching for “muscular dystrophy” (sorted alphabetically by title; follow the hyperlink to view more details at Amazon.com): •
Brenton's Story: An Autobiographical Account of One Man's Struggle with Muscular Dystrophy by Brenton Wilson, John Fitzgerald (Editor); ISBN: 0907324843; http://www.amazon.com/exec/obidos/ASIN/0907324843/icongroupinterna
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Cellular and molecular biology of muscle development : proceedings of a Muscular Dystrophy Association-UCLA Symposium, held at Steamboat Springs, Colorado, April 3-10, 1988; ISBN: 0845125516; http://www.amazon.com/exec/obidos/ASIN/0845125516/icongroupinterna
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Cellular and molecular biology of muscle development : proceedings of a Muscular Dystrophy Association-UCLA Symposium, held at Steamboat Springs, Colorado, April 3-10, 1988; ISBN: 084512692X; http://www.amazon.com/exec/obidos/ASIN/084512692X/icongroupinterna
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Child With Muscular Dystrophy in School by Nsnvy V. Dvhovk; ISBN: 9998492084; http://www.amazon.com/exec/obidos/ASIN/9998492084/icongroupinterna
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Congenital Muscular Dystrophies by Y. Fukuyama (Editor), et al; ISBN: 0444824871; http://www.amazon.com/exec/obidos/ASIN/0444824871/icongroupinterna
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Duchenne Muscular Dystrophy by Alan Emery, Francesco Muntoni (2003); ISBN: 0198515316; http://www.amazon.com/exec/obidos/ASIN/0198515316/icongroupinterna
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Duchenne Muscular Dystrophy (Oxford Medical Publicati Ons) by Alan E. H. Emery (1993); ISBN: 0192623702; http://www.amazon.com/exec/obidos/ASIN/0192623702/icongroupinterna
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Duchenne Muscular Dystrophy: Animal Models and Genetic Manipulation by Byron A. Kakulas (Editor), et al; ISBN: 0881679380; http://www.amazon.com/exec/obidos/ASIN/0881679380/icongroupinterna
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Experimental myopathies and muscular dystrophy : studies in the formal pathogenesis of the myopathy of 2, 4-dichlorophenoxyacetate by Rainer Heene; ISBN: 0387073760; http://www.amazon.com/exec/obidos/ASIN/0387073760/icongroupinterna
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Exploratory concepts in muscular dystrophy, II : control mechanisms in development and function of muscle and their relationship to muscular dystrophy and related neuromuscular diseases : proceedings of an international conference, Carefree, Arizona, October 15-19, 1973; ISBN: 0444150552; http://www.amazon.com/exec/obidos/ASIN/0444150552/icongroupinterna
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I Have Muscular Dystrophy (One World) by Brenda Pettenuzzo; ISBN: 0863138713; http://www.amazon.com/exec/obidos/ASIN/0863138713/icongroupinterna
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In good taste : a sampling of recipes from the best chefs of Wisconsin : to benefit the Muscular Dystrophy Association; ISBN: 0942495721; http://www.amazon.com/exec/obidos/ASIN/0942495721/icongroupinterna
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Living With Muscular Dystrophy: Illness Experience, Activities of Daily Living, Coping, Quality of Life & Rehabilitation (Comprehensive Summaries of Uppsala Dissertations from the Faculty of mediciNe, 1025) by Birgitta Natterlund, Brigitta Natterlund; ISBN: 9155449972; http://www.amazon.com/exec/obidos/ASIN/9155449972/icongroupinterna
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Molecular and Cell Biology of Muscular Dystrophy (Molecular and Cell Biology of Human Diseases, No 3) by Terence Partridge (Editor) (1993); ISBN: 0412434407; http://www.amazon.com/exec/obidos/ASIN/0412434407/icongroupinterna
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Moonrise: One Family, Genetic Identity, and Muscular Dystrophy by Penny Wolfson (Author) (2003); ISBN: 0312289081; http://www.amazon.com/exec/obidos/ASIN/0312289081/icongroupinterna
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Multiple Sclerosis, Muscular Dystrophy & Als (Dr. Donsbach Tells You What You Need to Know About) by Kurt W. Donsbach, H. Rudolph Alseleben (1993); ISBN: 1569595666; http://www.amazon.com/exec/obidos/ASIN/1569595666/icongroupinterna
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Muscular Dystrophy (A Venture Book) by James A. Corrick; ISBN: 0531125408; http://www.amazon.com/exec/obidos/ASIN/0531125408/icongroupinterna
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Muscular Dystrophy (Health Watch) by Gail Lemley Burnett, et al (2000); ISBN: 076601651X; http://www.amazon.com/exec/obidos/ASIN/076601651X/icongroupinterna
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Muscular dystrophy : biomedical aspects; ISBN: 4762263575; http://www.amazon.com/exec/obidos/ASIN/4762263575/icongroupinterna
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Muscular Dystrophy 1976: Proceedings of the Symposium on Muscular Dystrophy Held in Jerusalem, March-April 1976 by Gordon C. Robin (1977); ISBN: 3805526806; http://www.amazon.com/exec/obidos/ASIN/3805526806/icongroupinterna
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Muscular Dystrophy and Allied Diseases: Impact on Patients, Family, and Staff (Current Thanatology) by Leon I. Charash (Editor), et al (1988); ISBN: 0930194381; http://www.amazon.com/exec/obidos/ASIN/0930194381/icongroupinterna
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Muscular dystrophy and other inherited diseases of skeletal muscle in animals; ISBN: 0897660056; http://www.amazon.com/exec/obidos/ASIN/0897660056/icongroupinterna
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Muscular Dystrophy and Other Neuromuscular Disease: Psycholsocial Issues by Leon I. Charash, et al; ISBN: 1560240776; http://www.amazon.com/exec/obidos/ASIN/1560240776/icongroupinterna
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Muscular Dystrophy in Children: A Guide for Families by Irwin M. Siegel; ISBN: 1888799331; http://www.amazon.com/exec/obidos/ASIN/1888799331/icongroupinterna
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Muscular Dystrophy Research: Advances and New Trends (International Congress Vol 527) by Howard Griffin; ISBN: 044490168X; http://www.amazon.com/exec/obidos/ASIN/044490168X/icongroupinterna
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Muscular Dystrophy Research: From Molecular Diagnosis Toward Therapy: Proceedings (International Congress Series, No. 934) by A. Angelini, et al; ISBN: 044481406X; http://www.amazon.com/exec/obidos/ASIN/044481406X/icongroupinterna
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Muscular Dystrophy: Biomedical Aspects by S. and Ozawa, E. Ebashi (Editor), E. Ozawa (Editor); ISBN: 0387123423; http://www.amazon.com/exec/obidos/ASIN/0387123423/icongroupinterna
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Muscular Dystrophy: Methods and Protocols (Methods in Molecular Medicine, Number 43) by Katharine M. D. Bushby (Editor), et al; ISBN: 0896036952; http://www.amazon.com/exec/obidos/ASIN/0896036952/icongroupinterna
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Muscular Dystrophy: Proceedings of the International Symposium on Muscular Dystrophy, Held November 25-27, 1980 in Tokyo (Japan Medical Research Foundation Publication, No. 16) by International Symposium on Muscular Dystrophy, Setsuro Ebashi (Editor); ISBN: 0860083217; http://www.amazon.com/exec/obidos/ASIN/0860083217/icongroupinterna
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Muscular Dystrophy: The Facts (The Facts) by Alan E. H. Emery; ISBN: 0192624504; http://www.amazon.com/exec/obidos/ASIN/0192624504/icongroupinterna
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Myoblast Transfer: Gene Therapy for Muscular Dystrophy (Medical Intelligence Unit) by Peter K. Law; ISBN: 1879702762; http://www.amazon.com/exec/obidos/ASIN/1879702762/icongroupinterna
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Pathogenesis and Therapy of Duchenne and Becker Muscular Dystrophy by Byron A. Kakulas, Frank L. Mastaglia (Editor); ISBN: 0881675970; http://www.amazon.com/exec/obidos/ASIN/0881675970/icongroupinterna
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Pathogenesis of human muscular dystrophies : proceedings of the fifth International Scientific Conference of the Muscular Dystrophy Association, Durango, Colorado, June 21-25, 1976; ISBN: 0444152490; http://www.amazon.com/exec/obidos/ASIN/0444152490/icongroupinterna
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Precious Time: Children Living With Muscular Dystrophy (Don't Turn Away) by Thomas Bergman (Photographer) (1996); ISBN: 0836815971; http://www.amazon.com/exec/obidos/ASIN/0836815971/icongroupinterna
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Psychosocial Aspects of Muscular Dystrophy and Allied Diseases: Commitment to Life, Health, and Function by Leon I. Charash, et al; ISBN: 0398048118; http://www.amazon.com/exec/obidos/ASIN/0398048118/icongroupinterna
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Readings in Muscular Dystrophy by Douglas H. Ruben, Nancy R. MacCiomei (Editor); ISBN: 0582286581; http://www.amazon.com/exec/obidos/ASIN/0582286581/icongroupinterna
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Research in muscle development and the muscle spindle; proceedings of an international symposium sponsored by Muscular Dystrophy Associations of America, Inc., Northeastern Chapter at Cleveland Metropolitan General Hospital, Cleveland, Ohio, October 30-31, 1970; ISBN: 9021901730; http://www.amazon.com/exec/obidos/ASIN/9021901730/icongroupinterna
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Research into muscular dystrophy: the proceedings of the fourth Symposium on Current Research in Muscular Dystrophy, held at the National Hospital, Queen Square, London W.C. 1, 11th-12th January, 1968; ISBN: 0272792667; http://www.amazon.com/exec/obidos/ASIN/0272792667/icongroupinterna
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Research into the Origin and Treatment of Muscular Dystrophy (Current Clinical Practice, Vol 20) by L.P. Ten Kate, et al; ISBN: 0444904050; http://www.amazon.com/exec/obidos/ASIN/0444904050/icongroupinterna
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Research into the origin and treatment of muscular dystrophy : proceedings of a workshop held at "De Hooge Vuursche", Baarn, Holland, 24-27 February 1984; ISBN: 9021996715; http://www.amazon.com/exec/obidos/ASIN/9021996715/icongroupinterna
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Sixth Symposium on Current Research in Muscular Dystrophy and Related Diseases, held at University College, Gower Street, London, W.C. 1, 6-8 January, 1972: abstracts of communications; ISBN: 090356100X; http://www.amazon.com/exec/obidos/ASIN/090356100X/icongroupinterna
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Studies of Pseudohypertrophic Muscular Dystrophy by C. A. Bonsett; ISBN: 039800188X; http://www.amazon.com/exec/obidos/ASIN/039800188X/icongroupinterna
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The 2002 Official Patient's Sourcebook on Muscular Dystrophy by James N. Parker (Editor), Philip M. Parker (Editor) (2002); ISBN: 0597832102; http://www.amazon.com/exec/obidos/ASIN/0597832102/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 History of a Genetic Disease: Duchenne Muscular Dystrophy or Meryon's Disease by Alan E.H. Emery, Marcia L.H. Emery; ISBN: 1853152498; http://www.amazon.com/exec/obidos/ASIN/1853152498/icongroupinterna
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The Muscular Dystrophies by Alan E. H. Emery (Editor); ISBN: 0192632914; http://www.amazon.com/exec/obidos/ASIN/0192632914/icongroupinterna
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The Will to Live: The Battle of a Young Boy Against Muscular Dystrophy by A.J. Mills; ISBN: 0963392107; http://www.amazon.com/exec/obidos/ASIN/0963392107/icongroupinterna
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Ventilators and Muscular Dystrophy by Nancy C. Schock, Agatha P. Colbert (1987); ISBN: 0931301033; http://www.amazon.com/exec/obidos/ASIN/0931301033/icongroupinterna
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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 “muscular dystrophy” (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 •
A report on an experiment in camping for children with muscular dystrophy, September 1955. Author: Muscular Dystrophy Associations of America.; Year: 1974; New York [1956?]
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A report on the Liberty Muscular Dystrophy Research Foundation Symposium on Muscular Dystrophy, held at the Jesse H. Jones Memorial Library Building, Texas Medical Center, Houston, TEXAS, October 4 and 5, 1963. Author: Liberty Muscular Dystrophy Research Foundation.; Year: 1965; Galveston, Univ. of Texas Medical Branch, c1965
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An approach to the rehabilitation of children with muscular dystrophy; a symposium and a guide to physical therapy. Author: Abramson, Arthur Simon,; Year: 1955; [New York,
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Cause and prevention of poliomyelitis, arthritis, multiple sclerosis, and muscular dystrophy. Author: Warren, Nellie B.; Year: 1963; Hartford, Mich., 1954
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Experimental muscular dystrophies in animals; a comparative study, by Ira Rockwood Telford, in collaboration with Larus Einarson. Author: Telford, Ira Rockwood,; Year: 1971; Springfield, Ill., Thomas [c1971]
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Experimental myopathies and muscular dystrophy: studies in the formal pathogenesis of the myopathy of 2,4-dichlorophenoxyacetate Author: Heene, Rainer,; Year: 1975; Berlin; New York: Springer-Verlag, 1975; ISBN: 3540073760
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Exploratory concepts in muscular dystrophy and related disorders; proceedings of the international conference convened by Muscular Dystrophy Associations of America at Arden House, Harriman, New York, October 22-27, 1966. Editor: A. T. Milhorat. Author: Milhorat, Ade T.; Year: 1968; Amsterdam, New York, Excerpta Medica Foundation [1967]
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Genetic analysis of the X chromosome: studies of Duchenne muscular dystrophy and related disorders Author: Wolf, Stewart,; Year: 1957; New York: Plenum Press, c1982; ISBN: 0306411296 http://www.amazon.com/exec/obidos/ASIN/0306411296/icongroupinterna
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Muscular dystrophy research: advances and new trends: proceedings. Author: Angelini, C. (Corrado); Year: 1982; Amsterdam; Princeton, N.J.: Excerpta medica, 1980
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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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Muscular dystrophy. Author: National Institute of Neurological Diseases and Blindness (U.S.); Year: 1972; Bethesda, Md., For sale by the Supt. of Docs., U. S. Govt. Print. Off., Washington, 1968]
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Nutritional muscular dystrophy in cattle, with special reference to the functional state of the thyroid. Author: Andersson, Per.; Year: 1965; Copenhagen, Munksgaard, 1960
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Progressive muscular dystrophy; diagnosis and problems of rehabilitation [by] Chester A. Swinyard, George G. Deaver and Leon Greenspan. Author: Deaver, George G. (George Gilbert),; Year: 1956; New York [Muscular
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Progressive muscular dystrophy; diagnosis and problems of rehabilitation [by] George G. Deaver [and others. Author: Deaver, George G. (George Gilbert),; Year: 1958; New York, Institute of Physical Medicine and Rehabilitation, New York Univ.-Bellevue Medical Center, 1956]
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Providing assistance to certain non-Federal institutions for construction of facilities for research in crippling and killing diseases such as cancer, heart disease, poliomyelitis, nervous disorders, mental illness, arthritis and rheumatism, blindness, cerebral palsy, tuberculosis, multiple sclerosis, epilepsy, cystic fibrosis, and muscular dystrophy; report to accompany S. 849. Author: United States. Congress. Senate. Committee on Labor and Public Welfare.; Year: 1954; [Washington, 1955]
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Regeneration of striated muscle, and myogenesis; proceedings of the international conference convened by Muscular Dystrophy Associations of America at the Institute of Muscle Disease, New York, March 28-29 1969. Editors: Alexander Mauro, Saiyid A. Shafiq [and] Ade T. Milhorat. Author: Mauro, Alexander.; Year: 1963; Amsterdam, Excerpta medica, 1970; ISBN: 9021901420
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Research in muscular dystrophy: the proceedings of the Second Symposium on Current Research in Muscular Dystrophy held at the National Hospital, Queen Square, London. 3d-4th January 1963. Ed. by the members of the Research Committee ofthe Muscular Dystrophy Group. Author: Muscular Dystrophy Group of Great Britain.; Year: 1999; [London] Pitman [1963]
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Research in muscular dystrophy; proceedings. held at The National Hospital, London, 11th-12th January, 1968. Edited by the members of the Research Committee of the Muscular Dystrophy Group. Author: Muscular Dystrophy Group of Great Britain. Research Committee.; Year: 1969; [London] Pitman [c1968]
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The electric activity in resting muscle in progressive muscular dystrophy. Author: Amick, Lawrence Douglas,; Year: 1953; [Minneapolis] 1957
Chapters on Muscular Dystrophy In order to find chapters that specifically relate to muscular dystrophy, an excellent source of abstracts is the Combined Health Information Database. You will need to limit your search to book chapters and muscular dystrophy 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 “muscular dystrophy” (or synonyms) into the “For these words:” box. The following is a typical result when searching for book chapters on muscular dystrophy:
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Chapter 66: Muscular Dystrophy and Related Disorders Source: in Berkow, R., ed. The Merck Manual of Medical Information: Home Edition (online version). Rahway, NJ: Merck and Company, Inc. 2000. 6 p. Contact: Available online from Merck and Company, Inc. (800) 819-9456. Website: www.merck.com/pubs/mmanual_home/contents.htm. Also available from your local book store. PRICE: $29.95 plus shipping. Summary: This chapter provides the general public and people who have muscular dystrophy and related disorders with information on the symptoms, diagnosis, and treatment of these inherited muscle disorders. Duchenne's and Becker's muscular dystrophies, the most common forms, cause weakness in the muscles closest to the torso. The gene that causes these muscular dystrophies is recessive and is carried on the X chromosome. A female may carry the gene for these muscular dystrophies, but she does not have them because the normal X chromosome compensates for the gene defect on the other X chromosome; however, any male who receives the defective X chromosome will have the disease. Muscular dystrophy is suspected when a young boy becomes weak and grows weaker. A muscle biopsy is done to confirm the diagnosis. Neither form of muscular dystrophy can be cured. Physical therapy and exercise help prevent muscle contracture. Prednisone is being investigated as a means of temporarily relieving muscle weakness. Other muscular dystrophies include Landouzy-Dejerine, Leyden-Mobius, and Erb's muscular dystrophies and mitochondrial myopathies. Diagnosis is based on a muscle biopsy. Myotonic myopathies are a group of inherited disorders in which muscles are unable to relax normally after contraction. They include the autosomal dominant disorders myotonic dystrophy and myotonia congenita. Glycogen storage diseases are a related group of rare autosomal recessive inherited disorders in which muscles cannot metabolize sugars normally. Pompe's disease is the severest form of glycogen storage disease. Other forms of glycogen storage disease can cause mild to severe pain and weakness. Diagnosis of a glycogen storage disease is based on the measurement of myoglobin in the urine. Periodic paralysis, a rare autosomal dominant inherited disorder, involves sudden attacks of weakness and paralysis. The best clue to the diagnosis of these problems is the person's description of a typical attack. Checking the level of potassium while an attack is in progress is helpful. Acetazolamide may prevent attacks that are caused by either too much or too little potassium.
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Muscular Dystrophy: Duchenne Muscular Dystrophy, Becker Muscular Dystrophy Source: in Plumridge, D., et al., eds. Student with a Genetic Disorder: Educational Implications for Special Education Teachers and for Physical Therapists, Occupational Therapists, and Speech Pathologists. Springfield, IL: Charles C Thomas Publisher. 1993. p. 180-185. Contact: Available from Charles C Thomas Publisher. 2600 South First Street, Springfield, IL 62794-9265. (212) 789-8980. Fax (217) 789-9130. PRICE: $75.95 plus shipping and handling (cloth); $39.95 plus shipping and handling (paper). ISBN: 0398058393. Summary: Both Duchenne and Becker muscular dystrophy are progressive muscle wasting conditions that primarily affect boys. This chapter on muscular dystrophy is from a text for special education teachers, physical therapists, occupational therapists, and speech pathologists on the educational implications of genetic disorders. Topics covered include the physical and characteristic features of the disorder, the genetics of the disorder, the cognitive and behavior profiles, the educational implications, physical
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therapy, occupational therapy, hearing and speech considerations, psychosocial issues, and prognosis. 5 references. •
Myotonic Dystrophy: Steinert Muscular Dystrophy, Dytrophia Myotonica Source: in Plumridge, D., et al., eds. Student with a Genetic Disorder: Educational Implications for Special Education Teachers and for Physical Therapists, Occupational Therapists, and Speech Pathologists. Springfield, IL: Charles C Thomas Publisher. 1993. p. 186-191. Contact: Available from Charles C Thomas Publisher. 2600 South First Street, Springfield, IL 62794-9265. (217) 789-8980. Fax (217) 789-9130. PRICE: $75.95 plus shipping and handling (cloth); $39.95 plus shipping and handling (paper). ISBN: 0398058393. Summary: Myotonic dystrophy is a type of muscular dystrophy that affects other parts of the body in addition to muscles. This chapter on myotonic dystrophy is from a text for special education teachers, physical therapists, occupational therapists, and speech pathologists on the educational implications of genetic disorders. Topics covered include the physical and characteristic features of the disorder, the genetics of the disorder, the cognitive and behavior profiles, the educational implications, physical therapy, occupational therapy, hearing and speech considerations, psychosocial issues, and prognosis. 6 references.
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CHAPTER 8. MULTIMEDIA ON MUSCULAR DYSTROPHY Overview In this chapter, we show you how to keep current on multimedia sources of information on muscular dystrophy. 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 Muscular Dystrophy 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 muscular dystrophy (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 muscular dystrophy: •
Duchenne's pseudohypertrophic muscular dystrophy [slide] Source: authors, Lynette Chandler, Shari Freshman, Jeanne Fischer; produced by Division of Physical Therapy, Dept. of Rehabilitation Medicine and Health Sciences Learning Resources Center, University of; Year: 1981; Format: Slide; [Seattle, Wash.]: The Division, c1981
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Muscular dystrophy [filmstrip] Source: Trainex Corporation; Year: 1973; Format: Filmstrip; Garden Grove, Calif: Trainex, c1973
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Muscular dystrophy [slide] Source: Donald L. Schotland; Year: 1971; Format: Slide; [New York]: Medcom, c1971
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Muscular dystrophy [slide] Source: the American Academy of Orthopaedic Surgeons; Year: 1976; Format: Slide; [Chicago, Ill.]: The Academy, [1976]
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Muscular dystrophy [videorecording] Source: Trainex Corporation; Year: 1973; Format: Videorecording; Garden Grove, Calif.: Trainex, c1973
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Muscular dystrophy [videorecording] Source: a Films for the Humanities and Sciences presentation; a production of the Dartmouth-Hitchcock Medical Center; Year: 1990; Format: Videorecording; Princeton, N.J.: Film for the Humanities & Sciences, c1990
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Muscular dystrophy and related conditions [motion picture]: differential diagnosis Source: Muscular Dystrophy Associations of America; produced by Sturgis-Grant Productions; Year: 1966; Format: Motion picture; New York: The Associations; [Atlanta: for loan by National Medical Audiovisual Center], 1966
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Muscular dystrophy, the race for the gene [videorecording] Source: a BBC TV production for the Open University, in association with Coronet/MTI Film and Video; Year: 1987; Format: Videorecording; [London, England]: Open University, c1987
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CHAPTER 9. PERIODICALS AND NEWS ON MUSCULAR DYSTROPHY Overview In this chapter, we suggest a number of news sources and present various periodicals that cover muscular dystrophy.
News Services and Press Releases One of the simplest ways of tracking press releases on muscular dystrophy 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 “muscular dystrophy” (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 muscular dystrophy. 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 “muscular dystrophy” (or synonyms). The following was recently listed in this archive for muscular dystrophy: •
Stem cells offer hope for muscular dystrophy Source: Reuters Health eLine Date: July 11, 2003 http://www.reutershealth.com/archive/2003/07/11/eline/links/20030711elin006.htm l
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Cell therapy with mesoangioblasts may ameliorate muscular dystrophy Source: Reuters Industry Breifing Date: July 11, 2003
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New approach repairs genetic defect in Duchenne muscular dystrophy mouse model Source: Reuters Medical News Date: July 07, 2003
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Cell membrane repair deficient in some muscular dystrophies Source: Reuters Medical News Date: May 08, 2003
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Growth hormone ameliorates muscular dystrophy-related cardiomyopathy Source: Reuters Industry Breifing Date: April 16, 2003
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First evidence presented that gene transfer can treat muscular dystrophy Source: Reuters Industry Breifing Date: September 17, 2002
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Researchers fix muscular dystrophy damage in mice Source: Reuters Health eLine Date: September 16, 2002
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Gene problem in muscular dystrophy identified Source: Reuters Health eLine Date: August 08, 2002
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"Valley sign" a new diagnostic tool for Duchenne muscular dystrophy Source: Reuters Medical News Date: July 29, 2002
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Clues to muscular dystrophy revealed Source: Reuters Health eLine Date: July 25, 2002
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Mouse study shows enzyme helps muscular dystrophy Source: Reuters Health eLine Date: April 19, 2002
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Gene therapy studied for muscular dystrophy Source: Reuters Health eLine Date: December 12, 2001
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Axcell, Mount Sinai in Alzheimer's, muscular dystrophy protein research pact Source: Reuters Industry Breifing Date: November 15, 2001
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House approves muscular dystrophy research push Source: Reuters Medical News Date: September 25, 2001
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House approves muscular dystrophy funding bill Source: Reuters Industry Breifing Date: September 25, 2001
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Mini-protein restores muscle function in murine model of muscular dystrophy Source: Reuters Industry Breifing Date: September 19, 2001
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Gene therapy fights muscular dystrophy in mice Source: Reuters Health eLine Date: September 19, 2001
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Genetic cause found for type of muscular dystrophy Source: Reuters Medical News Date: August 03, 2001
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Gene mutation linked to form of muscular dystrophy Source: Reuters Health eLine Date: August 02, 2001
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FDA pulls fast track status from muscular dystrophy study Source: Reuters Industry Breifing Date: May 01, 2001
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Key signaling mechanism could point to muscular dystrophy treatment Source: Reuters Medical News Date: April 27, 2001
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Benefit seen with long-term deflazacort for Duchenne muscular dystrophy Source: Reuters Industry Breifing Date: February 27, 2001
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Muscular dystrophy gene therapy works in mice Source: Reuters Health eLine Date: February 23, 2001
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Muscle growth factor might treat age-related muscle wasting, muscular dystrophy Source: Reuters Industry Breifing Date: February 08, 2001
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Verapamil prevents cardiomyopathy in mice with limb-girdle muscular dystrophy Source: Reuters Medical News Date: January 23, 2001
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Gene therapy for muscular dystrophy promising Source: Reuters Health eLine Date: November 30, 2000
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Repeats in muscular dystrophy gene responsible for disease in mice Source: Reuters Industry Breifing Date: September 11, 2000
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Unusual mutation linked to muscular dystrophy Source: Reuters Health eLine Date: September 07, 2000
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Chimeric oligonucleotide repairs mutation in dog model of muscular dystrophy Source: Reuters Medical News Date: June 02, 2000
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Gene therapy repairs DNA in dog with muscular dystrophy Source: Reuters Health eLine Date: May 30, 2000
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Gene therapy successful in hamster model of limb girdle muscular dystrophy Source: Reuters Medical News Date: February 07, 2000
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Gene for novel sarcomeric protein may be involved in muscular dystrophy Source: Reuters Medical News Date: December 17, 1999
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Muscular dystrophy gene linked to heart disorder Source: Reuters Health eLine Date: December 02, 1999
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Stem cell transplantation restores dystrophin in mouse muscular dystrophy model Source: Reuters Medical News Date: September 23, 1999
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Bone marrow transplantation for muscular dystrophy Source: Reuters Health eLine Date: September 22, 1999
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Loss of nitric-oxide signaling linked to etiology of muscular dystrophy Source: Reuters Medical News Date: August 16, 1999
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Muscular dystrophy may be treatable in some mice Source: Reuters Health eLine Date: July 29, 1999
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Sarcoglycan protein deficiency causes muscular dystrophy in mouse model Source: Reuters Medical News Date: December 17, 1998
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Full-length utrophin expression needed to prevent muscular dystrophy in mice Source: Reuters Medical News Date: December 14, 1998
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New clue to muscular dystrophy Source: Reuters Health eLine Date: December 07, 1998
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Gene associated with two types of muscular dystrophy identified Source: Reuters Medical News Date: September 03, 1998
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Gene plays role in muscular dystrophies Source: Reuters Health eLine Date: September 02, 1998
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Utrophin Transgene Corrects Clinical Signs Of Muscular Dystrophy In Mouse Model Of The Disease Source: Reuters Medical News Date: April 28, 1998
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Duchenne Muscular Dystrophy: Noninvasive Respiratory Protocol Effective Source: Reuters Medical News Date: October 31, 1997
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Duchenne Muscular Dystrophy: A Better Mouse Model Built Source: Reuters Medical News Date: August 25, 1997
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New Protein May Fight Muscular Dystrophy Source: Reuters Health eLine Date: December 04, 1996
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Upregulation Of Utrophin Relieves Muscular Dystrophy In Mice Source: Reuters Medical News Date: November 28, 1996
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Gene Therapy For Muscular Dystrophy Source: Reuters Health eLine Date: September 04, 1996
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Dystrophin Gene Transfer Successful In Mice With Muscular Dystrophy Source: Reuters Medical News Date: September 03, 1996
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Myocardial Damage Common In Carriers Of Muscular Dystrophies Source: Reuters Medical News Date: May 07, 1996 The NIH
Within MEDLINEplus, the NIH has made an agreement with the New York Times Syndicate, the AP News Service, and Reuters to deliver news that can be browsed by the public. Search news releases at http://www.nlm.nih.gov/medlineplus/alphanews_a.html. MEDLINEplus allows you to browse across an alphabetical index. Or you can search by date at the following Web page: http://www.nlm.nih.gov/medlineplus/newsbydate.html. Often, news items are indexed by MEDLINEplus within its search engine. Business Wire Business Wire is similar to PR Newswire. To access this archive, simply go to http://www.businesswire.com/. You can scan the news by industry category or company name. Market Wire Market Wire is more focused on technology than the other wires. To browse the latest press releases by topic, such as alternative medicine, biotechnology, fitness, healthcare, legal, nutrition, and pharmaceuticals, access Market Wire’s Medical/Health channel at http://www.marketwire.com/mw/release_index?channel=MedicalHealth. Or simply go to Market Wire’s home page at http://www.marketwire.com/mw/home, type “muscular dystrophy” (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.
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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 “muscular dystrophy” (or synonyms). If you know the name of a company that is relevant to muscular dystrophy, 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 “muscular dystrophy” (or synonyms).
Academic Periodicals covering Muscular Dystrophy Numerous periodicals are currently indexed within the National Library of Medicine’s PubMed database that are known to publish articles relating to muscular dystrophy. In addition to these sources, you can search for articles covering muscular dystrophy that have been published by any of the periodicals listed in previous chapters. To find the latest studies published, go to http://www.ncbi.nlm.nih.gov/pubmed, type the name of the periodical into the search box, and click “Go.” If you want complete details about the historical contents of a journal, you can also visit the following Web site: http://www.ncbi.nlm.nih.gov/entrez/jrbrowser.cgi. Here, type in the name of the journal or its abbreviation, and you will receive an index of published articles. At http://locatorplus.gov/, you can retrieve more indexing information on medical periodicals (e.g. the name of the publisher). Select the button “Search LOCATORplus.” Then type in the name of the journal and select the advanced search option “Journal Title Search.”
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APPENDICES
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APPENDIX A. PHYSICIAN RESOURCES Overview In this chapter, we focus on databases and Internet-based guidelines and information resources created or written for a professional audience.
NIH Guidelines Commonly referred to as “clinical” or “professional” guidelines, the National Institutes of Health publish physician guidelines for the most common diseases. Publications are available at the following by relevant Institute12: •
Office of the Director (OD); guidelines consolidated across agencies available at http://www.nih.gov/health/consumer/conkey.htm
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National Institute of General Medical Sciences (NIGMS); fact sheets available at http://www.nigms.nih.gov/news/facts/
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National Library of Medicine (NLM); extensive encyclopedia (A.D.A.M., Inc.) with guidelines: http://www.nlm.nih.gov/medlineplus/healthtopics.html
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National Cancer Institute (NCI); guidelines available at http://www.cancer.gov/cancerinfo/list.aspx?viewid=5f35036e-5497-4d86-8c2c714a9f7c8d25
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National Eye Institute (NEI); guidelines available at http://www.nei.nih.gov/order/index.htm
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National Heart, Lung, and Blood Institute (NHLBI); guidelines available at http://www.nhlbi.nih.gov/guidelines/index.htm
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National Human Genome Research Institute (NHGRI); research available at http://www.genome.gov/page.cfm?pageID=10000375
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National Institute on Aging (NIA); guidelines available at http://www.nia.nih.gov/health/
12
These publications are typically written by one or more of the various NIH Institutes.
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•
National Institute on Alcohol Abuse and Alcoholism (NIAAA); guidelines available at http://www.niaaa.nih.gov/publications/publications.htm
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National Institute of Allergy and Infectious Diseases (NIAID); guidelines available at http://www.niaid.nih.gov/publications/
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National Institute of Arthritis and Musculoskeletal and Skin Diseases (NIAMS); fact sheets and guidelines available at http://www.niams.nih.gov/hi/index.htm
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National Institute of Child Health and Human Development (NICHD); guidelines available at http://www.nichd.nih.gov/publications/pubskey.cfm
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National Institute on Deafness and Other Communication Disorders (NIDCD); fact sheets and guidelines at http://www.nidcd.nih.gov/health/
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National Institute of Dental and Craniofacial Research (NIDCR); guidelines available at http://www.nidr.nih.gov/health/
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National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK); guidelines available at http://www.niddk.nih.gov/health/health.htm
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National Institute on Drug Abuse (NIDA); guidelines available at http://www.nida.nih.gov/DrugAbuse.html
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National Institute of Environmental Health Sciences (NIEHS); environmental health information available at http://www.niehs.nih.gov/external/facts.htm
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National Institute of Mental Health (NIMH); guidelines available at http://www.nimh.nih.gov/practitioners/index.cfm
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National Institute of Neurological Disorders and Stroke (NINDS); neurological disorder information pages available at http://www.ninds.nih.gov/health_and_medical/disorder_index.htm
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National Institute of Nursing Research (NINR); publications on selected illnesses at http://www.nih.gov/ninr/news-info/publications.html
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National Institute of Biomedical Imaging and Bioengineering; general information at http://grants.nih.gov/grants/becon/becon_info.htm
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Center for Information Technology (CIT); referrals to other agencies based on keyword searches available at http://kb.nih.gov/www_query_main.asp
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National Center for Complementary and Alternative Medicine (NCCAM); health information available at http://nccam.nih.gov/health/
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National Center for Research Resources (NCRR); various information directories available at http://www.ncrr.nih.gov/publications.asp
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Office of Rare Diseases; various fact sheets available at http://rarediseases.info.nih.gov/html/resources/rep_pubs.html
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Centers for Disease Control and Prevention; various fact sheets on infectious diseases available at http://www.cdc.gov/publications.htm
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NIH Databases In addition to the various Institutes of Health that publish professional guidelines, the NIH has designed a number of databases for professionals.13 Physician-oriented resources provide a wide variety of information related to the biomedical and health sciences, both past and present. The format of these resources varies. Searchable databases, bibliographic citations, full-text articles (when available), archival collections, and images are all available. The following are referenced by the National Library of Medicine:14 •
Bioethics: Access to published literature on the ethical, legal, and public policy issues surrounding healthcare and biomedical research. This information is provided in conjunction with the Kennedy Institute of Ethics located at Georgetown University, Washington, D.C.: http://www.nlm.nih.gov/databases/databases_bioethics.html
•
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/
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Population Information: The National Library of Medicine provides access to worldwide coverage of population, family planning, and related health issues, including family planning technology and programs, fertility, and population law and policy: http://www.nlm.nih.gov/databases/databases_population.html
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Cancer Information: Access to cancer-oriented databases: http://www.nlm.nih.gov/databases/databases_cancer.html
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Profiles in Science: Offering the archival collections of prominent twentieth-century biomedical scientists to the public through modern digital technology: http://www.profiles.nlm.nih.gov/
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Chemical Information: Provides links to various chemical databases and references: http://sis.nlm.nih.gov/Chem/ChemMain.html
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Clinical Alerts: Reports the release of findings from the NIH-funded clinical trials where such release could significantly affect morbidity and mortality: http://www.nlm.nih.gov/databases/alerts/clinical_alerts.html
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Space Life Sciences: Provides links and information to space-based research (including NASA): http://www.nlm.nih.gov/databases/databases_space.html
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MEDLINE: Bibliographic database covering the fields of medicine, nursing, dentistry, veterinary medicine, the healthcare system, and the pre-clinical sciences: http://www.nlm.nih.gov/databases/databases_medline.html
13
Remember, for the general public, the National Library of Medicine recommends the databases referenced in MEDLINEplus (http://medlineplus.gov/ or http://www.nlm.nih.gov/medlineplus/databases.html). 14 See http://www.nlm.nih.gov/databases/databases.html.
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Toxicology and Environmental Health Information (TOXNET): Databases covering toxicology and environmental health: http://sis.nlm.nih.gov/Tox/ToxMain.html
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Visible Human Interface: Anatomically detailed, three-dimensional representations of normal male and female human bodies: http://www.nlm.nih.gov/research/visible/visible_human.html
The NLM Gateway15 The NLM (National Library of Medicine) Gateway is a Web-based system that lets users search simultaneously in multiple retrieval systems at the U.S. National Library of Medicine (NLM). It allows users of NLM services to initiate searches from one Web interface, providing one-stop searching for many of NLM’s information resources or databases.16 To use the NLM Gateway, simply go to the search site at http://gateway.nlm.nih.gov/gw/Cmd. Type “muscular dystrophy” (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 17938 217 85 5 0 18245
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 “muscular dystrophy” (or synonyms) at the following Web site: http://text.nlm.nih.gov.
15
Adapted from NLM: http://gateway.nlm.nih.gov/gw/Cmd?Overview.x.
16
The NLM Gateway is currently being developed by the Lister Hill National Center for Biomedical Communications (LHNCBC) at the National Library of Medicine (NLM) of the National Institutes of Health (NIH). 17 Adapted from HSTAT: http://www.nlm.nih.gov/pubs/factsheets/hstat.html. 18 19
The HSTAT URL is http://hstat.nlm.nih.gov/.
Other important documents in HSTAT include: the National Institutes of Health (NIH) Consensus Conference Reports and Technology Assessment Reports; the HIV/AIDS Treatment Information Service (ATIS) resource documents; the Substance Abuse and Mental Health Services Administration's Center for Substance Abuse Treatment (SAMHSA/CSAT) Treatment Improvement Protocols (TIP) and Center for Substance Abuse Prevention (SAMHSA/CSAP) Prevention Enhancement Protocols System (PEPS); the Public Health Service (PHS) Preventive Services Task Force's Guide to Clinical Preventive Services; the independent, nonfederal Task Force on Community Services’ Guide to Community Preventive Services; and the Health Technology Advisory Committee (HTAC) of the Minnesota Health Care Commission (MHCC) health technology evaluations.
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Coffee Break: Tutorials for Biologists20 Coffee Break is a general healthcare site that takes a scientific view of the news and covers recent breakthroughs in biology that may one day assist physicians in developing treatments. Here you will find a collection of short reports on recent biological discoveries. Each report incorporates interactive tutorials that demonstrate how bioinformatics tools are used as a part of the research process. Currently, all Coffee Breaks are written by NCBI staff.21 Each report is about 400 words and is usually based on a discovery reported in one or more articles from recently published, peer-reviewed literature.22 This site has new articles every few weeks, so it can be considered an online magazine of sorts. It is intended for general background information. You can access the Coffee Break Web site at the following hyperlink: http://www.ncbi.nlm.nih.gov/Coffeebreak/.
Other Commercial Databases In addition to resources maintained by official agencies, other databases exist that are commercial ventures addressing medical professionals. Here are some examples that may interest you: •
CliniWeb International: Index and table of contents to selected clinical information on the Internet; see http://www.ohsu.edu/cliniweb/.
•
Medical World Search: Searches full text from thousands of selected medical sites on the Internet; see http://www.mwsearch.com/.
The Genome Project and Muscular Dystrophy In the following section, we will discuss databases and references which relate to the Genome Project and muscular dystrophy. Online Mendelian Inheritance in Man (OMIM) The Online Mendelian Inheritance in Man (OMIM) database is a catalog of human genes and genetic disorders authored and edited by Dr. Victor A. McKusick and his colleagues at Johns Hopkins and elsewhere. OMIM was developed for the World Wide Web by the National Center for Biotechnology Information (NCBI).23 The database contains textual information, pictures, and reference information. It also contains copious links to NCBI’s Entrez database of MEDLINE articles and sequence information. 20 Adapted 21
from http://www.ncbi.nlm.nih.gov/Coffeebreak/Archive/FAQ.html.
The figure that accompanies each article is frequently supplied by an expert external to NCBI, in which case the source of the figure is cited. The result is an interactive tutorial that tells a biological story. 22 After a brief introduction that sets the work described into a broader context, the report focuses on how a molecular understanding can provide explanations of observed biology and lead to therapies for diseases. Each vignette is accompanied by a figure and hypertext links that lead to a series of pages that interactively show how NCBI tools and resources are used in the research process. 23 Adapted from http://www.ncbi.nlm.nih.gov/. Established in 1988 as a national resource for molecular biology information, NCBI creates public databases, conducts research in computational biology, develops software tools for analyzing genome data, and disseminates biomedical information--all for the better understanding of molecular processes affecting human health and disease.
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To search the database, go to http://www.ncbi.nlm.nih.gov/Omim/searchomim.html. Type “muscular dystrophy” (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 muscular dystrophy: •
Aminoaciduria with Mental Deficiency, Dwarfism, Muscular Dystrophy, Osteoporosis, and Acidosis Web site: http://www.ncbi.nlm.nih.gov/htbin-post/Omim/dispmim?204730
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Emery-dreifuss Muscular Dystrophy Web site: http://www.ncbi.nlm.nih.gov/htbin-post/Omim/dispmim?310300
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Emery-dreifuss Muscular Dystrophy, Autosomal Dominant Web site: http://www.ncbi.nlm.nih.gov/htbin-post/Omim/dispmim?181350
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Emery-dreifuss Muscular Dystrophy, Autosomal Recessive Web site: http://www.ncbi.nlm.nih.gov/htbin-post/Omim/dispmim?604929
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Epidermolysis Bullosa Simplex and Limb-girdle Muscular Dystrophy Web site: http://www.ncbi.nlm.nih.gov/htbin-post/Omim/dispmim?226670
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Facioscapulohumeral Muscular Dystrophy 1a Web site: http://www.ncbi.nlm.nih.gov/htbin-post/Omim/dispmim?158900
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Facioscapulohumeral Muscular Dystrophy 1b Web site: http://www.ncbi.nlm.nih.gov/htbin-post/Omim/dispmim?158901
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Facioscapulohumeral Muscular Dystrophy Region Gene 1 Web site: http://www.ncbi.nlm.nih.gov/htbin-post/Omim/dispmim?601278
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Fukuyama Congenital Muscular Dystrophy Web site: http://www.ncbi.nlm.nih.gov/htbin-post/Omim/dispmim?253800
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Mental Retardation, Scapuloperoneal Muscular Dystrophy, and Cardiomyopathy Web site: http://www.ncbi.nlm.nih.gov/htbin-post/Omim/dispmim?309660
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Muscular Dystrophy, Adult-onset, with Leukoencephalopathy Web site: http://www.ncbi.nlm.nih.gov/htbin-post/Omim/dispmim?253590
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Muscular Dystrophy, Barnes Type Web site: http://www.ncbi.nlm.nih.gov/htbin-post/Omim/dispmim?158800
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Muscular Dystrophy, Becker Type Web site: http://www.ncbi.nlm.nih.gov/htbin-post/Omim/dispmim?300376
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Muscular Dystrophy, Cardiac Type Web site: http://www.ncbi.nlm.nih.gov/htbin-post/Omim/dispmim?309930
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Muscular Dystrophy, Congenital Merosin-deficient, 1a Web site: http://www.ncbi.nlm.nih.gov/htbin-post/Omim/dispmim?607855
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Muscular Dystrophy, Congenital, 1b Web site: http://www.ncbi.nlm.nih.gov/htbin-post/Omim/dispmim?604801
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Muscular Dystrophy, Congenital, 1c Web site: http://www.ncbi.nlm.nih.gov/htbin-post/Omim/dispmim?606612
Lethal
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Muscular Dystrophy, Congenital, Eichsfeld Type Web site: http://www.ncbi.nlm.nih.gov/htbin-post/Omim/dispmim?253850
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Muscular Dystrophy, Congenital, Megaconial Type Web site: http://www.ncbi.nlm.nih.gov/htbin-post/Omim/dispmim?602541
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Muscular Dystrophy, Congenital, Producing Arthrogryposis Web site: http://www.ncbi.nlm.nih.gov/htbin-post/Omim/dispmim?253900
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Muscular Dystrophy, Congenital, with Cerebellar Atrophy Web site: http://www.ncbi.nlm.nih.gov/htbin-post/Omim/dispmim?603323
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Muscular Dystrophy, Congenital, with Infantile Cataract and Hypogonadism Web site: http://www.ncbi.nlm.nih.gov/htbin-post/Omim/dispmim?254000
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Muscular Dystrophy, Congenital, with Rapid Progression Web site: http://www.ncbi.nlm.nih.gov/htbin-post/Omim/dispmim?254100
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Muscular Dystrophy, Congenital, with Severe Central Nervous System Atrophy and Absence of Large Myelinated Fibers Web site: http://www.ncbi.nlm.nih.gov/htbin-post/Omim/dispmim?601170
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Muscular Dystrophy, Duchenne Type Web site: http://www.ncbi.nlm.nih.gov/htbin-post/Omim/dispmim?310200
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Muscular Dystrophy, Hemizygous Lethal Type Web site: http://www.ncbi.nlm.nih.gov/htbin-post/Omim/dispmim?309950
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Muscular Dystrophy, Limb-girdle, Autosomal Recessive Web site: http://www.ncbi.nlm.nih.gov/htbin-post/Omim/dispmim?601173
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Muscular Dystrophy, Limb-girdle, Type 1a Web site: http://www.ncbi.nlm.nih.gov/htbin-post/Omim/dispmim?159000
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Muscular Dystrophy, Limb-girdle, Type 1b Web site: http://www.ncbi.nlm.nih.gov/htbin-post/Omim/dispmim?159001
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Muscular Dystrophy, Limb-girdle, Type 1c Web site: http://www.ncbi.nlm.nih.gov/htbin-post/Omim/dispmim?607801
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Muscular Dystrophy, Limb-girdle, Type 1d Web site: http://www.ncbi.nlm.nih.gov/htbin-post/Omim/dispmim?603511
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Muscular Dystrophy, Limb-girdle, Type 2a Web site: http://www.ncbi.nlm.nih.gov/htbin-post/Omim/dispmim?253600
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Muscular Dystrophy, Limb-girdle, Type 2b Web site: http://www.ncbi.nlm.nih.gov/htbin-post/Omim/dispmim?253601
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Muscular Dystrophy, Limb-girdle, Type 2c Web site: http://www.ncbi.nlm.nih.gov/htbin-post/Omim/dispmim?253700
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Muscular Dystrophy, Limb-girdle, Type 2d Web site: http://www.ncbi.nlm.nih.gov/htbin-post/Omim/dispmim?608099
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Muscular Dystrophy, Limb-girdle, Type 2e Web site: http://www.ncbi.nlm.nih.gov/htbin-post/Omim/dispmim?604286
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Muscular Dystrophy, Limb-girdle, Type 2f Web site: http://www.ncbi.nlm.nih.gov/htbin-post/Omim/dispmim?601287
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Muscular Dystrophy, Limb-girdle, Type 2g Web site: http://www.ncbi.nlm.nih.gov/htbin-post/Omim/dispmim?601954
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Muscular Dystrophy, Limb-girdle, Type 2h Web site: http://www.ncbi.nlm.nih.gov/htbin-post/Omim/dispmim?254110
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Muscular Dystrophy, Limb-girdle, Type 2i Web site: http://www.ncbi.nlm.nih.gov/htbin-post/Omim/dispmim?607155
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Muscular Dystrophy, Mabry Type Web site: http://www.ncbi.nlm.nih.gov/htbin-post/Omim/dispmim?310000
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Muscular Dystrophy, Oculopharyngeal, Autosomal Recessive Web site: http://www.ncbi.nlm.nih.gov/htbin-post/Omim/dispmim?257950
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Muscular Dystrophy, Progressive Pectorodorsal Web site: http://www.ncbi.nlm.nih.gov/htbin-post/Omim/dispmim?310095
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Muscular Dystrophy, Pseudohypertrophic, with Internalized Capillaries Web site: http://www.ncbi.nlm.nih.gov/htbin-post/Omim/dispmim?159050
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Muscular Dystrophy, Scapulohumeral Web site: http://www.ncbi.nlm.nih.gov/htbin-post/Omim/dispmim?600416
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Muscular Dystrophy, Scleroatonic Web site: http://www.ncbi.nlm.nih.gov/htbin-post/Omim/dispmim?254090
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Oculopharyngeal Muscular Dystrophy Web site: http://www.ncbi.nlm.nih.gov/htbin-post/Omim/dispmim?164300
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Rigid Spine Muscular Dystrophy 1 Web site: http://www.ncbi.nlm.nih.gov/htbin-post/Omim/dispmim?602771
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Tibial Muscular Dystrophy, Tardive Web site: http://www.ncbi.nlm.nih.gov/htbin-post/Omim/dispmim?600334 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,
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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
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Genome: Complete genome assemblies, Web site: http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=Genome
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NCBI’s Protein Sequence Information Survey Results: Web site: http://www.ncbi.nlm.nih.gov/About/proteinsurvey/
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Nucleotide Sequence Database (Genbank): Web site: http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=Nucleotide
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OMIM: Online Mendelian Inheritance in Man, Web site: http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=OMIM
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PopSet: Population study data sets, Web site: http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=Popset
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ProbeSet: Gene Expression Omnibus (GEO), Web site: http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=geo
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Protein Sequence Database: Web site: http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=Protein
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PubMed: Biomedical literature (PubMed), Web site: http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed
•
Structure: Three-dimensional macromolecular structures, Web site: http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=Structure
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Taxonomy: Organisms in GenBank, Web site: http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=Taxonomy
To access the Entrez system at the National Center for Biotechnology Information, go to http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?CMD=search&DB=genome, and then select the database that you would like to search. The databases available are listed in the drop box next to “Search.” Enter “muscular dystrophy” (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. 24 Adapted from the National Library of Medicine: http://www.nlm.nih.gov/mesh/jablonski/about_syndrome.html. 25 Adapted from the Genome Database: http://gdbwww.gdb.org/gdb/aboutGDB.html - mission.
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To access the GDB, simply go to the following hyperlink: http://www.gdb.org/. Search “All Biological Data” by “Keyword.” Type “muscular dystrophy” (or synonyms) into the search box, and review the results. If more than one word is used in the search box, then separate each one with the word “and” or “or” (using “or” might be useful when using synonyms).
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APPENDIX B. PATIENT RESOURCES Overview Official agencies, as well as federally funded institutions supported by national grants, frequently publish a variety of guidelines written with the patient in mind. These are typically called “Fact Sheets” or “Guidelines.” They can take the form of a brochure, information kit, pamphlet, or flyer. Often they are only a few pages in length. Since new guidelines on muscular dystrophy can appear at any moment and be published by a number of sources, the best approach to finding guidelines is to systematically scan the Internet-based services that post them.
Patient Guideline Sources The remainder of this chapter directs you to sources which either publish or can help you find additional guidelines on topics related to muscular dystrophy. 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 muscular dystrophy. 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 “muscular dystrophy”:
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Other guides Amyotrophic Lateral Sclerosis http://www.nlm.nih.gov/medlineplus/amyotrophiclateralsclerosis.html Charcot-Marie-Tooth Disease http://www.nlm.nih.gov/medlineplus/charcotmarietoothdisease.html Degenerative Nerve Diseases http://www.nlm.nih.gov/medlineplus/degenerativenervediseases.html Dwarfism http://www.nlm.nih.gov/medlineplus/dwarfism.html Genetic Brain Disorders http://www.nlm.nih.gov/medlineplus/geneticbraindisorders.html Huntington's Disease http://www.nlm.nih.gov/medlineplus/huntingtonsdisease.html Laser Eye Surgery http://www.nlm.nih.gov/medlineplus/lasereyesurgery.html Leukodystrophies http://www.nlm.nih.gov/medlineplus/leukodystrophies.html Muscle Disorders http://www.nlm.nih.gov/medlineplus/muscledisorders.html Muscular Dystrophy http://www.nlm.nih.gov/medlineplus/musculardystrophy.html Neuromuscular Disorders http://www.nlm.nih.gov/medlineplus/neuromusculardisorders.html Spinal Muscular Atrophy http://www.nlm.nih.gov/medlineplus/spinalmuscularatrophy.html Tourette Syndrome http://www.nlm.nih.gov/medlineplus/tourettesyndrome.html
Within the health topic page dedicated to muscular dystrophy, the following was listed: •
Diagnosis/Symptoms Accurate and Affordable Diagnosis of Duchenne Muscular Dystrophy Source: National Institute of Neurological Disorders and Stroke http://www.ninds.nih.gov/news_and_events/news_article_dmd_test.htm 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 Muscle Biopsies Source: Muscular Dystrophy Association http://www.mdausa.org/publications/Quest/q74ss.html
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Treatment Treatment for Duchenne MD: Braces and Wheelchairs Source: Parent Project for Muscular Dystrophy Research http://www.parentprojectmd.org/aboutdmd/treatment/braces.html Treatment for Duchenne MD: Physical Therapy Source: Parent Project for Muscular Dystrophy Research http://www.parentprojectmd.org/aboutdmd/treatment/physical.html Treatment for Duchenne MD: Seating Requirements Source: Parent Project for Muscular Dystrophy Research http://www.parentprojectmd.org/aboutdmd/treatment/seating_req.html Treatment for Duchenne MD: Steroids/Nutritional Supplements/Antibiotics Source: Parent Project for Muscular Dystrophy Research http://www.parentprojectmd.org/aboutdmd/treatment/supplements.html Treatment for Duchenne MD: Surgery for Scoliosis Source: Parent Project for Muscular Dystrophy Research http://www.parentprojectmd.org/aboutdmd/treatment/surgery.html
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Coping 101 Hints to “Help-with-Ease” for Patients with Neuromuscular Disease Source: Muscular Dystrophy Association http://www.mdausa.org/publications/101hints/ Learning to Live with Neuromuscular Disease: A Message for Parents Source: Muscular Dystrophy Association http://www.mdausa.org/publications/learning/index.html Parents & Family: Connecting with Your Son Who Has Duchenne MD Source: Parent Project for Muscular Dystrophy Research http://www.parentprojectmd.org/people/family/connecting.html Parents & Family: Daily Life with Duchenne MD Source: Parent Project for Muscular Dystrophy Research http://www.parentprojectmd.org/people/family/life.html
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Specific Conditions/Aspects Facts about Duchenne and Becker Muscular Dystrophies (DMD and BMD) Source: Muscular Dystrophy Association http://www.mdausa.org/publications/fa-dmdbmd-what.html Facts about Facioscapulohumeral Muscular Dystrophy Source: Muscular Dystrophy Association http://www.mdausa.org/publications/fa-fshd.html Facts about Limb-Girdle Muscular Dystrophy (LGMD) Source: Muscular Dystrophy Association http://www.mdausa.org/publications/fa-lgmd-qa.html Facts about Myotonic Muscular Dystrophy Source: Muscular Dystrophy Association http://www.mdausa.org/publications/fa-mmd-qa.html
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Facts about Rare Muscular Dystrophies: Congenital, Distal, Emery-Dreifuss and Oculopharyngeal Muscular Dystrophies Source: Muscular Dystrophy Association http://www.mdausa.org/publications/fa-rareMD.html Lambert-Eaton Myasthenic Syndrome http://www.ninds.nih.gov/health_and_medical/disorders/lambert-eaton.htm Treating Scoliosis in Muscular Dystrophy Source: Virtual Hospital http://www.vh.org/pediatric/patient/orthopaedics/scoliosisandmd/index.html •
Children Breathe Easy: Respiratory Care for Children with Muscular Dystrophy Source: Muscular Dystrophy Association http://www.mdausa.org/publications/breathe/index.html Everybody's Different Nobody's Perfect Source: Muscular Dystrophy Association http://www.mdausa.org/publications/nobody/index.html
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From the National Institutes of Health Muscular Dystrophy (MD) http://www.ninds.nih.gov/health_and_medical/disorders/md.htm
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Organizations Muscular Dystrophy Association http://www.mdausa.org/ National Institute of Arthritis and Musculoskeletal and Skin Diseases http://www.niams.nih.gov/ National Institute of Neurological Disorders and Stroke http://www.ninds.nih.gov/ Parent Project for Muscular Dystrophy Research http://www.parentprojectmd.org/
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Research Faulty Muscle Repair Implicated in Muscular Dystrophies Source: National Institute of Neurological Disorders and Stroke http://www.ninds.nih.gov/news_and_events/news_article_md_repair.htm MDA Research Advances Rapidly Source: Muscular Dystrophy Association http://www.mdausa.org/publications/resdev.html Muscle Stem Cells Show Promise against Muscular Dystrophy in Mouse Model Source: National Institute of Arthritis and Musculoskeletal and Skin Diseases http://www.nih.gov/news/pr/jul2002/niams-03.htm
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Muscular Dystrophy Mouse Model Yields Potential Growth Factor Treatment Source: National Institute of Arthritis and Musculoskeletal and Skin Diseases http://www.nih.gov/news/pr/may2002/niams-22.htm Scientists Identify a New Kind of Genetic Problem in Muscular Dystrophy Source: National Institute of Neurological Disorders and Stroke http://www.nih.gov/news/pr/aug2002/ninds-08.htm •
Teenagers Making Sense of Muscular Dystrophy Source: Nemours Foundation http://kidshealth.org/teen/diseases_conditions/bones/muscular_dystrophy.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 muscular dystrophy. 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: •
FSHD [Facioscapulohumeral Muscular Dystrophy] Source: Lexington, MA: FSH Society, Inc. 1997. 12 p. Contact: Available from FSH Society, Inc. Administrative Office, 3 Westwood Road, Lexington, MA 02420. (781) 860-0501. Fax (781) 860-0599. Web Site: fshsociety.org. PRICE: Single copy free. Summary: This brochure for people with facioscapulohumeral muscular dystrophy (FSHD) uses a question and answer format to provide information on the cause, symptoms, prognosis, and treatment of this autosomal dominant inherited disease. The estimated occurrence of FSHD is one in 20,000. Most people who have FSHD inherited a chromosome 4 genetic mutation from a parent with the disease. FSHD is characterized by progressive weakening and loss of skeletal muscle. Symptoms are usually first seen in the face, shoulders, and upper arms. Muscles in the neck, torso, and lower limbs eventually weaken also. People with the disease typically begin to notice muscle weakness during adolescence, and a physician can usually recognize and diagnose the disease by the age of 20. An infantile form of FSHD may occur in rare instances. Prognosis is variable, and there is no treatment or cure for FSHD, physical, occupational, and nutrition therapy may be beneficial. Surgery to attach the scapulae to the back may
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be performed in some cases. The brochure also provides information on the FSH Society. 1 figure.
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: •
FAQ - About Loving Paws Dogs Summary: Loving Paws Dogs are service dogs trained for disabled children (specifically muscular dystrophy, cerebral palsy and spina bifida) up to aged 18. This information answers questions about the program. Source: Loving Paws Assistance Dogs http://www.healthfinder.gov/scripts/recordpass.asp?RecordType=0&RecordID=4239
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Muscular Dystrophy Summary: Muscular dystrophy (MD) refers to a group of genetic diseases characterized by progressive weakness and degeneration of the skeletal or voluntary muscles which control movement. Source: National Institute of Neurological Disorders and Stroke, National Institutes of Health http://www.healthfinder.gov/scripts/recordpass.asp?RecordType=0&RecordID=749 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 muscular dystrophy. The drawbacks of this approach are that the information is not organized by theme and that the references are often a mix of information for professionals and patients. Nevertheless, a large number of the listed Web sites provide useful background information. We can only recommend this route, therefore, for relatively rare or specific disorders, or when using highly targeted searches. To use the NIH search utility, visit the following Web page: http://search.nih.gov/index.html. Additional Web Sources
A number of Web sites are available to the public that often link to government sites. These can also point you in the direction of essential information. The following is a representative sample: •
AOL: http://search.aol.com/cat.adp?id=168&layer=&from=subcats
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Family Village: http://www.familyvillage.wisc.edu/specific.htm
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Google: http://directory.google.com/Top/Health/Conditions_and_Diseases/
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Med Help International: http://www.medhelp.org/HealthTopics/A.html
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Open Directory Project: http://dmoz.org/Health/Conditions_and_Diseases/
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Yahoo.com: http://dir.yahoo.com/Health/Diseases_and_Conditions/
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WebMDHealth: http://my.webmd.com/health_topics
Associations and Muscular Dystrophy The following is a list of associations that provide information on and resources relating to muscular dystrophy: •
Challenge Air For Kids and Friends Telephone: (214) 351-3353 Fax: (214) 351-4565 Email:
[email protected] Web Site: http://www.challengeair.com Background: Challenge Air for Kids and Friends is a national nonprofit organization dedicated to providing motivational, occupational, recreational, and educational therapy to disabled, disadvantaged, and seriously ill children through the experience of flight with a disabled pilot free of charge. Challenge Air was established in 1993 by a pilot who lost the use of his legs when his plane crashed while returning from a combat mission over Vietnam. The purpose of the flights is to provide enjoyable experiences and to demonstrate that the human spirit can prevail over any physical or mental obstacle. Challenge Air organizes day long events that allow groups of children to enjoy motivational flights, food, and other fun. Events have include handicapped athletic groups, therapy programs, social service organizations, and more. A typical Challenge Air fly day serves more than 150 children and their families. Each program is underwritten by individual, corporate, and philanthropic donations. Challenge Air has flown over 4,000 children in 15 states as well as Canada. Challenge Air has several materials available including brochures, pamphlets, videos, and a newsletter. Relevant area(s) of interest: Muscular Dystrophy
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Disabled Sports USA Telephone: (301) 217-0960 Fax: (301) 217-0968 Email:
[email protected] Web Site: http://www.dsusa.org/~dsusa/dsusa.html Background: Disabled Sports USA (DS/USA) is a not-for-profit organization dedicated to ensuring that disabled people have access to sports, recreation, and physical education programs from preschool through college to elite sports levels. Established in 1967 by disabled Vietnam veterans, DS/USA serves people with physical disabilities that restrict mobility, including amputations, weakness or paralysis of both legs (paraplegia), paralysis of all four limbs (quadriplegia), cerebral palsy, head injury, multiple sclerosis, muscular dystrophy, spina bifida, stroke, and visual impairment. DS/USA consists of more than 60,000 members and 80 chapters around the United
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States. Educational materials include a general information packet, a newsletter entitled 'Disabled Sports USA Update,' and a sports magazine entitled 'Challenge.' Program activities include sporting activities and events, patient education (e.g., workshops), and patient networking. •
European Alliance of Muscular Dystrophy Associations Telephone: 44 171 720 8055 Fax: 44 171 498 8963 Email:
[email protected] Web Site: http://www.sonnet.co.uk/eamda/ Background: The European Alliance of Muscular Dystrophy Associations (EAMDA) is a nonprofit organization that was established in 1971. The organization consists of delegates from its over 30 member associations and primarily serves as an information network, providing advice about neuromuscular conditions and offering information, support, and resources to families, caregivers, and professionals throughout Europe. Muscular dystrophy refers to a group of genetic disorders characterized by progressive degeneration of muscle fibers, resulting in associated weakness, disability, and deformity. The different forms of muscular dystrophy may be categorized based upon age at onset, specific muscle groups affected, rate of disease progression, and mode of inheritance. Forms of muscular dystrophy include Becker muscular dystrophy, Duchenne muscular dystrophy, and ocular myopathies. The EAMDA includes a Youth Organization, known as the EYO, that is made up of delegates who represent the young people in their own national associations. The EYO is committed to providing assistance and support for young people with muscular dystrophy; promoting networking among affected youths, encouraging the exchange of information and mutual support; and providing assistance to the National Youth Organizations concerning the different aspects of these disorders, such as quality of life issues, self image, and medical intervention. The EAMDA also offers a variety of educational materials including fact sheets on the different forms of muscular dystrophy, a regular newsletter, and several additional publications. The EAMDA's web site on the Internet provides information on the Alliance and its Youth Organization; access to MD fact sheets, the EAMDA newsletter, and a glossary of MD-related terms; contact information for neuromuscular disorder support groups; and links to additional sources of information and support.
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Facio-Scapulo-Humeral Society, Inc Telephone: (781) 860-0501 Fax: (781) 860-0599 Email:
[email protected] Web Site: http://www.fshsociety.org Background: Facio-Scapulo-Humeral Society, Inc. (FSH Society) is a voluntary not-forprofit organization created to address issues and needs specifically related to FacioScapulo-Humeral Muscular Dystrophy (FSHD), a rare inherited neuromuscular disorder. Established in 1989, the Facio-Scapulo-Humeral Society is dedicated to encouraging and promoting ongoing scientific and clinical research and development into the nature of Facio-Scapulo-Humeral Syndrome through solicitation of grants and contributions from private foundations, the pharmaceutical industry, and others. The Society also seeks to develop educational programs aimed at the medical community,
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government bodies, and the public. The Society accumulates and disseminates timely information about FSHD and actively cooperates with related organizations to foster communication among all interested parties. In addition, Facio-Scapulo-Humeral Society promotes professional education; provides appropriate referrals including to support groups; and promotes patient advocacy and legislation beneficial to individuals with FSHD. The Society offers a variety of educational and support materials including brochures, fact sheets, and a newsletter. The FSH Society provies grants for research on FSHD. •
Gazette International Networking Institute (GINI) Telephone: (314) 534-0475 Fax: (314) 534-5070 Email:
[email protected] Web Site: http://www.post-polio.org Background: The Gazette International Networking Institute (GINI) is a voluntary notfor-profit organization dedicated to supporting the independent living, self-direction, dignity, and personal achievement of people with disabilities. Established in 1960, GINI is a primary source of information about independent living, polio and its late effects, home mechanical ventilation, and ventilation equipment. In addition to compiling and disseminating information, GINI enables people to network with one another to exchange information, resources, and support. The organization also conducts advocacy efforts related to poliomyelitis and late effects of poliomyelitis through its coordination of International Polio Network. GINI has expanded its role to assist additional ventilation users through International Ventilator Users Network. GINI also conducts conferences and workshops; provides directories listing appropriate clinics, health care professionals, and support groups; and publishes a listing of sources for oral and nasal face masks. GINI offers a variety of additional educational and support materials including handbooks, regular newsletters, pamphlets, brochures, and proceedings from its conferences.
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International Myotonic Dystrophy Organization, Inc. (IMDO) Telephone: (818) 951-2311 Toll-free: (866) 679-7954 Fax: (818) 352-0096 Email:
[email protected] and
[email protected] Web Site: http://www.myotonicdystrophy.org Background: The International Myotonic Dystrophy Organization, Inc., (IMDO) functions on an international basis, supporting patients with information and services worldwide. The organization assists patients and their families with their problems via the toll-free helpline and/or e-mail and mail. IMDO has a very informative website, publishes a monthly e-newsletter, offers Medical Alert cards and some educational materials,and facilitates support groups as well as Pen Pals via e-mail. The organization provides referrals and reference information to the public and professionals, promotes collaborative research and disseminates research information. The International Myotonic Dystrophy Organization is a National 501 (c) tax-exempt organization.
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March of Dimes Birth Defects Foundation Telephone: (914) 428-7100 Toll-free: (888) 663-4637 Fax: (914) 997-4763 Email:
[email protected] Web Site: http://www.marchofdimes.com Background: The March of Dimes Birth Defects Foundation is a national not-for-profit organization that was established in 1938. The mission of the Foundation is to improve the health of babies by preventing birth defects and infant mortality. The March of Dimes funds programs of research, community services, education, and advocacy. Educational programs that seek to prevent birth defects are important to the Foundation and to that end it also produces a wide variety of printed informational materials and videos. The Pregnancy and Newborn Health Education Center staffs trained health information specialists who provide researched information on pregnancy issues, complications and risks, newborn care, birth defects, genetic diseases and related topics as well as referrals to relevant organizations and support groups.
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Muscular Dystrophy Association Telephone: (520) 529-2000 Toll-free: (800) 572-1717 Fax: (520) 529-5300 Email:
[email protected] Web Site: http://www.mdausa.org Background: Established in 1950, the Muscular Dystrophy Association (MDA) is a nonprofit, voluntary health agency dedicated to providing comprehensive medical services to individuals affected by over 40 neuromuscular diseases. MDA provides these services at some 230 hospital-affiliated clinics across the United States. The Association's worldwide research program allocates more than $28 million a year, seeking cures and treatments for neuromuscular disorders. MDA funds some 400 individual scientific investigations each year at a cost of $57 a minute, around the clock. This represents the largest single initiative to advance current knowledge of neuromuscular diseases and to find cures and treatments for this group of diseases. Relevant area(s) of interest: Muscular Dystrophy, Myotonic Dystrophy
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Muscular Dystrophy Association (Australia) Telephone: 61 3 9320 9555 Toll-free: 1 800 656 632 Fax: 61 3 9320 9595 Email:
[email protected] Web Site: http://www.mda.org.au Background: The Muscular Dystrophy Association (MDA) is a not-for-profit organization in Australia that was founded in the early 1970s by a group of people affected by muscular dystrophy (MD). Muscular dystrophy refers to a group of genetic disorders characterized by progressive degeneration of muscle fibers, resulting in associated weakness, disability, and deformity. The different forms of muscular dystrophy may be categorized based upon age at onset, specific muscle groups affected, rate of disease progression, and mode of inheritance. The Muscular Dystrophy Association is committed to improving the quality of life of individuals with muscular
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dystrophy and other neuromuscular diseases. To fulfill its mission and objectives, the Association provides a variety of educational materials, conducts MDA camps for children and adults with neuromuscular disorders, and promotes and supports research. The Association's materials include information sheets on different forms of muscular dystrophy, parents guides, glossaries, and materials discussing the various aspects of these disorders. The Association also maintains a web site on the Internet that provides understandable information on muscular dystrophy, a FAQ ('frequently asked questions') area, a guestbook area for online visitors, and links to additional sources of information and support. In 1985, the Association established the Muscular Dystrophy Research Foundation to help ensure sufficient funding to accelerate research and to provide funds required for treatment programs. The MDA, in association with St. Vincents Hospital and the Department of Medicine, Melbourne University, is also affiliated with the Melbourne Neuromuscular Research Centre, and sponsors scientific research seminars and conferences. Relevant area(s) of interest: Muscular Dystrophy, Myotonic Dystrophy •
Muscular Dystrophy Association of Canada Telephone: 416-488-0030 Toll-free: (800) 567-2873 Fax: 416-488-7523 Email:
[email protected] Web Site: http://www.mdac.ca Background: The Muscular Dystrophy Association of Canada (MDAC) is not-for-profit voluntary organization dedicated to eliminating neuromuscular disorders and alleviating the associated symptoms. Neuromuscular disorders are a group of diseases affecting the body s ability to move due to an underlying neurological disease. Whether the problem originates within the motor nerve cell, the nerve, or the muscle, the most commonly experienced symptoms are varying degrees of progressive muscle weakness and wasting. There are over 40 nerve and muscle disorders covered under the umbrella of the Muscular Dystrophy Association of Canada. Founded in 1954, the Association s three main goals are funding research that will ultimately result in discovering the causes, treatments, and cures for muscular dystrophy and other neuromuscular disorders; providing support services that assist individuals and families affected by neuromuscular disorders; and providing information to affected individuals, their families, health care professionals, educators, and the general public as to the nature and management of neuromuscular disorders. Services provided by MDAC include the dissemination of information, advocacy, referrals, travel assistance, and some financial assistance with mobility equipment. MDAC also houses donated equipment for use by clients upon request. Informational brochures include 'What Is Spinal Muscular Atrophy?,' 'What Is Myotonic Dystrophy?,' and 'What Is Muscular Dystrophy?'. MDAC also publishes a news magazine entitled 'CONNECTIONS'. Additionally, the organization provides advocacy services in resolving individual or community problems. Relevant area(s) of interest: Muscular Dystrophy
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Muscular Dystrophy Group of Great Britain and Northern Ireland Telephone: 0171 720 8055 Fax: 0171 498 0670 Email:
[email protected]
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Web Site: http://www.sonnet.co.uk/muscular-dystrophy Background: The Muscular Dystrophy Group of Great Britain and Northern Ireland (MDG) is a voluntary research organization dedicated to identifying the causes of muscular dystrophy and allied conditions in order to develop treatments that will alleviate symptoms while working to discover a cure. Muscular Dystrophy (MD) is a group of rare inherited muscle wasting diseases. In some forms of MD, muscles of the hips and shoulders are weakened, walking abnormalities (ataxia) develop, and mild mental retardation may be present. MDG was established in 1959 and is affiliated with two other organizations, the European Alliance of MDA and the World Alliance of MDA. The MDG currently provides funding for seven Muscle Centers that are designed to provide comprehensive medical care to individuals with neuromuscular conditions, and to provide researchers within and between the Centers with medical data and samples that will assist research. There are two types of MDG grants to centers, a Research Servicing Grant which supports costs such as equipment servicing, specialist technicians, secretarial staff, etc. and a Medical Services Grant which provides computing facilities and secretarial staff. Educational materials include an annual review covering different areas of concern for people affected by Muscular Dystrophy. Relevant area(s) of interest: Muscular Dystrophy •
Muscular Dystrophy Ireland Telephone: 353 1 8721501 Fax: 353 1 8724482 Email:
[email protected] Web Site: http://www.mdi.ie/ Background: Muscular Dystrophy Ireland (MDI) is a national voluntary nonprofit organization with a membership of over 500 individuals and families throughout Ireland. The organization's primary objective is to provide support to people with muscular dystrophy and their families through the provision of a range of services, including family support, information, respite services, holidays, youth activities, transport, and independent living and training opportunities. Muscular dystrophy is a collective term referring to a variety of genetic neuromuscular disorders characterized by progressive degeneration and weakening of muscles. The different forms of muscular dystrophy may be categorized based upon age at onset, specific muscle groups affected, rate of disease progression, the genetic mutation and mode of inheritance. Muscular Dystrophy Ireland was founded in 1972 and currently has a network of offices throughout Ireland. In addition to providing supportive services, MDI is committed to promoting and supporting research, conducting annual general meetings, organizing special youth activities for its younger members, and offering a variety of educational materials including the 'MDI News Update.' Muscular Dystrophy Ireland also maintains a web site on the Internet that discusses the organization's mission, objectives, and services; information about muscular dystrophy; and provides linkage to additional sources of information and support.
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Parent Project Muscular Dystrophy Telephone: (513) 424-0696 Toll-free: (800) 714-5437 Fax: (513) 425-9907 Email:
[email protected]
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Web Site: http://www.parentprojectmd.org Background: Parent Project Muscular Dystrophy (formerly the Parent Project for Duchenne Muscular Dystrophy) is a not-for-profit national health organization founded in 1994 by parents of children with Duchenne and Becker Muscular Dystrophy. Today, its work focuses in five areas: It identifies, funds, and disseminates informaiton about promising Duchenne and Becker Muscular Dystrophy research and its applications. It seeks to ensure that all families, caregivers, health care professionals and others have access to current information about treatment and care options for children with Duchenne and Becker MD. It seeks to ensure that health and human services policymakers afford the same priority to Duchenne and Becker MD as to other disorders of similar incidence and prevalence. It seeks to ensure that the voices of people with and affected by these diseases are heard, and it seeks collaboration with other international organizations addressing these diseases. Relevant area(s) of interest: Muscular Dystrophy •
Prader-Willi Syndrome Association (UK) Telephone: 01 332 365676 Fax: 01 332 360401 Email:
[email protected] Web Site: http://www.pwsa.co.uk Background: The Prader Willi Syndrome Association (UK)(PWSA (UK)) is a voluntary organization located in the United Kingdom and dedicated to promoting the care, welfare, treatment, interests, education, and advancement of persons affected by Prader Willi Syndrome. These goals are achieved by contacting and supporting families concerned with the disorder; raising funds; inviting and receiving contributions by way of subscriptions and donations; establishing mutual self-help groups; and fostering and supporting ongoing research. Prader Willi Syndrome is a complex multisystem disorder characterized by muscular weakness during infancy (infantile hypotonia); failure to thrive; a decrease in the efficiency of the testes or ovaries (hypogonadism); short stature and impaired intellectual and behavioral functioning. Eating excessive amounts of food (hyperphagia) leads to severe obesity in early childhood and adolescence. Established in 1981, PWSA consists of 1,200 members, including people with PWS, parents and professionals from health, social services and education. The Association produces various educational materials including a quarterly magazine and brochures. In addition, the Association, conducts regular support group meetings and supports ongoing patient advocacy.
•
Scapuloperoneal Disease Association Telephone: (908) 269-0357 Toll-free: TTY: Fax: (908) 269-0357 Background: The Scapuloperoneal Disease Association (SPDA) is an international selfhelp and research organization dedicated to providing information, assistance, and support to individuals and family members affected by Scapuloperoneal Muscular Dystrophy. Scapuloperoneal Muscular Dystrophy, a rare inherited muscular dystrophy that may become apparent early in life, is characterized by slowly progressive muscle weakness of the upper arms and shoulder blade area (scapula) as well as certain leg muscle groups below the knee (peroneal). Established in 1994, the SPDA provides
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networking services that enable affected individuals and family members to exchange information, support and resources; promotes basic and clinical research development; fosters communication among related organizations; serves to represent individuals and family members affected by Scapuloperoneal Muscular Dystrophy; and accumulates and disseminates information and materials concerning this disorder. •
Shriners Hospitals for Children Telephone: (813) 281-0300 Toll-free: (800) 237-5055 Fax: (813) 281-8496 Web Site: http://www.shrinershq.org Background: The Shriners Hospital for Children and the Shriners Burn Institutes are a network of pediatric hospitals that provide no-cost medical care to children with orthopedic problems or burn injuries. Shriners Hospital conducts research on orthopedic treatment and burn care and trains healthcare professionals in the treatment of orthopedic disabilities and burn injuries. Established in 1922, the hospitals are substantially funded through the Shriners Hospital for Children endowment fund. The hospitals treat children with a variety of diseases including (but not limited to) scoliosis, osteogenesis imperfecta, Legg Calve Perthes, and others. Burns and spinal injuries are also treated. Shriners Hospital consists of 23 chapters and offers educational materials such as 'Between Us' magazine, '20 Questions,' and 'The Story of Shriners Hospitals.' In addition, the organization assists in training physicians and other medical professionals in the treatment of orthopedic disabilities and burn injuries. Relevant area(s) of interest: Muscular Dystrophy
•
Society for Muscular Dystrophy Information International Telephone: (902) 685-3961 Fax: (902) 685-3962 Email:
[email protected] Web Site: None Background: The Society for Muscular Dystrophy Information International (SMDI) is a not-for-profit registered Canadian charity dedicated to assisting people in helping themselves by reducing the national and international isolation of individuals and organizations concerned with neuromuscular disorders/disabilities (e.g., muscular dystrophy and over 50 allied disorders). In general, 'neuromuscular disorder' is a term used to describe a group of over 50 diseases affecting the body s motor neurons (nerves and muscles). Symptoms may include varying degrees of progressive muscle weakness and loss of muscle mass (wasting). SMDI was established in 1983 to provide a nontechnical information link for individuals with neuromuscular disorders and for organizations around the world; to link people with other people and organizations concerned with their disorder; to share information to assist people in helping themselves; and to create increased public awareness of this group of disorders. The Society publishes two bi-annual newsletters entitled 'SMDI International Newsletter,' a publication for those concerned with muscular dystrophy or the allied disorders and 'Access - Able Information,' a quarterly disability information resource publication. In addition to educational materials, brochures and referrals are available. Relevant area(s) of interest: Muscular Dystrophy
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•
The Arc (a national organization on mental retardation) Telephone: (301) 565-3842 Toll-free: (800) 433-5255 Fax: (301) 565-3843 Email:
[email protected] Web Site: http://thearc.org/ Background: The Arc is the largest organization in the United States that is solely devoted to improving the lives of all children and adults with mental retardation. The organization offers support to families affected by mental retardation and fosters research and educational programs on the prevention of mental retardation. The Arc is committed to securing opportunities for all people with mental retardation. To this end, the organization emphasizes personal opportunities for choice in education, housing, employment, and entertainment. The Arc is further committed to reducing the incidence and limiting the consequences of mental retardation through research, advocacy, and mutual support. The Arc provides leadership in the field of mental retardation and develops necessary human and financial resources to attain its goals. In addition, the Arc provides a wide variety of educational materials for parents, teachers, health care professionals, and others, including a regular newsletter, handbooks, instruction packets, reports, booklets, audio-visual aids, posters, and brochures. Many materials are available in Spanish.
•
United Ostomy Association, Inc Telephone: (949) 660-8624 Toll-free: (800) 826-0826 Fax: (949) 660-9262 Email:
[email protected] Web Site: http://www.uoa.org Background: Established in 1962, the United Ostomy Association, Inc. is a volunteerbased nonprofit health organization dedicated to providing education, information, support and advocacy for people who have had or will have intestinal or urinary diversion. The Association, which has approximately 25,000 members and 450 chapters nationwide, offers networking programs, distributes educational materials, provides referrals to other resources, and conducts a yearly national conference. The Association also operates a camp for children between the ages of 11 and 17 who have had ostomy surgery or have bowel or bladder concerns. The United Ostomy Association produces educational materials including a quarterly magazine, patient care guides, and a website. Special services are provided to networks of teens, young adults, thirty-plus, parents of children with ostomies, gay and lesbian ostomates and individuals with continent diversions.
Finding Associations There are several Internet directories that provide lists of medical associations with information on or resources relating to muscular dystrophy. By consulting all of associations listed in this chapter, you will have nearly exhausted all sources for patient associations concerned with muscular dystrophy.
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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 muscular dystrophy. 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 “muscular dystrophy” (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 “muscular dystrophy”. 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 “muscular dystrophy” (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 “muscular dystrophy” (or a synonym) into the search box, and click “Submit Query.”
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APPENDIX C. FINDING MEDICAL LIBRARIES Overview In this Appendix, we show you how to quickly find a medical library in your area.
Preparation Your local public library and medical libraries have interlibrary loan programs with the National Library of Medicine (NLM), one of the largest medical collections in the world. According to the NLM, most of the literature in the general and historical collections of the National Library of Medicine is available on interlibrary loan to any library. If you would like to access NLM medical literature, then visit a library in your area that can request the publications for you.26
Finding a Local Medical Library The quickest method to locate medical libraries is to use the Internet-based directory published by the National Network of Libraries of Medicine (NN/LM). This network includes 4626 members and affiliates that provide many services to librarians, health professionals, and the public. To find a library in your area, simply visit http://nnlm.gov/members/adv.html or call 1-800-338-7657.
Medical Libraries in the U.S. and Canada In addition to the NN/LM, the National Library of Medicine (NLM) lists a number of libraries with reference facilities that are open to the public. The following is the NLM’s list and includes hyperlinks to each library’s Web site. These Web pages can provide information on hours of operation and other restrictions. The list below is a small sample of
26
Adapted from the NLM: http://www.nlm.nih.gov/psd/cas/interlibrary.html.
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libraries recommended by the National Library of Medicine (sorted alphabetically by name of the U.S. state or Canadian province where the library is located)27: •
Alabama: Health InfoNet of Jefferson County (Jefferson County Library Cooperative, Lister Hill Library of the Health Sciences), http://www.uab.edu/infonet/
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Alabama: Richard M. Scrushy Library (American Sports Medicine Institute)
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Arizona: Samaritan Regional Medical Center: The Learning Center (Samaritan Health System, Phoenix, Arizona), http://www.samaritan.edu/library/bannerlibs.htm
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California: Kris Kelly Health Information Center (St. Joseph Health System, Humboldt), http://www.humboldt1.com/~kkhic/index.html
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California: Community Health Library of Los Gatos, http://www.healthlib.org/orgresources.html
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California: Consumer Health Program and Services (CHIPS) (County of Los Angeles Public Library, Los Angeles County Harbor-UCLA Medical Center Library) - Carson, CA, http://www.colapublib.org/services/chips.html
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California: Gateway Health Library (Sutter Gould Medical Foundation)
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California: Health Library (Stanford University Medical Center), http://wwwmed.stanford.edu/healthlibrary/
•
California: Patient Education Resource Center - Health Information and Resources (University of California, San Francisco), http://sfghdean.ucsf.edu/barnett/PERC/default.asp
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California: Redwood Health Library (Petaluma Health Care District), http://www.phcd.org/rdwdlib.html
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California: Los Gatos PlaneTree Health Library, http://planetreesanjose.org/
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California: Sutter Resource Library (Sutter Hospitals Foundation, Sacramento), http://suttermedicalcenter.org/library/
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California: Health Sciences Libraries (University of California, Davis), http://www.lib.ucdavis.edu/healthsci/
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California: ValleyCare Health Library & Ryan Comer Cancer Resource Center (ValleyCare Health System, Pleasanton), http://gaelnet.stmarysca.edu/other.libs/gbal/east/vchl.html
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California: Washington Community Health Resource Library (Fremont), http://www.healthlibrary.org/
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Colorado: William V. Gervasini Memorial Library (Exempla Healthcare), http://www.saintjosephdenver.org/yourhealth/libraries/
•
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.
Finding Medical Libraries 351
•
Connecticut: Waterbury Hospital Health Center Library (Waterbury Hospital, Waterbury), http://www.waterburyhospital.com/library/consumer.shtml
•
Delaware: Consumer Health Library (Christiana Care Health System, Eugene du Pont Preventive Medicine & Rehabilitation Institute, Wilmington), http://www.christianacare.org/health_guide/health_guide_pmri_health_info.cfm
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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/
•
Idaho: DeArmond Consumer Health Library (Kootenai Medical Center, Coeur d’Alene), http://www.nicon.org/DeArmond/index.htm
•
Illinois: Health Learning Center of Northwestern Memorial Hospital (Chicago), http://www.nmh.org/health_info/hlc.html
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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/
•
Louisiana: Louisiana State University Health Sciences Center Medical LibraryShreveport, http://lib-sh.lsuhsc.edu/
•
Maine: Franklin Memorial Hospital Medical Library (Franklin Memorial Hospital, Farmington), http://www.fchn.org/fmh/lib.htm
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Maine: Gerrish-True Health Sciences Library (Central Maine Medical Center, Lewiston), http://www.cmmc.org/library/library.html
•
Maine: Hadley Parrot Health Science Library (Eastern Maine Healthcare, Bangor), http://www.emh.org/hll/hpl/guide.htm
•
Maine: Maine Medical Center Library (Maine Medical Center, Portland), http://www.mmc.org/library/
•
Maine: Parkview Hospital (Brunswick), http://www.parkviewhospital.org/
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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
•
Maine: Stephens Memorial Hospital’s Health Information Library (Western Maine Health, Norway), http://www.wmhcc.org/Library/
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•
Manitoba, Canada: Consumer & Patient Health Information Service (University of Manitoba Libraries), http://www.umanitoba.ca/libraries/units/health/reference/chis.html
•
Manitoba, Canada: J.W. Crane Memorial Library (Deer Lodge Centre, Winnipeg), http://www.deerlodge.mb.ca/crane_library/about.asp
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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
•
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
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Massachusetts: UMass HealthNet (University of Massachusetts Medical School, Worchester), http://healthnet.umassmed.edu/
•
Michigan: Botsford General Hospital Library - Consumer Health (Botsford General Hospital, Library & Internet Services), http://www.botsfordlibrary.org/consumer.htm
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Michigan: Helen DeRoy Medical Library (Providence Hospital and Medical Centers), http://www.providence-hospital.org/library/
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Michigan: Marquette General Hospital - Consumer Health Library (Marquette General Hospital, Health Information Center), http://www.mgh.org/center.html
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Michigan: Patient Education Resouce Center - University of Michigan Cancer Center (University of Michigan Comprehensive Cancer Center, Ann Arbor), http://www.cancer.med.umich.edu/learn/leares.htm
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Michigan: Sladen Library & Center for Health Information Resources - Consumer Health Information (Detroit), http://www.henryford.com/body.cfm?id=39330
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Montana: Center for Health Information (St. Patrick Hospital and Health Sciences Center, Missoula)
•
National: Consumer Health Library Directory (Medical Library Association, Consumer and Patient Health Information Section), http://caphis.mlanet.org/directory/index.html
•
National: National Network of Libraries of Medicine (National Library of Medicine) provides library services for health professionals in the United States who do not have access to a medical library, http://nnlm.gov/
•
National: NN/LM List of Libraries Serving the Public (National Network of Libraries of Medicine), http://nnlm.gov/members/
Finding Medical Libraries 353
•
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
•
Oregon: Planetree Health Resource Center (Mid-Columbia Medical Center, The Dalles), http://www.mcmc.net/phrc/
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Pennsylvania: Community Health Information Library (Milton S. Hershey Medical Center, Hershey), http://www.hmc.psu.edu/commhealth/
•
Pennsylvania: Community Health Resource Library (Geisinger Medical Center, Danville), http://www.geisinger.edu/education/commlib.shtml
•
Pennsylvania: HealthInfo Library (Moses Taylor Hospital, Scranton), http://www.mth.org/healthwellness.html
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Pennsylvania: Hopwood Library (University of Pittsburgh, Health Sciences Library System, Pittsburgh), http://www.hsls.pitt.edu/guides/chi/hopwood/index_html
•
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/
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•
South Dakota: Rapid City Regional Hospital Medical Library (Rapid City Regional Hospital), http://www.rcrh.org/Services/Library/Default.asp
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Texas: Houston HealthWays (Houston Academy of Medicine-Texas Medical Center Library), http://hhw.library.tmc.edu/
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Washington: Community Health Library (Kittitas Valley Community Hospital), http://www.kvch.com/
•
Washington: Southwest Washington Medical Center Library (Southwest Washington Medical Center, Vancouver), http://www.swmedicalcenter.com/body.cfm?id=72
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ONLINE GLOSSARIES The Internet provides access to a number of free-to-use medical dictionaries. The National Library of Medicine has compiled the following list of online dictionaries: •
ADAM Medical Encyclopedia (A.D.A.M., Inc.), comprehensive medical reference: http://www.nlm.nih.gov/medlineplus/encyclopedia.html
•
MedicineNet.com Medical Dictionary (MedicineNet, Inc.): http://www.medterms.com/Script/Main/hp.asp
•
Merriam-Webster Medical Dictionary (Inteli-Health, Inc.): http://www.intelihealth.com/IH/
•
Multilingual Glossary of Technical and Popular Medical Terms in Eight European Languages (European Commission) - Danish, Dutch, English, French, German, Italian, Portuguese, and Spanish: http://allserv.rug.ac.be/~rvdstich/eugloss/welcome.html
•
On-line Medical Dictionary (CancerWEB): http://cancerweb.ncl.ac.uk/omd/
•
Rare Diseases Terms (Office of Rare Diseases): http://ord.aspensys.com/asp/diseases/diseases.asp
•
Technology Glossary (National Library of Medicine) - Health Care Technology: http://www.nlm.nih.gov/nichsr/ta101/ta10108.htm
Beyond these, MEDLINEplus contains a very patient-friendly encyclopedia covering every aspect of medicine (licensed from A.D.A.M., Inc.). The ADAM Medical Encyclopedia can be accessed at http://www.nlm.nih.gov/medlineplus/encyclopedia.html. ADAM is also available on commercial Web sites such as drkoop.com (http://www.drkoop.com/) and Web MD (http://my.webmd.com/adam/asset/adam_disease_articles/a_to_z/a). The NIH suggests the following Web sites in the ADAM Medical Encyclopedia when searching for information on muscular dystrophy: •
Basic Guidelines for Muscular Dystrophy Muscular dystrophy Web site: http://www.nlm.nih.gov/medlineplus/ency/article/001190.htm Muscular dystrophy - resources Web site: http://www.nlm.nih.gov/medlineplus/ency/article/002154.htm
•
Signs & Symptoms for Muscular Dystrophy Drooling Web site: http://www.nlm.nih.gov/medlineplus/ency/article/003048.htm Eyelid drooping Web site: http://www.nlm.nih.gov/medlineplus/ency/article/003035.htm Hearing loss Web site: http://www.nlm.nih.gov/medlineplus/ency/article/003044.htm
356 Muscular Dystrophy
Hyperthermia Web site: http://www.nlm.nih.gov/medlineplus/ency/article/003090.htm Hypotonia Web site: http://www.nlm.nih.gov/medlineplus/ency/article/003298.htm Lordosis Web site: http://www.nlm.nih.gov/medlineplus/ency/article/003278.htm Muscle contractures Web site: http://www.nlm.nih.gov/medlineplus/ency/article/003193.htm Muscle weakness Web site: http://www.nlm.nih.gov/medlineplus/ency/article/003174.htm Problems walking Web site: http://www.nlm.nih.gov/medlineplus/ency/article/003199.htm Wasting Web site: http://www.nlm.nih.gov/medlineplus/ency/article/003188.htm Weakness Web site: http://www.nlm.nih.gov/medlineplus/ency/article/003174.htm •
Diagnostics and Tests for Muscular Dystrophy Aldolase Web site: http://www.nlm.nih.gov/medlineplus/ency/article/003566.htm ALT Web site: http://www.nlm.nih.gov/medlineplus/ency/article/003473.htm ANA Web site: http://www.nlm.nih.gov/medlineplus/ency/article/003535.htm AST Web site: http://www.nlm.nih.gov/medlineplus/ency/article/003472.htm Biopsy Web site: http://www.nlm.nih.gov/medlineplus/ency/article/003416.htm Chorionic villus sampling Web site: http://www.nlm.nih.gov/medlineplus/ency/article/003406.htm CPK Web site: http://www.nlm.nih.gov/medlineplus/ency/article/003503.htm CPK isoenzymes Web site: http://www.nlm.nih.gov/medlineplus/ency/article/003504.htm
Online Glossaries 357
Creatine kinase Web site: http://www.nlm.nih.gov/medlineplus/ency/article/003503.htm Creatinine Web site: http://www.nlm.nih.gov/medlineplus/ency/article/003475.htm Creatinine - urine Web site: http://www.nlm.nih.gov/medlineplus/ency/article/003610.htm Differential Web site: http://www.nlm.nih.gov/medlineplus/ency/article/003657.htm ECG Web site: http://www.nlm.nih.gov/medlineplus/ency/article/003868.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 FSH Web site: http://www.nlm.nih.gov/medlineplus/ency/article/003710.htm LDH Web site: http://www.nlm.nih.gov/medlineplus/ency/article/003471.htm LDH isoenzymes Web site: http://www.nlm.nih.gov/medlineplus/ency/article/003499.htm MRI Web site: http://www.nlm.nih.gov/medlineplus/ency/article/003335.htm Muscle biopsy Web site: http://www.nlm.nih.gov/medlineplus/ency/article/003924.htm Myoglobin - serum Web site: http://www.nlm.nih.gov/medlineplus/ency/article/003663.htm Myoglobin - urine Web site: http://www.nlm.nih.gov/medlineplus/ency/article/003664.htm Serum CPK Web site: http://www.nlm.nih.gov/medlineplus/ency/article/003503.htm •
Background Topics for Muscular Dystrophy Gene Web site: http://www.nlm.nih.gov/medlineplus/ency/article/002371.htm
358 Muscular Dystrophy
Genes Web site: http://www.nlm.nih.gov/medlineplus/ency/article/002371.htm Genetic counseling Web site: http://www.nlm.nih.gov/medlineplus/ency/article/002053.htm Inheritance Web site: http://www.nlm.nih.gov/medlineplus/ency/article/002048.htm Muscular dystrophy - support group Web site: http://www.nlm.nih.gov/medlineplus/ency/article/002154.htm Prenatal diagnosis Web site: http://www.nlm.nih.gov/medlineplus/ency/article/002053.htm Proximal Web site: http://www.nlm.nih.gov/medlineplus/ency/article/002287.htm Respiratory Web site: http://www.nlm.nih.gov/medlineplus/ency/article/002290.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
•
MEL-Michigan Electronic Library List of Online Health and Medical Dictionaries (Michigan Electronic Library): http://mel.lib.mi.us/health/health-dictionaries.html
•
Patient Education: Glossaries (DMOZ Open Directory Project): http://dmoz.org/Health/Education/Patient_Education/Glossaries/
•
Web of Online Dictionaries (Bucknell University): http://www.yourdictionary.com/diction5.html#medicine
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MUSCULAR DYSTROPHY DICTIONARY The definitions below are derived from official public sources, including the National Institutes of Health [NIH] and the European Union [EU]. 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] Aberrant: Wandering or deviating from the usual or normal course. [EU] Ablate: In surgery, is to remove. [NIH] Acantholysis: Separation of the prickle cells of the stratum spinosum of the epidermis, resulting in atrophy of the prickle cell layer. It is seen in diseases such as pemphigus vulgaris (see pemphigus) and keratosis follicularis. [NIH] Acceptor: A substance which, while normally not oxidized by oxygen or reduced by hydrogen, can be oxidized or reduced in presence of a substance which is itself undergoing oxidation or reduction. [NIH] 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] Acetylglucosamine: The N-acetyl derivative of glucosamine. [NIH] Acidity: The quality of being acid or sour; containing acid (hydrogen ions). [EU] 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] Activities of Daily Living: The performance of the basic activities of self care, such as dressing, ambulation, eating, etc., in rehabilitation. [NIH] Actomyosin: A protein complex of actin and myosin occurring in muscle. It is the essential contractile substance of muscle. [NIH] Acuity: Clarity or clearness, especially of the vision. [EU] Acyl: Chemical signal used by bacteria to communicate. [NIH] Adaptability: Ability to develop some form of tolerance to conditions extremely different from those under which a living organism evolved. [NIH] Adaptation: 1. The adjustment of an organism to its environment, or the process by which it enhances such fitness. 2. The normal ability of the eye to adjust itself to variations in the intensity of light; the adjustment to such variations. 3. The decline in the frequency of firing of a neuron, particularly of a receptor, under conditions of constant stimulation. 4. In dentistry, (a) the proper fitting of a denture, (b) the degree of proximity and interlocking of restorative material to a tooth preparation, (c) the exact adjustment of bands to teeth. 5. In
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microbiology, the adjustment of bacterial physiology to a new environment. [EU] Adenosine: A nucleoside that is composed of adenine and d-ribose. Adenosine or adenosine derivatives play many important biological roles in addition to being components of DNA and RNA. Adenosine itself is a neurotransmitter. [NIH] Adenovirus: A group of viruses that cause respiratory tract and eye infections. Adenoviruses used in gene therapy are altered to carry a specific tumor-fighting gene. [NIH] Adipose Tissue: Connective tissue composed of fat cells lodged in the meshes of areolar tissue. [NIH] Adjunctive Therapy: Another treatment used together with the primary treatment. Its purpose is to assist the primary treatment. [NIH] Adjustment: The dynamic process wherein the thoughts, feelings, behavior, and biophysiological mechanisms of the individual continually change to adjust to the environment. [NIH] Adolescence: The period of life beginning with the appearance of secondary sex characteristics and terminating with the cessation of somatic growth. The years usually referred to as adolescence lie between 13 and 18 years of age. [NIH] Adrenergic: Activated by, characteristic of, or secreting epinephrine or substances with similar activity; the term is applied to those nerve fibres that liberate norepinephrine at a synapse when a nerve impulse passes, i.e., the sympathetic fibres. [EU] Adverse Effect: An unwanted side effect of treatment. [NIH] Aerobic: In biochemistry, reactions that need oxygen to happen or happen when oxygen is present. [NIH] Aetiology: Study of the causes of disease. [EU] Afferent: Concerned with the transmission of neural impulse toward the central part of the nervous system. [NIH] Affinity: 1. Inherent likeness or relationship. 2. A special attraction for a specific element, organ, or structure. 3. Chemical affinity; the force that binds atoms in molecules; the tendency of substances to combine by chemical reaction. 4. The strength of noncovalent chemical binding between two substances as measured by the dissociation constant of the complex. 5. In immunology, a thermodynamic expression of the strength of interaction between a single antigen-binding site and a single antigenic determinant (and thus of the stereochemical compatibility between them), most accurately applied to interactions among simple, uniform antigenic determinants such as haptens. Expressed as the association constant (K litres mole -1), which, owing to the heterogeneity of affinities in a population of antibody molecules of a given specificity, actually represents an average value (mean intrinsic association constant). 6. The reciprocal of the dissociation constant. [EU] Affinity Chromatography: In affinity chromatography, a ligand attached to a column binds specifically to the molecule to be purified. [NIH] Age Groups: Persons classified by age from birth (infant, newborn) to octogenarians and older (aged, 80 and over). [NIH] Aged, 80 and Over: A person 80 years of age and older. [NIH] Ageing: A physiological or morphological change in the life of an organism or its parts, generally irreversible and typically associated with a decline in growth and reproductive vigor. [NIH] 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
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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] Air Sacs: Thin-walled sacs or spaces which function as a part of the respiratory system in birds, fishes, insects, and mammals. [NIH] Airway: A device for securing unobstructed passage of air into and out of the lungs during general anesthesia. [NIH] Airway Resistance: Physiologically, the opposition to flow of air caused by the forces of friction. As a part of pulmonary function testing, it is the ratio of driving pressure to the rate of air flow. [NIH] Albuterol: A racemic mixture with a 1:1 ratio of the r-isomer, levalbuterol, and s-albuterol. It is a short-acting beta 2-adrenergic agonist with its main clinical use in asthma. [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] Alkaline Phosphatase: An enzyme that catalyzes the conversion of an orthophosphoric monoester and water to an alcohol and orthophosphate. EC 3.1.3.1. [NIH] Alkaloid: A member of a large group of chemicals that are made by plants and have nitrogen in them. Some alkaloids have been shown to work against cancer. [NIH] Alleles: Mutually exclusive forms of the same gene, occupying the same locus on homologous chromosomes, and governing the same biochemical and developmental process. [NIH] Allogeneic: Taken from different individuals of the same species. [NIH] Alpha-helix: One of the secondary element of protein. [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] Alveoli: Tiny air sacs at the end of the bronchioles in the lungs. [NIH] Ameliorating: A changeable condition which prevents the consequence of a failure or accident from becoming as bad as it otherwise would. [NIH] Amine: An organic compound containing nitrogen; any member of a group of chemical compounds formed from ammonia by replacement of one or more of the hydrogen atoms by organic (hydrocarbon) radicals. The amines are distinguished as primary, secondary, and tertiary, according to whether one, two, or three hydrogen atoms are replaced. The amines include allylamine, amylamine, ethylamine, methylamine, phenylamine, propylamine, and many other compounds. [EU] Amino acid: Any organic compound containing an amino (-NH2 and a carboxyl (- COOH)
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group. The 20 a-amino acids listed in the accompanying table are the amino acids from which proteins are synthesized by formation of peptide bonds during ribosomal translation of messenger RNA; all except glycine, which is not optically active, have the L configuration. Other amino acids occurring in proteins, such as hydroxyproline in collagen, are formed by posttranslational enzymatic modification of amino acids residues in polypeptide chains. There are also several important amino acids, such as the neurotransmitter y-aminobutyric acid, that have no relation to proteins. Abbreviated AA. [EU] Amino Acid Sequence: The order of amino acids as they occur in a polypeptide chain. This is referred to as the primary structure of proteins. It is of fundamental importance in determining protein conformation. [NIH] Amino 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] Ammonia: A colorless alkaline gas. It is formed in the body during decomposition of organic materials during a large number of metabolically important reactions. [NIH] Amplification: The production of additional copies of a chromosomal DNA sequence, found as either intrachromosomal or extrachromosomal DNA. [NIH] Amygdala: Almond-shaped group of basal nuclei anterior to the inferior horn of the lateral ventricle of the brain, within the temporal lobe. The amygdala is part of the limbic system. [NIH]
Amyotrophy: A type of diabetic neuropathy that causes muscle weakness and wasting. [NIH] Anabolic: Relating to, characterized by, or promoting anabolism. [EU] Anaesthesia: Loss of feeling or sensation. Although the term is used for loss of tactile sensibility, or of any of the other senses, it is applied especially to loss of the sensation of pain, as it is induced to permit performance of surgery or other painful procedures. [EU] Anal: Having to do with the anus, which is the posterior opening of the large bowel. [NIH] 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] Androgenic: Producing masculine characteristics. [EU] Anemia: A reduction in the number of circulating erythrocytes or in the quantity of hemoglobin. [NIH] Anesthesia: A state characterized by loss of feeling or sensation. This depression of nerve function is usually the result of pharmacologic action and is induced to allow performance of surgery or other painful procedures. [NIH] Anesthetics: Agents that are capable of inducing a total or partial loss of sensation, especially tactile sensation and pain. They may act to induce general anesthesia, in which an unconscious state is achieved, or may act locally to induce numbness or lack of sensation at a targeted site. [NIH]
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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] 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] Ankle: That part of the lower limb directly above the foot. [NIH] Ankyrin Repeat: Protein motif that contains a 33-amino acid long sequence that often occurs in tandem arrays. This repeating sequence of 33-amino acids was discovered in ankyrin where it is involved in interaction with the anion exchanger (band 3 protein). Ankyrin repeats cooperatively fold into structures that mediate molecular recognition via proteinprotein interactions. [NIH] Annealing: The spontaneous alignment of two single DNA strands to form a double helix. [NIH]
Anomalies: Birth defects; abnormalities. [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] Antibacterial: A substance that destroys bacteria or suppresses their growth or reproduction. [EU] Antibiotic: A drug used to treat infections caused by bacteria and other microorganisms. [NIH]
Antibodies: Immunoglobulin molecules having a specific amino acid sequence by virtue of which they interact only with the antigen that induced their synthesis in cells of the lymphoid series (especially plasma cells), or with an antigen closely related to it. [NIH] Antibody: A type of protein made by certain white blood cells in response to a foreign substance (antigen). Each antibody can bind to only a specific antigen. The purpose of this binding is to help destroy the antigen. Antibodies can work in several ways, depending on the nature of the antigen. Some antibodies destroy antigens directly. Others make it easier for white blood cells to destroy the antigen. [NIH] Anticoagulant: A drug that helps prevent blood clots from forming. Also called a blood thinner. [NIH] Antigen: Any substance which is capable, under appropriate conditions, of inducing a specific immune response and of reacting with the products of that response, that is, with specific antibody or specifically sensitized T-lymphocytes, or both. Antigens may be soluble substances, such as toxins and foreign proteins, or particulate, such as bacteria and tissue cells; however, only the portion of the protein or polysaccharide molecule known as the antigenic determinant (q.v.) combines with antibody or a specific receptor on a lymphocyte. Abbreviated Ag. [EU] Antigen-Antibody Complex: The complex formed by the binding of antigen and antibody molecules. The deposition of large antigen-antibody complexes leading to tissue damage causes immune complex diseases. [NIH] Anti-infective: An agent that so acts. [EU] Anti-inflammatory: Having to do with reducing inflammation. [NIH] Antioxidant: A substance that prevents damage caused by free radicals. Free radicals are highly reactive chemicals that often contain oxygen. They are produced when molecules are
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split to give products that have unpaired electrons. This process is called oxidation. [NIH] 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] Anus: The opening of the rectum to the outside of the body. [NIH] Anxiety: Persistent feeling of dread, apprehension, and impending disaster. [NIH] Aorta: The main trunk of the systemic arteries. [NIH] Apamin: A highly neurotoxic polypeptide from the venom of the honey bee (Apis mellifera). It consists of 18 amino acids with two disulfide bridges and causes hyperexcitability resulting in convulsions and respiratory paralysis. [NIH] Apoptosis: One of the two mechanisms by which cell death occurs (the other being the pathological process of necrosis). Apoptosis is the mechanism responsible for the physiological deletion of cells and appears to be intrinsically programmed. It is characterized by distinctive morphologic changes in the nucleus and cytoplasm, chromatin cleavage at regularly spaced sites, and the endonucleolytic cleavage of genomic DNA (DNA fragmentation) at internucleosomal sites. This mode of cell death serves as a balance to mitosis in regulating the size of animal tissues and in mediating pathologic processes associated with tumor growth. [NIH] Applicability: A list of the commodities to which the candidate method can be applied as presented or with minor modifications. [NIH] Aptitude: The ability to acquire general or special types of knowledge or skill. [NIH] Aqueous: Having to do with water. [NIH] Arginine: An essential amino acid that is physiologically active in the L-form. [NIH] Arterial: Pertaining to an artery or to the arteries. [EU] Arteries: The vessels carrying blood away from the heart. [NIH] Arterioles: The smallest divisions of the arteries located between the muscular arteries and the capillaries. [NIH] Artery: Vessel-carrying blood from the heart to various parts of the body. [NIH] Articular: Of or pertaining to a joint. [EU] Ascending Colon: The part of the colon on the right side of the abdomen. [NIH] Aseptic: Free from infection or septic material; sterile. [EU] Assay: Determination of the amount of a particular constituent of a mixture, or of the biological or pharmacological potency of a drug. [EU] Astrocytes: The largest and most numerous neuroglial cells in the brain and spinal cord. Astrocytes (from "star" cells) are irregularly shaped with many long processes, including those with "end feet" which form the glial (limiting) membrane and directly and indirectly contribute to the blood brain barrier. They regulate the extracellular ionic and chemical environment, and "reactive astrocytes" (along with microglia) respond to injury. Astrocytes have high- affinity transmitter uptake systems, voltage-dependent and transmitter-gated ion channels, and can release transmitter, but their role in signaling (as in many other functions) is not well understood. [NIH] Asymptomatic: Having no signs or symptoms of disease. [NIH] Ataxia: Impairment of the ability to perform smoothly coordinated voluntary movements.
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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] Atracurium: A non-depolarizing neuromuscular blocking agent with short duration of action. Its lack of significant cardiovascular effects and its lack of dependence on good kidney function for elimination provide clinical advantage over alternate non-depolarizing neuromuscular blocking agents. [NIH] Atresia: Lack of a normal opening from the esophagus, intestines, or anus. [NIH] Atrial: Pertaining to an atrium. [EU] Atrial Fibrillation: Disorder of cardiac rhythm characterized by rapid, irregular atrial impulses and ineffective atrial contractions. [NIH] Atrioventricular: Pertaining to an atrium of the heart and to a ventricle. [EU] Atrium: A chamber; used in anatomical nomenclature to designate a chamber affording entrance to another structure or organ. Usually used alone to designate an atrium of the heart. [EU] Atrophy: Decrease in the size of a cell, tissue, organ, or multiple organs, associated with a variety of pathological conditions such as abnormal cellular changes, ischemia, malnutrition, or hormonal changes. [NIH] Atropine: A toxic alkaloid, originally from Atropa belladonna, but found in other plants, mainly Solanaceae. [NIH] Atypical: Irregular; not conformable to the type; in microbiology, applied specifically to strains of unusual type. [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] Autologous: Taken from an individual's own tissues, cells, or DNA. [NIH] Autonomic: Self-controlling; functionally independent. [EU] Autonomic Nervous System: The enteric, parasympathetic, and sympathetic nervous systems taken together. Generally speaking, the autonomic nervous system regulates the internal environment during both peaceful activity and physical or emotional stress. Autonomic activity is controlled and integrated by the central nervous system, especially the hypothalamus and the solitary nucleus, which receive information relayed from visceral afferents; these and related central and sensory structures are sometimes (but not here) considered to be part of the autonomic nervous system itself. [NIH] 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] Axillary: Pertaining to the armpit area, including the lymph nodes that are located there. [NIH]
Axonal: Condition associated with metabolic derangement of the entire neuron and is manifest by degeneration of the distal portion of the nerve fiber. [NIH]
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Axons: Nerve fibers that are capable of rapidly conducting impulses away from the neuron cell body. [NIH] Bacteria: Unicellular prokaryotic microorganisms which generally possess rigid cell walls, multiply by cell division, and exhibit three principal forms: round or coccal, rodlike or bacillary, and spiral or spirochetal. [NIH] Bacterial Infections: Infections by bacteria, general or unspecified. [NIH] Bacterial Physiology: Physiological processes and activities of 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] Band 3 Protein: A ubiquitous membrane transport protein found in the plasma membrane of diverse cell types and tissues, and in nuclear, mitochondrial, and Golgi membranes. It is the major integral transmembrane protein of the erythrocyte membrane, comprising 25% of the total membrane protein and occurring at 1 million copies per cell. It exists as a dimer and provides a channel for the transport of anions across the membrane. [NIH] Baroreflex: A negative feedback system which buffers short-term changes in blood pressure. Increased pressure stretches blood vessels which activates pressoreceptors (baroreceptors) in the vessel walls. The net response of the central nervous system is a reduction of central sympathetic outflow. This reduces blood pressure both by decreasing peripheral vascular resistance and by lowering cardiac output. Because the baroreceptors are tonically active, the baroreflex can compensate rapidly for both increases and decreases in blood pressure. [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] Base Sequence: The sequence of purines and pyrimidines in nucleic acids and polynucleotides. It is also called nucleotide or nucleoside sequence. [NIH] 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] 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]
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Bifida: A defect in development of the vertebral column in which there is a central deficiency of the vertebral lamina. [NIH] Bilateral: Affecting both the right and left side of body. [NIH] Bile: An emulsifying agent produced in the liver and secreted into the duodenum. Its composition includes bile acids and salts, cholesterol, and electrolytes. It aids digestion of fats in the duodenum. [NIH] Binding Sites: The reactive parts of a macromolecule that directly participate in its specific combination with another molecule. [NIH] Biochemical: Relating to biochemistry; characterized by, produced by, or involving chemical reactions in living organisms. [EU] Bioengineering: The application of engineering principles to the solution of biological problems, for example, remote-handling devices, life-support systems, controls, and displays. [NIH] Biogenesis: The origin of life. It includes studies of the potential basis for life in organic compounds but excludes studies of the development of altered forms of life through mutation and natural selection, which is evolution. [NIH] Biological 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] Bioluminescence: The emission of light by living organisms such as the firefly, certain mollusks, beetles, fish, bacteria, fungi and protozoa. [NIH] Biopsy: Removal and pathologic examination of specimens in the form of small pieces of tissue from the living body. [NIH] Biopsy specimen: Tissue removed from the body and examined under a microscope to determine whether disease is present. [NIH] Biotechnology: Body of knowledge related to the use of organisms, cells or cell-derived constituents for the purpose of developing products which are technically, scientifically and clinically useful. Alteration of biologic function at the molecular level (i.e., genetic engineering) is a central focus; laboratory methods used include transfection and cloning technologies, sequence and structure analysis algorithms, computer databases, and gene and protein structure function analysis and prediction. [NIH] Bladder: The organ that stores urine. [NIH] 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] 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 Coagulation: The process of the interaction of blood coagulation factors that results in an insoluble fibrin clot. [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,
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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] Blot: To transfer DNA, RNA, or proteins to an immobilizing matrix such as nitrocellulose. [NIH]
Body Composition: The relative amounts of various components in the body, such as percent body fat. [NIH] Body Fluids: Liquid components of living organisms. [NIH] Bone Density: The amount of mineral per square centimeter of bone. This is the definition used in clinical practice. Actual bone density would be expressed in grams per milliliter. It is most frequently measured by photon absorptiometry or x-ray computed tomography. [NIH] Bone Marrow: The soft tissue filling the cavities of bones. Bone marrow exists in two types, yellow and red. Yellow marrow is found in the large cavities of large bones and consists mostly of fat cells and a few primitive blood cells. Red marrow is a hematopoietic tissue and is the site of production of erythrocytes and granular leukocytes. Bone marrow is made up of a framework of connective tissue containing branching fibers with the frame being filled with marrow cells. [NIH] Bone Marrow Transplantation: The transference of bone marrow from one human or animal to another. [NIH] Bone scan: A technique to create images of bones on a computer screen or on film. A small amount of radioactive material is injected into a blood vessel and travels through the bloodstream; it collects in the bones and is detected by a scanner. [NIH] 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] Brachial: All the nerves from the arm are ripped from the spinal cord. [NIH] Brachytherapy: A collective term for interstitial, intracavity, and surface radiotherapy. It uses small sealed or partly-sealed sources that may be placed on or near the body surface or within a natural body cavity or implanted directly into the tissues. [NIH] Bradykinin: A nonapeptide messenger that is enzymatically produced from kallidin in the blood where it is a potent but short-lived agent of arteriolar dilation and increased capillary permeability. Bradykinin is also released from mast cells during asthma attacks, from gut walls as a gastrointestinal vasodilator, from damaged tissues as a pain signal, and may be a neurotransmitter. [NIH] Brain Diseases: Pathologic conditions affecting the brain, which is composed of the 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 Stem: The part of the brain that connects the cerebral hemispheres with the spinal cord. It consists of the mesencephalon, pons, and medulla oblongata. [NIH] Branch: Most commonly used for branches of nerves, but applied also to other structures. [NIH]
Breakdown: A physical, metal, or nervous collapse. [NIH]
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Breeding: The science or art of changing the constitution of a population of plants or animals through sexual reproduction. [NIH] Bronchial: Pertaining to one or more bronchi. [EU] Bronchioles: The tiny branches of air tubes in the lungs. [NIH] Bronchopulmonary: Pertaining to the lungs and their air passages; both bronchial and pulmonary. [EU] Bronchopulmonary Dysplasia: A chronic lung disease appearing in certain newborn infants treated for respiratory distress syndrome with mechanical ventilation and elevated concentration of inspired oxygen. [NIH] Buffers: A chemical system that functions to control the levels of specific ions in solution. When the level of hydrogen ion in solution is controlled the system is called a pH buffer. [NIH]
Bulbar: Pertaining to a bulb; pertaining to or involving the medulla oblongata, as bulbar paralysis. [EU] Cachexia: General ill health, malnutrition, and weight loss, usually associated with chronic disease. [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-Binding Proteins: Proteins to which calcium ions are bound. They can act as transport proteins, regulator proteins or activator proteins. [NIH] Calculi: An abnormal concretion occurring mostly in the urinary and biliary tracts, usually composed of mineral salts. Also called stones. [NIH] Callus: A callosity or hard, thick skin; the bone-like reparative substance that is formed round the edges and fragments of broken bone. [NIH] Calmodulin: A heat-stable, low-molecular-weight activator protein found mainly in the brain and heart. The binding of calcium ions to this protein allows this protein to bind to cyclic nucleotide phosphodiesterases and to adenyl cyclase with subsequent activation. Thereby this protein modulates cyclic AMP and cyclic GMP levels. [NIH] Calpain: Cysteine proteinase found in many tissues. Hydrolyzes a variety of endogenous proteins including neuropeptides, cytoskeletal proteins, proteins from smooth muscle, cardiac muscle, liver, platelets and erythrocytes. Two subclasses having high and low calcium sensitivity are known. Removes Z-discs and M-lines from myofibrils. Activates phosphorylase kinase and cyclic nucleotide-independent protein kinase. [NIH] Camping: Living outdoors as a recreational activity. [NIH] Capital Financing: Institutional funding for facilities and for equipment which becomes a part of the assets of the institution. [NIH] Capsid: The outer protein protective shell of a virus, which protects the viral nucleic acid. [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]
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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] Carcinogens: Substances that increase the risk of neoplasms in humans or animals. Both genotoxic chemicals, which affect DNA directly, and nongenotoxic chemicals, which induce neoplasms by other mechanism, are included. [NIH] Carcinoma: Cancer that begins in the skin or in tissues that line or cover internal organs. [NIH]
Cardiac: Having to do with the heart. [NIH] Cardiac arrest: A sudden stop of heart function. [NIH] Cardiac Output: The volume of blood passing through the heart per unit of time. It is usually expressed as liters (volume) per minute so as not to be confused with stroke volume (volume per beat). [NIH] Cardiomyopathy: A general diagnostic term designating primary myocardial disease, often of obscure or unknown etiology. [EU] Cardiovascular: Having to do with the heart and blood vessels. [NIH] Cardiovascular disease: Any abnormal condition characterized by dysfunction of the heart and blood vessels. CVD includes atherosclerosis (especially coronary heart disease, which can lead to heart attacks), cerebrovascular disease (e.g., stroke), and hypertension (high blood pressure). [NIH] Carnitine: Constituent of striated muscle and liver. It is used therapeutically to stimulate gastric and pancreatic secretions and in the treatment of hyperlipoproteinemias. [NIH] Carotene: The general name for a group of pigments found in green, yellow, and leafy vegetables, and yellow fruits. The pigments are fat-soluble, unsaturated aliphatic hydrocarbons functioning as provitamins and are converted to vitamin A through enzymatic processes in the intestinal wall. [NIH] Case report: A detailed report of the diagnosis, treatment, and follow-up of an individual patient. Case reports also contain some demographic information about the patient (for example, age, gender, ethnic origin). [NIH] Case series: A group or series of case reports involving patients who were given similar treatment. Reports of case series usually contain detailed information about the individual patients. This includes demographic information (for example, age, gender, ethnic origin) and information on diagnosis, treatment, response to treatment, and follow-up after treatment. [NIH] Caspase: Enzyme released by the cell at a crucial stage in apoptosis in order to shred all cellular proteins. [NIH] Catabolism: Any destructive metabolic process by which organisms convert substances into excreted compounds. [EU] Cataract: An opacity, partial or complete, of one or both eyes, on or in the lens or capsule, especially an opacity impairing vision or causing blindness. The many kinds of cataract are classified by their morphology (size, shape, location) or etiology (cause and time of occurrence). [EU] Catheter: A flexible tube used to deliver fluids into or withdraw fluids from the body. [NIH] Catheterization: Use or insertion of a tubular device into a duct, blood vessel, hollow organ, or body cavity for injecting or withdrawing fluids for diagnostic or therapeutic purposes. It differs from intubation in that the tube here is used to restore or maintain patency in
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obstructions. [NIH] Caudal: Denoting a position more toward the cauda, or tail, than some specified point of reference; same as inferior, in human anatomy. [EU] Causal: Pertaining to a cause; directed against a cause. [EU] Caveolae: Endocytic/exocytic cell membrane structures rich in glycosphingolipids, cholesterol, and lipid-anchored membrane proteins that function in endocytosis (potocytosis), transcytosis, and signal transduction. Caveolae assume various shapes from open pits to closed vesicles. Caveolar coats are composed of caveolins. [NIH] Caveolins: The main structural proteins of caveolae. Several distinct genes for caveolins have been identified. [NIH] Cell: The individual unit that makes up all of the tissues of the body. All living things are made up of one or more cells. [NIH] Cell Adhesion: Adherence of cells to surfaces or to other cells. [NIH] Cell Adhesion Molecules: Surface ligands, usually glycoproteins, that mediate cell-to-cell adhesion. Their functions include the assembly and interconnection of various vertebrate systems, as well as maintenance of tissue integration, wound healing, morphogenic movements, cellular migrations, and metastasis. [NIH] Cell Communication: Any of several ways in which living cells of an organism communicate with one another, whether by direct contact between cells or by means of chemical signals carried by neurotransmitter substances, hormones, and cyclic AMP. [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 Fusion: Fusion of somatic cells in vitro or in vivo, which results in somatic cell hybridization. [NIH] Cell membrane: Cell membrane = plasma membrane. The structure enveloping a cell, enclosing the cytoplasm, and forming a selective permeability barrier; it consists of lipids, proteins, and some carbohydrates, the lipids thought to form a bilayer in which integral proteins are embedded to varying degrees. [EU] Cell Membrane Structures: Structures which are part of the cell membrane or have cell membrane as a major part of their structure. [NIH] Cell motility: The ability of a cell to move. [NIH] Cell Polarity: Orientation of intracellular structures especially with respect to the apical and basolateral domains of the plasma membrane. Polarized cells must direct proteins from the Golgi apparatus to the appropriate domain since tight junctions prevent proteins from diffusing between the two domains. [NIH] Cell proliferation: An increase in the number of cells as a result of cell growth and cell division. [NIH] Cell Respiration: The metabolic process of all living cells (animal and plant) in which oxygen is used to provide a source of energy for the cell. [NIH] Cell 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]
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Cell Transplantation: Transference of cells within an individual, between individuals of the same species, or between individuals of different species. [NIH] Central Nervous System: The main information-processing organs of the nervous system, consisting of the brain, spinal cord, and meninges. [NIH] Cerebellar: Pertaining to the cerebellum. [EU] Cerebellum: Part of the metencephalon that lies in the posterior cranial fossa behind the brain stem. It is concerned with the coordination of movement. [NIH] Cerebral: Of or pertaining of the cerebrum or the brain. [EU] Cerebral Cortex: The thin layer of gray matter on the surface of the cerebral hemisphere that develops from the telencephalon and folds into gyri. It reaches its highest development in man and is responsible for intellectual faculties and higher mental functions. [NIH] Cerebral 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] Cerebrovascular: Pertaining to the blood vessels of the cerebrum, or brain. [EU] Cerebrum: The largest part of the brain. It is divided into two hemispheres, or halves, called the cerebral hemispheres. The cerebrum controls muscle functions of the body and also controls speech, emotions, reading, writing, and learning. [NIH] Cervical: Relating to the neck, or to the neck of any organ or structure. Cervical lymph nodes are located in the neck; cervical cancer refers to cancer of the uterine cervix, which is the lower, narrow end (the "neck") of the uterus. [NIH] Cervix: The lower, narrow end of the uterus that forms a canal between the uterus and vagina. [NIH] Chaperonins: A class of sequence-related molecular chaperones found in bacteria, mitochondria, and plastids. Chaperonins are abundant constitutive proteins that increase in amount after stresses such as heat shock, bacterial infection of macrophages, and an increase in the cellular content of unfolded proteins. Bacterial chaperonins are major immunogens in human bacterial infections because of their accumulation during the stress of infection. Two members of this class of chaperones are chaperonin 10 and chaperonin 60. [NIH] Character: In current usage, approximately equivalent to personality. The sum of the relatively fixed personality traits and habitual modes of response of an individual. [NIH] 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 wall: The ribs and muscles, bones, and joints that make up the area of the body between the neck and the abdomen. [NIH] Chiasma: An anatomy term for an X-shaped crossing (for example, of nerves or tendons.)
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[NIH]
Chimeric Proteins: Proteins in individuals that are derived from genetically different zygotes. [NIH] Chin: The anatomical frontal portion of the mandible, also known as the mentum, that contains the line of fusion of the two separate halves of the mandible (symphysis menti). This line of fusion divides inferiorly to enclose a triangular area called the mental protuberance. On each side, inferior to the second premolar tooth, is the mental foramen for the passage of blood vessels and a nerve. [NIH] 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] Chondrocytes: Polymorphic cells that form cartilage. [NIH] Choroid: The thin, highly vascular membrane covering most of the posterior of the eye between the retina and sclera. [NIH] Chromatin: The material of chromosomes. It is a complex of DNA, histones, and nonhistone proteins (chromosomal proteins, non-histone) found within the nucleus of a cell. [NIH] Chromosomal: Pertaining to chromosomes. [EU] Chromosome: Part of a cell that contains genetic information. Except for sperm and eggs, all human cells contain 46 chromosomes. [NIH] Chromosome Fragility: Susceptibility of chromosomes to breakage and translocation or other aberrations. Chromosome fragile sites are regions that show up in karyotypes as a gap (uncondensed stretch) on the chromatid arm. They are associated with chromosome break sites and other aberrations. A fragile site on the X chromosome is associated with fragile X syndrome. Fragile sites are designated by the letters "FRA" followed by the designation for the specific chromosome and a letter which refers to the different fragile sites on a chromosome (e.g. FRAXA). [NIH] Chronic: A disease or condition that persists or progresses over a long period of time. [NIH] Chronic Disease: Disease or ailment of long duration. [NIH] Chronic renal: Slow and progressive loss of kidney function over several years, often resulting in end-stage renal disease. People with end-stage renal disease need dialysis or transplantation to replace the work of the kidneys. [NIH] Cirrhosis: A type of chronic, progressive liver disease. [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] Clear cell carcinoma: A rare type of tumor of the female genital tract in which the inside of the cells looks clear when viewed under a microscope. [NIH] Cleft Palate: Congenital fissure of the soft and/or hard palate, due to faulty fusion. [NIH] Clinical Medicine: The study and practice of medicine by direct examination of the patient. [NIH]
Clinical study: A research study in which patients receive treatment in a clinic or other
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medical facility. Reports of clinical studies can contain results for single patients (case reports) or many patients (case series or clinical trials). [NIH] Clinical trial: A research study that tests how well new medical treatments or other interventions work in people. Each study is designed to test new methods of screening, prevention, diagnosis, or treatment of a disease. [NIH] Clone: The term "clone" has acquired a new meaning. It is applied specifically to the bits of inserted foreign DNA in the hybrid molecules of the population. Each inserted segment originally resided in the DNA of a complex genome amid millions of other DNA segment. [NIH]
Cloning: The production of a number of genetically identical individuals; in genetic engineering, a process for the efficient replication of a great number of identical DNA molecules. [NIH] Cod Liver Oil: Oil obtained from fresh livers of the cod family, Gadidae. It is a source of vitamins A and D. [NIH] Codon: A set of three nucleotides in a protein coding sequence that specifies individual amino acids or a termination signal (codon, terminator). Most codons are universal, but some organisms do not produce the transfer RNAs (RNA, transfer) complementary to all codons. These codons are referred to as unassigned codons (codons, nonsense). [NIH] Coenzyme: An organic nonprotein molecule, frequently a phosphorylated derivative of a water-soluble vitamin, that binds with the protein molecule (apoenzyme) to form the active enzyme (holoenzyme). [EU] Cofactor: A substance, microorganism or environmental factor that activates or enhances the action of another entity such as a disease-causing agent. [NIH] Cognition: Intellectual or mental process whereby an organism becomes aware of or obtains knowledge. [NIH] Colchicine: A major alkaloid from Colchicum autumnale L. and found also in other Colchicum species. Its primary therapeutic use is in the treatment of gout, but it has been used also in the therapy of familial Mediterranean fever (periodic disease). [NIH] 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] Colon: The long, coiled, tubelike organ that removes water from digested food. The remaining material, solid waste called stool, moves through the colon to the rectum and leaves the body through the anus. [NIH] Combinatorial: A cut-and-paste process that churns out thousands of potentially valuable compounds at once. [NIH] Complement: A term originally used to refer to the heat-labile factor in serum that causes immune cytolysis, the lysis of antibody-coated cells, and now referring to the entire functionally related system comprising at least 20 distinct serum proteins that is the effector
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not only of immune cytolysis but also of other biologic functions. Complement activation occurs by two different sequences, the classic and alternative pathways. The proteins of the classic pathway are termed 'components of complement' and are designated by the symbols C1 through C9. C1 is a calcium-dependent complex of three distinct proteins C1q, C1r and C1s. The proteins of the alternative pathway (collectively referred to as the properdin system) and complement regulatory proteins are known by semisystematic or trivial names. Fragments resulting from proteolytic cleavage of complement proteins are designated with lower-case letter suffixes, e.g., C3a. Inactivated fragments may be designated with the suffix 'i', e.g. C3bi. Activated components or complexes with biological activity are designated by a bar over the symbol e.g. C1 or C4b,2a. The classic pathway is activated by the binding of C1 to classic pathway activators, primarily antigen-antibody complexes containing IgM, IgG1, IgG3; C1q binds to a single IgM molecule or two adjacent IgG molecules. The alternative pathway can be activated by IgA immune complexes and also by nonimmunologic materials including bacterial endotoxins, microbial polysaccharides, and cell walls. Activation of the classic pathway triggers an enzymatic cascade involving C1, C4, C2 and C3; activation of the alternative pathway triggers a cascade involving C3 and factors B, D and P. Both result in the cleavage of C5 and the formation of the membrane attack complex. Complement activation also results in the formation of many biologically active complement fragments that act as anaphylatoxins, opsonins, or chemotactic factors. [EU] Complementary and alternative medicine: CAM. Forms of treatment that are used in addition to (complementary) or instead of (alternative) standard treatments. These practices are not considered standard medical approaches. CAM includes dietary supplements, megadose vitamins, herbal preparations, special teas, massage therapy, magnet therapy, spiritual healing, and meditation. [NIH] Complementary medicine: Practices not generally recognized by the medical community as standard or conventional medical approaches and used to enhance or complement the standard treatments. Complementary medicine includes the taking of dietary supplements, megadose vitamins, and herbal preparations; the drinking of special teas; and practices such as massage therapy, magnet therapy, spiritual healing, and meditation. [NIH] Complementation: The production of a wild-type phenotype when two different mutations are combined in a diploid or a heterokaryon and tested in trans-configuration. [NIH] Compulsions: In psychology, an irresistible urge, sometimes amounting to obsession to perform a particular act which usually is carried out against the performer's will or better judgment. [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] Computed tomography: CT scan. A series of detailed pictures of areas inside the body, taken from different angles; the pictures are created by a computer linked to an x-ray machine. Also called computerized tomography and computerized axial tomography (CAT) scan. [NIH] Computerized tomography: A series of detailed pictures of areas inside the body, taken from different angles; the pictures are created by a computer linked to an x-ray machine. Also called computerized axial tomography (CAT) scan and computed tomography (CT scan). [NIH] Concentric: Having a common center of curvature or symmetry. [NIH] Conception: The onset of pregnancy, marked by implantation of the blastocyst; the
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formation of a viable zygote. [EU] Concomitant: Accompanying; accessory; joined with another. [EU] Conduction: The transfer of sound waves, heat, nervous impulses, or electricity. [EU] Cone: One of the special retinal receptor elements which are presumed to be primarily concerned with perception of light and color stimuli when the eye is adapted to light. [NIH] Congenita: Displacement, subluxation, or malposition of the crystalline lens. [NIH] Congestive heart failure: Weakness of the heart muscle that leads to a buildup of fluid in body tissues. [NIH] Conjugated: Acting or operating as if joined; simultaneous. [EU] Connective Tissue: Tissue that supports and binds other tissues. It consists of connective tissue cells embedded in a large amount of extracellular matrix. [NIH] Connective Tissue: Tissue that supports and binds other tissues. It consists of connective tissue cells embedded in a large amount of extracellular matrix. [NIH] Connective Tissue Cells: A group of cells that includes fibroblasts, cartilage cells, adipocytes, smooth muscle cells, and bone cells. [NIH] Consciousness: Sense of awareness of self and of the environment. [NIH] Constitutional: 1. Affecting the whole constitution of the body; not local. 2. Pertaining to the constitution. [EU] Constriction: The act of constricting. [NIH] Constriction, Pathologic: The condition of an anatomical structure's being constricted beyond normal dimensions. [NIH] Contamination: The soiling or pollution by inferior material, as by the introduction of organisms into a wound, or sewage into a stream. [EU] Continuum: An area over which the vegetation or animal population is of constantly changing composition so that homogeneous, separate communities cannot be distinguished. [NIH]
Contractility: Capacity for becoming short in response to a suitable stimulus. [EU] Contracture: A condition of fixed high resistance to passive stretch of a muscle, resulting from fibrosis of the tissues supporting the muscles or the joints, or from disorders of the muscle fibres. [EU] Contraindications: Any factor or sign that it is unwise to pursue a certain kind of action or treatment, e. g. giving a general anesthetic to a person with pneumonia. [NIH] Controlled clinical trial: A clinical study that includes a comparison (control) group. The comparison group receives a placebo, another treatment, or no treatment at all. [NIH] Convulsions: A general term referring to sudden and often violent motor activity of cerebral or brainstem origin. Convulsions may also occur in the absence of an electrical cerebral discharge (e.g., in response to hypotension). [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 Diseases: Diseases of the cornea. [NIH] Corneum: The superficial layer of the epidermis containing keratinized cells. [NIH] Coronary: Encircling in the manner of a crown; a term applied to vessels; nerves, ligaments,
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etc. The term usually denotes the arteries that supply the heart muscle and, by extension, a pathologic involvement of them. [EU] Coronary heart disease: A type of heart disease caused by narrowing of the coronary arteries that feed the heart, which needs a constant supply of oxygen and nutrients carried by the blood in the coronary arteries. When the coronary arteries become narrowed or clogged by fat and cholesterol deposits and cannot supply enough blood to the heart, CHD results. [NIH] Coronary Thrombosis: Presence of a thrombus in a coronary artery, often causing a myocardial infarction. [NIH] Corpuscle: A small mass or body; a sensory nerve end bulb; a cell, especially that of the blood or the lymph. [NIH] Cortex: The outer layer of an organ or other body structure, as distinguished from the internal substance. [EU] Cortical: Pertaining to or of the nature of a cortex or bark. [EU] 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] 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] Cranial: Pertaining to the cranium, or to the anterior (in animals) or superior (in humans) end of the body. [EU] Creatine: An amino acid that occurs in vertebrate tissues and in urine. In muscle tissue, creatine generally occurs as phosphocreatine. Creatine is excreted as creatinine in the urine. [NIH]
Creatine Kinase: A transferase that catalyzes formation of phosphocreatine from ATP + creatine. The reaction stores ATP energy as phosphocreatine. Three cytoplasmic isoenzymes have been identified in human tissues: MM from skeletal muscle, MB from myocardial tissue, and BB from nervous tissue as well as a mitochondrial isoenzyme. Macro-creatine kinase refers to creatine kinase complexed with other serum proteins. EC 2.7.3.2. [NIH] Creatinine: A compound that is excreted from the body in urine. Creatinine levels are measured to monitor kidney function. [NIH] Crossing-over: The exchange of corresponding segments between chromatids of homologous chromosomes during meiosia, forming a chiasma. [NIH] Crystallization: The formation of crystals; conversion to a crystalline form. [EU] Cues: Signals for an action; that specific portion of a perceptual field or pattern of stimuli to which a subject has learned to respond. [NIH] Cultured cells: Animal or human cells that are grown in the laboratory. [NIH] Curare: Plant extracts from several species, including Strychnos toxifera, S. castelnaei, S. crevauxii, and Chondodendron tomentosum, that produce paralysis of skeletal muscle and
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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] Cytochrome: Any electron transfer hemoprotein having a mode of action in which the transfer of a single electron is effected by a reversible valence change of the central iron atom of the heme prosthetic group between the +2 and +3 oxidation states; classified as cytochromes a in which the heme contains a formyl side chain, cytochromes b, which contain protoheme or a closely similar heme that is not covalently bound to the protein, cytochromes c in which protoheme or other heme is covalently bound to the protein, and cytochromes d in which the iron-tetrapyrrole has fewer conjugated double bonds than the hemes have. Well-known cytochromes have been numbered consecutively within groups and are designated by subscripts (beginning with no subscript), e.g. cytochromes c, c1, C2, . New cytochromes are named according to the wavelength in nanometres of the absorption maximum of the a-band of the iron (II) form in pyridine, e.g., c-555. [EU] Cytogenetics: A branch of genetics which deals with the cytological and molecular behavior of genes and chromosomes during cell division. [NIH] Cytokine: Small but highly potent protein that modulates the activity of many cell types, including T and B cells. [NIH] Cytokinesis: Division of the rest of cell. [NIH] Cytoplasm: The protoplasm of a cell exclusive of that of the nucleus; it consists of a continuous aqueous solution (cytosol) and the organelles and inclusions suspended in it (phaneroplasm), and is the site of most of the chemical activities of the cell. [EU] Cytoskeleton: The network of filaments, tubules, and interconnecting filamentous bridges which give shape, structure, and organization to the cytoplasm. [NIH] Cytotoxic: Cell-killing. [NIH] Cytotoxicity: Quality of being capable of producing a specific toxic action upon cells of special organs. [NIH] Data Collection: Systematic gathering of data for a particular purpose from various sources, including questionnaires, interviews, observation, existing records, and electronic devices. The process is usually preliminary to statistical analysis of the data. [NIH] De novo: In cancer, the first occurrence of cancer in the body. [NIH] Deamination: The removal of an amino group (NH2) from a chemical compound. [NIH] Decarboxylation: The removal of a carboxyl group, usually in the form of carbon dioxide, from a chemical compound. [NIH] Decidua: The epithelial lining of the endometrium that is formed before the fertilized ovum reaches the uterus. The fertilized ovum embeds in the decidua. If the ovum is not fertilized, the decidua is shed during menstruation. [NIH] Defense Mechanisms: Unconscious process used by an individual or a group of individuals in order to cope with impulses, feelings or ideas which are not acceptable at their conscious level; various types include reaction formation, projection and self reversal. [NIH] Degenerative: Undergoing degeneration : tending to degenerate; having the character of or involving degeneration; causing or tending to cause degeneration. [EU] Dehydroepiandrosterone: DHEA. A substance that is being studied as a cancer prevention
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drug. It belongs to the family of drugs called steroids. [NIH] Deletion: A genetic rearrangement through loss of segments of DNA (chromosomes), bringing sequences, which are normally separated, into close proximity. [NIH] Dementia: An acquired organic mental disorder with loss of intellectual abilities of sufficient severity to interfere with social or occupational functioning. The dysfunction is multifaceted and involves memory, behavior, personality, judgment, attention, spatial relations, language, abstract thought, and other executive functions. The intellectual decline is usually progressive, and initially spares the level of consciousness. [NIH] Denaturation: Rupture of the hydrogen bonds by heating a DNA solution and then cooling it rapidly causes the two complementary strands to separate. [NIH] Dendrites: Extensions of the nerve cell body. They are short and branched and receive stimuli from other neurons. [NIH] Density: The logarithm to the base 10 of the opacity of an exposed and processed film. [NIH] Depolarization: The process or act of neutralizing polarity. In neurophysiology, the reversal of the resting potential in excitable cell membranes when stimulated, i.e., the tendency of the cell membrane potential to become positive with respect to the potential outside the cell. [EU] Deprivation: Loss or absence of parts, organs, powers, or things that are needed. [EU] DES: Diethylstilbestrol. A synthetic hormone that was prescribed from the early 1940s until 1971 to help women with complications of pregnancy. DES has been linked to an increased risk of clear cell carcinoma of the vagina in daughters of women who used DES. DES may also increase the risk of breast cancer in women who used DES. [NIH] Desmin: An intermediate filament protein found predominantly in smooth, skeletal, and cardiac muscle cells. Localized at the Z line. MW 50,000 to 55,000 is species dependent. [NIH] Desmosomes: Attachment bodies between cells such as in the corneal epithelium, which possibly allow tonofibrils to pass from cell to cell and which can degenerate to allow cells to migrate to cover a denuded area. [NIH] Developmental Biology: The field of biology which deals with the process of the growth and differentiation of an organism. [NIH] Diabetes Mellitus: A heterogeneous group of disorders that share glucose intolerance in common. [NIH] Diagnostic procedure: A method used to identify a disease. [NIH] Diaphragm: The musculofibrous partition that separates the thoracic cavity from the abdominal cavity. Contraction of the diaphragm increases the volume of the thoracic cavity aiding inspiration. [NIH] Diastole: Period of relaxation of the heart, especially the ventricles. [NIH] Diastolic: Of or pertaining to the diastole. [EU] 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] Dilatation: The act of dilating. [NIH] Dilated cardiomyopathy: Heart muscle disease that leads to enlargement of the heart's chambers, robbing the heart of its pumping ability. [NIH] Diploid: Having two sets of chromosomes. [NIH]
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Direct: 1. Straight; in a straight line. 2. Performed immediately and without the intervention of subsidiary means. [EU] Discrete: Made up of separate parts or characterized by lesions which do not become blended; not running together; separate. [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] Dislocation: The displacement of any part, more especially of a bone. Called also luxation. [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] Dominance: In genetics, the full phenotypic expression of a gene in both heterozygotes and homozygotes. [EU] 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] Double-blind: Pertaining to a clinical trial or other experiment in which neither the subject nor the person administering treatment knows which treatment any particular subject is receiving. [EU] 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 Resistance: Diminished or failed response of an organism, disease or tissue to the intended effectiveness of a chemical or drug. It should be differentiated from drug tolerance which is the progressive diminution of the susceptibility of a human or animal to the effects of a drug, as a result of continued administration. [NIH] Drug Tolerance: Progressive diminution of the susceptibility of a human or animal to the effects of a drug, resulting from its continued administration. It should be differentiated from drug resistance wherein an organism, disease, or tissue fails to respond to the intended effectiveness of a chemical or drug. It should also be differentiated from maximum tolerated dose and no-observed-adverse-effect level. [NIH] Duct: A tube through which body fluids pass. [NIH] Dwarfism: The condition of being undersized as a result of premature arrest of skeletal growth. It may be caused by insufficient secretion of growth hormone (pituitary dwarfism). [NIH]
Dysphagia: Difficulty in swallowing. [EU] Dysplasia: Cells that look abnormal under a microscope but are not cancer. [NIH]
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Dystonia: Disordered tonicity of muscle. [EU] Dystrophic: Pertaining to toxic habitats low in nutrients. [NIH] 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] Ectopic: Pertaining to or characterized by ectopia. [EU] Effector: It is often an enzyme that converts an inactive precursor molecule into an active second messenger. [NIH] Efferent: Nerve fibers which conduct impulses from the central nervous system to muscles and glands. [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] Elastic: Susceptible of resisting and recovering from stretching, compression or distortion applied by a force. [EU] Elastin: The protein that gives flexibility to tissues. [NIH] Elective: Subject to the choice or decision of the patient or physician; applied to procedures that are advantageous to the patient but not urgent. [EU] Electrocardiogram: Measurement of electrical activity during heartbeats. [NIH] Electrocardiography: Recording of the moment-to-moment electromotive forces of the heart as projected onto various sites on the body's surface, delineated as a scalar function of time. [NIH]
Electroencephalography: Recording of electric currents developed in the brain by means of electrodes applied to the scalp, to the surface of the brain, or placed within the substance of the brain. [NIH] Electrolyte: A substance that dissociates into ions when fused or in solution, and thus becomes capable of conducting electricity; an ionic solute. [EU] Electron microscope: A microscope (device used to magnify small objects) that uses electrons (instead of light) to produce an enlarged image. An electron microscopes shows tiny details better than any other type of microscope. [NIH] Electrophoresis: An electrochemical process in which macromolecules or colloidal particles with a net electric charge migrate in a solution under the influence of an electric current. [NIH]
Electrophysiological: Pertaining to electrophysiology, that is a branch of physiology that is concerned with the electric phenomena associated with living bodies and involved in their functional activity. [EU] Electroretinography: Recording of electric potentials in the retina after stimulation by light. [NIH]
Elementary Particles: Individual components of atoms, usually subatomic; subnuclear particles are usually detected only when the atomic nucleus decays and then only
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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] Embryogenesis: The process of embryo or embryoid formation, whether by sexual (zygotic) or asexual means. In asexual embryogenesis embryoids arise directly from the explant or on intermediary callus tissue. In some cases they arise from individual cells (somatic cell embryoge). [NIH] Embryology: The study of the development of an organism during the embryonic and fetal stages of life. [NIH] 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] Enamel: A very hard whitish substance which covers the dentine of the anatomical crown of a tooth. [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]
Endemic: Present or usually prevalent in a population or geographical area at all times; said of a disease or agent. Called also endemial. [EU] Endocytosis: Cellular uptake of extracellular materials within membrane-limited vacuoles or microvesicles. Endosomes play a central role in endocytosis. [NIH] Endogenous: Produced inside an organism or cell. The opposite is external (exogenous) production. [NIH] Endometrium: The layer of tissue that lines the uterus. [NIH] Endothelial cell: The main type of cell found in the inside lining of blood vessels, lymph vessels, and the heart. [NIH] Endothelium: A layer of epithelium that lines the heart, blood vessels (endothelium, vascular), lymph vessels (endothelium, lymphatic), and the serous cavities of the body. [NIH] Endothelium-derived: Small molecule that diffuses to the adjacent muscle layer and relaxes it. [NIH] Endotoxin: Toxin from cell walls of bacteria. [NIH] End-stage renal: Total chronic kidney failure. When the kidneys fail, the body retains fluid and harmful wastes build up. A person with ESRD needs treatment to replace the work of the failed kidneys. [NIH] Enhancer: Transcriptional element in the virus genome. [NIH] Enterocytes: Terminally differentiated cells comprising the majority of the external surface of the intestinal epithelium (see intestinal mucosa). Unlike goblet cells, they do not produce
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or secrete mucins, nor do they secrete cryptdins as do the paneth cells. [NIH] Enterovirus: A genus of the family Picornaviridae whose members preferentially inhabit the intestinal tract of a variety of hosts. The genus contains many species. Newly described members of human enteroviruses are assigned continuous numbers with the species designated "human enterovirus". [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] Eosinophilic: A condition found primarily in grinding workers caused by a reaction of the pulmonary tissue, in particular the eosinophilic cells, to dust that has entered the lung. [NIH] Eosinophils: Granular leukocytes with a nucleus that usually has two lobes connected by a slender thread of chromatin, and cytoplasm containing coarse, round granules that are uniform in size and stainable by eosin. [NIH] Epidemic: Occurring suddenly in numbers clearly in excess of normal expectancy; said especially of infectious diseases but applied also to any disease, injury, or other healthrelated event occurring in such outbreaks. [EU] Epidermal: Pertaining to or resembling epidermis. Called also epidermic or epidermoid. [EU] Epidermal Growth Factor: A 6 kD polypeptide growth factor initially discovered in mouse submaxillary glands. Human epidermal growth factor was originally isolated from urine based on its ability to inhibit gastric secretion and called urogastrone. epidermal growth factor exerts a wide variety of biological effects including the promotion of proliferation and differentiation of mesenchymal and epithelial cells. [NIH] Epidermis: Nonvascular layer of the skin. It is made up, from within outward, of five layers: 1) basal layer (stratum basale epidermidis); 2) spinous layer (stratum spinosum epidermidis); 3) granular layer (stratum granulosum epidermidis); 4) clear layer (stratum lucidum epidermidis); and 5) horny layer (stratum corneum epidermidis). [NIH] Epidermolysis Bullosa: Group of genetically determined disorders characterized by the blistering of skin and mucosae. There are four major forms: acquired, simple, junctional, and dystrophic. Each of the latter three has several varieties. [NIH] Epidermolysis Bullosa Simplex: Form of epidermolysis bullosa characterized by autosomal dominant inheritance and by serous bullae that heal without scarring. [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] Epistasis: The degree of dominance exerted by one gene on the expression of a non-allelic gene. [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
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covers the inner or outer surfaces of the body. [NIH] Epitope: A molecule or portion of a molecule capable of binding to the combining site of an antibody. For every given antigenic determinant, the body can construct a variety of antibody-combining sites, some of which fit almost perfectly, and others which barely fit. [NIH]
Erythrocyte Membrane: The semipermeable outer portion of the red corpuscle. It is known as a 'ghost' after hemolysis. [NIH] Erythrocytes: Red blood cells. Mature erythrocytes are non-nucleated, biconcave disks containing hemoglobin whose function is to transport oxygen. [NIH] Esophageal: Having to do with the esophagus, the muscular tube through which food passes from the throat to the stomach. [NIH] Esophagus: The muscular tube through which food passes from the throat to the stomach. [NIH]
Eukaryotic Cells: Cells of the higher organisms, containing a true nucleus bounded by a nuclear membrane. [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] Excitotoxicity: Excessive exposure to glutamate or related compounds can kill brain neurons, presumably by overstimulating them. [NIH] Exhaustion: The feeling of weariness of mind and body. [NIH] Exocytosis: Cellular release of material within membrane-limited vesicles by fusion of the vesicles with the cell membrane. [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] Expiration: The act of breathing out, or expelling air from the lungs. [EU] External-beam radiation: Radiation therapy that uses a machine to aim high-energy rays at the cancer. Also called external radiation. [NIH] Extracellular: Outside a cell or cells. [EU] Extracellular Matrix: A meshwork-like substance found within the extracellular space and in association with the basement membrane of the cell surface. It promotes cellular proliferation and provides a supporting structure to which cells or cell lysates in culture dishes adhere. [NIH] Extracellular Matrix Proteins: Macromolecular organic compounds that contain carbon, hydrogen, oxygen, nitrogen, and usually, sulfur. These macromolecules (proteins) form an intricate meshwork in which cells are embedded to construct tissues. Variations in the relative types of macromolecules and their organization determine the type of extracellular matrix, each adapted to the functional requirements of the tissue. The two main classes of macromolecules that form the extracellular matrix are: glycosaminoglycans, usually linked to proteins (proteoglycans), and fibrous proteins (e.g., collagen, elastin, fibronectins and laminin). [NIH] Extracellular Space: Interstitial space between cells, occupied by fluid as well as amorphous and fibrous substances. [NIH] Extravasation: A discharge or escape, as of blood, from a vessel into the tissues. [EU] Extremity: A limb; an arm or leg (membrum); sometimes applied specifically to a hand or
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foot. [EU] Eye Infections: Infection, moderate to severe, caused by bacteria, fungi, or viruses, which occurs either on the external surface of the eye or intraocularly with probable inflammation, visual impairment, or blindness. [NIH] Eye Movements: Voluntary or reflex-controlled movements of the eye. [NIH] Facial: Of or pertaining to the face. [EU] Facial Expression: Observable changes of expression in the face in response to emotional stimuli. [NIH] Facial Nerve: The 7th cranial nerve. The facial nerve has two parts, the larger motor root which may be called the facial nerve proper, and the smaller intermediate or sensory root. Together they provide efferent innervation to the muscles of facial expression and to the lacrimal and salivary glands, and convey afferent information for taste from the anterior two-thirds of the tongue and for touch from the external ear. [NIH] Failure to Thrive: A condition in which an infant or child's weight gain and growth are far below usual levels for age. [NIH] Family Planning: Programs or services designed to assist the family in controlling reproduction by either improving or diminishing fertility. [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] Femoral: Pertaining to the femur, or to the thigh. [EU] Femoral Artery: The main artery of the thigh, a continuation of the external iliac artery. [NIH] Femur: The longest and largest bone of the skeleton, it is situated between the hip and the knee. [NIH] Ferritin: An iron-containing protein complex that is formed by a combination of ferric iron with the protein apoferritin. [NIH] Fetal Alcohol Syndrome: A disorder occurring in children born to alcoholic women who continue to drink heavily during pregnancy. Common abnormalities are growth deficiency (prenatal and postnatal), altered morphogenesis, mental deficiency, and characteristic facies - small eyes and flattened nasal bridge. Fine motor dysfunction and tremulousness are observed in the newborn. [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] Fibrillation: A small, local, involuntary contraction of muscle, invisible under the skin, resulting from spontaneous activation of single muscle cells or muscle fibres. [EU] Fibrin: A protein derived from fibrinogen in the presence of thrombin, which forms part of the blood clot. [NIH] Fibrinogen: Plasma glycoprotein clotted by thrombin, composed of a dimer of three non-
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identical pairs of polypeptide chains (alpha, beta, gamma) held together by disulfide bonds. Fibrinogen clotting is a sol-gel change involving complex molecular arrangements: whereas fibrinogen is cleaved by thrombin to form polypeptides A and B, the proteolytic action of other enzymes yields different fibrinogen degradation products. [NIH] Fibrinolysis: The natural enzymatic dissolution of fibrin. [NIH] Fibroblast Growth Factor: Peptide isolated from the pituitary gland and from the brain. It is a potent mitogen which stimulates growth of a variety of mesodermal cells including chondrocytes, granulosa, and endothelial cells. The peptide may be active in wound healing and animal limb regeneration. [NIH] Fibroblasts: Connective tissue cells which secrete an extracellular matrix rich in collagen and other macromolecules. [NIH] Fibronectins: Glycoproteins found on the surfaces of cells, particularly in fibrillar structures. The proteins are lost or reduced when these cells undergo viral or chemical transformation. They are highly susceptible to proteolysis and are substrates for activated blood coagulation factor VIII. The forms present in plasma are called cold-insoluble globulins. [NIH] Fibrosis: Any pathological condition where fibrous connective tissue invades any organ, usually as a consequence of inflammation or other injury. [NIH] Fine-needle aspiration: The removal of tissue or fluid with a needle for examination under a microscope. Also called needle biopsy. [NIH] Fissure: Any cleft or groove, normal or otherwise; especially a deep fold in the cerebral cortex which involves the entire thickness of the brain wall. [EU] 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] Flaccid: Weak, lax and soft. [EU] Flexion: In gynaecology, a displacement of the uterus in which the organ is bent so far forward or backward that an acute angle forms between the fundus and the cervix. [EU] 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] Flutter: A rapid vibration or pulsation. [EU] Fold: A plication or doubling of various parts of the body. [NIH] Forearm: The part between the elbow and the wrist. [NIH] Founder Effect: The principle that when a small subgroup of a larger population establishes
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itself as a separate and isolated entity, its gene pool carries only a fraction of the genetic diversity of the parental population. This may result in an increased frequency of certain diseases in the subgroup, especially those diseases known to be autosomal recessive. [NIH] Fovea: The central part of the macula that provides the sharpest vision. [NIH] Frameshift: A type of mutation which causes out-of-phase transcription of the base sequence; such mutations arise from the addition or delection of nucleotide(s) in numbers other than 3 or multiples of 3. [NIH] Frameshift Mutation: A type of mutation in which a number of nucleotides not divisible by three is deleted from or inserted into a coding sequence, thereby causing an alteration in the reading frame of the entire sequence downstream of the mutation. These mutations may be induced by certain types of mutagens or may occur spontaneously. [NIH] Free Radicals: Highly reactive molecules with an unsatisfied electron valence pair. Free radicals are produced in both normal and pathological processes. They are proven or suspected agents of tissue damage in a wide variety of circumstances including radiation, damage from environment chemicals, and aging. Natural and pharmacological prevention of free radical damage is being actively investigated. [NIH] Friction: Surface resistance to the relative motion of one body against the rubbing, sliding, rolling, or flowing of another with which it is in contact. [NIH] Frontal Lobe: The anterior part of the cerebral hemisphere. [NIH] Fructose: A type of sugar found in many fruits and vegetables and in honey. Fructose is used to sweeten some diet foods. It is considered a nutritive sweetener because it has calories. [NIH] Fundus: The larger part of a hollow organ that is farthest away from the organ's opening. The bladder, gallbladder, stomach, uterus, eye, and cavity of the middle ear all have a fundus. [NIH] Fungi: A kingdom of eukaryotic, heterotrophic organisms that live as saprobes or parasites, including mushrooms, yeasts, smuts, molds, etc. They reproduce either sexually or asexually, and have life cycles that range from simple to complex. Filamentous fungi refer to those that grow as multicelluar colonies (mushrooms and molds). [NIH] Gait: Manner or style of walking. [NIH] Gallbladder: The pear-shaped organ that sits below the liver. Bile is concentrated and stored in the gallbladder. [NIH] Gametogenesis: The first phase of sexual reproduction which involves the transforming of certain cells in the parent into specialized reproductive cells. [NIH] Ganglia: Clusters of multipolar neurons surrounded by a capsule of loosely organized connective tissue located outside the central nervous system. [NIH] Gas: Air that comes from normal breakdown of food. The gases are passed out of the body through the rectum (flatus) or the mouth (burp). [NIH] Gas exchange: Primary function of the lungs; transfer of oxygen from inhaled air into the blood and of carbon dioxide from the blood into the lungs. [NIH] Gastric: Having to do with the stomach. [NIH] Gastrin: A hormone released after eating. Gastrin causes the stomach to produce more acid. [NIH]
Gastroenterology: A subspecialty of internal medicine concerned with the study of the physiology and diseases of the digestive system and related structures (esophagus, liver, gallbladder, and pancreas). [NIH]
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Gastrointestinal: Refers to the stomach and intestines. [NIH] Gastrostomy: Creation of an artificial external opening into the stomach for nutritional support or gastrointestinal compression. [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 Deletion: A genetic rearrangement through loss of segments of DNA or RNA, bringing sequences which are normally separated into close proximity. This deletion may be detected using cytogenetic techniques and can also be inferred from the phenotype, indicating a deletion at one specific locus. [NIH] Gene Duplication: It encodes the major envelope protein and includes all the specifications for HBsAg. [NIH] Gene Expression: The phenotypic manifestation of a gene or genes by the processes of gene action. [NIH] Gene Expression Profiling: The determination of the pattern of genes expressed i.e., transcribed, under specific circumstances or in a specific cell. [NIH] Gene Rearrangement: The ordered rearrangement of gene regions by DNA recombination such as that which occurs normally during development. [NIH] Gene Silencing: Interruption or suppression of the expression of a gene at transcriptional or translational levels. [NIH] Gene Targeting: The integration of exogenous DNA into the genome of an organism at sites where its expression can be suitably controlled. This integration occurs as a result of homologous recombination. [NIH] Gene Therapy: The introduction of new genes into cells for the purpose of treating disease by restoring or adding gene expression. Techniques include insertion of retroviral vectors, transfection, homologous recombination, and injection of new genes into the nuclei of single cell embryos. The entire gene therapy process may consist of multiple steps. The new genes may be introduced into proliferating cells in vivo (e.g., bone marrow) or in vitro (e.g., fibroblast cultures) and the modified cells transferred to the site where the gene expression is required. Gene therapy may be particularly useful for treating enzyme deficiency diseases, hemoglobinopathies, and leukemias and may also prove useful in restoring drug sensitivity, particularly for leukemia. [NIH] Genetic Code: The specifications for how information, stored in nucleic acid sequence (base sequence), is translated into protein sequence (amino acid sequence). The start, stop, and order of amino acids of a protein is specified by consecutive triplets of nucleotides called codons (codon). [NIH] Genetic Counseling: Advising families of the risks involved pertaining to birth defects, in order that they may make an informed decision on current or future pregnancies. [NIH] Genetic Engineering: Directed modification of the gene complement of a living organism by such techniques as altering the DNA, substituting genetic material by means of a virus, transplanting whole nuclei, transplanting cell hybrids, etc. [NIH] Genetic testing: Analyzing DNA to look for a genetic alteration that may indicate an increased risk for developing a specific disease or disorder. [NIH] Genetic transcription: The process by which the genetic information encoded in the gene,
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represented as a linear sequence of deoxyribonucleotides, is copied into an exactly complementary sequence of ribonucleotides known as messenger RNA. [NIH] Genetics: The biological science that deals with the phenomena and mechanisms of heredity. [NIH] Genital: Pertaining to the genitalia. [EU] Genomics: The systematic study of the complete DNA sequences (genome) of organisms. [NIH]
Genotype: The genetic constitution of the individual; the characterization of the genes. [NIH] Germ Cells: The reproductive cells in multicellular organisms. [NIH] Germ-Line Mutation: Any detectable and heritable alteration in the lineage of germ cells. Mutations in these cells (i.e., "generative" cells ancestral to the gametes) are transmitted to progeny while those in somatic cells are not. [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] Glucocorticoid: A compound that belongs to the family of compounds called corticosteroids (steroids). Glucocorticoids affect metabolism and have anti-inflammatory and immunosuppressive effects. They may be naturally produced (hormones) or synthetic (drugs). [NIH] Glucose: D-Glucose. A primary source of energy for living organisms. It is naturally occurring and is found in fruits and other parts of plants in its free state. It is used therapeutically in fluid and nutrient replacement. [NIH] Glucuronic Acid: Derivatives of uronic acid found throughout the plant and animal kingdoms. They detoxify drugs and toxins by conjugating with them to form glucuronides in the liver which are more water-soluble metabolites that can be easily eliminated from the body. [NIH] Glutamate: Excitatory neurotransmitter of the brain. [NIH] Glutamic Acid: A non-essential amino acid naturally occurring in the L-form. Glutamic acid (glutamate) is the most common excitatory neurotransmitter in the central nervous system. [NIH]
Glutamine: A non-essential amino acid present abundantly throught the body and is involved in many metabolic processes. It is synthesized from glutamic acid and ammonia. It is the principal carrier of nitrogen in the body and is an important energy source for many cells. [NIH] Glutathione Peroxidase: An enzyme catalyzing the oxidation of 2 moles of glutathione in the presence of hydrogen peroxide to yield oxidized glutathione and water. EC 1.11.1.9. [NIH]
Glycine: A non-essential amino acid. It is found primarily in gelatin and silk fibroin and used therapeutically as a nutrient. It is also a fast inhibitory neurotransmitter. [NIH] Glycogen: A sugar stored in the liver and muscles. It releases glucose into the blood when cells need it for energy. Glycogen is the chief source of stored fuel in the body. [NIH] Glycogen Storage Disease: A group of inherited metabolic disorders involving the enzymes responsible for the synthesis and degradation of glycogen. In some patients, prominent liver involvement is presented. In others, more generalized storage of glycogen occurs,
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sometimes with prominent cardiac involvement. [NIH] Glycoprotein: A protein that has sugar molecules attached to it. [NIH] Glycosaminoglycans: Heteropolysaccharides which contain an N-acetylated hexosamine in a characteristic repeating disaccharide unit. The repeating structure of each disaccharide involves alternate 1,4- and 1,3-linkages consisting of either N-acetylglucosamine or Nacetylgalactosamine. [NIH] 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] Goblet Cells: Cells of the epithelial lining that produce and secrete mucins. [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]
Graft: Healthy skin, bone, or other tissue taken from one part of the body and used to replace diseased or injured tissue removed from another part of the body. [NIH] Graft Survival: The survival of a graft in a host, the factors responsible for the survival and the changes occurring within the graft during growth in the host. [NIH] Grafting: The operation of transfer of tissue from one site to another. [NIH] Granulocytes: Leukocytes with abundant granules in the cytoplasm. They are divided into three groups: neutrophils, eosinophils, and basophils. [NIH] Gravis: Eruption of watery blisters on the skin among those handling animals and animal products. [NIH] Growth: The progressive development of a living being or part of an organism from its earliest stage to maturity. [NIH] Growth factors: Substances made by the body that function to regulate cell division and cell survival. Some growth factors are also produced in the laboratory and used in biological therapy. [NIH] Guanine: One of the four DNA bases. [NIH] Guanylate Cyclase: An enzyme that catalyzes the conversion of GTP to 3',5'-cyclic GMP and pyrophosphate. It also acts on ITP and dGTP. (From Enzyme Nomenclature, 1992) EC 4.6.1.2. [NIH] Hammer: The largest of the three ossicles of the ear. [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
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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] Heart attack: A seizure of weak or abnormal functioning of the heart. [NIH] Heart failure: Loss of pumping ability by the heart, often accompanied by fatigue, breathlessness, and excess fluid accumulation in body tissues. [NIH] Heartbeat: One complete contraction of the heart. [NIH] Heat-Shock Proteins: Proteins which are synthesized in eukaryotic organisms and bacteria in response to hyperthermia and other environmental stresses. They increase thermal tolerance and perform functions essential to cell survival under these conditions. [NIH] Heat-Shock Proteins 90: A class of molecular chaperones whose members act in the mechanism of signal transduction by steroid receptors. [NIH] Hematopoietic Stem Cells: Progenitor cells from which all blood cells derive. [NIH] Heme: The color-furnishing portion of hemoglobin. It is found free in tissues and as the prosthetic group in many hemeproteins. [NIH] Hemidesmosomes: An anchoring junction of the cell to a non-cellular substrate, similar in morphology to halves of desmosomes. They are composed of specialized areas of the plasma membrane where intermediate filaments bind on the cytoplasmic face to the transmembrane linkers, integrins, via intracellular attachment proteins, while the extracellular domain of the integrins binds to extracellular matrix proteins. [NIH] Hemochromatosis: A disease that occurs when the body absorbs too much iron. The body stores the excess iron in the liver, pancreas, and other organs. May cause cirrhosis of the liver. Also called iron overload disease. [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] Hemoglobinopathies: A group of inherited disorders characterized by structural alterations within the hemoglobin molecule. [NIH] Hemolysis: The destruction of erythrocytes by many different causal agents such as antibodies, bacteria, chemicals, temperature, and changes in tonicity. [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] Hemophilia: Refers to a group of hereditary disorders in which affected individuals fail to make enough of certain proteins needed to form blood clots. [NIH] Hemorrhage: Bleeding or escape of blood from a vessel. [NIH] Hemostasis: The process which spontaneously arrests the flow of blood from vessels carrying blood under pressure. It is accomplished by contraction of the vessels, adhesion and aggregation of formed blood elements, and the process of blood or plasma coagulation. [NIH]
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Heparan Sulfate Proteoglycan: A substance released by astrocytes, which is critical in stopping nervous fibers in their tracks. [NIH] Heparin: Heparinic acid. A highly acidic mucopolysaccharide formed of equal parts of sulfated D-glucosamine and D-glucuronic acid with sulfaminic bridges. The molecular weight ranges from six to twenty thousand. Heparin occurs in and is obtained from liver, lung, mast cells, etc., of vertebrates. Its function is unknown, but it is used to prevent blood clotting in vivo and vitro, in the form of many different salts. [NIH] Heparin-binding: Protein that stimulates the proliferation of endothelial cells. [NIH] Hepatic: Refers to the liver. [NIH] Hepatocyte: A liver cell. [NIH] Hepatocyte Growth Factor: Multifunctional growth factor which regulates both cell growth and cell motility. It exerts a strong mitogenic effect on hepatocytes and primary epithelial cells. Its receptor is proto-oncogene protein C-met. [NIH] Hepatoma: A liver tumor. [NIH] Hereditary: Of, relating to, or denoting factors that can be transmitted genetically from one generation to another. [NIH] Heredity: 1. The genetic transmission of a particular quality or trait from parent to offspring. 2. The genetic constitution of an individual. [EU] Herpetiformis: Duhring's disease a recurring, inflammatory disease of the skin of unknown etiology characterized by erythematous, papular, pustular, or vesicular lesions which tend to group and are accompanied by itching and burning. [NIH] Heterochromatin: The portion of chromosome material that remains condensed and is transcriptionally inactive during interphase. [NIH] Heterodimers: Zippered pair of nonidentical proteins. [NIH] Heterogeneity: The property of one or more samples or populations which implies that they are not identical in respect of some or all of their parameters, e. g. heterogeneity of variance. [NIH]
Heterogenic: Derived from a different source or species. Also called heterogenous. [NIH] Heterogenous: Derived from a different source or species. Also called heterogenic. [NIH] Heterozygotes: Having unlike alleles at one or more corresponding loci on homologous chromosomes. [NIH] Histamine: 1H-Imidazole-4-ethanamine. A depressor amine derived by enzymatic decarboxylation of histidine. It is a powerful stimulant of gastric secretion, a constrictor of bronchial smooth muscle, a vasodilator, and also a centrally acting neurotransmitter. [NIH] Histidine: An essential amino acid important in a number of metabolic processes. It is required for the production of histamine. [NIH] Histology: The study of tissues and cells under a microscope. [NIH] Holidays: Days commemorating events. Holidays also include vacation periods. [NIH] Homeostasis: The processes whereby the internal environment of an organism tends to remain balanced and stable. [NIH] Homeotic: Characterizes genes the mutations of which lead to inappropriate expressions of characteristics normally associated with another part of the organism (homeotic mutants). [NIH]
Homodimer: Protein-binding "activation domains" always combine with identical proteins. [NIH]
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Homogenate: A suspension of animal tissue that is ground in the all-glass "homogenizer" described by Potter and Elvehjem in 1936. [NIH] Homogeneous: Consisting of or composed of similar elements or ingredients; of a uniform quality throughout. [EU] Homologous: Corresponding in structure, position, origin, etc., as (a) the feathers of a bird and the scales of a fish, (b) antigen and its specific antibody, (c) allelic chromosomes. [EU] Hormonal: Pertaining to or of the nature of a hormone. [EU] Hormone: A substance in the body that regulates certain organs. Hormones such as gastrin help in breaking down food. Some hormones come from cells in the stomach and small intestine. [NIH] Horny layer: The superficial layer of the epidermis containing keratinized cells. [NIH] Host: Any animal that receives a transplanted graft. [NIH] Humeral: 1. Of, relating to, or situated in the region of the humerus: brachial. 2. Of or belonging to the shoulder. 3. Of, relating to, or being any of several body parts that are analogous in structure, function, or location to the humerus or shoulder. [EU] Humoral: Of, relating to, proceeding from, or involving a bodily humour - now often used of endocrine factors as opposed to neural or somatic. [EU] Humour: 1. A normal functioning fluid or semifluid of the body (as the blood, lymph or bile) especially of vertebrates. 2. A secretion that is itself an excitant of activity (as certain hormones). [EU] Hybrid: Cross fertilization between two varieties or, more usually, two species of vines, see also crossing. [NIH] Hybridization: The genetic process of crossbreeding to produce a hybrid. Hybrid nucleic acids can be formed by nucleic acid hybridization of DNA and RNA molecules. Protein hybridization allows for hybrid proteins to be formed from polypeptide chains. [NIH] Hydrogen: The first chemical element in the periodic table. It has the atomic symbol H, atomic number 1, and atomic weight 1. It exists, under normal conditions, as a colorless, odorless, tasteless, diatomic gas. Hydrogen ions are protons. Besides the common H1 isotope, hydrogen exists as the stable isotope deuterium and the unstable, radioactive isotope tritium. [NIH] Hydrogen Peroxide: A strong oxidizing agent used in aqueous solution as a ripening agent, bleach, and topical anti-infective. It is relatively unstable and solutions deteriorate over time unless stabilized by the addition of acetanilide or similar organic materials. [NIH] Hydrolysis: The process of cleaving a chemical compound by the addition of a molecule of water. [NIH] Hydrops Fetalis: Edema of the entire body due to abnormal accumulation of serous fluid in the tissues, associated with severe anemia and occurring in fetal erythroblastosis. [NIH] Hydroxylysine: A hydroxylated derivative of the amino acid lysine that is present in certain collagens. [NIH] Hydroxyproline: A hydroxylated form of the imino acid proline. A deficiency in ascorbic acid can result in impaired hydroxyproline formation. [NIH] Hyperphagia: Ingestion of a greater than optimal quantity of food. [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]
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Hypertension: Persistently high arterial blood pressure. Currently accepted threshold levels are 140 mm Hg systolic and 90 mm Hg diastolic pressure. [NIH] Hyperthermia: A type of treatment in which body tissue is exposed to high temperatures to damage and kill cancer cells or to make cancer cells more sensitive to the effects of radiation and certain anticancer drugs. [NIH] Hypertrophic cardiomyopathy: Heart muscle disease that leads to thickening of the heart walls, interfering with the heart's ability to fill with and pump blood. [NIH] Hypertrophy: General increase in bulk of a part or organ, not due to tumor formation, nor to an increase in the number of cells. [NIH] Hyperuricemia: A buildup of uric acid (a byproduct of metabolism) in the blood; a side effect of some anticancer drugs. [NIH] Hypogonadism: Condition resulting from or characterized by abnormally decreased functional activity of the gonads, with retardation of growth and sexual development. [NIH] Hypoplasia: Incomplete development or underdevelopment of an organ or tissue. [EU] Hypotensive: Characterized by or causing diminished tension or pressure, as abnormally low blood pressure. [EU] 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] Hypotonia: A condition of diminished tone of the skeletal muscles; diminished resistance of muscles to passive stretching. [EU] Hypoventilation: A reduction in the amount of air entering the pulmonary alveoli. [NIH] Ichthyosis: Any of several generalized skin disorders characterized by dryness, roughness, and scaliness, due to hypertrophy of the stratum corneum epidermis. Most are genetic, but some are acquired, developing in association with other systemic disease or genetic syndrome. [NIH] Ichthyosis Vulgaris: Most common form of ichthyosis characterized by prominent scaling especially on the exterior surfaces of the extremities. It is inherited as an autosomal dominant trait. [NIH] Id: The part of the personality structure which harbors the unconscious instinctive desires and strivings of the individual. [NIH] Iliac Artery: Either of two large arteries originating from the abdominal aorta; they supply blood to the pelvis, abdominal wall and legs. [NIH] Immune function: Production and action of cells that fight disease or infection. [NIH] Immune response: The activity of the immune system against foreign substances (antigens). [NIH]
Immune system: The organs, cells, and molecules responsible for the recognition and disposal of foreign ("non-self") material which enters the body. [NIH] Immunity: Nonsusceptibility to the invasive or pathogenic microorganisms or to the toxic effect of antigenic substances. [NIH]
effects
of
foreign
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] Immunoglobulin: A protein that acts as an antibody. [NIH] Immunohistochemistry: Histochemical localization of immunoreactive substances using labeled antibodies as reagents. [NIH]
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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] Impairment: In the context of health experience, an impairment is any loss or abnormality of psychological, physiological, or anatomical structure or function. [NIH] Implant radiation: A procedure in which radioactive material sealed in needles, seeds, wires, or catheters is placed directly into or near the tumor. Also called [NIH] Implantation: The insertion or grafting into the body of biological, living, inert, or radioactive material. [EU] In situ: In the natural or normal place; confined to the site of origin without invasion of neighbouring tissues. [EU] In Situ Hybridization: A technique that localizes specific nucleic acid sequences within intact chromosomes, eukaryotic cells, or bacterial cells through the use of specific nucleic acid-labeled probes. [NIH] In vitro: In the laboratory (outside the body). The opposite of in vivo (in the body). [NIH] In vivo: In the body. The opposite of in vitro (outside the body or in the laboratory). [NIH] Incision: A cut made in the body during surgery. [NIH] 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] Infant Mortality: Perinatal, neonatal, and infant deaths in a given population. [NIH] Infant, Newborn: An infant during the first month after birth. [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]
Infusion: A method of putting fluids, including drugs, into the bloodstream. Also called intravenous infusion. [NIH]
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Initiation: Mutation induced by a chemical reactive substance causing cell changes; being a step in a carcinogenic process. [NIH] Inlay: In dentistry, a filling first made to correspond with the form of a dental cavity and then cemented into the cavity. [NIH] Innervation: 1. The distribution or supply of nerves to a part. 2. The supply of nervous energy or of nerve stimulus sent to a part. [EU] Insecticides: Pesticides designed to control insects that are harmful to man. The insects may be directly harmful, as those acting as disease vectors, or indirectly harmful, as destroyers of crops, food products, or textile fabrics. [NIH] Insertional: A technique in which foreign DNA is cloned into a restriction site which occupies a position within the coding sequence of a gene in the cloning vector molecule. Insertion interrupts the gene's sequence such that its original function is no longer expressed. [NIH] Insight: The capacity to understand one's own motives, to be aware of one's own psychodynamics, to appreciate the meaning of symbolic behavior. [NIH] 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] Insulin-like: Muscular growth factor. [NIH] Integrins: A family of transmembrane glycoproteins consisting of noncovalent heterodimers. They interact with a wide variety of ligands including extracellular matrix glycoproteins, complement, and other cells, while their intracellular domains interact with the cytoskeleton. The integrins consist of at least three identified families: the cytoadhesin receptors, the leukocyte adhesion receptors, and the very-late-antigen receptors. Each family contains a common beta-subunit combined with one or more distinct alpha-subunits. These receptors participate in cell-matrix and cell-cell adhesion in many physiologically important processes, including embryological development, hemostasis, thrombosis, wound healing, immune and nonimmune defense mechanisms, and oncogenic transformation. [NIH] Intercellular Junctions: Strictly, and so far as it can be distinguished, the amorphous isotropic layer between adjacent primary walls of cells. [NIH] Interferon: A biological response modifier (a substance that can improve the body's natural response to disease). Interferons interfere with the division of cancer cells and can slow tumor growth. There are several types of interferons, including interferon-alpha, -beta, and gamma. These substances are normally produced by the body. They are also made in the laboratory for use in treating cancer and other diseases. [NIH] Interferon-alpha: One of the type I interferons produced by peripheral blood leukocytes or lymphoblastoid cells when exposed to live or inactivated virus, double-stranded RNA, or bacterial products. It is the major interferon produced by virus-induced leukocyte cultures and, in addition to its pronounced antiviral activity, it causes activation of NK cells. [NIH] Intermediate Filament Proteins: Filaments 7-11 nm in diameter found in the cytoplasm of all cells. Many specific proteins belong to this group, e.g., desmin, vimentin, prekeratin,
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decamin, skeletin, neurofilin, neurofilament protein, and glial fibrillary acid protein. [NIH] Intermediate Filaments: Cytoplasmic filaments intermediate in diameter (about 10 nanometers) between the microfilaments and the microtubules. They may be composed of any of a number of different proteins and form a ring around the cell nucleus. [NIH] Intermittent: Occurring at separated intervals; having periods of cessation of activity. [EU] Internal Medicine: A medical specialty concerned with the diagnosis and treatment of diseases of the internal organ systems of adults. [NIH] Internal radiation: A procedure in which radioactive material sealed in needles, seeds, wires, or catheters is placed directly into or near the tumor. Also called brachytherapy, implant radiation, or interstitial radiation therapy. [NIH] Interphase: The interval between two successive cell divisions during which the chromosomes are not individually distinguishable and DNA replication occurs. [NIH] Interstitial: Pertaining to or situated between parts or in the interspaces of a tissue. [EU] 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 Hypertension: Increased pressure within the cranial vault. This may result from several conditions, including hydrocephalus; brain edema; intracranial masses; severe systemic hypertension; pseudotumor cerebri; and other disorders. [NIH] Intramuscular: IM. Within or into muscle. [NIH] Intraperitoneal: IP. Within the peritoneal cavity (the area that contains the abdominal organs). [NIH] Intravascular: Within a vessel or vessels. [EU] Intravenous: IV. Into a vein. [NIH] Intrinsic: Situated entirely within or pertaining exclusively to a part. [EU] Introns: Non-coding, intervening sequences of DNA that are transcribed, but are removed from within the primary gene transcript and rapidly degraded during maturation of messenger RNA. Most genes in the nuclei of eukaryotes contain introns, as do mitochondrial and chloroplast genes. [NIH] Intubation: Introduction of a tube into a hollow organ to restore or maintain patency if obstructed. It is differentiated from catheterization in that the insertion of a catheter is usually performed for the introducing or withdrawing of fluids from the body. [NIH] Invasive: 1. Having the quality of invasiveness. 2. Involving puncture or incision of the skin or insertion of an instrument or foreign material into the body; said of diagnostic techniques. [EU]
Invertebrates: Animals that have no spinal column. [NIH] Involuntary: Reaction occurring without intention or volition. [NIH] Involution: 1. A rolling or turning inward. 2. One of the movements involved in the gastrulation of many animals. 3. A retrograde change of the entire body or in a particular organ, as the retrograde changes in the female genital organs that result in normal size after delivery. 4. The progressive degeneration occurring naturally with advancing age, resulting
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in shrivelling of organs or tissues. [EU] Iodine: A nonmetallic element of the halogen group that is represented by the atomic symbol I, atomic number 53, and atomic weight of 126.90. It is a nutritionally essential element, especially important in thyroid hormone synthesis. In solution, it has anti-infective properties and is used topically. [NIH] 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] Isoenzyme: Different forms of an enzyme, usually occurring in different tissues. The isoenzymes of a particular enzyme catalyze the same reaction but they differ in some of their properties. [NIH] Isolated limb perfusion: A technique that may be used to deliver anticancer drugs directly to an arm or leg. The flow of blood to and from the limb is temporarily stopped with a tourniquet, and anticancer drugs are put directly into the blood of the limb. This allows the person to receive a high dose of drugs in the area where the cancer occurred. [NIH] Isometric Contraction: Muscular contractions characterized by increase in tension without change in length. [NIH] Joint: The point of contact between elements of an animal skeleton with the parts that surround and support it. [NIH] Kb: A measure of the length of DNA fragments, 1 Kb = 1000 base pairs. The largest DNA fragments are up to 50 kilobases long. [NIH] Keratin: A class of fibrous proteins or scleroproteins important both as structural proteins and as keys to the study of protein conformation. The family represents the principal constituent of epidermis, hair, nails, horny tissues, and the organic matrix of tooth enamel. Two major conformational groups have been characterized, alpha-keratin, whose peptide backbone forms an alpha-helix, and beta-keratin, whose backbone forms a zigzag or pleated sheet structure. [NIH] Keratinocytes: Epidermal cells which synthesize keratin and undergo characteristic changes as they move upward from the basal layers of the epidermis to the cornified (horny) layer of the skin. Successive stages of differentiation of the keratinocytes forming the epidermal layers are basal cell, spinous or prickle cell, and the granular cell. [NIH]
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Keto: It consists of 8 carbon atoms and within the endotoxins, it connects poysaccharide and lipid A. [NIH] Kidney Disease: Any one of several chronic conditions that are caused by damage to the cells of the kidney. People who have had diabetes for a long time may have kidney damage. Also called nephropathy. [NIH] Kinetics: The study of rate dynamics in chemical or physical systems. [NIH] Labile: 1. Gliding; moving from point to point over the surface; unstable; fluctuating. 2. Chemically unstable. [EU] Lacrimal: Pertaining to the tears. [EU] Laminin: Large, noncollagenous glycoprotein with antigenic properties. It is localized in the basement membrane lamina lucida and functions to bind epithelial cells to the basement membrane. Evidence suggests that the protein plays a role in tumor invasion. [NIH] Language Development: The gradual expansion in complexity and meaning of symbols and sounds as perceived and interpreted by the individual through a maturational and learning process. Stages in development include babbling, cooing, word imitation with cognition, and use of short sentences. [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] 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] Leprosy: A chronic granulomatous infection caused by Mycobacterium leprae. The granulomatous lesions are manifested in the skin, the mucous membranes, and the peripheral nerves. Two polar or principal types are lepromatous and tuberculoid. [NIH] Lethal: Deadly, fatal. [EU] Leucine: An essential branched-chain amino acid important for hemoglobin formation. [NIH] 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] Library Services: Services offered to the library user. They include reference and circulation. [NIH]
Life Expectancy: A figure representing the number of years, based on known statistics, to which any person of a given age may reasonably expect to live. [NIH] Ligament: A band of fibrous tissue that connects bones or cartilages, serving to support and strengthen joints. [EU] Ligands: A RNA simulation method developed by the MIT. [NIH]
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Ligase: An enzyme that repairs single stranded discontinuities in double-stranded DNA molecules in the cell. Purified DNA ligase is used in gene cloning to join DNA molecules together. [NIH] Limb perfusion: A technique that may be used to deliver anticancer drugs directly to an arm or leg. The flow of blood to and from the limb is temporarily stopped with a tourniquet, and anticancer drugs are put directly into the blood of the limb. This allows the person to receive a high dose of drugs in the area where the cancer occurred. [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] Linkage Disequilibrium: Nonrandom association of linked genes. This is the tendency of the alleles of two separate but already linked loci to be found together more frequently than would be expected by chance alone. [NIH] Lipid: Fat. [NIH] Lipid Peroxidation: Peroxidase catalyzed oxidation of lipids using hydrogen peroxide as an electron acceptor. [NIH] Lipodystrophy: A collection of rare conditions resulting from defective fat metabolism and characterized by atrophy of the subcutaneous fat. They include total, congenital or acquired, partial, abdominal infantile, and localized lipodystrophy. [NIH] Lipoprotein: Any of the lipid-protein complexes in which lipids are transported in the blood; lipoprotein particles consist of a spherical hydrophobic core of triglycerides or cholesterol esters surrounded by an amphipathic monolayer of phospholipids, cholesterol, and apolipoproteins; the four principal classes are high-density, low-density, and very-lowdensity lipoproteins and chylomicrons. [EU] Liver: A large, glandular organ located in the upper abdomen. The liver cleanses the blood and aids in digestion by secreting bile. [NIH] Liver Regeneration: Repair or renewal of hepatic tissue. [NIH] Liver scan: An image of the liver created on a computer screen or on film. A radioactive substance is injected into a blood vessel and travels through the bloodstream. It collects in the liver, especially in abnormal areas, and can be detected by the scanner. [NIH] Lobe: A portion of an organ such as the liver, lung, breast, or brain. [NIH] Localization: The process of determining or marking the location or site of a lesion or disease. May also refer to the process of keeping a lesion or disease in a specific location or site. [NIH] Localized: Cancer which has not metastasized yet. [NIH] Locomotion: Movement or the ability to move from one place or another. It can refer to humans, vertebrate or invertebrate animals, and microorganisms. [NIH] Locomotor: Of or pertaining to locomotion; pertaining to or affecting the locomotive apparatus of the body. [EU] Longitudinal Studies: Studies in which variables relating to an individual or group of individuals are assessed over a period of time. [NIH] Longitudinal study: Also referred to as a "cohort study" or "prospective study"; the analytic method of epidemiologic study in which subsets of a defined population can be identified who are, have been, or in the future may be exposed or not exposed, or exposed in different degrees, to a factor or factors hypothesized to influence the probability of occurrence of a given disease or other outcome. The main feature of this type of study is to observe large
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numbers of subjects over an extended time, with comparisons of incidence rates in groups that differ in exposure levels. [NIH] Loop: A wire usually of platinum bent at one end into a small loop (usually 4 mm inside diameter) and used in transferring microorganisms. [NIH] Lucida: An instrument, invented by Wollaton, consisting essentially of a prism or a mirror through which an object can be viewed so as to appear on a plane surface seen in direct view and on which the outline of the object may be traced. [NIH] Luciferase: Any one of several enzymes that catalyze the bioluminescent reaction in certain marine crustaceans, fish, bacteria, and insects. The enzyme is a flavoprotein; it oxidizes luciferins to an electronically excited compound that emits energy in the form of light. The color of light emitted varies with the organism. The firefly enzyme is a valuable reagent for measurement of ATP concentration. (Dorland, 27th ed) EC 1.13.12.-. [NIH] Lumbar: Pertaining to the loins, the part of the back between the thorax and the pelvis. [EU] Lumen: The cavity or channel within a tube or tubular organ. [EU] Lupus: A form of cutaneous tuberculosis. It is seen predominantly in women and typically involves the nasal, buccal, and conjunctival mucosa. [NIH] 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] Lymphocyte: A white blood cell. Lymphocytes have a number of roles in the immune system, including the production of antibodies and other substances that fight infection and diseases. [NIH] Lymphoid: Referring to lymphocytes, a type of white blood cell. Also refers to tissue in which lymphocytes develop. [NIH] Lymphoma: A general term for various neoplastic diseases of the lymphoid tissue. [NIH] Lysosome: A sac-like compartment inside a cell that has enzymes that can break down cellular components that need to be destroyed. [NIH] Macrophage: A type of white blood cell that surrounds and kills microorganisms, removes dead cells, and stimulates the action of other immune system cells. [NIH] Macrophage Colony-Stimulating Factor: A mononuclear phagocyte colony-stimulating factor synthesized by mesenchymal cells. The compound stimulates the survival, proliferation, and differentiation of hematopoietic cells of the monocyte-macrophage series. M-CSF is a disulfide-bonded glycoprotein dimer with a MW of 70 kDa. It binds to a specific high affinity receptor (receptor, macrophage colony-stimulating factor). [NIH] Magnetic Resonance Imaging: Non-invasive method of demonstrating internal anatomy
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based on the principle that atomic nuclei in a strong magnetic field absorb pulses of radiofrequency energy and emit them as radiowaves which can be reconstructed into computerized images. The concept includes proton spin tomographic techniques. [NIH] Magnetic Resonance Spectroscopy: Spectroscopic method of measuring the magnetic moment of elementary particles such as atomic nuclei, protons or electrons. It is employed in clinical applications such as NMR Tomography (magnetic resonance imaging). [NIH] Magnetoencephalography: The measurement of magnetic fields over the head generated by electric currents in the brain. As in any electrical conductor, electric fields in the brain are accompanied by orthogonal magnetic fields. The measurement of these fields provides information about the localization of brain activity which is complementary to that provided by electroencephalography. Magnetoencephalography may be used alone or together with electroencephalography, for measurement of spontaneous or evoked activity, and for research or clinical purposes. [NIH] Malaria: A protozoan disease caused in humans by four species of the genus Plasmodium (P. falciparum (malaria, falciparum), P. vivax (malaria, vivax), P. ovale, and P. malariae) and transmitted by the bite of an infected female mosquito of the genus Anopheles. Malaria is endemic in parts of Asia, Africa, Central and South America, Oceania, and certain Caribbean islands. It is characterized by extreme exhaustion associated with paroxysms of high fever, sweating, shaking chills, and anemia. Malaria in animals is caused by other species of plasmodia. [NIH] Malaria, Falciparum: Malaria caused by Plasmodium falciparum. This is the severest form of malaria and is associated with the highest levels of parasites in the blood. This disease is characterized by irregularly recurring febrile paroxysms that in extreme cases occur with acute cerebral, renal, or gastrointestinal manifestations. [NIH] Malaria, Vivax: Malaria caused by Plasmodium vivax. This form of malaria is less severe than malaria, falciparum, but there is a higher probability for relapses to occur. Febrile paroxysms often occur every other day. [NIH] 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] Malignant tumor: A tumor capable of metastasizing. [NIH] Malnutrition: A condition caused by not eating enough food or not eating a balanced diet. [NIH]
Mammary: Pertaining to the mamma, or breast. [EU] Mammography: Radiographic examination of the breast. [NIH] Mandible: The largest and strongest bone of the face constituting the lower jaw. It supports the lower teeth. [NIH] Manifest: Being the part or aspect of a phenomenon that is directly observable : concretely expressed in behaviour. [EU] Masseter Muscle: A masticatory muscle whose action is closing the jaws. [NIH] Mastication: The act and process of chewing and grinding food in the mouth. [NIH] Masticatory: 1. subserving or pertaining to mastication; affecting the muscles of mastication. 2. a remedy to be chewed but not swallowed. [EU]
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Maxillary: Pertaining to the maxilla : the irregularly shaped bone that with its fellow forms the upper jaw. [EU] Mechanical ventilation: Use of a machine called a ventilator or respirator to improve the exchange of air between the lungs and the atmosphere. [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] Meiosis: A special method of cell division, occurring in maturation of the germ cells, by means of which each daughter nucleus receives half the number of chromosomes characteristic of the somatic cells of the species. [NIH] Melanin: The substance that gives the skin its color. [NIH] Membrane: A very thin layer of tissue that covers a surface. [NIH] Membrane Fluidity: The motion of phospholipid molecules within the lipid bilayer, dependent on the classes of phospholipids present, their fatty acid composition and degree of unsaturation of the acyl chains, the cholesterol concentration, and temperature. [NIH] Membrane Fusion: The adherence of cell membranes, intracellular membranes, or artifical membrane models of either to each other or to viruses, parasites, or interstitial particles through a variety of chemical and physical processes. [NIH] Membrane Glycoproteins: Glycoproteins found on the membrane or surface of cells. [NIH] Membrane Potentials: Ratio of inside versus outside concentration of potassium, sodium, chloride and other ions in diffusible tissues or cells. Also called transmembrane and resting potentials, they are measured by recording electrophysiologic responses in voltagedependent ionic channels of (e.g.) nerve, muscle and blood cells as well as artificial membranes. [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] Mental: Pertaining to the mind; psychic. 2. (L. mentum chin) pertaining to the chin. [EU] Mental deficiency: A condition of arrested or incomplete development of mind from inherent causes or induced by disease or injury. [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 Retardation: Refers to sub-average general intellectual functioning which originated during the developmental period and is associated with impairment in adaptive behavior. [NIH]
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Mesenchymal: Refers to cells that develop into connective tissue, blood vessels, and lymphatic tissue. [NIH] Mesoderm: The middle germ layer of the embryo. [NIH] Metabolic disorder: A condition in which normal metabolic processes are disrupted, usually because of a missing enzyme. [NIH] Metastasis: The spread of cancer from one part of the body to another. Tumors formed from cells that have spread are called "secondary tumors" and contain cells that are like those in the original (primary) tumor. The plural is metastases. [NIH] Metastatic: Having to do with metastasis, which is the spread of cancer from one part of the body to another. [NIH] Metastatic cancer: Cancer that has spread from the place in which it started to other parts of the body. [NIH] Methyltransferase: A drug-metabolizing enzyme. [NIH] MI: Myocardial infarction. Gross necrosis of the myocardium as a result of interruption of the blood supply to the area; it is almost always caused by atherosclerosis of the coronary arteries, upon which coronary thrombosis is usually superimposed. [NIH] Mice Minute Virus: The type species of parvovirus prevalent in mouse colonies and found as a contaminant of many transplanted tumors or leukemias. [NIH] Mice, Transgenic: Laboratory mice that have been produced from a genetically manipulated egg or embryo. The technique involves microinjection of DNA fragments from another species into the nucleus of the fertilized egg. [NIH] Microbe: An organism which cannot be observed with the naked eye; e. g. unicellular animals, lower algae, lower fungi, bacteria. [NIH] Microbiology: The study of microorganisms such as fungi, bacteria, algae, archaea, and viruses. [NIH] Microfilaments: The smallest of the cytoskeletal filaments. They are composed chiefly of actin. [NIH] Microglia: The third type of glial cell, along with astrocytes and oligodendrocytes (which together form the macroglia). Microglia vary in appearance depending on developmental stage, functional state, and anatomical location; subtype terms include ramified, perivascular, ameboid, resting, and activated. Microglia clearly are capable of phagocytosis and play an important role in a wide spectrum of neuropathologies. They have also been suggested to act in several other roles including in secretion (e.g., of cytokines and neural growth factors), in immunological processing (e.g., antigen presentation), and in central nervous system development and remodeling. [NIH] Microorganism: An organism that can be seen only through a microscope. Microorganisms include bacteria, protozoa, algae, and fungi. Although viruses are not considered living organisms, they are sometimes classified as microorganisms. [NIH] Microscopy: The application of microscope magnification to the study of materials that cannot be properly seen by the unaided eye. [NIH] Microtubule-Associated Proteins: High molecular weight proteins found in the microtubules of the cytoskeletal system. Under certain conditions they are required for tubulin assembly into the microtubules and stabilize the assembled microtubules. [NIH] Microtubules: Slender, cylindrical filaments found in the cytoskeleton of plant and animal cells. They are composed of the protein tubulin. [NIH] Midwifery: The practice of assisting women in childbirth. [NIH]
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Migration: The systematic movement of genes between populations of the same species, geographic race, or variety. [NIH] Milliliter: A measure of volume for a liquid. A milliliter is approximately 950-times smaller than a quart and 30-times smaller than a fluid ounce. A milliliter of liquid and a cubic centimeter (cc) of liquid are the same. [NIH] Mineralization: The action of mineralizing; the state of being mineralized. [EU] Mitochondria: Parts of a cell where aerobic production (also known as cell respiration) takes place. [NIH] Mitosis: A method of indirect cell division by means of which the two daughter nuclei normally receive identical complements of the number of chromosomes of the somatic cells of the species. [NIH] Mitotic: Cell resulting from mitosis. [NIH] Mobility: Capability of movement, of being moved, or of flowing freely. [EU] Modeling: A treatment procedure whereby the therapist presents the target behavior which the learner is to imitate and make part of his repertoire. [NIH] Modification: A change in an organism, or in a process in an organism, that is acquired from its own activity or environment. [NIH] Modulator: A specific inductor that brings out characteristics peculiar to a definite region. [EU]
Molecular: Of, pertaining to, or composed of molecules : a very small mass of matter. [EU] Molecular Chaperones: A family of cellular proteins that mediate the correct assembly or disassembly of other polypeptides, and in some cases their assembly into oligomeric structures, but which are not components of those final structures. It is believed that chaperone proteins assist polypeptides to self-assemble by inhibiting alternative assembly pathways that produce nonfunctional structures. Some classes of molecular chaperones are the nucleoplasmins, the chaperonins, the heat-shock proteins 70, and the heat-shock proteins 90. [NIH] Molecular Structure: The location of the atoms, groups or ions relative to one another in a molecule, as well as the number, type and location of covalent bonds. [NIH] Molecule: A chemical made up of two or more atoms. The atoms in a molecule can be the same (an oxygen molecule has two oxygen atoms) or different (a water molecule has two hydrogen atoms and one oxygen atom). Biological molecules, such as proteins and DNA, can be made up of many thousands of atoms. [NIH] Monitor: An apparatus which automatically records such physiological signs as respiration, pulse, and blood pressure in an anesthetized patient or one undergoing surgical or other procedures. [NIH] Monoclonal: An antibody produced by culturing a single type of cell. It therefore consists of a single species of immunoglobulin molecules. [NIH] Monoclonal antibodies: Laboratory-produced substances that can locate and bind to cancer cells wherever they are in the body. Many monoclonal antibodies are used in cancer detection or therapy; each one recognizes a different protein on certain cancer cells. Monoclonal antibodies can be used alone, or they can be used to deliver drugs, toxins, or radioactive material directly to a tumor. [NIH] Monocyte: A type of white blood cell. [NIH] Monogenic: A human disease caused by a mutation in a single gene. [NIH] Mononuclear: A cell with one nucleus. [NIH]
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Morphogenesis: The development of the form of an organ, part of the body, or organism. [NIH]
Morphological: Relating to the configuration or the structure of live organs. [NIH] Morphology: The science of the form and structure of organisms (plants, animals, and other forms of life). [NIH] Motility: The ability to move spontaneously. [EU] Motor Activity: The physical activity of an organism as a behavioral phenomenon. [NIH] Motor nerve: An efferent nerve conveying an impulse that excites muscular contraction. [NIH]
Motor Neurons: Neurons which activate muscle cells. [NIH] Motor Skills: Performance of complex motor acts. [NIH] Mucins: A secretion containing mucopolysaccharides and protein that is the chief constituent of mucus. [NIH] Mucosa: A mucous membrane, or tunica mucosa. [EU] Multiple sclerosis: A disorder of the central nervous system marked by weakness, numbness, a loss of muscle coordination, and problems with vision, speech, and bladder control. Multiple sclerosis is thought to be an autoimmune disease in which the body's immune system destroys myelin. Myelin is a substance that contains both protein and fat (lipid) and serves as a nerve insulator and helps in the transmission of nerve signals. [NIH] Muscle Contraction: A process leading to shortening and/or development of tension in muscle tissue. Muscle contraction occurs by a sliding filament mechanism whereby actin filaments slide inward among the myosin filaments. [NIH] Muscle Fibers: Large single cells, either cylindrical or prismatic in shape, that form the basic unit of muscle tissue. They consist of a soft contractile substance enclosed in a tubular sheath. [NIH] Muscle 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 Hypotonia: A diminution of the skeletal muscle tone marked by a diminished resistance to passive stretching. [NIH] Muscle Proteins: The protein constituents of muscle, the major ones being ACTINS and MYOSIN. More than a dozen accessary proteins exist including troponin, tropomyosin, and dystrophin. [NIH] Muscle relaxant: An agent that specifically aids in reducing muscle tension, as those acting at the polysynaptic neurons of motor nerves (e.g. meprobamate) or at the myoneural junction (curare and related compounds). [EU] Muscle Relaxation: That phase of a muscle twitch during which a muscle returns to a resting position. [NIH] Muscle tension: A force in a material tending to produce extension; the state of being stretched. [NIH] Muscular Atrophy: Derangement in size and number of muscle fibers occurring with aging, reduction in blood supply, or following immobilization, prolonged weightlessness, malnutrition, and particularly in denervation. [NIH] Muscular 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
Dictionary 407
characterized by progressive degeneration of skeletal muscles. [NIH] Musculature: The muscular apparatus of the body, or of any part of it. [EU] Musculoskeletal System: Themuscles, bones, and cartilage of the body. [NIH] Music Therapy: The use of music as an adjunctive therapy in the treatment of neurological, mental, or behavioral disorders. [NIH] Mutagenic: Inducing genetic mutation. [EU] Mutagens: Chemical agents that increase the rate of genetic mutation by interfering with the function of nucleic acids. A clastogen is a specific mutagen that causes breaks in chromosomes. [NIH] Mutate: To change the genetic material of a cell. Then changes (mutations) can be harmful, beneficial, or have no effect. [NIH] Myasthenia: Muscular debility; any constitutional anomaly of muscle. [EU] Myelin: The fatty substance that covers and protects nerves. [NIH] Myeloid Cells: Cells which include the monocytes and the granulocytes. [NIH] 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] Myogenic Regulatory Factors: A family of muscle-specific transcription factors which bind to DNA in control regions and thus regulate myogenesis. All members of this family contain a conserved helix-loop-helix motif which is homologous to the myc family proteins. These factors are only found in skeletal muscle. Members include the myoD protein, myogenin, myf-5, and myf-6 (also called MRF4 or herculin). [NIH] Myogenin: A myogenic regulatory factor that controls myogenesis. Myogenin is induced during differentiation of every skeletal muscle cell line that has been investigated, in contrast to the other myogenic regulatory factors that only appear in certain cell types. [NIH] Myoglobin: A conjugated protein which is the oxygen-transporting pigment of muscle. It is made up of one globin polypeptide chain and one heme group. [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] Myotonic Dystrophy: A condition presenting muscle weakness and wasting which may be progressive. [NIH] Naive: Used to describe an individual who has never taken a certain drug or class of drugs (e. g., AZT-naive, antiretroviral-naive), or to refer to an undifferentiated immune system cell. [NIH] Natural selection: A part of the evolutionary process resulting in the survival and reproduction of the best adapted individuals. [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
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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] 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] Needle biopsy: The removal of tissue or fluid with a needle for examination under a microscope. Also called fine-needle aspiration. [NIH] Neonatal: Pertaining to the first four weeks after birth. [EU] Neonatal period: The first 4 weeks after birth. [NIH] Neoplastic: Pertaining to or like a neoplasm (= any new and abnormal growth); pertaining to neoplasia (= the formation of a neoplasm). [EU] Nephropathy: Disease of the kidneys. [EU] Nerve: A cordlike structure of nervous tissue that connects parts of the nervous system with other tissues of the body and conveys nervous impulses to, or away from, these tissues. [NIH] Nerve Regeneration: Renewal or physiological repair of damaged nerve tissue. [NIH] Nervous System: The entire nerve apparatus composed of the brain, spinal cord, nerves and ganglia. [NIH] Networks: Pertaining to a nerve or to the nerves, a meshlike structure of interlocking fibers or strands. [NIH] Neural: 1. Pertaining to a nerve or to the nerves. 2. Situated in the region of the spinal axis, as the neutral arch. [EU] 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] 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] 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] Neuromuscular: Pertaining to muscles and nerves. [EU] Neuromuscular Blocking Agents: Drugs that interrupt transmission of nerve impulses at the skeletal neuromuscular junction. They can be of two types, competitive, stabilizing blockers (neuromuscular nondepolarizing agents) or noncompetitive, depolarizing agents (neuromuscular depolarizing agents). Both prevent acetylcholine from triggering the muscle contraction and they are used as anesthesia adjuvants, as relaxants during electroshock, in convulsive states, etc. [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]
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Neuromuscular Junction: The synapse between a neuron and a muscle. [NIH] Neuronal: Pertaining to a neuron or neurons (= conducting cells of the nervous system). [EU] Neurons: The basic cellular units of nervous tissue. Each neuron consists of a body, an axon, and dendrites. Their purpose is to receive, conduct, and transmit impulses in the nervous system. [NIH] Neuropathy: A problem in any part of the nervous system except the brain and spinal cord. Neuropathies can be caused by infection, toxic substances, or disease. [NIH] Neuropeptides: Peptides released by neurons as intercellular messengers. Many neuropeptides are also hormones released by non-neuronal cells. [NIH] Neurophysiology: The scientific discipline concerned with the physiology of the nervous system. [NIH] Neurosciences: The scientific disciplines concerned with the embryology, anatomy, physiology, biochemistry, pharmacology, etc., of the nervous sytem. [NIH] Neurotoxic: Poisonous or destructive to nerve tissue. [EU] Neurotransmitter: Any of a group of substances that are released on excitation from the axon terminal of a presynaptic neuron of the central or peripheral nervous system and travel across the synaptic cleft to either excite or inhibit the target cell. Among the many substances that have the properties of a neurotransmitter are acetylcholine, norepinephrine, epinephrine, dopamine, glycine, y-aminobutyrate, glutamic acid, substance P, enkephalins, endorphins, and serotonin. [EU] Neutrons: Electrically neutral elementary particles found in all atomic nuclei except light hydrogen; the mass is equal to that of the proton and electron combined and they are unstable when isolated from the nucleus, undergoing beta decay. Slow, thermal, epithermal, and fast neutrons refer to the energy levels with which the neutrons are ejected from heavier nuclei during their decay. [NIH] 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] Nitric Oxide: A free radical gas produced endogenously by a variety of mammalian cells. It is synthesized from arginine by a complex reaction, catalyzed by nitric oxide synthase. Nitric oxide is endothelium-derived relaxing factor. It is released by the vascular endothelium and mediates the relaxation induced by some vasodilators such as acetylcholine and bradykinin. It also inhibits platelet aggregation, induces disaggregation of aggregated platelets, and inhibits platelet adhesion to the vascular endothelium. Nitric oxide activates cytosolic guanylate cyclase and thus elevates intracellular levels of cyclic GMP. [NIH]
Nitrogen: An element with the atomic symbol N, atomic number 7, and atomic weight 14. Nitrogen exists as a diatomic gas and makes up about 78% of the earth's atmosphere by volume. It is a constituent of proteins and nucleic acids and found in all living cells. [NIH] Nuclear: A test of the structure, blood flow, and function of the kidneys. The doctor injects a mildly radioactive solution into an arm vein and uses x-rays to monitor its progress through the kidneys. [NIH] Nuclear Envelope: The membrane system of the cell nucleus that surrounds the nucleoplasm. It consists of two concentric membranes separated by the perinuclear space. The structures of the envelope where it opens to the cytoplasm are called the nuclear pores (nuclear pore). [NIH] Nuclear Pore: An opening through the nuclear envelope formed by the nuclear pore
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complex which transports nuclear proteins or RNA into or out of the cell nucleus and which, under some conditions, acts as an ion channel. [NIH] Nuclear Proteins: Proteins found in the nucleus of a cell. Do not confuse with nucleoproteins which are proteins conjugated with nucleic acids, that are not necessarily present in the nucleus. [NIH] Nuclei: A body of specialized protoplasm found in nearly all cells and containing the chromosomes. [NIH] Nucleic acid: Either of two types of macromolecule (DNA or RNA) formed by polymerization of nucleotides. Nucleic acids are found in all living cells and contain the information (genetic code) for the transfer of genetic information from one generation to the next. [NIH] Nucleic Acid Hybridization: The process whereby two single-stranded polynucleotides form a double-stranded molecule, with hydrogen bonding between the complementary bases in the two strains. [NIH] Nucleic Acid Probes: Nucleic acid which complements a specific mRNA or DNA molecule, or fragment thereof; used for hybridization studies in order to identify microorganisms and for genetic studies. [NIH] Nucleoproteins: Proteins conjugated with nucleic acids. [NIH] Nucleus: A body of specialized protoplasm found in nearly all cells and containing the chromosomes. [NIH] Nursing Staff: Personnel who provide nursing service to patients in an organized facility, institution, or agency. [NIH] Nutritional Support: The administration of nutrients for assimilation and utilization by a patient by means other than normal eating. It does not include fluid therapy which normalizes body fluids to restore water-electrolyte balance. [NIH] Obsessive-Compulsive Disorder: An anxiety disorder characterized by recurrent, persistent obsessions or compulsions. Obsessions are the intrusive ideas, thoughts, or images that are experienced as senseless or repugnant. Compulsions are repetitive and seemingly purposeful behavior which the individual generally recognizes as senseless and from which the individual does not derive pleasure although it may provide a release from tension. [NIH] Occupational Therapy: The field concerned with utilizing craft or work activities in the rehabilitation of patients. Occupational therapy can also refer to the activities themselves. [NIH]
Ocular: 1. Of, pertaining to, or affecting the eye. 2. Eyepiece. [EU] Ointments: Semisolid preparations used topically for protective emollient effects or as a vehicle for local administration of medications. Ointment bases are various mixtures of fats, waxes, animal and plant oils and solid and liquid hydrocarbons. [NIH] Oncogene: A gene that normally directs cell growth. If altered, an oncogene can promote or allow the uncontrolled growth of cancer. Alterations can be inherited or caused by an environmental exposure to carcinogens. [NIH] Oncogenic: Chemical, viral, radioactive or other agent that causes cancer; carcinogenic. [NIH] Oncology: The study of cancer. [NIH] On-line: A sexually-reproducing population derived from a common parentage. [NIH] Oogenesis: The formation, development, and maturation of the female germ cell. [NIH] Opacity: Degree of density (area most dense taken for reading). [NIH]
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Operon: The genetic unit consisting of a feedback system under the control of an operator gene, in which a structural gene transcribes its message in the form of mRNA upon blockade of a repressor produced by a regulator gene. Included here is the attenuator site of bacterial operons where transcription termination is regulated. [NIH] Ophthalmology: A surgical specialty concerned with the structure and function of the eye and the medical and surgical treatment of its defects and diseases. [NIH] 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] Opsin: A protein formed, together with retinene, by the chemical breakdown of metarhodopsin. [NIH] Optic Nerve: The 2nd cranial nerve. The optic nerve conveys visual information from the retina to the brain. The nerve carries the axons of the retinal ganglion cells which sort at the optic chiasm and continue via the optic tracts to the brain. The largest projection is to the lateral geniculate nuclei; other important targets include the superior colliculi and the suprachiasmatic nuclei. Though known as the second cranial nerve, it is considered part of the central nervous system. [NIH] 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] Organ Culture: The growth in aseptic culture of plant organs such as roots or shoots, beginning with organ primordia or segments and maintaining the characteristics of the organ. [NIH] Organelles: Specific particles of membrane-bound organized living substances present in eukaryotic cells, such as the mitochondria; the golgi apparatus; endoplasmic reticulum; lysomomes; plastids; and vacuoles. [NIH] Ori region: The point or region (origin) at which DNA replication begins in a bacterium or virus. Plasmids used in rec DNA research always contain an ori region, which gives very efficient initiation of replication. [NIH] Orofacial: Of or relating to the mouth and face. [EU] Orthopaedic: Pertaining to the correction of deformities of the musculoskeletal system; pertaining to orthopaedics. [EU] Osmosis: Tendency of fluids (e.g., water) to move from the less concentrated to the more concentrated side of a semipermeable membrane. [NIH] Osmotic: Pertaining to or of the nature of osmosis (= the passage of pure solvent from a solution of lesser to one of greater solute concentration when the two solutions are separated by a membrane which selectively prevents the passage of solute molecules, but is permeable to the solvent). [EU] Ossicles: The hammer, anvil and stirrup, the small bones of the middle ear, which transmit the vibrations from the tympanic membrane to the oval window. [NIH] Ossification: The formation of bone or of a bony substance; the conversion of fibrous tissue or of cartilage into bone or a bony substance. [EU] Osteoarthritis: A progressive, degenerative joint disease, the most common form of arthritis, especially in older persons. The disease is thought to result not from the aging process but from biochemical changes and biomechanical stresses affecting articular cartilage. In the foreign literature it is often called osteoarthrosis deformans. [NIH] Osteoclasts: A large multinuclear cell associated with the absorption and removal of bone.
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An odontoclast, also called cementoclast, is cytomorphologically the same as an osteoclast and is involved in cementum resorption. [NIH] Osteogenesis: The histogenesis of bone including ossification. It occurs continuously but particularly in the embryo and child and during fracture repair. [NIH] Osteoporosis: Reduction of bone mass without alteration in the composition of bone, leading to fractures. Primary osteoporosis can be of two major types: postmenopausal osteoporosis and age-related (or senile) osteoporosis. [NIH] Ostomy: Surgical construction of an artificial opening (stoma) for external fistulization of a duct or vessel by insertion of a tube with or without a supportive stent. [NIH] Ovaries: The pair of female reproductive glands in which the ova, or eggs, are formed. The ovaries are located in the pelvis, one on each side of the uterus. [NIH] Ovulation: The discharge of a secondary oocyte from a ruptured graafian follicle. [NIH] Ovum: A female germ cell extruded from the ovary at ovulation. [NIH] Ovum Implantation: Endometrial implantation of the blastocyst. [NIH] Oxandrolone: A synthetic hormone with anabolic and androgenic properties. [NIH] Oxidation: The act of oxidizing or state of being oxidized. Chemically it consists in the increase of positive charges on an atom or the loss of negative charges. Most biological oxidations are accomplished by the removal of a pair of hydrogen atoms (dehydrogenation) from a molecule. Such oxidations must be accompanied by reduction of an acceptor molecule. Univalent o. indicates loss of one electron; divalent o., the loss of two electrons. [EU]
Oxidative Phosphorylation: Electron transfer through the cytochrome system liberating free energy which is transformed into high-energy phosphate bonds. [NIH] Oxidative Stress: A disturbance in the prooxidant-antioxidant balance in favor of the former, leading to potential damage. Indicators of oxidative stress include damaged DNA bases, protein oxidation products, and lipid peroxidation products (Sies, Oxidative Stress, 1991, pxv-xvi). [NIH] Oxygen Consumption: The oxygen consumption is determined by calculating the difference between the amount of oxygen inhaled and exhaled. [NIH] Oxygenation: The process of supplying, treating, or mixing with oxygen. No:1245 oxygenation the process of supplying, treating, or mixing with oxygen. [EU] Pacemaker: An object or substance that influences the rate at which a certain phenomenon occurs; often used alone to indicate the natural cardiac pacemaker or an artificial cardiac pacemaker. In biochemistry, a substance whose rate of reaction sets the pace for a series of interrelated reactions. [EU] 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] 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]
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Paneth Cells: Epithelial cells found in the basal part of the intestinal glands (crypts of Lieberkuhn). Paneth cells synthesize and secrete lysozyme and cryptdins. [NIH] Paraffin: A mixture of solid hydrocarbons obtained from petroleum. It has a wide range of uses including as a stiffening agent in ointments, as a lubricant, and as a topical antiinflammatory. It is also commonly used as an embedding material in histology. [NIH] Paralysis: Loss of ability to move all or part of the body. [NIH] Paraparesis: Mild to moderate loss of bilateral lower extremity motor function, which may be a manifestation of spinal cord diseases; peripheral nervous system diseases; muscular diseases; intracranial hypertension; parasagittal brain lesions; and other conditions. [NIH] Paraplegia: Severe or complete loss of motor function in the lower extremities and lower portions of the trunk. This condition is most often associated with spinal cord diseases, although brain diseases; peripheral nervous system diseases; neuromuscular diseases; and muscular diseases may also cause bilateral leg weakness. [NIH] Paresthesia: Subjective cutaneous sensations (e.g., cold, warmth, tingling, pressure, etc.) that are experienced spontaneously in the absence of stimulation. [NIH] Parturition: The act or process of given birth to a child. [EU] Parvovirus: A genus of the family Parvoviridae, subfamily Parvovirinae, infecting a variety of vertebrates including humans. Parvoviruses are responsible for a number of important diseases but also can be non-pathogenic in certain hosts. The type species is mice minute virus. [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] Pathologies: The study of abnormality, especially the study of diseases. [NIH] Pathologist: A doctor who identifies diseases by studying cells and tissues under a microscope. [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]
Pedigree: A record of one's ancestors, offspring, siblings, and their offspring that may be used to determine the pattern of certain genes or disease inheritance within a family. [NIH] Pelvic: Pertaining to the pelvis. [EU] Pelvis: The lower part of the abdomen, located between the hip bones. [NIH] Pemphigus: Group of chronic blistering diseases characterized histologically by acantholysis and blister formation within the epidermis. [NIH] Penicillamine: 3-Mercapto-D-valine. The most characteristic degradation product of the
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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] 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]
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 Vascular Disease: Disease in the large blood vessels of the arms, legs, and feet. People who have had diabetes for a long time may get this because major blood vessels in their arms, legs, and feet are blocked and these limbs do not receive enough blood. The signs of PVD are aching pains in the arms, legs, and feet (especially when walking) and foot sores that heal slowly. Although people with diabetes cannot always avoid PVD, doctors say they have a better chance of avoiding it if they take good care of their feet, do not smoke, and keep both their blood pressure and diabetes under good control. [NIH] Peritoneal: Having to do with the peritoneum (the tissue that lines the abdominal wall and covers most of the organs in the abdomen). [NIH] Peritoneal Cavity: The space enclosed by the peritoneum. It is divided into two portions, the greater sac and the lesser sac or omental bursa, which lies behind the stomach. The two sacs are connected by the foramen of Winslow, or epiploic foramen. [NIH] Petrolatum: A colloidal system of semisolid hydrocarbons obtained from petroleum. It is used as an ointment base, topical protectant, and lubricant. [NIH] Petroleum: Naturally occurring complex liquid hydrocarbons which, after distillation, yield
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combustible fuels, petrochemicals, and lubricants. [NIH] PH: The symbol relating the hydrogen ion (H+) concentration or activity of a solution to that of a given standard solution. Numerically the pH is approximately equal to the negative logarithm of H+ concentration expressed in molarity. pH 7 is neutral; above it alkalinity increases and below it acidity increases. [EU] Phagocyte: An immune system cell that can surround and kill microorganisms and remove dead cells. Phagocytes include macrophages. [NIH] Phallic: Pertaining to the phallus, or penis. [EU] Pharmacologic: Pertaining to pharmacology or to the properties and reactions of drugs. [EU] Pharynx: The hollow tube about 5 inches long that starts behind the nose and ends at the top of the trachea (windpipe) and esophagus (the tube that goes to the stomach). [NIH] Phenolphthalein: An acid-base indicator which is colorless in acid solution, but turns pink to red as the solution becomes alkaline. It is used medicinally as a cathartic. [NIH] Phenotype: The outward appearance of the individual. It is the product of interactions between genes and between the genotype and the environment. This includes the killer phenotype, characteristic of yeasts. [NIH] Phenylalanine: An aromatic amino acid that is essential in the animal diet. It is a precursor of melanin, dopamine, noradrenalin, and thyroxine. [NIH] Pheromone: A substance secreted externally by certain animal species, especially insects, to affect the behavior or development of other members of the species. [NIH] Phospholipases: A class of enzymes that catalyze the hydrolysis of phosphoglycerides or glycerophosphatidates. EC 3.1.-. [NIH] Phospholipids: Lipids containing one or more phosphate groups, particularly those derived from either glycerol (phosphoglycerides; glycerophospholipids) or sphingosine (sphingolipids). They are polar lipids that are of great importance for the structure and function of cell membranes and are the most abundant of membrane lipids, although not stored in large amounts in the system. [NIH] Phosphorus: A non-metallic element that is found in the blood, muscles, nevers, bones, and teeth, and is a component of adenosine triphosphate (ATP; the primary energy source for the body's cells.) [NIH] Phosphorylase: An enzyme of the transferase class that catalyzes the phosphorylysis of a terminal alpha-1,4-glycosidic bond at the non-reducing end of a glycogen molecule, releasing a glucose 1-phosphate residue. Phosphorylase should be qualified by the natural substance acted upon. EC 2.4.1.1. [NIH] Phosphorylated: Attached to a phosphate group. [NIH] Phosphorylation: The introduction of a phosphoryl group into a compound through the formation of an ester bond between the compound and a phosphorus moiety. [NIH] Photoreceptor: Receptor capable of being activated by light stimuli, as a rod or cone cell of the eye. [NIH] Physical Therapy: The restoration of function and the prevention of disability following disease or injury with the use of light, heat, cold, water, electricity, ultrasound, and exercise. [NIH]
Physiologic: Having to do with the functions of the body. When used in the phrase "physiologic age," it refers to an age assigned by general health, as opposed to calendar age. [NIH]
Physiology: The science that deals with the life processes and functions of organismus, their
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cells, tissues, and organs. [NIH] Pigments: Any normal or abnormal coloring matter in plants, animals, or micro-organisms. [NIH]
Pilot study: The initial study examining a new method or treatment. [NIH] Pituitary Gland: A small, unpaired gland situated in the sella turcica tissue. It is connected to the hypothalamus by a short stalk. [NIH] Placenta: A highly vascular fetal organ through which the fetus absorbs oxygen and other nutrients and excretes carbon dioxide and other wastes. It begins to form about the eighth day of gestation when the blastocyst adheres to the decidua. [NIH] 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] 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] Plasmid: An autonomously replicating, extra-chromosomal DNA molecule found in many bacteria. Plasmids are widely used as carriers of cloned genes. [NIH] Plasticity: In an individual or a population, the capacity for adaptation: a) through gene changes (genetic plasticity) or b) through internal physiological modifications in response to changes of environment (physiological plasticity). [NIH] Plastids: Self-replicating cytoplasmic organelles of plant and algal cells that contain pigments and may synthesize and accumulate various substances. Plastids are used in phylogenetic studies. [NIH] Platelet Activation: A series of progressive, overlapping events triggered by exposure of the platelets to subendothelial tissue. These events include shape change, adhesiveness, aggregation, and release reactions. When carried through to completion, these events lead to the formation of a stable hemostatic plug. [NIH] Platelet Aggregation: The attachment of platelets to one another. This clumping together can be induced by a number of agents (e.g., thrombin, collagen) and is part of the mechanism leading to the formation of a thrombus. [NIH] Platelet-Derived Growth Factor: Mitogenic peptide growth hormone carried in the alphagranules of platelets. It is released when platelets adhere to traumatized tissues. Connective tissue cells near the traumatized region respond by initiating the process of replication. [NIH] Platelets: A type of blood cell that helps prevent bleeding by causing blood clots to form. Also called thrombocytes. [NIH] Platinum: Platinum. A heavy, soft, whitish metal, resembling tin, atomic number 78, atomic weight 195.09, symbol Pt. (From Dorland, 28th ed) It is used in manufacturing equipment for laboratory and industrial use. It occurs as a black powder (platinum black) and as a spongy substance (spongy platinum) and may have been known in Pliny's time as "alutiae". [NIH]
Pleated: Particular three-dimensional pattern of amyloidoses. [NIH] Pneumonia: Inflammation of the lungs. [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]
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Poliomyelitis: An acute viral disease, occurring sporadically and in epidemics, and characterized clinically by fever, sore throat, headache, and vomiting, often with stiffness of the neck and back. In the minor illness these may be the only symptoms. The major illness, which may or may not be preceded by the minor illness, is characterized by involvement of the central nervous system, stiff neck, pleocytosis in the spinal fluid, and perhaps paralysis. There may be subsequent atrophy of groups of muscles, ending in contraction and permanent deformity. The major illness is called acute anterior p., infantile paralysis and Heine-Medin disease. The disease is now largely controlled by vaccines. [EU] Polycystic: An inherited disorder characterized by many grape-like clusters of fluid-filled cysts that make both kidneys larger over time. These cysts take over and destroy working kidney tissue. PKD may cause chronic renal failure and end-stage renal disease. [NIH] Polymerase: An enzyme which catalyses the synthesis of DNA using a single DNA strand as a template. The polymerase copies the template in the 5'-3'direction provided that sufficient quantities of free nucleotides, dATP and dTTP are present. [NIH] Polymerase Chain Reaction: In vitro method for producing large amounts of specific DNA or RNA fragments of defined length and sequence from small amounts of short oligonucleotide flanking sequences (primers). The essential steps include thermal denaturation of the double-stranded target molecules, annealing of the primers to their complementary sequences, and extension of the annealed primers by enzymatic synthesis with DNA polymerase. The reaction is efficient, specific, and extremely sensitive. Uses for the reaction include disease diagnosis, detection of difficult-to-isolate pathogens, mutation analysis, genetic testing, DNA sequencing, and analyzing evolutionary relationships. [NIH] Polymers: Compounds formed by the joining of smaller, usually repeating, units linked by covalent bonds. These compounds often form large macromolecules (e.g., polypeptides, proteins, plastics). [NIH] Polymorphic: Occurring in several or many forms; appearing in different forms at different stages of development. [EU] Polymorphism: The occurrence together of two or more distinct forms in the same population. [NIH] Polysaccharide: A type of carbohydrate. It contains sugar molecules that are linked together chemically. [NIH] Port: An implanted device through which blood may be withdrawn and drugs may be infused without repeated needle sticks. Also called a port-a-cath. [NIH] Port-a-cath: An implanted device through which blood may be withdrawn and drugs may be infused without repeated needle sticks. Also called a port. [NIH] Posterior: Situated in back of, or in the back part of, or affecting the back or dorsal surface of the body. In lower animals, it refers to the caudal end of the body. [EU] Postmenopausal: Refers to the time after menopause. Menopause is the time in a woman's life when menstrual periods stop permanently; also called "change of life." [NIH] Postnatal: Occurring after birth, with reference to the newborn. [EU] Postsynaptic: Nerve potential generated by an inhibitory hyperpolarizing stimulation. [NIH] Post-synaptic: Nerve potential generated by an inhibitory hyperpolarizing stimulation. [NIH] Post-translational: The cleavage of signal sequence that directs the passage of the protein through a cell or organelle membrane. [NIH] Potassium: An element that is in the alkali group of metals. It has an atomic symbol K, atomic number 19, and atomic weight 39.10. It is the chief cation in the intracellular fluid of
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muscle and other cells. Potassium ion is a strong electrolyte and it plays a significant role in the regulation of fluid volume and maintenance of the water-electrolyte balance. [NIH] Potassium Channels: Cell membrane glycoproteins selective for potassium ions. [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] Practice Management: Business management of medical and dental practices that may include capital financing, utilization management, and arrangement of capitation agreements with other parties. [NIH] Preclinical: Before a disease becomes clinically recognizable. [EU] Precursor: Something that precedes. In biological processes, a substance from which another, usually more active or mature substance is formed. In clinical medicine, a sign or symptom that heralds another. [EU] 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] Prenatal: Existing or occurring before birth, with reference to the fetus. [EU] Pressoreceptors: Receptors in the vascular system, particularly the aorta and carotid sinus, which are sensitive to stretch of the vessel walls. [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] Prickle: Several layers of the epidermis where the individual cells are connected by cell bridges. [NIH] Prion: Small proteinaceous infectious particles that resist inactivation by procedures modifying nucleic acids and contain an abnormal isoform of a cellular protein which is a major and necessary component. [NIH] Probe: An instrument used in exploring cavities, or in the detection and dilatation of strictures, or in demonstrating the potency of channels; an elongated instrument for exploring or sounding body cavities. [NIH] Progeny: The offspring produced in any generation. [NIH] Progeria: An abnormal congenital condition characterized by premature aging in children, where all the changes of cell senescence occur. It is manifested by premature greying, hair loss, hearing loss, cataracts, arthritis,osteoporosis, diabetes mellitus, atrophy of subcutaneous fat, skeletal hypoplasia, and accelerated atherosclerosis. Many affected individuals develop malignant tumors, especially sarcomas. [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
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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] Progressive disease: Cancer that is increasing in scope or severity. [NIH] Proline: A non-essential amino acid that is synthesized from glutamic acid. It is an essential component of collagen and is important for proper functioning of joints and tendons. [NIH] Promoter: A chemical substance that increases the activity of a carcinogenic process. [NIH] Promotor: In an operon, a nucleotide sequence located at the operator end which contains all the signals for the correct initiation of genetic transcription by the RNA polymerase holoenzyme and determines the maximal rate of RNA synthesis. [NIH] Prone: Having the front portion of the body downwards. [NIH] Prone Position: The posture of an individual lying face down. [NIH] Prophase: The first phase of cell division, in which the chromosomes become visible, the nucleus starts to lose its identity, the spindle appears, and the centrioles migrate toward opposite poles. [NIH] Prophylaxis: An attempt to prevent disease. [NIH] Prospective study: An epidemiologic study in which a group of individuals (a cohort), all free of a particular disease and varying in their exposure to a possible risk factor, is followed over a specific amount of time to determine the incidence rates of the disease in the exposed and unexposed groups. [NIH] Prostate: A gland in males that surrounds the neck of the bladder and the urethra. It secretes a substance that liquifies coagulated semen. It is situated in the pelvic cavity behind the lower part of the pubic symphysis, above the deep layer of the triangular ligament, and rests upon the rectum. [NIH] Protease: Proteinase (= any enzyme that catalyses the splitting of interior peptide bonds in a protein). [EU] Protein Binding: The process in which substances, either endogenous or exogenous, bind to proteins, peptides, enzymes, protein precursors, or allied compounds. Specific proteinbinding measures are often used as assays in diagnostic assessments. [NIH] Protein C: A vitamin-K dependent zymogen present in the blood, which, upon activation by thrombin and thrombomodulin exerts anticoagulant properties by inactivating factors Va and VIIIa at the rate-limiting steps of thrombin formation. [NIH] Protein Conformation: The characteristic 3-dimensional shape of a protein, including the secondary, supersecondary (motifs), tertiary (domains) and quaternary structure of the peptide chain. Quaternary protein structure describes the conformation assumed by multimeric proteins (aggregates of more than one polypeptide chain). [NIH] Protein Folding: A rapid biochemical reaction involved in the formation of proteins. It begins even before a protein has been completely synthesized and proceeds through discrete intermediates (primary, secondary, and tertiary structures) before the final structure (quaternary structure) is developed. [NIH] Protein Isoforms: Different forms of a protein that may be produced from different genes, or from the same gene by alternative splicing. [NIH] Protein Kinases: A family of enzymes that catalyze the conversion of ATP and a protein to ADP and a phosphoprotein. EC 2.7.1.37. [NIH]
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Protein S: The vitamin K-dependent cofactor of activated protein C. Together with protein C, it inhibits the action of factors VIIIa and Va. A deficiency in protein S can lead to recurrent venous and arterial thrombosis. [NIH] Proteins: Polymers of amino acids linked by peptide bonds. The specific sequence of amino acids determines the shape and function of the protein. [NIH] Proteoglycan: A molecule that contains both protein and glycosaminoglycans, which are a type of polysaccharide. Proteoglycans are found in cartilage and other connective tissues. [NIH]
Proteolytic: 1. Pertaining to, characterized by, or promoting proteolysis. 2. An enzyme that promotes proteolysis (= the splitting of proteins by hydrolysis of the peptide bonds with formation of smaller polypeptides). [EU] 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] Protozoan: 1. Any individual of the protozoa; protozoon. 2. Of or pertaining to the protozoa; protozoal. [EU] Proximal: Nearest; closer to any point of reference; opposed to distal. [EU] Pseudogenes: Genes bearing close resemblance to known genes at different loci, but rendered non-functional by additions or deletions in structure that prevent normal transcription or translation. When lacking introns and containing a poly-A segment near the downstream end (as a result of reverse copying from processed nuclear RNA into doublestranded DNA), they are called processed genes. [NIH] Psychiatry: The medical science that deals with the origin, diagnosis, prevention, and treatment of mental disorders. [NIH] Psychic: Pertaining to the psyche or to the mind; mental. [EU] Psychoactive: Those drugs which alter sensation, mood, consciousness or other psychological or behavioral functions. [NIH] Psychological Tests: Standardized tests designed to measure abilities, as in intelligence, aptitude, and achievement tests, or to evaluate personality traits. [NIH] 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] Public Policy: A course or method of action selected, usually by a government, from among alternatives to guide and determine present and future decisions. [NIH] Pulmonary: Relating to the lungs. [NIH] Pulmonary Alveoli: Small polyhedral outpouchings along the walls of the alveolar sacs, alveolar ducts and terminal bronchioles through the walls of which gas exchange between alveolar air and pulmonary capillary blood takes place. [NIH] Pulmonary Artery: The short wide vessel arising from the conus arteriosus of the right ventricle and conveying unaerated blood to the lungs. [NIH]
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Pulmonary Valve: A valve situated at the entrance to the pulmonary trunk from the right ventricle. [NIH] Pulsation: A throb or rhythmical beat, as of the heart. [EU] 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]
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] Pustular: Pertaining to or of the nature of a pustule; consisting of pustules (= a visible collection of pus within or beneath the epidermis). [EU] Pyrimidines: A family of 6-membered heterocyclic compounds occurring in nature in a wide variety of forms. They include several nucleic acid constituents (cytosine, thymine, and uracil) and form the basic structure of the barbiturates. [NIH] 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] Quaternary: 1. Fourth in order. 2. Containing four elements or groups. [EU] Quiescent: Marked by a state of inactivity or repose. [EU] Race: A population within a species which exhibits general similarities within itself, but is both discontinuous and distinct from other populations of that species, though not sufficiently so as to achieve the status of a taxon. [NIH] Racemic: Optically inactive but resolvable in the way of all racemic compounds. [NIH] Radiation: Emission or propagation of electromagnetic energy (waves/rays), or the waves/rays themselves; a stream of electromagnetic particles (electrons, neutrons, protons, alpha particles) or a mixture of these. The most common source is the sun. [NIH] Radiation therapy: The use of high-energy radiation from x-rays, gamma rays, neutrons, and other sources to kill cancer cells and shrink tumors. Radiation may come from a machine outside the body (external-beam radiation therapy), or it may come from radioactive material placed in the body in the area near cancer cells (internal radiation therapy, implant radiation, or brachytherapy). Systemic radiation therapy uses a radioactive substance, such as a radiolabeled monoclonal antibody, that circulates throughout the body. Also called radiotherapy. [NIH] Radioactive: Giving off radiation. [NIH] Radiolabeled: Any compound that has been joined with a radioactive substance. [NIH] Radiological: Pertaining to radiodiagnostic and radiotherapeutic procedures, and interventional radiology or other planning and guiding medical radiology. [NIH] Radiotherapy: The use of ionizing radiation to treat malignant neoplasms and other benign conditions. The most common forms of ionizing radiation used as therapy are x-rays,
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gamma rays, and electrons. A special form of radiotherapy, targeted radiotherapy, links a cytotoxic radionuclide to a molecule that targets the tumor. When this molecule is an antibody or other immunologic molecule, the technique is called radioimmunotherapy. [NIH] Randomized: Describes an experiment or clinical trial in which animal or human subjects are assigned by chance to separate groups that compare different treatments. [NIH] 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] Recessive gene: A gene that is phenotypically expressed only when homozygous. [NIH] Recombinant: A cell or an individual with a new combination of genes not found together in either parent; usually applied to linked genes. [EU] Recombinant Proteins: Proteins prepared by recombinant DNA technology. [NIH] Recombination: The formation of new combinations of genes as a result of segregation in crosses between genetically different parents; also the rearrangement of linked genes due to crossing-over. [NIH] Rectum: The last 8 to 10 inches of the large intestine. [NIH] 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] Reentry: Reexcitation caused by continuous propagation of the same impulse for one or more cycles. [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] Refraction: A test to determine the best eyeglasses or contact lenses to correct a refractive error (myopia, hyperopia, or astigmatism). [NIH] Refractory: Not readily yielding to treatment. [EU] Regeneration: The natural renewal of a structure, as of a lost tissue or part. [EU] Regimen: A treatment plan that specifies the dosage, the schedule, and the duration of treatment. [NIH] Relaxant: 1. Lessening or reducing tension. 2. An agent that lessens tension. [EU] Remission: A decrease in or disappearance of signs and symptoms of cancer. In partial remission, some, but not all, signs and symptoms of cancer have disappeared. In complete remission, all signs and symptoms of cancer have disappeared, although there still may be cancer in the body. [NIH] Replication Origin: The point or region (origin) at which DNA replication begins in a bacterium or virus. Plasmids used in rec DNA research always contain an ori region, which gives very efficient initiation of replication. [NIH] Repressor: Any of the specific allosteric protein molecules, products of regulator genes, which bind to the operator of operons and prevent RNA polymerase from proceeding into
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the operon to transcribe messenger RNA. [NIH] Reproductive cells: Egg and sperm cells. Each mature reproductive cell carries a single set of 23 chromosomes. [NIH] Resolving: The ability of the eye or of a lens to make small objects that are close together, separately visible; thus revealing the structure of an object. [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 distress syndrome: A lung disease that occurs primarily in premature infants; the newborn must struggle for each breath and blueing of its skin reflects the baby's inability to get enough oxygen. [NIH] Respiratory failure: Inability of the lungs to conduct gas exchange. [NIH] 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 Physiology: Functions and activities of the respiratory tract as a whole or of any of its parts. [NIH] Restoration: Broad term applied to any inlay, crown, bridge or complete denture which restores or replaces loss of teeth or oral tissues. [NIH] Retina: The ten-layered nervous tissue membrane of the eye. It is continuous with the optic nerve and receives images of external objects and transmits visual impulses to the brain. Its outer surface is in contact with the choroid and the inner surface with the vitreous body. The outer-most layer is pigmented, whereas the inner nine layers are transparent. [NIH] Retinal: 1. Pertaining to the retina. 2. The aldehyde of retinol, derived by the oxidative enzymatic splitting of absorbed dietary carotene, and having vitamin A activity. In the retina, retinal combines with opsins to form visual pigments. One isomer, 11-cis retinal combines with opsin in the rods (scotopsin) to form rhodopsin, or visual purple. Another, all-trans retinal (trans-r.); visual yellow; xanthopsin) results from the bleaching of rhodopsin by light, in which the 11-cis form is converted to the all-trans form. Retinal also combines with opsins in the cones (photopsins) to form the three pigments responsible for colour vision. Called also retinal, and retinene1. [EU] Retinoblastoma: An eye cancer that most often occurs in children younger than 5 years. It occurs in hereditary and nonhereditary (sporadic) forms. [NIH] Retinol: Vitamin A. It is essential for proper vision and healthy skin and mucous membranes. Retinol is being studied for cancer prevention; it belongs to the family of drugs called retinoids. [NIH] Retrograde: 1. Moving backward or against the usual direction of flow. 2. Degenerating, deteriorating, or catabolic. [EU] Retrospective: Looking back at events that have already taken place. [NIH] Retroviral vector: RNA from a virus that is used to insert genetic material into cells. [NIH]
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Rhabdomyosarcoma: A malignant tumor of muscle tissue. [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] Rhodopsin: A photoreceptor protein found in retinal rods. It is a complex formed by the binding of retinal, the oxidized form of retinol, to the protein opsin and undergoes a series of complex reactions in response to visible light resulting in the transmission of nerve impulses to the brain. [NIH] Ribosome: A granule of protein and RNA, synthesized in the nucleolus and found in the cytoplasm of cells. Ribosomes are the main sites of protein synthesis. Messenger RNA attaches to them and there receives molecules of transfer RNA bearing amino acids. [NIH] Rigidity: Stiffness or inflexibility, chiefly that which is abnormal or morbid; rigor. [EU] Risk factor: A habit, trait, condition, or genetic alteration that increases a person's chance of developing a disease. [NIH] Rod: A reception for vision, located in the retina. [NIH] 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] Sarcomere: The repeating structural unit of a striated muscle fiber. [NIH] Satellite: Applied to a vein which closely accompanies an artery for some distance; in cytogenetics, a chromosomal agent separated by a secondary constriction from the main body of the chromosome. [NIH] Saturate: Means fatty acids without double bond. [NIH] Scans: Pictures of structures inside the body. Scans often used in diagnosing, staging, and monitoring disease include liver scans, bone scans, and computed tomography (CT) or computerized axial tomography (CAT) scans and magnetic resonance imaging (MRI) scans. In liver scanning and bone scanning, radioactive substances that are injected into the bloodstream collect in these organs. A scanner that detects the radiation is used to create pictures. In CT scanning, an x-ray machine linked to a computer is used to produce detailed pictures of organs inside the body. MRI scans use a large magnet connected to a computer to create pictures of areas inside the body. [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] Scleroproteins: Simple proteins characterized by their insolubility and fibrous structure.
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Within the body, they perform a supportive or protective function. [NIH] Sclerosis: A pathological process consisting of hardening or fibrosis of an anatomical structure, often a vessel or a nerve. [NIH] Scoliosis: A lateral curvature of the spine. [NIH] Screening: Checking for disease when there are no symptoms. [NIH] Scrotum: In males, the external sac that contains the testicles. [NIH] Secondary tumor: Cancer that has spread from the organ in which it first appeared to another organ. For example, breast cancer cells may spread (metastasize) to the lungs and cause the growth of a new tumor. When this happens, the disease is called metastatic breast cancer, and the tumor in the lungs is called a secondary tumor. Also called secondary cancer. [NIH] Secretion: 1. The process of elaborating a specific product as a result of the activity of a gland; this activity may range from separating a specific substance of the blood to the elaboration of a new chemical substance. 2. Any substance produced by secretion. [EU] Secretory: Secreting; relating to or influencing secretion or the secretions. [NIH] Secretory Vesicles: Vesicles derived from the golgi apparatus containing material to be released at the cell surface. [NIH] Sedimentation: The act of causing the deposit of sediment, especially by the use of a centrifugal machine. [EU] Segregation: The separation in meiotic cell division of homologous chromosome pairs and their contained allelomorphic gene pairs. [NIH] Selenium: An element with the atomic symbol Se, atomic number 34, and atomic weight 78.96. It is an essential micronutrient for mammals and other animals but is toxic in large amounts. Selenium protects intracellular structures against oxidative damage. It is an essential component of glutathione peroxidase. [NIH] Selenomethionine: Diagnostic aid in pancreas function determination. [NIH] Self Care: Performance of activities or tasks traditionally performed by professional health care providers. The concept includes care of oneself or one's family and friends. [NIH] Self-Help Groups: Organizations which provide an environment encouraging social interactions through group activities or individual relationships especially for the purpose of rehabilitating or supporting patients, individuals with common health problems, or the elderly. They include therapeutic social clubs. [NIH] Semen: The thick, yellowish-white, viscid fluid secretion of male reproductive organs discharged upon ejaculation. In addition to reproductive organ secretions, it contains spermatozoa and their nutrient plasma. [NIH] Senescence: The bodily and mental state associated with advancing age. [NIH] Senile: Relating or belonging to old age; characteristic of old age; resulting from infirmity of old age. [NIH] 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] Sensor: A device designed to respond to physical stimuli such as temperature, light, magnetism or movement and transmit resulting impulses for interpretation, recording, movement, or operating control. [NIH] Sepsis: The presence of bacteria in the bloodstream. [NIH]
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Sequence Analysis: A multistage process that includes the determination of a sequence (protein, carbohydrate, etc.), its fragmentation and analysis, and the interpretation of the resulting sequence information. [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] Sequencing: The determination of the order of nucleotides in a DNA or RNA chain. [NIH] Sequester: A portion of dead bone which has become detached from the healthy bone tissue, as occurs in necrosis. [NIH] Serine: A non-essential amino acid occurring in natural form as the L-isomer. It is synthesized from glycine or threonine. It is involved in the biosynthesis of purines, pyrimidines, and other amino acids. [NIH] Serotonin: A biochemical messenger and regulator, synthesized from the essential amino acid L-tryptophan. In humans it is found primarily in the central nervous system, gastrointestinal tract, and blood platelets. Serotonin mediates several important physiological functions including neurotransmission, gastrointestinal motility, hemostasis, and cardiovascular integrity. Multiple receptor families (receptors, serotonin) explain the broad physiological actions and distribution of this biochemical mediator. [NIH] Serous: Having to do with serum, the clear liquid part of blood. [NIH] Serum: The clear liquid part of the blood that remains after blood cells and clotting proteins have been removed. [NIH] Sex Characteristics: Those characteristics that distinguish one sex from the other. The primary sex characteristics are the ovaries and testes and their related hormones. Secondary sex characteristics are those which are masculine or feminine but not directly related to reproduction. [NIH] Shock: The general bodily disturbance following a severe injury; an emotional or moral upset occasioned by some disturbing or unexpected experience; disruption of the circulation, which can upset all body functions: sometimes referred to as circulatory shock. [NIH]
Side effect: A consequence other than the one(s) for which an agent or measure is used, as the adverse effects produced by a drug, especially on a tissue or organ system other than the one sought to be benefited by its administration. [EU] Signal Transduction: The intercellular or intracellular transfer of information (biological activation/inhibition) through a signal pathway. In each signal transduction system, an activation/inhibition signal from a biologically active molecule (hormone, neurotransmitter) is mediated via the coupling of a receptor/enzyme to a second messenger system or to an ion channel. Signal transduction plays an important role in activating cellular functions, cell differentiation, and cell proliferation. Examples of signal transduction systems are the GABA-postsynaptic receptor-calcium ion channel system, the receptor-mediated T-cell activation pathway, and the receptor-mediated activation of phospholipases. Those coupled to membrane depolarization or intracellular release of calcium include the receptormediated activation of cytotoxic functions in granulocytes and the synaptic potentiation of protein kinase activation. Some signal transduction pathways may be part of larger signal transduction pathways; for example, protein kinase activation is part of the platelet activation signal pathway. [NIH] 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
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cartilage. [NIH] Skull: The skeleton of the head including the bones of the face and the bones enclosing the brain. [NIH] Small intestine: The part of the digestive tract that is located between the stomach and the large intestine. [NIH] 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] Sodium Channels: Cell membrane glycoproteins selective for sodium ions. Fast sodium current is associated with the action potential in neural membranes. [NIH] Sodium Selenite: Selenious acid, disodium salt. It is used therapeutically to supply the trace element selenium. [NIH] Soft tissue: Refers to muscle, fat, fibrous tissue, blood vessels, or other supporting tissue of the body. [NIH] Solid tumor: Cancer of body tissues other than blood, bone marrow, or the lymphatic system. [NIH] 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] Somatic cells: All the body cells except the reproductive (germ) cells. [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] Spastic: 1. Of the nature of or characterized by spasms. 2. Hypertonic, so that the muscles are stiff and the movements awkward. 3. A person exhibiting spasticity, such as occurs in spastic paralysis or in cerebral palsy. [EU] Spasticity: A state of hypertonicity, or increase over the normal tone of a muscle, with heightened deep tendon reflexes. [EU]
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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] Specific immune cells: Immune cells such as T and B lymphocytes that respond to a single, specific antigen. [NIH] 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]
Spectrometer: An apparatus for determining spectra; measures quantities such as wavelengths and relative amplitudes of components. [NIH] Spectroscopic: The recognition of elements through their emission spectra. [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] Speech pathologist: A specialist who evaluates and treats people with communication and swallowing problems. Also called a speech therapist. [NIH] Sperm: The fecundating fluid of the male. [NIH] Spermatogenesis: Process of formation and development of spermatozoa, including spermatocytogenesis and spermiogenesis. [NIH] Spherocytes: Small, abnormal spherical red blood cells with more than the normal amount of hemoglobin. [NIH] Spherocytosis: A condition in which there are abnormally thick, almost spherical, red blood cells or spherocytes in the blood. [NIH] Sphincter: A ringlike band of muscle fibres that constricts a passage or closes a natural orifice; called also musculus sphincter. [EU] 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] Spinal Nerves: The 31 paired peripheral nerves formed by the union of the dorsal and ventral spinal roots from each spinal cord segment. The spinal nerve plexuses and the spinal roots are also included. [NIH]
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Spinous: Like a spine or thorn in shape; having spines. [NIH] Spirometry: Measurement of volume of air inhaled or exhaled by the lung. [NIH] Sporadic: Neither endemic nor epidemic; occurring occasionally in a random or isolated manner. [EU] Stabilization: The creation of a stable state. [EU] Stabilizer: A device for maintaining constant X-ray tube voltage or current. [NIH] Staging: Performing exams and tests to learn the extent of the cancer within the body, especially whether the disease has spread from the original site to other parts of the body. [NIH]
Statistically significant: Describes a mathematical measure of difference between groups. The difference is said to be statistically significant if it is greater than what might be expected to happen by chance alone. [NIH] 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] Stenosis: Narrowing or stricture of a duct or canal. [EU] Stent: A device placed in a body structure (such as a blood vessel or the gastrointestinal tract) to provide support and keep the structure open. [NIH] Sterile: Unable to produce children. [NIH] Sterility: 1. The inability to produce offspring, i.e., the inability to conceive (female s.) or to induce conception (male s.). 2. The state of being aseptic, or free from microorganisms. [EU] Steroid: A group name for lipids that contain a hydrogenated cyclopentanoperhydrophenanthrene ring system. Some of the substances included in this group are progesterone, adrenocortical hormones, the gonadal hormones, cardiac aglycones, bile acids, sterols (such as cholesterol), toad poisons, saponins, and some of the carcinogenic hydrocarbons. [EU] Stimulant: 1. Producing stimulation; especially producing stimulation by causing tension on muscle fibre through the nervous tissue. 2. An agent or remedy that produces stimulation. [EU]
Stimulus: That which can elicit or evoke action (response) in a muscle, nerve, gland or other excitable issue, or cause an augmenting action upon any function or metabolic process. [NIH] Stoma: A surgically created opening from an area inside the body to the outside. [NIH] Stomach: An organ of digestion situated in the left upper quadrant of the abdomen between the termination of the esophagus and the beginning of the duodenum. [NIH] Stool: The waste matter discharged in a bowel movement; feces. [NIH] Strand: DNA normally exists in the bacterial nucleus in a helix, in which two strands are coiled together. [NIH] Stress: Forcibly exerted influence; pressure. Any condition or situation that causes strain or tension. Stress may be either physical or psychologic, or both. [NIH]
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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] Subacute: Somewhat acute; between acute and chronic. [EU] Subclinical: Without clinical manifestations; said of the early stage(s) of an infection or other disease or abnormality before symptoms and signs become apparent or detectable by clinical examination or laboratory tests, or of a very mild form of an infection or other disease or abnormality. [EU] Subcutaneous: Beneath the skin. [NIH] Submaxillary: Four to six lymph glands, located between the lower jaw and the submandibular salivary gland. [NIH] Subspecies: A category intermediate in rank between species and variety, based on a smaller number of correlated characters than are used to differentiate species and generally conditioned by geographical and/or ecological occurrence. [NIH] Substrate: A substance upon which an enzyme acts. [EU] Substrate Specificity: A characteristic feature of enzyme activity in relation to the kind of substrate on which the enzyme or catalytic molecule reacts. [NIH] Sudden cardiac death: Cardiac arrest caused by an irregular heartbeat. [NIH] Sulfur: An element that is a member of the chalcogen family. It has an atomic symbol S, atomic number 16, and atomic weight 32.066. It is found in the amino acids cysteine and methionine. [NIH] 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] Suppressive: Tending to suppress : effecting suppression; specifically : serving to suppress activity, function, symptoms. [EU] 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] Symphysis: A secondary cartilaginous joint. [NIH] Symptomatic: Having to do with symptoms, which are signs of a condition or disease. [NIH] Synapse: The region where the processes of two neurons come into close contiguity, and the nervous impulse passes from one to the other; the fibers of the two are intermeshed, but, according to the general view, there is no direct contiguity. [NIH] 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
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meiosis). [EU] Synergistic: Acting together; enhancing the effect of another force or agent. [EU] Systemic: Affecting the entire body. [NIH] Systemic disease: Disease that affects the whole body. [NIH] Systemic lupus erythematosus: SLE. A chronic inflammatory connective tissue disease marked by skin rashes, joint pain and swelling, inflammation of the kidneys, inflammation of the fibrous tissue surrounding the heart (i.e., the pericardium), as well as other problems. Not all affected individuals display all of these problems. May be referred to as lupus. [NIH] Systolic: Indicating the maximum arterial pressure during contraction of the left ventricle of the heart. [EU] Tachycardia: Excessive rapidity in the action of the heart, usually with a heart rate above 100 beats per minute. [NIH] Telencephalon: Paired anteriolateral evaginations of the prosencephalon plus the lamina terminalis. The cerebral hemispheres are derived from it. Many authors consider cerebrum a synonymous term to telencephalon, though a minority include diencephalon as part of the cerebrum (Anthoney, 1994). [NIH] Telomere: A terminal section of a chromosome which has a specialized structure and which is involved in chromosomal replication and stability. Its length is believed to be a few hundred base pairs. [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] Terminator: A DNA sequence sited at the end of a transcriptional unit that signals the end of transcription. [NIH] Testicles: The two egg-shaped glands found inside the scrotum. They produce sperm and male hormones. Also called testes. [NIH] Testicular: Pertaining to a testis. [EU] Testis: Either of the paired male reproductive glands that produce the male germ cells and the male hormones. [NIH] Tetracycline: An antibiotic originally produced by Streptomyces viridifaciens, but used mostly in synthetic form. It is an inhibitor of aminoacyl-tRNA binding during protein synthesis. [NIH] Tetrodotoxin: Octahydro-12-(hydroxymethyl)-2-imino-5,9:7,10a-dimethano10aH(1,3)dioxocino(6,5-a)pyrimidine-4,7,10,11,12-pentol. An aminoperhydroquinazoline poison found mainly in the liver and ovaries of fishes in the order Tetradontiformes (pufferfish, globefish, toadfish), which are eaten. The toxin causes paresthesia and paralysis through interference with neuromuscular conduction. [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] Thalassemia: A group of hereditary hemolytic anemias in which there is decreased synthesis of one or more hemoglobin polypeptide chains. There are several genetic types with clinical pictures ranging from barely detectable hematologic abnormality to severe and
432 Muscular Dystrophy
fatal anemia. [NIH] Therapeutics: The branch of medicine which is concerned with the treatment of diseases, palliative or curative. [NIH] Thermal: Pertaining to or characterized by heat. [EU] Thigh: A leg; in anatomy, any elongated process or part of a structure more or less comparable to a leg. [NIH] Thoracic: Having to do with the chest. [NIH] Thorax: A part of the trunk between the neck and the abdomen; the chest. [NIH] Threonine: An essential amino acid occurring naturally in the L-form, which is the active form. It is found in eggs, milk, gelatin, and other proteins. [NIH] Threshold: For a specified sensory modality (e. g. light, sound, vibration), the lowest level (absolute threshold) or smallest difference (difference threshold, difference limen) or intensity of the stimulus discernible in prescribed conditions of stimulation. [NIH] Thrombin: An enzyme formed from prothrombin that converts fibrinogen to fibrin. (Dorland, 27th ed) EC 3.4.21.5. [NIH] 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] Thyroid: A gland located near the windpipe (trachea) that produces thyroid hormone, which helps regulate growth and metabolism. [NIH] Tic: An involuntary compulsive, repetitive, stereotyped movement, resembling a purposeful movement because it is coordinated and involves muscles in their normal synergistic relationships; tics usually involve the face and shoulders. [EU] Tidal Volume: The volume of air inspired or expired during each normal, quiet respiratory cycle. Common abbreviations are TV or V with subscript T. [NIH] Tin: A trace element that is required in bone formation. It has the atomic symbol Sn, atomic number 50, and atomic weight 118.71. [NIH] Tissue: A group or layer of cells that are alike in type and work together to perform a specific function. [NIH] Tissue Culture: Maintaining or growing of tissue, organ primordia, or the whole or part of an organ in vitro so as to preserve its architecture and/or function (Dorland, 28th ed). Tissue culture includes both organ culture and cell culture. [NIH] Tomography: Imaging methods that result in sharp images of objects located on a chosen plane and blurred images located above or below the plane. [NIH] Tone: 1. The normal degree of vigour and tension; in muscle, the resistance to passive elongation or stretch; tonus. 2. A particular quality of sound or of voice. 3. To make permanent, or to change, the colour of silver stain by chemical treatment, usually with a heavy metal. [EU] Tonic: 1. Producing and restoring the normal tone. 2. Characterized by continuous tension. 3. A term formerly used for a class of medicinal preparations believed to have the power of restoring normal tone to tissue. [EU] Tonicity: The normal state of muscular tension. [NIH] Tonus: A state of slight tension usually present in muscles even when they are not undergoing active contraction. [NIH]
Dictionary 433
Tooth Preparation: Procedures carried out with regard to the teeth or tooth structures preparatory to specified dental therapeutic and surgical measures. [NIH] Topical: On the surface of the body. [NIH] Torsion: A twisting or rotation of a bodily part or member on its axis. [NIH] Tourniquet: A device, band or elastic tube applied temporarily to press upon an artery to stop bleeding; a device to compress a blood vessel in order to stop bleeding. [NIH] Toxic: Having to do with poison or something harmful to the body. Toxic substances usually cause unwanted side effects. [NIH] Toxicity: The quality of being poisonous, especially the degree of virulence of a toxic microbe or of a poison. [EU] Toxicology: The science concerned with the detection, chemical composition, and pharmacologic action of toxic substances or poisons and the treatment and prevention of toxic manifestations. [NIH] Toxin: A poison; frequently used to refer specifically to a protein produced by some higher plants, certain animals, and pathogenic bacteria, which is highly toxic for other living organisms. Such substances are differentiated from the simple chemical poisons and the vegetable alkaloids by their high molecular weight and antigenicity. [EU] Toxoplasmosis: The acquired form of infection by Toxoplasma gondii in animals and man. [NIH]
Trace element: Substance or element essential to plant or animal life, but present in extremely small amounts. [NIH] Trachea: The cartilaginous and membranous tube descending from the larynx and branching into the right and left main bronchi. [NIH] Traction: The act of pulling. [NIH] Transaminases: A subclass of enzymes of the transferase class that catalyze the transfer of an amino group from a donor (generally an amino acid) to an acceptor (generally a 2-keto acid). Most of these enzymes are pyridoxyl phosphate proteins. (Dorland, 28th ed) EC 2.6.1. [NIH]
Transcription Factors: Endogenous substances, usually proteins, which are effective in the initiation, stimulation, or termination of the genetic transcription process. [NIH] Transduction: The transfer of genes from one cell to another by means of a viral (in the case of bacteria, a bacteriophage) vector or a vector which is similar to a virus particle (pseudovirion). [NIH] Transfection: The uptake of naked or purified DNA into cells, usually eukaryotic. It is analogous to bacterial transformation. [NIH] Transferases: Transferases are enzymes transferring a group, for example, the methyl group or a glycosyl group, from one compound (generally regarded as donor) to another compound (generally regarded as acceptor). The classification is based on the scheme "donor:acceptor group transferase". (Enzyme Nomenclature, 1992) EC 2. [NIH] Transforming Growth Factor beta: A factor synthesized in a wide variety of tissues. It acts synergistically with TGF-alpha in inducing phenotypic transformation and can also act as a negative autocrine growth factor. TGF-beta has a potential role in embryonal development, cellular differentiation, hormone secretion, and immune function. TGF-beta is found mostly as homodimer forms of separate gene products TGF-beta1, TGF-beta2 or TGF-beta3. Heterodimers composed of TGF-beta1 and 2 (TGF-beta1.2) or of TGF-beta2 and 3 (TGFbeta2.3) have been isolated. The TGF-beta proteins are synthesized as precursor proteins. [NIH]
434 Muscular Dystrophy
Transgenes: Genes that are introduced into an organism using gene transfer techniques. [NIH]
Translation: The process whereby the genetic information present in the linear sequence of ribonucleotides in mRNA is converted into a corresponding sequence of amino acids in a protein. It occurs on the ribosome and is unidirectional. [NIH] Translational: The cleavage of signal sequence that directs the passage of the protein through a cell or organelle membrane. [NIH] Translocation: The movement of material in solution inside the body of the plant. [NIH] 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] Trinucleotide Repeats: Microsatellite repeats consisting of three nucleotides dispersed in the euchromatic arms of chromosomes. [NIH] Trophic: Of or pertaining to nutrition. [EU] Trophoblast: The outer layer of cells of the blastocyst which works its way into the endometrium during ovum implantation and grows rapidly, later combining with mesoderm. [NIH] Tropomyosin: A protein found in the thin filaments of muscle fibers. It inhibits contraction of the muscle unless its position is modified by troponin. [NIH] Troponin: One of the minor protein components of skeletal muscle. Its function is to serve as the calcium-binding component in the troponin-tropomyosin B-actin-myosin complex by conferring calcium sensitivity to the cross-linked actin and myosin filaments. [NIH] Tryptophan: An essential amino acid that is necessary for normal growth in infants and for nitrogen balance in adults. It is a precursor serotonin and niacin. [NIH] Tubulin: A microtubule subunit protein found in large quantities in mammalian brain. It has also been isolated from sperm flagella, cilia, and other sources. Structurally, the protein is a dimer with a molecular weight of approximately 120,000 and a sedimentation coefficient of 5.8S. It binds to colchicine, vincristine, and vinblastine. [NIH] Tumor Necrosis Factor: Serum glycoprotein produced by activated macrophages and other mammalian mononuclear leukocytes which has necrotizing activity against tumor cell lines and increases ability to reject tumor transplants. It mimics the action of endotoxin but differs from it. It has a molecular weight of less than 70,000 kDa. [NIH] Tyrosine: A non-essential amino acid. In animals it is synthesized from phenylalanine. It is also the precursor of epinephrine, thyroid hormones, and melanin. [NIH] Ubiquitin: A highly conserved 76 amino acid-protein found in all eukaryotic cells. [NIH] Umbilical Arteries: Either of a pair of arteries originating from the internal iliac artery and passing through the umbilical cord to carry blood from the fetus to the placenta. [NIH] Umbilical Cord: The flexible structure, giving passage to the umbilical arteries and vein, which connects the embryo or fetus to the placenta. [NIH] Umbilical cord blood: Blood from the placenta (afterbirth) that contains high concentrations of stem cells needed to produce new blood cells. [NIH] Unconscious: Experience which was once conscious, but was subsequently rejected, as the
Dictionary 435
"personal unconscious". [NIH] Urea: A compound (CO(NH2)2), formed in the liver from ammonia produced by the deamination of amino acids. It is the principal end product of protein catabolism and constitutes about one half of the total urinary solids. [NIH] Ureters: Tubes that carry urine from the kidneys to the bladder. [NIH] Urethra: The tube through which urine leaves the body. It empties urine from the bladder. [NIH]
Uric: A kidney stone that may result from a diet high in animal protein. When the body breaks down this protein, uric acid levels rise and can form stones. [NIH] Urinary: Having to do with urine or the organs of the body that produce and get rid of urine. [NIH] Urinary tract: The organs of the body that produce and discharge urine. These include the kidneys, ureters, bladder, and urethra. [NIH] Urine: Fluid containing water and waste products. Urine is made by the kidneys, stored in the bladder, and leaves the body through the urethra. [NIH] Uterus: The small, hollow, pear-shaped organ in a woman's pelvis. This is the organ in which a fetus develops. Also called the womb. [NIH] Vaccine: A substance or group of substances meant to cause the immune system to respond to a tumor or to microorganisms, such as bacteria or viruses. [NIH] Vacuole: A fluid-filled cavity within the cytoplasm of a cell. [NIH] Vagina: The muscular canal extending from the uterus to the exterior of the body. Also called the birth canal. [NIH] 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]
Vascular: Pertaining to blood vessels or indicative of a copious blood supply. [EU] Vascular Resistance: An expression of the resistance offered by the systemic arterioles, and to a lesser extent by the capillaries, to the flow of blood. [NIH] Vasoconstriction: Narrowing of the blood vessels without anatomic change, for which constriction, pathologic is used. [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] Venom: That produced by the poison glands of the mouth and injected by the fangs of poisonous snakes. [NIH] Venous: Of or pertaining to the veins. [EU] Venous blood: Blood that has given up its oxygen to the tissues and carries carbon dioxide back for gas exchange. [NIH] Ventilation: 1. In respiratory physiology, the process of exchange of air between the lungs and the ambient air. Pulmonary ventilation (usually measured in litres per minute) refers to the total exchange, whereas alveolar ventilation refers to the effective ventilation of the alveoli, in which gas exchange with the blood takes place. 2. In psychiatry, verbalization of one's emotional problems. [EU]
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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 body through the aorta. [NIH] Ventricular: Pertaining to a ventricle. [EU] Ventricular Dysfunction: A condition in which the ventricles of the heart exhibit a decreased functionality. [NIH] Ventricular fibrillation: Rapid, irregular quivering of the heart's ventricles, with no effective heartbeat. [NIH] Ventricular Function: The hemodynamic and electrophysiological action of the ventricles. [NIH]
Venules: The minute vessels that collect blood from the capillary plexuses and join together to form veins. [NIH] Vertebrae: A bony unit of the segmented spinal column. [NIH] Vertebral: Of or pertaining to a vertebra. [EU] Vesicular: 1. Composed of or relating to small, saclike bodies. 2. Pertaining to or made up of vesicles on the skin. [EU] Veterinary Medicine: The medical science concerned with the prevention, diagnosis, and treatment of diseases in animals. [NIH] Villus: Cell found in the lining of the small intestine. [NIH] Vimentin: An intermediate filament protein found in most differentiating cells, in cells grown in tissue culture, and in certain fully differentiated cells. Its insolubility suggests that it serves a structural function in the cytoplasm. MW 52,000. [NIH] Vinblastine: An anticancer drug that belongs to the family of plant drugs called vinca alkaloids. It is a mitotic inhibitor. [NIH] Vincristine: An anticancer drug that belongs to the family of plant drugs called vinca alkaloids. [NIH] Vinculin: A cytoskeletal protein associated with cell-cell and cell-matrix interactions. The amino acid sequence of human vinculin has been determined. The protein consists of 1066 amino acid residues and its gene has been assigned to chromosome 10. [NIH] Viral: Pertaining to, caused by, or of the nature of virus. [EU] Viral vector: A type of virus used in cancer therapy. The virus is changed in the laboratory and cannot cause disease. Viral vectors produce tumor antigens (proteins found on a tumor cell) and can stimulate an antitumor immune response in the body. Viral vectors may also be used to carry genes that can change cancer cells back to normal cells. [NIH] Virion: The infective system of a virus, composed of the viral genome, a protein core, and a protein coat called a capsid, which may be naked or enclosed in a lipoprotein envelope called the peplos. [NIH] Virulence: The degree of pathogenicity within a group or species of microorganisms or viruses as indicated by case fatality rates and/or the ability of the organism to invade the tissues of the host. [NIH] Virus: Submicroscopic organism that causes infectious disease. In cancer therapy, some viruses may be made into vaccines that help the body build an immune response to, and
Dictionary 437
kill, tumor cells. [NIH] Visceral: , from viscus a viscus) pertaining to a viscus. [EU] Visceral Afferents: The sensory fibers innervating the viscera. [NIH] Vital Capacity: The volume of air that is exhaled by a maximal expiration following a maximal inspiration. [NIH] Vitreous: Glasslike or hyaline; often used alone to designate the vitreous body of the eye (corpus vitreum). [EU] Vitreous Body: The transparent, semigelatinous substance that fills the cavity behind the crystalline lens of the eye and in front of the retina. It is contained in a thin hyoid membrane and forms about four fifths of the optic globe. [NIH] Vitro: Descriptive of an event or enzyme reaction under experimental investigation occurring outside a living organism. Parts of an organism or microorganism are used together with artificial substrates and/or conditions. [NIH] Vivo: Outside of or removed from the body of a living organism. [NIH] Voltage-gated: It is opened by the altered charge distribution across the cell membrane. [NIH]
Weight Gain: Increase in body weight over existing weight. [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] Womb: A hollow, thick-walled, muscular organ in which the impregnated ovum is developed into a child. [NIH] Wound Healing: Restoration of integrity to traumatized tissue. [NIH] Xenobiotics: Chemical substances that are foreign to the biological system. They include naturally occurring compounds, drugs, environmental agents, carcinogens, insecticides, etc. [NIH]
Xenograft: The cells of one species transplanted to another species. [NIH] X-ray: High-energy radiation used in low doses to diagnose diseases and in high doses to treat cancer. [NIH] X-ray therapy: The use of high-energy radiation from x-rays to kill cancer cells and shrink tumors. Radiation may come from a machine outside the body (external-beam radiation therapy) or from materials called radioisotopes. Radioisotopes produce radiation and can be placed in or near the tumor or in the area near cancer cells. This type of radiation treatment is called internal radiation therapy, implant radiation, interstitial radiation, or brachytherapy. Systemic radiation therapy uses a radioactive substance, such as a radiolabeled monoclonal antibody, that circulates throughout the body. X-ray therapy is also called radiation therapy, radiotherapy, and irradiation. [NIH] Yeasts: A general term for single-celled rounded fungi that reproduce by budding. Brewers' and bakers' yeasts are Saccharomyces cerevisiae; therapeutic dried yeast is dried yeast. [NIH]
438 Muscular Dystrophy
Zebrafish: A species of North American fishes of the family Cyprinidae. They are used in embryological studies and to study the effects of certain chemicals on development. [NIH] Zygote: The fertilized ovum. [NIH] Zymogen: Inactive form of an enzyme which can then be converted to the active form, usually by excision of a polypeptide, e. g. trypsinogen is the zymogen of trypsin. [NIH]
439
INDEX A Abdominal, 219, 359, 379, 394, 397, 400, 412, 414 Aberrant, 11, 24, 49, 103, 113, 149, 231, 359 Ablate, 28, 359 Acantholysis, 359, 413 Acceptor, 359, 400, 412, 433 Acetylcholine, 38, 41, 88, 89, 264, 359, 361, 373, 408, 409 Acetylcholinesterase, 89, 359 Acetylglucosamine, 234, 359, 390 Acidity, 359, 415 Actin, 15, 18, 25, 38, 62, 97, 98, 103, 217, 234, 257, 280, 359, 404, 406, 407, 434 Actinin, 7, 99, 149, 359, 381 Action Potentials, 95, 289, 359 Activities of Daily Living, 22, 211, 301, 359 Actomyosin, 103, 254, 359 Acuity, 256, 359 Acyl, 359, 403 Adaptability, 359, 371 Adaptation, 74, 359, 416 Adenosine, 360, 415 Adenovirus, 8, 34, 50, 59, 360 Adipose Tissue, 5, 33, 206, 264, 296, 360 Adjunctive Therapy, 360, 407 Adjustment, 225, 258, 359, 360 Adolescence, 279, 294, 337, 345, 360 Adrenergic, 360, 361, 383 Adverse Effect, 270, 360, 426 Aerobic, 360, 405 Aetiology, 174, 360 Afferent, 360, 385 Affinity, 36, 57, 60, 75, 90, 283, 360, 364, 401, 427 Affinity Chromatography, 57, 360 Age Groups, 36, 360 Aged, 80 and Over, 360 Ageing, 49, 360 Agonist, 360, 361 Agrin, 38, 76, 89, 361 Air Sacs, 361 Airway, 103, 115, 185, 202, 361 Airway Resistance, 103, 361 Albuterol, 208, 268, 269, 270, 361 Algorithms, 361, 367 Alkaline, 42, 361, 362, 369, 415 Alkaline Phosphatase, 42, 361
Alkaloid, 361, 365, 374 Alleles, 58, 72, 84, 278, 361, 392, 400 Allogeneic, 296, 361 Alpha-helix, 361, 398 Alternative medicine, 316, 361 Alternative Splicing, 72, 90, 361, 419 Alveoli, 40, 361, 435 Ameliorating, 163, 361 Amine, 361, 392 Amino Acid Sequence, 27, 29, 34, 282, 285, 362, 363, 384, 388, 436 Amino Acid Substitution, 27, 362 Ammonia, 361, 362, 389, 435 Amplification, 66, 362 Amygdala, 362, 366, 431 Amyotrophy, 289, 362 Anabolic, 103, 362, 412 Anaesthesia, 114, 116, 124, 166, 173, 174, 219, 221, 226, 230, 236, 253, 257, 362, 395 Anal, 362, 386, 400 Analogous, 10, 27, 71, 362, 393, 433 Anaphylatoxins, 362, 375 Anatomical, 47, 145, 362, 365, 373, 376, 382, 395, 404, 425 Androgenic, 362, 412 Anemia, 19, 100, 163, 362, 393, 402, 432 Anesthesia, 29, 215, 361, 362, 378, 408 Anesthetics, 173, 362, 383 Angiogenesis, 53, 363 Ankle, 178, 231, 363 Ankyrin Repeat, 137, 363 Annealing, 51, 363, 417 Anomalies, 78, 363 Anterior Cerebral Artery, 363, 372 Antibacterial, 363, 428 Antibiotic, 29, 270, 363, 414, 428, 431 Anticoagulant, 363, 419 Antigen, 8, 285, 360, 363, 364, 375, 393, 395, 396, 403, 404, 428 Antigen-Antibody Complex, 363, 375 Anti-infective, 363, 393, 398 Anti-inflammatory, 363, 377, 389, 413, 418 Antioxidant, 363, 412 Antiserum, 285, 364 Antiviral, 364, 396, 414 Anus, 362, 364, 365, 368, 374 Anxiety, 364, 410 Aorta, 364, 394, 418, 436
440 Muscular Dystrophy
Apamin, 17, 95, 279, 364 Apoptosis, 14, 31, 40, 77, 80, 126, 221, 228, 364, 370 Applicability, 102, 364 Aptitude, 364, 420 Aqueous, 364, 366, 378, 382, 393, 399 Arginine, 20, 362, 364, 409 Arterial, 34, 364, 372, 394, 420, 431 Arteries, 364, 367, 368, 377, 394, 404, 434 Arterioles, 364, 368, 435 Artery, 8, 363, 364, 377, 385, 421, 424, 433 Articular, 364, 411 Ascending Colon, 197, 364 Aseptic, 364, 411, 429 Assay, 47, 51, 104, 105, 112, 264, 291, 364 Astrocytes, 11, 169, 206, 364, 392, 404 Asymptomatic, 117, 166, 364 Ataxia, 19, 118, 269, 344, 364, 431 Atracurium, 174, 365 Atresia, 86, 365 Atrial, 128, 365 Atrial Fibrillation, 128, 365 Atrioventricular, 80, 124, 168, 365 Atrium, 365, 436 Atrophy, 70, 93, 151, 236, 250, 279, 281, 359, 365, 400, 408, 417, 418 Atropine, 293, 365, 366 Atypical, 164, 266, 365 Autoantibodies, 16, 365 Autoantigens, 365 Autoimmune disease, 21, 86, 365, 406 Autologous, 296, 365 Autonomic, 55, 125, 170, 198, 293, 294, 359, 365, 366, 414, 427, 430 Autonomic Nervous System, 293, 294, 365, 366, 414, 427, 430 Autoradiography, 41, 365 Avian, 37, 248, 256, 365 Axillary, 173, 365 Axonal, 58, 95, 365 Axons, 52, 366, 411 B Bacteria, 359, 363, 366, 367, 372, 382, 385, 391, 401, 404, 416, 425, 428, 433, 435 Bacterial Infections, 86, 366, 372 Bacterial Physiology, 360, 366 Bacteriophage, 366, 433 Bacterium, 86, 366, 391, 411, 422 Band 3 Protein, 363, 366 Baroreflex, 293, 366 Basal Ganglia, 365, 366, 368, 406 Basal Ganglia Diseases, 365, 366, 406
Base, 19, 205, 366, 379, 387, 388, 398, 414, 415, 416, 431 Base Sequence, 366, 387, 388 Basement Membrane, 16, 32, 52, 57, 85, 366, 384, 399 Belladonna, 365, 366 Benign, 35, 282, 288, 366, 390, 421 Bifida, 367 Bilateral, 367, 413 Bile, 367, 387, 393, 400, 429 Binding Sites, 48, 90, 367 Bioengineering, 13, 97, 322, 367 Biogenesis, 91, 367 Biological response modifier, 367, 396 Biological therapy, 367, 390 Bioluminescence, 194, 367 Biopsy, 21, 35, 42, 43, 54, 153, 170, 171, 243, 269, 271, 283, 306, 356, 357, 367, 414 Biopsy specimen, 54, 367 Biotechnology, 53, 106, 109, 304, 316, 323, 367 Bladder, 121, 347, 367, 387, 406, 408, 419, 435 Blastocyst, 367, 375, 412, 416, 434 Blepharoptosis, 132, 229, 367 Blister, 367, 413 Blood Coagulation, 367, 369, 386, 432 Blood pressure, 366, 367, 370, 394, 405, 414, 427 Blood-Brain Barrier, 11, 368 Blot, 278, 368 Body Composition, 47, 147, 215, 368 Body Fluids, 368, 380, 410, 427 Bone Density, 133, 368 Bone Marrow, 44, 53, 78, 107, 183, 194, 296, 368, 388, 401, 427, 429 Bone Marrow Transplantation, 78, 107, 183, 296, 368 Bone scan, 368, 424 Bowel, 347, 362, 368, 379, 395, 397, 408, 429 Bowel Movement, 368, 379, 429 Brachial, 368, 393 Brachytherapy, 368, 397, 398, 421, 437 Bradykinin, 368, 409 Brain Diseases, 368, 413, 421 Brain Stem, 368, 372, 421 Branch, 6, 70, 119, 176, 249, 304, 353, 368, 378, 381, 401, 413, 428, 432 Breakdown, 205, 296, 368, 379, 387, 411 Breeding, 72, 369 Bronchial, 369, 392
Index 441
Bronchioles, 361, 369, 420 Bronchopulmonary, 47, 369 Bronchopulmonary Dysplasia, 47, 369 Buffers, 366, 369, 428 Bulbar, 369, 421 C Cachexia, 15, 73, 369 Calcium-Binding Proteins, 247, 369 Calculi, 369, 390 Callus, 369, 382 Calmodulin, 85, 369 Calpain, 20, 49, 54, 124, 156, 174, 192, 198, 215, 223, 225, 369 Camping, 304, 369 Capital Financing, 369, 418 Capsid, 369, 436 Carbohydrate, 52, 139, 369, 377, 390, 417, 426 Carbon Dioxide, 370, 378, 386, 387, 416, 423, 435 Carcinogenic, 370, 396, 410, 419, 429 Carcinogens, 370, 410, 437 Carcinoma, 35, 94, 370 Cardiac arrest, 124, 166, 179, 370, 430 Cardiac Output, 366, 370 Cardiovascular, 34, 63, 92, 119, 125, 176, 195, 230, 233, 248, 365, 370, 426, 427 Cardiovascular disease, 63, 92, 230, 233, 370 Carnitine, 202, 246, 251, 370 Carotene, 370, 423 Case report, 120, 124, 136, 143, 144, 145, 151, 155, 170, 240, 370, 374 Case series, 370, 374 Caspase, 14, 126, 370 Catabolism, 87, 370 Cataract, 163, 187, 370 Catheter, 370, 397 Catheterization, 370, 397 Caudal, 371, 394, 417 Causal, 130, 371, 391 Caveolae, 13, 54, 126, 171, 172, 371 Caveolins, 14, 371 Cell Adhesion, 18, 34, 55, 63, 95, 371, 396 Cell Adhesion Molecules, 34, 95, 371 Cell Communication, 95, 371 Cell Death, 12, 14, 31, 154, 364, 371 Cell Differentiation, 6, 62, 69, 80, 100, 371, 426 Cell Division, 24, 366, 371, 378, 390, 397, 403, 405, 416, 419, 425 Cell Fusion, 27, 73, 371
Cell membrane, 12, 59, 289, 312, 371, 379, 384, 403, 415, 418, 427, 437 Cell Membrane Structures, 371 Cell motility, 76, 371, 392 Cell Polarity, 63, 107, 371 Cell proliferation, 371, 426 Cell Respiration, 371, 405, 423 Cell Survival, 14, 371, 390, 391 Cell Transplantation, 61, 254, 256, 372 Cerebellar, 92, 131, 186, 187, 231, 365, 372, 422 Cerebellum, 368, 372, 422 Cerebral Cortex, 156, 365, 368, 372, 386 Cerebral Infarction, 171, 372 Cerebral Palsy, 81, 305, 338, 339, 372, 427 Cerebrovascular, 12, 366, 370, 372, 431 Cerebrum, 372, 431 Cervical, 35, 185, 372 Cervix, 372, 386 Chaperonins, 372, 405 Character, 372, 378 Chemokines, 34, 95, 372 Chemotactic Factors, 372, 375 Chemotherapy, 289, 372 Chest wall, 219, 372 Chiasma, 372, 377 Chimeric Proteins, 89, 373 Chin, 157, 373, 403 Cholesterol, 265, 367, 371, 373, 377, 400, 403, 429 Choline, 172, 359, 373 Chondrocytes, 373, 386 Choroid, 373, 423 Chromatin, 33, 38, 40, 65, 80, 105, 108, 145, 364, 373, 383 Chromosomal, 7, 11, 16, 26, 105, 243, 362, 373, 416, 424, 431 Chromosome Fragility, 105, 373 Chronic, 37, 82, 97, 369, 373, 380, 382, 395, 399, 413, 417, 430, 431 Chronic Disease, 97, 369, 373 Chronic renal, 373, 417 Cirrhosis, 94, 373, 391 CIS, 30, 373, 423 Clamp, 48, 95, 373 Clear cell carcinoma, 373, 379 Cleft Palate, 48, 373 Clinical Medicine, 6, 248, 373, 418 Clinical study, 35, 373, 376 Clinical trial, 4, 30, 46, 62, 82, 129, 208, 254, 267, 272, 323, 374, 380, 420, 422 Clone, 17, 25, 26, 28, 40, 64, 65, 278, 374
442 Muscular Dystrophy
Cloning, 7, 16, 26, 31, 60, 64, 68, 75, 85, 86, 184, 367, 374, 396, 400 Cod Liver Oil, 374, 382 Codon, 52, 104, 146, 199, 374, 388 Coenzyme, 62, 247, 261, 262, 268, 374 Cofactor, 374, 420, 432 Cognition, 104, 374, 399 Colchicine, 374, 434 Colitis, 374, 395 Collagen, 16, 86, 109, 129, 143, 237, 276, 283, 362, 366, 374, 384, 386, 388, 416, 419 Collapse, 368, 374 Colloidal, 374, 381, 414 Colon, 19, 51, 364, 374, 395, 399 Combinatorial, 70, 72, 374 Complement, 26, 39, 91, 100, 362, 374, 375, 388, 396 Complementary and alternative medicine, 253, 262, 375 Complementary medicine, 253, 375 Complementation, 8, 48, 375 Compulsions, 375, 410 Computational Biology, 19, 323, 375 Computed tomography, 230, 368, 375, 424 Computerized tomography, 375 Concentric, 375, 409 Conception, 375, 385, 429 Concomitant, 13, 22, 247, 255, 376 Conduction, 80, 110, 115, 168, 171, 182, 279, 293, 334, 376, 431 Cone, 376, 415 Congenita, 306, 376 Congestive heart failure, 94, 376 Conjugated, 376, 378, 407, 410 Connective Tissue, 75, 284, 368, 374, 376, 386, 387, 388, 401, 404, 420, 424, 431 Connective Tissue Cells, 376 Consciousness, 376, 379, 380, 420, 421 Constitutional, 376, 407 Constriction, 376, 398, 424, 435 Constriction, Pathologic, 376, 435 Contamination, 8, 376 Continuum, 15, 376 Contractility, 22, 50, 103, 290, 376 Contracture, 112, 122, 306, 376 Contraindications, ii, 376 Controlled clinical trial, 62, 82, 376 Convulsions, 364, 376 Coordination, 341, 372, 376, 406 Cornea, 376 Corneal Diseases, 249, 376 Corneum, 376, 383, 394
Coronary, 370, 376, 377, 404 Coronary heart disease, 370, 377 Coronary Thrombosis, 377, 404 Corpuscle, 377, 384 Cortex, 247, 377, 418, 422 Cortical, 25, 57, 63, 103, 115, 186, 247, 377, 431 Corticosteroid, 377, 418 Cortisone, 377, 418 Cranial, 372, 377, 385, 390, 397, 411, 414, 421 Creatine, 62, 71, 76, 194, 198, 249, 251, 253, 258, 267, 269, 277, 282, 287, 288, 334, 357, 377 Creatine Kinase, 71, 76, 194, 198, 253, 277, 282, 334, 377 Creatinine, 42, 270, 357, 377 Crossing-over, 238, 377, 422 Crystallization, 24, 377 Cues, 95, 377 Cultured cells, 13, 75, 280, 377 Curare, 257, 377, 406 Curative, 46, 378, 409, 432 Cutaneous, 16, 85, 378, 401, 413 Cyclic, 87, 369, 371, 378, 390, 409 Cytochrome, 14, 378, 412 Cytogenetics, 378, 424 Cytokine, 34, 378 Cytokinesis, 24, 63, 378 Cytoplasm, 20, 23, 66, 67, 74, 90, 364, 371, 378, 383, 390, 396, 407, 409, 424, 435, 436 Cytotoxic, 21, 73, 102, 108, 378, 422, 426 Cytotoxicity, 29, 31, 378 D Data Collection, 82, 97, 378 De novo, 85, 116, 133, 146, 164, 167, 214, 378 Deamination, 378, 435 Decarboxylation, 378, 392 Decidua, 378, 416 Defense Mechanisms, 378, 396 Degenerative, 7, 33, 57, 65, 76, 87, 96, 289, 296, 334, 378, 411 Dehydroepiandrosterone, 289, 378 Dementia, 77, 379 Denaturation, 100, 379, 417 Dendrites, 379, 409 Density, 41, 42, 81, 103, 105, 106, 122, 368, 379, 400, 410, 427 Depolarization, 379, 426 Deprivation, 108, 225, 255, 379 DES, 247, 362, 379
Index 443
Desmin, 18, 82, 136, 379, 396 Desmosomes, 379, 391 Developmental Biology, 52, 379 Diabetes Mellitus, 379, 391, 418 Diagnostic procedure, 275, 316, 379 Diaphragm, 22, 30, 82, 135, 379 Diastole, 379 Diastolic, 117, 243, 379, 394 Digestion, 171, 367, 368, 379, 397, 400, 429 Digestive system, 273, 379, 387 Dilatation, 379, 418 Dilated cardiomyopathy, 9, 31, 32, 136, 137, 182, 200, 379 Diploid, 93, 375, 379, 416 Direct, iii, 5, 25, 40, 59, 66, 69, 70, 87, 91, 97, 104, 134, 136, 371, 373, 380, 401, 422, 430 Discrete, 24, 380, 419 Disease Progression, 50, 54, 267, 269, 280, 282, 340, 342, 344, 380 Dislocation, 165, 380 Dissection, 13, 47, 380 Dissociation, 6, 137, 360, 380 Distal, 17, 48, 64, 115, 137, 160, 167, 182, 289, 291, 336, 365, 380, 414, 420 Dominance, 90, 380, 383 Dorsal, 380, 417, 428 Double-blind, 62, 110, 267, 380 Drive, ii, vi, 5, 19, 245, 380 Drug Resistance, 18, 380 Drug Tolerance, 380 Duct, 370, 380, 412, 424, 429 Dwarfism, 246, 334, 380 Dysphagia, 163, 179, 228, 261, 380 Dysplasia, 186, 380 Dystonia, 10, 381 E Ectopic, 11, 381 Effector, 107, 359, 374, 381 Efferent, 381, 385, 406 Efficacy, 5, 12, 66, 82, 256, 267, 268, 289, 381 Elastic, 189, 381, 427, 433 Elastin, 374, 381, 384 Elective, 223, 381 Electrocardiogram, 113, 381 Electrocardiography, 219, 381 Electroencephalography, 88, 381, 402 Electrolyte, 377, 381, 410, 418, 427 Electron microscope, 41, 381 Electrophoresis, 105, 134, 140, 147, 214, 278, 285, 381
Electrophysiological, 55, 381, 436 Electroretinography, 139, 381 Elementary Particles, 381, 402, 409, 420 Embryo, 24, 37, 53, 75, 367, 371, 382, 385, 395, 404, 412, 434 Embryogenesis, 51, 382 Embryology, 382, 409 Emulsion, 250, 365, 382, 386 Enamel, 382, 398 Encephalocele, 382, 408 Endemic, 382, 402, 429 Endocytosis, 371, 382 Endogenous, 20, 50, 51, 139, 365, 369, 382, 419, 433 Endometrium, 378, 382, 434 Endothelial cell, 34, 368, 382, 386, 392, 432 Endothelium, 382, 409 Endothelium-derived, 382, 409 Endotoxin, 382, 434 End-stage renal, 373, 382, 417 Enhancer, 71, 204, 297, 382 Enterocytes, 94, 382 Enterovirus, 92, 383 Environmental Exposure, 47, 383, 410 Environmental Health, 322, 324, 383 Enzymatic, 19, 74, 362, 369, 370, 375, 383, 386, 392, 417, 423 Eosinophilic, 119, 383 Eosinophils, 73, 383, 390, 399 Epidemic, 383, 429 Epidermal, 16, 55, 86, 286, 295, 383, 398 Epidermal Growth Factor, 286, 295, 383 Epidermis, 16, 55, 85, 359, 367, 376, 383, 393, 394, 398, 413, 418, 421 Epidermolysis Bullosa, 52, 85, 133, 136, 150, 153, 166, 184, 199, 383 Epidermolysis Bullosa Simplex, 133, 136, 150, 166, 383 Epinephrine, 360, 383, 409, 434 Epistasis, 25, 383 Epithelial, 52, 55, 101, 378, 383, 390, 392, 399, 413 Epithelial Cells, 383, 392, 399 Epithelium, 366, 379, 382, 383 Epitope, 177, 384 Erythrocyte Membrane, 257, 366, 384, 428 Erythrocytes, 249, 254, 259, 362, 368, 369, 384, 391, 422 Esophageal, 147, 239, 384 Esophagus, 179, 365, 379, 384, 387, 415, 429 Eukaryotic Cells, 63, 384, 395, 411, 434
444 Muscular Dystrophy
Excitation, 36, 85, 95, 384, 409 Excitotoxicity, 77, 384 Exhaustion, 384, 402 Exocytosis, 40, 384 Exogenous, 382, 384, 388, 419 Exon, 16, 51, 74, 110, 130, 136, 141, 188, 199, 230, 283, 297, 361, 384 Expiration, 384, 423, 437 External-beam radiation, 384, 398, 421, 437 Extracellular Matrix Proteins, 11, 384, 391 Extracellular Space, 384 Extravasation, 34, 384 Extremity, 205, 384, 413 Eye Infections, 360, 385 Eye Movements, 221, 385, 421 F Facial, 4, 68, 75, 114, 150, 221, 291, 385, 427 Facial Expression, 385 Facial Nerve, 114, 385 Failure to Thrive, 345, 385 Family Planning, 323, 385 Fasciculation, 385, 408 Fat, 53, 360, 368, 370, 377, 385, 400, 406, 418, 424, 427 Fatigue, 385, 391 Fatty acids, 385, 424 Femoral, 46, 385 Femoral Artery, 46, 385 Femur, 385 Ferritin, 94, 385 Fetal Alcohol Syndrome, 300, 385 Fetal Development, 294, 385, 408 Fetus, 385, 416, 418, 434, 435 Fibrillation, 385 Fibrin, 98, 367, 385, 386, 432 Fibrinogen, 385, 432 Fibrinolysis, 129, 386 Fibroblast Growth Factor, 73, 118, 119, 285, 286, 294, 295, 386 Fibroblasts, 126, 139, 172, 295, 376, 386 Fibronectins, 384, 386 Fibrosis, 8, 81, 83, 94, 96, 305, 376, 386, 425 Fine-needle aspiration, 386, 408 Fissure, 373, 386 Fixation, 207, 221, 222, 226, 386 Flaccid, 211, 386 Flexion, 189, 386 Fluorescence, 44, 55, 80, 99, 165, 278, 386 Flutter, 128, 386 Fold, 72, 94, 286, 294, 363, 386 Forearm, 272, 368, 386
Founder Effect, 207, 386 Fovea, 386, 387 Frameshift, 52, 104, 154, 387 Frameshift Mutation, 52, 104, 387 Free Radicals, 77, 363, 380, 387 Friction, 361, 387 Frontal Lobe, 363, 372, 387 Fructose, 26, 387 Fundus, 386, 387 Fungi, 367, 385, 387, 404, 437 G Gait, 267, 387 Gallbladder, 359, 379, 387 Gametogenesis, 51, 387 Ganglia, 359, 366, 387, 408, 414, 430 Gas, 362, 370, 387, 393, 409, 420, 423, 435 Gas exchange, 387, 420, 423, 435 Gastric, 157, 370, 383, 387, 392 Gastrin, 387, 393 Gastroenterology, 70, 144, 228, 387 Gastrointestinal, 271, 368, 383, 388, 402, 426, 427, 429 Gastrostomy, 197, 388 Gelatin, 388, 389, 432 Gene Deletion, 104, 135, 140, 142, 218, 388 Gene Duplication, 51, 388 Gene Expression Profiling, 49, 388 Gene Rearrangement, 19, 214, 388 Gene Silencing, 10, 388 Gene Targeting, 15, 49, 61, 388 Genetic Code, 388, 410 Genetic Counseling, 54, 79, 85, 164, 269, 388 Genetic Engineering, 367, 374, 388 Genetic testing, 269, 293, 388, 417 Genetic transcription, 388, 419, 433 Genital, 373, 389, 397 Genomics, 23, 25, 158, 159, 186, 217, 220, 240, 243, 244, 297, 389 Genotype, 15, 18, 21, 64, 69, 85, 104, 144, 146, 161, 162, 177, 199, 272, 389, 415 Germ Cells, 389, 403, 427, 431 Germ-Line Mutation, 8, 389 Gestation, 389, 416 Gland, 53, 377, 389, 401, 412, 416, 419, 425, 429, 430, 432 Glucocorticoid, 389, 418 Glucose, 26, 56, 115, 247, 272, 279, 379, 389, 391, 396, 415, 424 Glucuronic Acid, 389, 392 Glutamate, 246, 384, 389 Glutamic Acid, 389, 409, 419
Index 445
Glutamine, 62, 175, 205, 267, 269, 389 Glutathione Peroxidase, 254, 259, 389, 425 Glycine, 362, 389, 409, 426 Glycogen, 306, 389, 415 Glycogen Storage Disease, 306, 389 Glycosaminoglycans, 384, 390, 420 Glycosylation, 31, 133, 193, 390 Goblet Cells, 382, 390 Gonadal, 390, 429 Gonads, 390, 394 Gout, 109, 374, 390 Governing Board, 390, 418 Gp120, 390, 414 Graft, 34, 286, 295, 390, 393 Graft Survival, 34, 390 Grafting, 276, 390, 395 Granulocytes, 390, 407, 426, 437 Gravis, 151, 303, 390 Growth factors, 62, 73, 95, 286, 292, 295, 390, 404 Guanine, 48, 390, 421 Guanylate Cyclase, 390, 409 H Hammer, 291, 390, 411 Haptens, 360, 390 Headache, 390, 417 Heart attack, 370, 391 Heart failure, 54, 114, 128, 391 Heartbeat, 391, 430, 436 Heat-Shock Proteins, 391, 405 Heat-Shock Proteins 90, 391, 405 Hematopoietic Stem Cells, 78, 296, 391 Heme, 378, 391, 407 Hemidesmosomes, 55, 391 Hemochromatosis, 94, 391 Hemoglobin, 362, 384, 391, 399, 428, 431 Hemoglobinopathies, 388, 391 Hemolysis, 384, 391 Hemolytic, 163, 391, 431 Hemophilia, 51, 391 Hemorrhage, 236, 390, 391, 430 Hemostasis, 235, 391, 396, 426 Heparan Sulfate Proteoglycan, 118, 392 Heparin, 139, 392 Heparin-binding, 139, 392 Hepatic, 94, 392, 400 Hepatocyte, 73, 392 Hepatocyte Growth Factor, 73, 392 Hepatoma, 35, 392 Heredity, 149, 179, 182, 222, 269, 388, 389, 392 Herpetiformis, 16, 392
Heterochromatin, 10, 38, 392 Heterodimers, 392, 396, 433 Heterogeneity, 23, 42, 45, 56, 65, 96, 159, 160, 161, 164, 169, 196, 360, 392 Heterogenic, 392 Heterogenous, 59, 291, 392 Heterozygotes, 176, 380, 392 Histamine, 99, 362, 392 Histidine, 392 Histology, 7, 30, 87, 392, 413 Holidays, 344, 392 Homeostasis, 27, 40, 60, 77, 94, 198, 246, 392, 427 Homeotic, 15, 392 Homodimer, 28, 392, 433 Homogenate, 285, 393 Homogeneous, 376, 393 Homologous, 40, 51, 361, 377, 388, 392, 393, 407, 425, 430 Hormonal, 365, 377, 393 Horny layer, 383, 393 Host, 20, 21, 29, 40, 44, 74, 83, 84, 286, 290, 295, 366, 390, 393, 436 Humeral, 148, 221, 243, 340, 393 Humoral, 21, 393 Humour, 393 Hybrid, 16, 29, 44, 57, 103, 374, 393 Hybridization, 22, 91, 278, 371, 393, 410 Hydrogen, 359, 361, 366, 369, 379, 384, 389, 393, 400, 405, 409, 410, 412, 415, 420 Hydrogen Peroxide, 389, 393, 400 Hydrolysis, 26, 62, 359, 393, 415, 420 Hydrops Fetalis, 100, 393 Hydroxylysine, 374, 393 Hydroxyproline, 362, 374, 393 Hyperphagia, 345, 393 Hyperplasia, 75, 393 Hypertension, 19, 103, 370, 394, 397 Hyperthermia, 185, 356, 391, 394 Hypertrophic cardiomyopathy, 120, 394 Hypertrophy, 70, 75, 87, 93, 130, 173, 206, 277, 393, 394 Hyperuricemia, 390, 394 Hypogonadism, 278, 345, 394 Hypoplasia, 131, 279, 394, 418 Hypotensive, 226, 394 Hypothalamus, 365, 368, 394, 416 Hypotonia, 282, 345, 356, 394 Hypoventilation, 132, 394 I Ichthyosis, 139, 394 Ichthyosis Vulgaris, 139, 394
446 Muscular Dystrophy
Id, 251, 260, 338, 352, 354, 394 Iliac Artery, 385, 394, 434 Immune function, 394, 433 Immune response, 8, 21, 31, 50, 73, 99, 169, 363, 365, 377, 390, 394, 436 Immune system, 34, 53, 71, 72, 367, 394, 395, 401, 406, 407, 415, 435, 437 Immunity, 8, 99, 394 Immunofluorescence, 93, 394 Immunoglobulin, 6, 363, 394, 405 Immunohistochemistry, 95, 129, 394 Immunologic, 271, 372, 395, 422 Immunology, 21, 29, 50, 64, 70, 360, 395 Impairment, 113, 170, 171, 179, 180, 339, 364, 385, 395, 403 Implant radiation, 395, 397, 398, 421, 437 Implantation, 37, 53, 375, 395, 412 In situ, 75, 96, 165, 171, 278, 395 In Situ Hybridization, 165, 278, 395 Incision, 395, 397 Indicative, 281, 300, 395, 413, 435 Induction, 58, 67, 74, 76, 104, 395 Infancy, 297, 345, 395 Infant Mortality, 342, 395 Infant, Newborn, 360, 395 Infarction, 372, 377, 395, 404 Inflammation, 53, 226, 363, 374, 385, 386, 395, 407, 416, 424, 431 Inflammatory bowel disease, 5, 395 Infusion, 298, 395 Initiation, 23, 396, 411, 419, 422, 433 Inlay, 396, 423 Innervation, 41, 56, 95, 385, 396, 411, 420 Insecticides, 396, 437 Insertional, 51, 396 Insight, 7, 19, 24, 39, 43, 46, 59, 66, 78, 85, 94, 102, 396 Insulator, 396, 406 Insulin, 56, 73, 174, 271, 272, 286, 295, 396 Insulin-dependent diabetes mellitus, 396 Insulin-like, 73, 174, 271, 396 Integrins, 14, 27, 76, 85, 174, 276, 391, 396 Intercellular Junctions, 47, 396 Interferon, 21, 396 Interferon-alpha, 396 Intermediate Filament Proteins, 80, 396 Intermediate Filaments, 4, 18, 391, 397 Intermittent, 218, 397 Internal Medicine, 70, 229, 387, 397 Internal radiation, 397, 398, 421, 437 Interphase, 392, 397 Interstitial, 368, 384, 397, 398, 403, 437
Intestinal, 94, 174, 347, 370, 382, 383, 397, 413 Intestine, 368, 397, 399 Intoxication, 397, 437 Intracellular Membranes, 397, 403 Intracranial Hypertension, 390, 397, 413 Intramuscular, 8, 208, 397 Intraperitoneal, 247, 397 Intravascular, 46, 397 Intravenous, 52, 124, 236, 395, 397 Intrinsic, 37, 105, 360, 366, 397 Introns, 91, 132, 397, 420 Intubation, 174, 220, 370, 397 Invasive, 13, 205, 293, 394, 397, 401 Invertebrates, 53, 91, 154, 397 Involuntary, 366, 385, 397, 407, 422, 427, 432 Involution, 53, 397 Iodine, 113, 398 Ion Channels, 38, 85, 364, 398 Ionizing, 383, 398, 421 Ions, 359, 366, 369, 380, 381, 393, 398, 403, 405, 418, 427 Irradiation, 286, 294, 295, 398, 437 Ischemia, 107, 156, 365, 398 Isoenzyme, 377, 398 Isolated limb perfusion, 99, 398 Isometric Contraction, 22, 42, 62, 270, 398 J Joint, 147, 189, 207, 235, 282, 364, 398, 401, 411, 430, 431 K Kb, 8, 10, 38, 116, 151, 173, 182, 287, 288, 297, 322, 398 Keratin, 18, 398 Keratinocytes, 55, 398 Keto, 399, 433 Kidney Disease, 83, 273, 322, 399 Kinetics, 135, 399 L Labile, 374, 399 Lacrimal, 385, 399, 411 Language Development, 18, 294, 399 Language Disorders, 77, 399 Large Intestine, 379, 397, 399, 422, 427 Latent, 15, 399 Lectin, 399, 403 Lens, 191, 370, 376, 399, 423, 437 Leprosy, 52, 399 Lethal, 25, 30, 41, 48, 72, 91, 99, 102, 178, 296, 298, 399 Leucine, 76, 249, 399
Index 447
Leukemia, 19, 139, 172, 388, 399 Leukocytes, 368, 372, 383, 390, 396, 399, 434 Library Services, 352, 399 Life Expectancy, 229, 399 Ligament, 399, 419 Ligands, 31, 39, 53, 76, 292, 371, 396, 399 Ligase, 9, 181, 400 Limb perfusion, 400 Linkage Disequilibrium, 17, 218, 400 Lipid, 84, 264, 371, 373, 396, 399, 400, 403, 406, 412 Lipid Peroxidation, 400, 412 Lipodystrophy, 5, 80, 83, 143, 149, 176, 213, 400 Lipoprotein, 400, 436 Liver Regeneration, 47, 400 Liver scan, 400, 424 Lobe, 362, 363, 372, 400 Localized, 10, 26, 36, 54, 56, 144, 248, 282, 379, 381, 386, 395, 399, 400, 416 Locomotion, 400, 416 Locomotor, 294, 400 Longitudinal Studies, 81, 400 Longitudinal study, 18, 128, 208, 400 Loop, 18, 401, 407 Lucida, 399, 401 Luciferase, 6, 95, 104, 401 Lumbar, 207, 401 Lumen, 40, 401 Lupus, 401, 431 Luxation, 380, 401 Lymph, 35, 365, 372, 377, 382, 393, 401, 430 Lymph node, 35, 365, 372, 401 Lymphatic, 382, 395, 401, 404, 427 Lymphatic system, 401, 427 Lymphocyte, 363, 401, 403 Lymphoid, 73, 363, 401 Lymphoma, 197, 401 Lysosome, 26, 401 M Macrophage, 286, 295, 401 Macrophage Colony-Stimulating Factor, 286, 295, 401 Magnetic Resonance Spectroscopy, 122, 217, 249, 258, 402 Magnetoencephalography, 88, 402 Malaria, 40, 402 Malaria, Falciparum, 402 Malaria, Vivax, 402 Malformation, 23, 402
Malignancy, 103, 402 Malignant, 35, 139, 185, 402, 418, 421, 424 Malignant tumor, 402, 418, 424 Malnutrition, 209, 365, 369, 402, 406 Mammary, 53, 402 Mammography, 35, 402 Mandible, 4, 373, 402, 423 Manifest, 7, 278, 365, 402 Masseter Muscle, 4, 402 Mastication, 402 Masticatory, 3, 402 Maxillary, 4, 403 Mechanical ventilation, 173, 260, 341, 369, 403 Mediate, 19, 27, 39, 40, 56, 66, 74, 77, 101, 105, 363, 371, 403, 405 Mediator, 61, 87, 403, 426 MEDLINE, 323, 403 Meiosis, 403, 430, 431 Melanin, 403, 415, 434 Membrane Fluidity, 279, 403 Membrane Fusion, 40, 403 Membrane Glycoproteins, 403 Membrane Potentials, 250, 403 Membrane Proteins, 14, 33, 38, 264, 279, 371, 403 Memory, 18, 85, 223, 265, 379, 403 Meninges, 372, 403, 428 Mental deficiency, 385, 403 Mental Disorders, 273, 403, 420 Mental Retardation, 77, 78, 105, 130, 131, 146, 186, 187, 235, 278, 279, 283, 344, 347, 403 Mesenchymal, 52, 53, 60, 62, 383, 401, 404 Mesoderm, 404, 434 Metabolic disorder, 26, 389, 390, 404 Metastasis, 18, 53, 91, 371, 404 Metastatic, 20, 50, 52, 247, 255, 404, 425 Metastatic cancer, 20, 52, 404 Methyltransferase, 38, 84, 404 MI, 21, 22, 28, 49, 83, 96, 171, 358, 404 Mice Minute Virus, 404, 413 Mice, Transgenic, 34, 404 Microbe, 404, 433 Microbiology, 70, 95, 360, 365, 404 Microfilaments, 18, 397, 404 Microglia, 364, 404 Microorganism, 374, 404, 413, 437 Microscopy, 25, 55, 80, 82, 93, 103, 135, 169, 175, 186, 222, 366, 404 Microtubule-Associated Proteins, 18, 404 Microtubules, 18, 397, 404
448 Muscular Dystrophy
Midwifery, 299, 404 Migration, 11, 18, 34, 37, 52, 60, 78, 113, 190, 276, 295, 405 Milliliter, 368, 405 Mineralization, 81, 405 Mitochondria, 14, 77, 246, 259, 372, 405, 411 Mitosis, 65, 364, 405 Mitotic, 24, 37, 65, 81, 133, 405, 436 Mobility, 80, 339, 343, 405 Modeling, 86, 192, 405 Modification, 8, 21, 63, 362, 388, 405, 421 Modulator, 87, 103, 405 Molecular Chaperones, 11, 86, 372, 391, 405 Molecular Structure, 63, 405 Monitor, 5, 48, 142, 267, 270, 377, 405, 409 Monoclonal, 66, 90, 398, 405, 421, 437 Monoclonal antibodies, 66, 90, 405 Monocyte, 401, 405 Monogenic, 136, 405 Mononuclear, 401, 405, 434 Morphogenesis, 48, 63, 107, 385, 406 Morphological, 58, 89, 189, 204, 280, 283, 360, 382, 406 Morphology, 3, 48, 290, 370, 391, 406 Motility, 63, 75, 103, 147, 406, 426 Motor Activity, 376, 406, 421 Motor nerve, 56, 88, 343, 385, 406, 414 Motor Neurons, 346, 406 Motor Skills, 178, 406 Mucins, 383, 390, 406 Mucosa, 382, 401, 406 Multiple sclerosis, 21, 77, 95, 104, 304, 305, 339, 406 Muscle Contraction, 45, 381, 406, 408 Muscle Hypertonia, 406, 408 Muscle Hypotonia, 282, 406 Muscle Proteins, 36, 87, 296, 406 Muscle relaxant, 236, 406 Muscle Relaxation, 406, 407 Muscle tension, 406 Muscular Atrophy, 21, 121, 153, 173, 180, 185, 190, 208, 211, 214, 216, 289, 297, 334, 343, 406 Muscular Diseases, 29, 406, 408, 413, 421 Musculature, 3, 407 Musculoskeletal System, 52, 407, 411 Music Therapy, 254, 407 Mutagenic, 19, 407 Mutagens, 387, 407 Mutate, 48, 407
Myasthenia, 47, 151, 303, 407 Myelin, 21, 58, 406, 407 Myeloid Cells, 73, 407 Myocardium, 55, 239, 404, 407 Myofibrils, 83, 93, 96, 369, 381, 407 Myogenic Regulatory Factors, 407 Myogenin, 50, 407 Myoglobin, 306, 357, 407 Myosin, 74, 93, 103, 141, 217, 359, 406, 407, 434 Myositis, 119, 407 Myotonia, 17, 64, 72, 278, 279, 289, 293, 306, 407 N Naive, 60, 268, 269, 407 Natural selection, 367, 407 NCI, 1, 271, 272, 321, 373, 407 Need, 3, 4, 9, 49, 60, 77, 105, 173, 244, 299, 301, 305, 348, 360, 373, 389, 401, 408 Needle biopsy, 270, 386, 408 Neonatal, 31, 47, 56, 194, 196, 248, 279, 282, 395, 408 Neonatal period, 279, 408 Neoplastic, 401, 408 Nephropathy, 399, 408 Nerve Regeneration, 53, 58, 408 Nervous System, 11, 18, 47, 48, 52, 76, 78, 95, 104, 122, 142, 164, 183, 187, 201, 283, 284, 292, 294, 359, 360, 365, 366, 368, 372, 381, 387, 389, 390, 403, 404, 406, 408, 409, 411, 414, 417, 426, 430 Networks, 58, 91, 240, 347, 408 Neural, 5, 23, 41, 47, 85, 240, 360, 382, 393, 404, 408, 427 Neural tube defects, 23, 408 Neurodegenerative Diseases, 77, 366, 408 Neurogenic, 194, 239, 408 Neurologic, 56, 382, 408 Neurologist, 62, 408 Neuromuscular Blocking Agents, 365, 408 Neuromuscular Diseases, 47, 62, 77, 259, 301, 342, 343, 408, 413, 421 Neuromuscular Junction, 27, 41, 47, 56, 88, 89, 265, 292, 359, 408, 409, 411, 423 Neuronal, 11, 38, 48, 56, 91, 95, 107, 113, 149, 156, 190, 195, 409 Neurons, 5, 47, 81, 91, 154, 155, 247, 379, 384, 387, 406, 409, 430 Neuropathy, 58, 84, 119, 140, 362, 409, 414 Neuropeptides, 369, 409 Neurophysiology, 5, 132, 220, 249, 379, 409
Index 449
Neurosciences, 95, 104, 232, 409 Neurotoxic, 364, 409 Neurotransmitter, 359, 360, 362, 368, 371, 389, 392, 398, 409, 426 Neutrons, 398, 409, 421 Niacin, 409, 434 Nitric Oxide, 9, 38, 54, 56, 61, 73, 107, 111, 115, 149, 156, 195, 234, 265, 409 Nitrogen, 361, 384, 386, 389, 409, 434 Nuclear Envelope, 5, 33, 80, 84, 101, 184, 233, 234, 409 Nuclear Pore, 20, 409 Nuclear Proteins, 40, 163, 410 Nuclei, 43, 66, 67, 88, 90, 107, 183, 237, 362, 363, 388, 397, 402, 405, 409, 410, 411, 420 Nucleic acid, 51, 283, 287, 288, 290, 291, 366, 369, 388, 393, 395, 407, 409, 410, 418, 421 Nucleic Acid Hybridization, 393, 410 Nucleic Acid Probes, 291, 410 Nucleoproteins, 410 Nursing Staff, 47, 410 Nutritional Support, 388, 410 O Obsessive-Compulsive Disorder, 77, 410 Occupational Therapy, 307, 410 Ocular, 203, 257, 340, 410, 411 Ointments, 410, 413 Oncogene, 392, 410 Oncogenic, 98, 126, 396, 410 Oncology, 47, 139, 247, 255, 410 On-line, 19, 355, 410 Oogenesis, 66, 162, 205, 410 Opacity, 370, 379, 410 Operon, 411, 419, 423 Ophthalmology, 104, 115, 146, 221, 386, 411 Ophthalmoplegia, 131, 203, 411 Opsin, 411, 423, 424 Optic Nerve, 411, 423 Orbicularis, 4, 411 Organ Culture, 41, 411, 432 Organelles, 40, 378, 411, 416 Ori region, 411, 422 Orofacial, 3, 411 Orthopaedic, 81, 121, 128, 165, 226, 241, 309, 411 Osmosis, 411 Osmotic, 83, 411 Ossicles, 390, 411 Ossification, 411, 412 Osteoarthritis, 5, 249, 411
Osteoclasts, 27, 411 Osteogenesis, 300, 346, 412 Osteoporosis, 27, 81, 249, 412, 418 Ostomy, 347, 412 Ovaries, 345, 412, 426, 431 Ovulation, 66, 412 Ovum, 378, 389, 412, 419, 434, 437, 438 Ovum Implantation, 412, 434 Oxandrolone, 268, 269, 412 Oxidation, 247, 359, 364, 378, 389, 400, 412 Oxidative Phosphorylation, 246, 259, 264, 412 Oxidative Stress, 150, 412 Oxygen Consumption, 412, 423 Oxygenation, 197, 412 P Pacemaker, 128, 412 Palate, 4, 48, 373, 412 Palliative, 186, 412, 432 Palsy, 81, 412 Pancreas, 359, 379, 387, 391, 396, 412, 425 Pancreatic, 370, 412 Paneth Cells, 383, 413 Paraffin, 170, 206, 248, 258, 413 Paralysis, 95, 306, 339, 367, 369, 377, 411, 413, 417, 420, 421, 427, 431 Paraparesis, 23, 413 Paraplegia, 339, 413 Paresthesia, 413, 431 Parturition, 85, 413 Parvovirus, 194, 404, 413 Patch, 48, 63, 95, 413 Pathogen, 21, 413 Pathologic, 80, 84, 124, 181, 364, 367, 368, 377, 413, 423, 428 Pathologic Processes, 364, 413 Pathologies, 24, 38, 56, 64, 413 Pathologist, 413 Pathophysiology, 43, 54, 55, 60, 64, 67, 68, 93, 169, 189, 207, 249, 266, 413 Patient Advocacy, 341, 345, 413 Patient Education, 337, 340, 350, 352, 358, 413 Pedigree, 79, 240, 413 Pelvic, 189, 207, 280, 282, 413, 419 Pelvis, 394, 401, 412, 413, 435 Pemphigus, 16, 359, 413 Penicillamine, 247, 248, 413 Penicillin, 414, 435 Peptide, 6, 27, 39, 53, 57, 62, 70, 95, 209, 362, 386, 398, 414, 416, 419, 420 Peptide T, 95, 414
450 Muscular Dystrophy
Perception, 74, 376, 414, 424 Percutaneous, 197, 414 Perfusion, 5, 178, 414 Pericardium, 414, 431 Peripheral blood, 22, 271, 396, 414 Peripheral Nervous System, 131, 269, 408, 409, 412, 413, 414, 421 Peripheral Nervous System Diseases, 408, 413, 414, 421 Peripheral Neuropathy, 57, 77, 84, 414 Peripheral Vascular Disease, 5, 414 Peritoneal, 397, 414 Peritoneal Cavity, 397, 414 Petrolatum, 382, 414 Petroleum, 413, 414 PH, 38, 89, 174, 230, 368, 415 Phagocyte, 401, 415 Phallic, 386, 415 Pharmacologic, 249, 362, 415, 433 Pharynx, 179, 415 Phenolphthalein, 382, 415 Phenylalanine, 415, 434 Pheromone, 63, 415 Phospholipases, 415, 426 Phospholipids, 385, 400, 403, 415 Phosphorus, 122, 369, 415 Phosphorylase, 369, 415 Phosphorylated, 24, 87, 374, 415 Phosphorylation, 24, 41, 66, 76, 86, 106, 279, 290, 415 Photoreceptor, 15, 220, 415, 424 Physical Therapy, 254, 256, 258, 304, 307, 309, 335, 415 Physiologic, 20, 360, 385, 415, 422, 423 Pigments, 370, 416, 423 Pilot study, 254, 268, 416 Pituitary Gland, 377, 386, 416 Placenta, 276, 416, 418, 434 Plants, 361, 365, 366, 369, 370, 373, 389, 399, 406, 416, 424, 433 Plasma cells, 363, 416 Plasmid, 46, 416, 435 Plasticity, 78, 100, 416 Plastids, 372, 411, 416 Platelet Activation, 416, 426 Platelet Aggregation, 362, 409, 416 Platelet-Derived Growth Factor, 286, 295, 416 Platelets, 369, 409, 416, 426 Platinum, 401, 416 Pleated, 398, 416 Pneumonia, 258, 376, 416
Point Mutation, 102, 104, 153, 167, 205, 416 Poliomyelitis, 304, 305, 341, 417 Polycystic, 83, 417 Polymerase, 24, 135, 188, 278, 417, 419, 422 Polymerase Chain Reaction, 135, 188, 278, 417 Polymers, 4, 57, 417, 420 Polymorphic, 38, 42, 125, 373, 417 Polymorphism, 157, 161, 209, 240, 278, 417 Polysaccharide, 363, 417, 420 Port, 6, 417 Port-a-cath, 417 Posterior, 4, 293, 362, 365, 372, 373, 380, 411, 412, 417 Postmenopausal, 412, 417 Postnatal, 15, 81, 385, 417, 429 Postsynaptic, 56, 76, 89, 106, 417, 426 Post-synaptic, 56, 417 Post-translational, 84, 417 Potassium, 38, 85, 95, 149, 279, 306, 403, 417, 418 Potassium Channels, 38, 85, 418 Potentiation, 418, 426 Practice Guidelines, 324, 418 Practice Management, 200, 418 Preclinical, 111, 237, 418 Precursor, 34, 84, 91, 298, 373, 381, 383, 415, 418, 433, 434, 435 Prednisolone, 184, 210, 218, 249, 418 Prednisone, 103, 110, 142, 164, 210, 271, 306, 418 Prenatal, 79, 86, 125, 153, 161, 171, 177, 188, 207, 210, 211, 276, 294, 358, 382, 385, 418 Pressoreceptors, 366, 418 Presynaptic, 47, 56, 409, 418 Prevalence, 3, 31, 82, 153, 211, 278, 345, 418 Prickle, 359, 398, 418 Prion, 77, 418 Probe, 6, 69, 278, 282, 283, 287, 288, 418 Progeny, 51, 389, 418 Progeria, 84, 418 Progesterone, 418, 429 Progressive disease, 286, 295, 419 Proline, 39, 374, 393, 419 Promoter, 6, 8, 48, 71, 88, 96, 106, 108, 233, 293, 297, 419 Promotor, 95, 419 Prone, 19, 253, 419 Prone Position, 253, 419
Index 451
Prophase, 419, 430 Prophylaxis, 258, 419 Prospective study, 136, 400, 419 Prostate, 35, 419 Protease, 32, 49, 419 Protein Binding, 101, 419 Protein C, 7, 12, 14, 17, 50, 54, 59, 60, 61, 67, 70, 130, 143, 241, 276, 283, 294, 359, 361, 362, 366, 374, 385, 398, 400, 406, 419, 428, 434, 435, 436 Protein Conformation, 362, 398, 419 Protein Folding, 6, 86, 419 Protein Isoforms, 361, 419 Protein Kinases, 290, 419 Protein S, 16, 23, 86, 102, 304, 367, 388, 419, 420, 424, 431 Proteoglycan, 76, 265, 276, 420 Proteolytic, 9, 28, 84, 375, 386, 420 Protocol, 28, 62, 231, 315, 420 Protons, 393, 398, 402, 420, 421 Protozoa, 367, 404, 420 Protozoan, 402, 420 Proximal, 10, 17, 42, 48, 64, 177, 287, 291, 358, 380, 418, 420 Pseudogenes, 51, 420 Psychiatry, 120, 235, 250, 257, 386, 420, 435 Psychic, 403, 420 Psychoactive, 420, 437 Psychological Tests, 269, 420 Ptosis, 131, 164, 420 Public Policy, 323, 420 Pulmonary, 103, 132, 211, 213, 214, 258, 361, 367, 369, 383, 394, 420, 421, 435, 436 Pulmonary Alveoli, 394, 420 Pulmonary Artery, 367, 420, 436 Pulmonary Valve, 213, 421 Pulsation, 386, 421 Pulse, 214, 405, 421 Purines, 366, 421, 426 Pustular, 392, 421 Pyrimidines, 366, 421, 426 Q Quadriplegia, 339, 421 Quality of Life, 22, 62, 102, 113, 136, 219, 294, 301, 340, 342, 421 Quaternary, 419, 421 Quiescent, 7, 65, 73, 421 R Race, 310, 361, 405, 421 Racemic, 361, 421 Radiation, 365, 382, 383, 384, 386, 387, 394, 397, 398, 421, 424, 437
Radiation therapy, 384, 397, 398, 421, 437 Radioactive, 246, 365, 368, 393, 395, 397, 398, 400, 405, 409, 410, 421, 424, 437 Radiolabeled, 398, 421, 437 Radiological, 414, 421 Radiotherapy, 368, 398, 421, 437 Randomized, 52, 110, 112, 267, 270, 271, 381, 422 Reagent, 283, 401, 422 Recessive gene, 282, 287, 288, 422 Recombinant, 7, 12, 13, 25, 30, 34, 58, 59, 60, 65, 72, 75, 90, 95, 99, 217, 290, 295, 422, 435 Recombinant Proteins, 60, 90, 422 Recombination, 40, 51, 388, 422 Rectum, 364, 368, 374, 379, 387, 395, 399, 419, 422 Recurrence, 85, 166, 422 Red blood cells, 279, 384, 391, 422, 424, 428 Red Nucleus, 365, 422 Reentry, 119, 176, 422 Refer, 1, 374, 386, 387, 400, 407, 409, 410, 422, 433 Reflex, 385, 422 Refraction, 422, 428 Refractory, 28, 422 Regeneration, 31, 34, 47, 50, 57, 61, 73, 75, 87, 88, 93, 119, 276, 286, 295, 296, 305, 361, 386, 422 Regimen, 256, 381, 422 Relaxant, 422 Remission, 218, 422 Replication Origin, 186, 422 Repressor, 33, 91, 411, 422 Reproductive cells, 387, 389, 423 Resolving, 343, 423 Resorption, 412, 423 Respiration, 85, 222, 370, 378, 405, 423 Respirator, 403, 423, 436 Respiratory distress syndrome, 47, 369, 423 Respiratory failure, 82, 116, 291, 294, 423, 436 Respiratory Paralysis, 364, 423 Respiratory Physiology, 423, 435 Restoration, 59, 220, 248, 265, 280, 415, 423, 437 Retina, 15, 182, 373, 381, 399, 411, 423, 424, 437 Retinal, 15, 65, 205, 220, 241, 271, 376, 411, 423, 424
452 Muscular Dystrophy
Retinoblastoma, 50, 423 Retinol, 423, 424 Retrograde, 220, 397, 423 Retrospective, 145, 297, 423 Retroviral vector, 220, 388, 423 Rhabdomyosarcoma, 139, 247, 255, 424 Rheumatism, 305, 424 Rhodopsin, 411, 423, 424 Ribosome, 424, 434 Rigidity, 168, 192, 416, 424 Risk factor, 419, 424 Rod, 8, 265, 284, 366, 373, 415, 424 S Salivary, 379, 385, 424, 430 Salivary glands, 379, 385, 424 Saponins, 424, 429 Sarcolemma, 34, 54, 59, 93, 96, 196, 277, 280, 281, 424 Sarcomere, 36, 54, 82, 96, 257, 424 Satellite, 37, 50, 60, 62, 69, 93, 227, 298, 424 Saturate, 48, 424 Scans, 269, 424 Schizoid, 424, 437 Schizophrenia, 77, 424, 437 Schizotypal Personality Disorder, 424, 437 Scleroproteins, 398, 424 Sclerosis, 5, 20, 47, 77, 83, 301, 334, 406, 425 Scoliosis, 124, 135, 207, 211, 222, 235, 335, 336, 346, 425 Screening, 35, 57, 134, 161, 194, 195, 196, 207, 222, 268, 276, 280, 374, 425 Scrotum, 425, 431 Secondary tumor, 404, 425 Secretion, 377, 380, 383, 392, 393, 396, 404, 406, 425, 433 Secretory, 40, 425 Secretory Vesicles, 40, 425 Sedimentation, 425, 434 Segregation, 422, 425 Selenium, 248, 249, 250, 254, 259, 425, 427 Selenomethionine, 254, 425 Self Care, 359, 425 Self-Help Groups, 300, 345, 425 Semen, 419, 425 Senescence, 93, 418, 425 Senile, 94, 412, 425 Sensibility, 362, 425 Sensor, 85, 425 Sepsis, 55, 425 Sequence Analysis, 104, 426 Sequence Homology, 88, 414, 426
Sequencing, 69, 70, 417, 426 Sequester, 72, 200, 426 Serine, 290, 426 Serotonin, 409, 426, 434 Serous, 382, 383, 393, 426 Sex Characteristics, 360, 426 Shock, 6, 87, 372, 426, 434 Side effect, 287, 360, 367, 394, 426, 433 Signal Transduction, 9, 13, 20, 26, 27, 69, 77, 95, 101, 104, 371, 391, 426 Skeleton, 15, 81, 93, 284, 359, 385, 398, 426, 427 Skull, 382, 408, 427, 431 Small intestine, 393, 397, 427, 436 Smooth muscle, 9, 32, 61, 92, 103, 121, 279, 362, 369, 376, 392, 406, 427 Social Environment, 421, 427 Sodium, 38, 254, 264, 279, 290, 390, 403, 427 Sodium Channels, 38, 290, 427 Sodium Selenite, 254, 427 Soft tissue, 368, 411, 426, 427 Solid tumor, 363, 427 Solitary Nucleus, 365, 427 Solvent, 411, 427 Soma, 427 Somatic, 51, 99, 133, 162, 167, 360, 371, 382, 389, 393, 403, 405, 414, 427 Somatic cells, 51, 371, 389, 403, 405, 427 Sound wave, 376, 427 Spasm, 408, 427 Spastic, 23, 427 Spasticity, 427 Specialist, 6, 344, 348, 428 Species, 9, 60, 67, 74, 280, 361, 366, 372, 374, 377, 379, 383, 392, 393, 402, 403, 404, 405, 413, 415, 421, 426, 428, 430, 434, 436, 437, 438 Specific immune cells, 73, 428 Specificity, 27, 31, 39, 40, 43, 53, 62, 66, 74, 91, 104, 223, 285, 360, 428 Spectrin, 99, 259, 381, 428 Spectrometer, 6, 428 Spectroscopic, 25, 402, 428 Spectrum, 17, 69, 79, 123, 128, 404, 428 Speech pathologist, 306, 307, 428 Sperm, 133, 373, 423, 428, 431, 434 Spermatogenesis, 205, 428 Spherocytes, 428 Spherocytosis, 100, 428 Sphincter, 239, 428 Spina bifida, 338, 339, 408, 428
Index 453
Spinal cord, 104, 269, 364, 368, 372, 373, 403, 408, 409, 413, 414, 421, 422, 423, 428, 430 Spinal Cord Diseases, 413, 421, 423, 428 Spinal Injuries, 346, 428 Spinal Nerves, 414, 428 Spinous, 383, 398, 429 Spirometry, 126, 429 Sporadic, 116, 161, 173, 408, 423, 429 Stabilization, 25, 56, 58, 85, 226, 429 Stabilizer, 268, 429 Staging, 424, 429 Statistically significant, 68, 227, 429 Steel, 373, 429 Stem cell transplantation, 60, 314, 429 Stem Cells, 7, 34, 37, 43, 44, 46, 53, 79, 81, 93, 100, 194, 298, 336, 429, 434 Stenosis, 213, 429, 430 Stent, 412, 429 Sterile, 48, 364, 429 Sterility, 24, 429 Steroid, 166, 268, 269, 377, 391, 424, 429 Stimulant, 392, 429, 435 Stimulus, 376, 380, 384, 396, 398, 422, 429, 432 Stoma, 412, 429 Stomach, 359, 379, 384, 387, 388, 393, 414, 415, 427, 429 Stool, 374, 399, 429 Strand, 51, 108, 417, 429 Stress, 5, 20, 71, 82, 83, 96, 110, 206, 255, 258, 281, 365, 372, 412, 429 Stricture, 429, 430 Stroke, 5, 47, 56, 77, 104, 128, 269, 270, 271, 273, 322, 334, 336, 337, 338, 339, 370, 430 Subacute, 395, 430 Subclinical, 201, 395, 430 Subcutaneous, 400, 418, 430 Submaxillary, 383, 430 Subspecies, 428, 430 Substrate, 51, 217, 220, 391, 430 Substrate Specificity, 217, 430 Sudden cardiac death, 55, 430 Sulfur, 384, 430 Supplementation, 249, 258, 259, 430 Support group, 340, 341, 342, 345, 358, 430 Suppression, 63, 377, 388, 430 Suppressive, 11, 430 Sympathetic Nervous System, 113, 365, 430 Symphysis, 373, 419, 430 Symptomatic, 152, 214, 289, 430
Synapse, 15, 41, 47, 56, 88, 360, 361, 409, 418, 430, 434 Synapsis, 430 Synaptic, 41, 47, 76, 88, 95, 361, 409, 426, 430 Synergistic, 21, 431, 432 Systemic disease, 394, 431 Systemic lupus erythematosus, 21, 431 Systolic, 117, 212, 243, 394, 431 T Tachycardia, 119, 241, 293, 431 Telencephalon, 366, 372, 431 Telomere, 148, 165, 431 Temporal, 45, 74, 77, 201, 362, 431 Terminator, 374, 431 Testicles, 36, 425, 431 Testicular, 279, 431 Testis, 390, 431 Tetracycline, 31, 431 Tetrodotoxin, 246, 431 Thalamic, 231, 365, 431 Thalamic Diseases, 365, 431 Thalassemia, 24, 431 Therapeutics, 13, 65, 73, 102, 189, 249, 432 Thermal, 100, 380, 391, 409, 417, 432 Thigh, 189, 385, 432 Thoracic, 222, 379, 432, 437 Thorax, 117, 138, 170, 201, 401, 432 Threonine, 290, 414, 426, 432 Threshold, 10, 71, 394, 432 Thrombin, 385, 416, 419, 432 Thrombomodulin, 419, 432 Thrombosis, 235, 396, 420, 430, 432 Thyroid, 35, 305, 398, 432, 434 Tic, 287, 288, 432 Tidal Volume, 114, 432 Tin, 413, 414, 416, 432 Tissue Culture, 69, 79, 432, 436 Tomography, 375, 402, 424, 432 Tone, 61, 103, 394, 406, 427, 432 Tonic, 85, 265, 432 Tonicity, 381, 391, 432 Tonus, 4, 432 Tooth Preparation, 359, 433 Topical, 393, 413, 414, 433 Torsion, 11, 395, 433 Tourniquet, 398, 400, 433 Toxic, iv, 72, 75, 94, 192, 365, 378, 381, 383, 394, 409, 425, 433 Toxicity, 8, 270, 433 Toxicology, 70, 324, 433 Toxin, 122, 228, 286, 294, 295, 382, 431, 433
454 Muscular Dystrophy
Toxoplasmosis, 40, 433 Trace element, 249, 427, 432, 433 Trachea, 415, 432, 433 Traction, 373, 433 Transaminases, 141, 433 Transcription Factors, 6, 60, 61, 71, 407, 433 Transduction, 7, 30, 51, 79, 101, 426, 433 Transfection, 104, 367, 388, 433 Transferases, 390, 433 Transforming Growth Factor beta, 144, 433 Transgenes, 13, 39, 58, 434 Translation, 20, 33, 65, 66, 67, 362, 420, 434 Translational, 33, 86, 129, 388, 434 Translocation, 51, 86, 287, 288, 373, 434 Transmitter, 56, 359, 364, 398, 403, 434 Transplantation, 37, 75, 79, 120, 125, 224, 229, 254, 285, 286, 294, 295, 315, 373, 434 Trauma, 47, 75, 172, 241, 366, 390, 431, 434 Trinucleotide Repeats, 105, 434 Trophic, 285, 286, 294, 295, 434 Trophoblast, 276, 367, 434 Tropomyosin, 103, 406, 434 Troponin, 103, 127, 237, 406, 434 Tryptophan, 100, 374, 426, 434 Tubulin, 25, 404, 434 Tumor Necrosis Factor, 112, 434 Tyrosine, 76, 77, 290, 434 U Ubiquitin, 9, 181, 434 Umbilical Arteries, 434 Umbilical Cord, 298, 434 Umbilical cord blood, 298, 434 Unconscious, 362, 378, 394, 434 Urea, 100, 435 Ureters, 435 Urethra, 419, 435 Uric, 390, 394, 421, 435 Urinary, 239, 250, 270, 347, 369, 435 Urinary tract, 270, 435 Urine, 269, 270, 306, 357, 367, 377, 383, 435 Uterus, 53, 372, 378, 382, 386, 387, 412, 419, 435 V Vaccine, 420, 435 Vacuole, 26, 435 Vagina, 372, 379, 435 Valine, 413, 435 Vascular, 32, 34, 61, 103, 121, 197, 205, 241, 366, 373, 382, 395, 409, 416, 418, 428, 435 Vascular Resistance, 366, 435
Vasoconstriction, 61, 383, 435 Vasodilator, 368, 392, 435 VE, 128, 164, 339, 435 Vector, 7, 8, 16, 21, 29, 30, 42, 50, 99, 100, 106, 114, 215, 396, 433, 435 Vein, 34, 270, 397, 409, 424, 434, 435 Venom, 364, 435 Venous, 372, 420, 435 Venous blood, 372, 435 Ventilation, 139, 170, 184, 197, 215, 217, 229, 236, 258, 341, 435, 436 Ventilator, 341, 403, 423, 436 Ventricle, 8, 362, 365, 394, 420, 421, 431, 436 Ventricular, 117, 119, 143, 148, 178, 212, 227, 241, 243, 253, 436 Ventricular Dysfunction, 148, 436 Ventricular fibrillation, 253, 436 Ventricular Function, 143, 178, 436 Venules, 368, 436 Vertebrae, 428, 436 Vertebral, 241, 242, 367, 428, 436 Vesicular, 392, 436 Veterinary Medicine, 323, 436 Villus, 356, 436 Vimentin, 98, 396, 436 Vinblastine, 434, 436 Vincristine, 434, 436 Vinculin, 57, 436 Viral, 7, 8, 20, 23, 29, 30, 49, 59, 71, 86, 265, 271, 369, 386, 410, 417, 433, 436 Viral vector, 7, 23, 30, 71, 436 Virion, 29, 30, 436 Virulence, 433, 436 Visceral, 365, 437 Visceral Afferents, 365, 437 Vital Capacity, 256, 437 Vitreous, 399, 423, 437 Vitreous Body, 423, 437 Vitro, 15, 16, 23, 25, 26, 29, 34, 37, 40, 41, 44, 48, 50, 55, 57, 75, 77, 82, 90, 96, 101, 104, 105, 133, 167, 172, 225, 246, 247, 259, 271, 285, 286, 294, 295, 371, 388, 392, 395, 417, 432, 437 Vivo, 5, 13, 15, 25, 29, 35, 39, 40, 41, 44, 48, 50, 51, 55, 57, 59, 61, 63, 75, 77, 81, 82, 87, 88, 90, 101, 105, 119, 217, 223, 249, 286, 295, 371, 388, 392, 395, 437 Voltage-gated, 290, 437 W Weight Gain, 385, 437
Index 455
White blood cell, 363, 399, 401, 405, 416, 437 Windpipe, 415, 432, 437 Withdrawal, 67, 437 Womb, 435, 437 Wound Healing, 53, 100, 371, 386, 396, 437 X Xenobiotics, 70, 437 Xenograft, 363, 437
X-ray, 24, 39, 99, 269, 270, 368, 375, 386, 398, 409, 421, 424, 429, 437 X-ray therapy, 398, 437 Y Yeasts, 387, 415, 437 Z Zebrafish, 218, 438 Zygote, 24, 376, 438 Zymogen, 419, 438
456 Muscular Dystrophy
