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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gov
